PMID- 1433482 TI - Mathematical description of the concentration of oxytetracycline and penicillin-G in tissue cages in calves as related to the serum concentration. AB - A mathematical model based on Fick's laws of diffusion describing the concentration of drug in tissue cage models was elaborated. The model takes into account differences in protein binding, tissue cage geometry and serum pharmacokinetics. The validity of the model was tested against experimental data obtained from a tissue cage model in calves by simultaneous fitting to serum and tissue cage fluid (TCF) data in a non-linear least-squares regression computer program. Concentrations of penicillin-G (pen-G) in serum and TCF following intravenous (i.v.) administration of potassium pen-G were adequately described by the mathematical model. Concentrations in TCF after intramuscular (i.m.) administration of the same drug and of procaine pen-G could be predicted by the mathematical model. Concentrations of oxytetracycline (OTC) in serum and TCF following i.v. administration and continuous i.v. infusions were also adequately described by the model, and TCF concentrations after i.m. administration of the same drug could be roughly predicted. The results indicate that pen-G and OTC have the same permeability coefficient for transport from serum to TCF. PMID- 1433483 TI - Pharmacokinetics of [3H]-ivermectin in the dog following oral administration of a beef-based chewable formulation containing ivermectin alone or in combination with pyrantel pamoate. PMID- 1433484 TI - Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin. AB - The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin concentrations in plasma, synovial fluid and urine were determined. Mean biological half-life of intravenously administered ampicillin and amoxicillin was 1.72 and 1.43 h respectively, whilst the distribution volume (Vss) appeared to be 0.180 and 0.192 1/kg. Orally administered pivampicillin and amoxicillin were rapidly absorbed. A maximum concentration in plasma of 3.80 micrograms/ml was reached 2 h after administration of pivampicillin to starved horses; in fed horses a maximum concentration of 5.12 micrograms/ml was reached 1 h after administration. After oral administration of amoxicillin a maximum concentration of 2.03 micrograms/ml was reached after 1 h. The (absolute) bioavailability of pivampicillin administered orally was 30.9% in starved horses and 35.9% in fed horses. The bioavailability of amoxicillin administered orally was 5.3% in starved horses. PMID- 1433485 TI - The pharmacokinetics and pharmacodynamics of furosemide in the anaesthetized dog. AB - The correlation between pharmacokinetics and dynamics of furosemide was investigated in anaesthetized dogs. After intravenous administration (i.v.) of furosemide (5 mg/kg), the plasma concentration declined rapidly with bioexponential decay. The half-life (t1/2 beta) of the late phase of elimination was 0.931 +/- 0.187 h and the apparent volume of distribution at steady state was 0.25 +/- 0.043 l/Kg. The total clearance (Cltot) was 0.435 +/- 0.031 l/h/kg, in which the renal clearance was 0.260 +/- 0.020 (about 60% of Cltot). The change in rate of urinary excretion of furosemide was similar to the plasma concentration decay curve. The diuretic effect of furosemide was accompanied by an extreme increase in the excretion rate of sodium and chloride, but not potassium. The relationships between the diuretic response and the plasma concentration or the urinary excretion rate of furosemide was depicted by sigmoidal dose-response curves in both cases. The half-maximum effect was obtained at 1.5 micrograms/ml of plasma concentration or at 80 micrograms/min of excretion rate of furosemide. PMID- 1433486 TI - Synovial and serum levels of triamcinolone following intra-articular administration of triamcinolone acetonide in the horse. AB - Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra-articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were assayed. The results show that the synovial fluid level of triamcinolone was 7.5 micrograms/ml 1 day following treatment and decreased to 10 ng/ml by the 4th day. These low levels were maintained for approximately 14 days. By the 15th day, the triamcinolone was below a detectable level. Serum levels of triamcinolone increased to 3 ng/ml within 1 h and further increased to a peak of 4.3 ng/ml at 4th h. The level then decreased to 2 ng/ml at 24 h and to nearly an undetectable level in 48 h. The mean level of serum cortisol, on the other hand, gradually decreased as the serum level of triamcinolone increased. As the serum level of triamcinolone reached an undetectable level on the 2nd day, the serum cortisol level gradually increased and returned to the pre-administration level by the 5th day. These results showed that the intra-articular administration of triamcinolone maintained triamcinolone in the synovial fluid for 4-14 days and that the triamcinolone reached the blood within 1 h. The serum level of triamcinolone was maintained for 2 days and resulted in the inhibition of adrenal function for 4 days. PMID- 1433487 TI - Effects of phenothiazine and thiabendazole on bovine dorsal pedal vein contractility induced by ergonovine and serotonin; potential for alleviation of fescue toxicity. AB - Phenothiazine and thiabendazole were studied for their ability to antagonize venoconstriction induced by ergonovine, and the biogenic amine serotonin, in the isolated dorsal pedal vein of cattle. The two compounds are commercially available, approved for usage in cattle and have been reported to reverse some of the toxic effects associated with the intake of Acremonium coenophialum-infested fescue forage by cattle. Neither compound had any antagonistic activity against venoconstriction induced by ergonovine. However, thiabendazole did have some activity against venoconstriction induced by serotonin. Ergot alkaloids are known to cause venoconstriction through effects on biogenic amine receptors, including serotonergic receptors, and since thiabendazole has anti-serotonin activity, part of the reported beneficial effects of thiabendazole in alleviating fescue toxicity may be due to the anti-serotonin activity of the drug. Further work is needed to determine if phenothiazine and thiabendazole have any effect on other types of alkaloids that are present in A. coenophialum-infested fescue. PMID- 1433488 TI - Acyclovir (Zovirax) pharmacokinetics in Quaker parakeets, Myiopsitta monachus. AB - The pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) single-dose administration of acyclovir were determined in Quaker parakeets. After i.v. injection at a dose of 20 mg/kg of acyclovir, elimination half-life was estimated at 0.65 h, volume of distribution at steady state was 627.65 ml/kg, and clearance was 11.22 ml/kg/min. The estimated pharmacokinetic values after i.m. injection at a dose of 40 mg/kg of acyclovir were an elimination half-life of 0.71 h and a bioavailability of 90.1%. The peak plasma acyclovir concentration occurred at 15 min when the drug was administered i.m. Plasma concentrations of acyclovir were undetectable 4-6 h after i.v. administration and 6-8 h after i.m. administration. Oral (capsules) and intravenous (sodium salt) formulations of acyclovir were given by gavage at 80 mg/kg. Peak concentrations with the sodium salt formulation were lower and developed more slowly than with the capsules. In studies designed to detect excessive drug accumulation or adverse side effects, acyclovir was administered i.m. at 40 mg/kg every 8 h for 7 days. Plasma concentrations were determined 15 min after (peak) and just prior to drug administration (trough). In another study acyclovir was gavaged at a dose of 80 mg/kg every 8 h for 4 days. Acyclovir plasma concentrations were determined just prior to and 2 h after drug administration. In both experiments, the birds maintained normal appetite and weight and did not exhibit excessive drug accumulation. Acyclovir plasma concentrations ranging from 2.07 +/- 1.09 micrograms/ml to 3.93 +/- 1.13 micrograms/ml were maintained for 4 days when acyclovir was administered in the feed and water (sole source of food and water).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433489 TI - Quantitative electroencephalography for measurement of central nervous system responses to diazepam and the benzodiazepine antagonist, flumazenil, in isoflurane-anaesthetized dogs. AB - Quantitative EEG was assessed in six dogs anaesthetized with 1.8% end-tidal isoflurane concentration and following diazepam (0.2 mg/kg i.v.) administration. Ventilation was controlled to maintain normocapnia. Five dogs were subsequently given the benzodiazepine antagonist, flumazenil (0.04 mg/kg i.v.), and quantitative EEG was recorded. One dog received a saline injection following diazepam (as a control) and quantitative EEG was recorded for an additional 2.5 h. Heart rate, arterial blood pressure, esophageal temperature, arterial pH and blood gas tensions, end-tidal CO2 tension and end-tidal isoflurane concentration were monitored throughout the study. A 21 lead linked-ear montage was used for recording EEG. Quantitative EEG data were stored on an optical disc for analysis at a later date. Values for absolute power of EEG were determined for theta, delta, alpha, and beta frequencies. Cardiovascular parameters remained stable throughout the study. Diazepam administration was associated with decreased absolute power in all frequencies of EEG at all electrode sites. The duration of diazepam-induced decreased absolute power of EEG was at least 3 h in one dog. Administration of flumazenil antagonized diazepam-induced decreased absolute power of EEG in all frequencies at all electrode sites. We conclude that quantitative EEG provides a relatively non-invasive, objective measure of diazepam- and flumazenil-induced changes in cortical activity during isoflurane anaesthesia. PMID- 1433490 TI - Methimazole-mediated modulation of netobimin biotransformation in sheep: a pharmacokinetic assessment. AB - The effects of modulation of liver microsomal sulphoxidation on the disposition kinetics of netobimin (NTB) metabolites were investigated in sheep. A zwitterion suspension of NTB was given orally at 7.5 mg/kg to sheep either alone (control treatment) or co-administered with methimazole (MTZ) orally (NTB + MTZ oral treatment) or intra-muscularly (NTB + MTZ i.m.) at 3 mg/kg. Blood samples were taken serially over a 72 h period and plasma was analysed by HPLC for NTB and its major metabolites, i.e. albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). Only trace amounts of NTB parent drug and ABZ were detected in the earliest samples after either treatment. There were significant modifications to the disposition kinetics of ABZSO in the presence of MTZ. ABZSO elimination half-life increased from 7.27 h (control treatment) to 14.57 h (NTB + MTZ oral) and to 11.39 h (NTB + MTZ i.m.). ABZSO AUCs were significantly higher (P less than 0.05) for the NTB + MTZ oral treatment (+55%) and for the NTB + MTZ i.m. treatment (+61%), compared with the NTB alone treatment. The mean residence times for ABZSO were 12.66 +/- 0.68 h (control treatment), 18.85 +/- 2.35 h (NTB + MTZ oral) and 17.02 +/- 0.90 h (NTB + MTZ i.m.). There were no major changes in the overall pharmacokinetics of ABZSO2 for the concomitant MTZ treatments. However, delayed appearance of this metabolite in the plasma resulted in longer ABZSO2 lag times and a delayed Tmax for treatments with MTZ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433491 TI - Comparative pharmacokinetics of the photosensitizer tin-etiopurpurin in dogs and rats. AB - Photodynamic therapy is a promising new treatment for local eradication of cancer. Little work has been done to define the pharmacokinetics of photodynamic drugs or the variability in drug disposition that may occur between different species and pathophysiological states of tissues. Pharmacokinetic studies of tin etiopurpurin (SnET2), a lipophilic photosensitizer, were conducted on six Beagle dogs and six Sprague-Dawley rats. Blood was collected up to 24 h following drug administration for measurement of tin-etiopurpurin concentration. Dogs and rats were euthanatized 24 h post-administration and tissues were collected for drug analyses. The plasma drug concentrations were best described by a 2-compartment model (Ct = Ae-alpha t + Be-beta t). Median distribution and elimination half lives were 0.24 and 0.34 h and 10.21 and 5.25 h for dogs and rats, respectively. The apparent volumes of distribution were 4.26 +/- 1.75 L/kg for dogs and 1.84 +/ 0.36 L/kg for rats. Systemic clearance was 7.56 +/- 2.45 ml/kg/min and 6.63 +/- 0.91 ml/kg/min for dogs and rats, respectively. Drug was detected in all tissues analyzed 24 h after drug administration. Drug was detected only sporadically in skin and muscle and was generally below the limit of detection of the assay. Where comparisons could be made, concentrations of SnET2 were significantly greater in all tissues except jejunum of rats compared to dogs 24 h after drug administration. PMID- 1433492 TI - Clorsulon pharmacokinetics in sheep and goats following oral and intravenous administration. AB - Clorsulon was measured in plasma and urine of sheep and goats after administration of a single intravenous (i.v.) and after a single oral dose of 7 mg/kg. A three-compartment model with elimination occurring from the central compartment was determined to best describe the i.v. data, whereas a one compartment model with a single exponential absorption phase best described the oral plasma data. The bioavailability of orally administered clorsulon was approximately 55% in goats and 60% in sheep. Peak plasma concentrations occurred at 14 h and 15 h after oral administration in goats and sheep, respectively. Absorption from the gastro-intestinal tract effectively prolonged the elimination of clorsulon by increasing the elimination half-life from 17 to 28 h in sheep and from 12 to 23 h in goats for the i.v. and oral routes, respectively. In both goats and sheep, approximately 50% of the i.v. dose was recovered in urine as parent drug at 48 h after administration, whereas 41% and 30% of the dose was recovered after oral administration for goats and sheep, respectively. The elimination rate constant (kel) in goats was nearly twice as large as the value determined in sheep, and the urea under the i.v. plasma curve in goats was only 63% of the value in sheep indicating that goats are more effective in their capacity to eliminate clorsulon than are sheep. These differences in drug disposition between sheep and goats may account for the reduced efficacy of clorsulon reported in goats. PMID- 1433493 TI - Plasma concentrations of flunixin in the horse: its relationship to thromboxane B2 production. AB - The effects of the intravenous (i.v.) administration of 1.1 mg/kg of flunixin meglumine on thromboxane B2 (TxB2) concentrations were studied in sedentary and 2 year-old horses in training. The baseline TxB2 serum concentrations generated during clotting were 2.89 +/- 0.81, 2.19 +/- 0.25 and 0.88 +/- 0.12 ng/ml for the 2-year-old Thoroughbreds in training, sedentary horses under 10 and over 10 years old, respectively. There was a significant difference in baseline TxB2 concentrations between older and younger horses (P less than 0.005). Significant reduction in TxB2 production from baseline were noted at 1 (P less than 0.01) and 4 h (P less than 0.01) but not at 8 h after flunixin administration. The percent reduction in serum TxB2 concentration at 1 h after the administration of flunixin was 68.6 +/- 7.3 and 45.2 +/- 6.8 for the training and sedentary horses, respectively; the differences were significant (P less than 0.04). Serum concentrations of TxB2 returned to baseline values by 12-16 h after flunixin administration. The results of this study indicate a difference in the TxB2 concentrations of older vs. younger horses and a difference in the suppression of TxB2 after the administration of flunixin in 2-year-old Thoroughbreds in training compared to sedentary horses. The results of this study suggest that the detection of low concentrations of flunixin in urine 24 h post-administration may not represent pharmacologic effective concentrations of flunixin in plasma. PMID- 1433494 TI - Pharmacokinetics of phenobarbital after repeated oral administration in normal horses. PMID- 1433495 TI - Rifampin disposition in the horse: effects of repeated dosage of rifampin or phenylbutazone. PMID- 1433496 TI - Pharmacokinetics of gentamicin and antipyrine in the horse--effect of advancing age. PMID- 1433497 TI - Identification and cloning of a novel heterogeneous nuclear ribonucleoprotein C like protein that functions as a transcriptional activator of the hepatitis B virus enhancer II. AB - Liver specificity of hepatitis B virus (HBV) replication has been attributed to the action of its second enhancer (EII). We report here the characterization of EII and the subsequent isolation of a novel liver-specific DNA-binding protein which binds to and activates EII. The cDNA clone of the protein, designated E2BP, was isolated from a lambda gt11 expression library constructed from the hepatoma cell line HuH-6 which was screened with a binding site probe derived from EII. Sequence analysis of E2BP revealed 86.6% homology with a rat heterogeneous nuclear ribonucleoprotein C protein sequence, while conformational studies suggest a helix-loop-helix motif as a DNA-binding site. Cloned E2BP expressed in human fibroblasts by transient transfection displayed EII binding and activating characteristics similar to those of native E2BP in hepatocytes. PMID- 1433498 TI - Translational stimulation by reovirus polypeptide sigma 3: substitution for VAI RNA and inhibition of phosphorylation of the alpha subunit of eukaryotic initiation factor 2. AB - COS cells transfected with plasmids that activate DAI depend on expression of virus-associated I (VAI) RNA to prevent the inhibitory effects of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha) kinase (DAI) and restore the translation of vector-derived dihydrofolate reductase mRNA. This VAI RNA requirement could be completely replaced by reovirus polypeptide sigma 3, consistent with its double-stranded RNA (dsRNA)-binding activity. S4 gene transfection of 293 cells also partially restored adenovirus protein synthesis after infection with the VAI-negative dl331 mutant. In dl331-infected 293 cells, eIF-2 alpha was present mainly in the acidic, phosphorylated form, and trans complementation with polypeptide sigma 3 or VAI RNA decreased the proportion of eIF-2 alpha (P) from approximately 85 to approximately 30%. Activation of DAI by addition of dsRNA to extracts of S4 DNA-transfected COS cells required 10-fold higher levels of dsRNA than extracts made from cells that were not producing polypeptide sigma 3. In extracts of reovirus-infected mouse L cells, the concentration of dsRNA needed to activate DAI was dependent on the viral serotype used for the infection. Although the proportion of eIF-2 alpha (P) was greater than that in uninfected cells, most of the factor remained in the unphosphorylated form, even at 16 h after infection, consistent with the partial inhibition of host protein synthesis observed with all three viral serotypes. The results indicate that reovirus polypeptide sigma 3 participates in the regulation of protein synthesis by modulating DAI and eIF-2 alpha phosphorylation. PMID- 1433499 TI - Enhancement of polyhedrin nuclear localization during baculovirus infection. AB - Polyhedrin is the major component of the nuclear viral occlusions produced during replication of the baculovirus Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV). Since viral occlusions are responsible for the horizontal transmission of AcMNPV in nature, the biosynthesis, localization, and assembly of polyhedrin are important events in the viral replication cycle. We recently defined the sequence requirements for nuclear localization and assembly of polyhedrin. In this study, we examined the localization of polyhedrin at different times of infection. The results showed that nuclear localization of polyhedrin becomes more efficient as the occlusion phase of infection progresses. Several different factors were identified that might contribute to this overall effect, including a higher rate of polyhedrin nuclear localization and a higher rate of polyhedrin biosynthesis. We also examined the biosynthesis and processing of polyhedrin in cells infected with an AcMNPV few polyhedra (FP) mutant, which produces smaller numbers of viral occlusions that contain few or no virions. Compared with wild type, the FP mutant produced polyhedrin more slowly and localized it to the nucleus less efficiently at the beginning of the occlusion phase of infection (24 h postinfection). This supported the idea that the efficiency of polyhedrin nuclear localization is tightly coupled to its rate of biosynthesis. It also revealed that expression of the viral 25K gene, which is inactivated in the FP mutant, is directly or indirectly associated with an enhancement of polyhedrin biosynthesis and nuclear localization at the beginning of the occlusion phase of infection. This enhancement effect appears to be necessary to ensure the normal assembly of viral occlusions. PMID- 1433500 TI - Sulfation of the human immunodeficiency virus envelope glycoprotein. AB - Sulfation is a posttranslational modification of proteins which occurs on either the tyrosine residues or the carbohydrate moieties of some glycoproteins. In the case of secretory proteins, sulfation has been hypothesized to act as a signal for export from the cell. We have shown that the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein precursor (gp160) as well as the surface (gp120) and transmembrane (gp41) subunits can be specifically labelled with 35SO42-. Sulfated HIV-1 envelope glycoproteins were identified in H9 cells infected with the IIIB isolate of HIV-1 and in the cell lysates and culture media of cells infected with vaccinia virus recombinants expressing a full-length or truncated, secreted form of the HIV-1 gp160 gene. N-glycosidase F digestion of 35SO4(2-)-labelled envelope proteins removed virtually all radiolabel from gp160, gp120, and gp41, indicating that sulfate was linked to the carbohydrate chains of the glycoprotein. The 35SO42-label was at least partially resistant to endoglycosidase H digestion, indicating that some sulfate was linked to complex carbohydrates. Brefeldin A, a compound that inhibits the endoplasmic reticulum to Golgi transport of glycoproteins, was found to inhibit the sulfation of the envelope glycoproteins. Envelope glycoproteins synthesized in cells treated with chlorate failed to incorporate 35SO42-. However, HIV glycoproteins were still secreted from cells in the presence of chlorate, indicating that sulfation is not a requirement for secretion of envelope glycoproteins. Sulfation of HIV-2 and simian immunodeficiency virus envelope glycoproteins has also been demonstrated by using vaccinia virus-based expression systems. Sulfation is a major determinant of negative charge and could play a role in biological functions and antigenic properties of HIV glycoproteins. PMID- 1433501 TI - Plasmid models for bacteriophage T4 DNA replication: requirements for fork proteins. AB - Bacteriophage T4 DNA replication initiates from origins at early times of infection and from recombinational intermediates as the infection progresses. Plasmids containing cloned T4 origins replicate during T4 infection, providing a model system for studying origin-dependent replication. In addition, recombination-dependent replication can be analyzed by using cloned nonorigin fragments of T4 DNA, which direct plasmid replication that requires phage-encoded recombination proteins. We have tested in vivo requirements for both plasmid replication model systems by infecting plasmid-containing cells with mutant phage. Replication of origin and nonorigin plasmids strictly required components of the T4 DNA polymerase holoenzyme complex. Recombination-dependent plasmid replication also strictly required the T4 single-stranded DNA-binding protein (gene product 32 [gp32]), and replication of origin-containing plasmids was greatly reduced by 32 amber mutations. gp32 is therefore important in both modes of replication. An amber mutation in gene 41, which encodes the replicative helicase of T4, reduced but did not eliminate both recombination- and origin dependent plasmid replication. Therefore, gp41 may normally be utilized for replication of both plasmids but is apparently not required for either. An amber mutation in gene 61, which encodes the T4 RNA primase, did not eliminate either recombination- or origin-dependent plasmid replication. However, plasmid replication was severely delayed by the 61 amber mutation, suggesting that the protein may normally play an important, though nonessential, role in replication. We deleted gene 61 from the T4 genome to test whether the observed replication was due to residual gp61 in the amber mutant infection. The replication phenotype of the deletion mutant was identical to that of the amber mutant. Therefore, gp61 is not required for in vivo T4 replication. Furthermore, the deletion mutant is viable, demonstrating that the gp61 primase is not an essential T4 protein. PMID- 1433502 TI - Down-regulation of the major histocompatibility complex class I enhancer in adenovirus type 12-transformed cells is accompanied by an increase in factor binding. AB - In transformed cells, the E1A gene of adenovirus type 12 (Ad12) represses transcription of class I genes of the major histocompatibility complex. The tumorigenic potential of Ad12-transformed cells correlates with this diminished class I expression. In contrast, the E1A gene of the nontumorigenic Ad5 does not affect class I expression. We show here that a transfected reporter chloramphenicol acetyltransferase plasmid driven by an H-2K promoter (-1049 bp) was expressed at much lower levels in Ad12- than in Ad5-transformed mouse cells. Analysis of mutant constructs revealed that only 83 bp of H-2 DNA, consisting of the enhancer juxtaposed to the basal promoter, was sufficient for this differential expression. Whereas the H-2 basal promoter alone was somewhat less active in Ad12-transformed cells, the H-2 TATA box itself did not appear to be important. The H-2 enhancer proved to be the principal element in Ad12 E1A mediated repression, since (i) substitution of the H-2 enhancer by simian virus 40 enhancers overcame the repression, and (ii) when juxtaposed to either its native or heterologous basal promoters, the H-2 enhancer was functional in Ad5- but not Ad12-transformed cells. Mobility shift assays showed that there is a DNA binding activity to the 5' site (R2 element) of the enhancer that is significantly higher in Ad12- than in Ad5-transformed cells. These results suggest that decreased class I enhancer activity in Ad12-transformed cells may, at least in part, be due to the higher levels of an enhancer-specific factor, possibly acting as a repressor. PMID- 1433504 TI - Localization of an immunodominant domain on baculovirus-produced parvovirus B19 capsids: correlation to a major surface region on the native virus particle. AB - An immunodominant region on baculovirus-produced parvovirus B19 VP2 capsids was localized between amino acids 259 and 426 by mapping the binding sites of a panel of monoclonal antibodies which recognize determinants on the particles. The binding sites of three monoclonal antibodies were fine-mapped within this antigenic domain. Six VP2-specific monoclonal antibodies recognized determinants common to both the empty capsids and native parvovirus. The defined antigenic region is most probably exposed on the native B19 virion and corresponds to part of the threefold spike on the surface of canine parvovirus particles. PMID- 1433503 TI - Negative regulation of the major histocompatibility complex class I enhancer in adenovirus type 12-transformed cells via a retinoic acid response element. AB - In cells transformed by the highly oncogenic adenovirus type 12 (Ad12), the viral E1A proteins mediate transcriptional repression of the major histocompatibility class I genes. In contrast, class I transcription is not reduced in cells transformed by the nononcogenic Ad5. The decreased rate of class I transcription is, at least in part, the result of a reduced major histocompatibility complex class I enhancer activity in Ad12-transformed cells and correlates with an increase in the levels of a DNA-binding activity to the R2 element of the enhancer (R. Ge, A. Kralli, R. Weinmann, and R. P. Ricciardi, J. Virol. 66:6969 6978, 1992). Employing transient transfection assays, we now provide direct evidence that the R2 element can confer repression in Ad12- but not Ad5 transformed cells. Repression by R2 was observed only in the presence of the positive enhancer element R1 and was dependent on (i) the number of the R2 elements and (ii) the relative arrangement of R2 and R1 elements. The putative R2 binding repressor protein, R2BF, was similar in molecular weight and binding specificity to members of the thyroid hormone/retinoic acid (RA) receptor family. RA treatment abrogated the R2-mediated repression in Ad12-transformed cells and had no effect on the activity of R2/R1-containing promoters in Ad5-transformed cells. These results are consistent with the presence of an R2-binding repressor in Ad12-transformed cells. In the absence of RA, the repressor compromises enhancer activity by interfering with the activity of the positive cis element R1. RA treatment of Ad12-transformed cells may render the repressor inactive. PMID- 1433505 TI - Importance of p12 protein in Mason-Pfizer monkey virus assembly and infectivity. AB - Mason-Pfizer monkey virus (M-PMV) represents the prototype type D retrovirus, characterized by the assembly of intracytoplasmic A-type particles within the infected-cell cytoplasm. These immature particles migrate to the plasma membrane, where they are released by budding. The gag gene of M-PMV encodes a novel protein, p12, just 5' of the major capsid protein (CA) p27 on the polyprotein precursor. The function of p12 is not known, but an equivalent protein is found in mouse mammary tumor virus and is absent from the type C retroviruses. In order to determine whether the p12 protein plays a role in the intracytoplasmic assembly of capsids, a series of in-frame deletion mutations were constructed in the p12 coding domain. The mutant gag genes were expressed by a recombinant vaccinia virus-T7 polymerase-based system in CV-1 cells or in the context of the viral genome in COS-1 cells. In both of these high-level expression systems, mutant Gag precursors were competent to assemble but were not infectious. In contrast, when stable transfectant HeLa cell lines were established, assembly of the mutant precursors into capsids was drastically reduced. Instead, the polyprotein precursors remained predominantly soluble in the cytoplasm. These results show that while p12 is not required for the intracytoplasmic assembly of M-PMV capsids, under the conditions of low-level protein biosynthesis seen in virus-infected cells, it may assist in the stable association of polyprotein precursors for capsid assembly. Moreover, the presence of the p12 coding domain is absolutely required for the infectivity of M-PMV virions. PMID- 1433506 TI - Role of ribosomes in Semliki Forest virus nucleocapsid uncoating. AB - The mechanism by which Semliki Forest virus nucleocapsids are uncoated was analyzed in living cells and in vitro. In BHK-21 cells, uncoating occurred with virtually complete efficiency within 1 to 2 min after the nucleocapsids entered the cytoplasm. It was inhibited by monensin, which blocks nucleocapsid penetration from endosomes. As previously shown for Sindbis virus (G. Wengler and G. Wengler, Virology 134:435-442, 1984), the capsid proteins from incoming nucleocapsids became associated with ribosomes. The ribosome-bound capsid proteins were distributed throughout the cytoplasm, while the viral RNA remained associated with vacuolar membranes. Using purified nucleocapsids and ribosomes in vitro, we established that ribosomes alone were sufficient for uncoating. Their role was to release the capsid proteins from nucleocapsids and irreversibly sequester them, in a process independent of energy and translation. The process was stoichiometric rather than catalytic, with a maximum of three to six capsid proteins bound to each ribosome. More than 80% of the capsid proteins could thus be removed from the viral RNA, resulting in the formation of nucleocapsid remnants whose sedimentation coefficients progressively decreased from 140S to 80S as uncoating proceeded. PMID- 1433507 TI - Serial backcross analysis of genetic resistance to mousepox, using marker loci for Rmp-2 and Rmp-3. AB - At least three genes from C57BL/6 mice that mediate dominant resistance to lethal mousepox were isolated and transferred onto a susceptible DBA/2 background. Three [(C57BL/6 x DBA/2)F1 x DBA/2] male mice that survived infection were selected as founders on the basis of different complements of marker loci for two resistance genes, Rmp-2r (Hc1) and Rmp-3r (H-2Db). They were crossed with DBA/2 mice, male progeny were infected with ectromelia virus, and the cycle was repeated with surviving male progeny through seven backcross generations. Two founders carried a marker locus for Rmp-2r or Rmp-3r, and the third carried neither marker locus. Resistance pedigrees were analyzed for passage of marker loci. From the three founders, resistance was passaged through multiple generations, producing backcross lines with intermediate-male-resistance phenotypes (20% resistant). Females of backcross lines with intermediate male resistance had high resistance (> 50%). High-resistance backcross lines (40% male resistance) also developed from the founders that carried marker loci for Rmp-2r and Rmp-3r, and marker loci were passaged through all generations of high resistance but not intermediate resistance lines. About one-third of all resistant mice in high-resistance lines sired by mice that carried marker loci for Rmp-2r and Rmp-3r did not carry the respective marker locus. In lines that carried Rmp-2r, this was apparently not the result of recombination between Rmp-2r and Hc1, because Rmp-2 was not in the predicted location on chromosome 2 and because mice that did not inherit Hc1 transmitted significantly less male resistance than Hc1-positive mice, although female resistance remained high. These results confirmed that C57BL/6 mice have redundant resistance mechanisms, two of which are controlled at least in part by Rmp-2r and Rmp-3r, and provided evidence for a fourth resistance gene, herein presumptively named Rmp-4, which protects females more than males and which may be epistatic to Rmp-2. PMID- 1433508 TI - Baculovirus phosphoprotein pp31 is associated with virogenic stroma. AB - The PstI K fragment of Autographa californica nuclear polyhedrosis virus (AcMNPV) encodes a protein with a molecular weight of 31,000. To define the role of this protein (pp31) in virus infection further, it was overexpressed in bacteria and used to produce polyclonal antiserum. Radioimmunoprecipitation analysis indicated that pp31 was synthesized during both the early and late phases of virus infection, consistent with previous analyses indicating that the gene was regulated by tandem early and late promoters. Metabolic labeling of cells with carrier-free phosphate indicated that pp31 was phosphorylated. Biochemical fractionation experiments showed that pp31 was localized in the nucleus and that it was more stably associated with the nucleus at later times of infection. Immunoblot analysis of subnuclear fractions indicated that pp31 was associated predominantly with the chromatin and nuclear matrix fractions. Immunofluorescence experiments confirmed that the pp31 protein was localized in the nucleus. Nuclear staining was relatively uniform early but was more centrally nuclear later in infection. Immunoelectron microscopy indicated that the pp31 protein was a component of virogenic stroma. Southwestern (DNA-protein) blot analysis demonstrated that pp31 is a DNA-binding protein. These findings suggest a possible role for pp31 in the virus life cycle. PMID- 1433509 TI - Attenuation of Sindbis virus neurovirulence by using defined mutations in nontranslated regions of the genome RNA. AB - We examined a panel of Sindbis virus mutants containing defined mutations in the 5' nontranslated region of the genome RNA, in the 3' nontranslated region, or in both for their growth in cultured cells and virulence in newborn mice. In cultured cells, these viruses all had defects in RNA synthesis and displayed a wide range of growth rates. The growth properties of the mutants were often very different in mouse cells from those in chicken cells or in mosquito cells. We hypothesize that host factors, presumably proteins, interact with these nontranslated regions to promote viral replication and that the mammalian protein and the chicken or mosquito protein are sufficiently divergent that alterations in the viral RNA sequence can affect the interactions with these different host proteins in different ways. Some of the mutants were temperature sensitive for plaque formation, whereas one mutant was slightly cold sensitive in its growth in chicken cells. Upon inoculation into mice, viruses that grew well in cultured mouse cells retained their virulence, but mice that succumbed usually had extended survival times. One virulent mutant that grew slightly less well in cultured mouse cells than did the parental virus produced eight times as much virus in mouse brain following intracerebral inoculation, suggesting that changes in these regulatory regions may have tissue-specific as well as host-specific effects. Viruses that were severely crippled in their growth in mouse cells in culture were usually, but not always, attenuated in their virulence. In particular, temperature sensitivity was correlated with attenuation. The effect of two mutations was found to be cumulative, and double mutants that contained mutations in both the 5' and 3' nontranslated regions were more attenuated than was either single mutant. Three of four double mutants tested were severely crippled for virus production in cultured cells and were avirulent for mice, even when inoculated intracerebrally. PMID- 1433510 TI - Mutational inactivation of an inhibitory sequence in human immunodeficiency virus type 1 results in Rev-independent gag expression. AB - We have characterized an inhibitory RNA element in the human immunodeficiency virus type 1 (HIV-1) gag coding sequence that prevents gag expression. The inhibition exerted by this element could be overcome by the presence of the Rev responsive element in cis and of Rev protein in trans. To understand the mechanism of function, we inactivated the inhibitory element by mutagenesis while maintaining an intact gag coding region. A constitutive high level of Rev independent gag expression was achieved only after the introduction of 28 point mutations over a large region of 270 nucleotides within the gag coding region. To our knowledge, this is the first demonstration of inactivation of a negative RNA element within a coding region without alteration of the expressed protein. Elimination of the inhibitory element in the p17gag region, named INS-1, offered the opportunity to detect a second inhibitory element in the gag-pol region. The presence of either INS element is sufficient to inhibit gag expression, demonstrating that multiple INS elements acting independently can inhibit HIV RNA expression. Expression of gag from Rous sarcoma virus, a retrovirus that does not require Rev-like regulatory proteins, revealed that the Rous sarcoma virus p19gag region does not contain inhibitory elements. These results demonstrate the presence of a strong inhibitory element acting at the level of mRNA and provide a general method for the removal of such elements from mRNA coding regions. The inhibitory element functions in the absence of any HIV-1 proteins, suggesting that cellular factors are responsible for this inhibition. PMID- 1433511 TI - Mutational analysis of human T-cell leukemia virus type I Tax: regions necessary for function determined with 47 mutant proteins. AB - We have made 47 mutations that span the length of the human T-cell leukemia virus type I (HTLV-I) Tax open reading frame. Of the 47 mutations, 38 were substitutions of single amino acids, 5 were missense changes in two or more amino acids, and 4 were deletions. A subset of these mutations includes individual changes of all 26 naturally occurring serines to alanines. By assaying each mutant protein separately on the HTLV-I long terminal repeat (LTR) and the human immunodeficiency virus type 1 (HIV-1) LTR in parallel, we were able to identify regions of Tax selectively necessary for each promoter. A small region in the carboxyl terminus, amino acids 315 to 325, was found to be selectively important for activation of the HTLV-I LTR. Three changes at serine 113, serine 160, and serine 258 were found to specifically affect function on the HIV-1 LTR. Surprisingly, we found that the great preponderance of missense changes (32 of 42) in Tax did not affect function. PMID- 1433512 TI - Human immunodeficiency virus type 1 Vpu protein induces rapid degradation of CD4. AB - CD4 is an integral membrane glycoprotein which is known as the human immunodeficiency virus (HIV) receptor for infection of human cells. The protein is synthesized in the endoplasmic reticulum (ER) and subsequently transported to the cell surface via the Golgi complex. HIV infection of CD4+ cells leads to downmodulation of cell surface CD4, due at least in part to the formation of stable intracellular complexes between CD4 and the HIV type 1 (HIV-1) Env precursor polyprotein gp160. This process "traps" both proteins in the ER, leading to reduced surface expression of CD4 and reduced processing of gp160 to gp120 and gp41. We have recently demonstrated that the presence of the HIV-1 encoded integral membrane protein Vpu can reduce the formation of Env-CD4 complexes, resulting in increased gp160 processing and decreased CD4 stability. We have studied the effect of Vpu on CD4 stability and found that Vpu induces rapid degradation of CD4, reducing the half-life of CD4 from 6 h to 12 min. By using a CD4-binding mutant of gp160, we were able to show that this Vpu-induced degradation of CD4 requires retention of CD4 in the ER, which is normally accomplished through its binding to gp160. The involvement of gp160 in the induction of CD4 degradation is restricted to its function as a CD4 trap, since, in the absence of Env, an ER retention mutant of CD4, as well as wild-type CD4 in cultures treated with brefeldin A, a drug that blocks transport of proteins from the ER, is degraded in the presence of Vpu. PMID- 1433513 TI - U3 long terminal repeat-mediated induction of intracellular immunity by a murine retrovirus: a novel model of latency for retroviruses. AB - BL/VL3 radiation leukemia virus (RadLV) is a thymotropic, highly leukemogenic murine leukemia virus (MuLV) which is unable to replicate in vitro in mouse fibroblasts. We have previously reported that the U3 long terminal repeat region of its genome is responsible for this block (E. Rassart, Y. Paquette, and P. Jolicoeur, J. Virol. 62:3840-3848, 1988). By using hybrids of permissive and resistant cells infected with BL/VL3 RadLV or fibrotropic MuLV, we found that the resistant phenotype was dominant. Investigation to determine at which step of the virus cycle the block operates revealed that integration, transcription, and translation of the BL/VL3 viral genome occurred at normal levels in nonpermissive cells. The BL/VL3 RadLV Pr65gag proteins made in nonpermissive cells were also myristylated and located at the membrane, and the levels of their cleaved products were similar to those of fibrotropic MuLV. However, processing of BL/VL3 RadLV Pr85env was impaired in nonpermissive cells. Virions were not released into the culture medium of nonpermissive cells, as measured by reverse transcriptase activity and by content in p30 or gp70 protein and as documented by lower levels of budding particles seen by electron microscopy. These results indicate that BL/VL3 RadLV replication is blocked at a late stage of the virus cycle, i.e., at virion assembly. Interestingly, these BL/VL3 RadLV-infected nonpermissive fibroblasts were resistant to superinfection by fibrotropic Moloney MuLV, and this resistance also occurred at a late step of the Moloney virus cycle. Since this block is dominant, it appears that the U3 long terminal repeat region of the BL/VL3 viral genome has the ability to induce a cellular suppressor factor(s), thus bringing intracellular immunity against itself and against other ecotropic MuLVs. PMID- 1433514 TI - Characterization of a vaccinia virus-encoded 42-kilodalton class I membrane glycoprotein component of the extracellular virus envelope. AB - Using a reverse genetic approach, we have demonstrated that the product of the B5R open reading frame (ORF), which has homology with members of the family of complement control proteins, is a membrane glycoprotein present in the extracellular enveloped (EEV) form of vaccinia virus but absent from the intracellular naked (INV) form. An antibody (C'-B5R) raised to a 15-amino-acid peptide from the translated B5R ORF reacted with a 42-kDa protein (gp42) found in vaccinia virus-infected cells and cesium chloride-banded EEV but not INV. Under nonreducing conditions, an 85-kDa component, possibly representing a hetero- or homodimeric form of gp42, was detected by both immunoprecipitation and Western immunoblot analysis. Metabolic labeling with [3H]glucosamine and [3H]palmitate revealed that the B5R product is glycosylated and acylated. The C-terminal transmembrane domain of the protein was identified by constructing a recombinant vaccinia virus that overexpressed a truncated, secreted form of the B5R ORF product. By N-terminal sequence analysis of this secreted protein, the site of signal peptide cleavage of gp42 was determined. A previously described monoclonal antibody (MAb 20) raised to EEV, which immunoprecipitated a protein with biochemical characteristics similar to those of wild-type gp42, reacted with the recombinant, secreted product of the B5R ORF. Immunofluorescence of wild-type vaccinia virus-infected cells by using either MAb 20 or C'-B5R revealed that the protein is expressed on the cell surface and within the cytoplasm. Immunogold labeling of EEV and INV with MAb 20 demonstrated that the protein was found exclusively on the EEV membrane. PMID- 1433515 TI - Mutational analysis of the octapeptide sequence motif at the NS1-NS2A cleavage junction of dengue type 4 virus. AB - We have previously shown that proper processing of dengue type 4 virus NS1 from the NS1-NS2A region of the viral polyprotein requires a hydrophobic N-terminal signal and the downstream NS2A. Results from deletion analysis indicate that a minimum length of eight amino acids at the C terminus of NS1 is required for cleavage at the NS1-NS2A junction. Comparison of this eight-amino-acid sequence with the corresponding sequences of other flaviviruses suggests a consensus cleavage sequence of Met/Leu-Val-Xaa-Ser-Xaa-Val-Xaa-Ala. Site-directed mutagenesis was performed to construct mutants of NS1-NS2A that contained a single amino acid substitution at different positions of the consensus cleavage sequence or at the immediate downstream position. Three to eight different substitutions were made at each position. A total of 50 NS1-NS2A mutants were analyzed for their cleavage efficiency relative to that of the wild-type dengue type 4 virus sequence. As predicted, nearly all substitutions at positions P1, P3, P5, P7, and P8, occupied by conserved amino acids, yielded low levels of cleavage, with the exception that Pro or Ala substituting for Ser (P5) was tolerated. Substitutions of an amino acid at the remaining positions occupied by nonconserved amino acids generally yielded high levels of cleavage. However, some substitutions at nonconserved positions were not tolerated. For example, substitution of Gly or Glu for Gln (P4) and substitution of Val or Glu for Lys (P6) each yielded a low level of cleavage. Overall, these data support the proposed cleavage sequence motif deduced by comparison of sequences among the flaviviruses. This study also showed that in addition to the eight-amino-acid sequence, the amino acid immediately following the NS1-NS2A cleavage site plays a role in cleavage. PMID- 1433516 TI - Posttranscriptional regulation by the human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex proteins through a heterologous RNA binding site. AB - The human immunodeficiency virus type 1 Rev and human T-cell leukemia virus type I Rex proteins induce cytoplasmic expression of incompletely spliced viral mRNAs by binding to these mRNAs in the nucleus. Each protein binds a specific cis acting element in its target RNAs. Both proteins also associated with nucleoli, but the significance of this association is uncertain because mutations that inactivate nucleolar localization signals in Rev or Rex also prevent RNA binding. Here we demonstrate that Rev and Rex can function when tethered to a heterologous RNA binding site by a bacteriophage protein. Under these conditions, cytoplasmic accumulation of unspliced RNA occurs without the viral response elements, mutations in the RNA binding domain of Rev do not inhibit function, and nucleolar localization can be shown to be unnecessary for the biological response. PMID- 1433517 TI - Expression and characterization of the trans-activating protein Tax of human T cell leukemia virus type I in Saccharomyces cerevisiae. AB - The trans-activator protein Tax of human T-cell leukemia virus type I (HTLV-I) stimulates transcription of the viral genome from the long terminal repeat. With a reporter HIS4TATA::lacZ fusion gene, the transcriptional activity of the Tax responsive element in the long terminal repeat was tested in Saccharomyces cerevisiae. We found that fragments containing the 21-bp repeat of the HTLV-I enhancer stimulate synthesis of beta-galactosidase activity 15- to 20-fold. To test the ability of the Tax protein to trans activate the HTLV-I enhancer in yeast cells, the pX region of HTLV-I, encoding the Tax protein, was cloned under the control of the yeast GAL1 promoter. The expressed Tax protein is localized in the nucleus and associated with the yeast nuclear matrix fraction. In yeast cells that contained the integrated tax gene, two- to sixfold stimulation of expression from the HTLV-I enhancer was detected at the early stages of tax induction. This in vivo reconstitution system provides a new approach for examining the host factor(s), the signal transduction mechanism(s), and the role of nuclear architecture involved in Tax-mediated trans activation. PMID- 1433518 TI - The requirements for viral entry differ from those for virally induced syncytium formation in NIH 3T3/DTras cells exposed to Moloney murine leukemia virus. AB - Moloney murine leukemia virus (Mo-MuLV) has the unique ability to infect different cells via either a low-pH-dependent or a pH-independent entry pathway. Only the pH-independent mechanism of Mo-MuLV entry has been associated with Mo MuLV-induced syncytium formation. We have now identified a transformed cell line (NIH 3T3/DTras) which efficiently forms syncytia when exposed to Mo-MuLV, yet is low pH dependent for Mo-MuLV entry. Treatment of NIH 3T3/DTras cells with chloroquine, an agent which raises endosomal pH, blocks Mo-MuLV entry, but not Mo MuLV-induced syncytium formation. This demonstrates that fusion which accompanies viral entry and fusion which is responsible for syncytium formation occur as independent processes in these cells. In addition, we determined that neither inherent differences in the Mo-MuLV receptor nor reduced affinity for Mo-MuLV gp70 can account for resistance of NIH 3T3 cells to Mo-MuLV-induced syncytium formation. PMID- 1433519 TI - Identification of the domains required for direct interaction of the helicase like and polymerase-like RNA replication proteins of brome mosaic virus. AB - Brome mosaic virus is a positive-strand RNA virus whose RNA replication requires viral protein 1a, which has putative helicase and capping functions, and 2a, which has putative polymerase function. Since domains of related sequence are conserved in a wide range of plus-strand RNA viruses, analysis of 1a and 2a function should have applicability to many other viruses. We have recently demonstrated that 1a and 2a form a complex in vivo and in vitro. Using immune coprecipitation and mutant polypeptides made in reticulocyte lysates, we have now mapped both the 1a and 2a domains necessary for complex formation. The sequences needed to bind 2a map to the carboxy-terminal helicase-like domain of 1a. Truncated polypeptides containing this domain were able to bind to 2a, while several small insertions in the helicase-like domain disrupted binding. The sequence required for binding 1a lies within a 115-residue subset of the 2a N terminal segment preceding the polymerase-like domain. Truncations or fusion polypeptides containing this segment can bind 1a. We also determined that highly purified 2a protein made in insect cells can form a complex with highly purified 1a helicase-like domain made in Escherichia coli, suggesting that no other factor is required to mediate 1a-2a interaction. Previous genetic analyses of 1a and 2a are consistent with this mapping and show that the newly defined 1a and 2a binding regions are required for RNA synthesis. The locations of these interacting regions are discussed with regard to models of viral replication and the evolution of positive-strand RNA virus genomes. PMID- 1433520 TI - Membrane fusion of Semliki Forest virus involves homotrimers of the fusion protein. AB - Infection of cells with enveloped viruses is accomplished through membrane fusion. The binding and fusion processes are mediated by the spike proteins in the envelope of the virus particle and usually involve a series of conformational changes in these proteins. We have studied the low-pH-mediated fusion process of the alphavirus Semliki Forest virus (SFV). The spike protein of SFV is composed of three copies of the protein heterodimer E2E1. This structure is resistant to solubilization in mild detergents such as Nonidet P-40 (NP40). We have recently shown that the spike structure is reorganized during virus entry into acidic endosomes (J. M. Wahlberg and H. Garoff, J. Cell Biol. 116:339-348, 1992). The original NP40-resistant heterodimer is dissociated, and the E1 subunits form new NP40-resistant protein oligomers. Here, we show that the new oligomer is represented by an E1 trimer. From studies that use an in vitro assay for fusion of SFV with liposomes, we show that the E1 trimer is efficiently expressed during virus-mediated membrane fusion. Time course studies show that both E1 trimer formation and fusion are fast processes, occurring in seconds. It was also possible to inhibit virus binding and fusion with a monoclonal antibody directed toward the trimeric E1. These results give support for a model in which the E1 trimeric structure is involved in the SFV-mediated fusion reaction. PMID- 1433521 TI - Molecular profile of human immunodeficiency virus type 1 infection in symptomless patients and in patients with AIDS. AB - Recent molecular evidence indicates that active human immunodeficiency virus type 1 (HIV-1) infection is detectable in both symptomless and symptomatic infected patients. For this main reason, it has been pointed out that precise quantitative analysis of viral activity in vivo is necessary, firstly, for the pathogenetic investigation of the steps relevant to infection progression and, secondly, for better clinical management of HIV-1-infected patients. In this study, the presence of HIV-1 genomic RNA in plasma samples, specific HIV-1 transcripts in peripheral blood mononuclear cells, and proviral DNA sequences were assayed for 33 HIV-1-infected patients (including symptomless and symptomatic subjects) by using a competitive polymerase chain reaction method that allows quantitation of the RNA/DNA target sequences. The quantitative results obtained confirm that transcription of HIV-1 structural genes and complete viral replication occur in all the HIV-1-infected patients independently of the clinical stage. However, although sharp individual differences were detected, a high degree of correlation of the molecular parameters studied with both disease progression and a decrease in the number of CD4+ T lymphocytes was documented. Interestingly, despite the increasing viremia level associated with infection progression, the mean transcriptional activity of individual infected cells was found to be only moderately greater in AIDS patients than in asymptomatic infected subjects. In addition, it was noted that quantitation of HIV-1 genomic RNA in plasma samples and quantitation of specific HIV-1 transcripts in peripheral blood mononuclear cells appear to be more reliable and sensitive markers of viral activity than quantitative analysis of proviral HIV-1 sequences in peripheral lymphocytes. PMID- 1433522 TI - Promoter influence on baculovirus-mediated gene expression in permissive and nonpermissive insect cell lines. AB - The activities of viral and insect promoters were examined in a range of insect cell lines permissive and nonpermissive for the replication of the baculovirus Autographa californica nuclear polyhedrosis virus. Recombinant baculoviruses were constructed to place the bacterial chloramphenicol acetyltransferase gene under the control of promoters strongly active in the early, late, or very late stages of virus replication. In fully permissive cells, expression from a very late promoter was 2- to 3-fold higher than expression from a late promoter and 10- to 20-fold higher than expression from an early promoter or from a virus-borne insect promoter. In cell lines that do not support the efficient production of viral progeny, late-promoter-driven expression was similar to or surpassed very late promoter-driven expression. In nonpermissive insect cell lines, expression driven by an insect promoter derived from Drosophila melanogaster was higher than expression from the three viral promoters and was especially high in the Drosophila cell line tested. Surprisingly, late-promoter-driven expression, which is dependent on DNA replication, was higher than early-promoter-driven expression in three of four nonpermissive lines. In contrast, very late promoter-driven expression was quite limited in nonpermissive cell lines. The results indicate that the promoter used to drive foreign-gene expression strongly influences the range of insect cells which can efficiently support the production of the foreign protein during infection with recombinant baculoviruses. PMID- 1433523 TI - Requirement of active human immunodeficiency virus type 1 integrase enzyme for productive infection of human T-lymphoid cells. AB - The human immunodeficiency virus type 1 (HIV-1) integrase enzyme exhibits significant amino acid sequence conservation with integrase proteins of other retroviruses. We introduced specific amino acid substitutions at a number of the conserved residue positions of recombinant HIV-1 integrase. Some of these substitutions resulted in proteins which were not able to be purified in the same manner as the wild-type enzyme, and these were not studied further. The remaining mutant enzymes were assessed for their abilities to perform functions characteristic of the integrase protein. These included specific removal of the terminal dinucleotides from oligonucleotide substrates representative of the viral U5-long terminal repeat, nonspecific cleavage of oligonucleotide substrates, and mediation of the strand transfer (integration) reaction. Substitution at position 43, within the protein's zinc finger motif region, resulted in an enzyme with reduced specificity for cleavage of the terminal dinucleotide. In addition, a double substitution of aspartic acid and glutamine for valine and glutamic acid, respectively, at positions 151 and 152 within the D,D(35)E motif region rendered the integrase protein inactive for all of its functions. The introduction of this double substitution into an infectious HIV-1 provirus yielded a mutant virus that was incapable of productively infecting human T-lymphoid cells in culture. PMID- 1433524 TI - Functional dissection of the Autographa californica nuclear polyhedrosis virus immediate-early 1 transcriptional regulatory protein. AB - Autographa californica multicapsid nuclear polyhedrosis virus-infected insect cells express a viral immediate-early transcriptional regulatory protein, IE1, that has been shown by transient-expression assays to stimulate the expression of certain baculovirus delayed-early (DE) promoters and to inhibit the expression of other immediate-early (IE) genes. It is believed that certain DE promoters are activated, in part, by direct interactions between IE1 and enhancer elements located in regions adjacent to these genes. We have used transient cotransfection and DNA-binding assays to examine the function of mutant forms of IE1. Our results indirectly show that IE1 has at least two separable domains that are essential for its role in the modulation of baculovirus gene expression. A domain rich in acidic residues and essential for transactivation is located within the N terminal 145 amino acids of the polypeptide. A second domain, located in the C terminal 437 amino acids of IE1, is required for inhibitory and DNA-binding activities. Several nontransactivating IE1 mutants trans-dominantly interfered with wild-type IE1 transactivation of enhancer-linked DE genes. trans-dominant interference was expressed only by IE1 mutants that retained the N-terminal putative acidic activation domain, suggesting that this region may be involved in associations with a factor(s) essential for activation of enhancer-linked genes. PMID- 1433525 TI - Pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of CD4+ T cells. AB - In previous studies, it was observed that children immunized with a formalin inactivated respiratory syncytial virus vaccine (FI-RSV) developed severe pulmonary disease with greater frequency during subsequent natural RSV infection than did controls. During earlier efforts to develop an animal model of this phenomenon, enhanced pulmonary histopathology was observed after intranasal RSV challenge of FI-RSV-immunized cotton rats. Progress in understanding the immunologic basis for these observations has been hampered by the lack of reagents useful in manipulating the immune response of the cotton rat. This problem prompted us to reinvestigate the characteristics of immunity to RSV in the mouse. In the present studies, extensive pulmonary histopathology was observed in FI-RSV-immunized or RSV-infected BALB/c mice upon RSV challenge, and studies to determine the relative contributions of CD4+ or CD8+ T cells to this process were undertaken. Mice previously immunized with FI-RSV or infected with RSV were depleted of CD4+, CD8+, or both T-cell subsets immediately prior to RSV challenge, and the magnitude of inflammatory cell infiltration around bronchioles and pulmonary blood vessels and into alveolar spaces was quantified. The magnitude of infiltration at each anatomic site in previously FI-RSV-immunized or RSV-infected, nondepleted animals was similar, indicating that this is not a relevant model for enhanced disease. However, the effect of T-cell subset depletion on pulmonary histopathology following RSV challenge was very different between the two groups. Depletion of CD4+ T cells completely abrogated pulmonary histopathology in FI-RSV-immunized mice, whereas it had a much smaller effect on mice previously infected with RSV. FI-RSV-immunized or RSV-infected animals depleted of CD8+ T cells had only a modest reduction of pulmonary histopathology. In addition, RSV infection induced high levels of major histocompatibility complex class I-restricted cytotoxic T-cell activity, whereas FI-RSV immunization induced a low level. These data indicate that immunization with FI-RSV induces a cellular immune response different from that induced by RSV infection, which likely played a role in enhanced disease observed in infants and children. PMID- 1433526 TI - Human immunodeficiency virus type 1 Rev activation can be achieved without Rev responsive element RNA if Rev is directed to the target as a Rev/MS2 fusion protein which tethers the MS2 operator RNA. AB - The posttranscriptional trans activation of unspliced or partially spliced human immunodeficiency virus RNAs by the Rev regulatory protein is crucial for virus replication and is dependent on sequence-specific RNA binding by Rev. The cognate RNA target of Rev is contained within a highly structured, 244-nucleotide Rev responsive element (RRE) RNA in the viral env gene. Here, we show that specific interaction with the RRE is not an absolute requirement for Rev function. When the RRE is replaced by a heterologous MS2 phage operator sequence, Rev will facilitate the cytoplasmic expression of human immunodeficiency virus mRNAs containing this sequence if directed to the MS2 operator via the RNA binding motif of the MS2 phage coat protein (MS-C) as a Rev/MS-C fusion protein. Rev/MS-C efficiently activated both RRE and MS2 targets. A mutation in the MS2 operator that abolished the coat protein binding in vitro rendered the mutant RNA nonresponsive to the fusion protein in vivo. Notwithstanding that Rev can be tethered to the viral RNAs via another RNA binding motif, the structural integrity of the N terminus of Rev was still required for optimal trans activation. PMID- 1433527 TI - An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. AB - We isolated and molecularly cloned a human immunodeficiency virus type 1 (HIV-1) strain (89.6) which is unusual because it is both macrophage-tropic and extremely cytopathic in lymphocytes. Moreover, this is the first well-characterized infectious molecularly cloned macrophage-tropic HIV-1 strain derived from peripheral blood. HIV-1 89.6 differs markedly from other macrophage-tropic isolates within the envelope V3 region, which is important in determining cell tropism and cytopathicity. HIV-1 89.6 may thus represent a transitional isolate between noncytopathic macrophage-tropic viruses and cytopathic lymphocyte-tropic viruses. PMID- 1433528 TI - TAR-independent replication of human immunodeficiency virus type 1 in glial cells. AB - The molecular mechanisms involved in the replication of human immunodeficiency virus type 1 (HIV-1) may differ in various cell types and with various exogenous stimuli. Astrocytic glial cells, which can support HIV-1 replication in cell cultures and may be infected in vivo, are demonstrated to provide a cellular milieu in which TAR mutant HIV-1 viruses may replicate. Using transfections of various TAR mutant HIV-1 proviral constructs, we demonstrate TAR-independent replication in unstimulated astrocytic cells. We further demonstrate, using viral constructs with mutations in the tat gene and in the nuclear factor kappa B (NF kappa B)-binding sites (enhancer) of the HIV-1 long terminal repeat, that TAR independent HIV-1 replication in astrocytic cells requires both intact NF-kappa B moiety-binding motifs in the HIV-1 long terminal repeat and Tat expression. We measured HIV-1 p24 antigen production, syncytium formation, and levels and patterns of viral RNA expression by Northern (RNA) blotting to characterize TAR independent HIV-1 expression in astrocytic glial cells. This alternative regulatory pathway of TAR-independent, Tat-responsive viral production may be important in certain cell types for therapies which seek to perturb Tat-TAR binding as a strategy to interrupt the viral lytic cycle. PMID- 1433529 TI - Neutralization of diverse human immunodeficiency virus type 1 variants by an anti V3 human monoclonal antibody. AB - The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is thought to induce potent neutralizing antibodies which are generally defined as type specific and reactive with individual viral isolates. In contrast, the CD4 binding domain is thought to induce neutralizing antibodies that are group specific and capable of neutralizing all isolates of HIV-1. However, in this study, we used a panel of human monoclonal antibodies to these regions of gp120 which displays specificities and neutralizing activities that challenge these tenets. In particular, we used a human monoclonal antibody to the V3 domain with exceptionally potent and broad neutralizing activity against many diverse HIV-1 isolates. The anti-CD4-binding domain antibodies, on the other hand, showed a more restricted pattern of activity. PMID- 1433530 TI - Processing and localization of Dengue virus type 2 polyprotein precursor NS3-NS4A NS4B-NS5. AB - Processing of dengue virus type 2 polyprotein precursor NS3-NS4A-NS4B-NS5 could be mediated by the catalytically active NS3 protease domain and NS2B in trans at the dibasic sites NS3-NS4A and NS4B-NS5. Subcellular localization of the unprocessed precursor NS3-NS4A-NS4B-NS5 showed that it was confined to a distinct subcellular organelle in the cytoplasm, which was distinct from the distribution of the mature NS5. PMID- 1433531 TI - Specific binding of the human T-cell leukemia virus type I Rex protein to a short RNA sequence located within the Rex-response element. AB - Expression of the structural proteins of human T-cell leukemia virus type I is dependent upon the interaction of the viral Rex trans activator with its highly structured cis-acting RNA target sequence, the 254-nucleotide Rex-response element. Nucleotides critical for Rex binding in vitro have been mapped by modification interference analysis to a discrete 12-nucleotide RNA sequence that is predicted to form a stem-bulge-stem structure. This minimal RNA binding site was sufficient to mediate specific Rex binding in vitro when analyzed in the context of a short RNA probe. The critical importance of this short RNA sequence in mediating Rex function in vivo is supported by its complete conservation among all primate T-cell leukemia virus isolates. PMID- 1433532 TI - Effects of altering palmitylation sites on biosynthesis and function of the influenza virus hemagglutinin. AB - Mutagenesis studies indicated that the three cytoplasmic cysteines of the influenza virus A/Japan/305/57 hemagglutinin (HA) are all palmitylated, but to an unequal extent. Replacement of all three cysteines abolished palmitylation, but affected neither HA biosynthesis nor function. Palmitate was not required for HA to be incorporated into virions. PMID- 1433533 TI - The use of alloplastic biomaterials in bladder substitution. PMID- 1433534 TI - Renal colic in pregnancy. AB - Renal calculi are an infrequent but significant management problem during pregnancy. We reviewed all cases of renal colic occurring during pregnancy between 1979 and 1990 at Grace Hospital, a tertiary care obstetrical hospital in Vancouver, British Columbia. Of the patients 80 had a discharge diagnosis of renal colic and pregnancy during this 11-year period. Calculi were confirmed in 57 patients. Of the patients 66% were multiparous and 99% of the calculi occurred during either the second or third trimester. The most common symptom was flank pain seen in 89% of the patients, while greater than 95% displayed either microscopic or gross hematuria. Methods of radiographic diagnosis included ultrasonography and limited stage excretory urography. A total of 84% of patients passed stones spontaneously. Indications for urological or obstetrical intervention included persistent pain, sepsis, progressive hydronephrosis, solitary kidney or high grade obstruction. There were 37 procedures done in 23 patients. The most common procedure was placement of a ureteral stent. The complication rate associated with intrapartum intervention and stent passage in the 23 patients was 16%. All patients with a ureteral stent subsequently had spontaneous vaginal delivery without complication. A scheme for managing renal calculi in pregnancy is presented. PMID- 1433535 TI - Intraoperative sonography of renal tumors. AB - Intraoperative sonography (7.5 MHz. transducer with Doppler probe) was used to evaluate renal masses in 41 kidneys to determine its correlation with pathological findings. This intraoperative determination of the extent of the renal lesion prompted occasional changes in surgical management. We conclude that intraoperative sonography is most useful in partial nephrectomy, and helps to determine the extent of tumor, multicentricity, venous extension and associated cysts. These findings may not be appreciated with intraoperative, visual inspection of the kidney. PMID- 1433536 TI - Clean intermittent catheterization and urinary diversion in the management of renal transplant recipients with lower urinary tract dysfunction. AB - Renal transplant recipients with lower urinary tract dysfunction may be managed by urinary diversion or clean intermittent catheterization. To evaluate the comparative problems associated with each mode of therapy we studied 13 patients managed by clean intermittent catheterization (group 1, 6 patients) or urinary diversion (group 2, 7 patients). All 6 and 2 of 7 recipients in groups 1 and 2, respectively, had a neuropathic bladder. Mean followup was 3.7 +/- 1.5 (group 1) and 5.7 +/- 4.9 (group 2) years. Three allografts were lost in group 2 due to rejection (2) and death (1). Two patients each in groups 1 and 2 had febrile urinary tract infections requiring hospitalization and intravenous antibiotics. Complications related to urinary diversion developed in 4 patients in group 2. The serum creatinine at 1 and 3 years, number of hospital days per patient, total number of rejection episodes and number of patients employed in a full-time job following transplantation were similar in both groups. In summary, clean intermittent catheterization appears to have more morbidity in immunosuppressed transplant versus nontransplant patients but it may be preferable in renal transplant recipients due to the overall simplicity, positive psychological effect and comparable morbidity to other forms of management. PMID- 1433537 TI - Complications of radical cystectomy and urinary diversion: a retrospective review of 675 cases in 2 decades. AB - A retrospective review was performed on all 675 patients who underwent radical cystectomy and urinary diversion during 2 decades. Of the patients 197 were treated from 1969 to 1979 (group 1) and 478 were treated from 1980 until 1990 (group 2). The mean age of patients in group 1 was 56.7 years versus 64.2 years in group 2 (p < 0.001). The overall operative mortality rate in both groups was 2.5%. A total of 215 patients (31.9%) experienced postoperative complications (within 30 days of surgery). The morbidity rate was nearly identical between the 2 groups (32.0% for group 1 versus 31.8% for group 2, p = 0.962). Of note, however, there was a decreased incidence of wound infections and wound dehiscence among the patients in group 2 compared to group 1. Long-term complications occurred in 198 of the 675 patients (29.3%). At followup group 1 had a 35.5% incidence of long-term complications versus 26.8% in group 2 (p = 0.022). Most notably there was significant improvement in the incidence of ureteroenteric anastomotic strictures when comparing groups 1 (11.2%) and 2 (5.2%) (p = 0.006). PMID- 1433538 TI - Tamm-Horsfall protein as a marker in interstitial cystitis. AB - It has been suggested that immunohistochemical staining for Tamm-Horsfall protein in bladder epithelium may be a marker for interstitial cystitis. Of bladder biopsies from 14 interstitial cystitis patients only 3 demonstrated positive staining for Tamm-Horsfall protein within the mucosa, whereas 2 of 11 control biopsies showed positive Tamm-Horsfall protein results. In addition, staining in 4 ureteral specimens from interstitial cystitis patients and 4 controls was negative in all cases. An effort to detect this protein in enterocystoplasty specimens also showed a negative pattern. Our study does not confirm the Tamm Horsfall protein as permeating either the bladder epithelium in interstitial cystitis or bowel mucosa in enterocystoplasty. This finding does not necessarily mean that these surfaces are not permeable to substances of smaller molecular size, nor does it define whether this is of importance in the etiology of interstitial cystitis. However, it does suggest that this technique does not allow detection of a marker for the disease. PMID- 1433539 TI - Idiopathic reduced bladder storage versus interstitial cystitis. AB - Idiopathic reduced bladder storage is a term we used to describe a group of patients who have subjective and objective evidence (by cystometrogram) of diminished bladder capacity without a demonstrable cause. We performed a prospective study comparing this condition with interstitial cystitis. We studied the clinical, urodynamic and histological features, and response to therapy in these 2 groups of patients. No statistical difference was found between the incidence of irritative bladder symptoms and/or suprapubic pain. Only minor differences were noted in the maximum cystometric capacity and incidence of bladder instability. Histological and immunofluorescent features were analogous. Also, the reduced bladder storage and interstitial cystitis patients responded similarly to bladder dilation and pharmacological therapy. Augmentation ileocystoplasty used in patients refractory to medical treatment produced comparable results in the short term. Based upon similar findings, it is likely that these 2 conditions represent the same disease entity with the only difference being the cystoscopic findings. PMID- 1433540 TI - Treated history of noninvasive grade 1 transitional cell carcinoma. The National Bladder Cancer Group. AB - A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p < 0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone. PMID- 1433541 TI - Prognostic significance of mucosal aneuploidy in stage Ta/T1 grade 3 carcinoma of the bladder. AB - In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma. Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox's proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma. PMID- 1433542 TI - The value of immediate or early catheterization of the traumatized posterior urethra. AB - A total of 16 patients with posterior urethral ruptures was treated with the aim of reestablishing urethral continuity immediately or early after injury. Followup ranged from 13 to 83 months (average 27). In all patients an emergency retrograde urethrogram demonstrated extravasation from the posterior urethra. Of the patients 13 were treated with a urethral catheter either immediately or within 1 to 5 weeks after injury. Three patients were treated with a suprapubic catheter alone after unsuccessful attempts at reestablishing urethral continuity and all 3 subsequently required urethroplasty for an obliterative stricture. These 3 patients were also impotent after injury. Of the 13 patients treated with a urethral catheter 8 had the catheter inserted either retrograde (2) in the emergency room or antegrade (6) in the operating room just after the injury, and in 5 the catheter was inserted transurethrally at cystoscopy within a mean of 3 weeks after injury. A total of 7 patients (54%) treated with urethral catheterization had a stricture during followup: 4 responded well to internal urethrotomy and 3 required simple dilation. Of 12 patients 5 (42%) became impotent after injury, while 1 was impotent before injury. No patient became incontinent. We conclude that careful urethral catheter realignment either immediately or within 5 weeks after injury is safe and obviates total urethral closure. Impotence may result from the severity of the injury and not from management with catheterization. PMID- 1433543 TI - Penile extensibility: to what is it related? AB - Penile extensibility is the difference between the length of the flaccid penis and the penis submitted to a maximal constant traction. This measurement has been proposed for use as a new potential diagnostic method to assess intracavernous fibrosis. To determine the value of this method we measured penile extensibility before and after removing the skin and cavernous tissue in 17 cadavers and 4 patients undergoing penile implantation. In all cases a cavernous tissue biopsy was performed and the percentages of the different structures were objectively quantified by computer analysis. The extensibility decreased with patient age but it was not influenced by removal of the skin and/or cavernous tissue. No correlation was observed between decreased extensibility and the increase in fibrotic elements in the penile tissue. Penile extensibility seems to reflect the elasticity of the tunica albuginea, which is the limiting factor and cannot be an expression of fibrosis of the corpora cavernosa. PMID- 1433544 TI - Vascular impotence: focal or diffuse penile disease. AB - Using computerized image analysis the percentage of smooth muscle fibers was measured in several biopsies of the penis from 10 cadavers and 5 patients with vascular impotence. No significant difference was observed between the proximal and distal areas, and/or between the peripheral and central areas in 1 corpus cavernosum, and between the 2 corpora cavernosa for each patient or cadaver. The percentage of smooth muscle fibers was less in impotent patients in comparison with the cadavers, in which the erectile status was not known, and this reduction occurred throughout both cavernous bodies. Vascular impotence is a diffuse penile disease. Therefore, a cavernous body biopsy can be used to study the penile structure in the assessment of vascular impotence. PMID- 1433545 TI - Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction. AB - Recent experimental studies showed an important role of endothelium derived relaxing factor for cavernous smooth muscle relaxation. Since nitric oxide seems to account for the biological actions of endothelium derived relaxing factor, a study was done to examine a possible role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the treatment of erectile dysfunction. To determine a therapeutically useful dose 0.1, 0.2, 0.5 and 1 mg. SIN-1 were injected intracavernously in patients with erectile dysfunction. Each dose was given to 2 patients. Then, 63 patients received 1 mg. SIN-1, including 7 who had prolonged erections to minimal doses of papaverine plus phentolamine and 4 who did not respond with a full erection to other pharmacological agents. Intracavernous injection of SIN-1 induced a dose-dependent erectile response by increasing the arterial inflow and relaxing cavernous smooth muscles. Of the patients 29 had a full, 21 an almost full and 13 a moderate erection to 1 mg. SIN-1. There were no systemic or local side effects. In the patients with prolonged erections to papaverine plus phentolamine the mean duration of a full erectile response to SIN 1 was 57 minutes. Compared to the responses to a papaverine (15 mg./ml.) and phentolamine (0.5 mg./ml.) mixture, the erection induced by SIN-1 was superior in 10, comparable in 47 and inferior in 6 patients. Our data suggest a possible role for SIN-1 in the treatment of erectile dysfunction. Possible advantages may be that erection is induced by a mechanism similar to that occurring physiologically, a decreased risk of inducing prolonged erections and low therapy costs. PMID- 1433546 TI - Volume-dependent intracavernous hemodilution during pharmacologically induced penile erections. AB - The change in the cavernous hematocrit following induction of pharmacological erection by an intracavernous injection of papaverine hydrochloride was documented in normal controls and patients with impotence. Blood samples taken from the penile cavernosa showed a significantly lower hematocrit compared to the systemic venous blood in all normal subjects. The decrease in the cavernous hematocrit was attributable to dilution of the cavernous blood pool by the injected volume of the drug, since this was not observed in erections produced by visual sexual stimulation. It appears that a restriction of the cavernous venous outflow in response to papaverine injection causes sequestration of the diluted blood in the cavernous compartment. The degree of cavernous hemodilution was found to aid in the differential diagnosis and was especially valuable in differentiating patients with arteriogenic impotence from those with venous leakage. PMID- 1433547 TI - Early experience with the controlled girth and length expanding cylinder of the American Medical Systems Ultrex penile prosthesis. AB - A prospective study was done to evaluate length expansion characteristics of the AMS Ultrex penile prosthesis cylinder intraoperatively and in the early postoperative period. A total of 50 patients 30 to 74 years old (mean age 55.2 years) underwent implantation of this device. Intraoperative changes in the pubis to mid glans distance between deflation and inflation ranged from 1 to 4 cm. (mean 1.9). Postoperative followup measurements were obtained in 46 patients at 1 to 15 months (mean 4). There was a 1 cm. decrease in the amount of postoperative length expansion for 6 patients, while length expansion increased by 1 cm. for 12 and for 28 the postoperative length expansion was the same as the intraoperative length expansion. PMID- 1433548 TI - Varicocele treatment: prospective randomized trial of 3 methods. AB - This study was done to evaluate the surgical results and the impact on fertility potential of 3 methods of varicocele treatment. Consecutive varicocele patients with primary or secondary infertility were randomly assigned to 3 treatment groups. Of the patients 36 underwent percutaneous embolization, 55 high ligation of the internal spermatic vein and 28 transinguinal simultaneous ligation of the internal and external spermatic veins. The transinguinal ligation proved to be safe. There was no difference in pregnancy rates but the seminal variables showed a slight improvement with statistical significance only in the 2 open surgical methods. There were no surgical failures in the transinguinal group as opposed to the other 2 techniques. Transinguinal ligation of the internal and external spermatic veins may be recommended as the primary treatment for varicocele. This technique also seems to be the procedure of choice when repeat intervention is required for failure of high ligation or embolization. PMID- 1433549 TI - A test for the identification of relevant sympathetic nerve fibers during nerve sparing retroperitoneal lymphadenectomy. AB - We present a new intraoperative test for the identification of sympathetic nerve fibers relevant to ejaculation during nerve sparing retroperitoneal lymphadenectomy in patients with nonseminomatous testicular tumors. Electrostimulation of specific isolated postganglionic nerve fibers resulted in intraoperative ejaculation in 9 of 11 patients. Ejaculation was without tumescence in a noneruptive manner and was reproducible in most cases upon repeated stimulation. In 6 patients ejaculation resulted after stimulation of the L3 fiber and in 1 each after stimulation of the L1, L2 and hypogastric plexus. The test seems to be particularly useful in post-chemotherapeutic dissections or otherwise extended dissections when sparing of irrelevant fibers is to be avoided. PMID- 1433550 TI - Transurethral surgery using intravesical bupivacaine and intravenous sedation. AB - We report our experience using intravesical 0.5% bupivacaine as a topical anesthetic along with intravenous fentanyl and midazolam sedation to perform a variety of transurethral procedures in 78 patients. We achieved adequate pain control in all patients and observed no anesthetic complications. Use of this combination of intravesical topical anesthesia and intravenous sedation provided safe, adequate anesthesia to our patients undergoing various transurethral procedures in an outpatient clinic setting. PMID- 1433551 TI - Ambulatory monitoring of bladder pressure in low compliance neurogenic bladder dysfunction. AB - Upper tract dilatation is an important complication of neurogenic bladder dysfunction. Risk factors include incomplete bladder emptying with large residual volumes of urine and high tonic increases in bladder pressures during artificial filling. However, on natural bladder filling many of these patients do not have high tonic increases in detrusor pressures. We compared conventional urodynamic studies with ambulatory monitoring during natural bladder filling in 66 patients with low compliance neurogenic bladder dysfunction. There were marked differences in the tonic increase in bladder pressure during filling and in compliance during artificial bladder filling compared with ambulatory monitoring. Faster filling rates during artificial filling resulted in greater end filling pressures and lower compliance but the lowest increases in bladder pressure were found during ambulatory monitoring with natural bladder filling. During natural bladder filling significantly more patients had phasic changes in detrusor pressure; a high intensity of phasic activity during ambulatory monitoring correlated with high end filling pressures during artificial bladder filling. Upper tract dilatation was associated with large volumes of residual urine, high resting bladder pressures and low bladder compliance on filling at 100 ml. per minute. However, upper tract dilatation was most strongly associated with high intensity phasic pressure activity during natural bladder filling in combination with high residual urine volumes and high resting bladder pressures. On multivariate statistical analysis the intensity of phasic pressure activity during ambulatory monitoring was the best discriminator between patients with dilated and normal upper tracts. Our study has highlighted important differences in the results obtained by artificial filling cystometry and ambulatory monitoring during natural bladder filling. In particular, high increases in pressure did not occur during natural bladder filling, apparently being replaced by phasic activity. Within this group of patients who had the high risk factor of low bladder compliance measured during artificial bladder filling, a combination of greater residual urine volumes, greater resting pressures and greater phasic activity during natural bladder filling was found in patients with upper tract dilatation. PMID- 1433552 TI - A quantitative histological analysis of the dilated ureter of childhood. AB - A quantitative histological study of the dilated ureter of childhood was performed on 26 ureters. The specimens were from 15 male and 11 female patients 10 days to 12 years old (mean age 2.0 years). A color image analysis system was used to examine and compare collagen and smooth muscle components of the muscularis layers to normal control ureters of similar age. In comparing primary obstructed (12) to primary refluxing (14) megaureters and control ureters (6), there was a statistically different collagen-to-smooth muscle ratio (p < 0.001) between the primary obstructed and primary refluxing megaureter groups. For patients with primary refluxing megaureter there was a 2-fold increase in the tissue matrix ratio of collagen-to-smooth muscle when compared to patients with primary obstructed megaureter. In the primary obstructed megaureters the amount of collagen and smooth muscle was not statistically different from controls (p > 0.01). The increased tissue matrix ratio of 2.0 +/- 0.35 (collagen-to-smooth muscle) in the refluxing megaureter group compared to 0.78 +/- 0.22 in the obstructed megaureter group and 0.52 +/- 0.12 in controls was found to be due not only to a marked increase in collagen but also a significant decrease in the smooth muscle component of the tissue. Primary obstructed and normal control ureters had similar quantitative amounts of smooth muscle with 60 +/- 5% and 61 +/- 6%, respectively, while refluxing megaureters had only 40 +/- 5% smooth muscle. The percentage collagen was 36 +/- 5 in the obstructed megaureter group and 30 +/- 5 in controls, with refluxing megaureters having 58 +/- 5% collagen on analysis. Our findings emphasize the significant differences in the structural components (collagen and smooth muscle) of the dilated ureter of childhood, and provide us with further insight into the pathological nature of these dilated ureters and their surgical repair. PMID- 1433553 TI - Prenatal diagnosis of the megacystis-megaureter association. AB - A total of 11 male neonates with hydronephrosis and a large bladder in utero had the megacystis-megaureter association. Prenatal ultrasound findings included bilateral hydroureteronephrosis; a large, smooth, thin-walled bladder, and normal volume of amniotic fluid. Postnatal studies demonstrated grades 4 to 5 bilateral reflux, a large bladder without obstruction and in 2 infants nonfunction of a kidney or renal moiety. Of 7 infants initially managed nonoperatively 5 have undergone surgery due to persistent reflux or breakthrough urinary infections. The prenatal diagnosis of the megacystis-megaureter association can be suspected with reasonable accuracy. Prompt postnatal continuous antibiotic prophylaxis and uroradiological confirmation allow for nonemergency management of this condition with excellent results. PMID- 1433554 TI - Endopyelotomy associated ureteral necrosis: complete ureteral replacement using the Boari flap. AB - A case of an adolescent who sustained necrosis of the entire ureter after attempted endopyelotomy for congenital ureteropelvic junction obstruction is presented. Successful reconstruction of a neoureter was performed easily with the Boari bladder flap coupled with nephropexy and a psoas hitch. Although repair of upper ureteral injuries with the Boari flap has been described in the literature, to our knowledge its use in the pediatric population has not. Our case exemplifies how the Boari flap repair is particularly suitable in children for bridging significant segments of injured ureters, not just the lower third. PMID- 1433555 TI - Influence of preoperative bladder capacity and compliance on the outcome of artificial sphincter implantation in patients with neurogenic sphincter incompetence. AB - We performed a retrospective study of 23 patients with neurogenic sphincteric incompetence who had undergone implantation of an artificial urinary sphincter to determine if bladder capacity and compliance as determined by cystometrography could predict the need for enterocystoplasty. Study criteria were neurogenic sphincteric incompetence, no previous operations on the lower urinary tract, and performance of preoperative and postoperative cystometrography. Patients were 5 to 17 years old at implantation. Incontinence was caused by myelomeningocele (18 patients), sacral agenesis (3) and spinal cord tumor (2). The 8 patients for whom preoperative cystometric bladder capacity was greater than 60% of the expected capacity for age have been followed for a mean of 60 months. All 8 patients are continent and none required enterocystoplasty. Preoperative bladder compliance exceeded 2 ml./cm. water in all patients (group 1). Of the 15 patients for whom preoperative cystometric bladder capacity was less than 60% of the expected value (group 2, small bladders) 8 followed an average of 72 months had a compliance greater than 2 ml./cm. water and have done well without bladder augmentation. In contrast, 7 patients in this group (46%) required enterocystoplasty: 6 for persistent or recurrent incontinence and 1 for upper tract changes. The average interval between artificial sphincter placement and enterocystoplasty was 14 months. Patients with a small bladder that required augmentation had a preoperative bladder compliance of less than 2 ml./cm. water. We conclude that small bladder capacity, as determined by cystometrography in patients with neurogenic sphincteric incompetence but a bladder compliance of less than 2 ml./cm. water predicts the future need for bladder augmentation. In all other patients, with good medical treatment and followup, the possible adverse effects of a small capacity bladder can be prevented or corrected. With this strategy we have been able to avoid enterocystoplasty with its attending potential complications in 70% of our patients with neurogenic incontinence and favorable urodynamics regardless of preoperative cystometric bladder capacity. PMID- 1433556 TI - Adventitious knots in urethral catheters: report of 5 cases. AB - Urethral catheterization with 5 or 8F feeding tubes in 5 boys was complicated by stochastic knotting within the bladder thereby impeding removal. The common factor in these patients was insertion of excessive length within the bladder. Percutaneous endoscopic retrieval was done successfully in 1 child. This technique may avoid urethral trauma associated with catheter removal, particularly in younger boys. PMID- 1433557 TI - Radiographic and serologic correlates of azotemia in patients with posterior urethral valves. AB - A retrospective statistical analysis with a minimum followup of 10 years was done on 102 patients who presented in early childhood with posterior urethral valves. All patients were treated with initial bladder drainage. Factors correlating with the development of renal failure were evaluated. No patient with a normal kidney on 1 side had renal failure. Calculated glomerular filtration rate was significantly higher in patients who retained adequate renal function (80.7 +/- 17.8 ml. per minute per 1.73 m.2), as compared with those who had renal failure (18.6 +/- 9.6 ml. per minute per 1.73 m.2). Patients with renal failure also had a significantly higher serum creatinine level at stabilization (2.0 +/- 0.8 mg./dl.) than those who had adequate renal function (0.5 +/- 0.2 mg./dl.). The presence of bilateral high grade vesicoureteral reflux, hydronephrosis and nonfunction was significantly higher in patients with renal failure. Patient age at presentation was not a significant factor. These data represent a guideline for the prognosis and management protocols of infants with dilated upper urinary tracts and posterior urethral valves. PMID- 1433558 TI - Urethral stricture in children: treatment by urethroplasty with bladder mucosa graft. AB - Urethral strictures in children, which are not frequent, often require urethroplasty when dilations and/ or urethrotomies have failed. A bladder mucosa graft was used successfully for urethral reconstruction to treat posterior hypospadias. We describe our experience with a bladder mucosa graft during urethroplasty for acquired urethral strictures in 8 children. Urethral strictures secondary to the treatment of hypospadias were excluded. Bladder mucosa was used successfully as an onlay or patch graft urethroplasty in 7 patients. One patient had a tubularized graft with secondary stenosis treated successfully by dilation. PMID- 1433559 TI - Onlay island flap urethroplasty: variation on a theme. AB - The onlay island flap urethroplasty is useful in patients with distal, mid shaft and proximal hypospadias who have a well developed urethral plate and exhibit little or no curvature after release of chordee. The technique described has 2 main features: 1) use of the entire inner prepuce of the foreskin facilitates its mobilization and protects the vascular pedicle, and 2) additional soft tissue coverage is gained by removing the excess preputial mucosa not used for the neourethra. This extra soft tissue covering of the suture lines should prevent fistula formation. During the last 4 1/2 years the onlay island flap has been used for repair of hypospadias in 61 patients. The complication rate (6%) is low and compares favorably with other techniques. Further refinements in the onlay flap hypospadias repair should decrease the complication rate and widen its applicability. PMID- 1433560 TI - Penoscrotal transposition with hypospadias: 1-stage repair. AB - A 1-stage surgical repair of penoscrotal transposition with hypospadias is described. The basic principles are correction of hypospadias with the best vascularized island penile skin flap used for a new urethra and 2 vascularized sliding skin flaps used for reconstruction of the penile skin, and transposition of the penis to the suprascrotal position in the area of the mons pubis, with mobilization plus midline testicular fixation (inter-orchiopexy) and scrotoplasty. This technique was applied in 42 patients 2 to 9 years old between 1986 and 1991. The complications were 2 urethral stenoses on the proximal anastomosis (1 was treated successfully by urethrotomy and 1 by an open operation) and 2 fistulas (successfully treated by surgery), while 2 patients required additional correction of penoscrotal transposition. PMID- 1433561 TI - Intraoperative spermatic venography during varicocele surgery in adolescents. AB - Intraoperative internal spermatic venography performed immediately following varicocele ligation in the adolescent has been touted as reducing varicocele persistence rates. Previously published data corroborate this statement with low persistence rates. Other series in which venography was not performed report a failure rate of 9 to 30%. During a 5-year period a total of 64 varicocele ligations was performed in 62 male adolescents at our institution. Followup postoperatively revealed an overall varicocele persistence rate of 9%. All patients had intraoperative internal spermatic venography on the affected side. Of 64 venograms 16% had shown collateral drainage that, if not ligated, may have resulted in varicocele persistence. These cases accounted for only 1 of the persistent varicoceles. Additionally, venograms had demonstrated filling of the ipsilateral external iliac vein in 8% of the cases. Despite the fact that no attempt was made to ligate these collaterals, none of these patients had a persistent varicocele. After varicocele ligation 30 of 62 patients were followed long enough to evaluate for testicular catch up growth. Of these 30 patients 24 demonstrated an average relative increase in left testicular volume of 17%. These data support routine intraoperative internal spermatic venography while performing varicocele ligation in the adolescent. PMID- 1433562 TI - Endocytosis of calcium oxalate crystals and proliferation of renal tubular epithelial cells in a patient with type 1 primary hyperoxaluria. AB - A patient with primary hyperoxaluria who received a liver-kidney transplant is presented. A postoperative renal biopsy showed apparent tubular cell endocytosis of calcium oxalate crystals and cell proliferation, indicating that renal epithelial cells do not perceive urinary crystals as inert. Such cellular responses to crystals may have a role in nephrolithiasis. PMID- 1433563 TI - Arteriovenous fistula complicating endopyelotomy. AB - We report a case of arteriovenous fistula and pseudoaneurysm formation following endopyelotomy. Presentation, successful management with interventional radiology techniques, and the relationship between variant renal artery anatomy and endopyelotomy are discussed. PMID- 1433564 TI - Leiomyoma of the female urethra: a case report and review. PMID- 1433565 TI - The management of injuries to the urethra, bladder or vagina encountered during difficult placement of the artificial urinary sphincter in the female patient. AB - Between 1977 and 1989, an artificial urinary sphincter was implanted in 57 female patients. In 6 patients inadvertent intraoperative injuries to pelvic organs occurred, 5 of whom had a history of an average 2.8 previous operations for incontinence (range 2 to 4). The remaining patient was a 16-year-old girl with primary internal sphincter incompetence. All 6 patients presented with total incontinence. Intraoperative injury included 4 women who sustained vaginal perforations, while 1 had an anterior bladder perforation and in 1 the urethra was entered. Mechanisms of injury were sharp perforation of structures adherent to the pubis and blunt tears of distorted urethrovaginal tissues. Primary closures of the urethra, bladder and vaginal defects followed by insertion of the artificial urinary sphincter were accomplished successfully. Postoperative management included vaginal antiseptic packs, appropriate antibiotics and delayed sphincter activation. Of the 6 patients 5 remained dry after initial placement with a mean followup of 32 months (range 7 to 77). The remaining patient required replacement with a higher pressure balloon and a smaller cuff, which resulted in complete continence. PMID- 1433566 TI - Use of a polytetrafluoroethylene tube graft as a circumferential neotunica during placement of a penile prosthesis. AB - Various techniques have evolved for augmentation of the tunica albuginea in cases when tunical tissue has been found deficient during penile prosthesis implantation. An intraoperative situation occurred in which the size of the tunical defect did not permit primary tunical closure or allow for approximation by placement of a tunical patch graft. In this case, to ensure satisfactory insertion of a penile prosthesis a polytetrafluoroethylene (Gore-Tex) tube graft was used as a circumferential neotunica. PMID- 1433567 TI - Epididymo-orchitis developing as a late manifestation of intravesical bacillus Calmette-Guerin therapy and masquerading as a primary testicular malignancy: a report of 2 cases. AB - In 2 cases epididymo-orchitis, indistinguishable from a testicular tumor, developed as a late (15 and 34 months, respectively) complication following use of Tice strain bacillus Calmette-Guerin for treatment of superficial bladder carcinoma. In each instance the lesion was asymptomatic and ultrasonography demonstrated a complex scrotal mass. Inguinal orchiectomy was performed for diagnosis and therapy. The importance of obtaining a mycobacterial culture for further therapy planning is stressed. PMID- 1433568 TI - Prostatic abscess due to Candida tropicalis in a nonacquired immunodeficiency syndrome patient. AB - We report a case of prostatic abscess due to Candida tropicalis in a nonacquired immunodeficiency syndrome patient with diabetes. The diagnosis and management are discussed, and the literature is reviewed. PMID- 1433569 TI - Papillary adenocarcinoma in a seminal vesicle cyst associated with ipsilateral renal agenesis: a case report. AB - Cysts and tumors of the seminal vesicle are uncommon, and their coexistence is extremely rare. We report a case of multiple papillary tumors inside a seminal vesicle cyst associated with ipsilateral renal agenesis in a 17-year-old man. Surgical excision of the cyst and tumors was performed without any morbidity and histology revealed well differentiated papillary adenocarcinoma. PMID- 1433570 TI - Effect of PSK and its subfractions on peripheral blood lymphocytes mediated cytotoxicity against urinary bladder tumor cells. AB - Our previous studies have indicated that the protein-bound polysaccharide Kreha (PSK) enhances the cytotoxic activity of peripheral blood lymphocytes (PBL) against the T24 human urinary bladder tumor cell line in patients with bladder tumor. Since PSK consists of a mixture of various kinds of protein-bound polysaccharides, the present study was designed to examine which subfractions of PSK mediated the enhancement of cytotoxicity. When PSK was separated according to size, treatment of PBL with the 50 kilodalton (kd) or less fraction killed T24 cells more efficiently than unfractionated PSK-treated PBL. The higher molecular weight fractions did not enhance killing above the control level. PSK was fractionated on a diethylaminoethyl (DEAE)-cellulose column to obtain a protein rich fraction that absorbed onto the column and a polysaccharide rich fraction that did not. PBL treated with the polysaccharide rich fraction were able to kill T24 cells more effectively than unfractionated PSK-treated PBL. The protein rich fraction had no effect on the killing. Further fractionation of the polysaccharide rich fraction was performed by differential precipitation with ammonium sulfate. PBL treated with the precipitated fraction at 70-80% saturation (PSK Fraction D) enhanced cytotoxicity equal to that of the polysaccharide rich fraction. Treatment of PBL with the other fractions did not augment the cytotoxicity. These enhancement by PSK fractions were observed in healthy donors and also in patients with bladder tumor. An increase of the proliferative response of PBL to PSK Fraction D as well as unfractionated PSK was observed. Treatment of PBL with PSK Fraction D had no effect on the proportion of PBL binding to T24 cells, thus suggesting a post-binding effect. The structure of PSK Fraction D as inferred from the results of methylation analysis was mainly an alpha-glucan. These results demonstrate that PSK mediated enhancement of cytotoxicity and proliferation of PBL may be largely due to an alpha-glucan of less than 50 kd. PMID- 1433571 TI - Impaired immune response by isoniazid treatment during intravesical BCG administration in the guinea pig. AB - At present, isoniazid (INH) is being used prophylactically to reduce the side effects of intravesical BCG therapy for superficial bladder cancer, although it is not clear whether or not this reduces the antitumor efficacy of BCG. In this study the impact of INH treatment on the immune response after repeated intravesical BCG administration was investigated in guinea pigs. INH was given on the 3 days around each BCG instillation. We found that the administration of INH severely impaired the immunological effects of BCG. The induction of mononuclear cell infiltration in the bladder wall was reduced. Enlargement of the regional lymph nodes (weight and number of cells), and increase of MHC Class II expression on the lymph node cells, normally observed after intravesical BCG administration, were inhibited by INH. Systemic immunity, measured by the DTH reaction in the skin to PPD, was also diminished due to the combined treatment of BCG with INH. When INH was administered during the last 4 of 6 BCG instillations, the immune response to BCG was still impaired. A five-fold increase of the dose of BCG did not overcome the effect of INH. INH probably did not exert a direct suppression of the immune system of the guinea pig as the DNCB skin reactivity was not influenced. Although INH concentrations in the urine were high at the onset of the instillation, in vitro experiments indicated that the effect of INH may not be caused by killing of the BCG organisms shortly after application in the bladder. In conclusion, our data in guinea pigs suggest that the use of INH may impair the immune response to intravesical BCG. As this response may be important for the antitumor effect of BCG, urologists should be cautious with the prophylactic use of INH. The influence on the antitumor efficacy is now investigated in man. PMID- 1433572 TI - Expression of adhesion molecules by bladder cancer cells: modulation by interferon-gamma and tumour necrosis factor-alpha. AB - The constitutive expression by eight human bladder cancer cell lines of the cell adhesion molecules intercellular adhesion molecule-1 and intercellular adhesion molecule-2 was studied using monoclonal antibody probes in conjunction with flow cytometry. Tumour lines of low grade (G1) did not constitutively express intercellular adhesion molecule-1, rather they were found to express intercellular adhesion molecule-2. The G2 cells expressed no intercellular adhesion molecule-2, however, a low percentage did express intercellular adhesion molecule-1. High grade cells (G3) only expressed intercellular adhesion molecule 1 on their cell surface but at higher levels than the G2 cell line. Exposure of the bladder cancer cell lines to interferon-gamma induced and augmented the expression of intercellular adhesion molecule-1 by all except one of the cell lines (UMUC3). Intercellular adhesion molecule-2 expression remained unaltered. The modulation of intercellular adhesion molecule-1 expression was dependent on the concentration of interferon-gamma and the duration of stimulus. De novo intercellular adhesion molecule-1 expression, induced by interferon-gamma, was rapid (< 4 hours) with only a short period of stimulation being required (< 10 seconds). The rapid increase in expression of intercellular adhesion molecule-1 required de novo protein synthesis and was not the result of release of intercellular adhesion molecule-1 from an intracellular pool. Interferon-gamma and tumour necrosis factor-alpha were found to act synergistically in the induction and augmentation of intercellular adhesion molecule-1 expression. Optimal induction occurred with 10 Uml-1 of both molecules. These results suggest a correlation between constitutive adhesion molecule expression and the histopathological grade of the tumour. The implications of these findings for Bacillus Calmette Guerin and interferon-gamma immunotherapy of bladder cancer is discussed. PMID- 1433573 TI - Diabetes mellitus impairs neurogenic and endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. AB - The effect of alloxan-induced diabetes on the reactivity of corporeal nerves, endothelium and smooth muscle was studied in the New Zealand white rabbit. Fifteen rabbits were randomly divided into treated (n = 6) and control (n = 9) groups. The treated group was maintained for 6 weeks. Two control groups were studied. One control group (n = 3) was maintained for 6 weeks as littermate controls for diabetic group. The second control group (n = 6) was not maintained but was weight matched with the 6 week diabetic group. The reactivity of corpus cavernosum tissue from the diabetic animals and the control animals was studied in organ chambers. When tissue contraction was produced with phenylephrine for the study of relaxation to various stimuli, the tension induced was similar in the diabetic and the control groups. Relaxation of corpus cavernosum tissue to electrical stimulation of autonomic nerves as well as relaxation to the endothelium-dependent vasodilator acetylcholine were comparably unaffected in the weight matched and littermate control groups while significantly inhibited in the diabetic group. Treatment of the corporeal tissue with the cyclooxgenase inhibitor indomethacin enhanced the relaxation to electrical stimulation and to acetylcholine in the control and in the diabetic groups but did not improve the significant difference in relaxation between the two groups. Relaxation of corporeal tissue to endothelium-independent vasodilators, papaverine and nitroprusside was similar in the control groups and the diabetic groups. It is concluded that diabetes impairs neurogenic and endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. These findings are comparable to those described in corpus cavernosum tissue from diabetic men, showing the validity of this experimental animal model. The mechanism for the nerve or endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the ability of the corporeal smooth muscle to relax via a cGMP dependent mechanism. Since nitric oxide has been shown to act as the nonadrenergic noncholinergic neurotransmitter as well as endothelium-derived relaxing factor (EDRF) of the trabecular smooth muscle, it is possible that impairment of neurogenic and endothelium-dependent relaxation due to diabetes is mediated by alteration in the synthesis or availability of nitric oxide in corporeal tissue. PMID- 1433574 TI - Microbial adhesion and biofilm formation on ureteral stents in vitro and in vivo. AB - Thirty ureteral stents, inserted for 5 to 128 days following extracorporeal shock wave lithotripsy, were examined for the presence of bacterial biofilms. Of these, 90% had adherent pathogens (44% mixed organisms) on the stents, 45% of which were present in low numbers (10(1)-10(2) per 1 cm3 section) and 55% were in small and large microcolony biofilms (> 2 x 10(2)-10(7)). The organisms were recovered from the stents even though urine culture was only positive in 27% of patients. Of the organisms isolated, 77% were Gram positive cocci, 15% Gram negative rods and 8% Candida. No blockage of the stents occurred. All of the patients had received antimicrobial therapy post-insertion, and in 15 cases biofilms were found while on treatment. None of the patients received therapy for urinary tract infections while the stent remained in place. In vitro experiments demonstrated the ability of Escherichia coli, Proteus mirabilis, Staphylococcus epidermidis and Enterococcus faecalis uropathogens to adhere and form biofilms on ureteral stents within 24 hours. Clearly, bacterial biofilms do occur on ureteral stents and urinary culture may not detect their presence. The high recovery rate of Gram positive organisms may indicate a preferential adhesion to the biomaterial surface. The findings also indicate that unlike biofilm formation on many other prosthetic implants, colonization with Gram positive organisms on ureteral stents does not necessarily coincide with the development symptomatic infection. PMID- 1433575 TI - Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype. AB - Allelic loss of chromosome 17p with a mutated p53 gene on the remaining allele has been observed in various kinds of human cancers. To examine the significance of allelic loss of chromosome 17p in human urothelial cancer with special attention to the clinicopathological features, 49 tumors with various stages and grades from 43 cases (35 bladder cancers and 8 renal pelvic or ureteral cancers) were examined for loss of heterozygosity using 5 polymorphic probes on chromosome 17p. Thirty-seven cases were informative, and allelic loss of chromosome 17p was observed in 15 (41%) of them. In bladder cancers, the loss of 17p was observed with significantly higher frequency (p < 0.01) in cases with invasive (> or = pT2) tumors (7/10, 70%) than in cases with superficial (pTa or pT1) tumors (4/21, 19%). In renal pelvic or ureteral cancers, none of 2 superficial tumors and all of 4 invasive tumors showed the allelic loss. As to tumor grade, the allelic loss was observed in 1/9 (11%) for grade 1 cases, 6/18 (33%) for grade 2 cases, and 8/10 (80%) grade 3 cases (grade 1 versus 3, p < 0.01; grade 2 versus 3, p < 0.05). On the other hand, examination of clinical features, such as primary tumor site, tumor multiplicity or previous history of urothelial cancer did not significantly influence the frequency of the allelic loss. Our results suggest that the allelic loss of chromosome 17p is strongly associated with invasive phenotype in urothelial cancer. The results further indicate that the 17p deletion may represent a new genetic marker of malignant potentials in urothelial cancers. PMID- 1433576 TI - Urinary bladder function in the tight-skin mouse. AB - Tight-skin mice develop hypertrophy of connective tissue and tendons, associated with increases in collagen concentration in skin, heart, lungs, and tail. The bladders from these mice have not previously been examined. Because of the purported importance of collagen in bladder wall structure and compliance, we examined collagen content, micturition characteristics, and length-tension relationships in bladders from tight-skin mice. Bladder collagen content and concentration were approximately 70% greater in 5-6 month tight-skin mice than age-matched controls, but bladder mass, protein content, and protein concentration were similar. Tight-skin mice urinated larger volumes more frequently during the light cycle, and the functional bladder capacity appeared to be greater than that of controls. There was a small shift to the right of the passive length-tension curves of bladder strips from tight-skin mice, but the shift was not statistically significant. The magnitude of active tension development was the same. The data suggest that bladder collagen concentration does not necessarily determine bladder capacity or compliance. It is suggested that other factors, such as the ratio of collagen subtypes or the collagen:elastin ratio may have more importance for the maintenance of bladder distension. PMID- 1433577 TI - Comparison of urinary bladder function in 6 and 24 month male and female rats. AB - Micturition characteristics, collagen composition, and in vitro urinary bladder strip contractility were examined in young adult (six month) and old (24 month) male and female Fischer 344 rats. Although young female rats consumed significantly less water than young males, there were no differences in volumes of urine excreted. Old females excreted significantly more urine than old males, but there were no differences in volumes of water consumed. Old male rats had similar micturition frequencies during the light and dark cycles, in contrast to females and young males, where the number of micturitions during the dark cycle was significantly greater than those during the light cycle. The mean and maximal micturition volumes were significantly greater in old males compared to young males and old females during both the light and dark cycles. Bladders from female rats weighed significantly less than bladders from males of the same age, and the bladders from young rats weighed less than those of old rats. The protein and collagen concentrations were significantly less in bladder bodies from young females than old females. The amount of collagen resistant to digestion by Pronase, and thus thought to be cross-linked, was significantly greater in bladders from old rats compared to young. No differences between groups were found in the contractile responses of bladder base strips. There were trends for the absolute contractile responses of bladder body strips from old males to field stimulation, carbachol, ATP, and KCl to be larger than the other groups, and for strips from the young females to be smaller. The responses of strips from young females to field stimulation and KCl were significantly less than those of young males or old females, and responses to 10(-3) M ATP were less than those of old females. Responses of strips from old males to 60 mM KCl were significantly greater than those of young males. The differences in contractility could be attributed to the differences in strip mass. It appears, therefore, that urinary bladder function in male and female rats is unaffected by increasing age between 6 and 24 months. PMID- 1433578 TI - A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. PMID- 1433579 TI - The detection and characterization of vesicoureteral reflux in the child. AB - Voiding cystourethrography or radionuclide cystography should be performed in the child in whom it is important to know whether reflux is present. Voiding cystourethrography is more accurate in characterizing and grading reflux, and monitoring is intermittent. Conversely, radionuclide cystography uses a lower radiation dose and its continuous monitoring leads to fewer false negative results but its ability to characterize reflux is poor. The performance of voiding cystourethrography or radionuclide cystography to detect reflux is an art as well as a science. These tests are done best by those who are experienced and interested in imaging the urinary tract of the child. At our hospital we perform voiding cystourethrography in all young children with urinary tract infection to detect and precisely characterize reflux to enable intelligent planning of management. In older patients, when it is less likely that reflux is present but it is still desirable to ensure that reflux is not occurring, radionuclide cystography is performed. If reflux is present, then a decision is made on an individual basis as to whether additional characterization by voiding cystourethrography is needed. Radionuclide cystography is also used for family screening, for periodic followup of reflux being managed nonoperatively and to ensure that reflux has been eliminated after antireflux surgery. PMID- 1433580 TI - Characteristics at entry of children with severe primary vesicoureteral reflux recruited for a multicenter, international therapeutic trial comparing medical and surgical management. The International Reflux Study in Children. AB - A total of 532 children, 401 from Europe and 131 from the United States, was recruited into an international multicenter study comparing the results of medical and surgical treatment of children with international grade III or IV vesicoureteral reflux and urinary tract infection. Patient age was less than 11 years, glomerular filtration rate was greater than 70 ml. per minute per 1.73 m.2 and there was no obstruction, renal malformation, previous urinary tract surgery or neuropathic bladder. A total of 80 children had less than grade III vesicoureteral reflux on a second pre-entry cystourethrogram required by the European protocol, and they were followed separately as a sideline group. At entry the age distribution, history of urinary tract infection and proportion of children with grade IV vesicoureteral reflux were similar in Europe and the United States. Of the European and United States children 48% and 54% had renal scarring, and 17% and 14% had parenchymal thinning, respectively. In each group renal length and planimetric area were normal in two-thirds and 5% had small kidneys (<2 standard deviations from normal). Differences included sex distribution (24% boys in Europe and 11% in the United States group), the proportion of children in whom vesicoureteral reflux was previously known (18% Europe and 69% United States) and the proportion of children with bilateral reflux (77% Europe and 57% United States). Randomization and stratification for treatment were successful. PMID- 1433581 TI - Infection pattern in children with vesicoureteral reflux randomly allocated to operation or long-term antibacterial prophylaxis. The International Reflux Study in Children. AB - A total of 306 children with grade III to IV vesicoureteral reflux (international classification) and a history of documented urinary tract infection was randomized into medical (155 patients) or surgical (151 patients) treatment arms in the European portion of the International Reflux Study in Children. Children treated medically were maintained on prophylactic antibacterials as long as the reflux persisted, while those treated surgically were covered prophylactically until followup studies at 6 months postoperatively demonstrated the reflux to be corrected. Standard definitions for bacteriuria were used, and the distinction was made clinically among acute pyelonephritis, cystitis and asymptomatic bacteriuria, supported in many instances by additional laboratory testing. Urine was cultured after 3 months and whenever suspicious symptoms occurred. Urinary tract infections developed during the first 5-year followup period in 59 patients (38%) in the medical group and in 59 (39%) in the surgical group but the incidence of pyelonephritis was higher in the medical group (21%) than in the surgical group (10%) (p < 0.01). Pyelonephritis often followed catheterization or cystoscopy but asymptomatic bacteriuria was uncommon after these procedures in either group. Recurrent infections were related to age, sex and treatment center. They were common in boys and girls entering under 1 year of age but were less common in girls and rare in boys entering after 1 year of age. Recurrences were lowest among the Finnish children and highest in the German and Belgian children. PMID- 1433582 TI - Renal scars and parenchymal thinning in children with vesicoureteral reflux: a 5 year report of the International Reflux Study in Children (European branch). AB - A total of 321 children less than 11 years old with nonobstructive grade III or IV vesicoureteral reflux and with previous urinary tract infection was randomly allocated to medical or surgical treatment in the European branch of the International Reflux Study in Children. (Randomization was stratified for age, sex, grade of reflux, presence of renal scarring, interval since last urinary tract infection and treating hospital). The results of excretory urography are reported for 233 girls and 73 boys treated according to the random allocation, 89% of whom were followed for 5 years. After 5 years in the medical group (155 children) new renal scars were seen in 19 and new renal parenchymal thinning in 11. The proportions were almost identical among 151 children allocated to surgical treatment with 20 new scars and 15 new thinnings. Progression of established scars was also similar in both groups. However, the new scars developed sooner after surgery than during medical treatment. In 6 surgically treated children postoperative obstruction was followed by the development of new scars. In addition, 12 patients showed new scars approximately 6 months after successful surgery, while in only 2 children scars developed more than 6 months after surgery. In 11 children of the medical group new scars were seen more than 6 months after allocation. More new scars developed in the children with parenchymal thinning at entry (23%) than in those with scarred or normal kidneys at entry (10% each) (p < 0.05). The younger the patients at entry, the higher the frequency of new scars (less than 2 years 19.8%) 2 to 4 years 9.8% and 5 years or more 4.6%, p < 0.05). PMID- 1433583 TI - Surgical results in the International Reflux Study in Children (Europe). AB - In the European part of the International Reflux Study in Children (7 participating centers) 151 infants and children were randomly allocated to surgical treatment of primary grades III and IV vesicoureteral reflux. Reimplantation was performed unilaterally in 65 patients and bilaterally in 86, for a total of 237 ureters reimplanted. The patients were followed at regular intervals for 5 years. Reflux was absent in 231 of the reimplanted ureters (97.5%) at the end of 5 years. No patient underwent reoperation for reflux. In 10 ureters (4.2%, 10 patients) obstruction developed postoperatively and 7 needed reoperation. All reoperations were performed on the left side. Of the obstructed kidneys new scars developed in 6 during the 5-year followup. Including these cases, the number of new renal scars was equal in the surgical and medical groups (20 each). The number of pyelonephritic episodes during followup was significantly less in the surgical group (without chemoprophylaxis) than in the medical group (on chemoprophylaxis). No kidneys were lost and no child became hypertensive. If voiding cystourethrography and excretory urography were normal 6 months postoperatively, the reflux had been permanently eradicated and postoperative obstruction could be ruled out. In this study the patients who underwent reimplantation had a 74% (112 of 151) chance of an uncomplicated postoperative course (no persisting reflux, obstruction, pyelonephritis or severe renal damage). PMID- 1433584 TI - Cessation of vesicoureteral reflux for 5 years in infants and children allocated to medical treatment. The International Reflux Study in Children. AB - A total of 401 children with severe vesicoureteral reflux (97 with grade III and 304 with grade IV) was entered into the European branch of the International Reflux Study in Children. Of these patients 37 with grade III and 43 with grade IV reflux were allocated to medical treatment as a sideline group because the reflux grade III or IV had improved to grade II or I, or it had disappeared during the preceding 2 to 6 months (median 4). Of the remaining 321 patients with persistent grade III or IV reflux 158 were randomly allocated to medical treatment of whom 3 switched to surgery. We report on 235 children treated medically (155 random medical and 80 sideline), of whom 88% had a complete 5-year followup with x-ray and/or isotope voiding cystourethrography at 6, 18, 30 and 54 months. Seven children dropped out of the study after a followup of 6 months or less, including 6 with persistent vesicoureteral reflux. Cessation of vesicoureteral reflux was observed significantly more often in children with unilateral (40 of 74, 54%) than with bilateral (18 of 154, 12%) reflux (p < 0.001). No significant difference between grades III and IV was noted. Vesicoureteral reflux ceased in 25 of 153 children (16%) from the random medical group and in 32 of 75 children (43%) in the sideline group. Of 194 children with vesicoureteral reflux detected for the first time at entry reflux resolved in 55 (28%). In only 2 of 34 children (6%) in whom vesicoureteral reflux was detected more than 1 year before entry did reflux resolve after 5 years. Among the children in whom vesicoureteral reflux either disappeared, diminished or remained unchanged the proportion with urinary tract infection recurrences was almost the same. PMID- 1433585 TI - Results of a randomized clinical trial of medical versus surgical management of infants and children with grades III and IV primary vesicoureteral reflux (United States). The International Reflux Study in Children. AB - A total of 132 infants and children with grades III and IV primary vesicoureteral reflux was entered into a prospective trial comparing medical to surgical management. Inclusion criteria were an age not exceeding 10 years and a glomerular filtration rate of at least 70 ml. per minute per 1.73 m.2. Children with significant urinary tract malformations and clinical signs/symptoms of dysfunctional voiding were not accepted into the trial. Medical therapy consisted of continuous low dose antibiotic prophylaxis until vesicoureteral reflux resolved. The type of surgical procedure used for the correction of reflux was left to the discretion of the surgeon. Outcome variables included the appearance or progression of renal lesions, rate of renal growth, recurrence rate of urinary tract infection or pyelonephritis, changes in total kidney glomerular filtration rate, development of hypertension and resolution rate of vesicoureteral reflux. Followup at 6, 18, 36 and 54 months after entry included, in addition to history and physical examination, voiding cystourethrography, excretory urography and a urine culture. Of the patients 68 were allocated to the medical group and 64 to the surgical group. They were stratified for age, sex and preexisting renal scarring. Of the patients 10% were boys, 47% were between 2 and 6 years old at entry, 93% had a history of pyelonephritis, 67% had either scarring or thinning of the parenchyma at entry, 87% had grade IV vesicoureteral reflux in at least 1 unit and 56% had bilateral reflux. There were no significant differences in the frequency distribution of entry characteristics between the patients allocated to either group. New renal scarring developed in 22% of medical and 31% of surgical patients (p < 0.4). Growth of kidneys with grade IV vesicoureteral reflux was slightly less than normal in the medical (-0.67 +/- 0.15 standard deviation) and surgical (-0.42 +/- 0.11 standard deviation) groups (p < 0.7). Pyelonephritis occurred in 15 medical patients versus 5 surgical patients (p < 0.05). There was no significant change in glomerular filtration rate within each treatment group and no difference in glomerular filtration rate between groups. No patient had hypertension during the followup period. The disappearance rate of vesicoureteral reflux in patients with grade IV reflux was approximately 8% per year. Of the medical patients 75% still had vesicoureteral reflux after 3 years of observation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1433586 TI - Surgical results: International Reflux Study in Children--United States branch. AB - A total of 87 patients in the United States underwent surgical correction of vesicoureteral reflux as part of the International Reflux Study in Children. Of the 66 patients randomized to surgical treatment 2 were transferred to the medical group before surgery was performed, while 23 patients originally assigned to receive medical management ultimately underwent surgery. Of the patients 17 (20%) were less than 1 year old, while the remaining children were evenly distributed by age in 2-year intervals up to age 9 years. Reimplantation was performed by the Cohen technique in 52% and by the Politano-Leadbetter technique in 28% of the patients. Bilateral reimplantation was done in 70 patients (80%). The results were satisfactory, with no obstructions. In 81% of the patients average followup was 3.9 years, although followup of less than 1 year in 19% was satisfactory to determine obstruction. Only 3% of the children were lost to followup. Postoperative reflux, which was noted in 5 patients, resolved in all but 1 ureter. These results reflect the experience of senior surgeons in pediatric urology. PMID- 1433587 TI - Commentary: management of children with severe vesicoureteral reflux. AB - The main findings of the IRSC after 5 years of observation are summarized. Of the 434 children entered 128 were from centers in America and 306 from Europe. They were randomly allocated and stratified to a medical or surgical regimen. Of the children 50% had scarred kidneys at entry evenly distributed between the groups. After 5 years of observation there was no difference in outcome between the 2 treatment groups in terms of renal size and growth, the development of new radiological renal scars or areas of parenchymal thinning, or of progression of established scarring. In Europe infection recurred in equal numbers of children but pyelonephritic symptoms were more common in the medical group. Nevertheless, new scars developed in 19 of 155 children treated medically and 20 of 151 children treated surgically, including 5 and 7, respectively, with previously normal kidneys. Factors influencing the choice of treatment include patient age, availability of expert surgical care and experienced medical supervision, parental choice and compliance. Followup studies indicate that renal scarring rather than persistence of reflux determines the prognosis and, therefore, emphasis should be placed on the prevention of scarring. PMID- 1433588 TI - Medical management of mild and moderate vesicoureteral reflux: followup studies of infants and young children. A preliminary report of the Southwest Pediatric Nephrology Study Group. AB - Mild and moderate vesicoureteral reflux is expected to resolve spontaneously in most children treated medically; however, maximum benefit or minimum risk of such therapy has not been defined. A prospective 5-year followup study of infants and children younger than 5 years at entry with primary vesicoureteral reflux (grades I to III/V) and radiographically normal kidneys after the first recognized urinary tract infection was initiated in 1984. A total of 113 patients was entered from 5 centers and 61% of the patients were less than 2 years old. Vesicoureteral reflux was unilateral in 65 cases (58%) and bilateral in 48 (42%). Of the 226 renal units reflux was grade IV in 4 (2%), III in 51 (22%), II in 81 (36%) and I in 25 (11%), and 65 (29%) had no vesicoureteral reflux. Data on 59 patients who have completed the protocol were analyzed for this report. Breakthrough urinary tract infection occurred in 20 patients. Of the 84 ureters with vesicoureteral reflux at diagnosis reflux resolved in 67%, and it was of lower grade in 22%, same grade in 8% and higher grade in 2%. Grade I vesicoureteral reflux resolved in 82%, grade II in 80% and grade III in 46% of the ureters. Resolution was better when vesicoureteral reflux was unilateral left (74%) than unilateral right (46%) or bilateral (60%). Renal scarring occurred, on average, in 10% of the kidneys without known vesicoureteral reflux or exposed only to nondilating (grades I and II) reflux and in 28% of those with dilating (grade III) reflux. Thirteen cases had breakthrough urinary tract infection but only after the scar was noted in 5. We conclude that under good medical management during 5 years of followup, even mild and moderate vesicoureteral reflux can be associated with renal injury. PMID- 1433589 TI - Followup of conservatively treated children with high and low grade vesicoureteral reflux: a prospective study. AB - A total of 202 children (mean age 31.5 +/- 23.3 months) with vesicoureteral reflux identified during the investigation that follows a urinary tract infection entered this prospective study dealing with the medical management of reflux. The diagnosis of vesicoureteral reflux was made significantly earlier in boys than in girls regardless of reflux grade (p < 0.001). At entry reflux nephropathy was present on a dimercaptosuccinic acid scan in 44% of 314 refluxing kidneys. There was no significant difference between boys and girls in the prevalence of reflux nephropathy. The renal lesions were more severe in boys independently of the grade of vesicoureteral reflux (p < 0.05). Breakthrough urinary tract infection was significantly more common in girls than in boys, regardless of vesicoureteral reflux grade (p < 0.05). Mean followup was 68.7 +/- 31.2 months. Patient age at the time of the first of 2 radionuclide cystograms without vesicoureteral reflux was considered the age of spontaneous resolution of reflux. Using life table estimations and analyzing data stratified to sex and grade of vesicoureteral reflux, we found that although reflux lasted longer in boys compared to girls, this difference was not statistically significant. During followup new scars developed in 7 patients related to breakthrough urinary tract infection. There was no significant difference between boys and girls in the development of new scars. To understand the natural history of vesicoureteral reflux children must be stratified by sex and grade of reflux. PMID- 1433590 TI - Commentary: the management of grades I and II (nondilating) vesicoureteral reflux. PMID- 1433591 TI - Historical clues to the complex of dysfunctional voiding, urinary tract infection and vesicoureteral reflux. The International Reflux Study in Children. AB - The prevalence of nonneuropathic bladder/sphincter dysfunction was assessed with a questionnaire in 310 of the 386 children enrolled in the European branch of the International Reflux Study in Children. Despite the exclusion criteria (neuropathic bladder, anatomical malformations other than vesicoureteral reflux and overt dysfunctional voiding or urge incontinence), the prevalence of bladder/sphincter dysfunction was as high as 18%. Four patterns of dysfunction emerged: urge syndrome, staccato voiding, fractionated and incomplete voiding, and voiding postponement. The questionnaire proved helpful in detecting low profile cases of bladder/sphincter dysfunction, as well as indicating the need for further urodynamic studies. A strong correlation was established between recurrences of urinary tract infections, as well as disappearance of vesicoureteral reflux (negative correlation) and nonneuropathic bladder/sphincter dysfunction. This finding implies that detection and treatment of bladder/sphincter dysfunction are essential in every child with the complex of recurrent urinary tract infection and vesicoureteral reflux. PMID- 1433592 TI - Relationship between dysfunctional voiding and reflux. AB - Bladder instability and the nonneurogenic neurogenic bladder are 2 urodynamically different dysfunctional voiding patterns. However, they share a common urodynamic mechanism in that they both produce functional urinary obstruction, which by changing the anatomy and function of the bladder, and ureterovesical junction produces and perpetuates vesicoureteral reflux. Urodynamic studies show that bladder decompensation with high end filling pressures, rather than high voiding pressures, is the mechanism for reflux and help to explain the seemingly paradoxical relationship among obstruction, reflux and high bladder pressures, namely that reflux does not usually occur when bladder pressures are high. This urodynamic analysis and review of the literature strongly support the belief that functional urinary tract obstruction caused by dysfunctional voiding can initiate and perpetuate vesicoureteral reflux, and provide an understanding of the mechanisms involved. PMID- 1433593 TI - Commentary: voiding dysfunction and reflux. PMID- 1433594 TI - Long-term followup of infants with gross vesicoureteral reflux. AB - The majority of children (1 year old or less) with gross vesicoureteral reflux already have renal damage at the time of presentation or reflux nephropathy develops during the first few years of life. We report the long-term followup of 31 patients (16 boys) presenting in infancy with gross vesicoureteral reflux (Rolleston classification) between 1952 and 1970. They had a total of 44 grossly refluxing ureters (13 bilateral, 18 unilateral) and presented between ages 1 day and 48 weeks (mean 15.3 weeks). Of the 31 infants 5 died within the first year of life, 4 were followed for up to 11 years before being lost to followup and 1 was killed in a motor vehicle accident after 19.5 years of followup. The remaining 21 patients have been followed for 16 to 37 years (mean 23.9 years); 4 have normal kidneys, and 13 have unilateral and 4 have bilateral reflux nephropathy. Of those patients with unilateral reflux nephropathy proteinuria, hypertension and renal failure developed in 1 born with a single kidney and he is now on hemodialysis, while 2 others have a diastolic blood pressure of 90 mm. Hg or greater. Of the 4 patients with bilateral reflux nephropathy 2 have proteinuria and renal insufficiency, with 1 progressing towards end stage renal failure. Infants who present with gross vesicoureteral reflux within the first year of life appear to do well if free of severe bilateral reflux nephropathy at presentation. Patients with reflux nephropathy should remain under regular nephrological supervision with particular attention given to proteinuria, renal function and blood pressure. PMID- 1433595 TI - Morphological characteristics of segmental renal scarring in vesicoureteral reflux. AB - We examined 25 complete and partial nephrectomy specimens from 21 patients with advanced reflux nephropathy, all of which showed severe renal atrophy and loss of parenchyma. All specimens that included nonatrophic or partially atrophic renal tissue contained small medullary scars that involved only portions of the medullary pyramids. These sublobar medullary scars, which appeared linear and were typically discrete, extended from the inner medulla to the cortex. They obliterated collecting ducts, vasa recta and recurrent loops. The cortical portions of the scars contained remnants of nephrons and variable infiltrates of chronic inflammatory cells with lymphoid follicles. Seven of the specimens also contained acute disruptive ductal lesions with histopathological features characteristic of intrarenal reflux. We believe that the linear scars are the result of single duct medullary disruptions, mediated perhaps through obstruction of the several thousand nephrons subtended by each papillary duct and perhaps through localized disruption of the renal microvasculature. These sublobar scars accumulate as scarring progresses to end stage renal atrophy. PMID- 1433596 TI - Long-term followup of renal morphology and function in children with recurrent pyelonephritis. AB - Renal morphology and function were evaluated in 161 children with recurrent pyelonephritis with or without vesicoureteral reflux and with or without scarred or small kidneys. The patients were followed for 1 to 21 years. Renal function was determined by glomerular filtration rate and effective renal plasma flow by clearances of inulin and paraaminohippuric acid. Of 105 children with normal kidneys originally small or scarred kidneys developed in 37, of whom 22 had grade III or greater vesicoureteral reflux, while small kidneys developed in 13 of 29 children with renal scarring originally. Of the 37 children with normal kidneys originally renal parenchymal scarring developed in 14 after the age of 4 to 5 years. Glomerular filtration rate was already < -2 standard deviations of that of controls in 51% of the patients at the first and in 53% at the last investigation of renal function. Of these patients with a glomerular filtration rate of < -2 standard deviations 69% had small or parenchymally reduced kidneys most of whom had the first pyelonephritis episode before age 3 years. Patients with small kidneys had a lower glomerular filtration rate than those with normal sized kidneys, whether scarred or not. The low glomerular filtration rate and its subsequent further reduction were related to kidney size and not to the presence or degree of vesicoureteral reflux. However, in individual patients the rate of functional deterioration could not be predicted from the radiological findings. Patients with bilateral small kidneys seemed to show the greatest decrease in glomerular filtration rate during followup as did those with grade III or greater reflux undergoing surgery bilaterally and those patients also had a lower glomerular filtration rate at the last investigation compared to patients not undergoing surgery. In conclusion, renal functional damage seems to occur early in the course of the disease and seems to be related to kidney size but there is a further slow progression with reduction in renal function which occurs, although this is difficult to predict from the radiological changes in individual patients. Therefore, patients with recurrent pyelonephritis should be followed regularly by glomerular filtration rate determination using an accurate method. PMID- 1433597 TI - Vesicoureteral reflux and pyelonephritis in the monkey: a review. AB - P-fimbriated Escherichia coli, which cause nonobstructive pyelonephritis, adhere to a specific urothelial glycolipid receptor. In either the presence or absence of reflux (in the area of turbulent urine flow) these bacteria ascend the ureter and cause a decrease in ureteral motility. Endotoxin causes peristalsis to cease, leading to ureteral dilatation and change in papillary shape, thus allowing intrarenal reflux and adherence of the bacteria to renal tubules. Bacterial infection of a refluxing ureter may cause reflux to persist. Once the bacteria reach the kidney rapid effects occur at the cellular level with activation of complement followed by granulocytic aggregation and capillary obstruction, causing renal ischemia and damage during reperfusion. In addition, during phagocytosis the respiratory burst occurs, releasing toxic oxygen molecules, which leads to renal tubular death, invasion of the interstitium, microabscess and renal scar formation, that is chronic pyelonephritis, which equates with reflux nephropathy. PMID- 1433598 TI - Commentary: progressive renal damage from infection with or without reflux. PMID- 1433599 TI - The long-term results of prospective sibling reflux screening. AB - A prospective study was begun more than 10 years ago to identify the incidence of vesicoureteral reflux in the siblings of patients with reflux. A total of 354 siblings of 275 index patients was screened with a voiding cystourethrogram for the presence of reflux. Of the siblings tested 119 (34%) were found to have reflux, including 75% who were asymptomatic. Reflux was present in a significant percentage of younger siblings. No correlation with index patient reflux grade, sex or established renal damage could be related to the likelihood of sibling reflux. A slightly higher rate of reflux was found in the female siblings of female index patients, which is a variation from the initial study. The incidence of renal damage was significantly reduced in the siblings with reflux compared to the index patients, which was also true in the youngest patients, who are believed to be the most susceptible to reflux-mediated renal damage. Sibling reflux screening can be justified due to a high percentage of siblings found to have reflux without symptoms and a significant decrease in renal damage compared to the index patients. Aggressive screening in young children (less than 5 years old) is still advisable, although this recommendation has been modified for older children. Additional information will be needed before the genetic transmission of reflux can be clarified. PMID- 1433600 TI - Fetal vesicoureteral reflux: outcome following conservative postnatal management. AB - Of 222 infants with a urinary tract abnormality detected antenatally 30 male and 9 female patients (64 renal units) were found to have primary vesicoureteral reflux. Grade of reflux was predominantly severe, with grade III or higher noted in 83% of the patients. Prenatal and postnatal ultrasound failed to detect any abnormality in 29 refluxing units (45%) discovered contralateral to the known abnormal system, although 19 had grade III or higher reflux. Of the 64 refluxing units 8 underwent primary ureteral reimplantation, 12 were lost to followup and 44 were managed conservatively for a mean of 3.3 years. Reflux ceased in 61% of the cases, improved in 14% and remained unchanged in 23%. In only 1 unit did the grade of reflux increase. Documented urinary tract infection occurred in 6 of the 39 reflux patients. Dimercaptosuccinic acid renography performed in 21 infection free patients demonstrated global reduction in renal parenchyma in 4 units, focal parenchymal defects in 3 and normal function in 14. Conservative postnatal management of fetal vesicoureteral reflux is justified. Global and focal parenchymal changes can occur in the kidneys of infants with reflux despite the absence of urinary tract infection. PMID- 1433601 TI - Commentary: importance of antenatal diagnosis of vesicoureteral reflux. AB - Although hydronephrosis detected by prenatal ultrasonography often is assumed to be secondary to obstructive uropathy, in approximately 10% of the cases renal pelvic dilatation results from primary vesicoureteral reflux. More than 80% of neonates with reflux are male and two-thirds have bilateral reflux. Approximately 80% have at least grade III reflux. At birth between a third and half may have reduced renal function on isotope renography, even in the absence of urinary infection. Approximately 20% of neonates with grade IV or V reflux followed nonoperatively experience spontaneous reflux resolution by age 2 years. However, in approximately 25% of boys followed nonoperatively urinary tract infections developed by age 2 years despite antimicrobial prophylaxis. Because the majority of these boys have been uncircumcised, circumcision seems advisable. Ureteral reimplantation should be reserved for those with breakthrough urinary tract infection, new renal scars or persistent high grade reflux. PMID- 1433602 TI - Commentary: vesicoureteral reflux--1992. PMID- 1433603 TI - Pediatric genitourinary rhabdomyosarcoma. PMID- 1433604 TI - Intrarenal access: 3-dimensional anatomical study. AB - In an attempt to determine the best route to puncture and access the kidney collecting system we studied 62, 3-dimensional polyester resin endocasts of the pelvicaliceal system together with the intrarenal vessels. A retrograde pyelogram was obtained, and the arterial and venous trees were injected with red and blue resins, respectively. When the resin was still in the gel state, the kidneys were positioned at 30 to 45 degrees and the collecting system was punctured under radioscopy. Since the resin is not opaque to x-ray the operator was not able to visualize the vessels while puncturing. After puncture, the needle was maintained in place, the contrast medium was removed and the pelvicaliceal system was filled with yellow resin. After the resin had set, the renal organic matter was corroded in acid and the endocast was obtained (with the needle in the original position). This type of preparation allowed us to examine the needle tract and the vessels damaged during the puncture. In the same kidney we punctured the superior pole, mid kidney and inferior pole. In some cases we also punctured the renal pelvis. We performed 104 punctures through an infundibulum, 39 through a fornix of a calix and 12 through the renal pelvis. Due to a high percentage of vascular lesions, intrarenal access through an infundibulum should be avoided. Also, renal pelvis puncture should be avoided. Regardless of the kidney region, puncture through a fornix of a calix was safe. PMID- 1433605 TI - Flow cytometric analysis of small renal tumors. AB - Flow cytometric deoxyribonucleic acid (DNA) content analysis was performed on 26 renal tumors 3.0 cm. or less in maximum diameter. We noted DNA aneuploid cell populations in 8 of 25 tumors (32%) evaluable for DNA ploidy status. DNA aneuploid cells comprised 7 to 59% of the cells in those tumors. In comparison, 12 of 25 tumors (48%) larger than 3.0 cm. had aneuploid cell populations. S phase cell populations were significantly increased in the small aneuploid tumors compared with the small diploid tumors (p < 0.001). We believe that these small tumors have the potential to behave aggressively and, therefore, they should be treated no differently than larger renal neoplasms. PMID- 1433606 TI - Interleukin-6 in renal cell carcinoma. AB - We studied interleukin-6 production in 4 human renal cell carcinoma cell lines and measured the serum level in 71 patients with renal cell carcinoma, thus, clarifying a relationship between interleukin-6 secretion and an occurrence of the paraneoplastic syndrome in the carcinoma. Interleukin-6 was produced by 3 cell lines and detected in 25% of the patients. The level of interleukin-6 did not directly correlate with tumor volume and the differentiation grade of the carcinoma. However, the positive rate increased with progression of the stage. The serum level affected the 5-year survival of patients without distant metastasis. When serum interleukin-6 was elevated patients had a significantly higher frequency of unexplained fever and an elevation of acute phase proteins. These results suggest that some renal cell carcinomas can produce interleukin-6 and this cytokine is responsible for several paraneoplastic syndromes in the carcinoma. PMID- 1433607 TI - The prognostic significance of vascular invasion in upper urinary tract transitional cell carcinoma. AB - The prognostic significance of vascular invasion was evaluated in a retrospective series of 30 patients with upper urinary tract cancer who underwent a potentially curative operation. Vascular invasion was found in 11 patients (36.7%). The incidence of vascular invasion was well correlated with tumor grade and stage. The incidence of metastases postoperatively was significantly higher in the patients with (72.7%) than without (21.1%) vascular invasion (p < 0.01). The survival rate of the patients with vascular invasion was significantly lower than in those without vascular invasion (p < 0.005). In multivariate Cox regression analysis the prognostic value of vascular invasion was independent of tumor stage and grade. These results indicate that vascular invasion should predict a more unfavorable outcome in patients with upper urinary tract cancer as an independent morphological indicator. PMID- 1433608 TI - In situ extracorporeal shock wave lithotripsy for obstructing ureteral stones with acute renal colic. AB - In situ (no instrumentation) extracorporeal shock wave lithotripsy (ESWL*) was used to treat 49 patients with obstructing ureteral stones causing acute renal colic. Ureteral obstruction was diagnosed on the delayed films of an excretory urogram and was classified as severe (dilatation above and no contrast medium seen below the stone) in 17 patients and partial (dilatation above and contrast medium seen below the stone) in 32. Upper third ureteral stones were present in 41 patients (obstruction severe in 15 and partial in 26) and lower third ureteral stones were present in 8 (obstruction severe in 2 and partial in 6). ESWL was performed within 14 days of the onset of the acute renal colic because of persistent pain with an unmodified Dornier HM3 lithotriptor in 17 patients and a Medstone STS device in 32. With single stones the stone-free rate at 3 months, the repeat ESWL rate and the secondary procedure (stone basketing) rate were 92%, 6% and 8%, respectively, with severe obstruction, and 78%, 6% and 6%, respectively, with partial obstruction. No urinary drainage procedures for sepsis were required after ESWL. Obstructing ureteral stones, which presented mainly in the upper third of the ureter, were successfully treated with in situ ESWL without the need for either bypassing the stone with a ureteral stent or for pushing the stone back into the kidney before treatment with ESWL. PMID- 1433609 TI - Clinical experience with flexible ureteropyeloscopy. AB - Flexible ureteroscopes and their accessory working instruments have undergone tremendous design advances since the earliest reports in the 1960s. These changes have allowed for the expansion of indications for flexible ureteroscopy with the emphasis now on therapeutic and not just diagnostic applications. This report covers 290 procedures done with actively deflectable, flexible ureteroscopes on 222 patients. Followup averaged 11.2 months in 228 patients, while the remaining 62 were followed by the original referral center. Included were 154 procedures for stones and 79 for tumors or filling defects. Of the procedures 149 were performed with the patient under local anesthesia with sedation, while 128 were done with use of general anesthesia. The procedure was done in only 22% of the cases for purely visual diagnosis without any interventional manipulation. More than 42% of the cases involved stone retrieval or lithotripsy, in which case the laser was most commonly used (56 cases). The total success rate was 95.5%, and the most common complications were colic or pain in 9% and fever in 6.9%. A stricture developed in 2 patients. A stent was left in more than 93% of the patients and the usual postoperative stay was less than 3 days. With the introduction of even more improved instruments, flexible ureteroscopy should continue to gain ground as an option for the management of upper urinary tract pathology. PMID- 1433610 TI - A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response. AB - From 1986 to 1990 the European Organization for Research and Treatment of Cancer- Genitourinary Group conducted a phase 2 trial of neoadjuvant chemotherapy in patients with stage T3-4N0-XM0 transitional cell carcinoma of the bladder. The objectives were to evaluate the clinical response in relation to the pathological response, and to measure the side effects of chemotherapy. Of 171 patients entered 136 were fully evaluable: 18% had clinical complete remissions, 36% had clinical partial remissions, 39% had no clinical remissions and 10% had unknown response. A selected subgroup of 76 patients underwent cystectomy after 2 or 4 courses of chemotherapy: 2 were not evaluable for pathological response because of preoperative radiotherapy after neoadjuvant chemotherapy, 16 had a pathological complete remission, 7 had a pathological partial remission and 51 had no pathological remission. Comparison of the clinical response or T category only after 2 courses of chemotherapy with the pathological response after 2 or 4 courses of chemotherapy showed that in a number of patients the disease status could be downstaged to pathological complete or partial remission by additional courses of chemotherapy. If the discrepancies between clinical and pathological responses, or between T and P categories, induced by further downstaging after additional chemotherapy were left out, it was shown that clinical complete and partial remissions were a heterogeneous group but nonresponders could be delineated with a 100% accuracy by clinical response evaluation and transurethral resection biopsy only. Furthermore it seems important to establish the number of chemotherapy courses to induce a maximal response of the primary tumor. PMID- 1433611 TI - Early experience with intraurethral collagen injections for urinary incontinence. AB - We report on 41 patients (10 men and 31 women) who underwent collagen injections for urethral incompetence. Mean followup was 6 months (range 3 to 11 months) in men cured or improved, 8.4 months (range 3 to 15 months) in women who were cured and 4.5 months (range 2 to 10 months) in women who were improved. In women the procedure was usually performed through a periurethral approach while they were under local anesthesia and in men it was performed transurethrally while under either general or local anesthesia. Of the 31 women 28 (90.3%) were cured (15) or improved (13). Mean maximum Valsalva pressure increased from 31 cm. water before injection to 85 cm. water at 6 months after injection in women who were cured or improved. The mean amount of collagen used in the female group was 12.7 cc (range 2.5 to 47.5) and the mean number of treatments was 2 (range 1 to 7). Of the men 7 (70%) had successful results (2 cured and 5 improved). In contrast to the women, they required a mean of 51.8 cc (range 7.5 to 82.5) of collagen and a mean of 6 treatments (range 3 to 12). Of 5 patients with bladder instability 4 did not improve. One patient suffered acute bacterial prostatitis and 2 patients had post injection urinary retention. All women with little or no bladder neck hypermobility (types 1 and 3) were either cured or improved. We conclude that intraurethral collagen injection is safe and simple to perform. The results achieved in women are acceptable. In men, while collagen does provide improvement, the cost-to-benefit ratio and effectiveness are less than those in women. Instability may obviate a good outcome. PMID- 1433612 TI - The need for antibiotic prophylaxis of patients with penile implants during invasive dental procedures: a national survey of urologists. AB - A national survey of urologists was conducted regarding the need for prophylactic antibiotic coverage for patients with penile implants when undergoing invasive dental treatment. A total of 1,756 questionnaires was sent to urologists in the United States and 297 responses were received, for a participation rate of 17%. The low response rate might be partly related to a low level of concern by urologists due to the lack of reported cases of penile implant infections following invasive dental procedures and the lack of the literature calling attention to this possible association. This is supported by the fact that none of the responding urologists had noted any case of infection of the prosthesis following dental treatment. The majority of urologists who responded did not recommend antibiotic prophylaxis for penile implant patients undergoing invasive dental treatment. The majority of urologists who recommended prophylaxis selected a cephalosporin. None of the responding urologists indicated that they were aware of infection developing in any penile implant patients following invasive dental treatment. The dentist is advised to consult with the urologist of patients with penile implants on an individual basis to determine the need for antibiotic prophylaxis. PMID- 1433613 TI - Risk factors for male partner antisperm antibodies. AB - The role of antisperm antibodies in human infertility remains controversial. Indications for antisperm antibody testing of male partners of infertile marriages have been based upon anecdotal reports and studies using outdated assays. In an effort to define the indications for antisperm antibody testing of the male partner, the immunobead assay for antisperm antibodies was performed upon 100 consecutive men referred for evaluation of male factor infertility. The prevalence of antisperm antibodies in this patient population was 18% and only 9% when patients with a history of vasectomy were excluded. Of all the factors analyzed, only a history of vasectomy and sperm agglutination on semen analysis were predictive of antisperm antibody status (p < 0.001). Use of the aforementioned parameters as an indication for antisperm antibody testing would have resulted in a sensitivity of 94%, specificity 73% and negative predictive value 98% in this patient population. The only way to identify all patients with significant levels of antisperm antibody activity (sensitivity 100%) would have been to test every patient. PMID- 1433614 TI - Microsurgical inguinal varicocelectomy with delivery of the testis: an artery and lymphatic sparing technique. AB - Conventional techniques of varicocele repair are associated with substantial risks of hydrocele formation, ligation of the testicular artery, and varicocele recurrence. We describe a microsurgical technique of varicocelectomy that significantly lowers the incidence of these complications. The testicle is delivered through a 2 to 3 cm. inguinal incision, and all external spermatic and gubernacular veins are ligated. The testis is returned to the scrotum and the spermatic cord is dissected under the operating microscope. The testicular artery and lymphatics are identified and preserved. All internal spermatic veins are doubly ligated with small hemoclips or 4-zero silk and divided. The vas deferens and its vessels are preserved. Initially, we performed 33 conventional inguinal varicocelectomies in 24 men without delivery of the testis or use of a microscope. Postoperatively, 3 unilateral hydroceles (9%) and 3 unilateral recurrences (9%) were detected. For the next 12 cases 2.5x loupes were used resulting in no hydroceles but another recurrence (8%). We then performed 640 varicocelectomies in 429 men using the microsurgical technique with delivery of the testis. Among 382 men available for followup examination from 6 months to 7 years postoperatively no hydroceles and no cases of testicular atrophy were found. A total of 4 unilateral recurrent varicoceles (0.6%) was identified. The differences between the techniques in the incidence of hydrocele formation and varicocele recurrence are highly significant (p < 0.001). No wound infections occurred in any men. Four scrotal hematomas (0.6%), 1 of which required surgical drainage, occurred in the group with microsurgical ligation and delivery of the testis compared to none with the conventional technique. Preoperative and postoperative semen analyses (mean 3.57 analyses per patient) were obtained on 271 men. The changes in sperm count x 10(6) cc (36.9 to 46.8, p < 0.001), per cent motility (39.6 to 45.7%, p < 0.001) and per cent normal forms (48.4 to 52.10%, p < 0.001) were highly significant. The pregnancy rate was 152 of 357 couples (43%) followed for a minimum of 6 months postoperatively. Delivery of the testis through a small inguinal incision provides direct visual access to all possible avenues of testicular venous drainage. The operating microscope allows identification of the testicular artery, lymphatics and small venous channels. This minimally invasive, outpatient technique results in a significant decrease in the incidence of hydrocele formation, testicular artery injury and varicocele recurrence. PMID- 1433615 TI - Laparoscopic unroofing of a renal cyst. AB - Excision of a renal cyst via the flank approach results in a painful postoperative recovery requiring several days of hospitalization. We used laparoscopy in a selected patient to unroof a large complex renal cyst. The technique could optimally be used for simple cysts. The procedure was minimally traumatic, morbidity was negligible and the patient was discharged from the hospital the morning after the operation. After a 6-month followup, we believe that this laparoscopic technique is a significant advance in urological surgical management and may be better indicated for symptomatic, recurrent, simple renal cysts. PMID- 1433616 TI - Laparoscopic removal of bladder diverticulum. AB - A large symptomatic bladder diverticulum in a 72-year-old man was removed through laparoscopic dissection. The surgical technique of laparoscopic diverticulectomy is described. Laparoscopic diverticulectomy can be done with minimal morbidity and has distinct advantages over other forms of treatment of bladder diverticula. PMID- 1433617 TI - Urodynamic effects of intravesical instillation of terodiline in healthy volunteers and in patients with detrusor hyperactivity. AB - The effects of intravesical instillation of terodiline on urodynamic parameters were investigated in 8 healthy volunteers (10(-4) M.) and in 34 patients with detrusor hyperactivity (10(-5) M.) of neurogenic (22) or nonneurogenic (12) origin. The volunteers were investigated with conventional medium-fill cystometry, while in the patients a modified cystometric technique with slow intermittent filling was used. The reproducibility of the procedure was verified in 17 patients. Instillation of terodiline had no effect on the normal bladders nor were any improvements found in the nonneurogenic patients. In 12 patients in the neurogenic group treated with terodiline instillation the bladder capacity increased significantly (p < 0.05) from 289 +/- 32 to 413 +/- 55 ml. Within this group 5 patients were responders. It is suggested that pathophysiological changes may explain the difference between the neurogenic and nonneurogenic groups, and that the number of responders within the neurogenic group may be increased by an optimal drug preparation and increased dosage. Intravesical administration of terodiline may offer an alternative treatment in selected patients with detrusor hyperreflexia. PMID- 1433618 TI - Function of the conus medullaris and cauda equina in the early period following spinal cord injury and the relationship to recovery of detrusor function. AB - A total of 26 patients with an early suprasacral spinal cord injury underwent comprehensive neurourological evaluation to determine if there was any correlation between the return of detrusor function and neural function of the sacral cord. In addition, the incidence of a subclinical sacral neural dysfunction early after spinal cord injury was assessed. Lumbosacral evoked potentials to tibial nerve stimulation were used to assess the sensory root and cord gray matter of the L5 to S2 segments, while urodynamic evaluation was performed to assess detrusor function. Of those patients with normal lumbosacral evoked potentials 82% recovered detrusor contractility as opposed to 66% with abnormal evoked potentials. Four patients (23.5%) had persistent detrusor areflexia when studied 9 to 20 months following the acute injury. The potential problems attempting to correlate the neurophysiological and urodynamic studies are multiple and are extensively discussed. Despite these potential problems the return of detrusor function correlated well with associated normal lumbosacral evoked potentials suggesting that this test can be used in the early phase following spinal cord injury to predict return of bladder function, since it is independent of the level of spinal cord excitability. Of the patients studied 38% had coexistence of an occult lumbosacral dysfunction. This rate is higher than that found in the chronic stabilized spinal cord injury population (20.5%), since the cases in our study may represent a more severe lesion. PMID- 1433619 TI - Effects of acute bolus and chronic continuous intrathecal baclofen on genitourinary dysfunction due to spinal cord pathology. AB - A prospective, blinded study was done to examine the effects of acute bolus and chronic continuous intrathecal baclofen on genitourinary function in 10 patients with severe spasticity due to spinal cord pathology. Genitourinary function was assessed by symptom questionnaires and urodynamic studies performed after a bolus dose of baclofen and 6 to 12 months after continuous intrathecal baclofen. Results were compared to placebo for acute bolus testing or to pre-continuous intrathecal baclofen values. In all patients with irritative voiding and urge incontinence uninhibited bladder contractions were eliminated. Of 3 patients with an indwelling urethral catheter for incontinence due to detrusor hyperreflexia 1 was converted to intermittent self-catheterization. Whereas bladder capacity, compliance, sensation and voiding pressures were not different after continuous intrathecal baclofen, when a mean of all patients was compiled, a 72% increase in capacity and 16% improvement in compliance were observed in subjects without cervical spinal cord pathology. Detrusor-sphincter dyssynergia was abolished in 40% of the patients. Continuous intrathecal baclofen may represent a novel approach to the management of patients with a neurogenic bladder who have decreased bladder compliance and detrusor hyperreflexia not controlled by oral medications. PMID- 1433620 TI - The prognostic value of bladder contractility in transurethral resection of the prostate. AB - The contractility of the bladder as quantified by a parameter of approximated power per bladder surface area based on the Hill equation (Wmax) was calculated for 29 patients before and 3 months after transurethral resection of the prostate. There was no significant change in this parameter as a result of the operation. Patients who still had a significant amount of residual urine postoperatively had decreased contractility before and after surgery so that the postoperative condition could have been predicted preoperatively. In many patients a fading contraction was observed, that is detrusor contractility decreased during voiding, which gave rise to a significantly increased volume of residual urine. In most patients this pattern was restored to normal after relief of the obstruction, indicating that it was not related to structural changes in the detrusor muscle. A preoperative fading contraction had no predictive value towards the outcome of the operation. PMID- 1433621 TI - Continence after radical cystoprostatectomy and total bladder replacement: a urodynamic analysis. AB - Urodynamic evaluation was performed in 10 patients after radical cystoprostatectomy and continent urethral diversion with detubularized ileum and in 13 patients continent after radical prostatectomy. In both groups surgical techniques were modified to optimize preservation of the periurethral tissue at the prostatic apex. For the ileal neobladder group 9 patients (90%) were completely continent and 1 (10%) noticed moderate nocturnal incontinence. The urethral sphincteric mechanism was well preserved in these patients, with no significant difference between the 2 groups in mean functional urethral length (3.8 +/- 0.6 versus 3.6 +/- 0.8 cm., p = 0.55) or maximal urethral closure pressure (87 +/- 34 versus 74 +/- 20 cm. water, p = 0.26). Tubularization of the bladder or neobladder above the level of the external sphincter was noted in both groups. Continence after radical cystoprostatectomy with continent urethral diversion and after radical prostatectomy is dependent upon an intact urethral sphincteric mechanism as well as a compliant, low pressure reservoir, either bladder or a bladder substitute. Urinary incontinence after total bladder replacement with detubularized ileum can be minimized by preserving as much of the distal urethral sphincter as possible. This can be done by careful dissection of the prostatic apex, performed under direct vision, with an understanding of the anatomy of the urethral sphincter and its innervation. PMID- 1433622 TI - False diagnosis of renal transplant urinary leakage on scintigraphy with mercaptoacetyltriglycine. AB - 99mTechnetium-mercaptoacetyltriglycine (99mTc-MAG-3) has rapidly become the best isotope for transplant renal scintigraphy because of the excellent anatomical resolution. Because 99mTc-MAG-3 is also sequestered by the liver and excreted into the biliary system, images of the gallbladder and intestinal tract will appear in normal 99mTc-MAG-3 scans, especially on delayed scintigraphs. We describe the clinical interpretation of normal bowel images as urinary extravasation in a renal transplant recipient with a sudden decrease in renal function. PMID- 1433623 TI - Retroperitoneal neurogenous choristoma. AB - A 6-year-old girl with urinary complaints underwent ultrasonography, which revealed a retroperitoneal cystic mass adjacent to the left kidney. Computerized tomography did not demonstrate whether the mass was an adrenal cyst or a duplicated upper pole segment. Exploration revealed a neurogenous choristoma, which is a collection of histologically normal tissue that is ectopically situated. We believe that this is the first report of this rare entity occurring in the retroperitoneum. PMID- 1433624 TI - The transmission of vesicoureteral reflux from parent to child. AB - Vesicoureteral reflux is now recognized to be hereditary and familial. The incidence of reflux in siblings has proved to be significant but less is known about the incidence of reflux in the offspring of known reflux patients. In an ongoing prospective series of reflux screening we identified 23 patients of childbearing age with a known history of reflux and screened their 36 offspring with an awake voiding cystourethrogram. Of these 36 offspring 24 (66%) exhibited vesicoureteral reflux. The literature was also reviewed to determine the incidence of parent/child reflux from reported cases. This review revealed a 65% rate of reflux in the offspring of known patients. Our preliminary results coupled with those in the literature signify a need to screen the offspring of known reflux patients and suggest a rethinking of the genetic transmission for this trait. While vesicoureteral reflux could still be a multifactorial genetic trait with a major gene, consideration must also be given to an autosomal dominant inheritance pattern. PMID- 1433625 TI - Median raphe cysts of the genitalia. AB - We report 2 recent cases of midline cysts of the genitoperineal raphe in children, and discuss the embryogenesis, diagnosis and management. Congenital anomalies of an unclear etiology, median raphe cysts are probably more common than has been reported in the literature. Medical attention is usually sought for secondary infections or pain with intercourse. Awareness and prompt identification of these entities by urologists are essential for proper management when differentiation from other more formidable lesions, including urethral diverticula, becomes important. Simple surgical excision is effective in most cases. PMID- 1433626 TI - Urinary tract infections in children with posterior urethral valves after kidney transplantation. AB - The records of 14 boys with posterior urethral valves who had renal failure and subsequently underwent renal transplantation were reviewed to determine the postoperative incidence of urinary tract infection relative to that of 29 male transplant children without valves, who served as controls. There were no significant differences between the posterior urethral valve patients and controls with regard to age, donor source, immunosuppression, followup after transplantation or mean calculated creatinine clearance. Vesicoureteral reflux was found in 1 child with posterior urethral valves and 3 of the children in the control group (p not significant). A total of 15 urinary tract infections occurred in 5 children (36%) with posterior urethral valves, for a rate of 1 per 30 patient-months of followup, and 6 urinary tract infections occurred in 2 controls (7%), for a rate of 1 per 216 patient-months of followup (p < 0.05). However, only 1 of 26 controls (4%) without vesicoureteral reflux had urinary tract infection, for a rate 1 per 1,144 patient-months (p < 0.01). Conversely, the rate of urinary tract infections in controls with vesicoureteral reflux was similar to that of children with posterior urethral valves. Of the 5 children with posterior urethral valves 4 had the initial urinary tract infection within 2 months of transplantation and 10 of 15 episodes occurred within the first 4 months. Antimicrobial prophylaxis did not appear to decrease the rate of infection in children with posterior urethral valves. A history of posterior urethral valves increases the frequency of urinary tract infection after renal transplantation but the usefulness of antimicrobial prophylaxis and the relationship to long-term graft function remain to be determined. Urinary tract infection rarely develops in other transplanted boys without vesicoureteral reflux. PMID- 1433627 TI - Hydronephrosis secondary to congenital pelvic arteriovenous malformation: a case report. AB - We report on a 26-year-old woman with a pelvic mass that caused ureteral obstruction and a hydronephrotic kidney. Diagnosis was congenital pelvic arteriovenous malformation and surgery was successful. The patient underwent staged preoperative intra-arterial embolization to decrease operative morbidity and facilitate complete removal. PMID- 1433628 TI - Diagnostic and therapeutic problems in multicentric renal angiomyolipoma. AB - Multicentric renal angiomyolipoma is a rare form of benign tumor. However, its effective incidence as evaluated in autopsy studies may be as high as 8%. There are 2 main types of renal angiomyolipoma, that is isolated forms and those associated with other diseases, such as phakomatosis, polycystic kidneys and fibromuscular dysplasia. The tumor may also display malignant behavior with local invasiveness and regional lymph node involvement. However, the clinical course is benign and multicentricity is important for prognosis. Histopathological diagnosis often is difficult. Immunohistochemical analysis of surgical specimens using a panel of monoclonal antibodies, including HMB-45 and actin, enabled us to make a definitive diagnosis in 3 cases of multicentric renal angiomyolipoma. PMID- 1433629 TI - Bilateral renal angiomyolipoma associated with bilateral renal vein and inferior vena caval thrombi. AB - We report a case of bilateral renal angiomyolipoma with thrombosis of the bilateral renal veins and inferior vena cava. Right partial nephrectomy and total thrombectomy were performed. To our knowledge only 5 cases of invasion of the inferior vena cava have been described. We report a case in which the renal veins were involved bilaterally. Treatment modalities are discussed. PMID- 1433630 TI - Unilateral ureteral obstruction secondary to rupture of liver echinococcal cyst. AB - We report a case of ureteral obstruction by reactive retroperitoneal fibrosis secondary to rupture of a liver echinococcal cyst after minimal blunt flank trauma. The patient presented initially with a cyst-cutaneous fistula and was treated with mebendazole, since surgery was refused. Unilateral ureteral obstruction due to reactive dense retroperitoneal fibrosis developed 2 years later, which presumably was initiated by intense inflammatory reaction to the cyst content. Diagnosis was established by excretory urography, ultrasonography and computerized tomography, and was histologically confirmed. Hydronephrosis and hydroureter resolved following ureterolysis. This complication is anticipated to be encountered more frequently with the use of the new potent anthelmintic agents, which may successfully prevent daughter cyst formation but fail to abolish reactive retroperitonitis. PMID- 1433631 TI - Delayed spontaneous rupture of an ileocolonic neobladder. AB - A case of delayed spontaneous rupture of an ileocolonic neobladder and subsequent peritonitis 4 years after the initial operation is reported. Many of the features of this case are similar to those noted in recent reports of spontaneous rupture of an augmented bladder and it is postulated that the etiology is the same. PMID- 1433632 TI - Complications of intravesical bacillus Calmette-Guerin: a case report. AB - Bacillus Calmette-Guerin (BCG) is the most effective agent currently available to treat superficial bladder cancer. However, this form of therapy is not without potential serious or fatal complications. In addition to the potentially toxic systemic side effects attributed to hematogenous absorption of the bacillus, direct upper tract seeding may occur in patients with vesicoureteral reflux. We report on a patient treated with intravesical BCG for bladder cancer in whom unilateral necrotizing granulomatous pyelonephritis developed. Although severe, this complication is rare and we conclude that reflux is not a contraindication for intravesical BCG therapy. PMID- 1433633 TI - Clinical evidence of systemic persistence of bacillus Calmette-Guerin: long-term pulmonary bacillus Calmette-Guerin infection after intravesical therapy for bladder cancer and subsequent cystectomy. AB - A patient with urothelial bladder carcinoma is reported who suffered from culture proved pulmonary bacillus Calmette-Guerin (BCG) infection 14 months after a single course of intravesical BCG and 11 months after subsequent radical cystectomy for progressive cancer. This unusual case raises the question of the ultimate fate of intravesically instilled BCG and the possible persistence of these mycobacteria in remote organs. Systemic spread and dormant survival at least in some cases are suggested, and therapeutic and diagnostic consequences are discussed. PMID- 1433634 TI - Invasive bladder cancer following 125iodine implants. AB - We present 2 cases of invasive transitional cell carcinoma of the bladder following implantation of 125iodine seeds for the treatment of localized adenocarcinoma of the prostate. These tumors, which occurred approximately 6 years after radiotherapy, were located in the trigone and prostatic urethra within the previous radiation treatment field. The development of high grade transitional cell carcinoma in these patients may be due to the tumorigenic effects of 125iodine radiation. PMID- 1433635 TI - Significant obliteration of the urethral lumen after Wallstent implantation. AB - The permanently implanted self-expandable urethral stent (Wallstent) has found increased use in patients with recurrent urethral strictures because of its simple implantation technique. To date there have been no reports of serious complications. At 6 weeks after stent implantation our patient had complete luminal obstruction. This complication demonstrates the need for short-term controls after implantation of a urethral stent. PMID- 1433636 TI - Malacoplakia of the urethra: a case of unique localization with followup. AB - A case of malacoplakia of the urethral meatus, without any association of vesical involvement, or any other synchronous or metachronous localization is presented. To our knowledge this is the fourth case in the literature at this site. The patient was free of disease 9 years after excision. PMID- 1433637 TI - Prosthetic penile infection: "rescue procedure" with rifamycin. AB - Penile prosthetic implantation is a successful procedure for the management of male erectile impotence. However, infection remains the most serious complication requiring removal of the device. Later reinsertion can be difficult due to fibrosis and a shortened penis. We present 3 cases of penile infection with Staphylococcus epidermidis in which a new penile prosthesis was placed after 72 hours of continuous irrigation of the corpora cavernosa with rifamycin. The procedure requires judicious selection of patients and a stable clinical status. PMID- 1433638 TI - Laparoscopic retroperitoneal lymph node dissection in a patient with stage 1 testicular carcinoma. AB - Minimally invasive laparoscopic surgical techniques are being increasingly applied to the treatment of urological diseases. We report a case of a laparoscopically performed modified bilateral retroperitoneal lymph node dissection for clinical stage 1 testicular cancer. The laparoscopic surgical approach to the retroperitoneal nodes is a technically feasible procedure that can remove lymph node tissue from all primary landing sites for testicular cancer metastases with potentially decreased morbidity. PMID- 1433639 TI - Endoscopic hydrocele ablation. AB - A new technique for the treatment of hydroceles by percutaneous drainage and endoscopic ablation under direct vision is described. The possible benefits and drawbacks of this treatment modality for symptomatic hydroceles are discussed. PMID- 1433640 TI - Near fatal liver dysfunction secondary to administration of flutamide for prostate cancer. AB - A 66-year-old man with metastatic prostate cancer was treated with bilateral orchiectomy and 750 mg. flutamide per day. Near fatal liver dysfunction developed 10 weeks later. Flutamide was discontinued and 8 weeks later liver enzymes had returned to normal. PMID- 1433641 TI - Urodynamics in the early stages of spinal cord compression from prostate adenocarcinoma. AB - Acute urinary retention developed in 2 patients with a history of prostate cancer. Urodynamic evaluation revealed autonomic dysfunction, which contrasted with a prior urodynamic study, indicating a possible spinal lesion. Radiographic evaluation led to early diagnosis and treatment of spinal cord compression from metastatic prostate adenocarcinoma. We discuss the diagnostic role of urodynamics in such cases. PMID- 1433642 TI - Successful use of fluconazole for treatment of urinary tract fungal infections. AB - Two cases are reported that demonstrate significant activity of the new antifungal agent, fluconazole, in treating urinary tract fungal infections. One patient was severely immunocompromised with the underlying complication of renal failure and the other presented with a much simpler case of candidal cystitis that responded quickly despite unfavorable in vitro susceptibility testing. PMID- 1433643 TI - Re: Pharmacological erection program using prostaglandin E1. PMID- 1433644 TI - Re: Pharmacological erection program using prostaglandin E1. PMID- 1433645 TI - Re: Correlation of testicular color Doppler ultrasonography, physical examination and venography in the detection of left varicoceles in men with infertility. PMID- 1433646 TI - Re: Coagulase-negative Staphylococcus in chronic prostatitis. PMID- 1433647 TI - Reduction in the length of the intravesical ureter associated with pyelonephritis in the adult pig. AB - The ureterovesical junction of pigs with cystitis and pyelonephritis was examined. There was significant shortening of the intravesical portion of the ureter in sows with pyelonephritis. In cases associated with acute pyelonephritis the ureteric orifice was found to be significantly wider than that found in the normal population. The ratio of the intravesical length to the ureteric orifice diameter was also significantly reduced. It is postulated that these changes to the ureterovesical junction originate or are caused by the disease processes in the bladder and may allow vesicoureteric reflux to occur, leading to ascending pyelonephritis. PMID- 1433648 TI - Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome. AB - A rodent model of hereditary cancer in which a single gene mutation predisposes rats to bilateral multicentric renal cell carcinoma (RCC) is described. This rat hereditary cancer syndrome shares certain similarities with von Hippel-Lindau disease (VHLD). In addition to the early development of renal epithelial tumors with morphologic similarity to human RCC, rats which bear the RCC gene are predisposed to the development of secondary primary cancers later in life. Splenic vascular proliferative lesions, including hemangiosarcoma, were seen in 23% of 14-month-old rats of both sexes that had renal tumors. At fourteen months of age, 62% of female rats with renal cell tumors had sarcomas of the lower reproductive tract of probable smooth muscle origin. Non-carrier siblings of affected animals did not have renal, reproductive, or splenic neoplasia. The finding of a specific constellation of familial neoplasms, including multicentric bilateral renal cell carcinoma, in this autosomal dominant disorder of rats suggests that this syndrome is analogous to human VHLD. In addition to its usefulness for studies of the biochemical and molecular mechanisms of renal carcinogenesis, this animal model will provide a unique tool to investigate how cancer susceptibility genes interact with environmental risk factors such as chemical carcinogens. PMID- 1433649 TI - Effect of tetrodotoxin on the phasic and tonic responses of isolated rabbit urinary bladder smooth muscle to field stimulation. AB - The response of the rabbit urinary bladder to field stimulation (80 volts, 2-32 Hz, 1 msec duration) is biphasic, consisting of an initial phasic contraction mediated by cholinergic and purinergic neurotransmitters, followed by a prolonged tonic contraction which is solely cholinergic. Obstructive hypertrophy of the bladder induces a variety of contractile alterations including a significantly greater reduction in the tonic component of the contractile response as compared to the phasic component. This results in a severe dysfunction in the ability of the bladder to empty. One possibility is that the inability of the bladder to maintain tension and empty efficiently may be related to a degeneration of nerves innervating the bladder smooth muscle. In addition to the well documented neuropathy, the bladder undergoes hypertrophy +/- hyperplasia of both smooth muscle and interstitial cellular elements, alterations in the metabolism of substrates, alterations in the synthesis of structural and smooth muscle proteins, and alterations in the deposition of collagen. The purpose of this study was to 1) to create a specific neuropathy in the absence of the additional structural, smooth muscle, and metabolic changes that are induced by partial outlet obstruction; and 2) determine if the contractile dysfunctions induced by the neuropathy have properties similar to the contractile dysfunctions induced by outlet obstruction. In the present study, a progressive "smooth muscle neuropathy" was induced in isolated strips of male rabbit urinary bladder smooth muscle by incubating isolated strips of urinary bladder body in the presence of increasing concentrations of tetrodotoxin (15-1500 nM). In these studies, we determined the effect of increasing concentrations of tetrodotoxin (TTX) on the response to field stimulation utilizing 2 Hz and 32 Hz, at 80 V and 1 ms duration. The effects of TTX on maximum rate of contraction, peak contraction and tonic contraction were monitored. In addition, the effects of atropine (cholinergic muscarinic blockage) and ATP-desensitization (purinergic inhibition) on the effects of TTX were also determined. The results can be summarized as follows: 1) Both atropine and ATP desensitization individually inhibited significantly the peak response to field stimulation. 2) Atropine abolished the tonic response. 3) TTX inhibited the tonic contraction at significantly lower concentrations than it inhibited peak contraction. Thus, at low concentrations of TTX, a condition similar to that seen in obstructive hypertrophy was created. 4) The ED50 in the presence of atropine was significantly greater than the ED50 following ATP desensitization. This may indicate that there are separate synaptic elements for cholinergic and purinergic transmission.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1433650 TI - The fate of buried vaginal epithelium. AB - A new technique in the treatment of stress urinary incontinence utilizes a sling fashioned from a rectangular island of buried vaginal epithelium. We developed a model to study the natural history of vaginal wall covered by an epithelial flap in 12 rabbits sacrificed at intervals to 26 weeks. Histopathologic examination demonstrated an immediate acute inflammatory reaction. This early response was followed by formation of an epithelial lining of the potential space overlying the buried vaginal tissue. Acute inflammatory cells continued to enter this lumen until week 20, when granulomas were first detected. Histopathologic examination at twenty-six weeks showed stratified squamous epithelium lining the lumen. No deleterious inflammatory sequelae were detected, and no dysplastic or malignant changes were identified. These results suggest that buried vaginal epithelium is a safe (short term) tissue alternative for sling creation. PMID- 1433651 TI - Experimental autoimmune cystitis: a potential murine model for ulcerative interstitial cystitis. AB - Interstitial cystitis is an inflammatory disease of unknown etiology. To facilitate the study of the pathophysiology of interstitial cystitis, an animal model that correlates with the clinical features of interstitial cystitis and expresses histologic features consistent with those observed in interstitial cystitis patients was developed. Various strains of mice were immunized with a syngeneic bladder homogenate to determine their susceptibility to the induction of autoimmune cystitis. Of 3 mouse strains tested, only the Balb/cAN mice reproducibly developed the clinical correlates and histological features consistent with those observed in interstitial cystitis. In a blinded pathologic review, autoreactive Balb/cAN bladders were correctly distinguished from chronic bacterial cystitis, sham treated bladders and normal control bladders. Edema, fibrosis, perivascular lymphocytic infiltrations and detrusor mast cell accumulation were apparent in 75% of the Balb/cAN mice 2 weeks after immunization and 100% at 4 weeks. These histologic features plateaued and remained stable for at least 6 months. Grossly, the immunized mouse bladders were fibrotic and contracted with a significantly (p < .05) decreased fluid capacity. On hydrodistension, increased vascular prominence and petechial hemorrhage (glomerulations) were evident. Instillation of 14C-urea demonstrated increased permeability in immunized bladders compared with controls. A cellular autoimmune basis for the cystitis is supported by adoptive transfer studies. Spleen cells from experimental mice but not controls transferred the histological features of the disease to naive mice. These studies outline the development of a new experimental autoimmune cystitis model that expresses features similar to those frequently observed in human interstitial cystitis, and may provide a model for the study of the inflammatory process associated with interstitial cystitis. Furthermore, these data suggest a possible role for cellular immune components in interstitial cystitis. PMID- 1433652 TI - Venous ulcers, the vascular surgeon, and the Medicare budget. PMID- 1433653 TI - The role of air plethysmography in monitoring results of venous surgery. AB - The development of an objective, noninvasive method to assess the hemodynamic effects of venous surgery has long been awaited. Previous methods used to evaluate the results of surgery for varicose veins and venous stasis ulceration have been limited in their quantitative assessment. Now, by use of air plethysmography (APG), we can accurately quantify the effectiveness of corrective venous surgery. Twenty-five extremities that had evidence of venous insufficiency were examined with use of APG before and after venous surgical procedures. Surgery was directed at specific sites of venous incompetence as defined by physical examination and high-resolution duplex imaging. Twenty-one extremities underwent ligation and stripping of the greater saphenous vein. In these patients, APG showed an improvement in venous reflux as demonstrated by a decrease in the venous filling index from 6.6 +/- 0.7 ml/sec to 1.8 +/- 0.3 ml/sec (p = 0.0001) and venous volume from 177.1 +/- 14.5 ml to 139.2 +/- 8.9 ml (p = 0.0008). In addition, these patients showed a mild improvement in calf muscle pump function as noted by an improvement in ejection fraction from 45.8 +/ 2.0% to 50.8% +/- 2.5% (p = 0.07). The residual volume fraction decreased from 45.0% +/- 3.4% to 42.0% +/- 3.7%, a difference that was not statistically significant (p = 0.4). Four extremities with grade III chronic venous insufficiency underwent popliteal vein valve transplantation with use of an autogenous axillary vein valve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433654 TI - In vitro evaluation of endothelial and smooth muscle function of primary varicose veins. AB - Experiments were designed to study functional changes in superficial leg veins of patients with primary varicosity. Excess segments were taken from 19 patients undergoing elective vein resection. Excess segments of greater saphenous veins taken from 13 patients undergoing coronary or lower extremity arterial bypass were used as controls. These rings, some with endothelium deliberately removed, were suspended for the measurement of isometric force in organ chambers. Segments of veins were also evaluated with respect to their total protein content, endothelin content, and histologic structure. In varicose veins, maximal contractions in response to potassium chloride (n = 9), norepinephrine (n = 9), and endothelin (n = 4) were reduced 71.1%, 78.2%, and 75.6%, respectively, compared with contractions in control veins (p < 0.01). In addition, no differences were detected in the maximal tension or tissue sensitivity (EC50) between segments of nonvaricose greater saphenous vein and adjacent varicose tributaries from the same patient. Rings with and without endothelium contracted similarly. In varicose veins, endothelium-dependent relaxations produced by the calcium ionophore A23187 were attenuated 89.7% compared with relaxations in controls (n = 6, p < 0.01). In veins from patients with primary varicosity, endothelium-independent relaxations produced by nitric oxide (n = 6) and forskolin (n = 3) were diminished 86.8% (p < 0.01) and 65.6% (p < 0.05), respectively, compared with relaxations in control veins. In primary varicose veins, protein content was decreased (n = 17, p < 0.01) and endothelin content increased (n = 17, p = 0.1) compared with those values in control veins (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433655 TI - A comparison between descending phlebography and duplex Doppler investigation in the evaluation of reflux in chronic venous insufficiency: a challenge to phlebography as the "gold standard". AB - To evaluate venous reflux in 56 lower limbs of 32 consecutive patients, hemodynamic tests, ascending and descending phlebography, and supine and erect quantitative duplex scanning were performed and the clinical severity was classified (class 0 = 15, class 1 = 19, class 2 = 8, and class 3 = 14). Of the 56 lower limbs, 22 (40%) had severe swelling and hyperpigmentation with or without ulcer (classes 2 and 3). Adequacy of the clinical severity classification was supported by the hemodynamic results. Radiologic and ultrasound findings were described by axial grading, multilevel/multisystem point, and multisegment scoring systems. Applying these evaluation systems, the phlebographic and scan results correlated poorly. There was no relationship between the radiologically obtained average reflux grade or points and the clinical severity. An erect quantitative duplex Doppler test assessed by the multisegment scoring system correlated best with the severity classification. The predictive value of this test to diagnose severe reflux leading to severe symptoms (classes 2 and 3) was 77% compared with 35% to 44% for descending phlebography. The study suggests that erect quantitative segmental duplex Doppler reflects the degree and distribution of venous reflux more accurately than does descending venography. PMID- 1433656 TI - Femoral vein valvuloplasty: intraoperative angioscopic evaluation and hemodynamic improvement. AB - Femoral vein valvuloplasty (FVV) is the operation of choice for primary valvular incompetence, but this procedure is highly operator dependent for judging the competence of the valve repair during surgery. We have reviewed our experience with FVV, focusing on the utility of angioscopic-guided valve repair and hemodynamic results. Nine limbs in six patients underwent superficial FVV. There were four men and two women; the average age was 49 years (range 32 to 62 years). All limbs were Society for Vascular Surgery/International Society for Cardiovascular Surgery clinical stage III (venous ulcer), and descending phlebography showed grade 4 reflux in six limbs, grade 3 reflux in one limb, and grade 2 reflux in two limbs. In addition to FVV, five limbs underwent subfascial ligation of incompetent perforators and three limbs underwent ligation and stripping of superficial varicosities. Two limbs underwent polytetrafluoroethylene wrapping of the valvuloplasty. The last five valvuloplasties underwent angioscopic evaluation of the repair, and the last two procedures were closed valvuloplasties (without venotomy). Follow-up averaged 20.3 months (range 2 to 51 months). In all patients ulcers healed without recurrence. There were two perioperative deep vein thromboses in the polytetrafluoroethylene wrapped repairs. All superficial femoral veins were patent by duplex scanning at the time of follow-up. Venous refill time measured by light reflection rheography did not improve after surgery. Venous filling index measured by air plethysmography showed near normalization (3.83 +/- 0.82) after angioscopically guided FVV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433657 TI - Current use of inferior vena cava filters. AB - To study possible changes in the clinical use of inferior vena cava (IVC) filters caused by the introduction of percutaneous delivery systems, we reviewed all patients who underwent placement of IVC filters at our institution from 1988 to 1991. Eighty-four patients (52 men and 32 women) ranging in age from 18 to 90 years (mean 67 years) were identified. Filters were required because of contraindications to anticogulation in 64% anticoagulation failure in 25%, and preoperative prophylaxis in 11% of patients. The underlying disease was lower extremity deep vein thrombosis in 50% and pulmonary embolism in 45% of patients. Five percent of patients received prophylactic filters without documented thromboembolism. All filters were placed percutaneously by interventional radiologists, 77 through the common femoral vein and 7 through the internal jugular vein. Three types of filters were used. One procedure-related death occurred because of acute IVC occlusion. Fatal pulmonary embolism within 48 hours after filter placement was documented in one patient and suspected in one late death. No other clinically apparent pulmonary embolism or leg swelling occurred after filter placement. Minor complications related to filter placement occurred in 13 patients, but none required operative intervention. Analysis of complication rates of the three filter types was precluded by the small sample size. After a mean follow-up of 11 months, 42 patients (50%) had died of malignancy (n = 25), multisystem organ failure (MSOF; n = 7), cardiovascular events (n = 4), recurrent pulmonary embolism (n = 2), cerebrovascular events (n = 4), or an unknown cause (n = 1). Twenty-three patients (27%) died before hospital discharge.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433658 TI - Physician practices in the management of venous thromboembolism: a community-wide survey. AB - Although there is a broad consensus on the optimum approach to the management of venous thromboembolism, there are few data from which to assess the extent of compliance with these recommendations. A community-wide study was therefore conducted in 16 short-stay hospitals in central Massachusetts to assess the clinical management of venous thromboembolism. Based on validated discharge diagnostic codes, there were 1231 clinically recognized cases of venous thromboembolism, 0.8% of 148,730 discharges in the 18-month period from July 1, 1988, to December 31, 1989. Eighty-one percent of study patients were admitted with signs or symptoms of acute venous thromboembolism. Ninety-seven percent of patients were treated with either heparin, warfarin, or inferior vena caval filter. Intravenous heparin was given to 89% of patients (mean bolus 6674 IU; mean duration 6.6 days). After heparin administration, there was a mean delay of 2.3 days in starting warfarin. Assuming a corresponding decrease in the length of hospital stay, appreciable cost savings could have been realized by earlier start of oral anticoagulation. An inferior vena cava filter was placed in 14% of patients. There was a clinically recognized in-hospital recurrence of venous thromboembolism during treatment in 2% of patients. Despite a slightly lower rate of compliance with recommended treatment regimens in nonteaching hospitals, and despite less frequent use of the inferior vena cava filter, there was no significant difference in the rate of in-hospital recurrence of clinically recognized venous thromboembolism in 10 nonteaching hospitals compared with six teaching hospitals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433659 TI - Frequency of pulmonary embolism in ambulant patients with pelvic vein thrombosis: a prospective study. AB - One hundred thirty-nine consecutive patients (average age 70.1 years) who were able to walk with a swollen leg were seen at the clinic where diagnosis of acute deep vein thrombosis (DVT) extending to the pelvis was confirmed by injecting microspheres labeled with technetium 99m into the dorsal foot vein (radionuclide venography). Thirty-nine (28%) of these patients had malignant disease. Perfusion lung scans performed immediately after radionuclide venography were supplemented by inhalation scans (99mTc-labeled diethylenetriamine pentaacetic acid aerosol) in case of perfusion defects. During scintigraphy patterns highly indicative of pulmonary embolism (PE) were found in 80 patients (58%), but only 11 (7.9%) had minor clinical symptoms. All patients were admitted to the ward, were given standard heparin subcutaneously (35,000 to 40,000 units/24 hr) and firm bandages, and were encouraged to walk. After 11 days pulmonary scintigraphy was repeated and revealed no change in 55 of 59 patients without PE and in 40 of 80 patients with PE. Thirty-three patients (23.7%) showed regression of perfusion defects. New PE developed in 11 patients (7.9%, four without and seven with previous PE). Autopsy revealed that one 80-year-old patient with prostatic carcinoma had died of massive PE. When comparing this frequency of newly developed PE during ambulation with the occurrence of PE after bed rest, according to the literature, it is no more dangerous for a mobile patient with proximal DVT to walk wearing a firm bandage than it is for the patient to be in bed. Therefore we recommend treating mobile patients with DVT by use of anticoagulation and firm compression bandages and without immobilization. PMID- 1433660 TI - Circumferential venolysis and paraclavicular thoracic outlet decompression for "effort thrombosis" of the subclavian vein. AB - Effort thrombosis of the subclavian vein (Paget-Schroetter syndrome) has long been considered a primary thrombotic process, but recent experience suggests that it may commonly result from repeated mechanical compression. Increased awareness of the pathophysiology of this syndrome can allow timely, improved diagnostic screening and the use of specific surgical intervention to relieve the venous consequences. During the past 15 years we have treated six patients with mechanical compression in the thoracic outlet causing surgically correctable venous occlusive problems. There were four men and two women with an average age of 38 years (range 26 to 53 years). All patients exhibited pain, swelling, and cyanosis of the upper extremity, with worsening venous congestion on abduction of the arm. Five of six patients were originally treated for effort thrombosis of the subclavian vein with arm elevation and anticoagulation; two also underwent immediate thrombolytic therapy with urokinase. Venography was prompted in each case by positional symptoms during follow-up and showed irregular stenosis of the subclavian vein adjacent to the first rib. All patients underwent extended first rib resection and circumferential venolysis (one patient underwent bilateral procedures); one was performed through a transaxillary approach, two through a supraclavicular approach, and four through a new, "paraclavicular" approach. All subclavian veins appeared normal after venolysis. Five of six patients also underwent complete scalenectomy and brachial plexus neurolysis. In each patient, venous and neurogenic symptoms resolved and venography confirmed a patent subclavian vein, with follow-up ranging from 11 months to 13 years (mean 3.8 years). PMID- 1433661 TI - Hemodynamic deterioration in chronic venous disease. AB - Clinical deterioration of patients with chronic venous disease (CVD) has been well described and a standardized classification has been proposed. The progressive hemodynamic deterioration producing these clinical findings is less well appreciated. This study examines and correlates venous hemodynamics with clinical severity in patients with CVD. Two hundred seventy-four extremities from 149 patients with varying degrees of CVD and 56 extremities from 28 symptom-free volunteers were evaluated clinically and hemodynamically. Each limb was assessed for functional venous volume, degree of valvular insufficiency, efficiency of the calf muscle pump, and noninvasive estimate of ambulatory venous pressure. In addition, exercise venous pressures were recorded in 56 extremities from 36 patients and 9 extremities from 6 volunteers. As CVD progresses from class 0 to class 2, venous volume expands, valvular function deteriorates, the calf muscle pump becomes inefficient, and ambulatory venous hypertension develops. However, once extremities develop brawny edema or hyperpigmentation, further deterioration of limb hemodynamics does not occur. Patients with deep venous obstruction have more severe valvular insufficiency, calf muscle pump dysfunction, and ambulatory venous hypertension than have patients without evidence of obstruction. Residual volume fraction offers a reliable noninvasive estimate of ambulatory venous pressure (r = 0.76), although its correlation was significantly better for patients without venous obstruction (r = 0.86) than for those with obstruction (r = 0.40; p < 0.05). Deterioration in venous hemodynamics parallels clinical severity through class 2. Once brawny edema and hyperpigmentation occur, ulceration develops without additional deterioration of venous hemodynamics. PMID- 1433662 TI - Long-term effects of superficial femoral vein ligation: thirteen-year follow-up. AB - This study examines the late clinical, hemodynamic, and anatomic results of superficial femoral vein ligation performed in 35 extremities that were followed an average of 13 1/2 years (range, 5 to 22 years). Indications for interruption were to prevent recurrent embolization from distal deep venous thrombosis (14 cases), to prevent emboli in patients with contraindication to anticoagulants (eight cases), to prevent distal reflux in selected patients undergoing iliofemoral thrombectomy (11 cases), and to control reflux in failed venous reconstruction (two cases). Ligation was effective in the prevention of pulmonary emboli as indicated by no significant clinical events and 15 negative postligation ventilation-perfusion scans. Long-term clinical follow-up showed normal (class 0) or near-normal (class 1) extremities in 83%. Fourteen percent developed mild to moderate symptoms of pain or swelling but without ulceration (class 2), and only one case (3%) had ulcerative sequelae (class 3). The only two findings that correlated with worse clinical outcome were the presence of an incompetent profunda femoris or an obstructed greater saphenous vein. Profunda femoris reflux was found in 60% (3/5) of patients with class 2 or 3 sequelae, which was significantly higher than the 14% (3/22) found in those patients with class 0 or 1 results (p < 0.05). Obstruction of the greater saphenous vein was found in 50% of those patients with class 2 or 3 results as opposed to 9% with class 0 or 1 results (p = 0.05). A large collateral vessel between the profunda femoris and the distal superficial femoral or popliteal vein was associated with poor long-term results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433663 TI - Reconstruction of large veins for nonmalignant venous occlusive disease. AB - To evaluate the effectiveness of venous grafting, we reviewed the management and clinical course of 28 patients (21 males and seven females) who underwent 29 reconstructions of large veins for benign disease. There were 12 patients with superior vena cava (SVC) syndrome, two with subclavian vein thrombosis, and 15 with occlusion of the inferior vena cava (IVC) or iliac veins. One of these patients underwent both IVC and SVC reconstructions. Reconstruction of the SVC was performed with spiral saphenous vein graft (SSVG) in nine patients and expanded polytetrafluoroethylene (ePTFE) in three. All seven straight SSVGs had documented patency at a median of 7 months (2 weeks to 5 years) after reconstruction. Six patients had complete relief of symptoms. Two patients with bifurcated SSVG had early occlusion of one graft limb. Two of the three ePTFE grafts needed early thrombectomy. One graft reoccluded at 6 months and two were patent at 2 and 5 years. The two subclavian vein reconstructions with axillary jugular ePTFE grafts with an arteriovenous fistula had documented early patency. Both patients had rapid resolution of symptoms. The IVC or iliac vein was reconstructed with ePTFE graft in 11 patients, SSVG in three, and Dacron in one. A femorofemoral arteriovenous fistula was added in eight patients with ePTFE grafts. Seven of the 11 ePTFE grafts had documented patency at the last follow-up (median 9 months; range 2 weeks to 5 years). None of the three SSVGs had documented long-term patency. The one Dacron cavoatrial graft occluded at 3 years. A straight SSVG continues to be our first choice for SVC replacement. Short, large-diameter ePTFE grafts perform the best in the abdomen. Femorocaval or long iliocaval grafts need an arteriovenous fistula to maintain patency. Long term patency after closure of the fistula is still unknown. Femorocaval grafts with poor venous inflow have limited chance of success. Failed or failing grafts may be salvaged by early thrombectomy. Venous reconstruction to treat selected patients with symptoms with large vein occlusion continues to be a viable option. PMID- 1433664 TI - Long-term results of venous reconstruction after vascular trauma in civilian practice. AB - The natural history of venous reconstruction (VR) in terms of patency and clinical outcome after vascular trauma has not been well documented. This study consists of 32 patients who had VR performed for extremity vascular trauma and were available for long-term assessment (mean follow-up time 49 months, range 6 to 108 months). The types of repair performed were as follows: lateral venorrhaphy (simple repair) (56%), interposition grafting (22%), patch repair (12.5%), and end-to-end repair (9.5%). Seventeen patients underwent venography after the operation with documentation of repair patency in eight patients (46%) and thrombosis in nine (54%). Only two patients had significant clinical edema at follow-up examination. Noninvasive venous evaluation consisted of Doppler ultrasonography, impedance plethysmography, photoplethysmography, and color-flow duplex scanning (CFDS). The photoplethysmography-derived venous refilling time of the injured extremity was 34.9 +/- 16.2 seconds whereas that of the contralateral noninjured extremity was 36.8 +/- 16.1 seconds (p = 0.5). Based on standard criteria for CFDS, 90% of VRs were patent. Eight repairs that were patent in the early postoperative period remained patent on CFDS. Of the nine repairs with early thrombosis, eight were assessed as patent on follow-up CFDS. In conclusion, VR is a durable surgical procedure associated with minimal morbidity, good long term patency, and preservation of venous competence. The natural history of thrombosed VRs appears to be one of thrombus absorption with recanalization. PMID- 1433665 TI - Absorbable suture improves growth of venous anastomoses. AB - Growth of vascular anastomoses is desirable in pediatric vascular surgery, especially in pediatric organ transplantation. Although absorbable suture has been shown to be superior to nonabsorbable suture in permitting growth of arterial anastomoses, the optimal suture material for venous anastomoses has not been established. To examine this in a porcine model, we performed bilateral primary end-to-end anastomoses of transected external jugular veins in 10, 4-week old piglets. In each piglet one anastomosis was constructed with continuous absorbable 8-0 polyglyconate suture, whereas the contralateral anastomosis was constructed with continuous nonabsorbable 8-0 polypropylene suture. After 6 months the veins were excised, pressure fixed at 15 mm Hg for 2 hours, and examined grossly and histologically. Vein diameter was measured by contrast radiography at the anastomosis and 1 cm proximal and distal to the anastomosis. Vein cross-sectional area 1 cm from the anastomosis was similar in the two groups: polyglyconate 95.7 +/- 12.3 mm2 versus polypropylene 95.3 +/- 9.7 mm2. However, polyglyconate anastomoses had greater cross-sectional area (polyglyconate 72.8 +/- 7.9 mm2 vs polypropylene 51.8 +/- 6.0 mm2; p < 0.05). In addition, at 6 months polyglyconate anastomoses had a greater percentage of growth (polyglyconate 207% vs polypropylene 118%; p < 0.05) compared with native vein cross-sectional area (23.7 +/- 0.39 mm2) from control pigs at 4 weeks of age. On histologic examination, polyglyconate had dissolved entirely in six cases and was present but in varying degrees of dissolution in the other four; in contrast, polypropylene was identifiable at all anastomoses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433666 TI - The effects of aortic reconstruction and collagen impregnation of Dacron prostheses on the complement system. AB - Complement activation has been associated with numerous clinical hazards such as platelet aggregation, adult respiratory distress syndrome, and renal dysfunction. The complement system is activated by exposure of different biomaterials to blood. Recently a watertight knitted Dacron aortic prosthesis impregnated with bovine collagen has been developed. One potential disadvantage is that this bovine collagen may activate the complement system and evoke the production of inflammatory mediators. We conducted a prospective randomized trial to study the systemic effects of collagen-impregnated prostheses and of aortic surgery with implantation of Dacron prosthesis on the complement system in the perioperative period and at 3 months after operation. Forty-one patients randomly received either a collagen-impregnated (n = 20) or a nonimpregnated prosthesis (n = 21). Twelve patients who had cholecystectomy served as controls. CH50 consumption and C3a generation were determined to study overall complement activation. Furthermore, C3a/C3 fractions were calculated. Finally, C4 and factor B consumption were determined to evaluate the complement stimulation via the classic and the alternative pathways, respectively. We found significant activation of the complement system during the operation in both the collagen group (CH50 consumption: 40%, p = 0.03; C4 consumption: 74%, p < 0.0001; factor B consumption: 73%, p < 0.0001; C3a/C3 fraction increase: 173%,p = 0.04), and the nonimpregnated group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 71%, p < 0.0001; factor B consumption: 76%, p < 0.0001; C3a/C3 fraction increase: 165%, p = 0.025), with no statistically significant differences between the groups of prostheses. Activation was initiated via both the classic and the alternative pathway. This indicates aortic implantation significantly activates the complement system, but that collagen-impregnated prostheses do not stimulate the complement system any more than its nonsealed substrate. Comparing results in patients with vascular disease with controls, a significantly increased complement activation was observed in the vascular group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 74%, p < 0.0001; factor B consumption: 75%, p < 0.0001; C3a/C3 fraction: 169%, p = 0.002), compared with the controls (CH50 consumption: 71%; C4 consumption: 104%; factor B consumption: 94%; C3a/C3 fraction: 119%, all p = NS), with statistical significant differences between the vascular group and cholecystectomies (CH50: p = 0.005; C4: p = 0.002; factor B: p < 0.0001, and C3a/C3 fraction: NS). This observation demonstrates that aortic surgery with the implantation of a Dacron prosthesis significantly activates the complement system. PMID- 1433668 TI - Aneurysms of the superficial femoral artery: a report of two cases and review of the literature. AB - True "arteriosclerotic" aneurysms of the superficial femoral artery, not associated with generalized dilatation of the common femoral or popliteal artery, are relatively rare. We report our experience with two isolated superficial femoral artery aneurysms and review the previous literature. An 88-year-old woman was first seen with thrombosis of a superficial femoral aneurysm and limb threatening ischemia and had eventual limb loss as a result of occlusion of distal run-off vessels despite surgical revascularization. A 93-year-old man came to us with rupture and was treated with an interposition graft, which resulted in limb salvage. Review of 17 "arteriosclerotic" superficial femoral artery aneurysms in 14 patients whose cases were reported in the literature revealed a complication at presentation in 65%, rupture in 35%, thrombosis in 18%, and distal emboli in 12%. However, limb salvage was 94% and there were no perioperative deaths. Abdominal aortic aneurysms were discovered in 40%. Males (75%) were more common than females, and the average age was 77 years (range 61 to 93). Isolated superficial femoral artery aneurysms are rare and occur at an older average age than do other peripheral aneurysms, but their incidence is anticipated to increase with this growing segment of our population. In the absence of evidence of syphilitic, other infectious, immunologic, inflammatory, or connective-tissue disorders, these and other aneurysms are considered arteriosclerotic in origin, despite the absence of diffuse arteriosclerosis in many cases and controversy regarding the role of arteriosclerosis in their cause.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433667 TI - Interleukin-1 beta and tumor necrosis factor-alpha release in normal and diseased human infrarenal aortas. AB - The presence of chronic inflammatory cells in the adventitia and media of abdominal aortic aneurysms and aortic occlusive disease suggest an immunologic response. The purpose of this study is to determine whether normal or diseased infrarenal aortas liberate the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Twenty-six infrarenal aortic biopsies (5 aortic occlusive disease, 15 abdominal aortic aneurysms, and 6 cadaveric donors) were weighed, minced into small pieces, and incubated in media for 48 hours. Conditioned media was harvested at 48 hours and assayed for IL-1 beta or TNF-alpha with use of an ELISA assay. Comparison of groups was performed with a one-way analysis of variance. The constitutive IL-1 beta produced by abdominal aortic aneurysms was significantly different than that in cadaveric donors (908 +/- 194 pg/ml [SE] vs 100 +2- 30 pg/ml). There was no statistically significant difference between abdominal aortic aneurysms and aortic occlusive disease (908 +/- 194 pg/ml vs 604 +/- 256 pg/ml) or aortic occlusive disease and cadaveric donor (604 +/- 256 vs 100 +/- 30). In time-course studies for the release of IL-1 beta, abdominal aortic aneurysms demonstrated maximal release at 48 hours. IL-1 beta release was augmented by lipopolysaccharide in all categories. A dose response curve demonstrated maximal IL-1 beta release on stimulation with 5 micrograms/ml LPS. Constitutive TNF-alpha production was low, ranging from 13 +/- 1.5 pg/ml in cadaveric donor, to 20 pg/ml in aortic occlusive disease, and 24 +/- 11 pg/ml in abdominal aortic aneurysms. There was no augmentation in TNF-alpha with lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433669 TI - In memoriam Fiorindo A. Simeone, MD 1908-1990. PMID- 1433670 TI - Angioplasty restenosis: need for accurate definitions and controls. PMID- 1433671 TI - Long-term evaluation of composite sequential bypass for limb-threatening ischemia. PMID- 1433672 TI - Subarachnoid hemorrhage after carotid endarterectomy. PMID- 1433673 TI - A piece of my mind. Outside in. PMID- 1433674 TI - Gulf War symptoms remain puzzling. PMID- 1433675 TI - Eleventh annual Science Reporters Conference offers cornucopia of medical research stories. PMID- 1433676 TI - The Public Health Service action plan for women's health: STDS. PMID- 1433677 TI - The Public Health Service action plan for women's health: STDs. PMID- 1433678 TI - Quality assessment of quality improvement programs. PMID- 1433679 TI - Did health care injustice fuel rage, riots? PMID- 1433680 TI - The antiquity and origins of rheumatoid arthritis. PMID- 1433681 TI - Ultrasound surveillance to detect postoperative venous thrombosis. PMID- 1433682 TI - Ultrasound surveillance to detect postoperative venous thrombosis. PMID- 1433683 TI - Group B streptococcal sepsis. PMID- 1433684 TI - HIV in semen. PMID- 1433685 TI - The relation between hospital experience and mortality for patients with AIDS. AB - OBJECTIVE: To determine whether there is an association between mortality and hospital acquired immune deficiency syndrome (AIDS) experience for all AIDS related diagnoses, and to determine whether the association is explained by differences in severity of illness, earlier discharge of terminally ill patients, or differences in resource use. DESIGN AND SETTING: Population-based statewide cohort study. All hospitalizations identified for a cohort of AIDS patients diagnosed during 1987 in 40 Massachusetts hospitals were included. PATIENTS: All women and all male intravenous drug users (n = 151), and a random sample of all male non-intravenous drug users diagnosed with AIDS during 1987 in Massachusetts (n = 149). MAIN OUTCOME MEASURES: Primary end points studied were (1) inpatient mortality and (2) 30-day mortality. Length of stay, cost, and intensive care unit use were also examined. RESULTS: In 806 hospitalizations at 40 hospitals inpatient mortality was 13.2%. Relative risk of mortality at low AIDS experience hospitals was 2.16 (95% confidence interval, 1.43 to 3.26) compared with high AIDS experience hospitals. When logistic regression was used to control for age, sex, race, human immunodeficiency virus transmission mode, severity, payer, admission type, hospital ownership, and teaching status, low hospital experience with AIDS remained a significant predictor of inpatient mortality (relative risk, 2.92; 95% confidence interval, 1.37 to 6.22). Comparisons of 30-day mortality by hospital AIDS experience yielded similar results. Length of stay and intensive care unit use were also significantly higher at low-experience hospitals after controlling for severity of illness (P < .05). CONCLUSIONS: We conclude that mortality of AIDS patients is higher at hospitals with less AIDS experience. This finding is not because of greater severity of illness, differences in discharge patterns of the terminally ill, or less intensive use of resources. PMID- 1433686 TI - A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest. AB - OBJECTIVE: To determine the relative efficacy of high- vs standard-dose catecholamines in initial treatment of prehospital cardiac arrest. DESIGN: Randomized, prospective, double-blind clinical trial. SETTING: Prehospital emergency medical system of a major US city. PATIENTS: All adults in nontraumatic cardiac arrest, treated by paramedics, who would receive epinephrine according to American Heart Association advanced cardiac life support guidelines. INTERVENTIONS: High-dose epinephrine (HDE, 15 mg), high-dose norepinephrine bitartrate (NE, 11 mg), or standard-dose epinephrine (SDE, 1 mg) was blindly substituted for advanced cardiac life support doses of epinephrine. MAIN OUTCOME MEASURES: Restoration of spontaneous circulation in the field, admission to hospital, hospital discharge, and Cerebral Performance Category score. RESULTS: Of 2694 patients with cardiac arrests during the study period, resuscitation was attempted on 1062 patients. Of this total, 816 patients met study criteria and were enrolled. In the entire cardiac arrest population, 63% of the survivors were among the 11% of patients who were defibrillated by first responders. The three drug treatment groups were similar for all independent variables. Thirteen percent of patients receiving HDE regained a pulse in the field vs 8% of those receiving SDE (P = .01), and 18% of HDE patients were admitted to the hospital vs 10% of SDE patients who were admitted to the hospital (P = .02). Similar trends for NE were not significant. There were 18 survivors; 1.7% of HDE patients and 2.6% of NE patients were discharged from the hospital compared with 1.2% of SDE patients, but this was not significant (P = .37; beta = .38). There was a nonsignificant trend for Cerebral Performance Category scores to be worse for HDE (3.2) and NE patients (3.7) than for SDE patients (2.3) (P = .10; beta = .31). No significant complications were identified. High-dose epinephrine did not produce longer hospital or critical care unit stays. CONCLUSIONS: High-dose epinephrine significantly improves the rate of return of spontaneous circulation and hospital admission in patients who are in prehospital cardiac arrest without increasing complications. However, the increase in hospital discharge rate is not statistically significant, and no significant trend could be determined for neurological outcome. No benefit of NE compared with HDE was identified. Further study is needed to determine the optimal role of epinephrine in prehospital cardiac arrest. PMID- 1433687 TI - Management of small abdominal aortic aneurysms. Early surgery vs watchful waiting. AB - OBJECTIVE: To compare two clinical strategies for the management of small abdominal aortic aneurysms (AAAs) less than 5 cm in diameter: early surgery (repair small AAAs when diagnosed) and watchful waiting (measure AAA size every 6 months and repair when the diameter reaches 5 cm). DATA SOURCES: We reviewed data from an earlier longitudinal study of patients with small AAAs to estimate incidence rates of rupture or acute expansion. Estimates for other parameters in the model were obtained by searching the medical literature (MEDLINE, 1966 to present). DATA SYNTHESIS: We constructed a Markov decision tree to compare early surgery with watchful waiting in patients with asymptomatic AAAs less than 5 cm in diameter, with respect to long-term survival in quality-adjusted life years. The average annual rates of rupture or acute expansion for AAAs with a maximal transverse diameter of less than 4.0, 4.0 to 4.9, and at least 5.0 cm, are 0, 3.3, and 14.4 events per 100 patient-years of observation, respectively. At an average rupture rate of 3.3 events per 100 patient-years and an average operative risk for elective surgery (4.6%, 30-day mortality), our model predicts that early surgery improves survival in patients who present with a 4-cm AAA. The benefit of early surgery decreases with increased age at presentation. If the average rupture rate for AAAs less than 5 cm is assumed to be low (eg, 0.4 event per 100 patient-years), watchful waiting if favored, particularly as operative risk increases. The decision in this subgroup, however, is sensitive to possible future increases in operative risk. CONCLUSIONS: In the majority of scenarios that we examined, early surgery is preferred to watchful waiting for patients with AAAs less than 5 cm in diameter. Watchful waiting is generally favored, however, for patients with a low risk of AAA rupture or acute expansion, including those patients who present with very small AAAs (eg, < 4 cm). More accurate data concerning the rupture risk of AAAs less than 5 cm would improve clinical decision making. PMID- 1433688 TI - Latex glove allergy. A survey of the US Army Dental Corps. AB - OBJECTIVE: To assess the prevalence of latex glove allergy in a population of health care providers (dentists) with a high occupational exposure to latex gloves. DESIGN: A survey instrument was distributed to all active-duty dental officers in the US Army (n = 1628). The survey was designed to identify those individuals who had symptoms of allergy to latex gloves. SETTING: US Army dental facilities worldwide. RESULTS: The response rate to the survey was 64% (n = 1043). There were 143 (13.7%) responses indicating latex glove allergy. If nonrespondents were assumed to be allergy-free, the prevalence rate would be 8.8%. CONCLUSION: Latex allergy, as ascertained by self-report in this survey, appears to have a substantial prevalence in this health care provider population. PMID- 1433690 TI - Memorandum to the President-elect. Parameters for health system reform. PMID- 1433689 TI - Experience and outcomes in AIDS. PMID- 1433691 TI - AARP's call to arms: 'reform health care--now!'. PMID- 1433692 TI - Diagnostic and therapeutic technology assessment. Distraction/compression osteosynthesis with the Ilizarov device. AB - Although the Ilizarov device (and technique) to treat problematic fractures and bone deformities has been used since the 1950s in the former Soviet Union, the technique was not introduced to the United States until 1984. Since that time, the technique has become increasingly popular because, in comparison with the alternatives, the Ilizarov technique involves only one surgical procedure and it appears to have fewer complications. In addition, the Ilizarov technique was designed to correct multiple deformities simultaneously. The DATTA panelists thought that the technique was established in terms of safety and effectiveness as a treatment of limb length deformity, bone defects, and angular/rotational deformity of the long bones. The panelists thought that it was promising in terms of safety and effectiveness as a treatment of pseudarthrosis. However, this overall endorsement of the technique was tempered by comments that the technique was associated with a lengthy learning curve, was very labor intensive, and required a large degree of patient cooperation. PMID- 1433693 TI - Primer on allergic and immunologic diseases. PMID- 1433694 TI - The biology of the immune response. PMID- 1433695 TI - Immunodeficiency diseases. PMID- 1433696 TI - Rhinitis and asthma. PMID- 1433697 TI - Anaphylaxis and stinging insect hypersensitivity. PMID- 1433698 TI - Immunotherapy with allergens. PMID- 1433699 TI - Food allergies. PMID- 1433700 TI - Allergic reactions to drugs and biological agents. PMID- 1433701 TI - Allergic skin disorders and mastocytosis. PMID- 1433702 TI - Immunologic aspects of diseases of the eye. PMID- 1433703 TI - Immunologic aspects of granulomatous and interstitial lung diseases and of cystic fibrosis. PMID- 1433704 TI - The autoimmune diseases. PMID- 1433705 TI - Vesiculobullous diseases with prominent immunologic features. AB - It may be very difficult to differentiate between the many bullous skin diseases. Clinical presentation and age of onset can sometimes be helpful. Consultation with a dermatologist may facilitate diagnosis and treatment. More often, information from skin biopsy and immunofluorescent studies, such as DIF, IIF, or split-skin DIF or IIF, is required to make the diagnosis. It is hoped that current investigative studies will elucidate the role of immunoreactants found within the dermoepidermal basement membrane zone in the pathogenesis of these blistering diseases. PMID- 1433706 TI - Immunologic aspects of endocrine diseases. PMID- 1433707 TI - Immunologic aspects of renal diseases. PMID- 1433708 TI - The immunopathogenesis of gastrointestinal and hepatobiliary diseases. PMID- 1433709 TI - Immunologic aspects of neurological and neuromuscular diseases. PMID- 1433710 TI - Immunologic aspects of reproductive diseases. PMID- 1433711 TI - Tumor immunology. PMID- 1433712 TI - Immunohematologic diseases. PMID- 1433713 TI - Plasma cell dyscrasias. PMID- 1433714 TI - Transplantation immunology. PMID- 1433715 TI - Immunization. PMID- 1433716 TI - Immunopharmacology. Immunomodulation and immunotherapy. PMID- 1433717 TI - Use and interpretation of diagnostic immunologic laboratory tests. PMID- 1433718 TI - Future trends in allergy and immunology. PMID- 1433719 TI - Cerebral percutaneous transluminal angioplasty in second year of trials. PMID- 1433720 TI - Alternative therapies study moves into new phase. PMID- 1433721 TI - Dermatology academy drafts skin cancer warning. PMID- 1433722 TI - Healthy workplace: employers, employees benefit. PMID- 1433723 TI - From the Congressional Office of Technology Assessment. PMID- 1433724 TI - From the Centers for Disease Control and Prevention. Public health: surveillance, prevention, and control of nosocomial infections. PMID- 1433725 TI - From the Centers for Disease Control and Prevention. Cigarette smoking among American Indians, Alaskan Natives--behavioral risk factor surveillance system, 1987-1991. PMID- 1433726 TI - From the Centers for Disease Control and Prevention. Plague--United States, 1992. PMID- 1433727 TI - From the Centers for Disease Control and Prevention. Treatment, end-stage renal disease attributed to diabetes mellitus--United States, 1980-1989. PMID- 1433728 TI - Violence in America: time to bite the bullet back. PMID- 1433729 TI - Violence in America: time to bite the bullet back. PMID- 1433730 TI - Violence in America: time to bite the bullet back. PMID- 1433731 TI - Violence in America: time to bite the bullet back. PMID- 1433732 TI - Violence in America: guns. PMID- 1433733 TI - Violence in America: guns. PMID- 1433734 TI - Assault weapons as a public health hazard. PMID- 1433735 TI - Assault weapons as a public health hazard. PMID- 1433736 TI - Assault weapons as a public health hazard. PMID- 1433737 TI - Thermography in breast cancer. PMID- 1433738 TI - The excess incidence of diabetic end-stage renal disease among blacks. A population-based study of potential explanatory factors. AB - OBJECTIVE: To investigate whether the excess incidence of diabetic end-stage renal disease (ESRD) among African Americans could be explained by racial differences in putative ESRD risk factors. DESIGN: Population-based, ecologic study using the 1981 and 1982 Maryland Statewide Household Hypertension Survey for data on risk factor prevalence. PARTICIPANTS: A total of 2.1 million adults residing within the boundaries of the Maryland Regional ESRD Registry, grouped by race and ZIP code into 26 subpopulations. MAIN OUTCOME MEASURE: Incidence rates of treatment for diabetic ESRD between 1980 and 1985 from the Maryland Regional ESRD Registry by subpopulation. RESULTS: Between 1980 and 1985, 442 persons entered treatment for diabetic ESRD. At the level of the subpopulation, diabetic ESRD incidence was positively associated with black race (relative risk [RR], 3.42; 95% confidence interval [CI], 2.84 to 4.13), prevalence of diabetes (RR, 2.35; 95% CI, 1.92 to 2.87), prevalence of poorly controlled hypertension (RR, 1.80; 95% CI, 1.45 to 1.86), lack of a regular source of health care (RR, 1.82; 95% CI, 1.62 to 2.05), and lower socioeconomic status as indicated by lack of college education (RR, 1.41; 95% CI, 1.32 to 1.52) (all, P < .0001). After adjusting for these risk factors, black race remained strongly associated with the overall incidence of diabetic ESRD (RR, 2.70; 95% CI, 1.89 to 3.86; P < .0001). Further analyses suggested that this excess risk among blacks was confined to ESRD related to non-insulin-dependent diabetes (RR, 4.80; 95% CI, 3.09 to 7.46; P < .0001); blacks were at no higher risk than were whites for ESRD related to insulin-dependent diabetes (RR, 0.90; 95% CI, 0.52 to 1.55; P = .70). CONCLUSIONS: These data suggest that the excess incidence of diabetic ESRD among blacks is not fully explained by a higher prevalence of diabetes or hypertension in blacks or by racial differences in age, socioeconomic status, or access to health care. Instead, they suggest an increased susceptibility to ESRD resulting from non-insulin-dependent diabetes among blacks as compared with whites. PMID- 1433739 TI - Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group. AB - OBJECTIVE: To evaluate the contribution of mild to moderate hypertension to progressive loss of renal function by analysis of renal function data from the Multiple Risk Factor Intervention Trial. DESIGN: The cohort of men with mild to moderate hypertension (baseline diastolic blood pressure > or = 90 mm Hg), randomized to a special intervention (SI) group or usual care (UC) group, were examined for change in renal function based on individual reciprocal creatinine slopes over an average of 7 years' follow-up as the outcome measure. Contribution of blood pressure control during follow-up, age, race, and blood pressure at entry were assessed. PARTICIPANTS: The cohort of 5524 (463 black, 5061 nonblack) hypertensive men receiving no therapy at entry provided the data for the present analysis. RESULTS: Blood pressure control was similar for black and white participants, but significant decline in reciprocal creatinine slope was found for black men (mean slope, -0.0090 +/- 0.0013 dL/mg/y) compared with white men (+0.0018 +/- 0.0004 dL/mg/y) (P < .001 for difference between blacks and whites). Decline in renal function was also greater among individuals with elevated systolic (P < .001) as well as diastolic blood pressure (P < .001), and older individuals (P < .001). No difference between the SI and UC groups was seen in reciprocal creatinine slopes, but in both groups combined, treatment that maintained diastolic blood pressure below an average value of 95 mm Hg was associated with stable or improving renal function, whereas participants whose blood pressure remained 95 mm Hg or greater continued to decline at -0.0013 +/- 0.0009 dL/mg/y (P = .007 for difference). Separate examination of the subset of black men (n = 463) failed to show such a difference. CONCLUSIONS: Effective blood pressure control was associated with stable or improving renal function in nonblacks but not in blacks. These findings emphasize the importance of blood pressure control to maintain adequate renal function in hypertensive white men and raise important questions about the relationship of pressure reduction and renal function change in blacks. PMID- 1433740 TI - Percutaneous transluminal coronary angioplasty in New York State. Risk factors and outcomes. AB - OBJECTIVE: To identify significant independent risk factors for major percutaneous transluminal coronary angioplasty outcomes. DESIGN: Retrospective analysis using univariate and logistic regression analysis to identify significant independent risk factors for adverse outcomes. SETTING: All 31 hospitals performing percutaneous transluminal coronary angioplasty in New York State in 1991. PATIENTS: All 5827 patients undergoing percutaneous transluminal coronary angioplasty between January 1, 1991, and June 30, 1991, in New York State. MAIN OUTCOME MEASURES: In-hospital mortality, major complication(s) (in hospital mortality, myocardial infarction, and/or emergency coronary artery bypass graft), and absence of angiographic success (stenosis reduction of less than 20% on any attempted lesion or residual stenosis of at least 50% on any attempted lesion). MAIN RESULTS: Before discharge from the hospital, a total of 37 patients (0.63%) died; 67 patients (1.1%) suffered a myocardial infarction, with a mortality rate of 4.5%; and 97 patients (1.7%) underwent emergency coronary artery bypass graft surgery, with a mortality rate of 2.1% (no deaths in 85 patients who were hemodynamically stable and two deaths among 12 patients who were hemodynamically unstable). A total of 187 patients (3.2%) experienced a major complication. Angiographic success was achieved for 88% of all patients. Multivariate analysis found four independent preprocedural variables related to death: female gender, hemodynamic instability, shock, and ejection fraction. CONCLUSIONS: Percutaneous transluminal coronary angioplasty outcomes in New York compare favorably with other recent results reported in the literature. Several preprocedural variables markedly increase the incidence of adverse events. PMID- 1433741 TI - The changing rate of major depression. Cross-national comparisons. Cross-National Collaborative Group. AB - OBJECTIVE: To estimate temporal trends in the rates of major depression cross nationally. DESIGN: Nine epidemiologic surveys and three family studies. SETTING AND PARTICIPANTS: Approximately 39,000 subjects in population-based samples from nine epidemiologic surveys, and 4000 relatives from three family studies that were conducted independently but using similar methodology in the 1980s in North America, Puerto Rico, Western Europe, the Middle East, Asia, and the Pacific Rim. OUTCOME MEASURES: Age at first onset of major depression by birth cohort and time period. RESULTS: There was an increase in the cumulative lifetime rates of major depression with each successively younger birth cohort at all sites with the exception of the Hispanic samples, in whom the rates in the older cohort (1915 through 1935) were approximately equal to those of the younger cohorts. However, results of fitting statistical models that separate period and cohort effects showed an overall increase in the rates of major depression over time over all countries, although the magnitude of the increase varied by country. The average relative risk of major depression between a particular cohort and the cohort born immediately before varied between 2.6 (95% confidence interval, 1.8 to 3.7) in Florence, Italy, and 1.3 (95% confidence interval, 1.2 to 1.4) in Christchurch, New Zealand. Short-term fluctuations in the rates of major depression during specific time periods and in specific cohorts also varied by country. CONCLUSIONS: Cross-nationally, the more recent birth cohorts are at increased risk for major depression. There are, however, variations in the long- and short term trends for major depression by country, which suggests that the rates in these countries may have been affected by differing historical, social, economic, or biological environmental events. The linking of demographic, epidemiologic, economic, and social indices by country to these changes may clarify environmental conditions that influence the rates of major depression. PMID- 1433742 TI - Thrombolytic therapy of acute myocardial infarction. Keeping the unfulfilled promises. AB - OBJECTIVE: To assess the use of thrombolytic therapy for acute myocardial infarction, evaluating whether inclusion and exclusion criteria should be altered as well as the public health implications of any such alterations. DATA SOURCES: Data obtained were from English-language articles on the use of thrombolytic therapy in acute myocardial infarction. Articles that reported on inclusion and exclusion criteria as well as specific complications of this therapy were specifically sought. The review included articles under the terms thrombolytic therapy and acute myocardial infarction in the National Library of Medicine's MEDLINE database. STUDY SELECTION: Studies selected for detailed review were those reporting specifics about inclusion and exclusion criteria and efficacy. Data extraction guidelines for assessing data quality included study size, patient population, detail of patient information acquired, and consecutive patient enrollment. DATA SYNTHESIS: Thrombolytic therapy can provide substantial decrements of morbidity and mortality of acute myocardial infarction in the subset of patients who receive this therapy, but is underused in the United States. Advanced age per se should not be an exclusion criterion. Improvements can be made in electrocardiographic diagnosis of acute myocardial infarction. Many of the clinical conditions initially excluded from thrombolytic consideration, such as hypertension or having received cardiopulmonary resuscitation, are only relative contraindications. The benefit/risk ratio in treatment of these patients is often acceptable. Several well-documented points of delay from onset of symptoms to treatment can be minimized, and accelerated therapy can result in a reduction in mortality rates. CONCLUSION: Significant public health benefits will result from greater use of thrombolytic therapy in acute myocardial infarction. PMID- 1433743 TI - Can we prevent end-stage renal disease due to hypertension or to diabetes mellitus? PMID- 1433744 TI - The uncertainties surrounding carotid endarterectomy. PMID- 1433745 TI - Sexuality in the patient-physician relationship. PMID- 1433746 TI - The bottom line. PMID- 1433747 TI - Correction facility TB rates soar; some jails bring back chest roentgenograms. PMID- 1433748 TI - Some experts suggest the nation's 'war on drugs' is helping tuberculosis stage a deadly comeback. PMID- 1433749 TI - Surgeons say cutting out some TB and MOTT may be the answer in multidrug resistant infections. PMID- 1433750 TI - From the National Institutes of Health. PMID- 1433751 TI - From the Centers for Disease Control and Prevention. HIV instruction and selected HIV-risk behaviors among high school students--United States. PMID- 1433752 TI - From the Centers for Disease Control and Prevention. Committee on immunization practices: PedvaxHIB lots with questionable immunogenicity. PMID- 1433753 TI - Cancer of the prostate. PMID- 1433754 TI - Cancer of the prostate. PMID- 1433755 TI - Cancer of the prostate. PMID- 1433756 TI - The medical library as a patient aid. PMID- 1433757 TI - The medical library as a patient guide. PMID- 1433758 TI - Active compression-decompression cardiopulmonary resuscitation. PMID- 1433759 TI - A multistate outbreak of Salmonella javiana and Salmonella oranienburg infections due to consumption of contaminated cheese. AB - OBJECTIVE: To determine the source of an outbreak of Salmonella javiana and Salmonella oranienburg infections. DESIGN: Laboratory-based statewide surveillance for Salmonella infections and two separate case-control studies. SETTING: Community- and industry-based studies conducted from May through October 1989. PARTICIPANTS: Thirty-one culture-confirmed outbreak-associated cases of S javiana infection and 60 community controls matched for telephone prefix, gender, and age in case-control study I; 50 cases, 100 community controls, and 64 family member controls in case-control study II. RESULTS: One hundred thirty-six culture confirmed cases of S javiana infection and 11 cases of S oranienburg infection were associated with the outbreak in Minnesota. Outbreak-associated cases were also identified in Wisconsin (15 cases), and in Michigan and New York (one case each). Cases were more likely than controls to have consumed mozzarella cheese manufactured at a single cheese plant (plant X) or cheese that had been shredded at processing plants that also shredded cheese manufactured at plant X (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.7 to 23.2; P < .01). The outbreak-associated strains of both serovars were isolated from two unopened 16 oz (0.45-kg) blocks of mozzarella cheese produced at plant X. The most probable numbers of Salmonella organisms in these samples were 0.36/100 g and 4.3/100 g. CONCLUSIONS: The potential for bacterial pathogen contamination of cheese during manufacture and processing has important epidemiologic implications, particularly because cheese consumption has recently increased in the United States. Low-level contamination of a nationally distributed food product can cause geographically dispersed foodborne outbreaks that may be difficult to detect. PMID- 1433760 TI - An international foodborne outbreak of shigellosis associated with a commercial airline. AB - OBJECTIVE: To determine the source of an international outbreak of shigellosis associated with consumption of food served by a Minnesota-based airline. DESIGN: Cohort studies of players and staff of a Minnesota-based professional football team and passengers on flights with a confirmed case of outbreak-associated Shigella sonnei infection. SETTING: Community- and industry-based studies conducted from October through November 1988. PARTICIPANTS: Sixty-five football team players and staff, and 725 airline passengers in the cohort studies. RESULTS: Twenty-one (32%) of 65 football players and staff developed shigellosis that was associated with consumption of cold sandwiches prepared at the airline flight kitchen (relative risk [RR], 17.1; 95% confidence interval [Cl], 2.4 to 120; P < .001). Confirmed or probable shigellosis was identified among 240 passengers on 219 flights to 24 states, the District of Columbia, and four countries between September 14 and October 13. An outbreak-associated strain of S sonnei was isolated from football players and staff, airline passengers, and flight attendants. Thirty (4.1%) of 725 passengers on 13 flights with confirmed cases had confirmed or probable shigellosis. Illness was associated with consumption of cold food items served on the flights and prepared by hand at the airline flight kitchen (RR, 5.7; 95% Cl, 1.4 to 23.5; P < .01). CONCLUSIONS: This international outbreak of shigellosis was identified only because of the occurrence of an index outbreak involving a professional football team. Prevention of Shigella transmission in mass catering establishments may require reduction of hand contact in the preparation of cold food items or elimination of these items from menus. PMID- 1433761 TI - Cognitive development of Yu-Cheng ("oil disease") children prenatally exposed to heat-degraded PCBs. AB - OBJECTIVE: To compare the cognitive development in Taiwanese children who had been exposed prenatally to high levels of heat-degraded polychlorinated biphenyls (PCBs) with control children who were exposed to background levels. The disorder was called Yu-Cheng, "oil disease," in Taiwan. DESIGN: Matched-pair cohort study. SETTING: Communities in central Taiwan in which there had been a cooking-oil contamination and mass poisoning by heat-degraded PCBs in 1978 through 1979. PARTICIPANTS: One hundred eighteen children born between June 1978 and March 1985 during or after their mothers' consumption of contaminated rice oil; 118 children matched for age, sex, neighborhood, maternal age, and parental education and occupational class; and 15 older siblings of exposed children, born before the poisoning. MAIN OUTCOME MEASURES: Cognitive development measured from 1985 through 1990 using the Chinese versions of the Stanford-Binet test and the Wechsler Intelligence Scale for Children, Revised, RESULTS: The exposed children scored approximately 5 points lower on the Stanford-Binet test at the ages of 4 and 5 years and approximately 5 points lower on the Wechsler Intelligence Scale for Children, Revised, at the ages of 6 and 7 years. Children born up to 6 years after their mothers' exposure were as affected as children born within a year or two after exposure when examined at 6 and 7 years of age. Older siblings resembled the control children. CONCLUSION: Children prenatally exposed to heat degraded PCBs had poorer cognitive development than their matched controls. The effect persisted in the children up to the age of 7 years, and children born long after the exposure were still affected. PMID- 1433762 TI - Misconceptions about cancer among Latinos and Anglos. AB - OBJECTIVE: To collect information regarding knowledge about and attitudes toward cancer in a sample of adult health plan members, self-identified as Latino or Anglo. DESIGN: Cross-sectional survey. SETTING: Prepaid health plan. RESPONDENTS: A random sample of 844 Latinos (mean age, 50.5 years) and 510 Anglos (51.8 years) completed the interview. MAIN OUTCOME MEASURES AND RESULTS: Latinos were significantly more likely than Anglos to think that sugar substitutes (58% vs 42%), bruises from being hit (53% vs 34%), microwave ovens (47% vs 23%), eating pork (31% vs 11%), eating spicy foods (15% vs 8%), breast-feeding (14% vs 6%), and antibiotics (32% vs 12%) could cause cancer (P < .001 for each). Compared with Anglos, Latinos more often misidentified constant dizziness (39% vs 25%) and arthralgias (35% vs 20%) as being symptoms of cancer. A higher proportion of Latinos believed that having cancer is like getting a death sentence (46% vs 26%), that cancer is God's punishment (7% vs 2%), that there is very little one can do to prevent getting cancer (26% vs 18%), that it is uncomfortable to touch someone with cancer (13% vs 8%), and that they would rather not know if they had incurable cancer (35% vs 23%; P < .001 for each). Latino ethnicity was a significant predictor of these knowledge and attitude items in multivariate logistic regression models adjusted for sex, education, age, employment, marital status, county of residence, and self-perceived health status. CONCLUSIONS: We conclude that misconceptions about cancer are more prevalent among Latinos than Anglos and that selected attitudes about cancer among Latinos fit a cultural theme of fatalismo. These data can enable development of culturally appropriate cancer control interventions for Latinos. PMID- 1433763 TI - A critique of the rationale for cancer treatment with coffee enemas and diet. PMID- 1433764 TI - Campylobacter enteritis outbreaks associated with drinking raw milk during youth activities. A 10-year review of outbreaks in the United States. AB - OBJECTIVE: To determine the incidence of recognized outbreaks of Campylobacter enteritis associated with drinking raw milk during youth activities. DESIGN: Retrospective survey of 51 state and territorial health departments. SETTING: The 50 United States and the Territory of Puerto Rico. POPULATIONS: Persons in preschool through college. MEASUREMENT: Information was obtained for all Campylobacter outbreaks associated with consumption of raw milk during youth activities from 1981 through 1990 that were investigated by state and territorial health departments. RESULTS: Twenty outbreaks were identified in 11 states. Four hundred fifty-eight outbreak-associated cases occurred among 1013 persons who drank raw milk, with an overall attack rate of 45%. At least one outbreak was reported for each year of the 10-year period. Fourteen outbreaks (70%) occurred among children in kindergarten through third grade, compared with one outbreak (5%) among fourth through sixth graders. The remaining five outbreaks (25%) occurred in mixed groups of children and teenagers. Only nine (60%) of 15 outbreaks identified from 1981 through 1988 were reported to the Campylobacter national surveillance system maintained by the Centers for Disease Control and Prevention. CONCLUSION: Drinking raw milk on school field trips or other youth activities continues despite the occurrence of multiple Campylobacter outbreaks documented from this practice. Such illnesses can be prevented by educating dairy farmers and officials of schools and youth organizations about the hazards of drinking raw milk. Public health organizations need to develop and implement such educational programs. PMID- 1433765 TI - Induced termination of pregnancy before and after Roe v Wade. Trends in the mortality and morbidity of women. Council on Scientific Affairs, American Medical Association. AB - The mortality and morbidity of women who terminated their pregnancy before the 1973 Supreme Court decision in Roe v Wade are compared with post-Roe v Wade mortality and morbidity. Mortality data before 1973 are from the National Center for Health Statistics; data from 1973 through 1985 are from the Centers for Disease Control and The Alan Guttmacher Institute. Trends in serious abortion related complications between 1970 and 1990 are based on data from the Joint Program for the Study of Abortion and from the National Abortion Federation. Deaths from illegally induced abortion declined between 1940 and 1972 in part because of the introduction of antibiotics to manage sepsis and the widespread use of effective contraceptives. Deaths from legal abortion declined fivefold between 1973 and 1985 (from 3.3 deaths to 0.4 death per 100,000 procedures), reflecting increased physician education and skills, improvements in medical technology, and, notably, the earlier termination of pregnancy. The risk of death from legal abortion is higher among minority women and women over the age of 35 years, and increases with gestational age. Legal-abortion mortality between 1979 and 1985 was 0.6 death per 100,000 procedures, more than 10 times lower than the 9.1 maternal deaths per 100,000 live births between 1979 and 1986. Serious complications from legal abortion are rare. Most women who have a single abortion with vacuum aspiration experience few if any subsequent problems getting pregnant or having healthy children. Less is known about the effects of multiple abortions on future fecundity. Adverse emotional reactions to abortion are rare; most women experience relief and reduced depression and distress. PMID- 1433766 TI - How safe is the food we eat? PMID- 1433767 TI - Molecular genetics and medicine. A call for papers. PMID- 1433768 TI - A piece of my mind. Lasting impressions. PMID- 1433769 TI - Elevated creatine kinase level in postpolio syndrome. PMID- 1433770 TI - Surgery for intracerebral hemorrhage. PMID- 1433771 TI - Use of triple-lumen subclavian catheters for administration of total parenteral nutrition. AB - This study evaluated the safety of triple vs single-lumen catheters in intravenous nutrition. Patients who were judged likely to benefit from a triple lumen catheter were randomized to receive either a single-lumen catheter, with additional peripheral or central venous access as needed, or a triple-lumen catheter. All patients were at increased risk of catheter-related infection because of one or more of the following conditions: > 60 years of age, breakdown of skin integrity, severe underlying illness, diagnosis of acute pancreatitis, recent head or neck surgery, or presence of a preexisting infection. Patients were excluded who had neutropenia, were immunosuppressed, had body burns > 40%, or had contaminated wounds in the subclavicular area. Of 204 patients entered between June 1989 and November 1991, 177 completed the required > or = 7 days of therapy. Seventy-eight of these patients were randomized to a single-lumen catheter and 99 to a triple-lumen catheter. Catheters were inserted and maintained by the Nutrition Support Team. Dressings were monitored daily and changed weekly using a bio-occlusive dressing. When parameters were met for a possible septic episode, simultaneous peripheral and central catheter blood cultures were obtained using the Isolator method. Catheter-related sepsis was considered present if the colony count from a central catheter lumen was > or = 5 times that of the peripheral blood. The incidence of catheter-related sepsis for single-lumen catheters was 2.6% (2 of 78) compared with 13.1% for triple-lumen catheters (13 of 99) (p < .01). No correlation was found with the number of insertion attempts, catheter days, or patient's age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433772 TI - Effect of body positions and splints in bioelectrical impedance analysis. AB - The objective of this study was to evaluate body composition as measured by bioelectric impedance analysis using splints and body positions differing from the standard supine position. Forty-three patients, randomized into two groups of different body positions, and 101 healthy volunteers were prospectively studied. Resistance and reactance of body tissues were measured by bioelectric impedance analysis. Body composition is described by a three-compartment model composed of body fat, body cell mass, and extra cellular mass. The patients were measured in the standard supine position and then randomized into two groups. They were then remeasured with the appropriate splinting device or position change. Volunteers were measured in the standard supine position and all four alternative positions. There was a statistically significant difference demonstrated in whole body resistance, whole body reactance, body cell mass, and the ratio of extracellular mass to body cell mass in some body positions. The percentage of change with different body positions and splints, when compared with the standard supine position, was generally below 2%, a clinically insignificant difference. We conclude that the reliability of resistance and reactance as measured by bioelectric impedance analysis is clinically valid using any of the tested body positions and/or splints. The three-compartment model may be a useful concept to measure body composition changes in both healthy and sick persons. PMID- 1433773 TI - Parenteral glutathione monoester enhances tissue antioxidant stores. AB - Glutathione (GSH) is a potent endogenous antioxidant that protects major organs from oxidant injury. However, present nutrition regimens may inadequately support tissue stores of this tripeptide during critical illness. To determine whether GSH reserves can be enhanced in vivo with intravenous (IV) supplements, rats underwent central venous catheterization, were given chow and water ad libitum during a 2-day recovery period, and were then randomized to receive one of three treatments as an IV bolus: (1) dextrose, (2) glutathione (GSH), or (3) glutathione monoethyl ester. GSH monoethyl ester is transported into cells more easily than is GSH. Tissue and plasma samples were analyzed for GSH at 2 and 4 hours after drug administration. Liver, renal, and ileal mucosal GSH were significantly increased in the GSH-monoethyl ester rats compared with dextrose treated animals. In addition, plasma GSH was dramatically increased after monoester injection. In contrast, GSH administration depressed liver GSH stores and did not significantly affect GSH concentration in the other organs analyzed. Plasma GSH concentration was elevated 2 hours after GSH administration. We conclude that: (1) the monoethyl ester of glutathione can be used in vivo to enhance tissue and plasma GSH concentration and (2) IV GSH administration does not significantly increase tissue GSH levels and may paradoxically depress hepatic GSH in normal rats. Because the malnourished and critically ill are likely to have depleted GSH stores, nutrition strategies that include the provision of GSH monoester may lend additional support to those organs that are at risk for injury from oxygen free radicals during catabolic states. PMID- 1433774 TI - Gastroesophageal reflux in intubated patients receiving enteral nutrition: effect of supine and semirecumbent positions. AB - The incidence of gastroesophageal reflux (GER) in critically ill patients as well as the effect of a nasogastric tube (NGT) and body position as risk factors for GER were determined. Seventy patients with orotracheal intubation receiving enteral nutrition through a NGT for more than 48 hours were prospectively studied with two randomly assigned body positions: supine or semirecumbent. Detection of GER was achieved by scintigraphy after labeling gastric contents with 500 microCi of technetium-99m sulfur colloid administered through the NGT. In 50 patients scintigraphy was performed after subjects had remained in the randomized position for 2 hours with the NGT pinched. Twenty additional patients were studied after the NGT had been removed. In 50 patients with NGT, GER was present in 74% (37 of 50) and was higher in the supine position (81%, 21 of 26) than in the semirecumbent position (67%, 16 of 24), but this difference was not statistically significant (p = .26). In 20 patients without NGT, the incidence of GER was 35% (7 of 20) and it was also higher in the supine (50%, 6 of 12) than in the semirecumbent position (12%, 1 of 8, p = .16). There was a statistically significant difference between GER in patients with and without NGT (74% vs 35%, p = .0002). These data show that there is a high incidence of GER in patients with orotracheal intubation and NGT. The presence of a NGT is a risk factor for GER. Semirecumbency does not prevent GER, but there is less incidence than in the supine position. PMID- 1433775 TI - Parenteral arginine infusion in humans: nutrient substrate or pharmacologic agent? AB - When given as a dietary supplement, arginine enhances lymphocyte mitogenesis and improves nitrogen balance. The purpose of this study was to evaluate arginine's ability to mediate these same effects when given as the sole nitrogen source with minimum additional calories. Thirty patients were randomized to receive 20 g/day arginine hydrochloride or a mixed amino acid solution (Travasol) by intravenous infusion for 7 days after abdominal operations. Mean patient age, body weight, gender ratios, and preoperative degree of weight loss were similar between groups. Mean plasma arginine and ornithine levels rose to 228 +/- 50 mumol/L and 191 +/- 76 mumol/L in the arginine group during infusion. Mean nitrogen balance was -8.8 g/day and -9.2 g/day in the arginine and Travasol groups, respectively. Mean lymphocyte stimulation indices to concanavalin A and phytohemagglutinin fell on postoperative day 1 in both groups. No significant differences in patterns of lymphocyte mitogenesis changes were noted between groups. The mean total number of circulating T cells increased in the arginine group at postoperative day 7. Thus, parenteral arginine infusion in postoperative patients provided comparable nitrogen balance to a balanced amino acid solution but did not increase peripheral blood lymphocyte mitogenesis. When arginine is given parenterally as the sole nitrogen source with minimal additional calories to postoperative patients, no enhancement of mitogen-stimulated lymphocyte proliferation could be demonstrated. PMID- 1433776 TI - Arginine enhances T-cell responses in athymic nude mice. AB - Supplemental L-arginine has been shown to enhance thymic and T-cell responses in rodents. We examined the ability of supplemental dietary L-arginine to induce T cell function in athymic nude mice that lack a normally developed T-cell system. Groups of male nude (nu/nu) mice (Balb/c background) 7 to 8 weeks old were given for 2 weeks 1.2% arginine hydrochloride solution for drinking, whereas controls received acidified tap water. All mice ingested a standard laboratory chow. In the first experiment, the arginine-supplemented animals had significantly greater number of T cells in the spleen (assessed by the number of Thy 1.2-positive lymphocytes) and these cells had enhanced mitogenic responses to mitogenic stimulation (phytohemagglutinin and concanavalin A). In vivo delayed-type hypersensitivity responses to 2,4-dinitro-1-difluorobenzene were also significantly increased after the 2 weeks of arginine supplementation. In a second experiment, mice maintained under the same conditions were skin grafted with rat tail skin. Animals were observed for 100 days for rejection but no significant difference was noted in skin graft survival. We conclude that dietary arginine can increase extrathymic T-cell maturation and function, but cannot induce in vivo allogeneic graft recognition in athymic nude mice. PMID- 1433777 TI - Intravenous glutamine fails to improve gut morphology after radiation injury. AB - Male Sprague-Dawley rats housed in individual metabolic cages received total parenteral nutrients via chronic indwelling internal jugular catheters to determine whether supplementing parenteral nutrition with glutamine would accelerate recovery of small-bowel morphology after abdominal radiation. After recovering from catheter insertion for 3 days they received either 1000 cGy gamma radiation to the abdomen only or no radiation and immediately thereafter received isonitrogenous and isocaloric intravenous solutions containing either 0% or 2% glutamine at 1.58 mL/h for the next 5 days. Intestinal segments were then assayed for whole-bowel deoxyribose nucleic acid content and villus height. Irradiation caused a 40% decrement in these parameters, which were not restored by glutamine supplementation. Therefore, intravenous glutamine supplementation failed to accelerate recovery of small-bowel morphology in this model of combined surgical and radiation injury. PMID- 1433778 TI - Early postprandial energy expenditure and macronutrient use after a mixed meal in cirrhotic patients. AB - The effect of meal ingestion (9 kcal/kg of body weight, 53% carbohydrate, 30% fat, 17% protein, as a liquid formula) on energy expenditure and oxidation rate of carbohydrate, fat, and protein was assessed by indirect calorimetry and urinary nitrogen excretion before and for 3 hours after eating in stable cirrhotic patients and control subjects of comparable age. Postprandial modifications of substrate and hormone levels were also studied. Compared with basal values, the mean +/- SD resting energy expenditure during the first 3 hours after meal ingestion increased similarly in cirrhotic patients (+0.32 +/- 0.12 kcal/min) and control subjects (+0.31 +/- 0.08 kcal/min). Dietary induced thermogenesis was equivalent to 10% of the energy contained in the meal in both groups. Before eating, the carbohydrate oxidation rate was lower and fat oxidation higher in cirrhotic patients than in the control subjects. After eating, glucose oxidation increased whereas fat and protein oxidation rates were reduced in both groups. As a consequence the amount of fat oxidized in the postprandial period remained higher in cirrhotic patients than in the control subjects. After meal ingestion, serum glucose levels increased whereas plasma free fatty acid and glycerol levels decreased in both groups. The substrates, however, remained significantly higher in cirrhotic patients than in control subjects, despite the higher postprandial insulin increment in the patients group, thus suggesting the presence of insulin resistance. Because the postprandial glucose oxidation rate was normal, the low insulin-mediated glucose uptake observed in cirrhotic patients seems to reflect a defect in the nonoxidative disposal of the glucose ingested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433779 TI - Different effects of long-chain and medium-chain triglycerides on glucose oxidation during total parenteral nutrition. AB - This study was undertaken to clarify differences in the effects of lipid emulsions containing either long-chain or medium-chain triglycerides (MCT) on glucose metabolism during total parenteral nutrition (TPN). Glucose kinetics were assessed in beagle dogs using primed, constant infusions of [14C]- and [6 3H]glucose. The rate of appearance of glucose, the percent of VCO2 derived from the oxidation of glucose, the rate of glucose oxidation, and the percent of glucose uptake oxidized were measured at the end of 72 hours of each of the two TPN regimens, ie, TPN in which soybean oil served as long-chain triglyceride comprising 40% of nonprotein calories (L-TPN), and TPN in which tricaprylin emulsion served as MCT (M-TPN). Glucose intake was 5.9 +/- 0.5 mg/kg per minute in L-TPN and 5.8 +/- 0.2 mg/kg per minute in M-TPN. There was no significant difference in the rate of glucose appearance between L-TPN and M-TPN. The rate of glucose oxidation was higher with M-TPN than with L-TPN (p < .05). Not only the percent of VCO2 derived from the oxidation of glucose but also the percent of glucose uptake oxidized tended to be higher during M-TPN than during L-TPN. These findings suggest that the glucose metabolism of dogs receiving L-TPN is different from that of dogs receiving M-TPN. PMID- 1433780 TI - Long-term central venous access vs other home therapies: complications in patients with acquired immunodeficiency syndrome. AB - One hundred and forty silicone catheters were inserted in 127 patients for long term intravenous access with a cumulative follow-up time of 21,125 catheter-days (58 patient-years). Fifty-six patients had acquired immunodeficiency syndrome (AIDS); 44 were not AIDS patients and were receiving ambulatory home parenteral nutrition, whereas the remaining 27 did not have AIDS and were receiving home antibiotic therapy. Patients had a mean of 1.1 catheters inserted, and the rate of Hickman catheter-related sepsis was 0.18 per 100 catheter days or 0.6 septic episodes per patient year of treatment. Catheter-related sepsis was higher in AIDS patients (p < .01) and in patients receiving parenteral nutrition (p < .05) compared with those receiving antibiotic therapy. Prior catheter infection and AIDS were the most significant predictors of catheter infection (p < .01). Staphylococcus aureus was the most commonly isolated pathogen (61%) in AIDS patients. Fever (p < .001) and relative leukocytosis (p < .02) were the most common signs of infection. Only 14 infected catheters (37.8%) were salvaged by antibiotic therapy after the initial infection episode, and 6 of these catheters (42.9%) had recurrent multiple infections. In addition, inflammatory bowel disease was found to be a risk factor for venous thrombosis (p = .018). We conclude that because immunocompromised patients have a high risk of infection, catheter-related sepsis in these patients should be treated by catheter removal and antibiotics. PMID- 1433781 TI - Prefilter and postfilter cysteine/cystine and copper concentrations in pediatric parenteral nutrition solutions. AB - Pediatric amino acid products contain lower concentrations of methionine and require the addition of L-cysteine HCl just before infusion. Reports of a potential interaction between cysteine and copper, a routine addition to parenteral nutrition solutions, have appeared in the literature. This study serially evaluated cysteine/cystine and copper concentrations pre- and postfilter (0.22 microns) in two parenteral nutrition formulations prescribed for normal fluid (NF) or fluid-restricted (FR) pediatric patients. Solutions were infused via a peristaltic pump in vitro for 24 hours. Pre- and postfilter samples were obtained immediately after the infusion began (time 0) and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours during the infusion. At 24 hours pre- and postfilter, cysteine/cystine were quantitated at 87.3% and 85% of the initial concentrations, respectively, for the NF solution and 92% and 91.5% for the FR solution. Pre- and postfilter copper was quantitated at 87.5% and 92.5% of the initial concentrations, respectively, for the NF solution and 88.2% and 95.2% for the FR solution. The 24 hour area under the curve for cysteine/cystine was 88.4% for the NF solution and 96.4% for the FR solution. For copper, the area under the curve for the NF solution was 99% and 96.7% for the FR solution. There was no visual evidence of incompatibility or precipitation. We conclude that copper-containing parenteral nutrition solutions with L-cysteine HCl added immediately before infusion are relatively stable after compounding and infusion over 24 hours. PMID- 1433782 TI - Hypermetabolism and hypercatabolism in Guillain-Barre syndrome. AB - We studied 21 patients with Guillain-Barre syndrome who demonstrated multiple nutritional risk factors upon admission to an intensive care unit: ventilator dependence (71.4%), adynamic ileus (23.8%), significant weight loss in the 2 weeks before admission (53.0%), antecedent viral illness with gastrointestinal sequelae (43.0%), cranial nerve deficits impairing oral intake and gastrointestinal motility (60%), and depressed serum transferrin (85.7%). Patients are hypermetabolic and hypercatabolic because of endocrine, infectious, and inflammatory components of the disease. High-energy (40 to 45 nonprotein kcal/kg), high-protein (2.0 to 2.5 g/kg) nutrition support appears to exert a favorable effect on visceral protein repletion, nitrogen balance, and resistance to pulmonary infection. Immediate attainment of positive energy balance in these hypermetabolic patients, ideally assessed by indirect calorimetry and followed by high-energy, high-protein feedings, may promote positive nitrogen balance early and attenuate muscle wasting in Guillain-Barre syndrome. PMID- 1433783 TI - A simple technique to redirect malpositioned Silastic central venous catheters. AB - A simple and noninvasive method to redirect malpositioned Silastic central venous catheters is described. A syringe is connected to the catheter hub, and burst injections of saline cause the tip of the catheter to flip into the correct intravascular position. The present technique has been applied to more than 30 pediatric patients with excellent results. A detailed description of the technique and case examples are presented. PMID- 1433784 TI - Experimental and clinical applications of molecular cell biology in nutrition and metabolism. AB - Rapid advances in molecular biology have yielded important new techniques for understanding the cellular mechanisms of normal homeostasis and disease. In particular, molecular laboratory methodologies have become important investigative tools for nutritional studies. Detection techniques for specific DNAs, RNAs, and proteins allow direct examination of cellular regulation of protein expression in health and illness. Construction of transgeneic models by recent techniques of inserting foreign genes into experimental animals has provided novel models for studies of cellular metabolism. In addition, molecular biology has had impact on clinical nutrition and therapy. Molecular techniques not only allow for early diagnosis of many inborn genetic errors of metabolism, recombinant technology has also provided for large-scale production of proteins and hormones of potential therapeutic value. The possibility for direct gene therapies is also nearing reality. Hence, understanding the language of molecular biology and the recent developments in this field is not only of research interest, but is also of clinical relevance. PMID- 1433785 TI - Lecithin increases plasma free choline and decreases hepatic steatosis in long term total parenteral nutrition patients. PMID- 1433786 TI - Defining and reporting diarrhea in tube-fed patients--what a mess! PMID- 1433787 TI - Glycylglutamine: metabolism and effects on organ balances of amino acids in postabsorptive and starved subjects. PMID- 1433788 TI - Hepatic cytologic and cholestatic changes in long-term parenteral nutrition. PMID- 1433789 TI - Conversion from continuous to intermittent feedings. PMID- 1433790 TI - Home TPN and AIDS patients. PMID- 1433791 TI - Circulatory indirect calorimetry. PMID- 1433792 TI - Pleural effusion: transudate or exudate. PMID- 1433793 TI - Diagnosis of pleural effusions. AB - Sixty patients of pleural effusion with different aetiology are described. Various microbiological and biochemical parameters were done simultaneously in blood and pleural fluid to differentiate tuberculosis and non-tuberculosis effusions. Some biochemical tests were thought to be helpful in differential diagnosis but no single parameter was found diagnostic. Routine investigations of pleural fluid, sputum and pleural biopsy still remain the best method of diagnosis. PMID- 1433794 TI - Bone tuberculosis in Abbottabad. AB - Eighty patients of bone and joint tuberculosis were diagnosed and treated at DHQ Teaching Hospital, Abbottabad from August, 1987 to December, 1990. Majority of them were children and young adults. There were more females (57.5%) than males (42.5%). A major fraction of the cases were Afghan refugees. Most of the patients were malnourished and belonged to low socioeconomic class. PMID- 1433795 TI - Emotional and behavioural problems among school children in Pakistan. AB - The prevalence of emotional and behavioural problems in school children using Rutters children behavioural questionnaire was 9.3% with antisocial disorders being the commonest one. These disorders are not only present in this culture but also differ in terms of psychopathology with different levels of schooling. The findings are discussed in terms of their relevance to mental health of children with comparison of results from other countries. PMID- 1433796 TI - Adhesion formation to incisional abdominal wound in response to polyamide "6" and polyglactin "910" sutures. AB - Frequency of adhesion formation to laparotomy wound scar in response to absorbable and non-absorbable synthetic sutures and closure technique was studied. Polyglactin "910" (synthetic absorbable) and polyamide "6" (synthetic non-absorbable) sutures were compared employing both mass and layered closure technique. Layered closure with polyglactin "910" closure developed maximum number of adhesions to laparotomy scar. PMID- 1433797 TI - Focal epithelial hyperplasia--a newly discovered disease in north west frontier province of Pakistan. PMID- 1433798 TI - Radiation induced tumour lysis syndrome in a patient with leukaemia. PMID- 1433799 TI - Appearance of a methotrexate binding plasma protein during high dose methotrexate therapy. PMID- 1433800 TI - Prevalence and causes of blindness in Pakistan. PMID- 1433801 TI - Chronic inflammatory demyelinating polyradiculoneuropathy. PMID- 1433802 TI - Diet and cancer. PMID- 1433803 TI - Non-Hodgkin's lymphoma--clinicopathological pattern. AB - A study of histopathological and clinical features of non-Hodgkin's lymphoma in 495 consecutive cases, diagnosed at AFIP during 1984-1989 is presented. Children below the age of 15 years were not included in this study. The relative frequency of non-Hodgkin's lymphoma was 4.29% in our material. Non-Hodgkin's lymphoma was more frequent than Hodgkin's disease, ratio being 2.44:1. Lymphadenopathy (78.78%), fever (33.08%), weight loss (31.62%) and anemia (30.14%) were the main presenting features. New working formulation was used for morphological characterisation. Follicular lymphoma constituted 8.08% of all cases. Follicular lymphoma was seen only in older age whereas diffuse lymphoma occurred in all age groups. Intermediate and high grade lymphoma represented 73.54% of all NHL. Small lymphocytic lymphoma was common in low grade tumours (13.13%). Extra nodal lymphoma was encountered in a significant proportion (21.22%), gastrointestinal tract being the most frequent site. This study outlines certain interesting features of NHL in Pakistan. PMID- 1433804 TI - Gastric ulcer in Karachi. AB - Of 138 endoscopically or surgically confirmed cases of gastric ulcer, 102 (74%) were males and 36 (26%) females. Both sexes were affected most commonly in the 6th decade of life. Pain, vomiting and gastrointestinal bleeding were the major presenting symptoms, with a median duration of 6 months. Cigarette smoking was the most common (44%) addiction and 10% were on analgesics or nonsteroidal anti inflammatory drugs (NSAID). Family history of ulcer was uncommon (2%) and no predilection for any blood group was noted. Among males 53% were skilled workers while 94% of females were housewives. Forty five percent patients were migrants from India and the rest belonged to different provinces of Pakistan. Presentation and behaviour of different sites of gastric ulcers though varied but the results were not significant. Healing rates with H2 receptor antagonists were 33% at 4 weeks and 78% at 8 weeks. PMID- 1433805 TI - Heroin addiction and sex hormones in males. AB - To investigate the effects of illicit heroin abuse on the endocrine system a study was carried out in North West Frontier Province (NWFP) where heroin addiction is prevalent. Sixty-eight subjects were included in this study. Thirty three were untreated heroin addicts visiting "drug abuse treatment centres" in Peshawar and 35 age matched normal males. Urine samples of all addicts showed the presence of morphine. The serum concentrations of testosterone (T) in addicts was 228 ng/ml, leutinizing hormone (LH) 10.7 mlU/ml and folical stimulating hormone (FSH) 4.9 mlU/ml whereas the corresponding values for control males were T 630 ng/ml, LH 14.3 mlU/ml and FSH mlU/ml, respectively. Heroin exerts a depletion effect on T and FSH levels in more or less all the groups studied irrespective of age, amount of heroin intake per day and period of contact with heroin. LH levels remained affected and are within clinically accepted normal range. PMID- 1433806 TI - Prevalence of mutans streptococci and dental caries in Pakistani children. AB - The caries status of two hundred and eighteen 12 year old school children from four schools of Karachi and Lahore was determined through a WHO pathfinder survey. In addition, the levels of mutans streptococci in the sample were estimated in order to define the proportion of children with high and low mutans levels. A mean DMFT of 1.82 (1.67-0.03-0.12), for decayed and filled teeth respectively; 42% were caries free. Four mutans streptococci; 22% had mutans class 0, 22% class 1, 31% class 2 and 25% class 3. The mean DMFT was respectively, 1.0 + 1.23, 0.98 + 1.52, 2.03 + 2.36 and 3.04 + 3.08. The difference was statistically significant. Twenty four children had 5 or more DMF all except two of them, belonging to mutans classes 2 or 3. PMID- 1433807 TI - Simple, efficient and simultaneous determination of anabolic steroids in human urine. AB - A high performance liquid chromatographic method for the determination of free anabolic drug "sustanon 250" (Organon) is developed. Four testosterone esters, propionate, phenylpropionate, isocaproate and decanoate were detected simultaneously and quantitatively in only 15 minutes. The percentage extraction in dichloromethane of the four testosterone esters from doped urine was 88, 87, 89 and 94% respectively. The separation recorded at 254 nm using analytical column ODS-C18 and methanol as an eluent, showed no interference of naturally occurring steroids. This method can be used for pharmacokinetic studies, routine analysis in pharmaceutical industry, routine therapeutic surveillance and in drug abuse by sportsmen. PMID- 1433808 TI - Extradural tumours in children presenting as paraplegia. PMID- 1433809 TI - Otogenic intracranial abscess. PMID- 1433810 TI - Yoghurt (dahi): a probiotic and therapeutic view. PMID- 1433811 TI - Human toxoplasmosis. PMID- 1433812 TI - Subarachnoid haemorrhage and normal CT scan. PMID- 1433813 TI - Carcinoid tumour of gall bladder. PMID- 1433814 TI - Toxoplasma gondii in cerebrospinal fluid. PMID- 1433815 TI - Electrophysiologic changes before onset of ventricular tachyarrhythmias during partial reperfusion following severe myocardial ischemia in dogs. AB - We examined the electrophysiologic changes before an onset of ventricular tachyarrhythmia during partial reperfusion following severe myocardial ischemia. The left anterior descending coronary artery was occluded and cannulated below the occluded portion in 26 dogs. To deplete collateral flow into the ischemic myocardium, retrograde blood flow was induced for 20 min. Then, in all dogs except 7 with ventricular fibrillation during retrograde blood flow, partial reperfusion through collateral flow into the ischemic myocardium was produced by stopping the retrograde flow. Within 2 min of partial reperfusion, sustained ventricular tachycardia (VT) occurred in 7 dogs (group A) and non-sustained VT degenerating ventricular fibrillation occurred in 11 dogs (group B) of the remaining 12 dogs. In 6 dogs of group A and 9 of group B, epicardial conduction block appeared 5.0 +/- 2.2 and 3.5 +/- 1.3 min after ischemia. This was followed by fractionated electrical activities 15.2 +/- 3.2 and 11.7 +/- 3.3 min after ischemia. In group A, the fractionation had a slight change in configuration and a small increase in amplitude before the onset of VT during reperfusion; in group B, new deflections with large amplitude emerged before it. There was a significant difference in the amplitude (0.38 +/- 0.2 vs 0.67 +/- 0.3 mV, p < 0.025) between the 2 groups, although there was no significant difference in the amplitude (0.33 +/- 0.2 vs 0.23 +/- 0.1 mV) of the fractionation just before reperfusion. Our results show that slight improvement in fractionation induces sustained VT, and new deflections induce non-sustained VT degenerating ventricular fibrillation, even during partial reperfusion. PMID- 1433816 TI - Intermittent anterior divisional block and far advanced right bundle branch block induced by vasospasm during exercise testing. AB - A patient is reported in whom exercise induced reversible ischemic left anterior fascicular block and far advanced right bundle branch block. Master's two step exercise test for pre-operative check-up revealed significant ST elevation in leads V1-5, negative U waves in leads V3-5 and fascicular blocks with retrosternal anginal chest pain. Long acting nitrate and nicorandil relieved the fascicular blocks. PMID- 1433817 TI - Long-term follow-up study of three patients with the long QT syndrome. AB - We studied three women with the long QT syndrome. They were aged 42, 52 and 25 years and had experienced recurrent syncopal attacks. We followed case 1 for 17, case 2 for 18, and case 3 for over 6 y. The attacks tended to occur during the premenstrual stage in case 1 and case 2; case 3 often experienced attacks after exercise. The QT(U)c intervals on admission were 0.68, 0.62, and 0.50 in case 1, 2, and 3, respectively. Torsade de pointes followed by ventricular fibrillation was documented in case 1 and case 2. Although each was treated with a beta blocker, none was fully compliant with the regimen. In case 1, estrogen therapy administered to maintain the hormonal balance premenstrually effectively prevented attacks. Despite the inconsistent use of beta-blockers, the attacks in case 1 and case 2 tended to decrease with age. Case 2 experienced no attacks after menopause. Cause 3 took medication consistently and remained free of attacks for over 6 y. Although she discontinued beta-blocker therapy because of pregnancy, she has experienced no attacks to date. These case studies suggest that hormonal status may be important in the development of syncopal attacks in female patients with the long QT syndrome. PMID- 1433818 TI - Segmental asynergy of the left ventricle in a case of tight aortic stenosis associated with mild ischemic heart disease. AB - Emergency aortic valve replacement with double aorto-coronary bypass surgery was performed to treat severe intractable congestive heart failure in an 82-year-old man. Mild circumflex and left anterior descending artery lesions were present and the pressure gradient across the aortic valve was 80 mmHg despite a low cardiac output. The preoperative anteroseptal akinesia seen by two-dimensional echocardiography was normalized after surgery. Thus, even in patients with segmental left ventricular dysfunction, tight aortic stenosis might be present when concomitant mild ischemic heart disease is present. PMID- 1433819 TI - Molecular analysis of the pathophysiology of cardiomyopathy. PMID- 1433820 TI - The studies of cell damaging and cell growth factors which induce cardiomyopathy. AB - We demonstrated that phosphatidylinositide-specific phospholipase C (PLC) activity was greater in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) then in hamster controls (F1b). Inositol trisphosphate (IP3) production was markedly greater in both of the cardiomyopathic hamsters, BIO 14.6 and BIO 53.58. We have also determined the sarcoplasmic reticulum (SR) function of heart. Calcium uptake into SR markedly increased in BIO 14.6. On the other hand, it significantly decreased in BIO 53.58 compared with F1b. It is well known that IP3 stimulates calcium release from SR. In BIO 14.6, calcium release from SR stimulated by IP3 increased, but its effect decreased in BIO 53.58 compared with F1b. These results suggest that PI response may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in the BIO 53.58 hamster the sarcoplasmic reticulum deteriorate in function. It was concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes. The expression of angiotensinogen mRNA was observed in the hamster heart. There was no differences in its expression level between F1b, BIO 14.6 and BIO 53.58. There was no effect of ages on its expression in these hamster hearts. We have also determined the distribution of angiotensinogen in these hamsters. At 4 weeks of age, the immunohistochemical study revealed that angiotensinogen was widely distributed in subendocardium in these hamsters. There was no difference in its distribution between F1b, BIO 14.6 and BIO 53.58. But at 20 weeks old of age its immunoreactivity decreased in BIO 53.58.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433821 TI - Mitochondrial DNA mutations in cardiomyopathy. AB - Deletions and point mutations of mitochondrial DNA (mtDNA) of patients with dilated or hypertrophic cardiomyopathy were analyzed using the polymerase chain reaction and fluorescence-based direct sequencing. The patients included are with hypertrophic cardiomyopathy associated with left ventricular dilatation, a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes (MELAS), and a patient with fatal infantile cardiomyopathy. Deletions were frequently seen in mtDNA in patients with dilated cardiomyopathy. The mtDNA was sequenced and the direct repeat at each edge of deletion was identified as (5'-CATCAACAACCG-3') which was located in the ATPase6 gene and in the D-loop region. In a patient with hypertrophic cardiomyopathy associated with left ventricular dilatation, another mutant mtDNA was found not to have directly repeated sequence, and was revealed to jump from nucleotide position 8,992 to position 16,072 of mtDNA resulting in a 7,079 bp deletion. This patient had unique point mutation in the tRNA genes. A G-to-A transition in the tRNA(Cys) gene (nucleotide position 5,821) at the aminoacyl acceptor stem and an A-to-G transition in the tRNA(Thr) gene (nucleotide position 15,951) were identified. In a patient with MELAS, an A-to-G transition in the tRNA(Leu)(UUR) gene (nucleotide position 3,243) was observed. This mutation was located at the 5' end of the dihydrouridine loop of this tRNA molecule, and would disturb its function. In a patient with hypertrophic cardiomyopathy associated with lactic acidosis, mutations of mtDNA should be suspected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433822 TI - Dilated cardiomyopathy with special reference to humoral immunity. AB - The question of whether the etiology of DCM is immune or autoimmune has been increasingly discussed. Abnormal findings on humoral immunity in DCM were investigated, especially those regarding anti-heart antibodies (AHA), IgG subclasses and soluble interleukin-2 receptor (sIL-2R). The heterophile type AHA was detected in 64.7% of cases by the indirect immunofluorescence technique (IF) with rat heart, by indirect IF with human heart AHA in 57.8% of cases, and by thin-layer chromatogram with human glycolipids AHA in 44% of cases. Also, 57.1% of the specimens were found to bind IgG on perimyocytes by direct IF with biopsy specimens taken from patients with DCM. The epitope of an antigen which reacted with the heterophile type AHA is a Gal alpha 1-3Gal structure. 200 Kd, 70 Kd and 40 Kd antigens were reacted with AHA detected by indirect IF with human heart. The possible mechanisms of AHA in the pathogenesis could be either complement dependent cytotoxicity or interference to cardiac metabolism. The concentration of sIL-2R and IgG3 in sera from patients with DCM were elevated. These results suggest that immunological abnormalities occur continuously in DCM. PMID- 1433823 TI - Negative washout rate of myocardial thallium-201--a specific marker for high grade coronary artery narrowing. AB - A decline is usually observed in the myocardial uptake of thallium-201 in delayed imaging compared with initial imaging. In patients with severe coronary artery disease (CAD), the uptake is sometimes higher in the delayed than in the initial imaging, which is expressed as negative washout rate. To evaluate the diagnostic implications of this negative washout rate the findings of dipyridamole thallium scintigraphy in 582 patients with coronary artery disease were evaluated. The negative washout rate was present in 201 of 582 patients (35%). It had a significant association with high grade coronary artery narrowing of > or = 90%. Sensitivity in detecting patients with this high grade narrowing by negative washout rate was 48%, its specificity was 93%, and its positive predictive value was 94%. Sensitivity to detect individual coronary artery narrowing of > or = 90% did not decrease according to the extent of CAD, with the highest detection in the left anterior descending coronary artery and the lowest in the left circumflex coronary artery. Since patients with high grade coronary narrowing often require coronary intervention, the results of this study suggest the diagnostic importance of negative washout rate in the identification of the particular subset of patients with CAD. PMID- 1433824 TI - Echocardiographic evaluation of pulmonary arterial hypertension in patients with progressive systemic sclerosis and related syndromes. AB - In order to evaluate the usefulness of echocardiography in detection and characterization of pulmonary arterial hypertension (PAH) in scleroderma patients, we performed M-mode, two-dimensional, and Doppler echocardiography in 71 patients with progressive systemic sclerosis (PSS) and related syndromes: mixed connective tissue disease (MCTD) and overlap syndromes. We estimated systolic pressure gradients across the tricuspid valve from the peak velocity of tricuspid regurgitation (TR) by color-flow guided continuous wave Doppler. TR velocities of analyzable quality for gradient estimation were obtained in 28 patients (39%), of whom 12 showed PAH (peak TR velocity > or = 2.5 m/sec). In comparison, analyzable TR was recorded in 19 (35%) of 55 patients with left-sided cardiac disease. None of the 12 with Doppler-estimated PAH showed left ventricular dilatation or decreased fractional shortening by M-mode and two dimensional measurements. Nonsimultaneous cardiac catheterization confirmed PAH in 8 of 9 with Doppler-estimated PAH and in 3 of 12 without analyzable TR who had hemodynamic study. Doppler-estimated right ventricular systolic pressures (RVSP) correlated well with catheterization-measured pulmonary arterial systolic pressures (PASP) (< 0.01). Our results indicate that Doppler echocardiography is useful in detecting subclinical PAH and estimating PASP in patients with collagen vascular disease. The results of pulmonary function studies suggest that PAH in MCTD is mainly caused by pulmonary vasculopathy. PMID- 1433825 TI - Alteration of pulmonary blood flow in tetralogy of Fallot: pre- and postoperative study with macroaggregates of 99mTc-labeled human serum albumin. AB - The pulmonary blood distribution was examined in 17 patients with tetralogy of Fallot (TOF) pre and postoperatively with macroaggregates of 99mTc-labeled human serum albumin. Most of the patients with TOF demonstrated an abnormal preoperative distribution pattern. The abnormalities included not only an unbalanced distribution between the right and left lungs but also a maldistribution of peripheral vessels in each lung. The Right/Left lung counts ratio and Pulmonary Peripheral Index (calculated in order to express the severity of peripheral maldistribution) correlated neither to the diameter nor the cross sectional area of either right or left pulmonary arteries which were measured angiographically. Postoperatively, the pulmonary blood was shunted toward the developed side of the lung which further contributed to maldistribution of blood flow and unbalanced pulmonary growth. Since the patients with an unbalanced pulmonary blood distribution demonstrated a higher right ventricular pressure one year after the operation, a palliative operation facilitating the growth of the underdeveloped side of the lung might be considered as an effective procedure to precede intracardiac repair. PMID- 1433826 TI - The effect of acute hypoxia on left ventricular function with special reference to diastolic function--an analysis using ultrasonic method. AB - In order to evaluate the effect of acute hypoxia on left ventricular (LV) contractility and diastolic function, hemodynamics and LV wall motion were investigated in anesthetized open-chest paced dogs using M-mode or pulsed Doppler echocardiography. Animals were ventilated with 10% oxygen (Hypo 1) and 6.3% oxygen (Hypo 2). LV contractility and diastolic functions were enhanced under "Hypo 1" and at an early phase of "Hypo 2". However, LV functions, both systolic and diastolic, were simultaneously reduced in the presence of hypercapnic acidosis by "Hypo 2". Peak velocities of diastolic rapid filling flow (R) and atrial contraction flow (A) were increased under "Hypo 1", but showed a biphasic change (an increase and a subsequent decrease) under "Hypo 2". The ratio of A/R, known as an index of LV diastolic function, was not altered under hypoxia alone or even under hypercapnic acidosis. Even when hypoxia seems to enhance LV contractility, LV function has already begun to be depressed with a reduction of pH. This seems, however, to be compensated for by LV dilatation and increase in preload, or preservation of left atrial performance. PMID- 1433827 TI - [Japanese Circulation Society meetings. 1988-1991. Abstracts]. PMID- 1433828 TI - [Total intravenous anesthesia vs. regional anesthesia]. PMID- 1433829 TI - [Effect of intravenous pirenzepine on hemodynamics and gastric juice volume as well as pH in surgical patients]. AB - The effects of pirenzepine on blood pressure, heart rate and gastric juice volume as well as pH were evaluated and compared with those after atropine and cimetidine in 54 adult patients divided into five groups. Patients in Groups A, P, AP, AC and ACP received atropine, pirenzepine, atropine plus pirenzepine, atropine plus cimetidine, or atropine, cimetidine plus pirenzepine, respectively. Atropine 0.5 mg and cimetidine 200 mg were given intramuscularly 60 min before induction of anesthesia, and pirenzepine 10 mg was given intravenously 5 min before induction. Gastric juice was aspirated just after, 60 and 120 min after induction of anesthesia. Mean blood pressure and heart rate remained unchanged following intravenous pirenzepine in Group P, whereas heart rate increased significantly in Groups AP and ACP. There were no significant differences in mean volume and pH of gastric juice among the groups just after and 120 min after induction of anesthesia, although gastric volume in Group AC was significantly less than in Groups P, AP and ACP 60 min after induction. Gastric pH increased gradually and gastric volume decreased slightly following intravenous pirenzepine. The incidence of samples with a pH higher than 2.5 was greater in Group AC than in Group P just after and 60 min after induction, whereas there was no difference between the two groups after 120 min. We conclude that intravenous pirenzepine 10 mg is effective to reduce gastric juice volume and acidity, and it should be given at least 60 min before induction of anesthesia. PMID- 1433830 TI - [Ventilation under high spinal anesthesia--the effect of hypotension]. AB - The ventilatory changes during the course of high spinal anesthesia and the effect of hypotension on ventilation during high spinal anesthesia were studied. Spinal anesthesia with hyperbaric tetracaine was applied to 30 patients scheduled for elective surgery. Patients breathed by mask for ten minutes at rest before and after receiving spinal anesthesia. Respiratory parameters were measured in supine position during (1) pre-anesthetic period under resting condition, (2) anesthetic period when analgesia with pin prick extended to T4 level and (3) anesthetic period when analgesia extended to T1 level. The patients were divided into two groups; those with and without hypotension. In hypotension group, tidal volume and minute ventilation decreased significantly for 30% compared with the control values after spinal anesthesia. PaO2 decreased and PaCO2 increased. In non-hypotension group, tidal volume and minute ventilation after spinal anesthesia increased for 10% compared with the control values. In conclusion, hyperventilation tended to occur in patients with high spinal anesthesia unless hypotension was severe enough. Once severe hypotension had occurred, obvious hypoventilation and respiratory irregularity were observed. Decrease of tidal volume and minute ventilation, hypoxia, hypercarbia and increase in VD/VT were significant during hypotension. The results suggest that during high spinal anesthesia severe hypotension causes hypoventilation and if not treated respiratory arrest ensues. PMID- 1433831 TI - [Effect of epidural buprenorphine on postoperative respiratory function]. AB - The effects of epidural buprenorphine on postoperative respiratory function were studied using respiratory inductive plethysmography (RIP) in two groups of patients [(1) 0.1 mg (2) 0.2 mg] after upper abdominal surgery. Buprenorphine 0.1 mg group showed decreased respiratory rate and increased tidal volume. Decreases in the respiratory rate and the tidal volume were seen in buprenorphine 0.2 mg group and continued for 3-4 hrs after the epidural administration. However, there was no severe respiratory depression in either group. It seems that 0.1 mg of epidural buprenorphine may give a satisfactory postoperative pain relief and less respiratory depression, and RIP is a useful method for the measurement of postoperative respiratory function. PMID- 1433832 TI - [Postoperative pain relief by continuous epidural infusion of bupivacaine and buprenorphine]. AB - Continuous postoperative pain relief produced by epidural block with bupivacaine and buprenorphine was evaluated in 12 patients after thoracotomy, 19 patients after upper abdominal surgery, and 14 patients after lower abdominal surgery. Patients initially received 8 ml of 0.25% bupivacaine and 0.1 mg of buprenorphine at recovery room in operating theater and continuously received the mixture of 0.25% bupivacaine and 5 micrograms.ml-1 buprenorphine at a rate of 1 ml.h-1 using a portable pump. About fifty percent of the patients did not need additional narcotics during 48 postoperative hours. About ninety percent of the patients needed one additional narcotics during 48 postoperative hours. The authors conclude that epidural analgesia with the mixture of bupivacaine and buprenorphine produces satisfactory postoperative pain relief. PMID- 1433833 TI - [Changes in myocardial blood flow and systemic hemodynamics during hypotensive anesthesia induced by adenosine triphosphate with or without dipyridamole]. AB - The changes in myocardial blood flow and systemic hemodynamics during hypotensive anesthesia with adenosine triphosphate (ATP) or ATP with dipyridamole (0.5 mg.kg 1) were studied in 20 mongrel dogs anesthetized with 0.7% halothane in 100% oxygen. In both groups, mean arterial blood pressure (MAP) was reduced to 60 mmHg by intravenous administration of ATP. During hypotensive anesthesia, coronary blood flow, myocardial blood flow and cardiac index increased significantly in both groups. Lactic acid and uric acid increased significantly during hypotensive anesthesia in the group 1. Heart rate, MAP, systemic vascular resistance and coronary vascular resistance decreased significantly during hypotensive anesthesia in both groups. Mean pulmonary arterial pressure, pulmonary arterial wedge pressure and central venous pressure showed no significant changes in both groups. Base excess in the group 1 increased markedly compared with the group 2. We conclude that pretreatment with dipyridamole can prevent metabolic acidosis that occurs during hypotensive anesthesia induced by ATP. PMID- 1433834 TI - [Changes in forehead and sole tissue temperature during cardiopulmonary bypass for acquired cardiac disease]. AB - The forehead tissue temperature (FT-T) and the sole tissue temperature (ST-T) were measured and recorded by a deep body thermometer (Terumo Corp.) during open heart surgery. The changes in FT-T and ST-T after cardiopulmonary bypass (CPB) showed two characteristic patterns; the convergence pattern and the dissociation pattern. It is said that the dissociation pattern can notes a poor peripheral circulation. The deverging point of the two patterns was studied in 65 patients with acquired cardiac disease. We divided the patients into two groups taking 3.5 degrees C of the FT-T and ST-T difference (DT) after 2 hour weaning from CPB. The number of the patients in convergence group (group I) was 42, and that in the dissociation group (group II) was 23. The two groups were compared with the DT and the time required for the rise in each temperature from CPB rewarming to CPB weaning. There was no intergroup difference in the DT when the FT-T began to rise upon CPB rewarming. However, the DT was 3.8 +/- 2.3 (mean +/- SD) degrees C in group I and 7.1 +/- 1.8 degrees C in group II when the ST-T began to rise, and 4.2 +/- 2.5 degrees C in group I and 6.9 +/- 1.4 degrees C in group II when the FT-T reached its peak; the figures were significantly lower in group I (P < 0.01). The time required for the rise in ST-T was significantly shorter in group I (14.8 +/- 17.1 min) than in group II (25.8 +/- 14.7 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433835 TI - [Effects of propentofylline on hypoxia-hypoglycemia-induced calcium accumulation in gerbil hippocampal slices]. AB - The xanthine derivative propentofylline (HWA 285) has been reported to show protective effects against neuronal damage induced by cerebral ischemia. In the present study, we investigated the effect of propentofylline on the hypoxia hypoglycemia-induced intracellular calcium accumulation in gerbil hippocampal slices using microfluorometry. When slices were superfused with hypoxic hypoglycemic medium that did not contain propentofylline, an acute increase in calcium accumulation was detected 75-200s (mean latency of 123s) after the start of hypoxic-hypoglycemia. When slices were superfused with hypoxic-hypoglycemic medium that contained 10 microM, 100 microM and 1mM propentofylline, the latency period before acute increase in calcium accumulation was prolonged in all subregions of the hippocampus in a dose-dependent manner: mean latencies in field CA 1 were 146, 168, and 197s after hypoxic-hypoglycemia, respectively. This retardation in calcium accumulation may be involved in the mechanisms by which propentofylline diminishes ischemic injury. PMID- 1433836 TI - [The function of red blood cells under open-heart surgery with extracorporeal circulation without donor blood]. AB - In 18 patients scheduled for open-heart surgery with extracorporeal circulation without donor blood, P50, 2, 3-DPG, intracellular sodium and potassium in red blood cells, and erythrocyte deformability were measured for the purpose of investigating the influence of severe hemodilution on oxygen transport and function of red cells. P50 and 2, 3-DPG in red cells showed no significant changes until the end of cardiopulmonary bypass (CPB). At the end of operation, 2, 3-DPG content decreased significantly without a significant change of P50. This is probably due to the rightward shift of oxyhemoglobin dissociation curve as compensation for the hemodilution without donor blood. On the first postoperative day, P50 value and 2,3-DPG content decreased significantly but returned to previous values on the second day. As the result of changes of red cell sodium contents and deformability, erythrocyte morphology recovered soon after the end of CPB, but the membrane function of red cells was restored a few days later. In conclusion, oxygen transport in red cells may be disturbed after open-heart surgery with extracorporeal circulation without donor blood. PMID- 1433837 TI - [Mathematical simulation of intracranial condition--Part 1. Linear model stimulation]. AB - We developed a linear mathematical model of the intracranial vessels, which reflects changes of the pulse wave (pulse pressure) of intracranial pressure after ligation of the internal jugular vein. The model composed of eight major variables: 1. resistance of arteries, 2. resistance of small arteries and capillary vessels, 3. resistance of veins, 4. resistance of internal jugular and vertebral veins, 5. compliance of arteries, 6. compliance of small arteries and capillary vessels, 7. compliance of veins and 8. intracranial compliance. All variables are presumed to have linear elements and replaced with electrical elements. The model of neck dissection is expressed as the change of resistance of the internal jugular and vertebral veins. Intracranial condition is expressed as the pulse wave (pulse pressure) of intracranial pressure and driving pressure. After unilateral ligation of the internal jugular vein, the pulse wave of intracranial pressure increased 24% and, after bilateral ligation of the internal jugular vein, it increased 55%. After unilateral ligation of the internal jugular vein, the pulse wave of intracranial pressure increased 27%, and, after bilateral ligation, it increased 79%. When intracranial compliance is normal, the respective ratios of pulse wave of intracranial pressure and driving pressure to cross-sectional area decreased, whereas those after increase of intracranial compliance increased. PMID- 1433838 TI - [Integration of informations gained from heterogeneic world of myocardial function and ischemia]. AB - Currently, heterogeneity is the word to describe any inhomogeneous phenomenon observed in the ever changing living creatures. Myocardial function is dynamic in nature which is a summation of many inhomogeneous components. In fact, heterogenic phenomenon has been observed both at cellular and at ventricular levels during myocardial contraction and relaxation. However, this heterogenic behavior of myocardial activities serves as a source of monitoring parameters by which we can grasp what is happening in the patient. Reliance on only one of those parameters would lead to a wrong diagnosis and judgement in the heterogenic world. We, therefore, need to integrate those parameters to form more realistic image about patient's status. We have to have a cut off point to divide what is right and what is wrong. Although the truth may not be reached eventually from heterogeneous informations, an appropriate method to integrate informations in the heterogenic world will aid us to come closer to the reality. PMID- 1433839 TI - [Utility of intra-bladder pressure monitoring during closure of abdominal wall defects in newborn infants]. AB - Recently, it was demonstrated that intra-bladder pressure (IBP) measured through a transurethral catheter accurately reflects intra-abdominal pressure (IAP). We monitored IBP during closure of abdominal wall defects in three newborn infants with gastroschisis. We were able to avoid complications due to increased IAP by keeping IBP below 20 mmHg. IBP correlated well with inferior vena cava pressure (r = 0.93) which reflects IAP. We advocate the use of IBP monitoring as a simple and reliable means of indirectly determining IAP during operations for closure of abdominal wall defects in newborn infants with omphalocele or gastroschisis. PMID- 1433840 TI - [The use of a Swan-Ganz catheter with a fast-response thermistor for the measurement of right ventricular performance during anesthetic management of pheochromocytoma]. AB - We used a Swan-Ganz catheter with a fast-response thermistor to measure the right ventricular ejection fraction (RVEF) during the anesthetic management of two patients with epinephrine-dominant pheochromocytomas. Pre-operatively, one patient received alpha adrenergic blocking agents (prazocine, doxazocine) to control the blood pressure but the other patient did not receive any agents. In the latter patient who did not receive alpha adrenergic blocking agents, right ventricular function was depressed post-operatively in the recovery room. The importance of preoperative preparation with alpha adrenergic blocking agents was confirmed by the reductions in RVEF and RVEDVI (right ventricular end-diastolic volume index) after resection of the tumor. Not only left heart monitoring but also right heart monitoring with RVEF and RVEDVI are recommended for the proper management of a patient with pheochromocytoma. PMID- 1433841 TI - [Simulation in anesthesia]. AB - Simulation in anesthesia is reviewed. Its aim includes education/training, analysis of phenomena, explanation or interpretation of phenomena and instrument checks. It deals with pharmacokinetics/pharmacodynamics of inhalational and intravenous agents, respiration and circulation, action and behavior of anesthesiologists and income analysis. Simulations are accomplished mainly by using computers, yet few use physical models or a physical model combined with computers. For writing this review, CD-ROM's of Medline data were used. Problems in searching literatures through this route are discussed. Finally, the problem of the distribution of softwares is also discussed. PMID- 1433842 TI - [The epidemiology and clinical features of anaphylactic and anaphylactoid reactions in the perioperative period in Japan]. AB - In an attempt to review the Japanese epidemiology of the anaphylactic and/or anaphylactoid reactions in the perioperative period, we investigated 105 cases with clinical features of anaphylactic and/or anaphylactoid reaction, which are reported in the Japanese anesthesiology-related journals from 1952 to 1990. Eighty-nine percent of the cases were reported during the last decade. There were 66 males and 34 females. The majority of the patients were below 60 years of age, and most of the patients were in their teens and fifties. Ninety percent of the patients had no past history of drug-induced allergy nor tendencies of atopy. Ninety-four percent of the patients recovered completely without any sequelae, and 0.95 percent of them recovered with serious complications. Deaths occurred in 4.67% of the patients. Most frequent clinical signs were cardiovascular (91.4%) and cutaneous (84.8%) manifestations. Respiratory, signs appeared in 41% of the patients. Patients are frequently unconscious and covered with drapes, and early signs and symptoms of anaphylaxis can be masked. In 25% of the patients cardiovascular collapse, including cardiac arrest and undetected blood pressure, appeared as the first noticeable sign. Causative drugs were confirmed immunologically in 5.7% of the patients. In other cases, causative drugs were presumed based on clinical course. Causative drugs and presumed causative drugs were varied, including blood and blood products (24 cases), intravenous anesthetics (19 cases), local anesthetics (15 cases), and muscle relaxants (9 cases), which were used generally in the perioperative period. PMID- 1433843 TI - [Influence of nicardipine on the renin-angiotensin system ina hypertensive crisis during operation in elderly patients]. AB - We studied the influence of nicardipine on renin-angiotensin (RA) system in twelve elderly patients, because the suppression of RA system, the decrease in reactivity of its feedback mechanism, and a high probability of arteriosclerosis and hypertension are well recognized in elderly patients. In hypertensive crisis during operation, intravenous bolus injection of nicardipine was done promptly by anesthesiologists in charge. Plasma renin activity (PRA), angiotensin I (A I), and angiotensin II (A II) were measured with RIA methods before administration of nicardipine and after hemodynamics were stabilized. Changes of systemic arterial pressure and heart rate were simultaneously recorded. Concentrations of PRA, A I, and A II were not significantly elevated, whereas systemic and diastolic blood pressures decreased significantly at 5 min, 15 min, 30 min and 60 min after administration of nicardipine. Heart rate was unchanged. But in a few cases there was an increase in PRA and A I. Average total dose of nicardipine was 26.8 micrograms.kg-1 and average fall of blood pressure was 23.9%. In conclusion, we can use intravenous nicardipine safely and stabilize hemodynamics easily without activation of RA system and rebounding of its feedback mechanism. PMID- 1433845 TI - [Effect of isoflurane, enflurane and halothane on hemodynamics during the induction of anesthesia]. AB - The effects of isoflurane(I), halothane(H) and enflurane(E) on hemodynamics of 36 patients (12, 11 and 13, respectively) were studied during the inhalation of 1.5 MAC of each anesthetics before the surgery. Mean arterial pressure(MAP), heart rate(HR), cardiac index(CI), systemic vascular resistance index(SVRI), and stroke volume index (SVI) were measured noninvasively using the automatic blood pressure manometer and the ultrasonic Doppler method (Accucom). MAP decreased with I, E and H, but a larger decrement was observed with E than with H. CI and SVI with H were less than with E. SVRI decreased with I and E but a significant difference was observed between E and H. Each value with I was between those with H and E. These results indicate that isoflurane causes the depression of blood pressure mostly by its effect to decrease afterload during the induction of anesthesia, although its depressing effect is less than that of enflurane. PMID- 1433844 TI - [Interaction of nicardipine and inhalational anesthetics--comparison between enflurane and isoflurane]. AB - The effects of nicardipine 1 mg bolus injection under enflurane anesthesia were compared with those under isoflurane anesthesia. Twelve neurosurgical patients were divided into 2 groups, enflurane group (n = 6) and isoflurane group (n = 6). In all patients anesthesia was induced with midazolam, thiamylal, fentanyl and vecuronium. Anesthesia was maintained with fentanyl, nitrous oxide, pancuronium plus enflurane (enflurane group) or plus isoflurane (isoflurane group). After incision of dura mater, nicardipine 1 mg was given through forearm venous line. For about 30 minutes before and after nicardipine injection, concentration of inhalational anesthetics was kept constant and no drugs were given. Blood pressure (BP), heart rate (HR), rate pressure product (RPP), and serum concentrations of catecholamine and nicardipine were monitored for 30 minutes after nicardipine injection. In isoflurane group, BP decreased more and longer, and increases of HR and serum concentration of catecholamine continued longer compared with enflurane group. Elimination half life of nicardipine was shorter, area under the curve (AUC) was smaller and clearance of nicardipine was larger in isoflurane group than in enflurane group. It was concluded that isoflurane increased the effects of nicardipine, which were BP depression and reflex sympathetic stimulation, than enflurane and that metabolism and elimination of nicardipine were accelerated more by isoflurane than by enflurane. PMID- 1433846 TI - [A study of cerebral circulation following cervical sympathetic ganglion block]. AB - Cerebral circulation following cervical epidural block or stellate ganglion block at the transverse process of the 6th cervical vertebra (C6-SGB) was evaluated by single photon emission computed tomography of inhaled Xenon-133. Cerebral blood flow before and 15 min after both blocks was measured in eight patients after cervical epidural block and ten patients after C6-SGB. Cerebral blood flow decreased slightly following cervical epidural block, but it was not a statistically significant difference. Cerebral blood flow following C6-SGB could be separated into two groups; in one it increased and in the other it decreased slightly. In conclusion, cerebral circulation is not influenced by cervical epidural block, but it is probably affected by C6-SGB. The manner in which C6-SGB increases cerebral blood flow seems that local anesthetics reached the superior cervical ganglion and block it. C6-SGB without superior cervical ganglion block does not influence cerebral circulation, and it only dilates extracranial vessels. PMID- 1433847 TI - [Pulmonary reaction after protamine reversal of heparin in goats and rabbits]. AB - Protamine reversal of heparin is often associated with severe hemodynamic side effects, including pulmonary hypertension in cardiovascular surgery. However, the precise mechanism of this transient pulmonary hypertension is not clear. Recently, it was reported that pulmonary intravascular macrophages (PIM) react avidly with and phagocytize various foreign particles (liposome, latex, red cells). Sheep, goat and pig have a large population of PIM, but rabbit, rat and human have few. To investigate whether the pulmonary reaction after protamine reversal is related to PIM, we compared the pulmonary reaction after protamine reversal between goats and rabbits. We also studied it in patients for cardiac surgery. Protamine sulphate (2 mg.kg-1) was injected in 2.5 min into femoral artery at five min after heparin sodium (200 IU.kg-1) injection in goats and rabbits. Mean pulmonary arterial and peak airway pressures increased significantly after protamine reversal in goat. On the other hand, in rabbit and human, mean pulmonary arterial and peak airway pressures showed no significant changes. Goat was far more sensitive to protamine reversal than rabbit and human. We conclude that PIM may be the main cause of the pulmonary reaction after protamine reversal. PMID- 1433848 TI - [Effect of hypotensive anesthesia on tissue oxygen tension of the heart, kidney and liver]. AB - The effects of hypotensive anesthesia by prostaglandin E1 (PGE1: 8 dogs) or trimetaphan (TMP: 8 dogs) on tissue oxygenation were studied in 16 mongrel dogs anesthetized with pentobarbital. Mean blood pressure (MBP), heart rate (HR), cardiac output (CO), blood gases (BG), the blood flow and tissue oxygen tension of the heart, the kidney and the liver were measured. The blood flow and oxygen tension were measured by electromagnetic flowmeters and by polarographic oxygen electrodes respectively. PGE1 or TMP was injected intravenously to decrease MBP by 30%. MBP, CO, HR and BG of PGE1 were not significantly different with those of TMP. Coronary blood flow decreased for 12% with PGE1 and for 33% with TMP. Though blood flows of the renal and the hepatic arteries were well maintained with PGE1, they decreased for 36% and 34% respectively with TMP. Oxygen tensions of the myocardium (both outer and inner layers) and the liver were well maintained with PGE1. But with TMP, oxygen tension decreased for 23% in outer layer, for 16% in inner layer and for 31% in the liver. Oxygen tension of the kidney remained unchanged with PGE1 and TMP. The results suggest that PGE1 is more useful for the maintenance of the tissue oxygenation than TMP during hypotensive anesthesia. PMID- 1433849 TI - [A relationship between plasma ANP concentration and hemodynamics during PEEP- evaluation by transesophageal ECHO cardiography]. AB - This study was undertaken to find which cardiac function indices as judged by transesophageal ECHO cardiography (TEE) would accurately predict the plasma ANP levels during PEEP. Fourteen patients who underwent orthopedic surgery were the subjects of the study. PEEP 10 cmH2O or 15 cmH2O was added with a PEEP valve during mechanical ventilation under general anesthesia. The cardiac function indices were measured using a 5 MHz TEE probe and plasma ANP levels were evaluated by radioimmunoassay. There were significant reductions in the left atrial diameter, cardiac output and pulmonary venous flow during PEEP, while A/R and CVP were significantly increased. The plasma ANP concentration decreased significantly from 39.2 +/- 4.8 pg.ml-1 at pre PEEP period to 26.8 +/- 3.1 pg.ml 1 at PEEP 15 cmH2O (mean +/- SE, P less than 0.05). However, we could not find any significant correlation between the cardiac function indices and ANP levels. The secretion of ANP from the heart is regulated mainly by stretch tension of the atrium. PEEP increases the pericardial pressure. Therefore, it seems to be difficult to predict the stretch tension of the atrium using TEE under PEEP. PMID- 1433850 TI - [A study of postoperative respiratory function]. AB - The purpose of this study is to investigate the causes of postoperative respiratory failure from the point of view of respiratory movement and respiratory function, using a respigraph. Thirty patients who had laparotomy, thoracotomy or both were studied. A-aDo2 increased after operation. The values recovered slowly in the order of thoracotomy, laparotomy, was thoraco-laparotomy group. Percent vital capacity (% VC), one second timed force expiratory volume (FEV1), and peak expiratory flow (PEF) were suppressed immediately after operations and increased slowly, but showed still lower values even on the 7th day. VT, V min, f, TI/TT, VT/TI and PaCO2 were almost at the same levels among the three groups. Percent rib cage (% of RC) increased and remained high on the 7th day after laparotomy and thoraco-laparotomy, but showed no remarkable changes after thoracotomy. Between A-aDo2 and % RC in laparotomy group, there was a good correlation. Not only FRC but also the change of % RC seemed to have caused postoperative hypoxemia. The movement of the abdomen affected respiratory dysfunction more than the movement of the thorax after thoracic and abdominal surgery. PMID- 1433851 TI - [Intrabiliary pressure changes produced by inhalational anesthetics in dogs]. AB - The common bile duct pressure was studied in dogs under inhalation of 1.0 MAC and 2.0 MAC of halothane, enflurane, isoflurane or sevoflurane. A double lumen catheter was inserted into the common bile duct through the cholecystic duct for the measurement of intraductal pressure in the choledochoduodenal junction. The intra-bile-ductal pressure (IBP) was measured with constant rate infusion methods every 10 minutes for one hour. After obtaining control IBP measurements, 44 dogs received randomly either 1.0 MAC (n = 6 in each group) or 2.0 MAC (n = 5 in each group) of each four inhalational anesthetics, through a non-rebreathing system. The decreases in IBP produced by 1.0 MAC concentrations of four inhalation anesthetics were not statistically significant although there was a decline from control measurements obtained for each group. The elevations of IBP following 2.0 MAC halothane, isoflurane or sevoflurane were significantly depressed and were 38.3 +/- 21.2, 67.5 +/- 23.8, 63.7 +/- 23.7 (%, mean +/- SD) of the control levels, respectively. However, 2.0 MAC enflurane produced no significant decrease in IBP. PMID- 1433852 TI - [Serum concentrations of ranitidine after intravenous administration in geriatric patients under general anesthesia]. AB - The elimination rate of serum ranitidine was investigated in healthy geriatric patients under general anesthesia. The patients (50-90 y.o., ASA classification 1 and 2) were divided into Group 1 (age greater than or equal to 70, n = 9) and Group 2 (50 less than age less than 65, n = 6). Ranitidine (1 mg.kg-1) was administered intravenously after the induction of anesthesia, and the serum concentration was measured at 60 min and 120 min. The biological half life of serum ranitidine in Group 1 was 98.9 +/- 13.8 (M +/- SD) min, which was not significantly different from that of Group 2. The half life correlated with intraoperative urine volume (r = 0.62), but not with intraoperative bleeding or age. The duration of the above effective ranitidine concentration was calculated as about 4 and half hours after its i.v. injection. This indicates that additional administration is necessary for longer operations. PMID- 1433853 TI - [A comparison of the effects of omeprazole with those of ranitidine on intragastric pH and volume in patients for elective surgeries]. AB - This study compared the effect of omeprazole with those of ranitidine on intragastric secretion during perioperative period. Thirty-one patients were randomly allocated to three groups. Each group received either omeprazole, ranitidine orally or one on the night before surgery. Intragastric pH and volume were measured after induction of anesthesia. Omeprazole group and ranitidine group had a higher mean pH than control group (P less than 0.01). None of the omeprazole group had an aspirate of pH lower than 2.5. One patient (10%) in the ranitidine group and five patients (50%) in the control group and five patients (50%) in the control group had aspirates of pH lower than 2.5. Mean gastric volume was not significantly different among these groups. A single dose of omeprazole 20 mg significantly decreased the number of patients at risk of aspiration pneumonitis. PMID- 1433854 TI - [Use of omeprazole for premedication]. AB - Omeprazole, a proton pump inhibitor was used for premedication for general anesthesia, and its effects on gastric secretion and serum gastrin level were investigated in 60 patients. The patients were divided into the following 4 groups and each group received one of the following medications; (I) a tablet of omeprazole 20 mg before sleep at the night before the surgery, (II) a tablet 2 hours before the induction of anesthesia, (III) one on the night before and another tablet 2 hours before the induction, or (0) no tablet. In the patients who received any dose of the drug, the volume of gastric juice at the beginning of the surgery was significantly less than that in those who received no drug (P less than 0.05). Gastric pH showed a tendency to increase depending on the dose of omeprazole (0 less than I less than II less than III), but it was not significant. No significant change in serum gastrin level was observed in this study. A 20 mg omeprazole tablet may not be adequate as the premedication for general anesthesia. PMID- 1433855 TI - [Anesthetic management of a patient with right ventricular myxoma]. AB - Right ventricular myxoma in a 79 year old male, whose pulmonary trunk was obstructed by the myxoma, was reported. Myxoma of the heart is rare, and especially right ventricular myxoma is rare. Myxomas of the heart have been reported by thirty-seven authors, but right ventricular myxoma has been reported by only one author. Anesthesia for the removal of right ventricular myxoma must be carried out carefully, because some critical troubles may happen during anesthesia for the resection of the right ventricular myxoma. Particularly, occlusion of the pulmonary artery is the most dangerous complication. PMID- 1433856 TI - [Perioperative management of a patient with transient polyuria]. AB - Perioperative and anesthetic management of a patient with a diabetes insipidus is reported. A 33 year old man was followed by physical therapy after spinal cord injury. At that time polyuria (4300-8600 ml.day-1) and polydipsia developed. His urine output was controlled by DDAVP (desmopressin) preoperatively. As the result of water restriction test and Carter-Robbins test the diagnosis of complete central diabetes insipidus was doubted preoperatively. We investigated the changes of his perioperative body fluids and endocrine responses. The following conclusions are made: 1) The diagnosis of this case is not renal and true diabetes insipidus, but is probably partial or transient diabetes insipidus. 2) These results indicate that endocrine examinations related to AVP secretion are essential. PMID- 1433857 TI - [Pneumothorax during laparoscopy]. AB - A 28-year-old female was scheduled for laparoscopy under general anesthesia. Her history and physical examination were unremarkable. Trachea was intubated uneventfully following intravenous administration of thiopental 200 mg and vecuronium 8 mg. Anesthesia was maintained with 40% O2, 60% N2O and sevoflurane. Shortly after pneumoperitoneum was introduced, airway resistance increased and breathing sounds were hardly audible over the right side of the chest. A chest radiograph showed the right pneumothorax. Immediately after evacuating the peritoneal gas, the chest radiograph and a blood gas analysis showed that the pneumothorax had improved. Pneumothorax can occur subsequently to pneumoperitoneum due to passage of gas through weak points or defects in the diaphragm. Breathing sound should be monitored carefully during the laparoscopic surgery. Anesthetic gas analyzer and capnometer are considered to be useful to confirm the cause of the pneumothorax. PMID- 1433858 TI - [Anaphylactoid reactions to contrast media which occurred during cholecystectomy and subsequent disseminated intravascular coagulation--a case report]. AB - A 67-year-old woman without any history of allergic episode developed severe hypotension (40 mmHg) without skin rash one minute after the administration of amidotrizoic acid for intraoperative cholangiography during thoracic epidural and light general anesthesia. Although ephedrine, methoxamine, dopamine and norepinephrine were administered, severe hypotension persisted for three hours and epinephrine was only effective. Marked elevations of serum levels of histamine, leukotriene D4 and leukotriene E4 were noted after the episode, suggesting the occurrence of the anaphylactoid reaction to amidotrizoic acid and the activation of the immunological complement system. After the recovery from the anaphylactoid reaction, the patient developed disseminated intravascular coagulation (DIC) and severe bleeding around the wound for which reoperation was needed. It is necessary to consider some prophylactic treatments against DIC when severe anaphylactoid reaction occurred. PMID- 1433859 TI - [Cardiac herniation after right pneumonectomy]. AB - Cardiac herniation is a rare, but highly lethal complication of intrapericardial pneumonectomy for progressive carcinoma of lung, and occurs in early postoperative period. Our patient with this complication presented sudden onset of severe hypotension and cyanosis after several ventricular premature beats. We suspected cardiac herniation as we observed dilatation of cervical veins and rightward deviation of heart sound. The patient was immediately positioned on his left side and systemic blood pressure increased soon. After verification of the incident by chest X-ray film, emergency operation was performed. Fortunately, vital signs were stable during and after reoperation and the patient could survive. PMID- 1433860 TI - [Herpes zoster of the right cervical region associated with right facial nerve palsy and hoarseness]. AB - A 69-year-old man was suffering from herpes zoster on his 2nd and 3rd right cervical spinal segments and 3rd branch of the trigeminal nerve. He came to our hospital on his 10th illness day and was treated with continuous cervical epidural block, intravenous infusion of acyclovir for five days, and oral paramethasone and Vitamin B12. Oh his 18th illness day, right facial nerve palsy and hoarseness became clear. His cerebrospinal fluid showed no abnormality except cell count 23 x 3 mm-2. No clear paralysis of vocal cords was detected on laryngoscopy. He was also treated with right stellate ganglion block starting on his 21st illness day. His pain and facial nerve palsy recovered completely by his 68th illness day, but hoarseness continued about two months. The hoarseness might be a result of spread of the disease 1) by cerebrospinal fluid, 2) by contact with the 3rd cervical nerve and vagal nerve via accessory nerve, and 3) direct effect on the vocal cords and the muscles controlling them. Herpes zoster on the head and neck region shows various complications and we should follow its course cautiously. PMID- 1433861 TI - [Transient second-degree A-V block during an epidural procedure]. AB - A 26 year old pregnant female had a left ovarian tumor and was scheduled to have an operation. No specific complication was noted preoperatively except pregnancy of 16 weeks and one day. Spinal anesthesia for the operation and continuous epidural catheter placement for postoperative pain relief were planned. During the epidural procedure on L2-3 under left lateral recumbent position, patient developed a bradycardia when the tip of Tuohy needle touched the 3rd lumbar bone (lamina arcus vertebrae). This bradycardia occurred three times and the last episode was recorded on the ECG (Fig 2). Blood pressure at this period was 82/44 mmHg, but patient did not complain any discomfort. The recorded ECG showed II degree A-V block (Wenkebach type). We considered this A-V block is probably due to sharp pain from touching of Tuohy needle on the lamina arcus vertebrae. This kind of periosteal pain is sometime associated with vagal stimulation and it could produce II degree A-V block. During a spinal or epidural procedure, ECG should be monitored and we have to pay attention to these kinds of arrhythmia to prevent more profound hemodynamic changes. PMID- 1433862 TI - [Pulmonary embolism was suspected during hip surgery under spinal anesthesia: a case report]. AB - Most of the lower leg surgeries are done under spinal anesthesia. This 53 year old male had undergone a surgery for his left hip fracture previously and was scheduled for the removal of the screw. Spinal anesthesia was administered and sensory block was obtained up to T8. After the removal of the screw, he coughed weakly for several times. Suddenly ECG monitor showed severe bradycardia and hypotension was observed. He complained of chest pain, dyspnoea and went into shock. Immediately after giving atropine 0.5 mg iv, ephedrine 8 mg x 2 was necessary to raise his heart rate. About 3 minutes later he recovered from his shock state. ECG changes were transient and the bradyarrhythmia during his shock turned out to be AV dissociation. Arterial blood gas analysis showed decreased PaO2 and increased PaCo2. We suspected lung embolism. However, postoperative chest X-ray and pulmonary perfusion scans were within normal limits. PMID- 1433863 TI - [Three cases of irritable bowel syndrome treated with stellate ganglion block]. AB - We examined three patients with irritable bowel syndrome (IBS) who did not respond to drug therapy and who were treated by stellate ganglion block (SGB) alone. The clinical symptoms improved by the SGB in all these three patients. There was no recurrence. The pathophysiological mechanism of this disease and the therapeutic efficacy of SGB should be elucidated with respect to the autonomic nervous, endocrine and immune systems. These results suggest that SGB therapy is effective for IBS, a typical psychosomatic disease. PMID- 1433864 TI - [Evaluation of efficacy of a disposable monitor for surface temperature (PROCHECKER) compared with thermography]. AB - We evaluated efficacy of a disposable monitor for surface temperature (PROCHECKER) compared with thermography. Changes in surface temperature after epidural block with mepivacaine 1% were measured using both PROCHECKER and thermography. Measured areas were regions of bilateral Th 4, 6, 8, 10, 12 and along the midmammary line. The surface temperatures on all areas were measured before, 15 min after and 30 min after the epidural block. Discrepancies of the temperatures measured by the two methods were found in 16.7% of all measured areas, and discrepancies in changes in the temperature were found in 6.7%. In conclusion, a disposable monitor for surface temperature (PROCHECKER) is effective and sensitive to measure changes in the temperature. PMID- 1433865 TI - [Hypoventilation due to disconnection of the vaporizer and negative-pressure leak test to find disconnection]. AB - Most of Ohmeda anesthesia machines have a outlet check valve located in the low pressure circuit, and this influences the type of leak test greatly. We report a case of hypoventilation due to a gas leakage from the junction of two vaporizers, Fluotec 3 and Enfluratec of Ohio 30/70. This gas leakage was not discovered preoperatively by performing traditional leak test of squeezing the bag filled with oxygen. Following intubation of the trachea the patient was paralyzed and mechanically ventilated. Her vital signs were stable and operation was started. Soon thereafter, she became hypertensive in spite of increases in concentration of enflurane and supplemental doses of fentanyl and diltiazem. ETCO2 showed 7.4% and spontaneous respiration started. We checked anesthesia machine and found a gas leakage at the junction of two vaporizers. Anesthesia machine was exchanged. The remainder of the procedure was uneventful and the patient showed a normal recovery. The outlet check valve closes when back-pressure is exerted on it, and a vulnerable area including flow tubes and vaporizers is not tested by the traditional positive-pressure leak test squeezing bag. Ohmeda recommends the use of a negative pressure leak test with suction bulb device. We propose manufacturers to place a cation on anesthesia machine such as -- "Negative pressure leak test is inevitable because of presence of outlet check valve." PMID- 1433866 TI - [Translation of Tabulae Anatomicae in the 19th century and international competition]. PMID- 1433867 TI - [Suppressive effect of sevoflurane on somato-sympathetic reflexes in cats]. AB - Effects of sevoflurane on the reflex activity of the sympathetic nervous system in cats were investigated by observing alteration of the amplitudes of somato sympathetic medullary reflex potentials. These reflex potentials consist of two components, A- and C-reflex potentials, which are induced from the lumbar sympathetic trunk by electric stimulation of the ipsilateral femoral nerve. It is known that A- or C-reflex potential is induced by stimulating peripheral A-fiber group or C fiber group, respectively. Sevoflurane 1, 2 and 3% in oxygen for 30 minutes for each concentration by incremental fashion, were inhalated. Neither A nor C reflex potentials were suppressed by 1 and 2% sevoflurane but 3% sevoflurane caused a significant suppression of both reflex potentials in brain intact cats. Concentration-dependent suppression of C-reflex potentials and a tendency of concentration-dependent suppression of A-reflex potentials were observed in decerebrate cats. Mean arterial blood pressure showed a concentration dependent decrease in both brain intact and decerebrate groups. These results indicate that sevoflurane with concentrations higher than 1 MAC (2.5% for cats) significantly suppresses somato-sympathetic reflex activities. The results suggest, however, that this agent with concentrations lower than 1 MAC suppresses the descending inhibitory system from supra-medullary centers so that the integrated sympathetic outflow from the medulla oblongata are not suppressed significantly. The results also suggest that direct depressive effect on the cardiovascular system by sevoflurane rather than through suppressive effect on sympathetic reflexes may play a major role in hypotension during inhalation of concentrations below 1 MAC. PMID- 1433868 TI - [Effect of prostaglandin E1 on peripheral body temperature in pediatric patients after open heart surgery]. AB - The effect of prostaglandin E1 was studied to examine if it works favorably for peripheral circulation in pediatric patients after cardiac surgery. Dose of 0.1 mcg.kg-1.min-1 increased temperature of dorsal pedis significantly. Difference of temperature of dorsalis pedis and that of rectum was significantly smaller than that in control group. A significant increase in heart rate and a decrease in systolic arterial pressure produced no clinical side effects. We conclude that prostaglandin E1 is a useful and safe vasodilator for circulatory management of pediatric patients after cardiac surgery. PMID- 1433869 TI - [The effects of prostaglandin E1 on renal function]. AB - The effects of prostaglandin E1 on renal function were studied in surgical patients under general anesthesia. The patients were over 20 years old, and had ischemic heart disease, hypertension and/or liver dysfunction. In 67 patients (PGE1 group), prostaglandin E1 (PGE1) was in fused at a rate of 0.02 mcg.kg-1.min 1. In 55 patients (control group), only lactated Ringer solution was infused at a rate of 10 ml.kg-1.h-1. Urine output and fractional sodium excretion in PGE1 group were significantly higher than those in control group. There were no significant differences in creatinine clearance and free water clearance between the two groups. The increase in urine output in PGE1 group could be attributed to the decrease in the water reabsorption in the proximal renal tubule. PMID- 1433870 TI - [Effects of deliberate hypotension on the ischemic heart during isoflurane anesthesia--a comparison of prostaglandin E1 and sodium nitroprusside]. AB - The effects of hypotension induced by prostaglandin E1 (PGE1) or sodium nitroprusside (SNP) on regional myocardial function and metabolism were studied in a canine heart with coronary artery stenosis. Ultrasonic dimension technique was used to assess left ventricular performance. Fourteen open-chest mongrel dogs were anesthetized with isoflurane and mean aortic pressure was maintained at approximately 80 mmHg. The left circumflex coronary artery blood flow was reduced by 40% using a screw flow regulator without affecting global and regional myocardial function. The severity of stenosis was considered almost critical. PGE1 (n = 7) or SNP (n = 7) was administered to reduce mean aortic pressure to 50 mmHg. There were no significant differences between PGE1 and SNP regarding their effect on systemic hemodynamics. Nevertheless SNP decreased percent segment shortening in the stenosed area from the pre-hypotension value more significantly than PGE1 (55.0 +/- 10.8% versus 24.2 +/- 7.3%). This suggests that regional myocardial ischemia is more deteriorated during SNP-induced hypotension. It seems that PGE1-induced hypotension is safer when it is applied to patients with coronary artery disease. PMID- 1433871 TI - [Effects of high-dose fentanyl anesthesia on auditory brain stem responses]. AB - It was previously reported that high-dose (50 micrograms.kg-1) fentanyl anesthesia had no effect on auditory brainstem response (ABR). However, the effect of the dose of 100 micrograms.kg-1 of fentanyl is unknown. We examined the effects of the dose of 50 micrograms.kg-1 and 100 micrograms.kg-1 of fentanyl on ABRs in 10 patients scheduled for cardiovascular surgery. No significant change was observed immediately after infusion of 50 micrograms.kg-1 of fentanyl, but peak latencies of waves I, III and V were significantly prolonged and the amplitude of wave V was significantly decreased immediately after infusion of 100 micrograms.kg-1 of fentanyl. The interpeak latencies of I-III and I-V were not affected. Therefore, prolongations of latencies of waves III and V were due to the change of latency of wave I. These results demonstrate that high-dose (100 micrograms.kg-1) fentanyl anesthesia depresses the peripheral auditory perception but dose not depress the central conduction. PMID- 1433872 TI - [The anesthetic effects of steroids and their actions on the properties of model membrane]. AB - The action of anesthetic steroid on the GABAA receptor in the postsynaptic membrane has been suggested as a mechanism of steroid anesthesia. Alphaxalone, the main component of althesin, is a strong anesthetic, whereas its analogue, delta 16-alphaxalone is not. The only structural difference between the two is a presence of the double bond in the D ring of delta 16-alphaxalone. The effects of these steroids on the model membrane structure and the hydrogen bonding between lipid membrane and water were examined by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) and compared with their anesthetic potencies in goldfish. Alphaxalone decreased the phase-transition temperature from the solid-gel to the liquid-crystal state of DPPC liposome. FTIR showed that alphaxalone molecules released the bound water molecules in the lipid water interface of D2O-in-CCl4 reversed micelles. delta 16-alphaxalone in high concentration was also an anesthetic in goldfish. It also showed a weak effect on the phase-transition temperature and the hydrogen bond breaking activity. These changes in the membrane properties correlated to the anesthetic potency. These results suggest that anesthetic potency of steroids is related to their action in destabilizing the structures of the water molecules in the macromolecule-water interface and the macromolecules. PMID- 1433873 TI - [The effect of isoflurane or sevoflurane on circulating blood volume--a study under controlled ventilation]. AB - Changes of circulating blood volume during isoflurane or sevoflurane anesthesia were investigated by the dual indicator dilution method in eighteen mongrel dogs. The animals were randomly divided into three groups; control (C) group n = 6, isoflurane (I) group n = 6, and sevoflurane (S) group n = 6. The values of circulating blood volume (ml.kg-1) at 0, 0.5 and 1.0 MAC period were 90.1 +/- 18.7----87.5 +/- 17.2----94.1 +/- 23.6 in the I group and 91.6 +/- 12.5----96.5 +/- 15.0----94.1 +/- 8.5 in the S group, respectively. No significant changes were found in both groups concerning circulating blood volume, red cell volume, and plasma volume, but circulating blood volume and plasma volume tended to increase slightly in both groups at 0.5 and 1.0 MAC period compared with 0 MAC period. Mean arterial pressure decreased 68% of the initial value in the I group at the 1.0 and 78% stages in the S group. Cardiac index tended to increase from 2.6 +/- 0.4 l.min-1.m2 to 3.2 +/- 0.9 in the I group at the stage 1.0 but to decrease from 5.2 +/- 1.4 l.min-1.m2 to 4.1 +/- 0.9 in the S group. It was suggested that the increase of venous pressure resulted in the significant decrease of plasma volume. Increase of intrathoracic pressure during positive pressure ventilation might partially influence the blood volume change. Our data suggest that isoflurane and sevoflurane do not greatly affect the circulating blood volume under control ventilation. PMID- 1433874 TI - [Effects of sevoflurane on intracranial pressure and formation and absorption of cerebrospinal fluid in cats]. AB - The effects of sevoflurane on intracranial pressure (ICP) and the formation and absorption of cerebrospinal fluid (CSF) were examined in cats. Changes in ICP and superior sagittal sinus pressure (SSSP) were studied for 180 minutes during anesthesia with 1MAC sevoflurane (2.6%, inspired) and 50% N2O in O2. ICP increased significantly immediately after the start of anesthesia. The level remained for the subsequent 120 minutes, but increased significantly again 140 minutes after the start of anesthesia. There was no change in SSSP. The rate of CSF formation (Vf) was examined using the open ventriculocisternal perfusion method during anesthesia for 180 minutes with 1MAC sevoflurane or 1MAC enflurane (2.4%, inspired) and 50% N2O in O2. During sevoflurane administration, Vf decreased significantly 30 minutes after the start of anesthesia. In contrast, during enflurane administration, Vf increased significantly 10 minutes after the start of anesthesia. Finally, Vf and the rate of CSF absorption (Va) were measured under 1MAC sevoflurane or 1MAC enflurane and 50% N2O in O2 anesthesia, or under 50% N2O in O2 anesthesia. They were compared with ICP level. Vf decreased significantly when ICP level increased in all groups. The increase in Va when ICP level increased, was greater in the N2O group than in those anesthetized with sevoflurane or enflurane. The delayed increase of ICP under sevoflurane may have resulted in part from the cranial accumulation of CSF due to increased resistance to CSF absorption. PMID- 1433875 TI - [Effects of sevoflurane on regional myocardial oxygen balance in the canine heart with coronary artery stenosis]. AB - The effects of increasing inspired sevoflurane (Sev) concentrations (0.5, 1.0, 1.5, 2.0 MAC) on regional myocardial oxygen balance and metabolism were studied in 10 open-chest dogs with coronary artery stenosis. Regional myocardial oxygen balance was assessed by continuous recording of subendocardial and subepicardial oxygen tensions. After the basal measurement, the left circumflex coronary artery blood flow (CBFLCX) was reduced by 20% with a screw flow regulator. The institution of stenosis caused a slight but significant decline in subendocardial oxygen tension. Otherwise, there were no significant differences between basal values and those after the stenosis. During the subsequent inhalation of Sev at 0.5, 1.0 and 1.5 MAC, endocardial oxygen tension was maintained at the level of control value. Sev 2.0 MAC caused a severe reduction in systemic arterial pressure and resulted in a marked and significant decline of endocardial oxygen tension compared with control value. On the other hand, subepicardial oxygen tension remained unchanged during each Sev inhalation. The ratio of epicardial/endocardial oxygen tension did not show a significant decline with increasing Sev concentration. It seems that Sev may not possess sufficient potency to cause myocardial ischemia by redistribution of coronary blood flow. PMID- 1433876 TI - [The effects of preanesthetic oral clonidine upon heart rate response to intravenous atropine in patients during general anesthesia]. AB - In awake subjects the positive chronotropic effect of intravenously administered atropine 10 micrograms.kg-1 has been demonstrated to be blunted by preanesthetic medication of oral clonidine 5 micrograms.kg-1. The aim of the present study is to investigate whether general anesthesia could alter the clonidine-induced attenuation of positive chronotropic effect by atropine. Thirty-two patients were randomly assigned to one of the two groups; patients of the clonidine group received oral clonidine 5 micrograms.kg-1 (n = 12), whereas those of the control group received no clonidine. General anesthesia was induced with intravenous thiamylal 4-5 mg.kg-1, and was maintained with enflurane and nitrous oxide in oxygen after endotracheal intubation. Following the stable circulatory period of 10 min, hemodynamic measurements were made at 1 min intervals for 10 min after atropine 10 micrograms.kg-1 was administered intravenously as a bolus in both groups. A significant attenuation in heart rate response to intravenous atropine 10 micrograms.kg-1 was observed in patients receiving clonidine 5 micrograms.kg 1, as compared with that in the control group (P less than 0.01); maximal increases in heart rate were 15 +/- 8 and 22 +/- 6 beats.min-1 (mean +/- SD) in the clonidine and control groups, respectively. It is concluded that clonidine 5 micrograms.kg-1 blunts the heart rate response to intravenous atropine 10 micrograms.kg-1 in patients anesthetized with enflurane and nitrous oxide in oxygen. PMID- 1433877 TI - [Changes in plasma LDH-isozyme in rats during hypoxia and its recovery stage]. AB - Rats were placed in an air-tight glass dome connected to a spirometer, into which nitrogen gas was introduced gradually, to achieve oxygen concentration of about 10%. The animals gradually exhibited dyspnea, and became apneic after about 30 min. Most of the rats in this stage died after the sampling. A different group of rats were returned to the room air from the apneic stage with hypoxia, and were used for the study on the recovery stage. Blood gas analysis revealed severe acidosis and hypoxemia during the apneic stage, while PO2, O2 CT, and O2SAT increased rapidly and significantly during the recovery stage. pH was unchanged between the apneic and recovery stages. During the apneic stage, plasma LDH zymogram was similar to that of the liver taken as the control. However, after returning from hypoxia, the LDH-isozyme patterns quickly approached that of the heart muscle with increasing LDH1 and LDH2. During hypoxia, the changes of arterial oxygen content with alteration of blood flow in the organs, brought direct effects upon the blood isozyme patterns. PMID- 1433878 TI - [Effect of M1 blocker or H2 blocker on gastric secretion during anesthesia and surgery]. AB - Effect of pirenzepine, famotidine or a combination of both agents on gastric secretion during anesthesia and surgery was evaluated in 42 surgical patients ranged in age from 17 y to 70 y. They underwent orthopedic, ophthalmic, ENT, plastic, oral or non-abdominal surgery under either neuroleptanesthesia or enflurane anesthesia. They received either pirenzepine 10 mg, famotidine 20 mg or the combination of both agents intravenously just before the induction of anesthesia. Volume and acidity of gastric juice were measured during 3 hours after the administration of these agents. A continued decrease in volume and acidity of gastric juice was observed 3 hrs after the administration of the agents both in the pirenzepine group and in the famotidine group. Efficacy of the combination of pirenzepine and famotidine on gastric secretion tended to be more prominent than that of either pirenzepine or famotidine alone. PMID- 1433879 TI - [Neuromuscular blocking effect of ORG9426, a new non-depolarizing muscle relaxant, and its recovery with various antagonists in vitro]. AB - We evaluated the neuromuscular blocking effect of ORG9426, a new non-depolarizing muscle relaxant, and its recovery by means of washout or by antagonists in vitro, using phrenic nerve-hemidiaphragm preparations of rats. IC50 and IC90 of ORG9426 in single twitch were 10.62 +/- 0.58 microM and 15.75 +/- 0.95 microM; and those in train of four ratio were 9.04 +/- 0.38 microM and 11.87 +/- 0.42 microM, respectively. The potency of ORG9426 in vitro was compared with those of other non-depolarizing muscle relaxants. The order of potency among the non depolarizing muscle relaxants was the following: d-tubocurarine greater than pipecuronium greater than pancuronium greater than vecuronium greater than ORG9426. There was no difference between ORG9426 and vecuronium in the recovery from block with washout, neostigmine, 4-aminopyridine, 3, 4-diaminopyridine, and edrophonium. In conclusion, the potency of ORG9426 is relatively low, and it can be easily antagonized by anti-cholinesterases and aminopyridines. PMID- 1433880 TI - [Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--15. Application for cardiac anesthesia]. AB - Total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK) was administered to 36 cardiac patients who underwent mostly coronary artery bypass graft or heart valve replacement. The induction and maintenance of anesthesia using this technique were almost satisfactory with little decrease in systolic blood pressure (SBP), although six patients among the early 21 patients developed hypotension below 90 mmHg (SBP) during the induction, and required vasopressors. Half of the patients had hypertensive episode of above 180 mmHg (SBP), from the start of operation to onset of cardiopulmonary bypass, which was safely and effectively overcome by a small dose of antihypertensive agents. Total intravenous anesthesia with DFK was accompanied with much more hypertensive episodes compared to anesthesia with moderate dose fentanyl (30 micrograms.kg-1) combined with enflurane. However, the incidence of cardiovascular complications following anesthesia was not statistically different between the two anesthesia groups. In addition, most of the patients with DFK showed a rapid awaking time with relatively good postoperative cardiovascular stability. These findings suggest that total intravenous anesthesia with DFK is accompanied with minimal hemodynamic changes during and after open heart surgery. PMID- 1433881 TI - [The effect of preoperative oral administration of ranitidine on pH and volume of gastric juice]. AB - The effect of ranitidine, administrated 2 or 4 hours prior to induction of anesthesia, on volume and pH of gastric juice was investigated in patients undergoing elective surgery. Three-hundred mg of ranitidine was administrated orally in 54 patients 2 hours prior to anesthesia and in 50 patients 4 hours prior to anesthesia. The volume and pH of gastric juice were measured immediately after induction of anesthesia. In more than 90% of patients of both groups, volume of gastric juice was smaller than 25 ml and its pH was more than 2.5. Ranitidine 450 mg was administrated orally in 7 patients, and its plasma concentration was measured 2, 4 and 6 hours after administration. In one patient, volume of gastric juice was larger than 25 ml and its pH was less than 2.5. Ranitidine concentration in this patient was below the effective level 2 hours after administration and it was above the level after 4 hours. We concluded that oral administration of ranitidine 300 mg, 4 hours preoperatively, could be more effective to prevent aspiration pneumonitis than when it is given 2 hours preoperatively. PMID- 1433882 TI - [A case of coronary spasm during the operation for lung cancer]. AB - We reported a case of coronary spasm during the operation for lung cancer. A 72 year-old man underwent left upper lobectomy for lung cancer under general anesthesia with the aid of thoracic epidural anesthesia. Preoperative examinations did not reveal any clinical problems in the past. Hypotension and premature ventricular beats were observed for several times during operation due to the compression of the heart and left pulmonary artery by the surgeon's hands in stopping brisk bleeding. After this event, ST-segment of ECG was elevated abruptly. Intravenous administration of nitroglycerin was effective to relieve the coronary spasm in this case. Possible triggering factors were mechanical injury of the coronary artery due to compression of the heart, vagal stimuli under thoracic epidural anesthesia and alpha-stimulating drugs to treat hypotension. The importance of preoperative evaluation of coronary lesions, perioperative treatments with nitrates and calcium-channel blockers, and avoidance of intraoperative triggering factors are emphasized to prevent the coronary spasm. PMID- 1433883 TI - [Compression of the graft during the corrective surgery for scoliosis in a patient who has undergone a Rastelli's operation: a case study]. AB - A 14 year-old male who had undergone Rastelli's operation for the tetralogy of Fallot had general anesthesia for the corrective spinal instrumentation and posterior fusion. The patient also suffered from the complication of Klippel-Feil syndrome. During the operation, right ventricular pressure gradually increased from 34 mmHg to 60 mmHg and systolic blood pressure decreased from 110 mg to 80 mmHg when the maneuver to correct spinal deformity was done. The hemodynamics returned to its former level after the maneuver was resumed. This change was presumably attributed to the fact that the external conduit was compressed by the sternum and vertebral bodies. In order to prevent this hazardous incidence, it is crucial to understand both the three-dimensional configuration of the thoracic structure and the influence of spinal correction on it. In the prone positioned patients with scoliosis, especially lordoscoliosis, compression or dysfunction of the artificial valve might occur and we have to be aware of the possibility of the compression during general anesthesia and after corrective surgery. PMID- 1433884 TI - [A case of tracheobronchopathia osteoplastica discovered after difficulty in intubation]. AB - A 77-year-old man was scheduled for Love's method to correct lumbar disc herniation. He had fracture of maxilla and mandibula during World War II. Physical examination and laboratory data revealed no abnormalities. Anesthesia was induced with oxygen, nitrous oxide and halothane. Following administration of succinylcholine, an attempt was made to insert a tracheal tube (from 8.5mm to 5.5mm), but the tubes were met with an obstruction. The operation was cancelled because tumor-like nodules were seen in the trachea. Diagnosis of tracheobronchopathia osteoplastica was made afterwards following biopsy. The patient with this disease has a good prognosis. Artificial ventilation can be performed safely by choosing an appropriate method for airway maintenance. PMID- 1433885 TI - [A case of pulmonary embolism after abdominal surgery]. AB - A 67-yr-old man who suffered from pulmonary embolism following abdominal surgery was reported. The patient received left hemicolectomy and cholecystectomy for cancer of descending colon and cholecystolithiasis, respectively. Anesthesia was maintained with enflurane 0.6-1.0% and pancuronium combined with epidural analgesia. The anesthetic course was uneventful. But after leaving operating room the patient showed severe hypoxemia without abnormal shadow on chest X-P and other abnormal laboratory values. The cause of hypoxemia was unclear, but on the fourth postoperative day pulmonary scintigrams revealed pulmonary embolism. Then 12000 units.day-1 of heparin infusion was started. After 10 days of anticoagulant therapy, the hypoxemia improved and he was discharged on 28th postoperative day. Although pulmonary embolism is a rare disorder, we have to take it into consideration as one of the causes of postoperative hypoxemia. PMID- 1433886 TI - [Two cases of diffuse pulmonary lymphangiomyomatosis]. AB - We cared 2 patients with diffuse pulmonary lymphangiomyomatosis (LAM) through the perioperative period. LAM is a disease of uncertain origin and poor prognosis because of respiratory failure. Therefore, it is important to provide not only a good anesthetic care but also a good preoperative respiratory care. In the first case (a 35-yr-old woman), an open lung biopsy was performed after dyspnea and sputum had disappeared with preoperative medications of a bronchodilator and some antibiotics. In the second case (a 35-yr-old woman), oophorectomy was performed after FEV1.0% had remarkably increased with preoperative medication of a bronchodilator. Both patients did well through the perioperative period without any trouble or complications, such as pneumonia or severe hypoxemia, presumably owing to our perioperative management system. PMID- 1433887 TI - [Intrathecal morphine for postoperative pain relief after transvaginal hysterectomy]. AB - We studied the effect of a low-dose intrathecal morphine (0.1 or 0.2 mg) in postoperative pain relief and the incidence of side effects. Two hundred and fifteen patients scheduled for transvaginal hysterectomy were divided into 3 groups according to intrathecal morphine doses: M1 (morphine 0.1 mg N = 75), M2 (morphine 0.2 mg N = 69) and C (control N = 71). A standard mid-line lumbar puncture was performed using a 25-gauze needle in the L3/4 interspace. Preservative-free morphine hydrochloride mixed in hyperbaric tetracaine solution was administered intrathecally. Pain relief was significantly greater for the first 24 hrs in groups M1 and M2 compared with group C. Respiratory depression was not seen in any groups. The incidence of vomiting was about 40% in all groups. We conclude that intrathecal morphine 0.1-0.2 mg is useful for pain relief after transvaginal hysterectomy and accompanies no major side effects. PMID- 1433888 TI - [Clinical evaluation of sulbactam/cefoperazone for severe infections associated with hematological disorders]. AB - The combination therapy of sulbactam/cefoperazone (SBT/CPZ) and piperacillin (PIPC) was evaluated in 49 patients with severe infections associated with hematological disorders. Clinical responses in 43 evaluable patients out of the 49 patients were excellent in 12, good in 18, thus, overall efficacy rate was 69.8% (excellent plus good). Efficacy rates of this combination therapy were 60% (3/5) for sepsis, 75% (21/28) for suspected sepsis, and 50% (4/8) for pneumonia. The efficacy rate was 71.4% (10/14) in patients with neutrophil counts less than 200/microliters; this combination therapy was highly effective even in the neutropenic patients. Transient increases in hepatic function test values were observed in 2 patients, but no other side effects were observed during the combination therapy. From these observations it appears that the combination therapy of SBT/CPZ and PIPC is a very useful empiric therapy for severe infections associated with hematological diseases. PMID- 1433889 TI - [A randomized controlled study on imipenem/cilastatin sodium in comparison to aztreonam + lincomycin in treating severe infections in patients with malignant tumors or hematological diseases]. AB - A randomized controlled study was conducted to compare effects of imipenem (IPM) (1.0-1.5 g/day) with those of aztreonam (AZT) (4 g/day) +lincomycin (LCM) (1,200 2,400 mg/day) in patients with malignant tumors or hematological diseases and severe infections. A total of 95 patients entered the study between October 1989 and March 1991. Forty-seven patients were treated with IPM and the remaining 48 patients were given AZT+LCM. No statistically significant differences existed in age, sex or underlying diseases between the 2 groups. Overall, the clinical cure rate of the IPM group was 53%; This was significantly higher than the 31% cure rate obtained in the AZT+LCM group (P less than 0.05). The difference was significant in patients whose granulocyte counts were less than 1,000/microliters, but not in those whose granulocyte counts were 1,000/microliters or higher. Side effects were observed in 5 patients given IPM and one given AZT+LCM. In conclusion, no significant differences appeared to exist regarding clinical efficacy and safety between the 2 treatment regimens. PMID- 1433890 TI - [Clinical evaluation of imipenem/cilastatin sodium against infections in compromised children (malignancy, hematological disease, collagen disease)]. AB - Eighteen immuno-compromised children (malignancies, hematological diseases, collagen diseases) with neutropenia and infections were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and the safety of the drug were evaluated. 1. Responses to IPM/CS were excellent in 13 patients, good in 1, and fair in 4. None of the patients displayed a poor response to the treatment thus the efficacy rate was 77.8%. 2. Of 5 patients with sepsis, 4 had excellent or good responses. IPM/CS was effective against sepsis caused by Enterococcus faecalis and Pseudomonas aeruginosa. 3. In patients with severe neutropenia (WBC less than 100/mm3), the efficacy rate was 70%. 4. As for side effects, elevations of GOT and GPT were observed in 1 patient with liver cirrhosis. These results indicate that IPM/CS is safe and effective in immuno-compromised children with neutropenia and infections. PMID- 1433891 TI - [Clinical studies on imipenem/cilastatin sodium in the early therapy of preterm premature rupture of the membrane or threatened abortion and premature delivery]. AB - The efficacy and safety of early therapy with imipenem/cilastatin sodium (IPM/CS) were studied in patients who had chorioamnionitis with preterm PROM or threatened abortion and premature delivery. The following results were obtained. 1. The clinical efficacy of IPM/CS administered by intravenous drip infusion at daily dosages of 1 to 2 g as concurrent treatment with antiuteronics (ritodrine hydrochloride or terbutaline sulfate) was studied in patients with threatened abortion and premature delivery in the 11th to 34th week of pregnancy (n = 9), or premature PROM in the 23rd to 36th week (n = 9). 2. Response to IPM/CS were good in all of the patients with threatened abortion and premature delivery. Latent periods were prolonged for more than 7 days in 44.4% (4/9) of the patients with preterm PROM. 3. Changes in elastase appeared to be significant as those in CRP for inflammatory markers. 4. These findings combined with our previous results indicate that treatment of preterm PROM before the 32nd of pregnancy prolongs the latent period. PMID- 1433892 TI - [Clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology]. AB - The efficacy and safety of imipenem/cilastatin sodium (IPM/CS) were studied in patients with obstetric and gynecologic infections and in those given the drug as prophylaxis against postoperative infections. The following results were obtained: 1. Efficacy rates were 96.0% (48/50) in patients with obstetric and gynecologic infections and 100% (28/28) in those with urinary tract or other infections. The overall efficacy rate was 97.4% (76/78). Bacteriologically, 30 organisms were isolated from 28 patients. The eradication rate was 95.2% (20/21) and the efficacy rate was 96.4% (27/28). 2. Changes in blood elastase before and after treatment were compared with those in CRP, WBC, and ESR in the patients with obstetric and gynecologic infections. The changes in elastase were similar to those in CRP. 3. The efficacy rate was 98.0% (48/49) in the patients given prophylaxis against postoperative obstetric and gynecologic infections. 4. An adverse reaction was observed in only one patient (diarrhea), and abnormal laboratory findings were noted in 2 patients (elevation of GOT and GPT). These results indicate that IPM/CS is very useful for the treatment of obstetric and gynecologic infections. PMID- 1433893 TI - [A clinical study of transfer of cefminox and piperacillin into pulmonary tissue]. AB - Serum concentrations of cefminox (CMNX) and piperacillin (PIPC) and their transfer into pulmonary tissue during surgery were serially studied following 1 hour intravenous instillation of 1 g of CMNX or PIPC immediately before thoracotomy, and the following results were obtained. Maximum serum concentrations of CMNX and PIPC were observed 1 hour after the commencement of administration, and their levels gradually decreased thereafter. The mean peak level of CMNX was 72.21 micrograms/ml, and T 1/2 was 1.62 hours. The mean peak level of PIPC was 43.26 micrograms/ml, and T 1/2 was 1.54 hours. In the pulmonary tissue, mean concentrations of CMNX in the normal pulmonary (alveolar) tissue were 28.80, 26.50 and 17.80 micrograms/g at 2.5, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 19.6, 18.40 and 20.53 micrograms/g, respectively. The mean concentrations of PIPC in the normal pulmonary (alveolar) tissue were 18.97, 7.34 and 5.0 micrograms/g at 2, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 7.2, 9.20 and less than 0.2 micrograms/g, respectively. PIPC also showed favorable transfer into the hilar lymph node tissue and obstructive pneumonitic lesions. The transfer of both drugs into pulmonary tissue suggests that both drugs are useful for the treatment of respiratory infectious diseases and the prevention of postoperative infections. PMID- 1433894 TI - [Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders]. AB - The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders. PMID- 1433895 TI - [Clinical evaluation of flucytosine in patients with urinary fungal infections]. AB - The clinical effectiveness of flucytosine (5-FC) was evaluated in 52 patients with urinary fungal infections which were diagnosed because of the presence of both funguria (greater than or equal to 10(4) cfu/ml) and pyuria (greater than or equal to 5 WBC/hpf). The patients received oral daily doses of 5-FC ranging 20 to 150 mg/kg, with a mean treatment duration of 11 days. The 57 fungus strains isolated from urine specimens consisted of 51 Candida spp. including 28 Candida albicans, 10 Candida glabrata, 4 Candida tropicalis and 6 Trichosporon beigelii. Forty-seven (92.2%) and 4 (66.7%) of the 51 Candida spp. and 6 T. beigelii strains isolated were eradicated by the treatment, respectively, giving an overall eradication rate of 89.5%. Clinical responses in 32 patients, from whom only fungi were submitted, were excellent in 5, moderate in 22, and poor in 5, thus the overall efficacy rate was 84.4%, based on the criteria of Japanese UTI Committee. Of the 18 strains of Candida spp. tested, 5-FC showed 0.20 micrograms/ml or less of the minimum inhibitory concentrations (MICs) against 16 strains and higher than 100 micrograms/ml against the remaining 2 strains. The MICs of the 5 T. beigelii strains tested were between 3.12 and 6.25 micrograms/ml. As adverse reactions, only 2 patients (3.8%) experienced diarrhea but did not require treatment cessation. These results suggest that flucytosine is an effective drug for urinary fungal infections. PMID- 1433896 TI - Comparisons of the bacterial flora in genital regions at non-pregnancy. AB - In the development of infectious diseases at non-pregnancy and at pregnancy, correlations between bacterial flora in the vagina and portio vaginalis and the ascending infections of those bacteria have recently been discussed. To clarify the cause of those infectious diseases, we studied the localization of microorganisms in genital regions. Patients undergone abdominal total hysterectomy (n = 172) were employed as subjects, and microorganisms isolated from 4 genital regions were studied. In addition, the preventive effect of cefmetazole (CMZ) against postoperative infections was analyzed in 479 cases including the hysterectomy cases mentioned above. The results obtained are summarized as follows: 1. The isolation rate of microorganisms at non-pregnancy, from subjects of 30 to 69 years old, was 65.6% (82/125) in the vagina and portio vaginalis, 52.1% (25/48) in the cervical mucus, 7.3% (9/124) in the uterine cavity and 0% (0/47) in the ovarian surface. 2. Numbers of microorganisms isolated in each region were 99 strains in the vagina and portio vaginalis, 28 in the cervical mucus, 10 in the uterine cavity and none in the ovarian surface. Isolation of aerobic Gram-positive bacteria (60-89.3%) and anaerobic Gram positive bacteria (7.1-30%) were varied in each region. Lactobacillus spp. (38 strains), Staphylococcus epidermidis (20 strains) and Propionibacterium acnes (10 strains) were isolated from vagina and portio vaginalis, and Lactobacillus spp. (17 strains) were the most often isolated bacteria from the cervical mucus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1433897 TI - [A new oral cephem, cefdinir: its structure-activity relationships and biological profile]. AB - This article reviews structure-activity relationships and biological properties of a new oral cephem, cefidinir (CFDN). It also describes a hypothesis concerning the absorption mechanism from the intestine. Antibacterial activities and the oral absorption efficiencies were studied with regard to 3-vinyl cephalosporins with various 7-acyl side chains. From the study, 2-(2-aminothiazol-4-yl)-2 hydroxyiminoacetyl group was selected and various 3-substituents were screened. As a result, it was found that the vinyl compound, CFDN, showed excellent antibacterial activity and good oral absorption in rats. In vitro and in vivo antibacterial activities, the affinity for PBPs and the stability to beta lactamases revealed that CFDN had well balanced antimicrobial activities against Gram-positive and Gram-negative bacteria and good biological properties. The pharmacokinetics of CFDN in healthy volunteers showed that serum concentration and half life were good enough to make CFDN an effective therapeutic agent. The mechanism of intestinal absorption of CFDN and related oral cephems are discussed and a hypothesis for molecular recognition by the carrier protein in the intestine is proposed. PMID- 1433898 TI - [Study on the pharmacokinetics of cefepime (I)]. AB - The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), were studied in rats upon both single and repeated intravenous administration. 1. Blood level of radioactivity was 59.27 micrograms eq./ml at 5 minutes after single intravenous administration at a dose of 20 mg/kg, and declined biexponentially thereafter. The values of AUC and T 1/2 were 70.1 micrograms eq..hr/ml and 38.0 hours, respectively. 2. Blood level of radioactivity was 59.41 micrograms eq./ml at 5 minutes after administration on the 7th day of repeated intravenous administration at a daily dose of 20 mg/kg, and declined more slowly as compared to the case of single administration. The values of AUC and T 1/2 after repeated administration were 159.7 micrograms eq..hr/ml and 44.5 hours, respectively. 3. Urinary and fecal excretion rates after single administration were 93.3% and 3.3%, respectively. 4. Urinary and fecal excretion rates were almost constant throughout the repeated administration; 88.4-90.7% and 2.3-3.7%, respectively. 5. 14C-CFPM distributed rapidly to the whole body except to the central nervous system. Although the radioactivity was removed rapidly from tissues, high levels of radioactivity remained in the kidney and the spleen as compared to other tissues. 6. Tissue concentrations of radioactivity at 5 minutes after the final dose of repeated administration were about the same as those after single administration but they declined more slowly than those after single administration. High levels of radioactivity were found in the kidney and the spleen as were found upon single administration. The ratios of these levels between repeated and single dosing were 4.3 and 2.6 for kidney and spleen, respectively. 7. Data obtained with autoradiograms of the whole body were consistent with measured tissue distribution obtained in both cases of single and repeated administration. PMID- 1433899 TI - [Study on the pharmacokinetics of cefepime (II)]. AB - The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), was studied in dogs after single intravenous administration at a dose of 20 mg/kg. Protein binding was also investigated both in vitro and in vivo. 1. Blood level of radioactivity was 83.53 microns eq./ml at 5 minutes after single intravenous administration and declined biexponentially thereafter. The values of AUC and T1/2 were 229 microns eq.(.)hr/ml and 90 hours, respectively. 2. Urinary and fecal excretion rates were 95.1% and 2.7%, respectively. 3. The in vitro protein binding at 1 to 100 microns/ml of drug concentration was 7.9 to 12.7% in rat, 12.4 to 18.6% in human, and 12.5 to 14.5% in dog. In vivo protein binding, which increased with time after administration, was 10.8 to 92.9% in rat and 17.5 to 64.9% in dog at 5 minutes to 6 hours. PMID- 1433900 TI - Cross-resistance of clinical isolates of methicillin-resistant Staphylococcus aureus to aminoglycosides and fluoroquinolones. AB - Susceptibilities of 117 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to aminoglycosides and fluoroquinolones were investigated during 1987 and 1990. Gentamicin, tobramycin, sisomicin, micronomicin, and astromicin showed the bimodal antimicrobial activity pattern against MRSA, revealing cross resistance to these antibiotics. However, amikacin, netilmicin, isepamicin and arbekacin (ABK) exhibited the monomodal antimicrobial activity pattern, suggesting the presence of less resistant strains. All 117 MRSA strains were susceptible to ABK with MICs less than 3 micrograms/ml. MRSA also showed the bimodal antimicrobial susceptibility pattern to fluoroquinolones such as ofloxacin (OFLX), ciprofloxacin (CPFX) and tosufloxacin (TFLX). Frequencies of TFLX susceptible MRSA isolates decreased progressively from 1987 to 1989 when this drug was not even in general clinical use. The cross-resistance of MRSA between TFLX and OFLX or CPFX persisted. Cross-resistance between aminoglycosides and fluoroquinolones, however, was less frequently observed. PMID- 1433901 TI - [Combined effects of arbekacin with other antibiotics against methicillin resistant Staphylococcus aureus. I. The combined effect of arbekacin with fosfomycin or clavulanic acid/ticarcillin]. AB - As arbekacin (ABK) has a highly potent antibacterial activity against methicillin resistant Staphylococcus aureus (MRSA), its combined effects with fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) against MRSA were examined. The obtained results are summarized as follows. 1. Against MRSA either combination, FOM+ABK or CVA/TIPC+ABK showed a strong antibacterial effect at the MIC or the sub MIC of ABK in the blood expected from clinical observations. The MIC of ABK by the combination use seemed to be equivalent to the MBC value. 2. Effective concentrations of antibiotics in these combinations appeared to be strongly dependent on the effective concentration of ABK and less dependent on that of FOM or CVA/TIPC. Therefore, the antibacterial activity of a combination seems to mostly depend on the antibacterial activity and the concentration of ABK. 3. As FOM and CVA/TIPC have antibacterial activities against Pseudomonas aeruginosa, combinations of ABK with these antibiotics are likely to be effective against double infection with P. aeruginosa in MRSA infected patients. PMID- 1433902 TI - [Combined effects of arbekacin with other antibiotics against methicillin resistant Staphylococcus aureus. II. The combined effect of arbekacin with imipenem or cefminox]. AB - Combined antibacterial effects of imipenem (IPM)+arbekacin (ABK) and cefminox (CMNX)+ABK against methicillin-resistant Staphylococcus aureus (MRSA) were examined and the obtained results are summarized below. 1. Either combination, IPM+ABK or CMNX+ABK, showed a strong antibacterial effect against MRSA when blood concentration of ABK were sustained at MIC as could be expected in clinical situations. While at sub MICs of ABK the antibacterial effect of these combination was slightly less than those of the previously reported combinations of ABK and other antibiotics. 2. Antibacterial effects of the combinations against MRSA were strongly dependent on the concentration of ABK and less dependent on the concentration of IPM or CMNX. As were observed in the previously tested combinations of ABK with other antibiotics, the antibacterial effect of the combination appeared to be highly dependent on the antibacterial activity and the concentration of ABK. 3. As IPM has potent antibacterial activities against Gram-negative bacteria (GNB) including Pseudomonas aeruginosa while CMNX has potent antibacterial activities against GNB except P. aeruginosa, it is likely that the combinations of IPM+ABK or CMNX+ABK are useful for treatment of infections with MRSA together with GNB. PMID- 1433903 TI - [Antimicrobial activities of major oral antibacterial agents against clinically isolated microbial strains from inpatients]. AB - Antimicrobial activities were examined for major antibacterial agents against clinically isolated microbial strains which were isolated and identified from materials collected from inpatients with various infections in 1988, 1989 and 1990, and the following conclusions were obtained. 1. Among strains isolated each year, methicillin-resistant Staphylococcus aureus (MRSA) were found frequently. 2. CEPs-resistant Escherichia coli strains were observed among strains isolated each year. 3. Increasing tendencies in resistances of Citrobacter freundii, Enterobacter spp., Serratia marcescens to cephems and new quinolones were observed. 4. Increasing tendencies in resistances of Proteus vulgaris to ceftazidime (CAZ) and new quinolones appeared to exist. 5. Among strains isolated each year, resistances of Pseudomonas aeruginosa to CAZ and quinolones were observed in high rates, but also their resistances to imipenem appeared to increase. 6. Many of recently increasing multiple resistant bacteria seem to have different sites of drug action and/or to have non-hydrolytic modes of resistance. PMID- 1433904 TI - [Antimicrobial activities of major oral antibacterial agents against clinically isolated microbial strains from outpatients with respiratory tract infection]. AB - Minimum inhibitory concentrations (MICs) were determined for major oral antibacterial agents for clinically isolated microbial strains from materials collected from outpatients with respiratory tract infections in 1988, 1989 and 1990, and the following conclusions were obtained. 1. Methicillin-resistant Staphylococcus aureus (MRSA) appeared to be responsible for community-acquired respiratory tract infections, but there also was a tendency showing that MRSA increased year by year. 2. A tendency was observed indicating that benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) increased year by year. 3. Beta-lactamase-producing strains of Haemophilus influenzae were observed in a certain ratio, and also those of Branhamella catarrhalis were found in high ratios. 4. A tendency of increasing resistance of Klebsiella pneumoniae to new quinolones was observed. 5. It is of a great importance to evaluate methods of selecting primary choice antibiotic agents since increasing numbers of new oral antibacterial agents are becoming rapidly available. PMID- 1433905 TI - [Antibacterial activities of sisomicin against fresh clinical isolates]. AB - To investigate antibacterial activities of sisomicin (SISO), MICs of SISO as well as other aminoglycosides (AGs) were determined against many clinical isolates which were obtained in 1991. Results are summarized below: 1. No SISO-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Proteus mirabilis and Morganella morganii. 2. In comparison with the results of our previous study against isolates obtained in 1986, the rate of methicillin resistant Staphylococcus aureus (MRSA) was higher, and SISO-resistant strains were observed at a high rate among the MRSA. Also, SISO-resistant strains of Serratia marcescens increased. However, the rate of SISO-resistant strains of Pseudomonas aeruginosa decreased, and among Citrobacter freundii, Enterobacter cloacae and Proteus vulgaris, SISO-resistant strains did not increase over the years. 3. MICs of SISO against Providencia rettgeri and Providencia stuartii were high, suggesting that antibacterial activities of SISO was weak against genus Providencia. 4. For comparison, according to MICs of ofloxacin and imipenem, new quinolone-resistant strains were observed at a high rate among various organisms, and carbapenem-resistant strains were observed at a high rate among S. marcescens and P. aeruginosa. 5. SISO is still one of the useful AGs in the 1990's since it maintains its strong antibacterial activities against most clinical isolates obtained in recent years and its potential as a combination drug with beta lactams is being reported. PMID- 1433906 TI - [Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). I. Susceptibility distribution]. AB - Isolation frequencies and sensitivities to antibacterial and antibiotic agents were investigated on 801 bacterial strains isolated from patients with urinary tract infections in 9 hospitals during the period of June to November 1988. Of the above total bacterial population, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus spp. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. 1. Enterococcus faecalis: Vancomycin was most active with its MIC90 < or = 0.78 microgram/ml. Ampicillin, piperacillin, ofloxacin (OFLX), ciprofloxacin (CPFX) and imipenem (IPM) were also active. 2. Staphylococcus aureus: Arbekacin and minocycline were most active with their MIC90s 0.39 microgram/ml and 1.56 micrograms/ml, respectively. Among penicillins, dicloxacillin was the most active. Activities of cephems were considerably lower. 3. E. coli: Most of the agents were tested active. Particularly the second and third generation cephems were active in a range of < or = 0.10-0.20 microgram/ml. Carumonam (CRMN), IPM, OFLX and CPFX were also active with MIC90s < or = 0.10 microgram/ml. 4. Klebsiella pneumoniae CRMN and IPM were highly active. Penicillins generally showed lower activities. Cephems and new quinolones had high activities with their MIC90s in a range of 0.39-0.78 microgram/ml. 5. Proteus mirabilis: The third generation cephems were active with their MIC90s in a range of < or = 0.10-0.20 microgram/ml. CRMN, OFLX and CPFX were also active with their MIC90s < or = 0.10 microgram/ml, 0.39 microgram/ml and 0.20 microgram/ml, respectively. 6. Pseudomonas aeruginosa: IPM and tobramycin were active with their MIC90s 1.56 micrograms/ml and 3.13 micrograms/ml, respectively. CRMN and new quinolones showed MIC80s of 25-100 micrograms/ml. Most of penicillins and cephems were not active. 7. Other Gram negative rods: Against Citrobacter freundii, Enterobacter cloacae and Serratia marcescens, IPM, CPFX and OFLX were active. Penicillins and cephems were not so active. CRMN was active against S. marcescens with its MIC80 at 6.25 micrograms/ml. PMID- 1433908 TI - [Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). III. Secular changes in susceptibility]. AB - Sensitivities to various antibacterial and antibiotic agents of strains of Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia marcescens and Pseudomonas aeruginosa isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June to November 1988 were compared with those in the same period of previous year according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. No remarkable changes were found in sensitivities of E. coli, Proteus spp., Citrobacter spp. and S. marcescens. The sensitivity of Klebsiella spp. to cephems decreased in complicated UTI without indwelling catheter and increased in complicated UTI with indwelling catheter. The sensitivity of Enterobacter spp. to third generation cephems decreased in complicated UTI with indwelling catheter. Sensitivities of P. aeruginosa to aspoxicillin and cefsulodin increased. The number of resistant strains to new quinolones increased slightly. PMID- 1433907 TI - [Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). II. Background of patients]. AB - Clinical background was investigated on 916 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period from June to November, 1988. 1. Distribution of sexes, ages and infections: Among males, fifties and older were most frequent and most of them had complicated UTIs. Among females, most cases among twenties or thirties were uncomplicated UTIs. Forties and older cases were most frequent and complicated UTIs were more frequent among them than among patients in twenties and thirties. 2. Distribution of sexes, ages and pathogens isolated from UTIs: In males, Pseudomonas spp. and Enterococcus spp. were frequently isolated. In contrast, in females, Escherichia coli was the most frequent. In thirties, E. coli was not the most frequently isolated bacterium. Frequency of Pseudomonas spp., other non-fermented Gram negative rods and Enterococcus spp. were greater among patients with higher ages. 3. Administration of antibiotics and pathogens isolated from UTIs: (1) Before administration: In uncomplicated UTIs, E. coli accounted for the majority of causative organisms. In complicated UTIs, particularly in those cases with indwelling catheter, Enterococcus spp. and Pseudomonas spp. were rather frequently isolated. (2) After administration: In complicated UTIs, higher number of pathogens were isolated. Pseudomonas spp. and Enterococcus spp. were the most frequent. Distribution of pathogens isolated from complicated UTIs without indwelling catheter was similar to that before antibiotic administration. PMID- 1433909 TI - [Salmonella vaccines and immunity]. PMID- 1433910 TI - [Phosphoenolpyruvate:hexose phosphotransferase systems in Lactobacillus species]. AB - The substrate range of phosphoenolpyruvate:hexose phosphotransferase systems (hexose-PTSs) in Lactobacillus casei subsp. casei LAC3 and L. acidophilus LAC5 was examined. Strain LAC3 demonstrated PTS activities for glucose (Glc), mannose (Man), glucosamine (GcN), 2-deoxyglucose (2DG) and fructose (Fru), while strain LAC5 showed the activities only for Man and Fru. These activities were all constitutive. Growth of both strains was strongly inhibited by 2DG. 2DG-resistant mutants DG329 and DG504 were isolated, respectively, from strains LAC3 and LAC5. Mutant DG329 grown on Glc was defective in all the above-described activities observed with strain LAC3, whereas no defect in PTS activities was found in mutant DG504. Mutant DG329, however, showed some inducible activities for Man and Fru when grown on Man, Fru or Scr. These results strongly suggest that strain LAC3 has inducible PTS(s) specific for Man and/or Fru besides the well-known, broadly specific, constitutive Man-PTS, and also that strain LAC5 lacks the Man PTS, but has other constitutive PTS(s) specific for Man and/or Fru. L. fermentum LAC12 had the Man-PTS as reported previously (Nagasaki et al., 1992), but had no inducible activities like those found in strain LAC3. PMID- 1433911 TI - [Effect of pH on preferential antibacterial-activity of ethylenediaminetetraacetic acid (EDTA)]. AB - Ethylenediaminetetraacetic acid (EDTA), a chelating agent, was examined for the antibacterial activity against 15 species of bacteria by treating with a 10mM solution at pH adjusted to 5.0, 7.0 or 9.0. All bacterial species tested were classified into three groups; tentatively named the pH5 EDTA-sensitive group comprising Vibrio cholerae and Staphylococcus aureus, the pH9 EDTA-sensitive group comprising Escherichia coli and Pseudomonas aeruginosa and the EDTA nonsensitive group comprising Proteus mirabilis. The EDTA-sensitivity grouping may be used as a tool for preferential decontamination of certain bacteria in live edible fishes, although further experiments are needed to characterize more strains and also species of bacteria. PMID- 1433912 TI - [Proteins C,S and C4bp--their structures and functions]. PMID- 1433913 TI - [Genetic analysis of congenital protein C deficiency]. PMID- 1433914 TI - [Acquired protein C or S deficiency--its relationship with physiopathology]. PMID- 1433915 TI - [Protein C as a new therapeutic agent]. PMID- 1433916 TI - [Clinicopathological study of 6 cases of mantle zone lymphoma]. AB - Clinicopathological analyses of 6 cases of mantle zone lymphoma (MZL) were carried out. The median age of the patients was 62 years with a range of 41 to 71 years and the male-to-female ratio was 1:1. Superficial lymph node (LN) swelling was present only in 2 patients. Giant LN swellings of the mesenteric or inguinal regions were present in 4, and bone marrow involvement by lymphoma cells in 5. Serum protein electrophoresis revealed a monoclonal protein of IgM kappa type in 2 patients. One of these also had polyclonal hypergammaglobulinemia. An immunohistochemical study of 6 patients revealed LN-1-(-)+, LN-2+(-)++, sIgM+, sIgD+, CALLA +/-(-)+, DRC-1+(-)++. The immunohistochemical features of the cases were similar to those of small lymphocytic lymphoma or follicular lymphoma. Only 1 patients out of 6 achieved complete remission. Two patients died, one of pneumonia after chemotherapy and the other of cancer. The others were alive 4 to 100 months after the diagnoses. Although giant LN swelling and bone marrow involvement of lymphoma cells which were refractory to treatments were frequently observed, we consider MZL to be a slowly progressive and low-grade type of non Hodgkin's lymphoma. PMID- 1433917 TI - [Interferon therapy of idiopathic thrombocytopenic purpura]. AB - The authors evaluated the efficacy of a daily administration of recombinant human alpha 2a interferon (IFN), given at a dose of 300MU for 12 consecutive days, in patients with steroid-nonresponsive or -dependent idiopathic thrombocytopenic purpura (ITP). Nine patients received courses of IFN therapy. Mean platelet counts rose from 1.39 to 10.9 x 10(4)/microliters and PAIgG decreased from 151.7 to 59.7 ng/10(7) cells. The maximum rise in platelet counts occurred from 10 to 42 days (mean 19.1) after the initiation of IFN. Complete response (CR) was achieved in 3 of 13 courses (23.1%), and partial response (PR) in 8 (61.5%). One CR case continued for longer than 20 months without further treatment, but intermittent IFN therapy was necessary for the other. The increment of the platelet counts was transient in all of the partial responders. No severe side effect requiring interruption of the course of IFN was experienced. Both serum IgG and PAIgG significantly correlated with the increment of platelet counts, therefore the mechanism of IFN on ITP was presumed to be associated with the inhibition of autoantibody production. Daily administration of IFN appears to be an effective and safe treatment protocol for refractory ITP. PMID- 1433918 TI - [Differential diagnosis and course of patients with pure erythrocytosis and spurious polycythemia]. AB - We established the diagnostic criteria of pure erythrocytosis (PE) and spurious polycythemia (SP), and investigated the different points between 4 PE patients and 4 SP patients who had clinical course longer than 5 years from diagnosis. The red cell mass (RCM) was greater in PE patients than in SP patients, but the difference was not significant. However, the actual measurement of RCM was significantly greater in PE than their predicted values (p less than 0.01), and was not significant in SP. Such laboratory data as red cell counts, Hb, Hct, reticulocyte counts, M/E ratio of bone marrow pictures, the positive rate and score of NAP, and bone marrow CFU-E numbers were not significantly different in the two groups, and serum EPO levels in patients with PE were significantly lower than those in patients with SP (p less than 0.01). When in hospital, the Hct levels of patients of both groups decreased linearly. Sustained erythrocytosis was found in two patients with PE and one patient with SP. Vascular complications in patients of both groups have not been observed. There was no essential difference between the two groups. Therefore, it is suggested that PE patients without endogenous erythroid colonies may follow almost the same clinical course as SP patients. PMID- 1433919 TI - [Measurement of busulfan concentration in plasma and spinal fluid from transplant patients pretreated with busulfan and cyclophosphamide]. AB - Busulfan (BU) concentrations in the blood and spinal fluid of 7 patients pretreated with BU for bone marrow transplantation (BMT) were measured using gas chromatography. The data from these periodically obtained samples were used to study the relationship between the BU concentration and complications (e.g. vomiting), indicating that vomiting leads to a lower maximum BU level. The trough level of BU concentration at 6 hours after administration was stable at around 500 ng/ml, not showing little effect of vomiting. The BU concentrations in the spinal fluid were virtually the same as those in plasma collected at the same time and the spinal fluid/plasma ratio of the BU concentration averaged 1.06. No veno-occlusive disease (VOD) was noted. Failure of engraftment occurred in one case of myelofibrosis, however, as the plasma BU concentration in this case was not lower than the others, the graft failure was not considered to be due to the preconditioning regimen including BU. PMID- 1433920 TI - [Cold agglutinin hemolytic anemia complicating mycoplasma pneumonia]. AB - A case of Mycoplasma pneumonia complicated with severe hemolytic anemia, which occurred as a result of a high titer of cold agglutinin is presented. A 49 year old male was admitted because of fever, jaundice and dyspnea. Chest x-ray showed diffuse small nodular infiltrates throughout both lung fields. Laboratory studies disclosed the following values: Hb 4.6 g/dl, Ht 13.9%, reticulocyte 11.5%, direct and indirect Coombs' test positive, haptoglobin 38 mg/dl, ESR 145 mm/hr, cold agglutinin titer 1:2,048 mycoplasma antibody titer 1:640, PPD negative. The diagnosis of autoimmune hemolytic anemia associated with Mycoplasma pneumonia was made, and treatment with minocycline and prednisolone observed striking clinical improvement. It was suggested that the cold exposure was possibly a major factor in the pathogenesis of hemolysis in this patient. PMID- 1433921 TI - [A case of monoblastic crisis of CML beginning with extramedullary tumor formation in a rib]. AB - A patient with CML showed monoblastic crisis which started with extramedullary tumor formation in a rib before medullary involvement. She was diagnosed as having CML in 1984 at the age of 57. In February 1990, she was admitted to Furukawa City Hospital because of extramedullary blastic crisis beginning at the right 5th rib. At that time, the bone marrow revealed 4.6% blasts. On March 5, after one course of chemotherapy, she was transferred to our hospital for radiotherapy. Hematological findings were WBC 10,100/microliter with 10% blasts, Hb 10.9 g/dl, platelet 3.7 x 10(4)/microliters. Bone marrow aspiration was unsuccessful. The blasts in the peripheral blood were negative for peroxidase and chloroacetate esterase; but positive for naphtylbutyrate esterase. The leukemic cells were positive for CD13, CD33, and had phagocytic activity. Chromosomal analysis revealed 46XX with Ph1 chromosome and some additional anomalies. Southern blot analysis of tumor cells shows BCR rearrangement. These findings suggest that the blasts were immature monocytic cells, and we conclude that this is a rare case of extramedullary monoblastic crisis of CML. PMID- 1433922 TI - [Changes in bone marrow MRI patterns in aplastic anemia before and after successful treatment with ATG]. AB - In order to evaluate the usefulness of MRI in estimating bone marrow cellularity, we performed MRI of the lumbar spine in two patients with severe aplastic anemia, before and after successful treatment with antithymocyte globulin (ATG). Case 1, a 25-year-old man with idiopathic aplastic anemia, was treated with ATG 6 months after the onset. One month after treatment, his peripheral blood count and bone marrow cellularity recovered, and the MRI bone marrow pattern became normal. Case 2, a 78-year-old woman with drug-induced aplastic anemia, was treated with ATG 4 months after the onset. Three months after treatment, her peripheral blood count improved. Five months after treatment, her bone marrow cellularity recovered and the MRI bone marrow pattern was normal for her age. Seven months after treatment, when her peripheral blood count was almost normal, we observed hypercellular bone marrow restoration at the periphery of the vertebrae. MRI seems to be an effective method of evaluating bone marrow recovery in aplastic anemia. PMID- 1433923 TI - [A case of T-cell prolymphocytic leukemia]. AB - A 54-year-old man who had been known to have a high prolymphocyte count for four years was admitted to our hospital because of dyspnea in September, 1990. Physical examination revealed skin eruption, lymphadenopathy and hepatosplenomegaly. Chest X-ray demonstrated bilateral pleural effusions. The leukocyte count was 232,900/microliter with 99% lymphoid cells possessing single nucleoli. The cells expressed the phenotype CD2+, CD3-, CD4+, CD7+, and CD8-. Southern blot analysis of DNA from these cells revealed monoclonal rearrangement of T-cell receptor beta-chain genes. Anti-human T-cell lymphotropic virus type 1 (HTLV-1) antibody and HTLV-1 proviral DNA were not detected. A biopsy specimen from the skin lesions showed infiltration of the leukemic cells which were positive for anti-MT1 antibody. Histological finding of the axillary lymph node was malignant lymphoma, diffuse, medium-sized, T-cell type. Combination chemotherapy resulted in the improvement of skin eruption, lymphadenopathy, hepatosplenomegaly and pleural effusions, although his prolymphocyte count increased to 910,000/microliters. He died of cerebral bleeding in July, 1991. We diagnosed this case as T-cell prolymphocytic leukemia, observed for five years. PMID- 1433924 TI - [Norfloxacin-induced infectious mononucleosis (IM)-like syndrome with Stevens Johnson syndrome]. AB - A 77-year-old male who had suffered from an upper respiratory infection and had been given Norfloxacin (NFLX) on May 2, 1990, developed generalized erythema which did not subside with prednisolone. He was hospitalized on May 8, and Stevens-Johnson syndrome was diagnosed. The WBC was 115,400/microliter (Ly 61.0%, Aty Ly 39.5%). Sternal tap revealed hypercellular marrow with increased lymphocytes (48.5%; Aty Ly 24.5%) and eosinophils (7.0%). Clinical chemistry revealed slightly abnormal liver and renal function with LDH (1,745 IU/l) and IgE (803 IU/ml) elevation. No pathognomonic result was obtained with several viral antibodies. CD4+, CD8+ lymphocytes and the 4/8 ratio were 39%, 43% and 0.9, respectively. Clinical and laboratory abnormalities were normalized within 3 weeks after the discontinuance of all drugs. Positive lymphocyte stimulation test results were obtained by NFLX. While drug allergy is known to be a cause of IM like syndrome, there are few reports regarding the subset characterization of the increased T lymphocytes. In this case, T lymphocytosis was remarkable, but the 4/8 ratio declined only slightly, indicating that CD4+ as well as C8+ cells were activated and increased, unlike IM. The record of this case helps to clarify the mechanisms of the lymphocyte activation shared and not shared by EBV-induced IM and IM-like syndrome. PMID- 1433925 TI - [Malignant lymphoma occurring subsequent to autoimmune disease]. AB - The authors report six cases of non-Hodgkin's lymphoma (NHL) (3B-cell type, one T cell type, one non-T non-B cell type, one unclassified type) occurring subsequently to autoimmune diseases. The patients were females aged 43 to 70 (median 61). Rheumatoid arthritis was most frequent as the preceding autoimmune disease, and the intervals from the onset of an autoimmune disease to that of NHL were 10 to 36 years (median 20). Polyclonal hypergammaglobulinemia was seen in 4 cases, lymphocytopenia in 3 cases, and conversion to negative PPD reaction in 2 cases. Only one patient had been given corticosteroids, and immunosuppressive agents may not contribute much to the development of lymphoma in patients with autoimmune diseases. PMID- 1433926 TI - [Chronic lymphocytic leukemia diagnosed after corticosteroid therapy for Evans syndrome]. AB - A 59-year-old woman was admitted in February 1991, because of abdominal distension. On admission, she had splenomegaly, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura. Evans syndrome had been diagnosed and daily prednisolone therapy had been performed. After this therapy, a rapid increase of lymphocytes was observed accompanied with contraction of spleen. The monoclonal proliferation of B-lymphocytes and rearrangement of JH and J kappa gene were detected and chronic lymphocytic leukemia was diagnosed. With reduction of prednisolone, the lymphocyte counts decreased and the size of the spleen returned to the previous state. It is suspected that the cause of rapid lymphocytosis in this case was due to the redistribution of lymphocytes from the spleen to the peripheral blood. PMID- 1433927 TI - [Interleukin-6 in hematological diseases with septic shock]. AB - The authors measured the level of interleukin-6 (IL-6), endotoxin and CRP from 7 patients of documented sepsis with hematological disorders. IL-6 was higher in patients who developed septic shock, compared with patients who had only sepsis. These data revealed the importance in the level of IL-6, rather than endotoxin and CRP, in managing the patients with septic shock. PMID- 1433928 TI - [Malignant lymphoma with subdural effusion]. AB - A 64-year-old woman was admitted for treatment of malignant lymphoma involving the pharynx and abdomen. Lymphoma disappeared after chemotherapy and radiotherapy, but she had central nervous system symptoms; euphorism, left facial nerve palsy, right hemiplesia, and disturbance of micturition. Magnetic resonance imaging (MRI) revealed a diffuse dural thickening and a subdural fluid retention. The subdural fluid was determined to be an exudate, and a biopsy of the dura mater revealed a normal dura and a fibrin clot containing lymphoma cells and neutrophils. MRI can be very useful to detect the meningeal involvement of malignant lymphoma. PMID- 1433929 TI - [Autoimmune hemolytic anemia induced by alpha-interferon therapy in a case of IgG kappa type multiple myeloma]. AB - A 47-year-old male case of IgG-kappa type multiple myeloma was treated with VMCP and recombinant human alpha-interferon (IFN-alpha 2a). The direct Coombs test was positive before treatment. Hemolytic anemia associated with massive hematuria was observed during the administration of 9 million IU IFN-alpha 2a per day for 2 weeks. The hemolytic symptoms rapidly improved after withdrawal of IFN-alpha 2a. This clinical course suggests that IFN-alpha as an immunomodulator was responsible for the progression of autoimmune hemolytic anemia in a case of multiple myeloma. PMID- 1433930 TI - [A case of primary malignant lymphoma of the uterine body]. AB - A 70-year-old female was found to have class V cytology on an endometrial smear, and a histological diagnosis of malignant lymphoma was made by endometrial biopsy. The pathological diagnosis was malignant lymphoma, diffuse large cell type according to the Working Formulation classification. Immunohistochemical staining showed lymphoma cells to be positive for CD 20 (B 1), indicating B cell lineage. Two cervical lymph nodes were palpable, and swelling of a para-aortic lymph node was also found by abdominal CT scan. The clinical stage was determined to be III according to the Ann Arbor classification. After three courses of CHOP chemotherapy, lymphoma cells could no longer be detected by endometrial biopsy, and the para-aortic and cervical lymphadenopathy also disappeared. Primary malignant lymphoma of the uterus, especially of the uterine body, is very rare. Only eight cases of primary malignant lymphoma of the uterine body were reported in the literature. The cell lineage was decided in only one case, which was B cell type. PMID- 1433931 TI - [Leukemic blast colony assay in studies of progenitor cells from acute myeloblastic leukemia and its clinical application]. PMID- 1433932 TI - [Analysis of adhesive proteins on the surface of platelets from the patients with lung cancer: studies in histological type and clinical stage]. AB - Flow cytometry was used to detect platelet-associated fibrinogen (PA-Fbg), platelet-associated fibronectin (PA-FN) and platelet-associated thrombospondin (PA-TSP) on the surface membrane of platelets and plasma (P)-TSP in 30 patients with lung cancer (16 case of adenocarcinoma and 14 of squamous cell carcinoma). ELISA was used to analyze beta-TG and PF4. In the lung cancer group, beta-TG and PF4 were higher than those of a normal control group. PA-Fbg values were correlated with beta-TG and PF4 values. Each adhesive protein had a higher value in the patient than in the normal control group, and the degree of the increase was related to the progression of clinical disease stage. In the squamous cell carcinoma group, the P-TSP value was significantly elevated. Platelet size increased as the clinical stage of the disease progressed. These results suggest the following: 1. An increase in PA-Fbg can indicate the presence of activated platelets. 2. In patients with lung cancer, activated platelets appear in the blood, and their numbers increase as the clinical stage of the disease progresses. 3. Differences in histologic type led to differences in binding adhesive protein. PMID- 1433933 TI - [Renal and electrolyte disturbances in chronic myelogenous leukemia]. AB - Renal and electrolyte disturbances in 91 patients with chronic myelogenous leukemia (CML) were analyzed over a period of these twenty years. At diagnosis, renal and electrolytes were studied in 72 patients including 65 in chronic cases, 5 in accelerated phase and 2 in blastic crisis. There were 8 cases of hypocalcemia among 62 patients and 5 cases of hyperphosphatemia among 48 patients. The cases of hyperphosphatemia and renal dysfunction had short median survival. There were no significant differences of renal and electrolyte disturbances between before and after chemotherapy. Various electrolyte disturbances, that is, hyponatremia, hypo-, hyperkalemia, hypocalcemia, hypo-, hyperphosphatemia, were found in the blastic crisis of CML. In the last admission, renal dysfunction and various electrolyte disturbances were present in almost half of the cases. Pathological studies were performed in 18 autopsy cases. Acute tubular insufficiency or necrosis, hypercalcemic nephropathy, and renal infiltration of leukemic cells were recognized in patients who had renal dysfunction. PMID- 1433934 TI - [Studies of human bone marrow stromal cells--effects of antimetabolites on the growing dynamics of human bone marrow cells and their support of hemopoietic cells]. AB - The effects of antimetabolites on the growing dynamics of human bone marrow stromal cells and their support of hemopoietic cells were tested by using a modified version of Dexter's culture system. Cytosine arabinoside (ara-C) was found to suppress neither the growing dynamics nor the supportability. On the other hand, methotrexate (MTX) suppressed the supportiveness, even though it hardly suppressed the growing dynamics. The recognition of injury to marrow cells could be of potential importance in cancer chemotherapy. Our in vitro evidence may provide clinical insights for cancer chemotherapy including prolonged marrow suppression or pretreatment of bone marrow transplantation. PMID- 1433935 TI - [Clinical significance of serum erythropoietin levels in patients with multiple myeloma]. AB - Serum erythropoietin (Epo) levels were measured in 53 patients with multiple myeloma (MM), 49 normal subjects and 53 patients with some hematological diseases including aplastic anemia (AA), iron deficiency anemia, etc. to study the significance of erythropoietin in anemia of MM. The serum Epo level was 72.0 +/- 94.4 mIU/ml (mean +/- SD) in MM patients, which was significantly higher than in normal subjects (24.1 +/- 6.1 mIU/ml), but lower than in AA patients (7069.9 +/- 9406 mIU/ml). A significant inverse correlation was found between the hemoglobin (Hb) levels and the logarithmic values of serum Epo levels (r = -0.543, p < 0.05) in MM patients. This inverse correlation was stronger (r = -0.636, p < 0.05) in MM patients without renal dysfunction than in whole MM patients, while no correlation was observed in MM patients with renal dysfunction. These results indicate that MM patients with renal dysfunction have a low ability to synthesize Epo and that the supplemental therapy of recombinant Epo is effective to improve their anemia. In addition, the circadian rhythm of serum Epo level was lower in the morning than in the afternoon in both MM patients and normal controls. Serum Epo levels after chemotherapy in MM patients were elevated temporarily and then decreased in spite of no change of blood Hb level. PMID- 1433936 TI - [Urinary excretion of parathyroid hormone-related protein in patients with adult T-cell leukemia and other hematologic disorders]. AB - Urinary excretion of parathyroid hormone-related protein (PTH-rP) was measured by radioimmunoassay in 25 patients with adult T-cell leukemia (ATL), in 68 patients with other hematologic disorders and in 13 asymptomatic individuals seropositive for human T-cell leukemia virus type I (HTLV-I). The mean levels of urinary PTH rP in ATL patients with hypercalcemia (11.01 micrograms/g.Cr) were higher than in ATL patients with normocalcemia (5.16 micrograms/g.Cr). The mean levels in patients with acute type (8.84 micrograms/g.Cr), lymphoma type (4.18 micrograms/g.Cr) and crisis ATL (18.20 micrograms/g.Cr) were significantly higher than in urine of healthy controls. However, all asymptomatic carriers of HTLV-I and patients with chronic and smoldering ATL had normal urinary PTH-rP levels. In 7 patients with acute myelogenous leukemia, 1 patient with blastic crisis of chronic myelogenous leukemia and 3 patients with malignant lymphoma, the urinary levels of PTH-rP were above the normal range. Urinary levels of PTH-rP of the ATL patients with hypercalcemia correlated with the serum calcium levels. Urinary levels of PTH-rP of the all ATL correlated with serum lactic dehydrogenase level. These findings suggest that the measurement of urinary levels of PTH-rP is useful for evaluation of ATL and that some tumor cells of other hematologic diseases may produce PTH-rP. PMID- 1433937 TI - [Prophylaxis of thrombosis in a pregnant woman with congenital antithrombin III deficiency: changes in hemostatic molecular markers before the onset of thrombosis]. AB - A pregnant woman with congenital antithrombin III (AT III) deficiency was given AT III concentrate and warfarin at the first and after 36th week of gestation periods and at the other gestation period, respectively. The patient developed thrombosis in the left leg, but fibrinopeptide A (FPA) and thrombin-AT III complex (TAT) had already shown high values one week before, suggesting the possibility of their being forecast markers of thrombosis. The administration of AT III concentrate caused an improvement in thrombosis. Therefore, in case of high FPA and TAT values as determined one or two times a week, the administration of AT III concentrate was thought necessary. In case of warfarin, however, non administration during the 6th-9th weeks of gestation for the purpose of avoiding teratogenicity and frequent blood coagulation tests taking heed of overdosage for the purpose of avoiding fetal central nervous system abnormalities were suggested necessary. Delivery was uneventful, both mother and child being doing very well; umbilical blood AT III activity was 18%. It is generally difficult for us to form the diagnosis as AT III deficiency only from AT III activity at neonatal stage, but in the present study, we analyzed the restriction fragment length polymorphism of the AT III gene using umbilical blood, and succeeded in diagnosing the neonatal child as AT III deficiency. PMID- 1433938 TI - [Effect of subcutaneous administration of interleukin-1 beta on blood platelet count and serum GM-CSF in patients with myelodysplastic syndrome and aplastic anemia]. AB - Subcutaneous administration of recombinant human Interleukin-1 beta (IL-1 beta) in a dose of 1-3 x 10(4) U/day for 14 to 72 days resulted in an increase in circulating granulocytes and bone marrow monocytes in all the 4 patients examined. Circulating platelet count was also increased in two of four patients with myelodysplastic syndrome (MDS) and aplastic anemia (AA). Bone marrow examination revealed an increase in megakaryocyte count in these patients, whereas the percentage of blast was not changed. An increase in blood platelet count was accompanied by an increase in serum GM-CSF in a patient with AA, whereas serum IL-6 level was not changed throughout the treatment with IL-1 beta. These findings suggest that IL-1 beta may be useful for the treatment of a proportion of patients with MDS and AA who are associated with thrombocytopenia. PMID- 1433939 TI - [Clinical significance of antinuclear antibody in patients with idiopathic thrombocytopenic purpura]. AB - The clinical significance of antinuclear antibodies (ANA) in patients with chronic idiopathic thrombocytopenic purpura (ITP) was evaluated. Serum samples of 55 patients with ITP without clinical features of systemic lupus erythematosus (SLE) were examined. The average follow-up period was 5.5 years. Positive ANA was found in 23 of the 55 patients. Twelve of these 23 showed a high-titer of ANA. There was no difference in platelet counts between ANA positive patients and negative patients, and there was no correlation between platelet counts and antibody titers. Ten of the 23 positive sera had precipitating antibodies to nuclear antigens; 7 SS-A and 3 RNP antibodies. The platelet counts of the 7 cases with anti-SS-A antibody positive were slightly low compared with those of the anti-SS-A antibody negative patients. None of the 10 patients developed SLE during the average follow-up period of 8.1 years. These results suggest that ITP patients who have a high-titer of ANA or antibody against SS-A do not always develop SLE. It was concluded that ANA with a high titer or precipitin to nuclear antigens, particularly SS-A, dose not predict a high risk of developing SLE in the future. PMID- 1433940 TI - [Clinical significance of aldolase A in sera of patients with leukemia]. AB - Serum aldolase A (ALD-A) levels were determined in patients with leukemia using a radioimmunoassay method. The method is a double antibody radioimmunoassay consisting of purified ALD-A as ligand, chicken antisera to ALD-A and rabbit antibodies to chicken IgG. Serum ALD-A levels of 41 normal healthy subjects ranged from 130 to 210 ng/ml (mean +/- 2 SD; 171 +/- 39 ng/ml). Serum ALD-A levels ranged from 90 to 200 ng/ml in patients with 42 non-neoplastic hematological diseases with the exception of hemolytic anemia. In contrast, 61 patients with acute leukemia before treatment exhibited increased serum ALD-A levels ranging from 125 to 1,550 ng/ml, with a mean value of 480 ng/ml. Serum ALD A levels in 24 patients with chronic myelocytic leukemia (CML) during the chronic phase also exhibited high mean values of 481 ng/ml in a range of 270 to 1,100 ng/ml. Serum ALD-A levels were higher than 210 ng/ml in 85.2% of the patients with acute leukemia and in all patients with CML. Serum ALD-A levels tended to be decreased within the normal range, if those patients could achieve complete remission. In contrast, serum ALD-A levels showed a tendency to increase if those patients experienced a relapse of leukemia. These results suggest that the measurement of serum ALD-A levels by radioimmunoassay is useful for diagnosis and prediction of relapse in patients with leukemia. PMID- 1433941 TI - [The measurement of erythrocyte zinc protoporphyrin/heme ratio in various anemias in childhood]. AB - The measurement of erythrocyte zinc protoporphyrin (ZPP) with a hematofluorometer is known to be a simple and cost-effective method to screen iron deficiency and lead poisoning. We measured ZPP on blood samples from 201 children suffering from various diseases, which revealed that ZPP has better sensitivity and specificity for identifying iron deficiency than serum ferritin and percent transferrin saturation. ZPP levels in various anemias were also measured. ZPP rose markedly (> 200 mumol/mol heme) in untreated iron deficiency anemia and returned to normal in 3-4 months since the initiation of iron therapy. Moderate elevation of ZPP was observed in acute leukemia (at onset and during induction therapy), MDS, aplastic anemia and some other anemic conditions. These findings suggest that erythrocyte ferrochelatase may be unexpectedly affected in anemias even except lead poisoning. PMID- 1433942 TI - [Idiopathic thrombocytopenic purpura associated with pregnancy]. AB - We examined 14 patients (18 cases) with idiopathic thrombocytopenic purpura (ITP) during pregnancy at our department. ITP, which had improved, recurred during pregnancy in 4 cases while it developed for the first time during pregnancy in 10 cases. In the other 4 cases, pregnancy occurred in the course of ITP. Although a normal infant was born in 14 cases, 3 stillbirth and a premature infant was observed in 4 cases. Six deliveries had some toxemia of pregnancy. A transient decrease in neonatal platelets was observed in 4 of 14 cases and mother's platelets count was less than 40 X 10(3)/microliters in the 4 cases. Although antinuclear antibody, Coomb's test and antiphospholipid antibody were positive in some cases, these were not markedly related to clinical course or neonatal platelets count. Eleven cases were treated with glucocorticoids, high dose gamma globulin or platelets transfusion, but 11 cases were not treated. Since ITP is frequently observed during pregnancy and may be some risk factor for pregnancy, treatment of ITP is important during pregnancy. PMID- 1433943 TI - [Cyclic thrombocytopenia with chronic thyroiditis and ankylosing spondylitis]. AB - A 58-year-old man with cyclic thrombocytopenia who was initially diagnosed as idiopathic thrombocytopenic purpura (ITP), concomitant with chronic thyroiditis and ankylosing spondylitis, was reported. Serum level of T 3 (0.48 ng/ml) and T 4 (2.1 micrograms/ml) were both subnormal and that of TSH (257.1 microU/ml) was markedly elevated. Thyroid test (6400X) and microsome test (6400X) was both positive, but anti-nuclear antibodies were negative. Radiographic findings of lumbar spine showed the typical "bamboo spine" and HLA B 27 was positive. Therapies for ITP, such as adrenocorticosteroids including steroid pulse therapy, high-dose intravenous gamma-globulin, danazol, slow infusion of vinca alkaloids and splenectomy, were only effective transiently. After these therapies platelet counts began to fluctuate from 0.4 X 10(10)/L to 34.4 X 10(10/L, therefore the diagnosis of cyclic thrombocytopenia was done. Interestingly low-dose methotrexate (MTX) was effective, and the cyclic fluctuation of platelet counts disappeared. These observations in this case were very suggestive of the pathogenesis of cyclic thrombocytopenia and mechanisms of cyclic change of platelet counts. PMID- 1433944 TI - [A case report of childhood acute lymphoblastic leukemia with leukoencephalopathy that responded to oxygenation under hyperbaric pressure therapy]. AB - In this report, we described a case of acute lymphoblastic leukemia with leukoencephalopathy that responded to oxygenation under hyperbaric pressure (OHP) therapy. The patient was 6 year-old female who was diagnosed as acute lymphoblastic leukemia (ALL) one year and 9 months earlier. After the first relapse of the central nervous system (CNS) leukemia, intrathecal administration of methotrexate (MTX) and skull irradiation induced CNS remission. The patient was readmitted because of second CNS relapse. After the third administration of weekly intrathecal MTX injection, apathy and finger tremor were observed. Her conscious disturbance continued for two weeks and magnetic resonance imaging (MRI) revealed abnormal findings in the white matter of her brain. Subsequently OHP therapy was commenced, and the conscious disturbance was improved gradually. One month later, neuro-disturbance resolved completely and the findings of MRI were improved. We could not find any case of leukoencephalopathy which was treated with OHP in the literature. But our case suggested that OHP therapy is valuable in patient with leukoencephalopathy in the early stage. PMID- 1433945 TI - [Disappearance of Philadelphia chromosomes after remission induction in lymphoid crisis of chronic myelogenous leukemia]. AB - The authors report a rare case of chronic myelogenous leukemia (CML) in which the Ph1 clone disappeared after remission induction of lymphoid crisis. A 58-year-old man was admitted to our hospital because of fever in July 1988. The white cell count was elevated. Bone marrow aspirate showed hypercellularity with myeloid hyperplasia. In the chromosomal analysis, Ph1 chromosomes were detected in 100% of bone marrow cells analysed. Diagnosis of CML was made and treatment was initiated with recombinant interferon-alpha 2a. Hematological remission without cytogenetic improvement was achieved. In March 1990 he developed lymphoid crisis with proliferation of CD10-positive cells. The chromosomal analysis revealed additional abnormalities including, 45, X, -Y, t(9;22) (q34;q11), +1, -8. With vincristine 0.6 mgX4, pirarubicin 15 mgX4, dexamethasone 40 mgX4 therapy complete remission was obtained. In December 1990 the Ph1 positive clone completely disappeared judging from normal karyotypes in the chromosomal analysis and the disappearance of M-bcr gene rearrangement. PMID- 1433946 TI - [Effective treatment of CMMoL with F-COP (epirubicine, cyclophosphamide, vincristine, prednisolone) therapy]. AB - A 66-year-old female was admitted with high fever and loss of consciousness. For the past one year, she has experienced recurrent febrile episodes. On admission, the presence of monocytosis, thrombocytopenia of the peripheral blood and dysplastic findings of the bone marrow cells indicated chronic myelomonocytic leukemia (CMMoL). The high fever persisted in spite of treatment with antibiotics. Although she was treated by pulse therapy with methyl-prednisolone, her clinical symptoms did not improve. Pleural effusion and ascites were also noted. Treatment with F-COP (epirubicine, cyclophosphamide, vincristine, prednisolone) therapy, resulted in a dramatic improvement of her condition. The F COP therapy was given monthly for the next 7 months. This case suggests that F COP therapy may be effective for some patients with CMMoL. PMID- 1433947 TI - [Hodgkin's disease presenting with fever of unknown origin associated with granulomas of the bone marrow]. AB - A 73-year-old man was admitted to our hospital on April 30, 1990, because of fever persisting for 18 months. Bone marrow puncture and biopsy were performed, because examination on admission revealed an elevated leukocyte count and anemia while his superficial lymph nodes, liver and spleen were not palpable. The results of the bone marrow biopsy revealed evidence of granuloma. Around May 10, the patient developed hepatosplenomegaly and enlargement of left cervical lymph nodes. Based on the results lymph node biopsy, a diagnosis of Hodgkin's disease was made, and CHOP therapy was instituted on May 20. However, the patient developed interstitial pneumonia and died on July 3. This patient's disease was manifested by fever of unknown origin. Bone marrow biopsy revealed granuloma with histiocytes predominating, and the patient subsequently developed lymph node enlargement. His disease was then diagnosed as Hodgkin's disease on the basis of a biopsy. Malignant lymphomas associated with granulomas in the bone marrow, liver or spleen are for the most part found in the advanced stage of the disease. It should be borne in mind, however, that some patients may exhibit granuloma formation in their bone marrow prior to lymph node enlargement or hepatosplenomegaly, as in the present case. PMID- 1433948 TI - [Isolated cerebellar tumor formation in a patient with blastic crisis of chronic myelogenous leukemia]. AB - A 42-year-old male was diagnosed as having Ph-positive chronic myelogenous leukemia (CML) in 1988. He had been treated with ranimustine and interferon alpha. In April 1990, he was admitted to our hospital because of hemorrhagic diathesis. Blood counts revealed a white blood cell count of 319,200/microliters with 12 per cent blasts, a hemoglobin level of 9.2 g/dl, and a platelet count of 48,000/microliters. The bone marrow aspiration revealed hypercellularity with 68.2 per cent blasts, and chromosomal analysis showed 48, XY, +8, double Ph. A combination chemotherapy containing vindesine, cytarabine and prednisolone was administered. Four days later, he suddenly complained of headache and vertigo. CT scan of the brain showed a high density area at the cerebellar vermis. He was then treated with intensive combination chemotherapy including enocitabine, daunomycin, 6-mercaptopurine and prednisolone. He attained a hematological response and clinical improvement temporarily, as the cerebellar tumor regressed. In September he had headache and vertigo again, and CT scan revealed a rapid increase in size of the cerebellar tumor. Local irradiation with total doses of 19 Gy brought about a partial resolution of the lesion, and relief from the symptoms. In November, his hematological conditions deteriorated gradually and he died of brain hemorrhage on November 22, 1990. Post-mortem examination disclosed a 1 x 1 cm sized mass in the cerebellar vermis which showed a fibrous change surrounded with hemosiderin-laden macrophages microscopically. We reviewed the eight reported cases of CML with intracranial tumors, and discussed the factors which had contributed to the prolongation of survival in our patient. PMID- 1433949 TI - [Treatment of CML with blastic crisis by the combination therapy of VP and low dose Ara-C]. AB - Forty-three-year-old man with schizophrenia, who had been diagnosed as chronic myelogenous leukemia (CML) and had been treated with hydroxyurea for 3 months, developed blastic crisis. The cytochemical study of the blastic cells showed POX (+), SBB (+) and TdT (+). The surface marker analysis revealed that the blastic cells expressed both myeloid (CD13, 33) and lymphoid (CD10, 19) markers. In the chromosomal analysis, additional chromosomal abnormality (11q+) was detected in all cells analysed (20/20) in addition to the standard type Ph1 chromosome. He was diagnosed as bi-phenotypic blastic crisis, and vincristine-prednisolone therapy was started. Initially, he responded to VP therapy well, but gradually became refractory to the therapy after 5 courses of VP. As many myeloblasts containing azurophilic granules were seen in the bone marrow after VP therapy, low dose Ara-C therapy was combined to VP. After 21 days of low dose Ara-C and VP, the percentage of the blast in the BM was significantly decreased and normal myeloid differentiation was observed after transient BM suppression. The chromosomal analysis showed the partial reappearance of standard Ph1 chromosome in 55% of the cells analyzed (11/20). Taken together, our data suggested that the combination of VP and low-dose Ara-C therapy might have some therapeutic benefit for the treatment of the CML with blastic crisis. PMID- 1433950 TI - [Successful interferon-alpha treatment of hepatitis B developing during chemotherapy of malignant lymphoma]. AB - In a 47-year-old male patient a tonsillar swelling was pointed out in May, 1991. Lymph node biopsy revealed that he had malignant lymphoma (diffuse large cell type). He had no hepatic dysfunction on admission, but because of positive hepatitis B (HB) antigen and negative HB antibody, he was diagnosed as an asymptomatic HB carrier. The staging examination showed that he had stage IIA lymphoma. Treatment with the COP-BLAM regimen was initiated on June 8. But the level of serum GOT and GPT increased to 286 IU/l and 392 IU/l, respectively. Serum DNA polymerase also increased to 9492 cpm. Interferon-alpha (3 x 10(6) units daily) was administered intramuscularly from June 8. Serum DNA polymerase decreased to zero on September 2, and his HBe antibody became positive indicating seroconversion. COP-BLAM chemotherapy without prednisolone was initiated from September 9 and complete remission was achieved. He was discharged from our hospital on September 25. It has been frequently reported that asymptomatic HB antigen carriers developed fulminant hepatitis during the course of chemotherapy. Our case suggests that it is necessary to continue chemotherapy in order to attain seroconversion by early use of interferon-alpha, when lymphoma patients display aggravated hepatic dysfunction and increased DNA polymerase levels. PMID- 1433951 TI - [HIV-1 seropositive hemophilia A complicated by disseminated intravascular coagulation syndrome and acute pancreatitis during treatment of Pneumocystis carinii pneumonia]. AB - Pneumocystis carinii pneumonia (PCP) is a major opportunistic infection in acquired immunodeficiency syndrome (AIDS) and is treated with co-trimoxazole, pentamidine and others. The severe adverse reactions, including bone marrow suppression, by these therapeutic agents often preclude their continued use. A 14 year-old male HIV-positive hemophilia A patient, who was complicated by disseminated intravascular coagulation syndrome (DIC) following acute pancreatitis during treatment for PCP, was treated with proteinase inhibitors and anticoagulant agents. He was improved and discharged. As pentamidine may cause pancreatitis and develop DIC, it is important that pancreatic enzymes should be carefully followed when this agent administrated. In this case, granulocyte colony-stimulating factor and erythropoietin were effective for the bone marrow suppression, suggesting that importance of these agents for the prophylaxis of other secondary infections during the treatment. PMID- 1433952 TI - [Clinicopathological review of Japanese cases with neoplastic angioendotheliosis]. AB - The patient was a 76-year-old female who had been referred to our hospital because of fever of unknown origin on October 15, 1987. On admission, the body temperature was 38.6 degrees C and atonic palsy of the left upper limb was noted. Abnormal laboratory findings included CRP5+, an increase in LDH, Hb 7.9 g/dl. The cause of the fever could not be identified. The fever did not respond to various treatment. The patient developed DIC in late October and died on November 5. In autopsy histological examination revealed tumor cells in the vessels of the generalized organs. A diagnosis of neoplastic angioendotheliosis (NAE) and immunohistologically B lymphoma was made. We reviewed the literature on 37 Japanese cases of NAE. The cases, consisting of 19 males and 18 females, were aged 37-87 years with a median value of 60 years. The symptoms observed during the course were most frequently mental or neurological symptoms and fever, and rash was uncommon. Laboratory findings were non-specific and biopsy was needed for definitive diagnosis. By autopsy, lesions were noted more frequently in the brain, kidneys, and lungs, and the findings in the skin were indeterminate. These observations suggest that when NAE should be considered, kidney, lung or skin biopsy should be performed for definitive diagnosis. PMID- 1433954 TI - [Pleiotropy and redundancy of cytokines]. PMID- 1433953 TI - [Lumbago as a presentation of B-cell lymphoma invading psoas muscle]. AB - A 73-year-old male had severe lumbago and right inguinal lymphadenopathy. A CT scanning of his abdomen showed marked enlargement of right psoas and erector spinae muscles. The biopsies of the lymph node and the muscles revealed non Hodgkin's lymphoma of follicular mixed type with muscle invasion. THP-COPE therapy was begun. The swelling of the muscles diminished and the lumbago resolved rapidly. It was reported that clinically prominent infiltration of of lymphoma in skeletal muscle was rarely and psoas muscle was for the most part. We have to consider that psoas muscle invasion of lymphoma cause hard to cure lumbago. PMID- 1433955 TI - [Present status and future aspects of clinical use of cytokines]. PMID- 1433956 TI - [Mechanism of cytokine pleiotropy and mutual regulation]. AB - Cytokines manifest overlapping effects on many cell types and their production is regulated by a cytokine network. This minireview summarizes the current understanding of how affinity converter molecules, shared by several cytokines, is related to cytokine pleiotropy, and how Th1/Th2 are differentially developed and regulated through a cytokine network, especially, negative loop. Finally, the importance of the temporal expression of cytokines, in relation to the physiological relevance of the network, is pointed out. PMID- 1433957 TI - [Regulation of proliferation and differentiation of hematopoietic cells by cytokines]. AB - Recent studies on the hematopoietic system have revealed that both constitutive and inducible hematopoiesis are regulated by complicated networks composed of various kinds of cytokines and that there are some general rules for hematopoietic cytokine biology. Further accumulation of knowledge about the regulation of proliferation and differentiation of hematopoietic cells by cytokines will serve to clarify the pathophysiology of hematological diseases, resulting in the development of therapeutic strategy for these diseases. PMID- 1433958 TI - [Regulation of immune response by cytokine network]. AB - Cytokines are a highly diverse group of intracellular messages. Many cDNAs that encode the cytokines have been cloned in 1980's and the structure of the molecules have been determined. The main function of the cytokines is to amplify the immune and inflammatory responses, keeping them under control at the same time. They orchestrate the response and maintain a proper balance among the various cell types. In this chapter, we summarized the immunoregulation by cytokine network, focussing on the control of antibody production and immunoglobulin class switch by various cytokines produced by helper T cell subsets. PMID- 1433959 TI - [Inflammation and pro-inflammatory cytokine]. AB - The main pathological feature of inflammation consists of leukocyte infiltration and exudation of plasma into the lesion in the early stage followed by proliferation of connective tissue including fibroblasts, which leads to the formation of granulation tissue. Systemic manifestations include elevation of body temperature and increase of serum acute phase reactants such as C-reactive protein and serum amyloid A. Most of these reactions are presumed to be caused by mediators which are produced by a various kinds of cells and tissues upon contact with inflammatory stimuli, such as bacteria, helminths, viruses, etc. Recently, it has become known that most of inflammatory stimuli induce the production of large amounts of several cytokines including interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF) alpha and that these cytokines exert a wide variety of effects to accelerate inflammation. Hence, these cytokines are called "pro inflammatory cytokines". These cytokines have overlapping biological functions and induce the production of each other, thus forming a complicated cytokine network. Here, in order to review the roles of these cytokines in the progression of inflammation, the effects on the body temperature, leukocyte infiltration and production of serum acute phase reactants, in particular, will be discussed. PMID- 1433960 TI - [Membrane receptors and cell transformation]. AB - Here I discuss quantitative and qualitative activation of several receptor-type molecules in tumor cells. Recently we have shown that EGF-R gene is frequently mutated in human glioblastoma. Mutant EGF-R had a 801-bp deletion within the ligand binding domain, and showed a ligand-independent, constitutive elevation of tyrosine kinase activity. This EGF-R mutation is detected only in glioma and associated with gene amplification, suggesting a relationship in the molecular mechanism between deletion mutation and initiation of gene amplification in these cases. Secondly I have shown an activation of mouse CD43 gene by amplification and rearrangement in erythroleukemia cell lines. Intracellular domain of CD43 has no kinase domain but a highly conserved structure among mammals, probably interacting with intracellular signal transducers. Recently CD43 has been demonstrated to be specifically associated with a cell-adhesion molecule ICAM-1. Thus, CD43-ICAM-1 system might be a new type of cytokine system which regulate cell-proliferation through cell-cell interaction. In addition, activation of EpoR and v-mpl is also discussed. PMID- 1433961 TI - [Antitumor cytokines]. AB - Cytokines have various kinds of functions, including immunoregulation, host defense system, induction of inflammation and pathogenesis of many diseases. One of the characteristics of cytokines is the interaction among cytokines, and they further play an important role in the defense against tumor development, although its mechanism is highly complicated. In this paper, cytokines possessing antitumor activity, are described. These are 2 categories of antitumor cytokines, immunological and non-immunological ones. As immunological cytokines, interferons, interleukin 1, 2, 4, 5, 6, 8 and 12, tumor necrosis factor and lymphotoxin, have been investigated. On the other hand, tumor-degenerating factor, tumor regressing factor, glial maturation factor, glial growth inhibitory factor, neuroblastoma growth inhibitory factor, neonatal brain derived carcinostatic factor, chondromodulin and gliostatin have been characterized as non-immunological antitumor cytokines. These cytokines interact, and the complicated network of immunological and non-immunological antitumor cytokines is formed. PMID- 1433962 TI - [New cytokines for negative growth regulation]. AB - Considerable evidence has accumulated indicating that proliferation of animal cells is regulated by a balance between positive and negative growth stimuli. To clarify molecular species and physiological roles of growth inhibitors, we have been studying cytostatic or cytotoxic proteins present in different sources, such as sera and conditioned media of cultured cells. One cytostatic and two cytotoxic factors were recently purified from normal rabbit serum and characterized. Other groups also have reported various kinds of growth-inhibitory factors. The properties of these recently reported growth-inhibitory factors and their possible significance are summarized in this article. PMID- 1433963 TI - [Growth regulation of vascular cells by cytokines]. AB - Cytokines with stimulatory or inhibitory activities for vascular cells are reviewed. Directly or via humoral factors, vascular endothelial cells interact with blood cells, such as lymphocytes, neutrophils and platelets, while smooth muscle cells do so with inflammatory cells. Various cytokines, including IL-1, 6, 7, 8, GM-, G-, M-CSF, a, b-FGF, PDGF, TGF beta, PAF, PA, PAI-1, cell adhesion molecules and endothelin are produced by endothelial cells and/or smooth muscle cells, and in turn they and cytokines produced by blood cells, act as modulators of growth or function of the vascular cells under some physico-pathological states. Vascular cells, especially, endothelial cells might thus be involved in cytokine network. PMID- 1433964 TI - [Structural similarity and signal transduction of cytokine receptors]. AB - The advent of expression cloning has established a new group of membrane glycoproteins, called the cytokine receptor superfamily. Members of this family have common structural similarities in the extracellular region and no intrinsic tyrosine kinase activity is seen in the intracellular region. A combination of two distinct subunits (alpha and beta) in the family has been shown to generate high-affinity receptors in which the alpha subunits specify the binding and the beta subunits function as transducers that are presumably associated with tyrosine kinases. The high-affinity receptors for IL-3, IL-5 and GM-CSF all share the same beta subunit. The high-affinity receptor for IL-2 is however unique in that it requires a third component, notably, the gamma subunit, whose gene we have recently cloned. PMID- 1433965 TI - [Studies of physiological functions of cytokines by generating mutant mice through the transgenic and the gene-targeting technology]. AB - Molecular cloning of gene coding for cytokines, growth factors and their receptors have facilitated an accumulation of findings regarding the function of their products. So far, many kinds of functions of such molecules in vitro have been identified. To clarify the physiological roles of such molecules in vivo a variety of cytokine-transgenic mice and a few cytokine-gene targeted mice have been generated. Many of the phenotypes expressed by these animals are as expected from the in vitro assay data, but some are unexpected. In this short article, some of the phenotypes reported are introduced and their significance is discussed. PMID- 1433966 TI - [Function, molecular structure and gene expression of interleukin-1]. AB - Recent cloning of human and murine IL-1 receptor (IL-1R) has revealed that there are at least two type of IL-1R: type I IL-1R is detected on T cells and fibroblasts and consists of 552 AAs with a cytoplasmic domain of 213 AAs, while type II is detected on B cells and monocytic cell lines and consists of 398 AAs with a short stretch intracytoplasmic domain of 29 AAs. Extracytoplasmic portion of IL-1R has some homology with vaccinia virus B15 Ag or fibroblast protein ST-2, while cytoplasmic portion has considerable similarity with Drosophila toll gene. By transfecting murine type I IL-1R cDNA into a human Jurkat cell line, structural and functional potion required for the IL-1 signal transduction is determined. At least broad portion of cytoplasmic domain including 364-474 AAs from N-terminus are found to be essential, while PKC acceptor site (Ser-431 and Ser-509), and PKA acceptor site (Ser-528) are not essential for the IL-8 gene expression. PMID- 1433967 TI - [Function, molecular structure and gene expression of IL-2 and the receptors]. AB - The Interleukin 2 receptor is now assumed to be composed of three chains, the L (alpha or Tac), H (beta) chain and p56. The L chain binds IL-2 with low affinity, whereas intermediate-affinity binding of IL-2 is achieved by an association of p56 and the H chain. The high-affinity IL-2R is therefore believed to be a quaternary complex composed of the L chain, the H chain, p56 and IL-2. A larger number of L chains enhances the association rate of IL-2 to form the high affinity IL-2R in agreement with the stepwise binding model. The signal transduction-competent H chain has been shown to associate with p56lck upon IL-2 stimulation. PMID- 1433968 TI - [IL-3 gene, receptor and signal transduction]. AB - Interleukin 3 (IL-3) plays a critical role in growth and differentiation of myeloid cells. The human IL-3 gene, located on chromosome 5 contains several cis acting DNA sequences, i.e. CLE (conserved lymphokine element) and a GC rich region, similar to the GM-CSF gene. The expression of the GM-CSF and IL-3 genes in activated T cells may be regulated coordinately through these cis-regulatory elements. Recently, reconstitution experiments using isolated cDNA clones for receptor subunits have revealed that two distinct proteins are required for the high affinity receptors for GM-CSF, IL-3 and IL-5; the alpha subunits bind with the corresponding ligands with low affinity, and the beta subunit is shared in common. Tyrosine kinase activity appears to be involved in the signal transduction of the IL-3 and GM-CSF receptors. PMID- 1433969 TI - [Function, molecular structure and gene expression of IL-4]. AB - Interleukin-4 (IL-4) is a T-lymphocyte-derived 20-kDa glycoprotein that has a broad spectrum of biological activity including growth and differentiation of T cells, B cells, mast cells, hematopoietic cells and non-hematopoietic cells. The biological effects of IL-4 are induced by binding to specific membrane receptors (IL-4R) on target cells. Molecular cloning of IL-4R revealed a novel cytokine receptor family, but not clues as to the signalling mechanism. The biochemical mechanism of IL-4 signal, induced by its specific binding, remains to be clarified. Recent studies on the physiological function of IL-4 are presented here. PMID- 1433970 TI - [IL-5-and its receptor--the role of IL-5 in the development of hematopoietic cells in the long-term bone marrow cultures]. AB - IL-5 is a T-cell-derived glycoprotein that acts on B cells and eosinophils to induce their growth and differentiation. We clarified using in vitro long-term bone marrow culture that IL-5 supports the growth and survival of Ly-1+ common progenitor cells which can differentiate into Ly-1+ B cells and Ly-1+ macrophages. The functional IL-5 receptor (IL-5R) consists of alpha and beta heterodimers. The 60 kDa alpha chain binds to IL-5 with low affinity, while the 130 kDa beta chain does not bind with IL-5 by itself, but converts low affinity IL-5R to high affinity IL-5R together with the alpha chain. The beta chain is shared with GM-CSFR and IL-3R. PMID- 1433971 TI - [The interleukin-6 signal transducer, gp130, functioning in immune, hematopoietic, and neural systems]. AB - Functional pleiotropy and redundancy are characteristic features of cytokines. To understand the signaling mechanisms of such cytokines, we have proposed a two chain interleukin-6 receptor (IL-6-R) model: IL-6 triggers the association of a ligand-binding chain (IL-6-R) and a non-binding signal transducer (gp130) to form a high-affinity receptor complex, causing transmission of the signal by the cytoplasmic portion of gp130. This model would explain the functional redundancy of cytokines if we were to assume that gp130 interacts with several different receptor chains. Here we present data indicating that gp130 functions as a common signal transducer for IL-6, oncostatin M (OM), leukemia inhibitory factor (LIF), and ciliary neurotrophic factor (CNTF). We show that anti-gp130 monoclonal antibodies completely block the biological responses induced by all of these factors. Since LIF functions as a cholinergic differentiation factor in nerve cells as does CNTF, these results suggest that gp130 may also play a role in the neural system. PMID- 1433972 TI - [Molecular aspects of IL-7-IL-7 receptor system]. AB - IL-7 is a multifunctional cytokine which acts on cells such as B cells, T cells and macrophages. As the IL-7 clearly plays many important roles the in control of growth and differentiation, it is important to understand how IL-7 and IL-7 receptor (IL-7R) are expressed. Recently, to understand the transcriptional regulation of IL-7 and IL-7R genes, a detailed analysis of the 5' flanking region of the IL-7 and IL-7R genes has been done. In this review recent progress on these topics is introduced and discussed. PMID- 1433973 TI - [Function, molecular structure and gene expression of IL-8]. AB - Interleukin-8 (IL-8) is a potent chemotactic factor for neutrophils and T lymphocytes. Various reagents such as lectins, mitogens, IL-1, TNF, induce IL-8 production in a wide range of cells and tissues. The IL-8 gene is known to be activated by AP-1, NF-kB like factor and C/EBP like factor, but the relative importance of these transcriptional factors varies from cell to cell. Two types of human IL-8 receptor cDNA have recently been cloned. Both are G-protein coupled receptors and the amino acid sequences are highly homologous. Other members of the IL-8 family, such as GRO/MGSA and MIP2, bind to IL-8 receptors, and the receptors of other chemoattractants such as fMLP and C5a, show high homology to the IL-8 receptors. PMID- 1433974 TI - [Function, molecular structure and gene expression regulation of interleukin 9 (IL-9)]. AB - Interleukin-9 (IL-9)/P40 is a recently reported murine growth factor for helper T cell clones. It is produced by ConA stimulated CD4+ T-cells or several T-cell lines such as TUC 2.15 derived from C57Bl/6 mouse. In the murine system, IL-9/P40 directly supported proliferation of mucosal type mast cells, and also induced erythroid burst formation, indirectly. On the other hand, human IL-9, which is a homologue to murine P40, was cloned from a cDNA library prepared with mRNA isolated from PHA-induced T-cell line (C5MJ2). Analysis of the sequence of cDNA revealed a striking similarity between murine and human IL-9/P40. Human IL-9 supported formation of a subpopulation of erythroid bursts that are responsive to IL-3. In this communication, identification, cloning of cDNA, and biological activities of murine and human IL-9/P40 are discussed. PMID- 1433975 TI - [Function, molecular structure and gene expression regulation of interleukin-10 (IL-10)]. AB - Interleukin-10 has a variety of biological activities. Murine interleukin-10 inhibits cytokine production by Th2 cells in the presence of macrophages, enhances T cell proliferation, sustains the viability of B cells in vitro, induces class II MHC antigen expression on B cells, enhances mast cell proliferation in the presence of IL-3 and/or IL-4, and inhibits cytokine production by macrophages. Human interleukin-10 inhibits cytokine production by human T cells and reduces antigen-specific human T cell proliferation by downregulation of class II MHC antigen expression on monocytes. cDNA clones encoding murine and human interleukin-10 exhibit a strong homology to BCRFI in Epstein-Barr virus. BCRFI conserves only a part of interleukin-10 activities. PMID- 1433976 TI - [Function, molecular structure and gene expression of interleukin-11 (IL 11/AGIF)]. AB - Interleukin-11 (IL-11) is a novel cytokine that was identified in a medium conditioned by the primate bone marrow-derived stromal cell line PU-34. It was originally identified as a growth factor for the IL-6-dependent plasmacytoma cell line T1165. Adipogenesis inhibitory factor (AGIF) was cloned from the human bone marrow-derived cell line KM-102. The AGIF cDNA sequence was revealed to be identical to that of the IL-11 cDNA. AGIF inhibits the process of adipogenesis of the bone marrow-derived preadipocyte cell line H-1/A. Other biological activities of IL-11/AGIF, megakaryocytopoiesis, stem-cell proliferation, hepatic acute phase responses and antigen-specific antibody responses are also summarized. PMID- 1433977 TI - [Function,molecular structure and gene expression of macrophage colony stimulating factor]. AB - Human urinary macrophage colony-stimulating factor (hM-CSF) is a glycoprotein with a molecular weight of 85 kDa which consists of two homologous subunits with a molecular weight of 43 kDa. It stimulates monocyte production through the stimulation of progenitor cells to differentiate to mature monocytes as well as neutrophil production through the stimulation of mature monocytes to produce granulocyte-macrophage and granulocyte CSF. It also enhances platelet production through the production of megakaryocyte potentiator (Meg-POT). Recently, proteoglycan type M-CSF has been found by our group. This type of M-CSF has a molecular weight of greater than 200 kDa and consists of a 43 kDa subunit and a 150-200 kDa subunit, the latter of which contains chondroitin sulfate glycosaminoglycan. This proteoglycan type M-CSF binds to extra-cellular matrix at the part of glycosaminoglycan. In addition to hematopoiesis-stimulating activity, M-CSF has a promoting activity on monocyte tumor-killing, osteoclast production and differentiation of cytotrophoblasts to syncytiotrophoblasts which secrete gonadotropin. M-CSF receptor (M-CSF-R) was found as a product of proto-oncogene, c-fms which consists of 972 amino acids. Mutations at Tyr 969 and Ser 301 of M CSF-R has been found in patients with myelodysplastic syndrome and monocytic leukemia. PMID- 1433978 TI - [Function, molecular structure and gene expression of granulocyte-macrophage colony stimulating factor]. AB - Granulocyte-macrophage colony stimulating factor (GM-CSF), a 22 kDa glycoprotein secreted from activated T cells and stroma cells, plays an important role, both in the constructive and inducible hemopoiesis, by stimulating a wide range of hemopoietic cells. After the cloning of receptor genes, the high affinity GM-CSF receptor was reconstituted by the combination of cloned 80 kDa molecule (alpha chain) and 120 kDa molecule (beta chain). This human GM-CSF receptor beta chain also works as a beta chain of IL-3 or IL-5 high affinity receptor. The fact that the alpha chains of GM-CSF, IL-3 and IL-5 share the same beta chain may define a biological interaction among these three cytokines. PMID- 1433979 TI - [Function, molecular structure and gene expression regulation of erythropoietin]. AB - Erythropoietin (EPO) is a glycoprotein hormone which enhances red blood cell production by stimulating growth and differentiation of erythroid progenitor cells. Recombinant human EPO (huEPO), expressed in CHO cells, is highly similar to urinary huEPO with respect to both structural and functional properties. EPO production is primarily localized to peritubular interstitial cells in the cortex of the kidney. Increased EPO production due to anemia seems to be correlated with increased numbers of EPO-producing cells rather than with increased production by the individual EPO-producing cells. A heme protein is proposed to be the oxygen sensor. Tissue-specific and hypoxia-inducible expression of EPO gene is governed by multiple regulatory elements. Murine CFU-E from the spleens of mice, infected with the anemia-inducing strain of Friend virus, differentiate into reticulocytes in response to EPO. EPO appears to prevent CFU-E from programmed death (apoptosis). The gene for mouse EPO receptor produces 65 Kd protein on the cell surface. This protein seems to be specifically associated with another 100 Kd and/or 85 Kd proteins. The gene for human EPO receptor was also cloned, based on its similarity to murine counterpart. EPO receptor belongs to a novel class of receptors termed the cytokine receptor superfamily. PMID- 1433980 TI - [Epidermal growth factor and its receptor: the structure and function]. AB - Epidermal growth factor (EGF) binds to the specific membrane receptor and subsequently activates the signal transduction pathway through intrinsic tyrosine kinase activity. To elucidate the mechanism in which structural alteration of the EGF may affect functional properties including its receptor binding ability, site directed mutagenesis has been employed. The functional significance of structural characteristics of the EGF receptor has been studied also by mutant receptor constructs in the transfected cells. Recent progress on the studies of the EGF and EGF receptor interaction are reviewed. PMID- 1433981 TI - [Function, molecular structure and gene expression of fibroblast growth factor (FGF/HBGF)]. AB - The structure and function of members of the fibroblast growth factor (FGF) gene family and their receptors are reviewed. All the member of this gene family bind heparin, and therefore, are also called the as heparin-binding growth factor (HBGF). In this review, the structural features of FGF/HBGF are summarized first, and general features of the structure and function of their receptors are then described briefly. After biological effects of FGF/HBGF on adult-type tissues and cultured cells are reviewed, effects of FGF on the mesodermal induction in amphibian (Xenopus laevis) embryonic system are reviewed in more detail. Emphasis is given on the experiments with Xenopus animal cap assay system and also on the injection into Xenopus fertilized eggs of mRNA of dominant defect mutant of FGF receptor, which leads to the formation of embryos with abnormal axial mesoderm. PMID- 1433982 TI - [Function, molecular structure and gene expression regulation of Platelet-derived growth factor]. AB - Platelet-derived growth factor (PDGF) is a cationic glycoprotein of approximately 30 kDa, composed of two subunits. These subunit chains are termed A (18 kDa) and B (12-14 kDa) with high homology of the peptide sequences, including 8 cysteine residues at identical positions. Three isoforms of PDGF, AA, BB homodimers and AB heterodimer are distributed in the different tissues and cell lines suggesting that these isoforms have different functions. Two types of PDGF receptors alpha, and beta with Mr of 160-180 kDa are seen on the cell surface. PDGFR alpha can bind to both A and B subunits of the PDGD, while PDGFR beta, only B subunit. PDGF (AA) combines alpha alpha, PDGF (AB) makes dimers of alpha alpha and alpha beta, and PDGF (BB) can make three types of dimers, alpha alpha, alpha beta, and beta beta. These dimeric PDGFRs are active forms and phosphorylate its own domain and other neighbor specific proteins. The substrates of the receptor kinase are phospholipase C-gamma, GTPase activating protein (GAP), serine/threonine kinase Raf-1 and others. These molecules are thought to transfer information of the PDGFs on its receptors to the nucleus. PMID- 1433984 TI - [Function, molecular structure and gene expression of insulin-like growth factors ]. AB - In this short review, gene structure, transcriptional pattern, biological activity, specific receptors and binding proteins for insulin-like growth factors (IGF: IGF I and IGF II) are explained. In spite of their close similarity in both gene and peptide structures, their receptors are completely distinct from each other in molecular structure and in signal transduction. Expression of IGF function in vivo is strongly restricted by plasma binding proteins. PMID- 1433983 TI - [Function, molecular structure and gene expression regulation of nerve growth factor]. AB - Nerve growth factor (NGF) is the initially discovered and best characterized target-derived neurotrophic factor. The NGF gene family includes NGF, brain derived neurotrophic factor (BDNF), neurotrophin (NT)-3, NT-4, and NT-5. The members of this family can interact with the members of trk family of receptor like protein-tyrosine kinases (trk, trk B and trk C), suggesting that the different trk protein serves as receptor subunits for the different neurotrophins. Meanwhile, some recent reports have shown that exogenous administration of NGF itself or a stimulator of NGF synthesis to damaged neurons have beneficial effects. These findings open the possibility of new therapy for nervous diseases, such as Alzheimer's disease. PMID- 1433985 TI - [Function, molecular structure and gene expression regulation of transforming growth factor-beta (TGF-beta)]. AB - Transforming growth factor-beta (TGF-beta) is a multifunctional peptide growth factor widely distributed in vertebrates and represents a prototype of a large family of structurally related factors that regulate various cellular functions, ranging from amphibian embryonal development to hormone production in the human pituitary. TGF-beta is a disulfide-bonded homodimer of a subunit of 12.5 kD that is derived from a much larger precursor. The amino acid sequences of TGF-betas are highly conserved among species, suggesting their physiological importance. TGF-beta was originally isolated from human platelets as a factor that induces anchorage-independent growth of normal fibroblasts. However, later studies have revealed that its major biological activities include inhibition of cell proliferation, and regulation of differentiation, cell adhesion and extracellular matrix deposition. There are three types of cellular receptors that bind TGF beta. Type II receptor, of which cDNA was recently cloned, is a functional serine/threonine kinase and is thought to be involved in the TGF-beta-mediated signal transduction pathway. The importance of TGF-beta in clinical medicine will increase not only as it is a promising therapeutic drug, but also as its excessive activity can be the cause of various human fibrotic diseases. PMID- 1433987 TI - [Function, molecular structure and gene expression regulation of receptor for D factor/LIF]. AB - Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor (LIF) is a cytokine inducing differentiation of mouse myeloid leukemic M1 cells. IL-6, oncostatin M (OSM) and G-CSF also induce differentiation of M1 cells. These four cytokines are suggested to be members of a single cytokine family. The LIF receptor is structurally related to the gp130 signal-transducing component of the IL-6 receptor and to the G-CSF receptor. The high-affinity receptors for LIF, OSM and IL-6 share the common subunit, gp130. This provides an explanation for the functional redundancy of those cytokines. PMID- 1433986 TI - [Function, molecular structure and gene expression regulation of LD78]. AB - LD78 is a member of a new cytokine superfamily, consisting of at least twelve small proteins, which are involved in inflammation and cell growth. Depending on their primary structure, these cytokines can be divided into two families, one of which contains LD78 and is known as the CC family. The protein and gene structures and the physiological functions of LD78 in comparison with the other CC family members are summarized here. Furthermore, the generation mechanism of the three LD78 genes and their expression are discussed. PMID- 1433988 TI - [Structure and biological property of fibroblast-derived tumor cytotoxic factor (F-TCF)]. AB - Fibroblast-derived tumor cytotoxic factor (F-TCF), isolated from human embryonic lung fibroblasts, is cytotoxic against various human and mouse tumor cells. Physicochemical and biological properties indicate that F-TCF is closely similar to hepatocyte growth factors (HGFs), cDNAs of which are isolated from human liver and placenta. Isolation and expression of F-TCF cDNA revealed that F-TCF was identical to the placenta type HGFs, including a variant with a deletion of 15 base pairs in the coding region. The deleted form of recombinant HGF (rHGF) had slightly lower heparin binding affinity than the intact form. Specific activities of rHGFs were almost the same in tumor cytotoxic activity, but different in hepatocyte growth stimulating activity. These results indicate that deletion of five amino acids results in conformational change which alter biological activity. PMID- 1433989 TI - [Therapy with interleukin 2 for chronic viral hepatitis]. AB - We administered 250-10,000 u of recombinant interleukin 2 (r-IL2) for 1-4 weeks intravenously or intramuscularly to patients with chronic hepatitis B positive for serum HBe antigen as immunostimulants and studied the effect of r-IL2 for antiviral system. Serum ALT levels increased during the therapy and then decreased after the treatment. Activities of DNA-P were gradually reduced and became negative in 6 of 11 cases. Serum HBeAg decreased and anti-HBe increased during and after the therapy. Peripheral lymphocytes and eosinocytes increased during the therapy but returned to the pretreatment level after the therapy. TSI (%) increased rapidly and TS (%) decreased during infusion of r-IL2. However, TH/TS ratio increased after the infusion since TH (%) decreased gradually during the infusion of r-IL2. The r-IL2 therapy was useful for chronic hepatitis with serum HBe antigen as therapy with immunostimulant or treatment with biological response modifier (BRM). PMID- 1433990 TI - [Acid-base regulation: a general introduction]. AB - Acid-base homeostasis of the body fluid in all the animal species including humans is now recognized to be kept at 0.6-0.7 unit higher than neutral pH (pN). This concept is called relative constant alkalinity. It has also found that intracellular pH is approximately kept at pN, so that the difference between extracellular (pHo) and intracellular pH (pHi) is again 0.6-0.7. Since pN increases about 0.016 unit/1 degree C with decreasing temperature, normal blood pH at 20 degrees C is about 7.7 in cold-blooded animals as well as in humans with low temperature e.g. during special operative procedure. The main physiological significance for maintaining pHi at pN is that ionized small molecules in the cell are held within the intracellular space and metabolic process can be proceeded smoothly. PMID- 1433991 TI - [General aspect of cellular pH regulation]. PMID- 1433992 TI - [Measurement of intracellular pH]. AB - Since various cellular processes depend on changes in pH, the regulation of intracellular pH (pHi) is important both for the individual cell and for the organism. The mechanisms of the regulation of pHi can be investigated by monitoring pHi. In this report, we discuss the four major techniques available for measuring pHi, which are 1) Distribution of weak acids and bases, 2) pH sensitive microelectrodes, 3) pH-sensitive dyes, and 4) Nuclear magnetic resonance. Among four techniques, the advantage of the microelectrode approach is that it can monitor membrane potential at the same time and be applied to a single cell. The dye technique is a relative new developing technique, which has lots of advantages. It is easy to use, and is capable of monitoring rapid pHi changes, and being applied to a smaller cell, or a single cell. PMID- 1433993 TI - [Band 3 protein, anion exchange protein of the erythrocyte membrane]. AB - Band 3 protein is the major transmembrane protein of the erythrocyte membrane, comprising 25% of the total membrane protein and existing at 10(6) copies per cell, and mediates the rapid exchange of anions across the membrane. The exchange of Cl- for HCO3- anions plays an important role on the regulation of oxygen and bicarbonate delivary to or from peripheral tissues. Band 3 protein has functionally distinct two domains. The membrane-spanning domain, 55K domain, is believed to span the membrane bilayer 14 times and mediates the rapid anion exchange. The complementary cytosolic domain, 40K domain, is an anchor for the cytoskeletal proteins and regulates the cell deformability and the cell life span. The purpose of this paper is to review the physiological functions of band 3 protein and the anion exchange mechanisms. PMID- 1433994 TI - [Respiratory regulation system]. AB - In 1874, Kussmaul described "featiful terminal dyspnea" in a case of severe diabetic coma. Probably, this was the first sign of respiratory regulation for metabolic acidosis. After this first case, about 40 years has been needed to establish the theory of acid-base equiribration, namely Henderson-Hasselbalch's equation. pH = 6.1 + log [HCO3-]/[H2CO3] This equation indicates that plasma pH is determined by the ratio of HCO3 concentration and H2CO3 concentration. Because of linear relationship between H2CO3 and PaCO2, pH depend on the ratio of HCO3- and PaCO2. In the state of metabolic acidosis, increase of [H+] stimulates ventilation and decreases the PaCO2. Inversely, in the state of metabolic alkalosis, increase of PaCO2 occurs. These reactions are called "respiratory compensation" or "respiratory regulation". The respiratory regulation system will not retern pH to normal (7.4), but compensation has some limitation which is shown as "SIGNIFICANCE BAND". In this paper, physiological and clinical importance of respiratory regulation and significance band is discussed. PMID- 1433995 TI - [Acid-base equilibrium control system--red cell function]. AB - The physiological functions of the red cell are oxygen transport, facilitation of carbon dioxide transport and control of acid-base equilibrium in the blood. The last function is closely related to the first two, which are cooperative to each other. The oxygen transport by red cells is characterized by high efficiency and regulation, which depend on allosteric properties of hemoglobin. The CO2 transport in the form of bicarbonate is also facilitated by the buffer action and the Haldane effect of hemoglobin. Hemoglobin is the major buffer system in the red cell. Its buffer power is strengthen through the Haldane effect. Carbonic anhydrase in red cell, together with band 3 protein in the membrane which facilitates the Cl-/HCO3- exchange across membrane, allows the conversion between CO2 and HCO3- and the buffering of carbonic acid to occur in a time scale of blood circulation. PMID- 1433996 TI - [Urinary acidification]. AB - Current understanding of the features and mechanisms of renal acidification along the nephron segments is summarized. Emphasis is placed on recent approaches to the "structure and function" of H/HCO3 transport proteins by molecular techniques. The amount of renal acidification is strictly matched to the endogenous production of non-volantile acids. This regulation is handled by many factors, including blood acid-base parameters, aldosteron, distal delivery of Na and accompanying anions, extracellular fluid volume, and PTH. Cellular mechanisms of these regulatory factors are summarized. PMID- 1433997 TI - [The interaction between neural activity and intracellular pH]. AB - The regulation of intracellular pH (pH(i)) in the nervous system has been vigorously studied using a variety of animal cells in the last decade, through advances in techniques for measuring pH(i) accurately in living cells. These studies have elucidated the mechanisms of pH(i) regulation, such as intracellular buffering and acid transport across the cell membrane, in neurons and glial cells. Following an outline of pH(i) regulation, the interaction between neural activity and acid-base balance is discussed. The dynamic change of pH(i), produced by neural activity, and the effect of pH(i) on the electrical properties of neurons and other excitable cells is emphasized. PMID- 1433998 TI - [Acid-base balance and contraction of the cardiac muscle]. AB - In cardiac muscle, intracelular pH (pHi) is regulated to close to 7.1, both by membrane transport systems (Na-H and Cl-HCO3 exchange) and intracellular H+ buffers. Internal acidosis depresses the contraction, while alkalosis increases it. Internal proton depresses the contraction even without altering the internal concentration of Ca (Cai). The proton blocks the Ca channels. However, as it releases membrane-bound Ca and the influx of Na via Na-H exchange increases Ca influx through Na-Ca exchange, pHi decrease is often accompanied by the Cai increases. The internal proton also affects the uptake and release of sarcoplasmic reticulum, Ca binding to troponin, actomyosin dynamics and variable catalytic processes. PMID- 1433999 TI - [Effects of pH on vascular smooth muscle contraction]. AB - Effects of pH on vascular smooth muscle contractility were reviewed. Basic effect of acidosis seems to be the inhibition of K channels and L-type Ca channels. Inhibition of K channels results in a membrane depolarization, opening of L-type Ca channels, increase in Ca influx and muscle contraction. Inhibition of Ca channels results in an opposit effect. Thus, the effect of acidosis is determined by the relative potency of these two contradictory effects. This may be the reason why acidosis induces contraction in polarized muscle whereas it slightly inhibits contraction in depolarized muscle. In addition, measurements of cytosolic Ca level simultaneously with muscle tension suggest that acidosis increases Ca sensitivity of contractile elements, and this effect also helps acidosis to induce contraction in vascular smooth muscle. PMID- 1434000 TI - [Effect of pH on blood cells]. AB - Intracellular pH of blood cells is controlled by the Na+/H+ exchanger and anion channels. The Na+/H+ exchanger plays a major role in elevating intracellular pH in activated platelets, lymphocytes and neutrophils. In lymphocytes, intracellular alkalinization is associated with proliferation and differentiation. In platelets, protein kinase appears to increase the turnover rate of Na+/H+ exchange, thus accelerating the process of alkalinization. Intracellular alkalinization serves to increase the energy supply by glycolysis, and to activate the production of thromboxane A2, a potent activator of platelets. Clinically an increased activity of the Na+/H+ exchanger has been demonstrated with platelets from hypertensive patients. PMID- 1434001 TI - [Renal adaptations to acid-base disorders]. AB - Alterations in acid-base status affect renal hemodynamics and tubular function. GFR is reduced both in acute acidosis and alkalosis. Tubular functional adaptation to acute acidosis includes an acceleration in proximal acidification, induced by the increase in Pco2 and luminal bicarbonate concentration and a stimulated ammonia production, induced by low pH. Alteration in distal bicarbonate reabsorption is also an important determinant of the net acid excretion. Renal functional alterations in acute alkalosis include a reduction in GFR and a stimulated bicarbonate secretion in the cortical collecting duct. Proximal acidification is almost unchanged during acute alkalosis but reportedly accelerates after at least 3 weeks of maintained alkalosis. Renal adaptation during chronic phase of acid-base disorders differs from that during the acute phase. PMID- 1434002 TI - [Effects of pH on the endocrine system and metabolism]. AB - Changes in extra- and intracellular pH affect metabolic states and hormone responses. In general, alkalosis stimulates and acidosis inhibits glycolysis although the relationship is not a simple one. 6-phosphofructo-1-kinase, a rate limiting enzyme in glycolysis, seems to be activated directly by a rise in pH. Alkalosis stimulates the production of pyruvic acid and lactic acid. Citric acid cycle is stimulated in alkalosis and hexose monophosphate shunt pathway is facilitated in acidosis. Acid-base disorders affect the insulin secretion and insulin action. In acidosis, insulin action in the target tissues is reduced. Other hormones, including parathormone, renin-angiotensin-aldosterone system, and adrenocorticotropine, respond to the changes in pH. PMID- 1434003 TI - [Clinical aspects of acid-base disorders]. AB - Acid-base disorders are frequently recognized in a wide variety of clinical settings such as severe systemic hospitalized patients. The principal object is to assessment of acid-base equilibrium and to obtain an appropriate guide to therapy. The approach is centered to a systemic analysis of blood gas evaluation. To establish this complex matter is followed. Is an acid-base disorder present? Is the disorder a simple or a mixed abnormality? What is the primary cause? These evaluations should be obtained by accurate history taking, physical examination, and routine laboratory tests. In addition, the supporting analysises such as anion gap (AG) calculation, urine AG assessment, urine chloride concentration and so on are also useful for correct diagnosis. In view of the complexty and difficult expression of acid-base disorders, it is desirable that clinicians must have full knowledges of systemic approach to the blood gas analysis and its evaluation. PMID- 1434004 TI - [Diagnosis, countermeasure and classification of acidosis]. AB - Acidosis is the result of the net addition of hydrogen ion to the extracellular space or loss of bicarbonate from that space. Hydrogen ion may be added by the increased production of strong acids, an increase in CO2 concentration, or the addition of exogenous acids. The common approach to the differential diagnosis of metabolic acidosis is to divide the patients into two categories based on whether the anion gap in plasma is increased or not. Metabolic acidosis with normal anion gap (hyperchloremic) suggests that bicarbonate has been effectively replaced by chloride. In contrast, metabolic acidosis with an increased anion gap suggests addition to the body fluids of an acid other than hydrochloric acids or its equivalent. PMID- 1434005 TI - [Diagnosis, therapy and classification of alkalosis]. AB - The pathogenesis, classification, diagnosis and treatment of alkalosis are described. Alkalemia is defined as an elevation in the blood pH and alkalosis refers to processes that tend to raise the pH, and divided into two types; metabolic alkalosis (a primary increase in plasma HCO3- concentration) and respiratory alkalosis (a primary decrease in PCO2). These disorders are most frequently observed in the hospitalized patients. As the critically ill-patients with severe alkalemia are often associated with high mortality, treatment should be directed to the underlying diseases and severe alkalemia should be corrected promptly. PMID- 1434006 TI - [Mixed acid-base disorders]. AB - Maintenance of the acid-base balance is critical for keeping cellular and whole body integrity, and acid-base disturbances are commonly encountered in critically ill patients. In this chapter, the classification and the pathogenesis of mixed acid-base disorders are reviewed in order to understand and manage these abnormalities. First of all, the compensatory reactions to the primary acid-base state must be evaluated. Careful examination of the physical findings and medical history are also essential for making a correct diagnosis and to treat the patients effectively. PMID- 1434007 TI - [Graphic evaluation of the significance band for hypercapnia in pulmonary disorders]. AB - Alveolar hypoventilation due to the chronic obstruction of the airway such as pulmonary emphysema, or severe restrictive dysfunction due to sequela of pulmonary tuberculosis causes chronic hypercapnia (chronic respiratory acidosis). Ninety-five percentile of significance band of chronic and acute hypercapnia of both experimental and clinical setting is introduced in the graphic display of the acid-base balance. On acute exacerbation of these disorders, examination of arterial blood gas in series are usually plotted along the significance band of hypercapnia. With clinical improvement, the plot will gradually drop down to the chronic stable area of the band. Although cases with metabolic disorders complicate the interpretation, evaluation of the acid-base status using the graphic display will be of help at bedside assessment. PMID- 1434008 TI - [Acid-base disturbances in heart failure]. AB - Disturbance in acid-base balance is commonly observed in patients with heart failure. The most common disturbance is metabolic alkalosis combined with hypokalemia, as a result of the excessive use of loop diuretics. Occasionary, hypoxia due to pulmonary edema stimulates ventilation, resulting in respiratory alkalosis. When pulmonary edema develops, carbon dioxide retention occurs, resulting in respiratory acidosis. Decreased tissue oxygen delivery may also produce lethal lactic acidosis. Compensatory mechanisms, coexistence of independent acid-base disorders and changes in electrolytes complicate acid-base balance in the individual patients. As acid-base disturbances have harmful effects on the cardiovascular system, precise diagnosis and proper treatment are highly important. PMID- 1434009 TI - [Impairment of acid-base balance in renal failure]. AB - It is very critical for the living organism to maintain homeostasis of body fluid volume and its electrolyte composition by renal regulation, including acid-base balance. In renal failure, impaired acid-base balance is inescapable because of disturbed urinary acidification, one of the major renal functions. Among all types of acid-base imbalance, metabolic acidosis is a major one in renal failure. For better understanding of this issue, several fundamental items for the renal mechanisms of urinary acidification must be discussed first, and the pathophysiological features and their relevant treatment for acid-base imbalances in renal failure, next. Moreover, some comments on the practical aspects, in long term dialyze uremic patients, is also provided. PMID- 1434010 TI - [Disorders of acid-base balance in liver disease]. AB - Disorders of acid-base balance are frequently encountered in fulminant hepatic failure, liver cirrhosis and autoimmune liver diseases. The disorders per se except lactic acidosis rarely poses serious clinical problems. However metabolic alkalosis induced by administration of diuretics and hypokalemia in renal tubular acidosis are risk factors for hepatic encephalopathy. PMID- 1434011 TI - [Acid-base disturbance in adrenal and parathyroid diseases]. AB - Aldosterone stimulates sodium absorption in the collecting tubule, which makes the potential more lumen-negative, and secondarily stimulates proton and potassium secretion. Potassium depletion stimulates ammonia synthesis, which increases distal buffer delivery, increases luminal pH in the collecting tubule, and secondarily stimulates proton secretion. This stimulation of the distal nephron acidification by aldosterone can result in metabolic alkalosis. Inversely, aldosterone deficiency can produce characteristic metabolic acidosis with hyperkalemia (type IV renal tubular acidosis). Acute administration of parathyroidhormone (PTH) decreases renal bicarbonate reabsorption in the proximal tubule. Since the effect of PTH is overridden by other factors, such as PTH induced base release from bone, hyperparathyroidism does not uniformly cause metabolic acidosis. PMID- 1434012 TI - [Renal tubular acidosis]. AB - Renal tubular acidosis (RTA) can be separated into three main types: distal RTA (the defect in the excretion of hydrogen ion), proximal RTA (the defect in the reabsorption of bicarbonate), and hyperkalemic RTA. Some patients present combined types of proximal and distal RTA. Most of the pediatric patients with RTA manifest failure to thrive. They have hyperchloremic metabolic acidosis and normal plasma anion gap. Fractional excretion of bicarbonate is below 5% in dRTA and over 15% in pRTA. Renal complications of dRTA are nephrocalcinosis, renal calculi, renal cysts and reversible low molecular weight proteinuria. The patient with isolated pRTA is very rare. PMID- 1434013 TI - [Acid-base balance disorder in various diseases--diabetes mellitus]. AB - Metabolic acidosis is the serious acid-base balance disorder complicated in diabetes mellitus. The pathogenesis and treatment of various type of metabolic acidosis (Keto-acidosis, lactic acidosis, hyperchloremic acidosis and type IV renal tubular acidosis) are discussed. Metabolic acidosis in the diabetic patient is associated with an increased anion-gap caused by the presence of organic anion (beta-hydroxybutyrate, acetoacetate, and lactate). The rise in anion-gap usually equals the fall in plasma bicarbonate. With appropriate therapy, progressive decline in the anion-gap is one of the best indications of successful treatment. If hyperchloremic acidosis is established, appropriate infusion of hypochloremic rehydration fluid may be useful. PMID- 1434014 TI - [Acid-base disturbances in hematologic diseases]. AB - In this article, the acid-base disturbances encountered in hematologic diseases are discussed. Occurrence of lactic acidosis (LA) without obvious clinical tissue hypoxia has been reported in patients with leukemia and lymphoma. Most of the patients with LA had liver involvement and clinical evidence of impaired hepatic function, suggesting that both increased production and decreased lactate metabolism are necessary for the development of LA in leukemia and lymphoma. Acute tumor lysis syndrome consists of hyperuricemia, hyperpotassemia, and hyperphosphatemia with hypocalcemia following neoplastic cell lysis, particularly in lymphoproliferative disorders. In patients with multiple myeloma (MM), proximal renal tubular acidosis (Fanconi syndrome) associated with Bence Jones proteinuria has been reported. In addition, MM is one of the first conditions recognized to be associated with lower anion gap. PMID- 1434015 TI - [Lactic acidosis]. PMID- 1434016 TI - [Acid-base disorders in anesthesiology and in related fields]. AB - Acid-Base disorders in anesthesia and in related fields were discussed. Four topics were chosen because they are relatively new and attracting attentions. They are 1) Monitoring Petco2 in anesthesia and in Intensive Care, 2) Relationships between newly established laparoscopic surgery and ventilatory impairment/elevation of Paco2, 3) Surgery in which large amount of chloride ion is absorbed, and 4) High venous Pco2 in resuscitation. PMID- 1434017 TI - [Drug-induced acid-base disorders]. AB - Drug-induced acid-base disorders may be classified into four categories with respect to the mechanism. 1. Metabolic acidosis is induced by a large acid loads incurred from exogenous sources (e.g. NH4Cl, or toxin ingestion) or endogenous acid production (e.g. generation of ketoacids or lactic acids by alcohol or phenformin) or base loss (e.g. abuse of laxatives). 2. Metabolic alkalosis results from exogenous bicarbonate loads (e.g. milk-alkali syndrome) or effective extracellular fluid contraction, potassium depletion plus hyperaldosteronism (e.g. vomiting, diuretics, or licorice). 3. Renal tubular acidosis is induced by the drugs which mainly impair proximal and/or distal tubules (e.g. vitamin D, NSAID, acetazolamide or amphotericin B). 4. Respiratory acidosis or alkalosis results from drug-induced respiratory center depression or neuromuscular impairment (e.g. anesthetic, sedative overdosage or curare) or hyperventilation (salicylates, paraldehyde, epinephrine, or nicotine). PMID- 1434018 TI - [Acid-base disturbances in surgical operation]. AB - Metabolic acidosis immediately after surgical operation is followed by metabolic alkalosis. Hormonal change by surgical stress and anaerobic glucolysis due to tissue ischemia cause initial lactic acidosis. Later alkalosis may be caused by secondary aldosteronism and bicarbonate production from lactate and citrate supplied by massive infusion and transfusion. Postoperative complications, such as respiratory insufficiency, renal failure and hypovolemic or septic shock, cause acidosis. In the gastrointestinal surgery, acidosis can be caused by starvation and loss of bicarbonate contained in bile, pancreatic juice or intestinal fluid, and alkalosis can be caused by loss of HCl in gastric juice. Severe acidosis can be caused by extracorporeal circulation, hypothermia, low output syndrome or declamping shock in cardioaortic surgery. PMID- 1434019 TI - [Acid-base disturbances in pediatrics]. AB - Acid-base balance is regulated by respiratory and metabolic factors and also by the compensatory mechanisms of the body. This balance is often disturbed by various diseases or conditions in children. These diseases or conditions which cause acidosis or alkalosis in pediatric practice are presented and discussed in this paper with special interest in their age at presentation. PMID- 1434020 TI - [Abnormalities in acid-base balance in the elderly]. AB - Physiological decline in the ability to adjust acid-base balance and increase the incidence of diseases with aging, modifies pathophysiological and clinical features of acid-base disturbance in the elderly. Regulation of pH ultimately depends on the kidney and lung, however, the ability of the two organs is decreased with physiological aging. Moreover, the elderly are more prone to suffer from renal insufficiency and/or chronic obstructive pulmonary disease. Furthermore, medication with various drugs, such as diuretics, often affect the acid-base balance in the elderly. This paper describes the characteristics of the abnormalities in acid-base balance in the elderly, including metabolic acidosis and alkalosis, and respiratory acidosis and alkalosis. PMID- 1434021 TI - [Acid-base balance during exercise]. AB - The required energy may be produced almost exclusively by aerobic processes during light exercise. Anaerobic energy-yielding metabolic processes however, play a greater role as the severity of the exercise increases. This process produces endoproducts, such as lactate, which are related to acid-base regulation. During exhaustive exercise, large amounts of lactate accumulate in both muscle and blood, and the corresponding accumulation of proton ions produces metabolic acidosis. Three mechanisms control the acid-base quality of the internal environment; intramuscle buffers, blood buffers and physiologic buffers. In healthy male, the change in blood pH after heavy exercise is one which is expected in conditions of metabolic acidosis, and this change is consistently related to the lactate content. Finally, the effect of exercise on acid-base status in patients with several conditions is discussed. PMID- 1434022 TI - [Transgenic mouse and gene targeting]. AB - Transgenic mouse technology has proved to be a powerful tool for medical research. So far, a large number of transgenic mice have been generated expressing, e.g. oncogenes, viral genes, immunoglobulins, lymphokines and MHC antigens, and have provided much valuable information. Furthermore, gene targeting technology (homologous recombination between specific chromosomal DNA sequences and exogenously introduced DNA sequences) has been improved and applied to pluripotent, mouse embryonic stem (ES) cells, providing the means to create mice of specifically altered genotype. In this review, some of the background and recent advances of transgenic mouse technology and gene targeting in mouse ES cells are described. PMID- 1434023 TI - [Mutations of amyloid precursor protein in early-onset familial Alzheimer's disease]. AB - Genetic linkage studies of familial Alzheimer's disease (FAD) have suggested that some form of early-onset FAD is linked to proximal long arm of chromosome 21. It has been also suggested that some form of late-onset FAD is linked to long arm of chromosome 19. Goate et al have identified a mis-sense mutation (Val to Ile) in exon 17 of the amyloid precursor protein (APP) gene in 2 of 16 early-onset FAD families, and have shown that the FAD locus in an FAD family is tightly linked to the mis-sense mutation. To determine if the mis-sense mutation is observed in different ethnic origine, we have studied some early-onset FAD families. Two early-onset FAD families showed the existence of the mutation. As the mutation has been identified in different ethnic origine and the mutation has not been observed in normal individuals, it strengthen hypothesis that the mutation is pathogenic. Recently, Val to Phe and Val to Gly mutations have been also identified at the same codon (Codon 717) of the APP gene. PMID- 1434024 TI - [Acid base balance in the digestive system]. AB - The mechanisms of acid base balance in digestive organs, including stomach, intestine as well as liver, have been described in the present paper. The stomach secrets large amount of acid as well as sodium bicarbonate, so that hydrogen ion would be lost in the severe vomiting state such as pyloric stenosis, resulting in metabolic alkalosis and hypokalemia. In the diarrheal condition, sodium bicarbonate would be lost in large amount, causing metabolic acidosis and hypokalemia. Hepatic failure induces the respiratory alkalosis of which mechanisms have not been clarified yet. In any case, urgent correction of acid base imbalnce would be crucial. It is, however, obscure to date how the systemic acid base imbalnce affects the function of the digestive system. This issue would be promising field in the investigation of digestive diseases. PMID- 1434025 TI - Dysplasia in the human esophagus: clinicopathological study on 500 esophagi at autopsy. AB - To clarify the relation between esophageal carcinoma and dysplasia, the pathology and epidemiology of 500 cases where clinically overt esophageal carcinoma had not been the direct cause of death were studied at autopsy. There were 297 men and 203 women. Four hundred and eighty-five patients had had malignant disease, of which 91 fulfilled the criteria for multiple primary malignancies. For all cases, cigarette and drinking habits were examined in patient records. All the esophagi were examined at autopsy by microscopy. Carcinoma in situ was found in six cases (1.2%). Dysplasia was observed in 73 (14.6%) and was graded mild in 58, moderate in 25 and severe in seven. The incidence of dysplasia was frequent in men than in women. Carcinoma in situ and severe dysplasia were more frequent where there was a history of habitual smoking and drinking, and were often associated with multiple primary cancers, mainly in the head and neck region. Predisposing factors for high grade dysplasia of the esophagus are gender, smoking, drinking, head and neck cancer and multiple primary cancers, corresponding to those of clinical esophageal carcinoma. PMID- 1434026 TI - The role of socioeconomic factors in the survival of patients with gastrointestinal cancers. AB - The relations between type of occupation, marital status and residential area and survival from gastrointestinal cancers were examined among 4485 cases of stomach cancer and 2618 cases of colorectal cancer diagnosed between 1983 and 1988 and recorded in the Aichi Cancer Registry. In univariate analyses, the cumulative five-year survival rates of both cancers were highest among professionals and managers and lowest among service workers, in males. They were highest among professionals, managers and clerical workers and lowest among housewives, in females. For both men and women, single people had a lower survival rate than married, and patients living in a metropolis had a higher survival rate than those living in other areas. Multivariate analyses, based on Cox's proportional hazards model, revealed occupation to have a statistically significant effect on prognosis for both sexes, although the effect of extent of disease was definitive. The analyses also confirmed the unfavorable effect of a single marital status and the favorable effect of residing in a metropolis, in women. The results suggest that socioeconomic factors may have a role to play in the survival of patients with gastrointestinal cancers. PMID- 1434027 TI - A multi-institute case-control study on the risk factors of developing pancreatic cancer. AB - A multi-institute, hospital-based, case-control study on pancreatic cancer was carried out to examine its association with preceding diseases, cigarette smoking, alcohol drinking and dietary factors. Analyses were based on 124 newly diagnosed exocrine pancreatic cancer cases and sex-, age- and institute-matched hospital controls in seven hospitals in Japan. Cigarette smoking showed a positive association with the risk of developing pancreatic cancer. Especially among smokers, a risk enhancing effect of involuntary/passive smoking prior to twenty years of age was observed (P < 0.05). No consistent associations were found with coffee, black tea or alcohol consumption. Among dietary factors, favoring food of a salty taste and drinking green tea five cups per day or more were positively associated with the risk. Drinking milk and eating fish everyday were inversely associated with the risk. PMID- 1434028 TI - Penile metastasis from lung cancer. AB - A case of metastatic tumor of the penis from lung cancer is reported. The patient, who had received a right pneumonectomy 17 months previously for a squamous cell carcinoma of the lung, complained of urinary retention and painful erection of the penis. He underwent an emergency suprapubic cystostomy. Twenty days after the procedure, he died of disseminated lung carcinoma. The autopsy demonstrated massive metastasis to the penis from squamous cell carcinoma of the lung. Penile metastasis from lung cancer is a very rare condition and only 14 cases of this secondary carcinoma have been reported. PMID- 1434029 TI - [Analysis of circulating thyroid-stimulating activities in pregnant women with Graves' disease: differential measurement of activities induced by TSH receptor antibody and hCG]. AB - Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and this aggravation is associated with postpartum relapse of thyrotoxicosis. To examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA), is responsible for this early aggravation, the respective TSA due to TSAb or hCG were evaluated with a sensitive cAMP accumulation assay using FRTL-5 cells. TSA, which was detectable in all of 11 women in normal early pregnancy, correlated positively with serum hCG level, but was abolished completely by the pretreatment of serum samples with the solid-phase hCG antibody coupled with Sepharose-4B. Total TSA in the model samples of mixture of Graves' and pregnant sera (Gr + Preg), was reduced by the pretreatment with the solid-phase antibody, just corresponding with the reduction in hCG-induced TSA. Total TSA in early pregnant sera in 15 patients with Graves' disease, decreased significantly but was still positive even by the pretreatment with the hCG antibody. Pregnancy-associated changes in TSA was examined serially in a patient with Graves' disease, and hCG induced TSA increased predominantly along with the serum thyroid hormone in early aggravation period. These data indicate that (1) the respective TSA due to TSAb or hCG can be differentially measured by using the solid-phase hCG antibody and (2) hCG plays an important role for aggravation of Graves' thyrotoxicosis in early pregnancy. PMID- 1434030 TI - [Study for the nature of interfering substances responsible for non-specific reactive phenomena occurred occasionally in EIA determination of CA125]. AB - We studied the nature of IgM-like protein responsible for non-specific reactive phenomena occurred occasionally in EIA determination of CA125. We isolated highly purified IgM-like protein from two patients with non-specifically high CA125 serum values in affinity high performance liquid chromatography (HPLC) using anti human IgM antibody-TSKgel Tresy15PW column. The isolated IgM-like protein possessed CA125 activity determined in EIA method. SDS-PAGE profiles of this isolated IgM-like protein were compatible with that of normal human IgM, and were distinct from those of CA125 antigen. Moreover, we ruled out the possibility that the Fc region of anti-CA125 monoclonal antibody might be responsible for the non specific reactive phenomena. Thus, the data obtained from the present study indicate that the IgM-like protein is an anti-idiotypic antibody against the anti CA125 monoclonal antibody (OC125). PMID- 1434031 TI - [Detection of dystrophin with anti-peptide antibodies]. AB - The analysis of dystrophin in skeletal muscles was performed to identify Duchenne and Becker muscular dystrophy (DMD and BMD) by means of immunohistochemical stain and Western blotting with antisera against synthetic dystrophin peptides. The control muscle specimens derived from normal healthy persons, and patients without DMD and BMD revealed clearly continuous stains of dystrophin at surface membrane. A band with 400 kDa of molecular size by Western blotting was positively stained by anti-dystrophin antibodies. The muscle specimens from eleven DMD patients showed no observation both in the band on Western blotting and in the immunohistochemical staining of dystrophin on frozen-thin sections. BMD muscle specimens showed patchy and faint stains, but no detection of any band on Western blotting except a 380 kDa minor band with anti-peptide IX antibody in one patient muscle. The immunohistochemical procedure was found to be more sensitive than Western blotting for the detection of dystrophin. These results indicate that the dystrophin analysis by both methods is an useful tool for the differential diagnosis of patients with DMD and BMD. PMID- 1434032 TI - [Expansion of CD4+CD8+ T lymphocytes in the peripheral blood of a patient with pulmonary tuberculosis]. AB - We detected a high level of CD4+CD8+ double marker cells in the peripheral blood of a male patient with pulmonary tuberculosis (TB), ranging from 10% to 12%. Three color staining was useful for the further examination of surface markers of these abnormal lymphocytes. Three color staining of his CD4+CD8+ cells demonstrated that his CD4+CD8+ cells expressed CD2, CD3 and TCR alpha beta. Stimulation of his PBMC with OKT3 (or rIL-2) for 4 days resulted in the increase of up to about 50% (20%) of CD4+CD8+ cells. His PBMC had a normal proliferative response to mitogen. Although we could not evaluate the significance of the presence of an expanded CD4+CD8+ cells, it was not correlate with the disease of TB or the activity of the disease at least. PMID- 1434033 TI - [Comparison of different methods for anti-HTLV-I assay]. AB - In 130 patients, who were considered to be anti-HTLV-I positive or negative by the PA method, we compared the anti-HTLV-I detection rates and the specificity of the following three EIA methods: the Ei-test ATL and two new EIA methods using different recombinant antigens which recognize different sites. The results from the three EIA methods were consistent with the results from the PA method at a rate over 96.9%. The specificity and sensitivity of the three methods were excellent. In 8 (0.6%) of the 130 cases, however, the results from the four methods were not in agreement. All of these 8 cases had been classified (by the PA method) as weakly positive (low antibody titer). The use of the Ei-test ATL produced some false positive cases and some false negative cases (no false negative cases have been reported in tests for anti-HTLV-I antibody before). In 3 patients, the results of the two new EIA methods were not in agreement. Because all of these three patients had a low antibody titer, the discrepancy was difficult to explain based on the difference in the antigens used. Although the four methods had similar anti-HTLV-I detection rates, the results indicate a need to carefully evaluate the data in patients with low antibody titers. Therefore, it is recommended that a combination of multiple tests be used or that the results from one test be checked against those from another test. PMID- 1434034 TI - [Studies on a serum factor inhibiting lactate dehydrogenase (LDH) activity in a patient's serum]. AB - We found extremely low activity of serum lactate dehydrogenase (LDH, EC. 1.1.1.27) in a 70-year-old female patient. The decrease of LDH activity was observed when the normal serum was incubated with the patient's serum. Inhibition rate of LDH activity by the patient's serum was higher at 4 degrees C than at 37 degrees C. The patient's serum inhibited both subunits of LDH, and inhibited more strongly the M-subunit than the H-subunit LDH isoenzymes. IgG (lambda type) in the patient's serum was found to be responsible for the inhibition of LDH activity. The mechanism why IgG inhibiting LDH activity developed in the patient's serum remain undetermined. PMID- 1434035 TI - [Clinical significance of the measurement of serum pepsinogen group I and II by enzyme-linked immunosorbent assay]. AB - We have developed enzyme-linked immunosorbent assay (ELISA) for pepsinogen group I and II (PG I.II) in human serum, and clinical significance of serum pepsinogen measurement was evaluated. Serum PG I.II levels in patients with gastric and duodenal ulcer were higher than those in normal healthy subjects. On the other hand, serum PG I levels in patients with pernicious anemia were significantly low levels. In both gastric ulcer and duodenal ulcer, serum PG I.II levels at active stage were higher than healing stage. These results suggested that the measurement of PG I.II levels was useful for screening or monitoring test for the injury of gastric and duodenal mucosa. PMID- 1434036 TI - [Development of automated lactate analyzer with continuous blood sampling for monitoring blood lactate and its application for the testing of physical exercise]. AB - The anaerobic threshold is useful for estimating the intensity of physical exercise. It is shown as either an increase in blood concentrations of lactate or a disproportionate increase in ventilation. We developed a lactate analyzer based on an electroenzymatic method with a continuous blood sampling system through a double-lumen catheter. Ascorbic acid, bilirubin, hemoglobin, creatinine, uric acid, and glucose did not interfere the results. The lactate concentrations in blood samples from healthy subjects during physical exercise correlated well (r = 0.993) with results measured by the conventional enzymatic method. We measured the concentrations of blood lactate with a use of this lactate analyzer to see the anaerobic threshold in nine healthy volunteers during exercise on a treadmill with an increasing workload. The point at which lactate concentrations started to increase was detected easily. The anaerobic threshold identified as a disproportionate increase in ventilation was seen at almost the same time. We conclude that the lactate analyzer, with a continuous blood sampling system, can measure precisely concentrations of lactate in blood and can detect the anaerobic threshold during physical exercise. PMID- 1434037 TI - [Immunological detection of fecal occult blood-follow up study on patients with positive testing]. AB - To evaluate its clinical utility in the early detection of colorectal diseases, we carried out the immunological fecal occult blood test in 922 patients and monitored the clinical course of the 87 patients in whom it was positive. Thirty five (40.2%) of these patients underwent subsequent X-ray and colonoscopy, and colorectal cancer was detected in 8 (20%). Our findings confirm the clinical usefulness of this test. PMID- 1434038 TI - [Decrease of CD16 antigen density on granulocytes in chronic myeloid leukemia]. AB - We examined the fluorescence intensity of CD16 antigen, which represents the density of CD16 antigen, on granulocytes by flow cytometry in 15 healthy subjects and 15 patients with neutrophilia due to inflammatory diseases and 10 patients with chronic myeloid leukemia (CML). The fluorescence intensity of CD16 antigen was significantly lower in patients with CML than in healthy subjects and also than in patients with neutrophilia. These data indicate that 1) density of CD16 antigen on granulocytes decrease in CML, and 2) analysis on the density of granulocyte CD16 antigen is useful for differential diagnosis of CML from inflammatory diseases with neutrophilia. PMID- 1434039 TI - [A case of hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity]. AB - A 68-year-old male patient with benign hypertension shows high levels of high density lipoprotein cholesterol (HDL-C) of 171 mg/dl. The serum total cholesterol was 240 mg/dl. An abnormal slow alpha band and polydisperse low density lipoprotein (LDL) bands were detected by agarose gel and polyacrylamide gel electrophoresis. The slow alpha band was considered as an apo E-rich HDL. A peak of large HDL particle and a peak of abnormal high-molecular-LDL particle were observed in the patient's serum by gel permeation high performance liquid chromatography. Cholesteryl ester transfer activity (CETA) of the patient's serum was completely deficient (0.0%/10 microliters/18 hr). From these results, it is strongly suggested that patient's hyper-HDL-cholesterolemia caused by a complete deficiency of CETA. PMID- 1434040 TI - The measurement of fibronectin concentrations in human aqueous humor. AB - The concentrations of fibronectin in aqueous humor, measured by ELISA which was developed to detect fibronectin, ranged from 5 ng/ml to 100 ng/ml. Aqueous humor was aspirated from human eyes with cataracts and glaucomas using a 26 gauge needle through the peripheral cornea before making the limbal incision into the anterior chamber during surgery. The results of the study show that the average concentration and standard deviation of fibronectin was 0.136 +/- 0.192 microgram/ml in cataract eyes, and 0.962 +/- 0.918 microgram/ml in glaucoma eyes respectively. There was a statistically significant difference between both groups (p = 0.000). However, no significant differences according to age and sex were noted. There was no influence due to preoperative intravenous mannitol injection on fibronectin concentration. The source of aqueous fibronectin is still not clearly known and the mechanism of the higher concentration of fibronectin in glaucoma has not been clearly disclosed, however it is thought that normally present fibronectin is accumulated in the anterior chamber because it can not pass the aqueous outflow pathway, or that fibronectin production may be increased in glaucoma. PMID- 1434041 TI - Clinical efficacy of topical homologous fibronectin in persistent corneal epithelial disorders. AB - The clinical efficacy was investigated of topical homologous fibronectin on persistent corneal epithelial defects of various etiologies. Fibronectin was purified from blood bank homologous plasma by gelatin-Sepharose 4B affinity chromatography. Twenty eight eyes of twenty five patients with persistent corneal epithelial defects and sterile corneal ulcers that failed to improve with standard therapy were treated by the instillation of homologous fibronectin eyedrops 5 times a day (500 micrograms/ml). Complete reepithelialization was achieved in all patients except two eyes due to uncontrolled glaucoma and the taking of steroids. The healing time tended to be different depending on the duration of persistent corneal epithelial defects and the severity of underlying diseases. The mean +/- standard deviation duration of epithelial defect was 68.18 +/- 77.80 days. Average healing time was 42.07 +/- 17.47 days. Ocular symptoms were relieved significantly and no side effects were observed. Over an average follow-up period of about 8 months, two cases of recurrences were noted. These results show that homologous fibronectin was also effective in patients with persistent corneal epithelial defects and corneal ulcers. PMID- 1434042 TI - Ocular dimensions with aging in normal eyes. AB - To quantify the dynamic changes taking place in the anterior segment, we measured the anterior chamber depth (ACD), lens thickness (LT) and their difference between sexes and age groups in normal eyes using contact ultrasonography and anterior chamber photography. There were 141 women (241 eyes) and 76 men (130 eyes) between the ages of 10 and 70 years. In normal eyes, the lens thickness was increased and the anterior chamber depth was decreased with aging in both sexes. The anterior chamber depth showed an accelerated decrease between the 4th and 5th decades in females and the ratio of anterior chamber depth to axial length was smaller in females than in males after the 5th decade. The results suggested that the prevalence of angle closure glaucoma will be increased in females after middle age. PMID- 1434043 TI - Optic disc of the myopic eye: relationship between refractive errors and morphometric characteristics. AB - Because the optic disc in myopic eyes is different from a normal optic disc, there are many difficulties in examining the optic discs of myopic eyes. To study optic disc change due to myopia, we performed a morphometrical study of stereophotographs of 61 men, 109 eyes, who had no glaucoma history. The range of refractive error was from +0.75 diopter to -12.75 diopter, and all subjects had intraocular pressure below or equal to 21 mmHg. According to the increase in the myopic degree, the temporal slope of the disc cup was significantly decreased, but the ratio of the vertical disc diameter (VDD) to the horizontal disc diameter and the ratio of the width of peripapillary atrophy (PPA) to the VDD were significantly increased. The above results suggests that in high myopia the optic disc was tilted and the rim-cup border was indistinct and there are some problems in the estimation of the morphometric parameters. Also in evaluation of the PPA of myopic glaucoma patients, there may be some difficulty in deciding whether it is due to myopic change or glaucomatous damage. PMID- 1434044 TI - The components of the proliferative membranes in retinopathy of prematurity: an electron microscopic study. AB - Electron microscopic examination of proliferative membranes in retinopathy of prematurity (ROP) was performed in order to evaluate the components of the membranes. The proliferative membranes were obtained from nine patients with ROP stage 5 during pars plicata lensectomy, vitrectomy, and delamination of membrane. Fibrous astrocytes, myofibroblasts, lymphocytes, macrophages, and calcification were found respectively in two cases, and fibroblast-like cells were found in one case. Varying amounts of collagen tissues were found in eight cases and vascular tissues in four cases. Most of membranes were hypocellular and composed mainly of collagen matrix. It is considered that fibrous astrocytes, myofibroblasts, fibroblasts, and vascular structures are involved in the formation of proliferative membranes of ROP, and that later these cells degenerate and disappear, and that finally only collagen matrix remains in the membranes. PMID- 1434046 TI - Unilateral congenital ocular motor apraxia: a case report. AB - Congenital ocular motor apraxia (COA), first described by Cogan in 1953, is a rare disorder which shows characteristic defects of the horizontal voluntary saccades, and compensatory head thrust. Until now, most cases have showed a presumably congenital origin, bilaterality, and a tendency to various stages of recovery with aging. But the cause and mechanism of COA are not completely known. Occasionally, it combines with other neurologic abnormalities and metabolic diseases such as Gaucher's disease exhibit similar clinical characteristics to COA. We recently experienced a case of a 3-year-old girl who showed the clinical features of unilateral congenital ocular motor apraxia. PMID- 1434045 TI - Myopia in premature infants at the age of 6 months. AB - The authors performed cycloplegic refractions in 180 eyes of 99 premature infants at the age of 6 months to evaluate the incidence and the degree of myopia according to the development and disease course of retinopathy of prematurity (ROP) and to investigate the effect of cryotherapy on the refractive error. The incidences of myopia were not different between premature infants without ROP and premature infants with spontaneously and totally regressed ROP (36.3%, 25.5%), and the degrees of myopia were low in both groups (-1.76 D, -2.25 D). In premature infants with totally regressed ROP after cryotherapy, the incidence of myopia was high (75.5%) but the degree of myopia was low (-3.03 D). In premature infants with cicatricial ROP, cryotreated or not, both the incidence and the degree of myopia were high (93.9%, -5.50 D). It is suggested that cryotherapy increases the incidence of myopia but the degree of myopia induced by cryotherapy is low. PMID- 1434047 TI - Effects of aqueous humor on filtering bleb in rabbits. AB - Preoperative aqueous humor, known to inhibit the growth of fibroblasts in tissue culture assay, was used as an adjunct to filtering surgery in rabbits to determine its effect in vivo on the outcome of filtering surgery. Fifteen rabbits underwent a posterior-lip sclerectomy in both eyes. In experimental eyes 1.4 ml preoperative aqueous humor and in fellow eyes 1.4 ml balanced salt solution were injected intracamerally. Gross and histopathological differences of bleb were observed. In this animal experiment, although there was no statistical significance or late postoperative effect, the rabbit eyes refilled with preoperative aqueous humor intracamerally just after filtering surgery, had a larger bleb and less fibroconnective tissue on the bleb than the control eyes in the early postoperative period. PMID- 1434048 TI - [Recent therapeutic advances in geriatric neurology]. AB - Marked advances in the treatment of neurological disorders which affect the elderly have been established in recent years. Cerebrovascular disorders including stroke and vascular dementia are still among the most frequent diseases in the Japanese elderly. For treatment of hypertensive patients with or without a history of stroke, slight decrease of blood pressure (BP) is recommended since recent PET studies have revealed that an excessive drop of BP markedly decreases cerebral blood flow. Furthermore, 24-hour-monitoring of BP revealed that physiological fluctuation of BP consisting of high daytime BP and low nocturnal BP disappears in hypertensive patients with vascular dementia and those with non symptomatic vascular lesions on MRI. Recommendable BP levels for the hypertensive elderly must be established. The efficacy of both aspirin and ticlopidine for prevention of stroke has been established. Recent multi-centric trials have revealed that ticlopidine is more effective in preventing stroke but has more dangerous adverse effects than aspirin. Aspirin is reported to improve both the intellectual scale and cerebral blood flow in vascular dementia. In Parkinson's disease (PD), L-DOPA therapy, usually in combination with a dopa decarboxylase inhibitor, is common. Other dopaminergic drugs including bromocriptine, lisuride and pergolide are used clinically or are being studied. Recently selective monoamine oxidase (MAO) B inhibitors have been used in order to slow clinical progression of the disease, in addition to an attempt to increase the potential of dopamine through inhibition of MAO. Neural transplants to the striatum of PD were first applied using autografts of the adrenal medulla in 1985, but resulted in transient or only slight improvements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434049 TI - [Altered bone metabolism in db/db mice]. AB - Bone and calcium metabolism was investigated in genetically obese, diabetic db/db mice and compared with that in a new hypoglycemic agent (AS-6) treated db/db mice and in their lean litter mates as controls. The 5-week-old db/db mice (serum Ca 9.88 +/- 0.22 mg/dl, glucose 258.6 +/- 13.3 mg/dl) were randomly divided into two groups. One group, together with their lean litter mates, was fed a commercial diet (CE-2). The other db/db group was fed CE-2 diet containing 0.1% of AS-6. Both groups were fed for 20 weeks. The serum glucose and calcium levels in db/db control groups (serum Ca 12.3 +/- 0.1 mg/dl, glucose 650.2 +/- 23.9 mg/dl) were higher than those in lean control groups (Ca 9.8 +/- 0.2 mg/dl, glucose 180.7 +/- 10.1 mg/dl). The wet, dry and ashed weights of the femur in db/db control were significantly lower and the length of femur in db/db control was significantly shorter than those of lean controls. These data suggest that retarded bone growth in db/db mice is related to progression of diabetes. Although, there was no change in Ca/P, Ca/ash and total perimeter in femurs, the cortical area in the femurs of db/db control mice (0.65 +/- 0.02 mm2) was significantly smaller than that of the femurs of lean control mice (0.74 +/- 0.02 mm2). The cortical bone thinning observed in the db/db control could have been caused by increased bone resorption. Treatment with AS-6 for 20 weeks resulted in a 48.6% decrease of serum glucose and 5.2% decrease of calcium as compared with db/db controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434050 TI - [Silent lacunes in the elderly Parkinson's disease correlated with ambulatory blood pressure]. AB - Lacunes on brain MRI, causal blood pressure, 24-hour ambulatory blood pressure and common carotid blood flow measured by the doppler method were studied in 31 elderly patients with Parkinson's disease (mean age 67.5 +/- 7.3 years). Nineteen patients with Parkinson's disease (61%) had at least one lacune. Patients with lacunes (P(+)) were significantly higher in age than patients without lacune (P( )). The difference of casual blood pressure between patients in the two groups was not significant. On the other hand, the average of ambulatory blood pressure measurements during a 24-hour period was significantly higher in the P(+) group than in the P(-) group. The average of carotid blood flow was also significantly lower in the P(+) group than in the P(-) group, however, after adjustment for age, the difference between them became insignificant. In conclusion, the incidence of silent lacunes on brain MRI was fairly common in elderly patients with Parkinson's disease. A high average 24-hour ambulatory blood pressure was suggested to be one of the risk factors of lacunar stroke in elderly cases of Parkinson's disease. The concept of "combine type" in Parkinsonism was supposed to be suitable as well as in senile dementia of Alzheimer type. PMID- 1434051 TI - [Analysis of nocturnal disturbed breathing in the elderly using desaturation index]. AB - This study was conducted to examine the nocturnal ventilatory parameters and gas exchange in the elderly with nocturnal disturbed breathing. In order to facilitate analysis of ventilatory parameters with minimum manpower, we developed an unattended continuous nocturnal monitoring system for ventilation and arterial oxygen saturation. Using this system, nocturnal ventilatory parameters and gas exchange were investigated in our geriatric ward. We investigated 30 elderly subjects aged between 65 and 94 (mean age 77.8 +/- 6.5 years, male; female = 15:15). The subjects were free of severe cardiovascular and cerebrovascular disorders, and underwent 10 hours of continuous monitoring of ventilation and arterial oxygen saturation (SaO2). Number of significant desaturation (SDS; desaturation greater than 4% in SaO2 from the baseline value) and desaturation index (DI; sigma SDS(%) x duration (hour)) were calculated using the same system. The number of apnea episodes significantly correlated with DI and the number of SDS. DI also significantly correlated with lowest SaO2, while the number of SDS and the number of apneas were not found to be correlated with lowest SaO2. The number of SDS and the number of apnea episodes did not correlated with lowest SaO2. From the view point of gas exchange during the night, newly introduced DI is more comprehensive parameter when compared with the number of apneas or SDS. Subjects with a DI of over 0.5 were assigned to the group A (n = 8, mean age = 77.8) and the remaining subjects were assigned to group B (n = 22, mean age = 77.8). We compared the group A with the group B regarding nocturnal ventilatory parameters and SaO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434052 TI - [Serum lipids, lipoproteins and apolipoproteins in patients with senile dementia]. AB - Serum lipid, lipoprotein, apolipoprotein, and sterol profiles were studied in 22 patients with senile dementia of the Alzheimer type (SDAT) and 29 patients with vascular dementia (VD). Levels of high density lipoprotein-cholesterol (HDL-C) were lower in both patients groups of SDAT and VD than in control group. Apolipoprotein AI and AII are two major proteins in HDL. In this study, apolipoprotein AI levels were normal, but apolipoprotein AII levels were lower in the patient groups, especially in the VD group, than in the control group. Lipoprotein(a) levels were higher in both patient groups, especially in the VD group. There were no differences of cholesterol, cholesterol precursors (desmosterol and lathosterol), and plant sterols (campesterol and beta sitosterol) among the three groups. Murine apolipoprotein AII is a serum precursor of murine senile amyloid protein, and the apolipoprotein AII variant with proline-->glutamine substitution at position 5 in the serum of accelerated senescence-prone mice is identical to the murine senile amyloid fibril protein from amyloid-deposited tissues of these mice. In human SDAT and VD, the reason for the low level of apolipoprotein AII remains unclear. PMID- 1434053 TI - [Clinical characteristics of postinfarction left ventricular aneurysm with extensive calcification]. AB - The authors experienced 4 cases of calcified postinfarction aneurysm of the left ventricle. They were all male, aged 55 to 71 (mean 64). Risk factor for coronary artery disease was only smoking in 2 patients, but there was none in the others. They had had acute anteroseptal or extensive anterior infarction at age 41-57 years (mean 49.3), and associated major cardiac events 10-22 years (mean 14.5) after acute myocardial infarction. Ventricular tachycardia, congestive heart failure and systemic thromboembolism were seen in 4, 2 and 1 patients respectively. However, none developed angina pectoris. In the 2 patients in whom signal-averaged electrocardiogram was performed, late potential was detected, so it was suspected that ventricular tachycardia could be due to reentry. Left ventricular end-diastolic pressure was elevated in all patients except one and ranged from 11 to 22 mmHg. Left ventricle was dilated in all cases and the end diastolic volume index ranged from 143 to 503 ml/m2. The left ventricular ejection fraction ranged from 11 to 24%. However, in 2 of the 4 patients, the cardiac index was within normal limits, and evidence of congestive heart failure was absent. In 2 other patients with associated congestive heart failure, cardiac indices were 2.32, 1.56 l/min/m2 respectively. Coronary arteriogram showed a total occlusion in the left anterior descending (LAD) artery in all cases, and only the LAD artery was affected in 2 patients. In the remaining 2 patients, the right coronary arteries also were significantly stenotic or totally occluded, i.e., they had 2-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434054 TI - [Successful treatment with vincristine for an elderly patient with idiopathic thrombocytopenic purpura]. AB - A 77-year-old female was referred to our hospital in March 1991 because of a severe bleeding tendency. Her blood count on admission was as follows: Hb 7.5 g/dl, WBC 4.6 x 10(9)/l with normal differentiation and platelet 2 x 10(9)/l. One month prior to admission, her blood count was normal. Initially, acute idiopathic thrombocytopenic purpura (ITP) was suspected, because of the acute onset of the bleeding tendency and thrombocytopenia. High dose intravenous immunoglobulin (400 mg/kg/day for 5 days) and bolus methylprednisolone (1 g/day for 3 days then tapered) were administered, starting March 13. Her platelet count had increased immediately on March 20 to 40 x 10(9)/l. However, platelet count decreased to 4 x 10(9)/l in the following two weeks. Her clinical course differed from that of typical acute ITP. Because the treatment with prednisolone was not effective, it was changed to intravenous infusion of vincristine (VCR) at a weekly dose of 1 mg for 6 weeks. The treatment was extremely effective, and her platelet count reached over 200 x 10(9)/l. The treatment was discontinued. Three weeks later, her platelet count decreased to 15 x 10(9)/l, the administration of VCR was resumed, and her platelet count recovered again. Throughout her clinical course, no side effect of VCR was noticed except for mild hypesthesia of the fingertips. VCR therapy was considered to be an useful treatment in elderly patients with ITP. PMID- 1434055 TI - [Two autopsy cases of aortitis syndrome in the elderly]. AB - Two autopsy cases of aortitis syndrome (Takayasu's aortitis) in the elderly are presented. Case 1 was an 81-year-old woman in whom hypertension was observed at age 37, and difference of right and left arm blood pressure was pointed out at age 65. She was referred to the authors' hospital at age 72. Chest X-ray and computed tomography of the thorax indicated atypical coarctation and diffuse calcification of the aorta. Case 2 was a 69-year-old woman in whom hypertension was pointed out at age 49, and blood pressure in the arms was found to differ from that in the legs at age 63. Chest X-ray and computed tomography showed diffuse calcification and marked narrowing of the descending aorta. Pathological examination revealed marked calcification in the thickened adventitia of the aorta with mild atherosclerotic change. Irregular fibrotic changes of the adventitia and degeneration of elastic fibers of the media of the aorta were noted in both cases, and were consistent with Takayasu's aortitis. This disorder is common in young women and only a small number of elderly cases are reported although its incidence is increasing. Diffuse calcification of the aorta with an absence of inflammatory signs, which is frequent in older patients, were observed in both case. Systemic hypertension is the most important risk factor with coarctation of the aorta in Takayasu's aortitis. Bypass surgery is recommended in young patients, however in elderly patients, it is generally avoided, in favor of medical control of hypertension. PMID- 1434056 TI - [Three cases of Chilaiditi's syndrome--hepatodiaphragmatic interposition of the colon]. AB - Three cases of Chilaiditi's syndrome are reported. Case 1: A 56-year-old woman was admitted with dysphagia. She had been suffering from progressive systemic sclerosis for 16 years. Three years before the admission, dysphagia developed and dilatation and hypomotility of the esophagus were observed. Chest and abdominal x ray films on admission showed severe dilatation of the intestine, pneumatosis cystoides intestinalis, abdominal free air, and Chilaiditi's syndrome. Chilaiditi's syndrome and other signs disappeared after conservative treatment. She died four months later due to cor pulmonale. Case 2: An 87-year-old man was admitted with constipation and left lower abdominal pain. Physical examination showed ascites. Chest and abdominal x-ray examination showed Chilaiditi's syndrome. Cytological examination of ascites revealed adenocarcinoma cells. Diagnosis of peritonitis carcinomatosa due to cancer of pancreatic tail was made. Chilaiditi's syndrome disappeared after removal of ascites. Case 3: A 71-year-old bedridden man who had urinary incontinence developed meterorism. Repeated chest x ray examinations constantly showed Chilaiditi's syndrome. He died of pneumonia two years later. The pathogenesis of Chilaiditi's syndrome was discussed and the literature was reviewed. PMID- 1434057 TI - [A case of recurrent cerebral hemorrhage considered to be cerebral amyloid angiopathy by cerebrospinal fluid examination]. AB - A 73-year-old man was admitted with gait disturbance and dysarthria. He showed right-side cerebellar ataxia. Computed tomography of brain showed left thalamic bleeding. Nine months later, he was admitted again because of seizure and consciousness disturbance. He had a history of diabetes mellitus and gout for five years, but no hypertension. On physical examination the lungs and heart were normal. On neurological examination, he showed stupor,pupils and eye position were normal. He showed right hemiparesis and urinary incontinence. The deep tendon reflexes were (+) at the upper limbs and (2+) at the right knee and ankle. Blood pressure was 162/88 mmHg and glucose was 275 mg/dl. Other laboratory data were normal. Brain CT showed hemorrhage of the left frontal lobe. The cystatin C level in cerebrospinal fluid was 68 ng/ml. Therefore we suspected cystatin C deposit amyloid angiopathy. In this case, thalamic hemorrhage was initially thought to be amyloid angiopathy. In cases of cerebral hemorrhage in the elderly without hypertension, we must be considered amyloid angiopathy. PMID- 1434059 TI - [Neuropathological study of amyotrophic lateral sclerosis in relation to aging]. AB - It has been assumed that amyotrophic lateral sclerosis (ALS) involves precocious senility as one of its pathogenetic aspects. The authors studied 55 autopsied cases of ALS in relation to age at death, ranging from 42 to 86. The materials consisted of 8 cases in the fifth decade, 8 in the sixth, 20 in the seventh, 12 in the eighth, and 7 in the ninth. The total duration of illness ranged from 6 months to 14 years. The most distinct relationship was observed in the anterior horn lesion of the cervical enlargement which became less severe with advancing age, irrespective of the length of illness. Fifth decade cases showed marked atrophy with severe neuronal loss and fibrillary gliosis in the anterior horn, while those in the ninth decade showed slight changes which were similar to age matched controls. On the other hand, pyramidal tract degeneration did not show any correlation to age at death or to length of illness. Pyramidal tract degeneration was found in all younger age group cases, being always severe. In the older age groups, however, the degeneration varied extremely in degree from case to case. Some cases showed severe degeneration comparable with that in the younger age groups, while the others had no findings suggesting degeneration. In addition, cases on artificial respirators had a longer duration of illness, and more marked degeneration in the anterior horn, irrespective of age. Our study did not reveal that senile changes including senile plaques and neurofibrillary tangles were more marked in ALS cases. No clinicopathological correlation with dementia was recognized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434058 TI - [Prognostic analysis for postoperative complications of abdominal surgery in the elderly]. AB - In order to evaluate the prognostic importance of the conditions before abdominal surgery for patients over 60 years of age. Multivariate analyses of postoperative complications were performed in 634 patients (comprising 525 cases of elective abdominal surgery and 109 cases of emergency abdominal surgery). The Mortality rate was significantly higher (p < 0.01) in the emergency group (11.9%) and relatively low among the elective abdominal surgery group (3.8%). In the emergency group, 13 patients died, and MOF (multiple organ failure) was found to be the direct cause of death in 11 (85%). Although, the majority (75%) of emergency operations were for benign disorders, the remainder (25%) had malignant tumors. It is noteworthy that among 25% of cases, obstructions and perforations due to large bowel cancers were found to be 59% and 19%, respectively. In the elective surgery group, postoperative pulmonary and cardiovascular complications were found in 11.6% and 9.6%, respectively. Death due to cardiovascular problems in rare (5%), however, postoperative pneumonia was the cause of death in 70% of all of postoperative death. Risk factors affecting postoperative pulmonary complications were malnutrition, advanced age, male sex, malignant disease, dementia, cerebrovascular disorders, impaired pulmonary function tests. Surprisingly, the risk factors were identical, except for impaired pulmonary function, for postoperative MRSA pneumonia. In our study, postoperative pulmonary death was not associated with impaired pulmonary function, and it appears to be rather affected by the presence of cerebrovascular disorders and malnutritional state. A poor nutritional states (< 40 according to Onodera's nutritional index) was present in over 50% of patients with cerbrovascular disorders and low ADL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434060 TI - [Immunological functions and clinical course of elderly patients with cerebrovascular diseases]. AB - In the elderly, cerebrovascular diseases (CVD) are often complicated by severe infections such as pneumonia. This study aimed to examine the possible relationship at various timepoints of observation between immunological functions and the clinical course and to correlate the changes of immunological functions with CVD lesion side. The study was based on 25 right-handed patients (14 male and 11 female, mean age; male 69.0 years and female 74.9 years) with acute, focal neurological deficits of CVD (5 cerebral bleeding, 20 cerebral infarction; 11 right cerebral lesioned subjects, 14 left cerebral lesioned subjects). All patients were evaluated in terms of lymphocyte counts, T, B cell counts, T cell subsets, lymphocyte transformation and natural killer activity in peripheral blood as indices of immunological functions at various timepoints during the clinical course. Some of these immunological functions decreased within two months (acute stage) after onset of CVD, and some cases with decreased immunological functions developed complications of severe infection such as pneumonia. Patients who had both decreased immunological function and severe infection were 1 out of cases with 7 right cerebral lesions and 6 out of with 9 left cerebral lesions. This study suggests that the decreased immunological function in CVD subjects may be correlated with the site of the CVD lesion. In all left cerebral lesioned subjects, a reduction of immunological functions and a susceptibility to severe infection were not observed in the acute stage of CVD, however, some left cerebral lesion cases may be more closely related than in right cerebral lesion cases. The mechanism remains to be clarified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434061 TI - [Postprandial hypotension in the elderly with and without hypertension]. AB - To clarify the mechanism of postprandial hypotension in the elderly, blood pressure and humoral factors were measured before and after meal, water, and glucose ingestion in 20 healthy elderly. The elderly patients were divided into 10 normotensive and 10 hypertensive cases. A reduction in systolic BP after meals in the hypertensive group was significantly larger than that in the normotensive group (-12.0 +/- 4.1 vs. 4.0 +/- 3.2 mmHg, p < 0.05). Systolic BP in hypertensive group significantly decreased at 30, 45 and 60 minutes after meals compared to the value before meals. However, no significant reduction in systolic BP was observed in the normotensive group. A change in systolic BP after meal significantly correlated with that after glucose, but not with that after water ingestion, suggesting that glucose intake mainly contributes to the postprandial hypotension in the elderly. An increase in plasma renin activity and plasma catecholamine were observed after meals in the normotensive group, but not in the hypertensive group. An increase in systolic BP significantly correlated with an increase in PRA. It was suggested that an impairment of the sympathetic nervous system in the elderly with hypertension was involved in the mechanism of postprandial hypotension. PMID- 1434062 TI - [Long-term nasogastric feeding and complications of acute gastric ulcer in two elderly patients]. AB - Some elderly patients with chronic illness such as stroke, or Parkinsonism cannot take food orally because of dysphagia. In such cases, tube feeding can be used as a supplement to oral intake when malnutrition is present. This route allows for easier nursing care and decreases the frequency of aspiration pneumonia. Complications of tube feeding include nutrient deficiency states, pulmonary aspiration, gastrointestinal and metabolic disorders. We report two cases with complications of acute gastric ulcer which was thought to be induced with long term tube feeding. Case 1 was a 61-year-old male patient with Parkinson's disease for ten years. L-DOPA had been administered with good control of his condition. However, his ability to swallow has deteriorated gradually. As he often suffered from aspiration pneumonia, nasogastric tube feeding was performed. After three years of tube feeding, he suddenly vomited much bloody material. He died from massive bleeding with acute gastric dilatation. Autopsy showed giant acute gastric ulcer covered with coagulated blood. UL3, 50 mm in maximum diameter, was observed in the middle portion of the greater curvature, where the top of tube probably came in contact with the gastric wall. Case 2 was an 83-year-old female patient with stroke and chronic heart failure. She had been hospitalized for about one year because of the intermittent deterioration of her cardiac condition. Furthermore, her inability to swallow increased during her hospitalization. She also suffered from aspiration pneumonia. Nasogastric tube feeding was performed to prevent aspiration pneumonia and malnutrition. She died of acute heart failure after twelve months. Autopsy revealed heart dilatation, old myocardial infarction and stroke. In addition, two acute gastric ulcers (UL3.10 and 30 mm in diameter) were recognized; one was in the upper portion of the greater curvature, the other in the lower portion of the greater curvature. The location of these gastric ulcers was unusual. Moreover, they coincided with location of top of the nasogastric tube. From these two cases, we conclude that in long-term tube feeding the tip of the tube often comes in contact with the gastric wall, and gastric ulcer could be produced by repeated mechanical stimulus of the wall. Reports of acute gastric ulcer induced by tube feeding have not been published previously. Therefore, we should pay much attention to this complication in the care of the elderly people with long-term tube feeding. PMID- 1434063 TI - [An 88-year-old female case of hyperalphalipoproteinemia associated with deficiency of cholesteryl-ester transfer activity]. AB - An 88-year-old female was admitted to our hospital for examination of hyperalphalipoproteinemia. The high level of her serum high-density lipoprotein cholesterol (HDL-C, 148 mg/dl) was due to cholesterol amount of HDL2-C but not HDL3-C, and serum cholesteryl ester transfer activity (CETA) was at a non detectable level. Despite her age, apparent atherosclerotic changes were not observed. She may be the oldest case of hyperalphalipoproteinemia, possibly due to deficiency of serum CETA. PMID- 1434064 TI - [A case of amnesic stroke caused by left hippocampal infarction]. AB - A 78-year-old woman was admitted to our hospital because of acute onset amnesia in March 1991. Neurological examination revealed right homonymous hemianopsia and clumsiness of the right hand. Magnetic resonance imaging (MRI) demonstrated abnormal intensity areas in the left hippocampus, parahippocampal gyrus, fimbria of the hippocampus and the occipital lobe. Immediate memory and long-term memory were relatively well-preserved, but short-term memory was severely disturbed. Her memory disturbance persisted for more than 9 months and she eventually developed an "amnesic stroke". According to the MRI findings, the "amnesic stroke" was produced by infarction of the left hippocampus, parahippocampal gyrus and fimbria of the hippocampus. We emphasized that in this case an "amnesic stroke" was caused by infarction of the left hippocampal lesions. PMID- 1434065 TI - [Non-Hodgkin's lymphoma in an elderly patient complicated by cyclophosphamide induced allergic hepatic dysfunction]. AB - A 77-year-old male presented at our Department of Urology in August 1990 with a gradually enlarging swelling in the right scrotum. On August 21, right high orchietomy was performed. This was diagnosed histologically as non-Hodgkin's lymphoma (diffuse large cell type), and the patient was transferred to our department on September 11 for further examination and treatment. As enlargement of the lymph nodes around the abdominal aorta was evident, it was diagnosed as stage IIA according to the Ann Arbor Classification. Beginning on September 21, three courses of COP-BLAM therapy (CPM, VCR, PDN, BLM, ADR, PCZ) were administered (the third course started on November 8) to achieve complete remission. Hepatic dysfunction appeared, however, from November 16, and by November 19, GOT and GPT increased to 6700 and 2120, respectively, with aggravation of jaundice. PDN therapy was instituted, and GOT and GPT improved gradually, but jaundice did not improve. On December 22, laparoscopy was performed, and liver biopsy produced histologic findings of drug-induced hepatitis. Further, lymphoblastic response was positive for CPM. Hepatic failure occurred on December 29, and plasma exchange was performed, but it failed to improve the condition, and the patient died on January 15. We described a case of non-Hodgkin's lymphoma complicated by hepatic dysfunction, probably induced by CPM, in an elderly patient who died to hepatic failure. PMID- 1434066 TI - [A case of choreoathetoid movements induced by anticholinergic drugs, trihexyphenidyl HCl and dosulepin HCl]. AB - We report a 72-year-old woman who showed marked orolingual dyskinesia and choreoathetoid movements of the neck, with rolling and nodding of the head. She had been treated for postural tremor and other complaints with multiple drugs, including trihexyphenidyl HCl (THP) 6 mg/day for about two years. Moreover, two months before admission to our hospital, a doctor added tricyclic antidepressant, dosulepin HCl (DL) because of her state of anxiety. Two weeks following DL administration, the persistent dyskinesia described above appeared. Suspecting the dyskinesia to be induced by anticholinergics, we withdrew THP, which decreased the intensity of the dyskinesia. Then, when DL was ceased the dyskinesia almost completely disappeared, slightly recurring only during calculating, when excited or writing. In order to confirm that anticholinergics were the cause of the dyskinesia, we administered THP 6 mg/day again. In a few days the same dyskinesia reappeared, disappearing following THP withdrawal. In this case the overlap of anticholinergics might have resulted in the dyskinesia, because both THP and DL have anticholinergic effects. It should be stressed that inappropriate administration of anticholinergics could cause severe dyskinesia in the elderly. PMID- 1434067 TI - A significant age shift of the human parvovirus B19 antibody prevalence among young adults in Japan observed in a decade. AB - A seroepidemiological study on human parvovirus (B19) in Japan was undertaken with serum samples randomly collected from healthy Japanese populations (416 in 1973, 675 in 1984 and 508 in 1987/88). All samples were tested for anti-B19 IgG antibody by the indirect antigen-capture ELISA. The antibody prevalence for ages 0-9 years old in 1984 was significantly higher (16%) than that in 1973 (2%), whereas those for ages 20-29 years and 30-39 years were significantly lower in 1984 (20% and 56%) than in 1973 (67% and 80%) (p < 0.005). After the erythema infectiosum (EI) outbreak in 1986/87, the antibody prevalences for ages 5-9, 10 14 and 15-19 years were 40-85% in Fukuoka, 0-10% in Gunma, and 21-41% in Chiba reflecting each EI incidence in these three prefectures, whereas those for ages 20-29 years remained low (< 20%). These data indicate that B19 virus was transmitted mainly among children and no significant incidence of B19 virus infection in adults has occurred since 1973, resulting in a notable shifting of B19 susceptibility toward older ages including child-bearing females. PMID- 1434068 TI - Assessment of the molluscicidal activities of Tribromosalan, Cartap and Chlorothalonil against Oncomelania hupensis. AB - Molluscicidal activities of Tribromosalan, Cartap and Chlorothalonil were evaluated in the laboratory and the field against Oncomelania hupensis, the intermediate host of Schistosoma japonicum in China. The three chemicals were very effective against O. hupensis in the laboratory. The molluscicidal activities found in the field trials suggest that Tribromosalan and Cartap may be used as practical molluscicides. Dosage of 10 g/m2 of Tribromosalan in spring only and 20 g/m2 of Cartap in both spring and autumn would be recommendable as practical mollusciciding doses for the control of O. hupensis. PMID- 1434069 TI - Isolation of spotted fever group rickettsia from Apodemus speciosus in an endemic area in Japan. AB - A spotted fever group rickettsia was isolated from Apodemus mice captured near the site where a person had been infected in Miyazaki Prefecture. Antigenic characteristics of the isolate designated as strain TO-1 were compared with those of Rickettsia japonica (strain YH) and Rickettsia montana (ATCC VR611) by the indirect fluorescent antibody test with 14 serum specimens obtained from Apodemus speciosus, immune rat antisera against the strains TO-1 and YH, and three patients' sera. The titers of these sera measured with strain TO-1 were identical to those with strain YH, suggesting the antigenic similarity between these two organisms. It was also suggested that Apodemus speciosus is likely to be an important vertebrate host for a spotted fever group rickettsia in Japan. PMID- 1434070 TI - [Radionuclide study of left ventricular function and regional myocardial perfusion in patients with a DDD pacemaker]. AB - In order to determine the influence of right ventricular artificial pacing on left ventricular function, particularly on diastolic specificity and regional myocardial perfusion, 99mTc multigated blood pool study and 201Tl myocardial SPECT at rest were performed on 12 patients with a DDD pacemaker implanted due to atrio-ventricular block at various degrees and on 7 normal adults without pacemaker as controls. Studies were performed on the pacing group during both ventricular pacing (VP) and atrio-ventricular sequential pacing (AVSP) at a rate of 80 beats/min. Although global left ventricular ejection fraction (LVEF) showed no significant differences between the control group (63.7 +/- 9.1%) and the pacing group, or between during AVSP (57.8 +/- 9.6%) and during VP (55.8 +/- 10.0%), global early diastolic peak filling rate (EDPFR) in the pacing group were significantly lower during AVSP (0.90 +/- 0.52 counts/second/end-diastolic counts) than during VP (1.55 +/- 0.52) (p less than 0.01), which were both found to be lower than those seen in control group (2.37 +/- 0.48 (p less than 0.01). Functional images disclosed regional prolongation of left ventricular ejection time (ET) in septal and apical areas of the left ventricle adjacent to the pacing site in 7 of the 12 patients (58.3%) during AVSP and in 3 of them (25%) during VP, and also revealed regional decrease in EDPFR in the similar areas in all of the patients during both modes, being more remarkable during AVSP than during VP. On 201Tl myocardial SPECT at rest, regional perfusion impairment was observed in septum, apex and the infero-posterior wall on the septal side adjacent to the pacing site in 8 of 10 patients (80%) during AVSP and in 6 of 9 patients (66.7%) during VP. These results suggest that a change in electrical conduction by right ventricular pacing may disturb regional myocardial relaxation, probably resulting in a regional impairment of myocardial perfusion. PMID- 1434071 TI - [The utility of quantitative 99mTc-GSA liver scintigraphy in the evaluation of hepatic functional reserve: comparison with 99mTc-PMT and 99mTc-Sn colloid]. AB - Using data from 17 patients with liver cirrhosis and 3 patients with fatty liver, we have compared the utility of 3 hepatic imaging agents in the evaluation of hepatic functional reserve. Evaluated here were 99mTc-galactosyl human serum albumin (GSA) which is a new ligand for hepatic binding protein, 99mTc-N pyridoxyl-5-methyl tryptophan (PMT) of a hepatobiliary agent, and 99mTc-Sn colloid. In each patient, we performed these 3 imaging studies within a week and also examined hepatic function tests (indocyanine green test, hepaplastin test, choline-esterase, etc). In each imaging study, serial images and dynamic data were obtained after the injection of 99mTc-GSA (185 MBq/3 mg), 99mTc-PMT (185 MBq), or 99mTc-Sn colloid (185 MBq). Using the obtained dynamic data, we analyzed the liver kinetics of the 3 agents based on 1 compartment model with 3 parameters (hepatic clearance, hepatic excretion rate, non-specific volume of distribution). From fitting the liver and heart data to this model, three unknown parameters were determined. Patlak plot was also applied in order to estimate liver uptake rate. Both curve fitting and Patlak plot could determine appropriate parameters in every study. In 99mTc-GSA, a nonlinear 3 compartment model was also applied in order to estimate hepatic blood flow, liver receptor density, and affinity of receptor-GSA binding separately. Using the obtained parameters, we analyzed the correlations between the parameters and the results of hepatic function tests. In all of the parameters, those obtained from 99mTc-GSA imaging showed the most significant statistical correlation with the results of hepatic function tests. From the present results, 99mTc-GSA imaging was concluded to be the best for evaluation of hepatic functional reserve. PMID- 1434073 TI - [Estimation of perioperative myocardial infarction in patients under aorto coronary bypass grafts with plasma level of myosin light chain I and 201Tl SPECT]. AB - After aorto-coronary bypass grafts surgery plasma level of myosin light chain I, determined with monoclonal antibodies to myosin light chain I (LC-I), were studied in 12 patients (pts) without electrocardiographical perioperative myocardial infarction. Rest 201Tl myocardial images were collected before and after surgery. LC-I increased and reached peak levels (15 +/- 7 ng/ml) at 91 +/- 29 minutes after the aortic declamp. From peak levels LC-I rapidly decreased with fast half-time disappearance (1.4 +/- 0.9 hours). In 5 pts of 12 pts LC-I recovered to normal range and MB reached maximum levels (34 +/- 23 IU/L) at 18 +/ 9 hours after declamp. In 4 pts 201Tl images showed improvement and in one 201Tl images showed no changes. In 7 pts of 12 pts LC-I decreased to minimum levels (2.7 +/- 0.6 ng/ml) at 12 +/- 6 hours and then gradually increased to peak levels (5.6 +/- 0.9 ng/ml) on day 3 +/- 0.9. MB reached maximum level (61 +/- 20 IU/L) at 3.2 +/- 1 hours. In 201Tl images 3 pts showed suspected new lesion, 2 pts showed no changes and 2 pts showed improvement. No correlation was noted between peak LC-I level and duration of aortic declamp. No significant relation was suspected between early LC-I peak and irreversible myocardial cell injury. From close relationship between aortic declamp and appearance of LC-I peak, it was concluded that LC-I, accumulated during aortic clamp, was washed out by aortic declamp. Relation was suspected between early LC-I peak and myocardial injury during myocardial protection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434072 TI - [Pulmonary clearance of 99mTc-DTPA aerosol in patients with progressive systemic scleroderma]. AB - Alveolar epithelial permeability was assessed in 32 patients with progressive systemic scleroderma (PSS), using 99mTc-DTPA aerosol. Immediately after the inhalation of 99mTc-DTPA aerosol for 3 to 6 minutes under normal tidal breathing, lung was imaged sequentially for 30 minutes from the posterior by a gamma camera and exponential fitting was processed on the time activity curve. T1/2 (min) was used as a parameter for the evaluation of permeability of alveolar epithelium. Patients with collagen disease showed shorter T1/2 (T1/2 = 43.7 +/- 23.8 min) than the normal volunteers (T1/2 = 76.8 +/- 8.7 min). No significant difference was observed between patients with or without interstitial changes on the chest CT. Significant correlation was not observed between T1/2 and %VC or %DLco. In 8 cases, studies were repeated in the interval of 3 to 19 months. Improvement of T1/2 was seen in 4 cases, independent of CT findings. These results suggest that 99mTc-DTPA aerosol clearance study provides information independent from other lung examinations, and may be useful for the assessment of lung interstitial changes in patients with PSS. PMID- 1434074 TI - [Diffusely increased uptake in the skull in normal bone scans]. AB - Diffusely increased skull uptake (a hot skull) is often seen in patients with bone metastases and metabolic diseases. This finding is also, however, noticed in normal bone scans of aged women. To determine whether the hot skull could be considered a normal variant in elderly women and is associated to menopause, we studied 282 normal bone scans (166 women and 116 men without metabolic and hormonal disease; age range 11 to 84 yr). We divided the patients into eight age groups--ages 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 yrs. Measurements of skull uptake were obtained from anterior total body views using contrast-to-noise ratio (CNR). CNR for the skull was calculated using the following equation: (counts skull - counts femur)/square root of counts skull+counts femur, where the denominator signifies a measure of the noise and the numerator represents the contrast between the skull and the midfemur. Counts skull and femur are the number of average counts per one pixel recorded over the skull and midfemur, respectively. The sex dependent difference in skull uptake began to develop in the age group 30-39 yrs (p less than 0.05). The skull showed greater activity in women than in men for age groups from 30-39 to 80-89 yrs. In the age groups 50-59 and 60-69, the difference was particularly large (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434075 TI - [Assessment of myocardial viability with 201Tl myocardial SPECT 24 hours after injection]. AB - Recently many investigators reported that conventional stress-redistribution myocardial scintigraphy with 201Tl underestimated the presence of ischemic but viable myocardium. We studied the usefulness of 24 hour 201Tl myocardial single photon emission computed tomography (SPECT) to assess myocardial viability and investigated the factors affect to the quality of 24 hour SPECT images. Study patients were consisted with 70 patients with old myocardial infarction (OMI), 72 patients with angina pectoris without OMI (AP) and 43 patients with angiographically proven normal coronary arteries. To obtain SPECT images, 10 minute and 4 hour imagings were sampled 30 seconds per projection. Twenty-four hour imaging was sampled 60 seconds per projection. Twenty-four hour images were visually interpreted as good, moderate and poor quality. Then study patients were divided into 2 groups, group A with good 24 hour images and group B with moderate or poor 24 hour images. One hundred and fifty-eight patients (85.4%) of study patients had 24 hour SPECT images on a good quality. Only 4 patients (2.2%) had poor quality SPECT. All of these 4 patients had broad myocardial infarction. In patients with OMI 61 patients (87.1%), in AP 63 patients (87.5%) and in normal 35 patients (81.4%) had a good 24 hour SPECT. Total sampling counts and myocardial ROI counts were significantly higher in group A than in group B. Body weight was significantly higher and there were more male patients in group B than in group A. Late redistribution was seen in 20 patients (28.5%) with OMI and in 11 patients (15.3%) with AP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434076 TI - [Evaluation of coronary hemodynamics and exercise 201Tl-myocardial scintigraphy in patients with vasospastic angina]. AB - To clarify the coronary hemodynamics and myocardial perfusion in patients with vasospastic angina, we performed exercise-201Tl-myocardial scintigraphy (planar and SPECT) in 72 patients and left coronary digital subtraction angiography (DSA) in 37 patients without significant organic coronary artery stenosis. Coronary artery spasm was documented by coronary angiography in all patients. Fifty-four patients (75%) developed exercise-induced 201Tl-myocardial perfusion defect on SPECT. 201Tl pulmonary uptake (L/H) was significantly increased in patients with vasospastic angina. Especially, L/H was higher in patients with multiple small perfusion defect on 201Tl-SPECT, so that exercise-induced left ventricular dysfunction existed in patients with vasospastic angina and especially in cases with multiple small perfusion defect on 201Tl-SPECT. The left coronary circulation time (CCT) was prolonged in patients with vasospastic angina. The mechanism of prolonged CCT is still unknown, but we suspected that prolonged CCT was induced by increased peripheral coronary vascular resistance in patients with vasospastic angina. It was concluded that the peripheral coronary circulation was disturbed in patients with vasospastic angina, but its abnormal coronary circulation had no relation to location of spasm-induced vessels. We concluded that impaired coronary microcirculation was taken a part of pathophysiology in vasospastic angina. PMID- 1434077 TI - [Discrepancy between 123I-IMP SPECT and X-ray CT in chronic cerebrovascular disease]. AB - The discrepancy between the low accumulation area (LAA) seen on 123I-IMP SPECT and the low density area (LDA) on X-ray CT was evaluated in 76 cases with chronic cerebrovascular disease. In 19 patients, LAA was larger than LDA beyond the vascular territory. Brain angiogram showed either obstruction or stenosis of the major arteries in as many as 59 percentages of this discrepancy group. In many patients of this group, cortical neurological symptoms were observed. In 37 patients in which the size of LAA was equal to that of LDA, abnormality of the major arteries was observed in only 7 percentages. These results indicated that the discrepancy mainly reflected the infarction due to irreversible ischemic change of perforate artery with the cortical low perfusion caused by the major artery disease. In some patients, the discrepancy was believed to show the remote effect caused by neurological pathway disturbance. PMID- 1434078 TI - [67Ga scintigram and MRI in malignant bone tumors and malignant soft tissue tumors]. AB - We have analyzed the characteristics of 67Ga scintigram and MRI in 11 malignant bone tumors and 11 malignant soft tissue tumors. Osteosarcoma showed a high accumulation in 67Ga scintigram and low signal intensity in T1 weighted image. T2 weighted image were not characteristic. Chondrosarcoma showed medium 67Ga accumulation and low signal in T1 weighted image and high signal in T2 weighted image. Ewing sarcoma showed low accumulation in 67Ga scan and medium intensity in MRI. Malignant soft tissue tumors showed rather low 67Ga accumulation compared with malignant bone tumors. Malignant fibrous histiocytoma showed medium accumulation of 67Ga, low signal in T1 weighted image and high signal in T2 weighted image. Liposarcoma showed low 67Ga accumulation and medium signal in T1 weighted image and high signal in T2 weighted image. To summarize these characteristics, three dimensional display is demonstrated. PMID- 1434079 TI - [Analysis of stereoisomers involved products of synthesized 18F-2-deoxy-2-fluoro D-glucose by 1H-NMR spectroscopy]. AB - 18F-2-fluoro-2-deoxy-D-mannose (FDM) is eventually involved in side products of 18F-2-fluoro-D-glucose (FDG) synthesized by the acetylhypofluorite method. We attempted the measurement of existence ratio of FDM and FDG, FDM alpha and FDM beta, FDG alpha and FDG beta by 400 MHz 1H-NMR spectroscopy. The ratio of FDM to FDG were 4.0%. The amounts of FDG beta were much larger than those of FDG alpha. The difference between the amounts of FDM alpha and FDM beta were not significant. 1H-NMR spectroscopy could be utilized in quantitative analysis of products and byproducts in cyclotron chemicals. The FDM in FDG synthesized in our cyclotron system was not considered to affect a lot of influence in PET study. PMID- 1434080 TI - [81mKr scintigraphic evaluation of hemodynamics in gynecologic malignancies under condition of angiotensin II-induced hypertension]. AB - Transcatheter arterial infusion chemotherapy is one of the most useful therapeutic procedures for gynecologic malignancies. Recently, several reports have been published about Angiotensin II-induced hypertension chemotherapy and the efficacy of the method, but there have been no reports to evaluate an application for gynecologic malignancies. We evaluate the usefulness of the method for gynecologic malignancies demonstrating the changes of hemodynamics of the tumor using 81mKr scintigraphy. Thirteen patients with pathologically confirmed gynecologic malignancies were evaluated by angiography and continuous infusion of 81mKr via the catheter with and without Angiotensin II. At first, continuous infusion of 81mKr was performed under the superselective catheterization of the uterine artery. The radioactivities in the ROI were counted. Then, withdrew the catheter from the uterine artery to the internal iliac artery, and again continuously infused 81mKr and counted the radioactivities in the same ROI. Finally, keeping the catheter in the internal iliac artery, Angiotensin II and 81mKr were infused simultaneously. And counted the radioactivities. The radioactivities were highest when the catheter tip was placed in uterine arteries and lowest when the catheter tip was placed in internal iliac arteries. But radioactivities in the ROIs were definitely increased when Angiotensin II was used, even if the catheter tip was keeping in the internal iliac arteries. The optimal catheter position of transcatheter arterial chemotherapy for gynecologic malignancies is at proximal uterine artery. Since Angiotensin II-induced hypertension may increase blood flow of tumors, it seems to have indication for post-operative cases, highly advanced cases and cases with difficulties to perform superselective catheterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434081 TI - [The usefulness of the emergency hepatobiliary scintigraphy to rule out acute cholecystitis--43 patients report]. AB - We studied emergency hepatobiliary scintigraphy in the 43 patients to rule out acute cholecystitis. After injection of 185-222 MBq (5-6 mCi) of 99mTc-EHIDA or 99mTc-HIDA, serial static scintigraphic images were obtained up to 7 hours in maximum. Of 43 patients in this study, 20 had a normal scan and finally in all of them cholecystitis was ruled out. Of the 43 patients, 14 had an abnormal scan (nonvisualized gall bladder). In 10 of them the diagnosis of acute cholecystitis was confirmed after emergency cholecystectomy. The other 9 patients of 43 had an incomplete scan mainly due to liver dysfunction. Four of them had acute cholecystitis in the cholecystectomy. These results indicate that acute cholecystitis can be excluded by the findings of gall bladder visualization in hepatobiliary scintigram. We concluded that emergency hepatobiliary scintigraphy is very useful to rule out acute cholecystitis. PMID- 1434082 TI - [Phase I clinical study of 99mTc-ECD]. AB - A phase I clinical study of 99mTc-L,L-ethyl cysteinate dimer (99mTc-ECD) was carried out in 3 normal volunteers. There was no significant change in vital signs and laboratory parameters attributing to the radiopharmaceutical. 99mTc-ECD was rapidly taken up by the brain, reaching the maximum peak activity within 1 min after the injection and remained relatively constant over several hours. The brain uptake of 99mTc-ECD at 5 min was 5.4 +/- 0.5% which decreased to 5.0 +/- 0.3% by 65 min. 99mTc-ECD cleared rapidly from other organs. The primary excretion route was through the kidneys. Cumulative 99mTc activity in the urine at 90 min and 24 hr were 60.2 +/- 7.3% and 88.5 +/- 10.3%, respectively. The critical organ was the bladder wall with an estimated radiation dose of 0.073 mGy/MBq, which was acceptable value. Clear SPECT images were obtained at 30, 90 and 150 min postinjection. In conclusion, 99mTc-ECD is a safe and promising radiopharmaceutical for the evaluation of regional cerebral blood flow. PMID- 1434083 TI - [A case of unusually muscle localization of 99mTc-hydroxy methylene diphosphonate scintigraphy in a patient with acute rhabdomyolysis]. AB - A 85-year-old man was admitted with a history of right upper arm pain following trauma. Laboratory studies included an initial CPK level of 5,385 IU/liter. Other laboratory values were GOT, 114 IU/L; LDH, 701 IU/L; myoglobin, 1,100 ng/ml; aldolase, 13.8 IU/L. The patient was presumed to have have rhabdomyolysis. A 99mTc-hydroxy methylene diphosphonate (99mTc-HMDP) scan revealed an increased uptake in the right shoulder area. 99mTc-HMDP scan is a sensitive indicator of local skeletal muscle injury in rhabdomyolysis. PMID- 1434084 TI - [Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy]. AB - Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51 +/- 11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (greater than 2.0 mg/dl). 1) After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. 2) Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. 3) In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. 4) LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of 201Tl myocardial defect or elevated CPK. 5) The mechanism for elevated LCI in myopathy is related to a cross-reaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. PMID- 1434085 TI - [Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood--mainly in vitro]. AB - Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood was studied mainly in vitro. When 99mTc-ECD was mixed with blood taken from 12 subjects, the octanol extraction ratio of ECD (y) decreased rapidly and the octanol extraction ratio-time profile well fitted a monoexponential curve (y = Ae-kt/1000, A, k: constant, t: time after mixing). The k value and hematocrit (Ht) were significantly correlated (k = 0.376Ht-3.27, r = 0.897, p less than 0.001), therefore, it was suggested that the majority of the enzyme which dissolves ECD exists in red blood cells. When ECD was mixed with blood, there were more hydrophilic products of ECD in plasma than those generated by the enzyme in plasma. In vivo input function of 99mTc-ECD was calculated by arterial blood sampling and octanol extraction. The duration of effective input was relatively short, which was attributed to rapid decrease of octanol extraction ratio in vivo. PMID- 1434086 TI - [A new polar map to quantify reversible area by myocardial 201Tl single photon emission computed tomography and clinical application to patients before and after percutaneous transluminal coronary angioplasty]. AB - In the studies of stress 201Tl single photon emission computed tomography, we have developed a computer method to discriminate reversible from irreversible defect, then quantify each area and display the area on the polar map. Initial percent uptake (%Ui) and delayed percent uptake (%Ud) were expressed as percent of the maximum uptake area and were defined as regional myocardial 201Tl uptake in initial and delayed image, respectively. The %Ud/%Ui ratio was defined as redistribution ratio (RD-ratio). The values of %Ui obtained from each pixel of short axis slices were plotted against the values of RD-ratio on XY co-ordinates. In this graphic display, normal area, ischemic viable area and non viable area were separated by the following four lines. A; The straight line (Y = 2.0-0.012X) indicating the relationship between %Ui and RD-ratio for the group with ischemic viable myocardium. B; The parallel line to A and shifted to -1.5 SD from A. C; The vertical line at 67.0% level (ischemic upper level). D; The vertical line at 27.6% level (viable lower level). Each area was discriminated by color display and calculated relative area values were displayed on the polar map. Criteria for discriminating each area were derived from the results of ischemic pre transluminal coronary angioplasty (PTCA) lesions (n = 21) in which viability was confirmed by successful PTCA and previous results of 66 cases with single vessel disease and 16 cases of control group. This new computerized technique was applied for evaluation of another group with successful PTCA (n = 15).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434087 TI - [Phase III trial of 99mTc-rhenium colloid for lymphoscintigraphy]. AB - A multicenter study was carried out on 191 patients (196 examinations) with lymphatic system disorders to evaluate the efficacy and safety of 99mTc-rhenium Colloid, a tracer for lymphoscintigraphy (TCK-17). Local pain and swelling occurred at the site of injection in 79.6% and 5.1% of patients, respectively, and 2 patients experienced mild fever. The accuracy was calculated on the basis of the results obtained by other diagnostic methods. Lymphoscintigraphy using TCK 17 was sensitive diagnostic procedures, but low specificity. The efficacy was classified into five grades: "Excellent", "Good", "Moderate", "Equivocal", and "Poor". 67.3% of all examination were evaluated as "Excellent" or "Good". This study revealed TCK-17 was a useful radiopharmaceutical for lymphoscintigraphy because of its safety and effectiveness. PMID- 1434089 TI - Facilitatory and inhibitory processes in the thalamic ventrobasal nucleus of the rat. AB - Experiments were carried out on anesthetized rats to clarify the actions of the corticothalamic input on the thalamic ventrobasal neuron (VB). The field potentials and the unit activities were evoked in the VB by the electrical stimulation of the contralateral (cSCx) and ipsilateral somatosensory cortex (SCx), the thalamic radiation (TR), and the medial lemniscus (ML). The corticothalamic axons could be activated from cSCx via the ipsilateral SCx, with the result of a clear excitation followed by the inhibition of VB neurons. These VB responses were also evoked from SCx, TR, or even ML with other responses. Paired stimulation of these sites revealed that the corticothalamic input exerted facilitation on the succeeding corticothalamic input for 690 +/- 74.2 ms (n = 5). It was confirmed that these corticothalamic actions were abolished by the lesion of SCx. In contrast to the corticothalamic-induced VB responses, the VB responses to ML input received powerful inhibitory effects from ML or SCx for 1,150 +/- 35.4 ms (n = 5). It is concluded that the corticothalamic input can excite the VB neuron in a mechanism that differs from that of ML input. PMID- 1434088 TI - [Clinical usefulness of exercise/rest 99mTc-teboroxime SPECT imaging: results of a Japanese multi-center phase II study]. AB - 99mTc-Teboroxime [Chloro[tris(cyclohexyldioxime)methaneboronic acid] (99mTc)technetium], a perfusion agent for myocardial imaging, has a distinct advantage over 201Tl because of its very high myocardial extraction and is a 99mTc compound ideal for gamma camera imaging. This agent also demonstrates rapid myocardial washout, which allows completion of exercise and rest imaging studies in a short interval (to 1 hour). However, the rapid washout necessitates the completion of image acquisition very quickly after injection and therefore may require nonconventional SPECT imaging. In this Phase II study we evaluate the safety and efficacy of 99mTc-Teboroxime to detect coronary artery disease by exercise and rest SPECT imaging in 38 patients with prior myocardial infarction, 31 patients with angina pectoris, and 4 patients with non-coronary cardiac diseases. The 99mTc-Teboroxime dose used was 370-740 MBq in each study. The findings were compared with coronary angiography or 201Tl exercise and redistribution SPECT. No significant adverse reactions or laboratory abnormalities attributable to 99mTc-Teboroxime were observed. The quality of SPECT images was optimal in 62.5% of all patients. The relatively large population of suboptimal cases (37.5%) was attributed to the delay of the start and prolongation of the image acquisition time. In 85.7% of patients whose imaging was started within 5 minutes and completed within 11 minutes after injection, optimal quality was observed. Thus, 99mTc-Teboroxime SPECT requires the rapid completion of image acquisition after injection to achieve optimal image quality. Abnormalities of 99mTc-Teboroxime distribution were detected in 97.1% and 62.1% of patients with prior myocardial infarction or angina pectoris, respectively. The concordance with coronary angiography was 84.4% and 68.0%, and with 201Tl was 78.1% and 74.1%, respectively. Although standardization of the image protocol suitable for this agent is needed for the next study, these high correlations suggest the potential usefulness of 99mTc-Teboroxime SPECT imaging. PMID- 1434090 TI - Reappraisal of the corticothalamic and thalamocortical interactions that contribute to the augmenting response in the rat. AB - In urethane-anesthetized rats, low frequency electrical stimulation of the thalamic radiation (TR) evoked an augmenting response in the somatosensory cortex (SCx) which was followed by rhythmic slow waves. The augmenting response mainly consists of the incremental secondary response (II-response). Simultaneously, augmentation also occurs in the ventrobasal nucleus of thalamus (VB) on the late component responses, C- and D-waves, to TR stimulation. The latencies of these augmented responses were shorter for the C-wave and the accompanying unit discharges in the VB relay neurons than for the D-wave and the II-response. We hypothesized that the thalamo-cortico-thalamic reverberating circuit was crucial in generating the augmenting response in the SCx. To test this hypothesis, an attempt was made to block temporarily the corticothalamic glutamatergic transmission by means of microinjections of kynurenate (KYN), an antagonist of glutamate, into the VB with a dose of more than 2 mM. This local procedure blocked all of the augmenting phenomena completely with a full recovery after the duration that depended on the dose of KYN. Besides, in the stage of complete blocking of the II-response to the test TR stimuli, the augmentation was able to be restored by adding a short train of high frequency TR stimuli that mimicked a burst discharge of VB relay neurons. These results in support of the hypothesis would reappraise the functional significance of the reverberating circuit in augmentation that has recently been controversial. PMID- 1434091 TI - Effects of blood gas, pH, lactate, potassium on the oxygen uptake time courses during constant-load bicycle exercise. AB - Changes in the time courses of VO2 during constant-load exercise were examined in connection with other cardiorespiratory and blood chemical parameters. Eleven healthy male subjects performed a ramp exercise and three to six constant-load exercises at varying degrees of load using an electro-braked bicycle ergometer. Heart rate, ventilation, and gas exchange were measured during both types of exercise, and chemical parameters of the subject's blood (blood gas, pH, lactate, and electrolytes) were determined during two intensities of constant-load exercise. The time courses of cardiorespiratory and blood chemical data 3 min after the onset of constant-load exercise were fitted by linear regressions to see whether these parameters had reached the steady state or not. Heart rate increased significantly at a lower intensity of constant-load exercise than VE, VO2, and VCO2. While the increase in VCO2 was slower than that of VO2, a definite difference in time courses was not found between VE and VO2. The time courses of changes in blood gas, pH, bicarbonate, and lactate were not correlated with those of VO2. However, changes in blood potassium concentration were closely correlated with those of VO2 in terms of time courses and magnitude. This suggests the possibility that blood potassium may play an important role in the control of VO2 time course during constant-load exercise. PMID- 1434092 TI - Responses of muscle sympathetic nerve activity and cardiac output to the cold pressor test. AB - We measured muscle sympathetic nerve activity (MSA) to clarify the mechanisms of the blood pressure rise during cold pressor test (CPT), simultaneously with impedance cardiography and blood pressure wave measurement in 10 healthy subjects. MSA remained unchanged during the initial period of 0-30s of the CPT and increased remarkably during the later period of 30-90s of the CPT, while cardiac output exhibited a slight increase during the initial period but not during the later period. Mean blood pressure increased significantly throughout the entire period of CPT and reached the maximal level during 90-120s of the CPT. The mean blood pressure and total peripheral resistance during the CPT showed a linear correlation with MSA. In conclusion, an increase of cardiac output elevates blood pressure at the initial period of the CPT with little increase in MSA, while an increase of MSA plays an essential role to elevate the blood pressure at the later period of the CPT. PMID- 1434093 TI - ANP decreases arterial oxygen partial pressure by increasing shunt flow in pulmonary circulation. AB - This study was designed to clarify the decreased arterial oxygen partial pressure (PaO2) mechanism induced by atrial natriuretic peptide (ANP) infusion. In order to examine the effects of ANP on gas exchange across the normal lungs, ANP was infused to eight anesthetized dogs, ventilated with mixed gases of oxygen and nitrogen. PaO2 and venous oxygen partial pressure (PvO2), ventilation-perfusion ratio (VA/Q), shunt-total blood flow ratio (QS/QT) were measured before and during ANP infusion under ventilation with 10, 20, 30% oxygen. In this study ANP decreased PaO2 from 89.0 +/- 4.2 to 85.4 +/- 5.4 mmHg during 20% oxygen ventilation, and from 138.1 +/- 3.6 to 132.5 +/- 4.1 mmHg during 30% oxygen ventilation. ANP increased VA/Q and QS/QT. We conclude that the decrease in PaO2 caused by ANP infusion was mainly due to the increased venous admixture. PMID- 1434094 TI - Excitatory and inhibitory controls of the masseter and temporal muscles elicited from teeth in the rat. AB - The periodontal mechanism that controls the jaw reflexes was examined in lightly anesthetized rats. Motor-unit activity in the masseter and temporal muscles was recorded electromyographically and pressure stimulation was applied to either an upper incisor or an upper molar. Reflex effects of dental stimulation varied depending on the level of ongoing activity (background activity, BGA) in each motor unit. Incisal or molar stimulation elicited excitatory reflexes in both the masseter and temporal motor units at a low BGA, but inhibitory reflexes in both types of motor unit at a higher BGA. In contrast to these synergistic reflex actions, the reciprocal reflex actions of the two motor units that belonged to the respective muscles occurred when the BGA was intermediate. The results suggest that different patterns of periodontal jaw reflexes may be elicited, depending on the different levels of BGAs. Furthermore, the present reflexes were modified with the site of a stimulated tooth within the dentition. Incisal stimulation produced greater excitation in the masseter motor unit than in the temporal one, and the opposite type of response occurred during molar stimulation. Moreover, smaller-amplitude motor units with a low reflex threshold and larger-amplitude motor units with a higher reflex threshold tended to exhibit excitatory and inhibitory reflexes, respectively. PMID- 1434095 TI - Effect of immobilization stress on in vitro and in vivo thermogenesis of brown adipose tissue. AB - Repetitive intermittent stress such as immobilization has been shown to induce an improved cold tolerance through an enhanced capacity of nonshivering thermogenesis (NST), causing positive cross adaptation between nonthermal stress and cold. In the present study, effect of 3-h-daily immobilization stress for 4-5 weeks was investigated on in vitro and in vivo thermogenesis of interscapular brown adipose tissue (BAT). In vitro thermogenesis was measured in the minced tissue blocks incubated in Krebs-Ringer phosphate buffer with glucose and albumin at 37 degrees C, using a Clark-type oxygen electrode. The stressed rats showed less body weight gain during the experiment. The BAT weight, its protein and DNA contents were significantly greater in the stressed rats. Basal, noradrenaline- and glucagon-stimulated oxygen consumptions were significantly greater in the stressed rats. In vivo thermogenesis was assessed by the changes of temperatures in colon (Tcol), BAT (TBAT), and tail skin (Tsk) induced by noradrenaline or glucagon infusion in the anesthetized rats. Noradrenaline and glucagon increased the TBAT and the extent of increase was greater in the stressed rats. These results indicate that cross adaptation between nonthermal stress and cold may be mediated through an enhanced thermogenic activity of BAT. PMID- 1434096 TI - Effects of selective vagal stimulation on the gallbladder and sphincter of Oddi and peripheral vagal routes mediating bile evacuative responses induced by hypothalamic stimulation. AB - Peripheral routes of the vagus nerves to the biliary system were studied in anesthetized dogs using various selective vagal stimulation. Efferent stimulation of the gastric, hepatic, or celiac vagal branch as well as the cervical or thoracic vagal trunk induced gallbladder and Oddi's sphincter contractions, but those induced by hepatic vagal stimulation were rather small. The contraction responses in the gallbladder and sphincter of Oddi induced by thoracic vagal stimulation were greatly reduced after an external ligation around the pyloric sphincter. After administration of sympathetic blockers and atropine, vagally induced gallbladder contractions were completely abolished and slight relaxation was seen in some animals. On the other hand, relaxation or transient relaxation followed by enhanced contractions was elicited in the sphincter of Oddi by vagal stimulation after atropine and sympathetic blockers. The relaxation response in the gallbladder after atropine and sympathetic blockers was abolished and that in the sphincter of Oddi was greatly reduced after the ligation around the pyloric sphincter. Stimulation of a ventral part of the anterior hypothalamic area induced gallbladder contraction and simultaneous relaxation of the sphincter of Oddi. These responses were completely abolished by the ligation around the pyloric sphincter in six dogs, while a slight relaxation response in the sphincter of Oddi remained in two dogs. These results suggest that the vagal fibers passing across the pyloric sphincter region are important for regulation of canine biliary motility and that extragastric vagal routes play a minor role in the nervous control of canine bile evacuation. PMID- 1434097 TI - Nitroarginine-sensitive and -insensitive components of the endothelium-dependent relaxation in the guinea-pig carotid artery. AB - In the guinea-pig carotid arteries, nitroarginine elevated the resting tension (greater than 3 x 10(-6) M) and enhanced the noradrenaline (NA)- and high potassium (high-K, 29.6 mM) induced contractions (greater than 10(-7) M), in a concentration-dependent manner, with no significant change in the resting membrane potential and depolarizations elicited by NA or high-K. ACh (10(-6) M) relaxed the muscles precontracted with NA or high-K by 96 or 46% of the contraction, respectively. In the presence of nitroarginine (10(-5) M) for 1-3 h, the ACh-induced relaxation was reduced to 40 or 0% of the NA- or high-K contractions, respectively. In tissues contracted with NA and exposed to nitroarginine, the ACh-induced relaxation changed from a sustained to a transient form. ACh relaxed the muscles to a similar extent, at any given level of tension, as elevated by different concentrations of NA to 1-3 times the level produced by 10(-6) M NA, either in the presence or absence of nitroarginine. ACh (greater than 10(-8) M) produced a transient hyperpolarization of the membrane, in an endothelium-dependent manner, and the responses were blocked by atropine (10(-6) M) or high-K solution, but not by NA or nitroarginine. We propose that 1) endothelium-derived hyperpolarizing factor (EDHF) is produced by pathways independent of the biosynthesis of endothelium-derived relaxing factor (EDRF), 2) the sustained release of EDRF maintains the muscle tone at a low level, and 3) the endothelium-dependent relaxation is produced by both EDRF and EDHF, and they elicit sustained and transient relaxations, respectively. PMID- 1434098 TI - Effects of brain natriuretic peptide and C-type natriuretic peptide infusion on urine flow and jejunal absorption in anesthetized dogs. AB - Effects of brain natriuretic peptide (BNP) or C-type natriuretic peptide (CNP) on urinary excretion and jejunal absorption of fluid and electrolytes were examined in anesthetized dogs. Intravenous infusion of BNP increased urinary fluid and electrolyte excretion and decreased jejunal fluid and electrolyte absorption. CNP had a similar effect on jejunal absorption as BNP. However, CNP had no significant effect on renal fluid or electrolyte excretion. These results indicate that: 1) BNP is a powerful natriuretic peptide comparable to ANP and; 2) CNP may also contribute to the regulation of body fluid homeostasis by way of inhibiting net jejunal fluid and electrolyte absorption. PMID- 1434099 TI - Peristaltic movement evoked in intestinal tube devoid of mucosa and submucosa. AB - Computerized analysis of video-recorded peristalsis was made in a preparation of guinea-pig ileum tube from which both mucosa and submucosa were mechanically scraped off. Threshold value for provoking peristalsis was higher, conduction velocity of peristalsis was slower, and peristaltic force was weaker in comparison with the ileum tube from which only mucosa was scraped off and with the normal ileum tube. A histological control of the preparation proved that there was no nerve cell body of submucous plexus on the surface of separated circular muscle. It was concluded that peristalsis, though impaired, could be provoked by way of activation of the reflex arch consisted by neural circuit of myenteric neurons which should be produced by excitation of stretch receptors in the muscularis externa. PMID- 1434100 TI - Pulmonary C-fibers do not play a role in ammonia-induced brief tachypnea in the rabbit. AB - To determine the role of pulmonary C-fibers in evoking a brief tachypnea induced by ammonia vapor, we examined the responses of diaphragm electromyogram (DIAP EMG) to ammonia inhalation before and after procaine treatment to the contralateral vagus nerve in urethane-anesthetized, spontaneously breathing rabbits with unilateral vagotomy. Procaine treatment that blocked the conduction of vagal afferent C wave did not significantly alter the response of brief tachypnea to ammonia. Furthermore, the stimulation of pulmonary C-fibers by ammonia inhalation did not coincide with the induction of brief tachypnea. In addition, we also examined the responses of rapidly adapting receptors (RARs) and slowly adapting receptors (SARs) to ammonia inhalation in rabbits, particularly in which inhalation of this chemical gas produced a brief tachypnea. The burst activity of RARs evoked by ammonia inhalation coincided with the phase of rapid shallow breathing for a few breaths. The discharge rates of SARs during both inspiration and expiration increased when ammonia inhalation caused a brief tachypnea. From these results, it can be suggested that the ammonia-induced brief tachypnea is probably mediated by transient stimulation of both SAR and RAR activities but does not occur as a result of the pulmonary C-fiber stimulation. PMID- 1434101 TI - Acid-induced two-step depolarization in the peritubular membrane of bullfrog kidney proximal tubules. AB - Using ion-selective microelectrode technique, we investigated acid-induced changes of peritubular membrane potential (EM) and intracellular activity of Na+ and H+ ((Na)i and pHi) in the proximal tubule of perfused bullfrog kidney in vivo. When peritubular pH was reduced at constant PCO2, EM was depolarized in two steps: i.e., an initial sharp fall followed by an additional deeper fall. This was termed as the acid-induced two-step depolarization. During this change, pHi was decreased gradually from 7.4 to 6.9 in response to 1/10 HCO3- reduction (pH from 7.7 to 6.7), whereas (Na)i was increased after a transient decrease. This result supports the peritubular rheogenic HCO3- exit coupled to Na+ movement during the initial depolarization period. Complete removal of peritubular HCO3- at constant pH produced a less marked initial depolarization with a transient rise of pHi, followed by a partial repolarization without appreciable change in (Na)i. Peritubular SITS administration inhibited these depolarization responses to the acid perfusion. The above findings suggest that 1) the initial part of the two-step EM depolarization produced by low HCO3- or HCO(3-)-free perfusion resulted mainly from the peritubular rheogenic exist of HCO3-, 2) the magnitude of initial depolarization would also be affected by pHi, and 3) the subsequent delayed changes of EM were mainly determined by the pHi-sensitive K+ conductance of the peritubular membrane. PMID- 1434102 TI - Forced vital capacity in Malaysian females. AB - Spirometry was performed on 614 female subjects ranging in age from 13 to 69 years and comprising all the main races in Malaysia. They were divided into six age categories. Mean forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were 2.51 +/- 0.02 and 2.31 +/- 0.02l, respectively. Both FVC and FEV1 correlated negatively with age. Regression analysis revealed an age-related decline in FVC of 220 ml per decade of life. Multiple stepwise regression of the data for the prediction of an individual's FVC above the age of 20 years gave an equation: FVC(l) = 0.0312 (height)-0.022 (age)-1.64. Predicted FVC values derived from equations based on other populations were considerably higher than the observed mean in this study. Our study, therefore, reemphasizes the need to be cautious when applying formulae derived from one population to another. Grossly erroneous conclusions may be reached unless predicted equations for lung-function tests for a given population group are derived from studies based on the same population group. PMID- 1434103 TI - Ca(2+)-activated K+ channel is present in guinea-pig but lacking in rat hepatocytes. AB - The mechanisms of norepinephrine-induced membrane responses in isolated hepatocytes from guinea-pigs and rats were compared using the suction-pipette, patch-clamp method, and intracellular Ca2+ concentration ([Ca2+]i) was measured using the Ca2+ fluorescent dye, Quin 2. The resting membrane potentials of isolated guinea-pig hepatocytes were -50 +/- 1 mV (mean +/- SD; n = 38), which is similar to that previously reported in rat hepatocytes by Sawanobori et al. (J Cell Physiol 139: 580-585, 1989). In guinea-pig hepatocytes, norepinephrine (6 microM) caused a membrane hyperpolarization, and norepinephrine (6 microM) or Ca(2+)-ionophore (A23187) (0.4 microM) caused a corresponding outward current. The sensitive current produced by norepinephrine and Ca(2+)-ionophore reversed its polarity at -74 +/- 9 mV (n = 7). The single channel recorded by cell attached patch and inside-out patch had mean conductance of around 20 + 1 pS and was activated by 1 microM [Ca2+]i. On the other hand, neither norepinephrine (6 20 microM) nor Ca(2+)-ionophore (A 23187) (0.4 microM) caused any change in membrane potential and current in rat hepatocytes, whereas norepinephrine increased [Ca2+]i both in rat and guinea-pig hepatocytes to a similar degree. In the single-channel recording, we recorded single channels that had a mean conductance of 109.8 +/- 17.7 pS different from around 20 pS in guinea-pig. In inside-out patches, increased Ca2+ concentration from 10(-6) to 10(-3) M at the intracellular face of the membrane did not modify the single channel of rat hepatocytes. These results indicate that increased [Ca2+]i activates this channel in guinea-pigs, but that the channel activated by increased [Ca2+]i is lacking in rat hepatocytes membrane. Therefore, different mechanism operates in different species of liver cells to keep the constant state. PMID- 1434104 TI - Transient increase in deformability of stressed red blood cells and role of plasma proteins. AB - In the context of possible fatigue and eventual destruction of red blood cells (RBCs) in the circulation, changes in deformability (filterability) were studied in RBCs which had just undergone deformation. Fresh human RBCs suspended in media of varying protein concentrations were stressed by causing them to pass through a 5-microns Nuclepore filter. Resultant changes in their deformability were assessed from their mean pore passage time in a subsequent filter passage. Contrary to the expectation, that deformability would be reduced, shortened passage times were observed for those stressed RBCs. The changes were, however, transient and, like the initial passage times, were an increasing function of the protein concentration in the suspending fluid. These results appeared to be consistently explicable by assuming release due to stresses and readsorption in time for plasma protein molecules normally adsorbed on cell surfaces. An analysis, furthermore, yielded acceptable estimates for magnitude of the cell plasma protein interaction, number of protein molecules normally adsorbed on a cell, and also cell membrane viscosity and its apparent change due to the protein adsorption. PMID- 1434105 TI - Frequency thresholds of rat cochlear nerve fibers. AB - Activities of single cochlear nerve fibers of Wistar rats were recorded extracellularly. Best frequencies (BF) distributed from 0.50 to 62.6 kHz. The audiogram was made as the minimum boundary of the BF threshold distribution. The range of audible frequency was 0.54-63 kHz at 60 dB SPL and 0.15-67 kHz at 100 dB SPL. The lowest trough of the audiogram was 5 dB SPL at 41.2 kHz. There was the second trough of 10 dB SPL at 7.01 kHz leaving a notch between the two troughs. The shapes of the frequency-threshold curves (FTCs) of fibers were evaluated quantitatively and typical FTCs were shown as a function of BF. PMID- 1434106 TI - Muscle activity during forelimb stepping in decerebrate cats. AB - In decerebrate cats with the lower thoracic cord transected, electromyographic activities were analyzed in up to 41 forelimb muscles, almost all muscles involved in forelimb stepping (intrinsic hand muscles were not included). From the active period in the step cycle, muscles were classified into three groups: extensors, of which activity is like that of elbow extensors; flexors, activity like that of elbow flexors; others, including dorsiflexors of the wrist, pronators, and supinator. The results were well consistent with those from conscious animals as well as efferent pattern of fictive locomotion in elbow and distal muscles. Nevertheless, in some proximal muscles discrepancies were noted, suggesting their changeability depending on environmental conditions. Recording from almost all muscles allowed to estimate rhythmic change of the overall output of the forelimb central pattern generator. PMID- 1434107 TI - Activity of cervical neurons during forelimb fictive locomotion in decerebrate cats. AB - Unit activities were recorded from cervical neurons during forelimb fictive locomotion. Rhythmic activities were evaluated by onset and termination. Rhythmically-active neurons were classified into 4 major groups: (1) neurons, the active periods covered the whole flexor phase; (2) f+e neurons, the active periods commenced prior to and terminated in the extensor phase; (3) e neurons, the active periods appeared within the extensor phase; (4) e+f neurons, the active periods commenced prior to and terminated in the flexor phase. In addition, a few neurons that were not classified were observed. Neuronal behaviors seemed to suggest that and e+f were grouped "flexor-like," while e and f+e were grouped as "extensor-like." "Flexor-like" neurons were likely distributed in the dorsal (lamina V-VI) and rostral (C5-C6) region, whereas "extensor-like" neurons distributed mainly in the ventral (lamina VI-VII) and caudal (C7-T1) region. Some neurons showed rhythmic activities prior to appearance of fictive locomotion (prelude rhythm). The structure of the central pattern generator was discussed. PMID- 1434108 TI - Hypothalamic corticotropin-releasing hormone (CRH) secretion into hypophysial portal blood is regulated by cutaneous sensory stimulation in anesthetized rats. AB - The effects of noxious and non-noxious mechanical stimulation of various segmental skin areas (face, forelimb and forepaw, abdomen, hindlimb and hindpaw) on the secretion of immunoreactive corticotropin-releasing hormone (iCRH) from the hypothalamus into hypophysial portal blood was examined in artificially ventilated rats under halothane anesthesia. Secretion of iCRH was calculated from the iCRH concentration in hypophysial portal plasma and the plasma flow rate. Noxious mechanical stimulation of the skin was delivered by pinching using surgical clamps, while non-noxious mechanical stimulation was provided by brushing with tooth brushes. Pinching of the bilateral forepaws or hindpaws and brushing of the bilateral hindlimbs for 20 min increased hypothalamic iCRH secretion. In contrast, pinching of the face or abdomen and brushing of the face, forelimbs, or abdomen for 20 min did not significantly influence it. These results indicate that cutaneous mechanical sensory stimulation contributes to the reflex regulation of CRH secretion from the hypothalamus into hypophysial portal blood, and also that this effect is highly dependent on the site of stimulation. PMID- 1434109 TI - Intracellular and extracellular chloride ions in the horizontal cells of the stingray retina. AB - Intracellular and extracellular concentrations of chloride ([Cl-]i, [Cl-]o) ions in the horizontal cells of the stingray retina were studied by means of ion selective microelectrodes. The electrodes used were of the double-barreled type and Corning's #477315 resin was used as the exchanger. The average [Cl-]o and [Cl ]i in the L-type cells were 320 and 130 mM, respectively (n = 37), and the equilibrium potential (ECl) was calculated as -23.3 mV. In some cases, dark membrane potentials were more positive than the ECl. With white light stimulus, the membrane hyperpolarized to a more negative level than ECl. Based on the experiments described above, the hypothesis that the hyperpolarizing response of horizontal cells is due to the permeability change of the membrane to chloride ion was excluded in the stingray retina. PMID- 1434110 TI - Effects of KB-2796, a new diphenylpiperazine calcium antagonist, on renal hemodynamics and urine formation in anesthetized dogs. AB - The effects of KB-2796, a new calcium antagonist with a diphenylpiperazine moiety, on renal hemodynamics and urine formation were investigated in anesthetized dogs. Intravenous infusion of KB-2796 (10, 30, and 100 micrograms/kg/min) decreased mean blood pressure (MBP) and renal vascular resistance (RVR) in a dose-dependent manner, but did not change renal blood flow (RBF). At the highest dose, glomerular filtration rate (GFR) and urine flow (UF) tended to decrease. Nicardipine (0.1, 0.3, and 1 microgram/kg/min) also dose dependently decreased MBP, RVR, GFR, and UF. When KB-2796 was infused into the renal artery at lower doses of 3 and 10 micrograms/kg/min, UF and urinary excretion of electrolytes increased without a significant change in RBF and GFR. Intrarenal infusion of KB-2796 at 30 micrograms/kg/min and nicardipine at 0.3 microgram/kg/min produced a significant increase in GFR, RBF, UF, urinary excretion of electrolytes, and renin secretion rate. These results suggest that KB-2796 administered intrarenally exerts a diuretic action via tubular effects and the alteration of renal hemodynamics. However, its diuretic action might be masked by diminished urine formation via a reflex activation of the sympathetic nerves and/or via a reduction of renal perfusion pressure when it is administered systemically. PMID- 1434111 TI - Stimulation by capsaicin of gastric alkaline secretion in anesthetized rats. AB - Effects of mucosal application of capsaicin on alkaline secretion were examined in the stomachs of anesthetized rats and compared with those in the duodenum. The stomach (acid secretion was inhibited by omeprazole given i.p.) or the duodenum was perfused with saline (pH 4.5); both the pH of the perfusate and transmucosal potential difference (PD) were continuously monitored; and the HCO3- output was determined by the pH change. Under these conditions, the mucosal application of capsaicin (0.3-6 mg/ml for 30 min) caused significantly increased pH and HCO3- output in a concentration-related manner in both tissues, while PD increased in the duodenum and decreased in the stomach. The HCO3- stimulatory action of capsaicin was markedly attenuated by sensory deafferentation, significantly mitigated by prior administration of indomethacin, and exhibited a marked tachyphylaxis after the repeated exposure at a high concentration (6 mg/ml). None of these treatments had any effect on the pH, PD and HCO3- responses induced by prostaglandin E2 (300 micrograms/kg, i.v.) in these tissues. These results indicate that mucosal application of capsaicin increased the gastroduodenal HCO3- output by stimulation of capsaicin-sensitive sensory neurons. This action may be in part mediated by endogenous prostaglandins. PMID- 1434112 TI - Studies on the antinephritic effect of plant components (4): Reduction of protein excretion by berberine and coptisine in rats with original-type anti-GBM nephritis. AB - The present study was conducted to investigate the antinephritic effects of berberine and coptisine, which are contained in Coptidis rhizoma, on original type anti-GBM nephritis in rats. Berberine and coptisine at the doses of 0.5, 1.0 and 5.0 mg/kg/day, i.p. were effective in inhibiting urinary protein excretion, elevation of serum cholesterol and creatinine contents as well as glomerular histopathological changes. In addition, berberine at 20 mg/kg/day, p.o. also inhibited urinary protein excretion throughout the experimental periods. Berberine and coptisine inhibited platelet aggregation in both in vitro and in vivo assays, and berberine inhibited the decline of renal blood flow. Although berberine inhibited an increase in thromboxane B2 formation, it increased the formation of 6-keto-prostaglandin F1 alpha in platelets and isolated glomeruli. These results indicate that the antinephritic effects of berberine and coptisine may be partly due to antiplatelet action and improved renal hemodynamics via changing prostanoid synthesis. PMID- 1434113 TI - Effects of semotiadil (SD-3211), a benzothiazine calcium antagonist, on blood pressure and atrioventricular conductivity in anesthetized dogs. AB - We investigated the effects of semotiadil (SD-3211), a novel calcium antagonist, on blood pressure and the atrioventricular (AV) conduction time and functional refractory period (FRP) of the AV conduction system (AV conductivity) in anesthetized open-chest dogs. The heart was electrically stimulated at a constant rate. In dogs with an intact nerve supply to the heart, i.v.-injections of semotiadil (0.03 to 0.3 mg/kg) produced a fall of blood pressure in a dose dependent manner. AV conduction time and FRP were prolonged by rather higher doses (0.3 mg/kg), and second-degree AV block occurred only with the highest dose (1 mg/kg). In dogs with the nerve supply to the heart interrupted, the vasodepressor effects and suppressant effects of semotiadil on AV conductivity were slightly enhanced. The suppressant effects on AV conductivity became marked as pacing rates were increased. These results suggest that semotiadil at appropriate doses produces a vasodepressor effect without affecting AV conductivity even in the heart deprived of nervous control, e.g., the heart with beta-adrenoceptors blocked. The frequency-dependent suppressant effect on FRP of semotiadil is also noteworthy in the treatment of reentrant supraventricular tachycardia that involves the AV node. PMID- 1434114 TI - Inhibitory action of dilazep on histamine-stimulated cytosolic Ca2+ increase in cultured human endothelial cells. AB - Using a fluorescent Ca(2+)-sensitive dye, fura-2, and photometric fluorescence microscopy, we measured changes in cytosolic Ca2+ concentration ([Ca2+]i) in cultured human endothelial cells and studied the effect of dilazep on [Ca2+]i elevation induced by histamine. Histamine (1 microM) caused a rapid transient peak in the average [Ca2+]i of a group of cells (approximately 10(2) cells), followed by a decrease to a sustained elevation. Dilazep as well as diltiazem (1.0 to 100 microM) concentration-dependently inhibited the latter sustained elevation, which was eliminated by removal of extracellular Ca2+, while the initial transient response was not changed by dilazep at concentrations up to 100 microM. The IC50 values of dilazep and diltiazem were 16 and 58 microM, respectively. The patterns of the [Ca2+]i elevation responses to histamine were variable among individual cells. Some single cells showed a transient peak and a sustained elevation as observed in a group of cells. Some single cells caused a repetitive spikelike elevation of [Ca2+]i. Dilazep lowered the sustained elevation to the resting level and in some single cells, changed the sustained elevation to the spikelike elevation. The frequency of the spikelike [Ca2+]i elevation was also decreased by dilazep. Decrease in extracellular [Ca2+] showed the same pattern of inhibitory actions as dilazep did. These results indicate that dilazep inhibits the extracellular Ca2+ influx in endothelial cells. PMID- 1434115 TI - Myocardial Na+ during ischemia and accumulation of Ca2+ after reperfusion: a study with monensin and dichlorobenzamil. AB - The intracellular cation contents were determined in isolated perfused rat heart using cobaltic EDTA as a marker of the extracellular space. In hearts in which Na+ accumulation was induced with monensin, a Na+ ionophore, during 20 min ischemia which otherwise did not result in accumulation of Na+, the levels of Na+ and Ca2+ were significantly higher after reperfusion with a significant decrease in K+. While the recovery of the cardiac mechanical function (CMF) was complete after reperfusion in control hearts, the recovery was incomplete in monensin hearts. Dichlorobenzamil (DCB), the most specific inhibitor of Na(+)-Ca2+ exchanger, infused for 10 min before induction of ischemia in a dose of 10(-5) M, which produced a definite suppression of CMF (over 80%), inhibited the accumulation of Ca2+ and Na+ and the loss of K+ and ATP after 40 min-ischemia and reperfusion. The same dose of DCB given for 3 min before induction of ischemia and after reperfusion, which produced a less than 20% inhibition of CMF, failed to prevent the Ca2+ accumulation after 40 min-ischemia and reperfusion. These findings are at variance with the idea that the accumulation of Na+ during ischemia and the consequent augmented operation of Na(+)-Ca2+ exchange is responsible for accumulation of Ca2+ after reperfusion. PMID- 1434116 TI - Active cutaneous anaphylaxis (ACA) in the mouse ear. AB - Active cutaneous anaphylaxis (ACA) was studied in the ear of female BALB/c mice. Mice were immunized with ovalbumin in the presence of aluminium hydroxide gel or complete Freund's adjuvant (CFA). Two weeks after the immunization, ACA was elicited in the mouse ear by injecting 10 microliters of antigen solution intradermally into the ear lobe. ACA was assessed by the amount of extravasated dye, which was given intravenously just after the antigen injection. Antiallergic drugs (tranilast, ketotifen and azelastine), antihistamines (chlorpheniramine, diphenhydramine and mequitazine), beta-stimulants (isoproterenol and salbutamol), theophylline and glucocorticoids (hydrocortisone, prednisolone and dexamethasone) inhibited the reaction significantly. These drugs inhibited both ACA in mice immunized with alum-precipitated antigen and ACA in mice injected with CFA emulsified antigen similarly. ACA in the mouse ear might be a useful tool for studying drugs for allergy. PMID- 1434117 TI - Influence of DOCA treatment on administration-time-dependent changes in the effects of furosemide in saline-loaded rats. AB - We have previously found that the administration-time-dependent change in the effects of furosemide, a loop diuretic agent, is observed in normal rats. The present study was undertaken to examine whether an alteration in this phenomenon occurs in rats with DOCA-saline hypertension. Unilateral nephrectomized rats were divided into three groups. The first group (DOCA-saline) received a 50 mg DOCA tablet intraperitoneally and drank 1% NaCl solution. The other two groups were given sham operations. A 1% NaCl solution was given as drinking water to the second group (control-saline), while tap water was given to the third group (control-water). Furosemide (30 mg/kg) was given orally to each group at 12 a.m. or 12 p.m. Urine was collected for 8 hours after the agent, and urinary excretion of sodium and furosemide were determined. Urine volume and urinary excretion of sodium and furosemide following the agent were significantly greater at 12 a.m. than at 12 p.m. in the control-water and control-saline groups. However, the administration-time-dependent changes in these parameters disappeared in the DOCA saline rats. These results suggest that the mode of the administration-time dependent changes in the effects of furosemide is altered in the DOCA-saline hypertensive rats. PMID- 1434118 TI - Vagal afferent fibers and peripheral 5-HT3 receptors mediate cisplatin-induced emesis in dogs. AB - The involvement of visceral afferent fibers and 5-HT3 receptors in the emesis induced by cisplatin was studied in beagle dogs. The emesis induced by cisplatin (3 mg/kg, i.v.) was inhibited by the intravenous administration of ICS205930 (2 x 0.01 or 2 x 0.1 mg/kg) and MDL72222 (2 x 0.5 mg/kg), 5-HT3 receptor antagonists, but not by the intravenous administration of metoclopramide (2 x 0.5 mg/kg), a dopamine D2 receptor antagonist. The cisplatin-induced emesis was also suppressed by the intravenous administration of para-chlorophenylalanine (300 mg/kg/day for 3 days), an inhibitor of 5-HT synthesis. On the other hand, the administration of ICS205930 into the IVth ventricle (2 x 0.01 mg/animal) had no effects on the cisplatin-induced emesis. The cisplatin-induced emesis was completely inhibited by abdominal vagotomy and splanchnicectomy, but not by splanchnicectomy alone. On the contrary, the emesis induced by apomorphine was suppressed by the intravenous (0.1 mg/kg) or intracerebroventricular (0.05 mg/animal) administration of metoclopramide, but not by visceral nerve section. These results strongly suggest that cisplatin evokes emesis mainly by acting on the vagal afferent terminals through the release of 5-HT and that peripheral 5-HT3 receptors are involved in this action. PMID- 1434120 TI - Effect of endothelin (ET)-1, ET-3 and ET-(16-21) on the isolated and perfused rat kidney from normotensive and spontaneously hypertensive rats. AB - We have investigated the effect of endothelin (ET)-1, ET-3 and ET-(16-21) on isolated and perfused rat kidney (IPK). ET-1 and ET-3 produced a similar dose dependent increase in perfusion pressure of IPK, while ET-(16-21) was completely inactive. The ET-1 effects were greater in spontaneously hypertensive rats (SHR) as compared to normotensive rats (WKYR), whereas the ET-3 effects were greater in the SHR group only at the lowest doses. The pressure response of IPK induced by ET-1 was partially modified by prior application of the nitric oxide synthetase inhibitor L-nitroarginine in both WKYR and SHR. PMID- 1434119 TI - Recombinant human tumor necrosis factor-beta entrapped in liposomes formed by a modification of the dehydration-rehydration method retains potent cytotoxic activity on L929 cells in vitro. AB - Recombinant human tumor necrosis factor-beta (rhTNF-beta) may be encapsulated with high efficiency in phosphatidylcholine and distearoylphosphatidylcholine liposomes, with entrapment values of 93.4% and 92.3%, respectively, by first entrapping the substance in multilamellar vesicles using a high solute-to phospholipid ratio followed by freeze-drying and then rehydration. The entrapped cytokine retains potent cytotoxic activity on L929 cells in vitro, causing 100% cytotoxicity, equal to that of free rhTNF-beta at a concentration of about 5 x 10(-8) g/ml. PMID- 1434121 TI - MK-801 prevents the post-ischemic cerebral hypoperfusion, but not the dysfunction of the vagal baroreflex in dogs. AB - Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, failed to protect the vagal component of reflex bradycardia from 5 min global cerebral ischemia in dogs under pentobarbital anesthesia. On the other hand, MK-801 completely prevented the development of the post-ischemic cerebral hypoperfusion without affecting the cerebral blood flow in sham-operated animals. The results suggest that NMDA receptors may participate in the development of the secondary disturbance of the cerebral circulation, but are not involved in the post-ischemic dysfunction of the baroreflex system. PMID- 1434122 TI - Effect of ketotifen on acute gastric lesions and gastric secretion in rats. AB - Ketotifen, a histamine H1-receptor antagonist and mast cell stabilizer, significantly protected the rat gastric mucosa against lesions induced by necrotizing agents, histamine or compound 48/80. The agent significantly inhibited the basal gastric acid secretion, but had little or no effect on the histamine-stimulated secretion. The mucosal protective effect was observed even at a dose that had little or no effect on gastric acid secretion, suggesting that ketotifen exhibits so-called cytoprotective activity. PMID- 1434123 TI - Effect of manidipine on balloon catheter-induced arterial smooth muscle cell proliferation in spontaneously diabetic GK rats. AB - The inhibitory effect of manidipine, a long acting calcium channel blocker, on vascular smooth muscle cell proliferation was investigated in spontaneously diabetic GK rats with balloon catheter-induced denudation of the carotid artery. Treatment with manidipine at doses of 4.6 and 15.1 mg/kg/day inhibited thickening of the neo-intima in the balloon catheter-injured artery without any effect on blood pressure and lowered the ratio of intima to wall areas and wall to total vascular areas in a dose-dependent fashion. These results suggest that manidipine inhibits an abnormal proliferation of the intima in the carotid artery of spontaneously diabetic rats. PMID- 1434124 TI - Neurotrophic effects of epidermal growth factor on cultured brain neurons are blocked by protein kinase inhibitors. AB - The influences of protein kinase inhibitors, K-252a and staurosporine, on the neurotrophic effects of epidermal growth factor (EGF) were investigated in dissociated cell cultures of the hippocampus and cerebellum of fetal rats. Addition of 1 ng/ml EGF enhanced the survival of cultured neurons of both brain regions. Both K-252a (10-200 nM) and staurosporine (1-100 nM) blocked the survival-promoting effects of EGF in a concentration-dependent manner. These results suggest that activation of protein kinase(s) is involved in the neurotrophic effects of EGF. PMID- 1434125 TI - Preventive actions of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) through increases in the activities of oxygen-derived free radical scavenging enzymes in the gastric mucosa on ethanol-induced gastric mucosal damage in rats. AB - Z-103 at 1 to 25 mg/kg, p.o. prevented 100% ethanol-induced gastric mucosal lesions in a dose-dependent manner. Z-103 at 3 to 25 mg/kg, p.o. significantly elevated gastric mucosal superoxide dismutase (SOD)-like activity 1 hr after its administration to normal rats. In addition, Z-103 at doses (10 and 25 mg/kg, p.o.) which prevented 100% ethanol-induced gastric lesion further increased gastric mucosal SOD-like and glutathione peroxidase (GSH-px) activities elevated by 60% ethanol. Z-103 (10 and 25 mg/kg) significantly inhibited the increase in thiobarbituric acid-reactive substances in gastric mucosa injured by 60% ethanol. The combination with cycloheximide, a protein synthesis inhibitor, completely abolished the prevention of 60% ethanol-induced gastric mucosal lesions and the elevation of both free radical scavenging enzyme activities in the mucosa by Z 103 (10 mg/kg, p.o.). These results suggest that Z-103 may partly protect rat gastric mucosa against ethanol-induced damage by scavenging oxygen-derived free radicals via increases in the synthesis of SOD-like and GSH-px enzymes in the mucosa. PMID- 1434126 TI - Ca2+ influx induced by the agonist U46619 is inhibited by hyperpolarization induced by the K+ channel opener cromakalim in canine coronary artery. AB - The fura-2 microscopic fluorimetric method was used to examine the effects of the thromboxane A2 analogue, U46619, on the force of contraction and intracellular calcium concentrations ([Ca2+]i) in canine coronary arteries. Upon cumulative application, U46619 increased [Ca2+]i and force. Depolarization by 20 mM KCl potentiated the increase in [Ca2+]i and increased the maximum force induced by U46619. In 5 mM KCl-PSS, the reduction of resting [Ca2+]i by cromakalim (3 x 10( 6) M) was greater than that by verapamil (3 x 10(-6) M). Cromakalim and verapamil inhibited the increases in [Ca2+]i and force induced by U46619 in 5 mM KCl-PSS. In 90 mM KCl-PSS in the presence of U46619, verapamil inhibited the increases in [Ca2+]i and force, whereas cromakalim did not inhibit them at all. The inhibitory effect of cromakalim was counteracted by depolarization by 20 or 25 mM KCl. Curves in the presence of U46619 which related force to [Ca2+]i were shifted to the left compared with that in the absence of U46619, suggesting that U46619 increases the Ca(2+)-sensitivity of the contractile proteins. Thus, U46619 produces Ca2+ influx through L-type Ca2+ channels, which are deactivated by hyperpolarization induced by cromakalim. PMID- 1434127 TI - Hypolipidemic effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) in rats. AB - We examined the effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) with high purity on circulating lipids in rats under several experimental conditions. In normolipidemic rats, EPA-E decreased the lipids in a dose dependent manner. Clofibrate (100 mg/kg/day) was more potent in lowering the lipids than EPA-E (1000 mg/kg/day). In high cholesterol diet-fed rats, EPA-E (300 mg/kg/day) decreased the total cholesterol. However, clofibrate (300 mg/kg/day) had little effect on the total cholesterol. In hypertriglycemic rats induced by corn oil, EPA-E (300 mg/kg/day) or clofibrate (100 mg/kg/day) reduced the rise of triglycerides. EPA-E (300 mg/kg/day), clinofibrate (100 mg/kg/day) or clofibrate (300 mg/kg/day) caused a significant reduction in the lipids induced by the injection of Triton WR-1339. Furthermore, EPA-E (300 mg/kg/day) or clinofibrate (100 mg/kg/day) decreased the elevation of lipids produced by feeding the rats a casein-rich diet. These results show that EPA-E possesses potent inhibitory activity on experimental hyperlipidemia induced either exogenously or endogenously. PMID- 1434128 TI - Impairment of endothelium-dependent relaxation in aorta from rats with arteriosclerosis induced by excess vitamin D and a high-cholesterol diet. AB - The present investigation was undertaken to characterize the relaxing responsiveness in aortic strips from rats with arteriosclerosis, which was produced by excess vitamin D2 (VD) administration followed by treatment with or without a high-cholesterol diet for 6 weeks (VD + CHOL and VD group, respectively). This arteriosclerotic aorta was characterized by medial calcification and intimal cell proliferation. Helical strips of thoracic aorta were suspended in oxygenated Krebs-Henseleit solution. Under precontraction with noradrenaline, endothelium-dependent relaxations to acetylcholine were significantly attenuated in the VD and VD + CHOL as compared with the control. Relaxation to calcium ionophore A23187 was also significantly attenuated in the VD + CHOL. However, the relaxing responses to acetylcholine and A23187 in aortas from rats fed a high-cholesterol diet alone remained unaffected. Nitroglycerin caused an equal degree of relaxation in aortas from control and arteriosclerotic rats. There was a significant negative correlation between the relaxing response to acetylcholine and the calcium content in the aorta. These results indicate that in arteriosclerotic rat aortas, the endothelium-dependent relaxation to acetylcholine is impaired in proportion to the degree of calcification, and such impairment is facilitated by cholesterol feeding but can not be attributed to hypercholesterolemia or vascular cholesterol deposition. PMID- 1434129 TI - Protective effects of arbaprostil against indomethacin-induced gastric lesions in rats: significance of maintained gastric blood flow. AB - The purpose of the present study was to investigate the relationship between the effects of 15(R)-15-methylprostaglandin E2 (arbaprostil) on gastric blood flow (GBF) and its protective effects on gastric lesions in rats. The GBF of anesthetized rats was measured by two different methods: Total blood flow into the stomach (total GBF) was determined by means of an ultrasonic pulsed Doppler flow meter; and gastric mucosal blood flow (mucosal GBF) was measured by nonradioactive microspheres. Systemic blood pressure (SBP), heart rate (HR) and gastric vascular resistance (GVR) were recorded simultaneously. Arbaprostil (10 100 micrograms/kg) given i.v. did not affect resting total or mucosal GBF even though it decreased SBP and GVR. Significant improvement of the total and mucosal GBF decreased by indomethacin pretreatment (10 mg/kg, i.v.) was observed by administration of arbaprostil (10-100 micrograms/kg, i.v.) in a dose-dependent manner. Furthermore, i.v.-administration of this agent, in the same dose-range, prevented the formation of gastric lesions induced by indomethacin. The present result suggests that mitigation for the ischemic state of the gastric mucosa may be one of the important mechanisms for the prophylactic and curative effect of arbaprostil on gastric lesions induced by indomethacin. PMID- 1434130 TI - Effects of KW-3635, a novel dibenzoxepin derivative of a selective thromboxane A2 antagonist, on human, guinea pig and rat platelets. AB - We examined the binding of [3H]U-46619, a thromboxane A2 agonist, to human and guinea pig platelets and the binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to human, rat and guinea pig platelets. KW-3635 (sodium (E)-11-[2 (5,6-dimethyl-1- benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxepin-2-c arboxylate monohydrate) concentration-dependently inhibited the [3H]U-46619 binding to human and guinea pig platelets with inhibition constants of 1.2 nM and 2.7 nM, respectively. KW-3635 also potently inhibited the [3H]SQ 29,548 binding to human and guinea pig platelets with inhibition constants of 1.9 nM and 3.2 nM, respectively. In contrast, KW-3635 was less active against thromboxane A2/prostaglandin H2 receptors in rat platelets with an inhibition constant of 97 nM. KW-3635 at 10(-5) M did not antagonize various receptors including prostaglandin E2, prostaglandin I2 and neurotransmitters. In addition, 10(-5) M KW-3635 did not alter the prostaglandin D2-induced cAMP accumulation in EBTr cells. KW-3635 was inactive towards thromboxane synthase, cyclooxygenase and prostaglandin I2 synthase up to 10(-5) M. KW-3635 slightly inhibited 5 lipoxygenase with an IC50 value of 71 microM. These data indicate that KW-3635 is a potent and selective non-prostanoic thromboxane A2 antagonist, and it can recognize the species differences in thromboxane A2/prostaglandin H2 receptors. PMID- 1434131 TI - Basic fibroblast growth factor ameliorates rotational behavior of substantia nigral-transplanted rats with lesions of the dopaminergic nigrostriatal neurons. AB - Basic fibroblast growth factor (bFGF) was injected with dissociated substantia nigral cells into the striatum of rats prepared by unilateral lesion of the nigrostriatal pathway with 6-hydroxydopamine. The transplanted cells with 5 and 50 ng bFGF reduced the apomorphine-induced rotations by 40 and 30%, respectively, while the decrement of rotations was only 15% in the grafted control without bFGF. Immunohistochemical staining with anti-tyrosine hydroxylase antibody showed that bFGF also tended to increase the number of grafted catecholaminergic neurons along the tracts. In the case of 50 ng bFGF treatment but not 0 or 5 ng bFGF treatment, however, severe gliosis was detected along the grafted region by staining of anti-glial fibrillary acidic protein antibody. These immunohistochemical studies suggested that high-dose bFGF induced extensive gliosis, which might affect the survival of the grafted neurons. PMID- 1434132 TI - Regulatory effect of neurotropin on nasal mucosal hypersensitivity in guinea pigs caused by SART (intermittent exposure to cold) stress. AB - We stated that SART-stressed guinea pigs showing nasal mucosal hypersensitivity would serve as an animal model for the in vivo evaluation of antiallergic drugs. In the present study, the mode of action of Neurotropin on nasal allergy compared with those of antiallergic drugs was studied by using SART-stressed guinea pigs. Daily administrations of Neurotropin improved the methacholine-induced hypersecretion and histamine-evoked sneeze response, which are parameters of nasal mucosal hypersensitivity, and increased the density of muscarinic ACh receptors located on the nasal mucosa caused by SART stress. In addition, the inhibitory action on nasal secretion in a passively sensitized model was more intense in SART-stressed guinea pigs than in normal ones. Ketotifen and tranilast were also found to have marked effects on nasal secretion in the passively sensitized SART-stressed model, but only had weak effects on nasal mucosal hypersensitivity. Neurotropin significantly potentiated the action of ketotifen or tranilast. Thus, at least part of the inhibitory effect of Neurotropin on nasal symptoms such as watery secretion and sneezing is thought to have been brought forth through the regulatory action on nasal mucosal hypersensitivity, and its combined use with antiallergic drugs would be a very effective therapeutic regimen for nasal allergy. PMID- 1434133 TI - Caffeine does not effectively ameliorate, but rather may worsen the ethanol intoxication when assessed by discrete avoidance in mice. AB - Ethanol disrupted the discrete lever-press and shuttle avoidances in mice at doses over 1.6 and 2.4 g/kg, p.o., respectively, eliciting a dose-dependent decrease in the % of avoidance with no significant change or slight increase in the response rate. Caffeine increased the response rate of both the avoidances at the doses of 1-30 mg/kg, p.o., but disrupted the avoidance at 100 mg/kg. Caffeine (10 mg/kg) reduced the decreased % of avoidance by ethanol (1.6 and 2.4 g/kg) with a significant increase in the response rate. In contrast, the % of avoidance was significantly lower after the combined administration of ethanol (3.2 g/kg) with caffeine than after ethanol (3.2 g/kg) alone. Unlike ethanol, diazepam (2 mg/kg, s.c.) and pentobarbital (10 mg/kg, s.c.) significantly decreased both the response rate and the % of avoidance. Caffeine (10 mg/kg) ameliorated the decreased response rate and the % of avoidance produced by diazepam and pentobarbital. The present results suggest that caffeine does not effectively ameliorate, but rather may worsen the ethanol intoxication. PMID- 1434134 TI - Anti-stress effect of ginseng on the inhibition of the development of morphine tolerance in stressed mice. AB - We examined how the ginseng extract (GE) acts on the antinociceptive effect induced by footshock (FS)-, psychological (PSY)- and forced swimming (SW)-stress (stress-induced analgesia, SIA), and also on the suppression by FS- and PSY stress of the development of tolerance to morphine in mice. Neither an acute treatment nor 5 daily pretreatments with GE at 100 mg/kg, p.o. affected each SIA. Pretreatment with GE at 100 mg/kg, p.o. for 5 days followed by the treatment in combination with the exposure to stresses for another 5 days caused no appreciable changes in the development of tolerance to FS- and SW-SIA, but suppressed the development of tolerance to PSY-SIA. When mice were pretreated with GE for 5 days and given GE daily prior to morphine at 10 mg/kg/day, with stress exposure for another 5 days, the inhibitory effect of FS-stress on the development of tolerance to morphine was completely eliminated. The present results suggest that GE, by improving the general metabolism in the body, directs toward normalization of the adaptability which is impaired by stress exposure, while not compromising morphine antinociceptive activity or the SIA, another adaptability produced in confrontation to abnormal environmental stimuli. In addition, the differences in the mechanism underlying the FS- and PSY-stress effect which we have previously demonstrated are also reconfirmed. PMID- 1434135 TI - The acyl-CoA synthetase inhibitor triacsin C enhanced eicosanoid release in leukocytes. AB - Triacsin C was previously reported to inhibit long-chain acyl-CoA synthetase and to reduce the production of acyl-CoA in rat neutrophils dose- and time dependently. We found that preincubation with triacsin C inhibited the incorporation of labeled arachidonic acid into rat neutrophils. Furthermore, when triacsin C-treated neutrophils were stimulated with the Ca-ionophore A23187, they released an increased amount of eicosanoids into the culture medium. These results indicate that triacsin C suppressed acylation of arachidonic acid, which resulted in an increase in its metabolites. PMID- 1434136 TI - Nootropic candidates inhibit head-twitches induced by mescaline in mice. AB - The effects of various nootropic candidates on mescaline-induced head-twitches were studied in mice. The number of head-twitches induced by mescaline (100 mg/kg, s.c.) was significantly reduced by idebenone (32 and 100 mg/kg, i.p.), minaprine (0.32-10 mg/kg, p.o.) and nebracetam (100 mg/kg, p.o.). Cholinesterase inhibitors such as tetrahydroaminoacridine (1 and 10 mg/kg, p.o.), NIK-247 (10 and 18 mg/kg, p.o.) and physostigmine (0.32 mg/kg, i.p.) also suppressed the head twitch response to mescaline. These results suggest that the direct or indirect cholinergic-activating effects of these drugs may be involved in inhibiting mescaline-induced head-twitches. PMID- 1434137 TI - Blockade by ginseng extract of the development of reverse tolerance to the ambulation-accelerating effect of methamphetamine in mice. AB - Daily repeated administration of methamphetamine (MAP) developed reverse tolerance to its ambulation-accelerating effect. After pretreatment of mice daily with ginseng extract (GE) for 5 days, concomitant injections of MAP and GE suppressed the development of reverse tolerance to the effect of MAP, although GE itself did not affect the spontaneous motor activity of the naive mice. These results provide evidence that GE may be useful for prevention and therapy of the adverse action of MAP. PMID- 1434138 TI - Relationship between density of muscarinic receptors and nasal hypersecretion in a nasal allergic model. AB - In guinea pigs actively sensitized with ovalbumin, we have observed that nasal hyperreactivity and hypersensitivity to methacholine causes nasal secretion accompanied by an increase in the density of muscarinic acetylcholine receptor (m ACh.R) following the appearance of nasal symptoms induced by the ovalbumin challenge. Therefore in the present investigation, we studied the relationship between the density of m-ACh.R and nasal hypersecretion in actively sensitized guinea pigs. There was no relationship between the quantity of nasal secretion and serum Ig G1 or Ig E levels. On the other hand, the sensitivity to methacholine and nasal secretion induced by methacholine were significantly related to the density of m-ACh.R located on the nasal mucosa. The quantity of nasal secretion induced by allergen was also correlated significantly to the density of m-ACh.R. These results suggest that the nasal hypersecretion observed in the nasal allergic model may be closely associated with an increase in the density of m-ACh.R located on the nasal mucosa. PMID- 1434139 TI - Effects of naloxone and levallorphan on the spinal cord reflex potentials under the spinal ischemic condition in cats. AB - The spinal reflex potentials elicited by electrical stimulation of the tibial nerve were recorded from the lumbo-sacral ventral root in spinal cats. When the thoracic aorta and the bilateral internal mammary arteries were occluded for 10 min, the potentials were completely depressed. Reappearance of these potentials could be observed at about 10 min after removal of the occlusion and they gradually recovered. Intravenous injection of naloxone (1 or 10 mg/kg) or levallorphan (0.1 mg/kg) together with removal of occlusion significantly promoted the recovery of the polysynaptic reflex potential. Morphine (5 mg/kg) showed no particular effect on the recovery of potentials. Furthermore, pretreatment with morphine (5 mg/kg) did not influence the effects of these opioid antagonists. These results suggest that naloxone and levallorphan may preserve or potentiate the interneuronal activities of the lumbo-sacral spinal cord under the ischemic condition and that the effects may not be mediated through morphine-like opioid receptors. PMID- 1434140 TI - Tolerance to the convulsions induced by daily nicotine treatment in rats. AB - Development of tolerance to the nicotine-induced convulsions in rats was examined. Acute intraperitoneal (i.p.) administration of nicotine (2.5, 3.75 and 5 mg/kg) produced convulsions in a dose-dependent manner. Mecamylamine (1 mg/kg, i.p.) antagonized the convulsions, but hexamethonium (5 mg/kg, i.p.) did not modify them. Daily nicotine administration (2.5, 3.75 and 5 mg/kg, i.p.) once a day for 6 days developed tolerance to the convulsions induced by nicotine. After the daily administrations of nicotine for 6 days, the effects of a challenge administration of nicotine (2 mg/kg) on the nicotine-induced convulsions were tested on the 7th-day. Further tolerances were also developed by the 7th-day challenge administration. After the 7th-day test, nicotine levels of the brain and blood 15 min after the challenge injection were measured. With nicotine (5 mg/kg once a day)-treatment, nicotine levels of all the brain regions were increased. In contrast, a similar challenge injection had no effect on blood nicotine level. These results indicate that the development of tolerance to the nicotine-induced convulsions is produced relatively earlier and day by day by daily administrations to rats, which is closely related with the increase in brain nicotine level. PMID- 1434141 TI - Protective effect of benidipine against the development of glomerular sclerosis in experimental nephrotic syndrome. AB - An experimental focal segmental glomerular sclerosis (FSGS) was induced by the combined administration of puromycin aminonucleoside (PAN) and protamine sulfate (PS). Blood collections were made on days 0, 37, 70 and 94. Urine collections were made on days 0, 24, 80 and 94. Vehicle-treated rats showed severe proteinuria and an increase in serum total cholesterol (sTC). Benidipine (1 or 3 mg/kg, p.o.)-treated rats exhibited less proteinuria and lower sTC than the vehicle-treated rats. On days 70 and 94, both blood urea nitrogen (BUN) and serum creatinine (sCR) values in the vehicle-treated rats were significantly higher than those in normal rats (without treatment with PAN and PS). On the other hand, the treatment with benidipine (1 or 3 mg/kg, p.o.) attenuated the increases in BUN and sCR. On day 94, vehicle-treated rats showed a significant decrease in creatinine clearance as compared with normal rats, but benidipine (1 or 3 mg/kg, p.o.)-treated rats did not. The histology was examined on day 94. Vehicle-treated rats demonstrated a significantly greater percentage of glomeruli with segmental areas of glomerulosclerosis/hyalinosis, mesangial cell proliferation, and mesangial foam cell. Benidipine (3 mg/kg, p.o.) ameliorated the development of renal regeneration as estimated by histological examination. These results suggest that the Ca-channel blocker benidipine is a favorable drug for preventing the progression of glomerular sclerosis. PMID- 1434142 TI - Antitumor activity of two novel low immunosuppressive fluoropyrimidines UK-21 and UK-25. AB - We have previously reported that 2',3',5'-tris-O-[N-(2-n-propyl-n pentanoyl)glycyl]-5-fluorouridine (UK-21), a derivative of 5-fluorouridine (5 FUR), and 1-(6-[N-(2-n-propyl-n-pentanoyl)-glycyl]amino-n-hexylcarbamoyl)-5- fluorouracil (UK-25), a derivative of 5-fluorouracil (5-FU), exert their antitumor activity in mice bearing Meth A or EL4 tumor, while their immunosuppressive effects are mild. In the present study, we examined the effects of these compounds on Sarcoma-180 (S-180), P388, L1210, and Lewis lung carcinoma (LLC) in mice by p.o. administration and i.p.-administration. UK-21 given p.o. showed an antitumor effect against S-180, but it showed virtually no antitumor effects against P388, L1210 and LLC. UK-21 given i.p., on the other hand, strongly inhibited the growth of Meth A tumor at a far lower dose than that for oral administration. The bioavailability of UK-21 given p.o. was suspected to be poor. UK-25 given p.o., in contrast, showed the antitumor effect on all of the tumors employed. The bioavailability of UK-25 given p.o. seemed to be comparable to those of other drugs. These results suggest that UK-21 has the potential for development as a parenterally applicable anticancer drug, and UK-25 has the potential as an oral one. PMID- 1434143 TI - Protective effects of antioxidants on paraquat-induced acute renal failure in mice. AB - The protective effects of antioxidants against elevated blood urea nitrogen (BUN) were studied in newly developed acute renal failure in mice induced by paraquat. The administration of paraquat caused marked azotemia accompanied by a decreased glomerular filtration rate. In contrast, elevated BUN was significantly reduced by the preadministration of either dimethylthiourea, deferoxamine or alpha tocopherol. These data suggest that acute renal failure induced by paraquat is mainly related to the hydroxyl radicals produced via the iron-catalyzed Haber Weiss reaction. PMID- 1434144 TI - Characterization of subtype of propylbenzilylcholine mustard (PrBCM)-sensitive and -resistant muscarinic cholinoceptors in guinea pig ileal muscle. AB - The subtype of propylbenzilylcholine mustard (PrBCM)-sensitive and -resistant muscarinic cholinoceptors in guinea pig ileal muscle was examined using four selective muscarinic antagonists, pirenzepine, AF-DX 116, himbacine and 4-DAMP. The pA2 values of the four antagonists against pilocarpine were not different from their values against carbachol after the treatment with PrBCM and was identified with the values for the m3 subtype. These results suggest that the subtype of PrBCM-sensitive and -resistant muscarinic cholinoceptors in guinea pig ileal muscle is the m3 subtype only and not other subtypes. PMID- 1434145 TI - Effects of nitric oxide-related compounds and carperitide on hemodynamics and hematocrit in anesthetized rats. AB - Sodium nitroprusside, nitroglycerin and carperitide (alpha-human ANP) all reduced mean blood pressure, but only carperitide increased the hematocrit in rats with bilateral renal artery- and ureter-ligation. NG-Monomethyl-L-arginine, a selective inhibitor of nitric oxide synthesis, elevated the mean blood pressure but did not change the hematocrit significantly. These findings suggest that ANP has a physiological role in regulating circulatory blood volume distinct from that of NO, although both increase intracellular cyclic GMP in the vasculature. PMID- 1434147 TI - Proceedings of the 25th annual meeting of the Japanese Epilepsy Society and the Japanese Branch of the International League against Epilepsy. Shizuoka, October 4 5, 1991. PMID- 1434148 TI - Does epilepsy cause symptoms other than seizures? PMID- 1434149 TI - Long-term clinicoelectroencephalographic evolution of childhood absence epilepsy. PMID- 1434146 TI - Inhibitory effect of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4 carboxylic acid (SA3443), a novel cyclic disulfide, on the production of TNF-like factor from Propionibacterium acnes-primed rat liver macrophages/Kupffer cells. AB - The effect of (4R)-hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443), a novel cyclic disulfide, on tumor necrosis factor (TNF)-like factor production from Propionibacterium acnes (P. acnes)-primed rat liver macrophages/Kupffer cells was investigated. A remarkable increase in TNF-like activity was detected in the culture supernatants of the liver macrophages/Kupffer cells from P. acnes-treated rats. At concentrations of 1 x 10(-6) to 1 x 10(-4) M, SA3443 significantly inhibited the production/release of TNF-like factor from these P. acnes-primed/activated liver macrophages/Kupffer cells. PMID- 1434150 TI - The seizure prognosis of juvenile myoclonic epilepsy. AB - Thirty-two patients with juvenile myoclonic epilepsy (JME) were studied to evaluate the seizure prognosis. The response to antiepileptic drugs was excellent in 68%, but the patients, who had much more focal discharges on EEG and were sensitive to neuropsychological EEG activations at the beginning of treatment, had an unfavorable outcome. A combination of absence seizure alone resulted in the excellent prognosis for both absence and myoclonic seizures, and a combination of generalized tonic-clonic seizure on awakening related to rare myoclonic seizures. These findings suggest that the outcome of JME would be predicted by the EEG abnormality and the combination of the other types of seizures, which are probably determined by the pathophysiology at the beginning of treatment. PMID- 1434151 TI - Long-term course of childhood epilepsy with intractable grand mal seizures. AB - Twenty-nine children with childhood epilepsy characterized by frequent grand mal (generalized tonic-clonic) seizures in spite of maximal doses of antiepileptic drugs and by an early onset of seizures (before 1 year of age) were followed up for more than 5 years. The children were divided into 3 groups: severe myoclonic epilepsy in infancy (SME), no SME, and intractable childhood epilepsy with generalized tonic-clonic seizures (GTC). In all the 3 groups, the grand mal seizures persisted, whereas the other types of seizures tended to disappear as the patients aged, and the prognosis for mental development was poor. In the majority of cases in all the 3 groups, the waking grand mal seizures altered to sleep grand mal seizures with aging. Two pairs of monozygotic twins with SME suggested that genetic factors play a role in this epileptic syndrome. Intractable childhood epilepsy with GTC is distinguished by the absence of other types of generalized seizures. It cannot be regarded as an epileptic syndrome, but its pathogenesis and treatment require further studies. PMID- 1434152 TI - A long-term follow-up study of first episodes of idiopathic status convulsivus in childhood: in relation to subsequent epilepsy (second report). AB - Fifty-four idiopathic status convulsivus (SC) cases were followed prospectively for a period between 5 and 21 years, the average being 13 years. Three-fourths of the cases had no residuals. There were two patterns of subsequent epilepsy; 1) complex partial seizures (CPS) with or without secondarily generalization (GTS) developed 4.3 +/- 3.5 years after febrile SC, 2) unilateral seizures or CPS +/- GTS developed 1.2 +/- 1.0 years after afebrile SC. The seizure prognosis of these cases was good except for some cases in the former group. There have been two kinds of theories regarding SC and epilepsy until now. One was derived from retrospective studies: SC and/or complex febrile convulsion (FC) were considered the main causes of temporal lobe epilepsy (TLE) producing mesial temporal sclerosis (MTS). Another was derived from prospective studies, in which the relation between FC and TLE was considered weak. Our results revealed that 6 cases (15%) out of 30 febrile SC developed epilepsy, and that five of those six cases were diagnosed as CPS. Three of 5 CPS cases were diagnosed as TLE. Recently the seizure prognosis of operative therapy for TLE--especially the MTS type--has been very favorable. Furthermore, it has become easy to find MTS by Magnetic Resonance Imaging (MRI). So, we emphasize that a precise follow-up study of SC using MRI, EEG, etc., is important in deciding the appropriate therapy for TLE, as well as in the study of the pathogenesis of TLE. PMID- 1434153 TI - The long-term prognosis of patients with temporal lobe epilepsy for more than 20 years. PMID- 1434154 TI - Cooperative prospective study on posttraumatic epilepsy: risk factors and the effect of prophylactic anticonvulsant. PMID- 1434155 TI - Conditions for omitting invasive long-term monitoring before surgical resection in patients with temporal lobe epilepsy. AB - The omission of invasive long-term monitoring before surgical resection in patients with epilepsy should be permitted only for those in whom the epileptogenic focus is presumed to localize unilaterally in the mesial aspect of the temporal lobe. The localization may well be confirmed through noninvasive measures. Retrospective analyses of data obtained from noninvasive investigations (scalp-recorded and sphenoidal EEGs, neuroimages, and electroclinical seizure manifestations) were carried out in 58 patients. The localization of their epileptogenic focus was subsequently confirmed by the implantation of both intracerebral and subdural electrodes; the focus had an amygdalohippocampal origin in 41 patients and a lateral temporal origin in 17 patients. From the comparison of noninvasive findings between these two groups, we propose the following indispensable conditions for omitting an invasive evaluation: 1. Appearance of focal epileptic discharges unilaterally in the sphenoidal lead observed during the simple phase of partial seizures, or unilateral discharges with predominancy in the sphenoidal lead during the early phase of complex partial seizures. 2. Interictal spikes on scalp-recorded EEGs localizing unilaterally in the anterior region of the temporal lobe, and if bilaterally independent, presenting with unilateral predominancy in a ratio of greater than 4:1. 3. Presence of autonomic signs in the initial phase of signal symptoms. 4. Neuroimaging findings in the mesial temporal region: elongated T2 on MRI and hippocampal atrophy, or a tumorous lesion. The lateralization conforms to interictal and ictal paroxysmal EEG findings. There were 8 patients with seizure of amygdalohippocampal origin who satisfied all the indispensable condition, but not a single patient with seizures of lateral temporal origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434156 TI - Surgical treatment for convexity focal epilepsy. AB - Fifty-four cases with intractable convexity focal epilepsy were analyzed with regard to surgical treatment. To acquire satisfactory results, preoperative precise localization of focus and selection of relevant operative methods are indicated. PMID- 1434157 TI - Anterior callosotomy for medically intractable epilepsy. PMID- 1434158 TI - Neuropsychological evaluation before and after surgical treatment of temporal lobe epilepsy. AB - We present the results of pre- and postoperative neuropsychological evaluations of 58 patients with temporal lobe epilepsy who underwent a chronic intracranial EEG monitoring and a subsequent standard anterior temporal lobectomy. Wada's test provided valuable information on the speech dominant side and on the focus localization. Some warning signs as well as verbal automatisms indicated the effect for focus localization and lateralization. The results of interictal neuropsychological tests suggested that each subgroup of TLE performed differently. A postoperative neuropsychological performance has improved in many tests that may be explained by the diminished epileptic bombardment resulting from the resection. PMID- 1434159 TI - Indication of surgery for childhood epilepsy. PMID- 1434160 TI - A morphological study of the cortical pyramidal neuron in the cobalt-induced epileptogenic focus of the cat. PMID- 1434161 TI - Role of surgery in the comprehensive treatment of epilepsies: introduction and summary. PMID- 1434162 TI - A model of status epilepticus induced by intermittent electrical stimulation of the deep prepyriform cortex in rats. PMID- 1434163 TI - The effect of hypoxia on the epileptiform activities induced by magnesium-free medium in rat brain slices. AB - In order to understand the mechanisms underlying the seizure generation, the present study has investigated the effect of hypoxia on the transition between seizure and interictal bursting. Bathing rat brain slices of the hippocampus and entorhinal cortex in magnesium-free medium elicits electrographic seizures. However, they are eventually replaced by the interictal bursts. It has previously been shown that the interictal bursts, arising in the hippocampal area CA3, are propagated to and disrupt the seizure generation in the entorhinal cortex. In this report we demonstrate that hypoxia promotes the seizure reappearance in the entorhinal cortex by suppressing the interictal bursts in CA3. PMID- 1434165 TI - Can we predict carbamazepine responsiveness in partial epilepsy? AB - We studied 153 patients with partial epilepsy who were placed on a carbamazepine monotherapy plan in order to evaluate the clinical factors that may determine drug responsiveness to carbamazepine. The subjects were divided into 3 groups based on their therapeutic outcome--complete seizure control (44%), significant seizure reduction (32%) and unsatisfactory control (24%). Fifteen tentative clinical factors were examined in relation to the therapeutic outcomes. Factors such as seizure type, number of generalized tonic-clonic seizures, age of onset, duration of illness, seizure frequency, previous treatment and EEG finding were relevant to drug responsiveness. However, other variables including mental retardation, etiology, febrile convulsion, positive family history and abnormal neurologic examination showed no significant correlation. Our data suggest that a potential success of carbamazepine treatment should not be underestimated even in patients with complicated clinical features. PMID- 1434164 TI - Temporal lobe CO2 vasoreactivity in patients with complex partial seizures. AB - The topography of CO2 vasoreactivity during hyperventilation in 8 patients with complex partial seizure (CPS) was visualized using the regional cerebral blood flow (rCBF) as measured by H(2)15O-PET (positron emission tomography) and compared with that of 10 normal volunteers. In the normal volunteers, the vascular response to CO2 (VrCO2 = delta CBF%/delta PaCO2) in the temporal lobe was 2.46 +/- 0.56 (%/mmHg). In the patients with CPS, VrCO2 in the temporal lobe of the affected side was 2.08 +/- 0.40 (%/mmHg), while VrCO2 on the contralateral side was 2.30 +/- 0.46 (%/mmHg). There was a significant difference in VrCO2 between the affected side of the temporal lobes and the temporal lobes of the normal volunteers. Furthermore, there was a tendency for VrCO2 to be lower in the affected than in the contralateral side of the temporal lobe in patients with CPS. As CO2 is the main regulator of CBF, this impaired vasoreactivity may reflect the brain dysfunction in the seizure focus and adjacent areas. PMID- 1434166 TI - Sleep grand mal--all-night polygraphic EEG recordings in 20 cases. AB - All-night polygraphic EEG recordings were carried out in 20 epileptic patients who are characterized as follows; 1) clinical attacks took the form of generalized tonic-clonic seizure (GTCS), which occurred only or at least 90% during sleep without other seizure types in awakening, 2) no epileptic discharges were revealed in routine EEG examinations, also including sphenoidal electrode deriving during daytime, 3) recognizable organic brain damage in these patients had been excluded by neurological examinations and CT-scan. Interictal records showed epileptiform abnormalities in 5 of the 20 patients, which were all related with NREM sleep. Four patients exhibited bilateral synchronous paroxysms of 3-3.5 Hz spike-wave short burst and only one patient had temporal-localized discharges. The results of this study demonstrated that although there was a difference compared with other reports, the most characteristic features seen in our patients diagnosed as idiopathic generalized epilepsy (IGE) were as follows: 1) less frequent SGM seizures within a year, 2) SZ onset around teen age, 3) seizures were easily evoked by some precipitating factors and 4) no recognizable organic lesions. As a conclusion, patients with an uncertain or unknown type of epilepsy should always be examined with sleep recordings and all-night sleep recordings if necessary. PMID- 1434167 TI - A preliminary observation on auto-cholinergic synapse dysfunction in patients with different types of epilepsy. AB - Serum anti-acetylcholine receptor antibodies (A AchR Ab) and anti-synaptic premembrane antibodies (A PrM Ab) were measured in 21 patients with absence epilepsy, 21 cases with benign childhood epilepsy with centro-temporal spikes (BCECTs) and 13 cases with atypical epilepsy. Respectively, in five (23.8%), eleven (51.2%) and eight (66.7%) of the above mentioned groups of patients both A AchR Ab and A PrM Ab were found. PMID- 1434168 TI - Status of follow-up among patients with epilepsy in epilepsy clinic. AB - Out of 238 consecutive patients entering our epilepsy clinic from October 1988 till March 1990, the status of follow-up was evaluated in October 1990. One hundred patients (42%) could adhere to the follow-up appointment and 33 patients (14%) visited the clinic irregularly. A total of 105 patients (44%) failed to return for the follow-up at least for 2 months dated backward from October 1990. Seventy-five percent of the patients lost the follow-up within 6 months. The main reasons of the dropout were poor seizure control, seizure free, denial of epilepsy, receiving operation in other hospitals. The appropriate strategies to aid in adherence to medical care among patients with epilepsy should be formulated through the analysis of factors contributing to the dropout, which might be strongly influenced by different medical and sociocultural backgrounds all over the world. PMID- 1434169 TI - Juvenile myoclonic epilepsy in Sri Lanka. PMID- 1434170 TI - Forceps delivery as a risk factor in epilepsy: some further observations. AB - A total of 381 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 the normal group, i.e. 22:10. This was statistically significant (P < 0.05). There was no neurological deficit in any child who had seizures. Both partial and generalized seizures were seen but partial seizures were more frequent. PMID- 1434171 TI - Development of epilepsy in children with perinatal brain injuries: relationship to other neuropsychiatric deficits and EEG features. PMID- 1434172 TI - Clinical study of epileptic type moyamoya disease in children. PMID- 1434173 TI - Specific problems of benign epilepsy of children with centro-temporal EEG foci: prognostic assessment and reconsideration of medical treatment. PMID- 1434174 TI - Long-term effectiveness of antiepileptic drug treatment and seizure recurrence in patients with epilepsy. AB - We studied the rate of seizure recurrence in 334 patients with epilepsy who had received antiepileptic drug (AED) therapy for at least eight years. During the three-year "observation period" (April 1985-March 1988), 163 or 48.8% of the 334 patients were considered to be seizure-free. Seizures were absent in 53 or 81.5% of 65 patients with idiopathic generalized epilepsy, 48 or 40% of 120 with temporal lobe epilepsy, 39 or 39.4% of 99 with partial epilepsy other than those involving the temporal lobe, 2 or 8.3% of 24 with symptomatic generalized epilepsy and 21 or 80.8% of 26 with other epilepsies. Of the 163 patients, 15 or 9.2% suffered seizure(s) during the three-year "follow-up period" (April 1988 March 1991). There was no difference among the different types of epilepsy with respect to seizure recurrence rates. Compared with the 15 patients whose seizures recurred, more of the 148 patients with nonrecurring seizures received AED monotherapy (p < 0.05). However, no significant differences were seen between the two groups for other background factors. PMID- 1434175 TI - Prognosis of temporal lobe epilepsy: report of a multi-institutional study. PMID- 1434176 TI - Lateralizing significance of unilateral upper limb dystonic posturing in temporal lobe seizures. PMID- 1434177 TI - West syndrome associated with chromosome abnormalities: clinicoelectrical study. PMID- 1434178 TI - Polysomnographical study in the patients with West syndrome before treatment. PMID- 1434179 TI - A pathophysiological consideration of 21 cases of reflex epilepsy induced by higher mental activity. PMID- 1434180 TI - Procedural memory in temporal lobe epilepsy. PMID- 1434181 TI - Depressive symptoms in patients with epilepsy. PMID- 1434182 TI - Intravenous administration of anticonvulsants under EEG monitoring in ESES: rapid prediction of the efficacy of oral administration of drugs. PMID- 1434183 TI - The effects of antiepileptic drugs on attentional function in the patient with epilepsy. PMID- 1434184 TI - Comparison of MRI and PET in patients with intractable partial epilepsy of childhood onset. PMID- 1434185 TI - Neuroimaging study of frontal lobe epilepsies. PMID- 1434186 TI - A localized metabolic study of epileptic brains with 31P-chemical shift imaging. PMID- 1434187 TI - Early childhood prolonged convulsions and mesial temporal sclerosis demonstrated by magnetic resonance imaging. PMID- 1434188 TI - Problems of the notification of the name of epilepsy: questionnaire study for parents, teachers and pediatricians. PMID- 1434189 TI - The effect of anticonvulsants on EEG background activity in epileptic children with monopharmacy. PMID- 1434190 TI - Investigation on epileptic spikes by dipole tracing method. PMID- 1434191 TI - Magnetoencephalographic localization of epileptic foci in patients with complex partial seizures using a 37-channel biomagnetometer. PMID- 1434192 TI - Event related potentials evoked by pure tone and linguistic stimulation in epileptic children. PMID- 1434193 TI - Low urea and high ammonia levels in plasma in epileptic patients and their relatives. PMID- 1434194 TI - Periodic hypersomnia: a case with very early onset, age 7. PMID- 1434195 TI - Independent epileptogenic multifoci in a girl with symptomatic partial epilepsy. PMID- 1434196 TI - A case of Lafora disease diagnosed by skin biopsy. PMID- 1434197 TI - Bilateral interhemispheric synchrony and amygdaloid kindling in congenitally acallosal and corpus callosum bisected mice. PMID- 1434198 TI - Changes of the afterdischarge threshold in the primary and secondary sites during kindling of cats: II. A study in neocortical kindling. PMID- 1434199 TI - Increase of pertussis toxin-catalyzed ADP-ribosylation in amygdaloid kindling model of epilepsy. PMID- 1434200 TI - Serotonergic mechanism in hippocampal kindled seizures. PMID- 1434201 TI - Permanent increase in membrane-associated protein kinase C activity in the hippocampal kindled rat. PMID- 1434202 TI - The amygdaloid kindling in developing, adult and aged rats. PMID- 1434203 TI - Alteration in specific [3H]GTP binding in hippocampus of amygdaloid kindled rats. PMID- 1434204 TI - Effect of N-methyl-D-aspartate antagonist on entorhinal responses by amygdala kindling stimulations. PMID- 1434205 TI - Simultaneous recordings of electroencephalograms and multiunit activities in the hippocampus during epileptic seizures of E1 mice. PMID- 1434206 TI - Behavior and EEG changes of unanesthetized cats after kainic acid injection into unilateral caudate nucleus. AB - 1. The microinjection of KA into the unilateral caudate nucleus induces secondarily generalized seizure. 2. The caudate nucleus considered to be one of the important relay structures in the generalization of epilepsy. 3. In this model of caudate nucleus epilepsy, cats did not show spontaneous seizure or choreic movement in the chronic stage. PMID- 1434207 TI - Temporal and spatial differences of the GABAergic abnormalities during development of the E1 mouse. PMID- 1434208 TI - Increased aspartate release from brain slices of epileptic experimental animals and effect of valproate on it. PMID- 1434209 TI - Serial change of cerebral blood flow and intracranial pressure in status epilepticus. PMID- 1434210 TI - Intraoperative measurement of rCBF in epileptic foci using laser Doppler flowmetry in 5 patients with intractable posttraumatic epilepsy. PMID- 1434211 TI - Correlations between local cerebral glucose utilization and electroclinical observations in kainic acid-induced visual cortical seizures in the rat. PMID- 1434212 TI - [The mechanism and specificity of IL-1 inhibitory factor released from human alveolar macrophages]. AB - We have previously reported the presence of interleukin 1 (IL-1) inhibitory factor in the culture supernatants of alveolar macrophages. The activity is decreased in healthy smokers and patients with interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis), compared with healthy non-smokers. In this study, we further examined the mechanism and specificity of IL-1 inhibitory factor. The inhibitory factor exhibited specific inhibition of augmentation by IL-1 of PHA induced murine thymocyte proliferation, whereas there was no inhibition of the augmentation by IL-2, IL-4, IL-6 or TNF. This IL-1 inhibitory factor competitively blocked the binding of IL-1 to the IL-1 receptor on PHA-stimulated murine thymocytes. These results indicate that alveolar macrophages produce a specific IL-1 inhibitory factor which functions as a IL-1 receptor antagonist. PMID- 1434213 TI - [Cytokine gene expression in interstitial lung diseases]. AB - We studied the role of macrophages in the process of pulmonary fibrosis, focusing on gene expressions of cytokines. TGF-alpha is a factor which stimulates fibroblasts or endothelial cells to proliferate, by combining to receptors of EGF competitively with EGF in vitro. Total RNA was extracted from alveolar macrophages recovered by bronchoalveolar lavage from patients with idiopathic pulmonary fibrosis or normal healthy volunteers, and the expression of TGF-alpha mRNA was evaluated by Northern analysis. There was no detectable TGF-alpha mRNA in alveolar macrophages from normal healthy volunteers; however, in patients with idiopathic pulmonary fibrosis, a considerable level of mRNA of TGF-alpha could be detected. Using an experimental rat model of alveolitis induced by bleomycin, the expression of TNF-alpha mRNA in alveolar macrophages recovered by BAL was evaluated by Northern analysis. Alveolar macrophages from bleomycin-treated rats expressed a significant level of TNF-alpha mRNA. Both TGF-alpha and TNF-alpha have proliferative activity on fibroblasts, and may have an important role in the process of fibrosis of the lung. PMID- 1434214 TI - [Alpha 1-antitrypsin genes in patients with alpha 1AT deficiency in Japan: mutational analysis and allelic background]. AB - Deficiency of alpha 1-antitrypsin (alpha 1AT), a plasma serine protease inhibitor, increases the risk of precocious pulmonary emphysema. Patients with alpha 1AT deficiency in Japan are extremely rare and no Z type alpha 1AT deficiency, which is one of the most frequent genetic disorders among Caucasians, are reported in Japan at the level of gene analysis. It is not yet clear why Z type alpha 1AT is rare among Japanese. When Ala213(GCG)-Val213(GTG) mutation in the alpha 1AT gene was examined by restriction endonuclease BstPI, all of 156 Japanese samples were Val213(GTG) in contrast to the finding that 30% of U.S. Caucasians are Ala213(GCG), indicating that alpha 1AT genes among Japanese were diverted from M1(Val213) variant and are different from M1(Ala213) variant, from which Z variant was likely diverted. This may explain why Z type alpha 1AT deficiency is not found among Japanese. A new alpha 1AT deficient variant, Siiyama (Ser53(TCC)-Phe53(TTC)), was found in a 39-year-old male with pulmonary emphysema (Seyama K, et al, J Biol Chem, 266, 12627, 1991). Interestingly, 6 out of 10 families with alpha 1AT deficiency in Japan shared the identical substitution as Siiyama. This indicates that although Caucasian type Z alpha 1AT deficiency is not found, Siiyama variant may be relatively common in Japan and even in other oriental countries because of the historical migration of people. PMID- 1434215 TI - [IgE-mediated allergy and Fc epsilon receptor II]. AB - Two types of IgE receptors, Fc epsilon receptor I (Fc epsilon RI) and Fc epsilon receptor II (Fc epsilon RII), are known to be involved in IgE-mediated allergy. Fc epsilon RI is expressed on mast cells and basophils, and cross-linkage of Fc epsilon RI leads to the release of chemical mediators from these cells. Fc epsilon RI consists of alpha, beta and gamma chains, and cDNAs encoding these chains were recently cloned. Fc epsilon RII is expressed on various cells such as mature mu+delta+ B cells and activated monocytes and eosinophils. The cDNA encoding B cell Fc epsilon RII was cloned by several groups including ours, and Fc epsilon RII was found to be a single chain receptor expressed with its N terminal inside the cells, homologous to C-type animal lectins. Subsequently, we identified two species of Fc epsilon RII, Fc epsilon RIIb, whose structures differ only at the N-terminal cytoplasmic region but share the same C-terminal extracellular region. These two receptors are generated utilizing different transcriptional initiation sites and 5' exons. Fc epsilon RIIa is constitutively expressed only on B cells. While Fc epsilon RIIb is inducible by IL-4 on B cells, monocytes and eosinophils. By employing transformants expressing Fc epsilon RIIa or Fc epsilon RIIb, it was demonstrated that Fc epsilon RIIa is involved in IgE mediated endocytosis, whereas Fc epsilon RIIb functions in IgE-dependent phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434216 TI - [Induction by local injections of IL-2 of antitumor effector cells and secondary production of cytokines in malignant pleural effusion]. AB - The present study was undertaken to examine the effects of intrapleural administration of IL-2 on induction of cytotoxic killer cells and on secondary production of cytokines in malignant pleural effusions. During daily local administration of IL-2, significant in vivo induction of cytotoxic activity was observed after 3-7 days, followed by a decrease in this activity in pleural mononuclear cells (MNC) to almost zero by day 15. IL-4 suppressed induction of IL 2-inducible killer cells from MNC in blood and pleural effusion, but significantly augmented the killer induction from pleural effusion MNC obtained after local 7-day administration of IL-2. Before therapy, malignant pleural effusions contained various levels of IL-6 and M-CSF, but no IL-4 or IFN-gamma. Daily intrapleural instillation of IL-2 resulted in significant augmentation of the levels of IL-4, IL-6, IFN-gamma and M-CSF. Chromatographical fractionation of the pleural effusion showed only one major peak with a MW of 24 kD, which had IL 6 activity. The level of the latent form of TGF-beta also increased during local IL-2 therapy. In contrast, significant levels of TNF (alpha, beta), IL-1 beta or IFN-alpha were not detectable in pleural effusions before or during therapy. These data suggest that IL-2 is an important inducer of secondary production of various cytokines in vivo, responsible for up- or down-regulation of induction of IL-2-inducible killer activity. PMID- 1434217 TI - [Evaluation of physical fitness and exercise performance in patients with chronic pulmonary emphysema]. AB - Physical fitness was studied in patients with chronic pulmonary emphysema using Kraus-Weber methods in addition to pulmonary function and exercise tolerance. In Kraus-Weber tests, explosive strength of abdominal muscles in these patients were within the normal range, but both abdominal and back muscle endurance were significantly diminished compared to age-matched controls. On the other hand, flexibility was not different between the patients and the controls, although large variation was present. Exercise performance as assessed by 6 minutes' walk distance in patients was significantly correlated with FEV1.0, DLco and maximal inspiratory mouth pressure, as well as explosive strength of abdominal muscles and abdominal and back muscle endurance capacity. Treadmill walking training for 20 minutes with a load greater than 80% VO2max, twice a week for 2 months was performed in 11 patients with mild to moderate pulmonary emphysema. Six minutes' walk distance (6MD) was significantly prolonged with improvement of back muscle endurance and flexibility. Another walking training consisting of five repetitions of two minutes' near maximal walking and a two minute interval of rest was performed in 6 patients with severe pulmonary emphysema. 6MD tended to increase with improvement of both back and abdominal muscle endurance. However, pulmonary function tests and VO2max showed no significant changes after both types of training. Improved walked distance after the training was significantly correlated with improved VO2 at AT. Furthermore VO2, VE, HR and lactate production during exercise at the same load were significantly decreased compared to pre-training. Dyspnea sensation measured by modified Borg scale during exercise was improved after the training. It is concluded that a physical training program adapted to the condition of the individual patients could improve exercise performance, and should be prescribed in addition to medication. PMID- 1434218 TI - [Clinical study on respiratory muscle training for chronic respiratory failure]. AB - The purpose of respiratory muscle training for patients with chronic respiratory failure is to improve exercise performance during daily life. Firstly, to confirm the clinical effect on respiratory muscle training, the abdominal pad method for inspiratory muscle training and abdominal pad method with expiratory resistor for both inspiratory and expiratory muscle training were simultaneously performed. Both methods were clinically useful to increase respiratory muscle power and to subjectively decrease dyspnea. Ventilatory pattern analyzed by the Konno-Mead (K M) diagram during exercise also showed their effectiveness. Secondly, the influence of hypoxemia and hypophosphatemia, which are important factors producing respiratory muscle fatigue, was investigated in a patient with respiratory failure. (1) O2 inhalation in patients receiving home oxygen therapy was effective in terms of the endurance time and ventilatory pattern analyzed by the K-M diagram during exercise. (2) A case of hypercapnea due to hypoventilation caused by respiratory muscle fatigue developed reduced PaCO2 following correction of serum phosphate level, suggesting that hypophosphatemia is an important clinical factor producing respiratory muscle fatigue. PMID- 1434219 TI - [Recent technical advances in portable oxygen delivery systems]. AB - According to a Japanese national survey (June 30, 1990), the number of patients receiving home oxygen therapy (HOT) has been greater than 18,000 since March 1985, when HOT was first covered by health insurance. The oxygen concentrator, especially the molecular sieve type, is the most common method of delivery (more than 90%). In April 1988, the portable oxygen cylinder was acknowledged by health insurance, and the liquid oxygen supply system in April 1990. Three types of portable oxygen delivery systems are available; oxygen cyclinder, liquid oxygen system, and oxygen concentrator (membrane type), of which the oxygen cylinder is most commonly used. In our hospital, portable oxygen supply systems were used in 80% of 168 HOT cases in 1990, and the use of 400 L aluminum oxygen cylinders at a flow rate of 1-2 L/min has been most popular. There is an strong desire from patients for lighter portable oxygen supply system of longer duration. In 19 patients with chronic respiratory failure, we evaluated a newly designed demand oxygen delivery system (DODS), which weighs 2.4 kg including the DOD device (TER 20 Teijin), 1.1 L oxygen cylinder made of ultressor, nasal cannula, and carrier. Arterial blood gases at rest (room air) were PaO2 61.9 +/- 6.3 torr, PaCO2 63.8 +/- 9.4 torr and pH 7.40 +/- 0.04. A crossover trial was performed under three conditions; breathing room air with no weight, and pulse oxygen flow and continuous oxygen flow each carrying 2.4 kg of weight. Both 6 minute walking (E1) and walking on a slow speed treadmill (E2) were studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434220 TI - [Psychological approach to chronic respiratory failure]. AB - Patients with chronic respiratory diseases, particularly chronic respiratory failure, are seriously handicapped mentally and physically as compared with those with diseases of other medical fields. This is because their disorders relate to breathing, which is the basic physical function directly associated with sustaining life. The authors have attempted a psychosomatic approach for patients with chronic respiratory disorders. Clinical science in this field of medicine in Japan is far behind that of other advanced nations. In the Comprehensive Emphysema Inventory, it was clearly reported that in many cases, psychological stress is involved in the onset of dyspnea. In SRQ-D or MAS, moreover, decreased motivation for treatment, anxiety regarding prognosis, and conflict were notable in psychosomatic tests. Patients on home oxygen therapy (HOT) appear to have problems in family relations and in the daily-living environment, even though HOT provides both mental and physical benefits. It was also noted that holistic or comprehensive care designed for improvement of not only physical condition, but also psychosocial aspects and quality of life, is essential to achieve good results in the respiratory rehabilitation of patients affected by chronic respiratory failure. PMID- 1434221 TI - [Nutritional assessment and the effect of supplementary oral nutrition in patients with pulmonary emphysema]. AB - Nutritional status and its relation to respiratory function and respiratory muscle strength were assessed in patients with pulmonary emphysema. Energy metabolism was also examined in order to elucidate the mechanism of their malnutrition. BCAA/AAA ratio of plasma amino acid was positively correlated with FEV1.0%. Resting energy expenditure (REE) was negatively correlated with FEV1.0%, and REE/REEpred ratio was also negatively correlated with BCAA/AAA and PImax. These findings suggest that increased mechanical work load, associated with airway obstruction and reduced respiratory muscle efficiency, contribute to the increased energy expenditure and amino acid imbalance. Oral nutritional supplementation using BCAA enriched-elemental diet was found to be effective, as assessed by nutritional parameters, PImax, D.O.E., and QOL index, in malnourished emphysema patients. PMID- 1434223 TI - [Relationship between signal intensity of blood flow in the pulmonary artery obtained by magnetic resonance imaging and results of right cardiac catheterization in patients with pulmonary disease]. AB - Electrocardiogram-gated spin-echo magnetic resonance (MR) images of the chest were obtained in five normal controls and 35 patients with pulmonary disease (11 chronic obstructive pulmonary disease, 6 pulmonary thromboembolism, 5 primary pulmonary hypertension, 4 interstitial pulmonary disease, 4 pulmonary hypertension with disturbance of portal circulation, and 5 other diseases) who underwent right cardiac catheterization. In transverse images at the level of the right main pulmonary artery (rPA) and sagittal images at the level through the midsternal line and the spinal chord, the signal intensity of blood flow in the rPA was quantitatively evaluated, and the correlations with the MR signal intensity of intravascular flow and the parameters of hemodynamics were studied. In diastole MR images of both normal controls and patients mostly showed a significant signal intensity of flowing blood, but in systole some patients demonstrated significant signals and visible flow images. In systolic MR images, the mean values of hemodynamic parameters (mean pulmonary arterial pressure (mPAP), pulmonary arteriolar resistance (PAR), and cardiac index (CI)) were abnormal in patients with significant signal intensity of flow compared with those in patients without sufficient MR signal. The signal intensity was not correlated with mPAP; however, it significantly increased as PAR increased, and it increased as CI decreased both in diastole and in systole. Especially in systole, there was good correlation between the signal intensity in transverse MR images and CI (r = -0.85, P less than 0.01) and between signal intensity in sagittal MR images and PAR (r = 0.90, P less than 0.01). These results suggest that significant flow signal in the rPA in systole has pathophysiological significance, and signal intensity is considered to be significantly affected by changes of PAR and CI. The signal intensity of blood flow in the rPA on MR images can be used as an index of the severity of right heart failure associated with pulmonary disease. MR imaging is a useful modality to evaluate pulmonary circulation disturbance because of its ability to assess blood flow in the pulmonary artery noninvasively without interference from other structures such as bone and normal lung. PMID- 1434222 TI - [Effect of potassium channel openers on hypoxic pulmonary vasoconstriction]. AB - The ATP-sensitive potassium channel (K+ATP) has been suggested as an important mechanism for the reactivity of vascular smooth muscle. We investigated the effects of K+ channel openers (lemakalim, pinacidil) on hypoxic pulmonary vasoconstriction (HPV) and angiotensin II (Ag II) induced vasoconstriction in isolated rat lungs (Sprague-Dawley rats: 300-450 g). Ventilation with hypoxic gas (2% O2, 5% CO2) was performed for 6 min after the injection of Ag II (0.1 microgram). Isolated lungs were perfused under constant flow (0.04 ml/g/min) using 20 ml of blood from donor rat. The perfusion pressure was used as the pulmonary artery pressure. Lemakalim or pinacidil was pre-administered through the reservoir. Pretreatment with pinacidil (10(-4) M) or lemakalim (10(-5) M) inhibited the pressor response to hypoxia, but did not inhibit the response to angiotensin II. Although the effect of lemakalim on HPV was reversed by administration of glibenclamide (10(-5) M) or tolbutamide (10(-3) M), the effect of pinacidil on HPV was not influenced by either drug. These results suggest that 1) K+ channel openers (lemakalim and pinacidil) inhibit the pressor response to hypoxia, and 2) lemakalim seems to act through K+ATP, whereas pinacidil may have other mechanisms of inhibition of vascular smooth muscle contraction. K+ATP may play an important role in the regulation of pulmonary vascular reactivity to hypoxia. PMID- 1434224 TI - [Activity of the respiratory muscles during natural defecation: a study on experimental animals]. AB - Activity of the respiratory muscles during natural defecation was studied in two anesthetized and two decerebrate dogs. In anesthetized dogs, excitation of the abdominal muscles and an increase in gastric pressure were observed during defecation. However, pleural pressure was little influenced by such increase in abdominal pressure, maintaining the same rhythmic changes as observed during spontaneous respiration. The rhythmic changes in pleural pressure were associated with rhythmic activity of the diaphragm. When gastric pressure increased during defecation, the diaphragmatic activity also increased during both the inspiratory and expiratory phases. In a decerebrate dog, airflow and airway pressure changed similarly to during defecation. The diaphragm was continuously active, with superimposed rhythmic augmentation. In a paralyzed and artificially ventilated dog with open-chest, the phrenic nerve similarly developed discharges. We conclude that the non-respiratory activity and rhythmic augmentation of phrenic nerve discharge during defecation is pre-programmed in the command for defecation. The activity of phrenic motoneurons may be further modulated by changes in thoracic and abdominal pressure. These mechanisms may act together to coordinate respiration and defecation. PMID- 1434225 TI - [Production of reactive oxygen species by rat alveolar macrophages. Dissociation between the intracellular and extracellular release of hydrogen peroxide]. AB - In order to clarify the features of reactive oxygen species produced by rat alveolar macrophages (AMs), the concentrations of intracellular and extracellular hydrogen peroxide were measured under various experimental conditions. Intracellular hydrogen peroxide was measured by DCFH method using a flow cytometer, while the extracellularly released fraction was measured by scopoletin method using a spectrophotometer. The concentration of intracellular hydrogen peroxide after stimulation with opsonized zymosan (10 micrograms/ml) was significantly higher than that after stimulation with phorbol myristate acetate (PMA; 100 ng/ml). On the other hand, hydrogen peroxide released extracellularly after stimulation with PMA was significantly greater that that after stimulation with opsonized zymosan. These results indicate that the soluble membrane stimulant and the phagocytic particles have different mechanisms in activating the production of hydrogen peroxide in AMs. That is, hydrogen peroxide induced by PMA was mainly released extracellularly, while that induced by zymosan was mainly released into the intracellular environment. At rest, the concentration of intracellular hydrogen peroxide in rat AMs was high. Potassium cyanate, a known mitochondrial inhibitor, suppressed the intracellular hydrogen peroxide in AMs not only at rest but also after stimulations, indicating that most of the reactive oxygen species released into the intracellular environment in AM are produced by mitochondria. From these results, in order to gain a closer insight into the function of AMs, it is very important to distinguish the oxidative metabolites produced intracellularly which are related to bactericidal function from those of the extracellularly released fraction which give rise to lung damage. PMID- 1434226 TI - [A 14-year-old with pulmonary hamartomatous lymphangiomyomatosis associated with bilateral pneumothoraces]. AB - A 14-year-old girl was admitted because of cough, chest pain and hemosputum. Chest roentgenogram on admission showed a pneumothorax and a cavitary lesion with niveau formation in the right lung and cystic lesions in the bilateral lung fields. After bed rest and intravenous administration of antibiotics for two weeks, the right lung inflated well and the niveau formation disappeared, and the patient was discharged. One week later, she was readmitted with sudden-onset severe dyspnea, caused by bilateral pneumothoraces. Emergency tube thoracostomy and wedge resection of the bullous lesion was performed. Macroscopically, multiple small cystic changes were seen on the surface of the right lung. Histological examination revealed nodular proliferations of smooth muscle cells in the interstitium and vessel walls in the lung, which contained slit-like lymphatic channels. The diagnosis of pulmonary lymphangiomyomatosis was made. In this case, we could not measure receptors for estrogen and progesterone. Recently, hormonal therapy and oophorectomy have been reported as being useful. Tamoxifen (Norvadex) was therefore initiated, and the patient has remained well with slight dyspnea on exertion. There has been no recurrence of pneumothorax. Lymphangiomyomatosis is a rare disease of unknown etiology which occurs exclusively in women, mostly in those of reproductive age. We report a 14-year old female patient with lymphangiomyomatosis associated with repeated pneumothorax, who had been under treatment for epilepsy. We believe this case to be of importance because of the long discussed relation between pulmonary lymphangiomyomatosis and tuberous sclerosis. PMID- 1434227 TI - [A case of bronchocentric granulomatosis associated with uveitis]. AB - A 32-year-old female was admitted to our hospital because of abnormal pulmonary shadows and a decrease in visual acuity. Analysis of peripheral blood revealed eosinophilia, and chest roentgenogram demonstrated multiple infiltrates in the right upper lung field. Pathological examination of transbronchial lung biopsy specimens revealed necrotizing granulomatous lesions in the walls of bronchioles, and a definitive diagnosis of bronchocentric granulomatosis was made. The cause of bronchocentric granulomatosis in this patient was suggested to be an allergic reaction to Aspergillus because of positive response to skin test for Aspergillus. Although it is reported that extrapulmonary involvement is rare in bronchocentric granulomatosis, the present case was associated with uveitis, and to our knowledge is the first reported case. PMID- 1434228 TI - [A case of pulmonary fibrosis in which inhibition of pulmonary vasoconstriction was detected using DSA pulmonary wedge angiography]. AB - A 65-year-old man was admitted to our hospital complaining of productive cough and dyspnea on exertion. X-ray films and CT scan of the chest disclosed diffuse reticular shadows, especially in the bilateral lower lung fields. Blood gas analysis showed severe hypoxemia. Pulmonary function test disclosed severe restrictive pattern. From these findings, the patient was thought to have pulmonary fibrosis. Right heart catheterization showed pulmonary hypertension. To evaluate the pulmonary vascular bed, we performed DSA pulmonary wedge angiography. The pulmonary capillary phase stained homogeneously in normal subjects. However, in the present case, filling of the right pulmonary A9 was incomplete and capillary bed staining was decreased under room air condition. After breathing 5 L/min oxygen for 20 min., the A9 was filled well and capillary bed staining was increased. We consider that this change was induced by inhibition of hypoxic pulmonary vasoconstriction (HPV) by oxygen. DSA pulmonary wedge angiography was useful for visual evaluation of HPV. PMID- 1434229 TI - [A case of early mucoepidermoid carcinoma arising from the left upper bronchus and presenting the flow-volume curve as a manner of extra-thoracic airway obstruction]. AB - A 23-year-old female was admitted with dyspnea, dry cough, and rhonchi. No abnormalities were detected on chest roentgenogram. Fiber-bronchoscopy revealed a polypoid lesion with necrotic material occluding the left main bronchus. The pathological diagnosis of the biopsied material was low grade mucoepidermoid carcinoma. Following tumor reduction by Nd-YAG laser, it was clear that the primary lesion originated from the left upper bronchus. Sleeve lobectomy was performed, and the tumor was proved to be early lung cancer of hilar type with extension limited to the bronchial wall. PMID- 1434230 TI - [An autopsy case of massive pulmonary hemorrhage in systemic lupus erythematosus]. AB - A 60-year-old female was admitted to our hospital because of respiratory failure. She was diagnosed as having systemic lupus erythematosus (SLE) in 1971 and had been treated with low-dose oral corticosteroids for 13 years. She developed cough, fever and anemia several days after oral corticosteroids were tapered. Initially, she had no complications such as congestive heart failure, renal failure or bleeding tendency. Respiratory failure progressed without any response to antibiotic therapy. Chest roentgenogram showed bilateral diffuse infiltrates and air bronchograms. There was no improvement even with steroid pulse therapy, and she died of multiple organ failure. Autopsy revealed massive intra-alveolar hemorrhage and interstitial pneumonitis. Deposition of immunoglobulins in the lung was not seen. To our knowledge, this is the 11th reported case of SLE associated with pulmonary hemorrhage in Japan. PMID- 1434231 TI - [A case of isoniazid (INH)-induced pneumonitis]. AB - A 58-year-old man was referred for the evaluation of a lung nodule on chest X ray. On admission, chest X-ray showed a solitary nodule with cavitation in the left lung field. Histological examination revealed epithelioid cell granulomas and the diagnosis of pulmonary tuberculosis was made. He was treated with INH, ethambutol (EB), and rifampicin (RFP). On the 16th day of treatment, he developed dry cough and high fever. On the 20th day, dyspnea developed and PaO2 was decreased to 38.2 Torr. Chest X-ray showed new widespread infiltrates in both lung fields and bilateral pleural effusions. The size of the cavitary lesion was decreased. Transbronchial biopsy specimen showed slight interstitial thickening, lymphocyte infiltration, and multiple granulomas. Drug lymphocyte stimulation test was positive only with INH (230%). INH-induced pneumonitis was highly suspected. All drugs was discontinued and hydrocortisone 2400 mg daily was started. He soon became afebrile, and dyspnea and dry cough resolved. Chest X-ray film showed resolution of infiltrative shadows. He was subsequently successfully treated with streptomycin, EB, and RFP without any adverse effects. To our knowledge, this is the sixth reported case of INH-induced pneumonitis. PMID- 1434232 TI - [Case of adult primary varicella pneumonia]. AB - We report a case of adult primary varicella pneumonia. A 34-year-old man was admitted to our hospital with fever, dry cough and eruptions. He had no history of chicken pox and his sons had contracted varicella 2 weeks before the onset of his symptoms. Chest X-ray showed diffuse nodular shadows in both lungs. The diagnosis of primary varicella pneumonia was made based on family history, typical eruptions and high titer of antibody against Varicella zoster virus. An electron micrograph indicated this case to be primary varicella pneumonia with fibrosis and edema of interstitial spaces and the presence of virus-like particles in cells. The patient was treated with antibiotics, an antiviral agent and immunoglobulin. The clinical symptoms and diffuse nodular shadows resolved with this treatment. PMID- 1434233 TI - [Two cases of Churg-Strauss syndrome with bilateral wide-spread pulmonary infiltrates]. AB - We report two cases of Churg-Strauss syndrome. The first case was a 25-year-old woman with a one year history of bronchial asthma, who developed fever, skin eruptions, abdominal pain and mononeuritis multiplex. During treatment with prednisolone 40 mg per day, chest X-ray films showed bilateral wide-spread infiltrates. When the dosage of prednisolone was increased to 80 mg per day, these infiltrates disappeared. Skin and lung biopsy specimens demonstrated allergic vasculitis and eosinophilic pneumonia. There was no response to high dose methylprednisolone pulse therapy for persistent severe abdominal pain and mononeuritis multiplex. Pericardial and pleural effusions with eosinophilia recurred eight months later. The second case was a 31-year-old man with a six year history of bronchial asthma, who developed fever, skin eruptions, myalgia and mononeuritis multiplex. One year later, during treatment with prednisolone 15 mg per day, bronchial asthma with eosinophilia relapsed and chest X-ray films showed bilateral patchy infiltrates. Skin biopsy specimens demonstrated eosinophilic infiltrates and necrotizing vasculitis, while lung biopsy specimens demonstrated eosinophilic infiltrates and small granulomas. With additional administration of cyclophosphamide, he has had no evidence of active disease for six years. In both cases, the neurological symptoms persisted despite treatment with high doses of steroids, and during tapering of prednisolone, vasculitis syndrome relapsed. Therefore, long-term careful surveillance is necessary in this disease. PMID- 1434234 TI - [A case of bronchial asthma whose disease activity was associated with changes in serum alkaline phosphatase linked-immunoglobulins levels]. AB - A 67-year-old female was admitted to our hospital with status asthmaticus. Serum alkaline phosphatase (ALP) level was elevated and ALP-linked immunoglobulins (ALP Igs) were detected by ALP isozyme analysis. Treatment with prednisolone resulted in improvement of her asthmatic symptoms and serum ALP level. Thereafter, elevations of serum ALP and ALP-Igs levels were seen whenever she had an asthmatic attack. She had no manifestations of autoimmune diseases. Changes in ALP-Igs levels in association with asthmatic activity suggested that ALP-Igs were related to the pathogenesis of bronchial asthma in this case. PMID- 1434235 TI - [A case of pneumonitis and hepatic injury caused by a herbal drug (sho-saiko to)]. AB - We report a case of pneumonitis and hepatic injury caused by Sho-saiko-to. A 56 year-old man was admitted to our hospital because of hepatic disorder. The levels of serum transaminases returned to normal within two months without specific treatment and he was discharged. Four weeks later, he was readmitted because of severe pneumonitis and mild hepatic disorder. Under the suspicion of drug-induced pneumonitis, all medications were discontinued and high-dose glucocorticoid including "pulse therapy" was given. Consequently, pneumonitis and hepatic function markedly improved. Careful history taking revealed the ingestion of Sho saiko-to before both admissions. Lymphocyte stimulation test against Sho-saiko-to was positive. Challenge test using Sho-saiko-to resulted in decrease of PaO2 and elevation of serum transaminases. Based on these findings, the diagnosis of pneumonitis and hepatic injury induced by Sho-saiko-to was established. PMID- 1434236 TI - [Case report: chronic aggressive pulmonary sarcoidosis with bilateral cavitation]. AB - A 34-year-old male patient was admitted to our hospital because of progressive exertional dyspnea and weight loss (8 kg in one year). Twelve years previously, he had had an episode of uveitis accompanied with bilateral hilar lymphadenopathy. Scalene node biopsy at that time revealed non-caseating epithelioid granulomas. Four years later, a follow-up chest radiograph showed bilateral fine nodular lesions. The bilateral parenchymal lesions gradually increased in density, and eventually, formed a confluent air-space consolidation containing multi-ocular cavities. On physical examination, the patient was emaciated (Ht 165 cm, Wt 40 kg). Nodular cutaneous lesions were present on his face and elbows. Hypoxemia with hypercapnea (PaO2 56 Torr, PaCO2 51 Torr) was noted. Repeated sputum cultures yielded negative results for acid-fast bacilli, fungi, and other pathological organisms. A transbronchial lung biopsy specimen obtained from near the cavitary lesion revealed non-caseating granulomas compatible with sarcoidosis. Skin lesion biopsy showed similar findings. The cavitation, was therefore considered to be due to ischemic necrosis of confluent sarcoid granulomas. Prednisolone (40 mg daily) was given with a prompt improvement of symptoms including dyspnea, as well as the radiographic abnormalities. We conclude that uncomplicated pulmonary sarcoidosis may rarely develop into an aggressive parenchymal disease with cavitation. It is of importance to differentiate such cases from infectious diseases (tuberculosis, mycosis etc.) because of the need for corticosteroid treatment. PMID- 1434237 TI - [A case of bronchoplasty for endobronchial chondroid hamartoma]. AB - A 62-year-old male was admitted to our hospital to investigate his obstructive pneumonia-like symptoms. A chest roentgenography, computed tomography revealed the tumor to be located in the left lower bronchus. Bronchoscopy showed endobronchial tumor at the level of the left lower lobe bronchus. Preoperative pathological confirmation was possible by transbronchial biopsy, pathological diagnosis of the tumor was endobronchial chondroid hamartoma. And then, bronchoplasty was performed. He was discharged from our hospital after operation, showing no evidence. PMID- 1434238 TI - [Active infective endocarditis with idiopathic thrombocytopenic purpura: a case report]. AB - This is a case report of infective endocarditis with idiopathic thrombocytopenic purpura (ITP). Open heart surgery to the patient with ITP has a problem of perioperative hemorrhage. Usually, treatment for ITP is performed before operation, and platelet transfusion is provided for hemorrhage. However, in our patient, we had to perform emergency operation because of progressive heart failure without treatment of ITP. Emergency operation should be performed without treatment of ITP, not to delay operative timing in such a case of progressive heart failure from active infective endocarditis. PMID- 1434239 TI - [Bilocular pericardial cyst diagnosed by magnetic resonance imaging: a case report]. AB - A 47-year-old female who had removal of pericardial cyst is reported. Preoperative examination including echocardiography, computed tomography and magnetic resonance imaging (MRI) demonstrated the cystic nature of the mass attaching to the right pericardial surface. MRI clearly revealed that the cyst was bilocular. MRI brings a more detailed information of pericardial cyst for surgery. PMID- 1434240 TI - [A successful removal of the left ventricular lipoma]. AB - We reported a rare case of left ventricular lipoma, which arose nearby the papillary muscle in the left ventricular wall. It was disclosed by echocardiography and nearly diagnosed by computed tomography and magnetic resonance images. We successfully removed the tumor. It measured 3.8 x 1.5 x 1.3 cm and 3.6 g. Microscopically, it was not encapsulated and consisted of mature adipose tissue. But, it did not invaded the cardiac muscles. In conclusion, the tumor detected lipoma. Postoperative course is uneventful, and the patient has been followed by serial echocardiography. PMID- 1434241 TI - [A case of hydropneumothorax]. AB - A 19-year-old girl was admitted because of fever, cough and suddenly occurred chest pain. One month earlier she had experienced a fever and cough, then she had felt sudden chest pain 2 weeks prior to the admission. A chest X-ray showed left pneumothorax and massive pleural effusion. A diagnosis of hydropneumothorax was made. In spite of the chest tube drainage, reexpansion of the lung was unsatisfactory. Thoracotomy and decortication of the lung resulted in good reexpansion. Histological finding revealed pleuritis due to bacterial peribronchial infection, which resulted in hydropneumothorax, namely an abscess ruptured to the pleural cavity. PMID- 1434242 TI - [Cryosurgery for left atrial myxoma with coronary artery bypass grafting]. AB - This is the first report of cryoblasion of atrial myxoma which was performed in conjunction with coronary artery bypass grafting. A 63-year-old man was admitted for left atrial tumor and ischemic heart disease. Following coronary artery bypass grafting and resection of left atrial myxoma, cryosurgery was carried out for the residual tumor on atrial septum and left atrial posterior wall. Ultrasonic cardiogram after 1 year revealed no signs of recurrence. Cryoablasion was effective in preventing the recurrence of atrial myxoma. PMID- 1434243 TI - [Mitral valve replacement in a patient with hereditary hemorrhagic telangiectasia]. AB - A 46-year-old female with mitral insufficiency complicated by hereditary hemorrhagic telangiectasia (Osler's disease) underwent successfully mitral valve replacement. The patient had a history of repeated large-volume nasal bleeding. Mitral valve replacement using a xenograft was safely performed with various attempts for preventing abnormal postoperative hemorrhage. PMID- 1434244 TI - [Bilateral pneumothorax and rupture of dissecting aortic aneurysm following a mitral valve replacement in Marfan syndrome: a case report]. AB - A 12-year-old girl with Marfan syndrome was referred to our department because of severe mitral regurgitation. The patient was pale and in a pre-shock condition. The echocardiogram revealed a chordae rupture of the posteromedial papillary muscle at the posterior leaflet. A moderate dilatation of the aortic annulus (30 mm) and the ascending aorta (45 mm) without aortic regurgitation was also observed. Emergent mitral valve replacement was performed without replacement of the aortic valve or the ascending aorta. After two months, the patient developed bilateral pneumothorax, which was resistant to continuous suction therapy and finally required surgical treatments. Despite the relatively uneventful recovery, a lethal rupture of dissecting aortic aneurysm into the pericardial cavity, developed four months after the initial operation. We discussed the desired surgical approaches and respiratory problems in patients with connective tissue disorder. PMID- 1434245 TI - [Mitral valve replacement with concomitant coronary bypass for the papillary muscle rupture after acute myocardial infarction in situs inversus]. AB - A 53-year-old man, who was known to have situs inversus totalis all of his life, had acute myocardial infarction complicated by partial rupture of the posterior papillary muscle causing mitral regurgitation and pulmonary edema. The patient underwent mitral valve replacement (Omnicarbon 27 mm) with concomitant aortocoronary saphenous vein bypass, and he is now doing well 9 months following the operation. To our knowledge, this is the first case of the successful mitral valve replacement and concomitant aortocoronary saphenous vein bypass on a patient with situs inversus totalis (mirror-image dextrocardia) in Japan. PMID- 1434246 TI - [Cervical esophago-gastrostomy via the posterior mediastinal route for carcinoma of the thoracic esophagus]. AB - From 1981 to 1990, 297 cases of carcinoma of the thoracic esophagus were resected in our department. Among these cases, 225 cases (84.3%) were reconstructed cervical esophagogastrostomy via the posterior mediastinal route. In this paper, these 225 cases were analysed to evaluate the usefulness of this procedure which was developed by S. Abo in 1975. Operative mortality was 4.4% Anastomotic leakage occurred in 24.4% of the cases, but the majority of the cases were treated successfully without any drainage and 83.3% of the cases could start their diet within one month after operation. The volume of oral intake by the patients after discharge increased satisfactorily (1,500-1,800 kcal/day), but the body weight decreased gradually. So the ambulatory enteral nutritional support was started and proved useful for maintaining their body weight. Alkaline reflux evaluated using 24-hour pH-monitoring system was observed in about half of the cases but the degree of the alkaline shift was not strong. Some complaints (heart burn in 6.3%, regurgitation in 21.9%, feeling of fullness after eating in 40.6%, stenotic sensation in 20.7%) were present but not serious. PMID- 1434247 TI - [Brain dysfunction after operation of aortic arch aneurysm]. AB - Postoperative brain dysfunction was studied for 18 patients who survived more than 30 days after operations of aortic arch aneurysms. The operative procedures were graft replacement in 12 patients, resection with direct or patch closure in 3, and thromboexclusion in 3. Except for thromboexclusion, adjuncts were used: temporary bypass in 1, partial EPC (extracorporeal circulation) in 2, and selective cerebral perfusion during EPC in 12. As for intra-operative monitoring, the temporal artery blood pressures were more than 50 mmHg in all, but the electroencephalogram changed to flat wave just after clamping the aorta in one patient. Postoperative brain dysfunction occurred in 5 patients, including temporary loss of consciousness in 2, lasting loss of consciousness in 1, and paralysis with loss of consciousness in 2. Postoperative brain dysfunction occurred more often in old aged men with atherosclerotic aneurysms. Patients with temporary brain dysfunction had no remarkable change in CT scan, but patients with lasting brain dysfunction had low density areas. It is recommended to prevent this complication as follows: 1) pre-operative evaluation of cerebral vascular disorders, 2) gentle maneuver of atherosclerotic lesions, 3) bilateral cerebral perfusions and intra-operative monitorings, 4) intensive perioperative care of circulation and respiration. PMID- 1434248 TI - [Surgical treatment of coarctation of the aorta]. AB - Repair of coarctation of the aorta was performed in 37 cases (31 patients, 6 patients of reoperation) ranging from 4 days old to 15 years old. Subclavian flap repair were performed in 15, resection and end-to-end anastomosis in 14, patch aortoplasty in 6, and interposition graft in 2. Subclavian flap angioplasty or end-to-end anastomosis is considered the procedure of choice in infants. However, the incidence of reoperation significantly increased in patients younger than age one month at initial subclavian flap repair. Mechanism of recurrent coarctation may be possibly related to retention of abnormal tissue, which is possibly ductal and/or intimal shelf, with the potential for proliferation and luminal narrowing. We suggest that in applicable case end-to-end anastomosis rather than subclavian flap angioplasty may be the surgical technique of choice in infants less than one month of age, and the most common reoperation technique was patch aortoplasty in re-stenosed cases. PMID- 1434249 TI - [Cardiac valve replacement in the elderly]. AB - From January 1980 through December 1990, seventy one consecutive patients over 60 years of age (mean age 64 +/- 4 years) and 231 patients younger than 60 years underwent cardiac valve replacement procedures. In the elderly group, aortic valve replacement was performed in nineteen patients, mitral valve replacement in thirty-three patients both aortic and mitral valve replacement in sixteen patients, and both mitral and tricuspid valve replacement in three patients. Aortocoronary bypass was performed in four and tricuspid annuloplasty in 19 patients simultaneously. Two patients were operated on emergency. As for preoperative status, 63 patients (88.7%) were in New York Heart Association (NYHA) Functional Class III or IV. Mechanical valves were implanted in all aortic position and 16 mitral position. Bioprosthetic valves were placed in 34 mitral position and 3 tricuspid position. Mean follow-up period was 42 +/- 33 months. The early mortality rate was 11% (8 patients) and the actuarial survival rate was 88 +/- 5% at five years and 74 +/- 10% at ten years. Postoperative functional improvement was excellent in 85.7% of the survivors. In the younger age group, 77.9% belonged to NYHA class III or IV preoperatively. The early mortality was 3.0% (7 patients) and the actuarial survival rate was 95 +/- 2% at five years and 86 +/- 2% at ten years. And postoperatively 91.3% were in NYHA class I or II. In conclusion, cardiac valve replacement in the elderly can be performed with an acceptable mortality and excellent functional improvement. PMID- 1434250 TI - [Effects of blood-diltiazem-nitroglycerin-cardioplegia in coronary artery bypass grafting]. AB - Forty-seven patients who underwent coronary artery bypass grafting using blood cardioplegia (BCP) were studied clinically. They were divided into 3 groups based on concentration of diltiazem (DTZ) and nitroglycerin (NTG). Group I (n = 12); DTZ 5 mg plus NTG 5 mg in BCP 1,000 ml, Group II (n = 10); NTG 25 mg in BCP 1,000 ml, Group III (n = 25); DTZ 5 mg plus NTG 25 mg in BCP 1,000 ml. From the standpoint of serum enzyme analysis, there was no significant difference between 3 groups, however, the incidence of perioperative myocardial infarction (PMI) and perioperative coronary spasm (PCS) were significantly higher in Group I than that in other groups. The present data suggests that intramyocardial concentration of NTG in Group II and III were 5 times higher than Group I. Increased dose of NTG in BCP would be benefit for myocardial protection in CABG. PMID- 1434251 TI - [Left heart bypass using a centrifugal pump as an adjunct measure for surgery of thoracic descending aorta]. AB - We have employed left heart bypass (LHB) using a centrifugal pump with heparin coated tubes as an adjunct measure for surgery of thoracic descending aortic aneurysm in 8 cases. During aortic cross-clamping, LHB was controlled to maintain the distal pressure above 50 mmHg. In 7 cases, hemodynamics were stable and no complication occurred in relation with this method. However, acute heart failure due to coronary insufficiency occurred in one patient, and subsequent cardiopulmonary bypass was required to maintain systemic circulation. LHB provides adequate distal perfusion and proximal decompression in most cases, and it has also contributed to diminution of intraoperative bleeding. However, LHB can not maintain distal perfusion when acute heart failure occurs, which indicates that we have to select another adjunct measures, such as femorofemoral bypass to avoid distal hypoperfusion in cases with heart diseases. PMID- 1434252 TI - [A case report on the sliding commissuroplasty for mitral regurgitation due to posterior commissural chordal rupture]. AB - We have performed a mitral valve reconstruction on a 31-year-old man who suffered from infective endocarditis four years ago. Severe mitral regurgitation and posterior commissural chordal rupture were noted. The mitral valve was repaired by Carpentier's sliding commissuroplasty and ring annuloplasty. The postoperative course was uneventful, and mitral regurgitation completely disappeared. It appears that Carpentier's sliding commissuroplasty is a superior new reconstructive technique for mitral regurgitation due to commissural chordal rupture. PMID- 1434253 TI - [Indication of pulmonary embolectomy for acute pulmonary embolism]. AB - During the past 7 years, 15 patients with acute pulmonary embolism (APE) were treated at Kagawa Medical School and 10 patients were survived. Nine patients had an embolus in a right or left pulmonary trunk (group A) and 6 patients were peripheral APE (group B). In group A abnormal findings in a chest x-ray film and an electrocardiogram were observed in many patients, but in group B these findings were slight. In group A a shock was observed in 89% and cardiac arrest in 4 patients, although in group B neither shock nor death were observed. Marked hypoxia with hypocapnia was observed in 8 patients in group A and only in 2 in group B. All patients in group B were recovered by medical therapy. In group A, however, only 3 patients were recovered by medical therapy. Two patients in group A were performed pulmonary embolectomy (PER), but one of them, who had been in nonreversible shock, died. We conclude that the patient who had marked hypoxia (PO2 less than or equal to 50 mmHg) with hypocapnia (PCO2 less than or equal to 35 mmHg) early at an attack should be taken a pulmonary angiography, and when a large embolus is found out in the proximal pulmonary artery, the PER should be performed as soon as possible. PMID- 1434254 TI - [Treatment of postoperative mediastinitis using an omental pedicle flap]. AB - Four patients with postoperative mediastinitis who were treated by omentopexy at the Fukuoka University Hospital between 1989 and 1990. Three of the 4 patients healed successfully, another one died of multiple organ failure 83 days after surgery. All patients were received coronary artery bypass surgery harvesting a left internal thoracic artery for ischemic heart disease. Three patients had diabetes mellitus, one patient had renal failure preoperatively. Recognition of mediastinitis was made by sternal wound purulent discharge and sternal dehiscence. Culture of the discharge fluid yielded methicillin-resistant Staphylococcus aureus in three, and Enterococcus cloacae in one. Irrigation with popidone-iodine or blonopol were ineffective. Thus, the wound was treated with debridement and omentopexy with an omental pedicle flap, respectively. Postoperative course after omentopexy were excellent, had no complications. We conclude that the omentopexy is useful in the treatment of postoperative refractory anterior mediastinitis. PMID- 1434255 TI - [Advantage of internal thoracic artery for coronary arterial bypass surgery in patients over 70 years of age]. AB - Between April 1988 and September 1991, 16 among 23 patients over 70 years of age underwent coronary bypass grafting (CABG) with at least one arterial graft. The age ranged from 70 to 77 years (mean, 72.1 years) and involved coronary lesions were two vessels in two patients and three vessels in 14 patients. Seven patients with unstable angina received emergency CABG. The number of distal anastomosis with arterial graft was mean of 1.3 per patient and left internal thoracic artery (ITA) was used as a pedicled graft in all patients. Sequential grafting with left ITA arterial graft was performed in two and right gastroepiploic artery was concomitantly used in three patients. No atherosclerosis was seen in left ITA, however, poor quality saphenous vein graft (SVG) was in five and atherosclerosis of ascending aorta was in five patients. After operation deep vein thrombosis of leg after harvesting SVG occurred in one patient. The angiogram performed within one month of operation in nine patients showed that the patency rate of arterial graft was 100% and that of SVG was 94.4%. The longest follow-up period was 42 months and New York Heart Association Functional Class improved to Class I or II in all patients. The use of pedicled ITA in elderly patient showed advantage for diseased ascending aorta and it seemed to prevent the postoperative complication due to the use of SVG. PMID- 1434256 TI - [Concomitant cardiac and pulmonary operation in a case of lung tumor with unstable angina]. AB - The patient, a 55-year-old male, suffered from malignant lung tumor with complaints of bloody sputum and anterior chest pain. Angina pectoris was detected during neoadjuvant chemotherapy, because of total obstruction at #7 and 99% stenosis at #12, as disclosed by CAG. As he complained frequently anginal chest pain in the course of time, the concomitant cardiac and pulmonary operation was decided via median sternotomy and fourth intercostal thoracotomy. The operating procedure was as follows: 1) mediastinal lymph nodes dissection before extracorporeal circulation, 2) aorto-coronary bypass (#8, #12), 3) final left lower lobectomy. He was histopathologically diagnosed as a rare case of endobronchial type of leiomyosarcoma. He has achieved a remarkable recovery, without tumor recurrence or angina pectoris for ten months postoperatively, and has been allowed to resume a normal life. PMID- 1434257 TI - [A case of malignant localized visceral pleural mesothelioma]. AB - We experienced malignant localized mesothelioma of which origin was visceral pleura. According to, 1) the preoperative chest X-ray and chest CT which showed extra-pleural sign, 2) the rapid tumor growth, and 3) the result from needle biopsy, we diagnosed malignant localized mesothelioma of which origin was parietal pleura. Surgical treatment was performed, and diagnosed that its origin was visceral pleura. The tumor invaded the lung. It is dangerous to diagnose by means of needle biopsy because of malignant cell implantation. We recommend that firstly the surgical treatment should be carried out for malignant mesothelioma, which needs extended resection for preventing its recurrence. PMID- 1434258 TI - [Computers in urology]. AB - The present state of computer utilization in urology has been described. Nowadays, use of computer is becoming essential in the urological diagnosis and treatment. Recently computers have been so rapidly developed so that it became much smaller and yet offers higher performance. The methods and problems of utilizing computers have been explained by presenting actual examples. An important point that must be recognized in utilizing computers is that the computer is meant to be a part of method in resolving problems and its use itself is not conclusion. In other words, computers are a means of methodology. Computers have been used for frequency analysis in urophonograms, diagnosis in a simultaneous pressure-flow study in lower urinary tract, and for supporting the data entry by photoscanner. Moreover, computers have been used for digital differentiation to materialize higher performance uroflowmeter. Computers have also been applied to litholytic fluid pressure-flow control system for renal stones, and played important role in long hours's intra pelvic pressure monitoring system in support of the large amount of data accumulation and noise reduction. Recently, in the expert system in the pressure-flow study etc., computer plays an essential role which covers most territory of the system. Finally, its future applications have also been speculated. PMID- 1434259 TI - [Complete testicular feminization syndrome associated with thermolabile androgen receptor]. AB - Radioreceptor assay and thermostability test for the androgen receptor in two cases with complete testicular feminization syndrome were performed in regard to the fibroblasts cultured from genital skin on the basis of dispersed whole cell binding assay (Eil et al., 1980). No [3H]dihydrotestosterone binding to the androgen receptor was observed in case 1 (receptor negative), while maximum binding capacity and dissociation constant of androgen receptor for [3H]dihydrotestosterone in case 2 were 21000 sites per cell and 1.67 x 10(-10) M (receptor positive). The specific binding of [3H]dihydrotestosterone to the androgen receptor in case 2 decreased remarkably to 6.6% after high temperature (42 degrees C) incubation in comparison with that at 22 degrees C incubation. The specific binding of [3H]dihydrotestosterone to the androgen receptor in normal controls decreased down to 81.6% at high temperature incubation. Thermostability test was useful to demonstrate qualitative abnormality of androgen receptor in receptor positive testicular feminization syndrome. PMID- 1434260 TI - [Monotherapy with extracorporeal shock wave lithotripsy for renal and ureteral stones]. AB - We performed extracorporeal shock wave lithotripsy (ESWL) as a monotherapy using the Medstone STS lithotripter on 288 patients with renal and ureteral stones between June, 1989 and June, 1991. We compared our results with previous reports on ESWL as used in combination therapy. Our cases consisted of 121 patients with renal stones and 167 patients with ureteral stones. A total of 437 sessions of lithotripsy were performed on 288 patients, for an average of 1.52 sessions of lithotripsy per patient. The percentage of stones measuring less than 4.0 mm in diameter that were fragmented was 94.3% for renal stones and 87.6% for ureteral stones. The stone-free rates 3 months after ESWL were 60.3% and 90.4%, respectively. Our results of the monotherapy with ESWL did not differ from those reported on ESWL as used in combination therapy, in terms of the rate of stone destruction and stone-free rates. We studied the other reports carefully and determined that ESWL monotherapy could have been performed in most those cases. We concluded that ESWL monotherapy is an excellent therapeutic method in the light of fewer complications and side effects compared with those from combination therapy, and the fact that the rate of recurrence for renal and ureteral stones is high makes ESWL monotherapy very useful because the procedure can be repeated. PMID- 1434261 TI - [A study of quantitative and qualitative abnormality of androgen receptor in patients with hypospadias associated with enlarged prostatic utricle]. AB - The prostatic utricle, a rudimentary structure present in the male prostatic urethra, is currently thought to be of mixed origin, with its cranial portion being derived from mullerian duct and caudal segment from wolffian and mullerian ducts and the urogenital sinus. Enlargement of prostatic utricle has often been demonstrated in patients with hypospadias and its incidence increased according to the severity of hypospadias. It has been suggested that insufficient androgenic stimulation of the urogenital sinus and urethral groove during the critical period of sexual differentiation may cause this entity. Since 5 alpha dihydrotestosterone (DHT) is a major androgen for the normal development of urogenital sinus, androgen receptor levels in the patients with hypospadias associated with enlarged prostatic utricle may concern this ontogenesis. Fibroblasts derived from penile skin in these patients were assayed for androgen receptor levels using dispersed whole cell binding assay after Eil (1970). Thermostability of androgen receptor in the same fibroblasts was also evaluated by the remaining androgen receptor activity after incubation at 42 degrees C, and expressed as a ratio (percentage) to the androgen receptor activity in the incubation at 22 degrees C. Preputial skin of endocrinologically normal boys in the same range of age (3 to 8 years) was served as controls. There was a significant difference in averages of maximum binding capacities of [3H]DHT to the androgen receptor between those of controls (n = 4) and patients with grade II utricle (n = 4) (89 +/- 5.7 (SE) x 10(2) sites/cell vs. 37 +/- 7.1 x 10(2) sites/cell).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434262 TI - [Immunological and biochemical characterization of urinary carcinoembryonic antigen and its clinical significance]. AB - The immunobiochemical properties of urinary carcinoembryonic antigen (U-CEA) purified from non-tumor-bearing patients with urinary tract infection were investigated. Moreover, immunohistochemical localization of CEA in the normal urothelium was studied and clinical significance of U-CEA was also analyzed statistically. The purified U-CEA showed a molecular weight of approximately 160,000 by the Western blotting and an antigenicity identical to the purified CEA (Calbiochem Corp.). Amino acids analysis of U-CEA revealed nearly the same values as the purified CEA or the theoretical values of CEA, except for several amino acids susceptible to hydrolysis and sugar chains. Therefore, it was assumed that the U-CEA was a new CEA-related antigen, different from nonspecific cross reacting antigen (NCA) or even CEA itself. Immunohistochemically, CEA was found mainly at the cytoplasmic membrane in normal urothelial cells. The urine samples, collected from patients with various urological disorders, were divided into the inflammation group, showing 5 leukocytes/hpf or more in the urine, and the non inflammation group, showing less than 5 leukocytes/hpf. The groups were subdivided and U-CEA levels were statistically studied; it was found that the U CEA levels strongly reflected the presence of inflammation, rather than the presence of urothelial tumors. Consequently, it was considered that CEA was present in the normal urothelium and that destruction and regeneration of these cells due to tumor or inflammation might release CEA, not NCA, into the urine. PMID- 1434263 TI - [Autologous blood retransfusion in transurethral resection of prostate (TURP)]. AB - Blood collected from the irrigation fluid used during TURP was retransfused in 17 patients. Of the 17 patients, 8 cases were also transfused preoperatively reserved blood. The weight of resected adenoma (g), resection time (minutes), the volume of salvaged blood (ml) of 9 cases who were transfused only salvaged autologous blood were 30.6 g, 63 min. and 355 ml, respectively, and those of 8 patients who were given both salvaged and preoperatively reserved autologous blood were 46.1 g, 78 min. and 703 ml, respectively. No patient was transfused homologous blood. Preoperative urine cultures showed contamination of bacteria in 12 cases (70.6%), and the blood concentrated from irrigated fluid was positive for bacteria in 2 cases (11.8%). Blood count (RBC, Hb, Ht) just after TURP, after blood retransfusion, at the next and the 7th day after the operation were compared to those of just before TURP (Blood Count Ratio). The ratio of the 9 cases who received only salvaged blood were 83.5%, 96.8%, 90.9%, 85.2% each and the ratio of the 8 cases who were transfused both salvaged and preserved blood were 86.9%, 102.6%, 101.4%, 97.5% each. There were no adverse effects due to the autologous blood retransfusion. CONCLUSION: Retransfusion of salvaged autologous blood from the irrigating fluid of TURP was clinically safe and effective. No homologous blood was transfused in TURP when salvaged autologous blood with or without preserved blood was retransfused to the patient. PMID- 1434264 TI - [Effects of magnesium ions on the contraction of the rat detrusor muscle]. AB - Effects of magnesium (Mg) ions on the contraction of the rat detrusor muscle induced by intramural nerve stimulation were investigated in vitro. 1. Frequency response curve demonstrated that contractile responses increased in magnesium free Krebs' solution and decreased in high magnesium solution (MgCl2 5 mM) in comparison with those in normal Krebs' solution. 2. When MgCl2 was added into an organ bath with cumulative way, the magnitude of detrusor contraction decreased dose-dependently. The contractile response was completely abolished by 30 mM MgCl2. 3. Mg ions suppressed the detrusor contraction induced by a high KCl concentration. 4. The effect of Mg ions on the detrusor contraction was enhanced by verapamil but was inhibited by Bay-K8644. 5. Procaine agonized the effect of Mg ions on the detrusor contraction. On the other hand, caffeine did not modify the effect of Mg ions. These results suggest that Mg ions seem to play an inhibitory role on 2 types of Ca-channels existing on the cell membrane and to inhibit release of Ca ions from the intracellular deposit. PMID- 1434265 TI - [Management of multicystic dysplastic kidney detected in perinatal periods]. AB - We analyzed 17 cases of multicystic dysplastic kidney (MCDK) to document the natural history of MCDK and its management. One patient was nephrectomied for respiratory failure associated with MCDK. Follow-up studies of 14 kidneys revealed that 5 kidneys (36%) did not change in size, 7 kidneys (50%) decreased in size. Two kidneys (14%) increased in size during the follow up periods and were nephrectomized. Hypertension and malignancy was not observed in our cases. Evaluations for the contralateral kidney and urinary tract system were performed in 15 patients and 5 (33%) revealed abnormalities--two patients with VUR, 1 with PUJ stenosis, 1 with ureteral stricture and 1 with ectopic ureterocele. In our hospital, the management for MCDK is conservative in most cases. Nephrectomy is indicated when there are complications resulting from the size of MCDK, or when the kidney continues to increase in size after the second year of life. PMID- 1434267 TI - [A study of inhibitory effect of chondroitin polysulfate on stone formation of calcium oxalate]. AB - Chondroitin polysulfate (CPS) have inhibitory activity on stone formation of calcium oxalate. This study compared the inhibitory effect of three CPS (CPS S-I, CPS S-II, CPS S-III) with sodium pentosan polysulfate (SPP) and chondroitin sulfate (CS). Crystal growth inhibition was measured in a seeded crystal growth system with 14C-oxalate, and CPS S-I and CPS S-II were the most active substances inhibiting crystal growth. Since CPS S-II and CPS S-III had remarkable hemorrhagic adverse effect, these two substances were excluded from the following study. The study of administration of the rest of the substances (CPS S-I, SPP, CS) to rats revealed that CPS S-I highly inhibited formation of stone in kidney. About 65 percent of CPS S-I administered subcutaneously was excreted in 24 hours urine. Therefore it may be of value to study clinical usefulness of CPS S-I for treatment of patient with urolithiasis. PMID- 1434266 TI - [Adjuvant chemotherapy for invasive bladder cancer. Multicenter study]. AB - During 2 years and 10 months from November 1985 to September 1988, 50 patients with invasive bladder cancer (pT2-4, pN0-2, M0) were treated with total cystectomy followed by adjuvant combination chemotherapy including cis-platinum. In addition, so-called immunopotentiator (OK-432) and Kanpo (Juzentaihoto: TJ-48) were given to the patients in a random fashion to evaluate whether or not these agents had any significant effect on patients' prognosis. The 3- and 5-year survival rates for 48 evaluable patients were 71% and 67%, respectively. Histologic grade of primary tumors and number of cycles of adjuvant chemotherapy administered had a significant correlation to patients' survival: patients with grade 2 anaplasia had a better 3- and 5-year survival rates than those with grade 3 anaplasia, and patients receiving 3 or more cycles of chemotherapy had a better 3-year survival rate than those with 2 or less cycles. pT and pN categories also affected patients' survival, though not statistically significant. Administration of OK-432 or TJ-48 and pre-operative treatment such as irradiation and intra arterial chemotherapy had no favourable effects on the survival. Side effects of the adjuvant chemotherapy were minimal to moderate and more than 70% of the patients tolerated at least 3 cycles of chemotherapy. It is likely that adjuvant chemotherapy, when given in a post-operative setting, should be repeated at least 3 cycles or more. PMID- 1434268 TI - [Double-blind trial of oral prostaglandin E1 on impotence]. AB - The effect of oral prostaglandin E1 (limaprost) on erectile function was studied in a double-blind placebo controlled trial. Fifty one patients who agreed to participate were examined for their subjective symptoms and nocturnal erection was recorded using an erectometer at the beginning of the study, after an initial 6 week period, and again after a second 6 week period. Patients were randomly assigned to a group which received placebo followed by limaprost or to a group which received limaprost followed by placebo. Ten cases dropped out. In the remaining forty one patients, NPT during the limaprost phase was significantly different from that during the placebo phase. Patients with the history of diabetes mellitus, hypertension, or pelvic surgery showed relatively poor responses to oral prostaglandin E1. Oral prostaglandin E1 achieved 42.9% effectiveness in the psychogenic impotence, and this effectiveness is significantly higher than that of placebo. Oral prostaglandin E1 was suggested as an additional or alternative therapy in the management of psychogenic impotence. Psychogenic impotent who didn't respond to sex therapy and patients with slight organic causes would seem to benefit from oral prostaglandin treatment. PMID- 1434270 TI - [Single-dose captopril test and captopril renal scintigraphy in the evaluation of renovascular hypertension]. AB - The effectiveness of single-dose captopril test (CP-T) and captopril renal scintigraphy with 99mTc-DTPA (CP-RG) in the diagnosis of renovascular hypertension (RVH) was evaluated in 27 patients with (Group I, 16 patients) or without (Group II, 11 patients) renal vascular disease. Group I consisted of RVH in 8 patients (bilateral in 3, unilateral in 5), arteriovenous malformation in 3, renal artery aneurysm in 4, including 2 with essential hypertension, and asymptomatic renal artery stenosis in 1. Group II consisted of 6 hypertensive patients (2 with essential hypertension and 4 with renal hypertension) and 5 normotensive patients. Sensitivity of CP-T and CP-RG in the diagnosis of RVH was 29% (2/7) and 86% (6/7), respectively, indicating the latter was more sensitive than the former. In 3 patients with bilateral RVH, positive response in CP-RG was observed only in the unilateral kidney. Specificity of CP-T and CP-RG was 86% (6/7) and 100% (5/5), respectively in Group I, 100% (8/8) and 83% (5/6), respectively in 16 hypertensive patients. CP-T and CP-RG before and after the treatment of RVH were evaluated in 4 patients. The change of positive response in CP-T and CP-RG into negative after percutaneous transluminal renal angioplasty (PTA) or surgery were found in 3, all followed by a fall in blood pressure, which was not observed in the other patient with positive response after PTA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434269 TI - [Incidence of renal cell carcinoma in Chiba Prefecture, Japan; ten years experience]. AB - Many reports about the increase of renal cell carcinoma patients have been published in Japan recently, however, the real fluctuations in the total number of patients in relation to the change of population have not been reported yet. Most of the patients with renal cell carcinoma in the last 10 years were examined in Chiba prefecture, which has a population of about five million and 25 active urological offices. Histologically confirmed cases were investigated by sending questionnaire letters. The items were as follows; sex, age, address, occupation, family history, past history, symptoms, examination methods that first detected the tumor, operation date, tumor diameter and clinical stage. Twenty two offices returned answers and 560 cases who lived in Chiba were found to have renal cell carcinoma from 1980 to 1989. Yearly incidence rates per 100,000 persons demonstrated a significant increase from 0.32 to 2.07. Small, asymptomatic and low stage cancers have been increasing rapidly, however, the rate of metastatic disease has not shown any decrease. The main cause of rapid increase seems to be attributed to progress in diagnostic methods and increase of early detection, but the possibility of an increase in some carcinogenic factors can not be ruled out. PMID- 1434271 TI - [Endopyeloureterotomy via transpelvic extraureteral approach]. AB - Endopyelotomy has been established as a valuable procedure to relieve the obstruction of ureteropelvic junction or upper ureteral stenosis. However, in a case with a long stenotic segment and in a case with high insertion type of ureteropelvic junction obstruction, we had often poor results by the conventional technique. To resolve these problems, we developed a new technique of endopyeloureterotomy via transpelvic extraureteral approach. We made an auxiliary incision in renal pelvis or dilated ureter involved with stricture to pass a 22 Fr. urethrotome equipped with a cold knife into the retroperitoneal space. Then we incised a stenotic segment by the knife through the urethrotome until the normal caliber of ureteric lumen was found. A 10-16 Fr. stent was left in place in the incised segment for 3 weeks. We treated 38 patients with ureteropelvic junction stenosis or upper ureteral stenosis by this procedure between August 1988 and June 1990. A total of 39 procedures were performed on 39 ureteropelvic junctions or upper ureters. Original disease were congenital anomalies in 23 patients, strictures secondary to urinary calculi in 12 and postoperative strictures in 4. The length of incision was 2 to 6 cm with the average being 3.2 cm. Postoperative follow-up period ranged 4 to 32 months with the average being 19 months. Obstructive changes disappeared or improved in 37 procedures (95%). In two procedures we failed. Thus this new technique of endopyeloureterotomy might be an useful procedure to relieve ureteropelvic junction stenosis or upper ureteral stenosis with a long stenotic segment or high insertion type of ureteropelvic junction stenosis. PMID- 1434272 TI - [Percutaneous transabdominal whole layer core needle biopsy for staging the urinary bladder cancer]. AB - Accurate staging is one of the most important determinants necessary in planning an effective treatment for bladder cancer, but at the present time, staging by the conventional clinical methods are not completely reliable. Accordingly, we have newly developed a percutaneous transabdominal core needle biopsy technique capable of obtaining good cylindrical specimens of the entire layer. In order to obtain the core specimen of the bladder wall, which is a vesico-elastic material, the biopsy needle must penetrate the bladder wall at an extremely high speed. We have developed an original automatic biopsy instrument and modified the head of needle for this purpose. With this method, we could obtain good core specimens for pathological staging in about 90% cases. The correlation between the pathological stagings of core specimens and those of cystectomy specimens were in good agreement. This technique is accurate not only for preoperative pathological staging, but also monitoring histopathologically the responsiveness of multi disciplinary treatment for invasive bladder cancer. This method allows us to determine the optimal therapeutic modality for managing individual patient with invasive bladder cancer. PMID- 1434273 TI - [Prophylaxis of superficial bladder tumor with the intravesical instillation of bacillus Calmette-Guerin or anti-cancer agents. A retrospective study]. AB - It was retrospectively analyzed whether intravesical instillation of bacillus Calmette-Guerin (BCG) or anti-cancer agents had prophylactic effect or not after removal of superficial bladder tumors. The results over a follow-up period ranging from 6 to 40 months showed 23.8 per cent recurrence in group 1 patients treated with BCG (21 patients), 46.7 per cent recurrence in group 2 treated with anti-cancer agents (45 patients) and 52.3 per cent recurrence in the group 3 (127 patients) which were not received any intravesical drugs. Long-term results among the 3 groups calculated with Kaplan-Meier method demonstrated that the instillation of BCG or of anti-cancer agents was more useful for prophylaxis, compared with the actuarial non-recurrence rates of group 3. The instillation of BCG showed good prophylactic effects especially in recurrent, grade 2 and pTa bladder tumors. The instillation of anti-cancer agents showed to provide prolonged protection from recurrence, but the instillation of BCG did not. PMID- 1434274 TI - [Antitumor effect of combined use of purified human natural tumor necrosis factor (N-TNF) and cis-diamminedichoroplatinum (II) (cisplatin) on the implanted bladder carcinoma (MBT-2) in mice]. AB - The antitumor effect of tumor necrosis factor (TNF) in combination with Cis diammine-dichloroplatinum (II) (Cisplatin) upon implanted bladder carcinoma (MBT 2) in mice was analysed together with the toxicity. Mice were implanted into the bladder wall with about 10(4) cells MBT-2 viable cells. TNF was the purified human natural tumor necrosis factor. The antitumor effects were evaluated by the volume of the tumor thus implanted and the drug-toxicity by the body weight of mice and microscopic as well as macroscopic findings of the main organs. As a result, 1) The toxicity of TNF to mice was not enhanced in a dose-dependent fashion when combined with Cisplatin. 2) The antitumor effect by combination of TNF and Cisplatin was significantly increased compared to control group. 3) The effects of TNF was enhanced in a dose-dependent fashion when combined with Cisplatin. 4) The antitumor effects was confirmed by pathological findings. These results suggest that the combined use of n-TNF and Cisplatin is promising as a clinically effective treatment against bladder cancer in human. PMID- 1434276 TI - [Endoscopic operation of congenital anterior urethral valve. Application of flexible renoureteroscope for antegrade urethroscopy]. AB - 4 children with anterior urethral valve were treated by TUR-Valve. Before TUR, valve anatomy could be easily seen by antegrade urethroscopy through cystostomy using a 10.8Fr caliber flexible renoureteroscope and destruction of the valve could be recognized after TUR. Antegrade urethroscopy with a flexible fiberscope was so helpful to TUR-Valve and the findings of voiding cystourethrography and micturition have remarkably improved. This technique is not so difficult to apply and thought to be one of the best methods to recognize valve anatomy and degree of resection. This technique is also applicable to other lower urinary tract lesions in children. PMID- 1434275 TI - [Kock-rectal bladder. Augmented and valved rectum]. AB - Eight patients with total cysto-urethrectomy underwent an augmented and valved rectum (Kock), a type of continent urinary diversion. A satisfactory outcome was obtained in 6 patients. These 6 patients urinated 6 to 8 times a day (1-2 times during the night). The volume each time was 350-450 ml. Urinary incontinence occurred only 1-2 times a month when deeply asleep, and there were no patients whose daily life was restricted. However, there were 3 patients with urinary tract complications. In 2 of them, urinary diversion was required, and unilateral total ureteral obstruction was observed in the remaining patient. The reason for the complications appeared to be that stapling of the intussusception of the sigmoid colon was performed in 5 placements as described in the original method. Following the 4th patient, we were able to prevent any complication in the urinary tract by stapling of the intussusception in 3 places (at 12, 5 and 7 o'clock), and by suturing mucosa to mucosa of the rectum and intussusception in 6 places with polyglycolic acid suture, and further suturing serosa to serosa of the sigmoid colon and rectum in 4 places with silk suture. PMID- 1434277 TI - [A case of inverted Y ureteral duplication with an ectopic ureterocele]. AB - A 29 year-old male with the complaints of two steps urination and sense of residual urine was admitted. At cystoscopy, a ureterocele was found between the normal left ureteric orifice and the bladder neck. Excretory urography demonstrated a radiolucent area in the bladder and a left lower hydroureter. Retrograde pyelography revealed that the left ureter was divided into two branches. Operative exploration demonstrated that the left ureter was an inverted Y ureteral duplication with an ectopic ureterocele; one opened into the ureterocele and the other into the trigone. We resected the ureterocele wall. Four months later, a voiding cystogram did not show vesicoureteric reflux. Now, he has no symptoms and the results of examination are normal. An inverted Y ureteral duplication is the rarest of all anomalies of the ureter. A review of the literature revealed 36 cases reported previously. Clinical analysis was obtained by reviewing 26 of these cases and adding our own (male 10: female 17, average age: 23 years). Complication included 6 cases of ectopic ureteral opening, 6 with blind-ending branch and 5 with ureterocele. The symptoms of this disease depended on the complicating anomalies. The present case was the 5th one of an inverted Y ureteral duplication with a ureterocele in the world literature. PMID- 1434278 TI - [Successful local adoptive immunotherapy for pleuritis carcinomatosa due to renal cell cancer. A case report]. AB - A 54-year-old woman who had undergone radical nephrectomy for renal cell cancer nine months before was admitted to our hospital because of difficulty in breathing. X-ray films of the chest showed massive pleural effusion on the left side and cytological examination of the effusion revealed malignant cells which may have originated from renal cell cancer. Intrapleural instillations of interleukin-2 and of tumor infiltrating lymphocytes isolated from the pleural effusion were performed. After the initiation of the treatment, the pleural effusion decreased and malignant cells disappeared from the pleural fluid. Partial response defined by the criteria provided by the Japan Lung Cancer Society was achieved. No serious side effects were observed. This would be a useful treatment for pleuritis carcinomatosa by renal cell cancer. PMID- 1434279 TI - [Endoscopic surgery and minimally invasive therapy]. PMID- 1434280 TI - [Partial purification of oxalate degrading enzyme produced by human intestinal bacteria]. AB - It is unclear whether the oxalate in foods degrades or not in the intestinal tract. We isolated oxalic acid decarboxylase from anaerobic bacteria present in human feces which was grown in the culture medium containing oxalic acid as the sole carbon source. The enzyme was partially purified by 80% ammonium chloride precipitation, DEAE-cellulose chromatography and molecular sieve chromatography. The amino acid composition was found to be relatively rich in glycine and alanine, but to have low basic, hydrophobic and aromatic amino acid residues compared with average proteins. PMID- 1434281 TI - [Effects of extracorporeal shock waves on renal morphology, renal function and blood pressure in rats--follow-up for one year]. AB - Effects of extracorporeal shock waves on renal tissue, renal function, and blood pressure were studied by applying 500 shock waves to both kidneys in 72 female Wistar rats. Six groups, 12 rats in each, were sacrificed on days, 1, 7 and at months 1, 3, 6 and 12 after the procedure, when serum levels of BUN, creatinine, urine levels of beta 2-microglobulin (beta 2-MG), N-acetyl-beta-D-glucosaminidase (NAG), 28-kDa carbindin-D and creatinine clearance (Ccr) were determined. Findings were then compared with those from the control group. In each group, both kidneys were weighed and histologically evaluated. In the treatment group, systolic blood pressure was measured at post-irradiation months 1, 3, 6, 9, and 12; plasma renin activity was studied 6 and 12 months after irradiation to make evaluation in comparison with the control group. In the treatment group, histologically, coagulative necrosis associated with bleeding around the renal tubules and tubular epithelial cell degeneration were marked on day 1, but the glomerulus was kept in relatively good shape. Inflammatory cellular infiltration and interstitial fibrosis were noted on day 7 and the addition of scar formation 1 month after irradiation. Interstitial fibrosis, inflammatory cellular infiltration, scar formation, and tubular epithelial degeneration remained significant even after 12 months. In the treatment group, kidneys weighed significantly more than in the control group from day 1 through month 3, with edema likely accounting for this. However, weight then significantly declined 12 months after irradiation, owing to suspected scarring atrophy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434282 TI - [Balloon dilation for ureteral stricture with stone fragments after ESWL]. AB - We treated 5 cases of severe hydronephrosis with balloon dilation. Those hydronephrosis were due to the ureteral stricture with small stone fragments after ESWL (Lithostar). In each case, in situ ESWL had been done on a long-lodged ureteric stone with severe hydronephrosis. And even after the disintegration of stone with ESWL, hydronephrosis remained due to ureteral stricture with small stone fragments. Balloon dilation was done through percutaneous nephrostomy tract in 4 cases and via retrograde transurethral routine in 1 case. Balloon dilation catheter (7 fr. 6 mm diameter 4-10 cm length, Bard Co.) was used. There was no need for stone extraction. After dilation, ureteric stents (8.2/7 fr.) were kept in place for 4-8 weeks. Intravenous urogram was taken on 4-8 weeks after removing ureteric stents. In all of the 5 cases, improvement of hydronephrosis was remarkable. And there was no residual stone fragments in 4 cases. It is concluded that balloon dilation for ureteral stricture with stone fragments after ESWL is very useful. For the valid evaluation of balloon dilation, further experience and longer observation are requisite. PMID- 1434283 TI - [Promotive effects of intravesical instillation of dimethylsulfoxide on bladder carcinogenesis in mice]. AB - The effect of intravesical instillation of dimethylsulfoxide (DMSO) on bladder carcinogenesis was examined in mice. Experiment 1: Fifty-five female C3H/He mice were administered 0.05% N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) in their drinking water for 8 weeks. In week 9 they were divided into two groups consisting of 25 mice each. Then, under nembutal anesthesia the first group was given weekly intravesical inatillations of 0.1 ml DMSO (minimum 99.0%) for 10 weeks. The second group received no treatment except anesthesia. All mice were killed 30 weeks after the begining of the experiment and their urinary bladder resected for histological examination. The incidence of bladder carcinoma was 93.7% (15.16) and 27.7% (6/22) in groups 1 and 2, respectively. These incidences differed significantly between the two groups. Experiment 2: One hundred and twenty female C3H/He mice were divided into two groups. The first group was given 0.05% BBN in their drinking water for 5 weeks and then tap water. The second group was not given BBN. In week 6, the first group was divided again into three groups (1, 2 and 3) consisting of 28, 26, and 27 mice, respectively. The second group was divided into groups 4 and 5 consisting of 21 and 18 mice, respectively. Under nembutar anaesthesia groups 1 and 4 received weekly intravesical instillation of 0.05 ml DMSO (minimum 99.0%) from weeks 6 to 13, Group 2 received weekly intravesical instillation of 0.05 ml distilled water from weeks 6 to 13. Groups 3 and 5 received no treatment except anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434284 TI - [Analysis of anchorage independent growth of human prostate cancer cell line LNCap]. AB - LNCap, a human prostate cancer cell line, possess androgen dependent growth characteristics. We studied anchorage independent proliferation of LNCap cells using semi-solid agarose double layer culture. The cells formed colonies in the semi-solid medium supplemented with charcoal filtered steroid free fetal calf serum and maximal colony formation was obtained in the medium with 10% serum. The addition of several steroids (testosterone, dihydrotestosterone, ethinylestradiol) influenced the colony formation. Testosterone at the concentration of 10(-8) M to 10(-10) M stimulated colony formation with optiman of 10(-9) M. When LNCap cells were placed under the basal layer of the semi-solid culture as feeder cells, also stimulated was the colony formation of the LNCap cells cultured in upper layer of semi-solid medium. The addition of EGF, TGF alpha and TGF beta to the medium also stimulated the colony formation. The combined effect of EGF and TGF alpha was shown to be cooperative with testosterone. TGF beta, however, did not show such cooperative effect with testosterone on colony formation. The addition of the anti-body to EGF, TGF alpha or TGF beta to the medium decreased the colony formation of LNCap cells. These results suggest that LNCap cells excrete EGF, TGF alpha, TGF beta and/or similar substances and these factors autocrinely decorate the cell proliferation of LNCap human prostate cancer cells. PMID- 1434285 TI - [Studies on vessel invasion by cancer of the renal pelvis and ureter]. AB - The significance of vessel invasion by cancer of the renal pelvis and ureter was estimated with surgical specimens of 45 patients. The vessel invasion by cancer was observed in 25 out of 45 cases (55.6%). The incidence of vessel invasion increased with the grade of cancer and the extent of the primary tumor. The postoperative metastases by cancer was noted in 22 of the 25 patients with vessel invasion (88%) and in 4 of 20 (20%) patients without vessel invasion. The incidence of metastases in patients with vessel invasion was significantly higher than that without it (p < 0.01). The 5-year survival rate was 13.1% in the patients with vessel invasion and 80.6% in the patients without it (p < 0.005). Postoperative chemotherapy had no effect on the unfavorable outcome of the patients with vessel invasion. Therefore, vessel invasion by cancer may be one of the prognostic factors in renal pelvic and ureteral cancer. The patients with vessel invasion should be treated with more aggressive therapy to improve the poor prognosis. PMID- 1434286 TI - [Chromosomal aberrations in cases of male infertility]. AB - Mitotic chromosomal analysis was done on 130 cases of male infertility, 85 with azoospermia and 45 with oligospermia. Eighteen cases of chromosomal aberrations were found, consisting of eight cases of Klinefelter's syndrome, four with 46, XYq-(including one mosaic case), three translocations, one with 47, XYY, one with 46, XY, 15p+ and one with normal variant. Among these, 46 XYq- is a notable karyotype because it cannot be accurately diagnosed without Q-banding, and because 46, XYq- is important for determining the role of the locus on the long arm of the Y chromosome which is supposed to include spermatogenesis. Eleven cases of 46, XYq- in azoospermic males, including our cases, have been reviewed in the Japanese literature. Statistical analysis of the values of testicular volume and serum hormones in these azoospermia cases, revealed obvious differences between normal and abnormal karyotypes and also between 46, XYq- and Klinefelter's syndrome. PMID- 1434287 TI - [Percutaneous renal cyst puncture and ethanol instillation]. AB - Under ultrasound guidance 79 simple renal cysts in 65 patients were punctured and aspirated with our contrivance, a 5 Fr single J catheter on a 19 gauge needle. Forty-eight renal cysts were successfully punctured, that is, they had no bloody fluid and did not have any leakage of contrast medium. These cysts were instilled with absolute ethanol for 5 minutes. To follow up the patients, consecutive observation was done by sonography or CT every three months. Ethanol-instilled renal cysts were more markedly reduced (reduction rate: 93 +/- 17%) than not instilled cysts (reduction rate: 32 +/- 28%). Thus, ethanol-instillation was useful in the reduction of renal cysts. After the puncture of cysts, hematuria disappeared in most patients. PMID- 1434288 TI - [Effects of luteinizing hormone-releasing hormone agonist on bladder carcinogenesis in male rats]. AB - In previous studies, it has been suggested that the suppression of testicular androgen had inhibits bladder carcinogenesis. In this study we investigated which phase of bladder carcinogenesis is inhibited by the hormonal change of the hypothalamus-pituitary-testicular axis induced by the depot form of the LH-RH agonist. All rats were treated with 0.05% BBN in tap water for 8 weeks and were observed for the following 16 weeks. They were divided into five groups. Group 1 (Control group); The LH-RH agonist was not administered. Group 2 (Initiation group); The LH-RH agonist (depot form) was administered subcutaneously two weeks before and after the initiation of the experiment. Group 3 (Promotion group); The LH-RH agonist (depot form) was subcutaneously administered at intervals of 4 weeks starting 6 weeks after the initiation of the experiment. Group 4 (Full term group); The LH-RH agonist (depot form) was administered subcutaneously at intervals of 4 weeks starting from 2 weeks before the initiation of the experiment. Group 5 (Castration group); Bilateral orchiectomy was performed one week before the beginning of the experiment. From our results, the followings were suggested, (1) more intensive inhibition of bladder carcinogenesis was observed in the group which received the LH-RH agonist (depot form), compared with the Castration group, (2) the bladder carcinogenesis was more intensively inhibited when the LH-RH analogue (depot from) was given in the promotion phase and (3) not only testosterone but also the regulatory system of the hypothalamus pituitary-testicular axis is related to the bladder carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434289 TI - [Effects of bombesin and its antibody on growth of human prostatic carcinoma cell lines]. AB - Bombesin (BMBS), a tetradecapeptide isolated from frog skin, and its antibody were evaluated in vitro and in vivo for their growth modulating effects on human prostatic carcinoma cell lines DU-145 and PC-3. The two cell lines were maintained in DME medium containing 2% FCS and 1 microgram/ml insulin in a humidified atmosphere of 5% CO2/95% air at 37 degrees C. BMBS added at 0.1-10.0 nM caused a striking shift of the concentration-dependent increase in cell growth of DU-145 and PC-3 in the absence of any other exogenously added growth factors. The addition of 1:250 antibody versus BMBS (Ab-BMBS; rabbit antiserum) to the medium during the lag phase of growth resulted in specific inhibition of growth of DU-145 and PC-3 with or without BMBS. Nude mice were transplanted with DU-145 cells in order to evaluate the suppressing qualities of Ab-BMBS on carcinoma cells in vivo. After the inoculation of 10(7) cells/mouse DU-145 into nude mice, 20 microliters/mouse Ab-BMBS was intraperitoneally injected into mice three times weekly for three weeks. In mice administrated with Ab-BMBS, the growth of DU-145 was suppressed markedly. By immunocytochemical study, BMBS immunoreactivities were detected on DU-145 and PC-3 cells. These results suggest that BMBS can function as an autocrine growth factor for human prostatic carcinoma cells. Furthermore, on xenografts in mice, Ab-BMBS inhibits the increase of human prostatic carcinoma. PMID- 1434290 TI - [Neuroanatomical studies on the urine storage facilitatory areas in the cat brain. Part I. Input neuronal structures to the nucleus locus subcoaruleus and the nucleus radicularis pontis oralis]. AB - Input neuronal structures to the nucleus locus subcoeruleus (LSC) and the nucleus reticularis pontis oralis (PoO) were investigated by the horseradish peroxidase (HRP) study in cats. Under halothane anesthesia, a double barreled electrode was inserted into the LSC where electrical stimulation increased bladder capacity and the external urethral sphincter muscle activity, and into the PoO where chemical stimulation with carbachol increased bladder capacity and decreased the external urethral sphincter muscle activity. After identification of these regions, the HRP was ionphoretically injected into the LSC or PoO. By injecting the HRP into the LSC, retrogradely HRP labeled cells were located broadly in the frontal, rectal, orbitalis, rostral cingulate, internal aspect of posterior sigmoidal and anterior sylvian gyli, nucleus corticomedialis of amygdala, lateral area of the hypothalamus, paraventricular hypothalamic nucleus, substantia nigra, periaqueductal gray, reticular formation of the mesencephalon, pons and medulla, cerebellar nuclei and intermediate gray of the spinal cord. By injecting the HRP into the PoO, retrogradely HRP labeled cells were located broadly in the frontal, rectal, orbitalis, internal aspect of the posterior sigmoidal and anterior sylvian gyli, lateral area of the hypothalamus, paraventricular hypothalamic nucleus, periaqueductal gray, reticular formation of the mesencephalon, pons and medulla, cerebellar nuclei and intermediate gray of the spinal cord. These areas where HRP labeled cells were located mostly corresponded to the areas where electrical stimulation evoked either bladder relaxation or contraction in the previous reports. The LSC and the PoO seem to perform important roles in the neuronal mechanism for urine storage, receiving the inputs which facilitate or inhibit micturition from the extended areas between the cerebral cortex and the sacral spinal cord. PMID- 1434291 TI - [Neuroanatomical studies on pontine urine storage facilitatory areas in the cat brain. Part II. Output neuronal structures from the nucleus locus subcoeruleus and the nucleus reticularis pontis oralis]. AB - Output neuronal structures from the nucleus locus subcoeruleus (SLC) and the nucleus reticularis ponts roalis (PoO) were investigated by the wheat germ agglutinin-horseradish peroxidase (WGA-HRP) study in cats. Under halothane anesthesia, a double-barreled electrode was inserted into the LSC, PoO. After identification of these regions, the WGA-HRP was injected ionphoretically into the LSC or PoO. WGA-HRP labeled fibers were observed from the hypothalamus to the sacral spinal cord. Fiber connection was assumed between the WGA-HRP injection sites and areas where WGA-HRP labeled cells were located. There were input and output relationships between the LSC, the PoO and the nucleus locus coeruleus alpha which is the pontine micturition center. By injecting the WGA-HRP into the LSC, two major rostral pathways and four major caudal pathways from the LSC were recognized. Two short caudal pathways projected into the cerebellum and the nucleus raphe magnus. Two long caudal pathways passed through the ipsilateral ventral and contralateral funiculi, and projected into the sacral intermediate gray and the Onuf's nucleus. By injecting the WGA-HRP into the PoO, two major rostral pathways and four major caudal pathways from the PoO were recognized. Three short caudal pathways projected into the cerebellum, contralateral reticular formation of the brain stem and the ipsilateral nucleus reticularis gigantocellularis. One long caudal pathway passed through the ipsilateral ventral funiculus and projected into the sacral intermediate gray and the Onuf's nucleus. From these results, the LSC and the PoO seem to send and receive outputs and inputs each other and to integrate the informations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434292 TI - [Radiotherapy for stage B prostate cancer]. AB - Thirty five cases with stage B prostate cancer underwent radiotherapy to the primary lesion from 1965 to 1989 in our hospital. Twenty two of them were given radiotherapy alone and 13 were treated by radiotherapy combined with hormone therapy. Twenty nine of them were given 113 or 127 TDF (Time, Dose and Fraction) of external radiotherapy using linear accelerator. Three of the other 6 cases underwent external radiotherapy combined with administration of bleomycin and the others received intraoperative irradiation by electron beam. We defined on digital examination a reduction in the primary lesion as improvement and complete flattening as atrophy for evaluation of the treatment. Rates of the improvement were 95% in radiation, alone, and 100% in hormone and radiation combination. Atrophy rates were 62% in the former, and 92% in the latter. Five-year non relapse rates were 85% and 100%, respectively. Four cases relapsed in the radiotherapy alone group, in which two cases given intraoperative irradiation relapsed in the primary lesion and another two given external radiotherapy in the pelvic nodes and required further treatment. One of the 2 relapsed cases with intraoperative irradiation has been alive with cancer and the other died from dissemination. One of the 2 relapsed cases with external radiotherapy has been alive and well and the other died at home without any information of death. One relapsed in the combination group at 130 months but has been alive despite gradually progressive dissemination for 185 months. All relapsed cases were those with atrophy group. No relapse was seen in cases without atrophy of the prostate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434293 TI - [A case report of spermatocytic seminoma--clinical review of 17 cases in Japan]. AB - A male aged 48 visited our department on October 17, complaining of swelling of his left scrotal content from July, 1990. Physical examination showed the testis to be swollen to the size of a chicken egg, and ultrasound examination disclosed the swelling to be solid and nodular. Left high inguinal orchiectomy was performed on October 29. The testis extirpated was 50 x 40 x 45 mm in size and weighted 80 g; the gross appearance of the cut surface of the testis was nodular with grayish-white color. The lesion was proved to be spermatocytic seminoma histopathologically, but no hemorrhage or necrosis was observed. Radiation in the dose of 36 Gy was given over the left hypogastrium and paraaortic region in 36 Gy each. The patient subsequently did will and has been followed up in our outpatient clinic without evidence of recurrence as of 10 postoperative months. This patient was the 19th reported case of spermatocytic seminoma in Japan. However, General Rules for Clinical and Pathological Studies on Testicular Tumors explain that spermatocytic seminoma is usually seen in a pure form, unassociated with other types of germ cell tumors, making our case actually the 17th case of this particular seminoma if spermatocytic seminomas combined with other germ cell tumors are exclude from the statistical analysis. Reports of spermatocytic seminoma thus defined are reviewed in this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434294 TI - [Renal lymphoma. Report of 2 cases and review of the literature]. AB - Two cases of renal lymphoma were reported. Case 1 was a 73-year-old, and case 2 was a 59-year-old female. Their chief complaint was flank pain. The findings obtained by CT and angiography were not compatible with renal cancer. The tentative diagnosis of case 1 was inflammatory disease or soft tissue tumor, and that of case 2 was renal subcapsular tumor. Histological specimen was obtained by open biopsy from case 1, and by nephrectomy from case 2. Immunohistochemical surface marker study revealed both tumors were B cell lymphoma. Chemotherapy (CHOP-Bleo, or PPA) in both cases and additional radiotherapy in case 2 markedly reduced the tumor size. Nevertheless, case 1 died 5 months later from recurrence, and case 2 died 14 months later of gastrointestinal bleeding. At autopsy, the renal subcapsular layer was infiltrated by lymphoma cells in both cases, and lymphadenopathy was not observed. Reviewing 16 cases previously reported as renal lymphoma, the capsular or subcapsular diffuse infiltration to the kidney is considered to be a characteristic feature of renal lymphoma. PMID- 1434295 TI - Latex agglutination test: a simple, rapid and practical method for bovine serum CRP determination. AB - A semi-quantitative latex agglutination test for bovine serum CRP levels has been established by mixing diluted serum (or diluted standard serum) with a 1% latex suspension containing 0.489 micron latex particles coated with affinity-purified antibody at a ratio of 20 micrograms/mg latex. The agglutination was performed on a glass slide in a moist chamber at room temperature with 45 min. incubation. This test is reliable, reproducible and the results correlate with those of the single radial immunodiffusion (SRID) test. The effect of low temperature storage on CRP concentration revealed a 30% degradation of CRP during 2 years storage at 4 degrees C. The possible role of EDTA addition to prevent a decrease in serum CRP concentration by freezing and thawing is also discussed. PMID- 1434296 TI - Detection of equine immunoglobulin-secreting cells by a plaque assay. AB - A protein A-hemolytic plaque assay was applied to detect immunoglobulin (Ig) producing cells in horse peripheral blood, using pokeweed mitogen as a B lymphocyte activator. A maximum number of Ig-secreting cells was obtained when horse peripheral blood lymphocytes were cultured in a medium containing horse serum. The number of Ig-secreting cells in young horses (2 years old) was lower than that in adult horses (6 to 23 years old). In addition, the plaque formation was unchanged from blood samples kept at 4 degrees C for 24 hours, while blood samples kept for 72 hours did not yield plaques. These results indicate that the plaque assay is a reliable and useful method for detecting Ig-secreting cells in the peripheral blood of the horse. PMID- 1434297 TI - Muted victories. PMID- 1434298 TI - Working together for better health care. PMID- 1434299 TI - Physicians' liability for failure to report communicable diseases. PMID- 1434301 TI - Encourage your patients to have mammograms. PMID- 1434300 TI - A core electronic medical library in a rural setting. Part I: The in-house, off line system. PMID- 1434302 TI - Women residents after residency: what does the future hold? PMID- 1434303 TI - Salmonellosis associated with homemade ice cream in Kansas, 1992. PMID- 1434304 TI - How important is a 20-fold risk reduction? PMID- 1434305 TI - Cardiac rehabilitation 1992. AB - The goal of cardiac rehabilitation is to optimize function through attention to the patient's medical needs, risk factors for recurrent events, physical reconditioning, and psycho-social needs. Medical needs include beta-adrenergic blocking agents and aspirin unless contraindicated, angiotensin converting inhibitors for left ventricular dysfunction, and relief of residual ischemia. Smoking, lipid abnormalities, physical inactivity, and hypertension remain important predictors of reinfarction and death and must be controlled. Obesity must be addressed because it exacerbates these problems. Therefore, the principles of behavior change should be applied to help patients control their risk factors and adopt healthy lifestyles. Smoking cessation and appropriate dietary behaviors can be adopted by the patient while in the hospital. Physical reconditioning can also begin with twice-daily exercises. After discharge from hospital and after an initial submaximal exercise evaluation, the patient will benefit from three sessions per week of outpatient cardiac rehabilitation for six to eight weeks. These sessions should last about an hour and raise the patient's heart rate as much as 30 beats per minute. Along with physical reconditioning, the cardiac rehabilitation program provides an opportunity to address risk factor modification, return to work, return to sexual activity, management of depression and anxiety, and the presence of risk factors in the patient's family. The patient should attend reinforcing sessions every three months for the first year and as necessary after that to control risk factors and reinforce the necessity for physical fitness. PMID- 1434306 TI - Quantitative analysis of mesenteric microcirculatory disturbances induced by autonomic nervous irritation. AB - In this study, we have demonstrated that repeated electrical stimuli to the artery of the mesenteric pedicle can produce mesenteric microcirculatory disturbance by autonomic nervous irritation in rats. The parameters to demonstrate microcirculatory damage were observed and quantitatively analyzed using the intravital microscopy after electrical stimulation for 40 minutes. The blood flow of arterioles and venules in the mesentery showed ischemia-reperfusion pattern during the repeated electrical stimulations. The diameter of arterioles did not show significant change, while RBC velocity of arterioles was significantly decreased at 30 min after the irritation. The RBC velocity in venules was decreased from the early period to about 20%. But this values were not significantly dropped during the later observation period, suggesting the formation of short circuit flow by passing the collapsed capillary beds. The number of rolling WBC in the venules was notably increased at the time immediately after irritation, and thereafter the number of rolling WBC number was rather reduced. The number of sticking WBC in venules was time-dependently increased and reached its maximum at 30 min. When permeability of venular wall was determined by the injection of pontamine sky blue, significant increase in permeability was already shown immediately after irritation, suggesting that the integrity of microvascular wall was disturbed in this early period. The permeated area expanded thereafter in parallel with the increase in sticking WBC number. From these observations, it is suggested that endothelial cell damage and following leukocyte-endothelium interaction induced by autonomic nerve irritation appear to be an important factor in microcirculatory disturbances. PMID- 1434307 TI - Role of the sympathetic system in impairment of the cerebrovascular CO2 responsiveness during moderate hypoglycemia. AB - We examined the mechanism of impairment of the cerebrovascular CO2 responsiveness in moderate hypoglycemia. Twelve fasted cats were used. The brain-PO2, brain-PCO2 and brain-pH were measured continuously with electrodes placed on the brain surface. Hypoglycemia was induced with insulin. Intravenous injection of hexamethonium (a sympathetic ganglion blocker, C6; 0.1 mg/kg) was performed at the following stages: Control, hypoglycemia and recovery. Before and after the C6 administration, 5% CO2 in air was inhaled for 3 min at the respective stages. The CO2 responsiveness (cerebrovascular dilatory response to increased PaCO2) at the control stage was not altered after the ganglionic blockade. At the hypoglycemic stage, the increase in BrPO2 by CO2 inhalation was significantly less than that at the control stage. This reduction of delta BrPO2 was significantly improved after the administration of C6. At the recovery stage, the CO2 responsiveness before and after the administration of C6 was not significantly different. An impaired CO2 responsiveness in the hypoglycemic state was improved by sympathetic ganglion blockade with C6 which did not alter the reactivity during normoglycemia. It is suggested that the sympathetic activity plays an important role in impairment of the cerebrovascular CO2 responsiveness during moderate hypoglycemia. PMID- 1434308 TI - Initial predictors of survival in patients with systemic sclerosis (scleroderma). AB - We conducted a retrospective study of 86 patients with systemic sclerosis (SSc) to clarify the initial predictors of survival at the first visit to the hospital. A life-table analysis of survival was performed concerning 137 items from their histories, physical examinations, and laboratory data. The observed cumulative survival rates were 78.0 percent at 5 years and 68.2 percent at 10 years. Ten items were found to be the initial predictors of survival in patients with SSc. Of these 10 items, 9 items showed significant differences within 5 years of the first visit to the hospital. Patients with resting electrocardiographic abnormalities, such as atrial or ventricular arrhythmias, or conduction disturbances, pulmonary fibrosis on the chest x-ray films, or decreased vital capacity had significantly lower survival rates. However, patients with anti centromere antibody had a significantly better survival rate. In addition, males, aged patients over 65 years old, and patients with proteinuria, leucopenia, or hypergammaglobulinemia had significantly lower survival rates. Only patients with proximal scleroderma at the first visit to the hospital had a significantly lower survival rate after 8 years. These results are useful in predicting individual patients at risk of shortened survival and in managing these patients. PMID- 1434309 TI - Cell-mediated cytotoxicity of tumor infiltrating lymphocytes on rat bladder cancer. AB - Tumor-infiltrating lymphocytes (TIL) were tested for cytotoxicity against autologous tumor cells in a study utilizing a chemically induced cancer of the bladder (transitional cell carcinoma), BC-47, in inbred ACI/N rats. From tumors grown after subcutaneous implantation of BC-47 in the rats TIL were separated by density gradient centrifugation and incubated in plastic dishes for separation of non-adherent from adherent cells. The non-adherent cells were further fractionated into T and B cells by the panning method using anti-rat F(ab')2 antibody. The cell fractions were each added to BC-47 in culture to be assessed for antitumor effect by the crystal violet dye exclusion method and 3H-thymidine incorporation inhibition assay. Peripheral blood mononuclear cells (PBMC) were also tested as described above. TIL expressed significantly higher cytotoxicity against BC-47 with the mean % cytotoxicity of 56.6 +/- 5.6% and 87.5 +/- 7.1% at E/T ratios of 10:1 and 20:1, respectively, as compared to PBMC (9.9 +/- 5.0% at E/T 10:1) (P < 0.001). The adherent cells, B and T cell fractions showed respective % cytotoxicity of 92.4 +/- 2.8%, 57.9 +/- 10.6% and 9.9 +/- 7.8% at an E/T ratio of 10:1. TIL pretreated with IFN or rIL-2 for 24 or 48 hours did not exhibit any noticeably enhanced antitumor activity at an E/T ratio of 5:1. Prevention of direct contact of BC-47 cells and TIL by an interposed Millipore membrane (0.45 microns) resulted in an unequivocal reduction of antitumor effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434310 TI - Health profiles of workers exposed to acrylonitrile. AB - The objective of this study was to reveal the health effects of acrylonitrile (AN) in seven Japanese acrylic fiber manufacturing factories. The study subjects were 157 AN-exposed male shift workers who had been exposed to AN for 17 years on the average and 537 control workers whose working conditions were similar to those of the AN-exposed workers. The seven factories were classified into two groups according to their AN exposure levels in 1987, and also into three groups on the basis of 1976 exposure levels. The most highly exposed group of subjects showed a mean AN concentration of 1.13 ppm by personal sampling. Medical examination failed to detect any health effects attributable to long-term exposure to AN, although the existence of some symptoms of acute irritation could not be completely ruled out. The results of this study may provide a "no observed effects level" for human on-the-job exposure with regard to the health effects examined here. PMID- 1434311 TI - Phytosphingosine-containing neutral glycosphingolipids and sulfatides in the human female genital tract: their association in the cervical epithelium and the uterine endometrium and their dissociation in the mucosa of fallopian tube with the menstrual cycle. AB - In human cervical epithelium and uterine endometrium, globo-series neutral glycosphingolipids with N-alpha-hydroxy fatty acyl phytosphingosine (4-D hydroxysphinganine) as the ceramide and sulfatide (I3SO3-GalCer), which were contained in trace amount at the follicular phase, significantly increased in concentration at the luteal phase, comprising about 20% of the individual neutral glycosphingolipids and about 15% of the total acidic glycosphingolipids, respectively. However, in the mucosa of fallopian tube, neutral glycosphingolipids with the same polarity as those in the cervical epithelium and uterine endometrium at the luteal phase and sulfatide remained at a constant and higher level independently of the menstrual cycle. The structures of neutral glycosphingolipids in the fallopian tube, having the same polarity as that of N alpha-hydroxy fatty acyl phytosphingosine-containing molecules appeared in the cervical epithelium and uterine endometrium at the luteal phase, were determined to be N-alpha-hydroxy palmitoyl 4-sphingenine-containing ones by negative-ion FABMS. Also, laminin, but not collagen type IV, was found to be contained in the concentration correlated well with that of sulfatide in the genital tract, when determined by western blotting with monoclonal anti-laminin and anti-collagen type IV antibodies, indicating a possible function of sulfatide as a receptor for laminin in the human female genital tract. PMID- 1434312 TI - Positive and negative symptoms in schizophrenia: application of Jacksonism. AB - Factors influencing prognosis and relapse in schizophrenia were investigated systematically. The results agreed with Jacksonism. Data were collected from 166 patients who suffered relapses and were readmitted to Hospital, into seven categories from Nov 15, 1971 to Dec 31, 1974. The psychiatric symptoms were classified from A to G, positive to negative. The initial symptoms were divided into 4 groups. There was interrelation between the somatic and psychiatric symptoms; in the initial symptoms and the prognosis, courses, and psychiatric symptoms. Based on the author's results, the author suggests that an evolutional and hierarchical interpretation, which Jackson emphasized, in the correlation between brain and mind is applicable in the psychopathology of schizophrenia. PMID- 1434313 TI - Malignant and premalignant lesions of the esophagus. AB - Squamous cell carcinoma is the most common malignant tumor of the esophagus and it is one of the most common fatal cancers worldwide. There is great geographic variation in occurrence of these tumors. Especially high-risk areas have been identified in Northern Iran, Central Asian Republics, Northern China and South Africa. In some of these areas annual mortality rates reach 133/100,000 and over 20% of the population dies of esophageal cancer. The mortality in the US is considerably lower (3 to 8 per 100,000). In common with squamous dysplasias elsewhere eg the cervix, squamous dysplasia of the esophagus also appears to be a precancerous lesion. We have found that squamous dysplasia and early cancer are characterized by a number of distinctive endoscopic changes, namely, mucosal friability, erosions, plaques and nodules. Another finding of interest is the failure on our part to confirm the frequency of esophagitis in high risk areas. Barrett's esophagus is an epithelial metaplasia which replaces esophageal squamous epithelium for variable lengths from the lower esophageal sphincter region cephalad. It is a complication that occurs in approximately 12% of patients with prolonged gastroesophageal reflux. The importance of this disorder is that it is associated with an increased risk of adenocarcinoma of the esophagus. In assessing biopsies from patients with Barrett's esophagus, the main role of the pathologist is to be on the alert for histologic features of dysplasia and adenocarcinoma. Since dysplasia in Barrett's is endoscopically invisible, multiple biopsies are necessary if surveillance is to be successful in detecting dysplastic lesions and early carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434314 TI - [Diagnosis of pulmonary tuberculosis in general hospital "a study of 114 cases"]. AB - We conducted a study on the diagnosis of pulmonary tuberculosis at Chiba Kaihin Municipal Hospital. Examinations were performed to determine the presence of active Mycobacterium tuberculosis in sputum and gastric aspirate. For the sputum smear-negative cases, fiberoptic bronchoscopy was further used as a means for detecting the tuberculosis. The results obtained were as follows: 1. A total of 114 cases in the past six years diagnosed as active pulmonary tuberculosis (including 88 primary treatment cases) were analysed. 2. The 114 cases consisted of 74 males and 40 females, the mean age was 49.3 years old. Categorically, the main age groups were: 60s, 24 cases; 30s, 21 cases; and 40s, 20 cases. 3. Chest X ray findings: Cavitary cases were 28.9% GAKKAI classification of the sizes of the affected areas being Type 1 (mostly limited cases), 58.9% of all total cases, and 68.4% in the cases under the age of 50 years old. The number of cases having infection in a solitary nodule was 19, and the ages of 15 out of the 19 patients were under 50 years old. 4. Sputum or gastric aspirate smear-positive cases totalled 37 (32.5%), and culture-positive cases totalled 77 (67.5%). Sputum or gastric aspirate cultures were positive in 52 out of 56 cases (92.9%) with extended shadows, GAKKAI classification Types 2 and 3, but were positive in 25 out of 58 cases (43.1%) with Type 1. 5. Fiberoptic bronchoscopy was performed on 49 out of the 77 smear-negative cases. 6. Definite diagnosis was obtained in 90 (78.8%) out of total 114 cases. The results of this study suggest that examination for active mycobacterium in sputum and gastric aspirate are very useful for the diagnosis of active pulmonary tuberculosis, especially in extended cases. PMID- 1434315 TI - [A clinical study of tuberculous pleurisy]. AB - Forty-eight cases of tuberculous pleurisy were examined and the following results were obtained. (1) Most of the patients were male, and there was no significant age and underlying diseases. (2) Fever and chest pain were observed mainly in younger patients, and sputum and dyspnea in older patients. (3) All of the cases examined had exudative pleural effusion, and increased ADA activity was frequently observed. (4) Mycobacterium tuberculosis was detected in the sputum of 65%, and also in the pleural effusion of 28% of the patients. The pathological diagnosis of tuberculosis was made by pleural biopsy in 83% of the patients, suggesting that pleural biopsy is very useful in the diagnosis of tuberculosis pleurisy. (5) The prognosis of the patients with tuberculosis pleurisy was good. Steroid therapy was generally ineffective. PMID- 1434316 TI - [Correlation of tuberculin skin reaction with lymphocyte proliferation, interferon-gamma production and tumor necrosis factor-alpha production after in vitro stimulation with PPD and killed Mycobacterium tuberculosis using peripheral blood of healthy donors]. AB - The quantitative relationships among the in vitro lymphocyte proliferation in peripheral blood in 19 healthy donors to purified protein derivative (PPD) and the killed Mycobacterium tuberculosis, interferon-gamma (IFN gamma) and tumor necrosis factor-alpha (TNF alpha) production in these culture supernatants, and the in vivo skin reaction to PPD which were simultaneously measured were studied. Statistical analysis was performed with t-test and multiple regression analysis: The results obtained were as follows; 1) The magnitude of the in vitro lymphocyte proliferation by PPD and the killed M. tuberculosis failed to correlate with the erythema and the induration of the in vivo skin reaction to PPD. 2) The erythema of skin test correlates with TNF alpha production in the culture supernatants that the lymphocytes in peripheral blood were cocultured with these antigens for 7 days. (R = 0.566062, 0.01 less than p less than 0.02) 3) There is a correlation between the erythema and the induration of skin test. (R = 0.526662, 0.02 less than p less than 0.05). 4) Though the magnitude of the lymphocyte proliferation to PPD correlates IFN gamma production in the culture supernatants (R = 0.525915, 0.02 less than p less than 0.05), these response to the killed M. tuberculosis correlates both IFN gamma production (R = 0.55049, 0.01 less than p less than 0.02) and TNF alpha production (R = 0.51283, 0.02 less than p less than 0.05) in the culture supernatants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434317 TI - [A recovered case of serious lung tuberculosis on wanderer]. AB - This report is a case study of a vagrant whose state of tuberculosis showed noteworthy improvement due to clinical treatment. A 54-year-old male, vagrant, was admitted to the hospital in a state of preshock because of a serious stage of lung tuberculosis. The clinical course was severe, but after three months of intensive care the patient recovered. It was noted that the echocardiogram taken after recovery revealed improvement when compared with the one taken upon admission, which showed remarkable right ventricular overload. Furthermore, anti tuberculosis agents proved to be very effective in this case. The patients respiratory functions improved more markedly than had been expected. The reason for reporting this case study is to bring attention to the improvements in the patient's clinical course and echocardiographic findings. These suggest that tuberculosis in vagrants may differ from the usual stage of tuberculosis diagnosed in elderly persons in terms of response to anti-tuberculosis agents and potential recovery. PMID- 1434318 TI - [Rapid diagnosis of mycobacteria, especially Mycobacterium tuberculosis and Mycobacterium avium complex, using MB Check system]. AB - Fourty-five sputum specimens were subjected to isolation for mycobacteria either MB Check system (MB method; F. Hoffmann-La Roche Ltd., Basel, Switzerland) or 3% Ogawa egg medium (Ogawa method). Test sputum was treated with 4 volumes of 4% NaOH for 1-2 min and 0.1 ml of the resulting mixture was inoculated onto 3% Ogawa egg medium. The remaining portion of the mixture was neutralized with IN HCl, diluted with 1/15 M phosphate buffer (PB; pH 6.8), and subsequently centrifuged at 3,000 rpm for 20 min. The sediment was suspended in 1.5 ml of PB and 0.5 ml each was inoculated into MB Check M bottle (20 ml) supplemented with M supplement (1 ml). In MB method, bacterial growth was measured on Middlebrook 7H11 agar medium and Middlebrook 7H11 agar medium containing NAP (p-nitro-alpha-acetylamino beta-hydroxy-propiophenone). Among 45 sputum specimens, the number of positive specimens for mycobacterial growth in the above two cultivation methods and time required for growth were as follows: 3% Ogawa egg medium; 12 specimens (26.7%) gave positive growth, including 7 of M. tuberculosis complex strains on 14-35 days (average 22 days) and 5 of M. avium complex strains on 14-21 days (average 18 days); MB method; 15 of specimens (33.3%) gave positive growth, including 8 of M. tuberculosis complex strains on 7-21 days (average 15 days), 6 of M. avium complex strains on 7-14 days (average 11 days) and 1 of M. scrofulaceum strain on 28 days. There was no specimen which was positive for mycobacterial growth on 3% Ogawa egg medium but negative on MB medium. PMID- 1434319 TI - [Phenotypic analysis in peripheral blood lymphocytes of patients with pulmonary tuberculosis]. AB - In order to clarify the immunological aspects of tuberculosis, phenotype of peripheral blood lymphocytes was analyzed in 96 patients with pulmonary tuberculosis and 43 normal controls. In tuberculosis, CD8 positive T cells were significantly decreased in comparison with normal controls and regarding expression of CD3, CD4, CD19, CD16 and gamma delta T cell receptor (TCR), there was no significant difference between tuberculosis and normal controls, though in tuberculosis CD4 positive T cells tended to be high as compared to normal controls. With respect to previous therapeutic condition, the group with previous chemotherapy had significantly high CD4 positive cells, low CD8 positive cells and low gamma delta TCR positive cells as compared to the group without previous chemotherapy. Between groups divided by Type or Expansion of pulmonary tuberculosis without previous chemotherapy, there was no significant difference regarding any surface markers. Regarding pulmonary tuberculosis with previous chemotherapy, the group of Type II had significantly high CD4 positive cells and low CD8 positive cells as compared to Type III, and in the group of Expansion 3, CD19 positive cells were significantly high as compared to Expansion 2. Characteristic of phenotype in peripheral blood lymphocytes of patients with pulmonary tuberculosis is predominant CD4 positive cells in a corresponding decrease in the proportion of CD8 positive cells and is no elevation of gamma delta TCR positive T cells. PMID- 1434320 TI - [Clinical characteristics of the patients with primary infection of Mycobacterium avium complex]. AB - Clinical characteristics are analyzed in patients with primary infection of Mycobacterium avium complex (MAC). The definition of primary infection of MAC are determined as follows; 1) MAC is found several times since the beginning of the disease, 2) clinical symptoms or abnormal shadow corresponding to MAC infection on chest roentgenogram, 3) no old tuberculous lesions nor other abnormal shadows like bronchiectasis, 4) no abnormal serological results suggesting other bacterial or viral infections. According to this definition, 17 out of 84 MAC patients are diagnosed as primary MAC infection, and clinical features are analyzed in these 17 patients. Average age of patients is 61.1 +/- 12.9 year old. This age is significantly higher than that of inpatients with pulmonary tuberculosis in our hospital, and lower than that of all MAC patients including secondary infection. Five (29.4%) are male and 12 (70.6%) are female, the ratio of male to female is 1 to 2.4. This value is significantly different with that of inpatients with pulmonary tuberculosis in our hospital who show about 3 to 1. Most of the patients complained of cough with sputum, especially of hemosputum. Eleven out of 17 patients (64.7%) complained repeated hemosputum. The frequency of hemosputum is very high compared with that of the patients with pulmonary tuberculosis (about 20%). No compromised condition was present except for a patient with Behcet's disease who are taking steroid hormone. Roentgenographic features of primary infection are those of scattered small nodular lesions in the peripheral part of the lung, thin wall cavity formation, no contraction of the diseased lung nor dislocation of the trachea.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434321 TI - [On the problems of the antituberculous drug resistance]. AB - In this part, we will discuss exclusively about the technique of measurement. It is desirable especially for the proportion method that two inoculations with the same doses give the same number of colonies and when diluted, the colonies decrease exactly parallel to it degree of dilution. But this ideal is not necessarily realized and especially the difference between the dilution of 10(-3) and 10(-4) mg/ml on the drug free medium and that of 10(-2) and 10(-3) on the drug containing medium is fairly remarkable: the former is not so large but the latter sometimes varies tremendously with the drugs and their concentrations. So it is necessary to use always two inoculations for all specimens and the resistance is calculated on the medium inoculated with the same doses, for that, colonies on the control must be countable and suitable number that is 50-300. Further too concentrated solution like 10(-2) mg/ml must not be used for the proportion method. The selection of the most suitable two dilutions is specially important for this method. Original one is 10(-3) and 10(-5). Unfortunately we did not follow this formula and at first we adopted the combination of 10(-3) and 10(-4), then 10(-2) and 10(-4) finally 10(-2) and 10(-3) which was the worst. Now we searched for the dilution which gave the suitable number of colonies from our several thousand cases and found that 10(-4) was the most excellent and gave this number in 63%, next 10(-5) in 14%, and then 10(-3) in 7.2%, 10(-2) in only 1.0%. With the combination of 2 solutions 10(-3) and 10(-5)--original one--was most excellent (94.8%) then 88.4% with 10(-4) and 10(-5). The combination of 10(-2) and 10(-3) was worst, it gave only 8.9%. As the proportion method demands the most strict procedures for all cases, it is necessary as simplify as possible, thus in every day practice, only the drugs most frequently used (3 or 4 drugs) and one concentration for each drug could be examined. Further we discussed on the difference between DH-SM and SM, direct and indirect method and problem of plug. PMID- 1434322 TI - [Tuberculous meningitis in Japanese children between 1980-1991]. AB - We evaluated the clinical and laboratory findings of tuberculous meningitis admitted to Tokyo Metropolitan Children's Hospital from 1980 through 1991 retrospectively. They consisted of 26 patients (14 boys and 12 girls), and their age ranged from 4 months to 11 years. Seventeen patients were under 3 years of age. Mortality rate was 4% (1/26), and there were 13 patients with sequelae on discharge from the hospital, and 12 patients without any sequelae. The period to recover normal CSF findings was relatively long. Some cases which did not seem to respond well to chemotherapy at the initial stage, recovered from meningitis without sequelae. This suggests that it is not necessary to change the chemotherapy at the initial few weeks of therapy. The risk factors of poor prognosis were; age less than 2 years, decreased level of consciousness on admission, convulsion, CSF protein more than 70 mg/dl, and CSF glucose less than 20 mg/dl. Tryptophan reaction was not always positive. Chloride in CSF was not so important to diagnose tuberculous meningitis in children. For the proper diagnosis of tuberculous meningitis in children one should consider several factors such as tuberculin skin test, family history, chest X-ray findings and CSF study. BCG was inoculated in six children (three patients were under one year old and the rests were older than 4 years). In three patients under one year old BCG was seemed to be inoculated after Mycobacterium tuberculosis infection, and apparently not effective to prevent tuberculosis meningitis. We conclude that BCG vaccination is necessary in early infancy to prevent tuberculous meningitis. PMID- 1434323 TI - [Mycobacterium fortuitum pulmonary infection in a healthy 17-year-old man]. AB - A 17-year-old man was admitted with a 5-month history of intermittent dyspnea on exertion, 10 kg weight loss, cough, sputa and fever. He did not smoke, had no apparent underlying pulmonary disease, and was not immunocompromised. Mycobacterium fortuitum was cultured from sputa at admission. Chest radiograph showed many thin-walled cavities and infiltration in the bilateral middle and upper fields. Chest CT detected multiple cystic lesions that were not revealed in conventional X-ray. It was suggested that the formation of the cystic lesions was one of the predisposing factor of Mycobacterium fortuitum pulmonary infection in this patient. The pneumonic change improved after six-month treatment using isoniazid, rifampicin and streptomycin, despite in vitro resistance of the bacilli to all of these drugs. PMID- 1434324 TI - [A complication of bronchoscopical brushing cytology and biopsy for pulmonary tuberculoma]. AB - Although bronchoscopical brushing cytology and biopsy are useful tools for differential diagnosis of localized abnormal lung shadows, they have some complications, one of which is bacterial infection. The patient was a 42-year-old female with a RUL coin lesion on chest roentgenogram, which was diagnosed as pulmonary tuberculoma through the bronchoscopical examination. The exam. was followed, however, by perifocal lung abscess with a cavity, which was believed to be anaerobic infection, and cured rapidly with initial intensive chemotherapy including RFP. Prophylactic use of antimicrobial drugs, which are also sensitive to anaerobic flora, would be necessary for preventing or minimizing such complication after bronchoscopy. PMID- 1434325 TI - [Do very low density lipoproteins (VLDL) participate in atherogenesis?]. PMID- 1434326 TI - [Do calcium antagonists inhibit the development of arteriosclerosis?]. PMID- 1434327 TI - [Percutaneous pulmonary valvuloplasty in 135 patients]. AB - We present our 7 years experience with 135 pts aged 1.4-44 years (mean 10-yrs) in whom percutaneous balloon valvuloplasty (BPV) for congenital pulmonary stenosis was attempted. In 4 pts we failed to place the balloon at valvar level, in another four BPV was repeated so, 135 procedures in 131 pts were performed. Balloon diameter/pulmonary anulus diameter ratio (BD/PD) ranged from 0.9 to 1.85 (mean 1.37). In 10 cases double balloon technique was used. Immediate results: in the whole group of 131 pts the right ventricular-pulmonary artery gradient (RV PAG) was reduced from 74 +/- 42 to 34 +/- 34 mm Hg, and right ventricular systolic pressure (RVSP) decreased from 92 +/- 41 to 54 +/- 34 mm Hg just after BPV. 86 pts (65.6%)--group I, had good immediate result of BPV (RVSP less than 50 mm Hg). 4 of them had dysplastic pulmonary valves (DPVs). RV-PAG in 82 pts with normal valves decreased from 53 +/- 25 to 15 +/- 7 mm Hg right after BPV. In 45 pts (34.4%)--group II, immediate result of valvuloplasty was recognised as unsatisfactory (RVSP greater than or equal to 50 mm Hg): in 4 of them BD/PD was smaller or equal 1.2 (subgroup IIa); 34 others had significant subpulmonary obstruction (SPO) that appeared or increased after BPV (subgroup IIb); and in remaining 7, DPVs were noticed (subgroup II c).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434329 TI - [Should the patients with atrial fibrillation receive long-term anti-arrhythmia treatment after successful cardioversion?]. PMID- 1434328 TI - [Preventive pharmacological treatment after cardiac electroversion for atrial fibrillation following surgical treatment of heart defects]. AB - 265 patients (168 women, 97 men) after cardiac surgery (mitral valve replacement- 74 pts, mitral commissurotomy--158 pts, aortic valve replacement--6 pts, replacement of both valves--16 pts, closure of ASD--11 pts) were randomized after successful electro-conversion of atrial fibrillation to quinidine (63 pts), verapamil (56 pts), amiodarone (50 pts), digoxin (56 pts) or control group (40 pts). The groups were comparable regarding age, sex and mitral valve disease distribution, heart volume, echocardiographic left atrium size and time from cardiac surgery to electro-conversion. After one year sinus rhythm was still present in 43% receiving quinidine, 43% receiving verapamil, 40% receiving amiodarone, 22% receiving digoxin, 20% in the untreated group, and after two years in 14%, 11%, 20%, 0% and 0%--respectively. The treatment was discontinued because of side effects in 13% of pts in the quinidine group, 8% of pts in the amiodarone group and 4% of pts in the verapamil group. It is concluded that quinidine, amiodarone and verapamil compared with control group are significantly (p less than 0.05--after one year) more effective in preventing late relapses of atrial fibrillation. Digoxin is ineffective in preventing recurrence of the arrhythmia. There are no significant differences between quinidine, verapamil and amiodarone regarding its prophylactic efficacy. PMID- 1434330 TI - [Mitral valve prolapse. Atrial stimulation, ajmaline test and "pharmacological denervation" in the evaluation of ventricular repolarization]. AB - In patients with mitral valve prolapse syndrome (MVP) various electrophysiological abnormalities occur. There are convergent opinions concerning QT distance variability and the influence of autonomic nervous system on ventricular repolarization in this syndrome. In 38 MVP patients (group I) and 24 subjects without this abnormality (group II) ecg was recorded during transvenous right atrial pacing at baseline, after ajmaline administration and after pharmacological autonomic blockade (atropine + propranolol). The following ventricular repolarization parameters were analysed: QTe (distance to the end of T wave), JTe (distance between J point and the end of T wave--so called "pure repolarization"), QTdys (repolarization dispersion) and the corrected QTc.QTe during 90/min right atrial pacing was significantly shorter than QTc in both groups. QTc was abnormally prolonged (above 440 msec) in MVP group. Ajmaline administration prolonged QTe in group II only, whereas autonomic blockade resulted in marked shortening of QTe in MVP group. QTdys was significantly prolonged only after ajmaline administration in group II. Based on above results, the following conclusions are made: 1) Right atrial pacing technique may be used for calculating standardized QT distance, an alternative to corrected QT. 2) Ajmaline test is useless in ventricular repolarization estimations in MVP patients. 3) In MVP patients the influence of adrenergic system on ventricular repolarization at rest appears to be greater than in non-MVP subjects. PMID- 1434331 TI - [Anatomical correction of transposition of the great arteries in 7 newborn infants]. AB - In the presented article, the course and results of anatomical correction of transposition of great arteries (TGA) in 7 neonates (2 females and 5 males) with mean body mass of 3250 g and 2 to 5 days old (mean 3 days) are reviewed. Surgery was performed in moderate hypothermia. St. Thomas cold cardioplegia was used. Mean aortic clamping time was 70 min (55-115), and the time of extracorporeal circulation was 165 min (117-210). Low cardiac output in all patients in the postoperative period required prolonged mechanical ventilation and positive inotropic drugs. Out of 7 patients operated, two died (29%). The cause of death in both cases was myocardial ischemia of right ventricle. The other 5 patients were discharged after healing of operational wound. In the control echocardiographic examination performed 3 to 12 months postoperatively, apart from one case of moderate pulmonary artery stenosis, no other haemodynamically significant complications were noted. PMID- 1434332 TI - [Pregnancy and labor in women with acquired heart defects]. PMID- 1434333 TI - [Controversies regarding electric stimulation of the heart]. PMID- 1434334 TI - [Complex treatment concept of psoriasis vulgaris in childhood with integrated high altitude-climate therapy]. AB - A sample of 102 inpatient children with psoriasis demonstrated differences in appearance and treatment to the psoriasis of adults. The complex therapy concept is based on 5 elements with dermatologic, high-altitude climatic and psychological treatment. Important additional factors are pre-school and school activities and vocational assistance. Of utmost importance is an early step-by step education of the parents and of the psoriasis child about the disease. Medical treatment is effectively completed and optimised by an appropriate life style and multiple prophylactic activities in the premedical and environmental fields of the diseased. Dermatologists and pediatrists should aim at on-target and well-organised medical guidance of the young psoriatics. PMID- 1434335 TI - [Sensitization to house dust mites: importance and possibilities of allergen elimination]. AB - House-dust mite allergy (Dermatophagoides pteronissinus and Dermatophagoides farinae) is an important causative factor for allergic asthma or rhinitis in children. There is a clear relationship between the degree of allergen exposure and the subsequent development of asthma or the risk of sensitisation. It is therefore useful to know how intensive a patient is exposed to house-dust allergen. This can be managed either by counting all mites in the dust, by measuring of the content of Der p I and Der f I (major antigens of the two mites) per gram dust or using the Acarex test. These methods are also suitable for the control of sanitation measurements, e.g. avoidance of all dust sources in the bedroom and living-room, use of suitable materials for bedding, application of acaricide products and covering mattresses with polyurethane-coated materials. PMID- 1434336 TI - [Failure to thrive in young children--disorders of carbohydrate absorption?]. AB - We examined 31 formerly hypotrophic newborn children (birth weight < 5th Kyank percentile) with failure to grow in infancy (weight < 3th Prader percentile). The rates of digestion and absorption of carbohydrates were determined by segmental perfusion of the small intestine and compared to the results of 21 patients with florid coeliac disease. Despite the normal structure of the mucous membrane of the small intestine, the rates of absorption of glucose in 14 formerly hypotrophic children and, additionally, in 12 and 10 of these children, respectively, the rates of hydrolysis of lactose and sucrose were nearly as low as in patients with florid coeliac disease. The reduced absorption and digestion of carbohydrates, respectively, could be a cause of subsequent failure to grow in some of the hypotrophic newborn children. PMID- 1434337 TI - [Kinetics of vaccination antibodies against tetanus toxoid, diphtheria toxoid, measles virus, poliomyelitis virus and pneumococcus after allogenic and autologous bone marrow transplantation and booster vaccination. 2: Kinetics of vaccination antibodies against diphtheria toxoid after allogenic and autologous bone marrow transplantation]. AB - In the second part of the paper we report on the results of the diphtheria antitoxin valuation of 8 children after allogeneic bone marrow transplantation (BMT) with and without graft versus host disease (GvHD) as well as on the kinetics of the diphtheria antitoxin of 5 children after allogeneic BMT with and without GvHD and of 5 children after autologous transplantation. The antibody valuation was done by a cell-culture assay. Whereas the inspection of the isolated data gives the impression of a swift antibody decrease up to the non protective level from the 7th month after BMT, the kinetic tests are more highly differentiated. Besides rapidly decreasing values below the accepted protection rate of 0.01 IU/ml in the allogeneic transplanted groups, there are patients with positive antibody titres within an observation period of up to 24 months after BMT in the allogeneic as well as in the autologous transplantation group. PMID- 1434338 TI - [Treatment of atopic dermatitis with borage seed oil (Glandol)--a time series analytic study]. AB - The therapy of atopic dermatitis with highly unsaturated fatty acids has witnessed a renaissance in the last years. Therefore, a study was conducted with borage oil (Glandol), rich in highly unsaturated, so-called omega fatty acids, against palm seed oil as placebo in a total of 12 patients. Evaluation of the severity of the skin changes was done by means of the ADASI (Atopic Dermatitis Area and Severity Index)-score system described by us recently. The ADASI-scores, forming a time series, were analyzed by trend analysis methods. These methods allow an evaluation of the effectiveness of the therapy in each case. The analysis revealed that five out of seven patients treated with borage oil showed a favourable effect with regard to the skin changes assessed by the ADASI-score. In contrast, only one out of the five patients treated with placebo showed a significant improvement in skin changes. In view of the positive effect ob borage oil in patients with atopic dermatitis, a trial therapy for a certain period seems justified. Our study demonstrates both the value of our ADASI-scoring system as well as the advantages that time series or trend analysis methods might have for the evaluation of therapeutic effects in chronic skin diseases such as atopic dermatitis. PMID- 1434339 TI - [The 800 numbers in pediatric practice. Is psychosomatic disorder reimbursable?]. PMID- 1434340 TI - [Practice management aspects in pediatric practice]. PMID- 1434341 TI - [Neurolemmoma of the stomach]. PMID- 1434342 TI - [The successful surgical treatment of a rare complication of a benign esophageal neoplasm]. PMID- 1434343 TI - [A human life over the course of 22 years after a gastrectomy]. PMID- 1434344 TI - [The surgical treatment of a giant follicular lymphoma of the mediastinum (Brill Symmers disease)]. PMID- 1434345 TI - [Multiple carcinoids of the small intestine]. PMID- 1434346 TI - [Fibrosarcoma of the gastrocolic ligament]. PMID- 1434347 TI - [A combined operation in cancer of the cecum, aneurysm of the abdominal aorta and calculous cholecystitis in an elderly patient]. PMID- 1434348 TI - [Leiomyosarcoma of the small intestine]. PMID- 1434349 TI - [The resection of the liver with a plasma scalpel for solitary cancer metastases]. PMID- 1434350 TI - [Neurinoma of the lesser omentum]. PMID- 1434351 TI - [An unusual location of an osteoblastoclastoma]. PMID- 1434352 TI - [Lymphogenous metastasis and lymphadenectomy in stomach cancer]. PMID- 1434353 TI - [Combined resections in the surgery of lung cancer]. AB - Operations were performed on 3,313 patients for lung carcinoma in the Department of Surgery of the Lungs and Mediastinum of the National Research Center of Surgery, AMS USSR, from 1963 till 1.01.90. Among these patients 263 (7.9%) were treated by combined operations (resection of the lung together with part of the chest wall, trachea and its bifurcation, pericardium, diaphragm, superior vena cava, pulmonary artery, aorta, and atrium, and also with removal of metastatic lymph nodes of the contralateral lung). Three types of combined resections were carried out--vasculo-atrial, tracheo-bronchial, and parieto-diaphragmatic. Postoperative complications developed in 38.6% of patients. Intraoperative mortality was 1.5%, 13.9% of patients died after the operation. More than 5 years survived 21.8% of patients who underwent operation, more than 10 years 10.2%, and more than 15 years 5.6% of patients. PMID- 1434355 TI - [Extracorporeal biliary lithotripsy]. PMID- 1434354 TI - [The immunogenicity of different organs and the characteristics of immunosuppressive therapy during their allotransplantation]. PMID- 1434356 TI - [Essays on surgical diagnosis]. PMID- 1434357 TI - [The surgical treatment of patients with benign tumors and cysts of the mediastinum]. AB - The article deals with the experience in the surgical treatment of 315 patients with benign tumors and cysts of the anterior (in 58.8%) and posterior (in 41.2%) mediastinum. Various methods of intervention--transpleural and extrapleural--were employed. Some extrapleural approaches were developed at the clinic. The clinical postoperative data show that they cause little trauma. Indications in observance of which these approaches may be considered optimal are determined. PMID- 1434358 TI - [The use of the CO2 laser in the surgical treatment of benign breast diseases]. AB - Benign diseases of the breast of a noninflammatory character are a widely encountered pathological condition. Most surgeons claim the nodular form of mastopathy to be a precancer. Sectoral resection of the breast is the only grounded and justified method for its treatment. Unfortunately, wound complications develop often in the postoperative period, which increases the duration of in-patients treatment, prolongs the period of restoration of the working capacity, and leads to the formation of coarse scars which disfigure the breast. Dissatisfaction with the results is also explained by the development of a recurrence in a certain percent of cases. The results of treatment in 2 groups of patients were compared: patients of the main group (group 1) were operated on with the use of the CO2-laser, those of the control group (group 2) were operated on by the traditional method. Analysis of the results of treatment shows that the modified method of sectoral resection has advantages over the traditional method and can therefore be recommended for wide introduction into clinical practice. PMID- 1434361 TI - [Risk in the surgical and general plan (a lecture)]. PMID- 1434359 TI - [Puncture aspiration biopsy under ultrasonic control in the diagnosis of breast neoplasms]. AB - The authors studied the results of sonography of the breast and zones of regional lymph drainage in 15,973 patients. In 154 of them puncture aspiration biopsy was conducted under ultrasonic control. Breast carcinoma was found in 23 patients, in 2 of them the tumor was not palpable. The examination was performed on the Aloka SSD-630 apparatus. The sonographic picture was that of a structure with diminished echogenic properties, irregular notched contours, and non-uniform echo signals from the internal structures. Echography with puncture biopsy made it also possible to reveal the presence of nonpalpable axillary metastatic lymph nodes and to establish the precise differential diagnosis of benign and malignant intraductal tumors. The method of puncture aspiration biopsy under control of ultrasonic examination is highly effective in the differential diagnosis of breast carcinoma. PMID- 1434360 TI - [Benign symmetrical lipomatosis with predominant localization in the neck area (Madelung's disease)]. AB - Eighty-eight males with benign symmetrical lipomatosis (BSL) were subjected to complex examination, 68 of them were operated on. BSL is a slowly progressing disease marked by the development of nonencapsulated symmetrical fatty masses mainly in the region of the neck. It usually occurs in males at the age of 35-50 years. Chronic alcoholic intoxication was found in 46 (48%) patients, 36 (41%) patients had various functional disorders which caused invalidation in 5 (5.7%) cases. A familial character of the disease was revealed in four (4.5%) cases. A classification of the disease is suggested which takes into account the functional disorders and the degree of development of the lipomatous masses in the neck. The author discusses the stages of the treatment, the surgical anatomy, a method for revealing the salivary glands in the lipomatous tissue by staining them with methylene blue solution, the operative techniques, the complications and their prevention, and the late results of surgical treatment. Satisfactory esthetic and functional results were achieved in 94.2% of patients who were operated on. PMID- 1434362 TI - [The potentials for the organ-preserving treatment of early stomach cancer]. AB - The oncological substantiation of endoscopic and economical surgical treatment of T1N0-1M0 gastric carcinoma in 46 patients was appraised. The results were studied with due regard for the peculiarities of early gastric carcinoma (EGC) revealed in 290 patients after standard surgical management. It was established that organ preserving treatment of ECG is possible--5-years survival was 96.2%. Endoscopic removal can be considered radical only in T1P1 tumors without invasion of the lymphatic vessels of the wall and was of a multistage character in 86.2% of cases. Careful surveillance after its completion is necessary. Surgical treatment in indicated in repeated recurrences; they were encountered in 44.8% of cases. The causes of the recurrences were noncoincidence of the macroscopic and histological boundaries of the tumor (33.6%), multicentric growth (30.4%), and invasion of the submucosa. Metastases are encountered in the lymph nodes in 9.1% of cases in economical treatment. In T1N0-1M0P1-2 carcinoma, absence of multicentric growth, and III degree dysplasia in the surrounding mucosa (reflecting increased risk of multicentric growth) the volume of organ resection may be limited on condition that P1 lymphadenectomy is performed. The results of organ-preserving treatment are comparable with those of surgical treatment conducted in a standard volume. PMID- 1434363 TI - [The choice of an optimal variant in the reconstructive stage of gastrectomy]. AB - The authors analyse 40-year experience in gastrectomy and extirpation of the gastric stump in carcinoma of the stomach. Operations were performed on 742 patients. The results show that the mechanical suture has advantages over the manual suture in the formation of the esophago-intestinal anastomosis. The functional results were found to be best when the continuity of the gastrointestinal tract was restored by establishing the esophago-intestinal anastomosis with a loop of the small intestine isolated according to Roux. Comparative appraisal of end-to-end and end-to-side esophago-intestinal anastomoses revealed the advantages of the last-named in relation to the incidence of postoperative complications and total outcomes. The effect of the surgeon's qualification on the frequency of postoperative complications is discussed. PMID- 1434364 TI - [The surgical and combined treatments of locally disseminated cardioesophageal cancer]. AB - The article deals with the experience in the treatment of more than 1,000 patients with cardioesophageal carcinoma in 1965-1989. The authors note increase of surgical activity and widening of indications for operative treatment at the cost of patients of the old age groups and those with locally-extending forms of the neoplastic process. In distinguishing the term cardioesophageal carcinoma the authors insist on the community of the surgical tactics and operative methods in carcinoma of the cardia extending to the esophagus and in esophageal carcinoma spreading to the stomach. Improvement of the results of tre treatment the authors attribute to the perfection of the methods of lymphodissection and formation of esophageal anastomoses. The authors claim that the development of effective methods of combined treatment underlies the prospects of improving the late-term results. Experience in preoperative hypoxyradiotherapy, adjuvant postoperative chemotherapy, and preoperative regional intraarterial polychemotherapy is analysed. PMID- 1434365 TI - [The surgical treatment of malignant stomach ulcers]. AB - The authors analyse the specific features of the clinical picture, diagnosis, pathomorphological changes and surgical treatment in 52 patients with gastric ulcer which underwent malignant degeneration. It is noted that malignancy occurs most frequently in close vicinity to the ulcerative defect and rarely in the mucosa beyond the ulcer. The morphostructural reorganizations are determined to a certain degree by the peculiarities of extension of the tumor along the mucosa and the organ as a whole. The authors discuss the principles of the choice of the method for treatment according to the findings of pathomorphological examination of biopsy material and the results of emergency intraoperative examination. Even if the merest suspicion of malignancy of the ulcer arises, the operation should be conducted with observance of all oncological principles. Postoperative mortality was 3.8%, complications occurred in 7.7% of cases. Five-year survival was 84.6% in the absence of metastases and the presence of carcinoma cells within the limits of the mucosa and 12.5% among cases in which metastases were found during the operation. Attention is drawn to the principles of regular medical surveillance over patients receiving nonoperative treatment for gastric ulcer. PMID- 1434366 TI - [The groups at risk for a recurrence of rectal cancer after radical operations]. AB - The article discusses a group of patients with rectal carcinoma who underwent radical operations at the Scientific Research Institute of Proctology in 1982 1983. The terms and frequency of rectal carcinoma recurrences are analysed and the factors influencing these indices are studied. The results made it possible to form a group with a risk of a recurrence among patients with carcinoma of the rectum and suggest new schedules of regular medical observation over these patients with consideration for the risk group. PMID- 1434367 TI - [The surgical treatment of benign smooth-muscle tumors of the rectum]. AB - From analysis of the surgical treatment of 36 patients with rectal leiomyoma the authors suggest and substantiate the indications for various types of operative interventions according to the size and location of the tumor. The late-term results of the treatment were studied in all patients who underwent surgery and a brief review of literature on the methods of diagnosis and surgical management of benign smooth-muscle tumors of the rectum is given. PMID- 1434368 TI - [Kidney cancer morbidity in a population group under continuous observation in dispensary care]. AB - Information on kidney carcinoma case rate among a contingent kept under continuous observation and subjected to regular medical examination is discussed. The authors had 390 cases under observation which allowed them to estimate the case rate according to the patients' sex and age group. A 5.8-fold increase of the case rate in a period of 15 years was found. In males it increased from 0.31:1000 to 1.8:1000, and was highest in the 50-59-year age group. Among females the kidney carcinoma case rate increased 2.5-fold in 15 years; it was highest among females aged over 70 (3.20:1000) and was 2.6 times higher than the case rate in the 50-59-year age group and 4.5 times higher than that in the 40-49-year age group (0.32:1000 and 1.44:1000, respectively). Kidney carcinoma takes a steady 6th place in the morbidity structure. Ultrasonic diagnosis of kidney carcinoma is the most effective method. The authors point out that study of the case rate of malignant kidney tumors is very important for elaborating the volumes of examination. PMID- 1434369 TI - [The characteristics of kidney cancer invasion of the major retroperitoneal veins]. AB - The authors discuss the variants of kidney carcinoma thrombus invasion of the major retroperitoneal veins, up to the right atrium, on basis of the literature data and their own findings during prosectorial (4) and clinical (7) practice. They emphasize that carcinoma may not only invade the large veins in the cardial direction in the blood flow but may also spread against the flow into the contralateral renal, hepatic, iliac, and other veins, which is illustrated by examples. Symptoms of cardiovascular insufficiency with venous congestion in the liver and lungs with the formation of red infarcts, the development of ascites and even with fibrous changes in the organs and insufficiency of their function came to the forefront in mild clinical signs of the main focus of affection. According to the clinical material, the incidence of thrombi in the inferior vena cava was 3.9%. All the thrombi in operated on patients were below the diaphragm and measured up to 11 cm in length. Histologically the thrombus consisted of formed elements of the blood, tumor cells (adenocarcinoma of light cells) which were inside it and fibrin which was outside. The thrombi grow slowly and undergo organization and vascularization. PMID- 1434370 TI - [Tendoplasty of the fingers and the restoration of the skin-fatty layer of the dorsal surface of the hand in boutonniere contracture]. AB - In the period from 1983 to 1990 operations were conducted on 63 patients with postburn boutonniere contracture of 116 fingers. In 19 patients (42 fingers) tendoplasty of the extension apparatus of the fingers was carried out with simultaneous restoration of the dermatoadipose layer on the dorsal surface of the hand with an inguinal or dermatoadipose graft. In 39 patients the tendon of the extensor digitorum muscle was injured over several proximal interphalangeal articulations. A new method for treating boutonniere contracture is suggested. It is based on restoration of the continuity of the central fasciculus and the normal position of the lateral fasciculi with a single tendon autograft. The suggested method produced good results in 90% of cases, i.e. in all cases in which a sufficient volume of passive movements at the proximal interphalangeal articulation was restored in the preoperative period. PMID- 1434371 TI - [The combined treatment of acute suppurative diseases of the fingers and hand using decamethoxin]. AB - The authors discuss the results of complex treatment of 286 patients with acute pyoinflammatory diseases of the fingers and hand with the use of a new Soviet produced antiseptic decametoxin. Panaris was diagnosed in 196 (68.5%), phlegmons and abscesses in 82 (29.7%), furuncle in 6 (2.1%) and carbuncle in 2 (0.7%) patients. 224 (78.4%) patients received out-patient and 62 (21.6%) in-patient treatment. The authors established that as the result of the applied complex treatment with the use of various antiseptic compositions containing decametoxin the mean duration of treatment was 7.8 days. The article discusses the causes of the disease, the methods of operative treatment, and management of patients in the postoperative period. PMID- 1434372 TI - [The technic of esophageal extirpation with one-stage esophagoplasty using a stomach tube]. AB - The article deals with the technical aspects of operation for extirpation of the esophagus through a cervico-abdominal approach in carcinoma (133 operations) and benign esophageal strictures (117 operations) with one-stage plastics by means of an isoperistaltic tube formed from the greater curvature of the stomach. The relative safety (2.8% of patients died) and high efficacy of the described operation allow it to be recommended for wide introduction into the practice of institutions engaged in surgery of the esophagus. PMID- 1434373 TI - [An analysis of the reasons for relaparotomy in the surgical clinic]. AB - The results of surgical treatment of 4,078 patients who underwent operation in 1985-1989 were studied. Due to the occurrence of complications in the early postoperative period, 182 relaparotomies were carried out in 164 patients. The main indications for relaparotomies were advanced underlying disease, surgical errors (tactical, technical), changes of the patients' immune status. Early diagnosis, timely operation with the use of technically correct manipulations, and the application of a full complex of intensive therapy measures in the postoperative period are important in the prevention of complications. PMID- 1434374 TI - [A system for the clinico-immunological prognosis of infectious-inflammatory complications in planned surgery]. AB - Postoperative infectious complications in planned surgery are a pressing problem. The preoperative condition of the patient and his immune system play an important role in their development. Fifty patients of the "risk" group were selected from the standpoint of classification of the etiological factors of secondary immunodeficiency states. Fifteen patients who had no symptoms classified as SIDS risk factors formed the control group. The immune status was examined before and on the third day after the operation in all patients of the main and control groups. Various infectious complications developed after the operation in 23 patients of the risk group. No such complications occurred in the control group. The preoperative immune status of the risk group patients differed significantly from that of the controls in 13 of 19 parameters. The patients of the main and control groups formed the instructing selection. An expert system of preoperative clinico-immunological prognostication of postoperative infectious-inflammatory complications was created on oasis of the methods of the theory of image recognition and instructing selection. The system was tested in a direct clinical experiment on 66 patients. The prognoses were correct in 89% of cases. It was thus proved that symptoms classified as SIDS risk factors influence the initial immunity status and the course of the postoperative period in planned surgery. An accurate, sensitive, and specific method for prognosticating postoperative infectious complications is suggested. PMID- 1434375 TI - [Colored light stimuli in ERG for differential diagnosis of cone dystrophies]. AB - We recorded electroretinograms (ERG) with white and color stimuli in normal persons and four patients with cone dystrophies. Kodak Wratten-filters in blue, blue-green, green, yellow and red were used for the color flashes. ERGs to all color stimuli were recorded at dark and light adapted conditions with different stimulus intensities, to 30 Hz flicker stimulation and with special filtering for oscillatory potentials. Selective blue cone-responses were obtained using strong blue flashes at a yellow background. Patients with cone dystrophies showed slightly to moderately reduced responses at dark adaptation to blue, blue-green, green and yellow stimuli. Red stimuli elicited only small responses with a markedly delayed b-wave implicit time. The light adapted recordings, flicker responses and oscillatory potentials were reduced to all color stimuli. However, differences between patients with cone dystrophies could be detected concerning the responses to red and green. In two patients the responses were reduced to the same degree to all color stimuli. Another patient had very small responses and no oscillatory potentials to red, but his responses were only moderately reduced to green. A patient with combined red-green cone and rod dystrophy had a blue cone hypersensitivity. Responses to blue and blue-green were large at all stimulus conditions, but responses to all other stimuli were much smaller. The blue cone ERG showed a prominent blue cone response. ERG recording to colored stimuli allows a separation of retinal dysfunction in patients with cone dystrophies. PMID- 1434376 TI - [Multiple evanescent white dot syndrome]. AB - A 38-year-old male patient experienced a unilateral visual acuity decrease to 20/60 and showed white dots at the level of the retinal pigment epithelial interface characteristic of multiple evanescent white dot-syndrome. Fluorescein angiography demonstrated early hyperfluorescent defects and some late staining. In spite of improvement of the visual acuity and the alterations of the fundus, an enlargement of the blind spot and some sharply demarcated depigmentations of the retinal pigment epithelium remain. This case shows, that already at the beginning of symptoms the characteristic white dots may be present. Enlargement of the blind spot and depigmentations of the retinal pigment epithelium may remain as defects after multiple evanescent white dot-syndrome. PMID- 1434377 TI - [Detection of phosphoglucomutase in the cornea and corneal cell cultures using isoelectric focusing and enzymatic stain methods]. AB - PGM-1 and its isoenzymes had been studied in the human cornea, in cornea cell cultures, in erythrocytes and lymphocytes. Qualitative and quantitative comparisons between cornea of healthy persons and cornea cell cultures of patients with cornea dystrophies showed differences between certain phenotypes and their signals of activity. PMID- 1434378 TI - [Cardiac myxoma with central retinal artery occlusion, hemiparesis and epileptic seizure in a 9-year-old patient]. AB - A cardiac myxoma is a very rare cause for a central retinal artery occlusion (CRAO). We report the case of a nine-year-old boy who had an epileptic seizure, the computer-tomographically suspected diagnosis was intracerebral granulomas of unknown etiology. Five months later he suffered an acute hemiparesis and a CRAO. Through echocardiography the diagnosis of a cardiac myxoma was determined. This case shows the importance of the differential diagnosis "cardiac myxoma" in cases of central retinal artery occlusion in young patients especially with additional neurological disorders. PMID- 1434379 TI - [Reversible mydriasis and cycloplegia after isocyanate exposure]. AB - We saw three patients working in the production of polyurethanes, who showed mydriasis and cycloplegia of unknown origin. In one patient there was also a transient opacification of corneal stroma. After discontinuation of working both mydriasis and cycloplegia resolved completely within 3-5 days. Because of the history and the analysis of chemical reactions involved in the production of polyurethanes there is strong evidence that both mydriasis and cycloplegia have been caused by topical and (/or) systemic intoxication with the aryl diet of the isocyanate molecule. PMID- 1434380 TI - [Congenital facial hemiatrophy. Report of two pediatric cases]. AB - In facial hemiatrophy two different types are known: the progressive acquired type, which is relatively more common, and the rare congenital non progressive form. Two children--both with congenital facial hemiatrophy--are presented, both showed a (horizontally and vertically) smaller lid fissure and antimongoloid configuration of the lid. In addition in one case we could observe: small corneal diameter, staphyloma posticum, paving stone degeneration of the retina, convergent strabismus, and vertical deviation, in the other case: ptosis, major astigmatism, and latent divergent strabismus. PMID- 1434381 TI - [Endogenous candida endophthalmitis in a drug dependent patient: intravenous therapy with liposome encapsulated amphotericin B]. AB - We report this exemplary case of a drug addict with candida endophthalmitis where we used the new form of amphotericin B, encapsulated in liposomes. We were able to reconfirm the reduced number of side effects and the minimized nephrotoxicity reported by authors of other specialties. In our patient, a reduction or elimination of the yeast was probably achieved, nevertheless, he developed a traction retinal detachment. In future cases of fungal endophthalmitis, we recommend liposomal amphotericin B in higher doses. PMID- 1434382 TI - [Further development of a streak retinoscope with calibrated collimator]. AB - Development and rationale of a new streak retinoscope have been discussed in an earlier paper. In contrast to classical retinoscopy this retinoscope determines the refraction by forming the narrowest streak in the test person's pupil with a calibrated collimator. In addition to the first prototype the extension of the lamp according to variation of the refraction is measured electronically and the data are transposed into a computer. This allows to freely choose a working distance in a range from about 30 to 120 cm and therefore it is possible to examine restless patients. Accuracy of the measurement was less than or equal to 0.25 D for Ametropia from -0.5 to 5.0 D in a working distance of 30 cm or from 4.0 to -1.5 D in 100 cm. In most persons it is not necessary to use additional glasses during refraction by choosing the adequate distance. Therefore this method can help to refract kids and other persons which could not be refracted by use of glasses. In addition this method excludes the accommodation of the patient as apposed to regular refractometers. PMID- 1434383 TI - [64th meeting of the Rhein-Main Ophthalmologists. Main theme: Diabetes and the eye. Frankfurt am Main, 5 October 1991]. PMID- 1434384 TI - [Comment on cataract incidence of sulcus versus capsular sac fixed posterior chamber lenses by G. A. Vilhjalmsson, B. C. Lucas]. PMID- 1434385 TI - [Success of retinal surgery comparing phakic and pseudophakic eyes with reference to preoperative findings and the kind of lens implant]. AB - We analyzed retrospectively 597 eyes over a minimum follow-up of 6 months and compared the results of pseudophakic eyes with phakic eyes. The repair of pseudophakic retinal detachment is more difficult than the surgery in aphakic retinal detachment. Pseudophakic retinal detachment had a more advanced retinal detachment and PVR-stages at the time of diagnosis. Localisation of the tear was more complicated and the surgery was more invasive than in phakic eyes. In 61.2% the repair was for pseudophakic eyes with posterior chamber lens 78%, with anterior chamber lens 81.8% and for iris-fixated IOL's 75%. Compared to this, the anatomic reattachment rate in phakic eyes was 94.8%. The pseudophakic group had less favorable visual results. PMID- 1434386 TI - [Ocular findings in infection with Borrelia burgdorferi]. AB - During the years 1988 to 1990 ten patients were observed in the eye clinic of RWTH Aachen with ocular findings of infection with Borrelia burgdorferi. 6 of them showed neuro-ophthalmological signs, 4 had uveitis. In both groups recent infections were documented in fresh and chronic stages of the disease, lasting longer than one year. The various clinical pictures of the disease following infection with Borrelia burgdorferi are described. As a vaccination against Borreliosis is not yet available, it is important to detect the antibodies against Borrelia burgdorferi early enough, to initiate an effective treatment. PMID- 1434387 TI - [Errors of monocular localization in strabismic amblyopia. Two-dimensional distortion]. AB - Spatial distortions, i.e. spatial localization errors, and precision of localization were measured monocularly in the central visual field of 7 normal observers, 17 strabismic amblyopes and 2 anisometropic amblyopes. The task of the subjects was to construct circles of 2 degrees, 4 degrees and 6 degrees radius around a fixation point, using the dominant and the amblyopic eye in turn. Normal observers set distances on the vertical meridian smaller than distances on the horizontal meridian. Anisometropic amblyopes showed localization errors and variances similar to those of normal observers. The amblyopic eyes of strabismic observers with a large angle strabismus and deep amblyopia showed significant, individually different localization errors correlating with the depth of amblyopia. Strabismics with microstrabismus exhibited parallels between monocular localization and dichoptic retinal correspondence. PMID- 1434388 TI - [Objectified measurement of eye lens transparency in elderly probands. Results of a Scheimpflug photography study over the course of three and a half years]. AB - Lens density has been followed-up in 32 healthy volunteers (mean age 65 years) over a period of 3.5 years. The negatives of Scheimpflug-photos (Topcon SL-45) were evaluated by linear microdensitometry in three measure planes (Joyce Loebl 3 CS). Correlation coefficients, curves of regression as well as calculations of the percentage of density change made obvious, that a minimal increase in lens density occurred in the anterior cortical region. PMID- 1434389 TI - [Inflammation of omental appendices of the large intestine]. PMID- 1434390 TI - [Detoxication methods in pancreatogenic enzymatic peritonitis]. AB - A therapeutic response was analyzed in 536 patients with acute destructive pancreatitis complicated by pancreatogenic enzymatic peritonitis. All the patients had the syndrome of endogenic intoxication and underwent intensive resuscitation with protease inhibitors, cytostatic agents, antibacterial, desensitization and detoxication treatment. If indicated, the patients with pronounced endogenic intoxication were subjected to forced diuresis, abdominal laparoscopic drainage and intraperitoneal dialysis, drainage of the thoracic lymphatic duct, hemosorption. Routine surgical intervention was performed. Up to 11% fell the general lethality due to a differentiated therapeutic approach. PMID- 1434391 TI - [Prognostication in pancreatic shock in patients with acute pancreatitis during enzymatic toxemia]. PMID- 1434392 TI - [Clinico-morphological correlations of chronic pseudotumorous pancreatitis and cancer of the pancreas]. AB - Examination of 57 pancreatic cancer patients and 40 subjects with chronic pseudotumorous pancreatitis revealed a resemblance in the clinical picture and uniform changes in the blood levels of pancreatic enzymes in both groups. Histological examination of 32 patients who expired from pancreatic cancer revealed total chronic pancreatitis manifested in inflammatory infiltration, focal destruction of the duct epithelium, atrophy, interstitial, periductular and perivascular sclerosis, dilatation of the ducts and pancreolithiasis. The character of the morphological changes in patients with pancreatic cancer corresponds to both primary and secondary origin of pancreatitis. Similarity of clinical manifestations and uniform changes in the blood content of pancreatic enzymes could be explained by the presence of chronic pancreatitis concurrent to pancreatic cancer. PMID- 1434393 TI - [Possibilities of the use of trypsinogen activation peptide in the pancreatic tissue in the diagnosis of pancreatic necrosis]. AB - The test of peptide of trypsinogen activation (PTA) in various biological media is a principal new diagnostic test for acute pancreatitis. PTA levels in the pancreatic tissue and the plasma of the blood in acute experimental pancreatic necrosis reflects the process of the pathological activation of trypsin in the diseases focus and confirms the source of higher levels of activation peptide in the blood flow. Together with the values of other enzymatic systems of the pancreatic gland the discussed value permits one to make a more precise assessment of the mechanism and stages of autodigestive processes which develop in acute experimental pancreatitis. PMID- 1434394 TI - [Course and therapy of nonpancreatic complications of chronic pancreatitis]. AB - Out of 647 patients with chronic recurrent pancreatitis followed up for 10-12 years 27 patients (4.2%) developed symptomatic gastroduodenal ulcers, 29 (4.5%) multiple gastroduodenal erosions. Ulcers and erosions emerged in patients with pronounced pancreatic bicarbonate insufficiency. Sucralfate treatment produced the best effect, while almagel plus vicalin were superior to gastrozepin. Relapses of ulcerogenesis were registered in 8 cases, multiple erosions in 11 cases, left pleural exudate in 8 cases in the presence of chronic pancreatitis exacerbation. Pancreatocardiac syndrome with cardialgias, a trend to arterial hypotonia, reduced voltage of ECG waves, occasional extrasystolic arrhythmia occurred in 45 patients (7%). It is shown that metabolic disorders of biogenic amines and lowered blood levels of insulin and C-peptide may underlie pathogenesis of pancreatocardiac syndrome. PMID- 1434395 TI - [Prognostic significance of cytochemical and functional activity of blood lymphocytes in patients with peptic ulcer and the presence of Helicobacter pylori]. PMID- 1434396 TI - [Reactive arthritis in young men in organized collectives]. AB - The authors followed up 398 young males with reactive arthritis who had been admitted from organized collectives to hospital settings. Only one third of them could connect the development of reactive arthritis (ReA) with a survived infection: acute nasopharyngeal (26%), acute enterocolitis (7%), urethritis venerea (1%). Analysis of the clinical picture demonstrated that in case of indefinite ReA etiology together with the signs of myocardiac involvement one should not only exclude the presence of rheumatic attack but also to establish a possible relation of the disease with a prior survived poorly manifest intestinal infection. This fact should be taken into account if in the collectives, where from the patients were hospitalized, epidemic outbreaks of acute dysentery or cases of ReA and Reiter's disease etiologically connected with manifest intestinal infection were documented. Postenterocolitic origin of ReA could be suspected in patients with its continuous course and resistance to antiinflammatory therapy in whom arthralgia was preserved for a long time as was joint rigidity after a subsidence of joint changes due to the effect of acute inflammation. Besides, the detection of certain features of the articular syndrome and separate extraarticular signs characteristic of Reiter's disease and other conditions which comprised the group of seronegative HLA--B27-positive spondyloarthropathy are of high diagnostic value. PMID- 1434397 TI - [Indicators of lipid metabolism and lipid peroxidation system in patients with different types of lesions of the vessels of the lower limbs]. AB - A total of 66 patients were investigated with IR imager and television capillaroscopy for the blood circulation in the vessels of low extremities as well as for the values of lipid metabolism and the system of lipid peroxidation. According to the status of the vascular system in the low extremities the examinees were divided into the groups with the normal status of the vascular system, the groups with the signs of venous insufficiency, microcirculatory disorders and atherosclerosis of major vessels. With the disorders of microcirculation in low extremities staged increments in the atherogenic shifts in the exchange were demonstrated. It was suggested that atherosclerotic changes in the arteries could be preceded with the hemodynamic changes in the venous and capillary systems due to rheological disorders due to the development of hypercoagulation which accompanied dyslipoproteinemias and other atherogenic shifts in the metabolism. PMID- 1434398 TI - [Ultrasonic methods of diagnosis of late complications after reconstructive surgery of the aorta and major arteries of the lower limbs]. AB - Long-standing results were studied in 587 patients who sustained reconstructive vascular surgeries when aged under 16 years (the average age was 6 years and 4 months). Out of them 141 patients faced the necessity of repeated surgeries: in 115 (81.6%) patients the extremity function was preserved, in 19 (13.5%) a repeated amputation was performed, 7 patients (4.9%) expired. All those operated on had been actively followed up with the use of periodical instrumental investigation which included dopplerography and ultrasonic angiography. High significance of ultrasonic technique was proved as the use of it permitted one to detect late complications on the early stages of their development and perform surgical corrections before the development of life-threatening complications. Therefore repeated preventive surgeries were performed in 53 patients, 52 of them were a success. Repeated amputations were performed in 1 patient. All those operated on survived. PMID- 1434399 TI - [A case of photodermatosis after long-term use of amiodarone]. PMID- 1434400 TI - [A case of toxic fibrosing alveolitis caused by ammonia vapors]. PMID- 1434401 TI - [Ochronosis with severe lesions of joints and the cardiovascular system]. PMID- 1434402 TI - [Bronchial asthma and broncho-obstructive syndromes]. PMID- 1434403 TI - [Acanthosis nigricans in patients with stomach cancer]. PMID- 1434404 TI - [Chronic cholecystitis with manifestations of hypomotor dyskinesia]. PMID- 1434405 TI - [Quantitative and qualitative changes in blood leukocytes in patients with duodenal ulcer and their diagnostic significance]. PMID- 1434406 TI - [Treatment of patients with initial manifestations of cerebral circulation insufficiency in vasomotor dystonias]. PMID- 1434407 TI - [Gilbert's syndrome: experience with a follow-up of an outpatient group]. PMID- 1434408 TI - [Oncological aspects of ambulatory care of patients with diseases of the thyroid gland]. PMID- 1434409 TI - [Diffuse toxic goiter]. AB - Diffuse toxic goiter is a common disease of the thyroid gland. As organospecific autoimmune condition the disease is not infrequently combined with endocrine ophthalmopathy and in this connection a more precise preparation of the patients to surgery is found to be mandatory. Elderly persons demonstrate atypical patterns of the disease course (insignificant enlargement of the gland, manifest depression, isolated cardial disorders without other symptoms of thyrotoxicosis, resistance to thyrostatic treatment). The patients need a life-long dispensary follow-up as diffuse toxic goiter is a condition of a relapsing type. PMID- 1434410 TI - [Language of scientific works and lectures]. PMID- 1434412 TI - [Conservative therapy in chronic renal failure]. PMID- 1434411 TI - [Organization and methodology of the process of examinations in internal diseases in higher education]. AB - The authors developed a system for examinations at the stage of postgraduate advanced training for therapists which included fundamental and practical classes. Fundamental classes are presented with certain tests with regard to the curriculum while the practical ones are based on the evaluation of professional clinical skill demonstrated at the examination of the patient. The developed system is realized with the help of computerized programmes CM-4. High objectivity and the wide spectrum of the programme evidence the practicability of the methods developed in the evaluation of knowledge in therapists. PMID- 1434413 TI - [State and perspectives of the treatment of patients with malignant neoformations]. PMID- 1434414 TI - [Career planning in nursing]. PMID- 1434415 TI - [Education in the new provinces]. PMID- 1434416 TI - [Nursing in the extended Europe. Aspects of education in nursing, pediatric nursing and geriatric nursing]. PMID- 1434417 TI - [For discussion: nursing insurance and nursing shortage]. PMID- 1434418 TI - [Documentation notes for ambulatory care. A study by the professional group "Ambulatory Care" of the German Federation of Nurses, Bavaria]. PMID- 1434419 TI - [Nursing documentation in psychiatric nursing? A questionnaire project by the professional group Psychiatry in the Bavarian section of the German Nursing Federation]. PMID- 1434420 TI - [The Hannover office of the German Nursing Association]. PMID- 1434421 TI - [Relief from non-nursing activities. Report on a project]. PMID- 1434422 TI - [Publicity for nursing]. PMID- 1434424 TI - [The aged patient in endoscopy]. PMID- 1434423 TI - [Quality assurance in intensive care. From controlled emergency to planned care]. PMID- 1434425 TI - [Changes in the operating room service. Reflections of an operating room administrator from the new federal provinces]. PMID- 1434426 TI - [Interprofessional cooperation by nursing teams]. PMID- 1434427 TI - [The Bad Schwartau office of the German Nursing Society]. PMID- 1434428 TI - [Europe--new chances for nursing?]. PMID- 1434429 TI - [Strike in public service--strike in nursing]. PMID- 1434430 TI - [Introduction of new coworkers]. PMID- 1434431 TI - [Continuing education "Nursing in Geriatric Rehabilitation". A model project of the Essen Educational Center of the German Nursing Association. Qualification for geriatric nursing, nursing specialist for geriatric rehabilitation]. PMID- 1434432 TI - [Professional stress for nurses. I]. PMID- 1434433 TI - [The summer festival. An event in long-term care]. PMID- 1434434 TI - [Humaneness and economic efficiency--tasks for the nursing professions aimed at the future]. PMID- 1434435 TI - [Nursing review. Interview by Krankenpflege with Karin Schroeder-Hartwig]. PMID- 1434436 TI - [Trends in buying for nursing concerns. Looking for work simplifying products]. PMID- 1434437 TI - [A new alternative for persons with loss of psychologic autonomy: validation]. PMID- 1434438 TI - [Questions about the professional role. A face to face complex]. PMID- 1434439 TI - ["Our health depends on our environment"]. PMID- 1434440 TI - [Buying--with ecological conscience]. PMID- 1434441 TI - [Preventive projects against poverty and disease: a place for children]. PMID- 1434442 TI - [75 years St. Gallen School for Pediatric Nursing. From infant nurse to specialist in pediatric nursing]. PMID- 1434443 TI - [Experiences with the voluntary home care organization in Israel. With an army of volunteers]. PMID- 1434445 TI - [The nurse facing an alcoholic patient. What attitude to take?]. PMID- 1434444 TI - [Swiss Society for Health Politics meeting on hospitals needing care. From sick house to health house]. PMID- 1434446 TI - [The Diogenes syndrome]. PMID- 1434447 TI - [End of the personnel shortage in Berne. Many are awaiting the recovery]. PMID- 1434449 TI - [Legal foundations. Part-time workers, auxiliaries and temporaries]. PMID- 1434448 TI - [Borders in everyday life]. PMID- 1434450 TI - [Democracy before all else]. PMID- 1434451 TI - [Admission and transcultural representation in an emergency service. Better understanding the differences]. PMID- 1434452 TI - [Alternative care for patients with AIDS]. PMID- 1434453 TI - [Visit to a psychiatric hospital in Haiti. Misery does not exclude noblesse]. PMID- 1434454 TI - [Contract negotiations]. PMID- 1434455 TI - [Meditation on limits as part of living: threat or challenge?]. PMID- 1434456 TI - [Setting processes in motion]. PMID- 1434457 TI - [Between normal and abnormal. Behind the horizon we find the adventure]. PMID- 1434458 TI - [Between identity and integrity. The difficult search for identity]. PMID- 1434459 TI - [Between stability and change. Does he, who persists really have to die?]. PMID- 1434460 TI - [A tool for the measurement of quality--the model of the Swiss Nursing Association. Quality can be measured]. PMID- 1434461 TI - [New rules for nursing education: advantages, misunderstandings]. PMID- 1434463 TI - [Successful cultural work in the health care system. Social marketing]. PMID- 1434462 TI - [The danger of that which is not expressed]. PMID- 1434464 TI - [Work and life of the nurse Elisabeth Kasser, the angel of Gurs]. PMID- 1434465 TI - [Training rules of the Swiss Red Cross: Baccalaureate, also for nursing!]. PMID- 1434466 TI - [Introduction of a nursing guide. One team, one nursing philosophy]. PMID- 1434467 TI - [Consequences for nursing of the economic measures in health care. How much latitude is left?]. PMID- 1434468 TI - [Evaluation of the self-care capabilities of patients and nurses]. PMID- 1434469 TI - [Industrial nurse--a beautiful task]. PMID- 1434470 TI - [Hospital trash. The ecologic hospital]. PMID- 1434471 TI - [Study on patients who await a diagnosis. A time of insecurity]. PMID- 1434472 TI - [Informing, reassuring, understanding. Role of nurses towards patients with AIDS]. PMID- 1434473 TI - [Educational experience. Meeting of a different type]. PMID- 1434474 TI - [Interview with Patricia Gentil, representing the Romand Center for Permanent Education. "Perspective, innovative". Interview by Francoise Taillens]. PMID- 1434475 TI - [Working conditions in the Canton Vaud. Unemployed nurses in spite of personnel shortage?]. PMID- 1434476 TI - [Touching during everyday care--summary of a diploma paper. In the hands of the healers]. PMID- 1434477 TI - [A mouth care concept--with special reference to the problems of cancer patients. A healthy mouth]. PMID- 1434478 TI - [Tasks in physical therapy following hand surgery]. PMID- 1434480 TI - [The aged don't drink enough]. PMID- 1434479 TI - [Alzheimer's disease: etiology, clinical aspects and therapy]. PMID- 1434481 TI - [Which interventions can be performed on an outpatient basis in pediatrics]. PMID- 1434482 TI - [Preparation of cytostatic agents in the laminar airflow]. PMID- 1434483 TI - [Technique of urethral catheterization]. PMID- 1434484 TI - [Suprapubic urinary diversion with the Freka-Cyst-Set]. PMID- 1434486 TI - [A controlled measure for the relief of the nursing service--use of ward assistants]. PMID- 1434485 TI - [The importance of an instrument specialist in an intensive care unit]. PMID- 1434487 TI - [Tasting the cherries--or "People eat the way they are". Defense mechanisms and joy of living as forms of neurose-psychological ego-instances in the mother-child interaction]. PMID- 1434488 TI - [Hospital chaplain: more help for aged psychiatric patients. Talking about emotional problems the same way as about a head cold]. PMID- 1434489 TI - [Health has been and will be an expensive idol]. PMID- 1434490 TI - [Burial. Stillbirths disposed of like hospital garbage]. PMID- 1434491 TI - Acute gastric distention in guinea pigs. PMID- 1434492 TI - Chronic spinal cord-injured cats: surgical procedures and management. PMID- 1434493 TI - Factors associated with intestinal amyloidosis in pigtailed macaques (Macaca nemestrina). AB - Factors associated with intestinal amyloidosis in pigtailed macaques (Macaca nemestrina) were studied in 74 cases at the Washington Regional Primate Research Center. The medical records of monkeys during the 5-year period from 1983 to 1988 were analyzed to determine the age at death, age at first episode of diarrhea, number of episodes of diarrhea, episode and cumulative duration of diarrhea, and etiologies of diarrhea. Univariate analysis, using one control for each case, indicated that only episode duration was related to intestinal amyloidosis. Affected monkeys had significantly longer mean episode durations of diarrhea. None of the etiologies examined--bacteria, protozoa, fungi, and simian retrovirus -were significant risk factors for amyloid deposition in the intestinal tract. PMID- 1434494 TI - Diarrhea rates and risk factors for developing chronic diarrhea in infant and juvenile rhesus monkeys. AB - Ten independent risk factors were evaluated in an effort to identify predictors of problem diarrhea at weaning and chronic diarrhea in infant and juvenile rhesus monkeys (Macaca mulatta) at the California Primate Research Center. None of the variables proved to be a significant predictor of problem diarrhea at weaning; however, two of the variables were significant predictors for developing chronic diarrhea. Odds ratios, adjusted for other variables in the logistic regression model, showed that compared with females, males were nearly three times more likely to develop chronic diarrhea, and nursery-reared animals were 7.5 times more likely to develop chronic diarrhea than were breast-fed animals. The annual incidence rates for problem diarrhea at weaning for 1978, 1979, and 1980 were 49%, 37%, and 41%, respectively. A weighted average annual incidence rate for problem diarrhea at weaning for the 3-year period was 39%. The incidence rate for chronic diarrhea for the 3-year period was 49%. PMID- 1434495 TI - Endometrial venous aneurysms in three New Zealand white rabbits. AB - Hematuria in rabbits has been associated with uterine adenocarcinoma, uterine polyps, renal infarction, urolithiasis, cystitis, bladder polyps, and pyelonephritis. Three adult female New Zealand White rabbits (Oryctolagus cuniculus) developed apparent hematuria, as suggested by blood in their excreta pans. They had been immunized with antigen-adjuvant emulsions, but had uneventful clinical histories. Physical examination disclosed no abnormalities, and laboratory tests, including hematology, serum chemistries, urinalyses, urine cultures, ultrasonography, and intravenous pyelography disclosed mild anemia, hematuria, and proteinuria in two of the rabbits. Antibiotic therapy failed to alleviate clinical signs. Two rabbits were euthanized because of persistent urogenital bleeding and the third rabbit underwent exploratory laparotomy and ovariohysterectomy. Multiple endometrial venous aneurysms were present in the uteri of all rabbits and urogenital bleeding was attributed to episodic bleeding from these lesions. Varices and aneurysms of uterine subserosal and myometrial venous plexuses, but not of endometrial vessels in women have been reported. To our knowledge, endometrial venous aneurysms have not been reported in animals previously. Our findings indicate that the differential diagnoses for sporadic apparent hematuria in female rabbits should include endometrial aneurysms. PMID- 1434496 TI - Effects of sex hormones on fulminant hepatitis in LEC rats: a model of Wilson's disease. AB - LEC rats, which have hereditary hepatitis and have recently been proposed as an animal model for Wilson's disease, were examined to determine the effects of sex hormones on fulminant hepatitis. After the rats had undergone ovariectomies or orchidectomies (castration) and were compared with intact rats, the age at the onset of fulminant hepatitis was not substantially altered but the survival rates decreased from 50% to 12.5% for females and 75% to 14.3% for males, indicating that sex hormones did not influence the occurrence of fulminant hepatitis but influenced mortality due to fulminant hepatitis. When testosterone was administered to the ovariectomized or orchidectomized rats, the survival rate increased to over 90% in both sexes. In contrast, estradiol did not affect the survival rate of either sex but affected the onset of fulminant hepatitis. That is, with the administration of estradiol, the age at which serum GPT activity reached its maximum was delayed 4 weeks in ovariectomized rats and 6 weeks in orchidectomized rats as compared with intact rats. A similar but somewhat weaker tendency appeared in rats given progesterone. The results of our study indicate that sex hormones have no effect on the rate of occurrence of hepatitis but affect the progression of hepatitis. In particular, testosterone increased the survival rate of rats with fulminant hepatitis, and exogenous estradiol delayed the onset of hepatitis for several weeks. PMID- 1434497 TI - A reproducible method for producing and quantifying the stages of fracture repair. AB - Male CD-1 mice, 4 to 6 months of age, were used to establish a reproducible model to study the stages of fracture repair. A custom-designed fracture apparatus was constructed, and trials with it demonstrated its capacity to reliably reproduce a closed fracture of the tibia. Dietary and sleep habits in the treated mice were the same as unfractured control mice. Four stages of fracture repair were documented and the duration of each stage was quantifiable and reproducible. The last stage of fracture repair was completed by 21 days postfracture. The reproducibility of the fracture, the reproducibility of the times and stages of fracture repair, the relatively short time to complete the fracture repair process, and the minimal discomfort which allowed the mice to maintain a normal daily routine, suggest that this is an ideal animal model for studying the fracture repair process. PMID- 1434498 TI - Lymphoblastic lymphoma in a colony of N:NIH(S)-bg-nu-xid mice. AB - During a 1-year period, 28 animals from a breeding colony of N:NIH(S)-bg-nu-xid mice were discovered to have rapidly enlarging subcutaneous swellings in the ventral, cervical, and axillary regions. Five of the mice also had hind limb paresis. Twenty-two of the mice were heterozygous nude females, five were homozygous nude males, and one was a homozygous nude female. All of the above mice were homo- or hemizygous for the beige and X-linked immunodeficiency mutations. The average age of the mice was 8.3 months. Generalized enlargement of the peripheral and internal lymph nodes was present at the time of necropsy examination. Other lesions commonly noted at necropsy included splenomegaly (15 mice), pale and thickened ventral lumbar spinal musculature (11 mice), and opaque, thickened meninges of the brain (10 mice). Histologic examination consistently disclosed infiltrates of neoplastic lymphoblasts in multiple tissues including lymph nodes, spleen, bone marrow, and meninges of the brain and spinal cord. The cells were positive for IgG on immunofluorescent staining, suggesting that the tumors were of B cell origin. The neoplasms observed in these mice have several similarities to tumors found in immunodeficient humans, suggesting that these mice may serve as useful animal models of lymphoma. PMID- 1434499 TI - Convulsions in senescence-accelerated mice (SAM-R/1/Eis). AB - Senescence-accelerated mice (SAM) are one of the animal models used for studying senescence, which consist of several substrains such as SAM-R/1, R/2, P/1, P/2. SAM-R/1/Eis maintained in Eisai Tsukuba Research Laboratories, Ibaraki, Japan, was originally introduced as a substrain of a normal control SAM-R/1 from Kyoto University, Japan. We have noted signs of convulsions in SAM-R/1/Eis mice during routine animal care, particularly while changing cages. We identified the clinical signs and determined the concentrations of glucose and immunoreactive insulin in plasma of SAM-R/1/Eis mice. There were no differences in the male:female ratios of mice showing prodrome only, grand mal, or no-signs. The ages at which prodrome and grand mal were first noted peaked between 20 and 25 weeks. Concentrations of glucose and immunoreactive insulin in plasma did not indicate the mice were in insulin hypoglycemia, which is one cause of convulsions. AKR strain mice, some of which originated with the SAM strain are known to become convulsive by repeated "throwing" stimulations. Conversely, in SAM-R/1/Eis, throwing stimuli are not needed to cause convulsive signs. Thus it is likely that in SAM-R/1/Eis mice the signs are triggered by repeating mild environmental changes, such as changing cages. The results of this study show that SAM-R/1/Eis is neither a normal control strain, nor an original SAM-R/1 strain. But it is possible that SAM-R/1/Eis is another useful animal model for studying spontaneous convulsion. PMID- 1434500 TI - Persistent free-running circannual reproductive cycles during prolonged exposure to a constant 12L:12D photoperiod in laboratory woodchucks (Marmota monax). AB - Serum levels of gonadal steroid were assayed at approximately 3-month intervals in groups of 5 to 8 male or female woodchucks which were exposed to a natural photoperiod for 1 year as yearlings or 3 years as adults (Study 1), or a constant photoperiod of 12L:12D from birth for 4.5 years (Study 2). After 4.5 years of 12L:12D, food intake was measured in November and compared with that in natural photoperiod animals (Study 3). Other groups of 11 males and 3 females were housed in 12L:12D for 2.5 years after capture at 2 months of age, and gonadal structure and serum steroid levels in November were compared with those of animals at selected times in the normal annual cycle (Study 4). All animals were provided food and water ad libitum and were not induced to hibernate. In Study 1, normal circannual breeding season elevations in testosterone in males and in progesterone in females were detected in most animals maintained in natural photoperiod. In Study 2, similar cycles persisted for 4.5 years in animals exposed to 12L:12D. However, based on quarterly blood samples, obvious asynchrony relative to natural light animals appeared to develop after 2, 3, or 4 years, with apparent free-running intervals of about 10 to 11 months. In Study 3, mean daily food consumption in late autumn for woodchucks in the 12L:12D group was 72% greater than animals in the natural photoperiod. In Study 4, some woodchucks exposed to 12L:12D for only 2.5 years had prematurely increased spermatogenic activity, Leydig tissue development, and elevated serum testosterone levels in November. They were similar in November to those in natural photoperiod animals in March, and significantly greater than those in natural photoperiod animals in November when normal regression and repair of the testis was complete. Likewise, females in the 12L:12D group had luteinized follicles and elevated progesterone in November which were not noted in natural photoperiod animals and which were similar to those observed during the spring in unbred females under normal conditions. The results suggest that circannual cycles of metabolic and reproductive activity in woodchucks persist in the absence of normal changes in photoperiod, are entrained to seasonal changes in the natural photoperiod, and can recede to a periodicity of less than 12 months within 2.5 to 4 years of laboratory maintenance in 12L:12D. PMID- 1434501 TI - Pickle barrels as enrichment objects for rhesus macaques. AB - Two breeding groups of rhesus monkeys (Macaca mulatta) housed in outdoor enclosures on Key Lois island were observed for 84 hours. Instantaneous scan sampling of a focal animal was used to gather data to test hypotheses concerning frequencies of agonistic and affiliative behaviors as well as differential use of pickle barrels as enrichment objects. Type of barrel used, behavior, and age/sex class of the animal were noted. Barrels were arranged three ways: unattached, on a swivel, and stationary. The behaviors of animals in an enriched environment were compared with control condition animals, which did not have pickle barrels. Animals in an enriched environment accounted for 60.8% (n = 56) of total affiliative contact, 62.2% (n = 399) of total social grooming, and 26% (n = 5) of total agonistic noncontact. A total of 134 scans of barrel use were observed. Analyses of the data showed that swivel and stationary barrels were used the most (55% of all scans of barrel use). Yearlings, juvenile females, and old males used barrels most often (82.8% of all scans of barrel use), although they constituted only 39% of the enriched environment population. In this study, pickle barrels provided enrichment for young and old animals of both sexes. PMID- 1434502 TI - Ultrasound-guided blood sampling of rabbit fetuses. AB - A rabbit animal model for hemolytic disease of the newborn has been previously described. However, evaluating the effects of this disease was limited to histologic and hematologic examinations of liveborn kitlings. To assess the feasibility of in utero blood sampling, we performed ultrasound-guided cardiac sampling of 50 fetuses in 16 New Zealand White does on days 26 and 27 of gestation. The overall rate of successful sampling was 80%. The procedure-related mortality declined to 35% by the third phase of the study. The mean (+/- SD) hematocrit (%) and reticulocyte values (#/100 RBCs) on day 26 were 26.3 +/- 3.3 and 35.6 +/- 5.1, respectively; values on day 27 were 31.3 +/- 4.9 and 27.5 +/- 7.6. The results of this study suggest that hematologic data can be obtained from rabbit fetuses in the majority of cases with only moderate fetal loss. PMID- 1434503 TI - Evaluation of subcutaneous chambers as an alternative to conventional methods of antibody production in chickens. AB - We compared antibody levels among serum, egg yolk extract, and granuloma fluid in chickens immunized with bovine serum albumin (BSA). One group of hens was immunized by intramuscular and subcutaneous injection of bovine serum albumin in complete Freund's adjuvant, followed by two subsequent booster injections in incomplete Freund's adjuvant. Two other groups were surgically implanted with plastic, perforated wiffle balls (subcutaneous chambers). After a 30-day recovery period, one of the groups with subcutaneous chambers was immunized with BSA in sterile water with two subsequent boosts. The other group was injected with only sterile water. Serum samples, eggs, and granuloma fluid were collected biweekly and analyzed to determine specific IgG, total IgG, and total protein. The subcutaneous chambers were well tolerated. Quantitative ELISAs of serum, egg yolk extract, and granuloma fluid specimens disclosed that specific antibody levels were present in all specimens by 2 weeks after primary immunization. During the course of the experiment, specific antibody levels of serum and egg yolk specimens were significantly higher than those of granuloma fluid (P less than 0.05). However, an additional injection of antigen into the subcutaneous chambers resulted in specific antibody levels in granuloma fluid specimens that were comparable to those of serum and egg yolk extract. Use of subcutaneous chambers in chickens may be a viable alternative to routine antibody production methods. PMID- 1434504 TI - Diagnostic exercise: cardiomegaly in a young dog. PMID- 1434505 TI - Congenital hypotrichosis in a rhesus monkey. PMID- 1434506 TI - Eradication of pinworms (Syphacia obvelata) from Syrian hamsters in quarantine. PMID- 1434507 TI - An occipito-temporal syndrome in adolescents with optimally controlled hyperphenylalaninaemia. AB - The study included 16 adolescents with optimally controlled hyperphenylalaninaemia (McKusick 26160), of whom six did not require treatment according to conventional criteria. All except the two patients with lowest median serum phenylalanine level throughout childhood (most values at 200-300 mumol/L) had white matter abnormalities detectable with magnetic resonance imaging. The lesions were particularly prominent in the watershed regions between the posterior and middle cerebral arteries. In most patients with moderate or severe hyperphenylalaninaemia frontal white matter lesions were present as well. Normal proton magnetic resonance spectra indicated that the lesions were stable. Occipital EEG abnormalities were frequent, and deficient performance on a pattern recognition test was a characteristic neuropsychological finding. Serum phenylalanine levels at about 300 mumol/L or below throughout childhood and early adolescence may be required to avoid lesions. The present study demonstrates the limitations of even an optimally controlled dietary regimen in hyperphenylalaninaemia. PMID- 1434508 TI - Allopurinol challenge test in children. AB - The allopurinol challenge test was performed on 44 healthy subjects (28 children and 16 adolescents) in order to establish normal values of urinary orotic acid excretion following allopurinol ingestion in the paediatric population. The subjects were divided into three groups according to their age: 6 months to 6 years; 6 years to 10 years; and 10 years to 17 years. They were given 100 mg, 200 mg, or 300 mg of allopurinol, respectively (based on age) in a single oral dose. Maximum peak urinary orotic acid levels following ingestion of allopurinol were 13.0 (n = 14), 9.3 (n = 14), and 10.2 (n = 16) mumol/mmol creatinine in the three groups, respectively. In all children tested the peak orotic acid level was 3.1 +/- 2.7 mumol/mmol creatinine (mean +/- SD, n = 44). This allopurinol challenge test was also performed in six children with urea-cycle disorders, including five females with ornithine transcarbamylase (OTC) deficiency, all of whom demonstrated abnormally elevated levels of urinary orotic acid (peak levels of 26 134 mumol/mmol creatinine) following allopurinol ingestion. PMID- 1434509 TI - Prenatal diagnosis of non-ketotic hyperglycinaemia. AB - Non-ketotic hyperglycinaemia (NKH) is a devastating neurological disease for which there is no effective therapy. Consequently, most couples with a pregnancy known to be at risk for NKH request prenatal diagnosis. We have applied the combination of chorionic villus (CVS) assay for glycine cleavage enzyme activity and determination of amniotic fluid glycine concentration to increase the reliability of prenatal diagnosis for this disorder beyond that of each of these methods alone. All 15 of the at-risk pregnancies monitored had CVS glycine cleavage assay and five also had amniotic fluid glycine measurements. Two cases had no detectable cleavage activity in CVS and one gave uninterpretable enzyme results. Amniotic fluid glycine concentration was increased in all three and NKH was confirmed by abortus tissue assays for cleavage activity and amino acids. The remaining 12 case had activity in CVS (two also had normal amniotic fluid glycine levels) and delivered unaffected infants. Four of these 12 cases had cleavage activities below or at the low end of the normal range, perhaps indicating carrier status. We believe that the combination of CVS glycine cleavage assay and amniotic fluid glycine measurement is currently the best approach to the prenatal diagnosis of NKH. PMID- 1434510 TI - Fructose and glucagon loading in siblings with fructose-1,6-diphosphatase deficiency in fed state. AB - Hypoglycaemia induced by fructose administration is one of the diagnostic clues to fructose-1,6-diphosphatase (FDPase) deficiency (McKusick 229700). However, the pathological mechanism of this reactive hypoglycaemia is not fully known. This paper describes two siblings with FDPase deficiency, diagnosed enzymatically in leukocytes, who failed to correct reactive hypoglycaemia after glucagon administration even in the fed state, supporting a possibility that disturbed hepatic phosphorylase activity may be a main cause of reactive hypoglycaemia. PMID- 1434511 TI - In vivo 13C-NMR evaluation of glycogen content in a patient with glycogen storage disease. AB - Glycogen storage disease was suspected in a 10-month-old boy. Initial technical problems did not permit the determination of the precise enzyme, deficiency, and type VI glycogen storage disease was only diagnosed at the age of 2 years. In the mean time, natural abundance 13C nuclear magnetic resonance evaluation of muscular and hepatic glycogen content indicated normal muscular glycogen and increased hepatic glycogen in our patient, a finding which strongly argued for the diagnosis of type VI glycogen storage disease. Even though the use of nuclear magnetic resonance might seem, in this situation, a somewhat circuitous means of reaching the diagnosis, it appears that nuclear magnetic resonance could provide a useful tool for a non-invasive diagnosis of glycogen storage diseases. PMID- 1434512 TI - Measurement of acyl-CoA dehydrogenase activity in cultured skin fibroblasts and blood platelets. AB - The measurement of acyl-CoA dehydrogenase activity is an essential part of the investigation of patients with suspected defects of fatty acid oxidation, and recently the organometallic oxidant ferricenium hexafluorophosphate has been introduced as an electron acceptor for these assays. However, we show that when medium-chain acyl-CoA dehydrogenase activity was measured in cultured skin fibroblasts and platelets from patients with proven defects of this enzyme, there was considerable residual enzyme activity when this electron acceptor was used. The ferricenium assay is not as specific as the anaerobic ETF-linked assay in the biochemical diagnosis of medium-chain acyl-CoA dehydrogenase deficiency in fibroblasts, and therefore is of limited clinical applicability in its present form. PMID- 1434513 TI - Carrier detection in glutaric aciduria type I using interleukin-2-dependent cultured lymphocytes. AB - Cultured interleukin 2 (IL-2)-dependent leukocytes from 13 patients with glutaric aciduria type I, 12 obligate carriers, 105 family members and 31 normal controls were assayed for glutaryl-CoA dehydrogenase activity. Of the 13 affected patients, 10 (all Ojibway Indian) had residual enzyme activity (2-13% of control) and 3 patients (all non-Indian) had undetectable enzyme activity. There was partial overlap between the distribution of enzyme activity in obligate heterozygotes and in normal controls (mean values +/- SD: 6.29 +/- 0.94 and 10.75 +/- 2.58 nmol/h per mg protein respectively). Using an arbitrary cutoff level of < 7 nmol/h per mg protein as presumptive evidence of carrier status, the observed frequency of carriers did not differ significantly from that expected from their a priori risk of carrier status. Thirteen per cent of the family members had inconclusive status (activity between 7 and 8.5 nmol/h per mg protein). The method appears suitable for carrier detection, although definitive carrier assignment awaits identification of the mutation(s) responsible for glutaric aciduria type I. PMID- 1434515 TI - N-acetylglucosamine 6-sulphatase deficiency in a Nubian goat: a model of Sanfilippo syndrome type D (mucopolysaccharidosis IIID). AB - A male Nubian goat (SD-1) presented at birth with neurological manifestations consistent with a lysosomal storage disease. Histological studies of tissue obtained at autopsy suggested glycosaminoglycan storage. Total urinary glycosaminoglycan levels, as measured by the uronic acid method, were elevated but overlapped with levels in a younger control goat. However, N-sulphate content was increased 2- to 5-fold, suggestive of heparan sulphate excretion, and this elevation was confirmed by cellulose acetate electrophoresis. Further, urinary levels of free N-acetylglucosamine 6-sulphate were increased 6-fold over controls, SD-1 cultured skin fibroblasts, labelled with [35S]sulphate from the incorporated twice as much radioactivity into macromolecular material as did normal fibroblasts. Forty-eight hours after removal of [35S]sulphate from the medium the SD-1 fibroblasts retained 58% of the label, whereas in control fibroblasts it had declined to 20%, indicative of [35S]proteoglycan storage in SD 1. The assay of fibroblast extracts revealed a profound deficiency of N acetylglucosamine 6-sulphatase whereas eight other activities including beta mannosidase, arylsulphatase B, iduronate 2-sulphatase, N-acetylgalactosamine 6 sulphatase, and heparin sulphamidase were normal. Mixing of SD-1 sonicates with normal sonicates showed no evidence of an inhibitor, and mixing of SD-1 sonicates with Sanfilippo D cell sonicates yielded no activity. These data ruled out multiple sulphatase deficiency and suggested the first example of the human Sanfilippo syndrome, type D (N-acetylglucosamine 6-sulphatase deficiency) in goats. PMID- 1434514 TI - Characterization of phosphofructokinase-deficient canine erythrocytes. AB - Dogs homozygously affected with muscle-type phosphofructokinase (PFK) deficiency had about 20% of normal erythrocyte PFK activity and exhibited a compensated haemolytic anaemia. Erythrocyte glucose-6-phosphate and fructose-6-phosphate concentrations were increased and dihydroxyacetone phosphate and 2,3 bisphosphoglycerate values were below normal in affected dogs. Other intermediates distal to the PFK step were not significantly below normal and fructose-1,6-bisphosphate was even above normal. Erythrocyte ATP was higher than normal in affected dogs owing to the reticulocytes present. Abnormal adenylate metabolism was demonstrated by low ATP/AMP and ADP/AMP ratios and the inability to maintain ATP content when affected erythrocytes were incubated with cyanide. Glucose-1,6-bisphosphate content was normal, and fructose-2,6-bisphosphate content in affected canine erythrocytes was higher than normal. Studies of erythrocyte PFK isozymes revealed altered enzyme kinetic properties in affected dogs which appeared to be due to the loss of the M-type subunit. PMID- 1434516 TI - Serum selenium levels in individuals on PKU diets. AB - Serum selenium levels in 73 patients with phenylketonuria were significantly lower than in controls. The phenylketonuric and hyperphenylalaninaemic individuals taking the non-supplemented amino acid mixture generally had lower levels: 36% were below the normal range as defined by our laboratory, compared with 19% in the supplemented group. The low levels were present even in those on diet, who had a greater phenylalanine tolerance--that is, a tolerance for more than 9 x 50 mg phenylalanine exchanges per day, in other words a higher intake of natural protein. Individuals on long-term synthetic diets may be at risk for selenium deficiency even on selenium supplements. In areas where the soil may be low in selenium, the deficiency may be aggravated. Long-term low levels may impair health but the required amount of selenium supplementation remains uncertain. PMID- 1434518 TI - Lesch-Nyhan syndrome in a girl. PMID- 1434517 TI - Elevated plasma carnitine in the hepatic form of carnitine palmitoyltransferase-1 deficiency. AB - In a boy with a defect in fatty acid oxidation due to the hepatic form of carnitine palmitoyltransferase-1 deficiency, plasma carnitine concentrations were found to be twice normal. The elevation in plasma carnitine levels was accompanied by an unusually high renal threshold for free carnitine, suggesting a secondary increase in carnitine transport. Similar to other fatty acid oxidation disorders involving the carnitine cycle, urinary dicarboxylic acids were not abnormally elevated during illnesses. The combination of elevated plasma carnitine levels and absence of dicarboxylic aciduria may help to distinguish the hepatic form of carnitine palmitoyltransferase-1 deficiency from other defects in fatty acid oxidation. PMID- 1434519 TI - Simultaneous detection of mutant gene and transgene in ornithine carbamoyl transferase-deficient spf-ash mice with rat OCT gene. PMID- 1434520 TI - Defects of mitochondrial respiratory enzymes in cloned cells from MELAS fibroblasts. PMID- 1434521 TI - The mutant mitochondrial genes in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) were selectively amplified through generations. PMID- 1434522 TI - Multiple enzyme defects in mitochondria of a case with congenital lactic acidosis and hyperammonaemia. PMID- 1434523 TI - Study of bone marrow transplantation for Niemann-Pick mice using Sry and Zfy genes. PMID- 1434524 TI - Molecular diagnosis of maple syrup urine disease: screening and identification of gene mutations in the branched-chain alpha-ketoacid dehydrogenase multienzyme complex. PMID- 1434525 TI - Liver regeneration and growth factors: old puzzles and new perspectives. PMID- 1434526 TI - Hyperglycemia and microangiopathy. Direct regulation by glucose of microvascular cells. PMID- 1434527 TI - Topographic dissociation between mitochondrial dysfunction and cell death during low-flow hypoxia in perfused rat liver. AB - BACKGROUND: Although it has been postulated that mitochondrial dysfunction and oxygen radicals may play a role in the mechanisms of hypoxic liver injury, little is known about the intralobular topographic relationship between a disorder in oxygen metabolism and cell death during hypoxia. EXPERIMENTAL DESIGN: Intralobular heterogeneity of mitochondrial dysfunction and its topographic relationship to cell death during 25% low-flow hypoxia was visually demonstrated in perfused rat hepatic microcirculatory units by dual-color digital microfluorography using rhodamine 123, a fluorochrome sensitive to the mitochondrial membrane potential, and propidium iodide, which labels the nuclei of nonviable cells with a concomitant enhancement of fluorescence. RESULTS: In the normoperfused liver from fasted rats, no significant depletion of the mitochondrial membrane potential values was observed in any portion of lobules during 100 minutes. In the liver treated with the 40-minute hypoxia, the mitochondrial membrane potential values within the entire lobule were significantly decreased. After a longer period of hypoxia, the pericentral fluorescence decreased to background levels, and the intralobular gradient showed a steep decline midway between the periportal and pericentral regions. Cell death was at first prominent in the midzone at 40 minutes, and then extended towards the pericentral regions, forming centrilobular necrosis at 100 minutes. Although allopurinol diminished the early midzonal cell death and retarded the development of centrilobular necrosis, it did not attenuate depression of the mitochondrial membrane potential. CONCLUSIONS: It is conceivable that mitochondrial dysfunction per se may not be related to the intralobular distribution of cell death during hypoxia. On the other hand, mitochondrial dysfunction in the centrilobular regions seems to be an important event leading to early midzonal oxidative tissue damage in that this change may involve ATP breakdown and the subsequent enhancement of xanthine oxidase-mediated oxidative cell injury in the midzonal regions, which are incompletely oxygenated. PMID- 1434528 TI - Regulation of p26-bcl-2 protein levels in human peripheral blood lymphocytes. AB - BACKGROUND: The protein encoded by the bcl-2 (B cell lymphoma/leukemia-2) proto oncogene has been implicated in the regulation of lymphocyte cell survival and has been shown to interfere with programmed cell death (apoptosis). Recently, controversy has emerged regarding the expression of bcl-2 in circulating peripheral blood lymphocytes (PBL) and its correlation with lymphocyte proliferation. Using immunohistochemical methods, Pezzella et al. (Pezzella F, Tse G, Cordell J, Pulford K, Gatter K, Mason D. Am J Pathol 1990; 137:225-32) detected abundant amounts of Bcl-2 protein in resting PBLs and observed an inverse correlation between bcl-2 expression and cellular proliferation in lymphoid tissues. In contrast, previous in vitro studies of bcl-2 mRNAs showed that expression of this gene is very low in unstimulated PBLs but can be markedly induced when lymphocytes are stimulated to proliferate in culture (Reed JC, Tsujimoto Y, Alpers JD, Croce CM, Nowell PC. Science 1987; 236:1295-9; Granniger W, Seto M, Boutain B, Goldman P, Korsmeyer S. J Clin Invest 1987; 80:1512-5). EXPERIMENTAL DESIGN: To resolve this issue, the regulation of p26-Bcl-2 protein levels was examined in freshly isolated and in cultured human PBLs by immunoblotting using two different polyclonal antisera specific for the human Bcl 2 protein. RESULTS: When freshly isolated from whole blood, resting PBLs contained easily detectable amounts of p26-Bcl-2 protein that did not significantly change in culture when cellular proliferation was stimulated with mitogenic lectins and lymphokines. If processing of the blood was delayed, however, p26-Bcl-2 protein was low or undetectable in resting PBLs and underwent marked increases in its relative levels after in vitro stimulation of PBLs by mitogenic lectins and lymphokines. CONCLUSIONS: The findings indicate that bcl-2 is normally expressed in quiescent circulating lymphocytes, consistent with a role for this gene in the maintenance of lymphocyte survival, and illustrate the importance of correlating in vitro and in vivo expression data. PMID- 1434529 TI - Chinese hamster ovarian cells transfected with human parathyroid hormone-related protein cDNA cause hypercalcemia in nude mice. AB - BACKGROUND: Parathyroid hormone-related protein (PTH-rP) has been implicated as a causative factor in the humoral hypercalcemia of malignancy. Animal models of hypercalcemia of malignancy that have traditionally utilized human or animal tumors or injections or infusions of hypercalcemic factors have limitations that may prevent exact delineation of the biologic effects of tumor-produced PTH-rP. EXPERIMENTAL DESIGN: To assess the effects of tumor-produced PTH-rP in vivo, we have transfected Chinese hamster ovarian (CHO) cells with cDNA encoding human preproPTH-rP-(1-141) which then stably express only PTH-rP. We inoculated these tumor cells into nude mice, and compared tumor-bearing nude mice with similar tumor-bearing nude mice inoculated with non-transfected CHO cells using standard parameters of calcium homeostasis. RESULTS: The nude mice carrying tumors expressing PTH-rP became hypercalcemic over 12 to 18 days. Blood ionized calcium values correlated positively with plasma PTH-rP concentration and tumor volume. Plasma PTH-rP concentrations in hypercalcemic mice were similar to those reported in humans with hypercalcemia of malignancy. Bone histology and histomorphometry from hypercalcemic nude mice demonstrated increased bone resorption when compared with mice bearing nontransfected CHO tumors. CONCLUSIONS: We have produced an animal model of tumor-produced PTH-rP by transfecting CHO cells with the cDNA for PTH-rP and inoculating these tumor cells into nude mice. Hypercalcemia in this model is mediated in part by the effects of PTH-rP to increase osteoclastic bone resorption. The model is advantageous because PTH-rP alone is secreted in a prolonged, constitutive fashion with pharmacokinetics similar to naturally occurring tumors. It should prove to be a useful model to study the effects of tumor-produced PTH-rP in vivo. PMID- 1434530 TI - Carbohydrate metabolism in human renal clear cell carcinomas. AB - BACKGROUND: Renal cell carcinomas can be subclassified into clear cell carcinomas, chromophobe cell carcinomas, chromophilic cell carcinomas, and oncocytomas. Previous studies, in which no distinction among the different types of renal cell tumors and their grades of malignancy was performed, showed that these tumors had high glycolytic rates. EXPERIMENTAL DESIGN: The carbohydrate metabolism of control human kidney samples and renal clear cell carcinomas with different degrees of cytologic malignancy (G I, G II, and G III) was studied by determining the glycogen and glucose-6-phosphate levels and the activities of key enzymes involved in glycolysis (hexokinase, glucokinase, pyruvate kinase), gluconeogenesis (glucose-6-phosphatase, fructose-1,6-diphosphatase), and the pentose phosphate pathway (glucose-6-phosphate dehydrogenase) in these tissues and compared with those of a limited number of chromophilic cell carcinomas, chromophobe cell carcinomas, and oncocytomas. RESULTS: The glycogen and glucose-6 phosphate levels were significantly higher in G I, G II, and G III clear cut carcinomas than in control kidneys; glucokinase, hexokinase, and glucose-6 phosphate dehydrogenase activities remained unchanged, pyruvate kinase activity was enhanced, and glucose-6-phosphatase as well as fructose-1,6-diphosphatase activities were strongly reduced when compared with control kidney values. In chromophilic cell carcinomas glycogen content, glucose-6-phosphate dehydrogenase, and pyruvate kinase activities were elevated, while fructose-1,6-diphosphatase activity was reduced. In chromophobe cell carcinomas glycogen content was elevated and gluconeogenesis was reduced, whereas glycolysis was not activated. In oncocytomas glycogen was not detected and glucose-6-phosphate dehydrogenase, pyruvate kinase, and fructose-1,6-diphosphatase activities remained unchanged. CONCLUSIONS: It has been demonstrated that a series of characteristic changes occur in the carbohydrate metabolism of renal clear cell carcinomas: glycogen and glucose-6-phosphate levels increase, glycolysis is activated, and gluconeogenesis is reduced. Furthermore, the alterations of the carbohydrate metabolism within clear cell carcinomas are clearly distinct from those observed in chromophilic cell carcinomas, chromophobe cell carcinomas, and oncocytomas. PMID- 1434531 TI - Platelet-derived growth factor receptor-beta is induced during tumor development and upregulated during tumor progression in endothelial cells in human gliomas. AB - BACKGROUND: Endothelial cells proliferate during brain development, are quiescent in normal adult brain but proliferate again under pathologic conditions such as glioma growth. The vascular phenotype of low grade glioma is comparable to normal brain, however high grade gliomas are focally highly vascularized and there is associated prominent endothelial cell proliferation. The mechanisms of this change in vascular phenotype are unknown but there is evidence that growth factors play an important role in this process as well as in normal angiogenesis and vascular differentiation. EXPERIMENTAL DESIGN: To investigate whether endothelial cells become activated during tumorigenesis and progression of human gliomas by a platelet-derived growth factor (PDGF) dependent pathway, we analyzed platelet-derived growth factor receptor-beta (PDGFR-beta) expression by in situ hybridization and immunocytochemistry in normal human brain, astrocytoma (grade II), anaplastic oligo-astrocytoma (grade III), and glioblastoma multiforme (grade IV). RESULTS: PDGFR-beta mRNA was not detectable in the vessels of normal human brain, but was expressed in the vasculature of low and high grade gliomas, particularly in endothelial cell proliferations in glioblastomas. The expression of the receptor in the tumor microvessels, was confirmed by double immunofluorescence in which the staining appeared to be in the endothelial cells. Primary cultures of endothelial cells derived from glioblastoma multiforme maintained receptor expression for 2 days in vitro, whereas it was not detectable in vitro in endothelial cells derived from normal brain. Tumor cells in all grades of glioma expressed very little PDGFR-beta mRNA in situ. CONCLUSIONS: Our results indicate that the malignant phenotype in human glial tumors is associated with an upregulation of the PDGFR-beta on endothelial cells of vessels which vascularize the tumor. These findings may contribute to our understanding of the mechanisms that regulate vessel growth and differentiation in normal and pathologic states. PMID- 1434532 TI - Diverse role of pulmonary cytochrome P-450 monooxygenase. PMID- 1434533 TI - Prostate cancer: therapeutic, diagnostic, and basic studies. PMID- 1434534 TI - Relationship of cytochrome P-450 activity to Clara cell cytotoxicity. III. Morphometric comparison of changes in the epithelial populations of terminal bronchioles and lobar bronchi in mice, hamsters, and rats after parenteral administration of naphthalene. AB - BACKGROUND: The purpose of this study was to define, in quantitative terms, epithelial alterations produced by the cytochrome P-450-activated Clara cell cytotoxicant, naphthalene, in lobar bronchi and terminal bronchioles of three species with differing sensitivity: mouse, rat, and hamster. EXPERIMENTAL DESIGN: Adult mice, hamsters, and rats were treated intraperitoneally with a single dose of naphthalene ranging from 0 mg/kg up to the approximate LD50. The animals were killed 24 hours postinjection and the changes in airway epithelium characterized by light microscopic morphometry. RESULTS: In mouse, bronchiolar epithelial thickness was significantly elevated by low, but not high, doses; ciliated cell number increased and Clara cell number decreased in a dose-dependent fashion. Vacuolated Clara cell number increased in all treated mice. In rat and hamster, bronchiolar epithelial thickness or cell number did not change. In mice, bronchial epithelial thickness was unchanged except at high doses, but both ciliated and Clara cell number was decreased. In bronchi of rats, epithelial thickness and numbers of nonciliated, ciliated, and basal cells were unchanged. In bronchi of hamsters, both ciliated and nonciliated cell number were decreased. CONCLUSIONS: (a) In mice, naphthalene-induced acute bronchiolar toxicity involves not only Clara cells, but also affects the purported nontarget cell type (ciliated cells). (b) In rats and hamsters, bronchiolar epithelium is insensitive to naphthalene injury. (c) In mice, injury to bronchi occurs at higher doses than in bronchioles and involves both ciliated and nonciliated cells. (d) In rats, bronchi are insensitive. (e) In hamsters, bronchi are more sensitive than bronchioles. This study emphasizes the variability of response by species, airway and epithelial cell type to cytochrome P-450-mediated pulmonary toxicants and the need for precise quantitative methods of defining both cytotoxic and metabolic events. PMID- 1434535 TI - Thrombospondin induces glomerular mesangial cell adhesion and migration. AB - BACKGROUND: Extracellular matrix components are known to modulate mesangial cell functions as adhesion, motility and proliferation. Among other extracellular matrix components, mesangial cells have been recently described to secrete thrombospondin (TSP), a high molecular weight glycoprotein, produced by several cell types, and known to play a role in embryogenesis, wound healing, angiogenesis, and tumorigenesis. The aim of this work was the functional and molecular characterization of TSP interactions with mesangial cells. EXPERIMENTAL DESIGN: Adhesion of mesangial cells to TSP-coated plastic, and chemotaxis in the Boyden chamber assay were tested. In order to identify TSP active domains, heparin, known to bind to the amino-terminal region of TSP, four monoclonal antibodies directed against specific domains of the molecule, and TSP fragments obtained by enzymatic digestion were used. RESULTS: We found that TSP induces mesangial cell adhesion and chemotaxis, in a dose dependent manner. Adhesion was inhibited by antiserum against TSP, and by an anti-CD36 monoclonal antibody tested in the presence of heparin, but not by the peptide Gly-Arg-Gly-Asp-Ser. We have also found that only the carboxy-terminal end of TSP retains the adhesive properties of the molecule, while all the fragments tested showed some degree of chemotactic activity. CONCLUSIONS: We conclude that TSP modulates mesangial cell adhesion and motility, thus acting as a potential autocrine and paracrine regulator of mesangial cell functions in normal and pathologic conditions. PMID- 1434536 TI - Pathophysiologic implications of proteinuria in a rat model of progressive glomerular injury. AB - BACKGROUND: Males of a substrain of Munich-Wistar rats (MWF/Ztm), selected for their large number of superficial glomeruli, develop spontaneous proteinuria with age, whereas females of this strain have a normal urinary protein excretion rate. EXPERIMENTAL DESIGN: We investigated the relationship between functional and structural glomerular alterations in four groups of male and female MWF/Ztm rats, respectively at 20 and 35 weeks of age. Systolic blood pressure, urinary protein excretion and composition of urinary proteins were periodically measured during the study. At the end of the observation period, renal function was evaluated with solute clearance technique and kidney tissue processed for morphologic and morphometrical analysis using light and electron microscopy. RESULTS: Systolic blood pressure in males was significantly higher than in females, and progressed toward systemic hypertension with age. Urinary protein excretion became spontaneously abnormal in males. About 50% of urinary proteins consisted of albumin, whereas 35% was a sex-dependent low molecular weight protein. Albumin excretion increased with age in these animals, whereas excretion of the sex dependent protein decreased. Urinary protein excretion in females was significantly lower than in males of the same age, remaining near normal levels. No decline in renal function with age was observed in all animal groups. Glomerular structural alterations developed progressively with age in males, leading to important glomerular and tubular alterations. Female rats maintained almost intact glomerular morphology until the end of the study. Morphometric analysis showed an important increase in glomerular volume with age in males but not in females. This glomerular tuft enlargement was the result of an increase in the number of glomerular cells and a concomitant increase in cell volume. CONCLUSIONS: Male MWF/Ztm rats develop spontaneously systemic hypertension, proteinuria of glomerular origin, and glomerulosclerosis. Female rats develop less severe hypertension and are protected from proteinuria and glomerulosclerosis. PMID- 1434537 TI - A molecular biologic study of extracellular matrix components during the development of glomerulosclerosis in murine chronic graft-versus-host disease. AB - BACKGROUND: We studied the development of glomerulosclerosis in murine chronic graft-versus-host disease, a model for human systemic lupus erythematosus. EXPERIMENTAL DESIGN: The disease was induced in (C57BL10 x DBA/2)F1 hybrids by injection of DBA/2 lymphocytes leading to deposition of auto-antibodies in the glomeruli, and a lupus type of nephritis morphologically. We have determined the levels of mRNA coding for laminin (B1 and B2), a 67 kilodalton laminin binding protein, and types I and IV collagen, in control and graft-versus host disease mice at various times after disease induction. RESULTS: Laminin and collagen mRNAs were increased in whole kidneys 4 weeks after induction of the disease. At week 10, all animals displayed dramatic stimulation of alpha 1(I), alpha 1(IV), laminin B1, and B2 mRNAs. The 67 kilodalton laminin binding protein mRNA was also doubled from week 4 to 16. In isolated glomeruli, the mRNA level coding for laminin B2 was already significantly increased from week 8. This enhancement of laminin synthesis corresponds to the mesangial expansion and to the development of laminin-containing spike formations of the glomerular basement membrane at week 8. CONCLUSIONS: The expansion of the mesangial matrix in murine chronic graft-versus-host disease is caused at least in part, by an increased production of extracellular matrix components by glomerular cells. These results demonstrate that the increase of specific extracellular matrix components mRNAs precedes light microscopic changes. Quantitative evaluation of the mRNA levels coding for extracellular matrix proteins may reveal a useful method for the early detection of the development of glomerular sclerosis at the stage preceding the onset of anatomo-clinical changes. PMID- 1434538 TI - A comparative analysis of glycosaminoglycans from human umbilical arteries in normal subjects and in pathological conditions affecting pregnancy. AB - BACKGROUND: Vascular cells express different phenotypes in adult and fetal vessels, and the extracellular matrix they synthesize should reflect these differences. Alterations of vascular proteoglycan/glycosaminoglycan is verified in disorders such as hypertension and diabetes, and when occurring during pregnancy, they bring about structural changes to fetal vessels that often lead to impaired fetus growth. Yet there is little data about the extracellular matrix of an important human fetal vessel, the umbilical artery. EXPERIMENTAL DESIGN: This study involved the biochemical characterization of the extracellular matrix of normal umbilical arteries, umbilical arteries from complicated pregnancies (maternal hypertension and diabetes and intrauterine growth retardation syndrome), and, for purpose of comparison, normal adult arteries (aorta and iliac and pulmonary arteries). Although the collagen types I:III ratio was determined in some cases, emphasis was placed on analysis of glycosaminoglycans. RESULTS: Normal umbilical arteries differ from normal adult arteries in that they contain greater concentrations of hyaluronic acid and lesser concentrations of heparan sulfate and chondroitin 4- and 6-sulfate. The umbilical artery also differs from adult arteries in the disaccharide composition of its chondroitin and heparan sulfates and in the molecular weight of this latter glycosaminoglycan. The glycosaminoglycan distribution in umbilical arteries derived from complicated pregnancies is roughly similar to that of controls. However, total glycosaminoglycan and collagen were significantly reduced, and the collagen I:III ratio was increased in the umbilical arteries from hypertension-complicated pregnancies. CONCLUSIONS: The glycosaminoglycan composition of the normal umbilical artery, a fully differentiated tissue, differs in many aspects from that of normal adult arteries. Of the cases of complicated pregnancies studied, the extracellular matrix of umbilical arteries was altered only in maternal hypertension. The changes, notably a mild fibrosis, were not very pronounced and should not impair hemodynamic properties of the vessel. PMID- 1434539 TI - Thrombin enhancement of interleukin-1 and tumor necrosis factor-alpha induced polymorphonuclear leukocyte migration. AB - BACKGROUND: Cytokines such as IL-1 alpha and tumor necrosis factor-alpha (TNF alpha) activate vascular endothelium to express leukocyte adhesion molecules that promote polymorphonuclear leukocyte (PMNL) migration and to synthesize tissue factor, thus making the endothelium a procoagulant surface. alpha-Thrombin, generated during coagulation, also activates endothelial cells. Since all these processes are likely involved in inflammation, the effect of alpha-thrombin on PMNL interaction with cytokine activated endothelium was investigated. EXPERIMENTAL DESIGN: Human umbilical vein endothelium was grown on polycarbonate filters to investigate the effects interleukin-1 alpha (IL-1 alpha), TNF-alpha, and alpha-thrombin on PMNL transendothelial migration quantitated with 51Cr labeled PMNL, and on endothelial monolayer permeability, quantitated with 125I labeled albumin (HSA). To evaluate the expression of endothelial-leukocyte adhesion molecules, enzyme-linked immunosorbent assay was performed on human umbilical vein endothelium monolayers. The effect of thrombin on PMNL accumulation and plasma exudation in inflammation was studied in a rabbit dermal model, using 51Cr-labeled blood leukocytes and [125I]HSA respectively. RESULTS: On resting human umbilical vein endothelium, alpha-thrombin induced a transient increase (2.5- to 4-fold) in monolayer permeability lasting 30 minutes. Slight but significant transendothelial migration of 51Cr-labeled PMNL was induced by alpha-thrombin (7.4 +/- 0.6% of cells added, unstimulated = 1.9 +/- 0.4%), although this response was less than that induced by f-norLeu-Leu-Phe (17%), IL-1 alpha (29%) or TNF-alpha (21%). alpha-Thrombin enhanced the initial rate of IL-1, TNF-alpha and f-norLeu-Leu-Phe induced PMNL transendothelial migration in an additive or supradditive manner (e.g., with IL-1 alpha+alpha-thrombin, migration was 58% greater than additive at 15 to 30 minutes, p < 0.001). Catalytically inactivated alpha-thrombin, D-phenylalanyl-L-propyl-L-arginine chloromethyl ketone and diisopropyl-fluorophosphate alpha-thrombin, did not enhance migration or permeability. In dermal inflammation in rabbits, alpha-thrombin (10 units/site) induced an increase in plasma protein exudation, with only a mild infiltration of PMNL. However, alpha-thrombin synergistically enhanced the PMNL infiltration induced by IL-1 alpha, TNF-alpha, but not that induced by zymosan activated plasma (C5a) or IL-8 (neutrophil-activating peptide-1). These measurements were confirmed histologically. Investigations into the mechanisms of the enhancement of PMNL migration indicated that individually vascular permeability changes, prostaglandins, platelet activating factor, and P-selectin expression did not account for the observation effects. CONCLUSIONS: Alpha thrombin may have a role in synergistically enhancing PMNL infiltration at sites of inflammation, in part via enzymatic action on the cytokine activated endothelium. The mechanisms involved in this effect are likely a complex interaction. PMID- 1434540 TI - Langerhans cells, macrophages and lymphocyte subsets in the cervix and vagina of rhesus macaques. AB - BACKGROUND: The lower reproductive tract is an important site of contact with pathogenic microorganisms and local immune responses to a variety of antigens have been reported. The purpose of this investigation was to define the morphology of the mucosa-associated lymphoid tissue in the genital tract of rhesus monkeys. EXPERIMENTAL DESIGN: Monoclonal antibodies were used in an immunoperoxidase staining technique to identify immunophenotypic markers on mononuclear cells in the vaginal and cervical mucosa of 14 cycling, multiparous rhesus macaques. RESULTS: CD1a+ Langerhans cells were present in the stratified squamous epithelium of the vagina (14 animals) and ectocervix (11 animals). Surprisingly, CD1a+ dendritic cells were also found within the columnar epithelium of the endocervix (5 animals). Moderate numbers of CD68+ macrophages were located in the submucosa of the vagina, ectocervix, and endocervix of all the monkeys. In all of the animals, moderate numbers of CD8+ lymphocytes were present in the submucosa and squamous epithelia of the vagina and ectocervix. Variable numbers of CD20+ B cells and CD4+ lymphocytes were located in the submucosa of all the areas examined. Lymphoid nodules were present in the submucosa of vagina (14 animals) and ectocervix (4 animals), and these nodules contained macrophages, CD4+ T cells and B cells, with fewer numbers of CD8+ T cells and Langerhans cells. CONCLUSIONS: These observations provide a morphologic basis for mucosa-associated lymphoid tissue in the female genital tract. Langerhans cells in the vaginal mucosa and endocervix may be well suited to sample antigen in the lumen of the reproductive tract, travel to the draining lymph node, present the antigen to T lymphocytes and initiate an immune response. This pathway of antigen presenting cell migration from the mucosa to the genital lymph node may represent the inductive arm of the mucosal immune system in the lower female reproductive tract. PMID- 1434541 TI - Astrocyte activation correlates with cytokine production in central nervous system of Trypanosoma brucei brucei-infected mice. AB - BACKGROUND: During the late-stage disease associated with human African trypanosomiasis, caused by infection with either Trypanosoma gambiense or T. rhodesiense, parasites invade the central nervous system (CNS), eventually leading to development of CNS pathology. This can be exacerbated by subcurative chemotherapy. The mechanisms through which the inflammatory processes within the CNS are controlled remain unclear. EXPERIMENTAL DESIGN: Mice infected with T. b. brucei were treated with a trypanocidal drug regimen on day 28 postinfection that cleared parasites from all sites except the brain. Brains of mice killed at different times during infection and after chemotherapy were analyzed, using immunocytochemistry for astrocyte activation and polymerase chain reaction assisted amplification of RNA to detect cytokine transcripts. RESULTS: Drug treated animals developed a posttreatment meningoencephalitis similar to that which can occur in humans with late-stage African trypanosomiasis. Between days 14 and 21 postinfection, before chemotherapy and the subsequent development of inflammatory lesions in the brain, astrocytes became activated. The production of several cytokines correlated with this astrocyte activation. Low levels of interleukin-1 alpha transcripts were detected in uninfected controls, but levels increased with astrocyte activation in the infected animals. Transcripts for the macrophage inflammatory protein-1 and tumor necrosis factor-alpha were first detected on day 21 postinfection, with higher levels in mice after development of the posttreatment meningoencephalitis, whereas granulocyte macrophage-colony stimulating factor was detected only in animals that developed posttreatment reaction. Interleukin-6 and interferon-gamma were also first detected on day 21 postinfection, correlating with astrocyte activation but subsequently declined with time in both treated and untreated mice. CONCLUSIONS: These results indicate that cytokines are being produced within the CNS before any inflammation and that astrocytes may be the source of some of these cytokines. Thus astrocyte activation may be key in the control and development of the CNS inflammatory processes that occur in African sleeping sickness. PMID- 1434542 TI - Characterization of high affinity binding between laminin and Alzheimer's disease amyloid precursor proteins. AB - BACKGROUND: In vivo amyloid formation apparently involves several extracellular matrix components that are usually found associated with basement membranes. These include laminin, heparan sulfate proteoglycan, collagen type IV, and entactin. These components have also been found in neuritic plaques. We have therefore been examining interactions between extracellular matrix components and the Alzheimer's amyloid precursors (AAPs). EXPERIMENTAL DESIGN: Binding interactions of laminin with AAP-695, -751, and -770 were examined using a solid phase enzyme-linked immunosorbent assay technique. RESULTS: Objective, quantitative analyses of the laminin AAP-695, -751, and -770 binding data reveal two binding sites for laminin, with Kd values of 1 x 10(-10) M and 1 x 10(-8) M. Zinc and dithiothreitol profoundly stimulate laminin binding to AAPs. Furthermore, zinc fingers were found in the laminin amino acid sequences. Previous binding studies of AAPs with the basement membrane heparan sulfate proteoglycan revealed similar affinities. A particular order of addition of laminin and heparan sulfate proteoglycan to AAPs can be demonstrated. CONCLUSIONS: These avid interactions with extracellular matrix proteins likely reflect normal functions of the AAPs and may be involved in nucleation events in Alzheimer-type amyloid formation. PMID- 1434543 TI - A new marker for rhabdomyosarcoma. Insulin-like growth factor II. AB - BACKGROUND: Accurate diagnosis of soft tissue tumors is often difficult and considered important because the clinical outcome and the modality of therapy vary according to tumor type. We have realized that rhabdomyoblasts seen in occasional Wilms' tumors express high levels of insulin-like growth factor II (IGF-II) transcripts. This observation prompted us to see if IGF-II could be a useful marker for differential diagnosis of rhabdomyosarcoma (RMS) from other soft tissue sarcomas. EXPERIMENTAL DESIGN: Five cases of RMSs (including embryonal, botryoid, and alveolar types), various other soft tissue tumors, and 10-week gestation fetal muscle tissue were studied to demonstrate IGF-II transcripts by means of Northern blot hybridization and in situ mRNA hybridization using radio-labeled probes. Hybridization results were then compared with data obtained from immunohistochemistry using antibodies against desmin and vimentin. RESULTS: Northern blot hybridization demonstrated that all five RMSs contained three major sizes of IGF-II transcripts. In situ hybridization indicated that all RMSs showed highly strong and specific IGF-II mRNA expression, whereas other soft tissue tumors showed very low or no signal. A characteristic finding was that the expression of IGF-II mRNA was inversely correlated with the degree of tumor cell differentiation. Thus poorly differentiated RMSs showed the highest signal, whereas well-differentiated RMSs showed low expression, albeit, still significantly higher than normal skeletal muscle fibers. Among five RMSs, desmin was seen in three tumors and vimentin in all tumors. Desmin was negative in other nonskeletal muscle origin tumors while vimentin was present in all tumors examined. CONCLUSIONS: IGF-II has potential as a new marker for differential diagnosis of RMS from other soft tissue tumors and could be especially useful in differential diagnosis of small blue cell tumors. PMID- 1434545 TI - Creating an agenda for school-based health promotion: a review of 25 selected reports. PMID- 1434544 TI - Multiple-modified desialylated low density lipoproteins that cause intracellular lipid accumulation. Isolation, fractionation and characterization. AB - BACKGROUND: The basic differences between sialylated (sialic acid rich) and desialylated (sialic acid poor) human low density lipoproteins (LDL) are not fully defined. It is not known whether there are any differences in the LDL composition of coronary atherosclerosis patients and healthy individuals. EXPERIMENTAL DESIGN: Sialylated (45 to 94% of total LDL) and desialylated (6 to 55%) LDL were separated by affinity chromatography on Ricinus communis agglutinin agarose, and their chemical composition and physical properties were examined. RESULTS: Sialic acid contents in sialylated LDL fractions of healthy subjects and patients were the same and 1.5 to 3-fold higher than in desialylated LDL. Desialylated LDL had smaller sizes and greater electrophoretic mobility than sialylated ones. Desialylated, but not sialylated LDL, induced 1.5- to 4-fold accumulation of neutral lipids in human aortic smooth muscle cells and human blood monocytes. Subfractions of desialylated LDL containing lower amount of sialic acid revealed higher ability to accumulate lipids in cultured cells. Desialylated LDL contained lower amounts of cholesteryl esters, free cholesterol and triglycerides as compared with sialylated LDL. On the other hand, concentration of di-, monoglycerides and free fatty acids in desialylated LDL was 2 to 3-fold higher than in sialylated lipoproteins. Desialylated LDL fraction was characterized by lower levels of phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, but higher content of lysophosphatidylcholine. Freshly isolated sialylated and desialylated LDL contained equal amounts of thiobarbituric acid reactive substances, but oxidation of desialylated LDL was more pronounced in presence of Cu(2+)-ions. Desialylated LDL had higher level of oxysterols and lower amounts of vitamin A and E. Content of free amino groups of lysine in desialylated LDL of patients was 2-fold lower than in sialylated LDL. This difference was partially due to masking of amino groups caused by conformational change in the tertiary structure of apolipoprotein, partially to chemical modification of amino groups. When subfractionated by density gradient ultracentrifugation, desialylated LDL was represented by higher density particles than sialylated LDL. Sialic acid content in desialylated LDL subfractions decreased with rise of lipoprotein density. Higher density desialylated LDL and in less extent sialylated LDL contained smaller amounts of free and esterified cholesterol and phospholipids. Only the densest subfractions of desialylated LDL from healthy subjects caused intracellular lipid accumulation. Ability of patients' desialylated LDL to accumulate cholesterol in cells increased with particle density. CONCLUSIONS: Extensive biochemical and biophysical analysis performed in this study shows that desialylated LDL differ from these sialylated LDL in many respects. The LDL of coronary atherosclerosis patients differ from those in healthy individuals in several parameters. PMID- 1434546 TI - Use of a school referendum to deter teen-age tobacco use. AB - Montana's 1991 school "tobacco referendum," authorized by the state legislature and approved by about 60% of approximately 50,000 students voting in grades 7-12, represents an innovative attempt to include youth in decisions regarding tobacco and health and to decisively demonstrate peer disapproval of tobacco use. The referendum asked students whether tobacco sellers should voluntarily refuse to sell cigarettes and tobacco to persons younger than age 18. Montana is one of five states which allow tobacco sales to minors but has one of the nation's lowest youth smoking rates. The statewide referendum follows the successful example of the Bozeman, Montana, school district's 1990 tobacco referendum, in which 80% of the 2,200 grade 7-12 students and staff voted to make their schools "tobacco-free." PMID- 1434547 TI - Susceptibility to peer pressure as an explanatory variable for the differential effectiveness of an alcohol misuse prevention program in elementary schools. AB - A school-based alcohol misuse prevention program had differential effects on students' susceptibility to peer pressure, depending on prior experience with alcohol. These effects paralleled those on alcohol use and misuse, indicating program effects on use and misuse were mediated by reductions in the rate of increase on susceptibility to peer pressure. Experimental group students with prior unsupervised use of alcohol showed a significantly greater reduction than their controls in the rate of increase in susceptibility to peer pressure, alcohol use, and alcohol misuse. This difference was not found among students without prior unsupervised use of alcohol. PMID- 1434548 TI - Peer perceptions of adolescent health behaviors. AB - Perceptions adolescents form of peers in relation to modeled health behaviors were examined. Five hundred ten adolescents, ages 12-15, from eight midwest schools were shown a slide of a male or female adolescent displaying a health behavior artifact (apple, tennis racket, cigarette, beer can), or without an artifact and asked to rate the model on 16 characteristics using a semantic differential scale. Data were factor analyzed using principle components analysis and a 2x2x5 MANOVA. Results indicated that models appeared less mature when holding a beer can or cigarette. In addition, the female model was rated more popular than the male in the control and beer can depictions. The influence of modeled behaviors on traits adolescents want to develop must be understood to present effective health education programs. Educational efforts should include consideration of the perceptions adolescents hold of their peers' health behaviors. PMID- 1434549 TI - HIV-infected students in school: who really "needs to know"? PMID- 1434551 TI - Selected tobacco-use behaviors and dietary patterns among high school students- United States, 1991. PMID- 1434550 TI - Community-oriented primary care: a process for school health intervention. PMID- 1434552 TI - Demographics of adolescent sexual behavior, contraception, pregnancy, and STDs. AB - The demographics of fertility-related behavior of youth ages 10-18 are reviewed. Data were collected from U.S. vital statistics, and birth rates, contraceptive use, sexual behavior, number and types of sexual partners, patterns of sexual initiation and sexual intercourse, and sexually transmitted diseases were examined. Despite data limitations, the demographic profile of adolescent sexual intercourse is striking. Age clearly is the single most important predictor of sexual debut. PMID- 1434553 TI - Risk factors for adolescent sexual behavior, fertility, and sexually transmitted diseases. AB - Current understanding of the risk factors related to adolescent initiation of sexual activity, use of contraception, pregnancy, and STDs is examined. From recent research on adolescent fertility, findings that have particular relevance to school health or reflect new understandings of adolescent sexuality are summarized. In selected cases, prevention programs that build directly on an understanding of these risk factors are cited. PMID- 1434555 TI - Teen contraception in the 1990s. AB - Basic information about appropriate contraceptive methods for teen-agers is provided. Methods most commonly used will be reviewed and an overview of alternative methods available for use in special subgroups will be provided. PMID- 1434554 TI - School-based programs to reduce sexual risk-taking behaviors. AB - This article reviews the major approaches implemented during the last two decades to reduce sexual risk-taking behaviors, examines their evidence for success, and provides several recommendations for effective programs and program evaluations. This article does not discuss more broad-based sexuality education programs which address sexuality in a broader context. Instead, this article focuses primarily on programs that educators believed would reduce unprotected sexual intercourse. PMID- 1434556 TI - Adolescent reproductive health: roles for school personnel in prevention and early intervention. AB - The practical roles school staff can play in addressing adolescent reproductive health issues such as teen-age pregnancy, STDs, and HIV/AIDS are reviewed. Particular attention is given to identification and assessment of adolescents most at risk for pregnancy, STDs, and HIV/AIDS, and the regulations that address protection of students' privacy in this area. PMID- 1434557 TI - Adolescent pregnancy options. AB - The range of pregnancy options available to adolescents each have significant ramifications for future educational and economic achievement. The changing societal context of adolescent pregnancy decision-making are described, and the characteristics of adolescents who choose to terminate their pregnancy, parent their child, or place for adoption are examined. The role of significant others in decision-making and the implications of mandatory parental involvement in pregnancy decision-making is discussed, as well as the roles of schools in promoting the well-being and potential of adolescents considering pregnancy decisions. PMID- 1434558 TI - School-based prenatal and postpartum care: strategies for meeting the medical and educational needs of pregnant and parenting students. AB - Adolescent pregnancy is not a new phenomenon, but it is a source of concern to U.S. educators because of the many young women choosing to become parents and the profound effect early childbearing has on the educational and vocational careers of many young Americans. Strategies for addressing the unique medical, educational, and psychosocial needs of pregnant and parenting students will be examined. Documented physical and psychosocial risks associated with adolescent childbearing will be reviewed, and data related to the effect of young maternal age on pregnancy outcome and the effect of pregnancy on the life course development of adolescents will be emphasized. Specific elements of comprehensive, adolescent-oriented prenatal and postnatal care will be discussed, as well as the effectiveness of existing prenatal and postnatal programs at preventing the most serious sequelae of adolescent childbearing. The role of school-based services will be examined, and ways will be discussed for educators and health care providers to collaborate in providing medical, educational, and social services for adolescent parents and their children. In addition, topics for future research will be suggested. PMID- 1434559 TI - Consequences of teen-age parenting. AB - The changing context of teen-age childbearing and current related controversies are reviewed. Recent research about the consequences of teen-age childbearing for the teen-age mother, the father, and for the children born is examined. The article also summarizes current knowledge about the consequences of teen-age childbearing with regard to the mother's educational attainment, marital experience, subsequent fertility behavior, labor force experience and occupational attainment, and experience with poverty and welfare. PMID- 1434560 TI - Abortion among adolescents: research findings and the current debate. AB - Utilizing research that focuses on adolescents as well as findings in samples which might have special relevance to young, unmarried women, this report summarizes research on the consequences of abortion among adolescents. It discusses prior literature in the area of parental notification and parental consent, subjects on which public opinion is not divided along familiar pro choice/anti-choice lines. Following a discussion of methodological problems identified in prior research, it reports on a study designed to address these problems in an adolescent population; it discusses implications for the current debate of this and other studies' findings that there are no identifiable adverse sequelae of the abortion process. PMID- 1434561 TI - Epidemiology of AIDS, HIV prevalence, and HIV incidence among adolescents. AB - Health educators, policy analysts, and public health officials are becoming more aware of the serious threat HIV poses to the health of U.S. adolescents. While AIDS among adolescents remains relatively uncommon, considerable data indicates this age group has alarmingly high HIV infection rates and that minority adolescents are at disproportionately greater risk of HIV infection relative to their White peers. Recent seroconversion studies of active duty military personnel indicate that the number of new HIV infections (incident cases) are especially high among Black adolescents. Findings suggest the urgent need for more tailored HIV prevention programs, especially gender- and ethnic-specific programs. PMID- 1434562 TI - Adolescents and sexually transmitted diseases. AB - Sexually transmitted diseases (STDs) are a serious health problem for adolescents, occurring in an estimated one-quarter of sexually active teen-agers. Many of the health problems--including STDs--result from specific risk-taking behaviors. Determinants of STD risks among adolescents include behavioral, psychological, social, biological, institutional factors. Education is an important component in STD control in adolescents. The goal of education is to increase adolescent self-efficiency in practicing STD prevention and risk reduction. A comprehensive approach including quality, theory-based education, accessible and effective health clinics, and improved social and economic conditions has the most promise of controlling STDs in adolescents. PMID- 1434563 TI - Making sexuality education and prevention programs relevant for African-American youth. AB - A demographic and cultural profile of African-American youth is presented. Culturally-based differences in decision-making are reviewed. Attitudes and cultural values related to identity and self-image, gender role socialization, contraception, marriage and parenthood, homosexuality, and HIV/AIDS are described. Recommendations and strategies to make sexuality education and pregnancy prevention programs relevant to African-American youth are offered. PMID- 1434564 TI - Adolescent pregnancy prevention for Hispanic youth: the role of schools, families, and communities. AB - A sociodemographic profile of Hispanic youth is presented as well as a description of the incidence of adolescent pregnancy and parenting in this population. Strategies and recommendations that should be implemented to provide Hispanic youth with viable options and assistance in delaying early childbearing also are offered. PMID- 1434565 TI - Creating a safer school environment for lesbian and gay students. AB - Information obtained from clinical experiences of the University of Minnesota Youth and AIDS Project (YAP), a primary AIDS prevention program for gay and bisexual males ages 14-21, is described. More than 300 YAP clients have been interviewed regarding sexual behavior, suicide attempts, drug use, and experiences in disclosing their homosexuality to peers and parents during their high school years. The authors also have drawn from their experiences as support group leaders for gay, lesbian, and bisexual youth in high school and community settings. Constructive and destructive coping strategies employed by gay, lesbian, and bisexual students are described. Roles and responsibilities of school professionals to create a safer school environment also are presented. Key issues include how school professionals support or deny the existence of homosexuality in young people; how adults' biases against homosexuality, as well as institutionalized heterosexism, prevent lesbian and gay students from succeeding in school; how language, behaviors, and environmental cues contribute to school professionals' approachability; how children of lesbian and gay parents suffer when negative attitudes toward homosexuality are not challenged; and what resources and referrals can help lesbian and gay young people. PMID- 1434566 TI - Sensitivity coefficients, trajectories and graphs of a human head-movement model. AB - With time as the criterion to be optimized, the divergences from optimal head movements show systematic differences in their control signal variables with respect to single behaviours. To clarify these relationships, this study applies manipulation and mathematical analysis of the 6th-order nonlinear head movement model, using the three-fold approach of sensitivity analysis. The sensitivity analysis of the improved and refined head movement model explains the different tasks of the control parameters and their relation to the plant. It shows that width more than height of the agonistic and antagonistic pulses dominate the important behaviours of the movement: acceleration, magnitude and duration. PMID- 1434567 TI - Analysis of electromagnetic heating patterns inside a cryopreserved organ. AB - Computer analysis of the induced electromagnetic field and heating distribution inside cryopreserved organs subjected to electromagnetic illumination at frequencies of 84 MHz, 434 MHz and 2.45 GHz were carried out using a spherical model for the organ, with special reference to heating in a single-mode resonant cavity. The interaction between the frequency of the incident field and the size and dielectric properties of the sample was investigated. It is shown that uniform heating of organs is likely to be achieved at lower frequencies, as might be expected. However, the ratio between the power penetration depth for plane waves and the size of the organ is not a sufficient basis on which to judge quantitatively the uniformity of the power absorption. Hot or cold spots can occur within the organ even when this ratio is greater than unity; the wavelength in the material is also an important factor. The results from this study indicate that the use of a resonant cavity as a heating applicator has advantages over plane-wave illumination. A sharp upper limit can be set to the frequency suitable for rapid and uniform heating of a given organ. PMID- 1434568 TI - Finite element stress analysis of simulated metastatic lesions in the lumbar vertebral body. AB - A three-dimensional finite element model of a lumbar vertebral body was developed to study the effects of geometry, material properties and loading conditions on stresses in the presence of metastatic lesions. Parameters studied included location and size of the lesion, modulus of the cortical and trabecular bone within and near the lesion, generalized osteoporosis and load distribution. The results, expressed as ratios of peak values of displacement and stress, relative to a normal baseline case, indicated that the location of a defect which did not penetrate the cortex had a minor influence on the peak displacement and stresses, as did the presence of lesions occupying less than 40% of the volume of the vertebral centrum. A lesion occupying 40% of the centrum volume increased the endplate displacement by 2.9 times, the peak tensile stress in the cortical shell by 2.2 times, and the peak von Mises stress in the endplate by 2.8 times. When this lesion penetrated the cortex, these values increased to 3.8, 3.3 and 4.4 times, respectively. The most severe case involved a defect penetrating the anterior cortex, osteoporotic bone properties and anteriorly eccentric loading. In this case, the peak values increased to 8.4, 3.4 and 5.9 times their baseline values, respectively. The results are consistent with a model of the vertebral body as a stiff frame of cortical bone surrounding a relatively compliant core of trabecular bone. Only variations in geometry and properties large enough to lessen significantly the structural stiffness affect the peak stresses and displacements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434569 TI - Performance of a 7-parameter DLT method for the calibration of stereophotogrammetric systems using 1-D transducers. AB - A method is presented for calibrating stereophotogrammetric systems which are based on 1-D cameras, i.e., able to record only one of the two coordinates relative to the projection of the target point onto the image plane of a camera. This procedure is based on the Direct Linear Transformation, DLT, introduced by Marzan and Karara. The present version (7DLT) is different from the standard 11 parameter DLT (11DLT); it avoids certain non-orthogonality problems arising in usual DLT implementations, whose correction can be obtained by modifying the basic algorithm, at the expense of its simplicity (MDLT). The accuracy assessment of the 7DLT method was carried out both by a computer simulation of a two-camera stereophotogrammetric system, and on real data from three 1-D optoelectronic cameras. The computer simulation permitted us to compare the performance of 7DLT with 11DLT and MDLT. The reconstruction accuracies of the three algorithms were quite similar. When using real 1-D data, a reconstruction accuracy of 0.66 mm RMS error was obtained (mean value for X, Y, Z coordinates) for 18 target points used as calibration control points. The extrapolation accuracy was 1.85 mm RMS for 180 target points lying outside the calibration structure. PMID- 1434570 TI - Three-dimensional finite element modelling of bone: effects of element size. AB - This study quantifies the effects of element size on the stress/strain results of finite element (FE) models of bone that are generated with a previously described automated method. This method uses cube-shaped hexahedral elements, which enabled element shape and aspect ratio to be held constant while the effects of element size were studied. Three models of a human proximal femur, each with a different element size (3.1 mm, 3.8 mm and 4.8 mm), were analysed. Convergence in strain energy of the models had been verified in previous work. The stresses and strains predicted by the models were compared on a pointwise basis using linear regression analysis. There was a general decrease in the level of stress and strain when element size was increased, even though convergence in strain energy had been achieved. An increase in element width from 3.1 mm to 3.8 mm decreased the predicted stresses by 13% to 29% overall; the predicted strains decreased by 4% to 20% for the same increase in element size. These results indicate that linear cube-shaped hexahedral elements must be very small (3 mm on a side or smaller) to represent the sharp variations in mechanical properties that exist in bone, and that use of larger elements decreases the predicted stresses and strains. The elements used in this study are similar to those typically used to represent trabecular bone in conventional (non-automated) FE modelling methods. Therefore, the sensitivity of the stress/strain results to element size that was found for trabecular bone also applies to conventional modelling of such bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434571 TI - Use of uncalibrated biplanar radiography for the measurement of skeletal coordinates around the shoulder girdle. AB - Mechanical modelling of the musculoskeletal system is dependent upon information regarding the bony attachments of the relevant muscles; in order to study the biomechanics of the shoulder girdle the authors have identified the muscle attachments in three embalmed cadavers. A simple biplanar radiographic technique was then used to determine the attachment coordinates using frames of reference defined for each bone. This technique, using hand positioning without special fixtures was believed to be sufficiently accurate, bearing in mind the likely degree of biological variation. In order to test this assumption, the accuracy of the technique has been studied by measuring the agreement between the two measurements of the common coordinate in the pairs of radiographs. It was found that for the trunk, the errors in the common coordinate were always less than the natural variation; for the scapula they were of a similar magnitude but, for the humerus, the measurement errors frequently exceeded the variation in the coordinates of muscle attachments. It was concluded that, in general, uncalibrated biplanar radiography was sufficiently accurate for the determination of the spatial coordinates of muscle attachments. PMID- 1434572 TI - Development and validation of a new transducer for intradiscal pressure measurement. AB - Potentially damaging tensile stresses in the annulus fibrosus are directly related to the hydrostatic pressure in the centre of an intervertebral disc: the design and development of a miniature strain gauge pressure transducer is described for measuring such pressures. Static calibration tests in bulk liquid demonstrated that measurements made with the transducer were of sufficient accuracy and stability for in vitro and in vivo investigations of spinal mechanics, and a study of the dynamic behaviour of the transducer demonstrated that it had a frequency response suitable for in vitro and in vivo investigations. Tests within loaded cadaveric discs showed that the transducer could be used to make repeatable measurements which were free from significant artefacts, when the disc was subjected to forces of up to 4000 N and when deformed in full flexion/extension. PMID- 1434573 TI - Design of intramedullary prostheses to prevent bone loss: predictions based on damage-stimulated remodelling. AB - The adaptation of bone around intramedullary fixated prostheses, such as the femoral component of the hip joint or the radial component of the elbow joint, is well documented in follow-up studies. Bone adaptation takes the form of proximal bone atrophy accompanied, in some cases, by distal bone hypertrophy. A mechanistic model has been formulated to predict bone adaptation based on the concept that the continuous processes of damage and repair regulate bone adaptation. We apply the model to investigate the significance of two features of intramedullary prosthesis design on bone adaptation: prosthesis Young's modulus and the presence of a prosthesis collar. Results, as well, as indicating some characteristics of accumulative-damage stimulated bone adaptation, predict that a low Young's modules stem will very much reduce the extent of bone loss whereas the presence of a collar will have no significant effect. The results predict that a collarless low stiffness prosthesis is one possible approach for improving the secondary stability of intramedullary-fixated orthopaedic implants. PMID- 1434574 TI - Running discrete cosine transform. AB - The discrete cosine transform (DCT) has become an important tool in digital signal processing because its performance is close to the optimal Karhunen-Loeve transform. In this work the running discrete cosine transform (RDCT) is introduced. Using the properties of the discrete Fourier transform kernel W = exp (-2 pi j/N), a fast recursive algorithm was developed for real-time computation of the RDCT coefficients. For N-point RDCT the present algorithm needs only 2N real multiplications. The hardware implementations of the RDCT algorithm and applications in real-time data processing are discussed. PMID- 1434575 TI - Universal joint slippage as a cause of Hoffmann half-frame external fixator failure [corrected]. AB - Slippage of the universal joints of external fixation devices is known to occur but its significance or incidence is often overlooked. In this study, controlled experiments were used to determine the relationship between joint slippage and the maximum loads a single half-frame could bear for the Hofmann device. The experiments showed that: (a) the joints slipped at minimal loads and (b) frame failure, i.e. loss of initial alignment of the frame components, was determined by joint slippage. The importance of the control of slippage cannot be overstated; the orthopaedic community must educate itself and its patients and guard against the problem in order to avoid complications secondary to slippage. PMID- 1434576 TI - Correlation algorithm and sampling techniques for estimating the signal-to-noise ratio of the electrocardiogram. AB - An algorithm, based on correlation techniques, is proposed for estimating the signal-to-noise ratio of very low frequency signals contaminated by white and flicker noise. Sampling techniques based on converting a single continuous signal into two time series that satisfy the requirements of cross-correlation functions are proposed. The algorithm has been tested on simulated data and the electrocardiogram transduced from ten patients. PMID- 1434577 TI - Drug recirculation model with multiple cycles occurring at unequal time intervals. AB - A pharmacokinetic model for enterohepatic recycling has been developed to take into account multiple recirculations likely to occur at various times after intravenous or subcutaneous injection, after infusion, or after a single oral administration of a drug. The times when the gall bladder empties, the duration of infusion and the number of recirculations may be arbitrarily chosen (for simulations) or computed (for optimization) to express the concentration in the central compartment at any time. Without a new theoretical calculation, the area under the concentration curve may be obtained as a function of the model parameters. As an example, the model is applied to an experimental case of four recirculations after oral administration and to a new drug data fitting. PMID- 1434578 TI - Forces required for dilatation of human cervix in first trimester of pregnancy. AB - Cervical resistance to dilatation was measured in 76 patients undergoing first trimester legal abortion; a specially designed force-sensing instrument was used. No correlation between cervical resistance and patient age or gestational age was found. Increasing parity and earlier legal abortions were significantly correlated with a lowering of the cervical resistance. In patients dilated to 11 mm a lowering of resistance was noted suggesting a tear in cervical tissue. PMID- 1434579 TI - The relationship between anaerobic running capacity and peak plasma lactate. AB - The purpose of this study was to examine the relationship between anaerobic running capacity and peak plasma lactate. Twelve adult males (mean age +/- SD = 21.9 +/- 1.2 yrs) performed a critical velocity test from which anaerobic running capacity was determined and a maximal treadmill running test from which peak plasma lactate was determined from post-exercise blood samples taken at one minute intervals. The results indicated that anaerobic running capacity (mean +/- SD = 0.18 +/- 0.04 km) was not significantly (r = -0.06, p greater than 0.05) correlated with peak plasma lactate (9.3 +/- 1.8 mM). These findings do not support anaerobic running capacity as an indirect indicator of anaerobic capabilities. PMID- 1434580 TI - Energy expenditure following a bout of non-steady state resistance exercise. AB - Little is known about the effect of non-steady state resistive exercise on postexercise energy expenditure. Using a counterbalanced design, energy expenditure was measured by indirect calorimetry in six adult males (mean age +/- SD = 24.5 +/- 6.1) for 30 min before and 60 min after a single 42 min bout of weight lifting, and again on a separate day for 30 min before and 60 min after a 42 min control period of quiet sitting. For the exercise condition the subjects performed 4 sets of upper and 3 sets of lower body resistive exercises at weights equivalent to a 12 repetition maximum for each respective lift. Metabolic rate remained significantly elevated at the end of the 60 min recovery period compared to the control condition, although the excess postexercise oxygen consumption accounted for only approximately 19 additional kcal expended. These data suggest that while postexercise metabolic remains elevated for at least one hour following a moderate level of resistive exercise, the caloric cost of this elevation during a one hour recovery period is small and similar to that induced by steady-state exercise of moderate intensity. PMID- 1434581 TI - Is aerobic dance an effective alternative to walk-jog exercise training? AB - In order to compare the physiological effects of an 8 week aerobic dance program to those of a walk-jog exercise training program, 60 male and female University employees ages 24-48 years were randomly assigned to an aerobic dance program (N = 22), a walk-jog program (N = 24), or a sedentary control group (N = 15). Subjects who had an exercise compliance rate less than or equal to 85% were dropped from the study, as were control subjects who had scheduling conflicts or illnesses precluding post-treatment testing. Thirty-five subjects completed the 8 week period with a compliance rate greater than or equal to 85%, leaving 14 in the aerobics group, 11 in the walk-jog group and 10 in the control group. Significant increases (p less than 0.001) in maximal oxygen uptake occurred in both the aerobics (+3.9 ml/kg-1/min-1) and walk-jog group (+3.4 ml/kg-1/min-1), while no significant change was observed in the control group. Peak heart rate decreased significantly (p less than 0.05) in the aerobics (-4 b/min-1) and walk jog groups (-3 b/min-1 but was unchanged in the control group (-1 b/min-1) following the treatment period. Body weight, peak respiratory exchange ratio and peak minute ventilation remained the same in the aerobics, walk-jog and control groups throughout the treatment period. It is concluded that aerobic dance programs can result in similar improvements in aerobic power as a walk-jog program. Thus, an aerobic dance program is an effective alternative to a traditional walk-jog training regime. PMID- 1434582 TI - Biological and performance variables in relation to age in male and female adolescent athletes. AB - To observe the cross-sectional nature of the effect of age, height, and body mass on motor performance during adolescence (13-18 years), 103 boy and 65 girl athletes were measured for motor performance and anthropometric variables. Motor performances included tests of strength, muscular endurance, flexibility, aerobic capacity, anaerobic power, speed, and agility. Anthropometric determinations included height, body mass, lean body mass, %fat, and somatotype. Boys were significantly different from girls in all measurements except endomorphy, while girls were significantly superior to boys only in flexibility. Physical maturation, as reflected by height and body mass, was a major contributor to increases in motor performance. Somatotype did not differ greatly across the age groups. Boys were significantly more mesomorphic than girls, while girls were significantly more ectomorphic than boys. Higher %fat and more endomorphy were significantly related to poorer performance for relative aerobic capacity, 40-yd dash, and agility in boys but only for upper body muscular endurance in girls. Mesomorphy had higher relationships with performance variables among boys than among girls. Growth would appear to contribute significantly to enhanced motor performance with age, and its effect may be different in boys than in girls. PMID- 1434583 TI - A physiological and nutritional profile of young female figure skaters. AB - This study was undertaken to develop a physiological and nutritional profile of 13 female figure skaters, aged 9-17 years. Compared with previous published data, skaters in this study were younger and smaller with a higher percent body fat. Skaters in this study were less experienced and trained less than skaters in other studies but attained similar levels of maximal oxygen uptake (VO2max), handgrip strength, and vertical jump power. Relative VO2max (ml/kg/min) was significantly negatively correlated (p less than 0.0033) with body weight and percent body fat, while body weight was significantly positively correlated (p less than 0.0003) with handgrip strength and vertical jump power. In terms of nutritional recommendations, skaters in this study consumed comparatively high amounts of fat and protein with low amounts of carbohydrate, calcium, and iron. Despite suboptimal nutrition and a relatively low training volume, skaters in this study exhibited physiological characteristics similar to those reported for female figure skaters in the literature. PMID- 1434584 TI - Body composition and energy metabolism in resting and exercising muslims during Ramadan fast. AB - Muslims abstain from food and drink from dawn to sunset during Ramadam, the ninth month of the Islamic calendar. The purpose of this study was to examine the changes that occurred in body composition and both resting and exercise metabolism during a 4 week Ramadan fast. Subjects consumed an average of 1220 kcal each day during Ramadan and lost a significant 1.92 kg body weight. The subjects also lost 2.8% fat. Fat-free mass did not change. Serum sodium, chloride, and protein increased during the first week of Ramadan and returned to the pre-fasting levels during the last week. This indicates a state of dehydratation existed during the first week of Ramadan. Consistent with this is first week 1.13 kg body weight loss with no change in percent fat. First week Ramadan tests showed a significant decrease in VO2max with a return to the pre test levels in the last week. The lower resting afternoon VO2 suggests that during Ramadan the body's metabolism slows down during the day in order to conserve its energy stores, however, exercise economy as measured by submaximal VO2 in mk/kg/min is not affected. PMID- 1434585 TI - Physiological assessment of Saudi athletes. AB - This study was aimed at assessing the physiological responses of Saudi male athletes to maximal exercise testing. Seventy five national athletes representing nine different sports and fourteen healthy controls were subjected to graded bicycle ergometer tests, during which cardiorespiratory and metabolic functions were monitored and recorded. The results of this study indicate that the maximal oxygen uptake (VO2max) values for the Saudi athletes were not significantly different from those of controls. The cyclists, however, attained the highest VO2max with a mean of 55.05 ml.kg-1.min-1 followed by the middle distance runners (X = 53.17) and the long distance runners (X = 51.19). Comparison of the Saudi athletes with some previously reported international standards revealed that the Saudi athletes had a VO2max that was lower than their respective French, Swedish, Belgian, Norwegian, Italian, Canadian or American athletes. PMID- 1434586 TI - Effect of body position on the afterload response during sustained exercise. AB - Hemodynamic and cardiovascular responses were studied in 80 males (age: 30 +/- 2 years) at rest, and during separate three minute trials of upright and supine isometric deadlift exercise at 30% of maximum voluntary contraction (MVC). MVC did not differ significantly between supine and upright deadlift exercise. In comparison to values at rest, both forms of isometric exercise resulted in significant increases (p less than 0.05) in heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, oxygen uptake, oxygen pulse and double product. In the upright exercise, the values obtained for all of the physiological variables were found to be significantly higher (p less than 0.05) than in the supine exercise. These findings indicate that the upright isometric deadlift produces a higher after-load than the supine maneuver, and that this response may be a good indicator of cardiovascular functioning. PMID- 1434587 TI - Effect of musculoskeletal development on the prediction of body density in females. AB - The purpose of this study was to determine if musculoskeletal development had a significant effect on the prediction of body density in females. Subjects consisted of 156 females aged 17 to 44 years. Subjects were divided into three groups on the basis of musculoskeletal development as determined by the Heath Carter Anthropometric Somatotype mesomorphy rating. Anthropometric measurements included eight skinfold measures (tricep, subscapula, chest, midaxillary, abdomen, suprailiac, thigh, and calf), body diameters of the humerus and femur, and circumferences at five locations (waist, forearm, upper arm, calf, and gluteal). Residual lung volume was determined by the closed circuit oxygen dilution method prior to the measurement of body density by hydrostatic weighing. A regression equation was developed to predict body density from the sum of seven skinfolds, sum of seven skinfolds squared, age, and mesomorphy rating. A similar regression equation was developed using the sum of three skinfolds, sum of three skinfolds squared, and the other variables. Results indicated that mesomorphy rating did not contribute significantly to the prediction of body density in females. It was concluded that musculoskeletal development did not have a significant effect on the prediction of body density in females. PMID- 1434588 TI - Serum enzymes activities at rest and after a marathon race. AB - With the purpose of determining the long and short term changes in serum enzyme activities after a marathon race, a survey involving nine healthy male runners was carried out. A basal blood sample was extracted from each 24 hours prior to the race and three further extractions were made immediately after the race, as well as at 1 and a final 24 h after the end of the race. In the enzymes of preferably hepatic origin--alkaline phosphatase (AP), ganna-glutamyltransferase (GGT) and alanine aminotransferase (ALT)--scanty modifications were found and these could be related to the changes observed in the plasma volume. Enzymes such as aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), which are widely distributed in the tissues, were found to have undergone more marked variations and these could not be related to the changes in the volume of the plasma, while in enzymes of muscular origin such as aldolase (ALD), creatine kinase (CK) and its cardiac isoenzyme (CK-MB), notable increases were observed due to the muscular injury suffered. The greatest example of this was the increase found in total CK 24 h after the end of the marathon (414.6%). The high serum percentages found in CK-MB in these endurance-trained runners in relation to total CK activity should be carefully assessed in order to avoid false diagnosis of acute myocardial infarction. PMID- 1434589 TI - Monitoring training status in professional ballet dancers. AB - Methods of non-invasive monitoring of training status for prevention of staleness in athletes and dancers need to be developed and evaluated. In order to monitor physiologic and psychologic changes which may result from overstraining, we measured urinary excretion of free norepinephrine (NE) and epinephrine (E) and mood states over 5 weeks of an intensive ballet season in 12 (6 men, 6 women) professional dancers. First morning urine voids (AM) were collected at the start of the season and following the only off-day each week with final collection on the last day of the season. Additional urine samples were collected before (pre) and after (post) each dancer's subjectively-rated single most difficult performance. Profile of Mood States (POMS) was completed by and collected from each dancer at the same time as the AM urine samples. NE and E excretions (nanograms per mg creatinine) increased significantly with time (r = 0.91, p less than 0.02, and r = 0.94, p less than 0.01, respectively) from beginning to end of season, and pre to post (51.1 +/- 7.3 to 115.6 +/- 19.7, p less than 0.001 and 19.3 +/- 3.2 to 37.7 +/- 4.2, p less than 0.001, respectively). Women had a significantly higher excretion of NE than did men (F = 9.33, p = 0.014) and no gender differences existed in the excretion of E (F = 0.57, p = 0.484).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434590 TI - Urinary protein excretion induced by exercise: effect of a mountain agonistic footrace in healthy subjects. Renal function and mountain footrace. AB - The increase in albuminuria induced by exercise in healthy subjects is variably dependent on an increased glomerular filtration and/or to a decreased tubular reabsorption of albumin, in relation to the intensity of muscular work. Membrane anionic charges and haemodynamic changes have been implicated in exercise-induced albuminuria. We evaluated in 12 healthy subjects albumin and beta-2-microglobulin excretion rate and the presence in urine of cationic compounds before and after an agonistic mountain footrace. Albumin excretion rate increased significantly (3.7 +/- 1.3 vs 43.7 +/- 10.0 micrograms/min) (p less than 0.001) and beta-2 microglobulin excretion rate (16.5 +/- 4.4 vs 37.9 +/- 7.4 micrograms/min) (p less than 0.025), too. In 3/4 subjects, urines revealed a peak of highly cationic proteins, sharing antigenic and biological characteristics with platelet-derived cationic proteins. The increase in albuminuria induced by strenuous exercise of an agonistic mountain footrace is of mixed type (both glomerular and tubular) and is associated to the urinary excretion of cationic proteins. PMID- 1434591 TI - The Kaike triathletes' hematocrit values. With relation to their competition results. AB - The subjects were 20 male triathletes in the 4th Kaike Triathlon, held in Tottori during 1984. The competitors' hemogram values were estimated at rest, during, and after the competition. The results were related to their competition order by methods of rank correlations and cluster analysis, using the average distance method. The first cluster, including an competition order is composed of hematocrit at rest, after swimming, after bicycling, and after the finish. The rank correlation coefficients between competition order and hematocrit values were significant (p less than 0.05) at each of the four periods, especially after swimming, though the probability is the same. We found that lower hematocrit values correlate with excellent competition results, as the competitors' hematocrit values could be elevated during exercise if their hematocrit values are in the low normal density whilst at rest. PMID- 1434592 TI - Physical activity, physical fitness and mortality in a sample of middle aged men followed-up 25 years. AB - One-thousand-seven-hundred-twelve men aged 40-59, representing two demographic samples of rural areas in Northern and Central Italy, were examined in 1960 and then followed-up for 25 years. Total mortality and coronary mortality were related to the entry measurements of physical activity at work, estimated in three levels by a simple questionnaire and to four possible indicators of physical fitness, ie resting heart rate, the circumference of the right arm cleaned from the contribution of skin and subcutaneous fat, vital capacity and forced expiratory volume in 3/4 sec, the latter two adjusted by height. The four indicators of fitness and the score of physical activity were somewhat related each other in the expected direction. Both all causes and coronary mortality were indirectly related to the score of physical activity. The relative risk for age adjusted rates of sedentary vs heavy workers was 1.23 for all causes of death, and 1.72 for coronary deaths. Direct univariate relationships were found between resting heart rate and mortality (for both all causes and coronary deaths) whereas indirect relationships were found for arm circumference and the two indicators of respiratory function. The age adjusted relative risks between the upper and the bottom quartile of the distribution were, for all causes of death, 0.75 for vital capacity, 0.68 for forced expiratory volume 1.32 for heart rate, and 0.84 for arm circumference. The correspondent relative risks for coronary deaths were 0.71, 0.65, 1.23 and 1.02 respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434594 TI - The effect of dexamethasone and endotoxin administration on biliary IgA and bacterial adherence. AB - Adherence of bacteria to the intestinal epithelial cell may be the crucial initiating event for invasion and translocation and is normally prevented by both immune (IgA) and nonimmune (mucus, peristalsis, desquamation) mucosal defense mechanisms. The purpose of the present study was to examine the effect of endotoxin administration on mucosal immunity and to define the role of glucocorticoids, commonly released during endotoxicosis, in this process. Thirty female Fisher rats were randomly assigned to three groups of 10 animals each. Group I (CONT), was fed rat chow and H2O ad lib., Group II (DEX) was administered 0.8 mg/kg subcutaneously of dexamethasone, and Group III (ETX) was given 1 mg/kg of endotoxin. Twenty-four hours later animals were sacrificed and mesenteric lymph nodes and vigorously washed stool-free ceca were collected and cultured. Bile was collected and assayed for IgA from 5 animals in each group. A significant decrease (P < 0.05) in secretory IgA was noted in animals treated with either dexamethasone or endotoxin (CONT = 332 +/- 42, DEX = 78 +/- 24, ETX = 68 +/- 16 micrograms/mg protein +/- SEM). No difference in S-IgA between animals in the dexamethasone-treated group and the endotoxin-treated group was noted (P = NS). A statistically significant increase (P < 0.001) in bacteria adherent to the cecal wall in both the dexamethasone-treated rats and the endotoxin-treated rats over that in = 7.5 +/- 0.8, CONT = 6.4 +/- 0.6 cfu/g(log10) +/- SD). Our results suggest that endotoxin or glucocorticoid administration results in significant bacterial adherence to the cecal mucosa and a decrease in IgA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434593 TI - Trends in sports injuries, 1982-1988: an in-depth study on four types of sport. AB - In this study, we analyzed the records of both inpatients and outpatients which were treated for acute sports injuries in the Trauma Department of the University of Groningen (The Netherlands) during the years 1982 to 1988. We examined whether there was a trend in sports injuries in this time period. The study comprised four types of sports, i.e., soccer, volleyball, gymnastics, and martial arts. The absolutely highest rates of injuries across the seven years were found in soccer, followed by gymnastics, volleyball, and martial arts. Injuries sustained at participating in soccer, volleyball, and gymnastics involved for the major part the lower extremities, followed by injuries of the upper extremities, whereas the reverse pattern was observed for patients who participated in martial arts. For all four types of sport, the ankle and foot were the most frequently site of injury of the lower extremities. Sprains and strains were the major types of injury. Most injuries were seen at ages between 10 and 30 years. The ratio of male to female patients within age groups did not differ significantly across the seven years. We concluded that, except for martial arts, the increased participation in sports in the last decade was not accompanied with a change in the patterns of sports injuries by the patients' age, sex, and number and nature of the injury. This consistency in results can be used to guide the development of prevention programs aimed at a reduction of injuries in specific sports. PMID- 1434595 TI - Evaluation of a rat model for the study of local regulation of intestinal blood flow: ex vivo asanguineous perfusion of the ileal vascular bed. AB - A new model of ex vivo vascularly perfused, isolated rat ileum was developed and evaluated. Segments of distal ileum (approximately 5 cm) from male Wistar rats were isolated on their vascular pedicles. Perfusion through an aortic cannula with oxygenated (95% O2, 5% CO2) Krebs solution containing 5% bovine albumin, 5.6 mM glucose, and 25 mM mannitol at 37 degrees C was initiated immediately after interruption of blood flow. The bowel preparations, including the abdominal aorta, were then transferred to a perfusion chamber. Perfusion pressure was maintained by gravity at 40 mm Hg. Flow was measured with an electromagnetic flow probe. The portal vein, together with the lymphatics, drained freely into collection tubes. The bowel lumen was perfused at 0.85 ml/min with isotonic modified Krebs solution containing [14C]polyethylene glycol, and the luminal perfusion pressure was monitored. Luminal effluents were collected through a large-bore outlet tubing. As determined by histology, O2 consumption, vascular reactivity, and mucosal permeability, the preparations were viable for at least 60 min of perfusion. With this model, a vasoconstrictor effect of the alpha 2 adrenoceptor agonist clonidine was documented for the first time in isolated rat bowel. PMID- 1434596 TI - Preoperative radiation therapy produces an early and persistent reduction in colorectal anastomotic blood flow. AB - Preoperative external beam radiation therapy (RT) is an increasingly popular form of adjunct therapy for rectal cancer; however, little is known about its effects on healing of colorectal anastomoses. We serially evaluated colorectal anastomotic healing following moderate dose RT. Twenty-four adult female pigs were administered 4250 centiGrays (cGy) of external beam pelvic RT over 4 weeks followed by rectosigmoid resection with handsewn or circular stapled anastomosis. Groups of animals were then sacrificed at 5, 11, 60, and 120 days postoperatively. A control group (N = 24) was studied similarly but not irradiated. Perianastomotic blood flow was measured using laser doppler velocimetry at each time interval. Nonirradiated anastomoses demonstrated significantly higher blood flows compared to irradiated anastomotic segments at each study interval. In addition, early (Days 5 and 11) postoperative gross inflammatory scores and microscopic inflammatory score (all intervals) were significantly higher for irradiated animals. Anastomotic complications were more frequent in irradiated animals (7/24) vs controls (2/24, P < 0.05). These results indicate that a preoperative dose of 4250 cGy results in an early and persistent decrease in colorectal mural blood flow independent of anastomotic technique. This is the first experimental study which attempts to quantitate the effects of preoperative pelvic radiation therapy on anastomotic blood flow. PMID- 1434597 TI - The effect of temporary hepatic artery or portal vein occlusion in obstructive jaundice. AB - Hepatic hemodynamics before vascular occlusion and the effect of transient hepatic artery or portal vein occlusion on the liver were investigated in normal dogs and dogs with experimentally induced obstructive jaundice by measurement of hepatic tissue blood flow (HTBF), index of hemoglobin concentration (IHb), oxygen saturation (ISO2), serum glutamic pyruvic transaminase (SGPT) concentration, and malonaldehyde (MDA) concentration in liver tissue. Livers with obstructive jaundice had increased blood flow and a lower hemoglobin concentration compared with normal livers at baseline before vascular occlusion. Percentage change of ISO2 from baseline was higher than percentage change of HTBF after reperfusion in both normal and obstructive jaundiced liver, although they were decreased to almost similar proportions during vascular occlusion. MDA concentration in obstructive jaundice after reperfusion following vascular occlusion was higher than in normal liver. Furthermore, MDA concentration after reperfusion following hepatic artery occlusion was increased compared with after reperfusion following portal venous occlusion in obstructive jaundice. There was no evidence of massive liver necrosis which was newly developed by transient vascular occlusion. These results represent the pathological condition in the liver before transient vascular occlusion and after reperfusion in obstructive jaundice. PMID- 1434598 TI - The vascular supply of splenic autotransplants. AB - The close opposition of blood to phagocytic cells lining the pulp cords and marginal sinus has been proposed as a contributing factor in the clearance mechanism of the spleen. The vasculature of splenic autotransplants was investigated in rats using microcorrosion casts. Six-month-old splenic autotransplants and unoperated control spleens were selectively perfused and a methyl methacrylate cast was made. Scanning electron microscopy of these corroded casts was performed. In autotransplants, the marginal zone capillary network was abnormal with the fine network of capillaries replaced by dilated blood vessels. The red pulp cords were also found to be abnormal with increased diameter and loss of the fine saccular dilations found in normal spleens. The abnormally dilated capillaries and cords in the autotransplants may decrease antigen contact with these cells and hence explain previous reports of reduced phagocytic function. PMID- 1434599 TI - Limiting oxygen delivery attenuates intestinal reperfusion injury. AB - Since free radical-mediated injury is dependent on the reintroduction of oxygen into ischemic tissues, restriction of oxygen content in the initial reperfusate has therapeutic potential. The degree to which oxygen must be restricted is crucial since hypoxic injury would continue if reperfusion O2 delivery remained below the ischemic threshold of the tissue. We examined this treatment strategy in 20 pump-perfused intestinal preparations subjected to 30 min of flow interruption. The oxygen content of the reperfusate was varied by utilizing arterial (A) or venous (V) blood; as a further modification, we also performed experiments in which hemodiluted arterial blood (HD) was the reperfusate at normal (NHD) and high (HHD) flow rates. The flow rates and O2 contents of the reperfusates were adjusted to produce either high (approximately 12 ml O2/min/100 g) or low (approximately 8 ml O2/min/100 g) levels of O2 delivery. Histologic sections, obtained after ischemia and after 1 hr of reperfusion, were blindly evaluated for mucosal injury (1 = normal to 5 = severe injury). Immediately after 30 min of ischemia, all groups had comparable histologic grades (A 2.0 +/- 0.3, V 1.8 +/- 0.3, NHD 1.6 +/- 0.3, HHD 2.3 +/- 0.3). One hour after reperfusion, intestines reperfused with blood with high O2 content and hence high O2 delivery showed significantly more damage (P < 0.001) than those with exposed to low O2 delivery during reperfusion: A 3.9 +/- 0.5 and HHD 4.4 +/- 0.4 versus V 2.7 +/- 0.5 and NHD 2.9 +/- 0.3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434600 TI - Reversal of gelatin-impaired wound healing in rats by exogenous fibronectin. AB - Animal experiments have shown that administration of gelatin results in a deprivation of plasma fibronectin (FN) and impaired wound healing. For further elucidation of these findings a therapy study with purified human FN was performed in rats. Fifty animals received a standard burn injury of 1% body surface and were divided into five experimental groups. Positive controls given no further treatment or treated with solvent only served for estimation of normal healing. For a negative control, 10 animals received three intraperitoneal injections of gelatin (58 mg/kg body wt) on Days 0, 1, and 2 after injury. They exhibited a striking lack of plasma FN (Day 1) and a significant delay of wound contraction (Days 7 and 14). In the therapy groups each administration of gelatin was followed by an intraperitoneal or intracardiac injection of FN (58 mg/kg body wt) 1 hr later. In these animals the negative effect of gelatin upon plasma FN and wound contraction was prevented. According to this study wound healing is menaced by FN deficiency and can be optimized by substitution of exogenous FN. PMID- 1434601 TI - Peri-insular presence of collagenase during islet isolation procedures. AB - Reportedly, higher islet yields are obtained by ductal collagenase administration and subsequent digestion of the pancreas than by the chopped tissue collagenase digestion technique. However, the exact mechanism of islet isolation is not known. This study aims to understand the underlying mechanism of a favorable effect of ductal collagenase administration. To this end, we investigated if the higher yields can be explained by a different distribution of the collagenase enzymes in the pancreatic tissue after ductal application as compared to during chopped tissue digestion. India ink was used to mimic and visualize the distribution of collagenase in histological sections of pancreases of several species. Ink particles were seen around and even within the islets both after ductal application and during chopped tissue collagenase digestion. Thus, collagenase enzymes are not restricted to the exocrine tissue compartment with either technique. In view of this observation, we compared the efficacy of both techniques in islet isolation procedures in paired experiments in rats. Both techniques gave similar islet yields to those reportedly obtained with the ductal collagenase method. However, with either technique, the islet yield was only approximately 50% of the endocrine volume of the pancreas, indicating that a substantial loss of islet tissue had occurred. We conclude that, irrespective of the route of collagenase administration, collagenase enzymes are present in the peri-insular space during islet isolation procedures. This is pertinent in view of the finding that both methods have similar islet yields in rats and that collagenase digestion, as such, is associated with loss of islet tissue. PMID- 1434602 TI - The effects of endothelin-1 on human dermal fibroblast growth and synthetic activity. AB - Endothelin-1 (ET-1) is the most potent vasoconstricting substance known, and is believed to have a fundamental role in the regulation of blood flow. It is a peptide produced and secreted by endothelial cells in response to hypoxia and injury, as well as by macrophages. These properties suggest that ET-1 may play a role during tissue repair. In this study, we have examined the effects of ET-1 on the growth and synthetic activity of human dermal fibroblasts. ET-1 stimulated DNA synthesis in serum-deprived cultures: this effect reached a mean value of 64% more than control (P < 0.01) at 2.5 ng/ml (10(-9) M) of ET-1. In contrast, the addition of ET-1 to fibroblasts at different densities and in 0, 3, or 10% fetal bovine serum (FBS) failed to increase cell counts. In 1% FBS, a 41% mean increase in cell counts compared to control values was observed in cultures treated with 2.5 ng/ml of ET-1 (P < 0.01). Incubation of dermal fibroblast cultures at 37 degrees C for 1 hr with increasing concentrations of 125I-ET-1 resulted in saturable binding and a half-maximal specific binding of 27.5 pM. Scatchard plot analysis of the binding showed a Kd of 224 pM and 11,400 high-affinity binding sites per cell. ET-1 had no effect on [14C]-glucosamine incorporation by fibroblasts and caused no increase in collagen synthesis, as measured by collagenase-sensitive [3H]proline incorporation and by salt precipitation of 3H labeled collagen at acid and neutral pH successively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434603 TI - A simple method for bile duct anastomosis and interval bile collection in the liver-transplanted rat. AB - A mini T-tube is introduced for the bile duct anastomosis of rat liver transplantation as well as interval bile collection. The validity of the T-tube was evaluated in 14 liver-transplanted rats and compared to 14 rats using traditional stent for bile duct anastomosis. Changes of biliary tree after the T tube anastomosis were examined by T-tube cholangiography on sample rats at 4 days and at 4 months after liver grafting. Additionally, bile volumes and rates of bile salt secretion were compared in the continuously flowing cannula and the chronic T-tube fistula in normal rats. The results show that the mini T-tube facilitates bile duct anastomosis and study of bile secretion after liver transplantation in rats without increase in surgical difficulty or interference of biliary enterohepatic circulation. PMID- 1434604 TI - Implications of a pre-existing tumor hypoxic fraction on photodynamic therapy. AB - The presence of oxygen in tissue is a requirement for photodynamic therapy (PDT) induced destruction of solid tumors, otherwise no cell death occurs. Since many tumors have been shown to have significant populations of hypoxic cells, it is of clinical interest to determine if pre-existing tumor hypoxia limits phototherapy. This question was examined using RIF tumors where tumor response to PDT of completely oxygenated tumors was compared to tumors with an induced hypoxic fraction. Tumor hypoxia was induced by using vasoactive drugs (epinephrine, chlorpromazine, or isoproterenol), given 30 min prior to PDT, or by a surgical method. PDT consisted of 5 mg/kg Photofrin II ip 24 hr prior to treatment and 135 J/cm2 630-nm light. The administration of the various vasoactive agents induced hypoxic fractions of 2.2 to 10%. The surgical method induced hypoxic fractions of 35%. Tumor response and cure in animals given vasoactive agents did not differ from controls, suggesting that low levels of pre-existing tumor hypoxia do not limit photodynamic therapy in this tumor model. Animals with tumors made hypoxic by a surgical method showed significantly reduced tumor response to PDT. Only 14% of these animals had tumors which became flat and necrotic by the day following PDT, compared to nearly 100% for animals given vasoactive drugs or controls. Furthermore, no tumor cure was observed in animals treated by this method. The higher level of tumor hypoxia in these animals likely represents one point where large proportions of PDT-resistant cells can survive after treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434605 TI - Skeletal muscle fiber type does not predict sensitivity to postischemic damage. AB - Because the three distinct fiber types of skeletal muscle have significant metabolic differences, the predominant fiber type in a muscle may influence its sensitivity to injury from ischemia and reperfusion. The few studies to address this issue have been conflicting. We explored possible differences in the sensitivity of fiber types to ischemia/reperfusion injury with an isolated rat hindlimb preparation perfused with an albumin-enriched Krebs buffer. Following 120 min of ischemia and 60 min of reperfusion, the tibialis anteriorwhite, tibialis anteriorred, soleus, and plantaris muscles were assessed for injury by examining three parameters: skeletal muscle injury (via 99Tc-pyrophosphate), microvascular injury (via 125I-albumin), and tissue water content. There was no consistent correlation between fiber type and sensitivity to postischemic injury. Both the soleus (slow twitch) and plantaris (fast twitch) muscles sustained similar significant injury: muscle damage was 133 and 167% greater than controls, and microvascular damage 96 and 91% greater than controls, respectively. However, other fast twitch muscles (tibialis anteriorwhite and tibialis anteriorred) exhibited no significant injury. Both injured muscles were in the posterior compartment while the uninjured muscles were in the anterior compartment. Regional flow as measured by microspheres revealed no correlation between postischemic flow and muscle injury, microvascular injury, or compartmental location. Skeletal muscle fiber type was not consistently predictive of its sensitivity to ischemia/reperfusion-induced injury. Compartmental location may have played an as yet unknown role in modulating vulnerability to postischemic damage. PMID- 1434606 TI - Modulation of peritoneal re-epithelialization by postsurgical macrophages. AB - The studies reviewed here show that postsurgical macrophages are capable of modulating the proliferation of TRC. That is, macrophages either suppress or enhance the proliferation of TRC depending on the culture time and the medium used as a comparison, i.e., culture medium with only serum or spent medium from cultures of resident peritoneal macrophages. Postsurgical macrophages also modulate the morphology of (spindly or rounded appearance) and the secretion of extracellular matrices by TRC. The responsivity of TRC to control by postsurgical macrophage-spent media or growth factors changes as a function of postsurgical and/or culture time. In addition, cells harvested from the site of peritoneal trauma (TRC) did not respond to growth factors in a fashion entirely the same as fibroblasts. This indicates that cells harvested from the site of peritoneal injury are unique. Lastly, after removal of a suppressive factor from postsurgical macrophage-spent media by dialysis, the factors secreted by postsurgical macrophages are more potent in enhancing TRC proliferation than growth factors individually. PMID- 1434607 TI - Thoracoscopic lobectomy. PMID- 1434608 TI - Hypertension occurring for the first time postpartum: was it preeclampsia? PMID- 1434609 TI - Non-Hodgkin's lymphoma in pregnancy: a diagnostic dilemma. Case report and review of the literature. PMID- 1434610 TI - Laparoscopic evaluation of the diaphragm in penetrating injury to the lower thorax. PMID- 1434611 TI - Miscarriage in a patient with migraines. PMID- 1434612 TI - The health care crisis: causes, implications, and strategies. PMID- 1434613 TI - Recertification--a real hazard. PMID- 1434614 TI - The physician's responsibilities in dealing with organ donations. PMID- 1434615 TI - The ticking time bomb. PMID- 1434616 TI - The health care crisis. PMID- 1434617 TI - Pregnancy following Mustard operation for transposition of great arteries. PMID- 1434618 TI - Monoamniotic twin gestations. PMID- 1434619 TI - Traumatic disruption of the cervical trachea. AB - Treatment of a case of traumatic disruption of the cervical trachea has been described. This injury is not common but must be suspected in blunt chest trauma patients, with evidence of possible tracheal obstruction as in this patient. Massive subcutaneous emphysema, large air leaks, and persistent pneumothorax are more common signs of tracheobronchial disruption. Diagnosis can be made with fiberoptic bronchoscopy, and primary repair is the treatment of choice. PMID- 1434620 TI - Lead toxicity in a house painter. PMID- 1434621 TI - Newborn screening for galactosemia in Tennessee. PMID- 1434622 TI - A slow walk on a weekend. PMID- 1434623 TI - Understanding the benefits and hazards of health care reform proposals. TMA Communications and Public Service Committee. PMID- 1434624 TI - State of the art medicine outsmarted by octogenarian thumb or to dance or not to dance. PMID- 1434625 TI - Loss prevention case of the month. PMID- 1434626 TI - Life support for Medicaid. PMID- 1434627 TI - Truth in packaging. PMID- 1434628 TI - Learning alcohol tolerance by mental or physical practice. AB - Five groups of six male social drinkers learned a psychomotor task (Tracometer) and subsequently attended five sessions to perform the task after drinking. On each of the first four sessions, subjects received 0.62 g/kg alcohol. On session 5, a placebo was administered when alcohol was expected. During treatment sessions 1-3, two groups performed the task with a valuable consequence for drug compensatory performance: either information (IO) or information plus money (MI). This MI experience was mentally rehearsed by a third group (MR). Two control groups performed the task, either with no outcome (N), or with money for compensatory performance but no information about earnings until the study concluded (MO). Sessions 4 and 5 assessed the effect of the prior treatments when all groups performed the task with money and information. Groups MI, IO and MR displayed comparable and significantly more tolerance and a stronger compensatory response to placebo than control groups MO and N. The evidence indicates that mental or physical practice associating drug-compensatory performance with some valuable outcome enhances tolerance to moderate doses of alcohol. PMID- 1434629 TI - The effect of alcohol on emotional response to a social stressor. AB - Social drinkers were administered either an alcoholic, placebo or no-alcohol control beverage. Subjects were next informed that they were to give a self disclosing speech about their body and physical appearance. Subjects' heart rate and videotapes of their facial expression were recorded during this instruction. Facial reactions to the stressor were analyzed using a system based on the Maximally Discriminative Facial Coding System (Izard, 1979). Subjects who were intoxicated showed significantly less negative emotion, as measured by the facial expression analysis, than those subjects consuming either the control or placebo beverage. We attribute this effect of alcohol to its actions on subjects' appraisal of anxiety-inducing information. PMID- 1434630 TI - Neuropsychological efficiency measures in male and female alcoholics. AB - The role of time in performance on many neuropsychological tests has been relatively neglected in the literature to date. Neuropsychological functioning in 90 male and female alcoholics and 65 peer controls was examined using both accuracy and time measures for four basic types of neuropsychological functioning: verbal skills, learning and memory, problem-solving and abstracting, and perceptual-motor skills. Alcoholics had significantly lower efficiency ratios (accuracy/time) than controls in each of the four areas, and had significantly lower overall accuracy and time scores. There were no significant Group x Gender interactions for efficiency, speed or accuracy scores, indicating that male and female alcoholics have similar deficits as a result of chronic alcoholism. The study is the first to apply systematically an empirical measure of neuropsychological efficiency to different areas of cognitive function; the results have implications for neuropsychological testing procedures. PMID- 1434631 TI - The relationship between three subtypes of the flushing response and DSM-III alcohol abuse in Japanese. AB - This study examined the relationship between the flushing response and drinking patterns and DSM-III alcohol abuse among Japanese using data collected in the joint U.S.-Japan collaborative study. The flushing response was classified into the following three subtypes: typical flushing (always flushed in the face after drinking), atypical flushing (sometimes) and nonflushing (never). This study of male current drinkers showed that typical flushers drank less alcohol than did atypical and nonflushers, but there was no observed difference between the drinking patterns of atypical flushers and nonflushers. Although the relationship was less pronounced, a similar association was found for female current drinkers. The 12-month prevalence of DSM-III alcohol abuse was estimated to be highest among atypical flushers and lowest among typical flushers, with nonflushers in between for both genders. When daily alcohol consumption and other pertinent sociodemographic variables were controlled, logistic regression analyses revealed that the risk for alcohol abuse by men was approximately 3.0 times higher among atypical flushers and 1.7 times higher among nonflushers than among typical flushers. The corresponding risks for abuse by women were 7.8 (atypical flushers) and 2.8 (nonflushers) times higher. Possible explanations for these differences in drinking patterns and the risk for alcohol abuse among the three flushing subtypes and between genders are discussed. PMID- 1434632 TI - The reliability and stability of the Mortimer-Filkins test. AB - The Mortimer-Filkins test has been used widely as an instrument for detecting problem drinkers among drink-driving offenders. While extensive psychometric testing has been undertaken by the developers of the test, few independent validation studies have been conducted, and few studies have used the Mortimer Filkins test with general populations. The present study investigated the test retest and internal-consistency reliability of the instrument, and the stability of problem drinking, as measured by the instrument. The test was administered to moderate and heavy drinkers at an industrial workplace on three occasions. The results indicated that the Mortimer-Filkins test has high test-retest and internal-consistency reliability, and problem drinking, as measured by the test, appears to be a stable characteristic across time. PMID- 1434633 TI - Changing the legal minimum drinking age: results of a longitudinal study. AB - Alcohol consumption patterns of samples of college students were examined before and after legislation to raise the minimum drinking age for "weak" beer (3.2% or less alcohol content by weight). Sampling was completed just before and immediately after inception of the law, and then each semester for a total of 4 years. These samples were compared with baseline data obtained 2 years before the legislative action. Quantity and frequency of consumption showed an increase in the sampling period just before the law change and a decrease immediately following. Overall, the quantity-frequency index remained constant, and reports of problem drinking changed very little. Some adjustments were found in drinking locations with students reporting less drinking in public places, such as bars or restaurants, and more drinking in private places, such as residence halls or homes. Policy implications of legislation designed to control drinking are discussed. PMID- 1434634 TI - Problems in deterrence: a comparison of the driving histories of DUII and non DUII drivers. AB - Driving records of subjects arrested for driving under the influence of intoxicants (DUII), both recidivists and nonrecidivists, were compared with records of an age- and sex-matched random sample of non-DUII drivers. Major differences were found between DUII and non-DUII groups in the incidence of traffic violations but some differences also existed between nonrecidivist and recidivist DUII subjects. Rehabilitative diversion programs for first-time DUII offenders did not affect recidivism rates in the study population. Findings in this study suggest that general deterrence directed at the non-DUII population should receive emphasis equal to specific deterrence directed at DUII offenders. PMID- 1434635 TI - Relationship of family history, antisocial personality disorder and personality traits in young men at risk for alcoholism. AB - Studies examining possible risk factors for the development of alcoholism have focused recently on a variety of personality factors, including those associated with risk-taking behaviors. Alcohol-seeking behavior leading to the abuse of alcohol may be associated with a variety of risk-taking behaviors that derive from certain personality traits. Further, there is evidence that personality traits are transmitted across generations. This study examined the relationship of a family history of alcoholism, antisocial personality disorder (ASP) and alcohol use to several personality traits including the Tri-dimensional Personality Questionnaire (TPQ) in a sample (N = 91) of nonalcoholic, young male volunteers. The men with ASP scored higher than the non-ASP men on the Novelty Seeking Scale of the TPQ, but not on the Harm Avoidance or Reward Dependence subscales. In addition, ASP men scored higher than non-ASP men on a measure of impulsivity and tended to score higher on measures of sensation seeking, psychopathy and monotony avoidance. A family history of alcoholism did not differentiate the young men on any of the childhood behavior problems, personality measures or alcohol-related variables. PMID- 1434636 TI - A high-risk community study of paternal alcohol consumption and adolescents' psychosocial characteristics. AB - A prospective community study looked at drinking behavior and biopsychosocial correlates of adolescents (in years 9 and 10 and again in years 11 and 12 at 23 high schools) and their parents. Heavy drinkers were compared to nil/low drinkers. Sons were more likely to drink heavily if fathers drank heavily and mothers who drank heavily were more likely to cohabit with heavy drinkers. Differences in psychological characteristics and home environment were defined in regard to heavy drinking fathers and drinking sons. Difficulty in settling disagreements and reduced time spent with family were the main correlates associated with drinking by both boys who did not necessarily have a heavy drinking father and those who did. PMID- 1434637 TI - The characterization of inconsistencies in self-reports of alcohol and marijuana use in a longitudinal study of adolescents. AB - The reliability of self-reported measures remains an important issue for research on adolescent alcohol and drug use. Many studies have concluded that adolescents' self-reports are valid and reliable, but few studies have excluded consistent nonusers from their reliability estimates, and no study has examined in detail the reliability of reported age at first use of substances. This study explores the consistency of self-reports of frequency of use and age of first use of alcohol and marijuana in a sample of 5,770 secondary school students in a southeastern U.S. county. Two waves of data were collected between 1985 and 1988 using state-of-the-art data collection procedures and self-administered instruments. Consistency of reports was examined by comparing reports at T1 and T2, approximately 1 year apart. Results showed that when consistent nonusers were dropped from the analysis, consistency rates of lifetime frequency of use dropped from 82.7% to 74.7% for alcohol and from 95.6% to 83.2% for marijuana. Reports were more consistent for lifetime marijuana use than for alcohol use, but these results must be interpreted with caution given differences in the measures for the two substances. Reliability of reported age of first use was very low for both substances. When consistent nonusers were dropped from the analysis, only 27.8% of respondents made consistent estimates of their age at first alcohol use and 34.4% for their age at first marijuana use. Implications and recommendations for this area of research are discussed. PMID- 1434638 TI - The changing role of the surgeon in the management of cancer in the university setting and its impact on resident training. AB - A retrospective review was performed of 22,168 cancer cases registered by the Tumor Registry between 1965 and 1990. Eighty-six percent of these cases involved solid tumors; this number remained fairly constant throughout the study period. There was a significant trend toward more advanced disease at the time of presentation, most marked in the last 10 years; prior to 1980, 63.7% had localized or in situ cancer as opposed to only 49.4% since 1980 (P < 0.001). This suggested that more advanced cases were being submitted for treatment. As expected, more disseminated disease at the time of presentation was coupled with an overall decrease in the number of cases in which surgery comprised part of the treatment: 43.6% prior to 1980 vs. 38.1% after 1980. This trend has reversed, however, in the last 5 years. Though the number of cases in which surgery was the only treatment modality remained constant prior to and after 1985 (26.8% and 27.1%, respectively), the number of cases in which surgery was part of a multimodality treatment plan significantly increased (39.9% prior to 1985; 45.3% after 1985). This was coupled with a significant decrease in the number of cases treated with nonsurgical modalities alone (60.1% prior to 1985; 54.7% after 1985). Therefore, not only has the surgeon been called upon to operate on more advanced disease for cure in the last 5 years, but he or she has also become increasingly involved in multimodality treatment. Since 40.4% of university departments of surgery (as of 1990) did not provide specific training in surgical oncology, it is suggested that these departments reevaluate the objectives of their educational programs in view of the changing, increasingly complex role of the surgeon in the multidisciplinary approach to the care of the cancer patient. PMID- 1434639 TI - Prognostic markers of colorectal cancer: an evaluation of DNA content, epidermal growth factor receptor, and Ki-67. AB - Between January 1989 and August 1991, 62 patients undergoing resection for colorectal adenocarcinoma were assessed in a prospective fashion on the basis of various tumor characteristics that are thought to indicate prognosis. Parameters measured included epidermal growth factor receptor (EGFr) expression, a cell membrane receptor known to be overexpressed in a variety of tumors, Ki-67, a monoclonal antibody marker of cell proliferation, as well as flow cytometry and standard histologic examination. Statistical analysis included chi square with Yates correction when appropriate, Wilcoxon W, and multivariate logistic regression. EGFr positive tumors were associated with worse Dukes' stage (27% of EGFr negative tumors were Dukes' C or D vs. 58% of EGFr positive tumors, P = 0.03), as well as more aneuploid characteristics by flow cytometry (48% EGFr negative = aneuploid vs. 82% EGFr positive = aneuploid, P = 0.01). Lymphatic invasion was more frequent in EGFr positive tumors (P = 0.03). These factors proved to be independent of each other by multivariate analysis. Ki-67 did not correlate with any of the measured parameters and was of extremely limited use in the evaluation of the study population. Multivariate analysis indicated that aneuploid tumors were associated with worse Dukes' stage than diploid tumors. Histologic parameters such as lymphatic and vascular invasion as well as histologic grade are compared to the other parameters involved with prognosis. PMID- 1434640 TI - Accurate specimen preparation and examination is mandatory to detect lymph nodes and avoid understaging in colorectal cancer. AB - Lymph node involvement in colorectal cancer, one of the most important prognostic factors, can be sometimes underestimated. In this study the authors report the results of two different techniques of specimen preparation and examination. In 240 patients (Group I), histologic examination was performed using a conventional procedure. In Group II (60 cases) the resected bowel and its mesentery were separately stretched, pinned on to a cork board, and fixed. The mesentery was divided according to node location (intermediate and principal) and evaluated by sight and palpation to identify lymph nodes. The bowel segment was divided from 5 cm proximally to 5 cm distally to the tumor every 10 mm in serial 3 mm slices. Three and 10 mm slices were then carefully examined by sight and palpation. Isolated lymph nodes embedded in groups (10-12 per paraffin block) were stained and investigated for neoplastic involvement. The specimen examination procedure used in Group II resulted in identification of a higher number of lymph nodes (mean = 41.1) and nodal metastases (mean = 10) compared to the standard technique used in Group I (mean = 11.3 and 2.4, respectively--P < .05). The percentage of N+ cases also was increased in Group II (48.3%) when compared to that in Group I (30.4%; P < .05). The new technique is simple, inexpensive, and efficacious for the detection of lymphatic metastases in colorectal cancer. PMID- 1434641 TI - Prognostic assessment of superficial squamous cell carcinoma of the esophagus using karyometric analysis and nucleolar organizer regions. AB - To investigate prognostic values for squamous cell carcinoma, we measured nuclear area (NA), nuclear shape factor (NSF), DNA content and mean number of nucleolar organizer regions (NOR), using formalin-fixed, paraffin-embedded tissue sections from 39 patients with superficial squamous cell carcinoma of the esophagus. NA and DNA content were significantly higher in patients with lymph node metastasis than in those without metastasis. NA and the NOR number were also significantly higher in patients with recurrence than in those surviving for more than 3 years without recurrence. To determine the optimal combination of these parameters for prognostic assessment, we used a stepwise discriminant analysis to obtain two linear discriminant functions. One (f = 0.331 x NA + 6.64 x NSF + 9.85) gave an accuracy of 87.2% in predicting lymph node metastasis, and the other (f = -0.071 x NA - 2.34 x NOR + 13.0) yielded an overall accuracy of 88.9% in classifying patients into two groups with a better and worse prognosis. These results suggest that karyometric analysis and determination of the NOR number are useful for the prediction of disease outcome in patients with superficial squamous cell carcinoma of the esophagus. PMID- 1434642 TI - Breast masses in adolescent females. AB - In a retrospective study of 38 adolescent females operated on for mammary masses, 42 fibroadenomata (FA), 2 fibrous scars around abscesses, and one papilloma were found. All were postmenarchal. Clinical and pathological features were reviewed and the patients reexamined or interviewed. FA were mostly asymptomatic and removed a few weeks after incidental discovery. They were often seen in Jewish girls of parents born in North Africa and the Middle East, and were more frequently located in the outer superior quadrant of the left breast. New FA appeared in almost half of the cases later on in the same breast, as well as in the other breast, or bilaterally. Necrosis occurred in three FA and was unrelated to the size of the tumor. There was no correlation between the size of FA, multiplicity, or necrosis, nor between increased stromal or epithelial atypia, cellularity, or mitotic activity. One explanation for the high rate of multiplicity might be related to this neoplasm occurring in an actively developing organ under hormonal control. There was no increased breast carcinoma apparent in the family history. Therefore, except in cases of fast-growing tumors, a conservative approach is recommended because of the frequency of multiple FA as well as aesthetical postoperative complications. PMID- 1434643 TI - Colorectal carcinoma in young patients. AB - Utilizing Tumor Registry records dating from 1935 to 1988, 50 patients diagnosed with colorectal adenocarcinoma at the age of 40 years or younger were retrospectively studied with respect to sex, race, family history, delay in diagnosis, primary tumor location, tumor differentiation, mucin production, stage at presentation, and the effect of these factors on 5-year survival. This younger group of patients was compared to a computer-generated, randomly selected group of 50 patients 40 years of age or older. There was no difference with respect to sex, racial distribution, family history, symptoms at presentation, or expediency of physician diagnosis between the two groups. Younger patients waited significantly longer to seek medical attention than did their older counterparts. However, those patients who delayed presentation had no higher incidence of advanced disease than those patients who presented earlier. Younger patients had a higher incidence of poorly differentiated, advanced, right-sided tumors. This is in contrast to a predominance of well-differentiated, less advanced, rectosigmoid lesions in the older patients. There was no age-related difference in the incidence of mucin-producing tumors. Overall 5-year survival was 75% in older patients, in contrast to only 51% in younger patients (P = 0.01). We conclude in this study that it is advanced stage at presentation that is the most significant prognostic indicator in patients of all ages. The high incidence of poorly differentiated, right-sided tumors is responsible for the majority of young patients presenting with advanced disease, resulting in their poorer prognosis. PMID- 1434644 TI - Long-term right atrial catheters in patients with malignancies: an Indian experience. AB - Ninety-eight single lumen and two double lumen silicone right atrial Hickman/Broviac catheters inserted in 91 patients with various malignancies over a period of 36 months were prospectively studied. The average duration of use for all Hickman/Broviac catheters was 7,460 days with an average of 74.6 days. A total of 41 episodes of catheter-related infections were documented in all patients (0.5 per 100 access days). Catheter related bacteremia was the most frequent type of infection (31 out of 41, 75%). Majority of the bacteremias could be controlled with routine antimicrobial therapy. Exit site infections were seen in 5 Hickman/Broviac catheters. Two catheters had to be removed because of catheter tunnel infections. Gram negative bacteremic infections were the most common, with Pseudomonas aeruginosa being the major pathogen. Silicone rubber Hickman/Broviac catheters proved to be convenient, reliable, and easily manageable devices in our experience. PMID- 1434645 TI - Synergistic effects of intratumor administration of cis diamminedichloroplatinum(II) combined with local hyperthermia in melanoma bearing mice. AB - The synergistic effect of local hyperthermia (LHT) with intratumor injection (i.t.) of cis-diamminedichloroplatinum (II) (DDP) was studied using a rodent model with implanted B16 melanoma tumors. The hindfoot of the C57BL/6 mouse bearing the tumor was placed in a water bath at 42.5 +/- 0.2 degrees C (intratumor temperature was at 42.3 +/- 0.1 degrees C) for 30 minutes just after local (i.t.) or systemic (intraperitoneal;i.p.) administration of DDP (1-3 mg/kg once in experiment I and 1-3 mg/kg three times in experiment II). The tumor growth ratio (TGR) at 7 days after treatment in the group given DDP 3 mg/kg (i.t.) with LHT was 1.1 in experiment I and 0.5 in experiment II, and there was a statistically significant difference in both experiments compared to findings in other groups (P < 0.01). The mean survival time was 42.1 days in experiment I and 50.2 days in experiment II, with a significant difference in the latter (P < 0.001). Thus regional injection chemotherapy given concomitantly with local hyperthermia promotes the anticancer effects and improves the prognosis without either severe renal injury or the promotion of hematogenic metastasis. PMID- 1434646 TI - Biological monitoring of cancer chemoprevention. AB - A major limiting factor in the successful implementation of cancer chemoprevention trials has been the determination of endpoints to measure efficacy and success. The use of the ultimate goal of such trials, namely, cancer incidence, as an endpoint has serious feasibility problems, including the need for large numbers of participants, long follow-up periods, and high costs. The application of biological markers as intermediate endpoints to reveal responses to chemopreventive agents within a short time and to act as surrogates for cancer is an attractive concept worthy of intense investigation. This study reviews some potential biological markers, including genetic, cellular, biochemical, and immunological, as well as their possible application to cancer chemoprevention. PMID- 1434647 TI - Surgical treatment of colon and rectum adenocarcinoma in elderly patients. AB - The results are presented of disease-free interval and overall survival in 53 elderly patients with colon or rectum adenocarcinoma treated with curative surgery. The average age was 75.3 years (median = 75.0); 21 patients were male and 32 were female. Tumor location was as follows: rectum 18 (34%), sigmoid 17 (32.1%), right colon 14 (26.4%), and transverse colon 4 (7.5%) All patients were surgically treated following the classical patterns for tumor resection. After pathological examination, which included the histological grade differentiation, the disease stage was reevaluated following the pTNM system. Overall and disease free survival at 5 years, for all patients, independent of histological grade differentiation and disease stage, were 75.3% and 55.5%, respectively. Overall survival at 5 years for patients with grades I and II histological differentiation was 74.1% and 85.0%, respectively. None of the grade III patients (2 cases) survived more than 1 year. The 5 years disease-free survival for patients with histological grade differentiation I and II was 56.8% and 60%, respectively. There was no statistically significant difference in overall survival for patients with stages SI, SII, and SIII, but the disease-free survival at 5 years by stages was found to be significant with rates of 100%, 67.6%, and 22.6%. Postoperative mortality was 4 (7.5%). The postoperative mortality and survival rates obtained in this group of patients encourage us not to consider age as a limiting factor for curative surgical treatment. PMID- 1434648 TI - Mucinous biliary cystadenoma: a case report and review of the literature. AB - Mucinous biliary cystadenomas are rare neoplasms with protean manifestations. In most cases the mucinous material is retained within the cyst itself. We describe an asymptomatic case of a mucin secreting biliary cystadenoma in which the mucin presented as an amorphous intraluminal filling defect in the common hepatic duct on endoscopic retrograde cholangiopancreatography (ERCP). The neoplasm itself was confined to the posterior segment of the right hepatic lobe and was treated by formal right hepatic lobectomy. This case prompted a review of mucinous biliary cystadenomas. PMID- 1434649 TI - Metastatic breast carcinoma presenting as persistent diarrhea. AB - Patients with breast carcinoma metastatic to the colon generally present with multiple symptoms, usually pain, vomiting, nausea, and ascites. We describe a patient who presented only with persistent diarrhea, underwent surgery for colon cancer, and, on pathological evaluation of the surgical specimen, was found to have metastatic breast cancer affecting the colon. Metastatic breast cancer should therefore be suspected in patients with a history of breast cancer and diarrhea of unknown cause that is not accompanied by other symptoms. Evaluating such patients by colonoscopy and biopsy would provide important information relevant to choosing between colon surgery and systemic therapy. PMID- 1434650 TI - Staging invasive bladder tumors. AB - Staging of bladder tumors is based primarily on the depth of tumor invasion (T category). Stage is important to treatment planning and prognosis. The problem is that clinical evaluation by T-category alone often understages the pathologic extent of disease and does not reliably predict treatment results. The current analysis shows that the presence of a mass palpable on bimanual examination is of prognostic value. Incorporating tumor volume with microscopic tumor invasion may enhance the usefulness of clinical staging. PMID- 1434651 TI - Noncurative resection for advanced gastric cancer. AB - Between 1965 and 1985, 489 patients with advanced gastric cancer who were treated with gastric resection and in whom tumor cells remained after the operation were defined as cases of a "noncurative resection." The clinicopathological features and prognosis of these patients were examined and two groups were prepared: locally advanced cancer and cancer with a distant metastasis. In locally advanced cancer cases, tumor cells remained in the neighboring organs, lymph nodes, and/or resected margins; in those with distant metastasis, peritoneal dissemination and/or liver metastasis were present regardless of whether or not the metastasis was removed, with or without locally noncurative factors. Serosal invasion was prominent and high rates of lymph node metastasis and lymphatic involvement were evident in both groups. The survival rate for patients with locally advanced gastric cancer was better than that of patients with distant metastasis (P < 0.01). Survival time in patients with locally advanced cancer can be lengthened by resecting all of the primary tumor and as much of the metastatic lesions as possible, even if the surgical management is "noncurative." Aggressive postoperative chemotherapy for patients with distant metastasis from a gastric cancer is to be recommended. PMID- 1434652 TI - Gamma probe location of 111indium-labeled B72.3: an extension of immunoscintigraphy. AB - Eight colorectal and 5 ovarian cancer patients were evaluated with preoperative immunoscintigraphy and intraoperative gamma probe detection of 111indium-labeled monoclonal antibody B72.3. Immunoscintigraphy detected the presence of tumor in every patient shown to have tumor at surgery. There was one false-positive scan. A total of 21 pathologically verified lesions were identified at surgery in the 11 patients with tumor. Immunoscintigraphy localized 12 (57%) and intraoperative gamma probe detection located 17 (81%) of the lesions. Intraoperative probe detection located 6 of 8 lesions smaller than 1 cm and 3 lesions that were not identified on initial surgical exploration. The gamma probe offers information that is complementary to immunoscintigraphy in that (1) it aids the surgeon in locating intra- and extra-abdominal lesions previously identified by immunoscintigraphy, (2) it locates lesions too small to be seen by immunoscintigraphy alone, (3) it locates lesions that otherwise might be missed at surgery, and (4) it provides objective evidence for adequacy of surgical resection of cancer in the abdominal cavity. PMID- 1434653 TI - Clinicopathologic comparisons between estrogen receptor-positive and -negative gastric cancers. AB - We report that a modified dextran-coated charcoal (DCC) assay, including the addition of sodium molybdate and 5% DCC stripping of endogenous hormone, detected higher estrogen receptors (ERs) than those by the conventional assay. ERs in 21 gastric adenocarcinoma were determined by the modified DCC assay; 13 patients had ERs of 2.5 to 520.2 fmol/mg protein with a mean dissociation constant of 1.9 x 10(-10) M. The remaining 8 patients had no detectable amount of the receptor. There were no differences between the ER-positive and ER-negative groups in clinico-pathologic characteristics such as age, sex, tumor size, location, gross appearance, invasive depth, invasion of lymph vessel or vein of stomach wall, nodal involvement, peritoneal dissemination, liver metastasis, and curability. Histological analysis, using Japanese, Lauren's, or Ming's classifications, all revealed no differences between the ER-positive and -negative groups. The survival rate was identical for the 2 study groups. These results suggest that the presence or absence of ERs in gastric adenocarcinoma does not correlate to either biologic or clinicopathologic characteristics of this tumor; the role of ERs in human gastric cancer remains to be elucidated. PMID- 1434654 TI - Complications of radical vulvectomy and inguinal lymphadenectomy for the treatment of carcinoma of the vulva. AB - Forty-two patients with invasive carcinoma of the vulva, subjected to radical vulvectomy and inguinal lymphadenectomy, were evaluated retrospectively. The mean age of patients was 61.6 years. Fifteen patients (35.7%) had complicating medical diseases, the histopathological diagnoses were squamous carcinoma (n = 39), undifferentiated carcinoma (n = 1), and malignant melanoma (n = 2). The postoperative morbidity and mortality rates were found to be 73.8% and 11.6%, respectively. PMID- 1434655 TI - Cystic neoplasms of the pancreas: a heterogeneous disorder. AB - Cystic neoplasms of the pancreas are rare tumors with a relatively better prognosis as compared to other pancreatic cancers. They may be mistaken for pseudocysts. Seventeen patients who underwent surgical resection were analyzed. Seventy percent of the patients were females and 76.7% of the tumors were located in the tail of the pancreas. Preoperative diagnosis was made on the basis of ultrasonography and/or computed tomography findings in 60% of patients. Retrospective review of the imaging modalities revealed one or more findings suggestive of cystic neoplasms in 90% of the patients. These included multiloculated cysts, thickened cyst wall, intracystic mass or calcifications, and presence of liver metastasis. All the tumors were completely or partly excised. The final histopathological diagnosis was microcystic adenoma in 2, mucinous cyst adenoma in 1, papillary cystic neoplasm in 3, cystic neuroendocrine tumor in 5, and cystadenocarcinoma in 6. Of the 17 patients, 10 had malignant tumors. Seven patients with benign tumors and 3 patients with malignant tumors are disease free 12-30 months after resection. Cystic neoplasm must always be considered as a possibility when dealing with cystic lesions of the pancreas and a careful evaluation of ultrasonography and computed tomographic scan may give a clue to the diagnosis. PMID- 1434656 TI - Transhiatal and transthoracic esophagectomy: a comparative study. AB - From January 1981 to December 1990, 55 consecutive patients underwent esophageal resection by either the transhiatal (THE, 26 patients) or transthoracic (TTE, 29 patients) approach. Patient age, tumor size, and tumor stage were similar in the two groups. THE patients had a significantly worse mean preoperative American Society of Anesthesiologists (ASA) risk class assigned by the anesthesiologist. Patients who underwent THE had a significantly lower operative mortality and rate of cardiopulmonary complications, significantly shorter intensive care unit and hospital length of stay, and a significantly better postoperative survival when operative deaths are included in the analysis. Operative deaths in the TTE group were concentrated among patients > 65 years of age (4 of 9 died), in an ASA risk class > or = III (3 of 7 died) or with moderate or severe cardiac or pulmonary impairment preoperatively (4 of 6 died). PMID- 1434657 TI - Antitumor effect of triphenylethylene derivative (TAT-59) against human breast carcinoma xenografts in nude mice. AB - The antitumor activity of a newly synthesized triphenylethylene derivative [(E)-4 [1-[4-[2-(dimethylamino)ethoxy-phenyl]-2-(4-isopropyl)phenyl-1- butenyl] phenyl monophosphate] (TAT-59) was investigated against human breast carcinoma xenografts in nude mice with reference to the changes of hormone receptors. Five strains (MCF-7, Br-10, R-27, ZR-75-1, and T-61) used for the experiments possessed cytosol estrogen receptor (ER), and their growth was estradiol dependent. Five mg of TAT-59 and tamoxifen citrate (TAM) per kg were administered p.o. daily except Sunday. TAT-59 showed a positive antitumor effect against MCF-7 and R-27, whereas TAM was effective on MCF-7, and their adverse effects detected by mortality rate, body weight loss, and spleen weight loss were similar to each other. The reduction of ER and production of progesterone receptor (PgR) after the treatment with TAT-59 were more potent than after TAM, suggesting that TAT-59 exerts its antitumor effect through binding to ER. These findings suggest that TAT-59 might merit use in clinical trials with breast cancers. PMID- 1434658 TI - Management of long-term postirradiation periclavicular complications. AB - Four cases of periclavicular postirradiation sarcoma and two cases of clavicular osteoradionecrosis with pathologic fractures are reported. All six cases presented more than 10 years after irradiation for breast cancer (five) or nasopharyngeal carcinoma (one). A review of radiotherapy received showed that they were subjected to unconventional radiation schedules (hypofractionation or high dose per fraction treatment). An approach to diagnosis and management of periclavicular lesions arising long after therapeutic irradiation is presented and the unique problems encountered with periclavicular surgery are discussed. PMID- 1434659 TI - Early drain removal following modified radical mastectomy: a randomized trial. AB - The dilemma of increasing costs of medical care and shrinking health budgets has stimulated attempts to implement stricter control on expenditure without affecting the quality of care. This study shows that in patients with operable breast cancer, a policy of early discharge after a mastectomy did not have deleterious effects on wound healing and was well accepted by patients. In a randomized trial, drains were removed after either 3 or 6 days postmastectomy, and in both groups of patients there was no difference between the mean volumes of seromas aspirated or the number of aspirations and return visits to the hospital. This suggests that a policy of early discharge is safe, acceptable, economical, and may improve bed utilization. PMID- 1434660 TI - Primary gastrointestinal lymphomas in Turkey: a retrospective analysis of clinical features and results of treatment. AB - Thirty-three patients with primary gastrointestinal lymphoma (GIL) followed at Ankara University Medical School have been evaluated. The most frequent locations of the disease are the small intestine (48.4%) and the stomach (39.3%). The intermediate and high grade lymphomas constitute 84.8% of the cases. The mean age of the patients with small intestinal lymphoma is 28.7 years and 47.1 years for those with gastric lymphoma. The patients treated with surgery and chemotherapy (S+CT) have a longer survival than those treated with chemotherapy (CT) alone. IN CONCLUSION: 1) Small intestinal lymphoma occurs more frequently than gastric lymphoma in our study. 2) The median age of the Turkish patients with primary GIL is approximately 10 years less than those in the Western countries. 3) The therapeutic results of S+CT are superior to those of CT in the early stages of the disease. PMID- 1434662 TI - The effect of vagotomy and pyloroplasty on colorectal tumor induction in the rat. AB - Epidemiologic studies have suggested that vagotomy increases subsequent colorectal cancer risk. This hypothesis was investigated in the rat 1,2 dimethylhydrazine (DMH) colorectal carcinogenesis model. Eighty-five rats were divided into four groups having either truncal vagotomy and Heineke-Mickulicz pyloroplasty, pyloroplasty alone, laparotomy alone, and anesthesia alone. After recovery from the procedures, colon tumors were induced with five injections of DMH. Results of carcinogenesis show a trend towards increased incidence and yield of colorectal and duodenal tumors after vagotomy, though this was not statistically significant, perhaps because the high postoperative mortality from vagotomy diminished the power of the study. PMID- 1434661 TI - Experimental chemotherapy for xenograft cell lines of human bile duct and gall bladder cancers in nude mice. AB - Most biliary tract cancers are advanced and inoperable when first diagnosed. Even if surgery can be performed, the postsurgical prognosis of these diseases is poor. In the present study, we investigated effective chemotherapies for a human bile duct cancer xenograft cell line (undifferentiated carcinoma, BDC-SN) and a gall bladder cancer xenograft cell line (well-differentiated adenocarcinoma, GBC GN), which were transplanted into nude mice. Eight anticancer agents (CDDP, 5-FU, VDS, MMC, ADR, EPIR, CQ, and VP-16) and their various combinations were evaluated at 2-4 times the clinical dose. When used singly, CDDP, 5-FU, and VDS were effective against BDC-SN, and only CDDP was effective against GBC-GN. Among the various 2-agent combinations, CDDP + 5-FU was the most effective against both BDC SN and GBC-GN. However, 3-agent combinations consisting of CDDP + 5-FU + another agent were less effective than the CDDP + 5-FU double regimen and caused significant loss of weight as well as high mortality. These results suggest that CDDP + 5-FU may be the most useful regimen against biliary tract cancers in clinical application. PMID- 1434663 TI - Bowel perforation due to metastatic lung cancer. AB - Lung cancer infrequently metastasizes to the bowel. When this occurs, the symptoms may vary from mild to emergent in nature. Three patients are presented illustrating the life threatening complications that may occur due to bowel metastases of lung carcinoma. A review of the literature reveals that only four of 24 reported patients have survived bowel perforation due to metastatic lung carcinoma. One of the three patients presented herein survived to be discharged home. Patients with known lung carcinoma who develop abdominal complaints should be investigated aggressively to prevent life-threatening complications by early intervention. PMID- 1434664 TI - A method for investigating hepatocyte polyploidization kinetics during postnatal development in mammals. AB - A method for investigating weakly-proliferating cell populations of liver parenchyma on the basis of a quantitative analysis of hepatocyte polyploidization during postnatal development is described. The method uses a mathematical model which characterizes the hepatocyte polyploidization process, and incorporates data concerning the time course for relative frequencies of hepatocytes in different ploidy classes. As a result of these measurements and calculations for rat liver, transition rates of hepatocytes (the relative number of cells during a given time unit) from one ploidy class to another, and a coefficient for the reduction of hepatocyte mitotic activity with an increase in its ploidy class were obtained. Calculated curves show a good correspondence with the real process of hepatocyte frequency changes as they relate to changes in the age of the animals. To check this method, experiments investigating time changes of autoradiographic label content in the different ploidy classes of hepatocytes were carried out. By mathematically modeling the label diluting process resulting from cell proliferation and polyploidization, transition rates of hepatocytes were calculated, and they reflect values calculated from the model according to changes in occurrence frequencies. PMID- 1434665 TI - Phenotypic evolution under gene-culture transmission in structured populations. AB - I consider a simple model for the evolution of a quantitative character is structured populations when an offspring's phenotype is determined partly by his or her genetic constitution and partly by cultural transmission of the parental phenotype. Analysis of the model indicates that when individual and group selection are in the same direction, phenotypic evolution always proceeds faster under gene-culture vs. purely genetic transmission. When individual and group selection are countervailing, altruistic characters evolve faster under gene culture transmission when individual selection is weak and migration among groups is limited, with increased individual selection and migration tending to decrease the advantage of gene-culture transmission over purely genetic transmission. Given the prevalence of cultural transmission in higher species, these results suggest that contrary to what is often assumed, group selection may indeed by a potent evolutionary force in the evolution of altruistic characters. PMID- 1434666 TI - Intragenomic conflict and the evolution of eusociality. PMID- 1434667 TI - Sodium-calcium exchange: derivation of a state diagram and rate constants from experimental data. AB - A mechanism is developed for Na(+)-Ca2+ exchange using a new approach made possible by the availability of computer software that allows the systematic search of a large parameter space for optimum sets of parameters to fit multiple sets of experimental data. The approach was to make the experimental data dictate the form of the mechanism: the qualitative features of the data dictating the number and nature of the states of the exchanger and their interrelationship, and the quantitative aspects of the data dictating the values of the rate constants that govern the amount of each state relative to the total amount of exchanger. A single set of experimental data served this initial purpose, namely, observations of equilibrium Ca(2+)-Ca2+ exchange in cardiac sarcolemmal vesicles (Slaughter et al., 1983, J. biol. Chem. 258, 3183-3190). From this data a minimum mechanism was induced having 56 states (SYM56), which gave satisfactory quantitative fits to the experimental data. With this set of parameters additional experimental data were fitted, from the same preparation, the single cardiac cell and the squid giant axon, with some changes in parameters, but none dramatic. In spite of the symmetric nature of the mechanism, i.e. binding constants for Na+ and Ca2+ do not depend on the orientation of the binding sites, the mechanism exhibits marked asymmetric behavior similar to that observed experimentally. Finally, in accounting for Ca(2+)-Ca2+ exchange in the absence of monovalent cations, Ca2+ influx becomes dependent on intracellular Ca(2+)--an unexpected outcome--exactly in keeping with the "essential activator" role of intracellular Ca2+ observed by DiPolo & Beauge (1987, J. gen. Physiol. 90, 505-525). Observations of Na(+)-Ca2+ exchange in the retinal rod outer segment are well fitted with a simplified version of SYM56 comprising 25 states (namely, SYM25), supporting the notion that the exchanger in the retinal rod outer segment differs from that in cardiac sarcolemma and squid axon. Maximum turnover rate of 840 sec-1 for SYM56 and 20 sec-1 for SYM25 are comparable to those reported for the exchanger in cardiac muscle and retinal rod outer segment, respectively. PMID- 1434668 TI - The growth of mammals following a period of nutritional limitation. AB - A theory of predicting the growth of an animal following a period of nutritional limitation is proposed here. The theory consists of the following three propositions. Proposition 1: there is a scale of size, such that the growth rate following a period of nutritional limitation is that of normal animals at the same size. Proposition 2: any abnormalities in body composition at the end of the period of limitation will be corrected over time. Proposition 3: the rates at which abnormalities in body composition at the end of the period of limiting conditions are corrected, are always set by the conditions of rehabilitation. The propositions are connected with three other problems viz normal growth, growth under some limitation and the conditions needed by an animal to perform at its potential. These problems are dealt here by: (i) using a simple description of normal growth, (ii) considering the limitation by its effects rather by attempting to predict the effects of a given limitation, and (iii) using simple assumptions about protein and energy scales and requirements. The predictions of the theory are compared with experimental data, and a good qualitative agreement is found. Important conclusions from the theory are: (a) that it is essential to measure as fully as may be the state of the animal at the end of the period of limitation and to compare it with the state of normal animals and (b) that careful attention needs to be given to the choice and the description of the treatment, or preferably treatments, during the rehabilitation period. PMID- 1434669 TI - A mathematical model of homologous recombination in cultured cells. AB - This work presents a model describing the rate of recombination between homologous segments of DNA stably integrated into the genome of cultured cells. The model has been applied to rat cell lines carrying the polyomavirus middle T oncogene and a functional origin of viral DNA replication. Introduction of the gene coding for the polyoma large T antigen or the SV40 large T antigen into cells by DNA transfection promotes homologous recombination in the resident viral inserts with rates varying between 0.1 x 10(-3) and 3.7 x 10(-1) per cell generation. PMID- 1434671 TI - Promotion of evolution: disparity in the frequency of strand-specific misreading between the lagging and leading DNA strands enhances disproportionate accumulation of mutations. PMID- 1434670 TI - Applied molecular evolution. PMID- 1434672 TI - A stochastic evolutionary model of molecular sequences. AB - A stochastic evolutionary model of molecular sequences is proposed. The basic forces in evolution are supposed to be mutation and selection. The concept is somewhat similar to Kauffman-Levin's concept of adaptive walks and corresponding analytical expressions have been developed. The selective force is divided into two parts: a slowly-varying part and a rapidly-changing fluctuation. The latter influences the distribution of sequences and results in an equation of motion along the flow line. The former plays a more important role in the emergence of evolutionary order. It is demonstrated that the asymmetry of selective forces would lead to a definite order of the system. PMID- 1434673 TI - Intron evolution: a statistical comparison of two models. AB - The two most frequently occurring explanations for the existence and distribution of introns in the genes of different species are: (1) introns are remnants of the original genetic material. (2) Introns were introduced during evolution. We construct mathematical models corresponding to these two explanations, and calculate the probabilities that the intron distribution in genes from different species coding for actin, alpha-tubulin, triosephosphate isomerase and superoxide dismutase are described by these models. In both models, the branch lengths as well as the structure of the corresponding evolutionary tree is taken into account. Every branch in the evolutionary tree is assumed to have its own individual rate of loss of introns for the first model and rate of gain of introns for the second model. These rate constants are estimated from the actual number of introns. Using the rate constants we stimulate the intron evolution and calculate the probabilities that the actual intron arrangements are produced. The results for actin and alpha-tubulin, which are the two genes we have the most data for, favor the model corresponding conjecture (1), i.e. the idea that introns are old. This contradicts the results from an earlier attempt to model intron evolution where almost the same data was used (Dibb & Newman, 1989, EMBO J. 8, 2015-2021). PMID- 1434674 TI - A comprehensive multiple matrix model representing the life cycle of the tick that transmits the agent of Lyme disease. AB - An extension of Leslie matrix methodology was developed to describe the life cycle of Ixodes dammini, the tick that transmits the agent of Lyme disease in eastern North America. Thereby, we described the seasonally changing pattern of interactions of the tick with its various hosts in a well-studied site on Nantucket Island, Massachusetts. Particular numerical values representing the site were estimated mainly on the basis of published values and interpreted on the basis of experience. The model was used to predict seasonal abundance and annual rate of increase of this vector tick. Although these ticks quest for hosts during two consecutive feeding seasons, all but a few feed during the first such season. The relative distribution of developmental stages of the tick stabilized after 35 years. Abundance of the simulated population increased exponentially and doubled every 6 years. The simulations produced realistic seasonal feeding distributions of the ticks in its various developmental stages. PMID- 1434675 TI - Evolutionarily stable age at first reproduction in a density-dependent model. AB - We develop a new model of life history evolution to investigate the evolution of age at first reproduction. Density dependence is taken into account. For a given "species", age of maturity, offspring survival, immature survival, adult survival, fecundity, immature age-classes entering in competition with adults and immature competitive ability are traits adjustable by natural selection, and constitute a particular strategy. On the contrary, the type of intraspecific competition (scramble or contest), strength of competition and inherent net reproductive rate Ro(inh) are fixed (specific) characteristics. As a consequence of fixing Ro(inh), the evolution of any trait will affect trade-offs between others. Evolutionarily stable strategies are determined numerically by using the mathematical concept of Lyapunov exponents. Altogether, we consider 960 different hypothetical "species" (i.e. different combinations of fixed traits). Corresponding ESSs are analyzed with respect to their age at first reproduction, adult survival and immature competitive ability components. They appear to be gathered in three groups. One is intuitive and characterized by a reduction of immature competitive ability and a correlation of age of maturity with adult survival; populations reach mainly equilibria. The two other groups respectively include "species" with low age of maturity but high adult survival, and "species" close to semelparity with delayed maturity; immature competitive ability may not be minimized, and populations possibly exhibit complex dynamics. In conclusion, the hypothesis that the evolution of a demographic parameter modifies trade-offs between others turns out to have important consequences. We argue that life history theory cannot ignore the source and mode-of-operation of density dependence and must regard potential short-term instability as essential. PMID- 1434676 TI - South African traditional herbal medicines used during pregnancy and childbirth. AB - Many black South African women use traditional herbal remedies as antenatal medications or to induce or augment labour. Very little is known about the pharmacology and potential toxicity of the plants used in these herbal remedies. The ethnic background and traditional usage of these remedies was researched and a literature survey revealed that 57 different plants were used in herbal remedies during pregnancy and childbirth. Several of these plants are poisonous and details of their toxicity are given. PMID- 1434677 TI - Headache treatments by native peoples of the Ecuadorian Amazon: a preliminary cross-disciplinary assessment. AB - Headache, specifically migraine, is an extremely frequent and debilitating syndrome with worldwide prevalence, including indigenous cultures of Amazonia. This paper considers headache as perceived within the medical philosophy of 5 Indian tribes of the Ecuadorian Amazon Basin. Their ethnobotanical treatments for headache are examined, along with the limited available biochemical assay data. This information is analyzed by means of an Ethnopharmacology Rating Scale. Suggestions are offered as to methods of biochemical analysis that may be fruitful in assessment of potential clinical headache remedies. Key among these is the screening of ethnobotanical samples for serotonin receptor activity. The potential may exist for the discovery of more effective, less toxic headache drugs, as well as for the development of a new industry for the local economy that could promote conservation of an endangered ecosystem. PMID- 1434678 TI - Essential oils and antimicrobial activity of two varieties of Cedronella canariensis (L.) W. et B. AB - The qualitative and quantitative determination of the essential oils of the aerial part of two varieties of Cedronella canariensis (L.) W. et B., namely, C. canariensis var. canariensis and C. canariensis var. anisata have been performed, together with the study of the antimicrobial activity of both oils. The noteworthy inhibition exhibited against Bordetella bronchiseptica and Cryptococcus albidus may justify the popular use of the these plants in the treatment of certain diseases of the respiratory tract. PMID- 1434679 TI - Stevioside effect on renal function of normal and hypertensive rats. AB - Physiological and pharmacological experiments have suggested that stevioside from the leaves of Stevia rebaudiana acts as a typical systemic vasodilator. The effect of stevioside on renal function in both normal and with experimental renal hypertension rats (GII) was evaluated using clearance techniques. Stevioside provoked hypotension, diuresis and natriuresis in both the normal and hypertensive rats. Normal rats presented an increase in renal plasma flow (RPF) and glomerular filtration rate (GFR) constant following stevioside administration. The last effect is in part due to vasodilation of both the afferent and efferent arterioles. Moreover, stevioside infusion in hypertensive rats caused an increase in RPF and GFR. These data are consistent with impairment of a renal autoregulation mechanism in this experimental hypertensive model. PMID- 1434680 TI - Cardiovascular responses in the normotensive rat produced by intravenous injection of gambirine isolated from Uncaria callophylla B1. ex Korth. AB - Among several alkaloids, including dimeric indoles, isolated from Uncaria callophylla, gambirine which is an alkaloid unique to this plant, has been found to be another hypotensive principle from the plant. Intravenous injections of gambirine in the dose range of 0.2 to 10.0 mg/kg caused a dose-related fall in both systolic and diastolic blood pressures as well as heart rate. At all doses gambirine showed a prompt onset of action and at the higher doses (5.0-10 mg/kg), marked persistence of hypotension accompanied by severe bradycardia were observed. In addition, higher doses of gambirine produced a more marked decrease in diastolic than systolic pressure while at lower doses both decreased equally. It is suggested that the hypotensive effect of gambirine may be peripheral in origin and is associated, at least in part, with a cardiac action. PMID- 1434681 TI - Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedies (Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus). AB - Herbal remedies are widely used in Vietnam alongside modern drugs. We assessed the diuretic effect of four traditional Vietnamese herbal remedies from Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus, all claimed to produce an increase of diuresis. No influence was recorded for the 12- and 24-h urine output or on the sodium excretion for any of the drugs when tested under standardized conditions in a placebo controlled double-blind crossover model. The present study indicates the need for critical review of the present recommendations regarding therapy with plant materials in countries relying on empiric traditions. PMID- 1434682 TI - Pharmacologic properties of Moringa oleifera. 2: Screening for antispasmodic, antiinflammatory and diuretic activity. AB - Hot water infusions of flowers, leaves, roots, seeds and stalks or bark of Moringa oleifera were screened to detect three pharmacologic activities in experimental models in rats. The antispasmodic activity was demonstrated using isolated duodenum, oral anti-inflammatory activity by carrageenan-induced hindpaw edema and oral diuretic activity by urine output in metabolic cages. The seed infusion showed a significant inhibition of acetylcholine-induced contraction with an ED50 of 65.6 mg/ml bath concentration, inhibition of carrageenan-induced edema at 1000 mg/kg and diuretic activity at 1000 mg/kg. Some activity was also demonstrated in the roots. All doses expressed here are as equivalents of dried starting plant material. PMID- 1434683 TI - Evaluation of xanthotoxol for central nervous system activity. AB - Xanthotoxol (XT), 8-hydroxypsoralen, exhibited dose-graded sedative activity in dogs, cats, rats, mice and hamsters. At doses of 5-20 mg/kg intraperitoneally (i.p.) in cats and 3-100 mg/kg orally (p.o.) in dogs, XT blocked predatory mouse/rat killing behavior. In mice, XT (10-300 mg/kg i.p.) exhibited a dose dependent reduction in locomotor activity but was less potent in this regard than reference diazepam (10-100 mg/kg i.p.). XT in mice (0.1-10.0 mg/kg i.p.) and in hamsters (0.1-10.0 mg/kg p.o.) antagonized amphetamine-induced hypermobility but was less potent than diazepam. XT elevated the electrical threshold in foot-shock induced fighting behavior in rats. XT (0.1-30.0 mg/kg p.o.) potentiated pentobarbital-induced narcosis in hamsters at otherwise subeffective doses of pentobarbital. Conditioned avoidance responses in rats were not significantly altered with 1-3 mg/kg i.p. and 30-100 mg/kg p.o. doses of XT but 300 mg/kg p.o. blocked both conditioned and unconditioned response. Doses of 100-1000 mg/kg i.p. of XT in mice were used to study 48-h acute toxicity of XT and its LD50 was estimated to be 468 mg/kg. Doses of 10, 40 and 80 mg/kg p.o. were used to study the chronic toxicity of XT in rats for 6 months and no side effects or abnormalities in reproductive activity or endocrine integrity were noted. The F1 generation of rats from 6-month XT-treated parents were free of teratogenic effects. PMID- 1434684 TI - Phytochemical and analgesic investigation of Tabebuia chrysotricha. PMID- 1434685 TI - Anti-granuloma activity of Iraqi Withania somnifera. AB - The granuloma-tissue formation inhibiting activity of various fractions of an extract of the aerial parts of Withania somnifera were established using subcutaneous cotton-pellet implantation in rats. Antiinflammatory activity was retained in the methanolic fractions of the plant extract and was comparable to that of a 5 mg/kg dose of hydrocortisone sodium succinate. Activity was attributed to the high content of biologically active steroids in the plant, of which withaferin A is known to be a major component. PMID- 1434686 TI - Medicinal plants used to treat malaria in Madagascar. AB - Two-hundred thirty-nine Madagascan medicinal plants have been either retrieved from computerized ethnobotany information or identified in our own ethnomedicine work as having antimalarial properties. Such a high rate percent of plants compared to those used empirically to treat other diseases reflects the importance and the complication of this major tropical disease in Madagascar. PMID- 1434687 TI - The Moraceae-based dart poisons of South America. Cardiac glycosides of Maquira and Naucleopsis species. AB - The use of cardenolide-containing Moraceae in the dart poisons of South America is reviewed. Those prepared by the Choco Indians of western Colombia--called niaara or kieratchi--have probably been made from the latex of Naucleopsis amara and N. glabra. In Ecuador, the Colorado Indians used N. chiguila, while the Coaiquer Indians still derive a poison from the latex of N. naga and the Cayapa Indians occasionally make use of a blowgun poison, hambi, which probably also comes from a Naucleopsis species. The Kabori (Rio Uneiuxi Maku) Indians of north western Brazil may have utilized Maquira coriacea, but a more recent collection documents N. mello-barretoi latex as a source of their poison. The Tikuna Indians of western Brazil included leaves and bark of N. stipularis in one of their poisons. The principal cardiac glycosides present in Maquira species are strophanthidin-based and the main ones occurring in Naucleopsis species are antiarigenin- as well as strophanthidin-based. The structures of two new glycosides, isolated from dart-poison samples, have been established as strophanthidin beta-D-glucomethylosido-D-alloside and beta-D-digitoxosido-D alloside. The former is a major component of pakurin, the crystalline glycoside mixture prepared by Santesson in 1928 from a Choco Indian poison. PMID- 1434689 TI - Inhibition of Microlax-induced experimental diarrhoea with narcotic-like extracts of Psidium guajava leaf in rats. AB - Measurement of rates of propulsion in the small intestine in control and experimental groups of male Sprague-Dawley rats (200-250 g) were carried out as a means of assessing antidiarrhoeal activity of aqueous extracts of the leaf of Psidium guajava (L.), using morphine as the standard drug of reference. Hyperpropulsion (diarrhoea) was induced by gavaging rats in a control group with Microlax, using phenol red mixed into it as a marker in the intestine, and the mean rate of the hyperpropulsion was determined. The normal rate of propulsion, defined as the percentage of the length of the ileum traversed by the front of the dye in 1 h after gavaging animals with a liquid paraffin-phenol red meal, was also determined in another control group. In experimental groups pretreated with enteral administration of either morphine or aqueous extracts, 1 h before the challenge with Microlax, the percentage inhibition to the hyperpropulsive rate (antidiarrhoeal activity) was calculated. Both morphine and the extracts produced a dose-response relationship in their antidiarrhoeal effects. A dose of 0.2 ml/kg fresh leaf extract produced 65% inhibition of propulsion. This dose is equiactive with 0.2 mg/kg of morphine sulphate. The antidiarrhoeal action of the extract may be due, in part, to the inhibition of the increased watery secretions that occur commonly in all acute diarrhoeal diseases and cholera. PMID- 1434688 TI - Experimental cardiovascular depressant effects of garlic (Allium sativum) dialysate. AB - The objectives of this work were to investigate the effects of a garlic dialysate on diastolic blood pressure (DBP), heart rate (HR) and electrocardiogram (ECG) of anaesthetized dogs and its effects on frequency and tension of isolated rat atria. Garlic dialysate led to a drop in DBP (from 112.5 +/- 3.67 to 70 +/- 3.16 mmHg) and a decrease in HR (from 198 +/- 9.81 to 164 +/- 16.59 beats/min) in a dose-dependent manner. The ECG showed a regular sinus bradycardic rhythm. The addition of garlic dialysate to isolated left rat atria evoked a decrease in tension development. Frequency, measured by spontaneous beating of the right atria, was also reduced. Both effects were dose-dependent. In addition to these effects, the positive inotropism and chronotropism induced by addition of isoproterenol 10(-9) M, were partially antagonized by preincubation of the rat atria with the garlic dialysate. The above findings can be explained by a depressant effect on automaticity and tension development in the heart, suggesting a beta-adrenoceptor blocking action produced by the garlic dialysate. PMID- 1434690 TI - Biological and chemical studies of Pera benensis, a Bolivian plant used in folk medicine as a treatment of cutaneous leishmaniasis. AB - The stem barks of Pera benensis are employed by the Chimane Indians in the Bolivian Amazonia as treatment of cutaneous leishmaniasis caused by the protozoan Leishmania braziliensis. The chloroform extracts containing quinones were found active against the promastigote forms of Leishmania and the epimastigote forms of Trypanosoma cruzi at 10 micrograms ml-1. The activity guided fractionation of the extract by chromatography afforded active compounds. Their structures were elucidated, by spectral and chemical studies, as known naphthoquinones, plumbagin, 3,3'-biplumbagin, 8-8'-biplumbagin, and triterpene, lupeol. The activity in vitro of each compound was evaluated against 5 strains of Leishmania (promastigote), 6 strains of Trypanosoma cruzi (epimastigote) and the intracellular form (amastigote) of Leishmania amazonensis. The baseline drugs used were Glucantime and pentamidine (Leishmania spp.), nifurtimox and benznidazole (T. cruzi). Plumbagin was the most active compound in vitro. This study has demonstrated that Pera benensis, a medicinal plant used in folk medicine, is an efficient treatment of cutaneous leishmaniasis. PMID- 1434691 TI - Medicinal plants used by the Fang traditional healers in Equatorial Guinea. AB - This work is an ethnobotanical study of some medicinal plants used by the Fang traditional healers of two regions of Equatorial Guinea in Central Africa: Malabo and Bata. For each species listed, the family, the botanical name, the voucher specimen number, the vernacular name, the pharmacological and therapeutical properties are given. PMID- 1434692 TI - An Ayurvedic formulation 'Trikatu' and its constituents. AB - 'Trikatu' is an Ayurvedic preparation containing black pepper, long pepper and ginger, which is prescribed routinely for a variety of diseases as part of a multidrug prescription. These herbs along with piperine (alkaloid of peppers) have been shown to possess diverse biological activities in mammalian systems. A review is presented of these studies and it has been suggested that their use in the Indian system of medicine could be due to their bioavailability enhancing action on other medicaments. PMID- 1434693 TI - Inventory of plants used in traditional medicine in Somalia. III. Plants of the families Lauraceae-Papilionaceae. AB - Thirty-five plants are listed, which are used by traditional healers in the central and southern parts of Somalia. For each species are listed: the botanical name with synonyms, collection number, vernacular name, medicinal use, preparation of remedy and dosage. Results of a literature survey are also reported including medicinal use, substances isolated and pharmacological effects. PMID- 1434694 TI - The Association at seventy-five: the challenge of the future. PMID- 1434695 TI - Operative treatment of Ebstein's anomaly. AB - From April 1972 to February 12, 1991, 189 patients with Ebstein's anomaly underwent repair. Ages ranged from 11 months to 64 years (median 16 years, mean 19.1 years). In 58.2%, tricuspid valve reconstruction was possible, and in 36.5%, a prosthetic valve, usually a bioprosthesis, was inserted. In 5.3%, a modified Fontan or other procedure was performed. There were 12 hospital deaths (6.3%). All 28 patients who had accessory conduction pathways (Wolff-Parkinson-White syndrome) underwent successful ablation of the pathways as part of the operative treatment. Follow-up was obtained in 151 (85.3%) patients. Of those patients followed up more than 1 year after operation, 92.9% were in New York Heart Association class I or II. There were 10 late deaths: seven cardiac (four sudden), two noncardiac, and one of an unknown cause. Postoperative Doppler echocardiographic assessment showed the atrial septum was intact in all patients and tricuspid valve function was good to excellent in most patients. Four of the 110 patients (3.6%) who underwent valve reconstruction required reoperation 1.4 to 14.1 years later. Postoperative reduction in heart size was usual, atrial arrhythmias were reduced, and late postoperative exercise testing showed a significant improvement in performance: Maximal oxygen consumption increased from a mean of 47% of predicted value before the operation to a mean of 72% after the operation. Nine patients had a total of 12 successful pregnancies with deliveries of normal children. PMID- 1434696 TI - Morphology of ventricular septal defects in complete transposition. Surgical implications. AB - Postmortem examination of 62 hearts with complete transposition (concordant atrioventricular and discordant ventriculoarterial connections) and an accompanying ventricular septal defect was performed to determine the morphologic variability of ventricular septal defects and to explore the surgical implications of these defects. Particular attention was directed toward assessing alignment of the outlet septum relative to the muscular septum. Coronary arterial distributions were also evaluated, but specific patterns of distribution did not correlate with morphology of the defect. Of 49 hearts with a normally aligned outlet septum, there were 24 perimembranous, 21 muscular, and 2 doubly committed and juxtaarterial defects. Two hearts had both perimembranous and muscular defects. Twelve of the 21 muscular defects were "central," being surrounded entirely by muscle and located just below the leaflets of the pulmonary valve, and 9 were located in the inlet or apical trabecular septum. There were 13 hearts with malalignment of the outlet septum, anteriorly in 11 and posteriorly in 2. All with anterior malalignment had a subpulmonary defect that was perimembranous in 7 and muscular in 4. Both defects with posterior malalignment had a subaortic perimembranous defect. Because variations in morphology of a ventricular septal defect have a direct impact on selection of the most suitable surgical repair, specific operative approaches are discussed. PMID- 1434697 TI - Role of the septal leaflet in tricuspid valve closure. Consideration for treatment of complete atrioventricular canal. AB - A septal leaflet of the tricuspid valve is thought to work differently from other anterior and posterior leaflets. We studied its role in valve closure in dogs by means of a dynamic area meter. During the control state, the tricuspid valve orifice area increased twice in diastole coincidentally with either atrial systole or rapid ventricular filling. We observed several findings after the septal leaflet resection: (1) two peak area patterns of the tricuspid valve orifice in diastole, (2) no elevation of right atrial pressure on ventricular systole (there was no V wave), (3) no tricuspid valve regurgitation on right ventriculography. These findings suggest that a complete valve closure occurred without the septal leaflet in regular sinus rhythm. An elevation of the right ventricular pressure produced by pulmonary artery stenosis without septal leaflet, however, easily caused tricuspid valve regurgitation in contrast to the same pressure of the right ventricle with the normal tricuspid valve. The right ventricular pacing caused severe valve regurgitation without the septal leaflet. Results indicate that in the repair of the complete atrioventricular canal defect and other tricuspid valve lesions, the septal leaflet of the tricuspid valve rarely requires attention. An atrioventricular block should be avoided, however, because electrical cardiac pacing on the right ventricle causes severe valve regurgitation without the septal leaflet. PMID- 1434698 TI - The Mustard procedure for correction of simple transposition of the great arteries before 1 month of age. AB - Since April 1976, 34 infants (25 male and 9 female) less than 1 month of age underwent a Mustard intraatrial baffle procedure for repair of simple transposition of the great arteries. Thirty patients were less than 2 weeks old and 19 patients less than 1 week (mean 7.8 +/- 6 days). The weights ranged from 2.6 to 4.4 kg (mean 3.4 +/- 0.4 kg). Rashkind balloon atrial septostomy was performed in the first hours or days of life in 29 patients. The average interval from balloon atrial septostomy to baffle repair was 3.9 days (range 2 hours to 14 days). Mechanical ventilation was required in eight patients preoperatively and prostaglandin E1 was infused in 17 patients to maintain ductal patency. In all patients, the Mustard procedure was performed with the use of deep hypothermic circulatory arrest, averaging 53 minutes (range 37 to 82 minutes). The duration of postoperative intubation and ventilatory support averaged 1.7 +/- 1.0 days (range 1 to 5 days). Inotropic drugs were used in 24 patients during a period of 1.4 +/- 1.3 days (range 1 to 6 days) postoperatively. There were no hospital deaths. Follow-up evaluation has extended from 1 month to 14 years (mean 3 +/- 3 years). One infant died 2 months postoperatively as a result of milk aspiration; no cardiac defects were found at the autopsy. A second infant died at 1 year with right ventricular and tricuspid valve dysfunction. Baffle complications occurred in 6 of the 32 survivors, including superior vena caval stenosis in 4, inferior vena caval stenosis in 1, and pulmonary venous obstruction in 3. Reoperations for baffle obstructions were performed in three patients (8.8%) and balloon angioplasties in two. One patient required permanent pacemaker implantation. Results with the Mustard procedure before 1 month of age show that it can be performed with negligible mortality and a low incidence of late complications at an age comparable to when arterial switching would be performed. Until long-term studies demonstrate superiority of arterial operations, the low operative mortality favors continued evaluation of the neonatal Mustard repair as a valid alternative to the arterial switch. PMID- 1434699 TI - Continuous arteriovenous hemofiltration after cardiac operations in infants and children. AB - Acute renal insufficiency after cardiopulmonary bypass can lead to a significant morbidity from fluid overload and electrolyte disturbance, impede pulmonary gas exchange, and postpone weaning from mechanical ventilation. The limitations placed on free water intake result in severe restriction of nutrition while diuretic therapy causes electrolyte imbalance. Artificial renal support either in the form of peritoneal dialysis or hemodialysis may be complicated by sepsis and hemodynamic instability. We reviewed our experience with the use of continuous arteriovenous hemofiltration, an extracorporeal technique for removal of solutes, toxins, and water in critically ill patients with cardiac failure complicated by acute renal insufficiency and hemodynamic instability after cardiopulmonary bypass. Ten infants and children with renal insufficiency caused by low cardiac output had continuous arteriovenous hemofiltration instituted for indications including sepsis, volume overload, oliguria for more than 24 hours nonresponsive to diuretic therapy, and the need for hyperalimentation. All were supported by mechanical ventilation and receiving high-dose inotropic support. Arterial and venous vascular access was successfully obtained by cannulation of the femoral artery and vein in nine patients. Anticoagulation of the circuit was achieved with heparin infusion (6 to 20 micrograms/kg/hr) and monitored by measurement of activated clotting time. The continuous arteriovenous hemofiltration circuit was replaced if there was clot formation, or at 3 days after placement. Dialysis solution (Dianeal) 1.5% or 0.5% was infused as prefilter dilution. With the use of continuous arteriovenous hemofiltration, 20 to 100 m/hr of ultrafiltrate was removed, which allowed correction of hypervolemia, and caloric intake increased from 13.5 kcal/kg/day to 79.5 kcal/kg/day. Continuous arteriovenous hemofiltration was maintained between 5 hours and 8 days and was well tolerated in all patients. Serum urea and creatinine levels declined during continuous arteriovenous hemofiltration. We conclude that continuous arteriovenous hemofiltration is a safe and effective method for fluid and electrolyte homeostasis and that it thus allows hyperalimentation in infants and children after cardiac operations. PMID- 1434700 TI - Combined mustard and Rastelli operations. An alternative approach for repair of associated anomalies in congenitally corrected transposition in situs inversus [I,D,D]. AB - We report on two patients with congenitally corrected transposition of the great arteries in situs inversus who underwent successful anatomic repair of associated cardiac anomalies--ventricular septal defect and pulmonary outflow tract obstruction. Surgical intervention was influenced by the recently introduced technique of Ilbawi and colleagues in cases of congenitally corrected transposition in situs solitus. Principles of the correction are as follows: (1) patch redirection of venous flows at the atrial level through an incision in the left-sided right atrium; (2) patch closure of the ventricular septal defect through a right ventriculotomy, baffling the left ventricle to the aorta; and (3) valved conduit interposition between the right ventricle and the pulmonary artery. If the ventricular septal defect is restrictive, it can be safely enlarged by extensive resection of the anterosuperior border, because of the posteroinferior location of the bundle of His in this anomaly. With this technique, the left ventricle and the native mitral and aortic valves are recruited for systemic work, with intrinsic long-term advantages. It is, however, a complex procedure involving substantial use of prosthetic material. More experience is necessary to establish whether this approach is superior to currently available physiologic repairs. PMID- 1434701 TI - The Bjork-Shiley valve prosthesis. Analysis of long-term evolution. AB - The long-term follow-up of 831 patients who underwent valve replacement with Bjork-Shiley Delrin and standard Pyrolyte prostheses (341 aortic, 345 mitral, and 145 mitroaortic) between 1971 and 1980 is reviewed. The follow-up concluded in 1985. Cumulative follow-up amounted to 4724 years, with a mean of 5.68 years per patient. Data on survival were obtained in 754 patients (complete follow-up in 90.8% of cases). Perivalvular leak was the most frequent complication in aortic valve replacement, whether isolated or combined, with values significantly higher than those registered in isolated mitral replacement (p < 0.001 in both cases). No correlation was found between this complication and valve calcification, but it was statistically correlated with the size 19 model (p < 0.05). Prosthetic stenosis was more common in mitral than in aortic replacement (p < 0.001), and of the former, size 23 was that most often affected (p < 0.001). The earliest case of mitral pannus was diagnosed 20 months postsurgery, and from 45 months on this pathology was the cause of every case of stenosis. The risk of thromboembolism was similar in aortic, mitral, and double prostheses, while it was the single most frequent complication in isolated mitral replacement. Prosthetic thrombosis was triggered in all cases in which it occurred by discontinuance of anticoagulant therapy. Anticoagulant-induced hemorrhages were more frequent in double replacement than in mitral (p < 0.05) and aortic valve replacement. Endocarditis was the complication that produced the highest mortality rate in all groups; the frequency of this infection was higher among patients with double prostheses when compared with either aortic replacement (p < 0.05) or mitral replacement (p < 0.001). The risk of suffering endocarditis was correlated with the existence of active preoperative infection in patients with mitral prostheses and double prostheses (p < 0.001 in both cases). Overall morbidity was higher in the double replacement group with respect to the mitral group (p < 0.01). The rate of mortality was also higher among the double valve replacement patients when compared with both the aortic (p = 0.0002) and mitral (p = 0.006) groups. PMID- 1434702 TI - Eleven-year follow-up study of aortic or aortic-mitral anulus-enlarging procedure by Manouguian's technique. AB - Although Manouguian's operation is well established, there have been little long term data published on its outcome. From January 1980 to June 1988, 15 patients underwent patch enlargement of the small aortic anulus by Manouguian's approach, either with aortic single valve replacement (7 patients) or with aortic-mitral double valve replacement (8 patients). Follow-up ranged from 3.0 to 11.4 years (mean 8.5) and was completed with a cumulative total of 102 patient-years. One patient died of fulminant hemolysis, probably related to turbulent jet flow and Dacron patch material (operative mortality 6.7%). There were four late deaths, and the actuarial survival, including operative death at 10 years, was 62% +/- 14%. Reoperations were performed seven times in six patients. Most of these complications were not considered to be caused by the anulus-enlarging procedure. Actuarial freedom rate from reoperation at 10 years was 65% +/- 15%. Four patients underwent rereplacement of prostheses for Hancock valve failure during 2.9 to 11.3 years (mean 8.2 years). The anulus enlargement was found to be well healed and presented no problem during reoperation. Surgically induced mitral regurgitation by Manouguian's procedure was observed in two patients. The regurgitation did not progress during follow-up duration of 1.9 to 10.0 years, nor did it cause congestive heart failure. Annular enlargement by Manouguian's procedure with use of mechanical valves is one of the good selections in patients with the narrow aortic valve ring. PMID- 1434703 TI - Comparison of immediate hemodynamic response to closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty in rheumatic mitral stenosis. AB - The hemodynamic response to closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty was compared using 20 patients in each group. All patients had symptomatic rheumatic mitral stenosis with a mitral valve area < 1 cm2, without any left atrial clot, mitral valve calcification, or mitral regurgitation. There was a significant improvement in hemodynamics following intervention in all three groups. The mean pulmonary artery pressure decreased from 49.1 +/- 17.5 to 28.6 +/- 8.3 mm Hg (p < 0.001), 48.8 +/- 12.3 to 34.0 +/- 13.9 mm Hg (p < 0.001), and 46.7 +/- 18.0 to 26.3 +/- 13.7 mm Hg (p < 0.001) in the closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty groups, respectively. The mitral valve area increased from 0.62 +/- 0.27 to 1.5 +/- 0.5 cm2 (p < 0.001), 0.68 +/- 0.24 to 1.5 +/- 0.4 cm2 (p < 0.001), and 0.68 +/- 0.25 to 1.9 +/- 0.8 cm2 (p < 0.001) in the closed mitral commissurotomy, single-balloon, and double-balloon mitral valvuloplasty groups, respectively. The increase in the mitral valve area was maximum in the group with double-balloon mitral valvuloplasty. In the closed mitral commissurotomy group there was a significant rise in left ventricular end-diastolic pressure, from 6.8 +/- 3.9 to 9.3 +/- 3.1 mm Hg (p < 0.001), but this remained unchanged in the single-balloon and double-balloon mitral valvuloplasty groups. Our study shows that single-balloon and double-balloon mitral valvuloplasty are comparable to closed mitral commissurotomy in the immediate hemodynamic response, with a larger valve area in the double-balloon mitral valvuloplasty group. PMID- 1434704 TI - Correction of anterior mitral prolapse. Results of chordal transposition. AB - From 1986 to 1992 102 mitral valve repairs were done for mitral regurgitation due to a degenerative disease. Forty-eight patients had an anterior prolapse or prolapse of both leaflets at initial presentation and underwent chordal transposition from the mural leaflet to the anterior leaflet. The corrective procedure was completed by polytetrafluoroethylene or pericardial posterior annuloplasty. Operative mortality was 2.9%, and follow-up (average 22 months) was 100% complete. There were three postreconstruction valve replacements (one earlier and two later) for a probability of freedom from reoperation of 91.5% +/- 5.2% at 3 years. Freedom from all morbidity was 85.5% +/- 5.5% at 3 years. Postoperative echocardiographic studies demonstrated a good mitral valve function: (1) Eighty-seven percent of patients presented no or mild residual regurgitation; (2) transmitral flow indexes were within the norm; (3) left ventricular outflow tract flow was normal in all patients. This study shows that chordal transposition is a safe and effective technique for prolapse of anterior or both leaflets and improves the chances of repair in patients with mitral degenerative disease. PMID- 1434705 TI - Partial replacement of mitral valve by homograft. An experimental study. AB - Satisfactory long-term clinical results with heart valves have renewed the interest in the use of mitral homografts, despite the technical difficulties with their surgical implantation. This report describes the behavior and viability of the partial mitral homograft in the ortotopic position in a chronic sheep model (n = 25). The 20 surviving animals were studied hemodynamically and were anesthetized and electively put to death 3, 6, 9, and 12 months after the operation. All specimens had a normal mitral valve without signs of infection or thrombosis. Light, scanning, and transmission electron microscopy showed the presence of viable endothelial cells from the recipient covering the graft, signs of reendothelialization, and organized dense collagen tissue. The structural integrity was more evident in the fresh mitral homografts. This method may provide consider improvement in the viability of the mitral homograft, and it could be a valid alternative for repair of mitral valve localized pathology. PMID- 1434706 TI - Tolerance to glyceryl trinitrate in isolated human internal mammary arteries. AB - The purpose of this study was to examine the vascular reactivity of segments of internal mammary artery removed from patients undergoing coronary artery bypass operations. Responses to relaxant and contractile agents were compared in arteries removed from patients who had or had not been treated with glyceryl trinitrate after admission to the hospital until operation. Segments of mammary artery were removed from 13 patients who underwent coronary artery bypass grafting. Endothelium-containing rings of artery, 3 to 5 mm long, were suspended in physiologic saline solution in 20 ml organ baths. Responses to the endothelium dependent relaxant acetylcholine and the endothelium-independent relaxants glyceryl trinitrate and sodium nitroprusside were compared. In addition, contractile responses to phenylephrine and 9,11-dideoxy-9 alpha,11 alpha methanoepoxy prostaglandin F2 alpha (U46619) were examined. Glyceryl trinitrate induced relaxation was significantly impaired in mammary artery segments from patients treated with that nitrate before operation; the responses to acetylcholine and sodium nitroprusside were not affected. Previous treatment with glyceryl trinitrate also reduced the contractile responses to both phenylephrine and U46619. These studies indicate that treatment of patients with glyceryl trinitrate before operation induces significant tolerance to this agent in the mammary artery; however, there was no evidence of cross tolerance to sodium nitroprusside or the endothelium-dependent vasodilator acetylcholine. Glyceryl trinitrate may therefore not always be effective in dilating mammary artery grafts and sodium nitroprusside may be a more effective dilator of the internal mammary artery in patients who have been treated with glyceryl trinitrate before operation. PMID- 1434707 TI - Antimineralization treatments for bioprosthetic heart valves. Assessment of efficacy and safety. AB - Since calcification limits the durability of contemporary bioprosthetic heart valves, antimineralization treatments are being widely investigated. Potential antimineralization treatments must have sustained prevention of mineralization without adverse effects. The preclinical investigation of efficacy and safety of antimineralization treatments comprises four essential steps: (1) subcutaneous implantation in small animals, (2) in vitro biomechanical studies of hemodynamics and durability, (3) morphology of unimplanted valves, and (4) circulatory implants in large animals. PMID- 1434708 TI - The effect of ambient temperature on papaverine-induced relaxations in canine saphenous veins. AB - This study was designed to measure the effect of ambient temperature (25 degrees C) on papaverine-induced relaxations in canine saphenous veins. Segments of vein were suspended in water-jacketed tissue baths at 37 degrees C, and isometric tension was recorded. After equilibration, veins were preconstricted by a median effective dose of norepinephrine 2 x 10(-6) mol/L at either 25 degrees C or 37 degrees C. Consequent dose-dependent relaxations showed that papaverine (10(-7) to 10(-3) mol/L was three times more potent as a dilator at 37 degrees C than at 25 degrees C, with half-maximal relaxations occurring at 2.2 x 10(-5) mol/L and 6.4 x 10(-5) mol/L, respectively. A 10(-4) mol/L dose of papaverine completely relaxed veins at 37 degrees C, whereas veins at 25 degrees C never fully relaxed even at ten times the standard concentration. In addition, the time for half maximal relaxation with a 10(-4) mol/L dose of papaverine averaged 40 minutes at 25 degrees C compared with 22 minutes at 37 degrees C; this is indicative of a reduced relaxation rate at the lower temperature. These data show that papaverine is a slower and less potent dilator of canine saphenous veins at 25 degrees C than at 37 degrees C. This may have implications for the use of papaverine in the operating room, where it is usually applied at ambient temperature to reduce vasospasm of the saphenous vein during coronary artery bypass procedures. PMID- 1434709 TI - Different effects of activated platelets in the right gastroepiploic and internal mammary arteries. Implications for coronary artery grafting. AB - The right gastroepiploic artery is increasingly utilized as an alternative coronary bypass conduit, although postoperative spasm can represent a problem. Platelet-vessel wall interactions are important determinants of graft function and patency. We studied the effects of activated platelets in porcine and human gastroepiploic and mammary arteries. Arterial rings were suspended in organ chambers for isometric tension recording. In the porcine and human gastroepiploic arteries with or without endothelium contracted with norepinephrine, activated platelets evoked only further and strong contraction. In contrast, in the porcine and human mammary arteries, endothelium-dependent relaxations to platelets mediated by nitric oxide were noted, particularly in rings preincubated with the thromboxane A2 receptor antagonist SQ-30741 and the 5-hydroxytryptamine (5HT2) serotonergic receptor antagonist ketanserin. Although endothelium-dependent and endothelium-independent relaxation to bradykinin and the nitrovasodilator 3 morpholino sydnonimine were more pronounced in the gastroepiploic than in the mammary artery, norepinephrine, serotonin, and potassium chloride evoked much stronger contractions in the former than in the latter. Thus activated platelets induce pronounced contraction of the gastroepiploic artery that may contribute to postoperative spasm. The administration of antiplatelet drugs and vasodilators that prevent the effects of thromboxane A2 and serotonin may be beneficial for gastroepiploic graft function. PMID- 1434710 TI - The effects of different techniques of internal mammary artery harvesting on sternal blood flow. AB - We investigated chest wall blood flow in a canine model to determine if the technique used to harvest the mammary artery has a differential effect on residual chest wall blood flow. Eight dogs underwent bilateral internal mammary artery mobilization; one artery was harvested as a pedicle and the other was harvested as a skeletonized vessel. Residual blood flow to the chest wall distribution of each artery was measured with radioactive microspheres. Chest wall blood flow was significantly decreased from preharvest levels after internal mammary artery mobilization regardless of the technique used. Tissue blood flows decreased to 46.9%, 22.1%, and 41.2% of baseline values for the manubrium (p < 0.01), sternum (p < 0.001), and ribs (p < 0.05), respectively. Residual sternal blood flow on the side of the skeletonized vessel was significantly greater than on the side of the pedicle graft (2.60 +/- 0.68 versus 1.27 +/- 0.27 cm3/min/100 gm, p < 0.001). We conclude that minimization of tissue mobilization during internal mammary artery harvesting may reduce sternal devascularization. This finding may have clinical significance with respect to lowering the incidence of sternal wound complications in coronary bypass surgery using the internal mammary artery as a bypass conduit. PMID- 1434711 TI - Evaluation of surgical procedures. Changing patterns of patient selection and costs in heart transplantation. AB - During the past 4 years we have observed a marked increase in costs of heart transplantation in our center. This trend coincides with a shift in our recipient population toward the more severely ill patients. The percentage of patients bound for the intensive care unit has doubled. In analyzing the components of cost, we find that the length of stay, both in special care and regular nursing units, accounts for most of the cost increase. In our study of outcomes we find no significant difference in survival, at 1 month and 1 year, between recipients operated on from the intensive care unit and those not in intensive care. We find that at 1 year after transplantation, approximately 80% of patients are rehabilitated, which we define as the ability to work or to go to school. Only 20% of patients are off disability rolls, however, primarily because of problems related to insurance and the cost of continuing care, including drugs. We conclude that the comprehensive evaluation of surgical procedures requires an approach that balances costs with results on a continuing and long-term basis. PMID- 1434712 TI - The effects of donor-recipient size disparity in infant and pediatric heart transplantation. AB - To determine the effect of heart donor and recipient size mismatches in infant and pediatric heart transplantation, we studied all 69 patients (age 1 day to 11 years) having 71 orthotopic heart transplants from 1985 to 1989. Patients were divided into three groups based on donor to recipient weight ratios. Group I comprised 13 heart transplants with a donor to recipient weight ratio less than 0.95 (mean 0.81, range 0.48 to 0.94); group II comprised 29 heart transplants with a weight ratio between 0.95 and 1.60 (mean 1.28); and group III had 27 heart transplants with weight ratios greater than 1.60 (mean 2.2, range 1.61 to 3.09). All chests were closed primarily. The cardiothoracic ratio by chest radiography was significantly larger in group III (p = 0.0002); 75% of group III patients had periods of lobar or complete lung collapse by chest radiography compared with 28% of group II and 19% of group I patients (p < 0.05). Despite this, there was no difference in the number of days of ventilator support for any group (p = 0.92). There was no difference in graft ischemic time or inotropic drug use among groups, nor were differences found in the cardiac systolic function parameters of left ventricular preejection time (p = 0.975), left ventricular ejection time (p = 0.975), left ventricular fiber shortening (p = 0.97), and left ventricular fractional shortening (p = 0.596). Thus despite a high incidence of transient lobar or complete lung collapse in high donor to recipient weight ratio transplants, large donor heart size produces very little clinical impairment in recipient lung function. Size mismatches do not influence cardiac systolic function. Overall, large size mismatches appear to be very well tolerated in infant and pediatric heart transplantation. PMID- 1434713 TI - The myocardial recovery mode after cold storage for transplantation with Collins' solution and cardioplegic solution. A functional and metabolic study in the rat heart. AB - Mechanisms and kinetics of the effects of the ionic composition of two different storage solutions, an intracellular type and an extracellular type, were analyzed by examining the myocardial functional and metabolic recovery processes during the early reperfusion periods after 3 hours of cold storage using an isolated perfused working rat heart model. The hearts were stored either in our own cardioplegic solution (group 1) or in Collins' solution (group 2) for 3 hours at 4 degrees C and were then reperfused. The electromechanical activity in group 1 was elevated, as indicated by a higher incidence of ventricular fibrillation at 5 minutes of reperfusion (group 1: 5/6; group 2: 0/5; p < 0.05). The coronary flow rate in group 2 was significantly lower, at least for the first 15 minutes after reperfusion, than that of group 1, suggesting the possible existence of vasoconstriction in group 2. Although myocardial oxygen uptake during this period was smaller in group 2, the recovery of myocardial high-energy phosphate levels was better and creatine kinase leakage was less in group 2. The recovery of aortic flow after 30 minutes of reperfusion was significantly better in group 2 (group 1, 59.1 +/- 5.8%; group 2, 71.7 +/- 6.0%; p < 0.01), although the early recovery was somewhat worse in group 2. These data suggest that the heart stored in an intracellular-type solution, compared with one stored in an extracellular type solution, recovers in an electromechanically suppressed fashion during the early reperfusion phase, associated with a better metabolic recovery and a slower but larger functional recovery. The disadvantage of the intracellular-type solution, however, may be its effect on the increase of coronary vascular resistance during the early reperfusion period. PMID- 1434714 TI - Growth potential of porcine reduced-size mature pulmonary lobar transplants. AB - The use of mature pulmonary lobes for pediatric lung transplantation has recently been described. Successful application of this technique could help alleviate the pediatric donor lung shortage. Whether an already mature lobe can grow by forming new alveolar units after transplantation into a developing recipient is not known. We therefore measured functional residual capacity, fixed lung volume and weight, alveolar size and air space volume percent, and total number of alveoli in mature left lower lobe porcine lung transplants 12 weeks after transplantation into growing piglets. Comparisons were made with nontransplanted mature left lower lobes to determine if functional or morphologic growth had occurred after transplantation. The transplanted and control lobes were all taken from 6-month old animals (mean body weight 105 +/- 4 kg). Recipients of the transplanted lobes were 9 weeks old and weighed 22 +/- 2 kg. By the end of the 12-week holding period, the recipient animals increased their body weight approximately fourfold (85 +/- 4 kg). No significant differences were seen in functional residual capacity or morphologic analysis of total alveolar number and alveolar size between the transplanted and nontransplanted lobes (p = not significant). Although the reduced-size mature porcine lobar transplants did not display a significant increase in either functional residual capacity or total alveolar number, there was significant growth of the transplanted mature lobes as determined by fixed volume and total lobar weight (p < or = 0.05 versus control animals). PMID- 1434716 TI - The use of combined antegrade-retrograde infusion of blood cardioplegic solution in pediatric patients undergoing heart operations. AB - The benefits of combined antegrade-retrograde infusion of blood cardioplegic solution are becoming well known in adult coronary and valvular heart operations. Many of these advantages relate directly to the pediatric patient. They include prompt arrest and even distribution, particularly with aortic insufficiency or open aortic root, avoiding or limiting ostial cannulation, allowing uninterrupted surgical procedures, and flushing air/debris from the coronary arteries. We therefore report on the first 123 pediatric patients at the University of California, Los Angeles, to receive myocardial protection with antegrade (aortic) infusion in conjunction with retrograde (coronary sinus) infusion of blood cardioplegic solution. We employed a retroplegia catheter with a self-inflating and deflating occlusion balloon on the tip of a pressure-monitored infusion cannula that remains in the coronary sinus during the operation. Induction blood cardioplegic solution, 30 ml/kg in equally divided doses, is administered in the coronary sinus first antegrade at an aortic pressure less than 80 mm Hg, followed by retrograde infusion at less than 40 mm Hg. Maintenance cardioplegic solution (15 ml/kg) is administered every 20 minutes through one or both of the infusion cannulas, depending on the surgical procedure. Patients' ages ranged from 1 week to 16 years with a mean of 4.6 years. The following procedures were included in descending order: Fontan 20, atrioventricular valve repair/replacement (and complete atrioventricular canal) 16, aortic root/Konno/Ross 16, Rastelli 13, aortic valve repair/replacement 13, ventricular septal defect (and double-outlet right ventricle) 13, tetralogy of Fallot 10, coronary artery reimplantation/fistula repair 6, truncus arteriosus 4, arterial switch 3, bidirectional Glenn 2, sinus venosus 2, and aortopulmonary window, Senning, Stansel, interrupted aortic arch, and Ebstein's, 1 each. Aortic crossclamp times ranged from 6 to 219 minutes with a mean of 87 minutes. Myocardial oxygen consumption data for a series of six patients indicated the supplemental benefit for retrograde infusion of cardioplegic solution along with antegrade infusion, particularly in hypertrophied myocardium. Three deaths occurred (2.4% 30-day mortality), in the following patients: the first with truncus arteriosus and interrupted aortic arch, the second with complete atrioventricular canal and pulmonary hypertension, and the third with truncal valve regurgitation and replacement. There were no complications related to the retroplegia catheter. From this initial positive experience, we conclude that (1) combined antegrade retrograde infusion of blood cardioplegic solution can be safely used in an expanding number of pediatric heart operations in all age groups, and (2) combined antegrade-retrograde infusion of blood cardioplegic solution may provide additional myocardial protection, with excellent surgical outcome, in complex congenital heart repairs. PMID- 1434715 TI - Lazaroid U74500A as an additive to University of Wisconsin solution for pulmonary grafts in the rat transplant model. AB - Lazaroids are a class of novel 21 aminosteroids. They have been reported to be potent inhibitors of lipid peroxidation, which is a major contributing factor to ischemia-reperfusion injury in the lung. A Lewis rat orthotopic left lung isotransplant model was used to investigate the effects of the lazaroid U74500A on pulmonary preservation. The heart-lung blocks of donor rats were flushed with and then stored in either standard University of Wisconsin solution or University of Wisconsin solution with 30 mumol/L of U74500A substituted for the dexamethasone. After 6 or 12 hours of cold storage at 0 degrees C, the left lungs were transplanted into recipient rats and reperfused for 1 hour. Pulmonary function was assessed by measuring oxygen and carbon dioxide tensions in arterial blood after removal of the right lung. Lipid peroxide concentrations were measured as a thiobarbituric acid-reactive substance. Although arterial oxygen and carbon dioxide pressures and water content after 6 hours of preservation followed by reperfusion were similar in both the lazaroid and dexamethasone groups, lipid peroxide concentration was significantly higher in the dexamethasone group (0.88 +/- 0.07 mumol/gm) than in the lazaroid group (0.54 +/- 0.07 mumol/gm) (p < 0.01). After 12 hours of preservation, there were significant differences between the lazaroid and dexamethasone groups in arterial oxygen pressure (339 +/- 70 vs 27 +/- 3 mm Hg, p < 0.01), arterial carbon dioxide pressure (24.3 +/- 2.7 vs 47.7 +/- 7.0 mm Hg, p < 0.001), and lipid peroxide concentrations (0.69 +/- 0.07 vs 1.30 +/- 0.09 mumol/gm, p < 0.001). We conclude that addition of U74500A to the flush and storage solution enhances the preservation of the pulmonary graft in this transplant model. PMID- 1434717 TI - The effectiveness of University of Wisconsin solution on prolonged myocardial protection as assessed by phosphorus 31-nuclear magnetic resonance spectroscopy and functional recovery. AB - The effectiveness of the University of Wisconsin solution on extended myocardial preservation was examined in this study using phosphorus 31-nuclear magnetic resonance spectroscopy. Isolated perfused rat hearts were arrested and stored in four preservation solutions: group 1, modified Krebs-Henseleit solution; group 2, modified St. Thomas' Hospital solution; group 3, oxygenated modified St. Thomas' Hospital solution containing 11 mmol/L glucose; and group 4, University of Wisconsin solution. The changes in myocardial high energy phosphate profiles and the intracellular pH values were measured during 12 hours of cold (4 degrees C) global ischemia and 90 minutes of normothermic reperfusion. Following ischemia, the hearts were assessed for hemodynamic recovery and myocardial water content. During ischemia, adenosine triphosphate depletion was observed in all groups; however, after 5 hours of ischemia, the adenosine triphosphate levels were significantly higher in group 3 compared with the other groups (adenosine triphosphate levels at 6 hours in mumol/gm dry weight: group 3, 7.6; group 4, 3.2; group 2, < 1; p < 0.025). The tissue water content at the end of ischemia was lower with the University of Wisconsin solution compared with the modified St. Thomas' Hospital solution or the oxygenated modified St. Thomas' Hospital solution (in ml/gm dry weight: group 4, 3.0; group 2, 4.4; group 3, 3.9; p < 0.05). The adenosine triphosphate repletion during reperfusion was greater with the University of Wisconsin solution compared with the modified St. Thomas' Hospital solution or the oxygenated modified St. Thomas' Hospital solution (12 mumol/gm dry weight in group 4; 8.1 in group 2; 9.0 in group 3; p < 0.05). Similar findings were obtained for the recovery of left ventricular pressure (in percent of preischemic control: group 4, 70%; group 2, 42%; group 3, 52%; p < 0.01) and coronary flow (group 4, 61%; group 2, 49%; group 3, 49%; p < 0.05). These data suggest that preservation with the University of Wisconsin solution affords improved hemodynamic recovery, enhanced adenosine triphosphate repletion, and reduced tissue edema upon reperfusion; however, oxygenated St. Thomas' Hospital solution with glucose is associated with the preservation of higher myocardial adenosine triphosphate levels during prolonged cold global ischemia. In conclusion, these data indicate that the University of Wisconsin solution might improve graft tolerance of ischemia in clinical heart transplantation. PMID- 1434718 TI - Crystalloid cardioplegia and hypothermia do not impair endothelium-dependent relaxation or damage vascular smooth muscle of epicardial coronary arteries. AB - Canine hearts were arrested with crystalloid cardioplegic solution (45 minutes at 7 degrees C) to determine whether either cardioplegia or hypothermia impairs the production of endothelium-derived relaxing factor or damages the vascular smooth muscle of epicardial coronary arteries. In addition, isolated coronary artery segments were exposed to either cold (7 degrees C) or warm (37 degrees C) crystalloid cardioplegic solution and physiologic salt solution in vitro for 45 minutes. After cardiac arrest or incubation with the solutions, segments of epicardial coronary artery were prepared and studied in organ chambers. Cardioplegic arrest of the heart or exposure to cardioplegic solution in vitro (7 degrees or 37 degrees C) did not alter endothelium-dependent relaxation of epicardial coronary artery segments in response to adenosine diphosphate or acetylcholine (10(-9) to 10(-4) mol/L). Cardioplegic arrest did not alter G protein-mediated, endothelium-dependent relaxation in response to sodium fluoride. In addition, smooth muscle contraction in response to potassium ions (voltage-dependent) or prostaglandin F2 alpha (receptor-dependent) and relaxation in response to isoproterenol (cyclic adenosine monophosphate-mediated) or sodium nitroprusside (cyclic guanosine monophosphate-mediated) was unaltered after exposure to cardioplegic solution or hypothermia. These experiments demonstrate that hyperkalemic crystalloid cardioplegia does not irreversibly alter function of epicardial coronary arteries. We hypothesize that coronary artery endothelial cell dysfunction identified in previous studies of cardioplegia may have been due to the effects of barotrauma or shear stress on the vasculature and not the effect of cardioplegia per se. PMID- 1434719 TI - Enhancement of low coronary reflow improves postischemic myocardial function. AB - The effect of reperfusion coronary vasodilatation on postischemic myocardial mechanical function has been investigated in the isolated working rat heart. After a working period to assess control function, all the hearts were subjected to a single infusion (10 ml) of St. Thomas' Hospital cardioplegic solution No. 1 at 4 degrees C and were kept immersed in the same solution for 4 hours at 4 degrees C. Then hearts (six in each group) were initially reperfused at 37 degrees C for 10 minutes, either with ordinary reperfusate (Krebs-Henseleit bicarbonate buffer) or with reperfusate containing additional coronary dilator. After this period, all hearts were subjected to a further 5 minutes of ordinary reperfusate before being put back into the working mode to assess functional recovery. Mean reperfusion coronary flows and the steady coronary flow measured after 10 minutes of reperfusion in ml/min +/- SEM were--Krebs (control): 17.4 +/- 0.39 and 13.4 +/- 0.40; adenosine (3.75 mumol/L): 19.9 +/- 0.6 and 16.7 +/- 0.8; papaverine (0.05 mmol/L): 21.8 +/- 2.3 and 17.3 +/- 1.8; dipyridamole (2 mmol/L): 20.7 +/- 1.7 and 17.9 +/- 1.0; nitroglycerin (15 mg/L): 20.5 +/- 0.45 and 19.9 +/ 1.4; diltiazem (0.05 mmol/L): 19.6 +/- 2.98 and 17.7 +/- 1.8; calcitonin gene related peptide (0.03 mmol/L): 20.8 +/- 0.69 and 18.0 +/- 1.3; 5 hydroxytryptamine (0.01 mmol/L): 19.2 +/- 0.53 and 16.9 +/- 0.80. Mean postischemic recovery of cardiac output, peak aortic pressure, and differentiation of pressure were expressed as percent of preischemic control +/- SEM were--Krebs: 54.1 +/- 2.8, 69.1 +/- 2.8, and 53.9 +/- 3.0; adenosine: 78.0 +/ 5.6, 89.5 +/- 2.9, and 69.1 +/- 1.9; papaverine: 81.8 +/- 3.9, 91.8 +/- 3.1, and 71.0 +/- 4.1; dipyrdamole: 67.3 +/- 3.3, 84.3 +/- 2.3, and 75.0 +/- 2.7; nitroglycerin: 83.1 +/- 4.8, 79.7 +/- 2.7, and 69.0 +/- 0.5; diltiazem: 76.5 +/- 3.7, 85.9 +/- 2.9, and 73.3 +/- 1.7; calcitonin gene-related peptide: 79.5 +/- 3.6, 90.0 +/- 4.9, and 75.4 +/- 3.9; 5-hydroxytryptamine: 71.6 +/- 3.2, 85.5 +/- 3.5, and 67.9 +/- 4.8. There was a positive correlation between mean reperfusion coronary flow, steady coronary flow, and postischemic recovery of cardiac output, peak aortic pressure, and differentiation of pressure. Mean reperfusion coronary flow, steady coronary flow, and postischemic recovery of cardiac output, peak aortic pressure, and differentiation of pressure were significantly greater in groups reperfused with vasodilators (p < 0.05) compared with control values.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1434720 TI - Continuous warm blood cardioplegia preserves cardiac autonomic function. AB - We studied in anesthetized dogs, the effects of cardiopulmonary bypass with normothermic whole blood, crossclamping of the aortic root, and continuous warm blood cardioplegia on the ability of the efferent sympathetic nervous system to augment the heart and that of the efferent parasympathetic nervous system to depress the heart. In control states, heart rate, atrial force of contraction, and right and left ventricular wall systolic pressures were augmented by stimulation of the intrathoracic efferent sympathetic nervous system and by administration of isoproterenol into the systemic circulation. After 1 hour of normothermic cardiopulmonary bypass that utilized aortic crossclamping and continuous perfusion of the coronary arteries with normothermic blood (20 mEq/L potassium), cardiac-augmenting effects induced by the efferent sympathetic nervous system and by isoproterenol were similar. Depressive responses elicited by the efferent parasympathetic nervous system were also unaffected by these procedures. Continuous warm blood cardioplegia does not result in impairment of the efferent sympathetic nervous system regulating the heart. PMID- 1434721 TI - Influence of pH management on hemodynamics and metabolism in moderate hypothermia. AB - In moderate hypothermia, three different concepts of pH management have been described to date: pH-stat, alpha-stat, and alkalinity. In our study these pH strategies were compared in adult sheep, with animals serving as their own controls for direct comparability. Hemodynamic parameters, such as mean aortic pressure (from 109 +/- 12 to 72 +/- 23 mm Hg), cardiac output (from 5.55 +/- 1.25 to 4.5 +/- 0.82 L/min), and systemic oxygen consumption (from 3.73 +/- 0.8 to 1.81 +/- 0.4 ml/kg/min), decreased significantly with alpha-stat at 28 degrees C from values for normothermia. No marked or even significant differences were found among the three pH strategies in any value, with the exception of body oxygen consumption. The difference of 2% between pH-stat and alpha-stat, at 0.06 ml oxygen/kg/min, was significant (p < or = 0.05), however of no practical relevance because hypothermia itself caused a decrease of nearly 52%. With regard to myocardial parameters, pH-stat impaired myocardial function compared with both alpha-stat and alkalinity. At nearly identical mean aortic pressures and cardiac outputs, myocardial oxygen consumption reached the highest level in pH-stat (7.65 ml oxygen/100 gm/min; alpha-stat, 6.76 ml oxygen/100 gm/min; p < or = 0.05). Myocardial efficiency thus decreased from 21% (alpha-stat) to 17% (pH-stat). No evident changes in hemodynamic and metabolic values were found for alkalinity vs alpha-stat. The best response to continuously infused epinephrine, however, was found with alkalinity. According to our data there was an impairment of myocardial function without any evident further reduction in body metabolism with pH-stat vs alpha-stat. There were, however, no marked metabolic or hemodynamic differences between alkalinity and alpha-stat, with the exception of a better preservation of sensitivity to adrenergic stimuli with alkalinity. PMID- 1434722 TI - A comparison of the effects on neuronal Golgi morphology, assessed with electron microscopy, of cardiopulmonary bypass, low-flow bypass, and circulatory arrest during profound hypothermia. AB - Adult swine (n = 18) were studied to compare the effects on neuronal morphology of hypothermic circulatory arrest with hypothermic very-low-flow cardiopulmonary bypass. Animals were anesthetized with halothane and prepared in a standard manner for nonpulsatile cardiopulmonary bypass. Monitored variables included mean arterial pressure, arterial blood gases, the processed electroencephalogram, and subdural brain temperature. Bypass was initiated with pump flows of 100 ml.kg 1.min-1, and mean arterial pressure was kept above 50 mm Hg at all times. Animals were cooled to 18 degrees C, using a heat exchanger, and were randomly assigned to one of three groups. Group 1 animals were control animals who underwent 1 hour of hypothermic cardiopulmonary bypass. Group 2 animals underwent 1 hour of circulatory arrest. Group 3 animals underwent 1 hour of very-low-flow cardiopulmonary bypass (10% of normal). At the end of the 1 hour of hypothermic bypass, very-low-flow bypass, or arrest period, animals were rewarmed to 37 degrees C with normal bypass flows, and normothermic perfusion continued for 1 additional hour. Animals were then perfusion fixed with formalin and the brains were removed for electron microscopic analysis. Electron microscopic analysis was used to determine the effects of treatment and was limited to 20 neurons of the CA1 sector of the hippocampus in each animal. Golgi bodies were identified and classified as normal, mildly affected, or severely affected. Animals subjected to either very-low-flow bypass or circulatory arrest had significantly more severely affected and significantly fewer normal Golgi bodies than control animals (p < 0.001). Animals maintained with very-low-flow bypass, however, had significantly more severely affected and fewer normal Golgi bodies than animals subjected to circulatory arrest (p < 0.001). We conclude that under the conditions of this experiment very-low-flow hypothermic cardiopulmonary bypass is associated with significantly greater neuronal Golgi abnormalities than total circulatory arrest. PMID- 1434723 TI - Cognitive outcome after cardiac operations. Relationship to intraoperative computerized electroencephalographic data. AB - Cardiopulmonary bypass frequently causes new postoperative neuropsychologic deficits. To assess whether these deficits could be predicted or limited, we monitored 29 patients receiving bypass intraoperatively with an on-line computerized electroencephalograph. We hypothesized that the 15 patients whose cerebral perfusion pressure was adjusted on the basis of this electroencephalographic data would have fewer postoperative deficits than the 14 patients whose pressure was monitored on the basis of systemic pressure. The results showed that new postoperative cognitive deficits in both groups were less prevalent than in previous studies, but there was not a significant difference in outcomes between the two groups. The intraoperative electroencephalographic records correlated with surgical, but not neuropsychologic, outcome. It is concluded that careful attention to intraoperative cerebral perfusion pressure may decrease the prevalence of postoperative neuropsychologic complications, but that the use of a computerized electroencephalograph does not necessarily contribute to an improved outcome. PMID- 1434724 TI - Transesophageal echocardiography predicts successful withdrawal of ventricular assist devices. AB - Transesophageal echocardiography has been found to be an effective technique for the real-time assessment of myocardial and valvular function in postoperative patients. To determine the value of transesophageal echocardiography in patients with mechanical assist devices, we performed daily, bedside transesophageal echocardiography on 16 patients with right (n = 3), left (n = 1), or biventricular assist devices (n = 12). We obtained four-chamber and short-axis views in all patients. Valvular function and the presence of left-to-right shunts were evaluated by means of color flow Doppler imaging. During the echocardiographic study ventricular assist device flow was diminished to less than 1.5 L/min, and inotropic agents (dobutamine or epinephrine) were given to assess ventricular reserve. Changes in day-to-day ventricular function were assessed in comparisons made by two observers (one unaware of the study sequence) using a semiquantitative method for wall motion analysis. The left ventricular wall motion scores in the patients successfully weaned from left or biventricular assist devices (n = 5) improved (14.2 +/- 1.6 versus 8.2 +/- 1.5, p < 0.0001). The scores did not improve in patients who remained dependent on the devices (n = 8). Two patients with only right ventricular assist devices were successfully weaned after documentation of improvement of right ventricular function by transesophageal echocardiography. Transesophageal echocardiography documented a clot compressing the heart in three patients; intracavitary thrombi were seen in two other patients. Marked hemodynamic improvement occurred after surgical decompression. In conclusion, transesophageal echocardiography is a safe, effective method for the assessment of ventricular function of patients on ventricular assist device support. In addition, it allows one to assess valvular function and the presence or absence of impaired ventricular filling. PMID- 1434725 TI - The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations. AB - It has been suggested that desmopressin acetate has been effective in reducing hemorrhage after coronary artery bypass grafting in patients receiving aspirin before operation. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine the effectiveness and safety of desmopressin in these patients. Sixty-five patients pretreated with aspirin within 7 days before their scheduled elective coronary artery bypass grafting were randomized to receive desmopressin (0.3 micrograms/kg) or placebo after cessation of bypass and reversal of heparin with protamine. The demographic characteristics and last dose of aspirin were similar in both groups. There was a significant reduction in postoperative blood loss noted between groups for both chest tube blood loss (833 +/- 311 ml for the 1-desamino-8-D-arginine vasopressin [desmopressin] group versus 1176 +/- 674 ml for the placebo group; p = 0.016) and total blood loss (1215 +/- 381 ml for the desmopressin group versus 1637 +/- 761 ml for the placebo group; p = 0.0097). Despite the differences in blood loss between the two groups, the red cell transfusions were not significantly different, but the use of platelets was less in the desmopressin group and almost achieved statistical significance (p = 0.053). Neither was there a difference in the occurrence of thrombotic complications between groups. It appears that desmopressin in this specific subgroup of patients receiving preoperative aspirin is effective as a prophylactic agent for reduction of postsurgical hemorrhage. PMID- 1434726 TI - Comparative study of cefazolin, cefamandole, and vancomycin for surgical prophylaxis in cardiac and vascular operations. A double-blind randomized trial. AB - Three-hundred twenty-one adults undergoing cardiac or major vascular operations were randomized to receive intravenous cefazolin, cefamandole, or vancomycin for prophylaxis against surgical infection in a double-blind trial. All three regimens provided therapeutic blood levels throughout operation in patients studied undergoing cardiopulmonary bypass. The prevalence of surgical wound infection was lowest with vancomycin (4 infections [3.7%] versus 14 [12.3%] and 13 [11.5%] in the cefazolin and cefamandole groups, respectively; p = 0.05); there were no thoracic wound infections in cardiac operations in the vancomycin group (p = 0.04). The mean duration of postoperative hospitalization was lowest in the vancomycin group (10.1 days; p < 0.01) and highest in the cefazolin group (12.9 days). Prophylaxis with vancomycin or cefamandole, compared with cefazolin, did not prevent nosocomial cutaneous colonization by methicillin-resistant coagulase-negative staphylococci; colonization or infection with vancomycin resistant staphylococci or enterococci was not detected. Adverse effects attributable to the prophylactic regimen were infrequent in all three groups. Eight patients given vancomycin became hypotensive during administration of a dose, despite infusion during a 1-hour period; however, slowing the rate of administration and pretreating with diphenhydramine allowed vancomycin to be resumed and prophylaxis completed uneventfully in five of the patients. We conclude that administration of vancomycin (approximately 15 mg/kg), immediately preoperatively, provides therapeutic blood levels for surgical prophylaxis throughout most cardiac and vascular operations, resulting in protection against postoperative infection superior to that obtained with cefazolin or cefamandole. Vancomycin deserves consideration for inclusion in the prophylactic regimen (1) for prosthetic valve replacement and prosthetic vascular graft implantation, to reduce the risk of implant infection by methicillin-resistant coagulase-negative staphylococci and enterococci; (2) for any cardiovascular operation if the patient has recently received broad-spectrum antimicrobial therapy; and (3) for all cardiovascular operations in centers with a high prevalence of surgical infection with methicillin-resistant staphylococci or enterococci. Guidelines for dosing and administration of vancomycin for cardiovascular surgical prophylaxis are provided. PMID- 1434727 TI - Output power and metabolic input power of skeletal muscle contracting linearly to compress a pouch in a mock circulatory system. AB - Output power and metabolic input power values were determined for unconditioned canine latissimus dorsi (two), gastrocnemius (seven), and triceps (three) muscles contracting linearly to cause compression of a doubly valved pouch in a hydraulic model of the circulation. The motor nerves to the muscles were stimulated tetanically with 450 msec trains of 0.1 msec pulses having a frequency of 50/sec. The muscles were contracted 10, 20, 30, and 40 times per minute and pouch output in milliliters per minute was measured directly for each muscle at each contraction (train) rate. The output power in milliwatts was determined by two methods: (1) by using the pouch output and the pressure rise imparted to the stroke volume (average power) and (2) by using the pressure-volume loop. Metabolic input power in milliwatts was determined from the oxygen consumption in milliliters per minute of the working muscle. It was found that as the pouch output was increased, the pouch output power and the metabolic input power both increased. The average power output was slightly less than that computed from the pressure-volume loop. The mean output power values, when pumping at L liters per minute, were 0.62 L (average) and 0.75 L mW/gm (pressure-volume loop) for the latissimus dorsi muscles; 0.83 L (average) and 1.16 L mW/gm (pressure-volume loop) for the gastrocnemius muscles; and 0.55 L (average) and 0.66 L mW/gm (pressure-volume loop) for the triceps muscles. The percent efficiency of energy conversion ranged from 9.2% to 17.8% for the latissimus dorsi muscles, from 5.1% to 19.5% for the gastrocnemius muscles, and from 10.5% to 27.3% for the triceps muscles. However, it should not be concluded that one muscle type is better than another on the basis of percent efficiency because efficiency does not take endurance into account. An important observation in this study relates to the large output obtained with the three linearly contracting muscle types. All were capable of pumping in excess of 1.5 L/min. A second observation relates to the absence of fatigue, although determination of endurance was not an objective in these studies. PMID- 1434728 TI - Subglottic tracheal resection and synchronous laryngeal reconstruction. AB - Postintubation injury of the upper airway commonly results in stenotic lesions of the larynx, subglottis, and adjacent trachea. The traditional approach to surgical correction is laryngofissure for the laryngeal component and staged plastic reconstruction of the subglottic stenosis. Reported results are variable and unpredictable, and permanent extubation is impossible in a significant number of patients. We report experience with 15 patients with combined laryngeal, subglottic, and tracheal stenosis who were managed by a one-stage operation: circumferential resection of the subglottis and trachea with primary thyrotracheal anastomosis, combined with laryngofissure and laryngeal reconstruction. These procedures required the collaboration of the Departments of Otolaryngology and Thoracic Surgery of the Toronto General Hospital. Between 1972 and 1991, our thoracic surgical division did 53 circumferential subglottic tracheal resections with primary thyrotracheal anastomosis for benign disease. There were no operative deaths and 51 of 53 patients were successfully extubated. In 15 of these patients, a concomitant laryngofissure for laryngeal reconstruction was required. Laryngeal repair included excision or incision of interarytenoid scar (n = 13), interarytenoid mucosal graft (n = 6), or mobilization of cricoarytenoid joint (n = 3). A temporary laryngotracheal stent (usually a Montgomery T tube) was maintained after the operation in all cases (duration 3 to 42 months). Thirteen of these 15 patients are now permanently extubated and none has functionally significant restenosis. Vocal function is satisfactory to good in these patients. The approach described for these combined laryngotracheal lesions provides better results than those reported with traditional staged and plastic techniques of reconstruction. The collaboration of the departments of otolaryngology and thoracic surgery was essential to achieve these results. PMID- 1434729 TI - Second primary lung cancer after bronchial sleeve resection. Treatment and results in eleven patients. AB - During the years 1960 to 1989, 145 patients underwent sleeve lobectomy or sleeve resection of a main bronchus. Follow-up was complete except for one patient, who was no longer available for follow-up 4 years after operation. Eleven patients (7.6%) had a second primary cancer in the lung; 10 of these patients (90.9%) were men. Mean age at sleeve operation was 61.2 +/- 11.6 years. Mean interval between sleeve operation and development of second primary cancer was 53.8 months (range, 6 to 197 months). All second primary cancers occurred on the contralateral side. In five cases there was squamous cell carcinoma, in two there was adenocarcinoma, in one there was adenosquamous carcinoma, in two there was small cell carcinoma, and in one patient no definite histologic type could be established. Five patients had different histologic type from the initial, resected primary tumor. Seven patients (64%) were operated on: five underwent lobectomy and two underwent segmentectomy. In one patient the tumor was judged to be unresectable. Chemotherapy was given to the two patients with small cell carcinoma and radiotherapy was given to one patient with bone metastases. Follow-up was complete for these 11 patients. Data were calculated from detection of second primary cancer. There was one postoperative death from myocardial infarction. Eight other patients died during follow-up: five died of recurrent tumor or metastases, two died of acute cardiac failure, and one died of a perforated ulcer. The 1- and 4-year actuarial survivals were 41% and 30%, respectively. For the patients operated on, 1- and 4-year survivals were 57% and 43%, respectively. There were no survivors at 5 years. Sleeve resection is a valuable method of preserving functional lung tissue. It offers a chance of subsequent resection in patients who have second primary cancer, with acceptable results. PMID- 1434730 TI - Bronchopleural fistulas associated with lung cancer operations. Univariate and multivariate analysis of risk factors, management, and outcome. AB - During a 28-year period, 52 bronchopleural fistulas developed after pulmonary resection of 49 primary and three recurrent lung cancers at the National Cancer Center Hospital, Tokyo. During the same period there were 2359 pulmonary resections for primary lung cancer; the prevalence of bronchopleural fistula was 2.1%. Multivariate analysis on 15 variables in the most recent 1360 resections revealed significant risk factors for bronchopleural fistula: wider resection such as pneumonectomy, residual carcinomatous tissue at the bronchial stump, preoperative irradiation, and diabetes. Univariate analysis further recognized a risk in preoperative bronchial arterial infusion and the postsurgical stage of lung cancer. Six patients were not treated. Apart from chest tube drainage in seven patients, surgical repair was attempted in 39, direct resuture of the stump in 16, wrapping in 25, thoracoplasty in 31, completion pneumonectomy in 6, and other treatments. Despite various treatments, 37 patients (71.2% mortality) died from fistula-related complications (such as regurgitation of infected pleural fluid through the fistula and airway/intrathoracic bleeding). Even for patients whose fistulas were cured and who were discharged, the average hospital stay was 189 days. Further investigation is necessary to answer whether prevention by flap coverage is of any benefit. PMID- 1434731 TI - A twenty-five-year follow-up of ninety-three resected typical carcinoid tumors of the lung. AB - From 1965 to 1990, 93 patients (57 women and 36 men) with typical bronchopulmonary carcinoids were operated upon. Patient ages ranged from 17 to 78 years, the mean age being 45.5 years. Central carcinoids were symptomatic in 80% of the patients. A correct preoperative diagnosis was made in 54 of 64 (84%) patients. Peripheral carcinoids were usually asymptomatic and a correct diagnosis was established in 4 of 29 patients (14%). The prognosis in the group of patients with bronchopulmonary carcinoids treated surgically was excellent. Seven patients died from nonrelated causes. The 5-, 10-, and 15-year survival rates for the remaining 86 patients are 100%. Only one patient died as a result of the tumor after 17 years and another patient is known to have had distant metastasis 9 years after resection. There was no hospital mortality. In the last decade a lung parenchyma-preserving attitude was adopted. Whenever possible, bronchoplastic surgery was applied for central carcinoids and resection of one segment or less was used for peripheral carcinoids. This approach was possible in 30 of 50 patients (60%). Nine patients were treated with preoperative endobronchial neodymium:yttrium-aluminum-garnet laser resection to facilitate a lung-preserving surgical resection. The prognosis of patients for whom a lung-preserving approach was adopted was as good as that of those with conventional resections. Involvement of regional lymph nodes (nine patients, 9.7%) or positive resection margins (two patients, 2.1%) had no influence on prognosis. We conclude that lung preserving resections are often facilitated by preoperative neodymium:yttrium aluminum-garnet laser treatment in central obstructing carcinoids. PMID- 1434732 TI - Degree of severity of pectus excavatum and pulmonary function in preoperative and postoperative periods. AB - Pulmonary function was evaluated in 138 patients with pectus excavatum, paying particular attention to the degree of severity of chest deformity. We defined the severity of deformity quantitatively based upon a computed tomographic index obtained from a computed tomogram. We recognized a positive relationship between computed tomographic index (x) and percent vital capacity (y), as follows: y = 137x + 58 (n = 138, r = 0.61, p < 0.05). Pulmonary function tests were performed from 2 to 42 months postoperatively. Vital capacity decreased about 10% from the baseline value during the initial 2 months after surgical treatment and recovered to the preoperative level by 1 year after surgery. At 42 months after surgical correction, the pulmonary function was maintained at the baseline level and the severity of deformity was significantly improved. Surgical procedures for the treatment of pectus excavatum--sternocostal elevation and sternal turnover- resulted in an excellent cosmetic result but did not importantly affect respiratory function. PMID- 1434733 TI - Invited letter concerning: correction of prolapse of the anterior leaflet of the mitral valve. PMID- 1434734 TI - Possible treatment for meralgia paresthetica after coronary bypass operations. PMID- 1434735 TI - Surgical treatment of atrial fibrillation. PMID- 1434736 TI - Invited letter concerning: futility of yearly biopsies in patients undergoing heart transplantation. PMID- 1434737 TI - Ebstein's anomaly and intermediate-form atrioventricular septal defect with double-orifice mitral valve. PMID- 1434738 TI - Surgical repair of Ebstein's malformation associated with atrioventricular septal defect (atrioventricular canal). PMID- 1434739 TI - Echocardiographic assessment of homograft aortic root replacement in fixed subaortic stenosis. PMID- 1434740 TI - Subtotal cavopulmonary connection. PMID- 1434741 TI - The dioxopiperazine derivatives, their leukemogenic potential and other biological effects. PMID- 1434742 TI - Interactions between retroviruses and environmental carcinogens and their role in animal and human leukemogenesis. PMID- 1434743 TI - Relationship of the type of bcr-abl hybrid mRNA to clinical course and transforming activity in Philadelphia-positive chronic myelogenous leukemia. AB - We studied the type of bcr-abl mRNA for 34 patients with chronic myelogenous leukemia and analyzed for correlations among the mRNA type, the clinical outcome and the transforming activity using the tumorigenicity assay. There was no difference in the distribution of the mRNA-types (b2-a2 and b3-a2) between clinical phases. We found no correlation between the two types of bcr-abl mRNA and the chronic phase duration or survival. The DNA from 12 of 20 chronic phase patients and all five blastic phase patients showed transforming activity. Although there was no difference in the positive rate of transforming activity among the two mRNA-type groups, the blastic phase patients showed a tendency to have higher transforming activity. PMID- 1434744 TI - Unexpected cytokinetic effects induced by puromycin include a G2-arrest, a metaphase-mitotic-arrest, and apoptosis. AB - The potent effects of low doses of PM on the cell cycle have to date been obscured by the conventional usage of this drug at high concentrations (5-50 micrograms/ml) to inhibit protein synthesis. In this in vitro study undertaken in a variety of malignant and non-malignant human and murine cell types, we found that low doses of PM (0.1-0.5 microgram/ml) disrupted significant phase-to-phase cell cycle transitions, causing a G2-arrest, a metaphase-mitotic-arrest, and apoptosis. In HL-60 cells these observations were elicited by PM concentrations starting at 0.1 microgram/ml, and were more pronounced at slightly higher PM concentrations, including that (0.5 microgram/ml) which inhibited [14C]leucine incorporation by approximately 20% after one hour, and by approximately 50% after 24 h. A concentration of CHX (0.25 microgram/ml) which was equivalent to 0.5 microgram/ml of PM, both in terms of molarity (0.9 microM) and degree of inhibition of [14C]leucine incorporation, failed to induce similar changes to those induced by PM. This suggests that at these particular concentrations the PM induced changes were likely to have been related to the different mechanisms of protein synthesis inhibition exerted by these two 'classical' translation inhibitors. PM but not CHX generates nascent peptidyl-PM complexes (PMPs), and we therefore propose that the subsequent intracellular effects exerted by the PMPs may account, in part, for the differential cytokinetic effects elicited by these drugs. The role of PM is currently being evaluated in vivo as a low-dose component of a multidrug chemotherapeutic regimen in which its cell cycle specific effects could potentially be synergistic with other agents. PMID- 1434745 TI - Immunological studies of gamma delta T cells in a case of large granular lymphocyte (LGL) leukemia: leukemic gamma delta+ T cells are resistant to growth stimulation in vitro but respond to interferon-alpha treatment in vivo. AB - Leukemic T cells from patient BU (WBC 22,000/microliter) resembled morphologically large granular lymphocytes, and expressed a V delta 1-encoded gamma delta T-cell receptor (TCR) on their surface. Upon in vitro activation with various mitogens, IL-2-dependent V delta 1+ cell lines were only obtained if V delta 1+ cells had been positively selected on a cell sorter before culture. However, even under these conditions, the V delta 1+ IL-2-dependent cell lines showed a TCR beta and gamma gene-rearrangement different from that of the freshly isolated leukemic cell population, indicating that they were not derived from the leukemic clone. Thus, known T-cell growth factors (IL-2, IL-4, IL-7) in concert with mitogenic signals failed to induce in vitro proliferation of the V delta 1+ leukemic clone. Interestingly, the patient responded to treatment with interferon alpha 2c (daily dose of 10(6) I.U.). After 2 1/2 years of continuous interferon treatment, the patient is in partial remission with WBC around 8000/microliter. PMID- 1434746 TI - Modification of the DiSC assay by the incorporation of monoclonal antibody staining. AB - The use of immunohistochemical staining with the DiSC assay is described. This modified staining procedure allows differentiation of viable human tumor cells from normal cells in biopsy preparations, facilitating the evaluation of slides from chemosensitivity assays. Samples from ALL and CLL patients were processed using both the DiSC and modified MoAb-DiSC procedure. The predictive results were compared and found to be identical. This procedure is advantageous in determining the chemosensitivity of tumor cells in a highly heterogeneous biopsy specimen. PMID- 1434747 TI - Specific chromosomal translocations and therapy-related leukemia induced by bimolane therapy for psoriasis. AB - This paper reports for the first time results of cytogenetic studies on 14 consecutive secondary acute non-lymphocytic leukemia (S-ANLL) induced by bimolane therapy. They included 10 males and 4 females with ages ranging from 17 to 54 years. They had all suffered from psoriasis and received bimolane treatment before the occurrence of their leukemia. The total dose of bimolane ranged from 40 to 400 g (mean dose 194 g). The interval between the initiation of bimolane therapy and the diagnosis of leukemia was 12-96 months (median 30 months). A preleukemic phase was only found in one case. No dysplastic features in the hemopoietic series were seen in any patient. Chromosome analysis of bone marrow cells using banding techniques revealed clonal karyotypic abnormalities in all cases: t(15;17) in 8 cases of M3, of which 75% had extra abnormalities, t(8;21) in 4 cases of M2, del(7q) only in one case of M4 and one case of M5. After antileukemic therapy, complete remission was obtained in 10 out of 12 cases with specific translocations and one out of 2 cases with 7q-anomaly, respectively. The former survived 4-58 months (median 12 months), while the latter 1 and 9 months, respectively. This study indicates that: (1) bimolane is a causative factor of leukemia in this series; (2) the leukemia in our series is therapy-related leukemia (TRL) rather than de novo ANLL; (3) there exists, in fact, a new subgroup of TRL characterized by specific rearrangements, whose clinical, hematological and prognostic features and pathogenetic mechanism may be different from classical TRL characterized by chromosome abnormalities involving absence or deletion of parts of chromosome 5 and/or 7. PMID- 1434748 TI - HTLV-related markers in a Hungarian patient with adult T-cell leukemia. AB - Monoclonal integration of DNA sequences related to, but not identical to HTLV-I provirus was detected in the peripheral blood lymphocytes of a Hungarian male suffering from ATL. The patient and his parents showed serological cross reactivity with both HTLV-I and HTLV-II group-specific antigens. Restriction enzyme analysis with EcoRI, PstI, BamHI, HindIII and SacI revealed structural similarity of the provirus integrated in the DNA of ATL cells to HTLV-I but not to HTLV-II. Data suggest that this provirus and HTLV-I are similar to each other along gag and pol regions, but they are different in the env region. PMID- 1434749 TI - A new method of mounting and directing chronically implanted microdrives. AB - A new method of mounting a microdrive on the skull and adjusting the trajectories of microelectrodes is described. The key to this system is a swiveling guide tube held in a small, skull-mounted base by a low-melting-point metal alloy. The microelectrode is advanced via a modified, commercially available, miniature microdrive screwed onto the guide tube. To change the trajectory of the electrode, the alloy is melted in place, and the guide tube swiveled to a different angle. The microelectrode or the trajectory of the pass may be changed in a few minutes while easily maintaining aseptic conditions. The entire assembly is small enough so that several can be simultaneously implanted on the skull of a cat. A metal crown is used to fix the head during recording sessions or to hold a fiberglass cap that protects all skull implants between sessions. Since the microdrives need not be removed between recording sessions, an electrode pass may be continued from day to day. Although guide tubes are generally employed only for subcortical structures, this arrangement also works well when recording from cortex in deeper parts of gyri. PMID- 1434750 TI - Positioning device for magnetically sensitive environments. AB - Presented in this short communication are design principles for the construction of a positioning apparatus for biological specimens in magnetically sensitive environments. An apparatus with 3 degrees of freedom was built and found to provide position accuracy to within +/- 0.25 mm throughout a cubic volume measuring 9 cm on each side. PMID- 1434751 TI - Purification of embryonic rat motoneurons by panning on a monoclonal antibody to the low-affinity NGF receptor. AB - Available methods for purifying motoneurons to homogeneity from rodent spinal cord involve retrograde labelling and fluorescence-activated cell sorting, making them costly and time consuming. Motoneurons are the only neurons within the 15 day embryonic rat spinal cord to express the p75 low-affinity NGF receptor and we show that monoclonal antibody 192-IgG, which binds to the extracellular domain of p75, selectively labels a sub-population of large multipolar ventral spinal cord neurons in vitro. We have developed a bench-top panning method for purifying these motoneurons using antibody 192-IgG. Approximately 10(5) cells/spinal cord are obtained in 2 h by this method; 95% of them express p75 in culture. They rapidly put out neurites on laminin substrata, and their survival is enhanced by extracts of skeletal muscle. Using the panning method in conjunction with centrifugation on a 6.8% metrizamide cushion, separate populations of large and small motoneurons were obtained, each containing more than 90% neurons staining with antibody 192. The large motoneurons had choline acetyltransferase activities/cell approximately 4-fold greater than those of dissociated total spinal cells and 7-fold higher than those of the small motoneurons. These methods should be of considerable use for studies on factors affecting motoneuron survival and development and for transplantation of highly purified neuronal populations. PMID- 1434752 TI - Fluorescent labeling of dissociated fetal cells for tissue culture. AB - The ability to pre-label cells used in transplantation experiments would have the potential benefits of identification of cell type and associated processes and the analysis of graft migration in the host. We have used an in vitro tissue culture system as a model to test several fluorescent dyes for this application. Fetal rat hippocampal tissue (E17-E18) was dissociated and incubated in the presence of carboxyfluorescein ester (CFSE), rhodamine-B dextran amine (RBD), DiI, or rhodamine-labeled latex microspheres. Cells were cultured in defined medium for up to 1 month. Cells labeled with CFSE were initially bright but faded over several days. RBD labeled the soma of cells, but fluorescence intensity was lost over a period of a few weeks. Cells labeled with DiI possessed brilliant staining of neuronal processes for weeks. Latex microspheres brightly labeled the soma but not the processes of neurons; fluorescent debris and sterility were problems with this label. We conclude that CFSE and DiI have significant potential usefulness in vitro as markers of cell viability and process formation with mammalian fetal CNS cells, whereas RBD is much less permanent. Latex microspheres may be suitable for pre-labeling of cells for transplantation if purification and sterility can be enhanced over present preparations. PMID- 1434753 TI - A gated differential amplifier for recording physiological responses to electrical stimulation. AB - Artifact from electrical stimulation imposes a problem for the recording of physiological responses to electrical stimulation. Here we describe a simple, low cost, gated differential amplifier for the recording of physiological responses to electrical stimulation. The gain of the amplifier is set to 1 during electrical stimulation by setting the gate input to a high logic state to avoid overloading of the amplifier by the artifact. Following electrical stimulation, the gate input is set to a low logic state, resulting in a gain of 1000 for frequencies between 300 Hz and 25 kHz (-3 dB points). The gain at low frequencies (0-0.2 Hz) is held constant at 1 to avoid transients in the output signal arising from changes in gain at these frequencies. The gain of the amplifier following stimulation (gate low) was independent of the magnitude of the artifact and was therefore suitable for the measurement of neural field potentials with low impedance electrodes. PMID- 1434754 TI - Antiprogestin drugs: ethical, legal and medical issues. PMID- 1434755 TI - Updating RU 486 development. PMID- 1434756 TI - Antiprogestin drugs: research and clinical use in Sweden. AB - The Swedish experience indicates that the combination of RU 486 and vaginal or intramuscular administration of different prostaglandin analogues such as Cervagem, Sulprostone, and 15- methyl PGF2 alpha is a highly effective and safe non-surgical method to terminate early pregnancy. The combined treatment may also be used during the second trimester. In mid- and late second trimester abortion this procedure represents a simple, non-invasive, highly effective method. There are several possibilities by which RU 486 can be used as a contraceptive. We have shown that post-ovulatory administration of RU 486 will effectively inhibit implantation. If the preliminary results are confirmed, treatment with RU 486 once a month on day LH+2 may be an attractive alternative to present contraceptive technology. PMID- 1434757 TI - Introduction of abortion technologies: a quality of care management approach. PMID- 1434758 TI - RU 486/prostaglandin: considerations for appropriate use in low-resource settings. PMID- 1434759 TI - RU 486: what physicians know, think and (might) do--a survey of California obstetrician/gynecologists. AB - The results of this informal survey indicate that a solid majority of California obstetricians and gynecologists are very interested in RU 486 and are following its story closely; that this majority is confident in the research already conducted on the drug, and feel that RU 486 should be made available at this time for both clinical practice and additional research; that many physicians already performing abortions would utilize RU 486 in their practices; and that a significant number of physicians not currently performing abortions would do so using RU 486, thus potentially increasing access to early abortion services in this country. However, strong support for RU 486 among American physicians has not yet had an appreciable impact on hastening the eventual availability of RU 486 in the United States. PMID- 1434760 TI - Studying the acceptability and feasibility of medical abortion. PMID- 1434761 TI - "Inducing a miscarriage": women-centered perspectives on RU 486/prostaglandin as an early abortion method. PMID- 1434762 TI - Are adolescents good candidates for RU 486 as an abortion method? PMID- 1434763 TI - Antiprogestin drugs: ethical issues. PMID- 1434764 TI - Do pharmacists have a right to refuse to fill prescriptions for abortifacient drugs? PMID- 1434765 TI - RU 486, the FDA and free enterprise. PMID- 1434767 TI - Patents and the supply of therapeutic products. PMID- 1434766 TI - RU 486 in France and England: corporate ethics and compulsory licensing. PMID- 1434768 TI - Benten v. Kessler: the RU 486 import case. PMID- 1434769 TI - Abortion on the Supreme Court agenda: Planned Parenthood v. Casey and its possible consequences. PMID- 1434771 TI - The FDA: is it protecting the public with one hand tied behind its back? PMID- 1434770 TI - Patient dumping in the federal courts: expanding EMTALA without preempting state malpractice law. PMID- 1434772 TI - Capping the crisis: medical malpractice and tort reform. PMID- 1434773 TI - Hospital did not commit battery on mortician who embalmed HIV-infected corpse. PMID- 1434774 TI - OSHA issues regulations on workplace exposure to bloodborne pathogens. PMID- 1434775 TI - Patient stories, doctor stories, and true stories: a cautionary reading. PMID- 1434776 TI - Charting Dante: the Inferno and medical education. PMID- 1434777 TI - Seeing patients. PMID- 1434778 TI - Tragedy of the commonplace: the impact of addiction on families in the fiction of Thomas Hardy. PMID- 1434779 TI - The fall of John Thomas. PMID- 1434780 TI - Beloved illness: transference love as romantic pathology in F. Scott Fitzgerald's Tender is the night. PMID- 1434782 TI - Self-administered chest physiotherapy in cystic fibrosis: a comparative study of high-pressure PEP and autogenic drainage. AB - Fourteen patients with cystic fibrosis were trained in 2 self-administered chest physiotherapy (PT) techniques: high-pressure PEP-mask physiotherapy (PEP), and autogenic drainage (AD). They then visited the clinic on 5 consecutive days, and, in a random order, performed 1 of the following: PEP, AD, PEP followed by AD (PEP AD), AD followed by PEP (AD-PEP), and, no PT except for spontaneous coughing. Lung function was measured repeatedly before, during, and after PT; time needed for and sputum produced by each form of PT was recorded. PEP produced the highest amount of sputum, followed by PEP-AD, AD-PEP, and AD; all 4 forms of PT produced significantly more sputum than coughing. Lung function improved significantly after PEP, AD, and PEP-AD, but PEP-induced changes did not exceed those after AD. Within the investigated group, the PEP-induced lung function improvement per milliliter of sputum produced was significantly lower for those patients with airway hyperreactivity. The fact that the highest sputum yield with PEP was not reflected in higher PEP-effected lung function changes might thus be explained by PEP-induced bronchospasm in patients with airway hyperreactivity. PEP clears more sputum than AD or combined techniques; patients with airway hyperreactivity, however, should either prefer AD or should take a bronchodilator premedication before PEP. PMID- 1434781 TI - Combined effects of ozone and cigarette smoke on airway responsiveness and vascular permeability in guinea pigs. AB - The effects of combined exposure to ozone and cigarette smoke on airway responsiveness and tracheal vascular permeability, compared with those of single exposure were examined in guinea pigs. Airway responsiveness was assessed by measuring the specific airway resistance (sRaw) as a function of increasing concentration of inhaled methacholine aerosol immediately, 5 hr, and 24 hr after exposure. In a parallel study, tracheal vascular permeability was quantified by measuring the tracheal extravasation of intravenously administered Evans blue dye. Neither exposure to 1 ppm ozone for 30 min nor 5 puffs of cigarette smoke increased airway responsiveness or vascular permeability at any time after exposure. Combined exposure to 1 ppm ozone for 30 min and 5 puffs of cigarette smoke caused airway hyper-responsiveness and increased vascular permeability immediately after exposure. Exposure to 1 ppm ozone for 90 min increased both airway responsiveness and vascular permeability immediately after exposure. Exposure to 10 puffs of cigarette smoke increased airway responsiveness but not vascular permeability immediately after exposure. Combined exposure to 1 ppm ozone for 90 min and 10 puffs of cigarette smoke increased both airway responsiveness and vascular permeability immediately after exposure. The combined exposure to ozone and cigarette smoke thus increased both airway responsiveness and tracheal vascular permeability to a greater extent than did exposure to a single agent, suggesting that a combination of air pollutants has a more deleterious effect both on airway responsiveness and on tracheal vascular permeability than does either agent alone in guinea pigs. PMID- 1434783 TI - Cellular sequence of tracheal repair in sheep after smoke inhalation injury. AB - The cellular repair process of injured tracheal epithelium is described for sheep after exposure to toxic smoke containing high concentrations of acrolein. Fourteen fasted 3-4-year-old ewes had a portion of their cervical trachea exposed to cotton smoke for 20 min and then were sacrificed at various time intervals ranging from 1 to 22 days after exposure. Within 1 day of injury, columnar epithelium sloughed intact from the trachea with a concomitant reduction of nearly 35% in the basal cell population. At 2 days of recovery, the cellularity of the epithelium had increased and mitotic figures were observed in some tracheal epithelial and gland cells. By 8 days, undifferentiated hyperplastic cells increased to 30/100 microns, differentiated nonciliated columnar cells first appeared, and the basal cell population returned to a normal count of 13 cells/100 microns. Thirteen days after exposure, the undifferentiated hyperplastic cell population had declined to 7 cells/100 microns, nonciliated columnar cells were at control values, and some ciliated cells were identified. At 18 and 22 days, epithelium was normal in appearance and the count was 13 cells/100 microns. Data suggest that because the columnar epithelium sloughs intact with the cilia remaining active, toxic smoke may affect their attachment to the basal lamina. Furthermore, the regeneration process involves differentiation of hyperplastic cells in which they elongate down to the basal lamina, thus re-establishing the integrity of tall epithelium in the sheep trachea. PMID- 1434784 TI - Hypotonic solutions induce epithelium-dependent relaxation of isolated canine bronchi. AB - The present study was designed to investigate the effect of changes in osmolarity on the modulatory role of the respiratory epithelium on the underlying smooth muscle. Canine bronchial segments with or without epithelium were perfused intraluminally with modified Krebs-Ringer bicarbonate solution. The transluminal isometric tension was recorded by means of stirrups passed through the bronchial wall. During contractions to extraluminal carbachol, the tissues with epithelium exhibited epithelium-dependent relaxations to hypotonic solution given intraluminally. The level of relaxation was dependent on the osmotic pressure. No significant difference was noted between relaxations due to hypotonic solution made by mixing the Krebs-Ringer solution with distilled water and those made by decreasing the concentration of sodium chloride. The epithelium-dependent relaxations could not be blocked by the antagonists or blockers of cyclo oxygenase, endothelium-derived relaxing factor, alpha-adrenoceptors, beta adrenoceptors, and sodium channels. No evidence for the release of a relaxing factor into the bronchial lumen was found in bioassay study. When the preparation was stimulated with hypertonic solutions prepared by adding mannitol or urea, similar relaxations were induced in tissues with and without epithelium. These observations suggest that changes in osmolarity affect the responses of canine bronchi to carbachol and that the epithelium modulates the responses of airway to hypotonic solutions. PMID- 1434785 TI - Spontaneous cluster formation of dendritic (veiled) cells and lymphocytes from skin lymph obtained from dogs with chronic lymphedema. AB - To examine the mechanism of spontaneous attachment of afferent lymph lymphocytes to dendritic cells (veiled), we sampled and tested cells from skin lymph in 3 dogs with chronic lymphedema. There were 3.3 +/- 2.8% veiled cells in clusters with lymphocytes in lymph obtained directly from dilated dermal lymphatics by percutaneous puncture. The number of ex vivo clusters forming in the collected lymph samples increased as a function of time and was temperature dependent. The ability of veiled cells to bind lymphocytes was independent of divalent cations but reduced by xylocaine and retinoic acid. Among various steroids tested only methylprednisolone showed an inhibitory effect on cluster formation. Indomethacin and acetylsalicylic acid had no blocking activity on cell binding. Moreover, no effect was seen by cyclosporin A and azathioprine. However, FK 506 had a potent inhibitory effect on spontaneous cluster formation. This study suggests that cluster formation by skin lymph veiled cells and lymphocytes is a spontaneous process which can be controlled in vitro. PMID- 1434786 TI - Enhancement of cytotoxicity in mouse regional lymph nodes by local tissue injection of aclacinomycin A. AB - The effect of local tissue injection of activated carbon particle adsorbing aclacinomycin A (ACR-CH) on the cytotoxicity in popliteal, inguinal, paraaortic, and axillary lymph nodes was investigated in mice. Aclacinomycin (0.2 mg/kg), a potent antineoplastic drug was injected subcutaneously into the footpad of mice in the form of ACR-CH or as an ACR solution. After a single injection of ACR-CH, the regional nodal cytotoxic response against mouse YAC-1 lymphoma cells was markedly increased and sustained for 7-10 days. The immune response was also increased after ACR solution but to a much lesser extent. These effects were found in popliteal, inguinal, and paraaortic lymph nodal effector cells but not in the more remote axillary nodes. Absorption of adherence cells largely abrogated the cytotoxic response. These results suggest that ACR-CH did not impair but rather stimulated nodal immunoregulatory cells. Potentially ACR-CH may enhance immune responsiveness of regional lymph nodes after subcutaneous administration while concomitantly curtailing neoplastic growth in these same lymph nodes. PMID- 1434787 TI - Particle clearance from the canine pleural space into thoracic lymph nodes: an experimental study. AB - We instilled tungsten powder (CaWO4) into the pleural space of the dog and studied the kinetics and distribution of particle translocation from the pleural space to the thoracic lymph nodes over 1-7 days. We found that the transport of tungsten particles to regional lymph nodes was present at day 1, and reached its peak at day 3. In situ detection of tungsten by elemental particle analysis of lymph node sections by scanning electron microscopy complemented by light microscopy and X-ray analysis allowed precise mapping of the marker in the thoracic nodes. The first lymph nodes to become tungsten-laden was the parasternal group (day 1-3). From day 3 to 7 tungsten inclusions decreased in these parasternal nodes while moderately increasing in the remaining intrathoracic lymph nodes. Retrocardiac pleural folds containing numerous "milky spots" also accumulated prominent amounts of tungsten early after intrapleural injection of CaWO4. These data indicate that 1) particle translocation from the pleural space to regional lymph nodes is a rapid process and is first directed to the parasternal lymph nodal subgroup; 2) particle dissemination to virtually all other lymph nodes within the thorax follows thereafter; 3) retrocardiac pleural folds contribute to the clearance of particles from the pleural space. PMID- 1434788 TI - Ultrasonography of extremity lymphedema. AB - Ultrasonography of the extremities was performed in 91 patients with unilateral or bilateral peripheral lymphedema of the arms or legs. Linear 3.5 to 10 mHz ultrasonographic linear probes were used in accordance with standardized procedure. The data demonstrated a volumetric increase of the lymphedematous limb with increased thickness of both the subcutaneous and subfascial (muscular) compartments consistent with fibrosclerosis in both compartments with chronic disease. Whereas dermal thickening was minimal, subcutaneous and subfascial changes were more prominent in primary than secondary lymphedema. By providing information about the volumetric and structural alterations with chronic lymphedema, ultrasonography safely and simply supplements conventional and isotopic lymphography in assessing patients with chronic lymphedema. PMID- 1434789 TI - Mesenteric lymph node transplantation in syngeneic rats: changes in cellularity and architecture. AB - The cellular architectural and functional changes of transplanted mesenteric lymph nodes in rats were studied. After lymph nodes were transplanted with interruption of both the afferent and efferent lymphatics, the nodal cellular content gradually became depleted. One month after operation, the recirculating lymphocyte count in the transplanted node was only 3.5% of that in control nodes, whereas the number of mononuclear cells per mg tissue of transplanted node was only 28% of normal. In the transplanted nodal paracortex, the cells of high endothelial venules (HEV) became less prominent and gradually flattened altogether. In the transplanted nodal cortex, germinal centers and follicles also sharply decreased and later disappeared. Three months after transplantation, the normal compartmentalization of the transplanted nodes were no longer distinguishable. Regeneration of afferent lymphatics was not detected in transplanted nodes and the lack of circulating antigen and stimulated lymphocytes was probably responsible for the histological and functional involution of grafted mesenteric lymph nodes. PMID- 1434790 TI - Detection of relapse in acute leukemia: should we discontinue routine bone marrow surveillance? PMID- 1434791 TI - Autologous bone marrow transplantation in acute myelogenous leukemia. AB - Autologous bone marrow transplantation (ABMT) is a therapeutic approach that permits the administration of high-dose chemoradiotherapy followed by the infusion of the patient's own marrow, previously collected during remission and cryopreserved. In recent years, ABMT has been increasingly used as a treatment for acute leukemias. The mechanisms underlying leukemic relapse represent the most exciting and controversial aspects of ABMT. At least three factors may be responsible for leukemic relapse in patients receiving ABMT: (a) minimal residual disease; (b) leukemic cells reinfused with the graft; and (c) the lack of a graft versus-leukemia effect. Techniques for pharmacological marrow decontamination, clinical results obtained with ABMT, and new perspectives opened by growth factors and cytokines are reviewed. PMID- 1434792 TI - Antibody recognition of the tumor-specific b3-a2 junction of bcr-abl chimeric proteins in Philadelphia-chromosome-positive leukemias. AB - The reciprocal translocation between chromosome 9 and chromosome 22, as observed in chronic myeloid leukemia (CML) as well as in acute lymphoblastic leukemia (ALL), results in a 22q- chromosome, the so-called Philadelphia chromosome. The translocation event creates on the Philadelphia chromosome a fusion between two genes: bcr and abl. Depending on the localization of the breakpoint in the bcr gene different chimeric bcr-abl genes are generated, each encoding their own tumor-specific protein: e1-a2P190bcr-abl, b2-a2p210bcr-abl, or b3-a2P210bcr-abl. Especially in ALL, the presence of such a tumor-specific protein is highly associated with a poor prognosis. Detection of these proteins therefore has a strong clinical significance. In this study a polyclonal antiserum, termed BP-2, was raised against a synthetic peptide, corresponding to the tumor-specific 'fusion-point' epitope of the b3-a2P210bcr-abl protein. The specificity of BP-2 for the bcr-abl joining region in b3-a2P210bcr-abl is demonstrated by means of peptide inhibition studies in combination with immunoprecipitation. In addition we show the reactivity of BP-2 with bcr-abl proteins in leukemic cells of a Philadelphia-chromosome-positive ALL patient. PMID- 1434793 TI - Feasibility of the fluorometric microculture cytotoxicity assay (FMCA) for cytotoxic drug sensitivity testing of tumor cells from patients with acute lymphoblastic leukemia. AB - The automated fluorometric microculture cytotoxicity assay (FMCA) was used for chemotherapeutic drug sensitivity testing of fresh and cryopreserved tumor cells from patients with acute lymphoblastic leukemia (ALL) at diagnosis and relapse. The technique success rate was 87% for fresh and 81% for cryopreserved samples. Up to 16 different cytotoxic drugs were routinely tested, but neither asparaginase nor methotrexate produced dose-response related cell kill. FMCA data showed good correlation to the well established Disc assay and the drug sensitivity reported by the FMCA was in good agreement with known clinical activity. Samples from children and initial ALL tended to be more drug sensitive than those from adults and ALL at relapse, respectively. For 36 samples clinical outcome was correlated to the quartile position in comparison to all other samples for the most in vitro active drug actually given to the patient. For patients with samples in the first, second, third, and fourth quartiles, the probabilities of complete remission were 89, 57, 38, and 0%, respectively. Using the median value as cut-off line, the sensitivity and specificity of the assay were 87 and 62%, respectively. It is concluded that the FMCA with a minimum of effort and with high success rate report clinically relevant drug sensitivity profiles for ALL. PMID- 1434794 TI - Differences in DNA fingerprints of continuous leukemia-lymphoma cell lines from different sources. AB - The genetic stability of human cell lines in long-term culture has been tested by DNA fingerprinting a panel of 31 different continuous cell lines from patients with leukemias or lymphomas. Duplicates of the same cell line obtained from different sources, subclones of cell lines, and samples of cell lines at different passage levels were studied. In most cases the fingerprints of duplicates of the same cell line remained perfectly preserved even after long time passaging. However, in five cases there were notable differences between individual fragments of corresponding fingerprints. We have found four cases of mislabeled and/or cross-contaminated cell lines so far. Taken together, our results indicate that DNA fingerprinting qualifies as a very reliable means of cell line identification which allows the detection of mislabelling or contamination and of genetic variation among subclones. PMID- 1434795 TI - Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells. AB - Insulin and the insulin-like growth factors (IGF-I, IGF-II) constitute a family of peptides capable of stimulating diverse cellular responses, including cell proliferation. In order to determine the effects of these peptides on malignant cells, we analyzed the expression and function of insulin, IGF-I, and IGF-II receptors on B-cell precursor acute lymphoblastic leukemia (BCP ALL) cell lines, utilizing competitive binding, affinity crosslinking, and cell proliferation assays. The BCP ALL cells bound to each peptide with mean specific binding for 125I-insulin, 125I-IGF-I, and 125I-IGF-II of 19.6%, 7.1%, and 4.3% of radioligand added, respectively. Competitive binding to intact cells demonstrated that 125I IGF-I was displaced by IGF-I = IGF-II >> insulin, 125I-IGF-II was displaced by IGF-II > insulin = IGF-I, and 125I-insulin was displaced by insulin >> IGF-II > IGF-I. These data were remarkable for the potency of IGF-II displacement of 125I IGF-I and 125I-insulin. Affinity crosslinking of radioligands to SUP-B2 cell membranes demonstrated the high affinity insulin and IGF-I (type 1 IGF) receptors. IGF binding proteins were also present in BCP ALL cell membrane preparations. In the cell proliferation studies, insulin stimulated a 50-130% increase in leukemic cell growth with a half-maximal concentration of 0.1-3.0 ng/ml in three BCP ALL cell lines. The proliferative response to insulin was blocked by the addition of an insulin receptor antibody. However, no response was observed with IGF-I, and IGF-II was only weakly mitogenic with a proliferative response noted at 100 ng/ml. Thus, while BCP ALL cells possess receptors for insulin and IGF-I, only the insulin receptor mediated a proliferative response. PMID- 1434796 TI - Expression of the serglycin gene in human leukemic cell lines. AB - The expression of the human serglycin gene was determined in nine human leukemic cell lines, representing a spectrum of erythrocytic, megakaryocytic, monocytic, granulocytic, and lymphocytic potentialities. By Northern blot analysis, a 1.4 kb transcript was characterized in some of these cell lines, using a cDNA probe coding for human serglycin. Five of these cell lines, HEL, U-937, HL-60, K-562, and KU-812 were treated with phorbol myristic acetate to induce differentiation. Under these conditions the expression of the serglycin gene was modulated compared to the non-induced cells. HL-60, K-562, and KU-812 were also induced with dimethyl sulfoxide and retinoic acid; variations in serglycin transcript level were also observed. The present investigation establishes, at the nucleic acid level, the ability of various cells mimicking different stages in the developmental pathways of the haemopoietic lineage to synthesize proteoglycans belonging to the serglycin family. The results reported here led us to conclude that serglycin expression is closely associated with the haemopoietic cell differentiation pathway. The putative functions of serglycin in the haemopoietic system are briefly discussed. PMID- 1434797 TI - Production of tumor necrosis factor-alpha in human long-term marrow cultures from normal subjects and patients with acute myelogenous leukemia: effect of recombinant macrophage colony-stimulating factor. AB - We have recently reported that normal long-term marrow cultures (LTMC) treated with recombinant human macrophage colony-stimulating factor (rhCSF-1), as well as LTMC from patients with acute myelogenous leukemia (AML), produce a soluble activity capable of inhibiting hemopoietic colony formation in semisolid cultures. In the present study, we have found that such an activity is produced, both in normal and AML LTMC, by an adherent, nonfibroblastic cell population (most likely macrophages), and also by blast cells developed in AML LTMC. The presence of the inhibitory activity correlated with increased levels of tumor necrosis factor (TNF) in the culture supernatants. Part of the activity (30%) produced in rhCSF-1-treated normal LTMC was neutralized in colony assays by anti TNF alpha monoclonal antibody. In contrast, the soluble inhibitory activity from AML LTMC was completely neutralized by anti-TNF alpha. However, addition of anti TNF alpha (every 72 h, from day 0 to 21, at 125 ng/ml) to AML LTMC resulted in only partial neutralization of the inhibitory activity, indicating that production of TNF alpha is just one of the mechanisms by which normal hemopoiesis is inhibited in AML LTMC, and that other factors are involved in this process. In keeping with this idea, we found very high levels of prostaglandin E, a hemopoietic inhibitor, in the supernatant of cultures that contained the soluble inhibitory activity. Interestingly, rhCSF-1 showed opposite effects on TNF production in normal (up-regulation) and AML (down-regulation) LTMC, which suggests the presence of functionally abnormal, leukemia-derived macrophages in AML LTMC. PMID- 1434798 TI - Effects of interferon-alpha (IFN) on the expression of interleukin 1-beta (IL-1), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF) in acute myeloid leukemia (AML) blasts. AB - Interferon-alpha (IFN) induces the enzyme 2-5 oligoadenylate synthetase (2-5 AS) in cells from patients with hairy cell leukemia and B-cell chronic lymphocytic leukemia and this is associated with a breakdown of certain species of cytokine messenger (m)RNA via the activation of a latent ribonuclease. We have studied the expression of the cytokines interleukin 1-beta (IL-1), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumour necrosis factor alpha (TNF) as well as of the ribonuclease activator 2-5 AS in the presence and absence of IFN in acute myeloid leukaemia (AML) blast cells from 26 patients. Before monocyte and T-cell depletion there was no expression of IL-1, IL-6 or GM-CSF, and only three of 13 patients studied expressed TNF mRNA. After cell depletion one or more cytokine was expressed in 31-62% of the 26 patients. Expression of one or more mRNA for IL-1, IL-6, GM-CSF and TNF after 18 h incubation was detected in 16 of 26 patients (63%) and this was particularly so in French-American-British (FAB) subtypes M4 and M5. Eight of nine patients with IL-6 mRNA expression and seven of 10 with IL-1 mRNA expression were in the FAB subtypes M4 and M5. Twenty-two of 26 patients showed induction of 2-5 AS mRNA in response to IFN in vitro. Exposure to IFN resulted in reduction of IL-1 mRNA in nine of 12 cases, of IL-6 mRNA in eight of nine, and GM-CSF mRNA in five of seven cases. TNF mRNA was unaffected by IFN despite 2-5 AS induction in 12 of 13 patients expressing this cytokine. In the presence of exogenous IFN, cells from six of seven patients studied showed inhibition of 3H-thymidine incorporation into DNA. DNA synthesis could also be abrogated in six of seven patients with anti-IL-1 monoclonal antibodies (MoAb) and in two of seven with anti-IL-6 MoAb. This inhibitory effect could be reversed in all patients when anti-IL-1 or anti IL-6 was given in combination with their corresponding cytokine. These data suggest that IFN may exert a therapeutic effect in a proportion of AML patients by blocking IL-1 and IL-6 mediated growth, consequent on activation of the ribonuclease activator 2-5 AS. PMID- 1434799 TI - L4415: further characterization of the rat model for human acute lymphocytic leukemia. AB - The biological properties of a transplantable lymphocytic leukemia, L4415 in the WAG/Rij rat, are described. The radiation-induced L4415 leukemia is characterized as a relatively slowly growing, non-immunogenic, immature T-cell leukemia which shows a reproducible growth pattern upon intravenous (i.v.) transfer. Survival time following i.v. inoculation is inversely related to the number of leukemic cells in the inoculum, which allows a quantitative estimate in terms of log leukemic cell kill of the effect of treatment. The first signs of leukemic growth are found in the bone marrow, the spleen, and the liver. Leukemic cells can be detected in the peripheral blood 13 days after inoculation. Due to replacement of normal hemopoietic tissue by leukemic cells and their number increasing exponentially thereafter, normal hemopoiesis is inhibited in the later stages of the disease as indicated by severe thrombocytopenia and anemia. Death is caused by a combination of splenic rupture, gastrointestinal and pulmonary hemorrhage, and impaired functions of heavily infiltrated organs. Hepatosplenomegaly and lymphadenopathy are prominent features at autopsy. Cyclophosphamide- and radiosensitivity of the clonogenic leukemic cells have been determined, a 2.9 log cell kill could be induced by single dose cyclophosphamide inoculation and a dosage giving a surviving fraction of 0.37 (D0) of 0.99 Gy with an extrapolation number (N) of 8.5 were calculated. Based on these data, the L4415 rat leukemia may be regarded as a relevant model for human acute lymphocytic leukemia and may thus serve to explore new treatment strategies. PMID- 1434800 TI - Interferon treatment for hairy cell leukemia: an update on a cohort of 69 patients treated from 1983-1986. AB - This report documents the follow-up information on 69 hairy cell leukemia (HCL) patients treated with interferon alpha-2b (IFN) as primary treatment from 1983 86. Follow-up through October 1991 shows only 11 patients have died. Forty-one of the 57 patients completing the intended 12 or more months of initial IFN treatment were eventually considered IFN failures. Thirty-nine required retreatment (38 received a second course of IFN and one received pentostatin). Two patients died without further therapy for HCL. The median time to interferon failure was 33 months. Sixteen patients are alive and have not required further treatment after completing their initial 12 or more months of interferon. Eight patients underwent a third course of interferon therapy at a median time after completion of a second course of IFN of 1.3 years. Seven patients developed a second malignancy; three of these patients developed a high-grade lymphoma between 3.5 and 6.5 years after initiation of interferon therapy. We conclude that although interferon provides excellent palliation, most patients will eventually require further treatment with interferon or chemotherapy. Future trials in HCL must be aware of second malignancies as a common cause of death. PMID- 1434801 TI - Phase I study of recombinant human interferon gamma in children with relapsed acute leukemia. AB - Fourteen children (ages 2-15 years) with acute leukemia in relapse were treated with daily recombinant interferon gamma for 14 days by subcutaneous injections at fixed dose levels of 0.1, 0.25, 0.5, or 0.75 mg/m2 (1.0, 2.5, 5.0, or 7.5 x 10(6) units/m2) without intrapatient escalation. Patients received a second 14-day course of therapy followed by thrice weekly administration unless there were signs of progressive disease or grade 3 or 4 toxicity. Side effects in the 13 evaluable patients included fever (n = 10), fatigue (9), decreased Karnofsky performance score (8), hypertriglyceridemia (8), myalgia (5), weight loss > 5% (4), elevated liver transaminases (4), and abdominal pain (3). There was only one grade 4 toxicity: one of the six patients at the 0.5 mg/m2 dose level developed reversible acute renal failure. One patient died of gastrointestinal hemorrhage due to disease-related refractory thrombocytopenia. One child had an oncolytic response and two others stable disease for 138 and 148 days. An appropriate dose level for phase II studies in children is 0.5 mg/m2 per day. PMID- 1434802 TI - Homoharringtonine is safe and effective for patients with acute myelogenous leukemia. AB - Homoharringtonine (HHT) is a cephalotaxine alkaloid with reported efficacy in acute myelogenous leukemia (AML). In a phase II trial, we evaluated HHT 5 mg/m2 by continuous infusion daily for 9 days in patients with relapsed or refractory acute leukemia and blastic phase of chronic myelogenous leukemia (BLCML). Sixty six patients were entered. There were 40 males and 26 females with a median age of 41 years (range 15-81). Of 43 patients with relapsed AML, seven achieved a complete remission (16%, 95% confidence interval 5%-27%). Although 11 patients with AML primarily resistant to an anthracycline/cytarabine combination did not respond, two of three patients primarily resistant to low-dose cytarabine achieved complete remission. No patients with acute lymphoblastic leukemia, biphenotypic leukemia, or BLCML responded. Hypotension during the administration of HHT was the most difficult toxicity encountered, requiring multiple interruptions of therapy in several patients and the administration of intravenous saline. Fluid retention and weight gain occurred in 29% of patients. Transient asymptomatic hyperglycemia was observed in 63% of patients. Other toxicity was mild and included nausea and vomiting, diarrhea, mucositis, hepatic dysfunction, and cardiac arrhythmias. As expected, severe myelosuppression occurred in all patients. HHT is well tolerated, but with unique problems associated with administration. It has demonstrable efficacy in pre-treated patients with AML, but its role in the treatment of this disease remains to be defined. PMID- 1434803 TI - Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia. AB - Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in patients with acute myelogenous leukemia (AML). In a phase I trial we evaluated cytarabine 100 mg/m2 by continuous infusion daily for 7 days in combination with four dose levels of HHT ranging from 1.5-5 mg/m2 by continuous infusion daily for 7 days to see if an effective regimen could be developed. Twenty-two patients with relapsed and/or primary refractory AML were treated. Seventeen males and five females were treated, with a median age of 40 years (range 19-63). There were five remissions in 14 patients with relapsed AML and none of eight responders in patients with primary refractory AML. None of the three patients treated at 1.5 mg/m2 dose level of HHT responded. Of three patients treated at the 3 mg/m2 dose level, there was one complete remission. At both 4 mg/m2 and 5 mg/m2, two of eight patients achieved complete remission. Four of the five remissions occurred in patients with acute promyelocytic leukemia. Drug induced pancytopenia was universal, and hypotension and fluid retention were more common at the higher dose levels. Other toxicity was mild and included nausea, vomiting, diarrhea, and mucositis. No significant hepatic, renal, or cardiac toxicity was seen. We conclude that the dose of HHT 4 mg/m2 for 7 days by continuous infusion in combination with cytarabine is safe for patients with AML; and this combination is appropriate for a phase II evaluation. PMID- 1434804 TI - High-dose cytosine arabinoside remission induction for acute myelogenous leukemia: comparison of two regimens of remission maintenance. AB - We report a single institution sequential trial of two maintenance treatment regimens for patients with acute myelogenous leukemia (AML). A total of 175 consecutive patients with AML received initial remission induction therapy with high-dose cytosine arabinoside (ara-C) and glucocorticoids. For the initial 63 patients (group A), the control population, planned maintenance treatment was with conventional-dose ara-C given over 4 days for up to 18 months. The subsequent 107 patients (group B) had planned maintenance therapy of up to 6 courses of daunorubicin, ara-C and prednisone and daily cis-retinoic acid for up to two years. The presenting features of group A and B patients were similar as were the response to remission induction, 60 and 52%, respectively. Severe neurological toxicity was encountered once after high-dose ara-C; no drug-related deaths occurred during maintenance treatment. Median duration of remission for group B patients was 9.9 months compared with 5.5 for group A (p = 0.0685). Median survival duration for the two groups was similar, 9.1 months for group A and 10.4 for group B. Survival of patients in group B who attained a complete remission was significantly better than that of patients in group A (p = 0.0439). The studies confirm our initial experience with remission induction using single agent high-dose ara-C and suggest a positive role for maintenance therapy in AML. PMID- 1434805 TI - Effect of high-dose methotrexate on plasma hypoxanthine and uridine levels in patients with acute leukemia or non-Hodgkin lymphoma in childhood. AB - We investigated the effect of high dose methotrexate (HDMTX) therapy on plasma hypoxanthine (Hx) and uridine (UR) concentrations in 12 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The initial plasma Hx level before the first administration of HDMTX (1 g/m2) was significantly higher in patients (25.5 +/- 17.5 microM) than that in healthy adult controls (4.0 +/- 1.4 microM). By 48 or 72 hours after the beginning of MTX infusion, the Hx concentration had decreased to 7.9 +/- 7.7 microM and 4.7 +/- 4.1 microM, respectively. This decrease of plasma Hx concentration after MTX infusion was also observed with the second course of HDMTX (3 g/m2) therapy. On the other hand, the plasma UR level did not change significantly. The in vitro treatment with 2 microM MTX of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficient mutant cells selected from HL-60 lowered the excretion of Hx into the culture medium. These data suggest a possible new explanation of the synergism of HDMTX and 6-thiopurines, for example 6-mercaptopurine and 6-thioguanine, since plasma Hx is considered to counteract 6-thiopurine toxicity through competition at the level of HGPRT. PMID- 1434806 TI - Third complementarity determining region (CDR III) sequence analysis in childhood B-lineage acute lymphoblastic leukaemia: implications for the design of oligonucleotide probes for use in monitoring minimal residual disease. AB - The genetic sequence of the third complementarity determining region (CDR III) of the immunoglobulin heavy chain (IgH) gene was analysed in 55 rearranged alleles from 36 children presenting with B-lineage acute lymphoblastic leukaemia (ALL). This confirmed the unique nature of these rearrangements. However, contrary to the hypothesis that the CDR III is produced by a random process of rearrangement, biased utilisation of diversity (D) segments and of joining (J) regions 4, 5 and 6 was demonstrated. Moreover, preferred sequence boundaries were seen in J regions 1 to 5 and were suggested at the 3'-end of certain D regions, notably D21/9 and DK1. Similar patterns of rearrangement have been noted in normal B lymphocyte clones. Together with relatively limited N nucleotide addition, these factors may restrict the potential sequence variability at the D-N-J junction. The occurrence of clonal progression by secondary gene rearrangements, such as V V replacement, favours the use of this site when designing clone-specific oligonucleotide probes for use in monitoring minimal residual disease (MRD). In cases where biased features of D-J rearrangement are shared by both the leukaemic and normal B-lymphocyte clones this could reduce the sensitivity of these probes in detecting low levels of residual disease. PMID- 1434807 TI - Mosaicism of trisomy 12 in chronic lymphocytic leukemia detected by non radioactive in situ hybridization. AB - Cytogenetic analysis using banding techniques of B-chronic lymphocytic leukemia (CLL) is hampered by the difficult in vitro proliferation of these tumor cells. For detection of specific cytogenetic aberrations these problems can be overcome with non-radioactive in situ hybridization (ISH). ISH may especially be applied for the detection of trisomy 12, which is the most frequent cytogenetic aberration in CLL. Sixty-seven patients with CLL, four normal controls and one lymphoblastoid B-cell line with a trisomy 12 were studied using a chromosome 12 specific probe. To determine the hybridization properties of the CLL cells, all samples were also hybridized with probes specific for chromosomes 1 and 8. All leukemias were analyzed by immunocytochemistry to determine the proportion of tumor cells. Eight cases (11%) showed a trisomy 12. After correction for the number of tumor cells, it was demonstrated that in almost all cases (7 out of 8), the aberration was present in a proportion of the tumor cells (between 30 and 72%). Except for one patient this mosaicism persisted with long-term follow-up. We conclude that the in vivo incidence of trisomy 12 in CLL is approximately 11%, and that trisomy 12 occurs in most instances in only a subpopulation of the leukemic cells. Both findings suggest that trisomy 12 in CLL is a late event. PMID- 1434808 TI - Relapse as acute monoblastic leukemia (AML-M5) of t(6;9) acute myeloblastic leukemia (AML-M2). AB - Two patients with acute myeloblastic leukemia with t(6;9)(p23;q34) translocation and classified as AML-M2 relapsed as acute monocytic leukemia (AML-M5). Trisomy 8 was found associated with t(6;9) at that time in both patients. Such changes in differentiation of leukemic cells have not previously been reported in this subtype of AML and add data favoring the pluripotent nature of the stem cell involved in leukemia with t(6;9). PMID- 1434809 TI - Polymerase chain reaction detection of residual disease in chronic myeloid leukemia patients in complete cytogenetic remission under interferon with or without chemotherapy. PMID- 1434810 TI - Autologous bone marrow transplantation for intensification of first remission in adult patients with acute lymphoblastic leukemia. PMID- 1434811 TI - Autologous bone marrow transplantation for acute myeloid and lymphoid leukemia. PMID- 1434813 TI - Are autotransplants effective in leukemia? PMID- 1434812 TI - Autologous graft-versus-host disease. PMID- 1434814 TI - Therapy of chronic myelogenous leukemia with related or unrelated donor bone marrow transplantation. PMID- 1434815 TI - Autografting in chronic myeloid leukemia with cultured marrow. PMID- 1434816 TI - Pathology and immunology of acute leukemia. AB - Tremendous advances in our understanding of acute leukemia have been made through the development of new technologies and close collaboration between immunologists, molecular biologists, and clinical oncologists. These technological advances have included the development of monoclonal antibodies (MoAb) reactive with surface antigens on leukemic cells which can help confirm the lineage and diagnosis of acute leukemia. More importantly, MoAb in conjunction with morphology and cytochemical stains have led to the identification of FAB-MO and the more common recognition of FAB-M7. MoAbs have also helped define prognostic groups, e.g., T-cell leukemia, mature B-cell leukemia, and rare groups such as CD7+ AML. However, the greatest advances in our understanding of acute leukemia has occurred with the application of genetic techniques. Disregulation of genes responsible for normal growth and differentiation initiates the molecular events that lead to the transformation and proliferation of cells recognized clinically as leukemia. Non-random cytogenetic abnormalities apparently contribute to this gene disregulation and specific abnormalities are associated with clinically important subgroups. In acute lymphoblastic leukemia (ALL), the t(9;22), t(1;19), and t(4;11) appear to have a poor prognosis. In acute myeloblastic leukemia (AML), -7/7q-;-5/5q-, 11q23 abnormalities have poor outcomes while t(15;17) and in some series t(9;11), t(8;21), and inv(16) have a good response to therapy. Molecular studies of somatic cell (immunoglobulin and T-cell receptor) gene rearrangements have assisted in the diagnosis and classification of ALL. The application of the polymerase chain reaction technique to specific gene rearrangements has provided a useful approach to minimal residual disease. Specific gene activation (N-myc, evi-1) or fusion genes such as the alpha retinoic acid receptor (alpha RAR) and pml have been identified as the specific cause of some cases of leukemia. The cloning of specific chromosomal breakpoints identified in leukemia (as has been done for CML) will result in specific probes which can be used to make the diagnosis rapidly at the molecular level. Because of the tremendous number of recent developments, this paper will focus only on major developments that will soon have a clinical impact. PMID- 1434817 TI - Newer aspects of prognosis in chronic lymphocytic leukemia. PMID- 1434818 TI - Autoimmunity and auto-immune syndromes associated with and preceding the development of lymphoproliferative disorders. AB - In this report the association of autoimmunity and autoimmune syndromes with lymphoproliferative disorders (LPD) is described in 15 patients. Non-Hodgkin's lymphoma (NHL) developed in 10 patients, Hodgkin's disease (HD) in 3 and chronic lymphocytic leukemia (CLL) in two. In most instances clinical and laboratory phenomena preceded the development/diagnosis of these disorders. Manifestations ranged from the presence of autoantibodies in the serum to the presence of both ill defined or incomplete autoimmune syndromes including cold urticaria, Raynaud's phenomenon, cold agglutinin disease, thyroiditis, nephrotic syndrome and vasculitis to typical systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and even one of scleroderma. It is suggested that in some patients (in)complete clinical manifestations of autoimmunity may precede the development of lymphoid neoplasias. The link between autoimmunity and lymphoproliferative disorders is briefly discussed. PMID- 1434819 TI - Secondary leukemia and myelodysplastic syndrome after treatment for Hodgkin's disease. PMID- 1434820 TI - Cytogenetics and oncogenes. AB - There is abundant evidence that leukemia arise through somatically acquired genetic changes. Familial or congenital predisposition is rarely involved. These genetic changes are often visible as chromosomal aberrations. Molecular analyses of the DNA sequences rearranged in leukemia has demonstrated the presence of cellular oncogenes which are modified (fused, mutated, truncated) by the specific translocations. This results in a disturbance of the delicate balance between proliferation and differentiation and constitute a major step towards cell transformation. Some of these genetic rearrangements have been analyzed in depth, but the exact defect that causes leukemia is often not yet understood. Meanwhile these studies have increased our knowledge of normal cell proliferation and differentiation and provided us with new tools for diagnosis and for developing more specifically targeted treatment. An example would be the production of antibodies that recognize specifically the new chimeric proteins. Oncogenesis is a complex and multiple step process that proceeds by acquisition of successive genetic insults. The different steps do not necessarily occurs following a predetermined order, although some secondary changes are preferentially induced by a given first mutation. In leukemia, sequential changes in karyotype are well documented but molecular makers for tumor progression have not yet been systematically investigated. This is one of our many challenges for the future. PMID- 1434821 TI - What can we learn from Bone Marrow Donors Worldwide (BMDW). PMID- 1434822 TI - Unrelated bone marrow donor transplantation (UD-BMT): interim results of the IMUST study. International Unrelated Search and Transplant. PMID- 1434823 TI - Immunotherapy of minimal residual disease in conjunction with autologous and allogeneic bone marrow transplantation (BMT). AB - Recent investigations in animal models of human lymphoid and myeloid leukemia suggest that induction of immune-mediated antitumor effects is feasible at the stage of minimal residual disease (MRD) using allogeneic immunocompetent lymphocytes following initial reconstitution with T cell depletion and/or activation of reconstituting syngeneic or allogeneic immune cells by recombinant interleukin-2 (rIL2). Pilot clinical trials in patients with leukemias and lymphomas at high risk to relapse following autologous bone marrow transplantation (BMT) suggest that beneficial antitumor effects may be achieved at the stage of MRD by home immunotherapy as soon as hematopoietic reconstitution occurs using rIL2 (Cetus) and alpha interferon (Roferon A) (Hoffmann LaRoche). Although results obtained from our open trial seem encouraging, prospective randomized trials and longer observation periods are needed in order to confirm immune-mediated antitumor effects in conjunction with autologous BMT in patients with malignant hematological disorders at high risk to relapse. Likewise, it seems that amplification of anti-leukemia effects following allogeneic BMT is feasible by post-transplant infusion of donor's peripheral blood lymphocytes for prevention and/or treatment of relapse. PMID- 1434824 TI - Selective metaphasic arrest of erythroblasts by vincristine in patients receiving high doses of recombinant human erythropoietin for myelosuppressive anemia. AB - As an introduction to a Satellite Symposium on the utilization of recombinant human erythropoietin (rHu-EPO) in hematology (Leukemia & Lymphoma 1992; 7 (Suppl.2): 94-100) a contribution to its mechanism of action was presented, and is published here. In three patients with advanced Hodgkin's disease treated with combination chemotherapy (MOPP) incorporating vincristine, and receiving at the same time a fixed daily dose of 8000 U of rHu-EPO subcutaneously for 10 to 15 days because of myelosuppressive anemia, myeloaspirates were performed one week before and 24 hours after the administration of vincristine. A dramatic accumulation of arrested metaphases in all stages of erythroblasts was found, while there was no augmentation of granulocytic metaphases. This is a further confirmation, following a previous contribution (Marmont AM: Haematol 1991; 76, 251-255), of the demonstration in man of the combined effects of erythropoietin as an erythroid mitogen and vincristine as a mitotic blocker. PMID- 1434825 TI - Diagnostic approach to the myelodysplastic syndromes. PMID- 1434826 TI - Therapy-related myelodysplastic syndromes and acute leukemias. PMID- 1434827 TI - Lymphocytic leukemias: new insights into biology and therapy. PMID- 1434828 TI - Epidemiology and etiology of acute leukemia: an update. PMID- 1434829 TI - Expression of adhesion molecules in lymphoproliferative disorders. AB - We review the role of adhesion molecule expression on malignant lymphoid cells as delineated by experimental studies and clinical observation. Adhesion molecules of the Ig superfamily, integrins, selectins, and the lymphocyte homing receptor CD44 mediate cell-to-cell and cell-to-extracellular matrix interactions. These molecules have been investigated with the aim (i) of defining certain biological features of the malignant cells, (ii) of providing a rationale to understand tumor organization, metastasis and organ specificity, and (iii) of detecting disease subsets and prognostic groups. PMID- 1434830 TI - Cellular and molecular studies on the early stages of human hematopoietic differentiation in culture of pure progenitors. AB - Methodology has been developed that enables virtually complete purification and recovery of early hematopoietic progenitors from human adult blood, a minority of which is multipotent and endowed with self-renewal capacities, i.e., exhibits stem cell properties. This report briefly reviews: (i) the key steps involved in the progenitor purification and assay procedure; (ii) the characterization of "pure" progenitors at the level of membrane antigen pattern and response to HGFs; (iii) the development of a liquid suspension culture for the pure progenitors, which allows synchronized and selective erythroid or GM differentiation, and hence may be utilized for the analysis of molecular mechanisms underlying early and late stages of hematopoiesis; (iv) the study of the expression and modulation of HGFRs expressed on progenitors. PMID- 1434831 TI - Approaches for an explanation of the differentiating effect of all trans retinoic acid in acute promyelocytic leukemia. PMID- 1434832 TI - Prognostic factors in acute lymphoblastic leukemia. PMID- 1434833 TI - Acute lymphoblastic leukemia: present and future. PMID- 1434834 TI - Role of bone marrow transplant in acute lymphocytic leukemia. PMID- 1434835 TI - Chemotherapy versus allogeneic or autologous bone marrow transplantation in second complete remission of acute lymphoblastic leukemia. PMID- 1434836 TI - Diagnosis of leukemia: morphology. PMID- 1434837 TI - Prognostic factors for selecting curative therapy for adult acute myeloid leukemia. PMID- 1434838 TI - Combined effect of very early intensification and prolonged post-remission chemotherapy in patients with AML. AB - The study combines the effects of prolonged postremission chemotherapy with that of very early intensification. 900 adult patients at all ages with newly diagnosed AML uniformly received TAD for induction and consolidation followed by monthly myelosuppressive maintenance for 3 years. In patients of 60+ years with persistent bone marrow blasts a second TAD course was given. In all patients of less than 60 years a second induction course started on day 21 even in aplasia with no blasts. Second induction was randomly either TAD or HAM. In the younger age group 69% attained CR and similar in the two arms the CR rate after 5 years is 35%. Including the 50% patients attaining CR in the higher age group the CR rate after 5 years is 32%. In 40 patients receiving allogeneic BMT and 21 patients receiving autologous BMT in first CR relapse free survival is similar to that from chemotherapy alone in a matched pair analysis. We conclude that age adapted very early intensification followed by prolonged postremission chemotherapy represents a therapeutic progress. PMID- 1434839 TI - High-dose cytosine arabinoside for the treatment of acute myeloid leukemia. Studies of the North American Marrow Transplant Group. PMID- 1434840 TI - Post-remission therapy in adults with acute myelogenous leukemia: the Eastern Cooperative Oncology Group (ECOG) experience. PMID- 1434841 TI - Allogeneic versus autologous marrow transplantation for patients with acute myeloid leukemia in first marrow remission. An update of the Genoa experience with 159 patients. PMID- 1434842 TI - Leukemic cell kill in autologous bone marrow transplantation: in vivo or in vitro? AB - Both the contribution of high dose chemo-radiotherapy ("conditioning treatment") prior to autologous bone marrow transplantation (ABMT) and "purging" of autologous marrow grafts to the prevention of leukemia relapse are being addressed in the present communication. Based on both preclinical and clinical studies, it is concluded that cures achieved after ABMT are mainly due to effective eradication of residual leukemic cells in the host. The chance that leukemia will relapse is due to leukemic cells reinfused with the graft is estimated to be less than 10%. PMID- 1434843 TI - High dose etoposide melphalan, total body irradiation and ABMT for acute myeloid leukemia in first remission. PMID- 1434845 TI - Autologous bone marrow transplantation in 2502 patients with acute leukemia in Europe: a retrospective study. PMID- 1434844 TI - Has IL2 a role in the management of minimal residual disease for acute leukemia? AB - Based on pre-clinical findings and on more recent preliminary in vivo data it has been suggested that immunotherapy with Interleukin 2 (IL2) may be employed in the treatment of acute leukemia patients. Here we shall discuss the biological and clinical observations which indicate that this innovative therapeutic approach may play a role in the management of minimal residual disease. PMID- 1434846 TI - Medical mythology: Hera (Juno). PMID- 1434847 TI - Expanded use of thrombolytic therapy. PMID- 1434848 TI - Medullary thyroid carcinoma--an uncommon cause of thyroid nodules but an important cause of thyroid neoplasms. PMID- 1434849 TI - The mast cell and idiopathic pulmonary fibrosis. PMID- 1434850 TI - Prolactin and carcinoma of the breast. PMID- 1434851 TI - The 25th anniversary of the Alfred Building at Saint Marys Hospital. PMID- 1434852 TI - Tissue plasminogen activator for treatment of livedoid vasculitis. AB - Livedoid vasculitis, a hyalinizing vasculopathy, is characterized by extensive formation of microthrombi and deposition of fibrin in the middermal vessels, which result in epidermal infarction, ulceration, and formation of stellate scars. In a prospective study of nonhealing ulcers in patients with livedoid vasculitis, we found a high incidence of anticardiolipin antibodies, lupus anticoagulants, increased levels of plasminogen activator inhibitor, and low levels of endogenous tissue plasminogen activator (t-PA) activity. This procoagulant tendency and decreased fibrinolysis may provide an explanation for the occlusive vasculopathy often noted in biopsy specimens from these patients. On the basis of these findings, we proposed that fibrinolysis with recombinant t PA would lyse microvascular thrombi, restore circulation, and promote wound healing. In six patients who had nonhealing ulcers caused by livedoid vasculitis and in whom numerous conventional therapies had failed, low-dose t-PA (10 mg) was administered intravenously during a 4-hour period daily for 14 days. Five of the six patients had dramatic improvement; almost complete healing of the ulcers occurred during hospitalization, and tissue oxygenation, as measured by transcutaneous oximetry, increased. The one treatment failure was due to rethrombosis of the microvasculature; this patient was subsequently re-treated but with concurrent anticoagulation, and her leg ulcers healed. We conclude that daily administration of a low dose of t-PA is safe and effective treatment for nonhealing ulcers due to occlusive vasculopathy. PMID- 1434853 TI - Medullary thyroid carcinoma: clinicopathologic features and long-term follow-up of 65 patients treated during 1946 through 1970. AB - We retrospectively reviewed the medical records of 65 consecutive patients with medullary thyroid carcinoma, who had had their primary surgical treatment at the Mayo Clinic during the years 1946 through 1970. Of these patients, 58 had sporadic and 7 had familial medullary thyroid carcinoma. Thyroid nodules were the most common initial manifestation. Near-total thyroidectomy was the most frequent initial operation. Survival was affected by the following factors: male sex, familial inheritance, size of the tumor, stage of the tumor (American Joint Committee on Cancer), and completeness of initial resection of the tumor. The mean duration of follow-up was 23.5 years, and the maximal follow-up was 36 years. Among 52 patients without initial distant metastatic involvement and with complete resection of the tumor, 20-year survival free of distant metastatic lesions was 81%. Overall 10- and 20-year survival rates were 63% and 44%, respectively. Because of the substantial morbidity and mortality associated with medullary thyroid carcinoma, early diagnosis and thorough initial resection of the tumor are important. PMID- 1434854 TI - Immunofluorescent staining for mast cells in idiopathic pulmonary fibrosis: quantification and evidence for extracellular release of mast cell tryptase. AB - In many diseases, retrospective analysis for determining the presence of mast cells has been difficult because of their loss of metachromatic staining properties once tissue has undergone formalin fixation. We quantified mast cells in peribronchiolar tissue of idiopathic pulmonary fibrosis (IPF) and in normal human lung by using rabbit antiserum to human mast cell tryptase. In lung biopsy specimens from 15 patients with IPF, the mean number of mast cells per high-power field in connective tissue directly adjacent to the lumen of small airways (0.5 to 2 mm in diameter) and other fibrotic foci was 29.9 +/- 10.8 in comparison with 13.7 +/- 3.5 in 16 normal controls (P < 0.001). In addition, mast cells in cases of IPF had an altered appearance--irregularity of the plasma membrane and release of extracellular tryptase. We conclude that the number of mast cells is increased in IPF and that the altered appearance of the mast cells suggests that they are activated and undergoing degranulation. PMID- 1434855 TI - The pituitary gland in patients with breast carcinoma: a histologic and immunocytochemical study of 125 cases. AB - Pituitary glands obtained at autopsy of 125 women with disseminated breast carcinoma were studied to determine whether pituitary prolactin cell abnormalities (hyperplasia or adenoma) might be involved in the pathogenesis of breast carcinoma. In addition, we studied 85 pituitary glands obtained from unselected, consecutive autopsies in women without breast carcinoma but who died of other diseases (control group). The frequency of lactotroph hyperplasia was slightly higher in patients with breast carcinoma than in the control group, but the difference was not statistically significant, nor were differences in the frequency and size of pituitary adenomas, prolactin-producing or otherwise. No correlation was found between the presence of lactotroph hyperplasia or prolactin producing adenomas (or both) and such factors as the patient's age, bilaterality of the carcinoma, previous treatment with tamoxifen citrate or oophorectomy, stage of disease, or survival. The frequency of breast carcinoma metastatic to the pituitary gland was higher in the study group than in the control group; however, the difference was not statistically significant. No preferential site of metastatic involvement in the pituitary gland was noted. Relative proportions of other lesions such as infarcts, cysts, lymphocytic infiltrates, and basophilic invasion were similar in the study and control groups. This study indicates that accumulation of prolactin cells, whether hyperplastic or adenomatous, cannot be considered a major risk factor for the genesis or progression of breast carcinoma. PMID- 1434856 TI - Pathology of surgically excised primary cardiac tumors. AB - Between 1957 and March 1991, 106 patients with 110 neoplasms that originated in the heart were treated surgically at the Mayo Clinic and had pathologic material available for review. The study group consisted of 39 male and 67 female patients, who ranged in age from 2 to 80 years. Benign atrial myxomas (64 in the left atrium and 16 in the right atrium) were the most commonly encountered neoplasm. The other benign tumors were nine fibromas, five lipomatous tumors, seven valvular fibroelastic papillomas, and one cardiac hamartoma (so-called oncocytic cardiomyopathy). In addition, eight patients had a primary cardiac malignant lesion: angiosarcoma, leiomyosarcoma, and malignant fibrous histiocytoma in two patients each and sarcoma (not otherwise specified) and osteogenic sarcoma in one patient each. The angiosarcomas originated in the right atrium, and the other malignant tumors originated in the left atrium. The histologic feature that most frequently predicted an adverse clinical outcome was the presence of mitotic figures, although highly cellular tumors and those with necrosis also tended to have a malignant course. PMID- 1434857 TI - Humoral hypercalcemia associated with a dysgerminoma. AB - A 16-year-old girl sought medical attention at the Mayo Clinic because of a 4.5 kg weight loss, hypercalcemia, and a pelvic mass. Preoperatively, the level of the beta-subunit of human chorionic gonadotropin was 147 IU/liter. After a brief period for observation and hydration, abdominal exploration revealed a stage III dysgerminoma; total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Within the dysgerminoma, syncytial giant cells expressed human chorionic gonadotropin-positive immunostaining in the cytoplasm. Postoperatively, the value of the beta-subunit of human chorionic gonadotropin decreased rapidly. The patient received whole-abdomen irradiation 4 weeks postoperatively, after which the level of calcium returned to normal. The patient has been free of disease for more than 7 years. PMID- 1434858 TI - Cutaneous micrographic surgery: Mohs procedure. AB - Skin cancer is an increasingly serious public health issue that affects a high percentage of the population. Surgical resection is still standard treatment for skin cancer, but for difficult cases, cutaneous micrographic surgery, originally described by Mohs, is our preferred technique because of the routine methodic accuracy for evaluation of the surgical margin, the high rate of oncologic cure, and the tissue-sparing quality of the procedure. We report the Mayo Clinic experience with cutaneous micrographic surgery from July 29, 1986, through June 30, 1991, which consisted of 3,355 cases (principally basal cell and squamous cell carcinoma). Herein we discuss practical concerns about this procedure: duration of the technique, reconstruction, cure rates, tumors best treated by cutaneous micrographic surgery, and cost. In addition, we review the Mayo Clinic multidisciplinary management of difficult skin cancers. PMID- 1434859 TI - Cyclosporine treatment of inflammatory bowel disease. AB - Numerous uncontrolled studies and one controlled trial of cyclosporine therapy suggest that this selective inhibitor of cell-mediated immunity may be of benefit in patients with chronically active Crohn's disease. In addition, uncontrolled studies indicate that cyclosporine may be useful in the following settings: fistulous Crohn's disease; corticosteroid sparing in Crohn's disease; severe ulcerative colitis; and refractory proctosigmoiditis. The major advantages of cyclosporine therapy are apparent efficacy in patients with refractory disease and a rapid onset of response. Nevertheless, the incidence of relapse is high after cyclosporine therapy is discontinued, and this outcome is not prevented by low-dose maintenance therapy. Furthermore, the frequency of occurrence of cyclosporine-related side effects during treatment of patients with inflammatory bowel disease is high; paresthesias and hypertrichosis are the two most common adverse effects reported in the literature. Although the potential for permanent renal damage is of concern, serious, irreversible toxicity seldom occurs. Ongoing clinical trials will provide additional information about the efficacy and safety of cyclosporine for the aforementioned indications. PMID- 1434860 TI - Gestational diabetes mellitus: now is the time for detection and treatment. AB - The extent of universal screening for gestational diabetes and the incidence of gestational diabetes mellitus (GDM) by diagnosis were analyzed in four primary care sites. The medical records of 798 women were reviewed to identify the presence of historical risk factors, familial determinants, and biophysical attributes associated with GDM and to determine whether screening and diagnostic tests consistent with national criteria had been completed, as well as to obtain the method of delivery and the weight and overall medical status of the infants. Of the 798 women, less than 60% underwent screening. Overall, 1.5% of the women were diagnosed with GDM, seven of whom were identified through screening. Eighty nine infants were classified as large for gestational age, 61 of whom weighed more than 4,000 g. Of these 61 infants with macrosomia, 61% were born to women who either were not screened or had negative screening results. Most of these women had risk factors consistent with GDM. The likelihood that a substantial proportion of these women would have delivered normal-sized infants had they undergone proper screening, diagnosis, and treatment prompted us to conclude that universal screening for GDM should be adopted. PMID- 1434861 TI - World War II and Mayo. PMID- 1434862 TI - Mitral valve operation in postinfarction rupture of a papillary muscle: immediate results and long-term follow-up of 22 patients. AB - The long-term clinical outcome was assessed in 22 patients (15 men and 7 women; mean age, 68 years) who underwent mitral valve replacement or repair for acute mitral regurgitation due to postinfarction rupture of a papillary muscle during the period 1981 through 1990 at the Mayo Clinic. All but three patients underwent operation within the first 3 weeks after acute myocardial infarction. The perioperative mortality was 27%, and the estimated actuarial survival rate at 7 years postoperatively was 47% and 64% for the entire group and for the patients who survived the operation, respectively. The concomitant performance of a coronary artery bypass grafting procedure was the only factor identified that improved both immediate and long-term survival. Patients with a decreased preoperative left ventricular ejection fraction (less than 45%) had somewhat greater short-term and long-term mortality than did those with a left ventricular ejection fraction of 45% or more, but the difference was only of borderline statistical significance. Other factors such as age, sex, severity of coronary artery disease, preoperative existence of congestive heart failure, and timing of the operation in relationship to occurrence of the infarction had no effect on survival. Of the 13 long-term survivors, 10 had significant clinical improvement in comparison with their preoperative state. PMID- 1434863 TI - A prospective randomized comparison of epidural infusion of fentanyl and intravenous administration of morphine by patient-controlled analgesia after radical retropubic prostatectomy. AB - In a prospective, randomized study, continuous infusion of epidural fentanyl citrate (group E) was compared with patient-controlled intravenously administered morphine sulfate (group P) for analgesia in 66 men after radical retropubic prostatectomy. Although both methods provided satisfactory analgesia, the mean comfort level scores were lower (that is, greater comfort) in group E than in group P at all observation times. The difference in mean resting comfort level scores between groups E and P was statistically significant (P < or = 0.05) at 9 of the 11 observation times. In addition, significant differences in comfort level scores were noted at 8 of the 11 observation times during deep breathing, 5 of 11 during coughing, and 3 of 9 during ambulation. Maximal and minimal comfort level scores recorded by each patient during the course of the study were significantly lower (that is, less pain) in group E than in group P for all four categories of activity. The percentage of patients who reported no pain was significantly higher in group E than in group P at 9 of 11 observation times during resting and 5 of 11 observation times during deep breathing. No significant differences were noted in side effect profiles or duration of hospital stay. In summary, when two effective methods of analgesia used after radical retropubic prostatectomy were compared prospectively, patients who received epidural infusion of fentanyl were more comfortable than those with patient-controlled intravenous administration of morphine, as evidenced by lower mean, maximal, and minimal comfort level scores and a greater proportion of patients with complete relief of pain. PMID- 1434864 TI - Predictors of outcome after percutaneous endoscopic gastrostomy: a community based study. AB - Percutaneous endoscopic gastrostomy (PEG) is used to provide nutrition for patients who are unable to eat but have a functionally intact gut. Clinical guidelines for PEG are uncertain and have been derived mainly from referral practices. We performed a population-based cohort study in 97 residents of Olmsted County, Minnesota, referred for PEG between January 1982 and December 1988 to determine complications, duration of tube feeding, and survival. Follow up continued until death or February 1990. Inpatient and outpatient records were reviewed to determine indications, comorbid conditions, level of consciousness, and limitations in activities of daily living. Outcomes determined after referral for PEG included type and number of complications, tube removal, and survival. Statistical methods used included Kaplan-Meier and proportional hazards regression analyses. PEG placement was successful in 94% of patients. Although complications occurred in 70% of patients, they usually were minor (88%) and most occurred within 3 months. In 24 patients, tubes were removed because eating was resumed. The probability of surviving 30 days, 1.5 years, and 4 years after referral for PEG was 78%, 35%, and 27%, respectively. The major causes of death within and after 30 days were pneumonia, heart disease, and vascular disease of the central nervous system. An increased risk of death after referral for PEG placement was associated with older age, male gender, diabetes, and specific indications for PEG. If validated in other population-based studies, these predictors of survival after referral for PEG placement could be used to identify patients with a low probability of survival who may not benefit from PEG. PMID- 1434865 TI - Importance of breast biopsy incision in final outcome of breast reconstruction. AB - Currently, breast cancer is one of the most common malignant lesions among women in North America--it occurs in one in every nine such women. Approximately 180,000 cases will be diagnosed this year. During the past 3 years at the Mayo Clinic, approximately 4,000 breast biopsies were performed. In approximately 20% of such biopsy specimens, a malignant lesion will be identified. Surgeons should be aware of the current possibilities in breast reconstruction and should consider the cosmetic result in the placement of breast biopsy incisions. Even lesions in the superior or inferior portions of the breast are accessible through generous periareolar incisions. The biopsy incision should be within the confines of a possible skin excision for mastectomy to avoid creating two scars if the specimen proves cancerous. The choice of site for the biopsy incision, however, should never jeopardize the treatment of the cancer. Appropriate preoperative planning will ensure optimal cosmetic and therapeutic results in the management of breast lesions. PMID- 1434866 TI - Cemented versus noncemented total hip arthroplasty--embolism, hemodynamics, and intrapulmonary shunting. AB - Bone cement implantation syndrome is characterized by hypotension, hypoxemia, cardiac arrhythmias, cardiac arrest, or any combination of these complications. It may result from venous embolization that occurs in conjunction with intramedullary hypertension in the femur during insertion of the prosthesis in patients undergoing cemented total hip arthroplasty (THA). Intramedullary hypertension does not occur in patients undergoing noncemented THA. In this study, we sought to compare embolization between patients undergoing cemented and noncemented THA and to determine whether this state resulted in cardiorespiratory deterioration. In this prospective investigation of 35 patients undergoing elective THA, we used transesophageal echocardiography and invasive hemodynamic monitoring, and in 12 of them, we monitored distribution of pulmonary ventilation and perfusion intraoperatively. Embolization was significantly greater after insertion of the prosthesis in patients undergoing cemented than in those undergoing noncemented THA. Cemented THA was also associated with decreased cardiac output and increased pulmonary artery pressure and pulmonary vascular resistance. Increases in ventilation-perfusion mismatching, however, could not be demonstrated 30 minutes after insertion of the femoral prosthesis. Intraoperative monitoring for embolism may help physicians assess patients in whom cardiorespiratory function deteriorates during THA. PMID- 1434867 TI - Allergic reactions to latex among health-care workers. AB - With the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic and the practice of protecting health-care workers from all body fluids, the use of rubber gloves has increased, as has occupational allergy to latex among health care workers. During 1991, 49 Mayo Medical Center employees sought assessment and treatment of rhinitis, conjunctivitis, contact urticaria, contact dermatitis, asthma, or eczema thought to be related to exposure to latex. Most of these persons had a history of atopy and worked in areas where rubber gloves were used and changed frequently. Of the 49 subjects, 34 had positive results of skin tests to latex products, and the sera from 19 of 35 persons tested contained increased latex-specific IgE antibodies. Employees with sensitivity to latex (and co workers in the immediate areas) should use vinyl gloves and should notify their own health-care providers of their sensitization. Changes in job assignment may be necessary for some persons. PMID- 1434868 TI - Wladyslaw Bieganski--father of modern Polish medicine. PMID- 1434869 TI - Use of the internal mammary artery for myocardial revascularization in a patient with radiation-induced coronary artery disease. AB - A 9-year-old boy with clinical stage IIA Hodgkin's disease underwent radiotherapy to the neck and mediastinum. Twenty-two years later, he sought medical attention because of angina pectoris. Cardiac catheterization revealed proximally located high-grade stenoses of the left main, left anterior descending, circumflex, and right coronary arteries. He underwent coronary artery bypass grafting with use of the left internal mammary artery to the left anterior descending coronary artery and reversed saphenous vein grafts to the circumflex and right coronary arteries. The postoperative course was uncomplicated. Previous radiotherapy to the mediastinum should be considered a risk factor for the development of premature coronary artery disease. Surgical revascularization is the preferred method of management. A combination of an internal mammary artery graft and a saphenous vein graft should be used in young patients. PMID- 1434870 TI - Pancreatic pseudocyst that compressed the inferior vena cava and resulted in edema of the lower extremities. AB - To our knowledge, edema of the lower extremities has not previously been reported as a sign of a pancreatic pseudocyst. In this case report, we describe a 66-year old man in whom such a lesion compressed the inferior vena cava and caused pronounced leg swelling. After drainage of the pseudocyst, the edema did not recur. Although the most well-known complications of pancreatic pseudocyst are pain, hemorrhage, rupture, infection, and obstruction of adjacent viscera, bilateral edema of the lower extremities can be the initial manifestation of this lesion. PMID- 1434871 TI - Dermatologic manifestations of human immunodeficiency virus infection. AB - Human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) have become major health problems in the United States, and patients with manifestations of these diseases are seen by physicians in all areas of medicine. Cutaneous manifestations develop in as many as 92% of HIV positive persons. Familiarity with these manifestations facilitates early diagnosis and enhances the care of HIV-infected patients. The spectrum of mucocutaneous disorders in these patients includes an acute exanthem, multiple infections, neoplastic processes, and miscellaneous disorders. Herein we review the most common and the most specific dermatologic manifestations associated with HIV infection, which often are atypical, more severe, or less responsive to treatment than the corresponding diseases encountered in non-HIV-infected persons. PMID- 1434872 TI - Surgical treatment of postinfarction rupture of a papillary muscle. PMID- 1434873 TI - The evolution of management of postoperative pain. PMID- 1434874 TI - To PEG or not to PEG--that is the costly question. PMID- 1434875 TI - Colonoscopy. PMID- 1434876 TI - 100th anniversary of Sister Mary Joseph Dempsey. PMID- 1434877 TI - Results of a randomized controlled trial of carotid endarterectomy for asymptomatic carotid stenosis. Mayo Asymptomatic Carotid Endarterectomy Study Group. AB - We undertook a randomized controlled trial designed to compare the effects of carotid endarterectomy with medical treatment using low-dose aspirin in patients with asymptomatic carotid stenosis. During 30 months of recruitment, 71 randomized and 87 eligible nonrandomized patients participated in a follow-up protocol. The total ipsilateral perioperative stroke and death rate was 0% among randomized patients and 3% among nonrandomized patients, and the major stroke and death rate was 0% for both groups. Too few cerebral ischemic events occurred to judge the comparative effectiveness of carotid endarterectomy versus low-dose aspirin for asymptomatic carotid stenosis. The trial was terminated early because of a significantly higher number of myocardial infarctions and transient cerebral ischemic events in the surgical group than in the medical group. Most of the events were not temporally related to the surgical procedure, but there was evidence that these events could have related to the absence of aspirin use in the surgical group. These observations reinforce the appropriateness of the use of aspirin throughout the perioperative period and beyond (unless contraindications exist) in patients with asymptomatic carotid stenosis who undergo carotid endarterectomy. PMID- 1434878 TI - Ischemic cholangitis in hepatic allografts. AB - In this report, our objectives are to introduce the term "ischemic cholangitis" as an etiologic designation and to describe its manifestations. Herein we use the label "ischemic cholangitis" as a collective term for ischemic bile duct necrosis, cholangitis caused by ischemia but without necrosis, and biliary fibrosis as a manifestation of ischemic damage. The condition was observed in 12 allografts, either at the time of retransplantation (9 cases) or at autopsy (3 cases). Ischemic cholangitis involved primarily perihilar extrahepatic and intrahepatic bile ducts. The findings included duct necroses (eight cases), strictures (four cases), and cholangiectases (four cases); some of these features coexisted. In addition, complicating ascending cholangitis and cholangitic abscesses were noted in three cases. Ischemic cholangitis was caused by hepatic artery thrombosis (in nine patients) or stenosis (in one) or by occlusion of parabiliary arteries by fibrointimal proliferations, probably attributable to old thromboses (in two, in conjunction with associated foam cell arteriopathy in one). Biopsy specimens before retransplantation or autopsy were obtained in 11 patients, only 1 of whom had an infarct as direct evidence of ischemia. Nine patients had evidence of biliary obstruction or bile flow impairment; in two cases, specimens were normal or nondiagnostic relative to cholangitis. Features of cellular rejection associated with the manifestations of bile flow impairment and ischemia were noted in five cases. Thus, biopsy features that suggest biliary obstruction, with or without cellular rejection, may be a manifestation of ischemic cholangitis. We conclude that ischemic cholangitis is an important cause of cholestatic graft failure but that this type of cholangitis is difficult to diagnose because of its misleading biopsy manifestations. PMID- 1434879 TI - Health risk behaviors and medical sequelae of childhood sexual abuse. AB - The relationship between childhood sexual abuse and subsequent health risk behaviors and medical problems was examined in 511 women who had used a family practice clinic in a rural midwestern community during a 2-year period (1988 and 1989). These women completed a questionnaire that assessed various health risk behaviors--smoking, drinking, drug abuse, number of sexual partners, and age at first intercourse--and a medical symptom checklist that assessed 38 medical problems related to major systems of body function, the somatization scale from the SCL-90, a screen for sexual abuse, and a brief measure of social support. The results indicated that sexually abused women, who represented 22.1% of the sample, reported significantly more medical problems, greater levels of somatization, and more health risk behaviors than did the nonabused women. More severe abuse (for example, penetration or multiple abusers) correlated with more severe problems. Extent of social support correlated inversely with the number of gynecologic problems reported in the sexually abused group. Fewer than 2% of the sexually abused women had discussed the abuse with a physician. To identify and assist victims of sexual abuse, physicians should become experienced with nonthreatening methods of eliciting such information when the medical history is obtained. PMID- 1434880 TI - Leiomyosarcoma of the stomach: determinants of long-term survival. AB - To determine factors associated with a favorable long-term prognosis in gastric leiomyosarcoma, we retrospectively reviewed the medical records of 93 Mayo Clinic patients with this biopsy-proven tumor diagnosed during the 25-year period from 1964 through 1988. Six patients who had Carney's triad (gastric epithelioid leiomyosarcoma, pulmonary chondroma, and functioning extra-adrenal paraganglioma) were excluded from data analysis. The other 87 patients participated in follow-up until death or for a median duration of 5.8 years for those who were alive at the conclusion of the study. The most common symptoms at the time of initial assessment were abdominal pain (51%), melena (36%), and weight loss (16%). Most often, the tumor was located in the greater curvature (25%), fundus (20%), or lesser curvature (16%) of the stomach. Two percent of patients had tumors at multiple sites. All 87 gastric leiomyosarcomas were histologically confirmed; 38% were grade 1, 37% were grade 2, and 25% were either grade 3 or grade 4. Metastatic involvement was noted in 15% of patients at the time of diagnosis. The 5- and 10-year survival rates were 45% and 34%, respectively, and the 5- and 10 year tumor recurrence rates were 57% and 65%, respectively. Variables that were associated with long-term survival were low histologic grade of the tumor, absence of metastatic lesions, and small tumor size (P < 0.01); variables such as site of the tumor, initial symptoms, age, and sex provided no significant additional prognostic information. PMID- 1434881 TI - Conditions associated with carpal tunnel syndrome. AB - With use of a comprehensive medical records-linkage system, we identified the comorbid conditions and risk factors in the residents of Rochester, Minnesota, who had a diagnosis of carpal tunnel syndrome during 1961 through 1980. In 43.2% of the 1,016 patients, no associated conditions were found on review of the medical records, whereas associated conditions were documented in 56.8%. The most frequent of these conditions were Colles' fracture, rheumatoid arthritis, hormonal agents or oophorectomy (or both), diabetes mellitus, and, among men, occupations that involved excessive use of the hands. Rheumatoid arthritis, diabetes mellitus, and pregnancy were significantly more frequent among the study patients with carpal tunnel syndrome than in the general population of Rochester, Minnesota. The standardized morbidity ratio was 3.6 for rheumatoid arthritis, 2.3 for diabetes mellitus, and 2.5 for pregnancy. The population attributable risk for pregnancy among women 15 to 44 years old was 7.0%. The standardized morbidity ratio for polymyalgia rheumatica was not significantly increased. PMID- 1434882 TI - Tibia vara in a patient with Bardet-Biedl syndrome. AB - The Bardet-Biedl syndrome is characterized by polydactyly, hypogonadism, obesity, mental retardation, and retinitis pigmentosa. Several other skeletal findings include hip dysplasia, short stature, and skull deformities. The patient described in this report has the classic findings of Bardet-Biedl syndrome in conjunction with tibia vara and irregular physes of the lower extremities. PMID- 1434883 TI - Isolated antral narrowing associated with gastrointestinal cryptosporidiosis in acquired immunodeficiency syndrome. AB - A 33-year-old man with human immunodeficiency virus infection had severe protracted diarrhea. Radiologic assessment disclosed narrowing of the gastric antrum. Biopsy specimens revealed diffuse Cryptosporidium infection of the antral mucosa. Isolated antral narrowing due to Cryptosporidium gastritis should be added to the list of gastrointestinal complications associated with acquired immunodeficiency syndrome (AIDS). PMID- 1434884 TI - Intubation of critically ill patients. AB - Respiratory failure is one of the most common causes for admission to an intensive-care unit. Any patient with loss of central nervous system control of breathing, neuromuscular respiratory failure, or impairment of gas exchange may require tracheal intubation and mechanical ventilation. Tracheal intubation provides a conduit for ventilatory support, maintains the patency of an airway that has potential for obstruction, protects the airway from the contents of the stomach, and allows access to the trachea for pulmonary hygiene. Although the mechanics of intubation are easily learned, many factors must be considered in critically ill patients. Herein we summarize the principles of tracheal intubation in acutely ill patients. PMID- 1434885 TI - Cardiac transplantation: surgical considerations and early postoperative management. AB - The limited availability of donor hearts is the major constraint to the expanded application of cardiac transplantation. As many as 25% of potential recipients will die before a donor becomes available. Since 1986, hospitals that receive Medicare and Medicaid funds have been required to ask family members of all brain dead patients who are potential donors whether they have considered organ donation. The United Network for Organ Sharing is responsible for the national organ procurement and transplantation network as well as the national organ transplantation scientific registry. The increasing occurrence of multiorgan donation is amplifying the demands for intensive-care management of donors. Donor and recipient are matched on the basis of ABO blood group and body size. The donor operation can be performed in any standard operating room. Although the maximal acceptable ischemic time for a donor heart is 4 to 6 hours, briefer preservation times result in better hemodynamic performance after transplantation and a significantly lower 30-day mortality. The technique of choice in most medical centers is orthotopic cardiac transplantation. Postoperatively, most patients remain in the intensive-care unit for 1 or 2 days and in the hospital for 1 to 2 weeks. Standard intensive-care procedures after transplantation, including nursing and cardiovascular management as well as the treatment of failure of the donor heart, are reviewed. A comprehensive educational program for patients and their families should optimize the outcome after heart transplantation. The overall charges for heart transplantation averaged $114,000 in 1987, 80% of which were hospital charges.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434886 TI - Techniques of immunosuppression after cardiac transplantation. AB - Modulation of the normal immune response is the major challenge for successful organ transplantation. Cardiac allograft rejection is primarily the result of activation of T cells. Most currently used immunosuppressive agents mainly affect the T-cell-mediated limb of the immune system. Immunosuppressive strategies can be considered to have three goals: (1) prophylaxis against rejection early after cardiac transplantation, (2) long-term maintenance prophylaxis, and (3) treatment of acute rejection. The extent of immunosuppression needed varies with the time after transplantation and the rejection profile of the individual patient. The goal is to provide sufficient immunosuppression to retard rejection without causing undesirable side effects, including infection and neoplasms. PMID- 1434887 TI - Wilder Penfield--contributor to the surgical treatment of epilepsy. PMID- 1434888 TI - Carotid endarterectomy: a little more light at the end of the tunnel. PMID- 1434889 TI - Ischemic cholangitis. PMID- 1434890 TI - Medical symptoms, health risk, and history of childhood sexual abuse. PMID- 1434891 TI - Barium enema study. PMID- 1434892 TI - National survey of use of mesna for the prevention of cyclophosphamide-induced hemorrhagic cystitis in recipients of bone marrow transplants. PMID- 1434893 TI - Dr. Arpad Gerster and the Mayo brothers. PMID- 1434894 TI - Pitfalls of "bench surgery" and autotransplantation for renal cell carcinoma. AB - Under certain circumstances, extracorporeal surgical treatment ("bench surgery") followed by autotransplantation is indicated for renal cell carcinoma. During a 10-year period, 20 patients (16 men and 4 women) underwent bench surgery and attempted autotransplantation for renal cell carcinoma at our institution. The autotransplantation was successful in 16 patients but unsuccessful in 4 because of postoperative renal vascular thrombosis or extensive tumor involvement, which resulted in inadequate renal vein for anastomosis. Of the 16 patients who underwent successful autotransplantations, 4 (25%) subsequently had locally recurrent renal cell carcinoma (a mean of 35 months after initial autotransplantation). Only 6 of the 16 patients who underwent successful autotransplantation were ultimately free of both carcinoma and dialysis. Although an ex vivo surgical procedure can be beneficial for certain patients with renal cell carcinoma, computed tomographic scanning of the autotransplantation site should be performed every 3 to 6 months postoperatively for early detection of local tumor recurrence. PMID- 1434895 TI - Early-stage squamous cell carcinoma of the glottic larynx managed with radiation therapy. AB - Between January 1975 and December 1985, 45 patients with carcinoma in situ or invasive squamous cell carcinoma of the glottic larynx received radiation therapy at the Mayo Clinic. Local control in the entire group of 45 patients was 84% (in 6 of 6 with carcinoma in situ and in 32 of 39 with invasive cancers). Three of seven patients (43%) with local recurrences underwent successful larynx preserving surgical procedures; thus, the rate of laryngeal preservation was 91%. In our study of several treatment factors, including the duration of treatment, type of treatment (continuous course versus split course), photon energy (60Co versus 4-MV photons versus 6-MV photons), total dose, and dose per fraction, we found that only total dose of 6,300 cGy or more was associated with significantly improved local control (in 35 of 38 patients [92%]). Two patients (4%) died of uncontrolled delayed nodal metastases, one of which was preceded by a local recurrence. Severe laryngeal edema developed in two patients, associated with recurrent glottic carcinoma in one of them. No larynx was lost because of complications. In our current treatment recommendations, patients receive a total dose of 6,300 cGy in 28 fractions of 225 cGy each, administered in a continuous course with use of 6-MV photons. PMID- 1434896 TI - Clinical performance of parathyroid hormone immunometric assays. AB - Three immunometric assays of parathyroid hormone (PTH)--a commercial immunoradiometric assay, an in-house immunoradiometric assay, and an immunochemiluminometric assay--were evaluated in 50 patients with surgically proven primary hyperparathyroidism. Of these patients, 43 had increased values with the commercial assay (sensitivity, 86%), whereas 45 patients had increased concentrations with both the in-house immunoradiometric and the in-house immunochemiluminometric assays (sensitivities, 90%). Because of the results of this comparison study, we confidently chose the immunochemiluminometric assay as our routine assay; this assay was evaluated retrospectively in 361 patients with surgically proven primary hyperparathyroidism. In 45 patients, PTH values were below the upper limit of normal (sensitivity, 88%). The results indicate that the sensitivities of current immunometric assays are approximately 90%. Twenty patients who had hypercalcemia associated with malignant involvement were assessed with the immunochemiluminometric assay. Of these 20 patients, 19 had subnormal PTH values, and 1 had a value within the normal range. In contrast, in the past, PTH values determined with radioimmunoassays have often been in the normal range for such patients. Thus, an immunometric PTH assay is superior to a radioimmunoassay in the differential diagnosis of hypercalcemia associated with malignant disease. PMID- 1434897 TI - Dirofilaria immitis: a rare, increasing cause of pulmonary nodules. AB - Dirofilariasis is an unusual but increasing cause of solitary pulmonary nodules. In this study, we reviewed the entire experience with dirofilariasis at our institution. Five such patients were identified. In all patients, the Dirofilaria immitis infection manifested as a solitary pulmonary nodule, and all patients underwent thoracotomy for diagnosis. None required systemic treatment. D. immitis is found in dog, cat, wolf, coyote, and fox populations throughout the United States, but the highest concentrations have been noted in the eastern, southeastern, and southern coastal states. The distribution of human cases of D. immitis infection has a similar pattern. Pulmonary dirofilariasis should be included in the differential diagnosis of peripheral noncalcified pulmonary nodules, especially in endemic areas. PMID- 1434898 TI - Medical mythology: Achilles. PMID- 1434899 TI - Weight change and serum lipoproteins in recipients of renal allografts. AB - Hyperlipoproteinemia is common in recipients of renal allografts. In this study, serum lipids and some possible contributing factors--weight gain, weight relative to ideal body weight, daily dose of prednisone, serum creatinine, 24-hour urinary protein, and diabetes mellitus--were assessed in 100 patients. At the end of the first year after transplantation, 57 of the 100 patients had total serum cholesterol concentrations of 240 mg/dl or more--40 of 75 patients without diabetes and 17 of 25 with diabetes. The mean values for weight gain (11.2 kg) and actual weight relative to ideal body weight (19.4 kg) were significantly greater (P = 0.029 and P = 0.01, respectively) in the subgroup of patients without diabetes who had total serum cholesterol values of 240 mg/dl or more at 1 year after transplantation than in those with values of less than 240 mg/dl. The daily dose of prednisone and the serum creatinine levels were similar in these two subgroups. The 24-hour urinary protein measurements were greater at 1 month than at 1 year in both patients with and those without diabetes. Perhaps the initial dietary advice for patients who have undergone renal transplantation should emphasize control of total caloric intake; subsequently, intake of cholesterol and fat can be modified in those patients who have persistent hyperlipoproteinemia. PMID- 1434900 TI - Fluorescent in situ hybridization: use of whole chromosome paint probes to identify unbalanced chromosome translocations. AB - By identifying structural chromosome anomalies, the clinical cytogenetics laboratory can play a critical role in the diagnosis and treatment of patients with birth defects. Although many new staining techniques have been developed throughout the years to aid in the detection of anomalous chromosomes, some abnormalities still pose a special challenge to cytogeneticists. This difficulty is especially evident in patients with an abnormal chromosome that does not produce a recognizable banding pattern by conventional staining techniques. We describe a recently discovered method of identifying chromosomes by using whole chromosome-specific DNA probes and fluorescent in situ hybridization and provide examples of how this new procedure facilitated the identification of chromosome abnormalities in two patients with multiple birth defects. PMID- 1434901 TI - Fistulous pseudoaneurysm complicating surgical accessory pathway interruption for Wolff-Parkinson-White syndrome. AB - Pseudoaneurysms of the left ventricle are unusual operative complications that have commonly been associated with replacement of the mitral valve. In this report, we describe a 31-year-old man who was referred to our institution because of atypical chest pain. He had previously undergone three operations for ablation of an accessory pathway because of Wolff-Parkinson-White syndrome. A pseudoaneurysm of the left ventricle was noted on transesophageal echocardiography, biplanar left ventriculography, and ultrafast cine computed tomography of the heart. Elective surgical repair was successful. Although rare, this case demonstrates an unusual but potentially serious complication of surgical treatment of Wolff-Parkinson-White syndrome. PMID- 1434902 TI - Occult cardiac tamponade detected by transesophageal echocardiography. AB - Transesophageal echocardiography is a safe, minimally invasive procedure that should be considered when the diagnosis of cardiac tamponade is a possibility and when conventional methods fail to provide conclusive diagnostic information. In this report, we describe a 74-year-old man in the intensive-care unit whose condition was unstable postoperatively because of an occult loculated pericardial effusion and cardiac tamponade. Routine noninvasive and invasive monitoring, including hemodynamic monitoring and transthoracic echocardiography, failed to confirm definitively the suspected diagnosis of cardiac tamponade. In addition, because of the hemodynamic instability of the patient, transporting him for definitive tests (such as fast computed tomographic scanning of the mediastinum, which could not be performed at the bedside) for assessment of cardiac tamponade was relatively contraindicated. In our patient, the diagnostic information obtained by transesophageal echocardiography may have been lifesaving. PMID- 1434903 TI - Efficacy and safety of total parenteral nutrition in pediatric patients. AB - Pediatric patients differ from adult patients because of active musculoskeletal growth and development of visceral organs and because they have a proportionately smaller nutritional reserve, especially premature infants. Measures of outcome of effective nutritional support in pediatric patients who have experienced trauma or medical disease or who have undergone surgical procedures include weight gain, increased height and circumference of the head, increased hepatic synthesis of plasma proteins, immunocompetence, decreased morbidity, improved survival, and fast recovery. If a pediatric patient cannot eat or be tube-fed enterally after 3 days of recovery and support with fluids, parenteral nutrition is indicated. Examples in which this treatment has dramatically decreased morbidity include gastroschisis, short-bowel syndrome, necrotizing enterocolitis, and Hirschsprung's disease. Contraindications to its use include severe congenital (usually genetic) defects and terminal cancer, conditions in which life expectancy and quality of life are severely decreased. The team approach to parenteral and enteral nutrition in pediatric patients is preferred, and stable patients receiving long-term nutritional support, including infants, should be considered for home parenteral nutrition. When administered by protocol, parenteral nutrition is safe in pediatric patients. In properly selected pediatric patients, direct and indirect costs for such therapy may be significantly less than those in adults, and the cost-to-benefit ratio is appreciably higher when life expectancy, parental pleasure, and potential work productivity are considered. Ethical and social issues in initiating and discontinuing parenteral nutrition are best decided during thorough empathic discussions between physicians and parents. PMID- 1434904 TI - Strategies for prevention of infection after cardiac transplantation. AB - Infection remains a major cause of morbidity and mortality after cardiac transplantation. Most infections occur during the first few months after transplantation. Although late infection does occur, the risk of infection during maintenance immunosuppression is low in the absence of recurrent rejection that necessitates augmentation of suppression of the immune response. Before cardiac transplantation, the risk factors for infectious disease in potential candidates should be assessed. A detailed history of past infections should be elicited, and patients should be screened for the presence of active indolent infection. In addition, potential donors must be thoroughly assessed for organ-transmittable infection. Many common infections that may occur after cardiac transplantation can be prevented with the use of appropriate prophylactic regimens directed toward cytomegalovirus, Toxoplasma gondii, Pneumocystis carinii, and herpes simplex virus. Periodic surveillance serologic tests and cultures after cardiac transplantation facilitate early diagnosis and prompt institution of appropriate therapy. PMID- 1434905 TI - Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection). AB - Pathologic examination of both the recipient and the donor heart is critical to the success of cardiac transplantation. Idiopathic dilated cardiomyopathy and end stage ischemic heart disease are still the most common diagnoses for which cardiac transplantation is performed in the United States. After transplantation, the donor heart is susceptible to immunologic (acute and chronic rejection), infectious, and ischemic injury. Other long-term changes, such as hypertrophy of the myocytes and interstitial fibrosis, may also affect the function of the transplanted heart. Periodic endomyocardial biopsies are important for monitoring the status of the transplanted heart. In patients treated with cyclosporine, the clinical signs of rejection may be minimal, and routine biopsy is the only means of detecting early rejection. PMID- 1434906 TI - "Bench surgery" for renal cell carcinoma: a proper niche. PMID- 1434907 TI - Management of T1 and T2 squamous cell carcinoma of the glottic larynx. PMID- 1434908 TI - High-altitude baking at Mayo. PMID- 1434909 TI - Increased plasma concentrations of endothelin in congestive heart failure in humans. AB - Congestive heart failure is characterized by decreased cardiac output and increased peripheral vascular resistance. Endothelin, a peptide found in plasma, is a potent vasoconstrictor. We hypothesized that plasma concentrations of endothelin are increased in humans with congestive heart failure. Plasma samples were obtained from 71 healthy control subjects and 56 patients with congestive heart failure. The mean plasma concentration of endothelin, measured by radioimmunoassay, was 7.1 +/- 0.1 pg/ml in the 71 normal control subjects but 12.6 +/- 0.6 pg/ml in the 56 patients with heart failure (P = 0.001). To evaluate the relationship between circulating endothelin and clinical stage of congestive heart failure, we categorized patients into two groups--those with mild heart failure (New York Heart Association class I or II) and those with severe heart failure (class III or IV). Circulating endothelin in the 24 patients with mild disease was 11.1 +/- 0.7 pg/ml, significantly higher than in normal subjects (P < 0.001). Endothelin in the 32 patients with severe heart failure was 13.8 +/- 0.9 pg/ml, a level significantly higher than that in the group with mild disease (P = 0.029). In the 56 patients with congestive heart failure, a negative correlation was found between plasma concentration of endothelin and left ventricular ejection fraction (r = -0.279; P = 0.037). These data demonstrate that the plasma concentration of endothelin is increased in humans with congestive heart failure and that the level correlates with the severity of disease. Endothelin may have a role in the increased vascular resistance in patients with chronic congestive heart failure. PMID- 1434910 TI - Colonic tone and motility in patients with irritable bowel syndrome. AB - In this study, our aim was to test the hypothesis that colonic tone is abnormal in patients with irritable bowel syndrome (IBS). We studied eight patients with IBS and eight age-matched asymptomatic control subjects, in whom tone and motility were measured by an electronic barostat and by pneumohydraulic perfusion manometry, respectively. Tone and motility were recorded from the descending colon for a 14-hour period--3 hours awake, 7 hours asleep, 2 hours fasting after awakening, and 2 hours postprandially. In patients with IBS and in healthy subjects, colonic tone decreased by up to 50% during sleep and increased promptly on awakening. Fasting colonic tone (as quantified by the volume in the barostat balloon) in the awake state was not significantly higher in patients with IBS than it was in healthy subjects (125 +/- 13 versus 152 +/- 15 ml; P = 0.19). Tone increased postprandially in both study groups, and the increase was greater in healthy subjects than it was in patients with IBS (P < 0.05). The motility index during fasting was greater in patients with IBS than it was in healthy control subjects (3.2 +/- 0.6 versus 1.6 +/- 0.4; P = 0.05), and the postprandial increase in motility index was greater in the healthy subjects. Preprandially and postprandially, we noted a trend for high-amplitude prolonged contractions to be more frequent in patients with IBS than in healthy subjects. We conclude that colonic tone in patients with IBS showed the same nocturnal and postprandial variations as it did in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434911 TI - Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-predominant irritable bowel syndrome: a pilot study. AB - Serotoninergic innervation may contribute to the control of colonic motility and to visceral sensation from the large bowel. Indeed, ondansetron hydrochloride, a selective 5-hydroxytryptamine type 3 receptor antagonist, has been shown to slow colonic transit in healthy volunteers. Thus, we wished to determine whether 5 hydroxytryptamine type 3 receptor blockade slows colonic and small bowel transit in patients with diarrhea-predominant irritable bowel syndrome (IBS) and whether symptoms would be ameliorated with drug therapy. Of 14 patients with well established IBS who entered a randomized, double-blind, placebo-controlled crossover pilot trial of 4 weeks of treatment with ondansetron, 16 mg three times daily, 11 completed the study. A minimal "washout period" of 4 weeks (median, 7 weeks) separated the two phases of the trial because patients were required to have similar symptoms before both periods of the study. Colonic transit tended to be longer during drug therapy than during the placebo trial, but this difference was not significant. Small intestinal transit and orocecal transit were unchanged by the drug. The integrated and peak postprandial increases in neurotensin, peptide YY, and human pancreatic polypeptide in serum were not significantly different in the drug and placebo periods. After treatment with ondansetron, stool consistency improved significantly; however, stool frequency, stool weight, abdominal pain, and the symptom criteria for IBS were not significantly altered by the drug. The results of this pilot study suggest that the motor effects expected with 5-hydroxytryptamine type 3 receptor blockade (namely, slowed colonic transit) may be diminished in some patients with IBS. The subjective improvement in stool consistency may reflect changes in the perception of defecation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434912 TI - Magnetic resonance imaging of facial vascular anomalies. AB - In 36 patients, facial vascular anomalies were studied with 46 magnetic resonance (MR) examinations, 9 angiograms, and 5 computed tomographic scans. All lesions were categorized into classic pathologic groups on the basis of radiologic and pathologic studies, clinical examination, and behavior. Overall, 2 juvenile hemangiomas, 3 capillary malformations (port-wine stains), 18 venous malformations, 9 lymphatic malformations, and 4 arteriovenous malformations were found. MR imaging was superior to computed tomography and angiography for demonstrating the precise anatomic extent of the facial vascular anomalies and their relationship to the adjacent soft tissues but was inferior to computed tomography for demonstrating radiopaque structures such as trophic bone changes and phleboliths. MR imaging was also inferior to angiography in determining the nidus and the exact nature of collateral vascular structures in arteriovenous malformations. MR studies confirmed the clinically suspected diagnosis of facial vascular anomalies and demonstrated typical characteristics for each type of lesion. MR imaging is an ideal initial technique to triage patients with facial vascular anomalies for appropriate management, including observation, endovascular therapy, or surgical excision. PMID- 1434913 TI - Benign lymphocytic infiltrate of the skin: correlation of clinical and pathologic findings. AB - In a retrospective study of 137 biopsy specimens of skin from 137 patients (69 men and 68 women) that had been obtained between 1972 and 1989 at our institution and that had perivascular and periappendageal lymphocytic infiltrates characteristic of those described as benign lymphocytic infiltrate (BLI), we determined the specificity of the histologic diagnosis and the correlation with clinical data. The final diagnoses, based on clinical and laboratory data and histologic findings, were BLI (59), possible BLI (7), lupus erythematosus (LE) (12), possible LE (7), procainamide-induced LE (1), insect bites (9), possible insect bites (3), polymorphous light eruption (4), lymphocytoma (4), urticaria (4), and indeterminate or miscellaneous diagnoses (27). BLI is a clinical and histologic syndrome that can be heterogeneous in origin. We recommend careful evaluation to exclude other disorders such as LE, polymorphous light eruption, lymphocytoma, and insect bites. Direct immunofluorescence microscopy and immunophenotypic studies may help distinguish BLI from LE. PMID- 1434914 TI - Balance studies and polymeric glucose solution to optimize therapy after massive intestinal resection. AB - The aim of this study was to determine whether fluid homeostasis could be maintained by using a hypo-osmolar (200 to 221 mosmol/kg), relatively low-sodium (50 to 52 mmol/liter) solution that contained a glucose polymer in a 54-year-old patient with high ileostomy output attributed to short-gut syndrome and resultant prerenal azotemia. Sequential balance studies were performed to assess stool and urinary output, stool fat, and urinary electrolytes initially during intravenous rehydration and subsequently during administration of the necessary fluids and nutrients exclusively by oral supplementation. The additional effects of high-fat and low-fat diet, loperamide hydrochloride, and octreotide acetate were evaluated. When the patient sipped a hypo-osmolar oral rehydration solution while she was awake during the day and received a high dose of loperamide and a 40-g fat, disaccharide-free diet, salt and water homeostasis was maintained. The addition of octreotide did not substantially enhance fluid balance; rather, it increased fecal fat and fluid losses from the small bowel. Thus, hypo-osmolar polymeric glucose solutions maintain fluid homeostasis in patients with the short gut syndrome. In such patients, simple balance studies are useful for assessing the absorptive capacity of the residual intestine, for developing an optimal individualized treatment, and for eliminating the need for costly, long-term home parenteral nutrition. PMID- 1434915 TI - Spontaneous coronary arterial dissection and isolated eosinophilic coronary arteritis: sudden cardiac death in a patient with a limited variant of Churg Strauss syndrome. AB - Isolated eosinophilic coronary arteritis expressed as a limited variant of the Churg-Strauss syndrome (allergic granulomatosis and angiitis) is a rare condition. Equally as rare is the entity of isolated spontaneous coronary arterial dissection associated with eosinophilic arteritis. A 57-year-old woman with a history of asthma and recurrent hypersensitivity (anaphylactoid) reactions to various exogenous allergens was found dead in her home; no premonitory complaints had been noted during the preceding days. Autopsy revealed focal occlusion of the left anterior descending and first diagonal coronary arteries by discrete dissecting hematomas of the media as the cause of sudden and unexpected death. Histologically, the affected arterial wall showed eosinophilic inflammation characteristic of this limited expression of the Churg-Strauss syndrome. To our knowledge, sudden cardiac death caused by arterial dissection in isolated eosinophilic coronary arteritis has not previously been reported. PMID- 1434916 TI - Mayo Medical Center Brain Injury Outpatient Program: treatment procedures and early outcome data. AB - The rehabilitation of persons with brain injuries has proved challenging; community reintegration is often unsuccessful. Herein we describe our intensive group-oriented outpatient treatment program for persons with brain injury and report outcome data for the graduates of the program thus far. This interdisciplinary program emphasizes the development of cognitive skills, compensation techniques, social skills, emotional adjustment, leisure skills, physical fitness, and health maintenance. Although goals are individually determined, independent living and employment are goals for most participants in the program. Before initial participation, all candidates undergo an extensive 2 day assessment. Typically, a patient remains in the program for approximately 6 months. The specific group treatment approaches used in the program are discussed. Outcome data are assessed with use of the Portland Adaptability Inventory and goal attainment scaling, as well as comparisons of preprogram and postprogram employment status and level of independent living. Our initial results support the conclusion that this comprehensive and integrated treatment program is efficacious in rehabilitating persons with mild to moderate sequelae of brain injury. PMID- 1434917 TI - Management of patients after cardiac transplantation. AB - During the past decade, the morbidity and mortality associated with cardiac transplantation have decreased dramatically. The current survival for patients who undergo orthotopic cardiac transplantation is 80 to 90% at 1 year and 70 to 80% at 5 years; these results are attributed chiefly to improved immunosuppression and the consequent decrease in infectious illnesses and rejection. Because surgical mortality and technique have not changed appreciably during the past 20 years, improved survival can be ascribed to advances in the medical management of recipients of cardiac transplants. Medical problems frequently encountered in such patients include allograft rejection, allograft vasculopathy, hypertension, renal dysfunction, hyperlipidemia, hyperglycemia, malignant disorders, general surgical disease, and osteopenic bone disease. Hence, the expertise needed for management of patients who undergo cardiac transplantation is not confined to a particular specialty--optimal care necessitates the integrated efforts of a team, including transplant physicians and personnel to provide broad subspecialty and laboratory support. Meticulous management with proactive intervention and minimal effective immunosuppression will prevent or ameliorate many problems and contribute to increased survivorship and improved quality of life. For additional substantive improvement in long-term survival and quality of life for recipients of cardiac allografts, multicenter, prospective, and placebo-controlled clinical investigations will be necessary. PMID- 1434918 TI - Total lymphoid irradiation: a novel and successful therapy for resistant cardiac allograft rejection. AB - Total lymphoid irradiation (TLI) is a novel type of adjuvant immunosuppression for patients who undergo cardiac transplantation and have refractory allograft rejection during standard immunosuppressive therapy. TLI consists of 6 to 10 fractions of 80 cGy (1 cGy = 1 rad) of irradiation to lymphatic tissues with use of the standard mantle and inverted Y fields. We have used TLI in six patients with biopsy-proven rejection that was refractory to standard treatments, including cyclosporine, azathioprine, antilymphocyte antibodies, and corticosteroids. In five patients, recalcitrant rejection was resolved after completion of TLI, and resolution persisted during long-term follow-up (17 to 30 months; mean, 22.2 months). In each patient, a substantial increase in the CD8 (suppressor T-lymphocyte) subset and elimination of B lymphocytes were demonstrated, findings that also persisted. Side effects were mild and primarily limited to transient leukopenia. In four patients, a readily treated cytomegalovirus reactivation was noted during TLI; thus, a causal relationship was suggested. In recipients of cardiac allografts who have refractory rejection, TLI provides long-lasting amelioration of the rejection profile. This result may be attributable to a relative enhancement of the suppressor T-cell subset and elimination of the B-lymphocyte line. Side effects are minimal, but monitoring for cytomegalovirus activation or reactivation is recommended. PMID- 1434919 TI - A genetic review of complete and partial hydatidiform moles and nonmolar triploidy. AB - Complete and partial hydatidiform moles are genetically aberrant conceptuses. Usually, complete moles have 46 chromosomes (diploidy), all of paternal origin. Most partial moles have 69 chromosomes (triploidy), including 23 of maternal origin and 46 of paternal origin. Triploidy that involves 23 paternal chromosomes and 46 maternal chromosomes is not associated with molar placental changes and, rarely, can result in a live-born infant with multiple birth defects. Herein we review the mechanisms of fertilization that may produce these unbalanced sets of parental chromosomes and the role of genomic imprinting as a possible explanation for these clinical conditions. PMID- 1434920 TI - Medical mythology: Hermes (Mercury). PMID- 1434921 TI - A potential role for endothelin in congestive heart failure. PMID- 1434922 TI - Understanding irritable bowel syndrome and gastrointestinal motility. PMID- 1434923 TI - Facial vascular anomalies: clarity with magnetic resonance imaging and biologic classification. PMID- 1434924 TI - Dr. Charles H. Mayo and Mayowood. PMID- 1434925 TI - Inpatient treatment of severe nicotine dependence. AB - The most severely nicotine-dependent patients who have tried traditional treatment programs without success may require maximal intervention to achieve abstinence. In the Clinical Research Center at the Mayo Clinic, we assessed the feasibility of an inpatient treatment program for 24 such subjects, who were hospitalized (in groups of 6) for 2 consecutive weeks. A combination of behavioral, chemical-dependence, and transdermal nicotine-replacement therapy was provided in a smoke-free, protected milieu. Components of the program included group therapy, management of stress, exercise, daily lectures, and supervised activities. The mean age of the 18 women and 6 men was 51.3 years (range, 29 to 69 years). The mean duration of smoking was 33.7 years, and the number of cigarettes smoked per day at the time of admission averaged 33.2. The most frequent tobacco-related medical illnesses were chronic obstructive pulmonary disease, arteriosclerosis obliterans, and coronary artery disease. All subjects but two--each smoked part of a cigarette--remained abstinent from the use of cigarettes while in the Clinical Research Center, and all completed the 2-week inpatient program. The subjects underwent follow-up for 10 weeks after dismissal and were contacted periodically thereafter. At 1 year, 7 of the 24 subjects (29%) had maintained continuous abstinence from smoking, and their self-reported status at 1 year was verified biochemically. PMID- 1434926 TI - Coexpression of class I major histocompatibility antigen and viral RNA in central nervous system of mice infected with Theiler's virus: a model for multiple sclerosis. AB - Chronic infection of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in central nervous system (CNS) demyelination similar to multiple sclerosis. Demyelination induced by TMEV is mediated, in part, by class I-restricted CD8+ T lymphocytes. For these T cells to function, they must recognize virus-infected CNS targets in the presence of class I major histocompatibility complex (MHC) antigen. Therefore, we studied in vivo expression of class I MHC antigen and viral antigen-RNA in prototypic mouse strains that are susceptible (SJL/J) or resistant (C57BL/10SNJ) to TMEV-induced demyelination. In brains of resistant mice, viral antigen-RNA expression peaked on day 3 after infection and was effectively diminished by day 5 such that few virus-infected cells were ever detected in the spinal cord. In contrast, susceptible mice demonstrated delay in clearance of TMEV from the brain and a subsequent increase and persistence of viral antigen-RNA in the spinal cord for as long as 277 days. Viral infection resulted in "upregulation" of class I MHC expression in the CNS. Class I MHC antigens were expressed as early as 1 day after infection in the choroid plexus of both strains of mice before detection of viral antigen or inflammation. In resistant mice, class I MHC expression predominated in the gray matter of the brain and spinal cord on day 7 after infection but returned to undetectable levels by day 28. In susceptible mice, class I MHC expression in the CNS persisted and was intense in the white matter of the spinal cord throughout chronic infection and demyelination. No class I MHC expression was detected in the CNS of uninfected mice. Coexpression of viral RNA and class I MHC antigen was demonstrated in CNS cells by using simultaneous in situ hybridization and immunoperoxidase technique. These results support the hypothesis that a class I-restricted immune response directed against virus infected cells may be important in the mechanism of demyelination. PMID- 1434928 TI - Spontaneous rupture of the spleen due to infectious mononucleosis. AB - Spontaneous splenic rupture is an extremely rare but life-threatening complication of infectious mononucleosis in young adults. Although splenectomy remains effective treatment, reports of successful nonoperative management have challenged the time-honored approach of emergent laparotomy. On retrospective analysis of our institutional experience with 8,116 patients who had this disease during a 40-year period, we found 5 substantiated cases of atraumatic splenic rupture due to infectious mononucleosis. Four additional cases of suspected splenic rupture were noted. All nine patients were hospitalized and treated (seven underwent splenectomy and two were treated with supportive measures only), and they remain alive and well. In patients with infectious mononucleosis suspected of having rupture of the spleen, a rapid but thorough assessment and prompt implementation of appropriate management should minimize the associated morbidity and mortality. On the basis of review of the medical literature and careful scrutiny of our own experience, we advocate emergent splenectomy for spontaneous splenic rupture in patients with infectious mononucleosis. PMID- 1434927 TI - Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988. AB - To determine trends in the incidence of pancreatic cancer and associated survival, we conducted a population-based study in Olmsted County, Minnesota. From 1940 through 1988, 219 residents of Olmsted County (120 men and 99 women) were diagnosed as having exocrine pancreatic cancer. All patients were Caucasians, and 92% had a histologically confirmed diagnosis. The mean annual adjusted incidence of pancreatic cancer per 100,000 population was 8.5 overall (11.3 for men and 6.6 for women). During the course of the study, the incidence rates increased in women (P < 0.05) and in both genders combined (P = 0.06) but not in men (P = 0.4). The male:female ratio decreased from approximately 2:1 for 1940 through 1949 to 1.5:1 for 1980 through 1988. The incidence was significantly associated with increasing age (P < 0.001) and male gender (P < 0.001) but not calendar period (P = 0.19). The overall median duration of survival was 2.8 months. The 1-year survival rate was only 14%, and no patient lived for more than 55 months after pancreatic cancer was diagnosed. Men and women had similar survival rates. The increased incidence of pancreatic cancer among women may be due in part to the increasing life span of women and the increasing occurrence of pancreatic cancer in the aged. PMID- 1434929 TI - Henry Jordan--pioneer in physical training. PMID- 1434930 TI - Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high-density lipoprotein cholesterol. AB - In a retrospective analysis, 63 participants in a cardiac rehabilitation preventive cardiology program were identified as having low blood concentrations (mean, 34 mg/dl) of high-density lipoprotein cholesterol (HDL-C) and a mean total cholesterol level of 223 mg/dl after 3 months of hygienic measures (aerobic exercise, avoidance of tobacco, diet, and weight loss) designed to increase the HDL-C level. These patients (treatment group) were treated with low-dose, time release nicotinic acid (mean, 1,297 mg/day) for a mean duration of 7.4 months. All subjects were able to take the drug without intolerable side effects. Fifty four patients similar to those in the treatment group participated in the same program but were not treated with nicotinic acid (control group). Exercise, diet, body weight, and smoking remained stable throughout the period of observation. For the treatment group, HDL-C levels increased a mean of 18% (+6 mg/dl), total cholesterol concentrations decreased 9% (-20 mg/dl), the ratio of total cholesterol to HDL-C decreased 25% (from 6.8 to 5.1), low-density lipoprotein cholesterol levels decreased 13% (-20 mg/dl), and triglyceride levels decreased 20% (from 165 mg/dl to 132 mg/dl). Aspartate aminotransferase and uric acid concentrations were minimally increased after treatment, and the blood glucose level was unchanged. In the control group, HDL-C levels increased a mean of 8% (+3 mg/dl) and the other blood lipid variables were not improved after a mean of 8.3 additional months of diet and exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1434931 TI - Venous thromboembolism associated with hip and knee arthroplasty: current prophylactic practices and outcomes. AB - Joint registry and hospital data bases for 5,024 total hip and total knee arthroplasties done between 1986 and 1988 at the Mayo Clinic were used to study prophylactic measures and frequency of symptomatic deep venous thrombosis and pulmonary embolism. In virtually all patients, graduated compression stockings were used, with or without another type of prophylaxis. Only 44 of 3,115 patients who underwent hip arthroplasty (1.4%) and 32 of 1,909 patients who underwent knee arthroplasty (1.7%) had definite or probable deep venous thrombosis or pulmonary embolism. Death definitely or possibly attributable to pulmonary embolism occurred in 11 patients who underwent hip arthroplasty (0.35%) and 1 patient who underwent knee arthroplasty (0.05%). Although patients with a history of deep venous thrombosis or pulmonary embolism were more likely to receive warfarin than were patients without such a history, the relative risk of symptomatic deep venous thrombosis or pulmonary embolism in patients who underwent hip arthroplasty and received warfarin postoperatively was approximately half that in patients who received other types of prophylaxis. The risk of death from pulmonary embolism was similarly diminished in the group that received warfarin. The lower rates of these complications in the patients who received warfarin support the prophylactic use of this agent after total hip arthroplasty. PMID- 1434933 TI - Changes in the scope and responsibility of medicine. PMID- 1434932 TI - Reye's syndrome in Olmsted County, Minnesota: did it exist before 1963? AB - In this study, our goals were to determine whether Reye's syndrome existed before the first published report of this entity in 1963 and to describe the long-term incidence and trend of this syndrome. Medical and pathologic records and pathologic specimens for Mayo Clinic patients, including those who were residents of Olmsted County, Minnesota, were reviewed through the facilities of the Rochester Epidemiology Project. On review, 12 cases were identified for the period 1920 through 1962; 2 of these cases were in Olmsted County residents. Of the 12 cases identified before 1963, 10 were in patients younger than 5 years of age. In addition to the aforementioned two cases, five others in Olmsted County were diagnosed between 1963 and 1989. Incidence rates were computed for the Olmsted County population. The number of cases and rates per 100,000 persons younger than 18 years of age in that population were 2 cases (0.3) for 1920 through 1962, 4 cases (0.7) for 1963 through 1980, and 1 case (0.4) for 1981 through 1989. Although cases found during the earlier periods may have included disorders that mimic Reye's syndrome, the recommended criteria from the Centers for Disease Control were applied to review of medical records and supported by pathologic findings in the liver. The data showed an age distribution tending toward young patients and no seasonality of occurrence. The incidence rates in Olmsted County, Minnesota, showed an increase for 1963 through 1980 over previous decades, followed by a decrease. The small numbers preclude any conclusion about trends in the incidence rates. PMID- 1434934 TI - Detection of migratory silicone pseudotumor with use of magnetic resonance imaging. AB - A patient with silicone gel breast implants, who experienced capsular contracture of the left breast that was treated by closed capsulotomy, sought medical attention because of numbness and pain in the left medial forearm and hand. Inflammatory masses subsequently developed in the left anterior axillary and antecubital regions. Magnetic resonance imaging revealed silicone pseudotumors, and mammography confirmed implant rupture and gel extrusion along fascial planes into the axillary region. PMID- 1434935 TI - Optimizing nicotine-dependence treatment: a role for inpatient programs. PMID- 1434936 TI - Virus-induced demyelination: from animal models to human diseases. PMID- 1434937 TI - Pancreatic cancer in 1992: has any progress been noted? PMID- 1434938 TI - Spontaneous rupture of the spleen in patients with infectious mononucleosis. PMID- 1434939 TI - Problems associated with Medicare. PMID- 1434940 TI - Esophagopericardial fistulas. PMID- 1434941 TI - Effects of aging and food restriction on the trigeminal ganglion: a morphometric study. AB - A quantitative morphometric study of the rat trigeminal ganglion was conducted to determine the changes that occur with aging. All measurements were tracked from young to old age in two rat groups simultaneously. One group was fed ad libitum, the other was maintained on restricted food intake from 6 weeks on. Immunocytochemical and radioimmunoassay techniques were used to study the neuron group that produces the peptide, CGRP and to compare it with the CGRP-negative neuron group. We observed that in the trigeminal ganglion, soma diameters and nucleus diameters of all neurons, whether CGRP positive or negative, increased modestly with age; so did total ganglion weight. Food restriction delayed, but did not prevent the increases in neuron diameters. No significant changes occurred as a function of age in the total number of neurons per ganglion, the ratio of CGRP positive to CGRP negative neurons and ganglion content of CGRP. Food restriction did not affect the parameters that remained constant with age. These findings are in contrast to the marked inhibitory effect of food restriction on age-related increase in thyroid calcitonin, a hormone that is encoded by the same gene as CGRP. PMID- 1434942 TI - Age-related changes in concentrations of vasopressin in the central nervous system and plasma of the male Wistar rat. AB - The results of studies on the influence of age on concentrations of vasopressin (VP) in blood plasma and hypothalamic and extrahypothalamic brain sites have not been unequivocal. Studies on extrahypothalamic concentrations of VP in the aging rat have used two age groups only and have mainly provided semiquantitative data. For these reasons we determined, by radioimmunoassay, the concentrations of vasopressin in thirteen brain structures and in the plasma of 3-, 10-, 20- and 28 month-old male Wistar rats. Age-related decreases in VP concentrations were found in the pituitary gland, hypothalamus, thalamus, midbrain, medulla oblongata, amygdala and pineal gland, while an increase was noted in plasma. Decreases in the concentration of VP in the amygdala and pineal gland occurred between 3 and 10 months of age and probably represent developmental changes. In the pituitary, thalamus, midbrain, medulla oblongata and plasma, differences in the concentration of VP were also found between 10-month-old and older animals and are probably related to aging. The finding of increased plasma VP concentrations in aged animals agrees with the notion that neuronal function does not necessarily decline with age and suggests that neurons may even be activated. Age related changes in VP concentrations were not observed in the other structures examined. It has been reported that the VP innervation of a number of brain structures depends on testosterone. Despite reports to the contrary VP concentrations do not generally decline in these structures with aging. PMID- 1434943 TI - Dissociation kinetics of the uterine estrogen receptor-estradiol complex are unaltered in aging C57BL/6 mice. AB - Several, though not all, estrogen-dependent phenomena show reduced responsiveness to estradiol (E2) during aging. One factor contributing to this reduced sensitivity could be an increase in the dissociation rate of the estrogen receptor-hormone complex. We therefore studied the effect of aging on the dissociation rate of 3HE2 from the uterine cytosolic estrogen receptor (ER) of C57BL/6 mice that had been ovariectomized 48 h earlier. Measurements were made at 28 degrees C at two concentrations of cytosol. In dilute cytosol ([ER] = 0.01 nM) the dissociation of ER-3HE2 displayed a single phase, first order profile which did not differ among young (4-6 month), middle-aged (15-18 month) and old (23-30 month) mice. In more concentrated cytosol ([ER] = 2 or 6 nM) the dissociation of ER-3HE2 displayed a biphasic first order profile that consisted of an initial rapidly dissociating phase followed by a more slowly dissociating phase. There was no effect of age on the dissociation rate constant (K) of either the rapid (K 1) or slow (K-2) phase. Shortening the time allotted for the concentrated cytosol to equilibrate with 3HE2 before measuring the dissociation rate reduced the fraction of the receptor hormone complex that dissociated in the slow phase, but, once again, the dissociation profiles did not differ between age groups. These results indicate that uterine ER dissociation kinetics remain unaltered in middle aged and old mice and are therefore unlikely to play a role in the attenuated responsiveness to estrogen during aging. PMID- 1434944 TI - Expression of c-fos, c-jun and jun B in peripheral blood lymphocytes from young and elderly adults. AB - The expression of c-fos, c-jun and jun B proto-oncogenes was studied in phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) from young and aged humans. Specific mRNAs for c-fos and c-jun were detectable within 30 min after cell activation and reached maximal levels within 2 h. Both c-fos and jun B mRNAs decreased to pre-activation levels within 6 h, while c-jun mRNA remained elevated. In PHA-activated PBL, no age-related differences were observed in c-fos or jun B mRNA expression. However, c-jun mRNA levels decreased significantly (1.73 +/- 0.08 vs. 1.16 +/- 0.09 arbitrary units, P < 0.01, young vs. old) in PBL from elderly individuals activated with PHA. Because previous work has demonstrated that T cells from elderly individuals may display normal proliferative responses when activated via the anti-CD2 pathway, c-jun and jun B mRNA expression was also studied in anti-CD2-activated purified T cells. No age related differences were found in the expression of either of these two proto oncogenes by anti-CD2 activated T cells. These results suggest that the decreased IL-2 production and proliferative response displayed by PHA-activated PBL from elderly adults may be related to age-related changes in c-jun mRNA expression and in the ratio of c-fos to c-jun mRNA. PMID- 1434945 TI - Effect of physical activity stress on the phagocytic process of peritoneal macrophages from old guinea pigs. AB - The different stages of the phagocytic function in peritoneal macrophages from old guinea pigs (27 +/- 3-months-old) were studied before, immediately after and 24 h after being subjected to physical activity stress (swimming until exhaustion) which raised the blood levels of corticosterone. The phagocytosis of opsonized Candida albicans was stimulated immediately after physical activity. No modifications in adherence, chemotaxis, ingestion of inert particles, or microbicide capacity, measured by nitroblue tetrazolium (NBT) reduction, were found. At 24 h, when no stress could be shown by corticosterone analysis, the phagocytosis of opsonized C. albicans remained stimulated and chemotaxis was increased while ingestion of inert particles and microbicide capacity remained unchanged. The adherence, however, was at a smaller level. No correlations were found between the corticosterone levels and the status of the phagocytic process of peritoneal macrophages. PMID- 1434946 TI - Influence of age on stereoselective pharmacokinetics and metabolism of hexobarbital in the rat. AB - The influence of age on stereoselective pharmacokinetics and in vitro metabolism of R- and S-hexobarbital was studied in the rat. After intravenous administration of the racemate, the plasma concentrations of S-hexobarbital are markedly lower than those of R-hexobarbital. For S-hexobarbital the half-life is somewhat shorter and the volume of distribution and plasma clearance is higher than for its antipode. For both enantiomers an increase in AUC and half-life, and a decrease in clearance are observed with aging. These changes occur mainly between the 3rd and the 12th month and are slightly more pronounced for R- than for S hexobarbital, as appears from the S/R ratios. The volume of distribution shows no changes with aging. In vitro disappearance rate in 3-month-old rats is significantly higher for S- than for R-hexobarbital. There is for both enantiomers an increase in disappearance rate in 12-month-old rats as compared to younger or older rats, but this is significant only for the R-enantiomer. There are pronounced differences in the kinetics and metabolism of both hexobarbital enantiomers; changes with aging occur, but are only slightly and not always significantly more important for R- than for S-hexobarbital. PMID- 1434947 TI - Changes with aging and physical exercise in ascorbic acid content and proliferative response of murine lymphocytes. AB - Ascorbic acid content and lymphoproliferative response to phytohemagglutinin were measured in lymphocytes from axillary nodes, spleen and thymus of young (15 +/- 2 weeks) and old (60 +/- 5 weeks) BALB/c mice. Ascorbic acid content in lymphocytes from spleen and thymus was found to be significantly higher and the lymphoproliferative response in the three immunocompetent organs significantly lower in old mice as compared to young mice. Moreover, young and old BALB/c mice were required to maintain a swimming activity until exhaustion (exhaustive exercise) or 90 min of swimming each day for a total of 20 days (continuous exercise). In both young and old mice the stress produced by exhaustive exercise and confirmed by the existence in serum of significantly increased levels of corticosterone compared to controls, caused a significant decrease in ascorbic acid content as well as in lymphoproliferative response. Continuous exercise, characterized by the presence in serum of significantly decreased levels of corticosterone compared to controls, produced the most significant decrease in ascorbic acid content from young and old murine lymphocytes. Moreover, this exercise resulted in a significant increase in lymphoproliferative response. Our results suggest that aging results in an increase in the ascorbic acid content of lymphocytes accompanied by a decline in the lymphoproliferative response in old BALB/c mice. PMID- 1434948 TI - Age-related changes in antioxidant enzyme activities are region and organ, as well as sex, selective in the rat. AB - Enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were determined in the liver as well as several specific brain regions of young and old Fischer-344 rats of both sexes. In the liver of male rats, activities of CAT as well as Mn-SOD were lower, while activities of Cu Zn-SOD were higher in old (30-month-old) rats than in young (7-month-old) ones. Activities of total SOD as well as GSH Px were comparable for young and old male rat livers. In contrast to male rats, in female rat livers, activities of CAT were significantly higher in old (28-months-old) rats, while activities of Mn-SOD were slightly (but significantly) higher in old rat livers. In old male rats, activities of Mn-SOD were significantly higher than in young males in several specific regions of the brain (the substantia nigra (s. nigra), striatum, hippocampus) but lower in the cerebellum. In particular, SOD activities in s. nigra, striatum and hippocampus in old male rats were several fold higher than corresponding values in young male rats. Activities of Cu Zn-SOD were generally unchanged with age. Activities of CAT as well as GSH-Px (both Se-dependent and non-Se-dependent forms) were also relatively unaffected by age. In female rat brains, activities of Mn-SOD as well as those of others all remained mostly unaffected by aging, although there was a general tendency of slightly higher activities in most cerebral regions for Mn-SOD in old female rats. Thus, age related changes of these antioxidant enzymes in the liver and brain are markedly sex dependent and some enzyme activities (such as CAT in the liver) change in an opposite direction with age. Changes of Mn-SOD in the brain were markedly region specific in male rats. Results suggest that the significance of the changes of these antioxidant enzyme activities during aging needs to be carefully interpreted, taking into consideration the fact that changes are markedly variable depending on sex as well as the organs and brain regions examined. PMID- 1434950 TI - Using the Gompertz-Strehler model of aging and mortality to explain mortality trends in industrialized countries. AB - Mortality trends in industrialized countries are characterized by declines in vascular disease (ischemic heart disease and stroke) and rises in cancers and degenerative diseases. These trends are typically analyzed by examining each disorder in isolation using the perspective of genetic and environmental influences. However, longitudinal Gompertzian analysis and the Gompertz-Strehler model of aging and mortality as modified by Lestienne suggest that age-specific mortality rates, for both general and disease-specific mortality, are an interrelated deterministic function of aggregate genetic, environmental and competitive influences. Consequently, evolving mortality trends and patterns appear to be influenced by three factors (with deterministic competition being the third factor), rather than just two factors (genetic and environmental) as commonly depicted. PMID- 1434949 TI - Digoxin cardiotoxicity in aging anesthetized F344 rats. AB - It is generally accepted that the sensitivity to toxic effects of digitalis increases with advancing age; however, the relative contribution of pharmacokinetics and pharmacodynamics to this aging-related change is presently unknown. The current study was designed to determine if senescence affects digitalis tolerance in an animal model and if observed changes are mediated by altered cardiac or autonomic nervous system responsiveness. Male, F344 rats of three age groups (4, 14 and 25 months) were anesthetized and infused intravenously with digoxin at a rate of 880 micrograms/kg per min. Two separate anesthetic regimens were employed: (a) an age-adjusted dose of urethane in spontaneously breathing animals (AR1); and (b) a non-age-adjusted dose of alpha chloralose plus urethane in mechanically ventilated rats (AR2). Heart rate, EKG and arterial blood pressure were monitored continuously; baroreceptor reflex function was estimated before and 10 min following the start of digoxin infusion by examining the response to bilateral carotid occlusion. The infusion time required for digoxin-induced AV-dissociation was significantly reduced by senescence in rats anesthetized by AR1. However, doses of digoxin required to elicit ventricular extrasystoles and death were not significantly different among age groups in this anesthetized model and serum digoxin levels did not differ at the time of cardiac arrest. Similarly, AR2 animals showed a significant aging related decrease in the time to AV-dissociation. However, in contrast to AR1, animals in AR2 displayed an aging-associated increase in the doses of digoxin required to produce ventricular arrhythmias and cardiac arrest. Thus, results suggest that aging in the F344 rat may, by pharmacodynamic mechanisms, promote the sensitivity to digoxin-induced AV-dissociation but not to ventricular arrhythmias or cardiac arrest. PMID- 1434951 TI - Age related rejoining of broken chromosomes in human leukocytes following X irradiation. AB - One theory of aging is that the ability to repair DNA or chromosome damage decreases with age. This study made use of a method which allows the measurement of chromatid repair in interphase nuclei, the technique of premature chromosome condensation. The number of excess chromosome fragments per cell remaining after 24 h of incubation at 37 degrees C was determined and used as a measure of the ability of leukocytes to repair. The leukocytes from male donors of several ages were used and the cells from older donors showed greater residual damage and, therefore, less repair. PMID- 1434952 TI - Age related alterations in the response of the pial arterioles to adenosine in the rat. AB - To evaluate the effects of aging on vasoreactivity of pial arterioles to adenosine and barium chloride, an hydraulically intact cranial window preparation was developed in the rat. The microvasculature of anesthetized 3- and 24-month old Fischer-344 rats was studied during superfusion with artificial cerebrospinal fluid with and without test agents and results determined by videomicroscopy techniques. In both cohorts, the response of pial arterioles to adenosine was both dose and vessel size dependent: arteriolar dilation increased with increasing concentrations of adenosine and at any given concentration the percent increase in diameter was greater in the smaller vessels. During adenosine superfusion the absolute changes and percent increase in vessel caliber were greater in the young rats. Arteriolar vasoconstriction due to barium chloride was vessel size dependent but there were no significant differences in response between young and aged rats. The results indicated an attenuated cerebrovascular response in aged rats to adenosine, but not to barium chloride. This may be due to a difference in the mode of action in these two compounds. Venules did not respond to adenosine at any concentration. PMID- 1434953 TI - Effects of phorbol myristate and ionomycin on in vitro growth of aged Peyer's patch T and B cells. AB - The proliferative responses of Peyer's patch (PP) T cells from aged BALB/c mice to concanavalin A (Con A) are considerably reduced, as compared to those of the young (P < 0.001). This reduced reactivity of aged T cells could be partly, but not entirely, corrected by interleukin 2 (IL-2) (P < 0.001). PP T cells from aged mice responded synergistically to a protein kinase C (PKC) activator, phorbol myristate acetate (PHA), plus a calcium ionophore, ionomycin, at much lower concentrations than to Con A (P < 0.001); however, the maximal proliferative response still remained nearly at 8/10th of the young (P < 0.01) and higher levels of PMA (but not of ionomycin) were required (P < 0.001). Addition of IL-2 restored the diminished response to the levels of the young T cells (P < 0.05), but that of Con A did not (P > 0.05). The proliferative responses of PP B cells to lipopolysaccharide (LPS) do not differ from those of the young (P > 0.05), but the spontaneous proliferation of aged (unstimulated) B cells is enhanced nearly twofold versus that of the young (P < 0.001). Like the PP T cells, PP B cells from aged mice also responded synergistically to PMA plus ionomycin but to a lesser degree than those of the young under the same stimulation (P < 0.01). Their maximal proliferation required higher levels of PMA, but not of ionomycin and was also diminished (P < 0.01), compared to that of the young. B cell stimulatory co-factors, IL-4 and IL-6, failed to affect the response of aged and young B cells to PMA plus ionomycin (P > 0.05), whereas LPS remediates the reduced response of aged B cells to PMA plus ionomycin. Thus, T and B cells from senescent PP demonstrate an impaired proliferative responsiveness via the Ca dependent PKC pathway. A T cell mitogen and B cell stimulatory cytokines did not alter this activation pathway, once optimally stimulated. Whereas, T cell stimulatory cytokine IL-2 and B cell mitogen LPS could restore the age-associated decline of the corresponding lymphocyte subsets, T and B cells, in activation of the Ca-dependent pathway. The altered transmembrane signal transduction appears to be intrinsically defective in these aged PP T and B cells. PMID- 1434954 TI - Difference in response of hepatic glutathione S-transferase activities to protein free diet between young and old C57/BL male mice. AB - Responses of hepatic glutathione S-transferase (GST) activities to protein-free diet (PFD) and normal diet (ND) refeeding were compared for young (6-month-old) and old (22-month-old) C57/BL male mice. Enzyme activities toward 1-chloro-2,4 dinitrobenzene (CDNB) were not significantly different between young and old rat livers in the basal condition without diet manipulation. When animals were fed PFD for 1 week, GST activities toward CDNB significantly declined in both age groups in comparison to respective basal values, but there was no significant difference in activities between the two age groups after a 7-day PFD. When they were refed with ND for 2 days (on day 2 of ND), the activities in young mice rose to a level significantly higher than the corresponding basal value. In contrast, in old animal livers, the activity slightly but further tended to decline on day 2 of ND. Activities in old rat livers returned to the basal level on day 5 of ND, while activities in young animal livers that increased to levels higher than basal levels due to the overshoot returned to the basal level on day 7 of ND. Enzyme activities toward 1,2-dichloro-4-nitrobenzene (DCNB) were significantly higher in young rat livers than in old ones at the basal period. However, enzyme activities also overshot the basal level on day 2 of ND after 7-day PFD in young mouse livers, while in old mouse livers the activities were lowest on this day. Activities returned to the basal level on day 7 of ND in both age groups. Thus, the greatest difference in enzyme activities between young and old mouse livers for both substrates was observed on day 2 of ND after 7-day PFD, rather than at either the basal period or immediately after 7-day PFD. The results essentially agree with our previous findings on female C57/BL mice as well as female Fischer 344 rats, suggesting that the age-induced changes in the GST system become clearly manifest after diet manipulation of PFD followed by ND refeeding, rather than in values during a basal period without diet manipulation, regardless of sex or species of animal. PMID- 1434955 TI - Assigning appropriateness ratings for diagnostic upper gastrointestinal endoscopy using two different approaches. AB - Methods that combine information in the medical literature with expert clinical judgment are needed to determine the appropriateness of use of a procedure. The purpose of this study is to better understand the reliability and construct validity of this process by comparing ratings of appropriateness for diagnostic upper gastrointestinal endoscopy that were developed using different approaches by two independent groups. Both the RAND/UCLA Health Services Utilization Study (HSUS) and the American Society for Gastrointestinal Endoscopy (ASGE) combined scientific data with expert physician judgment to rate the appropriateness of specific clinical indications for the use of upper gastrointestinal endoscopy. This study applies the ratings developed by each group to a nationally representative sample of 1,585 endoscopies performed on people 65 years of age and older in 1981. HSUS developed indications that could be used to rate all 1,585 procedures; ASGE indications were less comprehensive and applied to 70% (n = 1,115) of procedures. Of those rated by both groups, appropriateness category ratings agreed for 94% of the procedures. However, the procedures not rated by ASGE were unevenly distributed across HSUS appropriateness ratings. Twelve percent of procedures rated as appropriate by HSUS were not rated by ASGE, but 80% of procedures rated as equivocal by HSUS and 73% rated as inappropriate by HSUS were not rated by ASGE, for those procedures rated by both approaches there was good agreement; however, a more explicit and comprehensive method may be required if equivocal and inappropriate use of a procedure is to be identified. PMID- 1434956 TI - Adherence to screening flexible sigmoidoscopy in asymptomatic patients. AB - The purpose of this study was to assess patient adherence to physician recommended screening flexible sigmoidoscopy. In the setting of a family practice residency program, adherence rates in asymptomatic patients (N = 333, age > or = 50 years) were compared among a Usual Care Group; an Intervention Group that received educational materials and a phone reminder; and a Continuity Group, which had longstanding continuity with a single physician. Data from mailed questionnaires (N = 180) were used to examine the associations of demographic factors and attitudes with adherence. Adherence was 30.3% overall, with a nonsignificant increase in the Intervention Group compared with the Usual Care Group. In a pooled analysis of the Usual Care and Continuity Groups, the half of the sample with the highest continuity had a significantly higher adherence rate than the rest of the sample (45%; P < 0.001). In a discriminant analysis (78% correct classification, P < 0.001) two history variables (family history of cancer; family history of colon problems), one measure of continuity (number of physician visits), one demographic variable (lower household income), and two attitudinal factors (perception of how painful flexible sigmoidoscopy would be; perception of how well the physician explained its importance) made statistically significant contributions to the prediction of adherence. Results of the study show that screening flexible sigmoidoscopy is acceptable to asymptomatic patients, and that continuity is likely to have a positive impact on adherence. Because attitudes offer the potential for modification, we suggest that physicians reassure patients that flexible sigmoidoscopy is not unduly painful and discuss with patients individually its importance to their health. PMID- 1434957 TI - Utilization review savings at the micro level. AB - Utilization review (UR) programs have become an integral part of efforts to contain health care costs for private health insurers, employers, and health care organizations. While some studies have measured the overall performance of these programs, important information in the prior level of the health care utilization has not been used in estimating the effectiveness of the program for micro units (e.g., employer groups). In this article, the authors present a model to determine how the impact of the hospital UR program on health care utilization for specific groups varies with historical use patterns. The estimation approach used in this article can be used to determine the effect of UR for specific employer groups without having to rely on the average effectiveness measures for all. Claims obtained from Aetna Health Plans provided data for more than 5,300 employer accounts covering approximately 580,000 employees, 44% of whom had the UR program sometime during the period 1987 to 1990. Because of regression to the mean, UR savings were greater for units with higher prior use and smaller for units with lower use. In addition to prior use, the size of the group also determined the extent of regression to the mean. Groups with smaller number of enrollees had greater potential to save from the UR because of UR's ability to reduce the outliers. PMID- 1434958 TI - State border crossing for Medicare hospital admissions. PMID- 1434960 TI - The risk of adjustment. PMID- 1434959 TI - Some methodological lessons for surveys of persons with AIDS. PMID- 1434961 TI - Analyzing communication in medical consultations. Do behavioral measures correspond to patients' perceptions? AB - When analyzing relationships between physician-patient communication and medical outcomes, researchers typically rely on quantitative measures of behavior (e.g., frequencies or ratios) derived from observer-coding of transcripts, audiotapes, or videotapes. Interestingly, rarely have researchers assessed whether quantitative measures of communication (e.g., the physician's information giving) correspond to patients' perceptions of physicians' communication (e.g., informative). This investigation of 115 pediatric consultations examined this issue and yielded several notable findings. First, less satisfied parents received more directives and proportionally less patient-centered utterances from physicians than did more satisfied parents. Second, findings were mixed regarding the degree to which behavioral measures related to analogue measures of parents' perceptions. For example, the doctors' use of patient-centered statements was predictive of parents' perceptions of physicians' interpersonal sensitivity and partnership building, but the amount of information physicians provided parents was unrelated to judgments of the doctors' informativeness. Third, with some important exceptions, relationships between behavioral measures and parents' evaluations did not vary for parents differing in education and anxiety about the child's health. Finally, behavioral measures in the form of frequencies tended to be better predictors of parents' perceptions than were measures in the form of proportions. Implications are discussed. PMID- 1434962 TI - The effects of consultation on over-the-counter medication purchasing decisions. AB - This article examines factors that predict changes in consumer purchasing decisions of nonprescription medications. Variables corresponding to factors in Andersen's behavioral model are measured, in addition to data regarding characteristics of the 17 pharmacy consultants who provided counseling services. One thousand seven hundred and thirteen consumers in five stores in southern California were provided consultation during a 6-month period, resulting in 25.4% of the patients purchasing a different drug than intended when entering the pharmacy, 1.3% being referred to a physician, and 13.4% not purchasing any over the-counter medication at all. Logistic regression techniques demonstrated that one enabling variable (availability of generic medications), and four need factors (the discussion of clinical issues, short encounters, cough and cold products, and vitamin products) were significant predictors of the consumer's decision to purchase a different product than intended. Consultant characteristics (introversion, external locus of control) were also important predictors, but opposite the expected direction. Consumers who received information from female consultants were more likely to change their purchasing decisions. PMID- 1434963 TI - An overview of the development and refinement of the Resource-Based Relative Value Scale. The foundation for reform of U.S. physician payment. AB - Responding to distortions in payment rates between services, policymakers in the United States have sought a systematic and rational foundation for determining physician fees. One such approach to paying physicians, the Resource-Based Relative Value Scale (RBRVS), determines fees by measuring the relative resource costs required to produce them. On January 1, 1992, the Medicare program implemented a new payment system for physician services based on the RBRVS. This article provides a brief history of the RBRVS and a summary of the methods and data used to derive it. This overview represents the culmination of 6 years of research by the Harvard RBRVS study team and provides a road map to the study's concepts and definitions. The overview also provides a context for the articles in this issue that describe five major studies undertaken since 1988. The study's overall results are presented in the last article of the series. PMID- 1434964 TI - Predicting the work of evaluation and management services. AB - Physicians, carefully adhering to the definitions of Physicians' Current Procedural Terminology (CPT) billing codes, used the same CPT codes to denote evaluation and management services that varied widely in work and used different codes for services whose work was the same. As payment shifted to the Medicare Fee Schedule, it was important that the coding system be redefined so that codes consistently reflect the resource costs of these services. Redefining these codes for a resource-based payment system required an understanding of how verifiable predictors relate to physician work. Using data obtained from the Resource-Based Relative Value Scale (RBRVS) study regarding 377 services surveyed among physicians in 31 specialties, multiple regression analyses of the relationship of different variables to the mean values of work were performed. Intraservice time, which accounted for 90% of the variance, was the most important predictor of intraservice work. Specification of time, which previously had not been an element in the definitions of CPT codes for evaluation and management services, was useful in refining these codes so that their value corresponds more closely to resource costs. Other predictors of work were site of service or visit type, patient status (new/initial, established/subsequent), and referral status (consultation, nonconsultation). PMID- 1434965 TI - Small-group judgment methods for determining resource-based relative values. AB - National telephone surveys used in the Resource-Based Relative Value Scale Study produce reliable and valid relative values of work, but phone surveys are expensive and time consuming. We evaluated three small-group processes as alternatives. We compared national survey work estimates for 38 surgical services to those generated by panels of 11 and 19 highly qualified general surgeons using 1) single-round mail survey; 2) Delphi multiple-round ratings; and 3) modified Delphi with face-to-face discussion. Single-round mail-survey ratings were closest to the national survey; average differences were 11.0% and 12.6%. Delphi feedback led to increased differences: typical values differed by 14.6% and 15.2%. Face-to-face discussion led to still further divergence (21.0%). Single round mail survey of a small number of experts provides relative work values that compare more favorably to those of the national survey than those obtained from Delphi multiple-round ratings or modified Delphi with face-to-face discussion. PMID- 1434966 TI - Physician and practice characteristics, frequency of performance, and the Resource-Based Relative Value Scale. AB - The Resource-Based Relative Value Scale is based in part on the ratings of the work of services obtained from a random sample of physicians in a specialty. Ratings are used without regard to board-certification or other characteristics of the physician, or to the physician's experience with the service. Critics have suggested that all physicians may not be equally qualified to rate the work of services. Using data obtained from the Resource-Based Relative Value Scale surveys and analyzed using multiple regression methods, the authors found that physician and practice characteristics explain, at most, a small fraction of the variation in ratings of work. Any increase in the precision of the work scale obtained by adjusting physicians' work ratings according to physicians' characteristics could be achieved at lower cost by a slight increase in sample size. Associations between frequency of performing a service and ratings of work are about as likely to be in one direction as another. Most of the differences between estimates of work, excluding and including physicians who have not performed a service, are less than 2% in absolute value, and all are less than 10%. Estimates of work using ratings of physicians in the upper half in frequency of performance are usually within 10% of estimates using other ratings. Even if the observed associations are not due to chance, the potential improvement in accuracy of estimates of work appears too small to justify using data on frequency of performance. PMID- 1434968 TI - Results and impacts of the Resource-Based Relative Value Scale. AB - On January 1, 1992, the Health Care Financing Administration implemented the 1989 legislation reforming the Medicare payment system for physicians' services. The cornerstone of the new payment reform is the Medicare Fee Schedule (MFS), which is based on the Resource-Based Relative Value Scale (RBRVS). In this article, the major findings of the RBRVS study and its impacts on physician payment are summarized. The authors report the impacts of a RBRVS-based fee schedule on Medicare fees and physicians' income if it were fully implemented, assuming budget neutrality and absence of volume changes in services. Under this scenario, fees for evaluation and management services increase by 15% to 45%, while fees for invasive services and diagnostic tests decrease by 20% to 30%. These changes increase the Medicare income of family practitioners by more than 30% while decreasing the income of most surgical specialties by 10% to 20%. PMID- 1434967 TI - Incorporating practice costs into the Resource-Based Relative Value Scale. AB - Practice costs (not including liability insurance costs) account for approximately 41% of the payment for medical and surgical services in the Medicare Fee Schedule. Unlike the portion of the fee schedule that compensates physicians for their work, the practice cost portion of the Medicare Fee Schedule is not resource-based; it is based instead on historical charges. As a result, physicians can recover their practice costs in less time and with less effort (measured in work relative value units) by performing invasive procedures and tests than by providing evaluation and management services. The Physician Payment Review Commission has proposed, in some detail, a method for incorporating practice costs into the Medicare Fee Schedule. The method involves allocating indirect costs on the basis of physician work plus direct costs. We find, using their own analytical framework, that indirect costs should rather be allocated on the basis of time. But to better serve the goal of incentive neutrality, and to make practice cost payments more equitable, the payment a physician receives for practice costs should be based not on service mix and volume, but on characteristics of the physician's practice more closely related to practice costs: for example, whether the physician has an office, or whether the physician practices alone or in a group. PMID- 1434969 TI - Understanding the Medicare Fee Schedule and its impact on physicians under the final rule. AB - On January 1, 1992, the Medicare program unveiled a new method for paying physicians known as the Medicare Fee Schedule (MFS). The new fee schedule is a complex system of administrative pricing based on the resource inputs used in producing physician services. The MFS consists of three parts: 1) a Relative Value Scale, which assigns to each medical service a value relative to all other services; 2) a conversion factor, which converts the relative values into dollars; and 3) a geographic adjustment factor, which adjusts payments based on geographic differences in the cost of producing physician services. In this article, the following are addressed: how the relative values were determined; how the geographic adjustment factor was constructed; and how the conversion factor was calculated. In addition, balance billing limits and the Medicare Volume Performance Standards (MVPS) are described. Computer simulations of the impact of the MFS on payments to physicians are presented. The authors found that the MFS will 1) redistribute payments away from surgeons, radiologists, and other procedure-based specialties toward the primary care specialties; 2) redistribute payments away from urban areas toward rural areas; and 3) redistribute payments away from invasive procedures and diagnostic tests toward evaluation and management services. The authors conclude with a discussion of the future refinements of the MFS, its applicability to other payers, and whether it will accomplish its intended purposes. PMID- 1434970 TI - [Comparative study of the survival of gastric B-cell lymphoma of mucosal origin with respect to lymph node lymphoma of similar histology]. AB - BACKGROUND: The differences in clinical presentation, morphology, phenotype and genetic changes between lymphomas originating in the gastrointestinal tract and the lymph nodes justified the proposal of a system of specific classification for lymphomas originating in lymphoid tissue associated to mucosa (MALT). Nevertheless, there is no conclusive evidence that the types of lymphoma defined as such have a different clinical evolution with respect to the lymph nodes lymphomas. METHODS: With the aim of analyzing this problem a clinical follow up of 33 patients with primary gastric lymphomas (high and low grade) was compared with the results of a group of 99 lymphomas of the lymph nodes was carried out with classification according to the criteria of Kiel classification and the proposal by Isaacson et al for MALT lymphomas. Survival obtained by the Kaplan Meier method was compared by the Mantel-Haenzel test. RESULTS: The results obtained showed that all gastric lymphomas have a less aggressive evolution than those of lymph node origin (p < 0.01). This significant statistical difference was also observed when lymphomas of similar histology were compared. Similarly, the subgroups of large cell lymphoma (p < 0.05) and small cells (p < 0.01) differ with respect to lymphomas of similar histology and of lymph node origin. In contrast with the results expected, no significant difference was observed between the two main groups of lymphomas of high and low grade mucosal origin. CONCLUSIONS: The analysis of the results supports the convenience of a system of specific classification for lymphomas of mucosal origin. Nevertheless, the specific existence of groups of high and low grade lymphomas is questioned since the probability of survival between both subgroups does not show statistically significant differences. PMID- 1434971 TI - [Primary gastrointestinal lymphoma: a study of 25 cases]. AB - BACKGROUND: The digestive tract constitutes the most frequent localization of the extranodular non Hodgkin's lymphoma. The chief clinical and histological characteristics were analyzed as were the evolution and response to treatment of 25 patients diagnosed with primary gastrointestinal lymphoma (PGIL) in one center over a period of eight years. METHODS: To establish the diagnosis of PGIL the Dawson criteria were used and the state was determined by the Ann-Arbor classification modified by Musshoff. To histologically classify of the PGIL the Working Formulation was followed. The influence of the clinical, histological characteristics and the state of the obtention of complete remission (CR), the survival free period of the disease (SFD) and global survival (GS) were analyzed. RESULTS: The mean age of the series was 56 years (standard deviation 15 years) (12 males). The most frequent localization was gastric followed by the small intestine and the large intestine. Abdominal pain and weight loss were the most frequent clinical manifestations in the PGIL, regardless of its site. In 12 patients the PGIL was of an intermediate grade of malignancy, 8 were of low grade and 5 of high grade. The state was IE in 11 patients, IE1 in 9 and IIE2 in 5. The most used treatment was radical surgery followed by polychemotherapy. Complete remission was obtained in 15 patients and 2 recurred. The foreseen SFP at 7 years was 69% of the cases and GS was 53%. In IE state patients was most frequently obtained and GS was also more prolonged in these patients. CONCLUSIONS: In the present series the gastric localization of patients with primary gastrointestinal lymphoma was more frequent than intestinal localization. The HNL of intermediate and high grades of malignancy predominated those of low grade. The prognosis of patients with primary gastrointestinal lymphoma in a IE state was more favorable than the remaining patients. In turn, surgery constituted a good option in the initial treatment of patients with primary gastrointestinal lymphoma. PMID- 1434972 TI - [Sudden cardiac death in the counties of Girona]. AB - BACKGROUND: Data on sudden cardiac death in Spain in scarce. Mortality rates from sudden cardiac death occurring in six counties of Girona (including urban, industrial, and rural areas) between October 1987 and September 1988 were assessed. METHODS: From a total of 1,573 deaths in residents of the studied area aged between 25 and 74 years, 222 cases with a suggestive diagnosis of sudden cardiac death were selected. Data that confirmed the diagnosis and the time elapsed from the initial clinical symptoms and death were obtained by inquiring physicians who signed the death certificates, relatives or witnesses and by reviewing the hospital records. RESULTS: Of a total of 137 deaths of cardiac origin, there were 107 cases of sudden cardiac death (which occurred within 24 hours after the onset of symptoms). The mortality rate of sudden death of cardiac origin was 37.5 per 100,000 inhabitants, that was significantly higher among men (67.8 in men and 15.4 in women). The mortality rate showed a statistically significant increase in the older age groups (28.4 per 100,000 inhabitants in the age group of 45-54 years, 69 in the group of 55-64 years, and 129.7 in the group of 65-74 years). Death occurred within the first hour after the onset of symptoms in 59 patients, 17 of whom were admitted to a hospital. Only 35% of the total 107 patients were treated in hospital. CONCLUSIONS: Mortality rate of sudden cardiac death in Girona is low. Few patients dying from sudden cardiac death could have medical care. PMID- 1434973 TI - [Bacterial peritonitis in cirrhosis. Prospective study of 80 episodes]. AB - BACKGROUND: The high incidence, recognition of the different variants and the important changes introduced in the methods of diagnosis of bacterial peritonitis of cirrhotic patients led the authors to study this entity according to the most up to date and standardized criteria. METHODS: The clinical-epidemiological, biological and bacteriological characteristics of 80 episodes of ascitic fluid infection (AFI) were studied. Diagnostic paracentesis was performed in all the patients and were evaluated according to a prospective study protocol. RESULTS: The patients with AFI were classified into three groups: 1) spontaneous bacterial peritonitis (SBP) (761 episodes); 2) secondary bacterial peritonitis (BP) (5 cases); and 3) bacteriascitis (BA) (4 episodes). The clinical manifestations were not specific, with absence of abdominal pain and fever in 9% of the cases. There were no clinical differences between the variants of AFI. The ascitic fluid culture was positive in 80% of the cases of SBP while it was only so in 9% of the Gram stain. Most of the cases of peritonitis were caused by Gram negative bacilli (77%), predominantly E. coli (64%). The culture was positive in 100% of the cases of BP, generally being polymicrobian, and Gram stain was positive in 67% of the cases. The inflammatory response of the ascitic fluid in the different variants of AFI was gradual, being lower in BP and nul in BA. In 52 episodes of SBP (73.8%) the infection was cured. In the group of SBP all the patients died without having resolved the peritonitis (p < 0.001). Forty-four patients (62%) with BP were discharged from hospital. A multivariate logistic regression analysis demonstrated that from a total of 32 variables analyzed, only the absence of fever (p < 0.0001), the presence of advanced hepatic encephalopathy (p < 0.0001), the presence of leukocytosis, serum bilirubin higher than 137 mumol/l, urine sodium levels lower than 10 mmol/l, the level of LDH in ascitic fluid higher than 2 microKat/l and ascitic fluid culture positivity had independent prognostic value. CONCLUSIONS: Infection of ascitic is a frequent entity. Although its variants are clinically indifferentiable, there are clear biochemical, bacteriological and evolutive differences. The mortality of ascitic fluid infection remains high. Its prognosis fundamentally depends of the degree of evolution of the hepatopathy and the severity of the peritoneal infection. PMID- 1434974 TI - [Primary gastrointestinal lymphomas]. PMID- 1434975 TI - [The hospital, a competitive and efficient health care organization]. PMID- 1434976 TI - [Genetic markers in neuropsychiatric disorders: genetic mapping and diagnostic and therapeutic prospectives (I)]. PMID- 1434977 TI - [Changes in the prevalence of anti-HCV in blood donors in Asturias]. PMID- 1434978 TI - [Immunoblastic lymphoma associated with IgA paraproteinemia as a complication of a case of pediatric AIDS]. PMID- 1434979 TI - [Cerebral infarction as the initial manifestation of mediterranean spotted fever]. PMID- 1434980 TI - [Acute hepatitis from A virus in carriers of HBsAG superinfected by the hepatitis C virus and the human immunodeficiency virus]. PMID- 1434981 TI - [Is the administration route of heroin changing?]. PMID- 1434982 TI - [Cutaneous metastasis as a presenting form of lung carcinoma: 2 new cases]. PMID- 1434983 TI - [Extrahepatic cholestasis in a patient with Kaposi sarcoma associated with the acquired immunodeficiency syndrome]. PMID- 1434984 TI - [Immunologic prognostic parameters in infection by the human immunodeficiency virus]. AB - BACKGROUND: To evaluate the use of quantitative and functional immunologic parameters as prognostic markers of infection by the human immunodeficiency virus (HIV). METHODS: The number of CD4 and CD8 lymphocytes, the CD4/CD8 ratio, the percentage of interleukin 2 (IL-2) receptors, the response to phytohemaglutinin (PHA) and the production of interferon tau (IFN-tau), were analyzed in 85 patients with HIV infection: 14 with acquired immunodeficiency syndrome (AIDS) (stage IV), 16 with persistent generalized adenopathies (stage III), and 55 asymptomatic patients (stage II). Similarly, a control group of 35 blood donors with negative HIV serology was studied. RESULTS: Over a period of 30 months, 17 patients (5 of stage III and 12 of stage II) evolved to stage IV. In a multivariate analysis the decrease in the number of CD4 lymphocytes in stage II and the decrease in the production of IFN-tau in stage II and III were the parameters associated with progression to stage IV. CONCLUSIONS: The decrease in the production of interferon tau in patients with infection by the human immunodeficiency virus in stage II and III as well as the decrease in the number of CD4 lymphocytes in stage II are prognostic factors associated with the evolution to stage IV of the infection. PMID- 1434985 TI - [Comparative study of human cutaneous sensitivity to 2 and 5 international units of the PPD RT 23 tuberculin with Tween 80]. AB - BACKGROUND: The aim of this study was to know whether the human reaction to the Mantoux test with 5 UT of PPD RT 23 is similar to that achieved with the same test but with 2 UT of the same substance. METHODS: A simultaneous double Mantoux test was used at doses of 2 UT and another of 5 UT of the same trade mark of tuberculin PPD RT 23 with Tween 80 in 2,575 individuals. The subjects were distributed into two different groups of different ages, taking into consideration the possible presence of BCG vaccination. RESULTS: The doses of 5 UT produced a greater number of tuberculin positive individuals and a greater diameter of induration of reaction than that of the doses of 2 UT in both groups and with significant statistical differences. One hundred ninety-six (7%) subjects were tuberculin positive with 5 UT and negative with 2 UT. CONCLUSIONS: The reactions produced by the Mantoux test with 5 and 5 UT PPD RT were different since the two doses are not bioequivalent. PMID- 1434987 TI - [Atherogenesis. The lipidic hypothesis updated]. PMID- 1434986 TI - [Clinical application of the biological variability data of the thyroid hormones]. AB - BACKGROUND: The selection of laboratory tests with greater effectiveness for identifying patients with thyroid disorders (sensitivity) from non affected subjects (specificity) is, at present, under discussion. The study of biological variation can contribute to point out the laboratory tests with greater effectiveness. METHODS: Total blood was collected daily for five consecutive days from 25 healthy volunteers, which maintaining their usual life style all over the period. RESULTS: The biological coefficients of variation--within and between- subject, the individuality indexes and the critical differences between consecutive results are estimated. The effect of pulsatility over the results obtained is also discussed. CONCLUSIONS: The most effective laboratory test for the diagnosis of thyroid disorders is TSH, with the precaution of doing a second analysis if the first result falls close to either the lower or higher reference range limits. The best laboratory tests for the monitoring of hypo- and hyperthyroidism are total T4 and free T4, in which a critical difference between consecutive results higher than 15% indicates a significant change in the patient status. PMID- 1434988 TI - [Progress in the treatment of auricular fibrillation. Cure is pending]. PMID- 1434989 TI - [Can a prostatic adenocarcinoma simulate an acute myocardial infarction?]. AB - The assay for the MB isoenzyme of creatine kinase is widely used in the diagnosis of acute myocardial infarction. Patients with metastatic carcinoma of the prostate may have an elevated serum creatine kinase BB fraction, which by immunoinhibition method may be read mistakenly as creatine kinase MB. We report the case of a patient with a history of myocardial injury, chest pain, total CK above of reference range and CK-MB isoenzyme, determinated with an immunoinhibition technique, larger than 100% of enzymatic activity of total CK, that was carrier of a prostatic adenocarcinoma in stage D2. We comment the diseases in which the CK-BB fraction may be elevated, discuss the laboratory methods for the determination of creatine kinase isoenzymes, and revised, briefly, the properties of the new immunoassays, that measure mass concentration of creatine kinase MB, in the diagnosis of acute myocardial infarction. PMID- 1434990 TI - [Serum lipoprotein (a) levels during treatment with LDL apheresis for homozygous familial hypercholesterolemia]. AB - BACKGROUND: Due to the double atherogenic and antifibrinolytic action of lipoprotein (a) (Lp [a]) and its predictive value of cardiovascular disease in hypercholesterolemic patients, we document in the present work the changes in Lp (a) levels of a patient with homozygous familial hypercholesterolemia after one year of LDL-apheresis treatment. METHODS: A child with LDL-receptor deficiency under weekly LDL-apheresis treatment with dextran-sulfate columns. Serum samples were taken in basal conditions (pre-apheresis) and post-apheresis, as well as from the perfusion system to evaluate the lipoprotein retention capacity of the columns. Samples were processed for Lp (a) determination by ELISA with polyclonal antibodies. RESULTS: When the treatment was initiated, the patient's Lp (a) serum levels were very high (997 mg/l), and they reduced progressively with the apheresis sessions. After one year of treatment, maximum Lp (a) concentration is only slightly higher than 400 mg/l, whereas minimum Lp (a) concentration is lower than 50 mg/l. Dextran-sulfate columns in the apheresis system retain every lipoprotein containing apo B, including LDL and Lp (a), with high affinity and high capacity in such a way that the treatment of three-fold the plasma volume of the patient results in an 85% decrease of Lp (a) levels. After each LDL-apheresis treatment, there is a progressive increase in Lp (a) concentration. The analysis of these data allowed the estimation of the fractional catabolic rate of Lp (a) in the patient, which was 0.08 pools/day. Simultaneous treatment with lovastatin (20 mg/day) did not alter this parameter or Lp (a) serum concentration. CONCLUSIONS: After one year of weekly LDL-apheresis treatment, the patient's average Lp (a) serum concentration is lower than 300 mg/l, which is below the risk threshold level. Therefore, apheresis with dextran-sulfate columns is a very effective treatment for the reduction of both LDL and Lp (a) serum concentrations in homozygous familial hypercholesterolemia. PMID- 1434991 TI - [Thalidomide and graft verses host disease: basis for a new indication and side effects]. PMID- 1434992 TI - [Stress ulcers: physiopathology, prophylaxis and treatment]. PMID- 1434993 TI - [Neuralgia of the trigeminal secondary to lipoma of the pontocerebellar angle]. PMID- 1434994 TI - [Eosinophilic pleuritis as the presenting form of sarcoidosis]. PMID- 1434995 TI - [Treatment with a derivative of propamidine for keratitis in a user of soft lenses]. PMID- 1434996 TI - [The Spanish translation of the 3rd edition of "Uniform requirements for manuscripts submitted to biomedical journals"]. PMID- 1434997 TI - [Ferrokinetic studies in the initial evaluation of idiopathic myelofibrosis: results in 18 patients]. AB - BACKGROUND: Since there is no effective treatment for idiopathic myelofibrosis (IM) the determination of possible factors which are involved in the appearance of anemia in this disease may be important from a practical point of view. METHODS: The results of the initial ferrokinetic study analyzed in 18 patients with IM included plasma clearance (T1/2) and globular incorporation (U max) of 59Fe in addition to the uptake of 59Fe in the sacrum, spleen and liver in 16 patients. The clinical-hematologic and histologic data of the different groups of patients identified according to the results of the study were compared. RESULTS: Three ferrokinetic patterns were observed: 1) normal or increased erythropoiesis (8 patient), 2) inefficient erythropoiesis (7 patients), and 3) aplastic pattern (3 patients). The only difference observed between the three groups was the existence of lower levels of Hb and reticulocytes in the subjects with aplastic type pattern. In contrast, although there was an inverse correlation between the medullar and extramedullar uptake of iron (p = 0.018) no relation was observed between the latter and the size of the spleen or liver. CONCLUSIONS: The results obtained in this study indicate that IM behaves heterogeneously from a ferrokinetic point of view. PMID- 1434998 TI - [Haemophilus influenzae pulmonary infection in patients infected with the human immunodeficiency virus]. AB - BACKGROUND: Haemophilus influenzae has frequently been identified as the etiologic agent in pneumonias of patients with the human immunodeficiency virus (HIV) infection. The experience of the authors is reviewed and the significance of isolating this microorganism in respiratory samples commented upon. METHODS: The clinical, radiological and microbiological data of patients with HIV infection in whom H. influenzae was identified in blood, lung tissue, or samples of the lower respiratory tract obtained by fibrobronchoscopy were retrospectively evaluated. RESULTS: Twenty cases were diagnosed with 75% presenting bilateral lung infiltration. In 70% the isolation sample was that of bronchoalveolar lavage. In 40% of the total another microorganism was identified in coinfection with H. influenzae, of which Mycobacterium tuberculosis was the most frequent. Thirty-five percent of the cases presented antecedents of one or several previous pulmonary infections. H. influenzae infection was not observed with either concomitant or previous infections in 20% of the patients. CONCLUSIONS: A high frequency of pneumonias by Haemophilus influenzae with bilateral radiologic presentation have been found. H. influenzae is frequently demonstrated as in coinfection with other agents. The role that this microorganism has in pulmonary infection of patients with HIV infection is not clearly defined. PMID- 1434999 TI - [Cost-effectiveness study of prevaccination screening tests in vaccination against hepatitis B in hospital health professionals]. AB - BACKGROUND: The aim of this study was to know the cost-effectiveness of a vaccination program of hospital personnel against hepatitis B as compared to vaccination strategy with previous screening tests versus vaccination without screening. METHODS: The costs of the process of vaccination with and without previous screening tests for hospital personnel (first year residents = MIR R1 and staff doctors) was calculated taking, not only the cost of the vaccinations, but also the costs of withdrawal, injection, antibody determination and the displacement costs of the subject into account. RESULTS: In the case of a MIR-R1, the cost of vaccination without previous screening is 12,492 pesetas, with the cost for a staff doctor being 15,092 pesetas. The vaccination strategy with previous antibody screening tests is only profitable with prevalences of 28.77% of positivity in the case of MIR-R1 and 29.55% in staff doctors. CONCLUSIONS: This study defends the elimination of previous antibody screening tests in vaccination against hepatitis B since the legal obligation of previous screening tests is no longer applicable. Moreover, vaccination is practically innocuous and prevaccination screening tests are only profitable with prevalences os seropositivity higher than 28% in the case of MIR-R1 and 29.55% in the case of staff doctors which are ciphers much higher than those of the prevalence of seropositivity normally found among Spanish hospital personnel. PMID- 1435000 TI - [Contribution of magnetic resonance imaging in the early diagnosis of epidural metastasis]. AB - BACKGROUND: Vertebral bone metastases represent the most frequently affected region within the skeleton. They are of important relevance because of the risk of medullar compression. The diagnosis of medullar canal invasion is of particular interest in order to prevent neurological dysfunction. A prospective study was carried out to detect the frequency and degree of invasion of the spine. METHODS: Twenty-eight patients were studied (13 males and 15 females), with a median age of 61 years (range 35-85), with cancer diagnosis and vertebral bone metastases, and local or radicular pain, without signs or symptoms suggesting myelopathy. Neurological, physical examination, radiological study (anteroposterior and lateral) and magnetic resonance imaging (MRI) study was performed in all patients to detect medullar canal invasion. RESULTS: Local pain was present in 43% of patients (n = 12), and radicular in 57.1% (n = 16). The most frequent radiologic vertebral involvement was thoracic (46.4%), with 71% of vertebral body collapse. MRI showed epidural space invasion in 75% of patients (n = 21), with a degree superior to 50% in 43%. CONCLUSIONS: The beginning of vertebral pain in a patient with cancer diagnosis, with evidence of bone invasion after radiological study, represents a major indicator to perform a MRI study to detect epidural involvement. PMID- 1435001 TI - [Effects of captopril on left ventricular morphology and function in essential arterial hypertension]. AB - BACKGROUND: The presence of diastolic dysfunction in a hypertensive patient is not necessarily associated to the existence of left ventricular hypertrophy. The aim of this study was to determine whether the reduction of the left ventricular mass in hypertensive patients treated with captopril is accompanied by an improvement of the diastolic filling indexes. METHODS: Nineteen patients with essential hypertension were studied before and after one year of treatment with captopril. Different morphological indexes and diastolic function of the left ventricle were evaluated by mode M and Doppler echography. RESULTS: The indexes of left ventricular mass diminished significantly with treatment with captopril. The thickness of the ventricular walls diminished with treatment although not significantly. No significant modification was observed in the indexes of diastolic function (quotient of speed of protodiastolic filling/speed of telediastolic filling and time of deceleration of transmitral fluid during diastole) following the treatment period. CONCLUSIONS: Diminution of the left ventricular mass induced by captopril in hypertensive patients is not accompanied by an improvement in ventricular filling. It is suggested that myocardial hypertrophy is not responsible for diastolic dysfunction of arterial hypertension. PMID- 1435002 TI - [Etiology of infantile cerebral paralysis]. PMID- 1435003 TI - [Anovulatory agents and changes in hemostasis]. PMID- 1435004 TI - [Acute transverse myelitis and primary antiphospholipid syndrome]. AB - The case of a 39 years old woman with acute transverse myelitis manifested as a syndrome of the anterior spinal artery is presented. Etiologic investigation diagnosed a primary antiphospholipid syndrome because of the finding of significantly high titers of anticardiolipin antibodies discarding the presence of systemic lupus erythematosus for the lack of sufficient diagnostic criteria. The association between both clinical pictures is infrequent. PMID- 1435005 TI - [Multifocal motor neuropathy after administration of gangliosides]. AB - A case of a 38 years-old male with motor neuropathy with multifocal conduction blocks following the administration of ganglioside therapy is reported. There was generalized weakness without areflexia and normal parameters of the spinal fluid, including protein values. Electrophysiological data showed multiple conduction blocks with normal nerve conduction velocities. Antibodies against asialo-GM1 gangliosides were present in the cerebrospinal fluid. There could be a relationship between the ganglioside administration and the development of an immune-mediated neuropathy. Several cases of demyelinating polyradiculoneuritis after ganglioside treatment have been reported. If this association is confirmed, the apparent lack of toxicity of gangliosides should be reconsidered. PMID- 1435006 TI - [Perspectives in the treatment of cancer]. PMID- 1435008 TI - [Are DNA probes useful for the diagnosis of Mycoplasma++ pneumoniae pneumonia?]. PMID- 1435007 TI - [Genetic changes in carcinoma of the colon]. PMID- 1435009 TI - [Auricular fibrillation in organophosphate poisoning]. PMID- 1435010 TI - [Lymphangioleiomyomatosis. Evolution of the same problem]. PMID- 1435011 TI - [Lymphoma and orbital involvement]. PMID- 1435012 TI - [Prevalence of antibodies against hepatitis C virus in HIV positive subjects from different risk groups]. PMID- 1435013 TI - [Pleural empyema in Legionella pneumophila nosocomial pneumonia in a patient with systemic lupus erythematosus]. PMID- 1435014 TI - [Arthritis reactive to Giardia lamblia]. PMID- 1435015 TI - [Tuberculous infection in health personnel]. PMID- 1435016 TI - Modulation of potassium channels by organic molecules. PMID- 1435017 TI - The role of cytokines in muscle wasting: its relation with cancer cachexia. PMID- 1435018 TI - Harvey's account of his "discovery". PMID- 1435019 TI - "An exodus of enthusiasm": G. Alder Blumer, eugenics, and US psychiatry, 1890 1920. PMID- 1435020 TI - Smallpox inoculation and demographic trends in eighteenth-century Scotland. PMID- 1435021 TI - Extraordinary deaths of asylum inpatients during the 1914-1918 war. PMID- 1435022 TI - Choosing people: an aspect of the life of Lord Moran (1882-1977). PMID- 1435023 TI - Illustrations from the Wellcome Institute Library. The Moran papers. PMID- 1435024 TI - Dr John Radcliffe and his Trust. Essay review. PMID- 1435025 TI - [Step by step administrative education for physicians in Norway]. PMID- 1435026 TI - [HIV and ethics--information and disinformation]. PMID- 1435027 TI - [Conservative attitude is justified in septicemia after splenectomy]. PMID- 1435028 TI - [Do not keep investigations of suspected scientific fraud secret]. PMID- 1435029 TI - [Are the complaints caused by dental materials?]. PMID- 1435030 TI - [Amalgam problems are not of psychological origin]. PMID- 1435031 TI - [The motivation model--better utilization of time in alcohol detoxication]. PMID- 1435032 TI - [A better measure for exposure levels to tobacco smoke is needed]. PMID- 1435033 TI - [Consensus on treatment of atherosclerotic renal artery stenosis]. PMID- 1435034 TI - [The Solberga project--a new tool for spinal cord injuries]. PMID- 1435035 TI - [Intensified Scandinavian cooperation for better care in myasthenia gravis]. PMID- 1435036 TI - [Victims and perpetrators--abuse seen from the perspective of emergency care]. PMID- 1435037 TI - [Determination of methyl malonate--a new way for indication of cobalamin deficiency]. PMID- 1435038 TI - [Many mental disorders in adulthood have specific roots in childhood]. PMID- 1435039 TI - [1992--a year of international cooperation for cardiopulmonary resuscitation]. PMID- 1435040 TI - [Dissection of the internal carotid artery caused by energetic head turning during exercise]. PMID- 1435041 TI - [Experiences with the new law on involuntary commitment: cultural shock for the physicians and more demanding emergency service contra increased legal security and more distinct lines]. PMID- 1435042 TI - [The whole body is scrutinized]. PMID- 1435043 TI - [Equality, needs, freedom of choice and efficiency should be considered when priorities are made in an equitable health care]. PMID- 1435044 TI - [How to finance preventive care within the buy-sell system and house-physician organizations?]. PMID- 1435045 TI - [Improve information to scientists when their grant applications are refused]. PMID- 1435046 TI - [Difficult to evaluate quality in medical research]. PMID- 1435047 TI - [Estrogen popular again in prostatic cancer?]. PMID- 1435048 TI - [Are effects of continuous education of physicians measurable?]. PMID- 1435049 TI - [How to achieve changes within health care services?]. PMID- 1435050 TI - [The emotional capacity of humans--unexplored and unused possibility]. PMID- 1435051 TI - [Considerably reduced number of abortions among teenagers]. PMID- 1435052 TI - [Parenteral estrogen--a safe therapeutic alternative in prostatic cancer seen from the cardiovascular point of view?]. PMID- 1435053 TI - [The woman behind the syndrome. Dorothy Hansine Andersen. A pathologist and a pediatrician in New York with roots in Bornholm]. PMID- 1435054 TI - [Did the SBU report and the consensus conference clear the way for more restrictive preoperative investigation?]. PMID- 1435055 TI - [A minor birth injury with an unexpected late effect]. PMID- 1435056 TI - Spinally-mediated antinociception is induced in mice by an adenosine kinase-, but not by an adenosine deaminase-, inhibitor. AB - Relative involvement of adenosine deaminase and adenosine kinase in antinociception induced by endogenous adenosine was investigated. Antinociception induced by 5'-amino 5'-deoxyadenosine (5'-ADAdo; an adenosine kinase inhibitor) and deoxycoformycin (dCF; an adenosine deaminase inhibitor) administered i.t. was determined using the mouse tail-flick assay. Dose- and time-dependent antinociception was observed following i.t. administration of 5'-ADAdo, but not dCF. Antinociception induced by 5'-ADAdo was reversed by coadministration i.t. of theophylline, an adenosine receptor antagonist, in a dose-dependent manner. These data provide preliminary evidence that adenosine kinase plays a more significant physiological role than adenosine deaminase in the regulation of adenosine involved in spinally-mediated antinociception. PMID- 1435057 TI - Continuous light increases N-acetyltransferase activity in the optic lobe of the giant freshwater prawn Macrobrachium rosenbergii de Man (Crustacea: Decapoda). AB - Giant freshwater prawns, Macrobrachium rosenbergii de Man, were reared under three different lighting conditions: continuous darkness (DD), 12 hr of light and 12 hr of darkness (LD 12:12) and continuous light (LL). After one month, the prawns were sacrificed and optic lobes isolated from the eyestalks were determined for N-acetyltransferase (NAT) activities and melatonin concentrations. Gonads were weighed and examined under light microscopy. The optic lobes from LL prawns contained significantly higher activities of NAT than those from LD 12:12 prawns. The melatonin concentrations and size and histological features of the gonads from the three groups of prawns did not differ. The results indicate that continuous light increases NAT activities in the optic lobe of M. rosenbergii but has no drastic effect on gonadal growth. PMID- 1435058 TI - D2 dopamine receptor involvement in spinal dopamine-produced antinociception. AB - Experiments were performed on 79 lightly pentobarbital-anesthetized rats. Rats displayed a dose-dependent increase in tail-flick latencies following the injection of dopamine (DA) into the lumbar subarachnoid space through an intrathecal tube. Sulpiride, a D2-subtype receptor antagonist, antagonized the DA induced analgesia (antinociceptive) effect; while SCH-23390, a D1-subtype receptor antagonist, had no effect even in a higher dose. To further investigate whether the well-known spinal serotonergic, noradrenergic and opioidergic receptor systems were involved in DA-induced antinociception, their antagonists, methysergide, phentolamine, and naloxone were tested respectively. The results showed that phentolamine, but not methysergide or naloxone, could block the DA induced antinociception. The present data provide evidence that DA exerts antinociceptive effects through D2-subtype dopamine receptor(s) at the spinal level, and that spinal alpha-adrenergic receptors may mediate this effect. PMID- 1435059 TI - Urinary excretion of furosemide in rats with HgCl2-induced acute renal damage. AB - To examine the influence of mercuric chloride (HgCl2)-induced acute renal damage on urinary excretion of furosemide, HgCl2 (1 mg/kg) or its vehicle alone was given intraperitoneally to Wistar rats. The following two experiments were done. Study I: Three percent body weight (b.w.) of 1% NaCl solution or furosemide (30 mg/kg) in 3% b.w. of 1% NaCl solution was given orally before and after HgCl2 treatment, and an 8-hour urine was collected. Study II: Furosemide (30 mg/kg) was given orally, and blood samples were obtained at 1, 2, 3, 4, 6 and 8 hours after administration. Urinary excretion of N-acetyl-beta-D-glucosaminidase increased, and urine volume and urinary excretions of furosemide and sodium decreased in the HgCl2-treated rats. There were significant correlations between the urinary furosemide and its diuretic effects. Regression lines after HgCl2 were significantly different from those before treatment. The values of absorption as well as elimination rate constant were smaller, while the time to maximum concentration and the elimination half-life were longer in the HgCl2-treated rats compared to vehicle-treated animals. These results suggest that the urinary excretion of furosemide and the responsiveness of renal tubular cells to this agent are impaired in rats with HgCl2-induced acute renal damage. PMID- 1435060 TI - Detection of glucocorticoid-receptor complex oligomers in nuclear extracts from cells exposed to hormone at physiological temperature. AB - When HeLa cells were incubated with tritiated dexamethasone mesylate at 2 degrees C, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cytosolic and nuclear extracts revealed the presence of two monomeric receptor complex forms with estimated molecular masses of about 98 and 87 kDa. If cells were subjected to crosslinking with glutaraldehyde, a third form consisting of a 250 kDa oligomer was also detected. When HeLa cells were treated with dexamethasone mesylate at 37 degrees C, and were subjected to crosslinking, electrophoresis of cytosolic glucocorticoid-receptor complexes was drastically reduced, whereas their levels in nuclear extracts were not appreciably altered. PMID- 1435061 TI - The effects of metabolic stress on plasma progesterone in healthy volunteers and schizophrenic patients. AB - A number of preclinical studies suggest that progesterone may play an important role in the stress response, however, the effects of stress on progesterone in humans has not been established. Also, several lines of evidence indicate that schizophrenia may be associated with abnormal neurobiological responses to stress, but the effects of stress on progesterone in schizophrenia has not been investigated. The purpose of the present study was to examine the effects of stress on plasma progesterone and cortisol in healthy subjects and to determine if schizophrenic patients have altered stress-induced plasma progesterone levels compared to normal controls. Stress was induced through administration of 2 deoxyglucose (2DG), a glucose analog that impairs glucose metabolism resulting in a clinical state comparable to hypoglycemia. There were significant increases in plasma progesterone and cortisol levels following 2DG-induced glucoprivic stress in healthy controls. There was no relationship between stress related progesterone and cortisol elevations. Schizophrenic patients, in comparison to controls, had significantly greater 2DG-induced elevations in progesterone levels but no differences in stress-related cortisol levels. There was evidence that basal progesterone and cortisol levels were elevated in the schizophrenic patients. The implications of these data are discussed. PMID- 1435062 TI - Hypotensive activity of TCV-116, a newly developed angiotensin II receptor antagonist, in spontaneously hypertensive rats. AB - TCV-116, a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally (1 mg/kg per day) to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Blood pressure and plasma components of the renin angiotensin-aldosterone system were determined in these rats. TCV-116 produced a marked reduction in blood pressure without altering heart rate. Whereas plasma renin concentration (PRC), angiotensin I (Ang I) and angiotensin II (Ang II) all were significantly increased, plasma aldosterone was decreased by approximately 70% compared with control animals. These results not only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but support also the concept that the renin-angiotensin system plays an important role in the control of blood pressure in this animal model of human essential hypertension. PMID- 1435063 TI - Cardiovascular abnormalities associated with human and rodent obesity. AB - Obesity is a major risk factor for cardiovascular disease. However, a direct link between these two states is difficult to establish, since obesity frequently occurs with other disease states such as diabetes, hypertension and atherosclerosis. Clinical studies have clearly shown that uncorrected obesity is associated with cardiac hypertrophy and compromised ventricular function. A number of rodent models of obesity have been studied in terms of cardiovascular adaptations. Cardiac function of the obese Zucker rat appears to be normal at a younger age. Only after several months is depression in cardiac function discernable. These animals are mildly hypertensive, but do not exhibit the characteristic increase in cardiac output associated with human obesity. A unique characteristic of JCR:LA-cp rat is that they develop atherosclerotic and myocardial lesions. Hearts from these animals will maintain normal function when perfused with physiological levels of calcium. At higher calcium concentrations, however, mechanical function becomes impaired. Dietary-induced obese rats exhibit many of the hemodynamic alterations associated with human obesity, but there is no evidence to-date that these animals will develop severe cardiac depression. Short-term weight reduction apparently has beneficial cardiovascular effects, but weight cycling may be harmful. Given the widespread occurrence of obesity, further studies are warranted to characterize the cardiac manifestations of this condition. PMID- 1435064 TI - Effect of lysophosphatidylcholine on renal hemodynamics and excretory function in anesthetized rats. AB - The effect of myristoyl-lysophosphatidylcholine (myristoyl-LPC) on renal hemodynamics, electrolyte and water excretion was examined over a 90 min period in sodium pentobarbital anesthetized male Sprague Dawley rats. Intravenous infusion of myristoyl-LPC at 13 +/- 3 pmol/min resulted in a small fall in systemic blood pressure, a 13% decrease in renal plasma flow without significantly altering glomerular filtration rate and produced a slightly greater excretion of sodium and water than vehicle controls. These results suggest that short term myristoyl-LPC administration can significantly alter renal function producing a weak natriuresis and diuresis which is not dependent on systemic blood pressure and renal hemodynamic changes. PMID- 1435065 TI - Effect of a peptide leukotriene antagonist, ONO-1078 on antigen-induced airway microvascular leakage in actively sensitized guinea pigs. AB - We examined the effect of ONO-1078, a peptide leukotriene antagonist, on antigen induced airway microvascular leakage in ovalbumin-sensitized guinea pigs. When guinea pigs were pretreated with mepyramine, ovalbumin challenge increased vascular permeability to Evans blue dye in trachea, main bronchi and intrapulmonary airways. Oral administration of ONO-1078 significantly reduced microvascular leakage in intrapulmonary airways at doses more than 3 mg/kg, but not in trachea. Moreover, oral administration of ONO-1078 significantly reduced SRS-A mediated microvascular leakage into all airway tissues and was more effective in intrapulmonary airways at 3 mg/kg. Simultaneously, ONO-1078 also inhibited SRS-A mediated bronchoconstriction. On the other hand, azelastine (10 mg/kg, p.o.), an anti-asthma agent, failed to inhibit microvascular leakage into the airways. These results suggest that peptide leukotrienes may be important mediators of airway microvascular leakage, and that the inhibitory effect of ONO 1078 on antigen-induced airway microvascular leakage in addition to the blockade of bronchoconstriction may have therapeutic implications for bronchial asthma. PMID- 1435066 TI - Collagen biosynthesis in cultured rat testicular Sertoli and peritubular myoid cells. AB - The incorporation of 3H-proline into protein was regarded as a measure of total protein synthesis and the incorporation into hydroxyproline as indicative of collagen synthesis. Relative collagen synthesis (expressed as percent of total protein synthesized) by Sertoli and peritubular myoid cells cultured from 20-22 day old rat testis was estimated. In both secreted and cellular pools, relative collagen synthesis by Sertoli cells was significantly greater than by peritubular myoid cells. Coculture of Sertoli and myoid cells resulted in a significant increase in relative collagen synthesis when compared to monocultures of each cell type. Addition of serum to peritubular myoid cells resulted in a stronger stimulation of relative collagen production. Sertoli cell extracellular matrix inhibited relative collagen synthesis by peritubular myoid cells in the presence or absence of serum. Radioactivity into hydroxyproline as corrected per cellular DNA also showed similar results. Immunolocalization studies confirmed that both cell types synthesize type I and type IV collagens. These results indicate that stimulation of collagen synthesis observed in Sertoli-myoid cell cocultures is due to humoral interactions, rather than extracellular matrix, and Sertoli cell extracellular matrix regulates serum-induced increase in collagen synthesis by peritubular myoid cells. PMID- 1435067 TI - Caffeine potentiates the enhancement by choline of striatal acetylcholine release. AB - We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect. PMID- 1435069 TI - Transcriptional regulation of hexokinase I mRNA levels by TSH in cultured rat thyroid FRTL5 cells. AB - We investigated the effect of thyroid stimulating hormone (TSH) on the expression of hexokinase I mRNA by cultured rat thyroid FRTL5 cells. TSH stimulated hexokinase I gene expression in a time- and dose-dependent manner. An increase in hexokinase I mRNA was detected after 3 h of incubation with TSH, and a maximum was reached after 12 h showing about 2.5-fold increase at 1 mU/ml TSH. A nuclear run-on transcriptional assay showed that the effect of TSH on hexokinase I mRNA was due to an increase in the rate of gene transcription. (Bu)2cAMP and forskolin also increased hexokinase I mRNA expression to almost the same extent as TSH. These findings suggest that TSH stimulates hexokinase I gene expression at the transcriptional level via the cAMP-dependent pathway. PMID- 1435068 TI - A simple method for measurement of phosphoramidon-sensitive endothelin converting enzyme activity. AB - We have developed a rapid and convenient assay for measurement of the action of endothelin (ET) converting enzyme (ECE) using the scintillation proximity assay (SPA) principle. On incubation of [125I]big ET-1 at 37 degrees C for 0.5-6 hr with an enzyme preparation, the reaction was terminated by the addition of an ET 1-specific antibody formulated in a buffer designed to shift the pH to alkaline. The antibody was allowed to come to equilibrium for 1 hr at room temperature and the amount of ET-1 produced, detected in a single step by the addition of protein A SPA beads. Using this assay, ECE activities of enzyme preparations obtained from porcine cultured endothelial cells and rat lung were clearly detected. These activities were inhibited by phosphoramidon in a concentration-dependent manner. The SPA based assay is homogeneous requiring no separation steps and takes a half day to complete. This method is therefore suitable for the high throughput screening of potential ECE inhibitors. PMID- 1435070 TI - A simplified method for the determination of nitric oxide in biological solutions. AB - A new simplified procedure for determination of nitric oxide (NO) in biological solutions is described utilizing a new reducing system of nitric oxide prior to chemiluminescence. Advantages of the new method makes heating of the reducing solution unnecessary and avoids cooling and condensation of generated vapors. Only traces of acid with a high boiling point are used. The method permits analysis of small sample volumes (200 microL). The basal production of nitric oxide by freshly harvested endothelial cells ranged from 100 to 880 picomoles. PMID- 1435071 TI - Colloidal bismuth subcitrate and omeprazole inhibit alcohol dehydrogenase mediated acetaldehyde production by Helicobacter pylori. AB - We have recently shown that Helicobacter pylori possesses marked alcohol dehydrogenase (ADH) activity and is capable--when incubated with an ethanol containing solution in vitro--of producing large amounts of acetaldehyde. In the present study we report that some drugs commonly used for the eradication of H. pylori and for the treatment of gastroduodenal diseases are potent ADH inhibitors and, consequently, effectively prevent bacterial oxidation of ethanol to acetaldehyde. Colloidal bismuth subcitrate (CBS), already at a concentration of 0.01 mM, inhibited H. pylori ADH by 93% at 0.5 M ethanol and decreased oxidation of 22 mM ethanol to acetaldehyde to 82% of control. At concentrations above 5 mM, CBS almost totally inhibited acetaldehyde formation. Omeprazole, a drug also known to suppress growth of H. pylori, also inhibited H. pylori ADH and suppressed bacterial acetaldehyde formation significantly to 69% of control at a drug concentration of 0.1 mM. By contrast, the H2-receptor antagonists ranitidine and famotidine showed only modest effect on bacterial ADH and acetaldehyde production. We suggest that inhibition of bacterial ADH and a consequent suppression of acetaldehyde production from endogenous or exogenous ethanol may be a novel mechanism by which CBS and omeprazole exert their effect both on the growth of H. pylori as well as on H. pylori associated gastric injury. PMID- 1435072 TI - Pyridine and other coal tar constituents as inhibitors of potato polyphenol oxidase: a non-animal model for neurochemical studies. AB - Potato polyphenol oxidase activity was strongly and noncompetitively inhibited by the "Perov mixture" of coal tar components and by pyridine alone, while phenol competitively inhibited the enzyme. These two inhibitors are structural components of the parkinsonogenic neurotoxin N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP). By extension, dopamine and neuromelanin synthesis in the brain may be influenced by the inhibitory effects of such compounds upon the copper-dependent steps of tyrosine metabolism. The non-animal model used in this study may represent an alternative to the use of animal tissues in neurodegenerative disease research. PMID- 1435073 TI - Non-selectivity of new bradykinin antagonists for B1 receptors. PMID- 1435074 TI - Potassium permeability of fetal rat pancreatic islets: abnormal sensitivity to glucose. AB - Potassium channels of fetal rat islets have been recently reported to be inadequately regulated by stimulation with glucose when compared to islets of adult rats. Though in patch clamp experiments the properties of their KATP channels were shown to be comparable to those from adult rats, until now no closure could be demonstrated with the technique measuring the 86Rb+ efflux. Using this technique, in the presence of a basal (3 mM) glucose concentration the 86Rb+ efflux was completely insensitive to a stimulation with glucose (5.6 mM) or tolbutamide. In contrast, in islets perifused in the absence of glucose the introduction of a low glucose concentration (3 mM) or stimulation with tolbutamide alone inhibited the 86Rb+ efflux, confirming the presence of functioning KATP-channels. The absolute value of the 86Rb+ efflux rate in the absence of glucose was, however, much lower in fetal rat islets as normally observed in adult rat islets. Apart from this, the ATP content of fetal rat islets remained unchanged at either glucose concentration tested. It is suggested that in islets of fetal rats a K+ permeability is present and can be inhibited by glucose and tolbutamide but in contrast to islets of adult rats the K+ efflux is already maximally inhibited in the presence of 3 mM glucose. This may be one reason why pancreatic islets of fetal rats do not respond to glucose-stimulation with an adequate calcium uptake and insulin release. PMID- 1435075 TI - Transfer of 3H-gossypol to neonatal rats via milk of nursing dams. AB - Gossypol is a naturally occurring toxin with potent antifertility action in both males and females. Transfer of gossypol via milk from lactating mother to neonates has not been documented. One theory for the lack of such a finding is that gossypol, once tightly bound to milk proteins, is not extractable by conventional extraction methods for HPLC analysis. This study was designed to examine the possibility and dynamics of transmammary transfer of radioactively labelled gossypol to neonates through nursing. Nursing rats were dosed with fifty microCi of 3H-gossypol in 0.5 ml of dimethyl sulfoxide via oral intubation on Day 10 post-partum. Six hours after treatment, significant amounts of 3H-gossypol were detected in the coagulated milk collected from the stomachs of the neonates as well as in the blood, liver, lung, spleen and a number of other tissues of these pups. While most neonatal tissues showed a steady decline in 3H-gossypol retention over time regardless of neonatal gender, adrenal glands and gonads preferentially accumulated 3H-gossypol in a time- and sex-dependent manner during the 24-hour sampling period. The results demonstrate that 3H-gossypol is transferred via milk from the nursing dams to their neonates. Thus, the gossypol content of milk presents a conceivable threat to neonatal health, especially to the normal function of steroidogenic organs. PMID- 1435076 TI - Pulmonary biotransformation of insulin in rat and rabbit. AB - In vitro biodegradation of insulin in rabbit and rat lung homogenates was investigated. Insulin can be sequentially metabolized into two primary fragments in rabbit lung homogenate by an aminopeptidase. The amino acid sequences of the fragments were found to be the des-Phe-InsulinB1 (Metabolite I) and des-Phe-Val InsulinB1-2 (Metabolite II). However, only the former metabolite (Metabolite I) was identified in the rat lung homogenate. The km and Vm values associated with rabbit lung homogenate were 0.29 +/- 0.14 mM and 16.4 +/- 6.9 microM/hr/mg protein, respectively, whereas those for a rabbit lung preparation containing both microsomes and cytosol were 0.22 +/- 0.07 mM and 17.9 +/- 5.4 microM/hr/mg protein, respectively. The km and Vm associated with the cytosolic fraction of rabbit lung were 0.32 +/- 0.16 and 20.6 +/- 6.1 microM/hr/mg protein, respectively. The results indicate that the lung aminopeptidase may be a cytosolic enzyme. The degradation of dimeric insulin in the lung homogenate was faster than that of hexameric insulin due to the difference in collision frequency between the enzyme and insulin aggregates. The major metabolites in the lungs reportedly retain almost the same bioactivity of insulin, suggesting that the pulmonary route of insulin delivery will not adversely affect its hypoglycemic activity. PMID- 1435077 TI - Adaptation in synergistic muscles to soleus and plantaris muscle removal in the rat hindlimb. AB - Although the soleus muscle comprises only 6% of the ankle plantar flexor mass in the rat, a major role in stance and walking has been ascribed to it. The purpose of this study was to determine if removal of the soleus muscle would result in adaptations in the remaining gastrocnemius and plantaris muscles due to the new demands for force production imposed on them during stance or walking. A second purpose was to determine whether the mass or the fiber type of the muscle(s) removed was a more important determinant of compensatory adaptations. Male Sprague-Dawley rats underwent bilateral removal of soleus muscle, plantaris muscle, or both muscles. For comparison, compensatory hypertrophy was induced in soleus and plantaris muscles by gastrocnemius muscle ablation. After forty days, synergist muscles remaining intact were removed. Mass, and oxidative, glycolytic, and contractile enzyme activities were determined. Despite its role in stance and slow walking, removal of the soleus muscle did not elicit a measurable alteration in muscle mass, or in citrate synthase, lactate dehydrogenase, or myofibrillar ATPase activity in gastrocnemius or plantaris muscles. Similarly, removal of the plantaris muscle, or soleus and plantaris muscles, had no effect on the gastrocnemius muscle, suggesting that this muscle was able to easily meet the new demands placed on it. These results suggest that amount of muscle mass removed, rather than fiber type, is the most important stimulus for compensatory hypertrophy. They also suggest that slow-twitch motor units in the gastrocnemius muscle play an important role during stance and locomotion in the intact animal. PMID- 1435078 TI - Muscarinic and nicotinic activities of the novel acetylcholine analog acetylselenonium choline. AB - The present paper further characterizes the cholinergic properties of acetylselenonium choline (ASeCh, (CH3)2Se+CH2CH2OCOCH3). The data demonstrate that ASeCh possesses muscarinic receptor agonist properties as evidenced by vasodepressor and smooth muscle contractile activities which are enhanced by physostigmine and antagonized by atropine. ASeCh also possessed nicotinic agonist activity on frog rectus abdominis tissue which was potentiated by physostigmine, and blocked by d-tubocurarine. The relative potencies of ASeCh ranged from approximately 1% to approximately 6% of the potency of acetylcholine in the three types of preparations examined. PMID- 1435079 TI - Synthesis and release of acetylcholine in the rabbit kidney cortex. AB - Several cholinergic processes were demonstrated and partially characterized in rabbit kidney cortical minces: choline uptake, acetylcholine synthesis and calcium-dependent release. Minces took up labelled choline, acetylated it, and stored it in a pool that was not readily accessible to physostigmine-sensitive cholinesterase activity. [3H]Acetylcholine synthesis but not [3H]choline uptake was inhibited by the removal of sodium ions or incubation at 0 degrees C. The release of newly synthesized [3H]acetylcholine was increased by 300 mOsmol urea in a calcium-dependent manner, but not by potassium depolarization (300 mOsmol), vasopressin (10 microM), or bradykinin (10 microM). These results suggest that acetylcholine may be synthesized by non-neuronal rabbit kidney cortical cells and that this transmitter may be released in response to physiological levels of urea. PMID- 1435080 TI - Ontogeny of endothelin and its receptors in rat brain. AB - The ontogeny of endothelin (ET) system in rats was studied in preterm (18 days of gestation), term (21 days of gestation) and 1 week post term rats. Brains were dissected out and (1) processed for the estimation of endogenous ET-1 by RIA and (2) membranes were prepared for radioreceptor binding. Receptor characteristics, affinity (Kd) and density (Bmax) were determined using [125I] ET-1 and [125I] SRT 6b (which is structurally similar to ET) and cold ET-1 or SRT 6b as displacer. ET levels were found to be 25.66 +/- 3.18 pg/g protein in preterm, 47.37 +/- 5.31 pg/g protein in term and 48.30 +/- 1.90 pg/g protein in post term rats. ET levels were significantly lower in preterm as compared to term and post term rats. Preterm, term and post term rats showed single high affinity binding site for both [125I] ET-1 and [125I] SRT 6b. The Kd values for [125I] ET-1 and [125I] SRT 6b binding were similar in preterm, term and post term rats. The Bmax values of both [125I] ET-1 and [125I] SRT 6b binding were found to be similar in preterm and term rats while they were significantly higher in post term rats. In adult (4 month old) rats the Kd values were similar to neonatal rats while the Bmax values were significantly lower than the post term neonatal rats. It is concluded that ET and its receptors are developmentally regulated and there is a possibility that endogenous ET is involved in the regulation of ET receptor density. PMID- 1435081 TI - Inhibition of lymphocyte proliferation by liver arginase. AB - The activities of thymidine kinase and uridine kinase (enzymes for pyrimidine salvage pathway) in phytohemagglutinin (PHA)--prestimulated lymphocytes were inhibited by arginase in a similar pattern to the inhibition on thymidine incorporation. Further study revealed that arginase did not directly affect the activities of these enzymes in the cell-free system. Thymidine kinase and uridine kinase activities of PHA-prestimulated lymphocytes were inhibited by arginase making their activities as low as that cultured in arginine-free RPMI-1640 medium. These results suggest that arginine-depletion in the culture medium is the primary mode of action of arginase on the inhibition of mitogen-stimulated lymphocyte proliferation. PMID- 1435082 TI - The presence of cocaine and benzoylecgonine in rat cerebrospinal fluid after the intravenous administration of cocaine. AB - Cocaine hydrochloride, in doses of 0.5, 1.0, 2.0 and 4.0 mg/kg, iv, was administered to male Sprague-Dawley rats. Cerebrospinal fluid (CSF) was collected from the cisterna magna over a 20 min period and blood samples were obtained at 20 min after cocaine administration. In addition, blood samples for the 1 mg/kg dose of cocaine were collected at 2, 10, 20 and 30 min following drug injection. Gas chromatography/mass spectrometry was used for the analysis of cocaine and its metabolites in plasma and CSF. The disappearance of cocaine (1 mg/kg) from the plasma exhibited first order kinetics with a half-life of 18.11 +/- 3.22 min. Cocaine and benzoylecgonine were found in CSF and the concentrations of cocaine and benzoylecgonine increased in CSF as the doses of cocaine were increased. CSF flow rates were not altered by the iv administration of cocaine or benzoylecgonine. The CSF-to-plasma ratios for cocaine were quite similar to each other over the dosage range of cocaine that was administered; however, the CSF-to plasma ratios for benzoylecgonine decreased as the concentrations of benzoylecgonine increased in plasma and CSF. When benzoylecgonine (2 mg/kg, iv) was given, the compound was detected in CSF indicating that benzoylecgonine can enter into the central nervous system from the peripheral blood. This investigation shows that cocaine and benzoylecgonine can be assayed in CSF and that the plasma levels of these compounds correlate with their concentrations in CSF. PMID- 1435083 TI - The protection against gentamicin nephrotoxicity in the streptozotocin-induced diabetic rat is not related to gender. AB - Since gender can influence the renal toxicity of a drug in a given species, the present study was undertaken to evaluate the role of sex in the protection against gentamicin (G)-induced nephrotoxicity afforded by diabetes mellitus (DM) in the rat. We have compared the effects of administration of G (40 mg/kg/day, for 14 days) on male and female DM Sprague-Dawley rats. Non-diabetic animals of both sexes receiving identical doses of G served as controls. At the end of the experiment on day 14, both female (F) and male (M) control groups had similar and marked evidence of nephrotoxicity: elevation of plasma creatinine (F 1.7 +/- 0.7; M 2.8 +/- 0.6 mg/dl), decrease in endogenous 24-h creatinine clearance (Ccr) (F0.3 +/- 0.1; M 0.2 +/- 0.1 ml/min/100 g BW), and histological evidence of severe acute tubular necrosis. In marked contrast, the DM rats showed no functional or morphological evidence of renal damage throughout the study regardless of their gender (day 14: plasma creatinine: F 0.2 +/- 0.03; M 0.2 +/- 0.02; Ccr: F 1.2 +/- 0.1; M 1.6 +/- 0.1 ml/min/100 g BW), and they also accumulated less G in their kidney cortex than the C rats. The male controls exhibited higher renal cortex accumulation of G than the female controls (p < 0.05), whereas the opposite occurred in the DM groups (p < 0.01). Because the validity of using Ccr for the evaluation of GFR changes in experimental nephrotoxicity has been questioned, we have compared, in a separate experiment, three different methods of estimation of GFR (simultaneous short clearances of inulin and Ccr, and 24-h Ccr) in conscious female Sprague-Dawley rats undergoing the same treatment with G described above. At no time during the study did the method used for estimation of the GFR influence the results. We conclude that male and female Sprague-Dawley rats with diabetes are functionally and morphologically equally protected against G. Furthermore, no gender-related differences in the magnitude of G-induced nephrotoxicity was demonstrated in the non-diabetic control animals. PMID- 1435084 TI - Repeated corticosterone treatment attenuates behavioural and neuroendocrine responses to 8-hydroxy-2-(di-n-propylamino) tetralin in rats. AB - The effects of 5 day corticosterone treatment (50 mg/kg s.c.; 2 x daily) are investigated on the behavioural and neuroendocrine responses to a 5-HT-1A selective agonist, 8-hydroxy -2-(di-n-propylamino) tetralin (8-OH-DPAT) in rats. Daily corticosterone treatment decreased body weight and food intake. After 5 day treatment a drug challenge of 0.25 and 0.5 mg/kg 8-OH-DPAT given on the sixth day produced smaller forepaw treading but comparable head waeving, flat body posture and also hypothermia in 5 day corticosterone than 5 day saline injected rats. Hyperphagic effects of only 0.25 mg/kg 8-OH-DPAT were attenuated in 5 day corticosterone injected animals. The effects of 8-OH-DPAT on the increases of plasma corticosterone were markedly attenuated in the 5 day corticosterone injected animals. The findings may help towards an understanding of steroid induced affective changes and psychosis. PMID- 1435085 TI - Treatment parameters of desensitization to capsaicin. AB - Desensitization of sensory afferents with topical capsaicin has been employed to treat a variety of neuropathic disorders in humans, however, few studies have been undertaken to systematically evaluate treatment parameters to determine the optimal dose and frequency of treatment needed to achieve and maintain desensitization. The effects of several treatment parameters, including dose, number of exposures, interval between exposures and duration of exposure, on the development, magnitude and duration of desensitization following local treatment with capsaicin and related compounds are described. PMID- 1435086 TI - Therapeutic potential of capsaicin-like molecules: studies in animals and humans. AB - Capsaicin-sensitive primary afferent neurons in the peripheral nervous system are widely distributed to both the somatic and visceral territories: their inactivation following capsaicin "desensitization" is expected to produce analgesia and to be useful for a number of human diseases such as asthma, urinary incontinence, inflammatory diseases of the gut, arthritis and psoriasis. The present communication reviews the therapeutic potential of capsaicin-like drugs in the pathophysiology of the mammalian urinary bladder. PMID- 1435087 TI - Stimulation of myenteric plexus neurite outgrowth by insulin and insulin-like growth factors I and II. AB - A defined culture medium containing insulin, insulin-like growth factor I (IGF-I) or insulin-like growth factor II (IGF-II) supported morphological development of myenteric plexus neurons derived from neonatal guinea pigs. Insulin increased neurite outgrowth 3-fold at concentrations as low as 0.2 nM. Similar significant and dose-dependent increases in neurite outgrowth were noted with IGF-I and IGF II. Stimulation of neurite outgrowth was abolished by exposure to cytosine arabinofuranoside, an agent toxic to non-neuronal cells, implying that trophic effects of insulin or insulin-like growth factors require the presence of non neuronal elements in culture. PMID- 1435088 TI - Interleukin-1 inhibits serotonin release from the hypothalamus in vitro. AB - During a 60-min incubation period, the in vitro release of serotonin (5-HT) from the hypothalami of control male rats decreased by 12.3 +/- 3.1%. In contrast, the presence of 25 ng of interleukin-1 beta (IL-1 beta) in the incubation medium more than doubled this decrease to 29.3 +/- 3.3% (P < 0.001), and the presence of 50 ng of IL-1 beta more than quadrupled this decrease to 53.7 +/- 7.4% (P < 0.001). The decrease produced by the higher dose of IL-1 beta was significantly greater than that produced by the lower dose (P < 0.01), indicating a dose response. During the next two 60-min periods when the hypothalami of the control as well as treatment groups were incubated without IL-beta, 5-HT release continued to decrease and then became stabilized in the control group. In contrast, 5-HT release in the treatment groups rebounded before becoming stabilized at levels that were not significantly different from those in the control group. It is concluded that IL-1 beta inhibits the release of serotonin from the hypothalamus in vitro. PMID- 1435089 TI - Influence of renal denervation on chronopharmacology of furosemide in rats. AB - Our previous studies have suggested that the adrenergic nervous system is involved in the mechanism responsible for the time-dependent change in the urinary excretion of furosemide in rats. To examine a potential role of renal nerves in this phenomenon, renal denervation or sham operation was performed using unilaterally nephrectomized rats. Furosemide (30 mg/kg) was given orally at 12 am or 12 pm. Urine was collected for 8 hours after furosemide dosing, and urinary excretions of furosemide and sodium were determined. Urinary furosemide excretion and diuretic effects of the agent (urine volume and urinary sodium) were significantly greater at 12 am than at 12 pm in the sham-operated group of rats. However these administration time-dependent changes in urinary furosemide and its diuretic effects disappeared in the renal-denervated group of animals. These results suggest that the renal nerves contribute to the time-dependent changes in the urinary excretion of furosemide and its subsequent diuretic effects. PMID- 1435090 TI - Centrally acting endogenous hypotensive substances in rats subjected to endotoxic shock. AB - Cerebroventricular perfusate (CVP) from rats subjected to endotoxic shock was infused into the lateral ventricle of the naive rat. This procedure produced a hypotensive response in the recipient rat which could be reversed by the intravenous injection of the opioid antagonist naltrexone. The degree of endotoxemic hypotension in the donor rat was attenuated by perfusing the cerebroventricular system with mock CSF. The results suggest the existence of endogenous hypotensive substances in rat central nervous system, possibly opioid in nature, which may play a critical role in the pathogenesis of endotoxic shock. PMID- 1435091 TI - The accumulation and disappearance of cocaine and benzoylecgonine in rat hair following prolonged administration of cocaine. AB - Hair samples were obtained at various time periods from male Sprague-Dawley rats following the injection of cocaine hydrochloride in doses of 5, 10, and 20 mg/kg, ip, for 28 days. Hair samples were also taken continually after the dosing was stopped until the presence of cocaine and benzoylecgonine were no longer detected in hair. Cocaine and benzoylecgonine in hair and plasma were analyzed by gas chromatography/mass spectrometry. Both cocaine and benzoylecgonine were found in hair samples 4 days after the initiation of cocaine administration. When cocaine dosing was stopped after 28 days, approximately 25 to 30 days were required for cocaine and benzoylecgonine to disappear from rat hair in the group of animals that received the highest dose of cocaine. The disappearance of cocaine and benzoylecgonine followed first-order kinetics. The mean rate constant and mean half-life for cocaine disappearance from hair were 0.212 +/- 0.005 day-1 and 3.31 +/- 0.09 days, respectively, and the mean rate constant and mean half-life for benzoylecgonine disappearance from hair were 0.098 +/- 0.006 day-1 and 6.90 +/- 0.28 days, respectively. The mean plasma concentrations of cocaine on Day 25 for the 5, 10, and 20 mg/kg doses of cocaine were 508 +/- 42, 852 +/- 95, and 2027 +/ 75 ng/mL, respectively, and the mean plasma benzoylecgonine levels for the 5, 10, and 20 mg/kg doses of cocaine were 49.9 +/- 7.0, 103.3 +/- 9.3, and 191.0 +/- 16.0 ng/mL, respectively. There was a positive correlation between the doses of cocaine hydrochloride administered and the plasma levels of both cocaine and benzoylecgonine. This study showed that cocaine and benzoylecgonine can be measured in rat hair following the administration of cocaine and that it was possible to correlate the concentrations of cocaine and benzoylecgonine found in hair with the doses of cocaine that were administered. PMID- 1435093 TI - Effects of dietary linseed oil and marine oil on lipid peroxidation in monkey liver in vivo and in vitro. AB - Diets rich in linoleic acid (CO) from corn oil, or in linoleic acid and either alpha-linolenic acid (LO) based on linseed oil or n-3 fatty acids (MO) from menhaden oil were fed to male and female Cynomolgus monkeys for 15 wk. In the liver a 40% reduction of alpha-tocopherol occurred in the MO group relative to the CO and LO groups followed by increased formation of lipofuscin in vivo. A four-fold increase of alpha-tocopherol in the MO diet (MO + E) brought the level in the liver to that found with CO and LO. The increased peroxidation in the MO group in the liver phospholipids was associated with the replacement of 60% of the n-6 fatty acids by n-3 fatty acids from menhaden oil. Similar fatty acid profiles were found in groups fed MO and MO + E, respectively. Compared to the CO fed group, feeding alpha-linolenic acid only resulted in a slight incorporation of n-3 fatty acids in the liver membranes mainly due to a direct incorporation of alpha-linolenic acid. However, in monkeys fed menhaden oil more than 30% of the total fatty acids in the liver phospholipids were n-3 fatty acids. The various diets did not influence the activity of liver catalase (EC 1.11.1.6) nor superoxide dismutase (EC 1.15.1.1), but glutathione-peroxidase activity (EC 1.11.1.9) was higher in monkeys fed the MO diet. The catalase activity in females was 20% higher than in males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435092 TI - Comparison of the effect of the amount and degree of unsaturation of dietary fat on plasma low density lipoproteins in vervet monkeys. AB - The effects of the degree of unsaturation and of the amount of dietary fat on low density lipoprotein (LDL) concentration and composition were determined in vervet monkeys. Diets with fat contents of 41, 31 and 18% energy, each with a low and a high polyunsaturated to saturated fatty acid ratio (P/S; 0.27-0.38 and 1.13-1.47) were fed to six female vervet monkeys for two months. Another six females were given a low fat, high P/S diet for the same period of time, to serve as a reference. The cholesterol contents of the diets were low (21-33 mg per day) and relatively constant. LDL cholesterol concentrations decreased significantly (P < or = 0.01) when the dietary fat content decreased from 31 to 18% of energy. The dietary P/S ratio only affected LDL cholesterol concentrations during moderate (31% of energy) fat intake, where LDL cholesterol increased (P < or = 0.01) with a decrease in dietary P/S. Substantial individual variations were observed in LDL cholesterol concentration responses to dietary fat changes. The changes in LDL cholesterol concentrations were the result of changes in the concentration of LDL particles, as the molecular composition did not differ significantly between dietary periods. The high density lipoprotein cholesterol and the plasma triacylglycerol concentrations were not influenced by the dietary fat changes. During the high P/S diets, the percentage of 18:2 (linoleic acid) increased (P < or = 0.01) and that of 18:1 (oleic acid) decreased (P < or = 0.01) in LDL esterified cholesterol, as compared to the low P/S diets. In adipose tissue triacylglycerol the percentage of 18:2 was three times higher (P < or = 0.01) during the high P/S diets than during the low P/S diets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435094 TI - The effect of a histidine-excess diet on cholesterol synthesis and degradation in rats. AB - Feeding a diet high in excess histidine (5% L-histidine) resulted in hypercholesterolemia and enlargement of the liver in rats. To clarify the mechanism of the hypercholesterolemia, cholesterol synthesis and degradation were followed. We found that hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in histidine-excess diet rats was significantly higher than in rats fed a basal diet. Incorporation of [3H] water into cholesterol of liver slices from rats fed the histidine-excess diet was higher than incorporation into liver slices from rats fed the basal diet (expressed per liver per 100 g body weight). In vivo incorporation of [3H] water into hepatic cholesterol was also higher, but the incorporation into cholesterol of the small intestine was lower in histidine fed rats than in rats fed the basal diet (expressed per liver per 100 g body weight). Hepatic cholesterol 7 alpha-hydroxylase activity was similar in both groups. The data suggest that the hypercholesterolemia caused by histidine-excess diet appears to be due to the stimulation of cholesterol synthesis in the liver. PMID- 1435095 TI - trans fatty acids. 5. Fatty acid composition of lipids of the brain and other organs in suckling piglets. AB - The effects of dietary trans fatty acids on the fatty acid composition of the brain in comparison with other organs were studied in 3-wk-old suckling piglets. In Experiment (Expt.) 1 the piglets were delivered from sows fed partially hydrogenated fish oil (PHFO) (28% trans), partially hydrogenated soybean oil (PHSBO) (36% trans) or lard (0% trans). In Expt. 2 the piglets were delivered from sows fed PHFO, hydrogenated fish oil (HFO) (19% trans) or coconut fat (CF) (0% trans) with two levels of dietary linoleic acid (1 and 2.7%) according to factorial design. In both experiments the mother's milk was the piglets' only food. The level of incorporation of trans fatty acids in the organs was dependent on the levels in the diets and independent of fat source (i.e., PHSBO, PHFO or HFO). Incorporation of trans fatty acids into brain PE (phosphatidylethanolamine) was non-detectable in Expt. 1. In Expt. 2, small amounts (less than 0.5%) of 18:1 trans isomers were found in the brain, the level being slightly more on the lower level of dietary linoleic acid compared to the higher. In the other organs the percentage of 18:1 trans increased in the following order: heart PE, liver mitochondria PE, plasma lipids and subcutaneous adipose tissue. Small amounts of 20:1 trans were found in adipose tissue and plasma lipids. Other very long-chain fatty acids from PHFO or HFO (i.e., 20:1 cis and 22:1 cis + trans) were found in all organ lipids except for brain PE. Dietary trans fatty acids increased the percentage of 22:5n-6 in brain PE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435096 TI - Lipids in cancer: an introduction. PMID- 1435097 TI - Dietary fat and breast cancer. AB - High-fat diets are thought to increase the risk of breast cancer because animals develop mammary cancer more readily when they are fed high-fat compared to low fat diets, and breast cancer incidence and mortality are higher in countries with high-fat as compared to those with low-fat diets. Prospective cohort studies and case-control studies have failed to provide much support for this theory, but such studies are less capable of showing the relationship because of smaller differences in dietary fat intakes of the study populations; difficulties in assessing the diets of individuals over a period of time; and possible differences in genetic susceptibility of cases and controls to breast cancer. Studies on migrants have shown that breast cancer incidence and mortality increase in populations who move from countries with low-fat to those with high fat diets, indicating that observed geographical differences in breast cancer are due to environmental rather than genetic factors. This is supported by time-trend studies showing that breast cancer increases in countries as the level of fat in the diet rises. Controlled, long-term dietary trials are needed to determine whether the converse is true: namely, that reduction of dietary fat can reduce the risk of breast cancer. Large groups are required to achieve statistical significance, but smaller numbers may be adequate for studies on high-risk individuals. Preliminary experiments already have demonstrated the feasibility of carrying out such dietary trials. PMID- 1435099 TI - Dietary fat and the development of pancreatic cancer. AB - Pancreatic cancer is the fifth most common cause of death due to cancer. Except for an association with cigarette smoking, its etiology is poorly understood. Because of the dearth of epidemiological clues as to causation, studies with experimental animal models assume greater importance. Rodent models of pancreatic cancer indicate that while dietary fat per se does not cause pancreatic cancer, it does enhance or promote tumor development. Subsequent to treatment with a pancreatic carcinogen, high intakes of dietary unsaturated fats of the n-6 series, but not saturated fats, enhance or promote tumor development. A requisite level of linoleic acid is needed for this promotion. Fats of the n-3 series (e.g., certain fish oils) are inhibitory to tumor growth. Promotion by dietary fats appears only partly related to the high caloric content of fat. Mechanistically, certain dietary unsaturated fats appear to selectively enhance the growth rate of carcinogen-induced, pre-cancerous lesions. Irrespective of precise understanding of mechanisms of promotion, it appears possible to intervene in the process of cancer development and reduce the burden of cancer. Experimentally, this may be accomplished by decreasing total fat intake, decreasing caloric intake, increasing exercise or increasing the intake of n-3 fatty acids. PMID- 1435098 TI - Dietary fat, fatty acids and prostate cancer. AB - International comparisons suggest a relationship between prostate cancer incidence and dietary fat, an inference supported by migration studies, the changing incidence rates and levels of animal fat consumption in Japan and the results from some case-control studies. Overall, however, epidemiological studies have been inconclusive, and although prostate cancer is one of the hormone dependent tumors, evidence of interactions between dietary fats and male endocrine function is incomplete. Laboratory experimentation has shown that n-6 fatty acids stimulate and n-3 fatty acids inhibit human prostate cancer cells in culture; also, feeding diets rich in marine oils suppresses growth of these cells as solid tumors in athymic nude mice. These growth effects of polyunsaturated fatty acids appear to involve both prostaglandins and leukotrienes and to interconnect with autocrine regulation by epidermal growth factor-related polypeptides. PMID- 1435100 TI - Dietary fat and colon cancer: animal model studies. AB - Since it was first suggested that high dietary fat is a risk factor in colon cancer, there have been several studies to test this hypothesis. Epidemiologic studies suggested a positive association between dietary fat and colon cancer. Laboratory animal model studies demonstrated that not only the amount of fat, but also types of fat differing in fatty acid composition are important determining factors in colon tumor development. Chemically-induced colon tumor incidence was increased in rats fed the semipurified diets containing 23% corn oil, safflower oil, lard or beef tallow (high-fat) as compared to those fed 5% corn oil, safflower oil, lard or beef tallow diets (low-fat). Diets containing 23% coconut oil, olive oil or fish oil, or high-fat diets containing varying levels of trans fat, had no colon tumor-enhancing effect compared to their respective low fat diets. The stage at which the effect of dietary fat is exerted appears to be mostly during the post-initiation phase of colon carcinogenesis. Lack of a colon tumor enhancing effect of dietary fish oil is observed both during the initiation and postinitiation phases. The mechanisms by which various dietary fats increase colon carcinogenesis are not fully understood. In most instances, however, the high-fat diet appears to enhance tumorigenesis through elevation of agents, such as secondary bile acids, that act as promoters of tumor development. Lack of colon tumor promotion by dietary fish oil and trans fat appears to be mediated through their effect on mucosal ornithine decarboxylase activity, colonic secondary bile acids and/or prostaglandin synthesis. PMID- 1435101 TI - Humans, lipids and evolution. AB - The genetically ordered physiology of contemporary humans was selected over eons of evolutionary experience for a nutritional pattern affording much less fat, particularly less saturated fat. Current dietary recommendations do not accord exactly with those generated by an understanding of prior hominoid/hominid evolution. Similarly, widely advocated standards for serum cholesterol values fail to match those observed in recently studied hunter-gatherers, whose experience represents the closest living approximation of "natural" human lipid metabolism. The evolutionary paradigm suggests that fats should comprise 20-25% of total energy intake, that the ratio of polyunsaturated to saturated fat should exceed 1.0, and that total serum cholesterol levels should be below 150 mg/dL (approximately 4 mM/L). PMID- 1435103 TI - Medicine and Law. Index 1982-1991. PMID- 1435104 TI - Neuroendocrine challenge tests: assessment of 5-HT function in anxiety and depression. PMID- 1435102 TI - Dietary fat and breast cancer risk: the feasibility of a clinical trial of breast cancer prevention. AB - Animal experimental evidence and human ecological data suggest that dietary fat intake is related to breast cancer risk. Epidemiological studies within countries have given inconsistent results but are limited by the restricted range of dietary intake found in Western populations and by error in the measurement of fat consumption. Experimental evidence, derived from controlled clinical trials in which the range of fat intake is increased beyond that seen in most Western populations, is capable of overcoming this limitation of observational epidemiology, and would provide the strongest evidence available concerning the relationship of dietary fat intake to breast cancer risk. Further, such trials are the only means likely to answer the question of whether breast cancer risk in high-risk subjects can be modified by changing dietary fat intake. We describe here several aspects of the feasibility of an experimental approach to this problem, including the identification of subjects at increased risk for breast cancer, and the demonstration that such subjects will enter a clinical trial of dietary fat reduction and comply with a low-fat diet. It is shown that subjects can be recruited and retained in such trials, that satisfactory dietary compliance can be achieved over at least 24 mon and that the subjects selected are at demonstrably increased risk of breast cancer. This finding indicates that it is feasible to test the dietary fat-breast cancer hypothesis experimentally by means of a clinical trial. PMID- 1435105 TI - The tyramine conjugation test as a trait marker for endogenous unipolar depression and a predictor of treatment response. PMID- 1435106 TI - John Archer, M.B.: one of the great medical pioneers of this state. PMID- 1435107 TI - On deaning and Hopkins: an interview with Richard S. Ross, M.D., dean emeritus of the Johns Hopkins University School of Medicine. Interview by Janet Farrar Worthington. PMID- 1435108 TI - Papillary muscle rupture: a reversible cause of cardiogenic shock. PMID- 1435109 TI - Instrumental musicians showing technique impairment with painful overuse. PMID- 1435110 TI - Medical peer review, litigation, and the exercise of judgment. PMID- 1435111 TI - Selected communicable diseases in Maryland. October, 1992. PMID- 1435112 TI - Imaging case of the month. Neurosarcoidosis. PMID- 1435113 TI - Motor-sensory neuropathy. PMID- 1435114 TI - Nonnursing functions: put the problem in writing. PMID- 1435115 TI - Lamaze technique for pediatric pain. PMID- 1435116 TI - Tracheostomy care: preparing parents for discharge. PMID- 1435117 TI - EPSDT: The lawsuit. PMID- 1435119 TI - A ritual of remembrance. PMID- 1435120 TI - Pathophysiology and nursing management of persistent pulmonary hypertension of the newborn. PMID- 1435121 TI - Exploratory data analysis. Part I: Skepticism and openness. PMID- 1435118 TI - Critical care for the maternity patient. PMID- 1435122 TI - Preventing hepatitis B in infants. PMID- 1435123 TI - Presidential address: 'I am in blood...' (Macbeth act III scene IV). PMID- 1435124 TI - Trends in suicide (1983-1987). AB - From over 20,000 autopsies performed by the Department of Forensic Medicine of The London Hospital Medical College over a period of 5 years from 1983 to 1987, 7.4 per cent were classified as unnatural deaths, and from these 659 (3.2 per cent) were suicides. The object of this paper is to study the different methods of self-destruction, the incidence of these methods by sex and age, and evidence left by the deceased. PMID- 1435125 TI - Poppy seeds: implications of consumption. AB - Three white poppy seed samples of Papaver somniferum L were found to contain total morphine (free and bound) in the range 58.4 to 62.2 micrograms/g seeds and total codeine (free and bound) in the range 28.4 to 54.1 micrograms/g seeds. Soaking seeds in water was found to remove 45.6 per cent of the free morphine and 48.4 per cent of the free codeine. In ingesting a curry meal or two containing various amounts of washed seeds (morphine intake: 200.4 to 1002 micrograms; codeine intake: 95.9 to 479.5 micrograms), the urinary morphine levels were found to be in the range 0.12 to 1.27 micrograms/ml urine and urinary codeine levels in the range 0.04 to 0.73 micrograms/ml urine. In any large scale screening for abuse of opiate drugs, the possibility of urinary alkaloids arising from consuming food containing poppy seeds must be considered and, if possible, eliminated. PMID- 1435126 TI - The fatal paracetamol dosage--how low can you go? AB - Popular texts and forensic literature pertaining to paracetamol toxicology advocate an acceptable minimal dose or lower limit of the blood level 'normally' associated with a fatal single overdose. A case of fatal, acute paracetamol poisoning from a minimal single dose, within the recommended therapeutic daily total and associated with a zero blood paracetamol level, is reported. It also emphasizes the common knowledge that the toxicological tabulated reference data available on fatal levels of most drugs is merely a guide. The proper interpretation of the analytical results thus requires the full consideration of the circumstances surrounding the death in each case. The clinico-pathophysiology and toxicology of paracetamol poisoning is briefly reviewed in an attempt to establish how low a fatal paracetamol dosage can go. The phenomenon of fatal dose and blood level is in a paracetamol limbo. PMID- 1435127 TI - Medical uses of corpses and the 'no property' rule. PMID- 1435128 TI - Guardianship Orders: a review of their use under the 1983 Mental Health Act. AB - This article reviews what has been reported in literature about the use of Guardianship Orders under the Mental Health Act 1983. Guardianship Orders were used infrequently in comparison with Sections 2, 3 and 4 of the Mental Health Act although the number of guardianship cases has increased three-fold since 1982. Elderly female patients with organic brain disease were the group on whom guardianship was most used either to support them in the community or to facilitate admission to residential care. Guardianship was rarely used to prevent hospitalization. Despite its many drawbacks, for a selected group of patients guardianship did appear to have advantages and was found to be worthy of consideration for practising clinicians and approved social workers. PMID- 1435129 TI - Reconviction following referral to a forensic clinic: the criminal justice outcome of diversion. AB - The criminal records of alleged offenders diverted from the normal process of prosecution were examined on average 31 months after assessment at a forensic clinic. Twenty-five per cent of those assessed reoffended. The apparent effect of treatment became statistically non-significant when other variables were controlled. It is argued that the case against the effectiveness of treatment remains 'non-proven' and that psychological benefits may accrue even in the absence of an effect on reconviction rate. PMID- 1435130 TI - Psychopathic disordered, mentally ill, and mentally handicapped sex offenders: a comparative study. AB - Although there currently exists a large amount of research on the characteristics and treatment of psychopathic disordered (PD) sex offenders, little if any empirical studies have addressed the mentally ill (MI) and mentally handicapped (MH) offender populations. A total of 106 PD, MI, and MH sex offender records from Rampton (Special) Hospital were reviewed for the study. Offender categories were compared by age of first documented sex offence, IQ at the time of admission, sex offence type, frequency of each offence type, history of violence during sex offences, age and gender of sex offence victims and number of victims for age and gender. Results revealed that 88 per cent of PD, 98 per cent of MI, and only 56 per cent of MH offenders' victims were female. Further analysis revealed that PD and MI offenders' victims were primarily female, with the largest proportion being pubescent and adult females. MH offender victims were primarily males and females under the age of 16. IQ correlated positively with history of violence during sexual assault and mean IQs were higher for 'violent' than 'non-violent' offenders in each offender category. A discussion of these and other significant findings, as well as implications for clinical treatment, is presented. PMID- 1435131 TI - Maximum-security hospital ward. PMID- 1435132 TI - Evaluation of therapeutic factors in group psychotherapy for 'non-sensical' shop lifters: a preliminary report. AB - There is a growing emphasis upon psychiatric involvement in management of 'non sensical' shop-lifters, those who steal items they neither want nor need. However there is very little description of, or research into, psychological treatment approaches for this group of clients. We report a preliminary study of the process of therapy in two out-patient psychotherapy groups for female 'non sensical' shop-lifters. Therapeutic factors in the group psychotherapy were evaluated using the method of Bloch et al. (1979) to assess the most important event in therapy. Results from nine subjects indicate that universality (realizing that one's problems are not unique) was rated as the most important aspect of therapy, with self-understanding the second most important. The implications of these findings for future provision and facilitation of therapy for this group of clients are discussed. PMID- 1435133 TI - Facial injuries due to criminal violence: a retrospective study of hospital attenders. AB - The material comprised 222 assault victims whose injuries required attention at the Departments of Oral Surgery and Ear, Nose, and Throat diseases, the Central Hospital in Falun or corresponding departments at the Karolinska Institutet, Stockholm or the University Hospital in Huddinge. Information was obtained from patient records. One hundred and thirty-eight patients had fractures and the remainder had flesh-wounds, haematomas or swellings. The most frequent fracture site was the nasal bone followed by the jaws. Forty-one per cent of the patients in Falun and 28 per cent in Stockholm reported the assaults to the police: in Falun the proportion of women victims who reported the assault was significantly higher than those who did not. The willingness to notify the police of the violence was not influenced by the use of drugs or the seriousness of the injuries. The study showed that violence in suburban Stockholm was aggravated: one-third of the patients in the study required hospitalization compared to a quarter in a rural area. PMID- 1435134 TI - The use of symptom validity testing in the diagnosis of functional sensory and memory deficits: a review. AB - This paper reviews the use of a modern psychophysical technique known as symptom validity testing. The technique employs a forced choice procedure providing an objective method for distinguishing between functional and organic aetiology in cases with sensory or memory deficit. The determination of functionality is by the objective demonstration that behaviour is controlled by stimuli in the sense modality in which the deficit is claimed. The data can be evaluated using conventional statistical techniques. The method is an advance on classical psychophysical methods as it does not depend upon the patient reporting whether he can or cannot perceive a single stimulus. PMID- 1435135 TI - A case of homicide by a psychiatric patient. PMID- 1435136 TI - [Use of pin spherical fixators in designing splint prostheses]. PMID- 1435137 TI - [Antimicrobial x-ray contrast articles]. AB - A procedure has been developed to prepare the radio-opaque polymer composition containing an antimicrobial substance that can be used in medicine. The findings of the antimicrobial activity of products made of the above composition are presented in the paper. PMID- 1435138 TI - [Improvement of metalloceramic dental prostheses]. AB - The paper outlines the procedure for producing an oxide film on cobalt-chromium alloy via triple heat treatment in vacuo. As a result, the oxide film consists mainly of cobalt oxide. The compositions of the prime and dentin layers of ceramics for cement dentures are described. PMID- 1435140 TI - [Portable x-ray diagnosis devices]. PMID- 1435139 TI - [Use of a universal ferro-probe pole locator PF-01 in medicine]. AB - The versatile II phi-01 flux-gate magnetic pole locator is intended for detecting and locating ferromagnetic foreign bodies in human tissue. The sensitivity of the device to magnetic field gradient is 4 mOe/cm on a large scale. The device can be used to locate a hypodermic needle at a distance of 50-90 mm, a sewing needle at 60-122 mm, a routine 7.62-mm bullet at 90 mm and a 5.6-mm bullet at 105 mm. PMID- 1435141 TI - [Improved technology for producing metalloceramic dental prostheses]. PMID- 1435142 TI - [Quality of removable plate (dental) prostheses]. PMID- 1435143 TI - [Development of a system controlling x-ray diagnostic devices]. AB - The purpose and criteria for efficiency (errors of anode voltage holding, tube current, and exposure) of the system controlling X-ray diagnostic devices are considered from theoretical and practical points of view. A microprocessor controlled variant of the controlling system developed for numerous existing six pulsed generators of the -3 type is outlined. The design and operation of the key circuit diagram of X-ray tube filament in the PEHA 50-6 microprocessor-controlled feeding device are shown in detail. PMID- 1435144 TI - [Extracorporeal perfusion system for temporary replacement of liver and spleen functions]. PMID- 1435145 TI - [A device for removal of curvilinear fixators]. AB - Osteosynthesis designed by A. I. Seppo is the method of choice in the treatment of fracture of the neck of the femur. Extracting the fixative elements with a standard extractor requires an additional trepanation of the bone. The authors have proposed an instrument to remove crivilinear fixatives that assume the proper direction of the extracting force, thus reducing the traumatism of the intervention. PMID- 1435146 TI - [A stand for rotational therapy]. PMID- 1435147 TI - [A BP-03 perfusion unit]. PMID- 1435148 TI - [A DISK Doppler analyzer of blood flow velocity]. PMID- 1435149 TI - [A "Geizer" device for prompt production of irrigation solutions and their use in surgery]. PMID- 1435150 TI - [A device for preparing cotton corks]. PMID- 1435151 TI - [A "Nadezhda 100" device for ultraviolet irradiation of blood]. PMID- 1435152 TI - [Optimization of the performance of electric defibrillation of the heart]. AB - The experimental study of 20 mongrel dogs has defined the values of threshold defibrillation (TDF) in 4 positions of voltage electrodes. Analysis of the findings by using the equivalent electric circuit has led to the conclusion that the increase of TDF values, even up to the absence of an effect produced by defibrillation, is due to the shunting of electromagnetic field lines, bypassing the myocardial component of the external circuit of an electrical pulse generator. PMID- 1435153 TI - [Systemic computerization of dialysis equipment]. PMID- 1435154 TI - Exercise-induced proteinuria is attenuated by indomethacin. AB - The role of the prostaglandin (PG) and renin-angiotensin hormonal systems in exercise-induced proteinuria following 30 min of submaximal, steady-state exercise was evaluated. Eight healthy males performed cycle ergometry at 75% of VO2peak on three occasions after the administration of a placebo (PLACEBO), a prostaglandin inhibitor (indomethacin, INDO), and an angiotensin converting enzyme inhibitor (captopril, CAPTO). Urine and blood samples were collected prior to, immediately following exercise, and over 40-min recovery. Data were evaluated for differences among drug treatments and measurement phases. During PLACEBO, exercise increased total protein excretion from 64.9 +/- 9.5 to 408.6 +/- 160.8 micrograms.min-1 (P < 0.05). PG inhibition with INDO significantly attenuated the increased proteinuria due to exercise (149.2 +/- 64.0 micrograms.min-1). The proteinuric response to exercise was not altered by CAPTO. Resting plasma renin activity (PRA) and aldosterone (ALDO) were significantly reduced during the INDO trial. Although the twofold increment in ALDO with exercise remained intact during the INDO trial, the PRA response to exercise was significantly blunted. No treatment differences were observed for mean arterial pressure, sodium excretion, urine flow, or creatinine clearance values during rest or exercise. These results suggest that the proteinuria associated with steady-state exercise is PG dependent and not related to hemodynamic influences. PMID- 1435155 TI - Musculoskeletal strength and serum lipid levels in men and women. AB - There currently is inconsistent information regarding the role that musculoskeletal strength (one component of musculoskeletal fitness) may have in lipid and lipoprotein metabolism, and consequently the risk of cardiovascular disease. Results of existing studies have been conflicting and have been influenced by several weaknesses. We provide cross-sectional analyses of the relation between muscular strength and serum lipid and lipoprotein status in a group of 1,193 women and 5,460 men. The large proportion of patients were not involved in formal weight training. As part of a preventive medical examination, patients were tested for maximal upper and lower body strength (one repetition maximum (1RM) bench and leg press). Fasting serum total cholesterol (TC), low density lipoprotein cholesterol (LDLC), triglyceride (TG), and high density lipoprotein (HDLC) were evaluated for their relation to muscle strength, after adjusting for simultaneous associations with age, body composition, and cardiovascular fitness. Results showed no association between muscular strength and serum TC or LDLC for either men or women and a direct association between upper and lower body strength and TG in men. The direct association between strength and TG in women was not significant. A statistically significant inverse association was seen between muscular strength and HDLC in men only. These data suggest no beneficial effect, and perhaps an adverse association of muscular strength on lipid and lipoprotein status. PMID- 1435156 TI - Effect of pedal rate on cardiorespiratory responses during continuous exercise. AB - The role of cycle ergometer pedal rate on the gradual increase in ventilation (VE), heart rate (HR), and oxygen uptake (VO2) accompanying continuous submaximal exercise is unknown. To examine this problem, five trained males (VO2peak = 4.00 +/- 0.27 l.min-1) performed 45 min of moderate intensity (MI, 127 W) and high moderate intensity (HMI, 166 W) cycle ergometry both at pedal rates of 60 rpm and 90 rpm. Power output and pedal rate had an additive effect on the overall mean responses for VE, HR, and VO2, producing significantly higher values as power output and pedal rate increased. During continuous exercise, VE, HR, and VO2 increased progressively from the 10th to the 45th minute for all tests. However, the rates of increase and factors modifying the VE, HR, and VO2 responses were different. HR increased during all exercise tests an average of 10.8% independent of power output and pedal rate. VE increased 7.4% during MI exercise and 10% during HMI exercise independent of pedal rate. Similar power output dependent responses were observed for rectal temperature (Tr) and blood lactate. VO2 increased 4.4% for MI and HMI exercise at 60 rpm, and 8.2% for the same power outputs at 90 rpm, respectively. Increases in Tr, the oxygen cost of pulmonary ventilation and fat oxidation, and lactate removal were estimated to account for only 31-36% of the slow rise in VO2 for any single test. This suggests that 64 69% of the rise in VO2 was due to factors related to muscle use.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435157 TI - Effect of varying levels of hypohydration on responses during submaximal cycling. AB - The effect of varying levels of hypohydration on hemodynamic, cardiorespiratory, and metabolic responses to progressive incremental submaximal cycling was examined in nine male subjects. Subjects cycled in a neutral (22 degrees C) environment under euhydration (EU), moderate hypohydration (MH), and severe hypohydration (SH). To achieve the desired level of hypohydration, subjects cycled at 50% VO2max for 1.5 h in a 38 degrees C environment on two separate occasions, 36 h prior to testing. Mean (+/- SE) percent losses in body weight from baseline during EU, MH, and SH were 0.6 +/- 0.3%, 3.3 +/- 0.1%, and 5.6 +/- 0.4%, respectively. Ventilation, O2 uptake, respiratory exchange ratio, heart rate, plasma free fatty acids, plasma glycerol, blood lactate, and hematocrit were not significantly altered by hypohydration. During EU, hemoglobin concentration was significantly lower than during both MH and SH, but no significant difference was observed for plasma volume loss. Plasma glucose was significantly higher during SH compared with EU and MH. These results suggest that hypohydration of up to 5.6% caused by exercise and fluid manipulation over 36 h does not alter cardiorespiratory or blood lactate responses during progressive incremental submaximal cycling in a neutral environment. However, hepatic metabolism may be altered during hypohydration as indicated by higher plasma glucose levels. PMID- 1435158 TI - Physiological response to cycling with both circular and noncircular chainrings. AB - The purpose of this study was to compare physiological variables of endurance trained cyclists riding with four different chainring designs: round, Shimano Biopace, and two engineered ellipse designs. The ellipse designated Eng10 had the crank arm oriented 10 degrees forward of the major (i.e. longer) axis. Eighty degrees further forward, along the minor axis, was the crank arm orientation for the second ellipse, Eng90. With the major to minor axis ratio of 22.9 cm/16.8 cm (1.36), both ellipses imposed a crank angular velocity variation of 27% relative to the highest velocity assuming constant chain velocity. Best described as a skewed ellipse (i.e., major and minor axes not perpendicular), the Biopace had a major to minor axis ratio of 1.09 thus giving a crank angular velocity variation of 8%. Eleven male cyclists rode at a high (80% of maximum VO2) and a low (60% of maximum VO2) workrate using each chainring. The study was conducted over four consecutive days with the presentation order of the chainrings randomized. Open circuit spirometry was used to collect continuous respiratory data. Heart rate, blood lactate, and cadence values also were measured. None of the physiological variables including rates of oxygen consumption showed significant differences among the chainrings. Thus, the gross efficiency of cycling was not improved by any of the noncircular chainrings. For cycling events where efficiency is a determinant of performance, the noncircular chainrings do not offer any advantage over round chainrings. PMID- 1435159 TI - Effect of cadence on the economy of uphill cycling. AB - Competitive cyclists generally climb hills at a low cadence despite the recognized advantage in level cycling of high cadences. To test whether a high cadence is more economical than a low cadence during uphill cycling, nine experienced cyclists performed steady-state bicycling exercise on a treadmill under three randomized trials. Subjects bicycled at 11.3 km.h-1 up a 10% grade while 1) pedalling at 84 rpm in a sitting position-84 Sit, 2) pedalling at 41 rpm in a standing position-41 Stand, and 3) pedalling at 41 rpm in a sitting position 41 Sit. Heart rate (HR), oxygen consumption (VO2), ventilation (VE), and respiratory exchange ratio were measured continuously during 5-min trials and averaged over the last 2 min. Additionally, rating of perceived exertion was recorded during the fifth minute of each trial, and blood lactate concentration was recorded immediately before and after each trial. Significantly lower values for HR, VO2 and VE were recorded during 84 Sit (164 +/- 3 bpm, 51.8 +/- 0.8 ml.min-1 x kg-1, 94 +/- 5 l.min-1) than for either the 41 Stand (171 +/- 2 bpm, 53.1 +/- 0.7 ml.min-1 x kg-1, 105 +/- 6 l.min-1) o 41 Sit (168 +/- 2 bpm, 53.1 +/ 0.8 ml.min-1 x kg-1, 101 +/- 6 l.min-1) trials. No other differences were noted between trials for any of the measured variables. We conclude that uphill cycling is more economical at a high versus a low cadence. PMID- 1435160 TI - Physiological, anthropometric, and training correlates of running economy. AB - Potential physiological, anthropometric, and training determinants of running economy (RE) were studied in a heterogeneous group of habitual distance runners (N = 188, 119 males, 69 females). RE was measured as VO2 (ml.kg-1.min-1) during level treadmill running at 161 m.min-1 (6 mph) (VO2-6). Examined as potential determinants of RE were heart rate and ventilation while running at 6 mph (HR6, VE6), VO2max (ml.kg-1 x min-1), % fat, age, gender, height, weight, estimated leg mass, typical training pace, training volume, and sit-and-reach test performance. RE was entered as the dependent variable and the potential determinants as independent variables in zero-order correlation and multiple regression analyses. Zero-order correlation analysis found VO2max, HR6, and VE6 to be significantly, positively correlated with VO2-6 (P < 0.001). Multiple regression analysis, in which the independent effect of each predictor variable was examined, revealed VO2-6 to be positively correlated with VO2max (P < 0.001), HR6 (P < 0.001), VE6 (P < 0.001), and age (P < 0.05) and negatively correlated with weight (P < 0.01). These findings indicate that, in a diverse group of runners, better RE (VO2-6) is associated with lower VO2max, lower submaximal exercise VE and HR, lower age, and greater weight. PMID- 1435161 TI - Transfer of tennis racket vibrations onto the human forearm. AB - One of several factors suspected in the development of lateral epicondylitis, often referred to as tennis elbow, is the impact-induced vibration of the racket and-arm system at ball contact. Using two miniature accelerometers at the wrist and the elbow of 24 tennis players, the effects of 23 different tennis racket constructions were evaluated in a simulated backhand stroke situation. The influences of body weight, skill level, and tennis racket construction onto the magnitude of vibrations at wrist and elbow were investigated. Amplitudes, integrals, and fourier components were used to characterize arm vibration. More than fourfold reductions in acceleration amplitude and integral were found between wrist and elbow. Off-center as compared with center ball impacts resulted in approximately three times increased acceleration values. Between subjects, body weight as well as skill level were found to influence arm vibration. Compared with proficient players, a group of less skilled subjects demonstrated increased vibration loads on the arm. Between different racket constructions, almost threefold differences in acceleration values could be observed. Increased racket head size as well as a higher resonance frequency of the racket were found to reduce arm vibration. The vibration at the arm after ball impact showed a strong inverse relationship (r = -0.88) with the resonance frequency of tennis rackets. PMID- 1435162 TI - Effects of taper on swim power, stroke distance, and performance. AB - Competitive swimmers progressively reduce training volume or "taper" prior to an important competition in an effort to improve performance capabilities. The purpose of the current study was to determine the effects of taper upon factors associated with swim performance. Twelve intercollegiate swimmers were tested before and after taper in preparation for their season-ending meet. Power during a tethered sprint swim increased significantly (P < 0.05) by approximately 5% with taper. No significant changes occurred in distance per stroke, oxygen consumption, and post-exercise blood lactate level during a 182.9-m submaximal swim with taper. Five swimmers were additionally tested after shaving exposed body hair upon completion of taper. Swim power did not increase further with hair removal. In contrast, shaving significantly increased distance per stroke (P < 0.05) by approximately 5%. These data indicate that reduced training specifically improves swim power; however, removing exposed body hair after taper may additionally enhance performance capabilities by increasing distance per stroke. PMID- 1435163 TI - Effect of age and menopausal status on cardiorespiratory fitness in masters women runners. AB - Forty-nine trained masters women endurance runners (mean = 42 km.wk-1) between the ages of 35 and 70 yr (mean = 46.4 +/- 8.3) were tested on a treadmill to examine cardiorespiratory fitness (VO2max and VO2 submax) in relation to age, training, and menopausal status. Although VO2max was lower with increasing age, no age group differences occurred in VO2 submax at 5.4 km.h-1, 8% treadmill grade. The younger runners (35-39 and 40-44 yr) had significantly higher VO2max than the other 5-yr competitive age groups (45-49, 50-55, 55-70 yr) (P < 0.01). HR max did not differ across age, but HR submax was higher with increasing age. Premenopausal, transitional, and post-menopausal women were not significantly different on any exercise variable when age and/or training differences among the groups were statistically controlled. A decrease in VO2max of 0.58 ml.kg-1 x min 1 x yr-1 was determined (r = -0.62). It was concluded that 1) these highly trained women runners had higher cardiorespiratory fitness than previously reported for women of comparable age, 2) menopausal status did not effect cardiorespiratory fitness when age and training were accounted for, and 3) regular physical training seems to prevent age-related changes in HR max in women, but not age-related changes in maximal oxygen uptake. PMID- 1435164 TI - Running on land and in water: comparative exercise physiology. AB - The effect of water immersion on cardiorespiratory and blood lactate responses during running was investigated. Wearing a buoyant vest, 10 trained runners (mean age 26 yr) ran in water at four different and specified submaximal loads (target heart rates 115, 130, 145, and 155-160 beats.min-1) and at maximal exercise intensity. Oxygen uptakes (VO2), heart rates, perceived exertion, and blood lactate concentrations were measured. Values were compared with levels obtained during treadmill running. For a given VO2, heart rate was 8-11 beats.min-1 lower during water running than during treadmill running, irrespective of exercise intensity. Both the maximal oxygen uptake (4.03 vs 4.60 1 x min-1) and heart rate (172 vs 188 beats.min-1) were lower during water running. Perceived exertion (legs and breathing) and the respiratory exchange ratio (RER) were higher during submaximal water running than during treadmill running, while ventilation (1 x min-1) was similar. The blood lactate concentrations were consistently higher in water than on the treadmill, both when related to VO2 and to %VO2max. Partly in conformity with earlier cycle ergometer studies, these data suggest that immersion induces acute cardiac adjustments that extend up to the maximal exercise level. Furthermore, both the external hydrostatic load and an altered running technique may add to an increased anaerobic metabolism during supported water running. PMID- 1435165 TI - The effect of salbutamol on performance in elite nonasthmatic athletes. AB - The effect of salbutamol on performance was studied in seven male nonasthmatic highly trained (VO2max > or = 60 ml.kg-1 x min-1) cyclists. Salbutamol (S = 2 puffs = 200 micrograms) or placebo (P) was administered by metered-dose inhaler, through a spacer device, 20 min prior to testing in a double-blind, randomized cross-over design. Testing sessions on a cycle ergometer included the measurement of maximal oxygen uptake (VO2max), peak power, maximal heart rate, and pulmonary function. A timed sprint to exhaustion was performed after 45 min of exercise at 70% of VO2max, and a Wingate anaerobic test was used to measure total work and peak power. There was a nonsignificant decrease in VO2max (P = 63.5 +/- 3.2; S = 62.6 +/- 3.3 ml.kg-1 x min-1). No difference was found in peak power, maximum heart rate, endurance sprint time, Wingate peak power, or total work. After an anticipated baseline increase was taken into account, the pattern of change in FEV1 over time did not differ between salbutamol and placebo. It was concluded that a therapeutic dose of aerosol salbutamol does not have an ergogenic effect in elite nonasthmatic athletes, and it is therefore recommended that inhaled salbutamol continue to be permitted in international competition for individuals with exercise induced bronchospasm. PMID- 1435166 TI - Variability of some objective measures of physical activity. AB - The purpose of this study was to determine how many days subjects should be monitored to provide an estimate of habitual physical activity in employed men engaged in a wide range of occupations. Caloric intake, movement recorders (accelerometers and pedometers), and heart rate were the measurements studied in 30 subjects who were monitored during their waking hours for 7 continuous days. A repeated measures ANOVA showed no significant difference between days (P > 0.05) for any of the measures when only weekdays were compared. However, when weekend days were included a majority of the measures showed a significant F-ratio (P < 0.05). An estimate was made of the number of days required to measure a 7-d period with less than 5% error. The average for all the different measures was 4.9 d. It appears that at least 5 or 6 d are needed to minimize the intra individual variance a reasonable degree. Weekdays as well as weekend days need to be included. PMID- 1435167 TI - Predictors of over- and underachievement of age-predicted maximal heart rate. AB - The age-predicted maximal heart rate (PMHR) formula, 220--age, is frequently used for identifying exercise training intensity, as well as determining endpoints for submaximal exercise testing. This study was designed to identify variables discriminating those with actual maximal heart rates considerably above or below that predicted from the 220--age equation. Subjects included 2010 men and women ranging in age from 14 to 77 yr. Stepwise discriminant analysis was performed using maximal heart rate error groups as the dependent variable, and selected preexercise test characteristics as predictors. The HR error groups were based on the difference between the measured and PMHR as follows: below (> or = 15 beats.min-1 below PMHR), within (+/- 14 beats.min-1 of PMHR), and above (> or = 15 beats.min-1 above PMHR). A contrast of the below and above groups identified age, resting HR, body weight, and smoking status as predictors of group membership (P < 0.01) for both men and women. The overall canonical correlation was 0.282 and 0.294 for the men and women, respectively. Older age, higher resting HR, lower weight, and non-smoking were related to the above group, while the inverse was related to the below group. Standardized coefficients suggest that age and resting heart rate for the men, and age and smoking status for the women were the most potent variables for discriminating extreme deviations between measured and PMHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435168 TI - Cardiovascular benefits of physical activity. PMID- 1435169 TI - Case presentation: painless arm swelling in a high school football player. AB - Paget-Schroetter syndrome, more commonly called "effort thrombosis," has been well documented in the literature but is considered an uncommon cause of morbidity in the athletic population. We describe a case of axillary-subclavian vein thrombosis ("effort thrombosis") that presented as painless arm swelling in a high school football player. This case reviews the presentation, diagnosis, and management of this difficult problem in a young athlete. PMID- 1435170 TI - Bone density in postmenopausal women: high impact vs low impact exercise. AB - This 1 year study examined the effect of high impact and low impact activities on bone mineral density (BMD) at the lumbar vertebrae (L2-L4) in healthy, sedentary, early postmenopausal women. Fifteen subjects whose postmenopausal status was verified by the blood levels of follicle stimulating hormone (FSH) and estradiol were chosen. These subjects were tested on the following variables: BMD via dual photon absorptiometry, heart rate response to the Balke treadmill test, percent fat via skinfolds, and a 3-d dietary analysis. Subjects were matched and then assigned randomly to one of three groups: (a) a control nonexercising group, (b) a low impact exercise group, and (c) a high impact exercise group. The control nonexercising group experienced a significant linear decrease in BMD during the study (F = 12.63, P = 0.002). Both the low and high impact exercise groups maintained BMD during the study (F = 0.04, P = 0.85; F = 1.08, P = 0.31, respectively). The difference in BMD between the low impact and the high impact exercise groups was not significant (F = 0.36, P = 0.55). In conclusion, 20 min of moderate intensity low impact or high impact exercise 3 d.wk-1 for 1 yr is effective in maintaining BMD in early postmenopausal women. PMID- 1435171 TI - Cancer and the protective effect of physical activity: the epidemiological evidence. AB - Studies of activity and all-cancer mortality have inconsistent findings and are difficult to interpret, largely because cancer refers not to one disease but to many distinct, site-specific diseases. However, mounting evidence suggests that physical activity may be associated with decreased mortality from and incidence of certain types of cancers. In 15 of 18 studies, higher levels of occupational and/or recreational activity were inversely related to colon cancer incidence and mortality. One major study found activity to be negatively related to occurrence of breast cancer, and conflicting findings exist regarding the association between activity and prostatic cancer. Given the consistency in the direction and magnitude of the findings regarding activity and colon cancer, the presence of appropriate temporal relationships between measured exposure and outcome, the suggestion of dose-response relationships and the existence of plausible biological mechanisms, including increased transit time and gut motility, the evidence supports the conclusion that activity is protective against colon cancer. Although that protective effect may be small, the attributable risk of colon cancer associated with inactivity may be quite high given the prevalence of inactivity in Western societies. PMID- 1435172 TI - Effects of exercise training on plasminogen activator inhibitor activity. AB - Plasminogen activator inhibitor (PAI) activity, an important regulator within the fibrinolytic system, has been shown to be a risk indicator for venous and arterial thrombosis. The present study aimed to test the effects of exercise training on PAI activity, and to link possible changes in PAI activity to changes in cardiovascular fitness, body composition, and the lipid profile. Four groups of previously sedentary subjects were studied thrice in an 8-month period. A long term training group (N = 11) trained during the entire 8-month period. A detraining group (N = 14) trained for 4 months and then reverted to sedentary habits. A postponed training group (N = 16) trained only during the second 4 month period, and a no-training control group (N = 9) remained untrained throughout the entire 8-month period. PAI activity always decreased in response to training, but the training effects were small and spontaneous seasonal shifts in PAI activity of the control groups clouded their interpretation. Furthermore, detraining failed to influence PAI activity and training-induced changes in PAI activity were not related to simultaneous changes in maximal oxygen consumption, diastolic blood pressure, triglycerides, or percentage body fat, and inconsistently related to the training-induced changes in LDL-cholesterol and HDL cholesterol. The occurrence of simultaneous changes in body fat, blood pressure, and the lipid profile underscores the potential of regular exercise to protect against cardiovascular disease. Whether these beneficial effects are accompanied by changes in the fibrinolytic system remains to be proven. PMID- 1435174 TI - Blood pressure responses to LBNP in nontrained and trained hypertensive rats. AB - To study the influences of 16 wk of endurance training on the reflex regulation of resting blood pressure, nontrained (NT) and trained (T) female hypertensive rats (SHR) were subjected to conditions of lower body negative pressure (LBNP). Measurements of muscle cytochrome oxidase activity and run time to exhaustion indicated that the animals were endurance trained. The rats (NT = 6, T = 7) were tranquilized with 300-600 micrograms.kg-1 diazepam (IV) before heart rates and blood pressures were measured over a range of 2.5-10.0 mm Hg of negative pressure. When subjected to conditions of LBNP, the reflex tachycardia of the T group was greater than the NT at the lower (-2.5 and -5.0 mm Hg) negative pressures. Although arterial pressure declines were similar in both groups, the T group experienced significantly less of a decline in central venous pressure than the NT animals. When chlorisondamine was used as a ganglionic blocker (2.5 mg.kg 1, IV), the fall in CVP at 10 mm Hg negative pressure was greater for the NT group while the fall in the initial systemic arterial pressure was more for the T group. From these results we concluded that training had altered the interaction between cardiopulmonary and arterial baroreflexes in these hypertensive rats and a nonneural component had been altered such as cardiac function. PMID- 1435173 TI - Relative changes in maximal force, EMG, and muscle cross-sectional area after isometric training. AB - The purpose of this experiment was to determine whether training-induced increases in maximal voluntary contraction (MVC) can be completely accounted for by increases in muscle cross-sectional area. Fifteen female university students were randomly divided into a control (N = 7) and an experimental (N = 8) group. The experimental group underwent 8 wk of isometric resistance training of the knee extensors of one leg; the other leg was the untrained control. Training consisted of 30 MVC.d-1 x 3 d.wk-1 x 8 wk. Extensor cross-sectional area (CSA), assessed by computerized tomographic (CT) scanning of a cross-sectional slice at mid-thigh, was used as a measure of muscle hypertrophy. After 8 wk of training, MVC increased by 28% (P < 0.05), CSA increased by 14.6% (P < 0.05), and the amplitude of the electromyogram at MVC (EMGmax) was unchanged in the trained leg of the experimental subjects. The same measures in the untrained legs of the experimental subjects and in both legs of the control subjects were not changed after training. Although there was an apparent discrepancy between the increase in MCV (28%) and CSA (14.6%), the ratio between the two, the specific tension (N.cm-2), was not significantly different after training. As a result of these findings, we conclude that in these subjects there is no evidence of nonhypertrophic adaptations to resistance training of this type and magnitude, and that the increase in force-generating capacity of the muscle is due to the synthesis of additional contractile proteins. PMID- 1435175 TI - Reduction in LBNP tolerance following prolonged endurance exercise training. AB - Eight young men underwent an 8-month endurance exercise training program. Prior to and following the training program, the subjects' maximal oxygen uptake (VO2max), total blood volume (TBV) and plasma volume (PV), tolerance to lower body negative pressure (LBNP) assessed by the cumulative stress index (CSI) to presyncope, and their hemodynamic responses to 0 to -45 torr LBNP was determined. Hemodynamic measures included rebreathe carbon dioxide cardiac output (Qc), heart rate (HR), directly measured arterial blood pressures (ABP), and strain gauge determination of forearm blood flow (FBF) and leg volume changes (delta LgV). Calculated values of stroke volume (SV), forearm, vascular resistance (FVR), and peripheral vascular resistance (PVR) were made. Following training, each subject had an increased VO2max (mean = +27.4%, P < 0.001), TBV (mean = +15.8%, P < 0.02), and PV (mean = +16.5%, P < 0.02) and each subject had a decreased tolerance to LBNP (mean CSI = -24%, P < 0.001). Stepwise linear regression identified that the major factors to significantly predict the decreased CSI pre- to post-training were a reduced response of PVR to LBNP from -15 to -45 torr (Model R2 = 0.853), the delta TBV (model R2 = 0.981), and the greater post training reduction in SBP to LBNP of 0 to -45 torr (model R2 = 1.0). These data suggest that physiologic adaptations associated with the increased VO2max and TBV resulting from a prolonged endurance exercise training program can alter the reflex control of vasomotion and cardiac output during LBNP and reduce the LBNP tolerance. PMID- 1435176 TI - Cardiac response to acute coronary artery occlusion in exercise-trained dogs. AB - Exercise training is thought to exert a beneficial effect on cardiovascular function, but its effect in the normal heart following acute coronary artery occlusion is still uncertain. Studies were performed in 12 untrained (UT) and 14 endurance-trained (ET) pentobarbital anesthetized dogs. Left ventricular pressure (LVP), heart rate (HR), percent regional myocardial segmental shortening (%SL), and peripheral coronary pressure (PCP) distal to the occlusion were measured during control conditions and during a 2-min circumflex artery occlusion (CAO). During CAO, LVP, dP/dtmax, and %SL in the ischemic region were significantly reduced in both UT and ET dogs. There was no significant difference between the two groups. In addition, PCP decreased to 27 +/- 5 mm Hg and 26 +/- 9 mm Hg in the UT and ET groups, respectively, during CAO indicating no difference in coronary collateral perfusion between the groups. Regional myocardial blood flow was measured using tracer microspheres in eight of the UT and six of the ET dogs, and the decrease in blood flow to the ischemic zone during CAO was similar in both groups. These results indicate that 12-wk of endurance training does not exert a protective effect on myocardial contractile function or on myocardial perfusion in the central ischemic region during CAO in the anesthetized dog. PMID- 1435177 TI - EMG and mechanical changes during sprint starts at different front block obliquities. AB - The effect of decreased front block obliquity on start velocity was studied during sprint starts. The electromyographic (EMG) activity of the medial gastrocnemius (MG), the soleus (Sol), and the vastus medialis (VM) was recorded and analyzed at a 70 degrees, a 50 degrees, and a 30 degrees angle between the foot plate surface and the horizontal. Integrated EMGs (IEMG) were compared with muscle length changes in the MG and Sol in relation to foot and knee movements. The results indicate that decreasing front block obliquity significantly (P < 0.05) increases the start velocity without any change to the total duration of the pushing phase and the overall EMG activity. This improvement in sprint start performance is associated with the enhanced contribution of the MG during eccentric and concentric phases of calf muscles contraction. In the "set position" the initial length of MG and Sol is increased at 50 degrees and 30 degrees as compared with 70 degrees. The subsequent stretch-shortening cycle is improved and contributes more effectively to the speed of the muscle shortening. Moreover, lengthening these muscles during the eccentric phase stretches the muscle spindles, and the reflex activities that contribute to the observed increase in the MG IEMG, are present when the slope of the block is reduced. The results indicate that decreasing front block obliquity induces neural and mechanical modifications that contribute to increasing the sprint start velocity without any increase in the duration of the pushing phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435178 TI - Metabolic and anthropometric changes with weight cycling in wrestlers. AB - Repeated cycles of weight loss and regain have come to be known as weight cycling. This phenomenon is frequently observed in athletes who must meet specific weight categories to qualify for competition. The purpose of this study was to determine the metabolic and anthropometric changes that occur with rapid weight loss/regain cycles in competitive wrestlers. Collegiate wrestlers were divided into two groups, "cyclers" (N = 8) and "noncyclers" (N = 6), based on their reported dieting history. Measurements included a 3-d diet record, resting energy expenditure (REE), skinfold and girth measures, and biochemical tests at three time points: preseason, peak season, and off-season. All anthropometric measures changed with time, and a diet group by time interaction was observed for the trunk to extremity skinfolds ratio (T/E) (P < 0.05), with greater fat loss and regain from the trunk area of the cyclers. There were no differences in REE within or between groups. Serum triiodothyronine (T3) values decreased over time (P < 0.01). Large weight losses appear to have occurred due to both dieting and short-term dehydration, and although physiological changes were observed, a training effect may have overridden any metabolic influence of weight cycling. PMID- 1435179 TI - Physiological aspects of swimming performance for persons with disabilities. AB - The purpose of this study was to evaluate the various factors involved in the performances of three groups of swimmers with disabilities. These factors were average VO2max (Av-VO2max) measured during swimming and gliding factors measured by the passive drag. Thirty-four swimmers with disabilities were assigned into three groups ranging from more disabilities to fewer disabilities. The first group (G I) included 13 subjects in wheelchairs, the second group (G II) 10 subjects walking with technical aids, and the third group (G III) 11 swimmers with disabilities walking without any help. For G I, the performances and Av VO2max were lower (P < 0.05) than for G II and G III while the passive drag was higher than for G III (P < 0.05). The performances, Av-VO2max, and passive drag were not statistically different between G II and G III. Some of the swimmers had a pronounced amyotrophia of the lower extremities (i.e., reduced volume of inactive muscles). The height from the top of the head to the beginning of the bilateral amyotrophia was called "height without amyotrophia" (HWA). In the whole group, passive drag was not related to the mass or the height but to the ratio mass/HWA (r = 0.71, P < 0.01). However, within each group, passive drag was mainly related to the mass (r = 0.63, 0.78, 0.62, P < 0.01, for G I, G II, and G III respectively). Performances of a 100-m and 400-m swim were mainly related to Av-VO2peak (r = 0.81 and 0.79, P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435180 TI - Endurance training enhances critical power. AB - The present investigation was conducted to determine whether critical power (CP) assesses the ability to perform continuous aerobic exercise and to determine whether training-induced changes in aerobic endurance are reflected by changes in the slope, but not the y-intercept of the CP function. Twelve healthy, active, but untrained male students (mean age +/- SD = 19.1 +/- 0.8 yr) undertook 8 wk of cycle ergometer endurance training (30-40 min a day, three times a week) at an intensity corresponding to their CP. Six control subjects of similar age and initial training status refrained from regular exercise for the same period. Before and immediately following the training period, each of the 18 participants completed three cycle ergometer tests to determine their CP function, an incremental exercise task to establish their maximal oxygen uptake (VO2max), and 40 min of continuous cycle ergometry at or near their calculated CP. CP was significantly correlated with endurance time at 270 W (r = 0.65, P < 0.05) and with the mean power that could be maintained for 40 min (r = 0.87-0.95, P < 0.01), but overestimated the latter by less than 6%. In response to endurance training, CP increased from a mean of 196 +/- 40.9 W to 255 +/- 28.4 W (31%) (ANCOVA, P < 0.01), while the mean power output maintained for 40 min of exercise increased from 190 +/- 34.5 W to 242 +/- 34.9 W (28%). VO2max increased from 49.2 +/- 7.8 ml.kg-1.min-1 to 53.4 +/- 6.4 ml.kg-1.min-1 (8.5%) (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435181 TI - Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet. AB - Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet. Med. Sci. Sports Exerc., Vol. 24, No. 11, pp. 1290-1297, 1992. The effect of a lacto-ovo vegetarian (V) and a mixed, meat-rich (M) diet on the level of serum sex hormones, gonadotropins, and endurance performance of eight male endurance athletes was investigated in a 2 x 6 wk cross-over study. The energy contribution from carbohydrate, fat, and protein was 58%, 27%, and 15% on the V diet and 58%, 28%, and 14 E% on the M diet. For total fasting serum testosterone (T) there was a significant interaction between diet and time (P < 0.01). Thus, the V diet resulted in a lower total T level (13.7, 9.8-32.4 nmol.l-1) (median and range) compared with the M diet (17.4, 11.8-33.5 nmol.l-1). During exercise after 6 wk on the diets total T was also significantly lower on the V than on the M diet (P < 0.05). Serum free testosterone, however, did not differ significantly during the 6 wk dietary intervention periods and neither did serum concentrations of sex hormone binding globulin, dihydrotestosterone, dehydroepiandrosterone sulphate, 4-androstenedione, estrone, estradiol, estrone sulphate, or gonadotropins. Endurance performance time was higher for six and lower for two after the mixed diet compared with the vegetarian diet. This was not significant, however. In conclusion, 6 wk on a lacto-ovo vegetarian diet caused a minor decrease in total testosterone and no significant changes in physical performance in male endurance athletes compared with 6 wk on a mixed, meatrich diet. PMID- 1435182 TI - Validity of bioelectrical impedance equations for estimating fat-free weight in lean males. AB - The present study examined the validity of bioelectrical impedance (BIA) equations for estimating fat-free weight (FFW) in lean males (X +/- SD = 9.1 +/- 2.2% fat) by comparing the estimates with values obtained from underwater weighing. Sixty-eight Caucasian male volunteers served as subjects. Cross validation analyses included examination of the constant error (CE), standard error of the estimate (SEE), r, and total error (TE). The results indicated that the equations of Oppliger et al. (16), which resulted in small TE (1.70 kg) and CE (-0.02 kg) values, most accurately estimated FFW. Simple linear regression showed that FFW was more highly correlated with body weight (BW) (r = 0.98, P < 0.0001) and resulted in a lower SEE (1.68 kg) than either height2/resistance (Ht2/R) (r = 0.81, P < 0.0001; SEE = 5.12 kg) or the independent variable (weight x resistance)/height2 [WR/Ht2] utilized by the manufacturer of the BIA analyzer (r = 0.15, P > 0.05; SEE = 8.59 kg). Multiple regression showed that when WR/Ht2, Ht2/R, resistance, body mass index, Ht2, and/or Ht was added to the prediction equation, which utilized BW alone, they accounted for less than 1% additional variance and reduced the SEE by < or = 0.16 kg. The results indicated that BW alone estimated FFW as accurately as any of the BIA equations in lean males. PMID- 1435183 TI - Accuracy of RPE from graded exercise to establish exercise training intensity. AB - The purpose of this investigation was to examine the accuracy of an exercise intensity prescription based upon perceptual responses obtained during a graded exercise test. Fifteen physically active men completed a graded exercise test (GXT) on a motor driven treadmill. Heart rate (HR), oxygen uptake (VO2), and RPE were measured each minute. An RPE intensity prescription was calculated as 75% of heart rate reserve from the GXT heart rate and RPE data. A minimum of 48 h later the subjects completed 10 min of exercise (EXT) on a level treadmill at the prescribed RPE. The subjects set the treadmill speed to elicit an exercise intensity equal to the prescribed perception of effort. There were significant mean differences (P < 0.05) in heart rate between the GXT (161.8 +/- 1.3) and EXT (154.9 +/- 4.5). However, by minute 6 the subjects were within four beats.min-1 of the target heart rate. There were no significant differences (P > 0.05) between GXT and EXT for VO2 (36.1 +/- 5.2, 33.1 +/- 6.4) and VE (64.1 +/- 10.8, 58.4 +/- 13.5) respectively. The present investigation demonstrates that a subject's perceptual response to a GXT can be used to accurately prescribe exercise intensity during level treadmill running. The intensity selected was within a typical range used for exercise prescription. The advantage of RPE as a method of exercise prescription is that an individual does not need to stop during exercise and measure a heart rate, but can make pace adjustments while exercising based solely upon the perception of effort. PMID- 1435184 TI - [Infection by the human immunodeficiency virus and leprosy]. AB - The author is reviewing the literature about the association HIV infection and leprosy. So he concludes: 1) there is no correlation between leprosy incidence and HIV infection incidence, despite similarity as far as immuno-system is concerned. 2) Effect of HIV infection on leprosy demands further studies of nervous leprosy pathology. 3) Tendency to increase of such and association is foreseeable, speaking of epidemiocity in developing countries as well as in leprosy foci in Southern Asia and India. PMID- 1435186 TI - [Vesicovaginal fistulas: etiopathogenic and therapeutic aspects in Senegal]. AB - Obstetrical vesico-vaginal fistulas are still very common in developing countries, because of to the difficulties of medical facilities. From a series of 123 cases recorded during 6 years, we analyse their epidemiological, anatomo clinical, and therapeutic aspects. A simplified classification is purposed. PMID- 1435185 TI - [Chronic hepatic cytolysis syndrome in southern Africa]. AB - Accidental discovery of a moderate and durable increase of transaminases in an asymptomatic patient is a more frequent possibility thanks to the development of methodological case findings activities. Most of the time, it is an isolated anomaly of which import and consequences have been already reviewed and published. Steatosis and chronic hepatitis are, by far, the most frequent etiologies in Western Countries. But the right importance of that syndrome in tropical hepatology has not been yet described. If we want to transpose results and what has to be done namely liver biopsy, to African medical practice, we have to take into due consideration local pathology, diagnosis facilities and/or therapeutic possibilities. The present article reviews the present knowledge on chronic liver cytolysis syndrome and discusses its interest in tropical Medicine. PMID- 1435187 TI - [Acute periurethritis: 155 cases]. AB - Severe complications of urethral stricture, acute peri-urethral phlegmon can be localized or diffuse. They are characterized by polymicrobial infections. The mortality rates about 7% is the privilege of diffuses forms. The treatment associates medical and surgical procedures, and consists in polyantibiotherapy and excision of suppurative lesions. From a series of 155 cases we analyse the pathogenical, clinical and therapeutical aspects. PMID- 1435188 TI - [Infectious endocarditis. Experience of a service in Brazzaville. 47 cases]. AB - The aim of this study was to report the authors' experience of infective endocarditis (IE) from 47 cases collected between 1976 to 1991. Infective endocarditis (IE) was documented with surgical (n = 9), microbiological (n = 26), and echocardiographic (n = 30) criteria. There were 11 male, 36 female: mean age, 26.2 +/- 10.3 years (extremes: 17 and 47). The authors noted a great importance of gynecological portal entry (13 cases), acute infective endocarditis (23 cases i.e. 48.9%), heart failure (39 cases i.e. 82.9%), and pulmonary (4 cases i.e. 8.5%) and systemic (8 cases i.e. 17.0% embolism. Surgical treatment was impossible in Brazzaville. Trans-thoracic echocardiography was performed in 38 cases and revealed vegetations in 30 cases i.e. 78.9%. Twenty patients died (42.5%) because heart failure. There was no significant difference in letality between infective endocarditis treated surgically or no, between native valve or prosthetic valve infective endocarditis, between culture negative or culture positive infective endocarditis (IE). This study corroborate that infective endocarditis is a heavy illness, characterized by high frequency of heart failure. The authors insist upon the prevention of infective endocarditis. PMID- 1435189 TI - [Measles control in the 1990s: perspectives of prevention and eradication with special reference to Africa]. AB - A discussion of knowledge gained on measles during the 1980s leads to an outline of research priorities for the 1990s. Special emphasis is laid on the vaccine schedule, with particular emphasis on two dose schedules, on virus dissemination from town to country, and on two pronged strategies for town and country. PMID- 1435190 TI - [Scleroma and rhinoscleroma]. AB - Scleroma is a specific granulomatous disease of bacterial origin, chronic evolution, with election in respiratory tracts; nose lesion is practically constant and so justifies the term Rhinoscleroma. Although they are many endemic foci throughout the world and in particular in Africa, it is an uncommon disease, often not recognized for polymorphic. The cases recorded out of already known foci concerned generally migrants; autochtonous cases in France are really infrequent. Within the evolutive lesions diagnosis is made out of the isolation of the responsible germ (Klebsiella rhinoscleromatis) and the presence of the specific Mikulicz' cell. To find out localizations in the same patient, we utilize X Rays and endoscopy. Antibiotic therapy is of long duration but treats the affection and prepares the way of surgery intervention to eliminate cicatricial deformities. Relapses are caused by shortness of therapy and some difficulty to monitor patients. Mortel in the past, scleroma should nowadays, be better recognized to be better treated and cured. PMID- 1435191 TI - [A new case report of omphalocele in a newborn (Kamenge University Hospital Center at Bujumbura, Burundi)]. AB - A new case report of new born baby's omphalocele allows us to precise the embryological data indispensable to understand the genesis of this pathology. The future of the primitive intestinal loop and the explanation of the temporary physiological hernia, are the basis of such phenomenons rarely reported and they complete the three cases' report recently published. PMID- 1435192 TI - [Mycobacterium fortuitum in a patient with human immunodeficiency syndrome (AIDS) in Benin)]. AB - The authors report a case of Mycobacterium Fortuitum infection in one AIDS patient. This case underlines the interest for the clinicians to investigate systematically a possible infection by Mycobacterium fortuitum in all AIDS patients with pulmonary tuberculosis. PMID- 1435193 TI - [Evaluation of an indirect hemagglutination test for the serodiagnosis of amebiasis]. AB - 167 sera have been tested to appreciate the value of an indirect hemagglutination test (Amibiase HAI FUMOUZE) comparatively to an agglutination test of sensibilized particles of latex (Bichro latex Amibe Fumouze BLA) Amibiase HAI test comes out as sensitive and specific for the detection of antibodies in patients suffering from visceral amoebiasis. But some antibodies are also detected in patients with an antecedent of amoebiasis, as it is usually the case with some other techniques. A high positivity of the indirect hemagglutination test, and the concordance between the test HAI and the BLA one are in favour of a visceral amoebiasis. While lower rates or discrepancy between the two tests may evoke an hidden infestation in patients coming out or originated from endemic zones. PMID- 1435194 TI - [Variation of the parasite density of Plasmodium falciparum in asymptomatic carriers: consequences for malaria chemoresistance studies]. AB - During the studies on malaria chemoresistance, we noted great variations in parasite density of Plasmodium falciparum between screening in the morning and final selection in the afternoon, in asymptomatic people. To better understand this phenomenon, we conducted a study in october 1987 on primary school children in a village near the city of Bobo-Dioulasso, at the peak malaria prevalence. We performed 3 blood-smears at 8 a.m., 2 p.m. and 8 p.m., on Day 0 and Day 4, to an initial number of 86 children, aged from 6 to 9 years. By the end of the study 44 children remained who fulfilled the inclusion criteria Among them 35 showed a parasitaemia on Day 0 and 9 remained negative. On Day 4, 28 were positive and 16 remained negative. Of the 35 children positive at entry to the study 16 remained continuously positive, the others were negative on at least one occasion. Of the 28 children positive on Day 4, 14 remained continuously positive. For the 16 people with a parasitaemia continuously positive on Day 0.7 (43.7 p. cent) became spontaneously negative on Day 4. But considering the small size of our sample, the analysis of the nycthemeral variation and of the variation between the two days did not show a significant difference. Further studies involving a greater number of blood-smears during a longer period and concerning more people, should be conducted. The possibility of spontaneous negativation of the parasitaemia without drug absorption shows that there are some cases of false malaria chemosensitivity that are declared when the in vivo tests are not coupled with in vitro tests. PMID- 1435195 TI - [Bibliographic notes. Medicine and tropical specialties]. PMID- 1435196 TI - Effect of lithium on the double-quantum behavior of 23Na in normal human erythrocytes. AB - The double-quantum behavior of 23Na in the presence of different concentrations of Li in human erythrocytes was investigated. The 23Na double-quantum signal was quenched in both the extracellular and the intracellular compartments with increasing concentration of Li in each compartment, along with an increase in the 23Na T1 both intra- and extracellularly. Some extracellular quenching could be observed at the near therapeutic concentration of 2 mM Li. The ratio of slow to fast spin-spin (T2) relaxation times, obtained from the dependence of the double quantum signal on creation time, approached unity at an overall Li concentration of 40 mM. These results provide evidence that Li and Na compete for both intra- and extracellular binding sites in erythrocytes. PMID- 1435197 TI - A novel method for fat suppression in RARE sequences. AB - Rapid acquisition relaxation-enhanced (RARE) sequences (Hennig et al., Magn. Reson. Med. 3, 823 (1986)) utilize one or several Carr-Purcell-Meiboom-Gill (CPMG) echo trains to sample a number of k-space lines each repetition time TR. The technique can rapidly generate multislice T2-weighted images which, as a rule, are strikingly similar in contrast to conventional T2-weighted spin-echo (SE) images. An exception to this rule is the appearance of very bright signal from fat in T2-weighted RARE images as compared to conventional T2-weighted SE images. To reduce this fat signal, we introduce a time delay, tau c, between the 90 degrees x and first 180 degrees y pulse of each echo train such that a phase angle of pi/2 develops between fat and the reference (water) line at echo maxima. The technique leads to single-acquisition fat suppression without the use of frequency-selective saturation pulses and concomitant loss of slices per TR. A Bloch equation analysis is used to identify two major mechanisms contributing to suppression of off-resonance spins such that w tau c = pi/2. Namely, the CPMG sequence becomes a CP sequence with no self-correction properties for imperfect 180 degrees pulses leading to enhanced signal decay, and the raw k-space data matrix become segmented into blocks alternately multiplied by +/- i, leading to signal dispersion following Fourier transformation. PMID- 1435198 TI - Validation of 13C NMR measurement of human skeletal muscle glycogen by direct biochemical assay of needle biopsy samples. AB - Recent developments in 13C nuclear magnetic resonance (NMR) spectroscopy have permitted noninvasive assessment of glycogen concentration in human skeletal muscle. Before these indirect measurements could be accepted as accurate, it was essential that validation should be carried out by comparing the widely used method of muscle biopsy and direct biochemical assay for glycogen concentration with measurement by NMR. Eight normal subjects underwent six NMR scans of gastrocnemius and three biopsies of the same muscle on the same day. The overall mean for muscle glycogen concentration was 87.4 mM by NMR and 88.3 mM by biopsy. There was a close correlation between the pairs of observations on each subject (R = 0.95; P less than 0.0001). The mean coefficient of variation for NMR measurement was 4.3 +/- 2.1% and that for biopsy was 9.3 +/- 5.9%. The performance of the muscle biopsies was accompanied by a small but significant rise in plasma-free fatty acids (529 +/- 157 to 667 +/- 250; P less than 0.01), epinephrine (17 +/- 6 to 25 +/- 8 pg/ml; P less than 0.02), and norepinephrine (318 +/- 119 to 400 +/- 140 pg/ml; P less than 0.02) but no change in plasma glucose, plasma insulin, nor muscle glycogen concentration assessed by NMR. The study demonstrates that in vivo 13C NMR measurement of human muscle glycogen can be regarded as accurate, and the technique is associated with a higher precision that biopsy with direct biochemical assessment. PMID- 1435199 TI - Charge dependence of the distribution of contrast agents in rat cerebral ventricles. AB - Previous studies of MRI contrast resulting from the intracerebral administration of several contrast agents have suggested that the distribution of these agents may be dependent on the net charge. In order to further evaluate the significance of this parameter, the distribution of both aquo and CDTA-chelated lanthanide and transition metal ions in the cerebral ventricles of rats has been evaluated based on their enhancement of MRI contrast. The agents were injected directly into the lateral ventricles of Sprague-Dawley rats. Each of five different positively charged paramagnetic metal ions tested selectively enhanced the inner cellular layers of ventricular luminal wall of the rat brain, while such enhancement was absent using the corresponding negatively charged metal-CDTA complexes. The abundance of negatively charged residues on the cell surface of the inner luminal layers is suggested to be the source of the observed charge affinity. Differences in the distribution of Mn2+ ions administered intracerebrally compared with intraperitoneal (ip) injection suggest that while the first treatment may result primarily in uncomplexed aquo ions which then interact with the luminal surface, manganese ions administered ip behave more like chelated ions and are most probably complexed to transferrin. PMID- 1435200 TI - On the application of ultra-fast RARE experiments. AB - The ultra-fast application of the RARE experiment is described in detail, with special emphasis on its multifarious applications with preparation experiments that produce transverse magnetization. The factors affecting the temporal evolution of the magnetization during the experiment are described, and the implications for the slice profile when using a Gaussian refocusing pulse are experimentally examined. The choice of phase-encoding scheme for use with preparation experiments is discussed, as is the use of various phase-encoding schemes to reduce line broadening in the phase-encoding direction if a number of averages are acquired. An explanation for the decomposition of the echo are into two components if the read gradient is imbalanced is given, and the experimental conditions necessary for the coherent addition of these two echo groups are described. An alternative sequence that removes one of these groups from the acquisition window is proposed. The sensitivity of the sequence to flow and motion is investigated, and the drastic loss of signal in this situation explained. The in vivo and in vitro application of preparation experiments leading to the accurate measurement of T1, T2, diffusion constant, and magnetization transfer characteristics is presented. The implementation of zoom imaging using spin- and stimulated-echo preparation is described, and 3D in vivo spin-echo zoom images are presented. Simple phantom experiments demonstrating the feasibility of chemical-shift selective and spectroscopic imaging are also given. PMID- 1435201 TI - Breast coil design for low-field MRI. AB - Four double-breast coils were designed for the low-field resistive magnet MR imaging of female breasts at 0.02, 0.04, and 0.1 T. The signal-to-noise ratio is optimized by shaping the coils, by constructing two different size coils at 0.02 T, and by using special wire for the turns of the solenoidal coils. The approximate linear dependence of the SNR on the Larmor frequency is estimated. PMID- 1435202 TI - The capillary network: a link between IVIM and classical perfusion. AB - MR measurements based on motion encoding gradients, such as intravoxel incoherent motion imaging, could provide, in principle, information on flowing blood volume and blood velocity. This note shows that, in addition, the knowledge of the capillary network organization may provide a link between these measurements and those obtained by conventional and MR perfusion techniques based on tracer uptake by tissues. PMID- 1435203 TI - T1 values of phosphomonoester and phosphocreatine of brain show no significant change during development. AB - Changes in apparent 31P spin-lattice relaxation times (T1) associated with brain development were investigated in rat pups. While analysis of variance showed strong age dependency in [PME]/[ATP] and [PCr]/[ATP], the T1 values of PME, PCr, and ATP did not show any age dependency. The studies indicate that in contrast to the data which indicated aging-related changes in the T1 values of PME, the observed changes in PME during neonatal development are likely to be quantitative in nature. PMID- 1435204 TI - Detection and assignment of the glucose signal in 1H NMR difference spectra of the human brain. AB - The difference between 1H NMR spectra obtained during eu- and hyperglycemia exhibited well-resolved glucose peaks between 3 and 4 ppm as demonstrated by comparison with solution spectra. Estimated increases were consistent with recent 13C NMR quantitations of intracerebral glucose. Difference spectra were measured in 36-ml volumes from the human brain every 3 min. PMID- 1435205 TI - Evaluation of experimental early acute cerebral ischemia before the development of edema: use of dynamic, contrast-enhanced and diffusion-weighted MR scanning. AB - The ability of dynamic, contrast-enhanced, magnetic susceptibility-weighted scanning to delineate early experimental acute cerebral infarction was compared with that of heavily T2-weighted and diffusion-weighted spin echo scanning. Spontaneously hypertensive rats, which had undergone right middle cerebral artery occlusion, were studied from 15 min to 3 h post ligation on a 1.5-T clinical whole-body imager. In contrast to the diffusion- and T2-weighted spin echo scans, the dynamic, contrast-enhanced technique clearly and consistently delineated the nonperfused regions as early as 15 min post ligation. PMID- 1435206 TI - Monitoring the progression of spermatogenesis by 31P magnetic resonance spectroscopy. PMID- 1435207 TI - A nuclear magnetic resonance investigation of the upper airways in ferrets. I. Effects of histamine and methacholine. AB - Alterations induced in the upper airways of ferrets by intranasal provocation with methacholine (MC) and histamine (HS) were monitored using proton magnetic resonance imaging (MRI) and spin-spin relaxation rate (R2) measurements. Both MC and HS cause a significant increase in the MRI signal intensity and a decrease in R2 in the nasal turbinates. A dose-dependent response is observed for 20 to 315 nmol of HS, with a maximum increase in intensity of ca. 50% occurring above 80 nmol. A single unilateral challenge with MC yields a 62 +/- 3% increase in intensity. Control animals (saline-treated) show little change in image intensity. MC and HS cause decreases in the proton R2 by -27.0 +/- 5.5% and -17.2 +/- 4.3%, respectively. These data are indicative of an accumulation of fluid in the nasal airways. MRI provides an effective means to monitor changes in the nasal airways which occur as a result of pharmacological treatment. PMID- 1435208 TI - A nuclear magnetic resonance investigation of the upper airways in ferrets. II. Contrast-enhanced imaging to distinguish vascular from other nasal fluids. AB - Proton magnetic resonance imaging (MRI), used in conjunction with the intravascular contrast agent albumin-(Gd-DTPA), provides a means to distinguish vascular fluids from other nasal fluids in the upper airways. Ferrets were given an intravenous dose of albumin-(Gd-DTPA) followed by an intranasal challenge with either histamine (HS) or methacholine (MC). An observed increase in image intensity indicates that HS and MC both cause an accumulation of fluids in the nasal turbinate region. The MRI data are also influenced by the presence of blood, which contains the contrast agent, and a clear distinction can be made between vascular fluids and other nasal fluids (i.e., cellular and glandular secretions). The results show that HS causes an increase in vascular fluids in the nasal turbinates while MC does not. This methodology represents a new means to investigate airway pharmacology and the pathophysiology associated with various pharmacological agents, allergens, or viral infections. PMID- 1435209 TI - The design of liposomal paramagnetic MR agents: effect of vesicle size upon the relaxivity of surface-incorporated lipophilic chelates. AB - The 1/T1 NMRD profiles of lipid vesicles with the paramagnetic ion Gd attached via a chelate covalently linked to the membrane surface show a peak at approximately 20 MHz indicating that fluctuations of approximately 10(-8) s contribute to the form of the dispersion profile. If the correlation time for fluctuations of the paramagnetic chelate on the membrane surface is much less than the correlation time for rotation of the lipid vesicle, it would be expected that the measured 1/T1 relaxation rate for solvent protons should be invariant with vesicle size above a certain minimum vesicle diameter. We show that this is indeed the case for vesicles in the size range 50 to 400 nm average diameter and discuss general design considerations for the preparation of vesicle-associated MR contrast agents based upon paramagnetic chelates either trapped within the vesicle interior or attached to the membrane surface. PMID- 1435210 TI - Magnetic resonance imaging of myocardial kinematics. Technique to detect, localize, and quantify the strain rates of the active human myocardium. AB - A magnetic resonance imaging (MRI) method is presented to detect, localize, and quantify myocardial kinematics by measuring the material rate-of-strain tensor at each pixel in gated NMR images of the heart. The immediate, local effect of muscular activity is self-deformation, and the strain tensor is the basic mathematical device by which such deformation may be quantified. The present method, called "strain-phase" MRI (SP-MRI), entails four steps: (1) the velocity of the myocardium is encoded by means of a set of motion-sensitive NMR image acquisitions, one image per velocity component; (2) the spatial derivatives of the velocity are computed at each pixel; (3) the velocity-derivative data are combined to compute an approximation of the strain-rate tensor of the myocardium at each pixel; and (4) the strain-rate tensor data are simplified to produce a color-coded functional image which represents strain-rate components which are of particular biomedical interest in the myocardium. We present a quantitative SP MRI methodology suited to conventional MRI, and in addition present an "echo planar" methodology, able to produce qualitative functional images of myocardial kinematics at almost real-time speeds. Two-dimensional strain-phase MRI data acquired in normal human subjects are presented. These data demonstrate the practicability of SP-MRI in vivo, that SP-MRI resolves myocardial kinematics at the single-pixel scale, having resolution comparable to that of conventional MRI, and that SP-MRI data may have a signal-to-noise ratio up to 50% as great as that of the conventional MRI data from which they are produced. SP-MRI measurements of the local instantaneous strain rates in the human left ventricular myocardium are quantitatively consistent with known transmural average values of myocardial strain. PMID- 1435211 TI - Measurement of blood-brain barrier permeability in a tumor model using magnetic resonance imaging with gadolinium-DTPA. AB - Sequential MR imaging with gadolinium-diethylenetriaminepentaacetic acid (Gd DTPA) and sequential measurements of plasma Gd-DTPA concentration by inductively coupled plasma atomic emission spectroscopy (ICP-AES) were used to estimate the blood-to-tissue transport coefficient (Ki) in the 36B-10 rat glioma model. For these measurements, tissue Gd-DTPA concentration was estimated from tumor enhancement by correlation with calibration measurements obtained by ICP-AES analysis of tumor tissue. The 14 animals for which Ki was calculated can be grouped into those imaged at 11 days following tumor implantation, at 13-18 days, and at 20 days. The mean (+SEM) Ki values for these groups were 1.1 + 0.24, 9.2 + 0.8, and 13.4 + 1.7 ml/kg-min, respectively. These results correspond well with published data obtained by quantitative autoradiography. It is concluded that frequent sequential imaging and a graphical approach to Ki calculation are promising methods for determining the blood-to-tissue transport coefficient noninvasively by contrast-enhanced MRI. PMID- 1435212 TI - Determination of concentrations by time domain fitting of proton NMR echo signals using prior knowledge. AB - A fast and flexible time domain iterative fitting procedure that can be used to fit free induction decays as well as echo-like signals is described. Damping constants of the first and second part of the echo do not have to be identical. Prior knowledge can be used to diminish the number of parameters to be fitted, which results in an improved accuracy. It is shown how prior knowledge is mathematically incorporated in the Gauss-Newton method. From proton NMR measurements of model solutions actual prior knowledge is extracted. With this knowledge relative concentrations are determined from a mixture of metabolites. The fitted results agree with the true values within the margins of the noise. After some minor changes the same prior knowledge was successfully used to analyze a series of in vivo rat brain measurements. PMID- 1435213 TI - Relationship between the degree of unsaturation of dietary fatty acids and adipose tissue fatty acids assessed by natural-abundance 13C magnetic resonance spectroscopy in man. AB - Natural-abundance 13C magnetic resonance spectroscopy was used for determining noninvasively the relative concentration of mono- and polyunsaturated fatty acids of adipose tissue in two groups of volunteers. The first consisted of subjects who had followed a fat-reduced diet for at least half a year before the 13C measurements. The second were control subjects who were on a usual high-fat diet. The ratio of unsaturated to total fatty acids in adipose tissue determined by 13C MRS correlated significantly with the same ratio in fat of the diet composition estimated by a dietician according to food records. The results indicate that 13C MRS is capable of assessing the degree of unsaturation of dietary fatty acids consumed during the preceding months. PMID- 1435214 TI - Determination of absolute phosphate metabolite concentrations in RIF-1 tumors in vivo by 31P-1H-2H NMR spectroscopy using water as an internal intensity reference. AB - The absolute metabolite quantification method of Thulborn and Ackerman [J. Magn. Reson. 55, 357 (1983)] in which the tissue water proton signal is used as an internal intensity standard and its more recent variation in which NMR peak intensities are referenced to that of the natural abundance deuterium signal of water [Li et al., SMRM Abstr. 2, 825 (1988); Song et al., Magn. Reson. Med. 25, 45 (1992) have been implemented to obtain absolute phosphate metabolite concentrations in subcutaneous RIF-1 tumors during untreated growth and following treatment with 5-fluorouracil. The equivalence of these two hydrogen isotopes as intensity standards and the validity of their use in the determination of absolute metabolite concentrations in vivo by NMR has been demonstrated. On matched in vivo and extract tumor samples (n = 5), excellent agreement has been obtained between nucleoside triphosphate concentrations determined by NMR and those derived by HPLC analysis for the control tumors. Following 3 days of untreated growth, absolute concentrations of phosphate metabolites in RIF-1 tumors (n = 10) decreased significantly, except for the Pi concentration which did not vary. For the treated tumors (n = 10) there were no changes in metabolite concentrations except for a decrease in the PCr and, possibly, Pi concentrations. The PCr/Pi ratio in the latter tumors did not change. These observations suggest that changes in absolute metabolite concentrations may be more sensitive indices of response to therapy than changes in metabolite peak amplitude ratios, a parameter commonly used to express in vivo NMR data. PMID- 1435215 TI - Phasing spin-echo-acquired 31P spectroscopic images using complex conjugate data reversal. AB - A simple method has been developed for phasing 31P spectroscopic images acquired with short echo-time (1-2 ms) spin-echo sequences. The technique is based on reconstructing complete echoes in the time domain by the reversal of the complex conjugate of the data. After Fourier analysis, a magnitude reconstruction is used, which no longer broadens the lines. Advantages of the method compared to other phasing procedures are discussed. PMID- 1435216 TI - Feasibility of 19F imaging of perfluorochemical emulsions to measure myocardial vascular volume. AB - 19F magnetic resonance images were obtained of the ventricular walls of isolated rabbit hearts perfused with a perfluorochemical (PFC) emulsion. Since the PFC is known to stay within the vascular space in normal myocardial tissue, the 19F signal should reflect myocardial vascular volume. 19F MRI of PFC emulsions represents a new investigational tool for the study of coronary vascular volume. PMID- 1435217 TI - 13C and 1H NMR study of the metabolic degradation of 4-pentenoate in different dog nephron segments. AB - The metabolism of 4-pentenoate in isolated kidney tubules has been investigated by 1H and 13C NMR. The 4-pentenoate metabolite, 3-keto-4-pentenoyl-CoA, accumulated in proximal tubules only and its formation could be competitively inhibited by octanoate. 4-Pentenoate was metabolized in thick ascending limbs but not in papillary collecting ducts. PMID- 1435218 TI - Use of fluid-attenuated inversion-recovery pulse sequences for imaging the spinal cord. AB - Fourteen patients with disease of the spinal cord were imaged with fluid attenuated inversion-recovery (FLAIR) sequences in which the inversion time was chosen to substantially reduce or null the signal from CSF. Lesions were seen with greater conspicuity than with conventional contrast-enhanced and -unenhanced T1- and T2-weighted sequences in 11 cases. PMID- 1435219 TI - NMR venography using the susceptibility effect produced by deoxyhemoglobin. AB - A new angiography technique using the susceptibility effect is proposed. Blood containing deoxyhemoglobin is more paramagnetic than surrounding tissue and thereby produces a susceptibility effect at blood-tissue interfaces. By use of a specially tailored RF pulse, signals from normal tissues are suppressed while the signals from blood interfaces, where strong susceptibility-induced fields are created, are enhanced. The design and characteristic behavior of the tailored RF pulse are discussed and experimental results obtained using both a phantom and a human volunteer with a 2.0-T whole-body NMR system are also presented. PMID- 1435221 TI - An NMR phased array for human cardiac 31P spectroscopy. AB - A four-coil phased-array 31P NMR receiver was designed and tested for human cardiac applications, to determine whether the combination of relatively high signal-to-noise ratio (SNR) and large field of view produced in 1H imaging is also realized for in vivo 31P spectroscopy. Spectra were acquired in parallel from an array of four overlapping 6.5-cm surface coils using one- and two dimensional phase-encoding pulse sequences and were optimally combined to yield composite spectroscopic images. The phased array was found to generate useful 31P spectra from a 2.5-fold wider lateral region around the anterior myocardium than a single receiver of the same size as the array elements, with no increase in imaging time. In addition, the sensitive depth was increased by up to 2 cm over that of a single coil. Spectra could be acquired in roughly 15 min from a region extending to the middle of the heart, with voxel sizes of 2 x 2 x 4 cm3. For the average heart voxel, the SNR of the combined spectrum was higher than that of the best spectrum from any one coil in the array by 30%, with some voxels showing an increase as high as 60%. PMID- 1435220 TI - Atraumatic quantitation of cerebral perfusion in cats by 19F magnetic resonance imaging. AB - We have noninvasively produced low-resolution, quantitative nuclear magnetic resonance images of cerebral blood flow in 2-ml voxels in eight cats. Typical signal-to-noise of 4 to 1 was obtained in cerebral voxels in 16.5-s epochs. Mean flow during normocapnia (paCO2 = 39 +/- 4 mm Hg) and hypercapnia (paCO2 = 62 +/- 4 mm Hg) was 53 +/- 20 ml/100 g-min and 140 +/- 36 ml/100 g-min, respectively. Fast flows in normocapnia were 94 +/- 13 and 182 +/- 39 ml/100 g-min in hypercapnia. These results suggest that an atraumatic quantitative imaging assessment of cerebral perfusion may be possible in humans using these techniques. PMID- 1435222 TI - Glycogen detection by in vivo 13C NMR: a comparison of proton decoupling and polarization transfer. AB - The performance of gated proton decoupling and polarization transfer with respect to glycogen detection by 13C NMR was investigated. Experiments were performed on a 1.5-T whole-body scanner using a 13C surface coil in combination with a proton head coil. Spectra were acquired from a glycogen phantom and from the lower leg of a healthy volunteer using proton decoupling and the polarization transfer method SINEPT. The signal strength of the C1 resonance of glycogen was determined and compared to a reference spectrum acquired without any form of sensitivity enhancement. In the phantom experiment both decoupling and SINEPT produced a signal gain of 3.5. Under in vivo conditions, the signal gain was approximately 2.5 for both techniques. We conclude that decoupling and polarization transfer are equivalently useful techniques for glycogen detection. PMID- 1435224 TI - Quantitative MRI of the prostate and uterus in monkeys. AB - Quantitative MRI has been carried out in the prostate, seminal vesicles, uterus, and ovaries in the pig-tailed monkey, Macaca nemestrina. T2-weighted, fat suppressed, multislice experiments were performed at 2.35 T. Eight males, 14 ovariectomized females, and 20 intact females were studied. In the prostate, the caudal and cranial lobe were readily distinguished since the latter had a longer T2 value. For all tissues and organs, interanimal variations were large (up to 12 fold variation in volume), but reproducibility was excellent in the prostate and in the ovariectomized monkey uterus with coefficients of variation (CV) of 3 and 5%, respectively. In the intact monkey uterus, cycle-cycle reproducibility was good with CVs of 6-10% in the myometrium and 14-18% in the endometrium. In the follicular phase, endometrial growth (+3.8% day-1, P < 0.001) was accompanied by myometrial shrinkage (-1.6% day-1, P < 0.001), while in the luteal phase, growth was seen in both tissues (+4.3% day-1, P < 0.001 and +1.4% day-1, P < 0.001, respectively). The great value of these MRI techniques in obtaining data in pharmacological efficacy studies of endocrine drugs, and in limiting the number of animals used, is discussed. PMID- 1435223 TI - Simultaneous MR acquisition of arterial and brain signal-time curves. AB - Regional cerebral blood flow (rCBF) provides important information about local neuronal functional and cerebrovascular status. Determination of rCBF requires sequential measurements of tracer concentration in arterial blood and brain tissue unless the tracer is trapped in the brain in proportion to rCBF. Since gadopentate dimeglumine is not trapped within brain tissue, we have developed the simultaneous dual FLASH pulse sequence (SDFLASH) which sequentially measures the MR signal change in both the internal carotid artery and brain parenchyma simultaneously during the passage of a bolus of paramagnetic contrast material. PMID- 1435225 TI - The loss of small objects in variable TE imaging: implications for FSE, RARE, and EPI. AB - The importance to MR image quality of the order of acquisition of different phase encoded views with sequences that have variable TR and TE has been recently reported. It has been shown that the effective point spread function (PSF) may be manipulated by varying TE or TR, or both, with each phase-encoding step. This paper explores the behavior of the PSF in a variable TE sequence and its dependence on both imaging and tissue parameters. It is shown that the PSF is different for each tissue type and that its effect on tissue contrast is a function of both the shape and size of the structure. The important problem of signal loss from small objects that arises when the effective PSF is broad and the difficulty in detecting this phenomenon in practical MR images is illustrated. It is shown that the PSF can produce significant blurring and loss of object contrast in fast spin-echo images but that this blurring may be not be obvious in practice because the noise is unaffected by the PSF. It is also shown that the signal from small lesions with short T2 can easily be lost through this blurring mechanism. The importance of signal loss from small objects and its implication for the clinical use of such sequences as fast spin-echo or rapid acquisition relaxation-enhanced and echo planar imaging is stressed. PMID- 1435226 TI - Direct observation of the magnetization exchange dynamics responsible for magnetization transfer contrast in human cartilage in vitro. AB - Saturating irradiation far off-resonance can lead to diminution in the water signal seen in MRI, giving rise to magnetization transfer contrast. This results from transfer of magnetization between "solid" protons with restricted motion, which give rise to a band some tens of kilohertz wide, and the narrow signal from mobile protons. In the work reported here a high-power pulse spectrometer, which can detect signals from both mobile and immobile protons, was used to investigate the dynamics of magnetization transfer in cartilage in vitro. Magnetization transfer in modified Hoffman-Forsen inversion transfer experiments was well described by a single rate constant model; full analytical solutions are offered for the resultant biexponential magnetization recovery curves. The use of pulsed methods to generate magnetization contrast may in some circumstances offer advantages over the steady-state saturation methods used hitherto. PMID- 1435227 TI - Purification and characterisation of an extracellular metalloprotease, serine protease and haemolysin of Aeromonas hydrophila strain B32: all are lethal for fish. AB - Three different lethal (for rainbow trout, Salmo gairdneri) extracellular toxins were purified by HPLC from the culture supernatants of Aeromonas hydrophila strain B32 which had been isolated from rainbow trout. A metalloprotease, MW 38 kDa, was stable at 56 degrees C for 10 min, had no cytotoxic activity and and LD50 of 150 ng/g fish. In narrow range isoelectric-focusing (IEF) the enzyme had 11 isomers with (pls) between 4.12 and 4.8. A serine protease (22 kDa) was stable at 56 degrees C for 10 min, possessed cytotoxic activity and had an LD50 of 150 ng/g fish. In IEF, multiple isomers possessed pls between 4.5-5.2. The haemolysin had alpha-haemolytic activity (68 kDa) multiple isomers in IEF with pl range 4.5 5.1 and an LD50 of 2 micrograms/g fish. It was stable after heating to 56 degrees C for 20 min, 60 degrees C for 10 min and possessed esterase activity on beta naphthyl acetate. These latter properties suggest it may be a novel haemolysin distinct from alpha- and beta-haemolysin. PMID- 1435228 TI - The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl. AB - The clinical and laboratory features of 32 patients with anti-PM-Scl were studied. Patients with this rare autoantibody suffered from a homogenous overlap connective tissue disease defined by Raynaud phenomenon (32/32), features of scleroderma (31/32), arthritis (31/32, erosive in 9/32), myositis (28/32), lung restriction (25/32), calcinosis (15/32), and sicca (11/32). Significant renal and neurologic involvement was uncommon. All patients examined (22/22) had HLA-DR3, and 50% of these patients were homozygous. Our patients responded favorably to moderate immunosuppression and, with therapy, the disease generally has a good prognosis; over 50% of our series (17/32) remained well on minimal or no immunosuppression after a median follow-up of 8 years. PMID- 1435229 TI - Gaucher disease. Clinical, laboratory, radiologic, and genetic features of 53 patients. AB - We have reviewed our experiences with the clinical, laboratory, radiologic, and genetic features of 53 patients with Gaucher disease. Most were evaluated during early adult life, with a mean age of 33 years. Our patients were evaluated in a referral center, and therefore the data need to be interpreted with caution when applied to the general patient population, which includes a greater proportion of very mild cases. Thirty-nine patients were Ashkenazi Jews, 13 were non-Jewish and 1 was half-Jewish. The most common presenting symptom was bleeding related to splenomegaly and thrombocytopenia. The chronic symptoms, evaluated an average of 20 years after the diagnosis had been established, were mainly skeletal. Splenectomy had been performed in 43% of our patients and there was no evidence that this procedure accelerated the progression of liver and bone involvement. DNA from the patients was examined for 20 different mutations. The association between the 1226G/1226G genotype and a milder clinical course, and between the 1226G/84GG and 1226/1448C genotypes with more severe clinical manifestations, was confirmed. Repeated follow-up examinations in 29 patients revealed that in the majority of the patients, progression of the disease occurs during childhood, adolescence, or early adulthood with a marked tendency for stabilization thereafter. This observation suggests that Gaucher disease in most of the patients is not a relentless progressive disorder but a rather stable disorder during adulthood. The indications for the newly introduced intravenous enzyme replacement therapy as well as of future experimental treatments should be examined in the light of the natural history of the disease. PMID- 1435231 TI - Sjogren's syndrome. A clinical, pathological, and serological study of sixty-two cases. 1965. PMID- 1435230 TI - Spontaneous hemothorax. Report of 6 cases and review of the literature. AB - We present 6 cases of spontaneous hemothorax and comprehensively review the medical literature on this subject. We categorize the reported causes and offer a rational diagnostic approach to patients with nontraumatic hemothorax. We recommend specific treatments for specific etiologies, and emphasize the importance of well-established surgical principles for the treatment of hemothorax. Our suggestions should enable physicians to accurately diagnose and expeditiously treat patients with spontaneous hemothorax. PMID- 1435232 TI - Mysticete (baleen whale) relationships based upon the sequence of the common cetacean DNA satellite. AB - The genomes of all extant cetaceans are characterized by the presence of the so called common cetacean DNA satellite. In the mysticetes (whalebone whales) the repeat length of the satellite is 1,760 bp. In the odontocetes (toothed whales), other than the family Delphinidae, the repeat length is usually approximately 1,740 bp. The Delphinidae are characterized by a repeat length of approximately 1,580 bp. It has been shown in odontocetes that the satellite evolves in concert and that differences between species, with respect to the sequence of the satellite, correspond reasonably well to their evolutionary distances. In the present study the sequence of the satellite was determined in three repeats in each of seven mysticete species, and a consensus for each species established. Parsimony and neighbor-joining analyses based upon sequences of all repeats showed that the primary evolutionary distinction among the mysticetes is between the Balaenidae sensu stricto (i.e., the bowhead whale and the right whale) and all remaining species, including the pygmy right whale, a species that usually has been included in the Balaenidae. The comparisons also showed that the humpback whale and the gray whale were approximately equidistant from the blue whale and the fin whale (genus Balaenoptera). Concerted evolution of the satellite was also demonstrated among the mysticetes, but it appeared to evolve more slowly in the mysticetes than in the odontocetes. PMID- 1435233 TI - Evolution of the expression of the Gld gene in the reproductive tract of Drosophila. AB - During the preadult development of Drosophila melanogaster, the GLD (glucose dehydrogenase) gene (Gld) is expressed in a variety of tissues, including the immature reproductive tract. At the adult stage the expression of Gld becomes largely restricted to the reproductive tract of males and females. We examined the expression of GLD in the adult reproductive tract of 50 species in the genus Drosophila, as well as in those of a few representative species from four other closely related genera. GLD exhibits considerable organ-specific diversity in the reproductive tract of males and females. Among these species, five male GLD phenotypes and six female GLD phenotypes were found. In contrast, the preadult expression of GLD in representative species from each distinct adult pattern type was determined and found to be highly conserved in both the immature reproductive tract and non-reproductive organs. Moreover, the set of reproductive organs that express GLD during preadult development is equivalent to the sum of the five male and six female adult GLD phenotypes. To initially define the contribution of cis- versus trans-acting factors responsible for differences in adult GLD expression between two of these species--D. melanogaster and D. pseudoobscura--we transferred the D. pseudoobscura Gld to the genome of D. melanogaster and investigated its expression. GLD expression patterns of these transformants displayed characteristics that are unique to both species, suggesting the presence of both cis- and trans-acting differences between these two species. PMID- 1435234 TI - Sequence evolution in mitochondrial ribosomal and ND-1 genes in lepidoptera: implications for phylogenetic analyses. AB - A 2,256-bp sequence of the mitochondrial genome of a lepidopteran (Spodoptera frugiperda) contains tRNAs for valine and leucine, the 16S rRNA, and three quarters of the ND-1 presumptive protein-coding gene. A 64-bp stretch of unknown function was located between the rRNA and leucine tRNA. Sequence divergence in the 16S rRNA obtained from alignment with published insect sequences is consistent with phylogenetic hypotheses, in that Diptera and Lepidoptera are more closely related to each other (24% sequence divergence) than either is to Hymenoptera (31%). Within the ND-1 gene, sequences for four additional Lepidoptera were generated for a 314-bp region and contrasted with published sequences for the locust and Drosophila. Sequence divergence in this region was consistent with accepted phylogenetic relationships, but results of parsimony analyses were not. Cladograms consistently recovered accepted higher level relationships (monophyly of Lepidoptera), despite high homoplasy, but were unable to resolve superfamily and family relationships within Lepidoptera, regardless of the outgroup or character subset analyzed. Character analysis indicated that homoplasy was decreased at higher levels when first- and second-codon sites were used exclusively. At the lowest level (families), resolution was enhanced by inclusion of third-codon sites. Inability of molecular data to recover a well established phylogeny may be rectified by additional characters or taxa, but it is clear that homoplasy is sufficiently high to caution against the acceptance of relationships generated with this molecular region that are not extremely robust. PMID- 1435235 TI - Complete congruence between morphological and rbcL-based molecular phylogenies in birches and related species (Betulaceae). AB - Estimations of phylogenies from morphological and molecular data often show contrasting results. We compared morphological and molecular phylogenies in an ancient family of woody dicots, the Betulaceae (birch family). The phylogeny of the family was estimated from parsimony analysis of morphological characters in the genera Alnus, Betula, Carpinus, Corylus, Ostrya, and Ostryopsis and from parsimony and distance-matrix analyses of DNA sequences of the chloroplast gene encoding the large subunit of ribulose-1,5-biphosphate carboxylase (rbcL) in the genera Alnus, Betula, Carpinus, Corylus, and Ostrya and in two outgroups, Quercus and Liquidambar. The topologies obtained by the different methods were completely congruent, and bootstrapping strongly supported the division of the family Betulaceae into two major clades, Betuleae (Alnus and Betula) and Coryleae (other members). Only slightly more homoplasy was present in the rbcL sequence data set than in the morphological set. Relative-rate tests indicated that the Coryleae clade had a faster rate of rbcL evolution than did the Betuleae clade. Heterogeneity of rates of morphological evolution also paralleled those for rbcL. PMID- 1435236 TI - The 5S ribosomal RNA gene in Pythium species: two different genomic locations. AB - The 5S ribosomal RNA (rRNA) genes in eukaryotes may occur either interspersed with the other rRNA genes in the ribosomal DNA (rDNA) repeat, or in separate tandem arrays, or dispersed throughout the genome. In Pythium species and in several related Oomycetes, polymerase chain reaction (PCR) amplification of the nontranscribed spacer (NTS) region with one primer specific for the 5S gene revealed, with several exceptions, that the 5S rRNA gene was present in the rDNA repeat of those species with filamentous sporangia and was absent from the rDNA repeat of those with globose or unknown sporangia. When present, the gene was located approximately 1 kb downstream of the large-subunit rRNA gene and on the strand opposite that on which the other rRNA genes were located. This was confirmed in P. torulosum by sequencing of the gene and its flanking regions. The 5S rRNA genes of P. ultimum were found in tandem arrays outside the rDNA repeat. Evidence of dispersed 5S rRNA sequences was also observed. For many of the species of Pythium having the 5S gene in the NTS, the region between the large subunit rRNA gene and the 5S gene was found to have length heterogeneity. Oomycetes related to Pythium were also found to have the 5S gene in the NTS, although sometimes in the opposite orientation. This may mean that the presence of the gene in the NTS is ancestral for the Oomycetes and that the absence of the gene in the NTS in those Pythiums with globose sporangia is due to loss of the gene from the rDNA repeat in an ancestor of this group of species. These results favor the view that 5S rRNA gene linkage to the rRNA cistron existed prior to the unlinked arrangement seen in most plants and animals. PMID- 1435237 TI - Group I introns within the nuclear-encoded small-subunit rRNA gene of three green algae. AB - Four group I introns from the nuclear-encoded (18S) rRNA genes of three chlorophycean green algae are described; two are in Dunaliella parva, and one each is in D. salina and Characium saccatum. The introns within the gene in the latter two organisms are located at the sites equivalent to the 5' and 3' introns of D. parva, respectively. All four introns lack open reading frames and are relatively small, 381-447 bp. Both primary- and secondary-structural features place these introns within subgroup IC1 described by Michel and Westhof. Phylogenetic relationships of the three intron-containing taxa and their relatives, as inferred from comparisons of 18S rDNA sequences, suggest that inheritance of the introns along with the gene can account for their present distribution. The discovery of these four introns, in addition to two others known to exist in other chlorophycean green algae, suggests that group I introns within the 18S rRNA gene may be relatively common in the green algae. PMID- 1435238 TI - Statistical properties of bootstrap estimation of phylogenetic variability from nucleotide sequences. I. Four taxa with a molecular clock. AB - The statistical properties of sample estimation and bootstrap estimation of phylogenetic variability from a sample of nucleotide sequences are studied by using model trees of three taxa with an outgroup and by assuming a constant rate of nucleotide substitution. The maximum-parsimony method of tree reconstruction is used. An analytic formula is derived for estimating the sequence length that is required if P, the probability of obtaining the true tree from the sampled sequences, is to be equal to or higher than a given value. Bootstrap estimation is formulated as a two-step sampling procedure: (1) sampling of sequences from the evolutionary process and (2) resampling of the original sequence sample. The probability that a bootstrap resampling of an original sequence sample will support the true tree is found to depend on the model tree, the sequence length, and the probability that a randomly chosen nucleotide site is an informative site. When a trifurcating tree is used as the model tree, the probability that one of the three bifurcating trees will appear in > or = 95% of the bootstrap replicates is < 5%, even if the number of bootstrap replicates is only 50; therefore, the probability of accepting an erroneous tree as the true tree is < 5% if that tree appears in > or = 95% of the bootstrap replicates and if more than 50 bootstrap replications are conducted. However, if a particular bifurcating tree is observed in, say, < 75% of the bootstrap replicates, then it cannot be claimed to be better than the trifurcating tree even if > or = 1,000 bootstrap replications are conducted. When a bifurcating tree is used as the model tree, the bootstrap approach tends to overestimate P when the sequences are very short, but it tends to underestimate that probability when the sequences are long. Moreover, simulation results show that, if a tree is accepted as the true tree only if it has appeared in > or = 95% of the bootstrap replicates, then the probability of failing to accept any bifurcating tree can be as large as 58% even when P = 95%, i.e., even when 95% of the samples from the evolutionary process will support the true tree. Thus, if the rate-constancy assumption holds, bootstrapping is a conservative approach for estimating the reliability of an inferred phylogeny for four taxa. PMID- 1435239 TI - Freeing phylogenies from artifacts of alignment. AB - Widely used methods for phylogenetic inference, both those that require and those that produce alignments, share certain weaknesses. These weaknesses are discussed, and a method that lacks them is introduced. For each pair of sequences in the data set, the method utilizes both insertion-deletion and amino acid replacement information to estimate a pairwise evolutionary distance. It is also possible to allow regional heterogeneity of replacement rates. Because a likelihood framework is adopted, the standard deviation of each pairwise distance can be estimated. The distance matrix and standard error estimates are used to infer a phylogenetic tree. As an example, this method is used on 10 widely diverged sequences of the second largest RNA polymerase subunit. A pseudo bootstrap technique is devised to assess the validity of the inferred phylogenetic tree. PMID- 1435240 TI - The effect of unequal transversion rates on the accuracy of evolutionary parsimony. AB - Evolutionary parsimony is an easy-to-use method of phylogenetic inference that is based on nucleic acid sequences and that does not require the assumption that evolutionary processes in the various sites on the molecule are identical. It does, however, require a parameter constraint, known as the "balanced transversion" assumption. We show that the accuracy of the procedure is fairly insensitive to moderate violations of this assumption--and that the procedure thus is applicable under more general conditions than previously thought. PMID- 1435241 TI - Age of the common ancestor of human mitochondrial DNA. PMID- 1435242 TI - A collagenous sequence in a prokaryotic hyaluronidase. PMID- 1435243 TI - Error introduced by the infinite-site model. PMID- 1435244 TI - [Pseudoneurotic syndromes in copper mine workers]. AB - In 59 miners of mine front places and 50 workers who performed their work on the places situated outside of mine work places the neurological examination was carried out. The nervous over-excitability syndromes connected with suffering from disturbances of sleep, headache and over-excitement in 62% of mine front places miners and in 28% of the other workers were noted. The probable causes of the nervous over-excitability syndrome occurred in the miners of copper mine were discussed. PMID- 1435245 TI - [Evaluation of mental functions in workers exposed to metallic mercury, inorganic lead and carbon disulfide]. AB - The aim of the study was to determine the similarities and differences between the groups of dysfunctions detectable using psychologic tests in workers exposed to metallic mercury, inorganic lead and carbon disulfide. The study groups included male workers examined in the Clinic of Occupational Diseases of the Institute of Occupational Medicine in Lodz. The subjects were supposed to the chronically intoxicated with Hg (27 persons), Pb (40 persons) and CS2 (40 persons). A wide variety of tests was used to examine reference groups matched appropriately according to sex, age and level of education. The comparative analysis of results showed that the range and extend of a decrease in psychic functions depend on the type of a neurotoxic agent. The most serious disorders (frequently those of organic brain disease type) were found in subjects exposed to CS2. Exposure to metallic mercury resulted in functional disorders of the psychic sphere, while exposure to inorganic lead caused some minor functional changes. The results of the psychological examination of the subjects may be useful both for individual analysis and for screening. PMID- 1435246 TI - [Evaluation of the usefulness of enzyme tests for the diagnosis of the effects of various organic solvents in the conditions of occupational exposure]. AB - The aim of the study was to evaluate the suitability of enzymatic tests for estimating the effects of organic solvents upon the organisms of daily exposed workers. The analysis was undertaken in 572 workers exposed to such solvents as toluene, xylene, cresols and benzine. Periodical examination was carried out for the purposes of the study. The level of excreting organic solvents' metabolites in urine and serum enzymes' activity were determined. Also, the activity of alanine and aspartate aminotransferases and of plasmatic cholinesterase was determined. The results of the study support the necessity of applying the enzymatic tests as a basic method of evaluating the toxic activity of organic solvents. PMID- 1435247 TI - [Exposure to organic solvent vapors during production of lacquers for automobile painting]. AB - This study was aimed at the development and improvement of the methods for determining solvent vapours to estimate occupational exposure in paint and varnish shops. Gas chromatographic method and mass spectrometry (GC-MS) were applied respectively for quantitative determination and identification of toxic substances in the work-room air in plants manufacturing carbamide car paints and commonly used phthalic paints. Particular attention was paid to aromatic hydrocarbon components of farbasol: ethyltoluenes, propylbenzene, isopropylbenzene, mesitylene, hemimelitene, pseudocumene, diethylbenzenes and cymene. These hydrocarbons constitute about 95% of farbasol. At present, the evaluation of exposure in paint and varnish factories and in paint shops in Poland is insufficient because of the lack of TLV values for the above solvents, as well as inadequate methods of determination used in majority of laboratories. PMID- 1435248 TI - [Bibliographic and documentary activities in the fields of occupational medicine and toxicology]. AB - Great variety of world's medical literature demands elaborating specific bibliographic publications. The authors present a review of world's medical bibliographies with special stress put on occupational medicine and toxicology. The role of indexing languages in the preparation of bibliographies was emphasized. Also, the bibliographic publications edited at the Institute of Occupational Medicine in Lodz were presented. The usefulness of this literature for the specialists in toxicology and occupational medicine was discussed. PMID- 1435249 TI - [Principles of developing the register of chemical substances in Poland]. AB - The author present the principles for establishing the register of chemical substances in Poland. After considering different world's registers of chemical compound it was observed that the rules of creating this sort of register in the USA are most suitable for the Polish demands. It was suggested that the criterion of classifying a given substance to the register should be the chemical's content 100 kg. For the substances known as cancerogenic this threshold level is going to be 5 kg. Moreover, the principles and a schedule for preparing such a register are specified. One of the most important conditions that must be fulfilled in order to establish the register is applying the relevant legal regulations. PMID- 1435250 TI - [Etiopathogenetic factors of degenerative diseases of the spine and the effects of exertion and working conditions]. AB - The work was based on literature concerning the etiopathogenesis of spondylosis and on communications estimating the effects of work conditions upon generating or intensification of degenerative disease syndromes. Traumas, micro-traumas, excessive static and dynamic workload are very important etiopathogenetic factors. The most frequently analysed occupational hazards comprise exercise body position at work, type of the movements performed, exposure to vibration. According to most authors, work conditions and ways of performing a given job may be listed among the factors that affect degenerative changes of the spinal cord. PMID- 1435251 TI - [Asbestos substitutes and their biological action. I. Types, use, exposure and MPEL]. AB - Referring to literature, the authors present problems of exposure to asbestos, its production and MACs in Poland. In our country artificial mineral fibres are produced in seven plants employing about 2000 workers. These plants produce basalt wool, sag wool and glass fibres used in industrial and building insulating materials and in cement and mortar additives and as a free insulating material. Mean concentrations of total dust at the work-posts measured in 1986-1989 ranged between 1.06 mg/m3 and 3.10 mg/m3. Concentrations of respirable fibres ranged from 0.041 fibre/cm3 to 0.173 fibre/cm3. In Poland, the MAC for mineral fibres for total dust amounts to 4 mg/m3 and for respirable mineral fibres to 2 fibres/cm3. PMID- 1435252 TI - [Reference values of selected parameters of lung functions in the population of Bogdanka coal miners]. AB - The aim of the study was to construct and test new equations for calculating FEV1, ITGV and FVC predictive values. Our examined population consisted of 2058 coal miners working underground in Bogdanka colliery (Lublin Basin). The following persons were excluded from out considerations: 1. smokers, 2. miners with pulmonary or allergic diseases history, 3. patients with chronic cough, sputum production or symptoms of chronic rhinitis, 4. persons with bronchial hyperreactivity. Finally, our standard group consisted of 353 coal miners. On the basis of our standard group data, new equations for calculating predictive values were formulated using the multiple regression model. According to these new equations and to equations elaborated by other authors, we calculated predictive values for FEV1, FVC and ITGV in our standard population and expressed results of measurements in percentages of different predictive values. Our predictive values in the standard population were significantly higher than the other authors' values. Percentages of predicted values were lower in the same comparison. We believe that observed differences are linked to a possible self-selection phenomenon in occupationally exposed population, relatively small maximum age of our standard group, possible differences in anthropometric features among examined populations and excluding hyperreactives. Our results seem to emphasize the need of greater attention to the paid on more restrictive use of the specially formulated equations in separate age compartments. PMID- 1435253 TI - The molecular basis for positive regulation of cys promoters in Salmonella typhimurium and Escherichia coli. AB - Most genes required for cysteine biosynthesis in Salmonella typhimurium and Escherichia coli are positively regulated by cysB, which encodes a transcriptional activator belonging to the LysR family of regulatory proteins. CysB protein binds just upstream of the -35 region of positively regulated promoters, where in the presence of inducer it facilitates formation of a transcription initiation complex. CysB protein also autoregulates its own synthesis by binding to the cysB promoter as a repressor. Cysteine down-regulates the pathway by inhibiting synthesis of O-acetylserine, a direct cysteine precursor and possibly an inducer of gene expression. O-Acetylserine spontaneously isomerizes to N-acetylserine, which is clearly an inducer. Sulphide and thiosulphate provide additional regulation by acting as anti-inducers. Inducer stimulates CysB protein binding to sites involved in positive regulation, and inhibits binding to the negatively autoregulated cysB promoter. For three sites with unknown function, binding is stimulated at one and inhibited at the other two. PMID- 1435254 TI - Biological roles of the Escherichia coli RuvA, RuvB and RuvC proteins revealed. AB - In Escherichia coli, the ruvA, ruvB and ruvC gene products are required for genetic recombination and the recombinational repair of DNA damage. New studies suggest that these three proteins function late in recombination and process Holliday junctions made by RecA protein-mediated strand exchange. In vitro, RuvA protein binds a Holliday junction with high affinity and, together with RuvB (an ATPase), promotes ATP-dependent branch migration of the junction leading to the formation of heteroduplex DNA. The third protein, RuvC, which acts independently of RuvA and RuvB, resolves recombination intermediates by specific endonucleolytic cleavage of the Holliday junction. PMID- 1435255 TI - In vitro phosphorylation of AlgR, a regulator of mucoidy in Pseudomonas aeruginosa, by a histidine protein kinase and effects of small phospho-donor molecules. AB - AlgR is a transcriptional regulator of mucoidy in Pseudomonas aeruginosa, a critical virulence factor expressed in cystic fibrosis. AlgR belongs to the superfamily of bacterial signal transduction systems, and has been shown to bind to the algD promoter, a critical point in the regulation of mucoidy. This protein, like other typical response regulators, contains highly conserved residues known to be critical for the phosphorylation and signal transduction processes. However, a typical second component interacting with AlgR has not been identified. Here we demonstrate that AlgR undergoes phosphorylation in vitro when interacting with the well-characterized histidine protein kinase CheA. These results indicate that AlgR is capable of undergoing phosphorylation typical of other two-component signal transduction systems. Moreover, the phosphotransfer reaction between CheA and AlgR was found to be affected by the presence of carbamoyl phosphate, acetyl phosphate, and salts of phosphoramidic acid, recently shown to act as small-molecular-weight phospho-donors in the process of phosphorylation of several response regulators. These findings suggest that AlgR may react with intermediary metabolites such as carbamoyl phosphate and acetyl phosphate, and that these processes may play a role in the control of mucoidy in P. aeruginosa. PMID- 1435256 TI - Frameshifting in the expression of the Escherichia coli trpR gene. AB - The trpR gene of Escherichia coli carries an open reading frame that encodes the trp repressor, 108 amino acids long. Here we show that translation of an additional (+1) reading frame of trpR occurs both in vivo and in vitro. This results in the synthesis of a stable +1 frame polypeptide. Using site-specific mutagenesis, immunological techniques and amino acid sequencing we have found that the N-terminus of the +1 frame product and that of the known 0 frame product are identical but that their C-termini differ. Our results are discussed in relation to the role of natural frameshifting as a regulatory mechanism of gene expression in general, and with respect to tryptophan biosynthesis in particular. PMID- 1435257 TI - Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis. AB - Whereas capsulate strains of Neisseria meningitidis are dependent on pili for adhesion to human endothelial and epithelial cells, strains which lacked assembled pili and were partially capsule-deficient adhered to and invaded human endothelial and epithelial cells if they expressed the Opc protein. Bacteria expressing low or undetectable levels of Opc protein failed to adhere to or invade eukaryotic cells. In addition, the presence of OpaAC751 protein on the surface of bacteria did not increase bacterial interactions with host cells. Association of Opc-expressing bacteria was inhibited by antibodies against Opc. Invasion was dependent on the host-cell cytoskeletal activity and was inhibited by cytochalasin D. In some cells, infected at the apical surface, bacteria emerging from basal surface were detected by electron microscopy. Opc is found in diverse meningococci and may represent a common virulence factor which facilitates adherence and invasion by these bacteria. PMID- 1435258 TI - Transcriptional regulation of the redD transcriptional activator gene accounts for growth-phase-dependent production of the antibiotic undecylprodigiosin in Streptomyces coelicolor A3(2). AB - Transcription of redD, the activator gene required for production of the red pigmented antibiotic undecylprodigiosin by Streptomyces coelicolor A3(2), showed a dramatic increase during the transition from exponential to stationary phase. The increase in redD expression was followed by transcription of redX, a biosynthetic structural gene, and the appearance of the antibiotic in the mycelium, and coincided with the intracellular appearance of ppGpp. However, ppGpp production elicited either by nutritional shift-down of, or addition of serine hydroxamate to, exponentially growing cultures had no stimulatory effect on redD transcription. The presence of redD on a multicopy plasmid resulted in elevated levels of the redD transcript and production of redX and undecylprodigiosin during exponential growth; the normal growth-phase-dependent production of undecylprodigiosin appeared to be mediated entirely through the redD promoter, which shows limited similarity to the consensus sequence for the major class of eubacterial promoters. PMID- 1435259 TI - Transcriptional control, translation and function of the products of the five open reading frames of the Escherichia coli nir operon. AB - Five open reading frames designated nirB, nirD, nirE, nirC and cysG have been identified from the DNA sequence of the Escherichia coli nir operon. Complementation experiments established that the NirB, NirD and CysG polypeptides are essential and sufficient for NADH-dependent nitrite reductase activity (EC 1.6.6.4). A series of plasmids has been constructed in which each of the open reading frames has been fused in-phase with the beta-galactosidase gene, lacZ. Rates of beta-galactosidase synthesis during growth in different media revealed that nirB, -D, -E and -C are transcribed from the FNR-dependent promoter, p-nirB, located just upstream of the nirB gene: expression is co-ordinately repressed by oxygen and induced during anaerobic growth. Although the nirB, -D and -C open reading frames are translated into protein, no translation of nirE mRNA was detected. The cysG gene product is expressed from both p-nirB and a second, FNR independent promoter, p-cysG, located within the nirC gene. No NADH-dependent nitrite reductase activity was detected in extracts from bacteria lacking either NirB or NirD, but a mixture of the two was as active as an extract from wild-type bacteria. Reconstitution of enzyme activity in vitro required stoichiometric quantities of NirB and NirD and was rapid and independent of the temperature during mixing. NirD remained associated with NirB during the initial stages of purification of the active enzyme, suggesting that NirD is a second structural subunit of the enzyme. PMID- 1435260 TI - The glucose kinase gene of Streptomyces coelicolor A3(2): its nucleotide sequence, transcriptional analysis and role in glucose repression. AB - Mutants (glk) of Streptomyces coelicolor A3(2) that are resistant to the non utilizable glucose analogue 2-deoxyglucose are deficient in glucose kinase activity, defective in glucose repression, and usually unable to utilize glucose. A 2.9 kb BclI fragment, previously shown to restore a wild-type phenotype to a glk deletion mutant that lacks the entire segment, contains two complete open reading frames that would encode proteins of 20.1 kDa (ORF2) and 33.1 kDa (ORF3). ORF3 is transcribed from its own promoter, and also from a promoter that initiates transcription upstream of ORF2. A derivative of the temperate phage phi C31 containing ORF3 alone restored a wild-type phenotype when used to lysogenize the deletion mutant. The product of ORF3 is homologous to members of a family of repressor proteins encoded by xylR in Bacillus subtilis and Lactobacillus pentosus, and by nagC in Escherichia coli. Although this might suggest that ORF3 encodes a positive activator for glucose kinase, rather than the enzyme itself, ORF3 restored the ability to metabolize glucose to an E. coli glk mutant, and activity gels of cell extracts of E. coli containing ORF3 cloned in the pT7-7 expression vector demonstrated that the ORF3 product has glucose kinase activity. PMID- 1435261 TI - Cloning and genetic characterization of a Helicobacter pylori flagellin gene. AB - Helicobacter pylori produces polar sheathed flagella, which are believed to be essential for the bacterial colonization of the human gastric mucosa. Here we report on the cloning and genetic characterization of a H. pylori gene encoding the subunit of the flagellar filament, the flagellin. Screening of a genomic library of H. pylori with an oligonucleotide probe derived from the N-terminal amino acid sequence of purified flagellin resulted in a recombinant plasmid clone carrying the flagellin-encoding gene flaA on a 9.3 kb Bg/II fragment. The nucleotide sequence of flaA revealed an open reading frame of 1530 nucleotides, encoding a protein with a predicted molecular mass of 53.2 kDa, which is similar in size with the purified flagellin protein in SDS-polyacrylamide gel electrophoresis. Sequence alignment of H. pylori flagellin (FlaA) with other bacterial flagellins demonstrates a high degree of similarity in the amino terminal and carboxy-terminal regions, including those of the closely related genus Campylobacter (56% overall identity with Campylobacter coli flaA), but little homology in the central domain. Southern hybridizations of chromosomal DNA with flaA-specific probes did not reveal the presence of additional homologous flagellin genes in H. pylori. Sequence analysis of the flaA flanking regions and mapping of the flaA mRNA start site by a primer extension experiment indicated that transcription of the gene is under the control of a sigma 28-specific promoter sequence in H. pylori. The region upstream of the flaA promoter is subject to local DNA modification, resulting in the masking of two out of three closely linked HindIII restriction sites in the chromosome of strain 898-1. Escherichia coli strains harbouring the recombinant plasmid did not produce full length flagellin and data obtained with FlaA fusion proteins using an E. coli plasmid expression system suggest that a distinct nucleotide sequence in the gene interferes with productive translation of this protein in E. coli. PMID- 1435262 TI - Cloning of mycobacterial histidine synthesis genes by complementation of a Mycobacterium smegmatis auxotroph. AB - Histidine-requiring auxotrophs of Mycobacterium smegmatis were isolated following N-methyl-N'-nitro-N-nitrosoguanidine treatment. One of these mutants, his5, was transformed with an M. smegmatis shuttle cosmid library, and complementing clones were isolated at a frequency of approximately 1%. A 2.3 kb fragment was subcloned and sequenced, and found to contain the start of an operon including the hisD gene and part of the hisC gene. No hisG gene was detected upstream of hisD, suggesting that the regulation of histidine biosynthesis in mycobacteria may differ from that of Escherichia coli. The strategy used here will allow the molecular genetics of complex mycobacterial-specific biosynthetic pathways involved in the virulence of pathogenic species to be studied. PMID- 1435263 TI - A multinomial modeling analysis of the mnemonic benefits of bizarre imagery. AB - A series of experiments was conducted to explore the cognitive processes that mediate the bizarreness effect, that is, the finding that bizarre or unusual imagery is recalled better than common imagery. In all experiments, subjects were presented with noun pairs that were embedded within bizarre or common sentences in a mixed-list design. None of the experiments produced a bizarreness effect for cued recall; however, for two of the experiments, the bizarre noun pairs were remembered significantly better than the common pairs for free recall. To determine if these differences were due to the storage or retrieval of the items, a multinomial model for the analysis of imagery mediation in paired-associate learning was developed and applied to the data from the experiments. The model revealed that bizarre sentences benefited the retrieval of the noun pairs but not their storage within memory. The empirical and modeling results are discussed relative to previous findings and theories on the bizarreness effect. PMID- 1435264 TI - Concreteness effects in free recall: the roles of imaginal and relational processing. AB - Two experiments reevaluated the possible role of mental imagery in free recall of concrete and abstract words. In Experiment 1, the number and rate of list presentations were manipulated. Incidental recall following an imagery rating task yielded reliable concreteness effects after two presentations but not after a single presentation, regardless of presentation rate. In Experiment 2, we examined the effects of relational (categorization) and item-specific (imagery rating) processing tasks on memory for categorically related or unrelated concrete and abstract words. Concreteness effects were obtained when unrelated words were sorted into categories but not when they were rated on imagery. Related words failed to yield concreteness effects under any orienting condition. The results support the view that the presence or absence of concreteness effects in free recall depends on the relative salience of distinctive and relational information. This conclusion constrains theoretical explanations of the role of mental imagery in memory and cognition. PMID- 1435265 TI - Degree of learning, interpolated tests, and rate of forgetting. AB - The purpose of the two experiments reported here was to observe the effects of degree of learning, interpolated tests, and retention interval, primarily on the rate of forgetting of a list of words, and secondarily on hypermnesia for those words. In the first experiment, all the subjects had one study trial on a list of 20 common words, followed by two tests of recall. Half of the subjects had further study and test trials until they had learned the words to a criterion of three correct consecutive recalls. Two days later, half of the subjects under each learning condition returned for four retention tests, and 16 days later, all the subjects returned for four tests. Experiment 2 was similar, except that all the subjects had at least three study trials followed by four recall tests on Day 1, intermediate tests were given 2 or 7 days later, and they all had final tests 14 days later. The results showed that rate of forgetting was attenuated by an additional intermediate set of tests but not by criterion learning. Hypermnesia was generally found over the tests that were given after a retention interval of 2 or more days. The best predictor of the amount of hypermnesia over a set of tests was the difference between overall cumulative recall and net recall on the first test of the set. PMID- 1435266 TI - The influence of retrieval on retention. AB - Four experiments tested the hypothesis that successful retrieval of an item from memory affects retention only because the retrieval provides an additional presentation of the target item. Two methods of learning paired associates were compared. In the pure study trial (pure ST condition) method, both items of a pair were presented simultaneously for study. In the test trial/study trial (TTST condition) method, subjects attempted to retrieve the response term during a period in which only the stimulus term was present (and the response term of the pair was presented after a 5-sec delay). Final retention of target items was tested with cued-recall tests. In Experiment 1, there was a reliable advantage in final testing for nonsense-syllable/number pairs in the TTST condition over pairs in the pure ST condition. In Experiment 2, the same result was obtained with Eskimo/English word pairs. This benefit of the TTST condition was not apparently different for final retrieval after 5 min or after 24 h. Experiments 3 and 4 ruled out two artifactual explanations of the TTST advantage observed in the first two experiments. Because performing a memory retrieval (TTST condition) led to better performance than pure study (pure ST condition), the results reject the hypothesis that a successful retrieval is beneficial only to the extent that it provides another study experience. PMID- 1435267 TI - Sentence encoding and implicitly activated memories. AB - Some words have fewer direct associates than others, and, when words varying in set size are studied in a list-learning task, those with smaller sets are more likely to be recalled. This set-size effect is found in cued recall when the words are studied in the absence of related words, but not when studied in the presence of related words. Related words provide context and theoretically inhibit irrelevant associates. The present research determined that set-size effects are found when words are encoded in sentence contexts. In contrast to list-learning experiments, the results of three experiments found such effects even when lexically related words were present in the sentences. Other findings indicated that target-set-size effects were determined by the proximity of related words in the sentence and the nature of the test cue. The results are discussed in relation to a model for explaining set-size effects and to selective findings from the sentence-comprehension literature. PMID- 1435268 TI - Supernatural beliefs, natural kinds, and conceptual structure. AB - This article presents cross-cultural evidence in support of the notion that adults' natural kind concepts are theory based but may be informed by knowledge/belief systems other than the biological. Three groups of subjects from western Nigeria--rural, urban, and elite--participated in the study. Subjects heard stories describing alterations of appearance; that is, one natural kind was made to resemble another in both ritual and nonritual contexts. Subjects then were required to judge the identity of the altered item and to give an explanation for the category judgment. It was predicted that subjects would make more nonpreservation-of-identity category judgments supported by supernatural explanations in the ritual contexts and that subjects' use of supernatural explanations would reflect the extent of their engagement with the supernatural. The first prediction was borne out; the second prediction was only partially supported. Discussion of the results emphasizes the importance of exploring the role of sociocultural factors in conceptual structure. PMID- 1435269 TI - The effects of syntactic structure on letter detection in adjacent function words. AB - In the present study, we examined letter detection in very frequent function-word sequences. It has been claimed that such sequences are processed in a unitized manner, thus preempting access to their constituent letters. In contrast, we showed that letter detection in the words for and the (1) was no more difficult when the words appeared in adjacent locations in a sentence (familiar) than when they appeared apart (less familiar sequence) and (2) was contingent upon the words' syntactic roles within the phrase. Thus, letter detection in for was easier when the sequence was separated by a clause boundary than when the words were part of the same clause. The advantage derived from clause separation was strongest when a comma divided clauses. These results challenge the unitization account of the "missing-letter" effect in common phrases and support a position where this phenomenon is seen to reflect the extraction of phrase structure during reading. PMID- 1435270 TI - The retrieval of controlled and automatic aspects of meaning on direct and indirect tests. AB - The literature concerning implicit memory presents conflicting evidence on the importance of meaning in recovering recently studied words. When the same cues are used during testing, indirect instructions reduce levels of processing effects relative to those obtained with direct instructions, suggesting that meaning is not as likely to be retrieved on indirect tests. However, with certain cues, meaning set size of the studied words affects performance even under indirect instructions, suggesting that meaning is retrieved on such tests. The purpose of the present experiments was to resolve this apparent inconsistency. In Experiment 1, the effects of levels of processing and meaning set size were evaluated under direct and indirect test instructions, with the use of stem and word-fragment cues. In other experiments, beginning and ending stem cues were compared, and levels, set size, and instructional effects were evaluated using meaning cues. The findings indicated that levels effects were determined more by test instructions than by test cues, and that set size effects were determined more by test cues than by test instructions. Implications are discussed for transfer-appropriate processing viewpoints and for a model in which it is assumed that performance is determined by searching either explicit or implicit memories. PMID- 1435271 TI - The word-superiority effect and phonological recoding. AB - Previous work indicates that the locus of the word-superiority effect in letter detection is nonvisual and that letter names, but not letter shapes, are more accessible in words than in nonwords, that is, scrambled collections of letters (e.g., Krueger & Shapiro, 1979; Krueger & Stadtlander, 1991; Massaro, 1979). The nonvisual (verbal or lexical) coding may be phonological, or it may be more abstract. In the present study, a word advantage in the speed of letter detection was found even when the target letter was silent in the six-letter test word (e.g., s in island). Other test words varied in their frequency of occurrence in English and number of syllables (1, 2, or 3). The word advantage was larger for higher frequency words but was not affected by syllable length. The presence of unpronounceable nonwords and silent letters in the words discouraged reliance upon the phonological code but did not thereby eliminate the word advantage. Thus, the word-superiority effect with free viewing is not based entirely upon phonological recoding. PMID- 1435272 TI - Process generalization and the prediction of performance on mental imagery tasks. AB - Kosslyn (1980, 1983) theorized that performance measures on imagery tasks may vary as a function of the existence of independent processes in imaging ability. The present study determined whether improvement can be made in performance on such tasks with practice. It also considered whether performance on such tasks improves with practice and whether this improvement generalizes. Experiment 1 determined whether improvement in a mental rotation task generalizes to improvement in a geometric analogies task, with both tasks weighted in Kosslyn's find process, but not in a line drawing memory task weighted in Kosslyn's regenerate process. In Experiment 2, we examined generalization in improvement from a geometric analogies task to a mental rotation task. In Experiment 3, we tested whether improvement in an animal imagery task (Kosslyn, 1975) generalizes to improvement in a line drawing memory task, with both tasks weighted in Kosslyn's regenerate process, but not to improvement in a mental rotation task. Performance improved with practice on all tasks. Furthermore, performance improved from one task to another only if both tasks loaded on the same process. PMID- 1435273 TI - Age of acquisition, not word frequency, affects object naming, not object recognition. AB - Word frequency is widely believed to affect object naming speed, despite several studies in which it has been reported that frequency effects may be redundant upon age of acquisition. We report, first, a reanalysis of data from the study by Oldfield and Wingfield (1965), which is standardly cited as evidence for a word frequency effect in object naming; then we report two new experiments. The reanalysis of Oldfield and Wingfield shows that age of acquisition is the major determinant of naming speed, and that frequency plays no independent role when its correlation with other variables is taken into account. In Experiment 1, age of acquisition and phoneme length proved to be the primary determinants of object naming speed. Frequency, prototypicality, and imageability had no independent effect. In Experiment 2, subjects classified objects into two semantic categories (natural or man-made). Prototypicality and semantic category were the only variables to have a significant effect on reaction time, with no effect of age of acquisition, frequency, imageability, or word length. We conclude that age of acquisition, not word frequency, affects the retrieval and/or execution of object names, not the process of object recognition. The locus of this effect is discussed, along with the possibility that words learned in early childhood may be more resistant to the effects of brain injury in at least some adult aphasics than words learned somewhat later. PMID- 1435274 TI - The tip-of-the-tongue phenomenon: blocking or partial activation? AB - Tip-of-the-tongue states may represent the momentary unavailability of an otherwise accessible word or the weak activation of an otherwise inaccessible word. In three experiments designed to address these alternative views, subjects attempted to retrieve rare target words from their definitions. The definitions were followed by cues that were related to the targets in sound, by cues that were related in meaning, and by cues that were not related to the targets. Experiment 1 found that compared with unrelated cues, related cue words that were presented immediately after target definitions helped rather than hindered lexical retrieval, and that sound cues were more effective retrieval aids than meaning cues. Experiment 2 replicated these results when cues were presented after an initial target-retrieval attempt. These findings reverse a previous one (Jones, 1989) that was reproduced in Experiment 3 and shown to stem from a small group of unusually difficult target definitions. PMID- 1435276 TI - Prospects for health care reform. PMID- 1435275 TI - Controlling Stroop effects by manipulating expectations for color words. AB - An important characteristic of automatic processing is its uncontrollability. The Stroop phenomenon is regarded as a prototypical example of this characteristic of automatic processing, hence, the Stroop effect should not change when the percentages of color words versus neutral stimuli are manipulated to induce controlled processing. We found that Stroop interference decreased as the percentage of color words increased. Furthermore, the magnitude of the inhibitory component of the Stroop effect was negatively correlated with the percentage of color words; the facilitatory component was insensitive to the manipulation. These results suggest that the Stroop effect is controllable (see Logan, 1980) and that the locus of control is postlexical. The results also suggest that facilitation and inhibition are produced by different mechanisms and challenge those models of the Stroop phenomenon (e.g., Cohen, Dunbar, & McClelland, 1990; Phaf, Van der Heijden, & Hudson, 1990) that assume that a single processing mechanism causes facilitation and inhibition and that control affects facilitation and inhibition alike (Logan, 1980). PMID- 1435277 TI - A professional and personal perspective on families. PMID- 1435278 TI - Imaginative play in children with mental retardation. AB - We examined the play behavior of 18 kindergarten children without mental retardation and 55 children with different levels of mental retardation, all with a developmental age of 4 to 5 years, and found few differences between the groups with regard to activity, types and quality of play, and play content. Qualitative differences as described in the literature were not confirmed. This may have been due to (a) the play situation, which was an individual contact with a stimulating adult and/or (b) the fact that MA and not CA was the standard of comparison. Consequently, mild to moderate mental retardation seems in itself insufficient reason to exclude children from play intervention programs. PMID- 1435279 TI - Courtesy stigma revisited. AB - Building upon Goffman's idea of a courtesy stigma (a stigma acquired as a result of being related to a person with a stigma), I examined how family members maintain community ties while coping with a child who clearly disvalues them. In the early 1970s, I reported that parents develop strategies to make an unmanageable problem manageable. In this paper the various responses to the courtesy stigma concept were examined with regard to the field of mental retardation in particular and disability in general. Also examined was how the social attribution of stigma serves to create distinctions, moral and otherwise, in our society. PMID- 1435280 TI - Developmental disabilities related education, technical assistance, and research activities in developing nations. AB - Few resources are available to identify principles, benefits, and pitfalls concerning international exchanges among professionals in the developmental disabilities field. In the present paper different models for international activities in mental retardation and developmental disabilities were described. Several principles were articulated that characterize successful international programs. These principles were illustrated in a descriptive case study of an international exchange and technical assistance project conducted between a University Affiliated Program and a developing nation. PMID- 1435281 TI - Repair behaviors of children with and without mental retardation. AB - Repair behaviors (a speaker's attempts to make a message understood when the listener indicates a breakdown in communication has occurred) of children with and without mental retardation, ages 8 to 13, were compared as they responded to stacked sequences of requests for clarification (the child's response to a request for clarification is followed by a second and then a third request for clarification). A picture description task with a barrier between the child and examiner was the repair-evoking context. Significant differences were observed in the use of repairs by the two groups. Children with mental retardation did not respond as often as did the children without mental retardation, who also more frequently used details to expand their utterances. Differences were also observed as the request sequence progressed. Evaluation of repair behaviors of children with mental retardation may provide direction for the development of conversational skills. PMID- 1435282 TI - Empirical approach to psychopharmacology for institutionalized individuals with severe or profound mental retardation. AB - There is at this time no conceptual model of psychopharmacology for individuals with severe or profound mental retardation who exhibit behavior disorders that unifies this area of psychopharmacology with general psychiatry practice while addressing the unique aspects of this population. The following article presents a 6-step program of diagnostic inquiry and treatment strategy that allows alternate etiological hypotheses to be tested in a clinical practice framework. This format unifies psychopharmacy practice in mental retardation with psychopharmacy practice in general psychiatry. PMID- 1435283 TI - Functional versus standardized assessment procedures: implications for educational programming. AB - Teacher perceptions of the educational value of two distinct assessment procedures for assessing an 8-year-old student with severe to profound multiple disabilities were compared. Direct service providers (N = 38) from a public school system, randomly distributed into three groups, were asked to use an 8 item Likert-type survey to rate one of three assessment packages: standardized, functional-ecological, and a combined package. Results for four of the eight items were statistically significant. The functional-ecological approach was perceived to be most beneficial for educational intervention. Implications for greater emphasis on a functional-ecological assessment procedure versus standardized procedures were discussed. PMID- 1435284 TI - Increased receptor binding of low-density lipoprotein from individuals consuming a high-carbohydrate, low-saturated-fat diet. AB - The substitution of saturated fat by complex carbohydrate, according to current dietary recommendations, results in a decrease of plasma and low-density lipoprotein (LDL) cholesterol levels. To determine whether this decrease might result from structural and thus functional changes in LDL particles, the binding internalization and degradation of 125I-LDL were measured using TR715-19 cells, a mutant CHO line into which has been transfected the human LDL receptor, and in which measurements of binding are highly reproducible. Eleven nondiabetic subjects (35 +/- 4 years, 27% +/- 3% body fat) were studied after they had 15% protein, and 560 mg cholesterol/d and the other containing 21% fat (6% saturated), 65% carbohydrate, 14% protein, and 524 mg cholesterol/d.LDL cholesterol levels decreased form 125 +/- 6 to 108 +/- 5 mg/dl (P < .01) on the high-carbohydrate diet. There was an increase in the binding affinity of LDL (Kd 6.6 +/- 2.6 v 7.3 +/- 2.7 micrograms/mL +/- SD; P < .02), and internalization (P < .10), and degradation (P < .05) were also higher. The data suggest that decreasing dietary saturated fat may cause alterations in LDL composition that result in increased receptor clearance; this may partially explain the LDL decreasing effect of this dietary change. PMID- 1435285 TI - Type I hyperlipoproteinemia caused by lipoprotein lipase defect in lipid interface recognition was relieved by administration of medium-chain triglyceride. AB - We have previously reported lipoprotein lipase with a defect of lipid-interface recognition in a patient with type I hyperlipoproteinemia. In this patient, lipoprotein lipase from post-heparin plasma (PHP) hydrolyzed monomeric substrate tributyrin, but scarcely hydrolyzed triolein emulsified with Triton X-100 and that in very-low-density lipoproteins ([VLDL] d < 1.006 g/mL), and did not bind to VLDL. The triglyceride (TG) level of this patient did not decrease to less than 1,000 mg/dL with a low-fat diet (1,400 kcal containing 10 g fat/d). When the patient took 30 g medium-chain TG (MCT) in addition to the 1,400-kcal diet, her serum TG level decreased to 250 mg/dL and her clinical signs improved. The low clearance rate of serum TG with heparin injection improved after intake of MCT. Caproic acid levels were maintained at 1.4% and 2.6% in chylomicrons and VLDL after MCT intake, respectively. The patient's lipoprotein lipase hydrolyzed triolein emulsified with 2% tricaprin at the same rate as that of control lipoprotein lipase. The patient's lipoprotein lipase-catalyzed hydrolyzing rate of triolein in chylomicrons obtained after MCT administration was also enhanced up to 70% of that of control lipoprotein lipase. These findings suggest that hypertriglyceridemia caused by lipoprotein lipase with a defect in lipid interface recognition could be relieved with the administration of medium-chain TG, and that one of the mechanisms of this effect might be a modification of TG rich lipoproteins by MCT. PMID- 1435286 TI - The influence of indomethacin, theophylline, and propranolol on ethanol augmentation of glucose-induced insulin secretion. AB - The effect of indomethacin, theophylline, and propranolol on ethanol augmentation of insulin secretion after intravenous glucose stimulation was studied. Intravenous glucose tolerance tests were performed with and without pretreatment with oral ethanol. The role of indomethacin was evaluated in six healthy subjects; the effect of theophylline and propranolol on ethanol augmentation in insulin secretion was studied in five and six subjects, respectively. Ethanol pretreatment was followed by increased insulin (P < .01) and C-peptide areas (P < .01) after intravenous glucose (Area, 0 to 20 minutes). Indomethacin suppressed the ability of ethanol to augment insulin (P < .01) and C-peptide (P < .01) responses. Neither theophylline nor propranolol affected ethanol augmentation of insulin secretion. In conclusion, indomethacin probably interferes with the mechanism for ethanol augmentation of glucose-induced insulin secretion. It is suggested that inositol phospholipids take part in the effect of ethanol to augment insulin secretion, and that indomethacin interferes with the metabolism of inositol phospholipids. PMID- 1435287 TI - In vivo assessment of the metabolic alterations in glucagonoma syndrome. AB - Stable-isotope methodology and indirect calorimetry were used to evaluate metabolic abnormalities in a patient with glucagonoma syndrome manifested by 17% body weight loss, hypoaminoacidemia, and hyperglycemia. Energy expenditure (26 kcal/kg) was the same as that predicted by the Harris-Benedict equation. The rate of appearance (Ra) of intracellular leucine (2.70 mumol/kg/min), an index of protein breakdown, was normal, although the percentage of leucine flux oxidized (31%), an index of amino acid catabolism, was 50% greater than the normal mean value. Glucose Ra in plasma (12.9 mumol/kg/min), representing hepatic glucose production, and glycerol Ra in plasma (3.04 mumol/kg/min), a measurement of whole body lipolysis, were 15% and 25% greater, respectively, than mean values found in normal volunteers. These results suggest that long-term alterations in energy, leucine, glucose, and lipid metabolism in patients with glucagonoma are minimal. However, small long-term metabolic alterations caused by glucagon excess, in conjunction with chronic negative energy balance, could be responsible for the weight loss, hypoaminoacidemia, and hyperglycemia observed in this patient population. PMID- 1435288 TI - Effects of intralipid-induced hypertriglyceridemia on plasma high-density lipoprotein metabolism in the cynomolgus monkey. AB - Low plasma levels of high-density lipoprotein (HDL) and apolipoprotein (apo) A-I often accompany human hypertriglyceridemia. In an animal model of hypertriglyceridemia, the lipoprotein lipase (LPL)-inhibited cynomolgus monkey, we reported that plasma levels of apo A-I were decreased and the fractional catabolic rate (FCR) of HDL apo was increased. To explore whether hypertriglyceridemia alone would alter plasma apo A-I levels and catabolism, hypertriglyceridemia was produced by intravenous (IV) infusion of 20% Intralipid into female cynomolgus monkeys. Baseline plasma triglyceride (TG) levels averaged 106 mg/dL. With infusion of 200 mg/kg/h Intralipid TG, plasma TG levels peaked at 967 mg/dL (range, 413 to 1,069; n = 6). More prolonged or more severe hypertriglyceridemia caused serious complications in several monkeys. Despite the severe hypertriglyceridemia, HDL TG content, HDL apoproteins, and plasma apo A-I levels did not markedly change, suggesting that very little HDL remodeling had occurred. Kinetic studies of HDL protein and apo A-I were performed in four pairs of monkeys. The two tracers were removed from the plasma at identical rates. In five pairs of animals, apo A-I turnover during control and Intralipid-induced hypertriglyceridemia was not significantly different. We hypothesize that apo A-I FCR is a function of HDL composition. Because Intralipid infusion did not alter HDL composition to the same degree as did LPL inhibition, its effects on HDL apo catabolism were not apparent. PMID- 1435289 TI - Apolipoprotein E and lipoprotein lipase reduce macrophage degradation of oxidized very-low-density lipoprotein (VLDL), but increase cellular degradation of native VLDL. AB - Oxidized low-density lipoprotein (Ox-LDL) has been shown to be taken up by the macrophage-scavenger receptor at an enhanced rate in comparison to native LDL, with consequent cellular cholesterol accumulation. In the present study, we analyzed macrophage interaction with very-low-density lipoprotein (VLDL) from normolipidemic subjects (N-VLDL) that was oxidized in the presence of 10 mumol/L copper ions. Oxidized VLDL (Ox-VLDL) contained increased conjugated dienes and malondialdehyde (MDA) equivalents and showed increased electrophoretic mobility. Gradual fragmentation of VLDL apolipoproteins (apo) was noted, with apo B-100 being the first to be fragmented, followed by apo E and apo C. Degradation of Ox VLDL by mouse peritoneal macrophages (MPM) was increased almost twofold in comparison to N-VLDL. Upon incubation of VLDL with lipoprotein lipase (LPL), the LPL-treated lipoprotein demonstrated up to 50% increased degradation by macrophages in comparison to control N-VLDL. However, the degradation of LPL treated Ox-VLDL was decreased by up to 20% in comparison to control Ox-VLDL. Similarly, the addition of apo E to VLDL enhanced its cellular degradation by 56%, whereas a 20% reduction in the degradation of apo E-treated Ox-VLDL was demonstrated in comparison to nontreated Ox-VLDL. These results showed that LPL and apo E, two important regulatory substances in cellular metabolism of plasma lipoproteins, increased macrophage degradation of native VLDL, but reduced the degradation of Ox-VLDL. These inhibitory effects on macrophage uptake of Ox-VLDL suggest that apo E and LPL may possess antiatherogenic potential. PMID- 1435290 TI - Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women. AB - The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-I and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol > or = 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol < or = 1.03 mmol/L [40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.58 (24% increase). Mean values for apo A-I were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-I concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins. PMID- 1435291 TI - Placental transfer and uptake of 2-deoxyglucose in control and diabetic rats. AB - Placental glucose transfer and sequestration were investigated in anesthetized control and streptozotocin-diabetic rats by perfusing the fetal side of one placenta in situ while infusing a mixture of [3H]D-glucose (to measure net transfer after metabolism) and [14C]2-deoxyglucose (to estimate tissue sequestration) into the maternal circulation. No difference was found between transfer ratios (perfusate/simultaneous maternal plasma ratio) of [3H]D-glucose (0.35 +/- 0.06, mean +/- SD) and [14C]2-deoxyglucose (0.36 +/- 0.06) in control rats. Ratios were reduced (P < .001) to the same extent in diabetic rats ([3H]D glucose, 0.13 +/- 0.06; [14C]2-deoxyglucose, 0.15 +/- 0.07). Placental glucose utilization, estimated by the quantity of [14C]2-deoxyglucose-6-phosphate present, was increased from 66 nmol.min-1.g-1 in control to 595 nmol.min-1.g-1 (P < .001) in diabetic rats. Transfer to the perfusion fluid of unlabeled D-glucose was increased (P < .001) in diabetic rats (2.32 mumol/mL) compared with control rats (0.77 mumol/mL) due to elevated (P < .001) maternal plasma glucose levels. Upon phosphorylation, 2-deoxyglucose becomes trapped within the placenta, and therefore these results indicate that all the glucose destined for direct transfer to the fetus is protected from phosphorylation while traversing the placenta, and that diabetes appears to increase placental glucose utilization, but does not induce futile cycling of glucose in an attempt to protect the fetus from an excessive influx of glucose from the mother in the rat. PMID- 1435292 TI - Altered tissue polyamine levels due to ornithine-alpha-ketoglutarate in traumatized growing rats. AB - All cells contain significant amounts of polyamines (PA), and their concentrations are highly regulated. Metabolic activity within a tissue may be reflected in the amount of intracellular PA. Since trauma involves accelerated death and regeneration of tissues, the related levels of PA in extracellular and intracellular fluids may reflect altered protein metabolism. Trauma induces an increased excretion of urinary PA, and the tissues responsible for this whole body activity are not known. During posttraumatic nutritional management, supplementation with ornithine-alpha-ketoglutarate (OKG) seems to improve nitrogen economy. The present study evaluates the significance of muscle, liver, and intestine PA responses in traumatized (bilateral femur fractures) rats to the feeding of an isonitrogenous liquid diet supplemented with or without OKG. Uninjured control rats were pair-fed with respective traumatized rats. After 2 days of starvation and 4 days of feeding, the traumatized and control rats were killed and the tissues were excised and analyzed. Starvation decreases and refeeding increases urinary PA excretion. Trauma-induced PA response is predominantly seen in muscle tissues, and this may be responsible for parallel increases in PA excretion. Liver PA responses show a varying tendency confirming the increased protein synthetic activity due to trauma. Intestine has the highest intracellular PA levels, and there is a general smaller (statistically insignificant) increase in all the individual PA contents due to trauma. OKG supplementation augments tissue and urine PA responses in control rats; however, in trauma rats muscle PA levels show very little change, although nitrogen retention is significantly better (88% to 77%). Mechanistic studies are needed to evaluate the significances of the time-dependent, injury-induced, individual intracellular PA levels. PMID- 1435293 TI - An apparently anomalous relationship between insulin and C-peptide concentrations in their initial response to intravenous glucose. AB - Intravenous glucose tolerance tests (IVGTTs) with determination of plasma glucose, insulin, and C-peptide concentrations were performed in 136 men and 154 women. It was found that in 4% of men and 12% of women the plasma concentration of insulin exceeded that of C-peptide during the initial response to glucose. Subjects exhibiting this phenomenon had lower fasting and post-glucose C-peptide concentrations than those who did not; however, there were no statistically significant differences in glucose or insulin concentrations. The phenomenon was age-related, being absent from individuals aged 35 years and under, while in older age groups it appeared to be more prevalent in women than in men, suggesting an additional effect of menopause. However, in three follow-up IVGTTs performed in a subgroup of postmenopausal women over a period of 18 months, the phenomenon failed to recur in any of the individuals who first exhibited it, although it did occur in others. Our observations suggest the existence of an age related but intermittent decrease in pancreatic insulin secretion, which does not lead to any significant change in plasma insulin concentrations, possibly as a result of reduced hepatic uptake of insulin. One consequence appears to be an excess of insulin over C-peptide during the early part of the IVGTT, which is probably related to the different distributional kinetics of the two peptides. PMID- 1435294 TI - Oxidative modification of lipoprotein(a) and the effect of beta-carotene. AB - Lipoprotein (a) [Lp(a)] particles isolated and purified from human plasma were found to be oxidatively modified when incubated in vitro with human mononuclear cells or Cu2+. This modification, which involved lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS), caused marked changes in the structure and biological properties of Lp(a). Relative to native Lp(a), oxidized particles showed decreases of free amino groups, protein fragmentation, increased negative charge, and high aggregation ability. They were taken up and degraded readily by macrophages in vitro, inducing cholesteryl ester accumulation. When apolipoprotein (a) [apo(a)] was clipped off by exposure to dithiothreitol (DTT), the remaining particle was degraded by macrophages at a significantly lower rate. This observation implies that oxidative modification of apo(a) may have an influence on Lp(a) recognition by scavenger receptors of macrophages. Under the same experimental conditions, low-density lipoprotein (LDL) concentrations equal to those of Lp(a) showed a lower susceptibility to oxidation. This was probably due to higher vitamin E (30% more) and beta-carotene (40% more) content compared with Lp(a), when expressed as a function of cholesterol concentration and measured in the same subject. The addition of beta-carotene to Lp(a) in vitro partially protected Lp(a) against oxidation and aggregation. As a result, uptake of oxidized Lp(a) by macrophages decreased markedly. We conclude that Lp(a) particles are prone to oxidation and that the increased risk of coronary artery disease associated with elevated Lp(a) levels may be related in part to their oxidative modification and uptake by macrophages, resulting in the formation of macrophage-derived foam cells. PMID- 1435295 TI - Probucol protects lipoprotein (a) against oxidative modification. AB - Probucol, which decreases cholesterol levels and has antioxidant properties, was administered orally to patients with familial combined hyperlipidemia and high plasma lipoprotein(a) [Lp(a)] levels. The drug had no effect on Lp(a) concentrations after 4 weeks, but was found to be distributed in both Lp(a) and low-density lipoprotein (LDL). Before treatment, in each case LDL and Lp(a) isolated from the same individual were readily oxidized by copper, resulting in increased electrophoretic mobility and enhanced uptake and degradation by macrophages of both lipoproteins. After probucol treatment, both lipoproteins acquired resistance to in vitro oxidation by copper. Furthermore, probucol prevented their enhanced uptake and degradation by the macrophages. It is surmised that oxidized Lp(a) may carry an atherogenic potential that could be opposed by probucol administration. PMID- 1435296 TI - Effect of hemodialysis on lipid peroxidation and antioxidant system in patients with chronic renal failure. AB - Plasma lipid peroxidation, activity of erythrocyte superoxide dismutase (SOD) and catalase, and serum antioxidant activity (AOA) in uremic patients were examined before and after hemodialysis. An increased level of lipid peroxidation, a decreased serum AOA level, and elevated SOD and normal catalase activity before hemodialysis were observed in uremic patients compared with controls. Hemodialysis was found to produce increased lipid peroxidation, a simultaneous decrease of SOD activity, and lack of any changes in serum AOA and erythrocyte catalase. It is suggested that intensification of lipid peroxidation during hemodialysis could account for accelerated progress of atherosclerosis in patients with renal insufficiency. PMID- 1435297 TI - Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition? AB - Current concepts about the mechanisms underlying the therapeutic effects of dietary methylxanthines (caffeine, theophylline, and theobromine) favor their actions as antagonists of adenosine receptors, and attribute their other possible modes of action, namely those associated with translocation of intracellular calcium, inhibition of phosphodiesterase enzyme (PDE) activity, or the release of catecholamines, to high (near-toxic) doses. From studies measuring the respiration rate of brown adipose tissue (BAT), evidence is provided here that at concentrations compatible with therapeutic doses, the ability of methylxanthines (25 to 50 mumol/L) to potentiate the thermogenic effect of the sympathomimetic drug, ephedrine (0.25 mumol/L), particularly under conditions of caloric restriction, involves a minor contribution of adenosine antagonism, but could mainly be explained by the inhibition of PDE activity. In view of current interest in the pharmacological stimulation of metabolic rate to assist the management of obesity with low-calorie regimens, the targeting of PDE activity is therefore a rational approach in the search for drugs that could potentiate sympathomimetic stimulation of metabolic rate. PMID- 1435299 TI - Is body fat loss a determinant factor in the improvement of carbohydrate and lipid metabolism following aerobic exercise training in obese women? AB - Thirty-one obese, premenopausal women aged 35.4 +/- 5.1 (SD) years exercised for 90 minutes at approximately 55% of maximal aerobic power (VO2max) four to five times a week for a period of 6 months. The training program induced a significant increase in VO2max (P < .001) and significant improvements in carbohydrate and lipid metabolism, as reflected by decreased plasma insulin (INS) concentrations measured in the fasting state and after glucose (GLU) ingestion (INS area, P < .001), by reduced plasma cholesterol (C) and low-density lipoprotein cholesterol (LDL-C) levels (P < .001), and by increased ratios of high-density lipoprotein cholesterol (HDL-C)/LDL-C and HDL2-C/HDL3-C (P < .05 and P < .001, respectively). Changes in body fat mass were positively associated with changes in the INS area/GLU area ratio (r = .49, P < .05) and with changes in very-low-density lipoprotein triglycerides ([VLDL-TG] r = .49, P < .05). Furthermore, changes in the INS area were positively associated with changes in VLDL-TG (r = .51, P < .05). Although no significant mean change in body composition was observed, important individual variation was noted. Twenty women showed a reduction in body fat mass (mean reduction, 2.63 +/- 2.2 kg), whereas 11 women showed an increase in adipose mass (mean increase, 2.79 +/- 2.36 kg). Comparable increases in VO2max were observed between the two groups. The group that showed a decrease in body fat mass with exercise also had significant improvements in carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435298 TI - The morphology and metabolism of intraabdominal adipose tissue in men. AB - Mass, morphology, and metabolism of total adipose tissue and its subcutaneous, visceral, and retroperitoneal subcompartments were examined in 16 men with a wide variation of total body fat. Computerized tomography (CT) scans showed that the intraabdominal fat mass comprised approximately 20% of total fat mass. Visceral and retroperitoneal fat masses were approximately 80% and 20% of total intraabdominal fat mass, respectively. Enlargement of intraabdominal fat depots was due to a parallel adipocyte enlargement only. Direct significant correlations were found between these adipose tissue masses and blood glucose and plasma insulin levels, blood pressure, and liver function tests, while glucose disposal rate during euglycemic glucose clamp measurements at submaximal insulin concentrations (GDR), plasma testosterone, and sex hormone-binding globulin concentrations correlated negatively. The correlations for glucose, insulin, and GDR were strongest with visceral fat mass. Adipose tissue lipid uptake, measured after oral administration of labeled oleic acid in triglyceride, was approximately 50% higher in omental than in subcutaneous adipose tissues. Adipocytes from omental fat also showed a higher lipolytic sensitivity and responsiveness to catecholamines. Furthermore, these adipocytes were less sensitive to the antilipolytic effects of insulin. Both lipid uptake and lipolytic sensitivity and responsiveness showed strong correlations (r = 0.8 to 0.9) to blood glucose and plasma insulin concentrations and also to the GDR (negative), while no such correlations were found with lipid uptake in subcutaneous or retroperitoneal abdominal adipose tissues. Taken together, these results suggest a higher turnover of lipids in visceral than in the other fat depots, which is closely correlated to systemic insulin resistance and glucose metabolism in men. PMID- 1435300 TI - Insulin hypersecretion: a distinctive feature between essential and secondary hypertension. AB - Several studies have demonstrated that patients with hypertension have greater plasma insulin levels than normotensive subjects. The aim of the present study was to clarify if hyperinsulinemia in hypertension is a consequence of either increased pancreatic secretion or decreased hepatic clearance, and to determine whether abnormalities of glucose metabolism are equally present in essential and secondary hypertension. In an observational cross-sectional study, fasting blood glucose, plasma insulin, and plasma C-peptide levels were measured in five patient groups: 34 lean normotensive, 19 overweight normotensive, 25 lean essential hypertensive, 27 overweight essential hypertensive, and 20 secondary hypertensive subjects. The blood glucose/plasma insulin and plasma insulin/plasma C-peptide ratios were calculated as indexes of insulin sensitivity and hepatic insulin clearance, respectively. Subjects with essential hypertension and, to a greater extent, those who were overweight, exhibited significantly higher fasting insulin and C-peptide levels and significantly lower glucose/insulin ratios as compared with lean normotensive subjects. In contrast, no differences were observed between secondary hypertensive and control subjects. Mean blood pressure was significantly and independently correlated to body mass index, plasma insulin and plasma C-peptide levels, and the glucose/insulin ratio. In lean essential hypertensive and secondary hypertensive subjects, the insulin/C-peptide ratios were comparable to controls, indicating normal hepatic insulin clearance. In both overweight groups, a trend to increased insulin/C-peptide ratios was observed. This study shows that in essential hypertensive subjects, hyperinsulinemia is caused by insulin hypersecretion, whereas in overweight subjects, both increased insulin secretion and decreased hepatic insulin clearance might be involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435301 TI - Time-dependent regulation of rat adipose tissue glucose transporter (GLUT4) mRNA and protein by insulin in streptozocin-diabetic and normal rats. AB - Streptozocin (STZ) administration (125 mg/kg) to normal rats resulted in a rapid (24-hour) decrease in circulating insulin levels, marked hyperglycemia, and weight loss. Adipose tissue glucose transporter 4 (GLUT4) mRNA levels decreased approximately eightfold, whereas GLUT4 protein levels were unchanged. However, GLUT4 protein levels decreased approximately 30% by 48 hours and fivefold by 72 hours of insulin deficiency. Although GLUT4 mRNA levels were rapidly restored by insulin therapy (twofold above control levels within 12 hours), GLUT4 protein levels increased only gradually, reaching peak values of 1.5-fold control levels following 7 to 10 days of insulin treatment. Insulin treatment in normal rats increased adipose GLUT4 mRNA levels nearly 100% by 24 hours, while GLUT4 protein levels increased in a more gradual fashion. The delay in GLUT4 protein induction relative to its mRNA was shorter in normal rats treated with insulin than in insulin-treated diabetic rats. These data demonstrate that insulin-induced changes in adipose GLUT4 protein are considerably delayed relative to its mRNA, and that the diabetic state enhances this difference. The known in vivo time dependent effects of insulin treatment on adipocyte glucose transport activity can be at least partly explained by altered specific expression of GLUT4 protein. PMID- 1435302 TI - Carotenoid reversed-phase high-performance liquid chromatography methods: reference compendium. PMID- 1435303 TI - Separation and quantification of carotenoids in human plasma. PMID- 1435304 TI - Measurement of carotenoids in human and monkey retinas. PMID- 1435305 TI - Mammalian metabolism of carotenoids other than beta-carotene. PMID- 1435306 TI - Extraction and analysis by high-performance liquid chromatography of carotenoids in human serum. PMID- 1435307 TI - Analysis of apocarotenoids and retinoids by capillary gas chromatography-mass spectrometry. PMID- 1435308 TI - Surface-enhanced Raman scattering spectroscopy of photosynthetic membranes and complexes. PMID- 1435309 TI - High resolution analysis of carotenoids in human plasma by high-performance liquid chromatography. PMID- 1435310 TI - Separation and quantitation of carotenoids in foods. PMID- 1435311 TI - Distribution of macular pigment components, zeaxanthin and lutein, in human retina. PMID- 1435312 TI - Simultaneous quantitation and separation of carotenoids and retinol in human milk by high-performance liquid chromatography. PMID- 1435313 TI - Antioxidant effects of carotenoids in vivo and in vitro: an overview. PMID- 1435314 TI - Antioxidant radical-scavenging activity of carotenoids and retinoids compared to alpha-tocopherol. PMID- 1435315 TI - Epoxide products of beta-carotene antioxidant reactions. PMID- 1435316 TI - Techniques for studying photoprotective function of carotenoid pigments. PMID- 1435317 TI - Ultrastructural analysis of platelet contractile apparatus. AB - Methods for evaluating the organization, subcellular distribution, and rearrangements in specific constituents of the platelet contractile cytoskeleton are rapidly being developed. The procedures presented and discussed here have yielded useful information. However, a great deal more is required before the role of contractile elements of the cytoskeleton in platelet physiology will be fully understood. The new approaches employing better preservation of platelet structure and immunocytochemistry will undoubtedly provide this knowledge in the near future. PMID- 1435318 TI - Repertoire of platelet receptors. PMID- 1435319 TI - 2-Methylthioadenosine [beta-32P]diphosphate: synthesis and use as probe of platelet ADP receptors. PMID- 1435320 TI - Interaction of nucleotide affinity analog 5'-p-fluorosulfonylbenzoyladenosine with platelet ADP receptor: aggregin. PMID- 1435321 TI - 5-[3H]hydroxytryptamine and [3H]lysergic acid diethylamide binding to human platelets. PMID- 1435322 TI - Homogenization by nitrogen cavitation technique applied to platelet subcellular fractionation. PMID- 1435323 TI - Platelet serotonin transporter. PMID- 1435324 TI - Binding of fibrinogen and von Willebrand factor to platelet glycoprotein IIb-IIIa complex. PMID- 1435325 TI - Platelet membrane glycoprotein IIb-IIIa complex: purification, characterization, and reconstitution into phospholipid vesicles. PMID- 1435326 TI - von Willebrand factor binding to platelet glycoprotein Ib complex. PMID- 1435327 TI - Isolation and characterization of glycoprotein Ib. PMID- 1435328 TI - Platelet glycocalicin. PMID- 1435330 TI - Introduction to platelet structural and functional organization. PMID- 1435329 TI - Preparation and functional characterization of monoclonal antibodies against glycoprotein Ib. PMID- 1435332 TI - Mathematical simulation of prothrombinase. PMID- 1435331 TI - Fibronectin binding to platelets. PMID- 1435333 TI - Isolation of human platelet plasma membranes by glycerol lysis. PMID- 1435334 TI - Isolation of dense granules from human platelets. PMID- 1435335 TI - Platelet insulin receptor. PMID- 1435336 TI - Membrane-impermeant cross-linking reagents for structural and functional analyses of platelet membrane glycoproteins. PMID- 1435337 TI - Surface labeling of platelet membrane glycoproteins. PMID- 1435338 TI - Studying the platelet cytoskeleton in Triton X-100 lysates. PMID- 1435339 TI - Evaluation of platelet surface antigens by fluorescence flow cytometry. PMID- 1435340 TI - Identification of platelet membrane target antigens for human antibodies by immunoblotting. PMID- 1435341 TI - Crossed immunoelectrophoresis of human platelet membranes. PMID- 1435342 TI - Use of correlative microscopy with colloidal gold labeling to demonstrate platelet receptor distribution and movement. PMID- 1435343 TI - Isolation and characterization of platelet membranes prepared by free flow electrophoresis. PMID- 1435344 TI - Purification and characterization of platelet actin, actin-binding protein, and alpha-actinin. PMID- 1435345 TI - Purification and characterization of platelet myosin. PMID- 1435346 TI - Purification and properties of human platelet P235: talin. PMID- 1435347 TI - Detection and identification of Mycobacterium tuberculosis, M. bovis/BCG, and M. avium by two-step polymerase chain reaction. Comparison with ELISA using A60 antigen. AB - We propose a rapid two-step PCR to amplify a 767-bp sequence present in the gene coding for the 65-kD antigen of mycobacteria. The high G+C content (80%) permitted annealing to occur at 70 degrees C, enhancing the specificity. The amplified fragment contains a restriction site for differentiation between M. tuberculosis, M. bovis/BCG, and M. avium. Complete diagnosis can be achieved in less than four hours without labelled probe or nucleic acid transfer. PMID- 1435348 TI - Assisted evaluation of antibiotic resistance development in Pseudomonas aeruginosa from intensive care units. AB - 421 strains of Pseudomonas aeruginosa were isolated from patients admitted to intensive care units and tested with automated systems for sensitivity to 21 antimicrobial agents. Data were collected in a database for evaluation and monitoring of resistance development. Results showed that assisted monitoring of antimicrobial resistance gives continuously updated information, with particular attention to the different local therapeutical schedules. It is therefore advisable that clinicians constantly exchange information with the microbiology laboratory through a hospital information system in which data from different laboratories are pooled in real time. PMID- 1435349 TI - Incidence and level of exotoxin A in proteolytic cell-free cultures of clinical isolates of Pseudomonas aeruginosa collected from hospitals in Riyadh, Saudi Arabia. AB - Mice lethality bioassay revealed that out of 102 proteolytic cell-free cultures of Pseudomonas aeruginosa only 17 (15%) were lethal with values of 19-48 LD50/ml. Antitoxin A antiserum neutralized the lethality providing evidence that the main lethal compound in the cell free cultures was exotoxin A. The neutralization also ruled out the lethal contribution of protease, elastase and phospholipase c. The presence of exotoxin A in a proteolytic environment may indicate less efficient proteolytic action at the stage of toxin production. PMID- 1435350 TI - Effect of ethylenediamine di-o-hydroxyphenylacetic acid and transferrin on the growth of some bacterial strains in vitro. AB - The ability of some bacterial strains to obtain iron from ethylenediamine di-o hydroxyphenylacetic acid (EDDA) or iron-free transferrin, and accordingly grow in their presence, was studied. Growth of Staphylococcus aureus and Yersinia pseudotuberculosis was inhibited by EDDA or by iron-free transferrin. Growth of Streptococcus faecalis, however, was inhibited by iron-free transferrin, but not by EDDA. The other bacterial strains, i.e.; Escherichia coli, Salmonella typhimurium and Shigella dysenteriae were able to grow both in the presence of EDDA or iron-free transferrin. All of the above bacterial strains grow in the presence of iron-saturated transferrin which was not able to bind the iron of the medium and accordingly left the iron of the medium available to them. PMID- 1435351 TI - Extracellular phenoloxidase activity of micromycetes from various taxonomic groups. AB - The ability of Micromycetes strains to produce extracellular phenoloxidases was examined on solid malt agar medium using ten different reagents. We established a POx index summarizing the global activity given by the ten reagents used. The results indicated a wide variability depending on the taxonomic groups, the genera and the species. Some groups were relatively homogeneous, either no and low producers of phenoloxidases (Yeasts, Zygomycetes, genera Aspergillus and Penicillium) or medium and high producers of phenoloxidases (Basidiomycetes, Coelomycetes, Tuberculariales and Dematiaceae), while other groups were very heterogeneous (Ascomycetes, Mucedinaceae). The POx index was significantly higher for strains recently isolated than for strains kept in the fungi collection for a long time. PMID- 1435353 TI - Frequency of Mobiluncus spp. in bacterial vaginosis in Italy. AB - Eleven strains of Mobiluncus spp. were isolated from 35 vaginal secretions of patients with bacterial vaginosis (6 Mobiluncus curtisii and 5 Mobiluncus mulieris). PMID- 1435352 TI - Transfection of E. coli with lambda DNA by electroporation. AB - In the ambit of the B. subtilis genoma sequencing and mapping project, we have set up an electroporation method to transfect E. coli cells with lambda DNA. This methodology presents features that make it preferable to traditional in vitro packaging for some purposes. Here we will illustrate the experimental procedure and the possible applications. PMID- 1435354 TI - Serum cholesterol levels in axenic mice colonized with Enterococcus faecium and Lactobacillus acidophilus. AB - Hypocholesterolemic effect was shown in axenic, mono, bicolonized and conventional mice: the effect was different depending on probiotic properties of intestinal microorganisms. Contamination by Enterococcus faecium CX determined the highest effect: haematic cholesterol level decrease was 16.9% in females and 7.8% in males. In mice contaminated by Lactobacillus acidophilus N5 the decrease of haematic cholesterol levels was less and not relevant in mice contaminated by conventional microflora. Enterococcus faecium CX and Lactobacillus acidophilus N5 strains were able to grow in presence of bile salts, to colonize intestinal tract, to survive at gastric conditions and to assimilate cholesterol (E. faecium more than L. acidophilus). The authors consider the possibility to associate probiotic strains with these characteristics for the health of consumers. PMID- 1435355 TI - The epidemiology of Lyme borreliosis in Italy. AB - Erythema migrans was described in Italy only in 1971 although Italian dermatologists were familiar with it a long time before. In 1983, the first case of Lyme borreliosis with multisystem involvement was identified. The endemic areas in Italy are the Ligurian coast, the province of Friuli Venezia Giulia, and the region surrounding the town of Bologna. In Liguria, the incidence of Lyme disease is about 17/100,000 inhabitants per year. Serosurveys of the general population and of sentinel animals were useless in determining the diffusion of Lyme borreliosis whereas evaluation of people at risk of tick bites and patients with suggestive signs or symptoms was more effective. Among the clinical manifestations of Lyme borreliosis, cutaneous involvement is four times more frequent than neuroborreliosis and arthritis is less frequent in Italy than in the USA. PMID- 1435356 TI - [The antibiotic properties of macrocyclic trichothecene mycotoxins]. AB - Some trichotecenic mycotoxins (verrucarine A, roridines A and H, T-2-toxin) have been studied for their antibiotic effect on a wide spectrum of the yeast cultures (761 strains). The studied substances differ both in their activity and the action character. The yeast strains promising for development of microbiological methods of indication and detoxification of mycotoxins have been revealed. PMID- 1435357 TI - [The destruction of cyanides and their metal complexes by natural bacterial trains]. AB - Natural strains of bacteria of Bacillus and Pseudomonas genera able to destroy cyanides are obtained. Natural strain of Pseudomonas fluorescens B-5040 has a property to destroy high concentration of cyanides (100-200 mg/l) and does not lose the destructive activity in the systems with sufficiently high concentration of mercury (Na3ASO4) compounds (500 mg/l). PMID- 1435358 TI - [Factors that affect transduction in microorganisms]. AB - Data from literature concerning general and specialized transduction in microorganisms are given in the paper. The process of exogenic DNA penetration to the cells of bacteria and participation of protein products of separate phage genes in this process are described. The so-called E-proteins in a set with DNA penetrate through a cell membrane. In phage P22 they are protein products of phage genes 7, 16, 20. In P22 mutants with an altered transducing frequencies (HFT and LFT) the due functions are also coded by the phage genes. It is shown that the process of DNA packing in phages P22, phi 80, lambda and others is genetically determined. The gene transfer frequency depends on UV radiation and the very nature of transducing phages itself. In virulent phages the UV radiation up to inactivation level 95-99% evokes a decrease of their "killer" ability, which is accompanied by an increase of survivability of the formed transductants and, as a result, by enhancement of the transduction transfer frequency. An important role of the transduction analysis for fine mapping of a genome of microorganisms and its significance for practice are shown. A mathematical analysis of the data on cotransduction of linkage markers is presented as such that may be used when determining the value of transduced fragment of a chromosome. PMID- 1435359 TI - [The stability of plasmid pSG 1912 inheritance by the cells of Streptomyces globisporus 1912 and of heterologous streptomycete strains]. AB - Streptomyces globisporus 1912 strain contains plasmid pSG1912 (11, 2kb) determining some phenotypic properties. The plasmid is able to exist and to provide for exhibition of these properties both in autonomous and integrated state. It is established that plasmid pSG1912 and constructed derivatives are stably inherited by cells of S. globisporus 1912 and heterologous hosts, and besides, molecular size and determined properties being retained. PMID- 1435360 TI - [Penicillin resistance in Streptococcus pneumoniae strains]. AB - In this study a total of 87 Streptococcus pneumoniae strains were tested for their susceptibility to penicillin with disk diffusion method by using 5 micrograms methicillin disks. In 68 strains susceptibility to penicillin was also determined by using agar dilution method performed in Mueller-Hinton agar supplemented with 5% sheep blood. Of 63 adult isolates tested with disk-diffusion method 35 strains (55.6%) were susceptible to penicillin, 24 strains (38.1%) had low level resistance and 4 strains (6.3%) had high-level resistance to penicillin. Of 24 S. pneumoniae isolates recovered from children 5 (20.8%) were penicillin susceptible, while 11 (45.8%) had low level resistance and 8 (33.4%) had high level resistance to penicillin. These values were 40 (45.9%), 35 (40.3%) and 12 (13.8%) in total isolates respectively. Of 44 isolates in which MIC values of penicillin were determined by agar dilution method, 34 strains (77.3%) were penicillin susceptible and 10 strains (22.7%) had low level resistance while none of these strains had high level resistance to penicillin. Of 24 children isolates tested with agar dilution method 11 strains (45.8%) were susceptible to penicillin, 8 strains (33.4%) showed low level resistance and 5 strains (20.8%) showed high level resistance to penicillin. For total of 68 isolates these values were 45 (66.1%), 18 (26.4%) and 5 (7.3%) respectively. These findings indicate the need to perform antibiotic susceptibility testing of all pneumococcal isolates to avoid therapeutic failure. PMID- 1435361 TI - [Complement C3 and C4 levels in serum from acute viral hepatitis]. AB - Serial measurements of C3 and C4 complement components were performed in 50 patients with acute, uncomplicated viral hepatitis, in the beginning of the symptoms and in the peaks of serum transaminases. There were 17 patients diagnosed as having Hepatitis A virus (HAV) infection and 33 patients diagnosed as having Hepatitis B virus (HBV) infection. There were 4 women and 46 men with a mean age of 22.1 years. In the sera of 50 healthy control subjects serum C3 and C4 complement components measured, this group was composed of 15 women and 35 men with a mean age of 26 years. The complement component levels were observed to be reduced in both viral infections, where the reduction in C3 serum concentration was found to be statistically significant but reduction in C4 serum concentration was not. PMID- 1435362 TI - [Diagnostic value of ELISA for determining the occurrence of antibodies to antigen A60 in active pulmonary tuberculosis]. AB - IgG antibodies against the purified antigen 60 have been detected in the sera of 48 active, 12 inactive pulmonary tuberculosis patients and 46 tuberculosis free controls with ELISA. Diagnostic value of this test has been evaluated in the conditions of our country. The detection of IgG antibodies against antigen 60 has 67% sensitivity, 90% specificity and 81% positive predictive values. It has been decided that these values have no superiority compared to the sputum examination. It was also found out that sensitivity of antigen 60 ELISA IgG test is very low (22%) in the condition of primary pulmonary tuberculosis cases where direct sputum microscopy sensitivity is also very low. PMID- 1435363 TI - [Development of resistance in bacteria interacting with subinhibitory antibiotic concentrations]. AB - In order to determine the role of subinhibitory concentrations of antibiotics in resistance development, we performed an in vitro trial in which E. coli gained resistance after exposure to low concentrations of ampicillin in serial passages, while MIC values for amikacin and gentamicin increased 2 and 4 times, respectively. Pseudomonas also became resistant to ceftazidime whereas the MIC value for ciprofloxacin increased 10 times. There was not any significant change in susceptibility of S. aureus to vancomycin and amoxicillin + clavulanate. PMID- 1435365 TI - [Bacteriological examination of paper money]. AB - Bacteriological survey of one hundred twenty currency notes was done. Aerobic spore-forming bacilli (91%), Staphylococcus epidermidis (63.3%), Staphylococcus aureus (4.2%), Enterococcus (24.1%), alpha-hem. streptococcus (4.1%), Streptococcus pneumoniae (1.7%), Corynebacterium (7.5%), Lactobacilli (10.8%), Klebsiella pneumoniae (31.7%), Enterobacter (19.2%), E. coli (17.5%), Proteus (1.7%), Pseudomonas aeruginosa (0.8%), Shigella flexneri (0.8%) were isolated from paper money samples. Currency notes in general were bacteriologically contaminated especially with enteric pathogens and potentially pathogens, it was thought that some measures have to be taken to reduce these ill effects. PMID- 1435364 TI - [Importance of the enzyme-linked immunosorbent assay (ELISA) for the serologic diagnosis of tuberculosis]. AB - Tuberculosis is still a major granulomatosis disease in developing countries. The diagnosis of tuberculosis infection frequently creates problems which is related to clinical, radiological and bacteriological investigations. Recently, immunoenzymatic assays provide hopeful results for the serodiagnosis of tuberculosis. In this study, ELISA was evaluated as a serodiagnostic test for tuberculosis. Sera were obtained from 40 pulmonary tuberculosis patients and 15 healthy volunteer donors. The results showed that ELISA could be used in the serologic diagnosis of pulmonary tuberculosis. PMID- 1435366 TI - [Appropriate concentrations of antimicrobial agents in used cadaver pools]. AB - Samples for microbiologic culture were taken from 17 cadaver and 4 cadaver pools in the Department of Anatomy of Gulhane Military Medical Academy (GMMA), Military Faculty of Medicine. Samples were inoculated on bacteriologic and mycologic media and were incubated in aerobic and 10% CO2 atmosphere conditions. From 3 of 4 pools containing different concentration of phenol and formalin, pathogenic bacteria that might be present in normal flora and saprophytic fungi were isolated. In the guidance of these results, in order to keep the cadavers for a long time and laboratory safety, use of formalin and phenol not less than 5% and 4% concentrations of the cadavers respectively and the pools should be taken into consideration. PMID- 1435367 TI - [The growth of some Bradyrhizobium strains in uremic conditions in the presence of antimicrobial substances]. AB - The growth rate of Bradyrhizobium japonicum USDA 110 and its STRR and AMPR mutant strains (resistant to streptomycin and ampicillin respectively), as well as TAL 945 and TAL 946, TAL 947 (mutants of USDA 110 and USDa 138 respectively) on yeast extract mannitol agar (YEMA) containing different concentrations of Crystal Violet and Brilliant Green. According to our results only the growth of Bacillus megaterium B17 was effected from Crystal Violet while the others were not effected from both of dyes in any concentration. PMID- 1435368 TI - [Comparative evaluation of the isolation of dermatophytes by direct laboratory evidence and MSDA with MDTM culture media]. AB - In this study, the hair, skin and nail examples taken from 225 patients suspected dermatophytoses clinically were investigated with direct microscopic examination and cultivated methods. Direct microscopic examination were positive in 135 examples (60%) and dermatophytes were isolated from 109 samples (48.4%). In the isolation of dermatophytes, the effectiveness of modified Sabouraud Dextrose Agar (mSDA) was 93.5% (102/109) and the effectiveness of modified Dermatophyte Test Medium (mDTM) was 95.4% (104/109). It was detected that there were no significant difference between these media for the isolation rate. PMID- 1435369 TI - [Polymerase chain reaction]. AB - The PCR is a method for obtaining millions of copies of a specific DNA sequence in vitro. It appears that this method will lead to several developments in the diagnosis and treatment of many disorders. Especially in genetics and infectious diseases successful results have been achieved. Abnormal gene or infectious agents' genes which may be in less amount in clinical specimens can be amplified with this method. In this way PCR can provide enough genetic material for further diagnostic analysis. PMID- 1435370 TI - [Antinuclear antibodies and disease specificity]. AB - In this review article, the serum antinuclear autoantibody types which are characteristic especially for rheumatic diseases (ANAs, Anti-ss/ds DNA, Anti-sm, Anti-histone, Anti-RNP, Anti-Ro, Anti-La etc.) were discussed on the basis of their biologic properties, their major role in the diagnosis and monitoring disease activity and response to therapy as well as disease specificity. PMID- 1435371 TI - Selection interviewing for medical school admission. PMID- 1435372 TI - Reflections on possible virtues of European medical education. AB - Political and social development in Europe will lead to increased mobility of doctors between countries as well as opening up new possibilities and horizons for educational institutions. In this emerging process the charge that universities are too traditional to change may not be valid when the virtues of academic traditions in Europe are considered. When those virtues are taken into account, they are seen to facilitate the integration of more current goals for future development into undergraduate medical curricula. The use of external examiners between different countries in Europe will promote greater quality in European medical education. PMID- 1435373 TI - A conference on ethics for obstetric and gynaecological clerkship students. AB - Integrating the teaching of medical ethics into medical students' clinical education is challenging, given the competing demands on students' time and the need for teaching to be clinically relevant. This paper describes a model programme for incorporating ethics teaching into the obstetrics and gynaecology clerkship for third-year medical students. The programme is taught by two attending teachers and a medical ethicist with experience teaching in the clinical setting of obstetrics and gynaecology. Objective pretests and posttests showed substantial improvement in students' knowledge, and student feedback has been very positive. PMID- 1435374 TI - Attitudes of elderly patients to medical students. AB - The attitudes of elderly patients towards clinical teaching of medical students was assessed by a structured interview carried out by a doctor unknown to the patient immediately prior to discharge. One hundred and thirty alert patients were approached on three acute geriatric medicine wards in the Royal Liverpool (Teaching) Hospital. A total of 106 (81.5%) patients were suitable for inclusion in the study (mean age, 80.2 years). Twenty-nine per cent did not know what a medical student was despite having been interviewed and examined by one. Fifty nine per cent of patients had no prior knowledge that clinical teaching occurred. Fourteen patients (13 women, 1 man, P < 0.05) objected to being examined. Nineteen women patients were examined by a man student without a chaperone. Students usually (95%) asked permission to interview and examine the patients whereas doctors only asked patients in the context of bedside teaching (33%). Elderly patients were sympathetic towards ('They have to learn') and positive about ('It's good to have them') medical students. However, 29% of patients were not aware that a medical student was going to be a doctor despite being interviewed and examined. We suggest that the term should be used either with explanation or abandoned in favour of 'student doctor'. The level of awareness of clinical teaching was poor and examination of women patients without a chaperone caused distress and should be rectified. PMID- 1435375 TI - Can communication skills be assessed independently of their context? AB - In many examinations, communication skills tend to be treated as if they are a single attribute independent of the context of the communication. However, it is clear that such assessments are confounded by candidates' knowledge or lack of knowledge of the medical issues about which they are communicating. In the 1990 Part One examination for Membership of the Royal New Zealand College of General Practitioners candidates were provided with all the essential knowledge relevant to the problem they were to communicate about. Despite this, performance was still seen to be context specific, demonstrating that such specificity is not purely knowledge related. Candidates completing the examination were observed to share information about the cases with candidates about to commerce. There was no evidence that performance was enhanced by such breaches in examination security. PMID- 1435376 TI - Community-based projects in rural internships: an alternative approach. AB - Supervision of medical interns posted to various primary health centres and rural health training centres by specialists in preventive and social medicine and other clinical disciplines is becoming less and less effective for a number of unavoidable reasons. Because of lack of proper and timely guidance, interns feel that during the 6-month rural internship they do not get enough experience of rural life. In order to provide them with learning experiences in community medicine and orient them in the social dynamics of the community, a new approach involving interns in small community-based projects, probably for the first time, was tried on a pilot basis at the Rural Health Training Centre (RHTC), Sirur, a field practice area of B.J. Medical College, Pune, Maharashtra, India. Interns working at RHTC Sirur completed these community-based projects successfully. Identification of problems, study design analysis and drawing conclusions, based on observation, were all undertaken by the interns under the guidance of the staff of the Department of Preventive and Social Medicine, B.J. Medical College. The opinion poll at the end of the rural internship revealed that 76% of interns considered this experience valuable for improving their knowledge and skills, and 56% though that interaction during these projects was beneficial to the community as well. This experience with community-based projects for interns during their rural posting provides them with an opportunity for interaction with the community. PMID- 1435377 TI - Priorities of undergraduate dental education: what do students think? AB - In recent years there has been an increasing interest in the teaching of behavioural sciences to dental undergraduates, but psychologists and sociologists can meet with resistance to their teaching from both staff and students. In an attempt to understand this resistance further, this paper provides the results of a cross-sectional survey conducted with undergraduate students at two UK dental schools. The results indicate that students believe that training in technical aspects of care (e.g. practice in manual skills, knowledge about anatomy) should assume a substantially higher priority than training in social aspects (e.g. practice in communication skills, knowledge about psychology). The students felt that they were increasingly prepared for both aspects of practice as they progressed through the course, and senior students were more likely to believe that their dental schools should give a higher priority to history-taking and psychological methods to control pain and anxiety than junior students. These results present a considerable challenge for psychologists and sociologists teaching at dental schools and suggest that appropriate curriculum design and integrated teaching may be the way forward. PMID- 1435378 TI - Continuing education for general dental practitioners using a printed distance learning programme. AB - This paper describes the development of a printed distance learning programme by a coordinated team approach. The programme has two components, a resource book and three patient management problem leaflets or challenges and is designed to update general dental practitioners on the management of fissure caries. It includes strategies to meet the educational needs of three groups of general dental practitioners with different educational requirements. It is concluded that the approach described meets the CRISIS criteria for effective continuing education and offers a useful approach to distance learning in dentistry. PMID- 1435379 TI - The market and educational principles in continuing medical education for general practice. AB - In an attempt to increase participation by established general practitioners (GPs) in continuing medical education (CME) the Department of Health in 1990 created an allowance (the Postgraduate Education Allowance, PGEA) to be spent by GPs on the educational provision of their choice. Although the PGEA has increased attendance by established GPs at educational activities, the market created in CME provision has favoured low cost activity of questionable value. This paper examines criteria for the validation of general practice CME, based on the principles of adult learning, which could be used to manage this market. Failure to adopt an appropriate validating process could lead to the PGEA becoming discredited and the imposition of periodic reaccreditation as a means of enforcing participation by GPs in CME. PMID- 1435380 TI - Problem-based learning in distance education: a first exploration in continuing medical education. AB - The Wellcome Tropical Institute has assisted countries in the tropics to establish viable systems of continuing medical education, particularly for young doctors practising in rural areas. As part of this strategy the Institute has developed material for use in distance learning. The first attempt to apply the problem-based learning approach to written material for use by an individual learner in the absence of a tutor led to a trial in Ghana, Kenya and Pakistan to compare a conventionally designed module with a problem-based learning module on the same topic for their respective acceptability, effectiveness and efficiency. The design, implementation and results of these three comparative trials are presented. PMID- 1435381 TI - An assessment of vocational training. AB - A retrospective analysis of the opinions of vocationally trained doctors was obtained from a postal questionnaire. Ninety-eight doctors who had trained in the West of Scotland before the introduction of new criteria in 1985 for the appointment and reappointment of training practices were compared with 107 doctors who had trained following the introduction of the criteria, looking at their rating of training, the frequency of tutorials, value of teaching and research encouragement. There was a significant improvement in the rating of training, frequency of tutorials, research encouragement and enjoyment of training in the group who trained after the new criteria were adopted. The study demonstrates the benefits of vocational training for general practice when criteria are set and followed. This training model may be applicable in other branches of medicine. PMID- 1435382 TI - Effective continuing education: the CRISIS criteria. AB - The need for continuing medical education (CME) is now well recognized. The challenge is to make it effective. CRISIS, an acronymn, stands for the criteria which must be met to produce effective CME programmes: convenience, relevance, individualization, self-assessment, interest, speculation and systematic. CRISIS is a practical tool, based on 15 years of experience in the production and evaluation of CME programmes at the Centre for Medical Education, University of Dundee. The application of the CRISIS criteria to a CME programme will highlight any areas needing improvement and will guide programme producers in the creation of new CME materials. It will also help those responsible for planning CME activities to choose from a range of existing programmes. PMID- 1435384 TI - Continuing education and medical schools. PMID- 1435383 TI - Culinary metaphors in Western medicine: a dilemma of medical students in Africa. AB - A study was conducted of African medical students in two schools to determine their level of understanding of some culinary metaphors in medicine, particularly those used in the description of certain paediatric conditions. The results showed that the vast majority of medical students and young resident doctors are not familiar with many of the European foods, fruits and beverages that are commonly used in medical textbooks to describe disease conditions. In describing disease, it is suggested that medical educators and authors in Europe should endeavour to use terms that are simple and universal. They should not assume universal knowledge of fruits and dishes available in their environment. Medical educators in Africa should also simplify the description by using appropriate terms. PMID- 1435385 TI - A model for extraction of both lipid and water soluble toxins using a procedure from Maharishi Ayurveda. AB - Environmental toxicity from xenobiotic compounds is a major health concern today. This paper presents a hypothetical model for the removal of toxins from the physiology employing procedures of Maharishi Ayurveda, a comprehensive system of natural medicine, which is undergoing renewal. This model combines the use of principles similar to those which are found in lipid extraction, dialysis and bulk flow. A means of testing the hypothesis is also presented. PMID- 1435386 TI - The origin and spread of human leukemia. AB - The human leukemias are a group of hematologic neoplasms characterized by uncontrolled proliferation of cells concerned with blood cell production. The cause(s) of human leukemia remains unknown. Bone marrow (BM) is believed to be the site of origin of human leukemias, although the specific locus(i) and/or cell(s) from which it arises have not been definitively identified. Generally, human leukemias and related proliferative diseases are thought to be clonal in nature; affecting a single hematopoietic stem cell, which then proliferates and replaces the marrow of normal hematopoietic stem cell systems. The condition is believed to be malignant in nature. Results of our current morphologic studies on well-fixed, ideally-stained thin sections of plastic-embedded bone marrow biopsies (BMB) from a large number of acute (AML, ALL) and chronic (CGL, CLL) leukemia patients suggest that human leukemias may not be clonal diseases. Instead, a large population of other resident cells--'endosteal cells'--appears to become involved in the process and it is possible that all members of this group enter the activity simultaneously. This change (transformation) in the endosteal cell population might be due to an abnormality (qualitative or quantitative) of diffusable, humoral factors (yet to be identified) that are responsible for the growth and proliferation of these hematopoietic precursor cells. In this context, the human leukemias may be considered not as malignant, but rather the result of an aberration of factor(s) that control hematopoiesis. In this respect, the human leukemias, particularly AML, ALL and CML, might be analogous to pernicious anemia (megaloblastic anemia) as it was understood 40-50 years ago.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435387 TI - Human cancers and viruses: a hypothesis for immune destruction of tumours caused by certain enveloped viruses using modified viral antigens. AB - Certain viruses which have been identified as possible aetiological agents of human malignant tumours have 2 common characteristics: a) they persist in the human body for long periods despite the presence of antibodies to them and b) they all possess viral envelopes. The envelopes, consisting of phospho lipoproteins are derived from host cells viz nuclear envelope in the case of DNA viruses, and the cell membrane in the case of RNA viruses. These host cell elements on the viral envelope modify the antigenicity of the specific surface antigens which are now perceived by the host immune system as partly self. This in turn blackmails the immune system, if it is to avoid serious auto-immune disease, into producing compromise and ineffective antibodies. The hypothesis proposes the dissolution of the viral envelope in vitro and the re-introduction of the viral core into the host. This should provoke a new uncompromised immune response because it will be directed at the viral core only. This response should eliminate the viral core and with it, the whole enveloped virus, as well as the malignant tumour cells which carry the viral genome derived essentially from the viral core. This approach should introduce a new method for treating and preventing tumours caused by enveloped viruses and the chronic diseases caused by such viruses. PMID- 1435388 TI - Kaposi's sarcoma and HIV. AB - Recently published informed debate affords strong indication that in patients with the Acquired Immune Deficiency Syndrome, HIV cannot, directly or indirectly, be the cause of Kaposi's sarcoma. This paper provides reasons for disallowing a current alternative theory that Kaposi's sarcoma is due to an unidentified sexually transmitted infectious agent and proposes instead that Kaposi's sarcoma is the result of prolonged and repeated exposure to nitrites and/or semen. If this alternative hypothesis is strengthened by confirmation of its predictions then the relationship of HIV to Kaposi's sarcoma, one of the principal AIDS associated diseases, becomes somewhat remote. This may facilitate a shift of emphasis and encourage the development of alternative therapies. PMID- 1435389 TI - Ozonization of blood for the therapy of viral diseases and immunodeficiencies. A hypothesis. AB - In the last 3 decades major autohemotherapy after exposure to ozone has been used in Europe in uncontrolled trials carried out in patients with many illnesses, particularly chronic viral diseases and neoplasms. It appears that the treatment may activate the host's immune system by inducing the production of immunoactive cytokines and it may now be possible to rationalize the procedure, improve the regimen and assess the outcome. It is apparent, however, that such a therapeutic approach, in order to be acceptable, requires an investigative effort of biologists and clinicians. Once this is done, owing to the large range of medical applications and the simplicity of the procedure, autohemotherapy could become very valuable particularly in underdeveloped countries. PMID- 1435390 TI - Is syphilis an incurable disease? AB - Structures which morphologically resemble treponemes have been found in material from patients suffering from latent or late latent syphilis, many of whom have received treatment in the past. These structures were also found in the blood or spinal fluid (SF) of asymptomatic patients with both positive and negative serological tests for syphilis. They have been found in the eye in the presence of active disease as well as in cases without inflammation ('quiet eye'). In latent syphilis, the presence of treponemes after penicillin treatment raises the question of whether the patient is completely cured of syphilis after treatment. Experimental evidence indicates that continued specific antibody production following penicillin treatment depends on the persistence of the specific antigen in the body. This raised three questions: a) Are these stimuli living treponemes? b) Are they still virulent? c) Is syphilis completely curable following penicillin treatment? Our hypothesis is that slowly dividing treponemes are not killed by penicillin. The persistence of living treponemes somewhere in the body may be the proof of this hypothesis. Cases of relapsing neurosyphilis after penicillin treatment have recently been described. We return to the old dilemma: is it a scar-tissue injury or a reactivation of the disease? Since neurosyphilis is asymptomatic, the patient is usually examined because of seroconversion. Only repeated serological analyses and clinical observations of treated cases with immediate penicillin administration can prevent relapse and damage to the central nervous system (CNS) or to other parts of the body. PMID- 1435391 TI - Could cancer be a physiological phenomenon rather than a pathological misfortune? AB - The hypothesis presented here is that cancer is not a phenomenon where the normal functions of the human body break down (like diabetes mellitus or renal failure) but rather a well planned and well coordinated physiological response (similar to the inflammatory response). 'Cancer initiating genes' are presumed neoplastic DNA sequences involved in sensing genome deterioration, consequently enhancing preservation. This genetic trait, different from the concept of oncogenes, actively triggers the neoplastic transformation once genome deterioration is sensed. This self destructive, altruistic phenomenon, obviously devastating to the organism, is nevertheless shown to be a possible mechanism of natural selection. The survival advantage of cancer initiation is discussed using both the concepts of group selection and gene selection. Natural selection, the driving force of evolution, is believed to operate solely on the basis of phenotype differences among individuals. In this paper cancer is hypothesized to be a mechanism that directly scrutinizes the gene contents of the individual, therefore representing natural selection based on genotype differences. PMID- 1435392 TI - Hypothyroid induced hypometabolic state as a possible diagnostic and therapeutic maneuver. AB - Diseased cells possibly function autonomously without as much dependence upon metabolic cues such as thyroid hormone by comparison to normal cells. Therefore if reversible hypothyroidism can be induced briefly in euthyroid patients, conceivably normal cells can be induced into a hypometabolic state while the diseased cells continue at their baseline or near baseline metabolic level. This induced difference could be utilized to isolate and target abnormal cells better. PMID- 1435393 TI - Ascorbate status and xerostomia. AB - Xerostomia, the subjective feeling of dry mouth, affects millions of people particularly the elderly. It is invariably associated with hypofunction of the salivary glands. The amount, rate of secretion, and composition of saliva are regulated by both sympathetic and parasympathetic receptor systems whose stimulation transmits signals through intracellular messengers (cations, nucleotides, phospholipid derivatives) to structures and enzymes within the cell. Salivary glands express a variety of cell-surface receptors including adrenergic (alpha and beta), muscarinic-cholinergic, substance P, vasoactive intestinal peptide hormone, and ATP receptors. Ascorbate which is present in salivary acinar cells in relatively high concentrations, is closely involved in many cellular functions including the metabolism of pyrimidines, intracellular calcium, the catecholamines and other neurotransmitters which regulate salivary gland exocytosis. Ascorbate-dependent carboxyl-terminal peptide alpha-amidation enzyme similar to the pituitary peptidyl-glycine alpha-amidating monooxygase, is also present in salivary glands. It is therefore not fortuitous that the seemingly unrelated numerous factors like aging, drug ingestion, pregnancy, smoking, ionizing radiation, stress, and various pathological states such as cancer, autoimmune disorders, diabetes mellitus, and hypertension often implicated in the causation of xerostomia, all promote increased tissue requirement for and/or depletion of ascorbate. PMID- 1435395 TI - The technical feasibility of cryonics. AB - Cryonic suspension is a method of stabilizing the condition of someone who is terminally ill so that they can be transported to the medical care facilities that will be available in the late 21st or 22nd century. There is little dispute that the condition of a person stored at the temperature of liquid nitrogen is stable, but the process of freezing inflicts a level of damage which cannot be reversed by current medical technology. Could this damage be reversed by future technology? We consider the limits of what medical technology should eventually be able to achieve (based on currently understood chemistry and physics) and whether the repair of frozen tissue is within those limits. PMID- 1435394 TI - Relationship between dietary fatty acid, selenium, and degenerative cardiomyopathy. AB - With the finding of an increasing number of cases of degenerative cardiomyopathy (DCM) amongst patients in Chongqing, Sichuan, People's Republic of China, an attempt has been made to delineate possible etiological factors. In this province endemic for Keshan disease and with considerable consumption of oils high in erucic acid, the latter does not appear to be an operative noxious agent in DCM. Additionally, it does not appear to be caused by excessive oxygen radicals, low levels of antioxidants or low selenium levels. However, lower omega-3 fatty acid levels along with higher serum lipids may be the mechanism, via higher thromboxane levels, of the production of the myocardial degeneration seen in DCM. PMID- 1435396 TI - Beyond positivism: a metaphysical basis for clinical practice? AB - Medicine does not have its own unified body of scientific knowledge. Instead, physicians who are oriented to research make sporadic incursions into the basic sciences such as genetics, biochemistry, immunology, epidemiology, physiology, pharmacology and so on. These latter, taken together, comprise biomedicine which is said to have adopted the positivist epistemology or the Cartesian/Newtonian one that regards the scientist as an uninvolved observer of nature. In effect, medical science has come to rest on a theory of knowledge which links meaning to probability and considers prediction as the scientist's chief task. Like its predecessor, the probability theory of meaning rejects metaphysical speculation and remains connected to observations made, directly or indirectly, by means of the five senses. Despite some brilliant successes touching on relatively uncommon disorders, biomedicine cannot explain most day-to-day clinical activity. An understanding of what transpires between patient and doctor, of its diagnostic potential and therapeutic weight requires hermeneutic, or phenomenological, inquiry which brings about changes in both parties to it. Such a science, as ontological speculation has been called, cannot be deciphered by an epistemology couched in the imagery of physics and chemistry. PMID- 1435397 TI - Deterministic nonlinear chaos in brain function and borderline psychopathological phenomena. AB - There exists a fundamental overall property of the brain which monitors, modulates, and ensures a smoothness of function and which further determines elegance and grace in functioning. This property also imparts a quality of, or a sense of proportion among all other faculties of the brain. It is postulated in this paper that such a property/function, up to now almost taken for granted, is maintained/exercised by a nonlinear deterministic chaotic mode of brain function. If this is the case, borderline psychopathological phenomena, when they flare up, can be explained as resulting from sudden reduction of such a deterministic chaotic mode and the emergence of a pathological order, as the system becomes an oscillating one. PMID- 1435398 TI - Discontinuity in the competitive interaction of tumor cells with the tumor bearing host--a hypotheses. AB - The hypothesis put forward here is that during the growth of a primary tumor ending in metastasis formation, phases occur in which 'unfavourable' conditions arise for the tumor cells. It is proposed that, in order to overcome these 'unfavourable' situations, the tumor cells subsequently secrete a substance designed to have a 'dysfunctional' effect on the normal cells. On the assumption of such a discontinuous secretion by the tumor cells, an investigation is made into the behaviour of certain tumors in humans, together with the findings of previously conducted tests. This leads to the formulation of possible concepts for prophylaxis and treatment. In conclusion, an attempt is made to locate what would be the precise target of such a hypothetical substance. PMID- 1435399 TI - An explanation for the rarity of extraaxial metastases in brain tumors. AB - Primary brain tumors invade and metastasize within the central nervous system (CNS), but rarely extraaxially. A model explaining this behavior is presented. In non-CNS tumors metastases occur since subpopulations of cells capable of invasion and metastases are selected by the tissular environment, and in particular by the connective stroma, which opposes invasion. The CNS lacks a connective stroma, therefore a primary tumor can grow easily in it, but subpopulations capable of metastasization are not selected. Implications of the explanation are: 1) metastasization is largely based on the ability to invade the connective stroma, 2) paradoxically, a less favourable host tissue environment can result in a more aggressive tumoral behavior. PMID- 1435400 TI - Can free radicals induce coronary vasospasm and acute myocardial infarction? AB - Spontaneous acute occlusion of the coronary artery produces regional myocardial ischemia and infarction. This coronary occlusion could be due to rapid progression of atherosclerosis or vasospasm. The factors that can precipitate an acute attack of myocardial infarction or coronary spasm are not known. It is proposed that a stress-induced rise of unesterified arachidonic acid could trigger a leukocyte respiratory burst with the release of free radicals such as superoxide anion (O2-), hydrogen peroxide, hydroxyl radical, and singlet oxygen. These free radicals have the ability to inhibit prostacyclin (PGI2) formation and enhance the breakdown of endothelium-derived vascular relaxing factor (EDRF) which are potent vasodilators and platelet anti-aggregators. This may lead to rapid progression of atherosclerosis or coronary vasospasm leading to acute myocardial infarction. If this is true, free radical quenchers and inhibitors of leukocyte oxidative burst may be useful in the prevention of progression of atherosclerosis and coronary vasospasm. PMID- 1435401 TI - Metabolism of the malignant cell, the role of bacterial spores, and a pictorial presentation to substantiate the latter's presence as an etiological factor in carcinogenesis. AB - The respiration and metabolism of the malignant cell, while in vivo, is anaerobic. This is contrary to a normal animal (human) cell, whose respiration and metabolism is aerobic. There is a factor within the malignant cell which produces a reducing or 'deoxygenating' phenomenon, creating the metabolic anaerobiosis. An animal cell cannot survive without the ultimate oxygen molecule. Yet the malignant cell continues to grow and enlarge despite this oxygen absence. Even more surprising is the fact that the malignant cell requires the circulating flow of blood, otherwise that deficient site or area will ulcerate, slough, or necrotize. Investigative studies clearly indicate that there are present 'spores' of a specific group type of plant micro-organism within the malignant cell, and in the immediate and circumferential area to account for this abnormal physiology. In summarizing all the experimentally uncovered facts, it becomes apparent that the malignant cell, while in vivo, is the consequence of 3 factors of productivity. For the first factor there is the requirement of a tissue site whereby there is an accumulate number of the chronic defense cells as the reticuloendothelial group, squamous, and/or epithelial cells. The second factor requires the presence and phagocytosis of these specific plant bacterial spores that can survive genetically within a sac or cell, and third, for the adequate circulating flow of blood by the host. Because of this, 3 factor product activity, Koch's postulate cannot be fulfilled as a criterion for the etiology of the cancer cell. We have, however, a pictorial summary of the pertinent uncovered facts that, when added together, presents a credible, logical, and valid conclusion to support the concept that these specific bacterial spores contribute to the pathway of activity to associate them as the malefactor in carcinogenesis. PMID- 1435402 TI - Hysterectomy: a time of change. PMID- 1435403 TI - MS Contin: a new string to morphine's bow? PMID- 1435404 TI - Penicillin-resistant pneumococci: will the recent Olympics bring back more to Australia than gold? PMID- 1435405 TI - Radiofrequency catheter ablation as a definitive treatment for paroxysmal supraventricular tachycardia. PMID- 1435406 TI - Intrauterine intravascular transfusion for fetal haemolytic anaemia: the Western Australian experience. AB - OBJECTIVE: To report the first four years' clinical experience with fetal intravascular blood transfusion for the treatment of fetal haemolytic anaemia in Western Australia. SETTING: King Edward Memorial Hospital, Perth, which is the sole tertiary level perinatal centre in Western Australia with a referral base of approximately 25,000 pregnancies each year. METHODS: Transfusion was by injection of packed cells from Rh-negative donors into the fetal umbilical vein near the site of insertion into the placenta. Fetal haemoglobin levels were measured before and after each transfusion. In most cases, the fetus was paralysed by intramuscular tubocurarine. RESULTS: Sixty intravenous transfusions were performed in 20 pregnancies. At the time of the initial transfusion, the mean haemoglobin level was 5.8 g/dL (range, 2.5-8.5 g/dL) and six fetuses had signs of hydrops. The case survival rate was 80% and the procedure survival rate was 93%. Three of the deaths occurred in the first five cases. Caesarean section was performed during two of the procedures, one because of bleeding from the cord puncture site and one because of tamponade of the umbilical vessels. CONCLUSION: Fetal intravascular transfusion is a highly effective treatment for fetal alloimmunisation and allows pregnancies to continue to term and to be delivered vaginally. However, the procedure may be difficult and requires a team approach with ready access to fetal monitoring and emergency caesarean section. Our results suggest that increasing experience of the team is a major factor in improved outcome. PMID- 1435407 TI - Systemic absorption of glycine irrigation solution during endometrial ablation by transcervical endometrial resection. AB - OBJECTIVE: To study systemic absorption of glycine irrigation solution and its consequences during transcervical endometrial resection (TCER). DESIGN, SETTING, PATIENTS: A prospective study of 20 consecutive female patients who underwent elective TCER in a teaching hospital. METHOD: During the operation, patients were monitored with electrocardiography, automated oscillotonometry, pulse oximetry, capnography and a central venous pressure recorder. Plasma sodium and potassium levels were measured at 15-minute intervals. Blood haemoglobin concentration, serum osmolality, and plasma sodium, potassium and glycine concentrations were measured before and after surgery. RESULTS: Plasma glycine concentration increased in all patients after TCER. The highest concentration recorded was 5575 mumol/L. The increase correlated only with the maximum intraoperative decrease in plasma sodium, which was 7 mmol/L in two patients whose plasma glycine level increased by 3001 mumol/L and 5335 mumol/L. CONCLUSION: Systemic absorption of glycine irrigation solution occurred in all patients during TCER. Serial measurement of plasma sodium was necessary to detect this complication. A decrease in plasma sodium level by 7 mmol/L or more during surgery would indicate fluid absorption that could cause severe hyperglycinaemia and other potential complications. PMID- 1435409 TI - Patterns of elder abuse. AB - OBJECTIVE: To establish the rate of occurrence and patterns of elder abuse, and outcomes of intervention, in an Australian population. DESIGN: Retrospective review of medical records over a 12-month period from July 1990 to June 1991. SETTING: An area-based geriatric and rehabilitation service attached to a district hospital. PATIENTS: Referred patients over 65 years of age, who lived in private homes and who met a predetermined definition of elder abuse. RESULTS: The rate of occurrence of elder abuse in the study population was 4.6%, with 29 cases of psychological abuse, 25 cases of physical abuse, 16 cases of neglect, and 13 cases of material/financial abuse. Patterns of abuse were identified and related to dependency of the older person (42%), psychopathology of the abuser (37%), family violence (14%), and carer stress (5%). Interventions and outcomes varied according to the pattern of abuse. CONCLUSION: The rate of occurrence and patterns of abuse of the elderly have been established for the first time in an Australian population. Intervention aimed at reducing the impact of elder abuse is effective, and should be tailored to the pattern of abuse that is occurring. PMID- 1435408 TI - A mammographic screening pilot project in Victoria 1988-1990. The Essendon Breast X-ray Program Collaborative Group. AB - OBJECTIVE: To pilot and evaluate the feasibility and acceptability to women of population based mammographic screening in Victoria. DESIGN: Pilot intervention study in a geographically and demographically defined population. SETTING: Area of contiguous postcodes surrounding the Breast X-ray Unit at the Essendon Hospital. TARGET POPULATION: Women aged 50 to 69 years living in the target area. MAIN OUTCOME MEASURES: Attendance rates, satisfaction, screening rates, surgical biopsy rates, breast cancer detection rates, and surgical treatment. RESULTS: Forty-one per cent of eligible women in the denominator population attended the Breast X-ray Unit in the two-year period; 16,424 women were screened, including 141 women with previous breast cancer. Of every 1000 women screened, 74 were recalled because of mammograms that were suggestive of malignancy, 19 because of technically inadequate mammograms and 16 because of symptoms. All mammograms were read by two radiologists and consensus was required for 12% of films. Of every 1000 asymptomatic women screened, 12.7 had biopsies performed and in 7.1 cancers were detected. In asymptomatic women, the positive predictive value of an abnormal mammogram was 9.4%, and the positive predictive value of a recommendation for biopsy was 55.9%. A total of 131 malignancies were detected, of which 24 (18%) were carcinoma-in-situ. The benign to malignant biopsy ratio was 1:1.31. In 82% of women in whom cancer was detected the breast was conserved. CONCLUSIONS: The Program achieved good standards with respect to mammographic detection, clinical assessment and treatment of women with breast cancer. PMID- 1435410 TI - Verbal interactions in general practice. Information, support and doctor satisfaction. AB - OBJECTIVE: The general practice encounter can be seen as an exchange of information aimed at relief of the patient's presenting symptoms, and it is acknowledged that this goal can most effectively be achieved within the context of the professional's emotional support of the patient. We sought to describe the processes of information exchange and emotional support in detail, and to explore any differences in the speech pattern which were related to the doctors' lesser satisfaction with some consultations. DESIGN: Transcripts of general practice consultations (n = 143) from five medical practitioners were coded and analysed. MAIN OUTCOME MEASURES: The verbal interactions of the consultation were described in categories: for doctors, emotional support, informational support, and diagnostic activity; and for patients, relationship oriented and task oriented. Doctors also rated their satisfaction with each consultation. RESULTS: About two thirds of the speech by both parties was found to be devoted to information exchange in the forms of diagnosis and medical advice, and the rest to the relationship between the participants. Doctors' satisfaction ratings (extremely satisfactory or otherwise) could be predicted from speech and activity variables by means of logistic regression. CONCLUSIONS: This study describes the verbal interaction which is the vehicle for medical helping in general practice, and it forms a foundation for needed research on how certain features of the verbal interaction are related to quality of care. PMID- 1435411 TI - My practice in the Nepal Valley. PMID- 1435412 TI - How to help patients stop smoking. PMID- 1435413 TI - Students can learn medicine with computers. Evaluation of an interactive computer learning package in geriatric medicine. AB - OBJECTIVE: To assess the effectiveness of a computer-aided learning program on dementia. DESIGN: Fourth year medical students were arbitrarily assigned to groups that used a computer-aided learning program (65) or had a tutorial covering similar material (73). These sessions were in addition to a base curriculum in a two-week course in geriatric medicine. MAIN OUTCOME MEASURES: The effectiveness of the teaching sessions was judged by the performance on a multiple choice questionnaire about dementia, given to the students on two occasions, one at the beginning and one at the end of the two-week course. RESULTS: Both groups of students scored significantly better on the second test (computer group, 66% [95% confidence interval, 64-69] to 81% [79-83] and tutorial group, 66% [63-67] to 74% [73-77]). The difference between the groups at the start of the course was not significant (F1,136 = 0.61, P = 0.61); however, there was a significant difference between the groups at the end of the course (F1,136 = 21.83, P < 0.001). CONCLUSION: Both groups improved their knowledge of dementia during the two-week course. Students who used the computer-aided learning programs showed a greater improvement in score. Computer learning programs are effective learning tools and are a useful addition to traditional teaching methods. Further study is required to assess the effects of computer-aided learning programs in long-term studies of dementia knowledge. PMID- 1435414 TI - New vistas in the histopathological assessment of cancer. PMID- 1435415 TI - Active management of the dying patient. AB - OBJECTIVE: To document the process of managing the dying patient in the intensive care unit (ICU) and thus to broaden community debate about an issue that is usually only discussed at a theoretical or philosophical level. SETTING: A six bed ICU in Liverpool Hospital, a 419-bed teaching institution in the southwestern area of Sydney. PATIENTS: Twenty-seven patients, seen over a nine-month period, who had curative treatment withdrawn or withheld. The mean age of the patients was 68 years and the severity of illness, by the APACHE II scoring system, ranged from 12 to 45. INTERVENTIONS: Twenty-three of the 27 patients were mechanically ventilated and 11 were receiving inotropic support. Medical staff usually initiated discussions and sought staff consensus that the patient should be allowed to die (on 23 of 27 occasions). Most relatives (25 of 27) accepted this decision. Support therapies and routine care were stopped according to policy guidelines. Sedatives and narcotics were used in some patients (18 of 27). Twenty one patients died in the ICU and six in the general ward areas. CONCLUSION: Introduction of a policy to guide management of dying patients in intensive care has been accepted by staff. Most dying patients are now managed in accordance with these guidelines. Further discussion and debate of this important issue, by health professionals and society as a whole, is required. PMID- 1435416 TI - Medical illustration: from Netter to computers. PMID- 1435417 TI - Hysterectomy. PMID- 1435418 TI - Demand for smoke-free dining. PMID- 1435419 TI - General practice financing: report of a "think tank". PMID- 1435420 TI - Epidural injection of depot corticosteroids. PMID- 1435421 TI - The management of terminally ill patients. PMID- 1435422 TI - The management of terminally ill patients. PMID- 1435423 TI - The management of terminally ill patients. PMID- 1435424 TI - The management of terminally ill patients. PMID- 1435425 TI - Detection of psychiatric illness with PET. PMID- 1435426 TI - Elderly patients in the emergency department. PMID- 1435427 TI - Male homosexuality. PMID- 1435428 TI - Autologous blood transfusion. PMID- 1435429 TI - Cardiovascular drugs in Australian hospitals. PMID- 1435430 TI - Sulphonylurea hypoglycaemic agents. PMID- 1435431 TI - Sudden death while lawnmowing. PMID- 1435432 TI - The perils of fragmented sleep. PMID- 1435433 TI - Total quality management: the challenge for hospitals in the 1990s. PMID- 1435434 TI - Epidural blockade in obstetrics--how safe? PMID- 1435435 TI - A College of Tropical Medicine for Australasia. PMID- 1435436 TI - Privacy and the computerised medical record. PMID- 1435437 TI - Elderly patients in the emergency department: a prospective study of characteristics and outcome. AB - OBJECTIVE: To describe the characteristics of elderly patients presenting to an emergency department and the outcome for these patients at 90 days. DESIGN: Prospective, descriptive study of all patients over 75 years of age presenting in a four week period. Follow-up data were obtained from the case notes, the Registry of Deaths, the Geriatric Assessment Team and, where necessary, contact with the family doctor. SETTING: The Department of Emergency Medicine at the Royal Hobart Hospital, Tasmania, in late 1989. MAIN OUTCOME MEASURES: Death or increased dependence as defined by permanent institutionalisation, moving in with family, or more than 90 days inpatient care. RESULTS: There were 210 presentations by 191 different patients; 116 were admitted to our hospital (55.2%), and three (1.4%) to other hospitals. Follow-up data were obtained for all but five patients. At 90 days from first presentation 23 had died (12.4%) and in a further 19 (10.2%) their dependence had increased. Risk factors for death were fractured neck of femur or cardiac failure. Risk factors for either death or increased dependence were referral by someone outside the immediate family, neurological disease, cardiac failure, an apparent social/placement problem, and being assessed as needing admission. The strongest predictor was a social problem. Age was not a risk factor. CONCLUSIONS: A predictive formula for poor outcome in this group can be derived. However, outcome may not be altered by admission, or intervention. In the elderly, it is quality rather than duration of life which should be paramount in considering the benefits of therapy. PMID- 1435438 TI - Clinical depression is associated with impaired recovery from stroke. AB - OBJECTIVE: To examine the effect of clinical depression on recovery from stroke. METHOD: We examined a cohort of inpatients with stroke initially at two months after their stroke and again 14 months later. Patients were included if they: (i) provided informed consent; (ii) were able to understand the interview questions; and (iii) survived to follow-up without suffering another stroke or major medical illness. Of 61 consecutive patients, 49 met these criteria. Depression was diagnosed using a structured clinical interview. Three aspects of recovery were measured: (i) functional status; (ii) activities of daily living; and (iii) cognitive performance. RESULTS: Twenty (41%) of the 49 patients were depressed at initial assessment. There were no significant differences in demographic, clinical, stroke or lesion characteristics between the depressed and non depressed patients. At follow-up, depressed patients improved less than non depressed patients in functional status (mean change from baseline, 23% versus 48%) (P = 0.001) and cognitive performance (-1% versus 11%) (P = 0.096). Mean recovery in activities of daily living was not different between the two groups (33% versus 32%) but more of the depressed patients deteriorated over time (20% versus 0%) (P = 0.047). CONCLUSION: Clinical depression occurring soon after stroke is associated with impaired recovery when patients are assessed 14 months later. Depression has a negative effect on recovery in functional status and cognitive performance and may produce deterioration in physical capacity in a number of patients. Physicians would be well advised to be alert for depression and intervene early. Effective treatment of depression may enhance stroke rehabilitation. PMID- 1435439 TI - Multiple medication use in the elderly. Use of prescription and non-prescription drugs in an Australian community setting. AB - OBJECTIVE: To document the extent of polypharmacy or multiple medication use in the elderly. DESIGN: Cross-sectional examination of an age cohort of a community. SETTING: Community-based study in Dubbo, NSW, in 1988-1989. SUBJECTS: All non institutionalised residents aged 60 years and over, numbering 1237 men and 1568 women. MAIN OUTCOME MEASURES: Assessment of use of prescription and non prescription drugs, recent hospitalisation, years of education, psychosocial variables. RESULTS: 18% of men and 25% of women were currently using three or more classes of prescription drugs. The corresponding values for two or more classes of non-prescription drugs were 29% and 44%. Of those who were using multiple prescription drugs 56% of men and 76% of women were also using multiple non-prescription drugs. In a multiple logistic model, the following possible predictors of multiple drug use were included: hospitalisation in the last six months, age, sex, depression, life satisfaction and education. Multiple prescription drug use was significantly predicted by recent hospitalisation (odds ratio [OR] = 2.40; 95% confidence interval [CI], 1.63-3.56), increasing age (e.g. 70-79 years versus 60-69 years; OR = 2.54; CI, 1.97-3.25), female sex (OR = 1.59; CI, 1.25-2.01) and increasing depression (e.g. highest tertile of depression scale versus lowest; OR = 2.52; CI, 1.84-3.42). Multiple non-prescription drug use was significantly predicted by female sex (OR = 2.38; CI, 1.95-2.92) and increasing depression (OR = 2.77; CI, 2.16-3.56). For prescription items, non prescription items, and both categories in combination levels of use 20% above the population average have been documented. CONCLUSIONS: Polypharmacy in the elderly population appears to be predicted by recent hospitalisation, increasing age, female sex and increasing depression. There is potential for drug-drug interaction to occur, but the findings suggest target areas for preventive action. PMID- 1435440 TI - Oestrogen and the breast. 2. The management of the menopausal woman with breast cancer. PMID- 1435441 TI - General practice as a scientific discipline. PMID- 1435442 TI - My Antarctic practice. PMID- 1435443 TI - Complications of immunosuppressive therapy in transplantation. 1: Neoplasia and infection. PMID- 1435444 TI - Complications of immunosuppressive therapy in transplantation. 2: Specific immunosuppressive agents. PMID- 1435445 TI - Intractable leg ulceration caused by cutaneous cholesterol embolism. AB - OBJECTIVE: To present a case of chronic intractable leg ulceration caused by cholesterol crystal embolism. CLINICAL FEATURES: A 76-year-old Caucasian male with a history of ischaemic heart disease had repeated hospital admissions for diagnosis and treatment of recurrent leg ulceration of more than three years' duration. INTERVENTION AND OUTCOME: Definitive diagnosis was made after the third biopsy when the specimen obtained included subcutaneous arteries. Complete healing occurred within three weeks of excision and a skin graft, and subsequent treatment which included systemic steroids. CONCLUSION: Cholesterol crystal embolism is probably an underdiagnosed cause of intractable leg ulceration and can be identified by a biopsy specimen which includes vessels in subcutaneous fat. Systemic steroids may be helpful in its treatment. PMID- 1435446 TI - Severe botulism after eating home-preserved asparagus. AB - OBJECTIVE: To present a case of adult botulism acquired in Queensland. CLINICAL FEATURES: After eating home-preserved asparagus, a 33-year-old man presented with internal and external ophthalmoplegia, bilateral facial nerve palsies, and descending muscle weakness culminating in a sudden respiratory arrest. Electrophysiological testing demonstrated normal nerve conduction velocities and an incremental response of evoked motor potentials on repetitive stimulation, confirming the clinical diagnosis of botulism. INTERVENTION AND OUTCOME: Treatment with trivalent antitoxin, oral treatment with vancomycin and supportive mechanical ventilation for four weeks resulted in complete clinical recovery. Plasmapheresis was also used but its contribution to the patient's improvement is dubious. CONCLUSIONS: Although botulism is rare in Australia, clinicians should be aware of the clinical presentation and the rapidity of confirmation of the diagnosis by electrophysiological testing. Patients should be nursed in an intensive care setting. Regular testing of vital capacity should be performed to determine the need for mechanical ventilation. PMID- 1435448 TI - The evolution of computer viruses. Part 2: Codetic diversification. PMID- 1435447 TI - Ellis-van Creveld syndrome in a Western Australian aboriginal community. Postaxial polydactyly as a heterozygous manifestation? AB - OBJECTIVE: To report two children with Ellis-van Creveld syndrome in an extended kindred of Western Australian Aboriginal descent. Furthermore, to document two family members with isolated postaxial polydactyly of the feet as probable heterozygous manifestations of the Ellis-van Creveld gene. CLINICAL FEATURES: Male and female second cousins with short limbs, postaxial polydactyly and cardiac malformations are described. CONCLUSIONS: It is proposed that founder effect and random genetic drift resulted in a relatively high frequency of the Ellis-van Creveld gene in the Aboriginal people of Western Australia. In addition, further evidence is provided for the postulate that isolated postaxial polydactyly is a heterozygous manifestation of the gene. PMID- 1435449 TI - Some refusals of medical treatment which changed the law of Victoria. PMID- 1435450 TI - Gregg's rubella legacy 1941-1991. PMID- 1435452 TI - Effectiveness, efficiency and the use and misuse of radiology. PMID- 1435451 TI - HIV infection, confidentiality and discrimination. PMID- 1435453 TI - Are the PBS guidelines for lipid-lowering treatment appropriate for patients with CHD? PMID- 1435454 TI - Breast milk and cystic fibrosis. PMID- 1435455 TI - "Home bake" heroin use by injecting drug users. PMID- 1435456 TI - The Disability Support Pension and the "new maths". PMID- 1435457 TI - Glue ear and grommets. PMID- 1435458 TI - Glue ear and grommets. PMID- 1435459 TI - Glue ear and grommets. PMID- 1435460 TI - AIDS--beyond education. PMID- 1435461 TI - Very low energy diets and treating severe obesity. PMID- 1435462 TI - HTLV-I infection in selected populations in Australia and the western Pacific region. PMID- 1435463 TI - Atrophic rhinitis--an unusual complication of typhoid fever. PMID- 1435464 TI - Gastric polyposis: onset during long-term therapy with omeprazole. PMID- 1435465 TI - Skin disorders in Indo-Chinese immigrants. PMID- 1435466 TI - Targets matter, but so does the archery. PMID- 1435467 TI - Cardiovascular disease--how big a problem? PMID- 1435468 TI - Cyclosporin and calcium channel blockers: an exploitable drug interaction? PMID- 1435469 TI - Pet ownership and risk factors for cardiovascular disease. AB - OBJECTIVE: To compare risk factors for cardiovascular disease in pet owners and non-owners. DESIGN AND PATIENTS: Accepted risk factors for cardiovascular disease were measured in 5741 participants attending a free, screening clinic at the Baker Medical Research Institute in Melbourne. Blood pressure, plasma cholesterol and triglyceride values were compared in pet owners (n = 784) and non-owners (n = 4957). RESULTS: Pet owners had significantly lower systolic blood pressure and plasma triglycerides than non-owners. In men, pet owners had significantly lower systolic but not diastolic blood pressure than non-owners, and significantly lower plasma triglyceride levels, and plasma cholesterol levels. In women over 40 years old, systolic but not diastolic pressure was significantly lower in pet owners and plasma triglycerides also tended to be lower. There were no differences in body mass index and self-reported smoking habits were similar, but pet owners reported that they took significantly more exercise than non-owners, and ate more meat and "take-away" foods. The socioeconomic profile of the pet owners and non-owners appeared to be comparable. CONCLUSIONS: Pet owners in our clinic population had lower levels of accepted risk factors for cardiovascular disease, and this was not explicable on the basis of cigarette smoking, diet, body mass index or socioeconomic profile. The possibility that pet ownership reduces cardiovascular risk factors should therefore be investigated. PMID- 1435470 TI - Prospective audit of an aminoglycoside consultative service in a general hospital. AB - OBJECTIVE: To investigate the impact of the introduction of a consultative service on the use, efficiency of dosing and clinical toxicology of the aminoglycoside antibiotics, gentamicin and tobramycin, in a general hospital. METHODS: Two audits were conducted six months and 18 months after the introduction of the consultative service. The audits reviewed the use of drug assay services, the adequacy of drug administration (as measured by serum antibiotic concentrations), indications for prescription, adverse outcomes (by noting markers of nephrotoxicity) and the antibiotic sensitivity of Gram-negative pathogens. The results were compared with the results of an audit conducted before the consultative service was instituted. RESULTS: There was a significant (P < 0.001 by chi 2 test) increase in the use of assays, with drug assays performed in 67% (first audit) and 77% (second audit) of aminoglycoside courses compared with 48.2% in the pre-intervention audit. Sample timing was greatly improved, with more than 70% of the samples collected at the appropriate times. Assay wastage in terms of uninterpretable assay results decreased significantly (P < 0.001) from 42.9% of total assays to 6.3% at the first audit and 3.8% at the second audit. The percentage of assay results in the desirable range increased significantly (P < 0.001) from 39.1% to 71.9% (first audit) and 75.4% (second audit). Pharmacokinetic recommendations were made in 39.1% and 64% of all aminoglycoside courses during the first and second audits respectively, with clinician acceptance of dosage recommendations at 83.1% and 82.8% respectively. For aminoglycoside courses prescribed for therapeutic reasons, 97.9% (first audit, n = 325) and 98.6% (second audit, n = 280) of indications for use were judged as clinically appropriate. The incidence of suspected aminoglycoside induced nephrotoxicity was reduced from 8.9% of patients to 1.6% (first audit, P < 0.001) and 2.4% (second audit). Bacterial sensitivity audits showed that the great majority of clinical isolates of target organisms (n = 3523, Year 1 and n = 3385, Year 2) were sensitive to gentamicin (92.2% and 91.5% respectively) and tobramycin (98.1% and 98.8% respectively); these aminoglycosides exceeded all alternative agents in effectiveness, including first and third generation cephalosporins. CONCLUSIONS: The overall results indicate that introduction of the consultative service had a positive impact on the effective use of aminoglycosides, with a marked decrease in clinical toxicity. These influences were shown to persist for at least 18 months. The availability of reliable predictive techniques to reduce toxicity allows active promotion of aminoglycosides as the agents of choice on grounds of efficacy and economy. PMID- 1435471 TI - The use of a videotaped questionnaire for studying asthma prevalence. A pilot study among New Zealand adolescents. AB - OBJECTIVE: To examine the feasibility of measuring asthma prevalence by means of an audio-visual presentation of asthma symptoms and signs (video questionnaire) and to compare this technique with a standard written questionnaire for predicting bronchial hyperresponsiveness. DESIGN: A cross-sectional study comparing the ability of a video questionnaire and a written, interviewer administered questionnaire to predict bronchial hyperresponsiveness. Bronchial responsiveness was measured with hand held nebulisers. SETTING: Community survey of a New Zealand rural secondary school. SUBJECTS: A total of 456 adolescent school children aged 12-19 years (mean 15.5 years). OUTCOME MEASURES: Comparison of the sensitivity and specificity of a standard questionnaire versus a video questionnaire for bronchial hyperresponsiveness. RESULTS: The technique was easy to administer in the community setting. Overall sensitivity and specificity for the prediction of bronchial hyperresponsiveness were similar for the video and interviewer administered questionnaires. CONCLUSIONS: This new technique is easily used in the community setting, and gives predictions of bronchial hyperresponsiveness similar to those of a standard interviewer administered questionnaire. Further examination of the technique in comparisons of asthma prevalence among different populations is planned. PMID- 1435472 TI - Renal transplantation--an effective therapy in the 1990s. PMID- 1435473 TI - Acute gastrocnemius myositis. Another extraintestinal manifestation of Crohn's disease. AB - OBJECTIVE: To present the first case in Australia of skeletal muscle inflammation as a manifestation of Crohn's disease. CLINICAL FEATURES: A 50-year-old man was admitted to hospital with a two-week history of bloody diarrhoea, weight loss of 3 kg, soreness of his calf and thigh muscles, and night sweats. A clinical diagnosis of acute Crohn's gastrocnemius myositis was made. Muscle biopsy was not performed. INTERVENTION AND OUTCOME: He was prescribed hydrocortisone by the intravenous route, which was replaced by prednisone by mouth. The myositis resolved completely within 48 hours. CONCLUSION: Corticosteroids are an effective treatment for this rare extraintestinal manifestation of Crohn's disease. Invasive investigations can be reserved for those who fail to respond. PMID- 1435474 TI - Assessing health status in general practice. PMID- 1435475 TI - General practice as a caring discipline. PMID- 1435476 TI - Pulmonary oedema--prehospital treatment. Caution with morphine dosage. AB - OBJECTIVE: To inform doctors of potential hazards if opioids are administered in excessive doses to patients with acute pulmonary oedema. CLINICAL FEATURES: Three elderly patients were unresponsive and hypotensive on arrival in the emergency department. All had received morphine parenterally as a component of prehospital treatment for acute pulmonary oedema. INTERVENTIONS AND OUTCOME: All were given naloxone intravenously, regained consciousness and had a rise in blood pressure. CONCLUSION: Parenteral administration of opioids should be used with caution in acute pulmonary oedema. The authors present a protocol for prehospital drug therapy. PMID- 1435477 TI - Eosinophilic fasciitis associated with L-tryptophan ingestion. AB - OBJECTIVE: To present the first case of eosinophilic fasciitis associated with L tryptophan ingestion. CLINICAL FEATURES: A 23-year-old Australian man developed myalgia and weakness, and later the clinical features of eosinophilic fasciitis, while taking L-tryptophan. INTERVENTION AND OUTCOME: The amino acid supplementation was discontinued and he was treated with prednisone (30 mg/day) for six weeks with significant improvement. CONCLUSION: In sclerodermatous skin diseases, such as eosinophilic fasciitis, the possibility of ingestion of tryptophan-containing products should be considered. PMID- 1435479 TI - Information about side effects--how much to tell the patient. PMID- 1435478 TI - Successful treatment of disseminated strongyloidiasis. AB - OBJECTIVE: To report the successful treatment of Strongyloides stercoralis hyperinfection, which is usually lethal but in this case was diagnosed in its early stages. CLINICAL FEATURES: A 44-year-old woman, who had spent much of her life in Fiji and India, was treated with a high dose of prednisolone for rheumatoid arthritis complicated by gold lung. The onset of abdominal symptoms, an exacerbation of respiratory symptoms, and a persistent high eosinophil count and serum IgE level, led to the detection of numerous Strongyloides larvae in her faeces and sputum. INTERVENTION AND OUTCOME: She was treated with thiabendazole for five days, then mebendazole for one month, and the dose of prednisolone was reduced. Clinical symptoms and signs improved within days and after one week parasites could not be found in her faeces. After six months, enzyme-linked immunosorbent assay for Strongyloides infection gave a reading which was 40% of the initial level but still in the positive range. CONCLUSION: Steroid therapy in individuals with chronic, subclinical strongyloidiasis predisposes to the insidious development of hyperinfection syndrome, which has a high mortality rate. If detected early, this complication can be treated effectively. It can be prevented by actively seeking Strongyloides infection, by faecal microscopy and culture techniques and by serological tests, in high-risk individuals, such as immigrants from endemic areas. PMID- 1435480 TI - Informed consent in modern medical practice. PMID- 1435482 TI - Royal Australian College of Ophthalmologists policy statement on sunglasses. PMID- 1435481 TI - Human albumin solutions: consensus statements for use in selected clinical situations. Subcommittee of the Victorian Drug Usage Advisory Committee. AB - OBJECTIVE: To establish consensus statements for the use of human albumin solutions in clinical situations identified as responsible for the major use of human albumin products. DESIGN AND SETTING: Working parties comprised of specialists in intensive care, renal medicine, cardiothoracic anaesthesia, gastroenterology, haematology and transfusion medicine, were convened to develop consensus statements for the use of human albumin solutions. RESULTS: Specific statements have been formulated to guide the clinician in the use of human albumin solutions for hypovolaemia or hypoalbuminaemia (particularly in intensive care units), cardiothoracic surgery, therapeutic plasma exchange and patients with ascites or protein-losing states in gastroenterology. CONCLUSIONS: These statements, with wide dissemination, will promote consistency in the use of human albumin products in clinical practice and become a reference for future audits on the use of these products. PMID- 1435483 TI - Subdural haematoma presenting as an isolated speech disorder. PMID- 1435484 TI - Gastrointestinal endoscopy. PMID- 1435485 TI - The Papanicolaou smear histories of 237 patients with cervical cancer. PMID- 1435486 TI - The Papanicolaou smear histories of 237 patients with cervical cancer. PMID- 1435487 TI - Resort scuba diving. PMID- 1435488 TI - Laparoscopic cholecystectomy: a plea to preserve the sphincter of Oddi. PMID- 1435489 TI - Rapid rise in serum theophylline concentration after overdose with sustained release theophylline. PMID- 1435490 TI - Euthanasia in Holland. PMID- 1435491 TI - Glutaraldehyde. PMID- 1435492 TI - Education is not enough to reduce the adverse consequences of pharmaceutical drug use. PMID- 1435493 TI - Rigid bronchoscopy during high-frequency jet ventilation in the emergency department. PMID- 1435494 TI - In search of the pathogenesis of refractory cervicobrachial pain syndrome. PMID- 1435495 TI - Compliance barriers and hidden needs in hypertension. PMID- 1435496 TI - [Tumor development and new therapeutic possibilities]. PMID- 1435497 TI - [Gene probes in the detection of leukemia cells]. PMID- 1435498 TI - [Fungal infections in man. Part 5: Mycoses of various mucous membranes]. PMID- 1435499 TI - The psychology of shoplifting. 1954. PMID- 1435500 TI - Prosecuting serious fraud--the role of the Serious Fraud Office. PMID- 1435501 TI - Ethical dilemmas in fetal medicine. PMID- 1435502 TI - What is the patient's charter? PMID- 1435503 TI - Medical negligence litigation: the need for reform. PMID- 1435504 TI - Enoxacin--a new fluoroquinolone. PMID- 1435505 TI - Teniposide for acute lymphoblastic leukemia. PMID- 1435506 TI - Cefpodoxime proxetil--a new oral cephalosporin. PMID- 1435507 TI - Topical treatment for bacterial vaginosis. PMID- 1435508 TI - Origin of mineral crystal growth in collagen fibrils. AB - Collagen fibrils from young turkey-leg tendons, just beginning to mineralize, were stained with uranyl acetate and examined by electron microscopy. Small needle-like mineral crystals were observed and located, in relation to the collagen banding pattern, as originating at the e band in the gap region and near the surface of the fibrils. These are evidently the sites of crystal nucleation. They lie near binding locations on collagen fibrils of two glycosylated proteins believed to be implicated in the mineralization process, as well as the sites of early crystals in embryonic fowl bones. PMID- 1435509 TI - Self-assembly into fibrils of a homotrimer of type I collagen. AB - Type I collagen, the most abundant structural protein in vertebrates, is comprised of two alpha 1(I) chains and one alpha 2(I) chain. Fibroblasts from a proband with osteogenesis imperfecta, however, were shown to synthesize a type I procollagen that was a homotrimer of pro alpha 1(I) chains. The absence of pro alpha 2(I) chains in the procollagen provided a unique opportunity to assess the role of the alpha 2(I) chain in collagen fibrillogenesis by examining the self assembly de novo of the homotrimeric collagen generated in vitro. The results demonstrated that the fibrils formed by the homotrimeric collagen had an asymmetric banding pattern similar to fibrils of normal heterotrimeric type I collagen. However, the efficiency for self-assembly of the homotrimer into fibrils was markedly reduced in that the critical concentration at 37 degrees C was 40-fold greater than for self-assembly of the heterotrimeric molecule. A van't Hoff-type plot of the data was used to determine values for delta G, delta H and delta S. The values indicated the self-assembly of the homotrimer is similar to self-assembly of the heterotrimer in that the process is entropy driven. The process is, however, less favorable in that the delta G value was 10 kJ/mol less negative. The results suggest that the presence of the alpha 2(I) chain in type I collagen helps drive the self-assembly process, probably because the alpha 2(I) chain is more hydrophobic than the alpha 1(I) chain and, therefore, smaller amounts of structured water may be lost during self-assembly of the homotrimer than during self-assembly of the heterotrimer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435510 TI - Inhibition of calcification in vivo by acyl azide cross-linking of a collagen glycosaminoglycan sponge. AB - A collagen-glycosaminoglycan sponge composed of collagen (80%), chondroitin-4 sulfate (13.3%) and heparan sulfate (6.6%) was cross-linked using the acyl azide method or glutaraldehyde (0.0075%). Under optimal conditions, the denaturation temperature (Td) was raised to 69 degrees C (+23 degrees C) for the sponge treated by the acyl azide method and to 68 degrees C (+22 degrees C) for that treated with glutaraldehyde. The biocompatibility of the treated and control sponges was studied up to 3 months after subcutaneous implantation in rats by analysing cellular responses and calcification by histological and ultrastructural methods. A control collagen-glycosaminoglycan sponge was rapidly invaded by mononuclear cells (8 days), with the formation of granulation tissue. Calcification was observed at the periphery of the implant after 8 days, and the implant was entirely calcified after 15 days; it was degraded progressively after 30 days. Acyl azide treatment increased the persistence of the sponge in vivo up to 90 days and inhibited its calcification. A glutaraldehyde-treated sponge was completely calcified after 15 days, and calcified nodules persisted after 90 days. Thus, acyl azide method efficiently cross-linked a collagen glycosaminoglycan sponge and inhibited calcification after subcutaneous implantation in rats (at least up to 90 days after implantation). PMID- 1435511 TI - Endochondral ossification and de novo collagen synthesis during repair of the rat Achilles tendon. AB - Ectopic endochondral ossification is the inevitable consequence of midpoint tenotomy of the rat Achilles tendon. After tenotomy, the tendon stumps retract and the intervening space fills with granulation tissue. The initiation of chondrogenesis is indicated by pre-chondrocytic cells forming a "whorled" pattern, both at the tendon stumps and within the granulation tissue and later clearly differentiating into cartilage nodules. The chondrocytes rapidly "hypertrophy" exhibiting an orientation similar to that in epiphyseal growth plates. The nodules of cartilage are then replaced, by bone. During this total process, a temporal and spatial pattern of new collagen synthesis can be demonstrated, both biochemically and immunocytochemically. Both the cartilage and the subsequent bone closely resemble the tissue in developing long bones enabling this model to be used to study the initial switching on of normal chondrogenesis and osteogenesis in a system not normally programmed to do so. PMID- 1435512 TI - Production of both 92- and 72-kDa gelatinases by bone cells. AB - We investigated the ability of murine bone organ cultures and osteoblast-like bone cells to produce 72- and 92-kDa gelatinase. 4-6 day newborn mouse calvaria cultures were found to release gelatinase activity into their conditioned medium (CM). This activity was increased by four stimulators of resorption, tumor necrosis factor alpha (TNF), interleukin-1 alpha (IL-1), parathyroid hormone (PTH) and the active phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Both the 72- and 92-kDa forms of gelatinase were produced by murine bone cultures. In unstimulated bones 72-kDa gelatinase activity was approximately equal to that of the 92-kDa enzyme. IL-1, TNF, PTH and TPA all increased 92-kDa gelatinase activity in the CM of the bone cultures by about 2- to 2.5-fold. In addition TPA and IL-1 also increased 72-kDa gelatinase activity. In unstimulated osteoblast-like MC3T3-E1 cell cultures 72-kDa gelatinase enzyme activity was much greater than 92-kDa activity and was not substantially regulated (less than 40% change) by IL-1, TNF or PTH. In contrast, these agents stimulated 92-kDa gelatinase activity by 2- to 5-fold. As with the MC3T3-E1 cells, primary cells constitutively produced both 72-kDa and 92-kDa gelatinase. This was true for cells with both the most differentiated osteoblast-like phenotype (populations 3 and 4) and the least osteoblast-like phenotype (populations 1 and 2). In unstimulated cultures of all 4-primary populations, 92-kDa gelatinase production was less than 72-kDa and IL-1, TNF and PTH had only small effects on 72-kDa production in any of the populations (less than 60% change).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435513 TI - Age-related changes in the concentration of hydroxypyridinium crosslinks in functionally different skeletal muscles. AB - High-performance liquid chromatography methods were developed to measure the concentration of hydroxypyridinium crosslinks in the intramuscular collagen and tendinous parts of functionally different skeletal muscles at different ages. A significant increase in pyridinoline concentration took place during maturation reaching 0.32 +/- 0.07 (mol/mol collagen) in soleus (slow plantar flexor) and 0.28 +/- 0.07 in plantaris (fast "mixed" plantar flexor) at the age of 4 months. In medial and lateral gastrocnemius (fast "mixed" plantar flexors) the pyridinoline concentrations (mol/mol collagen) reached 0.24 +/- 0.06 and 0.19 +/- 0.04, respectively, similar to those in both the extensor digitorum longus (fast "mixed" dorsi flexor) and rectus femoris (fast "mixed" knee extensor) muscles, but higher than in the fast "mixed" dorsi flexor muscle, anterior tibialis (0.11 +/- 0.05 mol/mol). By comparison, pyridinoline concentrations of 0.33 mol/mol collagen (+/- 0.10) was measured from longissimus dorsi, a slow-twitch back posture muscle. After maturation the most significant increase in pyridinoline concentration was measured in soleus and gastrocnemius muscles. No differences in the crosslinking between different parts of muscle belly were noticed at any time point. However, significantly fewer pyridinoline crosslinks were found in tendinous parts of soleus, extensor digitorum longus and anterior tibialis than in intramuscular collagen. The concentration of pyridinoline crosslinks tended to be highest in slow-twitch postural muscles, soleus and longissimus dorsi, and generally higher in plantar flexors which are exposed to higher stretch than dorsal flexors. The reasons for the unexpectedly low concentrations of pyridinoline crosslinks in the tendinous parts of muscles remain to be clarified. PMID- 1435514 TI - Studies of collagen in bone and dentin matrix of a Columbian mammoth (late Pleistocene) of central Utah. AB - A Columbian mammoth, Mammuthus columbi, was excavated at an elevation of 9000 feet in Huntington Canyon, Emery County, Utah. Radiocarbon dates on the skeleton indicated death approximately 11,200 years ago. The skeleton was removed from postglacial, Late Quaternary, lake sediments deposited as glacial runoff approximately 9500 years ago. The bones and teeth were especially well preserved in a saturated lake bed. After excavation the bones and teeth were preserved by controlled desiccation, without hardeners, over a period of 9 months. Microradiography, light and electron microscopy, medium and high angle X-ray diffraction, amino acid analysis and cyanogen bromide peptide mapping were undertaken to evaluate the packing, organization, and preservation of collagen in bone and dentin of this mammoth. Microradiography and light microscopy showed that the bone consisted of especially well preserved compact and trabecular bone, and electron microscopy of demineralized bone and tusk showed that the matrix consisted of lamellae of densely packed cylindrical collagen fibrils. Cell remnants with intact nuclei, with or without a nucleolus, as well as variable lengths of plasma membrane were occasionally present on the surface of bony trabecula. Remnants of odontoblast processes were present in some dentin tubules. High and low angle X-ray diffraction demonstrated that the demineralized matrix contained native collagen molecules and amino acid analysis showed that the composition was comparable to that of type I collagen. Cyanogen bromide peptide mapping indicated that the major peptides of type I collagen were present and had the same electrophoretic mobility as that of type I collagen of demineralized Asian elephant bone and rat tail tendon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435515 TI - Proteoglycan synthesis in normotensive and spontaneously hypertensive rat arteries in vitro. AB - Proteoglycans (PGs) were analyzed and compared in the media of the thoracic aorta, abdominal aorta, left carotid artery and superior mesenteric artery of age matched Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Two ages were examined; 10 week old, during the development of hypertension and 28 week old, when hypertension is well established in the SHR. Large chondroitin sulfate PG, large heparan sulfate PG and biglycan (PGI) and decorin (PGII) small PGs were identified. Biglycan was the predominant small PG found in all arteries. Newly synthesized PGs were labelled in vitro with 35SO4 for quantitation. The synthesis of large and small PGs was similar in the media of the thoracic aorta, abdominal aorta, left carotid artery, and superior mesenteric artery. The large to small ratio value, a measure of the artery PG composition, was also similar among the four arteries but was highest in the mesenteric artery. In both WKY and SHR arteries there was significantly decreased PG synthesis in the 28-week old compared to 10-week old animals. This was especially true for large PG. Hypertensive changes in PG synthesis were seen mainly in the carotid artery. In this artery, synthesis of both large and small PG was increased in the SHR, at both ages. The ratio of large to small PG was not significantly different between SHR and WKY arteries. We conclude that 28-week old WKY and SHR rat arteries synthesize less large and small PG than 10-week old arteries. The most prominent change seen in hypertensive rats is an increase in PG synthesis in the carotid artery. PMID- 1435516 TI - In-situ hybridization of tropoelastin mRNA during the development of the multilayered neonatal rat aortic smooth muscle cell culture. AB - Cultured neonatal rat aortic smooth muscle cells are active in synthesizing and depositing large amounts of elastin in their extracellular matrix, making this an ideal system for studying elastogenesis. In this study, the ability of individual cells to synthesize tropoelastin was examined by in-situ hybridization methods. One-micron semi-thin epoxy resin-embedded transverse sections of cells cultured 1, 2, 3 and 4 weeks showed an increase with time in both the number of cells with hybridization signal and the signal intensity; tropoelastin mRNA hybridization signal intensity decreased thereafter up to 8 weeks in culture. In longitudinal sections through the early cultures (1-week), we observed mitotic cells with no detectable hybridization signal, and non-mitotic cells with either no, little or high signal intensity. These data suggest that mitotic cells do not synthesize tropoelastin, and that there is a strong correlation between the hybridization signal intensity and the rate of tropoelastin synthesis. These data also suggest in-situ hybridization methods can detect which cell(s) contain tropoelastin mRNA, their location in the multilayer, and variations in signal intensity. We conclude it is possible to correlate hybridization signal intensity with variations of tropoelastin mRNA levels within individual cells of the cultured smooth muscle cell multilayer. PMID- 1435517 TI - The group A streptococcal M-type 3 protein gene exhibits a C terminus typical for class I M proteins. AB - The M protein gene (emm gene) from a reference group A streptococcal strain of serotype M3 was amplified by the polymerase chain reaction and partially sequenced. Hybridization assays using an oligonucleotide probe derived from the N terminal sequence revealed that this gene segment is highly homologous among M type 3 isolates. Of note, analysis of the nucleotide sequence data from the C terminus of the gene confirmed that the emm 3 gene exhibited all the features characteristic for group A streptococcal M-class I molecules. Recently published sequence data that were assigned to emm 3 resulted from a strain confusion and were shown to be the first one derived from an emm gene of an M-untypable isolate. PMID- 1435518 TI - Ubiquitous occurrence of virR and scpA genes in group A streptococci. AB - Until now a few serotypes of M-class I group A streptococci (GAS) have been shown to encode VirR, a positive regulatory factor for the coordinate expression of the M protein (emm) and C5a peptidase (scpA) genes. The polymerase chain reaction technique has been applied to the genomic template of 36 GAS serotypes to demonstrate the general presence of VirR (virR) genes and scpA in GAS of both M classes. A virR gene region conserved in size was demonstrated for every strain investigated. Differences between virR genes from GAS of the two M classes were mainly confined to the 3' end of the gene and a region upstream of the gene's promoter. Every M-class II strain and some M-class I isolates were shown to possess a scpA gene of 4.6 kb, the rest of the M-class I GAS harbors a 3.5-kb scpA gene. The additional segment of 1.1 kb in the large-size scpA genes was located within a region of direct repeats at the 3' end of the gene. Among the serotypes encoding a large-size scpA gene a minority exhibits additional sequence variation downstream of the region of direct repeats. PMID- 1435519 TI - Recombinant human granulocyte-macrophage colony-stimulating factor in children with chemotherapy-induced neutropenia. AB - Twenty children 1-17 (median, 5.5) years of age received GM-CSF during chemotherapy-induced neutropenia at the dose of 5 micrograms/kg/day, continued until the absolute neutrophil count (ANC) exceeded 500 x 10(6)/liter. Twelve children with solid tumors received GM-CSF after courses of conventional chemotherapy (VP-16 + ifosfamide or "6 in 1"). One course followed by GM-CSF was compared to identical courses without GM-CSF in the same patients. Eight children with recurrent/poor risk malignancies received GM-CSF after marrow-ablative therapy and autologous bone marrow transplantation (ABMT). Their engraftment data were compared to matched historical controls. In both groups GM-CSF accelerated myeloid recovery, which was preceded by the appearance of immature myeloid elements in bone marrow. The ANC levels of 200, 500, and 1,000 x 10(6)/liter were exceeded 2, 3 (P < 0.05), and 6 (P < 0.005) days earlier with GM-CSF in the conventional chemotherapy group, and 6, 10 (P < 0.05), and 9 days earlier in the ABMT group, as compared to the controls. All adverse effects observed were mild, including skin rashes, nasal stuffiness, general achiness, nausea, and fever. We conclude that GM-CSF is well tolerated in children and accelerates myeloid recovery in chemotherapy-induced neutropenia. PMID- 1435520 TI - Minimal requirements for the diagnosis, classification, and evaluation of the treatment of childhood acute lymphoblastic leukemia (ALL) in the "BFM Family" Cooperative Group. AB - Minimal requirements and their rationale for the diagnosis and the response to treatment in childhood acute lymphoblastic leukemia (ALL) were defined in the recently instituted "BFM-Family"-Group, in which the German, Austrian, Dutch, Italian, Belgian, French and Hungarian childhood leukemia study groups cooperate. ALL is defined as > or = 25% lymphoblasts in the bone marrow; for confirmation of the diagnosis and classification the criteria of the French-American-British (FAB) criteria are retained. For determination of the extent of the disease at diagnosis or relapse the criteria by the Rome Workshop [1986] are recommended: An obligatory panel of monoclonal antibodies for immunophenotyping was defined, as well as criteria for precursor B-ALL and T-ALL. Cytogenetic studies may support the diagnosis and subtyping, and are essential to identify certain patients with a high risk of treatment failure (f.i. t(9;22), t(4;11)). The role of molecular genetics for the diagnosis and the characterization of leukemia and the value of its clinical application needs further elucidation. Relapse was defined as recurrence of evident leukemia in the blood, bone marrow (> or = 25% lymphoblasts) or at any other site (to be confirmed by histological examination). Bone marrow involvement combined with extramedullary relapse was defined as > or = 5% lymphoblasts in the bone marrow. PMID- 1435521 TI - Primary skeletal non-Hodgkin's lymphoma in the pediatric age group. AB - The authors discuss rare primary skeletal non-Hodgkin's lymphoma in 16 patients treated from 1973 to 1989. The symptoms of these patients related to bone lesions in 95% of the cases. These bone lesions were monostotic or polyostotic, with or without regional and distant metastases. The locations of these lesions were long bones in 13 patients, pelvic bones in seven patients, and skull and vertebral bodies in two patients. The anatomical locations of these lesions in the bones were diaphysis alone in one patient, epiphysis in two patients, metaphysis in three patients, and a combination of diaphyseal, epiphyseal, and metaphyseal lesions in seven patients. Extraskeletal involvement was present in nine patients; extraskeletal sites included regional or distant lymph node involvement in seven cases, the mediastinum in two, lung nodules in two patients, the skin and subcutaneous regions in four patients; bone marrow in three patients, and peripheral nervous system (PNS) in one patient. Two patients had stage I disease, three had stage II disease, eight had stage III disease, and three had stage IV disease. The majority of patients had large noncleaved cell diffuse lymphomas or DHL by Rappaport classification. All patients were treated with the LSA2-L2 protocol; six patients received radiation therapy to the affected bone, and ten patients received no radiation therapy. Three patients failed on treatment within the first 4 months of therapy. Two patients developed a second tumor, one in the radiation therapy field and the other in a patient who received no radiation therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435522 TI - Primary malignant cardiac tumors: update 1992. PMID- 1435523 TI - Recurrent cerebrovascular accident with L-asparaginase rechallenge. AB - We report a 15-year-old boy diagnosed with acute lymphoblastic leukemia (ALL) in 1983. Induction therapy included L-asparaginase. After the second dose of L asparaginase, he had a left sided focal seizure and computed tomography (CT) scan of the head showed a right frontal infarct. No further L-asparaginase was given. Complete remission was achieved and he successfully completed therapy in 1986. Eight months later he had an isolated bone marrow relapse. Reinduction therapy included L-asparaginase. After the fourth dose of L-asparaginase, he presented with severe headache and a CT scan showed a right temporal infarct. Repeat infarction on rechallenge with L-asparaginase has not been previously reported. Prophylactic therapy, such as fresh frozen plasma, should be considered before patients, with a previous cerebral insult, are rechallenged with L-asparaginase. However the effectiveness of such therapy has not been established. PMID- 1435524 TI - [The characteristics of the intrathoracic complications of suppurating echinococcal liver cysts]. AB - Using the material from 48 patients with intrathoracic complicated festered liver echinococcus cysts, the variations of break and the localization of connections between festered liver echinococcus cysts and thoracic organs were characterized. The pathological processes in the organs of the pleural cavity were described. A classification of intrathoracic complications proposed by the authors permits one to avoid diagnostical and tactical mistakes and to decrease human mortality. PMID- 1435525 TI - [The characteristics of the clinical course of hydatid pulmonary echinococcosis in the native inhabitants of Chukotka]. AB - 23 patients with pulmonary hydatid disease were observed in Chukotka. The patients observed were divided into 2 groups (14 and 9 patients) matched for sex, age, invasion intensity and topography. The patients of the first group were operated after they had been diagnosed, and the patients of the second group were observed without operation. In the both groups, the symptoms of invasion were low expressive, its course was torpid, the complications were rare and the dissemination was not recorded. Two patients observed without operation recovered after the break of the cyst into the bronchus and its evacuation. Relapses of invasion after operation were not recorded in any case. The causes of the good clinical course of pulmonary hydatid disease in the aborigines of Chukotka and the necessity of revising the treatment course are discussed. PMID- 1435526 TI - [Natural foci of trichinelliasis in the Caspian Sea area]. AB - The formation of natural foci of trichinelliasis was shown to depend on the established biocenotic relations between carnivorous animals. A highly intensive transmission of the invasion was recorded in continental areas where predators suffer from the lack of food in winter. Identification of the isolated Trichinella samples using single-pair cross hybridization and isoenzyme identification methods showed that the parasites of predators are T. spiralis nativa on the Northern Caspian coast and T. s. nelsoni on the Southern coast. PMID- 1435527 TI - [Trichinelliasis in the wild and domestic animals of Kamchatka Province]. AB - The results of many years' observations and literature data allowed one to determine the species of wild and domestic mammalians, vectors of trichinelliasis in Kamchatka. The variability of trichinelliasis prevalence in individual mammalian species were found in relation to their habitation place. Significant fluctuations of the index are presented by years. Cases of trichinelliasis in wild American minks (acclimatized species) and in pigs were noted. PMID- 1435528 TI - [Trichinelliasis in southern Ukraine]. AB - The analysis of literature data and the authors' own investigations showed that the southern part of the Ukraine is a trichinelliasis endemic territory where the synanthropic foci of the invasion are registered. The wide spreading of trichinelliasis among pigs and the nonobservance of the control measures provided by the veterinary legislation cause an increase in human prevalence. PMID- 1435529 TI - [A morphometric study of the bone marrow of mice infected with Trichinella spiralis and T. pseudospiralis]. AB - The study of cytograms of the marrow of mice with experimental T. spiralis and T. pseudospiralis invasion of 1 to 60 days revealed the marked activation of granulocytes and lymphoid cell proliferation with the much lower response of erythroid cells. The maximal response occurred at 21-35 days of invasion with subsequent diminution. In mice experimentally invaded with T. pseudospiralis the response of the marrow was less pronounced, but the period of active cell proliferation was prolonged. PMID- 1435530 TI - [Intestinal trematodiases (metagonimiasis, nanophyetiasis): clinico parasitological research and the first trial of using Azinox in a focus of the lower Amur River valley]. AB - A focus of metagonimiasis and nanophyetiasis is described with the average human prevalence of 66.7 and 4.2%, respectively and low intensity of invasions (less than 100 eggs per 1 g). Metagonimiasis and nanophyetiasis are clinically expressed as chronic enterocolitis. A high effect of a single dose 10 mg/kg of azinox against metagonimiasis (98%) and nanophyetiasis (100%) was shown. The treatment course was proved to be useful in the foci of the Amur basin. PMID- 1435531 TI - [The role of national meat dishes in infecting the population of Azerbaijan with taeniarhynchiasis]. AB - The survival of taeniorhynchus cysticerci in 12 national meat dishes was studied in Azerbaijan. It was shown that in 7 dishes (sulu hinghal, suzma hinghal, kutab, gyurza, dushbara, dolma, tavah-kebob) the cysticerci died at suitable temperature and continuous cookery treatment. But in the mutton roasted on spits, lulah kabob, kyufta, kutaby and some other dishes 5.7 to 82% of cysticerci survive, and the dishes might be a danger as factors of transmission. PMID- 1435532 TI - [A sanitary helminthological assessment of different methods of salting fish in the Vyatka and Kama River basins]. PMID- 1435533 TI - [The infectivity of the population with the tapeworm Diphyllobothrium klebanovskii in an area of infection drift in the Khabarovsk Territory]. AB - Copro-ovoscopic survey of the human population in the Khabarovsk Territory and the analysis of data of account of territorial sanitary epidemiological station showed that people invaded with D. klebanovskii are registered only in areas whose rivers catadromous salmon come to spawn. Most of invaded people are recorded on the seashore. The risk of tapeworm invasion and the epidemiological characteristics of the carry-over zone are discussed. PMID- 1435534 TI - [The search for new antiparasitic agents. 11. The acute toxicity and anticestodal activity of the new anthelmintic Tizanox compared with Azinox]. AB - A synthesis is described and the results of toxicological trial of the potential anthelmintic agent G-1587 are presented. The agent is 2-(cyclohexylcarbonyl) 1,2,3,6,7,11b-hexahydro-2H-[1, 2,5] thiadiazino [3,2-a] isoquinoline-4,4-dioxide. The agent was shown to have a low toxicity, the maximal sublethal dose for mice being 4.0 g/kg when given per os. PMID- 1435535 TI - [The comparative efficacy of medamine and Vermox in enterobiasis]. PMID- 1435536 TI - [An improved complex of measures to prevent enterobiasis]. AB - Enterobiasis is the most common helminth in the USSR. Despite of its clinical manifestations in children, some parents do not see a doctor. 105 parents were interrogated by questionnaires. 71% of them called the reason why they had taken no medical advice and the rest evaded the question. The parents' questionnaire is an important measure for preventing and controlling enterobiasis with regard to better health education methods used in the work with parents and tutors from pediatric institutions. PMID- 1435537 TI - [The sanitary-epidemiological assessment of the enterobiasis situation and its prevention in children's institutions in new buildings]. AB - A complex plan of enterobiasis control measures for a sharp and stable decrease of the prevalence level at nursery schools in new buildings is presented. This complex plan allows one to reduce the extent of investigations 3-4-fold. A trial of the complex plan proposed on territories with foci of different types should be expedient with its subsequent introduction into the practice. PMID- 1435538 TI - [The epidemiological efficacy of the chemoprophylaxis of zoonotic cutaneous leishmaniasis in rural inhabitants]. PMID- 1435539 TI - [Enzymes of the peripheral blood leukocytes from the vertebrate host in an experimental Leishmania infection. 1. Neutrophil acid phosphatase]. AB - The results of cytochemical identification of acid phosphatase in the neutrophils of mice, guinea pigs and golden hamsters inoculated with leishmanial promastigotes of different species and virulence and also of people vaccinated against zoonotic cutaneous leishmaniasis are presented. The reversible increase of the enzyme activity in host's blood neutrophils and its dependence on parasite species and virulence are shown. PMID- 1435540 TI - [The serological examination of the population for leishmaniasis and the detection of Leishmania in rodents in the Republic of Guinea]. AB - A serological study on leishmaniasis in human population of Guinea revealed the percentage of seropositive persons varying in different parts of the country from 0.84 to 4.76 (according to C-ELISA) and from 1.0 to 5.1 (according to IFAT). The majority of sera positively reacting in C-ELISA with the antigen of Leishmania major in dilutions of 1:800 and higher were received from Kundara District (northwestern part of the country), and with the antigen of L. donovani sensu lato from Sigiri and Kankan districts (northeastern part of the country). All the districts were situated in the savanna zone. The amastigotes of Leishmania were found in the liver and spleen of Tatera gambiana caught near Kindia. These data suggest the circulation of Leishmania over the territory of Guinea. PMID- 1435541 TI - [The surveillance of anthropogenic influence on the environment in intestinal parasitoses]. AB - The necessity of anthropogenic influence control system as a component of the system of antiparasitic measures is proved. "System of anthropogenic influence control" proposed by the authors includes the complex of juridical and scientific methodological supply, the subsystem of sanitary parasitological monitoring, the subsystem of measures for environmental protection and sanitation and laboratory control. The use of the system in practice might allow one to increase the efficacy of environmental protection and parasitic disease prophylaxis measures. PMID- 1435542 TI - [Balantidiasis]. PMID- 1435543 TI - [The localization of Trichinella antigens, their molecular biological characteristics and the methods for their isolation]. PMID- 1435544 TI - [Grain itch]. PMID- 1435545 TI - [The tasks of epidemiological health stations in organizing ecologically safe measures to control the vectors of transmissible diseases]. PMID- 1435546 TI - [The clinico-immunological characteristics of the mixed pathology of tuberculosis and clonorchiasis in endemic areas of Khabarovsk Territory]. PMID- 1435547 TI - [The division of the territory of Azerbaijan into districts by hydatid echinococcosis]. AB - The epizootiological and epidemiological stratification of the territory of Azerbaijan on hydatid disease was made. Four zones were identified as low, moderately, highly and extremely endemic. These zones are differentiated from their climatic and social conditions for echinococcosis distribution, human incidence and prevalence, canine and ovine number and prevalence, and the time of survival of echinococcus eggs in the soil. The most intensive disease control measures are recommended in mountainous regions of the Small Caucasus. PMID- 1435548 TI - [Antibody detection in zoonotic cutaneous leishmaniasis by using the indirect immunofluorescence reaction and C-ELISA in different clinical manifestations of the disease]. AB - 189 sera from patients with ZCL of different stages were studied by means of RNIF and C-ELISA. A high significant correlation between RNIF and C-ELISA indices was shown, but the latter test was proved to be more sensitive and therefore more effective. In patients with ZCL, a significant direct correlation between the duration of the process and the antibody titer was established by means of C ELISA. In patients with ZCL at the third (final) stage (reduction and granulation of lesions), the C-ELISA liter of specific antibodies was higher than at the second stage (rapidly progressing ulceration of lesions). The findings indicate the presence of clinical and serological parallels in ZCL and show it expedient to compare the dynamics of antibody genesis and cell immunity indices in further studies. PMID- 1435549 TI - [The variability of the itch mite Sarcoptes scabiei De Geer (Acariformes, Sarcoptidae) in connection with the epidemiology of scabies. A rank system for the variability of the chaetoid integument in females]. AB - The variability of the naked section of the chaetoid cover of itch mite Sarcoptes scabiei De Geer females was studied. The sample used was divided into 5 grades by the number of undeveloped chaetoids. The structures surrounding the naked section, its size and dimensions of the female body were analysed in each grade of specimens. Such grade scale for describing the chaetoid cover proved to be useful for comparative analysis of human and animal forms of itch mite. PMID- 1435550 TI - [The importation of malaria from Afghanistan into the USSR (a retrospective analysis of data from epidemiological surveys of cases and foci during 1981 1990)]. AB - A retrospective analysis of imported malaria due to military operations revealed the main regularities in the behaviour of Plasmodium vivax population and the relationships between the imported parasite and the native Anopheles species. High percentage of cases with protracted incubation was noted in soldiers after their home-coming; the clinical symptoms were often registered 7-12 months after return. No epidemic consequence of imported and introduced cases of tertian malaria in malariogenic areas was shown. The effect of mass drug administration in military contingents was proved to be low due to irregular use of drugs or their discontinuance. The import of carriers to malariogenic areas was found to cause a minimal risk of restoration and implantation of tertian malaria. The current epidemiological monitoring system was shown to be rather effective for maintaining the epidemiological prosperity in the country. PMID- 1435551 TI - [The feeding characteristics of mosquito larvae of the genus Anopheles]. AB - Studies carried out on 6 species of malaria mosquitos revealed a relationship between the larval activity to scratch the substrate and their morphological and physiological features and also their development at different depth of feed immersion. The development of scratching capacity was compared in different species of Anopheles and Cellia subgenera. PMID- 1435552 TI - [Observations on malaria vectors in Mozambique. I. The status of Anopheles populations before the start of mosquito control]. AB - The basic status parameters of populations of the main malaria vectors (Anopheles arabiensis and An. funestus) in the vicinity of the city of Maputo, Mozambique, were considered, such as mosquito density and its seasonal variation, female biting activity rate, degree of mosquito-man contact, degree of exophilia and endophagy, physiological age of females, duration of gonotrophic cycle, sporozoite index, vectorial capacity, entomological inoculation rate. PMID- 1435553 TI - [The relation between the mode of feeding of malarial mosquito larvae and their resistance to bacterial insecticides]. PMID- 1435554 TI - [A trial of the possible joint use of mermithids and bacterial preparations for the control of mosquito larvae]. AB - The action of bacterial insecticides based on Bacillus thuringiensis H-14 and B. sphaericus in a dose of 0.005-2 mg/l on the mermithids Romanomermis iyengari, R. culicivorax and R. jingdeensis was studied. It was shown that though bacterial agents suppressed mermithid preparasite larvae density about 30-40%, the survivors might invade 100% of mosquito larvae. The viability and fertility of adult mermithids did not change under the influence of bactoculicide in doses 5 50 times higher than those used against mosquitoes in practice. In combined field trials of sphaerolarvicide (1.5 kg/ha) and R. iyengari mermithids the infectivity of Anopheles sacharovi larvae reached 96%. Mermithids in combination with bactoculicide and sphaerolarvicide might be useful in integrated control systems because these bacterial agents are harmless for mermithids of all stages in doses useful against mosquito larvae. PMID- 1435555 TI - [Insecticide resistance and irritability of Culex pipiens in Moscow]. AB - Resistance and irritability to permethrin, deltamethrin, bendiocarb, propoxur, fenitrothion, malathion, dieldrin and DDT (WHO standard papers) were determined in Culex pipiens collected in the basements of big houses in the centre of Moscow. Mosquitos were found to be moderately resistant to fenitrothion (87% mortality), DDT (83%) and propoxur (80%), and susceptible to the remaining insecticides. The irritability was low to dieldrin but moderate to permethrin, propoxur and DDT, and high to the rest. The irritability to bendiocarb seems to be really caused by the repellent action of citric acid which the WHO standard paper is impregnated with. It is recommended to use pyrethroids against mosquito larvae and pyrethroid brickets against adults. PMID- 1435556 TI - [The point-scale assessment of the intensity of the possible contamination by helminth eggs of large reservoirs in the Volga basin]. AB - Possibility for the contamination of man-made lakes by helminth eggs caused by superficial drain was estimated. The estimation allowed one to apply a differential approach to the organization of protection measures. PMID- 1435557 TI - [The clinico-immunological characteristics of hymenolepiasis]. AB - Clinical manifestations were observed only 16 out of 61 patients aged 15-32 years who had hymenolepiasis. Despite their degree, there was impaired dexylose absorption, lower serum lysozyme activity and higher serum complement activity, depressed immunological reactivity parameters (the count of T- and B-lymphocytes, their functional activity), decreased IgA titer and increased IgE titer in the sera in all the patients observed. Six months after the effective dehelminthization, varying immunodepression still remained in all the convalescents. There types of restoration of immunological reactivity were identified: torpid, reactive and highly reactive. The torpid type was significantly more frequently observed in patients with subclinical (asymptomatic) hymenolepiasis course than in patients with its clinical manifestation. PMID- 1435558 TI - [Opisthorchiasis as a component in a mixed infection]. AB - A survey of the same human contingents (children under 14 years and adults) in different zones of Ukraine revealed the opisthorchiasis foci of different intensity in the northeastern part of Polesye and in the forest-steppe zone. The affliction of adults ranged from 27.5 +/- 2.2% to 2.8 +/- 0.7%, that of children was from 14.5 +/- 2.3% to 0. In the foci of high and moderate tension, the trichocephaliasis prevalence was 10.2 +/- 0.7%, ascaridiasis 5.1 +/- 0.5%, amebiasis 2.4 +/- 0.7%, lambliasis 7.7 +/- 0.6%, and outside the foci these figures were lower (2.0 +/- 0.7%; 2.4 +/- 0.7%; 0.5 +/- 0.3%; 2.9 +/- 0.8%, respectively). In concurrent invasions and infections, the number of helminth eggs and protozoan cysts excreted by patients was significantly lower than in that in monoinvasion. PMID- 1435559 TI - [The epidemiological characteristics of diphyllobothriasis caused by Diphyllobothrium klebanovskii in the Amur River basin]. AB - The diphyllobothriasis incidence in the workers of the Amur basin steamship company during 1980-1989 was studied. This rate was shown to be more than 6 times than that of other population (68.7 and 10.4 case per 100,000 person, respectively). The role of the workers of the company in the circulation of the invasion and prophylactic measures in the region were discussed. PMID- 1435560 TI - [The morphological changes in the organs of the lymphoid system in the experimental infection of mice with Trichinella spiralis]. AB - The dynamics of morphological changes in central and peripheral organs of the lymphoid system of mice experimentally invaded with Trichinella spiralis was studied. The immune response of the host was shown to have two phases including two peaks and the suppression period. The activation of the lymphoid organs was observed in earlier intestinal and muscular phases, and the suppression was noted in migration phase of invasion. PMID- 1435561 TI - [Sanitary parasitocenology. The subject, goals and tasks]. AB - The necessity for developing a new parasitological discipline, such as sanitary parasitocenology, is evidenced. Training of specialists with a wide range of parasitological knowledge and goal-oriented complexation of the investigations of parasitologists of different profile are shown to be required. The necessity for elaborating the measures for disinfection of environmental objects is shown taking into account the degree of pathogenicity of each parasitocenosis. PMID- 1435562 TI - [Group cryptosporidiosis morbidity in children]. AB - The group morbidity with cryptosporidiosis (13 cases) was recorded in infants from a somatic hospital and a nursery school and also among unorganized groups. The factor of transmission was kefir prepared in the nursery milk kitchen. Cryptosporidian oocysts were not found in the personnel of the kitchen. It was supposed that the contamination of milk by oocysts occurred on milk farm. Single oocysts were found in milk sediments on the filter taken from a tank at a milk factory. PMID- 1435563 TI - [The transformation of the saprotrophic mycelial form of the fungus Paecilomyces variotii into the tissue parasitic form and its morphological characteristics]. AB - The fungus Paecilomyces variotii is known to develop as a saprotrophic mycelial form in the soil. When penetrating into the human organism or placing into a medium containing cultured cells it transforms into a parasitic flesh form. This form of the fungus was shown to undergo 3 morphological stages: endospore, juvenile (intermediate) form and mature sphaerula. The transformation of the mycelial form into parasitic one occurs in the biological media containing cells of the host, inside or outside the cell. The morphological structure of mycelium of P. variotii developed from the flesh parasitic form is different in aerobic and anaerobic conditions. In the former case, the spore production takes place by means of phialides, and in the latter case it occurs inside the mycelium. PMID- 1435564 TI - [The characteristics of the economic loss from actinomycosis]. PMID- 1435565 TI - [The efficacy of pyrantel in vulvovaginitis of enterobiasis etiology]. PMID- 1435566 TI - [A case of pulmonary aspergillosis with the formation of mycetomas in a patient with acute leukemia]. AB - The clinical and diagnostic features of fungal infection in hemoblastosis are discussed. It is shown that the adequate and early treatment allows the life threatening complication to be managed. PMID- 1435567 TI - [The sensitivity of malarial mosquitoes to DDT and malathion in the southern European part of Russia]. PMID- 1435568 TI - [The morphological changes in the small intestine of cats with metagonimiasis]. PMID- 1435569 TI - [The ascariasis and toxocariasis situation in the city of Rudnyi]. PMID- 1435570 TI - [Cyclic changes in the population count of the taiga tick in the Stolby preserve]. AB - A harmonic analysis was carried out of Ixodes persulcatus density dynamics over 33 years and the analysis of small mammal density and some climatic factors. It was found that the chronological changes of all the three processes contained cyclic components with the period 5.5 and 11; 3-4; 5.5 and 14-16 years, respectively. A long-term prognosis of I. persulcatus density was made based on harmonic synthesis. PMID- 1435571 TI - [The clinico-parasitological examination of a focus of intestinal nematodiases in Ha-Shon-Bin Province in the People's Republic of Vietnam and an analysis of 5 medamine treatment schemes]. AB - An intensive focus of intestinal nematodiases in a foothill province of Vietnam is described; the incidence of ascaridiasis there was found to be 81.8%, trichuriasis 78.1%, and ankylostomiasis 12.3%. Polyinvasions were detected in more than 80% of the examinees. Analysis of five schemes of medamin therapy, used in three provinces in 595 patients with ascaridiasis, 490 ones with trichuriasis, and 323 ones with ankylostomiasis has shown that the treatment efficacy was reducing with the invasion intensity augmentation. In ascariasis the 3- and 5-day therapeutic schemes were the most effective, their efficacies being 68.4 and 82.0%, respectively; in trichuriasis and ankylostomiasis a 3-day scheme was the best, its efficacies being 74.0 and 71.9%, respectively. Retrograde ascarid migration occurred in 1.2% of 595 ascaridiasis patients after medamin therapy. PMID- 1435572 TI - [A clinico-epidemiological study of opisthorchiasis in the Altai Territory]. AB - Eighty-eight patients with opisthorchiasis were treated with biltricide in an anthropurgic and natural focus of opisthorchiasis in the Altai Territory. A one day course of drug therapy, in a total dose of 60 mg/kg, was administered. Forty two patients developed side effects in the course of therapy. Complete elimination of the helminths was achieved in 83 (94.3 +/- 2.3%; p less than 0.05) patients in 6 months after therapy. PMID- 1435573 TI - [The dynamics of the indices of opisthorchiasis invasion of the population of the Chulym River basin]. AB - Based on the findings of a 20-year follow-up, the authors analyze the incidence of opisthorchiasis in one of the regions of the Krasnoyarsk Territory, the Chulym River region. They analyze the time course of the major parameters, i.e. incidence rate, absolute and relative increment of this value and the significance of a 1% increment as exemplified by this region. They emphasize that a complex of sanitary and hygienic measures should be implemented to control and prevent opisthorchiasis in this region. PMID- 1435574 TI - [The effect of specific therapy on the bone marrow reaction in experimental trichinelliasis]. PMID- 1435575 TI - [Bloodsucking mosquitoes on the irrigated lands of Kara-Kalpakia. 2. The annual cycle of Anopheles pulcherrimus]. AB - The authors characterize the annual cycle of An. pulcherrimus population, distinguish the stages of this cycle that differ by the population composition and number and by the size of its area. The spatial structure of the population depends on the site of water bodies for wintering and the conditions at different territories. High numbers of mosquitoes were found in the southern part of the oasis at villages of rice-growing farmers. Mosquito population densities in the central parts of the oasis are much lower and are increased nearby sandy islets. PMID- 1435576 TI - [The susceptibility of mosquitoes for Plasmodium gallinaceum in the joint use of biologically active substances]. AB - Making use of a model pair Aedes aegypti--Plasmodium gallinaceum, the authors assess the susceptibility of mosquito female survivors to malaria agent after treatment of larvae with various bioactive substances. Eight binary combinations of 6 preparations have been tried: dimilin and uvemon, insect development regulators; fundosol and copper sulfate, fungicides; phytobacteriomicin (PBM), a larvicidal antibiotic; bactoculicide, a bacterial agent. Combinations of PBM with compounds differing by their mechanisms of action were found to inhibit the specific effect of PBM on the vector, PBM specific effect consisting in depression of mosquito susceptibility to P. gallinaceum. PBM combinations with some agents may alter other parameters of the vector potential: combinations of copper sulfate or uvemon with low concentrations of PBM potentiated the larvicidal effect, and PBM mixtures with fungicides reduces the activity of female attacks. PMID- 1435577 TI - [The spread of Phlebotomus papatasi Scop., 1786 through the territory of Central Asia and southern Kazakhstan]. AB - The data on distribution of the main vector of zoonotic cutaneous leishmaniasis (ZCL) Phlebotomus papatasi through Central Asia and southern Kazakhstan are presented. The highest indices of density of this species (100 and more specimen per stick trap) were observed only in the Tejen oasis, rather high ones (1-10, 10 100) in the river valleys and at the foothill, and the lowest one (0.01-0.1)- over the desert territory where ZCL was not practically found. Using these data 2 maps were prepared. The first map shows the pattern of Ph. papatasi geographical distribution with the use of a relative density index. This map can be useful for determining ZCL danger in areas where Ph. papatasi occurs. The second indicates sandfly distribution over Karshi steppe territory the where Ph. papatasi density depends on soil moisture. This map can serve as a model for forecasting Ph. papatasi density under anthropogenic influence. PMID- 1435578 TI - [Ixodid ticks in the mountainous part of the Crimea]. AB - About a hundred of patients with tick-borne encephalitis (TBE) were recorded over the latest decade in the Crimea, and 60 TBE virus strains were isolated from the ticks collected on the peninsula. The results of studies carried out in 1986-1990 helped define the borders of 4 local natural foci of TBE, study their acarifauna, detect the principal TBE vector--Ixodes ricinus (with a mean virophority of 0.6%), and distinguish two foci with a combination of TBE and Crimean-Congo hemorrhagic fever. PMID- 1435579 TI - [The participation of birds in the circulation of the tick-borne encephalitis virus in the Asian part of Russia. 1. Natural foci in the Far East]. AB - Virologic examinations of 811 samples of 70 species and of 81 ova from layings of 11 bird species, carried out in natural foci of tick-borne encephalitis (TBE) in the southern Maritime [correction of Primorye] Territory, yielded negative results; serologic examinations revealed a low level of the immune stratum to TBE virus even in the birds feeding on the soil or on grass and shrubberies, that is, belonging to the first and second ecologic groups (0.8 +/- 0.4%). A difference has been demonstrated between the shares of TBE immune samples in the first and second+third (birds feeding on trees but sometimes on soil) +fourth (feeding on trees, in air, out of forests, on animals) ecological groups of birds, as well as between the first+second and third+fourth groups. PMID- 1435580 TI - [The age-related structure of an Ixodes ricinus population studied by using a rapid anatomical method]. AB - A rapid anatomic method for the assessment of the physiologic age of ticks and their virtual age was used in studies of the age structure of a natural population of I. ricinus in the Moscow region. The anatomic method was found quite fit for the purpose. The findings evidence that the age structure of I. ricinus (active imago) population is heterogeneous with variously directed seasonal fluctuations. In spring the structure is the youngest (up to 60% of imagoes are in the second age, 8 months) and in the fall the females are mainly old, just starting to get younger (up to 90% are in the third and fourth ages, that is, aged a year). The structure is liable to changes with seasons and years. Geographic differences in the age structures were revealed: in the fall the Moscow region population is generally older than that of the St. Petersburg region. The anatomic method widens the potentialities of studying the age structure of the populations of tick-borne encephalitis vectors. PMID- 1435581 TI - [The sensitivity of the tick Ornithodoros papillipes Bir. to Icon]. AB - Laboratory trials have demonstrated a high and stable acaricidal activity of aikon towards O. papillipes ticks. The minimal dose (on filter paper) of aikon providing a 100% death of the ticks at all developmental phases, effective for at least 9-12 months, was 30 mg/m2. In exposure to this dose the ticks died within 1 7 days; if impregnated filter paper was stored for a long time, within 15-30 days. The lower the dose was, the slower the effect and lesser the total death rate of the ticks were. PMID- 1435582 TI - [Blastocystis infection and AIDS]. PMID- 1435583 TI - [The characteristics of cryptosporidiosis prevalence in Nizhni Novgorod Province]. AB - A total of 4070 patients with acute intestinal diseases were tested for cryptosporidiosis in 1989, 1806 of these without diarrhea (controls), 286 of them working at slaughter houses, milk-packing plants and dairy plants, 192 subjects with a history of contacts with cryptosporidiosis patients in the focus of the disease, and 7 animals. Cryptosporidiosis was responsible for 3.2% of acute intestinal conditions in children; cryptosporidia oocysts were not detected in adults or healthy subjects. The high risk group invasion has made up 2.7%. Two cases of the invasion were detected among subjects with a history of contacts with cryptosporidiosis patients, this making up 1.04%, none of them presenting with any clinical symptoms of the invasion. PMID- 1435584 TI - [The microstructure of trematodes studied by electron microscopy]. AB - The main tendencies in the studies into the ultrastructure of trematodes (including species of medical importance) using scanning and transmission electron microscopy are considered. Attention was paid to disproportions in the studies into the different developmental stages of trematodes: maritae are better studied than parthenogenetic and larval stages and especially eggs and miracidia. During the last years the number of studies using the complex of histochemical, radioisotope and electron microscopic methods is increasing, among them the investigations on the changes caused by modern anthelmintic agents in the tegument and viscera of trematodes. These are mainly the trematodes of Schistosomatidae, Echinostomatidae, Fasciolidae and Paragonimidae families that were studied by electron microscopy, and the studies on Opisthorchidae are very scarce. PMID- 1435585 TI - [The optimization of a method for determining the insecticidal activity of bacterial preparations vis-a-vis mosquito larvae]. PMID- 1435586 TI - [The efficacy of a new insecticide ethofenprox (Trebon) for controlling different types of insects]. AB - The insecticidal action of the new compound ethofenprox (trebon) in the form of 10 and 30% flow concentrate against house flies, cockroaches, bed bugs, rat fleas, mosquito imagines and larvae of Aedes and Culex genera was studied in the laboratory and in the field. The effective doses and the methods of spraying were established. 10% flow trebon is allowed by the USSR Ministry of Health to be useful in medical disinfection. PMID- 1435587 TI - [The dynamics of enterobiasis infection in children's collectives]. PMID- 1435588 TI - [A negative result in infecting piglets with Enterobius vermicularis against a background of glucocorticoids]. PMID- 1435589 TI - [F. Efremov--a Bukhara slave and traveler of the 18th century--author of a helminthological treatise on dracunculosis]. PMID- 1435590 TI - [Clonorchiasis in the People's Republic of Vietnam. 2. The clinico parasitological examination of a focus and a trial of prazinquantel treatment]. AB - Examinations of 1599 residents of a polyinvasion focus at a seaside province Ha Nam Nin, Vietnam, have revealed clonorchiasis in approximately 13.9% of the examinees; in subjects aged over 30 this value was 29.3%. Factors conducive to a lower incidence of clonorchiasis were detected, among them a moderate intensity of the invasion: the mean arithmetic was 1419 +/- 306 eggs/g, the mean geometric 673 egg/g, as shown by the Kato-Kats' technique. Analysis of five therapeutic schemes used in clonorchiasis, making use of chloxilin, medamin or praziquantel, has demonstrated a low efficacy of all of them. Praziquantel therapy in a daily dose of 25 mg/kg for 2 days was found the most effective (52%), being conducive to a reduction of the invasion intensity by at least 90%. Such therapy was associated with a high incidence of side effects (91.2%), this ruling out a higher dosage. PMID- 1435591 TI - Backscatter coefficient imaging using a clinical scanner. AB - A clinical ultrasound scanner has been integrated with a digital data acquisition system to record echo signals for off-line processing of quantitative acoustic backscatter images. The method used to determine backscatter coefficients accounts for experimental factors related to the beam directivity function, the transmitting and receiving electronics, and the attenuation path of the beam. After characterization and calibration of the ultrasound scanner according to the data processing requirements, the quantitative backscatter coefficient for tissue mimicking phantoms are within 14% of a value predicted by scattering theory. On five normal volunteers, preliminary in vivo liver images of the acoustic backscatter coefficient are obtained. Results from this study are compared to previously published in vitro results. PMID- 1435592 TI - Image feature analysis and computer-aided diagnosis in digital radiography: automated detection of pneumothorax in chest images. AB - In order to aid radiologists in the diagnosis of pneumothorax from chest radiographs, an automated method for detection of subtle pneumothorax is being developed. The computerized method is based on the detection of a fine curved line pattern, which is a unique feature of radiographic findings of pneumothorax. Initially, regions of interest (ROIs) are determined in each upper lung area, where subtle pneumothoraces commonly appear. The pneumothorax pattern is enhanced by the selection of edge gradients within a limited range of orientations. Rib edges included in this edge-enhanced image are removed, based on the locations of posterior ribs that are determined separately. A subtle curved line due to pneumothorax is then detected by means of the Hough transform. The detected pneumothorax pattern is marked on the chest image displayed on a CRT monitor. With the present computer method applied to 50 chest images (28 normals and 22 abnormals with pneumothorax), we were able to detect 77% of pneumothoraces, with 0.44 false-positives per image. PMID- 1435593 TI - Highly stable solid-state x-ray detector array. AB - A detailed analysis of the effects of temperature changes, over time and between array elements, on the generation of circular artifacts in images produced by x ray computed tomography was reported. We give formulas for calculating--according to the x-ray energy, detector sensitivity, and observed image quality (contrast and spatial resolution)--the maximum offset temperature coefficient and maximum gain temperature coefficient that will allow circular-artifact-free imaging. A temperature-controlled and insulated solid-state x-ray detector array, consisting of Gd2O2S:Pr,Ce,F ceramic scintillators coupled to crystal Si pin-photodiodes and designed to meet the requirements for these coefficients, produced high resolution artifacts-free CT images of a phantom head. PMID- 1435594 TI - Contrast-detail curves for liver CT. AB - Contrast-detail curves were constructed for liver computed tomographic (CT) images using an objective method. Stimuli were created by superimposing disks at specified locations on sets of 92 normal liver CT images. Bright and dark disks of 9 sizes and 36 possible image contrasts were used. Sets of 92 stimuli were rendered on film at five window widths (64, 128, 256, 512, and 1024 HU). The contrast-detail (CD) curve flattened substantially for disks larger than 7-mm diameter, and its slope (on a log-log plot) was less than predicted from signal detection theory. Manipulation of display window manipulation had little impact on this disks' visibility. The results indicate that human observers have difficulty visualizing large, low-contrast details on liver CT scans, and suggest that narrowing the display window will have little effect on this limitation. PMID- 1435595 TI - Application of the EM algorithm to radiographic images. AB - The expectation maximization (EM) algorithm has received considerable attention in the area of positron emitted tomography (PET) as a restoration and reconstruction technique. In this paper, the restoration capabilities of the EM algorithm when applied to radiographic images is investigated. This application does not involve reconstruction. The performance of the EM algorithm is quantitatively evaluated using a "perceived" signal-to-noise ratio (SNR) as the image quality metric. This perceived SNR is based on statistical decision theory and includes both the observer's visual response function and a noise component internal to the eye-brain system. For a variety of processing parameters, the relative SNR (ratio of the processed SNR to the original SNR) is calculated and used as a metric to compare quantitatively the effects of the EM algorithm with two other image enhancement techniques: global contrast enhancement (windowing) and unsharp mask filtering. The results suggest that the EM algorithm's performance is superior when compared to unsharp mask filtering and global contrast enhancement for radiographic images which contain objects smaller than 4 mm. PMID- 1435596 TI - Region of interest fluoroscopy. AB - In some medical imaging applications, it is necessary to visualize only the center of the field of view with optimal quality. For example, often in interventional radiographic procedures only the region directly adjacent to the catheter tip must be well seen. A new imaging approach which reduces the number of photons exposing the patient outside a region of interest (ROI), while allowing the photon fluence to be maintained or increased in the ROI, may make more optimal use of the total integral radiation dose to the patient as well as enable increased contrast and reduced artifacts in the ROI. A demonstration is given with an angiographic phantom, for an ROI which is less than 10% of the total field of view and where the periphery receives 6% of the ROI exposure. Contrast is improved about 30% in the ROI, and yet the images are adequate in the periphery for visualizing high contrast reference features while there is a reduction in total integral patient dose. Details of the technique are discussed along with requirements for clinical implementation. PMID- 1435597 TI - Some noise properties of 2DFT MR images from asymmetrically sampled data. AB - This report describes noise statistics in 2DFT MR images, expanding the earlier work of Henkelman and others to include variably asymmetric sampling and conjugate synthesis reconstruction. The effects of low-order polynomial and Fourier phase correction used with conjugate synthesis are also explicitly considered. This analysis shows that complex images obtained by conjugate synthesis have an elliptical noise distribution, with the smaller axis corresponding to the imaginary image channel. Derivations and simulations predict a ratio of mean to standard deviation in the background of magnitude images varying from the known value of square root of pi/(4 - pi) (approximately 1.91) for full symmetry to square root of 2/(pi - 2) (approximately 1.32) at fully asymmetric or half-echo sampling; these predictions are validated over a range of asymmetry by experimental measurements. These results are important for predicting and interpreting image noise when using asymmetric sampling. PMID- 1435598 TI - Mammography screen-film selection: individual facility testing technique. AB - Variations in tube output, film processing, and radiologist's preferences affect the screen-film combination that is appropriate for any particular mammographic facility. A technique to test a variety of screen-film combinations for screening mammography is described. Films are selected for testing because of their densitometric characteristics. Dose and clinical reliability are established with phantoms before the screen-film combinations are used to image consecutive patients having bilateral examinations. The mammograms selected for evaluation are those with similar optical density ranges, and which also may be compared to available previous mammograms or which have unusual mammographic findings. All radiologists reading mammograms at a facility independently score the selected cases. Scores of "unacceptable," "acceptable," or "outstanding" are assigned to four basic imaging characteristics: sharpness, contrast, visibility of skin line, and noise. Interobserver variations by this method require normalization, unlike ROC analysis which is not applicable for this data because of the absence of proved pathologic diagnoses. The testing of 5 films and two screens using 42 patient examinations required 2 h of time from each radiologist. It took 7 h of the physicist's time to pretest the 5 films, select the 42 acceptable examinations for testing by the radiologists, and summarize the data. PMID- 1435599 TI - Analysis of contributing factors to the occurrence of off-focus radiation (OFR). AB - Off-focus radiation (OFR) has previously been described by many investigators [R. Thoraeus, Acta Radiologica 18, 753 (1937); L. Mallet and R. Maurin, Radiology 48, 628-632 (1947); J. F. Timmer, Medicamundi 19(2), 52-54 (1974); G. U. Rao, Appl. Radiol. 3(3), 45-49 (1974); R. Birch, Br. J. Radiol. 49, 951-955 (1976); W. W. Roeck, AAPM Symposium, 217-247 (1991)]. Off-focus radiation is frequently manifested on radiographs by the appearance of faint images of anatomical structures outside the collimated field of interest, i.e., soft tissues, ear lobes and hair, which we will refer to as "penumbral images." The observable small detail resolution within these penumbral images led to the assumption that minute sources of increased radiation intensity (secondary microfocal spots) must be present outside the area of the primary focal spot. The existence of these multiple secondary microfocal spots has been established and their locations within the area of the anode surface from which the general OFR originates was identified. The number, size, and distribution of the secondary focal spots vary over time and their magnitudes vary widely. The source of the well-focused electron beams creating the spots is attributed to the cold cathode emission principle. PMID- 1435600 TI - Performance characteristics of transmission imaging using a uniform sheet source with parallel-hole collimation. AB - Transmission imaging is receiving increasing attention in SPECT due to the need to compensate for nonuniform attenuation in cardiac-chest SPECT. The quality of a transmission image has an important effect on the measured attenuation distribution. To improve image quality, knowledge of the performance characteristics of a transmission imaging system is essential. The characteristics, spatial resolution, detection efficiency, photon flux, and exposure to the object, of a transmission imaging system consisting of a gamma camera and a uniform sheet source have been studied. The results demonstrate that spatial resolution of a transmission imaging system can be improved by use of a high-resolution source collimator at the price of a moderate decrease in detection efficiency, in comparison to the uncollimated case. Also, the source collimator significantly reduces the photon flux and exposure to the object. This investigation suggests that a high-resolution collimator be used with an intense sheet source to improve spatial resolution and reduce statistical noise with low exposure to the patient. This research further suggests that the amount of source activity is determined by the requirement of image quality, detection geometry, and allowed absorbed dose to the patient. PMID- 1435601 TI - Comparisons of sectioned micro-TLD dose measurements with predicted dose from 131I-labeled antibody. AB - The dose distribution from radioimmunotherapy is very heterogeneous because of variability in antigen expression, antibody penetration, and tumor architecture. Many models of dose distribution have been constructed but it has been very difficult to confirm these predictions with actual measured doses. The purpose of this study was to determine what degree of resolution could be obtained using mini-thermoluminescent dosimeter(s) (TLD) in a micrometastasis model. TLDs were inserted into 1-mm-diam multicell tumor spheroids that had been treated with 131I labeled antibody. The spheroids were then sectioned at 30-microns intervals and the TLD sections (measuring 0.14 x 0.1 x 0.03 mm) were removed and read. Calibration of the TLDs was done with whole TLDs using external beam radiation and an 131I-containing gel, and with TLD sections using external beam radiation. Predicted doses were determined by measuring the activity in individual spheroids and the time the TLDs were in the spheroids and incorporating these numbers into a model that assumed either surface binding of 131I or some degree of penetration. There was a correlation between the measured TLD dose and the predicted absorbed dose when comparing the low- to high-dose regions. However, there was considerable variation within any particular dose range, probably due to heterogeneity in TLD grain size.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435602 TI - A technical analysis of an intraoperative radiation detection probe. AB - A technical evaluation was made of a commercial intraoperative radiation probe. This device utilizes a CsI (T1) scintillation detector and light pipe arrangement to count gamma radiation in vivo. After determining the optimal window and threshold setting, additional evaluations included linearity, distance response function, detector dead time, counter reproducibility, detector sensitivity, angular resolution, and energy resolution. Detector dead time (21.2 microseconds) was found to be characteristic of a nonparalysable system. Activity response for each radionuclide was linear (R = 0.99) both with and without collimation. Energy resolution, 25% at 210 keV, was not sufficient to separate the two photons (172 and 247 keV) emitted by 111In. Detector sensitivity was 1136 and 626 counts per s per microcurie of 111In and 99mTc, respectively. The mean effective distance from the face of the uncollimated probe to the crystal was determined to be 2.03 cm in air. PMID- 1435603 TI - Acronyms in bone densitometry. PMID- 1435604 TI - The advantages of absorbed-dose calibration factors. AB - A formalism for clinical external beam dosimetry based on use of ion chamber absorbed-dose calibration factors is outlined in the context and notation of the AAPM TG-21 protocol. It is shown that basing clinical dosimetry on absorbed-dose calibration factors ND leads to considerable simplification and reduced uncertainty in dose measurement. In keeping with a protocol which is used in Germany, a quantity kQ is defined which relates an absorbed-dose calibration factor in a beam of quality Q0 to that in a beam of quality Q. For 38 cylindrical ion chambers, two sets of values are presented for ND/NX and Ngas/ND and for kQ for photon beams with beam quality specified by the TPR20(10) ratio. One set is based on TG-21's protocol to allow the new formalism to be used while maintaining equivalence to the TG-21 protocol. To demonstrate the magnitude of the overall error in the TG-21 protocol, the other set uses corrected versions of the TG-21 equations and the more consistent physical data of the IAEA Code of Practice. Comparisons are made to procedures based on air-kerma or exposure calibration factors and it is shown that accuracy and simplicity are gained by avoiding the determination of Ngas from NX. It is also shown that the kQ approach simplifies the use of plastic phantoms in photon beams since kQ values change by less than 0.6% compared to those in water although an overall correction factor of 0.973 is needed to go from absorbed dose in water calibration factors to those in PMMA or polystyrene. Values of kQ calculated using the IAEA Code of Practice are presented but are shown to be anomalous because of the way the effective point of measurement changes for 60Co beams. In photon beams the major difference between the IAEA Code of Practice and the corrected AAPM TG-21 protocol is shown to be the Prepl correction factor. Calculated kQ curves and three parameter equations for them are presented for each wall material and are shown to represent accurately the kQ curve for all ion chambers in this study with a wall of that specified material and a thickness less than 0.25 g/cm2. Values of kQ can be measured using the primary standards for absorbed dose in photon beams. PMID- 1435605 TI - Electron dose calculation using multiple-scattering theory: evaluation of a new model for inhomogeneities. AB - In this article, the fifth in a series on the calculation of electron dose using multiple-scattering theory, the predictions of a new model for dealing with localized inhomogeneities will be examined (Med. Phys. 18, 123-132, 1991). That model is in the form of a perturbation series, and for a thick half-slab configuration explicit formulas are worked out for the dose directly deposited by the primary electrons, for three reasonable cutoffs of the series. The predictions of this model with EGS4 Monte Carlo calculations for the half-slab configuration are compared, and they are found to be quite accurate in the region under the edge of the half-slab. On the other hand, the "Hogstrom algorithm," which is currently the most advanced method in routine clinical use, is found to give poor accuracy for this configuration. PMID- 1435606 TI - Clinical dosimetry for implementation of a multileaf collimator. AB - In order to initiate the use of a multileaf collimator (MLC) in the clinic, a set of technical procedures needs to be available sufficient to create MLC leaf settings and to deliver an accurate dose of radiation through the MLC-shaped field. Dosimetry data for clinical use of the MLC were measured. Dosimetric characteristics included central axis percent depth dose, output factors, and penumbra. In this paper, it has been concluded that a dose control monitor unit calculation procedure that has been applied to the use of conventional secondary field-shaping blocks can be applied to the multileaf collimator dosimetry. The multileaf collimator penumbra (20% to 80%) is only slightly wider (1-3 mm) than the penumbra of the conventional collimator jaws. Beam's-eye-view comparisons made between the isodose curves in fields shaped by conventional Cerrobend blocks and isodose curves in fields shaped by the multileaf collimator demonstrated that the 50% isodose line at 10-cm depth exhibited the discrete steps of the multileaf collimator leaves, but that the 90% and 10% isodose curves of the multileaf were close to those shaped by Cerrobend blocks. PMID- 1435607 TI - Skin dose measurements for head and neck radiotherapy. AB - The use of immobilization plastic masks in head and neck radiotherapy can partially eliminate skin benefits derived from the utilization of megavoltage photon beams. Filters and blocks between the patient and the accelerator can further increase the skin dose value. In this study, the increase in surface dose due to 2 and 3.2 mm of plastic material utilized for patient immobilization was measured. Then, the effect of blocking trays, wedges, and blocks on skin dose in typical conditions for head and neck irradiation was evaluated. The measurements were obtained with a NE2534 chamber (Markus type) on a perspex phantom for 6 MeV x-rays from an accelerator. PMID- 1435608 TI - Missing tissue compensators: evaluation and optimization of a commercial system. AB - A commercial system for producing retracted compensators has been adapted to suit local needs, and is evaluated here. It comprises a magnetic field surface digitizer and computer-driven milling machine. Improvements in dose distributions, resulting in standard deviations of the mean dose between 2% and 3%, have been achieved for treatment fields in wax phantoms simulating the head and neck regions. Optimization of compensator shape to allow for changes in the amount of scattered radiation has resulted in a further improvement in dose uniformity, particularly near the field borders; for these compensators the standard deviation was as low as 1.6%. The system using the basic algorithm has been in clinical use since July. PMID- 1435609 TI - Treatment planning for asymmetric jaws on a commercial TP system. AB - In this work, the accuracy of the asymmetric jaws planning feature in a commercial treatment planning (TP) system is assessed. In the latest version of this software, the off-axis beam quality variation is handled by a function g(d,r), which is derived from measured horizontal beam profiles at four different depths. The calculated and measured isodoses for a 6-MV linear accelerator with asymmetric jaws agree to +/- 0.5% along the central axis and to within 2 mm at the beam edge. Formulas for treatment time calculations using the output data reported by the computer program are described, as well as formulas for manual calculations based on pregenerated data tables. Doses calculated based on these formulas are compared to measurement and the accuracy is +/- 1% and +/- 2% for the computer and manual calculations, respectively. It is concluded that this version of the treatment planning system as well as the treatment time calculation formulas can be used adequately for asymmetric jaw computerized and manual treatment planning. PMID- 1435610 TI - Gadolinium neutron capture therapy for brain tumors: a computer study. AB - A Monte Carlo computer study of the total dose distribution from neutrons and prompt gamma emissions (but excluding the contribution from conversion and Auger electrons) for gadolinium neutron capture therapy of brain tumors has been carried out in order to test the theoretic feasibility of this modality using commercially available magnetic resonance contrast media. The three-dimensional dose distribution calculations were performed in a spherical head phantom with a spherical tumor at the center. Potentially achievable gadolinium concentrations of 150 micrograms/g of tissue in tumor and 3 micrograms/g in normal tissue were assumed with enrichment to 79.9% gadolinium-157, as supplied by Oak Ridge National Laboratory. Irradiation was assumed to be with a 2-keV monoenergetic cylindrical epithermal neutron beam having a radius of 4 cm. The three dimensional thermal neutron fluence resulting from the 2-keV beam propagation through the tissue was modeled. For a single neutron beam, the maximum dose is delivered within the tumor but the dose is very inhomogeneous across the tumor volume due to rapid decrease of thermal neutron fluence with depth. Two parallel opposed neutron beams deliver to the interface of normal and malignant tissue 70% 80% of the maximum dose received at the center of the tumor. To deliver an average tumor dose of 500 cGy in 10 min would require a 2-keV source neutrons number of 8.0 x 10(11) per s within the geometry of the beam. PMID- 1435611 TI - Neutron fluence and kerma spectra of a p(66)/Be(40) clinical source. AB - High-resolution neutron fluence spectra have been measured in the National Accelerator Centre's p(66)/Be(40) neutron therapy beam by the pulsed-beam time-of flight method. ICRU muscle kerma spectra have been derived from the fluence spectra. Spectral changes resulting from different irradiation conditions have been quantified in terms of the average neutron energy and the fractional low energy (< 16 MeV) contribution. The changes observed with different thicknesses of polyethylene filtration are consistent with changes in quality parameters determined in biological and microdosimetric experiments. The dosimetry parameters (KtissueA150) N and (Wgas) N calculated for the measured spectra agree with the values recommended in the neutron dosimetry protocol. The shapes of the present fluence spectra differ from previous measurements of p(> 40)/Be spectra. In particular, they differ significantly from the spectrum measured by recoil techniques in an identical neutron therapy unit at the Clatterbridge Hospital, UK. The reasons for the difference are not known. PMID- 1435612 TI - Evaluation of the buildup effect of an 192Ir high dose-rate brachytherapy source. AB - The buildup effect of the 192Ir radioactive source employed as a gamma emitter of the Selectron high dose-rate (HDR) afterloader was evaluated by studying the ratio of exposure in water to exposure in air as a function of distance. In 1968, Meisberger et al. [Radiology 90, 953-957 (1968)] calculated a third-order polynomial fit to a selected average between measured and calculated values. The objective of this investigation, however, is to evaluate the factor for the 192Ir source configuration used in the HDR system, which was different from the source design used by Meisberger et al. This paper presents the measured ratio using an ionization chamber and the calculated ratio using a Monte Carlo simulation code. The experimental and theoretical results show only minor disagreement with the data of Meisberger et al. However, the results show significant disagreement when they are compared to the model developed by van Kleffens and Star [Int. J. Radiat. Oncol. Biol. Phys. 5 557-563 (1979)], which may indicate the need to reevaluate the algorithm presently employed in HDR treatment planning system. The comparison with other published data will be discussed. PMID- 1435613 TI - Dose distributions produced by shielded applicators using 241Am for intracavitary irradiation of tumors in the vagina. AB - Dosimetric characteristics of shielded vaginal applicators containing encapsulated 241Am sources are investigated in this work. Encapsulated 241Am sources emit primarily 60-keV photons which are more effectively shielded by thin layers of high atomic number materials than the 662-keV photons from 137Cs sources. With 241Am, it is possible to achieve almost unidirectional irradiation of localized vaginal tumors. The drastic decrease in irradiation volume on the contralateral side (uninvolved with tumor) is observed to decrease dose by up to 20%, even in the forward direction (unshielded side toward the tumor) of the applicator. A possible explanation for the observed effects of shields in both the forward and backward directions is the reduction of scattered photon fluence due to absorption of photons in the lead shield via photoelectric effect. Current theoretical models do not include this perturbation effect caused by shields on brachytherapy applicators. PMID- 1435614 TI - Two-radiograph reconstruction using six geometrical solution sets and least squares method. AB - When two radiographic projections are available for reconstruction, it was found that six different combinations of equations could be used to obtain the geometrical solutions for the position of any point. No errors in the image coordinates read from the radiographs resulted in identical solutions for the six equations. Inaccuracies or errors present in the image coordinates generated differences among the six solutions. In this case, a least-squares method could be used to determine the optimum position. The utility of such a least-squares optimizing approach is presented in the context of a clinical example. PMID- 1435615 TI - Thermal and scatter effects on the radiation sensitivity of well chambers used for high dose rate Ir-192 calibrations. AB - High dose rate (HDR) iridium sources must be calibrated regularly because of the short half-life of Ir-192. High dose rate sources can now be calibrated using a new well-type chamber that allows easy, reproducible source calibrations. The chamber includes a styrofoam insulator that surrounds the source in the well. A study of the radiation sensitivity of the well chamber exposed to an HDR Ir-192 source at two different activities (300 and 230 GBq) revealed that the sensitivity of the chamber varies by as much as 1.1% as the chamber is moved toward a scattering surface. Second, with the styrofoam insulator removed, the air temperature within the ion collecting volume increased during exposure, causing a gradual decrease in chamber sensitivity of 0.15% in 30 min. This temperature increase was caused by heat transfer from radiation emitted by the Ir 192 source, and diminished as the source decayed. However, with the styrofoam insulator around the central aluminum tube in the well, the source cannot heat the collecting volume and thus thermal equilibrium between the ion collecting volume and its environment is maintained throughout an exposure. The radiation sensitivity of the commercial well chamber was found to be constant for exposure times of 30 min. PMID- 1435616 TI - Comments on: "Exact determination of the magnification factor for target lesions in a stereotactic frame". PMID- 1435617 TI - Green's function solution to the tissue bioheat equation. AB - A Green's function solution to the tissue bioheat equation including blood flow in cylindrical geometry is obtained. Numerical results for temperature variation in the bovine muscle are reported when the tissue is exposed to neodymium-yttrium aluminum garnett (Nd:YAG) lasers with Gaussian profile and a comparison with recent measurements is made. A strong dependence of the tissue temperature on the beam radius and pulse time is found. PMID- 1435618 TI - Thermocouples--the Arizona experience with in-house manufactured probes. AB - The performance of several different types of multisensor thermocouple probes have been tested to determine the feasibility of each type for use in the hyperthermia clinic. All of the probes tested were manufactured in-house, and a detailed description of the construction process will be presented. The overall performance of the probes in terms of robustness, calibration, conduction errors, and response time will be described. In particular, this study describes our experience with in-house manufactured thermocouples over the past several years. The results indicate that when strict quality assurance guidelines are followed, in-house manufactured thermocouples perform satisfactorily--thereby providing an alternative to purchasing probes and measurement systems from commercial vendors if the proper resources are available. PMID- 1435619 TI - Heat shock proteins in brain ischemia: role undefined as yet. PMID- 1435621 TI - Heat stroke during Hajj (Pilgrimage)--an update. PMID- 1435620 TI - Differential effects of metal ions on type A and type B monoamine oxidase activities in rat brain and liver mitochondria. AB - To investigate the hypothesis that neurotoxic metals can exert their toxicity through the direct inhibition of monoamine oxidases (MAOs), the effects of several neurotoxic metal ions on type A (MAO-A) and type B (MAO-B) monoamine oxidase activities in rat forebrain nonsynaptic mitochondria and rat liver mitochondria were studied. At pathophysiological levels (10-100 microM), Cu2+ and Cd2+ are good inhibitors of brain mitochondrial MAO-A and, to a lesser extent, liver mitochondrial MAO-A. The inhibition of MAO-B activities in brain and liver mitochondria by Cu2+ and Cd2+ is only detected at the higher end of the concentration range (i.e., 50-100 microM). At the pathophysiological level of 0.5 mM, Al3+ only inhibits brain mitochondrial MAO-A but at the higher level of 2.5 mM, it inhibits both forms of MAO in brain as well as liver mitochondria. Even at toxic levels (e.g., 5 mM), neither Mn2+ nor Li+ inhibits the activities of MAO-A and MAO-B in brain and liver mitochondria. Our results are consistent with the hypothesis that some neurotoxic metals can exert their toxicity through the direct inhibition of the isoforms of MAO. Our data also suggest that the selective inhibition of brain MAO-A by Cu2+ and Cd2+ may assume pathophysiological importance in the neurotoxicity of copper and cadmium. PMID- 1435622 TI - Postintubation tracheal damage. A four-year prospective study. AB - A 4-year prospective study was undertaken to estimate the incidence and identify the pathogenesis of cuff-induced major tracheal damage. All tracheal tubes were implantation tested and the cuffs were of the high-volume low-pressure type. The cuff pressure was continuously monitored and maintained below 3kPa. During the period of the study, 684 patients were intubated. Their average age was 33.6 years (range 14-296). The average intubation period was 9.3 days (range 1-256). At first, the damage was diagnosed clinically, radiologically and then confirmed by computed tomography. Three patients (0.4%) developed lesions that were not related to excessive (CP). In this study CP control seems to have eliminated a known major cause of intubation-associated tracheal injury. To date, there is no alternative to tracheal intubation. However the laryngeal mask seems ideal if invasion of the trachea is to be avoided altogether. PMID- 1435623 TI - The hemodynamic effects of propofol on the isolated rabbit heart. PMID- 1435624 TI - Flumazenil reversal of midazolam sedation for dental procedures. AB - The efficacy of flumazenil in the reversal of midazolam sedation was assessed in double-blind placebo controlled study. Thirty patients undergoing oral surgical procedures were included. Flumazenil administration was followed by immediate rise of the CNS functions scores to almost the baseline awake values. Compared to control group, patients were significantly more oriented and had better comprehension up to 15 minutes, more alert for 30 minutes and had better memory function up to 60 minutes. Peripheral oxygen saturation was significantly higher up to 15 minutes. Flumazenil allows better utilization and higher turn over rate where space and nursing resources are scarce. PMID- 1435625 TI - Anesthesia for neurosurgical emergencies. PMID- 1435626 TI - Pulmonary complications following cardiopulmonary bypass--a retrospective study. PMID- 1435627 TI - A reallocation of rights in industries with reproductive health hazards. AB - The U.S. Supreme Court ruling in United Automobile Workers versus Johnson Controls prohibits hiring policies that exclude fertile women from industries posing reproductive health risks to workers and fetuses. Many toxic substances that threaten the developing fetus also pose risks to adult male and female workers. Exclusionary employment policies are socially undesirable for the following reasons: they may lead to worse reproductive outcomes if the indirect effects of lower wages and less adequate health insurance in the alternative available jobs are considered. Second, the effect of such policies could damage the individual woman's overall well-being through its economic impact and her potential loss in autonomy. Third, occupational segregation into less hazardous but lower-paying jobs reinforces gender stereotypes that are restrictive to women. The Supreme Court ruling in the Johnson Controls case reaffirms the importance of the Civil Rights Act as both a shield against unfair treatment for individual women and a commitment to eradicate sexist attitudes and economic inequality throughout society. PMID- 1435628 TI - The introduction of cystic fibrosis carrier screening into clinical practice: policy considerations. AB - Routine prenatal testing for cystic fibrosis (CF) should be halted until the detection rate reaches 95 percent. Pilot studies are needed in order to evaluate the feasibility of meeting education, consent, and counseling requirements in order to facilitate informed reproductive decisions by clients and to minimize the potential for confusion, stigmatization, and discrimination. Primary care physicians may not be trained adequately to provide appropriate information, and prenatal visits may not be an ideal setting. The public's interest in carrier testing, prenatal testing, and pregnancy termination is uncertain because CF patients have an increasing median survival, variable disability, and normal intelligence. Even with a goal that limits testing for the purpose of informed reproductive decision making, the considerable cost of screening per case prevented must be considered before it becomes public policy. Until these issues have been clarified, the duty of primary care physicians is to inform patients of the test's availability and to refer interested patients to qualified genetic counselors rather than to provide the test themselves. PMID- 1435629 TI - A critical analysis of "moderation" advertising sponsored by the beer industry: are "responsible drinking" commercials done responsibly? AB - This analysis reveals several important advertising trends by the U.S. beer industry, whose purported aim has been to promote "moderation" in drinking. First, the brewers' prevailing interest in promoting consumption has resulted in the use of slogans and messages that ignore the fact that certain people should not drink at all, and, in certain circumstances, that no one should drink. Second, these ads do not consistently make clear that the acts of drinking and driving should remain entirely separate. Third, several aspects of these commercials undermine whatever moderation message they may provide, in particular the use of themes and images that are similar to the beer companies' regular brand promotions. In order to present an acceptable public health message, moderation advertising must not be dominated by glamorous presentations of alcohol consumption. In short, it must be done more responsibly. PMID- 1435630 TI - The use and cost of health services prior to death: a comparison of the Medicare only and the Medicare-Medicaid elderly populations. AB - Lack of data has limited research into the high cost and ethical dilemmas associated with care of the dying elderly. This study is based on a five-year, person-specific file of Medicare and Medicaid use and cost data for residents of Monroe County, New York, over the age of 65. It examines and compares utilization and expenditure patterns of the Medicare-only and the Medicare-Medicaid (dually eligible) decedents in 1988. Examination of reimbursement for nonacute services, not covered by Medicare, reveals that services for the "older old" may be less costly immediately prior to death than for younger decedents. However, when expenses in the year prior to the year of death are also counted, services for the dually eligible, older old decedents appear to be neither more nor less costly than for younger decedents. Distribution of expenses does, however, vary considerably with age. The younger decedents, aged 65 to 74, use 55 percent of their medical resources on hospital care, paid for by Medicare; the older old use 26 percent for hospital services and pay 67 percent for supportive care, reimbursed by Medicaid. The study suggests that medical intervention associated with dying is utilized more often and at a higher cost by younger decedents. PMID- 1435631 TI - The organized American medical profession's response to financial conflicts of interest: 1890-1992. AB - Recent issues of financial conflicts of interest for physicians are illuminated by the history of similar issues from 1890 to 1992 and the response of the organized medical profession to activities like payment of commissions, or "fee splitting," physical ownership of medical facilities, and dispensing of drugs. The medical profession tried to confront these and related conflicts early in the century, in some cases by adopting ethical codes, but was unable to enforce standards of conduct. Since the 1950s, substitutes for fee splitting emerged and were tolerated by the profession. Moreover, its stance became weaker as it abandoned its earlier clear ethical prohibitions and relied instead on subjective standards and, more recently, on disclosure to patients. The medical profession still favors voluntary codes of ethics, setting aspirational goals, promoting a patient-centered ethos, and relying on the good will of individual doctors- tactics for dealing with financial conflicts of interest that this review of recent history suggests are inadequate. Instead, public intervention is required to address these problems. PMID- 1435632 TI - Minnesota physicians and health care reform. After 'health right'. PMID- 1435633 TI - Will Minnesota's Health Care Reform Act assure fair access? PMID- 1435634 TI - Malpractice plaintiffs' attorneys. The mindset, the methods. PMID- 1435635 TI - What happens in a malpractice action? PMID- 1435636 TI - Health care reform and medical malpractice in Minnesota. PMID- 1435637 TI - Minnesota's Health Care Reform Act. Will the new law founder on antitrust fears? PMID- 1435638 TI - Searching for answers. Using computers to find the literature you need for patient care. AB - The medical journal literature is extensive and contains information that can help physicians care for patients. Minnesota physicians are able to tap into a variety of resources to help them locate relevant articles. Literature searches may be run by librarians in a local hospital library, a larger health sciences library, or via various professional associations. Physicians interested in conducting their own searches are able to use local systems or dial into national ones. Innovations in computers will allow easier and faster access to the medical literature in the future. PMID- 1435639 TI - Another abuse problem. PMID- 1435640 TI - CDC recommends routine HIV testing at some hospitals. PMID- 1435641 TI - In the wake of the Health Right Act. PMID- 1435642 TI - MMA's vision for 'health right'. Task force prepares strategy. PMID- 1435643 TI - The effects of childhood trauma upon adult recovery from injury and illness. AB - Many patients with chronic injury or illness suffer from childhood trauma syndrome. As a result, they do not take proper care of themselves and are at risk of developing long-term disabilities. Physicians who understand the dynamics of CTS can help these patients regain control over their own bodies and health. By building therapeutic relationships with these patients, physicians can restore trust and help them lead happier, healthier lives. PMID- 1435644 TI - Emergency medicine. The rural challenge. AB - Overcrowding, stress-related job burnout for emergency room physicians and other personnel, violence spilling over into the hospital with the surge in gang activity--it's the stuff of movies and, increasingly, real life in urban emergency departments, even in Minnesota. The trials and tribulations of providing emergency medical care in our metropolitan areas are well documented, both in professional journals and the conventional media. It's dramatic--lives hang in the balance--and it's important to everyone, since those who will one day require emergency medical care must entrust their well-being to this system. But it's only part of the story. PMID- 1435645 TI - A Minnesota perspective on childhood lead poisoning. PMID- 1435646 TI - Lead levels among pregnant women in Hennepin County. AB - The purpose of this study was to determine the blood lead levels (Pb-B) of urban pregnant women with low incomes and/or living in areas with heavily traveled roads, dilapidated housing, and industrial plants. We measured blood lead in 1,055 pregnant Minneapolis-area women at entry to prenatal care and in one-third of the sample during the second half of pregnancy. The mean Pb-B level of the first sample (n = 1,055) was 1.83 +/- 1.83 micrograms/dL; of the second sample (n = 375), 1.99 +/- 1.92 micrograms/dL. Only one woman had a Pb-B level greater than 12.0 micrograms/dL, which was the result of occupational exposure. The low lead levels found in this study indicate that it is not necessary to routinely screen pregnant women for elevated Pb-B levels in our geographic area. Rather, women should be screened via an environmental questionnaire to ascertain the risk of lead exposure. PMID- 1435647 TI - MnCare will likely face legal hurdles. PMID- 1435648 TI - The Minnesota Limited Liability Company Act. Physician groups likely to find new law beneficial. PMID- 1435649 TI - The three A's. PMID- 1435650 TI - FDA to collect fees from drug companies. PMID- 1435651 TI - Drug, alcohol use down among Minnesota students. PMID- 1435652 TI - U.S. children's health declining. PMID- 1435653 TI - Childhood lead poisoning. How serious a threat? PMID- 1435654 TI - Rural EMS: making it work in Minnesota. PMID- 1435655 TI - Mountain sickness. AB - This article outlines the fundamental physiology and pathology of high altitude. It covers the latest findings from the unique experiment Operation Everest II in which eight persons were gradually decompressed to the "summit" of Mt. Everest and extensive physiologic studies done. The article contains an examination of the various high altitude pathologies, including acute mountain sickness, high altitude pulmonary edema, high altitude cerebral edema, and high altitude retinal hemorrhage. Information on prevention and current approaches to treatment conclude the article. PMID- 1435656 TI - Neurologic injury from undersea diving. AB - Underwater diving may cause several unique neurologic injuries because of exposure to rapid changes in pressure and volume. DCS, which results from extended deep dives and too rapid ascent, is a systemic disease that frequently causes spinal cord injury but may involve other organs as well. AGE results from pulmonary overpressure on ascent, with extravasation of air into the arterial system, and causes stroke-like brain injury. Both conditions are of sudden onset, progress rapidly, and require urgent attention. Definitive treatment includes administration of oxygen and recompression in a chamber. Permanent neurologic injury may result. PMID- 1435657 TI - Lightning and electrical injuries. AB - Lightning and electrical injuries are similar in that both produce immediate tissue injury from burn and trauma induced by fall and both can arrest the heart and respiratory center. Immediate support of circulation and respiration is life saving. Subsequently the nervous system may show signs of injury, and seizures, cerebral edema, and muscle and nerve lesions should be handled as the indications arise. Prevention of the injury is more effective than any postinjury treatment. Outdoors hikers and campers must take shelter to minimize their exposure; indoors properly installed equipment and attention to the relation of the equipment user to the electrical ground are the key elements in avoiding electrocution. PMID- 1435658 TI - Neurologist as expert witness. AB - Prevailing liberal rules of evidence permit qualified medical and scientific experts to offer opinions designed to help courts decide issues to which their expertise relates. The opinions can be based on direct examinations, review of data assembled by others and data or inferences of a type relied on by other experts in the field. Application of these rules is illustrated through analysis of expert testimony in litigation involving a neurologic syndrome allegedly caused by an immunization and in a case involving controversy over the extent and outcome of major brain injury. Concerns about misuse of expert medical and scientific testimony in litigation are addressed. The article closes with a consideration of approaches designed to improve the reliability of expert testimony. PMID- 1435659 TI - The postconcussion syndrome and the sequelae of mild head injury. AB - The postconcussion syndrome refers to a large number of symptoms and signs that may occur alone or in combination following usually mild head injury. The most common complaints are headaches, dizziness, fatigue, irritability, anxiety, insomnia, loss of consciousness and memory, and noise sensitivity. Mild head injury is a major public health concern because the annual incidence is about 150 per 100,000 population, accounting for 75% or more of all head injuries. The postconcussion syndrome has been recognized for at least the last few hundred years and has been the subject of intense controversy for more than 100 years. The Hollywood head injury myth has been an important contributor to persisting skepticism and might be countered by educational efforts and counter-examples from boxing. The organicity of the postconcussion syndrome has now become well documented. Abnormalities following mild head injury have been reported in neuropathologic, neurophysiologic, neuroimaging, and neuropsychologic studies. There are multiple sequelae of mild head injury, including headaches of multiple types, cranial nerve symptoms and signs, psychologic and somatic complaints, and cognitive impairment. Rare sequelae include hematomas, seizures, transient global amnesia, tremor, and dystonia. Neuroimaging and physiologic and psychologic testing should be used judiciously based on the problems of the particular patient rather than in a cookbook fashion. Prognostic studies clearly substantiate the existence of a postconcussion syndrome. Manifestations of the postconcussion syndrome are common, with resolution in most patients by 3 to 6 months after the injury. Persistent symptoms and cognitive deficits are present in a distinct minority of patients for additional months or years. Risk factors for persisting sequelae include age over 40 years; lower educational, intellectual, and socioeconomic level; female gender; alcohol abuse; prior head injury; and multiple trauma. Although a small minority are malingerers, frauds, or have compensation neurosis, most patients have genuine complaints. Contrary to a popular perception, most patients with litigation or compensation claims are not cured by a verdict. Treatment is individualized depending on the specific complaints of the patient. Although a variety of medication and psychologic treatments are currently available, ongoing basic and clinical research of all aspects of mild head injury are crucial to provide more efficacious treatment in the future. PMID- 1435660 TI - Posttraumatic cranial neuropathies. AB - Injury to cranial nerves is a common sequela of blunt head trauma. The olfactory, facial, and audiovestibular nerves are damaged most often, followed by the optic and ocular motor nerves. The trigeminal and lower cranial nerves are rarely involved. Chances of recovery are greatest for the facial nerve, intermediate for the ocular motor nerves, and least likely for the olfactory, optic, and audiovestibular nerves. Treatment is usually symptomatic, although steroids or surgical decompression of the optic and facial nerves can lead to dramatic results in selected patients. PMID- 1435661 TI - Posttraumatic epilepsy. AB - The risk for development of posttraumatic epilepsy is generally related to the severity of injury or the brain trauma dose. This article discusses mechanisms and biomechanical effects of brain injury. Genetic factors, prevention and prophylaxis, and the use of antiepileptic drugs are discussed also. PMID- 1435662 TI - Cognitive impairment following closed head injury. AB - Cognitive impairments are usually the most disabling sequelae of CHI. The earliest stage of recovery from moderate to severe closed head injury is a period of PTA that typically includes memory loss for events preceding and surrounding the injury and memory loss for events occurring since the injury. Following resolution of PTA, deficits may be present in a number of cognitive domains. Memory and attention/information processing speed and efficiency are typically the cognitive domains most severely affected by head injury. Intellectual, language, and perceptual skills tend to be relatively preserved. Neurologic variables such as pupillary reactivity and worst GCS score are prognostic of cognitive impairment at 1 to 2 years postinjury. Following mild head injury, impairments of memory and information processing may be apparent within the first week of recovery. These deficits usually resolve in 1 to 3 months, although chronic complaints persist in a minority of individuals. The long-term cognitive effects of CHI are typically more severe for younger children than older children. Neuropsychologic assessment provides an objective way to measure the presence and severity of cognitive impairment. PMID- 1435663 TI - Psychiatric aspects of the neurology of trauma. AB - This article discusses posttraumatic stress disorders, their relationship to conversion and dissociation responses, and the role of neurologic examination in diagnosis. The concentration camp syndrome (CSS) and its organic and psychological components, the emotional impact of physical illness, and psychiatric syndromes related to brain lesions are presented also. PMID- 1435664 TI - Trauma and movement disorders. AB - Movement disorders have been linked to trauma; however, these cases are uncommon and best substantiated if the movement disorder occurs in close temporal association with the trauma, occurs in context of other clinical signs of neurologic damage, and if evidence of CNS lesions on neuroimaging scans is evident. The pathophysiology of movement disorders relates to basal ganglia dysfunction, and traumatic lesions of peripheral nervous system structures or cortical regions could theoretically alter basal ganglia function indirectly and influence movement disorders. Parkinson's disease, the prototype of movement disorders, does not appear to be caused by trauma. PMID- 1435665 TI - Reflex sympathetic dystrophy and causalgia. AB - Converging lines of research suggest that RSD is a form of reflex neurogenic inflammation. Early the sympathetic nervous system appears to have an initiating and sustaining role. In later states of the illness, structural changes at the DH level seem to correlate with centralization of the process. Neuropeptides and EAAs released from thin or unmyelinated nociceptive afferents may produce both the inflammation and the suspected central sensitization of DH neurons seen in later stages of the disease. Effective treatment will follow a clearer understanding of the physiology of each stage of the disease. PMID- 1435666 TI - Some observations on whiplash injuries. AB - Motor vehicle accidents with a whiplash mechanism of injury are one of the most common causes of neck injuries, with an incidence of perhaps 1 million per year in the United States. Proper adjustment of head restraints can reduce the incidence of neck pain in rear-end collisions by 24%. Persistent neck pain is more common in women by a ratio of 70:30. Whiplash injuries usually result in neck pain owing to myofascial trauma, which has been documented in both animal and human studies. Headaches, reported in 82% of patients acutely, are usually of the muscle contraction type, often associated with greater occipital neuralgia and less often temporomandibular joint syndrome. Occasionally migraine headaches can be precipitated. Dizziness often occurs and can result from vestibular, central, and cervical injury. More than one third of patients acutely complain of paresthesias, which frequently are caused by trigger points and thoracic outlet syndrome and less commonly by cervical radiculopathy. Some studies have indicated that a postconcussion syndrome can develop from a whiplash injury. Interscapular and low back pain are other frequent complaints. Although most patients recover within 3 months after the accident, persistent neck pain and headaches after 2 years are reported by more than 30% and 10% of patients. Risk factors for a less favorable recovery include older age, the presence of interscapular or upper back pain, occipital headache, multiple symptoms or paresthesias at presentation, reduced range of movement of the cervical spine, the presence of an objective neurologic deficit, preexisting degenerative osteoarthritic changes; and the upper middle occupational category. There is only a minimal association of a poor prognosis with the speed or severity of the collision and the extent of vehicle damage. Whiplash injuries result in long-term disability with upward of 6% of patients not returning to work after 1 year. Although litigation is very common and always raises questions of secondary gain in patients with persistent symptoms, most patients are not cured by a verdict. Acute treatment of neck pain consists of ice for 24 hours followed by heat applications, pain pills, NSAIDs, and muscle relaxants. Trigger point injections can be beneficial in both the acute and the persistent phases. Use of cervical collars should probably be kept to a minimum during the first 2 to 3 weeks after the injury and then avoided. Early passive mobilization and range of motion exercises may accelerate recovery. Physical therapy and transcutaneous nerve stimulators may be helpful in reducing pain and improving movement.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1435667 TI - Neurology of microgravity and space travel. AB - Exposure to microgravity and space travel produce several neurologic changes, including SAS, ataxia, postural disturbances, perceptual illusions, neuromuscular weakness, and fatigue. Inflight SAS, perceptual illusions, and ocular changes are of more importance. After landing, however, ataxia, perceptual illusions, neuromuscular weakness, and fatigue play greater roles in astronaut health and readaptation to a terrestrial environment. Cardiovascular adjustments to microgravity, bone demineralization, and possible decompression sickness and excessive radiation exposure contribute further to medical problems of astronauts in space. A better understanding of the mechanisms by which microgravity adversely affects the nervous system and more effective treatments will provide healthier, happier, and longer stays in space on the space station Freedom and during the mission to Mars. PMID- 1435668 TI - The management of acute diarrhea in children: oral rehydration, maintenance, and nutritional therapy. Centers for Disease Control and Prevention. AB - Worldwide, diarrhea remains one of the most common illnesses among children. In the United States, children < 5 years of age experience > 20 million episodes of diarrhea each year, leading to several million doctor visits, 200,000 hospitalizations, and approximately 400 deaths. Much of this morbidity is due to the dehydration associated with acute watery diarrhea. Consequently, the proper management of children with acute diarrhea is important for all practitioners as well as for parents of small children. The development of oral therapy for the rehydration and maintenance of children with dehydrating diarrhea has become the worldwide mainstay of national diarrheal control programs. More recently, proper nutrition for children with diarrhea is viewed as an important adjunct to therapy, whereas antibiotics and other drugs play only a limited role. Intravenous therapy remains essential for diarrheal episodes associated with severe dehydration. This document reviews the proper management of diarrhea among children. Particular attention is given to the use of oral therapy for rehydration and maintenance therapy for the dehydrated child and nutritional management. In the United States, the improved management of children with diarrhea could lead to a noticeable decrease in the number of children who are hospitalized or die as a result of diarrheal illness. This report contains recommendations prepared by the Centers for Disease Control and Prevention (CDC), with input from a panel of pediatric and diarrheal management experts, which are consistent with recommendations endorsed by the American Academy of Pediatrics. PMID- 1435669 TI - Incidence of treatment for end-stage renal disease attributed to diabetes mellitus--United States, 1980-1989. AB - End-stage renal disease (ESRD) is defined as renal insufficiency requiring dialysis or kidney transplantation for survival. In the United States, diabetes mellitus is the major cause of ESRD. This report summarizes trends during the 1980s in the incidence of treatment for ESRD attributable to diabetes mellitus (ESRD-DM). PMID- 1435670 TI - Hospitalizations for diabetic ketoacidosis--Washington State, 1987-1989. AB - Diabetic ketoacidosis (DKA) is an acute metabolic complication of diabetes mellitus that can be life threatening. Although DKA is often preventable, approximately 84,000 DKA-associated hospitalizations and 1800 DKA-associated deaths occurred in the United States during 1988. The Washington Department of Health (WDH) monitors DKA-associated hospitalizations to assist its chronic disease programs in preventing DKA-associated hospitalizations and deaths. This report summarizes surveillance of DKA hospitalizations among Washington state residents from 1987 through 1989. PMID- 1435671 TI - Incidence of treatment for end-stage renal disease attributed to diabetes mellitus, by race/ethnicity--Colorado, 1982-1989. AB - Diabetes mellitus (DM) is the principal known cause of end-stage renal disease (ESRD) (i.e., renal insufficiency requiring kidney dialysis or transplantation for survival) and accounts for one third of all incident cases of treated ESRD in the United States. Rates for initiating diabetes-related ESRD (ESRD-DM) treatment have been characterized for blacks and whites but have not been well characterized for Hispanics. To describe ESRD-DM treatment by race/ethnicity in Colorado for improved program planning for intervention services, the Colorado Diabetes Surveillance Project of the Colorado Department of Health investigated differences in the rates of initiating ESRD-DM treatment for non-Hispanic white, Hispanic, and black Colorado residents with diabetes. This report describes trends in the incidence of ESRD-DM treatment by race/ethnicity among persons with diabetes in Colorado from 1982 through 1989. PMID- 1435672 TI - The Great American Smokeout--November 19, 1992. PMID- 1435673 TI - Cigarette smoking among Southeast Asian immigrants--Washington state, 1989. AB - Since 1975, approximately one million Southeast Asians have immigrated to the United States. In general, the efforts of local public health agencies to meet the needs of these immigrants have focused on identifying and treating acute and chronic diseases rather than identifying and modifying health-risk behaviors (e.g., smoking) among these immigrants. However, efforts to determine the prevalence of smoking suggest that smoking rates are high, especially among men of Southeast Asian origin. During 1989, to characterize cigarette smoking among Southeast Asian immigrants, the Seattle-King County (Washington) Health Department surveyed newly arriving Southeast Asian immigrants who intended to reside in the county regarding their health problems and health-risk behaviors. This report summarizes survey findings regarding their smoking habits. PMID- 1435674 TI - Cigarette smoking among American Indians and Alaskan Natives--Behavioral Risk Factor Surveillance System, 1987-1991. AB - Cardiovascular disease and cancer are two of the leading causes of premature death among American Indians and Alaskan Natives. Although cigarette smoking contributes to these diseases, cigarette smoking behaviors among American Indians and Alaskan Natives have not been well characterized nationally. To better assess the impact of smoking on these populations, CDC analyzed data obtained from the Behavioral Risk Factor Surveillance System (BRFSS) during 1987-1991. This report summarizes the findings from this study. PMID- 1435675 TI - World AIDS day--December 1, 1992. PMID- 1435676 TI - HIV instruction and selected HIV-risk behaviors among high school students- United States, 1989-1991. AB - Efforts to prevent human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) in the United States must be targeted toward persons of all age groups at risk, including adolescents. Many high school students have reported engaging in behaviors that increase their risk for HIV infection (1,2). During April and May of 1989, 1990, and 1991, CDC conducted three national school-based surveys among high school students that addressed, in part, HIV-risk behavior and school-based instruction. This report summarizes findings from these surveys. PMID- 1435677 TI - AIDS Community Demonstration Projects: implementation of volunteer networks for HIV-prevention programs--selected sites, 1991-1992. AB - States and cities have effectively used community-level intervention projects to reduce cigarette smoking and other risk behaviors associated with chronic disease (1-3); similar strategies have been introduced to prevent human immunodeficiency virus (HIV) infection in men who have sex with men and who identify themselves as homosexual or bisexual (4,5). Many of these projects used community volunteers to deliver interventions (2,4,5). An important concern for community-level intervention projects that rely on volunteers is the need to address the recruitment and retention of these volunteers. CDC AIDS Community Demonstration Projects have developed and maintained volunteer networks among hard-to-reach populations for HIV prevention. This report summarizes methods used by demonstration projects in five cities to develop and maintain volunteer networks during 1991-1992. PMID- 1435678 TI - HIV infection and AIDS--Georgia, 1991. AB - Public health surveillance efforts for acquired immunodeficiency syndrome (AIDS) in the United States have documented an increasing proportion of cases among persons who reside outside the largest metropolitan areas (1,2). These findings, coupled with results of human immunodeficiency virus (HIV) prevalence studies, have led to the development of HIV-related prevention and treatment services in smaller cities and rural areas. This report presents results of HIV-infection and AIDS surveillance in Georgia (1990 population: 6.5 million) for 1991 and compares these findings for urban and rural areas. PMID- 1435679 TI - Advisory Committee on Immunization Practices update: report of PedvaxHIB lots with questionable immunogenicity. PMID- 1435680 TI - Trends in years of potential life lost before age 65 among whites and blacks- United States, 1979-1989. AB - The reduction of preventable deaths among minority populations in the United States is a national health objective for the year 2000 (1). One measure used to assess progress toward this objective is years of potential life lost before age 65 (YPLL-65), which measures the impact of deaths occurring in years preceding 65 years of age and emphasizes the effects of deaths among younger persons (2). This report compares trends in YPLL-65 among U.S. whites and blacks from 1979 through 1989. PMID- 1435681 TI - National drunk and drugged driving prevention month--December 1992. PMID- 1435682 TI - Factors potentially associated with reductions in alcohol-related traffic fatalities--United States, 1990 and 1991. AB - Traffic crashes are the single greatest cause of death among persons aged 5-32 years in the United States (1); almost half of all traffic fatalities are alcohol related (1,2). An estimated 40% of persons in the United States may be involved in an alcohol-related traffic crash sometime during their lives (1). In 1991, the number of alcohol-related traffic fatalities (ARTFs) declined almost 10% when compared with 1990 (3), and the total number of deaths during 1991 (19,900) is the lowest since more complete alcohol-related fatal crash data became available in 1982. This report summarizes data from the National Highway Traffic Safety Administration's (NHTSA) Fatal Accident Reporting System on trends in ARTFs in the United States from 1982 through 1991 and presents information regarding several factors potentially related to the decline in fatalities during 1991. PMID- 1435683 TI - Heterosexual transmission of HIV--Puerto Rico, 1981-1991. AB - Puerto Rico has the second highest overall rate of acquired immunodeficiency syndrome (AIDS) cases among states and territories of the United States and the second highest rate of cases among women (1,2). Although heterosexual transmission of human immunodeficiency virus (HIV) among persons reported with AIDS has increased throughout the United States--accounting for 8% of all U.S. AIDS cases diagnosed in 1991 (2,3)--the proportion of cases attributed to heterosexual transmission is highest in Puerto Rico (18%). This report summarizes data collected through the Puerto Rico AIDS Surveillance Program to characterize AIDS cases associated with heterosexual transmission during 1981-1991. PMID- 1435684 TI - Cardiovascular disease control efforts among primary-care physicians--Missouri, 1990. AB - Nearly half (43%) of all deaths in the United States each year are related to cardiovascular diseases (CVD), including coronary heart disease and cerebrovascular disease (1). CVD is linked to certain risk factors and behaviors, including high blood pressure, elevated total serum cholesterol, cigarette smoking, and physical inactivity (2). Because approximately 70% of the population has at least one contact with a physician each year (3), primary-care physicians are central to health promotion and disease-prevention efforts and early detection of CVD. In May and August 1990, the Missouri Department of Health (MDH) conducted a survey of practicing Missouri physicians to characterize their efforts to identify and control CVD risk factors among their patients. PMID- 1435685 TI - Quarterly table reporting alcohol involvement in fatal motor-vehicle crashes. PMID- 1435686 TI - Abortion surveillance--United States, 1989. AB - Since 1980, the number of legal induced abortions reported to CDC has remained stable, varying each year by < 5%. In 1989, 1,396,658 abortions were reported--a 1.9% increase from 1988. The abortion ratio for 1989 was 346 legal induced abortions/1,000 live births, and the abortion rate was 24/1,000 women ages 15-44 years. The abortion ratio was highest for black women and women of other minority racial groups and for women < 15 years of age. Overall, women undergoing abortions tended to be young, white, and unmarried; to have had no previous live births; and to be having the procedure for the first time. Approximately half of all abortions were performed before the eighth week of gestation, and 87% were before the thirteenth week of gestation. Younger women tended to obtain abortions later in pregnancy than older women. This report also includes newly reported abortion-related deaths for 1986 and 1987, as well as an update on abortion related deaths for the period 1978-1985. Ten deaths in 1986 and six deaths in 1987 were associated with legal induced abortion. The case-fatality rate in 1986 was 0.8 abortion-related deaths/100,000 legal induced abortions and 0.4/100,000 in 1987. PMID- 1435687 TI - Influenza surveillance--United States, 1991-92. AB - During the 1991-92 influenza season, sustained regional influenza activity began to be reported by state and territorial epidemiologists in the United States in mid-October 1991. Sustained reporting of widespread influenza activity began in early November 1991, 5-10 weeks earlier than in any of the previous nine influenza seasons. Influenza caused substantial morbidity among school-age children and excess mortality among the elderly. Regional outbreaks of influenza ended 2-6 weeks earlier than in the previous nine influenza seasons, based on the last sustained state and territorial epidemiologists' reports. Nationally, > 99% of isolates were influenza A. Influenza A(H3N2) predominated in all regions of the country, but isolation of influenza A(H1N1) increased proportionally as the season progressed. Isolation of influenza B (< 1% of total isolates) clustered after February. The majority of isolates characterized were antigenically similar to components in the 1991-92 influenza vaccine. However, an influenza A(H1N1) strain that had undergone antigenic drift was detected in many regions of the country; this strain will be included in the 1992-93 influenza vaccine. PMID- 1435688 TI - [Innovative elastomeric bio-adhesive (pup-201) synthesized by urethane prepolymer]. AB - Properties of PUP-201 for the application to vital organs were estimated. Basic properties of PUP-201 were compared with two kinds of commercial fibrin and synthetic adhesives. Its initial and wet adhesive strength was 40 and 150 times stronger than those of fibrin adhesives respectively. Its curing time was 50 seconds, and elongating rate was 150% nearly as same as that of the intestine. This adhesive had not antimicrobial activities. The strength of adhesive bonded pig skin in shear by tension loading by way of JIS K6850 recorded 2.0-2.7kg/cm2 five minutes after, and 2.0-2.8kg/cm2 after 24 hours. The results of the same test in small intestine defined 0.4-1.0kg/cm2 in sero-sero attachment. There was no toxicity on the pig skin. Practical examinations for application to hemostasis on the section of dog liver and sealing of the lung section were performed successfully. PUP-201 was demonstrated excellently useful material for the adhesive, hemostasis and sealant of vital tissue. PMID- 1435689 TI - [In vivo effect of interleukin-2 (IL-2) on immunopotentiation in irradiated mice]. AB - This study's purpose was to evaluate the effect of IL-2 on the recovery from immunosuppressive state in vivo. Young adult mice (ddY) were rendered immunodeficient by whole body irradiation (300 rad). IL-2 (20000 u/head/day) was administered intraperitoneally for 5 days after irradiation. In the experiment (I) immunological parameters were investigated. In the IL-2-treated mice peripheral lymphocytes and neutrophils were increased, but there was no change in the T and B lymphocyte ratio. The proliferative responses of spleen cells to mitogens were improved in the IL-2-treated mice. A significant expansion of macrophages in the intraperitoneal cavity was demonstrated. In the experiment (II) irradiated mice were given peritonitis by 1 puncture with a 23 gauge needle through their ligated cecum. This peritonitis model was followed for 2 weeks after ligation and puncture of the cecum. In the mice with IL-2 pretreatment and antibiotic therapy, the survival rate was significantly improved, compared with mice that only received antibiotic therapy. Administration of carrageenan and anti-T cell monoclonal antibodies significantly decreased the survival rate. These results suggested macrophages as well as functional T cells were necessary to decrease the mortality rate. In conclusion, IL-2 may have a remarkably protective effect against infection in immunodeficient state. PMID- 1435690 TI - [Motility and mucosal hemodynamics of the lower esophagus after transabdominal esophageal transection for esophageal varices]. AB - Lower esophageal motility and mucosal hemodynamics were investigated in 20 patients who underwent transabdominal esophageal transection for esophageal varices (ET), to evaluate their association with reflux esophagitis and variceal recurrence. In the manometric study with microtransducer catheter, maximum swallowing pressure in the lower esophagus of the patients was significantly lower than that of the healthy controls (20 cases) (26.1 +/- 20.5mmHg vs. 80.0 +/ 10.0mmHg: p < 0.01), while high pressure zone pressure did not differ between the two groups. In comparison between patients with and without esophagitis (E(+) and E(-)), maximum swallowing pressure of E(+) was statistically lower than that of E(-) (12.4 +/- 18.7mmHg vs. 31.0 +/- 19.1mmHg: p < 0.05). In the hemodynamic study by reflectance spectrophotometry, the index of esophageal mucosal blood volume (IHb) and the index of oxygen saturation of hemoglobin (ISo2) of E(+) and E(-) were no different from those in the patients with non-operated esophageal varices (10 cases). Although there was no correlation between the recurrence of RC-sign and mucosal microcirculation, the patients with larger varices tended to have a higher IHb and a patients with F1-varices had significantly lower ISo2 than the patients without varices. This study indicated that the poor clearance ability after ET may lead to reflux esophagitis and the patients with variceal recurrence had the congested mucosal microcirculation, compared to those without variceal recurrence. PMID- 1435691 TI - [Histopathological features of the lymph node metastases in patients with thoracic esophageal cancer]. AB - Histopathological features of the lymph node involvement were studied in 104 patients with thoracic esophageal cancer who underwent subtotal esophagectomy combined with extended radical lymph adenectomy in cervicothoracoabdominal region. Metastatic involvement was found in a total number of 503 lymph nodes from 73 patients by histologic examination. The mean of long and short diameter was found to be less than 5mm in 125 (24.9%) of these 503 nodes. The involved area on the section was less than one third in 149 nodes (29.6%), and was significantly smaller in mediastinal lymph nodes than those in cervical or abdominal ones. Sixty-seven (13.3%) of 503 nodes were partially invaded by micrometastasis of 1mm or less in diameter. Micrometastasis also more frequently occurred in mediastinal nodes with a statistically significant difference. Extranodal proliferation (ENP) of cancer cells was found in 106 nodes (21.1%), and extranodal lymphatic and/or blood vessel invasion (ENly, v) was also recognized in 60 nodes (11.9%). Micrometastasis and ENP with or without ENly, v were found in 24 (32.9%) and 29 (39.7%) of 73 patients with positive lymph node metastasis, respectively. Postoperative survival rate in patients with micrometastasis and/or ENP with or without ENly, v was inferior to that in patients with neither of them. PMID- 1435692 TI - [Decision analysis in therapeutic strategies for small bowel obstructions]. AB - Clinical decision analysis was applied in therapeutic decision-making regarding small bowel obstructions. For strangulation obstruction, the three strategies of immediate surgery, observation of clinical course, and decision according to ultrasonographic findings were analyzed. When mortality rate, morbidity rate, or duration of hospital stay was used as the utility value, decision on the basis of ultrasonographic findings was selected as the most effective strategy, while the strategy of immediate surgery was selected when the rate of intestinal necrosis was used as the utility value. For adhesive obstructions, the three strategies of immediate surgery, conservative treatment with long tube decompression, and long tube decompression with enteroclysis (infusion contrast radiography) were analyzed. The strategy of enteroclysis was selected when morbidity rate and duration of hospital stay were used as utility values, while immediate surgery was selected when recurrence rate of adhesive obstruction was used as the utility value. For obstruction caused by intraabdominal recurrent cancer, operative treatment and conservative treatment were analyzed. The strategy of surgery was selected when rate of obstruction resolved and number of months of survival were used as utility values. Clinical decision analysis is valuable in quantitatively assessing individual variables affecting therapeutic decision-making. PMID- 1435693 TI - [Lymphoid infiltration of colon cancer and clinical significance of the skin test]. AB - It was reported that lymphoid infiltration (LI) of colon cancer tended to be found more commonly in patients with colonic cancer in an early stage than in an advanced stage. This time, the correlation among LI of colon cancer, cell mediated immunity and the cumulative 5-year survival rate was studied in 124 patients with resected colon cancer. The results were as follows: 1) The cumulative 5-year survival rate in patients with positive LI was higher than that in the patients with negative LI. 2) There was correlation between the degree of LI of the cancer and Su-PS skin reaction. 3) Postoperative cell-mediated immunity was reduced in the cases of poor prognosis. Therefore we insist on paying attention to immunochemotherapy for 24 months after surgery. PMID- 1435694 TI - [Immunohistochemical detection of p53 in colorectal cancer and its relationship to prognosis]. AB - The expression of p53 in colorectal tumors was studied immunohistochemically by monoclonal antibody (PAb1801). No nuclear staining was evident in the tumor cells of colorectal adenomas. p53 immunoreactivity was found in 59 (61.5%) of 96 colorectal cancers. There was no significant correlation between the p53 immunoreactivity and histologic type, tumor size, invasion of bowel wall, lymphatic invasion, venous invasion, lymph node metastasis, peritoneal dissemination, or liver metastasis. However, the p53 negative tumors showed a recurrence rate of 3.3%, while for the p53 positive tumors a recurrence rate of 20.9%. p53 negative tumors were associated with favorable prognosis, whereas those with p53 positive tumors were related to poor prognosis. DNA polymerase alpha positive cells rate in p53 positive tumors was significantly higher than in p53 negative tumors. The results suggested that p53 immunoreactivity might possibly be a useful prognostic marker of colorectal cancers. PMID- 1435695 TI - [The effect of hyperthermia against pancreatic cancer cell--various examinations including flow cytometric bromodeoxyuridine/DNA analysis]. AB - We investigated the effect of hyperthermia against pancreatic cancer cell in various aspects including of cytokinetics. The hyperthermia above 43 degrees C was thought to have strong effect for the studies on surviving cell number and morphological change of Capan-2 and RWP-1 cells after heating treatment. The cell inoculated to the nude mice subcutaneously after heating treatment at 43 degrees C was recognized the tumor forming at 3 weeks later, however, the growth speed was slower than that of control to which untreated Capan-2 cells were inoculated. As the case of 44 degrees C, the tumor forming was not recognized at all. The cytokinetics was measured by flow cytometric bromodeoxyuridine (BrdUrd)/DNA analysis. Up to 43 degrees C in accordance with increase in the heating temperature, the accumulation in G2M phase increased, and the amount of BrdUrd incorporated 5 phase decreased. At the temperature above 44 degrees C, BrdUrd was hardly incorporated into S phase cells and the cell cycle was almost stopped. These results suggested the usefulness of hyperthermia and strong effect of heating treatment above 44 degrees C against pancreatic cancer cell. PMID- 1435696 TI - [Preoperative diagnosis of internal mammary node metastases in patients with breast cancer by using ultrasonography]. AB - US findings of 81 patients with breast cancer were analyzed respectively to evaluate the usefulness of US in the preoperative diagnosis of internal mammary mode metastases. The internal mammary area (I.M.A.) in which internal mammary nodes lie was shown as a hypoechoic stripe in a sagittal scan along the sternum and as a triangular or spindle-shaped hypoechoic area in a transverse scan in the intercostal space. The US features of each I.M.A. in the first three intercostal spaces were divided into three patterns: Pattern-A wad defined as widening of the ipsilateral side of the I.M.A. compared with the contralateral side; Pattern-C was defined as normal at both sides of the I.M.A. Pathological examination confirmed the node metastases in 85.7% of intercostal scans showing Pattern-A and in 35% of intercostal scans showing Pattern-B. Only one of 189 intercostal scans showing Pattern-C had nodal metastases. The overall accuracy was 88.1% in 243 intercostal scans and 90.1% in 81 patients. We conclude that US is useful in the detection of internal mammary node metastases in patients with breast cancer. PMID- 1435697 TI - [Coronary artery bypass surgery in the elderly]. AB - In recent years it has become apparent that the number of persons 70 years of age or older is increasing. Between June, 1980, and December, 1990, 75 patients 70 years of age and older (range, 70-79 years; mean 73.1) underwent isolated coronary artery bypass grafting (CABG). During this same interval, 507 patients less than 70 years old underwent isolated CABG. Preoperative status in the elderly showed a significantly greater prevalence of women, urgent or emergent operation, triple vessel disease and diabetes. Operative mortality was higher among the elderly compared with the younger patients (p < 0.05). The increased frequency of urgent or emergent operation in the elderly was associated with postoperative complications. Major complications related CABG in the elderly were serious cerebrovascular accidents and low cardiac output syndrome. In order to improve the results of CABG in the elderly, it is essential to perform the elective operation following careful evaluation of both cardiac function and central nervous system. PMID- 1435698 TI - [Experimental study of the prostacyclin production of autogeneous vein graft]. AB - In order to investigate the blood compatibility of autogenous vein graft (AVG), changes in prostacyclin (PGI2) production following harvesting and arterial implantation were studied experimentally. Basal PGI2 production, which means the value obtained without stimulation by arachidonic acid (AA), decreased significantly 60 minutes after harvesting. At this time, no morphological changes in the endothelial cells were observed. Under stimulation by AA, a significant decrease in the PGI2 production of the specimens was seen 120 minutes after harvesting. Despite severe morphological changes in endothelial cells, the PGI2 production of vein grafts was maintained until this time. The AVG in the canine abdominal aorta was completely reendothelialized 1 week after implantation, but another 2 weeks were needed to restore PGI2 production. It is concluded from these results: 1. It is rational to implant an AVG within 60 minutes after harvesting from the viewpoints of morphology and PGI2 production of the endothelial cells. 2. PGI2 production from sources other than endothelial cells is possible and may contribute to the compatibility of the AVG in the early period after implantation. 3. AVG in the aorta could restore PGI2 production 3 weeks after implantation. PMID- 1435699 TI - [Oxidized cellulose occlusion of a peripheral bronchial fistula communicating to the left subphrenic abscess]. AB - A 52-year-old man was complicated with a left subphrenic abscess after total pancreatectomy and gastrectomy for advanced pancreatic cancer. A left subphrenic silicon tube penetrated the diaphragm and the bottom of the left lung as well, causing a bronchial fistula with bilateral aspiration pneumonia. Then bronchoscopically, the fistula was successfully treated by packing a few pieces of oxidized cellulose into the affected bronchus. One month later the patient died of sepsis due to multiple liver abscess. On autopsy, the bronchial fistula and any active inflammation were not recognized in the left lower lung area. PMID- 1435700 TI - [Basic study on intraoperative radiofrequency ablation by needle electrode]. PMID- 1435701 TI - [Effects of Ca2+ antagonists on the remaining liver after hepatectomy associated with ischemia: preliminary report]. PMID- 1435702 TI - [A probable relevance of desmosome to lymph node metastasis in esophageal cancer]. PMID- 1435703 TI - [The comparison of postoperative multiple organ failure with arterial disease to that with gastrointestinal cancer]. AB - The clinical features of 22 postoperative multiple organ failure (MOF) patients, comprised of 8 with arterial disease (A-MOF) and 14 with gastrointestinal cancer (G-MOF), were investigated. Differences in the operative time, blood loss, and mortality were not significant. The initial organ impaired was the lungs in 78.6% of G-MOF patients and the heart or kidneys in all A-MOF patients. Infection developed in over 80% of both groups. In many A-MOF patients, the pneumonia or septicemia developed secondary to organ failure, while intraabdominal infection triggered respiratory failure in many G-MOF patients. Our organisms in infected specimens and their antibiotic sensitivities was valuable for the early administration of effective antibiotics. Upper gastrointestinal tract bleeding was important in the prognosis of both groups and occurred more frequently in A MOF than in G-MOF patients. Consumption coagulopathy in A-MOF patients and DIC induced by infection in G-MOF patients mainly caused such bleeding. Preoperative administration of heparin was effective in improving coagulopathy. Furthermore, measurement of intramural pH with tonometer in the stomach and gastric irrigation with oxygenated perfluorochemicals were effective in the prediction and prevention of gastrointestinal bleeding. PMID- 1435704 TI - [Principles of lymphadenectomy for gastric cancer according to depth of wall invasion, tumor site and regional lymphatic flow]. AB - The principles of lymphadenectomy for gastric cancer are discussed based on the 1010 gastric cancer patients who underwent gastrectomy with curative intent between 1970 and 1990. In 147 of these patients, regional lymphatic flow was examined by injecting activated carbon particles CH40. 1) One hundred and ninety patients (19.8%) with cancer invasion confined to the mucosa had lymph node metastases limited to the perigastric nodes (n1). 2) Two hundred and five patients (20.3%) had cancer invasion to the submucosa. For 99.0% of them the lymph node metastases were limited to compartment II (n2). 3) Three hundred and twenty-two patients (31.9%), with cancer invasion to the muscle layer or serosa and limited to the upper or middle third of the stomach, had lymph node metastases in compartment II and No. 12 (n 2 + No. 12). 4) Two hundred and ninety three patients (29.0%) with cancer invasion to the muscle layer or serosa and limited to lower third of the stomach or to its extension, had lymph nodes metastases in compartment III (n3). 5) Consequent to observations on the regional lymph flow of the stomach by CH40, we now perform paraaortic lymph node dissection, when gastric cancer patients with serosal invasion have metastases lymph nodes No. 2, 7, 8a, 9, 11, 12 or No. 14V. PMID- 1435705 TI - [Relationship between prolonged life span and changes of serum IAP and albumin induced by the therapy of lentinan plus tegafur in inoperable and recurrent gastric cancer]. AB - Relationship between prolonged life span and changes of serum IAP and albumin induced by the therapy of lentinan plus tegafur were analysed on 43 cases with inoperable and recurrent gastric cancer. Antitumor effect was observed only in one case (2%). Other clinical effects such as improvement of performance status (PS), appetite or pain were observed in 18 cases (42%). Decrease of serum IAP was observed in 25 cases (58%) and increase of albumin was observed in 20 cases (47%). The changes of these two factors seemed to be reversely correlated. Among 30 cases which didn't show decrease of albumin, we found no increase of serum-IAP in 22 cases (72%). In the cases which showed decrease of serum IAP from abnormally high level (more than 500 mu/ml) and increase of albumin from abnormally low level (less than 3.5g/dl), prolonged life span was observed by comparison with the other cases. The cases with any clinical effect contained 78% of the cases without increase of serum IAP, and 72% of the cases without decrease of albumin. These results suggested that life prolongation effect or improvement of clinical symptoms by our therapy was closely related to the change of these serum factors. PMID- 1435706 TI - [Experimental study on catheter-bypass between superior mesenteric and hepatic hilar portal veins (SMV-HPV bypass)]. AB - Hepatic ischemia is a consequence of concomitant resection of the portal vein and the hepatic artery when it is necessitated in hepatobiliary or pancreatic surgery. We developed an antithrombogenic catheter with a balloon and experimentally evaluated the safety of construction of SMV-HPV bypass using this catheter to simultaneously prevent intestinal vascular congestion and hepatic ischemia. The main portal vein and the hepatic artery were blocked and SMV-HPV shunting was made in five dogs (bypass group); the main portal vein and the hepatic artery were blocked and the SMV was shunted to the femoral vein in others (ischemia group). In the ischemia group, 3 of the 5 dogs died within 5 days, but all animals of the bypass group survived for a long period. In the bypass group, the changes of adenine nucleotide levels, energy charge ratio, liver function, blood coagulation, and fibrinolysis were mild and within physiologic ranges, and none of changes of the hepatic tissue were observed histologically. This bypass procedure is simple and safe to simultaneously prevent hepatic ischemia and intestinal vascular congestion in cases requiring concomitant resection and reconstruction of the portal vein and the hepatic artery. PMID- 1435707 TI - [Establishment of an experimental model with a high frequency of liver metastasis and recurrence from gastric VX2 cancer: histological analysis of the developmental process of primary and metastatic cancer lesions]. AB - An experimental model with a high frequency of liver metastases and recurrence was established by the non-resection and resection of gastric cancer lesions induced with implanting VX2 cancer cells into the stomach of 35 rabbits. The frequency of liver metastases was 0% on Days 7 and 14, 40% on Day 21 and 60% on Day 28 in the non-resection group. In the resection group, primary lesions were resected on Days 7, 10 and 14, and the metastases were found in all the animals 14 days after the resection on Day 14, though they did not occur in every animal 18 and 21 days after the resection on Days 10 and 7. The metastatic lesions were found in the peri-lobular area, accompanied by cancer emboli in the interlobular veins. Vascular invasion was found in almost all (90%) the primary lesions of animals with liver metastases or recurrence. These results suggest that hepatic micrometastases occur between 10 and 14 days after implantation, and that vascular invasion plays an important role in the formation and extension of liver metastases or recurrence. They also suggest that this model is utilized as a useful tool for studying many aspects of liver metastases or recurrence in gastric cancer. PMID- 1435708 TI - [Investigation of lipid peroxidation in regenerating rat liver]. AB - The purpose of this study was to estimate the effects of lipid peroxidation in regenerating rat liver. Partial 70% hepatectomy was performed in rat according to Higgings and Anderson. EPC (alpha Toc: Ascorbic acid = 6:4, radical scavenger) was injected intravenously (5mg/kg weight) one hour before operation. Lipid peroxidation in regenerating liver reached a peak at 24 hours after operation. The administration of EPC markedly suppressed the increase of lipid peroxide in the plasma and remnant liver and that of GPT after hepatectomy, with subsequent good liver regeneration ratio. Moreover, the pretreatment with EPC remarkably elevated the activity of thymidine kinase (index of DAN synthesis). The EPC administration had not notable effects on the level of plasma ketone body ratio in animal but pathologically caused early advent of glycogen granule in the remnant liver tissue after partial hepatectomy, which reflected restoration of mitochondrial energy level. The results of the present study suggest that scavenger may be useful not only for impairment of liver dysfunction but also for recovery of mitochondrial energy level and DNA synthesis after liver resection. PMID- 1435709 TI - [Experimental study of hepatic inflow occlusion in extrahepatic obstructive jaundice--effects on systemic and hepatic hemodynamics and oxygen metabolism]. AB - The effect of clamping both the hepatic artery and portal vein for 20 min in extrahepatic obstructive jaundice on systemic and hepatic hemodynamics and oxygen metabolism were studied in dogs, and the following results was obtained. 1) Dogs with obstructive jaundice were in a hyperdynamic state before hepatic inflow occlusion, showing an increased demand for oxygen in the liver. 2) After declamping, cardiac index and systemic oxygen delivery were decreased in normal dogs, but a further decrease was found in dogs with jaundice. 3) After declamping, hepatic arterial blood flow was increased in normal dogs. Portal blood flow was decreased just after declamping, but was soon restored. In dogs with jaundice, hepatic arterial blood flow increased to a lesser extent, and recovery of portal blood flow was delayed. 4) Hepatic oxygen consumption and oxygen extraction ratio were already increased markedly just after declamping in normal dogs, whereas the degree of the increase in these parameters was much smaller in dogs with jaundice. Thus, hepatic inflow occlusion in extrahepatic obstructive jaundice induces evident disorder of hepatic oxygen metabolism, and is suggested to be dangerous. PMID- 1435710 TI - [A study of phagocytic cell function in aspiration pneumonia induced by carrageenan]. AB - To estimate the changes in phagocytic cell function associated with aspiration pneumonia, induced in mice by intra-tracheal injection of carrageenan. In inflammatory sites, the dominant increased cell component was polymorphonuclear leukocytes (PMNs). Intracellular 2'-7'-dichlorofluorescein (DCFH) oxidation of PMNs infiltrated into the lung tissue of the carrageenan-treated mice revealed a lower level of activity than that of a control group throughout a 120-hour period. The DCFH oxidative activity of alveolar macrophages (AMs) was lower in the broncho-alveolar lavage fluid and lung tissue of the carrageenan-treated mice than the control group. A decrease in the DCFH oxidative activity of AMs was observed after treatment with KCN or deferoxamine in the control group. In contrast, activity in the carrageenan-treated group was not decreased by KCN. Moreover, increased expression of Ia and F4/80 antigens was detected in the AMs of the carrageenan-treated group. These results show that increasing numbers of PMNs have a major role as phagocytic cells in inflammatory lung tissue, whereas AMs are reduced to their oxidative product and change into antigen-presenting cells, revealing a high ratio of Ia expression. The decrease in DCFH oxidation in the AMs of the carrageenan-treated mice may have been due to decreased mitochondrial oxidative metabolism. PMID- 1435712 TI - [The utility of new model Swan-Ganz catheter (REF-1) in postoperative fluid management of patients who underwent radical operation for esophageal cancer: preliminary report]. PMID- 1435711 TI - [A case of minimal-sized adenocarcinoma in a fistula-in-ano]. AB - The patient was 47 year-old man with a simple intermuscular fistula-in-ano. Fistulectomy revealed that there was a small mucinous adenocarcinoma. The tumor was small and localized in the wall of the fistula and the muscular invasion was not recognized. The mucin contained a little O-acylated sainomucin, and the origin of the tumor was considered as anal gland cell. This case appears as one evidence that the cancer in fistula-in-ano originates from the anal gland cell in the fistula. PMID- 1435713 TI - [Enhancement effect of fat emulsion for intravenous use (intralipos) on the growth of a human breast cancer cell line in culture: preliminary report]. PMID- 1435714 TI - [Effect of local administration of 15-deoxyspergualin on liver allografts in the rat: preliminary report]. PMID- 1435715 TI - [The modulation of intracellular folate level by leucovorin: preliminary report]. PMID- 1435716 TI - [Effect of preoperative supplemental hyperalimentation on patients with upper gastrointestinal malignancies: preliminary report]. PMID- 1435717 TI - [Measurement of the chemiluminescence from rat hepatocytes on reperfusion injury: preliminary report]. PMID- 1435718 TI - [Type IV collagenase activities in human colorectal carcinomas and its role in hepatic metastasis: preliminary report]. PMID- 1435719 TI - [A fundamental study on photodynamic therapy of pancreatic tumor in rabbit: preliminary report]. PMID- 1435720 TI - [Tumor marker (CA19-9, DU-PAN 2, SPAN 1) levels in cystic fluid of benign liver cyst: preliminary report]. PMID- 1435721 TI - Purification and properties of the RuvA and RuvB proteins of Escherichia coli. AB - The RuvA and RuvB proteins of Escherichia coli play important roles in the post replicational repair of damaged DNA, genetic recombination and cell division. In this paper, we describe the construction of over expression vectors for RuvA and RuvB and detail simple purification schemes for each protein. The purified 22 kDa RuvA polypeptide forms a tetrameric protein (M(r) ca. 100,000) as observed by gel filtration. The tetramer is stabilised by strong disulphide bridges that resist denaturation during SDS-PAGE (in the absence of boiling and beta mercaptoethanol). In contrast, purified RuvB polypeptides (37 kDa) weakly associate to form a dimeric protein (M(r) ca. 85,000). At low protein concentrations, the RuvB dimer dissociates into monomers. The multimeric forms of each protein may be covalently linked by the bifunctional cross-linking reagent dimethyl suberimidate. Addition of purified RuvA and RuvB to a RecA-mediated recombination reaction was found to stimulate the rate of strand exchange leading to the rapid formation of heteroduplex DNA. PMID- 1435722 TI - GEBF-I in Drosophila species and hybrids: the co-evolution of an enhancer and its cognate factor. AB - The activation of the Drosophila melanogaster salivary gland secretion protein gene Sgs-3 is marked by important changes in chromatin structure in the distal regulatory region at -600 bp from the Sgs-3 start site. A stage- and tissue specific glue enhancer binding factor, GEBF-I, binds in vitro to sequences from this region. Previous studies have revealed considerable variation in the DNA sequences of comparable regions in the related Drosophila species, D. simulans, D. erecta and D. yakuba. We detected GEBF-I-like proteins in these species, which appear to evolve as rapidly as the corresponding DNA sequences, and studied in detail the binding characteristics of the GEBF-I proteins of the two most closely related species, D. melanogaster and D. simulans. In crosses between these species, certain strains produce hybrid larvae which, unexpectedly, synthesised a single intermediate form of the protein. This suggests that the factor is subject to species-specific post-transcriptional modifications. In these hybrid larvae, which carry one D. melanogaster and one D. simulans Sgs-3 gene, the hybrid GEBF-I protein appears equally effective in the induction of both target genes. PMID- 1435723 TI - Functional conservation between Schizosaccharomyces pombe ste8 and Saccharomyces cerevisiae STE11 protein kinases in yeast signal transduction. AB - In fission yeast (Schizosaccharomyces pombe), the mat1-Pm gene, which is required for entry into meiosis, is expressed in response to a pheromone signal. Cells carrying a mutation in the ste8 gene are unable to induce transcription of mat1 Pm in response to pheromone, suggesting that the ste8 gene product functions in the signal transduction pathway. The ste8+ gene encodes a 659 amino acid putative protein kinase, which is identical to the previously identified byr2 suppressor of the ras1 defect. Furthermore, ste8+ is highly homologous to the Saccharomyces cerevisiae STE11 gene, which functions in signal transduction in budding yeast. Expression of the S. cerevisiae STE11 gene in S. pombe ste8 mutants restores the ability to transcribe mat1-Pm in response to pheromone. Also, such cells become capable of conjugation and sporulation. When mat1-Pm is artifically expressed from a heterologous promoter, ste8 mutant cells will enter meiosis. This demonstrates that the meiotic defect of ste8 mutants is due to the absence of the mat1-Pm gene product. PMID- 1435725 TI - Serum lactate dehydrogenase isoenzyme 1 activity in patients with testicular germ cell tumors correlates with the total number of copies of the short arm of chromosome 12 in the tumor. AB - The aim of our study was to assess the relationship between the serum lactate dehydrogenase isoenzyme 1 (S-LDH-1) activity in patients with testicular germ cell tumors and the number of copies of the short arm of chromosome 12 (12p) present in tumor. Twenty-seven adult patients with measurable tumor lesions were studied. Twenty-five had three or more copies of chromosome 12 per cell in the tumors. Nineteen had one or more copies of a specific chromosomal abnormality, an isochromosome of the short arm of chromosome 12, i(12p). Fourteen had increased S LDH-1 levels. S-LDH-1 activity correlated significantly with the product of total tumor volume and the total number of copies of the short arm of chromosome 12 present per cell (total tumor 12p). We conclude that the total number of copies of the short arm of chromosome 12 in the tumors is most probably a factor contributing to the LDH-1 activity released from the tumors. PMID- 1435724 TI - FinOP repression of the F plasmid involves extension of the half-life of FinP antisense RNA by FinO. AB - The transfer operon of the F plasmid is positively regulated by the traJ gene product, expression of which, in turn, is regulated by both an antisense RNA, FinP, and the FinO protein (the FinOP system). A finP- F plasmid, pSFL20, was constructed by site-directed mutagenesis and was found to produce wild-type levels of pili encoded by the transfer operon. Transcription of the traJ gene was decreased by a factor of 3-5 fold in the presence of FinOP with no accumulation of a stable RNA duplex between the FinP RNA and the portion of the traJ mRNA which is complementary to finP. Stabilization of FinP RNA by FinO occurs in the absence of traJ transcripts, suggesting that FinO may interact directly with FinP to prevent its degradation. PMID- 1435726 TI - Cloning and molecular characterization of the secY genes from Bacillus licheniformis and Staphylococcus carnosus: comparative analysis of nine members of the SecY family. AB - SecY is a central component of the export machinery that mediates the translocation of secretory proteins across the plasma membrane of Escherichia coli. We have cloned and sequenced the secY genes from Bacillus licheniformis and Staphylococcus carnosus. The deduced amino acid sequences are highly homologous to those of other known SecY polypeptides, all having the potential to form 10 transmembrane segments. Comparative analysis of 9 SecY polypeptides, derived from different bacteria, revealed that 14 amino acid positions (2.7%) are identical in all SecY proteins and 89 (16.9%) show conservative changes. Clusters of conserved amino acid residues were found in 4 of the 10 transmembrane segments and 2 of the 6 cytoplasmic domains. It is suggested that the conserved regions might be involved in the translocation activity of SecY or might be required for the correct interaction of SecY with other components of the secretion apparatus. PMID- 1435727 TI - Characterization of a chromosomally encoded, non-PTS metabolic pathway for sucrose utilization in Escherichia coli EC3132. AB - A wild-type isolate, EC3132, of Escherichia coli, that is able to grow on sucrose was isolated and its csc genes (mnemonic for chromosomally coded sucrose genes) transferred to strains of E. coli K12. EC3132 and all sucrose-positive exconjugants and transductants invariably showed a D-serine deaminase (Dsd) negative phenotype. The csc locus maps adjacent to dsdA, the structural gene for the D-serine deaminase, and contains an inducible regulon, controlled by a sucrose-specific repressor CscR, together with structural genes for a sucrose hydrolase (invertase) CscA, for a D-fructokinase CscK, and for a transport system CscB. Based on DNA sequencing studies, this last codes for a hydrophobic protein of 415 amino acids. CscB is closely related to the beta-galactoside transport system LacY (31.2% identical residues) and a raffinose transport system RafB (32.3% identical residues) of the enteric bacteria, both of the proton symport type. A two-dimensional model common to the three transport proteins, which is based on the integrated consensus sequence, will be discussed. PMID- 1435728 TI - Differential manifestation of seed mortality induced by seed-specific expression of the gene for diphtheria toxin A chain in Arabidopsis and tobacco. AB - A pea vicilin promoter-diphtheria toxin A (DTx-A) chain gene fusion was introduced into Arabidopsis and tobacco. The chimeric Dtx-A gene behaves as a dominant, seed-lethal, Mendelian factor, and the segregation ratios are consistent with the numbers of integrated copies as revealed by Southern blotting. Germination deficiency results from distinct developmental abnormalities, thus allowing genetic dissection of seed development. The endosperm is affected first in both species. In Arabidopsis, full cellularization of the initially syncytial endosperm does not take place, which results in shrinkage and a shriveled appearance of the mature dry seed. The embryo, which appears structurally normal and lacks visible lesions, ceases to develop at the partially recurved cotyledon stage and does not use the remaining endosperm. In tobacco, peripheral degeneration and premature termination of cellular endosperm development occurs at the cotyledon initiation stage. Lesions appear in the cotyledons at the advanced cotyledon stage, but the embryo continues to grow and attains nearly the same size and level of differentiation as mature wild-type embryos before degeneration and intracellular disintegration take place throughout. Accumulation of protein bodies and other cytoplasmic inclusions is very limited and occurs only in few cells. The timing and distribution of lesions follow a pattern typical for accumulation of protein bodies in wild-type seeds. These observations are consistent with expression of the vicilin promoter in the enlargement phase of cell differentiation. A novel tissue interaction arises, when the embryo uses up all the arrested endosperm: the embryo proves to be capable of absorbing the parenchyma layers of the integument, which are normally obliterated by, and incorporated into, the endosperm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435729 TI - Induction of a Streptomyces cacaoi beta-lactamase gene cloned in S. lividans. AB - The previously cloned class A beta-lactamase gene (bla) of Streptomyces cacaoi was shown to be inducible by beta-lactam compounds in the host organism S. lividans. A regulatory region of 2.75 kb was identified and the nucleotide sequence determined. It contained four open reading frames (ORFs) of which only two were complete and required for induction. ORF1-ORF2 exerted a positive regulatory effect on the expression of bla. Inactivation of ORF1 or of ORF2 resulted not only in the loss of induction, but also in a 30- to 60-fold decrease in the basal (non-induced) level of beta-lactamase production. ORF1 codes for a DNA-binding protein related to the AmpR repressor/activator, which controls the expression of ampC (class C beta-lactamase) genes in several Enterobacteria. PMID- 1435730 TI - Modular structure of the FixL protein of Rhizobium meliloti. AB - FixL protein of Rhizobium meliloti is a haemo-protein kinase which activates the transcription of nifA and fixK genes via the transcriptional activator protein FixJ under microaerobic conditions. FixL and FixJ proteins belong to the family of two-component regulatory systems for which primary sequence data predicts a modular structure. We showed, using Escherichia coli as heterologous host, that FixL indeed has a modular structure. The amino-terminal hydrophobic domain is dispensable for the oxygen-regulated activity of FixL in vivo. The central cytoplasmic non-conserved domain is necessary for the oxygen-sensing function of FixL whereas it is not necessary for the activation of FixJ by FixL. We propose that, under aerobic conditions, the central domain represses the activating function associated with the carboxy-terminal conserved domain. PMID- 1435731 TI - The region essential for efficient autonomous replication of pSa in Escherichia coli. AB - Comparative analyses were made between plasmid pSa17, a deletion derivative of pSa that is capable of replicating efficiently in Escherichia coli and plasmid pSa3, a derivative that is defective for replication. By comparing the restriction maps of these two derivatives, the regions essential for replication and for stable maintenance of the plasmid were determined. A 2.5 kb DNA segment bearing the origin of DNA replication of pSa17 was sequenced. A 36 kDa RepA protein was encoded in the region essential for replication. Downstream of the RepA coding region was a characteristic sequence including six 17 bp direct repeats, the possible binding sites of RepA protein, followed by AT-rich and GC rich sequences. Furthermore, an 8 bp incomplete copy of the 17 bp repeat was found in the promoter region of the repA gene. Based on the hypothesis that RepA protein binds to this partial sequence as well as to intact 17 bp sequences, an autoregulatory system for the synthesis of RepA protein may be operative. Another open reading frame (ORF) was found in the region required for the stability of the plasmid. The putative protein encoded in this ORF showed significant homology to several site-specific recombination proteins. A possible role of this putative protein in stable maintenance of the plasmid is discussed. PMID- 1435732 TI - The PYR1 gene of the plant pathogenic fungus Colletotrichum graminicola: selection by intraspecific complementation and sequence analysis. AB - A spontaneous uridine-requiring auxotroph of Colletotrichum graminicola was recovered by selection for resistance to 5-fluoro-orotic acid. The auxotroph lacked orotate phosphoribosyl transferase (OPRTase) and was complemented with a clone from a cosmid library of C. graminicola DNA. A 3.1 kb HindIII-SalI fragment was subcloned from the cosmid and it could efficiently transform the auxotrophic strain to uridine prototrophy and integrate by site-specific recombination. This DNA fragment contains an open reading frame that is similar to OPRTase genes of the fungi Sordaria macrospora, Trichoderma reesei, Podospora anserina, and Saccharomyces cerevisiae. Based on the sequence similarities and the ability to restore uridine prototrophy, we conclude that the fragment contains the C. graminicola gene for OPRTase, which we have named PYR1. Our results demonstrate that cloning by complementation is feasible in C. graminicola, that the gene for OPRTase from C. graminicola can be useful as a selectable marker in transformation of the fungus, and that the OPRTase gene product is similar to OPRTase from other fungi. PMID- 1435733 TI - Analysis of the site of action of the amdR product for regulation of the amdS gene of Aspergillus nidulans. AB - The amdR gene of Aspergillus nidulans regulates a number of structural genes in response to omega amino acid inducers. The site of action of the amdR product on expression of the amdS gene was investigated by studying the effects of changes in the 5' region of amdS, generated in vitro, on the induction, and on responses of an amdS-lacZ fusion gene to an amdRc allele. A sequence was identified that is sufficient for amdR regulation and that shows identity with sequences involved in amdR regulation of the gatA and lam genes. This sequence includes a CCAAT sequence and it was shown that this sequence is an important element in setting the basal level of amdS expression. PMID- 1435734 TI - Suppression of the growth and export defects of an Escherichia coli secA(Ts) mutant by a gene cloned from Bacillus subtilis. AB - A gene library of Bacillus subtilis chromosomal DNA was screened for genes capable of reverting the growth defects of the Escherichia coli secA51(Ts) mutant at 42 degrees C. A B. subtilis gene, designated csaA, was found to phenotypically suppress not only the growth defects of the E. coli mutant, but also to relieve the detrimental accumulation of precursors of exported proteins. The csaA gene encoded a protein of 15 kDa (137 amino acids) and was likely to be the distalmost member of an operon. No similarity to csaA was found among DNA or protein sequences deposited in databases. In contrast to other homologous or heterologous suppressors of the E. coli secA51(Ts) mutation, the csaA gene did not exert pleiotropic effects on either the E. coli secY24(Ts) or lep9(Ts) mutations. However, it restored the ability of a SecB-deficient mutant to grow on complex medium. It is proposed that CsaA serves as a molecular chaperone for exported proteins or alternatively acts by stabilizing the SecA protein. PMID- 1435735 TI - Effect of donor copy number on the rate of gene conversion in the yeast Saccharomyces cerevisiae. AB - Nonreciprocal recombination (gene conversion) between homologous sequences at nonhomologous locations in the genome occurs readily in the yeast Saccharomyces cerevisiae. In order to test whether the rate of gene conversion is dependent on the number of homologous copies available in the cell to act as donors of information, the level of conversion of a defined allele was measured in strains carrying plasmids containing homologous sequences. The level of recombination was elevated in a strain carrying multiple copies of the plasmid, compared with the same strain carrying a single copy of the homologous sequences either on a plasmid or integrated in the genome. Thus, the level of conversion is proportional to the number of copies of donor sequences present in the cell. We discuss these results within the framework of currently favoured models of recombination. PMID- 1435736 TI - Adipocyte fatty acid-binding protein: regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. AB - Pioglitazone, a thiazolidinedione, is a novel antidiabetic compound that can lower blood glucose in diabetic rodents by increasing insulin sensitivity in target tissues. We have previously demonstrated that pioglitazone can enhance the insulin- or insulin-like growth factor-1-regulated differentiation of 3T3-L1 cells, a cell line that undergoes morphological and biochemical differentiation to mature adipocytes [Mol. Pharmacol. 41:393-398 (1992)]. In this study, we have examined the effect of pioglitazone on the expression of the adipocyte fatty acid binding protein (aFABP) in ob/ob mice and 3T3-L1 cells. Administration of the drug to mice was observed to cause a dose-dependent increase in aFABP mRNA expression in epididymal fat, which was correlated with a decrease in blood glucose and insulin levels. Treatment of 3T3-L1 cells with pioglitazone enhanced aFABP expression in a time-dependent fashion. To explore a possible direct effect of pioglitazone on aFABP expression, a chimeric gene was constructed containing the aFABP promoter fused upstream of the bacterial reporter gene for chloramphenicol acetyltransferase. After transfection into 3T3-L1 cells and selection of stable transformants, regulation of the chimeric gene was studied. Pioglitazone, in combination with insulin or insulin-like growth factor-1, was observed to elicit a dose-dependent increase in expression, indicating a role for pioglitazone in regulating transcription of the aFABP gene. Several thiazolidinedione analogs were tested for their ability to induce the expression of the chimeric gene, and it was found that activity in this assay paralleled the structure-activity relationships observed for enhancement of 3T3-L1 cell differentiation. These observations on control of aFABP gene expression by pioglitazone suggest possible mechanisms by which cellular sensitivity to insulin may be regulated. PMID- 1435737 TI - Cloning and expression of a high affinity taurine transporter from rat brain. AB - A cDNA clone (designated rB16a) encoding a taurine transporter has been isolated from rat brain, and its functional properties have been examined in mammalian cells. The nucleotide sequence of the clone predicts a 621-amino acid protein with significant homology to other neurotransmitter transporters. Hydropathy analysis reveals stretches of hydrophobic amino acids indicative of 12 transmembrane domains, similar to those proposed for other cloned neurotransmitter transporters. The transporter displays high affinity for taurine (Km approximately 40 microM) and is dependent on external sodium and chloride for transport activity. Specific transport is sensitive to inhibition by beta-alanine and gamma-aminobutyric acid, similar to taurine transporters in vivo. Localization studies demonstrate that the transporter mRNA is located in both the brain and peripheral tissues. The structural similarity of the taurine transporter to neurotransmitter transporters is consistent with a neuromodulatory role for taurine in the nervous system. PMID- 1435738 TI - Equilibrium and kinetic studies of the interactions of salmeterol with membrane bilayers. AB - The interaction of salmeterol with model membranes has been studied with regard to equilibrium and kinetic behavior, including determination of the membrane based partition coefficient, the rate of dissociation of salmeterol from membranes, and the rate of association. These data were obtained in various membrane preparations and under various conditions (e.g., temperature, cholesterol content). The compound is very lipophilic, compared with other beta 2 agonists such as salbutamol, and has a rapid association rate and a moderate dissociation rate. The equilibrium data support the assertion that the salmeterol action measured in perfused tissue involves an exo-site for nonspecific binding that may be identified with or related to the lipid bilayer. The kinetic data in unilamellar and multilamellar liposomes of synthetic lipids further suggest that the approach to the exo-site and the active site may involve components in the native system other than the lipid bilayer in which the beta 2 receptor is located. These additional components may explain the slow onset and the extraordinarily long duration of action. PMID- 1435739 TI - Mono- and diglucuronide formation from chrysene and benzo(a)pyrene phenols by 3 methylcholanthrene-inducible phenol UDP-glucuronosyltransferase (UGT1A1). AB - Mono- and diphenols of chrysene and benzo(a)pyrene are suspected substrates of a 3-methylcholanthrene (MC)-inducible phenol UDP-glucuronosyltransferase (UGT1A1). Mono- and diglucuronide formation from these compounds was studied in two systems, (a) livers of MC-treated rats (homologous expression) and (b) a Chinese hamster lung fibroblast cell line (V79) containing rat UGT1A1 cDNA and stably expressing this isozyme (heterologous expression). In liver microsomes of MC treated rats, glucuronidation of 6-hydroxychrysene was stimulated 11-fold by MC treatment. With 3,6-dihydroxychrysene, formation of its 3-hydroxy-6 monoglucuronide and of the diglucuronide was increased 24- and 310-fold, respectively. Induction factors obtained for monoglucuronide formation (but not for diglucuronide formation) were in line with published data on the increase of immunodetectable UGT1A1 protein and of its mRNA. It is suggested that the high induction factors for diglucuronide formation are the result of a combination of the induction of UGT1A1 and facilitated interaction of neighboring UGT1A1 molecules in endoplasmic reticulum membranes. Glucuronidation of 6 hydroxychrysene, 3-hydroxybenzo(a)pyrene, and 3,6-dihydroxybenzo(a)pyrene to their mono- and diglucuronides was clearly detectable in V79 cells expressing UGT1A1. However, conjugation of 3,6-dihydroxychrysene to its monoglucuronides was low and diglucuronide formation was not detectable, suggesting that UGT isozymes other than UGT1A1 are responsible for these reactions. PMID- 1435740 TI - Identification of receptor domains that modify ligand binding to 5 hydroxytryptamine2 and 5-hydroxytryptamine1c serotonin receptors. AB - Serotonin [5-hydroxytryptamine (5-HT)] receptors are distinguished pharmacologically by their characteristic affinities for agonists and antagonists. Two serotonin receptors, the 5-HT2 and 5-HT1c, share a number of pharmacologic and structural properties while differing in their affinities for certain agonists and antagonists. To identify regions of the 5-HT2 and 5-HT1c receptors important for specifying their unique pharmacology, we constructed six chimeric 5-HT2/5-HT1c receptors in which domains of each receptor were exchanged. The abilities of several drugs to inhibit [3H]mesulergine bound to the chimeric and parent receptors transiently expressed in COS-7 cells were then examined. For spiperone and haloperidol (both butyrophenones), chimeras that exchanged transmembrane (TM) domains I and II or TMs I-III had the greatest effects on binding affinity. The binding affinity of cinanserin (a cinnamanilide) was significantly changed in all the chimeras studied. In contrast, the binding of ketanserin (a 4-fluorobenzoylpiperidine) was strongly influenced by chimeras that exchanged TMs I-III (but not I and II) and by chimeras that exchanged intracellular loop 3 to TM VII. 5-HT binding affinity was greatly altered for chimeras that exchanged domains of intracellular loop 3 to TM VII, with minor effects being noted for chimeras that exchanged TMs I and II and I-III. The affinities of the nonselective drugs mesulergine, mianserin, and m chlorophenylpiperazine were relatively unaffected when domains of the 5-HT2 and 5 HT1c receptors were exchanged. Taken together, these results imply that structurally diverse 5-HT2 antagonists utilize distinct regions of the 5-HT2 receptor for high affinity binding. PMID- 1435741 TI - Two allosteric modulators interact at a common site on cardiac muscarinic receptors. AB - The abilities of gallamine, obidoxime, tetrahydroaminoacridine (THA), and 8-(N,N diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) to alter the rate of dissociation of N-[3H]methylscopolamine from rat cardiac muscarinic receptors were investigated. All four ligands monotonically slowed the dissociation, with the order of potency gallamine > TMB-8 > THA > obidoxime. There was a dramatic difference in the efficacy of these allosteric modulators. Gallamine, TMB-8, and THA slowed the dissociation of N-methylscopolamine by > 90% at maximally effective concentrations, whereas obidoxime was capable of slowing it by only about 50%. In a manner analogous to the action of a partial agonist, obidoxime was able to partially reverse the effects of the other three modulators. Furthermore, the concentration-dependent effects of combinations of obidoxime and gallamine were in good agreement with the model of competitive interaction between these two ligands. These results provide the first evidence that two muscarinic allosteric modulators interact competitively at a well defined site. PMID- 1435742 TI - Chronic lithium treatment inhibits basal and agonist-stimulated responses in rat cerebral cortex and GH3 pituitary cells. AB - Li+ is used clinically in the management of bipolar-disordered (manic-depressive) illness, but the mechanism of its clinical efficacy remains unclear. Li+ inhibits the metabolism of certain inositol phosphates, leading to a decreased cycling of inositol that may be sufficient to reduce phosphoinositide metabolism. We have tested this hypothesis in slices of rat cerebral cortex and in rat pituitary GH3 cells grown in the presence of low extracellular inositol. We show that basal and stimulated mass levels of inositol-1,4,5-trisphosphate were reduced in rat cerebral cortex and in GH3 cells after chronic, but not acute, treatment with a therapeutic concentration of Li+. In GH3 cells chronic treatment with Li+ also decreased basal levels of intracellular Ca2+ and secretion of prolactin, effects that were prevented by the presence of myo-inositol. Agonist-stimulated mobilization of Ca2+ and prolactin release were also reduced in Li(+)-treated cells. These findings show that chronic perturbation of the phosphoinositide pathway by Li+ is sufficient to reduce basal and agonist-stimulated cellular responses, an action that may underlie its effectiveness in the alleviation of affective disorders. PMID- 1435743 TI - Effect of extracellular pH on the potency of N-methyl-D-aspartic acid receptor competitive antagonists. AB - Structure-activity analysis reveals that acidic alpha-amino acids containing an omega-PO3H2 group are more potent antagonists at N-methyl-D-aspartate (NMDA) receptors than are analogs with omega-COOH or omega-tetrazole groups. At physiological values of extra-cellular pH the omega-PO3H2 group is only partially deprotonated and the corresponding antagonists exist as ions with one or two negative charges. In contrast, competitive antagonists with omega-COOH and omega tetrazole groups are fully ionized at physiological pH but carry only a single negative charge. Dose-inhibition analysis was performed with (2R)-AP7 and its piperidine derivative LY 257883 to determine whether ionization of the omega PO3H2 group influences NMDA receptor antagonist potency; these experiments revealed a > 3-fold increase in potency on raising of the extracellular pH from 7.3 to pH 8.2, consistent with the increase in the relative concentration of the ionic form of the antagonist in which the omega-PO3H2 group contains two negative charges. Experiments with the omega-COOH-containing analog of LY 257883 and with SDZ EAB 515, an omega-PO3H2-containing antagonist of novel structure, revealed only 1.5- and 1.3-fold increases in potency, respectively, over the same pH range. Analysis of the kinetics of block of NMDA-activated currents resulting from rapid application of LY 257883 suggests that the increase in potency on raising of the extracellular pH results largely from an increase in the antagonist association rate constant but also from a small decrease in the dissociation rate constant. Together, these results suggest that the fully ionized forms of the R-enantiomers of AP7 and LY 257883 act as the active antagonist species at NMDA receptors. PMID- 1435744 TI - Determinants of antifolate cytotoxicity: folylpolyglutamate synthetase activity during cellular proliferation and development. AB - Previous studies have documented the metabolism of a broad range of folate antimetabolites to polyglutamate derivatives by the enzyme folylpoly-gamma glutamate synthetase (FPGS). The activity of the more recently developed classes of antifolates directed against thymidylate synthase and de novo purine synthesis is sufficiently dependent on polyglutamation that these compounds should be specifically cytotoxic to any normal or malignant proliferating cell expressing this enzyme. We have studied the patterns of expression of FPGS in mammalian cells and tissues during rapid growth, growth arrest, differentiation, and embryonic development. During embryogenesis in the rat, FPGS levels in liver and brain were higher during the period of proliferative activity and then dropped to a level characteristic of the adult organs. However, the levels in liver were substantially higher than those in brain at any given time. This pattern was mimicked in mouse C3H 10T1/2 embryo fibroblast cells, in which FPGS activity decreased after cessation of growth but then remained at a lower steady state level during an extended period of postconfluent culture. Enzyme activity also dropped after the differentiation of human HL-60 promyelocytic leukemia cells. In a human homolog of these experimental systems, FPGS levels were below the limits of detection in circulating mature human hematopoietic cells of the granulocytic, lymphoblastic, and erythrocytic lineages. In striking contrast, substantial levels of FPGS were found in circulating lymphoblasts from eight patients with acute lymphoblastic leukemia. The levels of FPGS found in these transformed stem cells would help to explain the sensitivity of many acute lymphoblastic leukemias to folate antimetabolites. We concluded that expression of FPGS is regulated by at least two mechanisms, one of which is linked to proliferation and the other of which controls enzyme levels after differentiation and is tissue specific. PMID- 1435745 TI - Regiochemical differences in cytochrome P450 isozymes responsible for the oxidation of methylenedioxyphenyl groups by rabbit liver. AB - The cytochrome P450 isozymes catalyzing the oxidation of the methylenedioxyphenyl compounds methylenedioxybenzene (MDB) and methylenedioxyamphetamine (MDA) have been investigated in rabbit liver preparations. The aromatic ring in MDB undergoes both demethylenation to catechol and aromatic hydroxylation to sesamol, whereas that in MDA undergoes only demethylenation to dihydroxyamphetamine. Formation of catechol and sesamol from MDB in microsomal incubation mixtures was enhanced about 5- and 3-fold, respectively, by pretreatment of the rabbits with phenobarbital, which induced CYP2B4 and CYP4B1. The cytochrome P450 isozyme responsible for aromatic hydroxylation of MDB was induced by beta-naphthoflavone and was inhibited by alpha-naphthoflavone. Microsomal demethylenation of MDA was minimally sensitive to pretreatment of the rabbits with phenobarbital, beta naphthoflavone, pyrazole, or rifampicin. However, MDA competitively inhibited the N-demethylation of erythromycin. Antibodies against CYP2B4, but not those against CYP4B1, caused a marked inhibition of the demethylenation and aromatic hydroxylation of MDB. Antibodies against CYP2C3 did not inhibit the demethylenation of MDA, nor did substrates or inhibitors of the CYP2D family except for bufuralol. MDB and MDA were both capable of forming metabolic intermediate complexes, and the rate of complex formation was accelerated by phenobarbital induction. Reconstitution experiments with CYP2B4 suggested that phenobarbital-inducible complex formation from MDA was not due to the carbene pathway involving the methylenedioxy group but was due to oxidation of the amino group. These results indicate that CYP2B4 oxidizes different regions of methylenedioxyphenyl compounds depending on their structure. MDB undergoes oxidation at the methylenedioxy group (major) and the benzene ring (minor). MDA is oxidized at the alkylamino side chain at the nitrogen and alpha-carbon. The results suggested that one or more constitutive isoforms (probably unknown) of cytochrome P450 present in rabbit liver microsomes are primarily responsible for MDA demethylenation but that CYP3A6 contributes slightly. PMID- 1435746 TI - Cellular pool of transient ferric iron, chelatable by deferoxamine and distinct from ferritin, that is involved in oxidative cell injury. AB - A cellular pool of transient ferric iron that is chelatable by deferoxamine, distinct from ferritin, and required for oxidative cell injury has been identified in cultured rat hepatocytes labeled with 59FeCl3. Pretreatment of hepatocytes with deferoxamine depleted the cellular pool of chelatable iron and protected the cells from an oxidative injury. Incubation of deferoxamine pretreated hepatocytes in serum-free medium restored both the chelatable iron pool and the susceptibility to oxidative injury. Furthermore, inhibition of protein degradation with chymostatin prevented the restoration of both the chelatable pool and susceptibility to oxidative injury. The deferoxamine chelatable iron pool was distinguished kinetically and immunochemically from the larger cellular pool of ferritin iron. The labeled iron in the deferoxamine chelatable pool was transient, unlike either the total cellular uptake of 59Fe or its incorporation into ferritin, both of which increased with time of labeling. With pulse-chase labeling, the percentage of the total uptake of 59Fe that was represented by the deferoxamine-chelatable pool decreased. At the same time, the percentage represented by radioactivity immunoprecipitable as ferritin increased. Furthermore, immunoprecipitation of ferritin from the labeled lysates enriched the resulting immunosupernatants in deferoxamine-chelatable iron. The degree of enrichment for chelatable iron correlated with the percentage of the cellular label that was immunoprecipitable as ferritin. The deferoxamine-chelatable iron appears to represent a metabolically common pool of iron that is rapidly in transit through the cell. Extracellular iron entering the pool can be utilized for heme synthesis or stored in ferritin, whereas protein degradation releases storage iron into this pool. PMID- 1435747 TI - Hypersensitivity to acetaldehyde-protein adducts. AB - Acetaldehyde, the first product in the metabolism of ethanol, is known to condense with plasma proteins, forming stable adducts. We have previously shown that these adducts can be recognized as foreign by the immune system. In the present study the existence of type I hypersensitivity-mediating antibodies against these adducts was investigated in humans and in animals. Immunization of mice with acetaldehyde-protein condensates, followed by adoptive transfer of splenocytes, led to the production of IgE anti-acetaldehyde adducts. A monoclonal IgE antibody was obtained by the hybridization technique. This antibody recognized acetaldehyde adducts, independently of the carrier protein used, indicating that the acetaldehyde moiety behaves as a hapten. The affinity of the antibody for the acetaldehyde adduct of polylysine was 7 orders of magnitude higher than that for polylysine. Passive immunization by intradermal or intravenous administration of this monoclonal antibody to rats rendered the animals hypersensitive to acetaldehyde-protein conjugates, as shown by marked anaphylaxis. A study was conducted to determine the existence of naturally occurring hypersensitivity reactions to alcohol in > 1000 non-Oriental individuals. A prevalence of severe hypersensitivity reactions of 0.46% was found. The reactions were severe enough to deter these individuals from consuming all types of alcoholic beverages. Individuals presenting such reactions had significantly elevated levels of circulating anti-acetaldehyde-protein IgE antibodies. PMID- 1435748 TI - Correlations between the rate constant of singlet oxygen quenching by imidazole derivatives and anti-inflammatory activity in rats. AB - The second-order rate constants, k delta, for quenching of molecular singlet oxygen O2 (1 delta g) by nonsteroidal anti-inflammatory imidazole drugs have been determined using time-resolved phosphorescence detection of singlet oxygen. A linear correlation was observed between log k delta (ranging from 7.90 to 8.50) and the anti-inflammatory activity of these compounds (ranging from ED50 = 15 to 300 mg/kg), as measured in rats by Jorgensen and Dyrsting [United States Patent 4,424,229 (1984)]. The correlation between this physico-chemical parameter measured in vitro and a biological activity measured in vivo might be useful in screening other types of candidate anti-inflammatory drugs. The rate constant (k delta) can be considered as a quantitative expression of the electron-donating power of the imidazole drug, as suggested by a correlation of log k deta (ranging from 6.02 to 7.45) with Hammett substituent parameters observed in the case of 2 substituted imidazoles. PMID- 1435749 TI - Epidermal growth factor activates phospholipase C in rat hepatocytes via a different mechanism from that in A431 or rat1hER cells. AB - Epidermal growth factor (EGF) can stimulate inositol lipid hydrolysis in rat hepatocytes and can accelerate GTP/GDP exchange in hepatic membranes. Both of these responses can be abolished by pretreatment with pertussis toxin, suggesting that EGF may regulate phospholipase C (PLC) activity via a guanine nucleotide binding regulatory protein (G protein) in liver cells. In contrast, in A431 human epidermoid carcinoma cells EGF can induce a rapid phosphorylation of PLC-gamma on tyrosine residues that increases the activity of immunoprecipitated PLC-gamma, suggesting that tyrosine phosphorylation of PLC-gamma may be the mechanism for EGF-stimulated inositol trisphosphate production in these cells. To determine the importance of the phosphorylation of PLC-gamma on tyrosine residues in a system where the EGF receptor apparently couples to a G protein, the effect of EGF on tyrosine phosphorylation of PLC-gamma was examined in rat hepatocytes. PLC-gamma was immunoprecipitated from cell lysates with a PLC-gamma antiserum and its tyrosine phosphorylation state was determined using both Western blot analysis with phosphotyrosine antibodies and direct measurement of phosphorylated amino acids. The results were compared with analogous experiments performed with A431 cells and another cultured cell line expressing high levels of human EGF receptors, Rat1hER fibroblasts. Although the amount of PLC-gamma in rat hepatocytes is similar to that in A431 cells and slightly higher than that in Rat1hER cells, EGF causes a barely detectable increase in the phosphorylation of PLC-gamma on tyrosine in hepatocytes, whereas it stimulates a significant degree of phosphorylation of PLC-gamma on tyrosine in Rat1hER or A431 cells. Pretreatment of hepatocytes with pertussis toxin abolishes the ability of EGF to activate PLC, as determined by an increase in intracellular Ca2+, but has no effect on the small amount of phosphate incorporated into tyrosine residues on the PLC-gamma protein, demonstrating that this low level of PLC-gamma phosphorylation does not correlate with changes in PLC activity. The data suggest that phosphorylation of PLC-gamma on tyrosine is not important for EGF-enhanced PLC activity in hepatocytes. This conclusion implies that EGF may use a mechanism to regulate PLC activity in hepatocytes that is different from that used in cultured cells expressing high levels of EGF receptors. PMID- 1435750 TI - Peptide inhibitors of ADP-ribosylation by pertussis toxin are substrates with affinities comparable to those of the trimeric GTP-binding proteins. AB - Pertussis toxin (PTX) ADP-ribosylates alpha subunits of GTP-binding proteins (G proteins) when they are in association with beta gamma dimers, and free alpha subunits are thought not to be substrates under standard assay conditions. We now report the rather unexpected discovery that synthetic peptides encompassing the last 10-20 amino acids of alpha subunits of PTX-sensitive G proteins are substrates for PTX by themselves and in the absence of beta gamma dimers. As determined for G13, the Km of PTX for the 20-amino acid carboxyl-terminal peptide is 10-fold higher than that for the trimeric G protein. Interestingly, PTX ADP ribosylates the free full length alpha 13 subunit with a Km not different from that of the trimer but with a Vmax that is only 1% of that with which it ADP ribosylates the trimer. It follows that the primary role of beta gamma dimers in ADP-ribosylation of G proteins is one of increasing the Vmax of the reaction without affecting the Km of the substrate for the toxin. Mutant peptides lacking the ADP-ribose acceptor site act as competitive inhibitors. PMID- 1435751 TI - Indirect effect of guanine nucleotides on antagonist binding to A1 adenosine receptors: occupation of cryptic binding sites by endogenous vesicular adenosine. AB - Guanine nucleotides such as guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) have been found to increase the binding of antagonists to adenosine A1 receptors. This response can be attributed either to a direct effect of GTP on receptors to increase antagonist affinity or to an indirect effect to decrease the affinity of receptors for a pool of endogenous adenosine that cannot be readily removed from membranes. In this study, adenosine content was measured in preparations of membranes and 3-[(3-cholamidopropyl)dimethylamino]-1-propanesulfonate (CHAPS) solubilized receptors by a sensitive radioimmunoassay. In both preparations, pools of adenosine (2.5-10 pmol/mg of protein) were detected that were resistant to deamination by added adenosine deaminase (0.5-3 units/ml) unless membrane lipids were first dissolved in acetone. Electron microscopic examination of crude CHAPS-solubilized receptors revealed the existence of small vesicles (< 1 microns in diameter). Furthermore, most "solubilized" receptors were retained by a 0.1 microns filter. The effects of GTP gamma S were evaluated on the binding of an antagonist, 3-(4-amino-3-125I-phenethyl)-1-propyl-8-cyclopentylxanthine (125I-BW A844U), to A1 receptors of bovine brain membranes, receptors solubilized in CHAPS (crude solubilized), or receptors partially co-purified with G proteins by agonist affinity chromatography (partially purified). GTP gamma S (10 microM) increased antagonist binding to membranes (20-50%) and crude CHAPS-solubilized receptors (> 200%) but increased binding to partially purified receptors by only 10-15%. GTP gamma S decreased agonist (125I-N6-aminobenzyladenosine) binding and increased antagonist Bmax, but did not significantly decrease (5%) the dissociation rate of the antagonist. Omission of Mg2+ mimicked the effects of GTP gamma S on agonist and antagonist binding and increased both the association and dissociation rates of 125I-BW-A844U. These data suggest that a Mg(2+)-dependent GTP gamma S-induced increase in antagonist binding to membranes and solubilized receptors is primarily due to unmasking of cryptic binding sites occupied by contaminating vesicular adenosine. These findings are consistent with the observation that adenosine receptor antagonists have been found to have little or no inverse agonist physiological effects in well oxygenated tissues. PMID- 1435752 TI - Isolation and characterization of imidazoline receptor protein from bovine adrenal chromaffin cells. AB - We sought to isolate and partially purify proteins corresponding to the binding element of the imidazoline receptor (IR) from adrenal chromaffin cell membranes. These cells express IRs of the I-2 subclass and not alpha 2-adrenergic receptors. Proteins were solubilized in 3-[(3-cholamidopropyl)dimethylammonio]-1 propanesulfonate-containing buffer and were assayed by binding of [3H]idazoxan, an imidazoline radioligand. Two ligand affinity resins, p-aminoclonidine Trisacryl GF-2000 (PAC-ReactiGel) and idazoxan-PharmaLink agarose (IDA-agarose), were synthesized. These allowed purification by single-step affinity chromatography of a major receptor binding protein component of 70 kDa, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and [3H]idazoxan binding assay. The purified imidazoline-binding proteins from IDA-agarose and PAC-ReactiGel had similar affinities for the radioligand [3H]idazoxan (Kd = 3.7 and 4.9 nM, respectively) and a displacement profile, showing sensitivity to imidazoline agents (cirazoline > clonidine) and insensitivity to catecholamines and adrenergic agents (epinephrine approximately rauwolscine), that was similar to that of the intact membrane receptor. The imidazoline-binding protein did not bind to concanavalin A, suggesting that it may not be glycosylated or that the sugar moieties present are not recognized by this lectin. The results indicate that IR and alpha 2 receptor proteins may be biochemically distinct and that IDA-agarose and PAC-ReactiGel columns are useful for purification of sufficient quantities of imidazoline-binding proteins to allow for structural and functional studies of the IR. PMID- 1435753 TI - Prolonged D2 antidopaminergic activity of alkylating and nonalkylating derivatives of spiperone in rat brain. AB - Alkyl and arylalkyl derivatives of the dopamine (DA) D2 antagonist spiperone were prepared and characterized chemically and pharmacologically. They included the N methyl, N-phenethyl (NPS), and N-p-aminophenethyl (NAPS) derivatives, as well as the alkylating isothiocyanato (NIPS), bromacetamido, and ethylfumaramido p substituted N-phenethylspiperones. These compounds showed high lipophilicity (log P up to 6.0 with NIPS), as well as very high in vitro D2 affinity (Ki = 35-280 pM) and D2 versus D1 selectivity (540-9000-fold) in radioreceptor assays with corpus striatum of rat brain. Of the alkylating series, NIPS showed the highest D2 affinity (57 pM) and D2 versus D1 selectivity (2040-fold) and so was selected for further evaluation. NPS, NAPS, and NIPS showed little or no affinity for 34 non-DA binding sites defined by radioligand assays for monoamine, amino acid, and peptide neurotransmitters, ion channels, peptide growth factors, and transmission mediators but did show low alpha 2 and moderate alpha 1 and 5-hydroxytryptamine (5-HT2) affinity with rat forebrain tissue in vitro; NIPS showed a marked gain in D2 versus 5-HT2 selectivity, compared with spiperone (1520- versus 26-fold). Systemic injections of NIPS induced marked decreases in rat striatal D2 binding sites 24 hr later, with little effect on D1, 5-HT2, or alpha 1 sites; NIPS and NAPS lowered apparent Bmax values at D2 receptors with little change in ligand affinity, ex vivo as well as in vitro. NPS, NAPS, and NIPS all induced dose dependent lowering of D2 binding ex vivo (ID50 = 1-9 mumol/kg, intraperitoneally) and blocked the behavioral effects of the DA agonist apomorphine (0.9 mumol/kg) potently (ID50 = 0.3-0.5 mumol/kg) at 24 hr. Recovery from these anti-DA actions required about 1 week after equimolar (15 mumol/kg) and similarly effective doses of NPS and NAPS, as well as NIPS. Thus, highly selective and avidly bound lipophilic D2 affinity ligands with similarly avid in vitro and prolonged in vivo anti-DA activities can be derived from N-phenethylspiperones with or without an alkylating moiety present. Such affinity ligands may represent useful additions to previously used, generally less selective, D2 affinity ligands. PMID- 1435754 TI - Depletion of 5,10-methylenetetrahydrofolate and 10-formyltetrahydrofolate by methotrexate in cultured hepatoma cells. AB - The effect of the inhibition of dihydrofolate reductase by methotrexate on the cellular folates involved in de novo purine and thymidylate biosynthesis has been measured in H35 hepatoma cells grown in 4 microM folic acid or 20 nM folinic acid. The major cellular folate species in cells from medium with folate or folinate is 10-formyltetrahydrofolate (approximately 5 microM), with lesser amounts of 5,10-methylenetetrahydrofolate and tetrahydrofolate. Cultures were exposed to a pulse dose of methotrexate, resulting in the accumulation of nearly exclusively methotrexate polyglutamates (predominantly Glu3, Glu4, and Glu5), or a continuous exposure to the poorly glutamylated analog threo-4 fluoromethotrexate, resulting in 93% intracellular monoglutamate. At 4 hr and 18 hr after exposure to either compound there was extensive depletion of the reduced folate coenzymes, which generally corresponded to the extent of inhibition of glycine and deoxyuridine incorporation. This was accompanied by an increase of the cellular dihydrofolate and 10-formyldihydrofolate. In the H35 cells the effect of methotrexate polyglutamates on the reduced folate coenzyme pools was restricted to dividing cultures, because the reduced folate coenzymes were not depleted in confluent cultures. The results demonstrate that the methotrexate and methotrexate polyglutamates that initially accumulate within dividing H35 cells readily inhibit dihydrofolate reductase but are not adequate to inhibit thymidylate synthase and prevent the depletion of reduced folate coenzymes. Thus, inhibition of de novo glycine and deoxyuridine incorporation into DNA as a result of dihydrofolate reductase inhibitors appears to be closely related to a reduction in the intracellular concentration of 10-formyltetrahydrofolate and 5,10-methylenetetrahydrofolate, the respective folate coenzymes for de novo purine and thymidylate synthesis. PMID- 1435755 TI - Mechanism of inhibition of aldose reductase by menadione (vitamin K3). AB - Incubation of human placental aldose reductase (EC 1.1.1.21) with menadione (0.5 3.0 mM) resulted in time-dependent loss of the catalytic activity of the enzyme. Kinetic analysis of the data suggests that the inactivation process follows a single apparent rate constant that displays hyperbolic dependence on menadione concentration, indicating that menadione forms a kinetically significant, dissociable complex with the enzyme before the formation of an inactive enzyme menadione complex. The inactivation of the enzyme with menadione was reversed upon dialysis of the inactivated enzyme against buffer containing 10 mM dithiothreitol suggesting that menadione reacts with enzyme sulfhydryl residue(s). Inactivation of the enzyme was significantly prevented by dithiothreitol (5 mM), NADPH (0.1 mM), and DL-glyceraldehyde (10 mM). Correlation of the fractional remaining activity with the extent of modification indicates that loss of catalytic activity corresponds to the modification of a single amino acid residue of the enzyme protein. Recombinant human aldose reductase, obtained by overexpression in Escherichia coli, and aldose reductase in which Cys-80 or Cys-303 was replaced by serine were also inactivated by menadione. However, enzyme in which Cys-298 was replaced by serine was insensitive to menadione. On the basis of these observations, it is suggested that menadione forms a thiodione like adduct with Cys-298, leading to inactivation of the enzyme. PMID- 1435756 TI - Nuclear magnetic resonance spectroscopy and pattern recognition analysis of the biochemical processes associated with the progression of and recovery from nephrotoxic lesions in the rat induced by mercury(II) chloride and 2 bromoethanamine. AB - Nephrotoxic lesions were induced in Fischer 344 rats using HgCl2, a proximal tubular toxin, and 2-bromoethanamine (BEA), a medullary toxin. Biochemical effects of these toxins on urinary composition were observed by high resolution 1H NMR spectroscopy over 9 days after dosing. The onset of, progression of, and recovery from the induced toxic lesions were also followed histopathologically and related to the perturbed urinary biochemistry. Urinary concentrations of 20 endogenous substances were measured simultaneously by NMR at eight time points, to provide a time-related 20-dimensional description of the urinary biochemistry for each rat. Principal components analysis and nonlinear mapping were used to reduce the biochemical parameter spaces for each rat to two or three dimensions for display and classification purposes. An investigation of alternative data presentation methods was made, and taking interanimal means of the map coordinates at each time point yielded a novel type of metabolic trajectory diagram with which the biochemical abnormalities associated with the HgCl2 and BEA lesions could be related to the progression and recovery phases of the toxic lesions. The time-course trajectories showed characteristically different paths for each toxin. These trajectories allowed the time points at which there were maximum metabolic differences to be determined and provided the visualization of net movements of the treatment group populations in time in relation to interanimal variation. Control animal urine samples subjected to this analysis showed simple clustering, with no evidence of metabolic trajectory. The trajectory for BEA showed different routes for onset of and recovery from toxicity, whereas for HgCl2 the outward trajectory (onset) mapped a space similar to the inward trajectory (recovery phase). This suggests that the NMR-detectable biochemical abnormalities after mercury toxicity mainly reflect the proportions of functional cells lining the nephron, whereas the biochemical abnormalities associated with renal medullary insult probably relate to functional integrity. An examination has been made for those metabolites that are most responsible for defining the trajectories, i.e., the discrimination of renal cortical and medullary toxicity from each other and from controls. These discriminatory metabolites (using paired t test, p < 0.001) included valine, taurine, trimethylamine N-oxide, and glucose for HgCl2 and acetate, methylamine, dimethylamine, lactate, and creatine for BEA, whereas citrate, succinate, N acetyl resonances from as yet unidentified metabolites, hippurate, alanine, and 2 oxoglutarate played an important role in defining the biochemically perturbed trajectory of both toxins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1435757 TI - Metabolite intermediate complexation of microsomal cytochrome P450 2C11 in male rat liver by nortriptyline. AB - Antidepressant drugs that contain alkylaminoalkyl substituents have been associated with serious pharmacokinetic interactions in humans that may be related to the inhibition of cytochrome P450 (P450) enzymes. In this study, the propensity of the tricyclic antidepressant nortriptyline (NOR) to inhibit individual microsomal P450 enzymes in rat liver was investigated to provide a mechanistic explanation for these pharmacokinetic interactions. Enzyme kinetic studies revealed that NOR inhibited steroid 2 alpha-, 6 beta, 7 alpha-, and 16 alpha-hydroxylation in untreated rat liver with Km/Ki ratios of 0.53, 0.59, 0.25, and 0.29, respectively. When the drug was preincubated with microsomes and NADPH before testosterone hydroxylation was conducted, marked increases in the Km/Ki ratios were observed (to 8.8, 3.9, 0.62, and 13, respectively). Thus, enzymic oxidation of NOR enhanced its inhibition capacity against P450 activities. Indeed, the altered Km/Ki ratios indicate 17-, 6.6-, 2.5-, and 47-fold increases in inhibition of the four pathways of testosterone hydroxylation after the biotransformation of NOR to its metabolites. From these experiments it was apparent that testosterone 2 alpha- and 16 alpha-hydroxylations, catalyzed predominantly by P450 2C11, were subject to the most pronounced increase in inhibition. Under these conditions, the apparent content of microsomal P450 was decreased, thus suggesting the formation of a NOR metabolite intermediate (MI) complex with the cytochrome. Further, optical difference spectroscopy of NADPH supported metabolism of NOR in microsomes and in a reconstituted system incorporating purified P450 2C11 indicated the appearance of an absorbance peak near 454 nm, similar to those produced by triacetyloleandomycin, SKF 525-A, and orphenadrine. Formation of this absorbance peak in microsomes was inhibited by an antibody raised against the male-specific P450 2C11. Because oxidative metabolism of NOR to inhibitory products would not necessarily involve MI complexation, additional experiments were undertaken in which NOR-related free metabolites produced in microsomal incubations were removed on Sep-Pak mini-C18 columns before estimation of testosterone hydroxylation. The principal finding from this experiment was that P450 3A2-dependent steroid 6 beta-hydroxylase activity was inhibited to a much lesser extent after removal of unbound NOR metabolites on Sep Pak columns (25% inhibition after Sep-Pak extraction, compared with 82% inhibition observed when all NOR metabolites were present during subsequent testosterone hydroxylation); inhibition of P450 2C11-mediated 2 alpha- and 16 alpha-hydroxylation was not noticeably different after Sep-Pak treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1435758 TI - Control analysis of rat liver glycolysis under different glucose concentrations. The substrate approach and the role of glucokinase. AB - Control Analysis has been carried out in the first steps of a rat liver glycolytic system. Attention has been focused on the effect of several glucose concentrations on the control, particularly regarding the role of glucokinase. From kinetic studies of the whole metabolic system we have obtained information on the flux variation under different glucose concentrations. This information together with the kinetics of glucokinase has allowed us to calculate Flux Control and Elasticity Coefficients for glucokinase and the Response Coefficient of the system with respect to glucose. The changes in of the value of Flux Control Coefficients demonstrates that in conditions of low glucose concentration, glucokinase is the main enzyme in controlling the flux through the pathway, but at high glucose concentration the control moves to phosphofructokinase. Next, we have compared our results with those obtained with the shortening and titration method, previously described (Torres, N.V., Mateo, F., Melendez-Hevia, E. and Kacser, H., (1986) Biochem. J. 234, 169-174; Torres, N.V. and Melendez-Hevia, E. 1991. Molec. Cell. Biochem. 101, 1-10). Furthermore, from knowledge of the enzyme kinetics of the system we have been able to build a model of the pathway that allows us computer similation of its behavior and calculation of the Flux Control Coefficient profile at different glucose concentrations. By the three methods the results correlate, supporting the use of the pathway substrate as external modulator of the metabolic system as a tool for practical application of Control Analysis. PMID- 1435760 TI - Release of anchored membrane enzymes by lipoamidase. AB - Lipoamidase is found to be able to release various membrane-anchored enzymes from the membrane compartment of pig brain. Released enzymes revealed their intact enzyme activities in the soluble fraction. Lipoamidase could release at least two types of anchored enzymes, i.e. glycosyl-phosphatidylinositol-bonded and myristoylated enzymes, but not integral membrane bound enzymes. The reaction was competitively inhibited by lipoyllysine. This releasing mechanism found in the membranes may play important roles in the secretory mechanism of extracellular enzymes and also in the cellular signal-transduction system through topological changes in cellular enzymes. PMID- 1435759 TI - The association of the human epsilon-globin gene with the nuclear matrix: a reconsideration. AB - The association of the human epsilon-globin gene with the nuclear matrix was studied in erythroid and non-erythroid cell lines. Using a high salt method to prepare histone depleted nuclei we studied the association of variety of fragments covering a 7.8 kb region which contains the human epsilon-globin gene. We furthermore studied the association of a set of DNA fragments covering the 13 kb human G gamma/A gamma-globin gene domain, the 16 kb psi beta/delta-globin gene domain and the 10 kb beta-globin gene domain with the nuclear matrix of K562 and Raji cells. The results show that all fragments studied are easily released from the nuclear matrix, indicating no specific association. Summarizing our results we could say that a region starting 5.7 kb 5' to the human epsilon-globin gene and ending 4 kb 3' to the human beta-globin gene seems to contain no attachment sites with the nuclear matrix of both erythroid and non-erythroid cells. PMID- 1435761 TI - Effect of spermine on peptide-bond formation, catalyzed by ribosomal peptidyltransferase. AB - The effect of spermine on the binding of AcPhe-tRNA to poly(U)-programmed ribosomes (step 1) and on the puromycin reaction (step 2) has been studied in a cell-free system, derived from E. coli. In the absence of ribosomal wash (FWR fraction) and at suboptimal concentration of Mg++ (6 mM), spermine stimulated the binding of AcPhe-tRNA at least five fold, while at 10 mM Mg++ there was a three fold stimulation. The above stimulatory effect was decreased at 6 mM Mg++, or was abolished at 10 mM Mg++ by the presence of FWR during the binding. Beside the stimulatory effect, spermine enhanced the stability of initiation complex AcPhe tRNA-poly(U)-ribosome. In step 2, spermine affected the final degree of puromycin reaction and the activity status of peptidyltransferase. Both stimulatory and inhibitory effects have been observed, depending on the experimental conditions followed during the binding of the donor and during the peptide bond formation. PMID- 1435762 TI - Transient elevation of aldose reductase mRNA in lens of rats developing galactose cataracts. AB - Aldose reductase (AR), a major enzyme in the polyol pathway, is thought to be responsible for accumulation of polyols in lenses exposed to high doses of galactose or glucose, and it may be linked to some of the complications found in diabetes. In this report we examined the level of expression of AR mRNA in lens epithelia undergoing development of galactose cataracts in vivo. The AR mRNA was quantitated by Northern blot hybridization with a [35S]-RNA transcript from a previously described AR cDNA clone. This was done on normal lens epithelia and on epithelia from lens of rats fed a diet of Purina Chow containing 50% galactose for periods of from 6 hr to 20 days. We found AR mRNA to elevate to about 5-fold the control levels by 12-24 hr on galactose, then decrease to the control levels by day 4. The increase in AR mRNA appears to be transitory. The high abundance in AR mRNA by 24 hr on galactose was confirmed by in situ hybridization. At later periods, from 8 to 20 days on galactose, a slow increase in AR mRNA took effect, as we have previously reported. Changes in the levels of galactose and dulcitol between 0 and 96 hr were also quantitated by gas chromatography, showing that there was a significant increase in both galactose and dulcitol occurring throughout the experimental period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435763 TI - Arachidonic and palmitic acid utilization in aged rat brain areas. AB - We have previously demonstrated that the arachidonic acid (20:4) incorporation into brain lipids differs according to the age of the animals used and the experimental conditions adopted. These differences led to a further investigation of arachidonic acid uptake in both aged and adult rat brains, its transformation into CoA derivatives, its incorporation into diacyl-glycerols and polar lipids, and finally its oxidation to CO2. These metabolic parameters were then compared with those obtained after using the saturated fatty acid palmitate (16:0). In both cases slices or mitochondria from different brain areas of 24-month-old and 4-month-old rats were examined. The results obtained indicate that the uptake of the fatty acids into cells is not modified by age. However, the successive metabolic transformations of the acids are altered to a considerable extent. In particular, in 24-month-old animals (compared with 4-month-old rats) there is a significant decrease of 20:4 in its incorporation into lipids as well as its oxidation to CO2, while arachidonoyl-CoA content increases by about 50%. This increased amount of CoA derivative, which has a potent detergent effect, may interfere with membrane structure and affect membrane physiological functions. Furthermore, because the free arachidonate pool is maintained in a dynamic equilibrium with its esterified forms, the final result may be a perturbation of this equilibrium. PMID- 1435764 TI - A kinetic description of sequential, reversible, Michaelis-Menten reactions: practical application of theory to metabolic pathways. AB - Equations are presented which describe a linear coupled system of reactions that utilize a single substrate and convert it to product by way of several intermediate enzyme catalysed steps. The present analysis extends previous results by assuming that the enzymes obey reversible Michaelis-Menten kinetics. In order for the system to reach steady state one must assume that the initial substrate concentration and the final product concentration are buffered to a constant value. Using the present analysis it can be shown that the system will not enter a steady state if the maximal velocity of any forward reaction is less than the steady state flux through the system. This condition represents a practical test for determining if a system will enter steady state but is valid only when the rate of the primary enzyme is not affected allosterically be intermediates in the pathway. The equations are used to analyse a portion of the rat liver glycogenic pathway that catalyses the conversion of glucose to fructose 1,6-bisphosphate. PMID- 1435765 TI - Detection of ischemia-reperfusion cardiac injury by cardiac muscle chemiluminescence. AB - Various methods have been used in the past to assess the implication of oxygen free radicals (OFR) in ischemia-reperfusion-induced cardiac injury. Luminol enhanced tert-butyl-initiated chemiluminescence in cardiac tissue reflects oxidative stress and is a very sensitive method. It was used to elucidate the role of OFR in cardiac injury due to ischemia and reperfusion. Studies were conducted on perfused isolated rabbit hearts in three groups (n = 8 in each): I, control; II, submitted to global ischemia for 30 min; III, submitted to ischemia for 30 min followed by reperfusion for 60 min. The heart tissue was then assayed for chemiluminescence (CL); content of malondialdehyde (MDA), an indicator of OFR induced cardiac injury; and activity of tissue levels of antioxidants [superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px)]. The control values for left and right ventricular CL and malondialdehyde were 81.1 +/- 15.4 (S.E.) and 182.4 +/- 50.3 (S.E.), mv.min.mg protein-1; and 0.024 +/- 0.006 (S.E.) and 0.324 +/- 0.005 (S.E.) nmoles.mg protein-1 respectively. Ischemia produced an increase in the cardiac CL (3.3 to 4.4 fold) and MDA content (2 to 2.6 fold). Reperfusion following ischemia also produced similar changes in CL and MDA content. The control values for activity of left ventricular SOD, catalase, and GSH-Px were 45.77 +/- 1.73 (S.E.) U.mg protein-1, 5.35 +/- 0.51 (S.E.) K.10( 3).sec-1.mg protein-1, and 77.50 +/- 7.70 (S.E.) nmoles NADPH.min-1.mg protein-1 respectively. Activities of SOD and catalase decreased during ischemia but were similar to control values in ischemic-reperfused hearts. The GSH-Px activity of left ventricle was unaffected by ischemia, and ischemia-reperfusion. GSH-Px activity of the right ventricle increased with ischemia, and ischemic reperfusion. These results indicate that cardiac tissue chemiluminescence would be a useful and sensitive tool for the detection of oxygen free radical-induced cardiac injury. PMID- 1435766 TI - Retardation of cell aging by lipid peroxidation. AB - Different concentrations of Fe2+/vitamin C mixtures were used as initiators of lipid peroxidation in diploid fibroblasts from cultured human embryonic lung. Malondialdehyde (MDA) formation in the cell cultures was correlated directly with the concentrations of Fe2+ and vitamin C. Lipid peroxidation was associated with an increase in life-span, decrease in the population doubling time and increase in cellular DNA synthesis. The effects of lipid peroxidation varied inversely with the MDA level. These data showed that low levels of lipid peroxidation retarded several biological properties of cultured cells that are associated with cell aging. PMID- 1435767 TI - Escherichia coli heat-labile enterotoxin preferentially interacts with blood group A-active glycolipids from pig intestinal mucosa and A- and B-active glycolipids from human red cells compared to H-active glycolipids. AB - The capacity of cholera toxin (CT) and of the heat-labile enterotoxin produced by Escherichia coli isolated from humans (LTh) to interact with glycolipids bearing ABO(H) blood group determinants isolated from different sources and separated by thin layer chromatography was studied. Toxin binding to the ABO(H)-related glycolipids depends on the glycolipid source, the type of the blood group activity, and the toxin. LTh and CT were capable of interacting with several blood group-active glycolipids from pig intestinal mucosa and both toxins preferentially recognize glycolipids isolated from animals carrying A-blood group antigenic determinants compared to those isolated from animals lacking these antigens. In contrast, LTh but not CT was able to interact with ABO(H)-active glycolipids from human erythrocytes. LTh preferentially binds to glycolipids isolated from A, B, and AB compared to O red cells. Results from competition experiments between CT and LTh for binding to the blood group-active glycolipids suggest that the carbohydrate structure requirements for the interaction of each toxin are different. The present findings may help to understand the results of clinical studies indicating an association between ABO(H) blood groups and the severity of diarrheal diseases produced by some toxigenic enterobacteria. PMID- 1435768 TI - Identification of calcium-dependent phospholipid-binding proteins (annexins) from guinea pig alveolar type II cells. AB - A new group of calcium-regulating proteins, called annexins or Ca(++)-dependent phospholipid-binding proteins (PLBP), have been detected in different species, organs and cell types. In the present study, we have identified and quantitated PLBP from guinea pig lung, lavage fluid and alveolar type II cells to elucidate the possible role of PLBP in lung surfactant biogenesis and secretion. Lungs were lavaged and type II cells from lavaged lung were isolated by elastase digestion and purified by centrifugal elutriation. For the quantitative identification of PLBP, we performed ELISA assays and Western blot analysis by using an antiserum raised in guinea pigs against a pure rabbit lung 36 kDa PLBP. The lavage fluid, cytosol from lung and type II cells contained 784, 167 and 435 ng per mg protein, respectively, of PLBP. The SDS-PAGE electrophoretic pattern and Western blot confirmed that all lung samples have band corresponding to a 36 kDa protein. This indicates that both alveolar type II cells and lavage fluid have higher levels of PLBP than whole lung cytosol. PMID- 1435770 TI - [Modified nucleosides and nucleotides inhibiting HIV replication: analysis of the situation and potential prospects]. AB - The results of an eight year search of blockaders of human immunodeficiency virus (HIV) among groups of modified nucleosides and nucleotides are reviewed. The molecular mechanism of action of these compounds is based on the inhibition of DNA polymerases activity. Attempts of systematic analysis of structure--anti-HIV activity relationship for modified substrates of DNA biosynthesis are made. In this analysis attention is focused on the evaluation of general properties of enzymes of the phosphorylation cascade and DNA polymerases. Such properties are analyzed on the basis of empiric rules which summarize electronic, steric and conformational properties of substrate analogs. The ability of phosphorylating nucleosides to block HIV reproduction are analyzed. The interdependence of structure of several most known inhibitors with their action on nucleic acids components metabolism as well as the structure--therapeutic properties relationship are discussed. PMID- 1435771 TI - [Spatial organization and conformational mobility of DNA complexed with nucleoproteins]. AB - The importance of spatial organization of DNA for the regulation of genome activity is discussed. The main problem reviewed in this paper includes cooperative interactions of proteins with DNA, formation of DNA loops in the regulatory domains of the genome and conformational mobility of DNA in chromatin. PMID- 1435769 TI - Vanadate-induced gene expression in mouse C127 cells: roles of oxygen derived active species. AB - An underinvestigated aspect of the mitogenic and cell regulatory actions of vanadium is the regulation of gene expression. Among the fifteen cellular genes studied in cultured mouse C127 cells, vanadium (as 10 microM sodium vanadate) increased levels of mRNA of the actin and c-Ha-ras to four times control values. These increases represented de novo synthesis of mRNA, since they were inhibited by actinomycin D. Vanadate did not increase mRNA corresponding to c-src, c-mos, c myc, p53, HSP70, pODC or RB genes, and expression of c-erb A, c-erb B, c-sis and c-fes genes was undetectable whether vanadium was present or not. Expression of a third gene affected by vanadium, c-jun, was augmented by addition of a reductant or oxidant together with the vanadate. Addition of NADH (marginally effective on its own) or H2O2 (effective alone) dramatically enhanced the effect of vanadate on c-jun gene expression. Catalase inhibited the effect of NADH partly. The vanadate-stimulated expression of actin and c-Ha-ras mRNA were unaffected by oxidants, reductants, metal chelators, or anti-oxidant enzymes. Evidently vanadate acts by two separate mechanisms on these two categories of genes. The alternate hypothesis that the actions of vanadate on actin and c-Ha-ras were mediated by a protein kinase cascade was inconsistent with the following observations. Neither insulin nor epidermal growth factor increased mRNA levels of c-Ha-ras or actin gene. Neither genistein (a tyrosine kinase inhibitor) nor pretreatment with 12-O-tetradecanoylphorbol-13-acetate blocked the actions of vanadate on these genes. Clearly the biological actions of vanadium depend in part on altered expression of genes. Since two of the genes are proto-oncogenes, this mechanism is potentially relevant to the mitogenic responses of cells to vanadium. PMID- 1435772 TI - [Expression of orthopoxvirus DNA sequences in Escherichia coli cells]. AB - We observed the expression of recombinant plasmids genes containing ectromelia virus DNA fragments in E. coli minicells. Using plasmids with vaccinia or ectromelia viruses DNA fragments inserted upstream of lacZ gene we showed that certain orthopoxvirus genome fragments carry out a promoter-like function in bacterial cells. PMID- 1435773 TI - [Coding part of the son gene small transcript contains four areas of complete tandem repeats]. AB - Overlapping cDNA clones for the smaller son gene transcript were isolated by several steps of human placenta cDNA library walking. Here we report the structure of repeats that exist at the long open reading, present in the structure of this smaller (5.6 kb) transcript of human gene son. We were able to identify in this transcript four areas of complete tandem repeats, formed by several steps of duplication. For three of them the extent of homology between amino acid sequences of repeated elements is higher than between their nucleic acid sequences. It means that amino acid sequences of repeated elements are conserved, that could reflect the structural significance for the function of hypothetical protein product of human gene son. On the basis of the results of analysis we proposed the model for the formation of repeats by processes of duplication, mutation and natural selection pressure at the expressed protein level. PMID- 1435774 TI - [The human son gene: the large and small transcripts contains various 5'-terminal sequences]. AB - Human son gene was previously identified by cloning and hybridization to GC-rich rat genomic fragment. After several cycles of human placenta library walking we were able to identify and clone two alternative transcripts of this gene. Recently we have determined nucleotide sequence of small son gene transcript, coding region of which contains four areas of complete tandem repeats. Here we report the structure of the part (2.9 kb) of large transcript of son gene from close to its 5'-end to the end of sequence, unique for this transcript. Comparison of nucleotide sequences of two transcripts indicates that they have common 3'-ends and, probably, arise from alternative splicing. 5' proximal part of large transcript contains two areas of complete tandem repeats not present in small transcript. Results of analysis of this area support our model for forming son gene tandem repeats structure by duplication, mutation and natural selection at the protein level. PMID- 1435775 TI - [Affinity modification of 80S ribosomes from human placenta with mRNA analogs- derivatives of oligouridylates with alkylating groups at the 3'-end]. AB - 2',3'-O-[4-(N-2-chloroethyl-N-methylamino)]benzylidene derivatives of oligoribonucleotides (Up)5U[32P]pC and (Up)11U[32P]pC were used for affinity labeling of 80S ribosomes from human placenta in the presence of cognate Phe tRNA(Phe). The derivatives retained the ability of tRNA(Phe)-dependent binding with 80S ribosomes and within the corresponding complexes were cross-linked to 40S subunits (preferentially to 18S rRNA). Sites of the mRNA analogs attachment were identified by blot-hybridization of the modified rRNA with restriction fragments of corresponding rDNA. They are located within positions 1610-1747 and 1748-1865 for both analogs. These fragments are situated at the 3'-end region of 18S rRNA in a highly conserved part of eukaryotic small subunit rRNA secondary structure. PMID- 1435776 TI - [Crystals of free aspartate aminotransferase]. AB - The crystals of free cytosolic chicken aspartate aminotransferase were subjected to X-ray investigation at 2.7 A. One subunit of the dimeric molecule crystalline enzyme is in the open conformation and the other is in the closed conformation. PMID- 1435777 TI - [Conformational stimulation in DNA type macromolecules]. AB - A concept for the description of structural elements mobility of a DNA-type macromolecule is suggested. The possible existence of conformational excitations weakly sensitive to a macromolecule heterogeneity in DNA is shown. The dependence of the macromolecule low-energy excitation spectrum on the nucleotide content is found and its sensitivity to thermal action is predicted. PMID- 1435778 TI - [Localization of conserved and variable segments in amino acid sequences of homologous proteins using a personal computer]. AB - A set of aligned homologous protein sequences is divided into two groups consisting of the most related sequences m and k. The value of the position variability of homologous protein sequences is defined as a number of failures to coincide in the intergroup comparison of all possible k x m pairs of amino acid residues in that position divided by k x m. The position variability value plotted vs the sequence position number with a window of 10 positions gives the intergroup local variability profile. The area S of the figure included between the local variability profile and the straight line corresponding to the mean local variability value is compared with the average area S(r) for 1000 random homologous protein families. If S is greater than S(r) by more than 2 standard deviation units sigma r the local variability profile is assumed to contain peaks and hollows corresponding to significant variable and conservative regions of the sequences. The profile extrema containing the area surplus delta S = S-(S(r) + 2 sigma r) are cut off by two straight lines to locate significant regions. The numerical experiment on the family of homologous phospholipases A2 revealed the linear dependence of the values S(r) and sigma r upon the position variability standard deviation sigma v of the homologous sequences. Furthermore, it was shown for protein families of various length (rhodopsins, aspartate aminotransferases, cytochromes b, L- and M-subunits of photosynthetic bacteria photoreaction centre and alpha-subunits of Na, K-ATPase), that delta S = S - n(S'r + 2 sigma r), where S - the area of the local variability profile, n = L/l (L - the length of the given protein family and l - the length of the hypothetical protein domain). If l = 250 then S'r = -1.42 + 62.56 sigma v and sigma'r = -0.14 + 7.46 sigma v. PMID- 1435779 TI - [Molecular cloning of the gene for secreted beta-galactosidase of the filamentous fungus Penicillium canescens]. AB - A secreted beta-galactosidase gene from P. canescens was cloned using synthetic oligonucleotide probes and its nucleotide sequence was partially determined. The gene was shown to be present in the genome as a single copy. The deduced primary structure of the signal peptide and the first 25 amino acid residues of the mature protein was established. The structure analysis of the beta-galactosidase gene revealed at least one short intron 64 bp long. The transcription start point was found to be located 89 bp upstream the initiation codon. Some peculiarities of the signal peptide cleavage mechanism are discussed. PMID- 1435780 TI - [Design of hybrid metalloproteinases from Bacillus]. AB - Possibility of using recombination mechanisms for the construction of hybrids between relative proteins containing highly homologous regions has been demonstrated. In order to design hybrid neutral proteases (NPr) NPr B. amyloliquefaciens--NPr B. brevis genes encoding these enzymes have been cloned into the same plasmid in tandem orientation with subsequent recombination between them. With the help of sequential inactivation we have managed to ensure efficient selection at intermediate stages as well as at the completion stage of construction when the desirable hybrid forms exhibited proteolytic activity. Constructions containing expressed genes of the hybrid neutral proteases NPr B. amyloliquefaciens--NPr B. brevis were obtained. The presence of several regions of high homology between the genes of the two Bacilli neutral proteinases determines the possibility of obtaining of various variants of hybrid proteins with different properties. PMID- 1435781 TI - [Interaction of mRNA of the p53 protein gene with ribosomal RNA]. AB - By blot hybridization we found that DNA fragments of eukaryotic 18 and 28S rRNAs bind specifically with mRNA. In these experiments the in vitro transcribed mRNA of mouse gene p53 was used. In addition we found that both 18 and 28S rRNAs were able to form intermolecular complexes with mRNAs of several genes 18S rRNA-mRNA; 28S rRNA-mRNA, but fail to bind the antisense RNAs of the same genes. The experimental data allow to suppose that 18S and 28S rRNAs carry several fragments that are complementary to some fragments in the mRNA sequences. PMID- 1435782 TI - [Theoretical analysis of the amino acid sequence of receptors for growth hormones and prolactins. Prediction of ligand-binding segments]. AB - At present the growth hormone and prolactin receptors were cloned along with their variant forms from human, rat, mouse, rabbit, bovine and sheep tissues. The functional topography of receptors is practically unknown. Because of the high price and difficulty of protein's total mutagenesis, it is reasonable to carry on a theoretical analysis of structures of receptors to predict the most probable ligand-binding sites. We studied the primary structures of known prolactin and growth hormone receptors using theoretical methods proved to be powerful in earlier structure--activity relationship investigations. We analyzed the secondary structure, conservative positions, hydrophilicity profiles of the growth hormone and prolactin receptors, and used the original method based on information theory to predict the sites which are promising for mutagenesis or peptide synthesis as probable ligand-binding sites. Three segments corresponding to the main conservative, hydrophilic and rare sites were predicted to form the ligand-binding determinant. PMID- 1435783 TI - [Comparison of the state of the area between B- and Z-segments of superhelical plasmids in vitro and in situ]. AB - The structure of B-Z junction in a cloned plasmid pGC20 containing a (dG-dC)10 insert at the SmaI site has been studied in vitro and in situ by modifying the DNA with O-beta-diethylaminoethylhydroxylamine (OHA). The latter is an analog of hydroxylamine possessing specificity with respect to unpaired cytidine. Experiments in vitro showed a complicated pattern of inhibiting the restriction hydrolysis of the OHA-modified DNA within the polylinker region of the plasmid. As the duration of the DNA reaction with OHA grows, a gradual increase in the inhibition of restriction is observed at the BamHI site neighboring the Z-insert and at the HindIII site at a distance of about 30 bp from the insert, while an intact segment (containing the SalGI site) is retained in the intermediate region. On passing to the cell level, only the region immediately adjacent to the Z-insert appears to be modified. According to estimates, about 30 to 40% of pGC20 molecules have the (dG-dC)10 insert in the Z-form when modified in situ in 1M OHA, pH 5.0. PMID- 1435784 TI - [Regulation of the expression of the c-fos gene in cells, reverting from being transformed to the pseudonormal phenotype]. AB - Regulation of c-fos expression in mice sarcoma cell lines CBA and C3H was investigated. Each of the cell lines was represented by a pair of clones: the tumorigenic and the one, which was produced from it by cloning. It was found, that c-fos expression in cells of the pseudonormal phenotype was similar to that in the normal fibroblasts. Experiments with cells reverted to pseudonormal phenotype transfected transiently or permanently with an indicator plasmid fos cat have shown, that a 600 bp sequence of the c-fos promotor including the TATA site, provides the expression level of the chloramphenicol acetyltransferase, correlating with the level of the c-fos mRNA expression. In the tumorigenic cells, permanent high activity of the cat gene expression was observed which was comparable to that in the normal fibroblasts stimulated by the embrionic serum or TPA. Activity of the transcription factors interacting with regulatory elements SRE, DSE, TRE did not correlate with the c-fos expression level in all the cells. PMID- 1435785 TI - [Study of transcription of the human cytochrome P450IID6 gene by polymerase chain reaction]. AB - Polymerase chain reaction was used to study the expression of the drug metabolism gene. Primers complementary to the 2070-2090 and 2912-2930 sites within exons 4 and 6 of the gene CYP2D6 were synthesized. The amplification of the cDNA from total human liver mRNA was achieved. The length of the fragment obtained (238 bp) was in accordance with the distance between the primers binding sites in cDNA. The amplification of the DNA from the same source led to the longer fragment due to the presence of introns. The total RNA from the blood cells of the extensive metabolizers was shown to contain the mRNA transcribed from the CYP2D6 gene. The Taq polymerase reaction in the presence of cDNA derived from a poor metabolizer did not lead to the synthesis of the 238 bp fragment. PMID- 1435786 TI - [Affinity modification of the 40S subparticle from human placenta with derivatives of pAUG and pAUGU3]. AB - Affinity labeling of 40S subunits from human placenta with 4-(N-2-chloroethyl-N methylamino)benzylmethyl-[32P]phosphoamide s of oligoribonucleotides pAUG and pAUGU3 was studied. Covalent attachment of these derivatives to 40S subunits within the complexes with 40S subunits, formed in the presence of Met-tRNAf.eIF 2.GTP, was detected. Both rRNA and ribosomal proteins were modified. Fragments of 18S rRNA, containing sites of the reagent attachment were identified: 1058-1164 for pAUG derivative and 976-1057--for pAUG and pAUGU3 ones. The data obtained allowed to conclude that the presence of the neighbouring codon at the A-site, regardless of the presence of the tRNA in it, affects significantly the arrangement of the trinucleotide template in the codon-anticodon interaction region. The large subunit does not cause significant alterations in the structural organization of the codon-anticodon interaction region. PMID- 1435787 TI - Alanine-scanning mutagenesis of human prolactin: importance of the 58-74 region for bioactivity. AB - We have generated 10 alanine mutants of human PRL (hPRL), a member of the PRL/GH family, to investigate the involvement of the highly conserved 58-74 region in the biological behavior of the protein. When treated with polyclonal anti-hPRL antibodies, all mutants were immunologically indistinguishable from the unmodified hPRL, and circular dichroism analyses indicated that their alpha-helix content was similar to that of the unmodified hormone. Mutations C58A, K69A, and, to a lesser extent, P66A affected drastically the ability of hPRL first to bind to the lactogenic receptor and second to stimulate the proliferation of Nb2 lymphoma cells, proving the importance of the 58-74 peptide segment for hPRL bioactivity. Binding affinities of these mutants to the Nb2 lactogenic receptor have been compared to lactogenic binding data previously obtained for several mutants of hGH. The comparison reveals that the residues involved in the biological properties of the two proteins are not at topologically equivalent positions. Hence, we suggest that the binding of these hormones to the lactogenic receptors occurs through a different molecular mechanism having distinct requirements at the residue level. PMID- 1435788 TI - Prohormone convertase-1 will process prorelaxin, a member of the insulin family of hormones. AB - Relaxin is a polypeptide hormone involved in remodeling of the birth canal during parturition. It is synthesized as a preprohormone precursor, which undergoes specific processing to form the mature two-chain disulfide-linked active species that is secreted by the cell. A major part of this processing requires endoproteolytic cleavage at specific pairs of basic amino acid residues, an event necessary for the maturation of a variety of important biologically active proteins, such as insulin and nerve growth factor. Human type 2 preprorelaxin was coexpressed in human kidney 293 cells with the candidate prohormone convertase processing enzymes mPC1 or mPC2, both cloned from the mouse pituitary tumor AtT 20 cell line, or with the yeast kex2 alpha-mating factor-converting enzyme from Saccharomyces cerevisiae. Prorelaxin expressed alone in 293 cells was secreted into the culture medium unprocessed. Transient coexpression with mPC1 or kex2, but not with mPC2, resulted in the secretion of a low mol wt species with an electrophoretic mobility very similar, if not identical, to that of authentic mature relaxin purified from human placenta. This species was precipitable by monoclonal antibodies specific for relaxin and had a retention time on reverse phase HPLC comparable to that of relaxin. Its analysis by both electrospray and fast atom bombardment mass spectrometry generated mass data that were consistent only with mature relaxin. The basic residues required for mPC1-dependent cleavage of prorelaxin are defined by site-directed mutagenesis. PMID- 1435789 TI - Modulation of glucocorticoid receptor function by protein kinase A. AB - Protein kinase A (PKA) has been shown to modulate the pattern of gene expression via transcription factors such as cAMP response element binding protein. However, in F9 embryonal carcinoma cells which lack endogenous functional cAMP response element binding protein, we have found that PKA is still able to control gene transcription through the glucocorticoid receptor (GR) by up-regulating its hormone-dependent trans-activation. Dose-response analysis indicates that PKA does not alter the ligand binding affinity of GR. PKA seems to act through the DNA binding domain of GR, since GR mutants which lack either the amino-terminal or the ligand binding domain are still able to be up-regulated by PKA. In support of this proposal, we demonstrate that PKA can enhance the DNA binding activity of GR. Our results suggest a novel mechanism by which PKA modulates the steroid sensitivity of a target cell by enhancing the DNA binding activity of GR for its cognate hormone response elements. PMID- 1435790 TI - Positive and negative thyroid hormone response elements are composed of strong and weak half-sites 10 nucleotides in length. AB - The steroid-thyroid hormone receptors bind to imperfect repeats of two or more half-sites. It is generally accepted that a T3 response element (TRE) half-site consists of a six-nucleotide core motif (5'-AGGT(C/A)A-3'). It is less widely appreciated that the nucleotides flanking this core motif also have a major influence on the affinity of T3 receptor (TR) for its response element. We analyzed TR-DNA interactions under conditions in which the affinity of receptor monomers for individual TRE half-sites of the rat GH (rGH) gene was measured. These studies avoided the effects of half-site spacing and orientation on receptor binding. Variations in the nucleotides flanking the core sequence can modulate receptor binding by more than 15-fold. Systematic mutational analysis of TRE half-site structure demonstrated that at least two nucleotides flanking either side of the half-site core motif strongly influence TR binding affinity and activity, indicating that half-sites are approximately 10 nucleotides long. Thus, the half-sites of most TREs overlap, and mutations in one half-site may affect the activity of its partner. The TRE half-site sequence 5'-CTGAGGTAACG-3' was bound with highest affinity by TRs. The negatively T3-responsive promoter of the rGH gene was used to investigate the functional significance of the nucleotides flanking the core motif in vivo. A promoter consisting of only 22 rGH nucleotides, containing two functional TRE half-sites which overlap the rGH TATA box, directed T3-inhibited transcription. Mutation of nucleotides flanking the core sequence of the weaker half-site dramatically reduced the activity of the element, demonstrating that the flanking sequences of the half-sites can profoundly affect TRE activity. PMID- 1435792 TI - [Milk feeding for healthy, mature infants]. PMID- 1435791 TI - Expression and regulation of a proenkephalin beta-galactosidase fusion gene in the reproductive system of transgenic mice. AB - A fusion gene containing 3 kilobases of human proenkephalin 5'-flanking sequences and 1 kilobase of human proenkephalin 3'-flanking sequence and the easily visualized histochemical marker, Escherichia coli beta-galactosidase, was used to study the function of cis-regulatory elements within the human proenkephalin gene in transgenic mice. Here data are presented on expression and regulation of this fusion gene in the reproductive system of three independent lines of transgenic mice. Within the male reproductive system, the fusion gene is expressed in the proximal epididymis and in developing germinal cells but not in mature or elongating spermatids. In the female reproductive system, the transgene was expressed at low basal levels, but expression was dramatically stimulated in the ovary and oviduct by hormonal stimulation and pregnancy; additionally, expression was induced at the uteroplacental junction in pregnant mice. Taken together these observations suggest that critical sequences for expression and regulation of the proenkephalin gene within the reproductive system are contained within sequences of the construct. PMID- 1435793 TI - [Human genetics and transplantation]. AB - Transplantations represent an important element of treatment in end-stage chronic disease both inborn (mostly genetic) and acquired (degenerative, neoplastic). They are supposed to establish durable coexistence of cells with different genetic origin (in most cases). This union is contradictory to immunological properties of the tissues involved and can only succeed in case of sufficient histocompatibility to be identified by the diagnostic tests of immunogenetics. This review discusses the current approach used in choosing the most appropriate donor for an individual patient, and in monitoring the maintenance of "chimerism" established by the transplantation focussing on bone marrow transplantation. Initially a general outline of indications for organ transplantation is given with emphasis laid on genetic disorders as the outlook of conservative treatments in inborn diseases is generally very poor. PMID- 1435794 TI - [Monoclonal hybrid antibodies. New perspectives for basic research and tumor therapy]. AB - Monoclonal hybrid antibodies are bi-specific constructs of two monoclonal antibodies with defined specificity. Hybrid antibodies can be used to force interactions between cell populations that under normal circumstances would not react with one another. Applications include the field of basic research as well as employment in therapy of malignancies and infectious diseases. The first part of this review describes the characteristic properties of hybrid antibodies and gives a short introduction into basic techniques for the production of these molecules. In the second part we present our observations on T-lymphocyte development studied with hybrid antibodies in fetal thymic organ cultures. Finally, we show that hybrid antibodies encompassing a binding site to the T-cell receptor and a binding site to a surface marker on tumor cells can be used to recruit cytotoxic T-cells to eliminate efficiently the malignant cells. Our data demonstrate that monoclonal hybrid antibodies are useful in the future development of new therapeutical principles, through facilitation of the immune response. PMID- 1435795 TI - [Pertussis--an illness with typical clinical symptoms?]. AB - There has been a noticeable increase in the incidence of pertussis in West Germany over the last decade. Since the availability of adequate bacteriological diagnosis a much broader clinical spectrum can be attributed to infections with B. pertussis. Three patients with an unusual clinical presentation of pertussis are presented. A three month old infant presented with severe apneic spells without cough as the sole clinical symptoms of the infection. B. pertussis was isolated in the nasopharyngeal swab. A nine month old premature infant with bronchopulmonary dysplasia after long time intubation and artificial ventilation presented with apneic spells, pulmonary and cardiac decompensation and required ventilatory support. The diagnosis was suggested by a massive leucocytosis with lymphocytosis. The diagnosis on the patient was established by serologic methods. Adult contacts of this patient developed longstanding cough and clinical signs of pertussis. The diagnosis of pertussis in these persons was established by nasopharyngeal culture. The third patient with trisomy 21 and a corrected AV canal suffered from nonspecific cough and gradually developed signs of congestive heart failure with pneumonia. B. pertussis was isolated from the nasopharynx. This patient showed neither the typical paroxysmal coughing spells nor disclosed the typical lymphocytosis in his white blood count. Microbiological investigations of patients with symptoms of respiratory tract infections should include the isolation of B. pertussis. Thus, additional cases of pertussis not suspected on the basis of their initial clinical presentation will be detected. PMID- 1435796 TI - [Embolism of the aortic bifurcation. Complication of bacterial endocarditis in childhood]. AB - Acute occlusion of the aortic bifurcation by a sattle embolus, as a complication of infective Endocarditis, is a very rare, extremely serious event. The treatment of choice consist in an immediate simultaneous bilateral femoral embolectomy. The indication for operation must be realised without delay based on anamnesis and physical examination. PMID- 1435797 TI - [Hepatitis B virus DNA. Detection with polymerase chain reaction in liver tissue of children with chronic hepatitis B]. AB - BACKGROUND: Detection of hepatitis B virus DNA is a reliable evidence of the presence of the viral agent and its replication. Conventional hybridization techniques are limited to detect about 30,000 virions. With the polymerase chain reaction it became possible to extend the sensitivity by amplification of viral sequences. In our study we intended to test whether viral sequences could be found in liver tissue specimens negative for hepatitis B virus DNA by conventional hybridization techniques. METHODS: Hepatitis B virus DNA was detected by PCR in liver tissue of 37 children with chronic hepatitis B, negative for hepatitis B virus DNA by Southern blot hybridization. PCR was performed in a thermal cycler using Taq-polymerase and oligonucleotide primers within the hepatitis B core region. Hepatitis B virus DNA was visualized by ethidium bromide staining and subsequent Southern blot hybridization. RESULTS: 20 patients were HBeAg- and 17 anti-HBe-seropositive. Viral sequences were present in each of the 20 HBeAg positive HBsAg carriers and in 10 patients with anti-HBe. No hepatitis B virus DNA could be found in 7 children, all of them positive for anti-HBe. CONCLUSIONS: Our results confirm polymerase chain reaction to be a more sensitive method to detect hepatitis B virus DNA in the liver compared with conventional hybridization techniques. Every HBeAg positive carrier as well as the majority of anti-HBe positive patients present viral DNA in their liver. Polymerase chain reaction will be suitable to monitor viral replication in spontaneous course and treated patients. PMID- 1435798 TI - [Effects of passive smoking on the pediatric respiratory tract]. AB - OBJECTIVE: To explore the risk of parental smoking to the respiratory health of their children data of a cross sectional study on fourth-grade schoolchildren in Munich and Southern Bavaria were analysed. METHODS: Allergic and asthmatic diseases and symptoms, risk factors like family history, indoor pollution and parental smoking were evaluated by a questionnaire. Pulmonary function tests were performed in 7284 school children aged (9-11 years). Lung function values were adjusted for height, weight, sex and other confounders. RESULTS: The children, whose parents smoke at home, had significantly lower levels of peak flow, MEF75, MEF50 and MEF25 compared to children from non-smoking families, with a dose response relationship. Smoking of more than 20 cigarettes at home is associated with a mean decrease in MEF75 of 5.7%, in MEF50 of 4.9% and in Peak Flow of 4.9% (p < 0.001). The prevalence of cough and wheezing increased with increasing smoking rates of the parents. CONCLUSIONS: Passive exposure to smoke has direct measurable dose-dependent effects on the respiratory system of children. PMID- 1435799 TI - [Does breast feeding prevent asthma and allergies? Results of the Munich asthma and allergy study]. AB - The relationship of breast feeding to atopic diseases is studied in a population based cross sectional study in Munich and Bavaria 1989/1990 in 6,535 german ten year old children. According to the questionnaire answers 1914 (29.3%) children were not breast fed, 2,368 (36.2%) shorter than 2 months, 1,744 (26.7%) 2 to 6 months and 509 (7.8%) more than 6 months. Compared to controls without any allergic disease the relative risk of later asthma, hayfever, atopic dermatitis and of allergic skin sensitization was not diminished by breast feeding. The same result pertained to high risk subgroups defined by positive family history of asthma or hayfever. It is concluded that breast feeding alone has no long term protective effect against atopic diseases. PMID- 1435800 TI - [Chronic hepatitis B. Treatment in childhood with alpha-interferon]. AB - BACKGROUND: In adults several trials of successful therapy for chronic hepatitis B using alpha-interferon with rates of seroconversion from HBeAg to anti-HBe of 30-40% have been reported. Despite the experiences in children are limited, alpha interferon seems to be a promising drug in this age group as well. We report on our results in the treatment of chronic hepatitis B virus carrier using the recombination interferon alpha-2b. METHODS: 24 children aged 0.6-16 years with chronic active or chronic persistent hepatitis B were included in the study. 12 children received 9 million units of alpha-interferon/m2 body surface area three times a week during four months. 12 control patients were not treated. The follow up period was 9-12 months after the beginning of therapy. HBsAg, anti-HBs, anti HBe and Hepatitis-B-Virus-DNA were assessed during this time on a regular basis. RESULTS: Only seroconversion of HBe-Ag to anti-HBe was considered as response to interferon treatment. During the follow-up period anti-HBe could be detected in 5 (41.6%) of the treated and in one (8.3%) of the untreated children. In one case additional seroconversion of HBsAg to anti-HBs due to virus elimination was observed. In all children a marked reduction of viral replication could be shown. 9 patients cleared Hepatitis-B-Virus-DNA at least for one time during therapy. Alpha-interferon was well tolerated and no severe side effects were observed. CONCLUSION: Our results demonstrate that alpha-interferon can be successfully applied to a considerable number of children with chronic hepatitis B. In patients responding to alpha-interferon usually serum transaminases become normal and infectivity of the disease is markedly reduced. alpha-Interferon treatment should be primarily recommended for children with chronic active inflammation. PMID- 1435801 TI - [Unnecessary public health measures in asymptomatic Salmonella carriers]. PMID- 1435802 TI - [Diagnosis of lung function in general practice]. PMID- 1435803 TI - [Idiopathic epilepsy with generalized seizures in early childhood]. AB - Idiopathic epilepsies with generalized seizures of early childhood are based on a genetic predisposition. The onset takes place between the first and fifth years of age, boys are affected more often than girls. Dependent on the clinical symptomatology you have to distinguish: myoclonic seizures; atonic-astatic seizures; myoclonic-astatic seizures; absences; tonic-clonic seizures. In more than half of the cases a combination of these seizures can be observed. The differentiation of epilepsies with generalized seizures of multifocal origin (infantile spasms, Lennox-Gastaut syndrome and Pseudo-Lennox syndrome [atypical benign epilepsy]) may be difficult but is essential. Therapy of choice is valproate, often in combination with ethosuximide (in children with minor seizures) or with kaliumbromide or phenobarbital (in children with tonic-clonic seizures). Generally the prognosis is more unfavourable if epilepsy starts in the first year of life with afebrile and febrile generalized tonic-clonic or clonic seizures, if children are suffering from longlasting states of seizures and if development is disturbed before beginning of epilepsy. PMID- 1435804 TI - [Transient, prolonged, combined sicca syndrome of the eyes and mouth. Occurrence along with a common cold in an 8-year-old girl]. AB - A girl of eight years fell ill with signs of common cold and bronchitis. Already on the second day of illness, before any treatment was started, she showed symptoms of a sicca-syndrome, beginning in the eyes, later the mouth. Ophthalmologic examination showed keratitis filiformis, histology of the salivary glands in the mucosa of the mouth was normal. Local substitution therapy led to subjective improvement. The disorder of secretion persisted for four months only, then rapid restitutio ad integrum of tears and saliva production occurred. Pathogenetically a parainfectious immunologic mechanism seems probable. During the observed period there were significant changes of antibody titers against RS virus and streptococci, but it is not possible to identify the cause of the illness really. We conclude that a sicca-syndrome with normal histology of mouth mucosa-glands is not necessarily prognostically infavorable. PMID- 1435805 TI - [Percutaneous Silastic catheters in newborn and premature infants. A report of experiences with 497 catheters in 5 years]. AB - BACKGROUND AND METHODS: Central catheters are an important prerequisite for adequate parenteral nutrition in preterm infants. However, a variety of complications have been shown to be associated with central lines: septicemica, thrombotic complications, mechanical complications. In this retrospective analysis we summarize our recent experience with central silastic catheters. RESULTS: Within a five-year-period (1986-1990). 497 silastic-catheters were inserted in 366 high risk neonates (mean birthweight 1360 g; 1060-1740 g, 25.-75. percentile) treated at the NICU, Department of Pediatrics, University of Gottingen. 451 catheters which were placed in a central position, were removed after an average duration of 11 days (mean; 8-18 days, 25.-75. percentile). During the observation period, 62.8 percent of the catheters were purposely removed. Making use of the Kaplan-Meier-curve, we calculated how long the catheter could stay without complications; 50% of all catheters could be expected to be in place for 25 days. The incidence of septicemia was 1.9%, bacterial contamination of the catheters was evident in 22% of all central lines. The most predominant microorganisms responsible for catheter-contamination were coagulase negative staphylococci. In addition, catheters were removed because of signs of phlebitis or suspected thrombotic complications (11.1%), and mechanical complications (dislocation, occlusion; 11.7%). Due to malposition of the central catheter two preterm infants developed pericardial effusions. There was no correlation between the site where the catheter was inserted and these complications. CONCLUSION: Central silastic catheters wherever clinically indicated are a valuable adjunct in the parenteral nutrition on high risk neonates. PMID- 1435806 TI - [In vivo studies of residual allergen activity of hydrolysate feeding]. AB - The capacity of food proteins to induce IgE-mediated reactions can be reduced by hydrolysis, heat treatment or ultrafiltration. It was the aim of our study to investigate the capacity of hydrolysates used for dietary purposes in cow's milk allergy to induce allergic symptoms in cow's milk sensitive children. Six different hydrolysates were tested by skin prick test and oral provocation test in 17 cow's milk sensitive children. Our data indicate that certain hydrolysates induce positive skin reactions as well as allergic symptoms after oral challenge. Casein hydrolysates were found to have the least residual allergenic activity. From our data we conclude that hydrolysates should be tested by titrated oral challenges before used in the diet of cow's milk sensitive children. PMID- 1435807 TI - [Intrapulmonary pressure measurements in high frequency ventilation of extremely small premature infants. The triggered airway occlusion method]. AB - The interrupter technique is an established method for measuring the intrapulmonary pressure in mechanically ventilated patients. We have developed a computer controlled method enabling us to interrupt the respiratory flow at precisely reproducible occlusion times (triggered by the respirator). It is therefore possible to determine the intrapulmonary pressure course in inspiration and expiration and the time constant for the upper respiratory tract (including the intratracheal tube) even in high-frequency ventilation. In 16 premature infants (mean birth weight 741 +/- 138 g, gestational age 26.1 +/- 1.9 weeks) we measured time constants between 58 and 190 msec for the intrapulmonary pressure decrease in expiration. An inadvertent PEEP between 1 and 4.5 cmH2O was found in 6 out of 23 examinations (ventilation frequency between 67 and 150/min, expiration times between 250 and 500 msec). The relation of expiration time to time constant was less than 4 in these cases only. The triggered interrupter technique is a useful, noninvasive method for monitoring the intrapulmonary pressure in neonates without disturbing the patient. Particularly in critically ill infants the measurements are the basis for optimal respirator settings. PMID- 1435808 TI - [Children with psychiatric disorders examined by established pediatricians]. AB - OBJECTIVE: Studies concerning children with psychological disorders presented in the paediatric practice are rare. We therefore investigated rates of attendance and rates of referral to other specialists from theses practices. METHOD: The data were collected by the paediatricians and recorded according to a list of psychosocial symptoms. Frequencies were compared with results of a similar study concerning general practitioners. The chi-square seemed to be appropriate as test of significance. RESULTS: 18 paediatricians were included in the study. 8.3% of children seen by these professionals were thought to show signs of psychological deviance. The accompanying physical disorders hereby were the more prominent presenting symptoms. Only in 1.3% of the cases were psychological disorders the sole reason for the visit. In 30% of the cases were psychological problems a follow up referral to another institution was recommended. Rates of attendance and of follow-up referral were more frequent in rural practices than in practices of a university town. In general practices, 20.3% of children were noted as psychologically disturbed. CONCLUSIONS: The study reveals the important role played by paediatric practices in the mental health care, especially in rural regions. The low rate of psychological disorders as the only reason for attending a paediatric practice indicates that there may be an attendance pattern in which physical symptoms are initially used as a vehicle for subsequently presenting psychological disturbance. PMID- 1435809 TI - [Epigastric colic after ceftriaxone therapy]. AB - The following article describes a girl with right upper quadrant abdominal colic following Ceftriaxon therapy for purulent meningitis. Ultrasound made it possible to demonstrate sludge-balls, floating in the gallbladder, a follow up examination was normal. Moreover the features of gallbladder precipitations following Ceftriaxon therapy will be described, and the clinical consequences will be discussed. PMID- 1435810 TI - [Has post-streptococcal glomerulonephritis disappeared?]. AB - We report on 21 children with poststreptococcal glomerulonephritis (PSGN). The diagnosis was based on clinical and laboratory criteria. 19/21 had a clinically apparent throat infection initially, but only 6 received antibiotic treatment. Initial symptoms were: macrohematuria (20/21), edema (10/21), arterial hypertension (6/21), reduced creatinine-clearance (11/21), and proteinuria (18/21). No Patient was dialyzed. After an interval of 0.3 to 25 months 19 children are asymptomatic. All patients have normal creatinine-clearances; none is hypertensive. The present data show that PSGN has not disappeared in Mid Europe. Remarkable acute disturbances occurred, which healed in almost all cases. The importance of accurate bacteriologic diagnosis and adequate therapy is emphasized. PMID- 1435811 TI - [Bacterial urinary tract infections]. PMID- 1435812 TI - [Grand mal epilepsy in childhood]. AB - Generalized tonic-clonic seizures are the most common type of convulsive disorders in children. They are always a sign of an epileptogenic cerebral dysfunction and present either acutely, predominantly as a single event with detectable origin, or chronically, recurring as an epileptic syndrome. In view of the etiology and classification of convulsions it is important to differentiate between primarily and secondarily generalized seizures. This distinction is first of all based on an exact description of the very beginning and of the course of the seizures, on the EEG findings and on any connection between the seizures and a particular time of day. Primarily generalized tonic-clonic seizures with and without associated petit mal seizures are manifestations of an idiopathic epilepsy and are most probably genetically determined, secondarily generalized seizures on the other hand are often signs of a central nervous lesion or of another symptomatic form of epilepsy. Benign idiopathic partial seizures, however, take the from of secondarily generalized convulsions during the morning sleep. Prolonged tonic-clonic seizures of any origin require vigorous treatment with anticonvulsants, if necessary in an intensive care unit. Recurrent seizures are treated with long-term anticonvulsant medication. The first-line treatment is valproic acid or phenobarbitone (or if necessary, a bromide) in primarily generalized seizures and carbamazepine or phenytoin in secondarily generalized convulsions. The recommended duration of this therapy and the risk of recurrence of seizures vary widely with the underlying etiology and the type of epilepsy. PMID- 1435813 TI - [Post-traumatic epilepsy]. AB - There might be 3 different forms of epilepsy following head injury: earliest seizures with occasional characteristics, early seizures prompting considerations of differential diagnosis, and, late seizures which might have a chronic course = posttraumatic epilepsy proper. The risks to have posttraumatic epilepsy for a child suffering from head injury are: penetrating cranial trauma, early seizures, intracranial hemorrhage, unconsciousness > 24 hours, depressed fracture with dural laceration and unconsciousness > 24 hours, fractures on the base of the skull, focal synchronous activity in the EEG which is related to the site of brain injury. If a or > or = 2 of b-g are given we recommend prophylactic antiepileptic therapy: in the younger (< 5 years) with a low dose of phenobarbital and in the elder (> 5 years) carbamazepine for at least 2 years of treatment. PMID- 1435814 TI - [Rupture of a renal artery aneurysm. Fulminant course, fatal complication of type IV Ehlers-Danlos syndrome in childhood]. AB - A 12 year old girl with joint laxity, hyperelastic and vulnerable skin and tall stature was labeled as "Marfan syndrome". She died unexpectedly from a ruptured aneurysm of the right renal artery. All these features are typical for Ehlers Danlos syndrome type IV. The diagnostic difficulties and the classification of connective tissue disorders are discussed and further possible complications are reviewed from the literature. The importance of an exact diagnosis is stressed in order to assess the prognosis and start possible therapeutic measures as early as possible. PMID- 1435815 TI - [Experiences with surfactant therapy of adult respiratory distress syndrome]. AB - We report on 2 patients with ARDS, who underwent a therapy with surfactant. In both cases the underlying reason for the lung disease probably was a viral pneumonia. In both patients the gas exchange improved after tracheal instillation of surfactant. This improvement however was much less than we know it from therapy of the respiratory distress syndrome of the premature babies. Reasons for these differences in response to surfactant are discussed. PMID- 1435816 TI - [Candida infections in premature infants weighing less than 1,500 g. Mucocutaneous colonization and incidence of systemic infections]. AB - BACKGROUND: An increasing incidence of systemic candidiasis has been reported in low birth weight infants requiring intensive care. We have retrospectively analyzed mucocutaneous Candida-colonization and infection rate in 422 preterm infants with a birthweight < 1,500 g. METHODS: All infants were treated at the NICU, University of Gottingen, from 1/1985-5/1991. 359 neonates (85%) were on mechanical ventilation, no prophylactic antimycotic regimen was applied. Mucocutaneous swabs and cultures from various anatomic sites were regularly obtained from all infants. RESULTS: 37/422 preterm infants (8.8%) had mucocutaneous colonization with candida, none of our patients developed systemic candidiasis. In 7 mechanically ventilated patients (1.9%) Candida albicans or Candida tropicalis was repeatedly detected in the bronchial secretions; 1 patient who had invasive Candida-pneumonia was effectively treated with 5-Fluocytosin and Fluconazol. 4/352 (1.1%) central silastic catheters were colonized with Candida albicans; none of these patients required specific treatment. CONCLUSION: The low rate of mucocutaneous Candida-colonization and invasive infection found in our patients may be explained--at least in part--by epidemiological and obstetrical factor as well as by the procedures of the neonatal management. PMID- 1435817 TI - [IgA endomysium antibodies. Detection in children with celiac disease]. AB - BACKGROUND: Epidemiology of coeliac disease gives rise to the search for a non invasive, reliable screening test. METHODS: We looked for IgA anti-endomysial antibodies (IgA-EmA) in 103 sera of 90 children (age: 2 months-13.9 years) using an indirect immunofluorescence method on monkey oesophagus sections. In 44 patients, the diagnosis of coeliac disease was confirmed fulfilling new criteria of the European Society of Pediatric Gastroenterology and Nutrition. RESULTS: All 24 coeliac disease patients with an initial flat mucosa had IgA-EmA (sensitivity 100%). In 36% of coeliac disease patients adhering to a gluten-free diet we found IgA-EmA. None of 46 patients in whom coeliac disease had been excluded by jejunal biopsy had IgA-EmA (specificity 100%). The sera of 102 blood-donors were used as controls and showed a test specificity of 99%. In coeliac disease patients, the titer of IgA-EmA declined during gluten-free diet by 0.66 steps/month on average, and rose 1.76 steps/month during gluten challenge. CONCLUSIONS: These results confirm the diagnostic significance of IgA-EmA for patients with suspected coeliac disease and their value for monitoring treatment even in young children (below 2 years). PMID- 1435818 TI - [Experiences with triple antibiotic combination in neonatal infection]. AB - BACKGROUND: In-vitro and clinical efficacy of a combination therapy consisting of 3 antibiotic agents was to be assessed in neonatal septicemia. METHODS: From 1980 to 1987, 152 newborns with septicemia as proven by blood culture were treated with an initial antibiotic regimen consisting of azlocillin (150 mg/kg bw), cefotaxime (100 mg/kg bw), and tobramycin (5 mg/kg bw). RESULTS: According to the microbiologic testing, antimicrobic therapy was effective in each of the 152 organisms: 101/152 bacteria were susceptible to all 3 agents; resistance to 1 or 2 of the antibiotics was evident in 33/152 and in 18/152 organisms, respectively. Mortality due to septicemia was 7.2%. CONCLUSION: As no difference was observed in the frequency in which one of the three antibiotic substances was the only effective drug, each of the 3 agents seemed to be necessary for clinical effectiveness of this antibiotic combination. PMID- 1435819 TI - [Prenatal diagnosis and therapy of adrenogenital syndrome with 21-hydroxylase deficiency. Position of the Pediatric Endocrinology Study Group of the German Society of Pediatrics and the Section of Pediatric Endocrinology of the German Society of Endocrinology]. PMID- 1435820 TI - [Perinatal calcium metabolism. Physiology and pathophysiology]. AB - During pregnancy, calcium is continuously transferred directly from the maternal intestine to the fetal bone, a transfer that is mainly induced by the interrelated actions of the calcium-regulating hormones parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)2D) and calcitonin. It has recently been demonstrated in animals that PTH-related protein (PTHrP) is the fetal equivalent of PTH. Human PTHrP, originally described as a product of a human lung cancer cell line and implicated in the pathogenesis of humoral hypercalcemia of malignancy, is a protein with 141 amino acids, and it has biochemical actions similar to PTH. It is believed that fetal PTHrP is mainly derived from the placenta during early gestation and from the fetal parathyroid glands during further development and that this protein has the role of maintaining the maternal-fetal calcium gradient either alone or in concert with 1,25(OH)2D. With birth, the placental supply of calcium ceases abruptly, stimulating the increase of PTH and 1,25(OH)2D, which are the main regulators of postnatal calcium metabolism. Alterations in the placental calcium (and phosphate) gradient may be caused by maternal hypo- or hypercalcemia and placental insufficiency and may be followed by transient disorders of calcium metabolism in the newborn. Due to abrupt cessation of the calcium and phosphate supply after delivery at a time when mineral demands are the highest, preterm infants are especially prone to hypocalcemia and osteopathy. If bone disease of prematurity is to be prevented, the amounts of calcium and phosphate must be adequate, as demonstrated by laboratory tests, the most important being calcium and phosphate in urine and alkaline phosphatase activity in serum. PMID- 1435821 TI - [Calcium, phosphorus and vitamin D administration in infancy. Unsolved questions]. AB - In premature infants calcium and phosphate supplementation should be continued until the infants weigh more than 2000 g, because osteopenia of prematurity has been described after discontinuation of the supplements at body weights of < 1800 g. Premature infants generally receive substantially more vitamin D than their daily requirements (> 400 IU), but then are no studies on the side effects of high vitamin D intake (hypercalciuria?). The extremely high calzitriol concentrations in plasma of premature infants who receive Ca/P supplements indicate that maximal stimulation of Ca/P absorption is necessary and present supplementation could still be inadequate. The daily vitamin D requirements of term infants are between 100 and 400 IU and no supplements are necessary if the infants are fed vitamin-D-fortified formulas. The high prevalence of rickets in infants on macrobiotic or vegetarian diets indicates that those infants should receive calcium and vitamin D supplements. PMID- 1435822 TI - Mineral nutrition and bone mineralization in full-term infants. AB - Bone mineralization is an intricate and tightly regulated process. Calcium, magnesium and phosphorus are the main minerals and play a principal role in skeletal mineralization. The following conclusions can be derived from different clinical studies. The large differences in Ca/P ratio between different formulas and between formulas and human milk suggest that most healthy full-term infants can adjust to a wide range of Ca/P ratio in their diet. The differences in serum levels of mineral and of mineral-regulating hormones are rarely clinically significant and most probably reflect continued compensatory mechanisms activated in response to dietary differences to maintain these levels within clinically normal ranges. Thus in most cases, these compensatory mechanisms are sufficient to reverse both short-term and long-term consequences and to prevent clinical disease. In the case of neonatal tetany, the compensatory mechanisms are overwhelmed, resulting in clinical signs and disease. Vitamin D is known to play an essential role in bone mineralization. Our studies have shown significant differences in vitamin D status in breast-fed infants with and without vitamin D supplementation and in infants fed various "humanized" formulas, whether cow milk based or soy protein-based. The major variables affecting bone mineralization are Ca/P ratio and mineral-regulating hormones. However, factors such as season, geography (i.e. sun exposure), race and sex may have a significant long-term influence on bone mineralization and mineral metabolism. Some biological differences such as differences in serum vitamin D metabolite level may directly effect Ca/P absorption and retention and thus bone mineralization and growth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1435823 TI - [A new method for determining mineral content of bones using ultrasound]. AB - With conventional methods radiation exposure is relatively high, due to frequent examinations. For this reason an alternative method for measuring bone mineral content was sought. Like X-rays, sound waves are subject to an exponential law of attenuation. For this reason the attenuation coefficient of the sound waves was used to describe the sound-conducting medium. With the help of this transmission sonographic method thickness dependence and increase in attenuation were shown as a function of increasing calcium apatite concentration using a reference system and also femoral sections of varying thickness. Examination of the reflected portion indicated that for this type of measurement the reflection at the bone is negligible at least in the first approximation. In the case of bone specimens a linear dependence was demonstrated between half-value thickness and mineral content in the area of bone calcium concentrations of 50-300 mg/cm. For practical employment of the method, a number of patients were examined in whom bone-mineral content fluctuations were to be expected on the basis of their disease and therapy. As the examinations indicate, fluctuations in vivo can be detected with the help of this method. PMID- 1435824 TI - [The clinical relevance of phosphorus and calcium in infant nutrition]. AB - This paper is an introduction to the clinical part of the symposium and deals with the question of whether and under which circumstances the calcium and phosphorus content in baby formula can provoke pathological conditions. In a healthy baby, high or low mineral intake is efficiently compensated for by Ca-P homeostasis. Both nutritional calcium deficiency and calcium excess are the exception with modern baby feeding practices. However, P-deficiency states resulting in phosphopenic rickets might occur in premature babies and in children with familial hypophosphatemic rickets. These two conditions should be treated and prevented by an alimentary P-supplement. On the other hand, formula with a rich P-content might be a cause of the late form of neonatal hypocalcemia. Therefore, a relatively low-phosphate formula preparation, similar to human milk, is recommended for the first 2 weeks of life of full-term newborns, as well for infants with hyperphosphatemic renal failure. PMID- 1435825 TI - Why is the phosphorus content of human milk exceptionally low? AB - The phosphorus supply of children and adults is adequate, and usually in excess. Therefore, it is surprising that in breast-fed infants phosphorus intake is very low. This is very rare among mammals. In infants three pathophysiological mechanisms argue in favour of a low, but adequate phosphorus intake in the presence of a balanced ratio of calcium to phosphorus. A low intestinal phosphorus concentration is an essential condition of an acid pH of the faeces, inhibiting the growth of potentially pathogenic germs. Owing to the characteristic renal physiology of the newborn, a small metabolic phosphorus surplus results in a high serum phosphorus level, a well-known risk factor for several disorders, e.g. hypocalcaemic tetany. During infections, impairment of intestinal calcium but not of phosphorus absorption results in an increased phosphorus and renal net acid excretion. Considering the low renal capacity for acid excretion in newborns, a high intake of calcium and phosphorus is a risk factor for the development of metabolic acidosis. It is thought that all three pathophysiologic mechanisms were effective in the biochemical evolution of humans, selecting women with a low phosphorus milk and infants with a constant high intestinal absorption rate of phosphorus. PMID- 1435826 TI - [Phosphate concentration. Does reduction in infant formula feeding modify the micro-ecology of the intestine?]. AB - The potential influence of phosphates in formulas on intestinal microflora was studied in 25 infants, aged 8 days to 12 weeks. The babies were either fed an infant formula with the usual phosphate concentration (n = 10) or an infant formula with reduced phosphate and protein concentrations (n = 7). The microbiological findings were compared with those obtained from breastfed infants (n = 8). Low-phosphate concentrations did not correlate with a predominance of bifidobacteria or suppression of putrefactive bacteria in the feces. The fecal excretion of phosphates and fat was found to be significantly lower with mother's milk compared to formulas both rich and poor in phosphate. Protein synthesis and breakdown rates, as well as the net protein gain, did not have a significant correlation with protein intake. PMID- 1435827 TI - Evaluation of a low-phosphate cow's milk diet on growth and bone mineralization of full-term infants. AB - Growth, bone mineralization and intestinal absorption were studied in 16 infants fed low-phosphate cow's milk and compared with a group of 15 infants fed conventional cow's milk. In the low-phosphate-fed infants the intestinal calcium absorption was as high as in infants fed human milk, the main characteristics of growth and bone mineralization being similar to those of infants fed conventional cow's milk. Urinary calcium was elevated with a low cAMP excretion. The relative hypercalciuria might be the result of the amount absorbed in excess of that used for the bone accretion. PMID- 1435828 TI - Technical aspects of phosphorus reduction and mineral adaptation in infant formulae. AB - Adapted milk-based formulae are complex products which simulate the protein and mineral composition of breast milk. The desired casein-to-whey protein ratio (40:60) in these formulae could be obtained by mixing cow's milk and whey. Unfortunately, this would yield formulae with too high a mineral content and a very unfavourable Ca:P ratio. The adjustment of the mineral content and the Ca:P ratio is the most sophisticated step in manufacture of such formulae. For this purpose, whey is demineralized with ion-exchange resins, electrodialysis or a combination of both processes. The demineralized whey (DW) obtained must be standardized in minerals by the addition of well-selected salts. After the standardization, whey is pasteurized, concentrated and dried, to give finally, the demineralized and standardized whey powder (DWPS). Addition of this ingredient to whole milk or skim milk leads to the standard adapted milk-based formula. Partial replacement of milk in the standard formula by caseinate leads to a low-phosphate formula with a Ca/P ratio equivalent to that found in breast milk. Because DWPS is quantitatively the most important ingredient of adapted milk-based formulae, the second most important being cow's milk, the nutritional and processing quality of DWPS strongly affects the heat stability and the nutritional and final quality of such formulae. PMID- 1435829 TI - Calcium and phosphorus metabolism in full-term infants. AB - Appropriate intake of dietary calcium and phosphorus is essential for the maintenance of mineral homeostasis and support of adequate bone mineralization in growing infants. Disturbances of calcium homeostasis such as newborn hypocalcemia, have been shown to be secondary to high oral phosphate intake. The incidence of hypocalcemic tetany has changed from epidemic proportions in newborns, who were formerly fed evaporated cow's milk formula, to the present sporadic occurrence in newborns who are now fed humanized cow's milk formula, with a calcium concentration of about 50 mg/dl and a phosphorus concentration of about 35 mg/dl. Human milk, provided vitamin D intake is adequate, has been shown to maintain calcium-phosphorus homeostasis and support adequate bone mineralization at least in the first 6 months of life. After this, the phosphorus content of breast milk could limit mineral accretion in exclusively breast fed infants. The present concentration of calcium and phosphorus in the humanized cow's milk formulas support adequate mineral homeostasis and bone mineralization throughout the first year of life. As bone calcium content is proportional to calcium intake, feeding whole cow's milk from early infancy onward is associated with abnormal bone mineralization. The adequacy of bone mineralization in infants fed soy formula is still controversial. PMID- 1435830 TI - The interface of science and medicine. PMID- 1435831 TI - Cancer cures. Yesterday, today, and tomorrow. PMID- 1435832 TI - Protein kinase C: implications for cancer prevention and treatment. PMID- 1435833 TI - Enzymes of the thymidylate cycle as targets for chemotherapeutic agents: mechanisms of resistance. AB - This brief review should serve to indicate that it is possible to assess tumor sensitivity to antifolates using fresh human tissue in short-term culture. The assays described differ from general assays of tumor sensitivity, such as the clonogenic assay or assays that measure 3H-thymidine incorporation as an indicator of cell viability (32-34), in that the effect of a drug on a human specific target (dihydrofolate reductase) is measured. These specific assays also may prove to be extremely useful in the detection of acquired drug resistance and for new analog drug development. In a general sense, this type of assay may eventually also be useful for guiding and selecting treatment for individual patients with other drugs with known mechanisms of action. Knowledge of the basis of tumor resistance is essential to develop new approaches to treatment, such as the use of other folate analogs that may still be effective, and to devise ways in which to selectively inhibit tumor cell growth using new analogs (trimetrexate) and leucovorin. PMID- 1435834 TI - Impact of cytogenetics and molecular genetics on leukemia therapy. PMID- 1435835 TI - Consistent genetic abnormalities in human cancers as targets for selective therapies. PMID- 1435836 TI - Advances in treatment for Hodgkin's disease. PMID- 1435837 TI - The evolution of curative cancer therapy. PMID- 1435838 TI - The past--prelude to the future. PMID- 1435839 TI - Successful successive studies in leukemia and breast cancer. PMID- 1435840 TI - Tamoxifen and endometrial cancer. AB - Tamoxifen is a nonsteroidal antiestrogen employed frequently in the treatment of breast cancer. An association between this drug and endometrial neoplasia has been reported. We report on 11 postmenopausal women with breast cancer who developed endometrial cancer while undergoing tamoxifen therapy and recommend aggressive investigation of vaginal bleeding in all women being treated with this agent. PMID- 1435841 TI - N10-propargyl-5,8-dideazafolic acid (CB3717): inhibitory effects on human leukemia cell lines resistant to methotrexate or trimetrexate. AB - The inhibitory effects of N10-propargyl-5,8-dideazafolic acid (CB3717), a quinazoline antifolate and a potent thymidylate synthase inhibitor, were evaluated in human leukemia cell lines resistant to methotrexate (MTX) and trimetrexate (TMQ). MTX-resistant MOLT-3 cell lines, MOLT-3/MTX200 and MOLT 3/MTX10,000, were cross-resistant to CB3717; however, the degree of resistance was only tenfold for both cell lines, and increased dihydrofolate reductase activity in MOLT-3/MTX10,000 had little influence on the degree of CB3717 resistance. The MOLT-3 cell line made resistant to TMQ, MOLT-3/TMQ200, was as sensitive to CB3717 as the parent line. The cell growth inhibitory effect of CB3717 on MOLT-3 was reversed by the addition of thymidine. Leucovorin also partially reversed CB3717-induced growth inhibition. Cellular uptake of MTX and 5 methyl-tetrahydrofolate was hindered by the presence of a high concentration of CB3717, whereas TMQ uptake was not influenced by CB3717. CB3717 appears to enter the cells not only through reduced folate transport system, but by other route(s). CB3717 does not share the transport pathway with TMQ. Our observations that MTX-resistant cells with increased dihydrofolate reductase are not more resistant than cells without increased enzyme activity, and that TMQ-resistant cells are not cross-resistant to CB3717, may have clinical relevance. PMID- 1435842 TI - Peripancreatic lymph node gastrinoma in a patient with Zollinger-Ellison syndrome. AB - The case of a patient who had Zollinger-Ellison syndrome caused by a primary peripancreatic lymph node gastrinoma is presented. Accompanying diffuse pancreatic islet cell hyperplasia, a well-documented occurrence in hypergastrinemia, was present. A perforated esophageal ulcer in a Barrett's esophagus led to right-sided necrotizing pleuritis, septicemia, and death. The diffuse parathyroid hyperplasia also noted in the patient is thought to be secondary to chronic hypertensive renal failure rather than MEN-I syndrome. PMID- 1435843 TI - Treatment of a large high-grade neurofibrosarcoma with concomitant vinblastine, doxorubicin, and radiotherapy. AB - A patient with neurofibromatosis developed a large inoperable malignant schwannoma on the posterior neck. The tumor underwent complete local regression following combined-modality treatment with radiotherapy, vinblastine, and doxorubicin. Vinblastine may be effective in combined-modality therapy. PMID- 1435845 TI - Organization battles fetal alcohol syndrome. PMID- 1435844 TI - Serotonin antagonists: treatment of chemotherapy-induced emesis. PMID- 1435846 TI - What is the mechanism of action for lasers that are being used to treat gynecologic conditions? PMID- 1435847 TI - A double-blind trial of 1% ketoconazole shampoo versus placebo in the treatment of dandruff. AB - The efficacy of 1% ketoconazole shampoo in the treatment of dandruff was tested in a double-blind, placebo-controlled trial with 176 patients. The application of the shampoo twice weekly gave a good or excellent result in 74% of the patients treated with ketoconazole versus 20% of the patients treated with placebo after 2 weeks. After 4 weeks these results were 80% versus 23%. The shampoo was well tolerated. Only one patient in the ketoconazole group stopped treatment because of greasy hair. PMID- 1435848 TI - Mycological aspects of inhalative mould allergies. PMID- 1435849 TI - Fatal haemoptysis associated with invasive pulmonary aspergillosis treated with high-dose amphotericin B and granulocyte-macrophage colony-stimulating factor (GM CSF). AB - Opportunistic pulmonary infections are a leading cause of morbidity and mortality in patients with chemotherapeutically treated neoplasias. With increasingly aggressive cytotoxic regimens causing prolonged neutropenia, the risk of systemic mycoses and in particular of invasive pulmonary aspergillosis has increased. We review the case of a 10-year-old child suffering from relapsed lymphoblastic leukaemia and from high-dose amphotericin B-treated invasive pulmonary aspergillosis acquired during long-standing neutropenia in the initial phase of remission induction chemotherapy. The patient died in remission after GM-CSF induced bone marrow recovery and clinical and radiological improvement with stable plasmatic coagulation and normal thrombocyte count. Peracute massive pulmonary bleeding caused by the simultaneous arrosion of a greater pulmonary artery and a lobar bronchus by a liquefactive fungal focus was responsible. In patients with chemotherapeutically induced neutropenia and invasive aspergillosis, bone marrow recovery may lead to the liquefaction of pulmonary foci, and, in view of the well-known vasotropic nature of the infection, to a potentially lethal arrosion bleeding. With the emerging use of colony-stimulating factors for shortening and overcoming neutropenia, this so far rare complication may become of increasing importance. PMID- 1435850 TI - Histopathology of human vaginal candidosis. AB - Histological changes of vaginal and ectocervical mucosa in women of reproductive age suffering from vaginal candidosis are described. The epithelial surface is covered with adherent masses composed of desquamated and destroyed epithelial cells and leucocytes impregnated with proteinaceous fluid and penetrated by pseudomycelium. The outer epithelial layers are characterized by dystrophic and necrobiotic changes, desquamation, formation of fissures and small cavities. Pseudomycelium penetrates 4 to 6 superficial epithelial layers. The barrier between the invading pseudomycelium and the blood vessels of the lamina propria papillae in some sites is only 5 to 6 flattened epithelial cells thick. In the basal epithelial layer, increased mitotic activity is noted. Lamina propria contains lympho-plasmocytic infiltrates. The problems of pathogenesis and diagnosis of vaginal candidosis are discussed in connection with the present findings. PMID- 1435851 TI - A modified method for experimental candidosis in mice avoiding lethality. AB - A model is presented which selected one out of 150 Candida albicans strains for the evaluation of antifungal agents. The mice were inoculated with 6 x 10(5) CFU of strain 352 into the tail vein. The strain has a moderate phospholipase B (PLB) activity in vitro and was originally isolated from a stool sample from a patient in an intensive care unit. This infection leads to very little suffering in the infected animals during the 6-day observation period. Kidney counts at day 5 after infection can give a first indication for a possible fungistatic mechanism. Possible interesting drugs can then be evaluated by a second set of experiments using a longer observation time to investigate the compounds for fungicidal properties. The model suggests that screening for systemic antifungals by avoiding lethality of mice in the first place can be done. PMID- 1435852 TI - The lectin type of Candida albicans--an epidemiological marker relevant to pathogenesis. AB - Fifty Candida albicans strains isolated from the oral cavities of HIV-infected patients were typed with 14 different lectins by means of agglutination reactions. Sixteen different lectin types could be distinguished, the most frequent type representing 22% of strains. A change in the lectin type was found in about half of the Candida albicans strains representing control cultures from identical individuals. A simplified typing scheme based on three lectins seems to be almost as efficacious for epidemiological application. PMID- 1435853 TI - A selective technique for isolation of three species of Chrysosporium from soils. PMID- 1435854 TI - Eggshell precursor proteins of Fasciola hepatica, I. Structure and expression of vitelline protein B. AB - Antibody raised against the major eggshell protein of Fasciola hepatica (vitelline protein B, vpB) is employed to isolate cDNAs from an expression library and to localize the protein in whole worms. Two cDNAs corresponding to the protein are homologous through the N-terminal and C-terminal coding regions and widely divergent internally. No repeated regions are apparent and no significant sequence homology is seen with chorion proteins of other genera although the amino acid composition closely reflects that of other chorion proteins. Microheterogeneity observed in the vpB is due to the presence of multiple coding sequences, transcripts and a gradient of post-translational modification. Relative transcription of the vpB mRNA throughout the female reproductive tract is demonstrated. PMID- 1435855 TI - Eggshell precursor proteins of Fasciola hepatica, II. Microheterogeneity in vitelline protein B. AB - At least 3 structural protein precursors of the eggshell are synthesized and stockpiled in the extensive vitelline cells of the liver fluke Fasciola hepatica L. One of these, vitelline protein B, consists of a closely related family of proteins that owes its apparent electrophoretic heterogeneity to variations in the Tyr to DOPA conversion as well as to subtle variations in the primary sequence. The efficiency of the Tyr to DOPA conversion ranges from a maximum of about 90% to a minimum of 55% in the protein. Trypsin digestion in borate buffer at pH 8 was used to produce DOPA-peptides for sequencing. Notably, trypsin does not cleave Arg/Lys-DOPA sequences at borate concentrations greater than 0.15 M. Peptides with DOPA-containing sequences most frequently have flanking amino acids such as Lys, Ser, or Asp on the N-terminal side and Gly or Asp on the C-terminal side. All protein variants fall within a narrow molecular weight range (30-33 kDa), a pI range of 6.9 to 8.3, and the collective majority would appear to share a common N-terminal sequence up to residue 28. The results suggest some combination of the following: variations in post-translational hydroxylation, alternative post-transcriptional splicing and/or the existence of multiple gene copies of eggshell precursors. The latter have been shown to occur in the blood fluke Schistosoma mansoni [15]. PMID- 1435856 TI - Identification and purification of glucose phosphate isomerase of Plasmodium falciparum. AB - The multiplication of malaria parasites within red blood cells is energy dependent. Since these parasites lack a functional tricarboxylic acid cycle, the energy needs of the parasite are met by anaerobic glycolysis of exogenous glucose. High levels of glycolytic enzymes such as fructose-1,6-diphosphate aldolase, phosphoglycerate kinase and pyruvate kinase have been detected in infected erythrocytes. Here we report a 4-9 times increase in glucose phosphate isomerase (GPI) activity of infected erythrocytes over that of normal erythrocytes. This increase is of parasitic origin, as additional enzyme bands were observed in lysates of infected erythrocytes. The expression of GPI parallels parasite maturation and reaches a maximum at the trophozoite/schizont stage. Two distinct but closely related activity patterns consisting of 3-4 GPI isoenzymes (not shown in normal erythrocytes) with neutral to weakly acidic isoelectric points were observed in 6 P. falciparum isolates tested by isoelectric focusing. The purified P. falciparum GPI has an apparent size of 66 kDa. No size variation was observed in the 6 P. falciparum isolates studied. Furthermore, antiserum raised against this protein in BALB/c mice specifically inhibits parasite encoded GPI activity while no effect was observed on host enzyme activity. PMID- 1435857 TI - Genetic variants within the genus Echinococcus identified by mitochondrial DNA sequencing. AB - The pattern of species and strain variation within the genus Echinococcus is complex and controversial. In an attempt to characterise objectively the various species and strains, the sequence of a region of the mitochondrial cytochrome c oxidase subunit I (CO1) gene was determined for 56 Echinococcus isolates. Eleven different genotypes were detected, including 7 within Echinococcus granulosus, and these were used to categorise the isolates. The 4 generally accepted Echinococcus species were clearly distinguishable using this approach. In addition, the consensus view of the strain pattern within E. granulosus, based on a variety of criteria of differentiation, was broadly upheld. Very little variation was detected within Echinococcus multilocularis. Remarkable intra strain homogeneity was found at the DNA sequence level. This region of the rapidly evolving mitochondrial genome is useful as a marker of species and strain identity and as a preliminary indication of evolutionary divergence within the genus Echinococcus. PMID- 1435858 TI - Humoral immune response against a 70-kilodalton heat shock protein of Entamoeba histolytica in a group of patients with invasive amoebiasis. AB - In order to investigate the humoral immune response against Entamoeba histolytica a lambda ZapII cDNA library was constructed from trophozoites of the pathogenic E. histolytica strain SFL-3. The library was screened with serum IgG from a patient with invasive amoebiasis. Forty-nine immunopositive lambda clones were isolated and partial sequences from the inserts were obtained. By comparison of the sequences with the merged database MIPSX from the Martinsried Institute for Protein Sequences we were able to identify homologous proteins for 36 of the clones. Twenty-six of the clones encoded intracellular proteins, among these, the major part (16 clones) were highly homologous to the eukaryotic 70-kDa heat shock proteins (Hsps). The open reading frame of one complete clone encodes a protein of 656 amino acid residues of 71.5 kDa which has 69.8% sequence identity with the human Hsp70 protein. In a larger screening experiment only 3 out of 12 patients detected with their IgG the phage which expressed the 70-kDa heat shock protein(s). PMID- 1435859 TI - Characterization of carbohydrate metabolism and demonstration of glycosomes in a Phytomonas sp. isolated from Euphorbia characias. AB - Phytomonas sp. isolated from Euphorbia characias was adapted to SDM-79 medium. Cells isolated in the early stationary phase of growth were analyzed for their capacity to utilize plant carbohydrates for their energy requirements. The cellulose-degrading enzymes amylase, amylomaltase, invertase, carboxymethylcellulase, and the pectin-degrading enzymes polygalacturonase and oligo-D-galactosiduronate lyase were present in Phytomonas sp. and were all, except for amylomaltase, excreted into the external medium. Glucose, fructose and mannose served as the major energy substrates. Catabolism of carbohydrates occurred mainly via aerobic glycolysis according to the Embden-Meyerhof pathway, of which all the enzymes were detected. Likewise, the end-products of glycolysis, acetate and pyruvate, glycerol, succinate and ethanol were detected in the culture medium, as were the enzymes responsible for their production. Mitochondria were incapable of oxidizing succinate, 2-oxoglutarate, pyruvate, malate and proline, but had a high capacity to oxidize glycerol 3-phosphate. This oxidation was completely inhibited by salicylhydroxamic acid. No cytochromes could be detected either in intact mitochondria or in sub-mitochondrial particles. Mitochondrial respiration was not inhibited by antimycin, azide or cyanide. The glycolytic enzymes, from hexokinase to phosphoglycerate kinase, and the enzymes glycerol kinase, glycerol-3-phosphate dehydrogenase, phosphoenolpyruvate carboxykinase, malate dehydrogenase and adenylate kinase, were all associated with glycosomes that had a buoyant density of about 1.24 g cm 1 in sucrose. Cytochemical staining revealed the presence of catalase in these organelles. The cytosolic enzyme pyruvate kinase was activated by fructose 2,6 bisphosphate, typical of all other pyruvate kinases from Kinetoplastida. The energy metabolism of the plant parasite Phytomonas sp. isolated from E. characias resembled that of the bloodstream form of the mammalian parasite Trypanosoma brucei. PMID- 1435860 TI - Cloning and analysis of the RESA-2 gene: a DNA homologue of the ring-infected erythrocyte surface antigen gene of Plasmodium falciparum. AB - We have cloned and sequenced a homologue of the ring-infected erythrocyte surface antigen (RESA) gene from Plasmodium falciparum designated RESA-2. Two reading frames with high homology to exon 1 and exon 2 of RESA at both the nucleotide and amino acid levels were identified in the RESA-2 sequence. However, RESA-2 does not contain either of the blocks of tandem repeats present in RESA. The lack of an RNA transcript in either asexual or sexual stage parasites and the presence of an in-frame stop codon in the second reading frame suggests RESA-2 could be a pseudogene. Its lack of expression in asexual stages demonstrates that it does not complement the RESA deletion in isolate FCR3. PMID- 1435861 TI - The characterization of two monoclonal antibodies which react with high molecular weight antigens of asexual Plasmodium falciparum. AB - We prepared rat monoclonal antibodies (mAb) specific for very large Plasmodium falciparum proteins to assist in their characterization. Hybridomas prepared from rats immunized with parasitized erythrocyte (PE) proteins of greater than 200 kDa exhibited two patterns of Western blot reactivity with PE SDS extracts: one represented by clone 41E11 (IgM, kappa), the other by clone 12C11 (IgM, lambda). MAb 41E11 reacted by Western blotting with at least 15 antigens, most of which comigrated with antigens identified by the 33G2 human IgM mAb. The stage specificity of mAb 41E11 reactivity and indirect immunofluorescence (IFA) pattern closely resemble those previously described for antigens that share the EEXXEE sequence motif. Unlike mAb 33G2, MAb 41E11 immunoprecipitated a biosynthetically radiolabeled protein of 320 kDa. MAb 41E11 did not immunoprecipitate any cell surface 125I proteins. MAb 12C11 reacted on Western blotting with a different group of malarial antigens of approximately 44, 95, 117, 145, and 310 kDa, as well as with some low-molecular-weight, uninfected erythrocyte antigens. MAb 12C11 did not immunoprecipitate any cell surface 125I or biosynthetically labeled proteins. The 310-kDa antigen recognized by mAb 12C11 (denoted Ag 12A) does not correspond to PfEMP2 or the 320-kDa antigen recognized by mAbs 33G2 or 41E11. With trophozoites and more mature stages, fixed IFA reactivity of mAb 12C11 was at the parasite and in antigen aggregates in the host cell cytoplasm that extended to the PE plasma membrane. Indirect results suggest that Ag 12A does not correspond to cell surface-exposed PfEMP1 and is most likely a hitherto unidentified malarial protein. PMID- 1435862 TI - Cloning and characterization of a repetitive DNA sequence specific for Trichomonas vaginalis. AB - A family of 650-bp-long repeats from the Trichomonas vaginalis genome, designated the Tv-E650 family, was cloned and sequenced. The nucleotide sequence is A+T-rich (73.3% A+T in the consensus sequence) and highly conserved among the 8 molecular clones analyzed. The differences among the clones are single-nucleotide and 2 nucleotide substitutions and insertions or deletions. The sequence uniformity of the clones as well as the presence of identical mutations in different clones suggest that efficient sequence homogenization mechanisms, such as gene conversion or recurring unequal crossing-over, operate in T. vaginalis. The copy number of the Tv-E650 repeats was estimated to be about 10(2)-10(3) per genome. Based on the DNA hybridization results, the Tv-E650 repeat family is conserved in all T. vaginalis strains examined, regardless of their diverse geographical origin. No hybridization of the Tv-E650 probe was found with the DNA from Trichomonas tenax, Trichomonas gallinae and Pentatrichomonas hominis, indicating that the Tv-E650 repeated sequences are species-specific. A dot blot hybridization protocol was developed which does not require isolation of DNA. By using this protocol it was possible to detect the DNA released from approximately 10(3) T. vaginalis cells per dot. These observations suggest that the Tv-E650 probe is potentially applicable to the identification and detection of T. vaginalis. PMID- 1435863 TI - Invasion of hereditary ovalocytes by Plasmodium falciparum in vitro and its relation to intracellular ATP concentration. AB - Hereditary ovalocytes (stomatocytic ovalocytes), when examined within 1-2 days from the time that the blood sample is drawn, are invaded by Plasmodium falciparum in culture to the extent of at least 55% of normal control cells. The ovalocytes have extremely rigid membranes, characterised by a shear elastic modulus some 3-4 times greater than that of normal cells. The extent of invasion falls off very much more rapidly than that into normal cells on storage, and we surmise that this is the reason for earlier reports of resistance of ovalocytes to malarial invasion in vitro. The initial loss of susceptibility to invasion with time is not accompanied by any change in membrane rigidity, but is primarily a consequence of a rapid decline in intracellular ATP concentration: this falls to below the threshold level required for invasion (approx. 0.1 mM) over a period in which the ATP in normal cells remains almost constant. Incubation in a metabolic regenerating medium leads to a rise in the intracellular ATP concentration and invasion by P. falciparum is recovered, though to a much lower extent than in normal cells. The resistance of ovalocytes to invasion becomes irreversible, due possibly to degradative processes in the membrane, on further storage. The developing parasites in ovalocytes have a reduced number of merozoites and show distinct morphological abnormalities. PMID- 1435864 TI - Molecular analysis of the cytosolic and glycosomal glyceraldehyde-3-phosphate dehydrogenase in Leishmania mexicana. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity was detected in two cell compartments of Leishmania mexicana promastigotes. These activities could be attributed to two different isoenzymes, one residing in glycosomes, the other in the cytosol. We have cloned and sequenced the genes for both isoenzymes. The glycosomal enzyme is encoded by two tandemly linked genes of identical sequence and contains features frequently found in glycosomal enzymes: the presence of peptide insertions, a small carboxy-terminal extension with a potential glycosomal targeting signal (-SKM) and an excess of positively charged residues (net charge +7). Only one open reading frame was detected for the cytosolic enzyme. The amino acid sequences of the two proteins are only 55% identical. We discuss some evolutionary aspects of the observed organization of the GAPDH genes in the Trypanosomatidae and the role of the two isoenzymes in the metabolism of these organisms. The possibility to develop GAPDH-specific inhibitors that will be effective against the enzyme of various parasitic members of this family is explored. PMID- 1435865 TI - A procyclin-associated gene in Trypanosoma brucei encodes a polypeptide related to ESAG 6 and 7 proteins. AB - The procyclin genes of Trypanosoma brucei encode a family of glycoproteins expressed on the surface of procyclic forms of the parasite. These genes are present at different loci in tandem arrays of two or three copies depending on the strain. It has previously been shown that procyclin genes are transcribed from a promotor immediately upstream of the first procyclin gene in each cluster by an RNA polymerase that is resistant to high levels of alpha-amanitin. Here we show that additional genes, which we term procyclin-associated genes (PAGs), are located downstream of the procyclin genes and belong to the same alpha-amanitin resistant polycistronic transcription units. A gene in the pro A locus, PAG 1, encodes a polypeptide that is related to the ESAG 6 and 7 proteins encoded in the VSG expression site. An unexpected feature of PAG 1 is that the major open reading frame of 405 amino acids only starts at position 1283 in the cDNA sequence and extends to the poly(A) tail. Sequences related to the 5' untranslated region of PAG 1 are also found downstream of procyclin genes in other loci, but the 3' coding region is unique to Pro A. This suggests that there are related PAGs which are coordinately transcribed with procyclin genes from different loci. PMID- 1435866 TI - DNA fingerprinting of Trypanosoma cruzi: a new tool for characterization of strains and clones. AB - Using nonradioactive hybridization, the human multilocus probe 33.15 was shown to recognize multiple minisatellite regions in nuclear DNA from Trypanosoma cruzi, producing complex banding patterns on Southern blots, typical of DNA fingerprints. The DNA fingerprints were stable and were capable of identifying different strains of the parasite. Individual clones of the Y strain showed different banding patterns, demonstrating that the strain is heterogeneous. In general, the sensitivity and specificity of DNA fingerprinting was similar to that obtained with kinetoplast DNA restriction analysis. However, it has the advantages of being technically simple and of studying nuclear rather than mitochondrial DNA. Thus, it is a useful new tool for the characterization and study of strains and clones of Trypanosoma cruzi. PMID- 1435867 TI - Identification and expression of a Fasciola hepatica gene encoding a gut antigen protein bearing repetitive sequences. AB - A Fasciola hepatica cDNA clone of about 2 kb was isolated from an expression library by immunological screening using blood serum from an experimentally infected calf. The cDNA clone hybridised to a RNA of about 3 kb in a Northern blot experiment. The nucleotide sequence of the cDNA revealed the presence of an open reading frame of 1636 bp which encoded 24 tandemly arranged 20-amino acid long repeats, followed by 65 non-repeated residues preceding the stop codon. This antigen was expressed in Escherichia coli as beta-galactosidase fusion proteins which were used for the production of specific antibodies. Immunofluorescence studies using specific antifusion sera revealed that the antigen was specifically expressed in the parasite intestine epithelial cells. Due to its early appearance it might be possible to design diagnostic assays based on this repeated antigen for identification of recently infected animals. PMID- 1435868 TI - Hycanthone resistance in schistosomes correlates with the lack of an enzymatic activity which produces the covalent binding of hycanthone to parasite macromolecules. AB - Crude extracts of hycanthone sensitive Schistosoma mansoni incubated at 37 degrees C in the presence of ATP and Mg2+ induced the covalent binding of tritiated hycanthone (HC) to macromolecules. The same behavior was shown by the HC sensitive species, Schistosoma rodhaini, whereas two independently isolated HC resistant S. mansoni strains had no detectable activity. Sensitive male schistosomes had more activity than females or immature worms. Virtually no activity was present in mouse liver, in human liver, in HeLa cells or in the naturally resistant species Schistosoma japonicum. The activity was destroyed by boiling or by Proteinase K treatment. Covalent binding of tritiated HC to macromolecules could be inhibited by cold HC, oxamniquine or IA-4, while none of the in vitro ineffective analogs, like lucanthone, UK-3883 or 4-desmethyl lucanthone, were inhibitory. These results strongly support the previously advanced suggestion that HC is activated by enzymatic mechanisms which are present only in drug sensitive schistosomes. PMID- 1435869 TI - The actin genes of Onchocerca volvulus. AB - The genome of Onchocerca volvulus was found to contain 2 actin gene classes (called 1 and 2) of 2 genes each. The 4 genes are located in 2 clusters (called A and B), each containing a gene class member. Five short introns of 122-207 bp occur within each gene. The sequences of the fourth intron and the 5' and 3' untranslated regions of all the 2 gene classes are completely different even though their coding regions share 95% identity. Mature transcripts from the actin genes have the nematode spliced leader (SL) at their 5' ends. One actin cDNA was found to be derived from an actin pre-mRNA which locks both the 5 introns and the 5' SL, suggesting that in at least some transcripts cis-splicing is completed before trans-splicing occurs. PMID- 1435870 TI - The electrochemical proton gradient in the bloodstream form of Trypanosoma brucei is dependent on the temperature. AB - The membrane potential and pH gradient over the plasma membrane of the protozoan parasite Trypanosoma brucei were measured with radioactive indicators in combination with the silicone oil centrifugation technique over a range of temperatures. At 37 degrees C a small membrane potential and pH gradient of similar magnitude, but of opposite polarity, were measured. The resulting electrochemical proton gradient was almost zero. However, when the temperature was lowered from 37 degrees C to 22 degrees C, the internal pH was kept constant independent of the external pH and a membrane potential of between -100 and -150 mV was measured, depending on the external pH. Measurements at various temperatures between 15 degrees C and 37 degrees C revealed that above 26 degrees C the membrane potential collapsed and that this collapse correlated with a sudden increase in membrane fluidity. The uptake of 2-deoxy-D-glucose and of pyruvate, which are both mediated by facilitated diffusion carriers in the plasma membrane of the trypanosome, were also affected by this sudden increase in fluidity of the membrane. The overall rate of the conversion of glucose into its metabolites, which is independent of the plasma membrane, varied only gradually. We conclude (i) that major changes occur in the plasma membrane of T. brucei around 26 degrees C, that affect all membrane related processes; (ii) that the electrochemical proton gradient plays a minor role in the energy metabolism of T. brucei when it resides in the bloodstream of the mammalian host at 37 degrees C; and (iii) that below 26 degrees C an electrochemical proton gradient is maintained over the plasma membrane. PMID- 1435871 TI - Nucleotide sequence of a representative member of a Trypanosoma cruzi dispersed gene family. PMID- 1435872 TI - A Plasmodium falciparum gene coding for a 15-kilodalton antigen expressed in asexual stage parasites, gametocytes and gametes. PMID- 1435873 TI - Molecular cloning of cDNA and genomic sequences coding for the 35-kilodalton subunit of the galactose-inhibitable lectin of pathogenic Entamoeba histolytica. PMID- 1435874 TI - Cloning and characterisation of members of a family of Babesia bigemina antigen genes containing repeated sequences. AB - Bovine polyclonal antisera to Babesia bigemina antigens separated by phenyl Sepharose chromatography were used to screen a B. bigemina lambda gt11 cDNA expression library. Eleven B. bigemina-specific cDNA clones were studied in detail. DNA sequencing of 2 representative clones identified open reading frames encoding polypeptides representing the carboxy-termini of 2 different proteins. Both polypeptides contained a related central motif of tandem repeats flanked by a highly conserved carboxy-terminal region, but the sequences preceding the repeats were not related. Hybridisation and restriction enzyme analysis of the cDNA clones indicated that they were derived from a family of at least nine related, but not identical genes. Four different members of the gene family have been isolated from a B. bigemina lambda EMBL3 genomic library. The genes are not closely linked and they occur on the largest and smallest B. bigemina chromosomes resolved by pulsed field gel electrophoresis (PFGE). Antibodies raised against the native antigens and purified on recombinant fusion proteins bound to multiple proteins (50-70 kDa) in the original B. bigemina antigenic fractions. PMID- 1435875 TI - A multicopy, extrachromosomal DNA in Leishmania infantum contains two inverted repeats of the 27.5-kilobase LD1 sequence and encodes numerous transcripts. AB - Leishmania DNA 1 (LD1) is a 27.5-kb sequence that occurs as an inverted repeat in a 55-kb multicopy, circular DNA in Leishmania infantum ITMAP263. The sequence is also found with a different genomic organization, possibly a tandem array, within a 1.5-Mb chromosome in all Leishmania isolates. About 26 stable transcripts of LD1 sequence, ranging from 0.6 to 15 kb, are found in ITMAP263. Transcripts were detected from both strands of the entire LD1 sequence, but the inverted repeat nature of the circular molecule prevented determination of whether transcription proceeded in one or both directions. Nine abundant transcripts (0.6-8.4 kb) from adjacent regions on the same strand of the repeat unit may represent mature mRNAs. One of these transcripts was shown to contain the 39-nucleotide spliced leader sequence characteristic of the 5' termini of trypanosomatid mRNAs. Several transcripts from the other strand of the repeat unit are also abundant and contain sequence complementary to some of the putative mRNAs. Less abundant, larger transcripts that span sequences encoding abundant mRNAs are also present, suggesting that transcription of LD1 is polycistronic. PMID- 1435876 TI - Molecular characterization of two genes encoding members of the glucose transporter superfamily in the parasitic protozoan Leishmania donovani. AB - The polymerase chain reaction was used to clone two genes from Leishmania donovani, each of which encodes a member of a superfamily of membrane transporters which include the mammalian facilitative glucose transporters. One of these transporters, designated D2, is similar in sequence and overall structural features to a previously cloned Leishmania transporter Pro-1. Both D2 and Pro-1 are developmentally regulated genes which are expressed primarily in the insect stage of the parasite life cycle. In contrast, the second novel transporter, D1, is structurally quite different from either D2 or Pro-1, and its expression is not regulated during the parasite life cycle. All three genes are located on different chromosomes in L. donovani. PMID- 1435877 TI - Dynamics and size polymorphisms of minichromosomes in Leishmania major LV-561 cloned lines. AB - Various lines and cloned lines of Leishmania major of varying degrees of virulence in BALB/c mice possessed size polymorphic multicopy minichromosomes related to previously described LD1/CD1 and 715-class DNAs of Leishmania. The minichromosomes were not necessary for virulence. Two of these DNAs (M180 and M210), coexisting in a single cloned line, showed remarkable dynamics in terms of loss or gain when followed through multiple transfers during in vitro culture and in vivo passage in BALB/c mice. Although there was significant sequence heterogeneity among minichromosomes, M180 sequences were present within large (megabase) and in intermediate (550-760 kb) chromosomes in the L. major lines analysed. M180 related small DNAs were also detected in Leishmania mexicana and Leishmania donovani isolates, suggesting that the generation of these molecules involves a common, probably functional basic mechanism widespread in Leishmania. PMID- 1435878 TI - A transferrin-independent iron uptake activity in Plasmodium falciparum-infected and uninfected erythrocytes. AB - Non-heme iron is essential for the asexual growth of the human malaria parasite Plasmodium falciparum in mature erythrocytes. Utilization of iron bound to serum transferrin by the parasitized cells has been postulated, but direct evidence for its specific delivery has not been reported. Here we demonstrate that normal levels of transferrin in human serum are not required for intraerythrocytic P. falciparum growth: culture medium immunodepleted 500-1000 fold in human transferrin was capable of supporting parasitemias and rates of invasion comparable to those observed in non-depleted medium. 55Fe bound to transferrin was not taken up by infected cells. A transferrin-independent non-heme iron uptake activity was, however, detected in both infected and uninfected erythrocytes when iron was presented to the cells as 55Fe-NTA or 55Fe-citrate. Although the uptake activity was not parasite specific, the radiolabel was found in association with parasites mechanically released from the infected erythrocytes, indicating that it is delivered to the intracellular organism. Evidence is presented that the transferrin-independent iron uptake activity is time-, temperature- and concentration-dependent, but apparently not energy dependent. PMID- 1435879 TI - The translation initiation site of recombinant Trypanosoma brucei ornithine decarboxylase varies with different promoters. AB - Expression of the Trypanosoma brucei ornithine decarboxylase (ODC) gene in Escherichia coli behind the lambda phage PR promoter led to the production of a recombinant enzyme having the same subunit molecular weight as the native enzyme [4]. However, when the same gene is expressed behind the tac promoter or the phoA promoter, the ODCs produced by the transformed E. coli have subunit molecular weights approximately 2 kDa higher than that of the native enzyme. Amino terminal sequencing of the recombinant proteins indicates that the ODC synthesized under control of the lambda PR promoter actually starts at the second methionine (Met23) of the open reading frame, whereas those produced in the latter two cases begin at the first methionine (Met1). Analysis of the 5'-end of T. brucei ODC mRNA supports the conclusion that translation initiates at Met23. We postulate that, for the lambda PR promoter, translation initiates at Met23 instead of Met1 because of the formation of a stable secondary structure in the region of the Met1 and the presence of a good E. coli consensus translation initiation site upstream of Met23. We have constructed a new plasmid using the pho A promoter to express recombinant T. brucei ODC starting at Met23 in large quantities. PMID- 1435880 TI - Unilateral transplantation of human fetal mesencephalic tissue into the caudate nucleus of patients with Parkinson's disease. AB - BACKGROUND: Parkinson's disease is characterized by the loss of midbrain dopamine neurons that innervate the caudate and the putamen. Studies in animals suggest that fetal dopaminergic neurons can survive transplantation and restore neurologic function. This report compares the clinical results in four case patients with severe Parkinson's disease who underwent stereotaxic implantation of human fetal ventral mesencephalic tissue in one caudate nucleus with the results in a control group of similar subjects assigned at random to a one-year delay in surgery. METHODS: Each case patient received cryopreserved tissue from one fetal cadaver (gestational age, 7 to 11 weeks). Before implantation, adjacent midbrain tissue underwent microbiologic, biochemical, and viability testing. Cyclosporine was administered for six months postoperatively. RESULTS: The procedure was well tolerated. Three case patients showed bilateral improvement on motor tasks, as assessed on videotape, and were more functional in the activities of daily living, as assessed by themselves and neurologists, during both optimal drug therapy and "drug holiday" periods. One case patient, who died after four months from continued disease progression, had striatonigral degeneration at autopsy. In the patients who received transplants, optimal control was achieved with a lower dose of antiparkinsonian medications, whereas the controls required more medication. Positron-emission tomography with [18F]fluorodopa before and after surgery in one patient revealed a bilateral restoration of caudate dopamine synthesis to the range of normal controls, but continued bilateral deficits in the putamen. CONCLUSIONS: Although the case patients continued to be disabled by their disease, unilateral intracaudate grafts of fetal tissue containing dopamine diminished the symptoms and signs of parkinsonism during 18 months of evaluation. PMID- 1435881 TI - Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson's disease. AB - BACKGROUND AND METHODS: Patients with Parkinson's disease tend to have a reduced response to levodopa after 5 to 20 years of therapy, with "on-off" fluctuations consisting of dyskinesia alternating with immobility. In an effort to modify the motor disability of advanced Parkinson's disease, we implanted embryonic mesencephalic tissue containing dopamine cells into the caudate and putamen of seven patients. Two patients received unilateral grafts in the caudate and the putamen on the side opposite the side with worse symptoms. Five patients received bilateral grafts implanted in the putamen only. In six of the seven patients, the fetal tissue was obtained from a single embryo with a gestational age of seven to eight weeks. The tissue was injected by means of 10 to 14 needle passes. There were no surgical complications. Four of the seven patients underwent immunosuppression with cyclosporine and prednisone. RESULTS: All patients reported improvement according to the Activities of Daily Living Scale when in the on state 3 to 12 months after surgery (P < 0.01). Neurologic examination according to the Unified Disease Rating Scale showed that five of the seven patients improved when in the on state six months after surgery. The mean group Hoehn-Yahr score improved from 3.71 to 2.50 (P < 0.01). Computer and videotape testing in the home supported these findings. Fluctuations in clinical state were moderated, and periods of dyskinesia and off episodes were shorter and less severe than before implantation. Drug doses were reduced by an average of 39 percent (P < 0.01; maximum, 58 percent). The results of clinical evaluation and fluorodopa positron-emission tomography in one patient were compatible with transplant survival for as long as 46 months. Both immunosuppressed and nonimmunosuppressed patients improved. CONCLUSIONS: Fetal-tissue implants appear to offer long-term clinical benefit to some patients with advanced Parkinson's disease. PMID- 1435882 TI - Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) AB - BACKGROUND: Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism. METHODS: We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation. RESULTS: Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications. CONCLUSIONS: Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease. PMID- 1435884 TI - Brief report: atrial systolic failure in primary amyloidosis. PMID- 1435883 TI - A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group. AB - BACKGROUND: Mortality is very high in lactic acidosis, and there is no satisfactory treatment other than treatment of the underlying cause. Uncontrolled studies have suggested that dichloroacetate, which stimulates the oxidation of lactate to acetyl-coenzyme A and carbon dioxide, might reduce morbidity and improve survival among patients with this condition. METHODS: We conducted a placebo-controlled, randomized trial of intravenous sodium dichloroacetate therapy in 252 patients with lactic acidosis; 126 were assigned to receive dichloroacetate and 126 to receive placebo. The entry criteria included an arterial-blood lactate concentration of > or = 5.0 mmol per liter and either an arterial-blood pH of < or = 7.35 or a base deficit of > or = 6 mmol per liter. The mean (+/- SD) arterial-blood lactate concentrations before treatment were 11.6 +/- 7.0 mmol per liter in the dichloroacetate-treated patients and 10.4 +/- 5.5 mmol per liter in the placebo group, and the mean initial arterial-blood pH values were 7.24 +/- 0.12 and 7.24 +/- 0.13, respectively. Eighty-six percent of the patients required mechanical ventilation, and 74 percent required pressor agents, inotropic drugs, or both because of hypotension. RESULTS: The arterial blood lactate concentration decreased 20 percent or more in 83 (66 percent) of the 126 patients who received dichloroacetate and 45 (36 percent) of the 126 patients who received placebo (P = 0.001). The arterial-blood pH also increased more in the dichloroacetate-treated patients (P = 0.005). The absolute magnitude of the differences was small, however, and they were not associated with improvement in hemodynamics or survival. Only 12 percent of the dichloroacetate treated patients and 17 percent of the placebo patients survived to be discharged from the hospital. CONCLUSIONS: Dichloroacetate treatment of patients with severe lactic acidosis results in statistically significant but clinically unimportant changes in arterial-blood lactate concentrations and pH and fails to alter either hemodynamics or survival. PMID- 1435885 TI - Misoprostol for the treatment of peptic ulcer and antiinflammatory-drug-induced gastroduodenal ulceration. PMID- 1435886 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 47-1992. A 25-year-old man with chronic intermittent coccygeal pain and mild bladder dysfunction. PMID- 1435887 TI - Fetal-tissue transplants in Parkinson's disease. PMID- 1435888 TI - Are there really alternatives to the use of fetal tissue from elective abortions in transplantation research? PMID- 1435889 TI - Should healthy women take tamoxifen? PMID- 1435890 TI - Prediction of survival in lung cancer. PMID- 1435891 TI - Continued zidovudine or didanosine for human immunodeficiency virus infection. PMID- 1435892 TI - Continued zidovudine or didanosine for human immunodeficiency virus infection. PMID- 1435893 TI - Continued zidovudine or didanosine for human immunodeficiency virus infection. PMID- 1435894 TI - Case 22-1992--pathogenesis of cat scratch disease. PMID- 1435895 TI - A bovine albumin peptide as a possible trigger of diabetes mellitus. PMID- 1435896 TI - Health care in Canada. PMID- 1435897 TI - Health warnings, smoking, and cancer. The Cipollone case. PMID- 1435898 TI - Host-specific interleukin-2-secreting donor T-cell precursors as predictors of acute graft-versus-host disease in bone marrow transplantation between HLA identical siblings. AB - BACKGROUND: Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings. METHODS: We determined the frequency with which host-specific interleukin-2 secreting donor T-cell precursors occurred in 16 consecutive pairs of HLA identical siblings before they underwent marrow grafting. The results were correlated with the development of acute GVHD after transplantation. RESULTS: High frequencies of host-specific T-cell precursors (> or = 1 per 100,000) were detectable before transplantation in eight donors whose siblings later had severe (grade II or III) acute GVHD. Among the donors to eight patients with mild (grade 0 or 1) acute GVHD, low frequencies (< 1 per 100,000) were found. CONCLUSIONS: Analysis of the frequency of such cells before transplantation may be a useful predictor of severe acute GVHD in allogeneic bone marrow transplantation between HLA-identical siblings. It is possible that the patients at risk for serious acute GVHD after marrow grafting may benefit from some alternative form of immunosuppressive therapy. PMID- 1435899 TI - Isolation of Rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis. AB - BACKGROUND: Bacillary angiomatosis is characterized by vascular lesions, which occur usually in patients infected with the human immunodeficiency virus (HIV). A newly described gram-negative organism, Rochalimaea henselae, has been associated with cutaneous bacillary angiomatosis, but no organism has been isolated and cultivated directly from cutaneous tissue. METHODS: We used two methods to isolate the infecting bacterium from four HIV-infected patients with cutaneous lesions suggestive of bacillary angiomatosis: cultivation with eukaryotic tissue culture monolayers and direct plating of homogenized tissue onto agar. The patients' blood was cultured with the lysis-centrifugation method. Isolates recovered from skin and blood were identified by sequencing all or part of the 16S ribosomal RNA gene amplified with the polymerase chain reaction. RESULTS: R. quintana, historically known as the agent of trench fever, was isolated from cutaneous lesions in three patients, after tissue homogenates were cultivated with endothelial-cell monolayers; R. henselae was isolated from a cutaneous lesion in one patient. In two patients, R. quintana was isolated from both cutaneous tissue and blood; in one patient it was also isolated from bone. CONCLUSIONS: In bacillary angiomatosis, either of two species of rochalimaea--R. quintana or R. henselae--can be isolated from cutaneous lesions or blood, providing an additional method of diagnosis. PMID- 1435900 TI - A less costly regimen of alglucerase to treat Gaucher's disease. AB - BACKGROUND: Alglucerase (Ceredase) provides effective enzyme-replacement treatment for patients with Gaucher's disease, but at the usually recommended dose of 60 U per kilogram of body weight every two weeks (130 U per kilogram per month), it costs $382,200 per year for a 70-kg patient. Theoretical considerations suggest that more frequent administration would be more efficient. METHODS: Fourteen patients with type 1 Gaucher's disease that was moderately severe to severe were given 30 U of alglucerase per kilogram per month, in divided doses given either daily or three times weekly, or 120 U given three times weekly. The effect of the treatment on the size of the liver and spleen and on blood counts was compared with published data on patients who received a total dose four to five times as large as the lower dose we used and who received treatment every two weeks. RESULTS: The response to 30 U of alglucerase per kilogram per month, fractionated into three or seven doses weekly, was approximately the same as that reported after the administration every two weeks of a dose four or five times as large, given in the large infusions usually recommended. A fourfold increase in the dose given three times weekly, from 2.3 to 9.2 U per kilogram, did not substantially increase the rate of improvement. CONCLUSIONS: The treatment of Gaucher's disease with smaller total doses of alglucerase given more frequently yields satisfactory results. A dose of 2.3 U per kilogram three times weekly yields major financial benefits with no sacrifice of therapeutic effect. Even taking into account the increased ancillary costs of more frequent administration, this method of administering alglucerase reduces the annual cost of the drug for a 70-kg patient to about $100,000. PMID- 1435901 TI - Nonmelanoma cancers of the skin. PMID- 1435902 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 48-1992. An 82-year-old man with pulmonary densities and a mass in the left upper abdominal quadrant. PMID- 1435903 TI - No price too high? PMID- 1435904 TI - Problems with employer-provided health insurance--the Employee Retirement Income Security Act and health care reform. PMID- 1435905 TI - Pharmaceutical promotions. PMID- 1435906 TI - Pharmaceutical promotions. PMID- 1435907 TI - Pharmaceutical promotions. PMID- 1435908 TI - Pharmaceutical promotions. PMID- 1435909 TI - Pharmaceutical promotions. PMID- 1435910 TI - Pharmaceutical promotions. PMID- 1435911 TI - Pharmaceutical advertising in the Journal. PMID- 1435912 TI - Pharmaceutical advertising in the Journal. PMID- 1435913 TI - Abnormalities of the left temporal lobe in schizophrenia. PMID- 1435914 TI - Abnormalities of the left temporal lobe in schizophrenia. PMID- 1435915 TI - Intracoronary ultrasound imaging of graft thrombosis. PMID- 1435916 TI - A noninvasive method of predicting pulmonary-capillary wedge pressure. AB - BACKGROUND: The noninvasive prediction of pulmonary-capillary wedge pressure (PCWP) is important for the recognition and treatment of a variety of cardiovascular disorders. The response of the arterial pressure to the Valsalva maneuver has been shown to correlate with the PCWP. We therefore devised a noninvasive method to measure this pressure response at the bedside and correlated these measurements with the PCWP measured directly with a pulmonary artery catheter. METHODS: Simultaneous, blinded, noninvasive measurements of the ratio of the final amplitude to the initial amplitude of the pulse wave form during the stress phase of the Valsalva maneuver (pulse-amplitude ratio) and direct measurements of the PCWP were obtained in 20 clinically stable patients and in 14 clinically unstable patients who were receiving vasoactive agents, 12 of whom also had endotracheal tubes in place. RESULTS: Using linear regression analysis, we found that the pulse-amplitude ratio strongly correlated with the measured PCWP over a range of base-line values from 4 to 32 mm Hg for the 20 clinically stable patients (R2 = 0.80) and the 14 clinically unstable patients (R2 = 0.85). The method also correctly predicted changes in the PCWP after the administration of nitroglycerin or furosemide and after expansion of the intravascular volume (R2 = 0.79). CONCLUSIONS: These preliminary data indicate that a simple noninvasive method can accurately predict the PCWP and changes in the PCWP in response to medical therapy. PMID- 1435918 TI - Images in clinical medicine. Acute bacterial endocarditis. PMID- 1435917 TI - Brief report: complete deficiency of plasminogen-activator inhibitor type 1 due to a frame-shift mutation. PMID- 1435919 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 49-1992. A 70-year-old man with multisystem failure after a sextuple coronary-artery-bypass graft procedure. PMID- 1435920 TI - Breast cancer. PMID- 1435921 TI - Breast cancer. PMID- 1435922 TI - Breast cancer. PMID- 1435923 TI - Treatment of preterm labor with the beta-adrenergic agonist ritodrine. PMID- 1435924 TI - Treatment of preterm labor with the beta-adrenergic agonist ritodrine. PMID- 1435925 TI - Treatment of preterm labor with the beta-adrenergic agonist ritodrine. PMID- 1435926 TI - Treatment of preterm labor with the beta-adrenergic agonist ritodrine. PMID- 1435927 TI - The prognostic value of serum troponin T in unstable angina. PMID- 1435928 TI - Mitral annular calcification and the risk of stroke. PMID- 1435929 TI - Hypernyctohemeral syndrome after chronotherapy for delayed sleep phase syndrome. PMID- 1435930 TI - A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites. AB - BACKGROUND: Borrelia burgdorferi, which causes Lyme disease, is transmitted by deer ticks (lxodes dammini) in the northeastern and midwestern United States. Although deer-tick bites are common in areas in which the disease is endemic, there is uncertainty about how to manage the care of persons who are bitten. METHODS: To assess the risk of infection with B. burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite, we conducted a double-blind, placebo-controlled trial in an area of southeastern Connecticut in which Lyme disease is endemic. Children and adults who had been bitten by deer ticks were randomly assigned to receive either amoxicillin or placebo for 10 days. Subjects were followed for one year for clinical manifestations of Lyme disease. Serum samples obtained at enrollment and six weeks and three months later were tested for antibodies against B. burgdorferi. RESULTS: Of the 387 subjects, 205 (53 percent) were assigned to receive amoxicillin and 182 (47 percent) to receive placebo. Of 344 deer ticks submitted and analyzed by the polymerase chain reaction, 15 percent were infected with B. burgdorferi. Erythema migrans developed in two subjects, both of whom had received placebo. There were no asymptomatic seroconversions and no late manifestations of Lyme disease. The risk of infection with B. burgdorferi in the placebo-treated subjects was 1.2 percent (95 percent confidence interval, 0.1 to 4.1 percent), which was not significantly different (P = 0.22) from the risk in the amoxicillin-treated subjects (0 percent; 95 percent confidence interval, 0 to 1.5 percent). CONCLUSIONS: Even in an area in which Lyme disease is endemic, the risk of infection with B. burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated. PMID- 1435931 TI - Plasma endothelin immunoreactivity in liver disease and the hepatorenal syndrome. AB - BACKGROUND: Severe renal vasoconstriction is central to the pathogenesis of renal failure in the hepatorenal syndrome. Endothelin-1 and endothelin-3 are potent, long-acting vasoconstrictors, and endothelin-1 has selective potency as a renal vasoconstrictor. These properties suggest a role for endothelins in the hepatorenal syndrome. METHODS: We measured plasma endothelin-1 and endothelin-3 concentrations using specific radioimmunoassays in subjects with hepatorenal syndrome, liver disease but normal renal function, chronic renal failure, acute renal failure, liver dysfunction and renal impairment, or normal liver and kidney function. RESULTS: The patients with the hepatorenal syndrome had markedly elevated mean (+/- SE) plasma concentrations of endothelin-1 (36 +/- 5 ng per liter [14.5 +/- 1.8 pmol per liter]) and endothelin-3 (43 +/- 3 ng per liter [16.3 +/- 1.0 pmol per liter]) as compared with the normal subjects (endothelin 1, 4 +/- 1 ng per liter [1.7 +/- 0.2 pmol per liter]; and endothelin-3, 18 +/- 1 ng per liter [6.8 +/- 0.4 pmol per liter]; P < 0.001) and with the patients in the other four groups (P < 0.001 to P < 0.05). The plasma endothelin-1, but not endothelin-3, concentrations in these four patient groups were significantly higher than in the normal subjects (P < 0.001 to P < 0.05). The concentrations of endothelin-1 in renal arterial plasma and renal venous plasma, measured in five patients with the hepatorenal syndrome and three with chronic liver disease and normal renal function, were 20 +/- 4 ng per liter (7.9 +/- 1.8 pmol per liter) and 24 +/- 4 ng per liter (9.5 +/- 1.5 pmol per liter), respectively (P < 0.05). CONCLUSIONS: The increase in plasma endothelin-1 and endothelin-3 concentrations in patients with the hepatorenal syndrome is consistent with the hypothesis that these substances have a role in the pathogenesis of the disease. PMID- 1435932 TI - Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. AB - BACKGROUND: Isolated thrombocytopenia accompanied by increased amounts of platelet-associated antibody is a common manifestation of human immunodeficiency virus (HIV) infection, and the thrombocytopenia often improves with zidovudine. It is not clear whether the mechanism of HIV-related thrombocytopenia primarily involves autoimmune destruction of platelets or reduced platelet production by megakaryocytes. METHODS: We studied the survival of 111In-labeled autologous platelets and performed platelet imaging in 24 men with isolated HIV-related thrombocytopenia (16 who received no treatment and 8 who received zidovudine). We also studied 20 HIV-infected men with normal platelet counts (10 who received no treatment and 10 who received zidovudine) and studied 12 healthy seronegative men as controls. RESULTS: Mean (+/- SD) platelet survival was significantly decreased in both the untreated and the zidovudine-treated patients with HIV-related thrombocytopenia (to 92 +/- 33 and 129 +/- 44 hours, respectively; both P < 0.001), as compared with the normal controls (198 +/- 15 hours). Mean platelet survival was also significantly decreased in the HIV-infected patients with normal platelet counts (untreated, 162 +/- 23 hours, P < 0.01; zidovudine treated, 166 +/- 35 hours, P < 0.05). Imaging studies, however, revealed no evidence of increased clearance of autologous platelets in the liver or spleen in any of these groups. Mean platelet production was significantly depressed in the untreated patients with thrombocytopenia (23,000 +/- 11,000 platelets per cubic millimeter per day, P < 0.001) as compared with the healthy controls (45,000 +/- 6,000 per cubic millimeter per day). Mean platelet production was significantly increased, however, in the men treated with zidovudine, both in those with thrombocytopenia (60,000 +/- 31,000 platelets per cubic millimeter per day, P < 0.01 vs. controls) and in those without thrombocytopenia (68,000 +/- 22,000 per cubic millimeter per day, P < 0.01). CONCLUSIONS: Although there was a moderate reduction in platelet survival in HIV-infected persons, these patients, regardless of platelet counts, also had decreased production of platelets, possibly due to viral infection of the megakaryocytes. Zidovudine appears to improve platelet production. PMID- 1435933 TI - The prognostic value of exercise testing in patients with cystic fibrosis. AB - BACKGROUND: Previous studies have shown female sex, impaired pulmonary function, older age, malnutrition, and colonization of the respiratory tract with Pseudomonas cepacia to be associated with a poor prognosis in patients with cystic fibrosis. We sought to determine the prognostic value of exercise testing in addition to the other prognostic factors. METHODS: A total of 109 patients with cystic fibrosis, 7 to 35 years old, underwent pulmonary-function and exercise testing in the late 1970s. They were followed for eight years to determine the factors associated with subsequent mortality. Survival rates were calculated with standard life-table methods. Cox proportional-hazards regression models were used to determine crude relative risks of mortality and relative risks adjusted for age, sex, body-mass index, forced expiratory volume in one second (FEV1) end-tidal partial pressure of carbon dioxide (PCO2) at peak exercise, and oxygen consumption at peak exercise (VO2 peak). RESULTS: Patients with the highest levels of aerobic fitness (VO2 peak, > or = 82 percent of predicted) had a survival rate of 83 percent at eight years, as compared with rates of 51 percent and 28 percent for patients with middle (VO2 peak, 59 to 81 percent of predicted) and lowest (VO2 peak, < or = 58 percent of predicted) levels of fitness, respectively. After adjustment for other risk factors, patients with higher levels of aerobic fitness were more than three times as likely to survive than patients with lower levels of fitness. Colonization with P. cepacia was associated with a risk of dying that was increased fivefold. Age, sex, body-mass index, FEV1, and end-tidal PCO2 at peak exercise were not independently correlated with mortality. CONCLUSIONS: Higher levels of aerobic fitness in patients with cystic fibrosis are associated with a significantly lower risk of dying. Although better aerobic fitness may simply be a marker for less severe illness, measurement of VO2 peak appears to be valuable for predicting prognosis. Further research is warranted to determine whether improving aerobic fitness through exercise programs will result in a better prognosis. PMID- 1435934 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 50-1992. A 54-year-old man with fever of unknown origin four years after a diagnosis of lymphocytic lymphoma. PMID- 1435935 TI - The hepatorenal syndrome--newer perspectives. PMID- 1435936 TI - Thrombocytopenia and the neglected megakaryocyte. PMID- 1435937 TI - Anaphylactic reactions to food. PMID- 1435938 TI - Anaphylactic reactions to food. PMID- 1435939 TI - Undiagnosed HIV infection in acute care hospitals. PMID- 1435940 TI - Fatal hospital-acquired multidrug-resistant tuberculous pericarditis in two patients with AIDS. PMID- 1435941 TI - Malabsorption of antituberculosis medications by a patient with AIDS. PMID- 1435942 TI - Third heart sounds in patients with valvular heart disease. PMID- 1435943 TI - Isolation, identification and biological activity of chlamydosporol from Fusarium culmorum HM-8. AB - An isolate of Fusarium culmorum (W. G. Smith), Sacc. HM-8 from a scabby wheat kernel sample from England produced a novel toxin when grown in culture on rice. This toxin, which was given the trivial name of HM-8, was purified, its toxic properties demonstrated and its structure determined by spectroscopic methods. Subsequent to preliminary reports of our findings, two other laboratories have independently isolated the same substance from F. chlamydosporum and F. acuminatum, and demonstrated the same structure by spectroscopic methods and X ray crystallography. Identity of the metabolite from F. culmorum HM-8 with the published structure is based on (1) identical elemental composition derived from both elemental analysis and high resolution mass spectrometry in electron impact and fast atom bombardment modes, (2) comparable melting point and chromatographic properties, and (3) the presence of characteristic absorption bands in the infrared, ultraviolet, and nuclear magnetic resonance (proton and carbon-13) spectra. Because both laboratories which subsequently isolated this metabolite have used the name chlamydosporol, it is being adopted here. The mass spectral properties of chlamydosporol are described. The derivative 8-O acetylchlamydosporol was prepared and characterized. Chlamydosporol caused food refusal and weight loss in rats, cytotoxic effects to cultured mouse and human fibroblast cells at concentrations of 2.5 micrograms/ml and 7.5 micrograms/ml, respectively, and mortality to chick embryos (10 to 70%) over a concentration range from 0.5 mg to 4 mg per egg. PMID- 1435944 TI - Automatic antifungal activity analyzing system on the basis of dynamic growth process of a single hypha. AB - A system for the evaluation of antifungal activity of volatile compounds has been developed that is based on dynamic growth of a single hypha. The newly developed system is composed of a reaction vessel under a microscope, automatic stage, charge coupled device (CCD) camera, TV monitor, video tape recorder (VTR), and a microcomputer. A fungus was inoculated in the reaction vessel containing agar medium and then was treated with an antifungal reagent in the gas phase either in batch or flow reaction manner. The apex of a growing hypha displayed on a TV monitor was followed automatically. From the ratio of the growth rate under exposure of a reagent (UEXPO) to the growth rate before the exposure (UPRE), the antifungal activity was expressed quantitatively. PMID- 1435946 TI - Paronychia and black discoloration of a thumb nail caused by Curvularia lunata. AB - Chronic paronychia associated with black discoloration of the left thumb nail in a 51 year old female caused by Curvularia lunata is reported for the first time. The keratolytic activity of the fungus in the nail and its complete clearance by topical clotrimazole are reported. PMID- 1435945 TI - Evaluation of antifungal activity of antimycotics by automatic analyzing system. AB - Antifungal activity of several antimycotics has been evaluated using an automatic analyzing system (AAS), which is composed of a specially designed reaction vessel, microscopic observation system, image analyzing system, and computer program for automatic tracing of hypha growth. The agar plate was prepared on the ceiling of the reaction vessel, and spore mass of a fungus (Aspergillus niger) was inoculated onto it. After the preincubation at 28 degrees C for 24 h the reaction vessel was set on a microscope stage and connected to the liquid flow system. An appropriate hypha was selected for the measurement of growth process during the following steps: first contact with saline for 30 min for the adaptation, the second contact with same saline for 30 min, contact with saline containing an antimycotic substance for 60 min, and contact with flushing saline for 60 min. During a sequence of these steps, the apical tip of a growing hypha displayed on a TV monitor was followed automatically. The dynamic response of hypha to an agent was analyzed by several parameters. Morphological changes of the hypha caused by respective agents were recorded on VTR for further analysis. By using this system, the antifungal activity of antimycotics could be quantitatively determined within several hours. PMID- 1435947 TI - Properties of a partially purified acid phosphatase from pathogenic Nocardia brasiliensis. AB - Like many other bacteria, Nocardia sp. possess acid phosphatase activity. In N. brasiliensis, a human and animal pathogen, this activity was resolved into two enzyme forms by native gel electrophoresis. One (isozyme I) was partially purified and characterized. It exhibited an estimated molecular weight on SDS PAGE of 50 kDa, a pH optimum of 5.2, and a Km value of 1.25 mM for p nitrophenylphosphate. The N. brasiliensis enzyme was stable at 4 degrees C for at least 24 h, but readily inactivated at 60 degrees C. Ammonium molybdate, sodium fluoride and L-(+)-tartrate were found to be potent inhibitors of the enzyme. Although its function is presently unknown, by analogy to other bacterial systems it could be envisioned to play an important role in the physiology and pathogenicity of the microorganism. PMID- 1435948 TI - Light and electron microscopic studies on experimental nocardia-toxicosis in mice. AB - An exotoxin (HS-6) produced by Nocardia otitidiscaviarum isolated from certain lesions of cutaneous nocardiosis of a male 82-year-old patient induced severe injuries in the pancreas, liver, stomach, small intestine, heart, thymus and kidney of male ICR mice. Mice given Nocardia-free preparation of HS-6 at a dose of 1 mg/kg of body weight developed several autophagic vacuoles in the pancreas and liver within 20 min after the i.p. injection. Thereafter, the autophagic vacuoles increased in number and size with time. About 24 hr after the administration of HS-6, the liver showed marked accumulation of fat droplets in the cytoplasm of the hepatocytes. Although they contained abundant autophagic vacuoles in the regions of RER, there were no lipomatoses in the acinar cells of the pancreas, those of the chief cells and smooth muscle cells of the stomach, Paneth cells, goblet cells, smooth muscle cells of the small intestine, and plasma cells in the digestive tract. Biochemical examinations revealed that HS-6 had no significant effect on the protein synthesis of reticulocytes. Inoculation of the Nocardia into the mouse peritoneal cavities caused marked granulomatoses in the pancreas, liver and regional lymph nodes, but did not develop autophagic vacuoles in RER regions of these organs. PMID- 1435950 TI - Partial suppression of cell mediated immunity in chromoblastomycosis. AB - The cellular immune response of 8 patients from the Brazilian Amazon region with chromoblastomycosis was analyzed. Primary immunological responses of patients were tested by contact sensitization to 2,4-dinitro-chlorobenzene (DNCB), or rejection of first set skin allografts. 2 of 8 patients were reactive to DNCB after sensitization, and skin allograft rejection occurred in an average of 14 days. Capacity of patients to mount recall immunological responses was measured by skin testing with two fungal antigens and three bacterial antigens. Delayed skin reaction to trichophytin and candida antigens was negative in the majority of the patients. However, reactivity to mycobacterial (tuberculin), and bacterial (staphylococcal, streptococcal) antigen was high, or only slightly diminished respectively. The data suggest that patients with chromoblastomycosis have suppressed nonspecific, cell mediated immunity for some antigens (skin allografts, DNCB, fungal antigens), while reactivity to bacterial and mycobacterial antigens is not impaired. PMID- 1435949 TI - Immunosuppressive effect of paracoccidioidomycosis sera on the proliferative response of normal mononuclear cells. Identification of a Paracoccidioides brasiliensis 34-kDa polypeptide in circulating immune complexes. AB - In this paper we relate that sera from paracoccidioidomycosis patients inhibited the mitogen-induced proliferative responses of normal mononuclear cells. Treatment of these sera with 2.5% polyethyleneglycol (PEG), a method classically used to precipitate immune complexes, significantly reduced their inhibitory activity. Immunoblot analysis of the PEG precipitates identified a 34-kDa polypeptide, recognized by rabbit anti-P. brasiliensis IgG. Patient mononuclear cells showed partial restoration of their proliferative capacity after 24 h culture in medium alone, which suggests release of membrane-bound molecules in the culture medium. These findings indicate that circulating P. brasiliensis antigens, complexed or not with antibodies, may play a negative immunoregulatory effect in the mitogen-induced proliferative responses of paracoccidioidomycosis patients. PMID- 1435951 TI - Incidence and significance of opportunistic fungi in leukemia patients in India. AB - Twenty-four patients with acute leukemia were investigated for the incidence of opportunistic fungi. Culture isolations of the sputum and urine samples revealed significant levels of Candida in 14 patients; Candida albicans, C. tropicalis and C. pseudotropicalis were the predominant ones isolated. Aspergillus flavus was isolated from blood in two cases and C. albicans and a black yeast from the blood of another two. Serological studies showed fungal antibodies in seven patients; precipitins against Candida were detected in five and Aspergillus in two. Both of the Aspergillus positive cases and two patients who had rising antibodies against Candida died during the course of investigation. In this study 13 of 24 patients developed oral candidiasis. PMID- 1435952 TI - Evaluation of two vaccines for the treatment of pythiosis insidiosi in horses. AB - Two vaccines to treat phythiosis insidiosi in horses were evaluated in 71 Costa Rican horses between 1982 to 1988. One vaccine used a cell-mass (CMV) as antigen and the other a soluble concentrated antigen (SCAV). Both vaccines cured horses infected with Pythium insidiosum (p value approximately 14%). The age of lesions prior to vaccination was important in the response of the horses to immunotherapy. All horses with lesions 0.5 months or less in duration were cured regardless of the vaccine used. Horses with lesions two or more months old did not respond to either vaccine. The age of the horses did not have any influence on their response to the vaccinations. The CMV produced a prominent inflammatory reaction at the side of injection, while the SCAV gave a low inflammatory reaction. In addition, the CMV lost its effectiveness two to three weeks after its preparation. By contrast, the SCAV maintained its ability to cure horses even after 18 months. Immunotherapy using SCAV can thus be used as the vaccine of choice in early cases of equine cutaneous pythiosis insidiosi. PMID- 1435953 TI - Growth of Cryptococcus neoformans in a thiamine-free medium. AB - The growth of Cryptococcus neoformans in a minimal liquid synthetic medium with or without thiamine (10 micrograms/ml) was investigated. In these media the presence or absence of thiamine had no effect on the development of C. neoformans. To check these results, we performed a series of experiments on a solid form of the minimal synthetic medium. In this study a series of six serial transfers were carried out to starve the cells of nutrients that may have been carried over from their growth on rich media. In each of the transfers on the solid synthetic medium, C. neoformans showed a similar and scarce growth. This finding indicates that C. neoformans could be autotrophic in respect to thiamine. PMID- 1435955 TI - Disseminated Aspergillus terreus infection in a caged pigeon. AB - Disseminated aspergillosis due to Aspergillus terreus was diagnosed in a young pigeon kept by a bird fancier. The fungus was isolated in heavy growth from the infected tissues on Sabouraud medium at 37 degrees C. Microscopic examination of the squeeze preparation of the air sacs revealed the presence of typical conidiophores of an Aspergillus sp. Histologically, branched, septate hyphae morphologically indistinguishable from Aspergillus were detected in the air sacs and lungs. The clinical, mycological and pathological findings are discussed. The role of A. terreus as an opportunistic pathogen should be studied in various clinical conditions of mammals and avians. PMID- 1435954 TI - Cryptococcus neoformans varieties as agents of cryptococcosis in Brazil. AB - The study of the clinical isolates of Cryptococcus neoformans from 83 Brazilian patients with disseminated cryptococcosis showed that 75 were C. neoformans var. neoformans and 8 were var. gattii. Twenty-seven isolates were serotyped; all 19 var. neoformans were serotype A and all 8 var. gattii were serotype B. The correlation of the varieties of C. neoformans with the presence or not of hosts predisposing conditions to the mycosis showed that: (1) cryptococcosis caused by gattii variety occurred in 7 (58.3%) of the 12 nonimmunosuppressed patients, and (2) cryptococcosis caused by neoformans variety occurred in 65 (98.5%) of the 66 AIDS patients and in all 5 patients with other immunosuppressive conditions. The comparison of the distribution of the gattii and neoformans varieties between the nonimmunosuppressed and immunosuppressed patients showed a significant statistical difference (p < 0.01). PMID- 1435956 TI - Studies on the relationship between the estrous cycle of BALB/c mice and their resistance to Paracoccidioides brasiliensis infection. AB - A relationship between the estrous cycle and non-specific host resistance to Paracoccidiodes brasiliensis yeast cells was examined by using both sexes of adult BALB/c mice. They were divided into 6 groups, including a male group and females at proestrus, estrus, metestrus-I, metestrus-II and diestrus. The mice received yeast cells through three different inoculation routes; intravenous, intraperitoneal and intratracheal. In all of the inoculation routes, the clearance of the yeast cells was influenced by the estrous cycle. The female mice at estrus, which might have high blood estrogen levels, showed a marked clearance of the yeast cells from the blood, peritoneal cavity and lungs. These results suggested that non-specific host resistance to the yeast cells was enhanced by estrogen. All female groups inoculated by the three routes showed higher clearance of the yeast cells than the male group. PMID- 1435957 TI - Purification and partial characterization of two extracellular keratinases of Scopulariopsis brevicaulis. AB - Two extracellular keratinases of Scopulariopsis brevicaulis were purified and partially characterized. The enzymes were isolated by the techniques of gel filtration chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). These keratinases (K I & K II) were purified approximately 33 and 29 fold, respectively. SDS-PAGE of the products of gel filtration chromatography (K I & II) produced only one band each, suggesting homogeneity. The optimum pH for both keratinases was 7.8, while the optimum temperatures were 40 degrees C (K I) and 35 degrees C (K II). Estimated molecular weights were 40-45 KDa and 24-29 KDa for K I & K II respectively. Both keratinases were inhibited by phenylmethylsulfonyl fluoride which suggests a serine residue at or near an active site. PMID- 1435958 TI - A biological assay for the detection of Myrothecium spp. produced macrocyclic trichothecenes. AB - A rapid, inexpensive bioassay to detect Myrothecium spp.-produced macrocyclic trichothecenes was developed. Media containing Myrothecium isolates were inoculated with Chlorella vulgaris, Ustilago maydis and Trichoderma viride. Based on width of the inhibition zone, isolates could be classified as highly toxigenic, non-toxigenic and intermediate. Whereas, C. vulgaris and U. maydis showed significant differences in their response to toxigenic and non-toxigenic isolates, T. viride did not. Production of roridins and verrucarins by the toxigenic isolates (by bioassay) was confirmed by thin layer chromatography and high performance liquid chromatography. This bioassay system, combined with confirmation chemical analyses, increases our ability to detect toxigenic fungal isolates. PMID- 1435959 TI - Feeding differently processed soya bean. Part 1. Effect on performance, protein utilization, relative organ weights, carcass traits and economics of producing broiler-chickens. AB - The comparative utilization of differently processed (roasted, cooked and oil cake) soya bean base diets and groundnut cake diet were evaluated in a feeding trial using 100 day-old Anak broiler-chicks. The response criteria included performance, protein utilization, relative organ weights, carcass traits and economy of production. At the end of the feeding trial, the average weight gains of chicks fed processed soya bean diets were significantly (P less than 0.05) higher than those fed groundnut cake and raw soya bean diets. Both feed consumption and efficiency were significantly (P less than 0.05) enhanced by processing. For example, feed consumption was highest in the chicks fed soya bean oil cake and least in those fed raw bean. Feed efficiency was best in chicks fed roasted soya bean. The relative weights [g/100 g body wt.] of the liver, kidneys, lungs, heart, gizzard and bursa were not significantly affected by the differently processed soya bean while the raw bean (unprocessed) significantly (P less than 0.01) increased pancreas weight. The dressed weight [%], eviscerated weight [%] and the relative weight of the thigh, drumsticks, chest, back and head were not significantly influenced by the dietary treatments. However, the relative weights of the shank and belly fat were significantly (P less than 0.05) affected. Cost-benefit analysis showed that the processed soya bean gave higher profit than groundnut cake diet. Among the soya bean diets, profit was in the order: roasted greater than cooked greater than oil cake greater than raw bean. PMID- 1435961 TI - Problems of Drug Dependence 1991. Proceedings of the 53rd annual scientific meeting of the Committee on Problems of Drug Dependence, Inc. Richmond, Virginia, June 1991. PMID- 1435960 TI - Feeding differently processed soya bean. Part 2. An assessment of haematological responses in the chicken. AB - The use of differently processed soya bean as a major source of dietary protein was evaluated in a haematological study using broiler chickens in which groundnut cake (GNC), raw soya bean (RSB), roasted soya bean (RtSB), cooked soya bean (CSB) and soya bean oil cake (SBC) were fed on equi-protein basis. The results showed that: 1. Red blood cell (RBC) count and haemoglobin content of blood significantly (P less than 0.05) increased in chicks fed RSB relative to the other soya bean diets. Feeding differently processed soya bean significantly (P less than 0.05) influenced mean cell haemoglobin (MCH) and mean corpuscular volume (MCV) while the mean corpuscular haemoglobin concentration (MCHC) was not significantly influenced. 2. Both the total white blood cell (WBC) count and the monocytes were significantly (P less than 0.05) influenced by the dietary treatments. Chicks fed processed soya bean generally had higher number of monocytes. 3. Physical properties determined were specific gravity and erythrocyte sedimentation rate. The latter was significantly (P less than 0.05) lower in all the processed soya bean-fed chicks. 4. Minerals determined in blood were Na, K, Ca, Mg, Fe, Cu and P. Of all these, chicks fed RSB had significantly (P less than 0.01) lower levels of blood Mg and marked decrease in Ca. PMID- 1435962 TI - Biomedical research and scientific citizenship: the price of progress. PMID- 1435963 TI - DSM-IV substance use disorders: the view from DSM-III-R. PMID- 1435964 TI - Effects of drugs of abuse and treatment agents in women. PMID- 1435965 TI - Cardiovascular effects of cocaine in pregnancy and on the fetus. PMID- 1435966 TI - Effects of cocaine and other drugs on the infant. PMID- 1435967 TI - Fetal alcohol syndrome: early and long-term consequences. PMID- 1435968 TI - Hallucinogens and serotonergic mechanisms. AB - Classical hallucinogens possess 5-HT2 agonist activity; certain structurally related agents are antagonists, but there is no evidence that the antagonists are hallucinogenic. Both the discriminative stimulus and human hallucinogenic potencies of the agonists are significantly correlated with 5-HT2 receptor affinity when [3H]-ketanserin is used as radioligand (Glennon et al., 1984). These agents appear to bind with higher affinity when [3H]DOB, an agent that apparently labels the agonist high-affinity state of 5-HT2 receptors, is used as radioligand (Sadzot et al., 1989). For a series of DOB-related agents, 5-HT2(KET) affinity can be modeled by the lipophilicity of the 4-position substituent; lipophilicity alone does not completely account for the affinity of 5-HT2 agonists. Using [3H]DOB as radioligand to minimize differences observed between agonists and antagonists, 5-HT2 affinity is related both to the lipophilicity and electron withdrawing nature of the 4-position substituents. The difference between 5-HT2(KET) and 5-HT2(DOB) binding may be related to the intrinsic activity of DOB-related agents. Serotonin, with an intrinsic activity of 1.0, is not hallucinogenic whereas hallucinogens may be hallucinogenic because they are high-affinity 5-HT2 partial agonists. PMID- 1435969 TI - Serotonin and alcohol drinking. PMID- 1435970 TI - Pharmacotherapy of substance abuse with serotonergic drugs. PMID- 1435971 TI - Behavioral strategies for the evaluation of new pharmacotherapies for drug abuse treatment. PMID- 1435972 TI - Preclinical methods for the development of pharmacotherapies for cocaine abuse. PMID- 1435973 TI - A laboratory model for evaluating potential treatment medications in humans. PMID- 1435974 TI - Clinical parallels of chronic drug self-administration models for treatment evaluation. PMID- 1435975 TI - Use of cocaine-discrimination techniques for preclinical evaluation of candidate therapeutics for cocaine dependence. PMID- 1435976 TI - The use of human drug discrimination studies in medication development. PMID- 1435977 TI - Effects of magnesium on cocaine-reinforced responding in mice, rats and squirrel monkeys. PMID- 1435978 TI - Access schedules of oral cocaine and ethanol in rats. PMID- 1435979 TI - The National Institute on Drug Abuse 1991: new faces, responsibilities, and opportunities. PMID- 1435980 TI - Effects of endogenous calcium regulating peptides on opiate actions. PMID- 1435981 TI - Effects of opiates, opioid antagonists and cocaine on the endogenous opioid system: clinical and laboratory studies. PMID- 1435982 TI - The continuing interrelationship of CPDD and NIDDK. PMID- 1435983 TI - Biological evaluation of compounds for their physical dependence potential and abuse liability, XIV. Animal Testing Committee of the Committee on Problems of Drug Dependence, Inc. (1991). PMID- 1435984 TI - Dependence studies of new compounds in the rhesus monkey and mouse (1991). PMID- 1435985 TI - Potent analgesia, respiratory depression, dependence, abuse liability-clue to separability. PMID- 1435986 TI - Evaluation of new compounds for opioid activity (1991). PMID- 1435987 TI - Three generations of electrophilic affinity ligands for the phencyclidine binding sites. PMID- 1435988 TI - The cannabinoid receptor-pharmacologic identification, anatomical localization and cloning. PMID- 1435989 TI - Overview of opioid medicinal chemistry. PMID- 1435990 TI - Progress in Case Management. Technical review. Bethesda, Maryland, February 4-5, 1992. PMID- 1435991 TI - Transitional case management: a service model for AIDS outreach projects. PMID- 1435992 TI - Application of case management to drug abuse treatment: overview of models and research issues. PMID- 1435993 TI - Delivering case management using a community-based service model of drug intervention. PMID- 1435994 TI - Case management to enhance AIDS risk reduction for injection drug users and crack cocaine users: practical and philosophical considerations. AB - The AIDS intervention model described herein represents a new "mixed" model of case management, one that combines AIDS risk-reduction education with a modified version of the traditional broker of services model. The case management component of the model is designed to heed and address those immediate needs that may distract a person from attending to the AIDS risk-reduction messages. The educational component of the model can help a person develop interest in the case management services. The result is a model that, theoretically, can have a greater impact than either component alone would have. The advantages of the model are its flexibility, its ability to quickly assess and address clients' concerns, and its short duration that enhances the likelihood that drug users will complete the process. PMID- 1435995 TI - Case management services for HIV-seropositive IDUs. PMID- 1435996 TI - Case management models for homeless persons with alcohol and other drug problems: an overview of the NIAAA research demonstration program. PMID- 1435997 TI - Integrating qualitative and quantitative components in evaluation of case management. PMID- 1435998 TI - Case management systems represented in the NIDA-supported "Perinatal-20" treatment research demonstration projects. PMID- 1435999 TI - Case management: a telecommunication practice model. PMID- 1436000 TI - Intensive case management for youth with serious emotional disturbance and chemical abuse. PMID- 1436001 TI - Development and implementation of an interorganizational case management model for substance users. PMID- 1436002 TI - Managed care and case management of substance abuse treatment. AB - Managed care has become an important subject for health service research and is used increasingly by health care payers to control health care use and costs. Health services research on managed care has relevance to the evaluation of case management of persons with substance abuse problems. Two issues in managed care that are particularly relevant to case management are the lack of explicit, widely accepted criteria for managed care and the lack of demonstrated cost savings attributable to managed care. Thorough, systematic evaluative research needs to be done before these issues are well understood. PMID- 1436003 TI - Assertive community treatment with a parolee population: an extension of case management. PMID- 1436004 TI - TASC: case management models linking criminal justice and treatment. PMID- 1436005 TI - Case management community advocacy for substance abuse clients. PMID- 1436006 TI - Accessing additional community resources through case management to meet the needs of methadone clients. PMID- 1436007 TI - A strengths-based model of case management/advocacy: adapting a mental health model to practice work with persons who have substance abuse problems. PMID- 1436008 TI - Case management: an alternative approach to working with intravenous drug users. PMID- 1436009 TI - Statistical Issues in Clinical Trials for Treatment of Opiate Dependence. Technical review. Bethesda, Maryland, December 2-3, 1991. PMID- 1436010 TI - Analysis of clinical trials for treatment of opiate dependence: what are the possibilities? PMID- 1436011 TI - Toward a dynamic analysis of disease-state transition monitored by serial clinical laboratory tests. PMID- 1436012 TI - Background and design of a controlled clinical trial (ARC 090) for the treatment of opioid dependence. AB - This study represents the largest clinical trial reported to date that demonstrated the efficacy of buprenorphine for opioid dependence treatment (Johnson et al. 1992). Although the study design was adequate to demonstrate differences between treatment groups, there has not been a consensus regarding the most appropriate method for analyzing various outcome measures of this and similar studies. To present a comprehensive review of these methods, other chapters in this monograph focus on various analytical techniques for assessing one of these measures--urine toxicology screens--for illicit opioids. PMID- 1436013 TI - A Markov model for NIDA data on treatment of opiate dependence. PMID- 1436014 TI - Design of clinical trials for treatment of opiate dependence: what is missing? PMID- 1436015 TI - Efficacy of urinalysis in monitoring heroin and cocaine abuse patterns: implications in clinical trials for treatment of drug dependence. AB - Urinalysis can be used as an objective criterion for monitoring the outcome of a treatment program or a clinical trial. Important factors to consider when implementing a drug testing program include standardization of assay technology and cutoffs between participating centers and selection of identical testing schedules. Also, it is vitally important to minimize the amount of safe time (time that drug use can go undetected) occurring in a testing schedule. The detection times for cocaine and heroin have been shown to vary with selection of cutoff and with the drug dose. Obviously, the selection of cutoffs is under program control, whereas the amount of illicit drug use is under subject control. Fortunately, changes in the illicit drug dose by the subject demonstrate a log linear relationship to detection time. Hence, a higher drug dose by the subject only extends the detection time slightly (and improves the probability of detection) without greatly increasing the risks of drug carryover from one urine test to another. The most efficient testing schedule for judging the outcome of clinical trials for cocaine and heroin appears to be a 3-days-a-week schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday). When different schedules were challenged by simulating random times at which cocaine use might occur during the week, the 3-days-per-week schedule was the most efficient without the risk of carryover. The 3-days-per-week schedule also performed better than 1-day-per-week when multiple random drug use was simulated. Overall, the 3 days-per-week testing schedule with specified assay technology and cutoffs was the best compromise for maximizing detection of drug use, minimizing carryover, and providing a standardized methodology for outcome comparison between programs. PMID- 1436016 TI - Drug dependence (addiction) and its treatment. PMID- 1436017 TI - A Bayesian nonparametric approach to analysis of treatment for drug-dependence data. PMID- 1436018 TI - Three estimators of the probability of opiate use from incomplete data. PMID- 1436020 TI - Infectious diseases are not banished. PMID- 1436019 TI - Issues in the analysis of clinical trials for opiate dependence. PMID- 1436021 TI - NHS opens meta-analysis centre. PMID- 1436022 TI - Racial tensions entangle NIH in dispute over AIDS drug. PMID- 1436024 TI - Consciousness. PMID- 1436023 TI - Mail-order notification would replace permits for US field tests. PMID- 1436025 TI - Struggles to correct published errors. PMID- 1436026 TI - G proteins. Visual differences. PMID- 1436027 TI - Drug ring bust. PMID- 1436028 TI - Palaeoanthropology. Second gorilla or third chimp? PMID- 1436029 TI - A rete in the right whale. PMID- 1436030 TI - Childhood thyroid cancer in Belarus. PMID- 1436031 TI - Childhood thyroid cancer in Belarus. PMID- 1436032 TI - DNA fingerprints of cell lines. PMID- 1436033 TI - Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. AB - Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional growth factor that has profound regulatory effects on many developmental and physiological processes. Disruption of the TGF-beta 1 gene by homologous recombination in murine embryonic stem cells enables mice to be generated that carry the disrupted allele. Animals homozygous for the mutated TGF-beta 1 allele show no gross developmental abnormalities, but about 20 days after birth they succumb to a wasting syndrome accompanied by a multifocal, mixed inflammatory cell response and tissue necrosis, leading to organ failure and death. TGF-beta 1-deficient mice may be valuable models for human immune and inflammatory disorders, including autoimmune diseases, transplant rejection and graft versus host reactions. PMID- 1436034 TI - Molecular structure of the acyl-enzyme intermediate in beta-lactam hydrolysis at 1.7 A resolution. AB - The X-ray crystal structure of the molecular complex of penicillin G with a deacylation-defective mutant of the RTEM-1 beta-lactamase from Escherichia coli shows how these antibiotics are recognized and destroyed. Penicillin G is covalently bound to Ser 70 0 gamma as an acyl-enzyme intermediate. The deduced catalytic mechanism uses Ser 70 0 gamma as the attacking nucleophile during acylation. Lys 73 N zeta acts as a general base in abstracting a proton from Ser 70 and transferring it to the thiazolidine ring nitrogen atom via Ser 130 0 gamma. Deacylation is accomplished by nucleophilic attack on the penicilloyl carbonyl carbon by a water molecule assisted by the general base, Glu 166. PMID- 1436035 TI - Wing bone stresses in free flying bats and the evolution of skeletal design for flight. AB - The primary mechanical functions of limb bones are to resist deformation, and hence provide stiff levers against which muscles can act, and to be sufficiently strong to prevent breaking under static or dynamic loads which arise from normal and accidental activities. If bones perform these functions with a minimum amount of material, the energetic costs associated with building, maintaining and transporting the skeleton will be minimized. Appropriate skeletal architecture for minimizing mass while maximizing strength depends on forces imposed on structural elements. In the evolutionary acquisition of flight in the bat lineage, the forelimb skeleton must have come to experience locomotor-forces that differed from those engendered by the terrestrial locomotion of non-flying bat relatives. Here we successfully measure in vivo strain on the wing bones of flying mammals. Our data demonstrate that torsion and shear are unique and crucial features of skeletal biomechanics during flight, and suggest that the evolution of skeletal design in bats and other flying vertebrates may be driven by the need to resist these loads. PMID- 1436036 TI - Quantal transmitter secretion from myocytes loaded with acetylcholine. AB - It is well known that transmitter secretion requires specialized secretory organelles, the synaptic vesicles, for the packaging, storage and exocytotic release of the transmitter. Here we report that when acetylcholine (ACh) is loaded into an isolated Xenopus myocyte, there is spontaneous quantal release of ACh from the myocyte which results in activation of its own surface ACh channels and the appearance of membrane currents resembling miniature endplate currents. This myocyte secretion probably reflects Ca(2+)-regulated exocytosis of ACh filled cytoplasmic compartments. Furthermore, step depolarization of the myocyte membrane triggers evoked ACh release from the myocyte with a weak excitation secretion coupling. These findings suggest that quantal transmitter secretion does not require secretory pathways unique to neurons and that the essence of presynaptic differentiation may reside in the provision of transmitter supply and modification of the preexisting secretion pathway. PMID- 1436037 TI - Patterns of elevated free calcium and calmodulin activation in living cells. AB - The temporal and spatial dynamics of intracellular signals and protein effectors are being defined as a result of imaging using fluorescent reagents within living cells. We have described a new class of fluorescent analogues termed optical biosensors, which sense chemical or molecular events through their effects on protein transducers. One example of this new class of indicators is MeroCaM, an environmentally sensitive fluorophore which when it is attached to calmodulin reflects the activation of calmodulin by calcium in vitro. We report here that the rise in free calcium and MeroCaM activation occur in the same period during serum stimulation of quiescent fibroblasts. MeroCaM activation also correlates with the spatial pattern of increased free calcium and the contraction of transverse fibres during wound healing. Finally, migrating fibroblasts in the later stages of wound-healing exhibit an increasing gradient of free calcium and MeroCaM activation from the front to the rear. PMID- 1436038 TI - Pol of gag-pol fusion protein required for encapsidation of viral RNA of yeast L A virus. AB - Double-stranded RNA viruses have an RNA-dependent RNA polymerase activity associated with the viral particles which is indispensable for their replication cycle. Using the yeast L-A double-stranded RNA virus we have investigated the mechanism by which the virus encapsidates its genomic RNA and RNA polymerase. The L-A gag gene encodes the principal viral coat protein and the overlapping pol gene is expressed as a gag-pol fusion protein which is formed by a -1 ribosomal frameshift. Here we show that Gag alone is sufficient for virus particle formation, but that it fails to package the viral single-stranded RNA genome. Encapsidation of the viral RNA requires only a part of the Pol region (the N terminal quarter), which is presumably distinct from the RNA polymerase domain. Given that the Pol region has single-stranded RNA-binding activity, these results are consistent with our L-A virus encapsidation model: the Pol region of the fusion protein binds specifically to the viral genome (+) strand, and the N terminal gag-encoded region primes polymerization of Gag to form the capsid, thus ensuring the packaging of both the viral genome and the RNA polymerase. PMID- 1436039 TI - Lipid modification at the N terminus of photoreceptor G-protein alpha-subunit. AB - Myristate is a fatty acid (fourteen-carbon chain with no double bonds, C14:0) linked to the amino-terminal glycine of several proteins, including alpha subunits of heterotrimeric (alpha/beta gamma) G proteins. We report here a novel modification at the N terminus of the alpha-subunit of the photoreceptor G protein transducin, T alpha, with heterogeneous fatty acids composed of laurate (C12:0), unsaturated C14:2 and C14:1 fatty acids, and a small amount (approximately 5%) of myristate. Both the GTPase activity of T alpha/T beta gamma and the T beta gamma-dependent ADP-ribosylation of T alpha catalysed by pertussis toxin were inhibited by the lauroylated and myristoylated N-terminal peptide of T alpha. The myristoylated peptide gave 50% inhibition at a 3.5 to approximately 4.5-fold lower concentration than the lauroylated peptide in each assay, indicating that the strength of the interaction between T alpha and T beta gamma is altered by heterogeneous fatty acids linked to T alpha. This suggests that a looser subunit interaction in transducin which is due to an abundance of N-linked fatty acids other than myristate would favour the rapid turnover and catalysis essential for the visual excitation in photoreceptor cells. PMID- 1436040 TI - Crystal structure of a streptococcal protein G domain bound to an Fab fragment. AB - Protein G is a cell-surface protein from Streptococcus which binds to IgG molecules from a wide range of species with an affinity comparable to that of antigen. The high affinity of protein G for the Fab portion of IgG poses a particular challenge in molecular recognition, given the variability of heavy chain subclass, light chain type and complementarity-determining regions. Here we report the crystal structure of a complex between a protein G domain and an immunoglobulin Fab fragment. An outer beta-strand in the protein G domain forms an antiparallel interaction with the last beta-strand in the constant heavy chain domain of the immunoglobulin, thus extending the beta-sheet into the protein G. The interaction between secondary structural elements in Fab and protein G provides an ingenious solution to the problem of maintaining a high affinity for many different IgG molecules. The structure also contrasts with Fab-antigen complexes, in which all contacts with antigen are mediated by the variable regions of the antibody, and to our knowledge provides the first details of interaction of the constant regions of Fab with another protein. PMID- 1436041 TI - France's blood scandal draws blood. AB - The trial in France of four government officials for complicity in the use of contaminated blood may have ended with the verdicts announced last Friday, but the recriminations will continue. PMID- 1436042 TI - Groups sue to end fetal tissue ban. PMID- 1436043 TI - NIH and Army meet on breast cancer windfall. PMID- 1436044 TI - Verdict in French blood trial shames science. PMID- 1436045 TI - US panel rejects hiding source of allegations of misconduct. PMID- 1436046 TI - Sizing-up the brain. PMID- 1436047 TI - Sizing-up the brain. PMID- 1436048 TI - Sizing-up the brain. PMID- 1436049 TI - Motive to sin. PMID- 1436050 TI - The 'far east' of biological ethics. AB - The ethics of biological research, and its general impact, are hotly debated in the West. Japanese silence on the issues is counterproductive. Will the Human Genome Project provide the catalyst for change? PMID- 1436051 TI - Cell biology. Progress by poisoning. PMID- 1436052 TI - Correct structure prediction? PMID- 1436053 TI - Correlations in intronless DNA. PMID- 1436054 TI - Antibodies from libraries. PMID- 1436055 TI - Sizing single DNA molecules. PMID- 1436056 TI - More on bear droppings. PMID- 1436057 TI - A second-generation linkage map of the human genome. AB - A linkage map of the human genome has been constructed based on the segregation analysis of 814 newly characterized polymorphic loci containing short tracts of (C-A)n repeats in a panel of DNAs from eight large families. Statistical linkage analysis placed 813 of the markers into 23 linkage groups corresponding to the 22 autosomes and the X chromosome; 605 show a heterozygosity above 0.7 and 553 could be ordered with odds ratios above 1,000:1. The distance spanned corresponds to approximately 90% of the estimated length of the human genome. PMID- 1436058 TI - Crystal structure of staphylococcal enterotoxin B, a superantigen. AB - The three-dimensional structure of staphylococcal enterotoxin B, which is both a toxin and a super-antigen, has been determined to a resolution of 2.5 A. The unusual main-chain fold containing two domains may represent a general motif adopted by all staphylococcal enterotoxins. The T-cell receptor binding site encompasses a shallow cavity formed by both domains. The MHCII molecule binds to an adjacent site. Another cavity with possible biological activity was also identified. PMID- 1436059 TI - Connectivity of chemosensory neurons is controlled by the gene poxn in Drosophila. AB - The function of the nervous system depends on the formation of a net of appropriate connections, but little is known of the genetic program underlying this process. In Drosophila two genes that specify different types of sense organs have been identified: cut (ct), which specifies the formation of external sense organs as opposed to chordotonal organs, and pox-neuro (poxn), which specifies the formation of poly-innervated (chemosensory) organs as opposed to mono-innervated (mechanosensory) organs. Whether these genes are also involved in specifying the connectivity of the corresponding neurons is not known. The larval sense organs are unsuitable for analysis of the axonal pathway and connections and so we have investigated the effect of poxn on the adult. Here we show that overexpression of poxn induces the morphological transformation of mechanosensory into chemosensory bristles on the legs and that the neurons innervating the morphologically transformed bristles follow pathways and establish connections that are appropriate for chemosensory bristles. PMID- 1436060 TI - Enterotoxin residues determining T-cell receptor V beta binding specificity. AB - Superantigens such as the staphylococcal enterotoxins bind to major histocompatibility complex (MHC) class II molecules and activate T cells through a specific interaction between the V beta region of the T-cell antigen receptor (TCR) and the toxin. The TCR beta-chain alone is sufficient to produce the interaction with the enterotoxin-class II complex. Identification of the regions of enterotoxins that interact with TCR has so far proved equivocal because of difficulties in distinguishing between direct effects on T-cell recognition and indirect effects resulting from alteration of binding to class II. For example, amino-terminal truncations of SEB abrogated T-cell stimulation whereas carboxy terminal truncation of SEA stopped its mitogenic activity. The most comprehensive study to date, accounting for both enterotoxin binding to class II and enterotoxin interactions with the TCR, identified two functionally important regions for SEB binding to TCR. Although the amino-acid sequences of staphylococcal enterotoxins A and E are 82% identical, they activate T cells bearing different V beta elements. We have assayed the binding of cells coated with these enterotoxins to soluble secreted TCR beta-chain protein and find that V beta 3 binds enterotoxin A but not E, whereas V beta 11 binds enterotoxin but not A. To map the amino-acid residues responsible for these different binding specificities, we prepared a series of hybrids between the two staphylococcal enterotoxins. We report that just two amino-acid residues near the carboxy terminus of the enterotoxins are responsible for the discrimination between these molecules by V beta 3 and V beta 11.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436061 TI - Structure of hisactophilin is similar to interleukin-1 beta and fibroblast growth factor. AB - The fast reaction of the actin-based cytoskeleton in motile cells after stimulation with a chemoattractant requires a signal-transduction chain that creates a very specific environment at distinct regions beneath the plasma membrane. Dictyostelium hisactophilin, a unique actin-binding protein, is a submembranous pH sensor that signals slight changes of the H+ concentration to actin by inducing actin polymerization and binding to microfilaments only at pH values below seven. It has a relative molecular mass of 13.5K and its most unusual feature is the presence of 31 histidine residues among its total of 118 amino acids. The transduction of an external signal from the plasma membrane to the cytoskeleton is poorly understood. Here we report the protein's structure in solution determined by nuclear magnetic resonance spectroscopy. The nuclear Overhauser effect intensities of the three-dimensional nuclear Overhauser spectra were used directly in the calculations. The overall folding of histactophilin is similar to that of interleukin-1 beta and fibroblast growth factor, but the primary amino-acid sequence of hisactophilin is unrelated to these two proteins. PMID- 1436062 TI - Stable dye-DNA intercalation complexes as reagents for high-sensitivity fluorescence detection. AB - Fluorescent intercalation complexes of certain polycationic ligands with double stranded DNA provide a new class of multichromophore labels for fluorescence assays. PMID- 1436063 TI - Sex education and AIDS. PMID- 1436064 TI - Sex education and AIDS. PMID- 1436065 TI - The infectiousness of pompous prose. AB - For centuries, scientists have been bombarded with pleas for plain language. Why have these pleas had no effect, when the problem of unreadable prose could be solved at a stroke? PMID- 1436066 TI - Disease-of-the-month alive and well. PMID- 1436067 TI - Transcription. Riding high on the TATA box. PMID- 1436068 TI - Chemical ecology. Rubbish birds are poisonous. PMID- 1436069 TI - Coley's toxins. PMID- 1436070 TI - French modify polio plant in India. PMID- 1436071 TI - Stabilization of sea urchin flagellar microtubules by histone H1. AB - Complex microtubule assemblies are essential components of eukaryotic cilia and flagella. They are extremely stable and are not affected by agents that normally induce polymer disassembly. The molecular basis of this microtubular stability is unknown, and it is not related to any feature of the constitutive tubulin. In sea urchin sperm flagella, axonemal microtubules are found to be stabilized by a protein identical to histone H1, a result that defines a new role for this histone and provides evidence for a concerted evolution of chromatin and microtubular structures. PMID- 1436072 TI - Opponents of US earmarks propose reviews to temper worst elements of growing practice. PMID- 1436073 TI - Crystal structure of TFIID TATA-box binding protein. AB - The structure of a central component of the eukaryotic transcriptional apparatus, a TATA-box binding protein (TBP or TFIID tau) from Arabidopsis thaliana, has been determined by X-ray crystallography at 2.6 A resolution. This highly symmetric alpha/beta structure contains a new DNA-binding fold, resembling a molecular 'saddle' that sits astride the DNA. The DNA-binding surface is a curved, antiparallel beta-sheet. When bound to DNA, the convex surface of the saddle would be presented for interaction with other transcription initiation factors and regulatory proteins. PMID- 1436074 TI - US drug trials said to ignore gender differences. PMID- 1436075 TI - Absence of aluminium in neuritic plaque cores in Alzheimer's disease. AB - Controversy exists over whether aluminium has a role in the aetiology of Alzheimer's disease. Alzheimer's disease is neuropathologically characterized by the occurrence of a minimum density of neurofibrillary tangles and neuritic plaques in the hippocampus and the association cortex of the brain. The purported association of aluminium with Alzheimer's disease is based on: (1) the experimental induction of fibrillary changes in the neurons of animals by the injection of aluminium salts into brain tissue; (2) reported detection of aluminium in neuritic plaques and tangle-bearing neurons; (3) epidemiological studies linking aluminium levels in the environment, notably water supplies, with an increased prevalence of dementia; and (4) a reported decrease in the rate of disease progression following the administration of desferroxamine, an aluminium chelator, to clinically diagnosed sufferers of Alzheimer's disease. Here we use nuclear microscopy, a new analytical technique involving million-volt nuclear particles, to identify and analyse plaques in postmortem tissue from patients with Alzheimer's disease without using chemical staining techniques and fail to demonstrate the presence of aluminium in plaque cores in untreated tissue. PMID- 1436076 TI - Real and optimal neural images in early vision. AB - It has been suggested that the first steps in visual processing strive to compress as much information as possible about the outside world into the limited dynamic range of the visual channels. Here I compare measured neural images with theoretical calculations based on maximizing information, taking into account the statistical structure of natural images. Neural images were obtained by scanning an image while recording from a second-order neuron in the fly visual system. Over a 5.5-log-units-wide range of mean intensities, experiment and theory correspond well. At high mean intensities, redundancy in the image is reduced by spatial and temporal antagonism. At low mean intensities, spatial and temporal low-pass filtering combat noise and increase signal reliability. PMID- 1436077 TI - New biology institute in Milan prizes quality above loyalty in effort to become world-class. PMID- 1436078 TI - Preserved figure-ground segregation and symmetry perception in visual neglect. AB - A central controversy in current research on visual attention is whether figures are segregated from their background preattentively, or whether attention is first directed to unstructured regions of the image. Here we present neurological evidence for the former view from studies of a brain-injured patient with visual neglect. His attentional impairment arises after normal segmentation of the image into figures and background has taken place. Our results indicate that information which is neglected and unavailable to higher levels of visual processing can nevertheless be processed by earlier stages in the visual system concerned with segmentation. PMID- 1436079 TI - NIH plans trials of controversial AIDS drug. PMID- 1436080 TI - A new tropomyosin essential for cytokinesis in the fission yeast S. pombe. AB - Mutations in the Schizosaccharomyces pombe cdc8 gene impair cytokinesis. Here we clone cdc8+ and find that it encodes a novel tropomyosin. Gene disruption results in lethal arrest of the cell cycle, but spore germination, cell growth, DNA replication and mitosis are all unaffected. Haploid cdc8 gene disruptants are rescued by expression of a fibroblast tropomyosin complementary DNA. Immunofluorescence microscopy of wild type and cdc8 gene disruptants indicates that cdc8 tropomyosin is present in two distinct cellular distributions: in dispersed patches, and during cytokinesis as a transient medial band. Collectively these results indicate that cdc8 tropomyosin has a specialized role which, we suggest, is to form part of the F-actin contractile ring at cytokinesis. These results establish the basis for further genetic studies of cytokinesis and of contractile protein function in S. pombe. PMID- 1436081 TI - Zebrafish pax[b] is involved in the formation of the midbrain-hindbrain boundary. AB - Among the genes thought to be involved in patterning the nervous system are a family of developmentally regulated paired box-containing (Pax) genes. Mutations in some of these Pax genes lead to severe developmental abnormalities. Zebrafish pax[b](pax[zf-b]) is a member of the Pax gene family that is expressed in the presumptive posterior midbrain from the end of gastrulation and, at later stages, in other localized regions of the developing embryo. Here we show that injection of antibodies raised against the pax[b] protein causes a localized malformation at the midbrain-hindbrain boundary. In situ hybridizations demonstrate that antibody injection causes downregulation of pax[b] transcripts in the posterior midbrain and alteration of wnt-1 and eng-2 expression in this area. The data demonstrate an involvement of pax[b] in the formation of the midbrain-hindbrain junction. PMID- 1436082 TI - Coping with toxic pulses. PMID- 1436083 TI - Message in a bottle. AB - Insights from the classic work of Luria and Delbruck on bacterial mutation rates may be applied to tracking human gene defects prevalent in isolated populations. PMID- 1436084 TI - Too many reviews? PMID- 1436085 TI - Neural networks. Stitch in time saves design. PMID- 1436086 TI - Veterinary medicine. Molecular genetics arrives on the farm. PMID- 1436087 TI - Thyroid cancer incidence. PMID- 1436088 TI - Ice-crystal growth and lectins. PMID- 1436089 TI - Eradication of rabies in Europe. PMID- 1436090 TI - Structure of a C-type mannose-binding protein complexed with an oligosaccharide. AB - C-type (Ca(2+)-dependent) animal lectins such as mannose-binding proteins mediate many cell-surface carbohydrate-recognition events. The crystal structure at 1.7 A resolution of the carbohydrate-recognition domain of rat mannose-binding protein complexed with an oligomannose asparaginyl-oligosaccharide reveals that Ca2+ forms coordination bonds with the carbohydrate ligand. Carbohydrate specificity is determined by a network of coordination and hydrogen bonds that stabilizes the ternary complex of protein, Ca2+ and sugar. Two branches of the oligosaccharide crosslink neighbouring carbohydrate-recognition domains in the crystal, enabling multivalent binding to a single oligosaccharide chain to be visualized directly. PMID- 1436091 TI - Motor learning in a recurrent network model based on the vestibulo-ocular reflex. AB - Most models of neural networks have assumed that neurons process information on a timescale of milliseconds and that the long-term modification of synaptic strengths underlies learning and memory. But neurons also have cellular mechanisms that operate on a timescale of tens or hundreds of milliseconds, such as a gradual rise in firing rate in response to injection of constant current or a rapid rise followed by a slower adaptation. These dynamic properties of neuronal responses are mediated by ion channels that are subject to modulation. We demonstrate here how a neural network with recurrent feedback connections can convert long-term modulation of neural responses that occur over these intermediate timescales into changes in the amplitude of the steady output from the system. This general principle may be relevant to many feedback systems in the brain. Here it is applied to the vestibulo-ocular reflex, whose amplitude is subject to long-term adaptive modification by visual inputs. The model reconciles apparently contradictory data on the neural locus of the cellular mechanisms that mediate this simple form of learning and memory. PMID- 1436092 TI - A single amino-acid difference confers major pharmacological variation between human and rodent 5-HT1B receptors. AB - Neuropsychiatric disorders such as anxiety, depression, migraine, vasospasm and epilepsy may involve different subtypes of the 5-hydroxytryptamine (5-HT) receptor. The 1B subtype, which has a unique pharmacology, was first identified in rodent brain. But a similar receptor could not be detected in human brain, suggesting the absence in man of a receptor with equivalent function. Recently a human receptor gene was isolated (designated 5-HT1B receptor, 5-HT1D beta receptor, or S12 receptor) which shares 93% identity of the deduced protein sequence with rodent 5-HT1B receptors. Although this receptor is identical to rodent 5-HT1B receptors in binding to 5-HT, it differs profoundly in binding to many drugs. Here we show that replacement of a single amino acid in the human receptor (threonine at residue 355) with a corresponding asparagine found in rodent 5-HT1B receptors renders the pharmacology of the receptors essentially identical. This demonstrates that the human gene does indeed encode a 1B receptor, which is likely to have the same biological functions as the rodent 5 HT1B receptor. In addition, these findings show that minute sequence differences between homologues of the same receptor from different species can cause large pharmacological variation. Thus, drug-receptor interactions should not be extrapolated from animal to human species without verification. PMID- 1436093 TI - Cell-free expression of functional Shaker potassium channels. AB - The functional activity of ion channels and other membrane proteins requires that the proteins be correctly assembled in a transmembrane configuration. Thus, the functional expression of ion channels, neurotransmitter receptors and complex membrane-limited signalling mechanisms from complementary DNA has required the injection of messenger RNA or transfection of DNA into Xenopus oocytes or other target cells that are capable of processing newly translated protein into the surface membrane. These approaches, combined with voltage-clamp analysis of ion channel currents, have been especially powerful in the identification of structure-function relationships in ion channels. But oocytes express endogenous ion channels, neurotransmitter receptors and receptor-channel subunits, complicating the interpretation of results in mRNA-injected eggs. Furthermore, it is difficult to control experimentally the membrane lipids and post-translational modifications that underlie the regulation and modulation of ion channels in intact cells. A cell-free system for ion channel expression is ideal for good experimental control of protein expression and modulatory processes. Here we combine cell-free protein translation, microsomal membrane processing of nascent channel proteins, and reconstitution of newly synthesized ion channels into planar lipid bilayers to synthesize, glycosylate, process into membranes, and record in vitro the activity of functional Shaker potassium channels. PMID- 1436094 TI - Proteasome subunits encoded in the MHC are not generally required for the processing of peptides bound by MHC class I molecules. AB - Antigen processing provides major histocompatibility complex (MHC) class I molecules with short peptides, which they selectively bind and present to cytotoxic T lymphocytes. The proteolytic system generating these peptides in the cytosol is unidentified, but their delivery into the endoplasmic reticulum is mediated by the TAP1-TAP2 transporter encoded in the MHC class II region. Closely linked to TAP1 and TAP2 are genes for the LMP2 and LMP7 proteins, which resemble components of proteasomes, proteolytic complexes known to degrade cytosolic proteins. This association has led to the common assumption that proteasomes function in this immunological pathway (discussed in ref. 15). We now show that the expression of stably assembled class I molecules and apparently normal peptide processing can be completely restored in the absence of LMP2 and LMP7 in the human lymphoblastoid cell line mutant 721.174 (refs 16, 17). The identity of LMP7 is directly confirmed by reconstitution of a proteasomal subunit after gene transfer. These results therefore dispute the hypothetical involvement of proteasomes in antigen processing, although a more subtle effect of LMP2 and LMP7 cannot be ruled out. PMID- 1436095 TI - Abrogation by c-myc of G1 phase arrest induced by RB protein but not by p53. AB - Inactivating mutations of the retinoblastoma gene (RB) are found in a wide variety of tumour cells. Replacement of wild-type RB can suppress the tumorigenicity of some of these cells, suggesting that the RB protein (Rb) may negatively regulate cell growth. As activation of c-myc expression promotes cell proliferation and blocks differentiation, it may positively regulate cell growth. The c-myc protein is localized in the nucleus and can physically associate with RB protein in vitro, hence c-myc may functionally antagonize RB function. Microinjection of Rb in G1 phase reversibly arrests cell-cycle progression. Here we co-inject RB protein with c-myc, EJ-ras, c-fos or c-jun protein. Co-injection of c-myc, but not EJ-ras, c-fos or c-jun, inhibits the ability of Rb to arrest the cell cycle. The c-myc does not inhibit the activity of another tumour supressor, p53 (ref. 12). Thus, c-myc and RB specifically antagonize one another in the cell. PMID- 1436096 TI - Actin cables and epidermal movement in embryonic wound healing. AB - Skin wounds in embryos heal rapidly and perfectly. Even though the epidermis appears to be stretched taut over the surface of a structure such as a growing limb bud, its response to wounding is to close over the lesion, rather than to gape more widely. In adult wounds, the epidermis seems to migrate by means of lamellipodia, crawling over the exposed connective tissue. But in embryonic wounds we do not see lamellipodia. The epidermis at the edge of the wound looks smooth, as though under a circumferential tension. Here we show that a cable of filamentous actin appears to run continuously around most of the wound margin. It is confined to the single row of basal cells at the free edge of the epidermis. We suggest that the actin cable acts as a contractile 'purse string' to close up the embryonic wound. PMID- 1436098 TI - Clinton on science. PMID- 1436097 TI - Detection of human DNA-carcinogen adducts. PMID- 1436099 TI - Researchers recommend US AIDS vaccine trials. PMID- 1436100 TI - French blood contamination. PMID- 1436101 TI - Biotechnology soared and fell in a roller-coaster 12 months. PMID- 1436102 TI - Hunterian Institute. PMID- 1436103 TI - Women in science. PMID- 1436104 TI - Conflicts of interest declared. PMID- 1436105 TI - Epidemiology. Molecular potential. PMID- 1436106 TI - Molecular and genetic damage in humans from environmental pollution in Poland. AB - Extreme environmental pollution such as that found in the highly industrialized Silesian region of Poland has been associated with increased risk of cancer and adverse reproductive outcomes. Among the most prevalent carcinogenic and mutagenic air pollutants in Silesia are the polycyclic aromatic hydrocarbons (PAH) which are largely produced by industrial and residential combustion of coal. Molecular epidemiology aims to prevent disease by using biological markers to identify risks well before clinical onset to allow effective intervention. Here, we use a battery of biological markers to measure molecular and genetic damage in peripheral blood samples from residents of Silesia and from persons living in a rural, less polluted area of Poland. The results show that their exposure to environmental pollution is associated with significant increases in carcinogen-DNA adducts (PAH-DNA and aromatic adducts), in sister chromatid exchange including high-frequency cells, and in chromosomal aberrations as well as a doubling in the frequency of ras oncogene overexpression. We found that aromatic adducts on DNA were significantly correlated with chromosomal mutation, providing us with a molecular link between environmental exposure and a genetic alteration relevant to cancer and reproductive risk. PMID- 1436107 TI - Enhancing protein C interaction with thrombin results in a clot-activated anticoagulant. AB - Human protein C is a vitamin K-dependent plasma glycoprotein that circulates as an inactive zymogen. At the endothelial cell surface, thrombin in complex with the integral membrane protein thrombomodulin converts protein C to its active form by specific cleavage of an activation peptide. The activated form of protein C has potent anticoagulant activity as a feedback regulator of thrombin generation (reviewed in refs 4-6), and also has profibrinolytic, anti-ischaemic and anti-inflammatory properties. Protein C is effective in the treatment of model and human thrombotic diseases but, except when it has been used to treat genetic or acquired deficiencies and microvascular thrombosis, it is administered as the activated enzyme, which has a short biological half-life. We have altered two putative inhibitory acidic residues near the thrombin cleavage site, which results in a 30-fold increase in substrate utilization by alpha-thrombin. We combined these changes with a genetically altered glycoform to generate a zymogen protein C with a 60-fold increased cleavage rate by free alpha-thrombin, independent of its cofactor thrombomodulin. We show that this 'proform' of protein C, unlike the natural circulating zymogen, can be activated by thrombin generated in clotting human plasma, resulting in an inhibition of further clot formation. Our data therefore show that we have engineered a site-activated agent, which only has anticoagulant activity when significant amounts of thrombin are being generated. PMID- 1436108 TI - Lifespan of human lymphocyte subsets defined by CD45 isoforms. AB - The lifespan of thymic-derived or T lymphocytes is of particular interest because of their central role in immunological memory. Is the recall of a vaccination or early infection, which may be demonstrated clinically up to 50 years after antigen exposure, retained by a long-lived cell, or by its progeny? Using the observation that T lymphocyte expression of isoforms of CD45 corresponds with their ability to respond to recall antigens, we have investigated the lifespan of both CD45R0 (the subset containing responders, or 'memory' cells) and CD45RA (the unresponsive, or 'naive' subset) lymphocytes in a group of patients after radiotherapy. Here we report rapid loss of unstable chromosomes from the CD45R0 but not the CD45RA pool. Immunological memory therefore apparently resides in a population with a more rapid rate of division. Differing survival curves for the two subsets are best described by a model in which there is also reversion in vivo from the CD45R0 to the CD45RA phenotype. Expression of CD45R0 in T cells may therefore be reversible. PMID- 1436109 TI - Rat liver protein linking chemical and immunological detoxification systems. AB - Mammals have separate enzymatic and cellularly mediated detoxification systems. Glutathione S-transferases (GSTs) protect against xenobiotic chemicals which continuously enter the body, largely through mucous membranes. These enzymes catalyse the conjugation of glutathione with a wide variety of electrophilic compounds rendering them non-toxic. Mammals also mount a cellular immunological response on entry of foreign cells, viruses or macromolecules into the body. T lymphocytes mobilize at the site of foreign body entry and secrete protein messengers called lymphokines. Secondary to T lymphocytes, macrophages concentrate at the infection site and function in antigen processing and phagocytosis. In vitro, macrophage movement is arrested by one class of lymphokines known as macrophage migration inhibitory factors (MIFs). We report here the purification of milligram quantities of a unique multifunctional protein from rat liver which links enzymatic and immunological detoxification systems. This protein actuates both GST and MIF activity and matches the primary structure of a human MIF in 25 out of 26 amino-terminal amino acids. Primary structure comparisons revealed significant similarity between GSTs and MIF. The glutathione affinity chromatography purification described here yields a 100-fold increase in obtaining MIF and will aid understanding of its precise biological function. PMID- 1436110 TI - NMR study of parallel-stranded tetraplex formation by the hexadeoxynucleotide d(TG4T). AB - Multistranded DNA structures based upon guanine association have been proposed to be important in the structure of chromosome telomeres and in immunoglobulin class switching. Nucleic acids containing runs of guanine bases form a number of structures in vitro, including fold-back structures (Fig. 1a) and parallel stranded quadruplex structures in DNA and RNA. The features of fold-back structures have now been determined at high-resolution. The different structures are probably based on a tetrad of hydrogen-bonded guanine bases (Fig. 1b), with buffer conditions and sequence effects mediating isomerization between the different forms. Here we use NMR spectroscopy to investigate the solution structure of the complex formed by the hexadeoxynucleotide d(TG4T) in the presence of sodium ions. We have observed the formation of a parallel-stranded quadruplex containing hydrogen-bonded tetrads of guanine. The parallel-stranded form differs significantly from the fold-back form, with individual nucleotide conformations being closer to those of B-form DNA. PMID- 1436111 TI - The antiglucocorticoid RU 38486 reverses the wasting syndrome in newborn rats. PMID- 1436113 TI - A universal constant in temporal segmentation of human speech. A reply to Schleidt and Feldhutter (1989). PMID- 1436112 TI - Seasonal changes in adult mammalian brain weight. PMID- 1436114 TI - [Modeling in biology. Structured analysis of intracellular calcium oscillations in electrically non-excitable cells]. AB - In this paper a systematic approach to the mathematical modeling of intracellular Ca2+ oscillations is introduced. After a structured analysis a stochastic model of the system is derived which is numerically tractable by means of a stochastic simulation. A critical discussion of theoretical models for Ca2+ oscillations reveals that not all of the proposed mechanisms are consistent with experimental data. In addition, a model for oscillatory calcium waves is presented. Uncovering these mechanisms facilitates the design of anti-mitotic drugs interfering with Ca2+ metabolism. PMID- 1436115 TI - [The phenomenon of hearing: an interdisciplinary discourse. I]. AB - For the last century hearing has been considered a purely passive process. G. S. Ohm's and H. v. Helmholtz's resonance theory of hearing was widely accepted until Wien's fundamental objection led to G. v. Bekesy's and O. F. Ranke's travelling wave theory, the hydrodynamics of the inner ear that distributes the frequencies along the basilar membrane, which acts as the "first filter". Seebeck, Licklider, Schouten, and deBoer emphasized also the time domain and developed the concept of periodicity hearing and the "residue phenomenon". However, it was not until the concept of the "cochlear amplifier" and "active hearing" with energy generation during the transduction process within the ear itself was introduced that the "second filter" could be understood. Kemp's echo was the key to this revolutionary step in the theory of hearing. PMID- 1436116 TI - Isolation of the first crystalline D-penicillamine complex of iron and some remarks on relevant aspects of metal-chelating drugs as well as metabolism disorders. PMID- 1436117 TI - Transient increase in membrane permeability of L1210 cells upon exposure to lithotripter shock waves in vitro. PMID- 1436118 TI - Comparison of erythrocyte insulin receptors in different species of vertebrates. PMID- 1436119 TI - High-frequency two-tone distortions from the ear of the mustached bat, Pteronotus parnellii reflect enhanced cochlear tuning. PMID- 1436120 TI - Stimulus-dependent oscillatory activity in the lateral geniculate body of the cat. PMID- 1436121 TI - Differential coupling of 5-HT1A receptors occupied by 5-HT or 8-OH-DPAT to adenylyl cyclase. AB - Human serotonin (5-hydroxytryptamine, 5-HT)-1A receptors have been transfected in NIH-3T3 cells, and their coupling to adenylyl cyclase was analysed depending on 1) the number of receptor expressed, 2) the experimental conditions used, 3) the nature of the agonists. Two monoclonal cell lines were used, expressing low (45 fmol/mg) and high (500 fmol/mg) levels of 5-HT1A receptor. Two methods were tested to study the negative coupling of the transfected 5-HT1A receptors to adenylyl cyclase: 1) measurement of cAMP production in intact cells, 2) measurement of adenylyl cyclase activity in vitro on membrane preparations. Studies on intact cells revealed that an increase in the receptor concentration was followed by 1) an increase in the efficacies of 5-HT, 5-CT (5 carboxamidotryptamine) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 2) a 2 to 3-fold increase in the potency of 5-CT and 8-OH-DPAT, but no change in the potency of 5-HT. In membrane preparations, 8-OH-DPAT dose-response curve was shifted leftwards when the receptor concentration became higher whereas the corresponding shift was smaller for 5-HT and absent for 5-CT. Surprisingly, on membrane preparations, 8-OH-DPAT was a partial agonist relative to 5-HT. The relative efficacy of 8-OH-DPAT was lower in the clone expressing the lowest level of receptor. This partial agonist behavior of 8-OH-DPAT could be modulated by the ionic conditions under which the adenylyl cyclase activity was measured.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436122 TI - Inhibitory and excitatory muscarinic receptors modulating the release of acetylcholine from the postganglionic parasympathetic neuron of the chicken heart. AB - The effects of muscarinic receptor antagonists on ACh release were studied in the absence or presence of cholinesterase (ChE) inhibition using the isolated perfused chicken heart. Presynaptic inhibitory muscarinic autoreceptor were characterized by determining the potency of various antagonists to enhance [3H] ACh release evoked by field stimulation (3 Hz, 1 min). The order of potencies was: (+/-)-telenzepine > atropine > 4-DAMP > silahexocyclium > pirenzepine > hexahydro-siladifenid-ol > AF-DX 116. The comparison with known pA2 values for M1 , M2- and M3-receptors revealed that the presynaptic autoreceptor meets the criteria of an M1-receptor. Basal, not electrically evoked overflow of unlabelled ACh into the perfusate was caused by 'leakage' release (non-exocytotic), as it was independent of extracellular Ca2+. Muscarinic receptor antagonists failed to enhance basel overflow. In contrast, when ChE activity was inhibited by 10(-6) M tacrine or pretreatment with 10(-4) M DFP, the ACh overflow was partially Ca(2+) dependent and was reduced by tetrodotoxine. Moreover, block of the inhibitory muscarinic autoreceptors by (+/-)-telenzepine or pirenzepine caused a several fold enhancement of the ACh release. The potencies of these antagonists were identical to those found for the electrically evoked [3H]-ACh release. The rate of ACh release enhanced by ChE inhibition plus telenzepine corresponds to about 12% of the total ACh pool per min, which is about the maximum amount of ACh that is available for any kind of stimuli. The release was dependent on the presence of exogenous choline. Hence elevation of ACh release led to a correspondingly enhanced ACh synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436124 TI - Evidence for M1 muscarinic cholinoceptors mediating facilitation of noradrenaline release in guinea-pig carotid artery. AB - The muscarinic agonists acetylcholine (1-50 mumol/l), carbachol (1-10 mumol/l) and McN-A-343 (1-50 mumol/l, selective for M1 receptors) increased, in a concentration-dependent manner, the electrically-evoked tritium overflow from guinea-pig carotid arteries preincubated with [3H]-noradrenaline. The increase caused by acetylcholine was not modified by hexamethonium (300 mumol/l) but was reduced by the muscarinic receptor antagonists methylatropinium (0.5 and 1 nmol/l, non-selective), pirenzepine (1 and 5 nmol/l, M1-selective), methoctramine (1 and 5 mumol/l, M2-selective) and p-fluoro-hexahydro-sila-difenidol (0.1-1 mumol/l, M3-selective). The order of potencies (expressed as negative logarithms of concentrations that reduced by 50% the facilitatory effect of acetylcholine) was: methyl-atropinium (9.93) > pirenzepine (8.83) > p-fluoro-hexahydro siladifenidol (6.81) > or = methoctramine (6.20). These results demonstrate the existence of facilitatory M1 receptors modulating noradrenaline release in blood vessels. PMID- 1436123 TI - Quest for agonist and antagonist selectivity at muscarinic receptors in guinea pig smooth muscles and cardiac atria. AB - Potencies of 11 muscarinic agonists in eliciting contraction of smooth muscle in guinea-pig ileum, trachea, urinary bladder and uterus and in inhibiting the rate of contractions of cardiac atria were compared. While acetylcholine (ACh) was the most potent agonist on the ileum, uterus and cardiac atria, cis-L(+)-dioxolane was equally as potent as ACh on the ileum and more potent on the urinary bladder and trachea. Compared to ACh, methylfurmethide, oxotremorine, acetoxybut-2-inyl trimethylammonium and cis-L(+)-dioxolane acted weakly on the atria. Aceclidine, arecoline and acetyl-beta-methylcholine displayed selectivity for the urinary bladder and pilocarpine for the tracheal and urinary bladder smooth muscles. Oxotremorine had very low activity on the uterus. The stereoselectivity of muscarinic ACh receptors (mAChRs) for cis-L(+)-and cis-D(-)-dioxolane was low in the urinary bladder and uterus and high in the ileum and trachea. Most antagonists showed little selectivity between different organs, but S(-) phenylcyclohexylglycoloyl choline was 6 times more active on the urinary bladder than on the ileum and AF-DX 116 was 12-30 times more active on the atria than on the smooth muscles. Among the N-alkyl derivatives of benzilylcholine, the octyl derivative as 400 times more active on the ileum than on the atria, while among the N-alkyl derivatives of QNB, the N-decyl derivative was 41 times more active on the ileum. The observed differences in the potency of various agonists and their stereoisomers on different smooth muscles cannot be explained by differences in the accessibility of receptors or in receptor reserve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436125 TI - Nicotinic and muscarinic components of rat brain dopamine synthesis stimulation induced by physostigmine. AB - The role of a putative cholinergic control of ascending midbrain dopamine neurons was studied with biochemical methods in the unanaesthetized male albino rat. Post mortem catechols were measured with high performance liquid chromatography with electrochemical detection. The acetylcholinesterase inhibitor physostigmine (0.5 mg/kg s.c.) enhanced L-dihydroxyphenylalanine (DOPA) and 3,4 dihydroxyphenylacetic acid (DOPAC) levels in both the corpus striatum and limbic areas (nucleus accumbens) after inhibition of aromatic amino acid decarboxylase with NSD-1015, indicating an enhanced synthesis of dopamine in these brain regions. The effect of physostigmine was blocked both in the corpus striatum and in limbic areas by the centrally penetrating muscarinic antagonist scopolamine (1.0 mg/kg s.c.). In contrast, the nicotinic antagonist mecamylamine (1.0 mg/kg s.c.) significantly reduced the stimulatory effect of physostigmine in limbic areas, but not in the corpus striatum. The present results suggest that ascending dopamine neurons are influenced by cholinergic synaptic transmission being mediated mainly by muscarinic receptors as regards the nigrostriatal system, and by both nicotinic and muscarinic receptors as regards the mesolimbic system. The nicotinic influence appears to primarily control phasic activity of the dopamine neurons. PMID- 1436126 TI - Effect of ageing on the number of neuronal noradrenaline uptake sites in the rat vas deferens. AB - Previous work has shown an age-related reduction in neuronal uptake of noradrenaline in the prostatic, but not in the epididymal portion of the rat vas deferens. In the present paper, the influence of ageing on the number of [3H]desipramine binding sites and on the effect of lithium on neuronal [3H]noradrenaline uptake were studied in the prostatic and epididymal portions of vasa deferentia from 4- and 20-month-old rats. The affinity for [3H]desipramine (Kd values) in the epididymal and prostatic portions did not change with age. However, ageing reduced the maximal number of [3H]desipramine binding sites (Bmax values) in the prostatic, but not in the epididymal portion. Lithium potentiated neuronal [3H]noradrenaline uptake only in the prostatic portion and this potentiation was not changed by ageing. The results showed differences in neuronal noradrenaline uptake between the two portions of the vas deferens. Furthermore, the data suggest that the age-related reduction in neuronal uptake in the prostatic portion is due to a reduction in the number of neuronal uptake sites for noradrenaline. PMID- 1436127 TI - Changes in cholecystokinin receptor binding in rat brain after selective damage of locus coeruleus projections by DSP-4 treatment. AB - Brain cholecystokinin (CCK)- and noradrenergic activities are two neurochemical systems implicated in anxiety and deficits in novelty-related behaviour. In order to clarify a possible interaction between CCK- and noradrenergic neurotransmission in the brain, DSP-4 [N-(2-chloroethyl)-N-ethyl-2 bromobenzylamine], a neurotoxin that selectively destroys noradrenaline containing nerve terminals originating from the locus coeruleus, was administered to rats IP (10 and 50 mg/kg) seven days before decapitation. Noradrenaline uptake was very markedly reduced in the frontal cortex and hippocampus of the DSP-4 treated animals, whereas the decrease in the hypothalamus was smaller but still statistically significant. Dopamine uptake in the corpus striatum, as well as serotonin uptake in the frontal cortex, hippocampus and hypothalamus, were not influenced by DSP-4 treatment. Concomitantly, CCK receptor binding in certain brain regions was markedly affected. Thus, CCK receptor density was significantly higher in the frontal cortex and hippocampus of DSP-4-treated rats. If desipramine (25 mg/kg) was administered before DSP-4 treatment, the DSP-4-induced changes both in noradrenaline uptake and CCK receptor binding were not present, suggesting that both effects were exerted after uptake of the neurotoxin by the nerve terminals. The time-course of the development of changes in CCK-8 binding paralleled with some lag the development of changes in noradrenaline uptake. These findings demonstrate the denervation of noradrenergic input from the locus coeruleus induces certain alterations in the CCKergic neurotransmission. These alterations are similar to those seen in rats with deficits in response to novel stimuli, and may therefore mediate the neophobic responses observed in animals after lesions of noradrenergic innervation of the forebrain. PMID- 1436128 TI - Alcohol withdrawal reaction as a result of adaptive changes of excitatory amino acid receptors. AB - Recent electrophysiological and biochemical studies suggest that ethanol interferes with excitatory amino acid (EAA) neurotransmission. Here, we present electrophysiological evidence that, following cessation of a chronic ethanol treatment, noradrenergic locus coeruleus (LC) neurons display hyperactivity at the same time as a specifically enhanced sensitivity to microiontophoretically applied NMDA or quisqualate. Furthermore, after chronic ethanol treatment, but not before, the NMDA receptor antagonist MK 801 (0.3-2.4 mg/kg, i.v.) dose dependently inhibited the firing of the LC neurons. Our data indicate that an up regulation of EAA receptors located on LC neurons accounts for the changes in LC firing in ethanol-treated rats. We propose that activation of the LC contributes to the clinical signs of the ethanol abstinence reaction and that EAA antagonists may be beneficial therapeutically for its treatment. PMID- 1436129 TI - Studies on the effect of two angiotensin-converting enzyme inhibitors, captopril and cilazapril, on platelet and vascular prostaglandin metabolism in vivo. AB - We have studied in 12 healthy volunteers the effects of two angiotensin converting enzyme (ACE) inhibitors, captopril and cilazapril, on vascular and platelet prostaglandin metabolism, in a double-blind, placebo-controlled, randomized cross-over study. Formation of 6-keto-prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TxB2) was measured locally at the site of a microvascular injury. Similar amounts of TxB2 and 6-keto-PGF1 alpha were generated following administration of either ACE inhibitor as compared to placebo. It is concluded that neither captopril nor cilazapril significantly influence vascular and platelet prostaglandin metabolism. PMID- 1436130 TI - Evaluation of the effects of felodipine, verapamil and hydralazine on the survival rate of rats subjected to lethal effects of oxygen free radicals. AB - Intravenous administration of xanthine (X: 0.225 mg/kg, i.v.) plus xanthine oxidase (XO: 3.0 units/kg, i.v.) to anesthetized rats resulted in a rapid fall in the arterial pressure and a mortality rate of over 80% during 120 min observation period. Pretreatment of the rats with superoxide dismutase (SOD) or SOD plus catalase significantly enhanced survival rate to 60% confirming that the toxicity after [X + XO] administration is due to the generation of oxygen free radicals. Pretreatment of the rats with either felodipine, a dihydropyridine calcium antagonist or verapamil, a structurally different Ca(2+)-channel blocker was most effective in promoting survival rate to 90%; in contrast, hydralazine, an arteriolar dilator but not a calcium antagonist, was ineffective in significantly enhancing survival. In the vehicle treated groups, mortality of the rats after [X + XO] administration was associated with significant increases in serum creatine phosphokinase (CPK) levels; both the calcium antagonists as well as hydralazine prevented any significant changes in CPK levels. Since only the calcium antagonists but not hydralazine were effective in providing significant protection against mortality, the data suggests that CPK may not be a reliable indicator to predict prevention of lethal toxicity induced by free radicals. Hence, the observation that calcium antagonists can promote survival would suggest that calcium overload may be the ultimate mediator of tissue toxicity. These observations can account for the remarkable efficacy of various calcium antagonists in preventing ischemia-reperfusion induced damage to organs, such as heart and kidneys, in which a role for free radicals has been postulated. PMID- 1436132 TI - Feeding but not salt loading is the dominant factor controlling urinary dopamine excretion in conscious rats. AB - We studied urinary dopamine excretion in three different groups of rats after the following treatment regimens: normal chow and tap water (controls, CON), normal chow and 1% NaCl as drinking water (high salt, HS), and chow with low sodium content plus tap water (low salt, LS). On days 5 and 7 of the respective dietary treatment, rats were placed in metabolic cages. Using a cross over design, chow was given (fed) or withheld (fasted). Urine was collected for 24 h and analyzed for sodium, creatinine, and dopamine. Urinary dopamine excretion did not change in proportion to large differences in sodium excretion in fasted animals. Sodium excretion was enhanced (45%) due to feeding only in the CON group but not in HS and LS rats. However, there was a striking increase in renal dopamine excretion in fed compared to fasted animals, irrespective of their sodium diet: 2.5-fold in CON, 2-fold in HS, and 1.8-fold in LS rats. Urinary creatinine excretion was significantly elevated during the feeding condition compared to fasted animals in all treatment groups. Our results demonstrate that urinary dopamine excretion is dominantly influenced by feeding but not by oral sodium intake in conscious rats. We conclude that 1) the dietary state of the animals should be controlled in experiments on renal dopamine production, 2) renally formed dopamine could be involved in the functional response of the kidney to oral food intake. PMID- 1436131 TI - The relaxant effects of cromakalim (BRL 34915) on human isolated airway smooth muscle. AB - Cromakalim (BRL 34915) is a potassium channel opener with therapeutic potential as a bronchodilator in asthma. Cromakalim (0.1-30 mumol/l) inhibited the spontaneous tone of human isolated bronchi in a concentration-related manner being nearly as effective as isoprenaline or theophylline. The order of relaxant potencies (expressed as -log10 IC50 mol/l; mean +/- SEM) was isoprenaline (7.29 +/- 0.27; n = 8) > cromakalim (5.89 +/- 0.12; n = 7) > theophylline (4.07 +/- 0.13; n = 10). In human bronchi where tone had been raised by addition of histamine (0.1 mmol/l), acetylcholine (0.1 mmol/l) or leukotriene D4 (LTD4, 0.1 mumol/l), the relaxant effect of cromakalim was substantially reduced. Cromakalim suppressed the contraction produced by KCl (25 mmol/l) but not that produced by KCl (120 mmol/l). Tetraethylammonium (8 mmol/l) was without effect against the relaxant action of cromakalim but procaine (0.5-5 mmol/l) and glibenclamide (0.3 mumol/l) antagonised it. Cromakalim (10 mumol/l) produced an upward displacement of concentration-effect curves for KCl (1-100 mmol/l), acetylcholine (1 nmol/l-1 mmol/l) and histamine (1 nmol/l-1 mmol/l) but it did not alter the concentration effect curve for LTD4 (0.1 nmol/l-0.1 mumol/l). When tissues were challenged in the presence of cromakalim (10 mumol/l) with KCl (100 mmol/l), acetylcholine (1 mmol/l) or histamine (1 mmol/l), an enhanced contraction was observed compared to control tissues. This enhancement by cromakalim was absent when tissues were challenged with acetylcholine or histamine in either a Ca(2+)-free medium (plus EGTA 0.1 mmol/l) or in the presence of verapamil (10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436134 TI - Focus on smokeless tobacco. PMID- 1436133 TI - Depression by neuropeptide Y of noradrenergic inhibitory postsynaptic potentials of locus coeruleus neurones. AB - Intracellular recordings were performed in a pontine slice preparation of the rat brain containing the locus coeruleus (LC). The spontaneous firing of action potentials was prevented by passing continuous hyperpolarizing current via the recording electrode. Focal electrical stimulation evoked a synaptic depolarization (PSP) followed by a hyperpolarization (IPSP). Neuropeptide Y (NPY; 0.1 mumol/l) inhibited the IPSP only. Pressure ejection of noradrenaline produced hyperpolarization which was potentiated in the presence of NPY (0.1 mumol/l). Hence, NPY appears to inhibit the release of noradrenaline from dendrites or recurrent axon collaterals of LC neurones. PMID- 1436135 TI - HIV-infected pediatric patients. PMID- 1436136 TI - The content of one doctor's practice. Preserving the biopsychosocial model. PMID- 1436137 TI - The content of one doctor's practice. The patient as the focus of the practice of medicine. PMID- 1436138 TI - The content of one doctor's practice. The importance of being an artist. PMID- 1436139 TI - The content of one doctor's practice. My clinical odyssey. PMID- 1436140 TI - A response to: "A woman with too much facial hair". PMID- 1436141 TI - Responses to: "Youth and tobacco". RJR's medical director and two family physicians discuss the issue of smoking among youth. PMID- 1436142 TI - Youth and tobacco. PMID- 1436144 TI - Politics and medicine. Interview by Edward C. Halperin. PMID- 1436143 TI - Was Hercules a stable person? Astemizole overdose. PMID- 1436145 TI - Outcome at one year in infants with chronic lung disease receiving comprehensive follow-up care. A regional experience in North Carolina, 1984-1990. PMID- 1436146 TI - Cushing's disease. PMID- 1436147 TI - Adrenal insufficiency after removal of an apparently non-functional adrenal mass. Cushing's diathesis without Cushing's syndrome. PMID- 1436148 TI - Pneumonia vaccine reaction. PMID- 1436149 TI - Microsurgical reversal of female sterilization. A community hospital experience. PMID- 1436150 TI - Enhancing adherence with mammography through patient letters and physician prompts. A pilot study. PMID- 1436151 TI - Mediation of medical malpractice claims. PMID- 1436152 TI - Prudent prescribing. Prescribing suggestions for physicians. AB - "A significant problem facing patients throughout the country is the rising cost of medical care. In addition to the physician's fees and laboratory charges of a routine office visit, patients may face an even greater bill from the pharmacy. There are several ways that physicians can help." PMID- 1436153 TI - Prescription medicines: did you know...? PMID- 1436154 TI - Successful laparoscopic management of perforated gallbladder associated with Salmonella javiana infection. PMID- 1436155 TI - The Medicare program. Exploring federal health care policy. PMID- 1436156 TI - Wilburt Cornell Davison, M.D. one hundredth anniversary: 1892-1992. PMID- 1436157 TI - Why do practitioners contribute to the medical literature? A survey of doctors' writing habits. PMID- 1436158 TI - [Me, tired? Impossible]. PMID- 1436159 TI - [The third emancipation]. PMID- 1436160 TI - [Contact hypersensitivity for corticosteroids]. PMID- 1436161 TI - [The use of imaging techniques for the diagnosis and therapy in icterus with suspected malignant obstruction of the distal bile ducts]. PMID- 1436162 TI - [Value and risks of percutaneous cytological puncture in the preoperative assessment of pancreas tumors]. AB - In a period of a little over two years 34 preoperative fine needle aspiration biopsies were performed in 32 patients with a possible malignant lesion of the pancreas. A cytological diagnosis of cancer was obtained in 22 patients. On follow-up 27 patients, in whom 28 biopsies were performed, proved to have a malignant tumour. The overall sensitivity of fine needle aspiration cytology in diagnosing a malignancy was 77.8%. There were no false positive results (specificity: 100%). Three patients developed serious biopsy-related complications. This relatively low sensitivity and the fact that a biopsy is not without risk leads to the advice not to perform preoperative fine needle aspiration biopsies as a routine in patients in whom curative or palliative surgery is indicated. Percutaneous biopsy is advised and can be useful if no indication for surgery is present because of the patient's condition or the extent of the disease and non-surgical palliation is the treatment of choice. PMID- 1436163 TI - [Percutaneous bile duct drainage; experiences with a new type of endoprosthesis]. AB - Self expandable stents were placed percutaneously in 105 patients with malignant biliary obstruction. Stent diameter was 1 cm; length, 3.5-10.5 cm. Of the 60 patients with common bile duct obstruction, 50 died 0.2-12 months (median 3 months) after stent insertion. Two patients developed recurrent jaundice and cholangitis after 6 and 12 months, respectively. One patient underwent reintervention. Ten patients, one after a successful reintervention, were alive without jaundice 1-8 months (median 5 months) after stent placement. Of the 45 patients with hilar lesions, 26 died 0.7-18 months (median 5 months) after stent placement, five of them with signs of cholangitis. Nineteen are alive 1-21 months (median 7 months) afterwards. Reinterventions were carried out in 13 patients (29%). The most common cause of stent malfunction was tumour overgrowth. Stent related complications were seen in three patients. PMID- 1436164 TI - [Unnecessarily taxing treatment of congenital hip dislocation to be avoided by timely diagnosis at the well-child center]. AB - In 79 children treated in the Sophia Children's Hospital in Rotterdam because of imminent limping due to congenital dislocation of the hip, the contribution of screening tests by physicians of Infant Health Centres to the timely discovery of this disease was examined. When both limitation of abduction of the hip and difference in length of the legs are examined 6 times in the period of 1-8 months of age, the following results in relation to children not or less well screened may be expected: The risk of discovery of the disease at an age when surgery is not excluded, is reduced to one-third. As a result of the shorter delay between discovery and treatment in practice the risk of having to undergo surgery is halved. The risk of discovery at an age when osteotomy according to Salter is required, is nil. In practice the risk of having to undergo osteotomy is reduced to one quarter. Lowering the frequency of the screening tests reduces the contribution. Examination of just limitation of abduction of the hip also appears to reduce the contribution. PMID- 1436165 TI - [Fatal course of acute appendicitis associated with infectious mononucleosis]. AB - The case history is presented of a 10-year-old boy with a fatal combination of acute appendicitis and infectious mononucleosis, in the literature a particularly rare combination. The boy died of a perforative peritonitis. His appendicitis appeared not to be a complication of the infectious mononucleosis. PMID- 1436166 TI - [Neonatal withdrawal symptoms following the use of clomipramine during pregnancy]. AB - The case is described of a neonate who suffered from withdrawal symptoms within 24 hours after birth as a result of the use of clomipramine by the mother during pregnancy. The symptoms consisted of increased irritability, alternating hyper- en hypotonia, hyperreflexia, cyanosis and hypothermia. He was treated with clonazepam with good result. Prescription of clomipramine during pregnancy should be restricted to specific cases and the doses should be kept as low as possible. Because the symptoms are withdrawal symptoms, phenobarbital should not be used as treatment, as it increases drug metabolism by the liver causing an even faster decrease of plasma concentrations of clomipramine. Clonazepam is the drug of choice. PMID- 1436167 TI - [Postmenopausal estrogen replacement therapy and the risk of atherosclerotic cardiovascular diseases]. PMID- 1436168 TI - [The concealed pill with far-reaching consequences]. PMID- 1436169 TI - ['What am I doing here?'; transient amnesia]. PMID- 1436170 TI - [The significance of clinical trials for daily clinical practice]. PMID- 1436171 TI - [Antioxidants and prevention of cardiovascular diseases]. PMID- 1436172 TI - [Cerebral protection following cardiopulmonary arrest: reality, pipe dream or utopia?]. PMID- 1436173 TI - [Quality of life of persons with HIV infection in an academic hospital]. AB - OBJECTIVE: Comparison of the quality of life of asymptomatic (n = 24) and symptomatic (n = 20) HIV-infected patients and description of the changes in quality of life during the symptomatic stage. DESIGN: Prospective study. SETTING: University Hospital Utrecht. METHOD: Every four months questionnaires on quality of life were completed by 44 of 55 consecutive HIV-infected patients. RESULTS: Physically, asymptomatic HIV-infected patients were better off than symptomatic HIV-infected patients; psychologically, however, both groups of patients showed similar responses. During the symptomatic stage the patients' physical functioning diminished further, but feelings of anxiety or depression showed no marked change; self-evaluations of health conditions became slightly more negative with time. PMID- 1436174 TI - [Perinatal registration: a pilot study of matching of data from the National Obstetrics Registration and the National Neonatology Registration]. AB - The application of a statistical matching procedure was tested in a pilot study, linking data from the National Obstetrics Registration (hospital-based) with data from the pilot National Neonatology Registration. Linkage appeared feasible, maintaining anonymity of the registered mother-infant pairs. The perinatal database thus formed was suitable for perinatal epidemiological research. Consequently a continuous perinatal database may be formed from the operational home and hospital based National Obstetrics Registration and the National Neonatology Registration which has started on June 1, 1991, allowing ongoing surveillance of perinatal care in the Netherlands. PMID- 1436175 TI - [Radiofrequency energy as treatment for arrhythmias in patients with accessory atrioventricular pathways]. AB - OBJECTIVE: Evaluation of the use of radiofrequency energy to interrupt accessory atrioventricular pathways. DESIGN: Prospective study. SETTING: University Hospital Maastricht. METHOD: The outcome is presented of radiofrequency catheter ablation of accessory atrioventricular pathways in our first 50 consecutive patients, with a total of 54 accessory pathways. All but one patient suffered from symptomatic tachycardias. A catheter electrode was positioned next to the accessory pathway and 30 second pulses of 40 W radiofrequency energy were used to interrupt the connection. RESULTS: Complete block in conduction was accomplished in 44/54 (81%) of accessory pathways. No complications occurred. Success rate, procedure time and radiation dose were found to be related to the location of the accessory connection. The highest success rate was found in left free wall pathways (24/26; 92%), the lowest in right lateral pathways which seldom occur (1/4; 25%). The total procedure took 1-6 hours. The maximal duration of radiographic imaging was 2.5 hours. CONCLUSION: Although insufficient information on long-term efficacy is available, current results support the use of radiofrequency ablation of accessory pathways in institutions with expertise in the invasive management of cardiac arrhythmias. Technical improvements leading to reduction in procedure time and radiation dose will facilitate acceptance of this technique by patient and operator. PMID- 1436176 TI - [A patient with chronic mucormycosis]. AB - Rhinocerebral mucormycosis was diagnosed in a 75-year-old woman with a history of type II diabetes mellitus. This rare opportunistic infection is caused by fungi belonging to the order of Mucorales. The patient had a severe osteomyelitis of the base of the skull, resulting in complaints of headache and diplopia. She was treated with intravenous colloidal amphotericin B, surgical excision, and later with liposomal amphotericin B. She died of respiratory failure. Mucormycosis is usually a rapidly fulminant infection. This patient showed a remarkably chronic course. PMID- 1436177 TI - [Theo van Gogh's medical record]. PMID- 1436178 TI - [Theo van Gogh's medical record]. PMID- 1436179 TI - [Expectant management in extrauterine pregnancy is possible]. PMID- 1436180 TI - [Does a protein-poor diet delay loss of kidney function?]. PMID- 1436181 TI - [Unrecognized hepatitis following a visit to Pakistan: a case of hepatitis E in The Netherlands]. PMID- 1436182 TI - [Hepatitis E, a new letter in the hepatitis alphabet]. PMID- 1436183 TI - [Risk of an unintentional pregnancy after only one unprotected coitus; observations concerning today's hormonal postcoital contraceptive agents]. PMID- 1436184 TI - [Human aspecific gamma globulin labeled with Indium 111: a new radiopharmaceutic agents for the localization of inflammation and infection foci]. PMID- 1436185 TI - [Oral lichen ruber planus: clinical and immunological aspects]. PMID- 1436186 TI - [Revision of guidelines on endocarditis prophylaxis. Commission on Endocarditis Prophylaxis of the Dutch Heart Foundation]. PMID- 1436187 TI - [Seroprevalence of hepatitis E in The Netherlands]. AB - At serological testing of 269 blood samples from patients sent in for hepatitis diagnostics and of 275 randomly selected samples from blood donors from all over the Netherlands, eight and five samples, respectively, were found to contain a positive antibody titre against hepatitis E virus (HEV). Follow-up samples could be obtained from three patients: in one patient the anti-HEV IgG titre remained unchanged over a period of 6 months, in one other the titre fell below the limit of detection and in the third, the titre increased in a period of 2 weeks. This patient had developed jaundice after a stay in Bangladesh. It is possible that in some patients, hepatitis E is mistaken for hepatitis A. PMID- 1436188 TI - [Experience of sexuality in patients with psoriasis and constitutional eczema]. AB - In order to determine the effect of chronic skin disorders on sexuality a cross sectional study was carried out in the Dermatological Outpatient Clinic of Leiden University Hospital. Fifty-two patients with psoriasis and 25 patients with atopic dermatitis filled in a questionnaire which included items on sexual responsiveness and satisfaction. The response rate was 84%. One-third of the patients, especially those with psoriasis, had problems with dating and starting sexual relationships, and were embarrassed in these relationships. The sexual responsiveness of both male and female patients was below that in the normal population. Women appeared to have more problems in this area then men. Their sexual satisfaction was lower than in the average Dutch population, whereas in men this trend was found to be reversed. Sexual responsiveness did not correlate with the extent of the skin disease or location around genital areas, but was associated with self-esteem and the number of emotional complaints. In the treatment of patients with chronic skin disorders attention should be paid to sexual problems that may arise. Groups that are especially affected are females and young psoriatics who have their first sexual relationship. PMID- 1436189 TI - [Anal dynamic plastic surgery of the gracilis muscle; a new surgical technique for the treatment of fecal incontinence]. AB - OBJECTIVE: To study the clinical outcome of anal dynamic graciloplasty (gracilis muscle transposition and implantation of electric stimulation device) in a consecutive series of 12 patients. DESIGN: Prospective study. SETTING: Maastricht University Hospital. PATIENTS AND METHODS: Twelve patients with incapacitating faecal incontinence were treated using anal dynamic graciloplasty because they were not amenable to other medical management. The data were analysed with emphasis on the clinical outcome, anal manometry, and gracilis muscle composition before and after electric stimulation. Results were considered significant if p < or = 0.05, using the paired Student's t-test. RESULTS: Eight patients achieved complete faecal continence, one patient still has a previously constructed colostomy and in three patients no faecal incontinence could be achieved, due to infections. Median follow-up is now over 18 months (range 16 weeks-5 years). Anal manometry demonstrated an anal pressure increased from 39 mmHg (without stimulation) to 66 mmHg with electric stimulation (mean increase 27 mmHg (CI: 19 35; n = 12, p < 0.01). Gracilis muscle composition showed an increase of type I relatively fatigue-resistant fibres, capable of prolonged contractions, from 45% before stimulation to 64% afterwards (mean increase 19% (CI: 14-21; n = 8, p < 0.01). CONCLUSION: Dynamic graciloplasty is capable of replacing the function of damaged or absent anal sphincters. The construction of a colostomy in patients with incapacitating faecal incontinence can be avoided. PMID- 1436190 TI - [Hepatitis E now also in The Netherlands]. AB - A case report of a male aged 31 who, after a journey to Bangladesh, returned with a disease resembling acute hepatitis A. Closer study revealed a hepatitis E infection. He recovered in slightly over two weeks. PMID- 1436191 TI - [The human Reproductive Programme; current family planning in international scientific perspective]. PMID- 1436192 TI - [Letters from Washington. Health and politics in America; 3 November 1992]. PMID- 1436193 TI - [Hypoglycemia in newborn infants: failing reagent strips]. PMID- 1436194 TI - [Hysteroscopy]. PMID- 1436195 TI - [Distinction between renal and nonrenal hematuria using immunoperoxidase staining of urinary erythrocytes for Tamm-Horsfall proteins]. PMID- 1436196 TI - [Me tired? Impossible]. PMID- 1436197 TI - [Mother knows best; diagnosis of prelingual deafness]. PMID- 1436198 TI - [Unsuccessful exploration of the neck in hyperparathyroidism: how to proceed?]. PMID- 1436199 TI - [Asymptomatic primary hyperparathyroidism: when is surgical treatment indicated?]. PMID- 1436200 TI - [Secondary hyperparathyroidism and the role of surgical treatment]. PMID- 1436201 TI - [Policy in brain metastasis]. PMID- 1436202 TI - [Multi-infarct dementia in nursing home patients; more comorbidity and shorter life expectancy than in Alzheimer's disease]. AB - A retrospective analysis of the medical charts of 117 patients (50 men and 67 women) with multi-infarct dementia took place. All patients admitted to the psychogeriatric nursing home 'Joachim en Anna' in Nijmegen between 1980 and 1989 were studied. The aim of the study was to obtain epidemiological information and to investigate the prevalence of comorbid conditions, prognosis and mortality. The results were compared with patients with Alzheimer's disease. The patients remained in the institute for 1.4 years and the mean total duration of the disease was 5.3 years. About twenty-five percent died in the first three months of admission. Life expectation, counted from time of admission, was 6 years shorter in comparison with Dutch mortality tables. Morbidity frequently seen at admission included circulatory system diseases and cerebrovascular accidents. The risk factor hypertension was seen in a smaller percentage of patients than expected. During the stay the diseases most frequently diagnosed were respiratory and urinary tract infections, adverse effects of drugs, constipation and chronic ulcers of the skin. About twenty percent of the patients were struck by a (recurrent) cerebrovascular accident or a transient ischaemic attack. Most patients died of dehydration or bronchopneumonia. There was, apart from the diagnosis of multi-infarct dementia, no single patient aspect that could predict a poor prognosis. Nursing home patients with multi-infarct dementia are clearly different from patients with Alzheimer's disease. Time spent in the nursing home and duration of disease are shorter. They have more comorbid conditions, especially of a cardiovascular nature, and they have a poor life expectation. PMID- 1436203 TI - [Diathermy excision using a metal loop in the treatment of cervical intra epithelial neoplasms; short-term results in 154 patients]. AB - Intraepithelial neoplasia of the uterine cervix (CIN), proven in colposcopically guided biopsies, can be treated in several ways. With the destruction techniques the lesion is treated by laser evaporation or by cryocoagulation. With the excision methods the transformation zone is excised by cold knife conisation, by laser exconisation or by large loop excision (LLETZ). LLETZ was developed by Cartier in 1977 and can be performed under local anaesthesia on an outpatient basis. In the current investigation 154 women with CIN were treated by LLETZ. In four patients microinvasion was suspected after pathological examination and cold knife conisation was performed, so that 150 patients were available for cytological follow-up after three and six months. After 1989 larger loops and more loops of different sizes were used. Therefore the results in both groups are presented separately. In 22 women CIN residue was found. The treatment in the first period of the study (1985-1988) was effective in 36 of the 55 cases (65%), that in the second period (1989-1991) in 87 of the 95 cases (93%). In the first period the size and endocervical localisation of the lesion significantly affected predict the result of the LLETZ, in the second half of the study these were no longer relevant. Destruction methods lack the possibility of pathological investigation, which is possible with the excision methods. In this way underestimation by the colposcopist of a (micro)invasive carcinoma does not necessarily delay adequate treatment. PMID- 1436204 TI - [Health complaints in relation to quality of swimming water in participants of a triathlon]. AB - Participants in a triathlon in Alphen aan den Rijn, the Netherlands, reported gastrointestinal symptoms to the local health authority. A study was performed to establish the number of complaints and the relation with the microbiological water quality at the surface water swimming site, which met current standards. An epidemiological survey was carried out with a questionnaire among 629 participants, with non-participating relatives as controls. Faecal samples of patients and water samples were investigated by conventional methods. 439 participants and 217 controls completed the questionnaire. 140 participants had at least one gastro-intestinal symptom and 28 (6.4%) had highly credible gastroenteritis. Participants had an odds ratio for gastro-enteritis of 14.7 (95% CI: 2.39-604.45). Electron microscopic examination in six of 12 patients showed viruses able to cause such symptoms. Water samples showed considerable faecal pollution at the time of the triathlon (geometric mean counts: thermotolerant coliforms 725/100 ml; faecal streptococci 23/100 ml). The most likely source is the effluent discharge of the nearby waste water treatment plant. A surface water swimming site meeting current standards does not exclude health complaints among tri-athletes. PMID- 1436205 TI - [Repetitive firing in motor nerve endings: modulation by divalent cations, rhythmic activation and cholinergic agents]. AB - The phenomenon of repetitive firing (RG) in motor nerve endings induced by 4 aminopyridine (4-AP) was studied in cut sartorius frog muscle under the voltage clamp conditions. In the presence of 4-AP (1.10(-4) mol/l) one stimulus applied to the nerve induced two end plate currents (EPC) in half of cells studied (n = 35). The elevation of calcium ion concentration up to 5.4 mmol/l or magnesium to 5-9 mmol/l or rhythmic activity (0.05 Hz and above) abolished RF. Substitution of calcium by strontium or barium enhanced RF (the number of EPC during the burst of RF). EPC with very slow time course were observed in some cells in the presence of barium, that disrupted to the burst of RF by repetitive nerve stimulation. Neostigmine, an anticholinesterase agent, increased the number of EPC in the burst of RF, but alpha-bungarotoxin exerted no effect on the RF. The role of calcium and calcium-activated potassium currents in generation and termination of RF in motor nerve endings is discussed. PMID- 1436206 TI - [Effects of "non-quantal" acetylcholine on the sensitivity of the postsynaptic membrane: action of ouabain and imitation of these effects by exogenous acetylcholine]. AB - Development of postsynaptic potentiation (PSP) and desensitization (DS) caused by "non-quantal" acetylcholine after acetylcholinesterase inhibition was studied by means of ouabain, an agent known to modulate (initially increase and then decrease) the level of non-quantal secretion of ACh. Ouabain had no effect on the MEPC parameters when AChE was active. After AChE inhibition ouabain initially increased the decay time constant of MEPC (tau), i.e. caused postsynaptic potentiation (PSP). This effect of ouabain grew with time between inhibition of AChE and application of ouabain. The PSP stage was followed by shortening of MEPCs decay, due to the development of desensitization (DS), and that process was more pronounced than in control. Applied before AChE inhibition, ouabain had no effect on tau. Thus neither PSP nor DS developed under those conditions. Exogenous ACh (20 nmol/l) applied simultaneously with inhibitor of AChE partially prevented the shortening of MEPCs decay, but decreased the amplitude of MEPC. Applied after MEPCs shortening, exogenous ACh (50 nmol/l) tended to return the initial value of tau. It is concluded that nonquantal ACh produces PSP and DS on the postsynaptic membrane after inhibition of ACh and that the DS persists after cessation of nonquantal secretion for a long time. PMID- 1436207 TI - [Effect of cat motor cortex on the formation of lateral geniculate nucleus responses evoked by contralateral superior colliculus stimulation]. AB - It was shown in experiments on anesthetized cats that motor cortex (MC) stimulated by single current pulse caused formation of the lateral geniculate nucleus (LGN) response. It was established that changes in formation of LGN response evoked by contralateral superior colliculus (SC) stimulation were observed by condition of the precedence of LGN response evoked by stimulation of the MC. The expressiveness level of that decrease depended on intervals between conditioning cortical and testing tectal stimuli. At the same time the stimulation of the MC by single current pulse caused no changes in formation of the visual evoked potential of LGN. However, a significant decrease of the visual response of that part of the SC which stimulation caused formation of the LGN response was observed under the same conditions. The obtained data permit supposing that MC checks realization of the tectal influences on the LGN function on the tectal level. It is assumed that realization of the effect of the saccadic suppression of the LGN function in which accomplishment, as it was supposed earlier, the SC took part, was controlled by the MC phasic influence. PMID- 1436208 TI - [Extra-organ sources of parasympathetic innervation of small intestine in the region of ligament of Treitz]. AB - Localization sites of neurons in the dorsal motor nucleus of cat vagus innervating the duodenal-jejunal region and upper part of the jejunum were investigated using the technique of the retrograde axonal transport of horseradish peroxidase. Most part of the neurons was located within the ventrolateral area of the nucleus from +1.0 to +2.7 mm (according to obex). Morphological features of the ganglion nodosum neurons which organize afferent innervation of the intestine were analyzed. It has been shown that the maximal amount of such neurons is concentrated in the medium and caudal parts of the ganglion. PMID- 1436209 TI - [Dopamine effect on ionic conduction and adenyl cyclase activity in the central nervous system of the pond snail]. AB - The mode of dopamine action (DA) was investigated both on identified neurons (growth hormone producing cells--GHC) and on the membrane fraction of the CNS tissue homogenate. Adenylate cyclase activity (ACA) in the Lymnaea membrane depended on the GTP, stimulated and inhibited by different well known mediators, dopamine action being one of them. DA produced a stimulatory and inhibitory action on ACA. Direction of the DA action depended on the GTP concentration: at lower concentration of the GTP DA was a stimulator of ACA, at higher--an inhibitor. It is shown that inhibitory influence of DA on ACA was prevented by treatment of the membrane of the catalytic subunit of the protein kinase A (cPKA). It is particularly noticeable that inhibitory influence of cPKA-dependent phosphorylation reduced the inhibitory action of ALF4-, a G-protein activator. Effect of DA application on the GHC induced appearance of inward and outward currents through the neuronal membrane. PMID- 1436210 TI - [GTP-dependent dopamine reception in central nervous system tissues in the pond snail]. AB - Guanosine-5'-triphosphate (GTP)-dependent binding of the agonist D1 dopamine (DA) receptor ligand [H3]-SKF 38393 is described. It is shown that binding of [H3]-SKF 38393 with two different populations takes place in the presence of guanylyl nucleotides, when they are absent--with one population. It is demonstrated using GDP-alpha-P33 binding analysis that the GDP in equilibrium with GTP exchange rate gets higher as a result of activation of DA receptors in the membrane from the mollusc nervous tissues. Influence of the catalytic subunit of the protein kinase A (cPKA) on the [H3]-SKF 38393 and GDP-alpha-P33 is investigated. Obvious influence of the cPKA on [H3]-SKF 38393 binding is not observed, while basal and DA-induced GDP in equilibrium with GTP exchange in membranes of the mollusc nervous tissues is considerably inhibited. PMID- 1436211 TI - [Switching effect in the system of equilibrium regulation in man]. AB - Postural reactions evoked in human by bilateral vibration of calf muscles were studied under different conditions: sitting without the feet contact with a support; sitting in an unstable position on the edge of the chair; sitting under conditions of the foot contact with different types of supports (rotating disk, suspended platform, etc.); standing with an asymmetrical load applied to the trunk. It has been shown that local vibration of calf muscles can evoke activation not only of the vibrated muscle or of its antagonist (local effects), but also of extensors and flexors of the knee joint (non-local effects), or of the remote muscular groups, involved in different postural synergies. The concrete pattern of muscle activation is determined by several factors, the most important being the relative position of the body links and interaction of feet with a support. The mental image of the body configuration in the system of internal representation is also very significant. PMID- 1436212 TI - [Responses of medullary and spinal neurons to simultaneous stimulation of two locomotor points]. AB - Responses of neurons in the medulla and cervical segments to simultaneous repetitive (50 pps) stimulation of two locomotor points (LPs) by currents in the range of 1 to 2 thresholds of locomotion were studied. In most cases a neuron responded to stimulation of only one LP. Stimulation of the second LP enhanced usually the firing index of that response, if it was low, diminished it, if it was high and did not influence it, if it was about 0.2. Part of neurons increased the background activity during stimulation of one of LPs though spikes were not locked to stimuli. A sign of influence of the second LP onto that elevation depended on its value. Data about the convergence of inputs from the ipsi- and contralateral midbrain and bulbar LPs on single neurons were obtained too. Possible mechanisms of summation of subthreshold excitation of two LPs during initiation of the locomotion are discussed. PMID- 1436214 TI - [Spatial similarity between crystal cells of various agonists of amino acid receptors and the biological effects of these substances]. AB - Space likeness of crystal cells of GABA, glycine, muscimol and taurine has been estimated by special calculation. The relation between the likeness degree of crystal cells and their biological effect on amino acid receptors is marked. PMID- 1436213 TI - [Effect of monoamines on the responses of frog spinal motor neurons mediated by non-NMDA glutamate receptors]. AB - Adrenaline, dopamine and 5-hydroxytryptamine enhanced fast desensitizing responses of frog spinal motoneurons evoked by L-glutamic acid. Monoamines also enhanced late components of dorsal root EPSP's of motoneurons. These effects of monoamines were prevented by ketamine. Slow in desensitizing responses evoked by L-glutamic acid and EPSP's of motoneurons evoked by stimulation of the reticular formation were not influenced by monoamines. PMID- 1436215 TI - [Recruiting of motor units and changes of their firing rate as mechanisms of muscle contraction control]. AB - Main mechanisms of muscle contraction control: recruiting of motor units and changes of their firing rate are discussed in the review. Relative contribution of these mechanisms at different types of muscular activity (tonic contraction, vibration reflex, locomotion) is considered. PMID- 1436216 TI - [Pain reception in the skin studied with chemical agents]. AB - Cutaneous C-fibre polymodal mechano-heat (CMH) sensory units of narcotized cats have been studied for their responses to the close-arterial injection of potassium, acetylcholine and methacholine to the saphenous artery in subnoxious and noxious concentrations. Subnoxious chemical stimulation has induced low frequency excitation of CMH units. The parameters of CMH units firing during subnoxious and noxious chemical stimulation may be used for estimation of effects of local anesthetics. To achieve local anesthesia it is sufficient to inhibit only high frequency responses in CMH units without a complete block of these sensors. With that end in view the use-dependent blockers of nerve excitation are suggested. The use-dependent inhibition of CMH units was found during mechanical stimulation under the action of lidocaine or n-propylajmaline. The mathematical model of C-fibre has demonstrated the key role of slow changes of membrane ionic permeabilities in determining the firing rate elicited by chemical stimulation. PMID- 1436217 TI - [Focused ultrasound in research on somatic reception]. AB - Focused ultrasound has been used to induce the following skin sensations: tactile and temperature ones; specific and unspecific pain, underskin or deep sensations: tactile sensations and some varieties of pain (muscle, periosteum and so on). It has been established that: somatic reception is attributed to mechanoreception; the same receptive structures are cold and warm ones; ultrasound has the sensibilized action. Sensation differences of corporal and auricular acupuncture points and some accidental skin underskin spots have been investigated. PMID- 1436218 TI - [The pain sensitivity of the skin in chronic psychoemotional stress in man]. AB - The focused ultrasound has been used for the comparative study of skin sensitivity to pain in 51 healthy men and 64 patients with neurasthenia, natural model of the chronic psycho-emotional stress. The patients showed a distinct tendency to a decrease of the pain threshold, lowered adaptation to the repeated threshold stimulus, sensitization. With the presence of the above-mentioned factors the pain syndrome occurred relatively more often. Taking into account the fact that the focused ultrasound of rather high intensity affects, first of all, C-afferents which are not only cutaneous but visceral nociceptors as well, an assumption is made that changes in pain sensitivity in the neurasthenic patients are not limited by skin but develop also in the inner medium forming the pain syndrome. PMID- 1436219 TI - [The modulation of the functional properties of the skin thermoreceptors]. AB - The characteristic property of skin cold receptors is the presence of static and dynamic activity with their maximum at any skin temperature. Parallel with the common properties there are some differences in the temperature range of receptors' functioning, frequency of static and dynamic activity, concentration of sensitive receptors on the skin. Mechanisms of these differences are unknown. It is found that the character of skin cold receptors functioning can be changed in individual life of the organism. Some parameters of static and dynamic activity as well as concentration of cold receptors functioning change both with adaptation of the organism to cold and with a rise of the noradrenaline concentration in blood. The reason of adaptive modifications of skin thermoreceptors may be an increase of their sensitivity to noradrenaline observed with adaptation to cold. It can be supposed that the modulating influence of biological active substances is very important in forming activity and sensitivity of skin thermoreceptors. PMID- 1436220 TI - [The mechanism of the effect of the sympathetic nervous system on skin receptors]. AB - It has been found that smooth muscles play an important role in the mechanism of a sympathetic nervous system effect on the activity of skin receptors. Greater activity of the sympathetic nerve fibres induces higher tension of smooth muscles and thus changes mechanical state of the tissues around the receptors. The latter condition, in its turn, affects the response of receptors to mechanical stimulation. A change in the smooth muscles tension in skin vessels affects the response of receptors to cooling of skin. PMID- 1436221 TI - [The structure of the impulse activity of cold thermoreceptors at different levels]. AB - Impulse activity of cold fibres (n. infraorbitalis) has been studied in acute experiments on anesthetized rabbits, with an uninterrupted fall of the skin temperature from 39 degrees to 7 degrees C with the rate of 0.8 +/- 0.05 degrees/min. Analysis of interspike intervals (ISI) in a discharge of receptors has shown that histograms of ISI changed several times in the studied range of temperatures, which reflects a change of the discharge pattern. Each cold receptor possesses an individual mode of the response, which permits dwelling on perception of different characteristics of the temperature stimulus by a sum of thermoreceptors. PMID- 1436222 TI - [The activity of myelinated nerve fibers to heat and burn exposures of the skin]. AB - Activity of myelinated fibres in the n. saphenus was investigated by the crosscorrelation method in the cat's skin stimulated by heat and burn. The decrease of the total nerve activity under the heat action is proved to be related mostly to a change in A beta-fibres. It is shown that pain caused by heating of the skin over 42 degrees C activated A delta-fibres. The results obtained permit solving the problem of the heat information code from the view point of the flow "pattern" theory. PMID- 1436223 TI - [Changes in the skin receptor responses to their repeated heat stimulation]. AB - It is known that cooling of skin induces contraction of collagen fibres, which leads to deformation and excitation of mechanoreceptors. The action of moderate heat on the skin depresses or terminates its tonic activity. The collagen fibres in this case stretch out and the skin tension slackens. Yet, intense thermal stimulation up to 48 degrees C results in a greater afferent activity. This effect is associated with the so-called thermoreceptors. It is shown earlier that repeated stimulation by intense heat increases skin sensitivity to this stimulus. The paper reports the results of recording the time in which afferent activity increased under repeated stimulation of the skin at temperatures up to 48 degrees C and, simultaneously, of the skin tension variations. For each heating instance the skin stretched and contracted when its temperature approached the normal temperature, i. e. 30 degrees C. However, by the next heating (there was a 3- min. pause between them) the skin tension failed to restore completely. Multiple heating tests have shown a loss of the skin sensitivity, and the time in which increased afferent activity manifested itself has shortened. These two processes are simultaneous, which permits concluding that they are related. PMID- 1436224 TI - [The characteristics of the formation of temperature information in afferent units]. AB - Impulse activity of single afferent fibres of the spinal cord dorsal roots of cats was investigated under local mechanical, heat and cold influence on receptive fields of their skin. These influences did not change the frequency of impulsation, but changed redistribution of interimpulse intervals. It is supposed that formation of polyfunctional properties of single afferent fibres is realized due to their polychannel information. PMID- 1436225 TI - [The regional nature of the temperature sensitivity of human skin]. AB - Thermosensitive points of the man's body skin have been examined in 98 volunteers 20-46 years old living in Alma-Ata in psychophysiological research using temperature and mechanical stimulation. According to thresholds of appearance and quality of sensation two groups of cold-sensitive points and 4 groups of heat sensitive ones were identified. Receptors of each group located in skin in zones of the greatest concentration. Temperature ranges and the number of sensitive points were compared, which revealed different significance of the skin plots in temperature perception. PMID- 1436226 TI - [The generator of locomotor activity as the probable modulator of the afferent flow from the thermoreceptors of the skin fields of the flexor and extensor muscles]. AB - The excitability of flexors and extensors of the upper and low extremities was studied in healthy people and in patients with spasticity during local thermostimulation of their receptive fields using H-reflex (HR). In healthy people the HR was inhibited during cooling and was enhanced during warming. Thermostimulation of the contralateral side caused a contraverse reaction. In patients cooling of skin followed the rise of HR. The obtained data show that the condition of the thermoreceptive fields can influence reflex excitability of motoneurons. The character of this influence depends on the initial condition of the locomotor generator. PMID- 1436227 TI - [The interrelationship of pain and temperature reception in human skin]. AB - Local cooling (14-16 degrees C) and warming (40-42 degrees C) of different crus areas or healthy volunteers have been studied for their effect on pain sensitivity. The latter was estimated by means of the tibialis anterior flexor reflex (FR) and EMC-recording. It was established that changes in FR parameters depended not on the thermostimulus modality, but on its position. The FR was enhanced when the warm or cold stimulus was applied over the ipsilateral tested flexor muscle, and it was mainly inhibited when the thermostimulus was over the extensor or contralateral flexor. An assumption is made that the loss of the temperature modality is caused by convergence of temperature and pain information to the spinal interneurons of the "bimodal type". These neurons change their impulse activity under the effect of both temperature modalities. Different reactions of FR on thermostimulation of different areas of the crus are explained by the locomotor generation control of afferent information. PMID- 1436228 TI - [The role of skin reception in controlling movements]. AB - Skin receptors have been studied in the aspect of diverse phenomenology of their participation in organization of motor activity: from the protective flexor reflex to fine correcting effects from the skin which covers the muscle and the tendon. Analysis of the character of exteroceptive effects on reflector responses, cyclic motions and arbitrary activity has revealed a distinct determination of the effect, its dependence on localization and intensity of the exteroceptive stimulus, a moment of its application (state of motor centres) and so on. It is shown that the proprioceptive correction of the motion which underlies the ring control of the motion is inevitably added by exteroceptive effects incorporated into the same system due to their convergence to the same neuronal mechanisms. Basic moments of neuronal organization and basic mechanisms of sensory (exteroceptive) correction of motor activity are considered. Proceeding from the results of the author's investigations, the role of the premotor zone (the ventral horn, L6,7) interneurons which are not connected initially with afferents in the processes of sensomotor interaction in polysynaptic ways to the motoneuron is determined. It is supposed that these neurons integrate already selected information and form a discrete premise to output systems. PMID- 1436229 TI - Selective monocellular necrosis of Hodgkin's/Reed-Sternberg cells and their immunoreactivity to human serum antinuclear antibodies in NS- and MC-types of malignant lymphogranuloma. AB - The selective (apoptotic) necrosis of Hodgkin's cells in malignant lymphogranuloma appears to be etiologically quite different from focal one due to ischemic-vascular causes. The morphology and supposed etiopathogenesis of this cellular lesion, as well as the karyoclastic process-presumably apoptotic in nature-are briefly described and considered as a mechanism leading to cellular regression with subsequent destructuralization and release of DNA-reactive nucleoprotein material in form of free hematoxylin bodies. An original observation of the immunoreactivity of Hodgkin's cells with antinuclear antibodies of human serum in a case of collagenosis is also described. PMID- 1436230 TI - Studies on the release of interleukin-1 (IL-1), tumor necrosis factor (TNF) and lysozyme from human non-adherent mononuclear cells (nMNC) in vitro after treatment with cisplatin and other biological response modifiers. AB - The supernatants collected from cisplatin, lipopolysaccharide (LPS), muramyl dipeptide (MDP) or recombinant interferon gamma (rIFN-gamma) treated non-adherent mononuclear cells (with NK cell activity) enhanced thymocyte proliferation by a submitogenic concentration of concanavalin A as compared to untreated nMNC. Supernatants collected from cisplatin or rIFN-gamma treated nMNC also demonstrated enhanced cytotoxicity against actinomycin-D treated L929 cells, suggesting that cisplatin or rIFN-gamma treated nMNC release tumor necrosis factor (TNF) into the culture supernatant. On the other hand, supernatant collected from untreated nMNC showed little TNF activity. Treatment of nMNC with cisplatin, LPS, MDP or rIFN-gamma resulted in enhanced release of lysozyme into the culture medium as compared to untreated nMNC. PMID- 1436231 TI - T-lymphocyte subsets (CD4/CD8 ratio) in breast cancer patients. AB - T-lymphocyte subsets (CD4/CD8 antigen positive cells) were determined in peripheral lymphocytes from 48 patients with breast cancer of different stages by flow immunocytometry with the aid of anti-CD4 and CD8 monoclonal antibodies. A broad individual variability of the CD4/CD8 ratio among both healthy donors and breast cancer patients was observed. The average value of CD4/CD8 ratio decreased in groups as follows: Healthy donors and Stage I patients, Stage IIA, IIB and Stage IV breast cancer patients. These differences were generally statistically not significant. The difference between healthy donors and Stage IV breast cancer patients was statistically significant (p < 0.01), if one exceedingly elevated value of the CD4/CD8 ratio was excluded from statistical evaluation. The average CD4/CD8 value in the group of breast cancer patients with lymph node or distant metastases was lower than that of patients without metastases, but their difference was not statistically significant either. PMID- 1436232 TI - Effect of aldehydes on free sulfhydryl groups and glycolysis in extracts of Ehrlich ascites tumor cells and mouse liver. AB - Some saturated and unsaturated aldehydes decreased the content of total sulfhydryl (SH) groups and inhibited the aerobic glycolysis in the extract of Ehrlich ascites tumor cells (EATC). These effects were not observed in normal mouse liver cells. PMID- 1436233 TI - Phosphorus-containing metabolites in anthracycline-resistant murine leukemia P388 cells. AB - The method of 31P nuclear magnetic resonance was used to study in vivo the level of phosphorus-containing metabolites in P388 leukemia cells sensitive or resistant to rubomycin (daunomycin) and its nitroxyl analog-emoxyl. It was shown that decreased content of phosphomonoesters (PME) is characteristic of the resistant strains in comparison with the parent cells. Rubomycin and emoxyl were established not to affect practically the pool of phosphorus-containing metabolites in the cells of the resistant strains, but caused considerable increase of PME level in the cells of the parent strain. PMID- 1436234 TI - Utilization of determining lipid-bound sialic acid for the diagnosis and further prognosis of cancer. AB - In three types of tumors, rectal carcinoma, large intestine carcinoma and bronchogenic carcinoma, the level of lipid-bound sialic acid (LSA) was determined in blood serum before and after surgical operation. In all the cases, there was a significant increase of LSA content in comparison with healthy controls. Considerable increase in LSA values was observed in patients in relapse after surgical intervention. In contrast to this, in patients with regression the LSA levels were lower as compared with LSA levels prior to the surgical intervention. We believe that the method of determining LSA level could be used not only for the diagnosis of cancer, but also for the prognosis. PMID- 1436235 TI - Frequent involvement of Ig heavy chain carrier chromosome 12 in translocations in an Ehrlich-derived mouse tumor cell line. AB - Preferential involvement of chromosome 12, the carrier of Ig heavy chain, in structural rearrangements has been documented in an in vitro derivative of Ehrlich-Lettre mouse ascites tumor. Both copies of chromosome 12 have been found to be involved in Robertsonian and tandem translocations with certain other members of the tumor complement in this near-diploid ascites tumor cell line. PMID- 1436236 TI - The effect of partial hepatectomy on the genotoxicity of aflatoxin B1. II. AB - The influence of partial hepatectomy (PH) on the genotoxic effect of aflatoxin B1 (AFB1) mycotoxin in male Chinese hamsters (Cricetulus griseus) in vivo was studied after a repeated i.p. application of small doses of AFB1 during 8 weeks. The frequency of aberrant cells did not increase after repeated application and persisted throughout the whole period on a relatively stable level. No cumulative genotoxic effect of repeated doses of AFB1 was observed. PH decreased the genotoxic effect of AFB1 only in week 4, while in weeks 6 and 8 no significant differences between hepatectomized and nonhepatectomized animals were recorded. PMID- 1436237 TI - Chromosomes in Hodgkin's disease--analysis of involved lymph nodes. AB - Chromosome studies carried out using lymph nodes of 47 patients with Hodgkin's disease gave analyzable metaphases in 22 patients of which 16 (72.7%) showed chromosome abnormalities. The modal chromosome number ranged from near-diploidy to near-tetraploidy. Chromosomes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 21 and 22 were involved in trisomy and tetrasomy whereas chromosome 17 was involved in monosomy. Structural abnormalities like deletions of chromosomes 1(p13), 6(q24) and addition of chromatin material to chromosomes 11(q13) and 14(q32) were also detected. The involvement of chromosomes 2, 5, 12, 18 and 21 in numerical abnormalities, and chromosome 14(14q+) in structural aberrations was found to be more frequent in Hodgkin's disease. No clinical correlation could be defined between the various chromosome abnormalities and prognosis of these patients. PMID- 1436238 TI - Glutathione S-transferase activity in human breast tumors. AB - The level of total glutathione S-transferase (GST) activity was examined in forty three breast carcinomas (forty tumors from previously untreated patients and three tumors from patients previously treated by chemotherapy), and thirteen benign breast tumors. Cytosolic GST activity was determined according to a spectrophotometric method. Using Student's t-test, significant differences were found between GST levels in these two groups of tumors (p < 0.01). The higher values were found in malignant tumors. The range of values in both malignant and benign tumors was very wide. The relationship between GST activity and hormone receptor status was examined in thirty-three cases for estrogen receptor (ER) status, and thirty-one cases for progesterone receptor (PR) status. The level of hormonal receptors was determined according to the dextran-charcoal technique. No significant difference between the mean levels of GST activity in ER+ and ER tumors was found (p > 0.4), but the difference corresponding to PR+ and PR-tumors approximated the 1% level of significance. The relationship between total GST activity and clinical or pathological parameters was also studied. Significant difference was found between the mean levels of GST activity corresponding to the groups of patients with non-involved nodes, and those having one or more involved nodes, respectively (p < 0.05). No correlation was found with respect to age (p > 0.2), tumor size (p > 0.2), or tumor grade (p > 0.4). Increased levels of GST activity were found in PR-tumors and in tumors with involved axillary nodes. Both groups of tumors are known to have a poorer prognosis. It was concluded that the significance of GST activity as an additional marker of prognosis must be taken into consideration. PMID- 1436239 TI - A multivariant study of pituitary adenoma, obtainment of two logistic regression equations as an auxiliary support in the diagnosis of these tumors. AB - A multivariant analysis was carried out in 120 patients with pituitary adenoma (prolactinoma, HGH-secreting adenoma and nonfunctional adenoma) and an equation was obtained concerning the prolactinoma (whose independent variables were age, galactorrhea, impotence, stage, and pretreatment secretion of ACTH) and another one concerning the nonfunctional adenoma (with age evolution time, visual disturbance evolution and galactorrhea as independent variables). These equations are useful in the differential diagnosis. The internal validity of both equations was obtained by calculating the ROC curve and determining sensibility, specificity and predictive values at the "optimum point" of this curve. PMID- 1436240 TI - Sonography in the diagnosis and therapy monitoring of lymphomas. AB - Multiple ultrasonographic (USG) evaluations of abdomen were performed in 97 patients: 30 with Hodgkin's disease (HD), 60 with non-Hodgkin lymphomas (NHL) and 7 with primary gastric lymphoma (PGL) before or during chemo- or X-ray therapy. In 33% of HD patients USG was normal, while in 63% splenomegaly, in 40% hepatomegaly and in 20% lymph node enlargement were observed. After therapy, in 57% USG was improved and in only 3% of patients worsening was observed. In NHL patients splenomegaly was observed in 70%, hepatomegaly in 60% and lymph node enlargement in 35%. During follow-up, in 49% of patients improvement and in 3% worsening was observed. In 5 patients with PGL no changes were observed, in further 2 patients in Stage IV stomach wall and infiltration of nearest lymph nodes was observed. USG evaluation of abdomen may be useful in staging and therapy monitoring of malignant lymphomas. PMID- 1436241 TI - Cytokine (IFN-alpha, IFN-gamma, IL-1-alpha, TNF-alpha)-induced modulation of HLA cell surface expression in human breast cancer cell lines. AB - Cytokine-induced modulation of HLA expression on the cell surface of four human breast cancer cell lines was determined by continuous flow immunocytofluorometry with the aid of monoclonal antibodies directed to a non-polymorphic determinant of HLA class I and class II (DR) antigen. IFN-gamma and IFN-alpha were potent inducers of HLA class I in all examined cell lines, with decreasing inducibility as follows: BT-20, ZR-75-1, MCF-7 and MDA-MB-468 cells. HLA class II (DR) antigen was highly inducible by IFN-gamma in ZR-75-1 cells, followed by BT-20, MDA-MB-468 and MCF-7 cells. IFN-alpha increased the cell surface expression of DR antigen only in ZR-75-1 cells. IL-1-alpha induced a moderate level of HLA class I antigen in ZR-75-1, BT-20 and MDA-MB-468 cells, and HLA class II (DR) expression only in ZR-75-1 cells. This pattern of cell line inducibility by IL-1-alpha was similar to that induced by TNF-alpha. Differences in inducibility of HLA antigens on human breast cancer cell lines induced by different cytokines may reflect the differences in cytokine inducibility of the original tumor cells. PMID- 1436242 TI - Amine oxidase-mediated cytotoxicity of spermine and epinephrine to human myelogenous leukemia K562 cells. AB - The effects of spermine and beta-adrenoceptor agonists (epinephrine, terbutaline and orciprenaline) in the presence and in the absence of fetal bovine serum (FBS) on human myelogenous leukemia K562 cells viability (V) and survival (N/Nc) were examined. Spermine-FBS significantly decreased both V and N/Nc of K562 cells. Aminoguanidine (AG), an amine oxidase inhibitor, and reduced form of glutathione abolished this effect demonstrating that the spermine-FBS action was amine oxidase-mediated. Epinephrine expressed a strong cytotoxicity to K562 cells which was abolished by pargyline, a specific monoamine oxidase (MAO) inhibitor, as well as by reduced form of glutathione. Terbutaline and orciprenaline exerted no cytotoxic activity to K562 cells cultured in FBS-supplemented medium, independently on the presence of spermine. However, terbutaline at concentrations of over 1 mmol strongly inhibited the cytotoxic effect on spermine-FBS. The relationship between cytotoxicity and chemical structure of beta-adrenoceptor agonists was discussed especially with respect to their stability toward oxidation. PMID- 1436243 TI - Cytochemical study of activated peritoneal macrophages in normal and tumor bearing rats. AB - Enzyme characteristics of in vitro activated peritoneal macrophages of normal and BP6-TU2 tumor-bearing rats were compared with those of nonactivated macrophages. The activating effect of LPS, IFN-gamma, IL-2, TPA, TNF and Zymosan was assessed by the determination of the activities of alpha-naphthyl butyrate esterase (ANBE), tartrate-resistant acid phosphatase (TRAP), beta glucuronidase (BG) and 5'nucleotidase (5'NT). The used individual activators induced the macrophage enzyme activities in different degrees. LPS, TPA and TNF appeared to be the most effective activators of enzyme activities in macrophages of normal rats. IFN gamma, IL-2 and Zymosan were less effective. The macrophages of BP6-TU2 tumor bearing rats were less sensitive to the stimulatory effect of activators with respect to their enzyme activation capacity, except for TRAP activity. The results indicate that enzyme ANBE is an adequate marker of rat peritoneal macrophages. Enzyme TRAP determines the macrophage activation degree more expressively, in comparison with BG and 5'NT. The differences in enzyme activities could be a suitable marker of macrophage activation and might suggest the dependence on the pathway of macrophage stimulation by distinct activators. PMID- 1436244 TI - Estrogen dependence of primary breast cancer--correlation with histologic type and grade. AB - The purpose of this study was to investigate whether histologic type and grade of primary breast cancer are related to the estrogen and progesterone receptors. Our results showed that histologic type influenced the estrogen dependence through histologic grade. There was no difference in the estrogen and progesterone receptor content, when corresponding grades of different histologic types and estrogen dependence were confirmed by quantitative non-parametric analysis. It showed a direct relationship between estrogen and progesterone receptor content in all the three histologic grades and further that histologic grade defines three different groups in regard to progesterone receptor content. PMID- 1436245 TI - The diagnosis of breast cancer--experiences from the community of Kungsbacka, Sweden. AB - In Kungsbacka, Sweden, with about 48,000 inhabitants, the records of all subjects who had been diagnosed to have breast cancer during a 3-year period were studied. The incidence was 41 per 100,000 inhabitants per year. A palpable mass in the breasts was the most common initial sign (77%). Most patients first visited a physician working within the primary health care system. In 94% of the patients a palpable mass in their breasts had been found by the physician. In 16% of the cases a better or a more regular breast self-examination could have reduced the patients' delay. Mean doctor's delay was approximately five weeks. Subjects with no spread to the axillary lymph nodes had a favorable prognosis with a 5-year mortality rate of 12% during the follow-up study period as compared with patients who had distant metastases and/or axillary node involvement, in whom a mortality rate of 67% was observed during the same study period. PMID- 1436246 TI - Survival rates for childhood malignancies in Slovakia. AB - Survival rates (SR) for population-based series of 1564 cases of cancer in children aged 0-14, diagnosed during the decade 1978-1987 in Slovakia and derived from the National Cancer Registry, were examined. The overall 5-year SR (all types of childhood malignancies combined) was 49.8%. Different SR were ascertained for leukemias -43.8%, lymphomas -59.1%, CNS tumors -42.7% and for other remaining diagnostic groups and subgroups of childhood malignancies. Generally, the SR were slightly better for girls than for boys. Cancer patients being diagnosed during the first two years of age showed worse prognosis with a 5 year survival rate of 36.8% as compared to 52.6% for children aged 2-14 at diagnosis. Differences in 5-year survival were also found between urban and rural areas: 56.8% and 48.8%, respectively. The 5-year SR increased during the study period from 48.5% for 1978-1982 to 50.0% for 1983-1987. Comparison of SR from Slovakia with the corresponding rates observed recently in some developed countries indicated possibilities to improve prognosis of childhood malignancies in this country. PMID- 1436247 TI - Influence of tobacco on laryngeal carcinoma in Spain. AB - Spain is one of the countries with the highest incidence of laryngeal cancer in the world. Many risk factors have been linked to this neoplasm, such as tobacco, alcohol and occupation. In order to evaluate the effect of tobacco, a case control study was performed. Cases included 85 patients with cancer of the larynx diagnosed in La Paz, Madrid, between 1983 and 1988, whereas a sample of 170 patients from the same hospital was used as control. Our study revealed that tobacco was significantly associated with laryngeal cancer. Filter-tipped cigarette was shown to be a risk factor as well as consumption of non-filtered cigarettes at first followed by consumption of filter-tipped cigarettes. An association was found between laryngeal cancer and smoking more than 15 cigarettes a day, as well as between cancer of the larynx and being in the habit of smoking for more than 15 years. PMID- 1436248 TI - [Results of the third survey of the structure of neurological inpatient services in former West German districts including West-Berlin]. PMID- 1436249 TI - [Atypical facial pain--quality of IHS (International Headache Society) criteria and psychometric data]. AB - Atypical facial pain is generally an unclearly defined pain syndrome. We tested in 35 patients (31 women, 4 men) with a mean age of 53.2 +/- 14.9 years and a chronic facial pain syndrome the quality of the new diagnostic criteria of the International Headache Society (IHS), at the same time using the SCL-90-R (Self Report Symptom Inventory), to identify any associated psychopathology. In accordance with the literature there is a marked female preponderance, an altogether vague description of symptoms and a long history of incorrect diagnoses. Of note is the high number of invasive procedures (3.5 +/- 3.0). In agreement with the IHS commentary, an operation or injury to the face was a suspected cause in 43%. In contrast to the IHS criteria, we found in our patient sample dysaesthesia (63%), bilateral occurrence (37%), remission periods (57%), pain attacks (23%) and presence of superficial as well as deep pain. Depression is by no means the only psychopathological abnormality in atypical facial pain; a broad spectrum of complaints is seen. The IHS classification appears insufficient to separate atypical facial pain from other primary headache and facial pain syndromes. We therefore suggest a modified version of the IHS criteria for atypical facial pain. PMID- 1436250 TI - [Diagnosis of dysarthria with the "Munich Intelligibility Profile"--construction of the procedure and its use]. AB - No German-based methods for reliable assessment of the intelligibility of dysarthric speech have yet been described. The techniques usually applied in clinical diagnostics take no account of the various factors influencing the understanding of spoken language. They also fail to differentiate between individual patterns of impaired intelligibility. The intelligibility profile presented here controls for the most relevant influencing factors and allows us to discern therapeutically relevant patterns of disturbed intelligibility. The principles of its construction and some applications are presented. PMID- 1436251 TI - [Brain mapping for discriminating age related changes from dementia]. AB - BM-EEG (Brain Mapping) and BM-P300 was studied for age related changes in 63 healthy controls (17.1-87.9 years). Additionally the discriminative power of both functional measures was tested in 21 patients with the clinical diagnosis (NINCDS ADRDA) of probable dementia of Alzheimer type (DAT) of mild to moderate degree (Global Deterioration Scale, 4.2 +/- 2.6). For global and regional absolute and relative power values in the 4 frequency bands alpha, beta, theta and delta, the alpha-peak, P300 latency and amplitudes, quantitative and topographical aspects were analysed. Despite a broad variation of normal values both tests revealed age related changes. For separation between DAT and normal controls BM-EEG was superior to BM-P300. Relative global and regional theta power was the most sensitive parameter to discriminate both groups. BM data are compared with reported findings of traditional EEG and cognitive evoked potentials. PMID- 1436252 TI - [Correlation between neurologic disease and Borrelia burgdorferi antibodies in 800 paired serum/cerebrospinal fluid samples]. AB - Paired serum and cerebrospinal fluid (CSF) samples from 800 patients of a neurological clinic were tested for antibodies to Borrelia burgdorferi. A flagellum enzyme-linked immunosorbent assay was used for antibody screening. All serum/CSF pairs with any elevated antibody response were also tested by a Western blot, a method for confirmation. 65 patients (8.1%) had serum IgG antibodies on ELISA screening and 22 of these (2.8%) were confirmed by Western blot. 20 patients (2.5%) had elevated antibody titers in CSF by ELISA and 12 of these (1.5%) reacted to the Western blot. Clinical features of Bannwarth's syndrome (BS) were present in 12 patients (1.5%) and four patients (0.5%) showed other manifestations of Lyme borreliosis. All patients with Bannwarth's syndrome were positive in serum by both methods and 10 had elevated antibody activity in the CSF proven by the two methods. The combination of a sensitive ELISA for screening and a sensitive and specific Western blot for confirmation reduces the number of positive results but is sensitive in detecting active disease. PMID- 1436253 TI - [Coma polyneuropathy after cardiopulmonary resuscitation]. AB - A 60 year old female patient developed an acute polyneuropathy a few days after a successful cardiopulmonary reanimation followed by coma for several days. Recovery was good as demonstrated at one year follow-up. Residual damage consisted in very mild myoclonic jerks (abortive Lance-Adams syndrome). PMID- 1436254 TI - [Damage to the lateral cutaneous femoral nerve after transfemoral angiography]. AB - We report on two patients with lesions of the lateral cutaneous nerve of the thigh after transfemoral angiography. Symptoms were hypesthesia, dysesthesia and hypalgesia of the right lateral thigh. One patient had no hematoma, the other a hematoma of the medial thigh which did not enlarge thigh circumference. Both patients had had a tight pressure bandage applied for 24 hours. There were no signs of a femoral nerve lesion. Both patients were severely distressed by paresthesia. The numbness subsided after three weeks in one patient, but pain persisted. The other patient had symptoms for over six months. The lateral cutaneous nerve of the thigh is located distinctly lateral to the puncture site in transfemoral angiography. Hence we suggest that the nerve lesion was caused neither by the puncture itself nor by a hemorrhage, but by the tight bandage. PMID- 1436255 TI - [Supranuclear, bilateral and distal-symmetric arm paralysis in central cervical spinal cord trauma]. AB - A case of central spinal cord trauma following hyperextension of the cervical spine and with the finding on MRT of lesions at the level of C 2/3 to C 4/5 disks is reported. A supranuclear paralysis of the lower segments with complete paralysis of the hands and a transient atrophy of the intrinsic hand muscles could be demonstrated. In this connection we refer to the original clinical descriptions of O. Foerster, which have almost been forgotten in the mean time. PMID- 1436256 TI - [Extensive brain injury caused by attempted suicide with an airgun and ultrasound controlled removal of the deep intracranial projectile]. AB - A 65-year-old man attempted suicide by shooting himself in the right temple with an air-gun. There was no loss of consciousness. He remained neurologically asymptomatic. On plain x-rays, the pellet was found in the left frontal lobe and CT-scans revealed a vast cerebral injury with a large hematoma in the right frontotemporal region and along the bullet track. The entry wound was opened and the hematoma was evacuated after removal of small bone fragments and limited osteoclastic enlargement of the bullet hole under the view of the microscope. No attempt was made to remove the pellet through the bullet track in order to avoid additional injury to delicate frontal midline structures. A left frontal burr hole was made and a thin silastic tube, as used for ventricular drainage, was placed with its tip at the projectile under ultrasonic guidance. Along the tube, the pellet was removed through a 5 mm cortical incision with the use of the microscope. The postoperative course was uneventful, the patient had no neurological deficit and early postoperative CT-scans showed complete removal of the hematoma and the bullet without additional brain injury. PMID- 1436257 TI - Effects of ACE inhibition on the course of nephropathy in type I diabetes mellitus. AB - Nephropathy is a severe complication of type I diabetes mellitus. About 25% of all new candidates for renal replacement therapy consist of diabetic patients. Glomerular hyperfiltration is an important causative factor in the development of this nephropathy. Microalbuminuria is the clinical first symptom of glomerular hypertension. New information stresses the importance of angiotensin II. Systemic as well as local reduction of angiotensin II formation can reduce glomerular hyperfiltration. Angiotensin-converting enzyme inhibitors should therefore be considered as first anti-hypertensive agents in type I diabetics with microalbuminuria. PMID- 1436258 TI - Betaxolol in obese hypertensive patients. Long-term effects on blood pressure and serum lipids. AB - The antihypertensive and metabolic effects of betaxolol (20 mg/day) were monitored in 40 patients (17 male), aged 54 +/- 2 yr (mean +/- SEM), with moderate essential hypertension. In a subgroup, consisting of 35 obese patients with a Quetelet index greater than 25.0, blood pressure, heart rate, side effects and biochemical variables were registered bi-monthly for a period of 6 months and after a placebo run-in and run-out period of 2 weeks. Betaxolol decreased blood pressure from 165 +/- 3/107 +/- 1 to 151 +/- 3/95 +/- 2 mmHg after 2 weeks and further to 151 +/- 3/93 +/- 2 mmHg after 6 months (p less than 0.001). Ninety percent of the patients responded to therapy with betaxolol. Heart rate fell from 77 +/- 2 to 64 +/- 1 bpm (p less than 0.001). No significant changes were observed in levels of total cholesterol, LDL-cholesterol or HDL-cholesterol. Triglycerides tended to increase from 2.2 +/- 0.3 to 2.8 +/- 0.4 mmol/l after 4 months of treatment (NS). Renal function was not influenced by betaxolol. Side effects, recorded on a standard questionnaire, did not differ between betaxolol and placebo. In conclusion, betaxolol in a fixed dose of 20 mg/day is an effective antihypertensive drug in the long-term treatment of obese, hypertensive patients, without adverse effects on lipoproteins. PMID- 1436259 TI - Lupus peritonitis presented as vague abdominal complaints in a SLE patient. AB - A 40-yr-old Caucasian woman who had been suffering from systemic lupus erythematosus (SLE) since five years developed vague abdominal complaints whilst under treatment with a low dose of steroids. She had been admitted because of vomiting and abdominal tenderness. The ESR and CRP levels were rising and the C4 level had been persistently low in the preceding months. Normal non-invasive procedures did not allow a diagnosis to be made. Therefore exploratory laparotomy was performed and revealed a non-bacterial peritonitis and an oedematous jejunum. She responded well to a high dose of prednisone. Serositis of the peritoneum as well as bowel vasculitis may be a rare manifestation of SLE despite apparent control of other lupus manifestations. In this patient serositis flares were associated with a rise in CRP level. PMID- 1436260 TI - Familial nonparasitic splenic cysts. AB - Only three times the occurrence of splenic cysts in siblings has been reported. This is the first report of a nonparasitic splenic cyst in mother and daughter. This improbable coincidence may perhaps give a better insight in the histogenesis of splenic cysts. A practical classification of nonparasitic splenic cysts is presented. PMID- 1436261 TI - Octreotide for medullary thyroid carcinoma associated diarrhoea. AB - Medullary thyroid carcinoma associated diarrhoea can be disabling. A 75-yr-old man with metastatic medullary thyroid carcinoma and refractory diarrhoea is described. Subcutaneous administration of the somatostatin analogue, octreotide, 100 micrograms thrice daily, resulted in a sustained improvement in diarrhoea and disappearance of faecal incontinence without reducing calcitonin levels. Octreotide therapy should be considered as symptomatic treatment for otherwise refractory diarrhoea associated with medullary thyroid carcinoma. PMID- 1436262 TI - Recent aspects of pathogenesis and therapy of fulminant elapsing necrosis. PMID- 1436263 TI - Multiple myeloma: prognostic factors and treatment modalities. PMID- 1436264 TI - Successful treatment of a diffuse endocapillary proliferative glomerulonephritis. PMID- 1436265 TI - What is the role of adipsin in obesity? PMID- 1436266 TI - Glucagon-stimulated insulin secretion in patients with type 2 diabetes mellitus: support for the concept of glucose toxicity. AB - Parameters of blood glucose control and insulin secretion were evaluated in 114 patients with type 2 diabetes mellitus, who were no longer controlled satisfactorily by maximal doses of oral hypoglycaemic agents, and compared with those obtained in 11 healthy control subjects, 32 patients with recently diagnosed type 2 diabetes, and 16 tablet-treated and 36 insulin-treated patients. Newly-diagnosed patients were slightly younger (60 +/- 13 yr) and had a slightly higher body mass index (29.4 +/- 6.5 kg/m2). Known duration of diabetes was 9 yr (range 1-37) in secondary failure, and 11 yr (range 1-31) in insulin-treated patients. Fasting blood glucose was the highest (13.8 +/- 2.8 mmol/l) in secondary failure and newly-diagnosed patients (12.6 +/- 3.8 mmol/l) compared to tablet-treated (8.7 +/- 3.3 mmol/l) and insulin-treated patients (9.6 +/- 3.2 mmol/l, p less than 0.05). HbA1c levels were comparably elevated. In insulin treated patients, fasting plasma C-peptide levels were lower relative to the mutually comparable levels in the other 3 diabetic groups. Fasting plasma insulin levels did not differ between the 4 diabetic groups. C-peptide release after glucagon (C-peptide AUC) was comparable in all 4 diabetic groups, although in tablet-treated patients the ratio C-peptide AUC/fasting blood glucose was higher (p less than 0.05). We conclude that the clinical usefulness of determining residual insulin secretion in type 2 diabetic patients is limited, and that the similar reduction of insulin secretion in severely hyperglycaemic newly-diagnosed and secondary failure type 2 diabetic patients supports the concept of "glucose toxicity". PMID- 1436267 TI - Hand bone growth during puberty and in Turner's syndrome. AB - Measurements were made on hand radiographs of normal girls and patients with Turner's syndrome. Normal girls going through puberty display increases in hand bone dimensions which are highly correlated with height and bone age. We report such changes in length and total bone width of metacarpal II (MCII) and proximal phalanx II (PPII), and in combined cortical thickness and cortical area of MCII. For the relative cortical area, the correlations are less pronounced. In comparison with controls of similar height, MCII of patients with Turner's syndrome has greater length and total bone width and combined cortical thickness. Turner patients treated with sex steroids undergo skeletal maturation as well as a rise in MCII relative cortical area (a measure of bone density), but fail to show a commensurate increase in MCII length and in MCII cortical area (a measure of bone mass). It is concluded that in untreated Turner patients, bone density as well as bone mass are normal for the (retarded) bone age, and that sex steroids which promote skeletal maturity likewise raise bone density but not bone mass. The (relative) insensitivity of bone mass and the lack of accelerated statural growth in response to administered sex steroids may be inborn characteristics of the Turner skeleton. PMID- 1436268 TI - Paget's disease with osteolytic lesions: combining medical and surgical treatments. AB - A patient with extensive Paget's disease of bone presented with severe bone pain, hypercalcaemia and a large osteolytic lesion of the femur which developed during long-term therapy with etidronate. Treatment with pamidronate normalized serum calcium concentration and induced a complete biochemical remission. The osteolytic lesion was grafted with bone chips. A recurrence of the Paget's disease was associated with clear autonomous hypercalcaemic hyperparathyroidism. Five years after removal of 3 1/2 hyperplastic parathyroid glands, the patient remains in complete clinical and biochemical remission. These findings illustrate the pitfalls encountered in the management of Paget's disease and the value of combining medical and surgical interventions. PMID- 1436269 TI - Pneumatosis intestinalis in mixed connective tissue disease. AB - Two young female patients with established mixed connective tissue disease (MCTD) are described, in whom the disease course was complicated by intestinal pseudo obstruction and pneumoperitoneum due to pneumatosis intestinalis. Conservative management of this rare complication in MCTD, which included the use of high-flow normobaric oxygen by mask, led to a complete resolution of the abdominal symptoms in both patients. PMID- 1436270 TI - Glyburide-induced cholestatic hepatitis and liver failure. Case-report and review of the literature. AB - As sulphonylurea derivatives are used ubiquitously, the possibility that they may cause liver disease deserves attention. In contrast to the known pattern of reversible parenchymal liver disease due to sulphonylurea derivatives, we describe a fatal case of glyburide-induced cholestatic hepatitis with liver failure. PMID- 1436271 TI - Balkan endemic nephropathy: more questions than answers. PMID- 1436272 TI - Successful ultrasonically guided percutaneous ethanol injection for secondary hyperparathyroidism. AB - Ultrasonically guided percutaneous ethanol injection to all of four enlarged parathyroid glands, which were confirmed by fine-needle aspiration biopsy, was successfully performed in a hemodialysis patient with secondary hyperparathyroidism. In addition to marked reduction of serum parathyroid hormone, the size of parathyroid glands was significantly decreased after the procedure. As an adverse effect, the patient experienced a transient self limiting dysphonia due to right recurrent nerve palsy after the first injection. This procedure may be an effective alternative to surgical treatment or administration of high-dose 1,25(OH)2 vitamin D3 in uremic patients with sonographically verified multiple enlarged parathyroid glands. PMID- 1436273 TI - Fully enzymatic inulin determination in small volume samples without deproteinization. AB - A fully enzymatic method for the determination of inulin in serum or plasma without deproteinization is described. The assay is carried out by means of a fructose determination after hydrolysis of inulin via inulinase and simultaneous oxidation of the native glucose using glucose oxidase and H2O2. This time-saving procedure of high specificity, sensitivity and accuracy requires only small sample volumes. The usefulness of the method is shown by analysis of blood levels in humans and rabbits after an intravenous administration of Inutest. PMID- 1436274 TI - Drug interaction of chloroquine with ciclosporin. PMID- 1436275 TI - Phlebotomy for polycythemia associated with acquired cystic renal disease in a patient on hemodialysis. PMID- 1436276 TI - Treatment with erythropoietin increases intravascular volume contraction during a hemodialysis session. PMID- 1436277 TI - Effect of pyrazinamide on ciclosporin levels. PMID- 1436278 TI - Nonoliguric acute renal failure in non-Hodgkin's lymphoma. PMID- 1436279 TI - Does nephritic factor relate to the disease activity in hypocomplementemic membranoproliferative glomerulonephritis? PMID- 1436280 TI - OKT3-induced sterile peritonitis: report of a case. PMID- 1436281 TI - Acute interstitial nephritis due to endosulfan. PMID- 1436282 TI - Sclerosing encapsulating peritonitis occurring after very-short-term intermittent peritoneal dialysis. PMID- 1436283 TI - Immunohistochemical markers of renal tubular injury and cyclosporin nephrotoxicity in kidney allograft biopsies. PMID- 1436284 TI - Acute uric acid nephropathy following angiography and coronary artery bypass surgery. PMID- 1436285 TI - Amino-aciduria and enzymuria in patients with artificial heart valves. AB - Fifteen patients with artificial heart valves and evidence of chronic intravascular haemolysis were studied for proximal tubular dysfunction. Three patients had haemosiderinuria and haemoglobinuria; 2 had haemoglobinuria alone. Increased urinary amino acid nitrogen occurred in 8, raised fractional beta 2 microglobulin excretion in 2, hypophosphataemia in 4, renal glycosuria in 1 and enhanced fractional urate excretion in 1. Urinary N-acetyl-beta-glucosaminidase (NAG) excretion increased in 7; the mean urinary NAG/creatinine ratio was raised to twice the upper limit of the normal range. Renal haemosiderosis due to chronic intravascular haemolysis could cause tubular injury. PMID- 1436286 TI - Plasma levels of the anaphylatoxins C3a and C4a in patients with IgA nephropathy/Henoch-Schonlein nephritis. AB - Measurements of plasma anaphylatoxins C3a and C4a were carried out as an indicator of in vivo complement activation in 46 patients suffering from IgA nephropathy/Henoch-Schonlein nephritis. There was a significant correlation between plasma levels of C4a and plasma creatinine and urea. We also found a significant correlation of plasma levels of C3a with plasma creatinine. We propose that the measurement of anaphylatoxin levels provides a sensitive indicator of in vivo complement activation and may serve as an additional method for monitoring the progress of disease in these patients. PMID- 1436287 TI - Inhibition of vascular permeability factor production by ciclosporin in minimal change nephrotic syndrome. AB - In order to ascertain whether ciclosporin (Cs) has an inhibitory effect on the vascular permeability factor (VPF) production, various quantities of Cs were added to T lymphocyte cultures from 8 children with minimal change nephrotic syndrome (MCNS) and the VPF activity of culture supernatants was assayed. As a result of the addition of Cs, a dose-dependent inhibition of VPF production was seen. VPF production was inhibited by a level of between 100 and 250 ng/ml of Cs in vitro. The reduction of proteinuria by Cs in MCNS might be due to the inhibition of VPF production. PMID- 1436288 TI - Lipids in the progression of chronic renal failure. AB - Lipid disturbances have been linked to the progression of chronic renal disease. We examined 52 patients with a creatinine clearance (CCr) of 38.5 +/- 7.9 ml/min due to various nephropathies, on free diet. Bimonthly, over a 12-month period, we assessed: serum creatinine (Cr); CCr; daily urinary urea excretion; urinary protein excretion per unit of residual renal function (UProt/CCr); total, HDL, VLDL and LDL cholesterol; triglycerides; Apo A, Apo B. Chronic renal failure was progressive in 22 patients with a slope of 1/Cr-0.00358 +/- 0.00247, stable in 30 with a slope of 0.00420 +/- 0.00285. Lipid parameters did not differ significantly between the two groups but for the lower Apo A and Apo A/Apo B ratio values in the progressive group. Overall slope inversely correlated with basal CCr; in the progressive patients the slope correlated with the percentage variation of UProt/CCr and only partially with the altered Apo profile. PMID- 1436289 TI - Glycosaminoglycans in urolithiasis. AB - To determine if there are differences in urinary glycosaminoglycan (GAG) concentrations, 43 stone-forming patients and 37 healthy control subjects of both sexes were studied. Urinary concentrations of calcium, magnesium, creatinine, uric acid and GAGs were determined. GAGs were measured by the Di Ferrante precipitation procedure followed by the Bitter and Muir reaction. Urinary GAG concentration and daily output were significantly lower in stone-forming patients. The present study clearly demonstrates the decreased urinary GAG concentration and excretion in stone-forming patients and suggests an interaction between GAGs and urate that could modify the inhibitory potency of GAGs. PMID- 1436290 TI - Effect of simvastatin on qualitative and quantitative changes of lipoprotein metabolism in CAPD patients. AB - The efficacy of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, was investigated in 12 patients treated with continuous ambulatory peritoneal dialysis (CAPD), displaying hypercholesterolemia and moderate hypertriglyceridemia. After a 4-week placebo period, simvastatin was administered in increasing doses over a period of 3 months (1st month 10 mg; 2nd month 20 mg and 3rd month 40 mg day-1). Simvastatin reduced total serum cholesterol (300.0 +/- 15.5 vs. 193.0 +/- 8.0; -35%), LDL cholesterol (203.8 +/- 13.0 vs. 104.7 +/- 6.0; -48.0%) as well as apolipoprotein B (132.3 +/- 6.6 vs. 77.8 +/- 2.7 mg/dl; -40%). Furthermore, the ratio of LDL apo B/LDL cholesterol increased significantly (0.55 +/- 0.016 vs. 0.64 +/- 0.027). Another remarkable effect was the reduction of cholesterol concentration in VLDL (47.8 +/- 5.6 vs. 30.4 +/- 5.2; -35%). Therefore, the ratio of triglycerides/cholesterol in VLDL increased (3.57 +/- 0.3 vs. 4.28 +/- 0.29), indicating VLDL formation poor in cholesterol and rich in triglycerides. However, HDL cholesterol increased significantly from 48.6 +/- 4.4 to 57.9 +/- 5.3 mg/dl (23%). Lipoprotein(a) levels were increased as compared to controls (420 +/- 73 vs. 145 +/- 26 U/l), but were not influenced significantly by simvastatin treatment (539 +/- 99 U/l, 3rd month). No evidence for notable clinical side effects and laboratory abnormalities were reported. Measurement of simvastatin plasma levels 12 h after drug administration (single dose 40 mg) showed no detectable plasma values. At present, it appears that CAPD patients with high serum cholesterol are good candidates for the treatment with HMG-CoA reductase inhibitors. PMID- 1436291 TI - A case of POEMS syndrome showing elevated serum interleukin 6 and abnormal expression of interleukin 6 in the kidney. AB - A 46-year-old female presented with POEMS syndrome. Hemodialysis was initiated to control severe anasarca and declining renal function. Corticosteroids were effective in treating renal insufficiency and other symptoms. Serum interleukin 6 (IL-6) was elevated before the corticosteroid therapy but returned to the normal level under the therapy. Immunostaining for the kidney tissue obtained by a renal biopsy showed a diffuse distribution of IL-6 in the glomeruli; thus, in contrast to normal, IL-6 was detected not only in mesangial cells but also in endothelial cells. IL-6 was also distributed in capillaries in the interstitium. While these results suggest a pathogenic role of IL-6 in POEMS syndrome, other factors may be necessary for the full expression of symptoms. Furthermore, it is suggested that chronically stimulated glomerular endothelial cells are capable of producing IL 6. PMID- 1436292 TI - Shape of the relationship between hypertension and the rate of progression of renal failure in autosomal dominant polycystic kidney disease. AB - The effect of hypertension on the rate of progression of renal failure was analyzed in 26 patients with autosomal dominant polycystic kidney disease relating the slopes of progression (linear regression of the reciprocal serum creatinine on time) with the average mean arterial pressure, systolic and diastolic pressure, derived over the entire follow-up period for each patient. Hypertension was found in 19 of the 26 patients. Using simple linear regression, there was no significant correlation between the two variables in any case. Using polynomial regression (quadratic and cubic), this relationship fits a sigmoid (for diastolic pressure) or a negative parabolic curve (for mean arterial pressure and systolic pressure); i.e. the lowest and the highest values of mean arterial pressure and systolic pressure were associated with faster rates of progression. Thus, an appropriate model to study this relationship is not the linear but the polynomial regression. PMID- 1436293 TI - Induction of interleukin 6 synthesis in mouse glomeruli and cultured mesangial cells. AB - Interleukin 6 (IL-6) is an autocrine growth factor of cultured mesangial cells (MC) and intraglomerular IL-6 production is suggested to be closely associated with the pathogenesis of human mesangial proliferative glomerulonephritis (mesPGN). In this study, to elucidate the mechanisms regulating the intraglomerular production of IL-6, we examined what kinds of stimuli are significant in the induction of IL-6 synthesis in vitro and in vivo. Incubation of cultured mesangial cells with interleukin 1 (IL-1) or bacterial lipopolysaccharide (LPS) induced significant IL-6 production, and intravenous injection of IL-1 or LPS into normal BALB/c mice induced significant intraglomerular IL-6 mRNA expression. Furthermore, we indicated in this study that IL-6 mRNA expression was augmented in the glomeruli of mice with immune complex-mediated glomerulonephritis. PMID- 1436294 TI - Cystic radiolucencies of carpal bones, distal radius and ulna as a marker for dialysis-associated amyloid osteoarthropathy. AB - Patients on long-term hemodialysis (HD) are known to develop amyloid osteoarthropathy, evidenced as cystic radiolucencies on X-rays of the affected joints. To study the relationship between cystic radiolucencies and amyloid osteoarthropathy in 394 patients, we classified the severity of the cystic radiolucencies seen in the wrist joint on a 4-point scale and evaluated the association between lesion severity (grade) and several parameters. Biopsy was performed in 8 patients with 11 bone cysts of the wrist joint who had been operated for carpal tunnel syndrome. HD for 10 years or longer, age 50 or older and the presence of carpal tunnel syndrome were associated with severe cyst rating. There was no association between lesion grade and serum level of PTH-C, aluminum or beta 2-microglobulin (B2M). Ten of the 11 biopsied bone cysts in 8 patients with carpal tunnel syndrome demonstrated amyloid deposits which reacted with B2M. We conclude that a cystic radiolucency observed in the wrist joint of a patient undergoing HD indicates the deposition of amyloid. The cyst grade provides a useful marker for the severity of amyloid osteoarthropathy in HD patients. PMID- 1436295 TI - Verapamil increases the nephrotoxic potential of gentamicin in rats. AB - The effect of verapamil on the nephrotoxic potential of gentamicin was examined in rats. Rats were injected with one of the two or both drugs for 6 days and sacrificed 48 h after the last injection. In verapamil-treated rats (5 mg/kg/day), no histological or biochemical evidence of renal injury was detected. In all gentamicin-treated rats (100 mg/kg/day), a significant increase in kidney weight was observed (p less than 0.001). The renal histopathologic lesions were more extensive in rats treated simultaneously with both gentamicin and verapamil. These rats exhibited a decline in body weight earlier (from day 4) than rats injected with gentamicin alone (from day 6). Serum urea nitrogen and creatinine in the latter group of rats were 24.9 +/- 3.7 and 1.1 +/- 0.1 versus 47.4 +/- 8.6 and 1.6 +/- 0.2 mg/dl, respectively, in rats treated with the combined therapy (p less than 0.05). These results indicate that verapamil increases the severity of gentamicin nephrotoxicity. This interaction should be considered as a factor that can potentially increase the nephrotoxic risk associated with gentamicin administration. PMID- 1436296 TI - Effects of acyclovir on renal function. AB - The renal effects of acyclovir (100 mg/kg body weight i.p. for 7 days) were studied in rats. All animals became polyuric and presented an increase in blood urea nitrogen and fractional excretion of sodium and potassium. During hypotonic saline infusion, the acyclovir-treated rats showed higher distal fractional delivery compared to normal rats (27.8 +/- 4.7 vs. 11.3 +/- 0.9%, p less than 0.01) and a lower ratio of free-water clearance to distal sodium delivery (33.5 +/- 7.8 vs. 57.2 +/- 3.9%, p less than 0.02). Following hypertonic saline infusion, the ratio of osmolar to inulin clearance was higher in acyclovir rats (47.8 +/- 7.4%) than in normal rats (27.0 +/- 4.8%), whereas the ratio of free water reabsorption to osmolar clearance was lower in the acyclovir rats (13.6 +/- 4.6 vs. 38.2 +/- 3.2%, p less than 0.01). These findings suggest an effect of acyclovir on the proximal tubule, thick ascending limb and/or inner medullary collecting duct (IMCD). In vitro measurements of 3H2O permeability of perfused IMCD of normal rats showed that vasopressin (50 microU/ml) added to the bath increased the diffusional water permeability (43.4 +/- 4.8 vs. 105.6 +/- 9.1 x 10(-5) cm/s), while in acyclovir rats, the control value (58.8 +/- 9.1 x 10(-5) cm/s) did not increase significantly in the presence of vasopressin (71.3 +/- 13.6 x 10(-5) cm/s). These results suggest that high doses of acyclovir produce azotemia and an abnormal function of the proximal tubule and thick ascending limb associated with resistance to vasopressin of the IMCD. PMID- 1436297 TI - L-arginine reduces glomerular basement membrane collagen N epsilon carboxymethyllysine in the diabetic db/db mouse. AB - The present study was carried out to examine the effect of L-arginine on advanced stage nonenzymatic glycosylation end products in glomerular basement membrane (GBM) as represented by carboxymethyllysine (CML). Twelve db/db mice were given a solution containing a daily dosage of L-arginine of 50 mg/kg body weight orally. Twelve db/db mice served as controls. At the end of the 4-months study period treated animals had significantly lower concentrations of CML (0.084 +/- 0.008, 0.071-0.098 nmol/mumol OH-proline; mean +/- SD, range, p less than 0.01) compared to untreated controls (0.11 +/- 0.018, 0.095-0.152 nmol/mumol OH-proline). In addition, there was a significant positive correlation between GBM thickness and concentrations of CML (r = 0.86, p less than 0.001). We conclude that reduction of CML concentrations in treated db/db mice possibly reflects a beneficial effect of L-arginine on advanced stage nonenzymatic glycosylation end-products in GBM. In addition, measuring CML concentrations might have future clinical implications as a noninvasive parameter for basement membrane thickening. PMID- 1436298 TI - Glomerular epithelial cell endocytosis in puromycin-induced glomerulopathy. AB - Glomerulopathy and nephrotic syndrome were induced in rats by intravenous puromycin aminonucleoside. Ten days after the injection of puromycin, the animals have developed heavy proteinuria. During this phase, glomerular epithelial cell endocytosis was studied by injecting a conjugate of horseradish peroxidase and poly-L-lysine. This conjugate has been shown to be endocytosed by glomerular epithelial cells. The rats were serially sacrificed from 1 min to 24 h after this injection. Peroxidase was localised cytochemically and observed at light and electron microscopy. The early events of endocytosis in glomerulopathy (namely the binding to the plasma membrane, the membrane invagination and the formation of the early vesicles) were qualitatively similar to those in the normal. The later events (the fusion of the vesicles and their movement within the cells) were inhibited. The results show that puromycin aminonucleoside damages epithelial cell endocytotic activity and affects the later processing of the conjugate within the cells. PMID- 1436299 TI - Decreased aortic valve prosthesis-associated haemolysis after changing from haemodialysis to peritoneal dialysis. AB - We report here a chronic haemodialysis patient who had severe anaemia following replacement of his aortic valve. The investigations confirmed a traumatic valve effect. The surgeons were reluctant to replace the valve because of the high cardiothoracic risk and absence of significant leak or stenosis. Furthermore, the patient refused to consider additional surgery. We changed his modality of dialysis to continuous ambulatory peritoneal dialysis; subsequently, there was a dramatic decrease in his transfusion requirement, and the patient was symptomatically and functionally better. A literature search indicates that this therapeutic response has not been reported before. PMID- 1436300 TI - Severe tubulopathy and kidney graft rupture after coadministration of mannitol and ciclosporin. AB - Spontaneous allograft rupture after kidney transplantation is a rare complication usually due to an acute rejection of the interstitial type. In a 32-year-old man kidney transplantation was performed under immunosuppression with prednisolone and ciclosporin (CS). The dose of CS was 5 mg/kg body weight intravenously for the first 24 h, on the 2nd day 10 mg/kg/day orally, with gradually decreasing doses thereafter. The patient remained oliguric in the postoperative period and received additionally 600 ml mannitol solution intravenously for osmodiuresis within a period of 6 days. On the 8th postoperative day, 48 h after the last intravenous infusion of mannitol, spontaneous renal rupture occurred. The CS concentrations in the blood during the days before the rupture were within the upper normal range for effective immunosuppression (300-600 ng/ml). Intraoperatively the kidney appeared enlarged due to edematous swelling of the graft, but it showed no signs of rejection. The histological finding was a toxic tubulopathy with extensive isometric vacuolization and peritubular congestion, a known side effect of both of CS and of mannitol. The rupture was successfully repaired. Thirty-four days after the transplantation diuresis increased and hemodialysis therapy could be discontinued. In a second biopsy of the kidney the signs of toxic tubulopathy with isometric vacuolization were reduced. On the following days the serum creatinine dropped below 160 mumol/l. It can be assumed that the combination of CS therapy and administration of massive and continued doses of mannitol in an oliguric patient with allograft kidney may potentiate severe tubulopathy with concomitant edematous swelling of the graft. This can result in an increasing danger of spontaneous renal rupture. PMID- 1436301 TI - Marked eosinophilia induced by nafamostat mesilate, an anticoagulant in a hemodialysis patient. AB - A 61-year-old Japanese female on hemodialysis developed marked eosinophilia induced by nafamostat mesilate as an anticoagulant for hemodialysis. This is the first case of hypereosinophilic syndrome induced by nafamostat mesilate in a hemodialysis patient. The elevated eosinophil counts (51,900/mm3) are the highest for hemodialysis-associated eosinophilia. This eosinophilia was eliminated after cessation of nafamostat mesilate. We confirmed that the cause of this eosinophilia was nafamostat mesilate by using the challenge test. PMID- 1436302 TI - Treatment of hyperlipidemia in nephrotic syndrome: time for a change? PMID- 1436303 TI - Intraglomerular foam cells and human focal glomerulosclerosis. AB - Experimental evidence suggests a pathogenetic role for lipids in focal glomerulosclerosis (FGS) analogous to atherosclerosis. As foam cells (FC) are an important factor in atherosclerosis, a retrospective comparative study was done to evaluate the significance of intraglomerular FC in human FGS. Glomerular FC infiltration was evaluated in 115 biopsies of FGS, 120 biopsies of membranous glomerulonephritis (MGN) and 50 biopsies of minimal-change disease (MCD). Selected clinical and laboratory data collected at about the time of biopsy were reviewed. The proportion of biopsies showing glomerular FC was much higher in FGS (70%) than in either MGN (12%) or MCD (0%) p less than 0.001. The mean percent (+/- SD) of glomeruli with FC per biopsy was significantly greater in FGS (7.9 +/ 9.9) than in MGN (2.0 +/- 7.8; p less than 0.0001). Of the 14 MGN biopsies with FC, 13 showed superimposed FGS. Mean serum total cholesterol and triglyceride were not significantly higher in FGS than in either MGN or MCD. The results demonstrate a close association of glomerular FC infiltration with FGS. PMID- 1436304 TI - Decreased renal phosphate threshold in patients with gout. AB - Serum and 24-hour urinary phosphate levels in primary gout patients and control subjects were measured. About 45% of gouty patients showed mild hypophosphatemia. However, mean 24-hour urinary excretion of phosphate was significantly elevated as compared with that of controls. Gouty patients showed a significantly decreased tubular reabsorption of phosphate and renal phosphate threshold. It seems that tubular phosphate transport in gouty patients is impaired, and this is the major cause of hypophosphatemia. PMID- 1436305 TI - Evolution of serum prealbumin following hemodialysis: effect of different dialysis membranes. AB - The effects of hemodialysis on the levels of serum prealbumin (pA) were studied on a crossover basis in 17 uncomplicated patients. Bicarbonate dialysate was used exclusively, and two different membranes, cuprophane and polysulfone, were compared. We aimed to prove the induction of an acute-phase response during the procedure. Serum pA, corrected for hemoconcentration, decreased significantly 24 h after the start of cuprophane hemodialysis and returned to the initial value within 48 h. No such change was observed using polysulfone membranes. These results were seemingly correlated with the effects of the membranes on complement activation. It is concluded that cuprophane hemodialysis is indeed associated with an acute-phase response, probably due to interleukin-1 release during the treatment, and that the membrane composition has some role in inducing it. Thus, serum pA analysis may prove useful as an indicator of the biocompatibility of the dialysis procedure. PMID- 1436306 TI - Circulating burst-forming-unit erythroid and the responsiveness to recombinant human erythropoietin in patients on regular hemodialytic treatment. AB - The dose of recombinant human erythropoietin (r-HuEpo) required to correct anemia of end-stage renal disease varies among patients. The possible factors that interfere with the responsiveness to r-HuEpo were not completely known. In 32 patients on regular hemodialytic treatment with marked anemia (Hb 5.6 +/- 0.7 g/dl), we evaluated circulating erythroid progenitor cells [burst-forming-unit erythroid (BFU-E)], erythropoietin, ferritin, folate and 1-84-parathormone levels before r-HuEpo therapy. In 12 patients, the aluminum levels after deferoxamine were also evaluated. The possible correlation between these factors and the response to r-HuEpo therapy was then evaluated. The number of circulating (c) BFU E was highly variable (521 +/- 447 colonies/ml of blood; normal level 742 +/- 192) and does not correlate with erythropoietin, ferritin, folate, 1-84 parathormone or aluminum levels. A direct correlation between basal cBFU-E and the responsiveness to r-HuEpo therapy was recorded while no correlation was found with the other analyzed parameters. We hypothesized that low basal cBFU-E (interleukin-3 deficiency?) could reduce the response to r-HUEpo because of failure of this hematopoietic stem cell compartment to replenish the pool of more mature erythropoietic progenitor cells during the phase of accelerated maturation induced by r-HuEpo. PMID- 1436308 TI - Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease. AB - From a total of 81 patients on maintenance hemodialysis who underwent coronary angiography, 8 patients fulfilled the criteria: significant coronary artery disease, hematocrit less than 27%, reproducible (ECG) positive treadmill test, no disturbance of repolarization in ECG at rest. Exercise stress testing was performed at a hematocrit of 25 +/- 2% and following erythropoietin therapy at a hematocrit of 34 +/- 0.5%. Symptom-limited exercise performance increased in all patients (1.10 +/- 0.3 W/kg b.w. vs. 1.44 +/- 0.31 W/kg b.w., p less than 0.01) as well as exercise duration (489 vs. 362 s, p +/- 0.01). ST segment depression during maximal exercise was reduced from a mean of 2.1 to 0.4 mm (p less than 0.01). It is concluded that amelioration of renal anemia by erythropoietin in dialysis patients with significant coronary artery disease reduces exercise induced myocardial ischemia. PMID- 1436307 TI - Phosphate dialytic removal: enhancement of phosphate cellular clearance by biofiltration (with acetate-free buffer dialysate). AB - Phosphate dialytic removal (PDR) depends in part on the type (acetate or bicarbonate) and the concentration of the buffer dialysate. Plasma phosphate reduction or PDR during a dialysis treatment is the algebraic sum, of phosphate cellular flux (removal or captation) and of phosphate tissular precipitation. High bicarbonate levels induce an intracellular shift of phosphate, thus not available for dialytic removal. On the contrary, acidosis prevents P shifting into the intracellular space, thus more P is available for dialytic removal. In order to evaluate cellular phosphate sequestration (CPS) we tested PDR in a crossover study. Three children were dialyzed (18 sessions) successively using either biofiltration with free buffer dialysate and a constant bicarbonate fluid infusion rate (BF) or using sequential biofiltration (SBF) with an initial controlled acidosis period realized by bicarbonate reinjection fluid rate modelling. PDR was higher in SBF (32 +/- 4 mmol/session) than in BF (24 +/- 6 mmol/session). SBF seemed to be efficient against CPS; it clearly demonstrates that bicarbonate modelling is a promising dialytic approach to enhance PDR. The real clinical relevance of these biological results needs clinical long-term evaluation. PMID- 1436309 TI - Intraglomerular expression of MHC class II and Ki-67 antigens and serum gamma interferon levels in IgA nephropathy. AB - In order to clarify intraglomerular cellular activation and cytokine involvement in IgA nephropathy, the glomerular expression of MHC class II antigens (HLA-DR and DQ) and cellular proliferative nuclear antigen (Ki-67), and serum gamma interferon (gamma-IFN) levels were evaluated in 49 patients with IgA nephropathy. HLA-DR was detected in all but 4 patients in whom glomerular sclerosis was present. HLA-DQ and Ki-67 were observed in 51 and 38% of the patients, respectively. Proteinuria, recent macroscopic hematuria, mesangial proliferation, and extracapillary and endocapillary lesions were more frequent and more severe in HLA-DQ-positive than in HLA-DQ-negative patients. In 10 patients with acute exacerbation, endocapillary lesions and HLA-DQ and Ki-67 expression were present in 70, 80 and 88%, respectively. Serum gamma-IFN levels were high in the patients (2.0 +/- 0.3 U/ml, n = 40), especially during acute exacerbation (3.4 +/- 1.1 U/ml, n = 9). Glomerular HLA-DO and Ki-67 expression correlated with serum gamma IFN levels (r = 0.73, p less than 0.01 for HLA-DQ; r = 0.75, p less than 0.01 for Ki-67). Renal biopsy specimens taken before and after prednisolone and/or urokinase therapy were available from 4 patients. There was strong reactivity to HLA-DQ in the glomerular tufts of all 4 pretreatment samples. However, HLA-DQ reactivity disappeared after treatment in 3 samples, concomitant with normalization of serum gamma-IFN levels. We conclude that serum gamma-IFN levels are related to glomerular HLA-DQ and Ki-67 expression and acute exacerbation in patients with IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436310 TI - A new kindred with hereditary hypophosphatemic rickets with hypercalciuria: implications for correct diagnosis and treatment. AB - Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a new autosomal form of hypophosphatemic rickets, recently described. This disease is characterized, and differs from other forms of hereditary hypophosphatemic rickets and/or osteomalacia by increased serum levels of 1,25-dihydroxyvitamin D, hypercalciuria and complete remission of the disease on phosphate therapy alone. However, only another probable Israeli kindred, and seemingly a few sporadic cases from Europe, North America and Japan have been reported in the literature. We describe here a new kindred of Jewish Yemenite origin (unrelated to other Israeli families) with typical HHRH. Two additional members of this family suffer from a milder asymptomatic form of the disease, which presents as absorptive hypercalciuria without signs or symptoms of bone disease. It seems to us that HHRH is underdiagnosed, due to its similarity to other hypophosphatemic syndromes in clinical, radiological and most biochemical parameters. Therefore, it is recommended that urinary calcium excretion and serum 1,25-dihydroxyvitamin D concentrations be measured in every patient with hypophosphatemic rickets/and or osteomalacia before the initiation of any therapy. The correct diagnosis of HHRN is of immense therapeutic implications. Phosphate therapy alone could cause a complete remission in HHRH, while the addition of active vitamin D metabolites, as is recommended in hypophosphatemic vitamin D resistant rickets, could cause deterioration in the patient's condition. PMID- 1436311 TI - Biosynthesis of methylguanidine in the hepatic microsomal fraction. AB - We have investigated various synthetic mechanisms for the production of methylguanidine, a potent uremic toxin, and reported a role for active oxygen in its biosynthesis from creatinine in studies using isolated hepatocytes. In this study, we turn our attention to the hepatic microsomes. Liver homogenates were made from rats, and various organelles were obtained by centrifugation and incubated with creatinine. The results show that methylguanidine synthesis occurs only in the microsomal fraction in the presence of nicotinamide adenine dinucleotide phosphate, reduced form. The microsomal activity is inhibited by the addition of methimazole, metyrapone, superoxide dismutase, catalase or dimethylsulfoxide. These results suggest that methylguanidine is synthesized from creatinine by microsomes, and at least 2 enzymes are involved, an FAD-containing monooxygenase and a P-450-dependent oxidase based on the inhibitory effect of methimazole and metyrapone, respectively. Moreover, the inhibition by various scavengers of active oxygen suggests that active oxygen plays a role in the intermediate steps of the enzymatic reaction. PMID- 1436312 TI - Quantitative relationships between body weight, kidney weight and nephron size in mongrel dogs. AB - Mammalian species of large stature have larger kidneys with larger nephrons than smaller animals, although this relationship is not linear. In order to investigate whether in animals of different sizes within the same species similar differences exist, a study in mongrel dogs was undertaken. In animals weighing between 9 and 42 kg with kidney weights from 25 to 79 g the area and perimeter of the glomeruli and the cortical width were measured. The number of glomeruli per unit area was counted and corrected for the size of the glomeruli. The results show that larger dogs have larger kidneys and that this enlargement is due to the increase in size of the nephrons and not in their number. PMID- 1436313 TI - Role of glutathione metabolism in the reduction of proteinuria by dimethylthiourea in adriamycin nephrosis. AB - Glutathione (GSH) metabolism, a tissue detoxification pathway, was evaluated in rats with adriamycin nephrosis (AN) treated with dimethylthiourea (DMTU), a free radical scavenger. After 7 days of DMTU, a significant reduction in proteinuria occurred as compared to AN controls (62.4 +/- 13.3 vs. 155.0 +/- 24.0 mg/24 h). A significant increase in renal cortical GSH content as well as glutathione peroxidase (GP) and transferase (GT) activities occurred in DMTU-treated rats as compared to controls. Glutathione monoethyl ester (GME) administration alone reduced proteinuria by 21% in AN, which was not significant despite a large increase in the renal GSH content, however, GP and GT activities were not increased by GME. We conclude that DMTU ameliorates glomerular injury in AN by stimulating GSH metabolism. PMID- 1436314 TI - Correlation between tubulointerstitial nephropathy and glomerular lesions induced by adriamycin. AB - This paper describes a morphometric study of the evolution of tubulointerstitial nephropathy in adriamycin-induced focal and segmental glomerulosclerosis in Wistar rats over 32 weeks old. The earliest changes were located in the glomeruli. In the 10 week of the study, tubulointerstitial nephropathy appeared and, although the interstitial space increased after the 2nd week, this increase only became statistically significant after the 10 week. Proteinuria showed the highest correlation with the interstitial space, however, the interstitial space showed the highest correlation indices with the total number of glomeruli affected and to a lesser extent with adhesions to and thickening of Bowman's capsule. PMID- 1436315 TI - Immune deposits in the glomerular extracellular matrix detected by the quick freezing and deep-etching method. AB - Chronic serum sickness nephritis was induced in rats by sensitization with egg albumin. The glomeruli were then examined by the quick-freezing and deep-etching method with immunohistochemical identification of immune complex deposits on replica membranes. In control rats, the glomerular basement membrane showed a three-layered structure. The middle layer was composed of a compact meshwork of fine fibrils that was connected to adjacent endothelial and epithelial cells by perpendicular fibrils in the inner and outer layers. The mesangial matrix contained a similar but looser meshwork structure. In the nephritic rats, small granular deposits were observed within the meshwork, distorting its fine structure. Larger nodular aggregates extended continuously from the middle layer to the epithelial side. Disruption of the connecting fibrils overlying these larger aggregates was noted. The deposits were stained by antiegg albumin or antirat IgG antibodies. Gold particles immunostaining for the sensitizing antigen were also localized within the deposits. These findings suggest that the deposition of immune complexes occurs in the fibrillary meshworks of the mesangium and lamina densa in this experimental model, with the resultant distortion of their meshwork structures and the formation of nodular aggregates. PMID- 1436316 TI - Role of plasminogen activator inhibitor on nephrotoxic nephritis and its modulation by tumor necrosis factor. AB - To evaluate the suggested imbalance between coagulation and fibrinolysis in the development of glomerulonephritis, plasminogen activator inhibitor (PAI) activity was studied in the plasma of rats with nephrotoxic nephritis. PAI activity rose within 1 h of the injection of nephrotoxic globulin (NTG), peaked at 2 h and returned to the normal range within 24 h. PAI activity was dependent on the dose of NTG and increased significantly during passage through the kidney. PAI activity was also detected in the culture supernatant from isolated glomeruli with nephrotoxic nephritis. Intracapillary fibrin deposits were formed within 2 h; their numbers increased gradually over 24 h. Tumor necrosis factor (TNF) also induced a progressive increase in PAI activity in normal rats. The injection of TNF to rats with NTG synergistically accelerated both the increase in PAI activity and the prevalence of fibrin deposits. These results suggest that PAI may be released from the glomeruli affected by nephrotoxic nephritis and imply that PAI may play a role in the local coagulation in the capillaries of the nephritic kidneys, although this is probably not the only mechanism which explains the continued formation of the glomerular fibrin deposits. PMID- 1436317 TI - Glomerulonephritis associated with Robertsonian translocation t(13;14). AB - We report the first case of glomerulonephritis associated with Robertsonian translocation t(13;14) in a 18-year-old female. The renal biopsy revealed mesangial proliferative glomerulonephritis with mesangial IgG and C3 deposits. The patient also has congenital absence of ovaries and an underdeveloped uterus. Our report suggests that renal abnormalities may be found in patients with Robertsonian translocation. PMID- 1436318 TI - Measurement of vascular access recirculation without contralateral venous puncture. AB - The rate of recirculation is an important variable in calculating the correct dose of dialysis delivered to a patient. Traditionally it is calculated using blood results obtained from the arterial and venous lines and from venous puncture of the opposite arm. To avoid this venipuncture, cessation of the blood pump for 1 or 2 min was attempted to mimic the systemic circulation. This technique underestimated recirculation but was statistically correlated with the result obtained by the classical method, thus it is possible to derive a formula to obtain the recirculation value without contralateral venipuncture. PMID- 1436319 TI - Autosomal dominant polycystic kidney disease complicated by glomerulonephritis. AB - Two patients with autosomal dominant polycystic kidney disease (ADPKD) and concurrent glomerulonephritis are described. Both developed nephrotic-range proteinuria and one showed a concomitant acceleration in the rate of decline of renal function. Subsequent open renal biopsy revealed membrano-proliferative type 1 and mesangio-proliferative glomerulonephritis, respectively. Nephrotic-range proteinuria in the presence of ADPKD, with or without an accompanying decline in renal function, should prompt further investigation to exclude coexisting glomerular disease. PMID- 1436320 TI - Recombinant human erythropoietin for anemia of end-stage renal failure in beta thalassemia trait. PMID- 1436321 TI - A case with membranous glomerulonephritis and myelodysplastic syndrome. PMID- 1436323 TI - Systemic lupus erythematosus and vaccination against hepatitis B. PMID- 1436322 TI - Flow cytometry for crossmatch evaluation in renal transplantation. PMID- 1436324 TI - Persistent wedge-shaped low-density lesions on renal sonography. PMID- 1436325 TI - Scintigraphic evaluation of renal function in heart-beating brain death patients using technetium-99m diethylenetriamine pentaacetic acid. PMID- 1436326 TI - Hypoprothrombinemia and cephalosporins in uremics. PMID- 1436327 TI - Acute renal failure secondary to acute bacterial pyelonephritis. PMID- 1436328 TI - Methemoglobinemia and intravascular hemolysis in a patient with G6PD deficiency. PMID- 1436329 TI - Paramecium colonizing urinary tract of a patient on dialysis: a rare entity. PMID- 1436330 TI - Rhabdomyolysis and acute renal failure as a consequence of heroin inhalation. PMID- 1436331 TI - Glucose-induced insulin secretion in uremia: role of anemia. PMID- 1436332 TI - Do hemodialysed patients contribute to the spread of HCV infection? PMID- 1436333 TI - Predicting glomerular function from adjusted serum creatinine. PMID- 1436334 TI - Dialysis efficacy and itching in renal failure. AB - Itching in nondialyzed uremic subjects and patients on dialysis remains incompletely explained and poorly treated. We evaluated our chronic hemo- and peritoneal dialysis patients for this symptom and synthetically reviewed previous reports on itching and renal failure. We found no biochemical correlates of itching but did find that itching was less with better dialysis as defined by urea kinetic modelling. We conclude that improved dialysis techniques will continue to reduce the prevalence of itching in end-stage renal disease patients. PMID- 1436335 TI - Evaluation of flowcytometric crossmatching in renal allograft recipients. AB - Forty-four cadaver renal allograft recipients who had flowcytometric cross-match (FCXM) testing and sequential quadruple immunosuppression were studied with respect to the number of rejection episodes and the functional viability of the graft in the first year after transplantation. Fourteen of these patients had antibodies to donor T cells by FCXM. All were negative by conventional crossmatch. Multiple-regression analysis with HLA mismatches, panel-reactive antibody (PRA) percentage, flowcytometric channel shifts and transplant number as independent variables revealed that transplant number and high PRA (> 50%) impacted (p < 0.05) on serum creatinine at 1 month and 1 year, and graft survival at 1 year. In first transplants, a positive FCXM had no impact on 1-year graft survival rates; however, in retransplants, a positive FCXM and/or high PRA had a significant negative impact on 1-year graft survival. This study indicates that the FCXM should be utilized for retransplant patients, and in patients with a high PRA, in an attempt to improve graft survival for these high-risk recipients. PMID- 1436336 TI - Hemodialysis intravascular hemolysis and kinked blood lines. AB - Between May 29 and September 13, 1991, 4 patients developed acute intravascular hemolysis during hemodialysis with Monitral-S delivery systems and Hospal BSM A77 blood lines. All had malaise, nausea and headache; 3 had severe abdominal pain and 2 became very ill. Plasma hemoglobins were 3-21 g/l and LDH 542-3,300 IU in the 4 patients. Hepatoglobin became unmeasurable in 3 and was 0.09 g/l in the 4th patient. Soon afterwards, we found the arterial blood line tightly kinked at the dialyzer inlet port in the 4th patient and released it; he developed abdominal pain, hemolysis was present. We then found these lines had an extra long pump segment, and the rest was short and fitted poorly. When put in the first tubing organizer, severe kinking could occur just after the pump segment, causing back pressure but no alarm. We produced early visible hemolysis in a 1-liter circulating closed loop blood system with the blood line kinked either at the dialyzer inlet or just below the first arterial line tubing organizer with 40 g/l free plasma hemoglobin by 30 min. We excluded reported causes of intravascular hemolysis during hemodialysis. No hemolysis occurred before or during the 9 months after we discarded BSM A77 lines. The evidence indicates that kinked blood lines caused the hemolysis. PMID- 1436337 TI - Causes of late renal allograft failure in the ciclosporin era. AB - A single center experience of 514 ciclosporin-treated renal allografts which survived longer than 1 year was reviewed in order to analyze the causes of renal allograft loss beyond the 1st year post-transplantation and the contribution of selected parameters to long-term survival. 83 grafts were lost between 1 and 5 years with the most common causes of graft loss being chronic rejection (54%), death (14%), noncompliance (13%) and sepsis (11%). Actuarial 5-year graft survival rates, decaying from 100% at 1 year, of living related and cadaveric grafts were 88.6 and 79.5%, respectively. Parameters with a substantial influence on long-term survival included the quality of early graft function and incidence of acute rejection in the 1st year post-transplantation. A marker for long-term survival (> 5 years) was a significantly lower serum creatinine (177 mumol/l; < or = 2 mg/dl) at 1 year. We conclude that chronic rejection is responsible for the majority of late graft losses in the ciclosporin era as in the earlier azathioprine period. PMID- 1436338 TI - Neurotoxicity associated with oral acyclovir in patients undergoing dialysis. AB - Neurotoxicity associated with intravenous acyclovir therapy is well documented. We report 4 cases of acyclovir-induced neurotoxicity in dialysis patients receiving oral therapy at a reduced dose. PMID- 1436339 TI - Fibrinolytic capacity in hemodialysis patients treated with recombinant human erythropoietin. AB - A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administered intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of alpha 2-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients. PMID- 1436340 TI - Nodular diabetic glomerulosclerosis without diabetes mellitus. AB - A 66-year-old white man presented with severe chronic renal failure. He had no past or present symptomatic glucose intolerance nor a family history of diabetes mellitus. Several fasting plasma glucose determinations, hemoglobin Alc and an oral glucose tolerance test were normal. Funduscopic ophthalmoscopy and retinal fluorescein angiography did not demonstrate diabetic retinopathy. The kidney biopsy showed nodular diabetic nephropathy, with increased mesangial matrix, thickened glomerular basement membrane, and afferent and efferent glomerular arteriolar hyalinization. The diagnosis of nodular diabetic nephropathy was made in this patient in the absence of past or present or familial evidence of diabetes mellitus. PMID- 1436341 TI - Peritoneal hemosiderosis in pediatric patients with nephrogenic ascites. AB - Nephrogenic ascites associated with maintenance hemodialysis is a complex problem with poorly understood pathophysiology. We report 4 pediatric patients investigated between 1986 and 1990. All the patients treated with maintenance hemodialysis required multiple blood transfusions. Each patient was carefully evaluated for factors potentially relevant to ascites, and serum ferritin levels were found to be extremely high. Peritoneoscopy which was utilized in all patients led to a specific diagnosis of hemosiderosis in the peritoneum and liver biopsies. In 1 patient, lymph node biopsy also showed iron deposition. We believe that iron deposition played a role in changing the permeability of the peritoneum and is presumed to be a pathogenetic factor in nephrogenic ascites. PMID- 1436342 TI - Hypocomplementemia and leukocytosis in diarrhea-associated hemolytic uremic syndrome. AB - Sixty-eight children with diarrhea-associated hemolytic uremic syndrome (D+HUS) were retrospectively examined to assess clinical variables associated with the combination of leukocytosis and hypocomplementemia. There was a statistically significant association between the white blood cell count (WBC) and the level of the third component of the complement system (C3). Children with both a low C3 and a high WBC were significantly younger and required hospitalization for a significantly longer period of time. Although there were also trends to increases in the presence of anuria and central nervous system complications and in the duration of anuria, elevated WBC, thrombocytopenia, dialysis, and hemorrhagic colitis in children with both an elevated WBC and a low C3, these changes did not achieve statistical significance. The presence of a low C3 and an elevated WBC may indicate a subset of children with D+HUS with a more severe episode. PMID- 1436343 TI - Hemodynamic changes in the dog connected to a dialysis circuit: influence of the body temperature. AB - Eighteen sessions in 9 mongrel dogs were carried out to know the hemodynamic effects produced by body temperature variation, when blood passes through a dialysis circuit with a Cuprophan dialyzer, without dialysate contact. The decrease of 2 degrees C in body temperature caused a decrease in heart rate and cardiac index (-8.6 and -17.6%, respectively) without significant changes in blood pressure. The increase of 2 degrees C in body temperature increased the heart rate, the cardiac index and the first derivative of ventricular pressure (+14.8, +17.3 and +27.8%, respectively) with a decrease of 13.6% in the systemic vascular resistance. Blood pressure did not change significantly. We conclude that the dog maintains the hemodynamic stability by two different mechanisms: when body temperature rises, by increasing the cardiac index; when body temperature decreases, by increasing the systemic vascular resistance. PMID- 1436344 TI - Effects of oral adsorbent in the rat model of chronic renal failure. AB - The effects of oral adsorbent, AST-120 (Kureha Chemical Ind. Co., Tokyo), were studied in the rat model of subtotal nephrectomy. In 34 female Sprague-Dawley rats, three quarters of the renal mass were removed from the left kidney by ligation of 3 branches of the left renal artery. One week later, the right kidney was removed. Two days after right nephrectomy, control rats were fed standard rat chow ad libitum, while AST-120-treated rats were fed standard rat chow containing AST-120 ad libitum. The animals were observed for 9 weeks. Of the control rats, some became severely ill and appeared to be almost dying before 9 weeks, while paired AST-120-treated rats appeared well. Body weight was maintained better in AST-120-treated rats than in control rats. At completion of the study, levels of BUN and serum creatinine were lower and glomerular filtration rate and renal plasma flow rate were higher in AST-120-treated than in control rats (p < 0.05), although there was no statistically significant difference in proteinuria. Serum uremic peak 2a measured by high-performance liquid chromatography, which is considered to correspond to uremic toxins, was statistically lower in AST-120 treated rats (p < 0.05). Finally, a marked reduction in the degree of glomerular sclerosis was noted in AST-120-treated versus control rats (p < 0.05). The results indicate that AST-120 is effective in the treatment of chronic renal failure in terms of reducing uremic symptoms as well as preserving renal function and glomerular architecture. The data also indicate that a reduction in uremic toxins could delay the progressive damage of renal function and glomerular architecture in chronic renal failure. PMID- 1436345 TI - Angiotensin-converting enzyme inhibition attenuates hypercholesterolemia and glomerular injury in hyperlipidemic Imai rats. AB - Hyperlipidemic Imai rats spontaneously develop hypercholesterolemia, proteinuria and glomerulosclerosis. We investigated the effect of enalapril, an angiotensin converting enzyme (ACE) inhibitor, on spontaneous hypercholesterolemia and the progressive renal injury in this rat strain. Male Imai rats (n = 7) were treated with enalapril at a dose of 50 mg/l in drinking water starting at 6 weeks of age. Body weight, blood pressure, urinary protein excretion and serum constituents were checked and compared with untreated controls (n = 5) up to 38 weeks of age. Enalapril treatment significantly reduced hypercholesterolemia (247 +/- 41 vs. 102 +/- 13 mg/dl, p < 0.01, at 38 weeks) and proteinuria (766 +/- 290 vs. 206 +/- 119 mg/kg/day, p < 0.01, at 38 weeks). The glomerulosclerosis index (SI) was significantly higher in untreated control rats than in the enalapril-treated group (227 +/- 57 vs. 27 +/- 9, p < 0.01). Although we could not clarify whether hypercholesterolemia is a primary event or secondary to the nephrotic syndrome, these results indicate that the ACE inhibitor has the property to protect remnant glomeruli from glomerulosclerosis in male Imai rats as well as in other animal models in which focal and segmental glomerulosclerosis is believed to represent a common pathologic pattern. This rat strain represents a unique model of a spontaneous proteinuria which can provide an important information on the pathogenesis of human focal and segmental glomerulosclerosis. PMID- 1436346 TI - Relationship between renin, angiotensinogen and histone H2b messenger ribonucleic acid in the maturing rat kidney. AB - Postnatal nephrogenesis and growth of the rat kidney is greatest during the first 10 days of life. The renin-angiotensin system has important growth-promoting effects. To explore the relationship between postnatal renal development and the renin-angiotensin system, we examined the steady-state levels of messenger ribonucleic acid (mRNA) for renin, angiotensinogen, histone H2b (a marker of DNA synthesis) and the structural protein actin. The pattern of expression for renin and histone H2b were similar, with maximal levels of both mRNAs occurring during the first 10 days of life, the time of most marked postnatal nephrogenesis and kidney growth. A different pattern was seen for angiotensinogen mRNA, with low to undetectable levels during the first 15 days of life, and for actin mRNA, with fairly stable expression at the time points examined, providing evidence that the increase in renin and histone H2b mRNA was not due to a nonspecific increase in mRNA in the newborn kidney. In conclusion, the increase in renal histone H2b mRNA during the early postnatal period is consistent with this being a time of increased DNA synthesis. The similar time course for renin mRNA, histone H2b mRNA and previously defined changes in postnatal nephrogenesis suggests a role for the renin-angiotensin system in postnatal nephron formation. PMID- 1436347 TI - Retroviral envelope glycoprotein (gp 70) is not a prerequisite for pathogenesis of primary immunoglobulin A nephropathy in ddY mice. AB - Deposition of a major retroviral envelope glycoprotein, gp 70, in renal glomeruli of ddY mice, an animal model for primary IgA nephropathy, was examined by immunofluorescence. The positive staining of gp 70 was not observed in glomeruli of our substrain of ddY mice at any ages examined using two different anti-gp 70 antisera and three different staining conditions, whereas deposition of IgA, IgG and IgM was manifest in mice aged over 40 weeks. As a control, NZB x NZW F1 mice from 4 months of age onwards showed severe glomerular deposition of gp 70, in keeping with previous reports. Thus, it appears that gp 70 deposition may not be sine qua non for the pathogenesis of IgA nephropathy of all substrains of ddY mice. PMID- 1436348 TI - Renal involvement in leptospirosis: a pathophysiologic study. AB - The kidney involvement in leptospirosis appears to be a special form of acute renal failure due to a higher frequency of polyuric forms and the presence of hypokalemia with an elevated urinary fractional excretion of potassium. Using a clearance technique, we detected higher fractional urinary potassium excretion in leptospirotic guinea pigs (26.5 +/- 4.7%) than in normal animals (14.1 +/- 2.8%, p < 0.05). After blocking distal NaCl reabsorption with furosemide, it was observed that in leptospirotic animals both fractional sodium excretion (40.0 +/- 7.4%) and fractional potassium excretion (136.3 +/- 32.7%) were higher than in normal animals (20.4 +/- 3.8%, p < 0.05, and 43.6 +/- 9.0%, p < 0.05, respectively). Microperfusion studies showed that the normal and leptospirotic medullary thick ascending limb had both identical transepithelial potential difference (+3.7 +/- 0.4 vs. 3.9 +/- 0.2 mV) and relative sodium-to-chloride permeability. The same technique showed that the osmotic water permeability (Posm; 0.9 +/- 0.4 x 10(-5) cm/s.atm) and diffusional permeability (34.7 +/- 6.6 x 10(-5) cm/s) observed in the leptospirotic inner medullary collecting duct (IMCD) in the presence of vasopressin were unchanged, as was also the case for urea permeability (3.74 +/- 0.7 x 10(-5) cm/s). These data show that acute renal failure in leptospirosis is characterized by tubular changes leading to potassium secretion probably due to a decrease in proximal sodium reabsorption. Furthermore, the inability to concentrate urine evidenced by the low P(o)sm present in leptospirotic animals is due, at least in part, to IMCD resistance to vasopressin. PMID- 1436349 TI - Familial hypokalemia-hypomagnesemia or Gitelman's syndrome: a further case. AB - A woman aged 33 years presented hypokalemia and hypomagnesemia associated with renal potassium and magnesium wasting. Her mean 24-hour urinary calcium excretion was strikingly low despite normocalcemia, normal creatinine clearance, normal serum PTH and calcitriol. Normal distal fractional chloride reabsorption [CH2O/(CH2O + CCl)] was noted during water load but was reduced during hypotonic saline infusion. In response to intravenous furosemide (1 mg/kg), the patient showed significant increments in sodium, chloride and magnesium excretion as well as abolition of hypocalciuria. The association of renal calcium transport from magnesium transport together with exaggerated natriuresis after furosemide suggests the presence of a defect in the distal tubule rather than in the loop of Henle. We propose that our patient is affected by the syndrome of primary renotubular hypomagnesemia-hypokalemia with hypocalciuria, known as Gitelman's syndrome. PMID- 1436350 TI - Hyperreninemia and secondary hyperaldosteronism in a patient with pheochromocytoma and von Hippel-Lindau disease. AB - In a 21-year-old Caucasian women with von Hippel-Lindau disease, norepinephrine producing adrenal pheochromocytoma was identified as the underlying cause of severe hypertension. She was found to have extremely elevated levels of circulating renin and aldosterone, and she was markedly hypokalemic. Administration of captopril further enhanced renin secretion, while her blood pressure improved. The patient became normokalemic following tumor removal, and her blood pressure decreased to normal levels with reestablishment of normal circadian blood pressure rhythm. This case demonstrates that, in the absence of renovascular or malignant hypertension, pheochromocytoma can be the underlying cause for the clinical syndrome of hypertension associated with severe hypokalemia and hyperreninemic hyperaldosteronism. PMID- 1436351 TI - Abuse of germanium associated with fatal lactic acidosis. AB - Germanium compounds are marketed as nonprescription drugs in Europe and are recommended by the suppliers for AIDS and metastatic cancer disease. We observed a patient with nonmetastatic breast cancer who died because of severe lactic acidosis (plasma lactate concentration = 27 mmol/l) after ingestion of 25 g of elemental germanium over a 2-months period. Renal failure and hepatotoxicity had newly developed during germanium intake. Postmortem examination revealed severe hydropic vacuolation of tubule cells and the presence of inclusion bodies predominantly in straight proximal tubule cells with normal appearance of renal interstitium and glomeruli. The liver showed panlobular steatosis. Urine, blood and tissue (kidney, liver, muscle, pancreas) levels of germanium were high. Lactic acidosis may have been caused by the combined, germanium-induced renal and hepatic failure (underutilization), but it remains to be seen whether germanium can affect lactate production and/or metabolism directly. PMID- 1436352 TI - Severe hypercalcemia indicating relapse of acute myelocytic leukemia after bone marrow transplantation. PMID- 1436353 TI - Obstructive renal failure due to therapy with sulfadiazine in an AIDS patient. PMID- 1436354 TI - Rhabdomyolysis and acute renal failure following methadone abuse. PMID- 1436355 TI - Galloping caseous pneumonia with miliary dissemination in a renal transplant recipient: emphasis on pretransplant detection and prophylaxis. PMID- 1436356 TI - Human immunodeficiency virus infection and the kidney. PMID- 1436357 TI - Effect of recombinant human erythropoietin on reticulocyte age in hemodialysis patients. PMID- 1436358 TI - Effect of low doses of L-carnitine on the response to recombinant human erythropoietin in hemodialyzed children: about two cases. PMID- 1436359 TI - Treatment of chronic renal failure anemia by recombinant erythropoietin and polycythemia following kidney transplantation. PMID- 1436360 TI - Which antihypertensive treatment in renal vasculitis? PMID- 1436361 TI - Assessment of quality of survival in patients with surgically treated meningioma. AB - A prospective study carried out between 1982 and 1991 encompassed 179 patients who had been operated upon for meningiomas (Neurosurgical University Clinic Heidelberg and Mannheim). History, neurological status, neuroradiological findings, surgical procedure and histology were documented. Within the framework of regular postoperative reexaminations, indices were recorded regarding life quality as standardized by Karnofsky and Spitzer. Following HRDP (Hamburg Rating Scale for Emotional Disturbances), a depression score was evaluated with 32 patients pre and postoperatively. Psychosocial disturbances, which can develop a permanent character, were observed, particularly within the first 12 months after the operation. Depressive moods were noticed quite frequently. The age of the patients proved to be a decisive prognostic factor. PMID- 1436362 TI - [Legal evaluation of intervertebral disk surgery including post-discotomy syndrome]. AB - Although lumbar disc surgery (discectomy) definitely improves the overall situation of the patient in most cases, it does create problems of a hitherto absent kund in about 6% of the patients. Expertising of uncomplicated cases should not be too difficult. However, modulated by individual disposition, a syndrome may develop known as "failed back surgery syndrome" caused by intersegmental loosening, crumbling or fusing and scarification. The pain it causes is decisive for its assessment, not so much any motor or other neurological deficits. In mild cases the loss in capacity for gainful employment may be assessed at between 20% to at the most 30%, but the severely handicapped are unable to cope with their daily life without assistance, their incapacitation amounting to as much as 100%. If the patient concerned is on a job that places stress on this spine, he may be unfit for work even if the affliction is relatively mild. PMID- 1436363 TI - Clinical features of intradural neurinomas in the cauda equina and around the conus medullaris. AB - In this contribution the clinical features of eleven patients suffering from a neurinoma in the cauda equina and around the conus medullaris are analysed. Because of the relative mobility of the roots and the wide space in the spinal canal, tumours arising in the cauda equina or around the conus medullaris can become larger than any other spinal tumours. Lumbago was the predominant symptom as the initial complaint. Nocturnal pain relieved by walking was noticed in one patient. Two cases showed spontaneous remission and relapse. Multiple tumours were found in 6 cases (55%). Macroscopic cyst formation was found in 5 cases (45%). Among the eleven patients, total removal of the tumour, including the involved root, was performed in ten. The numbers of the resected nerve roots were one root in 6 cases, two roots in 2, and three roots in 2. Only one patient showed postoperative slight weakness of the leg. PMID- 1436364 TI - Management of missile wounds of the cerebral dura mater: experience with 69 cases. AB - Over the period of seven months: from July 1991 to January 1992 sixty-nine patients with penetrating head war-injuries, were admitted in our hospital. Missile wounds of the dura mater require in most cases urgent operative management: watertight closure of the dura defects. However, a dilemma still exists as to the best material to be used to restore the missile dural defects. There are several possibilities: an autologous substitute as periosteum (pericranium) from surrounding, fascia of the temporalis muscle, fascia lata, or allograft transplant as lyophilised cerebral dura mater (lyodura). In the group of 69 patients, 7 were treated conservatively, 13 were treated surgically, but without closing the dural wounds because of their critical condition, and in 45 surgically treated patients the dural defects were covered with 53 transplants: with periosteum in 22 patients but 24 coverings, with fascia of temporalis muscle in 2 patients, with lyodura in 6 patients, with fascia lata in 15 patients but 21 coverings. In 4 patients the dura wounds were sutured by interrupted sutures. The best results were obtained in the fascia lata group. PMID- 1436366 TI - [Intracerebral metastasis of a bronchial carcinoid tumor]. AB - The authors report on a female patient of 45 years of age suffering from multiple intracerebral metastases of a bronchial carcinoid. Neurologically, intermittent short-term disturbances of word finding were noticeable. Multiple cerebral foci surrounded by pronounced concomitant oedemas were seen in MR and CT with inhomogeneous contrasts. The diagnosis was confirmed histologically by treatment concepts besides radiotherapy (1, 15, 17) are: intravenous administration of cisplatinum (14), interferon (16) and cyproheptadine (9). The treatment course adopted by the authors is based on an aetiopathogenetic approach, using somatostatin analogues. In the case under report, the somatostatin analogue SMS 201-995 (Sandostatin Sandoz) was applied in doses of 3 x 100 micrograms for a period of eight weeks, in short-term combination with daily doses of methyl prednisolone 40 mg (Urbason Hochst). With this treatment course the patient became free from complaints. No increased growth of the cerebral foci of infection could be observed neuroradiologically during the follow-up period of up to now six months. PMID- 1436365 TI - Unique complications of cerebrospinal fluid shunts in children--a report of two cases. AB - The authors report on two cases with unusual CSF shunt complications. The first case had a peritoneal catheter which migrated down a patent processus vaginalis into a hydrocoele. The second case had an atrial catheter which perforated the atrial wall and came to lie in the pericardium causing an effusion. Clinicians should be aware of the frequent and occasionally bizarre complications of CSF shunting. PMID- 1436367 TI - Cervical intramedullary sarcoidosis. AB - Spinal cord involvement by sarcoid is quite rare. Only fourteen cases of histologically proven sarcoid without meningeal infiltration have been reported. We present the first CT scan description and the second description of the findings on MR imaging of intramedullary sarcoidosis. We also report successful surgical intervention in this case. In a review of surgical reports, we could find only 2 cases of improvement in symptoms after surgical intervention. Additionally, we stress the importance of early diagnosis using the various neuroradiological methods described. We feel that if surgery is performed at an early stage, it may be possible to obtain successful resection of the mass and a good clinical outcome. PMID- 1436368 TI - Recurrence of brain abscess associated with asymptomatic arteriovenous malformation of the lung. AB - On the basis of the data provided by literature the majority of patients with an arteriovenous malformation of the lung who develop a brain abscess suffer from hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease. Only nine cases of brain abscesses in which the arteriovenous malformation of the lung was isolated have been described and in all of these, clinical signs and/or alterations in the laboratory data were detected which can be attributed to the arteriovenous malformation itself. The case taken in this article would seem to be the first case of a recurrent brain abscess in a patient not suffering from Rendu-Osler-Weber with a completely asymptomatic arteriovenous malformation of the lung, both from the clinical point of view and from laboratory data. The authors stress the appropriacy of an angiographic pulmonary study in cases of recurrent brain abscesses, even where the chest X-ray has been negative. PMID- 1436369 TI - A giant hyperostosing meningioma in a child. AB - A case of 15-year-old boy with a giant hyperostotic meningioma is presented. The patient had a huge prominence at the posterior parietal region. The CT scan showed a giant intracranial tumor in the left parieto-occipital region under the hyperostotic bone. The tumor and hyperostotic bone were totally resected with the involved portion of the sagittal sinus. Histological study revealed a meningioma. The presence of such a huge hyperostosis and some peculiarities of childhood meningiomas are discussed. PMID- 1436370 TI - Vasectomy modulates the local effect of intratesticular opioids on the gonad of immature rats. AB - Previous studies indicate that 7 days after testicular administration of naloxone, serum testosterone (T) concentration and basal T secretion in vitro decrease significantly. In neonatal rats, short-term (2 h) intratesticular treatment with 0.3 micrograms (D-Met2-Pro5)-enkephalinamide suppresses steroidogenesis. In the present study, testicular treatment with naloxone or enkephalinamide was combined with hemivasectomy (which also includes transection of the inferior spermatic nerve). When local treatment with naloxone was combined with vasectomy in 15-day-old rats, the opioid antagonist-induced increase in testicular weight, the decrease in basal T secretion of the treated gonad and the drop in serum T level could not be observed 7 days postsurgery, despite the fact that in immature rats, hemivasectomy, by itself, also reduces steroid secretion. Similarly, in 5-day-old animals, the short-term (2 h) effect of testicular enkephalinamide on T secretion was prevented by vasectomy. These data suggest that local testicular actions exerted by endogenous opioid peptides might be modulated by the inferior spermatic nerve. PMID- 1436371 TI - Development of pituitary pro-opiomelanocortin gene and peptide expression: characterization and effect of repeated intermittent maternal isolation. AB - The dynamics of pro-opiomelanocortin (POMC) biosynthesis in the adult rat are altered by demands imposed on the system, such that acute stress increases in the efficiency of anterior pituitary (AP) posttranslational events, while repeated stress increases pretranslational events. In contrast, the developing animal has a limited adrenocortical response to acute stress during the first 2 weeks of life (stress nonresponsive period). In this study, we investigated how the maturing AP and intermediate lobe (IL) POMC cells respond to repeated demand. Measurements of AP and IL POMC mRNA and POMC peptides were performed using Northern gels and radioimmunoassay, respectively. Plasma ACTH and corticosterone measurements were also performed. Maternal isolation, for 1 h on 3 consecutive days, was used as a repeated stress stimulus. The developing AP and IL exhibit an age-related increase in POMC mRNA and peptide levels. On the other hand, AP and IL do not respond to repeated intermittent maternal isolation during the first 2 weeks of life. However, a significant corticosterone release is seen in the 14 and 21-day-old animals. A change in POMC mRNA level is only detected in the 21 day-old AP where levels decrease. Therefore, an adrenocortical response to repeated intermittent maternal isolation predates the appearance of glucocorticoid inhibition of POMC expression in the 21-day-old animal. We propose that an immature neuronal inhibitory circuit during the 3rd week of life causes a sustained corticosteroid response which may in turn trigger AP-delayed feedback. PMID- 1436372 TI - Effect of growth retardation on pituitary luteinizing hormone and hypothalamic neuropeptide Y in ovariectomized sheep. AB - The possible role of neuropeptide Y (NPY) in mediating the relationship between pituitary LH secretion and growth retardation due to restricted feeding was examined in ovariectomized (OVX) prepubertal ewe lambs. One specific objective examined whether there was an inverse relationship between concentrations of NPY in four diencephalic brain regions and pituitary LH secretion in ewe lambs 29-30 weeks old which had been growth retarded since 8 weeks and OVX at 24 weeks. Through dietary restriction, body weight was held constant at 20.7 +/- 0.5 kg in 13 growth-retarded ewes as compared with 48.0 +/- 0.6 kg for 5 age-matched control ewes at 29-30 weeks of age. Episodic LH was quantified at 10-min intervals for 190 min/day on 3 of the 8 days immediately before euthanasia. Serum LH averaged 6.5 +/- 0.6 ng/ml in control ewes with a mean pulse frequency of 1.0 +/- 0.1 pulses/h. Serum LH in growth-retarded ewes was much less episodic (0.2 +/ 0.05 pulses/h) and averaged only 1.2 +/- 0.2 ng/ml. All ewes were euthanized during week 30, and the following brain regions were dissected: basal forebrain, preoptic area, median eminence and remainder of hypothalamus. Following extraction, NPY concentrations (pg/mg of original tissue) were quantified by radioimmunoassay. In each brain region, NPY concentrations were greater (p < 0.05) in 6 growth-retarded ewes than in 5 control ewes (median eminence: 5.2 vs. 0.6; remainder of hypothalamus: 3.3 vs. 0.8; preoptic area: 3.1 vs. 0.8, and basal forebrain: 2.2 vs. 1.2). A secondary objective examined whether the LH and NPY parameters were rapidly altered by transient changes in feed consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436373 TI - Effect of starvation and subsequent refeeding on thyroid function and release of hypothalamic thyrotropin-releasing hormone. AB - Effects of starvation on thyroid function were studied in 5- to 6-week-old (R x U) F1 rats. Starvation lowered plasma TSH in female, but not in male rats. Plasma T4 and T3 levels decreased, whereas the dialysable T4 fraction increased during starvation. Free T4 (FT4) levels decreased rapidly in females, but only after prolonged fasting in male rats. Glucose decreased, and free fatty acid levels increased during starvation. Peripheral TRH levels did not change during food deprivation. Since effects of starvation were most apparent in young female rats, such rats were used to study hypothalamic TRH release during starvation and subsequent refeeding. Basal in vitro hypothalamic TRH secretion was less in starved rats than in control or refed animals. In vitro hypothalamic TRH release in medium with 56 mM KCl increased 3-fold compared to basal release, and in these depolarization conditions TRH release was similar between hypothalami from control, starved and refed rats. In rats starved for 2 days, TRH level in hypophysial portal blood was lower than that of controls. Thus, diminished thyroid function during starvation may at least in part be caused by a reduced hypothalamic TRH release. PMID- 1436374 TI - Melatonin treatment delays reproductive aging of female rat via the opiatergic system. AB - In female rat age-related reproductive decline is accompanied by progressive impairment of the neuroendocrine mechanisms that regulate LH secretion. The biosynthetic activity of the pineal gland is markedly depressed and the nocturnal secretion of melatonin decreases significantly. The aim of the present study was to evaluate whether the nocturnal administration of melatonin via the drinking water (0.4 micrograms/ml) throughout the course of aging from 14 to 24 months of age could (1) influence the age-related changes that occur in basal serum levels of LH and in the LH response to GnRH or to naloxone stimulation at 16, 18 and 20 months of age, and (2) delay the onset of the postreproductive constant estrous anovulatory state as evaluated by the daily recording of vaginal smears and by occurrence of polyfollicular ovaries at 24 months of age. Our results demonstrate that melatonin replacement delays the increase in LH serum levels and the decrease in LH response to GnRH that occur in 18-month-old control animals. Furthermore, they show that melatonin treatment prevents the loss of LH response to naloxone manifested in control rats between 16 and 20 months of age. Melatonin also appears to prevent the progressive increase in the monthly occurrence of estrus phases as well as to decrease the number of rats with polyfollicular ovaries at 24 months of age in comparison to control animals. These results suggest that the age-related decrease in circulating melatonin during the night may contribute to the reproductive decline of aging, and that this effect may involve the central opioid system. PMID- 1436375 TI - Effect of serotonin 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the prolactin response to restraint and ether stress. AB - Serotonin (5-HT) appears to be involved in the central control of the prolactin (PRL) response to suckling and estrogen. Furthermore, 5-HT may participate in the mediation of stress-induced PRL release. In order further to elucidate the role of 5-HT and the type of 5-HT receptor(s) involved in the PRL response to stress, we investigated the effect of blockade of 5-HT1, 5-HT2 or 5-HT3 receptors on the restraint or ether stress-induced release of PRL in male rats. Pretreatment with the 5-HT1 + 2 receptor antagonist methysergide (0.5 or 2.5 mg/kg i.p.) inhibited or prevented the PRL response to restraint or ether stress. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (0.5 or 2.5 mg/kg i.p.) inhibited the response to restraint or ether stress approximately 30 or 60%, respectively. Higher doses of both 5-HT2 receptor antagonists (10 mg/kg i.p.) had a minor inhibitory effect (5-30% for ketanserin and 50% for LY 53857). Prior intraperitoneal administration of the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the restraint stress-induced PRL release dose-dependently. Both compounds inhibited the PRL response to ether stress, but only the effect of GR was dose-related. The maximal inhibitory effect (70% inhibition of the PRL response to restraint or ether stress) was obtained for both compounds at a dose of 0.1 mg/kg. We conclude that serotonergic neurons are involved in the mediation of the stress-induced PRL release by activation of 5-HT1, 5-HT2 as well as 5-HT3 receptors. PMID- 1436376 TI - Activation of central D-1 dopamine receptors stimulates oxytocin release in the lactating rat: evidence for involvement of the hypothalamic paraventricular and supraoptic nuclei. AB - The stimulatory effect of dopamine (DA) on the release of oxytocin (OT) in lactating rats is exerted at the D-1 DA receptor subtype. Because the neural loci mediating this effect have not been identified, the objective of the present studies was to test whether OT release in the lactating rat would be elevated after central administration of a D-1 DA receptor agonist into the third ventricle (3V) or directly into either the rostral paraventricular/anterior commissural nucleus area (PVN/ACN), the central paraventricular nucleus area, or the supraoptic nucleus (SON), all of which contain OT neurosecretory cells. Lactating rats were implanted with a stainless steel cannula directed into one of the above areas or into the arcuate-ventromedial region of the medial basal hypothalamus (MBH), or sites dorsal to the PVN/ACN or SON, which served as anatomical controls. After 6-7 days of recovery, each animal received an intra atrial cannula for sequential blood sampling, and was used in experiments 24 h later. Animals were separated from their litters, and following a period of basal blood sampling, received central microinjections of either vehicle, the D-1 DA receptor agonist SKF-38393, or the D-2 DA receptor agonist quinpirole, and blood samples were removed periodically for 60 min. An injection of angiotensin II (Ang II, 100 ng) was made into each site as a positive control for OT release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436377 TI - Reflexive ovulation in the rat, induced by caesarean section, is blocked by pelvic and/or hypogastric nerve transection. AB - Reflexive ovulation in the rat, induced by caesarean section performed on day 22 of pregnancy, was blocked by prior bilateral transection of the pelvic and/or hypogastric nerves, which convey afferent activity from the reproductive tract. Tubal ova and hemorrhagic ovarian follicles were counted 24 h after bilateral nerve transections or sham neurectomy. Whereas the median numbers of ova and hemorrhagic follicles in the sham neurectomy group were 4.5 and 3.5, respectively, these values in each of the neurectomy groups were 0. The present findings indicate that caesarean section activates the pelvic and hypogastric nerves to trigger ovulation. This suggests that normally the rat is a spontaneous ovulator during the estrous cycle (nonpregnancy) phase of its reproductive cycle, and may become a reflexive ovulator at the parturient phase of its reproductive cycle. PMID- 1436378 TI - Phenoxybenzamine selectively and irreversibly inactivates dopaminergic D2 receptors on primary cultured rat lactotrophs. AB - Lactotrophs have several different kinds of receptors, such as dopaminergic D2, somatostatin, angiotensin II and thyrotropin-releasing hormone receptors, which stimulate or inhibit prolactin release. We have studied the specificity of phenoxybenzamine on receptors in lactotrophs. Phenoxybenzamine is a beta haloalkylamine which alkylates chemically active radicals such as hydroxy, sulfhydryl, and amino groups. This alkylation is an irreversible chemical reaction in contrast to the receptor-secretagogue complex which is present in a state of dynamic equilibrium. Primary cultured rat adenohypophyseal cells were used in this study. A dose-response relationship was examined between concentrations of phenoxybenzamine pretreatment and prolactin release using a monolayer cell culture system. The inhibitory action of dopamine (10 mumol/l) on the control group (13.0 +/- 0.1 ng/ml or 86% inhibition relative to the control) was significantly higher than on the 0.1-mumol/l phenoxybenzamine-pretreated group (39.0 +/- 0.2 ng/ml or 58% inhibition relative to the control), but the stimulatory effect of thyrotropin-releasing hormone on prolactin release was not significantly affected up to a 10-mumol/l phenoxybenzamine pretreatment as compared with the control group. We thus selected a phenoxybenzamine concentration of 0.1 mumol/l for the next series of perifusion experiments in order to examine dynamic changes in prolactin release. The basal prolactin release was decreased to almost half by phenoxybenzamine pretreatment. The inhibitory action of dopamine (0.1 mumol/l containing 0.1 mmol/l ascorbic acid) was significantly less in the phenoxybenzamine-pretreated group (68% of the basal prolactin concentration) than in the control group (31% of the basal concentration).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436379 TI - High concentrations of dopamine and epinephrine protect dopaminergic D2 receptors from inactivation by phenoxybenzamine on primary cultured rat lactotrophs. AB - The effect of a high concentration of catecholamines on phenoxybenzamine pretreatment was examined. The efficacy of the pretreatments was monitored by testing the inhibitory action of dopamine on prolactin release. Phenoxybenzamine is a beta-haloalkylamine which alkylates and irreversibly inactivates adrenergic alpha-receptors in smooth muscle. Dopaminergic D2 receptors share several common characteristics with the alpha-receptors. Primary cultured male rat pituitary cells were used. After phenoxybenzamine (0.1 mumol/l) pretreatment, the inhibitory action of dopamine on prolactin release was significantly reduced in a perifusion system. When the cells were pretreated with phenoxybenzamine in medium containing 0.1 or 1 mmol/l dopamine, the 0.1-mmol/l dopamine did not change the effect of phenoxybenzamine on inactivation of the receptors, but the 1-mmol/l dopamine eliminated the effect of phenoxybenzamine pretreatment. These observations were confirmed with a static monolayer culture system. The observations illustrate that a high concentration of dopamine forms a D2 receptor dopamine complex and protects the D2 from inactivation by phenoxybenzamine. When the cells were pretreated with 0.1 mumol/l phenoxybenzamine in a medium containing 1 mmol/l epinephrine, the effect of the phenoxybenzamine was also eliminated, suggesting that a sufficient amount of D2 receptor-epinephrine complex was formed to protect the receptor from inactivation. The hormone release in response to a secretagogue depends on its affinity and intrinsic activity. It is, therefore, suggested that the intrinsic activity of epinephrine is much lower than that of dopamine on prolactin release, since the D2 receptor-epinephrine complex is as stable as the D2 receptor-dopamine complex, and the inhibitory action of epinephrine on prolactin release is less than 10% of that of dopamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436380 TI - Effect of insulin on LHRH release by perifused hypothalamic fragments. AB - Insulin-deficient states are associated with an impaired function of the hypothalamic-pituitary-gonadal axis, but the mechanisms underlying hypothalamic alterations in experimental diabetes are still unknown. We investigated the effect of glucose concentrations, in the presence and absence of insulin, on LHRH release from perifused hypothalamic fragments from female adult ovariectomized rats. Glucose and insulin were added to the perifusion medium (Earle's, pH 7.4, gassed with 95% O2/5% CO2, flow rate 50 microliters/min). When glucose was absent (in the presence of insulin 10 mU/l), LHRH release was reduced, peak levels being < 5 pg/100 microliters. The addition of glucose (100 and 300 mg/dl), in the absence of insulin, resulted in peak LHRH levels fluctuating around 35 pg/100 microliters (p < 0.05 vs. glucose 0 mg/dl). When glucose (100 or 300 mg/dl) and insulin (10 mU/l) were combined, an eightfold increase in peak LHRH values was observed, and peak levels reached 300 pg/100 microliters (p < 0.05 vs. glucose 100 and 300 mg/dl alone). In conclusion, LHRH release by perifused hypothalamic fragments is dramatically increased by low concentrations of insulin; this occurs only when glucose is available. Acutely elevated glucose levels (from 100 to 300 mg/dl) do not affect LHRH release. PMID- 1436381 TI - Distribution of beta-endorphin immunoreactivity in the arcuate nucleus and median eminence of postpartum anestrus and luteal phase cows. AB - Deficiency in the secretion of luteinizing hormone-releasing hormone (LHRH) from the median eminence (ME) is one of the factors limiting reinitiation of estrous cycles following parturition in cows. In previous studies, administration of naloxone, an opioid receptor antagonist, to postpartum cows increased LH secretion, suggesting that endogenous opioids inhibit the secretion of LHRH. This study employs quantitative light microscopy to describe morphological changes in the distribution of immunoreactive beta-endorphin (ir-beta-END) neurons in the hypothalamus of anestrous early postpartum (EPP, days 10-16, n = 5), midpostpartum (MPP, days 33-43, n = 4) and multiparous cycling cows (CYC, months 12-14, n = 4). Cryostat sections (60 microns) of perfusion-fixed ventral diencephalon and forebrain were immunostained with anti-beta-END serum via the biotin-avidin-peroxidase method or double stained sequentially with anti-LHRH serum, then anti-beta-END serum. In all cows, beta-END immunoreactive perikarya, mostly bipolar neurons, were located in the arcuate and periarcuate nucleus (ARC), with some perikarya in the ME. Within the ARC, the percentage area immunostained for ir-beta-END was greater (p < 0.01) for the CYC than EPP cows, with MPP intermediate but not significantly different from the other groups. Consistent for all cows, the percentage area of ir-beta-END in ventral ARC regions was greater (p < 0.05) than dorsal ARC regions. Fibers from these neurons coursed into the anterior hypothalamus, preoptic area and bed nucleus of stria terminalis. Ventrally projecting fibers entered the ME forming a densely staining band within the external layer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436382 TI - Involvement of excitatory amino acid mechanisms in gamma-hydroxybutyrate model of generalized absence seizures in rats. AB - gamma-Hydroxybutyric acid (GHB), a naturally occurring compound which is synthesized from gamma-aminobutyric acid (GABA), induces bilaterally synchronous spike wave discharges, associated with behavioral changes, reminiscent of petit mal or generalized absence seizures in rats. In the present study, possible involvement of excitatory amino acids (EAAs) in GHB-induced spike wave discharges was investigated. The noncompetitive antagonist of NMDA receptors, MK-801, attenuated GHB-induced spike wave discharges at all doses tested (0.025-1.0 mg/kg) but dose-dependently induced suppression of EEG bursts in GHB-treated animals. The suppression of bursts was never observed with GHB in control experiments. N-Methyl-D-aspartate (NMDA) had a similar effect on GHB-induced spike wave discharges, when it was administered prior to GHB. This effect of NMDA was partially reversed by MK-801. The competitive antagonists of NMDA receptors, (+/-)CPP and CGP 43487 and the antagonist at the strychnine-insensitive glycine site, HA-966, also suppressed GHB-induced spike wave discharges with the EEG progressing to suppression of bursts but were weaker in this regard than MK-801 or NMDA. These data raise the possibility of involvement of excitatory amino acids in the GHB model of absence seizures. PMID- 1436383 TI - Antiparkinsonian drugs memantine and trihexyphenidyl potentiate the anticonvulsant activity of valproate against maximal electroshock-induced seizures. AB - Memantine increased the threshold for electroconvulsions, when administered at 1.0-6.0 mg/kg (i.p.) and given in subthreshold doses of 0.0156, 0.0625, 0.125 and 0.5 mg/kg (i.p.) potentiated the protective efficacy of valproate, against maximal electroshock (50 mA)-induced seizures in mice, lowering the ED50 from 235 to 197, 172, 164 and 130 mg/kg, respectively. Trihexyphenidyl, applied in doses of 30 and 50 mg/kg (i.p.), did not influence the electroconvulsive threshold per se but when combined with valproate, strongly enhanced its anticonvulsant activity against maximal electroshock-induced seizures lowering the ED50 from 206 to 103 and 46 mg/kg, respectively. The chimney test and retention testing in mice revealed that administration of memantine at 0.5 mg/kg (i.p.) or trihexyphenidyl at 30 mg/kg (i.p.) together with valproate in doses of 130 or 103 mg/kg (i.p.), respectively, resulted in motor impairment and caused impairment of long-term memory, similar to the effects of valproate alone, when applied at its ED50 against maximal electroshock. Neither memantine nor trihexyphenidyl altered the total level of valproate in plasma. It may be concluded that the potentiation of the anticonvulsant activity of valproate, by memantine and trihexyphenidyl, is not associated with a pharmacokinetic interaction. PMID- 1436384 TI - Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist. AB - LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats. PMID- 1436385 TI - Phencyclidine-induced desensitization of striatal dopamine release. AB - Increased release of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) from slices of striatum of DBA/2J mouse in response to administration of phencyclidine (PCP) in vitro has been observed to be transient, despite continued exposure to PCP. To determine whether this transient response was a result of depletion of releasable pools, toxicity or an adaptive response (desensitization), the recovery of the response to PCP was evaluated. Slices in the control condition were exposed to PCP (300 microM) during test-exposure only. Slices in the PCP pre exposure condition, were exposed first to PCP (30 microM; pre-exposure) and subsequently to PCP (300 microM; test-exposure). During a washout period (0, 30, 60 or 120 min) between exposures to PCP, the slices were superfused in the absence of PCP. Pre-exposure to PCP diminished the subsequent response to test exposure to PCP (49 and 37% of control for DA and DOPAC, respectively) after 0 min washout. Overflow of DA evoked by PCP returned towards control values but remained decreased (66% of control) after up to 120 min washout. However, overflow of DOPAC did not return to control values after 60 min washout. Thus, the diminished dopaminergic response, resulting from continued exposure to PCP was not due to depletion of the releasable pool or cytotoxicity but rather to a dynamic adaptive response of the dopaminergic neuron to PCP. PMID- 1436386 TI - Phencyclidine and auditory sensory gating in the hippocampus of the rat. AB - The psychotomimetic drug 1-(1-phenylcyclohexyl) piperidine (PCP, phencyclidine) was found to cause a deficit in the gating of the response of the hippocampal neuron to repeated auditory stimuli, which is similar to a particular physiological feature observed in human psychosis. Other drugs, with sigma agonist and/or N-methyl-D-aspartate (NMDA) antagonist effects, were administered and their ability to cause a loss of auditory gating was compared to that of PCP. The rank order of effectiveness was levoxodrol > PCP and (+)-5-methyl-10,11 dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) > N allylnormetazocine (SKF 10047) > dexoxodrol > 3-(+/-)2-carboxypiperazine-4-yl) propyl-1-phosphonate (CPP). Further studies of two of the drugs, PCP and MK-801, showed that selective lesioning of the noradrenergic input with the neurotoxin DSP4, as well as less selective depletion of monoamines with reserpine, blocked the loss of gating. Phencyclidine, and other drugs with the same spectrum of action, most likely disrupt gating by increasing noradrenergic activity through a sigma mechanism. PMID- 1436387 TI - Effects of halothane on membrane potential and discharge activity in pairs of bulbar respiratory neurons of decerebrate cats. AB - In aiming to test the possibility of synaptic interactions, the effect of inhalation of halothane (2% for 90 sec) was studied on 45 out of 88 pairs of respiratory neurons, simultaneously recorded with intracellular and extracellular microelectrodes, in both sides of the ventral respiratory group of decerebrate cats. Halothane produced various effects on these respiratory neurons; namely, depolarization (n = 30) or hyperpolarization (n = 15) of intracellularly recorded neurons, an increase (n = 7) or decrease (n = 38) in the firing of extracellularly recorded neurons. However, with repeated application, the agent produced a consistent effect in a given cell. Spike-triggered averaging of synaptic noise, using spikes of non-antidromically-activated respiratory units, did not reveal any unitary postsynaptic potential but a symmetric synaptic wave of medium-frequency-oscillation (35-50 Hz) in 7 pairs. In addition, power spectral analysis of the membrane potential and spike-interval histogram of the paired neuron, displayed no correlated activity suggestive of synaptic interactions. For all the neuronal pairs examined, halothane produced random effects on their patterns of firing and synaptic waves. The present results suggest that halothane exerts a selective effect on each respiratory neuron and that the lack of a correlated response to application of halothane reflects the lack of synaptic interaction between pairs of bilaterally sampled neurons of the ventral respiratory group. PMID- 1436388 TI - The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant. AB - The pharmacological properties of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5 phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized, centrally acting muscle relaxant, were studied in rats. The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation. The compound, however, showed no effect on the basal discharge of Ia afferent fibers. The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time. In rats anesthetized with halothane, CS-722 did not affect the electroencephalogram (EEG) arousal response, which was elicited by stimulation of the reticular formation. The results of this study suggest that CS 722 can exert a muscle relaxant action, at a dose range at which depression of the ascending reticular activating system was negligible. The results also suggest that depressions of the gamma-motor system and the polysynaptic reflex may contribute to the muscle relaxant action of CS-722. PMID- 1436389 TI - Characterization of the transcallosal response in aged rats and its susceptibility to nootropic drugs. AB - The transcallosal response in aged rats was recorded and its susceptibility to certain nootropic drugs was compared with adult animals, under urethane anesthesia. The transcallosal response in 24-month old rats was significantly reduced in the amplitude of both positive and negative waves, as compared with 5 month old animals. In adult rats, intravenous administration of 100 mg/kg of calcium hopantenate augmented the amplitude of both the positive and the negative waves. Intraperitoneal administration of 300 mg/kg of calcium hopantenate or 10 100 mg/kg of aniracetam increased the amplitude of the negative wave by 20-30% above the control level but had no effect on the positive one. In aged rats, these drugs, given intraperitoneally, also increased the negative wave without affecting the positive one and the degree of augmentation was more prominent; both drugs increased the amplitude of the negative wave by about 190% of the control. These results suggest that the susceptibility to the nootropic drugs became even more striking in older animals, the function in the brain of which are reduced by the natural ageing process. PMID- 1436390 TI - Desensitization of 5-HT1A autoreceptors by chronic administration of 8-OH-DPAT. AB - The function of 5-HT1A autoreceptors was examined by measuring the ability of the 5-HT1A receptor agonist 8-OH-DPAT to reduce 5-HT release in the striatum using in vivo microdialysis. 8-OH-DPAT reduced the release of 5-HT in the striatum. Chronic treatment with 8-OH-DPAT (1.0 mg/kg s.c.) for 7 days, but not 1 day, attenuated the effect of an acute challenge dose of 8-OH-DPAT. The results of the present study indicate that in vivo microdialysis can be used to study the effects of activation of 5-HT1A autoreceptors on 5-HT release and the regulation of 5-HT release by chronic administration of psychoactive drugs. PMID- 1436391 TI - Intracerebral actions of the 5-HT1A agonists, 8-OH-DPAT and buspirone and of the 5-HT1A partial agonist/antagonist, NAN-190, on female sexual behavior. AB - Proestrous rats were infused intracerebrally with 50-1000 ng 8-OH-DPAT, 500 or 2000 ng buspirone or 125-500 ng NAN-190. For each drug, bilateral infusions into the mediobasal hypothalamus inhibited female lordosis behavior and proceptivity and initiated resistive behavior. The effects of the drugs were evident within 5 20 min of infusion and generally lasted for 1-2 hr. The effective sites for 5 HT1A-mediated inhibition of sexual behavior were most concentrated in the ventromedial nucleus of the hypothalamus. Cannulae sites anterior, posterior or dorsal to the ventromedial nucleus or clearly within the IIIrd ventricle were less effective at disrupting lordosis behavior. The inhibition of sexual behavior, following 8-OH-DPAT occurred in a dose-dependent manner and appeared to include the loss of motivation of the female to mate. Buspirone produced similar, but quantitatively smaller, effects on lordosis behavior. NAN-190 slightly, but significantly, suppressed lordosis behavior after either intracerebral or intraperitoneal injection and substantially increased resistive behavior. These results suggest that the inhibition of lordosis behavior, following treatment with 5-HT1A agonists, include an action within the ventromedial nucleus. Moreover, 5-HT1A receptors in this area appear to play a functionally important role in the modulation of the female's "willingness" to mate. PMID- 1436393 TI - The effects of intravenous administration of cholecystokinin on feeding behaviour and release of pituitary hormones in pigs are not mediated by serotonergic (5 HT3) receptors. AB - Two experiments were carried out using the serotonergic (5-HT3) antagonist ondansetron (GR 38032F) to investigate whether the actions of peripherally administered cholecystokinin octapeptide (CCK) in the prepubertal pig might involve 5-HT3 receptors. In Experiment 1, it was shown that ondansetron (10 or 30 mg, i.v.) did not affect the initial feeding response and did not modify the behavioural inhibition induced by a subsequent injection of CCK (1.3 microgram/kg, i.v.). In Experiment 2, it was demonstrated that the nauseogenic action of CCK, indicated by its stimulatory effect on release of vasopressin and cortisol, was not markedly altered by ondansetron (30 mg, i.v.). These results suggest that 5-HT3 receptors play a negligible part in mediating the behavioural and endocrine responses induced by bolus intravenous injections of CCK in this species. PMID- 1436394 TI - 4-Bromo-6-nitroquipazine: a new ligand for studying 5-hydroxytryptamine uptake sites in vivo. AB - The present study was undertaken to evaluate 2 bromo-derivatives (4-bromo-6 nitroquipazine and 6-bromoquipazine) of quipazine as potential ligands for studying 5-hydroxytryptamine (5-HT; serotonin) uptake sites in the brain in vivo. The inhibition experiments of [3H]5-HT uptake into synaptosomes from rat brain and of the binding of [3H]6-nitroquipazine to membranes of rat brain showed that 4-bromo-6-nitroquipazine and 6-bromoquipazine were very potent and selective inhibitors of 5-HT uptake in vitro, very close to that of 6-nitroquipazine. Furthermore, 4-bromo-6-nitroquipazine was about a 2-fold more potent inhibitor of specific binding of [3H]6-nitroquipazine in vivo in the hypothalamus of mouse brain than 6-bromoquipazine. Thus, 4-bromo-6-nitroquipazine seems to be superior to 6-bromoquipazine, as a potential ligand for in vivo imaging of 5-HT uptake sites in the brain. PMID- 1436392 TI - Influence of repeated treatment with buspirone on central 5-hydroxytryptamine and dopamine synthesis. AB - The anxiolytic agent buspirone was administered subcutaneously twice a day for 10 days to Sprague-Dawley rats, at a dose of 3 mg kg-1. Controls were given saline. On the eleventh day, the rats were given an injection of NSD-1015, an aromatic L amino acid decarboxylase inhibitor, 30 min before decapitation. To another group of rats, only one injection of buspirone was given, followed 30 min later by NSD 1015. After a further 30 min the animals were decapitated. The brains were rapidly removed and the raphe nuclei, striatum, hippocampus and cerebellum were dissected out on to dry ice. With the use of HPLC, the four regions of the brain were assayed for 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine, reflecting the synthesis of 5-HT and dopamine, respectively. In those rats which had received an acute dose of buspirone, the synthesis of 5-HT was substantially reduced in all four regions of the brain. However, in those rats which had received buspirone for 10 days, no such alterations in the synthesis of 5-HT were observed. The synthesis of dopamine was unchanged in any of the regions of the brain, after the acute dose of buspirone. After 10 days of treatment with buspirone, however, the synthesis of dopamine in the striatum was significantly reduced. These findings suggest that repeated treatment with buspirone reduces the synthesis of dopamine in the striatum but that the synthesis of 5-HT is unaffected. PMID- 1436395 TI - Effect of escalating doses of d-fenfluramine on the content of indoles in brain. AB - The neurochemical effects of a large dose challenge (5 mg/kg, i.p.) of d fenfluramine (d-F) in rats, given saline or gradually escalating doses of d-F (0.1-2.5 mg/kg, i.p.), were examined with regard to regional sensitivity and the time-course of recovery. The indole-depleting effect after the large dose of d-F to saline-pretreated animals appeared to differ, depending on the areas of brain considered (cortex greater than hippocampus greater than striatum), despite the fact that the drug and its main metabolite, d-norfenfluramine (d-NF) distributed almost uniformly in the regions of brain examined. The depletion in all these regions of the brain was reversible within 6 weeks, serotonin (5-HT) and 5 hydroxyindoleacetic acid (5-HIAA) being back to control levels in the hippocampus and striatum but not 5-HT in the cortex. However, when rats were exposed to gradually escalating doses of d-F the recovery of indoles in the brain, after injection of the large dose challenge, appeared to be faster. Indoles were markedly less reduced 1 week later in the cortex, hippocampus and striatum, with content of indole in the striatum showing complete recovery and the long-term depletion of 5-HT and 5-HIAA, by the subsequent large dose challenge was almost completely reversed in all regions. Analysis of the concentrations of d-F and its main metabolite d-fenfluramine (d-NF) in brain excluded any pharmacokinetic tolerance. These results suggest that during therapeutic treatment with d-F, the use of escalating doses may attenuate the potential for the long-lasting decrease of 5-HT in brain. PMID- 1436396 TI - Gliotoxic actions of excitatory amino acids. AB - Cultures of neonatal Type I astrocytes of the rat were exposed to a series of excitatory amino acid analogs to identify those compounds that were gliotoxic. In addition to L-alpha-aminoadipate, a previously identified gliotoxin, L homocysteate, L-serine-O-sulfate, L-alpha-amino-4-phosphonobutyrate and L-alpha amino-3-phosphono-propionate were also found to induce a sequence of degenerative events that led to the lysis of the astrocytes. Cellular injury was assessed by quantifying the activity of lactate dehydrogenase present in the surviving astrocytes. Prior to lysis, the cells went through a succession of distinctive morphological changes, the most prominent of which involved nuclear alterations. The nuclei appeared swollen, contained "pale" or "watery" nucleoplasm and exhibited a very prominent nuclear membrane and obvious nucleoli. These astrocytes appeared quite similar in appearance to the Alzheimer's Type II astrocytes, principally associated with the pathology of hepatic encephalopathy. The nuclear anomalies, which are thought to be indicative of cellular damage and compromised function, were also produced by the endogenous transmitters L glutamate and L-aspartate, although with time, the affected astrocytes appeared to recover and return to normal morphology, without lyzing. These findings suggest that excessive levels of excitatory amino acids may induce cellular damage to astrocytes, as well as neurons. Once damaged, the resulting reductions in astrocyte function may further contribute to CNS losses and the overall pathology attributed to the excitatory amino acids. PMID- 1436397 TI - Nicotine-induced depolarization of cerebral cortical synaptosomes is dependent upon sodium. AB - Earlier studies from this laboratory demonstrated that activation of nicotinic cholinergic receptors of cerebral cortical synaptosomes of the rat produced a decrease in the accumulation of [3H]tetraphenylphosphonium ([3H]TPP+) as a result of a decreased synaptosomal membrane potential. In the present study, the role of sodium in the effect of nicotine on the accumulation of [3H]TPP+ and the estimated potential difference was explored. Replacement of buffer sodium with either sucrose or N-methyl-D-glucamine (NMDG), attenuated the depolarization produced by the sodium channel activator, veratridine and had no effect on potassium-induced depolarization. The effect of nicotine on accumulation of [3H]TPP+ into cerebral cortical synaptosomes was abolished in sucrose buffer and attenuated in NMDG buffer. 1,1-Dimethyl-4-phenylpiperazinium iodide (DMP; 30 microM) produced a small increase in the influx of 22Na+ into cerebral cortical synaptosomes. The effect of DMPP on the influx of 22 Na+ was not blocked by tetrodotoxin. These results support the hypothesis that the nicotinic cholinergic receptor in the brain, functions as a sodium ionophore and further demonstrate that accumulation of synaptosomal [3H]TPP+ provides a simple tool with which to assess the effect of nicotine on sodium permeability through open nicotinic cholinergic receptor ionophores. PMID- 1436398 TI - Involvement of cholinergic mechanisms in impairment of working memory in rats following basolateral amygdaloid lesions. AB - In order to clarify the role of the amygdala in the working and reference memory of rats in the three-panel runway task, the effects of lesions of subnuclei of the amygdaloid complex on this behavior were studied. Rats that had been trained preoperatively, until they achieved the criterion of learning, were subjected to lesions of the amygdala. In the working memory task, lesions of the basolateral subdivision of the amygdala caused a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points), while lesions of the corticomedial amygdala had no effect on working memory errors. The increase in working errors, observed in basolateral amygdaloid-lesioned rats, declined gradually as retraining sessions were given once each day, reverting to control levels on and after the sixth session. In the reference memory task, the number of errors was not affected by lesions of the basolateral or corticomedial amygdala. The increase in working memory errors, induced by lesions of the basolateral amygdala was significantly reduced by intraperitoneal administration of the inhibitors of cholinesterase, tetrahydroaminoacridine (0.32-1.0 mg/kg) and physostigmine (0.032-0.1 mg/kg), and the muscarinic receptor agonist, oxotremorine (0.1 mg/kg), before the runway test. These findings suggest that the basolateral amygdala is selectively involved in working memory but not in reference memory and that the lowering of central cholinergic function may account for the impairment of working memory, induced by lesions of the basolateral amygdala. PMID- 1436399 TI - Central cardiovascular effects of physostigmine in anesthetized cats. AB - The central cardiovascular effects of a cholinesterase inhibitor, physostigmine, were studied in alpha-chloralose- and urethane-anesthetized cats, to determine the underlying site and mechanism of action. Intravenous injection of physostigmine produced a dose-dependent fall in blood pressure and heart rate. These responses were blocked by intravenous injection of atropine; however, the peripheral antimuscarinic agent, methscopolamine, failed to inhibit the depressor response. In decerebrated cats, physostigmine elicited similar responses in blood pressure and heart rate as in intact animals. In spinal cats, physostigmine failed to evoke any response. Physostigmine significantly reduced sympathetic nervous activity, as measured by renal sympathetic nerve discharges, indicating that the fall in blood pressure was due to a decrease in sympathetic tone. These results demonstrate that physostigmine, which crosses the blood-brain barrier, produces a depressor response through stimulation of muscarinic cholinergic receptors, located in the medullary region and that the effect is mediated by a decrease in sympathetic activity. PMID- 1436400 TI - Electrophysiological correlates for antinociceptive effects of histamine after intracerebral administration to the rat. AB - Data have been collected indicating possible functions for histamine in brain but there are only a very few data, collected exclusively with behavioural tests, about the effects of histamine on the perception of the pain, an important aspect in the homeostasis of the human body. The purpose of the present study was to investigate the effects of histamine, injected directly into the lateral cerebral ventriculi on the firing of nociceptive thalamic neurones, detected by electrophysiological techniques in rats rendered arthritic by injection of Freund's adjuvant into the left hindfoot. The noxious test stimuli used were either extension or flexion of the ankle or mild lateral pressure on the heel. With increasing doses of histamine (5, 10, 20, 40 micrograms) it was possible to observe an increasing inhibitory and long-lasting effects of the evoked activity, with a significant dose-effect linear regression. The inhibitory responses, induced by histamine, probably by a hyperpolarization phenomenon that decreased excitatory postsynaptic potentials, were clues for the presence of a histaminergic pathway in parallel with and/or in connection with other adrenergic, gabaergic, serotoninergic and opioidoergic pathways that regulate the transmission and the modulation of algogenic electrophysiological messages. PMID- 1436401 TI - Mechanisms of spinal reflex depressant effects of CS-722, a newly synthesized centrally acting muscle relaxant, in spinal rats. AB - The mechanisms of the depressant action of (R)-4-chloro-2-(2-hydroxy-3 morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized centrally acting muscle relaxant, on spinal reflexes were investigated in spinal rats. The drug CS-722 (50 mg/kg, i.v.) depressed the polysynaptic reflex but was less effective on the monosynaptic reflex. Eperisone HCl (10 mg/kg, i.v.) and baclofen (2 mg/kg, i.v.) markedly decreased the monosynaptic and polysynaptic reflexes, with longer durations than CS-722; CS 722, eperisone and baclofen depressed the dorsal root reflex. The excitability of the motoneurone was reduced by CS-722 and eperisone. Excitability of the primary afferent fibres was reduced by CS-722, while eperisone and baclofen had no effect. Both CS-722 and eperisone did not have a depressant influence on the focal synaptic potential. These results suggest that CS-722 and eperisone but not baclofen, have a common motoneurone-membrane-stabilizing action and that this action may contribute, in part, to the spinal reflex depressant effects of CS-722 and eperisone. PMID- 1436402 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1436403 TI - Behavioral effects of atriopeptin in rats. AB - High densities of atriopeptin-immunoreactive fibers and of highly specific and selective atriopeptin receptor sites are present in brain areas involved in animal behavior. The possible influence of these peptides on behavior was thus investigated in adult rats. The intracerebroventricular injection of atriopeptin II modified male sexual behavior (reduction in mount latency) at the dose of 5 micrograms/animal; lower and higher doses were ineffective. Open-field behavior was also modified by i.c.v. atriopeptin II at the doses of 5 and 10 micrograms/rat, which induced an increase in the number of external and internal crossings and of external rearings. Finally, in fasted rats, atriopeptin II, at the dose of 10 micrograms/rat, significantly increased the amount of food intake 30 and 60 min after injection. These findings indicate that atriopeptins may modify different animal behaviors. PMID- 1436404 TI - Neurotensin increases extracellular striatal dopamine levels in vivo. AB - This study employed intracranial microdialysis to assess the effects of neurotensin (NT) infusion on extracellular dopamine (DA) and DA metabolite concentrations in the rat striatum and nucleus accumbens, and the effects of NT on alterations in extracellular DA levels induced by cocaine and the DA D-2 receptor agonist, quinpirole. Direct NT infusion (.10, 1.0, 10.0 microM) did not significantly affect extracellular DA in the nucleus accumbens, but did produce a significant increase in the DA metabolite homovanillic acid (HVA). In contrast, direct NT infusion produced an increase in striatal DA levels, without altering DA metabolites. Neurotensin infusion (.10 microM) into the striatum significantly attenuated the peak DA increase induced by an intraperitoneal (IP) injection of a low dose (10.0 mg/kg) but not a high dose (30.0 mg/kg) of cocaine. Neurotensin infusion (.10 microM) did not affect the decrease in DA and its metabolites induced by an IP injection of a low dose of quinpirole (.03 mg/kg), but did alter the decrease in HVA induced by a high dose of quinpirole (.10 mg/kg). These results suggest that NT differentially affects in vivo DA release in the striatum and nucleus accumbens, and further strengthens the assertion that NT is an important modulator of dopaminergic function. PMID- 1436405 TI - Neuropeptide Y-containing interneurons in the hippocampus receive synaptic input from median raphe and GABAergic septal afferents. AB - Neuropeptide Y has been extensively studied in the central nervous system due to a possible involvement of neuropeptide Y-containing neurons in cognitive functions. In the hippocampus neuropeptide Y is present in a subpopulation of nonpyramidal cells, which control the firing of hippocampal output neurons. In the present study we examined whether septohippocampal and raphe-hippocampal afferents--known to have a powerful effect on hippocampal electrical activity patterns--innervate neuropeptide Y-containing neurons in the hippocampal formation of the rat. Using a combination of pre- and postembedding immunostaining and tracing with Phaseolus vulgaris leucoagglutinin (PHAL) we showed that GABAergic afferents arising from the medial septal area extensively innervate neuropeptide Y-containing neurons. Afferents of median raphe origin, most of which are thought to be serotonergic, were also found to make multiple synaptic contacts with these cells. Thus, the neuropeptide Y-containing subpopulation of interneurons--which innervate distal dendrites of principal cells--are also among those through which different subcortical nuclei modulate information processing in the hippocampal formation. PMID- 1436406 TI - Microsurgical removal of petroclival meningiomas: a report of 33 patients. AB - This is a report of 33 consecutive cases of petroclival meningioma treated surgically at our institution over the last 10 years; there were 21 women and 12 men between the ages of 27 and 68 (mean age, 52). All patients were assessed by computed tomographic scans including coronal sections and bone algorithm studies; in most cases, digital subtraction angiography and magnetic resonance imaging were also done. The largest tumor diameter was between 2 and 3.5 cm in 14 cases, 3.5 to 6 cm in 15 cases, and over 6 cm in 4 cases. Dural attachment predominantly involved the clivus and apical petrous bone on one side only; in 14 cases, however, the tumor grew over the clivus midline or crossed the tentorial notch. Cranial nerve deficit was extant in all cases and was commensurate with tumor size. Cerebellar signs and somatic motor deficits were present in 60 and 30% of cases, respectively. The surgical approaches used were the retromastoid retrosigmoid in 23 cases, subtemporal in 5 cases, and combined retromastoid subtemporal presigmoid in the remaining 5. Total removal was achieved in 26 cases (79%); incomplete removal occurred in 7 cases (21%). The extent of tumor removal and operative morbidity were not significantly related to tumor size. Brain stem indentation, arterial and cranial nerve encasement, and epidural invasion were the main factors that prevented total tumor removal and influenced operative morbidity. There was no intraoperative mortality, but three patients (9%) died perioperatively. In the postoperative period, most patients went through momentary neurological deterioration, chiefly due to new cranial nerve deficits. The average follow-up was 4.3 years in 27 patients; of these 17 were unchanged and 10 were improved. Before surgery, only 13 patients were self-sufficient; at long-term follow-up, another 6 had achieved independence. Our experience suggests that, even though real petroclival meningiomas still represent a formidable surgical challenge, such tumors can in most cases be removed completely with low attendant mortality and acceptable morbidity. PMID- 1436407 TI - Tumor control after stereotactic radiosurgery in neurofibromatosis patients with bilateral acoustic tumors. AB - During a 4-year interval, 17 patients with bilateral acoustic tumors (vestibular schwannomas) underwent unilateral stereotactic radiosurgery using a multisource gamma unit; 2 patients underwent radiosurgery of both tumors in separate sessions. Eleven patients with unoperated contralateral tumors served as concurrent controls to compare the effects of radiosurgery with the natural history of acoustic tumors. After radiosurgery, the tumor control and regression rates were 89.5 and 21.1%, respectively (median neuroimaging follow-up, 1.4 years; range, 0.3-3.9). The tumor regression rate increased to 40% for patients evaluated at least 12 months after radiosurgery. In comparison to the unoperated contralateral tumors, stereotactic radiosurgery achieved tumor control, as assessed by the ultimate change in tumor size at follow-up (P, 0.012), the change in tumor size over time (P, 0.006), and tumor growth rates (P, 0.003). This study provided convincing evidence that tumor stabilization after radiosurgery (as assessed by neuroimaging) truly represented tumor control. The incidence of delayed facial neuropathy after radiosurgery compared favorably with the incidence reported after microsurgical removal. Some hearing was preserved in one third of the patients who had preoperative hearing, including three patients who were contralaterally deaf. Stereotactic radiosurgery should be considered as a primary surgical modality for many patients with neurofibromatosis Type II. PMID- 1436408 TI - Flow cytometric analysis of deoxyribonucleic acid ploidy and proliferation in choroid plexus tumors. AB - The deoxyribonucleic acid (DNA) content of 10 choroid plexus tumors, including 4 malignant tumors and 3 normal choroid plexus controls, was analyzed by flow cytometry to determine whether a ploidy or proliferation rate is a better predictor of tumor behavior than histological features. Nine of 10 neoplasms had both diploid and aneuploid modal populations. One neoplasm and all three control cases had only a diploid peak. Among the tumors, the DNA indices of the aneuploid peaks ranged from 1.1 to 2.2. The percentage of aneuploid cells ranged from 7 to 99, and no distinction was made between benign and malignant. Proliferation rates were estimated from the combined S-phase fractions (SPF). The mean SPF of the control group was 0.7% +/- 0.15% SD. The mean SPF of the benign tumors (1.1 +/- 0.82% SD) was significantly different from the malignant group (7.0 +/- 1.25% SD; range, 5.3 to 8.6%) P = 0.0095. Low SPF fractions always correlated with favorable outcome. Higher proliferation rates were generally associated with an aggressive course. Evaluation of proliferation rates may help predict the behavior of choroid plexus tumors, particularly when histological features are equivocal. Measurement of DNA ploidy does not appear to have a role in the evaluation of choroid plexus tumors. PMID- 1436409 TI - Diffuse arteriovenous malformations: a clinical, radiological, and pathological description. AB - In a review of our series of patients with arteriovenous malformations (AVMs), a group with atypical angiographic and histopathological characteristics was discovered. Unlike the typical AVM, these lesions contained normal cerebral tissue between the abnormal vessels. We call these lesions diffuse AVMs, and think that this AVM represents one end of the AVM spectrum from a tight nidus to a diffuse lesion. The mean age of these patients was 18.1 years. Eight patients presented with an intracerebral hemorrhage, two with seizures, one with headache without hemorrhage, and one with ischemic symptoms compatible with vascular steal. Cerebral angiography revealed three AVMs to be 2 to 4 cm in diameter, four were 4 to 6 cm in diameter, and five were > 6 cm in diameter. Characteristic angiographic features included multiple small arterial feeders, small ectatic vessels in the malformation itself, multiple small draining veins, and a diffuse, puddling appearance of the contrast dye. Despite 16 operations in 11 patients, complete resection of the AVM was accomplished in only 8. The four patients with residual disease have received radiation therapy. Histopathology of the surgical specimens found AVM vessels interspersed among normal appearing neurons and white matter. Leptomeningeal angiodysplasia was noted when the cerebral cortex was involved. Gliosis was noted in some cases. Diffuse AVMs represent a difficult surgical challenge and recognition of the lesion aids in surgical planning. PMID- 1436410 TI - Children with cerebral venous thrombosis diagnosed with magnetic resonance imaging and magnetic resonance angiography. AB - From 1985 to 1991, 13 children were diagnosed at the University of Illinois College of Medicine at Peoria, Saint Francis Medical Center, with cerebral venous thrombosis (CVT) by magnetic resonance imaging scan. Ages ranged from newborn to 5 years. Six children were premature neonates, five were term neonates and two were 5 years old. In the premature neonates, thrombosis was usually associated with other problems. All the term neonates had seizures. In all neonates, thrombosis resolved without any specific treatment. In the two older children, one presented with pseudotumor cerebri and one with coma. These children required neurosurgical intervention. Follow-up magnetic resonance imaging scans were obtained in 9 of 13 children and showed thrombus resolution in each case. Three children were studied in the acute and convalescent stages by magnetic resonance angiography using time-of-flight techniques. Each follow-up magnetic resonance angiogram showed improvement in venous flow consistent with their clinical course and other imaging studies. We conclude that 1) CVT in children encompasses a range of clinical conditions which may or may not require neurosurgical intervention; 2) magnetic resonance imaging is superior to other modalities for the diagnosis of CVT; and 3) magnetic resonance angiography is an alternative means to monitor the evolution of CVT and efficacy of therapeutic intervention. PMID- 1436411 TI - Hemodynamic effects of preoperative embolization in cerebral arteriovenous malformations: evaluation with transcranial Doppler sonography. AB - A series of 83 patients with cerebral arteriovenous malformations is presented. All patients were evaluated with transcranial Doppler sonography. Thirty-two patients were treated with staged embolization and surgery: 19 of these patients were operated on within 4 weeks of the last embolization, and the remaining 13 patients underwent surgery 6 months or more from embolization. Transcranial Doppler sonography performed 1 day after embolization showed a significant (> 60%) reduction of main feeder flow velocity in 72% of patients after the first embolization and in 45% of patients after the second embolization. In no case did such a significant reduction occur after the third embolization. A flow redistribution in the basal vessels (defined as an increase in flow velocity of at least 30% of the initial value) occurred only in patients after the first embolization (64%). On delayed post-embolization studies, complete recovery of flow velocity in the embolized vessel occurred in 46% of patients, and sonographic recruitment of new feeders occurred in the remaining 54%. When main feeder flow velocity (mean) was higher than 120 cm/s after embolization and before surgery, the incidence of postoperative hyperemic complications (cerebral edema and/or intracerebral hematoma) was significantly higher than in patients with a mean flow velocity under 120 cm/s. It is concluded that transcranial Doppler sonography is a valuable method for a noninvasive hemodynamic assessment of shunt flow in arteriovenous malformations, and it permits a physiological monitoring of hemodynamic changes after embolization and allows more precise indications regarding further stages of embolization and timing of surgery after embolization. PMID- 1436412 TI - The Maudsley Mentation test: a method for extended monitoring of mental status after aneurysmal subarachnoid hemorrhage. AB - A new scale for the repeated, rapid assessment of mental function in patients with subarachnoid hemorrhage is described. Its reproducibility is evaluated and early experience with its use in the intended clinical setting is reported. The test (Maudsley Mentation Test) proved to be more sensitive to fluctuations in cerebral functioning than existing measures of conscious level, and the results were reproducible among observers with different backgrounds (surgeons, nurses, and psychologists). The results suggest a relationship between performance on mentation testing and quality of outcome. The Maudsley Mentation Test is thought to offer a suitable measure with which to monitor patients during the acute phase of their illness to supplement clinical assessment and provide evidence of deterioration at an early stage. It is also potentially useful as an end point in acute protection and treatment studies. PMID- 1436413 TI - Total intravenous anesthesia for improvement of intraoperative monitoring of somatosensory evoked potentials during aneurysm surgery. AB - Two anesthetic regimens for monitoring somatosensory evoked potentials (SEPs) during intracranial aneurysm surgery were compared. Eighty-four sequential cases of intracranial aneurysms were operated on employing SEP monitoring. The first group of 22 cases was anesthetized with "balanced anesthesia" and the second group of 62 cases received total intravenous anesthesia (TIVA) consisting of propofol and alfentanil. In the TIVA group, the amplitude of early cortical SEP responses (N20-P25, or P40-N50) was significantly higher than that of responses in the balanced anesthesia group. In median nerve SEPs, the averaged amplitude of N20-P25 was 3.22 microV with TIVA and 1.69 microV with balanced anesthesia (P = 0.006). Similarly, posterior tibial nerve SEPs showed a P40-N50 response of 1.85 microV and 1.00 microV, respectively (P = 0.017). The superior signal-to-noise ratio obtained with TIVA allowed more frequent and reliable intraoperative SEP recordings than was possible with balanced anesthesia, resulting in rapid and reliable feedback for the surgeon. In 19% of median nerve SEPs recorded with TIVA, the cortical responses were over 5 microV in amplitude, so that reproducible N20-P25 responses were obtainable by averaging only 10 to 50 serial responses, that is, two to three recordings per minute. The higher amplitude of posterior tibial nerve SEPs recorded with TIVA made monitoring during surgery for anterior communicating artery aneurysms possible in all cases. This was not always the case with balanced anesthesia. The late deflection of median nerve SEPs (N30) was more frequently observed with TIVA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436414 TI - Continuous-pressure controlled, external ventricular drainage for treatment of acute hydrocephalus--evaluation of risk factors. AB - Experience with a continuous-pressure controlled, external ventricular drainage system (EVD) in 100 patients (n = 49 female, n = 51 male; mean age, 56.3 yr) with acute hydrocephalus is reported. Cerebrospinal fluid circulation disturbances resulted from hemorrhages caused by subarachnoid hemorrhage (n = 45), parenchymal hemorrhages from angioma (n = 4), anticoagulants (n = 7), or hypertension or other reasons (n = 30); in addition, hydrocephalus developed from infections (n = 3), tumors (n = 2), infratentorial infarction (n = 5), or unknown reasons (n = 4); 52 patients had ventricular hemorrhages. No patient died of system-associated morbidity. Mean time of EVD treatment was 9.5 days, with 40 patients being treated for 10 to 29 days; routine refobacin (5 mg) flushing of the system was performed three times a day. Patients without cerebrospinal fluid leakage had a 2% rate of secondary infection compared with 13% in patients with cerebrospinal fluid leakage due to ventricular catheter placement (P < 0.05; overall infection rate, 5%). A clinical mortality rate of 29% during EVD treatment was observed in subarachnoid hemorrhage patients (Hunt and Hess Grades II, III, IV, and V; n = 9, 9, 18, and 9, respectively); recurrent hemorrhages during EVD treatment occurred in 19 patients (26 hemorrhages), and of these, 10 patients died. System occlusion was seen in 19 cases (12 of 45 patients with subarachnoid hemorrhage), requiring catheter and system renewal in 1 case; system extraction was seen in 3 cases, misplacement was seen in 11 cases, and disconnection was seen in 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436415 TI - Penetrating stab wounds to the brain: the timing of angiography in patients presenting with the weapon already removed. AB - Angiography is always necessary in patients with penetrating stab wounds to the head, to exclude unexpected vascular lesions. The most important, since they are seldom clinically evident, are traumatic aneurysms and arteriovenous fistulae. It has previously been proposed that carotid angiography should be delayed until the start of the second week, to allow for better visualization of these complications. However, traumatic aneurysms can rupture at any time after the injury, and the mortality resulting from a second hemorrhage is unacceptably high. A prospective study was undertaken in which 330 patients with penetrating stab wounds to the head underwent angiography as soon as possible after admission. In 250 of these patients (76%), the weapon had already been removed by the assailant, and there was radiological evidence of penetration of the dura. Of these 250, 130 patients underwent angiography within 7 days of the injury. Another 51 patients, who presented late, underwent angiography more than 7 days after the injury. The timing of angiography did not affect the identification of traumatic aneurysms, the incidence of which was 12% in both groups. Of the patients with cranial stabs and who required urgent evacuation of intracerebral hematomas, 10% had traumatic aneurysms that could be dealt with simultaneously. No patient in this series suffered a secondary hemorrhage. We conclude that it is neither necessary nor safe to delay angiography. In some patients, either because of vasospasm or "cut-off" of a vessel, a second angiogram may be necessary to further elucidate a vascular abnormality that might not have been evident originally. PMID- 1436416 TI - Syringomyelia in Chiari malformation: relation to extent of cerebellar tissue herniation. AB - In 47 patients with Chiari malformations (41 with Type I, 6 with Type II) diagnosed by magnetic resonance imaging, syringomyelia was found significantly more frequently in those who had a herniation of 9 to 14 mm (9 of 16, 56%) than in those who had a smaller (2 of 15, 13%) or larger (2 of 16, 13%) herniation. Syringomyelia associated with the Chiari malformation is generally considered to be due to mechanical factors induced by altered cerebrospinal fluid hydrodynamics. On the basis of the present study, one may speculate whether these mechanical factors affect the cord most efficiently at an intermediate level of herniation, which may prove to be a risk factor for the development of syringomyelia. PMID- 1436417 TI - Monitoring of brain tissue pressure with a fiberoptic device. AB - Continuous monitoring of brain tissue pressure can now be achieved with intracerebral placement of fiberoptic microtransducers. This study was undertaken to test the safety, accuracy, and reliability of this relatively new type of intracranial pressure (ICP) monitoring. Initially, the fiberoptic device was compared with a concurrently functioning intraventricular catheter in 18 patients. The results from the two methods corresponded closely over a wide range of pressures, and the correlation coefficient approached 1.0. Subsequently, this monitor was used for routine measurement of ICP in a series of almost 200 neurosurgical patients at risk of intracranial hypertension. The tracings showed good wave forms and consistent absolute values of ICP. No instances of hemorrhage, mechanical failure, or other complications were associated with this monitor, except one case of infection, which was not directly attributable to the device per se. When bilateral intraparenchymal pressures were recorded in patients with unilateral mass lesions, significant transitory pressure differentials between the ipsilateral and contralateral sides were documented. It is concluded that monitoring intraparenchymal pressure with the fiberoptic device offers safe and reliable ICP recordings for routine neurosurgical practice. In patients with unilateral masses, ICP should be measured in close proximity to the lesion. PMID- 1436418 TI - Protection of iodine-125 brachytherapy brain injury in the rat with the 21 aminosteroid U-74389F. AB - Radiation protection was studied in a rat brachytherapy brain injury model. Radiation lesions were produced by stereotactic placement of high-activity iodine 125 seeds on the frontal lobe of F-344 rats. A minimum dose of 80 Gy was delivered to a 5.5-mm-radius volume. Radiation damage was evaluated 24 h after removal of the seeds by T1-weighted gadolinium-enhanced magnetic resonance imaging on a 1.5-T unit. Computerized three-dimensional reconstruction of the lesions seen on magnetic resonance imaging was performed to calculate the volume of radiation injury. Two experiments were performed with rats of different weights (mean, 300 g; mean, 180 g). All animals underwent surgical placement of an indwelling internal jugular catheter before brachytherapy. Treated animals received the 21-aminosteroid U-74389F 5 mg/kg intravenously every 6 hours during the implant and for 24 hours after the removal of the iodine-125 seed. Control animals were administered vehicle only. In both experiments, a statistically significant reduction in volume of radiation damage was observed in the U-74389F treated group compared with the control group. PMID- 1436419 TI - The effect of the 21-aminosteroid U74006F in a rabbit model of thromboembolic stroke. AB - U74006F, a novel 21-aminosteroid, is an inhibitor of iron-dependent lipid peroxidation that is devoid of glucocorticoid and mineralocorticoid side effects. The efficacy of U74006F in reducing cerebral infarct size was investigated in a rabbit model of thromboembolic stroke. Each animal received either U74006F (3.0 mg/kg immediately before and 2 hr after embolization, n = 8) or vehicle control (n = 10). Hematocrit, mean arterial pressure, PCO2, PO2, and pH were measured and controlled both before and after the administration of an autologous clot into one internal carotid artery. Regional cerebral blood flow (in ml/100 g/min, mean +/- SEM) measured by hydrogen clearance was similar in both groups, being reduced from 68.2 +/- 9.6 to 5.2 +/- 1.9 in the control group immediately after clot embolization and from 73.3 +/- 14.9 to 7.0 +/- 1.7 in the U74006F group. Four hours after embolization the brain was harvested and cerebral infarct size was determined using the triphenyl-tetrazolium chloride technique (% hemisphere, mean +/- SEM). In the U74006F-treated group, the infarct size was significantly reduced (P < 0.05) to 14.8 +/- 6.4 from a control value of 36.0 +/- 6.4. Additionally, cerebral blood flow values after embolization were consistently higher in the U74006F group, although the differences were not statistically significant. This data suggests that the 21-aminosteroid U74006F may have a protective effect in cerebral ischemia. PMID- 1436420 TI - Regional changes in central nervous system thyrotropin-releasing hormone after pentylenetetrazol-induced seizures in dogs. AB - We have recently shown that seizures induce significant and sustained elevations of thyrotropin-releasing hormone (TRH) in specific extrahypothalamic rat brain regions associated with epileptic foci including amygdala, hippocampus, pyriform cortex, and anterior cortex. Seizures were induced in dogs to further study the effect on central nervous system TRH in a species known to show epileptiform seizures. Adult mongrel beagles were given pentylenetetrazol (PTZ) to induce generalized tonic-clonic seizures. Two groups of dogs were given either PTZ or saline every other day for four intravenous injections. Major motor seizures were observed visually and by electroencephalography with each PTZ injection, and these lasted from 3 to 10 minutes. Forty-eight hours after the fourth seizure, the dogs were killed and brains were removed, dissected, and stored at -90 degrees. After acetic acid extraction, extracts were assayed for TRH content by specific radioimmunoassay. Significant (P < 0.05) postictal TRH increases were seen in frontal cortex (1.5-fold), dorsal hippocampus (2.2-fold), pyriform cortex (2.5-fold), and amygdala (2.1-fold). Cerebellum, medulla, thalamus, hypothalamus, and septum showed no postictal changes in TRH. This report is the first to demonstrate TRH elevations in specific central nervous system regions associated with epileptic foci in the dog. Our results continue to stress the importance of the pyriform/periamygdaloid region as a key limbic region of endogenous TRH action in response to seizures and provides further evidence that TRH is either directly or indirectly involved in seizure modulation. Additional recent data from our laboratory and others suggest that this modulation is intrinsic to the hippocampus and may be anticonvulsant in nature. PMID- 1436421 TI - Gender distribution and sidedness of middle fossa arachnoid cysts: a review of cases diagnosed with computed imaging. AB - According to earlier reports, arachnoid cysts seem to occur more frequently in males, and on the left side. The latter phenomenon could, however, be explained by a greater significance attributed to symptoms from the dominant hemisphere as a justification for invasive procedures in the pre-computed tomography era. The literature from the last third of the era of computed tomography is reviewed with respect to gender distribution and sidedness for middle fossa arachnoid cysts. Also included are a few cases of our own from the same period. It is evident from this survey of the literature, based on computed tomography studies, that there is a significant tendency for these cysts to occur in males, with a male/female ratio of nearly 3:1. This preponderance toward males could not be explained by the somewhat higher frequency of associated subdural hematomas that was found in male patients. The survey also showed that middle fossa arachnoid cysts occur or are detected significantly more frequently on the left side than on the right, with a ratio of 1.8:1. PMID- 1436422 TI - Meningeal melanocytoma: diagnostic criteria for a rare lesion. AB - A case of meningeal melanocytoma, the 14th in the literature, is presented. Neurodiagnostic imaging, with both computed tomographic scan and magnetic resonance imaging, is included. Pathological examination of the tumor consisted of light microscopy, electron microscopy, and immunohistochemistry. The literature is reviewed and pathological criteria are presented to distinguish meningeal melanocytoma from meningiomas containing melanin pigment and from malignant melanoma. PMID- 1436423 TI - Metastatic carcinoid tumor to the orbit and brain. AB - Carcinoid tumors constitute an uncommon source of metastatic lesions to the brain. We report the case of a 63-year-old man who initially sought treatment for proptosis 15 years before coming to our attention with a metastatic intracerebral left parietal carcinoid. The pathological features of the exenterated orbital mass were interpreted as undifferentiated carcinoma, and a lesion of the left lower lobe of the lung that had been removed 6 years earlier had been reported as metastatic malignant melanoma. The long duration between the initial diagnosis and the onset of neurological symptoms brought into question the original diagnosis, which, in retrospect, was most consistent with metastatic carcinoid. Staining for cytokeratin, neuron-specific enolase, and synaptophysin in the absence of staining for S-100 and HMB-45 supported the revised pathological diagnosis. Metastatic intracerebral carcinoid from an unrecognized bronchogenic source is a rare event, particularly after an orbital metastasis, but should be suspected when the clinical course is inconsistent with the more common causes of metastatic disease. PMID- 1436424 TI - Chondrosarcoma of the temporal bone in an infant: case report and review of the literature. AB - Cranial chondrosarcomas are rare. The majority of cases arise from the base of the skull and are most common in adult life. In this report, an infant with a chondrosarcoma of the temporal bone is discussed. We are not aware of a previously reported case of chondrosarcoma of the temporal bone in this age group. PMID- 1436425 TI - Meningeal melanocytoma of the C8 nerve root: case report. AB - A case of a meningeal melanocytoma involving the C8 nerve root is presented. The clinical symptoms and the radiological investigations resembled a neurinoma of the spinal nerve root. Intraoperatively the tumor was seen to be firmly attached to the dural covering of the dorsal nerve root. By using microsurgical technique, complete removal of the tumor with preservation of the ventral nerve root was accomplished. Histological examination revealed a typical meningeal melanocytoma as described by Limas and Tio in 1972. Ten additional cases of previously reported spinal meningeal melanocytomas are reviewed. The importance of differentiating this benign lesion from meningeal malignant pigmented tumors is stressed. PMID- 1436426 TI - Ependymoma of the spinal nerve root: case report. AB - Ependymomas are the most common intramedullary tumor of the spinal cord. They are most common at the region of the cauda equina, accounting for up to 90% of primary tumors in that area. Extraspinal ependymomas are rare. We describe a case of an ependymoma arising in a spinal peripheral nerve root. PMID- 1436427 TI - Langerhans cell histiocytosis of the spine causing cord compression: case report. AB - A case of Langerhans cell histiocytosis of the spine causing myeloradiculopathy is reported. Almost complete regression of symptoms and signs was observed in the patient after surgical treatment and radiotherapy. The clinical and histological features of the disease are discussed. The literature dealing with the previously reported cases of spinal histiocytosis involving neural structures is reviewed. PMID- 1436428 TI - Anomalous muscle belly of the flexor digitorum superficialis associated with carpal tunnel syndrome: case report. AB - A patient had a 10-year history of pain and swelling in the right wrist and palm. Carpal tunnel exploration showed anomalous muscle bellies of flexor digitorum superficialis II and III. The muscle bellies were excised. Postoperatively, the symptoms disappeared. Our case is compared with others in the literature. PMID- 1436429 TI - Outcome measures for clinical trials involving traumatically brain-injured patients: report of a conference. AB - A conference was held in Houston, Texas, on October 8-9, 1991, to develop recommendations for outcome measures for clinical trials in traumatic brain injury. Participants, all experts in this area, discussed and agreed on treatments for patients with severe brain injury (Glasgow Coma Score [GCS] < or = 8) and moderate brain injury (GCS, 9-12). A parallel trial design was recommended rather than a factorial, sequential, or crossover design. It was agreed that stratifying randomization based on motor score alone or on a combination of motor score and age would result in increased power. Acute stage measurements, such as cerebral blood flow, cerebrospinal fluid biochemistry, and evoked potentials, were recommended only when they satisfied a specific hypothesis. Functional outcome measures were recommended as the primary outcome measure for severe brain injury (GCS, 3-8). Either the Glasgow Outcome Scale or Disability Rating Scale, measured at 6 months after injury, were recommended as the primary outcome measure for severe brain injury (GCS, < or = 8). For patients with moderately severe brain injury (GCS, 9-12), the Disability Rating Scale at 3 months after injury was recommended as the primary outcome measure. The Neurobehavioral Rating Scale appears to be a satisfactory instrument for measuring behavioral changes. Specific neuropsychological measures were recommended as supplementary outcome measures for both severe and moderate brain injury, consistent with a 1.5-hour period available for testing. PMID- 1436430 TI - Microvascular anatomy of the uncus and the parahippocampal gyrus. PMID- 1436431 TI - Partial callosal resection for pericallosal aneurysms. PMID- 1436432 TI - Skill learning and repetition priming in Alzheimer's disease. AB - While perceptual-motor learning occurs normally in Alzheimer's disease (AD) patients, their ability to acquire the skill of reading transformed text has not been well delineated. AD patients and matched controls were timed as they read two blocks of words presented in mirror image. Control subjects displayed both skill learning and repetition priming, whereas AD patients displayed only repetition priming. Skill learning in AD patients was associated with their ability to complete verbal analogies. They displayed the expected impairment in recognition for the words from the mirror reading task. The failure of AD patients to acquire the mirror reading skill can be understood through a task analysis and may reflect an underlying deficit in abstract reasoning that precludes the development of appropriate pattern analyzing strategies needed to transform rotated text. PMID- 1436433 TI - Effect of stimuli in right hemispace on left-sided neglect in a line cancellation task. AB - Twenty-seven patients with right cerebral infarcts resulting in left-sided neglect in a line cancellation task were also tested for line cancellation when the lines were confined to the left half of sheets. All but one patient (whose neglect in the former condition was minimal) were still impaired in the latter condition, a finding that indicates that hyperattraction to test stimuli in the unneglected (right) hemispace was not the crucial factor preventing them from completing the standard version of the cancellation task, although it may have played some role. The results are consistent with the conclusion that hyperattention to stimuli in the unneglected hemifield, and possibly to stimuli in the unneglected hemispace, together with other factors, could account for the patients' impairment in line cancellation. PMID- 1436434 TI - Judgements about numerosity by a commissurotomized subject. AB - A commissurotomized subject, L.B., was shown asterisks flashed at random locations, up to four in each field, and attempted either to compare the numbers in the two fields or to report the total number. The main results were: (a) Report was more accurate with unilateral than with bilateral presentation, suggesting that the difficulty integrating across fields was partly attentional; (b) in integrating across fields, attention was focused on one field, with only crude 'one-or-many' information from the other; (c) in cross-field comparisons, the focus was on the LVF, but in reporting the number it was on the RVF when report was oral or right-handed, and on the LVF when report was left-handed; (d) cross-field comparisons were improved when the locations were mirrored across the midline. PMID- 1436435 TI - Prehension movements directed to approaching objects: influence of stimulus velocity on the transport and the grasp components. AB - In this investigation we studied the influence of object velocity on the transport and on the grasp components of prehension movements directed to approaching objects. Three experiments were carried out. In the first experiment six subjects were required to reach and grasp a sphere that approached them with a constant velocity. The effects of four velocities were studied. The results showed that the end point of the arm movement changed with object velocity: nearer the body with higher than with lower object velocities. Transport velocity increased with movement amplitude and the deceleration phase decreased in duration with higher object velocities. On the contrary the grasp component was not affected by object velocity. The second experiment was a control experiment carried out in order to verify whether a possible influence of object velocity on the grasp could be revealed in an experimental condition in which grasp planning relies without doubt on visual computation of all object features. In this experiment object velocity and object size were randomly varied. The results showed that the grasp was not influenced by object velocity, whereas it was sensitive to changes of object size. The third experiment had the two-fold aim of establishing (1) whether transport velocity was influenced by object velocity once the location in space at which the object had to be grasped was fixed and (2) whether the grasp kinematics differed for prehension movements directed respectively to stationary or to moving objects. Results showed that the first part of the transport is affected only by distance, whereas the deceleration phase decreased with increasing object velocity. This last result suggests that subjects minimized object displacements in order to grasp the sphere correctly. The grasp component differed between the conditions of stationary and moving stimuli only in the relative timing between finger aperture and closure phases. The closure phase decreased in the condition of moving stimuli. The results of the three experiments indicate the dependence of transport parameters on object velocity, whereas grasp parameters appear to be unaffected. PMID- 1436436 TI - Acquisition and transfer of declarative and procedural knowledge by memory impaired patients: a computer data-entry task. AB - Previous research demonstrated that a single amnesic patient could acquire complex knowledge and processes required for the performance of a computer data entry task. The present study extends the earlier work to a larger group of brain damaged patients with memory disorders of varying severity and of various etiologies and with other accompanying cognitive deficits. All patients were able to learn both the data-entry procedures and the factual information associated with the task. Declarative knowledge was acquired by patients at a much slower rate than normal whereas procedural learning proceeded at approximately the same rate in patients and control subjects. Patients also showed evidence of transfer of declarative knowledge to the procedural task, as well as transfer of the data entry procedures across changes in materials. PMID- 1436437 TI - Assessment of attention and memory efficiency in persons with solvent neurotoxicity. AB - Memory and attention were evaluated in 40 persons with a history of organic solvent exposure and 40 demographically similar controls. Exposed subjects, in comparison to controls, had reduced digit spans, were deficient at learning new information, and recall on a Brown-Peterson distractor test was especially low following a 30-sec interference interval. If original learning was considered, long-term recall was similar for both groups. On a test of sustained attention, the Continuous Performance Test, exposed subjects became less accurate over successive blocks, a pattern opposite to that seen in control subjects. The data suggest that the memory impairment following solvent exposure may result from deficient allocation of attentional resources due to the inability to deal effectively with an increase in processing load. PMID- 1436438 TI - Interhemispheric interaction affected by computational complexity. AB - The present study investigated whether dividing information between the hemispheres becomes more advantageous to task performance as computational complexity increases. We hypothesized that interhemispheric processing would benefit performance especially for computationally complex tasks, whereas it would hinder performance for relatively simple ones. A letter-matching task was given to 23 subjects at three levels of computational complexity. Complexity was varied either by increasing the number of inputs to be processed or by the nature of the decision to be made. The results indicated that each of these manipulations of complexity influenced performance by making it more advantageous to have both hemispheres involved in processing rather than just one. Furthermore, the effects of each manipulation were separable. PMID- 1436439 TI - Intact implicit memory in patients with frontal lobe lesions. AB - Patients with frontal lobe lesions and control subjects were administered tests of word-stem completion priming. In this implicit memory test, subjects are first presented words (e.g. MOTEL, PARADE) in an incidental learning paradigm. Following word presentation, subjects are shown word stems (e.g. MOT, PAR) and asked to produce the first word that comes to mind. Patients with frontal lobe lesions exhibited normal levels of word-stem completion. These findings indicate that implicit memory can operate normally despite damage to the prefrontal cortex. The present results substantiate previous neuropsychological and positron emission tomography findings which indicate that word priming depends critically on posterior cortical areas. PMID- 1436440 TI - Peptidergic modulation of learning a motoric food-procuring conditioned reflex skill. AB - Experimental data are presented which were obtained during an investigation of the influence of various doses of a synthetic heptapeptide based on tafcine on the learning of a complex instrumental skill in dogs. The effectiveness of the intranasal application of the peptide in the early stages of learning was demonstrated, as was its capacity to restore the lost skill. The vegetative support of the motoric reactions during the modulation of the learning by the peptide was investigated. PMID- 1436442 TI - Active electrogenesis of command neurons of defense behavior of the snail during conditioning. AB - A change in the active electrogenesis of command neurons of the defensive closing of the spiracle of the edible snail during the development, extinction, and repeat development of a classical conditioned defense reflex in response to tactile stimulation is described in this study; the tactile stimulation of another point of the body served as the differential stimulus. As the biological significance of the conditional stimulus increased as the result of training, the excitability of the command neurons in response to this stimulus increased. At the same time, the neurons manifested reduced excitability in response to the differential stimulus. The possible mechanisms of the rapid reorganization of the excitability of the neurons and the functional significance of the change in the generation threshold of the AP are discussed. PMID- 1436441 TI - Dynamics of interstimulus intervals in the activity of neurons of the sensorimotor cortex during the development of a food-procuring reflex in the rabbit. AB - The impulse activity of neurons of the sensorimotor cortex (SMC) during the formation of a food-procuring reflex in the rabbit, as well as in trained animals if reinforcement is discontinued and substituted, was investigated. In the process of training the neurons of the SMC acquire the capacity for anticipatory reactions. The sudden abolition and substitution of reinforcement elicits the appearance of activity which is characteristic for the process of discordance in the acceptor of the result of the action. Repeated substitutions lead to the appearance of activity which is characterized by a coordination process at the moment of the "recognition" of the substitution, despite the absence of food reinforcement. PMID- 1436443 TI - Stimulated shift in the stability of heart rhythm as a condition of the activation of the CNS and perception of a stimulus. PMID- 1436444 TI - Irreversibility of disruptions of integrative activity induced by damage to the amygdala, with unilateral transplantation of embryonal amygdalar tissue. PMID- 1436445 TI - Structure and nature of macrophages participating in the wallerian degeneration of nerve fibers. AB - The posttraumatic processes of Wallerian degeneration of nerves have been illuminated in detail. The dynamics of the breakdown of axons and the myelin sheaths of nerve fibers has been established, as have been the periods of the changes in the composition of myelin, and the reactive changes in the Schwann cells and the connective tissue structures in the makeup of the nerve as well as the formation of "foam" cells have been described. The controversial questions which have been raised in these studies regarding the role of the cellular elements (the Schwann cells, the endoneurial fibroblasts, the cells of the epi- and perineurium) during Wallerian degeneration remain unresolved until the present time. In particular, the question as to which cells participate in the cleanup of the products of the breakdown of the myelin sheaths, and as to the character of the inflammatory infiltration in Wallerian degeneration and the degree of the participation of the various cellular elements in the destructive and reparative processes, has not been elucidated. Some investigators believe that the Schwann cells accomplish the cleanup of the products of the breakdown of the myelin sheaths. There are also data suggesting that the macrophages are of considerable significance in the cleanup of the products of the breakdown of nerve fibers of both the PNS and the CNS following their injury. It has been demonstrated by means of monoclonal antibodies to macrophages, radioautography, and immunocytochemical methods that these macrophages have a hematogenous origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436446 TI - Features of the behavioral reactions of rats during exposure to constant electrical fields of varied intensities. AB - The dynamics of the spontaneous orienting-motoric activity and the character of the formation and of the extinction of conditioned reflex reactions during food and painful reinforcement in rats following exposure to a constant electrical field (CEF) with an intensity of from 30 to 160 kV/m were studied. It was established that as the result of the exposure to a CEF of relatively low intensity, orienting activity intensifies, and the formation and the extinction of the conditioned avoidance reaction slow down. In the presence of the effect of a CEF of medium intensity, an increase in activity in the vertical plane correlates with the rapid formation of the defense reflex and the prolonged maintenance of the conditioned reactions developed. In the presence of a high intensity field the number of both horizontal and vertical locomotions decreases due to an increase in the proportion of static elements and grooming. The rate of formation of the conditioned reflexes with food and painful reinforcement slows sharply. PMID- 1436447 TI - Influence of pulse stimulation of the visual cortex on the function of the superior colliculus of the awake rabbit. AB - It has been demonstrated in awake rabbits that stimulation of the visual cortex by a solitary pulse of electrical current leads to the formation of a short latency response in the superior colliculus. The formation of this response is suppressed when a light stimulus precedes it. At the same time, a conditioning solitary electrostimulation of the visual cortex induces a short inhibition of the formation of the response to the test light stimulus. This fact suggests that the influences of the visual cortex on the functioning of the superior colliculus may be biphasic in character. When the adrenergic apparatus of the reticular formation is blocked this inhibitory influence bears a more pronounced and prolonged character. The stimulation of the reticular formation, on the other hand, by means of anodic polarization leads to the diametrically opposite effect: the inhibitory character of the influence of the cortex is replaced by a facilitatory one. The inference is drawn that the character and the directionality of the influence of the visual cortex on the functioning of the superior colliculus is determined to a significant degree by the initial functional state of nonspecific brain systems. PMID- 1436448 TI - A microdialysis investigation of the release of norepinephrine in the hypothalamus induced by 2-deoxyglucose in awake rats. AB - The level of norepinephrine in the extracellular space of the lateral hypothalamus was measured by means of intracerebral microdialysis in awake rats. The introduction of desipramine (10 mumole) into the perfusing medium did not affect the basal level of norepinephrine, but increased the release of norepinephrine during local K(+)-stimulation. Neuroglycopenia created under the influence of 500 mg/kg of 2-deoxyglucose induced a threefold increase in the level of norepinephrine in the extracellular space of the hypothalamus, which achieved a maximal value in the first 40 min following the introduction of the substance, and thereafter gradually decreased to the basal level. PMID- 1436449 TI - Clinical-physiological characteristics of syncopal states in a prolonged Q-T interval syndrome (Ward-Romano syndrome). PMID- 1436450 TI - Some neurophysiological aspects of the investigation of children with Gilles de la Tourette syndrome. PMID- 1436451 TI - Specificity of the neuropsychological syndromes of the disturbance of higher mental functions in Alzheimer's disease and senile dementia. PMID- 1436452 TI - Magnetic resonance imaging and histopathology of cerebral gliomas. AB - The correlation of magnetic resonance imaging (MRI) with histopathological findings was analysed in 26 patients with untreated cerebral gliomas. In low grade gliomas, T2-weighted images demonstrated relatively homogeneous high intensity lesions involving both the grey and the white matter. In high-grade gliomas, especially grade IV, T2-weighted images demonstrated prominent heterogeneity in signal intensity, which consisted of a hyperintense "core", less hyperintense or normal intensity "rim" and surrounding finger-like areas of high intensity. Marked and irregular contrast enhancement was evident in all but one case of these high-grade gliomas in which gadolinium-DTPA was used. Histological examination revealed tumour cells extending as far as the borders of the high intensity areas shown on T2-weighted images in both high- and low-grade gliomas, but in 5 of 8 low-grade and 4 of 18 high-grade gliomas, isolated tumour cells extended beyond the hyperintense areas shown on T2-weighted images. PMID- 1436453 TI - Volume measurement of multiple sclerosis lesions with magnetic resonance images. A preliminary study. AB - The ability to visualise multiple sclerosis lesions in vivo with magnetic resonance imaging suggests an important role in monitoring the course of the disease. In order to help the long-term assessment of prospective treatments, a semi-automated technique for measuring lesion volume has been developed to provide a quantitative index of disease progression. Results are presented from a preliminary study with a single patient and compared to measurements taken from lesion outlines traced by a neuroradiologist, two neurologists and a technician. The semi-automated technique achieved a precision of 6% compared to a range of 12 33% for the manual tracing method. It also reduced the human interaction time from at least 60 min to 15 min. PMID- 1436454 TI - Marchiafava-Bignami disease: serial changes in corpus callosum on MRI. AB - Serial MRI findings of changes in corpus callosum lesions in two cases of Marchiafava-Bignami disease are presented. In both, MRI displayed diffuse swelling of the corpus callosum in the acute stage, thought to represent oedema and demyelination. In the chronic stage, in addition to atrophy of the corpus callosum with presumed focal necrosis, previously undescribed focal hypointensity on T2-weighted images, of unknown cause, was observed in the corpus callosum. PMID- 1436455 TI - Tay-Sachs disease: progression of changes on neuroimaging in four cases. AB - The neuroradiological findings in four patients with Tay-Sachs disease are described in three phases of the clinical course. The basal ganglia and cerebral white matter show low density on computed tomography and high signal intensity on T2-weighted magnetic resonance imaging in the initial phase. The caudate nuclei are characteristically enlarged and protrude into the lateral ventricles in the first and second phases. The cerebral white matter shows low density on the CT which varies in extent from the second to third phases, and the whole brain becomes atrophic in the last phase. Thus, central nervous system involvement in the disease may begin in basal ganglia as well as in cerebral white matter. PMID- 1436456 TI - Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study. AB - Magnetic resonance imaging and a comprehensive cognitive evaluation were carried out in a series of 29 patients with mild to moderate Huntington's disease (HD). A factor analysis of the neuropsychological test scores provided three factors: a memory/speed-of-processing factor, a "frontal" factor, and a response inhibition factor. The memory/speed factor correlated significantly with measures of caudate atrophy, frontal atrophy, and atrophy of the left (but not the right) sylvian cistern. There were no significant correlations between the "frontal" or response inhibition factors and measures of cortical or subcortical brain atrophy. Our findings confirm that subcortical atrophy is significantly correlated with specific cognitive deficits in HD, and demonstrate that cortical atrophy also has important association with the cognitive deficits of patients with HD. PMID- 1436457 TI - MRI of herpes simplex encephalitis. AB - The magnetic resonance imaging (MRI) findings in eight patients with herpes simplex meningoencephalitis were reviewed: 14 examinations were analysed. The most striking finding was high signal intensity in the temporal lobe(s) with the typical configuration known from CT. Meningeal enhancement after Gd-DTPA administration was clearly seen in four patients. Haemorrhagic changes are much better seen on MRI than on CT. When adequate motion control can be achieved, MRI becomes the examination of choice in the diagnosis and follow-up of herpes simplex encephalitis. Localized 1H MR spectroscopy also proved promising in the study of neuronal loss. PMID- 1436458 TI - Isodense subdural haematomas on CT:MRI findings. AB - MRI findings are described in two patients with subdural haematomas isodense on CT. In one patient, admitted 6 weeks after trauma, a chronic subdural haematoma showed extreme hypointensity on T2-weighted images, suggesting acute trauma, and therefore acute rebleeding. In the second patient with severe anaemia, an acute subdural haematoma was hyperintense on T2-weighted images, suggesting chronic trauma; this may be explained by the low haematocrit and a possible mixture of blood with cerebrospinal fluid. The MRI features of subdural haematomas and hygromas have to be kept in mind, in order not to misjudge the age of the haematoma. PMID- 1436459 TI - Infarction in the territory of the anterior inferior cerebellar artery: report of five cases. AB - The clinical and MRI features were correlated in five cases of infarction in the territory of the anterior inferior cerebellar artery. The lateral portion of the pons area was affected in four cases, the middle cerebellar peduncle in two, and the cerebellar hemisphere in three. The lesion was restricted to the cerebellar hemisphere in one patient. In no case did the clinical features conform to the classical description. PMID- 1436460 TI - Retrograde filling of the anterior choroidal artery: vertebral angiographic sign of obstruction in the carotid system. AB - Retrograde filling of seven anterior choroidal arteries from the posterior circulation was observed on a vertebral angiogram in six patients with occlusion of the proximal anterior choroidal artery or of the internal carotid artery. In one patient with thrombotic occlusion of the internal carotid artery, the enlarged anterior choroidal artery functioned as a major collateral pathway from the posterior circulation to the territory of the middle cerebral artery. Retrograde filling of the anterior choroidal artery is a sign of obstruction changes in the ipsilateral carotid artery at or proximal to the origin of the anterior choroidal artery. PMID- 1436461 TI - Safety of the adjustable pressure ventricular valve in magnetic resonance imaging: problems and solutions. AB - We performed magnetic resonance imaging in 30 patients with hydrocephalus with Sophy adjustable pressure valves (PAVS). A pressure check following the MRI study showed a significant proportion with pressure valve changes, which could easily be readjusted by percutaneous manipulation. The value of the PAVS and its safety during MRI examinations are discussed. PMID- 1436462 TI - Cortical region of interest definition on SPECT brain images using X-ray CT registration. AB - We present a method for brain single photon emission computed tomography (SPECT) analysis based on individual registration of anatomical (CT) and functional (133Xe regional cerebral blood flow) images and on the definition of three dimensional functional regions of interest. Registration of CT and SPECT is performed through adjustment of CT-defined cortex limits to the SPECT image. Regions are defined by sectioning a cortical ribbon on the CT images, copied over the SPECT images and pooled through slices to give 3D cortical regions of interest. The proposed method shows good intra- and interobserver reproducibility (regional intraclass correlation coefficient approximately 0.98), and good accuracy in terms of repositioning (approximately 3.5 mm) as compared to the SPECT image resolution (14 mm). The method should be particularly useful for analysing SPECT studies when variations in brain anatomy (normal or abnormal) must be accounted for. PMID- 1436463 TI - Effects of radiotherapy determined by 11C-methyl-L-methionine positron emission tomography in patients with primary cerebral malignant lymphoma. AB - Two cases of histologically proven primary cerebral malignant lymphoma were examined serially with positron emission tomography (PET) using 11C-methyl-L methionine (11C Met). Lesions delineated by 11C Met accumulation extended beyond enhancing areas on either X-ray computed tomography (CT) or magnetic resonance imaging. High uptake of 11C Met accurately showed biologically active and residual tumours, at a time when disappearance of a contrast-enhancing lesion on CT seemed to indicate involution. PET provides valuable information on the extent of tumour and assessment of radiotherapy in malignant lymphoma. PMID- 1436464 TI - Aspergillosis of the paranasal sinuses. AB - The CT appearances of 13 cases of pathologically proven aspergillosis involving paranasal sinuses were reviewed. Symptoms included rhinorrhea, nasal obstruction, headache, facial pain and foul smell from the nose. At operation, these lesions appeared yellowish, brownish, grey or black in colour, and contained dirty or muddy material. Microscopic examination of the tissue removed showed an Aspergillus ball with chronic inflammation but without invasion of the nasal or sinus mucosa in 6 cases, and tissue invasion with necrosis and inflammation in 7. The structures involved, in order of frequency, were: maxillary sinus, nasal cavity, ethmoid sinus, orbit and cavernous sinus. The orbit was involved in 2 cases, therefore categorized as invasive; the other 11 cases were non-invasive as judged by CT. Calcification was seen in the lesions of 9 cases. In most cases the adjacent bony structures showed areas of erosion and sclerosis. Aspergillosis should be suspected in the presence of a mass in the paranasal sinuses or nasal cavity with calcification within it, which may not appear solid or dense and is separate from the walls of the sinus. PMID- 1436465 TI - Ascending pharyngeal artery-internal jugular vein fistula complicating radical neck dissection. AB - Arteriovenous fistulae of the ascending pharyngeal artery (AP) and internal jugular vein (IJ) are rare. Only two spontaneous AP-IJ fistulae have been described previously, both of which presented with pulsatile tinnitus. A unique case of an AP-IJ fistula developing after radical neck dissection is described in which the clinical presentation was identical to that of a carotid-cavernous fistula. PMID- 1436466 TI - Giant cell tumour of the skull base: MRI appearances. Case report. PMID- 1436467 TI - Chronic post-traumatic erosion of the skull base. AB - Delayed post-traumatic erosion of the skull base is reported in three patients who presented as adults with cerebrospinal fluid fistulae and a history of recurrent meningitis. These skull defects were associated with herniation of the subarachnoid space into the diploe of the skull base, the paranasal sinuses and the orbit. This rare complication of head injury is assumed to have occurred as the result of a dural tear at the time of trauma. Its site probably determines whether a resulting meningocele widens the intradiploic space or broaches the cranial floor. PMID- 1436468 TI - Double traumatic caroticocavernous fistula and its treatment by detachable balloons. PMID- 1436469 TI - Formation of an olfactory glomerulus: morphological aspects of development and organization. AB - We have studied the development of olfactory nerves in the rat from their first contact with the telencephalic vesicle until the formation of glomerular structures in the olfactory bulb at early postnatal period. The study is based on serial semithin and ultrathin sections of material prepared for electron microscopy and antibodies to label radial glial cells, glial fibrillary acidic protein and Rat-401. Beginning on embryonic day 12, developing olfactory axons from the olfactory placode are accompanied by migratory cells, also derived from the olfactory placode, that reach the prospective olfactory bulb by embryonic day 13. The mass of migratory cells accumulate superficial to the telencephalic vesicle. The cells increase in number by mitotic divisions. The majority of these cells represent precursor elements that will later develop into the ensheathing cells of the olfactory nerves and olfactory nerve layer of the adult. Some migratory cells penetrate into the prospective olfactory bulb early during development. The first synaptic contacts of olfactory axons with dendritic processes in the olfactory bulb were observed at embryonic day 18. Glomerular formation is initiated by penetration of cells from the migratory mass into the prospective glomerular layer by embryonic day 20 to postnatal day 0. These cells form walls surrounding zones of high synaptic density forming protoglomeruli. Postnatally, the peripheral processes of radial glial cells branch profusely delimiting glomerular formations and transform into periglomerular astrocytes. Rat-401 stains radial glial cells from embryonic day 14. Immunoreactivity becomes restricted to the olfactory glomeruli during the first postnatal weeks and it virtually disappears by the end of the first postnatal month. We conclude that the early penetration of cells from the migratory mass into the prospective olfactory bulb, observed immediately after the first synaptic contacts were established, initiates the formation of olfactory glomeruli which becomes completed by the transformation of radial glial cells into periglomerular astrocytes. PMID- 1436470 TI - Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson's disease and progressive supranuclear palsy: a quantitative autoradiographic study using [3H]mazindol. AB - It has been suggested that not only mesostriatal but also mesolimbic pathways are involved in the degeneration of dopaminergic neurons in Parkinson's disease. Using quantitative ligand autoradiography we have investigated dopamine transporter sites in basal ganglia of patients affected by Huntington's chorea, Parkinson's disease and progressive supranuclear palsy. [3H]Mazindol, a ligand for catecholamine uptake, was used in the presence of desipramine to block the binding to norepinephrine uptake sites. Schizophrenic cases were entered in the study to take into account the effects of neuroleptics, commonly administered also to Huntington's disease patients, on dopamine uptake sites. In control cases high densities of [3H]mazindol binding sites were found in the caudate nucleus, putamen and nucleus accumbens, whereas very low densities were present in substantia nigra and ventral tegmental area. In Huntington's chorea the density of [3H]mazindol binding sites was slightly decreased in the caudate nucleus, an area severely affected by the neurodegenerative process. In schizophrenic patients the density of dopamine uptake sites in the basal ganglia was slightly reduced, mainly in the middle third of putamen. Both Parkinson's disease and progressive supranuclear palsy populations were characterized by a marked loss of [3H]mazindol binding sites in the neostriatum (about 75%) and in the nucleus accumbens (about 65%). These results suggest that in Parkinson's disease and progressive supranuclear palsy severe decreases of dopamine uptake sites occur not only in the mesostriatal pathway but also in the mesolimbic tract. PMID- 1436471 TI - Mosaic distribution of phosphate-activated glutaminase-like immunoreactivity in the rat striatum. AB - The dorsal and ventral striatum of mammals has been known to be organized in a mosaic manner, referred to as "patches" and "matrix" of the caudatoputamen. The present study was primarily attempted in order to reveal the relationship of glutamatergic neuronal components to the mosaic organization in the rat striatum by using a monoclonal antibody to phosphate-activated glutaminase, a major synthetic enzyme of transmitter glutamate. Antibodies against glutamate decarboxylase and choline acetyltransferase were also used as the markers for GABAergic and cholinergic neuronal components, respectively. Glutaminase immunoreactivity was seen in a number of large- and a few medium-sized neurons in the caudatoputamen, nucleus accumbens and olfactory tubercle. The large neurons with glutaminase immunoreactivity were observed in the neuropil of the caudatoputamen and nucleus accumbens; glutaminase immunoreactivity was particularly marked in the neuropil of island-like patchy areas although it was seen throughout the neuropil of the nuclei. In the caudatoputamen, island-like areas with marked glutaminase immunoreactivity exhibited less marked choline acetyltransferase immunoreactivity than the surrounding background region, and were thus considered to correspond to the patches. The mosaic distribution of glutamate decarboxylase immunoreactivity in the caudatoputamen seemed identical with that of glutaminase immunoreactivity. However, in the nucleus accumbens, the mosaic pattern of neuropil labeling for glutaminase was neither consistent with that for glutamate decarboxylase nor that for choline acetyltransferase, suggesting the presence of non-GABAergic glutaminase-containing nerve terminals in the nucleus. In an attempt to clarify the origin of neuropil labeling for glutaminase in the striatum, lesions were made in the regions sending projection fibers to the caudatoputamen and nucleus accumbens. After placing lesions in the cerebral cortex, glutaminase immunoreactivity was decreased in neuropil of the caudatoputamen, but the mosaic pattern remained. Lesions which were placed in the intralaminar thalamic nuclei, amygdaloid body, globus pallidus or substantia nigra produced no substantial change in glutaminase immunoreactivity in the caudatoputamen and nucleus accumbens. After injection of kainic acid into the caudatoputamen or nucleus accumbens, glutaminase immunoreactivity in the neuropil of the affected regions was decreased to lose the mosaic pattern, indicating that neuronal components with glutaminase immunoreactivity in the neuropil of the patches were mainly of intrinsic origin. In summary, possible axon terminals containing glutaminase were observed with mosaic patterns in the caudatoputamen and nucleus accumbens, in which large cholinergic and medium-sized non cholinergic neurons were immunoreactive for glutaminase. In the caudatoputamen, glutaminase immunoreactivity in neuropil was more marked in the patches than in the matrix.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1436472 TI - The prolonged presence of glia-derived nexin, an endogenous protease inhibitor, in the hippocampus after ischemia-induced delayed neuronal death. AB - The presence of glia-derived nexin and glia fibrillary acidic protein (GFAP) was investigated in the hippocampus of Mongolian gerbils (Meriones unguiculatus) after transient forebrain ischemia. Bilateral clamping of the common carotid arteries for 7 min resulted in selective degeneration of CA1 pyramidal cells after a delay of three to four days, the so-called delayed neuronal death. Immunoreactivity for glia-derived nexin was found in astrocytes of all CA1 layers and was detectable until day 90 (the longest survival time studied). Astroglial reactivity was demonstrated in parallel by staining for GFAP. The co-localization of glia-derived nexin and GFAP was confirmed by double immunocytochemistry. Ultrastructural studies showed the exclusive presence of glia-derived nexin in astrocytes, in the vicinity of degenerating and preserved neuronal structures. Perivascular glia was intensely stained, but endothelial cells were devoid of immunoreactivity. Glia-derived nexin is a potent protease inhibitor with in vitro neurite-promoting activity. During adulthood, it is mainly present in the olfactory system, where receptor neurons are constantly being replaced. The ability of astrocytes to renew the expression of glia-derived nexin after selective delayed neuronal death and the prolonged presence of the protease inhibitor in a zone where degeneration occurs in the immediate neighborhood of preserved neuronal elements indicate that glia-derived nexin may play a role in structural rearrangements of the central nervous system. PMID- 1436473 TI - A monoclonal antibody to the interleukin-2 receptor enhances the survival of neural allografts: a time-course study. AB - A time-course study of the survival and immunological characteristics of rat neural allografts was undertaken in animals treated with a murine monoclonal antibody to the alpha-chain (p55) of the rat interleukin-2 receptor. This antibody, NDS 63, was administered for ten days following grafting beginning on the day of operation. Inbred rat strains differing at both major and minor histocompatibility loci were selected as donor and host. Furthermore, the recipient strain displayed a high responder major histocompatibility complex haplotype. All grafts were placed in the lateral ventricle. Comparison was drawn between NDS 63-treated recipients and two groups of controls; an untreated group and a second group treated with the monoclonal antibody NDS 66, directed at a second epitope on the alpha-chain of the interleukin-2 receptor, which has been shown to be ineffective in competing with interleukin-2 for binding. Immunocytochemical analysis of the transplants was performed at several time points up to 150 days following grafting. Grafts of NDS 63-treated recipients exhibited 100% survival with minimal induction of major histocompatibility complex antigens (both class I and class II) and negligible leukocyte infiltration at all time-points studied. In contrast grafts from both groups of controls showed evidence of a chronic immune response with most grafts undergoing rejection as shown by markedly elevated major histocompatibility complex antigen expression accompanied by specific immune cell infiltration. This was a protracted process with several grafts undergoing complete rejection by 60 days and a majority, but not all, by 150 days after transplantation. It is concluded that NDS 63, a monoclonal antibody to the interleukin-2 receptor, may diminish the immune response to transplanted allogeneic neural tissue and thereby enhance its prospects for long-term survival. PMID- 1436474 TI - Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat: an immunohistochemical study. AB - In the nervous system, the neural cell adhesion molecule changes at the cell surface during development, from a form highly enriched in polysialic residues to several isoforms containing much less sialic acid, and is thought to participate in the structuring of neuronal groups and in the establishment of neuronal connections. Recent observations have indicated, however, that it may not be restricted to developing tissues since it is still present in certain adult neuronal centres which can undergo morphological reorganization. In this study, therefore, we examined systematically the distribution of polysialylated neural cell adhesion molecule immunoreactivity throughout the central nervous system of adult male and female rats, using light microscopic immunocytochemistry and immunoblot analysis with an antibody that specifically recognizes the polysialic residues of the molecule. Concomitantly, we compared this immunoreactivity to that due to all isoforms of the neural cell adhesion molecule, detected with a polyclonal serum raised against the NH2-terminal of the protein. Immunoreactivity due to the polysialylated isoform was consistently visualized in several discrete areas of the adult brain and spinal cord. An intercellular punctate immunolabelling characterized the staining in certain hypothalamic and thalamic nuclei, superficial laminae of the dorsal horn of the spinal cord, ventral portion of the dentate gyrus of the hippocampus, lateral geniculate, parabrachial and habenular nuclei, bed nucleus of the stria terminalis, mesencephalic central gray and olfactory bulb. In other areas, such as the piriform cortex, dorsal aspect of the dentate gyrus and fimbria and lamina X of the spinal cord, isolated neuronal-like cells were either completely filled with immunolabel or showed a surface reaction on their cell bodies and processes. Highly immunoreactive isolated glial-like cells were also noted within the ependymal layer of the central canal and lateral ventricles and at times in the peripheral white matter of the spinal cord. In contrast to this discrete localization, staining due to all isoforms of the neural cell adhesion molecule was widespread and diffuse throughout the brain and spinal cord. The expression of the polysialylated isoform in the supraoptic nucleus and hippocampus was confirmed by immunoblot analysis; it occurred together with weakly sialylated isoforms. No obvious differences were detected in the amount or distribution of immunoreactivity due to the polysialylated isoform in relation to the sex or age of the animals (between three and 12 months of age). Our study thus demonstrates that well defined areas of the central nervous system of the adult rat continue to express the polysialylated isoform of the neural cell adhesion molecule.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1436475 TI - Cell-cell contact modulates expression of cell adhesion molecule L1 in PC12 cells. AB - The effect of cell contact on the expression of cell adhesion molecule L1 was investigated. The rat pheochromocytoma cell line PC12 cells were cultured at various densities in the presence or absence of the nerve growth factor. The addition of the nerve growth factor promoted the expression of L1. The expression of L1 was higher when the cells were cultured at high density than when done at low density both in the presence or absence of the nerve growth factor. Immunohistochemical staining of L1 showed that the expression of L1 was higher in the cells contacting each other. These results show that cell interaction affects the expression of cell adhesion molecule L1 in the PC12 cells. PMID- 1436476 TI - Effects of nerve growth factor on the biosynthesis of chromogranin A and B, secretogranin II and carboxypeptidase H in rat PC12 cells. AB - We investigated the biosynthesis of various constituents (chromogranins A and B, secretogranin II, carboxypeptidase H and synaptin/synaptophysin) of large dense core and small vesicles in PC12 cells. These cells were treated for up to 18 days with nerve growth factor. Peptide levels were determined by quantitative immunoblotting, their mRNAs by Northern blotting. Nerve growth factor treatment changed the levels of the various peptides investigated and their mRNAs in three patterns. Peptide and mRNA levels for chromogranin A and chromogranin B were increased on day 1 and then declined. Synaptin/synaptophysin levels slightly decreased from day 1 onwards. On the other hand secretogranin II increased steadily up to 217% for peptide levels and 257% for mRNA levels. For carboxypeptidase H for which only the mRNA could be determined an analogous behaviour was seen. Its mRNA after 14 days of nerve growth factor treatment was 459% of controls. These results establish that the biosynthesis of the secretory proteins chromogranin A, chromogranin B and secretogranin II is regulated differentially during nerve growth factor treatment. We suggest that neuronal differentiation is accompanied by an increased biosynthesis of secretogranin II. For carboxypeptidase H, the marked increase in mRNA levels after nerve growth factor treatment is the first example that the biosynthesis of this peptide is significantly up-regulated. Synaptin/synaptophysin biosynthesis is not increased although this peptide is a major constituent of small vesicles which increase in number during nerve growth factor treatment. PMID- 1436477 TI - Differential cerebrovascular and metabolic responses in specific neural systems elicited from the centromedian-parafascicular complex. AB - The effect of electrical stimulation of the centromedian-parafascicular complex on local cerebral blood flow and local cerebral glucose utilization was investigated in anesthetized, paralysed and ventilated rats. Local cerebral blood flow and local cerebral glucose utilization were measured in separate groups of animals using the autoradiographic (14C)iodoantipyrine and (14C)2-deoxyglucose methods, respectively. Because of the well-established centromedian parafascicular complex neuroanatomical connections, three functional neuronal systems were analysed and compared: the extrapyramidal motor system the limbic system and the reticular formation, also known as the ascending activating system. Cortical regions not included in the limbic system were considered separately. The validity of comparisons between changes in local cerebral blood flow and local cerebral glucose utilization across the brain was verified by assessing the reactivity and stability of the cortical blood flow during long term centromedian-parafascicular complex stimulation. Centromedian-parafascicular complex stimulation elicited a marked but heterogeneous increase in local cerebral blood flow in 50 of the 52 cerebral structures measured. The most pronounced increases were seen in the lateral habenular nucleus (331 +/- 30% of control), the zona incerta (400 +/- 55%), the mesencephalic reticular formation (415 +/- 122%) and the parietal cortex (211 +/- 35%). In contrast, local cerebral glucose utilization remained statistically unchanged (P greater than 0.05) in 28 of these 50 individual brain regions during centromedian-parafascicular complex stimulation. The most pronounced increases in local cerebral glucose utilization were seen in the zona incerta (123 +/- 28%) and the mesencephalic reticular formation (193 +/- 26%). Local cerebral blood flow and local cerebral glucose utilization were linearly related in unstimulated controls, considering either all brain regions taken as a whole or the three systems separately. The significant increase in the slopes of the regression line between local cerebral blood flow and local cerebral glucose utilization for the reticular formation and the limbic system during centromedian-parafascicular complex stimulation indicates, however, that the coupling mechanisms for these systems, but not for the extrapyramidal motor system, were reset. The local cerebral blood flow to local cerebral glucose utilization ratio was heterogeneous in controls and differentially increased during centromedian-parafascicular complex stimulation, being markedly pronounced in the parietal cortex and in the reticular formation. We conclude that these results, for the first time, provide evidence that, the functionally well-defined neural networks may have different mechanisms whereby changes in vascular and metabolic demands are regulated. PMID- 1436478 TI - A model for the generation of movements requiring endpoint precision. AB - A model is proposed in which movement accuracy is regulated by means of corrective actions taken at discrete intervals throughout the course of a movement. A movement, as represented by its tangential velocity profile, cna be decomposed into a series of one or more submovements. Each submovement consists of a prototype velocity profile which can be scaled in magnitude and duration. For planar two-joint movements, we demonstrate that these submovements can be mathematically represented either in terms of velocity profiles or in terms of the underlying joint torque profiles. In either case, the submovements superimpose linearly to produce the composite movement. The model provides a very good fit to tangential velocity profiles recorded from human subjects during three-dimensional arm movements with constraints on accuracy and speed. The model assumes that when a submovement is present, its onset is associated with a change in the direction of the hand path and/or a zero crossing or inflection in at least one of the components of the velocity vector. The model is consistent with a strategy in which precision is achieved by periodic discrete actions which redirect the moving arm in order to bring the hand closer to the target. Since submovements were also observed in slow movements where accuracy constraints had been relaxed, we hypothesize that the strategy of superimposing a series of submovements to make one composite movement may be a general one. We suggest that it would be particularly appropriate for the process of learning a new motor skill. PMID- 1436479 TI - Monoamine oxidase-B in motor cortex: changes in amyotrophic lateral sclerosis. AB - The occurrence of monoamine oxidase-B in cerebral cortex and white matter in brains from three patients with the diagnosis of amyotrophic lateral sclerosis and three controls was quantified by means of an autoradiographical method. [3H]L Deprenyl, an irreversible and selective monoamine oxidase-B inhibitor, was used as ligand and the autoradiographs were analysed by computer-assisted densitometry. In both amyotrophic lateral sclerosis and control cerebral cortex, lamina I showed the highest, laminae II and III intermediate, laminae IV, V and VI the lowest [3H]L-deprenyl binding. White matter showed about one-third of the binding in the cortex. Amyotrophic lateral sclerosis cases showed significantly higher binding of [3H]L-deprenyl in all the cortex laminae of the pre- and postcentral gyri. There was no difference in the binding between the amyotrophic lateral sclerosis cases and the controls in area 7 of the occipital cortex, an area which is relatively spared in amyotrophic lateral sclerosis. PMID- 1436480 TI - Transient lesion-induced increase of basic fibroblast growth factor and its receptor in layer VIb (subplate cells) of the adult rat cerebral cortex. AB - Basic fibroblast growth factor is a potent trophic factor with a wide spectrum of activity at various stages of neuronal development. In our studies on the effects of select lesions on the expression of growth factors, we observed that neurons of layer VIb of the rat cerebral cortex developed immunoreactivity for basic fibroblast growth factor and its receptor following injury. Recent evidence indicates that layer VIb of the rat cerebral cortex contains the subplate cell population, a group of neurons shown to participate in the development of the cerebral cortex. In this article, we examined the nature and time-course of the response to injury of the expression of basic fibroblast growth factor and its receptor in these cells. We used an anti-basic fibroblast growth factor monoclonal antibody that recognizes the active form of basic fibroblast growth factor, and a polyclonal antibody that recognizes the extracellular domain of the basic fibroblast growth factor receptor. The induction of basic fibroblast growth factor and its receptor in layer VIb cells occurred after entorhinal cortex lesion, fimbria-formix transection or aspiration of small segment of the frontoparietal cortex. The lesion-induced effect was transient, appearing by postlesion day 2 and having disappeared by postlesion day 7. These findings suggest that endogenous basic fibroblast growth factor may have a neuroprotective role on layer VIb neurons after trauma and/or may participate in cortical plasticity during adulthood. PMID- 1436481 TI - Glial fibrillary acidic protein immunoreactivity following cortical devascularizing lesion. AB - Disruption of a restricted area of the pia-arachnoid compromises vascular irrigation of the underlying cortex, leading to infarction of the tissue. This study was undertaken to examine the effects of such brain injury on glial cells. Adult male Wistar rats were processed for glial fibrillary acidic protein immunoreactivity at 1, 4, 7, 15 and 30 days after undergoing cortical devascularization. One day post-lesion, glial fibrillary acidic protein-positive cells were observed only at the lesion site. Glial fibrillary acidic protein positive cells were present in the ipsilateral remaining cortex, distant from the wound, between days 4 and 15, and were also evident in the thalamus beginning 4 days post-lesion. These diverse temporal patterns of GFAP immunoreactivity in different brain structures suggest that various mechanisms can mediate increased GFAP immunostaining following injury. PMID- 1436482 TI - Abnormal Ca2+ homeostasis before cell death revealed by whole cell recording of ischemic CA1 hippocampal neurons. AB - Slices were made from the hippocampus of gerbils following transient ischemia achieved by clamping the carotid arteries for 5 min, and changes in the electrophysiology of CA1 pyramidal neurons were studied by whole cell patch-clamp recording as well as conventional intracellular recording. The great majority of CA1 neurons in slices made 2.5-3 days after ischemia showed reduced resting potentials and were easily depolarized by prolonged low-frequency stimulation or by tetanic stimulation of the Schaffer collateral/commissural input. This stimulus-induced depolarization was accelerated by intracellular injection of D myo-inositol 1,4,5-triphosphate, which depolarized membrane potentials towards 0 mV without synaptic input stimulation. Intracellular application of BAPTA, a Ca2+ chelator, effectively blocked the stimulus-induced depolarization. When recording from ischemic neurons with patch pipettes containing both D-myo-inositol 1,4,5 triphosphate and BAPTA, excitatory postsynaptic currents were transiently potentiated by stimulation, but the membrane potential did not show stimulus induced depolarization and remained steady for long periods. These results lend support to the view that the intracellular Ca2+ regulation system is severely disturbed following ischemia, and that input fiber stimulation leads to abnormal Ca2+ accumulation in ischemic neurons resulted in neuronal death. The reduction of free Ca2+ inside the ischemic neuron by BAPTA apparently saves neurons which are otherwise destined to delayed neuronal death. PMID- 1436483 TI - Postsynaptic then presynaptic protein kinase C activity may be necessary for long term potentiation. AB - Protein kinase C inhibitor was injected intracellularly by iontophoresis into CA1 somata either before or after long-term potentiation in the hippocampal slice preparation. Two different protein kinase C inhibitors, polymyxin B (PMXB) or 1 (5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), injected 10 min before long term potentiation induction caused potentiated responses to return to baseline 15 35 min after induction without significantly affecting the initial magnitude of potentiation. There was no effect on long-term potentiation persistence when H-7 or PMXB was injected intracellularly 5 min after long-term potentiation induction. In contrast, focal extracellular micro-pressure ejection of protein kinase C inhibitor in the stratum radiatum, 15 or 30 min, but not 60 min after long-term potentiation induction caused decay of long-term potentiation to baseline. This is probably a presynaptic action since intracellular inhibitors injected postsynaptically were ineffective 5 min after long-term potentiation induction. Focal application to stratum pyramidale produced a weaker decay than to stratum radiatum suggesting a Schaffer collateral presynaptic terminal site of action. We propose that activation of postsynaptic protein kinase C activity is necessary for long-term potentiation persistence but this activity persists for less than 5 min after induction. Presynaptic protein kinase C activity is also necessary for persistence and is time-limited to less than 60 min. It is attractive to think that these two events are sequentially activated and employ different protein kinase C subtypes differentially localized to presynaptic or postsynaptic elements. PMID- 1436484 TI - The low molecular weight guanosine triphosphate-binding protein Rab6p associates with distinct post-Golgi vesicles in Torpedo marmorata electrocytes. AB - The Rab genes have recently been cloned and sequenced in mammals, and their products represent good candidates for low molecular weight guanosine triphosphate-binding proteins involved in the regulation of intracellular transport of vesicles in higher eukaryotes. Remarkably, each of the Rab proteins appears to be associated with a distinct step of either the exocytic or endocytic pathway. In particular, Rab6p has been localized to the outermost Golgi cisternae in normal rat kidney cells, where its function remains unclear. In this work, we have carried out a series of immunocytochemical analyses of the subcellular distribution of Rab6p in a polarized cell, the electrocyte of Torpedo marmorata, to elucidate the molecular mechanisms involved in the sorting and targeting of synaptic proteins. We report that, aside from its Golgi localization, the bulk of Rab6p associates with clusters of post-Golgi vesicles, primarily those located at the cytoplasmic face of the innervated membrane of the electrocyte. Consequently, Rab6p presents a polarized distribution in this cell. Furthermore, we show that this distribution is dependent upon the integrity of the microtubule network of the electrocyte. These data are coherent with the notion that Rab6p is involved in the regulation of membrane traffic from the trans-Golgi network to the innervated plasma membrane, delivering, by way of a microtubule-based organelle transport mechanism, synaptic proteins to their appropriate locations. PMID- 1436485 TI - Inhibitory effects of ventral tegmental area stimulation on the activity of prefrontal cortical neurons: evidence for the involvement of both dopaminergic and GABAergic components. AB - The medial prefrontal cortex of the rat receives dopamine and non-dopaminergic projections from the ventral tegmental area. Both electrical stimulation of the ventral tegmental area and local application of dopamine induce an inhibition of the spontaneous activity of most prefrontal cortical neurons, including efferent neurons. In the present study, the techniques of extracellular recording and microiontophoresis were used in anesthetized rats in order to determine whether these dopamine- and ventral tegmental area-induced inhibitory responses involve GABAergic components. Prefrontal cortex output neurons were identified by antidromic activation from subcortical structures. The inhibitory responses evoked by the local application of dopamine were blocked by the iontophoretic application of the D2 antagonist sulpiride, and the GABAA antagonist bicuculline in 89 and 57% of the cases, respectively. In addition, sulpiride and bicuculline abolished the inhibition induced by ventral tegmental area stimulation in 54 and 51% of the prefrontal cortical cells tested, respectively. The implication of a non-dopaminergic mesocortical system in the ventral tegmental area-induced inhibition was further analysed using rats pre-treated with alpha methylparatyrosine to deplete dopamine stores. The proportion of prefrontal cortical cells inhibited by ventral tegmental area stimulation was markedly reduced (39%) in alpha-methylparatyrosine-treated rats, when compared to controls (86%). Remaining ventral tegmental area-induced inhibition was no longer affected by sulpiride, but in all cases blocked by the local microiontophoretic application of bicuculline. The present results suggest that: (1) the dopamine induced inhibition of prefrontal cortex neurons could involve cortical GABAergic interneurones; (2) the non-dopaminergic mesocortical system exerts also an inhibitory influence on prefrontal cortical cells and appears to be GABAergic. PMID- 1436486 TI - Pharmacological evidence for common mechanisms underlying the effects of neurotensin and neuroleptics on in vivo dopamine efflux in the rat nucleus accumbens. AB - The effects of the neuropeptide neurotensin and the typical neuroleptic haloperidol on dopamine efflux were compared in the posteromedial nucleus accumbens of the chloral hydrate-anesthetized rat using in vivo chronoamperometry. Both neurotensin and haloperidol administration elicited an immediate increase in dopamine efflux in the nucleus accumbens. Gamma hydroxybutyric acid lactone, an agent known to block impulse flow in dopamine neurons, either prevented when given before neurotensin or reversed neurotensin induced increases in accumbens dopamine efflux. Haloperidol-induced increases in accumbens dopamine efflux were similarly affected by gamma-hydroxybutyric acid lactone. The dopamine receptor agonist apomorphine reversed neurotensin- and haloperidol-induced increases in dopamine efflux. Amphetamine, administered during the peak dopamine stimulatory effects induced by neurotensin or haloperidol, resulted in increases above baseline which were significantly greater than the effects of amphetamine alone. These combined drug treatment effects on baseline dopamine efflux were additive, indicating that the effects of amphetamine were not potentiated by neurotensin or haloperidol pretreatments. These in vivo results suggest that neurotensin and haloperidol may augment dopamine efflux in the nucleus accumbens via common mechanisms of action which may involve activation of mesotelencephalic dopamine neuronal firing. The inability of neurotensin to block amphetamine-induced efflux in the nucleus accumbens further suggests that neurotensin blockade of amphetamine-elicited locomotor activity is mediated by an action of neurotensin postsynaptic to dopamine nerve terminals in the nucleus accumbens. PMID- 1436487 TI - Changes of rat striatal neuronal membrane morphology and steroid content during the estrous cycle. AB - It is well documented that sex steroids affect striatal dopamine systems. However, the mechanism(s) of these hormonal effects in the striatum is still not well understood. We now report that gonadal steroid hormones during the estrous cycle affect the morphology and steroid hormone content of the rat striatum. Rats displaying at least two consecutive estrous cycles were included in this study as well as a group of female rats ovariectomized two weeks before being killed. The striatum was dissected from one half of each brain and used for morphological studies. From the other half of each brain, the striatum was dissected and steroid hormone concentrations in striatum and the remainder of the brain were determined. Tissues and serum concentrations of 17 beta-estradiol, progesterone and prolactin were measured by specific radioimmunoassays. Serum 17 beta estradiol and prolactin concentrations peaked in proestrus, while progesterone was high in diestrus and proestrus. 17 beta-Estradiol levels were higher in the striatum than in the rest of the brain; both were also shown to fluctuate during the estrous cycle and with a pattern similar to that observed in serum. Progesterone serum levels showed a similar pattern of changes during the estrous cycle to progesterone concentrations in the striatum and the rest of the brain. The ultrastructure of the striatal dendritic membranes was studied by freeze fracture. A significant difference in the content of intramembranous particles in dendritic shafts, which are mainly contacted by dopaminergic synapses, was found during the estrous cycle. The numerical density of large (greater than 10 nm) intramembranous particles was increased in diestrus I and II and in the afternoon of proestrus compared to estrus, the morning of proestrus and ovariectomized rats. In contrast, the numerical density of small (less than 10 nm) intramembranous particles was decreased in cycling animals compared to ovariectomized rats and fell in the afternoon of proestrus and then progressively increased in the following days to peak in the morning of proestrus. A negative correlation between steroid concentrations and small intramembranous particle density was observed, while the correlation was positive for large particles. No changes were observed in the membranes of dendritic spines, the main postsynaptic target for cortical afferents. In summary, this is the first report that concentrations of 17 beta-estradiol and progesterone in the striatum fluctuate during the estrous cycle. This is associated with estrous cycle-dependent changes of intramembranous particle density of striatal dendritic membranes. Our data therefore indicate that the striatum is a brain region hormonally modulated under physiological conditions. PMID- 1436488 TI - Diverse actions of 5-hydroxytryptamine on frog spinal dorsal horn neurons in vitro. AB - The effects of 5-hydroxytryptamine on the membrane potential and input resistance of 86 dorsal horn neurons were studied using intracellular recordings in isolated, hemisected spinal cords of adult frogs (Rana pipiens). Bath application of serotonin (5-100 microM) caused membrane depolarizations in 58 (67%) neurons, hyperpolarizations in 12 (14%) cells, biphasic responses in nine (11%) neurons, and no detectable change in seven (8%) cells. In some neurons depolarized by serotonin, the amine's responses could be mimicked by the selective 5-HT2 agonist (+/-)-1(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride and the 5-HT1C/2 agonist alpha-methyl-5-hydroxytryptamine, and blocked by the 5-HT1C/2 antagonists ketanserin and mianserin. In other neurons depolarized by serotonin, the 5-HT3 agonist 2-methyl-5-hydroxytryptamine mimicked, and the 5-HT3 antagonist, 3 tropanyl-3,5-dichlorobenzoate, blocked the serotonin-induced responses. Depolarizing responses due to activation of 5-HT1C/2 receptors were generally accompanied by increases in the membrane input resistance, whereas depolarizations mediated by 5-HT3 receptors were associated with a decreased membrane input resistance. Superfusion with tetrodotoxin or low-Ca2+/high-Mg(2+) containing media abolished about half of the depolarizing responses. Hyperpolarizations caused by serotonin were associated with a decrease in membrane input resistance, and might have been due to activation of a potassium conductance. These responses persisted in bathing solutions containing tetrodotoxin or low-Ca2+/high-Mg2+. The 5-HT1A agonist 8-hydroxy-2-(di-N propylamine)tetralin hydrobromide mimicked, whereas the 5-HT1A antagonist spiroxatrine blocked, these hyperpolarizing responses. Other antagonists selective for 5-HT1C/2 or 5-HT3 receptors were without effect. Serotonin-produced biphasic responses consisted of either an initial depolarization followed by a hyperpolarization or the reverse. The selective 5-HT2 agonist (+/-)-1(2,5 dimethyoxy-4-iodophenyl)-2-aminopropane hydrochloride could only mimic the depolarizations, whereas the 5-HT1A agonist 8-hydroxy-2-(di-N propylamine)tetralin hydrobromide produced only the hyperpolarizations. Spiroxatrine, a 5-HT1A antagonist, blocked only the hyperpolarizations without affecting the depolarizations, and methysergide, a non-specific 5-HT receptor antagonist, depressed both the depolarizations and hyperpolarizations. Serotonin also appeared to affect spinal dorsal horn neurons indirectly because it produced excitatory postsynaptic potentials, inhibitory postsynaptic potentials, and a mixture of both.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1436489 TI - Choline blockage of currents through Ca(2+)-activated K+ channels in bovine chromaffin cells. AB - The action of choline on "maxi" Ca(2+)-activated K+ channels was studied in excised patches of bovine chromaffin cell membranes. Choline (20-70 mM) applied to the internal surface of the membrane reduced the single channel current amplitudes, which can be explained by a fast channel block. The block is concentration- and voltage-dependent and is rapidly and completely reversed upon washout. The block becomes progressively greater with depolarization. The estimates of blocking parameters vary from channel to channel but appear to fall in two groups. A larger group (two-thirds of cases) with moderate affinity [KD(0) = 88.5 mM] and low voltage dependence (delta = 0.26) and a smaller group (one third of cases) with very low affinity (KD = 306 mM) and moderate voltage dependence (delta = 0.59). The open state probability appears not to be affected at any choline concentration (up to 70 mM) or membrane potential (from -20 to +60 mV) studied, suggesting that choline does not affect the channel gating kinetics. Since the affinity of the choline block is low to moderate, the intracellular choline is not expected to alter the current flow through "maxi" Ca(2+)-activated K+ channels unless the choline concentration close to the protoplasmic membrane is much higher than the mean cellular concentration. PMID- 1436490 TI - Termination pattern and fine structural characteristics of GABA- and [Met]enkephalin-containing nerve fibers and synapses in the superior cervical ganglion of adult rat. AB - Morphological features of nerve fibers and synapses containing GABA and [Met]enkephalin were studied at the light and electron microscopic levels in the superior cervical ganglia of rats by pre- and postembedding immunohistochemistry. Both GABA and [Met]enkephalin immunoreactivities were found in varicose nerve fibers, forming diffuse networks which were denser in the rostral than in the caudal part of each ganglion. For both antigens rich and basket-like innervation was observed around some of the principal neurons. The GABA-immunoreactive fibers were evenly stained, while in case of [Met]enkephalin-positive nerve fibers the varicosities showed intensive immunopositivity only. Postembedding immunochemistry revealed that both inhibitory substances were located in axon varicosities which established asymmetric synapses of Gray I type. Fine structural investigation revealed that GABA-like immunoreactivity was confined in the nerve endings to the clear synaptic vesicles of 40 nm diameter, whereas the immunogold particles, indicating the occurrence of [Met]enkephalin, were located over the large dense-cored vesicles of 120 nm diameter. The clear and dense-cored vesicles were, however, mixed in the nerve endings labeled by either neurotransmitter substance. Interestingly, the [Met]enkephalin-immunopositive axon terminals were found, consequently, in synaptic contacts with dendrites containing dense bodies in a row underlying the postsynaptic membrane thickening. Since nerve terminals with GABA-like immunoreactivity established synapses of Gray I type without such subjunctional bodies, one can reasonably assume that, in spite of similarities in termination pattern, there is no co-existence of GABA and enkephalin in the axons in the superior cervical ganglion. PMID- 1436491 TI - Ankle joint (artc. intertarsalis) receptors in the domestic fowl. AB - The physiological responses of joint capsule sensory receptors in the ankle joint of the chicken were studied by recording the electrical activity from single sensory afferent nerve fibres dissected from the parafibular nerve. All units included in this study were sensitive to mechanical stimulation of the joint capsule and were classified with respect to nerve conduction velocity, receptive field size and response threshold. Rapidly adapting mechanoreceptors formed 23% of the receptors present in the sample and responded to the mechanical probe by giving a single response or a short burst of activity at the onset of stimulation. The majority of units identified showed a slowly adapting response and on the basis of conduction velocity were divided into group IV (CV 2.5 m/s), group III (CV 2.5-20 m/s) and those units conducting over 20 m/s. Group IV units had single spot-like receptive fields and mechanical thresholds ranging from 0.6 to 60 g. Group III units could be divided into two groups based on receptive field size. One group had spot-like receptive fields 1-2 mm in diameter, whereas in the other group the receptive fields were larger (over 2 x 3 mm). The large receptive field units had significantly faster conduction velocities, lower mechanical thresholds and steeper stimulus-response curves than small receptive field units. In response to movement of the joint very few of the receptors, whether rapidly or slowly adapting, were found to be excited by moving the joint by hand in the middle of its physiological range. The physiological properties of these avian mechanoreceptive fine afferent units suggest that while some are activated by normal joint movement and non-noxious local mechanical stimulation of the joint capsule, others have nociceptive functions. The receptors present in the ankle joint were correlated with the anatomical structures found in the avian joints and their physiological properties compared and contrasted to the joint receptors found in mammals. PMID- 1436493 TI - Presence of calbindin and lack of parvalbumin in progesterone receptor-containing neurons of the monkey mediobasal hypothalamus. AB - All of the progesterone receptor-containing cells of the monkey hypothalamus are GABAergic. The aim of this study was to further characterize these GABAergic progesterone receptor-containing neurons based on their calbindin or parvalbumin content. These calcium-binding proteins are characteristic markers of different populations of GABAergic neurons in the central nervous system. Double immunolabeling for progesterone receptor and either calbindin or parvalbumin was performed on hypothalamic Vibratome sections of estrogen primed African green monkeys (Cercopithecus aethiops). Progesterone receptor-containing calbindin immunoreactive neurons were observed in the ventromedial and periventricular areas of the hypothalamus. Forty-one per cent of the progesterone receptor containing cells in this area were calbindin immunopositive. No double immunolabeled neurons could be detected in the infundibular (arcuate) nucleus. In tissue double-immunolabeled for progesterone receptor and parvalbumin, none of the progesterone receptor-containing neurons exhibited immunoreactivity for parvalbumin. Electron microscopic double-immunostaining for progesterone receptor and calbindin confirmed the light microscopic results. Furthermore, a large number of asymmetric synaptic contacts were observed on the calbindin immunoreactive neurons. These observations demonstrate that progesterone receptor containing cells in the monkey mediobasal hypothalamus consist of at least two different types of GABA neurons, and indicate that progesterone receptor containing calbindin cells may be postsynaptic targets of excitatory fibers. PMID- 1436492 TI - Cloning of human neurotensin/neuromedin N genomic sequences and expression in the ventral mesencephalon of schizophrenics and age/sex matched controls. AB - A human genomic clone encompassing exons 1-3 of the neurotensin/neuromedin N gene was identified using a canine neurotensin complementary DNA probe. Sequence comparisons revealed that the 120-amino acid portion of the precursor sequence encoded by exons 1-3 is 89% identical to previously determined cow and dog sequences and that the proximal 250 bp of 5' flanking sequences are strikingly conserved between rat and human. The 5' flanking sequence contains cis-regulatory sites required for the induction of neurotensin/neuromedin N gene expression in PC12 cells, including AP1 sites and two cyclic adenosine-5'-monophosphate response elements. Oligonucleotide probes based on the human sequence were used to examine the distribution of neurotensin/neuromedin N messenger RNA in the ventral mesencephalon of schizophrenics and age- and sex-matched controls. Neurotensin/neuromedin N messenger RNA was observed in ventral mesencephalic cells some of which also contained melanin pigment or tyrosine hydroxylase messenger RNA. Neurons expressing neurotensin/neuromedin N messenger RNA were observed in the ventral mesencephalon of both schizophrenic and non-schizophrenic humans. PMID- 1436494 TI - A comparison of the electrophysiological properties of morphologically identified cells in layers 5B and 6 of the rat neocortex. AB - In vitro studies performed in mammalian brain slices have shown that cortical neurons differ in their intrinsic membrane properties. In the rodent cortex these properties are related to a specific cell morphology and synaptic connectivity in some cells but not in others. Due to their small size, little is known about the intrinsic membrane properties of layer 6 cells, however, and it is not clear whether cell morphology is related to electrophysiological properties in this layer. We used a combination of intracellular recording and dye-filling to study the electrophysiological and morphological characteristics of layer 6 cells of the rat sensorimotor cortex in vitro and compared their properties to those of large layer 5B pyramidal cells. Our sample of 24 filled and anatomically reconstructed cells in layer 6 confirms previous Golgi studies that showed them to be a morphologically diverse group consisting of regularly and irregularly oriented pyramidal cells and spiny nonpyramidal cells. Regular layer 6 pyramidal cells differed with respect to the length of their apical dendrites and extent of their axonal arborizations, while irregularly oriented pyramidal cells consisted of sideways or inverted pyramidal cells of variable size and morphology. Spiny nonpyramidal cells included bi-tufted and multi-polar cell types that differed in size and extent of dendritic trees. Many layer 6 cells showed long horizontal axon collaterals in layer 6, and an oblique or vertical projection to layer 4. Stimulation with intracellular constant current pulses revealed that the morphological diversity was mirrored by a similar electrophysiological diversity. Most layer 6 cells were capable of firing trains of action potentials characterized by an initial doublet or triplet followed by a train of single spikes (phasic-tonic mode). The majority of layer 6 cells could fire in either a tonic (single spikes only) mode with low strength current input and a phasic tonic pattern with higher current strengths. A minority fired either always phasic-tonic or tonic-only spike trains. The size and sequence of spike afterpotentials during low-rate repetitive firing was highly variable in layer 6 cells suggesting that the relative importance of ionic currents responsible for spike repolarization and afterpotentials varied from cell to cell. Subthreshold responses showed prominent inward rectification, while hyperpolarizing "sag" was present in most cells tested. In comparison, large layer 5B pyramidal cells fired either phasic-tonic only or both phasic-tonic and tonic patterns. A minority of cells were capable of firing repetitive bursts, while the remainder fired repetitive single spikes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1436495 TI - Ketamine blocks cortical epileptic afterdischarges but not paired-pulse and frequency potentiation. AB - Cortical epileptiform afterdischarges (spike-and-wave rhythm) induced by low frequency stimulation of the sensorimotor cortex were dose-dependently shortened by ketamine (10, 20 and 40 mg/kg, i.p.). Myoclonic jerking during stimulation was unaffected by ketamine whereas the same motor pattern accompanying afterdischarges was markedly suppressed by this drug. Paired-pulse as well as frequency potentiation of the cortical interhemispheric (transcallosal) responses were not significantly altered by the 40 mg/kg dose of ketamine. The two simple potentiation phenomena studied probably did not play a role in initiation of cortical epileptic afterdischarges. PMID- 1436496 TI - Spontaneous and evoked activity of the caudate neurons to central and peripheral stimuli after brain lesions. AB - The involvement of the cerebral cortex, commissural fibers and thalamus on caudate-caudate relations was studied in locally anesthetized, paralysed and artificially ventilated cats. This type of experimental preparation was necessary since a complete suppression of spontaneous and evoked activity is produced by subanesthetic doses of general anesthesia. Two types of caudate action potentials were encountered on the basis of their waveform characteristics: biphasic and triphasic spikes, the former being the largest population (80%). These waveforms were independent of the microelectrode resistance and the distance to recorded neurons. However, their responses were very similar to both central and peripheral stimuli. Caudate stimulation depressed the spontaneous discharges of the majority of the responsive units recorded within the opposite nucleus, while striatal neurons were activated by stimulation of the contralateral cortex. Decortication, thalamic lesion (motor nuclei and massa intermedia) and section of the corpus callosum decrease the firing rates of caudate neurons with biphasic spikes, while the discharges of the neurons with triphasic action potentials remained unchanged. Bilateral ablation of the cerebral cortex decreased the responsiveness of striatal neurons to contralateral nucleus and sciatic nerve and reduced the number of spontaneously active cells per recording tract. Section of the commissural fibers also depressed the caudate responses to the contralateral nucleus, and to the opposite precruciate cortex, although thalamic lesion did not affect the responsiveness of caudate cells to both central and peripheral stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436497 TI - Peripheral vibration causes an adenosine-mediated postsynaptic inhibitory potential in dorsal horn neurons of the cat spinal cord. AB - We have previously reported a vibration-induced, adenosine-mediated inhibition of nociceptive dorsal horn neurons in the cat spinal cord. The present study was conducted to investigate the mechanisms of this inhibition. In vivo intracellular recording was obtained from dorsal horn neurons in the lower lumbar segments of the anaesthetized cat. Vibration (80-250 Hz for 2-3 s every 15-20 s) was applied to the glabrous skin of the toes of the hind foot using a feedback-controlled mechanical stimulator. In 32 of 43 neurons tested, vibration produced a pronounced hyperpolarization of the membrane potential. This hyperpolarization peaked at -10 mV and decayed throughout the period of the application of vibration. It was associated with a decrease in membrane resistance, had a reversal potential negative to the resting membrane potential and was Cl(-) independent, suggesting that it was due to an increase in a K+ conductance, properties typical of the response to adenosine. This inhibitory postsynaptic potential was unaffected by intravenous administration of bicuculline, strychnine and naloxone but was blocked by iontophoretic administration of 8 sulphophenyltheophylline, a P1-purinergic receptor antagonist. These results confirm our previous finding that vibration-induced inhibition of nociceptive dorsal horn neurons is mediated via the release of an endogenous purine compound and further suggests that this inhibition involves a postsynaptic inhibitory mechanism. PMID- 1436498 TI - Histamine modulates heat stress-induced changes in blood-brain barrier permeability, cerebral blood flow, brain oedema and serotonin levels: an experimental study in conscious young rats. AB - The possibility that endogenous histamine plays an important role in modulating the pathophysiology of heat stress was examined in young rats using a pharmacological approach. Subjection of young animals (six to seven weeks old) to heat stress at 38 degrees C for 4 h in a biological oxygen demand incubator (relative humidity 47-50%, wind velocity 20-25 cm/s) resulted in a profound increase in blood-brain barrier permeability to Evans Blue albumin (whole brain 375%) and [131I]sodium (whole brain 478%) along with a significant reduction in the cerebral blood flow (mean 34%). The water content of the whole brain was elevated by 4.5% (about 19% volume swelling) from the control. At this time period, the plasma and whole brain 5-hydroxytryptamine levels were elevated by 656% and 328%, respectively, from the control group. Pretreatment with cimetidine (a histamine H2 receptor antagonist) significantly thwarted the increases in the brain water content and the blood-brain barrier permeability. In cimetidine pretreated animals, the cerebral blood flow was significantly elevated and the plasma and brain 5-hydroxytryptamine (serotonin) levels were slightly but significantly reduced as compared with the untreated stressed group. However, prior treatment with mepyramine (a histamine H1 receptor antagonist) neither attenuated the changes in water content and the blood-brain barrier permeability nor altered the cerebral blood flow and 5-hydroxytryptamine levels. In fact, there was a significantly higher permeation of the tracers across the cerebral vessels in these drug-treated animals along with a greater accumulation of the brain water content as compared with the untreated stressed group. The cerebral blood flow and 5-hydroxytryptamine levels showed only minor changes from the untreated stressed group. These results show, probably for the first time, that (i) the endogenous histamine plays an important role in the pathophysiology of heat stress, and (ii) this effect appears to be mediated via specific histamine H2 receptors. PMID- 1436499 TI - Developmental pattern and distribution of nerve growth factor low-affinity receptor immunoreactivity in human spinal cord and dorsal root ganglia: comparison with synaptophysin, neurofilament and neuropeptide immunoreactivities. AB - Immunocytochemical expression of the low-affinity nerve growth factor receptor was studied in human fetal and adult tissues using the monoclonal antibody ME20.4. In dorsal root ganglia, a few immunoreactive neurons were first detected in nine-week-old fetuses and many more were found in the following weeks of gestation. However, none was present in adult ganglia. The ME20.4-positive cells were larger than neurons immunostained by substance P, calcitonin gene-related peptide or galanin antibodies. In the spinal cord, fibres immunostained by ME20.4 appeared in a characteristic pattern that differed from the spatial and temporal distributions of synaptophysin- and neurofilament-immunoreactive fibres. Those expressing the low-affinity nerve growth factor receptor were only detected in regions containing collaterals of primary sensory axons: (i) in the dorsal funiculus between seven and 18 weeks of gestation; (ii) in a ventrodorsal bundle reaching the ventral horn from weeks 12-14; (iii) in the medial region of the dorsal horn between weeks 12 and 20; (iv) in the superficial layers and lateral portion of the dorsal horn after the 14th week of gestation and also in adult spinal cord. During the fetal period, ME20.4 immunoreactivity was also found in motoneurons and peripheral nerve fibres in the skin, myotomes and gut. Sheaths of peripheral nerves and the adventitia of blood vessels were stained both in fetal and adult tissues. Thus, the low-affinity nerve growth factor receptor is: (i) strongly expressed in the developing human nervous system; (ii) transiently associated with a subset of large primary sensory neurons and with motoneurons; (iii) transiently and sequentially expressed by various groups of sensory afferents to the spinal cord; (iv) permanently expressed by fibres in the superficial layers of the dorsal horn, Clarke's column, nerve sheaths and the adventitia of blood vessels. PMID- 1436500 TI - Solubilization and fractionation of paired helical filaments. AB - Paired helical filaments isolated from brains of two different patients with Alzheimer's disease were extensively treated with the ionic detergent, sodium dodecyl sulphate. Filaments were solubilized at different extents, depending on the brain examined, thus suggesting the existence of two types of paired helical filaments: sodium dodecyl sulphate-soluble and insoluble filaments. In the first case, the number of structures resembling paired helical filaments greatly decreased after the detergent treatment, as observed by electron microscopy. Simultaneously, a decrease in the amount of sedimentable protein was also observed upon centrifugation of the sodium dodecyl sulfate-treated paired helical filaments. A sodium dodecyl sulphate-soluble fraction was isolated as a supernatant after low-speed centrifugation of the sodium dodecyl sulphate-treated paired helical filaments. The addition of the non-ionic detergent Nonidet-P40 to this fraction resulted in the formation of paired helical filament-like structures. When the sodium dodecyl sulphate-soluble fraction was further fractionated by high-speed centrifugation, three subfractions were observed: a supernatant, a pellet and a thin layer between these two subfractions. No paired helical filaments were observed in any of these subfractions, even after addition of Nonidet P-40. However, when they were mixed back together, the treatment with Nonidet P-40 resulted in the visualization of paired helical filament-like structures. These results suggest that at least two different components are needed for the reconstitution of paired helical filaments as determined by electron microscopy. The method described here may allow the study of the components involved in the formation of paired helical filaments and the identification of possible factors capable of blocking this process. PMID- 1436501 TI - The integrative properties of spiny distal dendrites. PMID- 1436502 TI - Immuno-electron microscopic evidence for two different types of partial somatic repair of the mutant Brattleboro vasopressin gene. AB - In homozygous Brattleboro rats a frame-shift mutation in the vasopressin gene prevents secretion of vasopressin by magnocellular neurosecretory neurons and thus causes diabetes insipidus. Whereas most "vasopressin" neurons in Brattleboro homozygotes apparently lack vasopressin and its associated neurophysin and glycopeptide, some isolated cells overcome the mutation and "revert" to producing readily detectable amounts of vasopressin. We describe here two morphologically and immunocytochemically distinct subsets of such "revertant" cells. One subset contain, in their rough endoplasmic reticulum cisterns, electron-dense aggregates immunoreactive for vasopressin, for parts of oxytocin-neurophysin, and for CP14 (a peptide with a sequence deduced from the mutated precursor), but not for vasopressin-associated glycopeptide ("glycopeptide") or vasopressin-neurophysin. In Brattleboro heterozygotes, which have one mutant and one normal copy of the vasopressin gene, morphologically similar revertant cells exist; the aggregates in the rough endoplasmic reticulum of these cells do not immuno-label for CP14, but the cells do produce 160-nm neurosecretory granules immunoreactive for vasopressin, vasopressin-neurophysin and glycopeptide. In Brattleboro homozygotes, the second, more abundant subset of neurons which recover vasopressin immunoreactivity also express vasopressin-associated glycopeptide and CP14 but not oxytocin-neurophysin; both glycopeptide and CP14 are restricted to the rough endoplasmic reticulum but do not form aggregates. We conclude that two different somatic repairs of the Brattleboro mutation can occur. We propose that, in aggregate-containing neurons, exons B and C have been exchanged between the vasopressin and oxytocin genes; glycopeptide-immunoreactive neurons have either undergone mismatch repair or exchanged exon B. PMID- 1436503 TI - Distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger RNA in the rat brain. AB - The distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger RNA was investigated in the rat brain and pituitary by in situ hybridization using a synthetic 35S-labeled oligonucleotide probe. Detection of labeled neurons by light-microscopic radioautography revealed a selective repartition of the messenger RNA-expressing cells. Several major vasoactive intestinal peptide/peptide histidine isoleucine amide messenger RNA-containing cell groups were demonstrated including layers II VI of the cerebral cortex, the suprachiasmatic nucleus and various thalamic structures such as the ventrolateral, posterior, lateral reticular, paracentralis and gelatinosus nuclei. Positive cells, to a lesser extent, were also found in the limbic system, medial preoptic area, superior and inferior colliculi as well as in the central gray matter. They were totally absent in the pituitary and the pineal gland of normal rats. The results of the present study provide a detailed mapping of neurons expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA in the adult rat brain. The predominance of vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA containing neurons in the cerebral cortex, suprachiasmatic nucleus and thalamus suggest that vasoactive intestinal peptide is mainly involved in the control of cortical informations, circadian rhythms and sensory perception in agreement with several physiological data. PMID- 1436504 TI - Lesion of the nigrostriatal pathway induces cholecystokinin messenger RNA expression in the rat striatum. An in situ hybridization histochemistry study. AB - In situ hybridization histochemistry was used to investigate the putative regulation of cholecystokinin messenger RNA expression by dopamine in the rat striatum. Using this method, cholecystokinin messenger RNA was undetectable in the normal rat striatum. Dopamine depletion caused by a 6-hydroxydopamine injection in the medical forebrain bundle induced, two and four weeks after the injection, an increase of cholecystokinin messenger RNA expression in the ipsilateral striatum. The labeling was mostly restricted to the dorsolateral quadrant. At the cellular level, this corresponded to a slight but significant labeling of a moderate density of striatal neurons which most probably represent a subpopulation of medium-sized spiny neurons. Conversely, treatment with either haloperidol or SCH23390 for two weeks did not induce any detectable changes in cholecystokinin messenger RNA expression in the striatum while, as expected, an increase in the striatal enkephalin messenger RNA content was observed. These results suggest that the dopaminergic nigrostriatal pathway directly, or indirectly, regulates the expression of cholecystokinin messenger RNA in the striatum. PMID- 1436505 TI - Kainic acid-mediated increase of preprotachykinin-A messenger RNA expression in the rat hippocampus and a region-selective attenuation by dexamethasone. AB - The hippocampus contains the highest number of glucocorticoid-sensitive neurons in the rat brain and excessive exposure to glucocorticoids can cause damage to hippocampal neurons and impair the capacity of the hippocampus to survive neuronal insults. In this study in situ hybridization combined with quantitative image analysis was used to study preprotachykinin-A mRNA levels after administration of a toxic dose of kainic acid in animals pretreated with glucocorticoids. Kainic acid was injected into dorsal hippocampus CA3 region in animals pretreated with the synthetic glucocorticoid receptor agonist dexamethasone and in control animals. Preprotachykinin-A mRNA was not detected in the hippocampus of untreated animals or in animals analysed 30 min after a kainic acid injection. However, 4 h after injection of kainic acid, the level of preprotachykinin-A mRNA increased to 20-times above the detection limit both in the dentate gyrus and the CA3 region of the hippocampus. Treatment of kainic acid injected animals with dexamethasone 30 min before and 2 h after the injection attenuated the increase in the granule cells of the dentate gyrus by 50%. In contrast, dexamethasone pretreatment had no significant effect on the kainic acid induced increase of preprotachykinin-A mRNA in pyramidal cells in regions CA3 or CA1. These results show that an excitatory stimulus within the hippocampus causes a substantial increase in the level of preprotachykinin-A mRNA in hippocampal granule and pyramidal cells and suggest that in granule cells of the dentate gyrus this increase can be modulated by glucocorticoids. PMID- 1436506 TI - A single optical fiber fluorometric device for measurement of intracellular Ca2+ concentration: its application to hippocampal neurons in vitro and in vivo. AB - We developed a new system to measure the intracellular Ca2+ concentration in the deep region of the central nervous system with a single optical fiber (300 microns in diameter), used for both excitation and detection of the fluorescence of previously loaded fura-2. With this system, a brain region loaded with fura-2 was illuminated by a rotating disc bearing three different interference filters of 340, 360 and 380 nm at a rate of 600 rpm. The emitted fluorescence was collected by the same fiber connected to a photomultiplier whose output was fed into a computer which regulates the timing of illumination and detection. The time course of the change in the fluorescence due to 340, 360 or 380 nm excitation was measured simultaneously at the maximum sampling rate of 10 points/s. Ratios of fluorescence intensities were obtained after the experiment. After confirming that this system was sensitive enough to detect the change of intracellular Ca2+ concentration in cultured hippocampal neurons and hippocampal slices during depolarization by high potassium medium (50 mM), we applied this system to anesthetized rats. In the hippocampus preloaded with fura-2, characteristic changes in fluorescence intensities ascribed to an increase in intracellular Ca2+ concentration were detected after asphyxia. The system is potentially useful for investigating the physiological and pathological roles of Ca2+ in the brain. PMID- 1436507 TI - Increased expression of c-fos in the medial preoptic area after mating in male rats: role of afferent inputs from the medial amygdala and midbrain central tegmental field. AB - Immunocytochemical methods were used to localize the protein product of the immediate-early gene, c-fos, in male rats after exposure to, or direct physical interaction with, oestrous females. Increasing amounts of physical contact with a female, with resultant olfactory-vomeronasal and/or genital-somatosensory inputs, caused corresponding increments in c-fos expression in the medial preoptic area, the caudal part of the bed nucleus of the stria terminalis, the medial amygdala, and the midbrain central tegmental field. Males bearing unilateral electrothermal lesions of the olfactory peduncle showed a significant reduction in c-fos expression in the ipsilateral medial amygdala, but not in other structures, provided their coital interaction with oestrous females was restricted to mount thrust and occasional intromissive patterns due to repeated application of lidocaine anaesthetic to the penis. No such lateralization of c-fos expression occurred in other males with unilateral olfactory lesions which were allowed to intromit and ejaculate with a female. These results suggest that olfactory inputs, possibly of vomeronasal origin, contribute to the activation of c-fos in the medial amygdala. However, lesion-induced deficits in this type of afferent input to the nervous system appear to be readily compensated for by the genital somatosensory input derived from repeated intromissions. Unilateral excitotoxic lesions of the medial preoptic area, made by infusing quinolinic acid, failed to reduce c-fos expression in the ipsilateral or contralateral medial amygdala or central tegmental field following ejaculation. By contrast, combined, unilateral excitotoxic lesions of the medial amygdala and the central tegmental field significantly reduced c-fos expression in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area after mating; no such asymmetry in c fos expression occurred when lesions were restricted to either the medial amygdala or central tegmental field. This suggests that afferent inputs from the central tegmental field (probably of genital-somatosensory origin) and from the medial amygdala (probably of olfactory-vomeronasal origin) interact to promote cellular activity, and the resultant induction of c-fos, in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area. The monitoring of neuronal c-fos expression provides an effective means of studying the role of sensory factors in governing the activity of integrated neural structures which control the expression of a complex social behaviour. PMID- 1436508 TI - Narine occlusion decreases basal levels of Fos protein in the cerebral cortex of the lizard Podarcis hispanica. AB - Immunocytochemical study of cerebral cortex of the lizard Podarcis hispanica using an antibody directed to the M peptide of the rat c-Fos protein showed a distinct pattern of Fos distribution. Abundant Fos-immunoreactive neuronal nuclei were detected in the cell layers of the medial, the dorsal and the lateral cortices, whereas only a few nuclei were found in the cell layer of the dorsomedial cortex. The Fos immunoreactivity was characterized by Western blot analysis of nuclear extracts from lizard brain and showed a distinct band with an apparent molecular weight of 30,000. In band-shift assays, nuclear extracts from lizard brain were shown to contain AP-1 complexes. The basal expression of Fos immunoreactivity is related to sensory olfactory input in the cerebral cortex of the lizard since experiments with olfactory-deprived animals resulted in a complete absence of Fos immunoreactivity in the cortical areas. PMID- 1436509 TI - Sympathetic and metabolic mechanisms of the cerebrovasomotor function of the caudal ventrolateral medulla in rats. AB - We attempted to elucidate the cerebrovasomotor function of the caudal ventrolateral medulla. Sixty-one rats were anaesthetized, paralysed and artificially ventilated. The microsphere method was employed for the measurement of blood flow. Microinjection of an antagonist of excitatory amino acids, kynurenate (2 nmol), into functionally identified depressor sites within the caudal ventrolateral medulla produced arterial hypertension of about 140 mmHg. We found that the cerebral blood flow was substantially increased, but was maintained at the same level (17 rats) as that observed under phenylephrine induced hypertension (26 rats). Bilateral severing of the cervical sympathetic trunks resulted in a further increase in blood flow in all brain regions studied (18 rats). The response was most significant in the cerebral parasagittal cortex (164 +/- 31% of baseline without, and 211 +/- 43% with sympathectomy; mean +/- S.D.; P < 0.001). The contributions of the cerebral metabolic mechanism to this flow increase under denervation was minimal, as evidenced by the observation of disproportionately smaller changes in cerebral metabolic rate for oxygen during any type of hypertension. We conclude that the cerebrovasomotor functions of the caudal ventrolateral medulla may operate to keep an equilibrium between simultaneously working tonic inhibitions against sympathetic vasoconstriction as well as against vasodilatation. This dual effect is mediated by excitatory amino acid receptors located within this particular brain area. The vasodilator mechanism may be of neurogenic origin. When the function of the brain area is suppressed, the subsequently disinhibited vasodilator mechanism dominates the cerebrovascular autoregulatory function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436510 TI - Mastoparan blockade of currents through Ca(2+)-activated K+ channels in bovine chromaffin cells. AB - The action of mastoparan (a wasp venom peptide) on "maxi" Ca(2+)-activated K+ channels was studied in excised inside-out patch recordings from cultured bovine chromaffin cells, under normal conditions (160 mM K+ inside, 154 mM Na+ outside). Mastoparan, when applied on the intracellular side of the membrane reduced the open channel probability in a concentration dependent manner. Changes in the channel kinetics were complex. The histograms of the open dwell times were all described by either one or two exponentials. Mastoparan shortened the mean duration of the major (long) component and to a lesser extent the minor (short) component. Closed dwell times, were described by three exponentials. While the short (major) component was prolonged by mastoparan, and the intermediate component was unaffected, the long component was shortened. Overall mean closed times were prolonged. The changes in channel kinetics could only partly be explained by a channel-blocking mechanism, even when assuming that mastoparan acts as both an intermediate and a slow channel blocker suggesting that it affects gating mechanism. The fact that mastoparan is a calmodulin inhibitor and a G-protein activator raises the possibility that in bovine chromaffin cells, either the membrane-bound calmodulin or a G-protein, plays a role in the modulation of Ca(2+)-activated K+ channels. PMID- 1436511 TI - In vivo release of calcitonin gene-related peptide-like material from the cervicotrigeminal area in the rat. Effects of electrical and noxious stimulations of the muzzle. AB - The continuous perfusion with an artificial cerebrospinal fluid of the cervicotrigeminal area of the spinal cord in halothane-anaesthetized rats allowed the collection of calcitonin gene-related peptide-like material with the same immunological and chromatographic characteristics as authentic rat alpha calcitonin gene-related peptide. The spinal release of calcitonin gene-related peptide-like material could be significantly increased by the local application of 60 mM K+ (approximately +100%), high-intensity percutaneous electrical stimulation (approximately +200%) and noxious heat (by immersion in water at 52 degrees C; approximately +150%) applied to the muzzle. By contrast, noxious mechanical (pinches) and chemical (subcutaneous formalin injection) stimulations and deep cooling (by immersion in water at 0 degrees C) of the muzzle did not alter the spinal release of calcitonin gene-related peptide-like material. In addition, low-intensity electrical stimulation, recruiting only the A alpha/beta primary afferent fibres, significantly reduced (approximately -30%) the release of calcitonin gene-related peptide-like material from the cervicotrigeminal area. These data suggest that among the various types of natural noxious stimuli, noxious heat may selectively excite calcitonin gene-related peptide-containing A delta and C primary afferent fibres projecting within the dorsal horn of the spinal cord, and that activation of A alpha/beta fibres reduces spontaneous calcitonin gene-related peptide-like material release possibly through an inhibitory presynaptic control of calcitonin gene-related peptide-containing A delta/C fibres. PMID- 1436512 TI - Rules of combination that generate climbing fiber tactile receptive fields. AB - Climbing fiber tactile receptive fields in the anterior lobe of the cat's cerebellum are found to have regularities of shape, independent of their relative position on the cerebellar cortex. The shape regularities can be expressed as rules of combination that generate the receptive field shapes. Both face and paw receptive fields are unions of a certain set of skin areas called compartments. Face receptive fields are generated by taking the union of a seed compartment and another compartment in a binary relation to it, called CF-contiguity. Paw receptive fields are formed in a similar iterative fashion, with the constraint that anatomically equivalent areas be included on all toes involved in the receptive field. This paper specifies rules of combination that both reproduce observed receptive fields and also predict receptive fields that have not yet been observed. Because of the regularities of shape among the climbing fiber tactile receptive fields, the rules of combination can be used to predict ensemble activation in response to tactile stimulation. PMID- 1436513 TI - Lack of association between Alzheimer's disease and education, occupation, marital status, or living arrangement. AB - Using the resources of the Rochester Epidemiology Project, we conducted a case control study of sociodemographic characteristics using the incidence cohort of patients with Alzheimer's disease (AD). During the conduct of ongoing studies of AD in Rochester, we identified new cases of AD as they occurred during 1975-1979 (N = 241). We selected one age- and sex-matched control from among all registrations for care in this community during the year of onset for each case. There was little difference between cases and controls for educational attainment, marital status, type of dwelling, living arrangement, or occupation. We were unable to confirm low educational level as a risk factor for AD in this population. Future attempts to identify etiologic risk factors for dementing illness should probably move toward other areas of research. PMID- 1436514 TI - A dynamic posturography study of balance in healthy elderly. AB - Using dynamic posturography, we studied the balance of 234 community-dwelling elderly subjects (mean age, 76 +/- 5 years) as well as 34 young controls (mean age, 34 +/- 12 years). Almost all measures of balance were worse in elderly subjects compared with young controls. The decrements in older persons indicate a diminished capacity to process conflicting sensory input as well as a possible narrowing of the limit of stability (or, alternatively, an increase in sway). We propose that this occurs most likely as a result of biomechanical or central processing changes as opposed to diminished sensory or vestibular input. Furthermore, with difficult tasks sequentially presented, the performance of the older subjects improved, suggesting that balance, at least in the short term, adapts to stressful conditions. In these elderly subjects screened for age related diseases affecting balance, only small decrements of balance occurred between the ages of 70 and 85 years. This nominal decrease over a 15-year span suggests that clinically significant balance impairment is the result of age related disease rather than an inevitable consequence of aging and is therefore potentially treatable. PMID- 1436515 TI - Influence of additional information on interrater reliability in the neurologic examination. AB - We performed a routine neurologic examination on 200 patients who were reexamined by a second physician under three different conditions: (1) reexamination of only one item, (2) complete reexamination without knowledge of the patient's history and complaints, and (3) complete reexamination with such knowledge. We used changes in reliability as an index of the effect of additional information on basic data collection. Additional information increased reliability, indicating that diagnostic hypotheses obtained mainly from the history improve the examiner's precision. When a complete reexamination was performed with knowledge of the patient's history, reliability was substantial (kappa > 0.6). More experienced examiners do not perform the examination more reliably, but do utilize the patient's history differently. PMID- 1436516 TI - Acute quadriplegic myopathy: a complication of treatment with steroids, nondepolarizing blocking agents, or both. AB - We studied two patients who were given high-dose intravenous steroid therapy and were intubated for status asthmaticus. Both became quadriplegic and wasted within 2 weeks. EMG had myopathic abnormalities. Muscle biopsy revealed severe atrophy of most muscle fibers, with disorganization of myofibrils and selective loss of thick (myosin) filaments. Immunohistologic stains for myosin isoforms confirmed the decrease or absence of this protein. Both patients clinically improved over several months. PMID- 1436517 TI - Familial amyloidotic polyneuropathy presenting with carpal tunnel syndrome and a new transthyretin mutation, asparagine 70. AB - We report familial amyloidotic polyneuropathy in a pedigree of German ancestry residing in New Jersey. Eight affected subjects presented in the third to seventh decade with carpal tunnel syndrome (CTS) and one subject presented with vitreous opacification. Transmission was autosomal dominant and survival was prolonged. Affected subjects were heterozygous for a novel mutation in serum transthyretin (TTR), resulting in an asparagine for lysine substitution at residue 70 of the TTR monomer. We report two methods for rapid identification of the mutation based on the polymerase chain reaction. This pedigree further emphasizes the evolving phenotypic and genotypic heterogeneity of the transthyretinopathies. Familial or sporadic CTS or unexplained vitreous opacification suggest the possibility of TTR amyloidosis and should prompt a search for TTR mutations. PMID- 1436518 TI - Mononeuritis multiplex associated with cryoglobulinemia in HIV infection. AB - We describe a patient with human immunodeficiency virus (HIV) infection who developed mononeuritis multiplex associated with polyclonal (type III) cryoglobulinemia. The patient's symptoms stabilized following treatment with plasmapheresis and removal of the cryoglobulin. Our case represents the first report of polyclonal cryoglobulinemia in HIV disease and suggests that cryoglobulinemia may play an etiologic role in some patients with HIV-associated neuropathy. PMID- 1436519 TI - Age-related loss of dorsal vagal neurons in Parkinson's disease. AB - Older patients who die with Parkinson's disease (PD) have fewer pigmented neurons in the locus coeruleus and fewer substance P-containing neurons in mesopontine tegmental nuclei. We analyzed two other medullary nuclei, the dorsal vagal nucleus and the hypoglossal nucleus, in eight PD patients and six normal controls by counting neurons in serial Nissl stained sections to determine the relationship between age at death and cell loss in these nuclei. PD-related neurodegenerative changes (Lewy bodies and neuronal loss) were present only in the dorsal vagal nucleus (13,637 +/- 1,323 neurons in PD, 24,885 +/- 1,157 in normal controls). Cells in the intermediate rostrocaudal part of the nucleus were most severely affected. There was a significant correlation between loss of vagal neurons and age at death in PD patients. No age-related cell loss was present in the dorsal vagal nucleus of normal brains, or in the hypoglossal nucleus in either PD or normal brains. These results confirm that age-related cell death depends on whether or not there is coexistent PD. PMID- 1436520 TI - Markers of dopamine metabolism in Parkinson's disease. The Parkinson Study Group. AB - We used two analytic methods (a multichannel coulometric electrode array with high-performance liquid chromatography, and gas chromatography-mass spectrophotometry) to measure CSF dopamine (DA) and its metabolites in mildly affected, unmedicated subjects with Parkinson's disease (PD). The mean (+/- SD) concentration of homovanillic acid (HVA), the most abundant product of DA turnover, was 164.57 +/- 95.05 nM. As sequential aliquots of CSF were collected from the first to 23rd ml, CSF HVA concentration almost doubled. After HVA, 3-O methyldopa (3-O-MD) was the next most abundant compound. The summed concentrations of 3-O-MD, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, DA, DA-3-sulfate, homovanillol, and levodopa (LD) amounted to 12.6% of HVA. Concentrations of the DA metabolites did not correlate to a variety of indices of PD severity. The presence of LD and 3-O-MD may be indicators of DA synthesis and possibly could reflect compensatory processes among surviving dopaminergic neurons of the PD brain. PMID- 1436521 TI - A 17th-century founder gives rise to a large north American pedigree of autosomal dominant spinocerebellar ataxia not linked to the SCA1 locus on chromosome 6. AB - There have been three reports since 1969 of members of a "W" family with autosomal dominant spinocerebellar ataxia (SCA), and various conclusions have been drawn about the nosology. This pedigree has been traced back over 300 years through 11 generations. Although phenotypically similar to the disorder in the Schut-Swier, Nino, and other kindreds, the disorder in the W family is not linked to the SCA1 locus on chromosome 6, as reported in those hereditary ataxia pedigrees. The W family represents the largest such North American kindred yet reported. We examined 33 family members of a distantly related branch of the W family, determined the cumulative age of onset, and projected the number of present-day gene carriers. Two cases illustrate the spectrum of symptoms among family members. Age of onset and presenting symptom, however, seem to correlate both in our patients and in those previously reported. Between 2,000 and 5,000 individuals are estimated to be at risk of developing the disorder within this pedigree alone. The pedigree reported here will be valuable in the identification and cloning of a gene for hereditary ataxia, designated "SCA2" at the Eleventh International Workshop on Human Gene Mapping. PMID- 1436522 TI - Patterns of cerebral atrophy in HIV-1-infected individuals: results of a quantitative MRI analysis. AB - Cerebral atrophy is a common radiologic manifestation of HIV dementia. To evaluate the relationship between cognitive impairment and cerebral atrophy, adjusting for age and immune status, we used standardized planimetry to measure the ventricle-brain ratio (VBR) and the bifrontal (BFR) and bicaudate (BCR) ratios, three measures of cerebral atrophy. We analyzed cranial MRIs of 23 HIV-1 seronegative controls (SN) and 116 HIV-1-infected individuals. Of the HIV-1 seropositive individuals, 37 had HIV dementia (DM group), 40 had neurologic or neuropsychological abnormalities insufficient for HIV dementia (NP+ group), and 39 were neurologically normal (NML group). We performed comparisons using analysis of covariance with correction for multiple comparisons. Both the VBR, a general measure of overall cerebral atrophy, and the BCR, a measure of atrophy in the region of the caudate nucleus, are significantly associated with dementia. The association is stronger for BCR enlargement than for VBR enlargement, suggesting that selective caudate region atrophy is associated with HIV dementia. These results indicate that overall cerebral atrophy and prominent caudate region atrophy are important radiographic features of HIV dementia. PMID- 1436523 TI - Amyloid angiopathy in diffuse Lewy body disease. AB - We determined the frequency of cerebral amyloid angiopathy (CAA) in 135 consecutive cases of diffuse Lewy body disease (DLBD) (N = 67), Alzheimer's disease (AD) (N = 34), and normal elderly controls (NECs) (N = 34). DLBD cases were subdivided into those with pathologic changes compatible with coexistent AD (DLBD/AD) and those without sufficient AD-type changes to warrant that diagnosis. In each case, we assessed the frequency, severity, and distribution of CAA on multiple thioflavin-S-stained sections of cerebral cortex examined with fluorescent microscopy. Based on immunocytochemistry with beta-amyloid antibodies, amyloid in all the brains was composed of beta/A4. CAA was present in the leptomeningeal vessels in 50% of the NECs and in 100% of AD cases. In DLBD without coexisting AD, the frequency of leptomeningeal CAA was 58%, whereas in DLBD/AD, the frequency was 85%. The frequency of CAA in parenchymal vessels was 38% for NECs, 97% for AD, 43% for DLBD, and 85% for DLBD/AD. There was no significant difference in the frequency or severity of CAA between NECs and DLBD, but CAA was significantly more severe, and comparable with CAA in AD, in the cases of DLBD/AD. Ten NECs had focal CAA without senile plaques (SPs), whereas all other cases with CAA had at least some SPs. Neither CAA nor SPs were present in 14 cases, including seven NECs and seven DLBD cases. We found cerebrovascular accidents in 50 cases (including nine without CAA) and leukoencephalopathy in 24 cases. These results suggest that CAA and other AD-type changes are not concomitant with DLBD but are related to coexisting AD or pathologic aging. PMID- 1436524 TI - Intracranial EEG study of brain structures affected by internal carotid injection of amobarbital. AB - Hippocampal function, considered critical in memory processing, is supposedly tested in the intracarotid sodium amobarbital (ISA) procedure; however, since the hippocampus is not completely irrigated by the internal carotid artery, some believe the procedure may be invalid for memory testing. We quantified delta activity in intracerebral EEGs during ISA tests. There was increased delta in ipsilateral structures as follows: amygdala (6.4 minutes), anterior hippocampus (7.2), middle hippocampus (7.4), temporal neocortex (9.1), frontal lobe (8.4), central/parietal area (11.0), and occipital lobe (9.7). Contralateral structures usually (> 64%) showed increased delta lasting 4 to 5 minutes. The ipsilateral hippocampus had delta waves in over 90% of injections. We conclude that the hippocampus is clearly affected by the ISA injection. We argue that the slow waves may not be caused by a direct effect of the drug, but rather by a functional deafferentation due to the profound inactivation of structures surrounding the hippocampus. Similarly, slow waves contralateral to injection may be caused by sudden removal of neuronal input from the regions receiving the amobarbital. PMID- 1436525 TI - Rapid postanoxic calcification of the basal ganglia. AB - A 22-year-old male diabetic on hemodialysis suffered a cerebral anoxic event. Serial CT showed the development of basal ganglia calcification over a period of no more than 17 days. It appears that the basal ganglia may develop petechial hemorrhage, necrosis, calcification, or combinations of these following an anoxic insult. The neuropathologic substrate and mechanism of rapid postanoxic calcification are unknown. PMID- 1436526 TI - MELAS syndrome with mitochondrial tRNA(Leu)(UUR) mutation: correlation of clinical state, nerve conduction, and muscle 31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin. AB - We report a patient with mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes treated with riboflavin and nicotinamide for 18 months, during which time previously frequent encephalopathic spells ceased. To confirm clinical benefit, we withdrew treatment and monitored response with muscle 31P magnetic resonance spectroscopy (MRS) and sural nerve conduction studies. Of three prospectively chosen MRS variables, two changed coincidentally with clinical end points; phosphocreatine (PCr)/adenosine triphosphate recovery rates fell in parallel with sural nerve sensory amplitudes, and a drop in muscle bioenergetic efficiency (relationship of inorganic phosphate/PCr to the accelerating force of contracting muscle) coincided with development of encephalopathy. Investigations revealed a deficiency of respiratory complex I and mutation of the mitochondrial tRNA(Leu)(UUR). We suggest that a defective cellular energy state in mitochondrial disease may be partially treatable and that changes seen in appropriate muscle spectroscopy studies may parallel improvement in brain and peripheral nerve function. PMID- 1436527 TI - Changes in lymphocyte subsets in myasthenia gravis: correlation with level of antibodies to acetylcholine receptor and age of patient. AB - We report a detailed analysis of the subsets of lymphocytes in patients with myasthenia gravis (MG). There was a slight, nonsignificant increase in the level of CD5+ B lymphocytes among MG patients as compared with normal controls. The proportion of CD5+ T cells in MG was similar to that in controls. However, whereas age had no effect on the level of these cells in normal individuals, a significant age-related decrease of these cells was present in MG patients. The proportion of double-positive CD4+CD8+ T cells was significantly increased in MG. The level of the CD29+CD4+ (helper-inducer) subset was significantly higher in MG patients than in controls. There was no correlation between the titer of autoantibodies to acetylcholine receptor and the level of either CD29+CD4+ T cells or CD5+ B cells among MG patients. The only T-cell subset that correlated with the autoantibody titer was the CD45RA+CD4+ (suppressor-inducer) subset of CD4+ T cells. PMID- 1436528 TI - Diagnosis of familial hypokalemic periodic paralysis: role of the potassium exercise test. AB - Familial hypokalemic periodic paralysis (FHOPP) is a rare, dominantly inherited disease, the diagnosis of which may require the induction of paralysis. We studied whether the increase in plasma potassium concentration during exercise can be used in the diagnosis of FHOPP. Potassium concentration increased 0.3 +/- 0.1 mEq/l in patients with FHOPP and 0.6 +/- 0.1 mEq/l in healthy controls (p < 0.001) during a 10-minute bicycle exercise test, and 0.3 +/- 0.1 mEq/l in patients with FHOPP and 0.8 +/- 0.2 mEq/l in healthy controls (p < 0.001) during a 30-minute bicycle exercise test. We conclude that the potassium exercise test may be useful in the diagnosis of FHOPP. PMID- 1436529 TI - Recurrent inhibition is increased in patients with spinal cord injury. AB - Mechanisms underlying the development of spasticity after spinal cord injury are not understood. One spinal interneuron likely to be affected is the Renshaw cell, which acts to produce recurrent inhibition in motor neurons as well as inhibiting Ia interneurons. Descending pathways exert both excitatory and inhibitory control over Renshaw cell activity. We studied Renshaw cell activity in normal subjects and in patients with varying levels of spasticity after spinal cord injury using the conditioned H-reflex technique of Pierrot-Deseilligny and Bussel. A submaximal stimulus to the tibial nerve is presented prior to a supramaximal stimulus so that action potential collision permits an H reflex (H') to be elicited in response to the supramaximal stimulus. The amplitude of this H' reflex is affected by activity in recurrent inhibitory pathways. Patients with both complete and partial spinal cord lesions were studied; date of injury ranged from 1 month to 216 months prior to evaluation. In the 18 patients in whom H reflexes could be recorded, H' reflexes were absent in 13, in contrast to their uniform presence in normal subjects. We conclude that recurrent inhibition via Renshaw cell activity is increased in spinal cord injury, and that measures of recurrent inhibition may correlate well with some clinical measures of spasticity. PMID- 1436530 TI - Subacute necrotizing encephalopathy: oxidative phosphorylation defects and the ATPase 6 point mutation. AB - Subacute necrotizing encephalopathy (SNE) or Leigh's disease is associated with various defects in oxidative phosphorylation (OXPHOS). However, the relationships between these OXPHOS defects and nuclear DNA or mitochondrial DNA (mtDNA) mutations is still unclear. We evaluated three SNE pedigrees (two singleton cases and a pedigree) biochemically for OXPHOS abnormalities and genetically for four mtDNA point mutations. There was a complex I defect in all three pedigrees that was associated with a complex III defect in two individuals. An mtDNA mutation in the ATPase, subunit 6 gene (np 8993) was present in one SNE pedigree. This mutation was maternally inherited, heteroplasmic, produced marked clinical and biochemical heterogeneity between pedigree members, and varied along the maternal lineage at levels ranging from 0% to > 95% of the total mtDNAs. These mtDNA mutations were not present in the other two pedigrees. These observations emphasize the importance of screening for OXPHOS defects and mtDNA mutations in SNE cases. PMID- 1436531 TI - Long-term neuromuscular dysfunction produced by passive transfer of amyotrophic lateral sclerosis immunoglobulins. AB - We investigated the role of the immune system in the pathogenesis of amyotrophic lateral sclerosis (ALS) by studying the long-term consequences of ALS immunoglobulin (Ig) application on the levator auris muscle of the mouse. We applied Ig from seven ALS patients, four disease controls, and a pool of normal Ig (6 mg of Ig in 2 weeks) by subcutaneous injection; removed the muscles 4 to 12 weeks after the beginning of treatment; and recorded both spontaneous and evoked release of transmitter. None of the control Ig induced changes in transmitter, whereas five of seven ALS Ig induced a significant increase in the rate of spontaneous release, and all ALS Ig produced significant changes in the quantal content of evoked release. In muscles treated with one of the ALS Igs, synaptic activity was completely absent. Cholinesterase and silver staining demonstrated intact neuromuscular junctions in the control Ig-treated muscles and also in many areas of ALS Ig-treated muscles. Axonal degeneration and denervation were present in most muscles treated with ALS Ig. There was complete denervation when no synaptic activity could be recorded. Thus, ALS Ig appears to lead to long-lasting effects at the neuromuscular junction, and such effects may be an early stage in the immune-mediated pathogenesis of ALS. PMID- 1436532 TI - X-linked spinomuscular atrophy: a kindred with associated abnormal androgen receptor binding. AB - We studied androgen receptor function in cultured scrotal skin fibroblasts from eight subjects with X-linked spinal and bulbar muscular atrophy (SBMA) (Kennedy's syndrome) from four families. The neuromuscular and endocrine features were similar in all patients. High-affinity dihydrotestosterone binding (Bmax) was decreased in three patients from one family (average, 11.1 fmol/mg) similar to values in subjects with androgen resistance syndromes. Bmax was normal in five SBMA patients from three other families (average, 26.0 fmol/mg). This finding provides direct evidence for abnormal androgen receptor function in some patients with SBMA. There was some correlation between severity of neuromuscular and endocrine dysfunction, providing further evidence that the two types of manifestations are related. PMID- 1436533 TI - Western blotting in evaluating Lyme seropositivity and the utility of a gel densitometric approach. AB - The antibody response to Borrelia burgdorferi is widely used in the diagnosis of Lyme neuroborreliosis and other manifestations of Lyme disease. However, a problem with immunoassays has been a significant number of false positives. The Western blotting technique is a useful adjunct in the serodiagnosis of other infections, but its use in Lyme borreliosis has been limited because of a lack of definition of what constitutes a positive assay. Using a gel densitometric analysis, we devised quantitative criteria for positivity and tested our criteria by matching blot results with clinical characteristics in a retrospectively studied group of 20 patients with Lyme disease, 23 healthy controls, and 18 patients with other neurologic and rheumatologic diseases. We then evaluated these criteria prospectively in serum from 35 ELISA-positive patients, and found that the serum from the majority of patients with positive serologies by ELISA were negative by Western blot. The Western blot-negative seropositive patients usually had other inflammatory or infectious diseases. We conclude that quantitative Western blotting is a helpful test in the serodiagnosis of Lyme neuroborreliosis and other manifestations of Lyme disease. PMID- 1436534 TI - Ataxia in epidural spinal cord compression. AB - Nine patients presented with ataxia as the primary manifestation of epidural spinal cord compression. Eight had known cancer, the ninth an epidural abscess. Lower-extremity dysmetria, gait ataxia, or both, were the only neurologic signs in five patients. An incorrect initial diagnosis led to delay in treatment and subsequent neurologic deterioration in six patients. Failure to recognize isolated, painless ataxia as the initial manifestation of spinal cord compression and appropriately treat the disorder can result in irreversible spinal cord deterioration. PMID- 1436535 TI - Aphasia in multiple sclerosis: clinical and radiologic correlations. AB - Aphasia is not commonly reported in multiple sclerosis (MS). We report on two clinically definite MS patients, with a remitting-relapsing course, who presented with acute onset of aphasia. MRI demonstrated giant plaques in the left frontal region in one and in the left centrum semiovale in the other. These lesions were not evident in MRI performed several months previously, and may account for the aphasia. In both patients, language functions markedly improved within several weeks. In one patient, follow-up MRI 3 months later revealed a moderate reduction in the size of the plaque. PMID- 1436536 TI - Prolonged absence status epilepticus associated with carbamazepine therapy, increased intracranial pressure, and transient MRI abnormalities. AB - We describe an adolescent epileptic patient who presented in nonconvulsive status epilepticus that appeared to be related to treatment with carbamazepine. The absence status, which was resistant to multiple anticonvulsants, produced increased intracranial pressure and transient abnormalities observed on MRI. PMID- 1436537 TI - HMSN III phenotype due to homozygous expression of a dominant HMSN II gene. AB - We describe two siblings with hereditary motor and sensory neuropathy (HMSN) type III. Their parents were both affected with autosomal dominant axonal HMSN. The neuropathy in the siblings probably resulted from homozygous expression of the HMSN II gene. Together with other reports of homozygous HMSN I, this family suggests that HMSN III is heterogenous and encompasses the most severe homozygous expression of neuropathic genes. PMID- 1436538 TI - Failure of high-dose heparin to prevent recurrent cardioembolic strokes in a pregnant patient with a mechanical heart valve. AB - A 27-year-old woman with a mechanical heart valve suffered multiple thromboembolic events while pregnant despite anticoagulation with high-dose heparin. Warfarin, the anti-coagulant of choice for patients with prosthetic heart valves, is teratogenic and can cause hemorrhagic complications at delivery. Heparin reduces thromboembolic complications, but is of uncertain efficacy. We discuss alternatives for the prevention of thromboembolic complications in pregnant women with mechanical heart valves. PMID- 1436539 TI - Aphasic seizure caused by focal epilepsy in the left fusiform gyrus. AB - We report a patient with paroxysmal aphasia evoked by ictal epileptiform discharges localized to the left fusiform gyrus, where a small brain tumor existed. The intracranial EEG recordings during other seizures demonstrated a close functional link between the left fusiform gyrus and Wernicke's area. The patient also showed transient aphasia with electrical stimulation of the left fusiform gyrus. PMID- 1436540 TI - Neutralizing antibodies against HTLV-I in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and asymptomatic carriers. AB - We tested serum specimens from patients with HAM/TSP and asymptomatic HTLV-I carriers from endemic areas of Japan, Jamaica, Colombia, and Chile for neutralizing antibodies against HTLV-I. The data suggest a trend for neutralizing activity to be found more frequently in the sera from HAM/TSP patients than in sera from asymptomatic carriers. The result of this study emphasizes the importance of determining biologic properties of the envelope glycoprotein of HTLV-I. PMID- 1436541 TI - Needle muscle biopsy with the automatic Biopty instrument. AB - Needle muscle biopsies are less traumatic and easier to do than open biopsies, but their main disadvantage is the small specimen size. One hundred and five patients underwent needle biopsies with a 14-gauge spring-loaded device that guillotines the muscle automatically (Bard Radiology). Fifty patients had more than one muscle biopsy. One hundred and forty-six of 155 specimens contained over 200 muscle fibers, some as many as 500 fibers. Having evaluated various needles, we found the Bard Biopty instrument more efficient than manual needles and open biopsy techniques, and it provides muscle specimens for pathologic interpretation that are comparable with open surgical procedures. PMID- 1436542 TI - Racial hygiene, active euthanasia, and Julius Hallervorden. PMID- 1436543 TI - Temporary reversal of cord compression with hyperosmolar glucose. PMID- 1436544 TI - Giant axonal neuropathy: progressive clinical and radiologic CNS involvement. PMID- 1436545 TI - Ictal bradycardia with syncope: a case report. PMID- 1436546 TI - Neurologic sequelae of thinking: compression neuropathies caused by a specific posture. PMID- 1436547 TI - Neuralgia preceding recurrent herpes simplex virus type 2 whitlow. PMID- 1436548 TI - High frequency of hemorrhagic strokes in Jerusalem during the Persian Gulf War. PMID- 1436549 TI - Isolated abducens nerve palsy from pontine infarction in a diabetic patient. PMID- 1436550 TI - Thymus, antibodies, and myasthenia. PMID- 1436551 TI - Secondary torticollis. PMID- 1436552 TI - Lead exposure and ALS. PMID- 1436553 TI - Reversible motor neuron disease. PMID- 1436554 TI - Multifocal motor neuropathy. PMID- 1436555 TI - HTLV-I myelopathy. PMID- 1436556 TI - Vascular dementia. PMID- 1436557 TI - [Respiratory function tests and operative risk in thoracic surgery]. AB - In a retrospective study on 145 patients who underwent anesthesia for thoracic surgery, perioperative variables and preoperative pulmonary function tests influencing mortality and morbidity were evaluated. 3 patients (2.07%) died and 6 (4.14%) had cardiac, respiratory and other complications in postoperative 48 hours. Clinical-statistic analysis has shown the perioperative variables predictive on mortality and morbidity and operative risk: the operation type, FEV1, MVV (% theoretical), postexclusion gas analysis, Motley index (TLC/RV), intraoperative PaCO2, muscle-relaxant dose, preoperative myocardial infarction, weight, ASA, abnormal ECG, hypercreatininemia and loss of blood. MVV, FEV1, Motley index and residual FEV1 are the useful preoperative pulmonary function tests for evaluation of operative risk and surgical resection. Evaluation of operative risk in thoracic surgery shows the necessity of preoperative pulmonary function tests. PMID- 1436559 TI - [Problems related to resuscitation in studies with contrast media]. AB - This study has the purpose of describing indications and legal implications related to the intravascular use of contrast media (ICM) in order to provide useful guidelines to the intensivist, often involved in the treatment of adverse reactions. The structure of modern contrast media (CM), is a benzenic ring carrying steadily three iodine ions. Adverse reactions due to the use of ICM, are local or systemic ranging from skin rashes or flushes (urticaria et al.), to cardiovascular, respiratory and neurologic symptoms. The prevention of these reactions is mandatory in patients reporting a history of allergy or atopia disease. From a legal point of view, the contraindication to procedures involving i.v. use of CM are not clearly pointed out therefore several concerns have been expressed. The intensivist is not required to physically attend the procedure, in agreement with the circular #64 edited in 1979; on the other hand his prompt intervention should be granted if necessary. Furthermore every therapeutic supply suitable for any resuscitational intervention should be available in the area where the test is performed. In conclusion we would like to stress the financial and ethic implications related to the choice of ICM (ionic versus non-ionic). The use of non-ionic CM offers several advantages: among them the better tolerance for the patient and the lower incidence of adverse reactions. However non-ionic CM have a cost ten-fold higher and both groups of drugs have same incidence of fatal reactions, therefore the use of non-ionic ICM is recommended for high risk patients. PMID- 1436558 TI - [Determination of the best amino acid input after orthotopic liver transplantation]. AB - Ten-three patients were investigated during the early postoperative phase after orthotopic liver transplantation to assess the adequacy of the amino acid (AA) supply during both parenteral (days 1-5) and enteral (days 6-9) nutrition. Plasma AA profile was determined preoperatively, on day 4 and 5 during TPN and on day 8 and 9 during EN, urea production rate was measured every day. Calories input was 28 kcal.kg-.day as glucose, nitrogen intake was 0.25 g.kg- day, supplying individual AA on the basis of previous studies. Urea nitrogen production during TPN (9-11 gN/m2.day) outlines the ability of the transplanted liver to manage the overall nitrogen load. Individual AA plasma profile was considered the expression of an adequate input when comprised between 1 and 1.5 times the normal value, in this respect we obtained adequate levels of all essential AAs. Particularly phenylalanine, methionine and branched chain AA, critical during liver failure, were kept in this range by supplying 68, 48 and 500 mg.kg-1.day. According to AA profile the supply of cystine and tyrosine (conditionally essential AAs), and of histidine, taurine, proline and serine could be safely increased. Not given dispensable AAs (glutamine, asparagine, citrulline and alfa amino butyric) showed a plasma level below the norm and should be added to the diet. PMID- 1436560 TI - [Sleep disorders in patients in recovery. Preliminary results in 20 patients]. AB - Various aspects of the critically ill patient sharing pain, physical distress, anxiety, environmental components, predispose him to develop some sleep disorders (SD). We studied 20 conscious patients, age 16-80 (mean 48.15 SD of mean +/- 25), undergoing ICU mean 14.3 days (SD of mean +/- 7.5), to evaluate SD rate and their possible leading causes. Through Spearman Rank test SD was related to Apache II score, admission state anxiety, satisfactory sedation, days of ICU stay and age respectively. Conclusive results showed SD rate in all our patients. Excepted a statistical trend to significativity of SD versus satisfactory sedation: RS 0.311 (threshold value for 20 patients: 0.377), no relation was found between SD and data recorded. These preliminary results emphasize the importance of looking for SD in ICU patients though many factors may play a role to develop them. PMID- 1436561 TI - [Neuropsychologic effects of anesthesia in the elderly]. AB - Two anaesthetic techniques, the general balanced anaesthesia and the spinal one, have been compared in relation to their effects on neuropsychological functions as assessed by a neuropsychological test battery. Seventeen patients, who underwent different kinds of operations, have been kept under observation and checked up from a neuropsychological point of view 3 days before (time A) and 7 and 30 days after the operation (respectively time B and time C). No statistical significant differences in relation to the two anaesthetic techniques were found when comparing A, B and C assessment times. A decrease in cognitive performance at time B and a gradual return to basal condition were observed in patients who underwent general anaesthesia. Nevertheless the lack of statistical significance of the observed data leads to the need for further investigation. PMID- 1436562 TI - [New duties for anesthetists in blood transfusion]. AB - The Authors discuss new duties assigned to anaesthetist-resuscitators by Italian transfusional law (107/90, D.M. 27.12.90, Technical Directions). Preoperative hemodilution is the main task, and the need for the anaesthetist to perform it autonomously has important medical-legal consequences. PMID- 1436563 TI - [The use of nefopam in the prophylaxis and treatment of postoperative shivering]. AB - Chlorhydrate nefopam was used in the prophylaxis and treatment of postoperative shivering in 54 patients undergoing general anesthesia for radical cystectomy with trans-intestinal anastomosis. Postoperative shivering was not observed in any of the patients treated with nefopam before coming round, whereas it occurred in 55% of patients treated with placebo. Chlorhydrate nefopam subsequently stopped shivering in all these patients. The main side effects observed took the form of delayed awakening in 11% of patients receiving prophylactic treatment and somnolence lasting 5-10 minutes in all other patients. PMID- 1436564 TI - [The use of propofol in status epilepticus]. AB - Three cases of status epilepticus not responsive to an aggressive treatment are described. The seizures and EEG activity were rapidly brought under control with a continuous infusion of propofol (3-6 mg/kg/hour), maintained between 21 hours and 7 days. Patient awakening at the end of the infusion period was rapid and without sequelae. PMID- 1436565 TI - [Resistance to non-depolarizing myorelaxants. Our experience with 3 clinical cases]. AB - The Authors report their own experience in three patients that showed reduced sensitivity to atracurium or vecuronium. Two patients were affected by neoplastic diseases and one by hand trauma. Doses of 0.5 mg/kg of atracurium and 0.08 mg/kg of vecuronium were unable to establish a complete neuromuscular blockade. The Authors review the main clinical situations in which resistance to non depolarizing muscle relaxants is known: burns, hepatic diseases, chronic therapy with anticonvulsant drugs. Possibly, such events are due to fast elimination of the drug, or to an increased number of acetylcholine nicotinic receptors, or to an unknown acutely acting circulating factor, or to increased binding of the drug to plasma proteins. Up to date, no well-established explanation is available. PMID- 1436566 TI - [Hepatocystic ducts: anatomic curiosity or surgical challenge?]. AB - The Authors report two cases of cysto-hepatic ducts. Clinical and therapeutic patterns of this rare biliary disease are stressed, underlining the surgical hazard related to iatrogenic damage of bile ducts during operative manoeuvres. PMID- 1436567 TI - [Paradigmatic endoscopic features of diverticular disease of the colon]. PMID- 1436568 TI - [Costo-clavicular outlet syndrome]. AB - Syndromes caused by the compression of the neurovascular bundle are not a rare pathology, though their exact frequency cannot be assessed. Neurovascular bundle in the upper limbs may be compressed at the costo-clavicular space, interscalene triangle or at the insertion of the minor pectoralis muscle into the coracoid process. More than 90% of patients present neurological symptoms and 10% also have vascular problems. Diagnosis depends on a careful clinical and instrumental study of the patients. Arteriography, phlebography and Doppler tests were of value in the diagnostic approach, showing the compression of the subclavian artery and vein using the arm abduction manoeuvre. Electromyography is of value in differential diagnosis of the carpal tunnel syndrome showing the entity and site of nerve compression. The best form of surgical treatment is resection of the first rib according to Roos, using an extrapleural and transaxillary route. PMID- 1436569 TI - [Leiomyoma associated with esophageal diverticulosis]. AB - The Authors report a case of leiomyoma located in an epi-phrenic diverticulum. The development of the leiomyoma may have weakened the esophageal wall and caused the diverticulum to appear. Surgical treatment consisted of diverticulectomy with myotomy and a Belsey MK IV antireflux procedure. PMID- 1436570 TI - [Local recurrence after gastrectomy for cancer. Presentation of 2 clinical cases]. AB - The Authors report two cases with local recurrence after partial gastrectomy for advanced gastric carcinoma. The Authors suggest that chemo and/or radiotherapy associated with surgical treatment can improve the prognosis in some patients with recurrence. Response to chemotherapy and time elapsing before recurrence appears may select this group of patients. PMID- 1436571 TI - [Peritonitis caused by jejunal perforation resulting from metastasis of pulmonary carcinoma]. AB - The Authors report a case of peritonitis due to perforation of a single small bowel metastasis in a woman affected by right upper lobar lung carcinoma still with neck's lymphnodes and cerebellar metastasis. They underline the rarity of the finding and analyze its clinical, therapeutic, prognostic problems. PMID- 1436572 TI - [Diverticulitis of the right colon. Presentation of a clinical case]. AB - The recent observation of one case of diverticulitis of the right colon led to an evaluation of clinical diagnostic and therapeutic aspects of this comparatively rare condition, on the basis of reported data. Preoperative diagnosis is very difficult because it clinically resembles acute appendicitis in many ways, or because of the objective observation of a mass in the right iliac fossa. Instrumental examinations require preparation times that are often incompatible with the degree of surgical urgency. In the reported case, the inflammatory process was modest and treatment was straightforward, there being no diagnostic doubts. This confirms the fact that in so-called "usual" cases, the idea surgical approach must be as conservative as possible. In so-called "hidden" cases, on the other hand, the doubt as to the nature of the pathology often leads to extensive surgery, such as right hemicolectomy. PMID- 1436573 TI - [Postoperative extrapleural pneumothorax. Presentation of a case]. AB - The authors discuss a case of pneumomediastinum observed in the course of acute bronchitis and after an operation performed with general anesthesia and orotracheal intubation. PMID- 1436574 TI - [Pseudocyst of the adrenal gland: diagnosis and treatment. Description of a clinical case]. AB - A case of pseudocyst of the suprarenal gland in a 32-years-old woman is reported. Stress is laid on the description of the clinical case and the diagnostic and therapeutic problems involved are reviewed. PMID- 1436575 TI - [A case of retroperitoneal leiomyosarcoma. Considerations]. AB - A case of retroperitoneal leiomyosarcoma is reported. The retroperitoneal localization is quite unusual and early diagnosis is really difficult. Only operation can offer any chance for cure of this neoplasm and radiotherapy and chemotherapy can be very useful. Tumor size and location are the major prognostic factors. PMID- 1436576 TI - [Primary malignant lymphoma of the parotid gland. Report of a case]. AB - Primary malignant lymphoma of the parotid gland is often correlated, in literature data, with inflammatory autoimmunological disease of the salivary gland. Finding of blasticlymphoid cells in myoepithelial scialoadenitic areas in a case of parotid disease is described by the Authors. Needle may be useful in detecting these high radio-chemosensitive neoplasms to reduce the occurrence of complications of total parotidectomy. PMID- 1436577 TI - [Choledocholithotomy and papillosphincterotomy in surgery of the bile ducts]. AB - The Authors argue about the different surgical choices feasible in case of CBD stones. They consider a case-record of 74 patients that underwent, from January 1988 to June 1990, choledocholithotomy or transduodenal sphincterotomy for non neoplastic pathology of the CBD in the I Divisione di Chirurgia Generale OO.RR. Bergamo. Analysis of the data shows a significant pre-operative alteration of the gamma-GT plasmatic levels. That represent a risk-index useful to suspect a silent CBD lithiasis. The good results attained with the choledocholithotomy and with the transduodenal sphincterotomy show the efficacy of both methods, that keep up different indications. The Authors point out the efficacy of the antibiotic prophylaxis in the prevention of the operative infections. PMID- 1436578 TI - [Reconstruction of the abdominal wall for "major" hernia. Conventional methods vs the use of prosthesis]. AB - The result of using traditional techniques in the treatment of large hernias of the abdominal wall (recurrent inguinal hernia and incisional hernia) are compared with those obtained by using prosthetic material. In most cases of incisional hernia the reconstruction was carried out by traditional techniques. Instead, the Authors' preference is for the use of prosthetic material in the treatment of recurrent inguinal hernia. PMID- 1436579 TI - [Local and regional recurrence of cancer of the breast]. AB - The Authors, through the study of their patients, and comparing it to other reports, help to further define the meaning, prognosis and type of treatment of local recurrences (LR) in breast cancer. They study 25 cases of LR after 238 operations on which regular clinical follow-up was carried out. They consider the various prognostic indicators for LR, the types of treatment and the results which are reached. Median survival after LR treatment was significantly better in patients N- (49 months vs 7 months in N+: p = 0.004). LR was more frequent when primary tumor was situated in inner quadrants; only 36% of their cases depend on primaries of the upper outer quadrant. An aggressive treatment (surgery, radiotherapy, chemotherapy) insures a better survival even if primary cancer is N+ greater than 3. The importance for prognosis of lymphnodal status is confirmed. Possible explanations are presented regarding the relatively lower incidence in upper outer quadrant cancers. An aggressive treatment of LR is suggested, specially when prognostic indicators are unfavourable: LR is very often a sign of systemic relapse of illness, particularly when it occurs after a short disease-free interval. PMID- 1436580 TI - [The use of Sorbsan in the treatment of the donor site of skin transplantations]. AB - Sorbsan is a new dressing composed of alginate fibers extracted from seaweed. It is claimed to have important hydrophilic, haemostatic and biocompatible qualities. Sorbsan was used in the treatment of the donor site of split skin grafts in 52 patients operated in this department from 1988 to 1990. The patients of this series required a skin graft for various reasons as detailed below: a) skin burns in 24 cases; 2) covering of a muscle flap used in the treatment of sacral pressure sores in 15 cases; c) 13 cases of loss of substance from other various causes. Healing time averaged 16.8-13.4 and 9.3 days respectively in the three groups reported above. In 85% of cases, healing was achieved in a period variable between one and two weeks and a half, varying in accordance with patient age and general conditions. The speed of healing, particularly where thin grafts were taken, allowed multiple split skin grafts to be taken from the same donor site, facilitating the treatment of extensive skin burns. The dressing can be removed with ease with only minimal discomfort to the patient. The incidence of side effects such as itching and scar hypertrophy or pigmentation is low. We haven't noticed any allergic reaction in this series. We found the use of this dressing satisfying in the treatment of donor sites of split skin grafts, particularly in terms of patient comfort and speed or healing. PMID- 1436581 TI - [The application of microanastomoses in the surgical treatment of varicocele]. AB - We operated on 50 patients with varicocele employing microsurgical anastomosis. Clinical results were satisfactory with varicocele disappearing 49 times out of 34 cases. The shunt between a high regimen pressure with a lower one improve the venous drainage of the testis. These new techniques must be selected according to the pathogenic mechanism of varicocele. PMID- 1436582 TI - [Progressive pneumoperitoneum in the preparation for surgical intervention for voluminous ventral hernias]. AB - The paper report three patients suffering from voluminous ventral hernias who were treated using progressive pneumoperitoneum as a preparative method prior to reparative surgery. On the basis of the results obtained, the authors sustain the rationality, safety and efficacy of the procedure, in particular given its ability to reestablish good respiratory and circulatory function in those cases where the latter were severely affected by hernia. Since this method needs a longer application time and therefore involves a greater economic burden, pneumoperitoneum should probably be reserved for selected cases, and alternative techniques should be used in patients where hernia is more easily resolved. PMID- 1436583 TI - [MTBE perfusion via nasobiliary drainage followed by endoscopic lithotripsy in cases of complicated lithiasis of the common bile duct]. AB - Pernasal catheter perfusion with MTBE and subsequent endoscopic lithotripsy is an effective treatment of complicated common bile duct lithiasis in which a first endoscopic attempt has failed. The authors analyzed their experience in 1990. PMID- 1436584 TI - [Merkel's tumor. Some comments and the authors' personal cases]. AB - The clinical features of 7 cases of primary neuroendocrine carcinoma of the skin (Merkel cell tumor) are reported. This cancer arises in the dermis and subcutaneous tissues of elderly individuals. Natural history is characterized by local recurrences (30%), regional lymph node metastases (65%) and distant metastases (40%). Surgery is the elective treatment, chemotherapy and radiotherapy resulted in only short-term palliative response. PMID- 1436585 TI - [Carotid-subclavian bypass. Our experience with locoregional anesthesia]. AB - Carotid-subclavian bypass has been adopted since 1956. The commonest indication is to abolish arterial occlusion or stenosis in patients with subclavian steal syndrome. Ten patients were submitted to carotid-subclavian bypass under regional anaesthesia: block of anterior rami of spinal nerves C3-C4 and block of cervico brachial plexus by injection into the continuous perineural connective tissue space at the level of C6. The surgical procedure required carotid occlusion and cerebral function monitoring. The advantages of regional anaesthesia are the ability to monitor the patient's cerebral perfusion and function, to detect intraoperative ischaemia and embolisation and minimal interference with the cardiovascular and respiratory function. PMID- 1436586 TI - [Acute diaphragmatic lesions due to closed thoracic-abdominal trauma]. AB - Diaphragmatic injuries due to blunt trauma are steadily related to a high mortality. Their diagnosis may be difficult, due to the lack of specific symptoms and, more frequently to the high incidence of coexisting lesions which can mask the clinical appearance. This work presents the main aspects of ten cases admitted to the Emergency Surgery Division of Cagliari (USL 21), during the last seven years, with a review of the literature. PMID- 1436587 TI - [Drainage of the pleural cavity]. AB - The authors, from their personal experience, demonstrate the goals, the indications, the techniques and complications of performing a drain of the pleural cavity (DCP). DCP has an important role as a single operation or at the end of every thoracic operation. For this reason it is mandatory to respect the principles and the concepts reported by the authors. PMID- 1436588 TI - ["The difficult nose". Notes on the surgical technic in selected cases of septorhinoplasty]. AB - The authors present a series of 20 patients who have undergone a complex septorhinoplasty. Its complexity is due to the presence of a serious deviation of the nasal septum, with an altered anatomy and position, and to the contemporaneous malformation of the nasal profile, laterally displaced in respect to the facial axis and with accentuated hump of the nasal bones. The aim of this presentation is to indicate the resolution of both problems with a single surgical operation. PMID- 1436589 TI - [The prevention of DVT after general surgical interventions for cancer pathology]. AB - The efficacy of postoperative DVT prophylaxis of defibrotide and heparin calcium was evaluated in a group of 47 patients undergoing general surgery for oncological pathologies. A sub-group (24 patients) received defibrotide treatment, 400 mg b.i.d. i.m.; the second subgroup (23 patients) was treated with heparin calcium, 5000 IU b.i.d. s.c., from the day before operation until the 7th postoperative day. No postoperative thrombotic symptoms were observed in either group of patients. PMID- 1436590 TI - [Atypical metastases from gastric carcinoma. A primary and isolated case localized in the abdominal wall]. AB - The authors report a rare case of gastric carcinoma metastasis localised in the anterior abdominal wall which was an isolated and primary sign of disease. After having underlined the rarity of the case, there is a brief discussion of aspects related to the spread of primary tumours in relation to other cases reported over the past decade; the most important reports of atypical secondary localisations are listed. PMID- 1436591 TI - [A case of ileal perforation due to a leiomyoma]. PMID- 1436592 TI - [A rare tumor: desmoid of the musculus rectus abdominis. Apropos a clinical case]. AB - The authors report a case of left abdominal rectum muscle desmoid tumor which has been surgically treated. After some considerations of the particular pathogenetic, anatomopathological and clinical characteristics of this neoplasm, they state that a precise preoperative diagnosis is always difficult, in spite of modern diagnostic means. They conclude that, nowadays, surgical extirpation is the most reliable therapeutical method, although it is burdened by a consistent incidence of local recidives (over 30%). PMID- 1436593 TI - [Extraskeletal myxoid chondrosarcoma of the abdominal wall. A clinical, histological, ultrastructural and cytofluorimetric case study]. AB - The authors present a case of extraskeletal myxoid chondrosarcoma of the abdominal wall, an unusual localization and specific presentation. According to the literature, the clinical characters of this kind of tumor, the diagnostic iter and the therapeutic indications are being examined. The actual anatomopathological patterns used for the diagnosis of this neoplasm are being underlined. PMID- 1436594 TI - [A strangulated obturator hernia. Comments on 2 cases]. PMID- 1436595 TI - [A case of transareolar mastocele (tuberous breast) following an early lateral thoracotomy]. AB - The paper reports a rare case of breast anomaly, classified as "tuberous breast", which was of a specific nature since it was the result of a lateral thoracotomy performed at the age of 7 days old to esophageal atresia. The paper analyses the possible etiopathogenetic mechanisms. The use of an original reparative technique enable an adequately shaped and protruding breast to be obtained without the use of prosthesis and without leaving additional scars. PMID- 1436596 TI - [Angioma of a finger: the usefulness of a graft from the hypothenar eminence for covering the defect]. AB - Skin grafting remains the simplest option when bone is not exposed in soft tissue losses of the digits of the hand. As opposed to traditional donor sites, a split thickness skin graft from the hypothenar eminence provides specialized skin similar to the one to be replaced. The graft remains elastic and soft in follow up, without hyperpigmentation, hyperkeratosis, fissuring and hypertrophic scarring at the margins. As well as in acute trauma situations, the use of split thickness skin grafting from the hypothenar eminence can also be extended to resurfacing defects in elective hand surgery. As an example, we describe a case of an ulcerated capillary hemangioma on the dorsal surface of the fifth digit at the distal interphalangeal joint. PMID- 1436597 TI - [Transcutaneous oximetry in symptomatic diabetics]. AB - In a group of 33 patients affected by diabetes mellitus transcutaneous oxygen tension (PtcO2) was measured by means of a Clark polarographic electrode. Patients were divided into 3 groups according to the symptoms and/or to the clinical findings: group A: paresthesia (22 limbs); group B: claudication (6 limbs); group C: rest pain and/or necrosis (13 limbs). Moreover, group C was divided into: C1 trophic neuropathy lesion (7 limbs) and C2 trophic ischemic lesion (6 limbs). Our data point out that there is a statistically significant difference between mean PtcO2 values in limbs with trophic ischemic lesions versus the other 3 groups. Therefore, PtcO2 is particularly indicated and useful in the study of diabetic patients with peripheral vascular disease where integrates the other instrumental noninvasive techniques. PMID- 1436598 TI - [Nutrients, anthropometric characteristics and osteoporosis in women in the recent and late postmenopausal period]. AB - Bone mineral content (BMC) at two different radial sites (mid-diaphysis and ultra distal epiphysis), anthropometric measurements (Body Mass Index, Lipidic Area, and Muscular Area) and nutrients intake were measured in two populations of women selected on the basis of early (< 9 years) or remote (> 15 years) menopause. The results show the presence of positive relationships between BMC, and protein and lipid intakes in the population of women in early menopause; in the other population no relationships were found. Glucid, fibre and calcium intakes were not related to the BMC of both populations. The positive relationships between BMC, and protein and lipid intakes in the population of women in early menopause is likely mediated by anthropometric characteristics as Body Mass Index and Muscular Area. PMID- 1436599 TI - [Zymogenic cell mass and serum pepsinogen I: the cell secretory correlations in patients with gastric intestinal-type cancer of the corpus-fundus]. AB - The chief cell mass and serum pepsinogen I (PGI) have been evaluated in 18 patients with gastric cancer of intestinal type of the body-fundus. Moreover, a correlation with the parietal cell mass and the maximal acid output it has been effected. The patients have been subdivided in relation to histologic condition of the fundic mucosa. In case of gastric cancer with preatrophic fundic gastritis it has been revealed hypozymogenism with normoPGI and hypoparietalism with hypochlorhydria, in case of gastric cancer with atrophic fundic gastritis it has been revealed hypozymogenism with hypoPGI and hypoparietalism with hypochlorhydria. From this experience it emerges a similar anatomic-functional profile between gastric cancer of the body-fundus and chronic fundic gastritis without cancer. In particular, it emerges that serum PGI is a good marker of atrophic fundic gastritis, but it is not discriminant between atrophic fundic gastritis and atrophic fundic gastritis associated to gastric cancer. PMID- 1436600 TI - [Transient cerebral ischemia and the risk factors]. AB - A retrospective study was carried out in a general medicine ward of 100 male patients suffering from their first transient ischemic attack (TIA) in order to evaluate the incidence of different cerebrovascular risk factors. The results were then compared with those from another group of 100 patients suffering from initial cerebral ischemic softening (CIS) in order to identify a cerebrovascular risk population taking into account clinical similarities and common and divergent features. The study revealed that age is the prime risk factor in the genesis of TIA, followed by arterial hypertension and hypercholesterolemia. From a comparison with the group of patients affected by initial CIS it was clear that TIA is typical of senility and is more closer correlated to age than other risk factors; therefore, che TIA population is an expression of those who have "survived" cerebrovascular death due to the lesser exposure to risk factors. PMID- 1436601 TI - [Ticlopidine and platelet function]. AB - In macular degeneration disease of the eye, we have studied the behaviour of vitro thrombocyte aggregation/deaggregation and ex vivo plasma beta thromboglobulin level (Born aggregometer, RIA kit) during administration of an antiaggregant platelet drug (ticlopidine). We have observed the presence of a prothrombotic state that improves after 15 days of administration of drug. In fact platelet aggregation and beta-thromboglobulin level significantly decrease while thrombocyte deaggregation significantly increase. The correlations between deaggregation, aggregation and beta-thromboglobulin level suggest that the antiaggregant action of the ticlopidine is linked to the inhibition of platelet release reaction. PMID- 1436602 TI - [The possible effects of galactosaminoglucuronoglycan sulfate on blood coagulation processes]. AB - Ten patients with osteoarthritis were treated in an open study with galactosaminoglucuronoglycan sulphate for 60 days (800 mg b.i.d. per os). The following haemostatic indices were measured before and after treatment: platelet count, adhesion and aggregation; prothrombin time and activity; partial thromboplastin time and antithrombin III. Total and HDL cholesterolemia, triglycerides, arterial pressure and heart rate were also measured. No blood coagulation index was found to be significantly altered in treated patients. In addition, neither variations from the normal limits of lipidemic and cardiocirculatory values nor adverse effects related to treatment were reported. Although the study was carried out in a limited population, these findings show that GGG does not interfere with the coagulation process and, from a more general point of view, they confirm its excellent tolerance. PMID- 1436603 TI - [Heparan sulfate: its kinetic effects on fibrinolytic-coagulative parameters after oral administration]. AB - The effects of the oral administration of 100 or 200 mg of heparan sulphate or placebo over time were assessed in nine healthy volunteers. Blood samples were collected at 1, 2, 4, 6, 8 and 12 hours after administration to assay prothrombin activity, partially activated thromboplastin time, and the activation to tPA and PAI-1. A significant increase (P < 0.001) of tPA activity and a reduced inhibition of fibrinolytic systems by PAI-1 were observed. These effects, which were clearly dose-dependent, appeared 2 hours after administration and persisted for 6-8 hours. On the contrary, no changes were recorded in coagulative tests at the doses used. PMID- 1436604 TI - [Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study]. AB - This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability. PMID- 1436606 TI - [Why a gynecological consultation service in a hematology day hospital. Our experience]. AB - The paper described the role of a gynaecological advisory service in an hematological day hospital. The main gynaecological problems which arose during anti-cancer and immunosuppressive therapy were classified according to patients' symptoms. The paper stresses the need for close collaboration between hematologists and gynaecologists and underlines the psychological importance of this aspect from the patient's point of view. PMID- 1436605 TI - [The use of thymopentin in preventing acute infectious relapses in elderly subjects with COPD]. AB - In this study the authors considered the effectiveness of thymus hormone in the prevention of acute infections within a group of elderly subjects affected by COPD. Ten subjects were considered, nine males and one female in the age included between 65 and 89 years (medium age = 70.2 +/- 6.96 years), with clinical evaluation and altered functional respiratory tests (FEV1 < 70%). The patients were treated with timopentina 50 mg s c three times a week for a month. The following parameters were considered: leucocytes/mm3; lymphocytes/mm3 in standard conditions, in the first and in the second month after the therapy start, contagious episodes two months before and two months after the beginning of therapy. The Authors noticed a real reduction in the relapses of the infectious episodes (11 relapses in the months before therapy and 2 relapses after therapy had begun). Leucocytes/mm3 rates were reduced (8.070 +/- 3.414 in standard conditions, 6.420 +/- 1.041 after 60 days; 0.2 < P < 0.1). Lymphocytes/mm3 rates were increased, 1.579 +/- 752 in standard conditions, 2103 +/- 491 after 60 days 0.2 < P < 0.1). These preliminary data seem to show in the small number of cases considered, the effectiveness of the thymus hormone (thymopentina) in elderly subjects affected by COPD. PMID- 1436607 TI - [Physician immunity and privileges during the Roman Empire]. PMID- 1436608 TI - [Systemic mastocytosis with portal hypertension and hepatocellular failure]. AB - Systemic mastocytosis is a rare disease of mast cell proliferation with cutaneous and multi-visceral involvement. Portal hypertension and ascites are rare manifestations of systemic mastocytosis. We report a case of systemic mastocytosis presenting with extensive nodular cutaneous lesions and hepatic dysfunction, manifested by portal hypertension (ascites, splenomegaly) and derangement of metabolic function (hyperammonemia, hypoalbuminemia, hypocholesterolemia), a picture resembling that of a common cirrhotic form. The correct diagnosis was established only after tissue sections were appropriately stained for mast cells. On the basis of our and other observations we suggest that systemic mastocytosis be added to the list of infiltrative diseases of the liver with potential evolution to portal hypertension and compromise of biochemical functions. PMID- 1436609 TI - [Ischemic colitis manifested as Crohn's disease. A case report]. AB - Ischaemic colitis has many and different clinical features as it is often linked to the severity of ischaemic injury. In this paper two patients with clinical features of Crohn's disease are reported. In both patients the diagnosis has been confirmed with endoscopy and biopsy. They have been treated with specific therapy until they developed bowel obstruction in one case and peritonitis in the other. Both patients underwent laparotomy and the histological specimen showed a picture of ischaemic colitis. In one case a Dixon's resection was done, in the other Hartmann's operation. PMID- 1436610 TI - [The infusion of high-dose immunoglobulins in a case of idiopathic thrombocytopenic purpura]. AB - Idiopathic thrombocytopenic purpura (ITP) is a disease characterized by the presence of circulating antiplatelet antibodies, which can cause platelet destruction, through the mediation of the reticuloendothelial system (RES). We report on a patient affected with ITP insensible to first line steroid therapy, who achieved a complete response following the administration of high-dose immunoglobulins (HDIgG, 400 mg/kg/die for 5 days), in association with decreasing doses of steroids. At the end of the treatment with immunoglobulins, the patient presented a normal platelet count and, up to date, 5 moths from the end of therapy, he is in good shape and presents normal platelets values. PMID- 1436611 TI - [Unilateral gynecomastia induced by the use of anabolic steroids. A clinical case report]. AB - The authors studied a case of left unilateral gynecomastia occurring in a 26-year old body-builder after anabolic steroids assumption. The mammal features were found by echography and mammography and they showed the presence of a 3 cm diameter retroareolar area of gland tissue surrounded by fibrotic tissue. After excluding every likely cause giving gynecomastia through laboratory tests, it was clear a relationship with the assumption of high doses of anabolic hormones, with particular regard to methyltestosterone. Therefore, also this substance which on its own is not aromatized by extrasplanchnic tissues, can be responsible for man's mammal hypertrophy, if joined to a slight iatrogenic liver cytolysis. PMID- 1436612 TI - [Non-sexual transmission of sexually transmissible diseases]. AB - Sexually transmitted diseases can be transmitted through nonsexual transmission. Neonatal contamination has been proven at parturition from mothers with anogenital diseases. Another example is transmission through exchange of underwear, towels, bed sharing, etc. It is possible that contamination may occur with use of the contaminated speculum and forceps. Use of laser may release viruses during treatment for viral diseases. Candidiasis, trichomoniasis and genitalis condilomatosis, which should not be considered an exclusively sexually transmitted diseases are considered. PMID- 1436613 TI - [Synchronous associations of tumors in the pelvic organs of the female genital tract]. AB - The Authors report their findings concerning the synchronous associations of tumours involving pelvic organs in the female genital tract observed at the Gynecological Clinic, Aquila. From January 1980 to December 1991, 9 cases (4.28%) of synchronous tumours were found in a total of 210 cases of womb, ovary and vagina tumours. The paper examines the clinical problems and questions of anatomopathological characterisation raised by these associations. PMID- 1436614 TI - [Clinical evaluation of an immunological test for premature rupture of the fetal membranes (ROM check test)]. AB - Commonly used methods for detecting amniotic fluid in the vagina include research LA cells, ferning, nitrazina paper, ultrasound and dye injection. These methods are difficult to interpret or invasive. We have tested a new method which detects a fetal isoform of fibronectin in vaginal secretion when amniotic fluid is present. Clinical trials demonstrate the sufficient reliability in detecting amniotic fluid in the vagina of women with rupture of amniotic membranes. PMID- 1436615 TI - [Collagenase IV and laminin receptors in cultured trophoblast cells]. AB - Human trophoblast cells were obtained from a term placenta and cultured through several stages. Using specific antibodies marked using an avidin biotin system and given the characteristic "invasiveness" of placental tissue, the Authors investigated the possible presence of those markers which have been found to be correlated with invasive and metastatic tumour cells. The positivity shown by cultured trophoblast cells towards laminin receptors and collagenase IV may have important implications which might explain the strange formation and maintenance of the human uteroplacental circulation in which embryonal tissue is in direct contact with maternal blood. PMID- 1436616 TI - [Hysteroscopy in the early diagnosis of endometrial neoplasia. Personal experience with 200 consecutive cases]. PMID- 1436617 TI - [Hysteroscopy as a diagnostic method in postmenopausal metrorrhagia]. AB - We performed 215 hysteroscopies for post-menopausal bleeding. The most common abnormalities found were endometrial hypoatrophy and low-risk hyperplasia, the less common high-risk hyperplasia and adenocarcinoma of the endometrium. The correlation between hysteroscopic view and endometrial sampling was always very high. Hysteroscopy seems to be a very accurate method for evaluating patients with post-menopausal bleeding especially if associated with endometrial sampling. PMID- 1436618 TI - [Radiologic types in mammography in the 90-s. New classification]. AB - The Authors present a critical review of the classification of radiological types in mammography proposed in 1986. On the basis of their personal experience over the past years, and in the light of the changed indications given by screening the asymptomatic population, a series of 6,072 mammographies performed over a 12 month period were included in the study. These were non-selected cases undergoing X-ray examination for a variety of reasons, ranging from periodical control to carcinophobia. No clinical or epidemiological data were taken into account in order to limit analysis to radiological factors alone. The analysis of results allows a few comments to be made and suggests an interpretation which differs from that in vogue in the 80s. First of all, the steady rise in mammographic controls calls for an uniformity of technique with interchanges of information between the various centres of breast cancer in order to encourage increasingly accurate diagnostic evaluations. The higher incidence of the trabecular type (33.7%), typical of women in their 40s, underlines the greater diffusion of mammography which now starts at an increasingly early age. Current control programmes (in spite of some recent controversy) include 40-year-old women who undergo basic mammography in spite of the absence of symptoms. On the other hand, the irreplaceable diagnostic value of mammography during the asymptomatic years is now widely recognised, even in those women who undergo a regular clinical examination. The fibroadipose type has dropped to second place (26.8%) not due to a reduction in the number of these cases, but rather on account of the lower age at which women first undergo mammography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436619 TI - [Sampling devices for the Papanicolaou test]. AB - Smear quality is related to the experience of the sample taker and also to the screening instrument used. Most Authors concur that both an endocervical and an ectocervical specimen must be collected to assure adequate sampling of the transitional zone. The cytobrush alone is effective mainly for endocervical sampling while the Ayre spatula alone is effective mainly for ectocervical sampling; the cotton swab is ineffective for both endocervical and ectocervical sampling. Values and failure of the sampling devices are described. PMID- 1436620 TI - [Trends in our approach to the therapy of urinary stress incontinence]. PMID- 1436621 TI - [Experience with ceftriaxone in the antimicrobial chemoprophylaxis in obstetric gynecologic surgery]. PMID- 1436622 TI - [Obstetric-gynecologic problems in the developing countries]. AB - The integrated health programmes in the developing countries give priority to the improvement of women's living conditions and of maternal and child health medical attention. The Authors, as specialists in Obstetrics and Gynecology active in an African country, present the most frequent pathological situations which, in their experience, can lead to the death of the pregnant woman. The social reality of the underdeveloped world and the high Total Fertility rates, due partly to the absence of a contraceptive culture, too often see the woman of reproductive age threatened by the complication deriving from abortion, ectopic pregnancy and labour. The obstetrician needs to know how to solve these emergencies and how to train the local personnel in order to guarantee as much as he can the essential obstetrical functions. PMID- 1436623 TI - [Cervico-vaginal screening in some Local Sanitary Units of the Emilia-Romagna region]. AB - Some Local Sanitary Units (USL) of the Emilia-Romagna region were contacted to define cervical screening variables, such as adequacy of smear technique, data collection and evaluation, laboratory quality control modalities of invitations to screening. Our data show there are a lot of deficiencies in the present management of the cervical program in Romagna. The most serious inadequacies concern data evaluation, follow-up, cytologic quality control, modalities of active invitations of women to screening. The survey has confirmed the need for launching organized programs of cervical screening to promote their efficacy of diagnosis and therapy. PMID- 1436624 TI - [Brenner tumor of the ovary. Report of a case in a pregnant women]. AB - The Authors, after a short review on the histopathological, histogenetic and prognostic aspects, report a clinical case observed by them, in a pregnant woman. They emphasize the asymptomatic obstetric course and the accidental discovery during surgical treatment. PMID- 1436625 TI - Murine BC1 RNA in dendritic fields of the retinal inner plexiform layer. AB - Rodent BC1 RNA is a non-messenger RNA polymerase III transcript that is almost exclusively expressed in nerve cells. BC1 RNA has been localised in somatic and dendritic domains of neurons, and its location has been interpreted to indicate a functional role in extrasomatic postsynaptic protein synthesis. In previous in situ hybridisation experiments, it has been demonstrated that in the retina most of the BC1 labelling signal was confined to the ganglion cell layer and the inner plexiform layer. Dendritic processes of several types of neurons form the neuritic plexus of the inner plexiform layer, and in order to determine the contribution of ganglion cells to the BC1 labelling signal, we eliminated this cell type by transecting the optic nerve unilaterally in newborn mice. Deletion of the ganglion cells resulted in a significant reduction although not a complete elimination of the BC1 signal in the inner plexiform layer. These data indicate that dendritic processes of both ganglion cells and amacrine cells contain BC1 RNA. PMID- 1436626 TI - Histological study on ouabain immunoreactivities in the mammalian hypothalamus. AB - The endogenous digitalis-like factor (EDLF) which has recently been purified from human plasma and identified as 'ouabain', a cis-trans-cis steroid of plant origin, is thought to be similar to the hypothetical humoral factor, 'endogenous digitalis-like substance (EDLS)'. In order to examine the hypothesis that EDLS is produced in the hypothalamus, we prepared an ouabain-specific antibody, and applied it to rat and macaque brains. Ouabain immunoreactivities were observed in the hypothalamus of both species. The immunopositive neurons were distributed in paraventricular and supraoptic nuclei, and some other hypothalamic regions. Their nerve fibers were seen abundantly in the hypothalamo-neurohypophysial regions. These results strongly support the possibility of existence of cis-trans-cis steroid including EDLF in mammalian brain. PMID- 1436627 TI - Inhibitory effects of endothelin-3 on vasopressin release from rat supraoptic nucleus in vitro. AB - Endothelin (ET) is thought to be involved in the central regulation of body water metabolism. A recent perfusion study of rat hypothalamus showed that ET has a direct stimulatory action on arginine-vasopressin (AVP) release. This study was undertaken to investigate whether ET acts directly on AVP release for supraoptic nucleus (SON) neurons, using brain slices containing only the SON. It was demonstrated that ET inhibited the AVP release dose-dependently from 10(-11) M to 10(-6) M. No difference of the effects of ET-1 and ET-3 on AVP release was observed. These results suggest that ET directly inhibits SON neurons through the ETB receptor. PMID- 1436628 TI - Y-29794--a non-peptide prolyl endopeptidase inhibitor that can penetrate into the brain. AB - A novel non-peptide prolyl endopeptidase (PPCE) inhibitor, Y-29794, has been identified. Y-29794 selectively and competitively inhibited rat brain PPCE (Ki = 0.95 nM) in a reversible manner. Ex vivo study demonstrated that Y-29794 could penetrate into brain to exhibit dose-dependent and long-lasting inhibition. Furthermore, Y-29794 was found to potentiate the effect of TRH on the release of ACh in the rat hippocampus. These results indicate that Y-29794 is an orally active, potent and specific PPCE inhibitor and should be of value in studies on the physiological role of the enzyme in neuropeptide metabolism especially in memory process. PMID- 1436629 TI - Protective effect of NGF atelocollagen mini-pellet on the hippocampal delayed neuronal death in gerbils. AB - Very recently, contradictory results were presented as to the effects of exogenous nerve growth factor (NGF) on the hippocampal delayed neuronal necrosis following transient ischemia. In the present study, we administered a large amount of NGF with the atelocollagen mini-pellet system, measured the local NGF contents, and evaluated the effect of this neurotrophic factor on the postischemic hippocampal pyramidal cells in gerbils. We concluded that the exogenous NGF, when given continuously at sufficient concentrations, prevents pyramidal cell damage. The possible cause of discrepancy in previous studies is discussed. PMID- 1436630 TI - Time-dependent effects of oral morphine on autotomy following brachial nerve section in the rat. AB - In this study, the effects of morphine in drinking water on autotomy in male F344 rats having undergone brachial nerve sections were assessed during a 3-week period. Morphine was self-administered orally in tap water by the rats. Rats administered morphine just after the nerve section or 1 week after the nerve section showed a significant increase in the severity of autotomy when compared to the rats administered distilled water. Morphine had no effect on autotomy when it was administered 2 weeks after the nerve section. These results suggested that the effect of oral morphine on autotomy changes in a time-dependent manner. PMID- 1436631 TI - Vasodilator flare due to activation of superficial cutaneous afferents in humans: heat-sensitive versus histamine-sensitive fibers. AB - Histamine-sensitive nerve endings are assumed to terminate in the superficial epidermis. Heat-sensitive nociceptors that are excited by brief carbondioxide laser pulses must also terminate within the epidermis, because this infrared radiation has an extinction length of about 10 microns. We now compared laser heat stimuli (10 W, 50 ms, 20 mm2) with intradermal injections of histamine (10( 10) to 10(-8) mol) in their capacity to cause cutaneous vasodilatation (flare) in awake human subjects. Cutaneous blood flow was measured with a two-channel laser Doppler device. The radiant heat pulses caused a transient cutaneous vasodilatation that spread at least 15 mm from the stimulus site. There was no visible flare and vasodilatation could only be detected by laser Doppler measurements. Although the heat pulses elicited enough nociceptor activity to be perceived as moderately painful, the magnitude of the vasodilatation was smaller and its duration shorter than after the smallest dose of histamine. In contrast, nociceptor activation by heat is usually stronger than by histamine. These data indicate that flare and pain are two different aspects of cutaneous small fiber function. PMID- 1436632 TI - Spontaneous hemorrhage in the cerebral cortex of immature rats. AB - We report the presence of spontaneous hemorrhages in the brain of normal neonatal rats. The quantitative evaluation showed that the hemorrhaging was most frequent in 4- to 5-day-old rats. Nearly all the lesions were found in the cerebral cortex of the lateral part of the forebrain hemisphere, particularly in the middle cortical layers. Their average incidence amounted to 6.71 +/- 2.95 per six 5 microns sections from 5-day-old rats. The lesions were nearly absent in the newborn and 7-day-old animals. We suggest that vascular wall immaturity and some extravascular factors, like developmental increase of blood pressure, may account for the perinatal hemorrhaging. PMID- 1436633 TI - Partial protective effect of MK-801 on MPTP-induced reduction of striatal dopamine in mice. AB - The protective effect of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced reduction of striatal dopamine (DA) was examined in C57 BL/6 mice. Striatal DA levels were significantly higher in animals receiving parenteral MK-801 before and for 48 h following MPTP administration after 28 days than in animals receiving MPTP alone. The effect was not due to inhibition of monoamine oxidase-B (MAO-B) by MK-801. These data suggest that NMDA receptors may be involved in some of the neurotoxicity produced by MPTP. PMID- 1436634 TI - Nilvadipine as a neuroprotective calcium entry blocker in a rat model of global cerebral ischemia. A comparative study with nicardipine hydrochloride. AB - The effects of two dihydropyridine type calcium entry blockers, nilvadipine and nicardipine hydrochloride (nicardipine), on the liberation of free fatty acids (FFAs) were investigated using an experimental model of global cerebral ischemia in rats, and were compared with their pharmacokinetic properties. Nilvadipine, but not nicardipine, at a dose of 100 micrograms/kg i.v., significantly attenuated the liberation of FFAs, particularly docosahexaenoic and arachidonic acid. Furthermore, the brain concentration of nilvadipine was higher than that of nicardipine after equivalent dosing. The results of the present study demonstrate that pharmacokinetic differences between these two calcium entry blockers might explain the difference in their pharmacological efficacy. PMID- 1436635 TI - Neurochemical lesioning in the rat brain with iontophoretic injection of the 1 methyl-4-phenylpyridinium ion (MPP+). AB - Iontophoretic injections of the 1-methyl-4-phenylpyridinium ion (MPP+) were made in the dopaminergic part of the substantia nigra to see whether this injection technique could be used for inducing localized neurochemical lesions in dopaminergic cell groups and to assess the effects of MPP+ on non-dopaminergic neurons. Three days after the iontophoretic injection of MPP+, a gliosis or necrotic hole was found in the dopaminergic and non-dopaminergic target areas. This effect depended on the injection parameters that were used; iontophoretic injections of short duration (less than or equal to 3 minutes) and low current strength (1.5 microA) caused the gliosis, higher injection parameters gave lesions. The estimated injected amount of MPP+ was between 0.5 and 10.8 nmol. Control injections, with sodium iodide, sodium chloride or N-methylpyridinium iodide showed that the neurodegeneration is not a side-effect of the iontophoretic injection procedure. It is concluded that iontophoretically injected MPP+ is toxic for all neurons, irrespective of the neurotransmitter used, and also for glia cells and fibers of passage. Excessive formation of free radicals, causing induction of lipid peroxidation, may be involved in the neurodegenerative process observed. PMID- 1436636 TI - Lack of evidence for coupling of the dopamine D2 receptor to an adenosine triphosphate-sensitive potassium (ATP-K+) channel in dopaminergic neurones of the rat substantia nigra. AB - Whole-cell patch clamp recordings were made from neurones in slices of rat substantia nigra zona compacta. The majority exhibited electrophysiological characteristics seen previously with intracellular recordings and were hyperpolarised by dopamine in a sulpiride-reversible manner. The sulphonylureas, tolbutamide and glibenclamide, did not reverse the response to dopamine and had no effect when applied alone. The potassium channel opener, cromakalim, was also without effect on dopaminergic neurones. Under our recording conditions, the potassium conductance activated by dopamine acting through the D2 receptor does not show the pharmacological characteristics of an ATP-sensitive potassium conductance. PMID- 1436637 TI - Reinnervation of denervated extensor digitorum longus of the rat by the nerve of the soleus does not induce the type I myosin synthesis directly but through a sequential transition of type II myosin isoforms. AB - The fast-contracting extensor digitorum longus (EDL) muscle of 1-month-old rats was denervated and reinnervated by the nerve innervating the slow-contracting soleus muscle. After variable periods of time, the myosin isoform content of the EDL was analyzed by sensitive electrophoretic techniques, which allowed to discriminate between the slow-type I and the three, IIA, (IID or IIX) and IIB, fast-type II myosin isoforms. Compared to the control EDL, which contains predominantly the IIB isoform, the operated muscles contained variable proportions of all the isoforms. Analysis of the results leads us to conclude that reinnervation of EDL induces a sequential transition of myosin isoforms: IIB ---(IID or IIX)----IIA----I. PMID- 1436638 TI - Effects of exogenous GM1 ganglioside on LTP in rat hippocampal slices perfused with different concentrations of calcium. AB - Combined actions of GM1 ganglioside molecules and Ca2+ ions on long-term potentiation (LTP) of the hippocampal CA1 synapses were examined in slice preparations. Application of exogenous GM1 ganglioside significantly enhanced LTP. Antigenic blocking of endogenous GM1 ganglioside by applying anti-GM1 antiserum appeared to attenuate LTP. Exogenous GM1 treatment not only antagonized LTP suppression caused by low Ca2+ (1.0 microM) in the perfusion medium, but also amplified LTP at high Ca2+ (5.0 microM) condition. Thus, GM1 may stabilize intracellular calcium levels to enhance synaptic potentiation. PMID- 1436639 TI - Dual capsaicin-sensitive afferent pathways mediate inhibition of gastric emptying in rat induced by intestinal carbohydrate. AB - The role of the vagal and spinal afferent innervation in the inhibition of gastric emptying induced by duodenal perfusion with a disaccharide (maltose 300 mM) was investigated in awake rats fitted with gastric and duodenal cannulas. Perfusion of the duodenum with maltose inhibited gastric emptying by 44%. Maltose induced inhibition of gastric emptying was reversed by 46% and 100% by functional ablation of the vagal or spinal capsaicin-sensitive afferent innervation, respectively. Pretreatment with the specific CCK 'A' receptor antagonist, MK329, completely abolished the effects of maltose on gastric emptying. These results suggest that disaccharides inhibit gastric emptying via activation of capsaicin sensitive afferents in the duodenal mucosa via a mechanism involving an action of CCK at type 'A' receptors, possibly located on afferent fibers. PMID- 1436640 TI - Tris inhibits (+)-[3H]SKF-10,047 binding to sigma receptors. AB - Tris-HCl is the most commonly used buffer in studies of radioligand binding to sigma receptors, with concentrations as high as 50 or 100 mM often used. We report here that these concentrations of Tris substantially inhibit (+)-[3H]SKF 10,047 binding to sigma receptors. The well-established inhibitory effect of Tris HCl on ligand binding to PCP receptors did not contribute to the presently reported inhibition of (+)-[3H]SKF-10,047 binding. The IC50 of Tris, determined in the presence of 10 mM potassium phosphate buffer, was 15.4 +/- 1.2 mM (n = 3, pH 8.0, 25 degrees C, 1 nM radioligand). Equilibrium saturation studies revealed an apparent competitive inhibition of binding. PMID- 1436641 TI - Methionine enkephalin accumulates in plasma but not in brain or cerebrospinal fluid of rats with acute toxic hepatitis. AB - In order to determine whether acute toxic hepatitis in the rat is associated with an accumulation of methionine enkephalin in plasma and increased blood-to-brain transfer of methionine enkephalin, immunoreactive methionine enkephalin levels were determined by radioimmunoassay in plasma, cerebrospinal fluid and whole brain samples from rats with thioacetamide induced acute toxic hepatitis. Thioacetamide treatment was associated with an 8.7-fold increase in plasma immunoreactive methionine enkephalin levels (P less than or equal to 0.005) 24 h after treatment. However, this marked elevation in plasma immunoreactive methionine enkephalin levels was not associated with an increase in whole brain or cerebrospinal fluid immunoreactive methionine enkephalin levels. These data suggest that increased plasma-to-brain transfer of methionine enkephalin does not occur in this model of acute toxic hepatitis. PMID- 1436642 TI - The A2-selective adenosine analog, CGS 21680, depresses locomotor activity but does not block amygdala kindled seizures in rats. AB - The actions of the highly selective A2 adenosine agonist, CGS 21680, in modulating kindled seizures and locomotor activity were examined. I.c.v. injections of CGS 21680 into the lateral cerebral ventricle in fully kindled rats were found to prolong the period of postictal EEG depression and reduce postictal spiking in a dose-dependent manner, while not affecting the behavioral seizure stage or afterdischarge duration. CGS 21680 injections also lead to a dose related inhibition of locomotor activity in rats exposed to an open field apparatus compared to rats receiving control injections of saline. These observations implicate the involvement of the A2 adenosine receptor in postictal phenomena and the locomotor depressant actions of adenosine, but do not indicate a direct anticonvulsant activity following A2 activation. PMID- 1436643 TI - Intracortical grafts of purified astrocytes ameliorate memory deficits in rat induced by chronic treatment with ethanol. AB - Chronic intake of ethanol in rat results in a substantial and permanent impairment in memory function which can be ameliorated by intracortical grafting of fetal tissue derived from the primordial basal forebrain. The present study demonstrates that grafting of purified astrocytes is equally effective in improving the performance in the eight-arm radial maze. In comparison, the rate of behavioral recovery is even more accelerated after grafting of astrocytes than after fetal basal forebrain transplants. The improvement in memory function can be detected as early as 2 weeks after operation and is accompanied by an increase in the activity of choline acetyltransferase in the basal forebrain previously reduced after ethanol treatment. Graft-induced behavioral recovery in the present paradigm is most likely due to a neurotrophic influence of astrocytes mediated via the cholinergic basal forebrain system. PMID- 1436644 TI - Unilateral hippocampal lesions prevent recall of a passive avoidance task in day old chicks. AB - The role of the hippocampal system in learning and memory processes in the chick was investigated. A series of experiments examined the effects of lesions in the hippocampal system on the acquisition and retention of a passive avoidance task. Chicks given pretraining bilateral hippocampal lesions showed a decrease of retention of the avoidance response evaluated 3 h posttraining. When given unilaterally, left, but not right lesions, resulted in reduced avoidance. However, bilateral posttraining lesions, made 1 h after training, did not interfere with retention of the task. These results suggest an involvement of the hippocampal system in learning processes in the chick. PMID- 1436645 TI - Differences in the axon composition of nerves supplying the rat knee joint following intra-articular injection of capsaicin. AB - This study was used to examine the ultrastructure of articular nerves supplying the medial aspect of the rat knee joint following injection of capsaicin into the synovial cavity. One week after the intra-articular injection of 0.2 ml of 1% capsaicin solution there was significant reduction in the number of unmyelinated fibres. Two weeks post-injection this appeared to recover and by 4 weeks post injection no further changes were observed. Myelinated fibres were unaffected by capsaicin injection. This procedure provides an effective means of producing short-term degeneration of unmyelinated fibres innervating the knee joint. PMID- 1436646 TI - Development of long-term potentiation in the somatosensory cortex of rats of different ages. AB - The age dependence of possible long-term potentiation (LTP) induction in rat somatosensory cortex was studied in in vitro slice experiments. Coronal slices were prepared from the somatosensory cortex of rats of different ages, and excitatory postsynaptic potentials evoked by stimulation of the white matter (0.1 Hz, subthreshold for spike) were recorded intracellularly. In 70% of the slices taken from 2-week-old rats, a moderate potentiation (20-30%) could be induced by either 5 or 100 Hz stimulation. No LTP was observed in younger (1 week) or older (3 weeks) cortex. On the basis of our experiments an important ontogenetic role of increased synaptic efficacy is suggested in a critical developmental period of rats after birth. PMID- 1436647 TI - The excitation site of the trigeminal nerve to transcranial magnetic stimulation varies and lies proximal or distal to the foramen ovale: an intraoperative electrophysiological study in man. AB - The excitation site of the trigeminal nerve using transcranial magnetic stimulation (magStim) was analyzed in 5 patients in whom the trigeminal nerve was surgically exposed in the posterior fossa during microvascular decompression of the facial nerve for hemifacial spasm. The trigeminal nerve was stimulated (1) magnetically immediately prior to craniotomy, and (2) electrically near the root exit zone (elREZ) of the nerve from the brainstem. Mean latency differences (delta) of masseter compound muscle action potentials (CMAPs) (delta elREZ minus magStim) were 0.7 (range: +0.3 to +1.3) ms (P less than or equal to 0.05, Wilcoxon-test). From these results, an analysis of anatomical data, and using a trigeminal nerve conduction velocity (NCV) of 50 m/s as reported in the literature, the following conclusions were drawn: the excitation site to magStim (1) is variable among individuals, (2) is located 3.4 (1.6-6.5) cm distal to the trigeminal REZ, and (3) which corresponds to segments of the nerve that are located either within or outside the cerebrospinal fluid (CSF), either proximal or distal to the foramen ovale. These findings are in contrast to those we obtained in a previous study of the facial nerve in which the excitation site was found to be constant among subjects and restricted to the location on the nerve where it exists the high conductivity CSF to enter the high-resistance petrous bone. PMID- 1436648 TI - Extracellular changes of inorganic phosphate are different during spreading depression and global cerebral ischemia of rats. AB - Tissue levels of inorganic phosphate (iP-) and lactate (lac) increase during cerebral ischemia and cortical spreading depression (SD). Since cell membranes become leaky during these insults, iP- and lac were expected to leak into the extracellular space (ECS). In order to find out whether this occurs or does not, a microdialysis (MD) fiber was implanted into the cortex of anesthetized rats and extracellular lactate (lac(e)) and extracellular iP- (iPe-) were determined during various insults. Extracellular lactate increased to about the same extent during ischemia and SD. In contrast, iPe- increased during ischemia but not during SD. Instead, iPe- started to rise after SD and reached its maximum about 45 min later. The distinct pattern of iPe- in comparison to lac(e) during the above mentioned insults points to a qualitative difference of the underlying mechanisms: whereas lac appears within the ECS at any stressful situation, elevation of iP- within the ECS indicates depletion of energy stores in parallel to the lack of control of ion homeostasis. PMID- 1436649 TI - Dimensional analysis of the human EEG and intelligence. AB - The purpose of this study was the determination of the relationship between the dimensional complexity of the electroencephalogam (EEG) and the level of intelligence in humans. In two experiments 34 male subjects were divided into two groups, with high and low levels of intelligence (as measured by the intelligence quotient (IQ)). During a resting phase and various mental imagery conditions the EEG was recorded from several scalp sites. Nonlinear analysis, based on the theory of deterministic chaos, revealed that subjects with high IQs demonstrate higher dimensional complexity of the EEG attractors than subjects with low IQs only during resting conditions. During performance of the imagery tasks the less intelligent subjects increase the complexity of electrical brain dynamics such that IQ-dependency vanishes. The gross (mass) neuronal manifestation of general intelligence seems to depend on task conditions and may be related to the individual brain dynamics only when no specific task is present. PMID- 1436650 TI - Hippocampal nerve growth factor receptor immunoreactivity in patients with Alzheimer's and Parkinson's disease. AB - Using the monoclonal antibody, ME 20.4, against the p75 nerve growth factor (NGF) receptor, NGF receptor-like immunoreactivity has been identified in axonal processes innervating the human hippocampus, where previously a loss of reactivity has been reported in a preliminary study of Alzheimer's disease [10]. In an extended analysis of 15 cases of Alzheimer's disease, the number of NGF receptor positive fibres in the fimbria and alveus was generally decreased compared with age-matched normal groups, in presenile but not senile cases (differentiated by age of onset before or after 65 years). By contrast, in 5 demented Parkinson's disease cases (aged 61-86 years at death) immunohistochemically reactive fibres were consistently minimal or absent. This pattern of NGF receptor loss in the hippocampus most closely reflects the loss of basal forebrain cholinergic neurones, previously reported within the different clinical groups but not by biochemical measures of cholinergic function. It is concluded that even at moderately advanced stages of Alzheimer's disease with onset in the senium, axonal processes and NGF receptor mechanisms may be structurally intact in areas of cholinergic innervation from the basal forebrain, despite evidence of cholinergic dysfunction (decreased choline acetyltransferase (ChAT) and acetylcholinesterase), but that in presenile Alzheimer's and in demented Parkinson's disease cases the receptor declines in conjunction with the loss of subcortical neurones and their processes. The loss of ChAT activity may therefore reflect a dysfunction of the NGF system, in its normal maintenance of the cholinergic phenotype in basal forebrain neurones. PMID- 1436651 TI - N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of memantine in rats. AB - The present study examined in vivo whether memantine exerts muscle relaxant activity via an antagonistic action at N-methyl-D-aspartate (NMDA) receptors. Intraperitoneal (i.p.) administration of memantine, 50-100 mumol/kg, reduced the tonic activity in the electromyogram recorded from the gastrocnemius muscle of spastic mutant rats. This effect was prevented by coadministration of NMDA. Memantine, while not affecting monosynaptic Hoffmann (H)-reflexes, depressed polysynaptic flexor reflexes in anaesthetized rats following i.p. (6.25-100 mumol/kg) or intrathecal (i.t., 10-500 nmol) administration. The latter effect was prevented by i.t. coadministration of NMDA, but not of alpha-amino-3-hydroxy 5-methyl-4-isoxazolepropionic acid (AMPA). These observations suggest that NMDA receptors might be involved in the mediation of the muscle relaxant activity of memantine. PMID- 1436652 TI - Interleukin-6 and leukemia inhibitory factor promote the survival of acetylcholinesterase-positive neurons in culture from embryonic rat spinal cord. AB - Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) promoted the survival of acetylcholinesterase (AChE)-positive neurons in culture from embryonic E15 rat spinal cord. Half of the AChE-positive neurons died during 3-7 days in culture in the absence of IL-6 and LIF. However, IL-6 at a concentration of 5 ng/ml completely prevented the death of AChE-positive neurons. LIF at a concentration of 5 U/ml also stimulated the survival of neurons, although to a lesser extent than IL-6. IL-6 and LIF also increased the numbers of process-bearing neuron-like cells in culture. The dose-dependencies of IL-6 and LIF with regard to the survival of total neuron-like cells were different from those for AChE-positive neurons. PMID- 1436653 TI - Monensin can transport calcium across cell membranes in a sodium independent fashion in the crayfish Procambarus clarkii. AB - Monensin, a Na(+)-selective ionophore, enhances transmitter release when applied to crustacean and frog neuromuscular junctions. Monensin is believed to raise intracellular sodium ([Na+]i) which in turn elevates intracellular calcium ([Ca2+]i). Using the fluorescent indicator fura-2, we measured [Ca2+]i in crayfish Procambarus clarkii presynaptic terminals during monensin application in normal Ringer, zero-calcium Ringer and zero-sodium Ringer to determine if [Ca2+]i increases with monensin application and if so by what mechanism. In normal Ringer, monensin, 10 microM and 100 microM, elevated [Ca2+]i by 440 nM and 7 microM respectively. This rise in [Ca2+]i was dependent on external calcium, as [Ca2+]i did not increase in zero-calcium Ringer. However, in a zero-sodium Ringer, monensin (10 microM) elevated [Ca2+]i by 370 nM. It is important to recognize that monensin, thought to be a sodium-selective ionophore, can transport calcium across the cytoplasmic membrane in a sodium-independent manner. PMID- 1436654 TI - A postsynaptic GABA transporter in rat spinal motor neurones. AB - The plasma membrane uptake system for gamma-amino butyric acid (GABA) is conventionally assumed to be presynaptic, so that after release GABA could be taken up and incorporated into synaptic vesicles for re-use. Using in situ hybridization histochemistry we find that rat spinal motor neurones express GAT 1, a transporter protein for GABA, but that they do not express glutamic acid decarboxylase, the synthetic enzyme for GABA. We conclude that the uptake system is located postsynaptically in these cells. Our observation may explain previous reports where GABA has been detected immunocytochemically in motor neurones. PMID- 1436655 TI - A novel inositol phosphate selectively inhibits vasoconstriction evoked by the sympathetic co-transmitters neuropeptide Y (NPY) and adenosine triphosphate (ATP). AB - Postganglionic sympathetic nerves release norepinephrine (NE) as their primary neurotransmitter at vascular and other targets. However, much evidence supports involvement of additional messengers, co-transmitters, which are co-released with NE upon sympathetic nerve stimulation and thereby contribute to their actions, e.g., vasoconstriction. Two such putative co-transmitters, neuropeptide Y (NPY) and adenosine triphosphate (ATP) have been of particular interest since they fulfill several neurotransmitter criteria. Importantly, hitherto it has been difficult to antagonize vasoconstriction evoked by either NPY or ATP with agents that are devoid of intrinsic activity. The present study describes the ability of a novel inositol phosphate, D-myo-inositol 1,2,6-trisphosphate (Ins[1,2,6]P3; PP 56) to in vitro potently block vasoconstrictor responses elicited by NPY and ATP, but not by NE, as studied in guinea-pig isolated basilar artery. The action of Ins[1,2,6]P3 does not seem to occur through antagonism at NPY- or ATP-receptor recognition sites, labeled by 125I-peptide YY and 35S-gamma-ATP, respectively, in membranes of rat cultured vena cava vascular smooth muscle cells. However, it does involve inhibition of the influx of Ca2+ induced by either co-transmitter in these same vena cava cells. It is proposed that Ins[1,2,6]P3 may be a useful functional antagonist of non-adrenergic component(s) of the vasoconstrictor response to sympathetic nerve stimulation. PMID- 1436656 TI - Oxiracetam prevents the hippocampal cholinergic hypofunction induced by the NMDA receptor blocker AP7. AB - The intracerebroventricular injection of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-7-phosphonoheptanoic acid (AP7) induces an increase of the hippocampal levels of acetylcholine (ACh) which is dose-dependent in the range 1.5-10 micrograms. Similar doses of AP7 failed to affect the ACh content of the striatum. The effect of the i.c.v. administration of 3.5 micrograms AP7 on hippocampal ACh levels was prevented by pretreatment with oxiracetam 100 mg/kg i.p. In the passive avoidance test the i.c.v. administration of 3.5 micrograms of AP7 caused severe amnesia which was antagonized in a dose-dependent manner by the pretreatment with oxiracetam. These results show that oxiracetam prevents the imbalance of cholinergic activity and the amnesia caused by blockade of NMDA receptors. The present study suggests that the hippocampal cholinergic activity is modulated by glutamatergic neuronal pathways and that the functional integrity of both systems is essential for learning and memory processes. PMID- 1436657 TI - Uneven distribution of intracellular Cl- in rat hippocampal neurons. AB - Electrophysiological observations of neurons suggest that perikarya and dendrites differ in local intracellular Cl- concentration ([Cl-]i), that has not been demonstrated yet. Regional [Cl-]i in cultured hippocampal neurons was estimated using a Cl(-)-sensitive fluorescent dye. Calibration showed that perikaryonic [Cl ]i was lower than dendritic [Cl-]i. Ethacrynic acid, an inhibitor of the outwardly directed Cl(-)-pump, increased the perikaryonic but not dendritic [Cl ]i. A decrease in [Cl-]i induced by furosemide or bumetanide, inhibitors of Na+/K+/2Cl- cotransporters, was more prominent in dendrites than in perikarya. These findings suggest that uneven distribution of Cl- is generated by the region specific localization of these transporters. PMID- 1436658 TI - In vitro quantitative autoradiography of [125I]alpha-bungarotoxin binding at the motor end-plates of experimental autoimmune myasthenia gravis. AB - A quantitative evaluation was made of nicotinic acetylcholine receptors (AChR) at the motor end-plates in experimental autoimmune myasthenia gravis (EAMG). Female Lewis rats were immunized with AChR protein purified from electric organs of Narke japonica. The forelimb digit extensor muscle obtained in the chronic stage of the controls and EAMG were studied using [125I]alpha-bungarotoxin, in vitro and autoradiographically. The maximum binding capacity (Bmax) values of the controls and EAMG were calculated to be 237.7 +/- 13.0 fmol/mg (n = 4) and 42.0 +/- 4.1 fmol/mg (n = 4), respectively (P less than 0.001), and the dissociation constant (Kd) values were 11.7 +/- 1.6 nM and 7.6 +/- 0.9 nM, respectively. This in vitro autoradiographic method revealed a quantitative reduction of AChR at the motor end-plates in EAMG. PMID- 1436659 TI - Differential subcellular distribution of PC1, PC2 and furin in bovine adrenal medulla and secretion of PC1 and PC2 from this tissue. AB - The subcellular distribution of PC1, PC2 and furin was determined in bovine adrenal medulla by immunoblotting of fractions obtained by density gradient centrifugation. PC1 and PC2 were found to be confined to chromaffin granules whereas furin (C-terminal-peptide) was absent from these organelles. Stimulation of bovine adrenal medulla by carbamoylcholine chloride induced the secretion of PC1 and PC2. The secreted enzymes had the same molecular size as PC1 and PC2 present in chromaffin granules. PMID- 1436661 TI - Convergence of excitatory inputs from the chorda tympani, glossopharyngeal, and vagus nerves onto inferior salivatory nucleus neurons in the cat. AB - Inferior salivatory nucleus (ISN) neurons were identified by their antidromic spike responses to tympanic nerve stimulation, and their responses to stimulation of the ipsilateral chorda tympani, glossopharyngeal, and vagus nerves were investigated in urethane-chloralose-anesthetized cats. Of the 53 ISN neurons identified, stimulation of at least one of these nerves evoked spike responses in 35 (66%), and 25 (47%) were excited by inputs from more than two stimulated nerves. The mean latencies of the reflex responses evoked by stimulation of the chorda tympani, glossopharyngeal, and vagus nerves were 10.4, 13.7, and 18.9 ms, respectively. PMID- 1436660 TI - Responses of regional cerebral blood flow to intravenous administration of thyrotropin releasing hormone in aged rats. AB - The effects of i.v. administration of thyrotropin releasing hormone (TRH) on regional cerebral blood flow (rCBF) were examined in both healthy adult (3-5 months old) and healthy aged (24-25 months old) male Wistar rats under halothane anesthesia. The rCBFs in 9 different brain regions-cerebral cortex, caudate putamen, hippocampus, thalamus + hypothalamus, superior colliculus, inferior colliculus, cerebellum, pons, and medulla-were measured by [14C]iodoantipyrine method. In the adult rats, i.v. administration of TRH (300 micrograms/kg) produced significant increases in rCBFs in cerebral cortex, caudate putamen, hippocampus, thalamus + hypothalamus and superior colliculus. In the aged rats, the rCBFs in all brain regions measured did not change significantly by TRH administration. From these results, it is suggested that the system involved in TRH-induced vasodilatation of cerebral blood vessels was impaired with aging. PMID- 1436662 TI - Long-term serotonin reinnervation of the suprachiasmatic nucleus after 5,7 dihydroxytryptamine axotomy in the adult rat. AB - We present here immunohistochemical evidence that serotonin (5-HT) reinnervation in the suprachiasmatic nucleus (SCN) of adult rats, after intraventricular administration of 5,7-dihydroxytryptamine, is more extensive than formerly believed. The first fibers appeared at 4 months and developed until more than 7 months. However, comparison with age-matched controls showed that, even 24 months post-lesion, the density of 5-HT innervation remained abnormally low. At the electron microscopic level, many synaptic contacts were found to have been re established. The cellular mechanisms possibly responsible for incomplete 5-HT reinnervation in the SCN are discussed. PMID- 1436663 TI - Modulation of neonatal rat hypoglossal motoneuron excitability by serotonin. AB - The effects of 5-HT on neonatal rat hypoglossal motoneurons (HMs) were studied in two in vitro slice preparations. Serotonin caused either reversible depolarization or the generation of an inward current (I5-HT) in every cell tested. I5-HT persisted after synaptic blockade. In most of the cells tested, the magnitude of I5-HT was independent of membrane potential (-50 to -120 mV), and 5 HT had little effect on input resistance or slope conductance. In addition, 5-HT significantly reduced the amplitude of the post-spike medium-duration afterhyperpolarization. This reduction probably contributed to the resulting increase in the slope of the relationship describing the steady-state firing frequency response to injected current (f-I) observed in the presence of 5-HT. Thus, 5-HT increases the excitability of neonatal HMs via at least two different postsynaptic mechanisms. PMID- 1436664 TI - Stimulation of the nucleus basalis of Meynert increases cortical cerebral blood flow without influencing diameter of the pial artery in rats. AB - The effects of focal electrical stimulation of the nucleus basalis of Meynert (NBM) and hypercapnia on diameter of the pial artery and regional cerebral blood flow (CBF) in the parietal cortex were examined in urethane-anesthetized rats. The diameter of pial artery was measured using the video microscope and cortical CBF was measured using the laser Doppler flowmetry. Hypercapnia at 10% of end tidal CO2 concentration caused significant increases in diameter of the pial artery and cortical CBF. Electrical stimulation of the NBM (with parameters of 200 microA, 50 Hz, 0.5 ms, for 1 min) produced a significant increase in cortical CBF, but did not influence the diameter of pial artery. The results suggest that cholinergic fibers originating in the NBM do not contribute to neural vasodilatation of the pial artery, although they induce neural vasodilation of parenchymal blood vessels which results in an increase in CBF in the parietal cortex. PMID- 1436665 TI - Hypoglycemia-activated K+ channels in hippocampal neurons. AB - Channels linking the electrical and metabolic activities of cells (KATP channels) have been described in various tissues, including some brain areas (hypothalamus, cerebral cortex and substantia nigra). Here we report the existence in hippocampal neurons of K+ permeant channels whose activity is regulated by extracellular glucose. They are open at the cell resting potential and respond to transient hypoglycemia with a reversible increase in activity. The one type so far characterized has a conductance of approximately 100 pS in isotonic K+, is inhibited by the sulphonylurea glibenclamide (1 microM), and is activated by the potassium channel opener lemakalim (0.1-1 microM). These data provide a direct demonstration of the presence, in hippocampal neurons, of glucose-sensitive channels that could belong to the KATP family. PMID- 1436666 TI - Volume regulation of single astroglial cells in primary culture. AB - Relative volume variations in cultured astrocytes were examined by microspectrofluorimetry after loading the cells with the highly fluorescent intracellular probes 2,7-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF/AM) or fura-2/AM. At their isosbestic points, 450 nm and 358 nm, respectively, the probes were ion-insensitive and the fluorescent signals emitted related only to the intracellular dye concentration. By varying the excitation wavelengths, changes in intracellular pH or Ca2+ transients could be recorded simultaneously with the relative volume variations of the individual cells. After exposure to a hypotonic buffer, type 1 astrocytes swelled within 30 s and subsequently underwent regulatory volume decrease (RVD). When exposed to a hypertonic buffer, the astrocytes shrunk and exhibited regulatory volume increase (RVI). One mM glutamate induced an increase in astrocyte volume in 60 sec and evoked cytosolic Ca2+ transients but did not change intracellular pH. PMID- 1436667 TI - Distribution of cannabinoid receptor messenger RNA in the human brain: an in situ hybridization histochemistry with oligonucleotides. AB - The distribution of the messenger RNA coding for the recently cloned cannabinoid receptor was studied for the first time in the human brain using in situ hybridization histochemistry and oligonucleotides probes. Microscopically, positive neurons were observed in the layers II-III and V-VI of the cerebral cortex, and in the hilus and the different dendritic layers of the dentate gyrus and Ammon's horn of the hippocampus. No additional microscopic signal could be detected. Macroscopically, a slight hybridization signal, visible on the films after 2 months exposure and which disappears after RNAse treatment, was also found throughout all layers of the cortex, in the pyramidal cell layer of the hippocampus, in the caudate and putamen, and in the granular and molecular layers of the cerebellum. No signal was detected in the brainstem, spinal cord and white matter. In conclusion, the cannabinoid receptor mRNA neuronal localizations here demonstrated in the human brain confirm our previous report in the rat, taking into account that the levels of the transcripts found in the human were lower than in the rat brain. PMID- 1436668 TI - Interconnections between the pretectum and visual thalamus in reptiles, Caiman crocodilus. AB - Interconnections between the visual thalamus and the pretectum were investigated in one species of reptiles, Caiman crocodilus, by injections of horseradish peroxidase into nucleus rotundus. Nucleus pretectalis was identified as a major target of rotundal efferents as well as a significant input to nucleus rotundus. The presence of a pretectal nucleus with neural connections and topographic location similar to nucleus pretectalis of Caiman has been described in lizards and pigeons. Taken together, these observations suggest that this pretectal nuclear group and its associated fiber path may be a feature common to all non mammalian amniotes. PMID- 1436669 TI - Quantification of D-aspartate in normal and Alzheimer brains. AB - Using a new procedure to hydrolyze proteins without provoking racemization of the amino acids and using enzymatic methods to determine D- and L-aspartate (Asp), we have quantified the content of protein-bound D-aspartate (both D-aspartic acid and D-asparagine) of human brain white and gray matter proteins from normal and Alzheimer subjects. The D-enantiomer is present in brain proteins at mean concentrations between 0.48 and 0.90 mumol/g of wet tissue, corresponding to concentrations 34-82 times lower than that of L-aspartate. The highest levels of D-aspartate were found in Alzheimer gray matter (0.60-0.90, mean 0.69 mumol/g of wet tissue). When expressed as the percentage of total (i.e. D- plus L-) aspartate, %D = [D/(D + L)] x 100, the Alzheimer brains show a significantly higher content of D-aspartate in both gray matter (2.08%) and white matter (1.80%) than in the corresponding tissues of normal brains (1.65% in gray, 1.58% in white). PMID- 1436670 TI - Mating behavior induces selective expression of Fos protein within the chemosensory pathways of the male Syrian hamster brain. AB - The effect of mating behavior on the expression of Fos protein was analyzed within the chemosensory pathways of the male Syrian hamster brain. Following a single mating test, the number of Fos-immunoreactive (Fos-ir) neurons increased within the amygdala, bed nucleus of the stria terminalis and medial preoptic area. The mating-induced pattern of Fos expression within these brain regions shows a strong correlation with the sites of lesions that eliminate or alter mating behavior. In addition, Fos expression was increased within the paraventricular nucleus of the hypothalamus. These results provide the first demonstration of a dynamic and selective pattern of neuronal activity within specific nuclei known to be essential for mating behavior in the male Syrian hamster. PMID- 1436671 TI - Quantification of plaque types in sulci and gyri of the medial frontal lobe in patients with Alzheimer's disease. AB - beta-Amyloid protein (beta A4) deposition was characterised in the sulci and gyri of frontal cortex in 14 cases of Alzheimer's disease. A quantitative study was made of two distinct plaque sub-types (diffuse and classic) using immunocytochemistry and image analysis using a discriminant function design. As reported previously more beta A4 was observed in sulci than gyri. Diffuse plaques were more numerous than classic plaques in sulci and gyri (P less than 0.01). Classic plaques were more abundant in the sulci (P less than 0.01). Increased beta A4 deposition in the sulci is accounted for by increased numbers of classic plaques. No correlation was observed between the numbers of diffuse and classic plaques in either region. Our data suggest that the two plaque types form discrete populations and that their evolution is governed by distinct pathophysiological parameters. PMID- 1436672 TI - Expression of neurofibromin, the neurofibromatosis 1 gene product: studies in human neuroblastoma cells and rat brain. AB - Neurofibromatosis type 1 (NF1) is one of the most frequent Mendelian disorders in man and one of the most common autosomal dominant disorders affecting the nervous system. The NF1 gene has recently been cloned, and shows homology to the GTPase activating protein. In order to characterize the NF1 gene product, now called neurofibromin, we raised polyclonal antibodies against C- and N-terminal regions of neurofibromin and analyzed the protein by Western blot analysis and immunohistochemical studies of rat brain. PMID- 1436673 TI - Thalamocortical connections of rat posterior parietal cortex. AB - The neuronal connections of rat posterior parietal cortex (PPC) have been examined using retrograde fluorescent axonal tracers. We have found that PPC receives thalamic input predominantly from the lateral posterior and lateral dorsal nuclei, and not from the ventrobasal nucleus, which projects to the rostrally adjacent hindlimb cortex, or from the dorsal lateral geniculate nucleus, which projects to the caudally adjacent visual association area. PPC has reciprocal corticocortical connections with medial agranular cortex and orbital cortex; together, these three cortical areas may function as a network for directed attention in rats. PMID- 1436674 TI - Spinal locomotor activity in acutely spinalized cats induced by intrathecal application of noradrenaline. AB - In this study we present a method of intrathecal drug administration in the acute spinal cat. A thin tube introduced into the subarachnoid space below the spinal cord was used for local drug administration. Noradrenaline reduced short-latency and provoked long-latency reflexes following high threshold afferent stimulation. Topical application of noradrenaline to the spinal cord was also able to induce and maintain locomotion. Our results strengthen the notion that noradrenergic systems play an important role in motor control. In addition, the present report introduces a protocol in the acute spinal cat, which combine the benefits associated with direct application of drugs as used in vitro experiments with the advantages of using the well investigated in vivo cat spinal cord preparation. PMID- 1436676 TI - Enriched environment primes forebrain choline acetyltransferase activity to respond to learning experience. AB - Weanling rats were raised in an enriched or an impoverished environment. The enriched rats subsequently learned the Morris water maze faster than their impoverished counterparts. The enriched rats, both maze-trained and untrained, showed higher choline acetyltransferase (ChAT) activity in the caudate than did the impoverished, untrained rats. Maze training increased caudate ChAT in impoverished rats. Enriched but not impoverished rats showed increased hippocampal and anterior cortical ChAT activity after maze training. Thus, enrichment causes a long-lasting increase in caudate acetylcholine (Ach) synthesis and it also primes cortex and hippocampus to respond to a training experience with increased Ach synthesis. PMID- 1436675 TI - Effect of furosemide treatment on the central and peripheral pressor responses to cholinergic and adrenergic agonists, angiotensin II, hypertonic solution and vasopressin. AB - The present study was performed to investigate the effect of treatment with furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injections of cholinergic (carbachol) and adrenergic (norepinephrine) agonists, angiotensin II (ANGII) and hypertonic saline (HS, 2 M NaCl). The changes induced by furosemide treatment on the pressor response to intravenous (i.v.) norepinephrine, ANGII and arginine vasopressin (AVP) were also studied. Rats with a stainless-steel cannula implanted into the lateral ventricle (LV) were used. Two injections of furosemide (30 mg/kg b.wt. each) were performed 12 and 1 h before the experiments. Treatment with furosemide reduced the pressor response induced by carbachol, norepinephrine and ANGII i.c.v., but no change was observed in the pressor response to i.c.v. 2 M NaCl. The pressor response to i.v. ANGII and norepinephrine, but not AVP, was also reduced after treatment with furosemide. These results show that the treatment with furosemide impairs the pressor responses induced by central or peripheral administration of adrenergic agonist or ANGII, as well as those induced by central cholinergic activation. The results suggest that the treatment with furosemide impairs central and peripheral pressor responses mediated by sympathetic activation and ANGII, but not those produced by AVP. PMID- 1436677 TI - Unilateral EEG activation during sleep in the Cape fur seal, Arctocephalus pusillus. AB - Sleep and wakefulness on the land were studied electrophysiologically in one adult female Cape fur seal (Arctocephalus pusillus). In two 24-h sessions, slow wave sleep and paradoxical sleep averaged 27.4% and 4.6% of the total recording time. Almost 40% of the total slow-wave sleep time was accounted for episodes with well-defined interhemispheric ECoG asymmetry. PMID- 1436678 TI - Eyeblinks evoke potentials in the occipital brain region. AB - The subjects performed voluntary eyeblinks under illuminated and dark laboratory conditions. 32-channel EEG recordings were averaged in relation to the eyeblinks and a brain electric source analysis (BESA) was performed. Two dipoles located near the eyeballs and a third dipole in the occipital region of the brain were found to explain the scalp potentials. The frontally located potentials described electromechanical potentials associated with lid movements and simultaneous eye movements. The occipitally located dipole explained a visually evoked potential with a first peak at about 180 ms after the maximum of the frontal blink potential. The visually evoked potential was observed only under illumination and was probably caused by changes in luminance during the eyeblinks. PMID- 1436679 TI - Glial fibrillary tangles with straight tubules in the brains of patients with progressive supranuclear palsy. AB - A recent report has described the appearance of silver positive, tau immunoreactive astrocytes in the brains of patients with progressive supranuclear palsy (PSP) (Neurosci. Lett., 135 (1992) 99-102). In this study we confirmed this finding in two cases of PSP by using Bodian silver staining and immunohistochemistry with antibody to human tau protein. By electron microscopy we demonstrated that fibrillary masses present in these unique astrocytes were made up of straight tubules that were indistinguishable from those of neurofibrillary tangles of PSP. The term 'glial fibrillary tangle' was proposed for these structures. PMID- 1436680 TI - Protease 'Clipsin' extract activity reflects demographic characteristics of human brain. AB - 'Clipsin' and other peptide bond hydrolase activities that appear to be integral membrane proteins, including two implicated in the formation of the histological hallmarks of Alzheimer's disease, were assayed in the frontal and parietal cortex from a large (n = 45) series of postmortem human brains. Tissues were extracted sequentially with detergent-containing and low ionic strength buffers. The final extracts obtained with detergent-high ionic strength buffer were assayed for peptide-bond hydrolase activity using radiolabelled casein and four chromophore linked peptide substrates. Hydrolysis of N-succinyl-Ala-Ala-Pro-Phe-p nitroanilide and alpha-casein showed evidence of sensitivity to the presence of Alzheimer's disease (n = 22) and some of the seven other demographic features (postmortem delay; mode of death in the case of one substrate) of the brain samples considered. By contrast, activity towards carbobenzoxy(Z)-Leu-Leu-Glu-2 naphthylamide, Z-Val-Lys-Met-4-methyl-coumaryl-7-amide and Z-Val-Lys-Lys-Arg-4 methoxy-2-naphthylamide were independent of all factors. The results are discussed in terms of damage to a sub-population of protease-containing membranes. PMID- 1436681 TI - Oestrogen infusions into the amygdala potentiate excitatory transmission from the accessory olfactory bulb to tuberoinfundibular arcuate neurones in the mouse. AB - We have previously shown that oestrogen increases the percentage of tuberoinfundibular (TI) arcuate neurones that respond to electrical stimulation of the accessory olfactory bulb (AOB). This study focuses on the amygdala as a possible site for the hormonal modulation of AOB input to TI arcuate neurones. Local infusions of 17 beta-oestradiol (30 pmol) into the amygdala of ovariectomized female mice significantly potentiated excitatory responses of TI arcuate neurones to AOB stimulation. This effect appeared rapidly (less than 10 min) after infusion. The inactive oestrogen isomer, 17 alpha-oestradiol, infused in the same manner, was without effect. These results suggest that oestrogen acts directly on amygdala neurones, thereby modulating olfactory information relayed along the vomeronasal pathway to TI arcuate neurones. PMID- 1436682 TI - Two populations of cells that express preprocholecystokinin mRNA in ventral periaqueductal grey. AB - Cells expressing preprocholecystokinin (CCK) mRNA in the rat midbrain periaqueductal grey area and Edinger-Westphal nucleus were analysed using in situ hybridization combined with liquid emulsion techniques. Semi-quantitative image analysis revealed that there were two populations of cells which expressed CCK mRNA. The first group of cells were large and heavily labelled and were confined to the Edinger-Westphal nucleus. The second group of cells were small and lightly labelled and were found scattered throughout ventral parts of the anterior periaqueductal grey. PMID- 1436683 TI - A possible neural source of nitric oxide in the rat penis. AB - NADPH diaphorase staining was used to indicate the presence of nitric oxide synthase (NOS) in whole mounts of rat major pelvic ganglion (MPG) and sections of rat penis. Many stained neurons were observed in the MPG and were distributed in a manner identical to that of retrogradely labelled penile neurons described previously. Staining was also observed within many axons of the penile (cavernous) nerve and in varicose terminals associated with various tissues of the penis. The results suggest that many, if not all, penile neurons of the MPG contain NOS and that a neural source of NO within the penis is likely. PMID- 1436684 TI - Post-training medial septal stimulation improves spatial information processing in BALB/c mice. AB - The experiment reported here was designed to highlight the effects of medial septal nucleus electrical stimulation on memory processes. To that end, we have used a learning task carried out in a 4-hole board in which animals were successively presented with the location of 2 baited holes. Under these conditions, the consequence of a weak stimulation (30 microA peak to peak, 80 s in duration) applied 30 s after acquisition of these 2 separate spatial informations was assessed on a retention test 24 h later. The results indicated that performance of stimulated animals was improved by medial septal stimulation as shown by an increase in the time duration of exploration of the second previously baited hole. However, post-training stimulation also produced a significant avoidance of the first previously baited hole not observed in the control groups. These results suggest that medial septal stimulation improves retroactive inhibition involved in working memory processes, thus leading to better retention of this kind of learning situation. PMID- 1436686 TI - Strong immunoreactivity of beta-amyloid precursor protein, including the beta amyloid protein sequence, at human neuromuscular junctions. AB - At the postsynaptic domain of the human neuromuscular junction (NMJ), we have demonstrated strong concentrations of the N-terminus 45-62, C-terminus 676-695 and beta-amyloid protein sequences of beta-amyloid precursor protein (beta APP). We used well-characterized monoclonal and polyclonal antibodies for co localization with three other postsynaptic proteins, applying double and triple fluorescence labeling. Strong immunoreactivity of all three beta APP sequences was found at all NMJs identified by bound alpha-bungarotoxin (alpha BT), where they co-localized with alpha BT and with immunoreactive desmin and dystrophin, which are postsynaptic proteins of human NMJs. This appears to be the first demonstration of beta APP sequences concentrated postsynaptically at human NMJs. beta APP may have a role in normal junction biology and possibly in some diseases affecting NMJs. PMID- 1436685 TI - Serotonergic modulation of the respiratory rhythm generator at birth: an in vitro study in the rat. AB - In order to investigate the mechanisms through which serotonin (5-HT) modulates the activity of the respiratory rhythm generator, respiratory activity was recorded from cervical ventral roots of the superfused isolated brainstem-spinal cord preparation of the newborn rat. Replacing the normal bathing medium by a medium containing 5-HT (30 microM) increased the respiratory frequency by 70% of the control value. Intact pontomedullary structures are necessary for this effect to take place, however, since the 5-HT-induced increases in respiratory frequency were no longer observed after elimination (section and electrolytic lesion) of the caudal ventro-lateral pons containing the A5 areas. Local applications of 5 HT (dual bath, microdialysis and microinjection experiments) revealed, however, that 5-HT acts at the medullary level and that its effects are not due to a diffuse action on all the neurons of the medullary respiratory centers but to a specific action focusing on structures located in the rostral ventro-lateral medulla. PMID- 1436687 TI - Allopurinol preserves cerebral energy metabolism during perinatal hypoxia ischemia: a 31P NMR study in unanesthetized immature rats. AB - The effects of high dose allopurinol (ALLOP) pretreatment on the cerebral energy metabolism of unanesthetized 7-day-postnatal rats during exposure to 3 h of cerebral hypoxia-ischemia were serially quantitated using non-invasive 31P NMR spectroscopy. Adenosine triphosphate, integrated over the last 2 h of hypoxia and expressed as a fraction of baseline, was 0.73 +/- 0.16 with ALLOP pretreatment (200 mg/kg s.c.) compared to 0.52 +/- 0.05 for saline pretreatment (P = 0.001). Inorganic phosphate/phosphocreatine (Pi/PCr), integrated over the same time interval, was 2.63 +/- 1.23 relative to baseline with ALLOP versus 5.13 +/- 1.45 for saline-treated pups (P less than 0.0005). We suggest that the neuroprotection achieved with high dose ALLOP pretreatment may be attributed in part to preservation of energy metabolites. PMID- 1436688 TI - Metallothionein immunoreactivity is increased in the spinal cord of patients with amyotrophic lateral sclerosis. AB - Sections of the spinal cord from 10 patients with classic amyotrophic lateral sclerosis and from 10 control cases were examined by immunocytochemical methods to localize metallothionein. Metallothionein immunoreactivity was seen in the nucleus and cytoplasm of a subset of astrocytes, largely confined to the gray matter. Also, diffuse gray matter staining was observed, probably representing small glial fibers. Astrocytic metallothionein immunoreactivity (P less than 0.01) and strong gray matter matrix staining (P less than 0.03) was increased in the spinal cords from patients with amyotrophic lateral sclerosis. Although compatible with induction by metals, increased metallothionein expression in the spinal cords from patients with amyotrophic lateral sclerosis may also have resulted from inflammation or gliosis. PMID- 1436689 TI - Comparison of spontaneous motor pattern generation in non-hemisected and hemisected mouse spinal cord. AB - Spontaneous electromyogram (EMG) patterns in the gastrocnemius (G) and tibialis anterior (TA) muscles of spinal cord-hindlimb explants from neonatal mice were investigated. Compared to non-hemisected explants, neither longitudinal hemisection of the spinal cord nor hemisection plus transection at L1 significantly altered the incidence of spontaneous motor rhythm. Therefore, not only does each half of the neonatal spinal cord contain sufficient circuitry to generate motor rhythm, but the more reduced preparations were just as likely to produce such activity. Hemisected preparations, however, exhibited slower rhythm, perhaps due to the loss of excitatory commissural connections. No correlation was found between the number of cycles in a rhythmic sequence and cycle period. In hemisected as well as non-hemisected explants, sequences of spontaneous EMG rhythm occurred in either the G or TA muscle, but not in both muscles simultaneously. Consequently, cycle-to-cycle alternation between rhythmic bursting in the G and TA muscles was not observed. The excitability in such preparations was apparently insufficient for maintained activations of both muscles (either for cycle-to-cycle alternation or for co-contraction). PMID- 1436690 TI - Insulin protects brain tissue against focal ischemia in rats. AB - The influence of insulin on the infarct volume due to middle cerebral artery (MCA) occlusion was investigated in rats. A small dose of insulin (1 unit/kg) was injected i.p. just after MCA occlusion. The infarct areas were measured by planimetry from brains perfused with 2,3,5-triphenyltetrazolium-chloride (TTC) 48 h after the occlusion. Systemic variables were measured before and at various times after ischemia. The comparison between insulin-treated (n = 14) and control (n = 13) rats provided evidence that insulin significantly reduced the infarct volume due to MCA occlusion. As insulin minimally and transiently decreased blood glucose, the present results suggest that insulin exerts a beneficial effect directly on the central nervous system. PMID- 1436691 TI - Retinal ischemia induced by occlusion of both common carotid arteries in rats as demonstrated by electroretinography. AB - In 2 models of reduced cerebral blood flow-permanent occlusion of the vertebral arteries plus transient occlusion of the common carotid arteries (4VO) and transient clamping of the common carotid arteries (BCCA)-the acute effects on the electrical function of the retina were monitored by recording the photopic electroretinogram. During both 4VO and BCCA the amplitude of the b-wave was reduced. Within 30 min of reperfusion after 4VO and after BCCA the b-wave had fully recovered. In contrast, the a-wave was not affected by either treatment. The data suggest that occlusion of common carotid arteries leads to retinal ischemia and might represent a useful model of amaurosis fugax. PMID- 1436692 TI - Acetylcholine synthesis is modulated by acetylcholine content of cytosolic fraction but not by that of releasable fraction. AB - Synthesis and release of acetylcholine (ACh) in the rat hippocampal slices were examined to clarify the mechanism of modulation of ACh synthesis. Treatment with 2-(4-phenylpiperidino)cyclohexanol (AH5183, 50 microM), an inhibitor of ACh transport from cytosol to synaptic vesicles, inhibited the increase in ACh content of the membrane-bound fraction which is readily releasable, but did not affect the cytosolic ACh content. Under these conditions, the total ACh content reached a plateau value. These results indicate that ACh synthesis is modulated by cytosolic ACh content but not by the vesicular fraction. PMID- 1436693 TI - Axonal sprouting induced in the sciatic nerve by the amyloid precursor protein (APP) and other antiproteases. AB - Protease inhibition is the mechanism by which some trophic factors promote the extension of neurites. In the rat sciatic nerve, we assessed the ability to induce sprouts of the APP isoform that embodies the Kunitz antiprotease domain and other antiproteases. With the electron microscope, axonal sprouts were found when antiproteases were supplied but not after administration of inactive substances. We conclude that axons have a drive to sprout which can be released by the unbalance of an extracellular protease-antiprotease system. We propose that this system is involved in the pathogenesis of Alzheimer's disease. PMID- 1436694 TI - Presence of abnormally phosphorylated Tau proteins in the entorhinal cortex of aged non-demented subjects. AB - An immunoblot study was performed in several cortical samples from non-demented aged controls and compared with those from Alzheimer patients, using antibodies against Tau 55, 64 and 69, which are specific and reliable markers of the neurofibrillary degeneration of the Alzheimer type. The immunodetection of Tau 55, 64 and 69 was positive in all cortical areas from Alzheimer patients, in the entorhinal cortex from each control aged more than 65 but not in cortical samples from younger controls. We demonstrate that the entorhinal cortex is the most vulnerable neuronal population in aging and that the biochemical dysfunctions observed in this area are typically of the 'Alzheimer-type'. PMID- 1436695 TI - Denervation of dopaminergic neurons with 6-hydroxydopamine increases nerve growth factor content in rat brain. AB - Denervation of dopaminergic neurons by intra nigral injection of 6 hydroxydopamine (6-OHDA) increased nerve growth factor (NGF) content in the cortex and hippocampus, both of which are innervated by cholinergic neurons. The increase continued during an observation period of 0.5-28 days after the lesion. The time course of changes in NGF content was quite different from that of cholinergic neuron denervation. The decreased dopamine content produced in the striatum by 6-OHDA injection was not recovered during the observation period. These results suggest that dopaminergic neuron damage may affect NGF synthesis. PMID- 1436696 TI - Low calcium/high magnesium medium increases activities of hypothalamic arcuate and suprachiasmatic neurons in brain tissue slices. AB - Extracellular single-unit recording was conducted in hypothalamic arcuate (ARC) and suprachiasmatic nucleus (SCN) in rat brain slices. The perifusion medium was switched from normal artificial cerebrospinal fluid (ACSF) to ACSF containing low Ca2+ and high Mg2+ to test the effect of extracellular calcium on the spontaneous activities of these neurons and their responses to some test agents. It was found that almost all of the ARC and SCN units tested increased their firing rates in low Ca2+, high Mg2+ ACSF, and exhibited more significant responses to excitatory test agents. The effects of low Ca2+, high Mg2+ ACSF were repeatable and reversible. The results suggest that extracellular Ca2+ is essential in maintaining the membrane stability of most hypothalamic neurons and most agents tested are acting postsynaptically on the unit recorded. PMID- 1436697 TI - The type III calcium/calmodulin-sensitive adenylyl cyclase is not specific to olfactory sensory neurons. AB - A cDNA clone for type III adenylyl cyclase was originally isolated from a rat olfactory cDNA library and Northern analysis using total RNA suggested that the expression of the type III mRNA may be limited to the olfactory epithelium (Bakalyar and Reed, Science, 250 (1990) 1403-1406). In this study, the distribution of type III adenylyl cyclase mRNA in a number of bovine tissues and cultured cells was examined by Northern analysis using poly(A)+ RNA. Type III adenylyl cyclase mRNA was expressed in brain, spinal cord, adrenal medulla, adrenal cortex, heart atrium, aorta, lung, retina, 293 cells and PC-12 cells. Furthermore, the Ca2+ sensitivity of adenylyl cyclase activity in 293 cells indicated the presence of type III adenylyl cyclase. These data indicate that expression of the type III adenylyl cyclase is not limited to olfactory tissues, and that this enzyme probably has a number of physiological functions in addition to olfactory signal transduction. PMID- 1436698 TI - Local radiolabeling of the 68 kDa neurofilament protein in rat sciatic nerves. AB - Rat sciatic nerve segments, 4.5 cm distal to the dorsal root ganglion (DRG), were incubated in vivo with [35S]methionine. Fluorography of 2-D polyacrylamide gels of the nerve proteins demonstrated the labeling of the 68-kDa neurofilament protein, which was identified by immunoblotting. This experimental design excludes the dorsal root ganglion as the source of the radiolabeled neurofilament protein and suggests that this neuron-specific protein may be synthesized in axons. PMID- 1436699 TI - Delayed degeneration of the optic tract and neurons in the superior colliculus after forebrain ischemia. AB - Neuronal damage induced by 15-min forebrain ischemia was investigated in adult rats 1-5 days (short-term group) and 1-5 months (long-term group) after the initial ischemic attack. In addition to the vulnerable areas reported previously, we observed that the optic tract was also very susceptible. Degeneration of the optic tract and subsequent transsynaptic cell death in the superior colliculus developed slowly and was observed only in the long-term group. The delayed, progressive neuronal damage in this sensory system may serve as a suitable model to investigate the mechanisms of long-term changes in the injured brain. PMID- 1436700 TI - Tedisamil blocks a calcium-dependent potassium channel in cultured motoneurons. AB - A calcium-dependent potassium channel K(Ca) has been isolated in mouse motoneurons. With physiological concentrations of potassium across inside-out patches, a 100 pS K(Ca) channel was activated when the bath solution of Ca2+ was in excess of 1 microM. Introduction of the drug tedisamil, a blocker of repolarizing potassium channels in cardiac cells, at concentrations in the range 0.2-10 microM, caused a dose-dependent decrease in the mean open times for K(Ca). The drug action was consistent with open channel block of K(Ca) with an onward (blocking) rate constant of 6 x 10(7) M-1 s-1. Tedisamil, at concentrations of 1 microM and 5 microM, also blocked the K(Ca) channel when applied to outside-out patches with a similar potency as found with internal application. A large conductance K(Ca) channel in hippocampal neurons is also blocked by a number of putative Class III antiarrhythmic drugs, including tedisamil; thus, these agents may have utility in the characterization of the properties of K(Ca) channels in various cells. PMID- 1436701 TI - GABAergic afferents modulate proenkephalin mRNA expression in the guinea pig hypothalamic magnocellular dorsal nucleus. AB - The proenkephalin (PE) gene expression within Met-enkephalin (ME) neurons of the guinea pig magnocellular dorsal nucleus (MDN) was measured following activation of GABAergic transmission by aminooxyacetic acid treatment (AOAA). A combination of preembedding ME immunocytochemistry and PE in situ hybridization was used to investigate PE mRNA and enkephalin immunoreactivity levels. In perikarya of the MDN, chronic AOAA-treatment resulted in an important decline in PE mRNA signal ( 128%). In double-labeled neurons, the PE mRNA decrease was associated to an increase in ME immunoreactivity. These results indicate that the increase in ME immunoreactivity in the MDN following AOAA-treatment is not due to a rise in PE gene transcription. This study provides additional morphological evidence supporting a role for GABA in modulating the enkephalinergic hypothalamoseptal tract of the guinea pig. PMID- 1436702 TI - Mapping of c-fos expression elicited by pure tones stimulation in the auditory pathways of the rat, with emphasis on the cochlear nucleus. AB - C-fos expression was mapped in the auditory pathways of rats, stimulated acoustically with pure tones. In the cochlear nucleus, two clusters of c-fos-like immunoreactive neurons, located respectively in the caudal part of the dorsal cochlear nucleus and in the granular cell region, did not show clear systematic shift in their position as a function of the tones frequency. On the other hand, more rostrally in the dorsal cochlear nucleus, a cluster of c-fos-like positive neurons moved progressively from dorsal to ventral for decreasing tones frequency. In the posteroventral cochlear nucleus, another cluster of c-fos-like positive neurons was observed, whose position also varied with tones frequency. Surprisingly, no or very rare c-fos-like immunoreactive neurons were present in the anteroventral cochlear nucleus and in the superior olivary complex. In the inferior colliculus, however, c-fos-like immunoreactive neurons formed clear isofrequency contours, shifting from dorsolateral to ventromedial for increasing tones frequency. In the medial geniculate body c-fos-like immunostaining was restricted to the medial and dorsal divisions while the ventral division was free of labeling. The cause of this differential labeling along the auditory pathways is at present unknown but may eventually provide clues as to physiological differences in parallel auditory pathways. PMID- 1436703 TI - Increased brain concentrations of a neurotoxin, 3-hydroxykynurenine, in Huntington's disease. AB - Concentrations of the neurotoxic tryptophan metabolite, 3-hydroxykynurenine, were determined in brain tissue taken post-mortem from patients with Huntington's disease and Alzheimer's disease. 3-Hydroxykynurenine was substantially and significantly increased in all three brain areas studied in Huntington's disease, but not significantly increased in the cortex in Alzheimer's disease, when compared to matched controls. These results demonstrate a possible dysfunction of tryptophan metabolism, via the kynurenine pathway, in Huntington's disease. PMID- 1436704 TI - Histamine stimulates exocytosis in a sub-population of bovine adrenal chromaffin cells. AB - Both nicotinic stimulation and histamine are able to raise cytosolic free calcium concentration in the majority of cells in a population of bovine adrenal medullary chromaffin cells to comparable levels. Nevertheless, histamine induces much less catecholamine secretion than does nicotine. In order to test whether this is due to heterogeneity in the responses of chromaffin cells to histamine we examined exocytosis in response to nicotine and histamine using an immunofluorescence method based on staining with anti-DBH to detect inserted secretory vesicle membrane. The results show that while up to 98% of the chromaffin cells in culture undergo exocytosis in response to nicotine, histamine stimulates exocytosis in only a sub-population of cells. PMID- 1436705 TI - D2 dopamine receptor localization on striatonigral neurons. AB - Two major pharmacological classes of dopamine receptors exist in the central nervous system. These receptors have been designated as D1 or D2 based upon their differing pharmacology and influence on the cyclic AMP second messenger system. Different genes for the D1 and D2 dopamine receptors have been isolated and are found to be expressed in high abundance. Within the neostriatum, however the cellular distribution of the dopamine receptors is equivocal. Dopamine receptors are the targets for drugs used to treat neurological dysfunctions such as Parkinson's disease and schizophrenia, and thus knowledge of their specific cellular location is important for devising future therapeutic manipulations. Using retrograde labeling methods combined with immunofluorescence of various receptor amino acid sequences, this study has examined the postsynaptic distribution of striatal D2 dopamine receptors. We have found that the D2 dopamine receptor can be visualized on a minimum of 60% of the neurons projecting from the neostriatum to the substantia nigra. However, some 65% of all D2 receptor positive cells are represented by other intrinsic neurons of this basal ganglia nucleus. PMID- 1436706 TI - Cell adhesion molecule L1 guides cell migration in primary reaggregation cultures of mouse cerebellar cells. AB - We demonstrate a new assay in vitro using reaggregated cerebellar neurons in order to test the role of the L1 molecule in migration events. Cells other than neurons were eliminated in these cultures. Cerebellar neuron reaggregates plated on L1 molecule substrates migrated at rates similar to those observed in vivo. This migration was blocked by anti-L1 antibody. These findings suggest that this culture could provide a useful system with which to directly study relationships between neuron migration and adhesion molecules. PMID- 1436707 TI - Expression of the mRNA for the rat NMDA receptor (NMDAR1) in the sensory and autonomic ganglion neurons. AB - The distribution of NMDA receptor (NMDAR1) on neurons in the peripheral ganglia was examined in the adult rat by in situ hybridization. NMDAR1 mRNA was expressed in all neurons in the sensory and autonomic ganglia examined; in the dorsal root, trigeminal, nodose, superior cervical, and sphenopalatine ganglia. Possible roles of the NMDA receptor on the sensory and autonomic ganglion neurons are discussed. PMID- 1436708 TI - Glutathione prevents 2,4,5-trihydroxyphenylalanine excitotoxicity by maintaining it in a reduced, non-active form. AB - 2,4,5-Trihydroxyphenylalanine (TOPA) in aqueous solution has been shown to form an non-N-methyl-D-aspartate (non-NMDA) agonist and neurotoxin, TOPA quinone. We examined whether the endogenous chemical reductant glutathione (GSH) could abolish the agonist properties of TOPA and block its excitotoxicity in rat cortical neurons in culture by preventing the formation of TOPA quinone. The oxidative formation of TOPA quinone from TOPA (30-500 microM) at pH 7.2 was measured spectrophotometrically. Using glutathione (0.05-3 mM) as the reducing agent, we found that the optimal [GSH]:[TOPA] ratio which significantly retarded TOPA quinone formation was 10:1. Thus, 3 mM GSH prevented whole-cell currents induced by a solution of 300 microM TOPA but did not affect currents elicited by 300 microM kainate. In addition, 2 mM GSH protected neurons from the toxic effects of 200 microM TOPA, but was not effective against 200 microM NMDA. These results suggest that the presence of endogenous reductants may limit the toxicity of TOPA. PMID- 1436709 TI - IGF-II mRNA expression in LI human glioblastoma cell line parallels cell growth. AB - A human glioblastoma cell line was found to express in vitro mRNA transcripts specific for insulin-like growth factor-II (IGF-II) and growth-hormone releasing hormone (GHRH). In the absence of gross morphological changes, retinoic acid reduced the growth rate without major change of IGF-II mRNA expression, while alpha-difluoromethylornithine produced a complete growth arrest and a sharp decrease of IGF-II mRNA expression. Both reagents increased the expression of GHRH mRNA. Also in this glioblastoma cell line, like other neuroectodermal tumours, IGF-II mRNA is expressed independently from GHRH and seems to be parallel to growth rate. PMID- 1436710 TI - Sexual differences and seasonal variations in vasoactive intestinal peptide immunoreactivity in the suprachiasmatic nucleus of jerboa (Jaculus orientalis). AB - The sexual differences and the seasonal variation in the vasoactive intestinal peptide (VIP) content of the suprachiasmatic nucleus (SCN) of a desert rodent, the jerboa (Jaculus orientalis) were studied using immunocytochemical techniques. During the period of sexual activity (spring-early summer), the VIP immunoreactivity in the SCN was higher in females than in males. In the period of sexual quiescence (autumn), both males and females exhibited an even more intense VIP immunoreaction in the SCN as compared to spring. However, during this period, the sex-related differences in the VIP content of the SCN observed in spring were no longer detectable. The direct possible influence of sex hormones on the VIP content in the SCN, and the physiological significance of the seasonal variation observed in the VIP immunoreactivity in the SCN in this species remains to be determined. PMID- 1436711 TI - Characterization of amyloid fibril protein from a case of cerebral amyloid angiopathy showing immunohistochemical reactivity for both beta protein and cystatin C. AB - We isolated and carried out a chemical analysis of the amyloid fibril protein from the leptomeningeal vessels of a case with non-hereditary cerebral amyloid angiopathy (CAA) showing dual immunohistochemical reactivity with antibodies to both beta-protein and cystatin C. A crude amyloid fibril fraction reacted only with anti-beta-protein antibody, and cystatin C immunoreactivity was observed in the first PBS supernatant. Complete amino acid sequence of this cystatin C immunoreactive protein showed a homologous structure to that of normal cystatin C. It is concluded that cystatin C is not an intrinsic component of the amyloid fibril in this type of CAA. PMID- 1436712 TI - Secretory pathway of beta/A4 amyloid protein precursor in familial Alzheimer's disease with Val717 to Ile mutation. AB - To determine whether the secretory pathway of beta/A4 amyloid protein precursor (APP) was altered in familial Alzheimer's disease (FAD) with a mutation of Val717 to Ile, cerebrospinal fluid was studied by Western blotting. The ratio of the density of the bands labeled with the antibody against the amino-terminal part of beta/A4 protein to that with the antibody against amino-terminal part of beta/A4 protein to that with the antibody against amino-terminal part of APP was not decreased. The present result suggests that the secretory pathway is not altered by the mutation in such a way that amyloidogenic full-length beta/A4 protein is generated. PMID- 1436713 TI - A novel but non-pathogenic mutation in exon 4 of the human amyloid precursor protein (APP) gene. AB - Mutations in the beta-amyloid precursor protein (APP) gene have been associated with both familial Alzheimer disease (FAD) and with hereditary cerebral haemorrhage. The polymerase chain reaction was used to both amplify and sequence exon 4 of the APP gene from genomic DNA of subjects with FAD and normal control subjects. A novel, rare, conservative DNA sequence variant was discovered at nucleotide 459 of codon 153 (valine) in exon 4 of the APP gene in an affected member of a large FAD pedigree. Segregation studies indicate that this mutation is likely to be non-pathogenic, but must be recognized and discriminated from pathogenic mutations during sequencing studies of the APP gene in patients with FAD. PMID- 1436714 TI - Development of speed of repetitive movements in children is determined by structural changes in corticospinal efferents. AB - This study was aimed to determine the relationship between the maturation of corticospinal efferents, determined by transcranial stimulation of motor cortex, and the development of fastest repetitive voluntary motor activity in children. The development of fastest repetitive voluntary motor activity was assessed for 3 different types of movements including fastest repetitive tapping movements, aiming movements and a pegboard transportation task. These 3 motor activities were chosen as they were different as to their dependence on detailed sensory guidance. Despite these differences the speed of all 3 movements showed a very similar developmental profile, which was matched, however, by the developmental slope of the fastest cortico-motoneuronal efferents. Hence the development of central conduction times determines the speed of repetitive movements in children. In contrast, we could not observe significant effects of repetitive training on speed of these movements. We show for the first time that the development of fastest voluntary movements is a structure-bound phenomenon, being independent from learning. PMID- 1436715 TI - Thyrotropin-releasing hormone analogue and serotonin interact within the dorsal vagal complex to augment gastric acid secretion. AB - The effects of serotonin (5HT) and a thyrotropin-releasing hormone (TRH) analogue, RX77368, on vagal control of gastric acid secretion were studied. Microinjection of RX77368 (0.66 pmol in 10 nl), but not 5HT (8 pmol in 10 nl), into the dorsal vagal complex (DVC) evoked a significant increase in acid output. When the same doses of RX77368 and 5HT were co-injected, the amount of acid secreted was significantly greater than that due to RX77368 alone. Thus, 5HT and the TRH analogue interact within the DVC to enhance vagal stimulation of acid secretion. The study suggests a possible functional significance of raphe TRH/serotonergic tracts projecting to the DVC. PMID- 1436716 TI - The long-acting cholinesterase inhibitor heptyl-physostigmine attenuates the scopolamine-induced learning impairment of rats in a 14-unit T-maze. AB - Heptyl-physostigmine (heptyl-Phy), a new carbamate derivative of physostigmine (Phy), has been assessed for potential clinical value by evaluating its in vitro activity against human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), its duration of in vivo activity against rat plasma AChE, and its effects on attenuating a scopolamine-induced impairment in learning performance of young rats in a 14-unit T-maze. Heptyl-Phy demonstrated potent cholinesterase inhibition, with activity similar to that of Phy against AChE, IC50 values 21.7 +/- 2.0 nM and 27.9 +/- 2.4 nM, respectively, and significantly greater than that of Phy against BChE, IC50 values 5.0 +/- 0.1 nM and 16.0 +/- 2.9 nM, respectively. Heptyl-Phy achieved maximum AChE inhibition of 92.5% at 60 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, heptyl-Phy at 1.0, 1.5, 2.0 or 3.0 mg/kg, or vehicle was administered i.p. to 52 3-month-old male Fischer-344 rats 60 min prior to maze training. Thirty minutes prior to training, each animal received either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg). Only a 2.0 mg/kg dose of heptyl-Phy significantly reduced the number of errors in scopolamine-treated rats. The other doses did not improve any aspect of maze performance. Although the therapeutic window of heptyl-Phy did not appear wide enough for clinical use, the longer duration of action of heptyl-Phy would appear beneficial. PMID- 1436717 TI - L-aspartate-beta-hydroxamate exhibits mixed agonist/antagonist activity at the glutamate metabotropic receptor in rat neonatal cerebrocortial slices. AB - L-aspartate-beta-hydroxamate, a glutamate uptake inhibitor, was investigated for activity at a glutamate metabotropic receptor (mGluR) in neonatal rat cerebral cortical slices. Stimulation of phosphatidylinositol hydrolysis by 100 microM (1S,3R)-ACPD was inhibited only very weakly, to a maximal extent of 28%, L aspartate-beta-hydroxamate did however exhibit agonist activity (EC50 = 760 microM) and, although much less potent than (1S,3R)-ACPD (EC50 = 20 microM), its efficacy was approximately 70% of the latter. These results indicate that, at least in this preparation, offspartate-beta-hydroxamate is of little value as an antagonist at the mGluR receptor. PMID- 1436718 TI - Localization of mRNA for beta-adrenergic receptor kinase in the brain of adult rats. AB - A cDNA encoding rat beta-adrenergic receptor kinase (beta-ARK) was cloned and sequenced. By in situ hybridization histochemistry of adult brain, beta-ARK mRNA was expressed intensely in the cerebellar granule cell layer and moderately in the hippocampal pyramidal cells and dentate granule cells. The neocortex and piriform cortex expressed it moderately to weakly, whereas the thalamus and hypothalamus expressed it weakly to faintly. No significant expression of the mRNA was detected in the caudate-putamen. Weak expression of beta-ARK mRNA was detected in several nuclei of the brainstem and in the spinal gray matter. PMID- 1436719 TI - Neuronal responses of the anterior commissural nucleus to osmotic stimulation and angiotensin II in hypothalamic slices in the rat. AB - The firing rate and pattern of activity of neurons in the anterior commissural nucleus (ACN), which was rich in oxytocin-containing neurons, were studied electrophysiologically in hypothalamic slices. Extracellular recording showed that most ACN neurons exhibited irregular or regular continuous spontaneous unit activity. Other neurons showed short burst patterns of activity or were silent. The majority of ACN neurons were activated by bath application of angiotensin II, and a substantial number of them showed inhibitory or excitatory responses to hypertonic bathing medium. These results indicate that magnocellular neurosecretory neurons in the ACN may participate in the regulation of water balance. PMID- 1436720 TI - Non-independent quantum bumps in Limulus ventral nerve photoreceptors--a new insight in the light transduction mechanism. AB - Single photon-induced transient currents, called quantum bumps were stimulated by short flashes in dark-adapted ventral nerve photoreceptors of Limulus. Flash intensities were set to activate 3 or more bumps. In most cases, current bumps were activated with a constant rate. The frequency of bump occurrence was between 9 and 17 Hz. Results show that consecutive bumps are not independent and that some of them are not activated by a photon. The periodic bump activation indicates a molecular mechanism which quantifies the transmitter release not only by a light quantum, but also by a late phase of the transduction cascade. A model is proposed, in which Ca2+ ions released from intracellular stores transiently block the further Ca2+ release by inositol trisphosphate in an all-or-none manner. PMID- 1436722 TI - Cuts in funding expected for nursing education. PMID- 1436721 TI - Remembrance of things past--present. PMID- 1436723 TI - Ways of teaching, learning, and knowing about violence against women. PMID- 1436724 TI - Substance abuse during pregnancy. Legal & health policy issues. PMID- 1436725 TI - Shortage as shorthand for the crisis in caring. PMID- 1436726 TI - A nursing center in Brooklyn. PMID- 1436727 TI - Revisiting nursing's media image. PMID- 1436728 TI - Sudden infant death syndrome in 1992: the known and unknown. AB - Sudden infant death syndrome (SIDS) continues to be the leading cause of death in infants from one month to one year of age. We present the results to the Fifth Annual Perspectives on SIDS. This program is one component of the educational services of the New Jersey SIDS Resource Center. PMID- 1436729 TI - Sudden infant death syndrome in New Jersey: 1991. AB - Sudden infant death syndrome (SIDS) is the leading cause of death in infants one month to one year of age. The New Jersey Sudden Infant Death Syndrome Resource Center gathers epidemiological data on all SIDS deaths in New Jersey, noting differences in population and countries. PMID- 1436730 TI - Medium chain acyl-coenzyme A dehydrogenase deficiency. AB - Medium chain acyl-coenzyme A dehydrogenase deficiency (MCADD) was the first metabolic disorder found to be associated with sudden infant death syndrome. This review covers recent advances in the biochemical and molecular understanding of MCADD. PMID- 1436731 TI - Sudden infant death syndrome: loss and bereavement. AB - Clinical perspectives of sudden infant death syndrome (SIDS) and family responses to loss and bereavement are addressed. The author discusses factors such as family stage, parental dyad issues, and the needs of young children, friends, and caregivers. PMID- 1436732 TI - Sudden infant death syndrome and subsequent siblings. AB - Studies indicate that at least 98 (SIDS) in subsequent siblings, summarizes the results of percent of all subsequent SIDS siblings will have a normal outcome. While the data regarding a single SIDS occurrence can be viewed as encouraging, 2 percent mortality is not trivial. Parents of SIDS siblings are in need of appropriate counseling and support. In the unfortunate case of subsequent sibling SIDS deaths, the mortality rate may be as high as 18 percent. Regretably, all attempts at prospective identification of infants destined to die of SIDS have proved futile. The development of a prospective screening test has been hindered by insufficient understanding of the specific cause or causes of SIDS. Attention, thus, has been directed at the development of effective home intervention. Cardiorespiratory monitoring has been identified as one means of home intervention, and a comprehensive support program has resulted in the successful home monitoring of many infants at high risk for SIDS. Studies aimed at making prospective identification a clinical reality continue. Accordingly, we must persist in our efforts to provide support to parents who have experienced one of life's worst tragedies. PMID- 1436733 TI - Neurodevelopmental outcome in infants with apnea. AB - The neurodevelopmental outcome of term infants with acute life-threatening events (ALTE) and preterm infants with persistent apnea of prematurity were compared to matched control populations. No differences in developmental outcomes were seen between the study and control populations. PMID- 1436734 TI - NJ SIDS Resource Center: program for bereaved families. AB - The New Jersey Sudden Infant Death Syndrome Resource Center counsels approximately 120 bereaved families each year, conducts l medical and community education programs, and manages the sudden infant death syndrome database for New Jersey. PMID- 1436735 TI - Sudden infant death syndrome: an overview. AB - The diagnosis of sudden infant death syndrome (SIDS) depends on a thorough and complete autopsy. Many of the infants who die of SIDS have common findings. There are certain steps to be taken for prevention and diagnosis of SIDS. Further investigation of this syndrome still is necessary. PMID- 1436736 TI - Intracellular steps of bacterial cell wall peptidoglycan biosynthesis: enzymology, antibiotics, and antibiotic resistance. PMID- 1436737 TI - Natural sesquiterpenoids. PMID- 1436738 TI - Clerodane diterpenoids. PMID- 1436740 TI - Transformational leadership. PMID- 1436739 TI - Biosynthesis of polyketide metabolites. PMID- 1436741 TI - Transformational leadership. PMID- 1436742 TI - Stimulate the interest of professional nurses in cultural diversity in this global community. PMID- 1436743 TI - Structures, strategies, and synthesis: the nurse executive as social architect. PMID- 1436744 TI - Transformational leadership in an age of chaos. PMID- 1436745 TI - Educational experiences of transformational nurse leaders. PMID- 1436746 TI - Friends of nursing: a strategy for transforming the community-nursing relationship. PMID- 1436747 TI - Transformational leadership in action: an interview with a health care executive. Interview by Gloria E. Bader. PMID- 1436748 TI - Professional practice partnerships: a new approach to creating high performance nursing organizations. PMID- 1436749 TI - Shared governance: the leadership challenge. PMID- 1436750 TI - Leadership strategies for organizational change: applications in community nursing centers. PMID- 1436751 TI - Using cooperative decision-making strategies in nursing practice. PMID- 1436752 TI - Characteristics of nurse managers in community and metropolitan teaching hospitals: a comparative study. PMID- 1436753 TI - High dose refractoriness to the neuromuscular toxicity of dithiobiuret in rats. AB - Increasing the daily dose of dithiobiuret (DTB) given to rats from 0.5 to 1 to 5 mg/kg shortened the latency to onset of treadmill failure and associated flaccid muscle tone from 7 to 5 to 3 days, respectively. Death generally did not follow treadmill failure for at least 2-3 days. After 3 consecutive days of treatment with 5 mg/kg, gastrocnemius muscle contractions elicited by high frequency trains of nerve stimulation were lower in peak tension and more susceptible to tetanic fade (rapid tension decline in tetanus) than were contractions from control rats. Conversely, rats given 12 mg/kg of DTB for 3 days did not exhibit treadmill failure, flaccid skeletal muscle tone, or tetanic contractile abnormalities. Additional treatment with this dose for 2-3 days was required to produce treadmill failure which was not accompanied by flaccid muscle tone. Refractoriness to development of toxicity with DTB was limited in its spectrum; decreased feed and water intake, weight loss, diuresis, dehydration, chromodacryorrhea, and production of mucoid feces occurred even in the absence of flaccid muscle tone. Tissue distribution of DTB-derived [14C] determined 3 hr after injection of [14C]-DTB (12 mg/kg) was largely unaffected by prior treatment with unlabeled DTB (12 mg/kg/day x 2 days). Conventional microelectrode recording studies using end-plates of extensor digitorum longus muscles indicated that abnormalities occurred in quantal release of acetylcholine (ACh) after 5mg/kg/day but not 12 mg/kg/day of DTB. Specifically, reduced quantal content, increased amplitude and prolonged decay of miniature end-plate potentials were observed. The mechanism by which large daily doses overcome or prevent the expected development of flaccid muscle tone and depressed release of ACh typically associated with treatment with DTB does not involve compensatory increases in quantal release of ACh, or altered distribution of the compound. PMID- 1436754 TI - Delayed neurotoxicity of trixylenyl phosphate and a trialkyl/aryl phosphate mixture, and the modulating effect of atropine on tri-o-tolyl phosphate-induced neurotoxicity. AB - Two hydraulic fluids, Fyrquel EHC (trixylenyl phosphate) and Reofos 65 (trialkyl/aryl phosphate mixture), were examined for effects of organophosphorus induced delayed neurotoxicity (OPIDN) in hens using the OECD Test Guideline (1984). Furthermore, the influence of atropine and the concentration of tri-o tolyl phosphate (TOTP) in the oil vehicle on the development of OPIDN were investigated. For Fyrquel EHC a neurotoxic effect was demonstrated with single oral doses of 5, 10 and 15 g/kg. Reofos 65 caused no clinical neurotoxic effect after single oral doses of 5, 10 and 15 g/kg. Redosing at day 22 with Reofos 65 did not result in clinical delayed neurotoxicity, but minor histopathological changes were found in the spinal cord and peripheral nerves. Atropine 10 mg/kg im delayed the onset of OPIDN caused by TOTP 1 g/kg po without affecting the final neurotoxic effect. Dilution of TOTP in large amounts of soybean oil vehicle reduced its neurotoxic effect. In conclusion, the neurotoxic potential of the hydraulic fluids was very low. The effect of atropine and the concentration of the test compound in oil vehicle should be taken into consideration when designing experiments on OPIDN. PMID- 1436755 TI - Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals. AB - The serine/cysteine hydrolase inhibitor phenylmethylsulfonyl fluoride (PMSF) markedly intensifies the clinical expression of organophosphorus-induced delayed neurotoxicity (OPIDN) in adult chickens when administered after organophosphate exposure. In this study, we have examined the ability of PMSF post-treatment to affect sensitivity to OPIDN in developing animals at ages normally showing resistance. Chickens (35, 49 or 70 days of age) were treated with diisopropylphosphorofluoridate (DFP, 2 mg/kg, sc) and then treated four hours later with PMSF (90 mg/kg, sc) or vehicle only and examined for clinical signs of ataxia and incoordination. Chickens treated with DFP alone showed a marked age related increase in the severity of motor deficits. Birds treated with DFP followed by PMSF showed more extensive clinical deficits relative to those treated with DFP only, but relatively similar degrees of motor dysfunction among the age groups. Cervical spinal cord samples processed by the Fink-Heimer degeneration method indicated that PMSF post-treatment induced more extensive axonal degeneration in all age groups relative to treatment with DFP only. As the DFP treatment alone caused greater than or equal to 90% inhibition of neurotoxic esterase activity (NTE, the putative molecular target site for OPIDN), interaction with NTE by PMSF does not appear to be involved in potentiation. We hypothesize that PMSF potentiates OPIDN through impairment of a physiological process which normally imparts resistance to young animals and which regresses during development. PMID- 1436756 TI - Functional/metabolic modulation of the brain stem lesions caused by 1,3 dinitrobenzene in the rat. AB - To determine whether neuronal activity plays a role in the localisation of brain stem lesions in 1,3-dinitrobenzene intoxication we produced asymmetrical changes in auditory input by rupturing the left tympanic membrane in Fischer rats. This raised the auditory threshold on that side from 57-63 dB to 104-122 dB. It also decreased glucose utilisation in the ipsilateral cochlear nucleus and significantly increased utilisation in the contralateral nucleus, resulting in a relative deficit of 72 +/- 6%. Similarly, tympanic membrane rupture led to decreased glucose utilisation in the contralateral and increased utilisation in the ipsilateral inferior colliculus. Additional exposure to "white noise" prevented the decrease in glucose utilisation in the contralateral inferior colliculus. Dosing with dinitrobenzene (10 mg/kg in 4 doses over 48 hr) to otherwise normal rats produces symmetrical vasculonecrotic lesions in these regions, but in animals with left tympanic membrane rupture the severity of morphological changes in the ipsilateral cochlear nucleus and the contralateral inferior colliculus were substantially reduced. Additional exposure to "white noise" increased the degree of damage in the ipsilateral cochlear nucleus and contralateral inferior colliculus. These findings indicate that altered auditory function in rats, with its associated metabolic consequences exercises a significant role in the development of brain stem damage in auditory pathways following dinitrobenzene intoxication. PMID- 1436757 TI - Mitochondrial glutathione and methyl iodide-induced neurotoxicity in primary neural cell cultures. AB - The status of both cytosolic and mitochondrial glutathione was studied in primary cultured cerebrocortical cells from fetal mice using the selective membrane solubilizing properties of digitonin and after exposure to the monohalomethane methyl iodide. A correlation was found between cell injury (assessed by lactate dehydrogenase leakage 24 hr after exposure) and early loss of mitochondrial glutathione (2 hr after exposure), while cell death did not appear directly dependent on cytosolic glutathione depletion. The antioxidants BW 755C (3-amino-1 [m-(trifluoromethyl)phenyl]-2-pyrazoline) and DPPD (N,N'-diphenyl-p phenylenediamine), and the glutathione precursor N-acetyl-L-cysteine were used to modify cellular responses to methyl iodide. Prevention of cell injury by these reagents was obtained only under conditions where at least 50% of the normal level of mitochondrial glutathione was preserved after methyl iodide exposure. Mitochondrial metabolic activity (reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide, MTT) was affected by exposure to methyl iodide and correlated with mitochondrial glutathione depletion and cytotoxicity. These findings indicate that the mitochondrial glutathione pool and mitochondrial functions may be the most significant intracellular targets of methyl iodide in neural cultures. Moreover, the present work exemplifies the dependence of neural cell viability on the status of mitochondrial functions and suggests that, as in the liver, mitochondrial glutathione is an important component of cellular homeostasis in nervous tissue. PMID- 1436758 TI - Corticosterone hypersecretion in preweanling rats exposed neonatally to trimethyltin. AB - Developmental neurotoxicity may be influenced by effects of a compound on endocrine function. Here we report that developmental exposure to TMT increases the corticosterone (CS) response to stress in developing rat pups. Long-Evans rat pups were injected i.p. with either 6 mg/kg TMT hydroxide (in 10 microliters/g BW NaCl) or vehicle on Postnatal Day 5 (PND5) or 10 and were then tested for their CS response to restraint stress on PND12, 16, or 20. In the stress test, pups were maternally deprived in individual compartments of an incubator for 24 hr, and then blood sampled by decapitation either immediately (basal), or 30, 60 or 90 min after the onset of a 15-min period of restraint in a wire-mesh holder. Regardless of TMT exposure or age of testing, this procedure produced a peak in plasma CS at 30 min which then recovered to basal levels by 90 min. TMT exposure on PND5 (Experiment 1) resulted in CS hypersecretion relative to vehicle-injected controls on PND12 and 16 but not PND20. TMT exposure on PND10 (Experiment 2) had no effect at PND12 but elevated CS over vehicle controls at PND16 and 20. PND15 exposure to TMT resulted in CS hypersecretion in pups tested on PND20. Neonatal organotin exposure appears to alter CS secretion in a manner that is influenced by age of exposure and age of testing. PMID- 1436759 TI - Effects of trimethyltin on repeated acquisition (learning) in the radial-arm maze. AB - Trimethyltin (TMT) was used as a positive control neurotoxicant to evaluate a repeated acquisition procedure for the 8-arm radial maze. Ten male Long-Evans rats were trained to collect a single food pellet at the end of each baited arm on each trial of a daily 12-trial test session. Four of the eight arms were baited on all trials of a given session. The set of four baited arms was changed each day: thus the rats were required to learn a new set of baited arms in each session. In trained rats, error frequencies (entries into unbaited arms) declined from about 4 on Trial 1 to less than 1 on Trials 4-12 in each session: this within-session error reduction thus defined an acquisition baseline which was evaluated for its sensitivity to TMT. Learning was impaired after 7 mg/kg (iv) TMT, as shown by a slower decline in within-session error frequencies in all treated rats. Errors and response times were elevated for 5 weeks after TMT but returned to control levels thereafter. Histological examination of hippocampi showed damage in all treated rats 18 weeks after treatment; however, no significant relationship between degree of damage and behavioral effect was observed. Analysis of errors showed that TMT more strongly impaired the rats' ability to avoid arms in the current unbaited set than those baited arms already entered on a given trial (i.e., working memory). These dissociations between behavior and hippocampal morphology in terms of time course, magnitude of effect across animals, and error type suggest that performance of this task does not depend upon hippocampal integrity, as do other tasks involving spatial working memory. Recovery of function in this kind of task may shed light on processes of neural plasticity after exposure to neurotoxic compounds. PMID- 1436760 TI - Effects of pre- plus postnatal exposure to methylmercury in the monkey on fixed interval and discrimination reversal performance. AB - Female monkeys were dosed with 0, 10, 25 or 50 micrograms/kg/day of mercury as methylmercuric chloride. When blood levels reached equilibrium, females were bred to untreated males. A total of 5, 1, 2, and 5 live infants were born in the four dose groups, respectively. Infants were separated from their mothers at birth, and dosed with the same dose their mothers had received. Maternal blood mercury levels averaged 0.33, 0.78, or 1.41 ppm for the three dosed groups respectively. Infant blood mercury levels averaged 0.46, 0.93, or 2.66 ppm at birth, and decreased slowly to steady state levels of 0.20, 0.25, or 0.60 ppm. Behavior was assessed during infancy on a nonspatial discrimination reversal task and fixed interval performance, and when monkeys were juveniles on a series of nonspatial discrimination reversal tasks. During infancy monkeys were tested 7 days per week, 16-21 hr per day in a home-cage environment. As juveniles, they were tested five days per week in a standard operant test environment. For the discrimination reversal tasks, there were no strong indications of differences between treated and control monkeys either as infants or juveniles. Treated monkeys tended to perform transiently better than controls when first introduced to the task both as infants and juveniles. On the Fl, treated monkeys received more reinforcements, and had shorter pauses and lower quarter-life values than control monkeys. Analysis of feeding behavior over the session during infancy revealed marginally longer periods of feeding in methylmercury-treated infants. These results suggest that pre-plus postnatal exposure to methylmercury did not result in gross intellectual impairment in these monkeys, but may have interfered with temporal discrimination. PMID- 1436761 TI - Effects of complexed iron and aluminium on brain calcium. AB - Ferric lactate increases Ca(2+)-uptake by Ehrlich carcinoma ascites cells as well as in vitro and in vivo Ca(2+)-uptake by the liver. Iron and aluminium are increased in the substantia nigra of patients with Parkinson's disease and aluminium is suspected to be involved in the pathophysiology of Alzheimer's disease. This study was conducted to determine if there is any relationship between iron and aluminium uptake and a possible calcium influx into brain tissue. Groups of Swiss mice were injected in the tail vein with 100 microliters of 0.05 M ferric lactate plus 2 microCi45CaCl2, or 100 microliters of 0.05 M aluminium lactate plus 2 microCi45CaCl2, or 100 microliters of saline plus 2 microCi45CaCl2. Twenty-four hr later they were sacrificed by decapitation. Samples of blood and the total brain were weighed and ashed. The ashes were dissolved and the solution transferred to counting vials evaporated to dryness. A scintillation solution was added to the vials and the radioactivity was counted. To accurately assess brain uptake in each animal the value of brain specific activity was related to blood specific activity. When compared to those of control animals, these values gave the 24 hr increase of 45Ca-uptake by brain of ferric lactate or aluminium lactate-treated animals. A significant increase of 45Ca-uptake was observed for ferric lactate (136% of control value, p less than 0.005), which is more important for aluminium lactate (163% of control value, p less than 0.001). The nature of the complexed metal-brain tissue interaction is not known, several mechanisms are discussed. PMID- 1436762 TI - New dimensions of lead neurotoxicity, redefining mechanisms and effects. 9th International Neurotoxicology Conference. Little Rock, Arkansas, October 28-31, 1991. Abstracts. PMID- 1436763 TI - The influence of dietary fat on food intake and body weight. AB - Excessive intake of dietary fat is associated with a number of nutrition-related disorders, including obesity, heart disease, and cancer. The over-consumption of fat may be related to its palatability, high energy density, or physiological effects. This article reviews possible reasons why fat intake is high, examines the relationship between diet composition and body weight, and explores potential fat reduction strategies. It is concluded that low-fat or fat-free products could be useful in reducing the percentage of calories derived from fat, although this assertion needs to be further tested in controlled laboratory experiments and validated on a population basis. PMID- 1436764 TI - Low serum retinol is associated with increased severity of measles in New York City children. AB - Children with no known prior vitamin A deficiency exhibited a significant decline in their serum retinol levels during the acute phase of measles. This decline in circulating retinol was associated with increased duration of fever, higher hospitalization rates, and decreased antibody titers. PMID- 1436765 TI - What is the physiological origin of free D-amino acids in mammals? AB - A previously unknown metabolite of vitamin B6, tentatively identified as adenosine-N6-diethylthioether-N1-pyridoximine-5'-phosphate, accounts for up to 30% of the total intracellular vitamin B6 observed in tumor cells cultured in the presence of radiolabeled pyridoxine. When various animal and human tumor cells were incubated with radiolabeled pyridoxine, the formation of this metabolite was greatest in rapidly growing cells that were the least differentiated. If analytical methods are verified, the presence of the compound in serum may provide an indicator of in vivo tumor growth. PMID- 1436766 TI - A novel vitamin B6 metabolite may be a circulating marker of cancer. AB - A previously unknown metabolite of vitamin B6, tentatively identified as adenosine-N6-diethylthioether-N1-pyridoximine-5'- phosphate, accounts for up to 30% of the total intracellular vitamin B6 observed in tumor cells cultured in the presence of radiolabeled pyridoxine. When various animal and human tumor cells were incubated with radiolabeled pyridoxine, the formation of this metabolite was greatest in rapidly growing cells that were the least differentiated. If analytical methods are verified, the presence of the compound in serum may provide an indicator of in vivo tumor growth. PMID- 1436767 TI - Could food labels be dangerous to health? PMID- 1436768 TI - Cooperative relationships between professional societies and the food industry: opportunities or problems? AB - A variety of cooperative relationships may potentially exist between professional or voluntary organizations and food companies: endorsements of food products, health messages, or educational and informational materials; certification of nutrient components of food products that meet a certain standard of a society; and acceptance of food advertising in society publications and the display of food products at society meetings. We queried the American Heart Association, the Society for Nutrition Education, the American Cancer Society, the American Diabetes Association, and the American Dietetic Association about past and present policies on these various relationships. Specific examples of cooperative relationships are discussed, weighing risks and benefits to the food company, the professional or voluntary organization, and the public. Guidelines are suggested for professional societies in evaluating different cooperative relationships, with the public's health and nutritional well-being as the primary consideration. PMID- 1436769 TI - Enterostatin: the pancreatic procolipase activation peptide--a signal for regulation of fat intake. PMID- 1436770 TI - Food irradiation. PMID- 1436771 TI - Alcohol abuse not a proven risk factor for violent behavior. PMID- 1436772 TI - Nursing protocol on domestic violence. PMID- 1436773 TI - Taking the "cef" out of cephalosporins. PMID- 1436774 TI - A case study of radiation-induced coronary disease. PMID- 1436775 TI - NP unity and minimum education requirements promote credibility. PMID- 1436776 TI - HIV-infected pregnant women and their infants. Primary health care implications. AB - Human immunodeficiency virus infection in women and infants is a significant and growing health care problem in the United States. Young adult black or Hispanic women are at particular risk, especially if they use intravenous drugs or are the sexual partner of someone who does. However, acquired immunodeficiency syndrome/HIV infection is a significant cause of mortality in women of reproductive age (i.e., 15 to 44 years). In addition, the incidence of AIDS in infants directly correlates to the incidence of AIDS in childbearing women. HIV infected pregnant women need on-going comprehensive prenatal care with a special focus on HIV management. Antepartum care should include an HIV-focused history and physical examination, as well as additional laboratory assessments to screen for viral and bacterial infections. Intrapartum care should focus on avoiding contact with infected or potentially infected secretions and body fluids. Postpartum care should emphasize development of a comprehensive and integrative plan of care for mother, baby and family unit prior to discharge. Avoidance of breastfeeding and strategies to prevent further HIV transmission must be stressed. PMID- 1436777 TI - A guide to primary care of iron-deficiency anemia. AB - Iron deficiency, the most common cause of anemia, is prevalent in 10 percent to 30 percent of the world's population. Inadequate intake of iron may be an important causative factor, particularly when the body requires more iron than usual (e.g., during infancy, early childhood, adolescence, pregnancy and periods of blood loss). The popular increase of fiber in diets may increase the incidence of iron-deficiency anemia because too much fiber in the diet renders available iron unabsorbable. Symptoms in children include skin or conjunctival pallor, excessive sleepiness, learning disabilities, diminished attention span, tiredness, irritability or inappropriate behavior, and pica. Adults may have shortness of breath, decrease in exercise tolerance, palpitations, tachycardia, angina, congestive heart failure, orthopnea and edema. Iron deficiency occurs in sequential states and is measured by many laboratory tests. The levels of hemoglobin and hematocrit are both decreased, while the red blood cell count may be normal initially, but will decrease as the iron-deficiency state continues. The steps of treatment include correction of the underlying disorder, administration of the amount of iron needed and observation of the response to treatment. PMID- 1436778 TI - Caring for the patient in pain, Part II. PMID- 1436779 TI - Coaching nurses effectively. PMID- 1436780 TI - How to take multiple-choice tests. PMID- 1436782 TI - The costume party. PMID- 1436781 TI - Going for your goals. PMID- 1436783 TI - Filling out an incident report. PMID- 1436784 TI - Should you be tested for H.I.V.? PMID- 1436785 TI - Interpreting white blood cell counts. PMID- 1436786 TI - Removing an esophageal obturator airway. PMID- 1436788 TI - Chemotherapy certification. PMID- 1436787 TI - Helping your patient cope with mitral valve prolapse syndrome. PMID- 1436789 TI - Extra tip for discharge planning. PMID- 1436790 TI - Assessing complications of P.T.C.A. PMID- 1436791 TI - Close-up on Colles' fracture. PMID- 1436792 TI - Do you know the value of a non narcotic? PMID- 1436793 TI - Mr. Webb had a few reasonable requests .... PMID- 1436794 TI - P.I.C.C. & M.L.C. lines. Options worth exploring. PMID- 1436795 TI - Would you divulge confidential information about a patient's H.I.V. status? PMID- 1436796 TI - Comfort and companionship. PMID- 1436797 TI - Tom was a big challenge. PMID- 1436798 TI - Tips on teaching the elderly. PMID- 1436799 TI - Helping your patient overcome loneliness. PMID- 1436801 TI - The many faces of room E-212. PMID- 1436800 TI - Using a stationary walker. PMID- 1436802 TI - Keeping the faith. PMID- 1436803 TI - Guarding against aspiration pneumonia. PMID- 1436804 TI - Clotrimazole for vaginal yeast infections. PMID- 1436805 TI - Abstracts of the 16th annual meeting of the Japan Neuroscience Society. Osaka, Japan, December 8-10, 1992. PMID- 1436806 TI - The immunization crisis in New York. PMID- 1436807 TI - Transesophageal echo: defining the indications. PMID- 1436808 TI - Esophageal perforation. PMID- 1436810 TI - Extracranial carotid arterial disease: a prognostic factor for atherothrombotic brain infarction and cerebral transient ischemic attack. AB - A prospective study investigated the prevalence of extracranial carotid arterial disease by carotid duplex ultrasonography, and evaluated its correlation with the incidence of atherothrombotic brain infarction or cerebral transient ischemic attack in 949 patients, mean age 82 +/- 8 years. The mean follow-up period was 45 months. Of 949 patients, 37 (4%) had 80%-100% extracranial carotid disease (mean follow-up, 24 +/- 15 months), 113 (12%) had 40%-80% extracranial carotid disease (40 +/- 19 months follow-up), and 799 (84%) had 0%-40% extracranial carotid disease (47 +/- 14 months follow-up). The average annual incidence of atherothrombotic brain infarction was 37% in patients with 80%-100% extracranial carotid disease, 9% in patients with 40%-80% extracranial carotid disease, and 4% in patients with 0%-40% extracranial carotid disease. The average annual incidence of transient ischemic attack was 3% in patients with 80%-100% extracranial carotid disease, 2% in patients with 40%-80% extracranial carotid disease, and 1% in patients with 0%-40% extracranial carotid disease. The Cox proportional hazard model showed that among the variables evaluated, the severity of extracranial carotid disease correlated with the highest relative risk of developing atherothrombotic brain infarction (2.5x higher relative risk) or transient ischemic attack (2.8x higher relative risk). Patients with an earlier atherothrombotic brain infarction had a 2.1x higher probability of developing atherothrombotic brain infarction and a 1.9x higher chance of developing transient ischemic attack than those without an earlier atherothrombotic brain infarction. Age was a prognostic variable for new atherothrombotic brain infarction, and male sex was a prognostic variable for new transient ischemic attack. PMID- 1436809 TI - Pap smear histories in a medical clinic: accuracy of patients' self-reports. AB - Women using the medical clinic of a public hospital were interviewed about their Pap smear histories to assess the accuracy of self-reported smears and to identify groups in need of further screening. Interview data from 263 women were compared with cytology files and hospital records. In spite of considerable agreement between patient report and record, patients reported significantly more recent smears than were documented. Accuracy of recall was not dependent on age or birthplace, but on the length of time since the last smear. About half the women had been screened within the past two years, whereas one tenth had never been screened. Women aged 65 years or older had fewer recent smears than younger women, while foreign born women were more likely never to have had a Pap smear than were United States born women. We conclude that self-reported information is useful in assessing Pap smear histories, but the screening rates that result should be treated as high estimates. Significant opportunities for screening exist in ambulatory care sites in low-income communities. PMID- 1436811 TI - AIDS prevention by needle exchange. PMID- 1436812 TI - The experience of an American medical student with an aboriginal community in central Australia. PMID- 1436813 TI - Leonardo da Vinci's anatomical drawings. PMID- 1436814 TI - The story of Lassa fever. Part III: The disease in the community. PMID- 1436816 TI - Cervical esophageal perforation--a unique presentation. PMID- 1436815 TI - Acute tricuspid valve incompetence secondary to blunt trauma [see comment]. PMID- 1436817 TI - Diltiazem-induced myoclonus. PMID- 1436818 TI - The changing winds. PMID- 1436819 TI - The role of third party payors in medical care. PMID- 1436820 TI - Pseudoleukemia in a patient with Hodgkin's disease. PMID- 1436821 TI - [Request for inquiry into the competence of a nurse]. PMID- 1436822 TI - [Prenatal diagnosis. Better understanding for better performance]. PMID- 1436823 TI - [A baccalaureate program conceived for nurses]. PMID- 1436824 TI - [On the topic of midwives--where do we stand?]. PMID- 1436825 TI - [The feminist approach and nursing science--a promising alliance]. PMID- 1436826 TI - From hospital to community: a follow up of community placement of the long term mentally ill. AB - AIM: To evaluate the planned movement of long stay patients with chronic mental disorders from Sunnyside Hospital into staffed residential accommodation in the community. METHOD: Sixty-nine long stay psychiatric patients were followed up over 18 months to assess their social functioning, psychiatric symptomatology, resource use, relapse rate, satisfaction with their care, and impact on the community. RESULTS: Social functioning and psychiatric symptomatology scores on the social behaviour schedule remained stable overall. Relapse rates were low, and rehospitalisation rare. Use of community and area health board resources tended to decrease. Over 90% of patient responses indicated satisfaction with their new living arrangements. Over 50% reported no contact with outside friends, though over the follow up period about 70% maintained at least monthly contact with relatives. CONCLUSION: Careful community placement of the long term mentally ill, with ongoing supervision, can have a successful outcome from clinical, patient and community perspectives. PMID- 1436827 TI - Nutritional hassles. PMID- 1436828 TI - Consensus on acute asthma management in children. Ad Hoc Paediatric Group. PMID- 1436829 TI - The quality of a laboratory test in general practice: the throat swab example. AB - AIM: To measure the repeatability, the flow of information, and the data entry error of the throat swab test from a suburban general practice. METHOD: A prospective study of consecutive patients seen in routine consultation for a sore throat as their primary complaint. Repeated throat swabs were taken for each patient. Carbon copies of routine laboratory forms were collected. RESULTS: The kappa statistic for reproducibility of the throat swab test was 0.63 (95% CI 0.50 0.77). In 5.8% of patients, one swab was positive and the other negative. Information took one day or less to travel to and from the laboratory for 25.7% of patients with a beta-haemolytic streptococcal growth compared to the 9.9% of patients with no growth (chi 2 = 6.17, p < 0.02). The laboratory received 53% of the swabs on the day they were taken. Delays in getting the swabs to the laboratory occurred when swabs were taken in the afternoon session or on weekends. Monday morning gave the quickest return. Data entry errors were found on 15.9% of patient forms. CONCLUSION: The quality of the throat swab test needs improvement in the suburban general practice context. PMID- 1436830 TI - Clozapine protocol: a collective approach to use of an unregistered medicine. AB - We describe a protocol for the use of an unregistered antipsychotic medicine, clozapine, in a mental health service. Traditionally, prescribing of unregistered medicines has been a matter between prescriber and patient alone. However, clozapine carries a high risk of agranulocytosis and its use requires strict adherence to monitoring procedures. Persons most likely to benefit from it include many who, because of their psychosis, may be unable to give truly informed consent or to react appropriately to adverse reactions. We have designed a protocol which seeks to ensure that this medicine is given only to those whose severity of illness and lack of response to all other reasonable treatment outweighs the risk of agranulocytosis, that it is used with maximum safety and that only persons who have been shown to benefit from the medicine continue to receive it after an initial trial. Although this protocol has been accepted by the medical staff, questions of clinical autonomy and liability in the event of medical misadventure remain. PMID- 1436831 TI - Adult measles in Auckland Hospital, 1991. PMID- 1436832 TI - Venesection responsive cardiomyopathy in a patient with idiopathic haemochromatosis. PMID- 1436833 TI - The portable hyperbaric chamber for the treatment of high altitude illness. PMID- 1436834 TI - Vitamin K administration in the newborn: statement by Fetus and Newborn Committee of Paediatric Society of New Zealand. PMID- 1436835 TI - National Women's and Cherry Farm Hospitals. PMID- 1436836 TI - Fenoterol: enough is enough. PMID- 1436837 TI - Ondansetron antiemetic therapy for chemotherapy and radiotherapy induced vomiting in children. AB - AIM: To evaluate ondansetron as the sole antiemetic in children treated with emetogenic chemotherapy and irradiation. METHODS: Fifteen children aged 3-11 years were studied. Seven had acute lymphoblastic leukaemia, two acute myeloid leukaemia, two lymphoma and four had other tumours. Ondansetron 5 mg/m2 IV or 4 mg by mouth was given immediately before chemotherapy or radiation treatment and continued eight hourly for 24 hours. Nausea and vomiting was assessed during treatment and for the next 48 hours, and graded using WHO criteria. RESULTS: Thirty-eight courses of chemotherapy were assessed, 27 severely emetogenic and 11 moderately emetogenic. Two included total body irradiation. The most severe nausea and vomiting was grade 2 (transient vomiting) reported in six children. Nausea and vomiting was abolished on subsequent courses in four of these children by increasing the ondansetron dose frequency to six hourly. The remaining children experienced no nausea or vomiting (n = 7) or only nausea (n = 2). Nausea and vomiting were each completely controlled in 27 courses. CONCLUSIONS: Ondansetron is a cost effective and safe antiemetic in children receiving chemotherapy and total body irradiation, minimises weight loss on treatment and enables outpatient chemotherapy in some cases. PMID- 1436838 TI - Residential care for the long term mentally ill in Canterbury: options, costs and funding sources. AB - AIMS: To obtain estimates of the costs of the main options of care for the long term mentally ill and to compare different approaches to costing. METHOD: Resources used by samples of residents in extended hospital care (EC, n = 43), community staffed houses (SH, n = 30), boarding houses (BH, n = 43) and group homes (GH, n = 100) were identified and costed using both the expenditure and total resource concepts of cost estimation. RESULTS: Using the expenditure concept of cost SH was the most expensive at $773 per person per week, compared to $700 for EC, $189 for BH and $155 for GH. Using the resource cost approach, valuing all resources used, SH and EC were similar at $790, compared to $184 and $169 for BH and GH care. Nursing was the most costly input with striking differences between nursing costs in the four modes of care. CONCLUSIONS: The results indicate a gap in the spectrum of residential care options, between high and low cost care. Future funding arrangements will require improved linkage between needs assessment and resource provision. PMID- 1436839 TI - The Cancer Registry: 1991 review report and recent progress. PMID- 1436840 TI - Viral hepatitis in the Christchurch community. AB - AIM: To determine the relative frequency of known causes of viral hepatitis in the Christchurch community. METHODS: Serum samples were collected at a private laboratory from patients aged 15-75 years who had an elevated transaminase of at least twice normal. RESULTS: One hundred and thirty-three subjects entered the study of whom 32 were positive for Epstein Barr virus, three for cytomegalovirus, nine for hepatitis A virus, and eight for hepatitis B virus. Paired convalescent samples were obtained from 64 of the remaining 81 subjects (17 lost or declined) and seven of these were positive for hepatitis C. Assuming a similar percentage in the lost/declined group this corrects to nine. CONCLUSION: The relative frequency of viral agents causing hepatitis was Epstein Barr virus 52%, cytomegalovirus 5%, hepatitis A virus 15%, hepatitis B virus 13% and hepatitis C virus 15%. Hepatitis C virus is a common cause of viral hepatitis in the Christchurch community. PMID- 1436841 TI - Immunisation status of children in the eastern Bay of Plenty. AB - AIM: To assess the status of immunisation of children in the eastern Bay of Plenty. METHOD: Survey of general practitioner records and case notes of all resident children born over a period of two years and aged from five to 29 months. Immunisation was considered up to date if received within a reasonable period of the expected time. RESULTS: One thousand five hundred and ninety-three children were studied (97% of those known to be resident). The six week immunisations were received by 91%, 88% received the three month, and 81% the five month vaccines. Delivery of second year immunisation was much less successful, only 72% receiving measles or MMR vaccine despite publicity about a current measles epidemic and 61% the eighteen month vaccines. CONCLUSION: Forty three percent children of two years of age had not received the full recommended immunisation schedule. Some of the contributing factors were identified and measures that could improve immunisation uptake are discussed. PMID- 1436842 TI - The effect of emergency department policy change on Hutt district general practices. AB - AIM: To determine the impact of the new Hutt Hospital emergency care policy as perceived by general practitioners and measure the level of general practitioner emergency services provided. METHOD: Postal survey one year after policy instituted of Hutt district general practitioners. RESULTS: Sixty-three general practitioners replied (93% response). Eighty-one percent of general practitioners were in favour of the new policy or wanted it extended further, although 79% had noticed a slight increase in patient numbers. Most surgeries were less than 10 km from the hospital, 44% had one general practitioner, 38% had no practice nurse, 84% were staffed between 40-59 hours a week. No practice had staff on the premises between the night time hours of 8 pm and 8 am but all had after hours cover by telephone. Most practices were equipped to manage at least some emergency conditions: all had peak flow meters, 94% had nebulisers, 69% oxygen cylinders, and 47% had an ECG machine. Only two practices had slit lamps and plaster of paris facilities, and one a defibrillation machine. Almost all general practitioners suture wounds, strap ankles, and most treat fractures and pack noses. Seventy-five percent of general practitioners expressed a need for better communication with the Hutt Hospital emergency department. CONCLUSION: A general acceptance of the policy change by Hutt general practitioners although more research is needed to determine the impact of this change on patients. PMID- 1436843 TI - Management of unstable angina by the general practitioner, II. Issues in management. PMID- 1436844 TI - Anaesthesia in small hospitals. PMID- 1436846 TI - Mandatory reporting of child abuse. PMID- 1436845 TI - Laryngeal cancer in New Zealand. PMID- 1436847 TI - Screening for noninsulin dependent diabetes mellitus and impaired glucose tolerance in a Dunedin general practice--is it worth it? PMID- 1436848 TI - The Drug Tariff and crime. PMID- 1436849 TI - Diabetes-inpatient utilisation, costs and data validity, Dunedin 1985-9. PMID- 1436850 TI - Group Against Liquor Advertising (GALA) PMID- 1436851 TI - Sexual orientation versus sexual behaviour. PMID- 1436852 TI - Core health services. PMID- 1436853 TI - Meningococcal disease 1992. PMID- 1436854 TI - Pamidronate use in two cases of hypercalcaemia secondary to hyperparathyroidism. PMID- 1436855 TI - Ceftriaxone for paediatric bacterial meningitis: a report of 62 children and a review of the literature. AB - AIM: The purpose of this prospective study was to document the efficacy of ceftriaxone in the treatment of childhood bacterial meningitis in a general paediatric unit. METHODS: All children presenting with bacterial meningitis to Christchurch Hospital between January 1987 and June 1991 were enrolled in this prospective study and received ceftriaxone 100 mg/kg/d for seven days. Outcome was defined by parameters including mean time to fever defervescence, prolonged fever, days in hospital, seizures, and other acute neurological sequelae, requirement for ventilation, mortality and morbidity. Audiology was performed at six weeks and again at three months if abnormal. Neurodevelopmental assessment was performed at three months. Side effects were recorded. RESULTS: There were 62 evaluable children. The mortality rate was 4.8% (3 children). Two children (3.4%) had clinically detectable neurological sequelae at the three month assessment. The mean duration of stay was 8.7 nights. Five children (8%) required ventilation. Mild self limiting diarrhoea occurred in 29%. CONCLUSIONS: Ceftriaxone is an effective, safe and well tolerated antimicrobial for the treatment of childhood meningitis. It compares favourably with other equipotent antimicrobials. With a relatively long half life once daily administration is possible with a cost advantage. PMID- 1436856 TI - Sexually transmitted diseases amongst a sample of people seeking HIV testing. AB - AIMS: To examine the incidence of sexually transmitted diseases according to gender, age, sexual orientation, sexual behaviour and drug use. METHODS: Data were collected from 814 clients attending anonymously for HIV testing at the Burnett Centre in Auckland. During pretest counselling clients were asked questions designed to assess their risk of HIV infection including a detailed history of sexually transmitted diseases (STDs). RESULTS: Amongst attenders 44% reported at least one lifetime STD including 16% reporting more than one. Multiple STDs were not associated with gender or sexual orientation but they were associated with the practice of anal sex and with a history of multiple sex partners. Alcohol and drug use were also related to multiple STDs. For men the most common STD was NSU with 20% of them reporting it whereas for women genital warts was the most common reported by 18%. Amongst those under 20 years 9% reported genital warts, 7% NSU and 6% chlamydia. CONCLUSIONS: The findings confirm that it is sexual practices which put people at risk of infection from STDs rather than their sexual orientation. They also draw attention to the role that drugs and alcohol play in the practice of unsafe sex and the consequent transmission of STDs. Finally they suggest that screening for STDs as well as HIV in AIDS clinics should be encouraged. PMID- 1436857 TI - New inflammatory mediators and therapeutic agents: cytokines in rheumatoid arthritis. PMID- 1436858 TI - Child passenger fatalities and restraint use in Auckland. AB - AIMS: To determine the proportion of children killed as passengers in car crashes who were unrestrained and to estimate the reduction in mortality that might result from increasing child restraint utilisation. METHODS: All children killed as passengers in car crashes, over the period 1980-90, were identified from the Auckland coroners records. Data were recorded on sex, age, use and type of restraint, position within the motor vehicle, pattern of injuries and place of death. RESULTS: There were 49 children (25 male, 24 female) killed as passengers in car crashes over the study period (2.14/100,000/year). The median age was eight years (range 0-14 years). Of the 38 children for whom restraint use could be determined, 31 (81.6%) were unrestrained and seven (18.4%) were restrained. None of the children aged 0-2 years were restrained. Thirty-five children (71.4%) died at the scene of the crash, three (6.2%) died during transport to hospital, and 11 (22.4%) died in hospital. CONCLUSIONS: Based on overseas reports of the efficacy of child restraints, close to half (49%) of all child passenger deaths in Auckland could have been prevented with appropriate child restraint use. PMID- 1436859 TI - Elderly people referred for institutional care--is prior assessment necessary? AB - AIMS: To determine whether requests for placement of an elderly person into rest home or hospital care accurately predicted the final outcome and to identify factors influencing a move to institutional care. METHODS: Three month audit of all referrals to an assessment and rehabilitation unit for the elderly requesting rest home or hospital placement. Requests for medical advice or rehabilitation were excluded. RESULTS: Two hundred patients were studied (24.6% of all referrals). Placement was requested in a rest home in 132 and hospital in 68. Seventy-one (54%) patients referred for rest home placement were able to return to their own home and 64 remained there at six month follow-up. Hospital level care was assessed as appropriate in 62% of requests for this initially and at six month follow up. Age and diagnosis were not significant predictors of patients requiring placement. Overall, of 158 patients living at home referred for rest home or hospital care, 67 (42%) were managing at home six months later. CONCLUSION: Accurate assessment and treatment/management of elderly patients is necessary before recommending higher levels of care. Patients can be maintained in their current environment for longer than perceived by the referring doctor. This has important social and financial benefits. PMID- 1436860 TI - Do access factors affect utilisation of general practitioner services in south Auckland? AB - AIMS: To describe basic features of access to general practitioner services in south Auckland, and to examine the effect of different factors on utilisation of general practitioner services with particular attention to access issues. METHODS: A random population survey of relatively established residents was undertaken with the sample drawn from electoral rolls. A questionnaire was administered face-to-face by trained interviewers. RESULTS: Ninety-eight percent of respondents claimed to have a regular family doctor. The median travelling time to a respondent's general practitioner was 10 minutes. Ninety-five percent of respondents' general practitioners operated appointment systems. The median waiting time was 20 minutes, 30% felt the doctors fees stopped them going to the doctor sometimes. The average reported visiting rate was 6.9 visits per year. Poor perceived health, longer times with a given doctor and long waiting times were associated with decreased utilisation. Demographic factors were not associated with utilisation. Patient fees were not associated with utilisation in the sample. Only 23% of the variation in utilisation could be explained by the model. CONCLUSIONS: Long waiting times are associated with decreased utilisation in this population. Although there is significant dissatisfaction with general practitioner fees, this does not manifest itself in decreased utilisation. Only a small proportion of the variation in utilisation can be explained by linear models of the variables studied. PMID- 1436861 TI - Air cushion mower foot injuries. AB - AIMS: This study was undertaken to identify significant physical, social and psychological problems resulting from injuries caused to the feet by air cushion mowers. METHODS: Thirty-four patients seen with air cushion mower injuries were reviewed, either by personal assessment, or by questionnaire. RESULTS: A large number of patients had significant symptoms relating to their soft tissue or bone injuries, the majority experiencing some pain, and those who had amputations difficulty in some aspects of walking. CONCLUSIONS: Better education of the dangers of the misuse of these mowers may reduce the incidence of significant forefoot injuries. PMID- 1436863 TI - Health expenditure and the health reforms--a comment. PMID- 1436862 TI - Unknown immunodeficiency state: case report. PMID- 1436864 TI - Acute otitis media and facial palsy. PMID- 1436865 TI - Blood stored in operating theatres. PMID- 1436866 TI - Late haemothorax after oral vitamin K. PMID- 1436867 TI - Triazolam. PMID- 1436869 TI - Glutaraldehyde in general practice. PMID- 1436868 TI - Accountability and the health reforms. PMID- 1436870 TI - Reporting of child abuse and neglect. PMID- 1436872 TI - Increase in selenium status of Christchurch adults associated with deregulation of the wheat market. AB - AIMS: to determine whether there have been changes in the plasma selenium status of Christchurch adults between 1981 and 1992, and likely causes of any such changes. METHOD: selenium analyses were performed on plasma samples collected during the period. Changes in agricultural practices and importation policies were also examined. RESULTS: mean plasma selenium levels ranged between 46 and 54 micrograms/L (0.59-0.69 mumol/L) until 1987, after which there was a dramatic and sustained increase to between 66 and 70 micrograms/L (0.84-0.88 mumol/L) for 1988 91, with a 1992 mean of 80 micrograms/L (1.01 mumol/L). This increase closely follows the deregulation of the New Zealand wheat market and greater South Island consumption of wheat imported from Australia and the United States. Whereas flour was made from South Island wheat prior to 1988 and contained about 15 micrograms/kg selenium, flour manufactured by Christchurch mills in 1991 contained between 80 and 140 micrograms/kg. CONCLUSIONS: these results imply that as a result of current government policy, the population of Christchurch no longer has particularly low selenium levels. It follows that if there is an association between low selenium and any form of ill health, a declining incidence or severity in this population might be expected. PMID- 1436871 TI - Incidence of cancer among Pacific Island people in New Zealand. AB - AIM: to describe the epidemiology of new cancer registrations among Pacific Island people in New Zealand with a view to identifying important cancers for preventive activities. METHODS: new cancer cases registered with the New Zealand Cancer Registry of the Health Statistical Services for the decade 1979-88 were analysed. Cancer cases among Pacific Island people were compared with cancer cases among Maori and the remainder of the New Zealand population (other). RESULTS: while the number of cases reported among Pacific Island people was relatively small (1884), age standardised rates for cancer of all sites were much higher than age standardised rates for Maori and other populations. The age standardised rate (per 100,000 person years) for cancer of all sites among males in all age groups was 400 for Pacific Island, 308.8 for Maori and 295.3 for others. The age standardised rate for cancer of all sites among women in all age groups was 373.3 for Pacific Island women, 324.2 for Maori and 313.4 for other women. Liver cancer was more common among Pacific Island men than could be explained by temporary migration from the Pacific Islands for treatment. The age standardised rate for liver cancer was 28.2 for Pacific Island men, 11.4 for Maori and 1.9 for other men. Cancer of the cervix was the leading site among Pacific Island women as in Maori women, compared with breast cancer among women in the rest of the population. The age standardised rate for cervical cancer was 61.8 for Pacific Island, 69.0 for Maori and 59.3 for other women. CONCLUSION: in the decade 1979-88 there was an excess number of new registrations for some cancers described among Pacific Island people compared with Maori and other ethnic groups. Temporary migration from the Pacific Islands for treatment may explain some of the excess cases. PMID- 1436873 TI - Asthma in Maori people. PMID- 1436874 TI - Autologous blood transfusion in Auckland. AB - AIMS: To review autologous blood collection and transfusion practice in Auckland over the last five years. METHOD: Records of autologous blood collections were obtained from blood collection centre records and results of transfusions on patients from hospital notes. RESULTS: One hundred and sixty-four units of blood were collected from 77 patients. Seventy-five percent of the units collected were transfused. Most autologous blood was transfused to private hospital patients. Only 8% of patients required homologous blood. CONCLUSIONS: There has been a slow increase of autologous blood collection and transfusion in the Auckland area, as well as in the rest of New Zealand. The present risks of homologous transfusion, particularly since the introduction of hepatitis C testing, appear very low. A further expansion of the present autologous blood programme would entail increased expenditure and it is suggested that a critical cost benefit analysis would be useful before the programme is expanded. PMID- 1436875 TI - The bequest of human bodies for dissection: a case study in the Otago Medical School. AB - AIMS: To explore why and by whom body bequests to the Otago Medical School have been made since the 1960s. METHODS: We sent out a questionnaire to people who have bequeathed their bodies to the medical school, the people being randomly selected on the basis of the inclusion of the initial J in a forename. The questionnaire sought information on sex, marital status, age, occupation at the time of bequest and bequest information source, as well as reasons for the bequest, expectations of cadaver use and attitudes towards organ donation. RESULTS: The most common reasons for making a bequest were--to aid medical science, and gratitude to the medical profession. There was, however, widespread confusion between cadaver use for medical teaching and for research. CONCLUSIONS: These center around the ethical implications of our findings for organ donation and attitudes towards usage of the dead body. PMID- 1436876 TI - Severe Guillain-Barre syndrome during childhood responding to intravenous gammaglobulin. PMID- 1436877 TI - Initial warfarin treatment in hospital--room for less caution? A twelve month prospective audit. PMID- 1436878 TI - Sunscreens--a guide to their use. PMID- 1436879 TI - Dietary selenium. PMID- 1436880 TI - Dietary selenium. PMID- 1436881 TI - Health reforms. PMID- 1436882 TI - Streptokinase and low back pain. PMID- 1436883 TI - That blood pressure reading--a general practitioner who became a patient. PMID- 1436884 TI - Fats and melanoma. PMID- 1436885 TI - Isoprenaline infusion and right ventricular pacing in severe diltiazem poisoning. PMID- 1436886 TI - Medical residency in the USA. PMID- 1436887 TI - Planning is key to successful retirement. PMID- 1436888 TI - Council on Dental Care Programs forms committees to help resolve third-party problems. PMID- 1436889 TI - Financing oral health care. Can dentistry diversify the portfolio? AB - One of the easiest ways to measure socioeconomic status in 20th-century America is to look in the mouth. Socioeconomic status is directly related to access to oral health care. And access to oral health care is directly related to financing oral health care. PMID- 1436890 TI - Dental practices in New York State counties in the 1980s. AB - The number of dental practices, population per dental practice, dental employees and employee salaries in New York State counties changed during the 1980s. The following is a review of these developments. PMID- 1436891 TI - Galvanic corrosion of Class II amalgam restorations in contact with orthodontic brackets/bands. PMID- 1436892 TI - Fathers and sons. Practices not necessarily made in heaven. AB - Partnerships result in many pluses to a dental practice. Interpersonal relationships result in many minuses to the partners' rapport. This is magnified manyfold when the relationship is father and son. This article attempts to resolve some of the problems. PMID- 1436893 TI - Dental fellowships in developmental disabilities help broaden care of disabled. AB - Continuation of the national trend toward deinstitutionalization and community placement for persons with developmental disabilities, physical handicaps and other medical problems will mean increased demand for dentists trained to care for this segment of the population. The New York State Office of Mental Retardation and Developmental Disabilities now offers dental fellowships in developmental disabilities to help fill the learning gap. PMID- 1436894 TI - Clarification offered. PMID- 1436895 TI - The single compartment model applied to the large renal pelvis: a preliminary study. AB - Diuresis renography should exclude or confirm pelvi-ureteric junction obstruction. Numerous equivocal cases seen here had large renal pelves with slow emptying on frusemide diuresis. An attempt was made to relate the rate of emptying to the volume of the renal pelvis. The fully distended renal pelvis during frusemide diuresis appears to satisfy the criteria of the single compartmental model which predicts a linear relationship between volume and flow rate, i.e. F = [0.693 V0]/t1/2 where F is the flow rate, V0 is the volume and t1/2 the time at which half the tracer has disappeared. Clearance half-time was measured from the diuresis renogram curve. Volume was estimated from a longitudinal ultrasound image at the end of the procedure, using a volumetric version of Simpson's rule as a sequential slice technique, given a roughly circular transverse image. Of 18 kidneys in 14 adult patients, three had large volume pelves and short emptying times. The remaining 15 showed a roughly linear relationship between volume as estimated and clearance half-time. This appears to validate both the theory and the method and permits calculation of the pelvic outflow rate. An hypothesis to explain the large unobstructed renal pelvis is advanced. PMID- 1436896 TI - The effect of captopril on glucoheptonate uptake in experimental renal artery stenosis. AB - This study attempted to evaluate the role of glucoheptonate (GHA) in captopril renography in an in vivo laboratory investigation in which postcaptopril glucoheptonate uptake was analysed in awake 2KlC hypertensive rats. Clamped kidney uptake in a previous study was greater in the poststenotic kidney than in the normal kidney (P = 0.01) in rats with mild renal artery stenosis. A glucoheptonate renogram protocol was developed for use in rats anaesthetized with sodium pentobarbital. An 123I-hippuran scan was performed to determine the relative renal function, followed by a control 99Tcm-GHA scan. Five minutes after administering captopril, another 99Tcm-GHA scan was performed. Relative renal uptake was determined between 30 and 90 s postinjection. 99Tcm-GHA uptake in the clamped kidney was more than 50% of total uptake in 3/9 of the abnormal rats' control scans. No abnormal rats clamped kidney 99Tcm-GHA uptake was greater than 50% in the postcaptopril scans. Captopril reduced GHA uptake in all nine of the animals with baseline scans. These findings suggest that the laboratory observation of captopril induced paradoxically increased 99Tcm-GHA uptake in renal artery stenosis may not be observed scintirenographically. Moreover, the data support a potential value of glucoheptonate in captopril renography. PMID- 1436897 TI - Further characterization of iodide-induced hyperthyroidism based on the direct measurement of intrathyroidal iodine stores. AB - Clinical, scintigraphic and laboratory findings in a group of 23 hyperthyroid patients with inappropriate total intrathyroidal iodine pool (ITI), measured by X ray fluorescence, were compared to those of 25 hyperthyroid patients with low ITI. Differences are discussed which may be useful in the diagnosis of this clinical entity. PMID- 1436898 TI - A reconstitution protocol for Ceretec. PMID- 1436899 TI - Radionuclides and the investigation of peripheral vascular disease. PMID- 1436900 TI - Challenges for nuclear medicine in the 1990s. AB - This article discusses the problems facing nuclear medicine in the coming decade and outlines the areas in which new developments or expansion can be expected. The questions considered include legislative requirements, the need to educate the public and the medical profession on the strengths of nuclear medicine, approaches to cost-benefit analysis, and development of new technologies and new radiopharmaceuticals. There is also an evaluation of expansion in nuclear medicine using both existing methodology and new methodologies. PMID- 1436901 TI - The use of a new radiopharmaceutical, 97Ru-DISIDA, and of 99Tcm-sulphur colloid for the simultaneous evaluation of duodenogastric reflux and gastric emptying. AB - There is no consensus or a uniform technique for measuring gastric emptying and numerous modalities have been reported. We report here the results obtained using a modification of the published techniques for the simultaneous measurement of duodenogastric reflux and gastric emptying utilizing simultaneously the recently developed radiopharmaceutical 97Ru-DISIDA, intravenously, and the oral administration of 99Tcm-sulphur colloid incorporated in a 'solid' test meal. PMID- 1436902 TI - Venous thrombosis: a controlled study on the performance of scintigraphy with 99Tcm-HMPAO-labelled platelets versus venography. AB - Thirty-three patients with symptoms and signs of a deep venous thrombosis (DVT) were examined by contrast venography and radionuclide imaging with 99Tcm hexamethylpropyleneamineoxime (99Tcm-HMPAO)-labelled autologous platelets. There were 13 patients on heparin therapy and 20 without anticoagulation during the scintigraphy. Scintigraphy consisted of blood pool imaging at 5 to 20 min and accumulation imaging at 2, 4-6 and 18-24 h. In scintigraphy a positive finding was either a defect of radioactivity in the immediate blood pool phase or a hot spot indicative of accumulation of platelets in later phases. Fifteen out of 23 patients positive by venography were also positive by scintigraphy. Five of the eight false negative patients were on heparin treatment, two probably had DVT which were not quite fresh. The venography negative patients were also negative on scintigraphy. Nine out of 12 patients without anticoagulation had positive platelet accumulation compared with two out of 11 patients on heparin therapy. This difference was statistically significant (P less than 0.025). The sensitivity and specificity of platelet scintigraphy were 65 and 100%, respectively, in all patients and 83 and 100% in patients without anticoagulation. Our results suggest that scintigraphy with 99Tcm-HMPAO-labelled platelets is a useful alternative in diagnosing DVT in patients in whom a standard contrast X-ray venograph is contraindicated or otherwise unsuccessful. PMID- 1436903 TI - Diagnosis of venous thrombosis in the legs using 81Krm venography. AB - Contrast venography, the accepted gold standard for the diagnosis of venous thrombosis of the leg, is a painful and invasive procedure with late side effects. There is controversy in literature reports about the sensitivity of 99Tcm-macroaggregated albumin (MAA) phlebography: indeed, using 99Tcm-MAA, poor results are obtained when one has to detect calf vein thrombosis. As with other isotopic procedures requiring a pedal injection of the tracer, the use of an injectable solution of 81Krm is a nonspecific method, based upon the abnormality in flow in the deep venous system which results from a deep venous thrombosis. However, when compared with 99Tcm-MAA, 81Krm offers theoretical advantages for phlebographic studies of the lower limbs. In this work 24 patients were studied both with contrast phlebography and with 81Krm. Although 81Krm provided images of high quality, there was a lack of sensitivity below the knee, where false negative results were observed. This could be explained by the fact that the radionuclide venographic procedures usually visualize only one or, in some cases, two of the three deep veins of the calf. Moreover, accurate differentiation between superficial and deep veins in the calf often appears difficult, even using a tourniquet. PMID- 1436904 TI - Fate of isopropyl-iodoamphetamine (IMP) in rat liver microsomes. AB - Para-iodoamphetamines are currently used in nuclear medicine to detect brain perfusion abnormalities with tomoscintigraphy. Little is known about their metabolism pathways in rat and humans. N-isopropyl-125I-iodoamphetamine (IMP) interactions were studied with rat liver microsomes. The first dealkylated metabolite (IAMP) at low concentration gave a type I binding complex then, with a high concentration, a very stable type II complex with oxidized cytochrome P-450 FeIII. In contrast, IMP only gave a type I binding complex in the absence of NADPH. In the presence of NADPH, IAMP and IMP produced 455 nm absorbing complexes, which were enhanced when phenobarbital-treated rat liver microsomes were used. During in vitro metabolic activation, covalent binding of IMP and IAMP on rat liver microsomal proteins was observed. This process was mixed function oxidase (MFO) dependent. The covalent binding level was higher with IAMP and was not affected by flavine oxidase inhibitors. These results confirm the interaction of IMP and IAMP with microsome proteins and cytochrome P-450 and suggest that an N-oxidation of IMP occurs after N-dealkylation. As cytochrome P-450 and dealkylated IMP (IAMP) were found in brain, cerebral metabolism in brain and evolution of activity biodistribution with the course of time can be suggested. PMID- 1436905 TI - A review of the literature on nonsurgical treatment in tubal pregnancies. AB - In some cases tubal pregnancy resolves spontaneously. The risk of subsequent surgical intervention due to either tubal rupture or the entry criteria of the study varies from 0 per cent to 31 per cent. The major problem in nonsurgical treatment of tubal pregnancy is the absence of a parameter that reveals the threat of tubal rupture. In addition, data on the functional recovery of the fallopian tube are controversial. The scarcity of data on medical treatment with RU486, glucose 50 per cent, KCL, and actinomycin-D make proper evaluation impossible. Both MTX and prostaglandin treatment should be investigated further. Compiled data on prostaglandin treatment in cases of unruptured tubal pregnancy do not show better results than data on expectant management only. If, however, patients with initial serum hCG levels greater than 1000 mIU/ml or greater than 2500 mIU/ml are excluded from this therapy, the risk of tubal rupture diminishes. Side effects are minimal, especially if injection into the corpus luteum is omitted. Compiled data on MTX treatment in cases of unruptured tubal pregnancy show a crude risk of subsequent surgical intervention of 5 per cent. If patients with an initial serum hCG level exceeding 10,000 mIU/ml are excluded, the risk of tubal rupture is limited to 3 per cent. (The estimated risk of persistent trophoblastic activity after conservative surgical therapy is also 5 per cent.) Studies on the optimum MTX dosage, treatment scheme, and method of administration are still going on. Side effects are reversible and minimal. Theoretically, the local injection of MTX is more effective. Although often used to propagate a new way of treatment, fertility in the future is a questionable parameter in the evaluation of therapy. Fertility is influenced by so many factors other than the method of treatment that it can only be used for treatment evaluation in a case control or a randomized prospective study. Such a study has yet to be published. Besides the influence on future fertility, other results of treatment, such as morbidity, cost, and length of hospital stay should be taken into account. PMID- 1436906 TI - The new era in oral contraception: pills containing gestodene, norgestimate, and desogestrel. AB - The latest advance in the 30-year evolution of oral contraceptives (OCs) is the development of three new progestogens: desogestrel, norgestimate, and gestodene. These three new agents are derivatives of levonorgestrel, a gonane hormone, and have been used to develop pills that provide effective pregnancy prevention at lower doses than oral contraceptives using the older steroids. Desogestrel is a prohormone that must first be metabolized into its biologically active form. Norgestimate is already active, but it will be metabolized in part to levonorgestrel. Gestodene is biologically active in its native form. Among the improvements in metabolic parameters seen with this new generation of progestogens are a lack of impact on blood pressure, a balanced effect on coagulation, and a reduced impact on carbohydrate metabolism compared with earlier, higher-dose formulations. The new pills also seem to produce no negative effects on lipid and lipoprotein biosynthesis, and perhaps even improve the ratio of low-density lipoprotein to high-density lipoprotein. Cycle control with all three progestogens is improved, with much lower incidence of intermenstrual bleeding (IMB). Efficacy is as good as with other OCs. Another benefit of the new low-dose progestogens, however, is the low incidence of minor side effects observed in women using these contraceptives. Low incidences of weight gain, headache, and nausea were reported, and the dropout rate because of side effects was low in both international and US trials. Serious side effects are rarely seen with pills containing the new progestogens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1436907 TI - Cumulative Subject and Author Index. 1988-1992. PMID- 1436908 TI - Assessment of the fallopian tube. PMID- 1436909 TI - Review of the endometrial effects of estrogens and progestins. AB - Several controversial areas have been reviewed. It would seem from the evidence at hand that progression from endometrial hyperplasia to endometrial carcinoma does occur in a significant percentage of women and that endometrial hyperplasia, particularly adenomatous hyperplasia and atypical hyperplasia, must be regarded as premalignant changes. Gambrell believes that all stages of hyperplasia should be regarded as premalignant. Previous and retrospective studies provide evidence implicating estrogens in the causation of both endometrial hyperplasia and endometrial carcinoma. Although some of these studies may have design flaws, the amount of data is substantial. Prospective studies have demonstrated an increased risk of hyperplasia in women treated with estrogens. An increased risk of endometrial carcinoma in estrogen users compared with nonusers has been suggested even more recently. Reviewed as a whole, the cumulative evidence provided by these studies clearly supports this association, and it would appear the only issue left to resolve may be the magnitude of the association. Cyclic administration of estrogens may decrease the risk of development of endometrial carcinoma. It would seem, however, that such administration does not totally eliminate risk under any circumstances, and in fact, a dose-related relationship appears to persist. It seems well established that progestogens do decrease the risk of both endometrial hyperplasia and endometrial carcinoma associated with the administration of estrogen to peri- and postmenopausal women. Such reduction in risk is significant and lower relative risks in estrogen/progestogen treated women have been reported compared to untreated women. This reduction in risk has been reported in a variety of studies. Whitehead and co-workers have provided a clear biochemical mechanism for progestogen protection of the endometrium in the antagonism of estrogen at the endometrial cellular level. The evidence at hand in the literature would suggest that progestogens should be administered for at least 10 days per cycle. In summary, there is good evidence that the addition of a progestin to estrogen therapy prescribed for the symptoms of menopause provides protection from endometrial hyperplasia and related carcinoma. The protection conferred is greater than that afforded by cyclical estrogen-alone therapy, and allows for continuous therapy, hereby providing greater symptomatic relief. There is little evidence for adverse effects caused by the added progestins, but further studies of women on combined therapy will undoubtedly be warranted. PMID- 1436910 TI - Back to school with computers. PMID- 1436912 TI - Designing a computer-display shoot-out. PMID- 1436911 TI - Students and faculty benefit from interactive audio. PMID- 1436913 TI - Repurposing IVD to teach quality improvement. PMID- 1436914 TI - Labor and industry should cooperate to reduce the ergonomic injury rate. PMID- 1436915 TI - Health industry adjusts to specifics of bloodborne pathogens exposure rule. PMID- 1436916 TI - Body at work. PMID- 1436917 TI - Ergonomics: diagnosis and treatment for ailing workplace performance. PMID- 1436918 TI - Comprehensive eyewear programs maintain worker vision protection. PMID- 1436919 TI - Successful noise abatement program relies on engineering controls. PMID- 1436920 TI - Responders: levels and logic of respirators. PMID- 1436921 TI - Host defenses and bacterial resistance. AB - The amount of knowledge and understanding about the human immune system has expanded rapidly in the past several decades. The ability of the physician to care for pregnant women, specifically those with infectious diseases, can be enhanced through a basic understanding of host defenses and the normal alterations of these defenses encountered during pregnancy. A general understanding of bacterial resistance to antimicrobial agents will also aid the practitioner in selecting the appropriate setting and agent when prescribing these drugs. PMID- 1436922 TI - The penicillins. AB - The penicillins have played a major role in the treatment of many obstetric and gynecologic infections. The advent of the newer broad-spectrum penicillins has allowed their use as single-agent therapy for certain infections. Although toxicity is extremely low, disadvantages of their use include superinfection and induction of resistance. The cost of therapy is comparable with other antibiotics with similar coverage. PMID- 1436923 TI - Limited-spectrum (first-generation) cephalosporins. AB - Except in the treatment of pyelonephritis, the first-generation cephalosporins are rarely the first line drug of choice for any suspected infection in obstetrics. Other antibiotics have a narrower spectrum of antimicrobial coverage and are cheaper. Unless culture dictates the use of cephalosporins for main-line therapy, the use of first-generation cephalosporins should be limited to the treatment of pyelonephritis in pregnancy and for prophylaxis at the time of surgery. PMID- 1436924 TI - Extended-spectrum (second- and third-generation) cephalosporins. AB - The extended-spectrum cephalosporins provide better activity against gram negative bacilli and anaerobes than first-generation agents. Cefoxitin and cefotetan (second-generation) and ceftriaxone (third-generation) have excellent activity against B. fragilis and are useful in the treatment of postoperative infections and pelvic inflammatory disease. The extended-spectrum cephalosporins are as efficacious as first-generation agents for prophylaxis of cesarean section and hysterectomy. The first-generation drugs, such as cefazolin, are considerably less expensive than these newer compounds, however, making first-generation agents the drugs of choice when used for prophylaxis. The majority of the third generation agents should be reserved for the treatment of meningitis and resistant nosocomial infections. PMID- 1436925 TI - Imipenem-cilastatin. AB - Imipenem-cilastatin, with its broad spectrum of activity and relative safety, offers an excellent alternative for the treatment of many obstetric and gynecologic infections. In addition, the possibilities for intramuscular administration give clinicians additional treatment options. Because of the relatively high cost of imipenem-cilastatin, it should not be considered "first line" therapy for most obstetric and gynecologic infections at present. Misuse and overuse of imipenem-cilastatin will result in the further development of resistant organisms, as has already been seen with many other antibiotics, and continued monitoring of susceptibility patterns is necessary. PMID- 1436926 TI - Clindamycin. AB - Clindamycin has been extensively used in the therapy of obstetric and gynecologic infections for over 20 years. This antibiotic is well known for it activity against anaerobic bacteria, particularly beta-lactamase-producing strains of the Bacteroides species. Clinicians should also recognize its very good activity against aerobic gram-positive cocci, such as the group B streptococci, but be aware of its absence of activity against aerobic gram-negative rods, such as E. coli. In combination with an aminoglycoside, clindamycin has become the standard by which other antimicrobials have been judged in the treatment of pelvic infections. A dose of 900 mg administered intravenously every 8 hours is recommended when treating the serious infections discussed. Although concern about the potential side effect of pseudomembranous colitis is valid, in practice, this is an uncommon problem that responds well to the discontinuation of clindamycin and to the treatment of the C. difficile-induced condition with vancomycin or metronidazole. PMID- 1436927 TI - Metronidazole. AB - Metronidazole has proven to be a useful and inexpensive antibiotic for the treatment of T. vaginalis and bacterial vaginosis. Few alternatives exist for these two specific indications, and metronidazole will continue to play a primary role in therapy. Oral metronidazole continues to be a very inexpensive alternative to oral vancomycin for the treatment of C. difficile-induced pseudomembranous colitis. For the treatment of moderate to severe mixed aerobic/anaerobic pelvic infections, metronidazole should be considered secondarily in patients who have failed other multiple- or single-drug regimens or in patients who are infected. with anaerobic organisms resistant to other commonly used agents including clindamycin, cefoxitin, cefotetan, or ampicillin/sulbactam. Metronidazole is not a first line drug of choice for antibiotic prophylaxis in obstetric and gynecologic patients. PMID- 1436928 TI - The aminoglycosides. AB - The three most commonly used aminoglycosides in obstetrics and gynecology are gentamicin, tobramycin, and amikacin. These drugs bind to subunits of the ribosome and inhibit bacterial protein synthesis. They are primarily active against aerobic gram-negative bacilli. Their principal adverse effects are nephrotoxicity, ototoxicity, and neuromuscular blockage. They may be administered intramuscularly or intravenously and usually are used in combination with other drugs for treatment of disorders such as pyelonephritis, chorioamnionitis, puerperal endometritis, and pelvic inflammatory disease. PMID- 1436929 TI - Aztreonam. AB - Aztreonam is a synthetic monobactam antibiotic that has excellent activity against aerobic gram-negative bacilli. It can be used as a single agent for the treatment of upper urinary tract infections caused by organisms resistant to the cephalosporins and ampicillin. It also can be administered in combination with a drug such as clindamycin for treatment of pelvic inflammatory disease or postoperative pelvic infections. PMID- 1436930 TI - The quinolone antibiotics. AB - The fluorinated quinolones are synthetic derivatives of nalidixic acid. They are well absorbed when administered orally and have an extended duration of action. They are of primary value in treating gonorrhea and complicated urinary tract infections in nonpregnant women. PMID- 1436931 TI - Erythromycin. AB - Even with the continuing emergence of new antibiotics, erythromycin continues to be used extensively in obstetrics and gynecology. It is inexpensive, with a long history of usage and proven safety. When oral erythromycin preparations are given in the correct dose and with proper timing in relation to meals, no individual preparation offers a significant therapeutic advantage. Its uses include the treatment of respiratory tract infections, chlamydial and other genital tract infections in pregnancy, puerperal mastitis, and acute conjunctivitis of the newborn. PMID- 1436932 TI - The tetracyclines. AB - The tetracyclines are inexpensive drugs that are of primary value in treating nonpregnant women who have acute urethral syndrome or endocervicitis due to Chlamydia trachomatis. They are contraindicated in pregnancy because they are injurious to fetal teeth and bone. PMID- 1436934 TI - Topical antifungal agents. AB - Current knowledge of fungal cell architecture and biochemistry allows limited understanding of the mode of action of presently available topical antifungal agents. Nystatin, first introduced in the 1950s for treatment of vulvovaginal candidiasis, has been surpassed by the imidazoles and triazoles as the first choice of treatment for vulvovaginal candidiasis. The lack of clear superiority of any one azole agent or dosing regimen leads some authors to recommend a short course of therapy (1-3 days) for acute uncomplicated candidal vaginitis using factors including anatomic distribution of inflammation and patient preference (such as previous hypersensitivity or allergic reaction to the agent, the cost of the agent, and the preferred vehicle for administration of the agent) to choose the specific antifungal agent (see Table 1). Recurrent cases or treatment during pregnancy may require longer therapy (6-14 days), again using an agent chosen because of these factors. Although theoretic risks may exist, actual harm to the fetus or pregnancy has not been demonstrated with the use of the topical azoles during any trimester of pregnancy. The development of antimycotic resistance need not be considered in infrequent and occasional episodes of candidal vaginitis, and it is rarely a cause of treatment failure even in chronic or recurrent cases. PMID- 1436933 TI - Antiviral agents. AB - Antiviral agents are less numerous and often more toxic than antibacterial agents. Acyclovir is commonly used for suppression and treatment of recurrent genital herpes simplex virus and may be indicated for pregnant women with disseminated herpes. Zidovudine is indicated for pregnant women with human immunodeficiency virus infection who have low CD4 lymphocyte counts. Ganciclovir, vidarabine, ribavirin, amantadine, didanosine, and foscarnet are rarely indicated in gynecology and are not recommended for use in pregnancy. PMID- 1436935 TI - Evaluation and management of orofacial sensory nerve injuries. AB - Sensory disturbances can occur as a result of a number of dental procedures, maxillofacial injuries and pathology. The dentist is expected to inform patients of the likelihood of nerve injury prior to conducting invasive procedures. If a patient develops a sensory deficit after treatment, the practitioner should be aware of objective means of assessment of the deficit and techniques available for management. Our understanding of nerve injury, regeneration and treatment has markedly progressed in recent years. This paper provides current information on the prevention and management of neurosensory disturbances likely to be encountered in dental practice. PMID- 1436936 TI - Case Western Reserve University School of Dentistry: a brief history. PMID- 1436937 TI - Asian Americans: an increasing reality in the population and the dental profession. AB - Asian Americans are one of the fastest growing minorities in the United States. The use of services by this diverse population can and is affected by a host of demographic, cultural and language factors. But little to no data on the oral conditions of this minority group are available. PMID- 1436938 TI - Temporal arteritis mimics TMJ/myofascial pain syndrome. AB - Dental pathology is definitely the most common cause of orofacial pain. Dentists astutely diagnose and treat the various pathologic dental conditions. The restoration of the masticatory system is usually achieved in a proficient, straightforward and predictable manner. Certain patients' orofacial pains do not have a dental etiology and are refractory to treatment. The protean manifestations of temporal arteritis may present with major pain complaints mimicking dental pathology. A case report of such a patient is presented. PMID- 1436939 TI - A reddish-blue gingival nodule. PMID- 1436940 TI - Low grade pain and mandibular expansion associated with a radiopaque lesion. PMID- 1436941 TI - Communicating costs and methods of infection control to your patients. PMID- 1436942 TI - Current trends in periodontal regeneration: a review and case report. PMID- 1436943 TI - Should we or shouldn't we treat condensing osteitis with root canal therapy? AB - The intent of this article is to review with the dental clinician the literature concerning a lesion labeled condensing osteitis. A radiographic and histologic picture is presented along with etiology and diagnosis. A conclusion is drawn from the available literature to treat these lesions with endodontic therapy. PMID- 1436944 TI - Is there a shortage of dental hygienists? AB - Dental hygiene faculty from the Ohio State University, working under a grant from the Ohio Dental Association, surveyed licensed dentists and dental hygienists in Ohio in order to determine work-related concerns and possible solutions to perceived shortages of hygienists. There were 585 respondents from those selected through stratified systematic sampling based on state dental district for a 69% rate of dentist return and a 73% rate of hygienist return. The joint surveys assessed attitudes and documented experiences in several categories: practice background, opinion about hygiene employment shortage, compensation, aspects of hygiene satisfaction, reasons for ever terminating hygiene practice and future conditions persuading a return to hygiene practice. This article, the first in a series, presents findings from the survey of dentists relative to a perceived shortage of clinical dental hygienists. Forty-eight percent of dentist respondents believe that there is a shortage, while 52% are either not sure or believe there is no shortage. Those sensing a shortage have either tried to find a hygienist and could not believe there is a smaller pool to choose from, or have heard that colleagues have been unable to find a hygienist. Solutions to the shortage focus on better recruitment of qualified students, encouraging reentry of non-practicing hygienists, and promoting retention of hygienists in existing practices. Less frequently, dentists suggest starting new hygiene programs or training hygienists by preceptorship. PMID- 1436945 TI - Results of the Ohio non-patient Dental Board examination for 1990-91. PMID- 1436946 TI - Comparison of infection control procedures in states with and without infection control rules. PMID- 1436947 TI - Skeletal variations of the seventh cervical vertebrae in the mouse with special reference to the foramina transversaria and the accessory foramina. AB - The formation of foramina transversaria in the seventh cervical vertebra of CBA and C57BL mice and their offspring is found to behave as if it is determined by a single semi-dominant gene. The accessory foramina of Weber (1950) are investigated in the same material. These foramina are classified into two types and their heredity is evaluated. PMID- 1436948 TI - A transmission electron microscopic study of macromelanosomes in sporadic dysplastic naevi. AB - Melanosomes in sporadic dysplastic nevi were examined by transmission electron microscope. In particular the structure of macromelansomes was observed. Macromelanosomes were present in both nevus cells and keratinocytes. They were round and consisted of a core structure and a cortex structure. The core was composed of electron-dense amorphous material and electron-lucent microvesicles. The cortex contained grains of different sizes and electron densities. Occasionally small melanosomes were observed in the cortex. Electron-lucent microvesicles were also present in small spherical and ellipsoid melanosomes. Melanosome complexes observed in nevus cells contained degrading melanosomes with electronlucent microvesicles, dispersed microvesicles and grains. Melanosome complexes with structures resembling those found in macromelanosomes were also present. The result of the investigation suggests that melanosome complexes found in nevus cells might become macromelanosomes through autophagy. PMID- 1436950 TI - Stereo architecture of the lamina propria in the mouse laryngopharynx in scanning electron microscopy. AB - In the ventral wall of the mouse laryngopharynx, a fairly large number of the epithelial papillae containing taste bud (provisionally denominated the pharyngeal papillae) were observed. The NaOH cellmaceration method was applied in order to demonstrate the stereo architecture of the connective tissue papillae (CTP) of the pharyngeal papillae. The CTP appeared as a cylindrical wall surrounding a round depression, and consisted of a delicate meshwork of collagen fibrils. It is suggested that the CTP constitute the skeletal framework of the pharyngeal papillae and that the round depression corresponds to the site of taste bud. Furthermore, the collagen fibrillar architecture in the extrapapillary region appeared to be arranged to meet specific functional needs. That is, in the rostral end of the laryngopharynx, the collagen fibrils ran solitarily to form a coarse meshwork and seemed to allow the epithelium a certain degree of freedom of motion in swallowing. On the other hand, in the caudal part the fibrils concentrated into the thick bundles of the fibers running side by side along the long axis of the laryngopharynx and, therefore, appeared to play an important role in resisting the excessive stretching force. PMID- 1436949 TI - Fine structure of developed human tongue muscle. AB - The purpose of this study was to clarify the relationship myofibrils, mitochondoria and other cytoplasmic organella in the developed lingual muscle (vertical, transverse, and longitudinal) by using various microscopic levels: light, scanning electron, and transmission electron. The tongue muscles were examined in seventeen autopsy specimens: eight, 12-32 weeks gestation and ten adults (five male, five female; 54-93 years). The muscle fiber rapidly developed. A large number of mitochondoria and glycogen granules increased and the size of myofibrils in the middle stage also increased, ranging from 24 to 28 weeks gestations. The developed myofibrils were differentiated, the VL and TL at first are developed before the LL developed. These results suggest that the lingual intrinsic muscle have differences in properties during development. PMID- 1436951 TI - Scanning electron microscopic study on the lingual papillae in the Manchurian chipmunk, Tamias sibiricus asiaticus. AB - The superfacial structures of the tongues in the Manchurian Chipmunk, Tamias sibiricus asiaticus, were observed by scanning electron microscope. The tongues were long, tapering, narrow and thick with a long apical free portion and a small lingual prominence in the posterior half. In this animal, three circumvallate papillae were present in an inverted triangle, a minority of conical papillae on the pharyngeal part and parallel large conical papillae on the lateral border. The fungiform papillae were scanty on the dorsal surface. These characters suggested this animal was more primitive than the others in rodents. PMID- 1436952 TI - Insertions of the lumbrical and interosseous muscles in the human foot. AB - The lumbrical and interosseous muscles in twenty-five feet of Japanese adult cadavers were dissected. The lumbrical muscles mainly continued into the dorsal aponeuroses or the terminal tendons of the extensor digitorum longus muscle, though they occasionally issued some accessory and slender tendons inserting into the bases of the proximal phalanges. Rarely, the lumbrical muscle showed an atavistic anomaly. In this anomaly, the lumbrical muscle was divided into two tails which continued into the bases of the proximal phalanges of the contiguous toes. The plantar and dorsal interosseous muscles were mainly attached to the bases of the proximal phalanges. Frequently, the plantar and dorsal interosseous muscles issued some accessory and small tendons continuing into the dorsal aponeuroses. This fact suggests that the plantar and dorsal interosseous muscles in the foot, like the palmar and dorsal interosseous muscles in the hand, are composite muscles derived from the flexor brevis, contrahens and other muscles. PMID- 1436953 TI - Anatomical study of the accessory mental foramen and the distribution of its nerve. AB - We examined the range of the accessory mental foramen [AMF] and its accessory mental nerve in three Japanese cadavers. The diameters of the AMF were relatively small: 0.74 mm, 0.80 mm and 0.89 mm. The distances between the mental foramen and AMF were: 0.67 mm, 2.1 mm and 5.74 mm. The distribution of the accessory mental nerve was different in the three cases. These nerves communicated with the branches of the facial and buccal nerves. PMID- 1436954 TI - A supernumerary muscle between the adductors brevis and minimus in humans. AB - In order to elucidate the nerve supply of a supernumerary muscle observed between the adductors brevis and minimus in humans and to investigate its true nature and mechanism of formation, 100 body halves from 50 adult Japanese cadavers were subjected to gross anatomical examination. A supernumerary muscle was noted in 33 (33.0%) out of the 100 thighs. In each of these thighs, it arose from the upper part of the inferior ramus of the pubis and ran obliquely downwards and laterally. It was inserted into the anterior surface of the insertion aponeurosis of the adductor minimus (17/33 thighs, 51.5%), the upper part of the pectineal line (9/33 thighs, 27.3%), or the posterior side of the base of the lesser trochanter (7/33 thighs, 21.2%). It was supplied, from its posterior aspect, by a filament from the twig originating from the posterior branch of the obturator nerve and being distributed to the superficial fasciculus of the obturator externus (18/33 thighs, 54.5%) or by a twig directly originating from the posterior branch (15/33 thighs, 45.5%). The obturator nerve received fibers from L1234 (4/33 thighs), L234 (25/33 thighs), L2345 (2/33 thighs) or L34 (2/33 thighs) and, moreover, its posterior branch ran through (25/33 thighs, 75.8%) or over (8/33 thighs, 24.3%) the obturator externus to emerge into the thigh. Based on the topographical-anatomical relationships of this muscle to its nerve supply, it seems probable that it is formed by separation from the superficial layer of the obturator externus and changes into an independent structure during the process of ontogeny. Furthermore, from a statistical standpoint, the segmental composition or course of the obturator nerve is not related to either the formation or incidence of this muscle. PMID- 1436955 TI - Morphological study of parafollicular cells and the parathyroid gland in the house shrew (Suncus murinus). AB - A morphological study of parafollicular cells in the thyroid gland and parathyroid gland of the house shrew (Suncus murinus) was made. The results indicated that (1) there were two pairs of parathyroid glands which were located in the upper part of the house shrew thyroid gland, (2) the volumes of the house shrew parathyroid glands ranged from 0.014 to 0.079 mm3, (3) the number of parafollicular cells along the follicles was largest in the upper part of the thyroid lobe, while no parafollicular cells were present in the isthmus, and (4) there were about 20 parafollicular cells per 100 follicular cells and 1.519 parafollicular cells per follicle. The number of parafollicular cells per 100 follicular cells was thus about 5 times larger than that in rats and the number of parafollicular cells per follicle about 2.5 times larger than that in rats. PMID- 1436956 TI - Development of collagen fibers and vasculature of the fetal TMJ. AB - Using 12 human fetuses, histological development and changes in connective fiber structure and fine vascular patterns have been investigated in various fetal gestational stages by light and scanning electron microscopy. The main arterial supply of the articular disc was from the bilaminar region and pterygoideus lateralis muscle. The vascular network on the disc surface was related with fluid secretion. When the bilaminar region was compressed, it caused ischemia and fibrosis as the main pathological changes in TMJ derangement. A decrease in fluid from blood vessels might occur in TMJ degeneration. Collagen fibers in the disc passed mainly anteroposteriorly. In the anterior and posterior bands, muscular tendon fibers came from the pterygoideus lateralis muscle and superior stratum of the bilaminar region. In the posterior band three-dimensional structures of collagen fibers suitable for load bearing were observed. The compass network and process on the disc showed the normal structure that is formed gradually and has functions including dispersion, pressure bearing, friction-proofing and storage of the synovial fluid. Attachments of the disc were suitable for disc function. Large elastic fibers in the posterolateral part of the superior stratum of the bilaminar region may be antagonistic to the upper head of the pterygoideus lateralis muscle fibers passing medioanteriorly, indicating that this antagonism is available for disc function. PMID- 1436957 TI - Arterial supply of the masseter muscle in the lion (Panthera leo). AB - There are few reports on the vascular system of the lion or Panthera leo except for that on the facial artery investigated by Lin and Takemura (1990). Morphological analysis of the masseter muscle of the lion according to the muscle tendon theory has been performed only by Takemura et al. (1991). The present authors attempted to elucidate the blood supply of the masseter, using 3 lion heads injected with acryl plastic into the carotid system by the plastic vascular injection method. This description is based on examination of the detailed laminar formation of the masseter. The findings are discussed in comparison with those of the felid family in carnivorae. Masseteric branches of the superficial temporal, buccal and facial arteries were distributed to the primary sublayer of the superficial layer, those of the above arteries and the masseteric artery to its secondary sublayer, the intermediate layer and the anterior and posterior portions of the deep layer, and those of the superficial temporal and masseteric arteries to the primary sublayer of the posterior portion of the deep layer. The maxillomandibularis muscle was supplied by the buccal and masseteric arteries and the zygomaticomandibularis by the superficial temporal and posterior auricular arteries as well. No gross differences between the lion and cat were observed in arterial supply of the masseter proper and improper, although the superficial temporal artery was distributed only to the superficial and intermediate layers in the cat but to all the deep layers in the lion. PMID- 1436958 TI - Case of an abductor pollicis longus muscle: variation or differentiation? AB - A variation of the abductor pollicis longus muscle in a 65 year old cadaver was encountered during routine dissection in our department. The muscle was found to split into two bellies and give off two tendons, one of which inserted to the abductor pollicis brevis, opponens pollicis and flexor pollicis brevis muscles. The other tendon inserted to the first metacarpal bone which is considered a normal insertion site for the abductor pollicis longus muscle. PMID- 1436959 TI - A variation of a coeliac trunk. AB - The coeliac trunk is a wide branch of the abdominal aorta which arises from just below the aortic hiatus. It is about 1.25 cm. long (5). In our cadaver the length of the coeliac trunk was observed to be 4.5 cm. Additionally the inferior phrenic arteries which normally arise from the abdominal aorta were derived from the coeliac artery. PMID- 1436960 TI - Age estimation from second metacarpals in children. AB - On the basis of cross-sectional data of 630 boys and 611 girls aged 0 to 19 years investigated during 1959-60, the present study attempts to estimate age from skeletal maturity and measurements (length, width and cortical thickness) of an isolated second metacarpal. A combination of the maturity score with the bone length gives a better estimate of age than either one of the bone measurements or a combination of them. However, the maturity score alone does not necessarily provide a better estimate of age than the bone length. In skeletal remains of immature children, the epiphysis is not usually available to estimate age. Age could be estimated by means of multiple linear equations from the diaphyseal length and width of the second metacarpal with a standard error of 1.26 years in immature children aged 6 to 17 years, regardless of sex. Although, this method certainly seems to be useful for age estimation of a population, it is not necessarily applicable to individuals. In addition, the equation obtained from the variables in this series is not universally applicable to other populations or to Japanese of earlier eras, with the same degree of certainty. PMID- 1436961 TI - Microvascular architecture of the lingual papillae in the Japanese monkey (Macaca fuscata fuscata). AB - The microvascular architecture of all kinds of lingual papillae in the Japanese monkey was investigated on plastic corrosion casts and epithelium-separated specimens under a scanning electron microscope. Three kinds of the filiform papillae were observed; the circularly-arranged papillae with a small papilla in the center on the lingual apex, a simple large conical papilla with a bilateral pair of spines on the lingual body and the aggregated filiform papillae on the top of an epithelial projection on the lingual radix. Five to eight capillary loops were arranged in a circle of the above filiform papillae on the lingual apex. Arterioles ascended in the filiform center on the lingual body to form an intrapapillary network in the shape of a large cone, from which capillary loops were observed only on the top surface of the papilla. Capillary loops arising from the subepithelial capillary network in the epithelial projection were distributed to each filiform papilla on the lingual radix. Globular fungiform papilla on the lingual apex were supplied by capillary loops radiating from the intrapapillary capillary network. Cylindrical fungiform papillae on the lingual body were supplied by capillary loops only on the top surface of each fungiform papilla without any loop formation on the lateral surface. Four vallate papillae, a medial and lateral pair, were supplied by arterioles ascending in the papillary center to form an intrapapillary capillary network, from which capillary loops were sent off on the top surface of the papilla and formed a network in the lateral surface. Each foliate papilla was supplied by an arteriole passing through each papillary center along the long axis and 5 or 6 capillary loops from the arteriole on the frontal section. Every lingual papilla was supplied by a characteristic microvascular pattern, which correlated closely with the location of the papillae and areas reflecting the regional role of the tongue movement, especially in the filiform and fungiform papillae. PMID- 1436962 TI - Informed choice, not informed consent. PMID- 1436963 TI - Outcome of treatment for bilateral congenital cataracts. AB - The outcome of treatment for bilateral congenital cataracts was studied retrospectively in a group of 51 patients. Two major categories of lens opacities were identified. In the first category, the opacities were extensive and visual impairment was evident early in the first year. These cataracts often occurred in eyes with small corneal diameters and poorly dilating pupils. Postoperative strabismus was nearly universal; nystagmus developed in over 50%; and late onset open-angle glaucoma developed in 8 of the 29 patients studied. Early surgery did not seem to abort the development of nystagmus in this group of patients. In the second category, the lens opacities were partial, often lamellar in configuration, and visual impairment was less severe. Surgery was usually performed after 3 years of age, with good visual results if the opacities were symmetrical and there was no nystagmus. No deprivation amblyopia developed in this group, even when surgery was delayed into the second decade. Strabismus developed postoperatively in about a third, but so far, no delayed open-angle glaucoma has been identified. PMID- 1436964 TI - Peribulbar anesthesia for primary vitreoretinal surgery. AB - We prospectively studied the efficacy of peribulbar anesthesia in 76 consecutive patients who underwent vitreoretinal surgery. The mean duration of anesthesia was 124.74 +/- 50.17 minutes, and the mean duration of akinesia, 151.5 +/- 54.45 minutes. Adequate anesthesia and akinesia, independent of the duration of surgery, was obtained in 26 of 33 (78.8%) patients who underwent vitrectomy; 9 of 32 (28.1%) who underwent scleral buckling; and 2 of 11 (18.2%) who underwent vitrectomy combined with scleral buckling. In all, topical and systemic supplementation of drugs for inadequate anesthesia or akinesia allowed 32 of the 33 (97%) vitrectomies, 30 of the 32 (94%) scleral buckling procedures, and all 11 of the combined surgeries to be completed as planned. Three (4%) patients vomited, moved, or were restless, resulting in an operative complication or postponement of surgery. Fifty-eight (76%) said they would desire similar anesthesia if subsequent surgery was needed in the same or fellow eye. We conclude that peribulbar anesthesia should be considered primarily for patients requiring vitreous surgery alone, and as an alternative for patients requiring scleral buckling or combined surgery for whom general anesthesia is contraindicated. PMID- 1436965 TI - Intraoperative application of 5-fluorouracil during trabeculectomy. AB - We report the preliminary results of the first 20 consecutive cases in which the antimetabolite 5-fluorouracil (5-FU) was applied directly beneath the conjunctival flap during trabeculectomy in high-risk patients. Seventeen were considered early successes, with 3-month postoperative intraocular pressures less than 21 mmHg, representing at least a 20% decrease from preoperative values. Successful blebs were pale, with conjunctival microcysts and without significant vascularization over the trabeculectomy site, similar to the appearance of blebs in eyes administered postoperative subconjunctival injections of 5-FU. There were no cases of corneal epithelial defects, and no eyes had lost more than one line of preoperative vision at the time of last follow up. Although the longer term efficacy of this method is unknown, these results suggest that it may represent a safe and effective alternative for administering 5-FU. PMID- 1436966 TI - Measurement of progressive disc change in glaucoma. AB - We describe a videographic procedure for detecting minute changes in disc topography of glaucomatous eyes that involves measuring the displacement of selected circumlinear vessels. The problem of recognizing the difference between parallactic errors and true changes in topography is emphasized. PMID- 1436967 TI - The early cell kinetic response during healing of corneal epithelial wounds. AB - The labeling index and the mitotic rate were measured at 4-hour intervals during the first 24 hours after a central abrasion had been made in the corneal epithelium of six groups of four rats each. The proliferative response was noted in the conjunctival, the limbal, and the corneal epithelium. After 24 hours, the density of epithelial cells was equal throughout the corneal epithelium, but there was only half the normal number of cells. Physiological mechanisms seem strongly to regulate the total number of cells per square unit throughout the healing corneal epithelium, but the nature of these mechanisms is unknown. PMID- 1436968 TI - Posterior relaxing retinotomies: analysis of anatomic and visual results. AB - Fifteen eyes with complicated retinal detachments--11 with proliferative vitreoretinopathy (C3 D3), 2 with posterior segment trauma, and 2 with inflammatory retinopathy--were treated with vitrectomy, membrane peeling, and large posterior retinotomy. All posterior relaxing retinotomies were circumferential, including temporal quadrants in all cases. With a minimum follow up of 6 months, 12 eyes (80%) were attached posterior to the retinotomy. Reproliferation resulted in redetachment in 3 eyes (20%). Visual acuity improved in 53%, remained unchanged in 20%, and decreased in 27%. Of the 11 eyes that achieved stable or improved visual acuity, 5 (45%) achieved 20/400 to 20/25 vision, 5 achieved counts fingers perception, and 1 patient remained stable at hand motion perception. Of all the eyes undergoing surgery, hypotony (intraocular pressure < 5 mm Hg) occurred in 6 eyes (40%); 3 of these were among the 12 eyes with attached retinas. PMID- 1436969 TI - The use of fibrin glue in mucous membrane grafting of the fornix. AB - We report using a fibrin-glue tissue adhesive in place of sutures to place a full thickness mucosal graft into a defect created in a scarred fornix of an ophthalmic socket. This technique minimizes tissue trauma and aids hemostasis and healing. PMID- 1436970 TI - Beheading the pterygium. AB - I describe a safe, easily learned, accessible, and inexpensive method for excision of the pterygium head using the tip of a 23-gauge needle as a cutting tool. The incision is controlled precisely, and excision of unaffected tissue, particularly at the limbus, is minimized by using point cutting edge techniques and by varying tissue tension to control tissue sectility ("cuttability"). PMID- 1436971 TI - Comparison between B-scan ultrasound and MRI in the detection of diabetic vitreous hemorrhage. AB - The efficacy of proton magnetic resonance imaging (MRI) was evaluated and compared with that of B-scan ultrasound in the detection and differentiation of diabetic vitreous hemorrhage. Although conventional spin-echo MRI could not locate vitreous hemorrhages, gradient-recalled-echo (GRE) MRI readily did so. The aberrant signals appeared to originate from the interfacing between hemorrhages and the vitreous, and possibly also from the paramagnetic effect of the ferrous ion. The information provided by boundary/susceptibility detection, unique to the GRE sequence, is useful in delineating the extent of vitreous hemorrhage and hemolysis. However, for the diagnosis and follow up of diabetic vitreous hemorrhages, MRI appears no more informative than B-scan ultrasonography. PMID- 1436972 TI - Combined cataract-glaucoma surgery using the THC:YAG (holmium) laser ab interno without gonioscopy. AB - We describe a simple method of combined cataract-glaucoma surgery, involving use of the THC:YAG (holmium) laser ab interno, without gonioscopy, in which the initial cataract incision remains small and the glaucoma filtering procedure can be completed relatively quickly, with minimal surgical manipulation of the conjunctiva. In a series of 15 eyes (13 patients) with visually significant cataracts and medically uncontrolled glaucoma, followed for an average of 14 weeks (range, 1 to 26 weeks), 13 of the 15 eyes had decreased IOP. Visual acuity was improved in 9 eyes, remained the same in 4 eyes (with age-related macular degeneration), and was worse in 2 eyes (with opacification of the posterior capsule sufficient to account for the decrease in acuity). PMID- 1436973 TI - Small-incision manual extracapsular cataract extraction using selective hydrodissection. AB - Hydrodissection is a technique in which balanced salt solution is injected through a cannula into various layers of a cataractous lens to separate the lens lamella in a nonspecific location. Selective hydrodissection allows separation of the lens lamella at different desired anatomical layers. The technique allows the smallest possible nucleus, ie, the hard-core nucleus, to be hydroexpressed as a separate entity, requiring, correspondingly, a relatively small capsulorhexis and limbal incision. Then, in a second maneuver, the epinucleus, which engulfs the hardcore nucleus to form the adult nucleus, also can be aspirated or hydroexpressed as a whole. Selective hydrodissection permits scleral incision and stitchless surgery in planned extracapsular cataract extraction and also may serve as an intermediate step for surgeons who wish to convert to or learn phacoemulsification techniques. PMID- 1436974 TI - Filtering seton implant for glaucoma: initial animal trial. AB - A newly developed silicone filtering seton device was implanted in each of five eyes of four rhesus monkeys after they had undergone extensive argon-laser trabeculoplasty to raise their intraocular pressure (IOP). One animal (one implant eye) was killed at 6 weeks. The other three animals (four implant eyes) were observed for 17 to 24 months following implantation surgery. Mild to moderate postoperative inflammation subsided during the first postoperative week. The eyes remained quiet throughout the remainder of follow up. The postoperative IOPs varied between 18% and 70% of the IOPs at the time of implant surgery. In the three monkeys that had unilateral surgery, the IOP at the final follow-up measurement was equal to or lower than the IOP in the unoperated fellow eye. In the monkey that had bilateral surgery, both of the final IOPs were lower than the preoperative ones. PMID- 1436975 TI - Healon Yellow as a surgical tool in maneuvering intraocular tissues. AB - Tinted sodium hyaluronate (Healon Yellow) was used during posterior segment surgery mainly for the dissection of epiretinal membranes in cases of proliferative diabetic retinopathy and macular pucker. The yellow color facilitated injecting the viscoelastic substance under the membranes and simplified its removal at the end of surgery. PMID- 1436976 TI - A new tantalum clip for securing a silicone encircling band. PMID- 1436977 TI - The decline of medicine. PMID- 1436978 TI - Visual acuity recovery in cystoid macular edema. PMID- 1436979 TI - Subconjunctival gentamicin induction of extraocular toxic muscle myopathy. AB - Subconjunctival injection of commercially available gentamicin, delivered in one of several protocols, caused an acute toxic reaction myopathy of the extraocular muscles. The response began as a small focal infiltrate of polymorphonuclear leukocytes, and as the lesion progressed it assumed a mononuclear cell predominance accompanied by muscle fiber degeneration. The injection of individual components of the commercial preparation (gentamicin, methylparaben, ethylenediaminetetraacetic acid (EDTA) and sodium bisulfite), each at the same concentration as in the parent solution, gave no response except for gentamicin alone. Gentamicin caused acute toxic myopathy when injected away from the muscles and when given as an isotonic solution in saline compared to the hypotonic commercial solution. Solutions at acidic pH not containing gentamicin did not initiate myopathy. Several factors that have been inferred as participating in the toxic response to gentamicin have been eliminated. Gentamicin alone is responsible for the induction of the extraocular muscle myopathy. PMID- 1436980 TI - Ibudilast may improve retinal circulation in patients with diabetes mellitus. AB - Ibudilast selectively vasodilates cerebral vessels without reducing blood pressure. We investigated the effect of the drug on retinal circulation in 8 patients with diabetes mellitus, using the video-densitometric image analysis of fluorescein angiography. We compared the build up time, the time constant of washout rate and the mean circulation time (MCT) before and after oral therapy with ibudilast. After 2 weeks of daily administration (30 mg), MCT was shortened significantly (4.2 +/- 2.8 vs. 3.0 +/- 1.6 s, p = 0.0215). Since retinal circulation in patients with diabetes mellitus was improved by ibudilast, the drug may be useful to treat disorders such as diabetic retinopathy. PMID- 1436981 TI - Retinal pigment epithelial cells secrete urokinase-type plasminogen activator and its inhibitor PAI-1. AB - Secretion of plasminogen activators and their inhibitors was examined in cultures of human retinal pigment epithelial (RPE) cells. The methods employed were zymography and reverse zymography, solid-phase immunocapture assay, metabolic labeling followed by immunoprecipitation, and immunofluorescence. The results showed that these cells produce urokinase-type plasminogen activator (u-PA) and a plasminogen activator inhibitor (PAI) which is immunologically and biochemically similar to PAI-1. Tissue-type plasminogen activator activity (t-PA) was not detected, but we detected small amounts of t-PA in an inactive complex with inhibitor in RPE cell-conditioned media. We conclude that RPE cells have the potential to utilize u-PA-catalyzed plasminogen activation which is subject to regulation by PAI-1. These results may have a bearing on the pathogenesis of proliferative retinal diseases. PMID- 1436982 TI - X-ray induced DNA strand break induction and rejoining in cultured bovine lens epithelial cells. AB - DNA strand break induction and rejoining in cultured bovine lens epithelial cells were measured by the alkaline unwinding technique followed by hydroxyapatite chromatography. DNA damage is described in terms of dose effect curves for unwinding immediately after irradiation (0 min) and for unwinding after a recovery period (30 min). The dose effect curves obtained are purely exponential with D0 values of 29.3 Gy (0 min) and 138 Gy (30 min), respectively. Rejoining data are given in terms of rejoining enhancement curves with half-times for overall rejoining being in the range from 4 to 10 min, independent of the dose. Kinetics of strand breaks are also presented in terms of decay curves, which are best described by the sum of three exponential components. The half-times of these components have been determined as tau(I) approximately 2 min, tau(II) approximately 15 min and tau(III) approximately 500 min. These components of damage decay curves are discussed in relation to cell killing. PMID- 1436983 TI - Distribution of glucose and lactate in the interphotoreceptor matrix. AB - The photoreceptor cells of the retina derive their nourishment from the choroidal blood supply behind the retina. If the extracellular interphotoreceptor matrix (IPM) mediates this retinal nutrition, then gradients in concentrations of nutrients such as glucose and waste products such as lactic acid would be expected across the IPM, from the neural retina to the retinal pigment epithelium (RPE); this hypothesis is examined here. Gentle methods were employed to prepare IPM from the retinal surface (IPM-R) and apical RPE surface (IPM-P) of bovine eyes, and contamination from adjacent tissues was very low. The actual intrinsic volumes of the IPM-R (180 microliters) and IPM-P (87 microliters) compartments were estimated from dilution of trypan blue dye added to the wash buffer used for sample preparation; these measurements were required for calculation of concentrations. In the IPM-R samples glucose was virtually undetectable and the lactate concentration was very high (13 mM). Near the RPE surface (IPM-P) both compounds were present at levels (glucose 0.9 mM, lactate 3.8 mM) more comparable to those in blood serum. Similar results were obtained with fresh rabbit eyes. This difference in distribution (nutrient more concentrated near RPE, waste product near retina) indicates gradients consistent with the utilization of the IPM as a pathway for outer-retinal nutrition. PMID- 1436984 TI - Laser trabeculostimulation in open-angle glaucoma: a new trial. Part I. AB - We describe herein a new trial to stimulate trabecular meshwork tissue and thereby increase outflow facility. The efficacy of our laser trabeculostimulation (LTS) was compared with that of conventional laser trabeculoplasty (LTP), since LTP causes shrinkage and cicatrization of the meshwork tissue, thus limiting the reduction of postoperative intraocular pressure (IOP). The mean preoperative IOP of 40 eyes was 24.9 +/- 6.8 mm Hg (mean +/- SD). LTS was applied with a 50 microns spot, a power setting of 50 mW and an exposure time of 1 s. With LTS, the IOP decreased but then increased afterward. Results indicate that low power (50 mW) is effective if used for a longer duration. Our LTS can be applied repeatedly and used in addition to conventional LTP. Although our LTS was less effective than LTP, the trial may lead to the development of another useful treatment modality. PMID- 1436985 TI - Bilateral metastatic sclerochoroidal calcification in a patient with hyperparathyroidism. AB - We present the case of a 39-year-old man with bilateral sclerochoroidal calcification with primary hyperparathyroidism. Both the calcium and parathyroid hormone levels were elevated. Funduscopic examination revealed slightly elevated, multiple yellow lesions in both eyes. Fluorescein angiography showed filling defects of the choroid. Ultrasonography showed elevated, highly reflective lesions, and a computed tomography scan of the globe disclosed sclerochoroidal lesions with high density. We discuss the mechanism of sclerochoroidal calcification. PMID- 1436986 TI - Argon laser photocoagulation for the treatment of diabetic macular oedema. Comparative study of efficacy between focal extramacular treatment and focal macular perifoveolar treatment. AB - In this paper a comparative study of efficacy between focal extramacular and focal macular perifoveolar argon laser photocoagulation for the treatment of diabetic macular oedema is presented. The follow-up period was 12 months and was based on fluorescein angiograms. After focal extramacular treatment, diabetic macular oedema was resorbed in 54.6% of the cases, remained unchanged in 28.4% and deteriorated in 17.0%. After focal macular perifoveolar treatment resorption of diabetic macular oedema was achieved in 73.7% of the cases, remained unchanged in 17.1% and deteriorated in 9.2%. Focal macular perifoveolar treatment gives statistically significantly better clinical results than focal extramacular treatment (p < 0.05). PMID- 1436987 TI - [Semiconducting lasers for the treatment of vascular retinopathy]. AB - Clinical photocoagulation was performed successfully in 18 eyes with retinal vascular disease. In all cases semiconductor laser was used emitting wave lengths from 780 to 840 nm. Energy for visible coagulation edema was 400 up to 1,200 mW, time between 0.2 and 1 s. In 3 cases using endolaser, acute retinal traction during light exposition was seen; retinal hemorrhages occurred in no patient. Four patients complained of moderate to marked pain compared to argon laser treatment. In all cases visible marked retinal scars of therapeutical range were observed. PMID- 1436988 TI - Monozygotic twin brothers with age-related macular degeneration. AB - We report the simultaneous development of exudative macular degeneration in monozygotic twin brothers. This report supports the hypothesis that genetic factors may be implicated in the pathogenesis of age-related macular degeneration. PMID- 1436989 TI - Extraocular muscles in congenital strabismus: muscle fiber and nerve ending ultrastructure according to different regions. AB - The ultrastructure of the extraocular muscles of patients affected by congenital strabismus is not completely known, and the structures responsible of the pathogenesis of this condition are still to be determined. Specimens obtained from patients suffering from congenital strabismus were studied and compared with specimens obtained from patients enucleated for various pathologies and not affected by any disorder in the oculomotor system. The scleral myotendinous junction, where the occurrence of an altered proprioceptive innervation was already reported, was examined, and findings obtained were compared with those observed in the muscle body (venter), where motor innervation is prominent and usually described as normal. Only a small number of damaged muscle fibers was found everywhere. The damage consisted in alterations of both contractile structures and mitochondria and resulted in severer lesions in the scleral myotendinous junction rather than in the muscle body. The normal muscle fibers were innervated by motor nerve endings with normal features and by few altered proprioceptors. The less damaged muscle fibers were innervated by normal motor nerve endings and severely damaged proprioceptors. The most severely damaged muscle fibers did not receive any type of innervation. These data seem to imply that the most important functional alteration in strabismus regards the scleral myotendinous junction. It is the authors' opinion that these findings might have a clinical importance in choosing the treatment to be pursued in patients with a squint. PMID- 1436990 TI - Orbital involvement in Waldenstrom's macroglobulinemia: ultrasound, computed tomography and magnetic resonance findings. AB - A case of orbital involvement in Waldenstrom's macroglobulinemia is presented. Orbital echography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed and revealed a retrobulbar mass of the right orbit. Ultrasonography suggested a lymphoid orbital tumor. A CT scan was nonspecific, but helpful in exactly locating the tumor and excluding bony lesions. Signal intensity patterns of MRI were characterized by a low intensity on T1- and T2 weighted images. A marked enhancement of the tumor was evident after intravenous injection of a paramagnetic contrast agent (gadolinium-DTPA). Although the definite diagnosis could only be established by means of an ultrasound-guided fine-needle aspiration biopsy, MRI in connection with the history of our patient strongly suggested a diagnosis of orbital lymphoma in Waldenstrom's disease. PMID- 1436991 TI - Waardenburg syndrome in Japanese patients. Case reports and literature review. AB - A 3-year-old girl (case 1) had a blue iris and albinotic fundus in the right eye and bilateral deafness. Her 6-month-old sister (case 2) had hypopigmented irides and fundi in both eyes and bilateral deafness. We found that the ratios of interinner canthal distance to interpupillary distance were less than 0.65 in normal Japanese controls. In our patients, these ratios were within the normal range, indicating the absence of dystopia canthorum. After reviewing the recent Japanese literature, we found that the hypopigmented iris and deafness seen in our patients are common in Japanese patients with Waardenburg syndrome. PMID- 1436992 TI - Laser flare-cell meter. PMID- 1436993 TI - Human lens transparence in high-myopic subjects. AB - The possibility of a relation between high myopia and lens opacity was studied. For this research, the Lens Opacity Meter 701 was used. The lens opacity values measured in 91 high-myopic eyes were compared with those measured in a control group of 106 emmetropic eyes. This comparison showed that myopic had always higher lens opacity values than emmetropic ones, and this result was statistically significant after the age of 20. PMID- 1436994 TI - Efficacy and stability of amblyopia therapy. AB - To determine the efficacy and stability of therapy, we reviewed the charts of 64 amblyopes with strabismus and/or anisometropia who had been treated by direct occlusion. For patients aged 7 years or less (N = 39), 90% (35/39) showed some acuity gain, with 69% (27/39) achieving at least a doubling of acuity (0.3 log units). Fifty-four percent obtained 20/40 (6/12) or better after an average treatment period of 3.8 months. Some reduction in visual acuity (VA) subsequently occurred for 75% (24/32) of those patients followed. For patients aged 8 years or more (N = 26), 77% (20/26) showed some acuity gain with 31% (8/26) improving at least 0.3 log units. Twenty-seven percent (7/26) obtained 20/40 (6/12) or better after an average treatment period of 4.2 months, although no patients older than 10 years (N = 13) achieved 20/40 (6/12). Loss of some of the acuity gain subsequently occurred for 67% (12/18) of those followed. These findings indicate that VA can be improved by patching therapy in most patients older than 7 years, but the acuity improvement is somewhat less than in younger patients. At least 67% of all amblyopes followed for 1 year lost some of the acuity gain after cessation of therapy, regardless of the age when treated. As a reduction of the acuity gain is likely to occur within the first year after cessation of therapy, it is recommended that amblyopic patients of all ages be followed at regular intervals. PMID- 1436995 TI - Short-term, low-contrast visual acuity reduction associated with in vivo contact lens drying. AB - Hydrogel contact lens surfaces partially desiccate during extended interblink intervals, producing a microscopically rough and irregular surface that scatters light. Such light scattering could reduce retinal image contrast, elevating thresholds for target perception. To test this idea, we measured low (7%) contrast visual acuity of subjects who wore: (1) hydrogel contact lenses, (2) rigid gas permeable (RGP) lenses, and (3) no contact lenses when the subjects blinked normally and when they suppressed blinking. Acuity thresholds were determined using computer-generated acuity stimuli and a staircase psychophysical procedure. Cessation of blinking resulted in small reductions in low-contrast acuity for subjects wearing RGP lenses (mean loss: 0.1 line) or no lenses (mean loss: 0.3 lines). Subjects wearing hydrogel lenses, however, generally exhibited substantial reduction of acuity (mean loss: 4.1 lines) when blinking was suppressed. PMID- 1436996 TI - Role of visual acuity, stereoacuity, and ocular dominance in monovision patient success. AB - Monovision (MV) contact lens correction of presbyopia induces substantial reductions in stereoacuity and small reductions in binocular visual acuity (VA). This study examined those effects in a group of successful and a group of unsuccessful MV patients. Compared to performance with a full binocular correction, the unsuccessful group demonstrated significant losses in both functions. These reductions were smaller in the successful group and of marginal statistical significance only for stereoacuity. Laterality of sighting dominance and laterality of distance/near correction had minimal effect on the results. PMID- 1436997 TI - Set shot shooting performance and visual acuity in basketball. AB - Common sense suggests that decreasing visual acuity will have a negative effect on basketball shooting performance. To test the hypothesis that basketball shooting performance monotonically decreases with decreasing acuity, 19 subjects attempted 25 set shots from a fixed location at each of 5 different acuity levels: 6/6 or better and vision blurred (by optical defocus) to visual acuities of 6/12, 6/24, 6/48, and 6/75. Our results revealed a small but statistically nonsignificant decrease in shooting performance between the 6/6+ and 6/12 conditions. For visual acuities between 6/12 and 6/75, the number of baskets made remained constant. We conclude that decreases in visual acuity over the range of 6/6+ to 6/75 resulting from defocus do not significantly reduce set shot shooting performance. PMID- 1436998 TI - To use or not to use the refractive correction along with hand-held magnifiers. AB - Equivalent viewing power (EVP), field of view, and working distance (WD) were calculated for 4 different magnifier equivalent powers, four magnifier-to-eye distances, and for uncorrected spherical ametropias varying from +20.00 to -20.00 D in 0.25 D steps. Results show that the various viewing conditions which arise (depending on whether or not the refractive correction is worn) can differ considerably. The uncorrected unaccommodating myope has a greater EVP than the equivalent power of the magnifier if he chooses a magnifier-to-eye distance shorter than the focal length of the magnifier. In this situation, field of view is also enhanced. The uncorrected unaccommodating hyperope using a magnifier-to eye distance longer than the focal length of the magnifier achieves a stronger EVP than the equivalent power of the magnifier. However, field of view is then reduced. For the uncorrected unaccommodating spherical ametrope, the use of a magnifier-to-eye distance corresponding to the focal length of the magnifier seems to be a good compromise between EVP, field of view, and working distance. PMID- 1436999 TI - Re-evaluation of the four prism diopter base-out test. AB - The four prism diopter base-out (4 delta BO) test is often recommended for use as an objective assessment of binocular visual function in patients with suspected microstrabismus or central suppression; however, many aspects of the test are unknown. In this series of investigations we evaluated: (1) inter-observer agreement between 2 examiners, using 15 subjects; (2) types of eye movements made and prevalence of the various response types demonstrated in 212 children and 116 adults with normal binocular vision, and 10 children and 4 adults with abnormal binocular vision; and (3) repeatability of test results for 22 subjects evaluated on two separate occasions. In addition, using an SRI Eye-tracker, we documented the eye movements made while testing 2 subjects with small angle strabismus and 4 subjects with normal binocular vision. We found the following results: (1) inter observer agreement is high; (2) both children and adults exhibit many atypical responses, whether or not they have normal binocular vision; (3) diplopia awareness does not differentiate between subjects with normal and abnormal binocular vision; and (4) 4 delta BO test results are not repeatable. Due to frequent atypical and variable responses in subjects with or without normal binocular vision, we suggest the examiner use caution when making a diagnosis based solely on the 4 delta BO test. PMID- 1437000 TI - Joint distribution of sphere, cylinder, and axis. AB - A mathematical expression for the joint probability density function of sphere, cylinder, and axis is presented for the first time. It holds under certain circumstances. A relation is derived which may be useful in obtaining the joint probability function when that expression does not hold. The joint probability density function is of fundamental importance in all quantitative studies of dioptric power in the form sphere, cylinder, and axis. Some of its properties are described. It represents a hypersurface in a four-dimensional space with a maximum, a saddle point, and variety of ridges. PMID- 1437001 TI - Eye position and head size in the Chinese population: a comparison of the Chinese from Hong Kong with the Chinese from Guangdong Province. AB - Measurements obtained in this study include facial and head dimensions. From our findings, it would appear that the Chinese population in Hong Kong have not become different in the two or three generations that separate them from those living in Guangdong province of China. PMID- 1437002 TI - Chromatic aberration and optical power of a diffractive bifocal contact lens. AB - Although diffractive contact lenses have been well documented in theory, no definitive experimental data have been reported which confirm that the near image is in fact created by diffraction rather than by refraction. We have tested the diffraction hypothesis for one type of diffractive contact lens (the Hydron Echelon bifocal) experimentally by measuring its longitudinal chromatic aberration in isolation and when worn on the eye. The basis of this test is that, according to theory, diffractive lenses should have chromatic aberration which is opposite in sign to that measured for the eye. Objective measurements of chromatic aberration were made with a focimeter when the lens was in a wet cell. Subjective measurements were made with a Badal optometer when the lens was worn on the eye. Four control experiments were conducted to provide baseline measurements of the eye's chromatic aberration, against which we compared the results obtained for the diffractive contact lens. The data were also compared with conventional measurements of refractive error obtained by standard subjective techniques and by an automated infrared refractor. Our results showed that the longitudinal chromatic aberration of the diffraction image of the Echelon bifocal lens was about one-half that obtained under the four control conditions: for the naked eye, for the nondiffraction image of the Echelon lens, or for either image of a refractive bifocal contact lens (CIBA Bisoft). These results are consistent with the theoretical prediction that the negative chromatic aberration of a diffractive contact lens should partially cancel the positive chromatic aberration of the human eye.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437003 TI - Equivalent oxygen percentage as a function of hydration in hydrogel lenses: an in vivo study. AB - Although many investigations have examined the parameters of hydrogel lens hydration loss, the in vivo effect (in humans) on lens oxygen behavior has not been characterized previously. Human subjects wore 2 different lenses (a thin, 38% water polymacon lens and a thin, 55% water bufilcon lens) for 5-min periods under either fully hydrated (i.e., with saline regularly applied to the lens) or partially hydrated (i.e., with "normal" wear of 1 blink every 5 s) conditions. An equivalent oxygen percentage (EOP) technique and a gravimetric method were used to determine lens oxygen behavior and hydration, respectively. The hydration results demonstrate that significant lens dehydration occurs during the partially hydrated (normal blink rate) condition compared to the in situ, fully hydrated situation. A corresponding, statistically significant diminution in oxygen equivalency was also observed. PMID- 1437004 TI - Ocular manifestations of chronic fatigue and immune dysfunction syndrome. AB - Chronic fatigue and immune dysfunction syndrome (CFIDS) is a disease presenting with systemic, sensory, cognitive, and psychological manifestations. Ocular symptomatology is reported in the visual, functional, perceptual, and pathological aspects of the visual system. The purpose of the research was to evaluate ocular symptoms in patients with CFIDS. One hundred and ninety CFIDS patients [155 females, 35 males; mean age of 41 years (range 15 to 72)] and 198 healthy controls [133 females, 65 males; mean age of 42 years (range 8 to 89)] were surveyed via written questionnaire. Evaluation of data showed statistical significance at levels ranging from 0.0001 to 0.007 for all but one symptom surveyed. It appears that the ocular symptoms of CFIDS are genuine. Further research is needed to determine the etiology and appropriate treatment of this disease. PMID- 1437005 TI - Optometry research. Part 2: Grants received. AB - Part 1 showed that the dominant provider of ophthalmic research funding (85%) was the National Eye Institute (NEI) and that on the average optometry faculty members had received about 3% of that funding over the years. Part 2 shows how this 3% of NEI funding has been distributed among the 16 U.S. schools in existence during the period studied and why 3% is a rational result under current conditions. PMID- 1437006 TI - Protanomals and deuteranomals. PMID- 1437007 TI - Effect of storage time with different lens care systems on in-office hydrogel trial lens disinfection efficacy: a multi-center study. AB - A combined prospective and retrospective study was conducted to evaluate the efficacy of in-office disinfection methods for hydrogel trial contact lenses. Two hundred and twenty-one trial contact lenses, disinfected by four different disinfection methods, were collected from seven Study Centers and cultured for microbial contamination after various storage periods. Negative and positive control lenses were included as an additional Center in this double-masked study. There was a significant difference in the incidence of microbial contamination among the Centers for all storage times (chi 2 p < 0.001). Contamination of trial lenses in Centers using thermal disinfection with preserved saline (SoftWear Saline) was negative and thermal disinfection with nonpreserved saline (LensPlus Saline) was 8.7%. Lens contamination in Centers using chemical disinfection was 13.6% with ReNu and 40.7% with OptiFree. The degree of contamination ranged from 90 colony forming units (CFU)/ml to over 10 million CFU/ml. Among the microorganisms isolated after the different disinfection methods were Alcaligenes xylosoxidans, Serratia marcescens, Moraxella phenylpyruvica, Enterobacter agglomerans, Pseudomonas stutzeri, and various gram-positive organisms. This study suggests that practitioners should redisinfect all inventory trial lenses at least once a month to minimize the risk of patient infection. PMID- 1437008 TI - True and apparent oxygen permeabilities of contact lenses. AB - We studied the passage of oxygen through some commercially available contact lenses. Oxygen diffusion coefficients were determined by the time-lag method and a 201T Redher permeometer was used to measure the oxygen permeability and transmissibility by the polarographic method. The measurements were carried out at room temperature with 0.09% sodium chloride physiologic solution. The following types of lenses were tested: (1) 12 lenses of cellulose acetate butyrate (CAB) of a mean thickness of 0.194 mm (observed Dk approximately 6.3 barrers) (1 barrier is equivalent to 10(-11) cm3 of O2 (STP).cm2/cm3.s.mm Hg). (2) 13 lenses of a cross-linked polyhydroxyethyl methacrylate (2-HEMA), manufactured by Lenticon and Bausch & Lomb, with 40 and 38.6% water content, respectively. The mean thicknesses were 0.160 and 0.148 mm, respectively (observed Dk approximately 12 to 13.5 barrers). (3) Finally 10 lenses of a copolymer of 2 HEMA with N-2-vinylpyrrolidone (2-HEMA/VP), manufactured by Bausch & Lomb under the name Hydrocurve II, with 55% water content and a mean thickness of 0.138 mm (observed Dk approximately 24.5 barrers). For a given lens thickness, the transmissibility and permeability of lenses whose main material is 2-HEMA are found to be equivalent. This fact suggests the use of such material as a standard in the study of diffusion processes in contact lenses of low oxygen permeability (Dk approximately 12 to 13.5 barrers). We studied the boundary layer effects and found significant discrepancies between true and apparent oxygen permeabilities. The apparent transmissibility decreased with increasing lens thickness, this effect being more apparent for lenses with low water content. Oxygen permeability is found to be exponentially dependent on water content rather than on the chemical composition of the hydrogel. PMID- 1437009 TI - Influence of power changes in single cut rigid contact lenses on tear pump efficiency. AB - Differences between corneal oxygen uptake rates measured after 5 min of static (without blinking) and 5 min of dynamic (with blinking once every 5 s) non-gas permeable (polymethyl methacrylate) contact lens wear, referenced to the oxygen uptake rates of the normal open eye, were used as indications of tear pump efficiencies associated with each of seven contact lens back vertex powers (-9.00 to +9.00 D, in 3.00 D steps). Measurements were made in vivo on six human corneas showing with-the-rule (0.25 to 0.87 D) toricity. Lens overall diameter was 8.8 mm, optic zone diameter was 7.4 mm, and base curve radius was fitted "on K." Lens center thickness was 0.14 mm for all minus-powered lenses, and 0.19, 0.26, 0.34, and 0.41 mm for the plano, +3.00, +6.00, and +9.00 D lenses, respectively, maintaining an edge thickness of 0.11 mm. Under both static and dynamic wearing conditions, no significant differences were found among the corneal oxygen uptake rates associated with the various contact lens back vertex powers; however, the difference between the static and dynamic condition data, an indication of tear pump efficiency, was greatest for the -3.00 D lens. The difference values associated with the +9.00 and +6.00 D lenses were significantly lower than those associated with the minus power lenses. PMID- 1437010 TI - Shape of the myopic eye as seen with high-resolution magnetic resonance imaging. AB - We have obtained multislice magnetic resonance (MR) images of the eye and calculated ocular dimensions along the three cardinal axes: antero-posterior (A P), equatorial, and vertical. We found no difference in the shape of hyperopic (average refractive error: +3.72 D) and emmetropic eyes, both of which had an equatorial diameter longer than the A-P and vertical diameters. Myopic eyes (average refractive error: -6.54 D) were larger than hyperopic eyes, and most had the same spheroelliptical shape as that of the emmetropic and hyperopic eyes. The results suggest that during myopic progression an overall enlargement or a radial volume expansion has occurred. PMID- 1437011 TI - An innovative solution to continuing misuse of red light on automobiles. AB - A novel approach [referred to as the RLMS (Red Light Means Stop) approach] to automotive rear lighting has recently been suggested as a means to enhance perceptibility of the rear lights. In the RLMS approach, only red colored light is displayed during braking, and only amber colored light is displayed at other times. Color per se then provides, for most drivers, an immediately perceptible visual stimulus by which brake lights are distinguished from tail lights. In earlier testing, simultaneous display of nonred tail lights and red brake lights confronted test subjects with antagonistic visual stimuli, thereby compromising, and underutilizing, the value of color. It is suggested that the potential safety value of the RLMS approach is significant, and that comprehensive testing should be conducted in a timely manner. PMID- 1437012 TI - Evaluation of intraocular pressure in a pediatric population. AB - The purpose of this study was to examine the intraocular pressure (IOP) in a pediatric population without general anesthesia, and compare it to the IOP in a normal adult population. Little information is available on the normal IOP in a pediatric population. IOP was measured in a sample of 212 eyes (111 patients) using the Keeler Pulsair Hand Held Non-Contact Tonometer to determine the range of IOP in this population. Patients ranged in age from 7 months to 5 years, 10 months. The mean IOP of each eye was based on three readings. These IOP values were grouped by the chronological age of the children. The results support the conclusion that infant/toddler patients have lower mean IOP than adults and that as age increases, IOP increases. PMID- 1437013 TI - Asthenopia induced by computer-generated fusional vergence targets. AB - A questionnaire was used to evaluate asthenopia in 30 normal subjects (Ss). Then, each S experienced 3 min of continuous alternating convergent and divergent fusional vergence or a control condition which was identical to the experimental condition, but without any vergence demand, i.e., version. The stimulus was a computer-generated flat fusion red-blue anaglyph picture of a horse. The order of vergence and version conditions were randomized. Asthenopia measures and maximal fusional vergence ranges measures were repeated immediately after each condition. Results indicated a significantly higher rating of asthenopia after induced vergence than version. There were no differences in maximal fusional vergence ranges or recovery values after the two conditions. Correlations between pretreatment asthenopia scores and asthenopia scores after either induced vergence or version were also not significant. Post hoc analyses of Ss grouped as having either high or low asthenopia, according to baseline ratings, revealed no significant differences in vergence or version conditions. Alternative hypotheses for these results are presented. PMID- 1437014 TI - Determination of the true size of an object on the fundus of the living eye. By H. Littmann from the original article, "Zur Bestimmung der wahren Grosse eines Objektes auf dem Hintergrund des lebenden Auges," which originally appeared in Klinisches Monatsblatter fur Augenheilkunde 1982; 180:286-9. Translated by TD Williams. PMID- 1437015 TI - Traumatic avulsion of the optic nerve. AB - Avulsion of the optic nerve is an infrequent traumatic event which results in a permanent and usually devastating loss of vision. We present two cases which highlight the salient features of partial and complete optic nerve avulsion. The clinical findings, including the results of B-scan ultrasonography, fluorescein angiography, and computed tomography (CT) are discussed. In addition, the past two decades of literature pertaining to optic nerve avulsion are reviewed and summarized. PMID- 1437016 TI - Optometry research. Part 1: Funding sources. AB - Part 1 of this report presents an overview of U.S. ophthalmic research in general and of optometry research in particular and identifies the National Eye Institute (NEI) as the dominant funder of both types of research. Part 2 examines how NEI funding has been distributed among the U.S. schools and colleges of optometry in the past, whereas Part 3 examines the production of published research from the schools and colleges and the Department of Veterans Affairs Optometry Service. Information is presented to indicate that the schools of optometry account for about 3% of all NEI funding and produce about 3% of all published ophthalmic research. Published optometry research results mainly from the activities of four schools and the VA Optometry Service, which has rapidly become the leading source of articles published in The Journal of the American Optometric Association and presenter of continuing education at the Academy's annual Ellerbrock Lectures. This study suggests optometry needs to husband its relatively small research base and, in the author's opinion, concentrate on the support of clinical trials and research directly relevant to primary eye care rather than basic biologic or physiologic research. PMID- 1437017 TI - Factors influencing hand/eye synchronicity in the computer age. AB - In using a computer, the relation of vision to hand/finger actuated keyboard usage in performing fine motor-coordinated functions is influenced by the physical location, size, and collective placement of the keys. Traditional nonprehensile flat/rectangular keyboard applications usually require a high and nearly constant level of visual attention. Biometrically shaped keyboards would allow for prehensile hand-posturing, thus affording better tactile familiarity with the keys, requiring less intense and less constant level of visual attention to the task, and providing a greater measure of freedom from having to visualize the key(s). Workpace and related physiological changes, aging, onset of monocularization (intermittent lapsing of binocularity for near vision) that accompanies presbyopia, tool colors, and background contrast are factors affecting constancy of visual attention to task performance. Capitas extension, excessive excyclotorsion, and repetitive strain injuries (such as carpal tunnel syndrome) are common and debilitating concomitants to computer usage. These problems can be remedied by improved keyboard design. The salutary role of mnemonics in minimizing visual dependency is discussed. PMID- 1437018 TI - Scanning electron microscopy of the mucosal surface of the forestomachs and abomasa of grey, white and black Karakul lambs. AB - Homozygous grey and white Karakul lambs suffer from a lethal genetic factor causing death after weaning. Previous studies revealed large milk-filled rumens in the grey and white lambs which was attributed to a significant decrease in the number of myenteric ganglia and neurons in the rumen wall. This study was undertaken to determine the effect of milk on the epithelial lining of the forestomachs of affected grey and white lambs. In the forestomachs of the black lambs the polygonal epithelial cells were tightly packed, seemed to overlie one another and cytoplasmic projections occurred on the cell surfaces. In the grey and white lambs the epithelium had an eroded appearance due to sloughing of the surface cells and the cytoplasmic projections were lower and had a weathered appearance compared to the black lambs. No obvious differences could be detected in the abomasa of grey, white and black lambs. It is concluded that the milk in the forestomachs of the grey and white lambs is responsible for the epithelial changes. PMID- 1437019 TI - Parasites of South African wildlife. XIII. Helminths of grey rhebuck, Pelea capreolus, and of bontebok, Damaliscus dorcas dorcas, in the Bontebok National Park. AB - A total of 25 grey rhebuck, Pelea capreolus, and 16 bontebok, Damaliscus dorcas dorcas, were shot for parasite recovery at bi-monthly intervals in the Bontebok National Park, south-western Cape Province, from February 1983 to December 1983 and February 1983 to February 1984, respectively. The grey rhebuck and the bontebok each harboured 9 nematode species and the latter animals 1 cestode species. Ostertagia hamata was most abundant and most prevalent in the grey rhebuck and Longistrongylus curvispiculum and Nematodirus spathiger in the bontebok. Longistrongylus schrenki is recorded for the first time in grey rhebuck, and Trichostrongylus falculatus and Moniezia expansa in bontebok. The total nematode burdens of the bontebok were considerably larger than those of the grey rhebuck. No clear pattern of seasonal abundance for the helminths of either host species was evident. PMID- 1437020 TI - Subsampling of large light trap catches of Culicoides (Diptera: Ceratopogonidae). AB - Analyses of 2 light trap catches comprising 6,041 and 1,598 Culicoides showed that the reliability of subsampling such catches increased with subsample size, while the subsampling error decreased with an increase in the number of individuals per species present in a subsample. Subsamples comprising approximately 500 Culicoides are deemed sufficient for comparing population densities between sites and sampling occasions and also give an acceptable indication of relative species abundance at a site. It is recommended that species for which the mean number of specimens in subsamples originating from 3 catches at a site is less than 7, should not be included in biometric analyses aimed at comparisons of population densities. For all other species a test level of 1% rather than 5% should be used for such comparisons. When species ratios obtained from subsampled catches are employed as indicators of abundance, the chi squared test should be utilized at a 1% level if the ratios originate from 3 catches at a site and at a 0.1% level if only one catch per site is made. Due to poor representativeness of small catches, it is suggested that species for which fewer than 7 individuals are present in a single subsample, be excluded from chi squared tests. A 5-point procedure for subsampling a large light trap collection of Culicoides is given. PMID- 1437021 TI - Evaluation of the efficacy of d-penicillamine and trientine as copper chelators using an in vitro technique involving ovine red blood cells. AB - An in vitro technique for haemolysing ovine red blood cells with copper sulphate was standardized to induce c 50% haemolysis with 0.5 mM CuSO4 after incubation for 14 h at 38 degrees C. This technique was then applied to test the efficacy of trientine and d-penicillamine in preventing haemolysis. Trientine concentrations of 0.5; 1.0 and 1.5 mM were found to be the most effective (P < 0.05) in reducing copper-induced haemolysis. One and 1.5 mM concentrations of d-penicillamine were also effective (P < 0.05), but in this experiment a 0.5 mM concentration failed to protect the erythrocytes. PMID- 1437022 TI - A survey of small stock tick control practices in the eastern Cape Province of South Africa. AB - Current small stock tick control practices and producer attitudes towards tick control in the eastern Cape Province of South Africa are discussed. These were ascertained from returns to a questionnaire survey to which 31.2% of farmers polled, responded. In general, producers did not favour an intensive tick control policy for small stock. Angora, mutton and wool farmers had a definite preference for synthetic pyrethroid acaricides, the majority treating either less than 6 times p.a. or between 11-15 times p.a. Most producers changed acaricides because of price. All small stock producers favoured plunge dip application of acaricides while the majority of wool sheep and Angora producers utilized footbath application as a second preference. Mutton producers favoured pour-on and hand spray application as a second choice. Producers who used plunge dip application techniques experienced the highest percentage of confirmed acaricide resistance which is in accordance with application preference. The general incidence of confirmed acaricide resistance, however, was of a low order but highest amongst mutton farmers. An average cost for acaricide treatment of R1.65 per small stock unit p.a. was calculated from data gained in this survey. Only a small number of producers used the available heartwater vaccine. Small stock mortalities experienced by producers per production unit indicated higher mortalities at high acaricidal treatment frequencies. Farmers allowing a small number of ticks to infest their sheep experienced fewer mortalities due to heartwater than those than kept their sheep free of ticks. Angora goat farmers experienced the same, but with higher mortalities, probably due to the apparently high susceptibility of Angora goats to heartwater. PMID- 1437023 TI - A survey of cattle tick control practices in the eastern Cape Province of South Africa. AB - Current cattle tick control practices and producer attitudes towards tick control in the eastern Cape Province of South Africa are discussed. These were ascertained from answers to a questionnaire survey to which 31.2% of farmers responded. In general, producers favoured intensive tick control. Beef and dairy farmers had a definite preference for synthetic pyrethroid acaricides, the majority followed a 25 times p.a. treatment frequency and most changed acaricides because of price. Beef producers favoured pour-on application of acaricides while the majority of dairy producers utilized plunge dipping. Producers who used hand spray techniques experienced the highest percentage of confirmed acaricide resistance. A costs of R11.27 for acaricide treatment per bovine per annum was calculated from data gained in this survey. A cost index of 2,496 was calculated by relating acaricide cost to the prevailing price of beef in the region. Only a small number of producers used heartwater, babesiosis and anaplasmosis vaccines. Relative tick borne disease mortality ratios indicated higher heartwater mortalities at high acaricide treatment frequencies. These results are discussed in relation to the tick control regimes practised. PMID- 1437024 TI - Deep dissections of the veins of the bovine head: unpublished work by Prof. J. M. W. Le Roux (1926-1991). PMID- 1437025 TI - The transovarial transmission of Babesia trautmanni by Rhipicephalus simus to domestic pigs. AB - Rhipicephalus simus was, for the first time, experimentally proven to be a transovarial vector of Babesia trautmanni of domestic pigs. The nymphal and adult progeny of experimentally infected female ticks transmitted the infection to 2 susceptible splenectomized pigs. Features of the infection included a prepatent period of 6-8 days post-tick infestation, a febrile reaction for 3 days and a maximum parasitaemia score of 15 (more than 6 parasites per 300 red blood cells). Other clinical signs in both pigs were mild inappetence and listlessness. Both pigs recovered without any antibabesial therapy. PMID- 1437026 TI - No serological evidence for the presence of swine vesicular disease virus in South Africa. AB - An indirect ELISA incorporating a protein A-peroxidase conjugate was developed for detecting antibodies to swine vesicular disease virus (SVDV) in pig sera. This test and a conventional virus neutralization test were found to be equally sensitive. A total of 2846 pig sera collected from various abattoirs in South Africa were tested using the indirect ELISA. No serological evidence of infection with SVDV in pigs in South Africa was found. PMID- 1437027 TI - A comparative study of the thickness of the tunica muscularis in the forestomach and abomasum of grey, white and black Karakul lambs. AB - Homozygous grey Karakul lambs are born with a lethal genetic factor responsible for death and weaning age. When put on a high roughage diet under field conditions they develop distended, thin-walled rumens and sand impacted abomasa. Homozygous white Karakul lambs have a similar factor but survive for a longer period. Black Karakul lambs are not affected. The present study was undertaken to compare by image analysis the thickness of the tunica muscularis of the forestomach and abomasum of 24-hour old grey, white and black Karakul lambs. One square centimetre samples were taken from equivalent areas in each case of the rumen, reticulum, omasum and abomasum of 38 embalmed Karakul lambs. Haematoxylin and eosin stained histological sections of each sample were studied with a Vids 2 Image Analyzer and the thickness of the circular and longitudinal muscle layers was measured. An analysis of variance indicated a significant difference between the groups in the thickness of the tunica muscularis of the rumen, reticulum and abomasum; the grey group displaying the thinnest and the black group the thickest. The omasa were not affected. The study indicates a reduction in thickness of the tunica muscularis of the homozygous grey and white lambs when compared to normal black lambs. PMID- 1437028 TI - Temporomandibular joint: surgically created disk displacement causes arthrosis in the rabbit. AB - To document a causal relationship between temporomandibular joint disk displacement and arthrosis, the disk was surgically displaced in one temporomandibular joint in each of three rabbits. The rabbits were sacrificed after 4 weeks and the mandibular condyles were studied radiographically and histologically. All three joints that underwent disk displacement had radiographic and histologic evidence of arthrosis, which included erosion of the bone, irregularity and fissure formation of the articular soft tissue cover, disruption of the subchondral layer of cartilage cells, and chondrocyte proliferation. No radiographic or histologic changes occurred in the joints that were untouched. The results suggest that surgically created disk displacement can cause arthrosis in the temporomandibular joint of the rabbit. PMID- 1437029 TI - Cryosurgical treatment of hemangiomas of the lip. AB - Removal of hemangiomas presents difficult management problems. This article describes the treatment of hemangiomas of the lip by cryosurgery and, in particular, evaluates the effectiveness of freezing in nitrous oxide cryosurgery on these lesions. Four women and two men, ages 40 to 76 years and manifesting angiomatous lesions on the vermillion of the lower or upper lips, were treated. Each site was directly exposed to two consecutive freeze-thaw cycles of 40 seconds freezing time at -30 degrees C to -40 degrees C. No anesthesia was required. Healing was uneventful. Superficial necrotic tissue covered the lesion at 1 week and necrotic slough was separated after 2 to 4 weeks, leaving a fully epithelialized surface. In all cases, there was no scarring and no recurrence was noted during the 2.5 year follow-up. PMID- 1437030 TI - Temporomandibular joint disk displacement without reduction. Treatment with flat occlusal splint versus no treatment. AB - A flat occlusal splint has been extensively used in the treatment of patients with temporomandibular joint disk displacement without reduction, but no studies with untreated controls have assessed its effect. We randomly assigned 51 patients with temporomandibular joint pain and arthrographically verified disk displacement without reduction to be treated with a flat occlusal splint or to serve as untreated control subjects in a 12-month clinical trial. Pain symptoms disappeared in about one third of the patients in each group. Another third of the patients in the control group improved. Sixteen percent of the patients in the control group and 40% of the patients treated with a flat occlusal splint were worse at the end than at the beginning of the study. Joint pain and muscle tenderness decreased more frequently in the nontreatment controls than in the treatment group. A statistically significant benefit of a flat occlusal splint over nontreatment control subjects could not be identified in this study of patients with painful disk displacement without reduction. The use of a flat occlusal splint in this patient group should therefore be reconsidered. PMID- 1437031 TI - The morbidity associated with fifty maxillary fractures treated by closed reduction. AB - Fifty patients with maxillary fractures treated by closed reduction over an 85 month period at a Level I trauma center were reviewed. Thirty patients (60%) experienced forty-one midfacial complications. The most frequent problems were infraorbital nerve paresthesia (12), enophthalmus (5), septal deviation (3), and altered vision (3). No relationship could be established between complications and age, sex, cause of injury, or the method of suspension used. Most complications were related to concomitant injury or the concurrent management of fractures of other facial bones. Only eight problems (16%) were directly attributed to the closed reduction of maxillary fractures. Patients treated by closed reduction and maxillomandibular fixation without suspension experienced no surgical complications. PMID- 1437032 TI - Maxillary osteomyelitis and spontaneous tooth exfoliation after herpes zoster. AB - Reports of spontaneous tooth exfoliation and osteonecrosis trigeminal herpes zoster are extremely rare and have been sporadic. This article reports a pertinent case of a 50-year-old man who exhibited prodromal odontalgia before the appearance of vesicular mucocutaneous lesions, together with severe destruction of the maxillary bone and exfoliation of multiple teeth. This patient was successfully treated using a unique closed nasal-vestibular drainage system for the ultimate control of maxillary bone viability. A review and analysis of the clinical aspects and the pathogenesis of herpes zoster and bone necrosis are discussed. PMID- 1437033 TI - Traumatically induced peripheral osteoma. Report of a case. AB - Osteomas of the jaws are well-defined lesions that can present as an isolated finding or as part of a syndrome (e.g., Gardner's syndrome). The etiology of peripheral osteomas is somewhat controversial. Trauma has been implicated by several authors, and osteoma is presented here as a rather striking lesion with well-defined traumatic origins. PMID- 1437034 TI - Effects of total body irradiation on salivary gland function and caries associated oral microflora in bone marrow transplant patients. AB - Forty-one cancer patients who received chemoradiotherapy conditioning with bone marrow transplantation were examined for changes in salivary gland function and caries-associated oral microflora. Salivary flow rates (stimulated and unstimulated) and Streptococcus mutans levels decreased after pretransplant cytoreductive therapy and posttransplant prophylactic antibiotic therapy. Normal levels returned with time after the patients left the protected environment. Lactobacillus counts were not affected. Chronic graft-versus-host disease did not significantly influence saliva production. Results indicate that irradiation is probably the major factor responsible for the transient xerostomia. PMID- 1437035 TI - Blood pressure response to routine restorative dental treatment with and without local anesthesia. Continuous noninvasive blood pressure registration with a finger manometer. AB - A continuous noninvasive blood pressure registration with the Finapres finger manometer was carried out during routine dental treatment, with and without local anesthesia. Forty patients (21 male), 21 to 64 years of age, were studied. Blood pressure was recorded continuously from 10 minutes before dental treatment to 10 minutes after treatment was completed. No local anesthetic was used in 25 patients. In 15 patients (seven men) local anesthetic was used. All patients showed a considerable blood pressure variation. During treatment a significant mean blood pressure increase was registered in the patients treated without local anesthesia. In the patients treated with local anesthesia no significant mean blood pressure changes during dental treatment could be established. However, during the actual administration of the local anesthetic solution a transient blood pressure increase was found, followed by a decrease shortly after removal of the needle from the mouth. After treatment of both groups of patients, a mean blood pressure decrease was established. PMID- 1437037 TI - Plasma cell gingivitis. Report of two cases. AB - Plasma cell gingivitis is a disorder first described in the 1960s and was believed to be caused by an allergic reaction to flavored chewing gum and toothpaste. The lesion was believed to have been largely eliminated by removing the allergens from the products. We report two additional cases, not related to a known allergen. One patient was allergy tested thoroughly and given a strict elimination diet without resolution. Immunofluorescence study suggests a reactive rather than a neoplastic process. PMID- 1437036 TI - Efficacy of chlorhexidine and nystatin rinses in prevention of oral complications in leukemia and bone marrow transplantation. AB - The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers. The current randomized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine, nystatin, and saline solution rinses to reduce the findings of oral mucositis, gingivitis, and oral infection. The results of this study did not show a reduction in mucositis with the use of these rinses. However, potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse. PMID- 1437038 TI - Immediate biopsy versus a therapeutic trial in the diagnosis and treatment of vesiculobullous/vesiculoerosive oral lesions. Opposing viewpoints presented. AB - There are at least two treatment strategies in the diagnosis and treatment of oral vesiculobullous/vesiculoerosive disease. The relative merits of immediate biopsy and initial therapeutic trial regimens are debated. PMID- 1437039 TI - Lichenoid lesions of oral mucosa. Diagnostic criteria and their importance in the alleged relationship to oral cancer. AB - Lichen planus and other lichenoid disorders of oral mucosa occur commonly, and yet they are poorly understood. Further, the question of the premalignant potential of oral lichen planus remains deeply mired in controversy. The object of this article is to delineate these problems, clarify the issues, and present evidence to support the position that true lichen planus of oral mucosa is not only less common than generally appreciated but also has no inherent predisposition to become malignant. Rationale and data from the literature are offered in support of this position. PMID- 1437040 TI - The controversy of a premalignant potential of oral lichen planus is over. PMID- 1437041 TI - Diseases should not be considered entities unto themselves. PMID- 1437042 TI - Cinnamon-induced stomatitis venenata, Clinical and characteristic histopathologic features. AB - Fourteen new cases of cinnamon-induced stomatitis are reported. Ten of these fourteen cases were first detected on the basis of histopathologic changes, which included hyperkeratosis, chronic lichenoid mucositis with plasmacytic infiltration, and marked chronic perivasculitis. Six cases of false-positive histopathologic findings are presented for comparison. It is recommended that when the histopathologic features described are recognized, cinnamon stomatitis should be considered. PMID- 1437043 TI - Survey of tissue diagnostic services in U.S. dental schools - 1990. AB - Tissue diagnostic services in U.S. dental schools were surveyed to determine activities during 1990. Results were compared with those of similar surveys conducted in 1953, 1958, 1969, 1975, 1980, and 1985. The information gathered from this survey reveals a progressive growth and development of tissue diagnostic services. This is seen not only in the increased numbers of biopsy accessions, which increased by 37% since the last survey, but is also reflected in the diversity of services now offered by oral pathologists. PMID- 1437044 TI - Oral Geotrichum candidum infection associated with HIV infection. A case report. AB - Infections with Geotrichum species, although rare, are sometimes seen in immunocompromised hosts. We report a case of oral geotrichosis in a patient seropositive for human immunodeficiency virus who had erythematous mandibular and maxillary gingiva but was otherwise free of any active systemic disease. Geotrichum candidum was shown by both culture and histopathology to be present in the lesion and was deduced to be the causative organism. The patient responded well to several weeks of treatment involving oral topical administration of nystatin vaginal tablets. PMID- 1437045 TI - Biologic properties of eugenol and zinc oxide-eugenol. A clinically oriented review. AB - Eugenol-containing dental materials are frequently used in clinical dentistry. When zinc oxide-eugenol (ZOE) is applied to a dentinal cavity, small quantities of eugenol diffuse through the dentin to the pulp. Low concentrations of eugenol exert anti-inflammatory and local anesthetic effects on the dental pulp. Thus use of ZOE temporary filling may facilitate pulpal healing; on the other hand, high eugenol concentrations are cytotoxic. Direct application of eugenol to pulp tissue may result in extensive tissue damage. The ability of ZOE-based endodontic sealers to influence periapical tissue healing is considered in view of eugenol's anti-inflammatory and toxic properties. PMID- 1437046 TI - Biocompatibility of retrograde filling materials in the ferret canine. Amalgam and IRM. AB - Periapical tissue response to retrograde fillings of amalgam and IRM were compared in the mandibular canine of the adult male ferret. Teeth were cleaned and shaped with a standard technique and obturated with gutta-percha. The root apex was then exposed and retrofillings were placed. The animals were grouped according to observation periods of 5, 10, and 15 weeks. At the proper time the animals were killed and the lower canine tooth along with the surrounding bone was removed. The tissue blocks were examined clinically, radiographed, and prepared for histologic examination. The clinical and radiographic examination indicated both materials to be well tolerated by periapical tissues. Microscopic examination of amalgam specimens showed a decrease in inflammation and the formation of a fibrous capsule over the 15-week period. IRM specimens showed persistent inflammation and slower healing potential. PMID- 1437047 TI - Diagnosing periapical bone lesions on radiographs by means of texture analysis. AB - Trabecular pattern, the radiographic projection of trabecular bone, is a repeated structure that appears in a dental radiograph. Texture analysis, the computer image analysis of repeated patterns, is a technique that can be used to automate the diagnosis of periapical lesions with the detection of the absence of the texture that corresponds to the trabecular bone. The purpose of this study was to determine whether it is feasible to use texture analysis to identify the presence of the trabecular pattern in radiographs and to detect a periapical bone lesion based on a local absence of this pattern. Thirty-two mandibular periapical films, 16 with and 16 without periapical lesions, were used in this study. Texture analysis was carried out on the digital images of these radiographs. In the 16 films with lesions, they were all correctly identified, and no lesions were found in the 16 films without lesions. This result is based on the a prior knowledge of the user about the localization of the disease. Locating periapical regions without user interaction is a goal for future research. PMID- 1437048 TI - Quantitative features of digitized radiographic bone profiles. AB - The purpose of this investigation was to examine the use of four image features in describing digitized radiographic bony scan lines, or profiles. These features include the mean pixel intensity, I (x); pixel intensity variance, var I (x); mean absolute Fourier transform coefficient, magnitude of F(u); and mean spatial first moment of the absolute Fourier coefficients, M1. In an animal model I (x) and M1 differed significantly while magnitude of F(u) tended to differ significantly between digitized radiographic profiles of osteoporotic (n = 6) and control (n = 6) rabbit humeri. Case examples illustrating the application of this technique to digitized radiographs of human interproximal alveolar bone are presented. PMID- 1437049 TI - Cementoblastoma in Hong Kong Chinese. A report of four cases. AB - Four cases of cementoblastomas in Hong Kong Chinese are presented, two are classic lesions and two are clinically and radiologically atypical. A summary of the literature is presented in tabular form. PMID- 1437050 TI - Root resorption associated with impacted maxillary third molar. PMID- 1437051 TI - Fusion of third and fourth mandibular molars? PMID- 1437052 TI - Tooth in the sigmoid notch. PMID- 1437053 TI - Infected cyst in the coronoid process. PMID- 1437054 TI - Pulse oximetry during minor oral surgery with and without intravenous sedation. AB - This study investigated the levels of oxygen saturation and pulse rates of patients undergoing minor oral surgery under local analgesia, with (20 patients) or without (20 patients) intravenous sedation with midazolam. The results indicated that a statistically significant fall in arterial blood oxygenation of 1% to 2%, as measured by pulse oximetry, followed midazolam administration; however, this was physiologically insignificant. Both groups showed a similar postoperative small fall in oxygen saturation. Transient episodes (24 to 36 seconds) of physiologically significant mild hypoxia occurred during breath holding, but this condition was readily corrected by encouraging patients to breathe deeply. Midazolam had a small but significant calming effect on the higher preoperative pulse rates exhibited by anxious patients, but this effect was not sustained during the operating period. Both sedated and unsedated patients showed episodes of tachycardia that could have significance for patients with cardiac disease. PMID- 1437055 TI - Hypoglycemia as a possible factor in the induction of vasovagal syncope. AB - Glucose level was estimated in capillary blood of 16 patients, who had vasovagal syncope during exodontia with local anaesthesia. One consistent finding was the low blood sugar level in all patients during syncope, as compared with the level 1 hour after recovery. Hypoglycemia can be induced by parasympathetic activation; this may be the product of reflex conditioning. Modest lowering of blood sugar levels can also act in synergy with hypotension and hypocapnea to induce loss of consciousness. Psychogenic syncope may be mediated through a mechanism involving hypoglycemia. Reflex conditioning perhaps accounts for the small but consistent fraction of the adult population who have repeated fainting episodes. PMID- 1437056 TI - Recurrence of a solitary bone cyst of the mandibular condyle in a bone graft. A case report. AB - The recurrence of a solitary bone cyst of the mandibular condyle in a costochondral bone graft is reported. A solitary bone cyst of the right condylar head and neck of a 10-year-old boy was treated by total resection and immediate reconstruction with a costochondral bone graft. Two years after the first operation, a recurrence of the solitary bone cyst within the bone graft was noted. An open treatment was performed. A review of the literature on solitary bone cysts and recurrences of solitary bone cysts shows that the case reported is unique. Possible reasons for the recurrence are discussed. PMID- 1437057 TI - Diffuse sclerosing osteomyelitis (chronic tendoperiostitis) of the mandible. An 11-year follow-up report. AB - Diffuse sclerosing osteomyelitis of the mandible is a disease that is characterized by a protracted course of recurrent pain, swelling of the cheek, and trismus. The cause of the lesion has been obscure for a long period of time. Recent research, however, pointed out that this disease is likely to be caused by overuse of the jaw musculature (chronic tendoperiostitis) and can be treated accordingly. The protracted course of the disease and the difficulty of treatment with an eventual positive outcome are illustrated by a case report of a 65-year old man with an 11-year history of diffuse sclerosing osteomyelitis (chronic tendoperiostitis) of the mandible. PMID- 1437058 TI - Bronchogenic metastasis to the gingiva. AB - We report a rare case of a bronchogenic adenocarcinoma metastatic to the lower gingiva as the first clinical sign of metastatic disease. The following safe approach is recommended: a tumor in the oral cavity should be regarded as malignant or as a metastasis until the hypothesis can be abandoned. PMID- 1437059 TI - Comparative trial of oral clotrimazole and nystatin for oropharyngeal candidiasis prophylaxis in orthotopic liver transplant patients. AB - A prospective randomized study was conducted to assess the effectiveness of clotrimazole troches and nystatin suspension to prevent oral candidiasis in immunosuppressed orthotopic liver transplant patients. Thirty-four patients received either clotrimazole troches, 10 mg, five times daily, or nystatin suspension, 500,000 units, four times daily. Prophylaxis was initiated after extubation after transplantation and continued throughout the hospitalization. One of 17 patients in each treatment group developed clinical and microscopic evidence of an oropharyngeal Candida infection. This gave an intragroup and an overall infection rate of 5.9%. It appears that either nystatin or clotrimazole may be used for candidiasis prophylaxis in orthotopic liver transplant patients. PMID- 1437060 TI - Clinical evaluation of fifty-six patients referred with symptoms tentatively related to allergic contact stomatitis. AB - During a 7-year period, 56 patients were referred to the Department of General Pathology and Internal Medicine and the Department of Dental Materials, University of Amsterdam, to determine whether contact allergic reactions to dental materials were the cause of their complaints. On the first consultation with the patient a detailed history focusing on the complaints themselves, general medical history, and special clinical history of allergic skin reaction was obtained. Oral examinations were performed, and all patients were referred to the allergy clinic at the department of dermatology for skin tests. There was a strong female predominance in the referred group. Most of the patients with allergic contact stomatitis mentioned a burning sensation in the mouth. In only 16 of the 56 patients could the diagnosis of allergic contact stomatitis be established. From this study it can also be concluded that the combination of a positive allergic history and positive allergic skin reactions with or without visible oral signs are important for the diagnosis of allergic contact stomatitis. PMID- 1437061 TI - Familial ogee roots, tooth mobility, oligodontia, and microdontia. AB - The term ogee is proposed to describe dome or onion-shaped incisor roots as presented in a family study. A case of ogee permanent upper incisor teeth associated with microdontia, oligodontia, and tooth mobility is described. Forty seven members of the proband's family were examined. The dental abnormalities were found to be of an autosomal dominant pattern of inheritance. PMID- 1437062 TI - Necrosis of the tongue in a patient with intestinal infarction. AB - A patient with a rare combination of bilateral lingual necrosis and intestinal infarction, caused by giant cell arteritis, is described and the literature reviewed. PMID- 1437063 TI - Orofacial manifestations of Melkersson-Rosenthal syndrome. A study of 42 patients and review of 220 cases from the literature. AB - We investigated orofacial manifestations in 42 patients with Melkersson-Rosenthal syndrome who were examined at our institution between 1965 and 1990. Patient histories and histologic and clinical findings were reviewed in detail. These data were compared with the oral findings in 220 cases that were reported in the literature between 1965 and 1990. There were 28 females in our study. The age at onset of signs and symptoms varied widely with a mean of 33.8 years. Most frequent initial signs were labial edema, facial swelling, and Bell's palsy. During the course of the disease, 75% of all patients had labial swelling, 50% had facial edema, and 33% had Bell's palsy. Swelling, erythema, or painful erosions that affected the gingiva, buccal mucosa, palate, or tongue were common intraoral symptoms. A comparison with patients reported in the literature revealed a similar frequency of extraoral symptoms but more prevalent intraoral symptoms in our patients. PMID- 1437064 TI - Oral congenital dermoid cyst in the floor of the mouth of a newborn. The significance of gastrointestinal-type epithelium. AB - A case of congenital dermoid cyst in the floor of the mouth in a newborn is presented. The presence of microcyst formation with intestinal-type epithelial lining and mucin histochemistry are discussed. PMID- 1437065 TI - Oral caliber-persistent artery. Unusual presentations of unusual lesions. AB - Two cases of oral caliber-persistent artery are reported. Both cases were different from the five previously reported oral examples of this unusual entity. One case is the first reported instance of a caliber-persistent artery not associated with spontaneous hemorrhage, inflammation, or ulceration. The clinical importance of this entity to the patient and the treating practitioner is stressed. PMID- 1437066 TI - Bacterial microleakage of Cavit, IRM, and TERM. AB - In this in vitro study, a model system was developed and tested to evaluate the sealing ability of temporary restorative materials used in endodontic access preparations. The materials studied, Cavit, IRM, and TERM, were tested on 40 premolars against a known bacterial species, Streptococcus sanguis. The leakage of bacterial cells was checked 4 and 8 days after initial immersion in the culture. Thermocycling was introduced on the fourth day. After 8 days the cement thicknesses were measured after the teeth had been longitudinally sectioned. Before and after thermocycling, IRM was less leakproof than Cavit (p < 0.05) and TERM (p < 0.05). Thermocycling aggravated percolation in the case of IRM, and decreased the tightness of Cavit, whereas TERM remained leakproof. The thicknesses were as follows: Cavit, 3.73 mm; IRM, 3.45 mm; and TERM, 5.49 mm. There was no statistically significant relationship between thickness and tightness. PMID- 1437067 TI - Coronal dye penetration of the apical filling materials after post space preparation. AB - Forty canals of palatal and distal roots of molars were cleaned and shaped with the use of a step-back technique. Thirty canals were obturated, 10 each with lateral, vertical, and thermafil techniques. Five root canals were obturated without a root canal sealer and served as positive controls. Another five root canals were obturated, and their coronal half was sealed with sticky wax and served as negative controls. The apical 5 to 6 mm of the filling materials were exposed to india ink for 48 hours. The depth of dye penetration was measured in all groups and statistically analyzed. The apical plugs in the thermafil group had the highest degree of coronal leakage. The ANOVA test showed a significant statistical difference between coronal dye leakage between this group and those found in canals filled by lateral or vertical condensation techniques. The results indicate that the apical filling materials obtained by lateral or vertical condensation leak less than those obtained by thermafil. PMID- 1437068 TI - Complement activation by lipopolysaccharides purified from gram-negative bacteria isolated from infected root canals. AB - The purpose of the present study was to investigate the complement activation by lipopolysaccharides purified from Porphyromonas (Bacteroides) endodontalis, Veillonella parvula, and Fusobacterium nucleatum isolated from infected root canals. The rate of consumption of the C3T component of the complement increased remarkably when lipopolysaccharides of more than 10 micrograms were added. PMID- 1437069 TI - Direct digital radiography for the detection of periodontal bone lesions. AB - In this study the diagnostic accuracy of D-speed and E-speed film in the detection of simulated periodontal bone lesions was compared with that of an electronic direct digital image receptor. Lesions of increasing depth were created in 11 human hemimandibles at the buccal cortical plate in the interproximal marginal bone area by means of 1.4 mm diameter round bursa. Specimens were imaged at each lesion stage with the use of all three receptors. Nine viewers used a 5-point rating scale to evaluate whether lesions were present or absent in the resulting images. Receiver operating characteristic curves were generated, and maximum-likelihood curve areas were calculated. The area under the curve was used as the index of diagnostic accuracy. The mean receiver operating characteristic areas for D-speed film, E-speed film, and the direct digital system were 0.745 +/- 0.038, 0.740 +/- 0.038, and 0.741 +/- 0.037, respectively. Critical ratio analysis was used to compare the means. No statistical difference was found between any of the three image receptors (p > 0.05) for the detection of simulated periodontal lesions 1.0 to 3.0 mm in depth, which suggested that the digital system performed comparably with conventional film systems. PMID- 1437070 TI - Radiographic demonstration of oronasal fistulas in patients with cleft palate with the use of barium sulfate contrast. AB - The purpose of this investigation was to determine the overlapping and unique contributions that radiographic techniques might provide for accurate characterization of hard palate fistulas associated with cleft palate. Five subjects with oronasal fistulas were selected for radiographic imaging, and their informed consent was obtained. Results indicated that radiographs with contrast can provide important supplemental and unique information. Qualitative descriptions of the inferior-superior course and location, and the size of the narrowest aperture could be obtained from the combination of maxillary occlusal, posteroanterior tomographic, and lateral tomographic projections. This information could not be obtained from the common clinical methods in use to describe fistulas. This technique can provide valuable information to all members of a multidisciplinary cleft palate team to document palatal fistulas for both clinical and research purposes. PMID- 1437071 TI - Winchester syndrome. A case report and literature review. AB - The mucopolysaccharidoses are a group of inherited lysosomal storage diseases that are caused by a deficiency of specific enzymes. The acid mucopolysaccharides are stored in tissue and excreted in large quantities in the urine. The storage of this material leads to effects on a wide variety of tissues and to remarkable changes in morphologic features. Winchester syndrome is a rare disorder in the group of mucopolysaccharidoses. This article is a report of a case with classic clinical, radiologic, and biochemical characteristics of the Winchester syndrome. PMID- 1437072 TI - Root malformation. PMID- 1437073 TI - Contraindications to vasoconstrictors in dentistry: Part I. Cardiovascular diseases. AB - This article reviews the main contraindications of vasoconstrictors in cardiac patients, notably unstable angina, recent myocardial infarction, recent coronary artery bypass surgery, refractory arrhythmias, untreated or uncontrolled hypertension, and untreated or uncontrolled congestive heart failure. Extensive survey of the literature has been completed, giving specific guidelines for a rational use of vasoconstrictors in this category of medically compromised patients. PMID- 1437074 TI - Contraindications to vasoconstrictors in dentistry: Part II. Hyperthyroidism, diabetes, sulfite sensitivity, cortico-dependent asthma, and pheochromocytoma. AB - Dentists are aware of contraindications to the use of vasoconstrictors in patients with cardiovascular diseases. However, there are some other noncardiac conditions we should know. This article discusses the absolute contraindications to the use of vasoconstrictors in patients with a history of hyperthyroidism, diabetes, allergy to sulfites, asthma, and pheochromocytoma. PMID- 1437075 TI - Intraoral vesicles occurring after alginate impressions. AB - In 47 of 227 dental students intraoral vesicles developed after multiple alginate impressions. The lesions were generally solitary and clear, and appeared within 24 to 48 hours after the impression. They were most frequently located inside the vermilion border of the lips and resolved spontaneously in 2 to 5 days. The purpose of this study was to determine the cause of these reactions. Histopathologically one lesion was suggestive of a contact allergy. Cutaneous patch tests, which proved negative, were performed on 14 students to determine whether an allergy to the alginate flavoring existed. The surface of three lesions were cultured and the organisms identified. Contamination studies were carried out on seven unopened containers of the alginate powder and resulted in the isolation of some organisms similar to the mucosal cultures; however, no relationship can be proved. These findings indicate that the cause of the vesicles remains unknown, and further studies are necessary to establish the cause. PMID- 1437076 TI - Appropriate effectiveness: a tale of carts and horses. PMID- 1437077 TI - An initial assessment of the Veterans Affairs occurrence screening program. AB - The Department of Veterans Affairs (VA) established a computerized occurrence screening program in its medical centers in October 1988. Data collected from these hospitals suggest that occurrence screening has been a useful component of the VA's overall quality assurance effort; opportunities for improvement were found in 4.2% of all occurrences. When asked to name the three most effective criteria, there was strong agreement among participating hospitals--50% or more of the facilities ranked readmissions, death, and admission within three days of an unscheduled outpatient visit as the most effective. A majority of facilities (56%) named occurrence screening as one of the more effective elements in identifying quality-of-care issues. These findings must be balanced against important limitations of the occurrence screening process; however, guided by the data it collected, the VA has recently made several changes in its occurrence screening program to address these limitations. PMID- 1437078 TI - Lessons learned from an early attempt to implement CQI principles in a regulatory system. AB - This article describes the Quality Assurance Project (1978-1982), which was developed as a demonstration project by a Wisconsin research team and was intended to implement and evaluate new methods for carrying out the regulatory roles of facility and resident assessment in Wisconsin nursing homes. The new method included (1) a screening process to distribute efforts between sanctioning and process improvement, (2) role changes that would move surveyors beyond problem identification toward education and consultation, and (3) a resident review process based on efforts to find systems-level problems. For the first three years of the project (reported here) certain principles were followed, many of which were similar to those of continuous quality improvement (CQI). Although this is an imperfect example of CQI implementation in a regulatory organization, it contains important lessons that may be helpful in integrating the CQI philosophy into other external review efforts. PMID- 1437079 TI - New methods for evaluating utilization management programs. AB - Blue Cross and Blue Shield of Massachusetts, Inc (BCBS), has developed two new methods for measuring the effect of utilization management (UM) in reducing unnecessary hospital use. The "program component" method measures the separate effect of preadmission review, concurrent review, and discharge planning. The "savable days" method produces a composite measure of the effectiveness of the program as a whole. The use of these two methods is illustrated with five years of utilization review data from the BCBS nongroup insurance product. The results can be used by operations managers and policymakers to measure the performance of individual UM components and the program as a whole, to establish goals and monitor program performance, to modify the program in response to changing utilization patterns, to assist in developing premiums, to establish risk-sharing agreements with employers or providers, and to demonstrate the effectiveness of the program for use in marketing. PMID- 1437080 TI - Strategies for health care reform highlight managed care meeting. PMID- 1437081 TI - Audit for undertransfusion as well as for overuse of blood components. PMID- 1437082 TI - A patient transport pilot quality improvement team. AB - The transportation of inpatients within the hospital is a critical component of the patient care process. A quality improvement (QI) team at Massachusetts General Hospital (Boston) convened to improve this process and to pilot the QI approach there. Pilot QI projects have the burden of intense scrutiny by senior management at a point when the fundamentals needed for a successful QI project are scarce or not yet available. The authors, who were participants in this project, describe the methodology and outcomes of this pilot QI process as well as the lessons learned. The results confirm that, although difficult, it is possible to succeed in pilot projects and gain the support needed to move on to the next step in the QI journey. PMID- 1437083 TI - Review of medical care in cited nursing homes: key areas of deficiency. AB - This article identifies key areas of physician performance in nursing homes (NHs) cited by state regulators. Six faculty members of the University of Maryland Department of Family Medicine reviewed medical care in ten Maryland NHs, which constituted 6.7% of Maryland's Comprehensive-level beds, with a sample of 547 charts and 81 physicians. The reviewers recorded the absence of expected minimum standards of performance in patient care. Nine of the NHs had been cited and one was anticipating an audit by state regulators. Citation by regulators corresponded with inadequate documentation of patient history and physical examinations, especially of neurologic conditions; with inadequate health care maintenance; with mismanagement of laboratory findings such as bacteriuria; and with lack of medical administrative leadership and quality management. These key areas of physician performance should be regularly assessed or systematically changed in all NHs to maintain at least minimum standards of care. PMID- 1437084 TI - Continuous quality improvement of Pap smears in an ambulatory care facility. AB - This article describes how the H. Claude Hudson Comprehensive Health Center (Los Angeles) implemented a continuous quality improvement program to reduce the unacceptably high rate of nonrepresentative Papanicolaou (Pap) smears (those lacking endocervical component). A review of the literature and telephone surveys indicated that the optimal Pap smear technique includes the use of a cervical cytobrush. Several cytobrushes were evaluated and one was chosen to be used facilitywide. Clinicians were given in-services on the proper cervical sampling techniques using the cytobrush. The rate of nonrepresentative Pap smears decreased approximately 12% during a five-month period; this has been attributed to uniform implementation of the cytobrush technique in nonpregnant patients, in service education, and cooperative teamwork. PMID- 1437085 TI - "National Quality of Care Forum" explores feasibility issues in quality management. PMID- 1437086 TI - Integrating total quality management and quality assurance at the University of Michigan Medical Center. AB - Staff members from the University of Michigan Medical Center (UMMC), 1990 winner of the Commitment to Quality Award, describe how they integrated its quality assurance (QA) program into its total quality management (TQM) strategy. The QA program has changed in recent years to establish quality as a central priority, to educate staff in the importance of quality, and to disseminate information more effectively. While these initiatives were underway, UMMC began to embrace TQM as an operating philosophy. Recognizing both the strengths and weaknesses of QA, staff members have worked to apply TQM principles (eg, focus on processes) to QA while using the ongoing monitoring of QA to identify opportunities for improvement within the organization's TQM management system. PMID- 1437087 TI - The financial benefits of an effective hospitalwide quality assurance/utilization management program. AB - This article describes the organizational structure and functions of the quality assurance/utilization management (QA/UM) department at The Johns Hopkins Hospital (Baltimore), which has developed a proactive QA/UM program for identifying opportunities to control inappropriate inpatient admissions, shorten a patient's length of stay, monitor the use of ancillary services, and improve physician documentation in patient medical records. In addition, the QA/UM department has developed and implemented an aggressive third-party appeal mechanism to ensure that the institution has an effective UM program. The QA/UM department annually recovers more than 3 million dollars for the hospital by aggressively appealing third-party payer denials. Specific chart-review variables are outlined. PMID- 1437088 TI - The development of quality assurance in the German health care system. AB - Quality assurance efforts in the German health care system have primarily been a responsibility of the medical profession. The Federal and State Physician Chambers coordinated early quality assurance studies, which conformed to the guidelines of voluntary participation by physicians, confidentiality of data, and no imposition of sanctions for poor performance. These guidelines were challenged by the Health Reform Act of 1989, which made the legal regulations for quality assurance the same for hospitals as for out-patient care. Some current draft implementation plans conform to the principle of anonymity, requiring no disclosure of patient-specific, physician-specific, or hospital-specific data to third parties; others allow release of data to individual insurers or their associations. Although no consensus has been reached as to how quality assurance will be performed in the future in Germany, it will clearly become an integral part of the system. PMID- 1437089 TI - Reforming health care from experience. PMID- 1437090 TI - A transformation in health care decision making. PMID- 1437091 TI - Understanding the dynamics of hospital quality measurement. PMID- 1437092 TI - The physician and employee judgment system: reliability and validity of a hospital quality measurement method. AB - Hospitals engaged in quality improvement must measure and assess customer perceptions of hospital services. Hospital customers are either "external"- patients, their families, and payers--or "internal"--physicians and hospital employees. This article describes two measurement systems designed to gather information from internal customers about the quality of hospital services. One system targets physicians, the other hospital employees. This article describes how these systems were developed and pilot-tested, and how the results were analyzed. Analysis of results showed the systems to be reliable, valid, and representative. The article also addresses limitations of the research (focus on general acute-care hospitals), interesting findings and implications (the correlation between physicians' and employees' ratings of hospital quality), and uses of these measures in corporate-level and hospital-level quality improvement (measuring trends and identifying specific opportunities for improvement). PMID- 1437093 TI - Total quality management in a 300-bed community hospital: the quality improvement process translated to health care. AB - Winter Park Memorial Hospital (Winter Park, Florida) began implementation of a well-strategized plan for total quality management (TQM) in 1987. Having no guidelines for applying TQM to health care but using the industrial quality management techniques of Philip Crosby Associates, Inc, the hospital made the transition and saved thousands of dollars in the process. This article describes the transition, especially the integral part played by the Medical Staff Quality Council in changing the hospital's culture. PMID- 1437094 TI - Integrating external clinical information with the ten-step monitoring and evaluation process: from theory to practice. AB - Traditionally, Sisters of Mercy Health System (SMHS)-St Louis hospitals have had difficulty integrating quality information from external sources into their own monitoring and evaluation activities. This difficulty became apparent at the 14 hospitals of the SMHS when the system headquarters began providing its hospitals with comparative clinical outcome information. Although the hospitals found value in the comparative studies, the information was not fully used in individual hospitals' quality improvement efforts. As a result, SMHS developed a model for integrating external quality information into the local hospitals' ten-step monitoring and evaluation process. This article explains the integration model and shows how it has worked in several clinical scenarios. PMID- 1437095 TI - Health services researchers again focus on policy, management, and clinical practice implications. PMID- 1437096 TI - [Transcranial Doppler sonographic study of the effect of electroconvulsive therapy on the circulation in the median cerebral artery]. AB - The authors monitored the circulation of middle cerebral artery in subdominant hemisphere using the transcranial Doppler sonographic method during electroconvulsive treatment. They intravenously administered the patient 500 mg propanididum to put him/her to sleep and 150 mg of suxamethonium for muscle relaxation. The phasis of narcosis and awakening were continuously recorded under the treatment. After the administration of propanididum a sudden brief rise in flow velocity was measured with transient bradycardia followed by tachycardia. After the muscle relaxation the peak flow velocity diminished long lasting and the mean flow velocity fell from 60 cm per second to 30 cm per second average. At the beginning of the electroconvulsive treatment the velocity suddenly rose. The flow velocity increased significantly during the clonic phase of convulsive jerks with the pulsatility indices falling rapidly. Very low pulsatility indices lasted for long period of time during and following clonic convulsions. PMID- 1437097 TI - [Significance of leukocytes and bacteria in the gastric aspirate from neonates]. AB - The cytological pictures of the gastric aspirates of 2582 newborns were evaluated by a semiquantitative method. A high number of germs was found in the majority of the early onset sepsis and pneumonia (19/22). In the late onset and local connatal infections were found no significant cytological abnormalities. A high number of germs was a rare finding in the healthy newborn population (11/2456). PMID- 1437098 TI - [Duplex ultrasound scanning of the carotid arteries in patients with obliterative diseases of the lower extremities]. AB - The authors practiced carotis duplex scanning examinations on 60 patients having lower limb artery disease. The patients were grouped according to, having cervical bruit or not. In the first group 100% had stenosis while in the second group had only 13.3%. Furthermore the stenosis--plack were analysed according to the severity of the lower limb artery disease. The severity of stenosis can be found in group "A" (bruit exists) and group "B" (no bruit) accordingly to the Fontaine stages. Stenosis higher then 50% was found in group "A" 3 in Fontaine stage II, and 10 in Fontaine stage III. While in group "B" there were no stenosis in Fontaine stage II, and 4 in Fontaine stage III. Out of thet not exceeded 3, 50%, and 1 was subtotal. Likewise, difference can be found of the presence of placks partly in the two groups, partly in the point of view of the stages of Fontaine. There are in group "A" 23 cases with 48 placks, in group "B" 14 cases with 23 placks. Among the patients of group "A" in 10 cases with were in Fontaine II, and 13 in Fontaine III stage. In group "B" 5 were in Fontaine II, and 9 in Fontaine III stage. Authors are calling the attention, that according to their own data, and the sensitivity of duplex scanning this is the most proper examination for recognising the carotid artery sclerosis which is associated with lower limb artery disease. PMID- 1437099 TI - [The use of multivariate mathematical methods in medical diagnostic systems--a model for the evaluation of cytological smears]. AB - The methods of the multivariate mathematics have been applied in several studies to increase the diagnostic reliability of medical decision support system. In the recent years some new algorithms for decision support (fuzzy logic) and for pattern recognition (neural nets), both specified by nonlinearity, were developed. This paper provides results for the application of this methods in the area of quantitative cytology and the comparison with the traditional classifiers. 21 normal, 15 dysplastic, 23 malignant, Feulgen stained gastric imprint smears were analysed on a Leitz Miamed DNA equipment. The determination of mean DNA content, the 2c deviation index (2cDI), 5c Exceeding rate (RcER), G1,S,G2 phase fraction ratios, cell nucleus area, form factor was performed. The discriminant analysis classified correctly the 95.6% of malignant cases, 86.7% of dysplasias, and 80.7% normal cases. Our diagnostic system using fuzzy logic made the diagnostic borders fine tuneable, and reliable. The back propagation neural net could classify all three diagnostic groups above 95% correctly. The application of nonlinear computational methods made the diagnostic system more reliable. The application of these algorithms are encouraged. PMID- 1437100 TI - [Family-centered obstetrics]. AB - Family centralised delivery model program in the Department of Obstetrics of Borsod County Hospital in Miskolc is reviewed. This program has been started since 1986. Significance and positive emotional effects are emphasized. Preparation for the birth, the presence of the husband in the labour ward, the alternative delivery position and the rooming-in system are discussed in detail. The natural birth's behaviour, which is very important in the life of the family, would be realized with this program. PMID- 1437101 TI - [Albert Schweitzer on Hungarian coins]. PMID- 1437102 TI - [Constantine Prphyrogenetos and the medical sciences]. PMID- 1437103 TI - [Cholesterol intake]. PMID- 1437104 TI - [Medical treatment of arteriosclerosis obliterans]. AB - The author gives an overview on former and recent ways of medical therapy in peripheral arterial occlusive disease. The importance of possible elimination of the risk factors is emphasized. The author summarizes the mechanism and clinical effects of drugs affecting vasodynamic as well as thrombolytic processes. The conclusion of the review indicates that although presently there is no ideal therapy for the disease, yet in a remarkable part of cases a marked clinical improvement and inhibition of the basic pathologic processes can be produced even by the available preventive and therapeutical methods. PMID- 1437105 TI - [Bilateral exploration in unilateral inguinal hernia (cost-benefit)]. AB - The authors performed simultaneous inguinal exploration of the right side on 100 girls operated on for the left sided inguinal hernia and hernial sac was found in 73 cases on the right asymptomatic side too. Though the simultaneous bilateral exploration has been proposed by several authors in the case of unilateral inguinal hernia of infants and children, the controversy continues among the pediatric surgeons in this respect at present too. The great number of the hernial sac found on the asymptomatic side according to the authors opinion must be enough to be agreeable with the routine bilateral exploration on girls. There has not been found any publication in the Hungarian literature about this topic. PMID- 1437106 TI - [D-penicillamine: old drug, new indication? D-penicillamine reduced pulmonary hypertension induced by free radicals]. AB - Pulmonary hypertension is one of the major problems in the neonatal period. Free oxygen radicals play important role in the activation of pulmonary vasoconstriction. Since D-penicillamine has proved to be a strong antioxidant in newborns it was of interest to investigate the effect of the drug in the oxygen radical induced pulmonary hypertension. According to our animal experiments D penicillamine inhibits the xanthine oxidase induced pulmonary hypertension in piglets. The same inhibitory effect was observed in the prostanoid metabolism. Could D-penicillamine be used in the treatment of pulmonary hypertension in the newborn? PMID- 1437107 TI - [Spontaneous pneumoperitoneum localized in the left posterior pararenal space in acute pancreatitis]. AB - The authors have analysed the 220 native, erect and supine abdominal X-ray views of 65 males and 45 females with the acute pancreatitis. The localized spontaneous pneumoretroperitoneum inside the left posterior pararenal space was observed in 3.8% of patients (4 cases). The extraperitoneal gas paralleled laterally and inferiorly the margins of kidney and medially the lateral margin of the iliopsoas muscle. Superiorly the gas collection overlay the suprarenal area and outlined the medial crus of the diaphragm, occasionally. The plain-film roentgenogram depended on the quantity of the extraperitoneal gas and of the perirenal fat, besides the subdiaphragmatic adhesions. The pathognostic pneumoretroperitoneum evolved within the initial stage of acute pancreatitis. Afterwards the extraperitoneal gas was hidden by the intraluminal gas bubbles and fluid levels of the dilated small and large bowels. PMID- 1437108 TI - [Increased use of pancreas transplantation in the management of diabetics]. AB - The surgery looking for new ways takes part in the treatment of the type I diabetic patients. The development of pancreatic transplantation in the last decades is discussed. Nowadays the procedure has become accomplished and widely used in the transplantation practice. According to the results of the clinical trials the pancreatic transplantation can normalize the metabolism and improve the quality of life. By improving also the survival of the simultaneously transplanted kidney the procedure has become increasingly indispensable complement of the kidney transplantation in the treatment of type I diabetic patients with end stage kidney disease. PMID- 1437109 TI - [Hospital on Round Hill. (Historical notes on the hospital of the Diosgyor steel mill]. PMID- 1437110 TI - [Public health in Budapest at the turn of the century]. PMID- 1437111 TI - [The intrauterine contraceptive device]. PMID- 1437112 TI - [New trends in the treatment of exocrine pancreas deficiency]. AB - Economic function of the exocrine pancreas is based on non-parallel synthesis, transport and secretion of pancreatic enzymes during basal state and postprandially. Reserve capacity of acinar cells is also augmented by adaptation to the diet as well as by regeneration. In mild pancreatic insufficiency complex dietetic considerations help to maintain the necessary secretory capacity of the pancreas. In severe cases effective substitution therapy is mandatory and increasing lipase survival by dietetic maneuvers, by optimizing trypsin and chymotrypsin levels as well as acid and bile secretion can significantly ameliorate results of replacement therapy of steatorrhea. However, in painful chronic pancreatitis high protease activities seem to be beneficial. Individual replacement therapy with pancreatin preparations adapted to the requirements of the patient has to be chosen in difficult cases. PMID- 1437113 TI - [Acute childhood hemiplegia ]. AB - Stroke in children has been considered to be the most important cause of acute infantile hemiplegia. The author studied 32 patients with childhood stroke. Of the patients 20 had ischemic stroke, and 12 had hemorrhagic stroke. There is an increase of ischemic stroke cases without known predisposing factors in spring. The possibility of nasopharyngeal infection of ischemic stroke in childhood is emphasized. PMID- 1437114 TI - [Significance of phenotypical properties in extra-intestinal E. coli infections]. AB - Virulence factors (serogroup, haemolysis, haemagglutination, antigens K1, K5, colicinogenicity) and their association with diseases of 3334 Escherichia coli strains isolated from different clinical specimens between 1979-1990 were analysed. Strains, that were isolated from cerebrospinal fluid of newborns under one month were characterized by certain serogroups (O7, O18, O45, O78, O83), possession of antigen K1 and production of colicin. On the basis of their LD50 they belonged to the pathogenic group (i.e. < 10 10(6)) significantly more frequently than those isolated from other materials. Strains originating from blood cultures belonged frequently to serogroup O4, O6, O18 and were haemolytic. Their pathogenicity was proved by mouse lung toxicity test. Properties of strains isolated from wound and throat swabs, urinary samples resembled to that of strains originating from blood cultures in many respects, expressing the fact that bacteria settle in different organs before sepsis is developing. Frequent occurrence of strains with antigen K1, haemolysin and haemagglutination positivity in vaginal swabs expose newborns to danger. Knowledge of virulence markers and prevention of infections are associated. PMID- 1437115 TI - [New concepts in the care of the elderly]. PMID- 1437116 TI - [The colours of serotypes]. PMID- 1437117 TI - [Why cavernous tuberculosis was a fatal disease before the invention of tuberculostatic drugs]. PMID- 1437118 TI - [Diagnosis of chronic myeloproliferative diseases]. PMID- 1437119 TI - [Usefulness of exercise test in combination with ECG]. AB - The author gives an overview on usefulness of exercise ECG in cardiology. There is a summary of indications and contraindications of the test and of the personal requirements. The exercise ECG do not recommended to screen asymptomatic individuals. The test is very important in the diagnosis and the prognostic evaluation of patients with ischemic heart disease. The exercise ECG and coronary arteriography are equally important prognostic determinants of future cardiac events. The exercise ECG has been proved an objective tool in the evaluation of functional impairment of patients with congenital and acquired heart disease. The author summarizes the work of exercise laboratories in Hungary, points out the necessity of it's technical improvement and suggests to increase their productivity. PMID- 1437120 TI - [Esophageal dilatation using the Savary-Gilliard sound set]. AB - Authors present a method of esophageal dilatation and report their experiences. The place of esophageal dilatation among other therapeutic approaches of esophageal stricture is discussed. The advantage of Savary-Gilliard bougies and guide wire and its applications are presented. During one and a half year 218 esophageal dilatations were performed at 82 patients. 11 patients were intubated endoscopically. Esophageal perforation occurred in 2 cases (0.93%). Dilatation of the esophagus with Savary-Gilliard bougies and using of the guide wire are considered a safe and many-sided method in the diagnosis and treatment of esophageal strictures. PMID- 1437121 TI - [Otoacoustic emission audiometry in neonates and adults]. AB - The authors discuss the clinical use of the otoacoustic emission audiometry. During the physiological process of sound amplification in the cochlea vibration energy escapes from the inner ear. By the analysis of this sound it is possible to gain information about the function of the cochlea. According to the experiences of the authors the method is extremely useful for screening audiometry in pathological and normal neonates. In adults it can be used for monitoring the cochlear function during ototoxic therapy or noise exposure. PMID- 1437122 TI - [Osteoblastoma in the iliac crest]. AB - An 18 year old male patient is reported with a five year history of mild pain in his right hip. Radiological investigation showed a typical feature for osteoblastoma of iliac bone, with two niduses. En bloc excision was performed. The histological examination's result was also osteoblastoma. PMID- 1437123 TI - [A life in the service of health policy and history of medicine. Gyorgy Gortvay (1892-1966) remembered]. PMID- 1437124 TI - [The role of anatomy in the representation of suffering]. PMID- 1437125 TI - [Labor ending in triple tragedy]. PMID- 1437126 TI - [Dilemma of pediatric surgery. Ethical problems in surgery on neonates]. PMID- 1437127 TI - [Experience with surgical treatment of ascendant varicophlebitis]. AB - In ascendant varicophlebitis, the authors suggest not only crossectomy, but also radical removal of the dilated part of the great saphenous vein and of all thrombosed and non-thrombosed varicose veins in one session. They consider it important to clear the extension of the thrombosis by using an ultrasonic doppler flowmeter or the duplex scan technique; phlebography is needed only if deep venous affection is suspected. Cardinal questions of the operative technique are discussed. In cases of deep venous affection, thrombectomy is performed with Fogarty catheter. Antibiotics are generally held to be unnecessary, but early mobilisation and postoperative low-dose heparin prophylaxis are of great importance. No significant complications were detected after 37 interventions. Every patient was controlled one year after surgery. Residual complaints were found more rarely in the radically treated group. As concerns the quick and definitive recovery, mention is made of favourable economic consequences of the active surgical treatment. PMID- 1437128 TI - [Pseudoaneurysm in a pancreatic pseudocyst]. AB - Four cases with pseudoaneurysm developed on the basis of pancreatic pseudocyst are reported. Regarding data obtained from literature diagnostic and therapeutic possibilities and their success rates are analysed. Authors summarize both specific and non-specific signs of the pancreatic pseudoaneurysm obtained from duplex scan. All of their patients were successfully treated by operation. They call attention to the benefit of the selective feeding artery ligature. Importance of ultrasound follow up of patients suffering from pancreatitis is pointed out, as a prevention of the massive hemorrhage which is the most serious complication of the pancreatic pseudoaneurysm. PMID- 1437129 TI - [Mortality among mature neonates requiring intensive care]. AB - Causes of mortality among term infants hospitalized in a Neonatal Intensive Care Unit during a period of five years were investigated. Among the 107 fatal cases analyzed, congenital malformation was the cause of death in 63 and hypoxia/asphyxia in 35 cases, whereas 9 newborns died primarily of infection. Though congenital malformation is the leading cause of mortality, nevertheless, also perinatal asphyxia and primary and secondary infections play an important role. The utmost importance of prevention and proper medical care is emphasized. PMID- 1437130 TI - [Etiological diagnosis of pneumonia]. PMID- 1437131 TI - [Etiological diagnosis of pneumonia]. PMID- 1437132 TI - [Etiological diagnosis of pneumonia]. PMID- 1437133 TI - [Satisfaction in the work place...]. PMID- 1437134 TI - [Work under different conditions! Interview with Jasmin Hadas, RN, a colleague who came to Austria from Slowenia. Interview by Karl Ertler]. PMID- 1437135 TI - [European Nursing Group and Standing Committee of Nurses of the EC]. PMID- 1437136 TI - [Diabetes consultant]. PMID- 1437137 TI - [Nursing of patients with diabetes]. PMID- 1437138 TI - [My life--thanks to insulin]. PMID- 1437139 TI - [Smoke gets in your eyes...]. PMID- 1437140 TI - [Planned change in nursing legislation]. PMID- 1437141 TI - Identification of complex formation between two intracellular tyrosine kinase substrates: human c-Rel and the p105 precursor of p50 NF-kappa B. AB - Immune complexes of the product of the c-rel protooncogene and of p105, the p50 NF-kappa B precursor, isolated from human T-lymphoblastoid cell lines are comprised of multiple proteins. Only p105 and human c-Rel (hc-Rel) are common to complexes precipitated with antiserum directed against either p105 or hc-Rel. Both proteins are inducible by phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA) and their subcellular distribution is affected by this induction. We demonstrate that the Rel immune complex contains a protein with a molecular weight in the 40 kDa range (p40) which apparently is exclusively cytoplasmic. We were not able to detect p40 in the p105 immune complex, though hc Rel is present. This indicates that hc-Rel exists in different multi-protein complexes and fits a model of functional regulation mediated by differential protein-protein interaction. We also demonstrate considerable isoform diversity of both hc-Rel and p105. We show that this heterogeneity is, in part, the result of phosphorylation. Furthermore, we demonstrate that p105 and hc-Rel are tyrosine kinase substrates. This finding indicates a role for both proteins in intracellular signal transduction pathways which are modulated by modification of their phosphorylation status. PMID- 1437142 TI - Multiple intragenic elements regulate the expression of the murine N-ras gene. AB - We have identified two separate regions within the murine N-ras transcription unit which may participate in the regulation of N-ras gene expression. One of these regions, localized to the first half of intron 1, contains a site of premature transcriptional arrest. We propose that premature transcription termination, which has been identified as an important control mechanism for several genes, may also play a role in the regulation of the N-ras gene. In addition, we have identified a positively acting region within the N-ras transcription unit. This region, localized to the end of intron 1/beginning of exon 1, was found to greatly increase expression from the N-ras promoter. PMID- 1437143 TI - Catalytic properties, tissue and intracellular distribution of neurofibromin. AB - The neurofibromatosis type 1 (NF1) gene encodes a protein, neurofibromin, that shows homology with members of the GTPase-activating protein (GAP) family. To study neurofibromin, rabbit polyclonal antisera were raised against two synthetic peptides. These antisera immunoprecipitated a specific protein of about 240 kDa in lysates of adult murine and rat tissues both in the soluble (S100) and to a lesser degree in the particulate (P100) fractions. The neurofibromin immunoprecipitated from the lysates of several murine organs stimulated the intrinsic GTPase activity of p21 c-Ha-ras protein. Based on immunoblotting, immunoprecipitation and GTPase assays, neurofibromin appears to be at least 10 fold more abundant in the brain than in the other murine organs. The GTPase stimulatory activity of full-length neurofibromin, like the catalytic GAP-related domain, is inhibited by arachidonic acid and the detergent dodecyl maltoside, while phosphatidic acid, containing arachidonic and stearic acid, is non inhibitory. Immunofluorescence analysis with anti-neurofibromin sera in NIH3T3 cells suggests that at least some of the cellular protein associates with cytoplasmic structures that are distinct from actin or tubulin filaments. PMID- 1437144 TI - p53 mutations in Raji cells: characterization and localization relative to other Burkitt's lymphomas. AB - The nuclear phosphoprotein p53 is an important regulator of cell proliferation in normal cells. Interestingly, the gene encoding p53 has usually undergone mutations in a wide range of tumor types. Recent studies of the p53 gene in Burkitt's lymphomas have demonstrated that mutations are extremely common, and in fact it is rare that both alleles of the p53 gene in these tumors are not inactivated by mutation or deletion. We present here genetic data regarding the status of the p53 gene in the Burkitt lymphoma cell line, Raji. As is typical for this type of tumor, both alleles have undergone point mutations. Further, statistical analysis of available data from a large number of Burkitt's lymphomas indicates an apparent tumor-specific distribution of p53 mutations. The possibility that specific mutations of the p53 gene may be important for different tumor types is discussed. PMID- 1437145 TI - Identification of the product of two oncogenic rearranged forms of the RET proto oncogene in papillary thyroid carcinomas. AB - In papillary thyroid carcinomas, we have identified two tumor-specific rearrangements of the RET proto-oncogene leading to the formation of different transforming fusion products sharing the tyrosine kinase (tk) domain of the proto oncogene and designated ptc-1 and ptc-2. We have analysed ptc-1 and ptc-2 products by immunoprecipitation with specific anti-RET antibodies followed by immunoblotting with the same reagent or with antibodies specific for phosphotyrosine (P-tyr) residues. The anti-RET antibodies were reactive with 64 kDa (p64ptc-1) and 81-kDa (p81ptc-2) proteins from lysates of ptc-1 and ptc-2 transformed cells, respectively, and identified two proteins of 140 kDa and 160 kDa from extracts of SK-N-SH, a neuroblastoma cell line previously shown to express two differently glycosylated forms of the normal RET product. The anti P tyr antibodies, while detecting the same p64ptc-1 and p81ptc-2 proteins from ptc 1 and ptc-2 extracts, did not show any specific band in the neuroblastoma lysates. An additional set of experiments led us to conclude that, whereas the normal product of the RET proto-oncogene is a membrane-associated receptor-like molecule not intrinsically phosphorylated on tyrosine, both oncogenic forms of RET, ptc-1 and ptc-2, are constitutively phosphorylated on tyrosine, display an 'in vitro' autophosphorylation activity, are translocated from the membrane to the cytoplasm and are apparently unaffected by protein kinase C modulation. PMID- 1437146 TI - Both myeloproliferative disease and leukemia are induced by transplantation of bone marrow cells expressing v-myc. AB - An in vivo system has been established to investigate v-myc-induced hematopoietic neoplasia in mice. A Moloney murine leukemia virus (Mo-MLV)-derived recombinant retrovirus containing v-myc was used to infect immature bone marrow cells, and these cells were then transplanted into lethally irradiated recipients. All provirus-positive reconstituted mice were found to develop hematopoietic proliferative disorders and, in certain cases, overt leukemia--myeloblastic, myelomonocytic and T lymphocytic. In all cases expression of v-myc was high and the disease type did not correlate with the level of expression. We have isolated immortalized monocytes, myeloid progenitors and T lymphocytes from several of these mice and shown tumorigenicity in secondary syngeneic recipients. This system provides a model for investigating the progression from a pre-leukemic disease to malignancy. In addition, we describe a recombinant v-myc-containing retrovirus that directs high-level v-myc expression from the Mo-MLV promoter in all the hematopoietic cell types examined. PMID- 1437147 TI - PCTAIRE-1 and PCTAIRE-3, two members of a novel cdc2/CDC28-related protein kinase gene family. AB - We have isolated two murine cDNAs designated PCTAIRE-1 and -3 which encode putative serine/threonine-specific protein kinases. The predicted products of PCTAIRE-1 and -3 are 65% homologous and are organized into a core 295-residue kinase domain flanked by unique 161 and 117 amino acid N-terminal and 40 and 39 amino acid C-terminal domains respectively. The kinase domains are approximately 50-55% homologous to members of the cdc2/CDC28 kinase gene family, and each contains a cysteine-for-serine substitution within the conserved PSTAIRE motif. PCTAIRE-1 was ubiquitously expressed as a predominant 3.0-kb transcript and a minor 2.2-kb mRNA resulting from differential polyadenylation. In contrast, PCTAIRE-3 exhibited a more restricted pattern of expression with a single 3.0-kb mRNA detected in brain, kidney and intestine. The PCTAIRE-1 and -3 products produced by in vitro transcription-translation failed to bind to p13suc1 but were precipitated by antibodies directed to Schizosaccharomyces pombe p34cdc2 or to the human PSTAIRE motif. Thus, PCTAIRE-1 and -3 are members of a novel subfamily of cdc2/CDC28-related protein kinases. PMID- 1437148 TI - Activation of the c-Raf protein kinase by protein kinase C phosphorylation. AB - The product of the c-raf-1 proto-oncogene is a cytoplasmic serine/threonine protein kinase that appears to be activated in signal transduction from a variety of cell-surface receptors. The mechanism of c-Raf activation upon stimulation of cell-surface receptors is not clear, but there seem to exist multiple pathways of activation which involve tyrosine and/or serine phosphorylation of the c-Raf protein in vivo. The activated state of Raf is reflected in an increased apparent molecular weight of the Raf protein in sodium dodecyl sulfate-polyacrylamide gels owing to hyperphosphorylation. The tumor promoter 12-O-tetradecanoyl phorbol 13 acetate (TPA) is one of the agents able to induce this hyperphosphorylation of Raf in vivo, suggesting that protein kinase C (PKC) may be involved in the activation of c-Raf in particular situations. Using recombinant baculoviruses expressing PKC and Raf polypeptides, we show here that conventional PKC types (alpha, beta, gamma) but not novel types (delta, zeta, eta) or the unrelated Mos kinase are able to activate c-Raf in a TPA-dependent manner upon coexpression in insect cells. Direct phosphorylation of the Raf protein with PKC in vitro also enhanced the kinase activity of c-Raf, suggesting that c-Raf acts immediately downstream of PKC in a protein kinase cascade which is triggered by TPA and may lead to transcriptional activation of TPA-inducible genes and tumor promotion. PMID- 1437149 TI - AP-1 (Fos-Jun) regulation by IP-1: effect of signal transduction pathways and cell growth. AB - Transcription factor AP-1 is constituted by the various products of the fos and jun proto-oncogene family members, which associate as dimers to bind with variable efficiency to 12-O-tetradecanoyl phorbol 13-acetate (TPA)-responsive promoter elements (TREs). We have recently shown that DNA binding of AP-1 is regulated by an inhibitory protein, IP-1, whose activity is modulated by phosphorylation. Here it is shown that although AP-1 has a very high affinity for its recognition sequence, its binding to the TRE can be quickly inhibited by the addition of IP-1. IP-1 is more active on AP-1 complexes formed during a shorter period of time. IP-1 activity is blocked by stimulation of the protein kinase C (PKC) signal transduction pathway, achieved by treating HeLa cells with phorbol esters or with a diacylglycerol analog. We observed an increase in AP-1-DNA binding after treatment of the cells with either the calcium ionophore A-23187 or dibutyryl cAMP; this could be ascribed to inhibition of IP-1 activity. A decreased IP-1 activity also correlates with the increase in AP-1-DNA binding after stimulating cells with serum. This suggests that IP-1 is an important target of the various signal transduction pathways. No effect on AP-1 and IP-1 was detected in cells transformed by Ki-ras or v-raf; nor could an effect of inhibition of protein synthesis be observed. We also analysed IP-1 regulation upon differentiation of P19 embryonal carcinoma cells by retinoic acid. We conclude that IP-1 regulation has a pivotal role in the final modulation of Fos Jun by signal transduction pathways. PMID- 1437150 TI - Differential induction of c-fos and c-jun proto-oncogenes and AP-1 activity by tumor promoter 12-O-tetradecanoyl phorbol 13-acetate in cells at different stages of tumor promotion in vitro. AB - A two-stage (initiation and promotion) model of chemical transformation of mouse embryonic fibroblasts was used to elucidate the molecular mechanisms of tumor promotion in vitro. C3H10T1/2 cells which had been initiated with a subcarcinogenic dose (0.5 micrograms ml-1) of benzo[a]pyrene (B[a]P) were isolated after 12-O-tetradecanoyl phorbol 13-acetate (TPA) treatment lasting 12, 24 or 36 days. These series of partially promoted cells were designated T-12, T 24 and T-36 cells. T-12 and T-24 cells exhibited higher anchorage-independent growth on soft agar in the presence of TPA than did the initiated or T-36 cells. Cytosolic protein kinase C (PKC) in the resting state was slightly depleted in T 24 and T-36 cells. Proteolytic down-regulation of membrane-bound PKC was enhanced in T-12 cells compared with the initiated cells after 3 h of TPA treatment. Induction of c-fos and c-jun proto-oncogene expression increased two- to threefold in T-12 cells. Moreover, the basal level of c-fos mRNA progressively increased in T-12, T-24 and T-36 cells. As compared with other cell types, T-12 cells had the highest AP-1 DNA-binding activity at both the basal level and at 30 min after TPA treatment. These results indicate that deregulation of the TPA induced cellular responses occurs in the cells at various stages of tumor promotion, and might be associated with transforming processes. PMID- 1437151 TI - Identification and quantification of a carcinogen-induced molecular initiation event in cell transformation. AB - All transformed foci of Balb/c 3T3 clone A31-1-1 cells induced by 7,12 dimethylbenz[a]anthracene (DMBA) (42 out of 42 examined) contained an A to T transversion at codon 61 (A182 to T) of the Ki-ras gene. The transformants induced by other carcinogens tested did not contain such a mutation, except one out of nine 12-O-tetradecanoyl phorbol 13-acetate (TPA)-induced transformed foci. Thus, we hypothesized that this mutation is a specific DMBA-induced initiating event in Balb/c 3T3 cell transformation and we have measured its frequency of induction before transformation occurs, employing our recently developed method. Such mutations can be detected in the cell population as early as 3 days after exposure to DMBA. The same mutation was also detected in the Ha-ras gene. No detectable level (< 10(-6) of these mutations was induced by other carcinogens tested. The mutation frequency of the Ha-ras gene reached a plateau after 1 week's exposure, but that of the Ki-ras gene continued to increase. These results suggest that the A182 to T mutation of the Ki-ras gene, but not that of the Ha ras gene, contributes to morphological transformation of Balb/c 3T3 cells. We have demonstrated that the level of expression of ras genes determines the rate of recruitment of cells into transformation. Quantitative analysis of the frequencies of ras gene mutations (initiation) and of transformation suggests that about 25% of those cells with the Ki-ras mutation were recruited into the full transformation process and that, in the presence of the tumor promoter TPA, about 56% of them completed morphological cell transformation. PMID- 1437152 TI - Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation. AB - Fibroblast growth factor receptor (FGFR-1) is expressed as a single 3.5-kb mRNA transcript in normal human melanocytes and in malignant melanomas as determined upon Northern hybridization to a cDNA clone encoding the membrane-spanning form of the human FGFR-1. Polyclonal antisera directed against the chicken FGFR recognized a 145-kDa protein in primary and metastatic melanomas. Antisense oligodeoxynucleotides targeted against the translation start site and a splice donor-acceptor site of human FGFR-1, in addition to inhibiting the proliferation of normal human melanocytes and malignant melanomas, caused extensive dendrite formation and severe disruption of cell-cell contact--morphological changes that were not observed upon inhibition of the genes encoding basic fibroblast growth factor (bFGF) and retinoic acid-alpha receptor. Thus, unlike in the case of the ligand bFGF, expression of the FGFR-1 may represent a requisite to prevent human melanocytes and malignant melanomas from undergoing (terminal) differentiation. PMID- 1437153 TI - Malignant transformation of human melanocytes: induction of a complete melanoma phenotype and genotype. AB - Human melanoma provides a model to study malignant transformation and tumor progression. Expression of ras oncogenes in cultured normal human diploid melanocytes has induced a subset of phenotypic traits that are characteristic of malignant melanoma cells, including altered morphology, anchorage independence, induction of class II MHC antigens, up-regulation of the ganglioside GD3, and chromosomal abnormalities. However, other characteristics of melanoma, such as loss of expression of adenosine deaminase-binding protein and tumorigenicity, were not observed. We report here that melanocytes infected with a retrovirus containing the viral Ha-ras oncogene underwent complete transformation, acquiring all phenotypic characteristics of malignant melanomas observed in vivo. Transformation occurred in a sequential manner and was associated with spontaneous chromosomal instability. Cytogenetic analysis of transformed melanocytes indicated that the earliest structural chromosomal abnormalities were isochromosomes 6p and 9q followed by complete loss of chromosome 1p, all common karyotypic abnormalities described in human melanomas. The findings suggest that these chromosome regions which are deleted or relatively deficient may contain genes that are critical for the initiation and progression of the melanoma phenotype. PMID- 1437154 TI - Bone marrow-transforming activity of linker insertion mutants of Abelson murine leukemia virus. AB - Two sets of mutants of the Abelson murine leukemia virus, generated by linker insertion mutagenesis of a cloned proviral DNA, were tested for their ability to transform bone marrow cultures in vitro. All the viruses retained an intact tyrosine kinase domain and were competent for transformation of NIH3T3 fibroblasts in culture. One series contained 12-bp linker insertions in the regions flanking the kinase domain, and the other contained frameshift mutations that truncated the gene product downstream of the kinase domain. The majority of the 12-bp insertion mutants retained full bone marrow-transforming activity; only one insertion in the SH2 domain showed reduced activity. This mutant suggests that some aspect of the SH2 domain may be more important in transformation of lymphocytes than fibroblasts. In contrast to the first set of mutants, the bone marrow-transforming activity of the majority of the truncation mutants was significantly reduced or completely lost. We conclude that there is a broad requirement for an intact C-terminal domain of the v-abl protein for the transformation of pre-B cells, but that no single part of this domain is critical. PMID- 1437155 TI - The human tpr gene encodes a protein of 2094 amino acids that has extensive coiled-coil regions and an acidic C-terminal domain. AB - We recently provided evidence that the human tpr gene encodes a 726 amino acid protein (designated tpr-S) and identified an alternatively spliced transcript that encodes a larger tpr protein with an extended C-terminal domain. In this study, through isolation and sequencing of tpr cDNA clones, we have established that this alternatively spliced transcript encodes a protein of 2094 amino acids (designated tpr-L). The larger tpr protein is predicted to have extensive regions of alpha-helix and several stretches of a heptad repeat that is characteristic of proteins adopting a coiled-coil conformation. Furthermore the carboxy domain of this protein is very rich in acidic residues and exhibits homology (58-80%) to the acidic regions of several nuclear proteins, including the Drosophila engrailed protein, Escherichia coli RNA polymerase sigma subunit and nucleolin. To gain additional insight into the function of tpr we examined the expression of tpr transcripts in tissues from adult rat. The highest levels of tpr transcripts were observed in testis, lung, thymus and spleen. PMID- 1437156 TI - elk-1 domains responsible for autonomous DNA binding, SRE:SRF interaction and negative regulation of DNA binding. AB - The ets oncogene superfamily consists of a family of sequence-specific DNA binding transcriptional activator proteins. We have previously identified, cloned and characterized one of the divergent ets-related members elk-1 and shown that it codes for a sequence-specific DNA-binding transcriptional activator. We have also shown that elk-1 forms SRF (Serum Response Factor) dependent ternary complex with SRE (Serum Response Element), similar to p62TCF. In this report, we have mapped the DNA-binding domain of the elk-1 protein (EDB, elk-1 DNA Binding domain) to the 76 amino acid ets homology region. We have also mapped the SRF interaction domain of the elk-1 protein (ESI, elk-1 SRF Interaction domain) to the carboxy-terminal region of the EDB domain. Ternary complex formation by elk-1 requires both EDB and ESI domains of the elk-1 protein. Our results also show that the EDB domain of the elk-1 protein (residues 1-89) binds SRE autonomously, unlike full-length elk-1 protein, suggesting the presence of a potential Negative Regulatory DNA binding domain (NRD) which prevents the binding of elk-1 protein to SRE. Interaction of SRF with the ESI domain allows the elk-1 protein to bind to SRE. Thus elk-1 belongs to a class of transcriptional factors that are involved in gene regulation not only by autonomous DNA binding but also by indirect DNA binding through recruitment by cellular factors. PMID- 1437157 TI - c-fos mRNA constitutive expression by mature human megakaryocytes. AB - By in situ hybridization with a c-fos probe, we have shown that human bone marrow megakaryocytes cultured in the presence of 20% aplastic anemia plasma constitutively express c-fos mRNA. At day 0, megakaryocytes are mostly immature and only 3% of them are labeled. The number of labeled cells reached 23% after 12 days of culture. Interleukin 3 (IL-3) and IL-6 added together at day 10 further increased this number to 31% 2 days later. Mature labeled megakaryocytes were more numerous and more strongly labeled than immature ones. These results suggest that c-fos could play a role in megakaryocytic terminal differentiation, either in the polyploidization or in the thrombopoietic function unique to these cells. PMID- 1437158 TI - Structural organization of a src gene from Xenopus laevis. AB - By sequence analysis of genomic clones, the exon-intron structure of one of the two src genes from Xenopus laevis has been determined. The coding region of the gene is interrupted by 10 introns whose locations are identical to the introns in the coding regions of the src genes of human and chicken. The 5' untranslated region is contained on a separate exon with no sequence conservation relative to the corresponding region of the chicken gene. The 5' untranslated region of the Xenopus gene contains a G + C-rich stem-loop sequence and two ATG triplets. A 1.4 kb fragment containing the 5' untranslated region and sequences upstream of it acts as a promoter when introduced in the correct orientation into X. laevis cell lines. The DNA sequence of this fragment lacks the typical arrangement of TATA and CCAAT sequences but contains the ATGCAAAT octamer sequence and a (TA)39 sequence. PMID- 1437159 TI - In situ dephosphorylation of p53 protein by calf intestinal alkaline phosphatase treatment. AB - The monoclonal antibody (mAb) 1801 has been reported to identify an N-terminal determinant within the tumor-suppressor protein p53 located between amino acids 32 and 79. This region contains two potential sites for serine phosphorylation at amino acids 33 and 46. Using a novel technique which dephosphorylates proteins in situ in fixed permeabilized cells, we have unmasked determinants in p53 recognized by mAb 1801, allowing additional sites of p53 protein to be detected in immunohistochemically reacted cells. This result indicates that phosphorylation at one or both sites within the determinant recognized by mAb 1801 previously blocked antibody-ligand interaction. It further suggests that in situ dephosphorylation may be of more general use in identifying antibodies which can only bind to epitopes in a particular phosphorylation state. PMID- 1437160 TI - A possible role for c-Myc oncoproteins in post-transcriptional regulation of ribosomal RNA. AB - Overexpression of members of the myc family of oncogenes contributes to the development of many vertebrate malignancies. Although several functions for myc gene products have been proposed, the targets for Myc activity during oncogenesis or normal development remain to be identified. Oocytes of Xenopus laevis, which are non-dividing cells that accumulate abundant c-Myc protein, provide an unusual opportunity to examine c-Myc function. We have investigated whether the accumulation of massive amounts of ribosomal RNA (rRNA) by Xenopus laevis oocytes may be related to their elevated expression of myc proto-oncogenes. Our data show that anti-Myc antibodies and some (but not all) c-Myc peptides from conserved regions of the c-Myc protein enhance the turnover of rRNA synthesized in homogenates of oocyte nuclei. These results suggest that one or more members of the Myc protein family may be involved in post-transcriptional regulation of rRNA metabolism. The regulation by c-Myc of rRNA could account, in part, for the generalized stimulation of cells during tumorigenesis. PMID- 1437161 TI - [Tumors of the larynx in Poland in the years 1963-1989]. PMID- 1437162 TI - [Tumors of the larynx in Poland compared to other European countries. Etiologic hypothesis]. PMID- 1437164 TI - [Reinke's edema]. AB - The authors present a theoretical discussion about the histological and anatomical structure of Reinke's space as well as the etiology, clinical features and treatment of Reinke's edema. PMID- 1437163 TI - [Otorhinolaryngologic problems of Wegener's granulomatosis of three months duration]. AB - A case of Wegener's granulomatosis in a 30 years old female was described. The authors have presented the diagnostic difficulties and treatment this rare disease. PMID- 1437165 TI - [Complex method of treating chronic, irreversible peripheral facial palsy particularly considering rehabilitation postoperatively]. AB - Authors described the scheme of the functional reconstruction of the face in patients with protracted, irreversible, peripheral facial palsy and the subsequent rehabilitation. A new, own method of treatment has been introduced considering anatomical and functional relations. PMID- 1437166 TI - [Ultrasonic examination of the larynx]. AB - The aim of our work was the application of sonographic method of the larynx. Aloka Hellige type SSD 280 'LS was used on the examination in real time. Sonographic images of the larynx were obtained in 25 healthy human and 25 healthy children. Sonography may probe to be a potentially useful technique for the examination of the larynx. PMID- 1437167 TI - [Evaluation of surgical techniques used in treating microtia for 35 years]. AB - The author presents an evaluation of the results of surgical treatment in 346 patients with microtia, treated in the previous 35 years, by using different materials to reconstruct the auricle. The reasons for giving-up the application of xenogenic and allogenic cartilage as well as polyester-polypropylene implants to reconstruct the auricular skeleton are explained. A 17-year experience of using autogenic costal-cartilage to reconstruct the auricular skeleton helps to state that early and late complications have been reduced and satisfactory esthetic results have been obtained. To meet their need, the patients were treated for the associated malformations by means of plastic and reconstructive procedures and were referred to other specialists--orthodontic, otologic and prosthetic. PMID- 1437168 TI - [Metastatic tumors of the orbit]. AB - The authors described patients with metastatic tumors, treatment in 1985-1990 year in Otolaryngologist Department Medical Academy in Krakow and dealing with the diagnosis and treatment. It is usually easy treatment the patients with orbital tumors but is very difficult when the orbital tumors are metastatic neoplasms of the orbita. PMID- 1437169 TI - [Stellectomy in the treatment of patients with long QT syndrome]. AB - The authors present the surgical technique of stellate ganglion excision as a therapeutic method in patients with the long QT syndrome. The operations were performed through an anterior supraclavicular approach. Discussing the anatomic considerations, the possibilities of complications and side effects, both temporary and permanent, including Horner's syndrome are reviewed. On the base of the review of present literature and the postoperative results in patients treated in the Otolaryngological Department of the Medical Academy in Bydgoszcz, the authors confirm that the results of stellate ganglion excision in patients with the long QT syndrome are encouraging, but the possibilities of complications, including sudden death after stellectomy, must be taken into consideration. PMID- 1437171 TI - [Fine needle aspiration biopsy in the diagnosis of head and neck tumors]. AB - The results of 3039 fine needle aspiration biopsies of the head and neck tumors were presented. The comparison of cytological and histological examinations in 1141 patients showed that correct cytological diagnosis was established in 84.2% of cases. PMID- 1437170 TI - [Retrospective analysis of mortality due to neoplasms of the larynx in Jelenia Gora district (1982-1989)]. AB - The authors presents a retrospective analysis of mortality from laryngeal cancer in the population of Jelenia Gora in the years 1982-1989. The analysis was based on the death register books and cards. PMID- 1437172 TI - [Determination of oxidative activity of ceruloplasmin using Ravin's method in patients with laryngeal carcinoma]. AB - According to Ravin's method an oxidative activity of ceruloplasmin was determined in the group of patients with carcinoma of the larynx before and after a surgical treatment, in the group of patients with inflammatory lesions in the upper respiratory tract and in the control group of healthy individuals. As a result of this assay the significantly increased of oxidative activity ceruloplasmin was obtained in the individuals with the carcinoma of the larynx (before surgical treatment) in comparison to the group of patients suffering due to inflammatory diseases of the upper respiratory tract and to the group of healthy subjects. Simultaneously a significant decrease of the oxidative activity of serum ceruloplasmin in the individuals with carcinoma of the larynx after a previous surgical treatment was observed. PMID- 1437173 TI - [Evaluation of the ear and vestibular apparatus depending on the anatomy of the cervical spine]. AB - Function of the acoustic organ and the vestibular organ in correlation from radiograph of cervical spinal column was examined in 102 patients aged 20-68 years, of both sexes. The obtained results of audiometric and electronystagmographic investigations have shown that the greatest disorders of function of the acoustic organ and the vestibular organ was at the patients with osteophytes and discopathy in cervical spinal column. Impaired hearing and vestibular disorders was observed also at the patients with normal radiograph of cervical spinal column. The authors have thought that the above deviations can be caused by irritation even the discreet degeneration of cervical spinal column, which ones conduct to increased tension of sympathetic system. PMID- 1437174 TI - Komputerwa analiza, identyfikacja i graficzna prezentacja badan ABR--system audiometrii klinicznej. [Computer analysis, identification and graphic representation of ABR research--clinical audiometric system]. AB - A microcomputer-based system for auditory evoked potentials and tonal audiometry. The software which directs stimulus generation, data recording, displaying and analysis is written in Pascal 5.5. The system hardware is commercially available and of own components. PMID- 1437175 TI - Wplyw rodzaju bodzca dzwiekowego na oznaczanie progu slichowego metoda ABR. [The effect of brief tone envelopes on ABR and behavioral thresholds]. AB - The present study examines the effect of brief tone envelopes on ABR and behavioral thresholds in small groups of normal and hearing-impaired subjects. The hearing-impaired subjects had very steep high-frequency hearing loss in 2-6 kHz region. The stimuli for both ABR and behavioural estimates were 2 and 4 kHz tone burst with linear and nonlinear envelopes. Behavioural thresholds were estimated using a computer controlled, modified block up-down method. The ABR thresholds were evaluated from the recordings collected in automatic acquisition process. Results of our experiments showed that for different stimulus envelopes both behavioural and ABR thresholds were similar in normal range of hearing. However, for impaired ears at high frequencies, both psychoacoustic and ABR thresholds differ, sometimes quite significantly, depending on stimulus envelope. PMID- 1437176 TI - Badania wywolanej otoemisji akustycznej. [Tuning properties of the evoked otoacoustic emission]. AB - The authors present the investigation of evoked otoacoustic emission (EOAE) as a part of the studies of the inner ear function. The EOAE was obtained in 10 normal hearing subjects during the routine recording conditions. In the investigation was used the adjustment of masking tone to obtain a reduction in the (EOAE) most stable component amplitude and suppression of the (EOAE) frequency components (FFT--derived). PMID- 1437177 TI - [Mucociliary transport in the upper airways]. AB - The current views of the ciliary function of the respiratory epithelium are presented. Mucociliary transport in the nose, maxillary atrium, frontal sinus, middle ear and the eustachian tube are discussed. PMID- 1437178 TI - [A case of csf collection under the skin of the cheek]. PMID- 1437179 TI - [Investigations of causes and consequences of head and neck injuries due to circular saws]. PMID- 1437180 TI - [Obituary notice of Prof. Dr. Hab. Med. Hannie Brzezinska]. PMID- 1437181 TI - Kanamycin inhibits cochlear-renal ODC in neonatal rats. AB - Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is important in development and regeneration. We hypothesize that aminoglycoside inhibition of ODC mediates developmental hypersensitivity to aminoglycoside ototoxicity. Kanamycin effects on ODC activity (decarboxylation of ornithine) in vitro were determined in the postmitochondrial fraction of cochlear and renal homogenates from 11-day-old rats. Kanamycin inhibited cochlear and renal ODC by an uncompetitive mechanism. For the cochlear enzyme, the inhibitor constant (Ki) for kanamycin was 99 +/- 25 mumol/L; for the renal enzyme, the Ki = 1.5 +/- 0.1 mmol/L. In vivo effects of kanamycin on cochlear, renal, brain ODC activity were determined in rats treated with kanamycin (400 mg/kg/day, intramuscularly) or saline during postnatal days 11 through 20, the hypersensitive period for ototoxicity. Rats were killed on postnatal days 12, 14, 16, and 20 and ODC was assayed. Kanamycin significantly inhibited ODC in the lateral wall-organ of Corti and kidney (ANOVA alpha = 0.05), but had no effect on cochlear nerve and no consistent inhibitory effect in the brain. These results suggest that ODC is a potential target of kanamycin in susceptible tissues and may be a contributing factor in developmental sensitivity to the drug by inhibiting repair and developmental processes mediated by ODC. PMID- 1437182 TI - Pseudomonas otitis media after eustachian tube obstruction. AB - Previous experiments have shown that Pseudomonas aeruginosa may infect the middle ears of chinchillas by way of the eustachian tube and that chinchillas with acute otitis media (AOM) are more susceptible to pseudomonas infection than animals without AOM. The purpose of this experiment was to examine the effects of otitis media with effusion (OME), induced by means of eustachian tube obstruction, on middle ear susceptibility to nasal inoculation of P. aeruginosa. Chinchilla eustachian tubes were obstructed with silicone rubber sponge bilaterally; OME developed in eight animals (11 ears)--three bilaterally and five unilaterally- and persisted for 6 months. Ten chinchillas with normal eustachian tube function served as controls. All animals were nasally inoculated with 5 x 10(6) colony forming units of P. aeruginosa. Pseudomonas otitis media developed in eight of 11 OME ears with effusion, none of five ears without OME, and four of 20 control ears (chi 2 = 11.782, p = 0.003). Therefore, P. aeruginosa can infect the middle ear by way of the eustachian tube. Tubal dysfunction may lead to the development of chronic suppurative otitis media by increasing tubotympanic susceptibility to opportunistic pathogens. PMID- 1437183 TI - Effect of asymmetric vocal fold stiffness on traveling wave velocity in the canine larynx. AB - The vocal fold (VF) traveling wave is essential to normal voice production. The present investigation describes a new method to determine traveling wave velocity (TWV) in the in vivo canine phonatory model. This method synchronizes photoglottographic and electroglottographic waveforms with videostroboscopic images to determine the duration of time the traveling wave moves between two tattoos placed a known distance apart between the upper and lower margins of each VF. Using this method, we compared the TWV of a paralyzed VF with the TWV of the contralateral, electrically stimulated VF during phonation in two canines. In addition, the presumed VF stiffness asymmetry in the simulated acute recurrent laryngeal nerve paralysis state was confirmed by measuring Young's modulus of each VF. The results indicated that the TWV of the paralyzed VF averaged 55% of the TWV of the normal, stiffer VF when the glottal gap was small and entrainment occurred. This study demonstrated the feasibility of quantifying traveling wave motion in asymmetric VF stiffness disorders. The potential use of TWV in human beings as a target to optimize the phonosurgical results in asymmetric VF stiffness disorders is discussed. PMID- 1437184 TI - Is human galvanically induced triceps surae electromyogram a vestibulospinal reflex response? AB - Interest in understanding the human vestibulospinal reflex has increased enormously over the past three decades, because this reflex is the primary effector of maintenance of posture and balance. On a posture platform, forces exerted by the triceps surae (TS) and tibialis anterior muscles are measured to calculate center of mass sway. We wished to determine whether the TS response is a direct component of the vestibulospinal reflex. Ten healthy human beings were stimulated with sinusoidal galvanic currents delivered over their mastoid processes. Sway response on a posture platform and TS electromyogram (EMG) were recorded for the following conditions: (1) standing unrestrained; (2) standing completely restrained above the leg; and (3) sitting unrestrained. Results were similar for all subjects. Computer-aided analysis for case 1 reveals that TS EMG and horizontal body sway responses are generated at the same frequency as the stimulating current, with a phase lag of 90 degrees. For case 2, body sway response and any component of the TS EMG over the unstimulated condition were absent in all subjects. For case 3, body sway persisted, but no TS EMG above the unstimulated condition was recorded. As the TS EMG disappears when the standing subject is restrained from swaying or in the unrestrained seated subject, we conclude that the TS EMG response is compensatory to motion of more superior portions of the musculoskeletal system; it is not part of the vestibulospinal reflex. PMID- 1437185 TI - Early mucosal changes in experimental sinusitis. AB - Normal mucociliary flow is a significant defense mechanism in the prevention of acute sinusitis. We have undertaken a study to examine the early sinus mucosal and mucociliary changes that occur in response to acute infection. Twenty rabbits were evaluated for 5 days after an obstructed maxillary sinus was inoculated with either Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas aeruginosa, or a sterile saline solution. Data collected included measurements of sinus mucosal ciliary beat frequency, quantitation of ciliated cell losses, and electron microscopic observations. Results demonstrate statistically significant (p < 0.05) changes in mucosal ciliary beat frequency that were either excitatory or inhibitory, depending both on the length of the infection and the specific organism. No changes in ciliary beat frequency were observed in the control animals (p > 0.55). Control animals likewise demonstrated no loss of ciliated cells from mucosal epithelium; however, dramatic losses of ciliated cells from the sinus mucosa of the experimental groups were observed. These losses occurred at different rates, depending on the infecting organism, but all infected groups demonstrated a > 86% decrease in the number of viable ciliated cells from the sinus mucosa after sinusitis of 5 days duration. We conclude that a significant loss of ciliated cells from sinus mucosa and a corresponding disruption of normal mucociliary flow occurs early after exposure to pathogenic organisms and is a significant predisposing factor in the development of acute sinusitis. PMID- 1437186 TI - Preconditioning: a new technique for improved muscle flap survival. AB - Musculocutaneous regional and distal flaps have become an important tool available to the head and neck surgeon. Vascularized autogenous muscle transplants allow single-stage reconstruction of complex defects. Ischemic muscle necrosis is a well-recognized complication with serious potential morbidity. It has been shown that myocardial muscle is protected from ischemic damage by brief periods of coronary artery occlusion and reperfusion subsequent to prolonged ischemia. This is called preconditioning. To our knowledge, this technique has never been extrapolated to skeletal muscle. This article presents a discussion of preconditioning and the potential benefits of this new technique as a means to enhance skeletal muscle survival to sustained normothermic global ischemia. Theories behind ischemic muscle injury are presented. A review of the development of preconditioning in myocardial muscle is discussed. Experimental models used to investigate this phenomenon are also presented. In addition, results of our laboratory investigations using the latissimus dorsi porcine model are discussed. Preconditioning is a new, nonpharmacologic means to improve muscle flap survival. This simple technique may have great clinical application in reducing ischemic muscle necrosis in regional and distal muscle transplantation. PMID- 1437187 TI - Acoustic characteristics of post-thyroplasty patients. AB - This study investigated changes in voice quality after thyroplasty type I in eight adults with unilateral vocal fold paralysis. A silicone rubber implant was inserted through a window in the thyroid ala and placed between the inner and outer perichondrium to externally medialize the abducted vocal fold. Measures of fundamental frequency (vocal pitch), pitch range, maximum phonation time, s/z ratio, pitch perturbation (vocal jitter), and amplitude perturbation (vocal shimmer) were made 1 to 2 weeks preoperatively and 1 month postoperatively. Postoperative voice quality was characterized by an improved pitch range, phonation time, s/z ratio, and pitch and amplitude perturbation. No change was noted in fundamental frequency. Changes in postoperative voice quality were unrelated to the subjects' preoperative age, sex, etiology, and duration of the paralysis. PMID- 1437188 TI - Complications of lumbar spinal fluid drainage. AB - Cerebrospinal fluid fistula is an unfortunate, yet well-recognized, complication of basilar skull fracture, skull base surgery, and neurotologic procedures. Treatment commonly involves the use of continuous lumbar drainage. A retrospective chart review of 32 consecutive patients who required placement of lumbar drain by the otorhinolaryngology and neurosurgical services from March 1988 through July 1991 was undertaken to assess possible complications. The complications found were readily separated into minor and major categories on the basis of the possibility of permanent morbidity or mortality. Minor complications, including subjective complaints of headache, nausea, vomiting, etc., were noted in 59% of patients. Major complications were observed in four of 32 patients (12.5%), including unilateral occlusion of the posterior cerebral artery and unilateral true vocal cord paralysis. Alleviation of all complications was achieved by cessation of lumbar drainage. These cases are presented with discussion of pathogenesis. These findings demonstrate the possibility of potentially serious complications that mandate close monitoring of patients who require continuous lumbar drainage. PMID- 1437189 TI - Head-upright tilt-table testing: a useful tool in the evaluation and management of recurrent vertigo of unknown origin associated with near-syncope or syncope. AB - Recurrent idiopathic vertigo associated with near-syncope and syncope is a common perplexing problem, some cases of which are considered autonomically mediated (vasovagal). Upright-tilt-table testing has emerged as a potential method to test for vasovagal episodes. This study evaluated the use of this technique in the evaluation and management of patients with recurrent idiopathic vertigo associated with near-syncope or syncope. Twenty-one patients with recurrent unexplained vertigo and syncope/near-syncope and 11 control subjects were evaluated by use of an upright-tilt-table test for 30 minutes, with or without a graded isoproterenol infusion (1 to 4 micrograms/min given intravenously), in an attempt to provoke hypotension, bradycardia, or both, which reproduced the patient's symptoms. The patients included 10 men and 11 women (mean age, 51 +/- 16 years). Eleven controls with no history of vertigo were also studied. Transcranial Doppler sonography was used to assess cerebral arteriolar blood flow during tilt. All tilt-positive patients were placed on therapy with either beta blockers, disopyramide, or transdermal scopolamine, the effectiveness of which was determined with another tilt-table study. Symptoms occurred in seven patients (33%) during the baseline tilt and in eight patients (38%) during isoproterenol infusion (total positives, 71%). Transcranial Doppler sonography demonstrated a 225% +/- 192% increase in pulsatility index and a 70% +/- 29% increase in resistance index (indicative of cerebral arteriolar vasoconstriction) at the time of vertigo. No control subject experienced syncope during this test. Each tilt positive patient eventually became tilt-negative with therapy, and over a mean follow-up period of 26 months, no further episodes have occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437191 TI - Distal tracheal stenosis in neonates and infants. PMID- 1437190 TI - Risk factors of cancer of the larynx: results of the Heidelberg case-control study. AB - Squamous cell carcinoma of the larynx is a multifactorial disease. It is firmly linked to several environmental risk factors. In the meanwhile, a considerable amount of epidemiologic evidence has been built up to implicate chronic consumption of alcohol and tobacco, occupation, diet, and social status in the etiology of the laryngeal cancer. Herein is a report from the first case-control study on the role of these risk factors conducted in a German population of patients with laryngeal cancer. PMID- 1437192 TI - Riedel's thyroiditis: report of a lethal case and review of the literature. PMID- 1437193 TI - Odontogenic cervical necrotizing fasciitis with intrathoracic extension. PMID- 1437194 TI - Evaluation of a new ceramic endotracheal tube for laser airway surgery. PMID- 1437195 TI - The laryngeal mask: a new type of airway in anesthesia for direct laryngoscopy. PMID- 1437196 TI - Endoscopic identification of the maxillary sinus osteum. PMID- 1437197 TI - Herniation of temporomandibular joint contents into the external ear canal. PMID- 1437198 TI - The myth of spontaneous perilymph fistula. PMID- 1437199 TI - Comparison of electroglottographic and acoustic analysis of pitch perturbation. AB - Pitch perturbation is a measure of the cycle-to-cycle variation in vocal fold vibration. Perturbation can be assessed by means of electroglottographic or acoustic signals. The purpose of this study was to determine if these two analysis techniques are equivalent measures. The Laryngograph, an electroglottograph, and the Visi-Pitch, an acoustic analyzer, were used to measure pitch perturbation in 80 dysphonic subjects. Both instruments use Koike's formula to calculate relative average perturbation. While intra-subject variability appeared erratic, statistical analysis of intersubject data indicated that the two instruments provided an equivalent measure of pitch perturbation. PMID- 1437200 TI - Nasal reconstruction using split calvarial grafts. AB - The reconstruction of nasal deformities after trauma or surgical procedures presents an arduous task for the reconstructive surgeon. The anatomic alteration of supporting cartilage and nasal bones, as well as scar formation, compound the difficult nature of this type of reconstruction. In the past, multiple autogenous and alloplastic implants have been used in nasal reconstruction. Autogenous implants include auricular and septal cartilage as well as rib and iliac crest bone grafts. Alloplastic materials include acrylic, supramid mesh, Gortex, and silicone rubber. Autogenous grafts have been shown to provide excellent long-term reliable results in nasal reconstruction. In our study, autogenous split calvarial bone grafts were used in the nasal reconstruction of 17 patients. Among the corrective procedures were dorsal augmentation for saddle-nose deformities, insertion of columella struts for nasal tip ptosis, and insertion of nasal battens for nasal valve collapse. Patient followup has been from 1 to 5 years, with no significant resorption noted during that time. Complications were limited to one seroma at the donor site before wound drains were routinely used. No major complications, including hematoma formation, CSF leak, or infection, have been observed. PMID- 1437201 TI - Vestibular rehabilitation reduces functional disability. AB - Vertigo caused by vestibular disorder may be successfully treated with a physical therapy program of graded exercises to habituate the patient to the vertiginous stimulus and to increase the range of motion through which the patient can tolerate moving. Performance on daily self-care tasks is an important indicator of the patient's tolerance for head movement and the success of treatment. In this study, self-care skill in subjects with labyrinthine and brainstem lesions before and after receiving vestibular rehabilitation was examined. Subjects improved significantly after physical therapy, demonstrating greater independence in their abilities to care for themselves. These data provide further support for the value of vestibular rehabilitation procedures. PMID- 1437202 TI - Tympanosclerosis of the stapes: hearing results for various surgical treatments. AB - When tympanosclerosis involves the tympanic membrane or the lateral ossicles, treatment is usually straightforward and uncomplicated. When the stapes is involved, therapy is more controversial and may be more difficult. We report our results in 154 patients who underwent different surgical procedures for tympanosclerosis of the stapes. Followup was up to 10 years. Pure-tone average threshold was significantly improved (p < 0.05) in patients who underwent mobilization procedures or stapedectomy for definitive treatment. The air-bone gap was less than 20 dB at 6 months postoperative in 72% of patients and less than 30 dB in 90%. At 6 months, 2 years, and 5 years there were no statistically significant differences in hearing results between stapedectomy and mobilization patients, some of whom were followed for up to 10 years. No patient had a profound hearing loss after surgery. Surgical treatment for tympanosclerosis of the stapes is a safe procedure, with hearing results similar to those of surgery for other chronic ear diseases involving the ossicular chain. PMID- 1437203 TI - A multisensor solid-state pressure manometer to identify the level of collapse in obstructive sleep apnea. AB - The cause of failure after uvulopalatopharyngoplasty (UPPP) in idiopathic obstructive sleep apnea (OSA) is poorly understood, but has been speculated to be due, in part, to persistent collapse in the lower oropharynx. In order to determine the specific level of upper airway obstruction during sleep, a multisensor pressure catheter has been developed with five solid-state ultraminiature sensors. Four sensors in the pharynx simultaneously measure multiple pressure levels, with no need to move the catheter during sleep. One distal esophageal port measures the respiratory effort. To evaluate the use of this catheter, manometry in twelve patients was reviewed and compared the use of this catheter, manometry in twelve patients was reviewed and compared to simultaneous videoendoscopy. The initial site of obstruction was the palate in nine patients (75%) and the tongue base in three (25%). Three patients with initial obstruction at the palate manometrically demonstrated distal obstruction on subsequent occluded breaths. Furthermore, simultaneous videoendoscopy in four patients with a palatal level of obstruction also identified marked near-total visual collapse without obstruction of the lower oropharynx that was not identified by pharyngeal manometry. The endoscopy revealed that at the initial site of obstruction, collapse appeared to have occurred passively during expiration and not on inspiration. Inferior to the site of manometric obstruction, collapse occurred during inspiration associated with increased negative inspiratory pressures. These results demonstrate that a multisensor pressure catheter can objectively identify the level of obstruction during sleep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437204 TI - Bilateral thyroarytenoid denervation: a new treatment for laryngeal hyperadduction disorders studied in the canine. AB - Adductor spasmodic dysphonia is a vocal disorder of uncertain etiology with no satisfactory long-term treatment. Recently, injection of botulinum toxin (Botax) into the thyroarytenoid (TA) muscle has been used as an effective temporary treatment. A surgical counterpart to bilateral TA Botox injection is described in this article. Bilateral thyroarytenoid denervation was performed through a window in the thyroid cartilage in seven canines, including four that were studied 3 months after the procedure. No serious complications occurred in the animals, each maintaining full vocal fold abduction and adduction. In all cases, anticipated physiologic changes in laryngeal function were observed, including the inability to generate high subglottic pressures during high levels of laryngeal nerve (RLN) stimulation. In two of the surviving animals, the ansa cervicalis was used to reinnervate the TA muscle, thereby preventing the possibility of reinnervation from the proximal RLN stump while limiting TA atrophy and fibrosis. Bilateral TA denervation represents a hopeful new long-term approach to spasmodic dysphonia treatment. PMID- 1437205 TI - Repair of chronic tympanic membrane perforations using epidermal growth factor. AB - Perforation of the tympanic membrane (TM) is a frequent cause of conductive hearing loss. Persistent TM perforations often require surgical repair with an autologous tissue graft to restore hearing and prevent recurrent infection. While highly efficacious, this method of closure requires a relatively complex and expensive microsurgical procedure. We have recently developed a chronic TM perforation model in the chinchilla for use in the exploration of novel methods of TM repair. PMID- 1437206 TI - An evaluation of laryngeal muscle activation in patients with voice tremor. AB - Eight patients with voice tremor were studied to characterize laryngeal muscle involvement. Electromyographic (EMG) recordings were made from intrinsic laryngeal muscles, simultaneously with some extrinsic laryngeal muscles, respiratory movement, and voice recordings during respiration, whisper, and phonation. Spectral measures were used to determine the tremor frequency and the prominence of spectral peaks in the EMG, respiratory and acoustic signals, while correlation coefficients were computed between pairs of tremulous EMG signals to measure the synchrony of tremor between muscles. The intrinsic laryngeal muscles were tremulous during respiration and speech, with the thyroarytenoid most often involved. Tremor was also detected in some of the extrinsic muscle recordings and the percentage of muscles with tremor was higher during phonation than during whisper or respiration. Time delays were found between tremor oscillations in laryngeal muscles. Because the thyroarytenoid was affected in all the patients studied, botulinum toxin injections may be beneficial in treatment of this voice disorder. PMID- 1437207 TI - Incidence of otitis media in vitamin A-deficient guinea pigs. AB - After observing an association between vitamin A deficiency and otitis media among children in Micronesia, we sought to develop an animal model for vitamin A deficiency-induced otitis media. Thirty juvenile guinea pigs were screened for absence for otitis and then divided into two groups. The experimental group was placed on a vitamin A-free diet, whereas control animals were fed a standard formula. The animals were followed by means of otologic examination and serum retinol determinations. When experimental animals demonstrated vitamin A deficiency, they were killed along with one control and temporal bones were harvested and prepared for histologic examination. None of the 15 controls demonstrated middle ear abnormalities. In the experimental group, 77% of temporal bones showed middle ear pathology consisting of either of subepithelial edema (27%) or frank otitis media (50%). These results indicate that the guinea pig is a suitable species for study of otitis media in association with vitamin A deficiency. We postulate that eustachian tube dysfunction is the primary mechanism for inducing middle ear inflammation in this animal model. PMID- 1437208 TI - Pemphigus vulgaris. PMID- 1437209 TI - Natural history of mammalian spermatozoa in the female reproductive tract. PMID- 1437211 TI - The gonadotrophin receptors: insights from the cloning of their cDNAs. AB - The cloning and expression of the cDNA's for the gonadotrophin hormone receptors has confirmed that these receptors are each composed of a single polypeptide which can both bind hormone and activate adenylyl cyclase when occupied with agonist. Although some studies by others have suggested that the LH/CG receptor and the FSH receptor are composed of multiple subunits (Ascoli and Segaloff 1989; Reichert and Dattatreyamurty 1989; Shin and Ji 1985a, b, and c; Smith et al. 1985; Smith et al. 1986), biochemical studies on the LH/CG receptor have shown that it is composed of a single polypeptide with a molecular weight of 93,000 when analyzed on sodium dodecyl sulfate gels in the presence or absence of disulfide reducing agents (Ascoli and Segaloff 1989). As the LH/CG receptor has been shown to be readily proteolyzed into smaller-sized fragments (Ascoli and Segaloff 1986; Ascoli and Segaloff 1989), it is reasonable to postulate that the FSH receptor may be similarly susceptible to proteolysis, and that this may account for the discrepant reports on its structure. Clearly, the molecular cloning and functional expression of the cDNA's for the rat ovarian LH/CG receptor (McFarland et al. 1989) and the rat testicular receptor (Sprengel et al. 1990) demonstrate conclusively that the gonadotrophin receptors are indeed single polypeptides. As shown schematically in Fig. 5.12, the gonadotrophin hormone receptors (together with the thyrotrophin receptor, see Frazier et al. 1990; Libert et al. 1989; Nagayami et al. 1989; Parmentier et al. 1989) define a unique subclass of G protein-coupled receptors. Thus, in addition to the seven membrane spanning domains which appear to be the hallmark of G protein-coupled receptors, the gonadotrophin receptors (and thyrotrophin receptor) also contain large extracellular domains. These extracellular domains are composed of a repeating leucine-rich motif which is found in a number of widely-diverse proteins, collectively termed leucine-rich glycoproteins. We have shown that the extracellular domain of the LH/CG receptor is entirely responsible for binding hormone with high affinity. This is in contrast to the rhodopsin-like G protein coupled receptors which have relatively small amino-terminal extracellular domains and in which the ligands interact directly with amino acids within the transmembrane helices. As with other G protein-coupled receptors, however, it is thought that the gonadotrophin receptors interact with and activate Gs through residues located within the cytoplasmic loops and the amino-terminal region of the cytoplasmic tail.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1437210 TI - Vaccination against pregnancy. PMID- 1437212 TI - Differentiation processes of granulosa cells. PMID- 1437213 TI - Olfaction and reproduction in ungulates. PMID- 1437214 TI - Behavioural endocrinology and reproduction: an evolutionary perspective. AB - It is a fact that those interested in immediate causation tend to be unaware of the great advances in evolutionary biology. Similarly, most scientists interested in ecological and evolutionary questions ignore advances in neurobiology and molecular biology. Quite simply, 'reductionists see little to be gained from holistic studies, and whole organism biologists do not recognize the value of molecular analysis' (Prosser 1986). This philosophical gap and lack of communication between molecular and physiological biologists with organismal and evolutionary biologists makes it difficult to be a generalist. Yet if we are to understand past, present, and perhaps even future behaviour, we must study how the different levels of biological organization are integrated. If done with foresight, it can lead to new discoveries not only in evolution and ecology, but also in physiology and even molecular biology. One of the first things we are impressed by is the great variety of animals, particularly their behaviours and their physiologies. With so many differences, are there any generalities? With the establishment of evolutionary theory, evidence that there is 'unity in diversity' has come with discoveries of common anatomical features, the cell cycle, conservation of intermediary metabolism, and the genetic code, to name but a few. While in vertebrates there appears to be a conservation of the neural circuits underlying sex behaviour, it is still too early to state the extent to which this concept can be extended to the hormonal mechanisms underlying behaviour. This chapter has documented how some widely-held assumptions are generalities only in a very restricted sense. I have tried to show how much of our conceptual understanding of the behavioural endocrinology stems from extensive studies on relatively few species. According to (Beach 1979), there are '... two cardinal rules that should govern not only the construction of animal models for human behaviour, but for all interspecific comparisons regardless of the behaviour and the species involved. The first rule is that meaningful comparisons are based not upon the formal characteristics of behaviour, but upon its causal mechanisms and functional outcomes.... The second rule is that the validity of interspecific generalization cannot exceed the reliability of intraspecific analysis. Significant comparison of a particular type of behaviour in two different species is impossible unless and until the behaviour has been adequately analyzed in each species by itself.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1437215 TI - The chromosome complement of human gametes. AB - The comparisons of observed and predicted rates of chromosomally abnormal gametes for two major classes of abnormality and for three specific trisomies are summarized in Table 2.10. As can be seen there is not very good agreement between the two sets of data. For sperm the observed abnormality rates are, with the exception of polyploidy, all in excess of those predicted. For structural abnormalities the excess is absurd and suggests that most structural abnormalities seen in sperm chromosomes may be preparation artefacts. On the other hand, it could be argued that the excess of hyperhaploidy among sperm is real and represents those trisomic conceptuses lost in the early stages of pregnancy. However, both chromosome 21 and the sex chromosomes are represented more often than any other chromosomes. Recent observations among all clinically recognized pregnancies do not suggest an excess of trisomy 21 conceptions arising from non-disjunction in spermatogenesis. As can be seen from Table 2.10, the observed frequencies of trisomy 21 is 10 times greater than that predicted, a difference that seems too great to be accounted for by early pregnancy wastage. While the X chromosome does appear to undergo non-disjunction much more frequently than the autosomes during spermatogenesis, the increase is restricted to non-disjunction of the XY bivalent at the first male meiotic division. In this class the observed and predicted frequencies are rather similar and it is even possible that the observed excess in sperm is accounted for by early post-zygotic loss. However, with the exception of the 24, XY class, the distribution of individual chromosomes among the hyperhaploid sperm bears little relation to that predicted. The most likely explanation for this is that banding of sperm chromosomes is of such poor quality that there are many errors in the identification of individual chromosomes. Most authors use some form of Q banding and this technique should give unequivocal identification of the highly fluorescent Y chromosome even when other chromosomes are not clearly distinguishable. An increased accuracy of Y-chromosome identification may account for the relative concordance between observed and predicted rates of 24, XY sperm. By the same argument, 24, YY sperm might be expected to be accurately enumerated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1437216 TI - Cooling, cryoprotectants, and the cytoskeleton of the mammalian oocyte. PMID- 1437217 TI - Reader troubled by "refreshing view". PMID- 1437218 TI - DER revises waste management rules. AB - A number of improvements were made in new regulations designed to help physicians manage their infectious and chemotherapeutic wastes more easily. This article summarizes those improvements. PMID- 1437220 TI - HIV procedures opposed by society. PMID- 1437219 TI - Restrictive covenants in physician employment agreements. AB - Virtually all physician employment relationships are governed by employment agreements in which the physician and employer exchange promises. When embodied in contracts, promises are also known as "covenants." Certain covenants are restrictive in nature, including, most notably, covenants which prohibit competition ("non-competes"). Legal considerations regarding non-competes in particular center around the law of restrictive covenants in general. This article identifies legal issues which exist with respect to restrictive covenants under Pennsylvania law and offers certain caveats with respect to the negotiation of the non-competition components of the physician employment agreements. PMID- 1437222 TI - Assessing the impact of RBRVS on revenues. PMID- 1437221 TI - Estate planning: some first steps. AB - After you've worked a lifetime to build an estate, it's possible for the federal government to snatch up to 55 percent of it away from your heirs, and this could happen even if you've made a will. Clearly, an estate not carefully and professionally planned is one destined for lawyers' pockets, the courts, and both federal and state taxes. PMID- 1437223 TI - PRO myths vs. facts. AB - One thing of which the Keystone Peer Review Organization may be rightfully accused is that we are boastful about our efforts to communicate with physicians and providers. We think we do as good a job of education as can be done, and we don't mind saying so. However, certain myths have formed in the minds of some of our fellow physicians which seem impossible to dispel. PMID- 1437224 TI - Is anyone out there? PMID- 1437225 TI - [Scoliosis and spondylolisthesis in children and adolescents]. AB - The genuine structural scoliosis is characterized by a rotation of the vertebral bodies. Clinically suspect cases require an exact radiographic assessment. Treatment is based on the radiographically found COBB-angle: physiotherapy, brace and different types of surgical instrumentation are the most common therapeutic procedures. Early diagnosis is essential for the final therapeutic result! Spondylolisthesis can only be diagnosed by X-ray. Surgical stabilization is necessary if pain, instability or progressive gliding are found. The extent of surgical procedures depends on the stage of the gliding process. Therefore early diagnosis is desirable. PMID- 1437226 TI - [The Nutrition Commission of the Austrian Society of Pediatrics and Adolescent Medicine. Prevention of caries]. AB - Effective preventive programs must be instituted early in the life of a child. The pediatrician plays an important role in preventive oral health care, because most children do not visit a dentist before 3 years of age. Fluoride therapy decreases the caries vulnerability of the tooth, oral hygiene measures are important to remove bacterial plaque, and dietary modifications reduce the number of carbohydrate exposures per day. Community water fluoridation is proposed in Austrian cities, because it continues to be the most cost-effective caries prevention measure available. As long as the population does not have access to optimally fluoridated water, dietary fluoride supplementation offers an effective alternative. The recommended dosage of fluoride supplements for children depends on the amount of fluoride present in their drinking water and on the child's age. Liquid fluoride supplements and chewable tablets are proposed for children between 0.5 and 3 years and children between 3 and 13 years, respectively. Home use topical fluorides and professionally applied topical fluorides are useful beyond 3 years of age. Teaching of oral hygiene measures should be continued in kindergarten and school. The 3-6 year-old children require parental assistance to achieve effective plaque removal. Semiannual dental visits should begin at the age of three and continue throughout childhood and adolescence. As far as the diet is concerned, the frequency of exposure to sugar appears to be the most important factor in the development of dental caries. It now appears that most sugars are nearly equally cariogenic in a pure form. PMID- 1437228 TI - [Transverse fetal position syndrome--a combination of congenital skeletal deformities in the newborn infant]. AB - We describe a pattern of connatal postural deformities observed in approximately 0.6% of otherwise healthy, mature newborn infants. It comprises unilateral flattening of the skull (dolichocephalus), ipsalateral mandibular hypoplasia and torticollis, deviation of the septum nasi, pes calcaneovalgus on one and pes adductus supinatus on the other side. The deformities occur in four distinct combinations attributable to the prenatal lie of the fetus: dorsoanterior or dorsoposterior, left or right oblique lie. The deformities respond well to manipulative therapy. PMID- 1437230 TI - Brugia pahangi infections in immune-compromised rats demonstrate that separate mechanisms control adult worm and microfilarial numbers. AB - The immunological basis of resistance to Brugia pahangi infection in rats was studied. Infections were investigated in athymic rnu/rnu rats and in rats treated with the immuno-suppressive agents cyclosporin A (CsA) or cyclophosphamide (Cy). The recovery of adult worms in normal rats was 1-2% in comparison to 12.2% recovery in athymic rats. CsA and Cy treated rats did not have increased adult worm burdens. Microfilarial (Mf) levels (expressed as Mf per ml per adult worm) were highly elevated in both athymic and Cy treated rats but not in CsA treated rats. IgG and IgM levels to B. pahangi antigens were severely depressed in both athymic and Cy treated rats. IgG levels but not IgM levels were abrogated in CsA treated rats. These results implied that control of larval establishment or adult killing, and regulation of Mf levels are separate T-cell dependent mechanisms and act independently of IgG antibody. Control of Mf levels is associated with a specific IgM response which is Cy sensitive but CsA resistant. PMID- 1437227 TI - [The mid-growth spurt--a pre-puberty growth spurt. Review of its significance and biological correlations]. AB - The MGS is a growth phenomenon during early childhood, expressed by a mild transitory acceleration of growth velocity between five and eight years of age. It appears to be more pronounced in boys than in girls. It is probably caused by the functional maturation of the adrenals ("adrenarche") which leads to an increased androgen production during this age. Interactions with the pituitary growth hormone, also presenting with increased secretion rates at this particular period, are very probable. A hypothesis is offered for the explanation of individual differences and distinctness of the MGS. Although the MGS cannot be interpreted as a very first step of puberty, some additional biochemical facts suggest fundamental changes in the organism. Therefore, the MGS could be regarded as a "marker" within the biological development of the child. PMID- 1437232 TI - In vivo activation of macrophages by IFN-gamma to kill Entamoeba histolytica trophozoites in vitro. AB - To determine the role of interferon-gamma (IFN-gamma) in the activation of macrophages to kill Entamoeba histolytica trophozoites in vitro, C57BL/6 mice were injected with various doses of recombinant IFN-gamma (rIFN-gamma) by either the intravenous, intraperitoneal or intramuscular routes. Mice were treated with doses of rIFN-gamma ranging from 10(1) to 10(5) units. Twenty hours later, peritoneal macrophages were harvested from the treated animals. Macrophage monolayers were prepared and their in vitro cytotoxic activity against a virulent strain of E. hystolytica (IP:0682:1) was determined. Amoebicidal activity was determined by counting the number of dead trophozoites by Trypan Blue exclusion in cultures containing macrophages and amoebic trophozoites which were incubated together for 4 h. Both intravenous and intraperitoneal treatment resulted in the recovery of macrophages from the peritoneal cavity which exhibited amoebicidal activity in vitro. Peritoneal macrophages harvested from mice that had been treated intraperitoneally or intravenously with rIFN-gamma, however, showed significantly more amoebicidal activity in comparison to macrophages harvested from animals treated intramuscularly. There was a dose dependent relationship between the concentration of rIFN-gamma used to activate macrophages in vivo and the number of dead trophozoites in vitro. In addition, these results confirm our previous observations that treatment in vitro with rIFN-gamma can activate murine peritoneal macrophages to kill amoebic trophozoites. PMID- 1437229 TI - On the interaction between macrophages and developmental stages of Schistosoma mansoni: effect of muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) treatment on mice survival and the generation of schistosomulicidal macrophages. AB - Schistosomiasis is a chronic disease afflicting hundreds of millions of people throughout the world against which there is as yet no effective vaccine. In the present study we tested the effect of the immunomodulator muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) on the survival of Schistosoma mansoni infected mice and on the induction in them of schistosomulicidal macrophages. Mice exposed to 80 cercariae each and then treated with MTP-PE showed prolonged survival following either single or repeat infection. The treatment with MTP-PE, when initiated 70 days post the schistosome infection, diminished significantly the mortality of infected mice over an observed period of 110 days. In terms of treatment efficacy there was no evident difference between the intravenous and intraperitoneal mode of administration of the drug. MTP-PE treatment significantly reduced granuloma size and markedly diminished liver damaged as judged by the lower levels of alkaline phosphatase in the serum. Such treatment exerted no significant effect on the spleen or liver weight in infected mice nor on the worm burden resulting from either a single or double infection. In infected and non-treated mice, schistosomulicidal macrophages appeared after 8-10 weeks of infection. In infected mice treated with MTP-PE there was an accelerated appearance of such macrophages and these exhibited a greater cidal effect on the schistosomula. These immunostimulatory and life-prolonging effects of MTP-PE on S. mansoni-infected mice might indicate an effect of this reagent on cells involved in the granulomatous process. PMID- 1437231 TI - Transmission blocking immunity to human Plasmodium vivax malaria in an endemic population in Kataragama, Sri Lanka. AB - Serum effects on gametocyte infectivity, that is, transmission blocking/enhancing immunity, were measured in the sera of 196 acute Plasmodium vivax patients who were residents of a malaria region in Kataragama, southern Sri Lanka. Direct mosquito feedings were also performed on 170 of these patients. Sera of about 48% of patients suppressed gametocyte infectivity significantly (by more than 75%) and of a smaller proportion (12%) had pronounced infectivity enhancing effects. Transmission immunity did not increase with age of patients, rather, immunity tended to be higher in younger patients. Data suggest that immunity levels are boosted by reinfections only if they occur within a period of 4 months from the previous infection, i.e., that immune memory for boosting does not last beyond 4 months. Enhancing effects in the sera of patients correlated with the absence of gametocytes at the time of investigation suggesting that enhancement occurs early during the course of a blood infection, and blocking later, when serum antibodies reach higher levels. The blocking and enhancing effects of serum appears to depend not only on the antibody concentration in serum, but also on the intrinsic infectivity of the parasite isolate against which it is tested: thus, infectivity enhancing effects were potentiated by low intrinsic infectivities of the parasite isolate. The direct infectivity of patients to mosquitoes correlated with transmission immunity indicating that transmission immunity is an influential factor determining infectivity of malaria patients. PMID- 1437233 TI - Detection of cytokine mRNA in the brains of mice with toxoplasmic encephalitis. AB - C57Bl/10 ScSn mice infected with Toxoplasma gondii developed a meningoencephalitis, characterized by areas of tissue destruction and cellular infiltration including foci of neutrophils. Large numbers of cyst stages were found throughout the brain but were not always associated with inflammation. The use of immunocytochemistry to detect glial fibrillary acidic protein, an astrocyte specific marker, showed a widespread astrocyte activation. This was particularly prominent in areas of intense inflammation but cysts were negative for glial fibrillary acidic protein, indicating that astrocytes were not host cells for the bradyzoites. The use of the polymerase chain reaction to assist in the amplification of total brain RNA allowed the characterization of the cytokines being produced locally within the brains of infected animals. beta actin transcripts were detected in all of the uninfected and infected mice. In only one of the seven uninfected control mice were other transcripts found. Transcripts for tumour necrosis factor-alpha, interleukin-1 alpha and beta, interleukin-6, macrophage inflammatory protein-1 and interferon-gamma as well as the CD4 marker were detected in all of the infected mice. However, transcripts for IL-2 and IL-4 were not present. Several of the cytokines present are capable of initiating meningeal inflammation and may play a role in the immunopathogenesis of toxoplasmic encephalitis. PMID- 1437234 TI - Changes in the protein profile and antigenicity of different Borrelia burgdorferi strains after reintroduction to Ixodes ricinus ticks. AB - Eight Swiss strains of Borrelia burgdorferi, with various protein profiles and the North-American strain B31 were artificially introduced into Ixodes ricinus ticks and reisolated 10 days later. All isolates were subsequently examined by SDS-PAGE analysis. Comparing initial isolates with the reisolates, we observed that 7 out of 9 strains changed their protein pattern with respect to the major proteins OspA, OspB and the 22 kDa protein after passage in the tick. The strains NE2, NE4 and NE83 with the initial phenotype of OspA and 22 kDa proteins changed to the phenotype of OspA and OspB, the strains B2 and NE202 with the initial phenotype of OspA acquired an additional protein of 22 kDa and the strain NE58 with the initial phenotype of OspA also acquired a protein of 22 kDa. Examination of these isolates by Western blot analysis demonstrated that the reaction with the monoclonal antibody H5332 and a monospecific polyclonal antibody PoAb/anti-22 kDa differed between the initial isolates and the reisolates. PMID- 1437235 TI - The influence of challenge dose, duration of immunity, or steroid treatment on mucosal mast cells and on the distribution of sheep mast cell proteinase in Haemonchus-infected sheep. AB - The distribution of granule-specific sheep mast cell proteinase (SMCP), was assayed by immunocytochemistry and quantified by immunoassay in sheep immune to Haemonchus contortus. Repeated infection with Haemonchus larvae over 10-12 weeks induced a pronounced mucosal mastocytosis, including intraepithelial globule leukocytes (GL), which, 7 days after ceasing this dosing regime, was associated with the inability of incoming larvae to establish within the abomasal mucosa. Loss of this resistance, due to the cessation of stimulation with Haemonchus larvae 84 days previously or to treatment of sheep with corticosteroid, was associated with a marked decline in mast cell density and concentrations of SMCP in abomasal mucosal tissues. Nevertheless, larvae also failed to establish in immune sheep rested from challenge 42 days previously and in which mast cell counts were not significantly different from those of control sheep. A small, but significant, release of SMCP was demonstrated in gastric mucus from immune sheep following larval challenge, whereas little or no SMCP was detected in mucus from naive animals. PMID- 1437236 TI - Modulation of cytokine production and response phenotypes in murine trichuriasis. AB - BALB/K mice are usually resistant to infection with the intestinal nematode parasite Trichuris muris and exhibit a Th2 dominated (IL-5, IL-9) response. Conversely in B10.BR mice, which are unable to expel T. muris, Th1 type (IFN gamma producing) cells predominate. We have manipulated the course of infection in these two strains of mice such that the period of host-parasite contact is extended in the former and curtailed in the latter. Extension of host-parasite contact in BALB/K mice beyond normal (day 21) resulted in the modulation of cytokines produced by in vitro concanavalin A (Con-A) stimulated MLNC away from IL-5 and IL-9 (Th2-type cytokines) in favour of the Th1-type cytokine IFN-gamma. Curtailment of host parasite contact in B10.BR mice to less than 21 days resulted in elevated production of IL-5 and IL-9 by MLNC in the absence of elevated IFN gamma levels. Thus modulation of expulsion phenotype also modulates cytokine production by T-cells in the MLN draining the site of infection, with a Th2 response being associated with resistance and a Th1 type response with the inability to expel the parasite. Mechanisms by which the modulated cytokine profiles arise are discussed. PMID- 1437237 TI - Transmission blocking antibody of the Plasmodium falciparum zygote/ookinete surface protein Pfs25 also influences sporozoite development. AB - The Plasmodium falciparum zygote/ookinete surface protein, Pfs25, persists in the oocyst wall throughout its development. Anti-25 kD transmission blocking antibody, given to infected Anopheles stephensi or A. gambiae mosquitoes in an additional bloodmeal, 3-6 days after being fed gametocyte infected blood, penetrated the oocyst and reacted with the 25 kD protein within it. This reaction caused a significant reduction in the number of developing sporozoites. Mouse serum containing antibodies raised by immunization with a recombinant 25 kD yeast product showed a similar effect. PMID- 1437238 TI - An immunocytochemical test for the diagnosis of antibodies to Plasmodium vivax. AB - An immunocytochemical peroxidase test (ICPT) has been developed to allow serological measurement of the antibody response to Plasmodium vivax by light microscopy. Acetone fixed P. vivax erythrocyte stages were used as source of antigen. The immunofluorescent antibody test (IFAT) was used as reference test. In testing sera from individuals infected with P. vivax in southeastern Venezuela a high correlation (100%) was obtained between the ICPT and the IFAT. There were cross reactions with sera from patients with malaria by P. falciparum but not with those from patients with other parasitic diseases. Antibody titres as measured by the ICPT showed a positive correlation with past P. vivax malarial experiences. PMID- 1437239 TI - Occurrence and characteristics of hypodense eosinophils in rats infected with Trichinella spiralis. AB - Hypodense eosinophils are observed in peripheral blood and tissue from patients with eosinophilia due to helminthic infections. In this study, the variation in eosinophil density was examined in rats during Trichinella spiralis infection. Hypodense eosinophils were observed in the peripheral blood in association with Trichinella infection. In peritoneal fluid, which was representative of tissue fluid, a majority of eosinophils were hypodense regardless of the infection. During the course of tissue eosinophilia after the infection, there was a particular increase in the lowest dense cells in the population of hypodense eosinophils. Eosinophils with lower density, demonstrated larger diameters and had more potent cytotoxic activity. PMID- 1437240 TI - Inhibition of protein synthesis in irradiated larvae of Schistosoma mansoni. AB - UV-irradiated and gamma-irradiated schistosomula of Schistosoma mansoni induce high levels of resistance to challenge infection in experimental hosts. It was observed that both types of irradiation severely inhibited protein synthesis by the parasite larvae. Schistosomula were treated with the metabolic inhibitor actinomycin D to simulate this effect of irradiation. The ability of these drug treated larvae to induce immunity was tested in animal protection experiments. Our results suggest that inhibition of protein synthesis may help to generate the enhanced immunogenicity of irradiated schistosomula. In explanation, we propose that irradiated schistosomula may be such potent immunogens because they express antigens in disrupted, abnormal conformations. Inhibition of protein synthesis may both directly create such modified antigens, and also ensure that they persist and accumulate for presentation to the host immune system. PMID- 1437241 TI - Demonstration of Leishmania specific cell mediated and humoral immunity in asymptomatic dogs. AB - An ELISA and a lymphocyte proliferation assay were used for the detection of anti Leishmania antibodies and parasite specific cellular immunity respectively in a preliminary study of canine leishmaniasis in Oporto, Portugal. A high rate of infection was found considering the comparatively small group sampled. Of 34 dogs examined two had anti-leishmanial antibodies but their lymphocytes did not proliferate in the presence of Leishmania infantum. Conversely two dogs demonstrated antigen specific lymphocyte proliferation in the absence of any detectable anti-parasite antibodies. To our knowledge this is the first time that cellular immunity and presumably resistance of dogs to leishmanial infection has been demonstrated. These results suggest that there may be a spectrum of canine leishmaniasis similar to that observed in the human disease. PMID- 1437242 TI - Antibody-dependent cell-mediated immune reactions to Loa loa microfilariae in amicrofilaraemic subjects. AB - Antibody-mediated mechanisms that could be important in controlling microfilaraemia in Loa loa infected amicrofilaraemic adults (mf-ve) were studied. These subjects were selected as having a verified ocular passage of an adult L. loa but being amicrofilaraemic and without recent diethylcarbamazine treatment. Sera from 37 mf-ve subjects were compared to 14 sera from heavily (greater than 4000 mf/ml) infected subjects (mf+ve) and 9 sera from Caucasian control subjects for their reactions with L. loa mf (mf). Many mf-ve sera (22/37) were strongly positive in immunofluorescence (IFAT) on living mf. Mf+ve sera were negative, or only weakly positive, and Caucasian sera were negative. Clinical signs were not significantly different between IFAT reactive and non-reactive mf-ve subjects. Approximately half of the IFAT positive, mf-ve sera were also able to agglutinate mf; no other sera were active in this test. Titres ranged from log2 3-6 and in most cases, 9/11, the agglutination reaction was mercaptoethanol-sensitive. Antibody-dependent cellular adherence was studied using mf and leukocytes from uninfected donors. Using cryopreserved mf many heat-inactivated mf-ve sera gave strong reactions with obvious adherence by 4 h and few motile mf remained by 16 h but when fresh mf were employed these reactions were weak. However, addition of complement to many (10/11) mf-ve sera considerably enhanced adherence to fresh mf. The effect of various treatments on the complement source indicated a role for both the classical and alternative pathways. The cells attached to mf were mainly neutrophils (83%) with some eosinophils (15%) and few mononuclear cells (2%). The common occurrence of antibodies able to mediate complement-dependent adherence of polymorphonuclear leukocytes to L. loa mf in the sera of mf-ve subjects may indicate that such a mechanism is important in controlling microfilaraemia in vivo. PMID- 1437243 TI - The influence of adjuvant on humoral responses to glutathione-S-transferase fusion proteins. AB - Mice were immunized with one of two Schistosoma mansoni antigens, Sm20 and Sm50, expressed as fusion proteins with Schistosoma japonicum 26,000 Dalton glutathione S-transferase (GST) or with GST alone. Antibody responses to GST were shown to be critically dependent on the adjuvant used. In Sm20-GST immunized mice, we noted a striking bias to respond either to Sm20 or to GST according to the adjuvant used and responses to both in the same individual were rare. Fusion with Sm50, which is relatively non-immunogenic, appeared to down-regulate responses to GST. PMID- 1437244 TI - The operative treatment of scoliosis in Duchenne muscular dystrophy. PMID- 1437245 TI - The Thurstan-Holland fragment. PMID- 1437246 TI - Management of open fractures. AB - An open fracture is an orthopaedic emergency that can lead to devastating complications and prolonged rehabilitation. The goals of treatment are to prevent infection, achieve bone union, and restore function. The treatment should involve the use of antibiotics, repeated thorough irrigation and debridement, early fracture stabilization, early wound closure, and aggressive rehabilitation. The result of treatment is largely affected by the initial soft-tissue loss, wound contamination, fracture stability, and neurovascular status. PMID- 1437247 TI - 2-D and 3-D computed tomography and magnetic resonance imaging in developmental dysplasia of the hip. AB - Clinical examination and plain roentgenograms have been the main methods of diagnosis and treatment of developmental dysplasia of the hip. Occasionally, concentric reduction cannot be achieved, or the reduction is questionable. A dynamic arthrogram can add more information but is usually performed under general anesthesia. "Mini" computed tomographic imaging demonstrates the femoral head-acetabulum relationship more accurately and produces minimal radiation. Three-dimensional computed tomography is useful in older children, in whom all sections are ossified. Magnetic resonance imaging, particularly 3-D magnetic resonance imaging, demonstrates the nonossified structures. It is the best method of visualization in developmental dysplasia of the hip. The disadvantages of this method include its cost and the lack of dynamic imaging. In the future, new software will overcome these shortcomings. PMID- 1437249 TI - Clinical experience with unreamed locked nails for open tibial fractures. AB - Open fractures of the tibia remain a formidable injury. External fixation has been the mainstay of treatment for the more severe fractures. This treatment option, however, is not without significant complications. Of particular importance is the rate of infection once the fixator is converted to a reamed intramedullary nail in cases of delayed union or nonunion. A retrospective review of the records of 20 patients who underwent unreamed, interlocked, intramedullary nailing for tibial fracture has shown that unreamed tibial rodding offers an excellent alternative to external fixation for the management of Grades I and II open tibial fractures. Additionally, for Grade III open fractures, this serves as an excellent form of preliminary stabilization, allowing the soft-tissue injury to heal. PMID- 1437248 TI - Plaster cast versus Clyburn external fixation for fractures of the distal radius in patients under 45 years of age. AB - In this prospective study, 70 patients between the ages of 20 and 45 years with comminuted intra-articular fractures of the distal radius of types III to VIII (graded according to Frykman) were treated either by closed reduction and forearm plaster (35 patients) or by application of a Clyburn dynamic external fixator (35 patients). The external fixator was more effective at holding the manipulated position, and the roentgenographic loss of position during fracture union was minimal compared with that seen in patients treated in plaster. Functional results in the fixator group were 18 excellent, 10 good, 6 fair, and 1 poor. The plaster group showed the following functional results: 12 excellent, 8 good, 10 fair, and 5 poor. The external fixator generated significantly better anatomical and functional results than did treatment with forearm plaster. A good anatomic position combined with early rehabilitation of the wrist function produced very favorable functional results in patients less than 45 years of age. PMID- 1437250 TI - Compartment pressures of the leg following intramedullary fixation of the tibia. AB - A prospective study was performed to determine whether compartment pressures of the leg were affected by intramedullary fixation of the tibia. Ten of the 11 patients studied had surgery for acute diaphyseal fractures and 1 for tibial nonunion. Compartment pressures were measured immediately prior to the procedure and at 12 hours after the procedure. There was no difference between the preoperative and postoperative compartment pressures. Our data suggest that intramedullary stabilization of the tibia does not predictably increase compartment pressures. PMID- 1437251 TI - Scaphoid enchondroma. AB - Enchondromas are rarely found in carpal bones. This paper reports a case with scaphoid enchondroma and reviews three cases from previous literature. Three of the patients with scaphoid enchondromas presented with pathologic fractures after traumatic events. Each enchondroma had characteristic histopathologic findings. It is important to realize that although enchondroma is usually a painless lesion, it weakens the cortex of the involved bone, facilitating fracture. Thus, when cystic scaphoid fractures are encountered, enchondroma must be part of the differential diagnosis. PMID- 1437252 TI - Technical tips for the fixation of supracondylar femur fractures with the sliding screw-plate device. AB - Supracondylar fractures of the femur are common injuries. When open reduction and internal fixation are required, these fractures become challenging problems. We present four technical tips that help the surgeon obtain good results when open reduction and internal fixation with the screw- and side-plate device are chosen. PMID- 1437253 TI - A 35-year-old man with right wrist pain. AB - The following is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. The initial history, physical findings, and roentgenographic examinations are found on this page. The final clinical and roentgenographic differential diagnoses are presented on the following pages. PMID- 1437254 TI - The role of calcitonin treatment in postmenopausal osteoporosis. AB - Synthetic salmon calcitonin (SCT) is a potent antiosteoclastic hormone with adjunctive stimulatory effects on osteoblastic function. It is capable of increasing or stabilizing bone mass in osteoporosis and thereby can lessen the risk of fractures. Treatment doses vary from 100 IU daily to 50 IU three times a week, and the duration of treatment is 2 to 5 years. SCT also exerts an analgesic effect on the skeleton that increases its beneficial effect. Side effects, which do not involve organ toxicity, are common but are usually mild and transient. More severe side effects can be managed by maneuvers such as bedtime dosing, premedication, and temporary dose reduction. Primary resistance occurs in approximately 25% of patients and secondary resistance, usually due to neutralizing antibody formation, in 10% to 20% of patients. SCT is indicated in both early and late osteoporosis and is the treatment of choice in the latter. PMID- 1437255 TI - Elbow arthroscopy. AB - Elbow arthroscopy has made rapid advances in recent years. The improvement in the arthroscopic technique, as well as the development of technically advanced equipment, has made elbow arthroscopy very attractive to orthopaedic surgeons. It is important to realize that elbow arthroscopy is a modality that should be respected. This demanding procedure requires keen awareness of the elbow's anatomy and the technical arthroscopic approach to the elbow joint. With this careful approach in mind, the orthopaedist will find that elbow arthroscopy can be a valuable tool. PMID- 1437256 TI - Femoral allograft reconstruction in revision total hip arthroplasty. AB - Rigid graft fixation with cortical loading through the graft to protect from stress shielding is an important goal during femoral allograft reconstruction in revision total hip arthroplasty. Total proximal femur allografts require intramedullary prosthetic splinting and a step-cut osteotomy or extended lateral allograft plate for the most secure fixation and ultimate union. Nonunion and dislocation are the most critical complications, and infection rates are similar to other reconstruction procedures. This review discusses the principles and application of allografts in femoral revision total hip arthroplasty. PMID- 1437257 TI - The current status of acetabular fixation in total hip replacement. AB - Aseptic loosening of the acetabular component is the major long-term complication of cemented total hip replacement. In this article, the improvements in cementing technique and cemented acetabular component design, as well as the evolution of noncemented acetabular cups, are reviewed. The porous-coated acetabular component has emerged as the state of the art in both primary and revision hip arthroplasty. Current trends in porous cup design and implantation are presented. The ultimate fate of the porous ingrowth cup will be based on long-term clinical and roentgenographic follow-up studies. PMID- 1437258 TI - Laser arthroscopy. AB - Lasers have become widely used in several medical and surgical disciplines. In ophthalmology and plastic surgery, their use has permitted the development of therapeutic modalities that would have been otherwise impossible. In such specialties as gynecology and general surgery, lasers provide advantages that make certain procedures more convenient and easier to perform. In contrast, orthopaedic surgeons have, to date, been slow to accept these devices into the therapeutic armamentarium. The purpose of this paper is to describe the status of laser use in the orthopaedic subspecialty of arthroscopy. PMID- 1437259 TI - Transient osteoporosis of the hip misdiagnosed as osteonecrosis on magnetic resonance imaging. AB - A 34-year-old man developed idiopathic, bilateral, asynchronous transient osteoporosis of the hip. The symptoms included hip pain with activity, and roentgenography revealed osteoporosis of the femoral head and neck. Radionuclide bone scans showed increased uptake of the involved femoral head. Magnetic resonance imaging (MRI) early after the onset of right-side symptoms was characterized by decreased signal intensity on T1-weighted images and patchy areas of increased and decreased signal intensity on T2-weighted images; this was initially interpreted as being consistent with osteonecrosis. Despite evaluation by multiple physicians and imaging methods, including MRI, the correct diagnosis of transient osteoporosis of the hip was delayed until after resolution of the syndrome. Transient osteoporosis of the hip should be included in the differential diagnosis of hip pain. PMID- 1437260 TI - Long-term follow-up of a total articular resurfacing arthroplasty and a cup arthroplasty in Gaucher's disease. AB - Patients with Gaucher's disease, a well-described lipid storage disorder with many systemic manifestations, often present to the orthopaedic surgeon with osteonecrosis of the femoral head. This can be a difficult orthopaedic problem because of the patient's young age at presentation and abnormal bone stock. Review of the literature leaves uncertainty as to the ideal treatment of femoral head avascular necrosis in this disease. This article reports the long-term results of a cup arthroplasty and a total articular resurfacing arthroplasty procedure for bilateral hip involvement. In light of the less-than-satisfactory results of total hip arthroplasty for young patients with Gaucher's disease, resurfacing arthroplasty may warrant more serious consideration. For the older patient with Gaucher's disease, total hip arthroplasty may be preferable. PMID- 1437261 TI - An 80-year-old man with symptoms of bilateral carpal tunnel syndrome. PMID- 1437262 TI - Removal of broken distal interlocking screws. AB - Existing techniques for removing broken distal interlocking screws can involve trephine over-cutting of the screws, which requires bone exposure and creates larger stress risers by enlarging the original screw hole. We present a technique for removal of these screws that takes advantage of both the design of interlocking screws and the bone quality in the area of their placement. In this technique, a guide-wire "punch" is used to drive the screws through the medial cortex and soft tissue for removal through a small medial incision. PMID- 1437263 TI - Significance of osteoporosis: a growing national health care problem. PMID- 1437264 TI - Negative extension sign in a patient with a herniated lumbar disc. PMID- 1437265 TI - Evidence for the existence of ganglioside molecules on Pneumocystis carinii from human lungs. AB - This study was undertaken to assess whether glycolipid antigens (particularly gangliosides) are associated with Pneumocystis carinii obtained from human lungs. Gangliosides were extracted, purified in high performance thin-layer chromatography and stained with resorcinol. Two resorcinol-positive bands, co migrating with GM1 and GD1a were demonstrated, suggesting the existence of ganglioside molecules on P. carinii. No resorcinol-positive bands were revealed in the pulmonary control tissue. In addition, an antiserum obtained from rabbits immunized with P. carinii antigen reacted with gangliosides GM1 and GD1a, as revealed by a dot immunobinding assay. This reactivity was inhibited by first incubating the antiserum with ganglioside micelles. Furthermore, anti glycosphingolipid antibodies (aGM1) reacted with the bands of 200 and 55 kDa of P. carinii antigen. These results suggest that ganglioside antigens expressed on P. carinii can trigger specific immune responses. PMID- 1437266 TI - Vegetation structure influences the burden of immature Ixodes dammini on its main host, Peromyscus leucopus. AB - To determine whether the relative abundance of immature Ixodes dammini (the vector of Lyme disease and human babesiosis) is related to habitat structure, we examined tick burdens on their main host, the white-footed mouse (Peromyscus leucopus), in 4 structurally diverse sites on Great Island, Massachusetts, USA. Vegetation structure at each site was quantified with respect to 25 habitat variables. Principal components analysis was used to reduce this set of habitat variables to seven new and orthogonal variables. Immature tick abundance varied widely among grids. Regression analysis of tick burdens on the habitat principal components showed that larval burdens were related strongly to the density of woody vegetation and negatively to herbaceous vegetation. Nymphal burdens were related negatively to herbaceous vegetation, but the relationship was not as strong as in the case of larvae. An experimental reduction in the abundance of white-tailed deer (Odocoileus virginianus), the main host of adult ticks, substantially reduced tick burdens and altered their relationships to habitat structure. Nymphal burdens were unrelated to habitat structure following deer removal. Manipulating habitat structure may have utility as a control strategy against this important vector. PMID- 1437267 TI - Trichinella strain, pig race and other parasitic infections as factors in the reliability of ELISA for the detection of swine trichinellosis. AB - An enzyme-linked immunosorbent assay (ELISA) using crude worm extracts (CWE) and mixtures of these as antigens of five Spanish isolates (P, C, B1, B2 and W) was developed for detecting homologous and heterologous experimental infections with these isolates between-14 and 82 days post-infection (p.i.) in white and Iberian pigs. A total of 243 pigs (Iberian or cross-bred with this race) with numerous parasitic infections were also screened for the presence of antibodies to a mixture of CWE of C, B1 and B2 isolate. The test showed a specificity of 93.1 98.9% depending on the cut-off values and a maximum sensitivity of 92.8-100% between days 34 and 82 p.i. A low grade of infectivity was shown in the T3 isolates compared to the T1 isolates (P, C, B1 and B2) but high cross-reactions were observed between all the isolates with minor differences between P and W isolates. The highest antibody response was found in P infections and the lowest in pigs infected with the W isolate. A clear association between the presence of several parasitic infections and false positive reactions was not found, but an important relation was shown between high background levels and the Iberian race in experimentally and conventionally raised pigs. PMID- 1437268 TI - Genetic influences upon eosinophilia and resistance in mice infected with Trichinella spiralis. AB - Genetic influences upon host variation in eosinophilia and resistance to helminth infection, and the relationship between these parameters, were investigated in 7 inbred and 1 hybrid strains of mice infected with Trichinella spiralis. Clear strain-dependent variations were observed in the maximum peripheral blood, bone marrow and spleen eosinophilia attained in infected animals. SWR, NIH and SJL strains of mice all gave high responses to infection; four congenic strains sharing the B10 background (C57BL10 [B10], B10.S, B10.G and B10.BR) were low responders. Some of the genes for high responsiveness appeared to be dominant, as F1 hybrids from high- and low-response phenotype parental strains showed intermediate to high responses to infection. Intestinal eosinophilia showed no correlation with either peripheral blood or bone marrow responses (NIH and B10 strains having similar levels of eosinophil response in gut tissue) and was unrelated to the level of resistance to infection. Whereas NIH were highly resistant, with adult worm burdens at 13 days post-infection and muscle larval burdens at 35 days post-infection significantly lower than all other strains, B10 were quite susceptible, retaining substantial worm burdens at day 13 and harbouring large numbers of muscle larvae. Measurements of the level of the eosinophilopoietic cytokine IL-5 in sera during infection showed that the two strains differed in the kinetics of release but not in their absolute capacity to produce this cytokine. NIH mice released high levels during a primary infection, B10 released high levels during a secondary infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437269 TI - Variation in responsiveness to Trichinella spiralis infection in inbred rat strains. AB - An analysis of interstrain variation between 12 inbred and 4 congenic rat strains in the expression of immunity against Trichinella spiralis is reported. All rat strains expressed strong rapid expulsion which resulted in the elimination of 88 98% of a challenge infection of muscle larvae. In contrast, substantial interstrain variation in the rate of adult worm expulsion in the primary infection was evident. By day 10 after infection, BUF and YO strains had less than 50 worms left in the intestine whereas BI and WKA strain rats had barely begun rejection, with approximately 1000 worms present in the gut for both strains. All other rat strains fell within these extremes in a continuous gradation. There was no clustering of rat strains into phenotypic groups with comparable worm burdens as seen with mice. The number of muscle larvae that established after the primary infection showed less variation than had adult worm burden in the primary infection and there was only a weak correlation of muscle larvae burden with numbers of intestinal adults present at 10 days. Comparison of MHC-matched or MHC-disparate rat strains on a PVG background suggested that non MHC genes determined the principal adult worm rejection characteristics of a given strain. The absence of phenotypic variation in the expression of rapid expulsion in rats reinforces the biological distinction between rat rapid expulsion and the 'rapid expulsion' defined for mice. PMID- 1437270 TI - The effects of age, temperature, light quantity and wavelength on the swimming behaviour of the cercariae of Cryptocotyle lingua (Digenea: Heterophyidae). AB - Laboratory experiments indicated that the active life-span of the cercariae of Cryptocotyle lingua was temperature-dependent. An increase in water temperature and population age both correlated with a tendency for the organisms to become decaudate. The larvae were strongly photoresponsive to lateral light but with time, horizontal swimming rates (HSRs) from release point to light source progressively declined. When measured over a range of light quantities, HSRs peaked at 30 microM/m2/s. HSRs were also influenced by water temperature. A rapid increase occurred up to 15 degrees C after which there was a precipitous decline. HSRs to coloured light were negatively correlated with increasing wavelength. When offered a choice between colours, cercariae favoured the shorter wavelengths. The implications of these responses for successful transmission are discussed. PMID- 1437271 TI - Protein content of CBA/Ca mouse diet: relationship with host antibody responses and the population dynamics of Trichuris muris (Nematoda) in repeated infection. AB - The influence of host dietary protein on acquired immunity and intestinal helminth population dynamics during repeated infection was studied using the mouse-Trichuris muris experimental model. CBA/Ca mice fed a 2% (by mass) protein diet ad libitum maintained body weight during the experiment, but when fed diets containing either 4% or 16% (by mass) protein gained weight steadily. Infection with T. muris did not affect the growth of the latter mice but significantly reduced the growth of animals fed on the 2% protein diet. When repeatedly infected with either 5 or 50 eggs every 10 days, the mice fed the 2% or 4% protein diet accumulated adults in proportion to infection dose. The results show that this is due to both the establishment of larvae at each repeated infection and the survival of established adults. In contrast, very few worms were recovered from animals fed the 16% protein diet, principally as a result of the development of strong acquired immunity to reinfection. T. muris egg output/mouse increased with infection dose in animals fed the low protein diets, but no parasite eggs were detected in the faeces of hosts fed the 16% protein diet. Mouse antibody responses to adult worm excretory/secretory antigen were time- and infection dose-dependent in all 3 dietary groups. The major finding was that the specific antibody response was more intense, both quantitatively (serum OD levels) and qualitatively (antigen recognition by IgG1), in mice fed the low protein diets, even though they remained susceptible to infection. This study shows that host dietary protein deficiency, even at levels irrelevant to normal growth, can markedly potentiate the transmission of T. muris via alterations in host resistance. The high levels of antibody in susceptible animals suggest that this defect in resistance is unlikely to be due to nutrient deficiency-associated defects in humoral immunity. PMID- 1437272 TI - Effect of intra-erythrocytic magnesium ions on invasion by Plasmodium falciparum. AB - Exclusion of magnesium ions from resealed ghosts or their extraction from intact human red cells by means of an ionophore results in a reversible drop in susceptibility to invasion by Plasmodium falciparum merozoites in vitro. Resealed ghosts, containing magnesium-ATP and diluted cytosol, are invaded with high efficiency only when the original hypotonic lysis is carried out in the presence of magnesium ions. This effect is not related to the loss of membrane-associated constituents when magnesium ions are absent. Ghosts containing calcium ions, together with the protective agent, flunarizine, were essentially resistant to invasion; this effect is again at least partially reversible. A possible explanation of these phenomena is that entry of the merozoite may be inhibited by breakdown of the host cell phospholipid asymmetry, with the appearance of aminophospholipids at the outer cell surface. PMID- 1437273 TI - Comparative prevalences of Ascaris lumbricoides, Trichuris trichiura and hookworm infections and the prospects for combined control. AB - Programmes to control Ascaris lumbricoides, Trichuris trichiura and hookworm infections have often been targeted at each infection separately, but the advent of benign and broad-spectrum anthelmintics suggests that combined control may be feasible. The extent to which the infections co-occur in communities will determine the need for, and potential benefits of, such a combined approach. This paper examines the comparative distribution of the three geohelminths in different geographical areas and shows that A. lumbricoides and T. trichiura have closely related distributions, while hookworm infection is largely independent of the other two. These results indicate that many communities are at risk of disease from infection by more than one species of helminth. The similar distributions and epidemiological characteristics of A. lumbricoides and T. trichiura suggest that simultaneous control of these two parasites by the same strategy would be feasible and highly beneficial to communities. Multiple species control strategies which aim to control hookworm infection may require a more complicated protocol with more precise locality targeting. PMID- 1437274 TI - Epidemiology of canine leishmaniasis: prevalence, incidence and basic reproduction number calculated from a cross-sectional serological survey on the island of Gozo, Malta. AB - Assessment of the resilience of canine leishmaniasis to control or, more ambitiously, the effort needed to eradicate infection, requires an estimate of the basic case reproduction number (R0). This paper applies the theoretical results of Hasibeder, Dye & Carpenter (1992) to data from a cross-sectional survey on the Maltese island of Gozo in which dogs of known age, sex and occupation (pet, guard etc) were subjected to three different serological tests for the presence of specific antibody (IFAT, DAT and ELISA). Difficulties in interpreting these test results, and hence of determining the proportion of dogs infected, present the main obstacle to estimating R0: estimates are critically dependent on the choice of threshold separating seropositives from seronegatives. The data do, however, allow a robust comparative analysis of risk which shows that the force of infection experienced by working dogs is about three times higher than that of pet dogs, a degree of non-homogeneous contact which actually has little effect on estimates of R0. We suggest a cautious point estimate of R0 congruent to 11, and comment briefly on its significance for leishmaniasis control. PMID- 1437275 TI - Mathematical modelling and theory for estimating the basic reproduction number of canine leishmaniasis. AB - The paper describes a mathematical model for canine leishmaniasis and presents formulae which can be used to estimate the basic reproduction number, R0. The primary concern has been to devise methods of estimation which make best use of those data most easily obtained by fieldwork, e.g. surveys of prevalence in dog (by age) and sandfly populations. A range of formulae are offered which are more or less demanding of data, and which consequently give more or less precise estimates of R0. They include methods for assessing the influence on R0 of heterogeneous biting rates of sandflies on dogs, in which the essence of heterogeneous transmission can be captured merely by measuring relative rather than absolute contact rates. PMID- 1437276 TI - Adhesion of Trichomonas vaginalis to plastic surfaces: requirement for energy and serum constituents. AB - The ability of Trichomonas vaginalis to adhere to plastic surfaces in the presence of various agents and under different growth conditions was examined in wells of microtitre plates containing unsupplemented TYI medium or the same, with various supplements. Following incubation, the wells were thoroughly washed and adhesion was determined by microscopic counting of the adherent organisms. There was no detectable adhesion in the absence of both serum and carbohydrate. Optimal adhesion (about 10-20% of the total number of parasites) was obtained throughout the growth curve in culture media supplemented with either serum or serum Cohn fractions IV-I (rich in alpha-globulin) or IV-4 (rich in alpha + beta-globulin) and 25 mM glucose, maltose or fructose, but not in plates pre-coated with the Cohn fractions. Cohn fraction II + III (rich in beta + gamma-globulin) moderately enhanced adhesion while Cohn fractions II (rich in gamma-globulin) or V (albumin), fibronectin, Tamm-Horsfall glycoproteins and polylysine were without effect. Non-metabolizable sugars (methyl derivatives of glucose, mannose or fucose) did not support growth, but, surprisingly, enhanced adhesion. At 4 degrees C, the trichomonads were not able to adhere and pre-adherent organisms detached from the plastic surface. Optimal adhesion was obtained at a pH range of 6.5-7.5 but was already detectable at pH 5.5. Cytochalasin E markedly suppressed adhesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437277 TI - Schistosoma mansoni: adult males and females differentially express antigens encoded by repetitive genomic DNA. AB - Two repetitive DNA sequences have been characterized from Schistosoma mansoni which were transcribed into mRNAs and translated to give two families of cross reactive proteins. One DNA element, which was present as a 230 bp Pst I fragment was arranged in tandem arrays of at least 17 copies in the genome. The second element, which could be localized to a 1800 bp Pst I fragment, was dispersed in the genome. The 1800 bp repeat was found on the mRNA encoding the 45 kDa polypeptide precursor of a potential surface antigen. This precursor was post translationally modified to give a 50 kDa antigen (Sm50) which was expressed from the cercaria to the adult worm and in the egg. However, a proportion of this antigen was differentially modified in females and eggs to give a 60 kDa form. Two copies of the 230 bp repeat and one copy of the 1800 bp repeat were found on a second cDNA clone. The antiserum raised against the fusion protein of this clone recognized a family of cross-reactive proteins ranging from 14 to 70 kDa in size. The members of this family were also differentially expressed between the sexes. Consequently, two families of antigens have been identified which were both encoded by repetitive DNA elements and whose members were both differentially expressed in adult male and female worms. PMID- 1437278 TI - Immunization against cerebral pathology in Plasmodium berghei-infected mice. AB - The development of cerebral lesions in Plasmodium berghei-infected mice was dependent on the strain of mice and the size of the infectious inoculum. In particular, C57Bl/6J mice develop cerebral lesions when infected with low numbers of parasitized erythrocytes. By increasing the number of parasites in the infectious inoculum, the percentage of animals that develop cerebral malaria is decreased. Varying degrees of protection against the development of cerebral malaria can be obtained by several methods of immunization. (1) Injection of mice with large numbers of disrupted parasitized erythrocytes 1 or 2 weeks before the challenge infection (protection up to 70%). (2) A 2-day immunizing infection given 9 or 14 days before the challenge infection (protection up to 85%). (3) Injection of mice with plasmodial exoantigen preparations 1 week before the challenge infection (variable protection-rate, up to 100%). In all mice protected against cerebral malaria, parasitaemia is not affected by the immunizing treatment, indicating that protective mechanisms against cerebral malaria and parasitaemia are independent. PMID- 1437279 TI - Fluorescent lipid uptake and transport in adult Schistosoma mansoni. AB - Fluorescent lipophilic compounds can be used to label the surface membrane of Schistosoma mansoni by adding the compound in small amounts of organic solvents to aqueous medium in vitro. Under these conditions it is difficult to follow routes of distribution of the label. Here we have absorbed nitrobenzoxadiazolamine methylamino-(NBD)-ceramides to positively charged Dowex beads, and incubated the labelled beads with living parasites. The NBD-ceramide transfers to the surface membrane as a patch 50-100 microns in diameter, after which the label can be seen localized in the gut and in a very concentrated form in organelles within the oesophageal gland cells. Subsequently the labelled compound can be found in organelles within other body cells, including subtegumental cells. We show that the labelled ceramide has been transported from the patch in the surface membrane through internal membrane systems to the destination in the gut and oesophageal gland and not transported through the gut via the external medium. A different pattern was observed when NBD-cholesterol was used. The pharynx was rapidly labelled when NBD-cholesterol was added in medium with or without serum or attached to red blood cells only. Diffuse labelling of the surface membrane and oesophageal gland occurred. We have demonstrated a novel route of lipid transport within the parasite. The route requires the surface membrane to have very specialized regions to facilitate such transport. PMID- 1437280 TI - Kinetic modelling of isometamidium chloride (Samorin) uptake by Trypanosoma congolense. AB - Clones of Trypanosoma congolense which express resistance to the widely used trypanocide isometamidium chloride accumulate less of the drug than clones which are sensitive to drug treatment. A mathematical model has been developed which was able to predict theoretical lines representing the uptake kinetics in trypanosomes which were sensitive to isometamidium, as well as for resistant trypanosomes in which reduced accumulation was a result of either reduced uptake or enhanced efflux of the drug. Data from drug uptake experiments were then fitted to these theoretical lines. While the value for drug efflux could not be separated from the dissociation constant of the trypanosomes for isometamidium, it was demonstrated that reduced accumulation is not a result of reduced uptake of isometamidium by drug-resistant trypanosomes. PMID- 1437281 TI - Sequence differences between histones of procyclic Trypanosoma brucei brucei and higher eukaryotes. AB - Four histones, a, b, c, d from procyclic Trypanosoma brucei brucei, which show similarities with the amino acid composition of the core histones H3, H2A, H2B and H4, were isolated and cleaved with Endoproteinase Glu-C. The fragments were separated by FPLC reversed phase chromatography and a subset of the fragments (a5, a9, b6, c8, d3, d9, d11) was subjected to sequence analysis. A 54-71% identity was found in the sequences of the fragment c8 and the C-terminal half of H2B and of three fragments of protein d covering the N-terminal half as well as the C-terminal region of H4. The amino acid sequence of the fragment a9 showed a 57 and 54% identity with H3 sequences of Saccharomyces cerevisiae and Xenopus laevis. Neither the a5 nor the b6 sequence could be aligned with histone sequences of other eukaryotes. The significant differences of 21-48% between the T.b. brucei histone sequences and those of calf thymus histones, which are more pronounced than the differences of Tetrahymena pyriformis and the higher eukaryote, resulted partially from replacements of amino acids with different properties and indicate specific patterns of histone-histone and/or histone-DNA contact sites in the nucleosome of T.b. brucei. These differences, together with the lack of a functional histone H1, may be sufficient to explain the lack of a salt-dependent formation of the nucleosome filament into the 30 nm fibre, which reflects alternative methods of organizing and processing the genetic information in the nucleus of the protozoan parasite and which may be of chemotherapeutic significance. PMID- 1437282 TI - The spectrum of presentation at autopsy of myocarditis in infancy and childhood. AB - To characterize the clinicopathological presentation of patients with myocarditis coming to autopsy in childhood, 32 cases of histologically-proven myocarditis were obtained from the files of the Adelaide Children's Hospital. In 16 of the cases (Group A), myocarditis was the only significant finding and death was ascribed to this condition. In the remaining 16 (Group B) myocarditis was found in association with other severe disease processes. Clinical histories of the 2 groups showed sudden death to be a feature in 5 out of 16 cases in Group A, 3 of whom had no prodromal symptoms. Five patients in Group B also suffered sudden death, but this was associated with a variety of causes, including bronchopneumonia, and asphyxia. These cases demonstrate the variability in clinicopathological presentation of myocarditis in infancy and childhood and suggest that myocarditis should always be considered a possible diagnosis at autopsy in the pediatric age group, even in the presence of coincident lethal disease. PMID- 1437283 TI - Parosteal lipomas: a new perspective. AB - Parosteal lipomas, benign adipose tissue tumors situated directly on bone cortex, are unusual neoplasms that appear to emerge from multidirectional mesenchymal "modulation" within the periosteum. These tumors have been described as "periosteal lipomas", "chondrolipomas of soft tissue" and "lipomas of nerves" but they are most commonly believed to originate from the periosteum. Although over 100 of such tumors have been described in the literature, they have not been the subject of a comprehensive review, nor their potential for chondroid modulation and enchondral ossification emphasized. A review of 14 parosteal lipomas from the Bone Tumor Registry, Armed Forces Institute of Pathology, indicates these tumors are frequently associated with chondroid and/or osseous modulation, which permits subclassification into 4 distinct variants. Each of the 4 subtypes (I: No Ossification; II: Pedunculated Exostosis; III: Sessile Exostosis; IV: Patchy Chondro-Osseous Modulation) is illustrated to demonstrate the morphologic basis for radiologic/pathologic correlation and subclassification. A brief overview of the literature and pathogenesis of this unusual lesion is presented and discussed. PMID- 1437285 TI - Delayed rupture of spontaneous tear of the ascending aorta--report of two fatalities. AB - A spontaneous tear of the ascending aorta, with or without medial dissection, can cause sudden death from hemorrhage due to aortic rupture. Two representative cases are described. Review of the clinical history and pathological changes showed that the terminal event was delayed allowing healing and reactive changes to occur in the aortic wall. A pathologist confronted with a fatal case of aortic rupture should be aware that death is not always immediate. Recognition of this has medicolegal importance, particularly if medical management is questioned because of a missed clinical diagnosis. PMID- 1437284 TI - Combined pathological and radiological study of the effect of atherosclerosis on the ostia of segmental branches of the abdominal aorta. AB - A combined pathological and radiological study of descending aortae from 15 subjects from 2 to 80 yrs of age was conducted to investigate changes in the segmental vessels with advancing aortic atherosclerosis. There were (i) small hillocks of musculo-elastic intimal thickening adjacent to the apex (centre of the flow divider) in the ostia of the segmental vessels in young subjects, (ii) progressive intimal thickening, distortion and narrowing of the ostia of the segmental vessels (iii) obliteration or loss of some ostia in advanced atherosclerosis of the distal abdominal aorta and (iv) gross discrepancy in severity of atherosclerosis between the aorta and its branches, the intimal proliferation tapering rapidly in the branches and often being minimal in the outer part of their intramural courses. Distal ramifications exhibited occlusions which radiographically were probably embolic or possibly artifactual. Atherosclerosis was rarely of significant degree histologically within the proximal 2 cm of the segmental branches. PMID- 1437286 TI - A prospective study of the morphological aspects of tumor involvement of the pulmonary vessels. AB - A prospective morphological study of tumor involvement of the pulmonary vessels (TIPV) was undertaken on 203 consecutive autopsy cases of malignancies. The lungs were removed as a block and 15 sections (3 from each lobe) were analyzed. Site of origin, histological type and staging of the tumor, topographic distribution of the tumor emboli in the lungs, right ventricular hypertrophy and dilatation, pulmonary infarct, pulmonary vascular sclerosis and lung metastases were recorded in each case. TIPV was detected in 84 (41.4%) cases, the highest frequency reported until now. In 28 cases, TIPV was considered to be the main cause of death. The breast, liver, and pancreas were primary sites in more than 50% of the cases in which TIPV was observed. TIPV was more prevalent in epithelial neoplasms and showed a strong correlation with advanced disease. There was no significant difference among topographic regions of the lungs. The cases with TIPV were correlated with a high frequency of right ventricular hypertrophy and dilatation, vascular sclerosis and pulmonary metastases but not with pulmonary infarcts. PMID- 1437287 TI - Glomerulosclerosis and hyalinosis in rabbits. AB - Histological appearances of remnant kidney in female New Zealand white rabbits undergoing left nephrectomy at 6 mths were studied. All 20 rabbits had evidence of previous Encephalitozoon cuniculi (E. cuniculi) infection. Half of the 10 uninephrectomized and 10 control animals completed 3 pregnancies before sacrifice (15 mths). Twelve of 30 kidneys at sacrifice showed focal and segmental hyalinosis and sclerosis (FSHS), a lesion not previously reported in rabbits. Four of 5 kidneys in both uninephrectomized pregnant and uninephrectomized virgin animals showed FSHS compared with 2 of 10 in both control pregnant and non pregnant rabbits (p = 0.0026). More glomeruli were sclerosed in control pregnant (median 3.5%) than non pregnant animals (median 0.4%) (p < 0.005). Median right kidney weights per kilogram body weight were greater in previously nephrectomized animals (3.9 gm/kg) than controls (2.6 gm/kg), (p < 0.001). Absolute glomerular area was increased in hypertrophied kidneys, however, after correction for kidney weight, glomerular area was smaller in previously uninephrectomized animals than controls (p < 0.0001). PMID- 1437288 TI - Test and teach. Number 69. Diagnosis: Tubo-ovarian actinomycosis. PMID- 1437289 TI - Peanut agglutinin (lectin from Arachis hypogaea) binding to hemopoietic cells: an immunophenotypic study using a biotin streptavidin technique. AB - The lectin peanut agglutinin (PNA) was used to study the surface carbohydrate expression of galactose beta 1, 3, N-acetylgalactosamine by normal and malignant hemopoietic cells. Immunostaining was performed using biotinylated PNA and a streptavidin-alkaline phosphatase staining technique on 78 patients. The study was undertaken to enlarge on previous reports of lectin binding to cells of hemopoietic origin and to establish the potential role of biotinylated PNA as a component of an immunotoxin for in vitro purging of bone marrow in patients with multiple myeloma. In normals only monocytes, macrophages, centroblasts and plasma cells showed reactivity. Of the hematological malignancies, all cases of multiple myeloma were positive and non-Hodgkin's lymphoma cases with a large cell component had positive centroblasts. Two of 5 cases of acute myelomonocytic leukemia, one case of chronic myelomonocytic leukemia and one case of pleomorphic T cell non-Hodgkin's lymphoma showed PNA positive neoplastic cells. The reactivity of biotinylated PNA with centroblasts and plasma cells suggests that it may be of potential value when linked to a streptavidin-ricin conjugate in the in vitro purging of bone marrow of patients with multiple myeloma prior to autologous bone marrow transplantation. PMID- 1437290 TI - Heparin-induced thrombocytopenia: laboratory investigation and confirmation of diagnosis. AB - We report here on the usefulness of the 14C-serotonin release assay for the laboratory confirmation of the clinical diagnosis of heparin-induced thrombocytopenia syndrome (HITS). Over the past 3 yrs, some 140 individual serum samples have been tested in our laboratory for heparin-associated anti-platelet activity ('heparin antibodies'). These included sera from 54 selected (4 positive, 50 negative) controls and a group of 86 patients where the test was requested on clinical grounds. Of 20 patients derived from within our institution, 7 out of 8 patients (88%) with good clinical probability of HITS were confirmed to have heparin platelet antibodies by the serotonin release assay. In contrast, only 2 out of 9 patients (22%) with a low clinical probability of HITS were shown to be positive by this procedure, as were 2 out of 3 patients (66%) deemed to have an 'intermediate' clinical probability of HITS. In addition, screening of 50 serum samples forming a 'negative-control non-HITS' group (either patients on heparin therapy without thrombocytopenia, patients with non-heparin associated thrombocytopenia [eg. ITP*, other drug related], or normal laboratory volunteers), consistently failed to display heparin associated anti platelet activity by the 14C-serotonin release assay. In addition to the good specificity and sensitivity described above, the 14C-serotonin release assay was found to be nearly twice as sensitive when compared to the platelet aggregation procedure, and it is therefore a useful diagnostic test for the confirmation of clinically suspected HITS. PMID- 1437291 TI - Acceptance of class II major histocompatibility complex disparate skin grafts associated with suppressor cells and elevated Langerhans cell numbers. AB - Class II major histocompatibility complex (MHC) molecules are only present on Langerhans cells (LC) in normal murine epidermis. Depletion of this antigen with the chemical carcinogen dimethylbenzanthracene (DMBA) causes I-E disparate B10.A(2R) congenic tail skin to be accepted permanently when grafted onto B10.A(4R) recipients. Adoptive transfer of spleen cells from these recipients into naive syngeneic hosts inhibited the ability of the host mice to reject untreated B10.A(2R) tail skin grafts. Hence DMBA-treated LC depleted I-E disparate skin grafts activate suppressor cells which did not inhibit BALB/c mice from rejecting a B10.A(2R) tail skin graft. In contrast, the tobacco derived carcinogen benzo(a)pyrene (BP) increased the number of epidermal LC but had no effect on either class I or class II MHC disparate skin graft survival time. This confirms that the number of class II MHC-positive LC is critical for the initiation of skin graft rejection; when the threshold level is attained graft rejection proceeds at a maximal rate that cannot be enhanced by raising the number of LC. The tolerant skin grafts had increased numbers of LC; this was not observed in syngeneic grafts and therefore may be related to the active suppression of immunity. PMID- 1437292 TI - Development of trimethoprim-resistance in Salmonella typhi during therapy. AB - A typhoid patient was infected with a fully-sensitive, plasmidless strain of Salmonella typhi which acquired resistance to kanamycin, sulfamethoxazole and trimethoprim during cotrimoxazole therapy. The resistant post-treatment strain harboured 4 plasmids of 62, 4.1, 3.8 and 3.0 Md in size. Kanamycin-, sulfamethoxazole- and trimethoprim-resistance were borne on a transferable 62 Md plasmid which was compatible with groups FI, FIme, FII, FIV, H1, H2, B, I1, I2, J, K, M, N, T, X, W and P. Sulfamethoxazole-resistance was also borne on the 4.1 Md plasmid. The 3.8 Md plasmid was not transferable; the 3.0 Md plasmid was transferable but did not confer antibiotic resistance. Excluding the strain described here, only 5 out of 35 other S typhi isolates contained plasmids. This is the first report of trimethoprim-resistant S typhi in Hong Kong. PMID- 1437293 TI - Capnocytophaga canimorsus septicemia associated with cat scratch. AB - A case is reported of Capnocytophaga canimorsus (formerly CDC group DF-2) septicemia following cat scratch in a patient with congenital asplenia. The case is of interest in that (1) the clinical presentation provided no indication as to the cause of the patient's illness. (2) C. canimorsus infection following cat bite or scratch has been reported far less frequently than following dog bite. (3) The clinical course of the illness may have been modified by previous and concurrent warfarin therapy. PMID- 1437294 TI - Mycobacterium fortuitum endocarditis in a patient with chronic renal failure on hemodialysis. AB - A case of infective endocarditis due to M. fortuitum in a 54 yr old female with chronic renal failure on hemodialysis is presented. Clinical, microbiological and autopsy findings are discussed. PMID- 1437295 TI - Beta-lactamase induction by imipenem in Yersinia enterocolitica. AB - Five strains of Yersinia enterocolitica belonging to 5 different biotypes were induced to beta-lactamase production with imipenem in broth culture at 28 degrees C. Strains belonging to biotypes 1A, 1B, 2 and 3 showed a 26 to 73 fold increase in beta-lactamase activity after 180 min in the presence of 0.5 mg/L imipenem. Biotype 4 strain, by contrast, did not show obvious enhancement of its beta lactamase activity in the same experiments. Enzyme B in biotypes 1B, 2 and 3 and enzyme "B-like" in biotype 1A were shown to be responsible for the increase of the beta-lactamase activity, but neither enzyme nor any similar enzyme was found to be present in biotype 4 strain. PMID- 1437296 TI - Implications of rDNA technology in the microbiology laboratory. AB - The present and potential future roles in service and research microbiological laboratories of recombinant DNA (rDNA) techniques (nucleic acid hybridization, nucleic acid amplification, in situ hybridization, pulsed field gel electrophoresis) are described. Applications rDNA technology include the detection of micro-organisms; an approach to the understanding of their role in disease pathogenesis and provision of alternative strategies for studying the epidemiology of infectious diseases. PMID- 1437297 TI - Bizarre parosteal osteochondromatous proliferation of the hand in a young man. AB - We report a case of a solitary osteochondromatous tumor on the hand of a 38 yr old man. This had radiological and histological features distinct from an osteochondroma and demonstrated the features first described as bizarre parosteal osteochondromatous proliferation. These lesions have a tendency for local recurrence but no metastatic behaviour has yet been reported. We highlight 2 histological features which have not been previously described. PMID- 1437298 TI - Papillary carcinoma arising in ectopic thyroid tissue within a branchial cyst. AB - The first case of a papillary carcinoma arising in ectopic thyroid tissue within a branchial cyst in a 34 yr old woman is presented. This also adds to the existing list of unusual sites where ectopic thyroid tissue has been described. All histological types of carcinoma have been reported in ectopic thyroid tissue, papillary carcinoma being the most common histological type, accounting for 85% of these tumors. The criteria for establishing this diagnosis of carcinoma arising in ectopic thyroid tissue within branchial cyst is discussed. PMID- 1437300 TI - Mesocolonic lymphangioma: a case report with immunoperoxidase and electron microscopic studies. AB - A 14 yr old girl presented with a large cystic mass in the transverse mesocolon which was completely excised. Cystic lymphangioma was diagnosed, based on the specific histologic, immunoperoxidase and ultrastructural findings. PMID- 1437299 TI - Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin change (POEMS) syndrome with IgG kappa paraproteinemia. AB - The POEMS syndrome is an infrequently reported multisystem disorder which presents usually as an obscure polyneuropathy, with almost all cases reported in Japan. A 64 yr old caucasian man presented with a 12 mth history of a severe sensorimotor neuropathy in association with dermato-endocrine features. Detection of a monoclonal IgG kappa paraprotein and mixed osteosclerotic/lytic bone lesions consistent with a plasma cell dyscrasia led to diagnosis of the POEMS syndrome. Unique ultrastructural features were present on sural nerve biopsy in addition to the unusual association with monoclonal kappa-light chain. This case illustrates that the POEMS syndrome may also occur in caucasian subjects. PMID- 1437301 TI - Nephrotic syndrome associated with angiofollicular lymph node hyperplasia, and subsequent amyloidosis. PMID- 1437302 TI - Immunological assessment in the treatment of HIV infection. PMID- 1437303 TI - A case for revival. PMID- 1437304 TI - Ki67 immunohistochemical evaluation in colorectal cancer and normal colonic mucosa. Possible clinical applications. AB - Cell proliferation was evaluated by Ki67 monoclonal antibody in 33 colorectal adenocarcinomas and in the normal colonic mucosa. Immunoreactivity was assessed independently by two observers in two subsequent evaluations with a semiquantitative method, by counting at least 2000 cells in two distinct neoplastic specimens (central and peripheric section). There was an excellent intra-inter observer agreement in Ki67 score for each specimen. The tumor score range from 7 to 70% (median 48.8), without any significant correlation with sex and age of the patient and location, size, staging and grading of the neoplasm. Tumor Ki67 score was almost identical in central (46.96%) and in peripheral section (49.24%), and always higher than in normal mucosa. There was no distinction in Ki67 score in normal mucosa at various distances from the tumor. In our experience, Ki67 provides a reliable and reproducible method for assessment of proliferative activity; its clinical applications need further studies. PMID- 1437305 TI - [Prognostic value of cellular ploidy in adenocarcinoma of the middle rectum]. AB - A retrospective study of DNA content in 38 medium-rectal adenocarcinomas (a rectal part between 8 and 12 cm. from anus) was performed using flow cytometry in order to find probable correlations among ploidy, grading, staging and survival in patients who had undergone a surgical operation from January 1975 to December 1989. At the beginning of the work, 21 patients were alive and 17 were dead. Histologically 15 carcinomas (39.4%) were G1, 22 (57.8%) were G2 and only 1 (2.6%) was G3. Moreover 1 case (2.6%) was pT1, 7 (18.4%) were pT2 and 30 (78.9%) were pT3. 11 adenocarcinomas (29%) were euploid and 27 (71%) were aneuploid. These percentages agree with literature data. 11 of dead patients (64.7%) had aneuploid neoplasias and 6 (35.3%) diploid; 16 of alive patients (72.2%) had aneuploid carcinomas and 5 (23.8%) diploid. The difference of survival between aneuploid and diploid carcinomas isn't statistically significative (X2 = 0.168 ns). No correlation was found among aneuploidy, grading and staging, probably on account of small number of analyzed cases, owing to particular and little rectal part included in the study. Likely, having a larger case number we'll be able to obtain more incisive informations from this type of analysis in the next future. PMID- 1437307 TI - Morphology of non A-non B hepatitis (HNANB). A study of 104 cases. AB - A series of 104 liver biopsies from patients with clinical HNANB were classified under code into established histologic groups. Activity and basic features were semiquantitatively assessed using a score system. In 23/104 cases non viral lesions were diagnosed. After breaking the code the remaining 81 hepatic biopsies were ranged into three groups: post-transfusional cases (PT) (n. 20), sporadic cases with clinically documented initial "acute hepatitis" (SP1) (n. 44), sporadic cases without determined onset of disease (SP2) (n. 17). There were no statistically significant features discriminating histologically PT group from SP 1 + 2 group. However, aggressive forms of hepatitis (acute hepatitis with piecemeal necrosis [AVH+PMN] and chronic aggressive hepatitis [CAH]) were more frequent in PT group (11/20 = 55% in PT versus 28/61 = 45.9% in SP 1+2 groups). No statistical significant differences were detected for the scored basic pattern (i.e. acidophilic body type, mononucleosis-like bead file pattern, etc.). Bile duct lesions were observed approximately with the same frequency in PT and SP1 groups. Prevalence of fatty change was striking: 55% in PT group and 54.1% in SP1 group. PMID- 1437306 TI - [Chronic calculous cholecystitis: elementary and dysplastic lesions, echographic correlations and immunohistochemical approach]. AB - The morphological analysis of 223 cases of chronic calculous cholecystitis has drawn attention to the following outstanding facts: (a) elementary lesions are numerous (above all ulceration, mucosal erosion, antral and intestinal metaplasia) and put together a complex sight; (b) mild, moderate and severe dysplasias have a surprising high incidence (67%), even in the age-group under 40; (c) dysplasia is more common in the gallbladders bearing parallel hyperplastic and metaplastic mucosal changes, if compared with gallbladders where these changes are lacking; (d) thickness of gallbladder's wall and incidence of dysplasia are in direct relation; (e) echographic preoperative assessment of wall's thickness has predictive value for presence of dysplasia; (f) CEA and CA 19-9 have a progressively increasing expression in the various degrees of dysplasia. PMID- 1437308 TI - [Pheochromocytoma and catecholamine cardiomyopathy]. AB - We describe a 40 years old patient deceased of pheochromocytoma-caused heart failure, with no previous specific symptomatology. At autopsy the heart was characterised by thin cardiac walls and cavity dilatation. Histologic pattern showed extensive myocardial fibrosis and some acute myocytolytic areas. This pattern is equal to that of prolonged and decompensated stress cardiomyopathy. These pathologic pictures are both caused by catecholamines cardiotoxicity. PMID- 1437309 TI - Immunocytochemical detection of megakaryocytes by endothelial markers: a comparative study. AB - By endothelial markers such as FVIII, UEA-I, CD31 and QBEND/10, the Authors have investigated the immunohistochemical pattern of bone marrow megakaryocytes in myelodysplastic (8 cases) and myeloproliferative (35 cases) disorders as well as in control biopsies (8 cases). An evident cytoplasmic positivity with FVIII and UEA-I was encountered in all normal and pathological specimens, whereas the immunolocalization of CD31 was limited to megakaryocytes present in normal bone marrow biopsies or in cases of myelofibrosis. No immunostaining with QBEND/10 was observed in any case, although the most selective staining of endothelial cells of bone marrow vessels was noted with this antibody. The usefulness to utilize endothelial markers in order to identify atypical and immature forms of megakaryocytes as well as micromegakaryocytes, especially in myelofibrosis by the aid of CD31, was also discussed. PMID- 1437310 TI - [Chondrosarcoma of the hyoid bone. Follow-up and cytological study of a case]. AB - The follow-up study of one chondrosarcoma of the hyoid bone is reported; the tumor was a well differentiated grade II chondrosarcoma that relapsed after 10 months and metastasized after 6 years. Fine needle aspiration cytologic method was utilized for the diagnosis of the lung metastases. Cytologic criteria in the differential diagnosis of the chondrosarcoma are discussed. Follow-up of the extra-skeleton chondrosarcoma has to be continued for a long time independently from the grade of differentiation. PMID- 1437311 TI - The general pediatrician's role in managing asthma and allergies. PMID- 1437312 TI - A step-wise approach to the changing drug therapy of asthma. PMID- 1437313 TI - Smoking cessation for parents of children with asthma. PMID- 1437314 TI - Anaphylaxis in children. PMID- 1437315 TI - Risk factors for developing wheezing and asthma in childhood. AB - Wheezing lower respiratory tract illness in infancy and asthma share the clinical findings of wheezing and respiratory distress. Although the link between wheezing lower respiratory tract illness in infancy and the subsequent development of asthma is a limited one, both conditions do share some common risk factors, including exposure to environmental tobacco smoke, difficult living conditions (low socioeconomic class, crowding, allergen exposure), and increased risk in males. The impact of baseline lung function on wheezing lower respiratory tract illness risk is substantial and may be independent of airway reactivity. In contrast, the development of chronic airway inflammation mediated by allergic sensitization plays a central role in the development of persistent asthma. Although the endogenous risks for these two outcomes may be fixed, it is clear that caregivers may help to reduce or eliminate the exogenous risks listed earlier by parental education and improvement of the living conditions of young children. PMID- 1437316 TI - Asthma pathogenesis and the implications for therapy in children. AB - Gaining greater insight into the pathogenesis of asthma has redefined the approach to treatment of children with asthma. Clearly, the Expert Panel of the National Heart, Lung, and Blood Institute National Education Program has played a major role in taking the message to a wide audience of health care providers. Although only early trends are evident at this point in time, within several years therapeutic trends underway currently will be more commonplace, and we may observe how asthma continues to impact society and our health care system. The approach to therapy will continue to evolve and most likely be controversial for years to come. PMID- 1437317 TI - Crisis in asthma care. AB - Reports of increases in both hospitalizations and deaths due to asthma have provided a sense of crisis in asthma care. This article examines issues concerning this sense of crisis. The authors review current trends in prevalence, morbidity, hospitalization, and mortality from asthma and examine possible reasons for changes that have occurred. A review of data suggesting that asthma can result in irreversible, chronic airway obstruction is presented. Finally, the authors discuss the role of the primary care physician in the management of asthma. PMID- 1437318 TI - Pediatric pulmonary function testing in asthma. AB - Pulmonary function testing is an important tool in the management of asthma. Lung function can be readily assessed in both the office and patient's home. This article reviews spirometry, peak flow meters, and bronchial challenge testing. Their interpretation and clinical use are presented as well. PMID- 1437320 TI - Allergens and asthma. AB - This article presents the studies that show that asthma in children is strongly associated with sensitization to dust mite and other indoor allergens. In addition, the recent evidence that this association reflects a causal relationship between allergen exposure and asthma is reviewed. The relevance of quantitative measurements of the major indoor allergens (dust mite, cockroach, and cat) in the houses of children with asthma is discussed. Finally, the increasing evidence that avoidance measures can be an effective treatment for asthma is considered together with the details about avoidance protocol for dust mite and cat allergen. PMID- 1437319 TI - The impact of respiratory infections on asthma. AB - It is apparent that the effects of viral respiratory infections on the development of airway hyperresponsiveness are multiple and interrelated and involved the production of viral specific IgE, upregulation of leukocyte inflammatory activity, enhancement of the factors involved in the generation of late phase allergic responses, altered beta-adrenergic and cholinergic nervous system activity, and damage to the airway epithelium. The summation of these effects is the development of airway inflammation rather than a direct effect on bronchial smooth muscle, per se. An understanding of this pathogenesis underscores the relative importance of anti-inflammatory rather than antimicrobial therapy in viral-induced exacerbations in asthma symptoms. PMID- 1437321 TI - Management of acute asthma. AB - Patients with acute asthma experience increased airway obstruction, increased work of breathing, and ventilation-perfusion mismatch. Careful observation and assessment of the patient are fundamental for successful treatment. Therapy is dictated by the severity of the acute episode. Prevention of subsequent flares of asthma needs to be initiated as the patient convalesces. PMID- 1437322 TI - Complicating features of asthma. AB - The recognition of factors other than asthma that make asthma worse, are confused with asthma, or occur concurrently with asthma and may or may not interact with asthma is as important as dealing with the asthma itself. In this article I have tried to give an overview of some of these factors: what they are, how they affect patients with asthma, and what to do about them. The recognition of a covert chronic sinusitis, for example, is often key to controlling a person's disease when it appears that everything is being done appropriately. Close attention to these factors will increase the success of treatment of asthma and improve the quality of life of patients. PMID- 1437323 TI - Patient education. AB - Only recently has it been appreciated that the considerable morbidity of asthma can be reduced with tools readily available to every physician who treats children. The pharmacotherapeutic armamentarium has been strengthened by better understanding of the pathogenesis of asthma, the impact of inflammation, and the role of preventive therapy. The task remains to put this expanded knowledge to use to help a larger number of children with asthma and their families to diminish the impact that the disease has on their lives. Concomitant with increased understanding of the pathophysiology of asthma and the medications used to control the process has been a greater appreciation of the role of co management or self-management. Several programs have been developed to help parents and children with asthma gain better control over the disease, thus decreasing morbidity and significantly improving quality of life. These programs are available to physicians and health care organizations, and it is strongly recommended that asthma education, both as a formal course and in the physician's office, be regularly incorporated into the care plan for every child with asthma. PMID- 1437324 TI - Is asthma curable? AB - The information reviewed here supports the concept that asthma is potentially curable. Reports of complete, durable remission of asthma can no longer be regarded as fortuitous occurrences, unrepresentative of asthma in general. Systematic studies of anti-inflammatory drug therapy designed to explore possible induction or remission of asthma clearly are warranted. Studies of aggressive anti-inflammatory drug therapy of asthma at the onset, to avoid establishment of chronic asthma, also are desirable. The current goals of therapy of asthma have been revised to include reduction of airway hyperreactivity with topical anti inflammatory drugs, in addition to relief of current symptoms. This approach may provide valuable resistance to exacerbations in response to antigen exposures, infections, exercise, or irritants. Pathophysiologic mechanisms apparently essential to the establishment and perpetuation of chronic asthma have been identified. These processes may be vulnerable to eradication by combination therapy with existing pharmacologic agents such as cyclosporin A or FK-506 (to suppress cytokine production), gold, methotrexate, and other anti-inflammatory drugs, alone or in combination. Equally important, the vigorous anti-inflammatory therapy may be necessary only long enough to achieve a resolution of the chronic pulmonary inflammation. Systematic studies of the use of these agents to induce partial, or complete, stable remissions of asthma should be performed. In the past, remissions of asthma in children with neoplasia and the other patients presented herein were complete, durable, and welcome, but they were largely unexpected and unpredictable. For the future, there is increasing reason to believe that predictable pharmacologically induced remission of asthma will be feasible. PMID- 1437325 TI - Branhamella catarrhalis colonization in preschool asthmatics. AB - Branhamella catarrhalis has been associated with exacerbations of chronic bronchitis and asthma in adults. To investigate the possible role of B. catarrhalis in asthma of early childhood, we took posterior pharyngeal swabs from 24 normal children, 20 well asthmatics, and 20 acutely wheezy asthmatics, all between 1 and 4 years of age. On culture, 33% of the normal children were colonized with B. catarrhalis; colonization rates in the well asthmatics (70%) and in the wheezy asthmatics (75%) were significantly higher than in normals. The nature of this association requires further study. PMID- 1437326 TI - Spontaneous desaturations in intubated very low birth weight infants with acute and chronic lung disease. AB - Patients with chronic lung disease (CLD) have frequent episodes of spontaneous desaturations. Utilizing computerized pulse oximetry (CPO) we quantified the frequency and severity of spontaneous desaturations in very low birth weight (VLBW) infants with CLD. Thirty-four studies by CPO were performed in intubated infants for 4 hours; 17 patients (birth weight, 550-980 g; postnatal age 28-85 days) had CLD, and 17 (birth weight, 520-980 g; postnatal age, 1-7 days) had acute lung disease. Oxygen saturation (SaO2) was measured with the Nellcor N-200 oximeter, its serial output (updated once a second) captured by a computer. Pulse rate, pulse amplitude, and heart rate were also monitored continuously. We measured respiratory system mechanics in 23 patients. Tidal volume (VT), respiratory system compliance (Crs), and resistance (Rrs) were obtained by the PeDS system. Spontaneous desaturation to SaO2 less than 90% occurred for 4.5% of the time in acute patients vs. 27.1% of the time in chronic patients (P less than 0.0001); to SaO2 less than 85%, 0.7% vs. 7.6% of the time in acute vs. chronic patients (P less than 0.002); and to SaO2 less than 80%, 0.4% vs. 2.6% of the time in acute vs. CLD patients (P less than 0.05). Rrs was significantly higher in the ventilated patients with CLD (174 cmH2O/L/s) than in the ventilated patients with acute lung disease (94 cmH2O/L/s, P less than 0.0001). The mean Crs values of the two groups were comparable. Our preliminary data indicate that VLBW infants with CLD receiving assisted ventilation have a greater number of spontaneous desaturation episodes, as compared to patients with acute lung disease. PMID- 1437327 TI - Intensive care course and outcome of patients infected with respiratory syncytial virus. AB - PICU admissions of 97 children positive for respiratory syncytial virus on fluorescent antibody screening were reviewed; 68% of 44 patients without history of preceding disease (Group I) and 79% of 53 patients with preceding pulmonary, cardiac, or other disease (Group II) required ventilation. In Group I ventilated children weighted significantly less (P = 0.001) and were of lower chronological (P = 0.02) and post-conceptional ages (P = 0.02) than those not ventilated. Eighteen infants ventilated for apnea weighted significantly less (P = 0.003), were more often born at less than or equal to 37 weeks gestation (P = 0.001) and were at lower post-conceptional age than 11 infants ventilated for progressive respiratory deterioration. There was no significant difference in mean weight, chronological age, post-conceptional age, CO2, or pH between 12 admissions with BPD who required ventilation for RSV infection and 5 who did not require ventilation. Ribavirin administration to five ventilated patients with BPD did not significantly alter the duration of intubation of PICU stay. Six patients with cardiac disease required longer periods of ventilation than others (Group I, P = 0.001; all others in Group II, P = 0.04). No deaths occurred in Group I, while 6 of 53 (11%) patients in Group II died. In this series immuno compromise placed patients at greatest risk of dying. Mechanical ventilation can be safely managed in previously healthy, RSV infected infants and should be initiated before significant cardiorespiratory compromise arises. PMID- 1437328 TI - Prolonged apnea and oxyhemoglobin desaturation in asymptomatic premature infants. AB - Seventy-eight longitudinal four-channel recordings of heart rate, thoracic impedance, nasal thermistry, and pulse oximetry were performed on 26 asymptomatic premature infants (gestational age, 29.9 +/- 1.58 weeks; birth weight, 1,753 +/- 226 grams; postconceptional age, 34.3 +/- 2.0 weeks; postnatal age, 4.41 +/- 2.40 weeks; all values mean +/- SD). Tracings were scored for central and obstructive apnea, bradycardia, periodic breathing, apnea density, and prolonged apnea. The studies demonstrated 585 episodes (7.41/recording) of oxyhemoglobin desaturation with less than 90%. Recordings had a mean of 16.1 episodes of central apnea, 3.04 episodes of obstructive apnea, and 2.34 episodes of bradycardia. Periodic breathing and short obstructive apneas correlated significantly with the total number of oxyhemoglobin desaturations of less than 80% and 90%. Episodes of prolonged apnea were seen in 20 of 78 recordings. In the latter a significantly higher number of total desaturations (less than 90%), desaturations less than 80% and 90% in association with apnea and with bradycardia, longer desaturations, desaturations during sleep, and isolated bradycardia were observed. Variations in heart rate, thoracic impedance, nasal air flow, and pulse oximetry are associated with episodes of oxyhemoglobin desaturation in asymptomatic premature infants. These infants, although asymptomatic, may be at risk for impaired tissue oxygenation. PMID- 1437329 TI - Gas exchange during exercise in diabetic children. AB - The purpose of this study was to evaluate the cardiorespiratory and metabolic response to exercise in 33 children, aged 9 to 15 years, affected by type I diabetes mellitus, in comparison with 47 age-, sex-, weight-, and height-matched healthy children. All diabetic children were on a mixed split-dose insulin regimen, consisting of both regular and long-acting insulin in the morning and evening. The last insulin injection was administered on average 6 hours before the test. The mean duration of diabetes mellitus was 5.0 +/- 3.1 years. The metabolic control was evaluated on the basis of HbA1 levels (mean, 8.9 +/- 1.8%). Pulmonary function tests and progressive exercise tests on the treadmill were performed. Gas exchange, ventilation, and heart rate (HR) were monitored during the tests. The O2 pulse (VO2/HR) was calculated. There was no difference in the baseline oxygen uptake (VO2) between the diabetic children and the control group. VO2 peak was significantly lower (P less than 0.01) in the diabetic adolescents (41.2 +/- 5.9 mL/min/kg) compared to control subjects (46.3 +/- 9.6 mL/min/kg) and it was achieved at an earlier (P less than 0.01) time of run (7.5 +/- 1.8 vs. 9.1 +/- 2.8 min). Anaerobic threshold and minute ventilation were similar in the two groups. The O2 pulse throughout the test was significantly lower (ANOVA, P less than 0.001) in the diabetic group compared to the controls. No differences were found in resting and post-exercise spirometric values. In conclusion, our study shows that well-controlled diabetic adolescents have a reduced working capacity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437330 TI - Evaluation of the multiple linear regression method to monitor respiratory mechanics in ventilated neonates and young children. AB - A potentially useful method to monitor respiratory mechanics in artificially ventilated patients consists of analyzing the relationship between tracheal pressure (P), lung volume (V), and gas flow (V) by multiple linear regression (MLR) using a suitable model. Contrary to other methods, it does not require any particular flow waveform and, therefore, may be used with any ventilator. This approach was evaluated in three neonates and seven young children admitted into an intensive care unit for respiratory disorders of various etiologies. P and V were measured and digitized at a sampling rate of 40 Hz for periods of 20-48 s. After correction of P for the non-linear resistance of the endotracheal tube, the data were first analyzed with the usual linear monoalveolar model: P = PO + E.V + R.V where E and R are total respiratory elastance and resistance, and PO is the static recoil pressure at end-expiration. A good fit of the model to the data was seen in five of ten children. PO, E, and R were reproducible within cycles, and consistent with the patient's age and condition; the data obtained with two ventilatory modes were highly correlated. In the five instances in which the simple model did not fit the data well, they were reanalyzed with more sophisticated models allowing for mechanical non-homogeneity or for non-linearity of R or E. While several models substantially improved the fit, physiologically meaningful results were only obtained when R was allowed to change with lung volume. We conclude that the MLR method is adequate to monitor respiratory mechanics, even when the usual model is inadequate. PMID- 1437331 TI - Apnea and periodic breathing in healthy full-term infants, 12-18 months of age. AB - Many children older than 12 months of age are now on home monitors. Home pneumograms performed on normal infants have established standards, and have been used to evaluate infants during their first year. However, no standards have been described for infants older than 12 months. We, therefore, recorded the standard pneumogram on 88 full-term healthy infants who were 12-18 months of age. We analyzed the recordings for average respiratory and heart rates, apnea (greater than or equal to 6 seconds) density, longest apnea, periodic breathing, and bradycardia for 12 hours. We compared the values in males vs. females and in infants 12-14.9 months vs. 15.0-18.0 months of age. Since there was no difference in any parameter measured in any group, we combined the values to determine the normal values for this population. PMID- 1437332 TI - Delivery of micronized budesonide suspension by metered dose inhaler and jet nebulizer into a neonatal ventilator circuit. AB - We compared the delivery of a micronized suspension of budesonide by a metered dose inhaler (MDI) with two different spacers (Aerochamber and Aerovent) and by two jet nebulizers (MAD2 and Ultravent) to a ventilated neonatal test-lung using a standard neonatal ventilator circuit. The combination of MDI and Aerochamber was significantly better at delivering budesonide to a filter in front of the test lung (14.2% of aerosolized dose) than were either the MDI and Aerovent (3.6%) or the Ultravent or MAD2 jet nebulizers (0.02% and 0.68% of initial reservoir dose). Of the droplets emerging from the MDI, Aerochamber, and ET tube, 18% of the initial dose was in droplets less than 4.7 microns. Assuming that the test-lung model accurately reflects in vivo deposition, the combination of MDI and Aerochamber appears to be an extremely effective way of delivering budesonide aerosol to ventilated newborn infants. PMID- 1437333 TI - Long-term prednisone and azathioprine treatment of a patient with idiopathic pulmonary hemosiderosis. PMID- 1437334 TI - Diaphragmatic hypoplasia in association with hypoplastic lungs. PMID- 1437335 TI - Lipoid pneumonia in association with gastroesophageal reflux. PMID- 1437336 TI - On exogenous surfactant therapy. PMID- 1437337 TI - Lung mechanics and gas exchange in ventilated preterm infants during treatment of hyaline membrane disease with multiple doses of artificial surfactant (Exosurf) AB - Eight premature infants ventilated for hyaline membrane disease and enrolled in the OSIRIS surfactant trial were studied. Lung mechanics, gas exchange [PaCO2, arterial/alveolar PO2 ratio (a/A ratio)], and ventilator settings were determined 20 minutes before and 20 minutes after the end of Exosurf instillation, and subsequently at 12-24 hour intervals. Respiratory system compliance (Crs) and resistance (Rrs) were measured by means of the single breath occlusion method. After surfactant instillation there were no significant immediate changes in PaCO2 (36 vs. 37 mmHg), a/A ratio (0.23 vs. 0.20), Crs (0.32 vs. 0.31 mL/cm H2O/kg), and Rrs (0.11 vs. 0.16 cmH2O/mL/s) (pooled data of 18 measurement pairs). During the clinical course, mean a/A ratio improved significantly each time from 0.17 (time 0) to 0.29 (time 12-13 hours), to 0.39 (time 24-36 hours) and to 0.60 (time 48-61 hours), although mean airway pressure was reduced substantially. Mean Crs increased significantly from 0.28 mL/cmH2O/kg (time 0) to 0.38 (time 12-13 hours), to 0.37 (time 24-38 hours), and to 0.52 (time 48-61 hours), whereas mean Rrs increased from 0.10 cm H2O/mL/s (time 0) to 0.11 (time 12-13 hours), to 0.13 (time 24-36 hours) and to (time 48-61 hours) with no overall significance. A highly significant correlation was found between Crs and a/A ratio (r = 0.698, P less than 0.001). We conclude that Exosurf does not induce immediate changes in oxygenation as does the instillation of (modified) natural surfactant preparations. However, after 12 and 24 hours of treatment oxygenation and Crs improve significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437338 TI - Exosurf treatment investigational new drug phase: effect of an individualized third dose in infants with respiratory distress syndrome. AB - Of 95 infants treated with the synthetic surfactant, Exosurf, under a Treatment Investigational New Drug protocol, 17 received one dose, 40 received two, and 38 received three doses. Seventy-six (80%) of the infants were treated by rescue protocol. We retrospectively reviewed the clinical course of the 67 surviving rescue infants. We found that, compared to one- and two-dose infants, those treated with three doses of Exosurf were more premature, smaller, required a longer ventilator course, and had more frequent complications, including patent ductus arteriosus (PDA), intraventricular hemorrhage, nosocomial pneumonia, and apnea. They required higher oxygen concentrations starting 8 hr after their first dose and higher mean airway pressure (MAP) from the time of their second dose. These trends continued during all subsequent time points, as compared to infants treated with two doses. The third dose was administered an average of 17 hr after the second, resulting in little change of MAP, but some reduction in oxygen requirements. By 24 hr after the last dose, only 4% of three-dose infants were extubated compared with 30% of the two-dose and 71% of one-dose infants. In conclusion, repeated administration of Exosurf is not equally effective in every treated infant with respiratory distress syndrome (RDS) and complications of prematurity may affect or accompany poor response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437339 TI - Spirometric and endoscopic evaluation of airway collapse in infants with bronchopulmonary dysplasia. AB - We evaluated eight infants with bronchopulmonary dysplasia (BPD) at ages from 2 to 13 months who had repeated episodes of clinical respiratory deterioration associated with agitation. These episodes limited further weaning from ventilation or necessitated recurrent intubation and reinstitution of ventilation. All infants underwent spirometric evaluation and six also had endoscopic examination during simulated agitation episodes (elicited by toe pinching). All babies were found to have a very prolonged near zero expiratory airflow pattern, accompanied by vigorous diaphragmatic and abdominal muscle activity and rapid development of hypoxia. Six patients had endoscopically documented tracheal collapse under the same simulated circumstances. The episodes ceased with calming or sedation of the infants. PMID- 1437340 TI - The in vitro effect of triamcinolone acetonide on branching morphogenesis in the fetal rat lung. AB - We have studied the effect of triamcinolone acetonide (TAC) on airway morphogenesis of the Sprague-Dawley fetal rat in whole organ lung cultures from day 15 to day 21 of equivalent gestational age (6 days in culture). TAC produced an increased number of peripheral buds from day 18 onward and the airway and airspaces had larger lumens. Airway branching was increased compared to controls, and there was a higher proportion of airway epithelium and a lower proportion of mesenchyme. Cell height was significantly lower in TAC treated lungs except on day 17. This was due to accumulation of glycogen prior to the increased branching activity. In both controls and TAC-treated lungs, peripheral bud number and volume proportion of epithelium increased with time in culture, whereas volume proportion of mesenchyme, mean chord length of airways and airspaces, and epithelial cell height decreased. These changes were more pronounced in the TAC treated group and were significant. However, TAC-treated lungs were morphologically irregular. We conclude that TAC has a direct effect on airway morphogenesis and it promotes growth of morphologically abnormal lungs. TAC also appears to enhance airway branching and morphologic changes interpreted as increased epithelial maturation. PMID- 1437341 TI - A prospective trial using salivary-theophylline levels to guide asthma therapy. AB - In three prospectively designed studies, first saliva (SA) samples were collected simultaneously with serum (SE) from 86 children who received slow-release theophylline (Th) b.i.d. for treatment of bronchial asthma. SA was collected with a standardized sampling procedure. Regression analysis revealed a close correlation between SE and SA-Th levels (r = 0.959; SE = 1.87 x SA + 0.05) and yielded a "therapeutic SA-Th range" of 5.8 to 10.7 mg/L. In 16 children the diurnal variation was then assessed by measuring 6 SA-Th levels within 24 hr, using the same sampling method. At 0, 9, and 24 hr SE-Th levels were also measured. The levels of SE-Th and SA-Th were again closely correlated (0.914 less than or equal to r less than or equal to 0.949) and both remained constant over the 24-hr period. In the third prospective trial only SA levels were used to monitor Th therapy in 50 asthmatic children. Seven days after starting therapy SA Th levels were measured and then the Th dose was increased weekly until SA-Th levels above 5.8 mg/L were reached. The following day SE and SA samples were collected simultaneously and their Th levels compared. In 36 of the 47 children who completed the study therapeutic SE-Th levels (greater than or equal to 10 and less than or equal to 20 mg/L) were measured; in one patient it was greater than or equal to 20 mg/L, in 6 it was between 8.0 and 10 mg/L, and only 4 had SE levels less than 8.0 mg/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437342 TI - Early treatment of respiratory distress syndrome with bovine surfactant in very preterm infants: a multicenter controlled clinical trial. AB - OBJECTIVE: To determine the effect of bovine surfactant (SF-RI 1, Alveofact) administered during the first hour following birth to very premature infants [gestational age (GA), 25-30 weeks] in a multicenter, controlled trial. HYPOTHESIS: Survival without bronchopulmonary dysplasia (BPD; definition: ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration) at day 28 is increased in surfactant-treated infants (sequential analysis). PATIENTS AND METHODS: Thirty-four infants [GA 28.0 +/- 1.5 SD weeks, birth weight (BW), 1,048 +/- 299 g] received 50 mg/kg BW surfactant, whereas 35 infants (GA, 27.6 +/ 1.5 weeks, BW 969 +/- 269 g) served as controls. Retreatment with surfactant (up to three identical doses) 12-24 hours after the previous dose was permitted if FiO2 was greater than 0.5. RESULTS: Survival without BPD was significantly higher in surfactant treated infants (26/34) compared to controls (14/35; P = 0.003), but in the incidence of pulmonary air leaks, patent ductus arteriosus, intracranial hemorrhage, and nosocomial infections they were not different. CONCLUSION: Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome (RDS). PMID- 1437343 TI - IgG subclass antibody responses to alginate from Pseudomonas aeruginosa in patients with cystic fibrosis and chronic P. aeruginosa infection. AB - Chronic bronchopulmonary infection with alginate-producing, mucoid Pseudomonas aeruginosa is characteristically associated with cystic fibrosis (CF). A significant correlation between the antibody response to alginate and poor lung function has been reported. Enzyme-linked immunosorbent assays were developed for the quantitation of human IgG1, IgG2, IgG3, and IgG4 antibodies to P. aeruginosa alginate. We investigated the pattern of IgG subclass antibodies against P. aeruginosa alginate in serum of patients with CF, others with chronic P. aeruginosa infection, and healthy controls. Healthy controls and patients with CF, before they acquired P. aeruginosa infection, had no or very low titers of antibodies against P. aeruginosa alginate. The latter with chronic infection had significantly higher antibody levels than all others groups, including patients with chronic P. aeruginosa infection but no CF. CF with chronic P. aeruginosa infection led to an inverse correlation between lung function parameters and levels of IgG3 and IgG4. Fifty-seven patients with CF have been followed for an average of 12 years with multiple antibody assays covering the preinfection, early, and late stage of chronic infection. All of them developed IgG1 and IgG3 antibodies to alginate at the start of infection. IgG2 antibodies developed later and showed only a slow increase during the chronic infection. Patients who died had significantly higher IgG2 anti-alginate antibody levels than other investigated groups. Elevated levels of IgG2 and IgG3 antibodies to P. aeruginosa alginate are a sign of poor prognosis in CF. PMID- 1437344 TI - Response to inhaled bronchodilators and nonspecific airway hyperreactivity in children with cystic fibrosis. AB - We tested the hypothesis that children with CF who have a significant response to bronchodilator (BD) would respond positively to standard methacholine (Mch) challenge. Our objective was to correlate the response to BD with the concentration that produced a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1). We studied 22 patients (12 males), aged 10.5 +/- 0.7 years (mean +/- SE), with a Shwachman-Kulczycki score 82 +/- 2.6 and baseline FEV1 of 80 +/- 4.5% predicted. Baseline expiratory flows, static lung volumes, and airway resistance were measured before and 30 min after inhaled salbutamol. On a separate day, within 2 weeks, a Mch challenge was given, with doubling concentrations from 0.03 to 8.0 mg/mL. A positive challenge was defined as a PC20 less than or equal to 2.0 mg/mL, and a positive response to BD as a greater than 6% of FEV1 increase. Mch challenge yielded 17 responders (R) with a PC20 of 0.5 +/- 0.1 mg/mL, and 5 nonresponders (NR) with a PC20 of 8.8 +/- 2.9 mg/mL. Baseline FEV1 was 77 +/- 5.3% predicted in R compared to 89 +/- 6.3% in NR (P = less than 0.001). History of springtime rhinitis was positive in 9/17 R and 2/5 NR. No significant correlation was found between baseline FEV1 and PC20, or between change in FEV1 post-BD and PC20. A greater than 6% increase in FEV1 was seen in 14/17 R (83% sensitivity) and in none of the 5 NR (100% specificity). In R, 8/17 patients had baseline FEV1 less than 80% predicted, compared to 1/5 in NR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437345 TI - Soluble interleukin-2 receptor levels in infants with bronchopulmonary dysplasia. AB - Soluble interleukin-2 receptors (sIL2R) in plasma have been identified as a marker of lymphocyte activation. Lymphocyte activation as a manifestation of inflammation may be important in the pathogenesis of bronchopulmonary dysplasia (BPD). To test the hypothesis that infants with BPD have higher sIL2R levels, 12 infants with or at risk of developing BPD (GA +/- SD, 27 +/- 5 weeks; BW +/- SD 1,053 +/- 733 g) had plasma sIL2R levels determined and were compared to 20 infants being ventilated for respiratory distress syndrome (RDS) (GA +/- SD, 28 +/- 3.5 weeks; BW +/- SD, 1,133 +/- 390 g: P = NS for both GA and BW, t test). Tracheal aspirates in both groups were also analyzed for sIL2R levels. To control for the effects of postnatal age (PNA) and study weight (SW) on the sIL2R levels, another group of 16 nonventilated babies (NVB) had plasma analyzed for sIL2R (PNA +/- SD: 39 +/- 40 days NVB vs. 48 +/- 36 days BPD; P = NS); (SW +/- SD: 1391 +/- 250 g NVB vs. 1212 +/- 700 g BPD; P = NS). The following data were obtained for the plasma sIL2R levels (mean +/- SEM U/mL): RDS controls, 1,231 +/- 80; BPD infants, 1,790 +/- 120; NVB controls, 1,319 +/- 76; P = 0.0005 RDS vs. BPD and P = 0.002 BPD vs. NVB. There was no significant difference in the sIL2R levels for the infants at risk of developing BPD vs. the infants with established BPD. Also, when analyzed separately, infants at risk of BPD and the infants with established BPD had higher sIL2R levels than the RDS and NVB controls. No differences were noted in the tracheal sIL2R levels in the BPD vs. RDS groups. These data indicate that infants with BPD had significantly higher sIL2R levels in plasma than either RDS or NVB controls. Therefore, lymphocyte activation may play a role in the pathogenesis of BPD. PMID- 1437346 TI - On nebulized intranasal glucocorticoids. PMID- 1437347 TI - Liquid ventilation. PMID- 1437348 TI - Adaptive control of inspired oxygen delivery to the neonate. AB - Adaptive adjustment of inspired oxygen (FIO2), based on a desired percent arterial hemoglobin saturation (SO2) was achieved by on-line bedside control of the oxygen concentration delivered to the neonate. Fourteen infants with bronchopulmonary dysplasia (BW, 860 +/- 80 g; GA, 26 +/- 1 weeks; study age, 41 +/- 8 days) receiving oxygen-air mixtures by hood were studied. The desired range of SO2 from 92 to 96% with a target value of 95% was determined by pulse oximetry and maintained with adjustment of FIO2 using three modes: 1) standard neonatal intensive care protocol with oxygen delivery evaluated at 20 minutes intervals; 2) bedside manual control with FIO2 manipulation every 2 to 5 minutes; and 3) adaptive control with on-line adjustment of FIO2 according to a specifically designed adaptive program. Each study period was of 40 minute duration. SO2 values within a steady 94 to 96% range was achieved for 54% of the time with standard protocol, compared to 69% (P less than 0.01) with bedside manual control and 81% (P less than 0.01) with adaptive control. In addition, fluctuations in SO2 values and overshoots were less apparent with adaptive control of oxygen delivery. These data describe adaptive FIO2 control as an efficient alternative technique for achieving a stable desired range of oxygenation in neonates. PMID- 1437349 TI - Respiratory compliance in infants--a preliminary evaluation of the multiple interrupter technique. AB - Measurements of total respiratory system compliance (Crs) using the multiple occlusion technique (MOT) in spontaneously breathing infants can be difficult to interpret in the presence of an unstable end-expiratory level. Similarly, measurements using the passive flow volume technique (PFV) are invalidated if there is alinearity of the expiratory time constant (Trs), irrespective of respiratory effort. For possibly overcoming these problems, we assessed the feasibility of a technique using multiple interruptions of of a single expiration (MIT), obtaining several pairs of volume-pressure data, from one expiration, which relate to a single end-expiratory level. Crs was measured in 16 infants aged 0.5 to 20 months using the MOT, MIT, and PFV technique. The MOT and the MIT each failed in one (different) infant, both succeeding where the other failed. The PFV technique failed in five infants in whom no acceptable plateau of airway pressure during occlusion and no Trs could be obtained from a single breath. Failure to obtain a linear Trs was accompanied by failure of the MIT in only one infant. Individual differences between the MIT and the MOT were less than 9%. However, the PFV measurements varied from -16.3% and +25.7% of the values from MIT or MOT. The greatest differences between Crs values coincided with the greatest differences between volume intercepts of the extrapolated volume pressure (MOT, MIT) and flow-volume (PFV) data. From this preliminary study, the MIT proved as successful as the MOT, requiring fewer occluded breaths to measure Crs. In infants with a rapid respiratory rate, the data from several expirations can be merged and analyzed as for the MOT. PMID- 1437350 TI - Generalized lymphangiomatosis and chylothorax in the pediatric age group. AB - Four patients with generalized lymphangiomatosis presenting with chylothoraces are described. All four had bone involvement, two had involvement of the spleen, and one of the pericardium. The diagnosis was confirmed by typical radiology, histology, and in three patients by immunohistochemistry. Treatment was mainly palliative. Three patients died within 1/2 to three years of presentation. PMID- 1437351 TI - Pulmonary hyperplasia in Fraser syndrome. PMID- 1437352 TI - Diagnostic criteria for obstructive sleep apnea syndrome in children. PMID- 1437353 TI - Transcutaneous blood gas monitoring during salbutamol inhalations in young children with acute asthmatic symptoms. AB - The effect of salbutamol inhalations on transcutaneous blood gases was investigated in 23 children (aged 11 months-2.5 years) with asthmatic symptoms. After one salbutamol inhalation there was a mean increase in transcutaneous PO2 (tcPO2) of 0.5 kPa (P less than 0.01); after a second dose given 30 minutes later, the mean increase was 1.2 kPa (P less than 0.001). The increase in tcPO2 after only one dose of salbutamol was significantly correlated to age (P less than 0.01). No such correlation was observed after a second dose. The overall increase in tcPO2 after two salbutamol inhalations showed a negative correlation to the duration of the current symptomatic period (P less than 0.05). We conclude that salbutamol inhalations have beneficial effects in young children with acute asthmatic symptoms, even below the age of 18 months, provided that an adequate dose reaches the lung and preferably at an early stage of obstruction. PMID- 1437354 TI - Transcutaneous and arterial blood gas monitoring during acute asthmatic symptoms in older children. AB - The relationship between transcutaneous and arterial blood gases was investigated in 14 children with asthmatic symptoms, aged 7-15 years, before and after the inhalation of salbutamol. The degree of bronchial obstruction was assessed by forced expiratory volume in one second (FEV1) and maximum expiratory flow when 25% of FVC remained to be expelled (MEF25). On average the transcutaneous PO2 (tcPO2) was 1.3 kPa (range, 2.6-0 kPa) lower and the transcutaneous PCO2 was 0.6 kPa (range, 0-1.5 kPa) higher than the corresponding arterial values (P less than 0.01). The difference between arterial and transcutaneous PO2 was the same over the whole range of values studied (7.5-14 kPa). After the inhalation of salbutamol, the relationship between transcutaneous and arterial blood gases was not significantly changed. Changes in transcutaneous PO2 correlated to changes in MEF25 (P less than 0.05), indicating a common denominator, probably the conditions in the peripheral airways. We conclude that the close relationship between transcutaneous and arterial blood gases, even after the inhalation of a beta-2 agonist, indicates that the transcutaneous technique can be used for monitoring acute bronchial obstruction and for evaluating the effects of treatment in children of different ages. PMID- 1437355 TI - Intratracheal administration of pulmonary vasodilator agents. AB - We compared intravenous and intratracheal administration of histamine (0.4 and 1.6 micrograms/kg, respectively) and nitroglycerin (5.0 and 20.0 micrograms/kg, respectively) in seven hypoxemic 2 week old lambs, during right lung only perfusion, to see if intratracheal administration could limit their vasodilator action to the pulmonary vessels. The hemodynamic variables: pulmonary artery pressure (Ppa), left atrial pressure (Pla), pulmonary blood flow per kilogram (Q/kg), and aortic pressure (Pao) were measured at baseline and in each experimental state, then pulmonary vascular resistance (PVR) and systemic vascular input resistance (SVR) were determined. We found that intravenous histamine showed some pulmonary vasodilator selectivity in that it caused a 19% decrease of Ppa from baseline (P less than 0.002), a 23% decrease of PVR from baseline (P less than 0.002), and an 8% decrease of SVR from baseline (P less than 0.05). Intratracheal histamine produced smaller effects, decreasing Ppa by 11% from baseline (P less than 0.02), and PVR by 14% from baseline (P less than 0.02), while SVR was unaffected. Intravenous nitroglycerin decreased cardiac output by 16% from baseline (P less than 0.02), and also decreased SVR by 8% while producing a small increase in PVR. Intratracheal nitroglycerin caused a similar 17% (P less than 0.01) decrease in cardiac output, and again an increased PVR but a decreased SVR. This study confirms that histamine has some intrinsic pulmonary vasodilator selectivity. Furthermore, the data suggest that intratracheal administration may accentuate pulmonary selectivity by lessening systemic effects. Nitroglycerin, on the other hand, had untoward hemodynamic effects in the presence of hypoxia. PMID- 1437356 TI - The relationship of nasal disorders to lower respiratory tract symptoms and illness in a random sample of children. AB - We examined the relationship of nasal disorders, defined as frequent colds and sinus trouble, to lower respiratory tract symptoms in a random population of 718 children aged 4 to 11 years in East Boston, Massachusetts. Frequent colds were significantly associated with maternal smoking (odds ratio (OR) = 3.00; 95% confidence interval (CI) = 1.97, 4.58), and so was sinus trouble (OR = 4.73; 95% CI = 1.78, 12.51). After adjustment for maternal smoking, age and sex, frequent colds (OR = 2.88; 95% CI = 1.87, 4.42) and sinus trouble (OR = 4.95, 95% CI = 1.83, 13.39) remained significant predictors of lower respiratory tract symptoms in separate logistic regressions. If one restricted the cohort to the 513 children who also had personal smoking information and adjusted for this variable as well, the results for colds were unchanged (OR = 2.94; 95% CI = 1.78, 4.84) but the results for sinus trouble were now not statistically significant (OR = 2.30, 95% CI = 0.67, 7.94). We conclude that nasal disorders are associated with lower respiratory tract symptoms in children. PMID- 1437357 TI - Collagen degradation during postnatal lung growth in rats. AB - Postnatal lung growth involves remodeling of the structure seen at birth as new alveoli are formed. To determine the role of collagen degradation in this process, in particular of the basement membrane component, we studied the synthesis of total collagen and the degradation of collagen types I or IV in a series of rats from birth to 29 days of age. During the period of rapid cell proliferation to day 11, the collagen level per mg lung did not change though the rate of synthesis increased. Up to 40% of new collagen was rapidly degraded. At the end of the growth phase, the interstitium became thinner and less cellular. Collagen synthesis slowly decreased as the total collagen content increased in the lung, and less than 20% of newly synthesized collagen was degraded. Type I collagenase activity was highest during the cell proliferation phase, though less than 20% was due to active enzyme. In contrast, type IV collagen breakdown, also maximal in the first 11 days, was almost all due to enzymes present in the active form. The results demonstrate that rapid degradation of collagen, particularly the type IV form present in basement membranes, occurs during the early phase of postnatal lung growth. PMID- 1437358 TI - Ovarian cysts in the fetus and neonate--changes in sonographic pattern in the follow-up and their management. AB - In a multicenter trial we retrospectively evaluated the clinical and sonographic data of 49 neonatal ovarian cysts, 44 of which were detected prenatally and 5 on the first day after delivery. Of the 44 prenatally detected cysts 39 were purely cystic, 5 echogenic or had a mixed pattern. In 20 patients the cystic appearance changed during delivery from purely cystic to a mixed pattern being independent on the size of the cyst. 26 of the 44 cysts were treated surgically. Salpingotorsion was found in 8 and was independent on the size of the cyst. In 15 a salpingo-oophorectomy or oophorectomy was performed, in 11 the ovary was saved. 23 patients were followed sonographically: 15 cysts showed complete resolution within 14 months without correlation to the sonographic pattern. The volume of these cysts varied between 5 and 71 ml. Neonatal ovarian cysts disappear spontaneously frequently and rarely cause severe symptoms. The authors recommend follow-up by ultrasound as the primary modality. Surgical intervention is recommended only if the cyst is space-occupying and percutaneous puncture can not be performed or in the case of emergency. PMID- 1437360 TI - Literature in pediatric radiology. PMID- 1437359 TI - Urinary tract infection in infants in spite of prenatal diagnosis of hydronephrosis. AB - The efficacy of preventing neonatal urinary infection in infants by diagnosing hydronephrosis in the fetus on obstetrical ultrasonography was studied. 426 infants had uroradiologic evaluation between 1984 and June 1991 because they had hydronephrosis detected in utero. Thirteen with posterior urethral valves were excluded. Of the remaining 413, 13 (3.1%) presented with urinary infection in the first 6 months of life. Ten of the 13 were boys and 7 were not circumcised. Eleven of the 13 infants less than 2 months old were formula-fed. The causes of hydronephrosis were reflux alone in 6, ureteropelvic junction obstruction in 6 (with coexisting ipsilateral reflux in 4), and primary megaureter in 1. Ultrasonography alone was insufficient to exclude reflux. Amoxicillin-resistant bacteria were the causative organisms in all 10 for whom bacteriology data was available. Four categories of management failure were identified: 1) failure of communication of the prenatal findings, 2) antibiotics not prescribed, 3) antibiotics prescribed but not administered, and 4) infection in spite of continuous antibiotic prophylaxis. Uncircumcised formula-fed male infants with reflux seemed to be at special risk for infection. PMID- 1437361 TI - Cerebral magnetic resonance imaging (MRI) of very low birth weight infants at one year of corrected age. AB - Cerebral MRI was performed at 1.5 T in 27 infants with birth weight below 1500 grams at 1 year of corrected age. The images were compared to those reported on normal development at the same age. On T1 weighted images, 20 (74.1%) of the 27 infants showed myelin deposition different from what has been reported to be normal. Areas most affected were the central occipital white matter and the centrum semiovale. Both correspond to "watershed areas" known to be at risk for periventricular leukomalacia in preterm infants. T2-weighted images showed delayed myelination in the same areas as described for T1. In addition, two infants showed delayed myelination in the central occipital white matter and one in the centrum semiovale. Patchy focal abnormalities involving the white matter were seen in seven (25.9%) infants. Mild cerebral atrophy, mainly of the cortex was found in 10 (37.0%) infants. Irregular shape of the lateral ventricles, especially of the occipital horns was present in 12 infants (44.4%). 11 of these infants also had deviating changes in myelination. Only 2 infants (7.4%) had a normal MRI examination. Follow-up MRI examinations are needed to determine whether the high percentage of changes in myelination represent delayed development or brain damage in preterm infants. PMID- 1437362 TI - Choroid plexus cysts: a normal finding on ultrasound. AB - Within a period of 2.5 years, cystic structures in the choroid plexus were encountered at cerebral sonography in 70 neonates and babies (45 male, 25 female; 18 premature babies). Their prevalence in patients examined during the first 4 weeks of life (n = 55) was 3%. The size of the cysts ranged from 1-4 and, rarely, up to 7 mm. They were mostly solitary and unilateral. Follow-up sonograms over periods up to 13 months showed that most of the cysts persisted unchanged. A few disappeared (n = 7), while distinct increase in size was observed in 1 case. Since no additional sonographic changes were observed and none of the patients displayed any neurological abnormalities and no association existed with any other, particularly chromosomal, disease, such plexus cysts are postulated to represent a normal sonographic finding and do not require follow-up. PMID- 1437363 TI - Symptomatic third ventricular choroid plexus cysts. AB - We describe the imaging findings in 3 children with choroid plexus cysts (CPC) at the foramen of Monro. All CPC measured less than 2 cm and produced symptoms of raised intracranial pressure when located at the foramen of Monro where there was obstruction to the cerebrospinal fluid (CSF) flow. Among the imaging studies done on our patients, CPC were depicted best by cranial sonography and CT ventriculography and missed by standard CT and MRI. Misdiagnosis can lead to inappropriate shunting with adverse effects. Two of our patients had relief of symptoms after resection of the cyst. One patient with inoperable cardiac defects died and had no surgery performed. Serial CT and sonographic studies in this patient showed progression in the size of the cyst and ventriculomegaly. Cranial sonography and CT-ventriculography are the modalities of choice in evaluating ventriculomegaly when the diagnosis of occult obstructive CPC is entertained in children. Cranial sonography is indicated in infants with an open fontanelle and CT-ventriculography is reserved for older children with hydrocephalus which is not responding to shunting. PMID- 1437364 TI - Leptomeningeal cyst: early diagnosis by color Doppler imaging. AB - A newborn with a leptomeningeal cyst over the anterior fontanelle due to birth trauma is described. Color Doppler flow sonograms were helpful to diagnose the leptomeningocele in its early stages and to differentiate it from a cephalhematoma or subgaleal haemorrhage by demonstrating cerebro-fugal flow in an arterial connection between the extracranial fluid collection and the dural space. PMID- 1437365 TI - Exuberant blood flow in enlarged lymph nodes: findings on color flow Doppler. AB - Ten cases of adenopathy, 7 inflammatory and 3 lymphomatous in origin, with visible increased blood flow on color flow Doppler examination are presented. Although the ultrasonic demonstration of blood vessels in enlarged lymph nodes, both inflammatory and tumoral, is not new [1-5], we believe that this is the 1st definitive documentation with color flow Doppler. In some cases the degree of flow was striking, reflecting high velocity flow. This occurred both with inflammatory and lymphomatous nodes and we present our findings 1st to bring attention to them and 2nd to stimulate further investigation of the phenomenon. PMID- 1437366 TI - Sonographically demonstrated thickening of the renal pelvis in children. AB - Thickening of the wall of the renal pelvis has been attributed to infection, to rejection in allografts and to non-specific causes by different authors. We reviewed the clinical data, imaging studies and pathology of 35 patients with sonographically demonstrable thickening in 41 renal pelves of native kidneys. Our findings are that less than 50% of the patients had infection. The others had a wide variety of apparent causes for the thickening which include obstruction, surgery, edema induced by chemicals and other processes. Vesicoureteral reflux was demonstrated in 50% of the patients studied by cystography. We concluded that renal pelvic thickening is a non-specific finding. PMID- 1437367 TI - Ultrasound in the early diagnosis of congenital dislocation of the hip: the significance of hip stability versus acetabular morphology. AB - Recent studies have suggested that ultrasound examinations may improve diagnostic accuracy in congenital dislocation of the hip, but there is differing opinion whether ultrasound diagnosis should be based on morphology or stability. Ultrasound was added to the routine clinical screening in 1503 newborns (1291 girls and 212 boys). Hip morphology was classified according to Graf (type 1-4), while sonographic stability was based on a modified Barlow maneuver, and classified as stable, elastic deflection (normal finding), unstable (provocating a gap between the femoral head and the acetabulum) and dislocated. Among 80 morphologically dysplastic hips, 73 (91%) were sonographically unstable or dislocated, while seven dysplastic hips were stable. On the other hand, in 49% of the sonographic unstable hips (69 out of 142) the acetabulum was either normal or just physiologically immature. 38 of these hips were left untreated and normalized spontaneously. There was a close correlation between sonographically and clinically determined hip stability (gamma = 0.95). Our study shows that the majority of morphologically dysplastic hips is sonographically unstable or dislocated, but also that morphologically dysplastic hips may be stable. Morphologically normal hips showing minor sonographic instability do probably not require treatment, and thus morphology seems to be an important diagnostic criterion. PMID- 1437368 TI - Skeletal growth in cartilage-hair hypoplasia. A radiological study of 82 patients. AB - Cartilage-hair hypoplasia is a metaphyseal chondrodysplasia with short-limbed short stature. In childhood radiographs the metaphyseal regions of the tubular bones are widened, scalloped and irregularly sclerotic. We have analyzed radiological characteristics and skeletal growth in 149 radiographic surveys of 82 Finnish patients. All extremity long bones were affected and short for age. The growth failure was progressive. In the adults the median relative lengths were for the humerus -6.3 SD, radius -8.6 SD, ulna -6.7 SD, femur -9.7 SD, tibia 8.7 SD, and fibula -6.8 SD. the severity of the metaphyseal changes correlated with the degree of the growth failure. The skeletal age was markedly retarded in 14% of the patients. Caudal widening of the interpediculate distance in the lumbar spine was observed in 90% of the patients, but it tended to be less than normal. The sagittal diameter of the spinal canal was normal in the cervical region but decreased in the lumbar region. Mild scoliosis was observed in one fourth of the patients, and its incidence increased with age. Lumbar lordosis was moderately increased. Thoracic deformity was observed in 82% of the patients. The relative interorbital distance was increased with the median of +2.2 SD in the adults. PMID- 1437369 TI - Desbuquois syndrome presenting with severe neonatal dwarfism, spondylo-epiphyseal dysplasia and advanced carpal bone age. PMID- 1437370 TI - Value of MRI and MIBG-I123 scintigraphy in the diagnosis of spinal bone marrow involvement in neuroblastoma in children. AB - The results of MRI and MIBG scintigraphy performed on the spine of 14 children with neuroblastoma are reported. In 6 cases of diffuse spinal bone marrow tumor infiltration, diagnosis is easier with MIBG scintigraphy than with MRI. In 5 cases, MRI detected hyposignal of the vertebral body without any spinal abnormality on MIBG scintigraphy. A discussion of the reasons for negative MIBG scintigraphy is presented and in these 5 cases, it is suggested that a lateral view of MIBG scintigraphy and HMDP-Tc99m scintigraphy may be performed, even vertebral body biopsy in order to assess bone marrow tumoral infiltration. PMID- 1437371 TI - Eosinophilic granuloma simulating an aggressive rib neoplasm: CT evaluation. AB - Eosinophilic granuloma of bone can pose difficulties in diagnosis. We report a case of eosinophilic granuloma of rib origin in a child presenting with an enlarging chest mass whose appearance on computed tomography suggested Ewing sarcoma. Eosinophilic granuloma should be included in the differential diagnosis of an aggressive rib mass on CT in the pediatric patient. PMID- 1437372 TI - Primary endodermal sinus tumor of the liver detected by CT. AB - We report a case of primary endodermal sinus tumor of the liver. Endodermal sinus tumors are rare neoplasms which usually arise in the testis or ovary. Extragonadal endodermal sinus tumors are uncommon and primary tumors of the liver are very rare. The tumor was detected using CT and the diagnosis was made by percutaneous biopsy. PMID- 1437373 TI - Radiological assessment of duodenal calibre in congenital duodenal obstruction. AB - A review of barium meal studies in 32 cases of congenital intrinsic duodenal obstruction (CDO) from the Adelaide Children's Hospital was performed to assess and measure pre and post operative duodenal dilatation. Comparisons were made with a group of 153 normal barium studies from the same Hospital with a view to quantifying normal and abnormal proximal duodenal calibre. Duodenal size was expressed as a ratio D1/L1, (diameter of 1st part of duodenum/height of first lumbar vertebra). In this study a normal range of duodenal diameter was found to be 0.90 to 1.62 (+/- 2 SD from mean), with a mean of 1.26. The CDO patients recorded a range of postoperative ratios on first follow-up barium studies of between 1.2 and 4.5 with a mean of 2.28. Where serial studies had been performed, duodenal diameter was found to show some decrease in size postoperatively. In patients who underwent surgery for membrane obstruction there was a trend towards normalisation of duodenal diameter over time, compared with the atresia group. However, this difference did not reach statistical significance. PMID- 1437374 TI - Pelvic injuries in child abuse. AB - Three cases of child abuse are described in which pelvic injuries were prominent findings on radiologic examination: Two patients had pelvic fractures, and one was found to have heterotopic ossification of the soft tissues of the pelvis and thighs corresponding to extensive bruising in the pubic, genital, buttock, and thigh areas, resulting from physical and sexual abuse. These represent uncommon radiographic findings. Skeletal survey in cases of suspected child abuse should include the entire pelvis, and special attention should be paid to the ischiopubic rami the most common site of these rare pelvic injuries. PMID- 1437375 TI - Pediatric craniofacial surgery: comparison of milling and stereolithography for 3D model manufacturing. AB - To improve the planning phase for pediatric craniofacial surgery, 3D reconstructions of CT image series were performed on a personal computer. For construction of true models of the surgical site, two concepts were pursued. CT image data of six patients were used for model manufacturing by a conventional 2 1/2 axis milling system. The material used was polyurethane foam. Alternatively, in one patient a stereolithography was produced on the basis of the 3D reconstructed CT data. This new manufacturing device uses a photocurable monomer, hardened by a UV-laser. The spatial resolution of the system is about 0.1 mm. 3D reconstructions were performed on a personal computer. Data were then transferred into a surface oriented structure to control a stereolithographic modeling device. Time for transfer was 70 min. The production of the modelled cranium took a total time of 59 h. Accuracy was found to be much higher in stereolithography than in milled models. The model served for surgical planning. The long time for production was caused by inadequate computer capacities, which are configured for much less complex objects in computer aided design. Furthermore the programs for the machine control are optimized for technical purposes. If these conditions are improved, stereolithography could be an attractive alternative to milling of medical models. PMID- 1437376 TI - The fibrous metaphyseal defect in early stage. Differential diagnosis to metaphysitis. AB - In a 22-month-old boy a fibrous metaphyseal defect (FMD) was diagnosed by radiological follow-up examinations. The initial radiological finding could not be differentiated from metaphysitis because of its early manifestation and stage. Eleven months later, magnetic resonance imaging (MRI) with Gadolinium (Gd)-DTPA demonstrated a small central area of increased signal intensity. Based on known angiographic findings with fibrous metaphyseal defects, one may hypothesize that this is best explained by a hypervascularized area. PMID- 1437378 TI - Asymptomatic myelolipoma of the adrenal. AB - Myelolipoma of the adrenal gland is a rare benign tumour which seldom produces symptoms unless it attains considerable size or hemorrhages into itself. Histologically the tumor is composed of varying proportions of fat and bone marrow elements. We present a case of a male child, with homozygous beta thalassemia and asymptomatic myelolipoma. PMID- 1437377 TI - MR imaging of breast hemangioma in female infants. AB - Breast hemangioma in female infants is a rare benign lesion, prone to spontaneous regression. But when the lesion regresses there is a risk of breast atrophy if the breast bud is included in or very close to the hemangioma. A trial of corticosteroid therapy could be proposed to prevent this risk, but one must be sure that the breast bud is included in or very close to the hemangioma before treatment. We studied 4 children with breast hemangioma to evaluate the ability of MR Imaging in the diagnosis of breast bud inclusion. 0.5 Tesla axial Spin Echo T2-weighted images (TR = 2000 ms; TE = 120 ms) clearly depicted interface between high signal appearance of hemangioma and hypo-intensity of the breast bud: in our four patients we were able to determine whether or not the hemangioma involved the breast bud. Our preliminary study seems to demonstrate that MR imaging is a valuable imaging technique to determine which patients could be eligible for a trial of corticosteroid therapy. PMID- 1437379 TI - Inflammatory pseudotumor of the lung manifesting as a posterior mediastinal mass. AB - A case of inflammatory pseudotumor of the lung in a 6-year-old boy is presented. The respiratory illness presented as a mycoplasma pneumonia and there had been a similar episode of mycoplasma pneumonia one and a half years previously. Computed tomography revealed a large, calcified right posterior mediastinal mass and exploratory thoracotomy revealed a large posterior mediastinal mass that had an endobronchial component and grew exophytically from the lung. The present case suggests that inflammatory pseudotumor of the lung can manifest as a mediastinal mass and could be associated with mycoplasma pneumonia infection. PMID- 1437380 TI - Ultrasound diagnosis of an atypical pneumomediastinum. AB - The diagnosis of an atypical pneumomediastinum in a newborn was confirmed by ultrasound where an echogenic rim of air was noted around the heart. Ultrasound is suggested as an alternative to a decubitus film in differentiating between a pneumomediastinum (which usually resolves spontaneously) and a medial pneumothorax (which requires drainage). PMID- 1437381 TI - Two unusual cases of nephrocalcinosis in infancy. AB - Nephrocalcinosis is uncommon in childhood, the main causes are renal tubular acidosis, hyperparathyroidism and medullary sponge kidney. It is also seen where there is hypercalcaemia or hypercalciuria of any aetiology; We report nephrocalcinosis in an 18-month-old infant with metaphyseal chondrodysplasia type Jansen and also in a neonate with McCune Albright syndrome who displayed atypical skeletal appearances and had multiple ovarian cysts. PMID- 1437382 TI - MR imaging and sonography of Gartner's duct cyst and single ectopic ureter with ipsilateral renal dysplasia. AB - An 8-year-old girl with a rare anomaly of a single ectopic ureter to the Gartner's duct cyst and ipsilateral renal dysplasia is presented. MR imaging and ultrasound were utilized to make the diagnosis. PMID- 1437383 TI - Radiographic findings in Wiedemann-Rautenstrauch syndrome. AB - We describe a girl who presents the features of Wiedemann-Rautenstrauch syndrome. This autosomal recessive condition has characteristic radiographic findings which can be considered manifestations of the syndrome. PMID- 1437384 TI - Cephalo-skeletal dysplasia and microcephalic osteodysplastic primordial dwarfism. PMID- 1437385 TI - American Pediatric Society presidential address 1992: genetics--the science and medicine of the future. PMID- 1437386 TI - Rational design of conjugate vaccines. AB - Whereas bacterial polysaccharides, classified as T-cell-independent antigens, elicit protective antibodies in adults, booster injections fail to produce an augmented response or promote antibody class switching. Because T-cell-dependent antigens, typically proteins, both produce boosted antibody levels and promote antibody class switching, it has been considered highly desirable to attempt to convert the T-cell-independent polysaccharide antigens into T-cell-dependent antigens, particularly for use in high-risk groups. A number of clinical trials now report the efficacy of conjugate vaccines in inducing the production of antibody in response to a number of previously poorly immunogenic--mainly T-cell independent--antigens. In addition to conjugate vaccines containing bacterial polysaccharides, vaccines containing relevant peptides from a variety of pathogens are also being formulated and investigated. Questions remain, however, regarding their synthesis, use, and efficacy. The best ages for vaccine administration and selection of the optimal protein carrier are still under investigation, as are questions regarding the use of adjuvants, which can greatly affect the vaccine's potency. Spacing and size of epitope and size and composition of the final structure also must be considered; the importance of molecular size and aggregation of antigen in increasing immunogenicity have been well documented. These questions must be addressed for the much-needed development of conjugate vaccines against some common infections worldwide, including malaria, bacterial meningitis, and infections from Pseudomonas aeruginosa and Neisseria gonorrhoeae because of increasing susceptibility to these infections and resistance of the pathogens to chemotherapeutic agents and/or antibiotics. PMID- 1437387 TI - In situ morphology of the ductus venosus and related vessels in the fetal and neonatal rat. AB - In situ cross-sectional morphology of the ductus venosus and related vessels was studied after rapid whole-body freezing of the fetal and neonatal rat. In the fetus, the ductus venosus was open widely, connecting the umbilical sinus and the inferior vena cava. The diameter of the ductus venosus was 50% of the diameter of the umbilical sinus. The ductus venous joined the left dorsal side of the inferior vena cava. A thin, short, membrane-like edge was present at the inner junction of the ductus venosus and the inferior vena cava, presumably effecting laminar flow of the ductus venosus blood to the left side of the thoracic inferior vena cava. A very prominent eustachian valve was present at the junction of the inferior vena cava and the right atrium, presumably directing its flow to the opening of the foramen ovale. After birth, the ductus venosus narrowed rapidly and closed completely in 2 d. The closing ductus venosus was tubular, with the cranial end slightly wider than the caudal portion. Localized constriction was not present. These observations showed the structural substrate for preferential flow from the ductus venosus to the foramen ovale and left atrium in the fetus and did not support localized sphincter mechanism in postnatal closure of the ductus venosus. PMID- 1437388 TI - Fate of the atrioventricular endocardial cushions in the developing chick heart. AB - To determine the fate of the atrioventricular endocardial cushions in cardiac development, we used staining methods for extracellular fibronectin, which is abundant in the endocardial cushions, and actin, which is abundant in the myocytes. White Leghorn chick embryo hearts were harvested at Hamburger and Hamilton stages 26 to 36, and serial sections of the atrioventricular valve region were stained. Before atrioventricular valve formation, fibronectin and actin staining reveal separation between the fibronectin-rich endocardial cushions and the actin-rich myocardial layer. The developing mitral valve leaflets at all of the observed stages contain a fibronectin-rich matrix but no actin-rich myocytes. In contrast, the tricuspid band includes both fibronectin matrix and actin-rich cells. We conclude that the mitral valve leaflets in the chick form predominantly from the endocardial cushion tissue, and the tricuspid band receives contributions from both the endocardial cushions and surrounding myocardium. PMID- 1437389 TI - Nitrofen-induced diaphragmatic hernias in rats: pulmonary antioxidant enzyme activities. AB - We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4 dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage. PMID- 1437390 TI - Recycling of glutathione during oxidative stress in erythrocytes of the newborn. AB - The ability of erythrocytes from newborn babies and adults to maintain reduced glutathione levels during oxidative stress was studied. In vitro incubation of erythrocytes with H2O2, with or without inactivation of catalase, caused a rapid depletion of reduced glutathione (GSH) and concomitant accumulation of oxidized glutathione followed by recovery of GSH and fall of oxidized glutathione to initial values in all subjects. Inactivation of catalase resulted in a 50% loss of intracellular glutathione (p less than 0.005), a larger maximum GSH depletion (p less than 0.05), and a longer GSH recovery time (p less than 0.005). Erythrocytes from newborn babies showed a smaller maximum GSH depletion (p less than 0.05) and a shorter GSH recovery time (p less than 0.005) compared with those from adults. These differences between the newborn and adult groups persisted after inactivation of catalase. An increase in maximum GSH depletion and GSH recovery time (p less than 0.005) was observed when a lower hematocrit was used for these GSH recovery studies. Effective glutathione recycling in erythrocytes may protect immature tissues of the newborn baby from peroxidative damage. PMID- 1437391 TI - Small preterm infants (less than or equal to 1500 g) have only a sustained decrease in ventilation in response to hypoxia. AB - The classic "biphasic" ventilatory response to 15% O2 was previously observed in preterm infants who were large compared with those in the intensive care nursery today. We hypothesized that in the smaller infant (less than or equal to 1500 g) the response might be closer to that of the fetus, with no initial increase in ventilation. Thus, we studied 14 healthy preterm infants less than or equal to 1500 g [birth weight 1200 +/- 63 g (mean +/- SEM); gestational age 29 +/- 0.4 wk; postnatal age 17 +/- 3 d] during rapid eye movement and quiet sleep. Ventilation was measured using a nosepiece and a flow-through system. Sleep states were defined using EEG, electro-oculogram, and body movements. After a control period in 21% O2 (3 min), infants breathed 15% O2 for 5 min. In rapid eye movement sleep, minute ventilation decreased from 0.186 +/- 0.020 (control) to 0.178 +/- 0.021 (30 s), to 0.171 +/- 0.017 (1 min; p = 0.03), to 0.145 +/- 0.016 (3 min; p = 0.002), and to 0.129 +/- 0.011 l.min-1.kg-1 (5 min; p = 0.004). In quiet sleep, it decreased from 0.173 +/- 0.019 (control) to 0.164 +/- 0.019 (30 s), to 0.166 +/- 0.019 (1 min), to 0.148 +/- 0.013 (3 min; p = 0.03), and to 0.146 +/- 0.012 l.min-1.kg-1 (5 min; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437392 TI - Prenatal thyroid releasing hormone and thyroid releasing hormone plus dexamethasone lessen the survival of newborn rats during prolonged high O2 exposure. AB - Newborn rats prenatally treated with TRH or the combination of TRH + DEX have lower lung antioxidant enzyme activities at birth than control newborns but are able to induce an adaptive antioxidant enzyme response to hyperoxic exposure of similar or even greater magnitude compared to O2 control offspring. Because of this greater antioxidant enzyme response, we hypothesized that the hormonally pretreated newborns might demonstrate superior tolerance to prolonged high O2 exposure. However, when placed in greater than 95% O2 at birth, the survival rates were consistently lower in the TRH- and TRH + DEX-treated pups at all time periods in hyperoxia from 9 d [control = 74 of 92 (80%); TRH + DEX = 32 of 47 (68%); TRH = 29 of 48 (60%); p less than 0.05] to 14 d [control = 43 of 92 (47%); TRH + DEX = 11 of 47 (23%); TRH = nine of 48 (19%); (p less than 0.05)]. Other evidence of poorer O2 tolerance in the prenatal hormone-treated pups included a greater incidence of intraalveolar edema and elevated lung conjugated dienes, an index of lipid peroxidation, at 3, 5, and 7 d of O2 exposure. There was also a persistent elevation in 3,5,3'-triiodo-L-thyronine and thyroxine serum levels in the 10-d-old TRH-treated offspring. We conclude that prenatal TRH treatment, possibly working through the secretion of 3,5,3'-triiodo-L-thyronine and thyroxine, has some important lasting postnatal effect (not completely reversed by dexamethasone) that predisposes newborn rats to greater O2 radical-induced lung sequelae of prolonged hyperoxic exposure. PMID- 1437393 TI - Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine. AB - The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437394 TI - The relationship between environmental temperature, metabolic rate, sleep state, and evaporative water loss in infants from birth to three months. AB - We have investigated the effect of changing environmental temperature on metabolic rate, sleep state, and water loss in a longitudinal study of 22 lightly clothed babies from 2 d to 3 mo of age. Studies were performed in a modified barometric plethysmograph while recording sleep state, oxygen consumption, and skin and axillary temperatures. Oxygen consumption was higher in rapid eye movement sleep than in quiet sleep at all ages and varied widely between infants at each temperature. Within the first week, there was a 19% rise in oxygen consumption on cooling to 19-22 degrees C during rapid eye movement sleep and a 6% rise during quiet sleep. The median duration of quiet sleep periods was reduced from 17 to 12 min on cooling within the first week. No such change was seen at 1, 2, and 3 mo. Axillary temperature was reduced at 3 mo during cooling. This may be a part of normal patterns of change in temperature during sleep, unrelated to cooling. At each age, total evaporative water loss fell linearly with falling environmental temperature both within and below the temperature range at which metabolic rate was minimal. The evaporative water losses were greater than expected and suggested that sweating was occurring, both at temperatures at which metabolic rate was minimal and at those at which it was increased. The metabolic response to cooling and the process of sweating appear to be in dynamic equilibrium across this temperature range. Thus, it was not possible to define a temperature range over which both metabolic rate and evaporative water loss were at minimum values. PMID- 1437395 TI - Expression of pulmonary metallothionein genes in late gestational lambs. AB - Metallothioneins (MT) are low molecular weight proteins that are important in providing protection against heavy metals such as cadmium. Other precise physiologic roles for this family of proteins are less clear, but fetal hepatic cell proliferation and differentiation may be regulated through changes in MT levels and attendant MT-mediated regulation of zinc levels. The role of MT in other developing tissue, most notably lung, is far less clear. Although expression of MT has been reported to be extremely low in early postnatal and mature lung, we hypothesized that MT has a more ubiquitous role in organ development and that pulmonary MT levels may be elevated during periods of rapid lung growth. Thus, we studied expression of MT in late-gestation fetal lambs. Sheep are particularly useful because alveolarization of lung parenchyma occurs before birth (by d 120 of a normal 147-d gestation). Immunoreactive MT was localized to bronchial epithelium of fetal, newborn, and mature sheep. The intensity of staining was greatest in the 130-d gestational age (saccular) lung, where positive reaction product was noted in the cytoplasm and nucleus of alveolar epithelial and interstitial cells. We next evaluated MT expression in developing lung tissue using Northern blot analysis and 32P-cDNA probes against the 3'-untranslated regions of mRNA encoding each of four known functional sheep MT (sMT) isoforms. Expression of sMT-II, sMT-Ia, and sMT-Ib was restricted to the saccular stage (120-132 d gestational age), and sMT-Ic mRNA was not detected in pulmonary samples from any stage of development.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437396 TI - Activation of the plasma kallikrein-kinin system in respiratory distress syndrome. AB - Components of the plasma kallikrein-kinin and fibrinolytic systems together with antithrombin III were measured the first days postpartum in 13 premature babies with severe respiratory distress syndrome (RDS). Seven of the patients received a single dose of porcine surfactant (Curosurf) as rescue treatment. Nine premature babies without lung disease or any other complicating disease served as controls. There were no differences in prekallikrein values between surfactant treated and non-treated RDS babies during the first 4 d postpartum. The controls had, however, significantly higher prekallikrein values than the RDS babies already at the first day of age (mean +/- SD 32 +/- 8% in controls versus 22 +/- 6 and 21.5 +/- 5% in the treated and nontreated RDS groups, respectively). Plasma kallikrein activities did not differ between RDS and control patients. Plasma kallikrein inhibition values, which increased steadily in all groups, were lower in the RDS babies treated with surfactant than in controls at d 2 and 4. The degree of degradation of plasma high molecular weight kininogen was measured in RDS patients treated with surfactant and was significantly higher when compared with controls at d 1, demonstrating an increased proteolysis of kininogen to kinin early in RDS. There were no differences in plasminogen and plasmin values between RDS and control babies. This study shows that the plasma kallikrein-kinin system is activated in RDS. This system as well as the fibrinolytic system does not seem to be influenced by rescue instillation of a single dose of porcine surfactant into the lungs of premature babies with RDS. PMID- 1437397 TI - Differential effects of short and long durations of insulin-induced maternal hypoglycemia upon fetal rat tissue growth and glucose utilization. AB - We studied the effects of short and long durations of insulin-induced maternal hypoglycemia upon in vivo glucose utilization of several fetal tissues in the rat. Osmotic minipumps filled with insulin were implanted in pregnant rats on d 15 or 18 of gestation (term 21.5 d), and radiolabeled 2-deoxyglucose was used to measure relative glucose utilization rates (rGU) of fetal liver, lung, muscle, kidney, heart, placenta, and brain on d 20 of gestation after 2 or 5 d of hypoglycemia. Maternal plasma glucose concentrations decreased within 24 h of pump placement and remained less than controls throughout gestation. Fetal plasma glucose and insulin concentrations on d 20 were equally reduced after 2 and 5 d of hypoglycemia. Both 2 and 5 d of hypoglycemia were associated with significant reductions in the rGU of fetal liver, lung, and muscle. Reductions in fetal kidney rGU also occurred after 2 and 5 d of hypoglycemia but to a smaller degree. rGU of fetal heart was reduced after 2 d of hypoglycemia, but was normal after 5 d of hypoglycemia. Both 2 and 5 d of hypoglycemia were associated with increased rGU of fetal brain. Five d, but not 2 d of hypoglycemia resulted in decreased fetal weight on d 20 of gestation. However, at term, newborn pups delivered of hypoglycemic mothers weighed significantly less than controls regardless of the timing of minipump placement. Liver, lung, and carcass of these growth-retarded pups weighed less than control tissues, whereas kidney, heart, and brain weights were not affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437398 TI - The metabolism of free fatty acids and triacylglycerols by the fetal liver in a guinea pig model of intrauterine growth retardation. AB - The aim of this study was to determine whether intrauterine growth retardation (IUGR) is associated with an alteration in hepatic lipid metabolism. IUGR was induced in 25 guinea pigs by uterine artery ligation on gestational d 30. On d 62, after anesthesia, an infusion of [1-14C]-palmitic acid was given. Fetuses were exposed at 15, 30, and 45 min, and simultaneous maternal and umbilical venous blood samples were taken. Livers were divided into right lobe, right and left sublobes of the quadrate lobe, and left lobe. In control fetuses, plasma radiolipids rose in parallel with, but were about half the value of, maternal levels. In IUGR fetuses, plasma radiolipids were lower than in controls at 15 and 30 min but were comparable at 45 min. Most of the radiolipid in the maternal plasma was FFA, with only 6% incorporated into triglycerides at 45 min. In control and IUGR fetal plasmas, 36-37% of the radiolipid was triglycerides by 45 min. Radiolabel incorporation into the right lobe was less than into the left lobe and left half of the quadrate lobe in control and IUGR fetuses. Compared with controls, radiolabel incorporation in IUGR fetuses was less in some or all liver lobes at each time point. The proportion of label associated with FFA and triglycerides did not vary with time, between lobes, or between control and IUGR fetuses. The difference in uptake between lobes reflects their blood supply, implying that most FFA is extracted during the first passage of the umbilical venous blood. Growth retardation was not associated with compromised hepatic FFA metabolism. PMID- 1437399 TI - Changes in protein turnover after the introduction of parenteral nutrition in premature infants: comparison of breast milk and egg protein-based amino acid solutions. AB - Rates of protein turnover were measured in 20 infants receiving either Vamin Infant (group A) or Vamin 9 glucose (group B) as the amino acid source in total parenteral nutrition. A constant infusion of L-[1-13C]leucine was used to measure whole body leucine flux, and leucine oxidation rates were derived from measurements of total urinary nitrogen excretion. Infants were first studied when receiving only i.v. glucose and again on each of the next 4 d as total parenteral nutrition was gradually increased to a maximum of 430 mg nitrogen/kg/d and 90 nonprotein kcal/kg/d. Net protein gain and protein synthesis and breakdown rates increased progressively for all infants taken together over the study period as i.v. nutrition was increasing (p less than 0.001). There were no differences between groups in the changes in net protein gain and rates of protein synthesis and breakdown throughout the study period. Nitrogen retention on d 5 for the two groups was similar (60 +/- 16% and 67 +/- 11% in groups A and B, respectively). In a subgroup of infants, measurements were repeated on d 8, when the intake had been constant for 3 d. Protein retention was the same as on d 5, but both synthesis and breakdown were increased. It is concluded that rates of protein turnover increase significantly in response to increasing i.v. nutrition and that this elevation was not influenced by the composition of the amino acid mixture given. PMID- 1437400 TI - Low prevalence of autoantibodies to the insulin-like growth factor I receptor in children with short stature. AB - Inhibition of IGF-I action by circulating IGF-I receptor autoantibodies is a potential mechanism of IGF-I resistance in growing children. To define the prevalence of IGF-I receptor antibodies in short-statured children, we have examined serum and plasma samples from a well-characterized group of 34 short, prepubertal, growth hormone-sufficient children and three growth hormone deficient children. IGF-I receptor purified from human placental membranes was radioiodinated by the solid phase radioiodination method. Serum from a patient with severe insulin resistance immunoprecipitated 28.9-44.7% of the 125I-labeled IGF-I receptor. The ranges (mean +/- 3 SD) of 125I-labeled IGF-I receptor immunoprecipitated by 1:10 diluted and by undiluted nonimmune human serum were 1.99 +/- 0.63% and 4.42 +/- 1.32%, respectively. Immunoprecipitation of the 125I labeled IGF-I receptor by eight samples from six children was greater than 3 SD above the mean when assayed at a 1:10 dilution. Nevertheless, when assayed undiluted, only one of these samples immunoprecipitated slightly more 125I labeled IGF-I receptor than nonimmune serum. We conclude from these data that immunoprecipitating autoantibodies to the IGF-I receptor are not commonly present in short-statured children. PMID- 1437401 TI - Role of tumor necrosis factor-alpha and interferon-gamma in newborn host defense against Listeria monocytogenes infection. AB - The fetus and newborn are particularly susceptible to Listeria monocytogenes infection. We used a newborn rat animal model to investigate neonatal host defense against Listeria. In this animal model, newborn (3-d-old) rats are more susceptible to L. monocytogenes than older animals. Juvenile (23-d-old) L. monocytogenes-infected rats pretreated with lipopolysaccharide (LPS) had a lower bacterial load in blood than control animals, whereas LPS pretreated newborn rats had a higher bacterial load. Because LPS is a potent inducer of tumor necrosis factor (TNF) and TNF enhances host defense against this organism in adult animals, we assessed TNF content in splenic homogenates for animals of different ages. The age at which TNF was detectable in L. monocytogenes-Infected rats corresponded to the age at which LPS became active in preventing severe bacteremia. TNF was less than 1 unit/mL in splenic homogenates taken from rats less than 8 d of age, whereas 16-d-old rats infected with L. monocytogenes 1 d earlier had greater than 80 units/mL (p less than 0.0001 for 3-d-old versus 16-d old rats). We also assessed the responsiveness of rats to exogenous TNF-alpha. Juvenile rats pretreated with TNF-alpha before L. monocytogenes infection had decreased bacterial load in spleen (p less than 0.02 versus controls) and better survival at 7 d (p less than 0.05 versus controls), whereas newborn rats did not improve with TNF-alpha pretreatment (p greater than 0.05 treated versus controls for splenic bacterial load and 7-d survival).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437402 TI - Characteristics of L-citrulline transport across rat small intestine in vitro. AB - The amino acid L-citrulline is an important intermediate of urea cycle and a key precursor for arginine biosynthesis. We have examined the characteristics of citrulline transport across the everted sacs of the rat small intestine. Our studies suggest that the optimal site of citrulline absorption is middle to lower ileum. It shows active transport, and this transport is predominantly Na+ dependent. Its uptake is significantly inhibited by ouabain, dinitrophenol, sodium azide, and sodium cyanide. Kinetic estimation reveal an apparent substrate concentration at 1/2 maximum velocity of 4.10 +/- 0.86 mM and a Vmax of 18.7 +/- 1.66 mumol/g wet weight tissue/30 min. Analog inhibition studies suggest that citrulline may share the neutral brush border system described for the mucosal brush border membranes of the rabbit jejunum or a system analogous to system ASC described for nonepithelial cells and for basolateral membranes of certain epithelia. In conclusion, the rat small intestine has developed a specific carrier-mediated, Na(+)-dependent pathway for citrulline absorption. PMID- 1437403 TI - Prolidase deficiency in cultured human fibroblasts: biochemical pathology and iminodipeptide-enhanced growth. AB - Prolidase deficiency is a rare autosomal recessive disorder characterized by iminodipeptiduria, severe skin ulcers, recurrent infections, and mental retardation. The enzyme prolidase hydrolyzes dipeptides containing C-terminal proline or hydroxyproline. We investigated the metabolic abnormality caused by prolidase deficiency in human cultured skin fibroblasts. These studies were undertaken to test biochemical hypotheses regarding the metabolic origins of the skin lesion occurring in this disease. Our results indicate that prolidase plays a major role in the recycling of dipeptide-bound proline. Control fibroblasts were able to use iminodipeptides in lieu of proline to sustain normal growth, whereas cells homozygous for the prolidase deficiency mutation were not. Proline derived from iminodipeptides diluted incorporation of radiolabeled extracellular proline into cellular protein in normal cells but not in mutant cells. Substitution of a prolidase-free medium for FCS did not affect the growth rate of control cell lines but increased the doubling time of prolidase-deficient cells by 19% (28% in the presence of iminodipeptides). Iminodipeptides added to control and mutant cells maintained in serum-free medium showed no adverse effects on protein synthesis. These results are consistent with a mechanism of biochemical pathology in which proline deprivation caused by the enzyme deficit is a primary cause of damage to skin cells. Prolidase regulation by product and substrate was studied. A 44% decrease in activity was observed in fibroblasts grown for 3 wk in proline-containing medium relative to proline-free medium. However, cells grown in medium in which iminodipeptides replaced proline showed no significant difference in prolidase activity. PMID- 1437404 TI - Postischemic hyperglycemia is not protective to the neonatal rat brain. AB - Brain glucose concentration during and after hypoxia-ischemia may be one of the variables affecting outcome of asphyxial insults. Glucose given before global ischemic forebrain injury to adult rats increases morphologic brain damage, and postischemic insulin administration reduces selective neuronal necrosis and cortical infarction. Because glucose infusions are routinely used in the clinical management of perinatal asphyxia, we evaluated the role of glucose administration after ischemic neuronal damage to neonatal rat brain. Sprague-Dawley rat pups (postnatal d 7) were subjected to left common carotid artery ligation followed by 2.5 h of 8% oxygen (Levine procedure). The experimental group was subdivided so that pups received either systemic injections of glucose or saline immediately after the hypoxic insult. Animals were killed on postnatal d 12 and brain areas of ipsi- and contralateral cortex and caudate were calculated from camera lucida tracings. There was no significant difference in size of brain infarction between postischemic glucose-treated and post-ischemic saline-treated pups. However, hypoxic-ischemic brains did show more severe neuronal damage when hyperglycemia was induced after asphyxia. Because post-ischemic hyperglycemia does not attenuate and may exacerbate injury, we recommend careful monitoring of blood glucose so that hyperglycemia does not occur during resuscitation of asphyxiated infants. PMID- 1437405 TI - Gaucher disease in the neonate: a distinct Gaucher phenotype is analogous to a mouse model created by targeted disruption of the glucocerebrosidase gene. AB - A group of neonates with Gaucher disease with a particularly devastating clinical course is described. The phenotype of these infants is analogous to that of a Gaucher mouse, which was created by targeted disruption of the mouse glucocerebroside gene. Similar to the homozygous mutant mice with glucocerebrosidase deficiency, these infants present at or shortly after birth, have rapidly progressing fulminant disease, and many have associated ichthyotic skin and/or hydrops fetalis. This transgenetic mouse model of Gaucher disease has helped us to appreciate a distinct Gaucher phenotype. Potentially, as this technology is applied to create other animal models of metabolic diseases, it may enable the recognition of other, as yet unappreciated presentations of inherited disorders. PMID- 1437406 TI - Howland Award presentation to Gilbert B. Forbes. PMID- 1437407 TI - Acceptance of the Howland Award. PMID- 1437408 TI - Research in behavioral-developmental pediatrics: new frontiers and elusive boundaries. PMID- 1437409 TI - The biobehavioral interface in behavioral pediatrics. PMID- 1437410 TI - Health consequences of behaviors: injury as a model. AB - Injury is the third leading cause of death in the United States and the leading cause for children, adolescents, and young adults. Injury results from multiple factors and so may its prevention. The first and simplest approach toward preventing injuries has been to innovatively and aggressively apply a traditional public health model. Strategically, the goal has been to remove harmful agents of injury and to make the environment safer. Tactics such as public information, product regulation, legislative action, and the like have been credited with reductions in mortality and morbidity. To expand our understanding and our prevention strategies across multiple injuries, other scientific knowledge bases and intervention models from fields such as psychology and child development are being used to study childhood injury. These approaches show that in addition to environmental determinants, psychosocial factors involving both the care giver and the child are related to injury. The research programs described here illustrate the advantage of investigating psychosocial factors at both molar and molecular levels. General characteristics of mothers and children related to injury help define families at risk, as well as suggesting vehicles for intervention. Behavioral factors influencing risk perception highlight the etiology of increased risk in adolescence. Injury episodes, even slight, as well as "near injuries" and dangerous and risky behavior can be quantified and analyzed by retrospective ("postmortem") approaches yielding data on commonly occurring consequences (and the lack thereof) for minor injury. Finally, approaches that simulate dangerous situations can identify interaction patterns that result in childhood injury. Based on such research, we are coming to view injuries as the result of patterns of behaviors that develop and persist over time, and as such these patterns can be detected and, one hopes, altered before a serious medical event occurs. The role of the pediatrician after injury occurs is clear. With regard to prevention of injuries, pediatricians' roles are being defined by those individuals who have begun to investigate causes, educate families, and advocate for regulation and prevention. However, like the causes and methods for prevention, the disciplines involved in the study and prevention of injury are multiple. Such a multidisciplinary approach that considers multiple factors, theories, models, and interventions to prevent injury may be the approach that is as simple as possible. PMID- 1437411 TI - Behavioral consequences of illness: childhood asthma as a model. AB - Several areas of research on childhood asthma are discussed within a transactional model of asthma. The model emphasizes the multidirectional influences that affect the severity of asthma and associated behavioral disability. The initial focus is on how the clinical presentation and morbidity of asthma are affected both by somatic predisposition and by interactions with multiple internal and external elements. Specific elements include emotional factors, neuroimmunology, temperament, and medication side effects. Second, the impact of asthma on the child, his or her family, and segments of the community are described, as are consequences of the disorder on quality of life. Third, there is a synopsis of preventative interventions for reducing the medical and behavioral impact of childhood asthma. The motif is that the interaction of medical and behavioral procedures can improve the management of asthma while consequences of the disorder are mollified. Finally, as examples of a transactional model of asthma, self-management programs for teaching children to become partners with their physicians in establishing and maintaining control over the disorder are described. A representative of self-management--the ACT (Asthma Care Training) program--is described, along with the impact such programs have on children, their families, and institutions. The conclusion emphasizes that asthma is a complicated and unpredictable disorder that puzzles physicians, behavioral scientists, and patients. Although new treatments may be over the horizon, controlling childhood asthma and its consequences currently rests on the cooperation and increased interaction of medical and behavioral scientists. PMID- 1437412 TI - Pediatric pain: interacting behavioral and physical factors. AB - Pain in infants, children, and adolescents warrants study from a developmental, behavioral, and physiological perspective because maturation of physical, emotional, and cognitive systems influences the way in which pain is experienced and expressed. Pediatric pain is an underdeveloped area ripe for study within the realm of developmental and behavioral pediatrics, as noted by documentation of its undertreatment in children. The focus of this paper is to present issues relevant to the study of pain in children, using the example of the recurrent abdominal pain syndrome to illustrate points regarding epidemiology, assessment, and intervention. It is the opinion of these authors that pediatric pain must be understood from a developmental perspective in both clinical and nonclinical populations of children. Multidisciplinary approaches to research in pain aids in understanding the development of nociceptive transmission and inhibitory systems, the development of pain expression, and the influence of context on pain experience and behavior. The goal of research in pediatric pain is to understand these systems within a developmental context so that preventive and therapeutic intervention strategies can be developed to reduce children's distress and pain related disability. PMID- 1437413 TI - Conceptual and methodological issues for behavioral pediatrics research. AB - Three prescriptions are made to improve behavioral pediatrics research: (1) Focus behavioral pediatrics on preventive research from environmental and social perspectives. (2) Ground research questions more extensively within a conceptual framework. (3) Enhance research quality with reliable, valid measurement. Conceptual and methodological improvements in research will facilitate integration of the multidisciplinary, multimethodological, and multitheoretical scope of behavioral pediatrics and further its contributions to science. PMID- 1437414 TI - The future of behavioral pediatrics research: moving right along. PMID- 1437415 TI - American Academy of Pediatrics. Committee on Sports Medicine and Fitness. Fitness, activity, and sports participation in the preschool child. PMID- 1437416 TI - Earrings: a source of bloodborne infections? PMID- 1437417 TI - Gastric juice, drugs, and end-tidal carbon dioxide detectors. PMID- 1437418 TI - Money alone won't do it. PMID- 1437419 TI - Is ear pulling associated with ear infection? PMID- 1437420 TI - Lack of money--barrier to immunization. PMID- 1437421 TI - Lead ingestion and x-rays. PMID- 1437422 TI - Annual summary of vital statistics--1991. AB - Between 1990 and 1991, provisional data show that the infant mortality rate decreased again, from 9.1 to 8.9, a decline of 2% in contrast to the 7% decline from 1989 to 1990. Birth, death, and marriage rates were also lower, but the divorce rate stayed at about the same level as in 1990. Natural increase in the population, excess of births over deaths, was less than 2 million, 4% less than the increase in 1990. Detailed analysis of changes and of the influence of factors like age and race requires final data; at the time of preparation of this report final birth and death data were available only through 1989. For a variety of reasons, including staff shortages and delays in receipt of state data by the National Center for Health Statistics (NCHS), final data for 1990, which would usually have been available in late August 1992, are not expected before early 1993. Unlike recent years, the decline in the infant mortality rate was only in the neonatal component, which decreased 3.6%. Postneonatal mortality increased, for the first time in many years, by 1.6%, suggesting that the decline in the total is related more to therapeutic advances in neonatology than to improved prevention. Internationally, newly independent Latvia was added to the list of countries with rates less than 15, but Costa Rica was deleted. With the reunification of Germany the list shrank to 28 and, by default, the United States moved up from 21st to 20th. Some 12.5 million births, less than 9% of the world total, took place in countries with under-5 mortality rates of less than 20 per 1000. At the other end of the scale, 42% of the world's births occurred in countries with under-5 mortality rates of more than 140 per 1000. The median under-5 mortality rate for those countries in 1990 was 189 per 1000, meaning that almost 20% of the infants born alive in these countries died before their fifth birthday. PMID- 1437423 TI - Fever revisited. PMID- 1437424 TI - Fever phobia: the pediatrician's contribution. AB - Fever phobia, the exaggerated fear of fever, is found among parents of all socioeconomic classes. Pediatricians may inadvertently contribute to fever phobia if their practice and educational message are incongruent. To determine how pediatricians treat fever in their practice, the authors sent a self-administered questionnaire to a sample of members of the American Academy of Pediatrics who lived in Massachusetts. Pediatricians were asked (1) how dangerous they believed fever to be, (2) how they treated fever in their practice, and (3) what types of educational information they gave families regarding fever. One-hundred seventy two of the 234 (74%) eligible pediatricians returned the survey; 151 were completed. Sixty percent of the respondents were male, and 75% practiced some form of primary or episodic care. Ninety-eight (65%) believed that fever itself could be dangerous to a child, with 58 (60%) of the original 98 citing that a temperature of 104 degrees F or greater could lead to complications such as seizures, brain damage, or death. In practice, 108 (72%) always or often recommended treatment to reduce fever and 96 (89%) of the 108 did so at temperatures between 101 degrees and 102 degrees F. One hundred thirty-one (88%) respondents agreed that a sleeping child with fever should be left undisturbed. One hundred twenty-one (80%) pediatricians always or often tried to educate families about fever during sick-child visits, yet only 38% addressed the dangers of fever.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437425 TI - Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study. AB - The implications of low-level lead exposure for children's intellectual and academic performance at school age are uncertain. This issue was investigated in a prospective study of middle-class and upper-middle-class children with low lifetime exposures to lead. A battery of neuropsychological tests was administered at age 10 years to 148 children whose lead exposure and cognitive function had been previously assessed at ages 6, 12, 18, 24, and 57 months. Primary endpoints were Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Kaufman Test of Educational Achievement (K-TEA). Higher levels of blood lead at age 24 months, but not at other ages, were significantly associated with lower global scores on both the WISC-R and the K-TEA after adjustment for potential confounders. Over the range of approximately 0 to 25 micrograms/dL, a 0.48-mumol/L (10 micrograms/dL) increase in blood lead at 24 months was associated with a 5.8-point decline in WISC-R Full-Scale IQ (95% confidence interval: 1.7 to 9.9, P = .007) and an 8.9-point decline in K-TEA Battery Composite score (95% confidence interval: 4.2 to 13.6, P = .0003). Mean blood lead level at age 24 months was 0.31 mumol/L (6.5 micrograms/dL; SD: 4.9, 90% percentile: 12.5). Slightly elevated blood lead levels around the age of 24 months are associated with intellectual and academic performance deficits at age 10 years. PMID- 1437426 TI - Poisoning prevention knowledge and practices of parents after a childhood poisoning incident. AB - This study investigated the effectiveness of a poison center-initiated mailed intervention on improving the preventive practices of families whose preschool child had recently experienced a poisoning incident. A low-cost, mailed poisoning prevention packet consisting of telephone stickers, a +f41 coupon for syrup of ipecac, one slide-style cabinet lock, a nine-step checklist for "poison-proofing" the home, pamphlets, and a cover letter was tested prospectively on a population of parents calling a poison center for advice about possible poisoning exposures involving their preschool children. Parents without ipecac 1 week after the incident were randomized so that half received the mailed intervention. A "blind" follow-up telephone interview was conducted 3 months later. Of the 336 original families enrolled in the study, 301 (90% retention) completed the follow-up interview. Those who had received the intervention were more likely to have a telephone sticker than control families (78% vs 39%; P < .0001) and were more likely to be using at least one slide lock in the home (59% vs 40%; P < .001). However, intervention families were no more likely to have ipecac on hand than control families (57% vs 52%; P = not significant) and did not indicate a higher rate of compliance with suggested changes in other behaviors and practices to prevent poisonings. A poisoning recurrence rate of 3.7% was seen in the total sample during the 3-month period of surveillance; there was no difference between groups in recurrence rate. Even after a poisoning event, parents may not be sufficiently motivated to take poisoning prevention measures on their own.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437428 TI - Pediatric residency training: ten years after the Task Force report. AB - A sample of 3000 pediatricians who had completed their residency training in 1978 or later were surveyed regarding the perception of the adequacy of their residency training in specific aspects of pediatric practice and in a number of subspecialty areas. The survey was almost identical with the one that formed the basis for the American Academy of Pediatrics Task Force on Pediatric Education report in 1978. The results revealed relatively little change in the high rates of perceived "insufficient training" in all the areas of pediatrics described as "underemphasized" in the Task Force report. However, those residents who received their training during the second half of the 10 years since the Task Force survey reported significant improvement in the previously underemphasized areas of developmental and behavioral pediatrics and adolescent medicine. Results also revealed a significant increase in the number of pediatricians who identify either a subspecialty interest or subspecialty practice in developmental or behavioral pediatrics. The increase in pediatric subspecialists and the improved training experience since 1984 indicate that the Task Force report may have had a positive impact on residency training in developmental and behavioral pediatrics. PMID- 1437427 TI - Improving influenza vaccination rates in children with asthma: a test of a computerized reminder system and an analysis of factors predicting vaccination compliance. AB - Fewer than 10% of children with moderate or severe asthma receive an annual influenza vaccination despite their heightened susceptibility to severe infections and recommendations by the American Academy of Pediatrics and the Immunization Practices Advisory Committee that all such children be vaccinated annually. Patient, provider, and system factors leading to this poor vaccination rate are not well understood. This study tested the effectiveness of a computerized reminder system in improving influenza vaccination rates in children with asthma and examined patient barriers to vaccination at one pediatric clinic in an urban teaching hospital. A computer database identified 124 children with moderate or severe asthma. Patients were randomly assigned either to study group (n = 63), who were sent a personalized letter reminder about the need for an influenza vaccination, or to a control group (n = 61), who received no reminder. Study group mothers were interviewed 2 months after the letter was sent to assess factors associated with receipt of vaccination, including demographic features, parental worry about asthma and vaccine side effects, the four dimensions of the Health Belief Model, and health locus of control beliefs. Nineteen study group patients (30%) received an influenza vaccination, compared with only 4 control patients (7%) (P < .01). Forty-three mothers of children in the study group were interviewed; 14 (33%) of these children had received the vaccination. Of the characteristics investigated, two significantly correlated with vaccination compliance: high levels of parental worry about asthma (positively correlated: odds ratio = 23.3, P < .01) and high levels of parental worry about vaccine side effects (negatively correlated: odds ratio = 0.087, P = .025).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437429 TI - Relationship of intraventricular hemorrhage or death with the level of umbilical artery catheter placement: a multicenter randomized clinical trial. Umbilical Artery Catheter Trial Study Group. AB - Umbilical artery catheters are frequently used in the care of very low birth weight neonates to monitor arterial blood gas values. Historically, catheters with the tip placed low, in the abdominal aorta, have been associated with an increased risk of peripheral vascular complications. Recently, a report suggested that catheters placed high, in the thoracic aorta, were associated with an increased risk of intraventricular hemorrhage. To determine whether there is an association between the placement of an umbilical artery catheter high, in the thoracic aorta, and the occurrence of intraventricular hemorrhage (grades II through IV) or death within the first 5 days of life, a multicenter randomized trial was conducted. Nine hundred seventy neonates weighing 500 through 1499 g were randomly assigned to receive either high catheters, in the thoracic aorta closest to the sixth to eight thoracic vertebra, or low catheters, in the abdominal aorta closest to the third to fifth lumbar vertebra. The incidence of the primary outcome (intraventricular hemorrhage grades II through IV and/or death) was 25.8% among newborns with high catheters and 23.1% in those with low catheters (relative risk = 1.12, 95% confidence interval = 0.89, 1.39). However, a significant interaction was observed between the level of catheter placement and birth weight for neonates weighing 750 through 999 g and those weighing 1000 through 1499 g. The subgroup of neonates weighing 750 to 1000 g had a relative risk of the primary outcome of 0.72 (95% confidence interval = 0.49, 1.07), while those weighing 1000 through 1499 g had a relative risk of 2.02 (1.21, 2.36).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437430 TI - Excess morbidity associated with interhospital transport. AB - A prospective study was performed to determine whether excess morbidity occurred in critically ill and injured pediatric patients during interhospital transport compared with morbidity in a control group. Control observations were made during the first 2 hours of pediatric intensive care unit (PICU) care of patients emergently admitted from within the same institution and not requiring interhospital transport. The first 2 PICU hours of control patients corresponded to the interval of transport in those who required interhospital transfer. Transport care was provided by nonspecialized teams from referring hospitals. Morbidity occurred in 20.9% of 177 transported patients, exceeding the morbidity rate of 11.3% in 195 control patients (P < .05). The difference in morbidity was due to intensive care-related adverse events (eg, plugged or dislodged endotracheal tubes, loss of intravenous access) in 15.3% and 3.6% of transported and control patients, respectively (P < .05). Physiologic deterioration occurred at similar rates of 7.9% and 8.7% in transported and control patients, respectively (P > .05). Slightly greater pre-ICU severity of illness in transported than control patients (median Pediatric Risk of Mortality Score = 10 and 7, respectively, P < .05) and greater pre-ICU therapy relative to severity (P < .05) in control patients are potential confounding sources of the morbidity differences. If patients are stratified into subgroups of similar pre-ICU severity, an excess of intensive care-related adverse events in transported patients remains evident in the severe subgroup (P < .05). Further investigation is warranted to determine whether specialized transport teams can reduce the excess morbidity associated with interhospital transport of critically ill and injured pediatric patients. PMID- 1437431 TI - Persistent pulmonary hypertension in premature neonates with severe respiratory distress syndrome. AB - Cardiac catheterization studies have demonstrated that Doppler-derived flow velocities in the ductal flow jet and the left pulmonary artery accurately predict the aortopulmonary pressure difference and left-to-right shunt size in newborns. To assess the presence of persistent pulmonary hypertension in premature newborns with various degrees of respiratory distress syndrome (RDS) severity, we estimated pulmonary artery pressure from the aortopulmonary pressure difference and pulmonary blood flow from the left pulmonary artery flow velocity with color-flow-directed, pulsed Doppler echocardiography. Seventy-nine premature neonates were divided into three groups--no or mild RDS (n = 27), severe RDS (n = 38), and fatal RDS (n = 14)--and compared with a group of healthy term neonates (n = 34). In premature and term neonates with no/mild RDS the mean +/- SEM aortopulmonary pressure difference increased from 7.3 +/- 0.4 and 6.6 +/- 0.5 mm Hg to 22.8 +/- 1.4 and 21.4 +/- 1.1 mm Hg over the first 24 hours (P < .001). The mean aortopulmonary pressure difference was 0.9 +/- 0.3 mm Hg during the first 72 hours in neonates with fatal RDS, but increased from 1.5 +/- 0.3 mm Hg at 4 hours to 7.4 +/- 0.6 at 24 hours and 21.5 +/- 0.7 mm Hg at 72 hours of age in neonates with severe RDS. Left pulmonary artery velocity time integrals were 18.3 +/- 0.5 cm in premature and 18.8 +/- 0.5 cm in term neonates with no/mild RDS at 12 hours vs 11.2 +/- 0.4 cm in neonates with severe and 9.9 +/- 0.5 cm in neonates with fatal RDS (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437432 TI - Relationship of sudden infant death syndrome to maternal smoking during and after pregnancy. AB - Sudden infant death syndrome (SIDS) is associated with maternal smoking during pregnancy. However, the relationship between tobacco exposure during infancy and SIDS is unknown. The examination of infants whose mothers smoked only after pregnancy will help determine the relationship between passive cigarette exposure during infancy and SIDS risk. This case-control analysis used data on normal birth weight (> or = 2500 g) infants included in the National Maternal and Infant Health Survey, a nationally representative sample of approximately 10,000 births and 6000 infant deaths. Infants were assigned to one of three exposure groups: maternal smoking during both pregnancy and infancy (combined exposure), maternal smoking only during infancy (passive exposure), and no maternal smoking. SIDS death was determined from death certificate coding. Logistic regression was used to adjust for potentially confounding variables. Infants who died of SIDS were more likely to be exposed to maternal cigarette smoke than were surviving infants. Among black infants the odds ratio was 2.4 for passive exposure and 2.9 for combined exposure. Among white infants the odds ratio was 2.2 for passive exposure and 4.1 for combined exposure. After adjustment for demographic risk factors, the odds ratio for SIDS among normal birth weight infants was approximately 2 for passive exposure and 3 for combined exposure for both races. These data suggest that both intrauterine and passive tobacco exposure are associated with an increased risk of SIDS and are further inducement to encourage smoking cessation among pregnant women and families with children. PMID- 1437433 TI - Pediatric submersions: prehospital predictors of outcome. AB - This retrospective cohort study was conducted to test prehospital prognostic indicators in pediatric submersion victims. The authors studied all less than 20 years old victims submerged in the non-icy waters of King County, WA who were treated by Seattle or King County Emergency Medical Services between 1985 and 1989 and were hospitalized or died. Seventy-seven victims were identified from emergency medical services incident logs, hospital discharge records, and medical examiner's registries. Outcome predictors were correlated with the victim's condition at hospital discharge. Of 29 victims in cardiac arrest, 13 had return of spontaneous circulation following field resuscitation. Of these, 6 (21%) survived, with mild (n = 2) and severe (n = 4) neurologic impairment at hospital discharge. The best outcome predictors were obtained in the field. These were, for death or severe neurologic impairment, submersion durations > 10 minutes (6/6) and resuscitation durations > 25 minutes (17/17), and for good outcome, sinus rhythm (37/37), reactive pupils (43/43), and neurologic responsiveness (40/40) at the scene. Field-determined factors were reproducibly good outcome predictors. Aggressive emergency medical services may save the lives of pediatric victims in cardiac arrest following short submersion durations. The data support pronouncing dead in the field those pediatric victims of non-icy submersions who do not respond to advanced life support within 25 minutes. PMID- 1437434 TI - Outlook for the child with a cephalocele. AB - Specific information on the outcome for a child with a cephalocele can be difficult to find and interpret. To update outcome information for the child with a cephalocele, the investigators compared outcome of 34 infants from their institution with that of those in previously published series. For the infants from the investigators' institution, overall mortality was 29% and was confined to infants with posterior defects, which was consistent with other published series. Additional major congenital abnormalities were present in nearly half the infants, and these were an important factor in contributing to a poorer prognosis as well as whether the defect could be operatively reduced. Seizures and hydrocephalus were often secondary problems in those infants who did worse. In addressing outlook for the infant with the cephalocele, primary factors to be considered are operability and the presence of additional major abnormalities, both intracranial and extracranial. PMID- 1437435 TI - Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis. AB - Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of "nonresponders" and "clear responders" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437436 TI - Systemic infections due to Streptococcus pneumoniae relatively resistant to penicillin in a children's hospital: clinical management and outcome. AB - Streptococcus pneumoniae isolates relatively (0.1 microgram/mL < minimum inhibitory concentration < or = 1.0 microgram/mL) resistant to penicillin (RRP) have been recovered worldwide, but reports of therapy and outcome of systemic infections due to these strains are limited. This retrospective study of prospectively identified patients reviews the clinical features, management, and outcome of 19 children with systemic infections due to S pneumoniae. From January 1, 1989 to December 31, 1991, 13 of 244 blood (5.3%) and 4 of 32 cerebrospinal fluid (12.5%) pneumococcal isolates were relatively resistant to penicillin. The serotypes were as follows: 14 (12 isolates), 6 (4 isolates), 19 (2 isolates), 23 (1 isolates). One peritoneal fluid isolate and one joint fluid isolate were also relatively resistant to penicillin. The mean age of the 19 patients was 30 months (range 5 to 104 months), and five children had underlying disorders. Eleven children (nine inpatients) were treated initially with a parenteral cephalosporin. Six patients were treated as outpatients, and all had (occult) bacteremia. Three of these patients received ceftriaxone intramuscularly in the emergency department; five were treated with amoxicillin/clavulanic acid, and one received amoxicillin. Seven of 13 children treated in the hospital became afebrile in 48 hours. Three others were afebrile from the time of admission. Repeat blood cultures obtained within 24 to 48 hours after therapy was initiated were sterile in 10 children. All but one child responded to initial therapy. The recovery of S pneumoniae isolates relatively resistant to penicillin has increased in our hospital during the last 3 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437437 TI - Milk production by mothers of premature infants: influence of cigarette smoking. AB - The volume of milk produced by mothers who smoked cigarettes (n = 11) and control subjects who did not smoke (n = 29) was compared after the delivery of their preterm infants (28 to 32 weeks gestation). Milk production was significantly less among those who smoked, with or without adjusting for age, race, parity, gravidity, weight-for-height, prior nursing experience, customary alcohol and caffeine intake, infant birth weight, and pumping frequency. Each mother maintained her milk production using an electrical breast pump and without the stimulus of her infant suckling at the breast. Daily frequency and duration of breast pump usage were similar in the two groups. At 2 weeks postpartum, 24-hour milk volumes were 406 +/- 262 mL for mothers who smoked and 514 +/- 338 mL for control subjects. Between 2 to 4 weeks postpartum, the mean change in 24-hour milk volume (milliliters per 24 hours) of control subjects increased (+113 +/- 179 mL, P < .005), whereas milk volume of mothers who smoked cigarettes remained unchanged (-47 +/- 122 mL, P = .25). The percentage change in milk volume between 2 and 4 weeks for the combined groups was significantly related to four factors: pumping frequency, change in daily pumping frequency, day of initiation of pumping, and smoking status. Total and protein nitrogen, lactose, calcium, and phosphorous concentrations did not differ in milks from mothers who smoked cigarettes and mothers who did not smoke.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437438 TI - School functioning of US children with asthma. AB - Data from the 1988 US National Health Interview Survey on Child Health, a nationally representative cross-sectional survey, were used to determine national estimates of school outcomes (grade failure, learning disabilities, and suspension/expulsion) and mean number of absences for children with asthma (CWA) compared to well children without current health conditions. Families indicated that 536 (4.9%) of the 10,362 survey children in grades 1 through 12 had had asthma in the previous 12 months. Families reported 18% of CWA vs 15% of well children had grade failure, 9% of CWA vs 5% of well children had learning disabilities, and 5% of CWA vs 6% of well children had been expelled or suspended. Children with asthma averaged 7.6 school days absent compared with 2.5 days for the well group. Multiple logistic regression was used to compare the odds of grade failure, learning disabilities, and suspension/expulsion among CWA and well children, overall and stratified by income. Similar methods were used to assess the role of health status among asthmatic children. After adjustment for demographic factors, CWA had similar risks of grade failure and suspension/expulsion, but 1.7 times the risk of learning disability compared with well children. Also, among families with incomes below $20,000, CWA had twice the odds of grade failure compared with well children. For asthmatic children, reported health status was an important predictor of learning disability. Ten percent of CWA were reported to be in fair-poor health. After adjustment for demographic factors, those in fair-poor health were twice as likely to have a reported learning disability compared with those in good-excellent health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437439 TI - Detection of IgM rheumatoid factors by enzyme-linked immunosorbent assay in children with juvenile rheumatoid arthritis: correlation with articular disease and laboratory abnormalities. AB - This study was undertaken to determine the clinical relevance of IgM rheumatoid factors (RFs) detected by enzyme-linked immunosorbent assay (ELISA) in children with juvenile rheumatoid arthritis (JRA) by examining their association with severity of acute articular disease. ELISAs for IgM-RF were performed on serum specimens from 65 children with JRA. Activity of articular disease was estimated by an arbitrary scoring system. Significant differences were seen in articular disease activity between the group of children with polyarticular disease who were IgM-RF-positive by ELISA compared with those who were IgM-RF-negative (P = .0003). When a small group of individual children with polyarticular disease were followed longitudinally, similar correlations were found between severity of acute disease and the presence of IgM-RFs detected by ELISA. In children with pauciarticular JRA, expression of IgM-RFs appeared to be a transient phenomenon with no correlation with either articular disease or laboratory abnormalities. PMID- 1437440 TI - Epidemiology of juvenile chronic arthritis in southwestern Sweden: a 5-year prospective population study. AB - Previous epidemiological studies of juvenile chronic arthritis (JCA) report divergent results owing to differences in diagnostic criteria, patient retrieval, and study designs. To investigate incidence and prevalence of JCA in a total population, this prospective survey was performed in southwestern Sweden between 1984 and 1988. Cases were identified using the European League Against Rheumatism criteria for JCA and were reported annually from eight pediatric departments and local pediatricians in the studied area. During the 5 years, 213 new cases of JCA were found, corresponding to an incidence of 54.6 per 100,000 children younger than 16 years of age. The average annual incidence was 10.9 per 100,000. The peak incidence rate, 18.3 per 100,000 was found in girls 0 through 3 years old. The lowest incidence rate, 6.4 per 100,000, was found among boys 12 through 15 years old. In December 1988, 334 cases of JCA were recorded, giving a prevalence of 86.3 per 100,000. When patients in remission were omitted the prevalence was 64.1 per 100,000. The monoarticular+pauciarticular onset type constituted 68.3% of the prevalence cases, while 21.9 were polyarticular and 6.6% had systemic onset. To avoid underestimation of incidence and prevalence, and to get a correct picture of disease patterns, epidemiological surveys of JCA should be population-based rather than referral center-based. Further descriptive studies of JCA in different well-defined geographic areas are important to make valid comparisons. Such comparisons could give clues to etiological factors, both genetic and environmental. PMID- 1437441 TI - Database use in neonatal intensive care units: success or failure. AB - The purpose of this national survey was to define the extent and features of database use by 445 tertiary level neonatal intensive care nurseries in the United States. Of the 305 centers responding to our survey, 78% had a database in use in 1989 and 15% planned to develop one in the future. Nurseries varied remarkably in the volume of data collected, the amount of time devoted to completing data collection forms, and the personnel involved in data collection. Although data were used primarily for statistical reports (93% of nurseries), quality assurance (73%) and research activities (61%) were also enhanced by database information. Neonatal databases were used to generate reports for the permanent medical record in 38% of centers. Satisfaction with the database was dependent on how useful the database information was to centers which collected and actually used a large volume of information. Overall, nurseries expressed a high degree of confidence in the data they collected, and 65% felt their neonatal database information could be used directly in publication of research. It was disturbing that accuracy of data was not monitored formally by the majority of nurseries. Only 27% of centers followed a routine schedule of data quality assurance, and only 53% had built in error messages for data entry. We caution all who receive database information in the form of morbidity and mortality statistics, clinical reports on patients cared for in neonatal units, and published manuscripts to be attentive to the quality of the data they consume. We feel that future database design efforts need to better address data quality control. Our findings stress the importance and need for immediate efforts to better address database quality control. PMID- 1437442 TI - Pyogenic granulomas of infancy masquerading as strawberry hemangiomas. PMID- 1437443 TI - Tocopherol levels in infants < or = 1000 grams receiving MVI pediatric. PMID- 1437444 TI - Even advantaged children show cognitive deficits from low-level lead toxicity. PMID- 1437445 TI - How much resuscitation is enough resuscitation? PMID- 1437446 TI - Pediatrics and the Patient Self-Determination Act. PMID- 1437447 TI - Is science good for the soul? PMID- 1437448 TI - Stimulus mislocalization depends on spatial frequency. AB - It was previously reported that briefly presented peripheral stimuli are perceived closer to fixation than continuously presented stimuli at the same eccentricity; this effect has, however, not proved consistently replicable. In this study it was investigated whether the misperception of location might depend upon the spatial frequency content of the stimulus. Spatial-frequency-filtered vertical bars were displayed briefly and their locations were judged relative to continuously visible comparison spots. For monocular stimuli, a significant foveopetal mislocalization of the bar was obtained that increased in size as spatial frequency was lowered. Even larger mislocalizations were obtained for dichoptically presented horizontally disparate pairs of bars, and this effect also increased at low spatial frequencies. Possible underlying mechanisms are discussed, and spatial frequency is suggested to have been the confounding factor in previous studies. PMID- 1437449 TI - Asymmetric interactions in the processing of the visual dimensions of position, width, and contrast of bar stimuli. AB - The processing of different dimensions of a single stimulus may be either integral or separable. Dimensions are called integral if correlated variation of one improves discrimination on the basis of the other and random variation of one interferes with discrimination on the basis of the other. For separable dimensions on the other hand, subjects can attend to one dimension and disregard variations in the other. These discrimination tests were used to find the interactions between the processing of the visual dimensions of position, width, and contrast of a light bar stimulus. The relations between these dimensions were found to be asymmetric: judgments of position and width are independent of contrast variations, but variations in these dimensions influence contrast discriminations. Furthermore, position variations influence width judgements more than vice versa. The data were analyzed for repetition effects, and it was found that this model is not sufficient to explain all the interaction phenomena. The asymmetries found may be related to the different ways these dimensions are mapped onto cortical neuron responses. PMID- 1437450 TI - Neon flank and illusory contour: interaction between the two processes leads to color filling-in. AB - Two aspects of neon color spreading, local color spreading (neon flank) and illusory contour, were investigated by dichoptic viewing. Neon flank was not observed under appropriate dichoptic stimulation, suggesting that input to the process for local color spreading is based on monocular configuration. However, illusory contours were formed according to the interocularly combined configuration rather than according to each monocular configuration, suggesting that input to the process responsible for illusory contours should be ocularly nonselective and binocular, rather than monocular. The possibilities of artifacts such as those arising from interocular rivalry were appropriately eliminated, and thus, it is tentatively concluded that the process underlying local color spreading is monocularly driven, whereas the process underlying illusory contours is binocularly driven. Furthermore, a new demonstration is presented that indicates that interocularly-induced illusory contours 'capture' and extend the monocularly-induced local color spreading, resulting in global color spreading (neon color spreading). These results support our hypotheses that neon color spreading involves two separable processes in the early visual processing, the feature detection process (for local color spreading) and the illusory contour process, and that these two processes interact with each other at later stages of cortical processing. The relation of local color spreading and illusory contours to surface separation is also discussed. PMID- 1437451 TI - Amodal completion, depth stratification, and illusory figures: a test of Kanizsa's explanation. AB - Subjective contours have been explained by Kanizsa as being a consequence of amodal completion of incomplete figures. According to the theory of amodal completion, figural incompleteness triggers the emergence of an illusory object superimposed on the gaps in the inducers, which in turn hide parts of the pattern, thus suggesting that the plane of the illusory object must always be seen to be above the plane of the inducers. A figure was created in which subjective contours are seen despite the fact that the perceived depth relationships run counter to that required by the theory of amodal completion. In four experiments, this depth relationship is confirmed by using direct and indirect measures which assess both registered and apprehended depth. By emphasizing a logical inconsistency in the explanation based on amodal completion, the results show that amodal completion, at least in Kanizsa-like patterns, cannot be considered as a causal factor for subjective contour figures. PMID- 1437452 TI - Linear vection in the central visual field facilitated by kinetic depth cues. AB - Illusory self-motion (vection) is thought to be determined by motion in the peripheral visual field, whereas stimulation of more central retinal areas results in object-motion perception. Recent data suggest that vection can be produced by stimulation of the central visual field provided it is configured as a more distant surface. In this study vection strength (tracking speed, onset latency, and the percentage of trials where vection was experienced) and the direction of self-motion produced by displays moving in the central visual field were investigated. Apparent depth, introduced by using kinetic occlusion information, influenced vection strength. Central displays perceived to be in the background elicited stronger vection than identical displays appearing in the foreground. Further, increasing the eccentricity of these displays from the central retina diminished vection strength. If the central and peripheral displays were moved in opposite directions, vection strength was unaffected, and the direction of vection was determined by motion of the central display on almost half of the trials when the centre was far. Near centres produced fewer centre-consistent responses. A complete understanding of linear vection requires that factors such as display size, retinal locus, and apparent depth plane are considered. PMID- 1437453 TI - Orientation selectivity in infancy: behavioural evidence for temporal sensitivity. AB - One-month-old infants were tested with a habituation-recovery paradigm to determine whether they could discriminate phase-shifting grating patterns that switched between two orientations, three or eight times a second, from grating patterns that only shifted in phase. The infants were found to discriminate patterns switching orientation at the lower temporal rate of 3 reversals s-1, but not 8 reversals s-1. This finding supports the idea that orientation-selective mechanisms improve in their temporal sensitivity during early infancy. Where they can be compared, the results from behavioural and electrophysiological studies agree as to the course of this development. PMID- 1437454 TI - Gaze angle explanations of the induced effect. AB - Mayhew and Longuet-Higgins formulated a computational explanation of the induced effect which successfully predicts the conditions under which the induced effect will occur. Underlying their theories are the assumptions that disparity information is separated into horizontal and vertical components and that the vertical disparities are used to calculate the gaze angles. An implementation of the fusional explanation introduced by Petrov makes similar predictions for the induced effect, but does not depend on these two assumptions. PMID- 1437455 TI - The effect of defocusing the image on the perception of the temporal order of flashing lights. AB - The temporal interval between flashing lights that is required to perceive nonsimultaneity decreases as the refractive error increases from 0 to +2 diopters. The interval then remains constant with further increases to 3 and 4 diopters. The results are discussed in terms of the relative increase of transient to sustained visual channels and of the increase in apparent movement. PMID- 1437456 TI - Recognising faces: effects of lighting direction, inversion, and brightness reversal. AB - When information about three-dimensional shape obtained from shading and shadows is ambiguous, the visual system favours an interpretation of surface geometry which is consistent with illumination from above. If pictures of top-lit faces are rotated the resulting stimulus is both figurally inverted and illuminated from below. In this study the question of whether the effects of figural inversion and lighting orientation on face recognition are independent or interactive is addressed. Although there was a clear inversion effect for faces illuminated from the front and above, the inversion effect was found to be reduced or eliminated for faces illuminated from below. A strong inversion effect for photographic negatives was also found but in this case the effect was not dependent on the direction of illumination. These findings are interpreted as evidence to suggest that lighting faces from below disrupts the formation of surface-based representations of facial shape. PMID- 1437457 TI - A case of a dual frame of reference. AB - It is demonstrated that observers may relate to two parts of the same object by using two different frames of reference. Subjects were asked to indicate directions within a model of a hallway in which signs were posted on a single prism. The majority of subjects interpreted a sign frontally facing them as indicating the direction which is ahead of them, yet they interpreted an adjacent sign that was slanted with respect to the frontal plane as indicating a direction which is at the same side of the line of sight as the sign is. This manifests a mixture of an egocentric and an object-centred frame of reference, that is reminiscent of the mixture of local spatial interpretations in impossible pictures. It is suggested that frames of reference are not necessarily unique in a given percept, and that they are not derived from a global computation. PMID- 1437458 TI - Sighting-down and the Poggendorff illusion: a mystery within a mystery. AB - As reported before, sighting-down one of the diagonal lines on a typical Poggendorff pattern will reduce the illusion even if that situation is only pictorial. But here it is also argued that sighting-down itself requires further understanding. PMID- 1437459 TI - The first pictures: perceptual foundations of Paleolithic art. AB - Paleolithic representational art has a number of consistent characteristics: the subjects are almost always animals, depicted without scenic background, usually in profile, and mostly in outline; the means of representation are extremely economical, often consisting of only a few strokes that indicate the salient features of the animal which are sufficient to suggest the whole form; and it is naturalistic to a degree, but lacks anything like photographic realism. Two elementary questions are raised in this essay: (i) why did the earliest known attempts at depiction have just these characteristics and not others? and (ii) how are objects so minimally represented recognizable? The answers seem to lie with certain fundamental features of visual perception, especially figure-ground distinction, Gestalt principles of closure and good continuation, line surrogacy, component feature analysis, and canonical imaging. In the earliest pictures the graphic means used are such that they evoke the same visual responses as those involved in the perception of real-world forms, but eschew redundancies of color, texture, linear perspective, and completeness of representation. PMID- 1437460 TI - Spectral content as a cue to perceived auditory distance. AB - Changes in the spectral content of wide-band auditory stimuli have been repeatedly implicated as a possible cue to the distance of a sound source. Few of the previous studies of this factor, however, have considered whether the cue provided by spectral content serves as an absolute or a relative cue. That is, can differences in spectral content indicate systematic differences in distance even on their first presentation to a listener, or must the listener be able to compare sounds with one another in order to perceive some change in their distances? An attempt to answer this question and simultaneously to evaluate the possibly confounding influence of changes in the sound level and/or the loudness of the stimuli are described in this paper. The results indicate that a decrease in high-frequency content (as might physically be produced by passage through a greater amount of air) can lead to increases in perceived auditory distance, but only when compared with similar sounds having a somewhat different high-frequency content, ie spectral information can serve as a relative cue for auditory distance, independent of changes in overall sound level. PMID- 1437461 TI - Traffic lights. PMID- 1437462 TI - Perspective, orientation disparity, and anisotropy in stereoscopic slant perception. AB - Stereoscopic depth estimates are not predictable from the geometry of point disparities. The configural properties of surfaces (surface contours) may play an important role in determining, for example, slant responses to a disparity gradient, and the marked anisotropy in favour of slant around a horizontal axis. It has been argued that variation in slant magnitude are attributable to the degree of perspective conflict present and that anisotropy is attributable to orientation disparity, which varies with the axis of slant. Three experiments were conducted in which configural properties were varied to try and tease apart the respective roles of orientation disparity and conflicting perspective in determining stereoscopic slant perception and slant axis anisotropy. The results could not be accounted for by the magnitude of the orientation disparities present. Conflicting perspective cues appeared to play a role but only for slant around a vertical axis. It was concluded that there are important configural effects in stereopsis attributable neither to orientation disparity nor to perspective. PMID- 1437463 TI - Convergent and divergent perspective. AB - Use of divergent (or inverse) perspective in pictures is often regarded as arbitrary or even as erroneous in spite of the fact that entire schools of art exist in which this kind of perspective is regularly used. An experiment is reported which shows that a significant trend towards divergent perspective is experienced by subjects viewing laterally displaced three-dimensional arrays. Centrally viewed arrays show the expected perceptual convergence. It is therefore argued that divergent perspective, under appropriate conditions, is as perceptually legitimate an experience as convergent perspective. PMID- 1437464 TI - Spatial gating effects on judged motion of gratings in apertures. AB - Wallach has described in qualitative terms the movement of lines behind apertures. We related the data he obtained to the aperture problem, constructed a model of movement perception, and carried out tests of the model. Experiment 1 was a parametric study, and showed the conditions under which a reliable illusion (the barber pole illusion) of diagonal movement of lines along an aperture could be obtained, and when fluctuating judgements or veridical percepts were obtained. On the basis of this study a dipole model was constructed. The model was further developed and tested. In experiment 2 the effects of total area of stimulation were examined: diagonal gratings were viewed behind multiple apertures. In experiment 3 the effects of local signs were examined: diagonal gratings were viewed in an aperture which had edges cut in small steps and stairs, with the risers parallel to the grating, and the treads parallel to the direction of motion of the grating. Experiment 4 was designed to test a prediction about the motion aftereffect of dots near and far from the point of fixation, and the results confirmed the model. It was concluded that the model accounts for the barber pole illusion and, generally, for the movement of gratings in apertures. PMID- 1437465 TI - Curvature is a basic feature for visual search tasks. AB - A curved target can be found efficiently among straight distractors in a visual search task. This could reflect the status of curvature as a basic feature for visual search. Alternatively, curvature could be detected as a locus of high variation in orientation. In a series of experiments it is shown that efficient search for curvature is possible even if local variation in orientation is eliminated as a cue. This suggests that curvature is part of the set of basic features for visual search and that this set is derived relatively late in the course of visual processing. PMID- 1437466 TI - Seeing lumps, sticks, and slabs in silhouettes. AB - Marr has suggested that we see three-dimensional (3-D) shapes in silhouettes because we make the implicit assumption that the viewed shapes are generalized cones. One difficulty with this suggestion is that it cannot deal with silhouettes of irregular 3-D shapes like clouds and trees; another is that it only applies to generalized cones with a relatively high length:width ratio. An alternative explanation, suggested by evidence from cross-cultural studies of language, from children's early speech, and from children's early drawings, is that the scene primitives actually used by humans are not generalized cones but 'lumps', 'sticks', and 'slabs', that is, primitives whose only shape properties are their relative extensions in 3-D space. In this paper it is proposed that the implicit assumption we make in interpreting silhouettes is that the extendedness of the silhouette reflects the extendedness of the viewed shape, so that a round region is seen as a lump and a long region is seen as a stick; and that such views seem "natural" because they are the views most likely to be encountered in normal environments. This account is more general than that of Marr because it explains how we interpret silhouettes of all kinds of 3-D shapes, even very irregular ones. Unlike Marr's account, it also deals with flat shapes like slabs and discs, and shows why it is difficult to see these shapes in silhouettes. PMID- 1437467 TI - Use of preferential inspection to define the viewing sphere and characteristic views of an arbitrary machined tool part. AB - Measurements were made of the way human subjects visually inspected an idealized machined tool part (a 'widget') while learning the three-dimensional shape of the object. Subjects were free to rotate the object about any axis. Inspection was not evenly distributed across all views. Subjects focused on views where the faces of the object were orthogonal to the line of sight and the edges of the object were aligned parallel or at right angles to the gravitational axis. These 'face' or 'plan' views were also the easiest for subjects to bring to mind in a mental imagery task. By contrast, when subjects were instructed to imagine the views displaying the most structural information they visualized views lying midway between face views. PMID- 1437468 TI - Serial pattern complexity: irregularity and hierarchy. AB - In perception research, various models have been designed for the encoding of, for example, visual patterns, in order to predict the human interpretation of such patterns. Each of these encoding models provides a few coding rules to obtain codes for a pattern, each code expressing regularity and hierarchy in that pattern. Some of these models employ the minimum principle which states that the human interpretation of a pattern is reflected by the simplest code for that pattern, ie the simplest code according to a given complexity metric. In this paper a new complexity metric is proposed. This metric is based on a formal analysis of the concept of regularity. Some conclusions of this analysis are sketched. The new metric does not depend on artifacts of the coding rules. It accounts for the amounts of irregularity and hierarchy as represented in a code of a pattern, such that these two amounts can be added to determine the complexity of a code. An experiment is discussed that shows that the new metric performs significantly better than the metrics used previously. In particular, the new metric predicts more local pattern organizations than the old metrics. This implies that various local pattern organizations do not falsify the minimum principle anymore. PMID- 1437469 TI - Attention and interference in prospective and retrospective timing. AB - Subjects listened to a series of musical selections and then judged the duration of each selection. Some subjects were informed beforehand that timing was involved (prospective timing) whereas others were informed afterwards (retrospective timing). Half the groups performed a concurrent proofreading task during stimulus presentation. The results showed a trade-off between temporal and nontemporal task performance: prospective-timing groups were more accurate in judging time and were worse at proofreading, whereas retrospective-timing groups were relatively poor at judging time but better at proofreading. This pattern is consistent with Michon's notion of an essential equivalence between temporal and nontemporal processing, and supports the predictions of an attentional allocation model of timing. The proofreading task interfered both with prospective and with retrospective timing, and both types of time judgments were influenced in the same way by effects of stimulus context. These results imply that similar timing processes operate under prospective and retrospective conditions. PMID- 1437470 TI - Feature analysis and the role of similarity in preattentive vision. AB - Texture arrays of line elements at various orientations were used to study three phenomena of preattentive vision. Subjects were asked (1) to discriminate texture areas and to distinguish their form (experiments on texture segmentation); (2) to detect salient or vertical line elements (experiments on pop-out); and (3) to identify configurations of similar or or dissimilar targets (experiments on grouping). Within the patterns, line orientation was systematically varied to distinguish the effect of differences between areas from the effect of similarity within areas. In all of the experiments, performance was found to depend on local orientation contrast at texture borders rather than on the analysis of line orientation itself. Texture areas were correctly identified only when the orientation contrast at the border well exceeded the overall variation of line orientation in the pattern. Similarly, only target elements with high local orientation contrast were detected fast and "in parallel". Targets with an orientation contrast lower than background variation required serial search. Preattentive grouping was found to depend on saliency, as defined by local orientation contrast, but not on the similarity of line elements. In addition to local orientation contrast, which played an important role in all of the visual phenomena studied, influences from the alignment of line elements with the outline of a figure were also seen. PMID- 1437471 TI - The effects of experimental variables on the perception of American English /r/ and /l/ by Japanese listeners. AB - The effects of variations in response categories, subjects' perception of natural speech, and stimulus range on the identification of American English /r/ and /l/ by native speakers of Japanese were investigated. Three experiments using a synthesized /rait/-/lait/ series showed that all these variables affected identification and discrimination performance by Japanese subjects. Furthermore, some of the perceptual characteristics of /r/ and /l/ for Japanese listeners were clarified: (1) Japanese listeners identified some of the stimuli of the series as /w/. (2) A positive correlation between the perception of synthesized stimuli and naturally spoken stimuli was found. Japanese listeners who were able to easily identify naturally spoken stimuli perceived the synthetic series categorically but still perceived a /w/ category on the series. (3) The stimulus range showed a striking effect on identification consistency; identification of /r/ and /l/ was strongly affected by the stimulus range, the /w/ identification less so. This indicates that Japanese listeners tend to make relative judgments between /r/ and /l/. PMID- 1437472 TI - On the relation between auditory spatial attention and auditory perceptual asymmetries. AB - Laterality investigators have typically interpreted any perceptual asymmetry as a direct expression of the functional organization of the brain. However, many other confounding factors, including the asymmetric distribution of attention, may also contribute to either the magnitude or the direction of any of these advantages. In two experiments, attention was manipulated in a dichotic listening paradigm by presenting a preexposural tone cue to the ear from which the subject was required to report. The time available to orient attention was manipulated by varying the time period between the onset of the cue and the onset of the trial (stimulus onset asynchrony, or SOA). Results indicated that a right ear advantage for the identification of verbal material obtained at a 150-msec SOA was almost completely eliminated at an SOA of 450 msec. In addition, the direction of the ear advantage for emotion identification was found to depend on task difficulty. A left ear advantage, apparent when task difficulty was minimal, was reversed to a right ear advantage when difficulty was increased. These data are taken as evidence that, when subjects are faced with a difficult dichotic task, there is a general tendency for right-handed subjects to bias their attention toward the right ear. Such a tendency is shown not only to have likely seriously compromised the results of past investigations of functional perceptual asymmetries but also to be inconsistent with previously proposed theories of dichotic listening performance. PMID- 1437473 TI - Coherence and transparency of moving plaids composed of Fourier and non-Fourier gratings. AB - We examined the perceptual coherence of two-component moving plaids. The gratings that constituted the plaids were either standard Fourier gratings (F), in which luminance was determined by a drifting sinusoid, or non-Fourier gratings (NF), in which the contrast of a random background was modulated by a drifting sinusoid. These NF gratings are examples of stimuli that generate a compelling percept of motion, even though they fail to elicit a motion signal from motion analyzers based on standard cross-correlation (Chubb & Sperling, 1988). Naive observers viewed three types of stimuli consisting of superpositions of these two components: (1) two standard drifting gratings (F/F), (2) two non-Fourier drifting gratings (NF/NF), and (3) one standard and one non-Fourier drifting grating (F/NF). As expected, the F/F stimulus yielded a compelling percept of coherent motion. The dominant percept of all the observers for the NF/NF stimulus was one of coherent motion, provided that both gratings were visible and of approximately equal contrast. None of the observers reported a dominant percept of coherent motion for the F/NF condition, over a wide range of contrasts for the two grating components and across two varieties of NF gratings. In view of the results of Albright (1992) and Albright and Chaudhuri (1989), that show that single cells in macaque V1 and MT respond to both F and NF motion, one cannot interpret our findings as evidence that F and NF motion are processed independently. Alternative, "higher level" interpretations based on the intrinsically ambiguous nature of the stimuli and physical laws governing the appearance of transparent objects are discussed. PMID- 1437475 TI - Information tradeoffs in complex stimulus structure: local and global levels in naturalistic scenes. AB - An information tradeoff is an increased processing or utilization of information from one stimulus source at the expense of processing or utilization of information from a different source. An experiment was conducted to determine whether information tradeoffs occurred when subjects attended selectively to one of two different structural levels of naturalistic scenes. The subjects' attentional focus was directed to either the global or local structure of a scene (i.e., the scene or an object in the scene, respectively) either before or after presentation of a scene. They then had to use the information obtained from a 100 msec exposure of the scene to choose between two forced-choice alternatives that described one of the levels. The nature of the alternatives was such that both alternatives adequately characterized one of the structural levels on the basis of physical and semantic relations within the scene. Results showed that the subjects were significantly slower and less accurate when their attentional focus and the forced-choice alternatives were at different levels of stimulus structure than when they were at the same level, providing evidence of an information tradeoff when different types of information from a scene were used. When processing information from a particular structural level, information from the other level either was less available or was not used efficiently. Furthermore, the information tradeoffs were more severe in the precue than in the postcue condition, indicating differences in the efficiency of the selectivity process. The results are interpreted with respect to the role of selective attention in processing complex stimuli such as naturalistic scenes. PMID- 1437474 TI - Properties of the recombination of one-dimensional motion signals into a pattern motion signal. AB - We have examined the human ability to determine the direction of movement of a variety of plaid patterns. The plaids were composed of two orthogonal sine-wave gratings. When the plaid components are of unequal spatial frequency or sometimes of unequal contrast, observers judge the direction of movement incorrectly. In terms of the two-stage model of Adelson and Movshon (1982), these errors may result from either a misjudgment in the perceived speeds of each of the components or a failure in the combination of one-dimensional component movements into a coherent direction of motion of the two-dimensional plaid pattern, or both. A comparison of the perceived direction of motion of plaids with the relative perceived speeds of the plaid component gratings suggest that both failures occur, but in different circumstances. The relative perceived speed of the plaid components was measured with a spatial and a temporal forced-choice technique, the former leading to larger differences. Our results support the notion that the visual system decomposes a moving plaid into oriented components and subsequently recombines the component motions. PMID- 1437477 TI - Visual and nonvisual information disambiguate surfaces specified by motion parallax. AB - Motion parallax has been shown to be an effective and unambiguous source of information about the structure of three-dimensional (3-D) surfaces, both when an observer makes lateral movements with respect to a stationary surface and when the surface translates with respect to a stationary observer (Rogers & Graham, 1979). When the same pattern of relative motions among parts of the simulated surface is presented to a stationary observer on an unmoving monitor, the perceived corrugations are unstable with respect to the direction of the peaks and troughs. The lack of ambiguity in the original demonstrations could be due to the presence of (1) non-visual information (proprioceptive and vestibular signals) produced when the observer moves or tracks a moving surface, and/or (2) additional optic flow information available in the whole array. To distinguish between these two possibilities, we measured perceived ambiguity in simulated 3-D surfaces in situations where either nonvisual information or one of four kinds of visual information was present. Both visual and nonvisual information were effective in disambiguating the direction of depth within the simulated surface. Real perspective shape transformations affecting the elements of the display were most effective in disambiguating the display. PMID- 1437476 TI - The effect of amplitude comodulation on auditory object formation in sentence perception. AB - To comprehend speech in most environments, listeners must combine some but not all sounds from across a wide range of frequencies. Three experiments were conducted to examine the role of amplitude comodulation in performing an essential part of this function: the grouping together of the simultaneous components of a speech signal. Each of the experiments used time-varying sinusoidal (TVS) sentences (Remez, Rubin, Pisoni, & Carrell, 1981) as base stimuli because their component tones are acoustically unrelated. The independence of the three tones reduced the number of confounding grouping cues available compared with those found in natural or computer-synthesized speech (e.g., fundamental frequency and simultaneity of harmonic onset). In each of the experiments, the TVS base stimuli were amplitude modulated to determine whether this modulation would lead to appropriate grouping of the three tones as reflected by sentence intelligibility. Experiment 1 demonstrated that amplitude comodulation at 100 Hz did improve the intelligibility of TVS sentences. Experiment 2 showed that the component tones of a TVS sentence must be comodulated (as opposed to independently modulated) for improvements in intelligibility to be found. Experiment 3 showed that the comodulation rates that led to intelligibility improvements were consistent with the effective rates found in experiments that examined the grouping of complex nonspeech sounds by common temporal envelopes (e.g., comodulation masking release; Hall, Haggard, & Fernandes, 1984). The results of these experiments support the claim that certain basic temporal-envelope processing capabilities of the human auditory system contribute to the perception of fluent speech. PMID- 1437478 TI - Salience of stimulus and response features in choice-reaction tasks. AB - A pattern of differential reaction time (RT) benefits obtained in spatial precuing tasks has been attributed to translation processes that operate on mental codes formed to represent the stimulus and response sets. According to the salient-features coding principle, the codes are based on the salient stimulus and response features, with RTs being fastest when the two sets of features correspond. Three experiments are reported in which the stimulus and response sets were manipulated using Gestalt grouping principles. In the first two experiments, stimuli and responses were grouped according to spatial proximity, whereas in the last experiment, they were grouped according to similarity. With both types of manipulations, the grouping of the stimulus set systematically affected the pattern of precuing benefits. Thus, in these experiments, the organization of the stimulus set was the primary determinant of the features selected for coding the stimulus and response sets in the translation process. PMID- 1437479 TI - Discrimination tests of visually influenced syllables. AB - In the McGurk effect, perception of audiovisually discrepant syllables can depend on auditory, visual, or a combination of audiovisual information. Under some conditions, visual information can override auditory information to the extent that identification judgments of a visually influenced syllable can be as consistent as for an analogous audiovisually compatible syllable. This might indicate that visually influenced and analogous audiovisually compatible syllables are phonetically equivalent. Experiments were designed to test this issue using a compelling visually influenced syllable in an AXB matching paradigm. Subjects were asked to match an audio syllable/va/either to an audiovisually consistent syllable (audio/va/-video/fa/) or an audiovisually discrepant syllable (audio/ba/-video/fa/). It was hypothesized that if the two audiovisual syllables were phonetically equivalent, then subjects should choose them equally often in the matching task. Results show, however, that subjects are more likely to match the audio/va/ to the audiovisually consistent/va/, suggesting differences in phonetic convincingness. Additional experiments further suggest that this preference is not based on a phonetically extraneous dimension or on noticeable relative audiovisual discrepancies. PMID- 1437480 TI - Effects of context on sweet and bitter tastes: unrelated to sensitivity to PROP (6-n-propylthiouracil). AB - In a double-shifting context paradigm, subjects gave magnitude estimates of the perceived intensity of qualitatively dissimilar taste substances (saccharin and quinine, sucrose and quinine) or qualitatively similar ones (saccharin and sucrose), with each pair of substances taking on different contextual sets of concentrations in different sessions. The dissimilar pairs produced substantial differential effects of context (e.g., a particular concentration of saccharin or sucrose was judged more intense than a particular quinine in one contextual setting, less intense in another), but the similar pair did not. This result accords with the hypothesis that differential context effects depend on qualitative similarity. Contrary to expectations, however, the magnitude of the context effect did not differ in tasters and nontasters of the bitter substance 6 n-propylthiouracil (PROP), groups previously shown to differ in sensitivity to bitterness in saccharin. Similarity judgments suggest that saccharin and sucrose were qualitatively alike for all subjects, regardless of sensitivity to PROP. PMID- 1437481 TI - Surface perception in pictures. AB - Subjects adjusted a local gauge figure such as to perceptually "fit" the apparent surfaces of objects depicted in photographs. We obtained a few hundred data points per session, covering the picture according to a uniform lattice. Settings were repeated 3 times for each of 3 subjects. Almost all of the variability resided in the slant; the relative spread in the slant was about 25% (Weber fraction). The tilt was reproduced with a typical spread of about 10 degrees. The rank correlation of the slant settings of different observers was high, thus the slant settings of different subjects were monotonically related. The variability could be predicted from the scatter in repeated settings by the individual observers. Although repeated settings by a single observer agreed within 5%, observers did not agree on the value of the slant, even on the average. Scaling factors of a doubling in the depth dimension were encountered between different subjects. The data conformed quite well to some hypothetical fiducial global surface, the orientation of which was "probed" by the subject's local settings. The variability was completely accounted for by single-observer scatter. These conclusions are based upon an analysis of the internal structure of the local settings. We did not address the problem of veridicality, that is, conformity to some "real object." PMID- 1437482 TI - The differentiation of rhythmic structure. AB - Listeners judged whether two five-tone nonmetric rhythms were the same or different. Each rhythm was presented one, two, or four times to study the process of perceptual differentiation. The results indicated that the listeners perceived these rhythms in terms of the grouping of the tones, and not in terms of the timing between the groups. Two rhythms that had the same perceptual grouping were judged as being identical, even if the timing between the groups was different. The perception of the groupings of tones developed gradually. If each rhythm was presented only once, then the listeners had only a global percept, focused on groups (runs) of three elements, and often judged two different rhythms as being identical. If the rhythms were presented two or four times, then the grouping of the tones became more differentiated and the listeners were less likely to judge different patterns as being identical. Thus, perception of auditory rhythmic structure appears to follow the same developmental process as the perception of visual spatial structure. PMID- 1437483 TI - Temporal factors in the discrimination of coherent motion. AB - When observers view the relative movements of a pair of bars defined by the difference of spatial Gaussian functions (DOGs), they can accurately discriminate coherent movements over a range of temporal frequencies and temporal asynchronies. Of particular interest is the fact that performance accuracy is maintained even when the two bars differ in spatial-frequency content and contrast. On each trial, observers viewed two brief presentation intervals in which a pair of vertically oriented DOGs moved randomly back and forth within a restricted range. During one observation interval, both elements moved in the same direction and by the same magnitude (correlated), and in the other interval, the movements were independent (uncorrelated). Temporal asynchronies were introduced by delaying the displacement of the right bar relative to that of the left bar in each interval. Observers were able to discriminate correlated versus uncorrelated movements up to a 45-60-msec temporal delay between the two elements' relative displacements. If motion processing is accomplished by mechanisms operating over multiple spatial and temporal scales, the visual system's tolerance of temporal delays among correlated signals may facilitate their space-time integration, thereby capitalizing on the perceptual utility of coherent-motion information for image segmentation and interpolating surface structure from the movements of spatially separated features. PMID- 1437484 TI - Infants' responsiveness to the auditory and visual attributes of a sounding/moving stimulus. AB - Responses to unimodal and multimodal attributes of a compound auditory/visual stimulus were investigated in 4-, 6-, 8-, and 10-month-old infants. First, infants were habituated to a compound stimulus consisting of a visual stimulus that moved up and down on a video monitor and a sound that occurred each time the visual stimulus reversed direction at the bottom. Once each infant met a habituation criterion, a series of test trials was administered to assess responsiveness to the components of the compound stimulus. Response was defined as the total duration of visual fixation in each trial. In the two unimodal test trials, the rate at which the component was presented was changed while the rate of the other component remained the same, whereas in the bimodal test trial the rate of both components was changed simultaneously. Results indicated that infants at each age successfully discriminated the bimodal and the two unimodal changes and that regression to the mean did not account for the results. Results also showed that disruption of the temporal relationship that accompanied the change in rate in the two unimodal test trials was also discriminable, but rate changes appeared to play a greater role in responsiveness than did synchrony changes. Considered together with results from similar prior studies, the current results are consistent with the modality appropriateness hypothesis in showing that discrimination of temporal changes in the auditory and visual modalities is dependent on the specialization of the sensory modalities. PMID- 1437485 TI - Differential thresholds for limb movement measured using adaptive techniques. AB - Differential thresholds for limb movement were measured in 10 subjects, using the transformed up-down procedure. Subjects were required to indicate which of two random displacement perturbations delivered to their forearms had the larger standard deviation (SD). The SD of the reference signal was fixed for each experimental condition at one of seven values ranging from 0.05 to 3.2 mm. THe SD of the other signal varied depending on the subject's response. Using this procedure, the differential threshold for limb movement was calculated to be 8%, which is very similar to the thresholds estimated previously for changes in limb position (9%) and force (7%). The sensitivity of the human proprioceptive system to changes in limb displacement was much greater than anticipated, with subjects being able to resolve a 5-microns difference between two perturbations delivered to their arms. PMID- 1437486 TI - The linkage between stimulus frequency and covert peak areas as it relates to monaural localization. AB - Head-related transfer functions for differently centered narrow noise bands were obtained on 6 subjects. Derived from these measurements were covert peak areas (CPAs), defined as the spatial constellation of loudspeakers that generates maximal sound pressure at the entrance of the ear canal for specific bands of frequency. On the basis of previous data, we proposed that different frequency bands served as important spectral cues for monaural localization of sounds from different loci and that location judgments were directed toward the CPAs associated with the different bands. In the first study, the stimuli were bandpass filtered so that they contained only those frequencies whose associated CPAs occupied either the monaural listener's "upper" or "lower" spatial regions. Loudspeakers, separated by 15 degrees, were stationed in the left hemifield, ranging from 0 degree to 180 degrees azimuth and -45 degrees to 60 degrees elevation. Subjects reported the loudspeaker from which the sound appeared to originate. Judgments of the sound's elevation were in general accord with the CPAs associated with the different frequency segments. In the second study, monaural localization tests were administered in which different 2.0-kHz-wide frequency bands linked with specific CPAs were notch filtered from a 3.5-kHz highpass noise band. For the control condition, the highpass noise was unfiltered. The data demonstrated that filtering a frequency segment linked with specific CPAs resulted in significantly fewer location responses directed toward that particular spatial region. These results demonstrate in greater detail the relation between the directional filtering properties of the pinna and monaural localization of sound. PMID- 1437487 TI - Intrusion patterns in rapid serial visual presentation tasks with two response dimensions. AB - A rapid serial visual presentation (RSVP) paradigm using both one and two response dimensions was used to test parallel processing models of stimulus dimensions. Fifty subjects were asked to report the identity and/or color of a target uppercase word inserted in a series of lowercase words. The results produced a predominance of posttarget intrusions for color responses and a predominance of pretarget intrusions for identity responses. The requirement of a response to a second dimension impaired hit rates but did not change the pattern of intrusions. An examination of the distributions of intrusions in each response dimension as a function of the response given to the other dimension showed an unexpectedly high percentage of simultaneous hits, a moderate covariation between both responses, and the same patterns of intrusions when compared with the general distributions. While these results seem to be compatible with parallel models of processing for stimulus dimensions, two modifications to this model are suggested. First, the processing of response dimension(s) needs some attentional resources. Second, provision for a mixed model is indicated, which would include trials where no illusory conjunctions are formed. PMID- 1437488 TI - Episodic effects on the visual comparison of letters in words. AB - In two experiments, subjects compared the identity of either the first letters of displays or all the letters in displays. Words yielded faster decisions than did pseudowords (pronounceable items derived by changing a vowel in a word) only when entire displays were compared. In a training phase run before the comparison task, subjects had written down either the first letters or entire displays. Relative to items that had not appeared in the training phase, prior experience at writing entire displays facilitated same decisions about entire displays and interfered with different decisions about entire displays. Prior experiences did not moderate the processing of first-letter identities. It was concluded that episodic effects arise from the interaction of higher order information underlying lexical encoding. Prelexical processing of letters is not sensitive to episodic effects. PMID- 1437489 TI - Local brightness mechanisms sketch out surfaces but do not fill them in: psychophysical evidence in the Kanizsa square. AB - In two experiments, brightness enhancement of the illusory surface in the Kanizsa square was investigated by means of a brightness matching procedure. The results show that specific properties of the inducing elements such as size, spacing, and luminance have effects on the matching threshold that are similar to those previously obtained in experiments on simultaneous contrast. The data from a third experiment demonstrate that increment thresholds measured within the Kanizsa square are elevated when the target is flashed on a position close to the inducing elements. The thresholds decrease considerably in the center of both test and control figures (representing or not representing an illusory square). These observations suggest that low-level mechanisms are likely to explain local brightness differences within the configurations but not global figure brightness. In other words, local contrast seems to generate brightness information that "sketches out" surfaces at their surrounds but does not "fill" them "in." PMID- 1437490 TI - Perceptual processing of adjacent and nonadjacent tactile nontargets. AB - Previous research has shown that subjects appear unable to restrict processing to a single finger and ignore a stimulus presented to an adjacent finger. Furthermore, the evidence suggests that, at least for moving stimuli, an adjacent nontarget is fully processed to the level of incipient response activation. The present study replicated and expanded upon these original findings. The results of Experiment 1 showed that an equally large response-competition effect occurred when the nontarget was presented to adjacent and nonadjacent fingers (on the same hand). The results of Experiment 2 showed that the effects observed in Experiment 1 (and in previous studies) were also obtained with stationary stimuli. Although small, there was some indication in the results of Experiment 2 that interference may dissipate more rapidly with distance with stationary stimuli. An additional finding was that interference effects were observed in both experiments with temporal separations between the target and nontarget of up to 100 msec. In Experiment 3, target and nontarget stimuli were presented to opposite hands. Although reduced, interference was still evident with target and nontarget stimuli presented to opposite hands. Varying the physical distance between hands did not produce any change in the amount of interference. The results suggest that the focus of attention on the skin extends nearly undiminished across the fingers of one hand and is not dependent upon the physical distance between sites of stimulation. PMID- 1437491 TI - Improvement in line orientation discrimination is retinally local but dependent on cognitive set. AB - The ability of human observers to discriminate the orientation of a pair of straight lines differing by 3 degrees improved with practice. The improvement did not transfer across hemifield or across quadrants within the same hemifield. The practice effect occurred whether or not observers were given feedback. However, orientation discrimination did not improve when observers attended to brightness rather than orientation of the lines. This suggests that cognitive set affects tuning in retinally local orientation channels (perhaps by guiding some form of unsupervised learning mechanism) and that retinotopic feature extraction may not be wholly preattentive. PMID- 1437492 TI - Testing models of the redundant-signals effect: a warning concerning the combination-rule regression analysis. AB - The redundant-signals effect is the observed RT advantage for trials presenting two or more targets, as compared with trials with only one target. Two general classes of parallel-processing model have been proposed to explain this effect: race models (e.g., Raab, 1962) and coactivation models (e.g., Miller, 1982). Various distributional analyses have been used in work aimed at discriminating between these two model classes. The present study reexamined one of these tests- the combination-rule regression analysis based on variable-criterion theory (Grice, Canham, & Boroughs, 1984)--by applying it to the data from two sets of simulated experiments. One set of simulations assumed coactivation; the other set assumed an independent race on redundant-target trials. Nearly identical combination-rule values were observed in the two sets of simulations. This finding shows that the combination rule of variable-criterion theory does not discriminate between models capable of explaining the redundant-signals effect. The implications of this finding are briefly discussed. PMID- 1437493 TI - Putative therapeutic applications of calmodulin antagonists. AB - Calmodulin is the most important intracellular receptor protein for the second messenger calcium. The calcium-calmodulin complex regulates a number of physiological processes. An increasing number of pharmaceutical products is reported to interfere with the calcium-calmodulin complex. Despite the fact that the precise mechanisms of action of these so-called calmodulin antagonists await further clarification, reports accumulate in the literature indicating a broadening spectrum of putative therapeutic applications of calmodulin antagonists. Some of these applications, such as in cell proliferation, hypertension, congestive heart failure, arrhythmia and gastro-intestinal disorders, are discussed in the present review. PMID- 1437494 TI - Current status of interferon alpha in the treatment of chronic hepatitis B. AB - Interferon alpha is the only available therapy for patients with chronic hepatitis B. With interferon alpha 3-15 MU thrice weekly or 5 MU daily during 3-6 months one-third of the patients achieve seroconversion of HBeAg and HBV-DNA together with normalization of aminotransferases and slight improvement of histology. Loss of HBsAg is reported in a minority of responders during treatment, but increases during follow-up. Patients with baseline alanine aminotransferase of at least twice the upper limit of normal and low HBV-DNA concentration achieve the best response rates. HIV-positive patients with low CD4 counts and Asians are poor responders. As side-effects influenza-like symptoms are experienced by almost all patients. Mild leukopenia, thrombocytopenia and decreased hairgrowth are frequently reported. Severe depression, depersonalization and psychosis are reported in a small number of patients but tend to be poorly recognized in some studies. The decision whether dose reduction is indicated seems strongly related to the opinion of the investigator. Although long-term effects on the occurrence of cirrhosis and the development of hepatocellular carcinoma are not available yet, the achieved results are promising. PMID- 1437495 TI - Knowledge of medication in hospitalized chronic respiratory patients. AB - Object of the study was to assess educative needs in the field of drug therapy among 99 chronic patients with advanced chronic lung disease admitted to the Respiratory Service of the Hospital Sta. Creu i Sant Pau (Barcelona, Spain). The knowledge of the patients about their previous drug treatment, sources of information as well as patients' conception of side-effects, was gathered from medical records and by means of a questionnaire. The majority of patients studied were male (63%), aged over 60 years (average 63 +/- 12), illiterate or with basic education (88%), had a chronic obstructive, pulmonary disease (76%) and with an important degree of chronicity. They had been treated for their condition during a mean of 8.4 years and took an average of 4.6 drugs. 31% Of patients did not answer any question about their medication properly and only 17% gave a correct answer to all the questions. The lower the age and the higher the educational level, the higher the proportion of correct answers to knowledge questions. 35% Of the patients stated not to have been informed about their medication and 55% stated that they had read the patient package inserts. PMID- 1437496 TI - Comparative study on protective gloves for handling cytotoxic medicines: a model study with carmustine. AB - The quality of protective gloves was studied. Protective gloves are part of the personal safety equipment for staff handling cytotoxic drugs. A study using raster electron microscopic photography, measurement of thickness by micrometer screw and permeability of carmustine by high pressure liquid chromatographic assay was carried out. The results show differences between different types of gloves. PMID- 1437497 TI - Disposition of quinine in rats with induced renal failure. AB - Aetiologically different models of experimental acute renal failure were induced in rats by the administration of glycerol, mercuric chloride and gentamicin, respectively, to different groups. Quinine levels in plasma and urine of the rats with induced renal failure were determined and pharmacokinetic parameters (elimination t1/2, CLp, V, CLR AUC0-infinity) of the drug were derived and compared with values obtained from control rats following intraperitoneal administration of a 10 mg/kg body-weight dose of quinine. Results showed that each of the three compounds caused an up to 25-fold increase in the plasma levels of the drug and a marked decrease in the levels of the metabolite 3 hydroxyquinine. All the pharmacokinetic parameters determined for the rats with renal impairment were markedly different when compared to control. The high plasma quinine levels observed in the rats with renal failure could be largely due to the marked decrease in V and reduced metabolism. Also, in the rats with renal impairment, no correlation was observed between the increased plasma urea levels and plasma quinine levels or disposition of the drug. The results of the study suggest that quinine should be used with caution in patients with renal impairment. The plasma urea levels, as a measure of renal function, might not provide a suitable index for determining quinine dosage. PMID- 1437498 TI - Clearance of indomethacin occurs predominantly by renal glucuronidation. AB - In this report we describe the conditions of collection, storage and handling of urine samples, collected after oral dosing with indomethacin in man, in order to maintain the integrity of the labile glucuronide formed. We found that the body clearance occurs predominantly by renal metabolism, due to glucuronidation in the human kidney. These glucuronides may be converted to isomeric glucuronides and/or the parent compound indomethacin during the residence time in the bladder. PMID- 1437499 TI - Stability of sufentanil citrate in a portable pump reservoir, a glass container and a polyethylene container. AB - The stability of sufentanil citrate (100 ml, 5 micrograms/ml) in an admixture with sodium chloride 0.9% injection was investigated when filled in a portable pump reservoir with PVC wall, a glass container and a polyethylene container, at 32 degrees C, 4 degrees C and -20 degrees C for up to 21 days. No change in colour was visually observed in any of the samples during the 21-day storage period. A slight precipitation was noticed in three out of nine portable pump reservoirs, one at each storage temperature. There was a slight rise in pH at each storage temperature in all samples. There was approximately 13% loss of sufentanil citrate in the portable pump reservoirs stored at 32 degrees C during 2 days and 60% loss after 21 days, due to absorption of sufentanil citrate in the reservoir wall. No loss of sufentanil citrate could be detected in the portable pump reservoirs when stored at -20 degrees C and 4 degrees C. However, a serious inhomogeneity of the sufentanil citrate solution occurred after thawing at room temperature in the portable pump reservoirs which had been kept at -20 degrees C. The homogeneity could be restored by shaking for approximately 10 min. There was no change in the sufentanil citrate concentrations in the glass containers and polyethylene containers stored at the three temperatures. The portable pump reservoirs stored at 32 degrees C also showed a significant loss of vehicle due to evaporation (1.0 +/- 0.1 ml a week). This could not be detected in any of the other samples. PMID- 1437500 TI - Omeprazole and its use in a university hospital: a comment. PMID- 1437501 TI - Drugs in the pipeline. Proceedings of the scientific meeting of the Dutch Association of Hospital Pharmacists. Valkenburg, 13-14 September 1991. PMID- 1437502 TI - Dealing with sadness, madness and hostility. New psychotropic drug remedies for the future. AB - The objective of this article is to present an overview of new forms of psychotropic drug therapy that may be expected to play a role in psychiatric practice in the 1990s. In predicting these future developments, three lines of approach have been followed. Firstly, progress in elucidating basic neuronal mechanisms is described. The radioligand receptor binding technique has proved to be an especially powerful tool in the search for novel psychoactive compounds. Secondly, those mental health problems most likely to undergo intensive study are discussed. It is likely that special attention will be devoted to organic mental disorders related to aging (dementia) or chronic exposure to toxic substances. In addition, research will be aimed at explaining and reducing the occurrence of auto-aggressive and hetero-aggressive behaviour. Thirdly, the types of newly designed agents and treatment strategies currently under investigation are outlined. In particular, the development of pharmacological agents that interfere with serotonergic molecular mechanisms has opened the way to improving existing psychotropic drugs, to inventing drugs that achieve known clinical effects via different mechanisms of action, and even to discovering entirely new categories of psychotropic drugs. PMID- 1437503 TI - Future developments in the pharmacotherapy of lung disease. AB - Future advances in the pharmacotherapy of lung disease will occur mainly in the treatment of asthma, and will include the development of new long-acting beta 2 agonists, long-acting parasympatholytics, phosphodiesterase inhibitors, corticosteroids with fewer systemic side-effects, and other antiinflammatory drugs. Free radicals play an important role in most lung diseases, including asthma, emphysema, fibrosis, and adult respiratory distress syndrome. The search for free radical scavengers is now in progress. Replacement therapy with alpha 1 antitrypsin and surfactant is now possible. Progress in this area stems principally from a better understanding of the pathogenesis of lung disease. PMID- 1437504 TI - Cardiovascular drugs. AB - Since the category of cardiovascular drugs comprises a considerable number of pharmacotherapeutic groups, an overview of future developments must necessarily be limited to those areas in which innovations are most likely to occur. Further extension of our knowledge of thrombolytic therapy may eventually lead to new choices of primary drugs. In the area of antiarrhythmic therapy, the clinical use of a number of drugs has been hampered by the pro-arrhythmogenic actions of these agents. The development of new class III anti-arrhythmics will continue, probably giving rise to new therapeutic options. In the vascular area a new group of drugs, the renin inhibitors, is likely to emerge for the treatment of hypertension. Moreover, exciting discoveries in vascular pharmacology should eventually translate into new pharmacotherapeutic approaches. Finally, the large scale availability of blood fractions (coagulation factors) prepared by recombinant technology may help solve current shortages of products derived from donated blood. PMID- 1437505 TI - Future directions in antimicrobial chemotherapy. AB - New developments in the treatment of bacterial infections are discussed. The most important developments include oral broad-spectrum cephalosporin derivatives and extended-spectrum injectable cephalosporins with improved activity against Gram positive bacteria. Meropenem is a new carbapenem agent with markedly improved activity against Gram-negative bacteria. Many fluoroquinolones are in various phases of development. The most interesting new compound is sparfloxacin. Azithromycin is a new macrolide which, because of its very long half-life, attains very high levels in most tissues. Potential uses of the newer agents are discussed. PMID- 1437506 TI - Immunomodulators. Future prospects. AB - The future role of the immunomodulators in medical practice is yet to be defined. The key question is whether these new substances will bring remarkable progress in transplantation or in the treatment of such conditions as cancer, AIDS, and autoimmune diseases, or whether they will be of only minor adjunctive importance. As background to the discussion of immunomodulating agents, the immune system is explained, with emphasis on the roles of T and B lymphocytes, macrophages, phagocytes, human leukocyte antigen and the complement system. Special attention is given to the cytokines, particularly the lymphokines. The immunomodulators can be divided into three main groups: immunosuppressive agents, such as FK 506 and rapamycin; immunostimulating agents, of which BCG vaccine is most important; and the remaining immunomodulators, which include the biological response modifiers. The last group, which encompasses the colony-stimulating factors (GM-CSF, G-CSF, and M-CSF), the interleukins, the interferons, and the tumour necrosis factors, is described in detail. Innovative research and medical applications of these cytokines, including indications, contraindications, and adverse reactions, are discussed. The role of monoclonal antibodies against endotoxins is also described. PMID- 1437507 TI - Delivery of hormones: some new concepts. AB - Some new concepts in the delivery of hormones are described. Transmucosal or transdermal penetration of hormones can be facilitated, often by the use of absorption enhancers. Studies of nasal insulin delivery are described. Recently developed iontophoretic delivery devices can be useful for pulsatile transdermal administration of peptide hormones. A self-regulating delivery system releasing insulin in response to glucose levels is described. A vaginal ring releasing ethinylestradiol and 3-ketodesogestrel is a new concept in long-acting contraception. A nasal estradiol formulation, containing the absorption enhancer dimethyl-beta-cyclodextrin, is an interesting alternative to oral and transdermal delivery of female sex hormones. PMID- 1437508 TI - New cytotoxic drugs and targets in oncology. AB - New agents in the preclinical and early clinical pipeline (phases I and II) are described and some of the problems associated with their development are reviewed. The article focuses on tubulin poisons such as taxol, topoisomerase inhibitors, such as topotecan, and drugs such as bryostatin 1 and miltefosin, which interfere with specific signal transduction pathways involved in malignant cell growth. PMID- 1437509 TI - Future prospects in antiviral therapy. AB - Two important stumbling blocks to the development of effective and nontoxic antiviral drugs are the intracellular localization of the virus and the fact that a virus uses host cell functions to multiply. Therefore, new antiviral drugs must act on a virus-specific function. Most currently available useful antiviral drugs are the result of compound screening of large numbers of possible agents. Advances in our understanding of the molecular biology and biochemistry of the viral multiplication cycle and new laboratory techniques for determining the molecular sites of action have now made it possible to develop and screen new antiviral drugs in a more purposeful manner. Another possible option in antiviral therapy is combination therapy using drugs that enhance the therapeutic effect or diminish side-effects. The most promising new antiviral drugs are discussed according to the different steps they affect in the viral multiplication process. Combination therapy is also reviewed. PMID- 1437510 TI - New developments in the pharmacotherapy of inflammatory bowel disease. AB - In this article the clinical features and aetiology of inflammatory bowel diseases are described and current pharmacotherapeutic possibilities are explored. Also reviewed are recent developments and future prospects for the pharmacotherapy of inflammatory bowel diseases, including aminosalicylates, corticosteroids, immunosuppressants, lipoxygenase inhibitors, fish oil, sucralfate, bismuth compounds, free radical scavengers, (hydroxy)chloroquine, sodium cromoglycate and methotrexate. PMID- 1437511 TI - Dideoxynucleoside therapy for HIV infection. PMID- 1437512 TI - Catecholamines in critical care. The commonly used catecholamines: receptor and clinical profile, indications and dosages. AB - The pharmacology, pattern of receptor activation and resulting clinical impact of the currently most widely used intravenous catecholamines are reviewed. A brief physiological description of the alpha, beta and dopaminergic receptors is used in order to explain the clinical effects of norepinephrine, epinephrine, isoproterenol, dopamine, dobutamine and dopexamine. Each drug is discussed separately according to receptor profile, indications, dosages and current application in critical care. Tables are provided for comparison of relative strengths of these drugs regarding receptor activation, haemodynamic effects, organ perfusion and recommended dosages. The use of combinations of catecholamines to meet a variety of circulatory demands is commented upon. PMID- 1437513 TI - Didanosine, a new antiretroviral drug. A review. AB - In this article the literature about didanosine, an antiretroviral drug, is reviewed. The mechanism of action, biochemical pharmacology, pharmacokinetics, and clinical results of phase-I trials are discussed. Serious adverse effects such as pancreatitis and peripheral neuropathy have occurred in these trials. An antiretroviral effect was observed in terms of an increase in CD4+ lymphocytes and a decrease in p24 antigen levels in HIV-infected individuals. Didanosine seems to be a promising drug against HIV infection, but knowledge about its clinical efficacy is scanty. PMID- 1437514 TI - Drug transport across the blood--brain barrier. I. Anatomical and physiological aspects. AB - This review describes various aspects of the transport of drugs across the blood brain barrier and comprises three parts. In this first part, the anatomical and physiological aspects of blood-brain transport are discussed. It appears that the blood-brain barrier has an anatomical basis at the endothelium of the capillary wall. This endothelium is characterized by the presence of very tight junctions. As a result, the transport by passive diffusion of drugs with a low lipophilicity, is restricted. For certain classes of closely related relatively hydrophilic compounds, however, the presence of specialized carrier systems has been demonstrated which may facilitate transport. Also evidence is presently available, that the permeability of the blood-brain barrier may be under active regulatory control. It is expected that improved knowledge of the anatomical and physiological aspects of the blood-brain barrier and its regulation will provide a scientific basis for the development of strategies to improve the transport of drugs into the central nervous system. PMID- 1437515 TI - The comprehensiveness of Medline and Embase computer searches. Searches for controlled trials of homoeopathy, ascorbic acid for common cold and ginkgo biloba for cerebral insufficiency and intermittent claudication. AB - OBJECTIVE: To assess the comprehensiveness of Medline and Embase computer searches for controlled trials. DESIGN: Comparison of articles found after an exhaustive search of the literature with the yield of a Medline or Embase search. This was performed for controlled clinical trials on the efficacy of three interventions: homoeopathy, ascorbic acid for common cold, and ginkgo biloba for intermittent claudication and cerebral insufficiency. The number of controlled trials found by exhaustive search of the literature was 107, 61 and 45, respectively. RESULTS: For homoeopathy, ascorbic acid and ginkgo the proportion of all trials found by Medline was 17%, 36% and 31% respectively and for Embase 13%, 25% and 58% respectively. After checking of the references in the Medline articles 44%, 79% and 76% of all trials were identified. After checking of the references in the Embase articles 42%, 72% and 93% of all trials were identified. About 20% of the articles was not correctly indexed. Of the best trials 68%, 91% and 83% could be found with Medline and 55%, 82% and 92% of the best trials were identified through Embase. CONCLUSIONS: For the topics mentioned, Medline and Embase searches are sufficient to get an impression of the evidence from controlled trials, but only if references in the articles are followed for further evidence. If one wants to get a more complete picture, additional search strategies make sense. Of course, this picture may be different for other topics. PMID- 1437516 TI - Assessment of trace element compatibility in total parenteral nutrition infusions. AB - The application of X-ray energy dispersive spectroscopy to detect elements collected from TPN mixtures on membrane filters has been investigated. Many simple total parenteral nutrition mixtures prepared aseptically in large bags can be stored for extended periods. Trace elements are normally excluded from such bags, because not enough is known about their long-term stability and compatibility in total parenteral nutrition mixtures. Assessing the compatibility of many trace elements by conventional methods that rely on detecting concentration changes is extremely difficult. Analysis of precipitates from total parenteral nutrition mixtures confirmed that the proposed method was capable of identifying a number of elements from the mixture in complex precipitates, including calcium, phosphorus, iron, copper and selenium. PMID- 1437517 TI - Capacity-limited renal glucuronidation of probenecid by humans. A pilot Vmax finding study. AB - Probenecid shows dose-dependent pharmacokinetics. When in one volunteer the dose is increased from 250 to 1,500 mg orally, the t1/2 increased from 3 to 6 h. The Cmax was 14 micrograms/ml with a dosage of 250 mg, 31 micrograms/ml with 500 mg, 70 micrograms/ml with 1,000 mg and 120 micrograms/ml with 1,500 mg. The tmax remained 1 h for all four dosages. The AUC/dose ratio increased with the dose, indicating nonlinear elimination. The total body clearance declined from 64.5 ml/min for 250 mg to 26.0 ml/min for 1,500 mg. The renal clearance of probenecid remained constant, 0.6-0.8 ml/min. Protein binding of probenecid is high (91%) and independent of the dose. The phase I metabolites show lower protein binding values (34-59%). The protein binding of probenecid glucuronide in vitro (spiked plasma) is 75%. Probenecid is metabolized by cytochrome P-450 to three phase I metabolites. Each of the metabolites accounts for less than 10% of the dose administered; the percentage recovered in the urine is independent of the dose. The main metabolite probenecid glucuronide is only present in urine and not in plasma. The renal excretion rate--time profile of probenecid glucuronide shows a plateau value of approximately 700 micrograms/min (46 mg/h) with acidic urine pH. The duration of this plateau value depends on the dose: 2 h at 500 mg, 10 h at 1,000 mg and 20 h at 1,500 mg. It is demonstrated that probenecid glucuronide must be formed in the kidney during its passage of the tubule. The plateau value in the renal excretion rate of probenecid value reflects its Vmax of formation. PMID- 1437518 TI - Intramembrane charge movement in developing skeletal muscle cells from fetal mice. AB - The development of intramembrane charge movement was studied in freshly isolated skeletal muscle cells from 13- to 19-day-old mouse fetuses. Charge movement was present in myotubes from 13-day-old fetuses. The relationship between charge movement and membrane potential could be described by a two-state Boltzmann equation. The amount of maximum charge movement (Qmax) increased substantially with the age of the fetuses from 2.84 +/- 0.39 nC/microF (n = 10) at day 13 to 10.01 +/- 0.97 nC/microF (n = 15) at day 19. Nifedipine (1 microM) consistently reduced Qmax by 33 +/- 2% (n = 37) of the control value at each age studied. Increasing the concentration of nifedipine to 20 microM had no further effect, suggesting that the charge movement in developing myotubes consists of at least two components: a nifedipine-sensitive charge movement (Qns) and a nifedipine resistant one (Qnr). Both Qns and Qnr increased exponentially with a distinct enhancement of rate at day 16. PMID- 1437519 TI - Estimating transit time for capillary blood in selected muscles of exercising animals. AB - The mean minimal capillary transit time was estimated in muscles of various animals using a combination of physiological and morphometric methods. Radioactive microspheres were injected intravascularly in various animals running on a treadmill at maximum oxygen consumption rate (VO2,max) to label blood flow to individual muscles. The muscles were then removed and preserved by standard methods for electron microscopy. The volume density of mitochondria was measured to assess muscle oxidative capacity. Capillary densities in muscle cross sections, capillary diameters and tortuosities were incorporated into an estimate of capillary volume per unit muscle mass. Mean capillary transit time (tc) in the exercising muscles was estimated by dividing mass-specific capillary volume by mass-specific blood flow. Estimates of tc ranged from values near 1 s in horse heart and thigh muscles to 0.2 s in duck gastrocnemius. The relationship between muscle blood flow and tc was hyperbolic. The experimental data indicate a limiting value of 0.2 s for transit times at very high blood flows. There was no correlation between tc and body-mass-specific VO2,max. PMID- 1437520 TI - The reflex effect of changes in renal perfusion on hindlimb vascular resistance in anaesthetized rabbits. AB - This study was designed to characterise the response of the hindlimb vasculature to reduced renal perfusion in the anaesthetized rabbit and to elucidate whether the stimulus was dependent upon reduced renal perfusion pressure (RPP) or blood flow (RBF). Acute decreases in renal perfusion resulted in rapid and reversible increases in femoral perfusion (FPP). This vascular response was completely abolished following renal denervation indicating that the afferent components of the reflex is neurally mediated. Acute hindlimb responses to changes in renal perfusion pressure were present whether the limb was perfused with homologous blood or cross-perfused with blood from a donor rabbit, demonstrating that the efferent component of the response is also neurally mediated. There was a 28-s latency for initiation of the hindlimb vasoconstriction, which is consistent with recent evidence for renal autocoid stimulation of the afferent renal nerve receptors. Decreasing RPP indirectly, by altering flow, resulted in a hindlimb vasoconstriction below approximately 55 mm Hg (7.3 kPa) RPP or 15 ml/min RBF. However, decreasing RPP by directly reducing pressure in graded steps resulted in increases in FPP, which reflected the changes in renal flow; thus during the autoregulatory phase, where flow did not change as pressure fell, FPP also remained stable. The results of these protocols suggest that a neurally mediated hindlimb vascular reflex is stimulated by decreased renal flow rather than pressure. PMID- 1437521 TI - Membrane conductance and cell volume changes evoked by vasoactive intestinal polypeptide and carbachol in small intestinal crypts. AB - We have used the perforated-patch whole-cell recording mode of the patch-clamp technique to monitor membrane potential and measured cell volume changes by image analysis, to determine the nature of the response to secretagogues of isolated whole guinea-pig small-intestinal crypts. Vasoactive intestinal polypeptide (VIP) produced a dose-dependent depolarisation (EC50 = 30 nM) and an increase in membrane conductance that could be potentiated by carbachol. Similar depolarisations were observed with forskolin. The depolarisation induced by 100 nM VIP was smaller when pipette [Cl-] was 60 mM than when it was 145 mM, suggesting an effect through Cl- conductance activation. Carbachol alone produced a hyperpolarisation (EC50 = 2 microM). The Cl- channel blocker 5-nitro-2-(3 phenylpropylamino)-benzoic acid (NPPB) produced a small hyperpolarization. When VIP was added in the presence of NPPB, the depolarisation was observed instead, consistent with the parallel activation of a K+ conductance. Both carbachol (100 microM) and VIP (100 nM) induced a 25%-30% shrinkage of crypts, which was maximal 8 min after addition of the secretagogue. The induced shrinkage was sustained in the continued presence of agonist and was reversed upon washout. Shrinkage induced by the agonists was abolished by increasing extracellular K+ from 6 mM to 20 mM and was inhibited partially in the presence of 100 microM anthracene-9 carboxylic acid in the bath. The decrease in volume induced by 100 nM VIP was totally abolished in the presence of 100 microM NPPB. The results are consistent with the view that both VIP and carbachol induce secretion in small-intestinal crypts. PMID- 1437522 TI - Contractile activation properties of ventricular myocardium from hypothyroid, euthyroid and juvenile rats. AB - Contractile activation properties of intact and chemically skinned ventricular myocardium preparations were studied in juvenile (3-4 weeks old), adult euthyroid and adult hypothyroid rats. The rats were made hyperthyroid by treatment with iodine-131 and propylthiouracil. The ventricular muscle of euthyroid rats contains a mixture of isozymes of myosin while the myocardium of juvenile and hypothyroid rats are relatively pure in regard to V1 and V3 types of myosin respectively. No significant differences were found in either the maximum Ca2+ activated or rigor force developed by "chemically skinned" preparations in either the juvenile or hypothyroid groups compared with euthyroid adults, suggesting that there is no difference between myocardia with different isozymes of myosin in the intrinsic capacity to generate force. In the hypothyroid (V3) preparations there was a significant shift in the force/pCa relation to the left compared with the euthyroid adult (mixture of V1 and V3 isozymes). The force/pCa relation for the juvenile lay in between that for the hypothyroid and euthyroid adults. The greater apparent Ca2+ sensitivity to activation in the hypothyroid group may relate to a slower cross-bridge cycling rate or altered Ca2+ kinetics in ventricular myocardium with exclusively V3 isozyme. In intact papillary muscles differences were found in the dependence of force on extracellular [Ca2+] such that a higher extracellular [Ca2+] was required for muscles from hypothyroid animals to attain maximum twitch force than those from juveniles. The force/frequency relations also differed, with the hypothyroid group being better able to sustain force as stimulation frequency increased than the juvenile group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437523 TI - The effects of intracellular and extracellular alkalinization on contractions of the isolated rat uterus. AB - The effects of changing pH on a spontaneously active smooth muscle, the myometrium, is examined. We show, for the first time in any smooth muscle, that the frequency of contraction is greatly increased when intracellular pH is raised. Three weak bases, trimethylamine, diethylamine and ammonium, were used to raise intracellular pH (pHi), at constant external pH, in isolated uteri of pregnant and non-pregnant rats. Each base increased spontaneous uterine contractile activity, particularly by raising the frequency, in a concentration dependent manner. At the highest concentrations (40-50 mM) frequency was so increased that a maintained contraction resulted. Intracellular alkalinization during a high-K-maintained uterine contraction produced a small, but significant, fall in force. When external pH was increased, the results were greatly influenced by gestational state; in uteri from non-pregnant animals there was no effect whereas uteri from pregnant rats were found to be extremely sensitive to a raised external pH above 7.4; spontaneous contractions were reduced. In pregnant uteri, when both internal and external pH were elevated, spontaneous contractions were immediately reduced, thus the effects of external pH predominated. These findings may have significance in labour. PMID- 1437525 TI - Acetazolamide inhibition of basolateral Cl-/HCO3- exchange in rabbit renal proximal tubule S3 segment. AB - Cell pH (pH(i)) and cell membrane potential (Vb) were measured in isolated S3 segments of rabbit renal proximal tubule with double-barrelled microelectrodes to search for a possible effect of the carbonic anhydrase inhibitor, acetazolamide (ACZ), on Cl-/HCO3- exchange in the basolateral cell membrane. ACZ was found to retard and reduce the pH(i) response to bath Cl- removal reversibly with half maximal inhibition at 0.42 mmol/l and a rather flat concentration dependence (Hill coefficient approximately 0.36). To determine whether the retardation resulted from inhibition of cytoplasmic carbonic anhydrase, which might have delayed the attainment of HCO3-/CO2 equilibrium, we have measured the response of pH(i) to step changes in PCO2 in the presence and absence of ACZ. ACZ greatly retarded the pH(i) response to CO2 steps; however, the concentration dependence differed (half-maximal inhibition at 18 mumol/l) and even at maximal ACZ concentrations the response to CO2 steps was more than twice as fast as the response to Cl- replacement. Since, in addition, the ACZ inhibition of Cl-/HCO3- exchange could not be overcome by increasing PCO2 we conclude that the ACZ effect on Cl-/HCO3- exchange in rabbit proximal tubule S3 segments does not result from inhibition of cytosolic or membrane-bound carbonic anhydrase, but from a direct interaction with the exchanger molecule. PMID- 1437526 TI - Acetazolamide inhibition of basolateral base exit in rabbit renal proximal tubule S2 segment. AB - The influence of the carbonic anhydrase inhibitor acetazolamide (ACZ) was investigated on HCO3- transport mechanisms in the basolateral cell membrane of rabbit renal proximal tubule. Experiments were performed on isolated S2 segments using double-barrelled microelectrodes to measure cell membrane potential (Vb) and cell pH (pH(i)) during step changes in bath perfusate ion concentrations. Peritubular application of ACZ (1 mmol/l) reduced the initial Vb response to 10:1 reduction of bath HCO3- concentration only slightly, from +53.8 +/- 4.2 mV to +49.1 +/- 0.3 mV (n = 5), but caused an intermittent overshooting repolarization in the secondary Vb response. In conjunction with these effects it left the initial pH(i)) response virtually unchanged but induced a secondary slow acidification. These observation indicate that--under the present experimental conditions--ACZ does not block the Na(+)-HCO3- cotransporter but acts via inhibition of cytosolic carbonic anhydrase. This was confirmed by studying the effect of elevated intracellular HCO3- concentrations under reduced flux conditions and by comparing the concentration dependence of the Vb response with the inhibition kinetics of cytosolic carbonic anhydrase. In contrast, peritubular ACZ inhibited Na(+)-independent Cl-/HCO3- exchange in the basolateral cell membrane of S2 segments directly in a similar way to that described in the preceding publication for S3 segments. PMID- 1437524 TI - Intracellular Ca2+ signalling is modulated by K+ channel blockers in colonic epithelial cells (HT-29/B6). AB - We investigated the inhibitory action of K+ channel blockers on carbachol stimulated Ca2+ entry into human Cl(-)-secretory colonic epithelial cells (HT 29/B6). Digital imaging of the fluorescent calcium indicator dye fura-2 was performed to monitor effects of K+ channel blockers on cytosolic calcium in resting and carbachol-stimulated HT-29/B6 cells. Stimulation with the muscarinic agonist carbachol (100 microM) caused a clearly biphasic intracellular calcium (Cai) response: Cai was stimulated from resting levels (85 +/- 3 nM, n = 100) to a sudden transient peak (821 +/- 44 nM) followed by a sustained plateau (317 +/- 12 nM). The maintained elevation was dependent on external Ca2+ and represented a new steady state between Ca2+ entry and exit across the plasma membrane. A monophasic Ca2+ response was induced in the absence of external Ca2+ and after the initial peak Cai returned to baseline. The Cai plateau was reduced to resting levels by either the muscarinic antagonist atropine (1 microM) or the inorganic Ca2+ channel blocker lanthanum (effective concentration for 50% inhibition of Cai plateau EC50 = 68 +/- 18 nM), but it was unaffected by the organic Ca2+ channel blockers verapamil and nifedipine. Barium, lidocaine and 4-nitro- 2-(3 phenylpropylamino)benzoate (NPPB), well-known blockers of basolateral K+ channels of HT-29/B6 cells, rapidly and reversibly reduced carbachol-stimulated Ca2+ entry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437527 TI - G-protein-mediated regulation of a Ca(2+)-dependent K+ channel in cultured vascular endothelial cells. AB - The purpose of the present study was to determine the mechanism by which bradykinin activates the small conductance, inwardly rectifying, Ca(2+)-activated K+ channel (KCa) found in cultured bovine aortic endothelial cells. Channel activity was studied using the patch-clamp technique in whole-cell, cell attached, inside-out and outside-out configurations. Channel conductance at potentials positive to 0 mV was 10 +/- 2 pS and at potentials negative to 0 mV 30 +/- 3 pS (n = 7) when examined in symmetrical K+ (150 mmol/l) solutions. The channel open probability (P(o)) was only weakly voltage dependent changing approximately 0.2 units over 160 mV. In contrast, raising the intracellular Ca2+ concentration from 100 nmol/l to 10 mumol/l at -60 mV produced a graded increase in channel P(o) from 0.15 to 0.96; the concentration required for half-maximum response (apparent K0.5) was 719 nmol/l. At a constant Ca2+ concentration, application of guanosine triphosphate (GTP) to the cytoplasmic surface of the patch increased channel P(o). This effect was dependent upon the simultaneous presence of both GTP and Mg2+, and was reversed by the subsequent application of the guanosine diphosphate (GDP) analogue, guanosine-5'-O-(2-thiodiphosphate) (GDP beta S). The hydrolysis-resistant GTP analogue, guanosine-5'-O-(3 thiotriphosphate) (GTP gamma S), induced a long-lasting increase in channel P(o). In the presence of Mg(2+)-GTP, the apparent K0.5 for Ca2+ decreased from a control value of 722 nmol/l to 231 nmol/l. Addition of bradykinin to outside-out patches previously exposed to intracellular Mg(2+)-GTP further enhanced KCa activity, shifting the apparent K0.5 for Ca2+ from 228 nmol/l to 107 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437528 TI - Activation of cationic amino acid transport through system y+ correlates with expression of the T-cell early antigen gene in human lymphocytes. AB - Lysine influx (2 microM) into activated human B and T lymphocytes through transport systems y+ and y+L was measured. In activated T cells very substantial activation of system y+ was detected; system y+L was also activated in these cells but with a slower time course and to a smaller extent. No stimulation of either system was found in activated B cells. The time course of activation of system y+ precisely matched the expression of the T cell early antigen gene described by MacLeod et al, 1990. The functional significance of these observations with respect to L-arginine transport and nitric oxide synthesis in activated T lymphocytes is discussed. PMID- 1437529 TI - [Adverse reactions to low osmolar iodine contrast media (second report)]. AB - From January to December 1990, we performed a prospective survey of adverse reactions to contrast media at two different institutes of Juntendo University. We collected a total of 4555 case sheets during the period. The radiological procedures we investigated were computed tomography, intravenous urography, arteriography, venography and myelography. Low osmolar iodine contrast medium was used almost exclusively (except for five cases). The overall incidence of adverse reactions was 7.0%, and there were no severe or fatal reactions. The incidence of adverse reactions was higher in females (8.5%) than in males (6.1%). The incidence of adverse reactions increased according to the dose of contrast medium, especially when more than 101 ml was injected. Intra-arterial injection caused adverse reactions most often, followed by regular intravenous injections, followed by bolus intravenous injections. Adverse reactions occurred most often during injection. The next occurred in 5 minutes after injection, and then, 5-10 minutes after the injection of contrast medium. The incidence of adverse reactions was higher in patients with a history of allergy or previous reactions. Allergic adverse reactions were observed at a higher frequency. Pretesting was performed in 56.7% of the cases. PMID- 1437530 TI - [Pseudodynamic MR imaging of temporomandibular joint disorders]. AB - Magnetic resonance (MR) imaging of the temporomandibular joint (TMJ) has now been established as a procedure of choice in the evaluation of TMJ disorders. In this study, we evaluated the dynamics of TMJ motion on MR imaging, which resembles arthrography. Sixty-eight TMJs in 38 symptomatic patients and one healthy volunteer were examined using pseudodynamic images with gradient echo sequences using a 0.5 Tesla MR unit and 8 cm circular planar surface coil. For depiction of each compartment of the meniscus, the optimum sequence was 200/15/2 (TR/TE/excitations) with 50 degrees or 60 degrees flip angle in gradient refocused acquisition in steady-state (GRASS) sequences. Three contiguous slices on sagittal MR images were routinely obtained at 14-18 different phases of the opening cycle and displayed in closed-loop cine fashion. Internal derangement was observed in 57% of 68 joints. The most common type was anterior meniscal displacement without reduction. Sideway and rotational displacements, observed in 10% each, were noted on both sagittal multislice images and axial reference images. As a pseudodynamic MR technique, jaw movement specifically designed to check bite procedure to adjust splints is useful for detecting the exact time of meniscal redisplacement on the second click. After conservative therapy for arthrosis, pseudodynamic MR provided information on changes in the meniscus and condylar relationship. Pseudodynamic MR with multiple phases is suitable for evaluating subtle motion abnormality of the meniscus and for post-therapeutic monitoring. PMID- 1437531 TI - [Hemodynamics in the territory of balloon occluded internal iliac artery- problems of balloon occluded arterial infusion therapy for urinary bladder cancer]. AB - Balloon occluded arterial infusion therapy (BOAI) with anticancer drugs has been performed widely for urinary bladder cancer. It is expected that a dense anticancer drug would perfuse the territory of the vesical arteries under occlusion of the bilateral internal iliac arteries. In balloon occluded internal iliac arteriography, however, contrast media are gradually washed out in spite of complete occlusion of the bilateral internal iliac arteries. This washout process takes place via collateral flow to the acute occlusion and varies according to the position of occlusion and arterial variations in branching. We wondered whether anticancer drug administered by BOAI would perfuse the territory of the vesical arteries as expected. We analyzed the washout process of balloon occluded internal iliac arteriography in 41 patients with urinary bladder cancer in whom preoperative BOAI had been performed. We estimated the hemodynamics and perfusion of the anticancer drug to the urinary bladder on the basis of analysis of balloon occluded internal iliac arteriography in each case. Perfusion scintigraphy and histological examination of surgical specimens of urinary bladder cancer (21 cases) confirmed the validity of our estimates. In some cases it was presumed that the anticancer drug did not reach the territory of the vesical arteries. PMID- 1437532 TI - [CT of pulmonary dirofilariasis--differential diagnosis from lung cancer]. AB - We present here four cases of pulmonary dirofilariasis in which histological examination of the surgical specimen showed occlusion of the peripheral pulmonary artery by filariae and formation of a necrotic mass surrounded by reactive inflammation and hemorrhage. Radiological examination showed a solitary pulmonary nodule in three cases and a wedge-shaped consolidation in one case. Although pulmonary nodules in dirofilariasis closely mimic bronchogenic carcinoma on radiographs , it is possible to distinguish them from bronchogenic carcinoma on the basis of the following findings: (1) coexistence of subtle satellite lesions, (2) absence of pleural involvement, (3) fine marginal speculations, and (4) lack of concentric marginal speculations (eccentric speculation). In each case of dirofilariasis, CT showed the peripheral pulmonary artery entering the mass. This finding differentiates this disease from metastatic lung tumor, because in tumor metastasis via the pulmonary arteries, visible vessels are not usually involved. PMID- 1437533 TI - [CT assessment of gallbladder opacification 12-24 hours after angiography]. AB - After the injection of conventional contrast agents that are largely excreted in urine, gallbladder opacification is observed in patients with renal dysfunction. However, some reports have noted that gallbladder opacification on plain radiographs occurs frequently in patients without renal impairment after the intravenous administration of Ioxaglate, one of the new low-osmolality agents. We carried out CT examination 12-24 hours after angiography with various kinds of contrast media in 437 patients to examine the incidence of gallbladder opacification. The influence of hepatobiliary and renal function on the excretion of contrast medium is discussed. Gallbladder opacification was observed in more than 60% of the patients. This result indicates that gallbladder opacification is not a rare phenomenon, and is even common in delayed CT examinations of patients with normal renal function. The high frequency of gallbladder opacification was recognized not only in the renal dysfunction group but also in the normal liver function group. Gallbladder opacification in delayed CT examination shows that the hepatobiliary tract is important in the excretion of contrast medium. PMID- 1437534 TI - [Preclinical evaluation of iotrolan as a contrast medium for angiography and urography]. AB - Efficacy and tolerability of iotrolan, a nonionic isotonic dimer, as a contrast medium for angiography and urography were investigated in animals. In the arteriography of rabbit femur, the efficacy of iotrolan 280 mgI/ml was as good as iopamidol 300 mgI/ml and better than meglumine diatrizoate 306 mgI/ml. In rat urography, the efficacy of iotrolan 280 mgI/ml was better than both iopamidol 370 mgI/ml and iohexol 350 mgI/ml. Vascular pain was less with iotrolan 280 mgI/ml than with iohexol 300 mgI/ml in rats. Effect of iotrolan on the pulmo cardiovascular parameters, arterial pO2, hematocrit and plasma osmolality was less than iopamidol and diatrizoate in rabbits. Iotrolan induced no renal dysfunction and diuresis where iopamidol induced diuresis in rats. Effect of iotrolan on the blood coagulation was similar to nonionic monomers and less than diatrizoate in rabbits. Because of its isotonicity, iotrolan induced little water shift in the blood vessel and urinary tract, which would result in good efficacy and tolerability. These results suggest that iotrolan is superior to ionic and nonionic monomers for angiography and urography. PMID- 1437535 TI - [Clinical evaluation of lumbosacral nerve root and lateral stenosis using coronal MR imaging]. AB - MR imaging is being used more frequently to study the lumbar spine and is becoming the modality of choice in the assessment of patient with low back pain. Using a new technique of coronal and half coronal scan with MR imaging, it was possible to visualize L4, L5 and S1 nerve roots accurately. We described the MR findings of lateral stenosis using this technique. Several characteristic MR findings were identified, and the most important one was nerve root impingement in the intervertebral foramen. We consider that coronal and half coronal scan with MR imaging is useful in diagnosis of lateral stenosis. PMID- 1437536 TI - [The value of frequent positioning of treatment field in radiotherapy of esophageal cancer]. AB - Since 1983 a clinical trial of proton beam radiotherapy has been conducted at the Proton Medical Research Center (PMRC) of the University of Tsukuba. We have made it a rule to do field localization by X-ray pictures before each treatment. For this purpose we have developed a localize-verify system consisting of a fluoroscopic unit and a real time digital image processing device. By using this system as well as X-ray films, field placement errors or corrected distance at field localization were measured in 11 patients with esophageal cancers. Measurements of corrected distances on a total of 177 localization attempts disclosed that correction by > 5 mm was necessary in 30.6% and by > 10 mm in 10.2% of all localization attempts. Corrected distances appeared to increase with age, possibly because the skin becomes looser and ambulatory status tends to be more limited in older patients. Field placement corrections of more than 5 mm were required in 66.7% of 60 localizations in patients > 80 years old. Two patients in whom the anatomical positions of the esophagus were easily movable are presented. The following common characteristics of these patients were considered high risk factors: they were more than 80 years old; lesions were located in the lower esophagus; and they had T1 tumors. These findings suggested that frequent positioning and verification of treatment fields are necessary in the accurate treatment of esophageal cancers, especially those in high-risk patients. PMID- 1437537 TI - [Detectability of diagonal branch disease by 201TlCl exercised myocardial scintigraphy]. AB - The detectability of diagonal branch disease in 10 patients (five with angina pectoris, five with myocardial infarction) with isolated diagonal branch lesions (more than 75% luminal stenosis in coronary angiography) was reviewed. In exercised 201TlCl myocardial scintigraphy, chest pain occurred in four of 10 patients, electrocardiographic change indicating myocardial ischemia was seen in four, and diagonal branch lesion was detected in only four patients by planar images. In contrast, diagonal branch lesions were detected in 10 of 10 patients by SPECT (single photon emission computed tomography). In planar images, perfusion defects appeared high in the anterolateral, posterolateral, and anterior walls of the left ventricle. In SPECT images they appeared high in the anterior to anterolateral wall. The extent of diagonal branch lesions could be quantitatively evaluated by coronary territory maps developed from unfolded maps of exercised SPECT. The mean ratio of the extent of diagonal branch lesion to left anterior descending branch territory was 24.7%, and the extent of myocardial infarction was significantly larger than that of angina pectoris (p < 0.05). In conclusion, SPECT is useful for detecting diagonal branch lesions and can quantitatively show the extent of these lesions by coronary territory map. PMID- 1437538 TI - [Utility of helical CT for the secondary mass screening of lung cancer]. AB - From December 1991 to 1992, helical CT scan was performed in 55 patients with having abnormal shadow in the chest X-ray on the secondary screening for lung cancer. In all patients with suspected pulmonary lesions at first screening, helical CT scan was performed with 10 mm slice thickness for 300 mm. The moving speed of the patients table is 20 mm/l rot./1.5 sec for 300 mm in a single breath hold. Helical CT allowed shortening of examination time and providing both better data continuity and resolution than conventional CT. In conclusion, helical CT can be useful for secondary screening of lung cancer but it was considered that there are some problems such as method of final pathological diagnosis and treatment for small nodular lesion. PMID- 1437539 TI - [MR imaging during arterio-portography (MR-AP) in the detection of hepatic cancer]. AB - Magnetic resonance imaging during arterio-portography (MR-AP) was performed in 2 patients of hepatic cancer. Low dose of meglumine gadopentetate (4 ml of a 0.5 mmol/L solution) was injected into a superior mesenteric artery during acquisition of a Turbo-FLASH sequence. An increase in liver to lesion contrast was obtained with MR-AP and it is also useful in the late phase to distinguish a flow defect lesion due to portal obstruction from the tumor. PMID- 1437540 TI - [Transjugular intrahepatic portosystemic shunt: a case report]. AB - Transjugular intrahepatic portosystemic shunt (TIPS) was performed in one patient with refractory esophageal varices due to portal hypertension by liver cirrhosis. Rosch modified Z-stent was placed to keep the lumen. The shunt lowered average portal pressure from 45 to 24 mmHg, and then decompressed the esophageal varices. The shunt was patent still for three months after the creation. No significant complication was observed. This initial success of TIPS in Japan encouragingly support the safeness and effectiveness of this therapy. PMID- 1437541 TI - New Jersey State Nurses' Association history: what is past is prologue. PMID- 1437542 TI - Organ referrals: would nurses do more if they knew more? PMID- 1437543 TI - Impairment: to report or not to report--is there a choice? PMID- 1437544 TI - The writer's workbook: health professionals guide to getting published. PMID- 1437545 TI - State-approved schools of nursing L.P.N./L.V.N. 1992. PMID- 1437547 TI - Oligonucleotide-directed triple helix formation at adjacent oligopurine and oligopyrimidine DNA tracts by alternate strand recognition. AB - A significant limitation to the practical application of triplex DNA is its requirement for oligopurine tracts in target DNA sequences. The repertoire of triplex-forming sequences can potentially be expanded to adjacent blocks of purines and pyrimidines by allowing the third strand to pair with purines on alternate strands, while maintaining the required strand polarities by combining the two major classes of base triplets, Py.PuPy and Pu.PuPy. The formation of triplex DNA in this fashion requires no unusual bases or backbone linkages on the third strand. This approach has previously been demonstrated for target sequences of the type 5'-(Pu)n(Py)n-3' in intramolecular complexes. Using affinity cleaving and DNase I footprinting, we show here that intermolecular triplexes can also be formed at both 5'-(Pu)n(Py)n-3' and 5'-(Py)n(Pu)n-3' target sequences. However, triplex formation at a 5'-(Py)n(Pu)n-3' sequence occurs with lower yield. Triplex formation is disfavored, even at acid pH, when a number of contiguous C+.GC base triplets are required. These results suggest that triplex formation via alternate strand recognition at sequences made up of blocks of purines and pyrimidines may be generally feasible. PMID- 1437546 TI - Yeast SKO1 gene encodes a bZIP protein that binds to the CRE motif and acts as a repressor of transcription. AB - We have cloned a yeast gene, SKO1, which in high copy number suppresses lethal overexpression of cAMP-dependent protein kinase. SKO1 encodes a bZIP protein that binds to the CRE motif, TGACGTCA. We found that SKO1 also binds to a CRE-like site in SUC2, a yeast gene encoding invertase which is under positive control by cAMP. A disruption of the SKO1 gene causes a partial derepression of SUC2, indicating that SKO1 is a negative regulator of the SUC2 gene. SKO1 interacts positively with MIG1, a zinc finger protein that mediates glucose repression of SUC2. A kinetic analysis revealed a complex regulation of the SUC2 mRNA in response to glucose. First, MIG1 mediates a rapid and strong repression of SUC2, which is complete within 10 minutes. Second, a MIG1-independent process causes a further slow reduction in the mRNA. Third, in the absence of MIG1, there is also a rapid but transient glucose induction of the SUC2 mRNA. This induction is correlated with a transient loss of SKO1-dependent repression. PMID- 1437548 TI - Evolution of codon usage patterns: the extent and nature of divergence between Candida albicans and Saccharomyces cerevisiae. AB - Codon usage in a sample of 28 genes from the pathogenic yeast Candida albicans has been analysed using multivariate statistical analysis. A major trend among genes, correlated with gene expression level, was identified. We have focussed on the extent and nature of divergence between C.albicans and the closely related yeast Saccharomyces cerevisiae. It was recently suggested that significant differences exist between the subsets of preferred codons in these two species [Brown et al. (1991) Nucleic Acids Res. 19, 4293]. Overall, the genes of C.albicans are more A + T-rich, reflecting the lower genomic G + C content of that species, and presumably resulting from a different pattern of mutational bias. However, in both species highly expressed genes preferentially use the same subset of 'optimal' codons. A suggestion that the low frequency of NCG codons in both yeast species results from selection against the presence of codons that are potentially highly mutable is discounted. Codon usage in C.albicans, as in other unicellular species, can be interpreted as the result of a balance between the processes of mutational bias and translational selection. Codon usage in two related Candida species, C.maltosa and C.tropicalis, is briefly discussed. PMID- 1437549 TI - RFP is a DNA binding protein associated with the nuclear matrix. AB - We reported that the RFP gene encodes a protein with putative zinc finger domains and was involved in the activation of the ret proto-oncogene. To further characterize the RFP protein, we developed a polyclonal antibody against the product synthesized from a fragment of the RFP cDNA expressed in Escherichia coli. Western blot analysis showed that RFP was identified as a 58 kDa protein in cell lysates from four human and rodent cell lines and from mouse testis. In addition, a unique 68 kDa protein was detected in the testis. Using AH7974 (rat ascites hepatoma) and Raji (human Burkitt lymphoma) cells, we demonstrated strong association of RFP with the nuclear matrix. Furthermore, RFP solubilized from the nuclear matrix had DNA-binding activity although it appears to bind more preferentially to double-stranded DNA than to single-stranded DNA. These results thus suggest that RFP may play a role in molecular processes which occur in the nuclear matrix. PMID- 1437550 TI - Random mutagenesis of the human immunodeficiency virus type-1 trans-activator of transcription (HIV-1 Tat). AB - A new method is described for the direct construction of randomly mutagenized genes by applying the polymerase chain reaction (PCR) to an oligonucleotide synthesized using doped nucleotide reservoirs. We have demonstrated the utility of this method by generating a library of mutant HIV-1 tat genes. Several arbitrarily selected, inactive tat clones were sequenced to evaluate the extent of the mutagenesis. Moreover, fourteen recombinants encoding varying levels of transcriptional trans-activator activity were isolated by transient transfection of sub-library pools into a HeLa cell line bearing an HIV-LTR-chloramphenicol acetyltransferase (CAT) reporter gene. Sequence data revealed a spectrum of alterations including nucleotide substitutions, insertions, and deletions, suggesting that mutations arose from both the doped DNA synthesis and the subsequent PCR 'rescue' of full-length product. Sequence comparison between inactive and active Tat clones revealed a selection pressure against amino-acid substitutions within the N-terminal domains of Tat, indicating the importance of this region to trans-activation competence. In addition, single and double missense mutations within the basic-rich, TAR RNA-binding domain were seen to be tolerated within active Tat clones. PMID- 1437551 TI - A spliced intron accumulates as a lariat in the nucleus of T cells. AB - The vast majority of mammalian genes are interrupted by non-coding segments of DNA termed introns. Introns are spliced out of RNA transcripts as lariat structures, and then are typically debranched and rapidly degraded. Here, we described an unusual spliced intron from the constant region of the T cell receptor-beta (TCR-beta) locus that is relatively stable in mammalian cells. This intron, IVS1C beta 1, accumulates as a set of lariat RNA structures with different length tails in the nucleus of T cells. The accumulation of this spliced intron is developmentally regulated during murine thymocyte ontogeny. The property of stability appears to be evolutionarily conserved since the human version of this intron also accumulates in T cells. The stability is selective since other spliced TCR-beta introns do not detectably accumulate in T cells. The unusual stability of this intron does not depend on T cell specific factors since non-T cells transfected with TCR-beta gene constructs also accumulate spliced IVS1C beta 1. The discovery of a mammalian intron that accumulates as a lariat in vivo provides an opportunity to elucidate mechanisms that regulate intron debranching, stability, and nuclear localization. PMID- 1437552 TI - Characterization of Chlorella virus PBCV-1 CviAII restriction and modification system. AB - A second DNA site-specific (restriction) endonuclease (R.CviAII) and its cognate adenine DNA methyltransferase (M.CviAII) were isolated from virus PBCV-1 infected Chlorella strain NC64A cells. R.CviAII, a heteroschizomer of the bacterial restriction endonuclease NlaIII, recognizes the sequence CATG, and does not cleave CmATG sequences. However, unlike NlaIII, which cleaves after the G and does not cleave either CmATG or mCATG sequences, CviAII cleaves between the C and A and is unaffected by mCATG methylation. The M.CviAII and R.CviAII genes were cloned and their DNA sequences were determined. These genes are tandemly arranged head-to-tail such that the TAA termination codon of the M.CviAII methyltransferase gene overlaps the ATG translational start site of R.CviAII endonuclease. R.CviAII is the first chlorella virus site-specific endonuclease gene to be cloned and sequenced. PMID- 1437553 TI - Analysis of chimeric mRNAs derived from the STE3 mRNA identifies multiple regions within yeast mRNAs that modulate mRNA decay. AB - In the yeast Saccharomyces cerevisiae unstable mRNAs decay 10-20 fold more rapidly than stable mRNAs. In order to examine the basis for the differences in decay rate of the unstable STE3 mRNA and the stable PGK1 and ACT1 mRNAs we have constructed and measured the decay rates of numerous chimeric mRNAs. These experiments indicate that multiple regions within yeast mRNAs are involved in modulating mRNA decay rates. Our results suggest that at least two regions within the STE3 mRNA are involved in stimulating rapid decay. One region is located within the coding region and requires sequences between codons 13 and 179. In addition, the STE3 3' UT can also function to stimulate decay. Surprisingly, the STE3 3' UT is not sufficient to accelerate the turnover of the stable PGK1 transcript unless portions of the PGK1 coding region are first deleted. These results not only identify sequences that function within yeast to stimulate mRNA turnover but also have important implications for an understanding of the basis of differences in eukaryotic mRNA decay rates. PMID- 1437554 TI - A new interaction between the mouse 5' external transcribed spacer of pre-rRNA and U3 snRNA detected by psoralen crosslinking. AB - The first cleavage in mammalian pre-rRNA processing occurs within the 5' external transcribed spacer (ETS). We have recently shown that the U3 snRNP is required for this cleavage reaction, binds to the rRNA precursor, and remains complexed with the downstream processing product after the reaction has been completed (1). Using psoralen crosslinking in mouse cell extract we have detected a new interaction between U3 RNA and the mouse ETS processing substrate and its processed product. The crosslinked sites on both U3 and ETS RNAs have been mapped by RNase H cleavage and primer extension analyses. The crosslinked sites in U3 RNA map to C5, U6, and U8. U8 lies within and C5 and U6 are adjacent to an evolutionarily conserved U3 sequence termed box A'. In the ETS the crosslinked sites are U1012 and U1013, 362 nucleotides downstream from the processing site. Although the crosslinked site is dispensable for the primary processing reaction in vitro, a short conserved sequence just 3' to the cleavage site (nucleotides 650-668) is absolutely required for crosslink formation. We conclude that the interaction between U3 RNA and the 5' ETS detected by psoralen crosslinking may play a role in subsequent step(s) of pre-rRNA processing. PMID- 1437555 TI - Cytosine nucleoside inhibition of the ATPase of Escherichia coli termination factor rho: evidence for a base specific interaction between rho and RNA. AB - The function of rho factor in transcription termination depends on interactions with nascent RNA molecules that contain unpaired cytidylate residues. We show that cytidine, as a free nucleoside, inhibits the binding of rho to lambda cro mRNA and is a competitive inhibitor of rho-ATPase activity with lambda cro mRNA as cofactor. The relative ability of various cytidine analogs and other nucleosides to inhibit the rho-RNA interaction was used to probe features responsible for the base specificity of rho action. The results suggest that rho has a specificity pocket in its polynucleotide-binding site that apparently can make H-bond interactions with the side of the cytosine ring that normally faces away from the sugar ring and that may involve a relatively close fit along the edge of the ribose ring at the C2' carbon. The nature of the complex of rho with cytidine nucleotides was analyzed further by determining whether incubation with BrCMP caused inactivation of rho ATPase. Although BrCMP could form Michaelis inhibition complexes, it did not activate rho. Rho thus lacks a diagnostic property of enzymes that make specific covalent addition complexes with pyrimidines. PMID- 1437556 TI - Molecular characterisation of a DNA ligase gene of the extremely thermophilic archaeon Desulfurolobus ambivalens shows close phylogenetic relationship to eukaryotic ligases. AB - A 3382 bp fragment containing a gene for a DNA ligase from the extremely thermophilic, acidophilic, and facultatively anaerobic archaeon (archaebacterium) Desulfurolobus ambivalens was cloned and sequenced. The deduced amino acid sequence (600 amino acids, 67619 molecular weight) showed 30-34% sequence identity with the ATP-dependent eucaryal (eukaryotic) DNA ligases of Schizosaccharomyces pombe, Saccharomyces cerevisiae, the human DNA ligase I, and with the Vaccinia DNA ligase. Distant similarity to the DNA ligases from the bacteriophages T3, T4, T6, T7 and the African swine fever virus was found, whereas no similarities were detectable to the NAD-dependent DNA ligases from the bacteria (eubacteria) Escherichia coli and Thermus thermophilus, to the ATP dependent RNA-ligase of bacteriophage T4, and to the tRNA-Ligase from S.cerevisiae. A detailed comparison of the phylogenetic relationship of the amino acid sequences of all known DNA and RNA ligases is presented including a complete alignment of the ATP-dependent DNA ligases. The in vivo-transcription initiation and termination sites of the D.ambivalens gene were mapped. The calculated transcript length was 1904-1911 nt. PMID- 1437557 TI - A repetitive DNA sequence in Paramecium macronuclei is related to the beta subunit of G proteins. AB - A repeated DNA sequence has been identified in the macronucleus of several Paramecium species. In P.tetraurelia the repeat was identified in the subtelomeric region of four randomly selected telomere clones, as well as downstream of the A type variable surface protein gene. The complete sequence of the A gene linked repeat consists of 15 tandem repeats of exactly 126 nucleotides that contain an open reading frame with significant similarity to the beta subunits of trimeric G proteins. The most striking consensus feature is the amino acid sequence DX omega WD where X is any amino acid and omega is I, L, or V spaced at precise 42 amino acids intervals. This sequence and spacing are found in G-protein beta subunits and other members of this protein motif family. Analysis of the five cloned telomeric restriction fragments showed the repeats can be found in either orientation with respect to the telomere. Poly(A) RNA transcripts containing this sequence have been identified in Paramecium tetraurelia. The conserved presence of this sequence in several species of Paramecium suggests an important physiological function, and the study of this repeat may reveal information about the evolution of this common protein motif. PMID- 1437558 TI - DeoR repression at-a-distance only weakly responds to changes in interoperator separation and DNA topology. AB - The interoperator distance between a synthetic operator Os and the deoP2O2-galK fusion was varied between 46 and 176 bp. The repression of the deoP2 directed galK expression as a function of the interoperator distance (center-to-center) was measured in vivo in a single-copy system. The results show that the DeoR repressor efficiently can repress transcription at all the interoperator distances tested. The degree of repression depends very little on the spacing between the operators, however, a weak periodic dependency of 8-11 bp may exist. PMID- 1437559 TI - In vivo stage- and tissue-specific DNA-protein interactions at the D. melanogaster alcohol dehydrogenase distal promoter and adult enhancer. AB - We performed a high resolution analysis of the chromatin structure within the regions required for distal transcription of the Drosophila melanogaster alcohol dehydrogenase gene (Adh). Using dimethyl sulfate, DNase I, and micrococcal nuclease as structural probes, and comparing chromatin structure in tissues isolated from several developmental stages, we have identified several sites of stage- and tissue-specific DNA-protein interactions that correlate with distal transcription initiation. Most were within previously identified cis-acting elements and/or in vitro protein binding sites of the adult enhancer (AAE) and distal promoter, including the TATA box. We also detected a novel stage-specific DNA-protein interaction at the Adf-2a binding site where a non-histone protein was bound to the DNA on the surface of a positioned nucleosome previously identified between the distal promoter and adult enhancer. In addition to footprints, we have also revealed stage- and tissue-specific DNA helix deformations between many of the non-histone protein binding sites. These helix distortions suggest there are interactions among the adjacently bound proteins that result in bending or kinking of the intervening DNA. The distal promoter and AAE have an accessible chromatin conformation in fat body prior to the third larval instar and many of the regulatory proteins that bind in these regions are also available before distal transcription begins. Nevertheless, the timing of DNA-protein interactions in the distal promoter and AAE suggest these proteins do not bind individually or assemble progressively as they and their binding sites become available. Instead, there appears to be a coordinated assembly of a large cooperative complex of proteins interacting with the distal promoter, the positioned nucleosome, the enhancer of the distal promoter (the AAE), and each other. PMID- 1437560 TI - Characterization of a novel T lymphocyte protein which binds to a site related to steroid/thyroid hormone receptor response elements in the negative regulatory sequence of the human immunodeficiency virus long terminal repeat. AB - We have previously identified a T lymphocyte protein which binds to a site within the LTR of the human immunodeficiency virus type 1 (HIV-1) and exerts an inhibitory effect on virus gene expression. The palindromic site (site B) recognized by this protein is related to the palindromic binding sites of members of the steroid/thyroid hormone receptor family. Here we characterize the T cell protein binding to this site as a 100 kD protein which is most abundant in T cells and which binds to site B as a 200 kD complex. This protein is distinct from other members of the steroid/thyroid hormone receptor family including the COUP protein which has a closely related DNA binding specificity. PMID- 1437561 TI - Genes for Xenopus laevis U3 small nuclear RNA. AB - Genomic Southern blots showed there are only 14 to 20 copies of U3 snRNA genes per somatic genome in Xenopus laevis, unlike the highly repetitive, tandem arrangement of other snRNA genes in this organism. Sequencing of two U3 snRNA genes from lambda clones of a genomic library revealed striking similarity upstream, but much more divergence downstream. Consensus motifs common to other U snRNA genes were also found: a distal sequence element (DSE, octamer motif at 222 to -215), a proximal sequence element (PSE, at -62 to -52) and a 3' Box (15 or 16 bp downstream of the U3 genes). The DSE of mammals also has an inverted CCAAT motif specific for U3 snRNA genes, and we find this is conserved in the amphibian U3 snRNA genes. The Xenopus inverted CCAAT motif is exactly one helical turn further upstream of the octamer motif than its mammalian counterpart, suggesting interaction of putative transcription factors bound to these motifs. Mutation of the inverted CCAAT motif and part of an adjacent Sp1 site greatly depresses transcription of the mutant U3 snRNA gene in Xenopus oocytes, implying a role in transcriptional efficiency. Electrophoretic mobility shift assays implicate transcription factor binding to this region. PMID- 1437563 TI - Crystal structure of a B-DNA dodecamer containing inosine, d(CGCIAATTCGCG), at 2.4 A resolution and its comparison with other B-DNA dodecamers. AB - The crystal structure of the dodecamer, d(CGCIAATTCGCG), has been determined at 2.4 A resolution by molecular replacement, and refined to an R-factor of 0.174. The structure is isomorphous with that of the B-DNA dodecamer, d(CGCGAATTCGCG), in space group P2(1)2(1)2(1) with cell dimensions of a = 24.9, b = 40.4, and c = 66.4 A. The initial difference Fourier maps clearly indicated the presence of inosine instead of guanine. The structure was refined with 44 water molecules, and compared to the parent dodecamer. Overall the two structures are very similar, and the I:C forms Watson-Crick base pairs with similar hydrogen bond geometry to the G:C base pairs. The propeller twist angle is low for I4:C21 and relatively high for the I16:C9 base pair (-3.2 degrees compared to -23.0 degrees), and the buckle angles alter, probably due to differences in the contacts with symmetry related molecules in the crystal lattice. The central base pairs of d(CGCIAATTCGCG) show the large propeller twist angles, and the narrow minor groove that characterize A-tract DNA, although I:C base pairs cannot form the major groove bifurcated hydrogen bonds that are possible for A:T base pairs. PMID- 1437562 TI - The Crithidia fasciculata CRK gene encodes a novel cdc2-related protein containing large inserts between highly conserved domains. AB - A gene (CRK) encoding a cdc2-related protein has been identified in the trypanosomatid Crithidia fasciculata. CRK has a high degree of sequence identity with the human cdc2 gene and contains the sixteen amino acid PSTAIR motif, characteristic of p34cdc2 protein-serine/threonine kinases, with four amino acid substitutions in the motif. In addition, two inserts of more than sixty amino acids have been found between conserved domains of this putative protein serine/threonine kinase. CRK is a single copy gene and is expressed on a 3.8 kb mRNA. Anti-CRK antibodies detect a 53kDa protein in extracts of C.fasciculata in agreement with the size predicted from the nucleotide sequence of the cloned gene. These antibodies also recognize proteins of 48 and 60 kDa in extracts of the trypanosomatid Leishmania tarentolae. Antibodies against the human PSTAIR peptide detect the p34cdc2 protein in human nuclear extracts but fail to detect a 34 kDa protein in C.fasciculata extracts. These results suggest that novel higher molecular weight forms of the cdc2 protein family may be involved in cell cycle control in trypanosomes. PMID- 1437564 TI - The basic RNA-binding domain of HIV-2 Tat contributes to preferential trans activation of a TAR2-containing LTR. AB - Human immunodeficiency viruses HIV-1 and HIV-2 encode a Tat protein that trans activates the respective viral genome through RNA targets (TAR1 and TAR2). Tat-1 and Tat-2 have considerable homology. However, an interesting biological observation has been that Tat-1 activates the HIV-1 and HIV-2 LTRs equally while Tat-2 activates the former, in comparison to the latter, poorly. Here, we present evidence that it is the TAR2 RNA target together with the basic RNA-binding protein domain of Tat-2 that dictate this non-reciprocity in trans-activation. PMID- 1437565 TI - Structure of a gene in the dipteran Chironomus tentans encoding a yeast ribosomal YL10 protein homologue. PMID- 1437566 TI - Nucleotide sequence of cDNA of the tobacco mosaic virus RNA isolated in Korea. PMID- 1437567 TI - Primary sequence of the human ribosomal protein L37a. PMID- 1437568 TI - Streptomyces contain a 7.0 kDa cold shock like protein. PMID- 1437569 TI - DNA base sequence variability in katF (putative sigma factor) gene of Escherichia coli. PMID- 1437570 TI - The common bean chloroplast trnH (GUG) gene and its eukaryotic putative promoter elements. PMID- 1437571 TI - ASF alternative transcripts are highly conserved between mouse and man. PMID- 1437572 TI - VDE endonuclease cleaves Saccharomyces cerevisiae genomic DNA at a single site: physical mapping of the VMA1 gene. PMID- 1437573 TI - E1a-responsive mammalian host/vector system for the stable high-level expression of secreted proteins. PMID- 1437574 TI - Extension product capture improves genomic sequencing and DNase I footprinting by ligation-mediated PCR. PMID- 1437575 TI - Genetic analysis using fingernail DNA. PMID- 1437576 TI - Simplified DGGE in a horizontal electrophoresis system. PMID- 1437577 TI - Parentage analysis using RAPD PCR. PMID- 1437579 TI - Persistence. PMID- 1437580 TI - Challenging misperceptions about nurses' moral reasoning. AB - Discussions in the nursing literature about the usefulness of Kohlberg's theory of moral reasoning for women and nurses, and assertions about the level of moral reasoning scores of nurses have been clouded by inaccuracies and misperceptions. In this article, theoretical and measurement issues related to moral reasoning are clarified and a critical review of the literature is provided about the moral reasoning of nursing students and nurses as measured by the Defining Issues Test (DIT). The review indicates the need for greater rigor in studies of moral reasoning among nurses and the need for accuracy in interpreting and reporting moral reasoning scores. The data show that the moral reasoning of nurses, like that of other groups, tends to increase with formal education. Nurses' scores are usually comparable to, and sometimes higher than, scores of their academic peers. PMID- 1437581 TI - Validation of the PRQ85 social support measure for adolescents. AB - The purposes of this study were to factor analyze the 25-item Personal Resource Questionnaire (PRQ) 85-Part II, a social support measure, and to establish construct validity for the instrument among adolescents by testing two hypotheses derived from theoretical propositions by Weiss (1974) concerning the relational provisions of social support. The purposes were accomplished using a sample of 325 adolescents, aged 12 to 21. According to the criteria used in this study, a four-factor structure, resulting from a principal components analysis with an oblique rotation, best represented the multidimensionality of the PRQ85-Part II in adolescents. A second-order factor analysis indicated that the four first order factors correlated to form one factor, which consisted of 17 items and was labeled Perceived Social Support. Evidence in support of construct validity for both the 17-item and 25-item PRQ85-Part II was provided by statistically significant correlations found between the two scales and the theoretically relevant variables of perceived health status and symptom patterns. The contributions of this study to the psychometric properties of the PRQ85-Part II can be used in future research concerning social support in adolescents. PMID- 1437582 TI - The HOME scale: the influence of socioeconomic status on the evaluation of the home environment. AB - Caldwell's Home Observation for Measurement of the Environment (HOME) was developed to provide specific and sensitive information about the home and maternal environment as a stimulus to infant learning and development. The use of the HOME scale was examined in a sample of 118 middle- and lower-income mothers and their low-birth-weight (LBW) or very-low-birth-weight (VLBW) infants. The analysis of data demonstrated limited variability in the HOME scale total scores within each income group, and income alone was found to account for 41% of the variance in the sample. These findings raise questions about the effectiveness of the HOME scale in making useful discriminations about family functioning within an income group. PMID- 1437578 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1437583 TI - Concurrent validity of a new instrument for measuring nutritive sucking in preterm infants. AB - The purpose of this study was to examine the concurrent validity of the Whitney strain gage for the measurement of nutritive sucking in preterm infants. Ten preterm infants were studied continuously during at least one entire bottle feeding per week, from admission into the study until discharge from the nursery. Sucking was measured simultaneously by an adapted nipple and the Whitney gage. The two instruments were compared on the following measures: number of sucking bursts, number of sucks per burst, and duration of bursts and pauses between bursts. Total percent agreement for the occurrence of a sucking burst was 99.3% (K = .99). Sucks per burst varied from 2 to 113, with 89.3% of the pairs of sucking bursts differing by < or = 1 suck per burst. The mean absolute difference between the two instruments for the duration of sucking bursts and pauses was .64 s and .72 s, respectively. These results demonstrate the concurrent validity of the Whitney gage for measurement of sucking events in preterm infants. PMID- 1437584 TI - Instrument development: cardiac diet and exercise self-efficacy. AB - Self-efficacy has been documented as a strong predictor of health behaviors. Unfortunately, availability of reliable and valid measures of self-efficacy for a range of health behaviors is still limited. This study validated two measures of cardiac risk factor self-efficacy: the Cardiac Diet Self-Efficacy Instrument (CDSEI) and the Cardiac Exercise Self-Efficacy Instrument (CESEI). A sample of 370 cardiac rehabilitation participants provided data for principal factor analyses showing the unidimensionality of each instrument. Known groups construct validity was supported by a comparison of CDSEI and CESEI scores for cardiac rehabilitation participants and marathon runners. The value of CDSEI and CESEI scores in predicting subsequent exercise and diet performance was demonstrated with a third group of cardiac rehabilitation participants. Stability and internal consistency estimates in the .80s and .90s, respectively, support the scales' reliabilities. PMID- 1437585 TI - Finishing first grade: a study of school achievement in very-low-birth-weight children. AB - Factors that influence school achievement in very-low-birth-weight (< 1,500 g) children were investigated at the completion of first grade. The subjects were 71 children and their primary caregivers. Thirty-nine children were very low birth weight (VLBW) and 32 were normal birth weight (NBW). After controlling for birth weight status, over one third of the variance in children's school achievement was accounted for by the age of the child's mother when she began childbearing. Birth weight status accounted for significant amounts of variance in information processing skills. Significantly more children in the VLBW group required special services and fewer were promoted to second grade, although the difference was not significant. PMID- 1437586 TI - Patients' reactions to completion of adjuvant breast cancer therapy. AB - Thirty-eight women with breast cancer were studied to determine the psychological distress they experienced at the completion of adjuvant treatment. Measures were completed at the start of adjuvant chemotherapy, one week after chemotherapy was completed, and following completion of radiotherapy. Approximately 30% of the women reported the termination of treatment was upsetting. For the group as a whole, depression scores decreased significantly from the first to the last measurement. Those who were most upset by termination of treatment had been more depressed since the onset of treatment, tended to view their illness as chronic rather than acute, and had more side effects during their last cycle of chemotherapy. Some women stated they were upset by the termination of treatment per se, but many other problems were reported including side effects that had continued after treatment ended. PMID- 1437588 TI - Re: 'More than skin deep' (July/August editorial) PMID- 1437587 TI - Symptoms of preterm labor and self-diagnostic confusion. AB - The purpose of this study was to learn how women experiencing preterm labor come to know a health deviation exists, and what they do when faced with such a problem. Grounded theory methodology was used as the research approach. Extensive interviews were conducted with 28 women about their care-seeking experiences with preterm labor. Ambiguous symptoms, absence of a meaningful label to attach to symptoms, and the context of pregnancy with its expected discomforts come together to create a situation of diagnostic confusion. Appropriate action to take in response to the diagnostic confusion is not self-evident. Deliberate and protracted efforts to make sense of and deal with symptoms of preterm labor are attempted. Making sense consists of three subprocesses: comparing, gathering data, and seeking information. Strategies used to deal with the symptoms include self-treating, ignoring, positive thinking, and waiting. Recourse to a professional is used as the strategy of last resort when symptoms can no longer be contained. PMID- 1437589 TI - Re: 'The role of nursing research committees'. PMID- 1437590 TI - Perinatal factors and infant temperament: a collaborative approach. PMID- 1437592 TI - Edith Cavell: traitor or savior? PMID- 1437591 TI - Standardization of the visual analogue scale. PMID- 1437593 TI - Research module R4: the real world of research. Part (i): Funding and organising research. PMID- 1437594 TI - The joys of working in a climate of innovation and enthusiasm. PMID- 1437595 TI - A will to choose. PMID- 1437596 TI - Healthy states? PMID- 1437597 TI - Private worries. PMID- 1437598 TI - A lousy plan? PMID- 1437599 TI - Abuse of trust. PMID- 1437600 TI - Life on Easy Street--rehabilitation. PMID- 1437601 TI - Unconditional discharge? PMID- 1437602 TI - Plugging the gap--diabetes. PMID- 1437603 TI - Handling patients--mind your back. PMID- 1437604 TI - Polio's still lethal punch--care study. PMID- 1437605 TI - Accredit where it's due--nursing development units. PMID- 1437606 TI - Strategies for closure. PMID- 1437607 TI - United front. PMID- 1437608 TI - Post-registration education in three fields of clinical practice. AB - This paper describes some empirical findings about the take-up of post registration education by a substantial sample of clinical practitioners in three fields of practice--mental illness nursing, mental handicap nursing and midwifery. Some implications of the results are discussed in the context of the UKCC PREPP Report recommendations, as a contribution to the current debate about their implementation. PMID- 1437609 TI - Spirituality needs more attention. PMID- 1437610 TI - Computer takes note of shift preferences. PMID- 1437612 TI - Health visitors. Assistants for the future. PMID- 1437611 TI - Drug compliance after leaving hospital. PMID- 1437613 TI - Health visitors. Preventing postnatal illness. PMID- 1437614 TI - Health visitors. In a class of their own. PMID- 1437615 TI - Professional development module. P10: Delivery of care. Part (i): The nurse/client relationship. PMID- 1437616 TI - Government rules are penalising Project 2000 students financially. PMID- 1437618 TI - Quality care. PMID- 1437617 TI - Prisoner in Baghdad. Interview by Amanda Tattam. PMID- 1437619 TI - Gagging guidelines? PMID- 1437620 TI - Nipped in the bud? PMID- 1437621 TI - Cutting the cake. PMID- 1437622 TI - The right of refusal? PMID- 1437623 TI - Promoting prevention. PMID- 1437625 TI - A time to live or a time to die? Euthanasia. PMID- 1437624 TI - Making sense of electrosurgery. PMID- 1437626 TI - Passive taboos. Euthanasia. PMID- 1437627 TI - Making a point of contact. Mental health. PMID- 1437628 TI - A way with words--nursing narrative. PMID- 1437629 TI - 'Look after me'--nursing narrative. PMID- 1437630 TI - A broken promise--nursing narrative. PMID- 1437631 TI - Computers: the CARM approach (Computer Assisted Relapse Management Program). PMID- 1437632 TI - Informing potential donors' families. PMID- 1437633 TI - Asian women and the health service. PMID- 1437634 TI - Infections control--for safety's sake. PMID- 1437635 TI - Infection control--lessons to be learnt. PMID- 1437636 TI - Infection control--a pivotal role. PMID- 1437637 TI - Children with HIV often survive. PMID- 1437638 TI - Pioneer AIDS campaigner reveals he has illness and wins ovation. PMID- 1437639 TI - Women with AIDS die early as symptoms are ignored. PMID- 1437640 TI - Natural dietary ingredients (oats and alfalfa) induce covalent DNA modifications (I-compounds) in rat liver and kidney. AB - Mammalian tissue DNA has recently been found, via 32P postlabeling, to contain complex profiles of age-dependent bulky carcinogen adductlike covalent modifications, which have been termed I-compounds, referring to their apparent indigenous origin without exposure to exogenous carcinogens. I-compound patterns are highly species, sex, tissue, and diet specific. As shown here, the presence of certain plant ingredients in diet, i.e., ground oats and alfalfa meal, significantly contributed to the formation of these DNA derivatives. Six groups of weanling female Sprague-Dawley rats were fed one of the following diets for three months: a natural ingredient diet containing neither oats nor alfalfa (Wayne MRH 22/5 Rodent Blox), Wayne diet supplemented with oats or alfalfa or both, a purified semisynthetic diet (AIN-76A), and AIN diet supplemented with oats. The natural ingredient diet produced more complex patterns and higher levels of I-compounds than purified diet in both liver and kidney DNA. Supplementation of either diet with oats elicited the formation of four additional oats-specific I-compounds in liver DNA. Oats and alfalfa, individually and in combination, tended to significantly raise nonpolar and diminish polar I compound levels. To determine whether the oats-related extra spots were derived from mycotoxin contamination, two groups of rats were fed either Wayne diet or Wayne diet containing zearalenone (0.05 mg/kg) for three weeks. Zearalenone significantly increased the uterine weight but did not induce any DNA adduct formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437641 TI - Prolongation of survival in retrovirally induced T cell lymphoma by dietary omega 6 fatty acid. AB - C57BL/Ka mice were fed diets rich in omega 3 or omega 6 polyunsaturated fatty acids and inoculated with the thymic lymphoma-inducing retrovirus RadLV. Mice receiving the omega 3 diet died significantly sooner than those receiving the omega 6 diet. Of the three known mechanisms by which fatty acids can exert antiviral activity, namely, modification of membrane fluidity, modulation of immune response, and synthesis of metabolites with antiviral activity, the first two can be eliminated in the model under study. It is therefore concluded that differences in survival are due to fatty acid metabolites with distinct antiviral activities. PMID- 1437642 TI - Vitamin E inhibition of lipid peroxidation and ethanol-mediated promotion of esophageal tumorigenesis. AB - Promotion of chemically induced esophageal cancer by ethanol may include the generation of highly reactive free radicals and thus may be preventable by the antioxidant vitamin E. In the present study, female C57BL/6 mice received N nitrosomethylbenzylamine (NMBzA, 0.2 mg/kg ig) three times a week for three weeks. After this esophageal carcinogenic treatment, mice were fed a nutritionally adequate liquid diet with 30% of the calories supplied by ethanol or an isocaloric carbohydrate with or without supplemental alpha-tocopherol (142 mg/kg diet). As a marker of in vivo lipid peroxidation, exhaled ethane was collected and measured 24 hours "before" the mice were killed after 20 weeks of dietary treatment. Hepatic malondialdehyde, lipid fluorescence, and conjugated dienes were determined as markers of products of lipid peroxidation and serum aminotransferases as indexes of liver toxicity. Hepatic liver concentrations of vitamins A and E and the size and frequency of esophageal tumors were also assessed. Ethanol consumption after NMBzA administration significantly increased (p less than 0.05) the size and frequency of esophageal tumors. These ethanol promoted effects were accompanied by increases in indexes of in vivo and accumulated products of lipid peroxidation. Similarly treated animals that received supplemental dietary vitamin E showed significant reductions (p less than 0.05) in mean tumor size and frequency of tumors as well as a decrease in the indexes of hepatic lipid peroxidation. The results suggest that promotion of NMBzA-induced esophageal tumors by ethanol may in part result from increased lipid peroxidation and that vitamin E reduces carcinogenicity of NMBzA or ethanol promoter effects by inhibiting lipid peroxidation. PMID- 1437643 TI - Effects of a long-chain fatty amine on mammary carcinogenesis induced in female Sprague-Dawley rats by DMBA. AB - Reports that protein kinase C is inhibited by sphingosine and other long-chain amines and the suggestion that promotion of mammary carcinogenesis by dietary fat is mediated by protein kinase C prompted us to investigate the effects of a long chain amine, 1-octadecylamine, on mammary carcinogenesis induced by 7,12 dimethylbenz[a]anthracene in rats fed a high-fat diet. Rats fed the amine sulfate at a level of 0.01% in a semipurified diet containing 20% corn oil developed more tumors than those fed the high-fat diet alone, although body weight gain was inhibited slightly. Rats fed the amine sulfate at 0.1% of the diet developed very few tumors compared with those fed either the high-fat diet or a low-fat diet containing 5% corn oil. At the higher level, the C18 amine also caused a marked inhibition of body weight gain. PMID- 1437644 TI - Dietary intake and risk of lung cancer in women who never smoked. AB - A case-control study was conducted to examine the influence of dietary factors on the risk of developing lung cancer among women who have never smoked cigarettes. This study included 124 cases of histologically confirmed carcinoma of the lung and 263 community-based controls. Dietary data were collected utilizing the reduced version of the National Cancer Institute (Block) food frequency questionnaire. The results of this analysis, adjusted for age, education, and total calories, indicated a strong protective effect associated with total vegetable consumption and intake of carotene. Individuals in the highest quartile of vegetable consumption experienced the greatest decreased risk with an odds ratio (OR) of 0.2, [confidence interval (CI) 0.1-0.5]. The effect of all vegetables combined was greater than that of green and yellow vegetables alone (highest quartile OR 0.4, CI 0.2-0.7). Similarly, the protective effect of total carotene (highest quartile OR 0.3, CI 0.1-0.6) was somewhat greater than that of beta-carotene alone (highest quartile OR 0.4, CI 0.2-0.8). Retinol intake was not associated with a decreased risk of lung cancer in our population. There was an inverse association between lung cancer risk and vitamin C intake, which was not significant, although a statistically significant trend was noted. PMID- 1437645 TI - Diet and prognosis of breast cancer. AB - The relationship between the occurrence of breast cancer and dietary intake, in particular a high-fat diet, has attracted much attention in recent years. In addition, the prognosis of breast cancer patients on the basis of dietary intake is also an interesting subject. The present study utilized breast cancer patients whose dietary intake was carefully assessed about one decade previously in a case control study to determine whether dietary intake was indeed related to the patients' prognosis. The study included 212 patients who underwent a surgical operation between 1975 and 1978. They were followed-up until 1987, and a total of 47 breast cancer deaths were certified. The 5- and 10-year relative survival rates were 78.5% and 75.3%, respectively. The older patients tended to ingest smaller amounts of all nutrients, except animal fat from fish. Height was significantly correlated with total animal protein intake, whereas there was no significant correlation between body mass index and intake of any nutrient. Although the age-adjusted mean values of the nutrient intakes, other than vegetable fat, decreased with advancing stage, the differences were statistically insignificant. The results of multivariate analyses, in which some confounding factors (e.g., clinical stage) were adjusted using a proportional hazards model, showed that all hazards ratios in each nutrient were close to unity, and no dose response relationship was seen. The present investigation did not provide any support for the hypothesis that a high-fat diet is a survival determinant for breast cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437646 TI - Mammary cancer prevention by regular garlic and selenium-enriched garlic. AB - The anticarcinogenic activities of regular (soil-grown) garlic and selenium enriched garlic (cultivated in the greenhouse) were evaluated using the 7,12 dimethylbenz[a]anthracene-(DMBA) induced mammary tumor model in rats. In Experiment 1, milled regular garlic powder was added to the basal AIN-76A diet at 20 g/kg. The results from different schedules of supplementation suggested that a continuous treatment, which started before DMBA and persisted for the entire duration of the study, was most effective in tumor suppression. In Experiment 2, selected allyl group-containing sulfides that are normal constituents of garlic extract were given by gavage in three single doses immediately before DMBA. Several structurally related compounds were found to be protective during the initiation phase in the mammary cancer model. Although the present study was not designed specifically to elucidate the structure-activity relationship with respect to sulfur chain length or alkyl versus alkenyl substitution, our data showed that diallyl disulfide was more active than diallyl sulfide or allyl methyl sulfide. In Experiment 3, the anticarcinogenic activity of selenium enriched garlic (containing 150 ppm Se dry weight from growth in a selenium fertilized medium) was compared with that of regular garlic as well as selenite. Animals given the selenium-enriched garlic (final concentration 3 ppm Se in the diet) developed the fewest mammary tumors. Tissue selenium levels, however, were lower in these animals than in those fed the same amount of selenium from selenite. Our study demonstrated the feasibility of achieving cancer prevention with the use of a selenium-rich food system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437647 TI - Antimutagenic and anticarcinogenic effects of carotenoids and dietary palm oil. AB - Four carotenoids, canthaxanthin, beta-carotene, 8H-apo-beta-carotenal, and 8'-apo beta-carotene methylester were tested for their ability to suppress the mutagenicity of 1-methyl-3-nitro-1-nitrosoguanidine and benzo[a]pyrene (BP) in Salmonella typhimurium tester strain TA 100. The anticarcinogenic efficacy of the four carotenoids was further assessed in the BP-induced forestomach tumor model in female Swiss mice. The effect of dietary palm oil was also examined in BP induced neoplasia in the female Haffkine Swiss mouse strain. Canthaxanthin, beta carotene, 8'-apo-beta-carotenal, and 8'-apo-beta-carotene methylester showed a dose-dependent decrease in the mutagenicity compared with 1-methyl-3-nitro-1 nitrosoguanidine and BP in strain TA 100. In the BP-induced forestomach tumor model, all four carotenoids showed a similar significant anticarcinogenic effect. Dietary administration of palm oil showed a dose-dependent antitumor activity in the animals. Our results show that the intrinsic antimutagenic and anticarcinogenic properties of the carotenoids are not significantly influenced by their conversion to vitamin A. PMID- 1437648 TI - Differences in dietary intake with smoking, alcohol, and education. AB - Differences in the frequency of consumption of 30 selected foods and in the estimated intake of total calories and selected nutrients in relation to alcohol drinking, tobacco smoking, and education were described using information obtained from 1,774 controls of a case-control study of digestive tract cancers conducted in northern Italy. Heavy alcohol consumption, tobacco smoking, and lower level of education were associated with a diet poorer in several aspects, including lower consumption of fresh fruit and green vegetables and higher intake of specific indicator foods, such as sausages and canned meat. For instance, the mean number of portions of fresh fruit per week was 10.5 among male nondrinkers vs. 9.0 among heavy drinkers, 10.4 among male nonsmokers vs. 8.1 among heavy smokers, and 8.8 in less educated individuals vs. 10.7 among those more educated. Consequently, intake of beta-carotene, ascorbic acid, and calcium tended to be inversely related to alcohol and tobacco and directly related to education. Most associations were stronger in males, for whom alcohol consumption was also more common in less educated individuals. Calorie intake was directly related to alcohol consumption, largely reflecting calories provided by alcohol itself. However, alcohol drinking was also directly related to fat consumption. In both sexes, there was a strong positive correlation between cigarette smoking and coffee drinking. These results provide quantitative documentation that alcohol drinking, tobacco smoking, and education, three of the major determinants of cancer risks, were also correlates of dietary patterns and, hence, may exert an important confounding or modifying effect on the diet and cancer relationship. PMID- 1437649 TI - Influence of dietary fat intake on local recurrence and progression of metastases arising from MDA-MB-435 human breast cancer cells in nude mice after excision of the primary tumor. AB - This study was performed to evaluate the effect of dietary fat on the recurrence and metastasis of human breast cancer solid tumors growing in nude mice after surgical excision of the primary tumor. Female nude mice were fed either a high- (23% corn oil) or a low-fat (5% corn oil) diet, and 7 days later 1 x 10(6) MDA-MB 435 human breast cancer cells were injected into a thoracic mammary fat pad. Tumors at the injection site grew more rapidly in the animals fed the high-fat diet. Nineteen of 30 animals in each dietary group had tumors with a surface are > or = 1 cm2 within 10 weeks of injection, at which point the tumors were excised and the animals were followed for another eight weeks. Tumors recurred at the excision site in 8 of 19 animals fed the high-fat diet and in 9 of 19 animals fed the low-fat diet; however, the growth rate was more rapid in the group fed the high-fat diet. Lung metastases occurred with similar frequency in the two groups with local recurrences, but with a positive correlation between recurrent tumor weight (greater in the animals fed the high-fat diet) and the severity of lung metastatic involvement. In the mice without recurrence, 4 of 11 (36%) animals in the group fed the high-fat diet had macroscopic lung metastases compared with only one mouse, with minimal involvement, in the group fed the low-fat diet. PMID- 1437650 TI - Reliability of dietary information from surrogate respondents. AB - A self-administered food frequency questionnaire was included as part of a case control study of breast cancer in 1980-82. In 1986-87, a second food frequency questionnaire was sent to surviving cases and husbands of deceased cases; 30 spouses (86% response rate) and 263 surviving cases (88% response rate) returned questionnaires. The dietary questions concerned consumption of specific food items by the case before diagnosis of breast cancer. Missing values were less common in the second questionnaire; there was no significant difference in missing values between surviving cases and spouses of deceased cases. Kappa statistics comparing responses in the first and second questionnaires were significantly lower for spouses of deceased cases than for surviving cases. Reported level of confidence by the husbands regarding knowledge about their wives' eating habits did not influence the kappa statistics or the frequencies of missing values. The lack of good agreement has important implications for the use of proxy interviews from husbands in retrospective dietary studies. PMID- 1437651 TI - The reproducibility of a food frequency questionnaire among controls participating in a case-control study on cancer. AB - This study was designed to test the reproducibility of a food frequency questionnaire used in a population-based case-control study on diet and pancreatic cancer. Repeat questionnaires covering the same time period were obtained using 63 male and female population controls, 35-79 years of age. For selected food items included in the case-control study, the attenuation of the odds ratios due to random error was estimated. Using 54 male and female population controls, 35-79 years of age, we conducted a second study to examine the agreement between original and repeat interviews when the time interval between interview and the period of interest was constant. In the first study, the median correlation coefficient was 0.72 for foods (ranging from 0.36 and 0.59 for subgroups of vegetables to 0.96 for alcoholic beverages) and 0.77 for nutrients (ranging from 0.62 for beta-carotene to 0.85 for energy and 0.91 for ethanol). In the second study, the median correlation coefficient was 0.68 for foods (ranging from 0.28 for eggs to 0.87 for alcoholic beverages) and 0.75 for nutrients (ranging from 0.48 for beta-carotene to 0.76 for energy). We conclude that for most items the agreement between original and repeat estimates was moderate (r > 0.50) to high (r > 0.70). Moderate agreement was found for 28 of 33 food items (85%) and for all 21 nutrient items (100%) and high agreement for 19 of 33 of food items (56%) and 15 of 21 nutrient items (71%). In the second study, agreement was somewhat lower but closely paralleled the results of the first study. On average, random error presumably attenuated most of the observed diet cancer relationships only moderately; i.e., an observed odds ratio of 1.5 and a correlation coefficient of 0.70 yield an unattenuated odds ratio of 2.1. PMID- 1437652 TI - Bile salt/acid induction of DNA damage in bacterial cells: effect of taurine conjugation. AB - Bile salts and acids have been implicated in the etiology of colon cancer, possibly through their ability to cause DNA damage. Taurine-conjugated and nonconjugated forms of three bile salts and one bile acid were tested for DNA repair-inducing potential and for cellular toxicity in a recently developed Escherichia coli chromotest system. The taurine-conjugated forms of sodium deoxycholate and lithocholic acid had reduced ability to induce DNA repair. Also the taurine-conjugated form of lithocholic acid had a reduced lethal effect. These observations suggest that the biotransformation step, whereby bacteria in the intestine remove the taurine added to bile salts in the liver, may be significant in the etiology of colon cancer. PMID- 1437653 TI - Humoral and cellular immune functions are not compromised by the anticarcinogenic Bowman-Birk inhibitor. AB - Previous studies have demonstrated that the soybean-derived Bowman-Birk protease inhibitor (BBI) is effective as a cancer chemopreventive agent in several animal model systems. Proteases represent a key component of several aspects of immune function; therefore the immune system is a primary target for potential toxicity. The present investigation examines the effect of dietary and intraperitoneally administered BBI on antibody response to keyhole limpet hemocyanin and delayed type hypersensitivity response to dinitrochlorobenzene. Primary antibody response was not altered by BBI treatment; however, an elevated secondary response was observed in animals receiving dietary BBI at two weeks of age. This effect was not observed at later time points. No change in delayed-type hypersensitivity response was observed in any of the treatment groups. PMID- 1437654 TI - Fecal ammonia in patients with adenomatous polyps and cancer of the colon. AB - The correlation between high intakes of protein and high incidence of human colonic cancer is unexplained. Appreciable amounts of ammonia are generated in the large bowel through bacterial degradation of proteins and peptides, and experimental studies indicate that ammonia may select for neoplastic growth. Fecal concentrations of ammonia did not differ among 17 patients with former colonic adenomas [40.6 +/- 4.5 (SE) mM], 17 patients with former colonic cancer (51.4 +/- 3.9 mM), and 16 healthy controls (46.4 +/- 6.1 mM). By use of an in vitro fecal incubation system, possible alterations in bacterial fermentation and formation of ammonia were investigated. Fecal suspensions were incubated for 6 and 24 hours with and without addition of fermentable substrates (ispaghula husk, wheat bran, albumin, and glucose; 10 mg/ml). The in vitro production of ammonia in unsupplemented fecal homogenates from both groups of patients was comparable with the production found in homogenates from healthy controls, and the response to fermentable substrates was similar in all three groups. Addition of albumin caused a marked increase in the production of ammonia, and addition of glucose increased bacterial assimilation of ammonia considerably. These well-known characteristics of bacterial metabolism of ammonia apparently did not differ between healthy individuals and patients investigated more than three months after colonoscopic polypectomy or colonic cancer resection. PMID- 1437655 TI - Biodistribution of ellagic acid and dose-related inhibition of lung tumorigenesis in A/J mice. AB - Ellagic acid (EA), derived from fruit ellagitannins, is known to be antimutagenic and anticarcinogenic in various animal tumor models. In this study, EA at a dose of 4 g/kg diet inhibited multiplicity of tumors induced by 4-(methylnitrosamino) 1-(3-pyridyl)-1-butanone (NNK) in A/J mice by 54%. This inhibition was dose related between 0.06 and 4.0 g/kg diet. In contrast, two related compounds, esculin and esculetin, had no effect on lung tumorigenesis. The biodistribution of EA was studied as a function of dose and time after gavage of EA. The levels of EA in the lung were directly proportional to the dose of EA between 0.2 and 2.0 mmol. The maximum level of EA, corresponding to 21.3 nmol/g, was observed 30 minutes after gavage with 2.0 mmol of EA/kg body wt, which corresponds to only 70 ppm of the administered dose. The levels in liver tissues were 10-fold lower and reached a maximum 30 minutes after gavage. At this interval, the blood level of EA was 1 nmol/ml. The inclusion of EA in cyclodextrin doubles the level of EA in lung tissues. These results demonstrate that EA localizes preferentially in lung tissues and confirm that EA administered orally can inhibit lung tumorigenesis. PMID- 1437656 TI - The carcinogenicity of some antimalarial drugs using the Egyptian toad Bufo regularis as a biological test animal. AB - Feeding Egyptian toads (Bufo regularis) with chloroquine and primaquine separately induced tumor formation in 14% and 19% of the animals, respectively. When chloroquine and primaquine were given in combination, the tumor incidence increased to 23.5%. Chloroquine feeding resulted in tumors located in the liver (lymphosarcomas) and primaquine in tumors in the kidney (histiocytic sarcomas). Toads fed chloroquine plus primaquine developed tumors in the liver, kidney, lung, and urinary bladder, and all the tumors were diagnosed as histiocytic sarcomas. It is speculated that one or more metabolites of chloroquine and primaquine (e.g., quinone) may be responsible for tumor induction in the toads. PMID- 1437657 TI - Alcohol consumption and the etiology of colorectal cancer: a review of the scientific evidence from 1957 to 1991. AB - The relationship between alcohol consumption and colorectal cancer in humans has been examined in 52 major studies in the past 35 years. An association was found in five of the seven correlational studies. An elevated risk was found in about half of the 31 case-control studies and, of these, in 9 of the 10 studies using community controls but in only 5 of the 17 studies using hospital controls (p = 0.008), suggesting that the absence of association when hospital controls are used is due to a high prevalence of alcohol consumption/alcohol-related illness in the hospital controls. Of the 14 cohort studies, an association with alcohol was found in 10, while in 3 of the 4 cohort studies in which an association was not found the alcohol data obtained were somewhat restricted. A positive dose response effect was found in two of three cohort studies and in all four case control studies with community controls in which this effect was examined. In both case-control and cohort studies, the association was found for females and males and for colon and rectal cancer. When the type of alcohol consumed was examined separately, beer was the principal type of at-risk alcoholic beverage, with much less risk for spirits and least risk for wine. Statistically significant elevations of risk were more often found in males than in females and slightly more frequently for rectal than for colon cancer and were related almost entirely to beer, rather than to wine or spirit, consumption. The alcohol risk was independent of the dietary risk in those studies that controlled for this factor. There was some confirmatory evidence for alcohol augmentation in rodent models of chemically induced carcinogenesis in six of nine studies. The hypotheses of alcohol as a direct and specific colorectal carcinogen include increased mucosal cell proliferation, the activation of intestinal procarcinogens, and the role of unabsorbed carcinogens, particularly in beer. Also, five of six other human studies showed an association between alcohol/beer consumption and adenomatous polyps, consistent with the hypothesis that alcohol stimulates the colorectal mucosa. General or indirect carcinogenic effects of alcohol include immunodepression, activation of liver procarcinogens, and changes in bile composition, as well as nitrosamine content of alcoholic beverages and increased tissue nitrosamine levels. With alcohol/beer consumption, the overall conclusion on present evidence is that alcohol, particularly beer consumption, is an etiologic factor for colon and rectal cancer for females and males.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1437658 TI - Factors to be considered for assignment in inservice education. PMID- 1437660 TI - Family physician. PMID- 1437659 TI - The WHO golden rules for safe food preparation. PMID- 1437661 TI - Women, health and development. PMID- 1437662 TI - Management skills in nursing. VIII. A.C.E. programme of TNAI--a report. PMID- 1437663 TI - Health status of nurses and yoga. IV. Experiment and results. PMID- 1437664 TI - Consumers' participation to promote health. PMID- 1437665 TI - Use of a new fallback function to prevent endless-loop tachycardias: first clinical results. The Investigators of the Multicenter Study. AB - The methods used for preventing endless-loop tachycardias (ELTs) most often consist of initiating a long postventricular atrial refractory period (PVARP) with the sensing of every event likely to induce ELTs, such as sensed premature ventricular contractions (PVCs). A new fallback function may be useful to prevent the initiation of ELTs. A window of atrial rate acceleration detection (WARAD) is initiated with the sensing of every sinus event and equals 75% of the preceding PP interval. If an atrial event is sensed during this period, as are premature atrial contractions (PACs), no atrioventricular (AV) delay is initiated, but an atrial pulse output is delivered and a subsequent 31-msec AV delay is started. Theoretically retrograde P waves are premature compared to sinus rhythm. They are therefore detected as PACs, and do not initiate AV delay, thus prohibiting the induction of ELTs. This function was tested in six patients, using external or implanted Chorus 2 pacemakers. Short PVARP (203 msec) and high atrial sensibility were programmed. Retrograde conduction was induced either by inefficient atrial pacing or a long programmed AV delay. Two different dual chamber settings were tested: dual chamber pacing with the fallback function On or Off. In every situation, the function proved effective in preventing ELTs: the number of tachycardia episodes went from 124 with the function programmed Off to 5 with the function programmed On for comparable durations. More than 75 ELTs effectively prevented by fallback have been recorded. PMID- 1437666 TI - Traveling medicine shows: a modern update? PMID- 1437667 TI - Acute renal failure in bone marrow transplantation. AB - Acute renal failure (ARF) is a serious complication in clients who have undergone bone marrow transplantation (BMT). The majority of cases develop as a result of intrarenal damage. Renal ischemia or nephrotoxic drugs, free hemoglobin, and free myoglobin contribute to acute tubular necrosis (ATN), which is the most likely cause of ARF in BMT clients. Nursing care of hospitalized BMT clients is directed toward the prevention of ARF by identifying clients who are at risk, the early diagnosis of renal impairment, and the administration of comprehensive treatment. Nurses play a vital role in the early diagnosis of renal impairment by assessing the client's fluid status, serum and urine electrolyte levels, and daily weights. The nursing role in managing clients with ARF includes preventing drug nephrotoxicity, maintaining fluid and electrolyte balance, preventing infection, and providing emotional support. PMID- 1437668 TI - Management of neutropenic enterocolitis in the patient with cancer. AB - Neutropenic enterocolitis is a life-threatening condition often seen in patients experiencing prolonged periods of neutropenia from conditions such as leukemia and lymphoma and from aggressive chemotherapy regimens. Its exact pathologic process remains unclear; however, it has been proposed that direct cytotoxic damage occurs to the bowel mucosa with subsequent microbial invasion complicated by the lack of adequate neutrophil response. The damage may progress to bowel perforation and septic shock. Early recognition and management by healthcare team members are crucial for the improved prognosis of these individuals. Controversy continues to exist concerning management options and the timing of these interventions. This article outlines nursing and medical management of the patient with neutropenic enterocolitis. PMID- 1437669 TI - Unconventional cancer treatments: professional, legal, and ethical issues. AB - A significant number of patients with cancer use or seriously consider using unconventional treatments. When patients or their families seek or use unproven treatment methods, the oncology nurse may face complex professional, legal, and ethical issues. This article addresses the possible reasons why patients and families may choose unconventional treatments. Oncology nurses are challenged to become aware of their many and varied nursing responsibilities. These responsibilities are examined in light of applicable codes and nursing practice standards, the clinical situation, and the values that are unique to each patient and family. Guidelines are offered for the oncology nurse to assist patients and families in choosing among treatment options. PMID- 1437670 TI - Diagnosis, treatment, and nursing management of the patient with hemochromatosis. AB - Hemochromatosis results when the body's iron stores progressively increase. Surplus iron stored in body tissues leads to organ dysfunction and death. Warnings that elevated iron stores increase the risk of cancer development necessitate a review of this condition. Two types of hemochromatosis, hereditary and secondary, are diagnosed in today's hematology-oncology practices. Distinguishing the differences with respect to etiology and management is essential to the risk assessment and long-term nursing management of this patient population. PMID- 1437671 TI - The relationship of visual acuity, tactile sensitivity, and mobility of the upper extremities to proficient breast self-examination in women 65 and older. AB - The purpose of this study was to describe the relationship of visual acuity, tactile sensitivity, and mobility of the upper extremities to the performance of proficient breast self-examination (BSE) in women 65 and older. A convenience sample of 32 women, ages 66-89, met with the investigator to have their visual acuity, tactile sensitivity, and upper extremity mobility tested. Their ability to perform the visual, tactile, and upper extremity components of proficient BSE also was tested by using simulated breast models (SBMs). Thirty of the women had adequate visual acuity (< or = 20/40 Snellen equivalent) but were unable to visually detect the abnormalities on the SBM. Thirty of the women had tactile sensitivity of 10 mm (1 cm) or better on the static two-point discrimination test of the second, third, and fourth digits of each hand. Yet, only 13 of these women were able to locate the 1 cm lump; only 12 were able to locate the 5 mm lumps; and none were able to locate the 3 mm lump. The subjects' ability to pass the upper extremity mobility component of proficient BSE was significantly related to their ability to pass the upper extremity range of motion criteria. Limitations and deficits, mostly of the hands and shoulders, were revealed. When teaching BSE to older women, nurses are responsible for assessing limitations and deficits in their ability to perform proficient BSE and, if necessary, for intervening with alternatives. The need for further research in this area is indicated to improve assessment and education of older women regarding the use of proficient BSE for early detection of breast cancer. PMID- 1437672 TI - Breast biopsy support program: collaboration between the oncology clinical nurse specialist and the ambulatory surgery nurse. AB - Nurses play a vital role in the care of women admitted to an ambulatory unit for a breast biopsy. This paper offers one aspect of a psychosocial model that the oncology clinical nurse specialist and the ambulatory surgery nurse can use collaboratively to meet each woman's needs during this critical period. Goal directed communications are the focus of this paper. Five specific techniques are described and can be used before biopsy reports are known, after women are informed that results are either negative or pending, and after reports are confirmed as positive. Psychosocial support is recognized as an important aspect of nursing care provided to women diagnosed with breast cancer. Although only 10% of women undergoing breast biopsies are diagnosed with malignant lesions, nurses must provide optimal support and guidance to every woman admitted for this surgical procedure. PMID- 1437673 TI - The development and testing of a nursing model of morbidity in patients with cancer. AB - Although oncology nurses are concerned about patient morbidity associated with cancer and its treatment, a comprehensive morbidity model from the perspective of nursing has yet to be developed. The purpose of this study was to begin to develop a morbidity model relevant to patients with cancer receiving treatment in the ambulatory care setting. The model was empirically tested with a sample of 100 patients with cancer beginning chemotherapy. Three domains emerged from the model: physiologic/pathophysiologic, functional, and psychological. Indices of morbidity within each domain were tested to establish beginning reliability and validity of the model. The results that were obtained indicate significant correlations among many of the indices within each domain (e.g., performance status, mood disturbance, patients' ratings of their current health); other indices did not contribute significantly to the model (e.g., type of cancer, history of recurrent disease, and patients' assessments of their health prior to developing cancer). Although further testing and refinement of the model is indicated, these preliminary findings reflect the model's potential for significant clinical relevance. By using this model, nurses could more readily profile patients at risk for increased morbidity and target their interventions accordingly. PMID- 1437674 TI - Gastrointestinal tract cancer: current knowledge, medical treatment, and nursing management. AB - Gastrointestinal (GI) cancer includes primary cancers of the esophagus, stomach, small intestine, large intestine, and rectum. This article presents an overview of the current knowledge, medical treatment, and nursing management for each of the identified sites, with a focus on surgical interventions and subsequent nursing care. Acute and long-term postoperative sequelae are addressed in addition to current state-of-the-art chemotherapeutic and radiation treatment modalities. This compilation of information regarding GI malignancies is useful for nursing as a current reference as well as for specific patient care issues. PMID- 1437675 TI - Assessing master's programs in oncology nursing. PMID- 1437676 TI - Process implemented for using nursing research in practice. PMID- 1437677 TI - Cryotherapy used to reduce stomatitis. PMID- 1437678 TI - Standards being developed for assessing and managing stomatitis. PMID- 1437679 TI - Checking vital signs unnecessary with IVIG administration. PMID- 1437680 TI - Dentin permeability: sealing the dentin in crown preparations. AB - Provisional restorations of full crown preparations may permit more microleakage of bacteria and their products than the final castings do. However, most investigations of the sealing qualities of cemented castings have reported that they too permit dye leakage. One approach to the problem is to seal the dentin with dentin bonding agents at the completion of the crown preparation. This study evaluated the ability of six different dentin bonding agents to seal the dentin of crown preparations of human teeth in vitro using two independent techniques. The first technique quantitated fluid filtration across dentin before and after treatment with dentin bonding agents at one hour, one day, one week, and one month and after thermocycling. The second method measured silver nitrate penetration of the thin veneers of dentin bonding agents into the dentin. Both methods correlated well with each other. The best seals were obtained with Prisma Universal Bond 2 or Superbond powder plus liquid. The worst seals were found using Gluma and Superbond liquid only. Clearfil PhotoBond, Amalgambond, and Scotchbond 2 gave intermediate results. Although the dentin bonding agents tend to accumulate on chamfers, thereby increasing their thickness to 200-300 microns, the method looks promising as a simple way to protect the pulp from the consequences of microleakage. PMID- 1437681 TI - Explorer sharpness as related to margin evaluations. AB - Nine experienced operative dentistry faculty each used six different explorers of varying degrees of sharpness ranging from new to well-used to evaluate marginal acceptability on a device used to simulate gradations of vertical opening. In this study, the standard for the sharpest explorer point was determined to be 68 microns in diameter measured 40 microns from the tip. There was a positive correlation between the diameter of the explorer tip at 40 microns and the mean amount of opening that could be detected until the margin was declared unacceptable. Increased explorer dullness significantly handicapped even experienced graders when the explorer alone was used to evaluate visually inaccessible margins. PMID- 1437682 TI - Leakage patterns associated with glass-ionomer-based resin restorations. AB - This study compared microleakage patterns for glass-ionomer-cement-based resin systems with and without a separating agent placed between the glass ionomer and resin. Results indicated significant leakage (100%) at the dentin glass-ionomer interface for specimens without a separating agent. Those with a separating agent showed almost no leakage between the dentin and glass ionomer (10%) and some leakage at the resin/glass ionomer interface (40%). These results suggest that the forces of polymerization shrinkage are stronger than the chemical bond between glass-ionomer cement and dentin. This bond fails during resin polymerization, eliminating any supplementary retention gained through chemical adhesion to dentin and opening a pathway for microleakage. PMID- 1437683 TI - Rubber dam with washed field evacuation: a new approach. PMID- 1437684 TI - Retention grooves for the Class 2 amalgam restoration: necessity or hazard? PMID- 1437685 TI - In vitro marginal leakage of cervical composite restorations lined with a light cured glass ionomer. AB - The purpose of this research effort was to investigate the microleakage of cervical restorations lined with a light-cured glass-ionomer liner. Wedge-shaped cervical cavities were cut on extracted teeth with the gingival cavosurface margin involving dentin. The cavities were randomly assigned to each of each of three groups: (1) restored with a microfilled composite resin, (2) restored with a light-cured glass-ionomer liner and microfilled resin as in the "sandwich" technique, and (3) restored entirely with the light-cured glass-ionomer liner. Half of the specimens in each group were thermocycled. Microleakage of these restorations was assessed by dye penetration. The results showed that differences were more pronounced at the gingival margin. Composite restorations inserted over the glass-ionomer liner demonstrated significantly less leakage than when the liner was not used. PMID- 1437686 TI - The effect of multiple layers of die-spacer on crown retention. AB - The application of die-spacer to crown preparation dies prior to the fabrication of the cast crown is an acceptable procedure to improve the fit of the restoration. Previous studies have shown that the retention of the restoration will be improved, unchanged, or reduced when an appropriate thickness of die spacer is used. No studies have determined the effect on retention if excessive die-spacer is used. This study evaluated the effect of increasing die-spacer thickness on the retention of cast full crowns. Cast copings were fabricated on dies coated with either 0, 4, 8, 12, or 16 coats of die-spacer, cemented on the respective teeth, and removed using an Instron Universal Testing Machine. There were no statistically significant differences (P < or = 0.05) between the mean force required to remove the cemented copings. It appears that increasing the application of die-spacer up to 16 coats (151 micrometers) does not adversely affect the retention of cemented cast copings. PMID- 1437687 TI - Effect of grooves on resistance form of conservative Class 2 amalgams. AB - This study evaluated several means of providing retention for the approximal box in very conservative class 2 preparations (occlusal isthmus width 0.7 mm). Sixty class 2 mesio-occlusal cavities were prepared in sound human maxillary premolar teeth. Four types of retention grooves, 0.3-0.5 mm deep, were prepared at the axiofacial and axiolingual line angles and/or occlusal to those line angles. Specimens were loaded at an angle of 13.5 degrees from vertical in an Instron Universal Testing Machine until the restoration failed. Results indicate that grooves located occlusal to the axiopulpal line angle provided more resistance than conventional grooves (gingival to the axiopulpal line angle) or no grooves. The use of a short retention groove or retention point located occlusal to the axiopulpal line angle, but not extending to the occlusal cavosurface margin, provided greater retention while removing minimal tooth structure. PMID- 1437688 TI - Effect of coating materials on restorative glass-ionomer cement surface. AB - Historically glass-ionomer samples have been coated with a varnish to protect the material from the effect of water on the surface. However, varnishes have been shown to peel from this surface. The set cement matrix may become chalky and can erode rapidly. Light-cured glazing agents may demonstrate the ability to limit water movement across the setting-cement surface. In this in vitro study samples were investigated colorimetrically to evaluate the effect of water contamination. Perceivable differences were not found, particularly when a coating of light cured bonding or glazing agents was applied. We conclude that the color stability of glass-ionomer cements is enhanced with the use of a protective coating of light-cured bonding or glazing agents. PMID- 1437689 TI - Microleakage of Class 2 glass-ionomer-silver restorations in primary molars. AB - The aims of this study were to assess microleakage at the cervical margins of class 2 "sandwich" restorations placed with two glass-ionomer-silver cements in primary molars, to compare the quality of the occlusal margins of these restorations to those prepared with Miracle Mix and Ketac Silver, and to assess by scanning electron microscopy (SEM) the marginal micromorphology of those restorations. Fifty-two class 2 restorations were prepared in extracted primary molars and were restored as follows: 1) Ketac Silver + Estilux Posterior (sandwich), 2) Miracle Mix + Estilux Posterior (sandwich), 3) Ketac Silver only, and 4) Miracle Mix only. No or minimal leakage was evident in most of the occlusal margins, whereas severe leakage was observed in almost 70% of the cervical margins of the Ketac Silver groups. Scanning electron microscopy evaluation demonstrated good adaptation at the buccal and lingual margins of all the restorations. Sixty-seven percent of the Miracle Mix restorations had no defects at the cervical margins, as opposed to only 17% of those with Ketac Silver. PMID- 1437690 TI - Placement and replacement of amalgam restorations in Italy. AB - The reasons for placement and replacement and the longevity of amalgam restorations were recorded by 62 Italian private practitioners. The survey compiled 1935 amalgam restorations inserted due to primary caries (59%) and failed restorations (41%). The clinical diagnosis of secondary caries constituted 59% of failures of amalgam restorations. The age of 46% of the restorations needing replacement was noted. The median longevity was 4.7 years. PMID- 1437691 TI - Enhanced prosthetics using the gingival mask. AB - The removal and trimming of working model dies destroys important soft tissue information. Features such as the gingival sulcus, interdental papilla, and ridge form are often destroyed. The loss of these features makes the fabrication of correct restoration contours difficult. Using the gingival mask will restore vital soft tissue as well as hard tissue information. This paper discusses the gingival mask, its advantages and disadvantages, and describes the direct and indirect methods of fabrication. Whatever method is employed, the gingival mask will prove to be a valuable adjunct for improving the quality and esthetic values of the fixed prosthesis. PMID- 1437692 TI - Permeability of root dentin to epinephrine released from gingival retraction cord. AB - The permeation of racemic epinephrine across roots of human molar crown segments was studied in vitro. Permeation was measured in the presence of cementum, with cementum removed (dentin exposed), and with and without dentin smear layers. Epinephrine was initially detected at 10 minutes and reached a steady state in 70 minutes. Epinephrine flux (the product of concentration and the flow rate per unit of dentin surface area) significantly increased when both the cementum and dentin smear layers were removed. The T1/2 (half-time in minutes necessary to reach steady-state diffusion) was zero with intact cementum and increased to approximately 40 minutes in dentin with and without smear layers. This study suggests that the permeation of epinephrine across root surfaces is prevented by the presence of cementum and retarded by the presence of dentin smear layers. Also, the data suggest that root dentin is another source of absorption when epinephrine-impregnated retraction cord is applied to the gingival sulcus. PMID- 1437693 TI - In vitro evaluation of the use of resin liners to reduce microleakage and improve retention of amalgam restorations. AB - This in vitro study evaluated the ability of three commercially available adhesive resins to reduce microleakage and provide retention between amalgam restorations and tooth structure. Results indicated that Amalgambond reduced leakage significantly more than Panavia EX, Prisma Universal Bond 2, and Copalite. In addition Amalgambond and Panavia EX exhibited the ability to bond amalgam to tooth structure. These results suggest that Amalgambond has the potential for serving successfully as a cavity liner with amalgam. PMID- 1437694 TI - Independent practice for hygienists and laboratory technicians. PMID- 1437695 TI - Placement and replacement of resin-based composite restorations in Italy. AB - The use of resin-based composite restorations, the reasons for failure, and the longevity of these restorations have been surveyed in 62 Italian private practices. Almost two-thirds of the 1025 restorations inserted were class 3 and 5 restorations, while 18% were class 1 and 2 restorations. Secondary caries was the most common reason reported for replacement of resin-based composite restorations (44%), followed by discoloration (21%), and bulk and margin fracture (14%). The age of restorations needing replacement was reported for 53% of the sample. The median longevity in this sample was calculated to be 3.3 years. PMID- 1437696 TI - Stress analysis of five prefabricated endodontic dowel designs: a photoelastic study. AB - The stress generated by five prefabricated endodontic dowel designs was evaluated using a two-dimensional photoelastic model. Cemented posts caused the least stress. Of the threaded posts, Flexi-post and Radix Anker produced the least stress; Kurer Crown Anchor produced the most. PMID- 1437697 TI - Regional variation in permeability of young dentin. AB - Variation in the permeability of dentin in people 19 years and less in age was evaluated. The regions compared were the occlusal third versus the middle third versus the cervical third of approximal surfaces. Also compared were the mesial approximal surface versus the distal. The comparison was done by obtaining 1 mm thick dentin discs from the area of dentin close to the dentinoenamel junction. It was seen that the cervical area was significantly more permeable than the occlusal area. The middle third, though not statistically significant, had mean values almost twice those in the occlusal third and almost half of the values in the cervical third. No difference was seen in permeability between the mesial and distal surfaces. The reasons for these regional variations and their clinical implications are presented. PMID- 1437698 TI - Drug development and women: an overview. PMID- 1437699 TI - Pharmacokinetics of low-dose methotrexate in adult asthmatics. AB - Several reports have been published on the disposition of methotrexate (MTX) when given in low dosages, but none in asthmatic patients. To address this matter, pharmacokinetic studies were performed in nine patients with severe, steroid requiring asthma (ages 18-76 yrs) after the sixth weekly intramuscular dose of MTX. Theophylline pharmacokinetic studies were also performed at baseline prior to the start of MTX treatment and at the time of the MTX studies. Total systemic clearance of MTX, given as mean (SD), was 122.6 (25.1) ml/minute, volume of distribution at steady state 0.49 (0.2) L/kg, half-life 3.1 (0.3) hours, mean residence time 5.0 (0.6) hours, and renal clearance 89.1 (36.3) ml/minute. These values are similar to those previously reported for other patient populations receiving low-dose MTX. Eight of these patients were evaluated for changes in theophylline pharmacokinetics. Theophylline clearance at week 6 decreased an average of 19% from baseline and correlated inversely with total MTX clearance. Percentage change in theophylline clearance from baseline was inversely correlated with MTX nonrenal clearance, but was not statistically significant. This finding may indicate competition for clearance pathways between MTX and theophylline. PMID- 1437700 TI - Bacterial resistance to beta-lactams, and its prevention with combination antimicrobial therapy. AB - The clinical and economic impacts of bacterial resistance are substantial. The development of bacterial resistance during a course of therapy often leads to clinical failure, prolonged hospitalization, increased morbidity, mortality, and increased health care costs. Resistance has been reported to occur most frequently with aminoglycosides, quinolones, and beta-lactam antimicrobials, and often occurs during the course of treatment of gram-negative bacillary infection. Resistance is most commonly due to enzymatic inactivation, permeability changes, or receptor mutation. Strategies for the prevention of resistance include appropriate infection-control practices, judicious use of antimicrobials, enhancement of host defenses, and the use of antimicrobial combinations. Despite success in vitro and in experimental animal models of infection, clinical trials in humans of antimicrobial combinations for the prevention of resistance have yielded mixed results. Use of the most potent agents available, preferably in bactericidal synergistic combinations, may be effective in preventing in vivo emergence of bacterial resistance. PMID- 1437701 TI - Nonprescription ibuprofen: side effect profile. AB - Single doses of nonprescription analgesics are commonly used to treat self diagnosed conditions. To evaluate the safety of single doses of nonprescription strength ibuprofen, we examined reported side effects from 15 double-blind, randomized, controlled trials we conducted of the drug to treat various common painful conditions (e.g., headache, sore throat). All studies included placebo and another nonprescription analgesic, acetaminophen. A total of 878 subjects received ibuprofen 200 or 400 mg, 849 acetaminophen 650 or 1000 mg, and 852 placebo. The overall frequency of side effects was comparable: ibuprofen 2.4%, acetaminophen 3.2%, and placebo 2.1%. The frequency of central nervous system symptoms was 0.8%, 2.1%, and 0.9%, respectively. Upper gastro-intestinal upset ranged from 0.8-0.9% of subjects in all groups. We conclude that single doses of nonprescription ibuprofen are well tolerated and demonstrate a side effect profile indistinguishable from that of acetaminophen and placebo. PMID- 1437702 TI - Exacerbation of congestive heart failure secondary to moricizine. AB - Moricizine, a recently approved phenothiazine antiarrhythmic agent, is reported to be associated with a low frequency of congestive heart failure. A 61-year-old man with a history of congestive heart failure and ischemic heart disease began taking moricizine 250 mg every 8 hours to suppress his monomorphic sustained ventricular tachycardia. After five doses he became progressively short of breath and was in pulmonary edema. Moricizine was discontinued, intravenous diuretics were administered, and the patient's clinical status stabilized. Twelve hours later, however, he developed polymorphic ventricular tachycardia and was not successfully resuscitated. Despite claims as to its safety, limited data strongly suggest that moricizine, like other antiarrhythmics, may be detrimental in patients with preexisting ventricular dysfunction, and should be prescribed with caution. PMID- 1437703 TI - Theophylline-mexiletine interaction: a case report. AB - Theophylline and mexiletine can be prescribed in patients with chronic obstructive pulmonary disease with coexistent arrhythmias. The drugs have common metabolic pathways that may result in an interaction. A patient who was taking theophylline became toxic after the initiation of mexiletine. Discontinuation of mexiletine led to an improvement in theophylline clearance. PMID- 1437704 TI - Pharmaceutical education. A commentary from the American College of Clinical Pharmacy. PMID- 1437705 TI - Structural and functional characterization of neuropeptides involved in the control of male mating behavior of Lymnaea stagnalis. AB - Mating as a male in the simultaneous hermaphrodite freshwater snail, Lymnaea stagnalis, comprises a series of complex behaviors that are a prelude to copulation. Copulatory behavior itself is assumed to be controlled by various types of peptidergic neurons as well as serotonergic cells. Here we report the primary structure of two peptides that were extracted from a cluster of neurons that innervates the penial complex and that is located in the anterior lobe of the right cerebral ganglion. The sequences of the peptides were determined as: Ala-Pro-Gly-Trp-amide and Ser-Gly-Ser-Asp-Tyr-Cys-Glu-Thr-Leu-Lys-Glu-Val-Ala-Asp Glu-Tyr-Ile-Leu- Leu- Ser-Tyr-Lys-Ile-Glu-Glu-Gln-Arg-Ala-Ala-Asp-Cys-Gly-Gly-Glu Pro-Pro-Asn- Ser- Gln(amide), respectively. The longer peptide is a homodimer. Both peptides are processed from the recently identified Ala-Pro-Gly-Trp-amide prohormone, which is expressed in the neurons of the anterior lobe of the right cerebral ganglion. Ala-Pro-Gly-Trp-amide could also be recovered from the penial complex. This peptide, when applied in vitro, inhibits the contractions of the penis retractor muscles evoked by serotonin in a dose-dependent fashion. PMID- 1437707 TI - Immunohistochemical localization of delta sleep-inducing peptide (DSIP) in the brain and pituitary of the cartilaginous fish Scyliorhinus canicula. AB - The distribution of delta sleep-inducing peptide (DSIP) in the brain and pituitary of the cartilaginous fish Scyliorhinus canicula was investigated using the indirect immunofluorescence technique. Delta sleep-inducing peptide-like immunoreactive cell bodies were mainly observed in the nucleus lateralis tuberis of the hypothalamus. Immunolabeled perikarya were also distributed in the nucleus lobi lateralis hypothalami and in the dorso-lateral wall of the recessus posterioris. Most of these cells, located in the subependymal layers of the infundibulum and lateral lobes, had the typical aspect of cerebrospinal fluid contacting elements. The DSIP-like immunoreactive fibers were localized in the basal telencephalon, within the regions of the nucleus interstitialis commissurae anterioris and the nucleus entopeduncularis. A dense network of DSIP-positive fibers was seen throughout the midcaudal hypothalamus, the lateral lobes, and the posterior lobe. In the pituitary, numerous DSIP-like immunoreactive cells were detected in the median lobe of the pars distalis. In particular, a high concentration of cells was seen in the dorsal wall of the median lobe, an area which is known to contain melanin-concentrating hormone (MCH)-producing cells. Comparison of the distribution of DSIP- and MCH-like immunoreactive cells revealed that the two neuropeptides are stored in the same cells of the median lobe of the pituitary. These findings provide the first evidence for the presence of a DSIP-related peptide in fish. The distribution of the immunoreactive material supports the view that DSIP may act as a neuromodulator and/or a hypophysiotropic factor. Moreover, the presence of DSIP-like immunoreactive cells in the pars distalis suggests that this peptide may exert autocrine or paracrine effect in the pituitary. PMID- 1437706 TI - Isolation of peptides arising from the specific posttranslational processing of chromogranin A and chromogranin B from human pheochromocytoma tissue. AB - An extract of human adrenal medullary pheochromocytoma tissue was fractionated by gel permeation chromatography, and peptides of major abundance in the approximate molecular mass range 1000-4000 were purified to apparent homogeneity by reverse phase HPLC. Determination of the primary structures of four such peptides demonstrated that they were fragments of either chromogranin A or chromogranin B. The peptide WSKMDQLAKELTAE represents chromogranin A(324-337), the peptide LGELFNPYYDPLQWKSSHFE represents chromogranin B(498-517), the peptide NLARVPKLDL represents chromogranin B(568-577), and the peptide QYDRVAQLDQLLHY (isolated as the N-terminal pyroglutamyl derivative) represents chromogranin B(580-593). Analysis of the nucleotide sequences of cDNAs complementary to human chromogranin A and B messenger RNAs indicates that each of these peptide sequences is flanked by pairs or groups of basic residues, suggesting that these fragments are the products of specific posttranslational processing. In addition, a peptide identified as chromogranin B(496-517) was isolated from extract. This component represents the product of incomplete proteolytic cleavage at the Lys494-Arg495 Lys496-Arg497 processing site in chromogranin B. A minor component in the extract was identified as chromogranin B(508-517), but this component probably represents an artifact of the extraction procedure arising from the hydrolysis of the acid labile Asp507-Pro508 bond. The study has shown that chromogranin A and B in pheochromocytoma tissue function as the precursors of several small peptides that may have a regulatory role. PMID- 1437708 TI - Bombyxin-II and its disulfide bond isomers: synthesis and activity. AB - Bombyxin-II, an insulin superfamily peptide of the silkmoth Bombyx mori, and its disulfide bond isomers have been synthesized by two ways of stepwise, semi regioselective disulfide bond formation. The disulfide bond CysA20-CysB22 or CysA7-CysB10 was formed first, and then the two other disulfide bonds were formed by iodine oxidation. The conditions for the iodine oxidation were improved to suppress oxidative degradation of unprotected Trp residues. With these conditions, bombyxin-II was synthesized in high yields (26% and 32%). Its disulfide bond isomers were also obtained. Specific activity of the products indicates that the disulfide bond CysA20-CysB22 is important to the bombyxin activity. PMID- 1437709 TI - Fluorescent N-methylanthranilyl (Mantyl) tag for peptides: its application in subpicomole determination of kinins. AB - Highly fluorescent N-methylanthranilyl (Mantyl) peptide derivatives were prepared by a one-step reaction with N-methylisatoic anhydride (MIA) for quantitative detection in HPLC. Reactions were carried out in an organic medium of acetonitrile-triethylamine, in aqueous alkaline sodium carbonate and sodium phosphate buffers. 4-Dimethylaminopyridine (DMAP) catalyzed specific mantylation of -NH2 groups of peptides in the organic reaction medium. The DMAP had no effect in the aqueous buffered reaction systems. Proline amino-terminal peptides reacted equally well with MIA. Mantyl-bradykinin had excitation and fluorescence maxima at 350 nm and 426 nm in water and water/acetonitrile (ACN)/trifluoroacetic acid (TFA) solvent mixtures, respectively. Fluorescence intensity increased with an increase in ACN concentration and decreased with an increase in acid content. Mantyl kinins were completely resolved on a C18 reversed phase HPLC column using an ACN-0.1% TFA gradient and their behavior on the column was similar to having an extra amino acid. Di-Mantyl derivatives obtained with Lys-BK and Met-Lys-BK did not exhibit fluorescence appreciably higher than Mantyl-BK. Fluorescence detection of Mantyl kinins was about 50-100 times more sensitive (lower limits of 0.1 to 0.5 picomole) than UV detection of the phenylisothiocyanate-derivatized kinins under typical HPLC conditions. PMID- 1437710 TI - Insulin in the vitreous of the normal and streptozotocin-induced diabetic rat. AB - Insulin has been detected by ELISA in the vitreous of the normal and streptozotocin-diabetic rat at levels for both about 1% of those in serum. 131I labeled insulin, administered to conscious rats via an indwelling cannula in the right atrium, was found to cross the blood-ocular barrier into the vitreous. Autoradiographic gel analysis showed the peptide was transferred as an intact molecule. Vitreous insulin levels reflected serum levels as seen in relatively constant vitreous-to-serum insulin ratios over a wide range of serum insulin concentrations. The rate of blood-to-vitreous passage of insulin was about the same in normal as in diabetic rats (fasting serum glucose greater than or equal to 21 mM). At least a portion of vitreous insulin is therefore of pancreatic origin, and retinal tissue in the normal and diabetic animal is thus accessible to circulating hormone. The blood-ocular barrier is unaltered in streptozotocin diabetes with regard to insulin passage. PMID- 1437712 TI - Distribution and coexistence of urotensin I and urotensin II peptides in the cerebral ganglia of Aplysia californica. AB - Urotensin I (UI) and urotensin II (UII) were demonstrated in the cerebral ganglia of Aplysia californica by applying immunocytochemical and radioimmunoassay procedures. Sequential analysis of adjacent sections of the cerebral ganglia of Aplysia demonstrated that the UI-immunoreactive (UI-IR) neurons of the F cluster of the cerebral ganglia also contained UII immunoreactivity (UII-IR). Both UI-IR and UII-IR were also observed in a cuff-like arrangement of fibers surrounding the proximal portion of the supralabial nerve, as well as in a few fibers in the anterior tentacular nerves. The UI-IR perikarya of the cerebral ganglia appeared to project to the entire CNS of Aplysia, but the UII-IR fibers appeared only in the neuropile and commissure of the cerebral ganglia. The UI-IR staining was abolished by previous immunoabsorption of the UI antiserum with sucker (Catastomus commersoni) UI, but not with ovine corticotropin-releasing factor (CRF), rat/human CRF, or goby (Gillichthys mirabilis) UII. Immunostaining with UII antiserum was quenched by goby UII, but not by sucker UII-A, UII-B, UII-A(6 12), or carp (Cyprinus carpio) UII-alpha and UII-gamma. The UII staining was not abolished by UI or somatostatin. The F cluster was not stained when a somatostatin antiserum was applied. Radioimmunoassay of dilutions of cerebral ganglia extract, using UII antiserum, revealed a parallel displacement curve to synthetic goby UII.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437711 TI - Catabolism of rat growth hormone-releasing factor(1-29) amide in rat serum and liver. AB - Clinical and veterinary uses of growth hormone-releasing factor [GRF(1- 29)NH2] require the design of analogs that are resistant to proteolysis by serum and liver degrading enzymes. This study investigated rat GRF(1-29)NH2 processing in serum and liver homogenate by means of high pressure liquid chromatography (HPLC). Synthetic rGRF(1-29)NH2 (30 microM) was incubated (0-120 min, 37 degrees C) in serum (49 +/- 8 mg prot./ml). The rGRF(1-29)NH2 (10 microM) was also incubated (0-120 min, 37 degrees C) with liver homogenate (200 +/- 6 micrograms prot./ml). Time course studies of rGRF(1-29)NH2 disappearance showed apparent half-lives of 18 +/- 4 min and 13 +/- 3 min in serum and liver homogenate, respectively. This was accompanied by the appearance of degradation products that were all less hydrophobic than the native peptide. In the serum, two major metabolites were detected and isolated by preparative HPLC. Combined results of amino acid analysis, sequencing, and chromatography with synthetic homologs revealed the presence of rGRF(1-20)OH and (3-20)OH. A small amount of rGRF(12 29)NH2, coeluting with rGRF(3-20)OH, was also found by sequencing. In the liver, rGRF(1-18)OH, (3-18)OH, and (1-10)OH were identified. The peptide bond Ala2-Asp3 (DPP IV cleavage site) was hydrolyzed in both serum and liver. Other tissue specific cleavage sites were Arg11-Arg12 and Arg20-Lys21 (trypsin-like cleavage site) in the serum, and Tyr10-Arg11 and Tyr18-Ala19 (chymotrypsin-like cleavage site) in the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437713 TI - A comparison of the effects of mesencephalic injections of neurotensin(1-13) and neuromedin N on brain electrical self-stimulation. AB - Neuromedin N (NM-N), a hexapeptide that shares a four amino acid C-terminal homology with the tridecapeptide, neurotensin (NT), has been suggested as a potential neurotransmitter or neuromodulator that could interact with the NT sensitive receptors. In this experiment, we compared the effects of an equimolar concentration of NM-N and NT(1-13) injected in the ventral tegmental area (VTA) on brain electrical self-stimulation (SS), a behavior previously shown to be potentiated by VTA injections of NT(1-13). Rats implanted with a stimulating electrode in the mesencephalic central gray and a guide cannula in the VTA were trained to lever press to obtain rewarding electrical stimulations. Functions relating the rate of lever pressing to the stimulation frequency were determined, on separate daily tests, before and after the injection of 3 nmol of NM-N, NT(1 13), or an equal volume of saline vehicle. At this concentration, both NM-N and NT(1-13) produced a significant facilitation of SS when compared to saline vehicle, an effect that was not seen when the peptides were injected outside the VTA. The facilitation of SS by NM-N, however, was much weaker and of a shorter duration than the one produced by NT(1-13). The shorter time course and the weaker behavioral effect of NM-N compared to NT(1-13) are consistent with its lower potency at the NT receptor and its faster rate of enzymatic degradation in the VTA, and suggest that NM-N potentiated the reward-relevant neural signal by acting on mesencephalic NT receptors. PMID- 1437714 TI - Insulin deficiency is a specific stimulus to hypothalamic neuropeptide Y: a comparison of the effects of insulin replacement and food restriction in streptozocin-diabetic rats. AB - Untreated insulin-deficient diabetes causes hyperphagia and neuroendocrine disturbances that may be partly mediated by increased hypothalamic activity of neuropeptide Y (NPY), a potent central appetite stimulant. The metabolic signal that stimulates hypothalamic NPY is unknown. This study aimed to determine whether insulin deficiency or hyperglycemia was responsible. Regional hypothalamic NPY concentrations were compared in streptozocin-diabetic (STZ-D) rats rendered nearly normoglycemic by either insulin replacement or food restriction. Untreated STZ-D rats were hyperphagic and showed significantly increased (p less than 0.01) hypothalamic NPY concentrations in the arcuate nucleus and lateral hypothalamic area. Once-daily ultralente insulin injections corrected hypoinsulinemia and hyperglycemia, abolished hyperphagia, and normalized NPY concentrations in all hypothalamic regions. By contrast, food restriction effectively lowered glycemia without raising insulin levels. In these underfed diabetic rats, NPY concentrations rose further and were significantly higher than nondiabetic and untreated diabetic levels in most hypothalamic regions. We conclude that insulin deficiency is a major stimulus to hypothalamic NPY in STZ-D, whereas hyperglycemia may exert an inhibitory influence. These findings support the hypothesis that hypothalamic NPY responds to specific metabolic cues and is involved in regulating energy balance and conserving body weight. PMID- 1437715 TI - Endorphins do not affect behavioral stress responses in mice. AB - Effects of endorphins on behavioral stress responses were investigated in mice. For this purpose, we used environment-induced conditioned suppression of motility and forced swimming-induced immobility. The cerebral ventricular administration of alpha-endorphin (2.5-10 nmol), beta-endorphin (0.38-1.5 nmol), or gamma endorphin (2.5-10 nmol) failed to affect either the environment-induced conditioned suppression of motility or the forced swimming-induced immobility. We have indicated previously that enkephalins attenuate both stress responses and, in contrast, dynorphin potentiates them. These findings indicate that the endorphinergic systems are not responsible for behavioral stress responses and that the role played by endorphins in the present stressful situations may be different from that of enkephalin and dynorphin. PMID- 1437716 TI - Expression of angiotensin II AT2 receptors in the rat skin during experimental wound healing. AB - We localized and characterized angiotensin II AT1 and AT2 receptors in the skin of 2-week-old rats during experimental wound healing. Both AT1 and AT2 were present in the skin. Three days after wounding, the expression of angiotensin II receptors was significantly enhanced in the dermis as well as in a localized band within the superficial dermis of the skin surrounding the wound. The major proportion of this increase was due to angiotensin II AT2 receptors. Our results suggest a physiological role for AT2 receptors in the process of tissue repair. PMID- 1437717 TI - Synthesis and biological activity of novel C-terminal-extended and biotinylated growth hormone-releasing factor (GRF) analogs. AB - A series of novel hGRF(1-29)-NH2 analogs were synthesized and biotinylated. The immunological and biological activities of these analogs were then characterized. To distance the biotin moiety from the putative bioactive core, a C-terminal spacer arm consisting of -Gly-Gly-Cys-NH2 (-GGC) was added to hGRF(1-29)-NH2 (hGRF29) and analogs, with subsequent biotinylation performed at the cysteine residue. Neither addition of the C-terminal spacer arm nor biotinylation affected affinity of these analogs for GRF antibody. Relative to hGRF(1-44)-NH2 (hGRF44: potency = 1.0), the biotinylated analogs were equipotent in vitro to their nonbiotinylated, parent compounds: [desNH2Tyr1,D-Ala2,Ala15]hGRF29-GGC-(tpBiocyt in)-NH2 (4.7) = [Ala15]hGRF29-GGC-(tpBiocytin)-NH2 (3.9) greater than hGRF29-GGC (tpBiocytin)-NH2 (0.8). Based upon cumulative GH release data in vivo (0-60 min postinjection), [desNH2Tyr1,D-Ala2,Ala15]hGRF29-GGC-(tpBiocyt in)-NH2, [Ala15]hGRF29-GGC-(tpBiocytin)-NH2, and hGRF29-GGC-(tpBiocytin)-NH2 displayed 8.6, 5.5, and 0.8 times, respectively, the potency of hGRF44. These in vivo potency values were not significantly different from the corresponding parent compounds (i.e., with or without the C-terminal spacer arm). In summary, biotinylated hGRF analogs have been developed that retain full immunoreactivity and potent bioactivity (in vitro and in vivo), thus permitting their use in GRF receptor isolation, ELISA, and histochemical procedures. PMID- 1437718 TI - Role of tyrosine kinases in bombesin regulation of gastric mucosal proliferative activity in young and aged rats. AB - In vivo and in vitro experiments were performed to examine the responsiveness of the gastric mucosa to the growth-promoting action of bombesin in young (4 months) and aged (22 months) Fischer 344 rats. In addition, the role of tyrosine kinase (Tyr-K) in regulating this action of bombesin was also examined. In young rats, infusion of bombesin (300 ng/kg/h) by osmotic minipump for 2 weeks resulted in a significant 100% increase in mucosal DNA synthesis and ornithine decarboxylase (ODC) activity. These increases were accompanied by a 32% (p less than 0.025) rise in gastric mucosal overall Tyr-K activity and a 71% (p less than 0.001) increase in Tyr-k activity associated with pp60c-src, when compared with the corresponding controls. The bombesin-induced stimulation of pp60c-src Tyr-k activity was also associated with a 25% increase in phosphorylation of this protein. In contrast, in aged rats, none of these parameters were affected by bombesin. A similar phenomenon was also observed when mucosal explants from young and aged rats were exposed to bombesin in an organ culture system. Exposure of gastric mucosal explants from young, but not from aged, rats to 10(-8) M bombesin for 8 h resulted in a 300% (p less than 0.001) increase in ODC activity, a 150% (p less than 0.001) rise in Tyr-k activity, and a marked increase (400-600%) in tyrosine-specific phosphorylation of three membrane proteins with M(r) of 55, 44, and 41 kDa, when compared with the corresponding controls. However, these increases were totally abolished by genistein, a specific irreversible inhibitor of Tyr-k.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437720 TI - Localization of neurokinin B in the central nervous system of the rat. AB - The distribution of neurokinin B (NKB) was determined by immunocytochemistry with antisera directed toward its amino terminus. Immunoreactive perikarya were detected in the main and accessory olfactory bulbs, cortical regions, the olfactory tubercle, the bed nucleus of the stria terminalis, the diagonal band of Broca, the nucleus accumbens, the septum, the neostriatum, several hypothalamic nuclei, the superior colliculus, the central gray, the substantia nigra, the medullary reticular formation, and the external cuneate nucleus. The distribution of NKB-containing perikarya revealed by immunocytochemistry was similar to the distribution of protachykinin B-containing cells previously visualized by in situ hybridization. Immunoreactive nerve fibers and terminals were detected in all major subdivisions of the brain. The levels of NKB measured by radioimmunoassay were highest in the hypothalamus. The distribution of NKB in the rat brain was similar to the distribution of substance P; however, there were several regions where the two distributions were clearly different. PMID- 1437719 TI - Neuropeptide Y, peptide YY, and pancreatic polypeptide modulate duodenal and colonic motility at a thoracic spinal site in rats. AB - Neuropeptide Y, PYY, and PP (200 pmol) alter intraluminal pressure in the duodenum and colon of rats following their administration into the thoracic (T8 T10) region of the spinal cord. Neuropeptide Y decreases the tone of the duodenum and the colon following intrathecal (T8-T10) administration prior to an increase in tone to baseline or greater. There is no effect on intraluminal pressure of either the duodenum or the colon following intrathecal administration of NPY or PP into the lumbar (L4-L5) region of the spinal cord. Following intrathecal (T8 T10) administration of PYY and PP, increases in intraduodenal pressures are observed (+2.1 and +3.0 mmHg from saline baseline). Phasic contractions of the duodenum are increased following intrathecal administration of PYY into the thoracic spinal cord of rats. Neuropeptide Y, PYY, and PP increase intracolonic pressure +2.2, +3.3, and +3.7 mmHg from saline baseline, respectively. Phasic contractions of the colon are increased following PP intrathecal thoracic administration. Responsiveness of the duodenum or colon to the different ligands of the PP-fold peptide family in the absence of alpha-adrenergic blockade did not vary. The increases in intraluminal pressure of the duodenum and colon following intrathecal administration of the PP-fold peptides are attenuated by both alpha-1 adrenergic (prazosin) and alpha-2 adrenergic (yohimbine) blockade. There is a difference in responsiveness of the colon between the ligands of the PP-fold family in the presence of the alpha-2 adrenergic blockade. The findings of this study indicate that duodenal and colonic motility are modulated by the PP-fold peptides at thoracic spinal sites via alteration of sympathetic outflow. PMID- 1437721 TI - Behavioral responses elicited by intraperitoneal neurotensin in guinea pigs. AB - The potential behavioral responses to single intraperitoneal (IP) injection of neurotensin (NT) were examined in conscious, freely moving guinea pigs. Most animals injected with NT solvent (i.e., controls) or NT solution with low NT concentration (i.e., 5.4 nM) exhibited little or no particular behavioral reaction. On the other hand, 50 to 75% of the animals given IP injection of NT with 54, 540, or 5400 nM of NT exhibited motor responses characterized by a transient episode of clonic body jerks. Vocalization responses were observed in less than 25% of the animals given IP NT. Animal pretreatment with morphine reduced the incidence of motor and vocalization responses. The results were interpreted as an indication that IP injection of moderately concentrated NT solution (i.e., greater than or equal to 54 nM) is probably a weak noxious stimulus in conscious guinea pigs. PMID- 1437722 TI - [Infection with hepatitis delta virus among drug addicts]. PMID- 1437723 TI - [Hepatitis B among drug addicts]. AB - In the years 1980-1988 twenty five drug addicts were identified among 1841 patients hospitalized for acute hepatitis in the Dep. of Hepatology at the Institute of Infectious and Parasitic Diseases in Warsaw. 15 drug addicts had hepatitis B and 10 had hepatitis A. It was found, that the course of acute type B hepatitis was milder in drug addicts, than among control group consisting of non addicts. PMID- 1437724 TI - [Epidemic focus of non-A, non-B viral hepatitis in a plasmapheresis unit]. AB - Non-A, non-B hepatitis has been diagnosed in 12 blood donors in a plasmapheresis unit. The course of the disease has been symptomatic, accompanied by jaundice, fatigue, and nausea in 8 cases, and subclinical in the remaining 4 patients. Nine patients were followed-up to 2 years and only 2 patients liver biochemical tests were normalized permanently. The biopsies performed, a year after the acute phase of hepatitis period revealed chronic active disease in patients, chronic persistent hepatitis in 2 patients, acute hepatitis in one, and normal liver in one patient. Repeated liver biopsies, performed one year later, have basically shown similar lesions except one patient in whom chronic active hepatitis progressed to incipient liver cirrhosis. No symptoms of the disease have been usually noted in patients with chronic form of the disease, and liver function tests have occasionally been normal. PMID- 1437725 TI - [Plasmapheresis in the treatment of hepatic coma]. AB - Fourteen patients, including 6 with viral hepatitis B and 8 with liver cirrhosis were treated with plasmapheresis for hepatic coma. Altogether 29 plasmaphereses were carried out. Complete recovery was achieved in one patient with viral hepatitis B and in 3 patients with liver cirrhosis. Plasmapheresis should be performed in patients with severe lesions to the liver. Classification of patients to the treatment should include clinical examination, biochemical and enzymatic tests, and evaluation of liver reserve with isotope hepatography. In case of the acute poisoning with hepatotoxic agents indications to plasmapheresis should be evaluated from the toxicologic point of view. PMID- 1437726 TI - [Plasmapheresis in the treatment of hepatic coma complicating viral hepatitis]. AB - Therapeutic plasmaphereses using CS 3000 Fenwal Cell Separator were performed in 4 women and 2 men, aged between 17 and 44 years, with hepatic coma complicating acute viral hepatitis type B. One to four plasma exchanges per patient were performed, usually at the volume of 3000 ml per procedure. Two patients at II and IVa period of the coma, according to Aboun classification, survived. Four patients at II, III and two at III/IV period of the coma died. The authors suggest that in some cases exchange of large volumes of plasma in the treatment of hepatic coma complicating acute viral hepatitis may be a lifesaving procedure. PMID- 1437727 TI - [Use of the analysis of chromosomal changes in the prognosis of "fulminant hepatitis"]. PMID- 1437728 TI - [Phenazon metabolism in children with liver diseases]. PMID- 1437729 TI - [Evaluation of cellular and humoral immunity in men after occupational exposure]. AB - Hundred twenty seven adult men have been examined to determine an effect of the occupational exposure to lead on the immunity. A group of 77 men occupationally exposed to lead absorbed by respiratory has been selected on the basis of the determination of exposure to lead in their working places, detection of lead deposits and its metabolites in the body. Fifty men constituted a control group. They were exposed to lead corresponding to an exposure of general population. Immunological studies have shown that high lead levels in the occupational environment produced significant disorders in all stages of both types of immunological response--a decrease in the cellular and humoral immunity. PMID- 1437730 TI - [Multi-component preparations in present-day drug therapy]. PMID- 1437731 TI - [Hepatitis B virus infection in alcoholics]. AB - Chromosomal analysis has been carried out in 4 patients with the symptoms of hepatic coma. An analysis included lymphocytes cultured from peripheral blood. Chromosomal disorders have been assessed with two techniques: structural chromosomal aberrations test, and sister chromatid exchange (SCE) test. It has been shown that the extend of chromosomal damage in the form of the gaps, breaks, acentric chromosomes as well as the presence of ring and dicentric chromosomes, and micronuclear cells have been higher in the examined patients. Such changes may evidence DNA repair disorders, and the presence of micronuclear forms may seem an unfavourable prognosis. PMID- 1437732 TI - [Meta-analysis of the effectiveness of therapeutic methods]. PMID- 1437733 TI - [Problems of occupational poisoning with chemical substances and the functions of various endocrine and reproductive glands]. PMID- 1437734 TI - [Cerebral infarction--a general-medical problem]. AB - A knowledge of events accompanying the acute coronary failure may help understanding the acute cerebral blood flow insufficiency leading to brain infarction. Cerebral blood flow should be treated as an integral part of the systemic blood circulation. It is of importance when the disease produces lesions to the vascular wall, and the brain looses its autoregulation functions. In such a situation every extracerebral disorders--even slight--may produce extensive lesions to nervous tissue. Therefore, the treatment of the acute cerebral circulation failure requires proper functioning of all factors which may affect hemodynamics and tissue metabolism. Duration of cerebral flow disorders plays an important role in the avoidance of unfavourable complications such as brain infarction. Therefore, every physician is obliged to undertake any possible actions preventing such complications. PMID- 1437735 TI - [Brain stem insufficiency in acute ischemia and cerebral hemorrhage]. AB - Consciousness disorders are closely related to the general dysfunction of the brain stem, and called by some authors brain stem insufficiency. To evaluate the degree of brain stem dysfunction, an original scale has been elaborated. Each group of brain stem functions are scored. Consciousness being the most important symptom of the brain stem insufficiency is scored about 50% in a 63-score scale. Scores are used to achieve the most objectivity in the clinical monitoring of the brain stem insufficiency. Its utility was examined in 75 patients with either ischemia or cerebral hemorrhage. Patients of both groups with severe insufficiency below 33 scores and persisting over 24 hours had no chance to survive. The authors suggest that the scores may successfully be used in the clinical monitoring of all disorders producing consciousness disturbances. Survival of patients with brain stem insufficiency in the course of cerebral ischemia or hemorrhage depends on the degree and duration of the brain stem insufficiency. PMID- 1437737 TI - [The number and affinity of fibrinogen receptors in blood platelets of patients with ischemic stroke]. AB - Parameters of fibrinogen binding with blood platelets (number of receptors and their affinity) have been studied in patients with ischemic stroke. Due to the increased platelet ability to aggregate in the ischemic diseases such studies seem helpful. The studies involved 13 patients with ischemic stroke. Blood platelets collected from younger patients (under 50 years) possessed significantly higher number of receptors binding fibrinogen than blood platelets of healthy individuals (p less than 0.02). These receptors significantly more strongly bound ligand than those in the control group (p less than 0.05), and in the group of older patients with stroke (less than 0.05). Fibrinogen binding to blood platelets in patients over 50 years of age did not differ significantly from that in the control group. These results may indicate, that the increased platelet aggregation might be a significant pathogenic factor of the stroke in younger patients. PMID- 1437736 TI - [Physical activity in acute cerebrovascular insufficiency]. AB - It was noted that physical activity of 1052 patients hospitalized for the acute cerebral flow failure due to atheromatosis is an important indicator of the cerebral ischemia. Extension of ischemia evaluated on the basis of physical activity enables to foresee possible improvement and survival. Authors' own classification of physical activity may be helpful in the monitoring of cerebral flow failure therapy. PMID- 1437738 TI - [Rheological properties of blood in patients with ischemic stroke in selected clinical groups]. AB - Hemorheological parameters have been analysed in 34 patients with the acute ischemic stroke. The patients have been divided into two clinical subgroups: with accompanying arterial hypertension (group HA), and free of other diseases (group NHA). Comparative studies have not revealed the significant differences between both groups. However, blood viscosity has been significantly higher in the hypertensive patients. It was related to the decrease in the erythrocyte ability to elastic deformation Group NHA has been characterized by the high fibrinogen levels and by the decrease of the cerebral blood flow. PMID- 1437739 TI - [Calcitonin level in cerebrospinal fluid of patients with amyotrophic lateral sclerosis]. AB - Several data indicate that the dysfunction of some neuropeptide function may play a role in the pathogenesis of the amyotrophic lateral sclerosis. Therefore, the authors decide to determine a concentration of one of them in CSF, namely calcitonin. Calcitonin is widely distributed in CNS, including both anterior and posterior horns of the spinal cord. It was confirmed with immunohistochemical assays and an examination of the human CSF. Calcitonin concentration in CSF has been assayed in 12 patients with amyotrophic lateral sclerosis and in 12 patients of the control group. Calcitonin concentrations in CSF have been measured with RIA technique, using appropriate kits manufactured by Mallinckrodt Dgn. Mean calcitonin CSF concentration in patients with amyotrophic lateral sclerosis was 448. +/- 74.3 pg/ml, and was lowered in comparison with that in the control group, i.e. 613.9 +/- 147.2 pg/ml. The results confirm the authors' previous reports on the reduced content of some neuropeptides in CSF of patients with amyotrophic lateral sclerosis and suggest a possible calcitonin role in the pathogenesis of this disease. PMID- 1437740 TI - [Diagnosis of progressive open internal hydrocephalus in patients after cranio cerebral injuries and subarachnoid hemorrhage]. AB - Late internal hydrocephalus has been diagnosed in 68 (44%) out of 154 patients treated for the ruptured cerebral aneurysms, and in 37 (31%) out of 120 patients, who underwent cranio-cerebral trauma. To establish the indications for shunts, CT scans of the skull, tomoventriculography, and infusion tests have been carried out in 38 patients. It has been found, that increased transparency of the areas below cerebral ependyma, the lack of cerebral cortex sulci, and imaging of the temporal horns together with internal hydrocephalus in CT scans indicate an active process and are indications to shunting. If there are no signs of active process in CT scans despite of the presence of hydrocephalus, tomoventriculography should be performed to establish more fully the indications to shunting. PMID- 1437741 TI - [Relation between resorption resistance of cerebrospinal fluid and the degree of intracranial pressure]. AB - Changes in the CSF resorption resistance in relation to the value of the intracranial pressure have been assessed in 44 cats. Changes in the intracranial pressure have been produced with fluid infusions. Between 1 to 5 infusion tests with the rate 0.012-1.8 ml/min have been performed in each animal. A relationship between CSF resorption resistance and intracranial pressure has been found. With an increase in the intracranial pressure CSF resorption resistance increased to maximum value of 34 kPa/ml per minute (255.6 mm Hg/ml per minute) at pressure 2.96 +/- 0.69 kPa (22.2 +/- 5.2 mm Hg). At the intracranial pressure about 6.7 kPa (50 mm Hg) CSF resorption resistance rapidly decreased to the value of 13.9 kPa/ml per minute (104 mm Hg/ml per minute). Later, changes have been rather slight. It is possible, that the breaking point at 6.7 kPa corresponds to the mobilisation of all ways of CSF evacuation. PMID- 1437743 TI - [A new model of computerized encephalovolumeter for monitoring of acute cerebrovascular insufficiency]. AB - A new model of the computerized encephalovolumeter (EVM.IR) is presented. Infrared light is used as an information carrier enabling to follow the dynamics of intracerebral equilibrium and blood flow disorders. The authors suggest that this model would help clinical examination in the acute cerebral flow failure, and increase better evaluation of the efficiency of drugs improving cerebral blood flow. It should also help to foresee the outcome and prognosis. A new model of EVM.IR and its programs require further constructional and experimental studies before the routine use at ICUs. PMID- 1437742 TI - [Accidental fatal poisoning with ethyl fluoroacetate]. AB - Fluoroacetic salts belong to the most toxic chemicals. They are used for various purposes, and form stable compounds in some plants. A case of poisoning with ethyl fluoroacetate is presented in detail. Diagnostic problems and therapy which failed due to the late diagnosis and dramatic progress in the symptoms of poisoning are also discussed. Fluoroacetic ion alone is non-toxic but in vivo forms fluorotricarboxylic acid, which blocks cellular metabolism at the citrate stage. Symptoms occur with a delay but lethal synthesis of fluorotricarboxylic acid leads to the irreversible cellular dysfunction, especially in CNS and circulatory system. Poisoning may be treated with monoacetin and acetamide. An emphasis is on health hazards resulting from the exposure to fluoroacetate and necessity to observe strictly safety regulations. PMID- 1437744 TI - [Activities of the Stanislaw Konopka Main Medical Library]. PMID- 1437745 TI - [Extra-intracranial arterial anastomosis in the treatment of cerebral ischemia-- our present knowledge and conclusions for the future]. PMID- 1437746 TI - [Cost of the treatment of acute cerebrovascular insufficiency causing cerebral infarction]. AB - Many countries are interested in the cost of therapy of the acute cerebral flow insufficiency leading to brain infarction. Total costs include: drugs, laboratory tests, nursing care, the cost of patients' food, equipment, amortization, hospital administration etc. The total expenditure for a 10-15-day treatment of the acute neurological incident depended on the severity of the disease and was 8 million ++ zloty in case of mildly ill patient, 9 million in case of moderately severe disease, and 21 million zloty in case of severely ill patient. If the costs of such tests as CT and TCD-scanning will be added, total cost will increase significantly. PMID- 1437747 TI - [Computerized tomography in the diagnosis of hemorrhage caused by ruptured intracranial aneurysm]. AB - The authors presented current views on usefulness of computed tomography (CT) for diagnosing the bleeding from a ruptured intracranial aneurysm. CT should be done in every such case, whereas the lumbar puncture remains the diagnostic method of choice, when CT is not available or in those patients in whom CT shows no haemorrhage. Sensitivity of CT decreases with time that elapsed from the stroke; false negative results are the least likely to occur within the first 48 hours after bleeding episode to subarachnoid space. PMID- 1437748 TI - [Mathematical analysis of relations between dose, level or volume of bupivacaine and various hemodynamic parameters in epidural anesthesia]. AB - Changes in the basic, hemodynamic parameters during the first 30 minutes of epidural anesthesia in relation of the dose, concentration, and volume of bupivacaine used are discussed. It was found, that in a proper epidural anesthesia a significant effect on the value of basic hemodynamic parameters was exerted only by a volume of administered bupivacaine solution, whereas its concentration or dose do not play any significant role. However, further prospective studies are necessary to extend this observation on the wider population. PMID- 1437749 TI - [Outline of the history of the treatment of cerebral aneurysms]. PMID- 1437750 TI - [Compression fractures of the vertebrae in children with acute lymphoblastic leukemia]. AB - Compression fractures of vertebrae were noted in 20 out of 1,700 children with the acute lymphoblastic leukemia. Usually prognosis in these cases has been favourable (70% of patients are alive from 5 months to 19 years). Percentage of recovery from compression fractures has been relatively high. Lymphoblastic leukemia with infiltrations localized in the spine is relatively non-aggressive, develops slowly, and despite extensive lesions to the bones its outcome results are favourable. Main symptom of spinal involvement include severe and persisting back aches which make walking impossible. Such symptoms should indicate the diagnosis of leukemia and advocate proper hematological examinations. PMID- 1437751 TI - [Hybrid leukemia among acute childhood leukemias]. AB - Four children with the acute leukemia are presented. Their blasts shown the presence of 2 cellular lines markers. Coexistence of markers in the blasts was detected with the technique of double staining the blasts from the bone marrow with: alkaline phosphatase-anti-alkaline phosphatase, and peroxidase with the use of monoclonal antibodies series. Analysis of blasts phenotype with monoclonal antibodies confirm the occurrence of leukemias different from the normally programmed cellular line. Deviations of leukemic cells phenotype may be explained with the fact that leukemogenesis is not an absolute block of cells differentiation but combines maturation disorders and proliferation enabling expression normally absent antigens. It confirms the concept of line preservation and presentation of "earlier frozen" phenotype, and explains the occurrence of leukemias in which blasts present phenotype of one line which does not comply with cell differentiation pattern. Further genotypic studies are necessary to clarify pathogenesis and origin of such blasts. Consequently examination of the larger group of patients with hybrid leukemias will enable conclusions concerning prognostic value of such findings and necessity of introduction of the special therapies. PMID- 1437752 TI - [Recurrences after completion of the treatment of acute lymphoblastic leukemia in children]. AB - Within the past 16 years, 2004 children with the acute lymphoblastic leukemia were treated at the Centres of the Polish Pediatric Study Group. The treatment was completed in 887 patients (44.3%) with the first remission. Recurrence was noted in 180 children (20.3%). This group was analysed in view of the type of therapy and its effect on the survival rate, significance of recurrence following therapy, character and localization of recurrent disease, and further fate of patients. It was found, that patients with isolated late nuclear recurrence have greatest chances to achieve subsequent remission. Most frequent and severe is recurrent bone marrow involvement which requires intensive chemotherapy combined with bone marrow transplantation due to unfavourable prognosis. Patients with the first recurrence of the acute lymphoblastic leukemia have a chance to achieve subsequent remission and long-term survival. PMID- 1437753 TI - [Activity of natural cytotoxic cells in non-Hodgkin's lymphoma]. AB - Cytotoxic activity of NK cells in the peripheral blood has been determined in 30 patients with malignant non-Hodgkin lymphomas prior to and following therapy. In the whole group as well as in subgroups classified according to the criteria of Working Formulation as lymphomas of the low, moderate and high degree of malignancy, activity of NK cells has been statistically significantly lower than that in healthy individuals. Marked increase in this activity has been noted in 19 patients in the state of clinical remission after the treatment with cytotoxic agents, and sometimes radiotherapy. The value of mean cytotoxic activity reached normal limits in the lymphoma of high degree of malignancy, and exceeded these limits in the lymphomas of moderate and low malignancy. PMID- 1437754 TI - [Prognostic value of the reaction to steroids in the treatment of acute lymphoblastic leukemia in children]. AB - Relationship between the result of therapy in 48 cases of the acute lymphoblastic leukemia in childhood and character of response to corticosteroids, classified according to BMF group, has been assessed. Follow up period ranged from 13 to 75 months (mean 36 months, median 39 months). In was found, that the probability of survival free from any events, probability of complete remission persistence, and probability of survival after diagnosis have been statistically significantly higher in the group of patients with positive response to corticosteroids in comparison with patients non-responding to these agents. However, there was no significant difference in the number of recurrencies with the involvement of CNS. Authors share the opinion that their results confirm an opinion of Riehm et al. that the response to corticosteroids is of prognostic value in the acute lymphoblastic leukemia in childhood. PMID- 1437756 TI - [Chromosome aberrations as a prognostic factor in children with acute lymphoblastic leukemia]. PMID- 1437755 TI - [Spastic paralysis of the lower extremities as the first symptom of acute myeloblastic leukemia]. AB - A case of acute myeloblastic leukemia (AML) with spastic paralysis of the lower extremities caused by a tumor of the spinal cord as the first symptoms of the disease is presented. The tumor consisted of leukaemic cells. A diagnosis of AML type M2, according to FAB classification, was established. A complete remission was achieved after 2 courses of chemotherapy. Patient started to walk after intensive rehabilitation. After 14 months of complete remission, recurrence was observed despite an intensified therapy. PMID- 1437757 TI - [Prognostic factors in chronic lymphocytic leukemia]. PMID- 1437758 TI - [Natural factors inhibiting blood coagulation (antithrombin III, protein C and protein S)]. PMID- 1437759 TI - [Physician's talks with patients and their relatives]. PMID- 1437760 TI - [The venous and lymphatic systems of human brain]. PMID- 1437761 TI - [Hyponatremia after subarachnoid hemorrhage caused by ruptured intracranial aneurysm]. AB - Hyponatremia developed both prior to and after surgery in 30.5% and 23.4% out of 164 patients with ruptured intracranial aneurysms. It was more frequent postoperatively in those patients in whom baseline serum sodium levels were lower. Hyponatremic patients were older than normonatremic. The mean difference in age was about 7 years. The authors, basing on CT scans, have found that hyponatremia development has been more likely in patients with blood visible in subarachnoid space, specially chiasmatic cistern, and patients with ventricular bleeding or hydrocephalus. Hyponatremia following subarachnoid hemorrhage seems to result from the ischemic lesions to hypothalamus i may, therefore, be considered as vegetative equivalent of so-called cerebrovascular spasm. PMID- 1437762 TI - [Experience with nimodipine treatment of vascular spasm after subarachnoid hemorrhage]. AB - Pathogenesis of vasospasms following subarachnoid haemorrhage and possible therapeutic efficacy of nimodipine (calcium channel blocking agent) are discussed. The authors present their own experience in the treatment of 209 patients with subarachnoid haemorrhage with nimodipine. Collected clinical results suggest the necessity of the combined treatment of vasospasm following subarachnoid haemorrhage with nimodipine, hypervolemia, and hypertensive agents. PMID- 1437763 TI - [Health resort treatment of eye diseases caused by ischemia]. AB - The authors discuss the results of ophthalmodynamometric tests used for the assessment of cerebro-retinal vessels reactivity following carbon dioxide baths and "peat collars". An analysis of systemic and local blood pressure in the ophthalmic artery measured with Weigelin and Lobstein technique enables to assess changes in blood pressures following a/m balneologic procedures. It was found that blood pressure does not change parallelly due to the mechanism of cerebral autoregulation. Transient decrease in blood pressure in the ophthalmic artery is produced by the dilatation of the internal carotid artery indicating a potent vasodilating action of carbon dioxide. PMID- 1437764 TI - [Study of etiopathogenesis of keratoconus with special reference to intraocular pressure]. PMID- 1437765 TI - [Treatment of patients with lysosomal storage diseases]. AB - A problem of management of patients with lysosomal storage diseases in own experience with over 100 children with such diseases has been discussed. Symptomatic therapy of carpal tunnel syndrome, Pudenz valves, splenectomies, plasty of hernia, locomotive rehabilitation and various forms of cooperation with patients' families have been used in the treatment. An attempt of the treatment of the storage diseases with implantation of fetal membranes has been undertaken in view of the fact, that such membranes are the source of deficit enzyme. PMID- 1437766 TI - [Nutrition of patients after cranial injuries]. PMID- 1437767 TI - [Results of the treatment of Wilson's disease with zinc sulfate and d penicillamine]. AB - Nine patients with newly diagnosed Wilson's disease were treated with zinc sulphate for 12 months. Polish preparation Zincteral was administered in doses of 200 mg 4 times daily. The neurological status has improved in five cases. No adverse reactions of zinc sulphate were observed. The results were compared with the therapeutic effect, obtained in the group of 10 patients who received d penicillamine (Cuprenil-Polfa) 1.0-1.5 g daily from the very beginning. In three cases drug was discontinued due to adverse reactions. In remaining seven cases, in five evidence of the clinical improvement of the neurological status was observed, but in one case during 12 months of observation progressing deterioration was noticed. Neurological state of one patient remained unchanged. PMID- 1437768 TI - [Use of the transcranial Doppler ultrasonographic diagnosis in neurology and surgery]. PMID- 1437770 TI - [Computer-assisted analysis of patients' medical records]. PMID- 1437769 TI - [A few remarks regarding 421 cases of trigeminal neuralgia]. AB - Referring to the treatment of 421 patients with trigeminal neuralgia, the authors indicate an early alcoholization or exheyresis in case of therapeutical failure of systemic conservative treatment. Such a management prevents transformation of the peripheral into central neuralgia. Emphasis is on more frequent treatment of neuralgia by dental surgeons. PMID- 1437771 TI - [The QT interval--its clinical significance]. PMID- 1437772 TI - [Usefulness of the measurement of corrected QT (QTc) for the diagnosis of diabetic neuropathy of the autonomic cardiovascular system]. AB - Corrected QT interval was determined in diabetic patients and in a group of obese individuals with glucose intolerance. It was shown that the measurements of corrected QT (QTc) interval may be a reliable test in the diagnosis of the autonomic diabetic neuropathy. Its simplicity enables routine measurements in diabetic patients treated in out-patients clinics. PMID- 1437773 TI - [Time of regression of the Q wave in patients with myocardial infarction]. AB - A rate of Q wave regression was assessed in 72 patients with ischaemic heart disease, including 46 patients after the infarction of the inferior wall and 26 patients after anterior wall infarction. All patients were followed-up for two years. Complete regression of Q wave was noted in 19 patients (41.3%) after inferior wall infarction and in one patient (3.8%) after anterior wall myocardial infarction. Partial regression of Q wave was seen in 9 patients (19.6%) after inferior wall, and in 2 patients (7.6%) of patients with anterior wall myocardial infarction. It seems that the regression of Q wave in ECG does not improve prognosis in these patients. Six out of 10 deaths which occurred in the followed up group of patients involved those in whom no electrographic features of the past myocardial infarction were seen. PMID- 1437774 TI - [Programmed atrial and ventricular stimulation in patients with mitral valve prolapse--a personal experience]. AB - Electrophysiological tests were performed in 60 patients aged between 18 and 63 years (mean age 38 years), and divided into two groups: with mitral valve leaves prolapse syndrome, and without this abnormality, in whom no other heart disease was diagnosed. Refraction of the right atrium, atrio-ventricular node, and right ventricle was evaluated together with cardiac response to different types of electrostimulation. A supraventricular dysrhythmia (most frequently atrial fibrillation) has been produced in 17 patients (42.5%) with mitral valve leaves prolapse syndrome whereas in the control group the same was produced in 2 patients (10%). Programmed stimulation of the ventricles did not produce ventricular tachycardia in none patient of both groups. Multiple ventricular beats have been produced in 3 patients with mitral valve prolapse syndrome and pairs of ventricular beats in other 3 patients of this group. Results suggest that "arrhythmogenic tendency", especially supraventricular dysrhythmia is more frequent in patients with mitral valve prolapse syndrome than in the general population. PMID- 1437775 TI - [Magnesium and potassium levels in the blood serum and lymphocytes and the rate of sodium outflow through lymphocyte membranes in patients with chronic heart failure]. PMID- 1437776 TI - [Analysis of the causes and clinical course of anemia in elderly patients]. AB - Anamnesis of patients treated for anemia at the Department of Internal and Occupational Diseases in Zabrze in 1984-1988 were analysed. It was found that the incidence of anemia in patients over 60 years of age was significantly higher. Decreased function of hematopoietic system, more frequent deficits of factors indispensable for the normal erythropoiesis, i.e. iron and vitamin B12, and coexisting diseases, especially neoplasms and uremia, predispose to anemia in this age group. Anemia seen in the group of patients with diabetes mellitus type 2 was most probably a result of the chronic treatment with sulfonylurea derivatives. PMID- 1437777 TI - [Propionibacterium acnes in the etiology of endocarditis]. AB - Propionibacterium acnes is the gram positive anaerobic bacteria belongs to the normal skin and oral microbial flora. The participation of this microorganism in the infective endocarditis is still controversial. The aim of the study was to perform the diagnostic and therapeutic difficulties in 5 patients with infective endocarditis caused by Propionibacterium acnes. In 3 out of 5 patients the infective endocarditis developed after prosthesis valve replacement, in 2 others on the native valves. The inserted prostheses were mechanical ones, propionibacterium acnes was identified as causative organisms in all of the causes (two positive blood and/or valve culture). The bacterial strains were sensitive to the antibiotics as: penicillins, cephalosporins, clindamycin, and vancomycin, however cephalosporins used at the beginning of the treatment in 3 patients and clindamycin in 1 patient had limited clinical efficacy. Later treatment with timentin, augmentin and tienamycin was successful in 3 patients; one patient was cured with vancomycin. One patient died because of septic, embolic complication in early stage of illness. We conclude the effectiveness of penicillins in combination with clavulanic acid and tienamycin in therapy of infective endocarditis due to Propionibacterium acnes. The treatment should be lasted during 4-6 weeks. PMID- 1437778 TI - [Emergency epicardial dissection of the accessory pathway in a patient with atrioventricular nodal reentrant tachycardia]. AB - Diagnostic and therapeutic problems in 14 year old patient with concealed WPW syndrome were presented. Paroxysms of atrio-ventricular reentrant tachycardia 180 220/min were frequently recurring, usually with normal QRS pattern. Tachycardias often had to be terminated by intravenous administration of antiarrhythmic drugs. Long term treatment with various antiarrhythmic agents did not prevent recurrence of tachycardias but they became sustained and were recurring more often. Their other side effects manifested with sinus node disfunction and depression of the heart muscle. The electrophysiologic study revealed right anterior septal accessory pathway. Epicardial dissection of the accessory pathway was urgently performed. The control electrophysiologic study revealed no evidence of conduction through the accessory pathway. The patient did not require antiarrhythmic treatment. During the 12 months follow up no tachycardia occurred. PMID- 1437779 TI - [Cardiological and endocrinological complications after bone marrow transplantation]. PMID- 1437780 TI - [Endothelium-derived relaxing factor (EDRF)]. PMID- 1437781 TI - [Dioxins]. PMID- 1437782 TI - [Daily fat consumption by the population of Warsaw]. AB - Fat intake with the diet has been assessed within screening Pol-MONICA--Warsaw Project in randomly selected sample of Warsaw inhabitants aged between 35 and 64 years. Altogether 2571 individuals have been screened. Fat intake in daily diet has been estimated by the 24-hour recall technique. In men, fat intake covered 38.4% of the total energy supply with the diet whereas in female population - 37.7%. Mean contribution of SFA and P/S ratio in both sex groups have been 15.8% and 0.285, respectively. Daily cholesterol intake has been 641 mg (224 mg/1000 kcal) in male and 456 mg (227/1000 kcal) in female population. These values did not change significantly with the age of the screened individuals. Such a diet may be considered atherogenic. PMID- 1437783 TI - [Cardiological problems in Warsaw in the first half of the 19th century]. PMID- 1437784 TI - [Evaluation of the activity of ulcerative colitis]. PMID- 1437785 TI - [General practice as the basis of health care in the society. General concepts of primary health care]. PMID- 1437786 TI - [In memory of an unusual physician (on the 50th anniversary of death of pediatrician Tadeusz Zelenski]. PMID- 1437787 TI - [The first gastroenterologic society in Europe]. PMID- 1437788 TI - [Biliary scintigraphy]. PMID- 1437789 TI - [Anatomic changes in the biliary tract and pancreas in patients with diabetes mellitus diagnosed by endoscopic retrograde cholangiopancreatography]. AB - Structural changes in both biliary tract and pancreas have been assessed with endoscopic retrograde cholangiopancreatography in 100 diabetic patients divided into subgroups depending on the type of diabetes mellitus, i.e. type I, type II and III-pancreatic. Control group included 100 randomly selected patients without diabetes mellitus in whom endoscopic retrograde cholangiopancreatography has been performed for various indications. Structural changes in the biliary tract and pancreas have been more frequent in diabetic patients than in the control group (47 and 75% vs 32 and 30%, respectively). Cholelithiasis has been noted in 27.8% of patients with type II diabetes mellitus and in 11.3% of patients with type I diabetes mellitus; obesity has been found in 57 and 12% of patients, respectively. Other biliary tract disorders, mainly in the form of segmental stenosis or dilatation of the common bile duct, have been more frequent in patients with type II diabetes mellitus. Pancreatic disorders, assessed with the aid of Cambridge classification, have been noted in all patients with pancreatic diabetes and in 80.7% of patients with diabetes mellitus type I. Incidence of so called doubtful and mild disorders has been more frequent (22.2 and 24.1%, respectively) in patients with diabetes mellitus type II whereas "moderate" and "severe" disorders have been significantly less frequent (7.4 and 1.9% of patients). The results indicate, that endoscopic retrograde cholangiopancreatography is useful in the assessment of bile ducts structure and pancreatic exocrine activity in diabetic patients in whom disorders are more frequent. PMID- 1437790 TI - [Effect of colloid bismuth treatment on Campylobacter pylori infection of the gastric mucosa and the clinical course of non-ulcer dyspepsia]. AB - There are suggestions, that the idiopathic non-ulcer dyspepsia is related to the chronic gastritis type B coexisting with C. pylori infection. Presented studies were aimed at the assessing of an effect of the treatment with De-Nol on the course of the idiopathic non-ulcer dyspepsia of C. pylori infection. Gastroscopic examination was performed in 52 patients with non-ulcer dyspepsia before and after the treatment with De-Nol administered for 4-8 weeks. Campylobacter pylori was isolated from 71% of patients with idiopathic non-ulcer dyspepsia. An infection was eradicated in 97.4% of patients treated with De-Nol. The number of dyspeptic episodes decreased in by 96% of patients, including 33% of patients in whom total recovery was noted. De-Nol was well tolerated. De-Nol is highly effective in the eradication of C. pylori and produces clinical improvement in the majority of patients with non-ulcer dyspepsia. PMID- 1437791 TI - [Inflammatory changes in the gastric mucosa of patients with idiopathic non-ulcer dyspepsia and the effect of colloid bismuth treatment on the course of inflammation]. AB - The studies were aimed at the assessment of the coexistence of non-ulcer dyspepsia with chronic gastritis and Campylobacter pylori infection, and of the effect of therapy with De-Nol on the course of such disease. The studies involved 50 patients with non-ulcer dyspepsia. Prior to and after the treatment with De Nol samples of the mucosa collected from the antrum and corpus of the stomach have been examined histologically with urease test indicating C. pylori infection. Chronic gastritis of the antral mucosa membrane and/or mucosa of the corpus of the stomach has been found in 36 patients, and normal mucosa in 14 patients. Therapy with De-Nol produced statistically significant improvement. Totally histological improvement has been noted in 77.1% of patients with inflammation of the antral mucous membrane and in 64.3% of patients with inflammation of the corporeal gastric mucosa. Campylobacter pylori has been eradicated in all patients with chronic gastritis. De Nol eliminates or significantly lowers an inflammation in the antrum and/or corpus of the stomach. Its action is related to the eradication of Campylobacter pylori infection. PMID- 1437792 TI - [Effect of the Warren operation on hypersplenism]. AB - The authors present their own comments on the effect of Warren shunt on hypersplenism. Hypersplenism is frequent complication in portal hypertension. The authors estimate its frequency on 64.7% of patients. Spleen size, thrombocyte count, WBC count, and esophageal endoscopy have been carried out prior to and following distal spleno-renal shunt. Surgery produced favourable effect in 70% of patients, i.e. a decrease of hypersplenism symptoms. An increase in blood platelet count may serve as a screening marker of anastomosis patency. PMID- 1437793 TI - [Serum triiodothyronine and thyroxine levels in children with celiac disease]. AB - The study was aimed at determining relationship between thyroid function and the type and degree of malabsorption. Serum triiodothyronine (T3) and thyroxine (T4) levels were determined in children with celiac disease and the secondary malabsorption. Hundred fifty five children aged between 6 months and 7 years were followed up 3 years. Coeliac disease was diagnosed with classic Interlaken criteria. All children were divided into three groups: group I--57 children aged between 6 months and 3 years with suspected celiac disease; group II--55 children aged between 2.5 and 6 years after gluten-free diet therapy; group III--52 children aged between 3 and 7 years after gluten provocation test. Serum T3 and T4 levels for each group were compared with those in children with normal gut mucous membrane. Blood serum T3 and T4 were assayed with OPIDI kit (manufactured in Swierk). Serum T4 levels were significantly lower in children with mucous membrane atrophy in comparison with dystrophic children and normal gut mucous membrane. Both serum T3 and T4 were significantly lowered in the youngest children upto 12 months of life with mucous membranes atrophy. Serum T3 and T4 concentrations were below the normal values in 4 youngest children. Blood serum T3 and T4 levels did not depend on the morphology of the intestinal villi in children treated with gluten-free diet (some children did not observe the diet and had atrophic lesions to the mucous membrane of the small intestine). Blood serum T3 level was relatively increased in children of group II with mucous membrane regeneration; in comparison with the value determined in the period of active disease. PMID- 1437794 TI - [Patient monitoring after surgical treatment of cancer of the large intestine]. PMID- 1437795 TI - [Alpha 1-antitrypsin as an endogenous marker of protein-losing enteropathies]. AB - A novelty of the present studies is the use of alpha 1-antitrypsin (A-1--AT) as an endogenous marker of enteric protein loss. Enteric clearance of alpha 1 antitrypsin was determined in 10 patients with the symptoms of PLE, and in 6 healthy individuals. Alpha 1-Antitrypsin concentration has been assayed in single, random samples of feces collected from 42 patients and 12 healthy individuals (normal values: 1.31 +/- 0.72 mg/g of feces). Markedly increased enteric clearance and A-1-AT concentrations in single, random samples of feces have been found in patients with enteric lymphangiectasis, Crohn's disease, ulcerative colitis, and constrictive pericarditis, slightly lower in coeliac, chronic diarrhoea, nonspecific hemorrhagic colitis, esophagitis, lambliasis, hypogammaglobulinemia, Wiskott-Aldrich syndrome, Rendu-Osler-Weber syndrome, hepatitis in newborn, and Gilbert's disease. Statistically significant positive clearance has been noted (r = 0.997; p less than .001). A single assay of A-1-AT in feces is simple, repeatable, and sensitive technique in the diagnosis and evaluation of these diseases in which the symptoms of enteric protein loss are seen. PMID- 1437796 TI - [Intra-systemic inhibitors of the hematopoietic system]. AB - Physiological, experimental and theoretical aspects concerning haemopoietic inhibitors are reviewed. In the paper there are also discussed future research directions of this branch of haematology. PMID- 1437797 TI - [Blood coagulation and fibrinolysis in blood donors after plasmapheresis]. AB - Authors were interested in blood coagulation proteins and fibrinolysis in blood donors following several plasmaphereses. This interest was related to the occurrence of thrombo-embolic and hemorrhagic complications in these subjects. Blood morphology, serum protein, blood coagulation and fibrinolysis have been examined in 40 healthy blood donors, aged between 19 and 46 years, who gave blood plasma by plasmapheresis technique for 1-59 times. Results did not show any significant changes in blood morphology and serum protein levels prior to and after consecutive plasmaphereses. No significant decrease in blood coagulation proteins and fibrinolysis has been noted. However, a significant increase in factors VIII and IX activities was noted in several blood donors, who underwent the largest number of plasmaphereses. It may predispose these donors to thrombo embolic complications. PMID- 1437798 TI - [Evaluation of loss of active heparin in the peritoneal cavity during intermittent peritoneal dialysis]. AB - Our studies aimed at determining a loss of active heparin from the peritoneal cavity after its intraperitoneal administration (250 JU/l of dialysis fluid) in 16 patients treated because of the end-stage renal failure with intermittent peritoneal dialysis and at comparing heparin influx clearance with that of glucose. It has been shown that heparin used in this dose loses 60-70% of its activity after 20-minute equilibration of dialysis fluid in the peritoneal cavity. Heparin influx clearance is higher than that of glucose but it depends on utilization of heparin in peritoneal cavity rather than on its penetration to the blood circulation. PMID- 1437799 TI - [Effect of ethyl alcohol on selected parameters of the hemostasis system in vitro]. AB - Alcohol produces several disorders in all components of hemostasis system. However, its mechanism of action is not clear. Therefore, an effect of ethyl alcohol on the selected parameters of both platelet and plasma hemostasis has been examined in vitro. Blood aggregation induced by ADP and PAF and platelet leucocytic aggregates have been determined in vitro in the group of 45 healthy volunteers. Out of plasma parameters the selected factors of blood coagulation and fibrinolysis have been examined. Results suggest that the examined concentrations of ethyl alcohol mainly affect platelet function decreasing platelet aggregation. Alcohol does not affect significantly blood coagulation and fibrinolysis occurring in vitro. PMID- 1437800 TI - [Diarrhea caused by Campylobacter in patients with hematologic diseases]. AB - Diarrhoea caused by Campylobacter infection in two adult patients was observed: one with erythroleukemia, and another with non-Hodgkin lymphoma. An infection developed in both cases during the period of agranulocytosis and decreased specific immunologic response to cytostatics. In case of the second patient, it has also been due to the underlying disease. The course of the disease has been different in both patient. It was dramatic with high fever and multiple fetid stools in one patient, and mild, successfully treated within a few days, in the second. PMID- 1437801 TI - [Pancytopenia as a complication of the treatment of toxoplasmosis]. AB - Therapeutical doses of pyrimethamine are very close to toxic ones. Pyrimethamine is widely used in toxoplasmosis therapy. Hematological complications following pyrimethamine administration were seen in 4 patients treated for toxoplasmosis at our hospital in the last year. Pancytopenic syndrome was diagnosed in all four cases. Three patients recovered completely whereas ITP is persisting in one patient. PMID- 1437803 TI - [8 cases of thrombotic thrombocytopenic purpura]. AB - Eight cases of the thrombocytopenic thrombosis are presented. Etiological factors, prognosis, and actual therapy are discussed. An emphasis is on the significance of freshly frozen plasma administration in the treatment of this disease. PMID- 1437802 TI - [Familial occurrence of Glanzmann thrombasthenia]. AB - Glanzmann's thrombasthenia, known also as Glanzmann's disease, is an autosomally inherited hemorrhagic disease with unique abnormalities of platelet functions. Authors present a large family in which Glanzmann's disease was diagnosed in the father and two sons. An analysis of platelet membranes enabled diagnosis of Glanzmann's thrombasthenia type II. A decrease in clot contractibility, fibrinogen binding to blood platelets, and decreased glycoprotein IIb and IIIa levels with marked impairment of GP IIb and IIIa complexes formation were characteristic for affected family members. One daughter died 8 days after birth with the symptoms of hemorrhagic diathesis. Mother and remaining three sons are healthy without the signs of Glanzmann's disease. PMID- 1437804 TI - [Current views on the pathogenesis and treatment of spontaneous (primary) myelofibrosis]. PMID- 1437805 TI - [Lupus anticoagulant--its role and significance in the pathogenesis of thrombosis]. PMID- 1437806 TI - [Lupus anticoagulant as a risk factor of thrombosis]. PMID- 1437807 TI - [The place of empathy in the undergraduate training of physicians]. PMID- 1437808 TI - [Current status and advances in present-day radiology]. PMID- 1437809 TI - [Embolization of the branches of the external carotid artery]. AB - Authors present their own experience with the embolization of the external carotid artery branches. The main indications to embolization included well vascularized and hemorrhagic brain tumors in facial part of the skull, mainly meningiomas, juvenile angiofibromas, and angioneuromyomas. Embolization of external carotid artery was performed in 15 patients. Complete impatience of blood vessel supplying the tumor was achieved in 12 cases, but it was incomplete in 3 cases. Single serious complication in the form of hemiplegia was noted. There were also mild complications in 5 patients, which did not require any intervention. PMID- 1437810 TI - [Use of high resolution algorithm in computerized tomography of disseminated lung diseases]. AB - Lobule of the lung is a principal anatomical structure of the respiratory zone in the lungs. Secondary lobule of the lung consists of about fifty primary lobules and is delineated by fibrous interlobular septa. Each lobule is delineated by interlobular septa and blood is supplied by small arterioles of pulmonary artery system. Its shape is conical and size ranges from 10 to 22 mm. The author used algorithm of high resolution in HR CT to present normal distal generations of respiratory area of the lungs and the same in 32 patients with disseminated lesions to the lungs. It is known, that lobule of the lung may be involved in very important pathologies. The author shown that significant architectural rearrangement takes place in pulmonary lobules and adjacent areas in the course of disseminated pulmonary diseases. The process include thickening of interlobular septa, consolidation of lobular area, changes in the shape of lobuli, and appearance of small cysts. The use of HR CT enables imaging in such pathologies which normally are inaccessible to conventional radiologic examinations. PMID- 1437811 TI - [Filling of the lower segment of the large intestine with fluid to facilitate ultrasonic examination in diseases of the small pelvis]. AB - Small pelvis space is difficult to examine ultrasonographically as several important organs are localized in relatively small area. The most difficult is the interpretation of the standard USG examination of the abdomen in case of pathologies of the end of large intestine, when filled with feces. In such cases repeated ultrasonographic examination is recommended. Authors propose, that this segment of the colon should previously be filled with fluid. Such a technique improves the level of diagnosis or exclusion of any pathology. Forty two patients were examined with the above technique. Authors think, that it is a progress in ultrasonography of pelvic organs. PMID- 1437812 TI - [Usefulness of biliary scintigraphy using technetium Tc 99m mebrofenin for detection of disorders of patency of the bile ducts]. AB - The value of the dynamic 99mTc-mebrofenin liver scintigraphy in the diagnosis of extrahepatic bile ducts patency has been assessed. The study included 176 patients in whom an occlusion of bile ducts of any degree was excluded in 111 cases, and bile ducts patency disorders were diagnosed in 65 patients. Time of the appearance of radiolabelled mebrofenin was measured in the selected segments of bile ducts. Time of appearance of radioactivity in the intestines was also noted. Another diagnostic criterion was persistent stasis of radioactivity in the choledochus. Basing on these criteria, patients were classified as "sick" or "healthy". It was possible to exclude the disease in case of negative result with the probability level of 91%. Positive result of scintigraphy points to the impaired patency diagnosis with 96% probability. Technique is simple, free of complications and contraindications. It is also of high predictive value. These features make the procedure particularly useful in the diagnosis of bile ducts patency. PMID- 1437813 TI - [Recanalization of occlusion of the peripheral segment of the femoral artery by the Kensey method]. AB - The aim of the presented study was to analyse the surgical technique and results of recanalization of the peripheral segment of iliac artery with Kensey's technique. Altogether 16 patients were operated. Arterial patency was observed in 14 patients immediately after surgery. This number decreased to 11 after a 3 month follow-up. Complications in the form of perforation of the arterial wall, hemorrhage at the site of puncture and thrombotic lesions in the reconstructed arterial channel were seen in 4 cases. Authors' own experience suggests that Kensey's technique together with laser surgery are the treatment of choice in case of iliac arterial occlusion in patients, in whom classic surgery is contraindicated. PMID- 1437814 TI - [Quantitative computerized tomography as a method of estimating calcium level in the bones]. PMID- 1437815 TI - [Radioisotope functional studies of the central nervous system]. PMID- 1437816 TI - [Immunoscintigraphy--its value in the radioisotope diagnosis]. PMID- 1437817 TI - [Radioisotope examination of myocardial blood supply using Tl-201 in the diagnosis of coronary disease]. PMID- 1437818 TI - [Diagnosis of choledochal cysts in children with special reference to ultrasonographic examination]. AB - Early diagnosis of the choledochal cysts in childhood, especially obstructing bile outflow to the duodenum, is an important clinical problem; often leading to serious complications--if not treated. Authors treated 5 children with choledochal cysts. Three out of them have been treated surgically. Ultrasound examination is sufficient to diagnose the disease, if the cyst is connected with intrahepatic bile ducts. If such a case is not possible to be imaged, cholescintigraphy and thin-needle biopsy with contrast filling are necessary to confirm the diagnosis. PMID- 1437819 TI - [Quo vadis, ultrasonography?]. PMID- 1437820 TI - [Bone marrow transplantation in the treatment of various genetically determined diseases]. PMID- 1437821 TI - [Cytogenetic studies in fragile X syndrome]. AB - The main purpose of this work has been to find a method which would enable the diagnosis of FXS at the cytogenetic level. The studies are based on the analysis of chromosomes from 24 cultures on RPMI-1640 base with an addition of 5-fluoro-2' deoxyuridine (FUdR) as inhibitor of thymidylate synthetase. The results indicate, that the cultures with the addition of FUdR could considerably improve the expression of fragile X chromosome. It is of great importance, particularly un the cases in which the presence of this marker is very low. It was possibly to specify the significant percentage and the exact position of breaks, gaps and fragile sites, mostly present in autosomes. It could mean, that such factors may play a significant role, apart of X chromosome, in the pathogenesis of FXS. The results of work prove, that this kind of method could be used as a screening for cases with fragile X syndrome. PMID- 1437822 TI - [Evaluation of the phenylalanine tolerance test in detection of heterozygote carriers of phenylketonuria gene]. AB - The study aimed at identifying heterozygotic phenylketonuria gene carriers with phenylalanine tolerance test performed in Lublin region. Serum phenylalanine concentration has been assayed during fasting and 1 and 2 hours following oral phenylalanine load in the dose of 0.1 g per 1 kg body weight. The study involved 203 individuals of the general population and 29 heterozygotes with phenylketonuria gene. Blood serum phenylalanine was assayed with Guthrie' technique. Statistical analysis has shown that hyperphenylalaninemia is relatively frequent in fasting individuals of the general population (59.1%). The same was demonstrated in 5 heterozygotes. Phenylalanine tolerance test did not allow to identify heterozygotic carries of phenylketonuria gene in the general population though fasting and after phenylalanine load increased blood serum levels of this amino acid are a criterium of hyperphenylalaninemia in the group of tested individuals (29%). PMID- 1437823 TI - [Minutiae of skin ridges in Down's syndrome]. AB - Minutiae of the epidermal ridges were examined in 16 children with Down's syndrome and 50 children without genetic and familial abnormalities. Minutiae in standard areas on the hand palms (according to Grzeszyk's concept) were examined. Comparative analysis confirmed by the statistical analysis showed significant differences in the incidence of particular minutiae types on the hand palms of children with Down's syndrome and control group. PMID- 1437824 TI - [Correctness of diagnosis of celiac disease based on personal data]. AB - A way of coeliac disease diagnosis was assessed in 348 children, Only 14% of patients has been examined according to ESPGAN recommendations and in the proper time. Diagnosis has been completed in 123 patients, and coeliac disease has been diagnosed only in 38 of them. The I biopsy has not been performed in 96 children, the II biopsy--in 136 children, gluten-free diet has not been observed in 105 children after the I biopsy. Other causes of diagnostic failures included: prolongation of the consecutive stages and improper histological evaluation, change of biopsies order, erroneous clinical evaluation. Diagnosis according to ESPGAN recommendations is practically very difficult and time consuming. Immunological markers of coeliac disease (IgA EmA, ARA) should lead to simplification and adjustment of those recommendations in Poland. PMID- 1437825 TI - [Clinical course of congenital toxoplasmosis in children]. AB - Hundred eleven children with the congenital toxoplasmosis were treated at the Department of Infectious and Parasitic Diseases in Childhood in 1979-1988. Multi symptomatic toxoplasmosis has been diagnosed in 35 cases, ocular form in 65, oligosymptomatic in 6, and asymptomatic in 5 cases. Clinical symptoms suggesting congenital toxoplasmosis was seen in the majority of children (63 cases) in the first year of life and the disease was diagnosed in 50% of cases (33 children) at this age. Congenital toxoplasmosis in the group of 78 children has been diagnosed later. The majority of cases was ocular form. Diagnosis of the oligo- and asymptomatic congenital toxoplasmosis is possible in the first year of life, only. A titre of antibodies is exclusively an indicator of the immunologic response, not a severity of infection and does not contribute to the prognosis. Antitoxoplasma drugs were administered to 102 children including 33 under the first year of life. Pyrimethamine, sulphonamides, and spiramycin were used in the treatment. Dosage, duration of therapy, and way of administration have been established individually in dependence of patients age and clinical form of the congenital toxoplasmosis. Two out of 35 children with multi-symptomatic congenital toxoplasmosis died whereas 13 demonstrate psychomotor retardation of significant degree despite the fact that 11 of them were treated in the first year of life. PMID- 1437826 TI - [Observations of children with chorioretinitis in congenital toxoplasmosis]. AB - Hundred eleven children with congenital toxoplasmosis were followed up in the Department of Infectious and Parasitic Diseases in Childhood, Medical Academy in Warsaw, within 1979-1988. Ocular changes found in 91 children including chorioretinitis in 86 microphthalmia in 7, ophthalmic nerve atrophy in 15, vitreous body inflammation in 5, and cataract in 4. Only in 16 children the diagnosis was performed in the first year of life. In 15 children the recurrence of inflammatory process, most frequently in the time of puberty, was noted; twice in 5 of them. It was independent on the treatment which was previously administrated. Serological tests in ocular form of congenital toxoplasmosis do not indicate the dynamic changes in the inflammatory process. It is very important that small children are examined early and the treatment is started in the first year of life. PMID- 1437827 TI - [Ullrich-Feichtiger syndrome in a 3-year-old boy]. AB - A case of a 3 year old boy with Ullrich-Feichtiger syndrome is presented, because of the rarity of this syndrome. Ullrich-Feichtiger syndrome diagnosis was based on the following clinical signs and symptoms: a) micrognathia with several teeth developmental abnormalities; b) polydactyly (six toes); c) varied genital malformations; d) multiple ocular abnormalities. Cause of these multiple malformations remains unclear. PMID- 1437828 TI - [Atypical form of phenylketonuria caused by lack of dihydrobiopterin synthetase activity]. AB - A case of non-typical phenylketonuria produced by the inactivity of dihydrobiopterin synthetases is presented. Dihydrobiopterin synthetases are enzymes converting neopterin to biopterin. Presented case indicates a possibility of erroneous classification of hyperphenylalaninemia due to BH4 deficit, if the complete differential diagnosis is not performed. A complete differential diagnosis is necessary in all cases of hyperphenylalaninemia distinguished in neonates during screening tests. PMID- 1437830 TI - Primitive neuroepithelial tumors with vermiform processes (filiform neuroepithelial tumors). Immunocytochemical and ultrastructural study of 2 cases. AB - Two unique, poorly-differentiated neuroepithelial tumors are described, one in a 35-year-old woman with an anterior mediastinal tumor and one in a 71-year-old woman with a left femoral mass. Immunocytochemical stains demonstrated Neuron specific enolase in both tumors and Chromogranin in one. Electron microscopy showed the cells of both neoplasms to contain abundant, thick, vermiform, organelle-free processes, previously described solely in large cell lymphomas. Rare dense-core granules were present, and very few processes were suggestive of neurites. These observations enlarge the spectrum of poorly differentiated neuroepithelial tumors. PMID- 1437829 TI - [Students' views on the need to humanize medical studies]. PMID- 1437831 TI - Distribution of tissue markers in acinic cell carcinomas of salivary gland. AB - Eight cases of acinic cell carcinoma of the salivary glands were histologically reclassified and their immunohistochemical expression and distribution for various tissue antigens were examined. The epithelial elements were divided into tubuloglandular components, microcystic patterns and solid nests. The authors' results indicated the following: 1) The duct luminal cells of tubuloglandular components have distinct epithelial features with cytokeratin (KL 1), alpha 1 antichymotrypsin (alpha 1-ACT), transferrin, lactoferrin, IgA, and carcinoembryonic antigen (CEA) positivity. 2) The cyst-lining cells of microcystic pattern expressed immunophenotypes similar to those of the duct luminal cells. 3) The acinic cells in solid nests had positive results for KL 1, alpha 1-antitrypsin (alpha 1-AT), transferrin, lactoferrin and vasoactive intestinal polypeptide (VIP). 4) The clear cells in solid areas had positive results for KL 1, alpha 1-AT, transferrin and VIP. Both the clear cells and the neoplastic acinic cells showed a rather similar pattern of immunoreactivity. Therefore, the clear cells may transform from the neoplastic acinic cells. 5) Secretory products in tubuloglandular and microcystic patterns had positive results for alpha 1-ACT, lactoferrin, IgA and CEA. 6) The basement membrane-like material between the neoplastic islands has distinct positivity for alpha 1-AT. The result suggests that alpha 1-AT is a useful marker of basement membrane-like material. PMID- 1437832 TI - Immunohistochemical examination of routinely processed bone marrow biopsies. AB - Immunohistochemistry was performed on paraffin sections of 169 bone marrow biopsies fixed in a buffered methanol-formalin solution and decalcified with EDTA. The biopsies included specimens with normal hematopoiesis, and specimens that were affected by various hematological disorders as well as some metastatic carcinomas. The results demonstrate that a wide spectrum of antigens was preserved in routinely processed bone marrow biopsies, even after long-term fixation up to 12 days. Markers for granulopoietic cells were lysozyme, elastase, DAKO-M 1, and MT 1. Megakaryopoiesis was stained with glycoprotein IIIa, von Willebrand factor, and Ulex europaeus agglutinin (UEA), and erythropoiesis with LN 1. Normal lymphocytes as well as lymphoma cells of all non-Hodgkin's lymphomas tested were positive for leukocyte common antigen (LCA), and at variable degree, for MB 1, 4 KB 5, LN 1, LN 2, UCHL 1, or MT 1. Reed-Sternberg and Hodgkin's cells in Hodgkin's lymphomas were reactive with Ber-H 2, LN 2 and Dako-M 1. In plasma cell disorders, staining for immunoglobulin light chains gave best results. Metastatic carcinomas showed predominantly staining with EMA, and KL 1. A selected panel of specific cell markers is proposed, which proved to be helpful in routine bone marrow diagnosis in most cases. PMID- 1437833 TI - Cryopreservation of cytological specimens for immunocytochemistry. AB - A method has been established for storage and preservation of cytological specimens in liquid nitrogen and further processing for immunocytochemistry as smears prepared from thawed cells or cryo-sections of frozen cell pellets. For the experiments cultured cells of a T-lymphoblastic leukemia cell line (ATCC CCL 119) and blood cells of the buffy coat of healthy humans were treated with a cryo solution (fetal calf serum +5% dimethylsulfoxid) and after freezing stored in liquid nitrogen. Alternatively, cells preincubated with cryo-solution followed by suspension in fetal calf serum without cryo-additive were frozen and stored in liquid nitrogen for the production of cryo-sections. Indirect immunofluorescence and alkaline phosphatase--antialkaline phosphatase based immunoreactions were performed for the decoration of various surface antigens with a panel of monoclonal antibodies. All immunoreactions were repeated at least three times and the stored cell preparations were investigated after different periods of storage (up to four months). The immunoreactions of fresh cells in suspension (which were used as controls) were comparable with those of cryopreserved cells, e.g. cells on smears after thawing and on cryo-sections of cell pellets. The strongest immunoreactions were achieved on fixed cryo-sections. The maintenance of cell morphology of smears from cryopreserved cells was slightly better than of cells from cryo-sections. In our hands the preparation of cell pellets, which are suitable for the storage in liquid nitrogen and the production of cryosections, is a very useful method for immunocytochemical investigations of cytological specimens especially in situations where immunoreactions cannot be performed on fresh material.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437834 TI - Megakaryocytopoiesis in bone marrow biopsies of patients with acquired immunodeficiency syndrome (AIDS). An immunohistochemical and morphometric evaluation with special emphasis on myelodysplastic features and precursor cells. AB - In 25 patients (22 males, 3 females--median age 39 years) with AIDS (CDC stages IV A-D) and no preceding myelotoxic therapy, morphometry and immunohistochemistry (CD 61-Y 2/51) was performed on trephine biopsies of the bone marrow to evaluate the megakaryocytic lineage. In comparison with megakaryocytes in the myelodysplastic syndromes (MDS) significant differences were evident. In AIDS this cell population revealed a size distribution within the normal range (control group) and no predominance of micromegakaryocytes characteristic for MDS. Furthermore, by determination of the form factors more irregular shapes of cell and nuclear perimeters could be shown. Finally, a not-evaluated number of precursors (promegakaryoblasts) was calculable. Particularly in those patients (n = 15) with AIDS-related severe thrombocytopenia the missing increase in the relative amount of promegakaryoblasts was conspicuous. This result was strikingly different from findings in idiopathic (autoimmune) thrombocytopenia and suggested an impairment of progenitor cell proliferation and differentiation in the acquired immunodeficiency syndrome. In conclusion, morphometry in combination with immunohistochemistry failed to establish characteristic myelodysplastic aspects of the megakaryocytic lineage in AIDS. For this reason, bone marrow lesions in this disorder should be properly termed HIV-myelopathy and not myelodysplasia. PMID- 1437835 TI - Superficial extending carcinoma (SEC) of the larynx and hypopharynx. AB - In this study the histopathological features of an underestimated architectural variety of infiltrating squamous cell carcinoma of the larynx and hypopharynx, operationally termed as "superficial extending carcinoma", are described. Pathologically, the superficial extending carcinoma is a poorly/moderately differentiated infiltrating squamous cell carcinoma showing an entirely or predominant superficial type of growth; deep infiltration was confined to the mucosa or limited to a few underlying glandular and/or muscular laryngopharyngeal structures, regardless of the presence of lymph node metastasis or lymph vessel invasion. As defined above, the superficial extending carcinoma may be regarded, from a pathologic point of view, as a laryngopharyngeal counterpart to "superficial esophageal carcinoma". Studying a series of 88 whole organs serially sectioned laryngopharyngectomy specimens, we found that 6 out of 61 primary laryngeal carcinomas (9.8%) and 6 out of 26 primary hypopharyngeal carcinomas (23%) showed the peculiar architectural features of the superficial extending carcinoma. In 6 cases (2 laryngeal and 4 hypopharyngeal) the tumor was entirely intramucosal or early infiltrated the underlying muscle or gland structures. In the remaining 6 cases (4 laryngeal and 2 hypopharyngeal tumor) a superficial extending carcinoma was found to be associated with a deeply infiltrating squamous cell carcinoma of the "classic" type. Features useful to histopathologic diagnosis of superficial extending carcinoma and to its differentiation from preneoplastic and other neoplastic lesions of the laryngopharyngeal mucosa are emphasized. The possible association of superficial extending carcinoma with multiple synchronous and metachronous neoplastic lesions in the upper aerodigestive tract and the frequent underestimation of its real extension may have important clinical implications. PMID- 1437836 TI - Myxoid liposarcoma with t (12; 16)(q 13; p 11). Possible usefulness of chromosome analysis in a poorly differentiated sarcoma. AB - A chromosomal study was used to establish diagnosis of a poorly differentiated soft-tissue sarcoma occurring in the right thigh of a 57-year-old Japanese female. Histopathologically the excised tumor consisted of a poorly differentiated myxoid neoplasm, without specific features to enable the identification of neoplastic cells. Although a tentative diagnosis of poorly differentiated myxoid liposarcoma was made, ultrastructural examination and Oil Red O fat stain failed to demonstrate the evidence of lipoblastic differentiation, except that occasional cells possessed a small number of fine fat droplets. The diagnosis of liposarcoma was suggested by chromosome analysis of the fresh tumor tissue after short time culture and trypsin-Giemsa banding technique. The tumor cells demonstrated a clonal abnormality characterized by a reciprocal translocation, t(12; 16)(q 13; p 11), which is known as a specific aberration in myxoid liposarcoma. Thus, chromosome study seems to be useful for identifying undifferentiated mesenchymal tumors, which lack morphologic evidence of any specific differentiation, as in the present case. PMID- 1437837 TI - Relationship between quantity of silver stained nucleolar organizer regions associated proteins (Ag-NORs) and population doubling time in ten breast cancer cell lines. AB - Using a one-step silver staining technique ten human breast cancer cell lines were investigated, determining by means of automated image analysis the mean area of Ag-NORs per nucleus, the total number of Ag-NORs, and the so-called "scattered" and "clustered" Ag-NORs. These parameters were statistically correlated with the population doubling time (PDT) of the various carcinoma cell lines of this series. Our results show that the mean area of Ag-NORs per nucleus (p less than 0.001) is highly significantly correlated to the PDT, whereas all other parameters were less or not significant. It is concluded that the assessment of the area of Ag-NORs by automated image analysis is a simple and reliable method for the determination of cell duplication rates. PMID- 1437838 TI - Latent thyroid carcinoma in Iceland at autopsy. AB - The annual incidence rate of thyroid carcinoma in Iceland is high, 4.4 pr. 100,000 men, and 11.7 pr. 100,000 women, as published by the Icelandic Cancer Registry for the period 1955-1984. This rate is more than twice that in the other Nordic countries and one of the highest incidence rates reported anywhere. This led us to investigate the prevalence rate of latent thyroid carcinoma in Iceland. We serially sectioned and examined thyroid glands from 201 consecutive forensic autopsies. Altogether, sixteen carcinomas were identified in fourteen glands: fourteen papillary, one follicular and one medullary carcinoma. We conclude that the prevalence rate of latent thyroid carcinoma in each sex does not follow the frequency distribution of clinical disease, being 7.5% in males and 5.1% in females. Comparisons between populations show the same lack of consistency. Further, most, but not all, latent carcinomas of the thyroid gland are of the papillary type. These findings suggest that promoting factors might be of particular importance where incidence and mortality rates are high, but further research is needed into the role of host resistance. PMID- 1437839 TI - Cystic pancreatic glucagonoma in contact with insulinoma found in a hypoglycemic patient. AB - Cystic glucagonoma in contact with insulinoma was found in the pancreas of a 28 year-old female patient with characteristic hypoglycemic syndrome. Among six tumors in total detected in the tail of the resected pancreas, the largest solid tumor (2.5 cm in diameter) consisted mostly of insulin-containing cells with conspicuous amyloid deposition. Contiguous to this tumor, the second largest nodule, measuring 1.8 cm in diameter, showed cystic changes and consisted of glucagon-containing cells. High concentration of immunoreactive glucagon was demonstrated in the cystic fluid. In addition to the cystic changes of endocrine pancreatic tumors, simultaneous occurrence of glucagonoma in contact with insulinoma appears to be extremely rare and repeated episodes of hypoglycemia may contribute to its pathogenesis. PMID- 1437840 TI - Malignant schwannoma with rhabdomyoblastic and melanocytic differentiation. AB - This is the first case report of an unusual malignant tumor with components of malignant schwannoma, rhabdomyosarcoma, and melanoma, occurring in an adult. The tumor was observed in the left temple in a 35-year-old man without von Recklinghausen's disease. The possible derivation of this tumor from primitive neuroectodermal cells is discussed. PMID- 1437841 TI - "Medullary ray glomerular counting" as a method of assessment of human nephrogenesis. AB - Renal weight (left-right combined), as a parameter of renal development, is required to be less than half the normal value for age for a statistically confident diagnosis of hypoplasia. "Medullary ray glomerular counting" (MRGC), counting cortical glomerular generations, has been proposed as a simple technique of possibly greater sensitivity. Recent development of the Disector method for the unbiased stereological estimation of total glomerular number has provided a, hitherto unavailable, "golden standard" with which to determine the diagnostic potential of MRCG. Both "true" (actual number of generations seen) and "assumed" (a subjective "guess" of the total number of generations) MRGC counts were determined in 11 pairs of kidneys from spontaneously aborted, normally developed, non-malformed fetuses (gestational age: 15-40 weeks). Each kidney was randomly analysed blind and on two separate occasions by two paediatric pathologists using a written protocol. Results were compared with unbiased stereological estimates of glomerular number. Intra- and inter-observer and intra- and inter-(left right)renal reproducibility were analysed. In conclusion, MRGC, using "real" counts, is a highly reproducible parameter of renal development from 15-36 weeks' gestation. Sensitivity for detection of both hypoplasia and maturation delay increase with gestational age and generally exceeds that of renal weight. PMID- 1437842 TI - The conduction system in human cardiac allografts. A histological and immunopathological study. AB - Twenty-five hearts were lost in the first 103 orthotopic human cardiac allografts in 100 recipients. Twenty-two patients died. The first nine recipients were treated with Cyclosporin A and high dose Prednisolone and the subsequent recipients were immunosuppressed with a triple regimen consisting of Azathioprine in addition to Cyclosporin A and low dose Prednisolone. Twenty grafts were examined at autopsy and three after retransplantation. Fourteen hearts with acute rejection and vascular pathology were investigated regarding the histological and immunopathological alterations due to cellular and vascular rejection. The recipient sinoatrial node was available for examination in 10, the donor node in 13 and the atrioventricular conductive tissue in all 14 grafts. The conduction system was involved in 8 out of 11 allografts attacked by acute cellular rejection. In one allograft in which the patient developed AV block, the cellular infiltrates were almost exclusively observed in the atrioventricular tissue. Most of the cells were T lymphocytes, while macrophages and B cells were present to a lesser extent. There was little evidence of permanent structural damage to the atrioventricular tissue after recurrent mild or moderate episodes of acute cellular rejection. In the sinus nodes, however, risk of traumatic damage to the recipient and donor sinus node was about half and a quarter respectively. Acute and chronic vascular rejection seemed to be equally distributed in the sinus node, atrioventricular arteries and in the intramural branches of the coronaries. No morphological differences were established between the two types of immunosuppressive regimes. PMID- 1437843 TI - "Solid" variant of aneurysmal bone cyst. AB - A case of the so-called "solid" variant of aneurysmal bone cyst is reported. A 12 year-old girl with a few weeks' history of backache presented with a tender palpable mass located thoraco-spinal in the back at Th 3. Radiologically, the lesion was consistent with conventional aneurysmal bone cyst. Morphologically, it showed fibroblastic, fibrohistiocytic, fibromyxoid, osteoclastic and osteoblastic components as well as small aneurysmal sinusoids. Based on four other well documented cases, the clinico-pathological features and the differential diagnostical problems are discussed. PMID- 1437844 TI - "Lipoleiomyoma with metaplastic cartilage" (benign mesenchymoma) of the uterine cervix. AB - Benign mesenchymoma (BM) is an uncommon tumor containing two or more differentiated mesenchymal elements in addition to fibrous tissue. A case of BM of the uterine cervix in a 51-year-old woman is reported. This tumor, which we designated "lipoleiomyoma with metaplastic cartilage" because of its morphological features, apparently represents the first documented example of BM of the cervix. PMID- 1437845 TI - The genetic basis of multidrug resistance. AB - Cellular multidrug resistance, a common side-effect of anticancer chemotherapy frequently leading to failure of the treatment, has been characterized as an acquired resistance to several antimitotic drugs simultaneously. Multidrug resistance could mainly be attributed to the overexpression of the P-170 glycoprotein, considered as a drug-efflux pump encoded by the mdr 1 gene. Overexpression of this protein can be induced either by an accidental amplification or activation or both of the mdr 1 gene. Recent investigations focused on these mechanisms, aiming at a better understanding of the appearance of multidrug resistance during a chemotherapy. P-glycoprotein mediated drug resistance, however, is only one, albeit quite an important detoxification pathway, and some observations revealed genetic interactions with other systems. On the basis of this new knowledge, the development of novel therapeutic strategies to circumvent this clinical side-effect of cancer treatment has already begun. PMID- 1437846 TI - Sidero-elastosis pulmonum--M. Ceelen of the adult. PMID- 1437847 TI - Mycosis fungoides of erythematous stage. PMID- 1437848 TI - Aplastic crisis in haemolytic anaemia due to infection parvovirus B19. PMID- 1437849 TI - Professor Jerzy Gieldanowski, M.D. (1925-1991). PMID- 1437850 TI - On pharmacokinetic evaluation of model drugs distribution into rat central lymph. AB - Numerous experimental data obtained in the studies of factors influencing the transfer of model drugs (diazepam, inulin, hippurate) into the lymphatic system were evaluated using compartmental pharmacokinetic analysis. The selection of kinetic equations for lymphatic data analysis in respect to blood ones is specific. Lymphatic kinetic equations correspond in every case tested with those used generally in blood kinetic analysis of drugs administered perorally. The lag time parameter is useful in this lymphatic analysis, too. PMID- 1437851 TI - Reserpine ulcers in morphine dependent and withdrawal rats. AB - Reserpine ulcers were produced in dependent and withdrawal rats. The reactivity of isolated duodenum and colon to morphine and papaverine was tested in both groups of animals. Chronic administration of morphine decreases the development of post reserpine gastric ulcers, while in withdrawal rats it increases their occurrence. Relaxation and contraction responses of duodenum taken from the dependent rats showed tolerance. On the other hand, withdrawal rats displayed increased responses as compared with placebo group. Colon of dependent rats showed stronger responses to morphine and papaverine which indicates the lack of tolerance to morphine or enhanced receptors sensitivity. Stronger responses of colon in both dependent and withdrawal rats suggest the lack of tolerance in this segment of the gut. In withdrawal rats which obtained reserpine and placebo responses to papaverine were similar. It is suggested that reserpine decreased the sensitivity of mu receptor to morphine. PMID- 1437852 TI - Cytotoxic effect of xanthotoxol (8-hydroxypsoralen) on TCTC cells in vitro. AB - The effect of xanthotoxol (8-hydroxypsoralen) on proliferation of TCTC cells in vitro has been studied. Xanthotoxol at concentrations of 5 to 50 micrograms/ml inhibited the growth of cells. In cultures with xanthotoxol, decreased amount of cell protein, mitotic index, and decreased ability to form a colony, were observed. Moreover, xanthotoxol disturbed mitoses elevating the number of mitotic cells in the telophase stage. An increase of giant and multinuclear cells was also found. On the basis of these results it can be concluded, that 8 hydroxypsoralen which in comparison with other psoralens is not sensitive to photostimulation, inhibits the cell proliferation anyway. This fact shows that the mechanism of the psoralens activity is to some extent independent from the photostimulation. PMID- 1437854 TI - Amino acid concentrations in serum and urine after intravenous infusion of 1.5% glycine in prostatectomy patients. AB - Glycine 1.5% was given by intravenous infusion at a rate of 50 mg/min over 20 min to 10 patients (aged 57-79 years) scheduled for transurethral prostatectomy. The concentrations of amino acids in serum and urine were measured at 0, 10, 20, 50, 80, and 140 min in the experiments in order to study how elderly men handle a glycine load. The results show an increase in the serum concentrations of alanine, proline, glutamine, glycine, serine, and threonine. The apparent distribution volume for the excess glycine was 33 +/- 9 L, the half-life was 41 +/- 7 min, and the total body clearance was 0.56 +/- 0.08 L/min, while the renal clearance for glycine was 36 +/- 14 ml/min (mean +/- SD). There was an increase in the excretion of all amino acids that could be detected in the urine. The renal clearances of urea and creatinine was reduced in some of the patients. The absence of toxic symptoms is consistent with unchanged serum concentrations of ammonia and glutamate. PMID- 1437853 TI - Synthesis and some central pharmacological properties of new derivatives of 2,3 dihydroimidazo[1,2-a]pyrimidine-6-carboxylic acid. AB - Twenty one derivatives of 2,3-dihydroimidazo[1,2-a]pyrimidine-6-carboxylic acid (6 n-butyl amides and 15 free acids) bearing the aromatic ring in position 1 or 2 were obtained. They were synthesized by aminolysis or hydrolysis of respective ethyl esters. Pharmacological studies on the central action of eight compounds 1, 2, 4, 5, 7, 8, 9 and 10 were carried out on mice and rats. The most active compounds, producing sedation and hypothermia, and 1, 2 and 5. The compounds decreased amphetamine-induced hyperactivity. Besides, compound 2 exerted analgesic effect in mice. PMID- 1437855 TI - Estrogen-induced morphological and immunohistochemical changes in stroma and epithelium of rat ventral prostate. AB - Prostatic smooth muscle cells have been regarded to play a major pathogenetic role during the development of benign prostatic hyperplasia (BPH) in elderly men. Altered hormonal signals (increased estrogen) have been made responsible for the "metabolic" transformation of prostatic smooth muscle cells, which were thought to produce increased amounts of connective tissue fibers observed in BPH. In order to find out the role of metabolically "activated" smooth muscle cells, hormone stimulation experiments were performed in male rats. The effects of androgen deprivation and estrogen stimulation were recorded by semiquantitative analysis of intermediate and myofilament proteins in stromal smooth muscle cells. In castrated or estrogen-treated or estrogen-treated and castrated animals, the reduction of the glandular lumen is the most obvious morphological alteration, accompanied by an increase in connective tissue. Regressive changes occurred most rapidly in castrated animals (already within the first week), slower in castrated estrogen-treated animals and still slower in normal estrogen-treated animals. Regression of the epithelium was accompanied by a marked decrease in immunoreactivity for prostatic binding protein (PBP) in castrated animals, while PBP immunoreactivity in estrogenized animals was retained for up to 6 weeks. Smooth muscle cells became atrophic in castrated animals. This effect was attenuated in estrogen-treated animals. There was no indication for enhanced collagen synthesis by smooth muscle cells. Actin and desmin-immunoreactivity were only slightly altered in experimental animals and showed a changed distribution pattern. Prostatic smooth muscle cells respond less markedly to hormonal alterations than do the fibroblasts. PMID- 1437856 TI - The prostatic epithelial cell in dysplasia: an ultrastructural perspective. AB - The histologic features of prostatic duct-acinar dysplasia have been difficult to analyze ultrastructurally, because of the difficulty in properly selecting and processing such small, randomly situated grossly invisible lesions. We have succeeded in identifying dysplastic foci by examination of the cut surfaces of tissue slices under low magnification. Dysplasia foci were excised from the slices and were compared to adjacent normal tissue by both light and electron microscopy. By electron microscopy (EM), normal secretory cells were filled with myriad tiny clear vacuoles, which were markedly diminished to absent in the cytoplasm of dysplastic cells. Both apocrine and eccrine secretion characterized normal epithelium and were diminished in dysplasia. EM showed striking features of nuclear abnormality more prominently than light microscopy, and qualitative basement membrane abnormalities were revealed. By EM analysis, dysplastic epithelium resembled that of invasive carcinoma more than normal epithelial cells. PMID- 1437857 TI - Isolation and characterization of transforming growth factor beta response variants from human prostatic tumor cell lines. AB - In this study we examined the relation between the response to transforming growth factor beta (TGF beta 1) in vitro and the growth in vivo of 1-LN-PC3-1A (1 LN) human prostatic carcinoma cells. 1-LN cells resistant to the growth inhibitory effects of TGF beta 1 were isolated after exposure to 2 ng/ml TGF beta 1 in an anchorage-independent growth assay. Cloning of TGF beta 1-resistant and sensitive populations produced 2 clones (R2-6 and 1-LN clone 4), which maintained relatively stable resistance or sensitivity, respectively, in the absence of TGF beta 1 for up to 12 passages. Colony formation by the R2-6 cells in the presence of TGF beta 1 was 2-10 times greater than that of 1-LN clone 4, depending upon the TGF beta 1 concentration. Injection of 1 x 10(5) R2-6 cells into athymic nude mice produced tumors with a significantly shorter latency interval as compared with 1-LN clone 4 tumors (P < 0.0001). Western immunoblotting showed that higher levels of latent TGF beta 1 protein were secreted into the culture medium by 1-LN clone 4 cells. Acidified conditioned media from both clones inhibited mink lung epithelial cell DNA synthesis. Neutralizing monoclonal antibody to TGF beta 1 but not TGF beta 2 abrogated this inhibitory effect. Comparison of the different sensitive and resistant clones showed that in vitro sensitivity to TGF beta 1 and in vivo tumor latency interval were not invariably correlated. Thus, the TGF beta 1 response phenotype in vitro was not always predictive of growth delay in vivo. PMID- 1437858 TI - Dose-dependent induction of ornithine decarboxylase and S-adenosyl-methionine decarboxylase activity by testosterone in the accessory sex organs of male rats. AB - The dose-dependent induction of ornithine decarboxylase (ODC) and adenosylmethionine decarboxylase (AMDC) activity in the different lobes of the prostate and the seminal vesicles (SV), 24 hours after administration of testosterone to castrated Wistar rats, has been studied. ODC and AMDC activities were low in all lobes 10 days after castration. A dose of approximately 300 micrograms testosterone/100 g body weight (B.W.) gave an ODC activity of 50 percent of maximum response, and at 600 micrograms/100 g B.W. maximum activity was reached in all the prostatic lobes and the SV. In the lateral and dorsal prostate, and the coagulating gland, the dose of testosterone giving 50% of maximum AMDC activity was reached after administration of between 450 and 600 micrograms/100 g B.W. In the ventral prostate and SV, the dose giving a 50% response was approximately 700 micrograms/100 g B.W. In conclusion, all prostatic lobes showed a clear dose-response relationship concerning the activity of ODC and AMDC following administration of different doses of testosterone. We have found minor differences in androgen responsiveness between the lobes when looking at the dose requirements for induction of AMDC activity. The dose-response curves could possibly be useful as a rapid in vivo bioassay for compounds with anti androgenic properties in the prostate. PMID- 1437859 TI - The next 2 to 4 years in health care financing: a prediction. PMID- 1437860 TI - Both-bone forearm fractures in children. AB - Treatment of both-bone forearm fractures remains a difficult dilemma for the orthopedist. We assessed the results of 33 children treated with closed reduction and a long-arm cast using traction with finger traps in neutral rotation. Patients were grouped according to age and analyzed for residual angulation and range of motion (ROM). Despite some residual angulation and loss of rotation, all patients were fully active with no functional restriction at follow up. For patients 10 years old or younger with less than 30 degrees of post-casting angulation, full ROM and minimal residual angulation on radiograph can be expected. For patients ages 11 to 15 years (the oldest patient in this series was 15), residual angulation is likely and approximately 60% of patients will have residual loss of less than or equal to 30 degrees of rotation. In spite of this, we found no evidence of functional loss at follow up. Our series supports the continued use of closed manipulation as an effective treatment in children with both-bone forearm fractures. PMID- 1437861 TI - Evaluation of the degree of effectiveness of biobeam low level narrow band light on the treatment of skin ulcers and delayed postoperative wound healing. AB - Twenty-one patients with 31 postoperative delayed open wounds resistant to conventional therapy were randomly allocated to three groups. Group 1 was treated with red low level narrow band (LLNB) light (660 nm); group 2 was treated with infrared LLNB light (940 nm); and group 3 was treated with a placebo such as the Biobeam machine (no light irradiation). Group 1 showed a significant improvement compared to groups 2 and 3 (t-test). PMID- 1437862 TI - Energy demands for walking in dysvascular amputees as related to the level of amputation. AB - Cardiac function and oxygen consumption were measured in 25 patients who underwent amputation for peripheral vascular disease (PVD), and in five similarly aged control patients with PVD. Five patients at each of the midfoot, Syme's, below-, through-, and above-knee amputation levels and the five controls were measured at rest, normal walking speed, and maximum walking speed on a treadmill. At normal walking speed, all of the patients functioned at approximately 80% of their cardiac capacity. Normal walking speed and cadence decreased and oxygen consumption per meter walked increased with more proximal amputation. The ratio of cardiac function and oxygen consumption at normal walking speed as compared with at rest increased with more proximal amputation, and the capacity to increase walking speed and oxygen consumption lessened. Our results suggest that peripheral vascular insufficiency amputees function at a level approaching their maximum functional capacity. At more proximal amputation levels, the capacity to walk short or long distances is greatly impaired. PMID- 1437863 TI - Current method of treatment of acromioclavicular joint dislocations. PMID- 1437864 TI - Cumulative trauma disorders. AB - Cumulative trauma disorders have increased five-fold since 1979 and now account for up to 47% of workplace injuries. Nerve entrapment, tendonitis, and other soft tissue injuries are the most common diagnostic groups. Both occupational and non occupational factors contribute to the etiology of these disorders. Epidemiology, differential diagnosis, and interventions for treatment are reviewed. PMID- 1437865 TI - The "genuflex" skin closure for total knee arthroplasty. PMID- 1437866 TI - Lateral compartment arthritis of the knee accelerated by medial displacement osteotomy of hip fractures. PMID- 1437867 TI - Cryptococcus neoformans osteomyelitis of the clavicle. PMID- 1437868 TI - Legg-Calve-Perthes disease and slipping of the capital femoral epiphysis in the same child. PMID- 1437869 TI - A helpful radiographic sign in CDH. PMID- 1437870 TI - Quadricepsplasty: the Judet technique and results of 21 posttraumatic cases. AB - Twenty-one quadricepsplasty procedures were carried out on 21 patients over a 14 year period due to posttraumatic stiffness of the knee joint. Three patients (14.2%) required mobilization under anesthesia in the early postoperative period. The average interval between injury and quadricepsplasty was 18 months (range: 5 to 49 months). Preoperatively, all cases showed less than 90 degrees knee flexion. At follow up, 12 cases (57.2%) achieved more than 90 degrees flexion, while nine patients (42.8%) exhibited under 90 degrees flexion. Flexion gain was between 60 degrees and 90 degrees in six cases (28.5%) and less than 60 degrees in 15 cases (71.5%). Results were assessed according to Judet et al. There were 14 excellent and good (66.6%) and seven fair (33.3%) results. No poor results were found in this series. PMID- 1437871 TI - Rehabilitative techniques in the treatment of medial and lateral epicondylitis. PMID- 1437872 TI - Open anterior acromioplasty vs arthroscopic anterior acromioplasty. PMID- 1437873 TI - Tibial tuberosity fracture associated with a compartment syndrome. PMID- 1437874 TI - Answer please. Femoral head and acetabulum fractures associated with a posterior hip dislocation--Pipken 4. PMID- 1437875 TI - The value of a case report--a case study. PMID- 1437876 TI - Dermatoglyphics in sudden infant death syndrome. AB - An analysis of digital and palmar dermatoglyphic patterns was conducted in 173 victims of the sudden infant death syndrome (SIDS). The results expose four dermatoglyphic regions with pattern frequencies differing from those in a control population. These are an excess of Sydney creases, hypothenar patterns, open fields (with fewer vestiges) in interdigital region IV, and arches on all digits (females only). These findings indicate a genetic or early intrauterine environmental influence in SIDS infants. An increased incidence of dysmorphism and anomalies including recognition of specific syndromes support this contention. One could speculate that these dermatoglyphic deviations reflect specific genotypes and/or phenotypes particularly vulnerable to postnatal challenges. Differences in multiple dermatoglyphic categories support the concept of heterogeneity of the SIDS population and multicausality of SIDS. PMID- 1437877 TI - Morphometric study on pulmonary arterial thickness in pulmonary hypoplasia. AB - This study addresses the question of whether pulmonary hypoplasia is associated with structural changes of the pulmonary arteries. Quantitative (medial thickness, external radius) and qualitative (airway level) parameters of pulmonary arteries were assessed in eight hypoplastic lungs and eight lungs from age-matched fetuses without underlying primary pulmonary disease. The gestational ages ranged from 16 to 40 weeks. Relative medial thickness of the pulmonary arteries was related to the external radius and to the type of accompanying airway. Medial thickness was significantly higher in pulmonary hypoplasia than in normal fetal lungs. In contrast to normal fetal lungs, muscular arteries extended to the intra-acinar level in pulmonary hypoplasia. These arteries had medial thickness values up to a maximum of 80%. PMID- 1437878 TI - Fetal listeriosis during the second trimester of gestation. AB - Listeriosis is common and is implicated in about 3% of second-term abortions examined in our laboratory. Maternal fever was followed rapidly in all instances by the expulsion of a nonmacerated fetus. Chorioamnionitis was always present and was associated with placental microabscesses. Leukocytic infiltrates were frequent in fetal tissues, being present in adrenal, lung, and skin. Listeria monocytogenes was isolated from 8 of the 205 abortions that had microbiological cultures (3.9%). The clinical features and morphological lesions were so characteristic that the diagnosis of listeriosis could be made in 5 of the 217 fixed abortuses received during the same period, but without culture. In contrast to the third trimester of pregnancy, there were no inflammatory lesions in the central nervous system in our small series. PMID- 1437879 TI - Association of Down syndrome and segmental tracheal stenosis with ring tracheal cartilages: a review of nine cases. AB - Four patients with Down syndrome and midtracheal stenosis, three with proven absence of the midtracheal pars membranacea ("hourglass trachea"), are reported. Five previously reported patients who had Down syndrome and tracheal stenosis of this type are summarized. Respiratory difficulty and stridor were the reported clinical features of all but one of the patients whose clinical story is available. That approximately half the patients with tracheal stenosis with hourglass trachea and midtracheal absence of the tracheal pars membranacea reported had Down syndrome suggests that the association of this pattern of congenital tracheal stenosis with Down syndrome is, although infrequent, significant. PMID- 1437880 TI - Juxtagonadal mesonephric glomeruli in fetuses of 11 to 21 weeks of gestation. AB - Mesonephric glomeruli and tubules were found in the juxtagonadal region in 11 fetuses ranging in age from 11 to 21 postmenstrual weeks. Although mesonephric excretory function into the fourth month of gestation has been postulated, mesonephric glomeruli have been previously acknowledged anatomically only during embryonal and early fetal life. The present observations indicate that mesonephric glomeruli persist as anatomical structures into the midtrimester of gestation. The conclusion that the observed glomeruli are mesonephric is based on their location and the known strong anatomical and functional ties that bind mesonephros and gonad during development. PMID- 1437881 TI - Poorly organized parasitic conjoined twins: report of four cases. AB - We report four examples of parasitic conjoined twins (PCT) that created difficulties in diagnosis and treatment because of their unusual presentation and poor internal organization. Case 1 appeared as a tumor on the back containing an adrenal gland and part of the small bowel and stomach; two spines with spinal cords were present. Case 2 was similar, but mature and immature renal tissue were included and a meningocele with Arnold-Chiari type II malformation was recognized in the autosite spine. Retrospective interpretation of both cases suggested that the left lower limb and pelvis were part of the parasites. In case 3 the parasite was attached at the perineum and lower abdomen, contained a rudimentary spine in continuity with the coccyx of the autosite, and was partially covered by scalp. Case 4 presented as a limblike tumor attached at the suprapubic region. All cases were complicated by disruptions in the autosites. Surgical treatment was successful in cases 1, 2, and 3. These four anatomically poorly organized PCT are best categorized as intermediate between teratomas and the more common types of PCT. PMID- 1437882 TI - Web-like malformation of the carotid artery and multicystic encephalomalacia. AB - Multicystic encephalomalacia and hydranencephaly lie within a spectrum of brain lesions linked to ischemic cerebral damage. Causes include vascular malformation, thrombosis, embolism, infection, and toxins. We describe an infant with multicystic encephalomalacia associated with a peculiar web-like malformation of the right common carotid and left subclavian arteries. We postulate that this luminal bridging is a congenital malformation resulting from defective canalization of the medium-sized blood vessels but could represent organized and recanalized thrombi, the etiology of which remains unknown. PMID- 1437883 TI - Perinatally acquired neonatal tuberculosis: report of two cases. AB - Perinatally acquired neonatal tuberculosis occurs rarely, is difficult to diagnose, may be the indicator of untreated tuberculosis in the mother, and could result in nosocomial transmission to neonatal patients, visitors to neonatal intensive care units, and health care workers. The disease may be more common in certain ethnic and social groups. Neonatal mortality approaches 30%. We report two cases with different outcomes. A neonate was treated for clinical miliary tuberculosis and survived; Mycobacterium tuberculosis was cultured from bronchoscopic washings, maternal genital fluids, and tissues. A second infant died at age 46 days, and autopsy disclosed miliary tuberculosis of lungs, mediastinal and mesenteric nodes, liver, spleen, and bone marrow. The lungs were most severely affected, but the placenta and central nervous system were not involved. The histopathology was not granulomatous. After the diagnosis in the infant, the mother was ascertained to have pulmonary and genital tuberculosis. Fetal and neonatal tuberculosis could be acquired transplacentally as prenatal tuberculous chorioamnionitis, perinatally through aspiration and ingestion of infected maternal genital tissues and fluid, or postnatally through droplet spread from cases of active tuberculosis. These two neonates probably acquired the disease perinatally from maternal genital tuberculosis. PMID- 1437884 TI - Maxillo-mandibular development in cerebrocostomandibular syndrome. AB - Cerebrocostomandibular syndrome is a potentially lethal developmental disorder characterized by mental handicap, palatal defects, micrognathia, and severe costovertebral defects. We report a 3-day-old male neonate who died of respiratory difficulty that began at birth. Micrognathia, glossoptosis, high arched palate, and hypoplasia of the lower half of the face were present. Multiple posterior rib defects and a narrow rib cage were associated with pulmonary hypoplasia. The rib gaps were filled with fibrovascular tissue. A facial bone study showed multifocal growth retardation involving the septal cartilage, vomer, and mandibular condyle, indicative of maxillomandibular growth arrest. The tongue had an abnormal genioglossus muscle and papillae. PMID- 1437885 TI - Pigmented villonodular synovitis in the sacral joint with extensive bone destruction in a child. AB - We report a 12-year-old girl who had pigmented villonodular synovitis with extensive bony erosion around the left sacroiliac joint. The lesion mimicked a primary bone tumor clinically and radiologically, but was a typical pigmented villonodular synovitis (PVNS). The sacroiliac joint is an unusual site for PVNS, especially in the pediatric age group. PMID- 1437886 TI - Rhabdomyomatous mesenchymal hamartoma of skin. AB - A distinctive dermal and subcutaneous hamartoma composed primarily of disorganized skeletal muscle and mature adipose tissue, designated rhabdomyomatous mesenchymal hamartoma of skin, was recently reported. We have observed two histologically similar though less polypoid lesions in boys aged 4 years. Both were also on the chin and present since birth, suggesting that site and age, as well as histology, may be characteristic. The location on the chin in three of the four neonates may reflect an etiology of aberrant embryologic development of the platysma muscle as it inserts superficially into the dermis over the mandible. PMID- 1437887 TI - Reactive follicular hyperplasia of intraparotid lymphoid tissue presenting as a recurrent parotid enlargement. AB - A patient who had reactive lymphoid hyperplasia of intraparotid lymphoid tissue, clinically presenting as a recurrent parotitis, is described. The case offers a new etiologic mechanism for recurrent parotitis. PMID- 1437888 TI - Axonal dystrophy presenting as the megacystis-microcolon-intestinal hypoperistalsis syndrome. AB - Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) is a neonatal intestinal syndrome, characterized by defective peristalsis and bladder dilatation, refractory to pharmacological treatment. Examinations of bowel and bladder have failed to demonstrate a pathological explanation for this syndrome. We describe a 7-month-old female infant with MMIHS who had generalized axonal dystrophy of her central, peripheral, and autonomic nervous systems, which may provide a neuropathological explanation for some cases of MMIHS. PMID- 1437889 TI - Sudden death in supravalvular aortic stenosis: fusion of a coronary leaflet to the sinus ridge, dysplasia and stenosis of aortic and pulmonic valves. AB - Supravalvular aortic stenosis (SVAS) is an uncommon congenital cardiac anomaly. We report sudden death, occurring during exercise, of a child who had SVAS with fusion of the right coronary aortic leaflet to the supravalvular aortic ridge, resulting in a closed sinus of Valsalva except for a few pinpoint fenestrations in the dysplastic leaflet. In addition, both aortic and pulmonic valves were dysplastic and stenotic. We postulate that near total isolation of the right coronary artery ostium from the aortic lumen compromised the blood supply to the hypertrophied ventricles. We emphasize the importance of other cardiac anomalies associated with SVAS as well as the development of coronary insufficiency. PMID- 1437890 TI - Massive perinatal hepatic necrosis from maternal oxytocin overdose. AB - Review of clinical records regarding administration of oxytocin may provide clues to the etiology of hepatic infarction in the neonate. The authors present a case in which a large and rapid maternal overdose of oxytocin (17,300 mU over 20 min) during end-stage labor was associated with neonatal death and extensive hepatic infarction. These findings represent novel complications of oxytocin administration. PMID- 1437891 TI - Case 1. Acute torsion of the testis. PMID- 1437892 TI - Case 2. Carbon monoxide poisoning. PMID- 1437893 TI - Diagnosis in pediatrics. PMID- 1437894 TI - Decision making and the child with febrile seizures. PMID- 1437895 TI - Decision making and the child with afebrile seizures. PMID- 1437896 TI - Behavior and allergy: myth or reality? PMID- 1437897 TI - The pediatrician's role in the diagnosis and treatment of substance abuse. AB - Abuse of drugs and alcohol is pervasive in our society. The role of the pediatrician as a health-care provider from birth through young adulthood includes recognizing the stigmata in newborns of prenatally ingested drugs as well as being able to treat neonatal drug withdrawal syndromes. Questioning about drug use and other closely related topics should be incorporated into all health care maintenance visits, starting at the age of 10 y, with parental participation and anticipatory guidance being offered. Physical examination and laboratory testing are not as helpful in confirming an impression of substance abuse as a comprehensive interview and a full appreciation of the warning signs of substance abuse. Treatment of the problematic user with a multidisciplinary team that understands adolescent development and behavior as well as the problem of substance abuse is crucial. The decision to treat the teen in an ambulatory or inpatient setting is determined by the extent of abuse, underlying medical problems and psychopathology, and the degree of family dysfunction. The pediatrician must not avoid addressing these issues with patients. If, however, upon identifying an adolescent or a newborn with a drug problem, the pediatrician feels uncomfortable or ill-prepared to manage the patient, appropriate professional referrals are warranted. Despite exercising the referral option for treatment, as advocate for child and family, the pediatrician remains professionally bound to track all drug abuse-related referrals while continuing to participate in the general ongoing care of the patient and family. Finally, the pediatrician should retain a public advocacy role in the community by offering educational, preventive, and supportive efforts in the continuing struggle against drug abuse. PMID- 1437898 TI - Acute and chronic immune thrombocytopenic purpura. Disorders that differ in more than duration. AB - Immune thrombocytopenic purpura is a relatively common disease that occurs in both pediatric and adult populations. The acute form predominates in children and the chronic form is seen much more often in adults. The diagnosis is one of exclusion but often can be made on the basis of thorough history taking and physical examination and a limited number of laboratory studies. More intensive diagnostic studies, including bone marrow examination, may be needed to rule out other causes of thrombocytopenia. For patients in whom spontaneous remission does not occur, effective treatments are available, and morbidity and mortality rates are quite low. PMID- 1437899 TI - Control of type II diabetes. Reaping the rewards of exercise and weight loss. AB - After a complete physical examination to identify possible complications, patients with non-insulin-dependent (type II) diabetes mellitus should be placed on an exercise program and a weight-control diet. Individualizing these regimens according to patients' health goals and personal interests enhances the chance of success. Exercise guidelines must be followed to ensure the patient's safety. Weight loss, however moderate, should be encouraged, and once a reasonable weight is obtained, a balanced maintenance diet should be recommended. Patience and persistence by physicians and patients can bring success in management of type II diabetes with nonpharmacologic means. PMID- 1437900 TI - Hats and beds. Ralph Nader thinks 'it's already working'. PMID- 1437901 TI - Vocal cord dysfunction mimicking bronchial asthma. AB - Vocal cord dysfunction is a possible cause of wheezing and dyspnea in patients who do not respond to conventional asthma therapy. A carefully taken history, pulmonary function testing, and, most important, direct visualization with a flexible laryngoscope during an acute attack allow physicians to differentiate vocal cord dysfunction from asthma. Speech therapy, inhalation of helium and oxygen, and psychiatric counseling play a role in management. PMID- 1437902 TI - Acute urinary tract infection in women. What kind of antibiotic therapy is optimal? AB - Urinary tract infections continue to be a major health problem for women. Understanding of the pathogenesis of urinary tract infections has improved; Staphylococcus saprophyticus has been recognized as a common causative agent, and low-colony-count infections are misdiagnosed less often. Traditional therapy with 10 days of amoxicillin (Amoxil, Wymox) or ampicillin (Omnipen, Totacillin) is no longer considered optimal. For women who fulfill certain clinical criteria, short course therapy is recommended--preferably 3 days of trimethoprim sulfamethoxazole, or trimethoprim alone (Proloprim, Trimpex) if the woman is allergic to sulfonamides. Longer therapy is indicated for women with complicated, prolonged, or recurrent infections. To appropriately treat patients and avoid overtreatment that would increase both costs and the incidence of side effects, physicians need to stay abreast of information about pathogens, mechanisms of disease, new drugs, and common resistance patterns. PMID- 1437904 TI - In Indian country. PMID- 1437903 TI - Retinoid therapy for aging skin and acne. AB - Primary care physicians should be familiar with the effects and appropriate uses of retinoids. Topical tretinoin (Retin-A) can reverse photoaging of the skin, although some transient, undesirable side effects usually occur. In patients with acne vulgaris, topical tretinoin and systemic isotretinoin (Accutane) are the only agents that act upon the apparent underlying causes. Recurrence is unlikely after successful results are achieved. Chronic hypervitaminosis A presents insidiously, and physicians must maintain a high index of suspicion. Complete history taking should always include questions about the patient's use of vitamin supplements. PMID- 1437905 TI - The wrong side of the bed. PMID- 1437907 TI - Medical care in France. PMID- 1437906 TI - Predicting outcome after brain injury. PMID- 1437908 TI - Polyps in the colon. Answers to key questions. AB - Adenomatous polyps in the adult colon and rectum are of great clinical importance because they can undergo malignant degeneration. Size and histologic type are useful in predicting the likelihood of malignancy. In most cases, biopsy is required to distinguish small adenomas (< 1 cm) from hyperplastic polyps, which do not undergo malignant degeneration. An adenomatous polyp found during proctosigmoidoscopy warrants total colonoscopy with polypectomy, because of the possibility of a synchronous adenoma or cancer. Periodic colonoscopic follow-up is advised, because of the high rate of recurrent ("metachronous") adenomas. The optimal screening technique for colorectal polyps and early cancer in the general population remains to be defined. The most commonly used program at present entails periodic fecal occult blood testing and flexible proctosigmoidoscopy. Diets high in fiber and low in fat may have protective effects against the development of colonic neoplasms. PMID- 1437909 TI - Nuclear myocardial perfusion imaging in acute myocardial infarction. Which technique is best? AB - Although diagnosis of acute myocardial infarction is usually based on the patient history and electrocardiographic findings, nuclear myocardial perfusion imaging has an important role in assessing myocardial damage and predicting patient prognosis. In this article, Dr Umfrid discusses the unique characteristics of technetium Tc 99m sestamibi that make it especially useful in managing acute myocardial infarction. PMID- 1437910 TI - Dysphagia. A practical approach to diagnosis. AB - Our diagnostic approach to a patient with dysphagia begins with detailed history taking and physical examination. On the basis of findings, a radiographic and/or endoscopic study of the esophagus is done. We usually have barium-swallow radiography done initially, and if the radiographs are equivocal, upper gastrointestinal endoscopy is performed. Manometric studies are reserved for patients with suspected motility disorders. PMID- 1437911 TI - Sideroblastic anemia. A diagnosis to consider in alcoholic patients. AB - Alcoholic patients who present with anemia can pose a diagnostic challenge. Although deficiencies of iron, vitamin B12, and folate commonly result in anemia, bone marrow suppression of red blood cell production related to the direct toxic effects of alcohol can cause a form called sideroblastic anemia. This case report describes a patient presenting with acute alcohol intoxication and anemia in whom extensive evaluation revealed a hematologic picture compatible with acquired sideroblastic anemia. PMID- 1437912 TI - OSHA breaks a rule. PMID- 1437913 TI - Benefits and risks of oral contraceptive use. AB - As a general rule, the lowest-dose oral contraceptive should be prescribed that minimizes side effects while maintaining contraceptive protection. A woman who experiences mild side effects should be encouraged to tolerate symptoms for three menstrual cycles before a decision is made to change the prescription. Compliance may also be improved by informing women of the noncontraceptive health benefits of oral contraceptives: less menstrual blood loss and a lower incidence of menorrhagia, irregular bleeding, benign breast disease, endometrial cancer, dysmenorrhea, ovarian cysts or tumors, and salpingitis. Adequate patient education and supportive counseling are key factors in patient satisfaction and hence compliance. PMID- 1437914 TI - OSHA's 'phantom accuser'. PMID- 1437915 TI - Tetanus. A threat to elderly patients. AB - Tetanus rarely occurs in young persons now that childhood immunization programs are widespread. Many older patients, however, are not completely immunized, and mortality in this group is high. Since many of the wounds from which tetanus arises are minor, patients may not bring them to medical attention. Thus, physicians should include assessment of immunization status during routine office visits in all age-groups and provide immunization against tetanus and against diphtheria if indicated. PMID- 1437916 TI - HIV infection in athletes. What are the risks? Who can compete? AB - The activities of athletes and personnel who provide their medical care may place them at slightly greater risk for infection with human immunodeficiency virus (HIV) than their nonathletic peers. At this point, there is no reason to disallow participation of athletes who are HIV-infected. Thus, sports physicians need to assume that they are at risk for accidental exposure to HIV and use appropriate precautions. Most important, physicians can educate athletes, coaches, and trainers to practice "safe" athletics and medical care to minimize the risks of exposure to and transmission of HIV. Testing for HIV can be encouraged for athletes who may be at risk and should be done for any athlete who specifically requests it. Physicians should encourage further study to clarify the specific issues and risks of HIV infection created by athletic competition and prepare to deal with the changing knowledge about HIV and AIDS. PMID- 1437917 TI - Cardiac enzymes. How to use serial determinations to confirm acute myocardial infarction. AB - Although acute myocardial infarction can be diagnosed on the basis of clinical history, electrocardiographic (ECG) findings, and abnormalities of creatine kinase (CK) and lactate dehydrogenase (LDH) enzyme levels, measurement of cardiac enzyme levels is the most reliable way to confirm or exclude the diagnosis. If the MB isoenzyme of creatine kinase (CK-MB) remains normal during the 48 hours after the suspected clinical event, acute myocardial infarction can be reliably ruled out; if CK-MB values become elevated and the LDH isoenzyme pattern (LDH2:LDH1 ratio) becomes "flipped," the diagnosis can reliably be made. However, if CK-MB values become elevated but the LDH isoenzyme pattern remains normal, the diagnosis is less firm and ECG and myocardial imaging techniques may be needed to confirm or exclude myocardial infarction. PMID- 1437918 TI - Echocardiography. Using its many capabilities to evaluate myocardial infarction. AB - How can the suspicion of myocardial ischemia be confirmed without putting the patient through an invasive procedure? In patients who have had myocardial infarction, how can those at risk for pump failure and other complications and future cardiac events be identified? How are such complications detected? The answer to all these questions is echocardiography. The authors review how to use the technique and provide illustrative images. PMID- 1437919 TI - Treatment options for colorectal liver metastases. PMID- 1437920 TI - Diagnosis and management of ventricular tachycardia. PMID- 1437921 TI - Infectious diseases and AIDS. PMID- 1437922 TI - Infusion rate and pharmacokinetics of intravenous pamidronate in the treatment of tumour-induced hypercalcaemia. AB - We report the results of two consecutive randomized studies in the treatment of malignant hypercalcaemia with intravenous pamidronate. Overall normocalcaemia was achieved in greater than 90% of patients and a single infusion of 60 mg pamidronate given over 2 hours was as effective in restoring normocalcaemia as infusions given over 4, 8 or 24 hours. Similarly duration of normocalcemia after treatment with pamidronate and the control of the symptoms of hypercalcaemia were independent of infusion rate. Study of the pharmacokinetics of pamidronate in the treatment of hypercalcaemia show this drug to have a very high clearance due to calcified tissue retention and renal excretion. The initial half life of the drug in plasma is very short and most of the drug is cleared before distribution equilibrium is achieved. Short infusions of pamidronate are as safe and effective as infusions given over a longer time and are therefore to be preferred because of their greater convenience. PMID- 1437923 TI - Systemic lupus erythematosus in 50 year olds. AB - We compared the clinical and serological characteristics of 15 patients with onset of systemic lupus erythematosus after the age of 50 with those of 232 younger patients. The sex distribution was similar in both groups. All 15 patients were Caucasian. Autoimmune thyroiditis was found in 20% of the elderly patients. Initial manifestations, which presented more frequently in the older group, included thrombocytopenia (P < 0.05), sicca syndrome (P < 0.01) and cardiomyopathy (P < 0.005), whereas butterfly rash (P < 0.05) presented more frequently in the younger group. Analysis of cumulative clinical symptoms showed that butterfly rash (P < 0.05) and livedo reticularis (P < 0.05) were less frequent in the elderly. However, this group presented a significantly increased incidence of sicca syndrome (P < 0.005) and cardiomyopathy (P < 0.005). Antibodies to double-stranded DNA tended to occur less frequently in older patients (P < 0.05). PMID- 1437924 TI - The late presentation of postero-lateral congenital diaphragmatic hernias. AB - Four patients presenting after the neonatal period with a combination of respiratory and gastro-intestinal symptoms and signs which point to the diagnosis of congenital postero-lateral diaphragmatic hernias are discussed. Late presentation is more common than previously acknowledged. Early correct diagnosis and treatment are associated with an excellent clinical outcome. PMID- 1437925 TI - Intussusception in the adult: clinical, radiological and histological features. AB - Intussusception in the adult is an unusual cause of bowel obstruction. Unlike in childhood the clinical presentation is not clear cut and there are no distinct pathognomonic features. The radiological features are variable. Five patients presented to Frenchay Hospital over a five month period. The patients' clinical courses demonstrate the differing presenting features. Ultrasound investigation and CT scanning may show characteristic signs. Surgical treatment is mandatory as there is nearly always an underlying pathological abnormality which may be malignant. PMID- 1437926 TI - The role of faecal Candida albicans in the pathogenesis of food-intolerant irritable bowel syndrome. AB - Candida albicans was sought in stool samples from 38 patients with irritable bowel syndrome and 20 healthy controls. In only three patients with irritable bowel syndrome was C. albicans discovered and these patients had either recently received antibiotics or the stool sample had been delayed more than 24 hours in transit. C. albicans was isolated from none of the control stool samples. We conclude that C. albicans is not involved in the aetiology of the irritable bowel syndrome. PMID- 1437927 TI - Lipomatosis of the ileocaecal valve simulating Crohn's disease. PMID- 1437928 TI - Endoscopic therapy for bile duct stones in a geriatric population. AB - During the 5 year period to May 1988, 137 consecutive patients (age range, 65-102 years; median 84 years) with a diagnosis of choledocholithiasis, were referred to The Middlesex Hospital Geriatric Department. Endoscopic sphincterotomy was successful in 96.2% of cases and immediate biliary drainage was achieved in all but one of these patients. Stones were cleared endoscopically in 73.3% and surgically in 4.7% of cases. Long-term stenting was employed in 14.3% of patients. The 30 day mortality after endoscopic or surgical treatment was 4.7% (six deaths), although death was probably unrelated to therapy in half the cases. Deaths were due to procedural cardiorespiratory arrest (1), pancreatitis (1), pneumonia (2) and cerebrovascular accident (2). Endoscopic treatment is effective even in a high-risk geriatric population. After sphincterotomy patients with intact gall bladders should be managed expectantly. PMID- 1437929 TI - Tumours of the accessory lobe of the parotid gland. AB - Three cases of tumour of the accessory lobe of the parotid gland are reported and the surgical aspects discussed. An approach through a routine parotidectomy incision is preferred to direct incision over the mass. PMID- 1437930 TI - Carotid sinus syndrome after carotid artery surgery. AB - A 63 year old woman had been intensively treated for recurrent carcinoma of the neck. Following acute vascular surgery of the carotid artery, she developed the vasodilatory type of the carotid sinus syndrome. The presentation of this type of the syndrome was remarkable, since it is usually associated with primary or metastatic carcinoma in the neck region. Previous cancer treatment may have modified the course of disease in this patient, which ultimately had a lethal outcome. PMID- 1437931 TI - Addisonian crisis presenting with a normal short tetracosactrin stimulation test. AB - We report the case of a 70 year old man who presented with physical and biochemical features suggestive of Addison's disease, but had a normal short tetracosactrin (Synacthen) test. Six months later he re-presented with similar clinical features but with an abnormal response to tetracosactrin confirming the diagnosis of Addison's disease. We recommend that if adrenal insufficiency is strongly suggested further investigation should be performed to exclude this diagnosis. PMID- 1437932 TI - Suprasellar ectopic pituitary adenoma presenting as cranial diabetes insipidus. AB - We describe the occurrence of a supracellar ectopic pituitary adenoma in a 34 year old woman who presented with cranial diabetes insipidus and subsequently developed galactorrhoea-amenorrhoea. The tumour was demonstrated by both contrast computed tomography scan and magnetic resonance imaging with gadolinium enhancement and was confirmed at operation. Histological examination showed that the suprasellar lesion consisted of a pituitary adenoma while the pituitary biopsy revealed an unrelated pituitary microadenoma embedded in normal pituitary tissues. A review is made of the reported cases of ectopic pituitary adenomas. PMID- 1437933 TI - Non-secretory multiple myeloma presenting as primary plasma cell leukaemia. AB - A case of non-secretory multiple myeloma presenting as primary plasma cell leukaemia in a 65 year old woman is presented. Bone pain was the initial clinical manifestation. Laboratory analysis showed 20% of circulating immature plasma cells. Despite the presence of osteolytic lesions, no M-component could be demonstrated in serum protein electrophoresis, and serum and urine immunoelectrophoresis. Bone marrow aspirate demonstrated an 83% infiltration of plasma cells showing various degrees of immaturity. Immunofluorescence with monoclonal antisera demonstrated intracytoplasmic kappa light chains in a high percentage of plasma cells. Immature plasma cells without cellular capacity to synthesize and excrete complete immunoglobulins could be more aggressive, leading to an initial leukaemic process. Previous work regarding possible pathogenetic mechanisms, clinical and laboratory features, and response to treatment of this extremely rare association are reviewed. PMID- 1437934 TI - A late complication of pectus excavatum repair. AB - We report a late complication of pectus excavatum repair which highlights the importance of a chest X-ray in evaluating chest pain in patients who have had previous chest surgery. It also raises the question of whether or not implanted wires should be electively removed following bony union. PMID- 1437935 TI - Sub-clinical systemic lupus erythematosus presenting with acute myocarditis. AB - A 46 year old woman presented with fever and normochromic anaemia followed rapidly by severe myocardial failure, unresponsive to maximum inotropic support and broad spectrum antibiotics. There were no classical clinical stigmata of systemic lupus erythematosus (SLE) but a possible immunological cause was looked for, and on the basis of her immuno-serology a diagnosis of SLE-like disease was made. She responded rapidly to high dose steroids. The importance of considering the possibility of SLE or 'lupus overlap' in an acutely ill 'undiagnosed' patient is emphasized. The relevance of instigating appropriate immuno-serological tests in the course of such an illness is discussed. PMID- 1437936 TI - Acute intermittent porphyria treated by testosterone implant. AB - The hereditary disorder acute intermittent porphyria is potentially fatal. Many more females present with active disease than males and some have attacks related to their menstrual cycle and pregnancy. We present a female patient who was diagnosed while pregnant at 19 years. She subsequently developed life-threatening attacks pre-menstrually at 24 years; these were associated with weight loss. Initial treatment was with high calorie feeding via a naso-gastric tube, followed by a gastrostomy. Subsequent gonadotrophin suppression with intranasal luteinizing hormone-releasing hormone analogue (buserelin) thrice daily met with limited success. We implanted 100 mg of testosterone subcutaneously in November 1989. The buserelin was discontinued in January 1990 and menses returned 3 months later. There have been no serious attacks since then. Repeat implantation was performed at 6 monthly intervals until her present pregnancy. Baseline biochemical parameters have remained high and unaltered despite treatment although the testosterone has clearly had a marked clinical benefit, without side effects. PMID- 1437937 TI - Thyroid register audit: a district general hospital experience. PMID- 1437938 TI - Cauda equina syndrome associated with ankylosing spondylitis in a female. PMID- 1437939 TI - Worsening neurological status in late pregnancy: consider meningioma. PMID- 1437940 TI - Carcinoma of the splenic flexure--a case for extended right hemicolectomy? PMID- 1437942 TI - Festschrift for Lord Walton of Detchant. PMID- 1437941 TI - Intracranial tuberculoma: paradoxical expansion during medical treatment. PMID- 1437943 TI - Lord Walton of Detchant. PMID- 1437944 TI - The muscular dystrophies. PMID- 1437945 TI - Reviewing multiple sclerosis. PMID- 1437946 TI - Cluster headache and its variants. PMID- 1437947 TI - Epilepsy. PMID- 1437948 TI - Alzheimer's disease. PMID- 1437949 TI - Motor neuron disease. PMID- 1437950 TI - Parkinson's disease. PMID- 1437951 TI - The role of the speech and language therapist in the assessment and management of dysphagia in neurologically impaired patients. PMID- 1437952 TI - Eradication of Helicobacter pylori: therapies and clinical implications. AB - This review presents a critical evaluation of the role of Helicobacter pylori eradication in the management of peptic ulcer disease and non-ulcer dyspepsia. On current evidence, H. pylori eradication therapy seems likely to emerge as the most rational and cost-effective treatment for duodenal ulcer. The role of H. pylori eradication in the treatment of gastric ulcer and non-ulcer dyspepsia is unclear and requires further study. The emerging problem of antibiotic resistance in H. pylori is of major clinical importance and a prime cause of treatment failure. There is increasing evidence of a link between H. pylori and gastric cancer but it is premature to recommend large-scale eradication of H. pylori as a valid strategy for the primary prevention of gastric cancer. The search continues for the ideal H. pylori eradication regimen. PMID- 1437953 TI - The evaluation of dizziness in elderly patients. AB - Twenty-one elderly patients with dizziness underwent a comprehensive medical and otoneurological evaluation. The majority had vertigo, limited mobility and restricted neck movements. Poor visual acuity, postural hypotension and presbyacusis were also frequent findings. Electronystagmography revealed positional nystagmus in 12, disordered smooth pursuit in 18, and abnormal caloric responses in nine. Magnetic resonance imaging showed ischaemic changes in six out of eight patients. Although dizziness in the elderly is clearly multifactorial, the suggested importance of vertebrobasilar ischaemia warrants further consideration as vertigo has been shown to be a risk factor for stroke. PMID- 1437954 TI - Influence of cigarette smoking on the outcome of coronary care unit admissions with chest pain. AB - We studied the effect of current smoking habits in the period immediately before admission to hospital in 90 consecutive patients presenting with chest pain, 50 of whom were shown to have myocardial infarction. Urine cotinine/creatinine (cot/creat) ratio measured within 4 hours of admission was used as an objective marker of cigarette smoking in the preceding 18 hours. Fifty-seven patients had urine cot/creat ratios suggesting recent smoking, although four of these denied smoking. Patients with myocardial infarction had higher median cot/creat ratios (3.31 micrograms/mg, range 0-17.8) compared with patients with non-infarct chest pain (0.5 microgram/mg, range 0-37.2). Sixteen patients with cardiac rhythm disturbances following infarction had significantly higher cot/creat ratios than the 34 infarct patients without this complication (median and range 8.34 micrograms/mg; 0-17.8 V. 1.87 micrograms/mg; 0-16.4, P < 0.01). Tobacco use in the 24 hours before myocardial infarction may predispose to cardiac rhythm disturbance, irrespective of infarct size. PMID- 1437955 TI - Behcet's syndrome in Scotland. AB - We present the clinical details and HLA typing of 15 Celtic Caucasian patients (four male, 11 female) with Behcet's syndrome (International Study Group criteria). The males affected were younger than the affected females, and three of these males had severe uveal involvement. Two of the 15 patients had the A2 Bw6 Dr4 haplotype but this did not confer family penetrance. Eight had gastrointestinal involvement: two females required ileostomy, two females had chronic diarrhoea, one female had severe ileitis and oesophageal lesions, two males had peptic ulcers, and one female had a peptic ulcer and primary biliary cirrhosis. All of those who developed gastrointestinal symptoms had either the Dr4 or the Dr7 antigens. This study is the largest HLA survey of Celtic Caucasians with Behcet's syndrome. The clinical features and HLA haplotypes are markedly different from 'Arab' and 'Japanese' varieties of Behcet's syndrome. The expression of the Dr4 and Dr7 antigens in those with gastrointestinal involvement possibly implicates class II antigens (Dr) in the pathogenesis of the manifestations of Behcet's disease in the bowel. PMID- 1437956 TI - Peptic oesophageal stricture: an age-related problem? AB - A one year retrospective study of 76 patients with peptic oesophageal stricture was performed. Analysis of results showed a significant age-related risk of developing peptic oesophageal stricture. Possible age-related risk factors are discussed. Pitfalls in diagnosis and management are highlighted and the role of H2 receptor antagonists, antacids and omeprazole are discussed. PMID- 1437957 TI - One year experience in the treatment of familial hypercholesterolaemia with simvastatin. AB - Patients with heterozygous familial hypercholesterolaemia (FH) have a substantially increased risk of atherosclerosis due to very high plasma levels of cholesterol. Recent evidence has shown that coronary heart disease in these patients may regress with lipid-lowering therapy. In this study the efficacy and safety of simvastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A, was investigated in 30 patients with FH over a period of one year. Substantial reductions in the plasma concentrations of total cholesterol (-28%), low-density lipoprotein (LDL) cholesterol (-32%), intermediate-density lipoprotein (IDL) cholesterol and apolipoprotein (apo) B (-33%) were achieved with 20 mg/day of simvastatin; there were no significant changes in triglycerides high-density lipoprotein cholesterol or apo A. In contrast to previous studies, 40 mg/day of simvastatin did not result in a further statistically significant fall in LDL cholesterol, IDL cholesterol or apo B in the group as a whole. The drug was well tolerated and no adverse clinical or laboratory events were recorded. In particular, no ophthalmological, hepatic or renal disorders were observed and there were no sleep disturbances. We conclude that simvastatin is an efficacious and safe drug to treat patients with heterozygous FH and that rarely will the dose need to be increased above 20 mg/day. PMID- 1437958 TI - Is bed rest useful after diagnostic lumbar puncture? AB - A randomized study of 110 patients undergoing their first diagnostic lumbar puncture was performed to compare the effect of immediate mobilization with 4 hours bed rest on the incidence of post lumbar puncture headache. There was no difference between the mobile (n = 54) and bed rest (n = 56) groups in the incidence of post lumbar puncture headache (32% versus 31%, respectively). We conclude that bed rest following lumbar puncture may be an unnecessary imposition on the patient, as well as on nursing staff. PMID- 1437959 TI - Cerebellar manifestations of prostatic carcinoma. AB - We present two patients known to have prostate cancer who presented with acute cerebellar signs. The neurological deficit of the first patient was due to a paraneoplastic cerebellar manifestation and progressed, despite evidence of response of the primary prostate tumour to hormonal manipulation. The second case, resulting from a solitary cerebellar metastasis, was amenable to surgical intervention and subsequent hormonal manipulation. This latter patient has experienced no recurrent neurological signs after a period of 7 years follow-up. This is the first report of a paraneoplastic cerebellar deficit and, to our knowledge, only the sixth case of parenchymatous cerebellar metastasis of prostatic origin to appear in the literature. PMID- 1437960 TI - Bilateral carpal tunnel syndrome associated with interleukin 2 therapy. AB - We report the development of synchronous bilateral carpal tunnel syndrome in a woman with metastatic colorectal cancer, undergoing treatment with recombinant interleukin 2. A carpal tunnel decompression was carried out on the hand which was more severely affected, with a gradual recovery in median nerve function. To the best of our knowledge, this is the first reported case of carpal tunnel syndrome in association with recombinant interleukin 2. PMID- 1437961 TI - Empty sella developing during thyroxine therapy in a patient with primary hypothyroidism and hyperprolactinaemia. AB - A 35 year old woman presented with severe primary hypothyroidism and galactorrhea. A very high prolactin level was also detected and computerized tomography scan of the sellar region demonstrated an enlarged pituitary gland associated with contrast enhancement. Replacement therapy with thyroxine corrected both biochemical and clinical abnormalities but empty sella developed during this therapy. It is concluded that empty sella may be related to thyroxine induced shrinkage of lactotroph and/or thyrotroph cell hyperplasia. PMID- 1437962 TI - Suppurative thyroiditis with oesophageal carcinoma. AB - A 68 year old, previously well woman presented with dysphagia, weight loss and a neck swelling. Investigations revealed a right-sided thyroid abscess with fistulous connection to the upper of two oesophageal carcinomas, a previously unreported association. The resistance of the thyroid to infection and the mechanisms of thyroid abscess formation in this patient are discussed. PMID- 1437963 TI - Doppler echocardiography in elderly patients with ejection systolic murmurs. PMID- 1437964 TI - The genes for Noonan's syndrome, woolly hair and ulerythema ophryogenes. PMID- 1437965 TI - Primary malignant neoplasms associated with chronic lymphocytic leukemia. PMID- 1437967 TI - The effect of meal feeding on small intestine weight. AB - Two trials were conducted using feed forms of pellets and mash to determine whether parts of the digestive tract (small intestine) were enlarged by meal feeding. Results obtained show that meal feeding of broilers significantly increases small intestine weight for both mash and pellet broiler groups when compared with continuously fed broilers. The body weight, feed conversion, and mortality did not differ between the continuous-fed versus meal-fed groups. Pelleting the diet during the growing period (3 to 6 wk of age) significantly improved both growth rate and feed conversion of broilers. PMID- 1437966 TI - Antibody responses to combinations of antigens in white Leghorn chickens of different background genomes and major histocompatibility complex genotypes. AB - Antibody responses in chickens to SRBC, Newcastle disease (NDV), and Brucella abortus (BA) were compared when given singly or in combination. Chickens used in the present experiment originated from a cross and then backcrossing of White Leghorn populations that had been selected for high (HA) or low (LA) antibody response to SRBC antigens. The populations used in the current study were segregating for MHC haplotypes B13 and B21. The experiment had a 2 x 3 x 6 factorial arrangement of treatments (two background genomes: HA and LA; three MHC haplotypes: B13B13, B13B21, and B21B21; and six antigen treatments: SRBC, NDV, or BA only, SRBC plus NDV, SRBC plus BA, and NDV plus BA). Antigens were administered either i.v. (SRBC) or i.m. (NDV and BA) when chicks were 42 days of age. Blood was obtained 27 days later (69 days of age) for antibody determinations. A significant background genome by MHC haplotype interaction for BA antibodies was due to relatively high titers in Line HA chickens of MHC genotypes B13B13 and B13B21. Background genome by MHC genotype interactions were not significant for SRBC or NDV antibodies. Antibody titers to SRBC were higher in background genome HA than LA, and similar among MHC genotypes. Antibodies to NDV were lower in chickens of MHC genotype B21B21, but there were no differences due to background genome. For each of the three antigens, antibody responses were highest when administered singly rather than in combination. Antibody titers were lower for SRBC when given with BA, and for BA titers when given with NDV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437968 TI - Yolk sac absorption and initiation of growth in broilers. AB - A series of three experiments was conducted to determine the role of the yolk sac in initiation of growth in broilers. In Experiment 1, absorption of the yolk sac was found to precede initiation of growth in newly hatched broilers by approximately 24 h. Because the yolk sac is essential for early initiation of growth, in Experiments 2 and 3 it was removed and diets with incremental fat levels of 3, 6, and 10% were fed to assess whether fat was essential for optimal growth during the neonatal period. Results suggest that dietary fat has its greatest effect on growth after 10 days of age. Therefore, initiation of growth may be more closely dependent upon other nutrients. PMID- 1437969 TI - Effects of light sources and the presence or absence of males on reproduction of female breeder turkeys. AB - The effects of sodium vapor (SV), daylight fluorescent (DF), and incandescent (IN) light sources and the influence of the presence or absence of males on reproduction of female turkeys were evaluated. Hens under SV and DF lights consistently laid more eggs than those under IN lights. There were no significant differences in hen-day egg production among hens in the physical presence of males and hens allowed visual and vocal contact with males. However, hen-day egg production was significantly lower for females in pens in which males were absent. Fertility, hatchability, days to first egg, egg weight, and egg specific gravity were unaffected by light source treatments or by the presence or absence of males in pens of females. PMID- 1437970 TI - Beak trimming effects on beak length and feed usage for growth and egg production. AB - Two experiments were conducted to compare beak treatment effects on pullets of three genetic stocks. Within each stock, equal numbers were assigned to three treatments: no beak trimming (IN), beak trimming once (1X), and beak trimming twice (2X). Beak treatment, genetic stock, and age effects along with interactions among main effects were examined for production-associated traits during rearing and brief periods of early egg production. Beaks of 1X and 2X pullets remained shorter than those of IN pullets through final measurements at 36 and 32 wk of age in Experiments 1 and 2, respectively. However, differences in beak length decreased as age increased. Upper beaks of 2X pullets remained shorter than those of 1X pullets, but lower beaks of 1X and 2X pullets did not differ by 20 wk in Experiment 2. Weight gains, feed usage, and efficiency of growth were affected by beak treatments. Beak trimming reduced gains, feed eaten, feed wasted, and total feed used, and 2X pullets used their feed more efficiently for weight gain and egg production. A general decrease occurred in differences among beak treatments for weight gains, feed eaten, feed wasted, and efficiency of gains with increasing age during rearing. Nevertheless, significant differences in feed consumed, feed wasted, and efficiency of feed used for egg production indicated an economic advantage in favor of beak trimming. PMID- 1437971 TI - Effect of induced molting on the course of infection and transmission of Salmonella enteritidis in white Leghorn hens of different ages. AB - Previous work in the authors' laboratory had shown that inducing molt using a 2 wk feed removal protocol in 58- to 84-wk-old White Leghorn hens increased the severity of intestinal infection by Salmonella enteritidis (SE). As susceptibility to infection can be influenced by age, a study was conducted to compare the effect of the feed removal on infection by SE in 20-, 40-, and 74-wk old hens. Birds were orally infected with 5 to 10 x 10(6) SE on Day 4 of fast and were sampled for SE shedding 3, 10, 17, and 24 days later. Significantly higher numbers of SE were shed in fasted birds on Day 3 (20 and 40 wk of age), Day 10 (40 and 74 wk of age), and Day 17 (74 wk of age). Transmission of SE to uninfected, contact-exposed birds was observed in all three trials for both the fed and fasted groups. However, significantly more fasted contact-exposed birds became positive for SE on Day 3 (20-wk-old), Day 10 (74-wk-old), and Day 17 (74 wk-old). Significantly more SE was also shed in these fasted contact-exposed birds on Day 3 (20-wk-old), Day 10 (all age groups), and Day 17 (74-wk-old). The current results indicate that the fasting conditions used to induce a molt in hens increase the shedding of SE in direct-infected and contact-exposed hens and this effect does not appear to be affected by age. PMID- 1437972 TI - Multivariate epidemiological approach to coccidiosis in broilers. AB - A retrospective, case-control study into risk factors of coccidiosis was undertaken using data from 189 broiler flocks. A case flock was defined as a flock in which at least one bird had intestinal lesions on 1 of 6 wk in a 42-day cycle. Flocks wherein such birds could not be detected were defined as controls. There were 187 variables, measured or derived. These were assigned to subsets of data, each subset being a group of variables representing related information. Uni- and bivariate analyses were performed in each subset. Variables and interactions that were significant in these analyses were entered into a multivariate model across subsets. In the final model, seven variables appeared to be significantly associated with detecting lesions in birds of a flock. Differences among breeds covered a range of about an 80-fold change in risk of being a case. At intermittent lighting, the risk of being a case increased about sevenfold compared with continuous lighting. A higher initial (Week 1) environmental temperature decreased the risk of finding lesions in a flock (about .8-fold per degree Celsius). This risk was also lower at a lower average aerial ammonia content (below versus above 14 ppm) and higher maximum carbon dioxide content (above versus below .4 vol%) changing the risk about .3- and .4-fold, respectively. The risk of being among cases increased with more litter (about twofold per kilogram of litter per square meter). Flocks in houses of 600 to 800 m2 were about 9.8 times more at risk of being scored as lesion-positive than those in smaller houses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437973 TI - Differential resistance to Staphylococcus aureus challenge in major histocompatibility (B) complex congenic lines. AB - Ten inbred B-congenic Leghorn lines were challenged with two isolates of Staphylococcus aureus at 3 days and 6 wk of age. Significant differences in mortality were observed among such lines when challenged at 3 days with either S. aureus Isolate P4L (moderately pathogenic) or S. aureus Isolate 3727 (highly pathogenic). Line 331 (B2/B2 genotype) had lower mortality than either Line 004 (B17/B17, chi 2 = 4.13, P < .05) or Line 253 (B18/B18, chi 2 = 4.23, P < .05) challenged with Isolate P4L. The use of a susceptibility index allowed for the detection of additional differences among the various lines challenged by Isolate 3727. Line 336 (BQ/BQ) was more resistant than either Line 335 (B19/B19, P < .01) or Line 330 (B21/B21, P < .01). No significant differences were found among the lines challenged at 6 wk by either isolate. The results provide additional evidence for the importance of the B complex in genetically determined disease resistance, and further demonstrate the usefulness of congenic lines in such investigations. PMID- 1437974 TI - Valine deficiency. 1. The effect of feeding a valine-deficient diet during the starter period on performance and feather structure of male broiler chicks. AB - Experiments were designed to investigate the effect of feeding diets deficient in one or more of the three branched-chain amino acids (BCAA) on the performance of 3-wk-old male broilers. In the first experiment, levels of .96 and 1.46% Leu, .52 and .82% Ile, and .65 and .95% Val were used. Feeding the lowest combination of the three BCAA resulted in weight gain (WG) and feed conversion ratio (FC) of 344 g and 1.59 g:g, respectively. These parameters were not improved by adding dietary increments of the three BCAA individually. The greatest response, however, for both WG (435 g) and FC (1.41 g:g) was obtained by the addition of the three BCAA simultaneously. Chicks fed the low-Val diets in combinations with added levels of Ile and Leu exhibited feather and leg abnormalities. A second experiment was designed to investigate the effect of Val deficiency on feather protein, feather amino acids, and calcium content of the bone. Three treatments were used: a BCAA-deficient diet with .96% Leu, .52% Ile, and .63% Val; a Val deficient diet, which contained 1.37, .82, and .63% of Leu, Ile, and Val, respectively; and a Val-supplemented diet, which was the same as the previous diets except that the Val content was .83%. Valine deficiency significantly decreased WG (243 g), FC (1.69 g:g), bone calcium (134 mg/g dry bone), and feather protein (82.7% of wet weight). Valine deficiency also decreased the level of Cys in feathers, but increased those of Asp, Glu, Met, Tyr, His, and Lys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1437975 TI - Valine deficiency. 2. The effect of feeding a valine-deficient diet during the starter period on performance and leg abnormality of male broiler chicks. AB - Using force-feeding and pair-feeding techniques, two experiments were conducted to investigate the problem of leg abnormality associated with feeding a Val deficient diet as compared with a diet deficient in all the branched chain amino acids (BCAA) or a Val-supplemented diet. The BCAA-deficient diet contained .96, .52, and .63% of Leu, Ile, and Val, respectively. The Val-deficient diet contained 1.37 Leu, .82 Ile, and .63% Val. The Val-supplemented diet contained 1.37 Leu, .82 Ile, and .83% Val. In both studies birds fed the Val-supplemented gained more weight than birds in the other two groups. Although birds on Val deficient and BCAA-deficient diets had similar weight gain, the former were lethargic and showed feather and leg abnormalities. Bone ash and bone calcium for Val-deficient birds were the lowest among the three groups studied (P < .05). The levels of the BCAA in plasma reflected those of the treatment diets. Plasma hydroxyproline was lowest in birds fed the Val-deficient diet (P < .05), indicating a reduction in bone collagen breakdown. Kidney function measurements were the same for birds on the Val-supplemented and Val-deficient diets. Fractional excretion of calcium in Val-deficient birds (.13%), however, was three times higher than that of Val-supplemented birds (P < .05). The results indicated that Val deficiency per se increased calcium excretion in urine and induced leg abnormality in young chickens. PMID- 1437976 TI - Response of male turkeys hatched from first-cycle and force-molted breeder hens to a regimen providing progressive feeds by weight and the value of increased lysine prior to marketing. AB - Male poults originating from 41- and 85-wk-old Nicholas Large White breeder turkey hens were compared using a six-feed system provided on the basis of weight. Each source of poult was compared further in its response to lysine at .65 and .80% in the final feed (14.5% CP and 3.40 kcal AMEn/g) before marketing at 18 wk of age. Poults from 85-wk-old hens were heavier at placement than those from 41-wk-old hens. Equalization of body weights occurred once the allotment of starting feed had been consumed and for the most part remained similar thereafter. Increasing lysine content of the final feed did not improve body weight of both sources of birds at marketing (P < .13). Feed conversions included accrued mortality, and treatment differences were not apparent. Commercial processing of the flock and measurements on sample birds indicated no ready differences in chilled carcass yield nor proportions of parts occurred among treatments. The overall effects of breeder age with the progeny were negligible, and the .65% level of lysine that presently serves as the 1984 National Research Council minimum requirement when associated with 14% CP and 3.30 kcal/g appears to be adequate for the Nicholas strain of turkey from 16 to 18 wk of age. PMID- 1437977 TI - Effect of heat stress on 2-hydroxy-4-(methylthio)butanoic acid and DL-methionine absorption measured in vitro. AB - The objective of the present experiments was to determine the biochemical basis for preliminary chick performance data, which indicate an ameliorative effect of 2-hydroxy-4-(methylthio)butanoic acid (HMB) when compared with DL-methionine (DLM) fed during hot conditions. In vitro passage of HMB or DLM across intact segments of small intestine from either control (thermoneutral, TN) or heat stressed (HS) birds was used as a model for intestinal absorption. For DLM placed in the lumen, appearance in the outside buffer was reduced when using intestine from HS birds compared with tissue from TN birds. In contrast, the appearance of HMB in the outside buffer was greater using HS intestine, resulting in a substrate by environment interaction (P < .01). Slices of everted small intestine from TN and HS birds were used to study epithelial uptake of methyl labeled 14C DLM by three transport pathways: diffusion, carrier-specific energy- and sodium independent uptake (ESI), and carrier-specific energy- and sodium-dependent uptake (ESD). Correcting for extracellular volume, total epithelial uptake of 14C DLM (diffusion plus ESI plus ESD) was reduced by 34% in HS intestine (P < .05). Energy-dependent uptake was observed to decrease by 87% in HS (P < .05). Energy independent uptake was increased (136%, HS versus TN, P < .05), but not enough to compensate for the decrease in ESD uptake. Intestinal transport systems for glucose and leucine were also observed to change during HS, suggesting a role for cellular transport changes in the performance reduction associated with HS. PMID- 1437978 TI - Identifying genes involved in the variability of genetic fatness in the growing chicken. AB - A precise knowledge of the genome involved in the expression of a quantitative trait could provide a useful tool in breeding programs; molecular genetic methods are capable of yielding this kind of information. An experimental procedure is presented here for identifying genes whose expression is related to weight variability of abdominal adipose tissue in the growing chicken. Quantitative traits are the result of metabolic pathways exhibiting some major regulation stages that are controlled genetically. These steps involve genes that may act as "major genes". With regard to chicken fat metabolism, most fatty acids are synthesized in the liver and incorporated into very low density lipoprotein (VLDL) particles before their secretion into the plasma. Accordingly, the present study focused on the expression of liver genes. The mRNA of lipogenic enzymes (acetyl-coenzyme-A carboxylase, fatty acid synthase, malic enzyme, and delta 9 desaturase) were analyzed. Also studied were apoprotein (apo)A1, apoVLDL-II, and apoB mRNA from 9-wk-old male chickens from two lines selected for high and low abdominal fat pads. Significant differences for apoA1 mRNA levels occurred between fat and lean birds. Moreover, the total quantity of mRNA provided an accurate estimation of the abdominal fat pad (r = .74 with P < .05). PMID- 1437979 TI - The effect of testosterone propionate on growth of broiler chickens. AB - The effects of testosterone propionate (TP) on body weight, tissue percentages of body weight, serum IgM, and rectal temperature (2 h postinjection) of male and female broiler chickens were investigated at 28 and 48 days posthatching. Testosterone propionate was dissolved in sesame oil and was injected at 2 mg/kg of body weight every other day, and controls were treated with sesame oil at similar volume, starting Day 7 posthatching. Administration of TP reduced (P < .05) body weight and percentages of liver, testes, and bursa of Fabricius at 28 and 48 days of age. At 28 and 48 days of age, muscle percentage and comb growth of TP-treated birds increased (P < .05) but ovarian weight was unaffected. Concentrations of IgM in serum of TP-injected birds was unchanged at Day 28, but increased (P < .05) at Day 48. Testosterone propionate did not affect percentages of bone or abdominal fat in either sex. Rectal temperature was depressed (P < .05) by TP treatment in both sexes at both ages. PMID- 1437980 TI - Cross-reactivity of sperm-binding proteins from chicken, turkey, and duck oocytes. AB - Binding and penetration of spermatozoa through the perivitelline layer (PL) overlying the hen's ovum have been studied more frequently in the chicken than in other domesticated avian species. Species-specific action of the binding process was tested using an in vitro competition assay in which spermatozoa from the cock, tom, and drake were pretreated with solubilized PL protein (PL-P) from the chicken, turkey, and duck ovum. Spermatozoa were pretreated with PL-P for 20 min at 39 C and co-incubated in vitro with a .5 cm2 section of intact PL from the homologous sperm donor species for an additional 10 min at 39 C. Effectiveness of PL-P pretreatment was assessed quantitatively by the number of spermatozoa bound to the PL, and was expressed as a percentage of the control [minimum essential medium (MEM) pretreated sperm = 100%] binding. Pretreatment of cock spermatozoa with chicken, turkey, or duck PL-P resulted in 21, 40, and 48% binding, respectively. Similarly, pretreatment of tom spermatozoa with PL-P from chicken, turkey, or duck resulted in 45, 51, and 39% binding, and that of drake spermatozoa resulted in 38, 32, and 21% binding, respectively. Incubation of spermatozoa with PL-P from chicken, turkey, and duck ova indicated cross reactivity and suppression of binding between avian spermatozoa and PL that was not species-specific. PMID- 1437981 TI - Sex differences in incubation length and hatching weights of broiler chicks. AB - Two experiments were run using broiler eggs (Peterson x Arbor Acres) to determine whether sex differences exist in incubation time required to hatch males and females and in various measures of chick weight (CW). Relationships between measures of CW and incubation time and between CW and egg weight (EW) were determined. Chicks that had emerged from eggs were removed from the hatcher at approximately 6- (5 to 8) h intervals between 490.5 and 527.5 h of incubation in Experiment 1 and at about 2-h intervals between 483 and 524 h of incubation in Experiment 2. Chicks were weighed before and after removal of the residual yolk sac immediately upon removal from the hatcher. In both experiments, a preponderance of early-hatching chicks were female. The time at which 50% of the females had hatched was significantly (P = .05) earlier than the 50% hatch time for males (2.68 and 3.32 h in Experiments 1 and 2, respectively). About 71% of the females had hatched by 504 and 509 h in Experiments 1 and 2, whereas only 57 and 52% of the males had hatched at comparable times. In Experiment 2, the yolk free CW (YFCW) of males tended to be greater than that of females (P = .07) and the YFCW expressed as a percentage of EW was significantly (P = .007) greater. The regression of CW and YFCW on EW were highly significant and positive in both experiments. There was a significant relationship between EW and time required to hatch for males in Experiment 1 only. PMID- 1437982 TI - Analysis of the combined effect of the spermatozoal degeneration allele (Sd) and homozygosity of the rose comb allele (R) on the duration of fertility of roosters (Gallus domesticus). AB - Roosters homozygous for the rose comb allele (R/R) are subfertile. Likewise, roosters bearing the dominant spermatozoal degeneration allele (Sd) are subfertile. The objective of the present research was to see whether these effects were cumulative. Domestic fowl were bred in order to obtain males representing the following genotypes: R/r+ sd+/sd+, R/r+ Sd/sd+, R/R sd+/sd+, and R/R Sd/sd+. Duplicate fertility trials were conducted with Single Comb White Leghorn hens. In each trial, ejaculates were pooled according to genotype. The insemination dose was 1 x 10(8) viable spermatozoa per hen, and eggs were collected over a 21-day interval following a single intravaginal insemination. Fertility over the 21-day period was 53 +/- 2.1 (SEM), 36 +/- 1.6, 21 +/- 2.1, and 11 +/- 1.2%, respectively. Therefore, the effect of homozygosity for the R allele and the presence of the Sd allele were cumulative in the depression of fertility. PMID- 1437983 TI - Research note: effect of in ovo 17-beta-estradiol or tamoxifen administration on sexual differentiation of the external genitalia. AB - The effect of in ovo administration of tamoxifen or 17 beta-estradiol on external sexual dimorphism in chickens was investigated. In two trials, fertile eggs were injected with either tamoxifen (200 micrograms per egg) or vehicle (100 microL corn oil) on Day 1 of incubation, or with 17 beta-estradiol (20 micrograms per egg) or vehicle on Day 11 of incubation. Sexes were determined by visual inspection of the external genitalia and by gonadal identification at Day 1 posthatch. Tamoxifen injection resulted in a significantly greater number of phenotypic male identifications, with male:female ratios of 76:24 (Trial 1) and 62:38 (Trial 2) based on external genitalia phenotype. Gonadal sexing corrected these ratios to 46:54 and 44:56, resulting in genital sexing errors of 27% (Trial 1) and 18% (Trial 2). These errors were significantly higher than genital sexing errors of the chicks treated with vehicle (2 and .6% for Trials 1 and 2, respectively). In ovo administration of 17 beta-estradiol resulted in an increased number of female identifications based on genital sex determination, with male:female ratios of 37:63 (Trial 1) and 46:54 (Trial 2). Gonadal sexing corrected these ratios to 54:46 and 51:49, resulting in genital sexing errors of 10 and 6% for Trials 1 and 2, respectively. These errors were significantly higher than genital sexing errors of vehicle-treated chicks (4 and .9% for Trials 1 and 2, respectively). The results of the present study indicate that early embryonic administration of estrogen or an estrogen antagonist alters chicken external sexual dimorphism near the time of hatch. PMID- 1437984 TI - Research note: a lack of response to pantothenic acid supplementation to a corn and soybean meal broiler diet. AB - Two 21-day battery studies were conducted to determine whether a corn and soybean meal diet without pantothenic acid supplementation was adequate for growth and feed efficiency of broilers. In each experiment, 64 1-day-old broiler chicks (32 male and 32 female) were assigned to each of six dietary treatments. The basal diet was supplemented with 0, .3, .6, 2.4, 4.8, and 14.4 mg of supplemental pantothenic acid/kg of diet. Each diet in both experiments was fed to eight pens containing four females and four male day-old Arbor Acres broiler chicks. The basal diet contained 22.3% protein and 4.74 mg/kg pantothenic acid by analysis. No improvement in growth or feed efficiency was obtained from any level of pantothenic acid supplementation. PMID- 1437985 TI - Research note: the reactivity of anti-chondroitin sulfate antibody to comb and wattle galactosaminoglycans. AB - The current study was undertaken to examine the reactivity of anti-chondroitin sulfate monoclonal antibody, CS-56, to the comb and wattle galactosaminoglycans containing varying proportions of L-iduronic acid. Galactosaminoglycans were isolated from mature rooster comb and wattle tissues and were separated into four fractions (I, II, III, and IV), which were precipitable with 18, 25, 40, and 50% ethanol, respectively. Each fraction was examined using an ELISA technique. The results demonstrated presence of CS-56 epitope in galactosaminoglycans from both tissues. Most (> 99%) of the epitope were found in Fractions III and IV, which were galactosaminoglycans rich in D-glucuronic acid. Fractions I and II, which were dermatan sulfates rich in L-iduronic acid, showed little or very weak antigenicities. PMID- 1437986 TI - Research note: effects of beak trimming and genetic stock on rate of mash consumption and feeding-related behavior in egg-strain pullets. AB - Pullets whose beaks were trimmed once (at 9 days) and twice (at 9 days and 9 wk) were able to ingest feed, in the form of mash, more rapidly under competitive feeding conditions and at least as rapidly in the absence of competition as pullets with intact beaks. Tests of feeding rate, when pullets fed in groups, were carried out after a feed deprivation period of 7 h at ages of 10 through 16 wk. Similar tests were done at 18 wk, when pullets fed without competition. Genetic stock and age had significant effects on frequency of agonistic acts at the feeder and displacements from the feeder during 5-min tests under competitive feeding conditions. Age influenced the number of pullets feeding simultaneously and amount of feed eaten per pullet during the same feeding tests. No interactions were detected among beak treatment, stock, and age for feeding related behaviors or rate of feed consumption during competitive feeding. In noncompetitive feeding tests, genetic stock affected feeding rate but no stock by beak treatment interaction was present. PMID- 1437987 TI - Developmental toxicity of antiepileptic drugs: relationship to postnatal dysfunction. PMID- 1437988 TI - Vasoactive mediators released by endothelins. PMID- 1437989 TI - Tolerability of fibric acids. Comparative data and biochemical bases. AB - Fibric acids are an established class of drugs for the treatment of hyperlipoproteinaemias. Although they have been in use for 30 years or longer, some doubts remain as to their relative tolerability, both as a class and as single agents. Some side effects, e.g. lithogenicity, may be related to their mode of action, while others, e.g. the acute muscular syndrome, may be linked to the spatial conformation of the molecule. These disadvantages should, however, be weighed against the additional, potentially therapeutic properties shown by these compounds. In particular, effects on maturity onset diabetes and hyperuricaemia, as well as a very interesting fibrinolytic potential, have been described for some of them. A painstaking comparative analysis of the major literature data pertaining to the clinical toxicological profile of these agents allow to conclude that, while belonging to a chemical class, fibric acids show dramatic differences from one another, in terms of side effects and of additional pharmacodynamic activities. Moreover, in the case of lithogenicity for example, considerable differences exist between normo- and hyperlipidaemic subjects. Overall, newer molecules of more sophisticated design have a significantly improved tolerability profile vs the old clofibrate. PMID- 1437990 TI - Polymorphonuclear leucocyte-dependent modulation of platelet function: relevance to the pathogenesis of thrombosis. PMID- 1437991 TI - Platelet-dependent modulation of neutrophil function. PMID- 1437992 TI - Cognitive and noncognitive stress. PMID- 1437993 TI - Presence of tobramycin in kidneys and placentae of Sprague-Dawley rat fetuses and newborns following in utero exposure. AB - The maternal-fetal transfer of tobramycin (TBM) was investigated in the rat by means of a microbiological assay, to assess the presence and amount in the kidneys and placentae of fetuses at gestational day (GD) 20, in the kidneys of newborns 6 and 11 days after the end of treatment and in the kidneys of the dams. In the qualitative assay, pregnant rats were injected i.p. with 0, 30, 60 mg/kg b.w. of TBM on GD 10-19. A group of dams treated in parallel with 30 mg/kg b.w. was utilized for a microbiological semiquantitative assay. All litters contained some fetuses showing no detectable TBM accumulation in either kidney or in placentae: at 30 mg/kg/b.w. accumulation appeared more prevalent in placenta than in the kidneys of the corresponding fetuses, as confirmed also by the semiquantitative assay. Some newborns (about 6%) of both groups showed detectable renal TBM residues on the 6th and on the 11th day after the end of treatment. The frequency of newborns showing residues was not obviously related to the dose or the day of sampling, and the concentrations of TBM found were comparable to those observed in fetuses. It is possible that they represent a particularly sensitive subgroup. PMID- 1437994 TI - Biosensor development. AB - This article reviews the recent biosensor developments for medical applications, focusing on the various biological recognition elements used in biosensors and the systems transduction mechanisms. Available instruments utilizing biosensor technology are also examined from a commercial perspective. PMID- 1437995 TI - The enantiomers of the valproic acid analogue 2-n-propyl-4-pentynoic acid (4-yn VPA): asymmetric synthesis and highly stereoselective teratogenicity in mice. AB - The teratogenic activities of R(+)- and S(-)-2-n-propyl-4-pentynoic acid (R and S 4-yn-VPA), the enantiomers of the highly teratogenic valproic acid (VPA) analogues (+/-)-4-yn-VPA, were investigated in mice. The enantiomers were prepared via asymmetric synthesis, each in three steps employing the chiral auxiliaries (4R,5S)-4-methyl-5-phenyl-2-oxazolidinone and S-4-benzyl-2 oxazolidinone. The determination of the absolute configurations and the optical purities is described. R(+)-4-yn-VPA contained 7%, and S(-)-4-yn-VPA 8%, of the respective antipodes. The aqueous solutions of the sodium salts of R- and S-4-yn VPA were administered as single i.p. injections during early organogenesis in the mouse (day 8 of gestation) using the induction of exencephaly as the teratological end point. Dose/exencephaly curves indicated that S-4-yn-VPA is 7.5 times more teratogenic than its antipode, 1.9 times more teratogenic than (+/-)-4 yn-VPA and 3.9 times more teratogenic than the parent drug VPA. In contrast, the neurotoxicity (maternal toxicity) of the 4-yn-VPA enantiomers was found to be independent of the stereo-chemical configuration and lower than achieved after VPA administration. Due to its low neurotoxicity and highly stereoselective neural tube-inducing activity, S-4-yn-VPA should prove an important tool for the investigation of molecular mechanism of the teratogenic action in this class of compounds; R-4-yn-VPA could act as the negative control in these studies. PMID- 1437996 TI - Microscopic characterization of particle size and shape: an inexpensive and versatile method. AB - A variety of methods exists for measuring individual particle dimensions as a means of characterizing particle size, size distribution, and shape. The equipment described in this report belongs to the class of semiautomatic non-TV interfaced analyzers. Unlike many existing image analysis systems, three dimensional form measurements and texture data for the calculation of particle size and shape parameters can be determined easily and directly from each particle profile using this system. Essentially all data are collected directly from the particle and recorded by the computer with no intermediate steps. Much of the system consists of general-purpose and relatively inexpensive, commercially available hardware and software. Using this method, particle size, size distribution, and qualitative or quantitative shape information can easily and rapidly be obtained simultaneously. Particle length and width characterization, for example, can take less than 15 min. The equipment is versatile and flexible in measurements and calculations. The size and shape parameters to be measured are determined by the researcher and not the instrument. The ease with which this information can be obtained from small samples early in the development process makes it a valuable tool for the formulator. PMID- 1437997 TI - Sterile filtration of a parenteral emulsion. AB - The Syntex adjuvant formulation (SAF) containing [thr1]-muramyldipeptide in an oil-in-water emulsion has proven to be an effective adjuvant eliciting both cell mediated and humoral immune response. As a parenteral emulsion, sterility of the final product was a concern, and various methods of achieving sterility were considered. For emulsions, most conventional sterilization methods are not viable, requiring the more cumbersome technique of sterilizing individual components and assembling/manufacturing under sterile conditions. Emulsion vehicles were manufactured with various models in the Microfluidizer M110 series. All equipment examined was capable of reducing the average dispersed oil droplet size to approximately 160 nm, with varying size ranges. Operating at an internal equipment pressure of greater than 16,000 psi, with at least five cycles through the interaction chamber, the resulting emulsion had a narrow droplet size range distribution, with the largest droplets being small enough to enable sterile filtration. Under specific-manufacturing conditions, the adjuvant emulsion becomes easily filtered through a 0.22-micron cartridge filter, thus yielding a sterile end product. This is the first published example of emulsion sterilization being achieved by terminal filtration. PMID- 1437998 TI - Dissociation of insulin oligomers by bile salt micelles and its effect on alpha chymotrypsin-mediated proteolytic degradation. AB - Bile salts have been found to be effective absorption promoters of insulin across mucosal barriers, i.e., nasal and gastrointestinal. One of the mechanisms proposed for absorption enhancement is the dissociation of insulin oligomers to monomers, rendering a higher insulin diffusivity. alpha-Chymotryptic degradation and circular dichroism studies were used to characterize such a transition. When zinc insulin (hexamers) and sodium insulin (dimers) were subjected to alpha chymotryptic degradation, a 3.2-fold difference in the apparent first-order rate constants was observed (zinc insulin being slower than sodium insulin), representing the intrinsic difference in the concentration of total associated species in solution (three times). In the presence of a bile salt, sodium glycocholate (NaGC), the rate of degradation of both zinc and sodium insulin increased in an asymptotic manner. A maximum increase of 5.4-fold was observed for zinc insulin at a 30 mM NaGC concentration and a 2.1-fold increase was noted for sodium insulin at 10 mM NaGC, both values being close to the theoretical numbers of 6- and 2-fold as predicted by the complete dissociation of hexamers and dimers to monomers. The result indicates dissociation of insulin oligomers to monomers by bile salt micelles, probably by hydrophobic micellar incorporation of monomeric units. Circular dichroism studies also revealed progressive attenuation of molecular ellipticities at negative maxima of 276, 222, and 212 nm for zinc insulin solution in the presence of NaGC. Therefore, both alpha-chymotryptic degradation and circular dichroism studies have consistently demonstrated that the bile salts may be capable of dissociating insulin oligomers to monomers, a fact which may play an important role in enhancing insulin bioavailability. PMID- 1437999 TI - Effect of zinc binding on the structure and stability of fibrolase, a fibrinolytic protein from snake venom. AB - Fibrolase is a metalloprotease with potential use as a fibrinolytic agent. Loss of the intrinsic zinc atom leads to a rapid decrease in enzymatic activity. Circular dichroism measurements indicate that there is a partial unfolding of an alpha-helical section of the protein concomitant with the loss of zinc. Removal of zinc can be affected by elevated temperatures, acidic pH values, and addition of chelating agents. At low molar concentrations, both ethylenediaminetetraacetic acid (EDTA) and dithiothreitol (DTT) were found to remove zinc efficiently. Analysis of the sequence of fibrolase identified a segment which possessed a high degree of homology with the metal binding site of other zinc proteases, such as thermolysin and the collagenases. However, the putative zinc binding site in fibrolase lacks the additional glutamate ligand found in thermolysin and subtilisin. This sequence is also predicted to adopt an alpha-helical conformation. Together, these data indicate that there is a well-defined metal binding site in fibrolase and that metal binding is the most important factor governing the stability of this protein. PMID- 1438000 TI - Vaginal absorption of insulin in the rat: effect of penetration enhancers on insulin uptake and mucosal histology. AB - The absorption of insulin across the vaginal mucosa into the systemic circulation was studied in ovariectomized rats given subsequent estrogen treatment. Blood glucose levels were determined as an indirect measure of insulin absorption, and the effect of various enhancers on the hypoglycemic response was investigated. In the absence of any enhancer, no decrease in blood glucose levels was observed after vaginal administration of insulin. However, the coadministration of sodium taurodihydrofusidate, polyoxyethylene-9-lauryl ether, lysophosphatidylcholine, palmitoylcarnitine chloride, and lysophosphatidylglycerol significantly increased hypoglycemia, whereas citric acid had little effect. The histological changes in the vaginal epithelium after treatment with the enhancer systems were variable and often severe. While the efficacy of these compounds in promoting the vaginal absorption of insulin is encouraging, their mechanisms of action and long-term histological effects are yet to be defined. PMID- 1438001 TI - The influence of different strains and age on in vitro rat skin permeability to water and mannitol. AB - Water and mannitol were used as test penetrants to study the effect of age on the skin permeability of the Wistar-derived Alderley Park (AP) rat and Sprague-Dawley (SD) rat. Whole-skin membranes were prepared from rats aged 10 to 120 days, while epidermal membranes were prepared from rats aged 24 to 32 days. The results indicated that the skin permeabilities of the two strains were very similar for either whole-skin or epidermal membranes. The influence of age on skin permeability was found to be negligible for the AP rat, and a small decrease in whole-skin permeability was observed for SD rats above 80 days of age. A statistically derived expression ("the separation efficiency factor") was used to determine the optimum age for preparing intact epidermal membranes; these were 26 days for AP rats and 28 days for SD rats. Histological examination of whole-skin membranes for both strains revealed that the stratum corneum and epidermal thickness did not alter significantly with age (10 to 120 days old). Dermal thickness, hair follicle depth, and, to a lesser extent, the surface area occupied by hair follicles all appeared to be influenced by age, although these changes had no detectable effect on skin permeability. PMID- 1438002 TI - Oral delivery of a renin inhibitor compound using emulsion formulations. AB - The oral delivery of O-(N-morpholino-carbonyl-3-L-phenylaspartyl-L- leucinamide of (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylhetane (I), a new renin inhibitor, was studied in the in vivo rat model using emulsion formulations. The components of the emulsion formulations were chosen based on their proposed effects on membrane structure, membrane fluidity, and solute transport. The percent absolute bioavailability (%AB) of I was increased from 0.3% (water suspension) to 5.1% when long-chain unsaturated fatty acid (oleic acid, linoleic acid, etc.)- and mono- and diglyceride (monolein, dilaurin, etc.)-containing emulsion formulations were used. Considering very high first-pass liver extraction of the compound (80%), it is suggested that emulsion formulations increased the intestinal transport of the compound significantly. The solubility of I in aqueous media with and without bile salt (20 mM) was found to be low (approximately 1 micrograms/ml). Incubation in 0.01 N HCl did not affect the particle size of the emulsion. The titration of oleic acid/monoolein emulsion in a pH 6.5 medium with a mixed bile salt system indicated reduction in the particle size of the emulsion. Drug precipitation was observed above 30 mM bile salt concentrations. No drug crystals could be detected in the intestinal contents of the rats when emulsion formulations were ingested. These results suggest that in the intestine of the animals, the particle size of the emulsions is reduced in the presence of bile fluid while the drug resides primarily in the oil phase. The mechanism of enhanced transport of I from the emulsion formulations is discussed along with the possibility of cotransport for the drug and oil. Emulsion formulations can be a potential delivery form for low-bioavailable lipid-soluble drugs. PMID- 1438003 TI - Intestinal water and solute absorption studies: comparison of in situ perfusion with chronic isolated loops in rats. AB - The effects of lumenal glucose on jejunal water transport and the influence of glucose-induced water absorption on solute uptake from single-pass perfusions are compared in anesthetized rats in situ and isolated chronic loops in unanesthetized rats in vivo. While the magnitudes of solute membrane permeabilities are consistently higher in the chronic loop system, the effects on water transport and its promotion of jejunal solute uptake are comparable between the two experimental systems. The effect of glucose-induced water absorption on the enhanced/baseline jejunal uptake ratio of the hydrophilic drug, acetaminophen, is greater than that for the lipophilic drug, phenytoin, in both experimental systems. The fact that chronic loop effective solute permeabilities were equivalent to solute membrane permeabilities in situ is consistent with greater lumenal fluid mixing in vivo. In addition, in situ body temperature affects the uptake of phenytoin but not acetaminophen, water, or glucose. This suggests that active and paracellular solute transport is not compromised in situ, while membrane partitioning and diffusion of lipophilic species are more sensitive to experimental conditions. PMID- 1438004 TI - Absorption of flurbiprofen in the fed and fasted states. AB - The oral absorption of flurbiprofen, an antiinflammatory nonsteroidal compound, was compared in the fasted vs the fed state. When ingested as an aqueous solution of the sodium salt, absorption kinetics followed a monoexponential pattern in half of the subjects and a bimodal pattern with a lag time before the onset of the second phase of absorption in the other half of the subjects. When ingested in the free acid form as a tablet either with water (fasted state) or with water 15 min after 330 ml of apple juice (fed state), flurbiprofen absorption was always bimodal, and the lag time before the onset of the second phase was shown to be dependent on the gastric emptying time (r = 0.623, P less than 0.01). The gastric emptying times were significantly longer when the drug was administered in the fed state (average GET = 57 min in the fasted state and 102 min in the fed state; P less than 0.01). These results suggest that gastric emptying effects are one important way in which absorption of drugs can be affected by meal intake. PMID- 1438005 TI - Effect of chronic administration of phenobarbital on the hepatobiliary transport of phenol red: assessment by statistical moment analysis. AB - The effect of enzyme induction on the hepatobiliary transport of phenol red (PR) in rats was investigated by application of a new analytical system to determine local drug disposition based on statistical moment theory (T. Kakutani et al., J. Pharmacokin. Biopharm. 13:609-631, 1985). Employing the moment parameters obtained from the time courses of plasma and biliary concentrations of PR and its metabolite after intravenous injection, the hepatobiliary transport of PR was theoretically assessed by separating it into component subprocesses such as hepatic uptake, hepatobiliary transfer, and intrahepatic metabolism. The results demonstrated that the acceleration of plasma disappearance of PR caused by pretreatment with phenobarbital (PB), known to induce hepatic enzyme systems, could be attributed to elevation of both hepatic and extrahepatic clearances. While PB did cause bile flow elevation (choleresis) and increased metabolism, these effects were shown to make little contribution to accelerated plasma disappearance of PR, since it was shown that the hepatobiliary excretion of PR was rate-limited by the intrahepatic transfer process, which was unaffected by PB treatment. From the results of this study, this experimental/analysis methodology seems to be useful in obtaining detailed information about hepatobiliary transport of the drug from in vivo data. PMID- 1438006 TI - An in vitro pharmacodynamic model to simulate antibiotic behavior of acute otitis media with effusion. AB - The purpose of this investigation was to develop an in vitro pharmacodynamic model (IVPM) that would simultaneously simulate in vivo serum and middle ear amoxicillin pharmacokinetic characteristics of acute (purulent) otitis media and then utilize the IVPM to assess amoxicillin-mediated killing of a type 7F Streptococcus pneumoniae (MIC = 0.002 mg/L). The IVPM consisted of a sterile central compartment and a membrane-bound "infected" peripheral compartment. Peak peripheral compartment amoxicillin concentrations occurred within 2 hr after its introduction into the central compartment and were approximately 30% of peak central compartment concentrations. Amoxicillin elimination from the central compartment was designed to provide a 1-hr t 1/2. Amoxicillin elimination from the peripheral compartment was slower than from the central compartment, with an average half-life of 2.3 hr. Significant concentration-related differences in maximal bacterial kill rates were not detected over the range of amoxicillin concentrations studied (0.26 to 14.6 mg/L). However, at peak central compartment amoxicillin concentrations of less than or equal to 2 mg/L, a lag phase in killing was observed. In general, the in vitro pharmacokinetic data derived from this model compare well with published in vivo data. PMID- 1438007 TI - Bioequivalence. AB - The bioequivalence of two formulations of the same drug may be determined by evaluating the similarity of their respective plasma concentration curves. The similarity of two plasma concentration functions can be measured by an index called the bioequivalence index. This paper shows how such an index may be defined and calculated. PMID- 1438008 TI - Method for the determination of diphenhydramine in rabbit whole blood by high performance liquid chromatography (HPLC) with ultraviolet (UV) detection in conjunction with gas chromatography (GC) with mass selective detection (MSD). AB - An HPLC/GC-MSD method for the determination of diphenhydramine in rabbit whole blood has been developed and validated. This method is based on a liquid-liquid extraction and reversed-phase chromatography with ultraviolet absorbance detection monitored at 258 nm. HPLC eluant fractions containing diphenhydramine and the internal standard, orphenadrine, were collected, reextracted, then subjected to GC-MSD analysis. Whole blood was utilized, thereby decreasing the required sample volume and increasing the sensitivity of the assay. Diphenhydramine concentrations can be quantitated over a range of 1 to 1000 ng/ml whole blood. PMID- 1438009 TI - Investigation of the degradation mechanism of 5-aminosalicylic acid in aqueous solution. AB - The solution degradation of the antiinflammatory agent 5-aminosalicylic acid (5 ASA) was investigated in order to elucidate a mechanism for degradation. Two degradation pathways were considered: decarboxylation by analogy to 4 aminosalicylic acid (4-ASA) decomposition and oxidation from consideration of 5 ASA's aromatic ring substitution pattern (i.e., relation to p-aminophenol). The oxidation of 5-ASA was investigated using cyclic voltammetry and flow electrolysis. These studies showed that 5-ASA is more easily oxidized than is 4 ASA and that 5-ASA undergoes a two-electron, two-proton oxidation consistent with formation of 5-ASA-quinoneimine (5-ASA-QI). This oxidation is followed by subsequent complex chemistry. The decomposition of 5-ASA in solution was examined under a variety of conditions. 5-ASA decomposes most rapidly under conditions promoting oxidation and is most stable under conditions tending to inhibit oxidation. Decarboxylation was not found to be a significant degradation pathway. PMID- 1438010 TI - Solid-state stability testing of drugs by isothermal calorimetry. AB - A new technique has been developed to calculate rapidly the solid-state room temperature degradation rate of drugs and drug candidates. The technique utilizes measurements of the initial rate of heat output at several elevated temperatures by isothermal calorimetry and the degradation rate of the compound determined at a single elevated temperature by chromatography. The activation energies and degradation rates at 25 degrees C calculated by conventional methods and by isothermal calorimetry are compared and discussed. The compounds studied were phenytoin, triamterene, digoxin, tetracycline, theophylline, diltiazem, and several proprietary ICI compounds. PMID- 1438011 TI - Application of electrospray mass spectrometry (ES-MS) for the analysis of monoclonal antibody Fc subunits. PMID- 1438012 TI - Transdermal delivery of insulin to alloxan-diabetic rabbits by ultrasound exposure. PMID- 1438013 TI - Electric current-sensitive drug delivery systems using sodium alginate/polyacrylic acid composites. PMID- 1438014 TI - Ideal solubility of a solid solute: effect of heat capacity assumptions. PMID- 1438015 TI - Physical properties of fast-release nonreverting hydrochlorothiazide solid dispersions. PMID- 1438017 TI - Effect of phosphamidon and obidoxime on the QT-RR relationship of isolated rat heart. AB - We studied the effects of phosphamidon (an organophosphate compound), obidoxime (a cholinesterase reactivator), and their combination, phosphamidon/obidoxime (PD/OB) on cardiac cycle length (RR), QT interval, and on QT-RR relationship of isolated rat heart. Cardiac cycle length did not change significantly following perfusion with phosphamidon or obidoxime alone; however, following perfusion with PD/OB, RR significantly increased at high concentrations (10(-3) M) of both drugs. The QT interval lengthened by 5% following perfusion with phosphamidon, did not change following perfusion with obidoxime, and increased by 10% following perfusion with PD/OB. The QT-RR relationship without drugs was positive and linear. Following perfusion with phosphamidon alone, the slope of the relationship decreased significantly, while perfusion with obidoxime alone did not change the QT-RR relationship. Perfusion with PD/OB at low concentrations decreased the slope of the relationship; however, at the highest concentration (10(-3) M) the QT-RR relationship was inverted and became negative. Ventricular arrhythmias as premature ventricular beats, or bigeminies, were noted with increasing frequency following perfusion with increasing doses of phosphamidon. Perfusion with obidoxime did not cause arrhythmias, whereas perfusion with PD/OB caused premature ventricular beats, bigeminies, and ventricular tachycardias at high doses. We suggest that obidoxime modulates the direct effects of phosphamidon on the cardiac repolarization process. PD/OB at high concentrations invert the normal depolarization-repolarization coupling and may therefore potentiate arrhythmias. PMID- 1438016 TI - Etorphine is an opiate analgesic physicochemically suited to transdermal delivery. PMID- 1438018 TI - Inhibition of cumene hydroperoxide-induced lipid peroxidation by a novel pyridoindole antioxidant in rat liver microsomes. AB - The ability of stobadine, a novel pyridoindole antioxidant, to inhibit lipid peroxidation induced by cumene hydroperoxide was investigated in rat liver microsomes. In the micromolar range stobadine effectively inhibited lipid peroxidation as measured by the formation of thiobarbituric acid reactive products. The peroxidation-related degradation of microsomal cytochrome P-450 was prevented by stobadine in the same pattern. Another line of evidence in support of the antioxidant action of stobadine was given by its inhibition of cumene hydroperoxide-induced oxygen consumption in microsomal incubations. Inhibition of lipid peroxidation was not a function of decreased bioactivation of cumene hydroperoxide, as stobadine did not affect the rate of cytochrome P-450 dependent cleavage of cumene hydroperoxide. Neither had stobadine any effect on cytochrome P-450 peroxidase function characterized by the rate of cumene hydroperoxide dependent oxidation of TMPD, and no direct spectral interaction with microsomal cytochrome P-450 was observed in the micromolar region. We suggest that it is the ability of stobadine to scavenge alkoxyl and peroxyl radicals that is predominantly responsible for the observed antioxidant effect. PMID- 1438019 TI - Gentamicin nephrotoxicity in rat: some biochemical correlates. AB - The present work examines the effect of treatment of rats with graded doses of the aminoglycoside antibiotic gentamicin on the concentration of reduced glutathione (GSH) and diamine oxidase (DAO) activity in the kidney, and DAO activity, creatinine and magnesium (Mg) in the plasma. The animals were given the antibiotic intramuscularly in doses of 20, 40, and 80 mg/kg/day for 6 days, and were killed 24 hr after the last injection. In another experiment rats were injected intramuscularly with gentamicin at a dose of 80 mg/kg/day for 6 days and were killed 1, 7 or 14 days after the last injection, and the above parameters were measured. Gentamicin reduced the body weights of rats in a dose-dependent manner. The weight reductions were most marked on days 4, 5 and 6 of the treatment. The body weights gradually recovered on withdrawing of the drug, and by day 14, they were not significantly different from those of the controls. Gentamicin produced significant and dose-dependent decreases in the renal concentration of GSH. Seven and 14 days after withdrawing the drug, the GSH concentrations were still significantly below that of the controls. Plasma Mg concentrations were significantly decreased, and plasma creatinine concentrations significantly increased by gentamicin. These effects persisted 7 and 14 days after cessation of treatment. Plasma DAO activity was not detectable in the control or gentamicin-treated rats. In the renal cortex, the activity of the enzyme, measured 1, 7 and 14 days after the treatment, was not significantly different from that of the control. Histopathologically, the drug produced dose dependent proximal renal tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438020 TI - Pharmacokinetics in rat of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a drinking water mutagen, after a single dose. AB - The pharmacokinetics of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) was evaluated after a single oral or intravenous administration in the rats using 14C-labelled compound. Twenty to 35% of the dose was absorbed into circulation from the gastrointestinal tract as assessed from the excretion in urine. The mean elimination half-life of the radioactivity in blood (T1/2 k10) was 3.8 hr. Traces of radioactivity remained in the blood for several days. The tissues lining the gastrointestinal and urinary tract, kidneys, stomach, small intestines and urinary bladder contained the highest radioactivity. The activity declined slowest in the kidneys. Urine was the main excretion route. Seventy-seven % of the total amount excreted appeared in urine in 12 hr and 90% in 24 hr. No radioactivity was exhaled in air suggesting that elimination through respiration did not occur. After an intravenous administration of 14C-MX, the T1/2 k10, was much longer, 22.9 hr, and the total elimination half-life (T1/2 beta), 42.1 hr. The results indicate that MX is absorbed from the gastrointestinal tract to a considerable degree and it is excreted in urine very rapidly. A fraction of MX or its metabolites is retained in blood for a longer period of time. The pharmacokinetics of MX does not suggest extensive cumulation of MX in tissues after continuous exposure. PMID- 1438021 TI - Local antinociceptive and hyperalgesic effects in the formalin test after peripheral administration of adenosine analogues in mice. AB - Adenosine administered to humans has been reported to induce pain after intravenous administration. On the other hand adenosine analogues have been shown to possess antinociceptive effects after peripheral and intrathecal administration in animals. The aim of the present study was to investigate the effect of peripheral administration of adenosine agonists with different affinities for the A1 and A2 adenosine receptors on a persistent pain stimulus using the formalin test. The drugs chosen were, R-phenylisopropyl-adenosine (R PIA) with high affinity for the A1 receptor, N-ethylcarboxamide-adenosine (NECA) with almost equal affinity for the A1 and A2 receptor and 2-(2-aminoethylamino) carbonylethylphenylethylamino-adenosin e (APEC) with high affinity for the A2 receptor. The drugs were mixed with formalin and administered subcutaneously into the dorsal hind paw in mice to study the local effects. They were also injected separately from the formalin solution in different paws to evaluate the systemic effect. The total time of licking the injected paw during the first 5 min. was recorded. In high doses all compounds reduced the licking activity, but a low dose of APEC (1 microM) injected together with the formalin solution had an algesic effect. All effects were antagonized by theophylline. These results suggests that A1 adenosine receptors mediate a local peripheral antinociceptive effect and the involvement of local peripheral A2 receptors in the enhancement of the algesic response. PMID- 1438022 TI - Class III antiarrhythmic action and inotropy: effects of almokalant in acute ischaemic heart failure in dogs. AB - We studied the haemodynamic and metabolic effects of the novel class III antiarrhythmic agent almokalant (H 234/09) in acute ischaemic heart failure at a dose prolonging ventricular repolarization. In pentobarbital anaesthetized dogs, heart failure was induced by microembolization of the area supplied by the main left coronary artery until a stable left ventricular end-diastolic pressure (LVEDP) of 32 +/- 2 mmHg was achieved. Embolization depressed LV dP/dt(max), LV dP/dt(min), left ventricular systolic pressure (LVSP) and cardiac output. After intravenous infusion of almokalant (0.35 micrograms/kg) LV dP/dt(max) and LV dP/dt(min) were not significantly changed at paced cycle length of 300 msec., whereas LVSP and aortic pressure decreased both at spontaneous and paced cycle length of 300 msec. LVEDP remained unchanged. Heart rate decreased from 185 +/- 7 to 167 +/- 5 beats/min., and corrected QT-time (QTc) increased from 9.5 +/- 0.3 to 10.4 +/- 0.5 msec. Arterial concentration and net myocardial uptake of glucose, lactate and free fatty acids were not significantly influenced by almokalant. In conclusion, almokalant at a dose prolonging ventricular repolarization had no negative inotropic effect in acute ischaemic heart failure. PMID- 1438023 TI - Antithrombotic activity of a new pyrazine derivative determined by the mouse antithrombotic assay. AB - A model of pulmonary microembolization in the mouse induced by infusion of epinephrine and collagen was used to determine antithrombotic activity of indomethacin and acetylsalicylic acid and of two newly synthesized pyrazine derivatives. One of the new agents provided marked protection of mice from thrombotic challenge with epinephrine and collagen. Its effectiveness was higher than acetylsalicylic acid (especially at small doses) but smaller than that of indomethacin. The same compound was similar to acetylsalicyclic acid with respect to the inhibition of in vitro human blood platelet aggregation. The new class of pyrazine derivatives (the so-called pyrazine CH- and NH-acids) appears interesting from the view-point of the studies of platelet aggregation and may yield potential antithrombotic drugs. PMID- 1438024 TI - Evidence for cytochrome P450 2E1-mediated toxicity of N-nitrosodimethylamine in cultured perivenous hepatocytes from ethanol treated rats. AB - The involvement of cytochrome P450 in the liver toxicity of the potent carcinogen, N-nitrosodimethylamine (NDMA) was investigated in hepatocytes isolated from the periportal or perivenous region by digitonin-collagenase perfusion. Exposure of hepatocytes in culture to NDMA (0.5 or 5 mM) for up to 18 hrs caused little damage, but after 42 hr loss of cell viability became evident, and the extent of cell death was higher in perivenous cells than in periportal cells. Pretreatment of rats with ethanol caused a dramatically enhanced cell damage in perivenous cells (80%) compared to periportal cells (45%). This ethanol pretreatment caused a several-fold induction of cytochrome P450 2E1, as determined both with Western blot and as NDMA demethylase activity, and the effect was observed almost exclusively in perivenous cells. Isoniazid, an inhibitor of cytochrome P450 2E1, completely protected against NDMA toxicity. Glutathione dependent cytoprotective mechanisms and lipid peroxidation did not appear to be critical in NDMA toxicity, as evidence by lack of potentiation of toxicity by buthionine sulfoximine, an inhibitor of glutathione synthesis, and by the absence of increased lipid peroxidation. Instead, the higher expression of cytochrome P450 2E1 in the perivenous cells seems to be the main determinant for the regiospecific toxicity of NDMA, and, consequently, probably also for the associated genotoxicity. PMID- 1438025 TI - Drug metabolism in rats with cancer induced by N-nitrosodiethylamine and phenobarbital. AB - The metabolism of R- and S-warfarin in vivo and in vitro, bufuralol in vitro, and antipyrine and debrisoquine in vivo were studied in rats with cancer induced by N nitrosodiethylamine and phenobarbital treatment. Microsomal cytochrome P-450 content was greatly reduced in both healthy and cancerous parts of the livers of tumour-bearing animals. The specific activities of R-warfarin and bufuralol 1' hydroxylases were significantly elevated in rats with cancer. The activities of S warfarin hydroxylases expressed per mg microsomal protein were reduced in animals with cancer, whereas those of R-warfarin and bufuralol 1'-hydroxylases were not. The urinary excretion of R-7-hydroxywarfarin was increased and those of S-6- and S-4'-hydroxywarfarin decreased in rats with cancer. The correlations between microsomal formation and urinary excretion of all warfarin metabolites were poor, except for R-7-hydroxywarfarin. Antipyrine oxidation was increased in the cancerous state but the urinary metabolic profiles were similar in rats with cancer and in controls. The metabolism of debrisoquine was decreased in tumour bearing animals. Antipyrine metabolism did not show any correlation with either warfarin or debrisoquine metabolism, whereas several relationships were observed between warfarin and debrisoquine metabolism and between warfarin and bufuralol metabolism. PMID- 1438026 TI - Pharmacokinetics of imipenem/cilastatin sodium in children with peritonitis. AB - Fifteen children (3-12 years) with peritonitis were given imipenem/cilastatin intravenously (15 or 25 mg/kg) every six hours for 3-14 days. One day during treatment days 2-8, multiple blood and urine samples were collected from each individual over a six hour dosing interval. Twelve children completed the study. The urinary recovery of imipenem and cilastatin averaged 50-70% of the administered dose. The plasma t1/2 for imipenem averaged 55 min. while that for cilastatin was even more rapid (approximately 38 min.). Little or no accumulation of either imipenem or cilastatin was observed for this regimen in this age group of paediatric patients. Steady state conditions prevailed within 2 days of initiation of therapy. The pharmacokinetics of imipenem and cilastatin in paediatric patients 3-12 years of age appear similar to those observed for adults. PMID- 1438027 TI - GEA 857, a putative blocker of potassium conductance, enhances muscarinic agonist evoked responses: dissociation from an action on 5-HT mechanisms. AB - GEA 857 [2-(4-chlorophenyl)-1,1-dimethylethyl 2-amino-3-methylbutanoate], a structural analogue of the 5-HT uptake blocker alaproclate, was tested for its ability to modify tremor and salivation induced by muscarinic agonists (oxotremorine, arecoline) and acetylcholinesterase inhibitors (physostigmine, THA) in the male rat. These agents were employed at submaximal doses. GEA 857, similarly to alaproclate (Ogren et al. 1985a & b), produced a dose-dependent, statistically significant (in the 5-20 mg/kg dose range) enhancement of the tremor response induced by all four cholinergic stimulants. However, unlike alaproclate, GEA 857 failed to enhance salivation in a consistent manner. GEA 857 itself did not produce tremor in the absence of the muscarinic agonists or the acetylcholinesterase inhibitors. The potentiation of oxotremorine tremor by GEA 857 could be fully blocked by atropine (1 mg/kg intraperitoneally). Unlike alaproclate, GEA 857 failed to affect 5-HT uptake or 5-HT metabolism in the 10-20 mg/kg dose range. However, similarly to the action of alaproclate, the potentiating effect of GEA 857 on muscarinic responses could be explained neither by actions on serotonergic mechanisms nor by actions on muscarinic receptor mechanisms in the striatum. Evidence is presented suggesting that the ability of GEA 857 to enhance responses evoked by muscarinic agonists involves inhibitory properties of GEA 857 at certain membranal Ca(2+)-dependent K+ channels, the blockade of which can potentiate or prolong muscarinic cholinergic actions. PMID- 1438028 TI - Obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart. AB - The present study was designed to determine modulation of the direct inotropic effect of an anticholinesterase organophosphorus compound, phosphamidon, by the reactivator obidoxime. We investigated the effects of phosphamidon (n = 9), obidoxime (n = 5), and their combination (n = 5) on the mechanical and energetic indices of left ventricular function, in the isolated working rat heart model. Phosphamidon at a concentration range of 10(-6)-10(-3) M had a positive inotropic effect. Obidoxime at a concentration range of 10(-6)-10(-3) M had no significant effect on heart rate, but did have a statistically significant positive inotropic effect on end-systolic pressure, cardiac output, mean left ventricular pressure, and maximal time derivative of left ventricular pressure (dP/dtmax) (P less than 0.01). Perfusion with 10(-3) M obidoxime caused a 19% increase in left ventricular stroke work and a 31% increase in total pressure-volume area. Perfusion with phosphamidon and obidoxime at concentrations ranging from 10(-6) to 10(-3) M resulted in a more intense inotropic response than the separate drug effects. At the highest combined concentrations tested, cardiac output increased by 60%, left ventricular stroke work increased by 100%, and left ventricular total pressure volume area increased by 111% of their control values (P less than 0.001). We conclude that obidoxime augments the positive inotropic effect of phosphamidon on the isolated working rat heart. PMID- 1438029 TI - Elimination of PCB congeners via milk in rabbits administered Fenclor 64. AB - A single dose of 100 mg per kg body weight of a commercial mixture of polychlorinated biphenyls (PCB), Fenclor 64 was given intraperitoneally to pregnant rabbits. The distribution in dams and foetuses and excretion in milk was investigated for six of the congeners by quantifying them in fat from maternal adipose tissue, from whole foetuses and newborn bodies and from newborn gastric contents. The cytochrome-P-450 induction after Fenclor 64 in foetuses and suckling off-spring was followed by measuring the following hepatic mixed function oxidase (MFO) activities: p-nitroanisole-demethylase, ethoxyresorufin deethylase, ethoxycoumarin-deethylase and NADPH cytochrome-C reductase. At the 28th day of pregnancy PCB fat concentrations in foetuses were similar to those in mothers (126.4 +/- 7.1 and 152.6 +/- 28.1 micrograms/g of fat, respectively). By the 5th day of life fat concentrations in the youngs were double those of foetuses (216.81 +/- 8.12 micrograms/g) and remained high until weaning (142.2 +/ 15.5 micrograms/g at the 20th day). PCB concentrations in mothers' fat decreased during lactation (104.1 micrograms/g at the 20th day) but at the end of the experiment they were still high (95.5 micrograms/g). The cytochrome-P-450 concentration and MFO activities in young rabbits' livers from treated dams were significantly higher than controls from the 5th (P less than 0.01) to the 10th (P less than 0.01) day of life, with the exception of NADPH-cyt-C-reductase (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438030 TI - Inhalation kinetics of C6 to C10 aliphatic, aromatic and naphthenic hydrocarbons in rat after repeated exposures. AB - The toxicokinetic properties of C6 to C10 n-alkanes, aromates and naphthenes have been investigated in rats during inhalation of 100 p.p.m. of the single hydrocarbons for 3 days, 12 hr/day. The concentration of hydrocarbon was measured by head space gas chromatography in blood, brain, liver, kidneys and perirenal fat at days 1, 2 and 3, immediately after termination of exposure and 12 hr after exposure on day 3. The main conclusions drawn from the study were: a) Aromatic hydrocarbons show high concentrations in blood and low concentrations in organs. b) Naphthenic hydrocarbons show low concentrations in blood and high concentrations in organs. c) n-Alkanes show very low concentrations in blood, relatively high concentrations in brain and a high potential for accumulation in fat with repeated exposures. d) Biological concentrations of hydrocarbons within one class increase in general with increasing molecular weight, though with specific exceptions. e) Accumulation is obviously influenced by differences in metabolism and enzyme induction potential. f) Lipid solubility is not the only parameter relevant for the evaluation of hydrocarbon accumulation. PMID- 1438031 TI - Single dose pharmacokinetics of trazodone in healthy subjects. AB - Eight healthy subjects were administered trazodone-HCl orally (100 mg) with and without food and by infusion in a three way cross-over study. Unchanged trazodone was determined in serum and urine by high performance liquid chromatography after an alkaline extraction. Absorption of trazodone was irregular in fasting subjects and improved after food intake. Food intake significantly decreased the maximum serum concentrations of trazodone from 1.88 +/- 0.42 to 1.47 +/- 0.16 micrograms/ml, and increased the time for reaching maximum concentration from 1.3 +/- 0.8 hr to 2.0 +/- 1.5 hr. No differences were observed in the total amount of trazodone absorbed with or without food with bioavailability values of 65 +/- 6 and 63 +/- 4 per cent, respectively. The apparent volume of distribution and total body clearance for trazodone were estimated to 0.84 +/- 0.16 l/kg and 5.3 +/- 0.9 l/hr, respectively. The terminal elimination half-life of 7.3 +/- 0.8 hr showed no significant differences between the different ways of administration. Urinary excretion of unchanged trazodone during 26 hr was less than 0.13 per cent of the administered dose, suggesting a high degree of trazodone metabolism. Earlier statements of enterohepatic circulation of trazodone and pharmacokinetic differences between males and females were not confirmed by the present study. Due to the irregular absorption in fasting subjects, trazodone should preferably be administered after food. PMID- 1438032 TI - In vitro and in vivo evaluation of the genotoxicity of N-nitrosooxprenolol. AB - N-nitrosooxprenolol (NO-oxprenolol) might be formed in the stomach of patients taking the beta-adrenergic blocking drug, oxprenolol. This nitroso derivative has previously been shown to induce DNA damage and repair in both rat and human cultured hepatocytes. The results of the present study show that in the presence of co-cultured rat hepatocytes, 0.03 mM NO-oxprenolol produced a significant increase in the frequency of 6-thioguanine-resistant but not of ouabain-resistant mutants. No mutagenic activity was detected in the absence of metabolic activation. In mice, NO-oxprenolol (1 g/kg) increased the incidence of micronucleated cells in the liver but not in the bone marrow and the spleen. These results suggest that NO-oxprenolol, consistent with its chemical nature of nitrosamine, is biotransformed into short-lived reactive species. PMID- 1438033 TI - The effects of mercury compounds and p,p'-DDE on platelet aggregation. PMID- 1438034 TI - Reward and abuse of opiates. AB - The dependence creating properties of drugs are mediated by structures in the brain. The mesolimbic system seems to play a crucial role in the behaviourally reinforcing effects of opiates and other drugs of abuse. The significance of dopamine in opiate reinforcement is still a matter of debate, in spite of the large number of studies on this subject. Dopamine appears to be involved in conditioning processes and in drug self-administration behaviour only once it has been established. Neuropeptides, centrally active fragments of hormones, may play a role in the individual vulnerability for the development of drug dependence. Administration of a number of wellknown neuropeptides attenuates the acquisition of drug self-administration behaviour. The virtues and flaws of some widely used animal models for drug dependence are discussed. PMID- 1438035 TI - Amiloride derivatives as blockers of Na+/Ca2+ exchange: effects on mechanical and electrical function of guinea-pig myocardium. AB - The amiloride derivatives, 2',3'-benzobenzamil (BB), 3',4'-dichlorobenzamil (DCB), and 5-(N-4-chlorobenzyl)-2',4'-dimethylbenzamil (CBDB) are known as inhibitors of the Na+/Ca2+ exchange. This kind of drug action was recently suggested to be a new inotropic mechanism. In guinea-pig myocardium, we have studied the inotropic and the accompanying electrophysiological effects of the three compounds in order to assess their selectivity of action. In left atria and in papillary muscle, force of contraction increased with DCB and CBDB (atria only) at a high concentration (5 x 10(-5)-10(-4) mol/l) and after long exposure time, whereas BB produced a negative inotropic effect. In the isolated perfused Langendorff heart, the amiloride derivatives tested decreased spontaneous heart rate and force of contraction and prolonged the duration of contraction. In isolated cardiac myocytes, sodium current, calcium current and the delayed rectifier were reduced by concentrations of BB, DCB and CBDB similar to the IC50 values reported for the inhibition of the Na+/Ca2+ exchange. Our results demonstrate that the amiloride derivatives have multiple sites of action. It is concluded that more specific modulators of the Na+/Ca2+ exchange are required in order to define their contribution to the regulation of contractile activation of the heart. PMID- 1438036 TI - Effect of chloroquine on some carbohydrate metabolic pathways: contents of GHS, ascorbate and lipid peroxidation in the rat. AB - Adult male rats were treated intraperitoneally with chloroquine (5 mg/kg/day) for 9 days. A reduction in the fasting plasma glucose level by 17.6% and ascorbic acid by 45% were discernable. The treatment caused significant increase in liver lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities and reduced the activity of succinate dehydrogenase enzyme. Chloroquine also caused significant reductions in the contents of reduced glutathione and ascorbic acid in the brain and erythrocytes with a significant increase in lipid peroxidation. PMID- 1438037 TI - Mutagenicity of crude senna and senna glycosides in Salmonella typhimurium. AB - The mutagenicity of senna glycosides and extracts of senna folium and senna fructus was investigated in the Salmonella typhimurium reversion assay. Senna glycosides were inactive in all strains, except for a slight, but significant increase in mutant frequency in TA102 in the absence and presence of liver microsomes. Extracts of senna fructus and senna folium demonstrated weak activity in TA97a, TA100 and TA102 in the presence of liver microsomes, and in TA97a and TA102 in the absence of liver microsomes. A strong increase in mutant frequency (3- to 5-fold above background frequency) was observed with all extracts in TA98 in the presence of liver microsomes. This activity increased further following enzymatic hydrolysis with hesperidinase of extracts of senna fructus from one source, and could be correlated to the release of the flavonol aglycones kaempferol and quercetin. The weak or lacking activity of anthraquinone aglycones in the tested strains of Salmonella typhimurium indicates that mutagenicity can not be attributed solely to the anthraquinone content of these plant materials. The chemical nature of other mutagenic components has not been elucidated. PMID- 1438038 TI - Enhancement of morphine-induced analgesia and attenuation of morphine-induced side-effects by cocaine in rats. AB - Effect of cocaine on morphine-induced analgesia and the accompanying respiratory depression, bradycardia and hypolocomotion/sedation was studied in rats. Cardiovascular and respiratory effects were studied under pentobarbitone-induced anaesthesia. Cocaine enhanced morphine-induced analgesia in the formalin test, hot plate test and heat-induced tail withdrawal test in intact rats. However, in spinal rats a similar combination of cocaine with morphine did not produce increased latencies in the tail withdrawal test. Of the three analgesic tests used, the formalin test was the most sensitive to the enhancement, as well as to the effects of morphine or cocaine alone. Morphine at the dose of 6 mg/kg produced complete analgesia in the formalin test, significant hypolocomotion/sedation, significant bradycardia and significant decrease in the respiratory rate. At an equianalgesic dose (complete analgesia in the formalin test) of morphine (3 mg/kg)-cocaine (5 mg/kg)-combination no significant changes in heart rate, respiratory rate or locomotion(/alertness) were observed. Changes in skin blood flow determined by the laser Doppler flow method were not significant in any of the experimental conditions. The results indicate that cocaine enhances morphine-induced analgesia, mainly due to supraspinal mechanisms. In contrast, the morphine-induced bradypnoea, bradycardia and hypolocomotion/sedation are attenuated by cocaine. PMID- 1438039 TI - Changes in concentration of essential metals in kidneys and urine as indices of gentamicin nephrotoxicity in female Wistar rats. AB - Wistar rats were treated with gentamicin in single (80 mg/kg) or repeated doses (7 x 40 mg/kg) subcutaneously. Total protein as well as excretion of essential metals (Cu, Zn) with the urine were determined 24 hr after 1, 3 and 7 dosages as well as 3 and 7 days after the termination of administration. At the same time kidneys were examined histopathologically by light microscopy. Simultaneously, Cu, Zn and metallothionein levels in kidneys and liver were determined. Rats receiving gentamicin demonstrated progressive renal proximal tubular necrosis at the end of 7 days administration. At the same time elevated copper and zinc levels were observed in urine. These essential metals seem to be an indicator of gentamicin nephrotoxicity. PMID- 1438040 TI - Tri-n-butyltin increases intracellular Ca2+ in mouse thymocytes: a flow cytometric study using fluorescent dyes for membrane potential and intracellular Ca2+. AB - Effects of tri-n-butyltin (TBT) on mouse thymocytes were examined using a flow cytometer and fluorescent dyes for membrane potential and intracellular Ca2+ ([Ca2+]i). TBT at concentrations from 1 x 10(-7) M to 3 x 10(-7) M caused hyperpolarization in thymocytes during 30 min. after drug application in a time- and dose-dependent manner. Further increase in TBT concentration (to 1 x 10(-6) M) made hyperpolarization of thymocytes more profound within 5 min. after application, thereafter gradually depolarized them during the next 25 min. TBT at 3 x 10(-8) M or more (up to 1 x 10(-6) M) increased the [Ca2+]i of thymocytes. After reaching maximum [Ca2+]i at the various TBT concentrations used within 5 min. after drug application, the [Ca2+]i slightly decreased in a time-dependent manner. Effects of TBT on membrane potential and the [Ca2+]i were greatly reduced under nominal external Ca(2+)-free condition. Results suggest that TBT can promote Ca(2+)-influx to thymocytes, resulting in hyperpolarization by activation of Ca(2+)-dependent K+ current. The increase in [Ca2+]i by TBT may be related to its cytotoxic action on thymocytes. PMID- 1438041 TI - The effect of chloral hydrate and its metabolites, trichloroethanol and trichloroacetic acid, on bilirubin-albumin binding. AB - Chloral hydrate is used as a sedative in infants requiring ventilatory support. The metabolites, trichloroethanol and trichloroacetic acid, accumulate in the serum and are protein bound. The possibility that these chemicals might compete with bilirubin for albumin binding was tested using the peroxidase method and a dialysis rate method. Chloral hydrate and trichloroethanol had no effect on bilirubin-albumin binding. Trichloroacetic acid affects bilirubin-albumin binding but to a degree that would be dangerous only in infants with an unusual accumulation of this metabolite. PMID- 1438042 TI - Breathing zone concentrations of methylmethacrylate monomer during joint replacement operations. AB - By use of a methylmethacrylate (MMA) Drager tube and bellow bump, the breathing zone concentrations of MMA monomer were measured for the operating surgeon during cementation of the components of hip and knee joint prostheses. The highest recordings (50-100 p.p.m.) were encountered during cementation of the acetabular cups with conventional polymethylmethacrylate cement. Such exposure could be eliminated by the use of personal protection equipment, local punctual field suction or change to a MMA/n-decylmethacrylate/isobornylmethacrylate bone cement. PMID- 1438043 TI - Sensory irritation effects of methyl ethyl ketone and its receptor activation mechanism. AB - The burning and painful effect in nose and eyes, termed sensory irritation, of methyl ethyl ketone vapours was investigated in a mouse bioassay. Sensory irritation is mediated via the trigeminal nerves and results in a reflexively induced decrease in respiratory rate in mice. Methyl ethyl ketone was used as a model substance for ketones. At the lower exposure concentrations a partial fading (desensitization) of the response was seen. Little desensitization was seen at higher concentrations. n-Propanol, a model substance for alcohols, desensitized the receptor at all exposure levels. Preexposure to propanol did not influence the response at high methylethyl ketone concentrations. This suggests that the two substances bind to different receptive sites with different properties, if the ketone response is due to a high exposure concentration. A decrease in tidal volume was also mediated from the upper respiratory tract. The tidal volume effect is mediated by nerves different from those mediating the frequency response, as the time-response relationship, the desensitization pattern, the maximum response and the apparent dissociation constants were different for the two types of effect. Neither the location nor the perceived response related to the volume response is known. PMID- 1438044 TI - Enzyme activities in the term human placenta: in vitro effect of cadmium. AB - The effect of cadmium (Cd) as CdCl2 on some placental enzyme activities were studied after explants had been incubated with the salt for 6 or 24 hr. The results indicated that, for both incubation periods, Cd at low doses had a stimulatory effect on aryl hydrocarbon hydroxylase (AHH) (a phase I enzyme) and on quinone reductase and catecholamine-O-methyltransferase (COMT) (both phase II enzymes). This effect was dose- and time-dependent. Only the activities of AHH and COMT showed a biphasic response, (i.e., increases at the lower dose levels and decreases with the higher ones), whereas that of quinone reductase continually increased with all the dose levels of the metal administered. Glucose 6-phosphate dehydrogenase (G-6-PD) activity was found to be inhibited at all the dose levels of Cd tested, the effect also being time- and dose-dependent. In conclusion, it appears that the use of placental explants can serve as a valuable means for studying the toxic effects of certain xenobiotics, as reflected in the activity of various important enzymes. PMID- 1438045 TI - Characterisation of dopamine and serotonin uptake inhibitory effects of tetrahydroaminoacridine in rat brain. AB - The effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on uptake rates of radioactive 5-hydroxytryptamine (5-HT) and dopamine were investigated in rat diencephalon and striatal homogenates, respectively. Six and eight microM of THA were needed to inhibit 50% of dopamine and 5-HT uptake rates. Kinetic parameters, Km and Vmax, using six different concentrations of dopamine and 5-HT were estimated in the presence or absence of THA. A significant decrease in Vmax without any change in Km values was observed for both dopamine and 5-HT in the presence of THA. The results show that THA is a non-competitive uptake inhibitor of dopamine and 5-HT in the nerve terminals. The re-uptake blocking effect of THA on dopaminergic and serotonergic neurones, following THA treatment, might lead to increased levels of these monoamines in brains of Alzheimer patients and contribute in the therapeutic effects of the drug. PMID- 1438046 TI - Relationship between histamine, lipoxygenase and cyclooxygenase products in antigen-induced contraction in guinea-pig tracheal tube preparations. AB - We have used a tracheal tube preparation to study antigen-induced contraction in sensitized guinea pig airways. Treatment with both the cyclooxygenase inhibitor indomethacin and the lipoxygenase inhibitor MK-886 (L-663,536) affected this contraction in preparations with intact epithelium. Indomethacin potentiated and MK-886 inhibited part of the contraction. Leukotriene release from tracheal tubes was measured after antigen challenge, and was found to be significant in preparations with an intact epithelium. When the epithelium was removed, the histamine receptor antagonist mepyramine reduced antigen-induced contraction by 90%. Our results show that when the epithelium is absent, histamine is the most important mediator in the contraction. With the epithelium left intact, the contraction is more complex: both the cyclooxygenase and lipoxygenase pathways are involved, and our findings indicate that eicosanoid production is associated with the airway epithelium. PMID- 1438047 TI - Dose dependent induction of the microsomal monooxygenase aryl hydrocarbon hydroxylase in isolated peripheral blood monocytes: the influence of age. AB - The induction of the microsomal monooxygenase benzo(alpha)pyrene hydroxylase was investigated in isolated peripheral blood monocytes from young and old donors, after exposure to different concentrations of benzanthracene as an inducing agent. The sensitivity of the cells to the inducing stimulus was not dependent on the age of the donor. The mechanisms underlying impaired monooxygenase induction in the elderly remain to be clarified. PMID- 1438048 TI - Naloxone counteracts the fast development of tolerance to morphine in guinea-pig ileum. AB - The ability of naloxone to inhibit the fast development of tolerance to morphine was examined in the guinea-pig ileum preparation. Dose-response curves were obtained either non-cumulatively with morphine alone or cumulatively with morphine alone and in combination with different concentrations of naloxone. We present some theoretical considerations concerning the competitive interaction between agonist and antagonist on a receptor. According to these theories, it is possible to perform dose-response experiments for an agonist in combination with different concentrations of antagonist and extrapolate to the dose-response curve for agonist alone and to the dissociation constant for the antagonist. EC50 values for morphine alone obtained either non-cumulatively or by extrapolation are almost identical and are significantly lower than those obtained cumulatively. The results indicate that tolerance develops very quickly when dose response curves are obtained cumulatively with morphine alone and that low concentrations of naloxone counteract the development of tolerance. PMID- 1438049 TI - Frequency- and potential-dependency of the negative inotropic action of various dihydropyridine and non-dihydropyridine calcium antagonists. AB - Transmembrane voltage and beat frequency are important determinants of the action of several organic calcium antagonists. This is well-known for the cationic amphiphilic calcium antagonists. We intended to assess the functional impact of these phenomena in cardiac muscle with special regard to dihydropyridines. Therefore, concentration-response curves were constructed in isolated guinea-pig left atria for the negative inotropic effect of various compounds. The dihydropyridines nifedipine, racemic nitrendipine, nisoldipine, and felodipine, and the enantiomers of isradipine were investigated at different stimulation frequencies (1 Hz, 2.5 Hz, 4.5 Hz), and at different extracellular K+ concentrations (2.7 mM, 5.4 mM, 10.8 mM). These drugs were compared with the cationic amphiphilic compounds gallopamil, verapamil and diltiazem. The potency of some dihydropyridines, particularly nitrendipine, could be modulated to a remarkable extent, covering several orders of magnitude. The potential-dependency of the drugs depended on stimulus frequency and ranged from less than a half to two orders of magnitude. At 2.5 Hz, the rank order of extent of potential dependency was gallopamil greater than nitrendipine greater than diltiazem greater than verapamil = (+)-isradipine greater than (-)-isradipine greater than or equal to nisoldipine greater than or equal to felodipine = nifedipine. Based on data obtained from binding studies in intact atria and from patch-clamp measurements of calcium current blockade, a mathematical model was used which describes the observed potency changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438050 TI - Metrifonate and tacrine: a comparative study on their effect on acetylcholine dynamics in mouse brain. AB - Tetrahydroaminoacridine (THA) and metrifonate are cholinesterase inhibitors used in the treatment of Alzheimer's disease. In experimental animals they inhibit acetylcholinesterase activity and have been reported to increase levels of brain acetylcholine. This paper presents results from studies of their effect at two dose levels on the dynamics of acetylcholine in mouse brain. Metrifonate at two doses (10 and 30 mg/kg intraperitoneally), known to cause cholinesterase inhibition, had no effect on levels of acetylcholine or choline or on the rate of synthesis of acetylcholine. THA (3 mg/kg intraperitoneally) had no effect on levels of acetylcholine and choline but had a shortlasting decreasing effect on the synthesis rate of acetylcholine. THA (10 mg/kg intraperitoneally) increased levels of acetylcholine and choline and markedly decreased the synthesis rate of acetylcholine. At this dose, the animals showed severe cholinergic effects, e.g. tremor and salivation. It is suggested that a moderate cholinesterase inhibition in brain facilitates cholinergic nerve transmission which is obtained at a broader dose range for metrifonate than for THA. PMID- 1438051 TI - [The psychosocial questionnaire for pediatric oncology]. AB - A concept based on empirical data is needed for psychological support of children with cancer and their families. A number of concepts are already available, but a psychological assessment is needed, which controls the feasibility of these concepts. The psychosocial questionnaire is such an assessment, which transforms individual data into the practical psychosocial work during the entire course of cancer treatment. The diagnostical procedure includes aspects of coping with cancer, such as stress, protective and risk factors and health behavior. Data are collected before, during and after the intensive cancer treatment and in a follow up after 6 or 12 months respectively. The questionnaire has four parts. Each contains a "handbook for parents", which informs the parent in detail on each part. Thus, we enforce the potential of each parent to help him-/herself. PMID- 1438052 TI - [Involuntary childlessness: a family problem]. AB - Infertility--the inability to conceive or carry a pregnancy to live birth--will be experienced by 10% of the population of childbearing age. Infertility is known as a global problem through ages and has different cultural consequences. The infertile couples represent one neglected and silent minority group. Medical treatment have made great strides in discovering and curing infertility problems in recent years. These cures are not achieved without cost. A couple may incur tremendous physical, emotional and financial expose during the medical treatment phase. The author refers the most common psychic reactions to the emotional crisis that arise when couples experience infertility problems. She assumes that individuals or couples often will benefit from professional help and support when working through their emotional crisis. PMID- 1438053 TI - [Family therapy in divorce]. AB - A multi-generational approach to family therapy with divorce families is presented. Parents and children of such families are faced--with special problems during the phases of ambivalence, divorce and post-divorce. Their problems require varying focal points during therapeutic treatment. It focuses on arriving at a decision, finding constructive solutions for practical and emotional problems caused by the divorce ("psychic divorce" and parental cooperation concerning custody and education of the children) as well as supporting individuation and re-orientations. The main aim of therapeutic treatment is to alter the underlying pathogenic patterns of relationships and conflict-solving in order to prevent its repetition in a new partnership or in the next generation. Family therapy with divorce families is complicated to a high degree by aggressiveness, destructivity and resistance against working on central conflicts which serve to avoid feelings of anxiety, shame, guilt, anger and mourning. PMID- 1438054 TI - [Coping with individuation problems of epileptic adolescents and young adults using a multidisciplinary counseling team]. AB - Adolescence is a phase of development in which independence and a self-controlled life are being struggled for. Both the adolescents and their parents have the chance to reduce dependencies and become more and more autonomous. Epilepsy and its concomitants prevent patients from having the same lifestyle as healthy adolescents without such restrictions. Every seizure means a loss of control and is an impediment in the development towards autonomy and independence. Strategies for coping with these difficulties are dependent upon several factors: the time when the first seizures began, frequency of seizures, possible accompanying brain damage, effects of anti-epileptical drugs on behaviour, family structure and the personality of the adolescent. Highly complicated situations often arise when there is a combination of both uncleared medical questions as well as difficult psychosocial conditions. The development of more autonomy is obstructed by the fear of further seizures and this fear coincides with the process of separation from the parents at this stage of life. Epileptological and psychotherapeutic competence is needed for counseling families in these serious situations. Multidisciplinary cooperation is needed for analysing the problems of adolescents with epilepsy and their families. Only in this way can adequate strategies of intervention be developed. Two typical examples of such separation crises in adolescents with epilepsy and the supportive management of these crises through multi-disciplinary counseling shall be demonstrated. PMID- 1438055 TI - [A brief psychotherapeutic synergistic approach in child and adolescent psychiatry]. AB - The controversy between the concepts of family therapy and systemic therapy is one issue to design a synergetic concept of brief therapy in the psychiatric treatment of children and adolescents. Some principles of the radical constructivism, systemic theory an the psychology of narratives will be discussed and related to concepts of solution-oriented brief therapy. A case example demonstrates the perspectives of this approach in the ambulant psychiatric treatment. PMID- 1438056 TI - [Music therapy in a child and adolescent psychiatry department]. AB - Psychotherapy with children and adolescents makes use of methods focusing on the non-verbal area, including music therapy. The following article presents music therapy focus and techniques as practiced in an children's and adolescents' psychiatric department. A case study provides illustration, and in the final section theses on the use of music therapy in this field are presented. PMID- 1438057 TI - [Mythodrama--a group psychotherapy model for work with children and adolescents]. AB - This article discusses group psychotherapy as a possible crisis intervention technique for children and juveniles with behavioral problems at school or whose families are going through divorce, or as an intervention technique in trouble some school classes. The therapeutic group work at the Children and Juvenile Educational Counselling Centre in Bern, Switzerland, is described - "mythodrama" or the "tales, fiction and horror technique", a therapeutic approach which was developed during the last couple of years. The tale at the beginning of the article serves as an introduction and is followed by a description of the different phases of mythodrama. Finally, the main elements of this approach are summarized. PMID- 1438058 TI - Meconium peritonitis: extrusion of meconium and different sonographical appearances in relation to the stage of the disease. AB - By chance, we had the opportunity to make serial sonographic observations of the extrusion of meconium in a case of meconium peritonitis. Inflammation leads to exudative processes and production of fluid (ascites) in the fetal abdomen. Sonography at that stage of the disease may lead to a misdiagnosis such as 'fetal ascites' or 'non-immune hydrops'. After bowel perforation and extrusion of meconium, the latter appears as a solitary mass inside fetal ascites or as disseminated echogenic masses distributed subdiaphragmatically or perihepatically. Within a couple of days, in most cases the echogenicity of the masses increases. Calcifications lead to distinct shadowing. These calcifications are often the only visible signs of a previous meconium peritonitis. Serial sonograms are essential for the management of pregnancies with meconium peritonitis. If the amount of fetal ascites does not increase and no signs of cardiovascular stagnation appear, no invasive intrauterine diagnostic and therapeutic steps are required. In none out of the nine cases was a cause found. PMID- 1438059 TI - Introduction of early amniocentesis to routine prenatal diagnosis. AB - With growing awareness of the problems associated with prenatal cytogenetic diagnoses after CVS, attempts have been made to provide early amniocentesis as an alternative to CVS. Since 1990, at our clinic the gestational age limit for routine diagnostic amniocentesis has been successively lowered, first to 14 and then to 13 weeks of gestation. Thus, 811 prenatal diagnoses were performed after early amniocentesis at 13 weeks (n = 217) and at 14 weeks of gestation (n = 594). No problems were encountered. Culture failure was never observed in the early samples. Using the criteria 'number of colonies' and 'culture duration until harvest', early samples taken at 14 weeks did not differ significantly from the controls after standard amniocentesis performed at 15 and 16 weeks, respectively, whereas a minority of samples taken at 13 weeks experienced some delay in culturing. However, in each group at least 85 per cent of samples led to a diagnosis fulfilling our standard criteria of a safe diagnosis (at least 20 metaphases of at least five colonies from at least one primary culture after trypsinization) within 15 days. Some differences between the different groups can be recognized: culture duration of less than 11 days tends to be increasing after standard amniocentesis, whereas long culture duration (more than 20 days) is more often associated with early amniocentesis. However, this trend is only minimal and did not result in an increased risk of missing a diagnosis. PMID- 1438060 TI - Pseudomosaicism, true mosaicism, and maternal cell contamination in amniotic fluid processed with in situ culture and robotic harvesting. AB - This study was designed to test the usefulness of the common definitions for maternal cell contamination, true mosaicism, and pseudomosaicism for amniotic fluid specimens processed by in situ culture and robotic harvesting. We prospectively studied 4309 consecutive amniotic fluid specimens processed with these methods and found that 0.84 per cent had maternal cell contamination, 0.28 per cent had true mosaicism, and 5.4 per cent had pseudomosaicism. Although the frequencies of maternal cell contamination and true mosaicism were comparable to those in similar published studies, the frequency of pseudomosaicism was more than twice as high as that in previous reports. This finding is most likely not due to the method, but rather to a more accurate estimate of the actual frequency of pseudomosaicism in amniotic fluid cultures than reported heretofore. Follow-up clinical information was available on 72 per cent of the cases. In three cases of true mosaicism involving structural anomalies, the results of cytogenetic follow up studies on the neonates were normal. None of the pseudomosaic cases involving trisomy 8, 13, 18, or 21; triple X; or monosomy X were associated with newborns who had birth defects. PMID- 1438061 TI - The significance of choroid plexus cysts in fetuses at 18-20 weeks. An indication for amniocentesis? AB - Over a period of 25 months, all antenatal patients were offered a detailed ultrasound scan at 18-20 weeks' gestation. The lateral cerebral ventricles were scanned for the presence of choroid plexus cysts. Fifty-one patients found to have choroid plexus cysts were offered amniocentesis to exclude chromosomal abnormalities. One pregnancy, in which the only abnormality found was bilateral choroid plexus cysts, was terminated after trisomy 18 was detected on amniocentesis at 19 weeks. The other 50 pregnancies had normal fetal outcomes. The significance of the isolated finding of choroid plexus cysts is reviewed. PMID- 1438062 TI - Early second-trimester sonographic appearance of occipital haemangioma simulating encephalocele. AB - Encephalocele is the most common cause of occipital midline extracranial mass associated with hydrocephalus. A case is presented where an occipital extracranial mass associated with hydrocephalus which was detected on second trimester ultrasound examination turned out to be a haemangioma, a relatively benign lesion. We suggest that haemangioma should be considered in the differential diagnosis of extracranial masses detected prenatally. PMID- 1438063 TI - Morphological features of a case of retinoic acid embryopathy. AB - A case of retinoic acid embryopathy which was retrospectively diagnosed after delivery is presented. The affected fetus was exposed to the drug during the first month of pregnancy and second-trimester sonographic examination showed hydrocephalus and cardiac malformation. The diagnosis was made on the basis of autopsy findings and genetic enquiry. PMID- 1438064 TI - Shift of the fetal sex ratio in hCG selected pregnancies at risk for Down syndrome. PMID- 1438065 TI - Prenatal application of fluorescent in situ hybridization (FISH) for identification of a mosaic Y-chromosome marker, idic(Yp). AB - An amniocentesis was performed at 13.3 weeks' gestation for advanced maternal age. A mosaic sex chromosome pattern was found: of 50 cells examined, 34 had a 45,X karyotype. In 14 cells with a modal number of 46, a recognizable Y was substituted by a small non-fluorescent marker. C-banding identified the marker as an isodicentric in 12 cells. In two cells, the non-fluorescent marker appeared to be monocentric and looked like a non-fluorescent del (Yq), but could have been an isodicentric Y with inactivation of one of the centromeres. Two cells with a modal number of 47 showed two copies of the monocentric marker. Fluorescent in situ hybridization with an alpha satellite Y-specific centromeric probe confirmed the Y-chromosome origin of the markers and allowed for more accurate prenatal diagnostic information. PMID- 1438066 TI - Neonatal form of the hyperornithinaemia, hyperammonaemia, and homocitrullinuria (HHH) syndrome and prenatal diagnosis. PMID- 1438067 TI - Diagnosis and prenatal diagnosis of epidermolysis bullosa herpetiformis (Dowling Meara) in a mother, two affected children, and an affected fetus. AB - In utero skin biopsy was performed on a fetus at risk of an uncertain form of epidermolysis bullosa (EB). The mother had produced two affected offspring diagnosed variously as having junctional or dystrophic EB. The two offspring and the fetus were products of different fathers. The mother claimed to have no disease and on clinical examination was without blisters. Examination of the fetal skin biopsy by light and electron microscopy revealed separation of the epidermal sheet from the majority of the biopsy sample, although occasional remnants of basal cells remained associated with the basement membrane. Aggregations of keratin filaments were observed within basal cells of the detached epidermis and in the attached basal cell remnants. The diagnosis was thus suggested to be epidermolysis bullosa Dowling-Meara. Re-review of the clinical and laboratory data from the affected infants revealed a clinical and histological pattern consistent with this diagnosis. Further discussion with the mother revealed that her skin had blistered as a child and that she presently had hyperkeratotic palms and soles. This history is consistent with the autosomal dominantly inherited epidermolysis bullosa herpetiformis (Dowling-Meara). This is the first reported prenatal diagnosis of EB Dowling-Meara. The morphological criteria of intraepidermal blistering and clumped keratin filaments within basal and immediately suprabasal cells characteristic of an affected individual postnatally also identified an affected fetus. There is, however, insufficient experience to be certain that these findings will hold from region to region in the body or among all affected fetuses, and thus prenatal diagnosis on a morphological basis should still be made with caution. PMID- 1438068 TI - Fetal nuchal fluid--physiological or pathological?--In pregnancies less than 17 menstrual weeks. AB - For pregnancies less than 17 menstrual weeks, increasing amounts of nuchal fluid increase the risks of chromosome abnormalities with localized nuchal fluid, diffuse nuchal fluid, cystic hygroma, and fetal hydrops having chromosomal risks of 12, 23, 50, and 78 per cent, respectively. The ultrasound appearance of localized or diffuse nuchal fluid is not a specific discriminator, but a fluid depth of greater than or equal to 5 mm may be an indicator of increased risk of fetal chromosomal abnormalities. If the fluid depth is less than 5 mm, there is a stronger negative predictive value and negative likelihood risk of a fetal chromosome abnormality. Gestational age did not improve the fluid depth predictive value. Differentiation of physiological from pathological requires chromosome analysis, serial ultrasound evaluation, and good clinical examination as a newborn and possibly as a young child. Long-term follow-up of those cases identified with resolving nuchal fluid abnormalities is not available and is required for a complete understanding of physiological and pathological aetiologies. Genetic counselling for fetal nuchal fluid would be recommended. PMID- 1438069 TI - Prenatal diagnosis in a family with X-linked chronic granulomatous disease with the use of the polymerase chain reaction. AB - In the X-linked form of chronic granulomatous disease (X91 degrees CGD), the genetic defect is linked to the CYBB locus on the X chromosome. We studied a family with a genetic defect in this gene, consisting of a G----A substitution at the fifth base of the 5' donor splice site of intron 3. This mutation leads to skipping of exon 3 after transcription of the gene. The expectant mother was diagnosed as a carrier. Analysis of polymerase chain reaction (PCR)-amplified genomic DNA from a chorionic villus biopsy (CVB) showed the same mutation in the male fetus. After termination of the pregnancy, the diagnosis was confirmed by conventional methods. This is the first time that PCR has been used for prenatal diagnosis of CGD. PMID- 1438070 TI - Maternal serum CA 125 for aneuploidy detection in early pregnancy. AB - Maternal serum CA 125 levels were determined at 9-11 menstrual weeks for 26 cases of trisomy 13 (n = 4), trisomy 18 (n = 7), trisomy 21 (n = 15), and appropriate controls. There were no statistically significant differences between groups. PMID- 1438071 TI - The chemical composition and nutritional potential of the tribal pulse, Abrus precatorius L. AB - The boiled seeds of Abrus precatorius L. are eaten by the residents of the Andaman Islands in India. The seeds were analysed for proximate composition, total (true) protein, seed protein fractions, amino acid profile of seed proteins, minerals and certain antinutritional factors. The seed proteins are rich in most of the essential amino acids, and they are deficient only in cystine and threonine, when compared to the WHO/FAO requirement pattern. The antinutritional factors (total free phenols, tannins, trypsin inhibitor activity and haemagglutinating activity) were also investigated. PMID- 1438072 TI - Sensory evaluation of and acceptability trials on biscuits prepared from raw and malted wheat (Triticum aestivum)-Bengal gram (Cicer arietinum) mixes with or without a green leafy vegetable. AB - Biscuits were prepared by varying the amounts of the basic ingredients to arrive at the most acceptable recipe. The final recipe contained 40 g of mix, 40 g of jaggery and 20 g of ghee. Sensory evaluation of biscuits containing 5 or 10% colocasia leaf powder by composite scoring test and hedonic scale showed that the former type of biscuit was preferred over the latter. The acceptability trial conducted on 42, 3 to 6 year old children showed that biscuits from either malted mix with or without 7.5% colocasia leaf powder and raw mix were equally acceptable as shown by the analysis of variance. PMID- 1438073 TI - Microorganisms associated with natural fermentation of Prosopis africana seeds for the production of okpiye. AB - Okpiye is a food condiment prepared by the fermentation of Prosopis africana seeds. The traditional process for the production and microbiological characteristics of the condiment were investigated. During laboratory fermentation that lasted 96 h, the mesquite seeds underwent a natural fermentation that was characterised by the growth of microorganisms to 10(6) 10(8) cfu/g. Several species of bacteria especially B. subtilis, B. licheniformis, B. megaterium, Staphylococcus epidermidis and Micrococcus spp were found to be the most actively involved organisms. However, significant contributions to the microbial ecology were made by Enterobacter cloacae and Klebsiella pneumoniae. Lactobacillus spp were present in low numbers towards the end of the fermentation. The presence of Proteus and Pseudomonas spp in traditional fermented samples demonstrate the variability which may exist in the microflora of individual fermented samples. Variations in the important microbial groups show that Bacillus spp were the most prevalent species and occurred until the end of fermentation. Temperature, pH and titratable acidity varied with time and were influenced by the metabolic activities of the microorganisms. PMID- 1438074 TI - Radiation effect on ascorbic acid and riboflavin biosynthesis in germinating soybean. AB - The influence of irradiation on biosynthesis of ascorbic acid and riboflavin in germinating soybean seeds in tap and distilled water at ambient (25-35 degrees C) conditions was investigated. Ascorbic acid was not detectable in the original seeds and the initial level of riboflavin was 3.3 micrograms/g. The rate of synthesis of these vitamins increased with increasing germination time up to 72 96 hr followed by a decreasing pattern depending upon the treatment. The effect of irradiation and germination on the synthesis of these vitamins was statistically significant (P less than 0.01). Maximum amounts of ascorbic acid 16.2 and 15.0 mg/100g (fresh weight basis) were found in the 0.10 kGy sample after 72 hr of germination in tap and distilled water, respectively. However, a radiation dose of 0.20 kGy resulted in the development of maximum values of riboflavin, 30.0 and 27.0 micrograms/g (dry weight basis) on germination in tap and distilled water respectively. PMID- 1438075 TI - Bio-availability of iron from spinach (Spanicia oleracea) cultivated in soil fortified with graded levels of iron. AB - In vitro availability of iron along with ascorbic acid, oxalic acid and phosphorus contents of two varieties of spinach (Pusa Jyoti and Allgreen) cultivated in soil with different levels of added iron was determined. Addition of graded levels of iron to soil markedly increased the total iron and phosphorus contents and significantly decreased the bio-availability of iron, ascorbic acid and oxalic acid contents of spinach. Ascorbic acid and oxalic acid contents markedly exerted a positive influence while phosphorus exerted a negative influence on the bio-availability of iron. PMID- 1438076 TI - The effects of sprouting times on nutritive value of two varieties of African yam bean (Sphenostylis stenocarpa). AB - Forty-eight rats (80-125 g) were used to determine the nutritive value of two sprouted varieties of African yam bean. The cream and brown varieties were each sprouted for 36, 48 and 72 h and blended with corn in a 70:30 ratio (protein basis) to provide 1.6 g N/100 g diet for the entire study period. Sprouting for 48 h caused an increase in most of the parameters tested for both varieties. Sprouting increased natural enhancement of nutrients. PMID- 1438077 TI - Nutritional and chemical evaluation of raw seeds of Canavalia gladiata (Jacq) DC. and C. ensiformis DC: the under utilized food and fodder crops in India. AB - In India, the seeds of Canavalia gladiata and C. ensiformis have traditionally been eaten by the aborigines, but they are less popular among the civilized people. The data on the chemical composition and nutritional quality of these seeds are not readily available. The proximate composition, mineral composition, the contents of total (true) proteins, seed protein fractions, profile of seed protein amino acids and certain antinutritional factors were analysed and reported in the present study. The seeds of C. ensiformis contain more crude protein, crude lipid and minerals like Na, K, Ca, Mg, P, Fe and Mn than does C. gladiata. Both albumins and globulins together constitute the major bulk of seed proteins. In both the species of Canavalia investigated, glutamic acid, aspartic acid, isoleucine + leucine, tyrosine + phenylalanine and lysine are the major amino acids of seed proteins. The presence of certain antinutritional factors (total free phenols, tannins, lectins, L-DOPA, trypsin inhibitor activity) is also reported for both species of Canavalia. PMID- 1438078 TI - Influence of dietary soybean trypsin inhibitors and DL-ethionine on sulfur amino acid adequacy of diets for young rats. AB - Weanling male Wistar rats were fed 20% protein diets based on casein or either of two combinations of soy protein isolate and ground raw soy providing three levels of soybean trypsin inhibitors (SBTI; 0, 448 and 808 mg of trypsin inhibited per 100 g of diet respectively). DL-ethionine was included at three levels (0, 0.05% and 0.10%) with each level of SBTI. After 4, 8 and 12 weeks of ad libitum feeding, diets containing SBTI without DL-ethionine were associated with decreases in weight gain, feed efficiency, serum cholesterol and serum urea nitrogen. Higher levels of triglycerides, glutamate pyruvate transaminase (SGPT) and altered serum free amino acid levels were also found. Increased dietary levels of DL-ethionine also resulted in deficits in growth and feed efficiency, decreased serum cholesterol, increased SGPT and similar alterations in serum free amino acids. Combination of dietary SBTI with DL-ethionine resulted in even greater growth deficits and serum cholesterol decreases as well as increases in SGPT and serum triglycerides and changes in serum free amino acid levels. Methionine deficiency in the young rats fed SBTI and DL-ethionine was indicated by the changes in serum amino acids and growth deficits. Moderation of some effects over the 12 week test period suggested decreased methionine requirements in the older rats. PMID- 1438079 TI - Preparation nutritional value and acceptability of barley rabadi--an indigenous fermented food of India. AB - Rabadi fermentation of barley flour-buttermilk mixture (fresh and autoclaved) at 30, 35 and 40 degrees C for 6, 12, 18, 24 and 48 h lowered pH, enhanced titratable acidity and did not change fat and total mineral (Ca, Fe, Cu, Zn, Mn and P) content. Protein content of fermented fresh as well as autoclaved barley flour-buttermilk mixture either decreased or remained unchanges. Rabadi prepared from both types of barley flour at different temperatures and time periods was acceptable; but that which was fermented at 40 degrees C for 48 h was less acceptable in terms of taste. PMID- 1438080 TI - Changes in ascorbic acid and carbohydrate contents in tomato fruits infected with pathogens. AB - Tomato fruits Var Romer VFN, inoculated with Fusarium equiseti, F. chlamydosporium, Geotrichum candidum, Acremonium recifei, Aspergilus flavus and A. niger showed decline in ascorbic acid content with days of incubation when compared with control (uninoculated) fruits. The total soluble sugars of the inoculated fruits also showed a reduction trend as the storage period was prolonged, but slight increase was observed on the 6th day after inoculation. PMID- 1438081 TI - Control of vascular resistance in the human placenta. PMID- 1438082 TI - ATP-dependent protease in human placenta. AB - We have found that human placental mitochondria contain ATP-dependent protease in a soluble form. The molecular weight of the protease have been up to 108,000, which is the same as ATP-dependent protease in bovine adrenal cortex. Since this protease has been distributed among steroid hormone-producing tissues such as testis and adrenal cortex and ATP-dependent protease can degrade cytochrome P 450scc, a key enzyme in steroid hormone biosynthesis, we suggest that the protease may have an important role in the regulation of steroid hormone metabolism. PMID- 1438083 TI - Cellular localization of metallothionein in human term placenta. AB - Cellular localization of metallothionein (MT) in placenta may provide information on its function as a metal binding protein. Rabbit antibodies to rat liver MT cross-reacted with human MT and were used to localize MT in human term placenta by avidin-biotin peroxidase technique. Serial sections (5 microns) were cut from paraffin-embedded placentae obtained at term from five normal women and incubated with rabbit antibodies to MT. Normal rabbit serum was used as a negative control. The slides were incubated with biotinylated swine anti-rabbit IgG (linking antibody) then with avidin-biotin horseradish peroxidase complex and developed with diaminobenzidine in hydrogen peroxide (0.03 per cent) substrate. The optimum staining of MT was obtained at a 1:800 antibody dilution. MT was identified in fetal amniotic cells, syncytial trophoblasts and villous interstitial cells, and in maternal decidual cells. The presence of MT at specific cellular sites suggests that it may regulate the transplacental transport of metals such as zinc, copper and cadmium. Since the level of cadmium is lower and that of zinc and copper higher in fetal than in maternal blood, this may suggest that placental MT may restrict cadmium while enhancing zinc and copper transport. PMID- 1438084 TI - Quantitative description of the elaboration and maturation of villi from 10 weeks of gestation to term. AB - Stereological methods have been applied to a cross-sectional sample of human placentae collected at 10-41 weeks of gestation in order to provide a quantitative description of the growth and maturation of villi. Random tissue sections were analysed to derive volumes, surface areas, lengths, diameters and membrane thicknesses for villi and their fetal capillaries. Expansion of the total volume and surface area of villi can be explained by a dramatic linear growth of terminal villi which begins at about the middle of the second trimester. Growth of intermediate villi also occurs but to a more limited extent. Linear growth is accompanied by villous maturation which involves increases in the relative volume of capillaries and in villous capillarization coupled with decreases in villous diameter, capillary diameter and harmonic thickness of the villous membrane. These findings confirm that placental growth and development depend greatly on growth and maturation of terminal villi. They do not confirm sinusoidal dilation of fetal vessels as a generalized phenomenon. They also support the contention that changes in effective diffusion distances across the villous membrane have real adaptive significance. PMID- 1438085 TI - Chorionic gonadotrophin and c-myc expression in growing and growth-inhibited (intermediate) trophoblasts. AB - FEG-3 cells are a clonal line of human choriocarcinoma and resemble villous cytotrophoblasts which are the stem cells for the syncytiotrophoblast in the placenta. FEG-3 cells synthesize and secrete the alpha subunit of human chorionic gonadotrophin (hCG). Treatment of FEG-3 cells with the chemotherapeutic drug (1 microM) methotrexate (MTX) results in an increase in nuclear diameter. Cell division is blocked and a decrease in c-myc mRNA levels in observed. The effects on cell growth and c-myc mRNA expression are reversible, and cells treated with MTX for 48 h retain their proliferative potential. Assessment of placental hormone gene expression reveals that a member of the human growth hormone gene family is expressed at extremely low levels and is unaffected by MTX treatment. Alpha and beta chorionic gonadotrophin (hCG) levels are increased by MTX treatment, but levels decrease following removal of MTX. In contrast to hCG in FEG-3 cells, non-trophoblastic or ectopic production of alpha hCG in human cervical carcinoma cells is inhibited by MTX treatment. These data indicate that MTX will induce morphological and biochemical changes in FEG-3 cells. They reveal an inverse relationship between c-myc and hCG RNA expression, and suggest different mechanisms govern trophoblast versus non-trophoblast production of alpha hCG. PMID- 1438086 TI - Serial enzymatic digestion method for isolation of human placental trophoblasts. PMID- 1438087 TI - [Non steroidal anti-inflammatory agents marketed as analgesics]. PMID- 1438088 TI - [A battery of neuropsychological tests for severe dementia. An evaluation study]. AB - All patients with Alzheimer's disease progress, more or less rapidly, to a stage where they can no longer be tested with the standard neuropsychological tools. The Severe Impairment Battery (SIB) is a neuropsychological tool used to evaluate patients with severe dementia. Its maximum score is 133. The purpose of this study was to assess the reliability of a French version of SIB. Fifty-four patients with Alzheimer's disease (mean Mini Mental State examination [MMS] 10.11 +/- 6.38) entered the study. Their mean SIB score was 88.4 +/- 33.3. The patients who were most affected (MMS below 5) were distributed by SIB from 7 to 80 points. An inter-examinator study of 36 patients yielded a correlation coefficient r = 0.9957 (P = 0.0001). In an inter-test study of 17 patients the correlation coefficient was also very high (r = 0.874, P = 0.0001). Thus, SIB seems to be a reliable tool to evaluate cognitive functions in cases of severe dementia. The distribution of scores obtained by SIB in patients with an MMS below 10 demonstrates that even within groups of subjects with severe dementia distinctions can be made between their remaining capabilities. Using SIB in these patients should improve our knowledge of the natural course of the disease and give better correlation between clinical data and neuropathological and neurobiochemical tests on the one hand, and enable us to adjust to their condition the departments where these patients are treated on the other hand. PMID- 1438089 TI - [Microalbuminuria and left ventricular hypertrophy in essential arterial hypertension. A study in non-diabetic patients]. AB - To evaluate the relationship between urinary albumin excretion and left ventricular hypertrophy in essential hypertension, we studied, cross-sectionally, 64 subjects with essential hypertension and no diabetes. Urinary albumin excretion and Sokolow index correlated significantly (r = 0.483; P = 0.0001). Five subjects were positive for microalbuminuria (> 30 mg/24 h) and Sokolow index (> 35 mm); 43 were negative for both, with a concordance rate of 77 percent (chi squared test 11.1; P = 0.0009). Stepwise multivariate regression analysis indicated two independent determinants for urinary albumin excretion: Sokolow index (F = 18.29), and diastolic blood pressure (F = 12.23). The relationships between urinary albumin excretion, Sokolow index, and blood pressure were not different in the 18 subjects taking angiotensin I-converting enzyme inhibitors and in the 46 others. The close relationship between urinary albumin excretion and Sokolow index observed in this study suggests that left ventricular hypertrophy due to hypertension may account for the increased cardiovascular mortality observed in non diabetic subjects with microalbuminuria. PMID- 1438090 TI - [Mitochondrial disorder secondary to inflammation in polymyositis. Two cases]. AB - Two cases of polymyositis were followed using phosphorus nuclear magnetic resonance spectroscopy. The spectra recorded during remission were normal, but those collected from the gastrocnemius muscle during the active phase of the diseases showed an increased inorganic phosphate level or a decreased phosphocreatine content. The intracellular pH was normal. These findings may be related to an impairement in mitochondrial metabolism secondary to the inflammatory process. Moreover, the fact that the abnormalities observed disappeared after treatment suggests that phosphorus NMR spectroscopy could be used as a non-invasive method in the follow-up of polymyositis, but this must be confirmed by further studies. PMID- 1438091 TI - [Serum ferritin assay. Value and limitations]. AB - There is a good correlation between serum ferritin and the amount of iron stored in the body. Reduced levels of serum ferritin are always found in iron deficiency but elevation of serum ferritin can occur without any iron overload. According to pathological situations, red cell ferritin, glycosylated ferritin or acidic ferritin measurements are useful tests for the differential diagnosis of increased serum ferritin concentration. PMID- 1438092 TI - [Ascariasis: an unusual cause of cholangitis after choledochoduodenal anastomosis]. PMID- 1438093 TI - [Pregnancy after in vitro fertilization in a case of ejaculation deficiency (emission failure)]. PMID- 1438094 TI - [Markers of HIV and hepatis B and C viruses in programmed autotransfusion]. PMID- 1438095 TI - [Simultaneous pulmonary toxoplasmosis and primary Toxoplasma infection in AIDS]. PMID- 1438096 TI - [Spontaneously regressive hematoma of the liver after external heart massage]. PMID- 1438097 TI - [Incidentally discovered adrenal gland tumors]. PMID- 1438098 TI - [Horton's disease with normal blood sedimentation rate]. PMID- 1438099 TI - [Pathogenic role of hyperinsulinism in macroangiopathy. Epidemiological data]. AB - The hypothesis of the atherogenic role of endogenous insulin was based on a series of epidemiological studies. Several large-scale prospective studies have demonstrated that diabetes constitutes an independent risk factor for cardiovascular disease. However, neither the duration of diabetes nor the blood glucose level appear to be predictive of the incidence of a cardiovascular accident. More recent prospective studies (Finland, Australia, Paris) in non diabetic men have shown that hyperinsulinemia, while fasting or after glucose stimulation, constitutes a risk factor for fatal myocardial infarction, but they failed to show whether diabetes or the blood glucose level constituted a risk factor for the disease. Cross-sectional studies have provided similar results. Insulin resistance affects the majority of non-insulin-dependent diabetics and glucose-intolerant patients. It has also been observed in 25 percent of non-obese subjects with a normal glucose tolerance test. Associated hyperinsulinemia prevents the development of diabetes, but diabetes appears when the beta-cell function is altered and can no longer maintain this hyperinsulinemia. However, hyperinsulinemia is not devoid of cardiovascular consequences. Insulin resistance and hyperinsulinemia are also observed in patients with essential hypertension: a correlation between plasma insulin and blood pressure has been reported. These data, together with other experimental arguments, suggest that excessive endogenous insulin may participate in the rise in blood pressure. Furthermore, hypertensive patients have a high risk of coronary heart disease and this risk is not significantly decreased by anti-hypertensive treatments. This is probably related to the presence of other metabolic risk factors associated with insulin resistance: hyperinsulinemia, glucose intolerance, hypertriglyceridemia, decreased HDL cholesterol. These metabolic disorders have been grouped together under the term "syndrome X". All of these risk factors are probably also involved in the development of coronary heart disease in general population. In conclusion, epidemiological studies now suggest that insulin resistance and hyperinsulinemia increase the risk of hypertension and coronary heart disease. A great many experimental studies support this hypothesis. Lastly, it can be proposed that the increased cardiovascular risk in non-insulin-dependent diabetics is related to the fact that they belong to a larger group of insulin resistant subjects. The management of diabetes, hypertension, and all of the metabolic abnormalities would appear to be the only way of reducing the incidence of cardiovascular disease. PMID- 1438100 TI - [Arterial hypertension, hyperinsulinism and insulin resistance]. AB - The incidence of hypertension is increased in obesity, a state associated with an insulin resistance syndrome. By using an euglycemic clamp method, Ferrannini et al. demonstrated the existence of an insulin resistance state in patients with essential hypertension. However, the body mass index of the subjects studied appeared to be slightly excessive. This abnormality has not been observed in patients with secondary hypertension. Insulin resistance is probably localized to peripheral tissues such as muscles and may be associated with other cellular abnormalities. Can insulin resistance, characterized by a raised circulating insulin concentration in the presence of normal blood glucose, be responsible for certain "modifications" associated with essential hypertension? Insulin induces sodium retention and increases the aldosterone-secreting effect of angiotensin II. These effects are likely to promote a rise in blood pressure and an increase in the sensitivity of vessels to endogenous substances. Moreover, insulin is a known growth factor and is involved in lipoprotein metabolism. If insulin resistance plays an important role in the maintenance of complications of essential hypertension, it is important that the treatments used tend to correct this anomaly. Thiazide diuretics and beta-blockers aggravate insulin resistance while angiotensin converting-enzyme inhibitors correct this condition. PMID- 1438101 TI - [Theoretical aspects of the relationship between diabetic macroangiopathy and hyperinsulinism]. AB - Epidemiological and clinical data suggest a relationship between hyperinsulinism and macroangiopathy in non insulin-dependent diabetes. On the other hand, a relationship between the plasma free insulin level and macroangiopathy has not been documented in insulin-dependent diabetes. Other abnormalities in addition to hyperinsulinism and glucose intolerance are frequently associated in the presence of insulin resistance and have been grouped by Reaven under the term syndrome X: raised VLDL triglycerides, decreased HDL, and raised blood pressure. Iatrogenic hyperinsulinism appears to be an arterial risk factor, but by what mechanism may it also constitute an independent risk factor? The following theoretical aspects of a possible atherogenic role of hyperinsulinism are currently being investigated: a) insulin stimulates the proliferation and migration of smooth muscle cells either directly or via a rise in IGF1; b) insulin induces lipogenesis in the intima-media, but it has not been demonstrated that this in situ lipogenesis is atherogenic; c) insulin raises the VLDL production, decreases HDL and modifies the clearance of LDL; d) insulin increases blood pressure by stimulating both the renal reabsorption of sodium and the sympathetic nervous system; insulin resistance may also be expressed at the level of the Na-K-ATPase of vascular smooth muscle cells by decreasing the vasodilator effect of the hormone; e) lastly, insulin induces a defect of fibrinolysis mediated by an increase in the level of plasminogen activator inhibitors (PAI1). In conclusion, the combination of hyperglycemia and hyperinsulinism is probably damaging to the artery. Therapeutic intervention studies are necessary to confirm and define the role of hyperinsulinism in macroangiopathy and to answer the unresolved questions: direct or indirect role? effect of endogenous and/or exogenous hyperinsulinism? PMID- 1438102 TI - [Mode of action of benfluorex. Recent data]. AB - An increased risk of developing premature atherosclerosis is associated with stress, diabetes, obesity, and hypertension. These conditions are associated with insulin resistance, hyperglycemia, hypertriglyceridemia and hypercholesterolemia. An alternative way of interpreting insulin resistance is to consider that metabolism in this condition would be regulated to a greater extent by stress hormones and in particular by cortisol. Glucocorticoids and fatty acids (which are produced in response to stress) antagonise the actions of insulin in promoting glucose uptake and protein synthesis, in decreasing gluconeogenesis and protein catabolism, and promoting the clearance of intermediate density lipoprotein and low density lipoprotein from the circulation by the liver. They also promote the secretion of very low density lipoprotein thus producing hypertriglyceridemia and hypercholesterolemia. By contrast to this antagonism, cortisol can also facilitate the action of insulin in stimulating the storage of energy via glycogen and fatty acid synthesis and through lipoprotein lipase in adipose tissue. These effects are significant in relation to obesity and to weight gain. An increased control of metabolism by cortisol therefore produces changes in metabolism that are potentially atherogenic and it is associated with insulin resistance and the other risk factors for atherosclerosis. Benfluorex treatment improves insulin sensitivity and has antihyperglycemic and hypolipidemic effects in human beings and in experimental animals. These effects can be observed independently of weight loss, but lowering food intake also produces a metabolic benefit. Long-term treatment with benfluorex can also decrease stress responses in terms of glucocorticoid release and the stimulation of lipolysis probably by its serotoninergic control of the hypothalamic-pituitary adrenal axis. Such an action provides for an integrated treatment of the obese diabetic-hyperlipidemic syndrome. Benfluorex produces overall changes in metabolism that tend to normalise the major risk factors associated with premature atherosclerosis. This provides a potential advantage over other therapies for atherosclerosis which may ameliorate a symptom (e.g., hyperlipidemia) without treating the underlying metabolic disturbance that predisposes to atherogenesis. PMID- 1438103 TI - [Effects of chronic administration of benfluorex on the pharmacokinetics of iodine 123 labelled insulin in Zucker obese rats (fa/fa)]. AB - Zucker obese rats (fa/fa), aged 8 to 10 weeks, were treated orally by benfluorex (2 x 25 mg.kg-1, day-1) for 2 weeks and were compared with a control group of the same age treated with placebo. Benfluorex induced a break in the weight curve, a significant fall in serum triglycerides, blood glucose and plasma insulin and in the insulin content of the pancreas. Following intrajugular injection of iodine 123 labelled insulin, the liver of the treated animals bound 25 percent more insulin than the liver of control animals. Conversely, the renal clearance of insulin of the treated animals was reduced in comparison to the placebo group. These studies confirm that, in an animal model of obesity associated with insulin resistance, benfluorex exerts a marked hypolipidemic effect and improves insulin resistance. They also demonstrate an increased targeting of insulin towards hepatic receptors either due to an increase in the hepatic blood flow or to an increase in the number of hepatic receptors or to an increase in the affinity of these receptors. However, speculative considerations make this last mechanistic hypothesis somewhat improbable. PMID- 1438104 TI - [Mechanisms of hypoglycemic action of benfluorex]. AB - Benfluorex is a hypolipidemic agent with biguanide-like properties. Its action on glucose metabolism was evaluated in 6 NIDDM patients previously treated with diet alone. Before and after 1 month of benfluorex therapy (450 mg/day p.o.), an euglycemic (100 mg/dl) insulin (40 mU/m2/min) clamp was performed along with 3-3H glucose infusion and indirect calorimetry. Benfluorex did not affect body weight, while it reduced fasting plasma glucose (144 +/- 16 vs 119 +/- 8 mg/dl; P < 0.05), glycosylated hemoglobin (6.8 +/- 0.8 vs 6.4 +/- 0.4 percent) and fructosamine (2.9 +/- 0.6 vs 2.4 +/- 0.2 mmol/l; P < 0.05). Both triglycerides (2.3 +/- 0.6 vs 1.9 +/- 0.5 mmol/l) and total cholesterol (5.7 +/- 0.7 vs 5.2 +/- 0.6 mmol/l) declined. No changes occurred in plasma fatty acid, insulin, and C peptide. Basal hepatic glucose production did not change and it was completely suppressed during the clamp studies both before and after benfluorex. Basal oxidation rates of carbohydrates and lipids did not change significantly. During the insulin clamp study, insulin-mediated glucose disposal increased after benfluorex (5.7 +/- 0.3 vs 4.8 +/- 0.2 mg/kg/min; P < 0.01). Lipid oxidation was equally suppressed before and after therapy with benfluorex. Glucose oxidation was not enhanced after benfluorex while non-oxidative glucose metabolism was significantly improved (2.2 +/- 0.7 vs 3.4 +/- 0.4 mg/kg/min; P < 0.05). CONCLUSION: short-term benfluorex administration a) improves glucose and lipid control, b) improves insulin action by enhancing non-oxidative glucose metabolism, c) does not affect basal insulin secretion. The long-term effect of benfluorex treatment remains to be evaluated. PMID- 1438105 TI - [Antidiabetic efficacy of benfluorex. Clinical data]. AB - We compared the effect of 3 months of treatment by either benfluorex (B) or metformin (M) on hyperinsulinism and high blood glucose levels in overweight patients with non-insulin-dependent diabetes mellitus (NIDDM). All patients had previously complied with a low-calorie diet that had resulted in loss of more than 1.5 kg in one month, but had failed to ensure metabolic control. Weight changes under treatment were identical in both groups (B and M). Both treatments had a comparable effect on blood glucose levels, and this effect was more marked following an oral glucose load. However, a decrease in serum insulin levels and in the fasting serum insulin/fasting serum glucose ratio was seen with benfluorex only. The differences between the two treatment groups were especially marked among the subgroup of patients who responded poorly to the trial diet (fasting I/fasting G: + 1.82 under M., -3.37 under B, P interaction = 0.029). Clinical tolerance was comparable for both drugs. However, a significant rise in serum lactic acid was seen with metformin. The effect of benfluorex on hyperinsulinism in overweight patients with glucose intolerance or mildly increased fasting blood glucose levels is valuable in these high vascular risk patients. The results of this study open the way to a new approach to the treatment of diabetes which should be confirmed by a longer term study currently underway. However, already, these results encourage the evaluation of the benefit provided by benfluorex in combination with classical hypoglycemic drugs. PMID- 1438106 TI - Patient characteristics and the effect of three physician-delivered smoking interventions. AB - BACKGROUND: This paper investigates individual patient characteristics predicting differential response to each of three physician-delivered smoking interventions after 6 months. METHODS: Participants were 1,286 currently smoking patients seen by 196 medical and family practice residents in five primary care clinics affiliated with the University of Massachusetts Medical School. Of the participants, 57% were female, 92% were white, their average age was 35 years, and they smoked an average of 23 cigarettes per day. Physicians were trained to provide the following interventions: advice only (AO), a brief (< 10 min) patient centered counseling intervention (CI), and counseling plus prescription of the nicotine-containing gum Nicorette (CI+NCG). The CI+NCG condition included NCG only when appropriate and if acceptable to the patient. Patients were randomized to one of these three physician-delivered intervention conditions. RESULTS: Overall, stratified univariate analyses revealed that AO produced consistently lower cessation rates across most subgroups (generally 9-13%) but was somewhat more effective for certain groups of lighter smokers. Relative to AO, CI was somewhat more effective (about 20-24%) for less addicted smokers, for those with more previous quit attempts, and for those with fewer close associates who smoke, but generally failed to produce higher quit rates for harder core smokers or for women. CI+NCG had an overall pattern of greater effectiveness for both more addicted and less addicted smokers, with the highest absolute levels of cessation (about 27-30%) among less dependent smokers. Women in this group had cessation rates (20.6%) comparable to those of men (23.6%). Condition-stratified logistic regression analyses, controlling for a wide range of covariates, revealed associations similar to those observed in the univariate analyses: An overall logistic model in which intervention conditions were fitted as dummy variables produced the following significant main effects: sex, years smoked, contact with other smokers, symptoms, and CI+NCG condition. Significant interactions were observed for both CI and CI+NCG and smoking when feeling too ill to continue normal activities and CI+NCG and amount smoked. CONCLUSIONS: We observed significant main effects on cessation of variables related to addiction, sex, social factors, and physician counseling interventions. Specific interactions were observed between reported smoking when feeling ill and each of the counseling interventions as well as by amount smoked in the CI+NCG condition. PMID- 1438107 TI - Views of a general population on mass screening for colorectal cancer: the Burgundy Study. AB - BACKGROUND: The success of a screening program depends on a number of factors, including the validity of the test, its efficacy, its feasibility, and the rate of compliance. Thus, it is important to determine the factors influencing compliance to the screening test in order to obtain a high participation rate. METHODS: A mass screening campaign for colorectal cancer using the Hemoccult test was conducted in Burgundy, France. One year later, a questionnaire was mailed to a random sample of the population to assess the views of the general public (870 persons who had not completed the Hemoccult test, 750 persons who had a negative test, and 100 persons who had a positive test). The compliance rate of this survey was 32.2% among persons who had not completed the screening test, 88.2% among persons with a negative result, and 98.0% among persons with a positive result. RESULTS: The main reason for not participating was not wanting to know more about their health status (34.3%). Of the factors credited with encouraging persons to perform the test, the most important ones were the practitioner's explanations (55.7%) and the leaflet sent by mail (42.5%). The impact of the media campaign was weak. A small portion of the population (4.3%) said that they were very anxious while waiting for the results. Among persons with a positive screening test, only 1.2% regretted having taken it. Among those who took the test, 94.2% said they were ready to do it again; and among those who did not take it, 36.7% would accept it at a second screening. CONCLUSIONS: The data suggest that overall the Hemoccult is well accepted, that the campaign did not upset the population, and that it is worthwhile at the second screening to include those who did not participate in the first screening test. PMID- 1438108 TI - Comparison of recruitment strategies and associated disease prevalence for health promotion in rural elderly. AB - BACKGROUND: Although interest in health promotion for the elderly is increasing, the issues of recruitment into such programs and self-selection have not been well explored. While clinical studies require high participation levels and expensive recruitment, community efforts are satisfied with recruiting small numbers of volunteers from poorly defined populations. These small samples may not be representative of the populations at risk. METHODS: As part of the Rural Health Promotion Project, a Medicare demonstration, community-based recruitment methods were evaluated and participant characteristics were compared. A total of 3,884 individuals ages 65-79 were recruited in northwestern Pennsylvania, using four sequential recruitment strategies, varying in aggressiveness. The methods were: (A) mail only, (B) mail with phone recruitment follow-up, (C) mail with phone recruitment and scheduling, and (D) mail with aggressive phone recruitment and scheduling. RESULTS: Recruitment yields were Method A, 13.5%; B, 21.1%; and C, 31.6%. The most aggressive Method (D) yielded 37.0% participation. More aggressive methods (C and D) recruited more educated individuals. No other demographic or health status differences were noted. CONCLUSION: These data show that large numbers of the elderly can be recruited into a health promotion program using aggressive methods and professional interviewers. PMID- 1438109 TI - Trends in cardiovascular disease risk factors by educational level: the Stanford Five-City Project. AB - BACKGROUND: Trends in blood pressure, smoking, and cholesterol were examined from 1979-1980 through 1985-1986 in four cities in California by level of education (< high school, high school graduate, some college, college or postgraduate). METHODS: Four biennial cross-sectional surveys (n = 6,580) were conducted in two treatment and two control cities to evaluate a 6-year community health education intervention, conducted as part of the Stanford Five-City Project. RESULTS: Over the 8-year study period, men and women ages 25-74 from each educational group in the treatment cities showed significant declines in smoking prevalence and levels of blood pressure and cholesterol (with the exception of cholesterol in women). In general, declines in the least educated group (< high school) were stronger than declines in the most educated group (college or postgraduate). Similar declines occurred in each educational group in control cities. CONCLUSIONS: These results illustrate that persons from all educational levels can modify their risk for CVD and are of particular importance because of the higher prevalence of CVD risk factors among those with less education. The similarity of time trends in treatment as well as control cities suggests that the broad-based, multisource health education efforts in the United States are succeeding across the educational spectrum. PMID- 1438110 TI - Reduction of ischemic heart disease risk markers in the teenage children of heart attack patients. AB - BACKGROUND: Families of people with ischemic heart disease (IHD) are likely to share high levels of risk markers and to have similar lifestyle patterns. Teenage children in such families were the focus of a behavioral intervention program. METHODS: Families were randomly allocated to either an "early" or a "late" advice group. The late group and a third "control" group (consisting of families with no cardiovascular disease) received the intervention only after baseline measurements were repeated in all three groups at the end of 12 months. Pedigree analysis was used to compare changes across groups. RESULTS: The decrease in self reported total fat intake was greater among teenagers in the early group (mean = 3.38, SE = 1.00) than among those in the late group (mean = -0.58, SE = 1.06), as was the decrease in saturated fat intake (mean = -2.46, SE = 0.56; mean = -0.54, SE = 0.60, respectively). These differences were statistically significant (P < 0.05). There were no differences between these groups for changes in total or high-density lipoprotein cholesterol levels. There was a statistically significant difference between the change in total cholesterol levels in the control group (mean = +0.08, SE = 0.07) and that in the late group (mean = -0.14, SE = 0.11). CONCLUSIONS: The intervention program appears to have made the teenagers aware of high-fat foods, as stated fat intake was significantly lowered, but it was not successful in decreasing blood cholesterol levels. Having a parent with IHD did, however, influence the teenagers' risk-related behavior, leading to a significant reduction in blood cholesterol levels. PMID- 1438111 TI - A survey of physicians' attitudes and practices related to exercise promotion. AB - METHODS: One hundred sixty-eight physicians responded to a survey to determine their attitudes and practices related to exercise and the development of exercise prescriptions. The mean age was 45.5 +/- 10.8 years, with the majority being male (86.7%). RESULTS: The survey found that 48% of the physicians required an exercise history as part of their initial examination and 91% encouraged their patients to participate in regular exercise programs. Seventy percent of the physicians did not develop exercise prescriptions and only 23% were familiar with the American College of Sports Medicine guidelines related to the development of exercise prescriptions. Only a small number of physicians (3%) had ever taken a college-level course related to exercise physiology and the development of exercise programs. The majority (78%) felt that there was a definite need in medical school for a course related to the medical aspects of exercise. CONCLUSIONS: Results of this investigation indicate that while physicians support exercise for health promotion and rehabilitation, greater emphasis needs to be placed on physician involvement in promoting and/or prescribing exercise. PMID- 1438112 TI - Melanoma prevention: behavioral and nonbehavioral factors in sunburn among an Australian urban population. AB - BACKGROUND: To determine the independent contribution of behavioral factors to the occurrence of sunburn, sun protection behavior was assessed over 13 successive summer weekends in a total of 1,655 adults in Melbourne, Australia. METHODS: Telephone survey respondents provided detailed accounts of activities engaged in, time spent outside, and hat, clothing, and sunscreen coverage in the 4 hr around the solar midday on both weekend days, as well as skin type, sociodemographic descriptors, and degree of sunburn experienced. Independent measures of atmospheric temperature and ambient ultraviolet radiation (UVR) were added to individual records. RESULTS: The (mostly recreational) weekend sunburn in this urban sample was strongly associated with UVR, as expected. Temperature at 3 PM, sensitive skin type, youthfulness, and being male were also independently associated with sunburn. After all other predictors were controlled for, the body exposure index (which took into account time outside and hat, clothing, and sunscreen coverage) made a strong independent contribution to the explanation of sunburn (P < 0.001). CONCLUSION: It was concluded that behavior change strategies to prevent malignant melanoma of the skin are warranted. PMID- 1438113 TI - Total indoor smoking ban and smoker behavior. AB - METHODS: To assess smoking policy support and effects, 1,083 hospital employees (203 smokers) were surveyed by anonymous questionnaire 1 year after the announcement (5 months after implementation) of a new total indoor smoking ban. A second follow-up, limited to smoker respondents only, was conducted 2 years postannouncement. RESULTS: A total indoor smoking ban was supported by the vast majority of nonsmokers (89%) and ex-smokers (86%) and by nearly half of the then smoking population (45%). Consistent with previous reports, the smoking ban was associated with a significant decrease in cigarette use during work hours, particularly among moderate to heavy smokers. However, the ban did not result in increased institutional quit rates. Light smokers (< 10 cig/day), compared with heavy smokers (> or = 30 cig/day), were more likely to support the no-smoking policy and had fewer problems observing the ban. They were also less apt to report a decrease in work productivity. CONCLUSION: A total indoor smoking ban had little effect on overall institutional quit rates. Heavy smokers will, predictably, experience the greatest difficulty complying with a total indoor nonsmoking policy. PMID- 1438114 TI - Motivational characteristics of smokers at the workplace: a public health challenge. AB - BACKGROUND: Few studies have focused on the motivational characteristics of smokers who do not volunteer for cessation. This study examined the relationship between demographic and selected psychosocial factors and motivation and intention to quit smoking among employed smokers at five worksites. In addition, the distributions of smokers who are at different stages of readiness to change their smoking behavior are presented. RESULTS: Results indicate that, overall, less than 8% of employed smokers are currently ready to quit smoking and that blue-collar workers are lower in motivation than white-collar workers. Predictors of higher levels of motivation to quit smoking included higher socio-economic status, maleness, lower levels of self-reported nicotine dependence, and stronger perceptions that smoking was against the social norms of the workplace. CONCLUSION: Implications for intervention, evaluation, and policy are discussed in the context of the challenge of making a public health impact on reducing overall smoking prevalence. PMID- 1438116 TI - Public objections to environmental tobacco smoke. AB - METHODS. A randomly selected sample of Californian adults was surveyed by telephone to assess their knowledge, attitudes, and behaviors with respect to tobacco use and its control. The questions asked of this sample were whether they had recently (in the past 12 months) asked someone not to smoke in certain situations and whether they would ever consider doing such a thing. RESULTS. Results of the survey indicated that 59.1% of nonsmokers and 44.4% of smokers had asserted themselves within the past 12 months, while another 28.2 and 29.1% of the nonsmokers and smokers, respectively, indicated that they would consider asking someone not to smoke. Only 12.7% of the nonsmokers and 26.4% of the smokers indicated that they would not consider doing such a thing. Those more likely to object publicly to tobacco smoke are generally younger, are more educated, and have anti-tobacco attitudes related to either a specific health belief or social influence. PMID- 1438115 TI - Worksite smoking control activities: prevalence and related worksite characteristics from the COMMIT Study, 1990. AB - BACKGROUND: There is a pressing need for current information on worksite smoking policies and stop-smoking activities. To address these needs and identify worksite characteristics associated with such activities, a computer-assisted telephone interview was administered to 793 worksites having at least 50 employees. METHODS: Within each of the 11 COMMIT intervention communities, attempts were made to survey 30 worksites within each of three size strata: 50-99 employees, 100-249 employees, and 250+ employees. Response to the survey was good, with a screening rate of 95% and a response rate of 90%. RESULTS: Overall, 69% of responding worksites reported having written smoking policies, but only 15% banned all indoor smoking. Smaller worksites and manufacturing and wholesale/retail companies were less likely than other organizations to be smoke free or have representatives attend smoking policy workshops. Thirty-five percent of worksites reported offering smoking cessation resources or assistance for employees, but only 20% offered both cessation resources and restrictive or smoke free policies. Smaller worksites as well as wholesale/retail sales and manufacturing worksites were less likely to offer cessation resources or to participate in community wide stop-smoking events. CONCLUSION: Although the level of worksite smoking control activities was higher than that reported in earlier surveys, there is still a substantial need to increase the level of such activities, especially at smaller worksites and in manufacturing and sales organizations. PMID- 1438117 TI - Factors associated with hypertension in Nigerian civil servants. AB - BACKGROUND: Study of hypertension in segments of West African populations in transition toward Westernization may lead to better understanding of the high risk for hypertension among Westernized blacks. METHODS: Five hundred fifty-nine urban civil servants, ages 25-54, were recruited from six ministries of Bendel State, Nigeria. Blood pressure, physical measurements, urinary protein and glucose, fasting blood glucose, and demographic data were collected at the workplace. Subjects were classified as senior staff (professionals or administrators) or junior staff (non-administrators). RESULTS: Among 172 male senior staff, the age-adjusted rate of hypertension (diastolic blood pressure > or = 90 mm Hg, systolic blood pressure > or = 140 mm Hg, or on an antihypertensive medication) was 43% and occurrence rose dramatically from 21 to 63% across age groups 25-34 to 45-54, respectively. Among 266 male junior staff, the age-adjusted rate of hypertension was 23%, and occurrence did not rise with age. Logistic regression showed that body mass index (kg/m2), age, alcohol drinking, and being senior staff were all independently related to hypertension in men. On the other hand, the age-adjusted rate of hypertension in 121 women was 20% and was significantly related only to body mass index. CONCLUSION: Male urban civil servants appeared to have a risk for hypertension similar to that of U.S. black males. Age, body mass index, alcohol drinking, and other unidentified factors related to higher socioeconomic status were strong determinants of hypertension in this population. PMID- 1438118 TI - Smoking, exercise, and physical fitness. AB - BACKGROUND: Research on smoking and physical activity provides strong evidence of smoking's negative impact and physical activity's positive impact on long-term health. However, evidence regarding the association between smoking and exercise activity and the independent effects of these factors on fitness is lacking. METHODS: The associations among exercise activity, smoking behavior, and physical fitness were examined in 3,045 Navy personnel. Exercise and smoking behaviors were measured using a lifestyle survey. Physical fitness was assessed using scores on the Navy's Physical Readiness Test. Analyses of variance were conducted to examine the relationships among smoking status, exercise activity, and PRT performance. Multiple regression procedures were used to examine the relationship between smoking and physical fitness after statistically controlling for the effects of exercise. RESULTS: Smoking was associated with lower exercise levels and lower physical endurance--both cardiorespiratory (1.5-mile run) and muscular (sit-ups). After controlling for exercise activity, smoking remained significantly associated with lower physical endurance but was not related to overall body strength (lean body mass) or percentage body fat. CONCLUSION: Smoking is a detriment to physical fitness even among relatively young, fit individuals. Study findings suggest that smokers will have lower physical endurance than nonsmokers, even after differences in the average exercise levels of smokers and nonsmokers are taken into account. Cigarette smokers should be given strong encouragement to stop smoking as part of any effort to improve physical fitness. PMID- 1438119 TI - Cholesterol-related counseling by registered dietitians in northern California. AB - BACKGROUND: An estimated 40 million Americans have serum cholesterol levels that warrant medically supervised dietary intervention. Although registered dietitians are expected to play an important role in treating these patients, current treatment practices in the community are largely unknown. METHODS: A questionnaire concerning treatment practices was mailed to all 377 registered dietitians listed in the directories of the American Dietetic Association for two large California districts. Number of patients seen and length and content of dietary counseling were ascertained for three types of patients: (a) hypercholesterolemic outpatients without heart disease, (b) hypercholesterolemic outpatients who have heart disease, and (c) inpatients with myocardial infarction. RESULTS: A return rate of 59% (n = 252) was obtained for the questionnaire. A total of 44% of the registered dietitians counseled hypercholesterolemic patients in any of the categories surveyed. About 30% of the respondents counseled hypercholesterolemic outpatients without heart disease. They saw an average of 4.9 such patients a week, spent an average of 53 min in an initial session, and usually did not see the patient again in follow-up. Fewer than 10% of patients had as many as four sessions. About 27% of the respondents saw hypercholesterolemic outpatients with heart disease, averaging 3.5 such contacts per week. The reported practices were similar to those provided to noncardiac outpatients. About 22% of registered dietitians worked with hospitalized myocardial infarction patients. They spent an average of a total of 41 min over 2.5 visits with each patient. CONCLUSION: Currently, outpatient registered dietitian counseling for hypercholesterolemia appears to be limited in both the number of patients reached and the duration of the counseling. Further research into the impact of, barriers to, and efficacy of alternative delivery methods of dietary counseling is needed. PMID- 1438120 TI - Compensation strategies in sun protection behaviors by a population with nonmelanoma skin cancer. AB - BACKGROUND: Initiation of sun protection strategies can be promoted, to some extent, by educational efforts, but little is known about the merit of continuing education interventions in sustaining the desired behaviors or adding new behaviors. This prospective study clarifies the choices individuals make among the four strategies that allow them to maintain lifestyle changes. METHODS: From 1983 to 1987, the population received education about sun protection coupled with the removal of a nonmelanoma skin cancer. One year later, their choice of sun protection methods was determined. Then annually from 1985 to 1989, they received written recommendations about sun protection for a period of 2-6 years after the initial education. The maintenance, cessation, and addition to the initial sun protection behaviors were ascertained by a questionnaire, as was the intention to change. Frequency of physician visits and development of subsequent nonmelanoma skin cancer were evaluated by medical chart review for the 2-6 year phase of continued education. RESULTS: One percent of the population consisting mostly of women described ceasing tanning after 2-6 years of education. The population related a greater use of protective clothing and/or sunscreen with an SPF of 15 or greater as their reported restrictions on outdoor activities ceased. An emerging new strategy of some of the population (n = 185) was the use of sunscreens with an SPF less than 15 in association with attempts to deliberately tan and longer daily outdoor exposure. Neither frequency of physician visits nor numbers of subsequent nonmelanoma skin cancers influenced continuation or addition of sun protection behaviors. CONCLUSIONS: While the greatest reported change in behavior was temporarily associated with educational intervention linked to removal of the skin cancer, continued educational efforts may have recruited some individuals to cease tanning and encouraged others to adopt the use of protective clothing or more frequent sunscreen use as they were unable to maintain the limitations on outdoor activities. It is not possible to structure a control group restricted from mass media education; therefore, the effectiveness of specific behavior-directed education cannot be precisely determined. Nonetheless, the population described using knowledge to develop compensation sun protection strategies that preserved lifestyle. PMID- 1438121 TI - The importance of physician encouragement in breast cancer screening of older women. AB - METHODS: The relationship between physician encouragement and breast cancer screening is examined with a population-based survey of 630 women between the ages of 45 and 75. Although the women interviewed were selected on the basis of their noncompliance with mammography guidelines, nearly half had previously had at least one mammogram. RESULTS: Women reported having received more physician encouragement of breast self-examination than of mammography. Older women reported less encouragement of both screening modalities than younger women. Multivariate analyses revealed physician encouragement to be more strongly associated with screening mammography than with health status, health care utilization, attitudes, and sociodemographic characteristics: those who reported having received physician encouragement were nearly four times more likely to have ever had screening mammography. CONCLUSIONS: These and related findings are used to highlight the critical importance of physician behavior in the secondary prevention of breast cancer in older women and to identify types of patients whose needs for screening are most likely to be overlooked by physicians. PMID- 1438122 TI - [Isolated lung transplantation. I. Indications and criteria for patient selection]. PMID- 1438123 TI - [Isolated lung transplantation. II. Surgical procedure, complications and results]. PMID- 1438124 TI - [Current pattern of anthracosilicosis, its complications and correlation with other diseases (evaluation of 300 legal autopsies 1977-1988)]. AB - The spectrum of silicosis of coal miners has changed during the past decades. The life expectancy of the miners suffering from silicosis has been successfully adapted to that of the non-miners as a result of a consistent therapy. Morphologically, the processes involving large callosities have receded markedly; in their place, there has been an increased incidence of generalised focal dust emphysema that are difficult to differentiate clinically from the common chronic obstructive pulmonary diseases. Chronic bronchitis and emphysema are the most important concomitant pulmonary diseases; the incidence of tuberculosis is still enhanced and carcinomas of the lung are only rarely to be acknowledged as so called carcinomas in scar tissue. Other major diseases that coincide with silicosis are seen in p.m. statistics with customary frequency of incidence (cardiovascular diseases almost 50%, malignant tumours including those of the lung about 25%, other major diseases without respiratory organs about 10%). The main problem in expertising is to differentiate the influence of these diseases from those of silicosis; expertising must employ the legally prescribed terminology. In our own investigations based on 300 postmortem expertises, death as a result of a professionally acquired disease was acknowledged in 48% of all cases of silicosis of severity grades I to III, silicosis being the sole major disease in only half of the cases and in the other cases an essential partial contributor to the cause of death. The significance of the extended generalised dust emphysema as a special type of pneumoconioses that must be classified as grave, is emphasised in contrast to previously compiled statistics. PMID- 1438125 TI - [Public patient education in pneumology]. AB - Since February 1990 public information evenings pertaining to respiratory tract diseases have been held every month in the cities of Fellbach, Backnang and at times in Waiblingen. These sessions have met with a great show of interest from patients, doctors and the public in general, as indicated by the consistently large number of over 100 participants. This continual educational work with its accompanying measures, such as, asthma-sport, breathing exercises, and books and videos on loan, represents an effective alternative to the formally structured, patient training programs limited to a specific time period. A broad range of effectiveness is attained by engaging public media in the informative process. PMID- 1438126 TI - [The antioxidative and inflammation inhibiting properties of ambroxol]. PMID- 1438127 TI - [Pulmonary infiltrations with eosinophilia (pulmonary eosinophilia)]. AB - The pulmonary eosinophilias are characterised by radiographic lung shadows with either a peripheral blood eosinophilia of more than 450/microliter or histologic abnormalities consisting of both interstitial and intraalveolar accumulations of eosinophils and macrophages. We describe the clinical features, radiographic changes, results of bronchoscopy and follow-up studies of three women with chronic eosinophilic pneumonia of unknown aetiology. In all patients the illness resolved rapidly after treatment with corticosteroids, however one patient experienced a second episode after treatment withdrawal. We demonstrate the wide differential diagnosis of the syndrome of pulmonary eosinophilia. PMID- 1438128 TI - [Bronchiectasis with bronchopleural fistula]. AB - We report on a female patient who is now 56 years of age suffering from bronchiectasis disease. Due to the bronchopleural fistula in the middle lobe we decided to perform an operation despite left-sided bronchiectases and in spite of the obstructive airways disease. PMID- 1438129 TI - [Case report published by V. Schlegel, G. Liebetrau, W. D. Pohl, "Swine breeder's lung--a form of exogenous allergic alveolitis"]. PMID- 1438130 TI - A comparative ultrastructural and histochemical study of the metacercarial cyst walls of four species of Paragonimus (Troglotrematidae: Trematoda). AB - The metacercarial cyst walls of Paragonimus westermani, P. miyazakii, P. ohirai, and P. iloktsuenensis were examined using ultrastructural and histochemical techniques. The cyst walls of P. westermani, P. miyazakii, and P. ohirai were found to have five distinct layers, whereas the wall of P. iloktsuenensis had only two. The so-called outer cyst wall recognized on light microscopy by Miyazaki (1961) was composed of layers I-III and the so-called inner cyst wall comprised layers IV and V. The outermost layer (I) consisted of collagen fibers and probably originated from the host. Layer III detached easily from layer IV on removal of the cysts from the host tissues. Layer IV was composed of proteoglycans, and layer V consisted of protein alone. A regular hexagonal pattern in layer V appeared to be characteristic of P. westermani. Although the basic morphological patterns observed in the layers constituting the cyst walls were similar in all species examined, the thickness of each layer was apparently different. This characteristic seems to be a suitable criterion for the identification of metacercarial cysts of Paragonimus species. PMID- 1438131 TI - Electrophoretic analysis of a natural population of the Thai Paragonimus heterotremus and its genetic relationship to the three Japanese species P. miyazaki, P. ohirai and P. westermani. AB - A total of 18 enzymes (encoded by 20 loci) from Paragonimus heterotremus collected at a local area in Saraburi, Thailand, were electrophoretically compared with those from the three Japanese species P. ohirai, P. miyazaki and P. westermani using horizontal starch-gel electrophoresis. Relative genetic distances between these species were quantified. The Thai P. heterotremus was found to be most closely related to P. miyazaki and rather distantly related to P. westermani. On the other hand, among the three Japanese species, the closest relationship was observed between P. miyazaki and P. ohirai. PMID- 1438132 TI - Scanning electron microscopy of cercariae, metacercariae and adults of Pygidiopsis ardeae Koie, 1990 (Digenea, Heterophyidae). AB - The penetration apparatus of the cercaria of Pygidiopsis ardeae Koie, 1990 (Heterophyidae) is provided with five large preoral hooklets. Various types of presumably sensory structures surround the small oral aperture. Small, pointed spines protrude throughout the cercarial body. After parasite penetration and encystment in the fish intermediate host, the metacercarial tegument increases its absorptive area by developing irregular projections. Concurrently the pointed spines become scale-like and serrated. The tegumental outgrowths appear to have regressed in infective metacercariae. The external surface of mature worms removed from the intestine of domestic chickens does not differ from that of infective excysted metacercariae. Adults taken from experimentally infected chickens were identical to specimens obtained from naturally infected herons. PMID- 1438133 TI - High osmotic pressure for Pneumocystis carinii London Resin White embedding enables fine immunocytochemistry studies: I. Golgi complex and cell-wall synthesis. AB - A method for embedding Pneumocystis carinii in hydrophilic resin (London Resin White) has been developed for immunocytochemistry studies. Using high osmotic pressure (about 850 mosmol) from fixation to embedding, this method improved the preservation of the fine structure as well as the antigenicity of rabbit- and SCID mouse-derived P. carinii. Cytochemistry studies were performed using colloidal gold-conjugated lectins (concanavalin A, glycine max, Ulex europaeus) that reacted with the cytoplasmic components (endoplasmic reticulum, Golgi vesicles). Colloidal gold-conjugated streptavidin was also tested and was found to be reactive with the parasite cell wall and cytoplasmic components, which precludes its indiscriminate use in P. carinii immunocytochemistry studies. PMID- 1438134 TI - Effects of calcium channel blockers on the contractility of the filariid Acanthocheilonema viteae. AB - The role of calcium in muscle contractility was explored in the filarial nematode Acanthocheilonema viteae (Dipetalonema viteae). The parasite was slit open longitudinally and mounted in a smooth-muscle chamber that had been filled with aerated (95% N2/5% CO2) physiological solution at 37 degrees C. Nifedipine (10( 6) M) and cadmium (3 x 10(-5) M) reduced the spontaneous isotonic contractions of A. viteae, whereas verapamil (10(-5) M) and diltiazem (10(-5) M) enhanced them. The effects of nifedipine and verapamil did not appear to be due to the solvent ethanol. All of the drugs reduced the maximal contraction induced by acetylcholine (ACh, 10(-5) M), although nifedipine was the most potent. After the exposure of worm preparations to a calcium-free medium containing ethyleneglycol bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA, 10(-4) M) for 1 h, application of ACh (10(-5) M) induced a small, transient contraction. Subsequent applications of ACh in this medium had no effect. Thus, the nematode muscle contraction appears to depend on extracellular calcium. Nifedipine, diltiazem, and verapamil could act by reducing the calcium influx across the muscle membrane. PMID- 1438135 TI - Histone-DNA interactions in the chromatin of procyclic Trypanosoma brucei brucei. AB - The dissociation of histone proteins a-d from the chromatin of Trypanosoma brucei brucei procyclic culture forms was investigated by removing the proteins from the DNA by centrifugation of soluble chromatin through isokinetic sucrose gradients in the presence of NaCl. The dissociation of the T. b. brucei histones was compared with that of their higher-eukaryote counterparts H3, H2A, H2B and H4. All four histones of T. b. brucei remained bound to the DNA at 500 mM NaCl, were partially released at 750 mM NaCl and were completely dissociated from the DNA at 1 M NaCl. These interactions of histones a-d with the DNA were comparable with those of the H2 histones in the chromatin of higher eukaryotes, and histones a and d interacted with the DNA more weakly than did their higher-eukaryote counterparts H3 and H4. Substoichiometric amounts of an additional protein were recovered in the top fractions of the gradients under all dissociation conditions. This protein migrated in the H1 region of rat-liver chromatin in various gel systems. Its early release from the DNA also indicated a resemblance to histone H1. The presence of only small amounts of this protein and the relatively weak interactions of histones a and d with the DNA suggest that the mechanisms involved in chromatin compaction in T. b. brucei are different from those in higher eukaryotes. PMID- 1438136 TI - Litomosoides carinii: extraction of the microfilarial sheath components and antigenicity of the sheath fractions. AB - Microfilarial sheaths of Litomosoides carinii were isolated and extracted with 2% sodium dodecyl sulfate (SDS) and 5% 2-mercaptoethanol (2ME). Extraction with SDS alone did not alter the ultrastructure of the sheaths and yielded five polypeptides (27-67 kDa) that were not recognized by antibodies of infected hosts but reacted with antibodies to host-serum proteins. 2ME treatment caused partial solubilization of the sheaths (45% as determined by amino acid analysis), which could be further improved by combining 2ME with SDS. The remainder showed filamentous/threadlike structures on electron microscopic examination. As compared with whole sheaths, the insoluble proportion was markedly enriched in alanine and cysteine but contained less galactosamine, serine, and threonine. SDS polyacrylamide gel electrophoresis (SDS-PAGE) of 2ME/SDS-extractable components showed 12-16 bands of 14- greater than 120 kDa. A predominant component had an apparent molecular mass of 22 kDa. Two bands (42 and 120 kDa) could be stained with Coomassie blue but showed "negative" staining when gels were stained with silver. Several components (but not the 22-kDa polypeptide) bore phosphocholine epitopes. Apart from the negatively staining bands, most of the 2ME-soluble sheath components were recognized by antibodies of L. carinii-infected Mastomys coucha. Except for several polypeptides that had been unspecifically recognized by IgM, the antibody response to sheath components started at the end of the prepatent period. PMID- 1438137 TI - Studies on the developmental cycle of Trichospirura leptostoma (Nematoda: Thelaziidae). Experimental infection of the intermediate hosts Blatella germanica and Supella longipalpa and the definitive host Callithrix jacchus and development in the intermediate hosts. AB - The cockroaches Blatella germanica and Supella longipalpa can act as intermediate hosts of Trichospirura leptostoma as demonstrated by experimental infestation. The parasite developed from the embryonated egg into the infective larval stage (L3) in cockroaches within 5-6 weeks. After experimental infection of marmosets (Callithrix jacchus), eggs were first found in faecal samples (prepatency) at 8-9 weeks post-infection. Patency lasts about 2 years. Despite the presence of living adult worms in the marmosets' pancreas, no additional eggs were observed in their faeces after the patent period. PMID- 1438138 TI - Experimental infection of pigs with a Taenia species from Korea: parasitological and serological aspects. AB - Belgian Landrace piglets were experimentally infected with eggs of a Taenia sp. of Korean origin. At autopsy, metacestodes were present only in the livers. The proportion of degenerated metacestodes increased from 12%-39% at 5 weeks to 94% 100% at 10 weeks after infection. A sandwich enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies raised against the excretory-secretory products of T. saginata metacestodes detected circulating antigen in the sera of the pigs at 1 week post-infection. A good correlation was found between the presence of viable metacestodes and the detection of circulating antigen; the latter disappeared as the metacestodes died off. However, the antibodies were detected only after 3 weeks of infection and onwards until the necropsy of the pigs. PMID- 1438139 TI - Ultrastructure of sperm and spermatogenesis of Rugogaster hydrolagi, Schell 1973 (Platyhelminthes, Trematoda, Aspidogastrea, Rugogastridae). AB - Mature sperm of Rugogaster hydrolagi exhibit the structure typical of Trematoda, with 2 axonemes of the 9+ "1" pattern being incorporated into the sperm body, dorsal and ventral microtubules occurring in the principal region that contains the nucleus and mitochondrion, and a complete row of peripheral microtubules lying in the proximal region surrounding the two axonemes. During spermiogenesis, a zone of differentiation develops that comprises a row of microtubules along the cell membrane and an adjacent dense region along the nuclear membrane. The intercentriolar body and centrioles appear between the microtubules and the nucleus. Free flagella with striated rootlets grow out in opposite directions, the cell membrane protrudes and lengthens into a median cytoplasmic process (MCP), the nucleus and mitochondrion move into the MCP and the flagella rotate and eventually fuse with the process. A dense region develops in the spermatid shaft some distance from the proximal end, but it is not present in the mature sperm. The spermatid elongates and is eventually pinched off from the residual body at the level of the arching membranes after the rootlets and intercentriolar body have disappeared. Thus, spermatogenesis and sperm in the aspidogastrean Rugogaster hydrolagi correspond to those in digenean Trematoda. PMID- 1438140 TI - Interaction between Ascaris suum and Pasteurella multocida in the lungs of mice. AB - In an experiment including 8 groups of 15 mice, the effect of migrating Ascaris suum larvae in the lungs on the establishment and pathogenicity of aerosol exposure to Pasteurella multocida was investigated. Following aerosol exposure to P. multocida, mice with migrating A. suum in their lungs developed more severe pneumonia and septicaemia than did parasite-free mice. The parasite-induced effect on bacterial pathogenicity was more marked for a non-toxin-producing P. multocida as compared with a toxin-producing strain of P. multocida, possibly due to the higher spontaneous pathogenicity of the non-toxigenic strain of P. multocida. The present results should encourage controlled experiments on possible interactions between A. suum and various airborne microbial infections in pigs. PMID- 1438141 TI - Detection and quantitation of cell-surface sugar receptor(s) of Leishmania donovani by application of neoglycoenzymes. AB - Promastigote culture forms of the log growth phase of Leishmania donovani stock LRC L 51 were investigated for expression of cell-surface carbohydrate-binding sites using 15 types of a chemically glycosylated enzyme termed neoglycoenzyme. Carbohydrate conjugation and coupling yield were kept constant to ensure that the type of carbohydrate moiety was the only variable feature of the applied tools. Para-aminophenyl derivatives of the following carbohydrate residues were used for the glycosylation of beta-galactosidase from Escherichia coli: beta-D-lactose, beta-D-thiogalactose, alpha-D-mannose, alpha-L-rhamnose, alpha-D-N acetylgalactosamine, beta-D-N-acetylgalactosamine, beta-D-N-acetylglucosamine, the alpha- and beta-glucosides maltose and cellobiose, beta-D-xylose, alpha-D mannose-6-phosphate, the alpha-galactoside melibiose, alpha-L-fucose, and beta-D glucuronic acid as well as sialic acid. Only melibiose, fucose, and glucuronic acid showed no binding affinity for the cultured flagellates; this served as an internal control reaction to exclude any binding to the linker group. This result demonstrates that many but not all sugar types can be recognized by appropriate receptor structure(s) on the surface of the promastigote Leishmania. Transformation of the binding data for neoglycoenzymes exposing lactose, mannose, rhamnose, and N-acetylated hexose residues, which was carried out to obtain the dissociation constants and to estimate the number of binding sites at saturation, revealed KD values of around 100 mM and around 10(4) binding sites for the polyvalent ligands. PMID- 1438142 TI - Electrophoretic evidence of a hybrid origin for tetraploid Paragonimus westermani discovered in northeastern China. PMID- 1438143 TI - Phosphorylation of Toxoplasma gondii major surface antigens. AB - The phosphorylation of the major surface proteins of Toxoplasma gondii tachyzoites was investigated. Metabolic labeling of intracellular tachyzoites with [32P]-orthophosphate followed by immunoprecipitation with specific monoclonal antibodies showed that all five major surface proteins were labeled as expected for GPI-anchored proteins. More detailed analysis of the phosphorylated sites revealed that surface proteins P30 and P22 contained phosphoserine residues in addition to the phosphorylated molecules that are presumably localized in the GPI-membrane anchors. PMID- 1438144 TI - A cytochemical study of the interaction between Tritrichomonas foetus and mouse macrophages. AB - Light and electron microscopy were used to analyse the process of interaction of normal and antibody-coated Tritrichomonas foetus with resident and activated mouse peritoneal macrophages. Activated macrophages ingest more parasites than do resident macrophages. Previous incubation of the parasites in the presence of sub agglutinating concentrations of a polyclonal anti-T. foetus antibody significantly increased their ingestion by the macrophages. Adherence of the parasites to the surface of activated macrophages triggers the respiratory oxidative burst as revealed by reduction of nitroblue tetrazolium. This process was more evident in antibody-coated parasites. Transmission electron microscopy showed the presence of reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H]-oxidase in the portions of the macrophage plasma membrane that were in contact with the parasites as well as in the phagocytic vacuoles. Fusion of macrophage lysosomes with parasite-containing phagocytic vacuoles was observed in macrophages labeled with Lucifer yellow and gold-labeled peroxidase as well as by localisation of acid phosphatase. PMID- 1438145 TI - Changes in atrial natriuretic factor and plasma renin activity in dogs infected with Trypanosoma brucei. AB - When beagle dogs were infected with Trypanosoma brucei, a marked reduction in the plasma concentration of atrial natriuretic factor (ANF) occurred in the terminal stage of the disease during weeks 3 and 4. At the same time there was an increase in plasma renin activity (PRA) after infection. Ultrastructural studies of the atria of these dogs demonstrated a reduction in ANF granules. The changes in ANF and PRA occurred in association with severe pancarditis and the development of heart failure. By impairing the ability of the heart and kidneys to regulate blood volume, the alterations in ANF and PRA could be involved in the pathogenesis of heart failure in T. brucei-infected dogs. PMID- 1438146 TI - Sarcocystis jorrini sp. nov. from the fallow deer Cervus dama. AB - Sarcocystis jorrini sp. nov. isolated from the muscle of naturally infected fallow deer (Cervus dama) from the Donana National Park (Spain) is described by light and electron microscopy. Sarcocysts were macroscopic (2.7 x 1.4 mm) and were found in all striated muscle, including that of the esophagus and the heart. As visualized by light microscopy, the cyst walls were formed by mammilated protrusions surrounded by a coating of connective tissue measuring 10-35 mm in thickness. Electron microscopy revealed that the parasitophorous vacuole was serrated in appearance, with numerous pinocytic vesicles running along its whole length. Villar protrusions were of varying shape and were square, rectangular, or linguiform in cross section. The core of the villi contained small dense granules and microfilaments, which were more abundant in peripheral areas. Ground substance contained larger dense granules clustered around the base of villi. The sarcocyst was surrounded by a secondary cyst wall composed of collagen fibrils and fibrocytes. S. jorrini is the first macroscopically visible sarcocyst of the genus Cervus reported to have a secondary cyst wall. PMID- 1438147 TI - Plasmodium falciparum and P. berghei: detection of sporozoites and the circumsporozoite proteins in the saliva of Anopheles stephensi mosquitoes. AB - Sporozoites and free circumsporozoite (CS) protein were stained immunoenzymatically in 1-min saliva samples collected from Anopheles stephensi mosquitoes infected with either Plasmodium berghei or P. falciparum. The number of sporozoites in 1-min saliva-streak samples significantly increased as the salivary gland index rose from 3+ to 4+. For P. berghei-infected mosquitoes from which saliva had been collected before 30 days postfeed, the median sporozoite counts for 3+ and 4+ gland indexes were 4.5 and 116, respectively. For P. falciparum-infected mosquitoes, the median counts obtained in two experiments were 4.5 and 14.5 (3+) and 97 and 107 (4+), respectively. The frequency of sporozoite detection in the saliva of mosquitoes containing < 100 salivary-gland sporozoites was low (0.1), whereas that in the saliva of mosquitoes with > 100 sporozoites was high (0.96). In highly infected 4+ P. berghei-infected mosquitoes from which saliva had been collected after 30 days postinfection, both the volume of saliva collected and the median number of sporozoites recovered decreased significantly. PMID- 1438148 TI - Scanning and transmission electron microscopy of host cell pathology associated with penetration by Eimeria papillata sporozoites. AB - Scanning and electron microscopy was used to study the pathogenesis that occurred in mouse epithelial cells that had been penetrated by Eimeria papillata sporozoites. Optimal penetration of parasites injected into nonligated and ligated mouse intestine was found to occur at 4-15 min post-inoculation. During initial penetration, the parasite caused disruption of the microvilli of the intestinal cells, which led to detachment of the microvilli from the plasma membrane of the penetrated cell. Host cells penetrated by the parasite showed extensive destruction of the internal cellular organization together with blebbing of host-cell cytoplasm and release of internal organelles such as mitochondria. Ultimately, the penetrated cells completely broke down, leaving vacuolated areas next to ultrastructurally normal epithelial cells. PMID- 1438149 TI - Immunocytochemical localization of a cysteine protease in adult worms of the liver fluke Fasciola sp. AB - The intracellular localization of a cysteine protease from Fasciola sp. that hydrolyzes host hemoglobin as a nutritional source was examined by light and electron microscopic immunocytochemistry using a monoclonal antibody specific to the enzyme. Immunoperoxidase staining was predominantly restricted to large numbers of granules in the parasite intestinal epithelial cells and to host erythrocytes present in the intestinal lumens. In immunogold electron microscopy, the gold particles were consistently deposited on the electron-dense secretory granules in intestinal epithelial cells and on the intestinal contents. These findings suggest that the Fasciola cysteine protease in the secretory granules is secreted as a digestive enzyme into the intestinal lumen, where it may play an important role in the extracellular degradation of host proteins, including hemoglobin. PMID- 1438150 TI - Neuroanatomy of Cysticercus cellulosae (Cestoda) as revealed by acetylcholinesterase and nonspecific esterase histochemistry. AB - The nervous system of Cysticercus cellulosae, the metacestode stage of the tapeworm Taenia solium, was delineated using histochemical methods for the localization of the enzyme markers; nonspecific esterase and acetylcholinesterase. The main features of the nervous system include a pair of cerebral ganglia, a circumcerebral nerve ring, a rostellar nerve ring, and anterior and posterior nerves and their branches. The posterior nerves form a subtegumental network in the strobila and the bladder wall. A nerve network around excretory tubules could also be demonstrated, suggesting neuronal control of excretion in the metacestode. No sheath was observed around the nervous system. The morphological features described suggest "cephalization" of the nervous system in this parasite. PMID- 1438151 TI - Summer-arrested development of abomasal trichostrongylids in Awassi sheep in semi arid areas of north-west Syria. AB - Inhibition in trichostrongylids was studied in Awassi sheep in North-west Syria, which has cold winters and hot summers. On six occasions during a 1-year period, five ewes with natural helminth infections were slaughtered after being held in pens for 3 weeks. The percentage of inhibited larvae was lowest in January (6%); it increased during the spring to 76.7% in April and to 84.6% in June and then decreased during the autumn (57.1% in September, 26.1% in December). Inhibition occurred mainly during the early fourth stage in mucosa but was also observed during the late fourth stage in digesta. Teladorsagia circumcincta was the main species involved, but it seemed that this phenomenon also occurred in Marshallagia marshalli. PMID- 1438152 TI - Transmission electron microscopy of sensory receptors of Echinostoma revolutum (Froelich 1802) cercaria (Digenea: Echinostomatidae). AB - Nonciliate, uniciliate, and multiciliate receptors were shown by transmission electron microscopy to occur in the body tegument of Echinostoma revolutum (Froelich 1802) cercariae. Detailed studies revealed three types of nonciliate, four types of uniciliate, and one type of multiciliate sensory endings. Most receptors were singly distributed. Only a few of them formed paired receptor complexes in three regions of the cercarial body. These receptor complexes were found to possess nonciliate, uniciliate, and multiciliate sensory endings. PMID- 1438153 TI - In vitro culture of the strobilar stage of Echinococcus granulosus of sheep and donkey origin from Jordan. AB - Protoscolices of Echinococcus granulosus isolated from hydatid cysts of sheep and donkeys in Jordan were cultured in vitro using a modified diphasic culture system. Protoscolices from these two sources manifested differences in the mode of development, evagination and growth rates. Protoscolices isolated from sheep cysts grew in vitro in the polyzoic direction up to the three- to four-segmented mature worms, reaching a length of 2.9 mm. In contrast, donkey protoscolices failed to develop beyond the early stages, even after 67 days of culturing. On prolonged culturing, few worms of donkey origin reached the banding and segmentation stages, attaining a maximal length of 1.6 mm at periods ranging between 81 and 114 days of culturing. None of these segmented worms showed genital differentiation or analgen. The evagination and growth rates of protoscolices isolated from donkey liver cysts were compared with those obtained from sheep liver or lung cysts. The most significant difference in these rates occurred at the commencement of the segmentation stage. Differences in the development, growth and evagination rates observed between the donkey and sheep forms may reflect the strain variation of E. granulosus in this country. PMID- 1438154 TI - Detection of oocysts of Cryptosporidium in several species of monkeys and in one prosimian species at the Barcelona Zoo. PMID- 1438155 TI - Host specificity of Giardia muris isolates from mouse and golden hamster. AB - One isolate of Giardia muris from a naturally infected laboratory mouse (Mus musculus) and one from a naturally infected golden hamster (Mesocricetus auratus) were passaged three times by the inoculation of ten cysts (the minimal infectious dose) into barrier-maintained homologous hosts. Both of the resultant isolates were tested for infectivity by intragastric inoculation of 3-5 x 10(5) cysts into 40 mice (2 inbred strains), 40 rats (2 inbred strains), and 19 golden hamsters (1 outbred strain). Rats were not susceptible to infection with either isolate. Mice and golden hamsters did develop infections following their inoculation with the heterologous isolates. The mean intensity of heterologous infections with the hamster isolates was significantly lower than that of homologous infections. The mouse isolate induced a higher mean intensity of infection in hamsters as compared with homologous recipients. The mean intensity of infections induced by both isolates was greater in male hamsters than in females. PMID- 1438156 TI - Epsilon-(gamma-glutamyl)lysine cross-links in Litomosoides carinii microfilarial sheaths. PMID- 1438157 TI - The solution structure of echistatin: evidence for disulphide bond rearrangement in homologous snake toxins. AB - The solution structure of the fibrinogen antagonist, echistatin, has been determined by a combination of NMR and simulated annealing methods. While the structure of the disulphide-linked core is well-defined by the NMR data, the N- and C-termini and the loop bearing the RGD sequence (which is responsible for the fibrinogen antagonist properties) are poorly defined. The pattern of disulphide bridges, which could not be determined by classical methods, was predicted by a statistical analysis of the simulated annealing structures. This pattern is distinct from that for the homologous protein kistrin, leading to the novel suggestion that homologous proteins possess non-conserved patterns of disulphide bridges. PMID- 1438158 TI - Construction of a dictionary of sequence motifs that characterize groups of related proteins. AB - An automatic procedure is proposed to identify, from the protein sequence database, conserved amino acid patterns (or sequence motifs) that are exclusive to a group of functionally related proteins. This procedure is applied to the PIR database and a dictionary of sequence motifs that relate to specific superfamilies constructed. The motifs have a practical relevance in identifying the membership of specific superfamilies without the need to perform sequence database searches in 20% of newly determined sequences. The sequence motifs identified represent functionally important sites on protein molecules. When multiple blocks exist in a single motif they are often close together in the 3-D structure. Furthermore, occasionally these motif blocks were found to be split by introns when the correlation with exon structures was examined. PMID- 1438159 TI - Ligand requirements for Ca2+ binding to EGF-like domains. AB - Site-specific mutagenesis studies of the first epidermal growth factor-like (EGF like) domain of human clotting factor IX suggest that the calcium-binding site present in this domain (dissociation constant Kd = 1.8 mM at pH 7.5 and ionic strength I = 0.15) involved the carboxylate residues Asp47, Asp49 and Asp64. To further characterize the ligands required for calcium binding to EGF-like domains, two new mutations, Asp47----Asn and Asp49----Asn, were introduced into the domain by peptide synthesis. 1H-NMR spectroscopy was used to obtain the dissociation constants for calcium binding to these mutations. Calcium binding to the Asp49----Asn modified domain is only mildly affected (Kd = 6 mM, I = 0.15), whereas binding to the Asp47----Asn modified domain is severely reduced (Kd = 42 mM, I = 0.15). From these data, it is proposed that the anionic oxygen atoms of the side chains of residues 47 and 64 are essential for calcium binding, whereas the side chain ligand for calcium at residue 49 can be a carboxyamide oxygen. As a control, the introduction of the modification Glu78----Asp in a region of the domain not believed to be involved in calcium binding had very little effect on the Kd for calcium (Kd = 2.6 mM, I = 0.15). Finally, the effect of an Asp47--- Gly substitution found in the natural haemophilia B mutant, factor IXAlabama, was investigated. This peptide has a markedly reduced affinity for calcium (Kd = 37 mM, I = 0.15), suggesting that the defect in factor IXAlabama is due to impaired calcium binding to its first EGF-like domain. PMID- 1438160 TI - Comparison of the modelled thyroxine binding site in TBG with the experimentally determined site in transthyretin. AB - The structure of cleaved thyroxine-binding globulin (TBG) has been modelled on the crystal structure of cleaved alpha 1-antitrypsin (a member of the serine proteinase inhibitor, serpin, superfamily) based on the high sequence homology exhibited by the two proteins. Particular attention was paid to the identification and modelled characteristics of the thyroxine binding site. The primary aim of the study was to compare the site qualitatively with the crystallographically determined binding site of transthyretin, the other major transporter of thyroxine, in an attempt to explain the higher binding affinity of the site compared with the known thyroxine binding site in transthyretin (10(10) versus 10(8) M-1). The proposed binding site shares some similar characteristics with the transthyretin binding site but also includes a cluster of aromatic residues which are entirely absent in transthyretin. It is proposed that this might account for the substantial difference in binding affinities. PMID- 1438161 TI - Effects of signal peptide changes on the secretion of bovine somatotropin (bST) from Escherichia coli. AB - Bovine somatotropin (bST) was secreted from Escherichia coli at moderate levels of 1-2 micrograms/ml/OD using expression vectors in which the bST gene was fused to the lamB secretion signal. To study the secretion properties of bST in E.coli further, two approaches for modifying the secretion signal were employed. In the first case, fusion proteins were constructed with six alternative bacterial secretion signals: three from E.coli proteins (HisJ, MalE and OmpA), two from bacteriophage proteins (M13 coat protein and PA-2 Lc) and one from the chitinase A protein of Serratia marcescens. The results, as monitored by Western blot analysis of both total cell protein and the periplasmic fraction, showed that these changes in the secretion signal did not significantly affect the secretion properties of bST. In the second approach, a library of random mutations was created in the lamB secretion signal and 200 independent clones were screened. The level of secreted bST was determined by growing individual clones in duplicate in microtiter wells, inducing protein expression and measuring the bST released by osmotic shock using a particle concentration fluorescent immunoassay. The secretion properties of several novel variants in the LamB signal peptide are presented. PMID- 1438162 TI - Improved insulin stability through amino acid substitution. AB - Insulin analogs designed to decrease self-association and increase absorption rates from subcutaneous tissue were found to have altered stability. Replacement of HB10 with aspartic acid increased stability while substitutions at B28 and/or B29 were either comparable to insulin or had decreased stability. The principal chemical degradation product of accelerated storage conditions was a disulfide linked multimer that was formed through a disulfide interchange reaction which resulted from beta-elimination of the disulfides. The maintenance of the native state of insulin was shown to be important in protecting the disulfides from reduction by dithiothreitol and implicitly from the disulfide interchange reaction that occurs during storage. To understand how these amino acid changes alter chemical stability, the intramolecular conformational equilibria of each analog was assessed by equilibrium denaturation. The Gibbs free energy of unfolding was compared with the chemical stability during storage for over 20 analogs. A significant positive correlation (R2 = 0.8 and P less than 0.0005) exists between the conformational stability and chemical stability of these analogs, indicating that the chemical stability of insulin's disulfides is under the thermodynamic control of the conformational equilibria. PMID- 1438163 TI - Altering the association properties of insulin by amino acid replacement. AB - The importance of ProB28 and LysB29 on the self-association of insulin was established by systematically truncating the C terminus of the B chain. The relationship between structure and association was further explored by making numerous amino acid replacements at B28 and B29. Association was studied by circular dichroism, size-exclusion chromatography and ultracentrifugation. Our results show that the location of a prolyl residue at B28 is critical for high affinity self-association. Removal of ProB28 in a series of C-terminal truncated insulins, or amino acid replacement of ProB28, greatly reduced association. The largest disruption to association was achieved by replacing LysB29 with Pro and varying the amino acid at B28. Several of the analogs were predominantly monomers in solutions up to 3 mg/ml. These amino acid substitutions decreased association by primarily disrupting the formation of dimers. Such amino acid substitutions also substantially reduced the Zn-induced insulin hexamer formation. The formation of monomeric insulins through amino acid replacements was accompanied by conformational changes that may be the cause for decreased association. It is demonstrated that self-association of insulin can be drastically altered by substitution of one or two key amino acids. PMID- 1438164 TI - Selection of a thermostable variant of chloramphenicol acetyltransferase (Cat 86). AB - The moderate thermophile Bacillus stearothermophilus was used as a host in which to detect more thermostable variants of the B.pumilus chloramphenicol acetyltransferase (Cat-86) protein. Seventeen mutants were isolated and detected by their ability to grow in the presence of chloramphenicol at a previously restrictive temperature (58 degrees C). The genes encoding these proteins were sequenced; all 17 mutants carried the same C to T transition that conferred an amino acid substitution of alanine by valine at position 203 of the protein sequence. The wild-type and one mutant Cat-86 protein were purified to homogeneity using affinity chromatography, and kinetic and thermal stability studies were undertaken. Both enzymes had similar sp. act. in the region of 215 U/mg, with Km values for chloramphenicol in the range 13.8-15.4 microM and for acetyl CoA in the range 13.6-15.5 microM. The A203V mutant shows greater stability than the wild-type Cat-86 protein at temperatures above 50 degrees C and appears to pass through a transition state between 48 and 50 degrees C. PMID- 1438165 TI - Cumulative stabilizing effects of glycine to alanine substitutions in Bacillus subtilis neutral protease. AB - Oligonucleotide-directed mutagenesis has been used to replace glycine residues by alanine in neutral protease from Bacillus subtilis. One Gly to Ala substitution (G147A) was located in a helical region of the protein, while the other (G189A) was in a loop. The effects of mutational substitutions on the functional, conformational and stability properties of the enzyme have been investigated using enzymatic assays and spectroscopic measurements. Single substitutions of both Gly147 and Gly189 with Ala residues affect the enzyme kinetic properties using synthetic peptides as substrates. When Gly replacements were concurrently introduced at both positions, the kinetic characteristics of the double mutant were roughly intermediate between those of the two single mutants, and similar to those of the wild-type protease. Both mutants G147A and G189A were found to be more stable towards irreversible thermal inactivation/unfolding than the wild type species. Moreover, the stabilizing effect of the Gly to Ala substitution was roughly additive in the double mutant G147A/G189A, which shows a 3.2 degrees C increase in Tm with respect to the wild-type protein. These findings indicate that the Gly to Ala substitution can be used as a strategy to stabilize globular proteins. The possible mechanisms of protein stabilization are also discussed. PMID- 1438166 TI - A structural role of histidine 15 in human glutathione transferase M1-1, an amino acid residue conserved in class Mu enzymes. AB - His15 is a conserved amino acid residue in all known class Mu glutathione transferases. This His residue in human glutathione transferase M1-1 has been mutated into 17 different amino acid residues by means of site-directed random mutagenesis to determine if any substitutions are compatible with catalytic activity. The majority of the mutant proteins appeared unstable and could not be isolated in reasonable quantities by heterologous expression in Escherichia coli. Five mutant enzymes, H15C, H15K, H15N, H15Q and H15S were purified and more extensively characterized. The mutant proteins shared the same size as that of the wild-type enzyme but could be separated from the parental enzyme by reverse phase HPLC. For all the mutant forms except H15N, the sp. act. with 1-chloro-2,4 dinitrobenzene was less than 3% of the wild-type value--the H15N mutant enzyme displayed 29% of the wild-type activity. None of the catalytically active mutant enzymes showed any major alteration of the binding affinity for the substrate analog S-hexylglutathione, suggesting that His15 is not part of the active site of the enzyme. The high activity of the mutant H15N, also reflected in the kcat/Km, V and S0.5 values, rules out the possibility that His15 in the native enzyme contributes to catalysis by serving as a base. The role of His15, largely replaceable by Asn in the same position, appears to be structural, probably involving hydrogen bonds that maintain the protein in a stable and catalytically active conformation. A critical structural role of His15 in a buried position may explain the evolutionary conservation of this residue in the class Mu glutathione transferases. PMID- 1438167 TI - Analysis of disulphide bridge function in recombinant bovine prolactin using site specific mutagenesis and renaturation under mild alkaline conditions: a crucial role for the central disulphide bridge in the mitogenic activity of the hormone. AB - We have previously described a method for isolating Escherichia coli-produced methionyl bovine prolactin (Met-bPRL) and its renaturation using thioredoxin. This report describes an alternative renaturation procedure in which extracted Met-bPRL is incubated in air at pH 10 and 20 degrees C. Within 1 h of such treatment essentially all of the reduced Met-bPRL was converted to the oxidized form; this was accompanied by an increase to full mitogenic activity in the Nb2 cell bioassay. It was also found that, to minimize contamination by high mol. wt Met-bPRL derivatives, it is essential to have a reducing agent (dithiothreitol) present during disruption of the bacteria and to extract the protein at neutral pH. The contribution of each of the three disulphide bridges in bPRL to its bioactivity was studied with Met-bPRL variants, prepared via site-specific mutagenesis, in which cysteines were replaced by serines to prevent disulphide bond formation. Variants lacking the C4-C11 bridge, the C191-C199 bridge or both these terminal bridges were as mitogenic as authentic bPRL. (Variants lacking the C191-C199 bridge had markedly increased solubility in the presence of deoxycholate.) In contrast, variants lacking the C58-C174 bridge had greatly reduced bioactivity, indicating that integrity of the large disulphide loop is crucial to the hormone's mitogenic activity. PMID- 1438168 TI - Specificity determinants of rat tissue kallikrein probed by site-directed mutagenesis. AB - Site-specific mutagenesis was employed to study structure-function relationships at the substrate binding site of rat tissue kallikrein. Four kallikrein mutants, the Pro219 deletion (P219del), the 34-38 loop Tyr-Tyr-Phe-Gly to Ile-Asn mutation [YYFG(34-38)IN], the Trp215----Gly exchange (W215G) and the double mutant with Tyr99----His and Trp215----Gly exchange (Y99H:W215G) were created by site directed mutagenesis to probe their function in substrate binding. The mutant proteins were expressed in Escherichia coli at high levels and analyzed by Western blot. These mutant enzymes were purified to apparent homogeneity. Each migrated as a single band on SDS-PAGE, with slightly lower molecular mass (36 kDa) than that of the native enzyme, (38 kDa) because of their lack of glycosylation. The recombinant kallikreins are immunologically identical to the native enzyme, displaying parallelism with the native enzyme in a direct radioimmunoassay for rat tissue kallikrein. Kinetic analyses of Km and kcat using fluorogenic peptide substrates support the hypothesis that the Tyr99-Trp215 interaction is a major determinant for hydrophobic P2 specificity. The results suggest an important role for the 34-38 loop in hydrophobic P3 affinity and further show that Pro219 is essential to substrate binding and efficient catalysis of tissue kallikrein. PMID- 1438169 TI - pH-sensitive interactions between IgG and a mutated IgG-binding protein based upon two B domains of protein A from Staphylococcus aureus. AB - A fusion protein, consisting of the N-terminal 81 amino acids from an inactive bovine DNase I (Q38,E39-E38,Q39) and two sequential synthetic IgG-binding domains based upon domain B of Protein A from Staphylococcus aureus has been shown to bind to porcine IgG with a similar affinity and pH profile to Protein A. The same residue in each B domain (Tyr111 and Tyr169) has been mutated by cassette mutagenesis to Ser, Glu, His, Lys or Arg and the effect of the mutation on binding interactions with porcine IgG investigated. The evidence presented suggests that the interactions at the B domain are highly sensitive to the presence of a charged residue. PMID- 1438170 TI - Overexpression and structure--function analysis of a bioengineered IL-2/IL-6 chimeric lymphokine. AB - A synthetic chimeric IL-2/IL-6 gene was synthesized to engineer a bifunctional lymphokine which was overproduced in Escherichia coli. Following denaturation of the inclusion bodies in 6 M guanidine and refolding and reoxidation in the presence of a redox system, the fusion protein (rIL-2/IL-6) was purified to homogeneity and shown to react with both monospecific anti-IL-2 and anti-IL-6 antisera. A collagen-like spacer was introduced between the two cytokine moieties to generate IL-2 and IL-6 molecules upon collagenase digestion. After cleavage, the two subunits, purified in a single-step procedure, were found to be correctly reoxidized and functionally as active as their native counterparts. Circular dichroism studies of rIL-2/IL-6 revealed that both cytokine subunits refolded independently and exhibited the alpha-helical structures characteristic of the corresponding wild-type lymphokines. The chimera displayed full IL-2 activity in the CTLL-2 cell proliferation assay. It also retained the IL-6 property to enhance IgM synthesis in SKW6.4 cells, induce the proliferation of B-cell hybridomas and stimulate the production of fibrinogen in hepatocytes. Because IL 2 amplifies the cellular immune response and IL-6 up-regulates the humoral response, this bifunctional lymphokine represents a potentially useful therapeutic adduct and may serve as an immunomodulator to enhance the host's response to vaccination. PMID- 1438171 TI - A novel sequential procedure to enhance the renaturation of recombinant protein from Escherichia coli inclusion bodies. PMID- 1438172 TI - The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor. AB - Crystallographic studies of neuraminidase-sialic acid complexes indicate that sialic acid is distorted on binding the enzyme. Three arginine residues on the enzyme interact with the carboxylate group of the sugar which is observed to be equatorial to the saccharide ring as a consequence of its distorted geometry. The glycosidic oxygen is positioned within hydrogen-bonding distance of Asp-151, implicating this residue in catalysis. PMID- 1438173 TI - Mutagenic dissection of hemoglobin cooperativity: effects of amino acid alteration on subunit assembly of oxy and deoxy tetramers. AB - Free energies of oxygen-linked subunit assembly and cooperative interaction have been determined for 34 molecular species of human hemoglobin, which differ by amino acid alterations as a result of mutation or chemical modification at specific sites. These studies required the development of extensions to our earlier methodology. In combination with previous results they comprise a data base of 60 hemoglobin species, characterized under the same conditions. The data base was analyzed in terms of the five following issues. (1) Range and sensitivity to site modifications. Deoxy tetramers showed greater average energetic response to structural modifications than the oxy species, but the ranges are similar for the two ligation forms. (2) Structural localization of cooperative free energy. Difference free energies of dimer-tetramer assembly (oxy minus deoxy) yielded delta Gc for each hemoglobin, i.e., the free energy used for modulation of oxygen affinity over all four binding steps. A structure-energy map constructed from these results shows that the alpha 1 beta 2 interface is a unique structural location of the noncovalent bonding interactions that are energetically coupled to cooperativity. (3) Relationship of cooperativity to intrinsic binding. Oxygen binding energetics for dissociated dimers of mutants strongly indicates that cooperativity and intrinsic binding are completely decoupled by tetramer to dimer dissociation. (4) Additivity, site-site coupling and adventitious perturbations. All these are exhibited by individual-site modifications of this study. Large nonadditivity may be correlated with global (quaternary) structure change. (5) Residue position vs. chemical nature. Functional response is solely dictated by structural location for a subset of the sites, but varies with side-chain type at other sites. The current data base provides a unique framework for further analyses and modeling of fundamental issues in the structural chemistry of proteins and allosteric mechanisms. PMID- 1438174 TI - Regulation of oxygen affinity by quaternary enhancement: does hemoglobin Ypsilanti represent an allosteric intermediate? AB - Recent crystallographic studies on the mutant human hemoglobin Ypsilanti (beta 99 Asp-->Tyr) have revealed a previously unknown quaternary structure called "quaternary Y" and suggested that the new structure may represent an important intermediate in the cooperative oxygenation pathway of normal hemoglobin. Here we measure the oxygenation and subunit assembly properties of hemoglobin Ypsilanti and five additional beta 99 mutants (Asp beta 99-->Val, Gly, Asn, Ala, His) to test for consistency between their energetics and those of the intermediate species of normal hemoglobin. Overall regulation of oxygen affinity in hemoglobin Ypsilanti is found to originate entirely from 2.6 kcal of quaternary enhancement, such that the tetramer oxygenation affinity is 85-fold higher than for binding to the dissociated dimers. Equal partitioning of this regulatory energy among the four tetrameric binding steps (0.65 kcal per oxygen) leads to a noncooperative isotherm with extremely high affinity (pmedian = .14 torr). Temperature and pH studies of dimer-tetramer assembly and sulfhydryl reaction kinetics suggest that oxygenation-dependent structural changes in hemoglobin Ypsilanti are small. These properties are quite different from the recently characterized allosteric intermediate, which has two ligands bound on the same side of the alpha 1 beta 2 interface (see ref. 1 for review). The combined results do, however, support the view that quaternary Y may represent the intermediate cooperativity state of normal hemoglobin that binds the last oxygen. PMID- 1438175 TI - Crystal structure of human immunoglobulin fragment Fab New refined at 2.0 A resolution. AB - The three-dimensional structure of the human immunoglobulin fragment Fab New (IgG1, lambda) has been refined to a crystallographic R-factor of 16.9% to 2 A resolution. Rms deviations of the final model from ideal geometry are 0.014 A for bond distances and 3.03 degrees for bond angles. Refinement was based on a new X ray data set including 28,301 reflections with F > 2.5 sigma(F) from 6.0 to 2.0 A resolution. The starting model for the refinement procedure reported here is from the Brookhaven Protein Data Bank entry 3FAB (rev. 1981). Differences between the initial and final models include modified polypeptide-chain folding in the third complementarity-determining region (CDR3) and the third framework region (FR3) of VH and in some exposed loops of CL and CH1. Amino acid sequence changes were determined at a number of positions by inspection of difference electron density maps. The incorporation of amino acid sequence changes results in an improved VH framework model for the "humanization" of monoclonal antibodies. PMID- 1438176 TI - Limits on alpha-helix prediction with neural network models. AB - Using a backpropagation neural network model we have found a limit for secondary structure prediction from local sequence. By including only sequences from whole alpha-helix and non-alpha-helix structures in our training and test sets- sequences spanning boundaries between these two structures were excluded--it was possible to investigate directly the relationship between sequence and structure for alpha-helix. A group of non-alpha-helix sequences, that was disrupting overall prediction success, was indistinguishable to the network from alpha-helix sequences. These sequences were found to occur at regions adjacent to the termini of alpha-helices with statistical significance, suggesting that potentially longer alpha-helices are disrupted by global constraints. Some of these regions spanned more than 20 residues. On these whole structure sequences, 10 residues in length, a comparatively high prediction success of 78% with a correlation coefficient of 0.52 was achieved. In addition, the structure of the input space, the distribution of beta-sheet in this space, and the effect of segment length were also investigated. PMID- 1438177 TI - Comparative molecular modeling and crystallization of P-30 protein: a novel antitumor protein of Rana pipiens oocytes and early embryos. AB - The P-30 protein (Onconase) of Rana pipiens oocytes and early embryos is homologous to members of the pancreatic ribonuclease superfamily and exhibits an antitumor activity in vitro and in vivo. It appears that the ribonucleolytic activity of P-30 protein may be required for its antitumor effects. A comparative molecular model of P-30 protein has been constructed based upon the known three dimensional structure of bovine pancreatic RNase A in order to provide structural information. Functionally, these enzymes hydrolyze oligoribonucleotides to pyrimidine-3'-phosphate monoesters and 5'-OH ribonucleotides. In the modeling procedure, automated sequence alignments were revised based upon the inspection of the RNase A structure before the amino acids of the P-30 protein were assigned the coordinates of the RNase A template. The inevitable intermolecular steric clashes that result were relieved on an interactive graphics device through the adjustment of side chain torsion angles. This process was followed by energy minimization of the model, which served to optimize stereochemical geometry and to relieve any remaining unacceptably close contacts. The resulting model retains the essential features of RNase A as sequence insertions and deletions are almost exclusively found in exposed surface loops. The all atom superposition of active site residues of the P-30 protein model and an identically minimized RNase A structure has a root mean square deviation of 0.52 A. Though tentative, the model is consistent with a pyrimidine specificity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438178 TI - Structure of a rhombohedral R6 insulin/phenol complex. AB - Hexameric insulin has been crystallized from different conditions in a variety of crystalline modifications. In the presence of approximately 1% phenol and at a pH of 8.5, a new rhombohedral form is produced, space group R3, a = 79.92A and c = 40.39A, in which the asymmetric unit consists of a dimer. The structure has been solved and refined, using data between 8.0 and 2.5A resolution, to a residual of 0.157. The two monomers in the asymmetric unit have nearly identical R conformations, that is, residues B1 through B8 are alpha-helical, producing a continuous alpha-helix from B1 through B19. A phenol molecule is hydrogen bonded to the carbonyl oxygen of A6 Cys of each monomer. Small differences in conformation and the final (2Fo-Fc) and difference electron density maps suggest that an additional phenol molecule is coordinated to one of the two zinc ions. PMID- 1438179 TI - Folding protein alpha-carbon chains into compact forms by Monte Carlo methods. AB - A method is presented for generating folded chains of specific amino acid sequences on a simple cubic lattice. Monte Carlo simulations are used to transform extended geometries of simplified alpha-carbon chains for eight small monomeric globular proteins into folded states. Permitted chain transitions are limited to a few types of moves, all restricted to occur on the lattice. Crude residue-residue potentials derived from statistical structure data are used to describe the energies for each conformer. The low resolution structures obtained by this procedure contain many of the correct gross features of the native folded architectures with respect to average residue energy per nonbonded contact, segment density, and location of surface loops and disulfide pairs. Rms deviations between these and the native X-ray structures and percentage of native long-range contacts found in these final folded structures are 7.6 +/- 0.7 A and 48 +/- 3%, respectively. This procedure can be useful for predicting approximate tertiary interactions from amino acid sequence. PMID- 1438180 TI - What is the pitch of the alpha-helical coiled coil? AB - The alpha-helical, coiled-coil protein motif is increasingly recognized in a variety of functional classes of proteins. The pitch of a coiled coil, or rate of winding of the alpha-helices around each other, is a key determinant of both intra- and intermolecular interactions. Experimental measurements of the pitch of parallel two-stranded coiled coils of muscle proteins, and examination of the recently determined structure of another two-stranded coiled coil, the GCN4 transcription factor protein, suggest that the pitch has an average value of about 140 A. This value is consistent with the observed number of residues per turn in alpha-helices of globular proteins, the determinant of the interhelical packing within the coiled-coil motif. An understanding of the structural determinants of this value for the pitch and possible variations will be important in defining the interactions of coiled-coil proteins with other macromolecules. PMID- 1438181 TI - Generation of a substructure library for the description and classification of protein secondary structure. I. Overview of the methods and results. AB - Protein secondary structure has been typically classified into four major classes -alpha-helices, extended strands, reverse turns, and loops. Available methods for secondary structure analysis utilize predefined structure templates to search for structural matches among proteins. By this approach a significant portion of a proteins backbone conformation is assigned to one of a limited number of conformations or, if unassigned, to random coil. To expand our ability to describe protein secondary structure, we have developed an algorithm that operates independently of a predefined structure template. The procedure uses two geometric descriptors, the linear distance and the backbone dihedral angle, to represent the conformation form the alpha-carbon coordinates. The algorithm functions by searching for conformationally equivalent, contiguous fragments without regard to secondary structural classification and is thus independent of the complexity of the backbone fold. The result is a library of conformationally equivalent structure fragments that exhibit some novel characteristics. The library contains features that reproduce the major secondary structure classes as well as defining conformations previously described only as random or undefined conformations. Additionally, the library defines several subclassifications of beta-strands. We present here a validation of this method and a presentation and discussion of the most significant results. In a second study, we report the results of application of this method to spectra-structure correlations in Fourier transform infrared spectroscopy. PMID- 1438182 TI - Generation of a substructure library for the description and classification of protein secondary structure. II. Application to spectra-structure correlations in Fourier transform infrared spectroscopy. AB - Fourier transform infrared spectroscopy has become well known as a sensitive and informative tool for studying secondary structure in proteins. Present analysis of the conformation-sensitive amide I region in protein infrared spectra, when combined with band narrowing techniques, provides more information concerning protein secondary structure than can be meaningfully interpreted. This is due in part to limited models for secondary structure. Using the algorithm described in the previous paper of this series, we have generated a library of substructures for several trypsin-like serine proteases. This library was used as a basis for spectra-structure correlations with infrared spectra in the amide I' region, for five homologous proteins for which spectra were collected. Use of the substructure library has allowed correlations not previously possible with template-based methods of protein conformational analysis. PMID- 1438183 TI - MD simulation of subtilisin BPN' in a crystal environment. AB - In this paper we present a molecular dynamics (MD) simulation of subtilisin BPN' in a crystalline environment containing four protein molecules and solvent. Conformational and dynamic properties of the molecules are compared with each other and with respect to the X-ray structure to test the validity of the force field. The agreement between simulated and experimental structure using the GROMOS force field is better than that obtained in the literature using other force fields for protein crystals. The overall shape of the molecule is well preserved, as is the conformation of alpha-helices and beta-strands. Structural differences are mainly found in loop regions. Solvent networks found in the X-ray structure were reproduced by the simulation, which was unbiased with respect to the crystalline hydration structure. These networks seem to play an important role in the stability of the protein; evidence of this is found in the structure of the active site. The weak ion binding site in the X-ray structure of subtilisin BPN' is occupied by a monovalent ion. When a calcium ion is placed in the initial structure, three peptide ligands are replaced by 5 water ligands, whereas a potassium ion retains (in part) its original ligands. Existing force fields yield a reliable method to probe local structure and short-time dynamics of proteins, providing an accuracy of about 0.1 nm. PMID- 1438184 TI - Application of a directed conformational search for generating 3-D coordinates for protein structures from alpha-carbon coordinates. AB - A directed conformational search algorithm using the program CONGEN (ref. 3), which samples backbone conformers, is described. The search technique uses information from the partially built structures to direct the search process and is tested on the problem of generating a full set of backbone Cartesian coordinates given only alpha-carbon coordinates. The method has been tested on six proteins of known structure, varying in size and classification, and was able to generate the original backbone coordinates with RMSs ranging from 0.30-0.87A for the alpha-carbons and 0.5-0.99A RMSs for the backbone atoms. Cis peptide linkages were also correctly identified. The procedure was also applied to two proteins available with only alpha-carbon coordinates in the Brookhaven Protein Data Bank; thioredoxin (SRX) and triacylglycerol acylhydrolase (TGL). All-atom models are proposed for the backbone of both these proteins. In addition, the technique was applied to randomized coordinates of flavodoxin to assess the effects of irregularities in the data on the final RMS. This study represents the first time a deterministic conformational search was used on such a large scale. PMID- 1438185 TI - Investigation of the function of mutated cellulose-binding domains of Trichoderma reesei cellobiohydrolase I. AB - The function of the cellulose-binding domain (CBD) of the cellobiohydrolase I of Trichoderma reesei was studied by site-directed mutagenesis of two amino acid residues identified by analyzing the 3D structure of this domain. The mutant enzymes were produced in yeast and tested for binding and activity on crystalline cellulose. Mutagenesis of the tyrosine residue (Y492) located at the tip of the wedge-shaped domain to alanine or aspartate reduced the binding and activity on crystalline cellulose to the level of the core protein lacking the CBD. However, there was no effect on the activity toward small oligosaccharide (4 methylumbelliferyl beta-D-lactoside). The mutation tyrosine to histidine (Y492H) lowered but did not destroy the cellulose binding, suggesting that the interaction of the pyranose ring of the substrate with an aromatic side chain is important. However, the catalytic activity of this mutant on crystalline cellulose was identical to the other two mutants. The mutation P477R on the edge of the other face of the domain reduces both binding and activity of CBHI. These results support the hypothesis that both surfaces of the CBD are involved in the interaction of the binding domain with crystalline cellulose. PMID- 1438186 TI - Modeling the anti-CEA antibody combining site by homology and conformational search. AB - A model for an antibody specific for the carcinoembryonic antigen (CEA) has been constructed using a method which combines the concept of canonical structures with conformational search. A conformational search technique is introduced which couples random generation of backbone loop conformations to a simulated annealing method for assigning side chain conformations. This technique was used both to verify conformations selected from the set of known canonical structures and to explore conformations available to the H3 loop in CEA ab initio. Canonical structures are not available for H3 due to its variability in length, sequence, and observed conformation in known antibody structures. Analysis of the results of conformational search resulted in three equally probable conformations for H3 loop in CEA. Force field energies, solvation free energies, exposure of charged residues and burial of hydrophobic residues, and packing of hydrophobic residues at the base of the loop were used as selection criteria. The existence of three equally plausible structures may reflect the high degree of flexibility expected for an exposed loop of this length. The nature of the combining site and features which could be important to interaction with antigen are discussed. PMID- 1438187 TI - Crystallization, sequence, and preliminary crystallographic data for an antipeptide Fab 50.1 and peptide complexes with the principal neutralizing determinant of HIV-1 gp120. AB - X-ray quality crystals of an Fab fragment from an antipeptide monoclonal antibody (R/V3-50.1) that recognizes the principal neutralizing determinant (PND) of the gp120 glycoprotein of human immunodeficiency virus type 1 (HIV-1) (MN isolate) were grown as uncomplexed and peptide complexed forms. Crystals of the free Fab grew from high salt in orthorhombic space groups P2(1)2(1)2(1) and I222 and from polyethylene glycol in space groups P1 and P2(1). Seeds from either the P1 and P2(1) native (uncomplexed) Fab crystals induced nucleation of crystals of the Fab complexed to a 16-residue synthetic peptide corresponding to the PND when streak seeded into preequilibrated solutions of this complex. Data were collected from these complex crystals and from each of the four native Fab forms to at least 2.8 A resolution. The genes for the variable domain of the Fab were cloned and sequenced and the primary amino acid sequence was deduced from this information. Knowledge of the three-dimensional structure of this Fab-peptide complex will be important in the understanding of the PND of HIV-1 and its recognition by neutralizing monoclonal antibodies. PMID- 1438188 TI - Identification of novel peptide antagonists for GPIIb/IIIa from a conformationally constrained phage peptide library. AB - Methods have recently been developed to present vast libraries of random peptides on the surface of filamentous phage. To introduce a degree of conformational constraint into random peptides, a library of hexapeptides flanked by cysteine residues (capable of forming cyclic disulfides) was constructed. This library was screened using the platelet glycoprotein, IIb/IIIa, which mediates the aggregation of platelets through binding of fibrinogen. A variety of peptides containing the sequence Arg-Gly-Asp or Lys-Gly-Asp were discovered and synthesized. The cyclic, disulfide-bonded forms of the peptides bound IIb/IIIa with dissociation constants in the nanomolar range, while reduced forms or an analogue in which Ser replaced the Cys residues bound considerably less tightly. These results demonstrate the feasibility for introducing conformational constraints into random peptide libraries and also demonstrates the potential for using phage peptide libraries to discover pharmacologically active lead compounds. PMID- 1438189 TI - Binding of sequence-specific proteins to the adenosine- plus uridine-rich sequences of the murine granulocyte/macrophage colony-stimulating factor mRNA. AB - Adenosine+uridine (AU)-rich sequences in the 3' untranslated region (3'UTR) of the mRNA of many cytokines and oncogenes play an important role in mediating RNA degradation. Among the cytokines containing such AU-rich sequences in their 3'UTR is the hematopoietic growth factor granulocyte/macrophage colony-stimulating factor (GM-CSF). GM-CSF gene expression in T cells is regulated by modulation of mRNA half-life. Transfection studies using murine EL-4 thymoma cells have demonstrated that degradation depends on the presence of specific elements in the 3'UTR, including the AU-rich sequences. A number of AU-binding factors have recently been discovered, suggesting that specific regulation may occur through specific protein-mRNA interaction(s). We present evidence from gel-shift analyses and label-transfer experiments that murine cells contain proteins that bind specifically to AU-rich sequences. Three major proteins of 33, 39.5, and 42 kDa are detected. Phorbol ester treatment of cells does not alter the abundance or apparent binding affinity of the proteins. The 33-kDa protein is present in the cytoplasm of murine and human cells, whereas the 39.5- and 42-kDa proteins are present in murine extracts only. Constitutively expressed AU-binding proteins of the type that we describe may function by directing mRNA degradation in the absence of a stimulus to the contrary. PMID- 1438190 TI - Phenotypic and functional immaturity of human umbilical cord blood T lymphocytes. AB - Successful implementation of bone marrow transplantation for hematopoietic reconstitution is limited by the lack of suitably HLA-matched donors and by the occurrence of graft-versus-host disease that frequently accompanies this procedure. Recent clinical reports have implied that the use of umbilical cord blood as a source of transplantable stem cells may solve these problems. To date, definitive experiments have not been performed to assess the immunological potential of T cells found in umbilical cord blood, which could mediate graft versus-host disease. In the present study we have observed that umbilical cord blood contains T lymphocytes that appear to be phenotypically immature. In addition, umbilical cord blood lymphocytes appeared to be functionally immature as shown by minimal responses to stimulation with interleukin 2, phytohemagglutinin, or alloantigens. Thus, umbilical cord blood may be more suitable for allogeneic transplantation than bone marrow in that these cord blood cells may not be as capable of mediating graft-versus-host disease. PMID- 1438191 TI - Complement activation by beta-amyloid in Alzheimer disease. AB - Alzheimer disease (AD) is characterized by excessive deposition of the beta amyloid peptide (beta-AP) in the central nervous system. Although several lines of evidence suggest that beta-AP is neurotoxic, a mechanism for beta-AP toxicity in AD brain remains unclear. In this paper we provide both direct in vitro evidence that beta-AP can bind and activate the classical complement cytolytic pathway in the absence of antibody and indirect in situ evidence that such actions occur in the AD brain in association with areas of AD pathology. PMID- 1438192 TI - A binary plasmid system for shuffling combinatorial antibody libraries. AB - We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind antigen varied from 43% to 100% and depended strongly on the heavy-chain sequence. Such productive crosses resulted in a set of Fab fragments of similar apparent binding constants, which seemed to differ mainly in the amount of active Fab fragment produced in the bacterial cell. The dominance of the heavy chain in the antibody-antigen interaction was further explored in a set of directed crosses, in which heavy and light chains derived from antigen specific clones were crossed with nonrelated heavy and light chains. In these crosses, an Fab fragment retained antigen binding only if it contained a heavy chain from an antigen-specific clone. In no case did the light chain confer detectable affinity when paired with indifferent heavy chains. The surprising promiscuity of heavy chains has ramifications for the evaluation of the diversity of combinatorial libraries made against protein antigens and should allow the combination of one such promiscuous heavy chain with an engineered light chain to form an Fab fragment carrying synthetic cofactors to assist in antibody catalysis. PMID- 1438193 TI - Hepatitis B virus capsid particles are assembled from core-protein dimer precursors. AB - Our studies on the assembly of hepatitis B virus capsids or core particles in Xenopus oocytes have demonstrated that unassembled p21.5 core proteins ("free p21.5") provide a pool of low-molecular-mass precursors for core-particle assembly. Here we have characterized this material. Free p21.5 sedimented through gradients of 3-25% sucrose (wt/vol) as a single protein species of approximately 40 kDa, corresponding to a p21.5 dimer. On nonreducing SDS/polyacrylamide gels, free p21.5 migrated as disulfide-linked p21.5 dimeric species of 35 and 37 kDa. Truncated core proteins lacking most or all of the 36-amino acid protamine region at the p21.5 carboxyl terminus were also found to behave as disulfide-linked dimers with appropriately reduced molecular masses. Our experiments failed to reveal monomeric core proteins or stable intermediates between dimers and capsids along the assembly pathway. We conclude that hepatitis B virus core particles are most likely assembled by aggregating 90 (or possibly 180) disulfide-linked p21.5 dimers. We discuss similarities between the assembly of hepatitis B virus capsids and simple T = 3 plant virus and bacteriophage structures. PMID- 1438194 TI - Retinoic acid is enriched in Hensen's node and is developmentally regulated in the early chicken embryo. AB - Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring tissues. Furthermore, stage 6 Hensen's node contains approximately 3 times more retinoid than that of stage 4 embryos. These endogenous retinoids may establish a concentration gradient from Hensen's node to adjacent tissues and play a role in establishing the primary embryonic axis in the vertebrate. The results also suggest that the retinoid concentration in Hensen's node is developmentally regulated. PMID- 1438195 TI - Large, identical, tandem repeating units in the C protein alpha antigen gene, bca, of group B streptococci. AB - Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis in the United States. The surface-associated C protein alpha antigen of GBS is thought to have a role in both virulence and immunity. We previously cloned the C protein alpha antigen structural gene (named bca for group B, C protein, alpha) into Escherichia coli. Western blots of both the native alpha antigen and the cloned gene product demonstrate a regularly laddered pattern of heterogeneous polypeptides. The nucleotide sequence of the bca locus reveals an open reading frame of 3060 nucleotides encoding a precursor protein of 108,705 Da. Cleavage of a putative signal sequence of 41 amino acids yields a mature protein of 104,106 Da. The 20,417-Da N-terminal region of the alpha antigen shows no homology to previously described protein sequences and is followed by a series of nine tandem repeating units that make up 74% of the mature protein. Each repeating unit is identical and consists of 82 amino acids with a molecular mass of 8665 Da, which is encoded by 246 nucleotides. The size of the repeating units corresponds to the observed size differences in the heterogeneous ladder of alpha C proteins expressed by GBS. The C-terminal region of the alpha antigen contains a membrane anchor domain motif that is shared by a number of Gram-positive surface proteins. The large region of identical repeating units in bca defines protective epitopes and may play a role in generating phenotypic and genotypic diversity of the alpha antigen. PMID- 1438196 TI - Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes. AB - Survival of Salmonella typhimurium within macrophage phagosomes requires the coordinate expression of bacterial gene products. This report examines the contribution of phagosomal pH as a signal for expression of genes positively regulated by the S. typhimurium virulence regulators PhoP and PhoQ. Several hours after bacterial phagocytosis by murine bone marrow-derived macrophages, PhoP activated gene transcription increased 50- to 77-fold. In contrast, no difference in PhoP-activated gene expression was observed after infection of cultured epithelial cells, suggesting that the membrane sensor PhoQ recognized signals unique to macrophage phagosomes. The increase in PhoP-regulated gene expression was abolished when macrophage culture medium contained NH4Cl or chloroquine, weak bases that raise the pH of acidic compartments. Measurements of pH documented that S. typhimurium delayed and attenuated acidification of its intracellular compartment. Phagosomes containing S. typhimurium required 4-5 hr to reach pH < 5.0. In contrast, within 1 hr vacuoles containing heat-killed bacteria were measured at pH < 4.5. The eventual acidification of phagosomes to pH < 5.0 correlated with the period of maximal PhoP-dependent gene expression. These observations implicate phagosome acidification as an intracellular inducer of PhoP-regulated gene expression and suggest that Salmonella survival is dependent on its ability to attenuate phagosome acidification. PMID- 1438197 TI - Retention of habituation in PC12 cells. AB - The time course of habituation and recovery of neurotransmitter release was measured in neuronally differentiated PC12 cells stimulated with either acetylcholine or ATP. The release of norepinephrine in response to either stimulant declined exponentially with repeated presentation of that stimulant. When the stimulus was withheld, the cells' ability to respond recovered to initial levels with an exponential time course. The rate of response recovery depended on the stimulant used and, in the case of stimulation with acetylcholine, on the number of previous stimuli. After habituation and recovery, or partial recovery, of norepinephrine release, the response to a second series of repetitive stimuli declined more rapidly than in the naive case. This increase in habituation rate was dependent on the number of previous stimuli and, in the case of stimulation with acetylcholine, was stable with time for at least 90 min after stimulation. These phenomena are analogous to characteristics of short- and long-term memories of habituative learning observed in behavioral studies. Kinetic equations based on a putative reversible stimulation-dependent inactivation of the cellular response mechanism were used to analyze the rates of habituation and response recovery. PMID- 1438198 TI - Structural analysis of ternary complexes of vaccinia RNA polymerase. AB - The structure of the elongation complex of vaccinia RNA polymerase halted at discrete template positions was examined by DNase I footprinting. The leading edge of the footprint bore a constant relationship to the catalytic template position, being 22-24 nucleotides (nt) in advance on the nontemplate strand and 17 nt on the template strand. DNase hypersensitivity of the nontemplate strand at the leading edge suggested that the DNA might be distorted as it entered the polymerase molecule. The region of DNA unwinding at the transcription bubble extended at least 12 nt 5' from the catalytic center, as indicated by the reactivity of adenosine residues to diethylpyrocarbonate. Cu-phenanthroline hypersensitive sites located 13 nt 5' and 4 nt 3' of the growing point appeared to demarcate the margins of the bubble. Strand asymmetry of chemical modification within the bubble was consistent with an RNA-DNA hybrid of no more than 10 base pairs. PMID- 1438199 TI - Telomere length predicts replicative capacity of human fibroblasts. AB - When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite replicative capacity is explained by the chronological age of the donor. Because we had previously shown that telomeres, the terminal guanine-rich sequences of chromosomes, shorten throughout the life-span of cultured cells, we wished to determine whether variation in initial telomere length would account for the unexplained variation in replicative capacity. Analysis of cells from 31 donors (aged 0-93 yr) indicated relatively weak correlations between proliferative ability and donor age (m = 0.2 doubling per yr; r = -0.42; P = 0.02) and between telomeric DNA and donor age (m = -15 base pairs per yr; r = -0.43; P = 0.02). However, there was a striking correlation, valid over the entire age range of the donors, between replicative capacity and initial telomere length (m = 10 doublings per kilobase pair; r = 0.76; P = 0.004), indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. These observations suggest that telomere length is a biomarker of somatic cell aging in humans and are consistent with a causal role for telomere loss in this process. We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. In contrast, telomeres from sperm DNA did not decrease with age of the donor, suggesting that a mechanism for maintaining telomere length, such as telomerase expression, may be active in germ-line tissue. PMID- 1438200 TI - Comparison of the NMR solution structure and the x-ray crystal structure of rat metallothionein-2. AB - Metallothioneins are small cysteine-rich proteins capable of binding heavy metal ions such as Zn2+ and Cd2+. They are ubiquitous tissue components in higher organisms, which tentatively have been attributed both unspecific protective functions against toxic metal ions and highly specific roles in fundamental zinc regulated cellular processes. In this paper a detailed comparison of the NMR solution structure [Schultze, P., Worgotter, E., Braun, W., Wagner, G., Vasak, M., Kagi, J. H. R. & Wuthrich, K. (1988) J. Mol. Biol. 203, 251-268] and a recent x-ray crystal structure [Robbins, A. H., McRee, D. E., Williamson, M., Collett, S. A., Xoung, N. H., Furey, W. F., Wang, B. C. & Stout, C. D. (1991) J. Mol. Biol. 221, 1269-1293] of rat metallothionein-2 shows that the metallothionein structures in crystals and in solution have identical molecular architectures. The structures obtained with both techniques now present a reliable basis for discussions on structure-function correlations in this class of metalloproteins. PMID- 1438201 TI - Immobilization of DNA for scanning probe microscopy. AB - Reproducible scanning tunneling microscope and atomic force microscope images of entire molecules of uncoated plasmid DNA chemically bound to surfaces are presented. The chemically mediated immobilization of DNA to surfaces and subsequent scanning tunneling microscope imaging of DNA molecules demonstrate that the problem of molecular instability to forces exerted by the probe tip, inherent with scanning probe microscopes, can be prevented. PMID- 1438202 TI - The same exhaustible multilineage precursor produces both myeloid and lymphoid cells as early as 3-4 weeks after marrow transplantation. AB - Hemopoietic precursors with the ability to differentiate into wide varieties of cell types are considered primitive, as are precursors with long-term repopulating ability. Here we study the populations of marrow precursors from which both myeloid and lymphoid lineages are descended shortly after transplantation. Surprisingly, few or none of these precursors show long-term repopulating ability. Equal portions of a mixture of marrow cells from C57BL/6J (B6) and congenic B6-Hbbd Gpi-1a mice are transplanted into a group of recipients. Three weeks later, highly significant correlations between percentages of B6 type T cells, B cells, granulocytes, and platelets in each recipient indicate that many lymphoid and myeloid cells are descended from common precursors. After 4-6 weeks, most correlations between lymphoid and myeloid cells improve, indicating that most or all differentiated cells are descended from common precursors. The more differentiated myeloid-specific precursors found in spleen colony-forming cell assays apparently fail to contribute significantly to the differentiated myeloid cell populations tested. By using the binomial model, in which variability of the data among the recipients is inversely related to the number of precursors in the mixture, donor precursor concentrations are estimated as approximately 21 per 10(5) marrow cells after 3 weeks, falling 3-fold to 6.6 per 10(5) after 4-6 weeks. This trend continues, with higher correlations, greater variabilities, and donor precursor concentrations of 1.9 per 10(5) marrow cells after 12-14 weeks and 1.4 per 10(5) after 24 weeks. Strong increases in variances between 3 and 12 weeks after transplantation suggest that most or all of the initially active multilineage precursors are exhausted during this time period. The fact that the ability of a hemopoietic stem cell to differentiate into widely disparate lineages is not associated with long-term repopulating ability requires a change in stem cell definitions, since primitive hemopoietic stem cells have traditionally been defined by both these abilities. PMID- 1438203 TI - Structure of the ColE1 DNA molecule before segregation to daughter molecules. AB - The segregation of daughter DNA molecules at the end stage of replication of plasmid ColE1 was examined. When circular ColE1 DNA replicates in a cell extract at a high KCl concentration (140 mM), a unique class of molecules accumulates. When the molecule is cleaved by a restriction enzyme that cuts the ColE1 DNA at a single site, an X-shaped molecule in which two linear components are held together around the origin of DNA replication is made. For a large fraction of these molecules, the 5' end of the leading strand remains at the origin and the 3' end of the strand is about 30 nucleotides upstream of the origin. The 3' end of the lagging strand is located at the terH site (17 nucleotides upstream of the origin) and the 5' end of the strand is a few hundred nucleotides upstream of the terH site. Thus the parental strands of the molecule intertwine with each other only once. When the KCl concentration is lowered to 70 mM, practically all of these molecules are converted to daughter circular monomers or to catenanes consisting of two singly interlocked circular units. PMID- 1438204 TI - Time-resolved circularly polarized protein phosphorescence. AB - The existence of circular polarization in room-temperature protein phosphorescence is demonstrated, and time-resolved circularly polarized phosphorescence (TR-CPP) is used to characterize unique tryptophan environments in multitryptophan proteins. Circularly polarized luminescence studies provide information regarding the excited state chirality of a lumiphore which can be used to extract sensitive structural information. It is shown by time resolving the circular polarization that it is possible to correlate the excited state chirality with unique decay components in a multiexponential phosphorescence decay profile. The present study presents a concurrent analysis of room temperature time-resolved phosphorescence and TR-CPP of bacterial glucose-6 phosphate dehydrogenase as well as those of horse liver alcohol dehydrogenase. Only one of the two tryptophan residues per subunit of dimeric alcohol dehydrogenase is believed to phosphorescence, while the dimeric glucose-6 phosphate dehydrogenase has eight tryptophan residues per subunit and shows a corresponding complexity in its phosphorescence decay profile. The anisotropy factor [g(em) = delta I/(Itotal/2); delta I = Ileft circular-Iright circular] for alcohol dehydrogenase is time independent, suggesting a unique excited state chirality. The phosphorescence decay of glucose-6-phosphate dehydrogenase can be well fitted with four exponential terms of 4, 23, 76, and 142 msec, and the TR CPP of this enzyme shows a strong time dependence that can be resolved into four individual time-independent anisotropy factors of -4.0, -2.1, +6.5, and +6.9 (x10(-3)), each respectively associated with one of the four lifetime components. These results demonstrate how the use of TR-CPP can facilitate the study of proteins with multiple lumiphores. PMID- 1438205 TI - Cell division arrest induced by phorbol ester in CHO cells overexpressing protein kinase C-delta subspecies. AB - Several lines of CHO cells stably overexpressing protein kinase C (PKC) subspecies to various extents were established by the DNA-mediated transfer. Upon treatment with phorbol 12-myristate 13-acetate, the growth of the cells expressing the PKC-delta subspecies was markedly inhibited, whereas cell lines expressing PKC-alpha, PKC-beta II, and PKC-zeta subspecies were not significantly affected. Flow cytometric analysis indicated that all cell lines overexpressing PKC-delta subspecies accumulated in G2/M phase in response to phorbol 12 myristate 13-acetate. In these arrested cells, dikaryons were predominant, implying that phorbol ester-induced inhibition of cell division is specific to telophase. These results suggest PKC-delta subspecies may play a role in the normal cell cycle progression. PMID- 1438206 TI - Ser-752-->Pro mutation in the cytoplasmic domain of integrin beta 3 subunit and defective activation of platelet integrin alpha IIb beta 3 (glycoprotein IIb IIIa) in a variant of Glanzmann thrombasthenia. AB - Integrins are membrane receptors which mediate cell-cell or cell-matrix adhesion. Integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) acts as a fibrinogen receptor of platelets and mediates platelet aggregation. Platelet activation is required for alpha IIb beta 3 to shift from noncompetent to competent for binding soluble fibrinogen. The steps involved in this transition are poorly understood. We have studied a variant of Glanzmann thrombasthenia, a congenital bleeding disorder characterized by absence of platelet aggregation and fibrinogen binding. The patient's platelets did not bind fibrinogen after platelet activation by ADP or thrombin, though his platelets contained alpha IIb beta 3. However, isolated alpha IIb beta 3 was able to bind to an Arg-Gly-Asp-Ser affinity column, and binding of soluble fibrinogen to the patient's platelets could be triggered by modulators of alpha IIb beta 3 conformation such as the Arg-Gly-Asp-Ser peptide and alpha-chymotrypsin. These data suggested that a functional Arg-Gly-Asp binding site was present within alpha IIb beta 3 and that the patient's defect was not secondary to a blockade of alpha IIb beta 3 in a noncompetent conformational state. This was evocative of a defect in the coupling between platelet activation and alpha IIb beta 3 up-regulation. We therefore sequenced the cytoplasmic domain of beta 3, following polymerase chain reaction (PCR) on platelet RNA, and found a T-->C mutation at nucleotide 2259, corresponding to a Ser-752-->Pro substitution. This mutation is likely to be responsible for the uncoupling of alpha IIb beta 3 from cellular activation because (i) it is not a polymorphism, (ii) it is the only mutation in the entire alpha IIb beta 3 sequence, and (iii) genetic analysis of the family showed that absence of the Pro 752 beta 3 allele was associated with the normal phenotype. Our data thus identify the C-terminal portion of the cytoplasmic domain of beta 3 as an intrinsic element in the coupling between alpha IIb beta 3 and platelet activation. PMID- 1438207 TI - Isolation of a wheat cDNA clone for an abscisic acid-inducible transcript with homology to protein kinases. AB - Increases in the plant hormone abscisic acid (ABA) initiate water-stress responses in plants. We present evidence that a transcript with homology to protein kinases is induced by ABA and dehydration in wheat. A 1.2-kilobase cDNA clone (PKABA1) was isolated from an ABA-treated wheat embryo cDNA library by screening the library with a probe developed by polymerase chain reaction amplification of serine/threonine protein kinase subdomains VIb to VIII. The deduced amino acid sequence of the PKABA1 clone contains the features of serine/threonine protein kinases, including homology with all 12 conserved regions of the catalytic domain. PKABA1 transcript levels are barely detectable in growing seedlings but are induced dramatically when plants are subjected to dehydration stress. The PKABA1 transcript can also be induced by supplying low concentrations of ABA, and coordinate increases in ABA levels and PKABA1 mRNA occur when seedlings are water-stressed. Identification of this ABA-inducible transcript with homology to protein kinases provides a basis for examining the role of protein phosphorylation in plant responses to dehydration. PMID- 1438208 TI - Cloning and expression of an NADP(+)-dependent alcohol dehydrogenase gene of Entamoeba histolytica. AB - Ethanol is the major metabolic product of glucose fermentation by the protozoan parasite Entamoeba histolytica under the anaerobic conditions found in the lumen of the colon. Here an internal peptide sequence determined from a major 39-kDa amoeba protein isolated by isoelectric focusing followed by SDS/PAGE was used to clone the gene for the E. histolytica NADP(+)-dependent alcohol dehydrogenase (EhADH1; EC 1.1.1.2). The EhADH1 clone had an open reading frame that was 360 amino acids long and encoded a protein of approximately 39 kDa (calculated size). EhADH1 showed a 62% amino acid identity with the tetrameric NADP(+)-dependent alcohol dehydrogenase of Thermoanaerobium brockii. In contrast, EhADH1 showed a 15% amino acid identity with the closest human alcohol dehydrogenase. EhADH1 contained 18 of the 22 amino acids conserved in other alcohol dehydrogenases, including glycines involved in binding NAD(P)+ as well as histidine and cysteine residues involved in binding the catalytic zinc ion. Like the T. brockii alcohol dehydrogenase, EhADH1 lacked a 23-amino acid stretch present in other alcohol dehydrogenases that includes four cysteines that bind a second noncatalytic zinc ion. An EhADH1-glutathione-S-transferase fusion protein showed the expected NADP(+)-dependent alcohol dehydrogenase and NADPH-dependent acetaldehyde reductase activities. The enzymatic activities of the EhADH1 fusion protein were inhibited by pyrazole and 4-methylpyrazole. PMID- 1438209 TI - Homocysteine and other sulfhydryl compounds enhance the binding of lipoprotein(a) to fibrin: a potential biochemical link between thrombosis, atherogenesis, and sulfhydryl compound metabolism. AB - We have previously shown that lipoprotein(a) [Lp(a)], an atherogenic lipoprotein that contains apolipoprotein(a), which shares partial structural homology to plasminogen, binds to a plasmin-modified fibrin surface, and we have postulated that this interaction may be atherogenic. Moderate elevations in blood homocysteine, a relatively common condition, predispose to premature atherosclerosis. The reasons for this are not established. We now report that homocysteine, at concentrations as low as 8 microM, significantly increases the affinity of Lp(a) for fibrin. Homocysteine induces a 20-fold increase in the affinity between Lp(a) and plasmin-treated fibrin and a 4-fold increase with unmodified fibrin. Lp(a) binding is inhibited by epsilon-aminocaproic acid, indicating lysine binding site specificity. Homocysteine does not enhance the binding of Lp(a) to other surface-bound proteins. Cysteine, glutathione, and N acetylcysteine also increase the affinity between Lp(a) and fibrin. Homocysteine does not affect the binding of low density lipoprotein or plasminogen to fibrin, nor does it alter the gel-filtration elution pattern of Lp(a). Immunoblot analysis documents the fact that homocysteine partially reduces Lp(a). These results suggest that homocysteine alters the intact Lp(a) particle so as to increase the reactivity of the plasminogen-like apolipoprotein(a) portion of the molecule. The observation that sulfhydryl amino acids increase Lp(a) binding to fibrin suggests a biochemical relationship between sulfhydryl compound metabolism, thrombosis, and atherogenesis. PMID- 1438210 TI - Tagging of plant potyvirus replication and movement by insertion of beta glucuronidase into the viral polyprotein. AB - Infectious RNA transcripts were generated from full-length cDNA clones of the tobacco etch potyvirus genome containing an insertion of the bacterial beta glucuronidase (GUS) gene between the polyprotein-coding sequences for the N terminal 35-kDa proteinase and the helper component-proteinase. The recombinant virus was able to spread systemically in plants and accumulated to a level comparable with wild-type tobacco etch potyvirus. Proteolytic processing mediated by the 35-kDa proteinase and helper component-proteinase resulted in production of an enzymatically active GUS-helper component-proteinase fusion protein. A virus passage line that retained the GUS insert after numerous plant-to-plant transfers, as well as a line that sustained a deletion of the GUS sequence, was recovered. Use of an in situ histochemical GUS assay in time-course experiments allowed the visualization of virus activity in single, mechanically inoculated leaf epidermal cells, in neighboring epidermal and mesophyll cells, in phloem associated cells after long-distance transport, and in cells surrounding vascular tissues of organs above and below the site of inoculation. This system represents a powerful tool to study plant virus replication, short- and long-distance virus movement, and virus-host interactions. Additionally, we show that potyviruses may serve as highly efficient, autonomously replicating vectors for the expression of foreign genes in plants. PMID- 1438211 TI - CD22-mediated stimulation of T cells regulates T-cell receptor/CD3-induced signaling. AB - Interaction between B lymphocytes and other cell types is mediated in part by the B-cell adhesion molecule CD22. Recent work has suggested one of the T-cell ligands of B cells to be CD45RO, an isoform of the receptor-linked phosphotyrosine phosphatase CD45. Here we demonstrate direct interaction between CD22 and several isoforms of CD45, including CD45RO, and propose that the interaction may participate in regulation of lymphocyte signaling. Cross-linking of CD3 and CD22 T-cell ligands with anti-CD3 antibody and soluble CD22 is shown to block anti-CD3-induced intracellular calcium increase and to inhibit tyrosine phosphorylation of phospholipase C gamma 1. These effects are consistent with those observed upon coligation of CD3 and CD45 with antibody, providing support to the possibility that ligand-mediated stimulation of CD45 may result in modulation of substrate phosphorylation and lymphocyte activation. PMID- 1438212 TI - Relationship of human immunodeficiency virus type 1 sequence heterogeneity to stage of disease. AB - V3 envelope sequences were determined from amplified human immunodeficiency virus type 1 (HIV-1) sequences of uncultivated leukocytes obtained sequentially from four infected adults over the course of infection. Lower levels of sequence heterogeneity were noted in samples obtained early in HIV-1 infection, prior to CD4 depletion, than in samples obtained at later times during disease. The pattern of amino acid sequence divergence included nonrandom changes, with evidence of sequence variants arising from HIV-1 quasi-species present earlier in infection. Consensus sequences for isolates obtained early after infection from different patients demonstrated a high level of conservation with one another and a consensus sequence for macrophage-tropic HIV-1 isolates. These findings suggest that a highly restricted subset of HIV-1 quasi-species can be transmitted and can establish infection. PMID- 1438213 TI - A periplasmic protein disulfide oxidoreductase is required for transformation of Haemophilus influenzae Rd. AB - The mutated gene in JG16, a Haemophilus influenzae strain deficient in competence induced DNA binding and uptake, was cloned and the wild-type allele was sequenced. The gene was shown by Northern analysis to be constitutively expressed on a 1.7-kilobase transcript. The gene product was identified as a 20.6-kDa protein targeted to the periplasm. The protein contains the sequence Cys-Pro-His Cys (CPHC) and is highly similar to two other periplasmic CPHC motif-containing proteins: DsbA, an Escherichia coli protein (45% identity, 87% homology) and TcpG, a Vibrio cholerae protein (32% identity, 74% homology). Both DsbA and TcpG promote disulfide bond formation in periplasmic proteins, are required for pilus biogenesis, and, like thioredoxin, are capable of reducing insulin in vitro. The Haemophilus protein was shown to complement an E. coli mutation in DsbA and was named Por (periplasmic oxidoreductase). In JG16 the competence-dependent redistribution of inner membrane proteins did not occur. These findings suggest that Por is required for the correct assembly and/or folding of one or more disulfide-containing cell envelope protein involved either in competence development or in the DNA-binding and -uptake machinery. PMID- 1438214 TI - Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin. AB - Proteolytic cleavage of the protective antigen (PA) protein of anthrax toxin at residues 164-167 is necessary for toxic activity. Cleavage by a cellular protease at this sequence, Arg-Lys-Lys-Arg, normally follows binding of PA to a cell surface receptor. We attempted to identify this protease by determining its sequence specificity and catalytic properties. Semi-random cassette mutagenesis was used to generate mutants with replacements of residues 164-167 by Arg, Lys, Ser, or Asn. Analysis of 19 mutant proteins suggested that lethal factor dependent toxicity required the sequence Arg-Xaa-Xaa-Arg. Based on these data, three additional mutants were constructed with the sequences Ala-Lys-Lys-Arg, Arg Lys-Lys-Ala, and Arg-Ala-Ala-Arg. Of these mutant proteins, Arg-Ala-Ala-Arg was toxic, confirming that the cellular protease can recognize the sequence Arg-Xaa Xaa-Arg. The mutant containing the sequence Ala-Lys-Lys-Arg was also toxic but required > 13 times more protein to produce equivalent toxicity. This sequence specificity is similar to that of the ubiquitous subtilisin-like protease furin, which is involved in processing of precursors of certain receptors and growth factors. Therefore we tested whether a recombinant soluble furin would cleave PA. This furin derivative efficiently cleaved native PA and the Arg-Ala-Ala-Arg mutant but not the nontoxic PA mutants. In addition, previously identified inhibitors of furin blocked cleavage of receptor-bound PA. These data imply that furin is the cellular protease that activates PA, and that nearly all cell types contain at least a small amount of furin exposed on their cell surface. PMID- 1438215 TI - A histidine protein kinase homologue required for regulation of bacterial cell division and differentiation. AB - Differentiation in the dimorphic bacterium Caulobacter crescentus results from a sequence of discontinuous, stage-specific events that leads to the production of a stalked cell and a new motile swarmer cell after each asymmetric cell division. As reported previously, pseudoreversion analysis of mutations in the pleiotropic developmental gene pleC identified three cell division genes: divJ, divK, and divL. We show here that one of these genes, divJ, encodes a predicted protein of 596 residues with an extensive hydrophobic N-terminal region and a C-terminal domain containing all of the invariant residues found in the family of bacterial histidine protein kinases. Our results also show that divJ is discontinuously transcribed early in the swarmer cell cycle during a period that coincides with the G1 to S transition. We propose that the DivJ protein is one member of a signal transduction pathway regulating the cell cycle and differentiation in Caulobacter and that protein modification by phosphorylation may play a central role in coupling developmental events to progress through the cell division cycle. PMID- 1438216 TI - Somatic recombination of heavy chain variable region transgenes with the endogenous immunoglobulin heavy chain locus in mice. AB - Transgenic lines of mice were derived by using plasmid constructs containing DNA encoding an antibody heavy chain variable-diversity-joining region (VH-D-JH) and various amounts of 5' and 3' flanking DNA but lacking any repetitive isotype switch (S) or constant (C) region DNA. Unexpectedly, many of the antibody VH regions expressed by B-cell hybridomas generated from immunized transgenic mice were found to be of transgenic origin. Further analyses showed that somatic events had generated hybrid genomic loci in the mice containing the transgenic VH D-JH gene and plasmid sequences 5' of endogenous heavy chain C region genes. Thus, VH-D-JH transgenes lacking S and C region DNA can recombine with endogenous Igh DNA, leading to the expression of transgene-encoded antibody. PMID- 1438217 TI - Induction of the neural cell adhesion molecule and neuronal aggregation by osteogenic protein 1. AB - The neural cell adhesion molecule (N-CAM) plays a fundamental role in nervous system development and regeneration, yet the regulation of the expression of N CAM in different brain regions has remained poorly understood. Osteogenic protein 1 (OP-1) is a member of the transforming growth factor beta superfamily that is expressed in the nervous system. Treatment of the neuroblastoma-glioma hybrid cell line NG108-15 for 1-4 days with recombinant human OP-1 (hOP-1) induced alterations in cell shape, formation of epithelioid sheets, and aggregation of cells into multilayered clusters. Immunofluorescence studies and Western blots demonstrated a striking differential induction of the three N-CAM isoforms in hOP 1-treated cells. hOP-1 caused a 6-fold up-regulation of the 140-kDa N-CAM, the isoform showing the highest constitutive expression, and a 29-fold up-regulation of the 180-kDa isoform. The 120-kDa isoform was not detected in control NG108-15 cells but was readily identified in hOP-1-treated cells. Incubation of NG108-15 cells with an antisense N-CAM oligonucleotide reduced the induction of N-CAM by hOP-1 and decreased the formation of multilayered cell aggregates. Anti-N-CAM monoclonal antibodies also diminished the formation of multilayered cell aggregates by hOP-1 and decreased cell-cell adhesion when hOP-1-treated NG108-15 cells were dispersed and replated. Thus, hOP-1 produces morphologic changes in NG108-15 cells, at least in part, by inducing N-CAM. These observations suggest that OP-1 or a homologue may participate in the regulation of N-CAM during nervous system development and regeneration. PMID- 1438219 TI - Quadruplex structure of d(G3T4G3) stabilized by K+ or Na+ is an asymmetric hairpin dimer. AB - The ends of chromosomes contain repeats of guanine-rich sequences that can assume highly compact conformations and are presumed necessary for their biological role in chromosomal stabilization and association. We have investigated the conformational behavior of d(G3T4G3) as a function of the addition of either KCl or NaCl, in the concentration range of 50-200 mM, by using a spectrum of physical techniques and conclude that these salts induce a quadruplex species composed of two strands, each in a hairpin conformation. When salt is added, a large positive signal appears near 290 nm in the CD spectra. UV thermal denaturation curves show a single concentration-dependent transition and provide data for quantitating the thermodynamics of quadruplex formation. In electrophoresis experiments, the quadruplex structure migrates as a single species and more rapidly than the unstructured single strand. NMR spectra in the presence of KCl or NaCl indicate that the structure formed is asymmetric. Equilibrium ultracentrifugation studies confirm that these quadruplexes are composed of two strands of d(G3T4G3). Possible models for this structure are discussed. PMID- 1438218 TI - Alternative splicing generates metabotropic glutamate receptors inducing different patterns of calcium release in Xenopus oocytes. AB - A splice variant of the metabotropic glutamate receptor (mGluR) 1a, named mGluR1c, was isolated. Compared to mGluR1a, the predicted mGluR1c protein is 302 amino acids shorter at its C-terminal end. Despite this difference, mGluR1c activates phospholipase C in Xenopus oocytes with a pharmacological profile identical to that of mGluR1a. However, in contrast to the large fast transient responses induced by mGluR1a, mGluR1c receptors elicit a small more slowly generated long-lasting oscillatory current, suggesting that these two receptors do not generate the same pattern of Ca2+ release in Xenopus oocytes. In situ hybridization data show that mGluR1c mRNA is expressed at a lower level than the other splice variants of mGluR1. Some differences in the regional distribution of these transcripts were observed in the cerebellum, the olfactory bulb, and the striatum. PMID- 1438220 TI - DnaJ, DnaK, and GrpE heat shock proteins are required in oriP1 DNA replication solely at the RepA monomerization step. AB - We have found that three Escherichia coli heat shock proteins, DnaK (the hsp70 homolog), DnaJ, and GrpE, function in oriP1 DNA replication in vitro solely to activate DNA binding by the replication initiator protein RepA. Activation results from the conversion of P1 or P7 RepA dimers to monomers that bind with high affinity to the origin of replication of plasmid P1. Thus, the essential role of these three heat shock proteins in this replication system is to change the quaternary structure of a single protein, RepA. PMID- 1438221 TI - Adaptive cellular interactions in the immune system: the tunable activation threshold and the significance of subthreshold responses. AB - A major challenge for immunologists is to explain how the immune system adjusts its responses to the microenvironmental context in which antigens are recognized. We propose that lymphocytes achieve this by tuning and updating their responsiveness to recurrent signals. In particular, cellular anergy in vivo is a dynamic state in which the threshold for a stereotypic mode of activation has been elevated. Anergy is associated with other forms of cellular activity, not paralysis. Cells engaged in such subthreshold interactions mediate functions such as maintenance of immunological memory and control of infections. In such interactions, patterns of signals are recognized and classified and evoke selective responses. The robust mechanism proposed for segregation of suprathreshold and subthreshold immune responses allows lymphocytes to use recognition of self-antigens in executing physiological functions. Autoreactivity is allowed where it is dissociated from uncontrolled aggression. PMID- 1438222 TI - Uptake of exogenous free cholesterol induces upregulation of tissue factor expression in human monocyte-derived macrophages. AB - Lipid-laden macrophages present as foam cells may contribute to the hyperthrombotic state of human atherosclerotic lesions by the production of tissue factor (TF). We investigated the effect of exogenous nonlipoprotein cholesterol on the expression of TF by human monocyte-derived macrophages in culture. Nonlipoprotein cholesterol at 50 micrograms/ml increased TF activity 4 fold; TF induction was dose- and time-dependent. Expression of TF activity was positively correlated with the free cholesterol content of monocyte-derived macrophages, was increased upon inhibition of cholesterol esterification, and reflected de novo synthesis of TF protein. TF expression in cholesterol-loaded macrophages remained sensitive to stimulation (approximately 12-fold) by bacterial lipopolysaccharide, indicating that intracellular free cholesterol and lipopolysaccharide act by distinct mechanisms in inducing TF procoagulant activity. Our results suggest that loading human monocyte-derived macrophages with free cholesterol induces upregulation of TF expression, thereby contributing to thrombus formation at sites of plaque rupture. PMID- 1438223 TI - Macrophages in Drosophila embryos and L2 cells exhibit scavenger receptor mediated endocytosis. AB - Mammalian macrophage scavenger receptors exhibit unusually broad binding specificity and are implicated in atherosclerosis and host defense. Scavenger receptor-like endocytosis was observed in Drosophila melanogaster embryos and in primary embryonic cell cultures. This receptor activity was expressed primarily by macrophages. The Drosophila Schneider L2, but not the Kc, cell line also exhibited a scavenger receptor-mediated endocytic pathway similar to its mammalian counterpart. L2 receptors mediated high-affinity internalization and subsequent temperature- and chloroquine-sensitive degradation of 125I-labeled acetylated low density lipoprotein and displayed characteristic ligand specificity. These findings suggest that scavenger receptors mediate important, well-conserved functions and raise the possibility that they may be pattern recognition receptors that arose early in the evolution of host defense mechanisms. They also establish additional systems for the investigation of endocytosis in Drosophila and scavenger receptor function in disease, host defense, and development. PMID- 1438224 TI - Identification of the gene for an Escherichia coli poly(A) polymerase. AB - Many bacterial mRNAs, like those of eukaryotes, carry a polyadenylate sequence at their 3' termini, but neither the function of the bacterial poly(A) moieties nor their biosynthesis have been elucidated. To develop a genetic tool to approach the problem of bacterial poly(A) RNA, we have sought to identify the genes responsible for mRNA polyadenylylation. A poly(A) polymerase was purified to homogeneity from extracts of Escherichia coli and subjected to N-terminal sequence analysis. The 25-residue amino acid sequence obtained was used to design primers for the amplification of the corresponding coding region by the PCR from an E. coli DNA template. A 74-base-pair DNA segment was obtained that matched a region in the pcnB locus of E. coli, a gene that had originally been identified as controlling plasmid copy number [J. Lopilato, S. Bortner & J. Beckwith (1986) Mol. Gen. Genet. 205, 285-290] and was subsequently cloned and sequenced [J. Liu & J. S. Parkinson (1989) J. Bacteriol. 171, 1254-1261]. Direct evidence that the pcnB locus encodes poly(A) polymerase was provided by the observation that a bacterial strain transformed with an inducible expression vector carrying pcnB as a translational fusion produced 100-fold elevated levels of poly(A) polymerase upon induction. No increased poly(A) polymerase activity was observed in cells transformed with expression vectors carrying truncated forms of the pcnB gene. The identification of a gene encoding bacterial poly(A) polymerase opens the way for the study of the biosynthesis and function of bacterial polyadenylylated mRNA. PMID- 1438226 TI - Depth, motion, and static-flow perception at metaisoluminant color contrast. AB - Many experiments concerned with the role of color in depth and motion perception have applied isoluminant random-dot stereograms and cinematograms. The poor performance in the absence of luminance contrast has been associated with color blindness of stereopsis and motion perception (Livingstone, M.S. & Hubel, D.H. (1987) J. Neurosci. 7, 3416-3468). Nevertheless, isoluminant stimuli are not fully accepted as appropriate tools in isolating central mechanisms (Logothetis, N.K., Schiller, P.H., Charles, E.R. & Hurlbert, A.C. (1990) Science 247, 214 217). In our experiments we use a broad luminance range to test whether color can contribute to a given mechanism when luminance contrast is present but has a strong "veto" effect from opposite luminance contrast, a condition we named "metaisoluminance." There is no fusion in stereopsis under polarity reversal, when only luminance information is given, and reversed-phi phenomenon is experienced for motion. As a third "matching" task, we included polarity-reversed random-dot Glass-patterns, which exhibit "static flow" and also show pattern reversal. We found that color can counteract the effects of polarity reversal by restoring stereoscopic fusion and reversed phi motion and does it with increased efficiency as the hue contrast increases. We found no such effect of color in Glass-patterns. Thus, we showed that the visual system for binocular depth and motion perception is not color-blind, although correlated hue information under metaisoluminance does not appear to yield shape perception. PMID- 1438225 TI - Obliterative bronchiolitis after lung transplantation: a fibroproliferative disorder associated with platelet-derived growth factor. AB - Fibroproliferative disorders are characterized by accumulations of mesenchymal cells and connective tissue in critical locations, leading to organ dysfunction. We examined the role of platelet-derived growth factor (PDGF) in the pathogenesis of obliterative bronchiolitis, a fibroproliferative process that occurs after lung transplantation and results in small airway occlusion. Bronchoalveolar lavage fluid from obliterative bronchiolitis patients significantly stimulated fibroblast migration, whereas fluid from patient controls did not. Quantitation by radioligand binding assay demonstrated increased concentrations of PDGF in lavage fluid from obliterative bronchiolitis patients (patients, 104 +/- 26.9 pM; controls, 8.4 +/- 6.9 pM; P < 0.01). Heparin affinity, gel filtration, and Western blot analysis confirmed the presence of PDGF in lavage fluid. Immunohistochemical and in situ hybridization studies of histologic sections and bronchoalveolar lavage cells suggest that alveolar macrophages are one cellular source. Prospective evaluation of sequential bronchoalveolar lavage samples from a patient who developed obliterative bronchiolitis demonstrated markedly increased PDGF concentrations before the onset of irreversible airflow obstruction. These findings are consistent with a role for PDGF in the fibroproliferative changes observed in obliterative bronchiolitis. PMID- 1438227 TI - Regulation of BALB/c 3T3 fibroblast proliferation by B-myb is accompanied by selective activation of cdc2 and cyclin D1 expression. AB - The B-myb gene is expressed in many cell types at the G1/S transition of the cell cycle. Inhibition of B-myb expression in BALB/c 3T3 fibroblasts by introduction of a B-myb antisense construct greatly diminished cell proliferation, whereas constitutive expression of a human B-myb cDNA in these cells reduced their growth factor requirements and induced a transformed phenotype. Constitutive expression of B-myb cDNA was accompanied by activation of cyclin D1 and cdc2 expression but not of cyclin A and cyclin B. Transfection of BALB/B-myb cells (a cell line expressing high levels of exogenous human B-myb) with a cyclin D1 antisense construct drastically reduced cloning efficiency of these cells. These results suggest that the B-myb-encoded product regulates fibroblast proliferation by activating cdc2 and cyclin D1 gene expression and that abnormal expression of cyclin D1 might be a step in the process of transformation. PMID- 1438228 TI - Transplantation tolerance is unrelated to superantigen-dependent deletion and anergy. AB - C57BL/6 (B6; I-E-, Mls-2b) nude mice, reconstituted at birth with thymic epithelium (TE) from BALB/c (BA; I-E+, Mls-2a) day 10 embryos (E10), permanently accepted BALB/c skin, when grafted as adults. T-cell receptor repertoire analyses in the periphery of these mice revealed no difference in frequencies of I E/superantigen-reactive T-cell receptor V beta families, as compared to chimeras constructed with syngeneic B6 E10 TE. T lymphocytes bearing V beta 3, V beta 5, and V beta 11 T-cell receptors, from either allogeneic or syngeneic TE chimeras, responded equally well to in vitro receptor-dependent stimulation. Similar results were obtained with nude mice reconstituted at birth with E14 thymuses, already colonized by hemopoietic cells. These observations indicate that neither TE cells nor the progenies of hemopoietic precursors that colonize the thymus up to E14 express or functionally present the superantigens addressed here; it follows that tolerance to skin grafts and superantigen-related T-cell deletions are unrelated phenomena. PMID- 1438229 TI - Cloning and sequencing of a trophoblast-endothelial-activated lymphocyte surface protein: cDNA sequence and genomic structure. AB - We have previously described the distribution of a surface glycoprotein recognized by monoclonal antibody B721. We now report the molecular characterization of this molecule at the protein, cDNA, and genomic level. A 75 kDa glycoprotein can be immunoprecipitated from B721+ tissues. We have isolated a near full-length cDNA containing the complete coding region and a full-length genomic clone. We present evidence that this protein has similarity to several classes of nuclear transcription factors, particularly the myc family of proteins. The 721P protein was found to have a leucine zipper-like structure, a possible basic region immediately upstream from the leucine zipper, and a protein kinase A phosphorylation site. 721P protein is encoded by a gene distinct from any deposited in existing data bases, and displays several features associated with proteins involved in signal transduction and gene regulation. PMID- 1438230 TI - Chromosomal organization of the heavy chain variable region gene segments comprising the human fetal antibody repertoire. AB - The adult repertoire of antibody specificities is acquired in a developmentally programmed fashion that, in mouse and man, parallels the ordered rearrangement of a limited number of germ-line heavy chain variable region (VH) gene segments during development. It has been hypothesized that this developmental bias is a consequence of gene organization. In the mouse, rearrangement of VH gene segments proximal to the heavy chain joining region (JH) locus precedes rearrangement of genes located more distal to the JH locus. Similarly, in man, two VH elements located proximal to JH are expressed during fetal development. To test further this hypothesis in man, we have determined in a single individual the positions of an additional eight distinct VH elements known to comprise a significant fraction of the human developmental repertoire. These developmentally expressed VH elements were found to be dispersed over a region of 890 kilobases of the VH locus and were interspersed with other VH elements that are not known to be developmentally expressed. Thus, the ordered developmental expression of VH gene segments in man must involve mechanisms beyond physical proximity to the JH locus. Further, these results support the notion that fetal expression of VH gene segments is a regulated process and suggest that this regulation is important in the acquisition of immunocompetence. PMID- 1438231 TI - Functional erythroid promoters created by interaction of the transcription factor GATA-1 with CACCC and AP-1/NFE-2 elements. AB - We have investigated interactions between the erythroid transcription factor GATA 1 and factors binding two cis-acting elements commonly linked to GATA sites in erythroid control elements. GATA-1 is present at all stages of erythroid differentiation, is necessary for erythropoiesis, and binds sites in all erythroid control elements. However, minimal promoters containing GATA-1 sites are inactive when tested in erythroid cells. Based on this observation, two erythroid cis elements, here termed CACCC and AP-1/NFE-2, were linked to GATA sites in minimal promoters. None of the elements linked only to a TATA box created an active promoter, but GATA sites linked to either CACCC or AP-1/NFE-2 elements formed strong erythroid promoters. A mutation of T to C at position -175 in the gamma-globin promoter GATA site, associated with hereditary persistence of fetal hemoglobin (HPFH), increased expression of these promoters in both fetal and adult cells. A construct bearing the beta-globin CACCC element was more active in adult and less active in fetal erythroid cells, when compared with the gamma-globin CACCC element. These studies suggest that erythroid control elements are formed by the interactions of at least three transcription factors, none of which functions alone. PMID- 1438232 TI - Alpha-crystallin can function as a molecular chaperone. AB - The alpha-crystallins (alpha A and alpha B) are major lens structural proteins of the vertebrate eye that are related to the small heat shock protein family. In addition, crystallins (especially alpha B) are found in many cells and organs outside the lens, and alpha B is overexpressed in several neurological disorders and in cell lines under stress conditions. Here I show that alpha-crystallin can function as a molecular chaperone. Stoichiometric amounts of alpha A and alpha B suppress thermally induced aggregation of various enzymes. In particular, alpha crystallin is very efficient in suppressing the thermally induced aggregation of beta- and gamma-crystallins, the two other major mammalian structural lens proteins. alpha-Crystallin was also effective in preventing aggregation and in refolding guanidine hydrochloride-denatured gamma-crystallin, as judged by circular dichroism spectroscopy. My results thus indicate that alpha-crystallin refracts light and protects proteins from aggregation in the transparent eye lens and that in nonlens cells alpha-crystallin may have other functions in addition to its capacity to suppress aggregation of proteins. PMID- 1438233 TI - ATPase activity of transcription-termination factor rho: functional dimer model. AB - Transcription-termination factor rho of Escherichia coli functions as an RNA dependent ATPase that causes transcript release at specific rho-dependent termination sites on the DNA template. Rho exists as a hexagon of identical subunits, physically organized as a trimer of dimers with D3 symmetry. The structural asymmetry of the dimer is reflected in the binding properties of rho; each dimer has a strong and a weak binding site for both the ATP substrate and the RNA cofactor. Here we use homopolynucleotides in competition and complementation experiments to characterize the ATPase activation properties of the cofactor binding sites of the functional rho dimer. We show that (i) no ATPase activity is observed unless both the high- and the low-affinity cofactor binding sites of the functional rho dimer are occupied; (ii) saturating levels of poly(rC), poly(rC) in combination with poly(rU), or poly(rU) alone can fully activate the ATPase of rho; and (iii) poly(dC) can serve as a fully competitive inhibitor of half of the ATPase activity of rho when one of the cofactor sites is filled with poly(rC). These observations lead to a set of phenomenological rules that describe the cofactor dependence of the ATPase activation of the functional dimer of rho and help to define a mechanistic basis for interpreting rho function in termination. PMID- 1438234 TI - CDC46/MCM5, a yeast protein whose subcellular localization is cell cycle regulated, is involved in DNA replication at autonomously replicating sequences. AB - Saccharomyces cerevisiae cells containing mutations in the cell-division-cycle gene CDC46 arrest with a large bud and a single nucleus with unreplicated DNA at the non-permissive temperature. This G1/S arrest, together with the increased rates of mitotic chromosome loss and recombination phenotype, suggests that these mutants are defective in DNA replication. The subcellular localization of the CDC46 protein changes with the cell cycle; it is nuclear between the end of M phase and the G1/S transition but is cytoplasmic in other phases of the cell cycle. Here we show that CDC46 is identical to MCM5, based on complementation analysis of the mcm5-1 and cdc46-1 alleles, complementation of the minichromosome maintenance defect of mcm5-1 by CDC46, and the genetic linkage of these two genes. Like mcm5-1, cdc46-1 and cdc46-5 also show a minichromosome maintenance defect thought to be associated with DNA replication initiation at autonomously replicating sequences. Taken together, these observations suggest that CDC46/MCM5 acts during a very narrow window at the G1/S transition or the beginning of S phase by virtue of its nuclear localization to effect the initiation of DNA replication at autonomously replicating sequences. PMID- 1438235 TI - The (4;11)(q21;q23) chromosome translocations in acute leukemias involve the VDJ recombinase. AB - Chromosomal region 11q23 is frequently rearranged in acute lymphocytic leukemias (ALLs) and in acute myeloid leukemias (AMLs), mostly in reciprocal exchanges with various translocation partners. The most common of these translocations is t(4;11)(q21;q23). It is present in approximately 10% of ALL patients, most frequently in very young children. We have recently cloned a region of chromosome 11, the ALL-1 locus, found to be rearranged in malignant cells from patients with the t(4;11), t(9;11), t(11;19), t(1;11), t(6;11), t(10;11), and del(11q23) chromosomal abnormalities. Here we report the cloning and characterization of chromosomal breakpoints from leukemic cells with t(4;11) aberrations. The breakpoints cluster in regions of 7-8 kilobases on both chromosomes 4 and 11. The presence of heptamer- and nonamer-like sequences at the sites of breakage suggests that the VDJ recombinase utilized for immunoglobulin gene rearrangement is also directly involved in these translocations. We also show that leukemic cells with t(4;11) express altered RNAs transcribed from the derivative chromosomes 11 and 4. PMID- 1438236 TI - Variations in patterns of DNA damage induced in human colorectal tumor cells by 5 fluorodeoxyuridine: implications for mechanisms of resistance and cytotoxicity. AB - We have previously shown that treatment of the HT29 human colorectal tumor (HCT) cell line with 100 nM 5-fluorodeoxyuridine (FdUrd) induces DNA fragments ranging from 50 kilobases to 5 megabases. The studies reported here were conducted to characterize the kinetics, concentration dependence, and pharmacologic specificity of this process and to determine if such fragmentation varies among HCT cell lines. HT29 and SW620 cells yielded similar fragment size distributions upon treatment with either FdUrd or CB3717 [a folate analog inhibitor of thymidylate synthase (TS)]. With either of these agents the SW620 line required higher drug concentrations or longer incubation times than HT29 cells to achieve a given level of fragmentation or cytotoxicity, even though the two cell lines are equally sensitive to FdUrd-induced TS inhibition. These data indicate that SW620 resistance is not due to a lesion in the events leading up to TS inhibition but it may be due to a difference in the steps following TS inhibition. Aphidicolin, a DNA polymerase inhibitor, did not cause substantial fragmentation or cytotoxicity in these two cell lines, demonstrating that the fragmentation response to the other two drugs is not a general consequence of DNA synthesis inhibition. A third HCT line, HuTu80, gave rise only to a smaller and more discrete population of DNA fragments, ranging from approximately 50 to 200 kilobases, following exposure to FdUrd. Similar patterns were seen in this line upon treatment with CB3717 or aphidicolin, indicating that this fragmentation pattern is not specific to TS inhibition and may be characteristic of a more general response than that seen in the other two cell lines. DNA fragments induced by FdUrd in HuTu80 cells did not degrade into smaller pieces, demonstrating that the process by which they are formed is distinct from apoptosis. We conclude that the responses of HCT cells to FdUrd-induced TS inhibition vary significantly, that these differences may reflect heterogeneity in the mechanism of DNA damage formation, and that, in some cases, FdUrd resistance may be due to alterations in the fragmentation process. PMID- 1438237 TI - Supercoiled DNA wraps around the bacteriophage phi 29 head-tail connector. AB - Supercoiled pBR322 DNA wraps around the outside of the isolated Bacillus subtilis bacteriophage phi 29 head-tail connector, the crux of the DNA packaging machine of the viral precursor capsid or prohead. The contour length of the supercoiled DNA, determined by EM, decreased by approximately 180 base pairs for each connector bound. Mass and radial density determinations by scanning transmission EM showed that the increased mass of the connector-DNA complex relative to the connector alone was equivalent to approximately 170 base pairs of DNA and was located around the outside of the connector. Topoisomerase I treatment of the complexes followed by deproteinization suggested that supercoils were restrained by the connectors. Connectors bound linear and open-circular plasmid DNAs inefficiently but were not wrapped by these DNAs. The wrapping of supercoiled DNA around the isolated phi 29 connector is hypothesized to reflect the initiation phase of the normal process of DNA packaging. Packaging substrates would be supercoiled, wrapped by the connector, linearized, and translocated by rotation of the connector relative to the viral capsid with the aid of ATP hydrolysis. PMID- 1438238 TI - Differential regulation of neuropeptide mRNA expression in intrastriatal striatal transplants by host dopaminergic afferents. AB - The effects of dopamine-specific manipulations on neuropeptide gene expression in intrastriatal grafts of fetal striatal tissue were studied by quantitative in situ hybridization histochemistry, using 35S-labeled oligonucleotide probes. Messenger RNA transcripts for the striatal neuropeptides preproenkephalin (PPE) and preprotachykinin (PPT) were detected in neurons forming discrete patches in the striatal grafts. The relative abundance of PPE and PPT mRNA-expressing neurons within the graft patches (51-54%) was similar to that found in normal caudate-putamen. In specimens with intact dopamine afferents the expression of PPE mRNA in grafted neurons was similar to that found in normal caudate putamen, whereas the hybridization signal for PPT mRNA was 27% higher in the graft neurons than in the normal caudate-putamen. Removal of host dopaminergic afferents by 6 hydroxydopamine lesions of the ipsilateral mesostriatal dopamine pathway increased the hybridization signal for PPE mRNA both in the grafts (+84%) and in the spared ipsilateral host caudate-putamen (+125%), whereas the PPT signal was reduced by 53% in the grafts and by 51% in the remaining host caudate-putamen. Similarly, chronic treatment of grafted animals with the dopamine receptor antagonist haloperidol (2 mg/kg per day for 10 days) produced a 146% increase in the PPE signal in the grafts and a 175% increase in the intact contralateral caudate-putamen, whereas the signal for PPT mRNA was again decreased by 52% and 51% in the grafts and host caudate-putamen, respectively. These results show that the host nigrostriatal dopamine pathway differentially regulates enkephalin and substance P gene expression within striatal grafts and thereby exerts a tonic functional influence over grafted striatal neurons. PMID- 1438239 TI - Switch in glutamate receptor subunit gene expression in CA1 subfield of hippocampus following global ischemia in rats. AB - Severe, transient global ischemia of the brain induces delayed damage to specific neuronal populations. Sustained Ca2+ influx through glutamate receptor channels is thought to play a critical role in postischemic cell death. Although most kainate-type glutamate receptors are Ca(2+)-impermeable, Ca(2+)-permeable kainate receptors have been reported in specific kinds of neurons and glia. Recombinant receptors assembled from GluR1 and/or GluR3 subunits in exogenous expression systems are permeable to Ca2+; heteromeric channels containing GluR2 subunits are Ca(2+)-impermeable. Thus, altered expression of GluR2 in development or following a neurological insult or injury to the brain can act as a switch to modify Ca2+ permeability. To investigate the molecular mechanism underlying delayed postischemic cell death, GluR1, GluR2, and GluR3 gene expression was examined by in situ hybridization in postischemic rats. Following severe, transient forebrain ischemia GluR2 gene expression was preferentially reduced in CA1 hippocampal neurons at a time point that preceded their degeneration. The switch in expression of kainate/AMPA receptor subunits coincided with the previously reported increase in Ca2+ influx into CA1 cells. Timing of the switch indicates that it may play a causal role in postischemic cell death. PMID- 1438240 TI - Analogs of palmitoyl-CoA that are substrates for myristoyl-CoA:protein N myristoyltransferase. AB - Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase (Nmt1p; EC 2.3.1.97) is an essential enzyme that is highly selective for myristoyl-CoA in vivo. It is unclear why myristate (C14:0), a rare cellular fatty acid, has been selected for this covalent protein modification over more abundant fatty acids such as palmitate (C16:0), nor is it obvious how the enzyme's acyl-CoA binding site is able to discriminate between these two fatty acids. Introduction of a cis double bond between C5 and C6 of palmitate [(Z)-5-hexadecenoic acid] or a triple bond between C4 and C5 or C6 and C7 (Y4- and Y6-hexadecenoic acids) yields compounds that, when converted to their CoA derivatives, approach the activity of myristoyl-CoA as Nmt1p substrates in vitro. Kinetic studies of 42 C12-C18 fatty acids containing triple bonds, para-phenylene, or a 2,5-furyl group, as well as cis and trans double bonds, suggest that the geometry of the enzyme's acyl-CoA binding site requires that the acyl chain of active substrates assume a bent conformation in the vicinity of C5. Moreover, the distance between C1 and the bend appears to be a critical determinant for optimal positioning of the acyl-CoA in this binding site so that peptide substrates can subsequently bind in the sequential ordered bi-bi reaction mechanism. Identification of active, conformationally restricted analogs of palmitate offers an opportunity to "convert" wild-type or mutant Nmts to palmitoyltransferases so that they can deliver these C16 fatty acids to critical N-myristoylproteins in vivo. nmt181p contains a Gly-451-->Asp mutation, which causes a marked reduction in the enzyme's affinity for myristoyl-CoA. Strains of S. cerevisiae containing nmt1-181 exhibit temperature-sensitive myristic acid auxotrophy: their complete growth arrest at 37 degrees C is relieved when the medium is supplemented with 500 microM C14:0 but not with C16:0. The CoA derivatives of (Z)-5-hexadecenoic and Y6 hexadecynoic acids are as active substrates for the mutant enzyme as myristoyl CoA at 24 degrees C. However, unlike C16:0, they produce growth arrest of nmt181p producing cells at this "permissive" temperature, suggesting that these C16 fatty acids do not allow expression of the biological functions of essential S. cerevisiae N-myristoylproteins. PMID- 1438241 TI - Chimeric gag-V3 virus-like particles of human immunodeficiency virus induce virus neutralizing antibodies. AB - A 41-kDa unprocessed human immunodeficiency virus 2 (HIV-2) gag precursor protein that has a deletion of a portion of the viral protease assembles as virus-like particles by budding through the cytoplasmic membrane of recombinant baculovirus infected insect cells. We have constructed six different combinations of chimeric genes by coupling the truncated HIV-2 gag gene to the neutralizing domain (V3) or the neutralizing and the CD4 binding domains (V3+CD4BD) of gp120 env gene sequences from HIV-1 or HIV-2. The env gene sequences were inserted either into the middle of the gag gene or at the 3' terminus of the gag gene. Virus-like particles were formed by chimeric gene products only when the env gene sequences were linked to the 3' terminus of the gag gene. Insertion of env gene sequence in the middle of the gag gene resulted in high-level chimeric gene expression but without the formation of virus-like particles. Three different chimeric genes [gag gene with HIV-1 V3 (1V3), gag gene with HIV-2 V3 (2V3), and gag gene with HIV-2 V3+CD4BD (2V3+CD4BD)] formed virus-like particles that were secreted into the cell culture medium. In contrast, the HIV-1 V3+CD4BD/HIV-2 gag construct did not form virus-like particles. The chimeric gag-env particles had spherical morphology and the size was slightly larger than that of the gag particles, but the chimeric particles were similar to the mature HIV particles. Western blot analysis showed that the gag-env chimeric proteins were recognized by antibodies in HIV-positive human serum and rabbit anti-gp120 serum. Rabbit anti-gag 1V3 and anti-gag 2V3 sera reacted with authentic gp120 of HIV-1 and HIV-2, respectively, and neutralized homologous HIV infectivity. Our results show that precursor gag protein has potential as a carrier for the presentation of foreign epitopes in good immunological context. The gag protein is highly immunogenic and has the ability to carry large foreign inserts; as such, it offers an attractive approach for HIV vaccine development. PMID- 1438242 TI - Construction and characterization of chimeric tick-borne encephalitis/dengue type 4 viruses. AB - Dengue type 4 virus (DEN4) cDNA was used as a vector to express genes of the distantly related tick-borne encephalitis virus (TBEV). Full-length chimeric TBEV/DEN4 cDNAs were constructed by substituting TBEV genes coding for proteins such as capsid (C); pre-membrane, which is the precursor of membrane (M); envelope (E); or nonstructural protein NS1 for the corresponding DEN4 sequences. RNA transcripts prepared from cDNAs were used to transfect permissive simian cells. Two viable chimeric viruses that contained TBEV CME or ME genes were recovered. Compared with DEN4, chimeric TBE(ME)/DEN4 virus [designated vTBE(ME)/DEN4] produced larger plaques and grew to higher titer in simian cells. In contrast, vTBE(ME)/DEN4 produced smaller plaques on mosquito cells and grew to lower titer than DEN4. Analysis of viral RNA and proteins produced in vTBE(ME)/DEN4- and DEN4-infected mosquito or simian cells revealed that the chimera was restricted in its ability to enter and replicate in mosquito cells. In contrast, vTBE(ME)/DEN4 entered simian cells efficiently and its RNA was replicated more rapidly in these cells than was parental DEN4 RNA. Following intracerebral inoculation, vTBE(ME)/DEN4 caused fatal encephalitis in both suckling and adult mice, while nearly all mice inoculated by the same route with DEN4 did not develop disease. Unlike wild-type TBEV, vTBE(ME)/DEN4 did not cause encephalitis when adult mice were inoculated by a peripheral route. Adult mice previously inoculated with the chimera by a peripheral route were completely resistant to subsequent intraperitoneal challenge with 10(3) times the median lethal dose of TBEV, whereas mice previously inoculated with DEN4 were not protected. These findings indicate that (i) the TBEV M and E genes of the chimeric virus are major protective antigens and induce resistance to lethal TBEV challenge and (ii) other regions of the TBEV genome are essential for the ability of this virus to spread from a peripheral site to the brain. Success in constructing a viable TBEV/DEN4 chimera that retains the protective antigens of TBEV but lacks its peripheral invasiveness provides a strategy for the development of live attenuated TBEV vaccines. PMID- 1438243 TI - A synthetic peptide inhibitor of human immunodeficiency virus replication: correlation between solution structure and viral inhibition. AB - A peptide designated DP-107 was synthesized containing amino acid residues 558 595 of the envelope glycoprotein gp160 of human immunodeficiency virus type 1 strain LAI (HIV-1LAI). Algorithms for secondary structure have predicted that this region of the envelope transmembrane protein should form an extended alpha helix. Consistent with this prediction, analysis by circular dichroism (CD) indicated that, under physiological conditions, DP-107 is approximately 85% helical. The high degree of stable secondary structure in a synthetic peptide of this size suggests self-association typical of a coiled coil or leucine zipper. In biological assays, the peptide efficiently blocked virus-mediated cell-cell fusion processes as well as infection of peripheral blood mononuclear cells by both prototypic and primary isolates of HIV-1. A single amino acid substitution in the peptide greatly destabilized its solution structure as measured by CD and abrogated its antiviral activity. An analogue containing a terminal cysteine was oxidized to form a dimer, and this modification lowered the dose required for antiviral effect from 5 to about 1 microgram/ml. These results suggest that both oligomerization and ordered structure are necessary for biological activity. They provide insights also into the role of this region in HIV infection and the potential for development of a new class of antiviral agents. PMID- 1438244 TI - High- and low-affinity binding of GRO alpha and neutrophil-activating peptide 2 to interleukin 8 receptors on human neutrophils. AB - GRO alpha and neutrophil-activating peptide 2 (NAP-2), like their analog interleukin 8 (IL-8), are considered to be inflammatory mediators since they recruit and activate neutrophil leukocytes. After introduction of tyrosines by substitution for other residues at the C terminus, GRO alpha and NAP-2 were labeled with 125I and used for binding studies. A total of 60,000-90,000 receptors per neutrophil were found for either ligand. Of these 30-45% were of high affinity with a mean Kd value of 0.3 and 0.7 nM for GRO alpha and NAP-2, respectively, and 55-70% of low affinity (Kd = 30 nM). Two proteins of approximately 70 kDa and 44 kDa (p70 and p44) were specifically cross-linked with labeled GRO alpha, NAP-2, and IL-8. Unlabeled IL-8 fully inhibited this cross linking and the binding of labeled GRO alpha or NAP-2 to the high-affinity sites on neutrophils or neutrophil membranes. Treatment of membranes with digitonin resulted in the preferential solubilization of a single receptor species, corresponding to p44, that bound GRO alpha and NAP-2 with low affinity (Kd = 30 nM) and IL-8 with high affinity (Kd = 0.4 nM). Exposure of neutrophil membranes to 100 microM guanosine 5'-[gamma-thio]triphosphate led to a 75-fold increase of the Kd in approximately 60% of the IL-8 receptors. High-affinity receptors for GRO alpha and NAP-2 were similarly affected. In contrast, guanosine 5'-[gamma thio]triphosphate had no effect on the binding of IL-8 to p44 solubilized by digitonin. These results demonstrate that human neutrophils bear two classes of receptors for GRO alpha, NAP-2, and IL-8 (p70 and p44) that may differ in their mode of interaction with GTP regulatory proteins. PMID- 1438245 TI - Functional interactions between putative intramembrane charged residues in the lactose permease of Escherichia coli. AB - Using a lactose permease mutant devoid of Cys residue ("C-less permease"), we systematically replaced putative intramembrane charged residues with Cys. Individual replacements for Asp-237, Asp-240, Glu-269, Arg-302, Lys-319, His-322, Glu-325, or Lys-358 abolish active lactose transport. When Asp-237 and Lys-358 are simultaneously replaced with Cys and/or Ala, however, high activity is observed. Therefore, when either Asp-237 or Lys-358 is replaced with a neutral residue, leaving an unpaired charge, the permease is inactivated, but neutral replacement of both residues yields active permease [King, S. C., Hansen, C. L. & Wilson, T. H. (1991) Biochim. Biophys. Acta 1062, 177-186]. Remarkably, moreover, when Asp-237 is interchanged with Lys-358, high activity is observed. The observations provide a strong indication that Asp-237 and Lys-358 interact to form a salt bridge. In addition, the data demonstrate that neither residue nor the salt bridge plays an important role in the transport mechanism. Thirteen additional double mutants were constructed in which a negative and a positively charged residue were replaced with Cys. Only Asp-240-->Cys/Lys-319-->Cys exhibits significant activity, accumulating lactose to 25-30% of the steady state observed with C-less permease. Replacing either Asp-240 or Lys-319 individually with Ala also inactivates the permease, but double mutants with neutral substitutions (Cys and/or Ala) at both positions exhibit essentially the same activity as Asp-240- >Cys/Lys-319-->Cys. In marked contrast to Asp-237 and Lys-358, interchanging Asp 240 and Lys-319 abolishes active lactose transport. The results demonstrate that Asp-240 and Lys-319, like Asp-237 and Lys-358, interact functionally and may form a salt bridge. However, the interaction between Asp-240 and Lys-319 is clearly more complex than the interaction between Asp-237 and Lys-358. In any event, the findings suggest that putative transmembrane helix VII lies next to helices X and XI in the tertiary structure of lactose permease. PMID- 1438246 TI - Homozygous deletions within human chromosome band 9p21 in melanoma. AB - Genetic studies have implicated the early involvement of a gene on chromosome arm 9p in the development of cutaneous melanoma. We have performed loss-of heterozygosity studies to confirm these original findings and identify the most frequently rearranged or deleted region of 9p. Eight markers were analyzed, including (from 9pter to proximal 9q) D9S33, the beta-interferon (IFNB1) locus, the alpha-interferon (IFNA) gene cluster, D9S126, D9S3, D9S19, the glycoprotein 4 beta-galactosyltransferase (GGTB2) gene, and the argininosuccinate synthetase pseudogene 3 (ASSP3). Two or more of these loci were found to be hemizygously reduced in 12 of 14 (86%) informative metastatic melanoma tumor and cell line DNAs, and homozygous deletions of the marker D9S126 were observed in 2 of 20 (10%) melanoma cell lines. These findings have resulted in the identification of a small critical region of 2-3 megabases on 9p21 in which a putative melanoma tumor-suppressor gene appears likely to reside. Several 9p candidate genes, including IFNB1, the IFNA gene cluster, GGTB2, and the tyrosinase-related protein (TYRP) locus, have all been eliminated as potential targets because they are located outside of the homozygously deleted regions. PMID- 1438247 TI - Construction of chimeric vaccinia viruses by molecular cloning and packaging. AB - Foreign DNA was inserted into unique restriction endonuclease cleavage sites (Sma I or Not I) of the 200,000-base-pair vaccinia virus genome by direct molecular cloning. The modified vaccinia virus DNA was packaged in fowlpox virus-infected avian cells, and chimeric vaccinia virus was isolated from mammalian cells not supporting the growth of the fowlpox helper virus. In contrast to the classical "in vivo" recombination technique, chimeric viruses with inserts in both possible orientations and families of chimeras with multiple inserts were obtained. The different genomic configurations of chimeric viruses provide a broader basis for screening of optimal viruses. In addition to packaging in avian cells, a second packaging procedure for vaccinia DNA, based on the abortive infection of mammalian cells with the fowlpox helper virus, was developed. This procedure permits simultaneous packaging and host-range selection for the packaged virus. The cloning/packaging procedure allows the direct insertion of foreign DNA without the need for plasmids having flanking regions homologous to viral nonessential regions and is independent of inefficient in vivo recombination events. By direct cloning and packaging, about 5-10% of the total vaccinia virus yield consisted of chimeras. The procedure is, therefore, a useful tool in molecular virology. PMID- 1438248 TI - Distribution of mRNA of a Na(+)-independent neutral amino acid transporter cloned from rat kidney and its expression in mammalian tissues and Xenopus laevis oocytes. AB - The Na(+)-independent neutral amino acid transporter (NAA-Tr) that we had previously cloned from rat kidney has been investigated with respect to its distribution in mammalian tissues and cells. By Northern blot analysis and RNase protection assay, a 2.4-kilobase (kb) mRNA in rat intestine was found to be identical to that in rat kidney. Of the other rat tissues examined, only brain and heart were found to contain mRNAs related to kidney NAA-Tr by Northern assay. However, these were larger (approximately 5 and approximately 7 kb). Mouse and rabbit kidney also contain mRNAs of 2.4 kb that exhibited a high degree of homology with rat kidney NAA-Tr. Of the several cultured cells investigated that demonstrated considerable Na(+)-independent neutral amino acid transport activity, only human colon carcinoma (Caco) cells were positive by Northern assay. The failure to detect NAA-Tr mRNA in many cells and tissues that carry out Na(+)-independent transport indicates that unrelated transporters must also exist. Cells and tissues that were negative with respect to rat kidney NAA-Tr as well as those that were positive transported leucine and tryptophan equally well. However, when mRNA from the same cells and tissues was expressed in oocytes, in all cases tryptophan was transported far less efficiently than leucine. This defect in tryptophan transport is apparently due to aberrant expression of neutral amino acid transporters in general in Xenopus oocytes. PMID- 1438249 TI - Persistence of Ha-ras-induced metastatic potential of SP1 mouse mammary tumors despite loss of the Ha-ras shuttle vector. AB - Previous studies have shown that the SP1 mouse mammary adenocarcinoma cell line, which is tumorigenic but nonmetastatic, acquires metastatic potential when transfected with the activated human Ha-ras gene. In addition, the process of calcium phosphate-mediated DNA transfection, as well as treatment with the calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, can also result in heritable changes in the malignant behavior of SP1 cells. It was of interest, therefore, to determine whether the metastatic consequences of Ha-ras oncogene expression in SP1 cells are a primary effect of the transfected gene or whether heritable secondary changes are induced by Ha-ras oncogene expression. In the latter case, continued expression of the Ha-ras oncogene would not be required to maintain the metastatic phenotype. To test this hypothesis we introduced the Ha ras oncogene into SP1 cells on a shuttle vector in which maintenance of the vector was dependent on selection for resistance to the antibiotic G418. Subclones which had lost the transfected Ha-ras gene were subsequently isolated following growth in nonselective medium. The Ha-ras-transfected clones and the revertant subclones were found to be equally metastatic, indicating that transfection with the Ha-ras gene does induce stable secondary changes in the metastatic phenotype of SP1 cells. PMID- 1438250 TI - Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line. AB - We have isolated a lymphoid cell line, MDS, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines, MDS-T, by transfecting MDS cells with pHXBc2, and MDS-I, by infecting MDS cells with HIV-1IIIB. In 24 hr, 1 x 10(5) MDS-T or MDS-I cells produce 46 ng of p24 per ml and reverse transcriptase that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in MDS-T and MDS-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the MDS cells with the anti-CD4 antibody Leu 3a. For over a year MDS-T and MDS-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the MDS cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12 myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of reverse transcriptase production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication. PMID- 1438251 TI - Identification of a negative regulatory function for steroid receptors. AB - This report describes the identification of a negative regulator of estrogen and progesterone receptor function. Using a reconstituted estrogen-responsive transcription system in Saccharomyces cerevisiae, we have identified a "repressor function," which when mutated, increases the transcriptional activity of the estrogen and progesterone receptors. In the case of the estrogen receptor this mutation increases the sensitivity of estrogen-mediated activation by at least four orders of magnitude. Analysis of derivatives of the estrogen receptor indicated that this repressor specifically affects the transcription activity of the TAF1 activation domain of the estrogen receptor. The repressor was cloned by complementation and identified as SSN6, a previously described mediator of glucose repression in yeast. Our results indicate that SSN6 is likely to be involved also in the repression of other cellular activators. Interestingly, deletion of the SSN6 protein allows the antiestrogens ICI 164384 and nafoxidine to behave as more potent agonists of estrogen receptor function, while RU486 also becomes a more potent activator of progesterone receptor function. These data suggest that in wild-type cells the role of hormone is twofold: it promotes DNA binding of the receptor and it also induces a conformational change in the receptor which overcomes the effects of this repressor function. PMID- 1438252 TI - SpCOUP-TF: a sea urchin member of the steroid/thyroid hormone receptor family. AB - Embryonic nuclear proteins from the sea urchin Strongylocentrotus purpuratus bind in vitro to a cis-acting element that lies upstream of the actin gene CyIIIb and consists of two direct repeats homologous to steroid hormone response elements. This sea urchin element is specifically recognized by transcription factor COUP TF from HeLa cell nuclear extracts as well. A sea urchin gene homologous to the human COUP-TF1 gene was detected by blot hybridization to S. purpuratus genomic DNA. Screening of a genomic DNA library with a human COUP-TF1 cDNA probe produced overlapping genomic clones that carry the S. purpuratus gene. Our results indicate that the sea urchin homologue has a structure similar to the human COUP TF1 gene, i.e., conserved intron positions characteristic of this subgroup of steroid hormone receptors. Sequencing of the exons that encode the DNA- and ligand-binding domains of the sea urchin protein revealed 96% and 92% amino acid identity to the domains of the human protein, respectively. Transcripts derived from the S. purpuratus COUP-TF homologous gene were detected in ovarian and embryonic RNAs from various stages. PMID- 1438253 TI - Phosphatic shell plate of the barnacle Ibla (Cirripedia): a bone-like structure. AB - The carbonate apatite crystals and the segmented structure of the shell plates of the barnacles in the genus Ibla distinguish them from the shell plates of all other barnacles, which are coherent calcitic structures. A detailed study of the hierarchical organization of one of the two shell plate types, the tergum, reveals a remarkably complex structure. Cylinders composed of a chitin-protein complex and nodes of plate-shaped crystals constitute the basic building blocks. The crystals are organized into layered stacks in which the c crystallographic axes are all aligned perpendicular to a 25-nm banded structure. The cylinders are, in turn, ordered in arrays such that parts of each cylinder are aligned in a plane, and parts form arcuate out-of-plane structures. The overall result is a lamellar structure, with a plywood-like motif, that is present throughout an individual segment. A series of segments forms an interlocking mineralized core, which is enclosed within a thick organic envelope. The flexible and complex skeletal structure of the tergum shows some marked similarities to the structure of lamellar bone. Although this is undoubtably a product of convergent evolution, the iblid tergum provides a unique perspective on bone structure, which was heretofore unavailable. PMID- 1438254 TI - Genetic differences at four DNA typing loci in Finnish, Italian, and mixed Caucasian populations. AB - Highly polymorphic segments of the human genome containing variable numbers of tandem repeats (VNTRs) have been widely used to establish DNA profiles of individuals for use in forensics. Methods of estimating the probability of occurrence of matching DNA profiles between two randomly selected individuals have been subject to extensive debate regarding the possibility of significant substructure occurring within the major races. We have sampled two Caucasian subpopulations, Finns and Italians, at four commonly used VNTR loci to determine the extent to which the subgroups differ from each other and from a mixed Caucasian database. The data were also analyzed for the occurrence of linkage disequilibrium among the loci. The allele frequency distributions of some loci were found to differ significantly among the subpopulations in a manner consistent with population substructure. Major differences were also found in the probability of occurrence of matching DNA profiles between two individuals chosen at random from the same subpopulation. With respect to the Finnish and Italian subpopulations, the conventional product rule for estimating the probability of a multilocus VNTR match using a mixed Caucasian database consistently yields estimates that are artificially small. Systematic errors of this type were not found using the interim ceiling principle recently advocated in the National Research Council's report [National Research Council (1992) DNA Technology in Forensic Science (Natl. Acad. Sci., Washington)]. The interim ceiling principle is based on currently available racial or ethnic databases and sets an arbitrary lower limit on each VNTR allele frequency. In the future the ceiling frequencies are expected to be established from more adequate data acquired for relevant VNTR loci from multiple subpopulations. PMID- 1438255 TI - Eggs, enzymes, and evolution: natural genetic variants change insect fecundity. AB - Phosphoglucose isomerase genotypes in the butterfly Colias differ dramatically in biochemical properties. These differences were evaluated earlier, using metabolic network theory, to predict, successfully, their effects on glycolytic metabolism and hence on Colias flight capacity and several consequent fitness components in the wild. Female egg-laying, not previously studied, also depends on flight, so female fecundity is now predicted to differ among these genotypes. An experimental design incorporating the thermal ecology of Colias confirms these predictions in a cool habitat. Thus female fecundity differences among animal enzyme polymorphs have now been found. Quantitative reconstruction of the selection regime for phosphoglucose isomerase genotypes in Colias can now begin. The most heat-stable genotypes are the least fecund, suggesting that global warming, if it occurs, may have severe impacts, through population genetics, on demography of thermally sensitive creatures. PMID- 1438256 TI - Calyculin A induces contractile ring-like apparatus formation and condensation of chromosomes in unfertilized sea urchin eggs. AB - Calyculin A, a protein phosphatase inhibitor, induced cleavage-like morphological change in unfertilized sea urchin eggs. A contractile ring-like apparatus containing both filamentous actin and myosin was formed in the cleavage furrow. Wheat germ agglutinin receptors were also found in the same region. The eggs did not develop further after constriction of the ring. No aster-like microtubular structure was found in the calyculin A-treated eggs. The cleavage was not inhibited by the antimicrotubule drug griseofulvin. Calyculin A also increased histone H1 kinase activity and induced chromosome condensation. These changes also occurred in the presence of emetine (an inhibitor of protein synthesis) and aphidicolin (an inhibitor of DNA synthesis). It is suggested that calyculin A induced these changes in the sea urchin eggs by inhibiting the activity of protein phosphatase 1. PMID- 1438257 TI - Activation of the beta-globin locus control region precedes commitment to the erythroid lineage. AB - The beta-globin locus control region (LCR) is characterized by erythroid-specific DNase I hypersensitive sites and is involved in the chromatin organization, transcriptional potentiation, developmental regulation, and replication timing of the entire beta-globin gene cluster. When and how the LCR is first activated during erythropoiesis is not known. Here we analyze the chromatin structure of the LCR during early hematopoietic differentiation using nontransformed, multipotential, growth factor-dependent, murine hematopoietic progenitor cells. We show that LCR hypersensitive sites characteristic of erythroid cells are present in three independent multilineage progenitors [FDCP (factor-dependent cell, Paterson)-mix A4, B6SUtA, and LyD9] under conditions of self-renewal. Induction of differentiation down a nonerythroid pathway causes a progressive loss of hypersensitivity in the LCR. These results show that the beta-globin LCR is in an active chromatin configuration prior to erythroid commitment and indicate a significant role for selective gene repression in lineage specification. PMID- 1438258 TI - Activation of kappa B-specific proteins by estradiol. AB - The kappa B enhancer serves as a recognition site for the nuclear transcription factor NF-kappa B and other kappa B-specific proteins which are activated in many cell types in response to a variety of extracellular signals. But a steroid dependent activation of NF-kappa B or any other kappa B-specific protein has not previously been reported, to our knowledge. In this report we demonstrate that estrogen can activate kappa B-specific protein in its target tissue, uterus. We have done this by analyzing the interaction of nuclear extracts with kappa B enhancers, using DNA mobility shift assays. The activation by estradiol was time dependent, reaching a maximum at approximately 2 hr after steroid treatment, and was not inhibited by prior cycloheximide treatment. The protein-DNA complexes formed in response to estradiol did not contain NF-kappa B and, when compared with other kappa B enhancer motifs, had a higher affinity to the kappa B enhancer corresponding to the PRDII element present in duplicate motifs. These protein-DNA complexes also did not appear to contain estrogen receptor, since antibodies to estrogen receptor were without any effect on either their formation or their mobility. The protein-DNA complexes formed in response to estradiol, however, exhibited a high affinity for the estrogen-responsive element, suggesting the participation of an estrogen-receptor-like molecule in the DNA binding. In contrast, the protein-DNA complexes formed constitutively contained NF-kappa B, had equivalent affinities to various kappa B enhancers, and did not have a high affinity for the estrogen-responsive element. On the basis of these findings, we propose that estrogen-dependent activation of the as-yet-unidentified kappa B specific protein involves the association of this protein with an estrogen receptor-related molecule and binding of the resulting complex to PRDII. The high affinity and specificity of this binding to PRDII suggests that this may serve as a composite regulatory element in mediating estrogen-dependent gene expression. The potential significance of such a mechanism for steroid hormone action is discussed. PMID- 1438259 TI - Roles of bacteriophage T7 gene 4 proteins in providing primase and helicase functions in vivo. AB - The helicase and primase activities of bacteriophage T7 are distributed between the 56- and 63-kDa gene 4 proteins. The 56-kDa gene 4 protein lacks 63 amino acids found at the N terminus of the colinear 63-kDa protein and catalyzes helicase activity. The 63-kDa gene 4 protein catalyzes both primase and helicase activities. A bacteriophage deleted for gene 4, T7 delta 4-1, has been tested for growth by complementation on Escherichia coli strains that contain plasmids expressing either one or both of the gene 4 proteins. T7 delta 4-1 cannot grow (efficiency of plating, 10(-7)) on E. coli cells that express only 56-kDa gene 4 protein. In contrast, T7 delta 4-1 has an efficiency of plating of 0.1 on an E. coli strain that expresses only 63-kDa gene 4 protein in which glycine is substituted for methionine at position 64. A bacteriophage, T7 4B-, in which methionine at residue 64 is replaced by glycine, expresses only 63-kDa gene 4 protein. The burst sizes, latency periods, and Okazaki fragment sizes of T7 4B- are similar in the presence and absence of the 56-kDa gene 4 protein; however, T7 4B- has a reduced rate of DNA synthesis when compared with a phage that synthesizes both gene 4 proteins. PMID- 1438260 TI - Extreme clonal diversity and divergence in populations of a selfing hermaphroditic fish. AB - Recombination is unknown in natural populations of Rivulus marmoratus, a selfing hermaphrodite, and genetic variation is likely due to mutation alone. DNA fingerprinting with an array of microsatellite [e.g., (CT)9] and minisatellite (e.g., the 33.15 core sequence) probes reveals very high clonal diversity within samples of seven Floridian populations, of which five contain about as many clones as there are individuals. There are 42 clones among 58 individuals surveyed (mean, 1.4 individuals per clone), a level of genetic diversity unprecedented among clonal animals. Moreover, all of the probes recognize the same clones even though, at high hybridization stringencies, there is little overlap in the fingerprint patterns they generate. This suggests that most sympatric clones differ by multiple and independent mutational steps. In one population studied in detail, the average number of mutational steps separating two clones is estimated at 9 or 10 and may be substantially higher. The mutational discontinuities among sympatric clones make it unlikely that they evolved by accumulation of neutral mutations in populations that are otherwise genetically uniform. The data argue that the mixing of unrelated individuals from different local populations occurs to an extent previously unappreciated and/or that divergence of clones is mediated by natural selection. If confirmed, the latter would be a serious challenge to current ideas on the predominant role of recombination in promoting the evolution of biological novelty. PMID- 1438261 TI - Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. AB - Most cases of selective IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) occur sporadically. However, familial clustering is not uncommon, and the two disorders can occur within the same family. We have previously described positive associations with three DR-DQ haplotypes as well as a strong negative association with DRw15,DQw6,Dw2 in IgA-D. Different amino acids at position 57 of the HLA-DQ beta chain were found to be related to susceptibility and resistance to IgA-D. Now we have found identical, although somewhat weaker, positive and negative DR-DQ associations in a large group of CVID patients (n = 86), as well as the same associations with codon 57 of the DQB1 gene. In addition, we have confirmed our earlier observations in an independent group of IgA-D individuals (n = 69), and in sib-pair analysis we have found linkage of the genetic susceptibility to IgA-D to the HLA class II region. In IgA-D individuals not carrying the three overrepresented DR-DQ haplotypes, the same positive association with a non-aspartic acid residue at position 57 of the HLA-DQ beta chain was seen. The previously reported associations with deletions of the HLA class III genes C4A (fourth component of complement) and CYP21P (steroid 21-hydroxylase pseudogene) were, in our groups of immunodeficient individuals, statistically secondary to the association with the DQB1 allele 0201. The shared HLA class II associations in the two humoral immunodeficiencies support the hypothesis that IgA-D and CVID are related disorders. Disease susceptibility and resistance are most closely associated with a gene(s) within the DR-DQ region, alleles of the DQB1 locus being candidate genes. PMID- 1438262 TI - A recombinant, soluble, single-chain class I major histocompatibility complex molecule with biological activity. AB - Heterodimeric class I major histocompatibility complex molecules, which consist of a 45-kDa heavy-chain and a 12-kDa beta 2-microglobulin (beta 2m) light chain, bind endogenously synthesized peptides for presentation to antigen-specific T cells. We have synthesized a gene encoding a single-chain, soluble class I molecule derived from mouse H-2Dd, in which the carboxyl terminus of beta 2m is linked via a peptide spacer to the amino terminus of the heavy chain. The chimeric protein is secreted efficiently from transfected L cells, is thermostable, and when loaded with an appropriate antigenic peptide, stimulates an H-2Dd-restricted antigen-specific T-cell hybridoma. Thus, functional binding of peptide does not require the complete dissociation of beta 2m, implying that a heavy chain/peptide complex is not an obligate intermediate in the assembly of the heavy-chain/beta 2m/peptide heterotrimer. Single-chain major histocompatibility complex molecules uniformly loaded with peptide have potential uses for structural studies, toxin or fluor conjugates, and vaccines. PMID- 1438263 TI - Intrahypothalamic injection of a cell line secreting gonadotropin-releasing hormone results in cellular differentiation and reversal of hypogonadism in mutant mice. AB - GT1 is an immortalized cell line that synthesizes and secretes the neurohormone gonadotropin-releasing hormone (GnRH). We have placed these cells into the brains of adult mutant hypogonadal (hpg) mice, which lack a functional GnRH gene, to determine whether such cells could differentiate in situ and support gonadal development. Immunocytochemical detection of GnRH revealed that these cells migrated widely in the central nervous system and elaborated axonal processes which on rare occasion projected to the normal target, the median eminence. Using a battery of antibodies, we demonstrated that these cells could cleave the GnRH precursor and that the amidated decapeptide as well as other cleavage products were present. The presence of biologically active material and its appropriate secretion were further documented by gonadal growth in both males and females. The morphological differentiation of the GT1 cells correlated with the density of cells injected. Those remaining within the injection site and/or forming a tumor retained a simple, rounded or fibroblastic appearance. Those cells that migrated into the host away from such tumors assumed the simple fusiform shape of normal GnRH neurons with dendrites extending from one or both poles. When cell density was drastically reduced a much more complex dendritic arbor was elaborated. These data suggest that such cell lines can be useful in reversing genetic defects and in studying such processes as GnRH neuronal migration, axonal targeting, and cytological differentiation. PMID- 1438264 TI - Role of the 21-kDa protein TIMP-3 in oncogenic transformation of cultured chicken embryo fibroblasts. AB - The 21-kDa protein is an extracellular matrix (ECM) component whose synthesis is stimulated transiently during oncogenic transformation of chicken embryo fibroblasts (CEF) or after treatment of normal cells with the tumor promoter phorbol 12-myristate 13-acetate. Biochemical characterization indicates that the protein is related, but not identical, to two members of the family of tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2. The cDNA of the 21-kDa protein was recently cloned, and based upon its deduced amino acid sequence and other supporting data we propose that it is another member of this family, a TIMP 3. We now report electrophoretic purification of sufficient quantities of this protein to determine its function. The protein promotes the detachment of transforming cells from the ECM. Although its presence in the matrix may be necessary for cell release it is not the only factor involved because it does not influence the adhesive properties of nontransformed cells. It also appears to accelerate the morphological changes associated with cell transformation and stimulates the proliferation of growth-retarded, nontransformed cells maintained under low serum conditions. Based on these data we hypothesize that the 21-kDa protein promotes the development of the transformed phenotype in cultured cells. PMID- 1438265 TI - Analysis of Escherichia coli beta-galactosidase expression in transgenic mice by flow cytometry of sperm. AB - Alterations to the mammalian genome that occur during the development of germ cells, in particular during meiosis, can be introduced into the population upon fertilization. These alterations can occur through homologous recombination, genome rearrangement, or mutagenesis. Such events usually occur infrequently for any particular sequence. Because of the difficulty in analyzing a large number of offspring in a mammalian cross, we have developed a marker to detect these events in sperm, since a large number of these meiotic progeny are produced during male gametogenesis. We have expressed the Escherichia coli lacZ gene during spermatogenesis in transgenic mice and quantitated the levels of beta galactosidase activity in single sperm with the fluorescence-activated cell sorter and a fluorogenic substrate, 5-dodecanoylaminofluorescein di-beta-D galactopyranoside. Detection of rare positives was demonstrated in mixed sperm populations with as few as 0.01% positive sperm. Although the distribution of beta-galactosidase activity in caudal epididymal sperm populations is bimodal, it appears that beta-galactosidase, like other proteins that have been expressed postmeiotically, is distributed between transgene-positive and transgene-negative sperm. PMID- 1438266 TI - Preferential repair of cyclobutane pyrimidine dimers in the transcribed strand of a gene in yeast chromosomes and plasmids is dependent on transcription. AB - While preferential repair of the transcribed strands within active genes has been demonstrated in organisms as diverse as humans and Escherichia coli, it has not previously been shown to occur in chromosomal genes in the yeast Saccharomyces cerevisiae. We found that repair of cyclobutane pyrimidine dimers in the transcribed strand of the expressed RPB2 gene in the chromosome of a repair proficient strain is much more rapid than that in the nontranscribed strand. Furthermore, a copy of the RPB2 gene borne on a centromeric ARS1 plasmid showed the same strand bias in repair. To investigate the relation of this strand bias to transcription, we studied repair in a yeast strain with the temperature sensitive mutation, rpb1-1, in the largest subunit of RNA polymerase II. When exponentially growing rpb1-1 cells are shifted to the nonpermissive temperature, they rapidly cease mRNA synthesis. At the permissive temperature, both rpb1-1 and the wild-type, parental cells exhibited rapid, proficient repair in the transcribed strand of chromosomal and plasmid-borne copies of the RPB2 gene. At the nonpermissive temperature, the rate of repair in the transcribed strand in rpb1-1 cells was reduced to that in the nontranscribed strand. These findings establish the dependence of strand bias in repair on transcription by RNA polymerase II in the chromosomes and in plasmids, and they validate the use of plasmids for analysis of the relation of repair to transcription in yeast. PMID- 1438267 TI - Slp is an essential component of an EDTA-resistant activation pathway of mouse complement. AB - Slp (sex-limited protein) is a mouse serum protein encoded by a major histocompatibility complex class III gene. It is considered to be a product of a duplicated complement component C4 gene, but without functional activity. Originally it has been found expressed only in adult males with the S region of the H-2d or H-2s haplotype. In this report we present evidence that Slp is involved in a form of mouse complement activation that occurs after fractionation of serum by polyethylene glycol precipitation. This activation pathway is EDTA resistant (i.e., independent of classical and alternative pathway activation), is regulated by C1 inhibitor, and leads to the generation of hemolytically active membrane attack complexes. A positive correlation between this EDTA-resistant mouse complement activity and reported Slp levels was found. Direct evidence for a functional role of Slp came from substitution experiments in which purified Slp induced hemolytic activity in polyethylene glycol-fractionated, Slp-deficient mouse serum. Selective depletion of other complement components suggested a role for C1s-, C2, and C5, but not C3, in the Slp-dependent complement activation. A model for this type of mouse complement activation is presented. PMID- 1438268 TI - Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids. AB - We recently reported the discovery of a series of bioactive prostaglandin F2-like compounds (F2-isoprostanes) that are produced in vivo by free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. Inasmuch as phospholipids readily undergo peroxidation, we examined the possibility that F2-isoprostanes may be formed in situ on phospholipids. Initial support for this hypothesis was obtained by the finding that levels of free F2 isoprostanes measured after hydrolysis of lipids extracted from livers of rats treated with CCl4 to induce lipid peroxidation were more than 100-fold higher than levels in untreated animals. Further, increased levels of lipid-associated F2-isoprostanes in livers of CCl4-treated rats preceded the appearance of free compounds in the circulation, suggesting that the free compounds arose from hydrolysis of peroxidized lipids. This concept was supported by demonstrating that free F2-isoprostanes were released after incubation of lipid extracts with bee venom phospholipase A2 in vitro. When these lipid extracts were analyzed by HPLC, fractions that yielded large quantities of free F2-isoprostanes after hydrolysis eluted at a much more polar retention volume than nonoxidized phosphatidylcholine. Analysis of these polar lipids by fast atom bombardment mass spectrometry established that they were F2-isoprostane-containing species of phosphatidylcholine. Thus, unlike cyclooxygenase-derived prostanoids, F2 isoprostanes are initially formed in situ on phospholipids, from which they are subsequently released preformed, presumably by phospholipases. Molecular modeling of F2-isoprostane-containing phospholipids reveals them to be remarkably distorted molecules. Thus, the formation of these phospholipid species in lipid bilayers may contribute in an important way to alterations in fluidity and integrity of cellular membranes, well-known sequelae of oxidant injury. PMID- 1438269 TI - Role of fibrinogen alpha and gamma chain sites in platelet aggregation. AB - Fibrinogen (Fbg) mediates platelet aggregation by its interaction with the platelet glycoprotein IIb-IIIa (integrin alpha IIb beta 3). Peptides containing the amino acid sequence RGD derived from the alpha chain (residues alpha 95-97 and residues alpha 572-574) and the sequence HHLGGAKQAGDV derived from the carboxyl terminus of the gamma chain of Fbg (residues gamma 400-411) inhibit these interactions. To determine the role of these sequences in intact Fbg, recombinant human Fbg (rFbg), mutant rFbgs with an RGD-->RGE substitution at either position alpha 97 or alpha 574, and a rFbg gamma'-containing variant that has a carboxyl-terminal interruption in the HHLGGAKQAGDV sequence have been expressed in transfected BHK cells. Purified rFbg and the two RGE mutant Fbgs were similar to plasma Fbg in platelet aggregation assays. In contrast, the gamma' variant Fbg was markedly defective in platelet aggregation. These data support the proposals that the carboxyl-terminal region of the gamma chain of Fbg is essential for optimal platelet aggregation and that the alpha-chain RGD sequences are neither necessary nor sufficient for platelet aggregation. PMID- 1438270 TI - Phosphorylation/dephosphorylation of high-affinity IgE receptors: a mechanism for coupling/uncoupling a large signaling complex. AB - Engagement of high-affinity IgE receptors leads to activation of tyrosine and serine/threonine kinases and the immediate phosphorylation of receptor beta (serine and tyrosine) and gamma (threonine and tyrosine) chains. Receptor disengagement leads to dephosphorylation of beta and gamma chains via the action of undefined phosphatases. Here we have identified five distinct polypeptides associated with the high-affinity IgE-receptor tetrameric complex, which apparently become phosphorylated and dephosphorylated in sequence with the beta and gamma chains. Like beta chain, polypeptides pp180, pp48, pp42, and pp28 are phosphorylated on serine and tyrosine, whereas pp125 is only phosphorylated on serine. The phosphorylation of each of these receptor-associated polypeptides is antigen-dose dependent and is restricted to activated receptor complexes. Furthermore the physical association between pp125 and the receptor is quantitatively affected by receptor phosphorylation and dephosphorylation, indicating a coupling-uncoupling mechanism. Finally, in vitro kinase experiments show that activated receptor complexes are also physically associated with tyrosine and serine/threonine kinases as part of a larger complex containing the phosphorylated polypeptides. PMID- 1438271 TI - Diversity in the early tertiary anthropoidean radiation in Africa. AB - Between 1987 and 1991 recent field seasons in the Fayum Depression of Egypt have yielded five species and genera of primates that were earlier unknown. Three of these species and genera are described below. All these genera and species are known only from Fayum site L-41, which has been dated as of late Eocene age. In the Fayum, these 5 species from L-41 are added to 3 kinds of prosimians (1 species formally described) and 11 earlier named species of Anthropoidea. When certain undescribed species are added, the total of known Fayum primate species comes to 21, belonging to at least 10 genera, genera that, in turn, could belong to as many as seven families. This arguably represents more taxonomic diversity of primates, especially higher primates, than has been demonstrated before in one so spatially and temporally limited area. These facts argue that an important, perhaps primary, radiation of anthropoideans took place in the African Eocene. PMID- 1438272 TI - Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C. AB - Microvascular endothelial function in developing brain is particularly sensitive to lead toxicity, and it has been hypothesized that this results from the modulation of protein kinase C (PKC) by lead. We examined the effects of inorganic lead on an in vitro model of central nervous system endothelial differentiation in which astroglial cells induce central nervous system endothelial cells to form capillary-like structures. Capillary-like structure formation within C6 astroglial-endothelial cocultures was inhibited by lead acetate with 50% maximal inhibition at 0.5 microM total lead. Inhibition was independent of effects on cell viability or growth. Under conditions that inhibited capillary-like structure formation, we found that lead increased membrane-associated PKC in both C6 astroglial and endothelial cells. Prolonged exposure of C6 cells to 5 microM lead for up to 16 h resulted in a time-dependent increase in membranous PKC as determined by immunoblot analysis. Membranous PKC increased after 5-h exposures to as little as 50 nM lead and was maximal at approximately 1 microM. Phorbol esters were used to determine whether PKC modulation was causally related to the inhibition of endothelial differentiation by lead. Phorbol 12-myristate 13-acetate (10 nM) inhibited capillary-like structure formation by 65 +/- 5%, whereas 4 alpha-phorbol 12,13-didecanoate was without effect. These findings suggest that inorganic lead induces cerebral microvessel dysfunction by interfering with PKC modulation in microvascular endothelial or perivascular astroglial cells. PMID- 1438273 TI - The anticodon triplet is not sufficient to confer methionine acceptance to a transfer RNA. AB - Previous work suggested that the presence of the anticodon CAU alone was enough to confer methionine acceptance to a tRNA. Conversions of Escherichia coli nonmethionine tRNAs to a methionine-accepting species were obtained by substitutions reconstructing the whole methionine anticodon loop together with preservation (or introduction) of the acceptor stem base A73. We show here that the CAU triplet alone is unable to confer methionine acceptance when transplanted into a yeast aspartic tRNA. Both non-anticodon bases of the anticodon loop of yeast tRNA(Met) and A73 are required in addition to CAU for methionine acceptance. The importance of these non-anticodon bases in other CAU-containing tRNA frameworks was also established. These specific non-anticodon base interactions make a substantial thermodynamic contribution to the methionine acceptance of a transfer RNA. PMID- 1438274 TI - An intrastrand d(GpG) platinum crosslink in duplex M13 DNA is refractory to repair by human cell extracts. AB - We have examined the ability of human cell extracts to repair the most frequent DNA adduct caused by the cancer chemotherapeutic agent cis diamminedichloroplatinum(II). A circular DNA duplex with an intrastrand d(GpG) crosslink positioned at a specific site was synthesized. Human cell extracts were unable to induce repair synthesis in a 29-base-pair region encompassing the adduct or in adjacent regions. The same extracts could repair a single defined 2 acetylaminofluorene lesion in a similar location. When molecules containing the platinum adduct were cleaved by Escherichia coli UvrABC enzyme, human cell extracts could perform repair synthesis at the damaged site, suggesting that human enzymes fail to make incisions near the d(GpG) crosslink but can complete repair once incisions are made. This result indicates that most repair synthesis in DNA damaged with multiple cis-diamminedichloroplatinum(II) adducts takes place at lesions other than the predominant d(GpG) crosslink. These data support the idea that the clinical effectiveness of cis-diamminedichloroplatinum(II) may be explained by the inefficient repair of the major DNA adduct caused by this drug. PMID- 1438275 TI - Activity of the purified mutagenesis proteins UmuC, UmuD', and RecA in replicative bypass of an abasic DNA lesion by DNA polymerase III. AB - The introduction of a replication-inhibiting lesion into the DNA of Escherichia coli generates the induced, multigene SOS response. One component of the SOS response is a marked increase in mutation rate, dependent on RecA protein and the induced mutagenesis proteins UmuC and UmuD. A variety of previous indirect approaches have indicated that SOS mutagenesis results from replicative bypass of the DNA lesion by DNA polymerase III (pol III) holoenzyme in a reaction mediated by RecA, UmuC, and a processed form of UmuD termed UmuD'. To study the biochemistry of SOS mutagenesis, we have reconstituted replicative bypass with a defined in vitro system containing purified protein and a DNA substrate with a single abasic DNA lesion. The replicative bypass reaction requires pol III, UmuC, UmuD', and RecA. The nonprocessed UmuD protein does not replace UmuD' but inhibits the bypass activity of UmuD', perhaps by sequestering UmuD' in a heterodimer. Our experiments demonstrate directly that the UmuC-UmuD' complex and RecA act to rescue an otherwise stalled pol III holoenzyme at a replication blocking DNA lesion. PMID- 1438276 TI - Evolutionary conservation pattern of zinc-finger domains of Drosophila segmentation genes. AB - A number of genes of the developmental gene hierarchy in Drosophila encode transcription factors containing Cys2His2 zinc finger domains as DNA-binding motifs. To learn more about the evolution of these genes, it is necessary to clone the homologs, or more correctly the orthologs, from different species. Using PCR, we were able to obtain apparently orthologous fragments of hunchback (hb), Kruppel (Kr), and snail (sna) from a variety of arthropods and partly also from other animal phyla. Sequence alignments of these fragments show that the amino acid differences can normally not be correlated with the evolutionary distances of the respective species. This is due to an apparent saturation of potential replacements within the finger domains, which is also evident from the frequent occurrence of convergent replacements. Another recurrent feature of these alignments is that those amino acids that are directly involved in determining the DNA-binding specificity of the fingers are most conserved. Using in vitro bandshift experiments we can indeed show that the binding specificity of a hunchback finger fragment from different species is not changed. This implies that there is a high selective pressure to maintain the regulatory target elements of these genes during evolution. PMID- 1438277 TI - Identification and selective inhibition of an isozyme of steroid 5 alpha reductase in human scalp. AB - Steroid 5 alpha-reductase (EC 1.3.1.22) catalyzes the reduction of testosterone to dihydrotestosterone. The 5 alpha-reductase found in human scalp has been compared with the enzyme found in prostate. The scalp reductase has a broad pH optimum centered at pH 7.0. This is distinctly different from the pH optimum of 5.5 observed with the prostatic form of the enzyme. These enzymes also differ in the Km for testosterone, which is 25-fold higher for the scalp reductase. The most significant difference between the two enzymes is their affinity for inhibitors. Two 4-azasteroids and a 3-carboxyandrostadiene are potent inhibitors of the prostatic reductase but are weak inhibitors of the scalp reductase. In contrast, several N-4-methylazasteroids are good inhibitors of the scalp reductase. These findings support a proposal that different isozymes of 5 alpha reductase may exist in scalp and prostate. The scalp reductase was also compared to 5 alpha-reductase 1, one of the two enzymes recently cloned from human prostate [Andersson, S. & Russell, D. W. (1990) Proc. Natl. Acad. Sci. USA 87, 3640-3644; and Andersson, S., Berman, D. M., Jenkins, E. P. & Russell, D. W. (1991) Nature (London) 354, 159-161]. The characteristics of the cloned reductase 1 are comparable to those of the scalp reductase. PMID- 1438278 TI - The monoclonal CD4 antibody M-T413 inhibits cellular infection with human immunodeficiency virus after viral attachment to the cell membrane: an approach to postexposure prophylaxis. AB - Infectious cellular uptake of human immunodeficiency virus (HIV) is initiated by a complex sequence of interactions between the viral envelope gp120/gp41 complex and the cellular CD4 receptor resulting in the exposure of a hydrophobic region of gp41 that mediates the irreversible fusion of the virus with the cell membrane. Here we show that viral penetration into a susceptible cell can be inhibited by the high-affinity monoclonal CD4 antibody (CD4 mAb) M-T413 even when it is added as late as 30-120 min after the initial contact of virus with the cell membrane. Inhibition of infection was assessed by monitoring cultures for 34 days after exposure to virus using four different methods simultaneously, including detection of viral DNA by PCR. The interval during which HIV remains sensitive to postbinding neutralization by CD4 mAb depends on strain of virus and type of target cell. Preparations of recombinant soluble CD4 (and the immunoadhesin CD4-IgG1) were much less efficient when compared with mAb M-T413, particularly in blocking infection by fresh HIV-1 isolates. Also cellular transmission of HIV, as determined by syncytia formation within 24 hr, was prevented by mAb M-T413 when added within 45 min of contact of infected H9 cells with uninfected C8166 cells. Together with the favorable clinical experience obtained with CD4 mAbs as immunomodulatory drugs, these data suggest that infusion of CD4 mAb M-T413 may be a therapeutic modus for immediate prophylactic intervention after occupational exposure to HIV and for prevention of intrapartum mother-to-infant HIV transmission. PMID- 1438279 TI - Fatty acids regulate hepatic low density lipoprotein receptor activity through redistribution of intracellular cholesterol pools. AB - When the intake of dietary cholesterol in the hamster is constant, feeding the saturated 14:0 fatty acid (n-tetradecanoic acid) elevates the plasma low density lipoprotein (LDL) cholesterol concentration from 72 to 204 mg/dl, while the monounsaturated 18:1 fatty acid (cis-9-octadecenoic acid) lowers this level to 28 mg/dl. The 14:0 fatty acid lowers the hepatic cholesteryl ester concentration from 12 to 5 mg/g, while the abundance of this fatty acid in the ester fraction is increased 13-fold. Hepatic LDL receptor activity is depressed to 41% of control, while the LDL cholesterol production rate is increased to 132%. These changes account for the 3-fold increase in the plasma LDL cholesterol concentration. In contrast, feeding the 18:1 fatty acid increases hepatic cholesteryl ester concentration to 21 mg/g, and the abundance of this acid in the esters is increased 1.4-fold. Hepatic receptor activity is increased to 145%, while the production rate is suppressed to 68% of control. These changes account for the decrease in plasma LDL cholesterol level to 28 mg/dl. Despite these marked changes in LDL metabolism, however, the 14:0 and 18:1 fatty acids cause no change in net cholesterol balance across the liver. These results suggest that there are two fundamentally different mechanisms regulating hepatic LDL metabolism. One involves changes in net sterol balance across the liver brought about by alterations in the rate of cholesterol or bile acid absorption across the intestine, while the second is articulated through a redistribution of the putative sterol regulatory pool within the hepatocyte that is dictated by the type of long-chain fatty acid that reaches the liver. PMID- 1438280 TI - Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. AB - Ribozymes are RNAs that possess the dual properties of RNA sequence-specific recognition, analogous to conventional antisense molecules, and RNA substrate destruction via site-specific cleavage. The cleavage reaction is catalytic in that more than one substrate molecule is processed per ribozyme molecule. We have designed a hairpin ribozyme that cleaves human immunodeficiency virus type 1 (HIV 1) RNA in the leader sequence (at nucleotides +111/112 relative to the transcription initiation site). The ribozyme was tested in vitro and gave efficient and specific cleavage of RNA containing the leader sequence. To test the antiviral efficacy of this ribozyme, we have cotransfected into HeLa cells HIV-1 proviral DNA and a plasmid expressing the ribozyme from the human beta actin promoter. HIV-1 expression was inhibited as measured by p24 antigen levels and reduced Tat activity. The antiviral effect of the ribozyme appears to be specific and results from directed RNA cleavage; activity requires both a target sequence and a functional RNA catalytic center. These results suggest that this HIV-1-directed hairpin ribozyme may be useful as a therapeutic agent. PMID- 1438281 TI - Covalent modification of proteins by ligands of steroid hormone receptors. AB - Retinoylation, acylation with retinoic acid (RA), is a covalent modification of proteins occurring in a variety of eukaryotic cell lines. In this study, we found that proteins in HL-60 cells were labeled by 17 beta-[3H]estradiol (E2), [3H]progesterone (Pg), 1 alpha,25-dihydroxy[3H]vitamin D3 [1,25(OH)2D3], [125I]triiodothyronine (T3), [125I]thyroxine (T4), and [3H]prostaglandin E2 (PGE2). All of these hormones, except PGE2, are ligands of the steroid hormone receptor family. Addition to the growth medium of 5 microM ketoconazole, an inhibitor of cytochrome P450-dependent enzymes, increased about 2-fold the labeling of proteins by T3, T4, 1,25(OH)2D3, and PGE2. In contrast, ketoconazole did not change markedly the extent of labeling by RA, E2, or Pg. Alkaline methanolysis, which cleaves ester bonds, released variable percentages of the radioactive ligands bound to protein. These values were about 80% for RA and PGE2; 50% for T3, T4, and Pg; and 20% for E2 and 1,25(OH)2D3. Treatment with thioether-cleavage reagents, iodomethane or Raney nickel catalyst, released < 2% of the covalently bound ligands. Two-dimensional polyacrylamide gel electrophoresis patterns of labeled proteins were unique for each ligand. Proteins of M(r) 47,000 and 51,000 were labeled by RA, E2, T3, and T4. These proteins had the same mobilities as RI and RII, the cAMP-binding regulatory subunits of type I and type II cAMP-dependent protein kinases. 1,25(OH)2D3 also bound to proteins of M(r) 47,000 and 51,000. However, these proteins had pI values different from those of RI or RII. These results suggest that some activities of ligands of the steroid hormone receptor family and of PGE2 may be mediated by their covalent modification of proteins. PMID- 1438282 TI - High-level expression in Escherichia coli of enzymatically active fusion proteins containing the domains of mammalian cytochromes P450 and NADPH-P450 reductase flavoprotein. AB - This report describes the properties of two mammalian cytochromes P450 that have been expressed at high levels in Escherichia coli as enzymatically active fusion proteins containing the flavoprotein domain of rat NADPH-cytochrome P450 reductase (EC 1.6.2.4). Fusion proteins were prepared by engineering the cDNAs for the steroid-metabolizing bovine adrenal P450 17A with the cDNA for rat liver NADPH-P450 reductase with the introduction of a Ser-Thr linker to give a protein we have named rF450[mBov17A/mRatOR]L1. Similarly, the cDNA for the omega hydroxylase of rat liver (P450 4A1) was linked with the cDNA for rat liver NADPH P450 reductase to give rF450[mRat4A1/mRatOR]L1. A procedure involving disruption of transformed E. coli by sonication, isolation of membranes by differential centrifugation, solubilization with detergent, and affinity chromatography provided significant amounts of purified fusion proteins of approximately 118 kDa. The purified fusion proteins had turnover numbers for the metabolism of steroids (rF450[mBov17A/mRatOR]L1) or fatty acids (rF450[mRat4A1/mRatOR]L1) ranging from 10/min to 30/min in the absence of added phospholipid. Addition of purified rat liver cytochrome b5 stimulated the 17,20-lyase reaction for the conversion of 17-hydroxypregnenolone to dehydroepiandrosterone, and addition of purified rat NADPH-cytochrome P450 reductase enhanced the formation of omega--1 metabolites from lauric and arachidonic acids. NADPH oxidation was tightly coupled to substrate hydroxylation with the purified fusion proteins. PMID- 1438283 TI - Definition of the binding sites of individual zinc fingers in the transcription factor IIIA-5S RNA gene complex. AB - A series of polypeptides containing increasing numbers of zinc fingers of Xenopus transcription factor IIIA has been generated and binding to the 5S RNA gene internal control region has been studied in order to elucidate the mode of interaction of the individual fingers with DNA. By using a combination of DNase I footprinting, methylation interference, and differential binding to mixtures of DNA fragments differing in length by single base pairs, the binding sites for individual fingers have been defined. These results have led to a model for the interaction of transcription factor IIIA with the internal control region in which fingers 1-3 bind in the major groove of the promoter C block, fingers 7-9 bind in the major groove of the A block, and finger 5 binds in the major groove of the intermediate element. Fingers 4 and 6 each bind across the minor groove, spanning these promoter elements. PMID- 1438284 TI - Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis. AB - Torpedo acetylcholinesterase (AcChoEase, EC 3.1.1.7) and human butyrylcholinesterase (BtChoEase, EC 3.1.1.8), while clearly differing in substrate specificity and sensitivity to inhibitors, possess 53% sequence homology; this permitted modeling human BtChoEase on the basis of the three dimensional structure of Torpedo AcChoEase. The modeled BtChoEase structure closely resembled that of AcChoEase in overall features. However, six conserved aromatic residues that line the active-site gorge, which is a prominent feature of the AcChoEase structure, are absent in BtChoEase. Modeling showed that two such residues, Phe-288 and Phe-290, replaced by leucine and valine, respectively, in BtChoEase, may prevent entrance of butyrylcholine into the acyl-binding pocket. Their mutation to leucine and valine in AcChoEase, by site-directed mutagenesis, produced a double mutant that hydrolyzed butyrylthiocholine almost as well as acetylthiocholine. The mutated enzyme was also inhibited well by the bulky, BtChoEase-selective organophosphate inhibitor (tetraisopropylpyrophosphoramide, iso-OMPA). Trp-279, at the entrance of the active-site gorge in AcChoEase, is absent in BtChoEase. Modeling designated it as part of the "peripheral" anionic site, which is lacking in BtChoEase. The mutant W279A displayed strongly reduced inhibition by the peripheral site-specific ligand propidium relative to wild-type Torpedo AcChoEase, whereas inhibition by the catalytic-site inhibitor edrophonium was unaffected. PMID- 1438285 TI - Identification of endosialin, a cell surface glycoprotein of vascular endothelial cells in human cancer. AB - Cell surface antigens of transformed cells are the traditional targets for antibody-guided detection and therapy of solid neoplasms. Alternative targets may be found in the tumor stroma, which contains newly formed blood vessels, reactive fibroblasts, and extracellular matrix proteins. The F19 cell surface glycoprotein of reactive fibroblasts is a prototypic stromal antigen since it is found in the stroma of > 90% of common epithelial cancers but is absent or expressed at low levels in normal tissues and benign epithelial tumors. In the present study, we define an additional tumor stromal antigen, FB5, that is selectively expressed in vascular endothelial cells of malignant tumors. Immunohistochemical analysis of 128 tumors identified FB5 in endothelial cells in 67% of the samples (including 41 of 61 sarcomas, 26 of 37 carcinomas, and 18 of 25 neuroectodermal tumors) whereas normal blood vessels and other adult tissues tested lacked FB5 expression. In vitro studies showed that FB5 is a M(r) 165,000 cell surface glycoprotein, comprised of a M(r) 95,000 core polypeptide and highly sialyated O linked oligosaccharides but few if any N-linked sugars, and that the FB5 gene is located on chromosome 11q13-qter. The restricted tissue distribution of the FB5 protein, which we refer to as endosialin, suggests strategies for tumor imaging and therapy that are aimed primarily at the tumor vasculature. PMID- 1438286 TI - Arabidopsis alternative oxidase sustains Escherichia coli respiration. AB - Glutamyl-tRNA reductase, encoded by the hemA gene, is the first enzyme in porphyrin biosynthesis in many organisms. Hemes, important porphyrin derivatives, are essential components of redox enzymes, such as cytochromes. Thus a hemA Escherichia coli strain (SASX41B) is deficient in cytochrome-mediated aerobic respiration. Upon complementation of this strain with an Arabidopsis thaliana cDNA library, we isolated a clone which permitted the SASX41B strain to grow aerobically. The clone encodes the gene for Arabidopsis alternative oxidase, whose deduced amino acid sequence was found to have 71% identity with that of the enzyme from the voodoo lily, Sauromatum guttatum. The Arabidopsis protein is expressed as a 31-kDa protein in E. coli and confers on this organism cyanide resistant growth, which in turn is sensitive to salicylhydroxamate. This implies that a single polypeptide is sufficient for alternative oxidase activity. Based on these observations we propose that a cyanide-insensitive respiratory pathway operates in the transformed E. coli hemA strain. Introduction of this pathway now opens the way to genetic/molecular biological investigations of alternative oxidase and its cofactor. PMID- 1438287 TI - Nonreplicating vaccinia vector efficiently expresses recombinant genes. AB - Modified vaccinia Ankara (MVA), a highly attenuated vaccinia virus strain that has been safety tested in humans, was evaluated for use as an expression vector. MVA has multiple genomic deletions and is severely host cell restricted: it grows well in avian cells but is unable to multiply in human and most other mammalian cells tested. Nevertheless, we found that replication of viral DNA appeared normal and that both early and late viral proteins were synthesized in human cells. Proteolytic processing of viral structural proteins was inhibited, however, and only immature virus particles were detected by electron microscopy. We constructed an insertion plasmid with the Escherichia coli lacZ gene under the control of the vaccinia virus late promoter P11, flanked by sequences of MVA DNA, to allow homologous recombination at the site of a naturally occurring 3500-base pair deletion within the MVA genome. MVA recombinants were isolated and propagated in permissive avian cells and shown to express the enzyme beta galactosidase upon infection of nonpermissive human cells. The amount of enzyme made was similar to that produced by a recombinant of vaccinia virus strain Western Reserve, which also had the lacZ gene under control of the P11 promoter, but multiplied to high titers. Since recombinant gene expression is unimpaired in nonpermissive human cells, MVA may serve as a highly efficient and exceptionally safe vector. PMID- 1438288 TI - Assembly of a hetero-oligomeric membrane protein complex. AB - The maltose transporter of Escherichia coli is a hetero-oligomeric complex located in the cytoplasmic membrane of the cell. The in vivo assembly of this complex has been examined by using an assay based on the proteolytic sensitivity of one of its components, MalF. Immediately after synthesis and insertion into the membrane, MalF is sensitive to exogenously added proteases. In a time- and complex assembly-dependent fashion, MalF becomes protease resistant. Using this assay, we show that MalF is inserted into the membrane independently of other components of the transport complex. The assembly of the maltose transport complex occurs subsequently from a pool of freely diffusing protein in the membrane. This assembly process is efficient and occurs with rapid kinetics. PMID- 1438289 TI - Deposition of beta/A4 immunoreactivity and neuronal pathology in transgenic mice expressing the carboxyl-terminal fragment of the Alzheimer amyloid precursor in the brain. AB - The deposition of amyloid in senile plaques and along the walls of the cerebral vasculature is a characteristic feature of Alzheimer disease. The peptide comprising the carboxyl-terminal 100 amino acids of the beta-amyloid precursor protein (beta APP) has been shown to aggregate into amyloid-like fibrils in vitro and to be neurotoxic, suggesting that this fragment may play a role in the etiology of Alzheimer disease. To address this question, we expressed this carboxyl-terminal 100-amino acid peptide of beta APP in transgenic mice under the control of the brain dystrophin promoter. We used an antibody to the principal component of amyloid, beta/A4, to demonstrate cell-body and neuropil accumulation of beta/A4 immunoreactivity in the brains of 4- and 6-month-old transgenic mice. Only light cytoplasmic staining with this antibody was visible in control mice. In addition, immunocytochemical analysis of the brains with an antibody to the carboxyl terminus of beta APP revealed abnormal aggregation of this epitope of beta APP within vesicular structures in the cytoplasm and in abnormal-appearing neurites in the CA2/3 region of the hippocampus in transgenic mice, similar to its aggregation in the cells of Alzheimer disease brains. Thioflavin S histochemistry suggested accumulations of amyloid in the cerebrovasculature of transgenic mice with the highest expression of the beta APP-C100 transgene. These observations suggest that expression of abnormal carboxyl-terminal subfragments of beta APP in vivo may cause amyloidogenesis and specific neuropathology. PMID- 1438290 TI - Stopping the circadian pacemaker with inhibitors of protein synthesis. AB - The requirement for protein synthesis in the mechanism of a circadian pacemaker was investigated by using inhibitors of protein synthesis. Continuous treatment of the ocular circadian pacemaker of the mollusc Bulla gouldiana with anisomycin or cycloheximide substantially lengthened (up to 39 and 52 hr, respectively) the free-running period of the rhythm. To determine whether high concentrations of inhibitor could stop the pacemaker, long pulse treatments of various durations (up to 44 hr) were applied and the subsequent phase of the rhythm was assayed. The observed phases of the rhythm after the treatments were a function of the time of the end of the treatment pulse, but only for treatments which spanned subjective dawn. The results provide evidence that protein synthesis is required in a phase-dependent manner for motion of the circadian pacemaker to continue. PMID- 1438291 TI - Intact and amino-terminally shortened forms of insulin-like growth factor I induce mammary gland differentiation and development. AB - Growth hormone (GH) plays a role in regulating growth and differentiation of immature glandular structures in the mammary gland, but the mechanisms by which the hormone exerts these effects are unknown. We have previously found that GH stimulates insulin-like growth factor I (IGF-I) I mRNA production within the mammary glands of hypophysectomized rats. In this study we set out to determine if IGF-I administration could mimic the action of GH in initiating mammary gland differentiation and development. Two forms of IGF-I, intact and amino-terminally shortened [des-(1-3)-IGF-I], were found to induce the development of terminal end buds and the formation of alveolar structures in the mammary glands of hypophysectomized, castrated, and estradiol-treated sexually immature male rats. The effect of both forms of IGF-I was similar to that obtained with human GH, but the truncated form was at least 5 times more potent than intact IGF-I. These findings suggest that the inductive effect of GH on glandular differentiation is mediated by the GH-induced production of IGF-I or a related molecule within the mammary gland itself. PMID- 1438292 TI - Definition of a tumor suppressor locus within human chromosome 3p21-p22. AB - Cytogenetic abnormalities and high-frequency allele losses involving the short arm of human chromosome 3 have been identified in a variety of histologically different neoplasms. These findings suggest that a tumor-suppressor gene or genes may be located in the region of 3p14-p25, although there has been no definitive functional proof for the involvement of a particular region of 3p. We report a rapid genetic assay system that has allowed functional analysis of defined regions of 3p in the suppression of tumorigenicity in vivo. Interspecific microcell hybrids containing fragments of chromosome 3p were constructed and screened for tumorigenicity in athymic nude mice. Hybrid clones were obtained that showed a dramatic tumor suppression and contained a 2-megabase fragment of human chromosomal material encompassing the region 3p21 near the interface with 3p22. With these hybrid clones, we have defined a genetic locus at 3p21-p22 intimately involved in tumor suppression. PMID- 1438293 TI - Retinal rods and cones have distinct G protein beta and gamma subunits. AB - Guanine nucleotide-binding proteins (G proteins) involved in transmembrane signal transduction processes are heterotrimers composed of alpha, beta, and gamma subunits. The alpha subunit shows great diversity and is thought to confer functional specificity to a particular G protein. By contrast, the beta and gamma subunits appear much less diverse; in particular, the beta subunit is believed to have no role in G protein specificity. Using immunocytochemistry, we found distinct distribution patterns for different beta and gamma subunits in the retina. In particular, rod and cone photoreceptors, which both subserve phototransduction but differ in light-response properties, have different beta and gamma subunits in their outer segments. Thus, the G protein mediating phototransduction shows cell-specific forms of the beta and gamma subunits in addition to the alpha subunit. This surprising finding supports the hypothesis that these subunits may also contribute to functional specificity of a G protein. PMID- 1438294 TI - Cloning of a human galactokinase gene (GK2) on chromosome 15 by complementation in yeast. AB - A human cDNA encoding a galactokinase (EC 2.7.1.6) was isolated by complementation of a galactokinase-deficient (gal1-) strain of Saccharomyces cerevisiae. This cDNA encodes a predicted protein of 458 amino acids with 29% identity to galactokinase of Saccharomyces carlsbergensis. Previous studies have mapped a human galactokinase gene (GK1) to chromosome 17q23-25, closely linked to thymidine kinase. The galactokinase gene that we have isolated (GK2) is located on chromosome 15. The relationship between the disease locus for galactokinase deficiency galactosemia, which is responsible for cataracts in newborns and possibly presenile cataracts in adults, and the two galactokinase loci is unknown. PMID- 1438295 TI - The optimal number of major histocompatibility complex molecules in an individual. AB - A straightforward argument is presented to calculate the number of different major histocompatibility complex (MHC) molecules in an individual that maximizes the probability of mounting immune responses against a large number of foreign peptides. It is assumed that increasing the number of MHC molecules per individual, n, has three different effects: (i) it increases the number of foreign peptides that can be presented; (ii) it increases the number of different T-cell receptors (TCRs) positively selected in the thymus; but (iii) it reduces the number of TCRs by negative selection. The mathematical analysis shows that n = 1/f maximizes the number of different TCRs that pass through positive and negative selection and that n = 2/f maximizes the probability to mount immune responses against a large fraction of foreign peptides. Here f is the fraction of TCRs deleted by one MHC molecule. Both results depend on approximations that are discussed in the paper. The model presented has implications for our understanding of the evolutionary forces acting on the MHC. PMID- 1438296 TI - Association of efferent neurons to the compartmental architecture of the superior colliculus. AB - The superior colliculus is a layered structure in the mammalian midbrain serving multimodal sensorimotor integration. Its intermediate layers are characterized by a compartmental architecture. These compartments are apparent through the clustering of terminals of major collicular afferents, which in many instances match the heterogeneous distribution of tissue components such as acetylcholinesterase, choline acetyltransferase, substance P, and parvalbumin. The present study was undertaken to determine whether efferent cells observe this compartmental architecture. It was found that subpopulations of both descending and ascending collicular efferents originate from perikarya situated in characteristic positions relative to the collicular compartments defined by elevated acetylcholinesterase activity and that their dendrites appear to be specifically coordinated with the heterogeneous environment. With the specific interlocking of afferent and efferent neurons through spatially distinguished neural networks, the compartmental architecture apparently constitutes an essential element for the determination of information flow in the superior colliculus. PMID- 1438297 TI - Amino acid substitution matrices from protein blocks. AB - Methods for alignment of protein sequences typically measure similarity by using a substitution matrix with scores for all possible exchanges of one amino acid with another. The most widely used matrices are based on the Dayhoff model of evolutionary rates. Using a different approach, we have derived substitution matrices from about 2000 blocks of aligned sequence segments characterizing more than 500 groups of related proteins. This led to marked improvements in alignments and in searches using queries from each of the groups. PMID- 1438298 TI - Molecular cloning and primary structure of the human blood group RhD polypeptide. AB - The RH (rhesus) blood group locus from RhD-positive donors is composed of two homologous structural genes, one of which encodes the Cc and Ee polypeptides, whereas the other, which is missing in the RhD-negative condition, encodes the D protein that carries the major antigen of the RH system. Recently, different splicing isoforms transcribed from the CcEe gene were isolated. We report now the characterization of two other Rh clones, RhII and RhXIII, generated by alternative choices for poly(A) addition sites that were identified as the RhD gene transcripts. That these cDNAs represented the RhD messenger and that the previously described Rh clones were derived from the CcEe gene was demonstrated by amplification of RhII/XIII sequences only from D-positive genomes and by cloning and sequencing of D- and CcEe-specific gene fragments. The predicted translation product of the RhD mRNA is a 417-amino acid protein (M(r) = 45,500) that exhibited a similar membrane organization with 13 bilayer-spanning domains compared with the polypeptide encoded by the CcEe gene. The D and Cc/Ee polypeptides differ by 36 amino acid substitutions (8.4% divergence), but the NH2 and COOH-terminal regions of the two proteins are well conserved. Similarly, five of the six cysteine residues of the Cc/Ee proteins were conserved in the D protein, including the unique exofacial cysteine, which is critical for antigenic reactivity. The sequence homology between the Cc/Ee and D proteins supports the concept that the genes encoding these polypeptides have evolved by duplication of a common ancestor gene. PMID- 1438299 TI - Induction of aP2 gene expression by nonmetabolized long-chain fatty acids. AB - Long-chain fatty acids (FA) have been shown to regulate expression of the gene for the adipocyte FA-binding protein aP2. We examined whether this effect was exerted by FA themselves or by a FA metabolite. The alpha-bromo derivative of palmitate, an inhibitor of FA oxidation, was synthesized in the radioactive form, and its metabolism was investigated and correlated with its ability to induce aP2 in Ob1771 preadipocytes. alpha-Bromopalmitate was not utilized by preadipocytes. It was not cleared from the medium over a 24-hr period and was not incorporated into cellular lipids. Short incubations indicated that alpha-bromopalmitate exchanged across the preadipocyte membrane but remained in the free form inside the cell. In line with this, preadipocyte homogenates did not activate alpha bromopalmitate to the acyl form. However, although it was not metabolized, bromopalmitate was much more potent than native FA in inducing aP2 gene expression. Induction exhibited the characteristics previously described for native FA, indicating that a similar if not identical mechanism was involved. The data indicated that induction of aP2 was exerted by unprocessed FA. Finally, in contrast to preadipocytes, adipocytes metabolized bromopalmitate. This reflected increased activity with cell differentiation of a palmitoyl-CoA synthase that could activate palmitate and bromopalmitate at about one-fifth the rate for palmitate. In preadipocytes, the predominant fatty-acyl-CoA synthase, arachidonyl CoA synthase, had very low affinity for both FA. Increased activity of the palmitoyl-CoA synthase, which has a wider substrate range, is likely to be important for initiation of lipid deposition. PMID- 1438300 TI - Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid. AB - By comparing the amino acid sequences of 11 mammalian and 1 avian prion proteins (PrP), structural analyses predicted four alpha-helical regions. Peptides corresponding to these regions of Syrian hamster PrP were synthesized, and, contrary to predictions, three of the four spontaneously formed amyloids as shown by electron microscopy and Congo red staining. By IR spectroscopy, these amyloid peptides exhibited secondary structures composed largely of beta-sheets. The first of the predicted helices is the 14-amino acid peptide corresponding to residues 109-122; this peptide and the overlapping 15-residue sequence 113-127 both form amyloid. The most highly amyloidogenic peptide is AGAAAAGA, which corresponds to Syrian hamster PrP residues 113-120 and is conserved across all species for which the PrP sequence has been determined. Two other predicted alpha helices corresponding to residues 178-191 and 202-218 form amyloids and exhibit considerable beta-sheet structure when synthesized as peptides. These findings suggest the possibility that the conversion of the cellular isoform of PrP to the scrapie isoform of PrP involves the transition of one or more putative PrP alpha helices into beta-sheets and that prion diseases are disorders of protein conformation. PMID- 1438301 TI - Frog secretions and hunting magic in the upper Amazon: identification of a peptide that interacts with an adenosine receptor. AB - A frog used for "hunting magic" by several groups of Panoan-speaking Indians in the borderline between Brazil and Peru is identified as Phyllomedusa bicolor. This frog's skin secretion, which the Indians introduce into the body through fresh burns, is rich in peptides. These include vasoactive peptides, opioid peptides, and a peptide that we have named adenoregulin, with the sequence GLWSKIKEVGKEAAKAAAKAAGKAALGAVSEAV as determined from mass spectrometry and Edman degradation. The natural peptide may contain a D amino acid residue, since it is not identical in chromatographic properties to the synthetic peptide. Adenoregulin enhances binding of agonists to A1 adenosine receptors; it is accompanied in the skin secretion by peptides that inhibit binding. The vasoactive peptide sauvagine, the opioid peptides, and adenoregulin and related peptides affect behavior in mice and presumably contribute to the behavioral sequelae observed in humans. PMID- 1438302 TI - A conserved double-stranded RNA-binding domain. AB - We have identified a double-stranded (ds)RNA-binding domain in each of two proteins: the product of the Drosophila gene staufen, which is required for the localization of maternal mRNAs, and a protein of unknown function, Xlrbpa, from Xenopus. The amino acid sequences of the binding domains are similar to each other and to additional domains in each protein. Database searches identified similar domains in several other proteins known or thought to bind dsRNA, including human dsRNA-activated inhibitor (DAI), human trans-activating region (TAR)-binding protein, and Escherichia coli RNase III. By analyzing in detail one domain in staufen and one in Xlrbpa, we delimited the minimal region that binds dsRNA. On the basis of the binding studies and computer analysis, we have derived a consensus sequence that defines a 65- to 68-amino acid dsRNA-binding domain. PMID- 1438303 TI - An Arabidopsis serine/threonine kinase homologue with an epidermal growth factor repeat selected in yeast for its specificity for a thylakoid membrane protein. AB - A number of molecules have recently been described that effect the correct transport and assembly of cytoplasmically synthesized proteins to cellular membranes. To identify proteins that bind or modify other proteins during the process of membrane translocation, we developed a yeast selection scheme that employs the yeast transcriptional activator GAL4. This selection facilitates the isolation of cDNAs that encode proteases and binding proteins for known target peptide sequences. We report the isolation of an Arabidopsis cDNA encoding a polypeptide that can interact with the amino terminus of a ligh-harvesting chlorophyll a/b-binding protein (LHCP), a cytoplasmically synthesized protein that is integral to the chloroplast thylakoid membrane. The cDNA was selected in yeast from an Arabidopsis expression library for its ability to inhibit a transcriptional activator GAL4-LHCP fusion protein, but not inhibit native GAL4 protein. The LHCP amino-terminal sequences included in the fusion protein are known to regulate LHCP biogenesis and function. The Arabidopsis cDNA encodes a 595-amino acid protein with at least two functional domains, one with similarity to the family of protein-serine/threonine kinases and another that contains an epidermal growth factor repeat. The identification of an EGF repeat in Arabidopsis indicates that the motif is conserved between the plant and animal kingdoms. Hybridization studies indicate that this gene is likely to be present in other genera of plants. Its mRNA is detected in green leaves but not in other plant tissues or in etiolated plants. The specificity in yeast and the expression pattern in plants together are suggestive of a role for this protein kinase in the assembly or regulation of LHCP. PMID- 1438304 TI - Expression cloning of a reserpine-sensitive vesicular monoamine transporter. AB - A cDNA for a rat vesicular monoamine transporter, designated MAT, was isolated by expression cloning in a mammalian cell line (CV-1). The cDNA sequence predicts a protein of 515 amino acids with 12 putative membrane-spanning domains. The characteristics of [3H]serotonin accumulation by CV-1 cells expressing the cDNA clone suggested sequestration by an intracellular compartment. In cells permeabilized with digitonin, uptake was ATP dependent with an apparent Km of 1.3 microM. Uptake was abolished by the proton-translocating ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone and with tri-(n-butyl)tin, an inhibitor of the vacuolar H(+)-ATPase. The rank order of potency to inhibit uptake was reserpine > tetrabenazine > serotonin > dopamine > norepinephrine > epinephrine. Direct comparison of [3H]monoamine uptake indicated that serotonin was the preferred substrate. Photolabeling of membranes prepared from CV-1 cells expressing MAT with 7-azido-8-[125I]iodoketanserin revealed a predominant tetrabenazine-sensitive photolabeled glycoprotein with an apparent molecular mass of approximately 75 kDa. The mRNA that encodes MAT was present specifically in monoamine-containing cells of the locus coeruleus, substantia nigra, and raphe nucleus of rat brain, each of which expresses a unique plasma membrane reuptake transporter. The MAT cDNA clone defines a vesicular monoamine transporter representing a distinct class of neurotransmitter transport molecules. PMID- 1438305 TI - Functional inhibition of hematopoietic and neurotrophic cytokines by blocking the interleukin 6 signal transducer gp130. AB - Functional pleiotropy and redundancy are characteristic features of cytokines. To understand the signaling mechanisms of such cytokines, we have proposed a two chain interleukin (IL) 6 receptor model: IL-6 triggers the association of a ligand-binding chain (IL-6 receptor) and a nonbinding signal transducer (gp130) to form a high-affinity receptor complex, resulting in transmission of the signal by the cytoplasmic portion of gp130. This model would explain the functional redundancy of cytokines if we were to assume that gp130 interacts with several different receptor chains. Here we present data indicating that gp130 functions as a common signal transducer for IL-6, oncostatin M, leukemia inhibitory factor, and ciliary neurotrophic factor. We show that anti-gp130 monoclonal antibodies completely block the biological responses induced by all of these factors. Since leukemia inhibitory factor functions as a cholinergic differentiation factor in nerve cells, as does ciliary neurotrophic factor, these results suggest that gp130 may also play a role in the nervous system. PMID- 1438306 TI - Regulation of N-region diversity in antigen receptors through thymocyte differentiation and thymus ontogeny. AB - The random addition of "N nucleotides" by terminal deoxynucleotidyltransferase (TdT) is an important component of the diversity of T-cell receptor genes. We have investigated the expression of TdT during thymocyte differentiation and thymus ontogeny. TdT gene transcripts are confined to immature thymocytes of the cortex, being down-regulated concomitantly with recombination-activating gene transcripts after positive selection of mature medullary T cells. According to in situ hybridization, TdT RNA is absent from the neonatal thymus, but it appears 3 to 5 days after birth, just before the appearance of significant N-region diversity in T-cell receptor junctional sequences but clearly after the thymus attains competence at clonal deletion. PMID- 1438307 TI - XY sex reversal associated with a deletion 5' to the SRY "HMG box" in the testis determining region. AB - The human testis-determining factor resides within a 35-kilobase (kb) region of the Y chromosome immediately adjacent to the pseudoautosomal boundary. A candidate gene for human sex determination (SRY) was isolated in this region. Here, we describe a study of 25 cases of XY females with pure gonadal dysgenesis for mutations on the Y chromosome short arm, including SRY. Southern blotting revealed a sex-reversed female harboring a deletion extending from approximately 8 kb from the pseudoautosomal boundary of the Y chromosome to at least 33 kb and no more than 60 kb upstream, toward the centromere. The deletion begins no more than 1.8 kb upstream from the first ATG of the SRY open reading frame present in the clone pY53.3. To our knowledge, no mutation has been described previously outside the SRY "HMG box" on the short arm of the Y chromosome, which is associated with sex reversal. Since the 5' extent of the SRY transcriptional unit has not been defined, the deletion may remove upstream exons of SRY and/or transcriptional regulatory motifs, either situation resulting in lack of testicular development. It cannot be formally excluded that the mutation removes a second locus, independent of SRY, that is critical for sex determination. Denaturant gradient gel electrophoresis analysis of the SRY open reading frame in the remaining 24 cases revealed de novo single base-pair transitions in the SRY conserved domain in 4 cases. PMID- 1438308 TI - Cornifin, a cross-linked envelope precursor in keratinocytes that is down regulated by retinoids. AB - In this study, we have characterized the cDNA clone SQ37 that was isolated previously from a rabbit squamous cell library. The gene encodes a 14-kDa protein that appears to function as a component of the cross-linked envelope in squamous differentiating cells. The protein, which has been named cornifin, has a high content of proline (31%), glutamine (20%), and cysteine (11%) and contains 13 repeats of an octapeptide (consensus sequence, EPCQPKVP) at its C terminus. SQ37 mRNA and protein are induced during squamous differentiation of rabbit tracheal (RbTE) cells and human epidermal keratinocytes. This induction is repressed by retinoids. Immunohistochemical studies reveal SQ37 immunoreactivity in fragmented cross-linked envelopes from squamous-differentiated RbTE cells and in the suprabasal layers of the epidermis. In situ hybridization analysis showed that the presence of SQ37 mRNA is restricted to the suprabasal layers. Treatment of RbTE cells with a Ca2+ ionophore induces cross-linking of the SQ37 protein into higher molecular weight complexes. This cross-linking reaction appears to be mediated by transglutaminase type I. Our observations suggest that the protein encoded by SQ37 participates in the assembly of the cross-linked envelope. PMID- 1438309 TI - Excision repair at individual bases of the Escherichia coli lacI gene: relation to mutation hot spots and transcription coupling activity. AB - To determine whether base-to-base variations in the rate of excision repair influence the distribution of mutations, we have developed a method to measure UV photoproducts at individual nucleotides in the Escherichia coli chromosome. Specific gene fragments are 3' end-labeled using a sequence-specific oligonucleotide to direct the site of labeling, and photoproducts are identified by enzymatic incision. On the nontranscribed strand of the E. coli lacI gene, the cyclobutane pyrimidine dimer frequency was 2- to 8-fold higher in chromosomal DNA than in a cloned DNA fragment. The chromosomal lesion frequency corresponded to the frequency of UV-induced mutations at mutation hot spots reported in the literature. Only 0-30% of cyclobutane dimers at various sites on this strand were excised in 20 min. In contrast, repair on the transcribed strand was 80-90% complete in 20 min. However, the transcribed strand contained an excision repair "slow spot" at the site of its single mutation hot spot: At this site, no repair occurred for the first 10 min, after which repair proceeded more slowly than typical of that strand. In an mfd strain, deficient in a factor that couples repair to transcription in cell extracts, the excision rate at individual nucleotides on the transcribed strand was minimal at most sites for at least 30 min. Wild-type E. coli's bias for producing mutations at photoproducts on the nontranscribed strand, reported to require the mfd gene, therefore appears to be due to an excision repair system specific for the transcribed strand of chromosomal DNA. PMID- 1438310 TI - Transcription-repair coupling determines the strandedness of ultraviolet mutagenesis in Escherichia coli. AB - We have analyzed the spectra of UV-induced mutations in the lacI gene of a wild type and an mfd strain of Escherichia coli. mfd strains have been recently proposed to be deficient in a factor coupling DNA repair and transcription. Analysis of UV-induced mutations occurring at adjacent pyrimidines showed that mutations in the wild-type strain arose largely from the nontranscribed strand but arose predominantly from the transcribed strand in the mfd strain. The overall strand switch was 14-fold. One mutation, G.C-->A.T in the lacI initiation codon, showed a > 300-fold shift. No effect was observed for mutations at non pyrimidine-pyrimidine sequences. These results provide in vivo evidence for a key role of the mfd gene in controlling the strandedness of mutagenesis and support the proposed role of the mfd gene product in directing DNA excision repair to the transcribed strand of a damaged gene. PMID- 1438311 TI - Adoptive transfer of skin-selective autoimmunity induced by Skn alloantigenic disparities. AB - Two unlinked genes of the mouse, Skn-1 and Skn-2, each with alterative alleles, specify alternative cell-surface Skn alloantigens expressed only by epidermal and neural cells. C57BL/6 (B6) and A/J (A) strain mice differ at both Skn loci. Thus lethally irradiated B6 mice restored with (B6 x A)F1 hybrid hematopoietic cells [(B6 x A)/B6 chimeras] reject A strain (Skn-incompatible) skin grafts. Our studies were designed primarily to test the inference that (B6 x A)F1 lymphoid cells, after differentiating in B6 recipients, which lack the Skn alloantigens of A strain mice, may make an Skn-related, skin-selective autoimmune response when returned to their native (B6 x A)F1 habitat. Severe cutaneous lesions did, indeed, ensue after spleen cells of (B6 x A)/B6 chimeras were transferred to (B6 x A)F1 recipients, provided that three conditions were met--namely, (i) priming of the (B6 x A)/B6 chimeric donor by grafting and rejection of Skn-incompatible A strain skin grafts, (ii) stimulation of the recipient's skin as from shaving, at which sites the lesions were mainly located, and (iii) pretreatment of the (B6 x A)F1 recipients with cyclophosphamide or sublethal irradiation. Spleen cells of control female chimeras primed by grafting and rejection of H-Y (Skn-compatible) B6 male skin failed to incite the Skn-typical cutaneous lesions in (B6 x A)F1 recipients, indicating that these lesions were Skn-specific and not a nonspecific consequence of incompatible skin grafting per se. Normally compatible A strain skin grafts, but not Skn-compatible B6 skin grafts, were rejected by cyclophosphamide-treated (B6 x A)F1 recipients of (B6 x A)/B6 spleen cells from Skn-primed chimera donors. Treatment of primed chimeras' spleen cells with antiserum to H-2a (A strain) specifically abolished their capacity to adoptively incite the Skn-related autoimmune syndrome, confirming that the immune cells responsible are of (B6 x A)F1 origin and are not residual B6 derivatives. These findings add weight to the status of Skn systems as agents of tissue-selective histoincompatibility and, perhaps, of clinical disorders with a known or suspected autoimmune basis affecting the skin. PMID- 1438312 TI - The 1-aminocyclopropane-1-carboxylate synthase gene family of Arabidopsis thaliana. AB - Genomic sequences encoding five divergent 1-aminocyclopropane-1-carboxylic acid (ACC) synthase polypeptides (ACC1, ACC2, ACC3, ACC4, and ACC5) have been isolated from Arabidopsis thaliana by using heterologous cDNAs and PCR fragments amplified from genomic DNA with degenerate oligonucleotide primers. Each gene is located on a different chromosome in the Arabidopsis genome. The genes are differentially expressed during development and in response to environmental stimuli. Protein synthesis inhibition derepresses the expression of all genes but most dramatically derepresses that of ACC2, suggesting that their expression may be under negative control. The sequence of ACC2 was determined, and its transcription initiation site was defined. Authenticity of the polypeptide encoded by the gene was confirmed by expression experiments in Escherichia coli. The predicted size of the protein is 55,623 Da, and it contains the 11 invariant amino acid residues conserved between aminotransferases and ACC synthases from various plant species. Comparative analysis of structural and expression characteristics of ACC synthase genes from Arabidopsis and other plant species suggests that the sequence divergence of the ACC synthase genes and possibly the distinct regulatory networks governing the expression of ACC synthase subfamilies arose early in plant evolution and before the divergence of monocots and dicots. PMID- 1438313 TI - Stimulatory and inhibitory regulation of calcium-activated potassium channels by guanine nucleotide-binding proteins. AB - The regulation of membrane ion channels by guanine nucleotide-binding proteins (G proteins) has been described in numerous tissues. This regulation has been shown to involve the membrane-delimited stimulatory action of G proteins on ion channels. We now show that single calcium-activated potassium channels (KCa channels) in airway smooth muscle cells are both stimulated and inhibited by G proteins in membrane patches. We demonstrate that the beta-adrenergic agonist isoproterenol stimulates channel activity via the alpha subunit of the stimulatory G protein of adenylyl cyclase, Gs, and that channel opening is inhibited by the action of the muscarinic agonist methacholine, acting via a pertussis toxin-sensitive G protein. Isoproterenol stimulated and methacholine inhibited channel activity in the same outside-out patches when GTP was present at the cytosolic surface of the patch. In inside-out patches, addition of GTP and guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]) augmented channel activity when isoproterenol was included in the patch pipette, and inhibited channel activity when methacholine was included in the pipette. Consistent with these results, in the presence of GTP[gamma S], the alpha subunit of Gs (alpha s.GTP[gamma S] complex) opened KCa channels in a dose-dependent manner, whereas in the presence of guanosine 5'-[beta-thio]diphosphate, alpha s had no effect. By contrast, application of activated alpha i or alpha o proteins did not inhibit channel activity in inside-out patches, indicating that channel inhibition is more complex than a simple alpha subunit/channel interaction, similar to the complex inhibitory regulation of adenylyl cyclase. These results suggest that hormonal regulation of KCa channels shares substantial features with the regulation of adenylyl cyclase and demonstrate that a single ion channel may serve as the regulatory target for the membrane-delimited action of stimulatory and inhibitory G proteins. Moreover, they demonstrate a potentially important functional pathway by which beta-adrenergic and other Gs-linked receptors stimulate relaxation of smooth muscle, independent of cAMP-dependent protein phosphorylation. PMID- 1438314 TI - Antithrombotic effect of beta,beta'-monochloromethylene diadenosine 5',5"'-P1,P4 tetraphosphate. AB - The feasibility of using beta,beta'-monochloromethylene diadenosine 5',5"'-P1,P4 tetraphosphate (AppCHCl-ppA) as an antithrombotic agent was studied in a rabbit intracarotid cannula thrombosis model previously shown to be sensitive to antiplatelet agents. This analogue, having a P-C-P bridge in place of a P-O-P internucleoside linkage, has been found resistant to phosphodiesterase activity. Rabbits were infused with the dinucleotide at a dose of 50 mg per kg over a 2-hr period, at a controlled rate by pump. A 1-cm length of polyethylene cannula (1 mm i.d.) was tied into the carotid artery. Animals were stable under general anesthesia during the entire period of the experiment. In the control group, 16 of 20 animals formed clots, an incidence of 80%, whereas in the test animals, 6 of the 20 formed clots (30% incidence, P < 0.05). After preincubation of whole blood with 50 microM AppCHClppA at 37 degrees C for up to 3 hr, a consistent suppression of ADP-induced platelet aggregation was observed. The present study suggests that AppCHClppA may be useful as an antithrombotic agent in certain clinical situations, such as hemodialysis, arteriovenous shunts, and introduction of artificial heart valves. It may also possibly prevent extension of recent clots. The toxicity and metabolism of AppCHClppA have, however, yet to be explored. PMID- 1438316 TI - Uranium-loaded apoferritin with antibodies attached: molecular design for uranium neutron-capture therapy. AB - A method is described to deliver 235U to tumors; the isotope would then be fissioned by incident neutrons, producing localized lethal radiation sufficient for therapy. Apoferritin was loaded with an average of approximately 800 238U atoms per molecule. Stability of the loaded apoferritin in solution was improved, so that only 8% loss of uranium occurred after 8 days at pH 7. Fab' antibody fragments were covalently attached to the uranium-loaded apoferritin, and the immunoreactivity of the conjugate was 92% of that for antibody alone. Such bio uranium constructions should provide significant advantages over boronated antibodies to meet the requirements for clinical neutron-capture therapy. PMID- 1438315 TI - Preferential elevation of protein kinase C isoform beta II and diacylglycerol levels in the aorta and heart of diabetic rats: differential reversibility to glycemic control by islet cell transplantation. AB - In the present study, we have measured protein kinase C (PKC) specific activities and total diacylglycerol (DAG) level in the aorta and heart of rats, which showed that after 2 weeks of streptozotocin (STZ)-induced diabetes, membranous PKC specific activity and total DAG content were increased significantly by 88% and 40% in the aorta and by 21% and 72% in the heart, respectively. Hyperglycemia was identified as being a causal factor since elevated glucose levels increased DAG levels in cultured aortic endothelial and smooth muscle cells. Analysis by immunoblotting revealed that only alpha and beta II PKC isoenzymes are detected in these two tissues and vascular cells among those studied. In STZ-induced diabetic rats, beta II isoenzyme is preferentially increased in both aorta and heart, whereas PKC alpha did not change significantly. The increases in membranous PKC specific activity and DAG level are observed in both spontaneous diabetes-prone diabetic BB rats as well as in STZ-induced diabetic BB and Sprague Dawley rats, which persisted for up to 5 weeks. After 2 weeks of diabetes without treatment, the normalization of blood glucose levels for up to 3 weeks with islet cell transplants in STZ-induced diabetic BB rats reversed the biochemical changes only in the heart, but not in the aorta. These results suggest that PKC activity and DAG level may be persistently activated in the macrovascular tissues from diabetic animals and indicate a possible role for these biochemical parameters in the development of diabetic chronic vascular complications. PMID- 1438317 TI - Dynamic mapping of the human visual cortex by high-speed magnetic resonance imaging. AB - We report the use of high-speed magnetic resonance imaging to follow the changes in image intensity in the human visual cortex during stimulation by a flashing checkerboard stimulus. Measurements were made in a 2.1-T, 1-m-diameter magnet, part of a Bruker Biospec spectrometer that we had programmed to do echo-planar imaging. A 15-cm-diameter surface coil was used to transmit and receive signals. Images were acquired during periods of stimulation from 2 s to 180 s. Images were acquired in 65.5 ms in a 10-mm slice with in-plane voxel size of 6 x 3 mm. Repetition time (TR) was generally 2 s, although for the long flashing periods, TR = 8 s was used. Voxels were located onto an inversion recovery image taken with 2 x 2 mm in-plane resolution. Image intensity increased after onset of the stimulus. The mean change in signal relative to the prestimulation level (delta S/S) was 9.7% (SD = 2.8%, n = 20) with an echo time of 70 ms. Irrespective of the period of stimulation, the increase in magnetic resonance signal intensity was delayed relative to the stimulus. The mean delay measured from the start of stimulation for each protocol was as follows: 2-s stimulation, delay = 3.5 s (SD = 0.5 s, n = 10) (the delay exceeds stimulus duration); 20- to 24-s stimulation, delay = 5 s (SD = 2 s, n = 20). PMID- 1438319 TI - Gene family for an elicitor-induced sesquiterpene cyclase in tobacco. AB - The initial step in the conversion of the isoprenoid intermediate farnesyl diphosphate to the sesquiterpenoid phytoalexin capsidiol in elicitor-treated tobacco tissues is catalyzed by an inducible sesquiterpene cyclase [5-epi aristolochene synthase (EAS)]. Two independent cDNA clones (cEAS1 and cEAS2) encoding EAS were isolated from an elicitor-induced tobacco cDNA library by differential hybridization and subsequently were characterized by hybrid selection--in vitro translation. Insertion of cEAS1, a partial cDNA clone encoding 175 C-terminal amino acids, into an Escherichia coli expression vector resulted in accumulation of a fusion protein immunodetectable with EAS-specific polyclonal antibodies. The cDNA clones were used to isolate two full-length EAS genes that mapped 5 kilobases (kb) apart on one 15-kb genomic clone. The nucleotide sequences of the structural gene components were identical from 388 base pairs (bp) upstream of the transcription initiation site to 40 bp downstream of the translation termination codon, suggesting a relatively recent duplication event. The genes consist of 1479-bp open reading frames, each containing five introns and specifying 56,828-Da proteins. The N-terminal amino acid sequence deduced from the genomic clones was identical to the first 16 amino acids of the EAS protein identifiable by Edman degradation. RNA blot hybridization with cEAS1 demonstrated a mRNA induction time course consistent with the induction of the EAS mRNA translational activity with maximum levels 4-6 h after elicitation. EAS mRNA was not detected in control cells. DNA blot-hybridization analysis of genomic DNA revealed a copy number of approximately 12-15 for EAS-like genes in the tetraploid tobacco genome. The conservation of a putative allelic prenyl diphosphate binding motif is also discussed. PMID- 1438318 TI - Possible mechanism by which stress accelerates growth of virally derived tumors. AB - Stress accelerates the growth of certain types of tumors. Here we report a possible metabolic mechanism underlying this phenomenon. Some early features of transformation include increased number of glucose transporters and greatly enhanced rates of glucose uptake; this adaptation accommodates the vast energy demands needed for neoplastic growth. In contrast, glucocorticoids, a class of steroid hormones secreted during stress, inhibit glucose transport in various tissues; this is one route by which circulating glucose concentrations are raised during stress. We reasoned that should transformed cells become resistant to this inhibitory action of glucocorticoids, such cells would gain preferential access to these elevated concentrations of glucose. In agreement with this, we observed that Fujinami sarcoma virus-transformed fibroblasts became resistant to this glucocorticoid action both in vitro and in the rat. As a result, under conditions where glucocorticoids exerted catabolic effects upon nontransformed fibroblasts (inhibition of metabolism and ATP concentrations), the opposite occurred in the virally transformed cells. We observe that this glucocorticoid resistance upon transformation cannot be explained by depletion of glucocorticoid receptors; previous studies have suggested that transformation causes an alteration in trafficking of such receptors. Because of this resistance of transformed fibroblasts to the inhibitory effects of glucocorticoids upon glucose transport, glucose stores throughout the body are, in effect, preferentially shunted to such tumors during stress. PMID- 1438320 TI - Saving the "library of life". AB - A broad program of freezing species in threatened ecospheres could preserve biodiversity for eventual use by future generations. Sampling without studying can lower costs dramatically. Local labor can do most of the gathering. Plausible costs of collecting and cryogenically suspending the tropical rain forest species, at a sampling fraction of 10(-6), are about 2 billion dollars for a full century. Much more information than species DNA will be saved, allowing future biotechnology to derive high information content and perhaps even resurrect then extinct species. Parallel programs of in situ and other ex situ preservation are essential to allow later expression of frozen genomes in members of the same genus. This is a broad proposal that should be debated throughout the entire scientific community. PMID- 1438321 TI - The effect of nutrition of the fetus and neonate on cardiovascular disease in adult life. PMID- 1438322 TI - Food and biological clocks. PMID- 1438323 TI - Breast and gut: the relationship between lactating mammary function and neonatal gastrointestinal function. PMID- 1438324 TI - Maternal and environmental influences on thermoregulation in the neonate. PMID- 1438326 TI - Tocopherol transport and absorption. PMID- 1438325 TI - Diet effects on enterocyte development. PMID- 1438327 TI - The transport of vitamin C and effects of disease. PMID- 1438329 TI - Dose dependence of zinc and manganese absorption in man. PMID- 1438328 TI - The transport of iron and copper across the cell membrane: different mechanisms for different metals? PMID- 1438330 TI - Folate-vitamin B12 interrelationships in the central nervous system. PMID- 1438331 TI - Nutrition in cystic fibrosis: a historical overview. PMID- 1438332 TI - Energy metabolism in cystic fibrosis. PMID- 1438333 TI - Fat-soluble vitamins in cystic fibrosis. PMID- 1438334 TI - The Sir David Cuthbertson Medal Lecture 1991. The mechanisms and treatment of weight loss in cancer. PMID- 1438335 TI - Modulating the metabolic response to injury and infection. PMID- 1438336 TI - The metabolic response to cancer. PMID- 1438337 TI - Dietary manipulation of the inflammatory response. PMID- 1438338 TI - Society for Experimental Biology & Medicine. 1993. Constitution and bylaws. Membership directory. PMID- 1438339 TI - Eicosanoids: their function in renal epithelia ion transport. PMID- 1438340 TI - Intracellular localization of corticosteroid receptors in brain: potential interactions with signal transduction pathways. PMID- 1438341 TI - Chloride transport across rat ileal basolateral membrane vesicles. AB - The present study was designed to investigate Cl- transport across rat ileal basolateral membranes. Basolateral membrane vesicles were prepared by a well validated technique. The purity of the basolateral membrane vesicles was verified by marker enzyme studies and by studies of d-glucose and calcium uptake. Cl- uptake was studied by a rapid filtration technique. Neither an outwardly directed pH gradient, nor a HCO3- gradient, or their combination could elicit any stimulation of Cl- transport when compared with no gradient. 4,4 Diisothiocyanostilbene-2,2-disulfonic acid at 5 mM concentration did not inhibit Cl- uptake under gradient condition. Similarly, the presence of the combination of outwardly directed Na+ and HCO3- gradients did not stimulate Cl- uptake compared with the combination of K+ and HCO3- gradients or no HCO3- gradient. This is in contrast to our results in the brush border membranes, where an outwardly directed pH gradient caused an increase in Cl- uptake. Cl- uptake was stimulated in the presence of combined Na+ and K+ gradient. Bumetanide at 0.1 mM concentration inhibited the initial rate of Cl- uptake in the presence of combined Na+ and K+ gradients. Kinetic studies of bumetanide-sensitive Cl- uptake showed a Vmax of 5.6 +/- 0.7 nmol/mg protein/5 sec and a Km of 30 +/- 8.7 mM. Cl- uptake was stimulated by an inside positive membrane potential induced by the ionophore valinomycin in the setting of inwardly directed K+ gradient compared with voltage clamp condition. These studies demonstrate two processes for Cl- transport across the rat ileal basolateral membrane: one is driven by an electrogenic diffusive process and the second is a bumetanide-sensitive Na+/K+/2 Cl- process. Cl- uptake is not enhanced by pH gradient, HCO3- gradient, their combination, or outwardly directed HCO3- and Na+ gradients. PMID- 1438342 TI - Effect of atrial natriuretic peptide and other vasoactive compounds on the uterine vascular bed of the nonpregnant sheep. AB - It has been reported that atrial natriuretic peptide (ANP) concentrations are elevated in pregnancy and further elevated in pregnancy-induced hypertension. Atrial stretch and volume expansion appear to be important stimuli for ANP release. During normal pregnancy, a striking change in hemodynamics occurs that may increase plasma ANP concentrations. ANP has potent natriuretic, diuretic, and smooth muscle relaxant activities. The biological effects of ANP during pregnancy may play an important role in the physiology and pathophysiology of pregnancy. Because of possible interactions during pregnancy due to secondary effects of maternal cardiovascular changes and physiological adaptation, the present study sought to evaluate and characterize the local effects of atriopeptin II on the uterine vascular bed of the nonpregnant sheep. Ewes with catheters in the femoral artery, femoral vein, and uterine artery and electromagnetic flow probes on the middle uterine arteries were monitored for blood pressure (BP), heart rate (HR), and uterine blood flow before and after the administration into the uterine artery of bolus injections of 2, 4, 20, and 40 x 10(-9) M (5, 10, 50, and 100 micrograms) of the synthetic ANP (atriopeptin II). For comparison purposes, the effects of prostaglandin I2 in doses of 1.2, 2.5, 12, and 25 x 10(-8) M (5, 10, 50, and 100 micrograms), vasoactive intestinal polypeptide in doses of 3, 9, 30, 90, 300, and 900 x 10(-11) M (0.1, 0.3, 1, 3, 10, and 30 micrograms), and bradykinin in doses of 9.4, 28, 94, 280, 940, and 2800 x 10(-11) M (0.1, 0.3, 1, 3, 10, and 30 micrograms) were also tested. Appropriate vehicles were tested and found to be without effect. All four compounds were found to be vasodilators of the nonpregnant uterine vasculature. ANP administered into the uterine artery decreased BP (87 +/- 4 mm Hg to 79 +/- 4 mm Hg with 50 micrograms [20 x 10(-9) M]), increased HR (90 +/- 5 bpm to 105 +/- 4 bpm), and significantly increased uterine blood flow (from 14 +/- 3 to 37 +/- 4 ml/min with a dose of 100 micrograms [40 x 10(-8) M, P < 0.05]). Prostaglandin I2 failed to alter BP, but caused significant increases on HR (100 +/- 4 to 124 +/- 13 bpm, P < 0.05) and uterine blood flow (17 +/- 4 to 73 +/- 10 ml/min, P < 0.05). Vasoactive intestinal polypeptide caused a significant tachycardia (97 +/- 10 to 158 +/- 9 bpm, P < 0.05) at the highest dose.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1438343 TI - Hypoxic pulmonary vasoconstriction is not endothelium dependent. AB - Feline intrapulmonary arteries (mean diameter, 0.9 mm) were equilibrated in Earle's solution at constant tension in a chamber bubbled with an hyperoxic gas mixture (30% oxygen, 5% carbon dioxide, balance nitrogen). The endothelium was removed from half the vessels by gentle rubbing. The isometric response to the addition of acetylcholine (1*10(-6) M) was dilator in the vessels with endothelium and constrictor in those without endothelium. Intermittent exposure to a hypoxic gas mixture (0% oxygen, 5% carbon dioxide, balance nitrogen) for 20 min with five repetitions demonstrated sustained constrictor responses in the presence or absence of endothelium. Endothelial cells are, therefore, not required for the mediation of hypoxic pulmonary vasoconstriction. PMID- 1438344 TI - Thyroxine suppresses thrombocytopoiesis and stimulates erythropoiesis in mice. AB - Thyroxine has been shown in vitro to stimulate erythropoiesis by two mechanisms: a direct, beta 2-adrenergic receptor-mediated stimulation of red cell precursors, and an indirect, erythropoietin-mediated mechanism. Clinical reports have suggested that excess thyroxine also exerts depressive effects on thrombocytopoiesis, but the most sensitive methods of assessing platelet production, i.e., percentage of 35S incorporation into platelets and determination of megakaryocyte size and number, are not appropriate for analysis of platelet production in human patients. The purpose of this study was to use a mouse model to investigate the effects of the hyperthyroid state on erythropoiesis and thrombocytopoiesis, and to assess in vivo the two mechanisms by which thyroxine has been described to stimulate erythropoiesis in vitro. We found that thyroxine administration significantly depressed platelet production and stimulated erythropoiesis in mice. Both the D- and L-isomers of thyroxine in appropriate doses produced this depression of thrombocytopoiesis, and the effect was dose dependent for both isomers. Daily administration of thyroxine:increased blood volume; decreased the peripheral platelet count, total circulating platelet count and mass, percentage of 35S incorporation into platelets, and megakaryocyte number and size; and concurrently increased indices of red cell production (packed cell volume, red blood cell count, total circulating red blood cell count and mass, and reticulocyte count). Additionally, propranolol, a nonspecific beta blocker, partially reversed the suppression of platelet production by L thyroxine, lending credence to the assertion that the direct, beta 2-adrenergic receptor-mediated stimulation of the erythroid cell line by thyroxine reported to exist in vitro may also be important in vivo. PMID- 1438345 TI - Cytochrome P-450 pathway in renal function of normal rats and rats with bilateral ureteral obstruction. AB - Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) are decreased and mean arterial pressure (MAP) and renal vascular resistance (RVR) are increased after unilateral release of bilateral ureteral obstruction (BUO) of 24 hr duration. An imbalance between vasoconstrictor and vasodilator substances may explain these hemodynamic changes. We examined the role of the cytochrome P 450 pathway in this setting. After unilateral release of BUO, GFR and ERPF (ml/min/kg body wt) were significantly lower in these rats than in sham-operated rats (SOR) 1.14 +/- 0.09 vs 6.7 +/- 0.5 and 3.09 +/- 0.2 vs 23.5 +/- 3.4, respectively). BUO rats had significantly higher MAP (mm Hg) and RVR (mm Hg/ml/min/kg body wt) than SOR (155 +/- 5 vs 120 +/- 1 and 29.1 +/- 1.7 vs 3.2 +/ 0.4, respectively). SOR given 3-methylcholanthrene and beta-naphthoflavone to induce the cytochrome P-450 system had no significant changes in renal function, RVR, or MAP. SOR given ketoconazole to inhibit the cytochrome P-450 system had significantly lower GFR (4.8 +/- 0.5) than temporal control rats without significant changes in ERPF (21.2 +/- 4.6), MAP (127 +/- 6), or RVR (4.2 +/- 0.9). Rats with BUO given ketoconazole had lower but not significantly different GFR (0.84 +/- .1) and ERPF (2.61 +/- .4) than BUO controls. Values for MAP did not differ in BUO rats given ketoconazole versus BUO temporal controls. BUO rats given 3-methylcholanthrene and beta-naphthoflavone had significantly higher GFR and ERPF (2.01 +/- 0.24 and 6.66 +/- 1.36, respectively) and significantly lower RVR (14.7 +/- 3.9) than control rats with BUO; MAP was unchanged. Microsomal preparations from indomethacin-treated isolated kidneys obtained from BUO rats when compared with preparations obtained from SOR had significantly less activity of the P-450 cytochrome-dependent omega/omega-1 hydroxylase (103 +/- 6 vs 130 +/- 7 pmol hydroxyeicosatetraenoic acids produced per mg of protein/min, P < 0.02) and the P-450 cytochrome-dependent epoxygenase (11 +/- 0.3 vs 30 +/- 4 pmol lipoxyeicosatrienoic acids produced per mg of protein/min, P < 0.04). Indomethacin-treated microsomes prepared from kidneys of BUO rats converted significantly less 14C-arachidonic acid through the P-450-dependent hydroxylases (13.5 +/- 0.8 vs 17.0 +/- 0.1% of 14C-arachidonic acid converted to 19- and 20 hydroxyeicosatetraenoic acids, P < 0.02), and significantly less through the epoxygenases (1.4 +/- 0.4 vs. 3.8 +/- 0.5% of 14C-arachidonic acid converted to epoxyeicosatrienoic acids).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1438346 TI - Serum growth hormone levels in hypothyroid and GH-treated thyroidectomized rats and their progenies. AB - Growth hormone (GH) was measured in the sera of control, hypothyroid (thyroidectomized [Tx]) and GH-treated Tx rats and their fetuses on Days 19, 20, 21, and 22 of gestation and in their progenies on postnatal Days 1, 5, 30, and 75. Maternal endogenous serum GH increased dramatically between the 19th and 20th days of gestation and remained elevated through the 22nd day in control rats, but was depressed significantly in Tx and GH-treated Tx rats during this period. GH was not always detected in the sera of 19-day-old fetuses. On Day 20, GH was depressed in fetuses of Tx mothers as compared with those form controls or GH treated Tx mothers. GH was elevated in sera of fetuses from GH-treated Tx rats over fetuses of control and Tx only rats on the 22nd day of gestation. In postnatal rats, those from GH-treated mothers continued to show elevated serum GH on Day 1 as compared with those from Tx only mothers. On postnatal Days 5 and 30, progenies of Tx mothers had significantly elevated GH as compared with progenies of control mothers. At 75 days of age, the GH levels of these progenies had normalized. We have shown previously that the hormonal secretions of the pituitary-thyroid axis are badly disrupted in the progenies of Tx and GH-treated Tx mothers and that even as adults these animals have tissue (brain and liver) deficits of active thyroid hormones. Although the onset of GH secretion is mildly delayed in fetuses of Tx but not GH-treated Tx mothers, the serum GH levels of both groups of progenies are elevated during most of the neonatal period through the time of puberty. It is, therefore, concluded that GH in the absence of adequate levels of thyroid hormones is ineffective in preventing many of the learning and memory deficits induced in the progenies of Tx mothers. PMID- 1438347 TI - [Nursing care and the infection risk]. PMID- 1438348 TI - [Nursing service at the level of the local health unit. Organizing models]. PMID- 1438349 TI - [The working and living conditions in the nephrology and dialysis centers of the Abruzzi Region]. PMID- 1438351 TI - [World AIDS Day]. PMID- 1438350 TI - [Care for the child undergoing bronchoscopy]. PMID- 1438352 TI - [The Red Cross and the Red Crescent. The portrait of an international movement]. PMID- 1438353 TI - [Nursing education in regional Italian legal regulations, with special reference to the Lazio Region]. PMID- 1438354 TI - Protein import by yeast mitochondria. PMID- 1438355 TI - The three dimensional structure of acyl-CoA dehydrogenases. PMID- 1438356 TI - Alpha, beta-dehydrogenation by acyl-CoA dehydrogenases: role of functional groups at the active center. PMID- 1438357 TI - Identification and characterization of the 5' regulatory region of the human medium-chain acyl-CoA dehydrogenase (MCAD) gene. PMID- 1438358 TI - Molecular studies of mouse medium and long-chain acyl-CoA dehydrogenase genes for site-directed mutagenesis of embryonic stem cells. PMID- 1438359 TI - Molecular cloning and nucleotide sequence of cDNAs encoding human long chain acyl CoA dehydrogenase and assignment of its gene to chromosome 2. PMID- 1438360 TI - Pork and human cDNAs encoding glutaryl-CoA dehydrogenase. PMID- 1438361 TI - Multiple regulatory elements characterize the promoter region of the 68 kDa carnitine palmitoyltransferase in the rat and the human. PMID- 1438362 TI - The fadBA operon of Escherichia coli and evidence for the endosymbiont origin of peroxisomes. PMID- 1438363 TI - Fatty acid binding proteins: recent concepts of regulation and function. PMID- 1438364 TI - Peroxisomal and mitochondrial enzymes. PMID- 1438365 TI - The fatty acid-binding protein content and fatty acid oxidation capacity of rat tissues. PMID- 1438366 TI - Peroxisomal activation, transport and oxidation of fatty acids: implications to peroxisomal disorders. PMID- 1438367 TI - Latency of peroxisomal palmitoyl-CoA beta-oxidation in digitonin permeabilized fibroblasts: the effect of ATP on peroxisomal permeability. PMID- 1438368 TI - Resolution of the subcellular site of very long-chain fatty acid beta-oxidation in human skin fibroblasts using a novel approach. PMID- 1438369 TI - Involvement of both peroxisomes and mitochondria in the alpha-oxidation of phytanic acid. PMID- 1438370 TI - Activation and oxidation of pristanic acid in rat liver: identification of a distinct, clofibrate non-inducible pristanoyl-CoA oxidase. PMID- 1438371 TI - Role of peroxisomes in the degradation of prostaglandins. PMID- 1438372 TI - A revised pathway for the oxidation of oleic acid and odd-numbered double bond unsaturated fatty acids. PMID- 1438373 TI - Approach to the patient with a fatty acid oxidation disorder. PMID- 1438375 TI - Pathophysiological approach to carnitine palmitoyltransferase II deficiencies. PMID- 1438374 TI - Plasma and mitochondrial membrane carnitine transport defects. PMID- 1438376 TI - Neonatal carnitine palmitoyltransferase deficiency: a case with a muscular presentation. PMID- 1438377 TI - Multiple acyl-coenzyme A dehydrogenation disorders (MAD) responsive to riboflavin: biochemical studies in fibroblasts. PMID- 1438378 TI - Combined defect of long-chain 3-hydroxyacyl-CoA dehydrogenase, 2-enoyl-CoA hydratase and 3-oxoacyl-CoA thiolase. PMID- 1438379 TI - Isoenzymes of delta 3,delta 2-enoyl-CoA isomerase in rat liver. PMID- 1438380 TI - The role of tandem mass spectrometry in the diagnosis of fatty acid oxidation disorders. PMID- 1438381 TI - Detection and quantitation of acylcarnitines in plasma and blood spots from patients with inborn errors of fatty acid oxidation. AB - Acylcarnitine profiling in plasma and dried blood spots by radioisotopic exchange/HPLC demonstrates that MCAD deficiency can be reliably detected in the asymptomatic state without L-carnitine therapy. The OC/AcC ratio differentiates MCAD deficiency from normal controls. A longer chain acylcarnitine (r.t. 43 min.) was detected in all 3 patients with a defect in long chain fatty acid oxidation. Detection of C4- and C5-acylcarnitine isomers in plasma helped characterize a metabolic defect affecting branched chain acyl-CoA oxidation in 3 patients. Quantitative data in 2 patients with MCAD deficiency showed that plasma concentrations of OC and AcC are dependent on both the availability of free carnitine and the severity of metabolic decompensation. PMID- 1438382 TI - Analysis of acylcarnitines as their N-demethylated ester derivatives by gas chromatography-chemical ionization mass spectrometry: clinical applications. PMID- 1438383 TI - Treatment with docosahexaenoic acid favorably modifies the fatty acid composition of erythrocytes in peroxisomal patients. PMID- 1438384 TI - Diagnosis of inborn errors of phytanic acid oxidation using tritiated phytanic acid. PMID- 1438385 TI - Historical perspective of medium-chain acyl-CoA dehydrogenase deficiency: a decade of discovery. PMID- 1438386 TI - Peroxisomal multifunctional delta 3,delta 2-enoyl-CoA isomerase, 2-enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase enzyme from rat liver. Identity with peroxisomal bifunctional protein and proposed domain structure. PMID- 1438387 TI - Molecular analysis of medium-chain acyl-CoA dehydrogenase deficiency: a diagnostic approach. PMID- 1438388 TI - Molecular characterization of medium-chain acyl-CoA dehydrogenase deficiency causing sudden death. PMID- 1438389 TI - Insights into the topography of mitochondrial carnitine palmitoyltransferase gained from the use of proteases. PMID- 1438390 TI - Characterization of medium-chain acyl-CoA dehydrogenase (MCAD) with a point mutation associated with MCAD deficiency. PMID- 1438391 TI - Genetic heterogeneity in MCAD deficiency: frequency of K329E allele and identification of three additional mutant alleles. PMID- 1438392 TI - Medium chain acyl-CoA dehydrogenase deficiency in the United Kingdom. PMID- 1438393 TI - Frequency of G-985 mutation in medium chain acyl-coenzyme A dehydrogenase (MCAD) deficiency in sudden infant death syndrome (SIDS). PMID- 1438394 TI - Mutations causing medium-chain acyl-CoA dehydrogenase deficiency: a collaborative compilation of the data from 172 patients. Workshop on Molecular Aspects of MCAD Deficiency. PMID- 1438395 TI - Molecular analysis of disorders of peroxisomal beta-oxidation. PMID- 1438396 TI - Biochemical and molecular studies of carnitine palmitoyltransferase II deficiency with hepatocardiomyopathic presentation. PMID- 1438397 TI - Identification of the molecular defects responsible for the various genotypes of isovaleric acidemia. PMID- 1438398 TI - Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II, and identification of glycine substitution for valine 157, producing an unstable mature protein in a patient. PMID- 1438399 TI - Molecular heterogeneity of beta-ETF deficiency in glutaric aciduria type II. PMID- 1438400 TI - Human cDNA encoding ETF dehydrogenase (ETF:ubiquinone oxido-reductase), and mutations in glutaric acidemia type II. PMID- 1438401 TI - Molecular basis of 3-ketothiolase deficiency. PMID- 1438402 TI - Thermodynamic studies of medium-chain acyl-CoA dehydrogenase complexed to thioether-CoA ligands. PMID- 1438403 TI - Purification of long-chain 3-hydroxyacyl-CoA dehydrogenase from human infant liver. PMID- 1438404 TI - Peroxisomal biogenesis in Saccharomyces cerevisiae. PMID- 1438405 TI - Evolution of the acyl-CoA dehydrogenase/oxidase superfamily. PMID- 1438406 TI - Purging with 4-hydroperoxycyclophosphamide combinations. PMID- 1438407 TI - Graft-versus-leukemia reactions following bone marrow transplantation for chronic myeloid leukemia. PMID- 1438408 TI - Prevention of graft-versus-host disease by using immunotoxins. PMID- 1438409 TI - Purging multidrug resistant cells from bone marrow. PMID- 1438411 TI - Neuroblastoma purging by immunorosette depletion. PMID- 1438410 TI - Peanut agglutinin purging and magnetic microspheres. PMID- 1438412 TI - Autologous bone marrow transplantation after in vitro purging with monoclonal antibodies and complement in acute lymphoblastic leukemia. PMID- 1438413 TI - Factors limiting the efficiency of immunomagnetic cell separation. PMID- 1438414 TI - Large-scale immunomagnetic separation system for the removal of tumor cells from bone marrow. PMID- 1438415 TI - Successful autologous transplantation of immunomagnetic bead purged bone marrow in non-Hodgkin's lymphoma. PMID- 1438416 TI - Autologous bone marrow transplantation for acute leukemia using ferromagnetic microparticles and monoclonal antibody-purged marrows: demonstration of effectiveness by polymerase chain reaction. PMID- 1438417 TI - Purging of acute lymphoblastic leukemia by long-term marrow culture. PMID- 1438418 TI - Bone marrow purging with antisense oligodeoxynucleotides. PMID- 1438419 TI - Molecular approaches to purging of chronic myelogenous leukemia marrow in autologous transplantation. PMID- 1438420 TI - Positive selection of cell subpopulations using a high gradient magnetic field system. PMID- 1438421 TI - Colloidal magnetite-bound blood cells: their potential in separation technology. PMID- 1438422 TI - Use of etoposide in combination with cyclosporine for purging multidrug resistant leukemic cells from bone marrow in a mouse model. PMID- 1438423 TI - Marrow purging: present status and future perspectives--efficacy in AML. PMID- 1438424 TI - Autologous bone marrow transplantation for advanced neuroblastoma. PMID- 1438425 TI - Autologous bone marrow transplantation with in vitro chemotherapy purge in first remission of acute myeloid leukemia. PMID- 1438426 TI - Bone marrow purging in patients with refractory cancer. PMID- 1438427 TI - Immunomagnetic purging in autologous bone marrow transplantation: experience in fourteen patients. PMID- 1438428 TI - GM-CSF administration enhances granulocytic recovery in purged autologous bone marrow transplantation for acute lymphoblastic leukemia. PMID- 1438429 TI - Salvage and transfusion of autologous red blood cells from bone marrow harvest. PMID- 1438430 TI - A simple method to detect immature hemopoietic progenitors after in vitro treatment with ASTA-Z 7654. PMID- 1438431 TI - Use of licensed electrolyte solutions and anticoagulant citrate dextrose for bone marrow collection. PMID- 1438432 TI - Analysis of variations in cryomedium and methods of freezing on human bone marrow stem cells. PMID- 1438433 TI - Expanding role of the bone marrow processing laboratory. PMID- 1438434 TI - Incidence of bacterial contamination of bone marrow grafts. PMID- 1438435 TI - Selective depletion of CD8-positive T-lymphocytes for allogeneic bone marrow transplantation: engraftment, graft-versus-host disease and graft-versus leukemia. PMID- 1438436 TI - Campath-1M antibodies for T cell depletion of haploidentical marrow transplanted to children with malignant osteopetrosis. PMID- 1438437 TI - Immunomagnetic depletion of CD8+ lymphocytes from marrow grafts. PMID- 1438438 TI - Effects of mafosfamide on the clonogenic cells in precursor B acute lymphoblastic leukemia: significance for ex vivo purging of bone marrow. PMID- 1438439 TI - The combined use of elutriation and CD8/magnetic bead separation to engineer the bone marrow allograft. PMID- 1438440 TI - Graft versus host tolerance in dogs across one DLA-haplotype by depletion of CD6 positive cells. PMID- 1438441 TI - New technology for the depletion of T cells from soybean lectin agglutinated, HLA matched bone marrow grafts for leukemia: initial laboratory and clinical results. PMID- 1438442 TI - CD48 monoclonal antibody K31 for bone marrow transplantation. PMID- 1438443 TI - Effects of ex vivo treatment with methylprednisolone and vincristine on bone marrow lymphohematopoietic cells. PMID- 1438444 TI - Detection of occult lymphoma cells in bone marrow aspirates by multi-dimensional flow cytometry. PMID- 1438446 TI - Detection of minimal residual breast cancer in bone marrow. PMID- 1438445 TI - In vitro effects of Ilmofosine on acute lymphoblastic leukemia cells and on normal hemopoietic cells. PMID- 1438447 TI - Deferoxamine as a purging agent for autologous bone marrow grafts in neuroblastoma. PMID- 1438448 TI - Alkyl-lysophospholipid purging for autologous bone marrow transplantation in acute leukemia in second or subsequent remission after extramedullary relapse. PMID- 1438449 TI - Efficacy of purging clonogenic leukemia cells using ether lipid and hyperthermia for autologous bone marrow transplantation. PMID- 1438450 TI - Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow. PMID- 1438451 TI - Search for new antiviral agents of plant origin. PMID- 1438452 TI - Antimicrobial activity of naphtoquinones and Allium extracts combined with antibiotics. AB - Combinations of antibiotics and known antimicrobial natural products, naphtoquinones and Allium extracts, were investigated. The chessboard broth method was applied to assess the activity of these combinations against aerobic and anaerobic bacteria. If no antagonism was observed, the combinations studied lead from partial to total synergism, mainly against aerobic bacteria. PMID- 1438453 TI - Antioxidants in some pharmaceuticals, cosmetics and food from the European market. AB - A specific and sensitive reverse phase HPLC method (AO-1) for the quantitative determination of ten phenolic antioxidants and propyl paraben in fatty products (food, pharmaceuticals and cosmetics) has been developed. Extraction with acetonitrile from a hexane dilution of the products; acetic acid-water acetonitrile-methanol solvent system and detection at 280 nm and quantification by internal standard procedure (reference compound: DMP, dimethylphenol) were used. Good resolutions for all peaks, especially BHT and DG, and no interferences with others common additives were achieved. Mean recoveries, by addition of standards to sample at 20, 50 and 100 micrograms/g, were 96-101% (BHT, 84-86%); minimal quantifiable levels were 0.5-1.6 micrograms/g. Two simple isocratic methods for the confirmation of data obtained by AO-1 were also developed: AO-2 for seven phenolic antioxidants and propyl paraben with DMP as internal standard, AO-3 for four lipophilic antioxidants with di-tert-butylphenol (DTBP) as internal standard. PMID- 1438454 TI - Parasympathomimetic activity of salpantiol. A new cyclitol from Salpianthus arenarius. AB - A new cyclitol was isolated using the flowers of the Salpianthus arenarius, and its chemical structure was determined (2-methoxy-5hydroxymethyl cyclopentane 1,3,4-triol). The contractile effects of acetylcholine (Ach), Atropine, Pilocarpine, Adrenaline and Cyclitol were studied in rat ileum. Such cyclitol proves to have parasympathomimetic activity. PMID- 1438455 TI - [Optimization of liberation of theophylline derivatives from Gelucire matrix tablets]. AB - Matrix tablets containing theophylline, etofylline, dyphylline and proxyphylline were prepared with saturated polyglycolysed glycerides whose melting point was 50 degrees C and HLB were 2 and 13 (Gelucires 50/02 and 50/13), in order to eliminate the melting point influence and to have extreme values of HLB. The influence of two parameters was studied: HLB of the mixtures of Gelucires and drug solubility. Drug release was found to increase as these two parameters rose, the main factor being HLB value. Multiple linear regression was used to evaluate their influence. The mathematical model obtained was employed to optimize the release of each active ingredient from the tablets made of mixtures of the two Gelucires with HLB ranging from 3 to 4 depending on drug solubility. PMID- 1438456 TI - [Synthesis and pharmacology of structural analogs of tienilic acids]. AB - Three structural analogs of tienilic acid were synthetized and evaluated for their diuretic activity in the rat. Two compounds are alpha substituted tienilic acid derivatives by an alkylated group. The third one is a conformationally restricted derivative through a cyclization process. All compounds fall to increase the urinary flow in the pharmacological assay. PMID- 1438457 TI - [The adverse effects of local anesthetics on the eye in the development of ocular irritation test]. AB - Referring to the ocular damage produced by local anaesthetics applied to the eye, the authors suggest the use of a test, to reveal the danger that some ophthalmic preparations may represent for patients. They review the studies devoted to the evaluation of ocular damage, particularly those which resulted into tests based on the methodology of Draize. A test scaled down to the mouse eye is described, in which the subjective appreciation is completed by an objective measurement. The test is based on the increased permeability of injured cornea for fluorescein. The fluorescence emitted by this tracer depends on the extent of the micro-lesions and is measured with an optical electronic device. The possibilities and limitations of this test are determined by the relationship between dose and extent of ocular damage. Such a relationship has been established for oxybuprocain. An appropriate concentration of this local anaesthetic allows to investigate the influence of adjuvants, preservatives and viscosifiers on the effect of oxybuprocain on the cornea. The authors conclude that it is possible to apply this test to the development of well-tolerated ophthalmic preparations. PMID- 1438458 TI - [Microbial contamination of twenty drugs of plant origin]. AB - Twenty drugs of plant origin were analysed in order to determine the microbial contamination level. A light homogenizing method was used to avoid an increase in the antimicrobial capacity of certain drugs, which would falsify the analytical results. The total viable aerobic count (TVC) varied from 10(1) to 10(7) CFU/g and in 11 samples out of 21 was equal to or higher than 10(5) CFU/g. The number of fungi varied from one drug to another, but was generally lower than the aerobic TVC to the power of 10. No cases containing Aspergillus flavus were found. The total viable anaerobic count consisted mainly of facultative anaerobic germs. Aerobic spores and facultative anaerobic bacteria were abundant. They often represented more than 50% of the aerobic TVC and among them, Bacillus cereus was found. Concerning specified micro-organisms, Escherichia coli was found 3 times, Staphylococcus aureus 2 times and Pseudomonas (not aeruginosa) a few times. Salmonella was never found. The Enterobacteriaceae, on the other hand, were often found and in some cases their number can be greater than 10(4) CFU/g. The typed bacteria corresponded to Enterobacter spp. Some drug samples in bags were analysed. The level of contamination was identical to that found in the bulk drugs. The analysis in parallel of a black tea sample showed an aerobic TVC of 4.10(3) CFU/g. Specified micro-organisms were not found in the infusions. In comparison with non-boiled drugs, the survivors can represent up to 30% of the aerobic TVC. PMID- 1438459 TI - [Adhesion of Pseudomonas aeruginosa to human buccal epithelia cells and the effect of protamine on their attachment]. PMID- 1438460 TI - Isolation and mass spectrometric identification of cyclosporin A isomeric dihydrodiol precursors from erythromycin-induced rabbit liver microsomes. PMID- 1438461 TI - Improvement of clonazepam release from a Carbopol hydrogel. AB - The performance of Tween 80, Tween 60, oleic acid, oleyl alcohol and Azone as enhancers of clonazepam permeation from a Carbopol hydrogel through a cellulose nitrate membrane was investigated. The effect of incorporating methyl beta cyclodextrin (DS 1.8) in combination with clonazepam as a solid phase into some vehicles was also tested. In vitro release studies were carried out with a Sartorius apparatus and the following parameters were evaluated: drug solubility in the vehicle; partition coefficient of the drug between lauryl alcohol (the solvent which impregnates the membrane) and the vehicle; steady state flux; permeability constant; diffusion coefficient; lag time. The release kinetics followed a nearly zero-order pattern, although the diffusion-controlled mechanism might also have been operative. Maximum drug release (2.5 times that of the gel base) was achieved for the formulation containing clonazepam and methyl beta cyclodextrin in a 1:1 (mol/mol) ratio as a solid phase, in a vehicle composed of water, propylene glycol, Tween 80 and Azone at a mass fraction of 43%, 50%, 2% and 5%, respectively. PMID- 1438462 TI - Biological activities and mechanisms of action of PGJ2 and related compounds: an update. PMID- 1438463 TI - Modifications of platelet phospholipid fatty acid composition in streptozocin induced diabetic rats. AB - Increased thromboxane A2 (TXA2) generation by platelets has been reported both in diabetic patients and streptozocin-induced diabetic rats. This increase is in contrast to the decreased prostacyclin (PGI2) synthesis by endothelial cells in diabetes. An imbalance in the ratio of TXA2/PGI2 has been implicated in increased platelet aggregation and a high incidence of vascular disease in human diabetes. The mechanism for this imbalance, however, remains elusive. In a previous study from our laboratory, we reported unchanged arachidonic acid levels in platelet membrane phospholipids of 3-week diabetic rats, but a decreased arachidonic acid level in platelet membrane phospholipids of 6-week diabetic rats. In the present communication, we report the role of enzymes that are involved in remodeling arachidonic acid levels of platelet membrane phospholipids in both 3- and 6-week diabetic rats. No alterations were observed in the activities of arachidonoyl-CoA synthetase, acyl-CoA: lysophosphatidylcholine acyltransferase, or phospholipase A2 in platelets from both 3- and 6-week diabetic rats. However, both increased uptake and incorporation of [14C]arachidonic acid into platelets were observed in the diabetic platelet-rich plasma. In conclusion, increased TXA2 formation in diabetic platelets is not due to alterations in the activities of enzymes involved in the incorporation into or release of arachidonate from the diabetic platelet membrane phospholipid, but may be due to increased efficiency of uptake, incorporation or possibly redistribution of this fatty acid among phospholipid classes in diabetic platelets. PMID- 1438464 TI - Peritoneal macrophages from patients on continuous ambulatory peritoneal dialysis show a differential secretion of prostanoids and interleukin-1 beta. AB - In vitro secretion of the prostanoids PGE2 and PGI2 and of the cytokine IL-1 beta by peritoneal macrophages obtained from CAPD patients during episodes of peritonitis and infection free periods, was determined, after culturing with or without 5 micrograms/ml of LPS. The release of PGE2 and PGI2 as measured by its stable metabolite 6-keto-PGF alpha was determined in 10 episodes of peritonitis and 10 infection free periods. IL-1 beta release was determined in 14 episodes of peritonitis and 20 infection free periods. PGI2 release from macrophages declined sharply during peritonitis both in the absence and presence of LPS in the culture medium (p less than 0.005). A tendency to decreased PGE2 release was found during peritonitis, when macrophages were cultured in the absence of LPS. In the presence of LPS, the same amounts of PGE2 were released during peritonitis and during an infection free period. On the other hand, peritoneal macrophages released significantly more IL-1 beta during peritonitis as compared to an infection free period, provided that the cells were in vitro stimulated with LPS. In view of the interregulatory effects between prostanoids and macrophage cytokines in their production, these findings may indicate that the impaired release of PGI2 during peritonitis has allowed the macrophages to secrete more IL 1 beta after in vitro stimulation with LPS. This implies that PGI2 and PGE2 may play a distinct role in the regulation of cytokine secretion by these cells. PMID- 1438465 TI - Bradykinin and not cholecystokinin stimulates exaggerated prostanoid release from the inflamed rabbit gallbladder. AB - The relationship of bradykinin and cholecystokinin (CCK) to inflamed gallbladder prostanoid synthesis and release was examined in rabbits treated with common bile duct ligation (BDL) for 24 or 72 h. Gallbladders removed from control and BDL groups were incubated in oxygenated Krebs buffer at 37 degrees C (pH 7.4) for 60 min. The slices were then placed every 20 min in vials containing increasing doses of bradykinin (30-3000 ng) or CCK (30-1000 ng). Incubation fluid was analyzed by RIA for 6-keto-prostaglandin (PG)F1 alpha (PGI2 metabolite), PGE2 and thromboxane (TX) B2. Bradykinin stimulated control gallbladder 6-keto-PGF1 alpha and PGE2 release was modest. Gallbladders from 24- and 72-h BDL groups released 3 to 10-fold higher levels of 6-keto-PGF1 alpha and PGE2 (not TXB2) following bradykinin stimulation when compared to controls, which was abolished with indomethacin pretreatment. CCK did not stimulate gallbladder prostanoid release in the control or BDL groups. These data show that bradykinin and not CCK stimulated PGI2 and PGE2 release from inflamed rabbit gallbladder. Increased BDL gallbladder PGI2 release may be prolonged or augmented by bradykinin as gallbladder distention and progressive acute inflammation stimulate local bradykinin formation. PMID- 1438466 TI - Effect of a newly synthesized leukotriene antagonist, (E)-2,2-diethyl-3'-2-2-(4 isopropyl) thiazolyl ethenyl succinanilic acid (MCI-826), on immunological liver injury and nephritis in mice. AB - The effect of a newly synthesized leukotriene antagonist, (E)-2,2-diethyl-3'-2-2 (4-isopropyl) thiazolyl ethenyl succinanilic acid (MCI-826), on liver injury and nephritis in mice was studied. In order to confirm the anti-leukotriene activity of MCI-826, the effect of MCI-826 on leukotriene C4(LTC4)- and leukotriene D4(LTD4)-induced vasculitis, liver and kidney injury was studied. MCI-826 was found to clearly inhibit LTC4- and LTD4-induced vasculitis, as well as liver and kidney injury. In addition to LT-induced reactions, MCI-826 inhibited liver injury induced by injection of either an anti-basic liver protein antibody into DBA/2 mice that had been previously immunized with rabbit IgG or of a bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated DDY mice. Moreover, MCI-826 inhibited nephritis, caused by injecting antiglomerular basement membrane antibody into C57BL/6 mice. These results suggest that MCI-826 can be applied to the treatment of certain tissue inflammatory diseases. PMID- 1438467 TI - Prostaglandin E production by uteri of ovariectomized pregnant rats receiving antiprogesterone steroid or in which progesterone has been withdrawn. AB - Antiprogesterone steroid, ZK98299 (Schering, Germany) or RU38486 (Roussel Uclaf, France), has been administered to ovariectomized early pregnant rats receiving continuous steroid replacement. At 24 h later, uterine explants of rats treated with ZK98299 produced significantly greater amounts of prostaglandin E (PGE) than did controls or animals treated with RU38486. The PGE/PGF2 alpha production ratio for uteri of rats treated with ZK98299 or RU38486 was markedly lowered compared to controls, and a significant decrease occurred in the PGE/6-keto PGF1 alpha production ratio for rats treated with RU38486. For ovariectomized early pregnant rats in which progesterone has been withdrawn, a significant reduction in uterine PGE production occurred when compared to control animals. There was also a marked decrease in PGE/PGF2 alpha production ratio, and the PGE/6-keto PGF1 alpha production ratio tended to be lowered relative to controls. The stimulated production (as by ZK98299) or unchanged production of PGE (as by RU38486) indicates a selective action on uterine PGE synthesis among the antiprogesterone steroids, and these findings cannot be explained simply in terms of a blockage of progesterone receptors. PMID- 1438468 TI - Suppression of hepatic prostaglandin F2 alpha in rats by dietary alpha-tocopherol acetate is independent of total hepatic alpha-tocopherol. AB - Groups of eight weanling female F344/N rats were fed semipurified diets that supplied 0, 50, 500, 5000, or 15,000 mg alpha-tocopherol acetate/kg diet, with and without 0.05% phenobarbital (PB) for 9 weeks. Both plasma and hepatic alpha tocopherol levels, measured by HPLC, strongly correlated with alpha-tocopherol intake (r greater than 0.73, p less than 0.0001). Phenobarbital both depleted hepatic alpha-tocopherol and increased plasma alpha-tocopherol significantly. Although treatment with PB for 9 weeks significantly increased GST activity, PB did not affect hepatic prostaglandin (PG)F2 alpha status, as determined by radioimmunoassay. PGF2 alpha was significantly greater (by 52%) in rats fed no alpha-tocopherol than in rats fed 15,000 mg alpha-tocopherol acetate/kg diet. Hepatic PGF2 alpha status was correlated inversely but weakly with dietary alpha tocopherol (r = -0.24, p less than 0.05). Hepatic PGF2 alpha status was not correlated with hepatic or plasma alpha-tocopherol status. This finding suggests either that there is a small depletion-resistant subcellular alpha-tocopherol pool which regulates PGF2 alpha production or that alpha-tocopherol alters PGF2 alpha production in vivo by an indirect mechanism. PMID- 1438469 TI - The regulation of prostaglandin biosynthesis in cells derived from human gestational tissues: effects of fetal calf serum. AB - We have evaluated the production of prostaglandin E2 (PGE2) and its regulation in amnion, chorion, and decidual cells in the presence and absence of fetal calf serum (FCS), and in the absence of FCS but with supplementation with substrate arachidonic acid (AA). Basal rates of PGE2 biosynthesis in amnion, chorion and decidual cell cultures were significantly reduced in the absence of FCS. The magnitudes of the responses to various stimulatory agents were different between cells from different tissues and the different culture media. We conclude that these different experimental conditions must be taken into account when interpreting the results of such in vitro experiments. PMID- 1438470 TI - The role of eicosanoids in the kidney damage induced by Candida albicans. AB - A major target organ in generalized candidiasis is the kidney. The purpose of this study was to investigate the role of eicosanoids in the kidney infected by proteinase-positive and proteinase-negative Candida albicans. Prostaglandin (PG) E2-like activity was found to be significantly decreased while leukotriene (LT) C4-like activity increased within 10 days in the kidneys of mice infected with C. albicans. These results indicate that arachidonic acid metabolism is shifted to the lipoxygenase pathway and lipid peroxides, produced via this enzyme system may play an important role in the kidney damage induced by C. albicans. PMID- 1438471 TI - Some secondary plant metabolites in Desmodium adscendens and their effects on arachidonic acid metabolism. AB - The effects of three chemically different groups of compounds, (triterpenoid saponins, beta-phenylethylamines and tetrahydroisoquinolines), known to be present in Desmodium adscendens, on plasma membrane ion channel, cytochrome P450 NADPH-dependent oxygenation of arachidonic acid, and production of prostaglandins by the cyclooxygenase enzyme system, are described. The very high-conductance calcium-activated potassium ion channel, which is responsible for the maintenance of tone in smooth muscles, was activated by the saponins. The cytochrome P450 NADPH-dependent monooxygenase reaction, which produces epoxy- and hydroxylated eicosanoids from arachidonic acid metabolism, was inhibited by an analogue of the tetrahydroisoquinoline present in the plant. This analogue also acted as a reductant in the prostaglandin synthesizing system using microsomes from ram seminal vesicles. The same system was activated by the beta-phenylethylamines found in the plant material, with the formation of more prostaglandins, the type being dependent on the amount of cyclooxygenase enzyme used and the presence or absence of coenzyme. PMID- 1438472 TI - [The color of alkyl-diammonium-rhodizonate]. PMID- 1438473 TI - [Phytoalexins and their significance for the resistance of higher plants to harmful organisms]. PMID- 1438475 TI - Effects of neonatal monosodium glutamate and aging on morphine dependence development. AB - Administration of monosodium glutamate (MSG) to neonatal rats has been reported to destroy aspartatergic (ASPergic) and glutamatergic (GLUergic) neurons. Ageing has been shown to induce cell loss, a rather general CNS atrophy, and slowness in the CNS functions. On the other hand, it has been hypothesized that two of the main reasons for opiate dependence development are the blockade by opiates of the NMDA receptors and their associated upregulation and supersensitivity. Accordingly, the abstinence syndrome precipitating effect of naloxone (NL) has been assumed to be the consequences of the removal by NL of opiate from NMDA receptors without being able to prevent upregulated and supersensitive NMDA receptors from being stimulated stronger than normal. To investigate the role of the decrease in the number of NMDA receptors in the development of morphine (M) physical dependence, 4 g/kg MSG was SC injected into neonatal rats on days 2, 4, 6, 8 and 10 after birth. Their littermate controls SC received equimolar NaCl solution. Three or 14 months later, three pellets containing 75 mg base M were SC implanted into male rats treated neonatally with MSG or equimolar NaCl solution. Seventy-two hours after pellet implantation, all rats were injected with 2 mg/kg NL intraperitoneally. Some abstinence syndrome signs were counted or rated for 15 min immediately after NL injection and then statistically evaluated. The NL precipitated abstinence syndrome was less intense in 3-month-old MSG-treated rats than in controls, most probably due to the decrease in the number of NMDA receptors in MSG-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438474 TI - Behavioural responses to amphetamine and apomorphine in pigs. AB - The effects of different doses of amphetamine (0-1.5 mg/kg) and apomorphine (0 1.0 mg/kg) on behaviour of pigs were compared. Amphetamine induced an increase in levels of nosing and rooting and of locomotion. These increases were, however, related to increased levels of standing. At higher doses (1.0-1.5 mg/kg), amphetamine specifically induced a rigid standing posture with jerking head and limb movements. Apomorphine at 0.1-1.0 mg/kg increased locomotion. In contrast to amphetamine, this effect was specific as it was not explained by increased levels of standing. At 1.0 mg/kg, apomorphine specifically induced "locomotion while the pigs maintained snout contact with the floor or trough." In addition, at this dose it induced drinking in one test, while licking in another. These differences may in part be due to differences in the test environment. Apomorphine exerted a strong conditioning effect, as indicated by the lack of behavioural variability in the postinjection period. This effect may explain the large interindividual variation in apomorphine response. Amphetamine and apomorphine elicit different behavioural syndromes in pigs, suggesting that they act on different neural systems. In addition, neither amphetamine nor apomorphine elicited behaviour that closely resembles environmentally induced stereotypies. PMID- 1438476 TI - Relationship between amphetamine and environmentally induced stereotypies in pigs. AB - The study investigated the relationship between the behavioural response to a standard dose of amphetamine and environmentally induced stereotypies in pigs. There were large individual differences in the frequency of amphetamine-induced stereotypies and time spent in locomotion. In addition, these two measures tended to be negatively correlated to each other, indicating that they were competitive. Levels of amphetamine stereotypies were negatively correlated with those of chain manipulation and drinking after a period of 50 and 100 days of physical restraint and food restriction; levels of locomotion were positively correlated with levels of chain manipulation after 100 days of restraint and restrictive feeding. These results suggest that pigs differ in their predisposition to develop environmentally induced stereotypies, and that this is related to catecholaminergic systems in the brain. In an amphetamine test performed after the period of restraint and restrictive feeding, amphetamine stereotypies were generally higher than in the first test but behaviour was no longer correlated to previous levels of environmentally induced stereotypies. The qualitative differences between the two forms of stereotypy, their negative rather than positive correlation, and the lack of correlation between environment-dependent stereotypies and stereotypies in the second amphetamine test suggests a complex relationship between these two forms of stereotypies. The increased amphetamine sensitivity in the second amphetamine test may reflect the effect of stress on central catecholaminergic systems. PMID- 1438477 TI - Prevention of learned helplessness: in vivo correlation with cortical serotonin. AB - Learned helplessness (LH) is prevented by pretreatment with acute benzodiazepines (BDZs), subchronic tricyclic antidepressants (TCAs), or escapable stress (ES). We have investigated the role of serotonin (5-HT) in LH prevention by these three prevention paradigms, using microdialysis to measure in vivo 5-HT release in frontal cortex (FC) after LH testing. Rats receiving pretreatment before inescapable stress with any of the three methods of prevention--BDZs, TCAs, or ES -showed escape behavior in the shuttle-box test for LH comparable to naive unstressed controls. K(+)-stimulated 5-HT release in all three groups receiving pretreatment was also similar to naive unstressed controls. Rats receiving saline before inescapable stress showed significantly more LH behavior in the shuttle box task and had significantly lower 5-HT release as well. This suggests that LH correlates with a significant decrease in intracellular releasable 5-HT in FC, and that three different techniques for LH prevention, acute BDZs, subchronic TCAs, and ES all similarly prevent this 5-HT depletion. PMID- 1438478 TI - Genetic differences in the development of physical dependence upon diazepam in Lewis and Fischer 344 inbred rat strains. AB - The purpose of the present study was to investigate physical dependence upon diazepam systematically in two inbred strains of rats, Lewis (LEW) and Fischer 344 (F344). Rats were chronically fed food containing diazepam on an escalating drug dosage schedule, from 1 and 2 to 12 mg/g of food, over a period of 30 days. During treatment, the growth curve in LEW and F344 rats was suppressed compared with the respective controls. Motor incoordination was evaluated by a rotarod performance test. The ranking of the motor incoordination during the final concentration of diazepam was as follows: F344 greater than LEW. After substitution of normal food for the diazepam-admixed food, various signs of diazepam withdrawal occurred 16-120 h later. These signs included vocalization, irritability, muscle rigidity, ear-twitching, Straub's tail, piloerection, fascicular twitch, tremor, convulsion, and death. The incidences of vocalization, ear-twitching, piloerection, and tremor in F344 were significantly higher than those in LEW rats. Furthermore, two of six F344 rats showed spontaneous convulsions and one rat died of convulsions. Overall withdrawal scores were significantly greater in F344 (16.0) than in LEW (6.3) rats. These results suggest that diazepam withdrawal severity is strongly influenced by genetic factors, and F344 rats are highly susceptible to dependence upon benzodiazepines. PMID- 1438479 TI - Cocaine and regional brain monoamines in mice. AB - Cocaine HCl (0, 10, or 50 mg/kg) was injected into adult male ICR mice IP. Thirty minutes later, brains were removed and nine regions were isolated: olfactory bulbs (OB), olfactory tubercles (OT), prefrontal cortex (PC), septum (SP), striatum (ST), amygdala (AMY), hypothalamus (HT), hippocampus (HC), and thalamus (TH). Using high-performance liquid chromatography, concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their major metabolites were determined. At 10 mg/kg cocaine, NE levels were increased in the AMY and its metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), was decreased in the PC, AMY, and HT. DA levels were also increased in the AMY, while its intracellular metabolite, dihydroxyphenylacetic acid (DOPAC), was decreased in the ST and its extracellular metabolite, homovanillic acid (HVA), was decreased in the PC. 3 Methoxytyramine (3-MT) levels were not altered in any tissue. 5-HT levels were increased in the AMY, HT, and TH, while its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was decreased in the OB and ST. MHPG/NE ratios were decreased in the PC, AMY, and HT as were those for HVA/DA. DOPAC/DA ratios were decreased in the ST and AMY and increased in the SP while those for 3-MT/DA were decreased in the TH and increased in the PC. 5-HIAA/5-HT ratios were decreased in the AMY, HC and TH. At 50 mg/kg cocaine, there was an increase in DA in the TH. There was a decrease in DOPAC, HVA, and 3-MT, as well as the DOPAC/DA ratio in the ST. In the OT, there was a decrease in DOPAC, the DOPAC/DA ratio, 3-MT, and the 3-MT/DA ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438480 TI - Indomethacin and sodium carbonate effects on conditioned fever and NK cell activity. AB - The augmentation of natural killer (NK) cell activity and elevation of body temperature (fever) can both be conditioned using camphor odor as the conditioned stimulus (CS) and poly I:C as the unconditioned stimulus (US). While both responses can be conditioned in parallel fashion as shown previously, our results indicate the conditioned learning of these responses may not follow along a common path. We found that injection of a 1% solution of sodium carbonate was able to consistently block the CS/US learning of the NK cell response but did not block conditioning of the fever response. In contrary fashion, mice treated with indomethacin (which inhibits prostaglandin-induced fever) dissolved in the sodium carbonate solution did not learn in consistent fashion the fever response. However, indomethacin-treated animals were able to recall the NK cell response. These results support the view that although the same mediator, IFN-beta, is responsible for the conditioned learning of the NK cell and fever responses both the learning and recall of the responses are initiated along separate pathways. PMID- 1438481 TI - Effect of yohimbine on the reproductive behavior of the male Nile crocodile Crocodylus niloticus. AB - The effect of yohimbine, an alpha 2-adrenergic blocker, on the reproductive activity of 12-year-old male, captive Nile crocodiles was tested on 18 animals equally divided into 3 ponds. In each pond, there were 6 males and 30 females. In the first group, six of six males received yohimbine capsules of 30 mg, twice a day, for 1 week. In the second group, two males of a group of six were administered a similar dose of yohimbine. Another group of six males in a separate pond were used as a control group. The yohimbine treatment had a significant (p less than 0.05) effect on the frequency of headslap display (the main behavioral pattern of reproductive activity) in all treated animals but did not result in a significant increase in copulation frequency. In the two treated groups, the reproductive period was prolonged by 3 weeks, 8-11 weeks. We found a significant increase in the fertility percentage of eggs laid by females in the male-treated groups (30.5% in control group females, 34.1% in the partly treated, and 39.0% in the pond where all six males were treated), even though no increase in mating frequencies was noted. This might be due to more successful copulations. During the treatment period, the daily activity peak, when the male's headslap performance was the most frequent, was shifted from 5:00-6:00 p.m. in the control to 4:00-5:00 p.m. in the treated group. This effect caused females to enter the water earlier than in the control group. PMID- 1438482 TI - Effects of lesions of the central nucleus of the amygdala on anxiety-like behaviors in the rat. AB - The effects of lesions of the central nucleus of the amygdala on anxiety-like behaviors in the rat were determined using two animal models, the conditioned suppression of drinking (CSD) and defensive burying paradigms. For CSD conflict testing, water-restricted rats were trained to drink water from a tube that was occasionally electrified (0.25 mA); electrification was signaled by a tone. CSD test sessions were 10 min in duration and were conducted 4 days per week. After at least 3 weeks of conflict testing, both punished (30-40 shocks per session) and unpunished (10-12 ml water per session) responding had stabilized. Subjects then received bilateral electrolytic lesions of the central nucleus of the amygdala or sham lesions. After a 1-week recovery period, CSD conflict testing was reinstated and continued for 20 weeks. Amygdaloid-lesioned subjects accepted significantly more shocks than did sham controls. In addition, acute challenges with the benzodiazepine chlordiazepoxide (2.5-10 mg/kg, IP, 30-min pretreatment), the barbiturate phenobarbital (20 mg/kg, IP, 10-min pretreatment), and carbamazepine (10 mg/kg, IP, 10-min pretreatment) produced an increase in punished responding in both amygdaloid-lesioned and sham-treated subjects. Analysis of covariance (ANCOVA)-based adjusted means for the change in shocks received were not significantly different between the two groups. Following completion of the CSD studies, subjects were tested in the defensive burying paradigm. Although there was no significant difference between lesioned and sham treated subjects on the percent of animals that exhibited burying, subjects with lesions of the central nucleus of the amygdala exhibited a significantly greater latency to initiate defensive burying.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438483 TI - Lack of effect of social context on the reinforcing effects of diazepam in humans. AB - The reinforcing effects of diazepam (DZP) were compared under two conditions in human volunteers using a cumulative dose procedure. Under the social (SOC) condition, groups of two to four subjects participated concurrently whereas in the solitary (SOL) condition subjects participated individually. During the first four sessions of each condition, subjects received 20 mg DZP in five divided doses (4 mg) in two of the sessions and placebo (PL) in the other two sessions. Each drug (DZP or PL) was administered in a distinctively colored capsule and labeled by letter code. During the last three choice sessions, subjects chose which capsule they wished to self-administer and were allowed to choose up to a maximum of seven capsules (28 mg DZP) during each session. Subjects also filled out questionnaires that assessed momentary mood. Overall, DZP was chosen on 33% of choice sessions and there were no differences across conditions. There was a tendency for choice to be correlated with levels of weekly alcohol consumption and liking scores, and as well the latter two measures were correlated. DZP produced sedative-like subjective effects that did not appear to be related to setting, choice of drug in the study, or alcohol drinking history. These results partially confirm previous reports of a relationship between DZP preference and alcohol consumption, but differ from previously reported studies in the overall lower level of DZP choice. PMID- 1438484 TI - Age-dependent changes in serotonergic modulation of yawning in the rat. AB - Serotonin (5-HT) effects on physostigmine (PHY)-induced yawning were studied in LY Sprague-Dawley rats by injecting Lu 10 171 (citalopram), a specific 5-HT uptake blocker, and two antagonists--methiothepine and ritanserin--which differ slightly in the selectivity of their actions on different 5-HT receptor subtypes. Infant and young rats show significant increases in PHY-induced yawning when preinjected with citalopram (5-10 mg/kg). Two-month-old animals show this effect only with 10 mg/kg. With adult animals (3-5 months old), the effect is the opposite: Yawning decreases. The facilitory effect in infant and young rats was counteracted by methiothepine but not by ritanserin, suggesting that it is mediated through 5-HT1A or 5-HT1B receptor subtypes. The inhibitory effect of citalopram in adult rats was unmodified by the two antagonists used, leaving open the possibility that it is mediated by 5-HT3 receptors. PMID- 1438485 TI - Effects of MK 801 on morphine physical dependence: attenuation and intensification. AB - It has previously been reported that the noncompetitive NMDA receptor antagonists ketamine and dextromethorphan suppressed the naloxone-induced morphine abstinence syndrome. In addition, the previous blockade by ketamine and dextromethorphan of NMDA receptors has been shown to intensify the naloxone-elicited morphine abstinence syndrome. On the basis of this information, another noncompetitive NMDA receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo-a,d-cyclohepten 5,10-imine maleate (MK 801), was administered to rats in which two morphine containing (75 x 2 morphine base) pellets had been implanted. The naloxone precipitated abstinence syndrome in rats injected with 0.3 mg/kg MK 801 36 h after pellet implantation was found significantly more intense than controls whereas the abstinence syndrome in rats that received 0.1 mg/kg MK 801 before naloxone injection was less intense. The intensification by MK 801 given 36 h following pellet implantation was attributed to the further increase in upregulation and supersensitivity of NMDA receptors caused by morphine. The attenuation was explained by the blockade by MK 801 of NMDA receptors as occurred in the case of ketamine and dextromethorphan. PMID- 1438486 TI - Opposite actions of oxytocin and vasopressin in the development of cocaine induced behavioral sensitization in mice. AB - Subchronic administration of cocaine induces behavioral sensitization (increasing hypermotility) to a challenge dose of the drug administered 72 h after the cessation of treatment. The effects of repeated administration of the neurohypophyseal hormones oxytocin (OXT) and arginine8-vasopressin (AVP) on the development of behavioral sensitization induced by subchronic treatment with cocaine were investigated in mice. Repeated treatment of OXT and AVP did not modify the locomotor stimulatory effect of the challenge dose of cocaine in cocaine-naive control animals. OXT in a dose of 0.5 microgram (sc) augmented the cocaine-induced behavioral sensitization. In contrast, AVP (0.005-0.5 microgram/mouse, sc) dose dependently attenuated the development of sensitization to the hypermotility-inducing effect of cocaine. The results suggest that the behavioral sensitization induced by cocaine can be modulated in opposite directions by neurohypophyseal hormones. PMID- 1438487 TI - Effects of the preferential dopamine autoreceptor antagonist (+)-AJ76 in the intracranial self-stimulation paradigm. AB - As revealed by locomotor activity experiments in rodents, cis-(1S,2R)-5-methoxy-1 methyl-(2-n-propylamino)tetralin [(+)-AJ76] is a preferential dopamine autoreceptor antagonist that produces stimulatory or weak inhibitory behavioral effects in animals that display low or high baseline activity, respectively. In the present study, the possible positive reinforcing properties of (+)-AJ76 were studied by means of the intracranial (median forebrain bundle) self-stimulation (ICSS) technique in rats. The current intensity of the electrical stimuli was used as the independent variable. The resulting rate/intensity curves were analyzed by computer, and the half-maximal response (called EC50) was calculated for each animal. When starting on a suprathreshold current intensity, (+)-AJ76 dose dependently (3.1-52.0 microM/kg, SC) increased the EC50 without producing any apparent motor deficits like muscular rigidity or catalepsy. A clear-cut and more potent inhibitory action was also noted for haloperidol (0.033-0.133 microM/kg, SC) and the di-N-methyl analog of (+)-AJ76 called (+)-AJ118 (0.8-3.5 microM/kg, SC), while d-amphetamine (1.4 or 5.4 microM/kg, SC) decreased the EC50 values. In the second experiment, animals were subjected to a subthreshold current intensity for 30 min. The intensity was set to produce a response of 15% or less of maximal, shaping response rate for the respective animals. Of these 22 animals, 10 responded with a stimulation, while the ICSS response was inhibited in the others. We did not, however, get consistent results in all rats tested. In summary, this study shows that (+)-AJ76 appears to lack positive reinforcing properties comparable to those produced by classical stimulants such as d amphetamine. PMID- 1438488 TI - Effects of cocaine and ethylcocaine on schedule-controlled responding in rats. AB - The effects of cocaine and benzoylecognine ethyl ester (ethylcocaine), its metabolite found only in simultaneous users of cocaine and ethanol, were studied in rats responding for food under a multiple fixed-ratio fixed-interval schedule of food presentation. Both cocaine and ethylcocaine increased rates of responding under the fixed-interval component and decreased the quarter life. Both drugs only decreased rates of responding under the fixed-ratio component. Cocaine was approximately equipotent to ethylcocaine. Ethylcocaine may contribute to interactions between cocaine and ethanol by exerting cocaine-like effects not seen with other cocaine metabolites. PMID- 1438489 TI - Relationships between ingestion and gustatory perception of caffeine. AB - We observed that taste detection thresholds for caffeine (CAF) are elevated in habitual CAF users relative to nonusers. A series of experiments were carried out to explore that relationship and assess the influences of salivary CAF and acute vs. chronic CAF ingestion. A significant correlation between CAF ingestion and taste threshold was noted in two studies of U.S. adults, although this was not observed in a parallel study involving an Argentinean population. Acute CAF ingestion (5.5 mg/kg) had no appreciable effect on taste thresholds. Threshold values greatly exceeded even peak salivary CAF levels, indicating that classical taste adaptation was an unlikely influence. Chronic CAF ingestion (450 mg/day for 3 weeks) also had no consistent effect on taste thresholds for CAF or other taste stimuli. Although a number of explanations are considered, we suggest that the sensory phenomenon may reflect preexisting differences between CAF users and nonusers or perhaps an effect of exposure to other bitter and/or CAF-containing foods and beverages. PMID- 1438490 TI - Steroid levels in tadpole (Rana catesbeiana) brain at the loss and return of the righting response. AB - Steroid levels were determined at the onset of anesthesia (tLRR) and at the recovery from anesthesia (tRRR). When 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha) was the administered agent, 3 alpha levels were similar at tLRR and tRRR1. The net rate of uptake of 3 alpha by the brain was approximately eight times the rate of loss of 3 alpha. Levels of 3 alpha were twice as high as tLRR when progesterone (PG) was the administered agent as when 3 alpha was used. The presence and absence of 0.1% ethanol in the incubation bath had no detectable effect on steroid levels. A model for the actions of 3 alpha is described. It is argued that interactions between 3 alpha and the target site are specific with respect to chemical structure and that the amount of 3 alpha in the compartment that contains the target sites is always small compared to that in whole brain. PMID- 1438491 TI - Influence of prenatal maternal stress on the immunocompetence of the offspring. AB - To evaluate the effects of prenatal maternal stress on the development of humoral immunocompetence in the offspring and on their hormonal and immunologic responses to postnatal stress, gravid Sprague-Dawley rats were exposed daily on gestational days 15-21 to prenatal environmental stress [(PES) 15 unsignaled, inescapable electric foot-shocks (0.05 mA for 0.5 s)] or prenatal psychological stress [(PPS) pregnant rats were placed in the nonelectrified section of the apparatus and allowed to see, hear, and smell a nonpregnant partner being environmentally stressed]. Pregnant controls (PC) were placed in the apparatus for 30 min. Serum corticosterone (CCS) and immunoglobulin G (IgG) levels were measured in the offspring every 7 days from birth to postnatal day (PND) 28. On PND 29-33, offspring were environmentally stressed; hormonal and immune status were determined on PND 34. Levels of IgG were reduced in PES and PPS offspring on PND 0 and in PES offspring on PND 7 and 28. These changes were unrelated to differences in CCS and did not reflect altered maternal-pup interactions or nutritional factors. Postnatal stress was immunosuppressive in PC pups but did not alter immune parameters in PPS offspring. In PES females, postnatal stress was also immunosuppressive. However, in PES males with already reduced IgG levels postnatal stress enhanced immune function. These data provide the first experimental evidence that prenatal maternal stress can alter immune parameters in the rat offspring. PMID- 1438492 TI - Effects of chronic administration and withdrawal of antidepressant agents on circadian activity rhythms in rats. AB - Experimental and clinical studies indicate that clinical depression may be associated with disturbances of circadian rhythms. To explore the interaction between circadian rhythmicity, behavioral state, and monoaminergic systems, the present study investigated the effects of chronic administration and withdrawal of the following antidepressant agents on circadian wheel-running rhythms of laboratory rats: a) moclobemide, a reversible and selective monoamine oxidase (MAO) type A inhibitor; b) Ro 19-6327, a selective MAO type B inhibitor; c) desipramine, a preferential norepinephrine reuptake inhibitor; d) clomipramine and e) fluoxetine, both serotonin reuptake inhibitors; and f) levoprotiline, an atypical antidepressant whose biochemical mechanism is still unknown. Wheel running activity rhythms were studied in three inbred strains of laboratory rats (ACI, BH, LEW) under constant darkness (DD). Two of these inbred strains (BH and LEW) show profound abnormalities in their circadian activity rhythms, namely, a reduced overall level of activity and bimodal or multimodal activity patterns. Chronic treatment with moclobemide and desipramine consistently increased the overall level, as well as the circadian amplitude, of the activity rhythm. Furthermore, the abnormal activity pattern of the LEW strain was changed into a unimodal activity pattern like that of other laboratory rats. The free-running period tau was slightly shortened by moclobemide and dramatically shortened by desipramine. Effects of moclobemide and desipramine treatment on overall activity level and duration were reversed shortly after termination of treatment, whereas long aftereffects were observed for the free-running period. All other substances tested had no systematic effects on the activity rhythms of any of the strains. The fact that moclobemide and desipramine altered the period, amplitude, and pattern of circadian activity rhythms is consistent with the hypothesis that monoaminergic transmitters play a significant role in the neuronal control of behavioral state and circadian rhythmicity. Although the present study found that some antidepressives affect parameters of circadian rhythmicity, it could not demonstrate a common effect of all classes of antidepressives. PMID- 1438493 TI - Self-administration of pentobarbital in light and moderate alcohol drinkers. AB - Preference for a moderate dose of pentobarbital was assessed in light and moderate alcohol drinkers using a double-blind, placebo-controlled laboratory choice procedure. Sixteen light drinkers (less than six alcoholic drinks per week) and 13 moderate drinkers (six or more drinks per week) participated in a seven-session study in which they first sampled capsules containing pentobarbital (150 mg) or placebo and then chose and ingested the capsule they preferred. Subjective and behavioral measures were obtained at regular intervals during each session to characterize the drug's effects. Both groups chose pentobarbital less often than placebo: Mean pentobarbital choice in light drinkers was 20.8% and in moderate drinkers was 38.5%. Pentobarbital choice and drug liking ratings were highest among male moderate drinkers but still did not exceed placebo levels. The drug did not increase scores on standardized measures of drug euphoria, even among the most frequent choosers or the heaviest alcohol consumers. The results extend previous reports showing that individuals without histories of drug abuse, even those who are moderate consumers of alcohol, do not self-administer sedative/anxiolytic drugs or experience their effects as euphorigenic. PMID- 1438494 TI - Pharmacological properties of ceruletide in the vertical and horizontal locomotor activities of mice. AB - To clarify the pharmacological properties of ceruletide (CER) and cholecystokinin octapeptide (CCK-8) with respect to vertical (VLA) and horizontal (HLA) locomotor activities of mice, effects of pretreatment with CER (0.5, 5, and 50 micrograms/kg, IP) and CCK-8 (5, 50, and 500 micrograms/kg, IP) on apomorphine (0.1 mg/kg, SC)- and clonidine (0.1 mg/kg, SC)-induced hypo-VLA and -HLA and on apomorphine (1 mg/kg, SC)-induced hyper-VLA and -HLA were examined. CER and CCK-8 had a dose-dependent inhibitory effect on VLA and HLA in intact mice. Pretreatment with CER had a biphasic effect (increase and decrease) on apomorphine- and clonidine-induced hypo-VLA, as well as an effect on apomorphine induced hypo-HLA, a decreased effect on clonidine-induced hypo-HLA, and a decreased effect on apomorphine-induced hyper-VLA and -HLA. On the other hand, pretreatment with CCK-8 had no effect on apomorphine- and clonidine-induced hypo VLA and -HLA and a decreased effect on apomorphine-induced hyper-HLA but not on hyper-VLA. These results suggest that for apomorphine- and clonidine-induced locomotion in mice CER has pharmacological properties different from those of CCK 8. PMID- 1438495 TI - Effect of ambient temperature on the paradoxical metabolic responses to norepinephrine. AB - Four experiments were conducted to examine the effect of ambient temperature (Ta) on norepinephrine (NE)-induced metabolism. NE increased oxygen consumption at ambient temperatures above and at acclimation temperature and decreased oxygen consumption at ambient temperatures below acclimation temperature in both nonacclimated (25 degrees C) and cold-acclimated (5 degrees C) rats. Varying the Ta between -5 degrees and 25 degrees C at a fixed dose of NE (250 micrograms/kg, IP) resulted in a temperature-dependent decrease in metabolism in nonacclimated rats as a function of Ta. A similar effect was demonstrated in cold-acclimated rats tested at -15, 5, and 25 degrees C. Varying the dose of NE between 100 and 1,000 micrograms/kg at a Ta of 25 degrees C resulted in a maximal thermogenic response at a dose of 250 micrograms/kg with diminished responsiveness at higher and lower doses. At 5 degrees C, NE inhibited metabolism maximally at a dose of 250 micrograms/kg. Propranolol, a nonspecific beta-antagonist, attenuated the hypometabolic effect of NE in the cold, while the alpha 2-antagonist yohimbine completely blocked this effect. These results suggest that the metabolic suppressive effect of NE may be mediated by the presynaptic alpha 2-receptor and that beta-adrenoceptors may also contribute to this effect. PMID- 1438496 TI - Effects of oral ethanol self-administration on the inhibition of the lever-press response in rats. AB - The effects of ethanol on the inhibition of a learned response were examined in adult, male Wistar rats from two treatment groups: oral self-administration of alcoholic solution (10% ethanol and 10% glucose in distilled water) and oral self administration of sweet solution (10% glucose in distilled water). Subjects were food deprived and alcoholic or control solutions were available 1 h per day during 15 days. After this period, rats were tested in a two-bottle paradigm during 1 h per day and placed in the operant chambers immediately afterward. This phase went on for 19 days. Subjects were trained to lever press for food and were tested in a continuous reinforcement schedule, operant extinction, successive discrimination, and two-stimuli tests. Alcohol impaired the ability to inhibit previously reinforced responses but only in situations indicated by exteroceptive stimuli. Ethanol intake did not impair the lever-press behavior neither in the acquisition of the response nor in the continuous reinforcement schedule. These data suggest that the sedative effects of alcohol at this dose were not apparent in reinforcement situations, in contrast with extinction situations. PMID- 1438497 TI - Glycinergic interventions potentiate the ability of MK 801 to raise the threshold voltage for tonic hindlimb extension in mice. AB - Milacemide, an acylated prodrug of glycine, was able to increase the efficacy with which [+]-5-methyl-10,11-dihydro-5h-dibenzo[a,d]cyclohepten-5,10-imine meleate (MK 801) antagonized the electrical precipitation of seizures in mice. The mechanism of milacemide's potentiation of MK 801's antiseizure efficacy in intact mice is unclear; however, a glycine agonist selective for the strychnine insensitive site on the NMDA receptor complex was also able to potentiate MK 801. The exciting possibility exists that an exogenous glycinergic intervention can potentiate NMDA-mediated neural transmission in intact animals. PMID- 1438498 TI - Failure of cholecystokinin antagonists to modify the discriminative stimulus effects of cocaine. AB - Enhancement of brain dopamine (DA) activity is believed to be an important mechanism underlying the discriminative stimulus effects of cocaine in animals and the subjective effects of cocaine in people. Cholecystokinin (CCK) receptors, which are colocalized with DA receptors in several brain regions, have been implicated as modulators of DA activity, leading to speculation that CCK-based drugs might be developed as therapeutics for cocaine abuse. In the present study, the effects of cocaine alone and after pretreatment with the selective CCKA antagonist devazepide and the selective CCKB antagonist CI 988 were determined in squirrel monkeys trained to discriminate cocaine (1.0 mg/kg) from saline. When tested alone, cocaine engendered dose-related increases in the percentage of cocaine-appropriate responses, reaching virtually exclusive responding on the cocaine-associated lever after doses of 1.0 mg/kg or greater. Pretreatment with a wide range of doses of either devazepide (0.01-3.0 mg/kg) or CI 988 (0.3-30 mg/kg) did not systematically alter the discriminative stimulus effects of any dose of cocaine. The results do not support a role for CCK antagonists in the pharmacotherapy of cocaine abuse. PMID- 1438499 TI - Long-term suppression of the development of complementary memory storage sites in mice: functional interdependence of acetylcholine and dopamine. AB - Bitemporal injections of puromycin consistently induce amnesia of aversive maze learning in mice when given within 3 days after training. These injections consistently fail to induce amnesia when given 6 or more days after training. Consistent with the evidence from other laboratories, we interpret these results to indicate that the initial, temporal memory storage sites are supplemented 6 days after training by the development of complementary storage sites in other cerebral areas. Previous experiments have shown that this process is suppressed for 30-60 days by a single SC injection of scopolamine, a muscarinic antagonist. We now find that this suppressive action of scopolamine can be completely nullified by haloperidol, a dopaminergic antagonist. This finding supports the view that there may be a therapeutic role for dopamine antagonists in the treatment of cognitive dysfunction associated with cholinergic loss. PMID- 1438500 TI - Potential pharmacodynamic effect of charcoal on theophylline neurotoxicity in normal rats. AB - Previously, it has been found that repeated oral administration of activated charcoal (AC) to rats with renal failure markedly decreased the sensitivity of the CNS to the neurotoxic-convulsant effect of theophylline. The present study was designed to investigate whether this effect also occurs in normal rats. Normal rats received AC per os in either a single dose or in six doses every 8 h. Control animals received equal volumes of water. Two hours following the last AC dose, animals were infused IV with theophylline until the onset of maximal seizures. Although rats pretreated with repeated administrations of activated charcoal required a larger total theophylline dose to induce convulsions, the theophylline concentrations in the serum and brain at the onset of the neurotoxic episode were not affected by the charcoal pretreatment. It is, therefore, concluded that the gastrointestinal dialysis produced by the activated charcoal had no apparent effect on theophylline-induced neurotoxicity in normal rats. PMID- 1438501 TI - Comparative effects of ethanol on motor activity and operant behavior. AB - Ethanol effects on two types of motor activity and on lever responding for food delivered on a fixed-ratio 20 (FR 20) reinforcement schedule were compared using C57BL/6 (C57) mice. Low doses of ethanol (1-2 g/kg) transiently elevated horizontal activity and high doses (2.5 and 3.0 g/kg) reduced this behavior throughout testing with a slight recovery toward the end of a 16-min test period. In contrast, similar ethanol doses produced a monotonic reduction in both vertical activity and lever responding for food under the FR 20 schedule. The ethanol-induced reduction in FR 20 lever responding was less prolonged than the reduction in vertical activity but was more prolonged than the reduction in horizontal activity. Because vertical activity and lever responding for food delivered on the FR 20 schedule were never elevated, were reduced at ethanol doses that either stimulated or depressed horizontal activity, and were unaffected by low ethanol doses that did not affect horizontal activity, it is unlikely that either are sensitive to the stimulatory effects of ethanol. Accountable mechanisms for the different effects of ethanol on the three behaviors are unknown; however, the present study eliminates ethanol dose, postinjection time, testing time, and food deprivation condition as possible reasons for the differences. PMID- 1438502 TI - Anxiogenic properties of cocaine in the rat evaluated with the elevated plus maze. AB - In previous work, we reported that cocaine (5, 10, and 20 mg/kg) failed to induce significant responses in naive rats in the elevated plus-maze test of anxiety. This study investigates the putative anxiogenic properties of cocaine in rats selected as "anxious" or "nonanxious" on the basis of their behavior in the plus maze prior to drug treatment. In nonanxious rats, cocaine (10 mg/kg) increased the latency to the first entry into the open arms and reduced the number of entries into and time spent on the open arms. All these measures are indicative of an anxiogenic action of cocaine. In contrast, cocaine failed to modify the behavior of anxious rats. These findings demonstrate that rats with high exploratory activity in the plus-maze and regarded as nonanxious are more sensitive to cocaine's anxiogenic effects. Further, the present manipulation provides a useful procedure for investigating the anxiogenic effects of cocaine in rats. PMID- 1438503 TI - Vitamin B12 improves cognitive disturbance in rodents fed a choline-deficient diet. AB - The effect of vitamin B12 on learning disturbance was tested in rats. Rats were fed a choline-enriched, choline-deficient, and choline-deficient diet with vitamin B12. Concentrations of acetylcholine in the brain were significantly lower in rats fed a choline-deficient diet than rats fed a choline-enriched diet. Passive avoidance learning shows that rats on a choline-deficient diet showed significantly impaired learning compared to rats on a choline-enriched diet. However, there was no significant difference of acetylcholine in the brain or in the passive avoidance learning between rats fed a choline-enriched and a choline deficient with vitamin B12 diet. We, therefore, suggest that vitamin B12 potentiates learning in an acetylcholine-deprived brain. PMID- 1438504 TI - Acute alcohol intoxication, body composition, and pharmacokinetics. AB - The present study compared alcohol pharmacokinetics associated with body weight, anthropometrically estimated total body water, and body mass index in men and women in two experimental sessions, single dose and double dose. All subjects were given the same amount of alcohol (2.3 and 4.6 oz. 86 proof vodka for single dose and double dose, respectively). Data analyses found a significant correlation between body mass index and peak blood alcohol concentration (BAC). Weight and total body water were not significantly correlated with peak BAC. The findings suggested that body mass index may be considered a better criterion than body weight for equating alcohol doses. PMID- 1438505 TI - Differential effects of scopolamine on working and reference memory depend upon level of training. AB - Controversy exists whether the cholinergic system in the brain is involved in working memory (WM) selectively or in both WM and reference memory (RM). Rats were trained to obtain food from four baited arms of an eight-arm radial maze. The remaining arms were never baited. Three types of errors were recorded: entry into unbaited arms (RM errors), reentry into baited arms (WM errors), and reentry into unbaited arms (WRM errors). There were no differences among three control conditions: methyl scopolamine, physiological saline, and uninjected. Scopolamine increased WM but not RM errors. When rats were trained to a higher criterion of learning, however, both WM and RM were impaired. It appears that when baseline error rate is sufficiently low RM errors under scopolamine become observable. The results suggest that the cholinergic system is involved in both WM and RM, and the selective involvement of WM is the result of insufficient training. The controversy in the literature over the involvement of the cholinergic system in WM and RM was addressed. PMID- 1438506 TI - Inhibitory influence of morphinans on ictal and interictal EEG changes induced by cortical application of penicillin in rabbits: a comparative study with NMDA antagonists and pentobarbitone. AB - The effects of dextrorphan (DX) and dextromethorphan (DM) were tested using the electroencephalogram (EEG) and behavioral effects induced by topical cortical application of penicillin in rabbits. For comparison, the influence of the NMDA antagonists, dizocilpine (MK 801) and 3-((+-(-)2-carboxypiperazine-4-yl)propyl-1 phosphonic acid (CPP), and of pentobarbitone was investigated. Intracortical injection of 500 IU of penicillin produced an EEG spiking followed by a repeated generalization of the electrical and behavioral symptoms. Within a few minutes, DX (5-15 mg/kg, IV) or pentobarbitone (5-10 mg/kg, IV) reduced dose dependently and significantly (p less than 0.01) the interictal and ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin. Higher doses of pentobarbitone (20 mg/kg, IV) but not of DX (20 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin. Within a few minutes, MK 801 (0.1-0.2 mg/kg, IV) or CPP (10-20 mg/kg, IV) reduced dose dependently and significantly (p less than 0.01) the ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin, while they did not affect the penicillin-induced interictal EEG changes. Higher doses of MK 801 (0.3 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin. Within a few minutes, DM (10-20 mg/kg, IV) blocked the behavioral effects, but failed to affect either the interictal or the ictal EEG effects induced by cortical injection of 500 IU of penicillin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438507 TI - Scopolamine increases nonreinforced behavior in an intracranial self-stimulation discrimination paradigm. AB - The effects of several doses of systemic scopolamine administration on brain stimulation reward from the A10 nucleus of the ventral tegmental area (VTA) were evaluated. The intracranial self-stimulation (ICSS) task involved a two-hole nose poke procedure allowing for the assessment of both reinforced (correct) and nonreinforced (incorrect) performance levels as a function of varying current intensities. Scopolamine (0.75, 1.5, and 3.0 mg/kg) was found not to alter the rate-intensity functions derived from descending and ascending presentation of seven current levels. However, when nonreinforced behavior was considered significant increases in error responding were evident following scopolamine injection. These results are consistent with the known disinhibitory and perseverative properties of scopolamine, and indicate that the previously reported positive actions of peripheral administration of anticholinergic drugs on ICSS likely involved a drug-induced rate-enhancement of reward-unrelated performance variables. PMID- 1438509 TI - [Synthesis of thieno(3,3-d)- and -(3,4-d)pyrimidines by alternative ring closure reactions]. AB - 3-Acetylamino-substituted thiophene with cyano and carboxylic acid methylester group in 2- and 4-position react with primary amines to give thieno(3,2-d)- or thieno(3,4)-dpyrimidines. Furthermore thieno(3,4-d)-pyrimidines were prepared from non-acetylated thiophene derivatives. Some thienopyrimidines showed antiulcer antiallergic effects, respectively. PMID- 1438508 TI - Synthesis, hypotensive and diuretic activities of several 3-hydrazino-5,6 dihydrobenzo[h]cinnolines. Part 10: Pyridazine derivatives. PMID- 1438510 TI - Oxidation of brefeldin A. AB - Oxidation of the macrolide antibiotic brefeldin A with pyridinium chlorochromate adsorbed on alumina afforded [6S, 10E, 11aS, 14E]-6-methyl-2,3,6,7,8,9,11a,12 octahydro-4 H-cyclopent[f]oxacyclotridecin-1,4,13-trione together with 13 oxobrefeldin. These compounds showed higher cytotoxic activity on P388 leukemia cells than brefeldin A, brefeldin A-1,13-diacetate, brefeldin A-13-acetate, tetrahydrobrefeldin or tetrahydrobrefeldin-1,13-dione. 13-Oxobrefeldin exceeded brefeldin A in antifungal activity on Candida albicans. PMID- 1438511 TI - Partitioning behaviour of local anesthetic fomocaine derivatives. AB - The octanol/water partitioning behaviour of local anesthetic fomocaine derivatives has been investigated. The true partition coefficients obtained from log P(app) values reflect well the high lipophilicity of these aminoalkylaryl ether type compounds. A consequence of this is that the partitioning of the protonated form is not negligible as was proved by the log P(i) values of the ionized molecule measured at pH 4.0. The effect of ionization on partitioning was studied and characterized by the pQ values. This ionization influence on lipophilicity was found quite constant (pQ approximately 4) among the hydroxypiperidine analogs. A parabolic relationship was obtained between the acute toxicity and the log P values of several of the examined compounds. PMID- 1438512 TI - Bioavailability of two formulations of acetylsalicylic acid gums. AB - Bioavailability studies have been performed with ten healthy volunteers on different dosage forms of acetylsalicylic acid (ASA) in order to assess the bioavailability of two different ASA gums compared with commercial ASA tablets. The results of this study show that ASA is more readily absorbed and eliminated after administration of gum formulations than after administration of tablets, but the bioavailability obtained from the gums was lower than that observed from the tablets. PMID- 1438513 TI - [Mucus models for investigation of intestinal absorption mechanisms. 2. Mechanisms of drug interactions with intestinal mucus]. AB - Using in vitro models previously described [1] mucus retention and mucus diffusion of polar and non-polar drugs were measured. It could be shown that drug interaction with pig intestinal mucus was based on non-specific binding. The pH dependence of retention by mucus does not confirm electrostatic interaction of drugs with mucus but favour drug distribution to hydrophobic areas within the mucus. High lipophilicity and retention by mucus correlate with low diffusion of drugs through mucus. PMID- 1438514 TI - Effects of the nootropic AWD 52-39 on the blood-brain transfer of leucine, choline and glucose in rats after 14-d exposure to ethanol. AB - The transport of the neutral amino acid L-leucine as well as of choline and D glucose across the blood-brain barrier (BBB) of male Wistar rats was studied after 14-day exposure to ethanol and treatment with the nootropic drug AWD 52-39 (1). After ethanol exposure the half-saturation constant (Km) and the maximum velocity of transport (Vmax) declined in the majority of the investigated brain regions. Also, the treatment elicited a regionally different increase of the permeability-surface area (PS) product of choline (between 10% and 33%) and glucose (between 12% and 27%). The changes in the blood-brain transfer of the three compounds were diminished or prevented by additional application of 1. The cerebral blood flow was increased by the exposure to ethanol by maximally 44%. After additional administration of 1 the changes were reversed and the blood flow reached control values. In addition, the activity of the enzyme acetylcholine esterase was determined in the striatum and the hippocampus. After ethanol exposure the enzyme activity declined by 32%. It was less diminished after treatment with 1. The latter effects let assume that the changes of the BBB permeability elicited by ethanol and 1 are related to alterations of brain metabolism. PMID- 1438515 TI - [Effects of valerian root oil, borneol, isoborneol, bornyl acetate and isobornyl acetate on the motility of laboratory animals (mice) after inhalation]. AB - The aromatherapeutical use of commercial valerian root oil (Chinese origin) and of pure fragrance compounds--borneol, isoborneol, bornyl acetate (main constituent of the proved valerian root oil) and isobornyl acetate--as potentially drugs with sedative effects after inhalation was investigated in an animal experiment (mice). In additional analyses the mice were treated i.p. by caffeine and distinct sedative effects were observed only by inhalation of the cited substances. PMID- 1438517 TI - [Kentjur--a little-known asiatic spice and medicinal plant]. AB - Detailed description of the morphological and anatomic characteristics of Indian originating Kentjur plant (Kaempferia galanga L., Zingiberaceae family) which is cultivated in Java and the Sudan. In case of suspected falsification of the Kentjur powder by other Zingiberaceae rhizome powders or their starches it is difficult to differentiate. The quality determining components are described as well as the utilization as spice and medicinal herb. PMID- 1438516 TI - [Activity of new iminium compounds against bacteria and fungi. 28. Synthesis of 1 ethyl-, 1-n-dodecyl-2-phenyl-3-(n-alkylthiomethyl)- and 1-ethyl-, 1-n-dodecyl-2 phenyl-3-(n-alkoxymethyl)imidazolium chlorides]. AB - The synthesis of quaternary imidazolium compounds was performed by reaction of 1 ethyl- or 1-n-dodecyl-2-phenylimidazole with chloromethyl-n-alkyl ether or chloromethyl-n-alkyl sulfid. The antibacterial properties of the compounds obtained were tested on 13 strains of bacteria and fungi. 1-Ethyl-2-phenyl-3-(n decylthiomethyl)-, 1-ethyl-2-phenyl-3-(n-dodecylthiomethyl)imidazolium chloride and 1-n-dodecyl-2-phenyl-3-(n-butylthiomethyl)-, 1-n-dodecyl-2-phenyl-3-(n hexylthiomethyl)imidazolium chloride indicated the best antibacterial activity. PMID- 1438518 TI - [Solid phase extraction for GC detection analysis of isosorbide dinitrate and glycerol nitrate in human plasma]. PMID- 1438519 TI - Analysis of clotrimazole in ointments by high-performance liquid chromatography. PMID- 1438520 TI - The determination of ofloxacin in tablets by potentiometry and conductometry. PMID- 1438521 TI - Definition of pharmacological receptors. PMID- 1438522 TI - In vivo evidence that ethosuximide is a substrate for cytochrome P450IIIA. AB - The role of various subfamilies of rat hepatic cytochrome P450 in the oxidation of ethosuximide was evaluated by comparing ethosuximide clearance in control rats and those pretreated with relatively selective P450 inducers and/or inhibitors. Clotrimazole pretreatment increased ethosuximide clearance threefold (p less than 0.005). Dexamethasone increased ethosuximide clearance twofold (p less than 0.001), and the dexamethasone effect was completely abolished by a single dose of triacetyloleandomycin. These results suggest a prominent role for cytochrome P450IIIA in ethosuximide metabolism in the rat. Isoniazid increased ethosuximide clearance twofold (p less than 0.001), and this effect was abolished by a single dose of diallylsulfide, suggesting that ethosuximide is also processed by cytochrome P450IIE1 in rats. Phenobarbital pretreatment increased ethosuximide clearance 2-2.7 fold (p less than 0.001); an effect that was only partially reversed by orphenadrine, an inhibitor of cytochrome P450IIB/IIC enzymes. This suggests a quantitatively less important role for the IIB/IIC subfamilies in processing ethosuximide, since phenobarbital is an inducer of P450 subfamilies IIB, IIC, IIE, and IIIA. Neither the cytochrome P450IA inducer, beta naphthoflavone, nor the inhibitor, alpha-naphthoflavone altered ethosuximide clearance. Ajmaline, an inhibitor of cytochrome P450IID, had no effect on ethosuximide clearance. Together, these findings suggest that ethosuximide is principally oxidized by cytochrome P450IIIA, and that cytochrome P450IIE may play an important role. Cytochromes P450IIB/C play less prominent roles in ethosuximide oxidation, and neither cytochrome P450IA nor cytochrome P450IID is involved. PMID- 1438523 TI - Pharmacokinetics of pyrazinoyl-guanidine, 3-aminopyrazinoyl-guanidine and their corresponding pyrazinoic acid metabolites in humans and dogs. AB - Pyrazinoylguanidine (PZG), 3-aminopyrazinoylguanidine (NH2PZG) and their pyrazinoic acid metabolites were measured by a new reverse-phase HPLC method in the serum of dogs and humans after administration of PZG, NH2PZG or 2-pyrazinoic acid (PZA). Kinetic properties of PZG and its principal metabolite, PZA, were studied in normal humans and also in azotemic patients, since PZG acts on renal tubules of patients with kidney failure to increase urea elimination. In humans and dogs, PZG was rapidly hydrolyzed to PZA. The serum half-life (t1/2) of PZG was 1 h. In turn, PZA was metabolized to 5-hydroxy-PZA, but no evidence appeared for conjugation of PZA with glycine. The apparent volume of distribution of PZG and its 3-amino analog, NH2PZG, exceeded that of total body water. In the dog the serum t1/2 for NH2PZG was twice that of PZG. Compared to PZG, NH2PZG and its metabolite, 3-aminopyrazinoic acid, were much stabler in vitro in serum and water. PMID- 1438524 TI - Activated astrocytes, but not pyramidal cells, increase glucose utilization in rat hippocampal CA1 subfield after ischemia. AB - The local cerebral glucose utilization (CMRglc) in the damaged rat hippocampal CA1 subfield increases 7 days after 10 min of cerebral ischemia. We have used the N-methyl-D-aspartate antagonist (NMDA antagonist) ketamine in rats 7 days after sham operation or cerebral ischemia to determine whether the elevated postischemic CMRglc of the CA1 subfield is due to long-lasting hyperexcitation of surviving or injured neurons, or, alternatively, to the metabolism of other cell types. The autoradiographic data were interpreted with the aid of histochemical analysis of the postischemic hippocampal cell changes. Anesthetic doses of ketamine significantly reduced the CMRglc in the CA1 strata oriens, pyramidale and radiatum of sham-operated rats, while the postischemic increases in CMRglc in these hippocampal CA1 strata were not affected by ketamine. In addition, there were ketamine-induced increases in the CMRglc of the CA1 stratum lacunosum moleculare of both sham-operated and postischemic rats. The immunoreactivity of the microtubule-associated protein 2 (MAP2), a postsynaptic protein marker, was decreased markedly in the CA1 subfield in postischemic rats, while the presynaptic protein marker, synaptophysin, remained the same in sham-operated and postischemic rats. The glial fibrillary acidic protein (GFAP) immunoreactivity of astrocytes raised markedly in the ischemically damaged CA1 subfield. Although it could be demonstrated that presynaptic terminals remain intact in the postischemic damaged CA1 subfield, the lacking ketamine effect on CA1 pyramidal neurons indicated that the increase in CMRglc in this brain area is not due to postsynaptic neural hyperexcitation, but probably has to be attributed to astrocytes activated by neuronal damage. PMID- 1438525 TI - Sulphydryl-containing agents stimulate the healing of duodenal ulceration in man. AB - This prospective randomized double-blind study examined whether sulphydryl containing agents stimulate the healing and prevent the recurrence of duodenal ulceration in man. To this end, DL-methionine methyl sulphonium chloride (MMSC, 500 mg four times daily) or DL-cysteine (200 mg four times daily) were orally administered with cimetidine. Symptomatic endoscopy-proven duodenal ulcer patients who were smokers and social drinkers were randomized to receive for 8 weeks cimetidine (400 mg b.d.), cimetidine (400 mg b.d.) with MMSC, or cimetidine (400 mg b.d.) with cysteine. These patients were then kept on their respective oral regimens (except for cimetidine which was changed to 400 mg at bedtime) for 1 year (maintenance) and followed up for another. After 8 weeks of treatment, the ulceration healed in 65 patients (74%) given cimetidine alone but in all the patients given MMSC (n = 87) or cysteine (n = 86) with cimetidine (p less than 0.01). During the maintenance year, 15 patients (29%) given cimetidine at night relapsed. Addition of MMSC or cysteine to cimetidine incurred a significantly (p less than 0.001) lower relapse rate. During the year following maintenance therapy, the relapse rate in the group that had been previously treated with cimetidine alone (63%, n = 51) was significantly (p less than 0.001) higher than that in the groups previously treated with MMSC and cimetidine (6%, n = 67) or cysteine with cimetidine (6%, n = 64). The results suggest that sulphydryl containing agents stimulate the healing and protect against the recurrence of duodenal ulceration. PMID- 1438526 TI - Antitumor activity of siwenmycin: a novel anthracycline antibiotic. AB - A novel anthracycline antibiotic, siwenmycin, isolated from the culture of Streptomyces galilaeus var. siwenesis, was examined for its antitumor activities against P388, K562, B16-F10, HeLa, HEp-2 and Lewis lung carcinoma cell lines. The results showed that siwenmycin was effective against P388, K562, HeLa and HEp-2 tumor cell lines in vitro, and significantly inhibited the growth of the Lewis lung carcinoma cell line in vivo. Siwenmycin could also suppress spontaneous and artificial pulmonary metastases of B16-F10 and Lewis lung carcinoma cell lines in C57BL/6 mice. The inhibitory effect of siwenmycin on spontaneous pulmonary metastasis of Lewis lung carcinoma in C57BL/6 mice was even stronger than that of adriamycin (ADM), which is, at present, commonly used in clinical practice. Furthermore, the double-labeling test used in this study has verified that siwenmycin can inhibit cellular RNA synthesis at about one tenth the concentration required to inhibit DNA synthesis to the same degree, indicating that the antitumor mechanism of siwenmycin also differs from that of ADM. The acute toxicity of siwenmycin was very low, and it was as effective in vivo as in vitro, suggesting that this newly found antibiotic should be studied for possible clinical antitumor applications. PMID- 1438527 TI - Relationships between ondansetron systemic exposure and antiemetic efficacy and safety in cancer patients receiving cisplatin. AB - Single concentration estimators of systemic exposure to the serotonin type 3 receptor antagonist and antiemetic, ondansetron, were established in 55 cancer patients receiving cisplatin-based chemotherapy plus a daily regimen of ondansetron given every 4 h for 3 doses on each day of chemotherapy. Ondansetron plasma concentration measured 4 h after the first daily dose of ondansetron (C[4h]) proved to be a reliable index of AUC and hence of systemic exposure. In patients receiving dosages of cisplatin < 95 mg/m2, the risk of emesis was greatest among those with the lowest systemic exposure to ondansetron. Most patients (64%) experienced emesis if C[4h] was < 20 ng/ml, whereas emesis did not occur in any patient with C[4h] > 80 ng/ml. Among patients receiving very high dosages of cisplatin (> 95 mg/m2), comparable levels of systemic exposure were not totally effective in preventing emesis. For these patients, more ondansetron was required to block the greater emetic stimulus produced by higher doses of cisplatin. This difference reflects a shift in the log exposure versus response relationship, and is consistent with serotonin antagonism at a receptor. In contrast, reported side effects of ondansetron were not related to exposure. PMID- 1438528 TI - Comparison of the in vitro effects of K+ channel modulators on detrusor and portal vein strips from guinea pigs. AB - The effects of K+ channel openers and blockers on smooth muscles of vascular and nonvascular origin from guinea pigs have been investigated. Cromakalim, pinacidil, nicorandil and minoxidil sulfate all abolished the spontaneous myogenic activity of the guinea pig portal vein and the KCl-evoked activity of detrusor strips with the same rank order of ptoency. Whereas both apamin and charybdotoxin stimulated myogenic activity of the detrusor strips, they produced insignificant effects on spontaneously active portal vein strips and failed to antagonize the mechanoinhibitory effects of cromakalim in the two tissues. Glibenclamide, on the other hand, only stimulated the myogenic activity of portal vein strips but antagonized the mechanoinhibitory effects of cromakalim, pinacidil, nicorandil and minoxidil sulfate in both tissues. Rubidium, at millimolar concentrations, stimulated the myogenic activity, and antagonized the actions of cromakalim in both tissues. The data indicate that there are definite functional dissimilarities as exhibited by the differential response of the two tissues to K+ channel modulators. These findings may be exploited in the design of new drugs with tissue selectivity. PMID- 1438529 TI - Transport of cimetidine across the basolateral membrane of rabbit kidney proximal tubules: interaction with organic anions. AB - Since in whole animal studies and in man the renal clearance of cimetidine was prolonged by the coadministration of probenecid, the aim of the present study was to examine the interaction of the organic base cimetidine with the organic anion transport system at the basolateral membrane of isolated non-perfused rabbit proximal tubules. S2 segments of proximal tubules were incubated at 37.5 degrees C with 3H-cimetidine (2 x 10(-7) mol/l) or 3H-PAH (4 x 10(-6) mol/l, as a marker for the organic anion transport system) and 14C-inulin (marker for the extracellular space) for 25 min to achieve a steady state. Afterwards, a nonradiolabelled substance was added to the bath, and the change of the cellularly stored radioactivity was measured at 5-min intervals. Probenecid (5 x 10(-5) mol/l) decreased the cellular amount of 3H-cimetidine to 26% of the control value. At this concentration, furosemide and Na2SO4 had no effect. At a concentration of 10(-3) mol/l, these substances reduced the cellular 3H cimetidine uptake to 33% (furosemide) and 57% (Na2SO4) of the control value. 10( 4) and 10(-3) mol/l succinate diminished the steady-state uptake of cimetidine to 77% and 53% of the control value, respectively. On the other hand, cimetidine (10(-3) mol/l) decreased the cellular uptake of 3H-PAH to 52% of the control value. N1-methylnicotinamide (5 x 10(-5) mol/l and 10(-3)mol/l) had no effect on the steady-state uptake of 3H-PAH. These results indicate that the organic base cimetidine, besides its high affinity for the cation transporter, also interacts with the organic anion transport system at the basolateral membrane of rabbit proximal tubules. PMID- 1438530 TI - Endothelins and sarafotoxins: physiological regulation, receptor subtypes and transmembrane signaling. AB - The endothelins and sarafotoxins are two structurally related families of potent vasoactive peptides. Although the physiological functions of these peptides are not entirely clear, the endothelins are probably involved in pathophysiological conditions such as hypertension and heart failure. This review summarizes the state of the art in some areas of this intensively studied subject, including: (1) structure-function relationships of ET/SRTX, (2) ET concentrations in plasma, (3) ET/SRTX receptor subtypes and (4) signaling events mediated by the activation of ET/SRTX receptors. PMID- 1438531 TI - Aldose reductase inhibitors and diabetic complications. AB - Aldose reductase inhibitors impede flux of glucose through the sorbitol pathway in diabetes mellitus. They therefore reduce the accumulation of the pathway metabolites, sorbitol and fructose, reduce the impact of the flux on the cofactors used by the pathway and reduce other derived phenomena, such as osmotic stress and myo-inositol depletion. As drugs, their targets are the chronic complications of diabetes--neuropathy, retinopathy, nephropathy and vasculopathy. In experimental models there is proof of activity against biochemical, functional and structural defects in all of the involved tissues, but we await full clinical verification of this potential. PMID- 1438532 TI - Ornithine decarboxylase as an enzyme target for therapy. AB - Interest in ornithine decarboxylase (ODC) and the therapeutic effects of its inhibition with the consequent depletion of polyamine biosynthesis has been widespread since the late 1970s and 1980s. This review covers new information about the properties of ODC, recent findings with ODC inhibitors and a discussion of the mechanism of inactivation of ODC by eflornithine. Recent in vivo therapeutic approaches of ODC inhibition are also discussed including: cancer and cancer chemoprevention; autoimmune diseases; polyamines and the blood-brain barrier, ischemia and hyperplasia; the NMDA receptor and modulation by polyamines; hearing loss; African trypanosomiasis; Pneumocystis carinii pneumonia and Cryptosporidium in AIDS; and other infectious diseases/organisms. PMID- 1438533 TI - Mitochondrial DNA damage by anticancer agents. AB - Mitochondrial DNA (mtDNA) is susceptible to damage by a number of anticancer agents either directly or indirectly. This damage is of little consequence if only a few of the mtDNA molecules are damaged. However, multiple drug treatments could result in a significant effect on a cell's ability to survive. The differential effect of anticancer agents on either organ specific toxicities or selective tumor kill can be partially accounted for by differential mtDNA content of cells and on the basis of differential protective mechanisms within mitochondria of various organs or tumor tissue. The concept of damage to mitochondria, especially its genome, is a subject of active investigation in various laboratories. This area of research may provide mechanism(s) by which organ specific toxicities or tumor specific toxicities may be elaborated. Also, the concept of targeting tumor specific mitochondria and/or mtDNA by anticancer agents is very attractive but has not come to fruition due to a lack of understanding of the regulation of the genome in tumor cells. Future investigations in this arena will enhance our knowledge on the interaction between anticancer agents and extranuclear DNA. PMID- 1438534 TI - The shoteh: a discussion of the Jewish rabbinic view of insanity. PMID- 1438535 TI - Inborn basis for the healing doctor-patient relationship. PMID- 1438536 TI - Multidisciplinary madness: the trials and tribulations of the MD-PhD. PMID- 1438537 TI - Ms. Thompson's murmur. PMID- 1438538 TI - Hans Zinsser: as I remember him. PMID- 1438539 TI - Mentors and role models. PMID- 1438540 TI - Of fire and ash. PMID- 1438541 TI - Teaching internal medicine. PMID- 1438543 TI - Situation ethics. PMID- 1438542 TI - Teaching internal medicine. PMID- 1438544 TI - Teaching internal medicine. PMID- 1438545 TI - About Europa Europa. PMID- 1438546 TI - About Europa Europa. PMID- 1438547 TI - Past and present. Alice Freeman Palmer, nineteenth-century feminist. PMID- 1438548 TI - "Lies, damn lies, and statistics" in clinical research. PMID- 1438549 TI - Feasibility study of an electret dosimetry technique. AB - Characteristics of a radiation charged electret dosimeter are described. The dosimeter is based on a parallel-plate ionization chamber with the exception that the collecting electrode is covered by a thin polymer, Teflon or Mylar. During the charging of the dosimeter, ions produced in the sensitive volume by an external radiation source drift in the externally applied electric field and become trapped on the polymer surface forming an electret. Once the external supply is removed, a field across the sensitive volume is produced by the electret charge, such that during any subsequent irradiation, ions opposite in sign to those on the electret surface are attracted to the electret and deplete the charge layer in an amount proportional to the air kerma. The remaining charge on the electret is read by an electrometer, through further irradiation. This technique allows the dosimeter to be simultaneously charged and calibrated, used in the field, simultaneously discharged and read, and reused again in situ without dismantling the dosimeter. Various parameters, however, were considered by direct discharge, rather than by initial exposure and subsequent measurement. Calibration, energy dependence, air kerma range, and reproducibility are discussed, and guard-ring effects on the linearity of the chamber are presented. Measurements of natural charge decay on the electrets are introduced. PMID- 1438550 TI - Optimization of the electric field distribution in a large volume tissue equivalent proportional counter. AB - Large volume tissue-equivalent proportional counters are of interest in radiation protection metrology, as the sensitivity in terms of counts per unit absorbed dose in these devices increases as the square of the counter diameter. Conventional solutions to the problem of maintaining a uniform electric field within a counter result in sensitive volume to total volume ratios which are unacceptably low when counter dimensions of the order of 15 cm diameter are considered and when overall compactness is an important design criterion. This work describes the design and optimization of an arrangement of field discs set at different potentials which enable sensitive volume to total volume ratios to approach unity. The method has been used to construct a 12.7 cm diameter right cylindrical tissue-equivalent proportional counter in which the sensitive volume accounts for over 95% of the total device volume and the gas gain uniformity is maintained to within 3% along the entire length of the anode wire. PMID- 1438551 TI - Precision of mean transit time measurements in 99Tcm-DTPA renal scintigraphy: a Monte Carlo study. AB - The precision of renal mean transit time (MTT) measurements by 99Tcm-DTPA scintigraphy was studied by a Monte Carlo procedure. Data were obtained from twenty mild essential hypertensives with normal renal function. An ensemble of equivalent data sequences was constructed for each renal time-activity curve (TAC), assuming the dominant noise in the data to be Poisson in character. TACS were deconvolved by the matrix method and MTT was inferred from retention functions by a procedure entailing a nonlinear least-squares minimization. For every ensemble of data sequences a distribution of MTTs was generated. The population-averaged coefficients of variation for these distributions were 1.6% and 2.6%, for whole-kidney and cortical data, respectively. We conclude that the precision of MTT determination from clinical data is comparable to that from simulated data. MTT measurements may be useful for detecting functional changes in individual kidneys following an intervention such as angiotensin-converting enzyme inhibition. PMID- 1438552 TI - Dose rate distributions around 60Co, 137Cs, 198Au, 192Ir, 241Am, 125I (models 6702 and 6711) brachytherapy sources and the nuclide 99Tcm. AB - Simple analytical functions derived from our point source Monte Carlo calculations on the combined attenuation and scatter factor, B exp(-mu r), for 60Co, 137Cs, 198Au, 192Ir, 241Am, 125I (models 6702 and 6711) brachytherapy sources and the nuclide 99Tcm, for water spherical geometries of radii R = 15 and 20 cm, are presented. Our results for the broadly used 60Co, 137Cs, 198Au and 192Ir brachytherapy sources can be compared directly and found in excellent agreement with the widely accepted data of Meisberger et al in the limited distance range for which the latter are valid. Our data, however, can be used with high accuracy outside this distance range. Many discrepancies observed among different data sets available in recent literature are attributable to differences in geometries used. The results for the recently introduced 241Am source are very dissimilar to those produced by any other currently used brachytherapy source. Dose rate distributions, based on the above simple functions, are proposed in accordance with the recommendations for calibration of the brachytherapy sources in terms of reference air kerma rate and were found to be in good agreement with data available in the literature. Our calculations for 125I sources (models 6702 and 6711), provided that the characteristic x-rays from titanium encapsulation are taken into account, support recent experimental and theoretical dose rate distributions indicating that currently accepted values for 125I may be overestimated. PMID- 1438553 TI - Photon absorption measurements of bone density in the presence of scattered radiation. AB - Bone density measurements are frequently carried out using photon absorptiometry techniques. The analysis of data collected in this way depends upon scatter-free detector signals. In practice the detector and source collimation lead to high levels of scattered radiation being detected. An analysis of the problem using photon transport computer models has shown that the current systems are reasonably insensitive to the scatter contribution except where patient changes occur over a long series of measurements or where new results taken with DEXA are compared with those taken on older systems such as DPA. This is frequently the case since the major body of data related to serial bone density measurements has been achieved with DPA. Inclusion of scattered radiation in the bone density calculations can lead to a 0.5-3.5% reduction between system types. Patient size changes could lead to a reduction in bone density of 0.5% (femoral neck measurement) to 1% (lumbar spine measurement). PMID- 1438554 TI - Water-equivalent plastic scintillation detectors for high-energy beam dosimetry: I. Physical characteristics and theoretical consideration. AB - A minimally perturbing plastic scintillation detector has been developed for the dosimetry of high-energy beams in radiotherapy. The detector system consists of two identical parallel sets of radiation-resistant optical fibre bundles, each connected to independent photomultiplier tubes (PMTs). One fibre bundle is connected to a miniature water equivalent plastic scintillator and so scintillation as well as Cerenkov light generated in the fibres is detected at its PMT. The other 'background' bundle is not connected to the scintillator and so only Cerenkov light is detected by its PMT. The background signal is subtracted to yield only the signal from the scintillator. The water-equivalence of plastic scintillation detectors is studied for photon and electron beams in the radiotherapy range. Application of Burlin cavity theory shows that the energy dependence of such detectors is expected to be better than the commonly used systems (ionization chambers, LiF thermoluminescent dosimeters, film and Si diodes). It is also shown that they are not affected by temperature variations and exhibit much less radiation damage than either photon or electron diode detectors. PMID- 1438555 TI - Water-equivalent plastic scintillation detectors for high-energy beam dosimetry: II. Properties and measurements. AB - The properties of a new scintillation detector system for use in dosimetry of high-energy beams in radiotherapy have been measured. The most important properties of these detectors are their hgh spatial resolution and their nearly water-equivalence. Measurements have shown that they have excellent reproducibility and stability, and a linear response versus dose-rate. It is also shown that they have better spatial resolution than ionization chambers and have much less energy or depth dependence in electron fields due to the removal of the influence of the polarization effect. Dose distributions in water, using miniature plastic scintillation detectors, have been measured for different high energy photon and electron beams. PMID- 1438556 TI - The mass angular scattering power method for determining the kinetic energies of clinical electron beams. AB - A method for determining the kinetic energy of clinical electron beams is described. The method is based on the measurement in air of the spatial spread of a pencil electron beam which is produced from the broad clinical electron beam. As predicted by the Fermi-Eyges theory, the dose distribution measured in air on a plane, perpendicular to the incident direction of the initial pencil electron beam, is Gaussian. The square of its spatial spread is related to the mass angular scattering power which in turn is related to the kinetic energy of the electron beam. The measured spatial spread may thus be used to determine the mass angular scattering power, which is then used to determine the kinetic energy of the electron beam from the known relationship between mass angular scattering power and kinetic energy. Energies obtained with the mass angular scattering power method agree with those obtained with the electron range method. The angular scattering power method is relatively cumbersome, but allows us to determine the kinetic energies of electron beams from first principles, in contrast to the empirical methods based on range measurements in water. PMID- 1438557 TI - Tissue maximum ratios (and other parameters) of small circular 4, 6, 10, 15 and 24 MV x-ray beams for radiosurgery. AB - Small, circular, x-ray beams are commonly used for radiosurgery applications. Dosimetric characteristics of 4, 6, 10, 15 and 24 MV circular x-ray beams ranging in size from 10 to 40 mm are reported. These characteristics include the measurement of TMR, beam profiles and relative output factors. Measurements of these parameters were performed in a solid water phantom using film, a small diode, small parallel-plate and cylindrical ionization chambers and TLD. Comparison of relative dose measurements of small, circular beams performed using these detectors showed that the small diode, film and TLD results consistently agreed for circular beams as small as 10 mm diameter. Beam profiles were measured using film dosimetry. Comparison of TMR values of a 10 mm diameter beam measured using film and a small parallel-plate ionization chamber showed no significant differences. Tertiary collimators designed with tapered, divergence-matching holes, and straight-drilled holes have been used for radiosurgery applications. Measurement of beam penumbra produced with either of these types of tertiary collimators showed minimal differences between them. PMID- 1438558 TI - A megavoltage CT scanner for radiotherapy verification. AB - We have further developed a system for generating megavoltage CT images immediately prior to the administration of external beam radiotherapy. The detector is based on the scanner of Simpson (Simpson et al 1982)--the major differences being a significant reduction in dose required for image formation, faster image formation and greater convenience of use in the clinical setting. Attention has been paid to the problem of ring artefacts in the images. Specifically, a Fourier-space filter has been applied to the sinogram data. After suitable detector calibration, it has been shown that the device operates close to its theoretical specification of 3 mm spatial resolution and a few percent contrast resolution. Ring artefacts continue to be a major source of image degradation. A number of clinical images have been presented. The next stage of this work is to use the system to make clinical measurements of patient set-up inaccuracies building on our work making such measurements from digital portal images (Evans et al 1992). PMID- 1438559 TI - Comments on phantoms for hyperthermia and impedance tomography. PMID- 1438560 TI - Ultrasound scattering from spherical tumours. AB - The interaction of biomedical ultrasound with spherical tumours in the human body is investigated using analytic methods which predict the angular distribution of the ultrasound scattered by the tumour. Both the tumour and the surrounding tissue are considered to be lossy elastic media, which support shear-wave modes in addition to the familiar compressional-wave acoustic modes. Exact expressions for the angular distribution of the ultrasonic energy scattered by the tumour are used to illustrate graphically the behaviour of plane ultrasound wave interactions. PMID- 1438561 TI - The dielectric parameters of excised EMT-6 tumours and their change during hyperthermia. AB - The electrical impedance from 100 Hz to 40 MHz of freshly excised EMT-6 tumours was measured periodically while the tumours were exposed to typical hyperthermia heating regimens. During hyperthermia, the EMT-6 tumour displays a characteristic response sequence which includes cellular swelling, progressive membrane damage, cellular shrinking and subsequent progressive histolysis. It was found that the changes in the tumour tissue dielectric properties reflected these hyperthermia induced histological changes. In particular the parameters delta epsilon, sigma s and fc progressed to, reached, and retreated from extrema as the cells swelled to a maximum and then contracted. These parameters continued retreating beyond their original values as the beta-dispersion progressively collapsed during the period of progressive histolysis. The Cole-Cole parameter alpha increased during most of these histological changes, indicating a broadening of the dispersion, which suggests differential cell response during this period. Differences in the time course between dielectric components may reflect the combined effects of cellular swelling and concurrent progressive membrane changes. Changes in rate and shape of the dielectric response with hyperthermia temperature are discussed in terms of possible cellular responses during hyperthermia. PMID- 1438562 TI - Calculation of body transport function. AB - A new model for simulation of recirculation has been developed which describes the measured concentration-time course of a drug in the aorta. It is based on repetitive convolution of the injected input dilution curve with a body transport function plus the input dilution curve. If the basic shape of a body transport function, i.e. such as log-normal distribution, is known, it is possible to calculate the parameters of this function with a non-linear least-squares procedure from measured tracer dilution data. In the present investigation this algorithm is used to estimate the body transport function for experimental data, obtained in two experiments with sheep. Once the body transport function is known, the formula can be used to describe the dispersion of a drug. Intravascular concentration time curves at different places in the body can also be predicted or the blood volume can be estimated. PMID- 1438563 TI - Conversion of ionization measurements to radiation absorbed dose in non-water density material. AB - The radiation absorbed dose to non-water equivalent materials of interest in radiotherapy is the dose to lung and the dose to bone. The measurement and calculation of dose to the lung has been of great interest and much effort has gone into the development of accurate lung dose calculation methods. The radiation absorbed dose to the bone is usually not calculated and most absorbed dose calculations have been done without correcting for the presence of bone. For the lower megavoltage photon beams this may be appropriate, however, as the energy of the photon beam increases, the region of electronic disequilibrium becomes larger and pair production which depends on the atomic number of the material becomes significant. Therefore the bone will produce greater perturbations of the dose distribution. The dose to lung-equivalent material is uniquely obtained from ionization measurements. However, in bone-equivalent materials two different calculations of absorbed dose are possible: the absorbed dose to soft tissue plastic (polystyrene) within bone-equivalent material and the dose to the bone-equivalent material itself. Both can be calculated from ionization measurements in phantoms. These two calculations result in significantly different doses in a heterogeneous phantom composed of polystyrene and aluminium (a bone substitute). The dose to a thin slab of polystyrene in aluminium is much higher than the dose to the aluminium itself at the same depth in the aluminium. Monte Carlo calculations confirm that the calculation of dose to polystyrene in aluminium can be accurately carried out using existing dosimetry protocols. However, the conversion of ionization measurements to absorbed dose to high atomic number materials cannot be accurately carried out with existing protocols and appropriate conversion factors need to be determined. PMID- 1438564 TI - Estimation of effective dose to the patient during medical x-ray examinations from measurements of the dose-area product. AB - Effective dose is likely to be used as a dose index for patient exposures in diagnostic radiology. Calculation of effective dose requires estimates of doses to many organs. In the absence of such dose data it would be useful to be able to directly estimate effective dose from a quantity that can be easily measured in the x-ray room. Relationships between effective dose and each of entrance surface dose, entrance air kerma and dose-area product were studied for common radiographic projections using the organ dose data from Monte Carlo modelling performed at the National Radiological Protection Board, UK. Dose-area product proved to be the best quantity for estimating effective dose and these data are presented. For typical peak generating potentials, estimates of effective dose can be made from dose-area product using a small number of conversion coefficients. For cervical spine, chest, kidneys, abdomen, lumbar spine and pelvis AP projections, the conversion coefficient 0.21 mSv per Gy cm2 will estimate effective dose within 30% of the value obtained using specific organ doses. Conversion coefficients for lateral and PA projections of the trunk are approximately half this value. These coefficients allow the direct estimation of effective dose with sufficient accuracy for most purposes. PMID- 1438565 TI - Flavin-sensitized photochemically induced dynamic nuclear polarization detection of pyrimidine dimer radicals. AB - A photochemically induced dynamic nuclear polarization (photo-CIDNP) study of carboxymethyllumiflavin-sensitized splitting of pyrimidine dimers has been carried out. In aqueous solution at high pH, an emission signal (delta 3.9 ppm) was observed from the dimer C(6)- and C(6')-protons of an N(1), N(1') trimethylene-bridged thymine dimer (1). The dimer photo-CIDNP signal was seen only above pD 11.6 and was most intense at pD 12.9. Also observed were weak enhanced absorption signals from the product of splitting, trimethylenebis(thymine) (delta 1.7 and 7.2 ppm). In contrast, cis, syn-thymine dimer (3) gave no photo-CIDNP signals from the dimer. An enhanced absorption at 1.8 ppm, however, due to the product of splitting (thymine) was observed. It was found that dimer 1 and, to a lesser extent, dimer 3 quenched flavin fluorescence. An N(3),N(3')-dimethylated derivative of 1, however, failed to quench flavin fluorescence. Comparison of the pD profile of the dimer photo-CIDNP signal to the pKa values for thymidine dimer suggested that principally the dideprotonated dimer undergoes electron abstraction by the excited flavin. PMID- 1438566 TI - Photophysical property of sanguinarine in the excited singlet state. AB - The photophysical property of the alkanolamine form of sanguinarine has been studied in aqueous and organic medium under various environmental conditions from the measurement of absorption, fluorescence and NMR spectroscopy. Alkanolamine fluorescence shows an excitation time dependent fluorescence quenching and the rate of quenching increases significantly with increasing pH and concentration of the species, while it decreases with increasing temperature. This phenomenon is explained by excited state intramolecular proton transfer from a 6-OH group to the lone pair of nitrogen through the formation of zwitterion. PMID- 1438567 TI - Laser mediated release of dye from liposomes. AB - Liposomes made from phospholipids and containing sulforhodamine dye (1-50 mM) have been irradiated with nanosecond and picosecond laser pulses. Individual liposomes were locally heated by laser absorption of dye dimers during a single laser pulse, and heating was sufficient to release the liposome contents. The extent of dye release produced by a single laser pulse was shown to be quantitatively dependent on several interdependent variables, including dye concentration, liposome size, laser excitation parameters and initial temperature of the dye-liposome system. Fluorescence lifetime data having three components have been obtained and analyzed in terms of three dye environments. Quantitative estimates support a photo-induced thermal mechanism for liposome lysis and release of its contents. These results may be useful for laser induced delivery of therapeutic agents or other applications of lasers in biological systems. PMID- 1438568 TI - Mitotic inhibition by phenylporphines and tetrasulfonated aluminium phthalocyanine in combination with light. AB - This work relates to studies on modes of phototoxicity by tetrasulfonated aluminium phthalocyanine (AlPcS4), tetrahydroxy- and monosulfonated meso tetraphenylporphines (3-THPP and TPPS1) on culture cells. Toxicity at moderate light exposures appears to be related to inhibition of microtubule function. Treatment of human cervix carcinoma cells of the line NHIK 3025 incubated for 18 h with the sensitizers and exposed to light inhibits multiplication for the first hours after light exposure, a significant fraction of the cells accumulating in mitosis. For the first hours after treatment, the mitotic cells were always mainly found in metaphase; generally seen as c-metaphases and three-group metaphases. During this time, anaphase and telophase cells were absent or greatly reduced in number. Indirect immunofluorescence staining of beta-tubulin showed that the spindle apparatus of mitotic cells was perturbed in all cases. The accumulation in mitosis was more extensive after treatment with AlPcS4 and light than after treatment with 3-THPP or TPPS1 and light. This may be related to the great difference in the lipophilic properties of these sensitizers; i.e. AlPcS4 being highly water soluble while TPPS1 and 3-THPP are lipophilic sensitizers. The lipophilicity of several sensitizers has been measured by two different methods, the partition between an aqueous and a lipophilic phase (Triton X-114) and the binding strength to a reverse phase column. The results show that the measured relative lipophilicity of the sensitizers may be influenced by the method of analysis. PMID- 1438569 TI - The phototoxicity of 8-methoxythionepsoralen and 6-methylthionecoumarin. AB - The phototoxicity of 8-methoxythionepsoralen (8-MOTP) and 6-methylthione coumarin (6-MTC) when activated by UV-A has been investigated using a variety of Escherichia coli strains, Haemophilus influenzae transforming DNA and Escherichia coli pBR322 plasmid DNA. The results demonstrate that 8-MOTP is a strictly oxygen independent photosensitizer that is about 500-fold less efficient in forming lesions leading to equivalent lethality than is the parent compound from which it is derived (8-MOP). As is true for 8-MOP, 8-MOTP is capable of inducing histidine independent mutations in E. coli and inactivating transforming DNA consistent with DNA being a target for lesions induced by this molecule in the presence of UV-A. 6-MTC is a strongly oxygen dependent photosensitizer activated by UV-A when tested with either E. coli cells or transforming DNA in contrast to the parent compound (6-methylcoumarin; 6-MC) which is not phototoxic when treated with UV-A. These results imply that the membrane may be an important target leading to lethality. 6-MTC in the presence of UV-A can inactivate pBR322 plasmid and Haemophilus influenzae transforming DNA activity in vitro suggesting that DNA is a potential target for this molecule when activated by UV-A. PMID- 1438570 TI - Potentiation of oxidative damage to proteins by ultraviolet-A and protection by antioxidants. AB - We have studied the damage of alcohol dehydrogenase (ADH) and glyceraldehyde 3 phosphate dehydrogenase (GAPD) induced by Fe++/EDTA + H2O2 in combination with UV A (main output at 365 nm). Enzyme inactivation, formation of hydroxyl radicals (measured in the absence of enzymes), increase in protein carbonyls, oxidation of sulfhydryl (SH) groups, loss of native protein fluorescence, and enhanced protease degradation were used to determine protein damage. Hydroxyl radical production was greatly enhanced by the combination of UV-A with Fe++/EDTA + H2O2. The combined treatment increased protein carbonyls but decreased native protein fluorescence and SH groups. The combined treatment caused turbidity in GAPD but not in ADH, whereas trypsin susceptibility was increased more in ADH than in GAPD. These measurements of protein oxidation correlated well with enzyme activities. Glyceraldehyde 3-phosphate dehydrogenase and dithiothreitol were most protective against such damage, while hydroxyl radical and singlet oxygen scavengers were partially effective. Superoxide dismutase had no effect. Thus, UV A potentiation of protein damage induced by FE++/EDTA + H2O2 appeared to involve hydroxyl radicals and perhaps singlet oxygen but not superoxide radicals. The damage to proteins induced by combination of UV-A with physiological oxidants, iron ions and H2O2 may be relevant to UV-A-induced skin and tissue damage. PMID- 1438571 TI - Repair of thymine dimers and (6-4) photoproducts in group A xeroderma pigmentosum cell lines harboring a transferred normal chromosome 9. AB - Transfer of a normal chromosome 9 into a xeroderma pigmentosum (XP)-A cell line partially restored its DNA repair activity. XP-A cell lines harboring a transferred chromosome were much more UV-resistant than parental XP-A cells but still more UV-sensitive than normal cells. The amount of UV-induced unscheduled DNA synthesis was only one-third of that in normal cells. The repair of thymine dimers and (6-4) photoproducts in these cell lines was analyzed by using monoclonal antibodies raised against them. Although these XP-A cell lines carrying a normal chromosome 9 could repair (6-4) photoproduct with a little lower efficiency than normal cells, the repair of thymine dimers was completely absent in these cells. The present results suggest a gene-dosage effect in DNA excision repair mechanisms in human cells or a rather complicated mechanism which involves two or more pathways. PMID- 1438572 TI - Base release from DNA and polynucleotides upon 193 nm laser excitation. AB - Release of bases form calf thymus DNA and three polynucleotides, induced by 20 ns excitation at 193 nm in aqueous solution at pH 7, was detected by HPLC. The quantum yields of formation of free bases (phi B) from double-stranded DNA (0.4 mM) are independent of intensity, indicating a one-quantum mechanism of N glycosidic bond cleavage. The phi B values increase in the order guanine, thymine, adenine, cytosine, the latter being phi C approximately 7 x 10(-4) for double-stranded DNA under Ar and O2. The larger phi B values in N2O-saturated solution, e.g., phi C = 1.2 x 10(-3), are ascribed to additional base release via OH-adduct radicals. The phi B values of homopolynucleotides increase in the order poly(G), poly(A) and poly(C), e.g. phi C = 7 x 10(-3) under Ar, as do the efficiencies for base release per radical cation (eta B). A comparison of the eta B values with the efficiencies of single-strand breakage for poly(C), poly(A) and DNA shows a similar trend; both are markedly larger for pyrimidines than for purines. Pathways to undamaged bases, initiated from base radical cations, are proposed. PMID- 1438573 TI - Effects of light beam size on fluence distribution and depth of necrosis in superficially applied photodynamic therapy of normal rat brain. AB - The light fluence distributions of 632.8 nm light incident on the exposed surface of normal rat brain in vivo have been measured using an interstitial, stereotactically-mounted optical fiber detector with isotropic response. The dependence of the relative fluence rate on depth and the spatial distribution of fluence were compared for incident beam diameters of 3 and 5 mm. The fluence rate at depth of 1-6 mm along the optical axis within the brain tissue was approximately 70% greater for a 5 mm diameter beam than for a 3 mm beam, at the same incident fluence rate, although the plots of the relative fluence rate vs depth were parallel over the depth range 1-6 mm. The depths of necrosis resulting from photodynamic treatment of brain tissue using the photosensitizer Photofrin and irradiation by 632 nm light with 3 and 5 mm incident beams were also measured. The observed difference in necrosis depths was consistent with the measured difference in fluence. The importance of beam size in photodynamic treatment with small diameter incident light fields is discussed. PMID- 1438574 TI - Improved survival from intracavitary photodynamic therapy of rat glioma. AB - The effectiveness of intratumoral photoradiation in photodynamic therapy (PDT) using a polyporphyrin photosensitizer was studied in the RT-2 rat glioma model. One week after intracerebral implantation of RT-2 cells, experimental rats received a single i.p. injection of 2 mg/kg of Photofrin. After administration of the photosensitizer (48 h), the tumors were partially resected and the exposed cavity was irradiated with 15 J of laser light at a wavelength of 630 nm. Further treatment with a large craniectomy significantly enhanced rat survival. Control rats which received no photosensitizer but were treated with surgery, alone or in combination with laser irradiation, succumbed from early tumor recurrence. Photodynamic therapy without decompressive surgery resulted in hemorrhagic infarction of residual tumor and adjacent brain with focal cerebral edema which resulted in cerebral herniation and early death. Our results indicate that photodynamic therapy is effective in treating residual brain tumor but at the expense of brain tissue surrounding the tumor. Unless relieved, intracranial pressure from photodynamic therapy-associated cerebral edema in this animal model resulted in shortened survival. PMID- 1438575 TI - Cellular delivery and retention of photofrin: II. The effects of human versus mouse and bovine serum. AB - The effects of human serum (HS), mouse serum (MS) and fetal bovine serum (FBS) on cellular delivery and retention of Photofrin were examined using human lung tumor cells (A549) cultured in vitro. The results show that these three kinds of sera exhibit substantial differences in: (i) degree of inhibition of Photofrin cellular uptake, (ii) retention capacity of Photofrin delivered to the cells in their presence and (iii) efficacy of promoting the clearance of Photofrin from the cells. It is suggested that these differences originate from unequal interaction of each of the sera with Photofrin material, which in turn is the consequence of variability in composition and in the levels of serum proteins in HS, MS and FBS. The highest degree of Photofrin disaggregation and and competitive binding of its constituents was attributed to HS. The lowest degree of Photofrin disaggregation, and the competitive binding limited mostly to monomeric porphyrin forms was implicated for FBS. For MS, the spectroscopic and cellular data indicated a lesser degree of Photofrin disaggregation than with HS, with little if any consequence in Photofrin retention characteristics. The implication of this comparative analysis is that in vitro studies using FBS may underestimate the extent of interaction of Photofrin with serum proteins in humans, and overestimate the retention capacity of the photosensitizer in human tissues. Studies in vivo using a mouse model may also underestimate the degree of disaggregation of Photofrin in human circulation, and give different photosensitizer tissue retention levels than in humans. PMID- 1438576 TI - Singlet oxygen quantum yield of sulfur and selenium analogs of psoralen. AB - The quantum yield of singlet oxygen production by eight newly synthesized sulfur and selenium analogs of psoralen irradiated with UV-A (366 nm) has been determined in CCl4 with the help of the steady state luminescence technique. The new psoralen derivatives are generally better singlet oxygen producers than psoralen itself. In particular, the replacement of selenophene for furan and/or of thiopyrone for pyrone induces an important enhancement of the singlet oxygen quantum yield. PMID- 1438577 TI - Dihydroxy-carotenoid liposomes inhibit phototoxicity in Paramecium caudatum. AB - The phototoxic effects of hematoporphyrin derivative, using Paramecium caudatum as a model system, are significantly reduced in the presence of carotenoid containing liposomes. Multilammelar large or small unilammelar vesicles, containing specific carotenoids, were effective in protecting the organism, whether administered exogenously in the bathing solution, or via incubation of paramecia in starved culture media containing carotenoid liposomes. The effectiveness of the carotenoids as inhibitors of phototoxic effects was found to depend on the mode of administration, with small unilammelar being more effective than multilammelar large vesicles for all carotenoids tested. Small unilammelar vesicles containing the dihydroxy-carotenoids zeaxanthin or astaxanthin afforded the greatest protection in both exogenous and endogenous studies. The results of this study suggest that carotenoid efficacy may be determined, in part, by the environment of the carotenoid molecules. PMID- 1438578 TI - Pathways of glycogen repletion. PMID- 1438579 TI - Mammalian stress response: cell physiology, structure/function of stress proteins, and implications for medicine and disease. PMID- 1438580 TI - Molecular and cellular basis of immune protection of mucosal surfaces. PMID- 1438581 TI - Fatty acid homeostasis in the normoxic and ischemic heart. PMID- 1438582 TI - Blood oxygen transport in the early avian embryo. PMID- 1438583 TI - Role of the cerebellum in visual guidance of movement. PMID- 1438584 TI - A time integral of membrane currents. PMID- 1438585 TI - Matching dendritic neuron models to experimental data. PMID- 1438586 TI - Voltage-dependent potassium channels since Hodgkin and Huxley. PMID- 1438587 TI - Molecular biology of voltage-dependent potassium channels. PMID- 1438588 TI - Metabolism of garlic constituents in the isolated perfused rat liver. AB - The metabolic and kinetic behaviour of different garlic (Allium sativum L., Alliaceae) constituents were investigated in the isolated perfused rat liver, using aqueous extracts of garlic powder as well as isolated allicin, the main product of the enzymatic degradation of alliin. Allicin (allyl thiosulfinate) showed a remarkable first pass effect and passed the liver unmetabolized only at high concentrations which caused considerable cell injuries. Diallyl disulfide and allyl mercaptan were identified as metabolites of allicin, whereby diallyl disulfide probably is the metabolic precursor of allyl mercaptan as shown by perfusion with diallyl disulfide alone. The metabolites diallyl disulfide and allyl mercaptan could be determined in the perfusion medium as well as in the bile and the liver tissue. Other degradation products of garlic were also investigated in this model. Ajoenes and vinyldithiins were detected in perfusion medium after liver passage but no metabolites of them could be identified up to now. PMID- 1438589 TI - Effects of Calaguala and an active principle, adenosine, on platelet activating factor. AB - Calaguala, an extract from the fern Polypodium decumanum, has been used to treat psoriasis and related immunological disorders. In an effort to explain Calaguala's medicinal effects the inhibitory activity of the extract in two platelet activating factor (PAF) related models has been investigated. In the first model, PAF was used to induce release of the proteolytic enzyme elastase in human neutrophils. Calaguala inhibited this effect with an IC50 of 0.1 mg/ml. The known PAF antagonist ginkgolide BN 52021 was used as a positive control and had an IC50 of 0.034 mg/ml. In the second model the inhibition of biosynthesis of PAF in neutrophils using lyso-PAF and labeled acetyl-CoA was studied. Also in this assay Calaguala showed a dose-dependent activity, the IC50 being 0.2 mg/ml. Since recent findings have indicated that PAF might be involved in the pathogenesis of psoriasis, it is possible that the activity shown by Calaguala in these PAF assays may contribute to the clinical efficacy of the extract. The PAF induced exocytosis assay was further used to guide the fractionation of the crude extract. From the acetone supernatant the nucleoside adenosine was isolated as an active principle. Pure adenosine dose-dependently inhibited the exocytosis induced by PAF (IC50 = 0.024 micrograms/ml) but was inactive in the biosynthesis assay. Adenosine is most probably one of the bioactive compounds of Calaguala responsible for its therapeutic properties. PMID- 1438590 TI - Effects of genistein, an isoflavone isolated from Genista tridentata, on isolated guinea-pig ileum and guinea-pig ileal myenteric plexus. AB - The inhibitory action of the major constituent of Genista tridentata L. (Papilionaceae), 4',5,7-trihydroxyisoflavone (genistein), on contractions induced by agonists and electrical field stimulation of smooth muscle was analysed. Genistein inhibited twitches evoked by electrical-stimulation of strips of guinea pig ileum with an IC50 value of 34 microM. Genistein (34 microM) inhibited contractions of the guinea-pig ileum by several agonists in a non-selective, antispasmodic action and had no effect on inhibition of 3H-ACh release from ileal myenteric plexus. Genistein (34 microM) produces an increase in cAMP levels of guinea-pig ileum which resulted in a smooth muscle relaxation which leads us to think that there must be a blockade of its phosphodiesterase. PMID- 1438591 TI - Antisickling activity of hydroxybenzoic acids in Cajanus cajan. AB - The amounts of phenylalanine and hydroxybenzoic acid in a Cajanus cajan methanolic extract were estimated. Results showed that the amount of phenylalanine and hydroxybenzoic acid per gram weight of bean was 4.92 mg +/- 0.13 mg and 21.0 mg +/- 3.0 micrograms, respectively. Sickling inhibition was observed to be efficient with the extract which contains a mixture of phenylalanine (0.69 mg/ml) and p-hydroxybenzoic acid (10.5 micrograms/ml), equivalent to those found in bean extract. The additive antisickling effect of both compounds can be therapeutically exploited for the treatment of sickle cell anemia. PMID- 1438592 TI - Activation of PC12 cells by lipophilic components of Panax ginseng. AB - The lipid soluble fraction of Panax ginseng C. A. Meyer has been found to possess a stimulatory effect on a para-neuronal culture cell line, namely PC12 cells. Addition of the diethyl ether extract (0.025-0.1 mg/ml) of Ginseng radix to a culture medium promoted the outgrowth of neurites from cells dose-dependently as well as their ready differentiation to respond to carbachol and high KCl-evoked membrane depolarization to induce free Ca2+ accumulation in the cells within a week of culture. Effective constituents of the extract were confined to four major substances detected in the extremely lipophilic front area on silica gel TLC. PMID- 1438593 TI - The molluscicidal activity of coumarins from Ethulia conyzoides and of dicumarol. AB - The molluscicidal principles of Ethulia conyzoides were identified as ethuliacoumarin A (1) and isoethuliacoumarin A (2). Ethuliacoumarin A possessed an LC90 between 19 and 23.5 ppm depending on the age of the snail against Biomphalaria glabrata, and between 12 and 15 ppm against Bulinus truncatus. In addition, ethuliacoumarin A was found to be cercaricidal at 25 ppm and ovicidal. Ethuliacoumarin has the structural requirements considered essential for anticoagulant activity. Consequently the anticoagulant dicumarol (4) was tested and found to be molluscicidal in the range from 2.5 to 10 ppm. In contrast, the coumarin anticoagulant warfarin (3) did not show molluscicidal activity. PMID- 1438594 TI - Anethofuran, carvone, and limonene: potential cancer chemopreventive agents from dill weed oil and caraway oil. AB - Bioassay-directed fractionation of dill weed oil and caraway oil, respectively, from the plants Anethum graveolens L. and Carum carvi L. (Umbelliferae) has led to the isolation of three monoterpenes, anethofuran (1), carvone (2), and limonene (3). Their structures were determined on the basis of spectral analysis. These compounds induced the detoxifying enzyme glutathione S-transferase in several mouse target tissues. The alpha,beta-unsaturated ketone system in carvone appeared to be critical for the high enzyme-inducing activity. PMID- 1438595 TI - Analysis and stability of Hyperici oleum. AB - Hyperici Oleum (St. John's wort oil) used in wound healing contains no hypericin. By using the sunlight maceration method described in the supplement to DAB 6 (EB 6), lipophilic breakdown products of this compound are obtained which lend the oil its red colour. Hyperforin, which is responsible for the oil's therapeutic activity could, for the first time, be identified and quantitatively determined by TLC and HPLC after solid-phase extraction. The stability of hyperforin is limited; sufficient shelf-life could only be achieved by hot maceration of dried flowers with eutanol G and storage in the absence of air. By gradient HPLC further polar hyperforin analogues were detected in those St. John's wort oils in which hyperforin had decomposed. At the same time flavonoids and xanthones could be identified. A procedure for the quantitative determination of flavonoids in St. John's wort was validated. The action of light during preparation of the oil led to a rise in the content of flavonoids. PMID- 1438596 TI - Free amino acids and toxins in Lathyrus sativus seedlings. PMID- 1438597 TI - [Phenomenological study of the visual perception metamorphosis in schizophrenia]. PMID- 1438598 TI - [Neurotic symptoms of borderline patients: a case review study]. AB - The author investigated neurotic symptoms of borderline patients by reviewing the clinical charts of twenty-six patients of longer than one year treatment period (8 men, 18 women; 23 patients with DSM III-R borderline personality disorder (BPD), 14 with schizotypal personality disorder (SPD), (11 BPD-SPD overlaps); age at the first contact: mean = 24.3 y. o., SD = 6.7 y. o.; treatment period: mean = 51 months, SD = 35 months). The diagnoses of the comorbid neurotic disorders were obsessive compulsive disorder: 5 cases (19% (BPD: 22%, SPD: 7%)), somatoform disorder: 5 (19% (BPD: 22%, SPD: 21%)), panic disorder: 4 (15% (BPD: 17%, SPD: 14%)), social phobia: 2 (8% (BPD: 9%, SPD: 7%)), dissociative disorder: 2 (8% (BPD: 9%, SPD: 0%)), and generalized anxiety disorder: 1 (4% (BPD: 4%, SPD: 7%)). The neurotic symptoms identified in the charts of the subjects were as follows; symptoms of social phobia: 11 cases (42% (BPD: 43%, SPD: 43%)) including 6 with anthropophobic symptoms (23% (BPD: 26%, SPD: 36%)), obsessive compulsive symptoms and diffuse and floating anxiety: 9 (35% (BPD: 39%, SPD: 38%)), panic attacks: 8 (31% (BPD: 35%, SPD: 36%)), conversion symptoms: 7 (27% (BPD: 30%, SPD: 21%)), dissociative episodes: 6 (23% (BPD: 26%, SPD: 7%)), depersonalization: 5 (19% (BPD: 22%, SPD: 14%)), multiple apprehensive expectations: 4 (15% (BPD: 17%, SPD: 14%)), derealization: 3 (12% (BPD: 13%, SPD: 14%)), hyperventilation attacks: 3 (12% (BPD: 13%, SPD: 7%)), and somatization: 1 (4% (BPD: 4%, SPD: 7%)). In short, 54% (BPD: 61%, SPD: 43%) of the subjects had comorbid neurotic disorders, and 92% (BPD: 91%, SPD: 93%) reported at least one, and 54% (BPD: 61%, SPD: 50%), more than two kinds of neurotic symptoms, though no specific symptom correlating with BPD or SPD diagnosis was found. These findings suggest that neurotic symptoms and neurotic disorders cannot be ignored as peripheral in the borderline symptomatology. By analyzing in detail the neurotic experiences, the author pointed out as their characteristics, ego syntonicity, deterioration of reality sense and symptomatic polymorphism, ambiguity and multiplicity (panneurosis). In the symptoms the author observed signs of defective personality functioning such as disavowal of reality, low anxiety tolerance, various forms of identity disturbances. The findings counted above, suggest that the borderline neurotic symptoms are more severe in nature than those of neurotics, and could be situated in between neurotic and psychotic levels of symptomatic severity. The results indicate that the neurotic experiences of borderline patients are, as a whole, deeply ingrained in the borderline psychopathology. PMID- 1438599 TI - [Conceptual vs. indexical symptomatologies of schizophrenia]. AB - We discussed the difference of conceptual and indexical symptomatologies of schizophrenia through critics upon the theory of Eugen Bleuler, the diagnostic schema of Kurt Schneider and several recent theories of negative symptoms of schizophrenia. The notion of the group of schizophrenia of Bleuler, which is a descriptive expression of the phenomenon originally grasped in the inter-human relationships, is of conceptual value but confusing when used indexically for the definition of the illness. In the diagnostic concept of Schizophrenia by Schneider, although he explicitly sought for indexical value without any conceptual prejudice, Jaspers' notion of the psychoses defined by understandability is implicitly included. Schizophrenia is regarded as a form of psychosis which is, following Jaspers, a synonym of madness. Since then, the value of Schneider's 1st rank symptoms has been generally acknowledged and they have contributed to the development of operational diagnostic criteria of schizophrenia. However, the general neglect of unproductive symptoms has caused a new stream of operational symptomatology, namely negative symptoms. This stream includes not only biological researches but also ideological investigations of the essential disturbance of schizophrenia, which have been totally ignored in the operational symptomatology. The discussion of negative symptoms of schizophrenia is complexed because it contains both indexical and conceptual symptomatologies: this very complexity also contains the possibility of the integration of these two apparently distant methods. PMID- 1438600 TI - [Gonadal function in young female affective illness associated with the menstrual cycle--in relation to the polycystic ovary syndrome]. AB - The hypothalamo-pituitary-gonadal axis was studied in 10 young manic-depressive or psychotic women whose symptoms obviously fluctuated in association with the menstrual cycle. The common clinical features of these cases were (1) young female aged between 15 and 25, (2) the symptoms fluctuated obviously in association with the menstrual cycle, and (3) severe manic-depressive, or psychotic symptoms. While, in two cases, the depressive or psychotic phases had repeated many times for several years, the rest eight cases did not have a long psychiatric past history. The common hormonal features among these 10 cases were elevated basal LH (7 of 10 cases), decreased basal FSH (6 of 10), greater response of LH and normal response of FSH to LHRH (8 of 8), lack of or insufficient increase of progesterone in the luteal phase (7 of 8), and elevated serum testosterone (5 of 10), androstenedione (4 of 10) and DHEA-S (3 of 9). These abnormalities resemble those of polycystic ovary syndrome (PCOS). Five of the 10 cases showed mild hirsute signs such as mustache, acne, and/or well developed musculo-skeletal system. An ultrasonographical study revealed polycystic changes in 7 of 10 cases. Ordinary psychotropic pharmacotherapy was not effective sufficiently and hormonal therapy was tried in these 10 cases. Clomiphene citrate was administered on Day 5-9 of the menstrual cycle at a daily dose of 50mg orally in 9 cases, and it was effective to prevent recurrence of manic episode in one case, and to improve manic-depressive or psychotic symptoms in 6 cases. In these 6 cases, the effects were commonly observed within 1 or 2 weeks subsequent to the administration being completed. Daily dexamethasone administration was effective in one case with high serum DHEA-S level in whom clomiphene citrate worsened the psychotic symptoms, and thyroid hormone was effective in one case. In comparison with the pathophysiology of PCOS, a possible relationship was suggested between psychiatric problems and the PCOS-like hormonal abnormalities in these cases. PMID- 1438601 TI - [Informed consent in psychiatric treatment--a study on ECT]. PMID- 1438602 TI - A clinical approach to help psychiatric patients with smoking cessation. AB - In this paper we briefly review the dynamics of smoking and nicotine dependence, discuss the evaluation of the addicted smoker, and describe interventions to facilitate the attempt to quit smoking. We also discuss the interface of psychiatric illness and smoking, particularly among those chronically hospitalized in psychiatric institutions, and suggest a rational approach to help patients with psychiatric illness stop smoking. PMID- 1438603 TI - Integrated services for treatment of schizophrenic substance abusers: demographics, symptoms, and substance abuse patterns. AB - We have previously described a model of outpatient integrated treatment for patients with comorbid psychoactive substance use disorders and schizophrenia (PSUD/S)(1). Here we review relevant literature on comorbidity and outline the rationale for integrated services. Further, we describe results from 3 related studies: First, we document the approximate incidence of PSUD among a heterogeneous group of 602 schizophrenic inpatient admissions to our hospital. Second, we describe in greater detail the psychiatric symptoms and patterns of substance abuse among a subsample of 106 inpatients with PSUD/S, contrasting them with 112 patients with PSUD and mixed psychotic disorders, but who are not schizophrenic. Third, we present a prospective research project and describe a sample of 30 patients with PSUD/S, detailing demographic characteristics, psychiatric symptoms and substance abuse history. Attention is given to current issues in the differential diagnosis of patients with PSUD/S using standardized instruments. PMID- 1438604 TI - Evaluating recent research on the homeless mentally ill. PMID- 1438605 TI - Clinical profile of clozapine: adverse reactions and agranulocytosis. AB - The arrival of clozapine has been one of the most significant developments in antipsychotic drug treatment since the advent of chlorpromazine ushered in the psychopharmacologic era. However, its utilization has been significantly limited and complicated by its potential to cause adverse effects and agranulocytosis in particular. It must be emphasized that clozapine has a side effect profile that is in many ways distinct from standard typical antipsychotic drugs. Side effects with clozapine are common and range from the benign to the potentially lethal. The most common side effects include sedation, dizziness, and sialorrhea during sleep; the most serious are agranulocytosis, seizures and respiratory depression. Although side effects from clozapine are not necessarily preventable, they are for the most part manageable. Even with the most serious adverse effects, proper knowledge of the medication's actions, clinical vigilance, and prompt intervention can prevent the occurrence of significant morbidity and mortality as a consequence of clozapine treatment. PMID- 1438606 TI - Neuropsychiatric rehabilitation for persistent mental illness. AB - The benefits of new knowledge on the psychobiology and neuropsychology of serious mental illnesses have been slow to impact on psychiatric rehabilitation technology. A literature review reveals that, at least in the case of schizophrenia, enough is known about neurobiological deficits and their impact on neurocognitive functioning to justify a more informed approach to psychiatric rehabilitation. Essential elements for a program of research are presented and preliminary data are reported examining the prevalence of executive deficits, correlations between neuropsychological deficits and social adjustment, and the nature of socially stigmatizing neuromotor deficits and their reliable assessment. In addition, early experience with the remediation of executive deficits is described and suggestions are made for future developments in this area. The authors conclude that barriers to the integration of knowledge from biological psychiatry and psychiatric rehabilitation have been largely related to academic "cultural" isolation, and that active cross fertilization of ideas is clearly justified by the present state of knowledge. PMID- 1438607 TI - The neuropsychiatric manifestations of Lyme borreliosis. AB - Lyme borreliosis (Lyme disease), a tick-borne spirochetal illness, has multisystemic involvement and is rapidly increasing in certain areas of the United States. Although its neurologic manifestations are becoming increasingly well recognized, its psychiatric presentations are not well known. The first section of this paper will provide an overview of Lyme borreliosis and a review of the relevant neuropsychiatric literature. The second section will provide clinical descriptions of some common neuropsychiatric symptoms as well as a discussion of the problems typically faced by patients with this illness. Guidelines to assist the clinician in working with these patients will be presented. PMID- 1438608 TI - [Epidemiology of alcoholism in Voralberg. Comparison of administrative incidence 1967, 1977 and 1987 in a regional psychiatric hospital]. AB - We report on the administrative incidence of alcoholism as registered by admissions for treatment in the regional psychiatric hospital, in Vorarlberg, caring for approximately 330,000 inhabitants. 1967, 1977 and 1987 were chosen as years of observation, thus describing the regional development of alcoholism in the last 20 years. Selected epidemiological data are compared to those of local population. Over the years a vast increase in admissions and treatments was registered--a result of changes in information on the addiction itself and improvement in facilities, staff and medical care in general. Whereas female involvement has sharply risen as compared to earlier decades, it now appears to have studied at a rate of 3:1 (m:f). In 1987 juvenile alcoholism as rated by hospital-admissions had comparatively declined. A greater number of married alcoholics in more qualified positions decided on treatment. Concordant somatic and psychiatric diseases are discussed. The results stress the importance of different approaches to motivation and treatment in this complex phenomenon. PMID- 1438609 TI - ["Endogeniform" affective psychoses and normal pressure hydrocephalus]. AB - Four patients with neuroradiological evidence of normal pressure hydrocephalus and psychiatric diagnosis of affective psychoses with major depression--like characteristics are presented. Three patients underwent shunting operations following an observation period of 2 to 6 years. During the post-operative follow up of 3 to 7 years, resp., no clinical changes were noted. In our opinion, and following critical evaluation of the available literature, major depression--like affective disorders in normal-pressure hydrocephalus are not influenced by shunting operations, unless they occur simultaneously as an additional symptom in an Adams-Hakim syndrome with definite progression. PMID- 1438610 TI - [Myasthenia gravis in the frontier of psychiatric diagnosis]. AB - Retrospectively 20% of more than 200 patients with myasthenia gravis reported being initially diagnosed as having a psychiatric disorder. Younger women are significantly most at risk of a psychiatric misdiagnosis whereas men are more often subject to somatic misdiagnoses. The sample's mean duration of the disease was 10 years. Nevertheless misdiagnoses still coincide with higher depression scores. Depression is also related to the dosage of anticholinesteratic medication as well as to the self-reported muscular weakness. Personality assessment through an inventory reveals only slight emotional instabilities and no illness specific profiles. PMID- 1438611 TI - [Diagnostic inquiries in patients with a theta ground rhythm variant in the EEG]. AB - Basing on the examination of 82.767 EEGs, 118 patients with theta rhythm variant (GRV) were found out. From their case-histories all particulars taken to be important were gathered by means of a questionnaire. In addition to this 70 of these patients were interviewed, mostly in the course of a visit at home, in order to supplement the data by catamnestic informations. Moreover, attending family doctors were asked for informations, and from 14 patients elsewhere recorded EEGs were evaluated. RESULTS: With regard to its cycles per second, the GRV proved to be stable even for long periods, but as to its coming to the fore a slight changeability revealed. Concerning physical complaints, the patients primarily suffered from headache, giddiness, and liability to fainting fits, secondary they frequently were affected with vegetative disorders and stomach complaints. In view of the psychic aspect striking often came to light unrest, lack of vitality, disturbed social contacts, sexual problems, anxiety fits, depressive reactions, and suicidal thoughts. High sensitiveness and insufficient self-sureness in many cases were conspicuous attributes. In particular men often failed in establishing or maintaining intimate human relations, so that many of them remained single, made at best only few friends, and easily became outsiders. Inability to enforce own desires against opposition, liability of mood, ill humor, discontent, or even jealousy frequently made their appearance. As to gainful employment and professional status several of them were less successful than their siblings and their parents. PMID- 1438612 TI - [Undetected physical diseases in new psychiatric admission]. AB - We report on clinical observations from a 10-bed psychiatric acute ward where predominantly patients with concurrent physical diseases are treated. Of 287 patients admitted within 18 months we detected serious physical illness previously unrecognized or at least not sufficiently diagnosed in 15 cases (5.2%; age 17-88 years; 4 m, 11 f). Six patients suffered from acute neurological disease. One or more extracerebral disorders were found in nine cases. 14 of the 15 patients presented with organic mental syndromes classified according to ICD-9 (acute organic psychosis: n = 8, chronic organic psychosis: n = 6). The physical diseases unknown at admission were the only cause of the acute organic psychoses while they were contributing to the development of psychiatric symptoms in the majority of the other patients. In 14 patients the diagnosis of the previously unrecognized illnesses led to a significant change of therapy. At discharge 10 patients had improved with regard to their somatic and mental state while in two cases only the physical symptoms had remitted. One patient remained completely unchanged and two patients died from their serious diseases. Our case studies illustrate the fact that a relevant proportion of newly admitted psychiatric patients suffers from life-threatening medical illnesses. These require prompt and specific interventions and can only be detected by early and thorough physical examination. PMID- 1438613 TI - [Comment on: Psychiatric diseases in HIV infected patients by J. F. Gruner]. PMID- 1438614 TI - Plasma cholinesterase isozymes and REM latency in schizophrenia. AB - The relation between electroencephalographic sleep parameters and plasma cholinesterase isozymes was examined in a group of 19 unmedicated schizophrenic patients. Rapid eye movement (REM) latency was found to be significantly inversely correlated with isozyme 3 (mainly acetylcholinesterase). The results are discussed in relation to cholinergic involvement in the regulation of REM sleep and in the pathophysiology of schizophrenia. PMID- 1438615 TI - Urinary catecholamines and cortisol in parasuicide. AB - A relationship of urinary catecholamines and of urinary free cortisol with violent suicide attempts has been reported. We have reexamined this issue in patients within 24 hours of hospital admission. Suicide attempters had significantly higher norepinephrine (NE: mean +/- SD = 58.3 +/- 27.0 micrograms/24 hours; n = 27) than did control patients with suicidal ideation (mean +/- SD = 37.1 +/- 21.3; n = 10). Among suicide attempters, those who used physical means had the highest NE levels (mean +/- SD = 69.7 +/- 21.3) and those who took overdoses of antidepressants (mean +/- SD = 51.9 +/- 17.3; n = 6), benzodiazepines (mean +/- SD = 65.1 +/- 29.7; n = 5), or miscellaneous drugs (mean +/- SD = 59.1 +/- 36.5; n = 11) had lower NE values. In contrast to NE, urinary dopamine (mean +/- SD = 402.6 +/- 392 micrograms/24 hours, epinephrine (EPI: mean +/- SD = 14.3 +/- 4.0 micrograms/24 hours), the NE/EPI ratio (mean +/- SD = 8.3 +/- 0.9), urinary free cortisol (mean +/- SD = 157.9 +/- 11.5 micrograms/24 hours) and serum cortisol (mean +/- SD = 35.0 +/- 13.1 nM/l) did not differ between groups. There were no group differences in age (mean +/- SD = 36.3 +/- 16.5 years), Beck Depression Inventory score (mean +/- SD = 26.3 +/- 12.9), Beck Hopelessness Scale score (mean +/- SD = 10.0 +/- 5.6), Beck Scale for Suicidal Ideation score (mean +/- SD = 13.6 +/- 9.3), or Hamilton Rating Scale for Depression score (mean +/- SD = 19.5 +/- 9.8). In the four parasuicide groups, there was no difference in suicide intent (mean +/- SD = 13.3 +/- 7.9). These findings indicate that there is increased NE output shortly after suicide attempts. Previous reports of a low NE/EPI ratio in suicidal patients may reflect adaptive changes rather than the acute state of the patient at the time of the attempt. PMID- 1438616 TI - Sleep in spousally bereaved elders with subsyndromal depressive symptoms. AB - Spousal bereavement in late life frequently leads to major depression. However, many people suffer from "minor" depressive symptoms that entail considerable suffering even in the absence of syndromal major depression. We describe longitudinal electroencephalographic (EEG) sleep and clinical evaluations in 14 elderly, recently spousally bereaved subjects who were experiencing subsyndromal depressive symptoms. While subjects did not meet diagnostic criteria for syndromal major depression, they did have mildly elevated scores on the Hamilton Rating Scale for Depression (mean = 10.6, range = 8-16) at the time of initial sleep studies (T1), which were carried out, on average, 5.5 months after loss of the spouse. Entry into the study was limited to volunteers who did not have a personal history of major depression or psychiatric disorder. Twelve subjects underwent followup clinical and EEG sleep evaluations (T2), 9.9 months after spousal loss. Fifty percent continued to show depressive symptoms at 6-month followup. Test-retest comparisons of sleep and clinical measures were made with a group of sex- and age-matched control subjects who were neither bereaved nor depressed. EEG sleep measures did not significantly correlate with time from loss of spouse, severity of depressive symptoms, or subjective sleep quality. Analysis of variance with repeated measures detected a significant group X time interaction effect for delta sleep ratio (decreasing in controls but increasing in the bereaved). PMID- 1438617 TI - Electroretinography in seasonal affective disorder. AB - Retinal mechanisms have been hypothesized in the pathophysiology of seasonal affective disorder (SAD). Electroretinography (ERG) is a noninvasive electrophysiologic test that provides an objective measure of photoreceptor and retinal function. We conducted dark-adapted ERG examinations with a bright white light stimulus in a group of depressed, drug-free patients with seasonal affective disorder (6 men, 18 women) diagnosed by DSM-III-R criteria, and a group of sex- and age-matched control subjects (6 men, 16 women) during the winter. A significant difference was found between SAD patients and controls, but female SAD patients had lower ERG b-wave amplitudes than female controls, while male SAD patients had higher amplitudes than the matched controls. The ERG b-wave implicit times (times from onset of stimulus to peak of b-wave) were significantly longer in the left eyes of the male control subjects. These data may indicate subtle retinal changes in patients with SAD, but the results must be considered preliminary because of the small number of subjects studied and the large intersubject variability in the ERG procedure. PMID- 1438618 TI - Functional interrelationship of serotonin and norepinephrine: cortisol response to MCPP and DMI in patients with panic disorder, patients with depression, and normal control subjects. AB - The relationship between norepinephrine (NE) and serotonin (5-hydroxytryptamine; 5HT) functioning was explored in a neuroendocrine challenge paradigm. Ten normal control subjects, 17 patients with major depression, and 22 patients with panic disorder volunteered to participate in this study. Each subject received a challenge with meta-chlorophenylpiperazine (MCPP; 0.25 mg/kg, p.o.), a 5HT agonist, and desmethylimipramine (DMI; 75 mg, i.m.), an indirect NE agonist, in randomized order. The peak-minus-baseline cortisol response to MCPP was used as an indicator of 5HT function, and cortisol response at 75 minutes-minus-baseline to DMI was used as an indicator of NE function. The cortisol responses to DMI and MCPP were found to be highly negatively correlated in the total sample, in particular in the patients with major depression and panic disorder. This finding suggests that the functions (or dysfunctions) of the NE and 5HT systems may not be separate as is usually believed, and that the NE and 5HT disturbances observed in major depression and panic disorder may not be independent. Rather, there may be a joint disturbance of NE-5HT in these disorders. PMID- 1438619 TI - Disengagement of attention in chronic schizophrenia. AB - Posner et al. (1988) recently found a lateralized impairment in the shift of covert visual attention to the right visual field in acute schizophrenic patients. Strauss et al. (1991) did not find this lateralized attentional deficit in remitted neuroleptic-treated chronic schizophrenic outpatients. The present study examined the covert shifting of visuospatial attention in clinically ill inpatients with chronic schizophrenia and in nonpsychotic control subjects. Although patients with schizophrenia were slower in all conditions, no lateralized attentional abnormalities were found. Taken together, these studies suggest that neuroleptic treatment may affect a lateralized attentional impairment in chronic schizophrenia. PMID- 1438620 TI - Disruption of saccade production during oculomotor tracking in schizophrenia and the use of its changes across target velocity as a discriminator of the disorder. AB - A clear measure of eye movement disorder (EMD) that reliably separated schizophrenic individuals from others would both give insight into the brain control of the disorder and provide an aid in diagnosis. In the present study, a detailed analysis was carried out of the interactions between the pursuit and saccadic components of eye movements at different target velocities. The subjects comprised schizophrenic patients, unipolar depressed patients, and normal controls. The speed of the slow pursuit component did not differ among the groups, but schizophrenic subjects made more saccadic movements at low target velocities, though they started further away from the target at high target velocities. On the basis of these differences, a slope was computed of the linear function that related the number of saccadic eye movements to the velocity of a ramp visual target. Slope direction was negative for schizophrenic subjects but positive for unipolar depressive and normal subjects, and the correct classification rate for subjects was 84%. PMID- 1438621 TI - Negative symptoms and the early course of schizophrenia. AB - To determine the usefulness of including a duration criterion in the definition of "negative" symptoms, the prognostic significance of a longitudinally obtained measure of negative symptoms was compared with a cross-sectionally obtained measure. As predicted, the presence of negative symptoms based on longitudinal observation was associated with most aspects of 18-month course in a group of "first-episode" schizophrenic individuals, whereas cross-sectional levels of negative symptoms were not. The findings suggest that negative symptoms, when operationalized as a trait-like phenomenon, help to portend a poor course of illness. PMID- 1438622 TI - Dysphoria: a major symptom factor in persons with disability or chronic illness. AB - Depression frequently is diagnosed in persons with chronic illness or following the onset of disability. The overlap of symptoms of many chronic illnesses and disabling conditions with depression may lead to an overestimation of depression in such populations. Some investigators have proposed revised criteria for diagnosing depression in these conditions without an understanding of the contribution of diagnostic criteria in disabling conditions. This study investigated the nature of depressive symptom criteria constellations by individually factor analyzing the Inventory to Diagnose Depression (based on DSM III diagnostic criteria) in spinal cord injury (n = 134), rheumatoid arthritis (n = 78), student (n = 140), and community (n = 150) groups. A four-factor solution emerged, with the first factor labeled "dysphoria" being represented by symptoms of negative self-evaluations, depressed affect, and suicidal ideation. The results indicate that a core element of the syndrome of depression is dysphoria, which suggests that the contribution of somatic items may be less important to the identification of the depressive syndrome in chronic illness. PMID- 1438623 TI - Smoking in patients with panic disorder. AB - We compared smoking prevalence in 217 patients with panic disorder with that in 217 age- and sex-matched control subjects who were obtained by telephone survey from the same neighborhoods. Data were obtained for current smoking habits and smoking status at either the onset of illness (patients) or 10 years previously (control subjects). Patients had been ill for 10.6 (SD = 10.0) years. Female patients with panic disorder had a significantly higher smoking prevalence at the onset of their illness than did control subjects 10 years previously (54% vs. 35%). The current smoking prevalence for female patients was also significantly higher than that of control subjects (40% vs. 25%). Male smoking rates did not differ between patients and control subjects. Caffeine use did not appear to explain these findings. These data suggest a link between smoking behavior and panic disorder in women. PMID- 1438624 TI - Neuroendocrine responses to challenge with dl-fenfluramine and aggression in disruptive behavior disorders of children and adolescents. AB - Prolactin (PRL) and cortisol (CORT) responses to a single oral administration (1.0 mg/kg) of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated prepubertal and adolescent males with disruptive behavior disorders (DBD). Neuroendocrine responses were correlated with scores on aggression rating scales in prepubertal and adolescent DBD patients and compared with those of matched adolescent normal control subjects. Net dl-fenfluramine-induced PRL and CORT release was not correlated with aggression rating scores in prepubertal and adolescent DBD patients and did not differ significantly between adolescent DBD patients and normal control subjects. Although the present study does not demonstrate a serotonergic abnormality in aggression or DBD, this may be more a reflection of limitations of the neuroendocrine challenge test procedures or the methods used than evidence that serotonergic function in the central nervous system is normal in aggression. PMID- 1438625 TI - Pupillary constriction during haloperidol treatment as a predictor of relapse following drug withdrawal in schizophrenic patients. AB - It has been proposed that the autonomic nervous system is dysregulated in schizophrenia. We hypothesized that measures of autonomic function, even during neuroleptic stabilization, might predict relapse following withdrawal of medication. Previously, shorter latencies to maximum pupillary constriction have been reported to differentiate acutely hospitalized schizophrenic patients from control subjects. Pupillary light reactions were recorded weekly from 19 chronic schizophrenic inpatients who were initially maintained on haloperidol and subsequently were withdrawn from medication under double-blind, placebo controlled conditions. Patients were then classified as either relapsed or nonrelapsed (clinically stable) during the drug-free period. During the treatment phase, a shorter latency to maximum pupillary constriction significantly distinguished patients who were later to relapse from the nonrelapsers. The potential use of autonomic activity as an indicator of prodromal sensitivity was supported. In addition, these findings emphasize the need for classification of drug-free patients according to clinical status. PMID- 1438627 TI - An interview with Ernest Wolf. Part I: The early years. Interview by Virginia Hunter. PMID- 1438626 TI - Pupillometry in identical twins. PMID- 1438628 TI - Sublimation: Winnicottian reflections. PMID- 1438629 TI - Psychoanalytic science: from Oedipus to culture. PMID- 1438630 TI - Sadomasochism and complementarity in the interaction of the narcissistic and borderline personality type. AB - The narcissist and borderline personality types complement one another's defensive style providing needed defensive externalization of disavowed and split off feelings. One is exploitative, grandiose, and dominant, forever seeking admiration and exhibiting an aggrandized self; the other experiences humiliation, neediness, helplessness, and terror of aloneness. They form a powerful complementary dyad wherein each identifies with disavowed emotional experiences displayed in the other. They can coexist for lengths of time, defensively discharging unwanted feelings. In the first case presented above, the transference was split initially, with the masoborderline patient being victimized and humiliated by her sadonarcissistic lover. In the second case, a male sadonarcissist enacted disavowed feelings through relationships with masoborderline women. In both cases, defensive enactment was fed by a complementary, intense, and symbiotic relationship. Complementary dynamics can be subtle and difficult to analyze. They involve defensive identification that draws on projection, enactment, and externalization--all difficult defenses to analyze. Enactment rather than remembering is inimical to the development of insight into transference and genetic connections and must be worked through for the analysis to progress. More than the usual analytic patience and resolve is needed to work through the difficult entrapments caused by these dynamics. PMID- 1438631 TI - The aging analyst. PMID- 1438632 TI - The limbic system: emotion, laterality, and unconscious mind. PMID- 1438633 TI - The Silence of the Lambs: Clarice Starling's analysis? PMID- 1438634 TI - Frustration theory--many years later. AB - The role of frustration in learning theory, in the invigoration of behavior and in the development of learned persistence and discrimination learning, is conceptualized. This and other phenomena are facets of the larger explanatory domain of what has come to be known as frustration theory, a theory that has guided the author's own research--from behavioral to developmental to psychobiological --until the present time and has had some influence on the research of other investigators. This is a commentary on the 1st of several published theoretical papers on frustration theory. PMID- 1438635 TI - On the fit of models to covariances and methodology to the Bulletin. AB - It is noted that 7 of the 10 top-cited articles in the Psychological Bulletin deal with methodological topics. One of these is the Bentler-Bonett (1980) article on the assessment of fit in covariance structure models. Some context is provided on the popularity of this article. In addition, a citation study of methodology articles appearing in the Bulletin since 1978 was carried out. It verified that publications in design, evaluation, measurement, and statistics continue to be important to psychological research. Some thoughts are offered on the role of the journal in making developments in these areas more accessible to psychologists. PMID- 1438636 TI - The generation of visual images: a review of neuropsychological research and theory. AB - Since the advent of the view that mental imagery is a subdividable process, claims have been made that the generation of images is the domain of the left posterior hemisphere. This article examines theory and data about the neuropsychology of image generation by focusing on the main contributors to the debate. An attempt is made to make the theory and beliefs associated with each of the key figures explicit, because these have influenced the structure of research and the development of new theories. Support is found for the involvement of the left hemisphere, although many researchers claim that the posterior regions of both hemispheres contribute to image generation but that they do so in different ways. The nature of this difference remains the subject of ongoing research. PMID- 1438637 TI - Forgetting of stimulus attributes: methodological implications for assessing associative phenomena. AB - Differential responding to changes in the stimulus situation, long central to the concept of stimulus control, also provides the implicit conceptual basis for assessing the nature of a variety of associative relationships. However, there is substantial evidence that the perception of stimulus similarity is not a static property. Generalization gradients to contextual as well as discriminative stimuli flatten over time, and this increase in perceived similarity presumably reflects forgetting of the detailed characteristics or attributes of stimuli. Methodologically, the flattening of the gradient imposes an important constraint: The effect of a stimulus shift will be highly sensitive to the length of the delay interval between training and testing. Conceptually, the loss of memory for stimulus attributes also implies that the sources of interference in retention can increase over time. PMID- 1438638 TI - Social blushing. AB - This article reviews theory and research regarding the physiology, situational and dispositional antecedents, behavioral concomitants, and interpersonal consequences of social blushing and offers a new theoretical account of blushing. This model posits that people blush when they experience undesired social attention. Puzzling questions involving blushing in solitude, the phenomenology of blushing, types of blushing, and blushing in dark-skinned people are discussed. PMID- 1438639 TI - Depressed mothers as informants about their children: a critical review of the evidence for distortion. AB - The claim that depressed mothers have distorted, inflated, perceptions of their children's problems has been made with increasing frequency in recent years. This review explicates the significance of the depression-->distortion controversy, introduces a set of standards for evaluating distortion claims, and uses these standards to evaluate the key characteristics of 22 studies that have published data directly relevant to the distortion question. None of the studies that claimed evidence for a depression-->distortion influence on mothers' ratings of their children met the necessary and sufficient criteria for establishing distortion. This review challenges the empirical foundation for the widely held assumption that depressed mothers have distorted perceptions of their children's problems. Issues that will require reckoning in future efforts to explore the depression-->distortion question are considered. PMID- 1438640 TI - Noradrenergic mediation of the memory-enhancing effect of corticotropin-releasing factor in the locus coeruleus of rats. AB - A role for the locus coeruleus (LC) in attention and behavioral arousal has been suggested. The present study examined the effect of corticotropin-releasing factor (CRF) in the LC on memory retention of a passive-avoidance task in rats. Our results indicate that intra-LC CRF injection significantly improved retention performance. Decreases of norepinephrine (NE) levels in the hippocampus and the amygdala occurred in these animals. Intra-hippocampal 6-hydroxydopamine pretreatment did not affect memory alone, while it antagonized the memory enhancing effect of CRF in the LC. This finding suggests that the dorsal NE pathway is involved in the memory consolidation process. Similar to the effect of CRF, application of the alpha 2-adrenergic antagonist yohimbine to the LC also dose-dependently enhanced memory, suggesting that CRF improved memory through activation of NE neurons in the LC. Finally, the anxiolytic chlordiazepoxide, at a concentration that did not alter memory by itself, prevented the memory facilitating effect of CRF in the LC. Our findings suggest that the LC is an important structure in modulating learning and memory processes of passive avoidance learning in rats. CRF may enhance memory through activation of NE neurons in the LC and, at least in part, through the dorsal NE pathway. Furthermore, the LC is probably an anatomical substrate for anxiety and intra-LC CRF may enhance memory through its anxiogenic actions. PMID- 1438642 TI - Menstrual synchrony in female couples. AB - The menstrual cycles of cohabitating women have been found to synchronize, possibly through social and pheromonal mechanisms. The extent of this phenomenon, menstrual synchrony, was examined in 20 couples of lesbian women. Synchrony was very frequent, with half the subjects menstruating within 2 days of their partner. Factors related to the degree of synchrony included mutual activities, friendship and menstrual regularity. PMID- 1438641 TI - Sexual behavior in adolescent and adult females with congenital adrenal hyperplasia. AB - As part of a comprehensive interview study, 34 female patients with congenital adrenal hyperplasia (CAH) plus 14 control sisters (ages 11-41 yr.) reported on their psychosexual development and sexual orientation (90 items). Fewer patients than sisters had ever experienced love relationships and sexual activities with male partners (p < 0.05 to 0.001). Twenty percent of the patients and none of the sisters wished for and/or had had homosexual relationships; in the patients > 21 yr 44% expressed this interest (p < 0.07). For most items, patients with the salt wasting variant of CAH (SW) differed more clearly from the sisters than the simple-virilizing patients (SV). For two scales "indicating" homosexual (HOM) and heterosexual orientation (HET) and for two indices of HOM/HET differences), the patients also revealed relatively stronger homosexual and/or weaker heterosexual interests than the sisters (p < 0.05 to 0.001). Here, too, the SW/sister differences were more clear-cut. These results corroborate earlier reports on both delays in reaching psychosexual milestones and increased rates of bisexual/homosexual fantasies and experiences in CAH women. PMID- 1438643 TI - Psychological aspects of premenstrual syndrome. I: Cognition and memory. AB - Fourteen women with PMS and ten without PMS were evaluated with a battery of neuropsychological tests during the follicular and late luteal phases of two consecutive menstrual cycles. Classification was determined with NIMH diagnostic criteria and prospective record keeping. The results indicated that (1) the PMS women had significant difficulty in learning new material and this problem was not phase-dependent, (2) both groups performed better on a test of frontal lobe function during the follicular phase, and (3) mood did not account for any of the differences in cognitive functioning. PMID- 1438644 TI - Psychological aspects of premenstrual syndrome. II: Utility of standardized measures. AB - Depressed mood is a salient feature of Premenstrual Syndrome (PMS). Fourteen women with prospectively documented PMS and ten without PMS completed the short form of the Beck Depression Inventory (BDI) and the Zung Self-Rating Scale for Depression (Zung-D) during the follicular and late luteal phases of two consecutive menstrual cycles. The short form of the BDI assesses the more cognitive symptoms of depression, while the Zung-D identifies primarily vegetative symptoms. The short form of the BDI was sensitive to cyclic changes in the PMS women, while the Zung-D was not. The BDI items uniquely endorsed by the PMS women during the late luteal phase were pessimism, sense of failure, dissatisfaction, guilt, self-dislike, and indecision. The premenstrual dysphoria experienced by PMS women thus appears to be more cognitive than vegetative in nature. Finally, differential utility of standardized mood measures to detect premenstrual depression is suggested. The BDI proved to be the more sensitive measure. PMID- 1438646 TI - Major depression and subclinical (grade 2) hypothyroidism. AB - Subclinical hypothyroidism (SCH) has been reported to occur in patients with a variety of affective syndromes. However, the clinical correlates of SCH in patients with major depression have received limited attention. We therefore examined demographic, clinical and treatment response variables in a cohort of patients with unipolar, nonpsychotic major depression with and without SCH. Of 139 subjects, 19 had SCH defined as an elevated basal TSH with normal circulating levels of T3 and T4. Major depression with SCH differed from that without SCH by the presence of a concurrent panic disorder and a poorer antidepressant response. PMID- 1438645 TI - Serum levels of androgens are higher in women with premenstrual irritability and dysphoria than in controls. AB - Serum levels of progesterone, total testosterone, free testosterone, androstenedione (A2), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), 17-OH-progesterone (17-OHP), and sex hormone binding globulin (SHBG) were measured in the follicular phase, around ovulation, and in the luteal phase of 11 women with severe premenstrual irritability and dysphoria and in 11 age-matched controls with no premenstrual complaints. Serum levels of free testosterone were significantly higher in the subjects with premenstrual syndrome (PMS) than in the controls in the luteal phase (p < 0.01), the follicular phase (p < 0.05), and around ovulation (p < 0.01). DHEA levels were significantly higher in the PMS subjects, as compared to controls, around ovulation (p < 0.05), while 17-OHP levels were higher in the PMS women in the luteal phase (p < 0.05). With respect to the other steroids measured, as well as SHBG, no differences between PMS subjects and controls were found. These results indicate a possible involvement of androgens in the pathophysiology of premenstrual irritability and dysphoria. PMID- 1438647 TI - A double-blind, placebo-controlled study of the effect of imipramine on TRH induced urinary urgency in healthy men. AB - We studied the effect of imipramine (IMI) on thyroid releasing hormone (TRH) induced urinary urgency as a way of investigating the mechanism of the beneficial effect of IMI on enuresis. In a double-blind study, 12 normal, healthy men between 21 and 39 yr of age ranked their urge to urinate at 30-sec intervals following IV injection of TRH (500 micrograms) or saline. The subjects then were randomly assigned to either IMI (1 mg/kg) or placebo groups for 10 days, and the procedure was repeated. Compared to saline, TRH produced a significant elevation in urinary urgency in all subjects. IMI did not significantly blunt TRH-induced urinary urgency. Thus, the mechanism by which IMI affects enuresis is likely not mediated at the level of the urinary urgency induced by TRH. PMID- 1438648 TI - Clinical evidence for thyroid dysfunction in patients with seasonal affective disorder. AB - Of 49 consecutive patients over a 21-mo period satisfying conservative criteria for seasonal affective disorder (SAD), a well-characterized syndrome involving seasonal neurovegetative dysregulation, 17 (35%) were found to have elevated serum TSH compatible with mild primary hypothyroidism (TSH > 4.6 microIU/ml). An additional eight patients (16%) met criteria for "conjectural" hypothyroidism (TSH > 3.5 microIU/ml or exaggerated TSH response to TRH). The frequency of cases with supranormal TSH within the SAD group, both with and without inclusion of the "conjectural" cases, proved statistically significant when compared to that within psychiatric patients not satisfying criteria for SAD (N = 381) or to that within the population at large. The author suggests that SAD may in part represent a reformulation in modern neuropsychiatric terms of a previously noted fall-winter decrement, both biochemical and clinical, among hypothyroid patients. PMID- 1438649 TI - Melatonin, cortisol and prolactin response to acute nocturnal light exposure in healthy volunteers. AB - An investigation of the cortisol and prolactin responses accompanying acute melatonin suppression by light (600 lux) in humans is described. Light given from midnight to 0300h suppressed nocturnal plasma melatonin concentrations by 65%. Despite this significant suppression of melatonin, no significant effect on plasma cortisol or prolactin concentrations was observed. These data support recent studies which argue that, if there is a relationship between melatonin, the hypothalamo-pituitary, and the hypothalamo-pituitary-adrenal axis in humans, it is neither direct nor simple. PMID- 1438650 TI - Failure to stimulate melatonin synthesis in the rat pineal gland with an adenosine analog. AB - Recent studies indicate the presence of adenosine binding sites in rat pinealocytes and an effect of their activation on pineal serotonin metabolism. However, controversial data exist, and reports suggest that the role of adenosine in pineal physiology is complex. On this basis, we evaluated the effects of an adenosine analog (N-ethyl-carboxamido-adenosine: NECA) on in vitro and in vivo melatonin production in the rat pineal gland. In the in vitro protocol, pineals were incubated with NECA (0.5 mM, 1 mM, or 2.5 mM) or isoproterenol (ISO: 10( 6)M) for 4 hr. In the in vivo experiments, animals were given NECA (1 mg/kg IP), ISO (0.5 mg/kg IP) or 1 ml saline diluent and sacrificed 2 hr later. The samples were assayed for pineal N-acetyltransferase (NAT) activity and melatonin concentrations. ISO caused the expected marked rise in NAT activity and melatonin levels in both protocols. NECA was ineffective in causing any modification of the parameters measured. We conclude that the adenosine analog NECA may not be involved in the activation of melatonin production. These data contrast with others in which NECA administration resulted in an increase in melatonin levels. The participation, if any, of the purinergic system in the physiology of the pineal gland is still far from being characterized. PMID- 1438651 TI - Adrenal activity does not mediate alarm substance reaction in the forced swim test. AB - Rats tested in the forced swim test were more immobile in fresh water than in water soiled by other rats, which presumably contained an alarm substance. Adrenalectomy did not affect the behavior of the rats in fresh or soiled water, nor did it affect production of or response to the putative alarm substance. The results of this study indicate that the adrenals do not mediate the response to, or production of the alarm substance. PMID- 1438652 TI - Oxytocin and vasopressin hexapeptide fragments have opposing influences on conditioned freezing behavior. AB - We investigated the influence of C-terminal fragments of oxytocin (OT) and arginine vasopressin (AVP) on conditioned freezing behavior. Subcutaneous injections of 0.3 microgram AVP(4-9) or OT(4-9) given to rats after shock training or before behavioral observation significantly altered fear-induced freezing behavior. Animals treated with OT hexapeptide froze less than controls, while animals treated with AVP hexapeptide froze more. These results support the concept that the hexapeptide metabolites of oxytocin and vasopressin can selectively modulate certain behavioral processes, and that these peptides have opposite effects on performance in behavioral tests designed to evaluate memory consolidation and retrieval. PMID- 1438653 TI - Growth hormone therapy in the elderly: implications for the aging brain. AB - Growth hormone (GH) secretion declines during normal aging, resulting in lower serum insulin-like growth factor (IGF)-I levels. It has been proposed that many of the catabolic changes seen in normal aging, including osteoporosis and muscle atrophy, are in part caused by the decreased action of the GH-IGF-I axis. In addition, patients with GH deficiency have increased overall cardiovascular mortality. Several investigators have initiated GH treatment for elderly patients with relative hyposomatotropinemia. Initial reports suggest that GH can increase muscle mass, improve exercise tolerance, increase REM sleep and cause an enhanced sense of well-being. The basis for neuropsychiatric changes during GH therapy may be due to a direct CNS action of GH itself, to the increased IGF-I secretion which GH elicits, or to enhanced functioning of peripheral organ systems. Long term studies will determine whether GH or IGF-I can exert a neurotrophic action in the aging brain. PMID- 1438654 TI - Effects of thyroid hormones on central nervous system in aging. AB - Support for the many relationships between thyroid hormones and brain function comes from both laboratory and clinical studies. Studies in laboratory animals provide convincing evidence for a neuroregulatory role of thyroid hormones in the brain, suggesting that they may affect behavior. This notion is supported by human studies which have revealed that the effects of thyroid hormones on brain function are most important during the development and maturation of the brain; thereafter, age does not seem to critically affect brain-thyroid hormone relationships. PMID- 1438655 TI - Effects of peripheral hormones on memory and ingestive behaviors. AB - This article explores the mechanisms by which peripheral gastrointestinal hormones produce central nervous system effects on memory and feeding. Cholecystokinin produces its satiety effects and memory-enhancing effects by stimulating ascending vagal fibers. Hyperglycemia has been demonstrated to be a cause of memory dysfunction in persons with diabetes mellitus. A number of other hormones, such as amylin and bombesin, modulate both memory processing and feeding. The causes of the anorexia of aging are briefly reviewed. PMID- 1438657 TI - Anniversaries--the biopsychosocial complementarity of keeping count and not keeping count. PMID- 1438656 TI - The birthday: lifeline or deadline? AB - This study of deaths from natural causes examined adult mortality around the birthday for two samples, totalling 2,745,149 people. Women are more likely to die in the week following their birthdays than in any other week of the year. In addition, the frequency of female deaths dips below normal just before the birthday. The results do not seem to be due to seasonal fluctuations, misreporting on the death certificate, deferment of life-threatening surgery, or behavioral changes associated with the birthday. At present, the best available explanation of these findings is that females are able to prolong life briefly until they have reached a positive, symbolically meaningful occasion. Thus, the birthday seems to function as a 'lifeline' for some females. In contrast, male mortality peaks shortly before the birthday, suggesting that the birthday functions as a 'deadline' for males. PMID- 1438658 TI - Culture and somatic experience: the social course of illness in neurasthenia and chronic fatigue syndrome. AB - An anthropological view of culture and somatic experience is presented through elaboration of the notion that illness has a social course. Contemporary anthropology locates culture in local worlds of interpersonal experience. The flow of events and processes in these local worlds influences the waxing and waning of symptoms in a dialetic involving body and society over time. Conversely, symptoms serve as a medium for the negotiation of interpersonal experience, forming a series of illness-related changes in sufferers' local worlds. Thus, somatic experience is both created by and creates culture throughout the social course of illness. Findings from empirical research on neurasthenia in China, and chronic fatigue syndrome (CFS) in the United States, corroborate this formulation. Attributions of illness onset to social sources, the symbolic linking of symptoms to life context, and the alleviation of distress with improvement in circumstances point to the sociosomatic mediation of sickness. Transformations occasioned by illness in the lives of neurasthenic and CFS patients confirm the significance of bodily distress as a vehicle for the negotiation of change in interpersonal worlds. An indication of some of the challenges anthropological thinking poses for psychosomatic medicine concludes the discussion. PMID- 1438659 TI - Culture and the psychosomatic tradition. PMID- 1438660 TI - Specificity and specification: two continuing problems in psychosomatic research. PMID- 1438661 TI - Prevalence of psychiatric disorders in early stages of HIV infection. AB - As part of a military universal HIV screening program, 442 men were assessed for the presence of DSM-III-R defined psychiatric disorders and symptoms of anxiety and depression after notification of HIV seroconversion. Of them, 84.4% were in the earliest, asymptomatic stages of disease at the time of interview (96% did not have AIDS). The Structured Clinical Interview for DSM-III-R and Structured Interview Guide for the Hamilton Anxiety and Depression Scales were used. Relevant comparisons were made to Epidemiologic Catchment Area prevalence data. HIV seropositive men were more likely than age-matched men in the community to have current diagnoses of major depression (ages 18-44) and anxiety disorders (ages 25-44). Higher lifetime rates of major depression and alcohol use disorder, and high current prevalence of sexual dysfunction (21.7%) were noted. We conclude that men who become HIV seropositive have high rates of mood and substance use disorders prior to knowledge of seroconversion, and that early in the course of HIV infection men are at risk for developing major depression, anxiety disorders, and disorders of sexual desire. PMID- 1438662 TI - Similarity of depression in diabetic and psychiatric patients. AB - Diabetic and psychiatric out-patients were studied to determine whether the symptom profile of depression was similar in medically ill and medically well subjects. The diagnosis of major depression was determined using psychiatric interviews and DSM-IIIR criteria. The 21-item Beck Depression Inventory (BDI) was used to characterize the prevalence and severity of depression symptoms, and the measure was divided into cognitive (13 symptoms) and somatic (eight symptoms) subsets. Seventeen (81%) of 21 symptoms (including 12/13 cognitive and 5/8 somatic symptoms) were not statistically different in prevalence or severity between the depressed diabetic patients (N = 41) and the depressed psychiatric patients (N = 68). Both of these depressed groups were significantly different from a nondepressed diabetic comparison group (N = 58) in the prevalence and severity of every BDI symptom except weight loss. These data show that the symptom profile of depression in diabetic patients (in particular the cognitive symptoms) is similar to that in depressed psychiatric patients and is readily differentiated from the symptom profile in nondepressed diabetic patients. Our observations support the diagnostic validity of the DSM-IIIR criteria for major depression in this medically-ill outpatient sample. PMID- 1438663 TI - Effects of stress and blood type on cortisol and VLDL toxicity preventing activity. AB - Past research has associated ABO blood type and mental stress with cardiovascular risk. We studied the effects of blood type (A vs. O) coupled with a mirror drawing stressor on very low density lipoprotein toxicity-preventing activity (TxPA) and plasma cortisol levels. Exposure to the stressor significantly decreased TxPA and increased cortisol for the total group of 25 older adult males. However, the stress response patterns of the 15 blood type A males were different from those of the 10 type O subjects. The blood type A group had higher initial levels of TxPA and cortisol as well as quicker stress recovery rates than the type O group. ABO blood type may be an important behavioral hematologic variable to assess in studies concerning biochemical stress response or cardiovascular risk. PMID- 1438664 TI - Autoimmunity in the thyroid--can the molecular revolution contribute to our understanding? PMID- 1438665 TI - Bronchoscopy and tuberculostearic acid assay in the diagnosis of sputum smear negative pulmonary tuberculosis: a prospective study with the addition of transbronchial biopsy. AB - A prospective study of the efficacy of bronchoscopy and tuberculostearic acid assay in the diagnosis of sputum smear-negative pulmonary tuberculosis (TB) was carried out in 39 patients with symptoms and radiographic changes suggestive of active pulmonary TB. The diagnosis of TB was confirmed in 15 patients, probable TB was diagnosed in eight and 16 patients did not have TB. An early diagnosis of TB was made by bronchoscopy in six patients (40 per cent). Culture of sputum obtained before bronchoscopy was positive in nine patients (60 per cent) while combined with bronchoscopy specimens, a positive mycobacterial culture was obtained in 12 patients (80 per cent). Mycobacteria were cultured from transbronchial biopsy specimens from five patients (33 per cent) but none of these was exclusively positive. Histological examination of transbronchial biopsy tissue was diagnostic of TB in four patients and it was the exclusive means of early diagnosis in two. Transbronchial biopsy also provided an alternative diagnosis in four other patients. Tuberculostearic acid assay had a sensitivity of 0.40 in bronchial aspirate, 0.80 in bronchoalveolar lavage fluid, and 0.27 in transbronchial biopsy specimens: the combined result was 0.87. In nine patients with pulmonary TB in whom an early diagnosis could not be made, the tuberculostearic acid assay was positive in seven (78 per cent). We conclude that bronchoscopy with bronchoalveolar lavage and transbronchial biopsy is helpful in providing early diagnosis and positive culture results. Assay of tuberculostearic acid in bronchoalveolar lavage fluid is a useful adjunct to early diagnosis. However, mycobacterial culture and assay of tuberculostearic acid in transbronchial biopsy specimens have little diagnostic value. PMID- 1438667 TI - Creutzfeldt-Jakob disease in recipients of human growth hormone in the United Kingdom: a clinical and radiographic study. AB - In the past 3 years there have been five further cases, in addition to one case reported in 1985, of Creutzfeldt-Jakob disease in recipients of human growth hormone in the United Kingdom. The clinical findings of two of these cases are described, demonstrating a typical presentation with a predominantly cerebellar syndrome at onset which is not commonly a presenting feature of sporadic Creutzfeldt-Jakob disease. In one case a 99mTc hexamethylpropylenamine single photon emission tomographic scan showed marked impairment of tracer uptake in the basal ganglia and cerebral cortex at a time when the clinical picture was predominantly cerebellar. This technique may be useful in early diagnosis. In the other case post mortem examination of the brain showed prominent amyloid deposition in the cerebellum, which has not been described previously in pituitary-hormone related Creutzfeldt-Jakob disease. The previously published cases of growth hormone-related Creutzfeldt-Jakob disease are reviewed and reasons for the particular clinical pattern seen are discussed. PMID- 1438666 TI - The presentation and outcome of HIV-related disease in Nairobi. AB - The range of clinical presentations of HIV-related disease in Africa has not been adequately described, despite the fact that many hospitals have to rely heavily on clinical diagnosis. Six hundred adult medical patients seen in the Casualty Department of the main Government hospital in Nairobi were enrolled in a study of the presentation and outcome of HIV-related disease: 506 of these patients were admitted, of whom 19 per cent (95) were HIV seropositive. The remaining 94 were dealt with as outpatients: 11 percent (10) of these were seropositive. A history of prior treatment for sexually transmitted disease and, if male, being uncircumcised, were associated with being seropositive. Three presentations were strongly associated with HIV infection: acute fever with no focus except the gastrointestinal tract (enteric fever-like illness), acute cough with fever (community-acquired pneumonia) and chronic diarrhoea with wasting. The WHO clinical case definition (CCD) for AIDS missed a substantial amount of HIV related morbidity (sensitivity 39 per cent) and misidentified many seronegative patients (positive predictive value 59 per cent). In comparison with the Centers for Disease Control surveillance definition for AIDS, the CCD was specific (91 per cent) and sensitive (79 per cent) but only had a positive predictive values of 30 per cent: the CCD may therefore be a poor surveillance tool for AIDS. Seropositive patients were much more likely to die than were seronegative patients (39 per cent vs. 15 per cent mortality). Enteric fever-like illness was the presentation which most commonly proved fatal. A wider spectrum of disease is associated with underlying HIV immunosuppression than has previously been described in Africa. PMID- 1438668 TI - The relationship between long-term glycaemic control and diabetic nephropathy. AB - Urine albumin excretion was studied by two widely accepted methods in 210 patients with insulin-dependent diabetes mellitus and related to the mean of serial glycosylated haemoglobin (HbA1) measurements made every 3 months during the previous 6 years. Microalbuminuria (albumin excretion rate > 20 micrograms/min) was present in 9.5 per cent of patients when defined by a 24-hour collection and 8.1 per cent of patients when defined by a timed overnight urine sample. Those with microalbuminuria, as estimated from a timed overnight urine sample, had a longer duration of diabetes but otherwise did not differ in age, duration of diabetes or arterial blood pressure from patients whose albumin excretion rate was 20 micrograms/min or less irrespective of the method of urine collection. The mean and the most recent HbA1 levels differed significantly between the normal and the microalbuminuric groups when defined by the 24-hour albumin excretion rate (p < 0.001, p < 0.01), but no significant difference between these groups was found when albumin excretion rates were calculated from the timed overnight urine sample. Albumin excretion rate, examined in relation to mean HbA1, increased significantly with worsening glycaemic control whether measured over 24 hours or overnight (p < 0.05, p < 0.01). These findings support an association between glycaemic control and microalbuminuria, but the correlation is weak, dependent on the method of urine collection and is just as good for a relatively short-term as for a long-term measure of average blood glucose. PMID- 1438669 TI - Bilateral paramedian thalamic infarction: a distinct but poorly recognized stroke syndrome. AB - Six patients with bilateral paramedian thalamic infarction were seen in a general hospital over a 4 year period. This distinct stroke syndrome was recognized by the features of disturbed vigilance, often episodic, with vertical gaze disorder. Other signs included an amnesic syndrome, convergence difficulty, third nerve palsies, eyelid retraction, dysarthria, ataxia and involuntary limb movements. Diagnosis was confirmed by CT brain scan or magnetic resonance imaging. A variety of risk factors for stroke were present. All patients improved but two had significant residual disabilities. PMID- 1438670 TI - Mechanisms of abnormal glucose metabolism during the treatment of acute severe asthma. AB - Twenty-five patients with acute severe asthma were treated with oxygen, corticosteroids and either salbutamol or aminophylline by intravenous infusion. Blood glucose, plasma insulin and glucagon were measured during the first 24 hours of treatment. Salbutamol and aminophylline rapidly caused hyperglycaemia, accompanied by a rise in insulin and a fall in plasma glucagon. At first the increase in plasma insulin was insufficient to restore normoglycaemia, but by 24 hours homeostasis was restored. The early submaximal insulin response was attributed to the fasting caused by breathlessness. There was no evidence of an increase in hormone secretion caused by direct beta 2-adrenergic stimulation of the pancreatic islets. The effect of corticosteroids on blood glucose over the period of study was considerably less than the contribution of either salbutamol, or aminophylline. PMID- 1438671 TI - The spectrum of chronic liver disease in renal transplant recipients. AB - Chronic liver disease has been reported to be an important cause of late morbidity and mortality in renal transplant recipients. We have examined the prevalence and nature of chronic liver disease among 538 patients with functioning renal allografts managed at the Western Infirmary, Glasgow, between 1980 and 1989. Thirty-seven patients (7 per cent) satisfied biochemical criteria for chronic liver dysfunction. Liver biopsies were obtained from 24 of these, and autopsy tissue was available from three other patients. Chronic hepatitis of variable severity was present in 15 patients, haemosiderosis in 12 patients and nodular regenerative hyperplasia in five patients. Nineteen patients (51 per cent) had serological evidence of infection with the hepatitis C virus, and one of these developed chronic hepatitis B and D infection as well. Although a variety of chronic liver diseases occurred in our transplant population, the frequency of serious sequelae from liver dysfunction was much lower than that reported from transplant centres in other countries. PMID- 1438672 TI - Laboratory investigation in the diagnosis of pulmonary thromboembolism. AB - Laboratory findings were compared with lung scans in a prospective study of 260 patients undergoing ventilation-perfusion (V/Q) lung scanning for suspected pulmonary thromboembolism. The best discrimination between different lung scan results was obtained from the level of plasma cross-linked fibrin degradation products, every patient with a scan indicating a high probability of thromboembolism having detectable levels. An acute phase response was demonstrated in patients with pulmonary thromboembolism by a raised neutrophil count and elevated levels of plasma fibrinogen and serum C-reactive protein. A normal level of serum C-reactive protein and/or plasma cross-linked fibrin degradation productions in blood taken within 4 days of onset of symptoms virtually excluded the diagnosis of pulmonary thromboembolism. Detection of free plasma DNA was not helpful in discriminating between groups with different lung scan results. Discriminant analysis was used to assess the variables examined and to derive diagnostic models. An accuracy of 78 per cent was obtained with one model for classifying test patients according to the three lung scan classes of low, intermediate and high probability. A second model, for distinguishing patients with a low and a high probability of pulmonary thromboembolism on the basis of lung scans, and a third for predicting those with a low probability on lung scan, were accurate in 94.6 per cent and 83.5 per cent of patients respectively. Discriminant models could be used in the diagnosis of pulmonary thromboembolism, especially when diagnostic imaging is not available. PMID- 1438673 TI - Fulminant community acquired infections admitted to an intensive care unit. AB - Disease progression, support required, prognostic indicators and survival in hospital and after discharge were studied in 53 patients with community acquired infections who required admission to the intensive care unit from the Department of Infectious Diseases between January, 1985 and August, 1991. The median age was 37 years and over two-thirds of patients were previously fully fit; 38 per cent of patients required intensive care within 6 hours of admission with rapidly progressive disease. Both APACHE II scores and number of organ systems failed were good indicators of prognosis: mortality was 85 per cent in those with three or more organ failures and 86 per cent in those with APACHE II scores of > or = 25. No deaths were observed in those with scores of < 10. Some organ failures (cardiovascular, renal and respiratory) occurred more frequently in those who died. Mechanical ventilation was required by 60 per cent of patients, inotropic drugs by 42 per cent and renal dialysis by 17 per cent. Mortality in hospital was 25 per cent with no further deaths at 6 months to 2 years. As a group these patients were young and previously fit. Deterioration was rapid, necessitating admission to the intensive care unit at short notice. Our results highlight the importance of having intensive care facilities in close proximity to infectious disease units. In contrast to many other groups of patients admitted to the intensive care unit, the overall outlook for patients with community acquired life-threatening infections is good, and long-term monitoring suggests that these patients remain well once recovery has occurred. PMID- 1438674 TI - Clinical features, complications and mortality in type 1 (insulin-dependent) diabetic patients in Addis Ababa, Ethiopia, 1976-1990. AB - Clinical features, complications and prognosis of 431 consecutively registered Ethiopian Type 1 (insulin-dependent) diabetic patients seen in the Diabetic Clinic in Yekatit 12 Hospital in Addis Ababa, Ethiopia, from 1976-1990 are reported. Male:female ratio was 1.4:1; mean age at diagnosis was 18.1 years (confidence interval (CI) 1.6) in women and 21.4 (CI 1.2) in men. A history of ketoacidosis at some time was present in 38 per cent, in 11 per cent at diagnosis of diabetes. Tuberculosis was the most common complicating illness, occurring at some time in 16.5 per cent of patients. In addition, 9.5 per cent (CI 4 per cent) were known to have diabetic retinopathy, 6.0 per cent (CI 2 per cent) nephropathy and 7.9 per cent (CI 2 per cent) neuropathy at their last clinic visit. During the 15 years of the study, 9.7 per cent of the patients have died, with a mean duration of diabetes at death of 9.2 years (CI 1.8), and an overall mortality rate of 15.5/1000 person-years of diabetes. Five-year survival was 96 per cent (CI 3 per cent), 15-year survival 82 per cent (CI 9 per cent), and 20-year survival 63 per cent (CI 17 per cent), calculated using the Cox proportional hazards model; prognosis was better in those diagnosed at a younger age (p = 0.029) and in those with a body mass index of > 19 kg/m2 on treatment (p = 0.096). PMID- 1438675 TI - Spontaneous peritonitis in cirrhotic hospital in-patients: retrospective analysis of 101 cases. AB - One hundred and one patients with cirrhosis resulting from alcohol abuse, admitted to Broussais University Hospital, Paris, between January, 1986 and December, 1989 were assessed for infection of the ascitic fluid using clinical and cytobacteriological criteria. All of 46 patients (45.5%) with clinical signs and symptoms of peritonitis had an ascitic fluid polymorphonuclear (PMN) count > 250 cells/mm3. Bacteria could be isolated from the ascitic fluid of 23 patients (50%). Twenty-six bacterial strains were isolated (there was more than one strain in two samples). Escherichia coli was found in 14 cases. It is noteworthy that no anaerobes were grown. Mortality, biochemical parameters and clinical features correlated significantly with an ascitic fluid PMN count > 250 cells/mm3. High mortality correlated with a PMN count > 1000 cells/mm3 (70% vs. 33%). PMID- 1438676 TI - Primary glomerulonephritis and hydrocarbon exposure: a case-control study and literature review. AB - A case-control study was undertaken to investigate the possible role of chronic hydrocarbon exposure and tobacco and alcohol consumption in the causation of primary glomerulonephritis. Exposure to hydrocarbons and the consumption of tobacco and alcohol were assessed blindly by telephone interview and questionnaire in 55 patients with end-stage renal disease due to biopsy-proven primary glomerulonephritis in whom there had been no evidence of systemic disease. This was compared with 55 normal subjects matched for age, sex, social class and residential area and a comparable internal control group of 45 patients with end-stage renal disease secondary to systemic disease, diabetic nephropathy or chronic pyelonephritis. Hydrocarbon exposure scores derived from the results of the questionnaires were significantly higher (p < 0.001) in the patients with primary glomerulonephritis than in the normal subjects and the internal control group. Moreover, more detailed assessment of the type of hydrocarbon exposure showed significantly greater exposure of patients with glomerulonephritis to petroleum products (p < 0.001), greasing/degreasing agents (p < 0.01) and paints/glue (p < 0.05), and a resulting estimated relative risk of developing glomerulonephritis with each type of hydrocarbon exposure of 15.5, 5.3 and 2.0. Those patients with heavy hydrocarbon exposure (hydrocarbon score > 25,000) had a significantly higher serum creatinine at presentation than those with mild to moderate exposure, suggestive of more advanced renal disease. However, there was no significant difference in tobacco and alcohol consumption among subjects in different groups. We conclude that occupational exposure to hydrocarbon is likely to play a role in the pathogenesis of primary glomerulonephritis and that the risk of developing glomerulonephritis is greatest in those subjects exposed to petroleum products. PMID- 1438677 TI - Damage to cellular DNA from particulate radiations, the efficacy of its processing and the radiosensitivity of mammalian cells. Emphasis on DNA double strand breaks and chromatin breaks. AB - For several years, it has been evident that cellular radiation biology is in a necessary period of consolidation and transition (Lett 1987, 1990; Lett et al. 1986, 1987). Both changes are moving apace, and have been stimulated by studies with heavy charged particles. From the standpoint of radiation chemistry, there is now a consensus of opinion that the DNA hydration shell must be distinguished from bulk water in the cell nucleus and treated as an integral part of DNA (chromatin) (Lett 1987). Concomitantly, sentiment is strengthening for the abandonment of the classical notions of "direct" and "indirect" action (Fielden and O'Neill 1991; O'Neill 1991; O'Neill et al. 1991; Schulte-Frohlinde and Bothe 1991 and references therein). A layer of water molecules outside, or in the outer edge of, the DNA (chromatin) hydration shell influences cellular radiosensitivity in ways not fully understood. Charge and energy transfer processes facilitated by, or involving, DNA hydration must be considered in rigorous theories of radiation action on cells. The induction and processing of double stand breaks (DSBs) in DNA (chromatin) seem to be the predominant determinants of the radiotoxicity of normally radioresistant mammalian cells, the survival curves of which reflect the patterns of damage induced and the damage present after processing ceases, and can be modelled in formal terms by the use of reaction (enzyme) kinetics. Incongruities such as sublethal damage are neither scientifically sound nor relevant to cellular radiation biology (Calkins 1991; Lett 1990; Lett et al. 1987a). Increases in linear energy transfer (LET infinity) up to 100-200 keV micron-1 cause increases in the extents of neighboring chemical and physical damage in DNA denoted by the general term DSB. Those changes are accompanied by decreasing abilities of cells normally radioresistant to sparsely ionizing radiations to process DSBs in DNA and chromatin and to recover from radiation exposure, so they make significant contributions to the relative biological effectiveness (RBE) of a given radiation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1438678 TI - Heavy ion effects on cells: chromosomal aberrations, mutations and neoplastic transformations. AB - The quantification of chromosomal aberrations, mutations and neoplastic transformations induced by heavy charged particles meets with considerable experimental and conceptual difficulties which are related to the specific pattern of energy deposition. These problems are discussed on the background of current ideas on track structure, and some new experimental results are analysed. PMID- 1438679 TI - Protection of early cellular damage in 1 Gy-irradiated mice by the elevation of extracellular adenosine. AB - In whole-body 1Gy-irradiated mice a modification of early cellular damage by means of preirradiation dipyridamole and adenosine monophosphate (AMP) treatment was investigated. Both drugs were given either alone or in combination, AMP being administered i.p. at doses of 5, 10 and 15 mg, dipyridamole s.c. at the dose of 2 mg, 20 min before AMP. The thymidine level in plasma and the amount of free polynucleotides in the thymus and spleen, both estimated at the interval of 4 h after irradiation, were used as indices of early cellular damage in vivo. The elevated level of thymidine observed in the plasma of irradiated controls decreased significantly after the administration of AMP (5 mg) alone to 71%, after the combination of dipyridamole and AMP a still deeper significant fall to 60% was observed. Such a protective effect was observed when injecting AMP 15 min before irradiation. Using the interval of 65 min between AMP administration and irradiation, no protection was detected. The higher doses of AMP (10, 15 mg) enhanced the protective effect manifested in plasma thymidine level only moderately. The amount of free polynucleotides, elevated in the thymus and spleen of irradiated mice, was significantly decreased in the thymus of mice pretreated with the combination of dipyridamole and AMP. The results suggest that the treatment used decreases the radiation damage of the sensitive thymocyte population. It is proposed that the joint use of AMP, an adenosine prodrug, and dipyridamole, a drug inhibiting adenosine uptake by cells, leads to an elevation in extracellular adenosine which activates cell surface adenosine receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438680 TI - Damage at two levels of DNA folding measured by fluorescent halo technique in X irradiated L5178Y-R and L5178Y-S cells. I. Initial lesions. AB - We examined, by the fluorescent halo assay, alterations in the nucleoid structure (structure formed from cells under mild lysis conditions: in non-ionic detergent Triton X-100, 0.0005% and 1.5 mol/l NaCl) of L5178Y (LY) cell sublines which had been untreated, treated with reducing/chelating agents (beta-mercaptoethanol or sodium diethyl dithiocarbamate (DDTC(Na))) or X-irradiated. These sublines differ in radiation sensitivity: LY-R is more resistant (D0 = 1.1 Gy) and LY-S more sensitive (D0 = 0.5 Gy). Halo diameters were measured after cell lysis in the presence of propidium iodide (PI) (0.5 to 50 micrograms/ml) at pH 6.9 or 9. The maximal DNA unwinding in PI was obtained at 7.5 micrograms/ml PI, at both pH 6.9 and 9 in both sublines; the maximal halo diameter was larger in LY-S than in LY-R cells. In nucleoids from both sublines DNA could be rewound at higher (10-50 micrograms/ml) PI concentrations both at pH 6.9 and 9. This ability was impaired by mercaptoethanol or DDTC(Na) (at pH 9) or by X-irradiation, indicating damage and/or alteration in the DNA superhelical structure. The susceptibility to reducing/chelating agents was greater in LY-S than in LY-R nucleoids, pointing to differences in chromatin structure between these sublines. The amount of X-ray inflicted damage was higher, when measured at pH 9 than at pH 6.9 and was about twice larger in LY-S than in LY-R nucleoids, when the cells were irradiated with the same X-ray dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438682 TI - Induction of SOS repair by ionizing radiation. Results from experiments at accelerators. AB - beta-galactosidase and alkaline phosphatase activities of Escherichia coli strain PQ37 carrying the fusion gene of sulA and lacZ treated with different types of ionizing radiation were examined. The induction factor (ratio of beta galactosidase to alkaline phosphatase activity), reflecting the SOS-induction potency, increases significantly with radiation dose. Maximum effectiveness to induce SOS-response has been found for deuterium and helium ions in comparison to gamma-rays, carbon or krypton ions. Increased energy of helium ions leads to greater SOS-induction potency of radiation. PMID- 1438681 TI - Thermosensitization, heat shock protein synthesis and development of thermotolerance in M-14 human tumor cells subjected to step-down heating. AB - M-14 human tumor cells have been subjected to two regimens of step-down heating (SDH) consisting of a conditioning treatment at 42 degrees C for 1 h or at 44.5 degrees C for 20 min, immediately followed by heating at 40 degrees C. Both conditioning treatments thermosensitize the cells towards the subsequent heating at 40 degrees C; the thermosensitization ratio is 6.4 for cells conditioned at 42 degrees C for 1 h and 32.3 for cells conditioned at 44.5 degrees C for 20 min. The overall protein synthetic activity is reduced to 32.7% or 18.4% of control values following 1 h at 42 degrees C and 20 min at 44.5 degrees C, respectively; this inhibition is followed by a full recovery of the synthetic activity during the subsequent exposure at 40 degrees C. SDH-treated cells synthetize four heat shock proteins, with approximate molecular weights of 28, 64, 70 and 90 kDa. The pattern of HSPs induction observed in SDH-treated cells is similar to that found in cells subjected to single hyperthermic exposures. Cells subjected to the SDH sequence 42 degrees C/1 h-->40 degrees C/4 h develop thermotolerance, as indicated by a reduced sensitivity to further hyperthermic challenges. PMID- 1438683 TI - Assessment of ideal neutron beams for neutron capture therapy. AB - The discrete-ordinates transport computer code DORT has been used to develop a two-dimensional cylindrical phantom model for use as a tool to assess beam design and dose distributions for boron neutron capture therapy. The model uses an S8 approximation for angular fluxes and a P3 Legendre approximation for scattering cross sections. A one-dimensional discrete-ordinates model utilizing the computer code ANISN was used to validate the energy-group structure used in the two dimensional calculations. In the two-dimensional model the effects of varying basic parameters such as aperture width, neutron source energy, and tissue composition have been studied. Identical results were obtained when comparing narrow beam calculations to fine-mesh higher-order Sn treatments (up to S32), and with P5 cross sections. It is shown that, when the correct assessment volume is used, narrow beams will give little or no advantage for therapy even with an optimum-energy ideal neutron beam. PMID- 1438684 TI - Dosimetry of 252Cf sources for neutron radiotherapy with and without augmentation by boron neutron capture therapy. AB - Interstitial and intracavity 252Cf sources have been used to treat a number of tumor types with encouraging results. In particular these tumors include a variety of cervical, head-and-neck, and oral-cavity cancers and possible malignant gliomas. As a neutron source, 252Cf offers certain theoretical advantages over photon therapy (i.e., in treating tumors with significant hypoxic or necrotic components). With the recent availability of 10B-labeled tumor seeking compounds, the usefulness of 252Cf may be further improved by augmenting the 252Cf dose to the tumor with an additional dose due to the fission (following thermal neutron capture) of 10B located in the tumor itself. While the high mean neutron energy permits 252Cf to deliver a high-LET, low-OER dose to the tumor on a macroscopic scale, thermalization of neutrons followed by 10B capture may augment this dose at the cellular level if adequate loading of tumor cells with 10B is possible. This paper presents results of a Monte Carlo simulation study investigating the dosimetric characteristics of linear 252Cf sources both with and without the quantitative increase in tumor dose possible with the addition of 10B. Results are displayed in the form of "along and away" tables and dose profiles in a water phantom. Comparisons of Monte Carlo results with experimental and analytical dosimetry data available in the literature are also presented. PMID- 1438686 TI - High resistance of cultured Mongolian gerbil cells to X-ray-induced killing and chromosome aberrations. AB - The Mongolian gerbil (Meriones unguiculatus) is known to be one of the most radioresistant animals. We have examined the X-ray sensitivity of normal diploid fibroblasts from Mongolian gerbil embryos compared with those of cultured embryo cells obtained from various laboratory animals and a normal human. There was a wide difference in X-ray sensitivity for cell killing among different mammalian species. The D0 values for Mongolian gerbil cells ranged from 2.08 to 2.28 Gy, values which are twice as high as those for human cells. The mean D0 value for human cells was 1.06 Gy. Mouse, rat, Chinese hamster, and Syrian/golden hamster cells showed similar D0 values ranging from 1.30 to 1.56 Gy. When cells were irradiated with X rays, ten times more chromosome aberrations were detected in human cells than in Mongolian gerbil cells. The frequencies of chromosome aberrations in other rodent cells were between the values for cells from humans and those from gerbils. These data indicate that the Mongolian gerbil cells are resistant to X-ray-induced cell killing and chromosome aberrations, and that the radiation sensitivity of mammalian cells in primary culture may be reflected by their radioresistance in vivo. PMID- 1438685 TI - 5-Nitro-4-(N,N-dimethylaminopropylamino)quinoline (5-nitraquine), a new DNA affinic hypoxic cell radiosensitizer and bioreductive agent: comparison with nitracrine. AB - Targeting of electron-affinic radiosensitizers to DNA via noncovalent binding (e.g., intercalation) may offer the potential for increasing sensitizing efficiency. However, it has been suggested that high-affinity DNA binding may compromise sensitization by restricting the mobility of sensitizers along the DNA, and by decreasing rates of extravascular diffusion in tumors. The weak DNA intercalator nitracrine (1-NC) is a more efficient radiosensitizer than related nitroacridines with higher DNA-binding affinities (Roberts et al., Radiat. Res. 123, 153-164, 1990). The present study investigates whether electron-affinic agents of even lower DNA-binding affinity may be superior to nitroacridines. The quinoline analog of 1-NC, 5-nitraquine (5-NO), was shown to have an intrinsic association constant for calf thymus DNA in 20 mM phosphate buffer which was 12 fold lower than that of 1-NC. 5-Nitraquine was not accumulated as efficiently as 1-NC by AA8 cells, but, despite a similar one-electron reduction potential, was 2 to 3-fold more potent than 1-NC as a hypoxia-selective radiosensitizer in vitro when compared on the basis of average intracellular concentration. Thus the radiosensitizing potency of 5-NQ appears not to be compromised by its low DNA binding affinity. The cytotoxic mechanisms of 5-NQ and 1-NC appear to be similar (hypoxia-selective formation of DNA monoadducts), but 5-NQ is 1200-fold less potent than 1-NC as a cytotoxin. Despite this advantage, 5-NQ was not active in vivo as a radiosensitizer in SCCVII tumors. This lack of activity appears to be due to its relatively high toxicity in vivo (intraperitoneal LD50 of 105 mumol kg 1 in C3H/HeN mice), high one-electron reduction potential (-286 mV), and rapid metabolism to the corresponding amine in mice. The in vitro therapeutic index (hypoxic radiosensitizing potency/aerobic cytotoxic potency) of this weak DNA binder was lower than that of the non-DNA targeted radiosensitizer misonidazole, suggesting that DNA targeting enhances cytotoxicity more than radiosensitization. Development of useful DNA-targeted radiosensitizers may require the exploitation of DNA binding modes different from those of the nitroacridines and nitroquinolines. PMID- 1438687 TI - Amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of linear energy transfer and dose. AB - The c-myc oncogene was previously shown to be amplified in large, later-stage carcinomas of the rat skin induced by 0.8-MeV electrons. In a panel of 70 tumors induced by neon ions (45 keV/microns), c-myc amplification was rare, and in contrast to the data for tumors induced by low-linear-energy transfer (LET) (0.3 keV/microns) radiation, showed no correlation with tumor size, growth period, or time, but was associated with radiation dose. The tissue specificity for c-myc amplification seen in tumors induced by electrons was not seen in tumors induced by neon ions. These results suggest that quite distinct molecular mechanisms operate even in late stages of carcinogenesis that depend on the LET of the inducing radiation. Furthermore, the results suggest that c-myc amplification observed in tumors induced by low-LET radiation is not a general property of rat skin carcinomas, but is linked mechanistically to the inducing radiation, even though it is not detectable until many months after exposure and tumor appearance. PMID- 1438688 TI - The effects of graded doses of 1 MeV fission neutrons or X rays on the murine hematopoietic stroma. AB - The acute radiosensitivity in vivo of the murine hematopoietic stroma for 1 MeV fission neutrons or 300 kVp X rays was determined. Two different assays were used: (1) an in vitro clonogenic assay for fibroblast precursor cells (CFU-F) and (2) subcutaneous grafting of femora or spleens. The number of stem cells (CFU-S) or precursor cells (CFU-C), which repopulated the subcutaneous implants, was used to measure the ability of the stroma to support hemopoiesis. The CFU-F were the most radiosensitive, and the survival curves after neutron and X irradiation were characterized by D0 values of 0.75 and 2.45 Gy, respectively. For regeneration of CFU-S and CFU-C in subcutaneously implanted femora, D0 values of 0.92 and 0.84 Gy after neutron irradiation and 2.78 and 2.61 Gy after X irradiation were found. The regeneration of CFU-S and CFU-C in subcutaneously implanted spleens was highly radioresistant as evidenced by D0 values of 2.29 and 1.49 Gy for survival curves obtained after neutron irradiation, and D0 values of 6.34 and 4.85 Gy after X irradiation. The fission-neutron RBE for all the cell populations was close to 3 and varied from 2.77 to 3.28. The higher RBE values observed for stromal cells, compared to the RBE of 2.1 reported previously for hemopoietic stem cells, indicate that stromal cells are relatively more sensitive than hemopoietic cells to neutron irradiation. PMID- 1438689 TI - A fourth complementation group among ionizing radiation-sensitive Chinese hamster cell mutants defective in DNA double-strand break repair. AB - The XR-V9B mutant of Chinese hamster V79 cells which exhibits hypersensitivity to ionizing radiation was isolated by the replica plating technique. The increased sensitivity of XR-V9B cells to X rays (approximately 4-fold, as judged by the D10) was accompanied by increased sensitivity to other DNA-damaging agents such as bleomycin (approximately 17-fold), VP16 (approximately 6-fold), and adriamycin (approximately 5-fold). Only a slightly increased sensitivity was observed after exposure to UV radiation, MMS, or mitomycin C (1.4-, 1.7-, and 2-fold, respectively). As measured by neutral elution after exposure to X rays, XR-V9B cells showed a defect in the rejoining of double-strand breaks (DSBs); after 4 h of repair more than 50% of DSBs remained in comparison to 5% in wild-type cells. No difference was observed in the kinetics of single-strand break rejoining between XR-V9B and wild-type cells, as measured by alkaline elution. To determine whether XR-V9B represents a new complementation group among ionizing radiation sensitive Chinese hamster cell mutants defective in DSB repair, XR-V9B cells were fused with XR-V15B, XR-1, and V-3 cells, which have impaired DSB rejoining and belong to three different complementation groups. In all cases, the derived hybrids regained the sensitivity of wild-type cells when exposed to X rays, indicating that the XR-V9B mutant represents a new fourth complementation group among X-ray-sensitive Chinese hamster cell mutants defective in DSB repair. PMID- 1438690 TI - Radiation-related ophthalmological changes and aging among Hiroshima and Nagasaki A-bomb survivors: a reanalysis. AB - The relationship of ionizing radiation to the age-related ophthalmological findings of the 1978-1980 ophthalmological examination of A-bomb survivors of Hiroshima and Nagasaki has been reanalyzed using DS86 eye organ dose estimates. The main purpose of this reevaluation was to determine whether age and radiation exposure, as measured using the recently revised dosimetry information (DS86), have an additive, synergistic, or antagonistic effect. The data in this study are limited to axial opacities and posterior subcapsular changes, for which a definite radiation-induced effect has been observed in Hiroshima and Nagasaki A bomb survivors. The best model fitting for axial opacities gives a significant positive effect for both linear dose and linear age-related regression coefficients and a significant negative effect for an interaction between radiation dose and age. Such a negative interaction implies an antagonistic effect in that the relative risks in relation to radiation exposure doses become smaller with an increase in age. On the other hand, the best-fitting relationship for posterior subcapsular changes suggested a linear-quadratic dose and linear age-related effect. The estimate of the quadratic dose coefficient shows a highly negative correlation with age, but the negative quadratic dose term is extremely small and is of little biological significance. PMID- 1438691 TI - Replication of nuclear and mitochondrial DNA in X-ray-damaged cells: evidence for a nuclear-specific mechanism that down-regulates replication. AB - The mechanism by which X rays inhibit DNA replication has been investigated in three distinct populations of DNA molecules in human cells: (a) large chromosomal DNA, (b) a population of 50-100 10.3-kb nuclear episomal plasmids per cell, and (c) a population of about 500 16-kb cytoplasmic mitochondrial DNA molecules per cell. DNA replication was inhibited by X rays in nuclear chromosomal and plasmid DNA, but not in mitochondrial DNA. The mechanism by which ionizing radiation inhibits DNA replication must therefore be nuclear-specific and is unlikely to involve diffusible low-molecular-weight substances. Since mitochondrial DNA exists in the cell as independent 16-kb circular molecules and responds to radiation as would be expected for small targets, the implication for nuclear plasmids is that their replication is regulated by a large target. A current model for DNA replication involves the movement of DNA through replication centers made up of polymerases, helicases, and associated replication enzymes that are attached to a matrix. The difference in the response to X rays between mitochondrial DNA and nuclear plasmid DNA can be explained if nuclear plasmids are tightly associated with chromosomal DNA and attached to the matrix, and are coordinately replicated. PMID- 1438692 TI - Possible closure of the JANUS reactor at Argonne National Laboratory. PMID- 1438693 TI - Failla Memorial Lecture. Redox, radiation, and reductive bioactivation. AB - A brief review is presented of the background to, and the principles involved in, the development of redox-sensitive drugs for use in cancer therapy. The role of redox processes in the action of various types of radiosensitizers and in the activation of bioreductive drugs is described. The mechanisms by which many simple hypoxic cell radiosensitizers act are believed to involve fast electron transfer processes involving DNA. Some of these agents can also function as hypoxic cell cytotoxins, although the mechanisms involved are different. These "bioreductive drugs" are activated by intracellular metabolic reduction mediated through various cellular reductases. Usually, though not always, bioreduction is favored under hypoxic conditions, and this is why many of these compounds display differential cytotoxicity to hypoxic cells. This is one of the rationales for selectivity in solid tumors. The potencies of both hypoxic cell radiosensitizers and bioreductive drugs are strongly correlated with their electron affinities. Classes of bioreductive agents of current interest are described briefly. These include simple and dual-function nitroheterocycles including the highly potent compound RB-6145, quinone-based drugs including analogues of mitomycin C, and heterocyclic compounds containing N-oxide functions. The study of bioreductive agents for potential use as adjuncts for various approaches to cancer treatment is described. PMID- 1438694 TI - Dual cell cycle checkpoints sensitive to chromosome replication and DNA damage in the budding yeast Saccharomyces cerevisiae. AB - In eucaryotic cells chromosomes must be fully replicated and repaired before mitosis begins. Genetic studies indicate that this dependence of mitosis on completion of DNA replication and DNA repair derives from a negative control called a checkpoint which somehow checks for replication and DNA damage and blocks cell entry into mitosis. Here we summarize our current understanding of the genetic components of the cell cycle checkpoint in budding yeast. Mutants were identified and their phase and signal specificity tested primarily through interactions of the arrest-defective mutants with cell division cycle mutants. The results indicate that dual checkpoint controls exist in budding yeast, one control sensitive to inhibition of DNA replication (S-phase checkpoint), and a distinct but overlapping control sensitive to DNA repair (G2 checkpoint). Six genes are required for arrest in G2 phase after DNA damage (RAD9, RAD17, RAD24, MEC1, MEC2, and MEC3), and two of these are also essential for arrest in S phase when DNA replication is blocked (MEC1 and MEC2). PMID- 1438695 TI - Radiation-induced mitotic delay: a genetic characterization in the fission yeast. AB - Radiation-induced mitotic delay is under investigation in the fission yeast, Schizosaccharomyces pombe. A large range of cell cycle- and radiation-sensitive mutants of this yeast is available to facilitate this effort. Through an examination of such mutants it has been shown that the X-ray transition point and the p34cdc2 execution point are coincident; wee1- strains are not delayed by irradiation; and the radiation-sensitive mutants rad1-1, rad3-136, rad9-192, and rad17-W are not delayed by radiation or by inhibitors of DNA synthesis, including hydroxyurea. A model is proposed: Damaged DNA generates a signal to delay mitosis which is carried by the products of the rad genes to activate the tyrosine kinase p110wee1. This in turn inactivates the serine/threonine kinase p34cdc2, thereby blocking entry to mitosis. Unreplicated DNA also initiates a signal to delay mitosis which is carried by these same rad genes but, as indicated in the literature, transmission to p34cdc2 does not require p110wee1. The delay deficient rad mutants may possess some properties of tumor suppressor genes, with implications for mutagenesis and oncogenesis. PMID- 1438696 TI - Effects of ionizing radiation on cyclin expression in HeLa cells. AB - The levels of cyclin B mRNA and protein rise rapidly in G2 + M phase, and fall at the end of mitosis. The studies described here were initiated to determine the effects of ionizing radiation on the level of cyclin B bearing in mind that the division delay induced by ionizing radiation might be influenced by the expression of cyclin B. After irradiation in S phase, the cyclin B mRNA in HeLa cells was measured as the cells proceeded through the cell cycle. Instead of the usual rise, after irradiation cyclin B mRNA levels remained low during the G2 delay. After irradiation in G2 phase, cyclin B mRNA was readily detectable although at slightly lower levels than in the controls. However, cyclin B protein was markedly decreased in amount. PMID- 1438697 TI - A radiation-induced inhibitor of chromosome condensation and nuclear envelope breakdown in HeLa cells. AB - An in vitro microscopic assay for mitosis-inducing activity in mitotic HeLa cells was developed and used to demonstrate that cells irradiated and arrested in G2 phase of the cell cycle contain an inhibitor of mitosis. This assay system has a number of advantages over other assays including the use of autologous components (HeLa nuclei and mitotic cell extracts) in contrast to the microinjection method with Xenopus oocytes and without the requirements for microinjection expertise and Xenopus oocytes. The radiation-inducible inhibitor was detected at the lowest radiation dose tested (2 Gy) with maximal activity achieved within 30 min after radiation. Inhibitor activity decayed with time after radiation (2 Gy) with no activity detected at 6 h even though the cells remained in G2 phase, suggesting that either synthesis or activation of additional components is necessary for recovery from G2 arrest. The inhibitor activity was not detected in irradiated cells treated with caffeine to induce premature recovery from G2 arrest. PMID- 1438698 TI - Diffusion of low-energy electrons in tissue-like liquids. AB - The spatial-energetic distribution of low-energy electrons was studied for a source located in a liquid medium simulating biological tissue. A time independent Boltzmann equation was used to model this distribution microscopically. Ionization was treated as a perturbation to a quasi-elastic collision process between the electron and the medium. A diffusion limit was obtained by using a scale parameter, leading to a sequence of recursive partial differential equations whose solutions, associated with a macroscopic scale, were obtained by numerical approximations. As an application, electron ranges were estimated based on these solutions and then compared with values reported in the open literature based on experimental results and on Monte Carlo calculation. Local dosimetry, i.e., the energy imparted to a volume of a sphere with radius equal to the range of low-energy electrons, of low-energy electrons from internal emitters can benefit by the knowledge of the ranges estimated for biological tissue. Auger electron emitters, for example, have been the object of a number of investigations because of their radiobiological significance. PMID- 1438699 TI - Compound dual radiation action. I. General aspects. AB - The theory of dual radiation action (A. M. Kellerer and H. H. Rossi, Curr. Top. Radiat. Res. Q. 8, 85-158, 1972) has attributed the effects of ionizing radiation on eukaryotes to the production of molecular changes (sublesions) that combine pairwise to produce injury (lesions) responsible for radiation effects. If the yield of sublesions is independent of radiation quality (as is currently assumed), dual radiation action results in the well-known proportionality between the average yield of lesions and alpha D+beta D2, where beta is a radiation independent quantity. It has, however, been observed that beta changes with radiation type. In this paper we propose an explanation of this discrepancy. Specifically, we suggest that dual radiation action-type processes where beta is variable are the result of a mechanism--termed compound dual radiation action- which consists of a sequence of simple dual radiation action processes, each process being the causative agent for the next one. The sequence, single-strand DNA breaks, double-strand DNA breaks (chromosome breaks), and exchange-type chromosomal aberrations, is one such example examined in the paper. PMID- 1438701 TI - Oncogene amplification detected by in situ hybridization in radiation-induced skin cancers in rats. AB - Amplification of the c-myc oncogene has been detected by Southern blotting in the DNA of radiation-induced skin cancers in the rat. In the current work the localization of oncogene amplification within specific cells in the different cancers and in multiple biopsies of the same cancer was studied by in situ hybridization. The amount of amplification was measured by counting grains on tissue sections hybridized in situ to biotin-labeled human c-myc third exon, rat v-H-ras, and rat v-Ki-ras probes. The in situ estimates of c-myc amplification were generally correlated with previous findings using the Southern blot method, but within each cancer only a fraction of cells exhibited amplification. Multiple biopsies of a squamous carcinoma showed amplification of v-H-ras and c-myc but not v-Ki-ras during tumor growth, but none of these oncogenes were amplified during tumor regression. The c-myc-positive cells were distributed uniformly within the cancers and exhibited a more uniform nuclear structure in comparison to the more vacuolated c-myc-negative cells. A high [3H]thymidine labeling index was found in irradiated epidermal cells on Day 7 after exposure, and yet no evidence of c-myc oncogene amplification was found in situ. No c-myc amplification was found in unirradiated normal epidermis or in irradiated epidermal cells in the vicinity of radiation-induced cancers. The data indicate that c-myc amplification is cell-specific within radiation-induced carcinomas and does not occur in epidermal cells proliferating in response to radiation exposure. PMID- 1438700 TI - The RBE-LET relationship for rodent intestinal crypt cell survival, testes weight loss, and multicellular spheroid cell survival after heavy-ion irradiation. AB - This report presents data for survival of mouse intestinal crypt cells, mouse testes weight loss as an indicator of survival of spermatogonial stem cells, and survival of rat 9L spheroid cells after irradiation in the plateau region of unmodified particle beams ranging in mass from 4He to 139La. The LET values range from 1.6 to 953 keV/microns. These studies examine the RBE-LET relationship for two normal tissues and for an in vitro tissue model, multicellular spheroids. When the RBE values are plotted as a function of LET, the resulting curve is characterized by a region in which RBE increases with LET, a peak RBE at an LET value of 100 keV/microns, and a region of decreasing RBE at LETs greater than 100 keV/microns. Inactivation cross sections (sigma) for these three biological systems have been calculated from the exponential terminal slope of the dose response relationship for each ion. For this determination the dose is expressed as particle fluence and the parameter sigma indicates effect per particle. A plot of sigma versus LET shows that the curve for testes weight loss is shifted to the left, indicating greater radiosensitivity at lower LETs than for crypt cell and spheroid cell survival. The curves for cross section versus LET for all three model systems show similar characteristics with a relatively linear portion below 100 keV/microns and a region of lessened slope in the LET range above 100 keV/microns for testes and spheroids. The data indicate that the effectiveness per particle increases as a function of LET and, to a limited extent, Z, at LET values greater than 100 keV/microns. Previously published results for spread Bragg peaks are also summarized, and they suggest that RBE is dependent on both the LET and the Z of the particle. PMID- 1438702 TI - Radiation-induced DNA single-strand breaks in freshly isolated human leukocytes. AB - Single-strand breaks are a major form of DNA damage caused by ionizing radiation, and measurement of strand breaks has long been used as an index of overall cellular DNA damage. Most assays for DNA single-strand breaks in cells rely on measuring fractionated DNA samples following alkali denaturation. Quantification is usually achieved by prelabeling cells with radioactive DNA precursors; however, this is not possible in the situation of nondividing cells or freshly isolated tissue. It has previously been demonstrated that the alkali unwinding assay of DNA strand breaks can be quantified by blotting the recovered DNA on nylon membranes and hybridizing with radiolabeled sequence-specific probes. We report here improvements to the technique, which include hot alkali denaturation of DNA samples prior to blotting and the use of carrier DNA that is non complementary to the radiolabeled probe. Our method allows both single- and double-stranded DNA to be quantified with the same efficiency, thereby improving the sensitivity and reproducibility of the assay, and allows calibration for determination of absolute levels of DNA strand breaks in cells. We also used this method to assay radiation-induced DNA strand breaks in freshly isolated human leukocytes and found them to have a strand break induction rate of 1815 strand breaks/cell/Gy. PMID- 1438703 TI - Fitting the Armitage-Doll model to radiation-exposed cohorts and implications for population cancer risks. AB - The Armitage-Doll model of carcinogenesis is fitted to Japanese bomb survivors with the DS86 dosimetry and to three other radiation-exposed cohorts. The model is found to provide an adequate description of solid cancer incidence and also, to a lesser extent, of that of leukemia as a function of radiation dose when up to two radiation-affected stages are assumed. For non-leukemias the optimal model is one in which there are two radiation-affected stages separated by two additional stages. In the case of leukemia one radiation-affected stage or two adjacent stages provide suitable fits. There appear to be significant differences between the optimal models fitted to each cohort, although there is no heterogeneity within the Japanese data set by sex, by cancer type, or by age at exposure. Low-dose and low-dose-rate population risks for a population having the cancer and overall mortality rates of the current UK population are calculated on the basis of the optimal models fitted to the Japanese data to be about 8.3 x 10( 2) excess cancer deaths person-1 Sv-1, 10.1 x 10(-2) radiation-induced cancer deaths person-1 Sv-1, or 1.40 years of life lost person-1 Sv-1. Risks for a population having the mortality rates of the current Japanese population are about 6.5 x 10(-2) excess cancer deaths person-1 Sv-1, 7.8 x 10(-2) radiation induced cancer deaths person-1 Sv-1, or 0.89 years of life lost person-1 Sv-1. It is a feature of the Armitage-Doll model, and other multistage models of carcinogenesis, that if radiation acts at more than one stage then (inverse) dose rate effects may arise as a result of interactions between the effects of a protracted dose at the various radiation-affected stages. However, it is shown in this paper that these three measures of cancer risk in general display fairly slight dependence on administered dose in the range 0.001 to 1.0 Sv and on the length of the time over which the dose is administered in the range 1 to 100 years. Dose-rate effects resulting from the protraction of a radiation exposure over many years acting on (the same) cells at various stages of a multistep process of carcinogenesis are therefore expected to be slight. Dose-rate effects which have been observed in epidemiological studies and cellular radiobiology may thus find their explanation in other phenomena such as short-term intracellular repair. PMID- 1438705 TI - Developmental changes induced by gamma irradiation in Ipomoea batatas L. Lam (sweet potato). AB - Storage roots of Ipomoea batatas L. Lam were exposed to gamma irradiation at 90, 180, and 240 Gy. The two highest doses caused a delay in the initiation of rooting and especially of shooting; they also caused formation of rosette-like, stemless shoots without apical meristems. The storage roots irradiated with 90 Gy did form stems, but 50% of them had no apical meristem. The irradiated storage roots produced absorbent roots which developed shoots after 70 days of growth. Nonirradiated storage roots did not differentiate shoots from the absorbent roots. When grown in vitro, phytomers, stem segments with leaves and an axillary meristem, separated from the shoots of irradiated storage roots and exhibited growth aberrations, very intense rooting, and a delay in shooting. Phytomers from nonirradiated normal plants were irradiated with 10, 20, 30, 40, and 90 Gy and grown in a hormone-free medium. The 40- and 90-Gy doses delayed shooting as well as rooting. Only phytomers exposed to 40 and 90 Gy differentiated shoots from the absorbent roots. A stimulation of growth revealed in the accumulation of dry mass was found in the shoots of phytomers irradiated with 10 to 30 Gy. The long after effects of irradiation as well as possible causes of growth stimulation are discussed. PMID- 1438704 TI - Low pH does not affect the dose response for 5'-amino-5'-deoxythymidine modulation of IdUrd DNA incorporation and radiosensitization in a human bladder cancer cell line. AB - We report that coincubation of 647V cells for one cell cycle with low concentrations (30 microM) of 5'-amino-5'-deoxythymidine increased IdUrd DNA incorporation and radiosensitivity at low extracellular pH (pHe 6.8) in a fashion similar to treatment at normal pHe. IdUrd DNA incorporation is inhibited by high (300 microM) 5'-AdThd concentrations at both normal and low pHe (7.4 and 6.8), resulting in no significant radiosensitization. These results at low pHe were not anticipated based on previously published studies of 5'-AdThd modulation of thymidine kinase (TK) activity and nucleoside cellular uptake. Our results suggest that regulation of intracellular pH (pHi) during the course of one cell cycle negates the 5'-AdThd dose-dependent modulation of TK activity demonstrated previously. Flow cytometric measurement of pHi in 647V cells showed that normal pHi (pH 7.4) was maintained in 647V cells over a 12- to 24-h exposure to low pHe (pH 6.8). Thus the concomitant use of IdUrd and high concentrations of 5'-AdThd (> 30 microM) is unlikely to result in selective in vivo radiosensitization of human tumors under conditions which are intermittently or chronically acidic. However, low concentrations of 5'-AdThd may prove to be an effective in vivo modulator of IdUrd radiosensitization of human tumors under both normal and acidic conditions. PMID- 1438706 TI - Neutral filter elution detects differences in chromatin organization which can influence cellular radiosensitivity. AB - We have shown previously that the neutral filter elution assay is dependent not only on the number of DNA double-strand breaks present in a mammalian cell but also on the way in which DNA expands on the filter following lysis. Results in this study indicate that the rate of DNA elution appears to be dependent upon the proximity of the DNA in relation to the replication complex. The rate of elution for DNA analyzed immediately after a 30-min labeling period with [14C]thymidine was about five times slower than the rate of elution for bulk-labeled DNA. However, the rate was increased a few hours later when the recently replicated DNA had matured and was likely to be farther from replication-associated attachment sites on the nuclear protein matrix. About one cell cycle after pulse labeling, when the labeled DNA was replicated again, DNA underwent similar changes in elution rate. For the four cell lines examined here, the elution rate 3-4 h after pulse labeling correlated with cellular radiosensitivity. Changes in rate of elution caused by altering EDTA concentration or pH may also be explained by DNA structural changes which occur during lysis. We conclude that the neutral filter elution method is sensitive to differences in chromatin organization which may also play a role in cell sensitivity to ionizing radiation. PMID- 1438707 TI - Killing of EMT-6 cells by decays from isotopes incorporated on sensitizer adducts. AB - EMT-6 tumor cell killing by decays from 3H and 125I incorporated by adduct formation of radiolabeled sensitizers was studied in vitro. Hypoxic radiosensitizers become covalently bound to cellular molecules after metabolic reduction, and EMT-6 tumor cells can tolerate over 10(9) adducts/cell of misonidazole without loss of colony-forming ability. Cells were incubated under hypoxic conditions in the presence of [3H]misonidazole or [125I]iodoazomycinriboside for various times and the amounts of bound 3H and 125I were determined. Cells were stored as monolayers at 22 degrees C, in suspension culture at 4 degrees C, and frozen in complete medium plus 8% DMSO at -196 degrees C for various times to facilitate the accumulation of radioactive decays before plating in vitro for colony-forming assays at 37 degrees C. At 22 degrees C in monolayer culture, EMT-6 tumor cells tolerated 950 and 1720 decays/cell of 3H and 125I, respectively, without evidence of radiotoxicity. This number of decays/cell over the exposure times used represents 1.54 x 10(6) 3H/cell and 8.4 x 10(4) 125I/cell, respectively. Significant cell killing was detected after similar amounts of isotope decay when cells were held at 4 degrees C. When cells were frozen in the presence of 8% DMSO, they were more resistant to inactivation by isotope decays or by gamma rays than cells in liquid phase at 4 degrees C. These data suggest that selective hypoxic tumor cell suicide by 3H or 125I decays from bound sensitizer at 37 degrees C will be an inefficient process, at least for drugs with specific activities as tested. These data are consistent with data on cell inactivation by isotopes incorporated into cells by other procedures. PMID- 1438708 TI - Decreased repair of radiation-induced DNA double-strand breaks with cellular differentiation. AB - Although the majority of mammalian cells in situ are terminally differentiated, most DNA repair studies have used proliferating cells. In an attempt to understand better the relationship between differentiation and DNA repair, we have used the murine 3T3-T proadipocyte cell line. In this model system, proliferating (stem) cells undergo growth arrest (GD cells) and subsequently terminally differentiate into adipocytes when exposed to media containing platelet-depleted human plasma. Pulsed-field gel electrophoresis was used to evaluate the induction and repair of DNA double-strand breaks (DSBs) after ionizing radiation. The levels of radiation-induced DSBs in GD and terminally differentiated cells were similar, but in both cases greater than those found in stem cells at each radiation dose tested (0 to 40 Gy); these differences appear to be due to growth arrest in G1 phase. DNA DSBs were repaired with biphasic kinetics for each cell type. For terminally differentiated cells 25% of DNA DSBs remained unrejoined compared with < 10% for GD and stem cells after a repair time of 4 h. These data indicate that terminal differentiation of 3T3-T cells is associated with a reduction in the repair of ionizing radiation-induced DNA DSBs. PMID- 1438709 TI - Protection against metastasis of radiation-induced thymic lymphosarcoma and weight loss in C57Bl/6NCr1BR mice by an autoclave-resistant factor present in soybeans. AB - We have investigated the ability of Bowman-Birk inhibitor, a protease (trypsin and chymotrypsin) inhibitor, to protect against radiation-induced thymic lymphosarcoma in C57Bl/6NCr1BR mice. Fifty-five 7-week-old male mice were randomized into 11 groups and gavaged 5 days per week with purified Bowman-Birk inhibitor, Bowman-Birk inhibitor concentrate, and autoclaved Bowman-Birk inhibitor concentrate. Following 7 days of gavage, those mice undergoing total body or sham total-body irradiation received 1.7 Gy weekly for 4 weeks. At 6 months following the radiation exposure, all mice were sacrificed and examined histopathologically. Samples of Bowman-Birk inhibitor concentrate, purified Bowman-Birk inhibitor, and autoclaved Bowman-Birk inhibitor concentrate were evaluated with thin-layer chromatography. The mice treated with total-body irradiation and autoclaved Bowman-Birk inhibitor had significantly (P < 0.05) fewer deaths, lower average grade of lymphosarcoma, and larger fat stores compared to those treated with total-body irradiation and water gavage. The results for the total-body-irradiated mice receiving Bowman-Birk inhibitor concentrate suggested an effect midway between these two groups. Thin-layer chromatography analysis indicated that sterols and the phospholipids varied in the three different samples in a way that approximately corresponded with the observed effects. We have observed that an autoclave-resistant factor in soybeans is capable of reducing metastasis of radiation-induced lymphosarcoma and weight loss in C57Bl/6NCr1BR mice, presumably by preventing the extension and metastasis of cancer cells. Thus, in addition to the anticarcinogenic Bowman-Birk inhibitor, there appears to be another anticarcinogenic agent in soybeans which is capable of inhibiting the later stages of cancer cell development. PMID- 1438710 TI - Effects of partial hepatectomy on the growth characteristics and hypoxic fractions of xenografted DLD-2 human colon cancers. AB - A recent publication by Leith et al. (Cancer Res. 51, 4111-4113, 1991) showed that administration of epidermal growth factor (EGF) (0.25 mg/kg; q.i.d. x 7) to mice bearing xenografted A431 human epidermoid cancers produced increased tumor growth and a reduction of the percentage of hypoxic cells within neoplasms. In contrast, sialoadenectomy, which removes the majority of circulating EGF in the mouse, resulted in slower tumor growth and increased hypoxic percentages. To investigate such homeostatic mechanisms further, we investigated the growth characteristics and hypoxic fractions of xenografted DLD-2 human colon tumors when tumor-bearing mice received partial hepatectomy (about 65%), unilateral nephrectomy, or nonspecific surgical trauma (laparotomy). Surgical procedures were performed when tumor volumes were about 375 mm3, and hypoxic percentages within tumors were measured by clonogenic excision assay procedures 72 h later. We found that partial hepatectomy increased the growth rates of the transplanted DLD-2 cancers by about a factor of 2.4. This increased growth rate was accompanied by an increase in the mitotic index from about 1.5 to 3.0%. Also, hypoxic fractions were decreased from 0.561 in control tumors to 0.235 in tumors from mice receiving partial hepatectomies. Unilateral nephrectomy and nonspecific surgery manipulations did not alter tumor growth rates, mitotic indices, or hypoxic percentages. These results indicate that partial hepatectomy produces significant alterations in tumor physiology. Results are consistent with a growth factor-mediated mechanism. PMID- 1438711 TI - Technique to improve lateral cervico-thoracic radiographs. AB - Lateral radiographs taken during radiotherapy simulation of the upper thoracic and lower cervical region are often of poor quality because of the difference in separation seen by the incident beam. A simple method of compensating for this is the application of a thin foil of lead on the simulator that obscures the light field in the superior portion of the field. This technique has the advantage of being simple, fast and easily reproducible. PMID- 1438712 TI - Standing up to cancer's challenge. PMID- 1438713 TI - Radiotherapy technique integrates MRI into CT. AB - The 1970s saw the introduction of computed tomography, which enabled soft tissue anatomy to be seen. Today simulation of therapeutic fields by x-ray is augmented by radiotherapy treatment planning using CT data. The 1980s brought magnetic resonance imaging with superior soft tissue contrast. This article describes a technique correlating three-dimensional MRI/CT data sets used routinely in treatment planning of tumors in the head. PMID- 1438714 TI - The profession's future: leadership development. PMID- 1438715 TI - Identification of stressors in radiologic technology. AB - Much is written about stress in the workplace, but until the causes of stress are identified, little can be done to address the problem. This article reports results of a survey of 198 randomly selected radiologic technologists who were asked to assess the relative stressfulness of 35 stressors. Disrespectful physicians, inadequate pay, unnecessary exams and lack of staff topped the list. PMID- 1438716 TI - [The importance of bone marrow examination for hemoblastoses]. AB - Morphological bone marrow evaluation is an integral component in staging patients with hematological malignancies. In acute leukemias or myelodysplastic syndromes cytologic examination is crucial since it allows precise analysis on the individual cell level. Histological examination of an iliac crest trephine biopsy is mandatory in malignant lymphomas because of the frequent nodular involvement of bone marrow in these diseases. In recent years magnetic resonance tomography (MRT) has been shown to be a sensitive method for detecting marrow infiltration in a variety of marrow diseases. In malignancies with focal marrow involvement, such as malignant lymphoma, MRT is today a useful complement to morphological bone marrow evaluation. PMID- 1438717 TI - [Bone marrow scintigraphy. Principles, clinical results and indications]. AB - After consideration of the anatomical and physiological principles, the radiopharmaceuticals for scintigraphy of the erythropoietic, reticuloendothelial and-as a new development-of the granulopoietic bone marrow are introduced and compared. The data on performing and evaluating bone marrow scans are followed by the presentation of the clinical results. Staging and re-staging of malignant lymphomas, multiple myeloma, breast and lung cancer are considered to be the main indications. 99mTc-labelled monoclonal anti-NCA-95-antibodies are regarded as the radiopharmaceutical of choice. PMID- 1438718 TI - [MR tomography of the bone marrow in malignant systemic diseases. Diagnosis and therapeutic follow-up control]. AB - This paper presents a short survey of the current status of bone marrow diagnosis in systemic neoplastic disease by means of MR imaging. The different patterns of bone marrow infiltration from lymphomas and leukaemias are presented and the differential diagnoses are discussed. Apart from the primary diagnosis the relevance of conventional MRI and chemical shift imaging for therapy follow up and after-care is discussed. PMID- 1438719 TI - [Bone marrow edema in MRT]. AB - Like other vascularized organs, bone can react with increasing interstitial fluid to disturbances in permeability caused by various noxae. Signs of bone marrow edema recognizable in magnetic resonance imaging are described for conditions such as trauma, stress, reflex sympathetic dystrophy, ischemia, and infection. A bone marrow edema may be an early or the only sign of a disease entity visible solely on MR images. We made a retrospective study of musculoskeletal MR examinations conducted over a period of 3 months to estimate the incidence of bone marrow edema. PMID- 1438720 TI - [Bone marrow changes following radiotherapy. Results of MR tomography]. AB - Magnetic resonance imaging (MRI) offers a new approach in the morphologic evaluation of the bone marrow. Physiologic and pathologic changes can be assessed with very high sensitivity. Radiotherapy induces acute depletion of the hematopoietic bone marrow, resulting in fatty degeneration. With MRI it is possible to evaluate the changes during irradiation and it also discloses the long-term fatty degeneration after radiotherapy. The irradiated bone marrow mostly exhibits a homogeneous hyperintense pattern on T1-weighted images. This allows clear recognition of the former target volumes. Our quantitative studies based on chemical shift imaging data reveal a lack of recovery of hematopoiesis after radiotherapy with 30 Gy or more. These results are independent of patients' age and of the interval after radiotherapy. PMID- 1438721 TI - [Diagnosis of pneumatosis intestinalis coli in CT]. AB - Pneumatosis intestinalis coli seldom causes symptoms of an acute abdomen and is rarely diagnosed in CT. The origin of the gas collections in the wall of the bowel often remains unclear. As shown in our case, pneumatosis may involve any portion of the bowel, but usually spares the rectum. Due to extreme meteorism and coprostasis it can be difficult to recognize pneumatosis radiographically. In CT the gas collections beneath the serosa are well defined, discrete, oval or round. PMID- 1438722 TI - [An unclear abdominal tumor. A pseudocyst in the mid abdomen caused by a retained abdominal towel from a previous cesarean section]. PMID- 1438723 TI - [Digitization of conventional x-ray films]. AB - The diagnostic value of a digitization system for analogue films based on a charge-coupled-device (CCD) scanner with adjustable resolution of 2.5 or 5 lp/mm was assessed. Some 110 skeletal radiographs, 50 contrast studies, including 25 of patients with Crohn's disease, and 70 abdominal plain films before and after successful lithotripsy for renal stones were digitized. Receiver operating characteristic (ROC) studies showed improved detection of cortical and trabecular defects with contrast-optimized digitized films. Edge enhancement algorithms yielded no additional information. Inflammatory lesions of Crohn's disease were detected equally well by conventional films and digitized images. A statistically significant improvement (p less than 0.05) in the recognition of disintegration after lithotripsy was found for the processed digitized images. On the basis of this initial investigation, the digitization system tested appears to be useful for diagnostic purposes, especially when contrast resolution plays an important part, as with stone fragmentation or cortical defects. PMID- 1438724 TI - [New developments in the computer-assisted diagnosis of focal bone lesions]. AB - Since the 1960s there have been numerous reports in the literature about computer aided medical diagnosis and therapy. However, so far computer-aided diagnosis has not become important in the clinical routine or in the field of radiology. This paper describes the hitherto existing proposals for expert systems to evaluate focal bone lesions and presents a new concept. The basic ideas of this program are: (1) a PC-based interactive dialogue along on the basis of a defined questionnaire; (2) the use of certainty factors to handle uncertainty and vagueness in evaluating the different radiological findings and their correlation with diagnoses; (3) the link between visual information and the questionnaire. The aims of such expert systems are (a) a complete and systematic analysis of the films, (b) independency of association with previously diagnosed cases in reporting the films, (c) the procurement and use of radiological descriptive terms, and (d) aid in the radiological evaluation of focal bone lesions. PMID- 1438725 TI - [Computer-assisted literature searching in radiology]. PMID- 1438726 TI - [Product of the month: scientific text processing using the MS-DOS computer]. AB - A new German word processing system, "Starwriter 6.0" for MS-DOS computers is introduced and important functions are described. The possibility of using different fonts, creating complex formulas, footnotes and endnotes, and using various functions for importing and exporting text and data files make this program highly suitable for scientific texts. PMID- 1438727 TI - [Recurrence paralysis: computed tomographic analysis of intrathoracic findings]. AB - The long and singular course of the inferior (recurrent) laryngeal nerve makes it very vulnerable to infiltration by tumors of various locations. In particular, mediastinal and pulmonary lesions must be considered in the case of left vocal chord palsy. Recurrent nerve paralysis caused by a tumor indicates advanced disease. We retrospectively reviewed the computed tomography (CT) findings in 29 patients with bronchogenic carcinoma or mediastinal tumors and recurrent nerve paralysis with respect to the site, size and extent of the tumor and the lymph node status. The review revealed a marked predominance of left upper lobe tumors with extensive lymph node metastases to the anterior mediastinum and the aortopulmonary window. The extent of mediastinal involvement exceeded the average involvement in a control group of 30 randomly selected patients with bronchogenic carcinoma at the time of presentation. In all patients CT demonstrated tumor tissue which could have caused the paralysis at one or more sites along the anatomical course of the recurrent nerve. In most cases the tumor was located at the aortic arch. The left paratracheal region, right paratracheal region and right pulmonary apex were affected in one case each. We conclude that in patients with cancer, CT is a suitable method for localizing a recurrent nerve lesion. PMID- 1438728 TI - [Measurements and variations in the region of the optic canal. CT and anatomy]. AB - This investigation of the optic canal is based on measurements of 60 macerated adult European skulls from the Alexander-Ecker Collection at the Anatomy Department of the University of Freiburg. An indian skull is also described, in which the cranial end of the left optic canal is closed by a bony plate. Computer tomographical and anatomical measurements were compared in order to assess the correlation of the two methods of investigation and the accuracy of the CT representation of osseous structures. The coronal projection of the optic canal proved to be optimal for CT examination--the sections meet the optic canal at an angle of 85.5 degrees. The measurements of transverse diameters correlate poorly, whereas vertical diameters and distances correlate well. The extent to which anatomical variations can be assessed by CT was also investigated. All anatomical variants could be observed in coronal sections, except the bony lamina in the Indian skull, which could not be seen until a contrast medium was used. The so called "keyhole anomaly" appeared in 3.3% in our material, the "figure-of-eight" variant in 2.5%, and a carotid clinoid canal in 13.3%. PMID- 1438729 TI - [An unusual bone scintigram in osteomyelitis. A case report]. AB - Despite hyperemia in the blood-pool phase of bone scintigraphy with 99mTc-MDP there was an decreased concentration of the nuclide in a 7-year-old boy with acute osteomyelitis of the femur. In addition to inflammatory destruction of the bone tissue, the other reason for this surprising scintigraphic finding might be a reduced blood flow because of thrombotic occlusion or compression of bone supplying vessels. PMID- 1438730 TI - ["Metastasizing" Echinococcus alveolar of the liver]. AB - We report a case of metastatic alveolar echinococcosis of the liver. There were calcifications of the liver parenchyma, and a large tumour adjacent to the porta hepatis infiltrated neighbouring structures. In addition, haematogenous metastases to the spine and foot were found. This extensive haematogenous "metastasis" is rare and may complicate diagnosis, but the typical findings in the liver should permit the correct conclusion. PMID- 1438731 TI - [Fistula formation and purulent pericarditis as late complications after replacement of the esophagus by retrosternal pull-up of the stomach]. PMID- 1438732 TI - [A hepatic space-occupying lesion. Liver abscess due to a retained surgical towel]. PMID- 1438733 TI - Patient monitoring during clinical MR imaging. AB - The impressive growth in the number of patients imaged with magnetic resonance (MR) technology has been accompanied by technical advances that have permitted more acutely ill patients to be studied with this diagnostic tool. Such patients, however, might require monitoring of vital functions during the examination. Unfortunately, the present construction of most MR imaging systems makes direct visualization of the patient difficult, if not impossible. Furthermore, the static and time-varying magnetic (and electric) fields associated with MR imaging systems may be incompatible with most physiologic monitoring devices, either because of safety or function. The authors review herein the data regarding presently available monitoring devices for various physiologic parameters and provide recommendations regarding what--and whom--to monitor during clinical MR examinations. PMID- 1438734 TI - Modern concepts of brain motion and cerebrospinal fluid flow. PMID- 1438735 TI - Self-referral for diagnostic imaging. PMID- 1438736 TI - Closed-loop and strangulating obstruction of the small intestine: a new twist. PMID- 1438737 TI - The role of the radiologist in long-term central-vein access. PMID- 1438738 TI - Core breast biopsy, research, and what not to do. PMID- 1438739 TI - When is core biopsy really core? PMID- 1438740 TI - Brain parenchyma motion: measurement with cine echo-planar MR imaging. AB - With echo-planar magnetic resonance (MR) imaging, the authors measured the intrinsic pulsatile motion of brain parenchyma. Phase-sensitive, electrocardiography-gated, two-dimensional cine images were acquired throughout the cardiac cycle by using a spin-echo, blipped echo-planar MR pulse sequence. Transverse and coronal planes were obtained in 14 healthy volunteers. Corrections were made for gross head motion. Brain motion consisted of a rapid displacement in systole, with a slow diastolic recovery. The motion occurred chiefly in the cephalocaudal and lateral directions; the anteroposterior motions were relatively small. Cephalocaudal velocities increase with proximity to the foramen magnum. The lateral motion is mainly a compressive motion of the thalami. Brain parenchymal velocities were as high as 2 mm/sec caudally in the brain stem and 1.5 mm/sec medially in the thalami. Net parenchymal excursions were at most 0.5 mm. Phase-based echo-planar velocity measurements agreed well with echo-planar Fourier velocity zeugmatography measurements and were consistent with reported values. Velocity mapping with echo-planar imaging offers a rapid and flexible method of assessing the pulsation velocities of the human brain. PMID- 1438741 TI - Brain motion: measurement with phase-contrast MR imaging. AB - Brain motion during the cardiac cycle was measured prospectively in 10 healthy volunteers by using a phase-contrast cine magnetic resonance (MR) pulse sequence. The major cerebral lobes, diencephalon, brain stem, cerebellum, cerebellar tonsils, and spinal cord were studied. The overall pattern of brain motion showed caudal motion of the central structures (diencephalon, brain stem, and cerebellar tonsils) shortly after carotid systole, with concurrent cephalic motion of the major cerebral lobes and posterior cerebellar hemisphere. Peak brain displacement was in the range of 0.1-0.5 mm for all the structures except the cerebellar tonsils, which had greater displacement (0.4 mm +/- 0.16 [mean +/- standard error of mean]). Caudal motion of the central structures did not occur simultaneously but progressed in a caudal-to-rostral and posterior-to-anterior sequence, being seen first in the cerebellar tonsils and then later in the diencephalon (hypothalamus). Caudal motion of the low brain stem and cerebellar tonsil was simultaneous with caudal motion of cerebrospinal fluid in the cervical subarachnoid space. Oscillatory flow in the aqueduct was delayed compared with brain stem motion. PMID- 1438742 TI - Intracerebral lesion contrast with spin-echo and fast spin-echo pulse sequences. AB - Fast spin-echo (FSE) magnetic resonance (MR) imaging was compared with conventional, peripherally gated T2-weighted spin-echo (SE) imaging in the detection of high- and low-signal-intensity lesions in the central nervous system. Lesion detectability was determined with percentage of contrast measurements and contrast-to-noise ratios with two different measurements for noise. All three measures of lesion detectability were similar. FSE and SE sequences were quantitatively equivalent in the detection of high-signal intensity lesions. The SE sequence, however, was superior to the FSE sequence in the detection of small, low-signal-intensity lesions in the central nervous system caused by magnetic susceptibility effects. PMID- 1438743 TI - Intracranial vascular stenosis and occlusion: evaluation with three-dimensional time-of-flight MR angiography. AB - To assess the usefulness of magnetic resonance (MR) angiography in the characterization of intracranial arterial stenosis and occlusion, a three dimensional time-of-flight method was compared with conventional angiography in 214 vessels in 29 patients. Studies were independently interpreted by two neuroradiologists who scored each vessel as normal, narrowed, or occluded. Overall, 97% of normal vessels and 100% of occlusions were correctly graded. Sixty-one percent of stenoses were graded correctly; the remainder were graded as normal. The portions of the intracranial vessels near the skull base and especially the paracavernous and supraclinoid segments of the internal carotid arteries were areas of frequent over- and underestimation of stenosis due to the presence of dephasing artifacts. In patients with stenosis or occlusion, MR angiography also provided information regarding the presence of collateral flow in the circle of Willis. When used in conjunction with MR imaging of the brain and MR angiography of the extracranial carotid arteries, intracranial MR angiography allows a more complete evaluation of the patient with symptoms of cerebral ischemia or infarction. PMID- 1438744 TI - Mapping of brain tumor metabolites with proton MR spectroscopic imaging: clinical relevance. AB - Brain tumor metabolism was studied with hydrogen-1 magnetic resonance spectroscopy and positron emission tomography with fluorine-18 fluorodeoxyglucose in 50 patients. N-acetylaspartate (NAA) was generally decreased in tumors and radiation necrosis but was somewhat preserved at neoplasm margins. Choline was increased in most solid tumors. Solid high-grade gliomas had higher normalized choline values than did solid low-grade gliomas (P < .02), but the normalized choline value was not a discriminator of tumor grade, since necrotic high-grade lesions had reduced choline values. Serial studies in one case showed an increase in choline as the glioma underwent malignant degeneration. Choline values were lower in chronic radiation necrosis than in solid anaplastic tumors (P < .001). In two cases studied before and after treatment, clinical improvement and a reduction in choline followed therapy. Lactate is more likely to be found in high grade gliomas, but its presence is not a reliable indicator of malignancy. PMID- 1438745 TI - Cytotoxic brain edema: assessment with diffusion-weighted MR imaging. AB - To determine whether cytotoxic brain edema is associated with a decrease in diffusion, it was induced in rats, in the absence of ischemia, with an established model of acute hyponatremic encephalopathy. Cytotoxic brain edema secondary to acute hyponatremia was induced with intraperitoneal injections of 2.5% dextrose in water and subcutaneous injection of arginine-vasopressin. Coronal spin-echo magnetic resonance (MR) images were obtained with and without strong diffusion-sensitizing gradients before and after induction of acute hyponatremia. The apparent diffusion coefficient (ADC) was measured at two coronal section locations. In hyponatremic rats, the brain ADC was significantly reduced (P = .0153 and .0001) and was positively correlated with increased total brain water content (P = .0011). Plots of ADC versus total brain water showed a statistically significant inverse linear relationship between ADC and increasing brain water at the anterior coronal section location. The results indicate that the ADC may be a sensitive indicator of cytotoxic brain edema and thus may enable quantitative evaluation of such edema with diffusion-weighted MR imaging. PMID- 1438746 TI - Malignant parotid tumors: clinical use of MR imaging and histologic correlation. AB - Magnetic resonance (MR) imaging was performed in 116 patients in whom a parotid mass lesion was clinically suspected. Eighty-six patients had benign disease. The 30 patients in whom a malignant tumor was found were further evaluated. To determine which features are characteristic of malignant parotid tumors, spin echo T1- and T2-weighted images of malignant lesions in the parotid gland were compared with those of benign disease. In our series, tumor margins, homogeneity, or signal intensity were not discriminative factors to correctly predict benign or malignant disease. Infiltration into deep structures (eg, the parapharyngeal space, muscles, and bone) was observed only in malignant tumors. Infiltration into subcutaneous fat was noticed in malignant as well as in inflammatory disease. No statistically significant correlation was found between tumor grade and MR imaging features in malignant disease. MR imaging is useful in delineating malignant tumors but is unreliable in correctly predicting the histologic nature of a mass lesion in the parotid gland. PMID- 1438747 TI - Increased corneal temperature caused by MR imaging of the eye with a dedicated local coil. AB - To determine the existence of tissue heating-associated risks to the eye with magnetic resonance (MR) imaging performed at high specific absorption rates (SARs), corneal temperature was measured in 14 patients immediately before and after MR imaging performed with a 1.5-T, 64-MHz unit and a quadrature-driven body coil for radio-frequency transmission and a receive-only local coil designed for eye imaging. Fast spin-echo pulse sequences were used predominantly. Estimated peak SARs ranged from 3.3 to 8.4 W/kg. A statistically significant (P < .001) increase in average corneal temperature (32.2 degrees C +/- 0.7 before imaging, 33.1 degrees C +/- 0.6 after) was associated with MR imaging of the eye. The changes in corneal temperature ranged from 0.2 degrees to 1.8 degrees C (average, 0.9 degrees C). The highest corneal temperature measured after MR imaging was 35.1 degrees C. MR imaging performed with a dedicated local coil at the SARs studied produced elevations in corneal temperature that were physiologically inconsequential and below the temperature threshold (41 degrees to 55 degrees C) for radio-frequency radiation-induced cataractogenesis. PMID- 1438748 TI - Disparities in reimbursement to radiologists and nonradiologists for 65 common outpatient imaging studies. AB - The authors examined global charges (incorporating both technical and professional components) and global reimbursement allowances for all radiographic and ultrasound (US) examinations performed on Pennsylvania Blue Shield subscribers in the Lehigh Valley area of Pennsylvania during 1990. Data for radiologists and nonradiologists were compared with respect to all procedure codes for which at least 25 claims were submitted, yielding a sample of 40,619 radiographic examinations (54 procedure codes) and 9,761 US examinations (11 procedure codes). Radiologists' mean charges were higher than those of nonradiologists for 38 of the 54 radiographic codes. However, nonradiologists received higher mean reimbursement allowances for 39 of the 54 codes. Among the 11 US codes, nonradiologists' mean charges were higher for 10 and they received higher mean reimbursement allowances for seven. The averages of the mean reimbursement allowances for individual codes were higher for nonradiologists in both the radiographic and US categories. Pennsylvania Blue Shield has begun steps to eliminate disparities in reimbursements to providers who submit claims for imaging examinations. PMID- 1438749 TI - Mammographic features of 455 invasive lobular carcinomas. AB - Of 6,009 cases of breast cancer studied, 455 (7.6%) were invasive lobular carcinoma (ILC); 341 of these (75%) were pure ILC and 114 (25%) were ILC mixed with ductal forms. The mammographic features were compared with those of the 5,554 other breast carcinomas. Pure ILCs were less frequently round (1% vs 11%) and more frequently spicular (28% vs 23%) or with architectural distortion (18% vs 6%) than the other breast carcinomas. Microcalcifications were less common (24% vs 41%) and retraction of the skin (25% vs 21%) and nipple (26% vs 17%) was more common in pure ILC than in the other breast carcinomas. When complementary magnification views were obtained, only 50% were helpful in diagnosis of ILC while 75% were helpful in diagnosis of other breast carcinomas. Malignancy was less frequently diagnosed in ILC (57%) than in the other breast carcinomas (64%). The results were intermediate in the mixed ILC group. PMID- 1438750 TI - Effects of fine-needle aspiration on the US appearance of the breast. AB - Fine-needle aspiration (FNA) of normal breast tissue or benign lesions can cause changes that suggest malignancy at ultrasound (US) examination. Serial US studies showed that three of 17 patients developed signs mimicking malignancy following FNA of palpable breast lumps. A second group of 14 patients had US signs of malignancy in palpable lumps following recent FNA. Nine patients with benign lesions were unnecessarily worried, since the appearance was probably due to FNA. Diagnosis of malignancy was delayed in one of five patients because the US appearance was attributed to the FNA in the presence of false-negative cytologic findings. FNA of normal breast tissue or benign masses produced tissue changes in 18% of cases that altered the US appearance from normal or benign to possibly malignant. The changes took up to 4 months to subside. If US is clinically indicated, it should be performed before FNA. PMID- 1438751 TI - Shifting pneumothorax after heart-lung transplantation. AB - Heart-lung transplantation involves the total replacement of two of the most complex organs of the thoracic cavity. This procedure is usually reserved for patients with failure of both systems, such as in primary pulmonary hypertension or chronic Eisenmenger physiology. The en bloc replacement of the heart and lungs leaves an open communication between the two sides of the thorax that may allow air or fluid to shift from one side to the other. To evaluate this possibility, the authors reviewed the chest radiographs of 25 heart-lung transplant recipients for signs of rapidly changing pneumothoraces that could not be explained by the conventional dynamics of pleural physiology. A series of postoperative radiographs showed unusual shifting or apparently rapid disappearance of pneumothoraces in eight patients. Decompression of a pneumothorax with a contralateral chest tube was a phenomenon observed in six of these patients. PMID- 1438752 TI - AMBER and conventional chest radiography: comparison of radiation dose and image quality. AB - The authors compared the radiation dose to the patient and the image quality in advanced multiple-beam equalization radiography (AMBER) with those in conventional chest radiography. Organ doses were estimated for an anthropomorphic phantom from measurements with thermoluminescence dosimeters. These measurements were supplemented with area-air kerma products obtained during chest examinations of 223 patients. Image quality was determined by means of a contrast-detail image evaluation test. An improvement in image quality in regions of high absorption and an increased dose to the patient were found for the AMBER technique compared with the conventional technique. However, for both techniques, the radiation exposure was relatively low compared with other reported values of patient dose during chest radiography. The estimated effective dose for an average-size patient during chest radiography with posteroanterior and lateral projections is 0.085 mSv for the conventional and 0.14 mSv for the AMBER technique. PMID- 1438753 TI - Junctional parenchyma: revised definition of hypertrophic column of Bertin. AB - The so-called hypertrophic column of Bertin is a normal variation and simply represents unresorbed polar parenchyma of one or both of the two subkidneys that fuse to form a normal kidney. It contains renal cortex, pyramids, and columns (septa) of Bertin. (Since all elements of the tissue are normal, that is, neither hypertrophic nor a displaced or embryonic rest, it is referred to as "junctional parenchyma.") When a masslike lesion is suspected at sonography or excretory urography, diagnosis of junctional parenchyma can be made with a high degree of certainty when sonography shows that the structure (a) is located between the overlapping portion of two renal sinus systems, (b) is bordered by a junctional parenchymal line and defect, (c) contains renal cortex, pyramids, and columns of Bertin, and (d) contains renal cortex that is continuous with the adjacent renal cortex of the same subkidney. PMID- 1438754 TI - Testicular tumors: findings with color Doppler US. AB - A study of 28 patients with surgically proved testicular tumors was performed to determine the appearance at color Doppler ultrasound (US) scanning. There was a general correlation of tumor size and vascularity. Twenty of 21 (95%) tumors larger than 1.6 cm were hypervascular. Six of seven (86%) tumors smaller than 1.6 cm were hypovascular. One small, 1.1-cm-diameter seminoma was hypervascular, and one 2.8-cm-diameter seminoma was hypovascular. The histologic findings of the tumor did not correlate with the vascularity of the lesion as seen at color Doppler US. Resistive indexes ranged from .476 to 1.0 (mean, 0.70). Peak systolic velocities ranged from 8.4 cm/sec to 64.9 cm/sec (mean, 9.8 cm/sec). Venous flow was detected in eight tumors. The gray-scale findings, as well as history and physical examination findings, correctly suggested a neoplasm in all cases. The findings at color Doppler US were prospectively interpreted as indicative of neoplasm in 27 cases and as indicative of inflammation in one case. The authors conclude that color Doppler US scanning has only a limited role in the evaluation of testicular tumors. PMID- 1438755 TI - Renal US findings in sulfadiazine-induced crystalluria. AB - The authors report two cases of sulfadiazine-induced obstructive nephropathy that were diagnosed with ultrasound (US). Renal US demonstrated layered clusters of echogenic shadowing material--presumed to be sulfa crystals--which cleared when the crystalluria resolved. The authors conclude that renal US is helpful in diagnosing sulfa calculi and subsequent obstructive nephropathy. PMID- 1438756 TI - Bladder tumor staging: comparison of conventional and gadolinium-enhanced dynamic MR imaging and CT. AB - With computed tomography (CT) and unenhanced magnetic resonance (MR) imaging, stage pT3b extravesical extension and beyond can be diagnosed, but tumors confined to the bladder wall (stages pT1-pT3a) are poorly delineated. To determine whether visualization of such tumors could be improved with gadolinium enhanced MR imaging, dynamic breath-hold T1-weighted MR images were obtained after intravenous infusion of 0.1 mmol/kg gadopentetate dimeglumine in 79 patients (86 tumors). Conventional MR images, CT scans, and histologic correlation were available in all cases. With dynamic gadolinium-enhanced MR imaging, the mucosa could be distinguished from the muscular layers of the bladder wall. Staging accuracy with this technique was 85% (73 of 86), which was significantly better than with CT (55%; 47 of 86) (P < .005) or conventional MR imaging (58%; 50 of 86) (P < .05). The accuracy of staging the intramural extent (pT1-pT3a) of bladder tumors was thus improved with gadolinium-enhanced dynamic MR imaging. PMID- 1438757 TI - Dandy-Walker variant: prenatal sonographic features and clinical outcome. AB - The Dandy-Walker variant is a less severe posterior fossa anomaly than the classic Dandy-Walker malformation. In 17 consecutive fetuses, the Dandy-Walker variant was diagnosed at sonography, and associated defects, karyotypic anomalies, and outcomes were evaluated. Four of the 17 fetuses (24%) had mild ventriculomegaly. Eight of the 17 (47%) had concurrent non-central nervous system (CNS) anomalies. Five fetuses (29%) had an abnormal karyotype (two with trisomy 18, one each with trisomy 13, 21, and 11q+) and associated sonographic anomalies. Six of the 17 fetuses (35%) died in utero or during the neonatal period, two are severely handicapped, and the other nine are developing normally at ages 4 months to 4 years. Six of the nine normally developing infants (53%) lacked non-CNS sonographic findings. Because the prognosis is uncertain for an infant born with the prenatal diagnosis of Dandy-Walker variant, prenatal recognition of the anomaly allows for the option of fetal karyotyping and for arrangement for postnatal follow-up. PMID- 1438758 TI - Twin pregnancies: accuracy of first-trimester abdominal US in predicting chorionicity and amnionicity. AB - A first-trimester transabdominal ultrasound (US) study was performed on twin pregnancies to determine the utility of US in predicting chorionicity and amnionicity. Among 85 dichorionic-diamniotic (DC-DA) twin pairs, a thick membrane was present in 78 (92%). Four of the DC-DA cases without a thick membrane had two distinct placental sites, allowing 82 DC-DA pregnancies (96%) to be predicted. Among 16 monochorionic-diamniotic (MC-DA) twin pairs, a thin membrane was present in 14 (88%). None of the four monochorionic-monoamniotic (MC-MA) cases had an identifiable membrane. The lambda sign had no value in this evaluation and was actually misleading, while a thick membrane or the identification of two separate placentas was always predictive of DC-DA twinning. However, a thin membrane, while usually predictive of an MC-DA pregnancy, did not exclude a DC-DA gestation. When no membrane is present, an MC-MA gestation is probable; however, a diamniotic pregnancy may still be present, and further evaluation is suggested. PMID- 1438759 TI - Effect of scanning pressure on intracranial hemodynamics during transfontanellar duplex US. AB - The purpose of this study was to determine the effect of transducer scanning pressure during duplex ultrasonographic evaluation of intracranial hemodynamics in newborns. Doppler spectra were obtained from the anterior cerebral artery with use of light and firm scanning pressure over the anterior fontanelle in 23 healthy infants and 20 infants with reduced cranial compliance due to ventricular dilatation, intracranial hemorrhage, diffuse cerebral edema, and extraaxial fluid. In healthy infants, the mean resistive index (RI) increased from 69.9 +/- 3 to 74.8 +/- 3 (P < .005), and mean time average velocity (TAV) decreased from 11.1 cm/sec +/- 1.3 to 8.6 cm/sec +/- 1.3 (P < .0001) with firm scanning pressure. In infants with decreased cranial compliance, mean RI increased from 67.8 +/- 4 to 85 +/- 5, and mean TAV decreased from 16.3 cm/sec +/- 2 to 10.7 cm/sec +/- 2 (P < .0001 for both comparisons). A significant alteration in RI with firm technique (> or = 20% increase in RI, or reversal of diastolic flow) was observed in 12 of 28 examinations in infants with decreased cranial compliance and in only one of 23 healthy infants (P < .005). These data show that scanning pressures during duplex ultrasonography can significantly affect intracranial hemodynamics, especially in infants with altered cranial compliance. PMID- 1438760 TI - Urethral stones: US for identification in boys with hematuria and dysuria. AB - There are multiple causes for hematuria in infants and children. When hematuria is accompanied by dysuria, however, one should focus attention on the lower urinary tract. Although ultrasound (US) is a well-established method for assessing the kidneys and bladder, little attention has been focused on its use for evaluating urethral abnormalities, since voiding cystourethrography or retrograde urethrography usually is used. In the cases of two young boys, sonography aided in the identification of clinically unsuspected urethral stones. US evaluation of the urethra is now included as an integral part of urinary tract sonography in male patients with hematuria accompanied by dysuria. PMID- 1438761 TI - Closed-loop and strangulating intestinal obstruction: CT signs. AB - In 19 patients with closed-loop intestinal obstruction, including 16 patients with strangulating obstruction, the findings at examination with computed tomography (CT) were retrospectively correlated with the surgical and pathologic findings and evaluated by two radiologists. Signs of closed-loop obstruction, present in 15 patients, were associated with the configuration of the incarcerated loop of small bowel, abnormalities detected at the site of obstruction, or both. These abnormalities were the following: a U-shaped, distended, fluid-filled bowel loop; the whirl sign; the beak sign; a triangular loop; two adjacent collapsed loops of bowel at the site of obstruction; or all of these. CT signs of strangulation, seen in 10 of the 16 patients with ischemic or infarcted bowel, were associated with the appearance of the bowel wall (thickening, high attenuation, and the target sign), abnormalities in the attached mesentery, or both. In mechanical obstruction of the small bowel, detection of ischemic changes in the bowel wall or mesentery with CT indicates strangulation. Absence of CT findings of ischemia or infarction does not rule out strangulation. PMID- 1438762 TI - High-attenuation lymphadenopathy in AIDS patients: significance of findings at CT. AB - A retrospective evaluation was performed of the location and attenuation characteristics of abdominal and pelvic lymphadenopathy, identified at dynamic sequential bolus computed tomography (CT) in 69 patients with acquired immunodeficiency syndrome (AIDS). Lymph node appearance at CT was characterized as hyperattenuating, isoattenuating, or hypoattenuating relative to the iliopsoas muscle. The significance of finding hyperattenuating adenopathy in the patient population was evaluated. Thirty-three patients had hyperattenuating adenopathy, including 26 with the epidemic form of Kaposi sarcoma (KS). Of 38 patients with epidemic KS, 26 had hyperattenuating, 11 had isoattenuating, and one had hypoattenuating lymphadenopathy. The positive predictive value of hyperattenuating adenopathy for epidemic KS was 79%. These findings were statistically significant at the 95% confidence interval (P < .005). Hyperattenuating lymphadenopathy, identified on dynamic sequential bolus CT scans in AIDS patients, was seen with disseminated KS in approximately 80% of cases. PMID- 1438763 TI - Cellulose as a gastrointestinal US contrast agent. AB - Ultrasound (US) imaging of the abdomen often is compromised by artifacts due to adjacent bowel gas. In an attempt to decrease gas artifacts and improve US image quality, the authors evaluated the use of cellulose preparations as gastrointestinal US contrast agents. Optimal homogeneity and reflectivity were evaluated in phantom solutions, and two suitable agents were selected for clinical trial. Ten volunteers underwent abdominal US imaging before and after contrast agent administration on three separate occasions. The volunteers drank 800 mL of freshly degassed water and two different gastrointestinal US contrast agents. US images obtained before and after administration of contrast material were evaluated by five radiologists and scored for bowel marking, visualization of abdominal anatomy, and image degradation by bowel gas. Compared with water, the orally administered US contrast agents improved visualization of bowel and abdominal anatomy, with diminished gas artifact. PMID- 1438764 TI - Intestinal anisakiasis: US in diagnosis. AB - Eighteen consecutive patients with intestinal anisakiasis were studied with high resolution ultrasound (US) and barium studies. US showed markedly thickened bowel loops associated with luminal narrowing, swelling of Kerckring folds, and decreased peristalsis. A small amount of ascitic fluid around the bowel loops was found, and cytologic examinations of the ascites revealed a dense infiltration of eosinophils. Barium studies demonstrated segmental mucosal edema of the small intestine: The most common site was the distal ileum, and the mean length of the edematous lesion was 19 cm. All patients underwent treatment of symptoms without laparotomy, and their symptoms disappeared by the eighth day after onset. Patients with acute abdominal symptoms should be asked about the intake of raw or undercooked fish. If the above US features are found, the diagnosis of intestinal anisakiasis must be seriously considered to avoid unnecessary surgical treatment. PMID- 1438765 TI - Evaluation of myocardial perfusion abnormalities with gadolinium-enhanced snapshot MR imaging in humans. Work in progress. AB - To determine whether myocardial perfusion abnormalities could be detected in patients with coronary artery disease by means of contrast material-enhanced magnetic resonance (MR) images, a snapshot imaging technique was used in six patients with coronary artery disease and four healthy subjects in conjunction with pharmacologic stress (dipyridamole infusion) and bolus injection of gadopentetate dimeglumine. MR images from all patients and healthy subjects were quantitatively analyzed to define spatial changes in signal intensity after administration of dipyridamole and gadopentetate dimeglumine. The resultant findings were compared with findings on thallium-201 scintigrams obtained after administration of dipyridamole and on coronary arteriograms in all patients. Nine myocardial regions supplied by stenosed arteries showed diminished levels of signal intensity after infusion of the contrast agent compared with those of normally perfused regions. These findings were in agreement with those obtained with T1-201 scintigraphy (in eight of nine regions) and arteriography. Thus, contrast-enhanced high-speed MR imaging with use of dipyridamole enabled detection of regional perfusion abnormalities in humans. PMID- 1438766 TI - The Groshong catheter: initial experience and early results of imaging-guided placement. AB - Fifty Groshong catheters were placed in 50 patients with use of ultrasound (US) and fluoroscopic guidance in the radiology suite: 49 were placed via the subclavian vein and one was placed via the left internal jugular vein. All (100%) attempts at catheter placement were successful. Imaging guidance affected the placement of catheters in 12 cases (24%), including four patients (8%) in whom vascular access would not have been possible with blinded percutaneous venipuncture or surgical cutdown. After a four-case learning curve period, during which one pneumothorax (2%) and two arterial punctures (4%) occurred, there were no further venipuncture-related complications. One catheter was removed because of infection (2%) and one because of allergic reaction (2%) to the antimicrobial cuff. Four patients with cutaneous infections and one with catheter-related sepsis were successfully treated with antibiotics. Results demonstrate the initial promise of imaging-guided placement of central venous access catheters when performed in the radiology suite. PMID- 1438767 TI - Arterial and venous blood flow: noninvasive quantitation with MR imaging. AB - Quantitative measurements of arterial and venous blood flow were obtained with phase-contrast cine magnetic resonance (MR) imaging and compared with such measurements obtained by means of implanted ultrasound (US) blood flow probes in anesthetized dogs. The US flowmeter was enabled during a portion of each MR imaging sequence to allow virtually simultaneous data acquisition with the two techniques. MR imaging data were gated by means of electrocardiography and divided into 16 phases per cardiac cycle. The rates of portal venous blood flow measured with MR imaging and averaged across the cardiac cycle (710 mL/min +/- 230 [standard deviation]) correlated well with those measured with the flowmeter and averaged in like fashion (751 mL/min +/- 238) (r = .995, slope = 1.053). The correspondence in arterial blood flow was almost as good. No statistically significant difference existed between the paired measurements of blood flow obtained with MR imaging and the implanted probe. It is concluded that, as a noninvasive means of accurate quantification of blood flow, phase-contrast MR imaging may be especially useful in deep blood vessels in humans. PMID- 1438768 TI - Role of parallel transjugular intrahepatic portosystemic shunts in patients with persistent portal hypertension. AB - Transjugular intrahepatic portosystemic shunts (TIPS) were placed in 93 patients between June 1990 and January 1992 for treatment of variceal hemorrhage. In each case, a Wallstent (Schneider USA, Minneapolis) was used to support the hepatic parenchymal tract between the hepatic and portal veins. Currently, these stents have a maximal diameter of 10 mm. In eight of 93 patients, major portal hypertension persisted after placement of a 10-mm-diameter shunt, manifested by continued rapid variceal filling and elevated portosystemic gradients. A second TIPS was placed parallel to the first in these patients to allow further portal decompression. In two other patients, a second TIPS was placed because the initial shunt functioned suboptimally. The mean postprocedural portosystemic gradient in the patients who received one TIPS was 10.2 mm Hg +/- 3.7. In patients who received two TIPS, the mean postprocedural gradient was 19.1 mm Hg +/- 3.8 after placement of the first TIPS and 12.5 mm Hg +/- 3.5 after placement of the second. Two patients developed their first episode of encephalopathy after placement of two TIPS. The methods and indications for placing two TIPS in this select population are discussed. PMID- 1438769 TI - Fine-needle aspiration biopsy for cytopathologic analysis: utility of syringe handles, automated guns, and the nonsuction method. AB - The performances of seven techniques and devices used with 22-gauge needles to obtain biopsy specimens for cytologic analysis were compared by means of single blinded evaluation with an objective, previously published grading scheme. A total of 420 specimens were obtained from 10 fresh human cadavers (42 specimens per cadaver), including 30 hepatic, 20 renal, and 10 pancreatic specimens per technique or device. No statistical differences existed in the liver, kidney, or pancreas or in the combined data in the performance of the aspirator gun, syringe holders, vacuum needle, and end-cut gun versus the manual aspiration biopsy technique performed with a 22-gauge Chiba needle. However, nonaspiration, fine needle capillary biopsy (FNCB) performed statistically significantly worse than any other technique or device in the kidney and pancreas and in comparison with the overall combined data. In the liver, no statistically significant difference existed in the overall performance of FNCB versus conventional aspiration biopsy, but the amount of cellular material obtained with FNCB was statistically significantly less. PMID- 1438770 TI - Deep pelvic abscesses: transrectal drainage with radiologic guidance. AB - Transrectal catheter drainage was performed under radiologic guidance in eight patients with deep pelvic abscesses during a 7-month period. One patient underwent two procedures. In five patients, the abscess could not be palpated at rectal examination. Seven procedures were performed with fluoroscopic guidance. Transrectal ultrasound was performed in conjunction with fluoroscopy for two procedures. Medium to large (8-14-F) locking catheters were used in seven procedures, and small (5-F) nonlocking pigtail catheters were used in two. The catheter was left in place for 3 days or less in all but one patient, in whom the catheter was left in place for 20 days. Five abscesses were drained through the anterior or anterolateral rectal wall and four, including one repeat drainage, through the posterior rectal wall. No complications occurred as a direct result of transrectal drainage. Successful initial drainage was established with clinical improvement in all cases. Two patients eventually required surgery, one for continued bleeding into an infected hematoma and one for abscess recurrence after tube dislodgment. Transrectal drainage performed with radiologic guidance is a safe, feasible procedure; is well tolerated by patients; and is relatively easy to perform with the techniques described. PMID- 1438771 TI - Percutaneous recanalization of a renal artery in aortic dissection. AB - Chronic renal failure acutely worsened in a patient with a type B aortic dissection. Aortography revealed an occlusion of the left renal artery without renal intimal tear. Percutaneous recanalization, performed with a self-expandable stent, resulted in improvement in the renal function. This technique offers a new therapeutic choice in patients with visceral complications of aortic dissection. PMID- 1438772 TI - Multiple myeloma: spinal MR imaging in patients with untreated newly diagnosed disease. AB - Spinal magnetic resonance (MR) imaging was performed in 29 patients with newly diagnosed, untreated multiple myeloma. Nineteen (66%) patients were asymptomatic. Sagittal pre- and postcontrast T1-weighted spin-echo images and gradient-recalled echo images of the thoracic and lumbosacral spine were obtained. Marrow involvement was identified in 20 (69%) patients. There were three MR patterns: focal lesions in nine patients (31%), diffuse involvement in seven (24%), and an inhomogeneous pattern of tiny lesions on a background of normal marrow in four (14%). A statistically significant correlation between MR imaging patterns of marrow involvement and serum hemoglobin values (one-way, P = .0899; Kruskal Wallis, P = .0620) and between MR imaging patterns and percentage of marrow plasmacytosis (Kruskal-Wallis, P = .0314) was noted, with patterns of diffuse and focal marrow involvement associated with more abnormal values. Spinal MR imaging in patients with early myeloma may reveal marrow involvement in both symptomatic and asymptomatic patients. Some correlation was found between MR imaging patterns and laboratory indexes of disease. PMID- 1438773 TI - Quantitative imaging of Gaucher disease. AB - Twenty-three patients with type 1 Gaucher disease were evaluated with a battery of quantitative imaging techniques. Plain radiographs were used to measure cortical thickness and Erlenmeyer flask deformity. Xenon-133 uptake was measured in scans of the lower extremities. Dual-energy quantitative computed tomography was used for calculation of trabecular bone and bone marrow fat content in the spine and long bones. Magnetic resonance (MR) imaging was performed to evaluate disease extent and three-dimensional splenic volume. MR images were also used to provide quantitative measurements of each vertebral fat fraction. Each imaging modality was correlated with the others as well as with the clinical history of skeletal complications and the hematocrit and acid phosphatase activity. There was a strong relationship between splenic volume and disease severity as measured clinically and with laboratory testing. The spinal fat fraction also correlated with these measures of disease severity and with the femoral fat fraction and xenon uptake. No measurement allowed discrimination of patients with from those without skeletal complications. PMID- 1438774 TI - Hill-Sachs lesion: comparison of detection with MR imaging, radiography, and arthroscopy. AB - Magnetic resonance (MR) imaging has proved to be a valuable method for documenting Hill-Sachs lesions. The authors retrospectively analyzed the diagnostic interpretations at plain film radiography, arthroscopy, and MR imaging in 76 patients. The analysis revealed that neither radiography nor arthroscopy displayed the lesion with sufficient accuracy to represent a true standard of reference for the evaluation of MR imaging in the diagnosis of the Hill-Sachs lesion. The data from the diagnostic interpretations were analyzed in three ways, each of which revealed that findings at MR imaging were more helpful than findings at radiography and/or arthroscopy in the diagnosis of the Hill-Sachs lesion. When the agreement of findings in two or three methods was used to assign a final diagnosis, MR imaging resulted in sensitivity of 97%, specificity of 91%, and accuracy of 94% in the detection of Hill-Sachs lesions. PMID- 1438775 TI - Osgood-Schlatter lesion: fracture or tendinitis? Scintigraphic, CT, and MR imaging features. AB - To determine whether the Osgood-Schlatter lesion (OS) is produced by avulsion fracture or injury to the patellar tendon, all images obtained in 28 cases of OS in 20 patients (16 scintigrams, 34 computed tomographic [CT] scans, and 27 magnetic resonance [MR] images) were retrospectively analyzed. In 21 cases, imaging was performed before and after treatment; in 20 cases, relief from pain was complete at the time of repeat examination. In all patients (100%), abnormal size of the tendon, decreased attenuation, and increase in signal intensity were compatible with the CT and MR imaging appearance of tendinitis. Distended deep infrapatellar bursa was a frequent finding, particularly on MR studies. These abnormalities had partially disappeared at follow-up examination. An ossicle was seen in only nine of 28 cases (32%); in three of seven cases with follow-up, the ossicle remained nonunited to the tibial tuberosity on follow-up studies despite relief from symptoms. This implies that healing of fracture is not essential for relief from symptoms. These results strengthen the argument that in most cases of OS, insult to the tendon and associated soft tissues, rather than avulsion fracture, causes OS. PMID- 1438776 TI - Long patellar tendon: radiographic sign of patellofemoral pain syndrome--a prospective study. AB - The position of the patella was studied prospectively in both knees of 45 consecutive patients (21 male and 24 female patients aged 16-48 years who were competitive [n = 17] or recreational [n = 28] athletes) who had unilateral patellofemoral pain syndrome without symptoms or signs of patellar instability at initial examination. In each knee, standardized anteroposterior, lateral, and tangential radiographs were obtained and six indexes of patellar position (the ratio of the patellar tendon to the greatest diagonal length of the patella, sulcus angles, lateral patellofemoral angle, lateral patellar displacement, patellofemoral index, and knee angle) were measured. When healthy and affected knees were compared, high riding of the patella due to long patellar tendon (patella alta) was the only definite finding in the affected knees. The shape of the intercondylar sulcus and the mediolateral position of the patella were identical in both knees, providing no evidence for patellofemoral incongruence or lateral patellar tilt. Results of this study strongly suggest that idiopathic retropatellar pain is closely associated with patella alta. PMID- 1438777 TI - Comparison of helical and serial CT with regard to three-dimensional imaging of musculoskeletal anatomy. AB - To test the hypothesis that helical computed tomographic (CT) scans provide three dimensional images as good as or better than those provided by serial CT, two objects were used to study the effects of helical CT: an angled cylindrical bone phantom and a human cadaveric femur specimen with a simulated fracture 1 mm wide. Both objects were immersed in a water bath, and a series of helical and serial CT scans were obtained with various parameters. Volumetric rendering was applied to the resultant data sets to create three-dimensional images, which three radiologists reviewed in a blinded manner to rate their fidelity, accuracy, and diagnostic usefulness. As expected, the images obtained with thin collimation and small intersection spacing or slow table movement were considered superior. Helical and serial CT data acquired with similar parameters were similar in quality, but helical CT is approximately five times faster than serial CT; hence, it is possible to use thinner collimation and obtain more sectional data with helical CT. PMID- 1438778 TI - Temperature changes induced in human muscle by radio-frequency H-1 decoupling: measurement with an MR imaging diffusion technique. Work in progress. AB - To investigate temperature increases in tissues during magnetic resonance (MR) imaging or spectroscopy, the authors measured temperature changes in vitro and in vivo (leg of a volunteer) in a condition simulating hydrogen-1 decoupling in MR spectroscopy. Noninvasive measurements were obtained by using the temperature dependence of the translational diffusion coefficient of water. Temperature was measured at 0.5 T (86 MHz) by using a stimulated-echo sequence that included intense gradient pulses and a procedure reducing sensitivity to bulk tissue motion. Calibration curves of the diffusion coefficient against thermocouple measured temperature were obtained for a gelatin phantom and bovine muscle. Temperature changes were 5.3 degrees C +/- 0.5 at 2.5 cm from the coil in gelatin and 7.7 degrees C +/- 0.5 at 0.7 cm in bovine muscle. The temperature changed by 4.9 degrees C +/- 1.9 at 2.2 cm from the coil in the calf muscle of a volunteer. The H-1 decoupling protocol can be adapted (modifications in transmission power, duty cycle) to reduce heating effects to below safety recommendations. PMID- 1438779 TI - Proceedings of a National Cancer Institute workshop: MR spectroscopy and tumor cell biology. AB - In December 1991, the National Cancer Institute held a workshop to evaluate the role of magnetic resonance (MR) spectroscopy in human cancer biology. The clinical and basic cancer research issues requiring use of MR spectroscopy, the advantages and limitations of MR spectroscopy, and future directions in MR spectroscopy of cancer were discussed. Consensus-building panels were formed on the following four topics: cell membrane biochemistry, tumor therapeutic response or drug resistance, appropriate model systems, and potential clinical applications of MR spectroscopy. The workshop members concluded that large prospective clinical studies as well as in vivo animal and human studies to define prognostic variables should be performed, with correlation between MR spectroscopic results and biochemical and physiologic features. Studies of phospholipid metabolism, the pharmacokinetics of anticancer agents, and effects of new cancer treatments on the tumor vasculature and normal tissues are needed. PMID- 1438780 TI - Prostate cancer: arterial infusion chemotherapy and alteration of intrapelvic blood flow. AB - Twenty-one patients with prostate cancer underwent intermittent arterial infusion chemotherapy with an implanted reservoir and alteration of the intrapelvic blood flow. One internal iliac artery was embolized with steel coils so that the drugs would perfuse throughout the tumor through a single tube. Angiography performed after embolization showed distinct tumor vessels. Intensive radioisotope accumulation was demonstrated in the prostate gland at scintigraphy performed with technetium-99m macroaggregated albumin. Ten milligrams each of cisplatin and doxorubicin were injected once a week by means of puncture of the implanted reservoir. All patients had more than a 50% reduction in tumor size. The response rate to this treatment was good; six patients experienced complete response, and 13 had partial response. Two patients had progressive disease. With this technique, small doses of the anticancer agents reached the tumor in high concentrations. Results were good, with few side effects. PMID- 1438781 TI - Adjustable automated biopsy device. AB - The authors describe a device for soft-tissue core biopsy with core length of 3 19 mm. Excellent results were obtained in combination with a new needle design in a series of 119 renal biopsies in pediatric and adolescent patients. With ultrasound guidance and adjustment of the core length in relation to kidney size, renal biopsy in pediatric patients can be safely performed with this device. PMID- 1438782 TI - Impact of section doubling on MR angiography. AB - To improve the quality of projection angiograms generated from three-dimensional magnetic resonance (MR) angiography data, the authors applied voxel shifting to create intermediate sections ("section doubling") prior to maximum intensity projection. To date, the authors have processed MR angiography studies with and without section doubling in 20 cases. Section doubling resulted in improved vessel contrast and delineation of continuity (especially of small vessels) in all cases. PMID- 1438783 TI - Intraparenchymal anesthesia infiltration during transjugular intrahepatic portosystemic shunting. AB - The authors describe a technique for administration of anesthetic to the area of the transparenchymal tract during transjugular percutaneous transhepatic portosystemic shunting. Seven of the eight patients in whom the technique was used did not experience pain during balloon dilation of the tract, and one patient experienced only minimal pain. The technique allows good pain control in patients with severe liver failure and resultant inability of the liver to metabolize pharmaceuticals. PMID- 1438784 TI - Radiation-induced optic neuropathy: correlation of MR imaging and radiation dosimetry. AB - The authors performed topographic correlation of dosimetric measurements with contrast medium-enhanced magnetic resonance (MR) imaging signal aberration in two cases of radiation optic neuropathy. The region of pathologic contrast enhancement in the optic nerve and chiasm had received 55-62 Gy, which supports the theory that the risk of injury to the optic nerve and chiasm increases steeply with radiation doses above the tolerance level of 50-55 Gy. PMID- 1438785 TI - Complication rates of DSA and conventional film cerebral angiography. PMID- 1438786 TI - Balloon angioplasty versus surgery. PMID- 1438787 TI - Radiologists, communication, and resolution 5. PMID- 1438788 TI - US evaluation of renal colic. PMID- 1438789 TI - Principles and signal processing techniques of the high-resolution electrocardiogram. PMID- 1438791 TI - Effects of vasodilator therapy on survival in patients with chronic heart failure. PMID- 1438790 TI - Contributions of frequency analysis to the identification of the spectral, temporal, and spatial features in signal-averaged electrocardiograms that distinguish patients prone to sustained ventricular arrhythmias. PMID- 1438792 TI - Principles and clinical uses of diuretic therapy. PMID- 1438793 TI - Synthesis of hexadecylphosphocholine (miltefosine). PMID- 1438794 TI - Experimental therapeutic studies with miltefosine in rats and mice. PMID- 1438795 TI - Hexadecylphosphocholine in liposomal dispersions. PMID- 1438796 TI - Hexadecylphosphocholine and octadecyl-methyl-glycero-3-phosphocholine: a comparison of hemolytic activity, serum binding and tissue distribution. PMID- 1438797 TI - Comparison of the tissue distribution of hexadecylphosphocholine and erucylphosphocholine. PMID- 1438798 TI - Hexadecylphosphocholine in the topical treatment of skin metastases in breast cancer patients. PMID- 1438799 TI - Topical application of hexadecylphosphocholine in patients with cutaneous lymphomas. PMID- 1438801 TI - Cellular uptake and metabolic fate of hexadecylphosphocholine. PMID- 1438800 TI - Antitumoral activity of alkylphosphocholines and analogues in human leukemia cell lines. PMID- 1438802 TI - Morphological changes of adherent and nonadherent cells by treatment with hexadecylphosphocholine and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine observed by scanning electron microscopy. PMID- 1438803 TI - Effects of hexadecylphosphocholine on cellular function. PMID- 1438804 TI - Determination of alkylphosphocholines and of alkyl-glycero-phosphocholines in biological fluids and tissues. PMID- 1438805 TI - Early effects of hexadecylphosphocholine on gene expression in leukemia cell lines. PMID- 1438806 TI - Induction of tumor cell differentiation by alkylphosphocholines: a new approach for in vitro screening. PMID- 1438807 TI - Antitumor activity of alkylphosphocholines and analogues in methylnitrosourea induced rat mammary carcinomas. PMID- 1438808 TI - Marine oils as a source of omega-3 fatty acids in the diet: how to optimize the health benefits. AB - Marine oils are receiving increasing attention as a source of C 20 and C 22 carbon omega-3 polyenoic fatty acids. The provision of preformed EPA and DHA from marine oils has profound implications for health and disease. Their role as precursors for the synthesis of eicosanoids and docosanoids explains many of the multisystemic effects observed when they are administered. Furthermore under some physiologic conditions such as preterm birth the evidence suggests that C 18 omega-3 fatty acids are not sufficiently converted to DHA to allow for biochemical and functional normalcy, thus DHA may be considered a conditionally essential nutrient for normal eye and brain development. Under disease conditions EPA plays a major role in modifying the balance between omega-6 and omega-3 derived eicosanoids thus modulating related functions. The use of marine oils has some potential risks that can be circumvented by careful processing, storing and preserving the unsaturated fatty acids. Technological procedures based on chemical and physical separation of the unsaturated fatty acids has permitted the elaboration of concentrated EPA and DHA for clinical testing. The development of structured lipids has allowed the synthesis of novel forms of EPA and DHA delivery. Further uses of marine oil to optimize health and prevent disease are predicted based on recent knowledge and technological developments. PMID- 1438810 TI - [The frontiers of molecular virology]. PMID- 1438809 TI - Recent advances in methodology for analysis of phytate and inositol phosphates in foods. AB - This review summarises the methods available for the analysis of phytate and structurally related molecules, i.e., inositol polyphosphates. Phytate has been determined by colorimetry, low pressure ion exchange column chromatography, phosphorus-31 fourier transform nuclear magnetic resonance spectroscopy (31P FT NMR), near-infrared reflectance spectroscopy and high performance liquid chromatography (HPLC). Among these techniques anion exchange column chromatography and HPLC were shown to be best suited for separation of inositol phosphates. Since inositol phosphates do not have a characteristic absorption spectrum, their detection in HPLC analysis is limited to methods employing monitoring of refractive index, post column reaction products, conductivity or indirect detection although other detection methods may be feasible. As refractive index detection under isocratic eluent conditions is relatively easy to manipulate, anion-exchange HPLC methods using a low capacity column or ion pair HPLC methods are recommended for the analysis of inositol phosphates in nutritional studies. PMID- 1438811 TI - [Genome structure and gene products of parvoviruses]. PMID- 1438812 TI - [Genome structure of adenoviruses]. PMID- 1438813 TI - [The genome structure of herpesviruses]. PMID- 1438814 TI - [Processing of vaccinia genome terminal: initiation of DNA synthesis and concatemer resolution]. PMID- 1438815 TI - [The function and the structure of plant DNA virus genomes]. PMID- 1438816 TI - [The structure of DNA bacteriophage genome]. PMID- 1438817 TI - [Structure and function of the picornavirus genome]. PMID- 1438819 TI - [Structure and function of the influenza virus genome]. PMID- 1438818 TI - [Genetic structures of paramyxovirus and rhabdovirus]. PMID- 1438820 TI - [Gene structures of arenaviruses and bunyaviruses--ambisense RNA viruses]. PMID- 1438822 TI - [The genome structure of plant viruses with single-stranded positive sense RNA]. PMID- 1438821 TI - [Structure of retroviral genome]. PMID- 1438823 TI - [Genome structure of plant reoviruses]. PMID- 1438825 TI - [Structure of RNA coliphage genomes]. PMID- 1438824 TI - [Viruses and ambisense RNA genomes of tenuivirus]. PMID- 1438826 TI - [Genome structure of viroid]. PMID- 1438827 TI - [Morphology of genome and genome-protein complex of viruses]. PMID- 1438829 TI - [Replication and gene expression of hepatitis B virus]. PMID- 1438828 TI - [Regulation of DNA replication and gene expression of adenovirus]. PMID- 1438830 TI - [Replication and gene expression of bacteriophages T3 and T7 (or phages T3 and T7)]. PMID- 1438831 TI - [Replication and gene expression of T4 phage DNA]. PMID- 1438832 TI - [Replication and gene expression of lambda phage]. PMID- 1438833 TI - [Filamentous bacteriophage of E. coli]. PMID- 1438834 TI - [Protein-priming DNA replication of bacteriophages phi 29 and M2]. PMID- 1438835 TI - [Replication and gene expression of picornavirus RNA]. PMID- 1438836 TI - [Transcription and replication of paramyxoviruses]. PMID- 1438837 TI - [Transcription and replication of the influenza virus genome]. PMID- 1438838 TI - [Regulation of the replication of human retrovirus]. PMID- 1438839 TI - [Replication and gene expression of HIV--a question posed by HIV]. PMID- 1438840 TI - [Plant RNA virus--TMV replication]. PMID- 1438841 TI - [Gene expression and RNA replication of RNA coliphages]. PMID- 1438842 TI - [Gene expression using adenovirus vector]. PMID- 1438843 TI - [Improvement and application of vaccinia virus vector]. PMID- 1438844 TI - [A baculovirus expression vector]. PMID- 1438845 TI - [Development of expression vector using influenza virus]. PMID- 1438846 TI - [Genetic engineering of paramyxovirus and rhabdovirus]. PMID- 1438847 TI - [Plant virus vector and recombinant virus]. PMID- 1438848 TI - [Picornavirus receptor]. PMID- 1438849 TI - [Recognition of sialo-sugar chains by influenza virus]. PMID- 1438850 TI - [Penetration of paramyxoviruses and their receptors]. PMID- 1438851 TI - [Interaction of HIV envelope protein gp120 with receptor CD4]. PMID- 1438852 TI - [Protease-dependent tropism, a conceptually old but newly established mechanism of viral infection]. PMID- 1438853 TI - [Host range of influenza virus]. PMID- 1438855 TI - [Host factors affecting retrovirus replication]. PMID- 1438856 TI - [Host factors required for the replication of RNA phage genomes]. PMID- 1438857 TI - [Involvement of positive (IRF-1) and negative (IRF-2) transcription factors in the gene regulation of the type I interferon system]. PMID- 1438854 TI - [Host cell proteins involved in paramyxovirus transcription and replication]. PMID- 1438858 TI - [Structure and function of mouse Mx 1 protein]. PMID- 1438859 TI - [Mechanism of cellular transformation by DNA tumor viruses]. PMID- 1438861 TI - [Processing and T cell recognition of viral antigens]. PMID- 1438860 TI - [Cell transformation by retroviruses]. PMID- 1438862 TI - [Immune response to viral infection]. PMID- 1438863 TI - [Mutation of virus genome]. PMID- 1438864 TI - [Molecular evolution of viruses]. PMID- 1438865 TI - [Past and future of vaccine development]. PMID- 1438867 TI - [Plant virus, yesterday and today]. PMID- 1438866 TI - [A brief history of the research on human tumor viruses]. PMID- 1438868 TI - [Function of E. coli chromosomal protein HU]. PMID- 1438869 TI - [p53 tumor suppressor gene and its clinical significance]. PMID- 1438870 TI - [Man's place in nature and its evolutionary molecular biology]. PMID- 1438871 TI - [Mechanism of stabilization of proteins by additives in freezing]. PMID- 1438872 TI - [A mushroom lectin: structure and function of Aleuria aurantia lectin]. PMID- 1438873 TI - [Analysis of DNA in interphase nuclei by fluorescence in situ hybridization]. PMID- 1438874 TI - Release of arachidonic acid metabolites from isolated human alveolar type II cells. AB - Human alveolar type II cells are thought to play a role in the pathogenesis of lung injury. Patterns of mediator release of arachidonic acid metabolism by type II cells were therefore studied after challenge with calcium ionophore A23187, opsonized zymosan and hydrogen peroxide. A time- and concentration dependent release of cyclooxygenase products was observed, with release of PGE2 greater than 6-keto-PGF1 alpha greater than TxB2. Addition of glutathione or bicarbonate further increased the production of PGE2. N-ethylmaleimide, a sulfhydryl (SH) reactant, induced a dose-dependent increase in the release of TxB2 and 6-keto PGF1 alpha, but not of PGE2. This relates most likely to the SH-dependency and glutathione requirement of the PGE2 isomerase and SH-independence of thromboxane and prostacyclin isomerase. PMID- 1438875 TI - Lack of prostaglandin effect on sodium balance and hyperreninemia in adrenalectomized rats. AB - Glucocorticoids are known inhibitors of prostaglandin production. Prostaglandin E2 (PGE2) and prostacyclin (PGI2) are promoters of natriuresis and renin release. Excessive prostaglandin production, therefore, might contribute to the altered sodium balance and renin release observed in primary adrenal insufficiency. To test this hypothesis, sodium balance and prostaglandin production were measured in adrenalectomized rats and in animals receiving prostaglandin inhibitors or replacement dexamethasone. Compared to sham-operated controls, adrenalectomized rats had decreased two-day sodium balance and elevated plasma renin concentration (PRC), renal PGE2 production, and renal 6-ketoprostaglandin F1 alpha (6kPGF1 alpha, the nonenzymatic metabolite of PGI2); however, no appreciable change in aortic 6kPGF1 alpha production was observed. Dexamethasone given to adrenalectomized rats normalized PRC but had no effect on sodium balance or prostaglandin production. Likewise, prostaglandin inhibitors did not alter the sodium balance or decrease the PRC post adrenalectomy. These data confirm renal prostaglandin production is increased in adrenalectomized rats, but suggest that the elevation is not due directly to glucocorticoid deficiency. Further, PRC levels in adrenal insufficiency do not appear to be prostaglandin mediated. In conclusion, excessive renal prostaglandin production does not contribute to altered sodium balance or increased PRC in adrenalectomized rats. PMID- 1438876 TI - Fetal viability does not affect the onset of stretch-induced labor and the increase in amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels. AB - The role of the fetus in the onset and progress of stretch-induced labor and in the change in amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels was evaluated in six normal pregnant women (group 1) and six women whose fetuses had been dead for more than one week (group 2). The uterus was distended by a balloon inflated with physiologic saline. Regular uterine contractions occurred, and increased in all patients. Within 21 hours, all patients delivered a normal baby in group 1 and a macerated fetus in group 2. There was no significant difference in induction-delivery interval between the two groups. Both groups showed a significant and similar range of increases in the levels of amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite during treatment (P less than 0.001). Thus, the fetus has no functional role in the onset and progress of stretch-induced labor or in the rise of amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels. PMID- 1438877 TI - Incorporation of [14C] arachidonic acid into ovine conceptus and endometrial lipids. AB - The purpose of this study was to quantitate conceptus and endometrial incorporation of [14C]arachidonic acid (AA) into individual neutral and polar lipids. Endometrium and conceptuses from pregnant ewes and endometrium from nonbred ewes were collected 14 and 16 d after onset of estrus (d 0). Tissues were incubated for 8 h at 37 degrees C in medium containing 1 microCi of [14C]AA. Thin layer chromatographic procedures were used to separate 12 lipids. Radioactivity was measured in each lipid, and the amount (ng) of [14C]AA incorporated into each lipid was calculated. Conceptuses and endometrium incorporated more [14C]AA into triacylglycerols than into any other lipid. Day and tissue type affected differentially (i.e., day X tissue interaction) the incorporation of [14C]AA into several lipids; d-14 conceptuses incorporated [14C]AA more actively than did any other day-tissue combination. Results indicate that triacylglycerols may be an important reservoir for conceptus and endometrial AA. The remarkable ability of d 14 conceptuses to incorporate [14C]AA into various lipids may be important for their accelerated elongation and active prostaglandin synthetic system. PMID- 1438878 TI - Receptor-mediated effect of a synthetic thromboxane-analogue on cytosolic calcium in isolated proximal tubules. AB - The aims of this study were to measure cytosolic calcium concentration -[Ca2+]i- under resting conditions in isolated renal proximal tubules and to analyze the effect of U-46619 (stable analogue of thromboxane A2/PGH2 on [Ca2+]i in a mammalian epithelium. Proximal tubules were dissected out from male New Zealand rabbits (2.5 to 3.0 kg). After isolation they were washed twice and resuspended in 2 ml phosphate buffer solution (PBS). Tubules were loaded with Quin 2-AM (25 microM) for 15 min. After washing with PBS to eliminate the excess of extracellular Quin 2, fluorescence was measured at 340 nm excitation and 490 emission, under resting conditions and after stimulation. U 46619 (from 10 nm to 10 mM) increased [Ca2+]i in a concentration-dependent pattern. Exposure to an antagonist of the thromboxane receptor (S-145) blocked the response to U-46619. Removal of external calcium abolished the response to U-46619. Change of PBS for Ringer-choline blunted the response to thromboxane analogue. Our results indicate that U-46619 increases cytosolic calcium through a receptor-mediated mechanism that requires external calcium to operate. Blockade of the response in the absence of external sodium suggests that Na+/Ca2+ exchanger participates in this response. PMID- 1438879 TI - The F2-isoprostane, 8-epi-prostaglandin F2 alpha, a potent agonist of the vascular thromboxane/endoperoxide receptor, is a platelet thromboxane/endoperoxide receptor antagonist. AB - F2-isoprostanes are a recently discovered series of prostaglandin (PG)F2-like compounds that are produced in vivo in humans by nonenzymatic free radical catalyzed peroxidation of arachidonic acid. One of the compounds that can be produced in abundance by this mechanism is 8-epi-PGF2 alpha. 8-epi-PGF2 alpha is a potent vasoconstrictor in the rat, an effect that has been shown to be mediated via interaction with vascular thromboxane (TxA2)/endoperoxide (PGH2) receptors. In an effort to further understand the biological properties of this prostanoid in relation to its ability to interact with TxA2/PGH2 receptors, we examined its effects on human and rat platelets. At concentrations of 10(-6) M and 10(-5) M, 8 epi-PGF2 alpha induced only a shape change in human platelets and at higher concentrations (10(-4) M) induced reversible but not irreversible aggregation. Both the shape change and reversible aggregation were unaffected by indomethacin but were inhibited by the TxA2/PGH2 receptor antagonist SQ29548. Conversely, 8 epi-PGF2 alpha inhibited platelet aggregation induced by the TxA2/PGH2 receptor agonists U46619 (10(-6) M) and IBOP (3.3 x 10(-7) M) with an IC50 of 1.6 x 10(-6) M and 1.8 x 10(-6) M, respectively. 8-epi-PGF2 alpha also inhibited platelet aggregation induced by arachidonic acid. Similarly, in rat platelets, 8-epi-PGF2 alpha alone induced only modest reversible aggregation but completely inhibited U46619-induced aggregation. PMID- 1438880 TI - DuP 753, the selective angiotensin II receptor blocker, is a competitive antagonist to human platelet thromboxane A2/prostaglandin H2 (TP) receptors. AB - DuP 753 is a potent, selective angiotensin II type 1 (AT1) receptor antagonist. The possibility was investigated that DuP 753 may crossreact with thromboxane A2/prostaglandin H2 (TP) receptors. DuP 753 inhibited the specific binding of the TP receptor antagonist [3H]SQ 29,548 (5 nM) in human platelets with kd/slope factor values of 9.6 +/- 1.4 microM/1.1 +/- 0.02. The AT2-selective angiotensin receptor ligand, PD 123,177 was a very weak inhibitor of specific [3H]SQ 29,548 binding in platelets (Kd/slope factor:200 microM/0.86). [3H]SQ 29,548 saturation binding in the absence and presence of DuP 753 resulted in an increase in equilibrium affinity constant (Kd: 9.3, 22, 33 nM, respectively) without a concentration-dependent reduction in binding site maxima (Bmax: 3597, 4597, 3109 fmol/mg protein, respectively). Platelet aggregation induced by the TP receptor agonist U 46,619 was concentration-dependently inhibited by DuP 753 (IC50 = 46 microM). These data indicate for the first time that DuP 753 is a weak but competitive antagonist at human platelet TP receptors. PMID- 1438881 TI - A possible role of prostaglandin E2 in reproduction of the male water frog, Rana esculenta. In vivo and in vitro studies. AB - Plasma prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), androgens and estradiol-17 beta were measured in the male water frog, Rana esculenta, during the annual sexual cycle. In vivo experiments were carried out to study the effects of PGE2 and PGF2 alpha on plasma sex steroids during the following periods: prereproduction (April), reproduction (May), postreproduction (June) and recovery (October). In the same months, in vitro experiments were performed to evaluate the effects of these two prostaglandins (PGs) on testicular release of sex steroids. The PGE2 plasma levels peaked in April. PGE2 treatment in vivo increased androgens in April and October, while PGF2 alpha increased estradiol-17 beta in June and October. In in vitro experiments, PGE2 increased androgens in April, while PGF2 alpha increased estradiol-17 beta in October. These results suggest that PGE2 could induce the breeding activity, probably through androgens synthesis. PGF2 alpha could interrupt the breeding, through estradiol-17 beta secretion. PMID- 1438882 TI - Molecular evolution of cyclooxygenase and lipoxygenase. AB - Four oxygenases of the arachidonic acid cascade (cyclooxygenase, 5-lipoxygenase, 12-lipoxygenase and 15-lipoxygenase) were investigated by the method of computer assisted sequence comparison. From the calculations, some aspects of evolution and function of these enzymes were revealed. (1) The evolutionary origin of cyclooxygenase was different from that of lipoxygenases. (2) Cyclooxygenase was a distantly related member of a peroxidase family. (3) Enzymes with 12-lipoxygenase activity were created independently twice by gene duplication. PMID- 1438883 TI - Analysis of the eicosapentaenoic acid (EPA) metabolite delta 17-6-keto-PGF1 alpha in human plasma by GC/SIM using [18O] delta 17-6-keto-PGF1 alpha. AB - A method of the microdetermination of delta 17-6-keto-PGF1 alpha, a hydrolyzed metabolite of PGI3, is described. An authentic delta 17-6-keto-PGF1 alpha (120 mg) was prepared from eicosapentaenoic acid (EPA) incubated with homogenate of bovine aortic intima. [18O]delta 17-6-Keto-PGF1 alpha was synthesized by repeating base-catalyzed hydrolysis of methyl ester derivatives in [18O]water, to obtain an internal standard in gas chromatography/selected ion monitoring (GC/SIM) of delta 17-6-keto-PGF1 alpha. Good linear response over the range of 10 pg-10ng was demonstrated. Chromatographic conditions using a MP-65HT column presented nearly baseline separation of delta 17-6-keto-PGF1 alpha and 6-keto PGF1 alpha. We were able to detect delta 17-6-keto-PGF1 alpha in the range from 6 to 26 pg/ml of the human plasma. The present method can be applied to the determination of delta 17-6-keto-PGF1 alpha in the human urine and plasma. PMID- 1438884 TI - Pharmacological modulation of prostacyclin and thromboxane production of rat and cat venous tissue slices. AB - To reveal a potential modulating effect of vasoactive pharmacological agents on the prostanoid production of the venous wall, prostacyclin and thromboxane release from venous tissue slices was studied. Aortic and caval vein samples from 20 rats as well as from 21 cats were studied. Prostacyclin and thromboxane productions were determined by radioimmunoassay as 6-keto-PGF1 alpha and TxB2 released into the incubation medium. Venous tissue produced significantly less prostacyclin per unit weight than arterial tissue in rats (30.7 +/- 4.6 vs. 52.1 +/- 8.2 pg/mg/min), while in cats an opposite situation was found (16.6 +/- 3.2 vs. 7.06 +/- 1.9 pg/mg/min). Thromboxane production of venous tissue was consequently higher than corresponding values for aortic tissue (3.72 +/- 0.46 vs. 1.54 +/- 0.14 in rats and 3.4 +/- 0.6 vs. 1.33 +/- 0.19 in cats, all values in pg/mg/min). Norepinephrine and dopamine significantly increased both the prostacyclin and the thromboxane release from venous tissue, while isoproterenol had no effect. Vasopressin significantly increased thromboxane release and decreased the ratio of prostacyclin vs. thromboxane production (from 10.4 +/- 1.6 to 7.5 +/- 1.6, in acetylsalicylic acid pretreated cats). Angiotensin and thrombin had no significant effects. Bradykinin (0.5 microgram/ml) significantly augmented prostacyclin release from venous tissue (14.4 +/- 2.6 from 10.9 +/- 2.4 pg/mg/min) and decreased thromboxane release (0.65 +/- 0.18 from 1.35 +/- 0.22 pg/mg/min). Methionine-enkephalin (5 micrograms/ml) significantly reduced the thromboxane release from venous tissue slices. The presented material demonstrates that several vasoactive agents modulate the vasoactive prostanoid release of the venous wall. In some cases, the prostacyclin and the thromboxane productions are influenced separately, which in turn will have its impact on smooth muscle activity and thrombocyte aggregation. PMID- 1438886 TI - Serum concentrations of secretory IgA in pregnancies delivering at term or preterm. AB - Secretory component (SC) is a phospholipase A2 inhibitor possibly associated with pregnancy maintenance and in serum is bound either to IgA (sIgA) or IgM (sIgM). To determine if serum secretory component levels a) increase during pregnancy, b) fall as term approaches, c) are low in women who will deliver prematurely, serum sIgA was measured at "booking in" and related to weeks of gestation and length of gestation at subsequent noninduced delivery. Levels of sIgA increased during pregnancy; sIgA increased from a non-pregnant value of 1.6 nM +/- 0.2 (mean +/- SEM) to 2.8 nM +/- 0.3 at the end of the second trimester, then fell significantly between 31-34 weeks. Delivery before 37 weeks was associated with significantly reduced serum sIgA levels, particularly in women who delivered before 32 weeks and in whom sIgA concentrations were similar to those of nonpregnant women. PMID- 1438885 TI - Stimulated release of arachidonate and prostaglandins is vectorial in MDCK epithelial cells. AB - The receptor mediated activation of phospholipase A2 by appropriate ligands results in the synthesis and release of eicosanoids, a class of potent bioregulatory molecules. Madin-Darby canine kidney cells (MDCK) are polarized epithelial cells, with structurally and functionally distinct plasma membrane domains separated by tight junctions. Using MDCK cells grown in dual sided chambers, we show in this report, that a) the receptor mediated release of prostaglandins and arachidonate into the extracellular medium is predominantly unidirectional, b) the direction of release is agonist specific, and c) the magnitude of the response due to a given agonist is cell-domain specific. These characteristics, if operative in vivo, would contribute towards the optimal function of trans-cellular metabolism of eicosanoids already demonstrated. PMID- 1438887 TI - [Archaeology of childhood. Psychoanalytic conditions for realizing childhood daydreams exemplified by Heinrich Schliemann]. AB - The biographical value of Heinrich Schliemann's memories of his childhood has always been disrupted. Following W.G. Niederland, the author characterises the famous archaeologist's powers of recall as instances of hypermnesia and not as retrospective constructs. In addition he shows that ontogenetically the conditions governing the realisation of infant ambitions are bound up with original experiences of happiness, traumatic losses without destruction of psychic substance, attempts at reparation and the preservation of the balance between the reality principle and the pleasure principle. A further factor shown to be involved is the dialectic tension between eros and thanatos. With reference to Freud's concept of the archaic heritage, the phylogenetic conditions and their links with ontogenesis are then identified with a view to elucidating why Schliemann, whose childhood ambition it was to excavate Troy, was later able to realise this boyhood dream. PMID- 1438888 TI - [Communicating literary aspects by non-literary means: references to the unconscious in William Wordsworth]. PMID- 1438889 TI - Enterprise bargaining. PMID- 1438890 TI - Theatre for health. PMID- 1438891 TI - Draft Australian code of ethics for nurses. PMID- 1438892 TI - Defining the role and function of enrolled nurses. PMID- 1438893 TI - Women's experience of crimes of personal violence: a gender analysis of the 1991 Queensland crime victims' survey. PMID- 1438894 TI - Enrolled nurse wage increases. PMID- 1438895 TI - Aged care--'the poor relation' ... the campaign continues. PMID- 1438896 TI - [Disparity of the bone marrow involvement in a 5-year-old boy with primary non Hodgkin's malignant lymphoma of the bone]. PMID- 1438897 TI - [Late complications in patients cured of neoplasms in childhood]. AB - Various late complications of the chemotherapy or radiotherapy have been discussed with special reference to rare life-threatening side-effects. The long term strategy of patient's care and preliminary principles of prevention of above complications have also been presented. It has been emphasized that life threatening complications occurring in a small percentage of patients are not indications for limited or ineffective therapy giving no chance of saving of numerous children. PMID- 1438898 TI - [Subendocardial blood flow index in relation to selected parameters of left ventricular function in patients with aortic valve stenosis]. AB - The aim of our studies was to estimate the relation between the reduction of the subendocardial blood flow, expressed by DPTI/TTI ratio and the grade of aortic stenosis determined by the maximal systolic aortic gradient. Additionally the influence of subendocardial blood flow reduction of left ventricular function and ECG alterations was assessed. The analyzed data were obtained during the cardiac catheterizations in a group of 30 patients (average age 32 years). The mean value of DPTI/TTI ratio was decreased (0.49 +/- 0.2) and associated with the elevated mean value of AGmax (72.2 +/- 38.1 mmHg). Negative correlation between DPTI/TTI and AGmax (r = -0.73; p less than 0.003), DPTI/TTI and LVEDP (r = -0.53; p less than 0.005) occurred. Depression of ST-T segment in EEG and episodes of anginal pain accompanied the reduction of subendocardial blood flow. We concluded that reduction in subendocardial blood flow in patients with SA-may lead subendocardial ischaemia of the left ventricular wall with subsequent of its function. PMID- 1438899 TI - [Status of pulmonary circulation and the presence of regurgitant wave from the left ventricle in primary dilated cardiomyopathy]. AB - The purpose of the study was to analyse relationships between the presence and magnitude of a regurgitant wave from the left ventricle to the left atrium and the state of the pulmonary circulation in patients with primary dilated cardiomyopathy. The study population consisted of 97 patients divided into three subgroups I--41 patients without the regurgitant wave, II--31 patients with the first-degree regurgitant wave, III--25 patients with the second-degree regurgitant wave. Diagnosis was based upon non invasive studies, cardiac catheterization and left ventriculography. Average values of the left ventricular systolic and end-diastolic pressures were similar in all subgroups, whereas the cardiac index was the lowest in the subgroup of patients with a large regurgitant wave to the left atrium. There were no differences in mean values of the pulmonary artery pressures, total pulmonary resistance and pulmonary vascular resistance between the patients without the regurgitant wave (subgroup II). In contrast the patients with a large regurgitant wave (subgroup III) showed statistically significantly higher pulmonary artery pressures, higher total pulmonary resistance and pulmonary vascular resistance. In 64% of the patients of this subgroup the left atrium was said to be large. The results of the present study indicate that even not a large regurgitant wave (second-degree) from the left ventricle to the left atrium leads to secondary pulmonary hypertension in patients with primary dilated cardiomyopathy. PMID- 1438900 TI - [Results of the treatment of acute renal failure in 3 selected dialysis units in southern Poland 1981-1990]. AB - The results of the treatment of patients with acute renal failure (ARF) in dialysis units of Krakow, Nowy Sacz and Tarnow were estimated on the basis of prepared questionnaire. The increased number of patients treated because of ARF was demonstrated in the successive years of the study. The mortality rate in the tested group of patients remained about 27%. It depended on the cause of ARF and equalled to 26.7% in medical, 36.7% in surgical, 8% in obstetrical and 6.7 in urological patients, respectively. PMID- 1438901 TI - [Comparison of the value of echocardiographic examination in relation to hemodynamic studies in atrial septal defect of the ostium secundum type]. AB - The aim of the study was in comparative analysis of the results obtained using the cardiac catheterization and the echocardiographic parameters in patients with atrial septal defect of the ostium secundum type. The studies have been performed in the group of 31 patients aged 16 to 58 years (mean = 31.9) in whom the right heart catheterization of the two-dimensional or Doppler's echocardiography has been performed. The following parameters have been analysed: pulmonary flow (Qp), systemic flow (Qs), shunt size (S), the Qp/Qs ratio, the systolic gradient via tricuspidal valve (TPG). The highest correlation in the invasive and the not invasive examination has been shown for TPG (r = 0.93). Other parameters showed no statistically significant differences. PMID- 1438902 TI - [Effect of recombinant human erythropoietin on the bone marrow picture in patients with chronic renal failure treated by hemodialysis]. AB - The influence of recombinant human erythropoietin (rHu-EPO) on anaemia and bone marrow cells was investigated in 7 patients with terminal renal failure on maintenance haemodialysis. The examination was performed immediately prior to rHu EPO treatment (mean hematocrit 20.3%) and after increase of hematocrit to 33%. An increased number of cells from the erythroblastic series and rejuvenation of this population were observed during the treatment. There was no significant influence of the treatment on the myeloblastic cells series. An increase in megakaryocyte activity was observed in 2 studied patients. PMID- 1438903 TI - [Evaluation of worldwide diagnosis and treatment of cancer of the uterine cervix]. PMID- 1438904 TI - [Macrophages: functional heterogeneity of the mononuclear phagocytes]. PMID- 1438905 TI - [Efficiency of the autonomic nervous system in patients with acute leukemia]. AB - Autonomic nervous system function was examined by simple tests in 10 patients with acute myeloblastic leukemia and 10 patients with acute lymphoblastic leukemia. The results in both groups were related to the stage of the disease, clinical and hematological status and mode of chemotherapy. It was found that the functional capacity of the autonomic nervous system was significantly lower in patients with leukemias than in healthy subjects (control group). Functional abnormalities were most prominent in patients in poor clinical condition with marked anemia and during the acute phase of the disease. PMID- 1438906 TI - [Selenium and malondialdehyde levels in the blood serum of men with normo- and hypercholesterolemia]. AB - Lipid peroxidation is a free radical-mediated process. Malonaldehyde (MDA) is one of the products of reduction in this process. Selenium (Se) is a physiological free radical scavenger. In this paper the research on serum selenium (Se), serum MDA (MDAp) and MDA in low density lipoprotein (MDA1) in 52 men (age 38-52 years) will be presented. Plasma total cholesterol (T-chol), free cholesterol (F-chol), esterified cholesterol (E-chol) and triglyceride (Tg) concentrations were estimated also. It was found a significant negative correlation between MDA1 and T-chol (r = -0.4140, p = 0.0023), E-chol (r = -0.3947, p = 0.0038), F-chol (r = 0.4104, p = 0025). The patients were divided according to T-chol level (group I: T-chol greater than 5.2 mmol/l, group II: T-chol less than 5.2 mmol/l). Statistically significant negative correlation were found between: Se and MDAp in both groups (I: r = -0.7734, p = 0.0002, II: r = -0.6695, p = 0.0012), Se and MDA1 only in II group (r = -0.4693, p = 00368). There was no apparent relation between MDAp and T-chol, E-chol, F-chol and Tg. PMID- 1438907 TI - [Complications of liver biopsy in ultrasonic evaluation]. AB - Ultrasound of the right upper quadrant was performed in 261 patients just before and 2-4 h after liver biopsy (Menghini needle 1.4 mm). Serious complications were not seen. 9 patients had ultrasound-detected small hepatic hematomas (1 x 1 cm - 4 x 3 cm) 2-4 h after liver puncture, clinically however irrelevant. Follow-up ultrasound at 24 h and 48 h showed complete resolution of hematomas that had been detected previously (5 patients and 4 patients resp.). The results of our study indicate that intrahepatic hematomas are uncommon after liver biopsy; lesions disappear spontaneously within 24-48 h and that is why ultrasound detection of all post-biopsy intrahepatic hematomas should be performed at 2-4 h. If major complications are not seen a 4 h length of post-biopsy bed rest seems us as sufficiently for all the patients. PMID- 1438908 TI - [Effect of diabetes mellitus type 1 on electric resistance of the skin and galvanic skin response]. AB - Basal electrical resistance of the skin and the galvanic skin response were determined in 102 patients with type I (insulin-dependent) controlled diabetes mellitus. The control group consisted of 121 healthy subjects of the same age and sex distribution. The results obtained imply that diabetes mellitus causes an increase of electrical resistance of the skin, a prolongation of the latency time and or even lacking of the galvanic skin response. PMID- 1438910 TI - [Extracorporeal shockwave lithotripsy (ESWL)--principles of the procedure, indications, results and complications]. PMID- 1438909 TI - [Response of the cardiovascular system in elderly patients to intravenous infusion of isoproterenol and adrenaline]. AB - The effect of gradually increasing doses of catecholamines on the heart rate, arterial pressure and the left heart ventricle systolic time intervals has been studied in the group of 30 aged subjects (70 to 95 years old) and the control group aged 23 to 30 years. The initial resting QS2I, LVETI, PEPI, heart rate and diastolic pressure were similar in both groups studied whereas the chronotropic and inotropic response as well as the vasodilatation were weaker in the aged. The disturbed mechanisms of adaptation in the aged could be caused by limited response of the circulatory system to adrenalin secreted during the stress states. PMID- 1438913 TI - [Percutaneous removal of kidney calculi in children]. PMID- 1438911 TI - [Percutaneous nephrolithotripsy--indications for the procedure and its technique]. PMID- 1438912 TI - [Percutaneous removal of kidney calculi]. PMID- 1438914 TI - [Endoscopic treatment of urinary calculi coexistent with developmental anomalies of the urinary system]. PMID- 1438915 TI - [Chlamydia trachomatis infection of the urogenital system in our clinical experience]. AB - The increased number of the genitourinary system infection caused by Chlamydia trachomatis (Ch. Tr.), increased number of patients with dysuria or sterile leukocyturia gave stimulus to studies of 615 patients from Department of Nephrology and District Outpatient Nephrological Care Unit with regard to infections with that microbes. Material for investigations derived from urethra. Diagnostic examinations were performed using the Mc Coy cell culture and the immunofluorescence method. The infection was noted in 176 patients (119 women and 57 men) that is in 28.6% of cases studied. The mean age of patients was 42.7 +/- 12 years. Clinical symptoms such as dysuria or frequency were typical for that kind of infection. The most frequent abnormality was leukocyturia or leukocyturia accompanied by erythrocyturia noted in 66% of patients. Isolated erythrocyturia was observed in 24.4% of cases. It has been stated that anamnesis or routine laboratory examinations were not able to the identification of infection. In face of poorly characteristics of clinical picture of infection the infection with Ch.Tr. could be the cause of unsuccessful therapy in patients with signs of genitourinary tract infections. PMID- 1438916 TI - [Estimation of the dialysis time based on a simplified algorithm for urea kinetics]. AB - A simplified method of calculating the dialysis time based upon urea kinetic modeling equation: Ct = C0 e exp - (Kt/V) is presented together with a table of urea clearance values for most commonly used dialyzers. The method is handy and helpful to prescribe dialysis time either in chronic uraemics or in patients with acute renal failure on hemodialysis. Estimation of a patient's urea distribution volume equal to the total body water and blood flow through the dialyzer are the key points in the described calculations. PMID- 1438917 TI - [Sensitivity of multiresistant bacterial strains to imipenem (Tienam)]. AB - The susceptibility to imipenem of 213 clinical strains of Gram-negative rods resistant to six cephalosporins (cephradine, cefamandole, cefuroxime, cefotaxime, cefoperazone and ceftriaxone) has been studied. It was found that 93.9% of the strains were sensitive and 6.1% were resistant to imipenem. In the examined group 64 (30%) out of 213 strains were simultaneously resistant to four aminoglycosides (gentamycin, tobramycin, netilmicin and amikacin); among them 5 (7.8%) strains were resistant to imipenem. Sensitivity to imipenem 157 out of 213 examined strains as compared to that of ceftazidime was as follows: 29.3% of the strains were sensitive and 3.8% resistant to both of the antibiotics, whilst 64.3% were imipenem-sensitive and ceftazidime-resistant. In vitro imipenem proved to be very active antibiotic against over 90% of multiresistant Gram-negative rods. PMID- 1438918 TI - [Gastric secretion in chronic erosive gastritis]. AB - In 50 patients with erosive gastritis the basic and the post-pentagastrin secretion of hydrochloric acid or glycoproteids has been studied. The results obtained have been compared with that in healthy subjects. No significant differences between the both groups investigated have been noted. It has been stated that chronic erosive gastritis could be associated with normal, elevated or lowered hydrochloric acid secretion. The results are of value with regard to the choice of treatment but remain without significance for diagnostics. PMID- 1438919 TI - [Effect of carbon dioxide (CO2) pressure on minute ventilation, parameters of gas exchange and blood gases during hemodialysis using fluid containing acetate and bicarbonate buffers]. AB - In 20 patients with chronic renal failure on a hemodialysis with acetate containing dialysing fluid gasometric, ventilation and breathing patterns disturbances were determined. The loss of CO2 in the dialysate is attributed the major cause of hypoxemia due to alveolar hypoventilation. Hemodialysis with bicarbonate-containing dialysate can be performed in the absence of any change in ventilation and PaO2 despite a systemic alkalosis. Hyperventilation during HD with high concentration of bicarbonate indicate that changes in CO2 tension in the pulmonary circulation can lead to a change in minute ventilation due to the presence of slowly adapting pulmonary chemoreceptors. In patients with low respiratory response, respiratory muscle weakness intensified additionally by hypercapnia may explain this phenomenon. PMID- 1438920 TI - [Pathogenesis of acute pancreatitis--review of the literature]. PMID- 1438922 TI - [Menstruation as a cause of hemoperitoneum during peritoneal dialysis. Case report]. PMID- 1438921 TI - [Biological and clinical aspects of chronic granulomatous disease]. PMID- 1438923 TI - [Glomerulonephritis in Schoenlein-Henoch purpura. Report of 9 cases]. PMID- 1438924 TI - Electrolyte disturbances caused by intravenous contrast media. AB - The changes in serum electrolytes (sodium, potassium, ionized calcium, and total calcium) produced by high-dose (3 ml/kg) intravenous contrast media were investigated in Japanese white rabbits. The test solutions included sodium/meglumine diatrizoate (370 mgI/ml), sodium/meglumine ioxaglate (320 mgI/ml), iohexol (350 mgI/ml), iopamidol (370 mgI/ml), 20% mannitol, and isotonic saline. The alterations in serum ionized calcium were relatively small and transient, and correlated with changes in the hematocrit. Diatrizoate caused a significant decrease in ionized calcium in comparison with other contrast media and mannitol. The ratio of ionized calcium to total calcium showed no significant decrease in any group. The changes in potassium did not correlate with those in hematocrit. Diatrizoate caused a smaller decrease in potassium than low osmolality contrast media, which may suggest that diatrizoate caused a shift in potassium from extravascular space to intravascular space. In conclusion, intravenous infusion of high doses of low-osmolality contrast media did not cause clinically significant alterations in serum electrolytes. PMID- 1438925 TI - MRI of anterior mediastinal tumors. AB - To compare the abilities of MRI (magnetic resonance imaging) and CT to provide information about anterior mediastinal tumors, we retrospectively evaluated the MR (n = 28) and CT images (n = 25) of patients with anterior mediastinal tumors. T1-weighted and T2-weighted images were obtained with spin echo sequences using cardiac gating. Six of 12 thymomas and seven of nine teratomas showed characteristic findings by MRI, while four of the 10 thymomas and five of the eight teratomas were correctly diagnosed by CT. The other tumors did not show a characteristic MR appearance. All nine malignant tumors were correctly diagnosed as malignant lesions on MR images, while one false positive case and one false negative case were recorded on CT images. We conclude that MRI and CT provide nearly the same information for the evaluation of anterior mediastinal tumors. However, in some cases, only MRI can provide information about malignancy or a specific diagnosis. PMID- 1438926 TI - Quantitation of cerebral blood volume by 99mTc-DTPA-HSA SPECT. AB - The characteristics of technetium-99m diethylenetriaminepentaacetic acid human serum albumin (99mTc-DTPA-HSA) as an agent for quantitation of cerebral blood volume (CBV) were examined. The radioactivity after decay correction as a percentage of the activity at 10 minutes was 84.3 +/- 1.3% at 120 minutes after the injection of 99mTc-DTPA-HSA. Radioactivity was found exclusively in plasma, with little in blood cells. The blood retention of 99mTc-DTPA-HSA is sufficient, and its use in the quantitation of CBV omits the need for centrifugation of the blood sample. CBV quantified using the tracer and a SPECT system with a single head rotating gamma camera was 4.09 +/- 0.60 ml/100 g brain, similar to values reported previously. Two serial SPECT scans provided similar images, and the CBV values determined by the two scans were closely correlated (p < 0.001). The high reproducibility suggests that the method may be used to monitor the cerebrovascular response to drugs. It was concluded that 99mTc-DTPA-HSA has useful properties for quantitative CBV measurement and that quantitation of CBV by 99mTc-DTPA-HSA SPECT is feasible using a system with a single-head rotating gamma camera. PMID- 1438929 TI - High dose rate gynecological applications--radiobiological considerations based on the alpha-beta model. AB - We compare the relative efficacy of high dose rate (HDR) and low dose rate (LDR) irradiation in gynecological implants, using formulations based on the linear quadratic (alpha-beta) model. We consider both acute reaction and late effect as endpoints in evaluating equivalence for HDR and LDR treatments, at Point A (as defined in the text) and at other locations. We define a therapeutic factor gamma as an index for relative efficacy, with gamma > 1 indicating a gain in substituting HDR for LDR. It is found that gamma < 1 for most clinical situations, although a modest decrease (of about 15%) in dose to critical organs for HDR would raise gamma above unity. PMID- 1438928 TI - Multilocular cystic hemangioma: CT and MR appearance. AB - An atypical case of multilocular cystic hemangioma is presented. A 4.5 cm multilocular cystic mass was incidentally found in a 66-year-old healthy woman on ultrasound screening. CT, MR imaging, and angiography were performed: however, the features that are characteristic of cavernous hemangioma were not obtained. The final diagnosis could not be made until surgery. PMID- 1438930 TI - In vivo dosimetry during pelvic treatment. AB - High precision in vivo entrance and exit dose measurements have been performed with p-type diodes on patients during 8 MV X-ray irradiation of the pelvis, to investigate the accuracy of dose calculations in this region. Based on phantom measurements the accuracy of the p-type diode measuring system itself, i.e. the agreement with ionisation chamber dose measurements, was shown to be better than 0.7% while the reproducibility in the dose determination was 1.1%, 1.5% and 1.6% (1 S.D.) at the entrance point, isocentre and exit point, respectively, for the wedged lateral fields. Patient movement and the uncertainty in the diode position increased these values to 1.7%, 1.5% and 3.1% (1 S.D.) for dose determinations on patients. From the entrance and exit in vivo dose values the dose actually delivered to the isocentre was determined. For the anterior-posterior beams a good correspondence for most patients was observed at the entrance and exit point and at the isocentre between the in vivo and calculated dose values. For the wedged lateral beams a systematic deviation of about 3% was observed. In addition to the in vivo dose measurements phantom dose measurements have been performed to quantify the accuracy of the dose calculation algorithms including the computation of the number of monitor units. These measurements also served to quantify the effects of the actual patient on the dose delivery. The measurements showed that accurate calculation of the dose requires a separation of the head and phantom scatter contribution of the output of the treatment machine. The dependence of the wedge factor on field size, depth and source-skin-distance has also to be considered for accurate dose calculations. The effect of the patient on the dose calculation is mainly related to the actual electron densities of fat and bone structures compared to water: neglecting these densities in the dose computation could yield deviations up to 8.5% for the exit point in wedged beams. Based on these results, improvements in the dose calculation algorithms and monitor unit calculation including the use of the actual electron densities will be implemented in the treatment planning procedure. PMID- 1438927 TI - Radiation therapy for stage I and II laryngeal cancer using 10 MV X-rays or cobalt-60 gamma-rays. AB - From 1970 to 1985, 117 patients with stage I and stage II carcinoma of the larynx (98 with glottic, 15 with supraglottic, and 4 with subglottic cancer) received radiation therapy. The patients were treated with (1) a 60Co machine equipped with 45-degree wedge filters, at a total dose of 6,000-7,000 cGy, 300 cGy per fraction, 3 days a week in the period from 1970-1974; (2) 10 MeV linear accelerator X-rays from 1975-1980, and (3) 10 MeV linear accelerator X-rays and/or the 60Co machine in the period from 1981-1985, at a total dose of 6,000 7,000 cGy, 5 days a week by parallel opposing portals without wedge filters. The 5-year local control rates by radiotherapy alone were 66%, 78%, and 83%, respectively, in the three periods, and the 5-year survival rates were 77%, 97%, and 96% following salvage surgery for recurrent disease. In the 1970-1974 period, four patients developed severe laryngeal edema, and two patients had total laryngectomy without local residual tumor. In the 1975-1985 period, 16 patients had local recurrence in five years, and in five of them the tumor exhibited verrucous-like histopathological findings. In the 1975-1980 period, local recurrence was considered to result from underdosing of lesions with 10 MV X-ray beams and split-course irradiation. In the last five years of the period, the 5 year local control rate for stage I and II carcinoma of the glottis, excluding verrucous-like carcinoma, reached 90% with 10 MV X-rays combined with 60Co gamma rays. PMID- 1438931 TI - Glass yttrium-90 microspheres for patients with colorectal liver metastases. AB - Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. Median survival was 11 months (range 5-25 + months). PMID- 1438932 TI - Tandem-vaginal cylinder applicator for radiation therapy of uterine adenocarcinoma. AB - Preoperative radiotherapy for stage II adenocarcinoma of the endometrium was studied in 74 patients using the University of Kentucky tandem-vaginal cylinder applicator. The intrauterine tandem and vaginal cylinder were inserted and loaded at the same time or sequentially. Forty to 45 Gy of fractionated whole pelvis photon radiotherapy was combined with the single intracavitary insertion which gave 20 Gy to a parauterine isodose at 2 cm and to the vaginal surface. Treatment with this system gave a 5 year survival rate of 88% with a 4% complication rate for stage II corpus adenocarcinomas. PMID- 1438933 TI - No clinical evidence for the influence of overall treatment time on TCD50 of head and neck tumours. PMID- 1438934 TI - Overall treatment time and tumor control dose for head and neck tumors: the dog leg revisited. PMID- 1438935 TI - My experience in low dose-rate radiotherapy. PMID- 1438936 TI - Quality control at the patient level: action or retrospective introspection. PMID- 1438937 TI - Reirradiation by interstitial brachytherapy alone of cancers of the oropharynx in previously irradiated areas. PMID- 1438938 TI - Nodal treatment for patients with early stage breast cancer: guilty or innocent? PMID- 1438939 TI - Selective avoidance of lymphatic radiotherapy in the conservative management of early breast cancer. AB - In view of the morbidity and potential mortality associated with routine post operative lymph node radiotherapy in women with early stage breast cancer, an attempt has been made to select patients in whom radiotherapy can be withheld. Three hundred and forty-seven consecutive patients treated wide local excision plus or minus axillary surgery have been evaluated. Only 20% were subsequently given radiotherapy to regional nodes. Relapse in the axilla, the supraclavicular fossa or at both these sites have occurred in 16 patients so far, 12 of whom were successfully treated. Systemic relapse was seen in eight of these patients occurring with one exception before or within 3 months of node relapse. Only four have persisting symptoms as a result of nodal relapse. So far, a policy involving selective lymphatic radiotherapy in women treated for early breast cancer appears justified. PMID- 1438941 TI - Orchidectomy followed by radiotherapy in 176 stage I and II testicular seminoma patients: benefits of a 10-year follow-up study. AB - Results are presented for 176 patients with stage I and II primary testicular seminoma treated at the Dr. Daniel den Hoed Cancer Center (DDHCC) between 1975 and 1985. The median follow-up time was 7 years and 4 months. One-hundred and seventy-four (99%) of these patients were treated primarily with radiotherapy after extensive staging. According to the Royal Marsden Staging Classification, 132 patients (75%) were stage I, 8 (5%) were stage IIA, 21 (12%) were stage IIB, 9 (5%) were stage IIC and for 6 stage II patients a further subdivision was not possible. At 5 years the actuarial relapse-free survival and the actuarial survival were 95 and 99%, respectively, for stage I, and 77 and 91% for stage II. Prophylactic irradiation of the mediastinum has not been performed for stage II patients. Five stage II patients relapsed in the mediastinum. Four out of these five relapses were cured with chemotherapy, and in one case, in combination with radiotherapy, at the time of relapse. These results indicated that prophylactic irradiation of the mediastinum appeared to be unnecessary for stage II patients. Tumour markers were not useful in the discovery of metastases. Five years after treatment no relapses were seen. Therefore, it is proposed that a maximum follow up of 5 years is sufficient to measure disease-free survival. PMID- 1438940 TI - Prostate cancer treated by radiotherapy: a multivariate study. AB - According to respective proportions of evolutive status groups, results of multivariate studies are difficult to interpret. Among the 1099 cases of local form of prostate cancer, treated by radiotherapy from 1975 to 1982 in 16 French Anticancer Institutes, we can observe two homogeneous status groups of patients: disease-free survivors (285 cases) and patients who died of prostate cancer (278 cases). These correspond to 51% of the whole population. Among other things, they are comparable in size, for age at the beginning of radiotherapy and for delay between histologic diagnostic and radiotherapy. We chose to analyse them using multivariate analysis. To take survival into account, we used a Cox model and Kaplan-Meier curves; the group deceased of prostate cancer was further analyzed by a tree-structured regression method. The Cox model and the Kaplan-Meier curves confirmed two main explicative factors: Stage (p < 0.0001) and tumor grade (p < 0.001). Poorer evolution occurs in extracapsular forms and grade I has better survival than others. The tree-structured regression method indicates two other pejorative factors: hormonotherapy prior to radiotherapy and the presence of cardiovascular pathology. Though the pelvic dose does not appear to be a main explicative factor, it seems to improve survival and delay between radiotherapy and recurrence or metastasis in some categories of cases. Other factors such as tumor dose, age and delay between diagnosis and radiotherapy were not found to be significant. These results cannot be extended to the whole population for which they do not constitute a predictive study. We consider them as "baseline data".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438943 TI - Gonadotrophin-induced oestrus and ovulation in the polyovulatory marsupial Sminthopsis crassicaudata. AB - Sminthopsis crassicaudata is a small (approximately 16 g) polyovulatory dasyurid marsupial which has the potential to become an important model species. This study examined the use of exogenous hormone treatment to manipulate the breeding of S. crassicaudata and as a means to obtain timed developmental stages for further study. Two thirds (21/32) of the females treated with 1.0 or 5.0 I.U. of pregnant mare serum gonadotrophin (PMSG) had ovulated when the contents of their reproductive tracts were examined 5 or 6 days later. Only one of eight females treated with 0.2 I.U. PMSG had ovulated in the same period. Although a similar proportion of animals treated with 1.0 I.U. and 5.0 I.U. ovulated, the ovulation rate was significantly lower when the higher dose was administered (mean of 10.5 ovulations per female v. 3.8 ovulations per female). In addition, the ovaries of 6/8 of the animals treated with 5.0 I.U. PMSG had luteinized follicles with degenerating oocytes, evidence of over-stimulation. Follicular luteinization also occurred in 4/8 animals treated with 1 I.U. PMSG. Oocyte maturation and ovulation occurred following PMSG stimulation without injection of synthetic gonadotrophin releasing hormone (GnRH). Treatment with a 10-micrograms dose of GnRH following PMSG seemed to have no effect on the outcome. Of the females that had ovulated by Day 6, three quarters had mated and some had fertilized eggs and two-cell embryos in the oviducts and uteri. In a further series of experiments the subsequent development of embryos conceived after PMSG treatment was assessed. Two thirds of treated females mated within 7 days of treatment and 60% of these matings yielded embryos when examined 11 days after PMSG. However, full-term development was only achieved in one animal. Gonadotrophin treatment of S. crassicaudata thus may have application as a means to obtain mature or maturing oocytes, cleavage stage embryos and blastocysts, but at this stage it appears not to offer promise as a method to achieve full-term development. PMID- 1438942 TI - Some effects of feeding Tribulus terrestris, Ipomoea lonchophylla and the seed of Abelmoschus ficulneus on fetal development and the outcome of pregnancy in sheep. AB - Pregnant ewes and their fetuses were chronically catheterized using aseptic procedures under general anaesthesia, and the ewes were then fed either lucerne chaff alone, or lucerne mixed with dried plant material obtained from one of three forb species, Tribulus terrestris (caltrop), Abelmoschus ficulneus (native rosella) or Ipomoea lonchophylla (cowvine), from 103-112 days gestation until term. Ingestion of the forb material was not associated with changes in maternal blood gases, plasma glucose concentrations, or the length of gestation. However, ingestion of rosella seed was associated with a significantly greater fall of fetal arterial pO2 with advancing gestation, and ingestion of either rosella or cowvine was associated with significantly lower fetal mean arterial pressure at 127-131 days, compared with the Tribulus and lucerne groups. Also, the incidence of fetal breathing movements was significantly lower, and did not show a normal day-night variation, in each of the forb-fed groups compared with the lucerne-fed group. The results indicate that these forb plants may contain substances that affect the functional development of the fetal brain. Although ingestion of these plants did not appear to affect the outcome of pregnancy in this study, the possibility that these forbs have a greater impact in sheep populations with poor nutrition and in more extreme environmental conditions is discussed. PMID- 1438944 TI - Comparison of a swim-up technique with the Hamilton Thorn Motility Analyser for measurement of sperm velocity and motility. AB - A colorimeter-based swim-up (SU) technique was developed and compared with a Hamilton Thorn Motility Analyser (HTM) for the evaluation of ram semen. SU parameters (sperm velocity in microns s-1, proportion of rapidly moving spermatozoa, and motility index) were significantly correlated (r from 0.47 to 0.98, P from < 0.05 to < 0.001) with most HTM parameters in semen containing known proportions of motile and immotile spermatozoa and in semen that was cold shocked, aged, diluted-stored and frozen-thawed. There were, however, no significant correlations between sperm velocity and HTM parameters in the fresh semen studied, possibly because of the small number of observations (n = 21) and narrow range of semen quality (83 +/- 2% subjectively scored motility) available. It is concluded that the swim-up technique is a simple, cheap, objective and reliable means of measuring sperm velocity and motility in ram semen. PMID- 1438945 TI - Effects of the progesterone antagonist RU486 on myometrial activity in vivo in early pregnant and pseudopregnant rats. AB - Myometrial activity in vivo was quantified by video-laparoscopy in early pregnant rats given doses of RU486 which caused embryo abortion and blocked the action of progesterone on the vagina. All treatments diminished the frequency of circular contractions and abolished the curling movements of the uterus which are characteristic of pregnant, pseudopregnant and progestin-treated rats. The effects of RU486 on circular contractions were similar in pseudopregnant rats, i.e. they were not a consequence of embryo abortion. These results support the thesis that increased myometrial circular contractions in early pregnancy and pseudopregnancy are induced by increasing levels of progesterone. Effects of RU486 on longitudinal contractions were more complex: the highest dose inhibited longitudinal contractions on Day 5 of pregnancy and pseudopregnancy, but increased their frequency on Day 6. The acute inhibition of longitudinal contractions by RU486 was unexpected and the mechanism remains to be elucidated. The later increase in the frequency of longitudinal contractions appears to be due to antagonism of progesterone by RU486. The frequency of caudal longitudinal contractions on Day 6 in mated rats given RU486 was similar to that in unmated oestrous rats, but the frequency of cranial longitudinal contractions was significantly higher. These results support the hypothesis that stimuli received during copulation may have long-term effects on myometrial activity, by increasing pacemaker activity at the cervix. PMID- 1438946 TI - Addition of superoxide dismutase and catalase does not necessarily overcome developmental retardation of one-cell mouse embryos during in-vitro culture. AB - There is evidence that developmental blocks observed in mouse embryos during culture in vitro may be the result of free radical-induced cellular dysfunction. We have further investigated this possibility by examining the effects of 5% O2 and the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), on mouse 1-cell embryo development. The results demonstrate that development of CF-1 strain embryos is enhanced by incubating in 5% CO2, 5% O2, 90% N2 (5/5/90) compared with 5% CO2 in air (5/air) (P < 0.01) and by culturing in the presence of other embryos. Superoxide dismutase significantly improved embryonic development (35 +/- 5% v. 17 +/- 4% morulae/blastocysts, P < 0.001) at a concentration of 100 units mL-1 when embryos were gassed under 5/5/90. At a concentration of 1000 units mL-1, SOD was detrimental to development (P < 0.001). Injection of SOD and/or CAT into embryos had not effect on development. Development has also been examined in four strains of mice (CF-1, Quackenbush (random-bred strains), Balb-C (inbred) and the F1 hybrid of CBA x C57B1) in the presence or absence of 100 units SOD mL-1 and 1000 units CAT mL-1. Embryonic development was markedly different among the four strains examined, with F1 hybrid > Balb-C (P < 0.001), Balb-C > CF-1 (P < 0.05) and Quackenbush embryos performing very poorly compared with the embryos of the other three strains (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438947 TI - Comparison of the SpermMar test with currently accepted procedures for detecting human sperm antibodies. AB - To eliminate the possibility of immunological infertility in spontaneously infertile and re-anastomosed men, a screening test that can be applied directly to semen is desirable. The SpermMar test is one such possibility. In this study, indirect tests for sperm antibodies using the commercial SpermMar test have been applied to a panel of sera whose reactions in the tube slide agglutination test (TSAT), gelatin agglutination test (GAT) and sperm immobilization test (SIT) for sperm antibodies are well characterized. The results from the SpermMar tests are compared directly with those obtained from Immunobead tests carried out at the same time. Results from screening tests performed on 30 sera confirmed complete correspondence between the GAT, SpermMar and Immunobead tests. When sera were titrated, the Immunobead test proved slightly more sensitive than the GAT and the SpermMar test was slightly more sensitive than the Immunobead test. The SpermMar test proved easier to use and to assess than the Immunobead test and it is recommended for consideration as a screening procedure for sperm antibodies despite the fact that at this stage only IgG antibodies can be detected. PMID- 1438948 TI - Characterization and autoradiographic localization of the epidermal growth factor receptor in the jejunum of neonatal and weaned pigs. AB - Receptors for epidermal growth factor (EGF) were characterized on the intestinal membranes of newborn, sucking and weaned pigs. 125I-labelled EGF (125I-EGF) binding to membrane homogenates was time-dependent, saturable, linearly correlated to membrane protein and reversible. Analysis of saturation curve data revealed a single class of 125I-EGF binding sites in both newborn and weaned pigs. Receptor levels tended to be higher in weaned than in newborn pigs; the converse was true for the receptor affinity. In contrast, virtually no binding sites were found on the intestinal membranes of sucking pigs. Autoradiography in vitro of jejunal sections of newborn and weaned pigs demonstrated 125I-EGF receptors on both microvillar and basolateral surfaces of enterocytes, suggesting that luminal EGF could influence developmental processes in the intestine either directly or indirectly following transcytosis of the ligand. PMID- 1438949 TI - Differential mRNA expression of the phosphoprotein p19/SCG10 gene family in mouse preimplantation embryos, uterus, and placenta. AB - The p19/SCG10 gene family encodes two structurally related cellular proteins that are implicated in signal transduction during differentiation of mammalian cells. Previous evidence suggests that both genes are expressed in a stage-specific manner but that expression of p19 is widespread, whereas that of SCG10 is restricted to developing neurons. To determine at which developmental stage these two genes are first expressed, we have probed for mRNA transcripts in preimplantation embryos and the utero-placental unit of the mouse. As determined by polymerase chain reaction (PCR) to amplify reverse-transcribed RNA, expression of both genes was detected in preimplantation embryos, although the temporal pattern was distinct. p19 mRNA appeared transiently in 2-cell embryos, was undetectable in morulae and early blastocysts and reappeared in expanded blastocysts. In contrast, embryonic expression of SCG10 mRNA commenced in morulae and was maintained through to the blastocyst stage. Interestingly, only SCG10 expression could be detected in blastocysts derived from cultures of 2-cell embryos. During the post-implantation period, SCG10 transcripts were only detected in the uterus and placenta by reverse transcriptase-PCR, whereas p19 mRNA could be detected by Northern blotting and showed stage-specific expression in both tissues. The data confirm that, at later developmental stages, expression of p19 is widespread while that of SCG10 is more restricted. The expression of both genes in preimplantation embryos suggests distinct but possibly overlapping roles for p19 and SCG10 in early mammalian development. PMID- 1438950 TI - Duration of the cycle of the seminiferous epithelium and quantitative histology of the testis of the South American white-belly opossum (Didelphis albiventris), Marsupialia. AB - The duration of the cycle of the seminiferous epithelium of the South American white-belly opossum, as obtained by autoradiography after intratesticular injection of tritiated thymidine, was estimated to be 17.3 +/- 0.1 days (mean +/- s.d.). Quantitative histological analysis was performed on testes from animals caught both in mating and non-mating periods of the annual reproductive cycle. Significant differences were found in the volumetric proportion of Leydig cells, but the spermatogenic yield remained constant throughout the year. The numerical ratio between type A spermatogonia and zygotene primary spermatocytes (1:12.0), as well as daily sperm production (4.8 x 10(6) sperm cells per g of testis parenchyma per day), were found to be lower than those reported in most eutherian mammals. PMID- 1438951 TI - Monoclonal anti-idiotypic antibody to progesterone with internal image properties. AB - An auto-anti-idiotypic approach was used to generate mouse monoclonal anti idiotypic antibody E9F11F6 (Ab2) to progesterone. A conjugate of 4-pregnane 3,20 dione and bovine serum albumin was used as the immunogen. E9F11F6 bound to a rabbit anti-progesterone antibody in a linear concentration-dependent manner. It inhibited the binding of [3H]progesterone to a monoclonal anti-progesterone antibody, E9D5 (Ab1); this inhibition was concentration dependent. Results from chase experiments showed that this inhibitory activity of Ab2 was not due to steric hindrance but was a result of direct binding to the ligand combining site. Indirect immunofluorescence studies also showed that Ab2 and progesterone bound to similar binding sites on Ab1. Overall, the results suggest that E9F11F6 contains an internal image of at least part of the progesterone molecule, and that it can be classified as an Ab2 beta antibody. This anti-idiotypic antibody may be of value in further studies of endocrine and reproductive physiology. PMID- 1438953 TI - Effect of ovariectomy on blastocyst expansion and survival in ferrets (Mustela putorius furo). AB - The initial objective was to investigate whether progesterone alone can support full blastocyst expansion in ferrets ovariectomized on Day 5 post coitum (p.c.). By Day 11 p.c. blastocysts from control animals had expanded to approximately 2000 microns in diameter, whereas by Days 11 or 14 p.c. blastocysts from ovariectomized animals given progesterone had diameters of < 1000 microns. Thus, ovarian factors in addition to progesterone are apparently required for normal blastocyst expansion in this species. Subsequent experiments indicated that an initial stage of expansion (from approximately 200 microns to approximately 400 microns) occurred regardless of whether ovariectomy was performed on Day 2 or 3 p.c. A second stage of expansion resulted in blastocysts of approximately 700 microns in diameter and it occurred in ovariectomized animals if progesterone was given or if ovariectomy was delayed until Day 5 p.c. A third phase of expansion resulted in blastocysts of approximately 2000 microns in diameter and occurred only if ovariectomy was delayed until Day 8 p.c. Although blastocyst expansion appeared normal in these animals, implantation did not occur in the absence of progesterone replacement. In addition, blastocysts retained in the oviduct by ligation of the uterotubal junction failed to expand beyond approximately 400 microns in diameter. These results suggest that progesterone acts upon the uterus to promote blastocyst expansion up to a diameter of approximately 1000 microns and that additional ovarian factors are required for further blastocyst expansion. PMID- 1438952 TI - Differential pituitary response to GnRH in pregnant Booroola-Assaf and Assaf ewes. AB - Pituitary response to exogenous gonadotrophin-releasing hormone (GnRH) was examined at a late stage of pregnancy in 10 Booroola-Assaf ewes heterozygous at the FecB locus (FecBFec+) and in 11 Assaf ewes that were non-carriers (Fec+Fec+). Basal plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations were similar in the two genotypes. Administration of 100 micrograms of GnRH resulted in a significant increase (P < 0.05) in plasma LH and FSH concentrations in most of the ewes treated. Maximal responses were observed 105-135 min after GnRH treatment. Pituitary responses to GnRH were significantly lower (P < 0.05) in Booroola-Assaf than in Assaf ewes. The decreased pituitary responsiveness observed in FecB gene carriers compared with Fec+Fec+ ewes might be due to differences in the concentrations of ovarian or uterine hormones modulating the release of gonadotrophin. The results suggest that FecB-specific differences can be observed at the pituitary level. PMID- 1438954 TI - Oviductal fluid protein patterns in the rhesus monkey (Macaca mulatta) during the menstrual cycle. AB - Oviducts were obtained from monkeys on Days 8, 14, 19 and 25 of the menstrual cycle and changes in the pattern of luminal fluid proteins were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Densitometric analysis after periodic acid Schiff's reagent (PAS) and coomassie blue staining of the gels revealed 85 and 95 kDa proteins only up to Day 14 whereas a 130 kDa glycoprotein persisted up to Day 19 and reached a nadir at mid menstrual cycle (Day 14). The absence of the 130 kDa glycoprotein in the serum and its presence in cytosolic preparations up to Day 19 suggest that it is of oviductal origin. The 130 kDa glycoprotein is of particular interest since it was present in the oviductal fluid during mid cycle, a period when the oviduct participates in gamete transport, fertilization and embryo development. The conclusion drawn from this study is that the protein profile of monkey oviductal fluid changes during the menstrual cycle. PMID- 1438955 TI - Early endometrial microvascular response during implantation in the rat. AB - The endometrial microvasculature becomes intimately involved in the events of early implantation. This paper reviews aspects of this microvascular involvement during implantation in the rat. There is a major increase in vascular permeability surrounding the implanting embryo, leading to significant local changes in microvascular architecture. This is followed by a shutdown of the capillaries closest to the embryo as the primary decidual zone develops. At this time, endometrial capillaries adjacent to the primary decidual zone become dilated, with over twice the average diameter of intersite capillaries. Endometrial neutrophils are reduced around the implanting blastocyst, mitigating against a role for these inflammatory mediators in vascular aspects of the implantation process. Angiogenesis does not appear to increase at the implantation site, although there is an increase in production of endometrial endothelial cell migratory signal a few hours prior to the commencement of implantation. PMID- 1438956 TI - Morphometric and freeze fracture studies of human endometrium during the peri implantation period. AB - This paper reviews recent morphological work on peri-implantation endometrium collected from the Monash University In vitro Fertilization (IVF) Programme. Comparisons of endometrial tissue collected from women who had undergone different superovulation regimens demonstrated that significant structural differences could be detected by morphometry and ultrasound, but not by routine histopathology. Morphometric studies on endometrium from agonadal women receiving hormone replacement therapy demonstrated major differences between women with identical endocrine profiles. A biopsy inadvertently taken from one of these patients at the time of implantation was not of the appearance classically believed to be associated with receptivity for implantation. Studies have shown that the tight junction structure of endometrial epithelium is regulated during the menstrual cycle, suggesting that the integrity of the epithelial barrier may be important in the preparation of the endometrium for implantation. PMID- 1438957 TI - Glycoconjugates as positive and negative modulators of embryo implantation. AB - A variety of studies indicate that complex glycoproteins participate in or modulate adhesive interactions occurring during embryo implantation. In particular, proteoglycans and proteins that bind proteoglycans are involved at multiple stages of this process. Identification of these binding proteins and the molecular controls over glycoconjugate expression are required to develop a comprehensive understanding of the implantation process. PMID- 1438958 TI - Studies in vitro of effects of steroid hormones and the blastocyst on endometrial function in the sheep. AB - Normal endometrial function is a result of regulation by the combination of ovarian steroids and local agents arising from within the embryo-maternal unit. We have used in vitro techniques to examine the role of steroid hormones and ovine trophoblast interferon on endometrial function in the ewe. Immunolocalization of oestrogen receptors in endometrial tissue demonstrated marked changes throughout the cycle and in early pregnancy with maximal concentrations during the follicular and very early luteal phases. Protein secretion from highly purified cultured ovine stromal and epithelial endometrial cells, and the direction of secretion from polarized epithelial cells, has been examined by incorporation of [35S]methionine and by one- and two-dimensional gel electrophoresis. Protein synthesis is greater in stromal than in epithelial cells and more protein is secreted apically than basally from epithelial cells. A number of common and some different proteins are secreted by the two cell types. One secreted protein is matrix metalloproteinase-3 (stromelysin) which degrades components of basement membranes. Ovine trophoblast interferon attenuates the production of prostaglandins from ovine endometrial cells but its action is not by an effect on localization or concentration of the enzyme prostaglandin synthase or on expression of the gene for prostaglandin synthase. Such studies in vitro contribute to our understanding of how the endometrium is prepared for implantation. PMID- 1438959 TI - Embryo-derived platelet activating factor. AB - Platelet-activating factor (PAF) is secreted by the preimplantation embryo of a number of species. The role of this secretion is yet to be fully elucidated. Evidence to date indicates that it has an important function as an autocrine stimulant of embryonic metabolism, growth and viability. Production of PAF by embryos appears to be severely compromised in vitro. This may be a major cause of reduced embryo viability following embryo culture and it may also help to explain the controversy in the literature regarding the production of PAF by embryos. PAF also alters several aspects of maternal physiology during early pregnancy including endometrial prostaglandin secretion. The significance of these changes remains to be defined. PMID- 1438960 TI - Roles of prostaglandins (PG) F2 alpha, E1, E2, adenosine, oestradiol-17 beta, histone-H2A and progesterone of conceptus, uterine or ovarian origin during early and mid pregnancy in the ewe. AB - Pregnancy does not prevent the local transfer or accumulation of prostaglandin F2 alpha (PGF2 alpha) by the corpus luteum (CL), the number of receptors for PGF2 alpha or the binding of PGF2 alpha to the CL. However, the conceptus does depress the response of the CL to PGF2 alpha during early pregnancy. PGE1 and PGE2 appear to be blood-borne antiluteolysins that are delivered locally to prevent the actions of PGF2 alpha during early pregnancy, since they prevent luteolysis only when given by chronic intrauterine infusion adjacent to the ovary with the CL. The concentrations of PGE1 and PGE2 in the endometrium and PGE2 in uterine venous plasma increase during early pregnancy. A Day 10 embryo transferred to a Day 6 progestagen-primed recipient ewe advances the time at which PGE2 is secreted. The uterine venous PGE/PGF2 alpha ratio is 12:1 at midgestation, and exogenous PGF2 alpha increases the placental secretion of oestradiol-17 beta. This is followed by increases in PGE secretion when endogenous PGF2 alpha increases. Both oestradiol-17 beta and PGE may protect placental secretion of progesterone from PGF2 alpha, since PGF2 alpha causes the CL to regress but does not affect placental progesterone or pregnancy in the presence or absence of the ovary. PMID- 1438961 TI - Nutrition-progesterone interactions during early pregnancy in sheep. AB - A series of studies was undertaken to determine the relationship between level of feed intake during early pregnancy, concentrations of peripheral progesterone and embryo survival in sheep. Ewes fed twice maintenance (2M) rations after joining had a pregnancy rate of 48%. Ewes fed 2M rations and given exogenous progesterone between 8 and 14 days after mating had a pregnancy rate of 76%. Ewes fed rations calculated to maintain live weight (maintenance, M) or fed restricted rations during this same time had pregnancy rates ranging from 60 to 68%, with no beneficial effect of progesterone supplement. Concentrations of peripheral plasma progesterone on Day 12 after mating were inversely related to the level of feed intake; this relationship reflected an increase in the metabolic clearance rate of progesterone with increased feed intake (1/2M, M and 2M) without concomitant changes in the entry rate of the hormone. Injection of epostane, an inhibitor of the enzyme 3 beta-hydroxysteroid dehydrogenase, caused 'windows' of progesterone reduction for 48-h periods over Days 9-13 after mating. The sheep embryo was sensitive to low peripheral plasma progesterone concentrations only on Days 11 and 12 after mating. Blood flow rates in the portal vein of ewes fed either 1/2M, M or 2M rations for 7 days were directly related to the level of feed intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438962 TI - Endocrine events associated with endometrial function and conceptus development in cattle. AB - Regulation and timing of luteolysis during the bovine oestrous cycle is controlled by the initiation and length of progesterone stimulation. Results have demonstrated that early administration of progesterone shortens the interoestrous interval in the ewe and cow, and removal of progesterone stimulation through a progesterone receptor antagonist delays luteolysis in sheep. Current data suggest that down-regulation of progesterone receptors in the uterine epithelium may initiate events involved in the synthesis and release of prostaglandin F2 alpha (PGF2 alpha) for luteolysis. Progesterone is also involved in the stimulation of the uterine secretions that regulate conceptus growth and the release of the bovine trophoblast protein-1 (bTP-1) necessary for inhibiting endometrial PGF2 alpha release. Conceptus secretion of bTP-1, a Type I trophoblast interferon, increases the concentration of the cellular enzyme 2',5'-oligoadenylate synthetase within the endometrium. The biological role of 2',5'-oligoadenylate synthetase in the establishment of pregnancy is discussed. PMID- 1438963 TI - Uterine secretion of prostaglandin F2 alpha in the ewe: regulation at the cellular level by ovarian hormones and the conceptus. AB - Changes in the ability of the uterus to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin may play a critical role in determining when endogenous secretion of PGF2 alpha begins. The cellular mechanisms that regulate uterine secretion of PGF2 alpha in response to oxytocin have not been completely defined. Several intracellular components that may contribute to this regulation have been studied, including phospholipase C (PLC), prostaglandin H endoperoxide synthase (PGS) and receptors for oxytocin. All of these components change during the oestrous cycle and are associated with the development of uterine secretory responsiveness to oxytocin. Progesterone appears to play the principal role in regulating oxytocin receptors, PLC and PGS. The conceptus appears to suppress the increase in receptors for oxytocin and PLC activity that typically occurs around the time of luteal regression. PMID- 1438964 TI - Regulation of bovine endometrial prostaglandin secretion and the role of bovine trophoblast protein-1 complex. PMID- 1438965 TI - Roles of ovine trophoblast protein-1 and oestradiol/prolactin in the establishment of pregnancy in sheep and pigs. PMID- 1438966 TI - Cellular regulation of corpus luteum function during maternal recognition of pregnancy. PMID- 1438967 TI - Genes for the trophoblast interferons and their distribution among mammals. AB - The trophoblast interferons (IFN), ovine and bovine trophoblast protein-1 (oTP-1 and bTP-1 respectively), possess many properties in common with other Type I IFN, including antiviral and antiproliferative activities. However, they differ from other IFN subtypes in terms of their specific pattern of expression and poor responsiveness to viral stimulation. We describe here data that suggest that the trophoblast IFN genes are also distinct from other Type I IFN genes with respect to species distribution, promoter organization and transcriptional regulation. These results have important implications in terms of trophoblast IFN gene evolution and add credence to the concept that the trophoblast IFN genes are a distinct IFN gene subtype well suited for their role in early pregnancy. PMID- 1438968 TI - Neutral endopeptidase modulates endothelin-1-induced airway smooth muscle contraction in guinea-pig trachea. AB - This study was designed to evaluate the role of neutral endopeptidase (NEP) in modulating the airway smooth muscle contraction induced by endothelin-1 in isolated segments of guinea-pig trachea. Endothelin-1 (10(-9)-10(-6) M) produced a concentration-dependent contraction that reached a maximum by 30 min. The NEP inhibitor leucine-thiorphan (10(-5) M) significantly increased the contractile response to endothelin-1. The addition of leucine-thiorphan to tracheal segments precontracted by 10(-9) and 10(-8) M endothelin-1 increased isometric tension by 181 +/- 65% (mean +/- 1 S.E.M.; P less than 0.05) and by 138 +/- 49% (P less than 0.05), respectively. In contrast, the kininase II inhibitor captopril and the peptidase inhibitors leupeptin and bestatin had no effect. Preincubation of endothelin-1 with 1 microgram recombinant human NEP decreased the contractile activity of endothelin-1 by 72 +/- 9%, whereas no effect was observed using heat inactivated NEP. We conclude that NEP modulates endothelin-induced contraction of airway smooth muscle in the guinea-pig trachea. PMID- 1438969 TI - Different relative abundance of neurotensin and neuromedin N in bovine ocular tissues. AB - Neurotensin (NT) and neuromedin N (NN) are regulatory peptides encoded by the same gene and located in tandem within a common precursor. Using specific radioimmunoassays for both peptides, their relative abundance in extracts of bovine ocular tissues has been examined. Within the retina, the molar concentration of NN was significantly higher (P less than 0.001) than that of NT. In contrast, within both choroid/sclera and iris/ciliary bodies, the molar concentration of NT was significantly higher (P less than 0.001) than that of NN. These data demonstrate that the theoretical molar ratio of 1:1, which would result from complete processing of both peptides from the common precursor, does not occur in any of the ocular tissues examined. Reverse phase HPLC of extracts of each ocular tissue confirmed the differential abundance of NT and NN. These data would suggest that the common NT/NN precursor is differentially-processed within bovine ocular tissues, a finding which may be of physiological significance. PMID- 1438970 TI - The effect of TGF alpha on intestinal solute transport. AB - The effect of transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) on 3-O-methylglucose transport was examined in vitro under short circuited conditions in stripped rabbit jejunum. Mucosal EGF, 60 ng/ml, stimulated a significant increase in net 3-O-methylglucose transport (Jnet 0.67 +/- 0.15 vs. 0.90 +/- 0.15 microEq/cm2/h; P less than 0.03; n = 6) due to an increased mucosal to serosal flux (Jms 1.2 +/- 0.2 vs. 1.5 +/- 0.2 microEq/cm2/h; P less than 0.03). In contrast, TGF alpha, when applied to both mucosal and serosal surfaces at concentrations of either 60 (n = 6) or 150 (n = 9) ng/ml had no effect on either mucosal to serosal (Jms) or net transport (Jnet) of 3-O methylglucose. TGF alpha did induce a significant increase in the serosal to mucosal flux (Jsm 60 ng/ml 0.44 +/- 0.02 vs. 0.51 +/- 0.03, 150 ng/ml 0.55 +/- 0.03 vs. 0.64 +/- 0.05 microEq/cm2/h; P less than 0.05). When brush border surface area was examined after exposure to either 60 ng/ml TGF alpha or saline vehicle for 2 h in in vivo isolated jejunal loops no significant difference was found (control 53 +/- 1.9; n = 35 vs. TGF alpha 52 +/- 1.9 microns 2; n = 29). Bioactivity of transforming growth factor alpha was assessed by an gastric acid secretion bioassay and found to be intact. These data provide further evidence for separate and distinct functional roles for these peptides in some biological systems. PMID- 1438971 TI - Influence of VIP on the number of enterochromaffin and mucosal mast cells in the colon of the rat. AB - The possibility that VIP (Vasoactive intestinal peptide) could influence the enterochromaffin (EC) cell secretion of serotonin (5HT) and the action of VIP on the mast cell population of lamina propria were investigated in Wistar rat colon infused with a short chain fatty acid solution (sodium acetate), during a 1 h period. Under the action of an intravenous injection of synthetic porcine VIP, 14 micrograms/kg/h), the number of EC cells diminished significantly in the cecum and left colon, when compared to non-injected animals, both infused with a sodium acetate solution. At the same time, the number of mucosal mast cells in the crypts and lamina propria decreased significantly in the cecum. The postulate we put forward is that these VIP-induced changes are exerted through the stimulation of 5HT released from EC cells not only under normal physiological conditions but probably also under pathological conditions. PMID- 1438972 TI - Immunodetection of secretogranin II in animal and human tissues by new monoclonal antibodies. AB - Secretogranin II (chromogranin C) is an acidic tyrosine-sulfated secretory protein, known to be a marker of neuroendocrine secretory products and of specific neuroendocrine tumours. In order to obtain anti-secretogranin II monoclonal antibodies for cell biology studies and, in particular, for clinical applications, we immunized mice with a secretogranin II-enriched fraction prepared from homogenates of bovine anterior pituitaries. Hybridoma supernatants obtained from the splenocytes of a hyperimmune mouse, screened with an enzyme linked immunosorbent assay, were analyzed by both immunocytochemistry and two dimensional immunoblotting. By using this experimental approach, we were able to identify two monoclonal antibodies (8G1 and 5A7) which recognize bovine secretogranin II. Both immunocytochemistry and immunoblotting revealed that one of them, the 5A7 antibody, cross-reacts with the human antigen. The distribution patterns of the immunoreactivity, obtained by immunocytochemistry with the 5A7 antibody in animal and human tissues, partially overlap those, obtained by using a polyclonal antiserum elicited against bovine secretogranin II, previously described. Moreover, the 5A7, but not the polyclonal antibody, reacts with some duodeno-jejunal cells. In conclusion, both the 5A7 and 8G1 antibodies can be useful for cell biology studies. The 5A7 antibody can be used for the detection of secretogranin II in human tissues and should be of help in clinical and pathological practices. PMID- 1438973 TI - Neuropeptide Y 16-36 inhibits mucociliary activity but does not affect blood flow in the rabbit maxillary sinus in vivo. AB - Recent investigations have shown neuropeptide Y (NPY) to be present in the rabbit maxillary sinus, and NPY is known to be released upon sympathetic nerve stimulation. To study, in vivo, the effect on mucociliary activity and blood flow, NPY 1-36 and some of its analogues were injected intra-arterially. The effects of the Y1/Y2 agonist NPY 1-36 was compared with the ones of the Y2 agonist NPY 16-36, the Y1-agonist [Leu31,Pro34]NPY and the Y1/Y2 agonist peptide YY. Mucociliary response was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity immediately prior to challenge. The effect on blood flow was measured with laser Doppler flowmetry and expressed as a percentage of the mean blood flow during the 60 s preceding challenge. NPY 1-36 and NPY 16-36 both reduced mucociliary activity dose-dependently at equimolar dosages (0.024-1.2 nmol/kg). The greatest effect was seen after the highest dosage tested. NPY 1-36 reduced mucociliary activity by 14.6 +/- 1.8%, and NPY 16 36 by 13.2 +/- 1.4%. At the highest dosage tested the Y1 receptor agonist [Leu31,Pro34]NPY did not significantly reduce mucociliary activity, whereas PYY reduced mucociliary activity by 15.0 +/- 1.8%. Injections of NPY 16-36 had no effect on blood flow whereas NPY 1-36, [Leu31,Pro34]NPY and PYY all reduced blood flow dose-dependently. Maximal decrease was seen at the highest dosage tested and was 47.1 +/- 5.4%, 70.4 +/- 7.4% and 58.2 +/- 8.4%, respectively. These findings suggest the mucociliary effects to be mediated via Y2 receptors whereas blood flow is regulated via Y1 receptors. PMID- 1438974 TI - Effect of chymotrypsin on human cholecystokinin release: use of clostripain in the validation of a new radioimmunoassay. AB - We have developed and validated a new radioimmunoassay for cholecystokinin. In order to establish that the antiserum binds large and small forms of CCK to an equal extent, we used the microbial enzyme clostripain, which cleaves large forms of CCK yielding CCK 8. Cleavage by clostripain of synthetic and purified forms of CCK, and CCK extracted at from human jejunum and CCK in human plasma was found not to affect immunoactivity, indicating that the antiserum reacts similarly with all forms of CCK. There is controversy over whether intraduodenal trypsin inhibits release of CCK in man. We used our radioimmunoassay to investigate whether chymotrypsin, rather than trypsin, could be the major mediator of negative feedback control of CCK release. Six normal subjects received an intraduodenal infusion of L-phenylalanine and L-tryptophan on two occasions, with the addition of either 1 g/l bovine chymotrypsin or 1 g/l albumin. Plasma CCK concentrations rose in response to the amino acid infusion, but were not affected by the addition of chymotrypsin, indicating that this enzyme is not a mediator of CCK feedback regulation in man. PMID- 1438975 TI - Cardiovascular and respiratory actions of pituitary adenylate cyclase-activating polypeptides. AB - Effects of pituitary adenylate cyclase-activating polypeptide (PACAP38) and PACAP27 on the cardiovascular and respiratory systems were examined and compared to those of vasoactive intestinal polypeptide (VIP) in anesthetized beagle dogs. Intravenous PACAP27 and PACAP38 produced a decrease in mean arterial blood pressure (MBP), and an increase in both femoral arterial blood flow (ABF) and in frequency of respiration (FR) with a dose-dependent relationship between 10 and 300 pmol/kg. PACAP27 produced a dose-dependent increase in heart rate (HR) between 10 and 300 pmol/kg while PACAP38 induced tachycardia which was not dose dependent. Administration of 300 pmol/kg PACAP38 and PACAP27 produced extreme hypertension after transient hypotension. PACAP38 produced severe bradycardia after transient tachycardia. The cardiovascular actions of PACAP38 were persistent compared to those of PACAP27. Intravenous injection of 10-300 pmol/kg VIP brought about hypotension, tachycardia and an increase in ABF and FR with a dose-dependent relationship. VIP, at 2000 pmol/kg, did not produce the biphasic response obtained by a large dose of PACAP38. The present studies demonstrate that PACAP partially possesses VIP-like cardiovascular and respiratory actions and that the C-terminal 11 amino acid residues of PACAP38 are presumably responsible for a prolongation of its actions. PMID- 1438976 TI - Functional control of chromogranin A and B concentrations in the body of the rat stomach. AB - The chromogranins are soluble, acidic, proteins which are frequently co-stored in neuroendocrine cells with biogenic amines. In the gastric mucosa chromogranin A is localized to enterochromaffin-like cells which are the main source of histamine, and which are known to be regulated by circulating gastrin. We have used radioimmunoassays selective for the extreme C-terminal regions of chromogranin A and B to examine changes in gastric extracts following modulation of the gastric luminal contents. There were decreased concentrations of the two chromogranins in tissue extracts of rats after food withdrawal (which lowered plasma gastrin concentrations); inhibition of acid secretion with the H+/K(+) ATPase inhibitor, omeprazole (which increased plasma gastrin concentrations) raised chromogranin A and B concentrations both in fasted rats, and in rats fed ad libitum. There was no evidence for altered patterns of posttranslational cleavage of chromogranin A or B with these treatments. The data indicate that chromogranin A and B concentrations in gastric ECL cells are regulated in parallel with histamine production, and are consistent with the idea that the chromogranins play a role in the formation and stabilization of the secretory granule involved in amine storage. PMID- 1438977 TI - Vasoactive intestinal polypeptide (VIP) inhibits rat alveolar macrophage phagocytosis and chemotaxis in vitro. AB - Vasoactive intestinal polypeptide (VIP) has been shown to inhibit lymphocyte function and is believed to modulate the immune response. We explored the possible immunomodulatory effects of VIP on alveolar macrophage (AM) function by examining its influence on AM phagocytosis and chemotaxis. Rat AMs were collected by bronchoalveolar lavage and incubated for 90 min with polystyrene beads in the presence or absence of VIP in concentrations from 10(-11) M to 10(-5) M. VIP significantly (P less than 0.0001) inhibited AM phagocytosis of polystyrene beads at concentrations of 10(-11) to 10(-6) M, with a maximal inhibition of 35% at 10( 6) M (but no inhibition at 10(-5) M). AMs were also incubated for 90 min in a chemotaxis chamber with endotoxin-activated rat serum (EARS) as a chemoattractant, with or without VIP in concentrations from 10(-9) to 10(-6) M. VIP significantly (P less than 0.0001) inhibited AM chemotaxis by at least 30% at concentrations of 10(-9) to 10(-6) M, with a maximal inhibition of 46% at 10(-7) M. These results indicate that VIP, in concentrations from 10(-11) to 10(-6) M, inhibits rat AM function as assessed by phagocytosis of polystyrene beads and chemotaxis to EARS. The inhibition of alveolar macrophage function is another mechanism by which VIP may modulate the immune response in the lung. PMID- 1438978 TI - Unlike VIP, the VIP-related peptides PACAP, helodermin and helospectin suppress electrically evoked contractions of rat vas deferens. AB - We have compared the effects of vasoactive intestinal peptide (VIP) and of the VIP-related peptides pituitary adenylate cyclase activating peptide (PACAP) 1-27 and 1-38, helodermin, helospectin I and helospectin II, on the electrically evoked twitches in the isolated vas deferens of the rat. While VIP was virtually without effect, PACAP 1-38 suppressed the electrically evoked twitches effectively and in a concentration-dependent manner (pIC50 value 7.5). The naturally occurring N-terminal fragment PACAP 1-27 was less effective than PACAP 1-38 (Imax values 37.2% suppression compared to 76.5%) and less potent. The C terminal fragment PACAP 16-38 was virtually inactive. Also helodermin and helospectin I+II suppressed the electrically evoked twitches effectively and in a concentration-dependent manner (pIC50 values 6.9; 7.2; 6.8, respectively). The three peptides produced similar maximum reduction of the twitches (74-80%). The findings suggest that PACAP, helodermin and helospectin suppress the electrically evoked contractions in the rat vas deferens via receptors distinct from VIP receptors. PMID- 1438979 TI - Difference between the antisecretory mechanisms of opioids and the somatostatin analogue octreotide in cholera toxin-induced small intestinal secretion in the rat. AB - The antisecretory effect of morphine and the somatostatin analogue octreotide was studied on cholera toxin-induced secretion in anaesthetized rats. Small intestinal secretion was induced with cholera toxin. Morphine (6 mg/kg b.wt.) and the somatostatin analogue octreotide (3 micrograms/kg b.wt.) reduced the cholera secretion in rats whose intestines had been subjected to sympathetic denervation. This was in contrast to the secretion elicited by helodermin which was unaffected by octreotide and morphine in the presence of nicotinic ganglionic blockade. The alpha-adrenergic receptor blocker phentolamine (1-2 mg/kg b.wt. i.v.) and the inhibitor of sympathetic transmitter release guanethidine (5 mg/kg b.wt. i.v.) abolished the antisecretory effect of morphine on the cholera secretion in contrast to the antisecretory effect of somatostatin which was unaffected by the alpha-blockade. It is proposed that the antisecretory effect of morphine and octreotide on cholera toxin-induced secretion was conducted at a step prior to the activation of the secretory epithelium and that the antisecretory effect of morphine was mediated indirectly by interaction with sympathetic nerve terminals in the intestine. The findings are consistent with a model where octreotide and morphine inhibit the nervous secreto-motor reflex activated by the cholera toxin. PMID- 1438980 TI - Helospectin-like immunoreactivity in the esophagus. AB - Helospectin I and II are two non-amidated, VIP-like peptides, isolated from the salivary gland venom of the lizard Heloderma horridum. The lower esophagus of cat, sheep and man was analyzed for helospectin-like immunoreactivity. Immunocytochemistry revealed helospectin-immunoreactive nerve fibers in the muscle layers, submucosa and mucosa of all species studied. In myenteric ganglia helospectin-immunoreactive nerve fibers and nerve cell bodies could be seen. Double immunostaining for helospectin and vasoactive intestinal peptide (VIP) revealed their coexistence in nerve fibers and cell bodies throughout the lower esophagus of all species tested. Double immunostaining for helospectin and neuropeptide Y revealed their coexistence in nerve fibres surrounding vascular and non-vascular smooth muscle. In the cat and sheep (but not in man) a subpopulation of the helospectin/VIP-containing fibers stored, in addition, substance P. The helospectin-immunoreactive material in the esophagus probably constitutes a novel neuropeptide. The distribution of the VIP/helospectin immunoreactive neurons and fibers indicates their possible involvement in the regulation of motor and secretory activities. PMID- 1438981 TI - Bivariate assay for cleaved atrial natriuretic factor (ANF(101-105/106-126)) in sheep plasma. AB - A bivariate assay has been developed to measure both ANF, and cleaved ANF (ANF(101-105/106-126)) the primary product of endopeptidase-24.11 action on rat ANF(101-126). The assay employed two different antisera directed to the carboxy terminal and ring regions of ANF to enable discrimination and measurement of intact endogenous ANF(99-126) and infused cleaved ANF (rat ANF(101-105/106-126)) in sheep plasma extracts. The assay which was validated by HPLC analysis of plasma extracts, had sufficient accuracy and precision to measure the metabolic clearance rate and half-life of cleaved ANF when infused in normal sheep. PMID- 1438982 TI - Molecular cloning, sequence analysis and translation of proenkephalin mRNA from rat heart. AB - Proenkephalin mRNA is abundant in rat cardiac ventricles but surprisingly low levels of opioid peptides or precursor forms derived from proenkephalin are present in tissue extracts. Proenkephalin mRNA in rat heart was characterized at the molecular level with the use of cDNA sequencing, in vitro translation, and primer extension. Two positive proenkephalin cDNA clones were obtained by screening approx. 20,000 recombinant phages from a heart cDNA library. Sequence analysis of the cDNA clones indicated that the heart transcript was the same form as in rat brain, but differed from the germ cell-specific testis transcript that utilizes a different transcriptional start site. Heart proenkephalin cRNA translated efficiently, resulting in the synthesis of a 35 kDa protein that was immunoprecipitated by an antibody specific to the protein. The transcriptional initiation sites utilized in the heart were the same as in the brain, based on primer extension studies. These data suggest that the proenkephalin transcript found in abundance in rat heart is the same form as found in the brain, and differs from the testis-type transcript. We conclude that the scant level of proenkephalin-derived peptides in the heart is not due to an intrinsic inability of the proenkephalin transcript to translate. PMID- 1438983 TI - Discovery of a distinct binding site for angiotensin II (3-8), a putative angiotensin IV receptor. AB - We report here the discovery of a unique and novel angiotensin binding site and peptide system based upon the C-terminal 3-8 hexapeptide fragment of angiotensin II (NH3(+)-Val-Tyr-Ile-His-Pro-Phe-COO-) (AII(3-8) (AIV)). This fragment binds saturably, reversibly, specifically, and with high affinity to membrane-binding sites in a variety of tissues and from many species. The binding site is pharmacologically distinct from the classic angiotensin receptors (AT1 or AT2) displaying low affinity for the known agonists (AII and AIII) and antagonist (Sar1,Ile8-AII). Although a definitive function has not been assigned to this system in many of the tissues in which it resides, AIV's interaction with endothelial cells may involve a role in endothelial cell-dependent vasodilation. Consequent to this action, AIV is a potent stimulator of renal cortical blood flow. PMID- 1438984 TI - Role of cholecystokinin in mediating GRP-stimulated gastric, biliary and pancreatic functions in man. AB - To explore the mechanisms of gastrin-releasing peptide (GRP)-induced gut functions in man, we investigated the effect on gallbladder contraction, exocrine pancreatic secretion and gastric acid secretion of a recently developed CCK receptor antagonist, loxiglumide, on GRP-stimulated effects in six healthy human subjects. Intravenous infusion of graded doses of synthetic human GRP (1-27 pmol/kg per h) caused significant and dose-dependent increases in pancreatic enzyme and gastric acid secretions and in gallbladder contraction. Intravenous administration of loxiglumide (10 mg/kg per h) abolished GRP-stimulated gallbladder contraction, augmented gastric acid secretion, but did not affect exocrine pancreatic secretion. The results suggest that endogenously released CCK is (1) responsible for GRP-stimulated gallbladder contraction, and (2) involved in regulating gastric acid secretion. The results further suggest that GRP stimulated pancreatic secretion is not mediated by CCK, but has a direct response of GRP on the exocrine pancreas. PMID- 1438985 TI - Measurement of T-kinin in rat plasma using a specific radioimmunoassay. AB - T-kinin (Ile-Ser-Bradykinin) has been isolated only from the plasma of the rat and it is unclear whether the peptide, or its biosynthetic precursor, T kininogen, circulates in the human. An NH2-terminally directed antiserum to T kinin was raised in rabbits using an immunogen prepared by coupling the free -SH group of T-kinin extended from its COOH-terminus by a cysteinyl residue to an NH2 group on human serum albumin. A radioimmunoassay was developed using this antiserum and 125I-labelled [Tyr10]T-kinin as tracer that was sensitive (least detectable concentration 3 fmol/tube) and relatively specific for T-kinin (cross reactivity with bradykinin and kallidin less than 1%). Treatment of rat plasma with an excess of trypsin in the presence of a kininase inhibitor generated T kinin immunoreactivity equivalent to 455 +/- 71 pmol/ml (mean +/- S.E.M.; n = 9) and this immunoreactivity was eluted from a reversed-phase HPLC column as a single peak with the same retention time as synthetic T-kinin. In contrast, treatment of plasma from healthy human subjects (n = 8) and from patients (n = 8) with inflammation due to acute or chronic gastrointestinal disease under the same conditions did not generate any detectable T-kinin immunoreactivity. It is concluded, therefore, that T-kininogen, the biosynthetic precursor of T-kinin in the rat, is either absent from the plasma of human subjects or is present in a concentration less than 30 fmol/ml. Similarly, T-kininogen is probably not an acute phase reactant in humans. PMID- 1438986 TI - Direct effect of bombesin on pancreatic and gastric growth in suckling rats. AB - Bombesin stimulates growth of the stomach and pancreas in adult rats. Part of this effect is thought to be through the release of CCK following bombesin treatment. We studied the effect of long term administration of bombesin on the pancreas and stomach in suckling rats and examined the action of bombesin using specific CCK antagonist (CR-1409) and bombesin antagonists (GRP19-26, D-Phe19, Leu26CH2NHCOCH3 = cpd 17; L-686,095-001C002 = cpd 23). Rat pups (7-days-old) were given bombesin (20 micrograms/kg body wt. twice a day) or vehicle (1% gelatin) for 9 days. Bombesin stimulated pancreatic and gastric growth (tissue weight, total protein and DNA content all increased). Pancreatic trypsinogen concentration and content showed a 2-3-fold increase. CR-1409 at 6 mg/kg body wt., a dose that blocked the trophic action of CCK-33 when given to pups at similar ages, did not affect the bombesin-stimulated growth of the pancreas or the increase in trypsinogen level. At 2.4 mg/kg body wt., cpd 17 partially blocked and cpd 23 completely blocked the trophic effect of bombesin on the pancreas and stomach and the increase in trypsinogen level in the pancreas. RU 486, a type II glucocorticoid receptor antagonist, given at a dose sufficient to block the physiological action of glucocorticoid, had no effect on bombesin stimulated growth of the pancreas. Thus, in vivo, bombesin acts directly on the neonatal pancreas and stomach. PMID- 1438987 TI - Effects of atrial natriuretic factor on norepinephrine release in the rat hypothalamus. AB - The effects of atrial natriuretic factor on the mechanisms involved in norepinephrine release were studied 'in vitro' in slices of Wistar rat hypothalamus. Atrial natriuretic factor (10, 50 and 100 nM) decreased spontaneous [3H]norepinephrine secretion in a concentration dependent way. In addition, the peptide (10 nM) also reduced acetylcholine induced output of norepinephrine. The atrial factor (10 nM) was unable to alter the amine secretion when the incubation medium was deprived of calcium or when a calcium channel blocker such as diltiazem (100 microM) was added. In conclusion, atrial natriuretic factor reduced both spontaneous and acetylcholine evoked [3H]norepinephrine release in the rat hypothalamus. These findings suggest that the atrial natriuretic factor may alter catecholamine secretion by modifying the calcium available for the exocytotic process of catecholamine output. PMID- 1438988 TI - High potency of a new bombesin antagonist (RC-3095) in inhibiting serum gastrin levels; comparison of different routes of administration. AB - This study was performed to evaluate the efficacy and duration of action of a new bombesin antagonist D-Tpi6,Leu13 psi (CH2NH)Leu14-bombesin (6-14) (RC-3095), given by different routes of administration, in suppressing gastrin releasing peptide (GRP(14-27))-stimulated gastrin release in rats. First, we showed that GRP(14-27) itself was highly active when administered by different routes. GRP(14 27), given to rats at a dose of 25 micrograms/100 g b.w. significantly increased serum gastrin levels 3 and 6 min after intravenous and for more than 30 min after subcutaneous administration or pulmonary inhalation. RC-3095 was then injected subcutaneously, intravenously and also delivered by pulmonary inhalation at a dose of 10 micrograms/100 g b.w. in each case to seven male rats 2, 30, 60 or 120 min prior to i.v. administration of 5 micrograms GRP(14-27). RC-3095 administered 2 min prior to GRP(14-27) decreased the gastrin response to GRP(14-27), measured as area under the curve, by 81% in the intravenously injected group and 64% in the pulmonary inhalation group in the first 6 min. When GRP(14-27), was given 30 min after administration of RC-3095, the gastrin response was decreased by 52% in the subcutaneous group, 49% in the pulmonary inhalation group and 11% in the intravenous group during the first 6 min. RC-3095 delivered subcutaneously or by pulmonary inhalation 1 h before GRP(14-27) was also able to significantly inhibit gastrin release. Analysis of the data revealed that the bioavailability of RC 3095 given by the pulmonary inhalation route was about 69% of the s.c. route.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1438989 TI - Localization of calbindin D28K-like immunoreactivity in fish gill: a light microscopic and immunoelectron histochemical study. AB - The presence of calbindin D28K in fish (Heteropneustes fossilis) gill was studied by use of specific antibodies raised against chick duodenal 28 kDa calbindin in immunoperoxidase and electron-microscopic labelling experiments. Immunoreactivity for calbindin D28K, which has been observed in the intestine of a number of avian and mammalian species, is reported for the first time in the gill. It was primarily located in neuroendocrine (NE) cells. Some immunoreactivity was also located in the glycocalyx of the non-endocrine cells, i.e., the pavement cells, which have ultrastructural characteristics quite different from those of endocrine cells. The calbindin-immunopositive NE cells were ascertained in both gill filamental and lamellar epithelium. All the NE cells contained secretory granules as the most distinctive feature of these cells. Ultrastructurally, two types of NE cells were distinguished according to the morphology of their secretory granules. The calbindin immunoreactivity in the NE cells was stimulated when the calcium concentration of the ambient water was reduced. The present findings suggest that NE cells exert some as yet unidentified function related to calcium-mediated processes involving the expression of calbindin. PMID- 1438990 TI - Desmethylimipramine pretreatment prevents 6-hydroxydopamine induced somatostatin receptor reduction in the rat hippocampus. AB - Several studies have shown anatomical and functional interconnections between catecholaminergic and somatostatinergic systems. To assess whether somatostatin (SS) may act presynaptically on catecholamine neurons, SS receptors were measured using radioligand test-tube binding assays on synaptosomes from hippocampus and frontoparietal cortex--areas that are innervated by catecholaminergic neurons with different densities and that have a high number of SS receptors--from control and 6-hydroxydopamine (6-OHDA)-treated rats. Intracerebroventricular (i.c.v.) injection of the catecholamine neurotoxin 6-OHDA (0.78 mg free base/kg of body weight in saline with 0.1% ascorbic acid) lowered hippocampal and frontoparietal cortical noradrenaline (NA) and dopamine (DA) levels at 1 week following the injection. Pretreatment of rats with desmethylimipramine (DMI) (40 mg/kg, intraperitoneal) prevented the drop in NA levels, but was not effective in attenuating DA depletion in the two brain areas studied. Treatment with 6-OHDA lowered the number of 125I-Tyr11-SS receptors in the hippocampus (130 +/- 19 vs. 266 +/- 16 fmol/mg protein, P < 0.001), whereas in the frontoparietal cortex a non significant 20% reduction in receptor number was found. The dissociation constants of 125I-Tyr11-SS binding to synaptosomes from frontoparietal cortex (0.65 +/- 0.06 vs. 0.60 +/- 0.04, P not significant) and hippocampus (0.44 +/- 0.04 vs. 0.63 +/- 0.14, P not significant) were similar in control and treated groups. Pretreatment with DMI reversed up to 80% of the effect of 6-OHDA on hippocampus SS receptors. DMI alone had no observable effect on the number and affinity of SS receptors. The 6-OHDA and the DMI treatment did not affect SLI levels in the brain areas studied. These results suggest that a portion of the hippocampal SS receptors may be localized presynaptically on the noradrenergic and dopaminergic nerve terminals. PMID- 1438991 TI - Adrenalectomy does not change CRF secretion induced by interleukin-1 from rat perifused hypothalami. AB - Interleukin-1 (IL-1) is a potent hypothalamic-pituitary-adrenal (H-P-A) axis activator. The hypothalamus is considered one of the main sites of action of IL-1 on the H-P-A axis, inducing CRF secretion, which is modulated by glucocorticoids. Glucocorticoids, which modulate CRF release by a negative feedback inhibition, have been postulated to exert a permissive action on the IL-1 effect on CRF secretion. Using a continuous perifusion system of rat hypothalami, the results of the present study indicate that at the same concentrations, IL-1 beta exerted a more potent effect than IL-1 alpha stimulating CRF secretion. The increase in hypothalamic CRF release induced by IL-1 was rapidly inhibited by both dexamethasone and corticosterone. However, adrenalectomy 2 or 8 days before did not modify CRF secretion induced by IL-1 from the in vitro perifused hypothalami. These data indicate that IL-1 does not seem to induce CRF secretion by interfering with an impeding action of glucocorticoids, although the cytokine effect is negatively modulated by corticosteroids. PMID- 1438992 TI - Endogenous CCK is not involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs. AB - In this study, we assessed whether endogenous CCK is involved in the regulation of interdigestive gastrointestinal and gallbladder motility in conscious dogs with force transducers chronically implanted in the gastric antrum, duodenum, jejunum and gallbladder. L364718 at a dose of 1.0 mg/kg was used as a specific and potent CCK receptor blocker, and its effect on spontaneous interdigestive motility and plasma motilin release were examined. Additionally, the contractile activity of exogenous synthetic canine motilin (20-100 ng/kg) with or without pretreatment with L364718 at a dose of 1.0 mg/kg was assessed. Whether the blocking effect of L364718 on CCK receptors was sufficient or not was verified by giving CCK-OP at a bolus dose of 10 ng/kg. As a result, cyclic changes in interdigestive motor activity and the plasma motilin concentration were not affected by pretreatment with L364718. L364718 also did not affect motilin induced interdigestive contractile activity in the gastrointestinal tract and gallbladder. On the other hand, the effect of CCK-OP was completely abolished by pretreatment with L364718. It is concluded that endogenous CCK is not involved in the regulation of spontaneous and motilin-induced interdigestive contractions in the canine gastrointestinal tract and gallbladder. PMID- 1438993 TI - Mechanistic data in scientific public health decisions. PMID- 1438994 TI - Codex Committee on Pesticide Residues--a plan for improved participation by governments. AB - The Codex Committee on Pesticide Residues (CCPR), which is responsible for establishing maximum residue limits (MRLs) for pesticides on food, has a vital role in protecting the public health and facilitating international trade. Codex MRLs are based on scientific evaluations by expert panels that constitute the Joint FAO/WHO Meeting on Pesticide Residues (JMPR). These panelists estimate an acceptable daily intake for a pesticide and expected level of residue remaining in food when the pesticide is used according to good agricultural practice. The goals of the CCPR are not being fully achieved. Governments are generally not accepting Codex MRLs; instead, technical and procedural aspects of the JMPR and CCPR process are being criticized. The CCPR is responding to valid criticisms of the process; however, governments may still lack the will to seek harmonization of pesticide limits for food in international trade. Overcoming this problem will be difficult, but not impossible. A plan of action is proposed that allows countries to selectively accept Codex MRLs, increase the number of chemicals in the JMPR/CCPR system for evaluation, and be responsive to both their consumers and their food producers without compromising national health and safety standards and competitive trade advantages. PMID- 1438995 TI - Perspectives on formaldehyde toxicity: separating fact from fantasy. AB - Formaldehyde (IUPAC name, methanal) is one of the simplest, most ubiquitous molecules in our environment and troposphere. Exposure to large amounts of formaldehyde can produce a variety of respiratory and dermatologic problems in humans, in both the home and the workplace. However, in spite of anecdotal reports on formaldehyde-induced illness over the past 20 years there is a paucity of data regarding its potential as either an allergen or an antigen in humans. In addition, many of our current impressions about formaldehyde are based on studies of dubious scientific validity. In this review, we discuss the biological and chemical properties of formaldehyde and its presence in materials which we come in contact with, and finally attempt to put in perspective our current understanding of the detrimental effects of formaldehyde on our health, or lack thereof. There is no evidence at present that formaldehyde causes immunological diseases. Finally, and unfortunately, many of the studies have drawn invalid conclusions and are based on poorly controlled anecdotal observations. PMID- 1438996 TI - An alternative to the USEPA's proposed inhalation reference concentrations for hexavalent and trivalent chromium. AB - The passage of the Clean Air Act Amendment of 1990 reflects a growing public concern over human exposure to air toxics. The EPA is currently identifying inhalation reference concentrations (RfCs) to be used as risk criteria for determining whether existing or predicted ambient levels of chemicals are above acceptable concentrations. This paper evaluates the risk assessment methods used by the EPA to develop the recently proposed RfC (0.002 micrograms/m3) for both trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)]. Based on our evaluation, these RfC values do not appear to have been developed in accordance with standard Agency procedures or classic toxicology methods for setting RfCs. In particular, the "key" study used by the EPA [E. Lindberg and G. Hedenstierna (1983) Arch. Environ. Health 38, 367-374] as the basis for their proposal is not appropriate because it examined only the effects of exposure to chromic acid mist [Cr(VI)], even though most environmental exposure is to Cr(VI) and Cr(III) as a dust. The health hazards of Cr(VI) as an acid mist are significantly different from those associated with Cr(VI) as a dust. Further, the EPA's key study did not evaluate exposure to Cr(III), the toxicity of which is significantly different from both particulate Cr(VI) and chromic acid mist. Finally, the uncertainty factors used to account for data gaps were unusually high, thus providing RfC values equal to or below most naturally occurring environmental levels and standard analytical limits of detection. In this paper, we propose alternative RfCs for Cr(VI) as chromic acid mist and for Cr(VI) as a dust. Based on the Lindberg and Hedenstierna study, we derived an RfC of approximately 0.12 micrograms/m3 for chromic acid mist. An RfC of 1.2 micrograms/m3 is recommended for particulate Cr(VI) based on animal studies that evaluate long-term inhalation exposure to Cr(VI) dust. Due to its low toxicity, an RfC for Cr(III) is not warranted. PMID- 1438997 TI - Thyroid follicular cell carcinogenesis: results from 343 2-year carcinogenicity studies conducted by the NCI/NTP. AB - The National Toxicology Program data base on 343 mouse and rat carcinogenesis studies was reviewed to determine the frequency of and relationship between hyperplastic and neoplastic follicular lesions of the thyroid gland. The frequency of chemically related lesions in the thyroid was also compared to neoplastic lesions in the liver to investigate a possible correlation. The percentage of studies observed to have positive or equivocal chemically related thyroid proliferative lesions was rats: male, 14%, female, 11%; mice; male, 8%; female, 9%. When positive in one sex for a given chemical, there was a 60-80% chance of it being positive in the other sex of the same species, although interspecies correlation was not as strong. Thyroid follicular cell neoplasia without hyperplasia was uncommon in mice but was common in rats. Chemicals that caused thyroid proliferative changes were more likely (P less than 0.05) to produce liver neoplasms (both within and between species) than were chemicals causing no thyroid changes. However, this correlation was far from perfect, with many chemicals producing thyroid proliferative lesions, but not liver neoplasms and vice versa. This suggests that universal correlations are not supportable by the data and that individual chemicals should be evaluated on a case-by-case basis. PMID- 1438998 TI - Role of maternal toxicity in assessing developmental toxicity in animals: a discussion. AB - The belief that any drug or chemical, when administered at a high enough dose, can be expected to produce fetal malformations is not consistent with the facts. However, the stress associated with maternally toxic doses can be expected to result in associated, often transient, fetal abnormalities that may not be the result of deviant organogenesis. Sometimes the toxicity toward the pregnant animal, including her embryos/fetuses since they are hardly in a sanctuary, is severe enough to result in resorption of the embryo or abortion of the fetus. Thus, it is possible that the embryolethality and other indications of developmental toxicity, produced by some drugs and chemicals, may be the result of a mechanism(s) other than selective toxicity toward the embryo. Also, some test materials have been shown to affect maternal homeostasis, thereby disrupting support to the embryo, without causing significant overt toxicity to the embryo or dam; e.g., the endocrine system of the dam is altered. Routine testing has thus far revealed a relatively limited number of true teratogens, although a large number of drugs and chemicals have resulted in fetal effects such as developmental variations when administered at doses that approach lethal levels. Such effects on the fetus should be expected when the maternal animals are stressed by the high dosages usually employed. A better understanding of the etiology and biological relevance of the embryo/fetal deviations often seen in developmental toxicology studies might help to avoid the sometimes unjustified withholding of potentially useful drugs and chemicals from the marketplace. PMID- 1438999 TI - An analysis of the U.S. Environmental Protection Agency neurotoxicity testing guidelines. AB - Few of the more than 65,000 chemicals listed in the Environmental Protection Agency (EPA) inventory have been tested for neurotoxicity. The nervous system may be especially vulnerable to toxicants because many compounds can cross the blood brain barrier and induce irreversible damage. Additionally, the young, the elderly, and other sensitive populations may be particularly susceptible to neurotoxic injury. The EPA has developed guidelines including neurobehavioral, neuropathological, and neurochemical tests for the identification of possible neurotoxicants. In the present review, tests included in the current EPA guidelines for neurotoxicity testing are described and evaluated. The main benefit of the tests is that regulators are familiar with them, thus facilitating interpretation. Additionally, validation data on these tests are available for many known neurotoxicants. These factors make it difficult to introduce new methods that may include in vitro and other techniques. The current in vivo tests can be costly and prolonged and can involve the use of many laboratory animals, making them inappropriate for generalized use on existing chemicals. It is suggested that alternative tests be incorporated for screening of large numbers of chemicals and that testing priority be given to chemicals on the basis of structure/activity relationships, lipophilicity, bioaccumulation, and extent of exposure. PMID- 1439000 TI - [The significance of the AMES and the NTM systems to determine the prognosis in patients with differentiated cancer of the thyroid]. AB - The author considers that the AMES and TNM systems are reliable in determining the prognosis in patients with well differentiated thyroid carcinoma. In low risk patients with tumors less than 2 cm in diameter, total lobectomy and hormonal suppression are sufficient therapy. In other patients, total or subtotal thyroidectomy are advisable to facilitate further control and therapy. Total or subtotal thyroidectomy should always be done in high risk patients. Metastases to the regional lymph nodes are not an important risk factor, but they should always be excised. Radioactive iodine therapy is not useful for low risk patients. PMID- 1439001 TI - [Cloning of kDNA minicircles in different species of Leishmania and its use as probes for diagnosis]. AB - The present study describes the cloning procedure for fragments of kinetoplast DNA minicircles from different Leishmania species and its use for detecting the presence of these parasites. Our methodology was as follow: the DNA of the kinetoplast from Leishmania mexicana amazonensis and Leishmania braziliensis panamensis was extracted, purified and digested with the enzyme Dra I. These fragments were cloned in the site for Hinc II in the plasmid pKS. E. coli was the bacterial strain used for transforming and amplifying the cloned fragments; the selection was carried out in LB medium supplemented with ampicillin. With the clones suspected to be positives we run a Southern blot and total kDNA, from each Leishmania species, was used as hybridization probe. Finally, the cloned purified fragments were tested as diagnostic probes against kDNA from eleven different species of Leishmania and one of Trypanosoma cruzi parasites. After cloning, transforming, amplifying and selecting, we obtained two probes of fragments of kDNA minicircles: one from L. m. amazonensis and the other from L. b. panamensis. Both probes showed high sensitivity for diagnosing cutaneous Leishmania complexes (Mexicana or Braziliensis); however, we observed a low grade crossreaction between some species belonging to the same complex. It is necessary to continue studies in order to obtain subfragments of these probes with a higher grade of specificity at the level of species and subspecies. PMID- 1439002 TI - [Fetal cardiocirculatory physiology]. AB - The authors analyzed the physiology of fetal circulation and its variations during hypoxia. They propose a systematic approach which would allow early diagnosis of hypoxia during its initial phases, as a contribution in order to reduce perinatal morbidity and mortality. PMID- 1439003 TI - ["Cholos de Cocle": determination of their racial mixture and genetic origins]. AB - We have found, in this first genetic study of a supposedly admixed Panamanian population, that the cultural group known as "cholos of Cocle" constitute a trihybrid mixture, whose genetic pool has the following composition: 44% Amerindian, 38% Caucasoid and 18% Negroid. Similarly, we have detected Amerindian genes, such as LDHB--Gua and TFchi, in proportions that relate this population with the extant Ngawbe (Guaymi). Nevertheless, the very high frequency of variant PEPA--KUN seems to indicate the genetic contribution of Amerindian populations from Eastern Panama, possibly from the extinct indigenous group cueva. This variant is frequently found among the present-day Kuna, but has not been detected among Nagawbe and Bugle. PMID- 1439004 TI - [Laparoscopic pelvic lymphadenectomy in patients with cancer of the prostate]. AB - Laparoscopic pelvic lymphadenectomy is a new procedure to determine the propagation grade of Prostatic adenoma and the treatment to recommend. It is a satisfactory procedure for the diagnosis, with minimal morbidity. It is described our early experience in Panama, 6 patients and 51 lymph nodes removed. PMID- 1439005 TI - [Acute epiglottitis in adults]. AB - The author presents the clinical history of 14 patients, from 21 to 48 years of age, 10 men and 4 women, with a final diagnosis of acute epiglottitis who were hospitalized at Gorgas Army Hospital or at the San Fernando Clinic. All the patients had pharyngitis and dysphagia, a few with nasal voice, stridor and difficulty breathing, as the chief complaint. All the patients were initially intubated orally for diagnostic purposes and immediately after nasotracheal intubation was done until the patient improved in 2 or 3 days (one patient remained intubated for 5 days). All patients were kept in the Intensive Care Unit and were treated with Ampicillin and Chloramphenicol IV and lately with a second generation cephalosporin (Cefamandole). The patients allergic to Penicillin were treated with Clindamycin and Chloramphenicol. Corticosteroids were not used in any of the patients. There were no sequelae and none of the patients expired. PMID- 1439006 TI - [Changes in the pain produced by the peripheral venous injection of propofol when it is combined with lidocaine or fentanyl]. AB - The author studied the use of intravenous Propofol for the relief of pain. He demonstrated that Propofol and 10 mg of Lidocaine intravenously decreased moderate or severe pain from 31.6% to 9% and that increasing the dose of Lidocaine did not significantly decrease the pain further. Fentanyl did not produce a statistically significant further diminution of the pain from the level of relief obtained with Propofol. PMID- 1439007 TI - [Prevalence of Helicobacter pylori in patients with gastric cancer in Panama]. AB - Cancer of the stomach is the second in incidence in Panama after the cancer of the prostata. It is studied now the incidence of infection due to Helicobacter pylori in patients with gastric carcinoma. It seems to be a significative relationship between the prevalence of gastric carcinoma and H. pylori infections. This observation is important because by the similar therapeutic implications in virus DNA hepatitis type B and hepatoma. PMID- 1439008 TI - [Isolation and identification of Gardnerella vaginalis in women with symptoms of bacterial vaginosis]. AB - 70 samples of vaginal secretions were collected from women with bacterial vaginosis syndrome, that were attended in Nuevo Veranillo' Health Center. All samples were tested in order to determinate the presence of amine and to Gram'methods stain to observe the morphologic characteristics of the "Clue" cells (epithelial cells with adhered bacteria). Samples were cultured in a selective media of blood agar in Columbia base with colistine and nalidixic acid, and incubated in an environment of CO2 at 37 degrees C. Tests of oxidase, catalase, glucid fermentation, hippurate hydrolysis and starch hydrolysis were made on the grown colonies. 27 out of 70 samples resulted in positive cultures for Gardnerella vaginalis, 11 to pregnant women and 16 to nonpregnant women; among these, 14 women used some kind of contraceptive methods as DIU or pill. PMID- 1439009 TI - [The propedeutic course given at the School of Medicine and the academic performance of the students that passed it]. AB - A report of the results of the Propedeutic Course in the Medical School of the University of Panama is informed. This course was established by the Academic Council, at the request of the Medical School, to diminish the registration form 280 to 180 students, taking into account the low academic performance of the students with the lowest grades in the Admission Process. The study showed that the correlation indices of the students in the Propedeutic Course and in the first regular semester was low. The study also showed that the number of students from the Propedeutic Course who repeated or were separated from the school, was higher than those from the regular semester. PMID- 1439010 TI - [Rosa Maria Britton and Jose Guillermo Ros-Zanet: outstanding people of the Panamenian literature]. PMID- 1439011 TI - Neoplastic and inflammatory processes of the peritoneum, omentum, and mesentery: diagnosis with CT. AB - Disease processes in the peritoneum, omentum, and mesentery occasionally are not recognized at radiologic examination. The authors have used computed tomography (CT) to categorize the radiologic appearances of the more common abnormalities into three basic patterns: (a) solid but relatively well-defined masses, (b) cystic-appearing masses, and (c) ill-defined or infiltrative processes. The most common solid masses to affect these anatomic regions are secondary neoplasms, which are associated with enhancement of the peritoneum on contrast material enhanced CT scans and, typically, ascites. The various cystic-appearing masses (including cystic lymphangioma, cystic mesothelioma, teratoma, and loculated ascites) and infiltrating masses (such as peritoneal mesothelioma, retractile mesenteritis, desmoid, and carcinoid) must be differentiated on the basis of clinical findings and additional imaging findings (eg, CT depiction of fat and calcium in teratomas and the radiating appearance of carcinoids). Although the CT appearances of some of the abnormalities overlap, classifying them by pattern is helpful in narrowing the range of the differential diagnosis. PMID- 1439012 TI - Clinical significance of pneumatosis of the bowel wall. AB - The presence of gas within the bowel wall is an uncommon condition that is typically first diagnosed by the radiologist. Although it is often seen on abdominal radiographs, computed tomography is more sensitive in demonstrating pneumatosis and its complications. There is a spectrum of disease states that produce this abnormality, ranging from the innocuous to the fatal. Its radiographic appearance is variable, particularly the location, extent, severity, and presence of pneumoperitoneum or portal venous gas. None of these imaging characteristics can be considered pathognomonic for the underlying cause of the pneumatosis. The radiologist must be aware of the different conditions associated with this entity, as well as their variable appearances. PMID- 1439013 TI - MR imaging of posterior fossa infarctions: vascular territories and clinical correlates. AB - Ischemic infarctions in certain vascular territories of the cerebellum and brain stem can produce some characteristic radiologic and clinical patterns. The cerebellum serves as a coordination center for the maintenance of equilibrium and muscle tone and refines the movements of the somatic muscles. The anatomy of the brain stem is extremely complex, and small infarcts can potentially be disastrous. MR imaging depicts the anatomy of the posterior fossa and infarcts in this region with greater accuracy than was previously possible. Familiarity with the vascular territories and patterns of infarction of the posterior fossa depicted with MR imaging and familiarity with the associated clinical symptoms of stroke in this region can help the radiologist recognize these infarcts and correlate clinical and radiologic findings. When patients are referred for MR imaging of the brain because of clinical findings suggestive of infarction, it may be useful to obtain coronal or sagittal views in addition to axial images to better depict the vascular distribution of a suspected ischemic lesion. PMID- 1439014 TI - Gadolinium-enhanced MR imaging of renal masses. AB - Preliminary reports indicate that gadolinium-enhanced magnetic resonance (MR) imaging is highly accurate for diagnosis of renal masses. The authors demonstrate the clinical utility of MR imaging for evaluating renal masses in 26 patients for whom contrast material-enhanced computed tomography (CT) was contraindicated or inadequate for diagnosis or staging. Nine patients had complex cysts, one had a perinephric hematoma, and 16 had a solid mass (three of which were benign). All patients underwent MR imaging before and after administration of gadopentetate dimeglumine. Multiple imaging techniques and sequences were used. All tumors and no cysts enhanced with gadolinium. Even though the three benign tumors enhanced, two were differentiated from renal carcinoma on the basis of other imaging features. Unenhanced MR imaging was accurate in staging of renal carcinomas, and use of gadolinium did not improve staging accuracy. Gadolinium-enhanced MR imaging is indicated when results of CT and sonography are indeterminate for malignancy and when contrast-enhanced CT is contraindicated because of renal failure or adverse reaction to iodinated contrast material. In this latter instance, MR imaging is useful for both diagnosis and staging. PMID- 1439015 TI - Misleading aggressive MR imaging appearance of some benign musculoskeletal lesions. AB - After plain radiography has been performed, magnetic resonance (MR) imaging is considered the modality of choice for the evaluation of suspected musculoskeletal lesions because of its exquisite sensitivity to changes in the signal intensity of marrow and soft tissue. That sensitivity, however, may lead to an overestimation of the aggressiveness and extent of some benign bone lesions, particularly in children. Such lesions include chondroblastoma, osteoid osteoma, eosinophilic granuloma, and stress fractures. Potentially misleading MR features commonly seen include prominent marrow edema, soft-tissue edema, and apparent mass effect adjacent to the bone lesion. Features that these lesions have in common that may explain the MR findings include associated inflammatory reactions caused by the lesions and their occurrence in childhood, when the periosteum is more loosely attached. Knowledge of the potential pitfalls encountered with MR imaging may help explain the discrepancy between the radiographic and MR appearances of these benign lesions and avoid misplaced reliance on MR imaging for a diagnosis. Radiography remains the single most valuable modality in determining a differential diagnosis for bone lesions. PMID- 1439016 TI - Effect of poor control of film processors on mammographic image quality. AB - With the increasingly stringent standards of image quality in mammography, film processor quality control is especially important. Current methods are not sufficient for ensuring good processing. The authors used a sensitometer and densitometer system to evaluate the performance of 22 processors at 16 mammographic facilities. Standard sensitometric values of two films were established, and processor performance was assessed for variations from these standards. Developer chemistry of each processor was analyzed and correlated with its sensitometric values. Ten processors were retested, and nine were found to be out of calibration. The developer components of hydroquinone, sulfites, bromide, and alkalinity varied the most, and low concentrations of hydroquinone were associated with lower average gradients at two facilities. Use of the sensitometer and densitometer system helps identify out-of-calibration processors, but further study is needed to correlate sensitometric values with developer component values. The authors believe that present quality control would be improved if sensitometric or other tests could be used to identify developer components that are out of calibration. PMID- 1439017 TI - Receiver operating characteristic curves: a basic understanding. AB - Receiver operating characteristic (ROC) is one form of an objective measurement that can be used to compare newer imaging technologies against human observer performance (the ability of the expert radiologist). Use of ROC curves allows one to account for a continuum of radiologic interpretations when calculating sensitivity and specificity for an imaging modality and avoids the inaccuracies that arise from assuming that imaging findings are absolutely normal or abnormal. An ROC curve is generated by plotting sensitivity on the y axis as a function of [1-specificity] on the x axis for a continuum of diagnostic criteria. ROC curves allow visual analysis of the trade offs between the sensitivity and the specificity of a test with regard to the variable diagnostic criteria used by radiologists. Because ROC curve analysis is gaining wide acceptance in medical literature, an explanation of ROC methods with the use of simple examples is necessary to increase the knowledge and understanding of practicing radiologists. PMID- 1439018 TI - Congenital and acquired orthopedic abnormalities in patients with myelomeningocele. AB - This article presents a radiologic review of the spectrum of acquired and congenital orthopedic abnormalities found in patients with myelomeningocele. These abnormalities are caused predominantly by muscle imbalance, paralysis, and decreased sensation in the lower extremity. Iatrogenic injury, such as a postoperative tethered cord, may also cause bone abnormalities. Selected images were obtained from more than 800 children. Important entities presented include spinal curvatures such as kyphosis, scoliosis, and lordosis; subluxation and dislocation of the hip, coxa valga, contractures of the hip, and femoral torsion; knee deformities; rotational abnormalities of the lower extremity and external and internal torsion; ankle and foot abnormalities such as ankle valgus, calcaneus foot, congenital vertical talus (rocker-bottom deformity), and talipes equinovarus; and metaphyseal, diaphyseal, and physeal fractures. Familiarity with congenital abnormalities and an understanding of the pathogenesis of acquired disorders in patients with myelomeningocele are essential for proper radiologic interpretation and timely therapy. PMID- 1439019 TI - Confidence levels in diagnosis: what can we afford? PMID- 1439020 TI - Congenital malformations of the cervicothoracic lymphatic system: embryology and pathogenesis. AB - Familiarity with the embryology of the lymphatic system is helpful in understanding the pathogenesis and radiologic appearance of lymphangiomas of the cervicothoracic region. By considering anatomic location and radiologic appearance, one can predict the type of lymphangioma present, the primordial lymph sac from which the malformation arose, and when it formed in embryonic life. Cystic hygromas are composed of large, dilated lymphatic spaces. They form when a primordial lymph sac fails to reestablish communication with the central venous system from which it arose. These lesions may also result from an aberrant bud arising from a primordial lymph sac. Cavernous and capillary lymphangiomas are composed of smaller lymphatic channels. They form from abnormally sequestered buds of the developing lymphatic mesenchyme responsible for the fine meshwork of terminal branches in the periphery of the embryo. Their growth may be inhibited by the relatively tougher tissues in the periphery (eg, skin and muscle) compared with the relatively loose fatty connective tissue in which cystic hygromas form. Not only can all types of lymphangioma occur in one lesion, but lymphatic and vascular malformations may also coexist. PMID- 1439021 TI - Imaging manifestations of pleural tumors. AB - Although radiologic assessment of pleural tumors may be accomplished with several imaging modalities, the standard noninvasive techniques include chest radiography and computed tomography (CT). These examinations may be supplemented with magnetic resonance imaging and occasionally with ultrasound. Depending on the location, size, and underlying histologic features, pleural tumors may produce a spectrum of findings. CT is particularly useful in defining the location and extent of these masses. The authors present a review of basic pleural anatomy and imaging features of both benign and malignant pleural neoplasms. The pleural may be involved by one of several primary or metastatic tumors. Specific cell types are diffuse malignant mesothelioma (the most common plain radiographic findings are unilateral pleural effusion and pleural thickening), localized fibrous tumor (circumscribed, spherical or ovoid, noncalcified lesions arising in the pleural surface), metastatic disease (radiographic findings may mimic those of malignant mesothelioma), and uncommon neoplasms including thymoma and lymphoma. Among these various pleural tumors, metastatic disease represents the most common neoplasm. PMID- 1439022 TI - From the archives of the AFIP. Leiomyosarcoma of the retroperitoneum and inferior vena cava: radiologic-pathologic correlation. AB - Leiomyosarcoma is the second most common primary retroperitoneal tumor in adults. Retroperitoneal leiomyosarcoma exhibits three major growth patterns: (a) completely extravascular (extraluminal) (62% of cases), (b) completely intravascular (intraluminal) (5% of cases), and (c) extra- and intraluminal (33% of cases). The usual clinical manifestation is a large abdominal mass. Intraluminal leiomyosarcoma may be accompanied by symptoms referable to venous thrombosis. The variable gross features and potential for intravascular extension result in various radiologic appearances, the most common being a large, partially necrotic soft-tissue mass in the retroperitoneum with or without extension into the inferior vena cava. Computed tomography and magnetic resonance imaging typically show a nonfatty, necrotic retroperitoneal mass and a vascular component when it is present. Ultrasound and angiography may also be useful, especially if vascular involvement is suspected from other imaging studies. Treatment of choice is surgical excision, which is frequently impossible due to the invasiveness of the tumor. Prognosis is related to extent of invasion and the adequacy of resection. Long-term prognosis is poor, and most patients die of local recurrence or distant metastasis. PMID- 1439023 TI - Radiation dose in CT. AB - The energy deposited in the patient by the rotating x-ray beam in computed tomography produces more uniform absorbed dose values within the section of imaged tissue than those produced in conventional radiologic procedures. The dose values within a specific section are determined by factors such as voltage, current, scan time, scan field, rotation angle, filtration, collimation, and section thickness and spacing. For routine dose determinations, a pencil ionization chamber is usually employed with a plastic phantom. Dose for a specific patient can be determined with thermoluminescent dosimeters placed on the patient. Multiple-scan procedures normally increase the dose in a specific section by less than a factor of two. Typical multiple-scan average doses are in the range of 40-60 mGy for head scans and 10-40 mGy for body scans. Integral dose, however, is directly proportional to the number of sections in an examination. When examination factors are changed to reduce dose, the image noise increases. An optimum protocol is one that results in a balance between dose and image quality. PMID- 1439024 TI - Ultrasound case of the day. Mucocele of the appendix. PMID- 1439025 TI - General case of the day. Thymolipoma. PMID- 1439026 TI - Pediatric case of the day. Neurenteric cyst without associated vertebral anomalies. PMID- 1439027 TI - [Coxa vara in children. Apropos of 28 cases]. AB - Infantile coxa-vara is an infrequent lesion and two etiologic factors have been recognised: mechanical and genetic. As in Blount's disease, the same populations (black and scandinavian people) are usually affected. Twenty eight patients with 42 infantile coxa vara were reviewed. The diagnosis was often late. The radiographs showed the decrease of the neck-shaft angle and the signs of cervical dystrophy. The aggravation of the coxa vara is usual and pseudarthrosis or osteo arthritis can be observed. Thirty six femoral valgus sub-trochanteric osteotomies were done. The results were best when the surgery was done before the age of 9 years. When the surgery was done later, an epiphysiodesis of the greater trochanter was associated to the femoral osteotomy if the epiphyseal cartilage was fused. Langenskiold's osteotomy was used only when the neck-shaft angle was lower than 80 degrees. The results were evaluated according to the neck shaft angle and the morphology of the femoral head: 22 very good and good, 11 fair and 3 bad results were noted. PMID- 1439028 TI - [Arthroscopic internal meniscectomy in patients over 55 years of age. Results over more than 4 years]. AB - Fifty-one meniscectomies by arthroscopy were realised on patients of more than 55 years of age between 1981 and 1986. Twenty-four patients were reviewed after at least 4 years of follow up, 12 of them after a 7.5 years follow up. 21 results were noted as functionally very good or good, 3 were poor. The radiological analysis of femoro-tibial compartments in comparison with the non operative side showed a clear pejorative difference in one case, moderate in 5 without incriminating the morphological type. If the quality of result does'nt correlate with age, it was'nt the same for the type of lesion seen during arthroscopy, the best results after arthroscopic meniscectomies were seen in traumatic lesions occurring on normal menisci or on degenerative ones. The authors concluded that medial meniscectomy in patients older than 55 years is justified in precise indications: a known traumatism or also acute medial pain, or speedy with normal or subnormal X-ray and after a positive arthrography. PMID- 1439029 TI - [Hallux valgus: the McBride procedure or subcapital osteotomy?]. AB - The authors compared the long term follow-up (mean duration 19 years) of 96 patients operated on for hallux valgus, 52 by the McBride procedure, 46 by a Hohmann procedure. Clinical results considered 4 criteria: deformity, pain, mobility and satisfaction. Dorsoplantar weight bearing X-ray compared anatomical results. This study showed that patients were subjectively more satisfied after McBride operation (p = 0.0001) even if the deformity was radiologically better reduced by osteotomy (p = 0.006). This discrepancy between subjective and radiologic results was related to the fact that X-rays represent only the static morphologic reflect of a more complex pathologic entity: radiology can only partly explain the functional discomfort of the patients. The modified McBride procedure was better suited to patients presenting a painful HV. Osteotomy was more suited to bunions causing little pain. Indications for each of these procedures should be based more on patient's history and clinical examination than on X-rays. PMID- 1439030 TI - [Ulnar translocation of the carpus after surgery of the rheumatic wrist. Review of 54 cases]. AB - Fifty-four rheumatoid wrists, on which synovectomy and caput ulnar resection had been performed, were re-examined 1 to 8 years after the operation (average follow up: 3.8 years). The clinical results were good, and the wrists pain-free in 91 per cent of cases, with a low rate of synovitis recurrence (4 per cent), and 88 per cent of the mobility in the sagittal plane was preserved. Radiological examination revealed a moderate aggravation of carpite over the years. This evolution was not linked, however, to the fact that no intracarpal synovectomy was performed in our series since a similar evolution has been reported by authors who carry out this synovectomy. Ulnar translocation of the carpus was commonly measured in relation to the ulna axis, but as the latter tends to get into a more medial position after the surgery this analysis was incorrect. Ulnar translocation should be measured in relation to the axis of the radius, which remains in the same position. Studied in this way, the average translocation in this whole series was 2 mm. A comparative study of the operated wrist and the non operated wrist in 27 patients revealed a significant aggravation (p < 0.2) of ulnar translocation of the carpus at radiological stages 2 and 3. This translocation remained however minimal. A combined transfer of the extensor carpi radialis brevis or longus onto the extensor carpi ulnaris did not slow down ulnar translocation of the carpus, but the other hand it improved the correction of radial deviation of the carpus and ulnar deviation of the fingers. PMID- 1439031 TI - [Total denervation of the wrist. Apropos of 50 cases]. AB - Fifty patients who underwent a total denervation of the wrist were reviewed after an average of 5 years post-operatively. The main aetiology was diffuse osteo arthritis secondary to scaphoid nonunion (44 per cent) and Kienbock's disease, stage IV (22 per cent). This resulted in pain and functional disability. Another surgical procedure was carried out in 40 per cent of patients. Post-operative complications included one painful neuroma and 3 patients complained of radial nerve paraesthesia. Pain was improved in 36 of the 50 patients with an average score of 72 over a scale of 100. There was no significant change in power or range of movement. PMID- 1439032 TI - [Bipolar endoprosthesis in fractures of the femoral neck. Apropos of 201 cases, 116 after a 6-year follow-up]. AB - We report our experience with 201 SEM bipolar prostheses used to treat femoral neck fractures in patients with a mean age of 70 years and a mean follow-up of 57 months (median 75 months). Clinical outcome was favorable with 94 per cent satisfactory results (very good and good). Femoral complications requiring reoperation (conversion to total hip replacement) occurred in 2.2 per cent of cases. Among the 163 patients for whom roentgenographic data were available, 5 (3.6 per cent) developed evidence of acetabular wear but remained symptom-free and did not require reoperation. As compared with Moore's prosthesis, the SEM bipolar prosthesis seems to provide substantially better clinical and roentgenographic results. For the treatment of femoral neck fractures, total hip replacement seems to provide results comparable to those reported here but requires a more sophisticated operative technique and carries a greater risk of subsequent dislocation. Two factors prevent the widespread use of the bipolar prosthesis at present: the need for femoral grouting which carries a well documented risk of hemodynamic complications, and the higher cost of the device. PMID- 1439033 TI - [Embolization of the circumflex femoral artery for recurrent hemorrhage after total hip arthroplasty. Apropos of a case]. AB - Reoperation of an haemorrhagic complication after total hip arthroplasty may be not efficacious when, as in the case report, bleeding's origin is not found. The vital prognosis can be quickly set in action and then the arterial embolization be the swift and efficacious solution. The selective arteriography that precedes it allows to locate the bleeding's origin, to estimate gravity of leak and to set indication of embolization. So it is fitting to think of this therapeutic solution that may avoid new operation and new failure. PMID- 1439034 TI - [Necrotizing fasciitis of the upper limb: a case]. AB - Necrotizing fasciitis is a rare form of anaerobic infection, quite different from gas forming gangrene: it affects the skin, the cellular tissue, the fascia; it doesn't diffuse in depth to the muscles and doesn't produce gas. Its microbic agents vary from haemolytic streptococcus to anaerobic bacteria in synergy. It rapidly spreads into a massive necrosis and can in a week's time lead to death by toxic shock. It spreads locally to large cutaneous areas eventually leading to the necessity of amputations. A joint treatment must be started with extreme urgency: extensive surgical excisions of all necrotic teguments, and medical treatment consisting of correcting metabolic troubles and antibiotherapy. This difficult treatment can save the patient, but it involves great loss of cutaneous and subcutaneous substance leading to local problems which are similar to serious burns, then to problems of reconstruction. An open fracture of the elbow led to an observation. A review of the literature sets out the different forms and complications. PMID- 1439035 TI - [Fatigue fracture below the internal tibial plateau after locked intramedullary nailing]. AB - The authors present a case of stress fracture of the medial condyle of the tibia following intramedullary nailing with distal locking. This complication, which appeared two years after the surgical procedure and one year after the removal of the nail, has not yet been described in the literature. The patient was a young man without any excessive physical load. The presence of the intramedullary nail was accompanied by a bone clearness in the medial part of the superior epiphyseo metaphyseal level of the tibia. PMID- 1439036 TI - [Immunomodulation in oncology]. PMID- 1439037 TI - [Systemic amyloidosis: clinico-pathologic study of 69 cases]. AB - A series of 69 cases of systemic amyloidosis is discussed (12 primaries; 7 due to myeloma; 44 reactive; 5 due to familiar mediterranean fever and 1 portuguese familiar polyneuropathy) in which their clinical aspects, topographical distribution of the deposit and histochemical characteristics are studied using the potassium permanganate technique. According to sings and symptoms of presentation and topography there is a remarkable overlapping in the five types of amyloidosis. Only macroglossia was more frequent in primary amyloidosis (p less than 0.001). However the potassium permanganate technique can help in the classification. Considering the first clinical diagnosis. 83% of primary amyloidosis and 100% of amyloidosis due to myeloma, were resistant to permanganate. 84% of reactive amyloidosis and 100% of familiar mediterranean fever, were sensitive. The only case of portuguese familiar polyneuropathy showed resistance. PMID- 1439038 TI - [Clinical experience with zidovudine in patients with acquired immunodeficiency syndrome. Analysis of 117 cases. Grupo Andaluz para el Estudio de las Enfermedades Infecciosas]. AB - In order to assess the efficacy and the toxicity of zidovudine in AIDS patients, we have studied, prospectively, 117 patients that were treated with this drug, in several andalusian hospitals between January 1988 and June 1990. Initial dose of the drug was 200 mg every 4 hours. Mean survival was 100% at 6 months and 66.5% at 23 months. Survival at 19 months was higher in ADVP (77%) than in non-ADVP (48%). A positive influence on weight. Karnofsky index and number of opportunistic infections during the six first months of treatment was recorded, benefit that was lost progressively from that moment onwards. Main adverse effects were hematological, 10.1% of the patients requiring transfusions due to hemoglobin lower than 6.5 gr%. The more frequent cause to stop therapy was severe neutropenia (less than 500 neutrophils per mm). We consider that the beneficial effect of zidovudine is only transient, diminishing gradually when the treatment is prolonged. At present doses adverse effects are moderate not being present in most of the patients. PMID- 1439039 TI - [Primary pulmonary hypertension. Clinico-pathologic analysis]. AB - We present a case of primary pulmonary hypertension, confirmed by open lung biopsy. The interest of the case resides in the microscopic study of the specimen, and the patient's prognosis is discussed. The physiopathology of the disease is reviewed and the palliative therapeutic measures that can be adopted. PMID- 1439040 TI - [Atypical radiologic manifestations of Pneumocystis carinii pneumonia]. AB - Pneumonia due to Pneumocystis carinii (PC) is characterized, in most cases, by the existence of infiltrates of interstitium or bilateral interstitium-alveolar type on the thorax radiography. However atypical radiological findings associated with this type of opportunistic infection are being described more and more frequently. We present two patients with Acquire Immune Deficiency Syndrome (AIDS) and pulmonary infection due to PC, with very unusual radiological findings. First patient showed multiple pulmonary cavitated nodules; the other a cavitated infiltrate in superior right lobule. Clinicians dealing with AIDS patients must be familiar with this unusual radiologic findings associated with PC in order to avoid diagnostic mistakes. PMID- 1439041 TI - [Autoimmune hemolytic anemia and carcinoma of the larynx: an exceptional association]. AB - The purpose of this annotation is to review the serological data to diagnosis, severity of the disease, treatment and prognosis of the autoimmune haemolytic anemia (AIHA) associated with carcinoma. A patient with AIHA and larynx carcinoma is presented. PMID- 1439042 TI - [A 19-year-old woman with pleural mass and effusion in left hemithorax]. PMID- 1439043 TI - [Convulsions and rapidly progressive neurologic deterioration]. PMID- 1439044 TI - [Protein nutrition and physical activity]. AB - The relationship between physical exercise and diet in order to optimize performance is getting growing interest. This review examines protein needs and protein intakes as well as the role of protein in the body and the metabolic changes occurring at the synthesis and catabolic levels during exercise. Protein synthesis in muscle or liver, amino acids oxidation, glucose production via gluconeogenesis from amino acids, etc., are modified, and consequently plasma and urinary nitrogen metabolites are affected. A brief comment on the advantages, disadvantages and forms of different protein supplements for sportsmen is given. PMID- 1439045 TI - [Magnesium. The fourth drug in the treatment of asthma?]. PMID- 1439046 TI - [Primary antiphospholipid syndrome associated with Sneddon syndrome]. PMID- 1439047 TI - [The use of antidigoxin antibodies]. PMID- 1439048 TI - [Cushing's syndrome caused by black adrenal gland adenoma]. PMID- 1439049 TI - [In vitro T-cell response against HBsAg (p25)]. PMID- 1439050 TI - [Asymptomatic rhabdomyolysis in a hunting day]. PMID- 1439051 TI - [Intrathoracic hemangioma of the intercostal muscles]. PMID- 1439052 TI - [Anaphylactoid Schoenlein-Henoch purpura caused by midecamycin?]. PMID- 1439053 TI - [Severe adverse reaction during treatment with rifampicin]. PMID- 1439054 TI - [Meningococcemia and human immunodeficiency virus infection]. PMID- 1439055 TI - [Acute post-varicella++ cerebellar ataxia]. PMID- 1439056 TI - The cholera epidemic in Ecuador: towards an endemic in Latin America. AB - We present an epidemiological study of the first wave of cholera in Ecuador in 1991. One month after the 7th cholera pandemic hit the Pacific coast of Peru, the disease reached the coast of Ecuador and spread to the rest of the country within a few weeks. One year later, 46,320 cases have been notified, giving an incidence of 481 cases per 100,000 inhabitants. The overall mortality rate has been low (697 deaths, i.e. 1.50%), although there have been large differences between the various provinces: in the Andes (Sierra), for example, rates above 8% have been recorded. The first wave peaked about eight weeks after the first case, with 3400 new cases per week throughout the country. This was followed by a gradual decrease towards a baseline of 250-500 new cases per week. A resurgence was observed in most coastal and Andean provinces from November 1991 onwards. The kinetics of the epidemic are compatible with an endemic implantation of the disease in Ecuador, as is probably the case in the entire intertropical Pacific coast region of Latin America. From the data presented, the latin-american episode of the 7th pandemic starting on the Pacific coast, is characterized by a very high attack rate and a low mortality rate as compared to Africa, and the unexpected involvement of populations living on the high Andean plateaux. It is probable from the results collected in Ecuador that cholera will become endemic in Latin America. PMID- 1439057 TI - [Case control studies in investigation of food-borne infection outbreaks. Study of their utilization in France]. AB - Among the 251 foodborne outbreaks investigated by public health officers in France in 1989, 62 (25%) used a case-control study to identify the responsible food. This survey aims to analyse the results of these 62 investigations. Thirty eight (61%) investigations found the responsible food(s); 10 investigations (16%) lacked power because of the small size of the population studied, but allowed to suspect the food with the highest odds ratio; 13 investigations (21%) gave results inconsistent with bacteriological studies or with hypothesis generated by the descriptive study: in 5 of it, food origin is questionable and in 8 investigations, methodological errors are likely. We could not conclude for one study. Among the surveys with case-control studies, 74% identified the food responsible with bacteriological or epidemiological confirmation, as opposed to 17% of other surveys which had only bacteriological confirmation. This study allowed us to give recommendations on the management of investigation and the interpretation of results to improve the efficiency of this practice. PMID- 1439058 TI - [Trends in mortality characteristics in Aids in France 1983-1990]. AB - From 1983 to 1990, the number of AIDS deaths in France (8119 deaths overall), increased substnatially but the annual rate of progression has fallen since 1987 (+35% in 1990). The socio-demographic characteristics of the deaths remained quite steady with the exception of the proportion of subjects living in Paris which decreased. The proportion of AIDS deaths out of all deaths is still low for the entire population (5 deaths out of 1000 in 1990) but appears important in some sub-groups. In 1990, AIDS represents for the 25-34 years old group, 12 deaths out of 100 for males and 7 deaths out of 100 for females and for the 25-44 years old group, 15 deaths out of 100 for nonmarried males and 4 deaths out of 10 for males working in an information or artistic profession. Furthermore, it accounts, in 1989, for the third of the deaths of males between 25 and 44 years living in Paris. The analyse tends to show that there is not an important under declaration of AIDS deaths in France. PMID- 1439059 TI - [Estimate of seroprevalence of HIV infection in Belgium using the back calculation method]. AB - An estimation of HIV seroprevalence in Belgium in June 1990 was made by the "back calculation method". The theoretical calculation of the number of virus carriers gave a range of values from 5,750 to 16,800 carriers. The upper part of this range seems to be more consistent with data from epidemiologic monitoring (range of values from 8,900 to 16,800 carriers). HIV prevalence rate in Belgium in June 1990 would is estimated between 0.9/1000 and 1.7/1000. The detection rate of the infection among HIV positives individuals should be at least 34%. PMID- 1439060 TI - A randomised 2 x 2 factorial design to evaluate different smoking cessation methods. AB - A study with a 2 x 2 factorial design was performed to evaluate the effectiveness of acupuncture, of nicotine gum and the effect of the association on smoking cessation. After a one-year follow-up period, the success rates were in the same order of magnitude for nicotine gum (active treatment: 10%, placebo: 8%) group and for acupuncture (active treatment: 8%, placebo: 10%) group. PMID- 1439061 TI - [French-language adaptation of an evaluation test of knowledge meant for insulin dependent children: methodology and value for research in clinical practice]. AB - A measure of knowledge level of diabetic patients is useful in evaluating their educational needs as well as the impact of the educational programs specifically designed for them. The lack of such scales in French, led us to translate and validate an existing knowledge scale for diabetic children, the Test of Diabetes Knowledge (TDK) (Johnson et al.). After several translations and back translations, the 33 item scale was submitted to the staff members of a pediatric diabetology unit, to establish its content validity. An assessment the questionnaire was performed in a group of 49 children, aged 7.9 to 12.8 years. The mean duration of diabetes was 4.6 +/- 2.9 years and their scholastic level varied from 1st to 6th grades. Time spent in filling out the questionnaires was 12 to 25 minutes. Few missing values were noted. The reliability of the scale was excellent as shown by Cronbach's alpha coefficient: 0.83 for the overall scale, 0.72 for the general knowledge subscale (20 items) and 0.70 for the problem solving subscale (13 items). The level of correct responses was correlated with age and scholastic level (p < 0.0001), but not with sex, duration of diabetes, or HbA1c levels. This study shows that the French version of the TDK is a valid and reliable tool for measuring the level of knowledge in children and adolescents with diabetes. This scale provides the researcher and clinician with a tool that facilitates the performance of an educational diagnosis and the evaluation of educational programs based on the transmission knowledge. PMID- 1439062 TI - Mass sociogenic illness in a youth center. AB - In July, 1989, 63 (42%) of 150 children ages 4-14 years attending an outreach program at a youth center in Florida, but no employees, developed acute and rapidly resolving upper gastrointestinal symptoms 2 to 40 minutes after a prepackaged lunch. All ill children were sent to 3 local hospital emergency departments for evaluation. However, clinical evaluation was normal for all. Of 102 children who ate any prepackaged foods, 48 (47%) became ill compared to 1/19 (5%) for children who did not eat (rate ratio [RR] = 8.9; 95% confidence interval [CI]: 1.3-60.9). No employees ate any of the food items served. Consumption of sandwiches was associated with a moderate increased risk of illness (RR = 1.7, 95% CI: 1.0-2.9). The attack rate did not differ by age, but was greater for girls (39/56, 70%) than for boys (9/46, 20%; [RR = 3.6, 95% CI: 1.9-6.6]). Over 3,000 similar prepackaged meals from the same caterer were served in the same area of Florida that day. An inquiry in the area documented absence of similar symptoms elsewhere. Unopened meal samples tested negative for pesticide residues, heavy metals, staphylococcal toxin, or Bacillus cereus. We diagnosed the outbreak as mass sociogenic illness. Complaints of a bad tasting sandwich by the index case and possible staff anxiety about food poisoning may have contributed to the development of the outbreak. PMID- 1439063 TI - [Jackknife and bootstrap]. AB - The jackknife and the bootstrap are two non parametric methods which provide estimates- of the bias and the variance of an estimator, without any assumption about its statistical distribution. The jackknife is based on the observation of the estimator for subsamples, generally of size n-1, obtained from the original sample. The bootstrap is based on the observation of the estimator on size n samples drawn from the original sample. The two methods are presented, their principle is illustrated through their application to simple examples and to more complex epidemiological problems. PMID- 1439065 TI - [The Swedish system of epidemiological surveillance of congenital malformations]. PMID- 1439064 TI - [Evaluation of a screening program for breast cancer]. PMID- 1439066 TI - [Prevalence of coronary disease in patients with aortic stenosis]. AB - We analyzed a consecutive series of 188 patients, older than 44 years, with significant aortic stenosis, who underwent coronary arteriography (73 women and 115 men). There were 38 patients (20.2%) with coronary artery disease ( or = 50% reduction in the luminal diameter). Sixty-eight patients had typical angina pectoris, 52 atypical angina, and 68 did not have chest pain. We found to have coronary disease in 29.4%, 23.1% and 8.8% respectively. Sensitivity of typical angina to detect coronary disease was 52.6%, with an specificity of 68%, and a negative predictive value of 85%. Inclusion of atypical angina improved the sensitivity to 84.2%, and the negative predictive value to 91.2%, but lessened the specificity to 41.4%. Six patients among the 38 with coronary disease (15.7%), did not have chest pain, and 3 of them were younger than 60 years. We conclude that absence of angina is not enough to exclude coronary artery disease in patients 50 years old with aortic stenosis being considered for aortic valve replacement. PMID- 1439067 TI - [Captopril + hydrochlorothiazide versus captopril + nifedipine in the treatment of arterial hypertension in diabetes mellitus type II]. AB - Captopril is a suitable drug to treat high blood pressure in diabetic patients. This Angiotensin-Converting Enzyme Inhibitor (ACEI) is a vasodilator without tachycardia and saline retention. Furthermore, captopril is one of antihypertensive drugs with less adverse effects. It does not induce metabolic changes, improves glucose tolerance and brake the evolution of renal insufficiency. About 50-60% of patients are under control (DBP < 90 mmHg) with captopril monotherapy. In the present paper, were included 64 women and 16 men with diabetes mellitus and mild-moderate hypertension, I-II phase WHO. The average age (mean +/- S.D.) was 66.6 +/- 9.2 years. All patients were treated with 25 mg/12 h of captopril, for one month. If blood pressure was not under control, captopril treatment enhanced to 50 mg/12 h during second month. After this period of two months, patients under control were got out of this study. 37 patients (46.25%) needed a second drug. In randomized form, 20 patients associated 25 mg HCTZ one time a day (CAP + HCTZ); and 17 patients associated 20 mg/12 h of nifedipine retard (CAP + NIF). The study continued for 4 months more. Both treatments reduced blood pressure in significant form without changes statistical significant in the heart rate, weight, glycemia, cholesterol, triglycerides, c-HDL, uric acid, creatinine, Na+ and K+ blood levels. CAP + HCTZ controlled (DBP < 90 mHg) 85% and CAP + NIF 81.25% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439068 TI - [Determining factors of acceleration in sustained monomorphic ventricular tachycardias in response to bursts of stimuli]. AB - To analyse the determinants of acceleration of sustained monomorphic ventricular tachycardias in response to bursts of rapid ventricular pacing, we studied 46 consecutive patients with 90 distinct ventricular tachycardias during which one or more burst of rapid pacing were delivered. Tachycardia acceleration was observed in 11 tachycardias in 8 patients. The highest incidence of acceleration was observed in patients with left ventricular dysfunction of non coronary origin. There was a non significant trend towards lower values of left ventricular ejection fraction in patients with acceleration. There were no significant differences between ventricular tachycardias with of without acceleration in respect to: clinical presentation, QRS morphology, tachycardia cycle length and treatment with antiarrhythmic drugs. The shortest cycle of bursts of rapid pacing, was lower in tachycardias with acceleration than in those without it (229 +/- 57 ms vs 283 +/- 67 ms; p = 0.006) and tachycardias with acceleration showed a lower relation between burst cycle length and tachycardia cycle length (69 +/- 9% vs 84 +/- 8%; p < 0.001). The negative predictive value of acceleration was 75% for bursts of rapid pacing with a cycle length > or = 250 ms, and 96% for values of the relation between the burst cycle length and the tachycardia cycle length > or = 70%. This parameter show a very high discriminating value with of without antiarrhythmic drugs effect. Acceleration of sustained monomorphic ventricular tachycardias in response to bursts of rapid pacing depends on, the pacing rate and the relation between pacing rate and tachycardia rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439069 TI - [Transesophageal echocardiography study of the left atrium and the mitral valve plane after heart transplantation]. AB - To assess the anatomy of the left atrium and mitral plane after heart transplantation, we performed a transesophageal echocardiographic study to 37 consecutive transplant patients. After heart transplantation no patient was under anticoagulant treatment and no case of atrial fibrillation was documented. The transesophageal approach allowed us to measure the left atrial free wall suture which was: less than 15 mm in 14 patients, between 15 and 25 mm in 16 patients, and more than 25 mm in 7 patients. In those patients with a left atrial free wall suture greater than 15 mm, blood flow turbulences within the "niche" underneath the protruding suture as well as blood flow acceleration at the rim of that suture were noted. In 4 patients a "pseudoaneurysm" of the interatrial septum was observed. Two patients had mitral valve prolapse. Mitral regurgitation was noted in 17 patients (46%) by color Doppler transesophageal echocardiography and graded as mild in 15 patients and moderate in 2 cases. In 16 patients (43%) spontaneous echo contrast within the left atrium was detected by transesophageal echocardiography. Both major and minor axis as well as left atrial area in patients with and without dynamic echoes were, respectively: 72.5 +/- 12.2 mm vs 56.9 +/- 5.9 mm (p < 0.001), 48.3 +/- 7.1 mm vs 39 +/- 7.9 mm (p < 0.001), and 35.4 +/- 7.1 cm2 vs 24.4 +/- 5.2 cm2 (p < 0.001). Atrial thrombi were not detected. After a mean follow-up of 15 +/- 10.7 months there was no arterial thromboembolism in patients with spontaneous contrast.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439070 TI - [Isosorbide 5-mononitrate (delayed release) in stable effort angina]. AB - This work has been carried out to evaluate over a short and medium space of time (100 days) the efficacy, tolerance and haemodynamic repercussion of 50 mg of sustained release Isosorbide 5-Mononitrate administered once day to patients with stable effort angina in a random and prospective study, which was double blind crossover and placebo-controlled. In this study we included 10 patients who showed positive exercise test using clinical (angina) and electrocardiographic (ischemic drop of the ST greater than 1 mm) criteria. The assessment was done with cycloergometry starting with 30W and increasing by 20W every 2 minutes until angina appeared accompanied by an ischemic drop of the ST. The effort tests were done basally and at intervals of 4, 12 and 24 hours after the dose. The parameters studied were obtained on the 1st, 25th and 100th days of the study and were compared with those of the placebo. The time taken for the ST to 1 mm to fall (seconds) increased when evaluated after 4 and 12 hours on the 1st, 25th and 100th days in comparison with placebo (p < 0.05). The time taken for angina (seconds) to appear lengthened considerably when evaluated 4 and 12 hours after the dose not only on the 1st day but also on the 25th and 100th days in comparison with placebo (p < 0.05). The duration of the effort (seconds) was significantly greater after 4 and 12 hours on the 1st, 25th and 100th days when compared to that of the placebo (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439071 TI - [Effect of the inhalation ++ anesthetic isoflurane on heart electrophysiology]. AB - In two groups, A and B, both composed of 10 mongrel dogs, we studied the cardiac electrophysiologic effects of 1 and 1.5 MAC isoflurane administered by liquid injection in a closed circuit. In group B the study was done under pharmacological autonomic blockade (AB). With electrode catheters for programmed pacing and endocavitary potential recordings, we determined during the anesthesia with 1 and 1.5 MAC isoflurane: RR, spontaneous and paced AH, and HV intervals, corrected sinus recovery time (CSRT), Wenckebach point (WP), functional and effective refractory periods of atria (AFRP, AERP) and AV node (AVNFRP, AVNERP), and ventricular effective refractory period (VERP), these were compared to the ones obtained with a previous thiopental control. In group A, 1 MAC isoflurane increased over control: AERP and AH interval (p < 0.05), AFRP (p < 0.005), RR and AH paced intervals, WP, AVNFRP and VERP (p < 0.001), adding to these CSRT (p < 0.01) in 1.5 CAM. This level did not show differences with 1 MAC. In group B, 1 MAC isoflurane increased over control: AH (p < 0.05), RR, paced AH intervals, WP and AVNFRP (p < 0.001), adding to these AFRP and AERP (p < 0.05) in 1.5 MAC. This level increased with regard to 1 MAC: AFRP, AERP, AH paced interval and AVNERP (p < 0.05), and AVNFRP (p < 0.005). Isoflurane alone or with AB increased parameters of sinusal automaticity, atrial refractoriness, AV nodal conduction and refractoriness, increasing only without AB ventricular refractoriness and CSRT. With AB atrial and AV nodal refractoriness increased in an anesthetic depth dependent way. PMID- 1439072 TI - [Chronic heart insufficiency (XI). Molecular biology of heart insufficiency]. PMID- 1439073 TI - [Lipomatous hypertrophy of the interauricular septum: diagnosis with transesophageal echocardiography and computerized tomography]. AB - Transesophageal echocardiographic and computed tomographic imaging in a patient with lipomatous hypertrophy of the interatrial septum and advanced left bundle branch block are presented. Transesophageal echocardiography demonstrated a thickening of the atrial septum sparing the fossa ovalis region. Computed tomographic scan at the level of the interatrial septum showed a mass of fat density, and the HIS bundle electrogram showed an advanced infra-his block after intravenous ajmaline. We stress the utility of transesophageal echocardiography in this disorder, and the possible relationship between lipomatous hypertrophy of the interatrial septum and conduction disturbances. PMID- 1439074 TI - [Listeria monocytogenes endocarditis in a patient with mitral prosthesis, left auricular thrombus and adenocarcinoma of the colon]. AB - A case of Listeria monocytogenes endocarditis in a patient with mitral prosthetic valve, left atrial thrombus and colonic adenocarcinoma is reported. Vegetations were not demonstrated by transesophageal echocardiography and the clinical course was benign and without complications. Cure was achieved with antibiotic therapy, and surgery was not required. These features suggest that atrial thrombus could be the source of infection. PMID- 1439075 TI - [Ultrasonic decalcification of the aortic valve. Initial experience]. AB - We report our initial experience in 2 patients with degenerative calcific aortic stenosis who underwent ultrasonic debridement of the aortic valve. Compared with preoperative studies, doppler echocardiographic and hemodynamic evaluation before hospital discharge revealed a reduction in the mean aortic valve pressure gradient (80 and 65 mmHg to less than 10 mmHg). There was no change in aortic regurgitation grade. Follow-up doppler echocardiographic evaluation at four and six months showed no changes in gradient or regurgitation in the comparison to the postoperative data. Long-term results will show the convenience to attempt or not ultrasonic salvage of the native aortic valve in severe calcific stenosis. PMID- 1439076 TI - [Bullet embolism of the right ventricle following gunshot wound]. AB - Bullet embolism to the right ventricle after a gunshot wound is exceptional. We describe a patient in whom the bullet after entering through the superior vena cava migrated for the venous system with further embolism to the right ventricle. Clinical history, diagnosis and treatment are discussed. PMID- 1439077 TI - Relationship between erythropoietic rate and iron donating capacity of the Fe/transferrin complex in mouse. AB - The transfer of iron from the Fe/transferrin complex to the erythroid cells was studied in in vitro system in mice in which a drastic and opposite change in their erythropoietic activity was produced by bleeding or actinomycin D administration. A reduction of iron donation in the serum of bled animals was found, whereas the aplastic condition induce in the donors of the serum by actinomycin D did not produce any change in the transfer process. It was also found that in spite of the normalization of the saturation in the serum of bled animals, the diminished donation remained unchanged. The possibility that conditions other than quantitative could produce this behavior is discussed. PMID- 1439078 TI - Effects of methylpalmoxirate on isolated rat atria. AB - The aim of the investigation was to assess whether endogenous triacylglycerol contributes to the maintenance of the contractile and pacemaker activities of the isolated atria from fed and fasted rats. To attain this information, the atria were treated with methylpalmoxirate which is a potent inhibitor of carnitine palmitoyltransferase I. In the presence of glucose, methylpalmoxirate abolished the lipolysis without affecting peak developed tension or the atrial rate. When exposed to a substrate-free medium containing 2-deoxyglucose, the atria displayed a progressive fall of the pacemaker frequency, a pronounced decay of contractile strength and the appearance of contracture. These derangements appeared faster in the atria from fed rats coinciding with a smaller triacylglycerol mobilization. Methylpalmoxirate suppressed triacylglycerol breakdown, increased the contracture strength, accelerated the fall of the atrial rate and in a significant number of fasted atria it led to a complete cessation of the spontaneous contractions. The decline of the peak tension was not altered by the inhibitor, probably because the contractile strength was too weak in the glucose-free medium, so that additional negative inotropic effects were not detectable. These data suggest that exogenous glucose in addition to that derived from glycogen meet the atrial energy requirements when the fatty acid oxidation is hindered. The deleterious effects exerted by methylpalmoxirate after the glucose metabolism was eliminated indicate that endogenous triacylglycerol supports, at least partly, the atrial functions. PMID- 1439079 TI - [Effect of brain serotonin on the arterial pressure and plasma renin in normal and hypertensive rats]. AB - The effects of changes in brain serotonin content after injections of p chlorophenylalanine (p-CPA), L-5-hydroxytryptophan (L-5HTP) and 5-6 dihydroxytryptamine (5-6DHT) on the mean arterial pressure (MAP), plasma renin activity (PRA) and peripheral levels of atrial natriuretic peptide (ANP) have been studied in normal and hypertensive (2K:1C model) male Wistar rats. The p-CPA (250 mg/kg) and L-5HTP (200 mg/kg) were injected i.p., while 5-6 DHT (15 micrograms/animal in 10 mu/animal vehicle) was injected into lateral brain ventricles. The effects were studied 24 h after the p-CPA injection, 2 h after L 5HTP and 10 or 20 days after 5-6DHT administration. The fall in brain serotonin produced by p-CPA and 5-6DHT did not modify the MAP values in the normal and hypertensive rat model, whereas the increase induced after L-5HTP injection only caused a slight decrease in arterial pressure in normotensive animals. The ARP experimented remarkable rises in the normal and hypertensive rats, these values increasing after L-5HTP and falling after p-CPA and 5-6 DHT injections. Similar changes are detected in the normal group after administration of these substances related to serotoninergic brain activity. The ANP levels rose after renal artery constriction, and they are not affected by the above mentioned substances. Only p CPA and 5-6DHT reduced a low decrease in the ANP levels 10 days after their administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439080 TI - Muscle cell growth in protein deficient rats following administration of sheep red blood cells. AB - In order to observe the effects of sheep red blood cells (SRBC) administration on the muscle cell growth in malnourished states, adult male Wistar rats (135 +/- 10 g 10 animals per group) subjected during 30 days to 1% and 10% protein diets, were injected (i.v.) either 15.5 x 10(8) sheep red blood cells or 0.5 ml saline/100 g b.w. after 20 days of experiment. On the 10th day after injection the animals were sacrificed and the gastrocnemius muscle was removed, weighed and homogenized. The supernatant fluids were used to evaluate muscle protein, DNA and RNA rates and acid DNase activity. All parameters were depleted in malnourished rats, indicating a muscle cellular atrophy as well as a decrease in muscle protein synthesis per DNA-unit. Muscle hyperplasia and hypertrophy were found in antigenically stimulated rats fed 10% protein against non-stimulated control. In contrast, muscle growth in protein-deficient rats SRBC-treated was unmodified when compared to non-stimulated malnourished muscle, although RNA functionality seems to be enhanced (RNA/DNA). These data suggest that a redistribution of essential nutrients occurred for muscle growth adaptation rather than for defensive mechanism. PMID- 1439081 TI - Role of -SH groups in rat sugar intestinal transport in vivo. AB - The effect of p-chloromercuribenzoic acid (pCMB), either alone or in the presence of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), on the 1 mM galactose absorption by in vivo perfused rat intestine has been studied. At 0.25 mM concentration, pCMB inhibits galactose absorption in about 32% but it does not modify the absorption of this sugar when the transport is blocked by 0.5 mM phlorizin, or that of the non-transportable monosaccharide derivative 2-deoxy-D-glucose. This shows that only the active transport component of galactose absorption is inhibited. A 2 min preexposure period is required for the inhibition to appear. The inhibition was not reversed by washing with saline solution even when it contained 0.5 mM dithioerythritol, 10 mM cysteine or 5 and 10 mM EDTA. The simultaneous exposure to 0.25 pCMB and 0.25 mM DTNB inhibits the total galactose entry in about 50%, an effect higher than the one exerted by each reagent separately and close to the one obtained with 0.5 mM phlorizin. Our results, in vivo, confirm the importance of the thiol groups in the cotransport of Na+ and sugar. As DTNB is an SH-reagent of lesser liposolubility than pCMB, the existence of two populations of sulfhydryl groups related to sugar transport which differ in their location within the brushborder membrane and in accessibility from the intestinal lumen, is suggested. PMID- 1439082 TI - Chloroplast polypeptides synthesized by leaf segments and isolated chloroplasts during senescence in barley. AB - Starting from senescent barley (Hordeum vulgare L. cv Hassan) leaf segments receiving light and hormone treatments affecting senescence, the plastid polypeptides synthesized by isolated chloroplasts and by leaf segments were analyzed by radiolabelling followed SDS-PAGE and fluorography. Among 20 to 30 polypeptides detected, a few were specifically synthesized (by chloroplasts and/or leaf segments) after each senescence treatment. Apparently, the polypeptides labelled in assays with isolated chloroplasts are truly synthesized in vivo, because most of them were also labelled in assays with leaf segments. The comparison of polypeptide profiles, for every senescence treatment, after labelling with isolated chloroplasts or leaf segments, suggests that most plastid polypeptides synthesized during senescence are coded in plastid DNA. PMID- 1439083 TI - [Effect of the corpora allata on the development of the male accessory sex glands in Blatta orientalis]. AB - The volumetric changes of the corpora allata (CA) during the first 15 days of imaginal life of Blatta orientalis L. (Dictyoptera, Blattidae) are studied in connection with the growth of the accessory reproductive glands (GSAM). Both, the CA and the GSAM, grow in parallel during the first 3-4 days of imaginal life, which suggests a possible functional link between both organs. If the CA are explained on freshly ecdysed adults, then GSAM protein accumulation is reduced (by 35%) when checked on day 5, and administration of juvenile hormone (JH) restores normal development. However, when the effects of allatectomy are studied on day 12, no significant differences with respect to the controls are observed. These results suggest that JH is not strictly necessary for protein synthesis in the GSAM of B. orientalis although it has a stimulatory effect on this synthesis. PMID- 1439084 TI - [Comparison of homologous and heterologous standard curves using TR-FIA for the determination of total T4 in the rat]. AB - A homologous standard curve for rat T4 measurement has been compared to heterologous standard curves, by a time resolved fluoroimmunoassay (TR-FIA). Homologous standard curves have been carried out starting from rat serum in the absence of thyroid hormone by using Samuel's technique. The security criteria (sensitivity, inter and intraassay precision, and accuracy), were measured and compared between the homologous and heterologous test. Analysis of variance and slopes between homologous and heterologous standard curves showed homogeneous variances, the differences in the slopes being not significant. PMID- 1439085 TI - Acute alcoholic intoxication and naloxone. Effects on visual evoked potential. AB - Experimental assays analyzing visual evoked potential (VEP) changes during an acute alcoholic intoxication were carried out in two groups of cats: One with continuous ethanol (0.06 g/kg.min) i.v. perfusion. Another one with a naloxone (400 micrograms/kg) i.v. injection 10 min before ethylic perfusion. Naloxone potentiates alcohol effects on VEP parameters, and on the appearance of isoelectric postpotential and flat VEP. PMID- 1439086 TI - Normal puberty onset in female rats treated with antiprogesterone RU486 during juvenile period. AB - The significance of the increased progesterone plasma levels after day 21 on the onset of puberty in female rats is unclear. To analyze this question, female rats were injected from day 21 to 32 with the potent antiprogestagen RU486 (1 mg/day) or vehicle. Treatment with RU486 did not modify either the age at which vaginal opening or first estrus occurs. Vaginal cycles were regular. Animals sacrificed on day 40 or 50 showed reduced uterus weight, whereas body, pituitary, adrenal and ovaries were not affected. These results evidence that antagonization of progesterone action during the juvenile phase did not affect the onset of puberty. PMID- 1439087 TI - Glucose tolerance tests during gestation in the unanesthetized rat. AB - To establish the temporal stages at which changes in insulin/glucose interactions may appear during gestation in the rat, unanesthetized animals were subjected to oral glucose tolerance tests (2 g glucose/kg) at days 15 and 21 of gestation and were compared to virgin female controls. On day 15 glucose tolerance is enhanced in the pregnant rat whereas plasma insulin levels are like those in control animals. On day 21 glucose tolerance does not differ between the two groups although insulin is higher in the pregnant animals. Results show 2 differentiated stages of insulin/glucose relationships throughout gestation in the rat with enhanced insulin sensitivity on day 15 and enhanced insulin resistance during late gestation. It is suggested that these changes contribute to the anabolic tendencies of the mother during mid gestation and her catabolic condition during late gestation. PMID- 1439088 TI - [Loop diuretics and the treatment of asthma]. AB - Current data in the literature show a protective effect of loop diuretics in relation to certain types of experimental bronchospasm. This action has sometimes been observed after the administration of diuretics as aerosols in less severe cases of asthma. The initial observations on bronchospasm induced by physical stimuli (exercise, distilled water and hyperventilation), have been extended to bronchospasm provoked by allergens or certain chemical stimuli (metabisulphide, adenosine 5'-monophosphate, and salicylic acid). On the other hand provocation tests using histamine or acetylcholine are modified, either a little or not at all by diuretics. The proposed mechanisms of action are multiple, but are still very hypothetical: an action on ionic fluxes in the epithelial cells, in mastocytes, in nerve cells and in muscle cells inducing the secretion of prostaglandin. Diuretics certainly have opened some interesting patho physiological approaches, but current data concerning their efficacy in asthmatics are still fragmentary and do not, at the current time, allow them to take a significant place in the therapeutic arsenal of asthma drugs. PMID- 1439089 TI - [Mortality related to asthma. Trends in France from 1970 to 1987]. AB - An increase in mortality related to asthma has been observed in a great number of countries during the last decade. The purpose of this work is to study this evolution in France from 1970 to 1987. Numbers of deaths were obtained from INSERM, by sex and age groups and the corresponding populations from INSEE. Data were interpreted from crude rates and with the computation of age adjusted and age specific rates. In men, we observed a decrease in mortality from 1972 to 1979, then an increase from 1980 to 1987. In women, the decrease stopped as early as 1974 and we observed an increase from 1975 to 1987. On the other hand their crude and age-adjusted rates become higher than men's rates as early as 1977. PMID- 1439090 TI - [The influence of a new beta agonist: formoterol on mucociliary function]. AB - The muco-ciliary apparatus has an essential role in the cleansing of the tracheo bronchial tree of particulate matter. Disturbances linked to muco-ciliary function are well known in respiratory pathology and in cases of chronic bronchitis and asthma and lead to a reduced capacity for cleansing. In addition there are numerous pharmacological agents including sympathomimetics which are capable of altering the ciliary activity and the rheological properties of mucous. The role of Formoterol, administered as an aerosol has been assessed in vivo in 10 bronchitic patients who were in a stable state. After 6 days of treatment using the Formoterol aerosol the muco-ciliary clearance had significantly increased to 46% and was a real gain when compared to the muco ciliary clearance measured on placebo. This gain was linked to a better function of the muco-ciliary carpet and not due to the bronchodilatation which was induced by Formoterol, because the penetration index did not change. At the same time the airway resistance was slightly reduced in a none significant fashion. PMID- 1439091 TI - [Bronchogenic cysts in the carina]. AB - Between 1977 and 1990, 11 children with carinal bronchogenic cysts were operated in our institution: 8 girls and 3 boys, ranging in age from 1 month to 5 years. All were symptomatic (acute respiratory distress and recurrent bronchiolitis). Chest X-ray showed an unilateral over distension in 10/11 cases. Barium oesophagogram showed a compression in 6/10 cases. Bronchoscopy noticed an extrinsic compression in 10/11 cases and a tracheal and/or bronchial diskinesia in 5/11 cases. The computed tomography showed a low density mass in 4/4 cases. 9 cysts were left-sided and 2 right-sided. Both children underwent a second surgery for a second cyst. 2 pneumonectomies for complete parenchyma destruction were realised. 1 left pulmonary hypoplasia was noticed. A tracheal and/or bronchial diskinesia in post-operative was noticed in 5/6 cases. The clinical and functional respiratory following was good in 10/11 cases. An early surgery treatment is necessary before definitive sequelae. PMID- 1439092 TI - [Evolution of bronchial hyperreactivity during post-exercise asthma]. AB - The occurrence of a late reaction following exercise induced asthma is questionable and its relationship with the non specific bronchial hyperreactivity is poorly known. In this study, nine patients (age 15-21 years) underwent an exercise challenge in order to (a) determine the incidence of immediate and late phase reaction and (b) analyse the modifications of non specific bronchial hyperreactivity. Study design was a follow; day-3: determination of bronchial responsiveness to metacholine; day 0: control day with FEV1 measurements every hour for 11 hours; day 1: exercise challenge followed by a careful observation of change in FEV1; day 2: new determination of bronchial responsiveness to metacholine. An immediate exercise induced bronchial obstruction was observed in 5 patients. A late phase reaction (6th hour) with a fall of FEV1 equal to or more than 20% has been demonstrated in two patients. For the former, the change in FEV1 did not differ from the value of the control day. For the second, the FEV1 changed spontaneously during the control day so that decreases of FEV1 during control and challenge days were parallel. Thus, no late phase reaction were observed (F = 0.46; ns). There was no modification of bronchial responsiveness to metacholine (pre-exercise: 1,784 +/- 1,970 [SD]; post-exercise 1,827 +/- 2,231 micrograms [SD]). The lack of true late phase reaction when the post-exercise change in FEV1 is compared to the one of a control day and the absence of modification of non specific bronchial hyperreactivity weaken the hypothesis of an inflammatory mechanism of exercise induced asthma. PMID- 1439093 TI - [Bronchial cancers invading the chest wall]. AB - One hundred and twenty five patients, considered as having a bronchial carcinoma invading the chest wall, suffered from a thoracic pain in 40 cases. They were operated on by pneumonectomy (23), bilobectomy (5), lobectomy (83) and atypical resection (1). Resection was impossible in 13 cases (10.4%), for anatomical (10) or functional reasons (3). Considering the chest wall, an extra-pleural resection was performed in 49 cases, a muscular resection in 25 cases and a skeletal resection in 38 cases. Parietal invasion was microscopically confirmed for 78 tumours out of 112 resections specimens and for 10 tumours out of 13 which were not resected: 65 T3 N0, 8 T3 N1, 15 T3 N2. Operative mortality was 12.5%. Global survival was 62.8% at 1 year, 14.2% at 3 years, 11.1% at 5 years. Median survivals were 393 days after resections dating back to more than 5 years and 158 days when the tumours were not resected. Thoracic pain is a symptom of chest wall invasion in 87.5% of cases, but the invasion is symptomless in 24% of cases. Sensitiveness, specificity and predicting values of imaging modalities are discussed: on the whole the negative predictive values are feeble (0.23 to 0.42). The operative estimation is also uncertain, especially considering invasion limited to the extra-pleural space. Practically, a fixed tumour with broad and firm adhesion to the chest wall is an indication for chest wall resection which gives better results, although this advantage is not statistically significant. Surgical prognosis of T3 cancers is, in this series, much worse than the prognosis of T2 tumours. Mortality is analyzed according to its causes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439094 TI - [High school students and tobacco. A survey of 630 students in Poitiers]. AB - A survey of high school pupils and their attitudes to tobacco was carried out by an anonymous auto questionnaire by 630 pupils at the Alienor Aquitaine Lycee in Poitiers in April 1991. The population study had the following characteristics: 30% were boys, 70% were girls. The mean age was 18 +/- 1.31 years. The proportion of regular smokers (at least one cigarette per day, every day) was 33.9% in boys and 34.9% in girls. The boys had smoked on average 10.7 cigarettes per day for 3.5 years and the girls 9.1 cigarettes per day for 2.9 years. The smoker above all, used light colour tobacco (with filters 98%) but 29% only bought mild cigarettes. On the other hand 55% of the subjects wished to stop smoking. There was no statistically significant relationship between the smoking habits of the pupils and that of their parents on the one hand or on the regular participation in a sport, on the other. However, boarders smoked a lot more than the other pupils. The knowledge of the dangers of smoking were imperfectly understood, in particular, for chronic bronchitis, myocardial infarction, small birth weight of the newborn and cancer of the bladder. The changers of passive smoking were known by 91.6% of the pupils. Finally this study explored the opinion of the lycee pupils as regards to the six measures in the propaganda against smoking and on seven methods of information relating to the dangers of tobacco. PMID- 1439095 TI - [Expiratory capnography in asthma. Perspectives in the use and monitoring in children]. AB - The shape of the capnogram, which is related to uneven ventilation, is modified in obstructive diseases and especially during crisis of asthma. The most significant change is a rise in the slope of the "alveolar plateau". In this study, we measured the end-tidal slope (ETS) of the capnogram, calculated on 0.36 s before the end of expiration, and we compared this indice to usual spirometric measurements (FEV 1) in 21 control subjects and in 24 asthmatic subjects. The mean ETS in control subject was 0.08 +/- 0.06%/s, it was 0.3 +/- 0.23% in asthmatic subjects (p < 0.001). In the latter, we found a very significant correlation between ETS and FEV 1 (r = 0.83, p < 0.001). Thirteen asthmatic subjects were tested for a second time, immediately after inhalation of a beta 2 mimetic drug. They exhibit a very strong correlation between the rise of FEV 1 and the loss of ETS (r = 0.96, p < 0.001). These results show that the analysis of the capnogram's shape is a quantitative method for evaluating the severity of the bronchospasm. This ability, added to specific advantages (non-invasiveness, effort-independence) opens new fields of application to capnography: measurement of the bronchospasm in children, computerized monitoring of asthma. PMID- 1439096 TI - [Idiopathic subacute pulmonary eosinophilia]. AB - We report a case of pneumonia with hypoxaemia and a swinging fever which was resistant to antibiotics, but was associated with a hypereosinophilia (44%) noted in the bronchoalveolar lavage. Investigations as to the cause of the eosinophilic pneumonia were negative; a lung biopsy confirmed the eosinophilic infiltration and the absence of any angiitis. There was a rapid and favourable clinical outcome following steroid therapy, which was maintained for three months. No relapse has been noted in the ten months of follow up since ceasing the cortico steroids. The diagnosis appears to be that of a sub-acute, idiopathic eosinophilic pneumonia. The similarities and differences between this case and the chronic idiopathic eosinophilic pneumonia of Carrington were discussed. PMID- 1439097 TI - [A rare and curable cause of acute respiratory insufficiency after a pneumonectomy. The platypnea-orthodeoxia syndrome by the reopening of the foramen ovale]. AB - We describe a case of a 54 year old patient who had developed a right to left shunt due to a patent foramen ovale as a late consequence of a pneumonectomy; this was responsible for acute respiratory insufficiency and respiratory failure. This is a rare complication, but its clinical presentation as platypnea orthodeoxia should lead to the correct diagnosis. The diagnosis can be rapidly confirmed by a non-invasive examination, namely contrast echocardiography, coupled with color doppler. The treatment is surgical with excellent results. The pathophysiological mechanism is also discussed. PMID- 1439098 TI - [Generalized histoplasmosis due to Histoplasma duboisii with mediastino-pulmonary infection. Cure after 15 months of treatment with ketoconazole]. AB - We report a case of a young burkinabian, who presented with the disseminated african form of histoplasmosis, Histoplasma duboisii. There was pulmonary mediastinal disease with superficial lymphadenopathy and also hepatic involvement. The diagnosis was achieved by a histological examination of the peripheral glands and micrological examination of the expectorate. A clinical cure (despite the radiological persistence of enlarged but stable left hilar glands) with the follow up 10 months was achieved after 15 months of treatment with ketoconazole in a dose which was increased to 10 mg/kg/day. PMID- 1439099 TI - [A unilateral hyperlucent lung...]. AB - The occurrence in a young patient of a chronic cough with dyspnoea and restrictive ventilatory failure as shown by respiratory function tests suggested the possibility of a Mac Leod syndrome. However, other aetiologies could be considered such as vascular malformations, bronchial malformations and also tumours. If the chest X-ray sometimes enables an aetiological slant, bronchoscopy remains a first line investigation. PMID- 1439100 TI - [Late diagnosis of mucoviscidosis based on the association of bronchiectasis and sterility]. AB - We report a case of a man aged 36, in whom a diagnosis of mucoviscidosis was diagnosed based on the association of diffuse bronchiectasis and obstructive azoospermia. We discussed some clinical and biological aspects leading to the diagnosis of mucoviscidosis in the adult. PMID- 1439101 TI - [Purulent pleurisy revealing an esophageal diverticulum]. AB - We report a very rare case of a purulent pleurisy which was revealed to be caused by an oesophageal diverticulum. The pleuro-pulmonary infection probably followed the inhalation of septic material which refluxed from an oesophageal diverticulum into the trachea. This was suggested by a barium swallow which showed the transit of the barium into the trachea during swallowing movements. PMID- 1439102 TI - [Pneumology in the French language. Actions for countries having a common usage of French]. PMID- 1439103 TI - [Maximum pressures in the mouth: how variable are the measurements?]. PMID- 1439104 TI - [Wilson's disease]. AB - Wilson's disease, also called hepatolenticular degeneration, is a serious inherited disorder of copper metabolism. The disease needs a particular attention because it is estimated that about half of the patients are never diagnosed. Beside, once the diagnosis is made, Wilson's disease can be effectively treated. After the epidemiological, pathogenetical and clinical data, authors present the diagnostical aspects of the disease, and the various approaches to the treatment of the symptomatic or presymptomatic patients and of the pregnant patients. Also reported are two cases of Wilson's disease. PMID- 1439106 TI - [A 24-hour blood pressure and heart rate pattern in healthy persons over 70 years of age. A Campodimele study]. AB - The present report is aimed at studying the 24-h pattern of blood pressure in elderly subjects (45 men and 47 women, aged from 76 to 102 years), recruited in Campodimele, a small city where the population of ultra septuagenaries is very dense. The investigation has been performed by mean of ambulatory non-invasive monitoring combined with chronobiometric estimates. The computation has been performed on raw data, rhythmic series and integral profiles. The analysis has been stratified according to sex. The tabulated estimates constitute an index of reference for blood pressure 24-h pattern in aged people. PMID- 1439105 TI - [Insulin-like growth factors in human pathology]. AB - IGFs-I and -II are single chain polypeptides (70 ad 67 aa respectively) structurally similar to proinsulin, synthesized ubiquitously and circulating carried by specific binding proteins. The IGFs act through two types of specific membrane receptors: the so called "type 1" or IGF-I receptor, and the "type 2" or IGF-II receptor. In physiological conditions IGF-I is correlated with GH secretion. However it is also influenced by other hormonal and non-hormonal factors. Little is known about the physiological significance of IGF-II, whose concentration, at variance with IGF-I, is not increased in acromegalic subjects. It has been recently postulated that IGF-II has a critical role in prenatal growth, while IGF-I exerts its action after birth. IGF-I is important in the clinical evaluation of growth defects and of acromegalic patients. As to growth defects an overlapping of values is reported between normal and hypopituitary subjects under 5-6 years of life. However, although it is possible that a normal subject presents with a reduced IGF-I concentration, it never happens to find a hypopituitary subject with normal values. It is, therefore, possible to establish a cut-off value (100 micrograms/l in our experience) over which the occurrence of hypopituitarism is excluded. On the contrary IGF-I concentration is extremely useful in the evaluation of acromegaly, in particular to evidence the disease activity status. Moreover the IGF-I concentration seems to be useful to evaluate the nutritional status, particularly in association with serum transferrin, in subclinical conditions and in the monitoring of the nutritional therapy. PMID- 1439107 TI - [Prosopagnosia. Description and discussion of a clinical case]. AB - Prosopagnosia was due to a right occipito-temporal infarct, but clinical and computed tomographic features emphasized a previous symmetrical damage in the left side. The case reported, and especially elaboration of literature data relative to this peculiar type of visual agnosia, suggest that bilaterality of cerebral lesions in the determining factor of prosopagnosia. PMID- 1439108 TI - [Pheochromocytoma and homolateral stenosis of the renal artery. A rare association?]. AB - A case of association between pheochromocytoma and homolateral stenosis of renal artery is discussed. Until now, this is the first notification of such an association. The authors examine the possibility of a link between the two pathologies on the basis of congenital or physical factors. This association could have been so rarely just only due to the difficulty to prove it. PMID- 1439109 TI - [Diagnosis of cardiocirculatory autonomic failure by the tilting method]. AB - The variation of SBP, DBP and HR is evaluated on tilting in a group of 34 patients affected by orthostatic hypotension versus a group of 54 healthy subjects, age and sex cross-matched. The patients affected by cardiovascular autonomic failure showed: 1) a fall of SBP greater than -19 mmHg in the 1st min; 2) a fall of the SBP average value (for 10 minutes) greater than -22 mmHg. Contrarily, the healthy subjects showed: 1) no variations of SBP values during the 1st minute and 2) a growing of SBP between the 2nd and the 10th minute; 3) a SBP average value (for 10 minutes) with a positive trend. The DBP and HR showed not differences between the groups. We suggest that the measure of SBP on standing may be considered an easy and fast method to perform a diagnosis of autonomic cardiovascular failure. PMID- 1439110 TI - False positivity of tumor markers in pleural fluid of traumatic hemothorax. AB - Various biochemical parameters of pleural fluid have been employed to identify malignant effusions. However, many of them are also elevated in patients with nonmalignant conditions. We report on a patient with traumatic hemothorax, showing high pleural fluid concentrations of ferritin, tissue polypeptide antigen, and cancer antigen 125. This patient's pleural fluid also contained high levels of bilirubin and many macrophages containing phagocytized red blood cells, suggesting a local metabolism of hemoglobin. Our case confirms that some tumoral markers can give false positive results and suggests that their significance must be evaluated differently in bloody pleural effusions as compared with non-bloody pleural effusions. PMID- 1439112 TI - [Controlled trial of thymostimulin treatment of patients with primary carcinoma of the larynx resected surgically. Immunological and clinical evaluation and therapeutic prospects]. AB - The study aim was that of evaluate the effect of thymostimulin (Tp-1, Serono), either in vitro or in vivo, in patients with primary laryngeal carcinoma, treated only with surgery without any other complementary therapy. Nineteen patients have been studied: nine (mean age 62.5 years, range 48-70) have been treated with Tp-1 and ten patients (mean age 63.4 years, range 56-75) served as "controls". Tp-1 has been administered as follows: 60 mg/m2/daily i.m. days 1-15; 60 mg/m2 twice weekly i.m. days 16-30; 60 mg/m2 once weekly i.m. days 31-60. The treatment was stopped days 61-90. The same cycle was repeated until day 180. The treatment was stopped days 181-365. The following parameters have been assessed: clinical (at the protocol entry and after one year): Performance Status (PF, Karnofsky), local status, presence of relapses, incidence of chronic infections of the upper respiratory tract; immunological in vitro: 1) response to polyclonal mitogens, PHA, Con A and PWM, response to human recombinant Interleukin 2 (rIL 2) of PHA prestimulated and non prestimulated peripheral blood lymphocytes. The immunological parameters also have been assessed at the protocol entry and after one year. Our results have shown that, in the group of patients treated with Tp 1, 5/9 patients (55.56%) exhibited a significant increase of the PHA response at the end of treatment as compared to pretreatment values, 3/9 (33.34%) showed a decrease and 1/9 (11.10%) an almost unchanged response. In the group of controls, 5/10 (50%) have shown a significant decrease of the response after one year, 3/10 (30%) an increase, 1/10 (10%) were unchanged and 1/10 (10%) exhibited a non univocal response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439111 TI - [Factors influencing the effect of ursodeoxycholic acid therapy in chronic hypertransaminasemia]. AB - The aim of this work was to detect, in patients with chronic hypertransaminasemia (CH), the factors associated with the changes of ALT serum levels after one year of 10 mg/Kg/die ursodeoxycholic acid (UDCA). One hundred and twenty two consecutive patients with ALT values more than twice the normal upper limit for at least six months were admitted to the study. At the liver biopsy 82 patients were affected by liver cirrhosis (LC), 7 by chronic persistent hepatitis (CPH), and 14 by chronic active hepatitis (CAH). Nineteen patients were classified as unspecified chronic liver disease (UCLD) due to biopsy refusal. Five patients (4 LC and 1 UCLD) did not finish the study. Before and after the beginning of the treatment ALT and the other routine tests of liver function were determined in serum by routine laboratory methods. In all the diagnosis a decrease of ALT was observed after one year UDCA therapy. Particularly, in cirrhotic patients a reduction of 40% in the ALT serum levels was detected (baseline m +/- ds 98 +/- 55 UI, one year transaminase decrease -39 UI with 95% C.I. -27 UI to -52 UI). Furthermore in liver cirrhosis there was an increase of serum albumin (baseline m +/- ds 3.5 +/- 0.6, one year albumin increase +0.2 gr with 95% I.C. +0.1 gr to +0.3 gr). The decrease of ALT showed an inverse association (p < 0.05) with the presence of antibodies to hepatitis C virus and with diagnosis of CAH, and a direct one with the basal values of ALT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439113 TI - [Chronic reduction of the capillary circle and neoplastic promotion]. PMID- 1439114 TI - [Prevalence and risk factors of carotid and femoral atherosclerosis in a sample of the city of Turin]. AB - Presence and severity of carotid and femoral atherosclerosis, in relation to the principal cardiovascular risk factors, have been non invasively evaluated using echodoppler in a sample of 457 subjects (average age 55.4 +/- 18.7 years) of the metropolitan area of Turin. Data of prevalence have been standardized for age and gender in order to obtain an estimate of prevalence representative of the city. In both districts, prevalence of lesions, echo structural characteristics of the plaques and related degree of stenosis have been considered. Results indicate a high prevalence of carotid and femoral atherosclerosis (38.5% and 39.4% respectively), and, particularly, of concomitant involvement of both districts (30%). Prevalence of the lesions and degree of stenosis rise with advancing age; nevertheless stenosis > 75% were not found among the oldest patients. Bifurcations were the most frequent site of lesion and the "hard" echo structure was the most commonly represented, especially in subjects over 45 years. After multiple logistic regression model both carotid and femoral atherosclerosis were strongly and independently associated with age, male sex, smoke of cigarette and plasma cholesterol concentration. PMID- 1439115 TI - [Chronic alcoholism and arterial hypertension. Contribution to the comprehension of the phenomenon and practical implications]. AB - Alcohol abuse is a frequent contributor to elevated blood pressure. 710 chronic alcoholics, aged 26-60 years, admitted for detoxification were studied. We compared hypertension prevalence in alcoholics with that in a similar group of non-alcoholics matched for age, sex, and miscellaneous diseases. The prevalence of hypertension was higher in heavy drinkers (11.4%) than in non drinker subjects (3.4%). Abstinence from alcohol during hospitalization was followed by normalization of hypertensive status in a high percentage of patients (70%). The majority of hypertensive alcoholics (75%) developed target organ damage ranging from retinopathy to hypertensive cardiomyopathy and renal lesion. In a 4.6 +/- 2.8 years follow-up study of 42 hypertensive alcoholic subjects, we observed that hypertension was 26% in those who abstained alcohol ingestion versus 84% in those who remained actively alcoholics. Four patients died of liver failure and two of stroke. PMID- 1439116 TI - Inappropriate antidiuretic hormone secretion in a patient with systemic sarcoidosis. AB - A 59 year old man presenting fever, serum hyponatremia and hypoosmolality in association with hyperosmotic urine was hospitalized in our unit in February 1988. We demonstrated evidence of systemic sarcoidosis and inappropriate secretion of antidiuretic hormone (ADH). The patient was treated with corticosteroid therapy for a period of about 1 year, with regression of signs of the inappropriate vasopressin secretion as well as the symptomatology related to systemic sarcoidosis. This study identified systemic sarcoidosis as a definite cause of "syndrome of inappropriate ADH secretion". PMID- 1439117 TI - [Clinical methodology employed to solve a case of probable sarcoidosis]. AB - A case of interstitial lung disease with fever and arthralgia is described. Sarcoidosis was very probable, but the patient refused the invasive investigations that were needed in order to obtain a histological diagnosis of certainty. We discuss the clinical methodology employed to solve the case. PMID- 1439118 TI - [Sarcoid arthritis: diagnosis by biopsy of a scar]. PMID- 1439119 TI - [Sublingual captopril in hypertensive crises]. AB - Captopril is widely used in severe hypertension. Oral administration takes one two hours to achieve a maximum effect and is not useful in hypertensive crisis. Few reports describe a more rapid effect on blood pressure following sublingual administration. We evaluated the effect of sublingual captopril 50 mg, in 26 patients with hypertensive crisis. Blood pressure levels started to decrease within 10 minutes and the maximum effect was observed 30 minutes after administration of the tablet. In all patients mean (CI 95%) systolic blood pressure dropped from 202.5 (199-206) mmHg to 160.6 (156-165) mmHg and diastolic blood pressure from 105.6 (102-109) mmHg to 86.9 (83-7-90.1) mmHg. This effect was maintained over two hours. There were no side effects. Sublingual captopril is highly effective in hypertensive crisis and its gradual hypotensive action avoid dangerous abrupt fall in blood pressure. PMID- 1439120 TI - [Evaluation of the thyroid function in healthy aged patients residing in 2 geriatric institutions]. AB - Thyroid function assessment in elderly inpatients. It is not well known whether normal ageing might lead to an impairment of thyroid function. We evaluated 297 elderly inmates in two geriatric institutions. After having excluded from the study those who were affected by chronic hepatic or renal disease, were under pharmacologic treatment or had suffered from acute ailments during the previous two months, we assessed thyroid function by determining circulating T4, T3, rT3, FT4, FT3 and TSH in 130 apparently healthy subjects. They could be divided into three groups composed of patients mentally competent, affected by either vascular or senile dementia, or affected by chronic psychosis. Results were also assessed with reference to three different age ranges (65-74, 75-84 and over 85 years). Two patients had subnormal thyroid hormone levels with elevated basal thyrotropin, while other two demonstrated only elevated thyrotropin levels, qualifying respectively for a diagnosis of primary hypothyroidism and subclinical hypothyroidism. In the remaining 126 patients thyroid function was normal, and no differences in thyroid hormone levels could be noticed among the various groups of patients, divided for sex, age range and mental condition. The results of our study confirm the presence of a high percentage of subclinical thyroid dysfunction in old age. They also suggest that in healthy aged subjects thyroid function parameters are not significantly different in reference to sex, age range and mental condition. PMID- 1439121 TI - [Hypertension: when to consider it a risk factor?]. AB - The results of a good deal of large epidemiological studies carried out in the last 3 decades clearly showed that moderate and severe arterial hypertension is a mayor risk factor for cardiovascular disease. At variance, mild hypertension was generally regarded as a more benign condition, if not associated with other risk factors. Recently, the attention of several investigators was focussed to identifying possible additional risk factors, which are related to high blood pressure, and might increase substantially the risk of mild blood pressure elevation. Left ventricular hypertrophy, activation of the renin-angiotensin system and a generalized increase in the Na+/Li+ countertransport are some of the factors that are implicated in hypertensive cardiovascular disease. Since not all available antihypertensive agents positively influence these factors, these observations could have not only pathophysiological and clinical, but also therapeutic consequences. PMID- 1439122 TI - [Recent biological and therapeutic advances in multiple myeloma]. AB - Multiple myeloma still remains a fatal disease. However, in the last months new biological and clinical informations have been provided about this disease. In particular, the immunophenotype of myeloma cells seems indicate, in some patients, a clonal involvement of a stem cell in the pathogenesis of mieloma. Moreover, new biological insights concerning the cytokine network, have revealed a probable effect of some cytokines, such as IL6, IL3, IL4. Finally, new insights in the biology of multiple myeloma have been provided by studies of molecular biology and flow cytometry. As for therapy, the best conventional induction treatment still remains to be defined. In the last years, the increased use of alpha Interferon and new therapeutic modalities, such as transplantation procedures in multiple myeloma, open new hopes toward a cure of this disease. Therefore, in the future a better knowledge of the multiple myeloma biology, associated with a wider use of new effective therapeutic approaches will certainly improve the natural course of this disease. PMID- 1439123 TI - Immunotherapeutic approaches with monoclonal antibodies to immunological diseases. AB - The molecular events triggered by the interaction of the immune system with an antigen and leading to an immune response have been characterized in recent years. This information has provided the background to develop immunotherapeutic approaches to allograft rejection and to autoimmune diseases utilizing monoclonal antibodies to molecules which play a role in the immune response. The clinical trials performed thus far are described. The significance of the results obtained in these trials and the future potential developments are discussed. PMID- 1439124 TI - Characteristics and practical use of new-generation adjuvants as an acceptable alternative to Freund's complete adjuvant. PMID- 1439125 TI - Characteristics and practical use of new-generation adjuvants as an acceptable alternative to Freund's complete adjuvant. PMID- 1439126 TI - Freund's complete adjuvant: an effective but disagreeable formula. PMID- 1439127 TI - Bacterial cell wall products as adjuvants: early interferon gamma as a marker for adjuvants that enhance protective immunity. PMID- 1439128 TI - Aluminum salts. PMID- 1439129 TI - DDA as an immunological adjuvant. AB - As compared to other adjuvants, DDA is a moderate or strong adjuvant for humoral responses and a strong adjuvant for CMI, especially DTH responses, against different types of antigens and in both laboratory animals and larger animals. DDA can collaborate with other immunomodulating compounds resulting in further enhanced responses. Mechanisms include interactions with both antigen and components of the host immune system and possibly, multiple beneficial effects contribute to the relatively strong adjuvanticity of DDA. Toxicity of DDA is not known but severe detrimental side effects were not seen. This adjuvant can be applied in experimental vaccines and in commercial vaccines for veterinary purposes, especially if cell-mediated immunity is considered to be important. In immunology, DDA can be of use to study T helper cells responsible for DTH responses (T helper cells type 1) and to characterize T helper cell epitopes on antigens (Snijder et al., 1992). PMID- 1439130 TI - Adjuvant properties of stable water-in-oil emulsions: evaluation of the experience with Specol. PMID- 1439131 TI - Non-ionic block polymer surfactants as immunological adjuvants. PMID- 1439132 TI - Syntex adjuvant formulation. PMID- 1439133 TI - Saponin. PMID- 1439134 TI - The iscom structure as an immune-enhancing moiety: experience with viral systems. PMID- 1439135 TI - Liposomes as antigen carriers and adjuvants in vivo. PMID- 1439136 TI - Synthetic lipopeptides as novel adjuvants. AB - Lipopeptides constitute potent novel immunoadjuvants in mice, rabbits and other species, enhancing markedly the immune response when given in mixture with antigens. Lipopeptides are non-toxic, non-pyrogenic and do not induce tissue damage when injected. They are thus well suited to replace Freund's adjuvant avoiding its side effects; the antibody titres obtained using lipopeptide analogues are in most cases comparable to the titres obtained by administering Freund's adjuvant. Lipopeptides also improve the efficiency of vaccines, which is important in decreasing the amount of vaccine required. Lipopeptides covalently coupled to low molecular weight haptens, e.g. peptides or toxins, are able to elicit high antigen-specific antibody titres in mice and rabbits. Conjugates containing B or T helper cell epitopes constitute novel synthetic vaccines which protect against viral infections by inducing virus-specific antibodies. When coupled to CTL epitopes, the conjugates are able to induce cytotoxic T lymphocytes in vivo which eliminate virus-infected cells. Thus, due to their efficacy and their lack of side effects, these novel lipopeptide adjuvants provide a substitute for many conventional adjuvants. PMID- 1439137 TI - Inert carriers for immunization. PMID- 1439139 TI - Non-inflammatory peptide fragments of IL1 as safe new-generation adjuvants. PMID- 1439138 TI - Biodegradable poly(DL-lactide-co-glycolide) microspheres. PMID- 1439140 TI - Adjuvant-independent induction of immune responses by antibody-mediated targeting of protein and peptide antigens. PMID- 1439141 TI - Mouse T-lymphocyte activation by Urtica dioica agglutinin. I.--Delineation of two lymphocyte subsets. AB - Urtica dioica agglutinin (UDA) is a mouse T-lymphocyte-specific mitogen endowed with proliferative characteristics different from ConA, the prototypic T lymphocyte mitogen. In particular, UDA induces 2-3-fold-reduced thymidine incorporation as compared to ConA. In an attempt to define the basis of this reduced proliferation, we analysed whether UDA binds to a unique subset of T lymphocytes or whether it activates only a T-cell subset. Cytofluorimetric analysis showed that this lectin binds uniformly to all T lymphocytes and does not, on this criterion, distinguish a particular T-cell subset. We next analysed whether UDA provokes the activation of all T lymphocytes. This was carried out by measuring the increase in cell size and the induction of the p55 chain of the IL2 receptor. The analysis showed that, throughout the kinetics of cell activation, only one subset of T lymphocytes increased in size and expressed the p55 chain of the IL2 receptor, suggesting that UDA activates only a subpopulation of T cells. This conclusion was strengthened by the analysis of 5-bromo-2-deoxyuridine (BrdU) incorporation into the DNA of UDA-activated cells. Two populations were easily identifiable: a BrdU-negative subset consisting of all the small p55-negative lymphocytes, and a BrdU-labelled subset including all the large p55-positive cells. BrdU was incorporated in both CD4+ and CD8+ cells, indicating that UDA did not distinguish helper from cytotoxic T lymphocytes. In addition to the p55 chain of the IL2R, all cycling cells expressed the Pgp-1 activation marker. The T lymphocytes, which bound UDA but did not proliferate, remained fully susceptible to subsequent stimulation by ConA. In conclusion, the capacity to proliferate upon UDA binding differentiates a UDA-sensitive from a UDA-refractory subset among splenic mouse T lymphocytes. PMID- 1439142 TI - Mouse T-lymphocyte activation by Urtica dioica agglutinin. II.--Original pattern of cell activation and cytokine production induced by UDA. AB - Urtica dioica agglutinin (UDA) is a T-lymphocyte-specific polyclonal activator that differs from ConA, the classical mouse T-cell mitogen, by inducing a late and limited proliferation of a distinct T-cell subset recruited among both CD4+ and CD8+ lymphocytes. We investigated the possibility that the particular kinetics may originate from UDA-specific activation processes in which the known early mandatory signals were completed only after an extended delay. We report that the time of contact required between lectin and the cell membrane to acquire the capacity to proceed into cell cycle was much longer (36-40 h) for UDA than for ConA (8-10 h). Addition of phorbol ester, which artificially induces PKC translocation, or ionomycin, which provokes Ca2+ mobilization, did not accelerate the proliferative kinetics, suggesting that these early mandatory signals are not the limiting factors in the delayed proliferation. The induction of c-myc was retarded in the UDA group, and there was a good correlation between the kinetics of c-myc induction and the kinetics of cell proliferation. The comparison of the level of transcription of the genes encoding different cytokines revealed additional differences between the two mitogens: the whole wave of cytokine gene expression was delayed with UDA. In particular, IL2, IL3 and IFN gamma gene expression was retarded compared to the ConA-induced single wave. An even later transcriptional wave took place at around 72 h for IL4 and IL5. Finally, this particular kinetics corresponded to an unusually high level of IL3 and IFN gamma and a low level of IL4 and IL5 gene transcripts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439143 TI - Analysis of heavy and light chain use of lupus-associated anti-La/SS-B and anti Sm autoantibodies reveals two distinct underlying immunoregulatory mechanisms. AB - The immunoregulatory mechanisms involved in autoimmune diseases are still unclear. One approach to elucidating these mechanisms involves evaluation of the clonality of the lymphocytes involved in autoimmunity. Molecular analysis of the rearrangement patterns of antigen receptor genes in T cells and B cells has produced ambiguous results. The present study focuses on the analysis of the autoantibodies themselves, being the end products of autoimmune reactivity. Heavy and light chain use of autoantibodies and of total IgG was determined in sera containing anti-La/SS-B and/or anti-Sm antibodies, two autoantibody specificities associated with rheumatic diseases such as systemic lupus erythematosus and Sjogren's syndrome. From our experiments, the anti-La/SS-B response emerges as an oligoclonal, IgG1-restricted B-cell response associated with sharply elevated levels of total serum IgG1-kappa. These characteristics are in sharp contrast to the polyclonal, IgG-subclass-unrestricted anti-Sm response which is accompanied by normal or slightly elevated total serum IgG levels. These findings suggest that anti-La/SS-B autoantibodies, in contrast to anti-Sm autoantibodies, are the product of a restricted oligoclonal B-cell response and thus may be the consequence of a (virally triggered) benign B-cell lymphoma. PMID- 1439144 TI - Molecular biology and immunology of interleukin-6. PMID- 1439145 TI - Regulation of IL6 gene expression. PMID- 1439146 TI - IL6 signalling through IL6 receptor and receptor-associated signal transducer, gp130. PMID- 1439147 TI - IL6 and the T-cell response. PMID- 1439148 TI - Effects of IL6 on B cells in mucosal immune response and inflammation. AB - Freshly isolated surface IgA+ (sIgA+) B cells from human gut-associated lymphoreticular tissues (GALT), e.g. the appendix, express high levels of IL6 receptor (IL6R) and respond to IL6 with significant increases in the number of IgA-secreting cells. On the other hand, neither sIgM+ nor sIgG+ B cells from appendix express IL6R. When the effect of IL6 on IgA subclass antibody synthesis was examined, the numbers of both IgA1- and IgA2-producing cells were increased upon incubation of GALT B cells with IL6; however, 60-70% of IgA-secreting cells were IgA2 subclass. Aberrant local production of IL6 can contribute to increased B-cell responses that occur in mucosal inflammation such as gingiva of patients with adult periodontitis (AP). When gingival mononuclear cells (GMC) isolated from AP patients were cultured without any stimulus, GMC spontaneously produced biologically active IL6 which induced peripheral blood mononuclear cells (PBMC) from the same patients to become IgG- and IgA-producing cells. Further, mRNA extracted from GMC possessed high message for IL6. When the expression of IL6R was compared between GMC and PBMC isolated from AP patients, IL6R-bearing cells were only seen in the former population. Thus, a high production of IL6, which have the ability to regulate later stages of IL6R+ B-cell development and to induce them to become Ig-secreting plasma cells and to support plasmacytoma growth, are important immunopathological elements for the induction of the increased B-cell response region in inflamed mucosal tissues. PMID- 1439149 TI - IL6 and haematopoietic stem cells. PMID- 1439150 TI - IL6 and thrombocytopoiesis. PMID- 1439151 TI - IL6 and the acute phase reaction. PMID- 1439152 TI - Interleukin 6 and autoimmunity and plasma cell neoplasias. PMID- 1439153 TI - IL6 and AIDS. PMID- 1439154 TI - Growth regulatory functions of IL6 and antitumour effects. PMID- 1439155 TI - Clinical applications of IL6 inhibitors. PMID- 1439156 TI - Clinical application of IL6 in cancer therapy. PMID- 1439157 TI - Parental and peer influences on leisure-time physical activity in young adolescents. AB - Influence from parents and friends on adolescents' self-reported level of leisure time physical activity was examined through measures of (a) perceived leisure time physical activity of parents and best friend, (b) perceived direct support for physical activity from parents and friends, (c) direct help from parents in exercising vigorously, and (d) perceived value of physical activity of parents and friends. The present analysis included 904 students in western Norway (M age 13.3 years, SD 0.3) who took part in a health behavior survey, which included questions regarding physical activity. Students completed a confidential questionnaire at school. All four measures of influence were positively related to students' activity levels. None of the examined measures was clearly stronger than the other. Parental and peer physical activity level and parental and peer support for physical activity seem to influence the reported physical activity level of the respondents. The findings indicate that, by serving as models and supporters, significant others have an important impact in promoting physical activity in young adolescents. PMID- 1439158 TI - Children's one-hand catching as a function of age, gender, and ball location. AB - A sizable body of literature exists on the product characteristics and developmental sequence for two-hand catching, but to date there is no description of the developmental characteristics of simple one-hand catching in young children. This study investigated the influence of age, gender, and ball location on children's one-hand catching. Boys and girls (N = 240) ranging in age from 5 to 12 years attempted to catch a total of 24 tennis balls, tossed from a 9-ft distance. Tosses were directed to four locations: (a) Waist, (b) Shoulder, (c) Above-the-Head, and (d) Out-to-the-Side. Descriptive data consisted of the percentage of successful catches at each ball location, and the hand-arm orientation selected by the child as a function of ball location. Results revealed that catching performance improved with age, boys caught more balls than girls, ball location influenced catching success, and, in general, the location of the toss constrained the child's selection of an appropriate hand-arm orientation. With the possible exception of the Shoulder location for girls, even very young children are sensitive to the perceptual aspects of the toss and respond with an appropriate orientation. PMID- 1439159 TI - Effects of violating local independence on IRT parameter estimation for the Binomial Trials Model. AB - The appropriateness of the Binomial Trials Model for test data that consist of multiple attempts of the same item needs to be determined because the presence of learning or fatigue effects may violate the model's assumption of local independence. The purpose of this study was to determine what effect the severity of the violation of local independence (VLI), coupled with different sample size (SS), test length (TL), and test difficulty (TD) had on the estimation of the model difficulty parameter, b, using computer simulation techniques. Each of the following conditions was replicated 100 times under a completely crossed design: SS (100, 200, 500, 2,000); TL (5, 10, 20, 25 attempts); TD (-1.2, 0.0, 1.2); and VLI (from no violation to complete violation). Examinee ability or latent trait was pseudorandomly drawn from a standard normal distribution, and the b-parameter was estimated using a maximum likelihood procedure on generated test scores. Regardless of SS, TL, and TD, the b-parameter tended to be overestimated for situations in which the VLI condition simulated fatigue and underestimated when the VLI condition simulated late-test learning or practice effect. The findings suggest that violations of local independence, at least as simulated in this study, could seriously bias the difficulty parameter estimates if all examinees tested exhibited the dependency. PMID- 1439160 TI - The reliability and validity of the 20-meter shuttle test in American students 12 to 15 years old. AB - The purpose of this study was threefold: to determine (a) the test-retest reliability of the 20-m shuttle test (20 MST) (number of laps), (b) the concurrent validity of the 20 MST (number of laps), and (c) the validity of the prediction equation for VO2max developed by Leger, Mercier, Gadoury, and Lambert (1988) on Canadian children for use with American children 12-15 years old. An intraclass coefficient of .93 was obtained on 20 students (12 males; R = .91 and 8 females; R = .87) who completed the test twice, 1 week apart (MT1 = 47.80 +/- 20.29 vs. MT2 = 50.55 +/- 22.39 laps; p > or = .13). VO2peak was obtained by a treadmill test to volitional fatigue on 48 subjects. The number of laps run correlated significantly with VO2peak in males (n = 22; r = .65; F [1, 20] = 14.30 p < or = .001), females (n = 26; r = .51; F [1, 24] = 8.34; p < or = .01), and males and females = (r = .69; F [1, 46] = 42.54, p < or = .001). When the measured VO2peak (M = 49.97 +/- 7.59 ml.kg-1.min-1) was compared with the estimated VO2max (M = 48.72 +/- 5.72 ml.kg-1.min-1) predicted from age and maximal speed of the 20 MST (Leger et al., 1988) no significant difference was found, t (47) = -1.631; p > or = .11, between the means; the r was .72 and SEE was 5.26 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439161 TI - Age-related differences in the control of spatial aiming movements. AB - The experiment was designed to (a) examine age-related differences in the control of aiming movements, and (b) determine the locus of slowing in movement execution of older adults. Fitts's (1954) index of difficulty (ID) was used to manipulate movement execution demands, and kinematics were used to examine the response characteristics. Twelve young and 12 older adults performed simple aiming movements 10 cm or 20 cm in amplitude to targets of 0.5 cm, 1.0 cm, or 2.0 cm in width, resulting in IDs ranging from 3.32 to 6.32. The results for both young and older subjects support the prediction that movement time (MT) increases as a function of ID and that older adults are significantly slower and more affected by increases in ID than the young adults. Velocity and acceleration profiles of the older adults' movements displayed very different response characteristics than those of the young adults. The results suggest that older adults emphasize accuracy of response and are concerned with the latter phase of the movement in order to contact a target accurately. PMID- 1439162 TI - A comparison of modeling modalities in the observational learning of an externally paced skill. AB - This study contrasted prepractice modeling with either the perceptual component (perceptual modeling) or the motor component (movement pattern) of a coincident timing task to determine whether experiencing the modalities singly or in combination enhanced timing performance on initiation of active practice. The motor component was a 60-cm right-to-left arm movement coincident with the illumination of lights on a Bassin timer runway to displace a barrier as the final runway light was illuminated. Four groups were compared (n = 12 per group). A perceptual modeling group passively viewed stimulus runway lights prior to attempting the task. A motoric modeling group viewed a videotape prior to practice of a model performing the motor component of the skill with zero timing error. A perceptual modeling plus motoric modeling group experienced both modeling modalities prior to performance. Finally, a no modeling group simply initiated practice on the task without modeling. Results indicated that the groups experiencing perceptual modeling initiated practice with significantly less average timing error and variability. Thus, perceptual modeling appeared to be at least as important as motoric modeling as a source of prepractice information to make available to a learner to optimize coincident-timing skill acquisition. PMID- 1439163 TI - What undergraduate physical education majors learn during a field experience. AB - Early field experiences and student teaching have a significant impact on the development of prospective teachers' perceptions of teaching and themselves as teachers (Dodds, 1989). The purpose of this study was to describe what happened to physical education majors during a secondary physical education methodology course that included two field experiences in which the undergraduates taught at least one lesson a day. The four research questions that guided the study were (a) What issues did the majors attend to as significant incidents from their teaching, and did these issues change during their field experiences? (b) What were the characteristics of field experience lessons they perceived as successful? (c) What were the characteristics of field experience lessons they perceived as unsuccessful? and (d) What were the physical education majors' conceptions of teaching? Participants in the study were 39 junior-year physical education teacher education majors. Data were collected using the critical incident technique (Flanagan, 1954) and an open-ended, written questionnaire that was designed to encourage the majors to reflect on various aspects of their teaching experience. The questionnaire and critical incidents were analyzed using an inductive analytical procedure and a series of categories developed from several readings of students' writings. The teacher preparation program affected how these trainees defined and evaluated their teaching experiences. In contrast to some of the earlier work in physical education, the results indicated pupil learning, quality lesson planning to ensure pupil learning, and efficient lesson management were major characteristics of successful lessons for these trainees. The trainees presented "theories of knowledge" that emphasized technical concepts of teaching with little attention to the social or ethical dimensions of their work or the content knowledge of their field. Additional research is needed to examine appropriate programmatic efforts to help preservice teachers reflect not only on teaching, learning, and schooling as a technical enterprise but also as a moral and ethical enterprise. PMID- 1439164 TI - Cardiac structure and function in women basketball athletes: seasonal variation and comparisons with nonathletic controls. AB - To characterize hypertrophy and quantify seasonal changes in cardiac structure and function of women collegiate basketball (BB) athletes (n = 15), echocardiographic (echo) measurements were made in the fall (FALL1), winter (WIN), and spring (SPR), then again during the subsequent fall (FALL2; n = 10). Comparisons were made to age-matched nonathletes (NA) measured during FALL1 (n = 22) and SPR (n = 5). Left ventricular (LV) internal dimension-diastole (LVIDd), LV end-diastolic volume (LVEDV), stroke volume (SV), LV mass (LVM), septal thickness (IVS), LV posterior wall thickness (LVPW), right ventricular (RV) internal dimension-diastole (RVIDd), and aortic root diameter (AOD) were significantly larger (12-70%) in the athletes; RVIDd-, LVEDV-, SV-, and LVM-index were also significantly greater (8-46%). From FALL1 to SPR measurement periods, LVIDd, RVIDd, LVEDV, SV, IVS, and LVM-index increased significantly (7-18%) in the athletes. Over the same period of time, LVIDd, LAD, AOD, LVEDV, and SV measured in the five NA subjects increased significantly. In the athletes, LVIDs, RVIDd, IVS, LVPW, and LVM decreased significantly (5-30%) from the SPR to FALL2 measurement period. These data characterize the general nature of the cardiac hypertrophy noted in women BB athletes compared to NA controls and show that distinct changes in heart structure corresponding to different periods of the competitive season can occur in these athletes. PMID- 1439165 TI - Relationship of optical density and skinfold measurements: effects of age and level of body fatness. AB - We examined relationships between skinfold (SKF) and optical density (delta OD) measurements across age and levels of body fatness (%BF) for 151 women, 20 to 72 years. There were significant (p < .05) relationships between delta ODs and SKFs at all sites, except the thigh. The interaction (SKF x Age) was significant (p < .05) for pectoral and biceps delta ODs. Slope comparisons indicated the relationships for younger (29 years) and older (59 years) women differed significantly from zero and each other (p < .05). Analysis of SKF x %BF interactions revealed that relationships between SKFs and delta ODs at the pectoral and biceps sites for leaner (22% BF) women differed significantly from zero (p < .05) and were larger than those for obese (39% BF) women (p < or = .05). Thus, the relationship between SKFs and delta ODs is stronger for younger and leaner women compared to older and fatter women. These findings may reflect differences in fat layering due to age or body fatness and provide insight as to why the manufacturer's near-infrared (NIR) equation significantly underestimates the %BF of obese women. PMID- 1439166 TI - Coping by individuals with physical disabilities with perceived challenge in physical activity: are people consistent? AB - This study examined coping and affective experience to perceived challenge in physical activity settings in 30 individuals with physical disabilities in three separate situations over 6 months. On every occasion, each individual was asked to report the most challenging physical activity of the preceding week and indicate how he or she coped with the challenge and what affective states were experienced. Coping was measured using a modification of Carver, Scheier, and Weintraub's (1989) COPE inventory. Self-reported mood was assessed using the Positive Affect Negative Affect Schedule (Watson, Clark, & Tellegen, 1988). The data indicated that perceived challenge was characterized by high levels of positive affect. Generalizability theory, used to determine the relative stability of coping strategies, indicated that individuals with physical disabilities did not consistently use the same coping skill strategies across settings. PMID- 1439167 TI - The role of sports as a social status determinant for children. AB - This study was designed to examine children's attitudes toward the role of sports in determining social status, as well as the activities in which children prefer to participate. A total of 227 boys and 251 girls in Grades 4, 5, and 6 completed a questionnaire to determine which criteria were most important in determining personal, female, and male popularity. Personal popularity was answered by the girls and boys according to "what would make you well liked by your classmates." Female and male popularity was determined by asking both girls and boys to decide "what would make (girls, for female subjects, and boys, for male subjects) well liked by your classmates." A comparison of results from the Buchanan, Blankenbaker, and Cotten (1976) investigation and the present study indicated that, in the last 15 years, appearance has become more important and academic achievement less important in determining personal popularity for girls. For boys, the comparison revealed that sports have become more important and academic achievement less important in determining personal popularity. Boys reported sports to be the most important determinant of personal and male popularity and appearance as the most important determinant of female popularity. Sports and appearance became more important for boys with each higher grade level. Girls reported appearance to be the most important determinant of personal, male, and female popularity. For girls, appearance became more important with each higher grade level. A comparison of results from the Buchanan et al. (1976) and the present study indicated that the activities in which girls and boys preferred to participate have changed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439168 TI - Correlates of change in walking for exercise: an exploratory analysis. AB - This study was designed to identify correlates of change in walking for exercise. Respondents to a random sample mailed exercise survey were asked to complete a follow-up questionnaire 24 months after the first. Responses were obtained from 1,739 adults, reflecting an 86.6% return rate. Nonrespondents did not differ from respondents for baseline level of walking for exercise. Respondents overrepresented Caucasian and middle to high education (or income) adults. Residualized measures of change in walking for exercise served as the dependent variable, adjusted for baseline walking. Similarly, key independent variables, subject to change over time, were included after residualization. At both baseline and 24 months follow-up, adults walked for exercise an average of just under 1 hour per week, and 23.5% of the initially active adults ceased walking for exercise at 2 years. Multiple regression analyses explained more variance in walking for exercise among women than men. Change in dynamic variables such as friend's support and vigorous physical activity accounted for most of the explained variance. Results suggest that dynamic variables may need to be sustained to maintain walking for exercise. The limited explained variance suggests that more precise measures and additional determinants of walking for exercise need to be identified. PMID- 1439169 TI - Energy costs of self-paced walking with handheld weights. PMID- 1439170 TI - Efficacy of skinfold training clinics: a comparison between clinic trained and experienced testers. PMID- 1439171 TI - The role of pedagogical content knowledge in motor skill instruction: comments and questions on Walkwitz & Lee, 1992. PMID- 1439172 TI - Are American children and youth fit? Some international perspectives. PMID- 1439173 TI - Are American children and youth fit? Some international perspectives. Fitness of 10-year-old youth: a cross-cultural perspective. PMID- 1439174 TI - Formation of multicellular spheroids composed of rat hepatocytes. AB - A novel method for the preparation of spheroids containing two types of cells (hetero-spheroid) has been successfully developed by using a collagen-conjugated thermo-responsive polymer, poly-N-isopropyl acrylamide, as a cell substratum. The hetero-spheroid was prepared by detaching the confluent monolayer composed of parenchymal and non-parenchymal rat liver cells at a temperature below lower critical solution temperature and culturing it on the non-adhesive substratum. The hetero-spheroid had activity in albumin secretion and PNPA hydrolase activity over a period of 60 days in dishes. These findings suggest that this spheroid formation system is a useful model of an alternative to animal tests of hepatotoxicity. PMID- 1439175 TI - Elevation of the level of lipid peroxidation associated with hepatic injury in LEC mutant rat. AB - Long-Evans Cinnamon (LEC) mutant rat, which spontaneously develops a chronically necrotizing hepatic injury at 4-5 months of age, exhibits an excess hepatic copper accumulation. The hepatic injury was completely correlated to the excess hepatic copper accumulation in backcross progenies, supporting the previous hypothesis that the copper cytotoxicity causes the hepatic injury in LEC rat liver. The levels of the lipid peroxidation in symptomatic LEC rats at 4 months of age were significantly higher than those of age-matched asymptomatic LEC and normal rats. These results suggest that excessively accumulated copper provokes hepatic injury through initiating the lipid peroxidation. PMID- 1439176 TI - Effect of the synthetic N-homocysteine thiolactonyl derivatives, thioretinaco, thioretinamide, and thioco on growth and lactate production by malignant cells. PMID- 1439177 TI - Metabolic effects of diltiazem in the perfused rat liver. AB - The effects of diltiazem on oxygen uptake, glucose release, lactate production and pyruvate production in the perfused liver from fed rats were investigated. Diltiazem inhibits oxygen uptake and glycolysis. Glucose release from endogenous glycogen is increased after cessation of diltiazem infusion. The reversion of the inhibitory effects of diltiazem after cessation of infusion takes place very slowly. The compound also abolishes glucose release activation by norepinephrine, methotrexate and atractyloside. These effects seem to be the consequence of a more general effect of the drug on metabolism. It can be concluded that 0.5 mM diltiazem is highly toxic to the liver and that it should not be considered a specific agent against Ca(2+)-dependent hormones. PMID- 1439178 TI - pNiXa, a Ni(2+)-binding protein in Xenopus oocytes and embryos, shows identity to Ep45, an estrogen-regulated hepatic serpin. AB - A Ni(2+)-binding protein (pNiXa, 45 kD, pI 8.5) discovered in Xenopus embryos, was isolated from oocytes. Based on amino acid sequences, pNiXa belongs to the serpin superfamily and shows identity to the cDNA sequence of Ep45, an estrogen regulated hepatic serpin that contains an (HX)n-motif found in eukaryotic transcription factors. Nondenatured pNiXa, purified by Ni-affinity chromatography, inhibited bovine alpha-chymotrypsin. The presence of pNiXa in embryos when they are susceptible to Ni2+, the high avidity of pNiXa for Ni2+, and the (HX)n-motif point to pNiXa as a molecular target of Ni(2+)-teratogenesis. PMID- 1439179 TI - Formation of reductive metabolite, 2-sulfamoylacetylphenol, from zonisamide in rat liver microsomes. AB - Zonisamide (1,2-benzisoxazole-3-methanesulfonamide) was metabolized to its reductive product, 2-sulfamoylacetylphenol, in rat liver microsomes under anaerobic conditions. The rate of NADPH-dependent reaction was much more rapid than that of NADH-dependent reaction. Furthermore, synergistic effect of NADH on NADPH-dependent reaction was not observed. The optimal formation of 2 sulfamoylacetylphenol from zonisamide in the presence of NADPH was observed around pH 7.0. Cimetidine showed an inhibitory effect on the formation of 2 sulfamoylacetylphenol in a dose-dependent manner. The reductive metabolism of zonisamide was almost completely inhibited by carbon monoxide, and was increased by pretreatment of rats with phenobarbital and pregnenolone 16 alpha-carbonitrile but not by pretreatment with ethanol, 3-methylcholanthrene and imidazole. These results suggest that phenobarbital- and pregnenolone 16 alpha-carbonitrile inducible form(s) of cytochrome P-450 is responsible for the reductive metabolism of zonisamide to 2-sulfamoylacetylphenol in rat liver microsomes. PMID- 1439180 TI - Serum amino acid levels and hepatic protein synthesis during liver regeneration after partial hepatectomy in rats. AB - The time courses of changes in serum concentrations of free amino acids and in hepatic protein synthesis during liver regeneration after partial hepatectomy were studied in rats. Hepatic protein synthesis was significantly higher 3, 5 and 7 days after partial hepatectomy than it was in sham-operated control rats, but there was no such difference 14 days after surgery. Serum total amino acid level was significantly higher in partially-hepatectomized rats than in control rats 3 days after surgery, and thereafter decreased slowly. By 7 days after surgery there was no significant difference between the two groups. Serum concentrations of threonine, serine, proline, histidine, tyrosine, methionine, ornithine and citrulline were significantly higher than in the control group 3 days after partial hepatectomy, and the concentrations of proline, histidine, tyrosine, methionine and ornithine were still high 5 days after surgery. In contrast, concentrations of branched-chain amino acids did not change. PMID- 1439181 TI - Relationship among cardiac sympathetic nerve activity, blood pressure and heart rate during infusion of carperitide in rats. AB - The effect of the infusion of carperitide (alpha-human atrial natriuretic peptide; alpha-hANP) on cardiac sympathetic nerve activity, blood pressure and heart rate was studied in anesthetized rats. Intravenous infusion of carperitide (0.1 and 1.0 micrograms/kg/min) produced mild and dose-related decreases in mean arterial pressure without significant changes in cardiac sympathetic nerve activity or heart rate. In debuffered rats, carperitide (1.0 micrograms/kg/min) also produced a mild decrease in mean arterial pressure. No significant changes in cardiac sympathetic nerve activity or heart rate were observed. A significant correlation between changes in heart rate and cardiac sympathetic nerve activity was noted during infusion of carperitide and deafferentation did not alter this relationship. In contrast, no significant correlation was observed between changes in cardiac sympathetic nerve activity and blood pressure during infusion of carperitide in either buffer nerve intact or debuffered rats. These results suggest that the reduction of blood pressure induced by intravenous infusion of carperitide may not trigger the baroreceptor-mediated cardiac sympathoexcitation and this inhibition of baroreflex may be responsible for the anti-tachycardic effect of carperitide. PMID- 1439182 TI - The anti-asthmatic agent KC 404 inhibits sodium absorption by canine tracheal epithelium. AB - To elucidate the effect of KC 404, an anti-asthmatic agent, on electrolyte transport across airway mucosa, we studied electrical properties of canine tracheal epithelium under isometric conditions in vitro. Addition of KC 404 decreased short-circuit current, transepithelial potential difference and cell conductance, accompanied by the decrease in 22Na flux from submucosa to mucosa. The KC 404-induced decrease in short-circuit current was inhibited by amiloride but not by diphenylamine-2-carboxylate. These results suggest that KC 404 selectively inhibits Na absorption by airway epithelium, thereby leading to the increase in water content in the respiratory lumen. PMID- 1439183 TI - An evaluation of 2-benzyl-1-naphthol (DuP 654) analogs as systemic anti inflammatory agents. AB - DuP 654 (2-benzyl-1-naphthol) is a topically active anti-inflammatory agent that was evaluated in phase II clinical trials as an anti-psoriatic agent. The compound is a potent 5-lipoxygenase inhibitor and exhibits inhibitory activity against lipopolysaccharide-stimulated release of interleukin-1 from human monocytes. DuP 654 cannot be used as a systemic anti-inflammatory compound due to its rapid and extensive metabolism. Fifteen analogs were synthesized in an attempt to block the systemic route(s) of metabolism. The compounds were evaluated (IP and PO) in the rat carrageenan paw edema inflammation model with plasma samples taken at 1, 2, 3, and 4 hours post-dose. Substitutions at the 4- and/or 8-positions on the naphthol, and/or on the benzyl group of the DuP 654 molecule were unsuccessful in achieving an analog which displayed both oral activity in the inflammatory model and high plasma levels without manifesting toxicity. The low plasma levels of some analogs may indicate poor absorption, high volume of distribution, or that the substitution did not inhibit the high hepatic "first-pass" metabolism observed with DuP 654. Other compounds not studied but similar in structure to DuP 654 may exhibit rapid and extensive metabolism. PMID- 1439184 TI - Concurrent ingestion of lactate and aluminum can result in developmental toxicity in mice. AB - The influence of lactate on the potential developmental toxicity of high doses of aluminum (57.5 mg/kg/day) was evaluated. Three groups of pregnant Swiss mice were given by gavage daily doses of Al(OH)3 (166 mg/kg), aluminum lactate (627 mg/kg), or Al(OH)3 (166 mg/kg) concurrent with lactic acid (570 mg/kg) on gestational days 6-15. An additional group of pregnant mice received lactic acid (570 mg/kg) during the same period. Cesarean sections were performed on gestation day 18, and live fetuses were sexed, weighed and examined for morphological defects. Maternal toxicity was observed in the groups treated with aluminum lactate, and Al(OH)3 concurrent with lactic acid. The reproductive data did not show embryotoxic effects in any group, whereas fetal body weight was significantly reduced in the aluminum lactate group. In this group, morphological changes included cleft palate and an increased incidence of parietals with delayed ossification. Although not statistically significant, the incidence of skeletal variations was also increased in the group given Al(OH)3 concurrent with lactic acid. Taken together the present data, as well as the results of previous studies strongly suggest that the consumption of high doses of aluminum-containing compounds should be avoided during pregnancy. PMID- 1439185 TI - Cell-to-cell communication in cultured rat thyroid monolayer cells is inhibited dose-dependently by methimazole. AB - We performed monolayer culture of rat thyrocytes and studied gap junctional communication by measuring intercellular fluorescence redistribution after photobleaching. Cell-to-cell communication among thyrocytes gradually developed during the culture. This communication was demonstrated in approximately 60 percent of the cells cultured for 8 days, while it could not be detected in the remaining 40 percent of the cells even after longer culture. When thyrocytes were cultured in the presence of methimazole, the fluorescence recovery after photobleaching was inhibited dose-dependently. Thyroid-stimulating hormone did not affect the fluorescence recovery. We provided, for the first time, that methimazole inhibited the development of cell-to-cell communication of thyrocytes dose-dependently. PMID- 1439186 TI - Influence of a stable prostacyclin analogue, Cicaprost, on the response to prostaglandin F2 alpha in the perfused human placenta. AB - Because a balance between the vasodilator effect of Prostacyclin and the vasoconstrictor effect of Prostaglandin F2 alpha (PGF2 alpha) may be necessary for the regulation of utero-placental-fetal blood flow, a study was designed to assess the influence of a stable prostacyclin analogue, Cicaprost, on the response to Prostaglandin F2 alpha in the perfused human placenta. Cicaprost produced a dose-dependent inhibition of the pressor response of 50 mcg of PGF2 alpha. The decrease in PGF2 alpha-induced pressor response by 0.1 mcg of Cicaprost was not significant, only 6.95 +/- 8.2%. However, 0.5 mcg and 1.0 mcg of Cicaprost significantly attenuated the pressor response of PGF2 alpha by 36.6 +/- 9.5% and 46.8 +/- 8.3%, respectively (MEAN +/- S.E.). PMID- 1439187 TI - Quantitative determination of 17 beta-estradiol and progesterone in cellular fractions of term placentae of normal and hypertensive patients. AB - During pregnancy the placenta is both the source and target for the actions of steroid hormones. In fact, an intact feto-placental unit is capable of elaborating increasing levels of a wide variety of steroid hormones and many other substances. The falling levels of steroid hormones, like estrogens and progesterone in serum and urine have been reported during pregnancy induced hypertension and/or preeclampsia. The purpose of this study was to determine the concentration of 17 beta-estradiol and progesterone in cytosol, nucleic fraction and particulate fraction of term placentae of normal and hypertensive patients by radioimmunoassay. Data from this study reveal the concentrations of 17 beta estradiol (E2) and progesterone (P) in various cellular fractions from six placentae of normal patients (NP) and five placentae of hypertensive patients (HP). In HP overall concentrations of E2 (75.8 ng/gm) and P(46.5 micrograms/gm) is greater than those in NP, 32.6 ng/gm and 25.0 micrograms/gm respectively. The concentration of E2 in nuclear fraction of NP and HP remains unchanged while P concentration of nuclear fraction of HP (25.4 micrograms/gm) is much greater than those of NP (8.8 micrograms/gm). Moreover, the E2 concentration (55.5 ng/gm) in cytosol of HP is much greater than those of NP (12.3 ng/gm). Therefore, this study indicates that the abnormal concentrations of E2 and P of placentae are associated with pregnancy induced hypertension. PMID- 1439188 TI - Inhibition of [3H]-MK801 binding and protection against NMDA-induced lethality in mice by a series of imipramine analogs. AB - A series of imipramine analogs were tested for inhibition of [3H]-MK801 binding and for their ability to protect against NMDA-induced lethality in mice. The structure-activity relationship (SAR) for the inhibition of [3H]-MK801 binding found primary amines on short linkers to be optimum. For protection against NMDA lethality, compounds containing an unsaturated link to a cyclic amine were the most potent analogs tested. Possible explanations for the lack of correlation observed are briefly discussed. PMID- 1439189 TI - Serum and organ indices of the mdx dystrophic mouse. AB - Duchenne muscular dystrophy (DMD) is a fatal disease for which there is no effective treatment. The cause of death in patients with DMD is often cardiovascular and pulmonary dysfunction. This clinical observation, combined with experimental findings, suggests that other non-muscle organ systems may be affected in the dystrophic disease state. To test this hypothesis, the present study investigated liver and kidney function in the mdx mouse. Serum chemistries and the hepatic cytochrome P-450 system in normal and dystrophic mdx mice were investigated at two different ages. Increases in serum lactate dehydrogenase (LDH), alkaline phosphatase (AP), aspartate transaminase (AST), and cholesterol levels, combined with an increase in liver weight and a decrease in cytochrome P 450, suggests the possibility of hepatic dysfunction. Increases in serum uric acid and phosphorus, and decreased kidney weight suggest hepatic dysfunction. PMID- 1439190 TI - Plasma concentration of furosemide versus specific gravity of urine in predicting dose of administration in race horses. AB - This study was undertaken to determine the applicability of plasma concentration of furosemide and specific gravity (SG) of urine in regulating the use of furosemide administered 4 hours prior to race time in Exercise-Induced Pulmonary Hemorrhage (EIPH) race horses. Nonbleeders (CTL) and certified bleeders (FUR) actively racing in Illinois (IL) and Pennsylvania (PA) were used in the study. Various doses (less than 250, 250, 300, 350, 400 and 500 mg) were administered either as a single intravenous (IV) dose or as a combination (IV-IM) of IV and intramuscular (IM) administrations 4 hours before race time. Plasma and urine samples were obtained post race for determination of furosemide concentration in plasma and measurement of SG of the urine in both CTL and FUR groups. Plasma samples were analyzed for furosemide using High Performance Liquid Chromatography with Fluorescence Detection. SG was measured using a digital refractometer. The results indicate a significant difference (p less than 0.0001) in the SG of the urine samples between the CTL and FUR groups irrespective of the route of administration (IV versus IV-IM). However, SG values of the urine in some CTL samples were lower than those in some FUR samples and vice versa. Thus, the use of SG alone is not reliable for predicting either the dose or the administration of furosemide to race horses. The plasma concentrations of furosemide following the administration (IV) of 250 mg or 500 mg 4 hours prior to race time were indistinguishable (25.91 +/- 4.45 versus 28.12 +/- 6.99 ng/ml, respectively); the majority of the horses in the groups had a plasma concentration of less than 40 ng/ml. When taken in total, plasma concentration of furosemide can only be used as a guide in regulating the administration of furosemide to race horses. PMID- 1439191 TI - The effects of xanthoangelol E on arachidonic acid metabolism in the gastric antral mucosa and platelet of the rabbit. AB - The effects of a new chalcone derivative, xanthoangelol E, isolated from Angelica keiskei Koidzumi, on arachidonic acid metabolism in the gastric antral mucosa and platelet of the rabbit were examined. When gastric antral mucosal slices were incubated with xanthoangelol E (0.05-1.0 mM), there was no significant effect on the production of prostaglandin (PG) E2, PGF2 alpha and their metabolites. On the other hand, this compound inhibited effectively the production of thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid from exogenous arachidonic acid in platelets, and the concentration required for 50% inhibition (IC50) was approximately 5 microM. The formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid was also reduced by this drug (IC50, 50 microM). These results suggest that xanthoangelol E has the potential to modulate arachidonic acid metabolism in platelets and that this action may participate in some pharmacological effect of the plant. PMID- 1439193 TI - Direct membrane damage and miconazole lethality. AB - Physicochemical membrane damage is presumably the cause of growth phase-dependent lethal miconazole action. In support of this, we showed that as stationary phase inoculum cells of Candida albicans progress into early logarithmic phase, susceptibilities to lethal action and to miconazole-induced release of K+ increase together. PMID- 1439192 TI - Toxic response of linoleic acid anilide in female rats. AB - The toxicity of linoleic acid anilide (LAA) and heated linoleic acid anilide (HLAA) was studied in female rats. Female Sprague-Dawley rats were given 250 mg/kg of LAA or HLAA in mineral oil, by gavage, on alternate days for two weeks. Control rats received an equal volume of mineral oil. The animals were sacrificed at day 1, 7 and 28 following the last dose. Organ-to-body weight ratio was increased for spleen in both LAA and HLAA treated rats at day 1. Lung, kidney and brain showed increases in this ratio at some time point, whereas, thymus in the HLAA group showed a decrease at day 28. Among blood parameters, red blood cells and hemoglobin content decreased in both LAA and HLAA treated groups at day 1 and in the LAA group at day 7. Serum IgA levels increased throughout the study in both treatment groups and were more pronounced in HLAA treated rats. Splenic T helper lymphocyte numbers decreased in the HLAA group at day 1, whereas, other cell types were not affected. The changes observed in female rats are comparable to our previous findings in male rats and relatively minor in relation to sex differences. These results further support that hemopoietic system is an early target of fatty acid anilide toxicity. PMID- 1439194 TI - Na(+)-Ca2+ exchange influences halothane and caffeine contractures of malignant hyperthermic skeletal muscle. AB - These experiments sought to determine the influence of sarcolemmal Na(+)-Ca2+ exchange on halothane and on caffeine contractures of malignant hyperthermic (MH) skeletal muscle. Fiber bundles excised from MH susceptible pigs (Pietrain) were exposed to halothane (3%) and caffeine (0.5-8.0mM) while Na(+)-Ca2+ exchange was inhibited by reducing extracellular Na+ from 100% to 50, 25 and 0% of control. Halothane contracture magnitude was not altered by 50 or 25% Na+ whereas 0% Na+ increased the contractures by 51%. 0 and 25% Na+ increased the magnitude of caffeine contractures (2-8mM) by 53-176%. These results suggest that external Na+ and the Na(+)-Ca2+ exchange mechanism influences contractures of MH skeletal muscle. PMID- 1439195 TI - Bioartificial endocrine pancreas: foreign-body reaction and effectiveness of diffusional transport of insulin and oxygen after long-term implantation of hollow fibers into rats. AB - Foreign body reaction of the liver, kidney, and subcutaneous tissue of rats after implantation of hollow fibers (HF) for 1, 3, 6, and 12 months and its influence on the effectiveness of diffusional transport of insulin and oxygen were investigated. The highest degree of fibrosis was observed after subcutaneous implantation of HF and the lowest degree after implantation into the kidney. Histochemical staining of the fibrous capsule showed a tissue-dependent domination of the collagenous fibrils. After 90 min of perfusion 33% of the insulin contained in HF diffused out of the nonimplanted fiber, after 120 min, 73% and after 180 min, 100%. Hollow fibers, which were removed with a surrounding connective capsule after an implantation period of 1 year, showed even better permeability for insulin than nonimplanted HF. The tension of oxygen in the lumen of the implanted hollow fibers was 42 mm Hg after implantation into the kidney and 30 mmHg after implantation into the liver. The oxygen present inside an HF that is implanted into a kidney and liver was consumed by 100 islets in 3.9 and 2.8 min, respectively. It was concluded that to achieve acceptable results in the construction of bioartificial pancreas more research activities should be performed on the diffusion and consumption of oxygen in the bioreactor. PMID- 1439196 TI - beta-Alanyl-L-histidinato zinc prevents hydrocortisone-induced disorder of bone metabolism in rats. AB - The preventive effect of beta-alanyl-L-histidinato zinc (AHZ) on osteopenia was investigated in rats treated with hydrocortisone. Rats received hydrocortisone (75 mg/kg body weight per day) s.c. for 30 days. The steroid treatment caused a significant increase in serum alkaline phosphatase activity and parathyroid hormone (PTH-c) level, while serum calcium, inorganic phosphorus, and zinc concentrations were not significantly altered. The femoral-diaphyseal alkaline phosphatase activity, deoxyribonucleic acid (DNA), and calcium contents were significantly decreased by the treatment of steroid, although the bone zinc content was not appreciably altered. When AHZ (10, 30, and 100 mg/kg per day) was administered p.o. for 30 days to rats giving the steroid, the dose of AHZ (30 and 100 mg/kg) completely prevented the increases in serum alkaline phosphatase activity and PTH-c level and the decreases in femoral-diaphyseal alkaline phosphatase activity, DNA, and calcium contents caused by the steroid treatment. The dose of AHZ (10, 30, and 100 mg/kg) significantly increased zinc content in the femoral diaphysis. Present results indicate that the dose of AHZ can prevent the disorder of bone metabolism caused by hydrocortisone treatment. AHZ may have a therapeutic role in the steroid-induced osteopenia. PMID- 1439197 TI - Effect of isoproterenol on regional myocardial segment work, O2 consumption, and oxygen balance. AB - We tested the hypothesis that positive inotropic stimulation by isoproterenol alters the relationship between regional segment work and regional myocardial oxygen consumption. Regional parameters were compared with external cardiac work and global LV oxygen consumption. In anesthetized open-chest dogs, regional myocardial segment length (ultrasonic dimension crystals) and force development (miniature force transducer) were measured. The integrated multiples of myocardial shortening by corresponding force during an averaged beat expressed segment work (area under the systolic portion of the length-force loop). External cardiac work was calculated from aortic blood pressure and cardiac output. Global and regional myocardial MVO2 were evaluated at baseline and during intravenous infusion of isoproterenol (0.5 and 1.0 micrograms/kg per min). Regional coronary blood flow was measured with radioactive microspheres, and microspectrophotometry of frozen myocardial biopsies was used to evaluate O2 saturation in small arteries and veins. These parameters were used to calculate regional MVO2. Arterial and coronary sinus O2 saturation was used to calculate global LV O2 consumption. Regional myocardial O2 balance was estimated by measurement of NADH redox level using surface fluorometry. It was found that 0.5 micrograms/kg per min isoproterenol increased regional segment work/minute from 4650 +/- 495 to 6750 +/- 750 mm.g/min. Corresponding regional oxygen consumption was disproportionately increased from 5.43 +/- 0.61 to 15.24 +/- 1.37 ml/min per 100 g. External cardiac work was found to decrease from 728 +/- 13 to 562 +/- 25 mmHg.1/min (due to decreased aortic blood pressure), whereas global myocardial O2 consumption increased. Regional myocardial O2 extraction and NADH fluorescence were elevated, indicating impaired tissue oxygenation. Regional MVO2 was increased by 153 +/- 56%, but regional work by only 45.3 +/- 33% (P < 0.05). These results indicate that regional contraction efficiency was markedly reduced by isoproterenol. PMID- 1439198 TI - Cardiac glycosides in the treatment of experimental overdose with calcium blocking agents. AB - The ability of digitalis compounds to counteract calcium antagonist overdose was studied in anesthetized dogs (n = 6, 13.5 +/- 0.7 kg) and isolated trabeculae from human hearts (n = 7). Digitalis caused by increasing intracellular cytosolic Ca2+ concentration through Na+/Ca(2+)-exchange across the cell membrane, was postulated to overcome the detrimental effects of excessive slow calcium-channel blockade. In anesthetized dogs, an infusion of verapamil (40 mg/30 min, i.v.) decreased mean arterial pressure from 88 +/- 6 to 66 +/- 6 mm Hg (P < 0.05), reduced systemic vascular resistance (SVR) from 3838 +/- 916 to 2200 +/- 669 dyne.s/cm5 (P < 0.05), and induced total atrio-ventricular (A-V) block in three animals. Stroke volume (SV) remained unchanged. Administration (i.v.) of NaCl (0.9%, 200 ml) and calcium gluconate (100 mg)--to increase the availability of Na+ and Ca(2+)--together with atropine (0.2 mg)--to block the parasympathetic effects of digoxin on A-V conduction--increased left ventricular contractility (15%) but had no significant effects on blood pressure, SV, or A-V block. Digoxin (0.125 mg) returned sinus rhythm in all dogs and, by increasing SVR (P < 0.05) and left ventricular contractility (P < 0.05), returned arterial pressures to baseline. Because of increased afterload, SV decreased slightly (15%) despite increased cardiac contractility. In experiments with isolated trabeculae from diseased human hearts, TA 3090 (Clentiazem) depressed contractile force and ouabain, another glycoside, restored contractile force within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439199 TI - Simulated weightlessness and bone metabolism: gravitational stimulation enhances insulin sensitivity. AB - The effect of simulated weightlessness on bone metabolism was investigated in skeletal unloading for 4 days. Skeletal unloading was designed using the model of hindlimb hang in rats. Skeletal unloading with hindlimb hang cased a significant decrease of alkaline phosphatase activity, deoxyribonucleic acid (DNA) content, and glucose consumption in the femoral diaphysis, but not in the calvaria. When femoral-diaphyseal tissues were cultured in the presence of insulin (10(-8) M), the hormone produced a significant increase of alkaline phosphatase activity and decrease of glucose consumption in the femoral-diaphyseal tissues obtained from normal rats. This hormonal effect was not seen in the femoral diaphysis, but in the calvaria, of rats with skeletal unloading. However, insulin effect was seen in the femoral diaphysis obtained at 3 days after the removal of skeletal unloading. Meanwhile, the presence of other bone-regulating factors (10(-8) M parathyroid hormone [1-34] and 10(-4) M zinc sulfate) revealed an appreciable effect on alkaline phosphatase activity in the femoral diaphysis from rats with skeletal unloading. These results suggest that gravitational stimulation can directly enhance a specific insulin sensitivity in the regulation of bone metabolism. PMID- 1439200 TI - Gastric mucosal blood flow distribution in the CCl4-induced cirrhotic rat--a model of portal hypertensive gastropathy? AB - Because the carbon tetrachloride-induced cirrhotic rat model is considered to be the closest to the clinical situation of the cirrhotic patient, the discovery of congestive gastropathy in such rats would enable the development of a useful research model. By the use of laser-Doppler technology, gastric mucosal blood flow was assessed on 14 defined points of the stomach in 16 cirrhotic and 16 matched healthy rats, in an effort at in vivo mapping of the gastric mucosal microcirculation. Our findings of mucosal congestion in the cirrhotic stomach (reduced mucosal blood flow in the gastric corpus) are well matched with the distribution of gastric mucosal blood flow in the cirrhotic patient. These findings suggest that a rat's gastric mucosa could be used for studies of portal hypertensive gastropathy. PMID- 1439201 TI - Genetic variation in resistance to parasitic infection: experimental approaches and practical applications. AB - Parasitic infections remain a major threat to the successful maintenance of domestic livestock. Control is still centered around management and husbandry, and the use of chemotherapeutic compounds. However, the spread of drug resistance in many important protozoal and helminth infections is placing an increasing emphasis on the development of alternative forms of control. At the present time vaccination is available for only a limited number of parasites, and may never be practical or cost-effective for some of the most important infections. This review examines current views of the mechanisms, control and likely value of genetically determined differences in resistance to parasitic infection. There is an extensive literature dealing with experimental analyses of genetic variation to parasitic infection in both laboratory and domestic species, and a growing interest in the application of this information in the field of practical parasite control. PMID- 1439202 TI - Transdiaphragmatic pressure measurement in cattle: technical data. AB - Techniques and methods required for accurate and reproducible measurements of transdiaphragmatic pressure (Pdi), were studied in seven-week and five-month-old calves. Since reliable pleural pressure measurement in cattle has already been described, separate experiments were conducted to compare retrodiaphragmatic pressures measured (i) with balloon-catheters and needle catheters, (ii) before and after eructation and (iii) in the ruminal and in the peritoneal cavities. Whereas respiratory-induced pressure changes were equally transmitted throughout the rumen content, a marked anteroposterior damping was observed as the recording site in the abdominal cavity was moved away from the diaphragm (P < 0.0001). It was concluded that the most appropriate and accurate way to measure Pdi changes in polygastric animals is to measure the pressure changes existing in the mid thoracic portion of the oesophagus and in the liquid content of the rumen with balloon-tubing units. Neither growth- and diet-related rumen enlargement nor eructation, which are two typical characteristics of ruminants, altered the reliability of retrodiaphragmatic pressure measurements in the two age groups studied. PMID- 1439203 TI - Application of a diagnostic DNA probe for the differentiation of the two types of Mycoplasma mycoides subspecies mycoides. AB - Contagious bovine pleuropneumonia (CBPP), which is caused by Mycoplasma mycoides subspecies mycoides, is still a serious disease in some parts of the world. There is also a commonly occurring mycoplasma which is sufficiently related to the CBPP organism to bear the same name, even though this organism does not cause CBPP. Thus it is very important to be able to distinguish between these organisms and identify either with certainty. Fragments derived from M mycoides subspecies capri by restriction enzyme digestion of genomic DNA were cloned into the vector M13mp8. One resulting clone CAP-21, with a 1.5 kb insert was used as a probe in Southern hybridisation assays where genomic DNA was digested with the restriction endonuclease TaqI. This probe could differentiate a strain of M mycoides subspecies mycoides which does not cause CBPP. Subsequent tests on 14 other strains from cattle and goats showed that although they were isolated from diverse geographical areas, CAP-21 could clearly differentiate between these two types of M mycoides subspecies mycoides. PMID- 1439204 TI - Interspecies variations in plasma half-life of ampicillin, amoxycillin, sulphadimidine and sulphacetamide related to variations in body mass. AB - The relationships between the half-lives during the elimination phase (t1/2 minutes) of ampicillin, amoxycillin, sulphadimidine and sulphacetamide and body mass (W, kg) between species of mammals and birds were examined using data from the authors' experiments and collected from the literature. Linear regression of the log half-lives of ampicillin, amoxycillin and sulphadimidine following intravenous injection on the log body mass for a variety of species of mammals and birds revealed significant correlations (r = 0.7709, n = 8, r = 0.7712, n = 8, r = 0.7749, n = 10). The interspecies relationships were described by the allometric equations t1/2 = 31.3 W0.16, t1/2 = 32.7 W0.12 and t1/2 = 129.2 W0.28, respectively. These equations may be of value for estimating dose intervals in species for which no relevant pharmacokinetic data are available. PMID- 1439205 TI - Validation of the monofrequency forced oscillation technique for pulmonary function investigation in calves: an in vitro and in vivo study. AB - This study was to investigate whether the monofrequency forced oscillation (MFO) technique could be accurately used for pulmonary function testing in calves. The airflow resistance measured by this technique was compared to the resistance measured by the classical reference method by an in vitro study, using an artificial lung model, and by an in vivo study, using 11 healthy calves. The effect of the reference impedance of this oscillation equipment was also investigated. The results show linear relationships (r2 > 0.924, P < 0.001) in the resistance ranges 0 to 0.7 kPa litre-1 s and 0 to 1.0 kPa litre-1 s with a reference impedance of 1.0 kPa litre-1 s and 2.0 kPa litre-1 s, respectively. The MFO resistance values lower and higher than 0.4 kPa litre-1 s are slightly overestimated and underestimated, respectively. It was shown that, if some technical requirements are met, the MFO technique is a simple, reproducible, fast and accurate method which allows measurement of airflow resistance even in field conditions. PMID- 1439206 TI - Effects of oral sunflower oil and olive oil on serum and cutaneous fatty acid concentrations in dogs. AB - The effects of dietary fatty acids on serum and cutaneous fatty acids of healthy dogs were evaluated under controlled conditions. Beagle puppies (n = 12) were fed a standard diet supplemented with sunflower oil (group A), olive oil (group B) or no supplementation (group C) for 12 weeks. There were no significant differences in food intake or growth rates between the three groups. Dogs in group A had significant increases (P < 0.05) in serum 18:2n6 (linoleic acid) and 20:3n6 (dihomo-gamma-linolenic acid), and cutaneous 18:2n6 with significant decreases in serum 20:4n6 (arachidonic acid) and cutaneous 18:1n9 (oleic acid) and 18:3n3 (alpha-linolenic acid). Dogs in group B had significant increases in serum 18:1n9, 20:3n6 and cutaneous 18:1n9 with decreases in serum 20:4n6, 22:4n6, 22:5n3 and 22:5n6, and cutaneous 18:2n6, 18:3n3 and 20:4n6. There were no significant changes in serum or cutaneous fatty acids for the dogs in group C. This study demonstrates that fatty acid supplements can be used to alter the serum and cutaneous fatty acid compositions of dogs. PMID- 1439207 TI - Comparative behaviour of Brucella abortus strains 19 and RB51 in the pregnant mouse. AB - Pregnant BALB/c mice received various doses of either Brucella abortus strain 19, a smooth vaccine strain, or B abortus strain RB51, a stable rough organism, intraperitoneally on day 9 of gestation to compare the relative pathogenicity of the two attenuated strains. Nine days after inoculation, spleens and placentas were collected for bacteriological and histopathological examination. A dose of 10(7.5) and strain 19 organisms produced a severe necrosuppurative placentitis occasionally accompanied by fetal death. This dose resulted in a 10-fold higher level of splenic infection than did a dose of 10(9.5) strain RB51 organisms, which produced only mild to minimal placentitis not associated with fetal death. Strain 19 infected mice showed seroconversion in the standard tube agglutination test in contrast to the seronegative titre of strain RB51 infected mice. The results of this study corroborate previous investigations on the relative pathogenicity and the serological response of the non-pregnant mouse to strain RB51. PMID- 1439208 TI - In vitro production of specific antibody by equine peripheral blood mononuclear cells using tetanus toxoid as a recall antigen. AB - Anti-tetanus toxoid (TT) antibody (Ig) levels in the supernatant of cultured, pre immunised equine peripheral blood mononuclear cells (PBMC) were measured by an indirect enzyme-linked immunoabsorbent assay (ELISA). Optimal anti-TT Ig production occurred at concentrations of stimulating, purified TT of between 0.001 and 0.1 micrograms ml-1, which varied depending on the cell concentration. Optimal anti-TT Ig production was most consistently produced when the cell concentration was 5 x 10(6) ml-1. At this cell concentration maximal anti-TT Ig was induced using 0.1 micrograms ml-1 TT. At a cell concentration of 5 x 10(6) ml 1 and a TT concentration of 0.1 micrograms ml-1 anti-TT Ig was first detectable in supernatant on day 5 of stimulation. Maximal levels of anti-TT Ig were present in the supernatant by day 10. No anti-TT Ig was produced in cultures of PBMC from non-immune animals. PMID- 1439209 TI - Antipyrine, erythromycin and oxytetracycline disposition in experimental fasciolosis. AB - The effects of fasciolosis on drug disposition were studied by administration of antipyrine, erythromycin and oxytetracycline to sheep and cattle. Fasciolosis was produced by administration of 200 or 400 metacercariae (MC) of Fasciola hepatica to sheep and 500 MC to cattle. The disease was subsequently confirmed by determination of plasma glutamate dehydrogenase and gamma-glutamyl transferase and identification and quantitation of mature flukes in the liver at necropsy. Acute or subacute fasciolosis in sheep was accompanied by a significant decrease in the elimination rate constant (beta) and increase in the elimination half-time (t 1/2) for antipyrine and erythromycin when compared with controls or infected sheep which had been treated with the anthelmintic luxabendazole. An increase in apparent volume of distribution (Vd) was seen only for erythromycin in sheep given 400 MC. There were no changes in the disposition of oxytetracycline in sheep with either acute or subacute infection and no effects on disposition of the three test drugs in chronically infected sheep. With early chronic disease in calves, only the disposition of oxytetracycline was affected; not that of antipyrine or erythromycin. PMID- 1439210 TI - Analysis of complex cytogenetic alterations in three canine mammary sarcomas. AB - Cells of mammary sarcomas in three dogs were analysed cytogenetically. In an osteoidsarcoma, hyperdiploidy with a range of 92 to 98 chromosomes, and several structural aberrations (for example, a derivative chromosome 1, isochromosome 13 and several bi-armed markers) were observed. Isochromosome 13 was also present in a case of an osteoidchondrosarcoma. In a case of chondro-osteosarcoma both hypodiploidy with a chromosome range of 60 to 66 and hyperdiploidy with a range of 115 to 128 and several centric fusions were observed. PMID- 1439211 TI - Pathophysiology of the periparturient egg rise in sheep: a possible role for IgA. AB - The relationship between anti-parasite IgA antibody levels in plasma and the periparturient egg rise in sheep was investigated. Ostertagia circumcincta larvae (5000 third stage larvae three times weekly) were administered to three groups of seven adult immune ewes from 12 weeks before until three weeks after lambing (group 1) or from six (group 2) or 14 (group 3) weeks before until three weeks before lambing. Seven additional ewes were not challenged (group 4 controls). Ewes in groups 1, 2 and 4 received anthelmintics 14 weeks before lambing. Challenge of the pregnant ewes with O circumcincta larvae resulted in substantial increases in faecal egg counts only during the periparturient period regardless of the larval dosing regimen. Furthermore, the periparturient rise in faecal egg counts was closely associated with a significant increase in anti-parasite IgA antibody levels in plasma. This rise in IgA antibody levels occurred at a time when IgA is transported from the gut to milk during early lactation. It is postulated that this may lead to a temporary reduction in abomasal antibody levels of ewes and hence permit the establishment of larvae and, or, the emergence and development of inhibited larvae and thereby lead to the periparturient rise in faecal egg count. PMID- 1439212 TI - Effect of colostrum intake on alpha-lactalbumin concentrations in serum of calves. AB - Seven Friesian calves were fed colostrum for four days beginning within 24 hours of birth, and milk thereafter. The concentration of alpha-lactalbumin in serum was measured by specific radioimmunoassay and compared to IgG assayed by electroimmunodiffusion. Serum concentrations of alpha-lactalbumin peaked at 387 +/- 85 ng ml-1 within eight hours of initial intake of colostrum, declining to 12 +/- 3 ng ml-1 by day 6. IgG rose steadily to 17 mg ml-1 by 48 hours of birth and remained relatively constant thereafter. The temporal pattern of alpha lactalbumin in serum following colostrum intake confirms previous studies suggesting reduced absorption of colostral proteins between 24 and 36 hours. The presence of variable amounts of alpha-lactalbumin in serum even after 17 days, however, indicates limited transfer of milk-derived proteins across the gut at this time. The data further show that cessation of maximal gut transfer does not relate to molecular weight of transferred protein. PMID- 1439213 TI - Tropical theileriosis in Bos taurus and Bos taurus cross Bos indicus calves: response to infection with graded doses of sporozoites of Theileria annulata. AB - This work extends basic knowledge of tropical theileriosis in taurine and crossbred cattle. Infection of Bos taurus and Bos taurus cross Bos indicus (Sahiwal) calves with graded doses of sporozoites of Theileria annulata (Hissar), an Indian stock of the parasite, showed the following to be dose dependent in both cattle types: the time to appearance and population size of macroschizonts, microschizonts and piroplasms, time and severity of pyrexia, anaemia manifested by erythrocyte counts and haematocrit. All infections were accompanied by a prompt and severe panleucopenia. This effect was dose related in both the taurine and the Sahiwal crossbred calves. Lymphocyte counts returned to preinfection levels in the blood of animals which recovered, but death from theileriosis was characteristically accompanied by a persistent and severe lymphocytopenia. Flow cytometry using monoclonal antibodies to bovine mononuclear cells was used to identify the lymphocyte subsets involved in lymphocytopenia. The outcome of infection was dose dependent in the crossbred calves but not in taurine calves. Although the results obtained did not differ qualitatively between the two cattle types, they provided some preliminary evidence for resistance to tropical theileriosis in Sahiwal crossbred calves. PMID- 1439214 TI - Testing meningeal strains of Streptococcus suis to detect M protein genes. AB - Previous reports have suggested that the surface proteins found in meningeal strains of Streptococcus suis might be similar to the M protein of group A streptococci. Fifty-five strains of S suis, including human and swine meningeal and pneumonic isolates, were tested for M protein genes by DNA probes representing the constant domain of the 3' end of the group A, M protein gene. None of the S suis strains examined was positive, indicating that these organisms either lack M protein genes or harbour different genes, not expressing the constant domains of protein M from group A. PMID- 1439215 TI - Effect of wetting a chicken's feathers on the effectiveness of electrical stunning. AB - Chickens were electrically stunned either when their bodies and feathers were wet or when they were dry. The time to recovery of muscular activity following stunning with 81 mA was assessed, and it was found that it was quicker in the wet birds. When hens which had previously been implanted with electroencephalogram electrodes were stunned with 119 mA it was found that the prevalence of somatosensory evoked responses during the first 60 seconds after applying the current was not significantly influenced by the wetness of the birds. It was concluded that electrical stunning with low currents in wet birds leads to a lower prevalence of ventricular fibrillation at stunning and a shorter lasting stun in the non-fibrillated birds. This effect is possibly due to some of the current tracking over the bird's wet body rather than through the brain. PMID- 1439216 TI - Identification of the surface components of Trypanosoma evansi. AB - 125I-labelling was used to characterise the surface components of five stocks of Trypanosoma evansi. Two components of 67 and 60.5 kD were labelled in two of the stocks, a single 60.5 kD component in two other stocks and no components in the remaining stock. These differences are probably related to the labelling method and biochemical differences between the stocks. PMID- 1439217 TI - Quantifying by monoclonal antibodies of specific IgG, IgM and IgA in the serum of minipigs experimentally infected with Actinobacillus pleuropneumoniae. AB - Fifteen minipigs were infected intratracheally with three different doses (10(8), 10(5) or 5 x 10(3) colony forming units) of the reference strains of serotypes 2 or 4 of Actinobacillus pleuropneumoniae, and three remained as controls. The titre of specific IgG, IgM and IgA in the serum was measured weekly for 15 weeks with an indirect ELISA using monoclonal antibodies specific for each isotype. IgG attained the highest titres, IgM lower and IgA the lowest, being only detected in four animals. Serotype 4 evoked significantly higher titres than serotype 2 (P < or = 0.01). In general the highest IgG titres were attained at four to six weeks after infection. Some of the minipigs were reinfected after seven weeks but this evoked an increased titre in only two instances. PMID- 1439218 TI - Erythrocyte protoporphyrin concentrations in clinically normal cats and cats with lead toxicity. AB - Erythrocyte protoporphyrin (EPP) and blood lead concentrations were determined in 91 clinically healthy cats living in the inner suburban area of Sydney, Australia. The mean EPP concentration was 223.4 +/- 186.1 micrograms litre-1 whole blood and the mean blood lead concentration 0.62 +/- 0.25 mumol litre-1. EPP concentrations were also monitored in three cats with confirmed lead toxicity -at the time of diagnosis and one week and one month after chelation therapy with calcium EDTA. EPP concentrations were elevated in two cats and within the normal range in the third cat at the time of diagnosis. EPP concentration were higher in two cats one week after treatment than at the time of diagnosis. One month after chelation therapy, EPP concentrations were normal in two cats but still substantially elevated in the third cat although its blood lead concentration had returned to normal and all clinical signs of lead toxicity had resolved. It was determined that the predominant form of protoporphyrin present in cats with lead toxicity was zinc protoporphyrin. The EPP assay may have limited value in the diagnosis of acute lead toxicity and in monitoring the success of chelation therapy in cats. PMID- 1439219 TI - Pharmacokinetics of carprofen administered intravenously to sheep. AB - Carprofen was administered intravenously to sheep at two dose rates (0.7 and 4.0 mg kg-1), and the pharmacokinetics of the drug studied. Plasma concentrations of the drug were measured by high performance liquid chromatography. Carprofen had a small volume of distribution (Vd[area], 95.5 and 118.4 ml kg-1), a prolonged elimination half-life (t1/2 beta, 26.1 and 33.7 hours) and a slow body clearance rate (Clb, 2.5 ml kg-1 h-1) in sheep. PMID- 1439220 TI - Culture of sheep Chlamydia in a sheep fibroblast cell culture. AB - Abortion and enteric isolates of Chlamydia psittaci from sheep differed in their growth in a fibroblastic cell culture derived from the small intestine of a lamb. Twenty abortion isolates, each from a different farm, produced large inclusions which could be passaged several times whereas 10 enteric isolates each from different farms (but from some of the farms of origin of the abortion isolates) produced sparse inclusions which could not be passaged. This appears to be a rapid method of distinguishing abortion and enteric isolates and may indicate different nutritional requirements or be related to the invasiveness of the isolates. PMID- 1439221 TI - Effect of incomplete immersion of the head in waterbath stunners on the effectiveness of electrical stunning in ducks. AB - Ten ducks were subjected to electrical stunning with their heads completely immersed in the water of a waterbath, and 10 ducks received the same current while only the bill and skin over the crop made contact with the water. The effect on visual evoked responses in the brain was examined. A higher proportion of birds had lost their visual evoked responses immediately following the current with whole head immersion. It is suggested that crop and bill immersion is less effective in disturbing brain function than whole head immersion. PMID- 1439222 TI - Plasma and extracellular volume in calves: comparison between isotopic and 'cold' techniques. AB - While isotopic techniques have largely superseded traditional markers for the determination of the volume of fluid compartments in vivo, they are not always convenient, especially with diarrhoeic animals. A direct comparison was therefore made in week-old calves between Evans blue and radio-iodinated serum albumin as measures of plasma volume and thiocyanate or 24sodium as measures of extracellular fluid space. The correlation coefficients were excellent (1.00, 0.96; P < 0.001) and the calves had plasma and extracellular fluid volumes of 72 +/- 2 and 438 +/- 2 ml kg-1, respectively. The latter value is, though high, typical of young animals and comparable with other data in calves. PMID- 1439223 TI - Diagnosis and prognostic factors in malignant pleural mesothelioma: a retrospective analysis of sixty-five patients. AB - This report is an analysis of the medical records of 83 patients registered between 1960 and 1980 at Helsinki University Central Hospital as having malignant pleural mesothelioma. 65 of 83 patients had histologically confirmed malignant mesothelioma, and are the focus of this analysis. The remaining 18 (22%) patients were excluded because malignant mesothelioma was only confirmed cytologically, or because the primary tumor was not a mesothelioma. The ratio of men to women was 2:1.30 of 65 (46%) patients were not known or not likely to have been exposed to asbestos. The main symptoms at presentation were dyspnea, cough, chest pain, fatigue and weight loss. The median survival from diagnosis was 12 months, and from the onset of symptoms 18 months. Clinical stage and performance status were significant prognostic factors. Hematogenous metastases were present at autopsy in most cases. Disease and performance status therefore need to be well established and documented in clinical trials involving mesothelioma. PMID- 1439224 TI - Structural characterization of the bronchial epithelium of subjects with chronic bronchitis and in asymptomatic smokers. AB - A morphometric study was carried out on biopsy specimens taken from 40 smokers (27 with chronic bronchitis and 13 asymptomatic) submitted to bronchoscopy to identify and quantify the possible structural differences between the two groups. The chronic bronchitic group had a mean age of 65.67 years and 57.04 pack-years of smoking, the asymptomatic group had a mean age of 44.69 years and 22.62 pack years of smoking. 70 biopsy specimens (45 from chronic bronchitics and 25 from asymptomatic smokers), in which large areas of best-preserved and perpendicularly cut epithelium were present, were considered suitable for the study and examined by light and transmission electron microscopy. The mean thickness of surface epithelium (p < 0.001), the number of layers of basal cells (p < 0.001), the intercellular space of the superficial zone of the epithelium (p < 0.05) and the percentage of abnormal bronchial cilia (p < 0.05) were significantly greater in patients with chronic bronchitis than in asymptomatic smokers. No significant difference between the two groups was observed in the thickness of the lamina reticularis of the basement membrane. Goblet cell hyperplasia was more marked in chronic bronchitics than in the asymptomatic smokers (p < 0.001), whereas the frequency of epidermoid metaplasia did not show a significant difference. The morphological study of the bronchial epithelium has allowed the identification of transitional cells, which gives rise to the concept that epidermoid metaplasia may result from conversion of mucous cells. This finding suggests that the different histologic types appearing in lung tumours may originate from one undifferentiated pluripotential stem cell, which is able to differentiate into different histogenetic types. PMID- 1439225 TI - Immediate effects of ethanol on mucociliary clearance in healthy men. AB - A recent experimental study has shown that ethanol concentrations below 1% increase ciliary beat frequency in preparations of sheep trachea. This study was designed to investigate whether low ethanol concentrations also increase mucociliary clearance in man. Mucociliary clearance was measured using inhaled, radiolabelled particles. Clearance was measured in normal men for 30 min under baseline conditions. The subjects then ingested 28 g of ethanol, and clearance was measured for a further 40 min. The subjects reached a mean plasma concentration of 0.04% 30 min after ethanol intake. The mean half-life of the radioactive particles in the lung was 160 min under basal conditions and 257 min after ethanol ingestion. The difference was not statistically significant. We conclude that low ethanol concentrations do not increase mucociliary clearance in man. PMID- 1439226 TI - Comparative assessment of a new breath-actuated inhaler in patients with reversible airways obstruction. AB - Twenty-five patients with reversible airways obstruction inhaled salbutamol (200 micrograms) from the standard press and breathe-metered dose inhaler or a new breath-actuated metered dose inhaler (Aerolin in the Autohaler inhalation device; 3M Health Care Ltd.) in a single dose, double-blind, double-dummy, 2-period, cross-over study. Forced expiratory volume in 1 s, forced vital capacity and peak expiratory flow rate were measured in the 4-hour period after inhalation. The equivalence of the two inhaler devices was determined by analysis of the peak change and time to peak, with reference to the initial recorded baselines of the measured parameters. The efficacy of the two devices was very similar. The breath actuated device is likely to benefit inhaler users who suffer from poor co ordination of actuation and inhalation with a standard inhaler. PMID- 1439227 TI - Nalbuphine analgesia preserves ventilation after thoracotomy despite a reduction in inspiratory drive. AB - The respiratory effects of analgesia with nalbuphine were studied in 9 patients after thoracotomy. The pain score was measured by a visual analogue scale. Ventilatory pattern and occlusion pressure (P0.1) were studied during spontaneous breathing and during CO2 rebreathing, before and 0.5, 1, 2.5, 3.5 and 6 h after a 0.3-mg.kg-1 dose of intravenous nalbuphine. Compared to baseline values obtained before the injection, nalbuphine produced a decrease in the pain score (p < 0.001) during the 6-hour experiment period. In spontaneous breathing, P.01 was reduced by 15% in 1 h and remained decreased during 3.5 h (p < 0.05), whilst PaCO2 and ventilation (VE) remained unchanged. The P0.1 responsiveness to CO2 was decreased from 0.5 to 2.5 h after the nalbuphine injection (p < 0.05), but the VE responsiveness to CO2 was reduced only after 1 h (p < 0.01). This study shows that, while post-thoracotomy pain was reduced by analgesia, neuromuscular inspiratory drive and chemosensitivity to CO2 were weakened, without any change in spontaneous ventilation. A partial improvement in the thoracopulmonary mechanics induced by the reduction in chest pain could explain the maintenance of ventilatory level in spite of a decreased neuromuscular inspiratory drive. PMID- 1439228 TI - Changes of circulating atrial natriuretic peptide and antidiuretic hormone in obstructive sleep apnea syndrome. AB - Patients with obstructive sleep apnea (OSA) syndrome are known to exhibit nocturnal natriuresis/diuresis. We studied plasma and urinary levels of atrial natriuretic peptide (ANP), a potent natriuretic hormone released from the heart, and plasma antidiuretic hormone (ADH) levels in patients with OSA during awake and sleeping periods, to compare with those of normal subjects. Seven patients with OSA and 6 normal subjects were studied. Arterial blood samples were drawn during the awake and the sleeping period, while in patients with OSA, blood samples were obtained during the apneic period. Urine samples were collected over two 12-hour periods (9 a.m.-9 p.m. and 9 p.m.-9 a.m.) In patients with OSA, plasma ANP as well as urinary ANP excretion increased during the apneic period compared with the awake period. There was a significant negative correlation between plasma levels of ANP and ADH in patients with OSA. On the other hand, normal subjects had no apparent differences in plasma and urinary ANP levels between the two periods. It is suggested that nocturnal increase in ANP and decrease in ADH are responsible for the nocturnal diuresis and natriuresis associated with OSA. PMID- 1439229 TI - Associations between atopy, asthma history, respiratory function and non-specific bronchial hyperresponsiveness in unselected young asthmatics. AB - We evaluated the relationship between bronchial hyperresponsiveness and atopic status, clinical symptoms and airway calibre in a group of Italian conscripts who reported having bronchial asthma. 126 subjects were studied. Bronchial responsiveness was measured by the methacholine test, and atopic status was assessed by skin tests. A measurable PC20 was detected in 106 subjects. On the basis of the methacholine threshold concentration the sample was divided into four categories. Subjects with a low threshold response had an earlier onset of the disease and tended to take more drugs. The four categories also differed in lung function and skin reactivity towards Dermatophagoides pteronyssinus whereas no difference was found in skin reactivity towards grasses or the overall panel of tested allergen extracts. In conclusion, we found that bronchial hyperresponsiveness is related to both clinical history and lung function, whereas the relationship with atopic status seems to be allergen specific. PMID- 1439230 TI - Massive bilateral pleural effusion as the only first presentation of systemic lupus erythematosus. AB - A rare case of systemic lupus erythematosus (SLE), with massive bilateral pleural effusions as the first manifestation, is described. The patient was a previously healthy 20-year-old soldier. Initial investigations were unrevealing, but after 3 months the patient developed the full-blown syndrome. He responded well to corticosteroids and cyclophosphamide with resolution of the pleural effusions and improvement of the clinical picture. SLE should always be considered in cases of massive pleural effusions, even in the absence of other overt stigmata of the disease. PMID- 1439231 TI - Obstruction of upper airways complicating tracheostomy and use of neodymium Yag laser. AB - Mucoid impaction of tracheobronchial tree is a common condition which may complicate tracheostomy. Here we describe a case of a 72-year-old man, status after tracheostomy, who presented to the hospital with an acute upper airways obstruction and respiratory arrest due to a tracheal cast. The cast was successfully dislodged by the Nd-Yag laser. PMID- 1439232 TI - Pulmonary capillary hemangiomatosis: report of a case and review of the literature. AB - We describe a case of pulmonary capillary hemangiomatosis in a 60-year-old woman with a 1-year history of progressive exertional dyspnea. Four years before admission a diagnosis of breast cancer was made, and she underwent mastectomy plus radiation therapy and treatment with oral antiestrogens. The chest X-ray showed bilateral interstitial infiltrates. Pulmonary function studies revealed a severe restrictive pattern. Abundant red blood cells were found in the bronchoalveolar lavage fluid. On the basis of open lung biopsy, interstitial fibrosis was diagnosed. Cardiac catheterization revealed pulmonary hypertension. Steroids were prescribed, but the patient's condition continued to deteriorate and she died approximately 3 years after presentation. The identification of proliferating and invasive capillaries, which are unique to pulmonary capillary hemangiomatosis, led to the correct diagnosis at autopsy. PMID- 1439233 TI - Mediastinal fibrosis and radiofrequency radiation exposure: is there an association? AB - A 45-year-old officer, working for a period of 18 years at a military radar base, presented with progressive exertional dyspnea, dry cough, and hemoptysis. Subsequent evaluation demonstrated a left pulmonary artery occlusion as well as a left upper lobe bronchus stenosis, due to a dense fibrotic mediastinal mass. Histologically, this proved to be idiopathic mediastinal fibrosis (IMF). The development of IMF in a man exposed for a long period to radio-frequency radiation (RFR) is unique in the literature in English. The possible association of radiation exposure with IMF is discussed. PMID- 1439234 TI - A localized pleuropulmonary lesion induced by long-term therapy with amiodarone. AB - Pulmonary toxicity is an important adverse effect of amiodarone therapy that usually manifests as an acute or chronic diffuse lung disease; in rare cases localized lesions have also been described. We observed a solitary mass localized in the left lung base and involving the adjacent pleura in a 69-year-old man who had been treated for 1 year with amiodarone (cumulative dose 52 g). Cytological and histological examination showed that the lesion consisted of fibrotic tissue and a massive macrophagic infiltration. Following suspension of amiodarone and surgical excision, there was a complete recovery and the mass did not relapse. We confirm that respiratory complaints can occur in patients treated by long-term amiodarone therapy and that lung involvement can manifest with a solitary localized (fibrotic) lesion. PMID- 1439235 TI - Influence of OM-85 BV on different humoral and cellular immune defense mechanisms of the respiratory tract. AB - To clarify the mode of action of an oral bacterial extract (OM-85 BV) on local airway immunity pre- and posttherapeutic washings from bronchoalveolar lavage (BAL) fluid of 28 adult patients with nonobstructive chronic bronchitis were analysed. In comparison to healthy controls, an elevation of total cell count due to an increased number of PMN leukocytes, and an impaired activity of the alveolar macrophages measured by the chemiluminescence response to opsonized zymosan was observed in patients with chronic bronchitis. After treatment with OM 85 BV, the BAL CD4+/CD8+ lymphocyte ratio and BAL interferon-gamma levels were increased. The alveolar macrophage activity was normalized and the BAL IgA was regulated from a reduced or hyperelevated to a moderately increased level. PMID- 1439236 TI - Adhesion molecules in antibacterial defenses: effects of bacterial extracts. AB - Adhesion of polymorphonuclear leukocytes (PMN) to vascular endothelium is one of the first events in their response against local bacterial infection. Different adhesion molecules sequentially mediate PMN adherence to endothelium and extravasation into inflamed tissues. We show that bacterial extracts OM-85 BV and OM-89 increase the expression of adhesion molecules at the surface of PMN and we suggest that this upregulation could be linked to the beneficial effect of bacterial extracts in the prevention of respiratory tract infections. PMID- 1439237 TI - Clinical experience with OM-85 BV in upper and lower respiratory tract infections. AB - The preventive effect of OM-85 BV on recurrent ENT and respiratory tract infections has been documented in a series of clinical trials. This article reviews the more significant controlled clinical trials investigating the efficacy and safety of OM-85 BV in airway infections. The literature reviewed covers all age groups. In summary, the administration of OM-85 BV was associated with a decrease in the number of acute exacerbations, with an increase in the number of patients remaining free from infections and with a decrease in antibiotic consumption. These results indicate the efficacy of oral immunostimulation with the bacterial extract OM-85 BV in all age groups and demonstrate its protective effect against recurrent airway infections. PMID- 1439238 TI - Mucosal immunology of the upper respiratory tract. AB - The palatine tonsils and nasopharyngeal adenoids represent the predominant immunocompetent tissue of the upper respiratory tract. Its major function is as a first line of defense against viral, bacterial, and food antigens that enter the upper aerodigestive system. Another major function of the tonsils and adenoids is to supply the local mucosal immune system of the upper respiratory tract with dimeric IgA-producing B cells. Secretory IgA has particular hydrophilic properties and is capable of preventing adsorption and penetration of bacteria and/or viruses into the upper respiratory tract mucosa. In addition, the role of the indigenous flora of the upper respiratory tract, particularly the viridans streptococci has been emphasized as providing a valuable source of bacterial interference to the colonization of potential pathogens. PMID- 1439239 TI - Familial occurrence of combined pigment epithelial and retinal hamartomas associated with neurofibromatosis 2. AB - Combined pigment epithelial and retinal hamartomas are rare lesions that usually occur sporadically in individuals without systemic abnormalities. However, they have been reported in isolated patients with neurofibromatosis 1 and 2. No familial cases have been reported. The cases of four patients with unilateral macular lesions from three consecutive generations of a single family are presented: two of the patients also have neurofibromatosis 2. The ophthalmoscopic appearance of their ocular lesions resembles combined pigment epithelial and retinal hamartomas. The morphologic differences in the lesions of these 4 patients, whose ages are 8 months, 5 years, 29 years, and 65 years, may serve to demonstrate the evolution of this type of hamartoma. PMID- 1439240 TI - Subretinal neovascularization secondary to choroidal septic metastasis from acute bacterial endocarditis. AB - The clinical features of an infective embolic choroidopathy are described, from its early onset to late complications in a 45-year-old man with acute Staphylococcus aureus endocarditis of the aortic valve. Initial fundus examination revealed, in addition to fresh choroidal lesions, stigmata of a previous embolic episode secondary to endocarditis from Actinobacillus actinomycetemcomitans. The choroidal lesions were extremely asymmetrical, with a clear preference for localization in the left eye. Similar ocular findings were seen in a 78-year-old female with mitral valve prolapse and acute S. aureus endocarditis. In this case, however, choroidal involvement from septic emboli spread was bilateral and roughly symmetrical. Choroidal neovascular membranes arising in scars from choroidal septic emboli occurred in the macular area of the left eye of both patients, 10 months and 5 years after embolization, respectively. PMID- 1439241 TI - The frequency of subretinal fluid drainage and the reattachment rate in retinal detachment surgery. AB - The reattachment rate and the frequency of subretinal fluid drainage were reviewed in 771 eyes with rhegmatogenous retinal detachment that had undergone transscleral retinal detachment surgery between January, 1980 and December, 1989. During this period, the frequency of drainage decreased from 63.6% in 1980 to 14.1% in 1989. This decrease has not been accompanied by any change in the reattachment rate. The difference between visual acuity in eyes that underwent the operation when drainage was performed in only certain selected cases and visual acuity in eyes operated on when drainage was performed more frequently was not statistically significant (P = 0.966). It is suggested that the decrease in the frequency of drainage was due to a carefully followed method of patient management, including preoperative bed rest, use of criteria to establish nondrainage operation, use of transilluminator, and control of intraocular pressure. PMID- 1439242 TI - Digital overlay of fluorescein angiograms and fundus images for treatment of subretinal neovascularization. AB - A system for comparing sequential fundus photographs and angiograms has been developed using a personal computer and commercially available image processing software. This process provides rapid results and a high degree of accuracy in image correlation, even when images come from different cameras with different magnifications. Though no concentrated effort was made to compare the superiority of this method to the manual technique, the value of the manual results is fully acknowledged, and this technique is offered as another method of achieving the same end. This technique can be used to determine the adequacy of treatment of subretinal neovascularization, recurrence of subretinal neovascularization in subsequent angiograms, pigment epithelial creep, and changes in fundus lesions. PMID- 1439243 TI - Pathologic findings in pathologic myopia. AB - A retrospective study was conducted of 308 eyes with pathologic myopia obtained from 202 patients (23 surgical eyes; 285 post mortem eyes) over a 67-year period. Histopathologic findings and percentage of eyes affected, in decreasing order of frequency, were myopic configuration of the optic nerve head, 37.7%; posterior staphyloma, 35.4%; degenerative changes of the vitreous, 35.1%; cobblestone degeneration, 14.3%; myopic degeneration of the retina, 11.4%; retinal detachment, 11.4%; retinal pits, holes, or tears, 8.1%; subretinal neovascularization, 5.2%; lattice degeneration, 4.9%; Fuchs spot, 3.2%; and lacquer cracks, 0.6%. The reasons for enucleation in the surgically obtained eyes included, in decreasing order of frequency: degeneration after retinal detachment; secondary glaucoma; endophthalmitis; postsurgical epithelial ingrowth; expulsive hemorrhage; degeneration after cataract extraction; and presumed intraocular tumor. Clinicopathologic correlations are discussed. PMID- 1439244 TI - Experimental studies of the combined use of vitreous substitutes of high and low specific gravity. AB - The combined use of high and low specific gravity liquid vitreous substitutes has been studied in the rabbit. Eyes having undergone 1) vitreous replacement with silicone liquid combined with a perfluoropolyether liquid of high viscosity; 2) replacement with the perfluoropolyether or silicone alone; or 3) vitrectomy only (control) were compared under conditions of a cell-injection model of traction retinal detachment. Some of the control eyes (3 out of 9) and silicone-filled eyes (2 out of 10) developed total retinal detachments involving all quadrants; in the silicone-filled eyes the detachments extended behind the silicone globule. Conversely, in the eyes undergoing replacement with the two liquids or with the perfluoropolyether liquid alone, retinal detachments never extended to the inferior quadrants underlying the perfluoropolyether globule. In other experiments, the tendency toward emulsification of a low-viscosity perfluorocarbon liquid was reduced when it was used in combination with silicone liquid, in comparison to when this liquid was used alone. PMID- 1439245 TI - A new magnifying indirect stereo ophthalmoscope. AB - A new magnifying indirect stereo ophthalmoscope had been designed, built, and tested. Magnification is achieved by means of Keplerian telescopic systems mounted in each eyepiece. Schmidt or Pechan prisms are incorporated to shorten the length of the telescopic systems. Using a +20 diopter condensing lens, the total retinal magnification achieved with this system varies from 5.6x at a 40-cm observation distance to the aerial image to 9.4x at a 25-cm observation distance. When the fundus is viewed through a dilated pupil extraordinary stereopsis is obtained. When combined with the magnification, this stereopsis greatly enhances the view of the posterior segment of the eye. PMID- 1439246 TI - Peripapillary subretinal neovascularization. A review. AB - Peripapillary choroidal neovascularization is an important feature in the pathogenesis and treatment of a number of disorders affecting the optic nervehead and adjacent chorioretinal areas. Although less well understood than its macular counterpart, peripapillary subretinal neovascularization possesses characteristic clinical and histopathologic features that directly affect its prognosis and management. This review provides a summary of the diseases in which peripapillary subretinal neovascularization occurs and an overview of studies on the natural history, clinicopathologic findings, and therapy. In addition, a pathogenetic model of peripapillary subretinal neovascularization is discussed based on these findings. PMID- 1439247 TI - A method for induction of posterior vitreous detachment during vitrectomy. AB - Complete surgical removal of the posterior vitreous requires the presence of a posterior vitreous separation from the retina. Although a partial or complete posterior vitreous detachment is usually present before surgery, occasionally this separation must be induced during the course of a pars plana vitrectomy. A simple method for creation of a posterior vitreous detachment during surgery is described. This alternative technique seems to be an efficient and safe method for achieving this important surgical objective. PMID- 1439248 TI - Viewing fluorescein angiograms with stereopsis significantly assists interpretation. PMID- 1439249 TI - Arnall Patz Medal for Excellence in Retinal Vascular Disease. Matthew D. Davis, MD. PMID- 1439250 TI - Laser treatment of eccentric leaks in central serous chorioretinopathy resulting in disappearance of untreated juxtafoveal leaks. AB - In central serous chorioretinopathy (CSCR) laser treatment of leaking points close to the macular center should be avoided because of the possibility of producing juxtafoveal scotoma and stimulating choroidal neovascularization. Nine eyes of nine consecutive patients with CSCR had two or more leaking points within a macular detachment, one of which was foveal or near to the fovea. Photocoagulation with green argon laser was performed in all eyes, treating all the leaking points except for the central one. Visual symptoms regressed after treatment, and the serous detachment was resolved 10 days to 4 weeks after photocoagulation in all cases. Fluorescein angiography showed no leakage at either the central leakage point or the leakage point that had been treated. These results led us to believe that the central or dependent leak in our cases was not sufficient to maintain the serous detachment by itself. An alternative hypothesis is that the untreated leak did not represent real fluid movement but only diffusion of fluorescein molecules, or a false leak. In cases of CSCR with multiple leaks within a single macular detachment, we believe that a foveal leak may be a dependent or false leak and that direct treatment is not necessary. PMID- 1439251 TI - [A case of aconitine poisoning accompanied by bidirectional ventricular tachycardia treated with lidocaine]. AB - A rare case of aconitine poisoning accompanied by bidirectional ventricular tachycardia was reported. A 67-year-old male ate several leaves of a wild plant which had been collected in Fukushima Prefecture, Japan. About 90 minutes later, he felt numbness and weakness of the limbs and vomiting took place, and he was admitted to our hospital. The blood pressure was 80/60mmHg, and the electrocardiogram showed multiple premature ventricular contractions and bidirectional ventricular tachycardia. After bolus injection of lidocaine, continuous administration of the drug was started. Immediately after starting the treatment, the arrhythmia disappeared and hemodynamic changes improved. Thereafter the wild plant was ascertained to be a species of Aconitium. Diagnosis of aconitine poisoning was made. According to the fact that aconitine acts as a agonist of Na-channel receptor, antiarrhythmic agents which belong to Vaughan Williams' classification I might be the first choice for the therapy of aconitine induced arrhythmias. PMID- 1439252 TI - [A case of painless myocardial injury probably caused by coronary artery spasm]. AB - A 53-year-old male was admitted to the hospital due to electrocardiographic ST segment elevation in V1-4 with ST-segment depression in the inferior leads, which suggested acute myocardial infarction. He had a cough and a slight fever without chest pain. Serum creatine kinase and its myocardial band were slightly elevated but creatine kinase value did not exceed twice the normal upper limit. Emergent coronary arteriography (CAG) revealed intact coronary arteries. The CAG in a chronic stage again revealed intact coronary arteries. Intracoronary administration of acetylcholine of 100 micrograms to the left coronary artery and 50 micrograms to the right coronary artery provoked diffuse spasm in the right and left coronary arteries. The electrocardiogram (ECG) during the right coronary artery spasm revealed ST-segment depression in the inferior leads with ST-segment elevation in V2 and V3, which resembled the ECG finding at the time of the patient's admission. With intracoronary isosorbide dinitrate, the spasm and ST segment elevation were resolved. These findings strongly suggest that coronary spasm can cause myocardial injury indicated by a slight elevation of serum creatine kinase value. PMID- 1439253 TI - [False aneurysm formation during the chronic phase of myocardial infarction at the margin of a previously-detected true aneurysm]. AB - The patient was a 59-year-old man who had acute extensive anterior myocardial infarction in October, 1989. One month later, he was transferred to Kyoto University Hospital and underwent cardiac catheterization. Left ventricular aneurysm and significant stenosis in the proximal portion of the left anterior descending artery were documented. Because he experienced chest pain on slight exertion accompanied by a slight increase in the depth of the negative T wave on electrocardiogram, percutaneous transluminal coronary angioplasty (PTCA) was performed. Thereafter, chest pain disappeared, and the patient was discharged. Three months later, he was re-admitted to Kyoto University Hospital for a repeat cardiac catheterization after PTCA. PTCA site was found to be restenosed, and a small diverticulous aneurysm was found at the margin of the previously-detected ventricular aneurysm. As the diverticulous aneurysm was considered likely to precipitate the ventricular aneurysm into rupture, expeditious left ventricular aneurysmectomy was performed to prevent cardiac rupture. Ventricular aneurysms, common complications in myocardial infarction, are of two types, either true or false. Most aneurysms develop during the acute phase of myocardial infarction, and rupture of true aneurysms during the chronic phase of myocardial infarction rarely occurs. However, in the present case, a small diverticulous aneurysm, which was not demonstrated at the initial cardiac catheterization, developed during the chronic phase of myocardial infarction. Pathological examination revealed that the diverticulous aneurysm was a false aneurysm due to incomplete rupture. When the common pathogenesis of ventricular aneurysms in myocardial infarction is considered, the present report might represent an extraordinary rare case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439254 TI - [A case of myxedema heart with serial endomyocardial biopsy]. AB - We report a case of middle-aged woman with myxedema heart who presented congestive heart failure due to myocardial damage caused by myxedema, and showed reversible and irreversible myocardial change proven by serial endomyocardial biopsy. She was admitted to our hospital because of facial, peripheral edema and dyspnea. On admission, chest X-P revealed severe cardiomegaly (CTR 70%) and bilateral pleural effusion. Electrocardiogram showed low voltage. Echocardiogram and chest CT revealed a large amount of pericardial effusion. No significant stenosis was observed on a coronary arteriogram. Laboratory data showed elevated TC, CPK, LDH values and immunological test indicated high titer of thyroid test and microsome test. Thyroid function test revealed primary hypothyroidism with low T3, low T4 and high TSH levels. Replacement therapy for hypothyroidism in addition to digitalis and diuretics++ has been started. Seven months after initial evaluation, this therapy has resulted in dramatic clinical improvement. Transvenous right ventricular endomyocardial biopsy demonstrated vacuolated degeneration on admission and improvement of vacuolated degeneration with a slight degree of fibrosis after therapy. This pathological finding suggests that myxedema heart is able to produce both reversible and irreversible myocardial damage. PMID- 1439255 TI - [A case of adult pulmonary supravalvular membranous stenosis which was successfully treated by percutaneous transluminal balloon dilatation]. AB - We report a case of adult pulmonary supravalvular stenosis which was successfully treated with percutaneous transluminal balloon dilatation (PTBD). A 42-year-old man was admitted for a heart murmur and abnormal findings in the screening chest roentgenogram. Having no symptoms on admission, his physical activity was evaluated as Class I according to the classification of the New York Heart Association. A systolic murmur (Levine III/VI) with split second sound was audible at the left sternal border in the 3rd intercostal space. Chest roentgenogram revealed 57% of the cardio-thoracic ratio and no signs of increased pulmonary vascular markings. ECG showed incomplete right bundle branch block. Echocardiography and right ventriculography visualized the supravalvular membranous structured stenosed pulmonary artery 1cm above the pulmonic valve. Systolic pressure gradient between the right ventricle and the distal main pulmonary trunk was 54mmHg. The patient was diagnosed as having pulmonary supravalvular membranous stenosis. PTBD was applied using Inoue balloon catheter, where inflation was initiated from approximately 120% of pulmonary arterial diameter and terminated at 150%. This procedure decreased systolic pressure gradient from 54mmHg to 36mmHg without complication. After PTBD right ventriculography demonstrated that a part of the membranous structure had become floppy and movable. Pulmonary arterial diameter was unchanged. We considered that PTBD tore the membranous structure, which consequently resulted in the decrease of systolic pressure gradient. Systolic murmur diminished to Levine II/VI. Six months later, cardiac catheterization showed no change in systolic pressure gradient compared with that immediately after PTBD. This is the first report on pulmonary supravalvular membranous stenosis successfully treated with PTBD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439256 TI - [A case of rectus sheath hematoma]. AB - The following is a rare case of rectus sheath hematoma. The patient was a 78-year old man with a past history of axillo-femoral bypass operation. He contracted a cold, and when he coughed severely, acute lower abdominal pain occurred. Abdominal echography and CT scanning confirmed the presence of a hematoma in the rectus abdominis muscle. Before, patient was diagnosed as acute abdomen and surgery was performed. Recently, accurate diagnosis has been made easily by echography or CT. PMID- 1439257 TI - [A case of nonobstructive hypertrophic cardiomyopathy associated with ventricular tachycardia and sick sinus syndrome]. AB - We examined, a 64 year old man with hypertrophic nonobstructive cardiomyopathy (HNCM) accompanied with dizziness. Twenty-four hour ECG monitoring showed sinus bradycardia and sinoatrial block. Electrophysiologic study demonstrated inducible sustained ventricular tachycardia (VT) by continuous rapid high right atrum pacing during which systolic blood pressure fell to 40 mmHg. Induced VT degenerated into ventricular fibrillation in ten seconds. We implanted a DDD pacemaker for sick sinus syndrome (SSS) and administrated 90mg/day of diltiazem for VT. Treadmill exercise test was carried out while the patient was taking diltiazem and no arrhythmia was induced. This case of HNCM is rare in that he presented both sick sinus syndrome and sustained VT. PMID- 1439258 TI - [The clinical significance and degradation of basement membrane in lung cancer]. PMID- 1439259 TI - [Respiratory and arousal responses during sleep: an experimental study in sleeping dogs]. PMID- 1439260 TI - [Retrograde perfusion]. PMID- 1439261 TI - [Regional blood flow measurement with nonradioactive microspheres]. PMID- 1439262 TI - [Laryngeal mask airway: application to emergency and intensive care]. PMID- 1439263 TI - [Heart diseases in the elderly (3)--Cardiac function and heart failure in the elderly]. PMID- 1439264 TI - [An experimental study of determining the appropriate frequency of radiofrequency catheter ablation in vitro and in vivo for ventricular tachycardias]. AB - The purpose of this study was to examine the appropriate frequency of radiofrequency catheter ablation (RFA) for ventricular tachycardia. Radiofrequency energy generated by a device in which the frequency could be changed, was delivered from an electrode catheter with an electrode tip-width of 4 mm. RFA was performed for 10 seconds with 20W (50V x 0.4A) using 7 different frequencies from 10 to 500 kHz on ventricular myocardium in vitro and in anesthetized dogs. The ablated lesion was significantly larger with RFA of 200 300 kHz in both surface area and depth (p less than 0.05). The appearance of ventricular arrhythmia during RFA increased as the frequency decreased, and one dog applied with RFA of 100 kHz had spontaneous ventricular fibrillation resulting in death. All dogs with frequency less than 100 kHz had a muscle cramp during RFA. We conclude that appropriate frequency seems to be 200-300 kHz to obtain a large ablated lesion, and a frequency higher than 300 kHz seems suitable to avoid arrhythmia. We also conclude that a frequency under 100 kHz should not be used. PMID- 1439265 TI - [Postural changes in finger and toe pulse waves]. AB - Finger and toe pulse waves were simultaneously recorded in medical students and outpatient hypertensive patients. The delay of the rise of toe pulse to that of finger pulse (t) was almost halved in students on postural change from the supine position to the sitting position. This was mainly due to an increase in the pulse wave velocity in the aorta, which was thought to be induced by the increase in hydrostatic pressure in the aorta. In students a marked dicrotic wave was observed in both finger and toe pulse waves. That the interval between the main and dicrotic waves (T) was shorter for finger pulse than toe pulse also seems to be ascribable to the influence of the intraaortic pressure: Pulse was transmitted faster in the systolic phase than in the diastolic phase. The features of pulse waves of hypertensive patients were that (t) was short even in the supine position, and that dicrotic wave was small or absent especially for toe pulse. These differences were considered to be accounted for by the high blood pressure and the structural change of arterial wall in the hypertensive patients. PMID- 1439266 TI - [Myocardial infarct size and left ventricular function in diabetic patients]. AB - We determined the relationship between myocardial infarct size (MIS) estimated by electrocardiographic measurements of infarct size (QRS score) and left ventricular function estimated by angiographically left ventricular ejection fraction (EF). MIS estimated by QRS score were the same in both DM and NDM (5.2 +/- 0.5 vs 4.3 +/- 0.4: p greater than 0.05), but EF in DM was significantly lower than in NDM (43.1 +/- 1.4 vs 51. +/- 1.1%: p less than 0.05). There was clear linear correlation between MIS and EF in NDM (r = -0.71) but not in DM. EF was much lower in DM than in NDM even at the same QRS score level. There were no differences in blood pressure, serum lipid levels, age, and the site of the myocardial infarction. The most likely explanation for this appears to be due to a previous left ventricular disease in DM. PMID- 1439267 TI - [Abnormalities in the signal-averaged electrocardiogram in Ebstein's anomaly]. AB - Abnormalities in the signal-averaged electrocardiogram (SAECG) of patients with Ebstein's anomaly were studied. A SAECG was obtained in 4 patients with Ebstein's anomaly, aged 3 to 25 years. The control groups included 8 patients with atrial septal defect (ASD group), 10 with right bundle branch block (RBBB group), 8 with Wolff-Parkinson-White (WPW) syndrome (WPW group), and 40 normal subjects (Normal group). The SAECG was calculated by the vector-magnitude method using the VCM 3000. The root-mean-square during the initial 20 msec of the filtered QRS (i-RMS) was very small in 2 older patients with Ebstein's anomaly compared to the ASD group, the RBBB group and the Normal group, and was as small as that in the WPW group. This probably was affected by the delta wave associated with Ebstein's anomaly or concealed accessory pathway. The root-mean-square during the terminal 40 msec of the filtered QRS (t-RMS) was small in the patients with Ebstein's anomaly and the RBBB group. Two patients with Ebstein's anomaly had a smaller t RMS than the RBBB group, suggesting pathological changes of an atrialized right ventricle. In conclusion, SAECG is useful for evaluating patients with Ebstein's anomaly, especially older patients. PMID- 1439268 TI - [Effects of Nd:YAG laser irradiation on ventricular myocardium in dogs using an artificial sapphire tip contact laser catheter]. AB - To apply Nd:YAG laser irradiation through a new sapphire tip contact laser method to catheter ablation in treatment of tachy-arrhythmias, effects of laser irradiation on ventricular myocardium were investigated in 10 mongrel dogs. Nd:YAG lase (1064nm) discharges were delivered to different sites on the endomyocardium at power of 5, 10, 15, 20 or 25w with duration of 3, 5, or 10 seconds (sec.) respectively in closed beating hearts. Histopathologically, the lesion irradiated was clearly demarcated from the normal myocardium by the construction band necrosis zone. The depth of injured myocardium was less than 2mm with 3 sec. irradiations, with 5 sec. from 1 mm to 4 mm in proportion to power increase, with 10 sec. from 3mm to 8 mm in proportion to the power from 5w to 15w and could not be measured in cases of more than 20w irradiations. Although with every irradiation duration, the depth of injury increased in proportion to the power increase. With the same total energy, a longer time of irradiation produced deeper injury than a shorter time. This method makes it easier to keep the laser positioned to target than bare laser, and is suitable for use in catheter ablation. PMID- 1439269 TI - [Endothelium-derived contracting and relaxing factors]. PMID- 1439270 TI - [Endothelial cells and atherosclerosis]. PMID- 1439271 TI - [Haemodynamic effects of intravenous isosorbide dinitrate in congestive heart failure]. AB - The effects of intravenous infusion of isosorbide dinitrate (ISDN) were evaluated in 22 patients with congestive heart failure. These patients did not receive vasodilator therapy before this study. Seven of these patients (two bolus groups of 5.0 mg and 7.5 mg each) were infused bolusly. The mean PA, PCWP and mean RA decreased for 5 min and, after 60 min, they were back to the original levels. The mean Ao had an accentuated change when the 7.5 mg bolus was injected, but, apart from that, changes were minimal. The CI changed little and upwardly. ISDN was infused continuously in 10 patients (two infusion groups of 5.0 mg/hr and 7.5 mg/hr each) whose mean PA, PCWP and mean RA decreased for 15 min and continued downwardly but mildly for 120 min. The mean Ao did not change much and the CI slightly increased. Five of the 22 patients (bolus+infusion group of 5.0 mg and 5.0 mg/hr) showed rapid response but the parameters only slightly changed. Since this group included severe heart failure patients, the results observed were milder. The response of all 5 groups receiving ISDN infusion were confirmed by the serum ISDN concentration curve. These results indicate that continuous infusions of 7.5 mg/hr ISDN or bolus infusions of 5.0 mg and infusion of 5.0 mg/hr improved haemodynamics in patients with congestive heart failure. PMID- 1439272 TI - [Cardiac performance in total anomalous pulmonary venous connection]. AB - Cardiac performance in 54 patients with total anomalous pulmonary venous connection was investigated by cardiac catheterization before and after surgery. 51 patients underwent intracardiac repair, and 17 of them died during or immediately after operation. According to the preoperative study, the left ventricular ejection fraction (LVEF) of surviving patients was significantly higher than that of patients who died, and the pulmonary arterial mean pressure of surviving patients was significantly lower than that of patients who died. However, there was no significant difference between the left ventricular end diastolic volume (LVEDV), right ventricular ejection fraction (RVEF), and right ventricular end-diastolic volume (RVEDV) in surviving patients and those who died. Post-operative catheterization studies showed significant increases of LVEF and LVEDV compared to pre-operative figures. RVEF and RVEDV and pulmonary arterial mean pressure decreased significantly after surgery. It was concluded that preoperative cardiac performance of surviving patients was better than that of those who died, and post-operative cardiac performance of surviving patients was basically normal. PMID- 1439273 TI - [Electrophysiologic effects of flecainide on guinea pig atrium]. AB - We investigated the effects of flecainide on guinea pig atrial muscle. Using Langendorff's method, the whole heart of a guinea pig was perfused with Tyrode's solution containing acetylcholine (3 x 10(-7) M). Then, with right atrial extrastimulus and high frequency pacing method, the following values were measured before and after administration of flecainide (10(-7)-10(-5) M). A) Effective refractory period (ERP); the longest coupling interval which failed to produce right atrial activity at premature stimulus. B) Interatrial conduction time (ACT); After right atrial stimuli by trains at PCL 200 ms for 5 min the interval from the stimulation to the first deflection of the left atrial activity. C) Atrial fibrillation threshold (AFT); the minimal amount of current required to induce atrial fibrillation lasting for more than 30 sec by 50 Hz high frequency stimulation. Flecainide lengthened ERP (> or = 3 x 10(-5) M) and ACT (> or = 10(-7) M). Flecainide (10(-5) M) significantly increased AFT which correlated well with ERP (r = 0.81, p < 0.002) and ACT (r = 0.84, p < 0.002). In conclusion these effects of flecainide on guinea pig atrium might explain in part the clinical effectiveness of the drug on paroxysmal atrial fibrillation. PMID- 1439274 TI - [Prophylactic use of antibiotics for fever following fiberoptic bronchoscopy and bronchography]. AB - To evaluate the effect of bacampicillin hydrochloride on fever following fiberoptic bronchoscopy and bronchography, we conducted multi-institutional randomized study. In bronchographic examinations, the rise of body temperatures in the bacampicillin group (0.82 +/- 0.13 degrees C: mean +/- SE) was significantly smaller than that in the control group (1.39 +/- 0.25 degrees C) on the second day of examination. Bacterial infection may contribute to the rise of temperature on the day following bronchography, but no pneumonia or sepsis was observed. There was no differences in the rise of body temperature on the first, third or fourth day. In fiberoptic bronchoscopic examinations, there was no difference between the two groups. We conclude that there is no clinical indication of the value of prophylactic use of antibiotics in either fiberoptic bronchoscopy or bronchography. PMID- 1439275 TI - [The acute and chronic effects of bunazosin on exercise capacity estimated by the anaerobic threshold in patients with chronic congestive heart failure]. AB - To study the effect of bunazosin on exercise capacity in patients with congestive heart failure (NYHA II-III), anaerobic thresholds (AT, VO2, ml/min/kg) were measured before (control) and after initial 1 = 2mg administration of bunazosin (acute phase; N = 14) and after two weeks of bunazosin therapy (3mg/day, 1mg t. i. d., chronic phase; N = 6). AT were determined by Wasserman's V-slope method during ergometer exercise test with a ramp loading (10 watt/min). AT increased significantly from control during both acute (14.2 +/- 2.7 to 16.9 +/- 3.6 ml/min/kg p < 0.005) and chronic (13.6 +/- 2.5 to 16.7 +/- 1.0 p < 0.05) phase. Additionally, work (watt) attained at AT increased significantly from control during both acute (33.6 +/- 19.2 to 52.6 +/- 30.2 p < 0.005) and chronic (35.8 +/ 25 to 49.3 +/- 15 p < 0.05) phase. Pressure-rate-products (PRP, x 10(2) mmHg/min) at AT increased significantly from control during the acute phase (119 +/- 35 to 240 +/- 50 p < 0.005) alone. In the chronic phase, PRP decreased significantly at the work level equal to AT during control (from 207 +/- 41 to 187 +/- 39 p < 0.05). These data suggest that bunazosin has favorable acute and chronic effects on exercise capacity in patients with congestive heart failure. PMID- 1439276 TI - [A clinical study of postinfarction angina (PIA): the significance of electrocardiographic ST segment changes during anginal attacks]. AB - We studied the clinical significance of electrocardiographic ST segment changes during PIA attacks. Of 478 AMI patients admitted to the CCU of our hospital within 48 hours after onset, we evaluated 73 (15.3%) with PIA. According to electrocardiographic ST segment changes during PIA attacks, the patients were divided into three groups, namely ST elevation at the same infarction site (same site elevation group), ST depression at the same site (same site depression group), and ST depression at other sites (other site depression group), and their pathological condition was studied. There were 33 patients (45.2%) in the same site elevation group, 19 (26.0%) in the same site depression group, and 21 (28.8%) in the other site depression group. The predominant infarction areas were anteroseptal and inferior wall in the same site elevation group, NTMI in the same site depression group, and inferior wall in the other site depression group. PIA usually occurred within 4 days after the onset of infarction in the same site elevation group, and within 5-7 days in the other site depression group, but no uniform trend was observed in the same site depression group. With respect to the number of vessels showing disease, cases of single-vessel disease tended to predominate in the same site elevation group, while cases of three-vessel disease tended to predominate in the same site depression group and the other site depression group. Stenosis rates in the vessels responsible for infarction were high in the same site elevation group in the acute period. Prognoses were poorest in the same site depression group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439277 TI - [A case of hypereosinophilic syndrome exhibiting left ventricular systolic dysfunction]. AB - A 16-year-old woman suffering from bronchial asthma since 2 years previously was admitted to the hospital because of high grade fever, dyspnea, skin eruption and arthralgia. Laboratory data revealed pronounced eosinophilia with elevated immunoglobulin E value. A chest X-ray film showed cardiomegaly with pulmonary congestion. Left ventriculograms showed diffusely reduced motion of the left ventricle (LV). Various clinical symptoms and laboratory data were resolved shortly after the administration of corticosteroids, but the LV dysfunction persisted for at least three months. Left ventriculograms 2 years later disclosed a marked improvement of the LV wall motion. In both the acute and the chronic phase, endomyocardial biopsy of both ventricles revealed non-specific histological findings comprising disarrangement of myocytes and interstitial fibrosis, suggesting post-myocarditis. This case was characterized by LV dysfunction possibly due to eosinophilic myocarditis associated with hypereosinophilic syndrome, and by its functional improvement with long-term corticosteroid therapy. PMID- 1439278 TI - [Two cases of hypothyroidism with echocardiographic features similar to cardiomyopathy: one simulates hypertrophic and the other dilated cardiomyopathy]. AB - Two cases of hypothyroidism with echocardiographic features similar to cardiomyopathy were presented. In case 1 (a 68 year-old woman), moderate pericardial effusion and myocardial hypertrophy were observed on admission. In case 2 (a 69 year-old woman), dilation of the left ventricle, hypokinesis of the interventricular septum and the left ventricular free wall, and reduced left ventricular systolic function were observed on admission. These echocardiographic findings were similar to hypertrophic or dilated cardiomyopathy. In the two cases, after recovery to euthyroid state, these echocardiographic abnormalities returned to normal. We concluded that hypothyroidism led to a reversible hypertrophic or dilated cardiomyopathy, and that echocardiographic study was useful for diagnosis and for following up cardiac manifestations of hypothyroidism. PMID- 1439279 TI - [A case of nonbacterial thrombotic endocarditis presenting positive findings by two-dimensional echocardiography]. AB - A 55-year-old woman was admitted to our hospital because of left hemiparesis. Brain CT and cerebral angiography demonstrated cerebral embolism due to occlusion of the sphenoidal part of the right middle cerebral artery. Two-dimensional echocardiography revealed mitral valve vegetation measuring 10 x 7 mm and slight mitral-valve regurgitation. Blood cultures were negative. She developed disseminated intravascular coagulation. Chest roentgenography and abdominal ultrasonography showed multiple liver and lung tumors, but she died before the primary lesion was detected. At autopsy, adenocarcinoma of the gall bladder was found. Friable vegetation was attached to the auricular surface of the mitral valve. Microscopic examination confirmed the diagnosis of nonbacterial thrombotic endocarditis. Although echocardiography is an important tool for diagnosing nonbacterial thrombotic endocarditis, few reports have described echocardiographic detection of nonbacterial thrombotic endocarditis. Because vegetation of nonbacterial thrombotic endocarditis is smaller than that of infective endocarditis (less than 3 mm), it is difficult for echocardiography to detect nonbacterial thrombotic endocarditis. Thus, a negative examination does not exclude the possibility of nonbacterial thrombotic endocarditis. To make an antemortem diagnosis of nonbacterial thrombotic endocarditis, we must perform echocardiography carefully in cases of cerebral infarction with carcinoma and/or DIC. PMID- 1439280 TI - [A case of an unusual type of coarctation of the aorta terminating in the complete obstruction]. AB - A 19 year-old girl with an unusual type of coarctation of the aorta terminating in complete obstruction is presented. At the age of 5 years, she was diagnosed by aortography to have coarctation of the aorta of type IV C according to Edward's classification. No surgical treatment was performed at that time because her growth was good and she didn't have hypertension. During the follow-up period, marked hypertension developed, and she was readmitted. The aortogram revealed a bicuspid aortic valve and total obstruction of the descending thoracic aorta at the site where coarctation was noticed previously. The abdominal aorta distal from the obstruction site was filled through rich collateral circulation. As these angiographic interval changes are very rare, we discussed the genesis of obstruction and operative indication by reviewing the literature. PMID- 1439281 TI - [Introduction to pressure support ventilation]. PMID- 1439282 TI - [Theory of pressure support ventilation]. PMID- 1439283 TI - [Evaluation of patient-ventilator interactions during pressure support ventilation using spring-loaded bellows type lung model]. PMID- 1439284 TI - [Ventilators which are designed for pressure support ventilation]. PMID- 1439285 TI - [Clinical advantage and limitation of pressure support ventilation]. PMID- 1439286 TI - [Are the first repetitive reentrant VPCs a trigger or an initiation of reentrant circuit for VPCs?: Evaluation by Holter ECG in patients with reentrant sustained ventricular tachycardia]. AB - To evaluate whether the first repetitive reentrant VPCs are a trigger or an initiation of a reentrant circuit for VPCs, we studied Holter ECGs in 13 patients with sustained ventricular tachycardia, the morphology of reentrant VPCs, the relationship between the coupling interval (N-V) and the first ventricular cycle length (V-V), and the relationship of the coupling interval (N-V) between single VPC and repetitive VPCs. In 7 patients who showed episodes of repetitive VPCs more than twice on one recording of Holter ECG, most of VPCs in the first and second beats were the same in shape (1195 out of 1466 episodes, 82%). No obvious relationship between the coupling interval (N-V) and the first ventricular cycle length (V-V) was found in 5 patients, whereas a weak inverse relationship (r = 0.32) was found in one patient, and a weak positive relationship (r = 0.38) was found in another patient. In addition, the coupling interval in repetitive VPCs was longer than that in single VPCs in 4 out of 7 patients. These results imply that, in most cases, the first VPC is the expression of initiation of a reentrant circuit for repetitive reentrant VPCs developing spontaneously. PMID- 1439287 TI - [Detection of ventricular late potentials comparison of 4 commercial high resolution systems]. AB - The purpose of this study was to evaluate the methodologic problems of noninvasive registration of ventricular late potentials. METHODS: we compared the results obtained in the same patients with four different systems which were Marquette MAC1, MAC12, ART LP101 and FUKUDA VCM 3000. Filtering was employed digital forward direction, 100-300 Hz in MAC1, digital FFT, 40-250 Hz in MAC12, digital, bidirectional, 40-250 Hz in ART and analogue, forward direction 40-300 Hz in FUKUDA VCM 3000. DEFINITION OF LATE POTENTIALS (LPs): Filtered QRS duration (FQRSD) was 120 msec or more, root mean square voltage in the last 40 msec (RMSV) was 15 microV or less in MAC12 and ART. FQRSD was 130 msec or more, RMSV was 15 microV or less in FUKUDA. FQRSD was 20 msec or more after QRS obtained from low resolution leads in MAC1. SUBJECTS: 163 patients [control 13, PVCs 23, myocardial infarction 55, others 51, IVCD (RBBB, LBBB, IVCD) 21] were included in this study. RESULTS: 17.6% of all patients (except for IVCD) showed LPs with MAC12, 20.0% with ART, 30.3% with FUKUDA, and 14.1% with MAC1. 23.1% of the control group showed LPs with MAC12 and FUKUDA, but no cases showed LPs with ART and FUKUDA. 4.3% of the PVC group showed LPs with MAC12, 13.0% with ART and FUKUDA, but no cases showed LPs with MAC1. 25.5% of the myocardial infarction group showed LPs with MAC12 and MAC1, 30.9% with ART and 36.3% with FUKUDA. All four methods gave corresponding results in 65.4% of patients, 7.0% positive and 58.4% negative findings. FQRSD of MAC12, ART and FUKUDA was 110.2 +/- 18.1 msec, 105.2 +/- 20.4 msec and 125.8 +/- 22.8 msec respectively. Correlation coefficient (r value) in FQRSD was 0.90 between ART and MAC12, 0.74 between ART and FUKUDA, and 0.75 between FUKUDA and MAC12. RMSV of MAC12, ART and FUKUDA was 49.2 +/- 30.2 microV, 43.7 +/- 37.8 microV and 22.5 +/- 10.6 microV respectively. R value in RMSV was 0.59 between ART and MAC12, 0.38 between ART and FUKUDA and 0.43 between FUKUDA and MAC12. R value in high frequency low amplitude signals duration under 40 microV of LPs positive patients in MAC1 was 0.51 between ART and MAC 12, 0.18 between MAC12 and MAC1, and 0.32 between ART and MAC1. Most of the differences result from a different interpretation of the tracings. Especially LPs far from QRS offset could be registered with neither MAC12, ART nor FUKUDA. PMID- 1439288 TI - [The effect of acebutolol and metoprolol on noninvasive ambulatory blood pressure monitoring system in essential hypertension]. AB - We compared the antihypertensive effects of acebutolol and metoprolol during 2-4 weeks of treatment in patients with mild to moderate essential hypertension. Acebutolol (n = 12) significantly decreased conventionally measured blood pressure from 173/100 mmHg to 148/86 mmHg (p less than 0.005), and metoprolol (n = 11) decreased it from 164/106 mmHg to 138/87 mmHg (p less than 0.01). Based on data derived from automated 24-hour ambulatory blood pressure monitoring, both drugs significantly decreased the blood pressure in the early morning (5:00 10:00). Moreover, in the metoprolol group, there were significant falls in day time blood pressure (7:30-19:30) and night-time blood pressure (23:00-7:00). In contrast, acebutolol showed significant antihypertensive effect on day-time blood pressure, but not effect on night-time blood pressure. The study confirmed the efficacy and character of metoprolol and acebutolol. We must choose an effective beta-blocker when using an automated 24-hour ambulatory blood pressure monitoring system to get adequate blood pressure reduction for the whole 24 hours. PMID- 1439289 TI - [Ultrasonic tissue characterization in hypertrophic cardiomyopathy: analysis of three-layered appearance of the ventricular septum by apical approach]. AB - In normal hearts, two-dimensional echocardiography from the apical window displays the left ventricular wall as a three-layered appearance (TLA): central bright layer and bilateral sonolucent zones. The TLA is considered to reflect the normal myocardial architecture: the predominant latitudinal fiber bundles of the midwall layer, and longitudinal or oblique ones on both sides. We analysed the TLA of the ventricular septum in 20 normal subjects, 20 patients with left ventricular hypertrophy due to pressure load (LVH), and 81 patients with hypertrophic cardiomyopathy (HCM). Of the 81 HCM patients, the layering was often obscure or absent in 53 (65%), whereas LVH patients showed clear TLA as well as normal hearts. In patients with severe layering disorder (n = 30), the age at diagnosis was lower (40 +/- 15 vs 50 +/- 12, p less than 0.05), and familial occurrence (53 vs 11%, p less than 0.01) and severe functional limitation (NYHA greater than or equal to III) were more common (27 vs 4%) than in those with clear TLA (n = 28). The disturbed layering detectable by echocardiography may reflect the disorder of basic myocardial fiber architecture in the ventricular septum, and is likely to become a useful marker of the pathologic severity of the disease. PMID- 1439290 TI - [Electrophysiologic effect of a new Ca(2+)-antagonist, TA-3090 on supraventricular tachycardia and conduction system]. AB - We investigated the effect of a new Ca-antagonist, TA-3090 on supraventricular tachycardia (SVT) and conduction system, comparing it with the effect of Diltiazem Hydrochloride, in 11 patients who had paroxysmal SVT attacks. Seven of the 11 patients presented atrioventricular reentrant tachycardia (AVRT) via retrograde concealed conduction through an accessory pathway, and the others presented AV nodal reentrant tachycardia (AVNRT). After SVT was induced by means of programmed electrical stimulation at high right atrium, TA-3090 (0.1 mg/kg body weight) or Diltiazem (0.2 mg/kg) was administered intravenously for 3 minutes. TA-3090 terminated nine of 11 SVTs, while Diltiazem terminated four of 4 SVTs. On termination of SVT, both drugs interrupted A-H conduction during AVRT and the slow pathway during AVNRT. After TA injection, five of 11 SVTs could not be induced by programmed electrical stimulation, while two of 4 SVTs could not be induced after Diltiazem. In AVRT, three patients in which TA-3090 prevented SVT induction had a longer AV node effective refractory period than that of the others in which TA-3090 could not prevent SVT (330 +/- 46 vs 210 +/- 24 msec, p less than 0.01). However, SVT was induced more easily than before in three of the 11 patients treated with TA-3090 administration, and in one of the 4 patients treated with Diltiazem administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439291 TI - [Augmentation of left ventricular slow filling in hypertrophic cardiomyopathy]. AB - To investigate the significance of augmentation of left ventricular slow filling, trans-mitral flow (TMF) was echocardiographically observed through pulsed Doppler method in 116 patients with hypertrophic cardiomyopathy (HCM), 74 with dilated cardiomyopathy (DCM), 27 with mitral regurgitation (MR), 86 with old myocardial infarction (OMI) and 80 normal controls (C). The slow filling-wave (SFW) in TMF was defined as the filling wave with obvious peak velocity during slow filling phase. The peak velocities (E, A, S) of the early filling, the atrial contraction and the slow filling waves were measured. The SFW was divided into two patterns according to the S and E ratio: large SFW (S/E greater than or equal to 1/2) and small SFW (S/E less than 1/2). 1) The small SFW was more frequently, but not significantly, observed patients with MR (37%) than in normal subjects (18%), patients with HCM (10%), DCM (4%) and OMI (7%). However large SFW was observed in 16 patients (14%) with HCM, but not in normal subjects and patients with other cardiac diseases excluding one patient with DCM. 2) In normal subjects and patients with DCM, OMI and MR, those with small SFW had larger E and smaller A/E than those without small SFW. However in patients with HCM, there was no difference in these indices (E and A/E) according to whether the patients were with or without SFW. 3) In HCM, patients with large SFW had significantly smaller E and significantly larger isovolumic relaxation time than those without SFW. Thus, appearance of the large slow filling wave, which might be caused by abnormal relaxation of the left ventricle, was frequently observed in patients with HCM. PMID- 1439292 TI - [Long-term follow-up of clinical features and ECG changes in 50 patients with HCM]. AB - We studied the relation of ECG changes during the clinical course in patients with hypertrophic cardiomyopathy (HCM). Fifty patients with HCM were categorized in two groups; 20 patients with, and 30 patients without signs of deterioration of clinical state. The changes between the first and the final ECG were compared in these two groups. The average follow-up period was 7.6 years. Twenty patients with clinical deterioration presented increase in QRS intervals (0.06----0.071 sec, p less than 0.025), decrease in voltage of RV5 (2.81----2.38 sec, p less than 0.025), increase in newly developed abnormal Q waves, and P wave changes. In contrast to these cases, 30 patients without clinical deterioration presented no significant ECG changes. Amplitudes of the negative T wave were unchanged in both groups. We conclude that electrocardiographic observations proved to be useful for predicting clinical features in patients with HCM. PMID- 1439293 TI - [Clinical value of PMN elastase activity before reperfusion therapy in acute myocardial infarction: comparison with clinical characteristics, reperfusion events and myocardial damage]. AB - Many recent studies demonstrate that neutrophils may be involved in the genesis and propagation of myocardial ischemia and reperfusion injury. Clinical value of PMN elastase activity before reperfusion which is released from activated polymorphonuclear leucocyte were evaluated in 30 patients with acute myocardial infarction. 19 patients with normal or moderately elevated PMN elastase activity (G1: less than 200 micrograms/l) revealed similar clinical characteristics before reperfusion therapy, compared to 11 patients with extremely high PMN elastase activity (Group 1: greater than or equal to 200 micrograms/l). But Group 1 represented fewer incidence of reperfusion events (Group 1 2/19, Group 2 7/11, p less than 0.01) such as arrhythmia, BP down, re-elevation of ST segments, and increased chest pain just after reperfusion, and higher incidence of salvaged myocardium in the risk area (Group 1 5/11, Group 2 4/19 p less than 0.1) evaluated by Tc-99m PYP, T1-201 dual SPECT, than Group 2. Wall motion analysis also showed that both global and regional wall motion were severely depressed in Group 2 compared with Group 1 (Group 1: Global EF 66.6 +/- 13.5, Extent 26.5 +/- 17.4, Severity 63.1 +/- 48.5, Group 2: Global EF 51.2 +/- 10.6, Extent 40.1 +/- 16.3, Severity 112.8 +/- 55.5, p less than 0.01 for Global EF, Extent, and p less than 0.05 for Severity). These data suggest that leucocyte activation before reperfusion may play important role in the genesis of reperfusion injury. PMID- 1439294 TI - [A case of middle aged women with isolated left coronary ostial stenosis]. AB - A-50-year-old woman was admitted to our hospital for the examination of exertional chest pain. She had no coronary risk factors. No hormonal disorders were observed. Physical and laboratory examinations revealed that she had not suffered from syphilis or aortitis syndrome or any other inflammatory diseases. An exercise electrocardiogram (Master's test) demonstrated ST segment depression in V3-6, II, III and a VF. On coronary angiography, a 75% stenosis of the left coronary ostial stenosis was found, but no abnormality was found in other arterial trees. The patient was diagnosed as having isolated coronary ostial stenosis. She underwent coronary bypass surgery from the aorta to the circumflex artery and the anterior descending coronary artery. She is now completely asymptomatic. A review of the literature together with this patient reveals the following characteristics of patients with isolated coronary ostial stenosis. Firstly, the patients are almost always middle aged woman with no coronary risk factors. Secondly, the involved coronary artery is the left main coronary artery, so its obstruction results in a serious condition. Therefore, though its pathogenesis remains to be determined, isolated left coronary ostial stenosis seems to be a distinct clinical entity. PMID- 1439295 TI - [A case report of two mitral valve aneurysms with one perforation after two attacks of infective endocarditis]. AB - Aneurysms of the mitral valve complicating infective endocarditis (IE) are uncommon. The patient was a 57-year-old man who was admitted to our hospital for a precise examination of heart failure. One year before, the first two dimensional echocardiography showed an aneurysm of the anterior mitral leaflet possibly due to a previous attack of IE. Doppler color flow mapping detected a regurgitant jet from the mitral valve aneurysm into the left atrium during systole, which suggested perforation of the aneurysm, and an aortic regurgitant jet flowing against the anterior mitral leaflet. Because the patient's family refused cardiac catheter examination and surgery, we treated him in the out patient clinic. A few weeks before his admission, he had discontinued taking diuretics because of uncomfortable urinary frequency. He gradually developed the symptoms of heart failure and entered our hospital. IE was suspected because of leucocytosis and slight fever. Two-dimensional echocardiography revealed a new aneurysm of the anterior mitral leaflet without perforation, located in the distal part of the old aneurysm. This time, his family consented to the surgical treatment. Aortic and mitral valve replacement was successfully performed. It was pathologically confirmed that the two mitral aneurysms had been caused by IE. PMID- 1439296 TI - Effect of hyaluronidase on interstitial pressure response to edema in air inflated rabbit lung. AB - The response in perivascular interstitial pressure to water accumulation was measured in air-inflated isolated rabbit lungs. The blood vessels and trachea of isolated lungs were cannulated and the vascular cannulas were connected to a reservoir filled either with a 3% albumin in saline solution (control) or with hyaluronidase in the albumin solution (treated). The lungs were inflated to 5 cmH2O transpulmonary pressure and the vascular reservoir elevated to a height of 7-10 cm above the lung base. The reservoir was suspended by a load cell which measured liquid accumulation in the lung. As the lung gained weight, interstitial pressure was measured by the micropuncture technique in the interstitium surrounding a vein near the hilum of an upper lobe. In control lungs, interstitial pressure increased monotonically with time from a value slightly below 0 cmH2O (pleural pressure) to a value of approx. 3.0 cmH2O by 5 h. In treated lungs, interstitial pressure increased more slowly to a value of approx. 1.5 cmH2O by 5 h. Interstitial compliance, the change in weight gain divided by the change in interstitial pressure, was 1.2 g.(g lobe wt)-1.cmH2O-1 for the control lungs and 2.9 for the treated lungs. A two-compartment electrical analog model representing the perivascular interstitium and alveolar liquid space was developed to simulate the data. The analysis indicated that in the control lungs, perivascular interstitial conductance and compliance were 5-fold and 15-fold smaller than those of the alveolar liquid space, respectively. The slower rise in interstitial pressure with water accumulation in the treated lungs was attributed to an increased compliance of the alveolar liquid space. The effect of hyaluronidase on the alveolar liquid space was to increase its compliance 2.4 fold with little change in its fluid resistance. PMID- 1439297 TI - Respiratory mechanics of the coatimundi and woodchuck. AB - The coatimundi breathes with a large tidal volume and relatively short TE/TTOT while the woodchuck has a relatively long TE/TTOT compared to other mammals. Hence, the respiratory mechanics of the coatimundi and woodchuck were studied to determine whether mechanics play any role in the differences in breathing pattern observed in these two mammals of similar body size. Although static respiratory system compliance was less and lower airway resistance was greater in the woodchuck compared to the coati there was no significant difference in deflationary time constant that could contribute to the difference in expiratory time. Both species exhibit less compliant chest walls than would be predicted for animals this size (4.5 and 5 kg) and the coati lung compliance is greater than that of the woodchuck or the prediction. The large tidal volume in the coati may be attributed in part to the large lung volume of this species (2.2 times the allometric prediction). The differences in breathing pattern are more likely related to differences in the control of breathing (i.e. regulation of expiratory airflow and inspiratory onset) than to differences in respiratory mechanics. PMID- 1439298 TI - Chemosensitivity and breathing pattern regulation of the coatimundi and woodchuck. AB - An analysis of breathing pattern regulation was carried out on the coatimundi and woodchuck who represent two different volume-time patterns. It was found that the coati, with a short expiratory time as a fraction of total breath time, TE/TTOT, has a greater sensitivity to CO2 as represented by the slope and threshold of its ventilatory response. Breathing air the coati maintains post-inspiratory inspiratory activity (PIIA) of the posterior cricoarytenoid (PCA) through 51% of expiration, while the woodchuck, who is less sensitive to CO2 and has a long TE/TTOT, exhibits no PIIA of the PCA. The woodchuck also has a greater incidence and duration of end-expiratory pauses (or delayed inspiratory onset). The woodchuck does not demonstrate the usual inverse relationship between VT and TE in response to 5% CO2 and does not recruit PIIA of the PCA at this level of CO2. These data confirm the importance of CO2 chemosensitivity in regulation of TE. It is further demonstrated that interspecific differences in chemosensitivity among three mammals of the same size are reflected in regulation of TE but not in inspiratory 'drive' (as indicated by mean inspiratory flow, VT/TI). PMID- 1439299 TI - High intensity exercise training-induced metabolic alterations in respiratory muscles. AB - Limited information exists concerning the effects of high intensity interval exercise training (HIET) on metabolic alterations in both inspiratory and expiratory muscles. To test the hypothesis that HIET will improve the oxidative capacity of the diaphragm and major expiratory muscles, we examined Krebs cycle and beta oxidation enzyme activities in the diaphragm and three groups of expiratory (abdominal) muscles in rats subjected to 12 weeks (5 days.wk-1) of treadmill exercise. Two groups of female Sprague-Dawley rats (age ca 120 days) were studied: (1) HIET group (n = 10; animals performed 6 x ca 5-min running intervals.day-1 at ca 90-95% VO2max); (2) sedentary control group (n = 7). When compared to controls, HIET resulted in significantly elevated (P less than 0.05) activities of 3-hydroxy-acyl-Co-A dehydrogenase (HADH) and citrate synthase (CS) in the costal diaphragm, rectus abdominus, external obliques, and the plantaris muscles. In contrast, training did not increase (P greater than 0.05) the activities of CS or HADH in the crural diaphragm or the internal obliques/transversus abdominus muscles. By comparison, the training-induced increases in oxidative capacity (e.g., CS activity) in the costal diaphragm, rectus abdominus, and external obliques were relatively small (ca 23, 10, 12%, respectively) when contrasted to the exercise-induced increase in CS activity in the plantaris muscle (ca 47%). We conclude that HIET results in small but significant improvements in the oxidative and beta oxidation capacities of the costal diaphragm and at least two abdominal expiratory muscles. PMID- 1439300 TI - Activity of abdominal muscle motoneurons during hypercapnia. AB - Our purpose was to examine the influence of hypercapnia on the activity of motoneurons innervating the transversus abdominis and internal oblique abdominal muscles, and of integrated phrenic and abdominal motor nerve activities. Studies were done in nine adult cats that were decerebrated, vagotomized, thoracotomized, paralyzed and ventilated mechanically. Of 42 motoneurons examined, 24 showed strong respiratory modulation (RM neurons), with the discharge confined primarily to the central expiratory period. The remaining 18 motoneurons discharged tonically, and failed to show respiratory modulation even at increased levels of central respiratory drive. Hyperoxic hypercapnia augmented the activities of the phrenic and abdominal nerves and increased the early expiratory discharge frequency of the RM neurons. The hypercapnia-induced increase in firing frequency during early expiration was accompanied by a corresponding decline in late expiration, and a virtual abolition of the inspiratory activity in the few neurons that discharged in this phase under normocapnic conditions. Finally, hypercapnia induced an increase in the number of spikes generated during each expiratory period in about half of the RM neurons, whereas the remaining cells showed a decrease. Thus, the increased peak activity of the integrated whole abdominal nerve burst with hypercapnia was brought about by a shift in the temporal pattern of motoneuron firing, or by an increase in the number of spikes generated during the expiratory period. The steep rate of rise and the pronounced early expiratory peak observed in the integrated abdominal nerve burst during hypercapnia in this preparation are consistent with the increase in motoneuron firing frequency during the early stages of the expiratory phase. PMID- 1439301 TI - Diaphragmatic fiber type specific adaptation to endurance exercise. AB - Recent evidence suggests that exercise training results in a significant improvement in the oxidative capacity of the mammalian diaphragm; however, limited data exist concerning which diaphragmatic fiber types are metabolically altered due to training. To test the hypothesis that exercise training increases the oxidative capacity of diaphragmatic type I and IIa fibers only, we examined the effects of endurance training on the fiber type specific changes in oxidative capacity, cross-sectional area, and capillarity of the costal diaphragm. Female Fischer-344 rats (age ca 180 days) were divided into either sedentary control group (n = 6) or an exercise training group (n = 6). The trained animals exercised for 10 wks on a motor-driven treadmill (60 min.day-1; 5 days.wk-1) at a work rate equal to ca 55-65% VO2max. Capillaries were identified histologically and fiber types determined using ATPase histochemistry. Fiber cross-sectional area (CSA) and succinate dehydrogenase (SDH) activity in individual fibers were measured using a computerized image analysis system. Compared to control animals, training did not increase the capillary to fiber ratio in any diaphragm fiber type (P greater than 0.05); however, training increased capillary density (capillary No./CSA) in type IIa fibers due to a reduction in cell CSA (P less than 0.05). Further, training resulted in significant (P less than 0.05) increases in total diaphragmatic SDH activity (delta increase = 17.5%) and an increase in SDH activity in both type I (delta increase = 14%) and IIa fibers (delta increase = 17.4%). In contrast, training did not alter (P greater than 0.05) SDH activity in type IIb fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439302 TI - Effect of dopamine on ventilatory response to incremental exercise in man. AB - We investigated whether dopamine, an inhibitory neuromodulator in the carotid body, would alter the ventilatory response typically associated with metabolic (lactic) acidosis during exercise. Six subjects performed incremental cycle ergometer exercise to exhaustion during infusions of dopamine (3 micrograms.kg 1.min-1) or saline. Ventilation and pulmonary gas exchange were computed breath by-breath; arterialized venous blood was collected every 90 sec for measurement of lactate, potassium and blood gases. The resting ventilatory response to an isocapnic step decrease in end-tidal PO2 to 50 Torr was used as an index of carotid body drive. Dopamine diminished the hypoxic ventilatory response but had no effect on the ventilatory response during exercise. Peak lactate, potassium, and ventilation were unaffected by dopamine, and the degree of respiratory compensation for the metabolic acidosis was the same as in control experiments. Therefore, either the carotid bodies respond differently to hypoxia than to acute metabolic acidosis and/or hyperkalemia during heavy exercise, or the carotid bodies are not the sole mediators of hyperventilation above the lactate threshold. PMID- 1439303 TI - Neural respiratory responses to cortically induced seizures in cats. AB - Seizure activity can lead to profound respiratory stimulation in spontaneously breathing animals with intact respiratory feedback mechanisms (Paydarfar et al., Am. J. Physiol. 260, R934, 1991). The present study was designed to test the hypothesis that peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea. Studies were performed in 16 anesthetized, vagotomized, glomectomized cats whose end-tidal PCO2 (PETCO2) was kept constant. Integrated phrenic nerve activity was used to represent respiration. Seizures were induced by injection of penicillin into the parietal cortex and electrocorticographic (ECoG) and biceps femoris nerve activities, arterial pressure, airway PCO2 and brain temperature were recorded continuously. Progressive seizure activity was associated with progressive increases of respiratory frequency and peak phrenic activity, despite constancy of PETCO2 and brain temperature. Patterns of entrainment were identified among ECoG spikes, biceps femoris nerve and phrenic nerve activities. Phrenic nerve activity became highly irregular during generalized ictal seizures and ceased to respond to changes of PETCO2. Acute intercollicular decerebration in all experiments resulted in normalization of respiratory rhythm even while ictal ECoG activity continued. We conclude that stimulation of breathing during seizures occurs in the absence of respiratory feedback mechanisms. The findings suggest that an important cause of the respiratory response is a feedforward mechanism, whereby activation of subcortical structures above medulla and pons results in stimulation of breathing. PMID- 1439304 TI - Angiotensin II potentiates neurally mediated contraction of rabbit airway smooth muscle. AB - The effect of angiotensin II (AT II) on cholinergic neurotransmission in rabbit tracheal segments was studied under isometric conditions in vitro. AT II concentration-dependently potentiated the contractile response to electrical field stimulation (EFS), and caused a leftward shift of the frequency-response curves for EFS, so that the stimulus frequency required to produce a half-maximal effect (ES50), decreased from 7.0 +/- 0.1 to 3.0 +/- 0.1 Hz (P less than 0.01). In contrast, the contractile response to acetylcholine was not affected. Non peptide AT II receptor antagonist CV-2961 attenuated the effect of AT II on the EFS-induced contraction. Pretreatment of tissues with thiorphan or phosphoramidon did not alter the action of AT II. Thus, AT II may prejunctionally potentiate the neurally-mediated contraction of airway smooth muscle through activation of AT II receptors on the cholinergic nerve terminals, and this effect may not be modulated by endogenous neutral endopeptidase. PMID- 1439305 TI - Opsonized zymosan decreases cytoplasmic motility of alveolar macrophages in dogs. AB - To examine the mechanisms of changes in alveolar macrophage (AM) activities caused by phagocytic stimulus, we studied the effect of opsonized zymosan (OZ) on cytoplasmic motility (CM) of AM from dog lungs in vitro. Four days after the instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the lower lobe bronchus, AM were harvested by broncho-alveolar lavage. AM were adhered to the bottom of plastic vials (10(6) cells of AM per each vial). Remanent field strength (RFS) from the AM containing Fe3O4 particles was measured immediately after magnetization. RFS decreased with time due to particle rotation (relaxation), which is related to cytoplasmic motility of AM. OZ (1-500 micrograms) decreased lambda 0 (the relaxation rate for the first min) in a concentration-dependent fashion. Neither BW755C (10(-5) M), indomethacin (10(-6) M), leupeptin (10(-5) M), bestatin (10(-5) M), nor superoxide dismutase (1000 U/ml) inhibited OZ (500 micrograms)-induced inhibitory effects on lambda 0, suggesting that cyclooxygenase and lipoxygenase products, serine, thiol enzymes, aminopeptidase and superoxide anion wer not responsible for OZ-induced effects. OZ (500 micrograms) significantly increased the intracellular concentration of Ca2+ (P less than 0.01). Likewise, OZ (500 micrograms)-induced effects on lambda 0 of AM were significantly inhibited by replacement of the medium with a Ca2+ free solution (P less than 0.01). These results imply that opsonized zymosan inhibits cytoplasmic motility of AM via external calcium influx. PMID- 1439306 TI - [Systemic-psychodynamic model for family evaluation]. AB - In this paper a family evaluation instrument called systemic-psychodynamic family evaluation model is described. Also, the second stage of the validation study of this instrument is presented (which deals with the inter-observers variation). Twenty families were studied. They were assessed always by the same interviewers designated as experts. They are all family therapy specialists and their assessment was used as the evaluation reference standard or "gold standard". The observers were psychiatrists without previous training in family therapy. For the purpose of the interview, both experts and observers were blind to the medical diagnosis of the patients. During the first stage of the validation study the observers did not have a reference guide which resulted in a low concordance rating. For the second stage, a 177 item guide was used and a considerable increase in the concordance rating was observed. Validation studies like the one used here are of considerable value to increase the reliability and further utilisation of evaluation instruments of this type. PMID- 1439307 TI - Rapeseed diet and hepatocyte hypertrophy: an experimental morphometric study. AB - A previous study suggested that a rapeseed diet induced hepatocellular hypertrophy in normal albino rats. In the present study morphometry confirmed that a rapeseed diet produces hepatocytic hypertrophy which, according to cytological findings, is primarily due to an increase in the cytoplasmic area. A combination of a rapeseed diet and the administration of carbon tetrachloride (CCl4) also led to hepatocellular hypertrophy but the histological picture of the cirrhosis was similar to the one in control animals receiving CCl4 alone. The fact that the hypertrophy was primarily due to organelles supports the idea that a component or components of the rapeseed may modify protein turnover in the parenchyma of the liver. PMID- 1439308 TI - [Role of liver biopsy in the diagnosis of prolonged cholestasis in infants]. AB - Liver biopsy in the diagnosis of the results of a retrospective analysis of percutaneous liver biopsy in the differential diagnosis of prolonged cholestasis in infancy are reported. We compare the clinical features, serum bilirubin levels, hepatobiliary scintigraphy and histology in two groups of patients. One group of 56 patients had extrahepatic biliary obstruction (biliary atresia: 42; choledochal cyst: 9; extrinsic obstruction: 4; Caroli's disease: 1). Another group of 54 children had intrahepatic cholestasis with patent biliary tract (hepatitis: 38; non-specific cholestasis: 14; cirrhosis: 2). The percutaneous liver biopsy was better than the other procedures to differentiate biliary atresia from hepatitis. We conclude that percutaneous liver biopsy should be carried out in children with prolonged cholestasis when other non-invasive procedures have not ruled out extrahepatic biliary obstruction and before any surgical exploration of the biliary tract is performed. PMID- 1439309 TI - [Prognostic importance of beta-2-microglobulin in multiple myeloma]. AB - Beta 2 microglobulin is a low molecular weight protein found on the surface of all nucleated cells: it is the light chain of the HL-A histocompatibility complex. The increased levels of serum beta 2 microglobulin in patients with multiple myeloma have been associated with a poor prognosis. Pretreatment levels of serum beta 2 microglobulin were estimated in 70 previously untreated patients with multiple myeloma. In a multivariate analysis, serum beta 2 microglobulin levels and stage were the most significant prognostic factors for survival independent of other risk factors associated with a worse prognosis. There was a clear difference in survival duration observed between the patients with a high pretreatment level of beta 2 microglobulin and stage III (none alive at 5 years) compared with patients with normal levels and stage I (80% alive at five years) (p less than .001). We conclude that pretreatment-beta 2 microglobulin level is one of the most useful prognostic factors in patients with multiple myeloma. PMID- 1439310 TI - [Adjuvant chemotherapy in gastric cancer. Experience at the National Institute of Nutrition]. AB - The cases of gastric carcinoma treated with surgery plus chemotherapy (FAM) at the Instituto Nacional de la Nutricion (INNSZ) in Mexico City from January 1979 to December 1988 were reviewed. In 322 patients seen in this period, only in 12.4% (40 patients) it was possible to undertake curative resection; of these, twenty two received adjuvant FAM (fluorouracil, 600 mg/m2 IV days 1,2,3; doxorubicin, 30-35 mg/m2 day 1; and mitomycin-C, 10 mg/m2 in three days). Twenty patients were in stage III and two in stage II. At a median follow-up of five years, ten patients have relapsed; of these, eight died from progressive neoplasia; one is alive with no evidence of disease 24 months after receiving combined chemotherapy with 5-fluorouracil, cisplatinum and adriamycin, and one is alive with the disease. Nine patients (40.5%) are alive with no evidence of relapse 30 to 114 months after initial surgery. One patient died from unrelated causes with no evidence of relapse. Two individuals were lost to follow up at 9 months and 28 months, without evident malignant disease at the time of last consultation. The median survival was 61 months with a 51% estimated overall survival at five years. None of the prognostic factors analyzed were significantly associated with recurrence: number of metastatic lymph nodes; number of cycles of chemotherapy; interval between surgery and chemotherapy; and intraoperative blood transfusions requirements, although there was a tendency to relapse in the majority of the patients who received intraoperative blood transfusions as compared with the untransfused (five years disease free survival of 18% vs 64% respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439311 TI - [Clinical, cytogenetic, endocrinological and histological studies in true hermaphrodites]. AB - The clinical, cytogenetic, endocrinological and histologic features of nine mexican patients with true hermaphroditism are reported. Ages at admission ranged from 10 months to 27 years; in seven cases a male sex of rearing was documented, being 46,XX (n = 6) the most frequent karyotype. Basal levels of gonadotrophins, gonadal steroids, and the testosterone response to exogenous HCG varied depending upon age as well as with type and functional status of the gonadal tissue. However, ovarian tissue always preserved its function better than the testicular tissue did. In one of the patients who presented cyclic hematuria, spontaneous ovulation was documented by serum progesterone monitoring (progesterone = 4.3 11.0 ng/mL during luteal phase). Ovo-testis was the most common gonad present; in four cases bilateral ovo-testes were found. Internal genitalia varied depending on the existing gonad, although in all cases a uterus was found. These findings are in accordance with previous reports of individuals bearing true hermaphroditism in other populations. PMID- 1439312 TI - [Frequency and risk factors associated with metronidazole therapeutic noncompliance]. AB - OBJECTIVE: to determine the frequency and risk factors of non-compliance to oral metronidazole. STUDY DESIGN: comparative cross-sectional survey. STUDY UNITS: 111 patients who received oral metronidazole. SETTING CHARACTERISTICS: two medical units: one primary level unit and one secondary care unit of the Mexican Institute of Social Security. MEASUREMENTS: non-compliance was assessed by home interview and pill count. MAIN RESULTS: frequency of non-compliance was 55%. Risk factors for non-compliance were: female sex (OR = 3.0; p less than 0.05); side effects (OR = 3.1; p less than 0.05); low literacy (OR = 3.75; p less than 0.05). Stratified analysis showed no interaction between variables. CONCLUSIONS: frequency of non-compliance to metronidazole is high, and could affect the effectiveness of medical care. Female patients with low literacy and who suffer side effects are a high risk group for non-compliance. PMID- 1439313 TI - [Effect of the treatment of hyperthyroidism on the course of exophthalmos]. AB - The exophthalmos evolution in hyperthyroid patients was investigated: twenty patients were randomly assigned to treatment with radioiodine (group I followed 2 162 months) and 20 to treatment with thyroidectomy (group II followed 2-158 months). There was no correlation of sex age and follow up with exophthalmos evolution. In group I, exophthalmos improved in one patient (5%), did not change in ten (50%) and worsened in nine (45%). In group II it got better in six (30%), did not change in seven (35%) and got worse in seven (35%). The differences between the two groups were not statistically significant (p greater than 0.05). The postsurgical thyroid gamma-gram with one mCi of I-131 in group II showed absence of thyroid tissue in nine patients (45%) and remainders of the gland in 11 (55%) and apparently this did not influence the post treatment evolution. The length of pretreatment evolution did not influence the evolution post treatment. In summary, there was no correlation between exophthalmos evolution and kind of treatment in Graves' disease. PMID- 1439314 TI - [Dissolution of pancreatic calcifications with oral citrates in a woman with chronic idiopathic pancreatitis]. AB - Pain control is one of the most important objectives in the medical treatment of patients with chronic calcifying pancreatitis (CCP). It is generally accepted that pain in CCP is secondary to the obstruction of the pancreatic duct by calcifications, protein plugs and stenotic areas. Experimental studies have shown that calculi and protein plugs are soluble in citrates. We report here the case of a young non alcoholic woman with idiopathic CCP who after a pancreatojejunostomy developed again pain and pancreatic calcifications which were dissolved with oral citrates. The case confirms previous observations and illustrates the potential use of citrates in subjects with CCP. PMID- 1439315 TI - [Lung perforation by a small-bore enteral feeding tube]. AB - A 68 year old male with multisystemic disease, mainly lungs and heart, was treated with a cuffed endotracheal tube, mechanical ventilation and a 16 Fr Levin nasogastric tube for feeding; it was substituted 13 days later by a 2.3 mm, 8 Fr O'Brien KMI polyurethane small bore enteral feeding tube introduced with a guide wire. The feeding tube perforated his right lung and passed into the pleural cavity, either through the larynx or through a nonconfirmed tracheoesophageal fistula; signs for the supposedly correct position of the tube were positive. In patients with depressed sensoria, abnormalities of gag or cough reflexes, esophageal strictures, significant cardiomegaly or tracheoesophageal fistula, small bore enteral feeding tubes should be passed under direct vision by laryngoscopy or preferably by flexible endoscopy; adequate confirmation of the correct position requires a chest and an upper abdominal roentgenogram. PMID- 1439316 TI - [24-year-old male with fever, pancytopenia, and alterations in his state of consciousness]. PMID- 1439317 TI - [New approaches to the measurement of clinical competence]. AB - A new phase in the development of an instrument designed for the measurement of clinical competence is presented. The instrument (exam type) was previously validated; we report its use in three generations of students of a specialization course in internal medicine: those recently admitted to the course (group I); those finishing their first training year (group II) and those finishing the second year (group III). In the exam 304 out of the 600 questions included were classified as "experimental" (dealing with knowledge in internal medicine) and the remaining 296 questions corresponded to "control" questions (dealing with knowledge in other specialties). The variables considered in the exam were: 1) global result; 2) usage of diagnostic indicators; 3) omission of necessary procedures without a iatrogenic effect; 4) commission of unnecessary procedures without a iatrogenic effect; 5) omission of necessary procedures with resulting iatrogenic consequences; 6) commission of unnecessary procedures with resulting iatrogenic consequences; 7) global omission (variables 3 and 5); 8) global commission (variables 4 and 6); 9) global iatrogenesis (variables 5 and 6); 10) knowledge in nosology. Scores obtained by the three groups on the experimental questions differed in accordance with the respective time of clinical experience (group I obtained the lowest scores, group II showed intermediate scores, and group III showed the highest scores). Analysis of variance was significant (p less than 0.05) in variables 1, 2, 6, 8 and 9. The scores obtained by the three groups on the control questions were similar. In conclusion, we believe that this instrument is capable of detecting learning dependent on the time of clinical experience.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439318 TI - [Overview of erythrocyte glucose-6-phosphate deficiency]. AB - The cloning and sequencing of the G6PD gene has opened a new chapter in the characterization of the numerous G6PD variants described. Many which were thought to be different on the basis of their kinetic properties, are really the same whereas heterogeneity has been found in some which were thought to be homogeneous. We discuss with some detail variants A+, A- and the Mediterranean type. PMID- 1439319 TI - [Splenectomy in idiopathic thrombocytopenic purpura]. PMID- 1439320 TI - Pulmonary mycobacterial infections associated with neoplasia. AB - Patients with cancer are at increased risk for disease caused by mycobacteria when there is immunosuppression resulting from the underlying disease or its treatment. Pulmonary disease is usual with Mycobacterium tuberculosis or with mycobacteria other than M tuberculosis (MOTT) and atypical presentations with extrapulmonary dissemination occur frequently. No clinical features reliably distinguish between disease caused by M tuberculosis or MOTT. The incidence of M tuberculosis infection depends on a history of prior exposure in patients and on patterns of disease within hospitals and the surrounding community. Infection with different species of MOTT reflects their environmental prevalence. Diagnosis of mycobacterial infection can be clinically challenging and must be pursued aggressively. Despite recent improvements in clinical and laboratory methods, diagnosis of mycobacterial infection may take weeks. Recent increases in the incidence of M tuberculosis infection and the emergence of drug-resistant strains require heightened alertness to its diagnosis and careful epidemiological control measures to prevent continued spread of this contagion. M tuberculosis with routine antimicrobial susceptibility responds well to conventional therapy when initiated early. Prophylaxis of tuberculin positive patients is effective and should be started before immunosuppressive therapy. Guidelines for therapy of MOTT depend on the species isolated but remains poorly defined in most cases. There are several new compounds that may be useful for treatment of drug resistant species of MOTT. New methods for the rapid diagnosis, speciation, and epidemiological investigation of mycobacterial infection are being developed, and some are available for clinical application. Nonetheless, the timely diagnosis of mycobacterial disease in patients with cancer remains a challenge of increasing clinical importance. PMID- 1439321 TI - Pneumocystis carinii pneumonia among patients with neoplastic disease. AB - Pneumocystis carinii pneumonia (PCP) emerged in the 1980s as the most common opportunistic infection among patients with the acquired immunodeficiency syndrome (AIDS). Because of this, the presentation and clinical course of PCP has become well-known to many physicians. However, PCP continues to occur among patients not infected with the human immunodeficiency virus, generally those who receive immunosuppressive therapy as treatment for neoplastic disease. A review from Memorial Sloan-Kettering Cancer has shown that a new group of patients, those receiving corticosteroid therapy for brain neoplasm, are also at risk for the development of PCP and should receive PCP prophylaxis. Previously defined patient groups--people with acute lymphocytic leukemia or allogeneic bone marrow transplantation--also should continue to receive prophylaxis. In addition, the clinical course and outcome of patients with neoplastic disease who develop PCP may differ from those with AIDS and PCP: the disease may be much more fulminant among patients with neoplastic disease, and the mortality rate much higher, approaching 50% in the Memorial Sloan-Kettering Cancer Center series. Wider use of prophylaxis should decrease the frequency of this disease, whereas prompt initiation of therapy in patients with a compatible syndrome should help to improve mortality rates. PMID- 1439322 TI - Pulmonary infections after bone marrow transplant. AB - Pneumonia occurs in up to 50% of patients after bone marrow transplant and is the main cause of mortality. The patient may be predisposed to pulmonary complications by previous treatment and infections, by transplant conditioning and graft-versus-host disease prophylaxis regimens, and by prolonged severe immune-suppression. The period of greatest risk is within 3 months of transplant when focal or diffuse interstitial pneumonias may occur. The most common infectious etiologies are Aspergillus or other fungi and cytomegalovirus. Idiopathic, noninfectious, interstitial pneumonia occurring in this same period may represent treatment toxicity. Both fungal and cytomegalovirus infections have been associated with high mortality, but there has been significant success in treating cytomegalovirus with the combination of ganciclovir and immunoglobulin in recent years. Late bacterial pneumonia may occur more than 6 months after transplant because of prolonged immunedeficiency and functional asplenia. Prophylactic therapy to prevent the pneumonias anticipated after transplant should be an essential part of the care of the bone marrow transplant patient. PMID- 1439323 TI - An approach to the diagnosis of pulmonary infections in immunosuppressed patients. AB - The goal of this review is to provide an approach to the diagnosis of pulmonary infections in immunosuppressed patients. First, a framework will be provided to narrow the extensive list of possible infectious and noninfectious pulmonary complications. This can be accomplished by considering the underlying immune defect, the pattern of radiographic presentation, the rapidity of progression of radiographic infiltrates, the typical temporal pattern of infection in specific disease states, and the local epidemiology at one's institution. Next, the yields and potential complications of invasive and noninvasive diagnostic techniques for pulmonary infections are reviewed. Lastly, algorithms, which account for the pattern of radiographic presentation, the primary disease and its underlying immune defect and the anticipated yields and complications of diagnostic procedures, are provided as a suggested plan for the use of diagnostic techniques and the institution of therapy. PMID- 1439324 TI - Invasive pulmonary aspergillosis complicating neoplastic disease. AB - Invasive pulmonary aspergillosis is a necrotizing pneumonia that is most frequently seen in association with profound granulocytopenia as a consequence of cytotoxic chemotherapy that is used to treat hematologic neoplasms. There is considerable evidence that the incidence of this infection is increasing over the past decade as a result of improved medical support used in the management of "at risk" patients. Heightened clinical awareness coupled with advances in diagnostic techniques have led to earlier treatment and improved outcomes of this once uniformly fatal infection. Amphotericin B remains the treatment of choice; however, newer therapeutics (azoles) and strategies (combination chemotherapy, biological response modifiers) show promise as alternative regimens. Novel approaches in preventing the acquisition of pulmonary aspergillosis in the "at risk" patient are being explored. PMID- 1439325 TI - An independent application accuracy evaluation of stereotactic frame systems. AB - The purpose of incorporating stereotactic methodology into neurosurgical procedures is to consistently achieve a high degree of accuracy and precision in localizing intracranial targets. Therefore, the limits of resolution for the therapeutic intervention itself are a function of the accuracy and precision inherent to the particular stereotactic frame system itself. The total clinically relevant error (application accuracy) comprises errors associated with each procedural step, including imaging, target selection, vector calculation and the mechanical errors of stereotactic frames. To evaluate these parameters, a systematic error analysis was carried out in the 4 most commonly used CT compatible stereotactic devices: the Brown-Roberts-Wells, Cosman-Roberts-Wells, Kelly-Goerss Compass (modified Todd-Wells) and Leksell frames. Over 7,681 independent test measurements were made. The results suggest a potentially significant degree of error in application accuracy of all stereotactic instrumentation which is accentuated by imaging-associated error. These individual error values must be considered with every clinical use of stereotactic frames. PMID- 1439326 TI - A universal system for interactive image-directed neurosurgery. AB - Stereotactic methods confer great accuracy to intracranial target localization, but require strict adherence to a complex program of mechanical and computational maneuvers. A computerized, articulated, localizing 'arm' has been developed that frees the neurosurgeon of these constraints and provides a completely intuitive, 'user-friendly' interface. This universal system is independent of whatever localizing fiducial system is selected. The arm may be sterilized for intracranial use. A variety of intraoperative end effectors may be selected. The patient's CT/MR/PET scans are loaded into computer memory and a three-dimensional shaded surface wireframe diagram of the patient's head is displayed simultaneously with up to 3 independent sets of cross-referenced CT/MR/PET scan images on the intraoperative video screen. The arm's endpoint location and the directional vector are shown as cursors on the relevant scan slices, and change continuously as the surgeon moves the arm. Because the information is continuously updated, an unlimited number of targets and trajectories may be displayed throughout the operation. The arm has an ultimate design accuracy for end-point localization to within 0.1 mm throughout a target volume of 40 x 40 x 40 cm. The tested application accuracy of the first prototype model is 0.31 mm. In clinical use during 30 surgeries, its real-world application accuracy is 0.9 mm. This system provides stereotactic accuracy and universally compatible, intuitive, interactive operation. PMID- 1439327 TI - Further development and clinical application of the stereotactic operating microscope. AB - Implementation of a Vicom-VME image processing workstation for the frameless stereotactic operating microscope system has allowed an improved interpolation algorithm for more accurate reconstruction of three-dimensional data, the integration graphically of multimodality imaging information, an additional stereotactic graphics display outside of the microscope optics and optional three dimensional displays through communication with a Convex mini-supercomputer. A precision-milled coupling for reproducible attachment of the spark gap bracket to the microscope has eliminated the need for that transformation calculation during each case. Clinical utility has been greatest in providing navigational guidance to small subcortical or deep lesions and in defining the extent of preoperatively planned resection of larger, infiltrating tumors. Mean accuracy in the past 17 cases has been 3.5-6.5 mm. The frameless methodology has also enabled extracranial stereotactic surgical procedures in 7 patients. PMID- 1439328 TI - Stereotactic magnetic resonance angiography. AB - Visualization of the surgical trajectory with respect to the cerebral vasculature may enhance the safety of some stereotactic neurosurgical procedures. Traditional stereotactic angiography is tedious and, being an invasive procedure, poses some risk to the patient. A technique of projecting a stereotactically defined surgical trajectory onto magnetic resonance angiograms is presented. PMID- 1439329 TI - In vivo and in vitro study of the lesions produced with a computerized radiofrequency system. AB - For many years, radiofrequency-generated lesions have been used for the treatment of pain and abnormal movements. However, the reliability of this method has been questioned because of the variation in the size of lesions produced by the electrode at different times and temperatures. A 500-kHz radiofrequency generator with different electrodes was used to determine the size of lesions, using different time and temperature exposures. A computerized feedback mechanism kept the tip temperature constant during the production of the lesion, regardless of varying tissue impedance. Eight electrodes of different size and tip characteristics were evaluated at different temperatures and time settings, both in vitro and in vivo. Graphic display of the curves in time were obtained at 65, 70, 75, 80, 85 and 90 degrees C. The effects of thermo-coagulation were studied in vitro in fresh egg whites, using time intervals of 20, 40, 60, 80 and 100 s, and in vivo, in the subcortical white matter of 20 adult New Zealand white rabbits. Animals were sacrificed after 7 days. Lesions were photographed and measured under magnification. In all cases, the coagulated masses were ellipsoid, with regular, well-demarcated borders. A two-way statistical analysis of variance was done. The coagulum size increased with higher temperatures and with larger probes. The increase was significant in both diameter and length (p = 0.001). In contrast, the use of different times at the same level of temperature showed no significant increase in most of the electrodes. There were two statistical significant time effects, for both diameter and length, with the monopolar 2-mm electrode. The use of real-time monitoring with graphic display and the feedback information provided for the computerized control of power and current allows high precision of the temperature at the electrode tip during the production of the lesion. PMID- 1439330 TI - Positron emission tomography imaging-directed stereotactic neurosurgery. AB - The diagnostic yield of stereotactic biopsies depends upon safely sampling the most representative regions of masses. Potentially, localization information presently available from CT and MR scans might be improved by considering regional levels of cerebral metabolism by PET. In 10 selected stereotactic biopsies of intracranial mass lesions, PET scans were obtained using the Siemens CTI system; the Kelly-Goerss Compass system was used as the stereotactic development platform. PET-[18F]-fluorodeoxyglucose (FDG) images provided clinically significant information by appropriately directing biopsy efforts when CT and MRI was inconclusive or misleading. PET-FDG images can be successfully incorporated into routine image-directed stereotactic surgery. PMID- 1439331 TI - Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms. AB - Stereotactic ventroposterolateral pallidotomy in 46 parkinsonian patients resulted in a complete or almost complete and long-lasting relief of rigidity and hypokinesia in 91% of the patients. Good tremor effect was obtained in 80% of them. The L-dopa-induced dyskinesias, gait and speech improved in most patients. Complications were observed in 7 cases after 51 pallidotomies, i.e. 14% (partial homonymous hemianopia in 6 and transient dysphasia and facial weakness in 1). We believe that the good effect of surgery is based on interruption of some striopallidal or subthalamopallidal pathways. PMID- 1439332 TI - Three-dimensional whole-brain mapping. AB - The implementation and use of a computerized whole-brain mapping system which can be used in conjunction with MRI, CT, angiographic and other brain imaging techniques is described. Three mapping systems based upon common reference structures about the third and fourth ventricular core of the brain are used in conjunction with internationally recognized nomenclature to create a normalized whole-brain mapping system according to the Talairach/Tournoux proportional grid technique. PMID- 1439333 TI - Intraoperative brain mapping techniques in neuro-oncology. AB - Intraoperative brain mapping techniques are utilized in neuro-oncology to maximize the extent of tumor resection and seizure control, and minimize the operative morbidity. Direct stimulation mapping of the cortex and subcortical descending motor pathways will localize the rolandic cortex, dominant language speech zones and motor tracts in the internal capsule, cerebral peduncle and corticospinal tract/anterior horn cells. Electrocorticography identifies epileptogenic areas that histologically are distinctly devoid of neoplastic infiltration. Seizure control is maximal when seizure foci are resected in addition to the tumor nidus. PMID- 1439334 TI - Corticoamygdalectomy in memory-impaired patients. AB - Sixty-seven patients who underwent resection of the amygdala and temporal neocortex for intractable temporal lobe epilepsy were analyzed. Forty-four of them failed memory tests during the intracarotid sodium amytal procedure or showed severe impairment of contralateral material specific memory. Surgical outcome ratings were seizure-free or rare seizure, 51%; worthwhile improvement, 15%; failure, 34%. The least successful outcome was noted in the group with mandatory corticoamygdalectomy and seizure origin in the dominant hemisphere. There was no postoperative exacerbation of memory deficit, whether preoperative memory was normal or impaired. When hippocampal resection is inadvisable, corticoamygdalectomy may be considered. PMID- 1439335 TI - Surgery of central sensory motor and dorsolateral frontal lobe seizures. AB - Ten patients who presented with dorsolateral or frontocentral seizures were studied with chronic subdural grid electrodes. Cortical mapping, sensory-evoked potentials and chronic electrocorticography were obtained for each patient. Seizures were classified as focal, regional or dipolar. At the time of explanation, a selective functional corticectomy was performed. Surgical outcome is presented at a mean follow-up of 36 months. Two patients are seizure-free and 7 patients had a significant reduction in seizure frequency. One patient had no change in seizure pattern. Dorsolateral frontal lobe seizures have a focal functional anatomy and can be surgically treated by selective cortectomy. PMID- 1439336 TI - Surgical outcome in computer-assisted stereotactic resection of intra-axial cerebral lesions for partial epilepsy. AB - A retrospective analysis was performed in 30 patients who underwent computer assisted stereotactic resection of intra-axial mass lesions with intractable partial epilepsy. Mean follow-up was 4.1 years (2-5.5), mean age 21 years (3-45) and mean duration of seizures 8.4 years (1-26). Pathology consisted of vascular malformations in 11, glial neoplasms in 11, cortical dysplasia in 4 and gliosis in 3, and no diagnostic abnormality was found in 2 patients. The location of the lesions in some cases may have precluded a standard craniotomy and cortical resection, e.g. precentral gyrus (5), post-central gyrus (5) and deep-seated left posterior temporal region (4). Operative morbidity involved 3 patients who developed motor or language deficits. Four patients were lost to follow-up. Thirteen patients out of 26 (50%) were class I, 3 (12%) were class II, 4 (15%) were class III and 6 (23%) were class IV. These findings suggest that stereotactic lesion resection in selected cases (e.g. where lesions are located in eloquent brain regions) can be useful in providing a histological diagnosis of the epileptogenic foci and result in a favorable reduction in seizure activity without the need for a standard cortical resection. PMID- 1439337 TI - Focal encephalitis as an etiology of temporal lobe epilepsy. PMID- 1439338 TI - Use of the callosal grid system for the preoperative identification of the central sulcus. AB - The callosal grid system based on modern imaging techniques facilitates the identification of the central sulcus by its relationship to the midcallosal plane. Imaging with or without the stereotactic frame allows precise localization of various anatomic sites, which can be compartmentalized within subdivisions of the grid system. The information gained permits accurate preoperative planning and intraoperative recognition of the central sulcus and adjacent neurovascular structures. PMID- 1439339 TI - Comparison of CT- versus MRI-guided, computer-assisted depth electrode implantation. AB - Fourteen candidates for ablative seizure surgery underwent CT-guided, computer assisted stereotactic depth electrode implantation and 21 underwent MRI-guided, computer-assisted implantation. A hand-held computer with no graphic capability was used for CT-guided procedures. A computer work station which included a high resolution color graphics terminal with touchscreen interfacing and software capable of simulating targets and trajectories in single or multiple views was used for MRI-guided procedures. Previous phantom studies done with a 1.5-tesla MR scanner suggested acceptable localization error. Localizing information was obtained in 10 (71.4%) of 14 of the CT-guided implants and in 16 (76.2%) of 21 of MRI-guided cases. In the CT group, 7 (70%) were seizure-free and 8 (80%) were greater than 90% improved at 1 year follow-up. In the MRI group, 8 (80%) were seizure-free and 9 (90%) were greater than 90% improved at latest follow-up. PMID- 1439340 TI - Surgical therapy of temporal lobe seizures. AB - Resection of epileptogenic lesions and pathological studies were performed in all 35 patients with temporal lobe epilepsy, 20 male and 15 female. Their ages ranged from 6 to 48 years with an average of 22 years. Various examinations including CT scan were carried out without any positive finding. EEG showed spike formation in the temporal lobes in all 35 patients. Epilepsy lesions were removed from the right temporal lobe in 22 patients and from the left temporal lobe in 13 patients. Pathological changes were found in all epilepsy lesions by light and electron microscopy. The operative outcomes were seizure-free since discharge in 10 patients (28.5%), seizure-free after some early attacks (34.2%) in 12 patients, seizure-free for 2 or more years and then rare or occasional attacks in 6 patients (17.1%), marked reduction of seizures in 5 patients (14.5%) and moderate or less reduction of seizure tendency in 2 patients (5.7%), with an effective rate of 93%. No death or severe complications did occur. PMID- 1439341 TI - Cerebellar stimulation for seizure control: 17-year study. AB - Since 1974, 32 seizure patients have undergone chronic cerebellar stimulation (CCS); 27 have been contacted with 9 (7 spastic, 2 epileptic) continuing to use CCS for an average of 14.3 years (10-17 years). 6 (67%) are seizure-free and 3 (33%) have a reduction of seizure frequency. In the last 2 years, 2 other patients with spastic seizures, who were using CCS for 13 years, died of respiratory illness; 1 had been seizure-free and the other had a reduction. Of the remaining 16 patients (12 spastic, 4 epileptic) who did use CCS for an average of 8.3 years (2-14 years) and now have nonfunctioning stimulators, 5 (31%) continue to be seizure-free, 7 (44%) have a reduction and 4 (25%) have no change or a slight increase. Overall, 23 (85%) patients have benefitted from CCS. Stimulation charge densities were 0.9-2.5 microC/cm2/phase delivered at 10-180 pulses/sec to bilateral electrode pads on the superomedial cerebellar cortex. CCS is relatively safe and nonablative, and could be offered for patients with intractable seizures originating from bilateral or extratemporal foci. PMID- 1439342 TI - Stereotactic thalamotomy for medically intractable essential tremor. AB - Objective surgical symptomatic outcome of ventrolateral (VL) thalamotomy specifically for essential tremor is uncommonly reported and functional outcome has not been investigated previously. In the present series, 7 patients underwent unilateral and 1 patient staged bilateral VL thalamotomies for disabling medically refractory essential tremor. At follow-up examination (mean 17.3 months, range 1-50 months), all patients enjoyed complete ablation or significant amelioration of the targeted tremor. Disability as determined by a modified form of an established rating scale for tremor was reduced from moderate (57%) or severe (43%) to absent (86%) or mild (14%). Interestingly, voice tremor was ablated or significantly improved in 71.4% of patients with preoperative voice tremor. PMID- 1439343 TI - Ventral intermediate thalamotomy for posttraumatic hemiballismus. AB - An unusual case of hemiballismus following closed head injury is presented. The abnormal movement persisted for 16 years despite medical treatment. Preoperative studies did not reveal a specific lesion within the subthalamic nucleus or within the basal ganglia. A stereotactic ventral intermediate thalamotomy was performed producing a complete resolution of the ballistic movement which persisted for the length of our 12-month follow-up. PMID- 1439344 TI - Neurosurgical treatment of spasticity: selective posterior rhizotomy and intrathecal baclofen. AB - The pathophysiology of spasticity and the history of posterior rhizotomies are reviewed. The rationale for selective posterior rhizotomies is that electrical stimulation identifies afferent posterior rootlets that terminate on relatively uninhibited alpha motoneurons; if these uninhibited rootlets are divided, spasticity can be alleviated without loss of other posterior root functions. Indications, technique, and results of selective posterior rhizotomies are presented. The use of continuous intrathecal baclofen (CITB) is summarized. CITB at doses of approximately 300 micrograms/day consistently reduces lower extremity spasticity and diminishes or alleviates muscle spasms in adults with spasticity of spinal origin. Single doses of intrathecal baclofen significantly decrease lower extremity muscle tone in children with cerebral palsy, and the effects can be maintained in these patients by CITB infusions which diminish muscle tone not only in the lower extremities, but in the upper extremities as well. CITB is best accomplished via an externally programmable pump that allows titration of the daily dose to attain the desired reduction in spasticity. Factors influencing the decision for rhizotomy or CITB are presented. PMID- 1439345 TI - Magnetic resonance imaging and anatomic atlas mapping for thalamotomy. AB - A computerized anatomic atlas mapping technique has been developed and used to determine target sites for stereotactic thalamotomies. The digitized stereotactic atlases of Schaltenbrand and Bailey, Van Buren and Borke, and Schaltenbrand and Wahren are used in conjunction with an associated electrophysiological data base to determine the intended target site on MR images of the diencephalon. This mapping technique uses the 'Brierley and Beck' proportional hypothesis for thalamic nuclear determination. Target site determination by this method was found to be very accurate, and frequently the mere placement of the probe in the target site resulted in tremor cessation. PMID- 1439346 TI - Application of magnetic resonance imaging in functional stereotactic thalamotomy for the evaluation of individual variations of the thalamus. AB - An application of MRI in functional stereotactic thalamotomy is presented. To estimate the individual anatomic variations of the thalamus prior to stereotactic thalamotomy, a special study using a proton density image that shows myeloarchitectonic features of the thalamus was performed. The proton density MRI was demonstrated to be very useful to determine the safest trajectory and tentative target point. However, as a detailed functional localization of the thalamic subnuclei cannot be yet obtained by MRI, the final target should be decided on the basis of electrophysiological findings. PMID- 1439347 TI - Neurophysiological atlas created by mapping of clinical responses elicited on electrical stimulation of the human thalamus. AB - By computer processing of intraoperative neurophysiological data and intraoperative X-ray films, and using a 0.5-mm-step three-dimensional atlas created by interpolation of Schaltenbrand-Bailey's atlas, a neurophysiological atlas based on clinical responses upon electrical stimulation of the subcortical structures of patients who underwent stereotactic surgery in the awake state was created. There was considerable overlap in the distribution of motor and sensory responses in the vicinity of the ventral intermediate (VIM) thalamus: however, motor responses, particularly irregular movements, tended to be confined within the VIM and ventro-oralis posterior (VOP), whereas sensory responses tended to be localized in the VIM and ventroposterolateral nuclei, with considerable extension into the ventroposterior subthalamic region. In either motor or sensory responses, no definite somatotopic pattern could be determined. PMID- 1439348 TI - A new multimodality correlative imaging technique for VOP/VIM (VL) thalamotomy procedures. AB - This paper describes our experience at Mayo Clinic with a new technique for planning ventro-oralis posterior (VOP) ventral intermediate (ventrolateral) VIM (VL) thalamotomy procedures for selected patients with medically intractable tremor. This new method employs a multimodality correlative imaging technique for determining the lesion target point on MR images. At surgery, stereotactic frame settings for the final lesion target were ultimately determined by stereotactic ventriculography modified by neurophysiological recording. Acceptable correlation was found between the multimodality correlative imaging method and the actual target coordinates determined by ventriculography and semi-microelectrode recording. PMID- 1439349 TI - Spinal cord stimulation for multiple sclerosis: quantifiable benefits. AB - From 1984 to 1991, a quantitative study of 5 multiple sclerosis (MS) patients has been determining benefits from epidural (C7-T1 level) spinal cord stimulation (SCS). The 5 patients (4 male, 1 female; 4 tetraparetics, 1 hemiparetic) were 36 45 years of age having had symptoms for 12-22 years. Five quantitative tests were given prior to and during SCS on 4-8 occasions; 'off' periods were planned and also did occur when the electrode(s) broke (3 patients). With SCS, hand dynamometry showed a 2- to 4-fold increase in the 3 patients with weak hand function. Jebson Hand Time Testing showed a rapidity improvement to 1/2-1/7 of time in the same 3 patients. Minnesota Manipulation Testing with SCS was improved to 1/3-1/2 of time in 2 of these 3 patients tested. Manual muscle strength increased in all patients by 20-50% in 'normal range'. Ambulation in the parallel bars increased with SCS in 2 of the 4 wheelchair patients, while the hemiparetic patient could walk without his cane. All patients showed varying quantifiable improvements with SCS, but over the duration of testing the patients slowly deteriorated. SCS is a rehabilitation option for the weakened MS patient, to be used earlier rather than later in the deterioration of MS patients. PMID- 1439350 TI - Dorsal selective rhizotomy through a limited exposure of the cauda equina at L1. PMID- 1439351 TI - Pioneers of stereotactic neurosurgery. AB - The beginnings of stereotactic and functional neurosurgery can be traced as far back as 1873 when Dittmar reported the use of a guiding device for the placement of probes into the medulla oblongata in animals. Further pioneering work was done by Zernov and Altukhov in Russia (1889), Clarke and Horsley in England (1908), and Spiegel and Wycis in the United States (1947), as well as others. After a promising initiation, interest in stereotactic neurosurgery waned after the introduction of L-dopa in the 1960s. Later, the introduction and incorporation of new imaging technology into stereotactic techniques signaled the rebirth of stereotactic and functional neurosurgery as a versatile and exciting subspecialty not only in the resection of previously unresectable lesions but also in the functional restoration of central nervous system function. This brief paper will focus on the personalities that have pioneered stereotactic neurosurgery over the past century. PMID- 1439352 TI - Central nervous system grafting: animal and clinical results. AB - In the 2 years since this topic was reviewed, there have been dramatic changes in our understanding of the basic science of central nervous system transplantation, as well as further realization of the crude state in which we find the clinical application of this technology. Early concepts of simple diffusion and neuronal replacement have been altered as we understand more the rule of neurotrophic factors and the response of the host to the transplantation process. Clinical studies are becoming increasingly sophisticated as we realize that the initial observations were frequently flawed and quantitative evaluations are increasingly important in determining the effectiveness of the procedure. There is, nevertheless, still a great deal of excitement in the field as new technologies are being developed and utilized in the clinical sphere. PMID- 1439353 TI - Stereotactic technique and pathophysiological mechanisms of neurotransplantation in Huntington's chorea. AB - In Huntington's chorea, embryonal brain tissue (striatum) was implanted in the caudate nucleus bilaterally, using stereotaxy assisted by CT. A special cannula allowed the placement into the brain of 3 or 4 grafts of embryonal tissue along the determined trajectory by one introduction of the cannula. The pathophysiological mechanism of neurotransplantation in Huntington's chorea is to compensate for the degenerated striatal tissue by embryonal striatum, so it is necessary to supply a quantity of embryonal striatal tissue which enables the whole functional integrity. Therefore, we use material from several embryos. PMID- 1439354 TI - Bilateral fetal grafts for Parkinson's disease: 22 months' results. AB - Five patients with severe Parkinson's disease underwent bilateral multiple graft implants of nondissociated fetal mesodiencephalic tissues. Graft implantation was performed in China following CT-guided stereotactic placement of a novel delivery system. Follow-up has demonstrated substantially reduced levodopa requirements and clinical improvements of motor, postural functions and reduction of freezing and on-off phenomenon. PET utilizing [18F]-dopa, at 14 months in the first case, suggested graft-induced restoration of dopaminergic transmission in the striatum. PMID- 1439355 TI - MR-guided ventral intermediate thalomotomy for posttraumatic hemiballismus. PMID- 1439356 TI - Excision of arteriovenous malformation in sensorimotor and language-related neocortex using stimulation mapping and corticography under local anesthesia. PMID- 1439357 TI - Computer and imaging technology's impact on stereotactic neurosurgery. A 1987 1991 update. AB - Many improvements in computer and imaging technology have occurred since the last meeting of the American Society for Stereotactic and Functional Neurosurgery in 1987. These improvements are leading to a much wider acceptance of computerization and computer-assisted surgical procedures in the stereotactic neurosurgery field. This paper surveys the current fields of computer and imaging technology and its relationship and impact on the field of stereotactic neurosurgery during the period of 1987-1991. Forecasts about future developments are also discussed. PMID- 1439358 TI - Stereotactic localization and guidance using a machine vision technique. AB - Machine vision techniques (video cameras) can be used to determine the three dimensional position of objects. This transformation can be accomplished with standard mathematical algorithms. Initial accuracy tests of stereotactic localization with video cameras were performed using a standard Brown-Roberts Wells (BRW) phantom simulator coupled with the BRW angiographic localizer. Localization accuracy was within 1.5 mm. Potential applications of machine vision techniques include freehand stereotactic localization of the position and orientation of surgical instruments. With sufficient computer speed these techniques can be used for continuous monitoring of the position of instruments within the cranial vault. PMID- 1439359 TI - Utilization of image-derived computer-assisted stereotaxis in a community-based practice setting. AB - The success of a community-based stereotactic program is dependent upon community commitment, technological capability, referral base, patient/family support and, most importantly, proper patient selection. To develop a program of superior quality requires not only a substantial financial commitment, but also a basic philosophical approach which fully supports acquisition and education of support staff, physical plant renovation and an establishment of an expanding referral base. This report details the development of a highly sophisticated stereotactic program in Cedar Rapids, Iowa, a semirural community with a base referral population of approximately 300,000. PMID- 1439360 TI - Using mark-recapture methodology to estimate the size of a population at risk for sexually transmitted diseases. AB - To study the spread of sexually transmitted diseases (STDs) using social/sexual mixing models, one must have quantitative information about sexual mixing. An unavoidable complication in gathering such information by survey is that members of the surveyed population will almost certainly have sexual contacts outside that population. The number of these outsiders may be substantial and, hence, important for the modelling process. In this paper, we develop a mark-recapture model for estimating the size of the population at risk for contracting a STD due to direct sexual contact with a specified population targeted by a survey. This mark-recapture methodology provides a reliable method of estimating the number of outsiders. Because not everyone in the targeted population may be sexually active, the size of the sexually active subset, used as the number marked in our tag-recapture formulation, must be estimated, which introduces extra variability. We derive an estimator of the variance of the estimated total number at risk that accounts for this extra variability and an expression for the bias of that estimator. We extend the methodology to stratified surveys and illustrate its use with data collected from a population of university undergraduates to estimate sexual mixing parameters of a deterministic model of the spread of STDs. PMID- 1439361 TI - Effects of mid-point imputation on the analysis of doubly censored data. AB - Doubly censored data arise in some cohort studies of the AIDS incubation period because the time of infection may be known only up to an interval defined by two successive screening tests for HIV antibody. A simple analytic approach is to impute the infection time by the mid-point of the interval and then apply standard survival techniques for right censored data. The objective of this paper is to investigate the statistical properties of such a mid-point imputation approach. We investigated the asymptotic bias of the Kaplan-Meier estimate, coverage probabilities of associated confidence intervals, bias in hazard ratio, and the size of the logrank test. We show that the statistical properties of mid point imputation depend strongly on the underlying distributions of infection times and the incubation periods, and the width of the interval between screening tests. In the absence of treatment, the median incubation period of HIV infection is approximately 10 years, and we conclude that, for this situation, mid-point imputation is a reasonable procedure for interval widths of 2 years or less. PMID- 1439362 TI - Calculating the prevalence of cancer. AB - Incidence, prevalence and mortality are commonly used measures to assess the impact of disease on human populations. Prevalence, although regularly assessed for a number of different diseases, has only had recent use to measure the impact of cancer. The calculation of the prevalence of cancer presents several difficulties since there is no reporting mechanism established to measure the proportion of the community that has the disease. In the absence of such a mechanism, mortality data linked to incidence data from cancer registries have been used. The assumption is made that once diagnosed with cancer an individual remains a prevalent case until death. In this paper we present alternatives to this assumption and use them to produce estimates of cancer prevalence. We illustrate the effect of these assumptions on the calculated prevalence of cancer using data from the British Columbia Cancer Registry. PMID- 1439363 TI - Estimation of a common risk ratio in stratified case-cohort studies. AB - The case-cohort study design is a useful modification of the case-control design, which allows direct estimation of the risk ratio without the rare-disease assumption. While several risk ratio estimation procedures have been proposed under large-strata settings, only the Mantel-Haenszel point estimator is available in sparse stratifications. This paper provides simple confidence limits methods, based on the large-sample distribution of the Mantel-Haenszel risk ratio, that apply to both large-strata and sparse-data situations. For the Tarone risk ratio, I give a new large-strata variance estimate. PMID- 1439364 TI - Correlated binomial variates: properties of estimator of intraclass correlation and its effect on sample size calculation. AB - In group randomized studies, the sample size calculations are complicated by within group (worksite, community, etc.) correlation. We compare by simulation the moment method and the more standard ANOVA method of estimating the intraclass correlation. We find the former is less biased for a small to moderate number of clusters but the difference disappears when the appropriate degree of freedom is used for the ANOVA estimator. We propose a simulation approach for sample size determination and illustrate it with an example. PMID- 1439365 TI - A note on last case influence using the partial likelihood approach under heavy censoring. AB - The Cox proportional hazards model always treats the last observation in a time ordered data set as an inexact survival time. In certain situations this can lead to this observation always having a low case influence and consequently never being highlighted by a case influence analysis. Thus an influential value can become non-influential by a miscalculation of survival time and this, in turn, can affect conclusions of an analysis based on statistical significance (P values). PMID- 1439366 TI - Bayesian methods for prevalence estimates from incomplete administrative lists. PMID- 1439367 TI - Adjusting for baseline: change or percentage change. PMID- 1439368 TI - Caregiving demands: their difficulty and effects on the well-being of elderly caregivers. AB - Nurses assess situations involving elderly caregivers, yet data conflict on how caregivers perceive caregiving demands. To develop appropriate research-based interventions, more data are needed on specific aspects of these demands. Discussed are data from interviews with 60 elderly caregivers regarding tasks and personal demands. Results suggest that personal demands are perceived as more difficult than task demands and are associated to a greater extent with caregiver life satisfaction and depression. Issues are raised, however, regarding the measurement of expressed difficulty. Findings also support the adaptive capacity of these caregivers and their commitment to the caregiving role. Implications for nursing practice and nursing science are discussed. PMID- 1439369 TI - Maternal role satisfaction: a new approach to assessing parenting. AB - There is a need to study the maternal role beyond the child's first year of life. This investigation, using a framework of Locke's expectancy theory, describes the expectations, surprises, values, and satisfactions experienced by 102 mothers of teens. Content analysis of written narratives describing surprises encountered by these mothers is also presented. Data were collected by questionnaire. Findings offer support for Locke's theory in two ways: (1) expectation for role was less important than value attainment in predicting the level of maternal role satisfaction, and (2) encountering at least one positive surprise was associated with a higher level of maternal role satisfaction. These variables are offered as a useful nursing approach to the assessment of the parenting experience. Knowledge of the satisfactions reported may be encouraging to mothers anticipating this stage of life. PMID- 1439370 TI - Caring, virtue theory, and a foundation for nursing ethics. AB - The purpose of this paper is to critically examine the use of a framework of virtue theory as a foundation for a nursing ethic embodied in the caring ideal. The first section summarizes the problems identified with traditional moral theory as a foundation for a nursing ethic based on the caring ideal. From these problems, adequacy conditions that a foundation must meet are identified. In section two, the basic ideas of virtue theory are sketched and an account of how virtue theory can be used as a foundation for a nursing ethic based on the caring ideal is discussed. Finally, virtue theory as a foundation for a nursing ethic a la caring is assessed against the adequacy conditions delineated in section one. The conclusion of this paper is that virtue theory does not offer a viable alternative to duty-based theories. While virtue theory provides promise in meeting the identified adequacy conditions, serious secondary issues arise that can not be immediately nor easily resolved. PMID- 1439371 TI - Physiological nursing research in dyspnea: a paradigm shift and a metaparadigm exemplar. AB - Dyspnea, the primary activity-limiting symptom in chronic obstructive pulmonary disease, is associated with respiratory muscle mechanisms. This leads to a paradigm shift from pulmonary processes to respiratory muscle function. Within the context of an integrative metaparadigm, basic and clinical nursing science are developed: to better understand physiological processes associated with dyspnea as presented in three physiological models of dyspnea, to identify respiratory muscle mechanisms associated with current treatment strategies for dyspnea, to eventuate clinical assessments of exercise endurance, and to generate treatment strategies in the promotion of positive life processes. The basic knowledge developed within this program provides a foundation for the generation of strategies to assess patients, to promote normal functioning of life processes, and to enhance positive coping with responses to illness. Thus, this research program provides a model for the development of substantive physiological and clinical knowledge for nursing practice. PMID- 1439372 TI - The 1990s will place great emphasis on the quality of higher education. PMID- 1439373 TI - Evaluation of a Swedish version of the Arthritis Self-Efficacy Scale. AB - There is a great need today for clinically useful instruments in the rehabilitation of chronic pain patients. The Arthritis Self-efficacy Scale measures patients' perceived self-efficacy to cope with the consequences of chronic arthritis. The aim of the present study was to evaluate a Swedish version of the Arthritis Self-efficacy Scale with respect to factor structure and reliability. Twenty-five chronic pain patients and twenty-four rheumatology patients were given a Swedish version of the Arthritis Self-efficacy Scale twice within a three week interval. The three factor structure of the scale was confirmed; Cronbach's alpha for internal consistency ranged between 0.82-0.91 and test-retest correlations ranged between 0.81-0.91, showing that the instrument satisfactorily met psychometric standards. PMID- 1439374 TI - Basis of the quality of nursing care. A short quantitative description. AB - The purpose of the study is to create a descriptive evaluation basis for the quality of nursing care. In this article a short quantitative description of the most frequent elements of good nursing care is reported, using the views of Finnish nurses and nurse teachers. These elements are: interaction, comprehensiveness, need-centerness, initiativeness, technical procedures and knowledge-base. Based on these, further research areas can be seen both in nursing practice and in education. PMID- 1439375 TI - The condition of the oral mucosa in institutionalized elderly patients before and after using a mucin-containing saliva substitute. AB - The purpose of this investigation was to evaluate whether the condition of the oral mucous membrane and the mouth comfort of the elderly could improve using a mucin-containing saliva substitute. In total, 52 patients were examined before and after a 60-day treatment period, with mucin-containing saliva substitute given three times a day before meals. The patients were examined with regard to weight, oral mucosa condition, the duration of meals, eating and swallowing. Before the treatment period the prevalence of stomatitis was 90.4% and oral candidosis was 80.8% compared to 15.4% and 5.8% respectively after the treatment period. The pH increased significantly. Artificial mucin-containing saliva substitute seems to be an adequate treatment of stomatitis and oral candidosis in elderly patients. PMID- 1439377 TI - Translation of an instrument. The US-Nordic Family Dynamics Nursing Research Project. AB - Translation of a research instrument questionnaire from English to another language is analyzed in relation to principles involved, procedures followed, and problems confronted by nurse researchers from the US-Nordic Family Dynamics Nursing Research Project. Of paramount importance in translation are translation equivalency, congruent value orientation, and careful use of colloquialisms. It is important to recognize that copyright guidelines apply in the translation of an instrument. Approaches to solving instrument translation problems are discussed. PMID- 1439376 TI - Greek fathers' participation in labour and care of the infant. AB - Greek fathers' (n = 157) reactions to their presence at the delivery, their expectations about the baby and their childcare practices were explored at the 4th-6th week postpartum. Only 10% of the sample attended the delivery. Their non attendance was attributed, by the greatest number of fathers, to official hospital policy while the rest claimed it was entirely their decision. Half of the non-attenders expressed the desire to have been present while a large percentage of mothers were said to have wanted them to be present. The small number of fathers who attended the birth felt strong and satisfied. In respect to early fatherhood, three main themes were explored: reaction to fatherhood, enjoyment of the child and involvement in childcare. All three dimensions were strongly correlated. PMID- 1439378 TI - The sense of coherence concept and its relation to personality traits in Swedish samples. AB - The paper proposes that Antonovsky's salutogenic orientation and his sense of coherence (SOC) concept provide a sound theoretical basis for the study and strengthening of the caring component in clinical practice. In order to study the operational utility of the concept, the 29-item SOC questionnaire (in two formats) was administered to five Swedish samples (3 groups of nurses, patients in a hospital emergency department, and a general population sample). Psychometric data are provided which test the internal and test-retest reliability of the SOC scale. A Self-Motivation Inventory (SMI) and the Karolinska Scales of Personality (KSP) were used to test the relation between the SOC concept and personality traits. The results revealed that those with strong SOC also scored as having more general motivation and less Somatic and Psychic Anxiety as well as less Hostility. In addition the data, though in some part modest in sample size, consistently supported the view that the SOC scale is a robust instrument. Particular note is taken of its crosscultural character and of its potential utility in clinical work. PMID- 1439379 TI - Theory and methods for research on ethical issues in dementia care. AB - Swedish research on ethical issues in dementia care is almost exclusively done by nursing scientists. Many of these studies are rightfully acclaimed as exemplary research. But the strong focusing on the nurse and her relation to the patient tends to bias the ethical issues--the attitudes of other persons involved or affected are also in need of investigation. Further, there is a predilection for content analysis at the expense of causal analysis. In this paper an eclectic approach to the study of ethical issues in dementia care is advocated. More interdisciplinary communication and co-operation is also needed--especially between nursing scientists and moral philosophers. To facilitate such communication and co-operation a model for analysis of ethical issues is presented and discussed. To illustrate my ideas I use three articles by researchers from the department of advanced nursing in Umea: Ekman & Norberg (1988), Norberg & Asplund (1990) and Akerlund & Norberg (1989-90). PMID- 1439380 TI - Relaxation training as an integral part of caring activities for cancer patients: effects on wellbeing. AB - The purposes of this study were twofold. The first was to investigate if relaxation training conducted by nurses as an integral part of their caring activities affected breast cancer patients' experiences of radiotherapy sessions as well as their general wellbeing. Second was to evaluate a pedagogical model for large scale application of relaxation training as an integral part of caring. The sample consisted of 64 consecutive outpatients with breast cancer at a Swedish oncology clinic, receiving their first radiotherapy treatment course following surgery. Every second patient was assigned to an experimental group (n = 32, mean age: 59.5 years) and every other second patient was assigned to a control group (n = 32, mean age: 60.0 years). The programme resulted in the following general effects: fewer perceived daily hassles and a more cheerful overall mood state. The following treatment situation specific effects were noted: programme participants appraised the treatment sessions as successively more benign-positive and less threatening. They also reported more perceived muscular tensions during treatment sessions. Most goals concerning the routinization of the pedagogical model were reached. PMID- 1439381 TI - Determination of perceived health among elderly coronary patients. PMID- 1439382 TI - [The temporomandibular joint]. AB - With its discordant articular surfaces and complete division in two cavities separated by a disk, the temporomandibular joint appears as a complex anatomical and functional entity. Combined movements involving anteroposterior gliding between the disk and temporal bone in the upper cavity, anteroposterior condyle translation, hinge and rotation movements between the disk and mandibular condyle contribute to the different movements of the jaw. With dental occlusion, the masticatory apparatus therefore includes five functionally coordinated articular compartments. Various impairments of the normal static and dynamic features of the temporomandibular joint may lead to relatively frequent pathological conditions which can be easily diagnosed by modern imaging and arthroscopic methods. PMID- 1439383 TI - [Minimal hemorrhagic diathesis]. PMID- 1439384 TI - [The 3d sound following coronary bypass]. PMID- 1439385 TI - [Systemic lupus erythematosus]. PMID- 1439386 TI - [Tuberculous pericarditis: value of adenosine deaminase activity level assessment]. PMID- 1439387 TI - [Preventive medical treatment of kidney stones]. PMID- 1439388 TI - [Smell. Physiology--its assessment--its disorders in head injuries]. PMID- 1439389 TI - [Medical terminology]. PMID- 1439390 TI - Lower extremity injury. Biomechanical factors associated with chronic injury to the lower extremity. PMID- 1439391 TI - Gastrointestinal problems related to endurance event training. PMID- 1439392 TI - Cardiac rehabilitation programmes in children. PMID- 1439394 TI - Reproduction for the athletic woman. New understandings of physiology and management. AB - A physically active and athletic lifestyle is not only a healthy but a fulfilling choice for women. Although there is extensive literature on 'athletic amenorrhoea' which implies that exercise causes loss of the menstrual cycle, there is inadequate scientific evidence for a causal relationship. The reproductive system adapts to environmental, nutritional, emotional and physical stressors or 'threats' by downward adjustment towards the premenarcheal pattern. The hormonal milieu of this adaptation is low gonadal steroid and high glucocorticoid levels which synergistically increase the risk for a negative bone balance. Athletic women may become amenorrhoeic if reproductive immaturity, emotional stress and undernutrition coexist with increasing exercise loads. Treatment for athletic women with menstrual cycle changes requires that hypothalamic stressors be identified and decreased. In addition, as progesterone deficiency (from disorders of ovulation, whether flow is regular or absent) is the most prevalent menstrual cycle change, treatment with medroxyprogesterone on days 16 to 25 of their cycle will not only provide regular flow (if estrogen levels are sufficient) but will also promote increased bone density. PMID- 1439393 TI - Exercise training in obese diabetic patients. Special considerations. AB - The relationship between obesity and type II diabetes mellitus is well established and a majority of type II diabetic individuals are classified as obese. The pathogenesis of type II diabetes mellitus is not fully understood; however, multiple organ systems are involved, including abnormalities of insulin secretion, peripheral insulin resistance and hepatic insulin resistance. The goal of the treatment for the obese diabetic is to normalise these alterations and achieve normoglycaemia. Traditionally, the initial therapy, aiming to accomplish weight reduction, is diet and exercise. In obese type II diabetic patients, the whole body insulin-dose response curve is markedly depressed. A single exercise session improves and partially normalises both insulin responsiveness and sensitivity for glucose utilisation. Furthermore, a single bout of physical activity often results in decreased plasma glucose levels, which persists into the postoperative period. Type II diabetes patients participating in regular exercise programmes can potentially improve their metabolic control. An improved glucose control in both lean and obese type II diabetic patients under the age of 55 years has been demonstrated by improved HbA1C levels and glucose tolerance tests following physical training programmes. The effect of regular exercise on the metabolic control in these younger patients does not appear to be correlated with weight reduction. For most type II diabetic men over 55 years of age, physical training is not a feasible form of therapy because of other interfering diseases which may complicate or severely hinder all physical training apart from very low intensity exercise programmes. Lean, older, type II diabetic patients who have been able to exercise for 10 weeks or up to 2 years demonstrate no change in HbA1C levels, glucose tolerance or bodyweight. Thus, there is a clear difference in metabolic response to regular exercise between younger and older type II diabetic patients. The younger patient appears to be more inclined to respond to physical training with improvements in the metabolic control. The reason for this apparent difference is not clear, but possible explanations may include differences in training intensity, the presence or degree of complicating diseases, pretraining level of metabolic control or bodyweight. Type II diabetics are predisposed to cardiovascular disease and are characterised by hyperlipidaemia. In obese type II diabetic individuals, physical training improves the blood lipid profile as measured by decreased levels of triglycerides and total cholesterol. In young, overweight diabetics, improved lipid profiles can be achieved despite no change in bodyweight, while no apparent effects are reported for lean patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1439395 TI - Head and neck injuries in soccer. Impact of minor trauma. AB - Head injuries have been shown to account for between 4 and 22% of soccer injuries. Clinical and neuropsychological investigations of patients with minor head trauma have revealed organic brain damage. 69 active football (soccer) players and 37 former players of the Norwegian national team were included in a neurological and electroencephalographic (EEG) study to investigate the incidence of head injuries mainly caused by heading the ball. 3% of the active and 30% of the former players complained of permanent problems such as headache, dizziness, irritability, impaired memory and neck pain. 35% of the active and 32% of former players had from slightly abnormal to abnormal EEG compared with 13 and 11% of matched controls, respectively. There were fewer definitely abnormal EEG changes among typical 'headers' (10%) than among 'nonheaders' (27%). The former players were also subjected to cerebral computed tomography (CT), a neuropsychological examination and a radiological examination of the cervical spine. One-third of the players were found to have central cerebral atrophy and 81% to have from mild to severe (mostly mild to moderate) neuropsychological impairment. The radiological examination of the cervical spine revealed a significantly higher incidence and degree of degenerative changes than in a matched control group. PMID- 1439396 TI - Strength, flexibility and athletic injuries. PMID- 1439397 TI - High-altitude training. Aspects of haematological adaptation. AB - Physical training at high altitude improves performance at high altitude. However, studies assessing performance improvements at sea level after training at higher altitudes have produced ambiguous and inconclusive results. Hypoxia induced secondary polycythemia is a major contributor to increased work capacity at altitude. The common finding upon exposure to hypoxia is a transient increase in haemoglobin concentration and haematocrit because of a rapid decrease in plasma volume followed by an increase in erythropoiesis per se. Both nonathletes and elite endurance athletes have maximal reticulocytosis after about 8 to 10 days at moderate altitude. Training periods of 3 weeks at moderate altitudes result in individual increase of haemoglobin concentration of about 1 to 4%. A more accentuated increase in haemoglobin can be obtained with longer sojourns at moderate altitude. The normal erythropoietin reaction upon exposure to hypoxia comprises initially increased levels followed by a decrease after about 1 week. Thus, the maintenance of a high erythropoietin concentration is not a prerequisite for a sustained increase in erythrocyte formation at high altitude. The main pharmacological modulator of erythropoietin production seems to be adenosine. But modulators such as growth hormone and catecholamines may also potentiate the effect of hypoxia per se on erythropoietin production. On the other hand, there is a risk that the stress hormones may induce a relative depression of the bone marrow particularly in the early phase of altitude training when the adaptation is minimal and the stress reaction is most accentuated. The most important 'erythropoiesis-specific' nutrition factor is iron availability which can modulate erythropoiesis over a wide range in humans. Adequate iron stores are a necessity for haematological adaptation to hypoxia. However, at moderate altitude, there is a need for rapid mobilisation of iron and even if the stores are normal there is a risk that they cannot be mobilised fast enough for an optimal synthesis of haemoglobin. Data from healthy athletes training at moderate altitudes suggest a true increase in haemoglobin concentration of about 1% per week. Complete haematological adaptation occurred when sea level residents have similar haemoglobin concentrations at moderate altitude compared with residents. The normal difference in haemoglobin concentrations can be estimated to be about 12% between permanent residents at sea level and at 2500m above sea level. This difference indicates a necessary adaptation time of about 12 weeks. If the training period at moderate altitude must be shorter, several sojourns at short intervals are recommended. The important factor in haematological adaptation in athletes at moderate altitude is hypoxia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1439398 TI - Exercise training for patients with coronary artery disease. Cardiac rehabilitation revisited. AB - Medically prescribed and supervised physical activity forms the keystone for cardiac rehabilitation. A patient's potential and limitations for successful participation in an active restoration programme are determined by the degree of symptomatic recovery and physiological adaptations to a standardised, multistage exercise test. Confirmation of the effects of physical activity intervention is measured by the performance of the same exercise test under near identical conditions at periodic intervals. The prescribed physical activity regimen is usually performed minimally 3 times per week in sessions which last from 30 to 60 minutes. The object is to utilise from 100 to 200 kcal per exercise session. The demonstrated benefits of regular physical activity include reduction of the systolic blood pressure and heart rate at supine rest and while performing submaximal work, an increased level of physical work capacity, reduction in the myocardial oxygen cost at rest and during performance of submaximal exercise, reduction in percentage body fat with a concomitant increase in muscle mass, and reduction in plasma triglycerides. Regular physical activity, in and of itself, does not effect a reduction in plasma cholesterol or an increase in high density lipoprotein cholesterol, nor does it affect such lifestyle habits as cigarette smoking and alcohol consumption. While contraindications to performing medically prescribed and supervised physical activity are usually restricted to the physically incapacitated patient, failure to achieve an exercise threshold for systolic blood pressure of 140mm Hg or higher is probably a contraindication. This conclusion is based on findings which indicate that treated and control patients with this physiological limitation experience the same mortality rates over 3 years. Regularly performed physical activity by coronary artery diseased patients is associated with reductions in mortality from all cardiovascular causes except sudden death. This intervention does not effect morbidity. Although the scientific evidence warrants the prudent use of physical activity for coronary artery disease patients, the case for its long term benefits remains to be proved. PMID- 1439399 TI - Running injuries. A review of the epidemiological literature. AB - Running is one of the most popular leisure sports activities. Next to its beneficial health effects, negative side effects in terms of sports injuries should also be recognised. Given the limitations of the studies it appears that for the average recreational runner, who is steadily training and who participates in a long distance run every now and then, the overall yearly incidence rate for running injuries varies between 37 and 56%. Depending on the specificity of the group of runners concerned (competitive athletes; average recreational joggers; boys and girls) and on different circumstances these rates vary. If incidence is calculated according to exposure of running time the incidence reported in the literature varies from 2.5 to 12.1 injuries per 1000 hours of running. Most running injuries are lower extremity injuries, with a predominance for the knee. About 50 to 75% of all running injuries appear to be overuse injuries due to the constant repetition of the same movement. Recurrence of running injuries is reported in 20 to 70% of the cases. From the epidemiological studies it can be concluded that running injuries lead to a reduction of training or training cessation in about 30 to 90% of all injuries, about 20 to 70% of all injuries lead to medical consultation or medical treatment and 0 to 5% result in absence from work. Aetiological factors associated with running injuries include previous injury, lack of running experience, running to compete and excessive weekly running distance. The association between running injuries and factors such as warm-up and stretching exercises, body height, malalignment, muscular imbalance, restricted range of motion, running frequency, level of performance, stability of running pattern, shoes and inshoe orthoses and running on 1 side of the road remains unclear or is backed by contradicting or scarce research findings. Significantly not associated with running injuries seem age, gender, body mass index, running hills, running on hard surfaces, participation in other sports, time of the year and time of the day. The prevention of sports injuries should focus on changes of behaviour by health education. Health education on running injuries should primarily focus on the importance of complete rehabilitation and the early recognition of symptoms of overuse, and on the provision of training guidelines. PMID- 1439401 TI - [What is your roentgen diagnosis? Hepatodiaphragmatic interposition of the right colonic flexure, Chilaiditi syndrome in dolichocolon]. PMID- 1439400 TI - Stress fractures in the athlete. Diagnosis and management. AB - Stress fractures can be a troublesome injury for the sports medicine clinician. The first description was in military personnel, but recently there is an increasing awareness and diagnosis of stress fractures in the athletic population. Stress fractures have been described in all extremities. Some fractures appear to have a degree of sports specificity. Bone is a dynamic tissue which strengthens and remodels in response to stress. Maladaptation to stress causes osteoclastic activity to supersede osteoblastic activity, thereby allowing weakening of the bone. These areas of weakening may fracture and create prodromal symptoms and clinical findings. Localised pains of insidious onset which are activity related are the hallmarks in the clinical history. The physical examination can exhibit localised tenderness, redness and swelling. Radiographs can be negative for up to 4 months. The gold standard for diagnosis is the triple phase 99mtechnetium bone scan. The treatment of a stress fracture is usually conservative. Very few cases require surgical management. The algorithm of conservative management includes: rest, appropriate education for treatment and preventive care, analgesics, serial radiographs, icing and physical therapy modalities, appropriate exercise to prevent detraining, rehabilitation and a regimented return to participation and competition. PMID- 1439402 TI - [Endosonography: progress in the diagnosis of endocrine pancreatic tumors]. AB - Diagnostic procedures for secreting endocrine pancreatic tumors comprise biochemical tests, CT scans, conventional abdominal sonography, angiography and occasionally MR imaging and isotope scans. Due to their small size, insulinomas and gastrinomas, the most common of these tumors, elude these diagnostic procedures. Preoperative sonography and CT scans were negative in over 60%, angiograms in 35% of the patients. The example of a patient with insulinoma demonstrates that in the future endosonography will offer itself as an accurate method with little risk. PMID- 1439403 TI - [The treatment of hemifacial spasm using botulinum toxin]. AB - Hemifacial spasm is a disagreeable disturbance with involuntary unilateral twitching of the facial muscles. Its most common form is supposedly due to an irritation of the facial nerve at its proximal intracranial segment by vascular structures. Various forms of treatment including surgical procedures are employed, very often without satisfactory results but frequently involving the risk for severe complications. For a few years a new method has been using injection of botulinum toxin into the affected muscles, which in the majority of patients relieves the abnormal movements for about half a year; therefore, this very effective and secure procedure is recommended as first-line treatment of hemifacial spasm. PMID- 1439404 TI - [Adrenal cortex carcinoma: diagnosis, therapy and course in 10 cases]. AB - Data from ten cases with carcinoma of the adrenal cortex, diagnosed between 1981 and 1988, have been extensively reevaluated. Six patients suffered from a hormonally active tumor with proven clinical and laboratory signs of hypercortisolism and/or hyperandrogenism. Female patients dominated the cohort (eight of ten). No preference for particular age (35 to 64, mean 52) or lateralisation of the tumor was recognisable. In all cases signs for endocrinopathy and/or tumor disease lead to investigative intervention. Nonspecific symptoms like pain, reduction of weight and fatigue were registered most frequently. In three patients an abdominal tumor was palpable. Investigation of hormone levels and imaging procedures (sonography and CT scan) assured correct diagnosis in all cases. Since prior to operation metastases have been detected in five cases and in eight cases capsular invasion was proven histologically only, one patient was free of tumor after operation but developed hepatic metastases later on. Altogether nine of ten patients developed metastases later on. Seven of the patients died from the perioperative period up to 8.4 +/- 8.15 months. Mean survival of all patients was 20.5 +/- 24.5 months. Histological grading and assessment of anaplasia did not correlate with either survival or tumor stage. None of the patients presented with tumor stage I according to the TNM system by MacFarlane (55). All four patients with advanced disease in stage IV died within the first year after operation. Eight patients were treated with 1 to 6 g of the adrenolytic o,p'DDD (mitotane, Lysodren). In one of these cases, a sonographically documented remission lasting for over eight years was observed. A second patient with anaplastic carcinoma showed a reduction of the size of pulmonary metastases under continuous therapy with o,p'DDD and a cyclic polychemotherapy. After the latter was discontinued, the course was progressive. PMID- 1439405 TI - [Priapism: review of current knowledge and presentation of a diagnostic and therapeutic algorithm]. AB - In medicine, priapism is defined as pathological state: a prolonged, generally painful erection not accompanied by sexual desire not ending with an ejaculation. Rare before 1980, priapism became more frequent after introduction of erection inducing drugs by intracavernosal injections for treatment of impotence. Therefore, the medical practitioner can be faced with this problem, and the authors present with an algorithm the current diagnostic and therapeutic steps based on knowledge of pathology, physiopathology and etiology of this disease. PMID- 1439406 TI - [Clinical-experimental testing of the effects of a new hypnotic on respiratory function in healthy subjects and in patients with chronic-obstructive syndrome]. AB - In a placebo-controlled double-blinded study with ten healthy volunteers and ten patients with obstructive airway disease, the effect of the test compound on respiratory function was measured. Results show that in healthy persons as well patients with obstructive lung disease of slight to moderate degree respiratory functions were not impaired. PMID- 1439407 TI - [A case from practice (246). 1. Chronic pancreatitis due to alcoholism--severe exocrine insufficiency. 2. Erosive bulbitis. 3. Nicotine abuse]. PMID- 1439408 TI - [What is your roentgen diagnosis? Cherry pit ileus with subtotally stenosing colon carcinoma]. PMID- 1439409 TI - [Medical ethics: innovation due to deficiencies?]. AB - A historical follow-up using three examples--euthanasia, choice of therapy for tuberculosis of bones and articulations and economic management of a medical office reveals that comprehensive timeless medical ethics independent from cultural and social influences ('hippocratic oath') do not exist. There are, however persistent as well as increasingly new fields of conflict in daily practise. The latter are partly related to increased medical efficiency. Deficiencies in explicit ethic reflexions and empiric research for coping with such problems led to interdisciplinary medico-ethical work groups and journals over the last years. In this context traditional subjective ethics of care founded on altruism still remain important: The present essay shows, why the new objective and the older subjective approach to moral dimensions of healing professions are mutually founded on each other and should converge in the course of a decision process. PMID- 1439410 TI - [Medicine between technique and ethics]. AB - In modern medicine technical and ethical questions develop continuously into a tension-loaded relationship. The actual controversy between technical and ethical imperative concerns primarily the fundamental dichotomy and dialectics of modern medical technology. In a second part the ethical challenge for physicians and nurses operating in our increasingly perfect hospitals is analysed. An outlook for future conditions for more harmony between medical technology and ethics is finally presented. A new medical spirit is needed to animate medical technology and to expand it to real art of healing. PMID- 1439411 TI - [Ethical problems from the caregivers' viewpoint]. AB - In a first part the different perspective of physician and nurse is outlined. Then the ethical principles of the health professionals are outlined. The variant views--descriptive and normative--are described. In a second part the dilemmas emerging in daily practice of health care workers are demonstrated. Questions regarding the importance of well-being and illness are raised. Does CAN mean also that one SHOULD, i.e. for transplantation of organs? What are the guiding criteria for this advanced medicine. Since ethical decisions always touch at least two human beings they touch us over and over--profoundly. PMID- 1439412 TI - [Ethical problems in geriatrics from the family physician's viewpoint]. AB - The picture of the 'youthful elderly' will develop further in a positive way because elderly people will not only experience a further increase of their average life-expectancy but also of their physical and psychic health and efficiency. Strict adhesion to calendar data means for the elderly that he is easily excluded from social performance and functionality of life. In order to meet the needs and expectations of the elder generation we need more overlapping linking of the different life periods, i.e. more sensitivity for individual arrangements. Increasing burden on the younger generation by increasing multimorbidity and needs for nursing may evoke responsibility for our patients. Therefore we practitioners should readily fulfill our duty to be in charge for the wellbeing of our aging patients. Social sensitivity for dignity in borderline situations depends on the acceptance of illness and needs for nursing as a natural part of our human existence. PMID- 1439413 TI - [Ethics in psychiatry]. AB - In psychiatry there are two major problem areas where ethical questions are of greatest importance. On one hand these are problems arising from commitment to an institution, e.g. forced hospitalisation and forced treatment. Swiss civil law requires in articles 397a to f that such patients may appeal to a judicial court. When this court is a commission comprised of an attorney and of psychiatric and psychotherapeutic specialists, it is of greatest importance that the patient himself be heard by the attorney and not just by a member of the commission and that this attorney also takes into account statements of relatives, as an incompetent patient may say things that are inconsistent with actual facts. As existing or planned hospitalization laws apply mainly to acutely ill patients who are dangerous to themselves or to others, the treatment of chronically ill psychiatric patients cannot be guaranteed. Thus conflicts of conscience arise, since physicians are required to provide medical aid; therefore if such aid is not given or if it is refused, a physician can be sued for inflicting heavy injury. Hence there is an urgent need for judicial measures that guarantee also the treatment of the chronically ill who, like all patients, have a right to be treated. A second problem area is represented by the ethical commissions that decide which scientific investigations may be performed on psychiatric patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439414 TI - [What is your roentgen diagnosis? long-stemmed adenomatous colonic polyp]. PMID- 1439415 TI - [Bronchial asthma]. PMID- 1439416 TI - [Current aspects of analgetics-induced asthma]. AB - Up to 10% of all asthmatics are intolerant to aspirin reacting with bronchospasm after intake of this drug. The triad aspirin-intolerance, glucocorticoid dependent intrinsic asthma and nasal polyps is common in these patients. The reaction to aspirin is not mediated by IgE. Cross-intolerance is observed with all non-steroidal antiinflammatory drugs inhibiting the enzyme cyclooxygenase. If intolerance to aspirin is suspected such drugs have to be strictly avoided. Paracetamol is the alternative in most instances. Only rarely an adaptive desensitization with acetylsalicylic acid is indicated. This method may help to overcome the intolerance. Non-acetylated salicylates occurring also in some foods, preservatives, and food dyes must not generally be avoided in aspirin induced asthma. PMID- 1439417 TI - [Therapeutic aspects in the treatment of juvenile bronchial asthma]. AB - The most important goal of the treatment for bronchial asthma in infants and children is to avoid structural damage to bronchi and lung by the underlying allergic and immunologic inflammatory process. This inflammation is caused by an inherited predisposition to exaggerated mediator-release in the mucosa. Repeated actions of trigger factors maintain this inflammation and provoke exacerbations of asthmatic symptoms. The protective task of the bronchial mucosa can not be fulfilled anymore. General measures of asthma treatment such as prophylaxis against house-dust mite exposure, improved breathing technique and improvement of lung clearance are indispensable measures of an individually adapted, effective symptomatic (bronchodilators) and protective (cromolyn, topical steroids) drug therapy in infants and children with bronchial asthma. A successful therapy should ensure a physiological development of the child. PMID- 1439418 TI - [Bronchial asthma and sports]. AB - Physical exercise can induce an acute attack in most asthmatics. Exercise-induced asthma (EIA) is therefore a common clinical presentation of bronchial asthma. EIA is likely a consequence of bronchial hyperreactivity whereby alterations in bronchial osmolarity, heat-loss by hyperventilation and physical activity per se are discussed as pathogenic triggers. Clinical presentation, pathogenesis and diagnosis of exercise-induced asthma are summarized. Pharmacologic and non pharmacologic possibilities are covered in some depth. In this context the value of sports-therapy in treatment of asthma is redefined. The possibilities and limitations for this form of treatment are explained. PMID- 1439419 TI - [Asthma and ozone]. AB - Ozone and other photochemical oxidants are secondary air pollutants which can damage the respiratory epithelium by their peroxidative properties. As a consequence, inhaled ozone produces diffuse inflammation of the airways, combined with an obstructive ventilatory impairment and long-lasting bronchial hyperresponsiveness. In physiopathological terms, the features observed reflect the characteristics of an asthmatic airway reaction. Thus, ozone seems to be a potential trigger of newly generated asthma in healthy persons and, in addition, may deteriorate the course of the disease in patients with preexisting asthma. The damage induced by ozone depends on the concentration as well as on the amount of inhaled pollutants. According to the duration and the physical activities during ozone-exposure, slight lung function defects have been demonstrated even at concentrations up to 120 micrograms/m3 (60 ppb). Long-term effects of ozone on human health are not yet fully explored; however, the results of a few epidemiological studies give strong evidence of harmful effects by repeated or chronic exposure to photochemical oxidants. So far an increased prevalence of respiratory symptoms and deterioration of lung function could be demonstrated in populations living in areas of high atmospheric pollution. PMID- 1439420 TI - [A case from practice (256). 1. Right-sided gynecomastia possibly drug-induced (Roaccutan). 2. Status following excision and covering of a B-cell non-Hodgkin lymphoma of the skull. 3. Lumbar irritation syndrome of unclear origin]. PMID- 1439421 TI - [What is your diagnosis? Herpetic eczema]. PMID- 1439422 TI - [Epidemiology of falls and hip fractures]. AB - The risk of falling increases with age and with many of the disorders common in late life. Approximately 35 to 40% of community-dwelling people over the age of 65 and up to 50% of institutionalized elderly fall at least once every year. The incidence is highest in women and the very old. Hip fracture, one of the most serious injuries associated with falls, assumes epidemic proportions in old people. In addition to physical injury, falls can have other serious consequences for the older person. Repeated falls are a common reason for the admission of previously independent elderly persons to long-term care institutions. This article examines why older people fall and what factors place persons at risk for falling. The multiple reasons for an inconsistency of the epidemiological data are discussed. PMID- 1439423 TI - [Cardiovascular causes of falls]. AB - Falls with transitory loss of consciousness (syncopes) are mainly due to cardiovascular incidents and show a significant higher risk of injuries than falls without loss of consciousness. The frequency of syncope is increasing with advancing age. Syncope represents an important disease with epidemiologic consequences in the older age group. The broad etiologic spectrum of syncope and the significance of diagnostic methods are discussed. Five case reports are added as illustration. Medical history, clinical examination and ecg-recordings are the most important diagnostic tools in the evaluation of syncope. An in depth investigation of patients with syncope reduces the rate of recurrence and risk for injury, it increases the quality of life and results in lower medical costs. PMID- 1439424 TI - [Epidemiology of osteoporosis]. AB - A representative inquiry (n = 4217) in Zurich revealed that 22% of the female population eats a diet poor in calcium. A connection between calcium-deficient nutrition and other unhealthy lifestyles such as lack of exercise, smoking (> 10 cigarettes/day) and regular alcohol intake (several glasses/day) has been shown by multivariate analysis. Therefore one has to suspect, that every third to fourth woman having several risk factors is at risk at entry in menopause. Primary prevention as a population-oriented strategy is therefore sought by general health-education and prevention of accidents in order to lower risks for fractures. Fractures of the collum femoris alone are on the basis of actual life expectancy in Switzerland responsible for 157,000 hospital days in women and 18,000 in men, corresponding to the annual capacity of an acute-cave hospital with 500 beds. With the aid of a risk-group strategy therefore attempts at secondary prevention are necessary. As a cost-effective screening-test every postmenopausal woman should receive a peripheral quantitative computer tomography. Women with relatively high bone loss-rates and/or low bone density (insufficient stability) could thus be recognized and offered the benefit of an individualized compliance-promoting protective treatment. PMID- 1439425 TI - [Prevention of osteoporosis using hormone substitution]. AB - Since osteoporosis in the postmenopause is predominantly due to estrogen deficiency, adequate hormone replacement therapy is of utmost importance. Estrogens are preventing bone loss and decrease the fracture rate by 95%, but they also improve vasomotor symptoms, psychic complaints and urogenital atrophy and lower the cardiovascular risk very significantly. Since results depend on long term compliance; motivation, appropriate dose, application mode and treatment schedule are therefore decisive. PMID- 1439426 TI - [Rehabilitation following falls of undetermined etiology: results of an intervention study]. AB - In a population of 355 nursing-home patients 35 could be identified with "idiopathic senile gait disturbance" or falls. Out of these, twelve patients were motivated to participate in a trial to improve the gait. Six patients participated in an intensive daily physiotherapy-program for five weeks, six patients served as a control group. Five of the six patients in the intervention group improved the gait to a high degree. The gait analysis documented an abnormal posture due to a long use of walking aids, which was not influenced by the training. The study documents that very old nursing home patients can improve the mobility by intensive gait training if they can be motivated for such therapy. PMID- 1439427 TI - [25 years of pathology at Neuchatel]. AB - The article introduces the Neuchatel Institute of Pathology (INAP) which celebrated its 25th anniversary in 1991. The institute is organised according to the statutes of a private foundation, the State of Neuchatel covering the excess running costs. The task of INAP is fulfilled by its services of clinical pathology which have evolved differently according to each sector. The autopsies reached their peak in 1979, a progressive decline in number is noted since then. The biopsies have increased regularly, especially since 1985. The service of cytopathology has had an irregular development and is actually in full expansion. The article then shows the solutions that INAP has found in the technical and medical fields. The role of medical informatics, introduced in 1983, is pointed out. In conclusion, we discuss the current and future questions of our discipline and their possible solutions in an institution such as ours. PMID- 1439428 TI - [The role of autopsies for the clinician]. PMID- 1439429 TI - [The role of autopsies in clinical medicine and in pathology]. PMID- 1439430 TI - [The Reference Center for Melanomas (CRM)]. PMID- 1439431 TI - [Classification of gastritis according to the Sydney system]. PMID- 1439432 TI - [Carcinosarcoma of the larynx]. PMID- 1439433 TI - [Histiocytoid lobular carcinoma of the breast]. PMID- 1439434 TI - [Splenomegalic lymphoma]. PMID- 1439435 TI - [Medical informatics as a complementary method in medical education]. AB - The practice of the decision making at the bed side especially highlights the place to be devoted to medical informatics both at the pre- and post-graduate levels. Still in a relatively recent past, say the 50s-60s, most of the medical educational efforts were delivered when watching and then imitating the medical behaviour of an older physician. The medical educators were aware that besides the formal lessons related to selected chapters of medical textbooks, there were an obvious need for better training in the ability to make sound clinical judgements. If this ability has been considered only as an artful and intuitive process neither subjected to theoretical analysis nor to be captured in a formal quantitative model, now things have changed to such an extent that it becomes broadly shared that a science of medical decision making can be reasonably founded and this threefold: 1) Upon a formulated logic, 2) The probability theory, and 3) A value theory. The first gives the hand to artificial intelligence (AI) technics, the third to medical information data bases dealing either with patients (like in hospital information systems) or with literature like MEDLINE or electronic "cookbooks". Basically the probabilistic theory is based here upon a priori probabilities related to patients informations and data and opens the way to bayesian decision making. After this little summary it is stressed that educational informatics in medicine would appear either very central or very marginal, if not optional. PMID- 1439436 TI - [Epidemiology of bronchial disorders and the role of atmospheric pollution]. PMID- 1439437 TI - [Respiratory mechanical assistance at home]. PMID- 1439438 TI - [The functional treatment of sprains of the external lateral ligament of the ankle]. PMID- 1439440 TI - [Absinthe and malaria]. PMID- 1439439 TI - [Epidemiology of and preventive medicine in suicide]. PMID- 1439441 TI - [AIDS. Response to the letter by P. Kammerlander et al. on the subject of our article: HIV epidemic: the end of a special law?]. PMID- 1439442 TI - [AIDS-HIV: a little less presumption please]. PMID- 1439444 TI - Cellular and molecular biology of melanoma. AB - Melanoma cells have surface markers that are expressed differently than in normal melanocytes and nevus cells. Monoclonal antibodies may define a phenotypic map of the various melanocytic lesions and can be used in immunohistopathology and immunoscintigraphy. Monoclonal antibodies directed against melanoma-associated glycoproteins and glycolipids are being tested for therapy. Rearrangements or deletions on chromosome 1, 6, and 7 are the most frequently observed cytogenetic abnormalities. Molecular studies have not given a clear picture. A subset of HRAS alleles has been reported to be associated with melanoma. NRAS activation by point mutation has been found in one fourth of the cases. Allele losses at different loci have been reported. Genetic linkage studies have given conflicting results on the presence of a gene for the melanoma-dysplastic nevus syndrome on the short arm of chromosome 1. PMID- 1439443 TI - Cutaneous malignant melanoma: epidemiological considerations. AB - Large geographic and ethnic variations in incidence and mortality rates of cutaneous malignant melanoma (CMM) suggest inverse correlations with the degree of skin pigmentation and latitude. Increases in CMM incidence and mortality rates have occurred in virtually all white populations, more markedly in those that permanently (immigrants) or temporarily (tourists/vacationers) reside in very sunny areas outside their primitive living environment. The interpretation of data from case-control studies is, however, hampered by the difficulties in quantifying retrospectively, but reliably, CMM risk correlates (e.g., host factors, sun exposure, clothing habits, sunburns) in various periods during the life span. There is, thus, a need for large prospective studies on the development of CMM and naevi, ideally in different contexts as concerns host factors, sun exposure, and other life-style habits within and across different populations. PMID- 1439445 TI - Precursor lesions of melanoma: do they exist? AB - The question of whether definite precursors to melanoma exist is answered in the affirmative. Three cutaneous lesions likely to be such precursors are described and discussed as to their clinical and histologic appearance and incidence. Additionally, a type of conjunctival melanosis that has been associated with malignant melanoma of the conjunctiva is discussed and an attempt is made to define it; a proposed classification of this entity is reviewed. Basic approaches to management and analysis of precursor lesions are elaborated. PMID- 1439446 TI - Surgical management of primary melanoma. AB - The outline of the surgical treatment of a primary cutaneous malignant melanoma may be divided into the problems of biopsy, definitive excision and reconstruction of the defect. An excisional, in contrast to an incisional, biopsy provides the full scope of prognostic parameters and should be used whenever possible. General anesthesia is not necessary, and frozen-section examination is inaccurate. An immediate excision biopsy should therefore be performed under local anesthesia as an outpatient procedure. Whenever possible, a margin of 10 mm should be used, as this would mean an adequate and definitive treatment in melanomas up to 1 mm, and possibly 2 mm, in Breslow thickness. In melanomas more than 1-2 mm in thickness a 3-cm free margin instead of a 5-cm free margin is recommended. Many patients, especially those with trunk lesions with a 3-cm free margin may not need a complicated repair, such as a skin graft or a flap. The excision in depth is recommended to be carried perpendicular to the skin and inclusion of underlying fascia is optional, as no study has proved it to be beneficial. The defect after the excision should whenever possible be closed directly. If this is not possible the defect is covered with either a skin graft or a flap and the latter is recommended from both a cosmetic and a functional point of view. If a skin graft has been used, the secondary defect may be reconstructed with a skin expansion technique. PMID- 1439447 TI - Treatment of regional nodes. AB - The appearance of nodal metastases from cutaneous melanoma represents a poor prognosis. Surgery is the only possible treatment for these patients since chemotherapy or immunotherapy have no confirmed specific efficacy in adjuvant or therapeutic schedules. If, for clinically metastatic regional nodes, there is complete agreement on the opportunity of dissection, in the case of clinically uninvolved nodes some controversy exists. For melanomas of the extremities, two different randomized studies have demonstrated no difference in the long-term outcome of patients with stage I melanoma, whether immediate or delayed node dissection is performed. For axial melanomas, although definitive data are not available, there are preliminary statistical results as well as anatomical and technical reasons, suggesting an identical surgical approach to that performed for primaries of other sites. Therefore, apart from specific cases, there is good evidence that node dissection should be planned only for patients with clinically involved regional nodes. PMID- 1439448 TI - Hyperthermic antiblastic perfusion in the treatment of local recurrence or "in transit" metastases of limb melanoma. AB - On the basis of personal experience and a review of the literature, the authors have evaluated the results obtained with hyperthermic antiblastic perfusion (HAP) for the treatment of stage II, III and IIIAB limb melanoma. The evaluation showed that today HAP may be considered a safe and effective treatment, with a major complication rate ranging between 1% and 4%. In terms of tumor response, locoregional control and survival, this treatment has provided better results than other regional chemotherapeutic modalities and undoubtedly better results than those obtained with conventional, even radical, surgery. The multiparametric analysis showed that, of the treatment-related prognostic factors, the minimum tumor temperature influenced the percentage of complete response (CR) to the greatest extent (P < 0.03), with a positive trend also with regard to the dosage of the antiblastic drug employed (P < 0.08). In turn, the complete response rate was a determinant as far as locoregional control (75.3%; P < 0.0009) and disease free (51.4%; P < 0.009) and overall survival (63.2%; P < 0.009) rates were concerned. Of the tumor-related prognostic factors, the number of lesions (P < 0.0014), sex (P < 0.04), and the number of disease recurrences (P < 0.01) appear to influence overall survival. PMID- 1439449 TI - Surgical management of distant melanoma metastases. AB - Disseminated melanoma remains a tumour that is poorly responsive to chemotherapy and radiotherapy. However, this review demonstrates that surgical removal of visceral metastases such as at the, lung or digestive sites, as well as the brain, yields consistent median survivals, often longer than 12 months, and long term survivors. Such surgery is followed by little complication cost and low perioperative mortality. Our experience tends to confirm that complete debulking offers longer survivors as compared to partial. Also, one site of metastases, whatever its anatomical location, when operated on, gives a better chance for survival than when there are multiple sites. PMID- 1439450 TI - Cutaneous melanoma: prognosis and treatment results worldwide. AB - This first metanalysis of melanoma from treatment centers worldwide consisted of 15,798 patients with localized melanoma (stages I and II) and 2,116 stage II melanoma patients with nodal metastases. Comparisons of dominant prognostic variables showed consistent results from center to center, despite the heterogeneity of the patient population. Six of eight centers that performed a multivariate analysis ranked ulceration among the first three most dominant prognostic factors. Men had a higher proportion of ulcerated lesions than did women. There was a positive correlation between ulceration and thickness. Patients with melanoma of the scalp had a worse prognosis than did those with lesions of the face and neck; those with melanomas on the hands had a significantly worse prognosis than did those with lesions on the arms or legs. In this study, women had a statistically significant survival advantage over men. Their melanomas arose in more favorable sites, were thinner, and less ulcerative and had a lower stage of disease at presentation. Stage III melanomas were more common in males, thicker, and more ulcerated and had a nodular growth pattern. Patients with clinically occult nodal metastases detected by pathological examination and those with a single metastatic node fared the best. Five of six centers identified the number of metastatic nodes to be the most significant prognostic factor. Distant metastases (stage IV were analysed at only two centers, which found that the number and site of metastases appeared to be the dominant prognostic features of stage IV melanoma. When all factors were analyzed in a Cox regression analysis, the dominant factors for stage IV melanoma patients were (1) the number of metastatic sites, and (2) the remission duration. There were no histologic criteria of the primary melanomas that predicted the patient's clinical course once distant metastases had developed. PMID- 1439451 TI - [Epidemiology of cerebrovascular accidents]. AB - Recent studies concerning secular trends in stroke incidence and mortality and identification of independent risk factors for stroke are reviewed. Stroke mortality has declined in many industrialized countries in recent decades. In France, it has been declining by more than 30% between 1968 and 1982 in all age groups and in both sexes except for women under 40 years. The decline in stroke mortality seems to be partly real and partly apparent. In the community-based study of Rochester, Minnesota, stroke incidence decreased by 54% between 1945-49 and 1975-79. Recent data from Rochester, however, suggest that the incidence of stroke may no longer be declining. Survival after stroke has also apparently been improving but several sources of potential bias may also have influenced the decrease in reported survival rates. Hypertension is a major risk factor for stroke. Prolonged differences in "usual" diastolic blood pressure of 5 to 10 mmHg are associated with about 40% difference in stroke incidence. Recent analysis suggests that stroke incidence reduction could arise rapidly after hypertension control and that a lower blood pressure should confer a lower risk of vascular disease, even in individuals conventionally considered as "normotensive". There is evidence that cigarette smoking is an important risk factor for stroke with an overall relative risk of 1.5 and that the risk of stroke declines rapidly after the cessation of smoking. A cardiac condition may be a marker for another risk factor or the primary substrate for cerebral embolism. In patients with atrial fibrillation, the risk of stroke is increased through both of these mechanisms. Diabetes mellitus, chronic alcohol consumption (> 3 drinks/day), and high fibrinogen levels are other independent risk factors for stroke. While high levels of cholesterol may be associated with ischemic stroke, an inverse association of the serum cholesterol with the occurrence of intracerebral hemorrhage in men has been reported. In patients with asymptomatic internal carotid stenosis, higher degrees of stenosis convey a higher risk of stroke. However, far from all these strokes are due to thromboembolism from an atheromatous plaque in the ipsilateral internal carotid artery. The relative risk of stroke during the first 5 years following a transient ischemic attack is 7 times that in persons without transient ischemic attack. More than a third of the subsequent strokes occur in a vascular territory different from that of the incident TIA. While the use of oral contraceptives may increase the relative risk of stroke, postmenopausal estrogen treatment may have a protective effect on the risk of vascular diseases. PMID- 1439452 TI - [Hemorrhage of the brain after therapeutic fibrinolysis. 11 cases]. AB - Ten cases of cerebral hemorrhage and one of intraspinal subdural hematoma after thrombolytic therapy are reported. Six patients were treated with streptokinase, four with rt-PA and one with a combination of both drugs. The incidence was 0.5 to 2% and was higher in case of rt-PA therapy (3.7%). In all cases, CT scan showed primary hemorrhage rather than hemorrhagic infarction. Four patients died of stroke. Among the survivors, residual disability was severe in one and mild in five. Only one patient recovered completely. In patients treated with streptokinase, the hemorrhage was probably due to a more than 80% decrease in plasma fibrinogen. In those receiving rt-PA, either excessive dosage (2 cases in our series) or lysis of cerebral microthrombi are thought to be responsible for the hemorrhagic complications. Treatment consists of infection of aprotinin (an anti-fibrinolytic drug), cryoprecipitates with factors V and VIII and protamine sulfate. PMID- 1439453 TI - [Obsessive-compulsive behavior (arithmomania). Atrophy of the caudate nuclei]. AB - We report the case of a 56-year-old woman who died after a 2.5 years progressive course of behavioral disorders associating severe obsessive-compulsive counting with disinhibition. Neuropathological examination showed severe gliosis of the caudate nuclei whereas the lentiform nuclei and frontal cortex were not involved. In contrast with previous reports, this case lacked psychic akinesia which is usually combined with obsessive-compulsive behavior. It is a further illustration of how subcortical lesions can produce a frontal like syndrome. It suggests a fundamental role of the caudate nuclei in the control of behavior. PMID- 1439454 TI - [Postural hypotension with myoclonia in multisystemic atrophy]. AB - Each time he stood up a 60-year old man experienced myoclonic jerks, quickly followed by a syncope due to major postural hypotension. Progressive autonomic failure was associated with pyramidal, extrapyramidal and cerebellar features in a pattern characteristic of Shy-Drager disease. Myoclonic jerks suggested seizures, but no electroencephalographic epileptiform activity was found. This case together with data from the literature suggest, that such involuntary movements may result from cerebral anoxia. PMID- 1439455 TI - [Association of 2 phacomatoses]. PMID- 1439456 TI - [Neurosarcoidosis with meningoencephalitis and tumoral granuloma]. AB - A 24-year old woman had neurosarcoidosis with meningoencephalitis and frontal granuloma. After corticosteroid therapy for two years, CT showed that the granuloma had nearly disappeared and that there was a hydrocephalus. PMID- 1439457 TI - [Sacral perineural cysts. Contribution of magnetic resonance imaging]. AB - In a 41-year old woman complaining of episodic bilateral sciatic pain, MRI showed large sacral cysts developed in the pelvis. The fact that these cysts communicated with the subarachnoidal spaces was not clearly demonstrated by CT. The mechanism underlying the development of this perineural variety of extradural cysts is discussed. PMID- 1439458 TI - [Pilot study of Ginkgolide B, a PAF-acether specific inhibitor in the treatment of acute outbreaks of multiple sclerosis]. AB - Ten patients with relapsing-remitting multiple sclerosis in acute relapse were treated with a five-day course of intravenous ginkgolide B, a specific inhibitor of PAF-acether. Eight patients had improvement of their neurological score, beginning 2 to 6 days after the initiation of therapy. This improvement was sustained in 5 patients and only transient in 3. Two out of these 3 patients with secondary failure and the other 2 who did not respond to ginkgolide therapy, received i.v. methylprednisolone. Three patients experienced mild side effects under ginkgolide therapy but none of the patients had any serious adverse effect. A controlled randomized study is underway, in order to confirm these results and test higher dosages and more prolonged administration. PMID- 1439459 TI - [Confrontation of Salpetriere hospital. May 1990. A vision and language disorder with sudden appearance in a 70 year old patient]. PMID- 1439460 TI - [Epidemiology of micro-organisms responsible for community-acquired pneumonia]. AB - Pneumonias occupy a prominent situation among lower respiratory tract infections where they are remarkable for their potential mortality and for our relative knowledge of the responsible micro-organisms. Analysis and synthesis of each series published must answer several questions, such as: what are the lung diseases considered? which investigations have been performed? which criteria of imputability have been used? in which patients has the study been carried out? in which place, which period and which structure? In spite of methodological lacunae and of the inhomogeneous answers to the questions asked, there is some concordance between the series found in the literature. Thus, more than 90% of community-acquired pneumonias with microbiological identification are caused by Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia psittaci (or pneumoniae), or Influenza A virus. PMID- 1439461 TI - [Photodynamic therapy of bronchogenic cancer]. AB - Photodynamic therapy (PDT) means the activation by light of an exogenous photosensitizer previously retained by tumors. This therapeutic method is under current investigation for lung cancer. A review of the literature presents the preliminary results bearing upon more than 200 epidermoid bronchus carcinomas. A complete response rate of 75% can be anticipated for early tumors. Several survivals beyond five years, due to PDT alone, have already been reported. Two phase III trials are opened, comparing PDT vs YAG laser for obstructing tumors and PDT+Radiotherapy vs Radiotherapy alone for non-operable small tumors. PDT should be developed in selected indications of lung cancer, because it is an original and interesting therapeutic solution. PMID- 1439462 TI - [Isolated pulmonary choriocarcinoma]. AB - The author report a case of isolated choriocarcinoma of the lung revealed in a young woman by a tumoral syndrome of the right base with haematoma. The diagnosis of isolated pulmonary choriocarcinoma was based on the lack of previous gynaecological history and tumour, on the singleness of the lung tumour at CT, and on the high initial beta-CGH level (3,300 ng/ml) in the absence of pregnancy. Surgical resection confirmed the diagnosis and lowered the beta-CGH level to 7 ng/ml. The various aetiopathogenic theories put forward and their relations with the prognosis disparity found in the literature are reviewed. The authors compare the prognosis of isolated pulmonary choriocarcinoma in a non-nulliparous woman to that of placental choriocarcinoma. PMID- 1439463 TI - [An unusual asthma crisis]. PMID- 1439464 TI - [Inflammatory polyp: a rare benign endobronchial tumor]. AB - We report a case of inflammatory polyp in a male patient, which was totally obstructing the left main bronchus but could be removed by simple endoscopic traction. The polyp was responsible for an absence of left lung ventilation which in turn produced by reflex an absence of left lung perfusion completely reversible after removal of the polyp. Inflammatory polyp is a rare benign tumour. Its physiopathology is controverted, but it seems to result from local irritation of the bronchial mucosa. Bronchial endoscopy is the essential examination which in most cases make it possible to diagnose and treat the tumour. PMID- 1439465 TI - [Experience of photodynamic therapy in inoperable bronchogenic cancer in the city of Nancy. Apropos of 3 cases]. PMID- 1439466 TI - [Consensus Conference. Lille, 18 October 1991. Respiratory tract infections. French language Society of Infectious Diseases]. PMID- 1439467 TI - [Why "childhood" asthma"?]. PMID- 1439468 TI - [Models of experimental Haemophilus influenzae and Streptococcus pneumoniae pneumonia in mice]. AB - Streptococcus pneumoniae and Haemophilus influenzae are the bacteria most frequently involved in bronchopulmonary and E.N.T. diseases. Experimental models are useful to analyse in vivo the physiopathological interactions between bacteria and lung tissue and to study the activity of various antibiotics in the focus of infection. Models for pneumococci are devised according to the virulence of the strain, the inoculation technique and the type of animal used. When strains of different virulence and hosts of different lineage are combined, several experimental models with different natural histories are obtained. These experimental models make it possible to study therapeutic measures at different stages, comparing the relative activities of fluoroquinolones, ampicillin and macrolides. For fluoroquinolones, no correlation has been found between in vivo and in vitro data in these models, but the effectiveness of new compounds has been studied. As regard Haemophilus influenzae, lung infection models are rare, either because their septicaemic component is too important or because they do not enable this organism to multiply. Moreover, the models obtained do not lend themselves easily to therapeutic trials and favour those antibiotics that have high serum concentrations. Developing a better model would enable us to improve our knowledge of the pathogenicity of this micro-organism. PMID- 1439469 TI - [Are there metabolic counterindications to the hormonal treatment of menopause?]. PMID- 1439470 TI - [Perineal aponeuroses. An anatomical study leading to the concept of perineal pubic-sacral cord]. AB - On the basis of anatomical dissections, the authors offer a description of the perineal thickness (centred on the study of its aponeuroses) which corresponds better with medical imaging (ultrasonography, MRI) findings. Situated between the pelvic floor (deep layer of the deep perineal aponeurosis) and the perineal skin (covering the superficial layer of the superficial perineal aponeurosis), the perineal thickness is organised around an antero-posterior functional entity: the pubic-sacral perineal cord. This is made up, from behind and going forwards, of: the urethro-clitorido-vulval entity, the peri-vulval insertion of the perineal aponeuroses, the tendinous centre of the perineum and the ano-coccygeal raphe. It forms the keystone of the perineal thickness by closing off the floor of the urogenital fossa, the transit point for prolapses. This organisation of the perineal thickness explains how the vulval orifice, with no truly effective specific muscular structure, opposes the forces of abdominal pressure, thus avoiding the development of prolapse under normal circumstances. The ischio rectal fossa is also studied. PMID- 1439471 TI - [Uretero-vesical injuries during pelvic surgery in women]. AB - Injuries to the ureter and the bladder are common complications in female pelvic surgery. Unfortunately, they remain often unrecognized per operatively. Intravenous pyelography and renal ultrasonography are very efficient for post operative diagnosis. The indications of nephrectomy have became rare because of the efficacity of the procedures of plastic and reconstructive urological surgery. PMID- 1439472 TI - [Evaluation of the method of delivery in breech presentation]. AB - The authors report a retrospective study based upon 543 breech deliveries at term, collected between 1987 and 1990. The cesarean section rate was 18.4 per cent. It was prophylactic in 56 cases. When the possibility of vaginal delivery was accepted, cesarean section was performed in 9 per cent of cases. Fetal mortality and morbidity were higher with vaginal delivery. However, maternal morbidity was greater in the cesarean section group. Study of the literature shows that the increase in cesarean section rate in recent years is not the only factor responsible for improved fetal prognosis. It is therefore important to restrain this increase and find the optimum percentage rate. PMID- 1439473 TI - [Meta-analysis of management seeking to prevent ovular infection]. AB - The prevention of chorioamnionitis after preterm rupture of membranes is still controversial. This is due to the lack of power of most studies. These seem to show that the outcome is mostly determined by the gestational age at membrane rupture and a trend at lower chorioamnionitis when antibiotics are used. PMID- 1439474 TI - [A comparative study of 2 uterotonic drugs during assisted delivery. Ergometrine versus ergometrine combined with oxytocin]. AB - Ergometrine and ergometrine combined with oxytocin were used during assisted delivery for respectively 65 and 60 labours associated with a risk of hemorrhage. Both these substances have a remarkable hemostatic action, though that of ergometrine combined with oxytocin was found to be superior. PMID- 1439475 TI - [Characteristics of pregnancy and delivery in women with heart diseases]. AB - The authors report 78 cases of pregnancy in women with heart disease during a 4 year period (1985-1988). Heart disease involved a rheumatic valve lesion in 90 per cent of cases. Heart disease was properly monitored in these patients (74.5 per cent) but the pregnancy in only 50 per cent of cases. These patients gave birth to 78 newborn infants. Labour was premature in 15.38 per cent of cases. Labour was of short duration: less than 6 hours (73 per cent of cases). There was only delivery by cesarean section. Bleeding at the time of delivery was common (12.4 per cent of cases). There were two maternal deaths during the post-partum period (2.56 per cent). Essential risks to the newborn included low birth weight (17.5 per cent) and prematurity (15.38 per cent). Neonatal mortality was 2.5 per cent. PMID- 1439476 TI - [Disseminated peritoneal leiomyomatosis. Apropos of a case]. AB - The authors report a case of disseminated peritoneal leiomyomatosis (DPL) occurring in a post-menopausal woman not using hormone replacement therapy. Her past history included a subtotal hysterectomy, with preservation of the adnexae, for metromenorrhagia due to a leiomyomatous uterus. This case confirms data in the literature concerning presentation, symptomatology, macroscopic appearance and histology. No electron microscopy study was undertaken, nor were hormonal receptors evaluated. The originality of this case lies in the onset of DPL in a post-menopausal (with laboratory confirmation) woman with very slow progression over several decades confirming the hormone-dependent nature and the good prognosis of this rare condition. PMID- 1439477 TI - [Vesico-uterine fistulas. Apropos of 2 cases]. AB - Vesico-uterine fistulas (VUF) are an increasingly rare entity (5% of all urogenital fistulas). The authors report two cases of VUF following cesarean section. The literature is reviewed briefly, indicating that Youssef syndrome is the commonest presentation. This lesion is certainly benign but is a source of discomfort for sexually active women. Treatment is above all preventive. It is based per-partum on perfect management of all cases of difficult labour. Peroperatively, the technique used during each cesarean section must be carefully defined and followed. Treatment of a confirmed VUF is essentially surgical. PMID- 1439478 TI - The pathogenetic aspects of spondyloarthropathies from the point of view of HLA B27. AB - The association of HLA-B27 and seronegative spondyloarthropathies, especially ankylosing spondylitis has been known for almost two decades. The spontaneous development of spondyloarthropathy like joint disease in HLA-B27 transgenic rats verifies the suspicion that the HLA-B27 antigens are directly responsible for disease development. With the recently revealed crystal structure of HLA-B27 and understanding of the class I molecule in general, a new hypothesis can be formulated based on the assumption that the pathogenesis of these diseases is a subversion of the physiological function. PMID- 1439479 TI - Autoantibodies against small cytoplasmic ribonucleoproteins: the anti-Ro/SS-A and anti-La/SS-B autoimmune response. A review of autoantibody detection, autoantigen composition, autoantibody-disease associations and possible etiologic mechanisms. PMID- 1439480 TI - Damage of cultured chondrocytes by hydrogen peroxide derived from polymorphonuclear leukocytes: a possible mechanism of cartilage degradation. AB - To study the mechanisms of chondrocyte damage, chondrocyte cytotoxicity as shown by chromium-51 release induced by polymorphonuclear leukocytes (PMNLs) was examined. PMNLs significantly enhanced chondrocyte cytotoxicity in the presence of phorbol dibutyrate. This chondrocyte damage was abolished by the addition of catalase, whereas superoxide dismutase and scavengers of hydroxyl radicals and protease inhibitors failed to reverse it. When cartilage matrix components such as hyaluronic acid and various proteoglycans were added to the PMNL-chondrocyte cultures, these components failed to affect the chromium-51 release. These results suggest that the increase in chondrocyte cytotoxicity is due to hydrogen peroxide generated by the PMNLs, and that cartilage matrix components do not prevent it. Hydrogen peroxide from PMNLs may therefore play an important role in cartilage degradation through direct damage of chondrocytes during inflammatory process. PMID- 1439481 TI - Persistence of B19 parvovirus in synovial membranes of patients with rheumatoid arthritis. AB - Recent clinical observations support the hypothesis that persistent parvovirus B19 is a triggering factor of rheumatoid arthritis (RA) in certain genetically predisposed individuals. If this hypothesis is correct, a number of RA patients may exhibit parvovirus B19 DNA in their synovial membranes. We tested the synovial tissue and peripheral blood leukocytes of 20 patients with RA, 24 patients with other arthritides or osteoarthritis (non-RA), and 34 healthy blood donors for the presence of parvovirus B19 DNA using specific DNA amplification by polymerase chain reaction (PCR). Using this technique, parvovirus B19 DNA was demonstrated in the synovial biopsies of 75% of patients with RA but in those of only 16.7% of patients with non-RA. In autologous peripheral blood mononuclear cells the percentage of PCR-positive patients was about 15% in both RA and non-RA groups and did not differ from that in healthy controls. When the PCR data were correlated with the presence of anti-parvovirus B19 IgG antibodies in serum and synovia all patients with parvovirus B19 DNA in peripheral blood alone or in both peripheral blood and synovial membrane were seropositive. In contrast, about 40% of patients with parvovirus B19 DNA restricted to the synovial membrane were seronegative. These data indicate a highly disease-related persistence of parvovirus B19 in the rheumatoid synovium. PMID- 1439482 TI - Phenotypic analysis of functionally associated molecules on peripheral blood and synovial fluid monocytes from arthritis patients. AB - Surface expression of 16 different membrane molecules was analyzed in peripheral blood and synovial fluid monocytes from patients with rheumatoid arthritis and reactive arthritis compared to controls. The most significant findings were modulated expression of function-associated FcRI, CR1, CR3, MHC class II and activation-associated CD31, M5, and M6 molecules in arthritis patients compared to controls. Of these molecules, only upregulated expression of MHC class II has previously been reported in synovial fluid monocytes of patients with rheumatoid arthritis. PMID- 1439484 TI - [The contamination of blood cultures. The usefulness of registries]. PMID- 1439485 TI - [The terminal phase of life]. PMID- 1439483 TI - Interleukin-8 in inflammatory rheumatic diseases: synovial fluid levels, relation to rheumatoid factors, production by mononuclear cells, and effects of gold sodium thiomalate and methotrexate. AB - The content of interleukin-8 (IL-8) in the synovial fluid and its production by blood and synovial fluid mononuclear cells (PBMC and SFMC) was compared in rheumatoid arthritis (RA) and various other inflammatory rheumatic disorders. The study included 125 patients and 20 healthy individuals. The highest concentrations of IL-8 were found in the synovial fluids and culture supernatants of PBMC and SFMC from patients with seropositive RA. Only PBMC from seropositive patients, and not from other rheumatic diseases, exhibited significant spontaneous release of IL-8 that correlated with serum IgM rheumatoid factor titers. Gold sodium thiomalate (GST) and methotrexate (MTX) inhibited the spontaneous and stimulated IL-8 production by PBMC by 55-86% at 50 and 10 micrograms/ml, respectively. Two main conclusions were drawn: (1) rheumatoid factors appeared to be a major cause of enhanced IL-8 production in seropositive RA, and (2) inhibition of IL-8-mediated neutrophil migration and activation could be part of the mechanism of action of GST and MTX. PMID- 1439486 TI - [AIDS. A survey]. PMID- 1439487 TI - [Information for those affected by HIV]. PMID- 1439488 TI - [Biochemistry and nursing]. PMID- 1439489 TI - [The professional identity of the nurse]. PMID- 1439490 TI - [Education and European integration]. PMID- 1439491 TI - [Continuous irrigation-aspiration]. PMID- 1439492 TI - [Working conditions in the hospital]. PMID- 1439493 TI - [Ergonomics in health centers. The improvement of the work setting and of the quality of care]. PMID- 1439494 TI - [Health as viewed by the press. Apropos atypical pneumonia]. PMID- 1439496 TI - [15 years later]. PMID- 1439495 TI - [Continuing education. 72. Medical-surgical. Alarm in the ICU. A clinical case]. PMID- 1439497 TI - [The electrocardiograph]. PMID- 1439498 TI - Place-specific derived cochlear microphonics from human ears. AB - The high-pass noise masking technique was used to obtain derived frequency specific cochlear microphonics (CM) from subtracted waveforms to rarefaction and condensation stimuli recorded with a tympanic membrane electrode. Two characteristics suggest that the response is place-specific CM: the derived response retains the same frequency as the stimulating toneburst and the response follows the stimulus polarity. For click stimulation, derived neural responses make the place-specific CM difficult to observe except in the 2-1 kHz derived band. In contrast, place-specific CM evoked by 0.5 and 1 kHz tonebursts can usually be detected in at least three derived bands. The amplitude of the response is largest in the derived band with center-frequency (CF) just above that of the toneburst. This discovery of a place-specific CM offers the possibility of assessing (outer) hair cell function in the apical part of the human cochlea. PMID- 1439500 TI - Effects of adaptation on electrocochleography and auditory brain-stem responses in the elderly. AB - Changes in the amplitude and latency of the evoked potentials in electrocochleography (ECochG) and auditory brainstem responses (ABR) produced by increased stimulus rates (adaptation) were investigated using an extratympanic ECochG technique with simultaneous recording of the ABR in 12 elderly patients, and compared with those of eight normally hearing young adult subjects. Although the absolute latencies of the action potential (AP) and ABR waves were delayed in the elderly, the shift in latency of these components with increased stimulus rate was similar in both groups of subjects. Amplitudes of the AP and wave III component were reduced with increased stimulus rate to a degree which again was similar in both the elderly and young adults. On this basis we suggest that synaptic connections to nerve fibres from surviving hair cells in the elderly are functioning so that disturbance of this part of the acoustic nerve is not a feature of presbycusis. PMID- 1439499 TI - Behaviour of delayed evoked otoacoustic emission under forward masking paradigm. AB - The behaviour of delayed evoked otoacoustic emission (DEOAE) has been studied in normally hearing adults under a conventional forward-masking paradigm, and subjective measurements were carried out additionally for comparison. The clicks served as signals and the noise bursts were used as masker. In different experimental sets, signal and masker intensity, masker duration, and the interval between masker and maskee were altered. At masker levels corresponding to the subjective post-masking threshold of the clicks, the DEOAE was unaffected, i.e. had no noticeable alteration, compared with click stimulation without masking. Even at higher masker levels the inaudible clicks elicited clearly discernible DEOAEs. The forward-masking detection threshold of DEOAE ('DEOAE post-masking threshold') was reached at masker levels approximately 35 dB above the subjective post-masking threshold. The gap between subjective and DEOAE post-masking threshold vis-a-vis the masker level was also evident at different masker durations and different time intervals between masker and maskee. Central neural and peripheral receptor mechanisms are suggested to be the constituents of the masking phenomenon. The neural mechanism is involved at low masker levels. The receptor mechanism effectively joins the neural one at masker levels exceeding the threshold of psychoacoustic masking. The progressive increase in the number of auditory units from the periphery to the centre in the hearing system, linked with an increase in inhibition, can help to explain these effects. PMID- 1439501 TI - The I' potential of the brain-stem auditory-evoked potential. AB - We have consistently recorded a positive wave which precedes wave I, and is called I', within the human brain-stem auditory-evoked potential. It is postulated that I' represents initial neural activity of the auditory nerve, which presumably has as its origin auditory nerve dendrites. Thus, I' may represent a summed far-field dendritic potential from currents of excitatory postsynaptic potentials. We report latency and amplitude values of I'. PMID- 1439502 TI - The super-bass bone-anchored hearing aid compared to conventional hearing aids. Audiological results and the patients' opinions. AB - Twelve patients with severe mixed hearing loss (PTA ranging from 70 to 108 dB HL) were provided with the percutaneous 'super-bass HC 220' bone-anchored hearing aid (BAHA) to replace their former hearing aid. Five had previously worn an air conduction hearing aid (behind-the-ear type, BTE) which could no longer be used because of recurrent otorrhoea; the others had previously worn a conventional (transcutaneous) bone-conduction hearing aid (CBHA) which had caused serious complaints, such as headaches or skin irritation. Free-field speech audiometry in the subgroup of patients who used to wear a CBHA revealed that the maximum intelligibility score with the BAHA was equal to or better than that obtained with the CBHA (range from 0 to +27%). In three of the five patients who used to wear a BTE, the speech scores were poorer with the BAHA than with the BTE (range from -13 to -40%). For the remaining two patients, the difference in scores was 0 and +10%. In conclusion, speech recognition with the BAHA HC220 in the patients with severe mixed hearing loss was comparable to, or better than, that with a CBHA. Compared to an air-conduction hearing aid, the results may be considerably poorer. The results of the questionnaire were in good agreement with the measurements and support the conclusions. PMID- 1439503 TI - Cardiovascular adjustments to high- and low-intensity exercise do not regulate temporary threshold shifts. AB - Sixteen adults cycled for 10 min at low and high intensities--with and without noise. The noise consisted of a 1/3 octave band-filtered noise with a 2,000 Hz center frequency at 104 dB SPL. Regardless of whether or not noise was present, systolic blood pressure increased 14% and 40% above rest during low- and high intensity exercise, respectively. Heart rate also increased above rest (36% and 90%) during low- and high-intensity exercise, respectively. Temporary threshold shifts (TTS) at 3,000, 4,000 and 6,000 Hz could not be differentiated following low- and high-intensity exercise when noise was not present. We report significant TTS at the three frequencies following 10 min of noise exposure with or without low- or high-intensity exercise. TTS was not influenced by either the 14-40% increase in blood pressure or the 36-90% increase in heart rate induced by exercise. The inability of noise alone to influence either blood pressure or heart rate appears to implicate systems other than the cardiovascular in the regulation of hearing sensitivity. PMID- 1439504 TI - The feasibility of using oto-acoustic emissions to monitor cochlear function during acoustic neuroma surgery. AB - The feasibility of using evoked oto-acoustic emission (EOAE) measurement for intra-operative monitoring of cochlear function was assessed during removal of an acoustic neuroma in a 53-year-old woman with normal hearing on the operated side prior to surgery. The high level of noise in the operating theatre was the only material problem encountered and this was not sufficient to prevent recording of identifiable waveforms. During manipulation of the brainstem, damage to the cochlea was indicated by an increase in EOAE latency and its eventual disappearance. A total hearing loss in the operated ear was revealed after surgery. Monitoring cochlear function with EOAEs is probably best considered at present as an adjunct to auditory brainstem response monitoring of the composite cochlea and eighth nerve, thus providing differential information. PMID- 1439505 TI - Phase coherence of the middle-latency response in the elderly. AB - We compared phase coherence of the auditory-evoked, middle-latency response (MLR) and the 40-Hz steady-state evoked potential (SSEP) in two groups of elderly listeners, matched for degree of audiometric hearing sensitivity loss. In group A, speech understanding was appropriate to the degree of audiometric sensitivity loss. In group B, speech understanding was disproportionately poor in relation to the degree of loss. In both modes of measurement (MLR and SSEP) phase coherence was significantly poorer in group B than in group A. In the case of MLR, maximum phase coherence was observed at the expected 40 Hz in group A, but at 30 Hz in group B. In the case of SSEP, maximum phase coherence was observed at 40 Hz in both groups but was poorer at almost all Fourier components in group B. PMID- 1439506 TI - Cochlear and neural dysfunction in acoustic neuroma: can they be separately revealed by auditory brain-stem wave V latency? AB - Cochlear and retrocochlear lesions may be differentiated by a diagnostic index (D5), which is derived from the patient's auditory brain-stem wave V latency and pure-tone hearing threshold at 2 to 4 kHz. The D5 values obtained from 49 cases of acoustic neuroma (AN) have been shown to share some properties with D5 values of patients with cochlear hearing loss (280 cases), indicating a lesser prolongation of wave V latency in cases with pronounced hearing loss. Assuming this finding is indicative of some degree of cochlear impairment concomitant to the neural dysfunction, AN data were corrected in an attempt to remove the effects of cochlear impairment. The resulting D5 values could reflect the delay in wave V solely due to the neural dysfunction. A significant relationship between these D5 values and tumour size seems to support this hypothesis. PMID- 1439507 TI - Psychometric evaluation of the hearing measurement scale on patients registered in a Swedish hearing centre. AB - The hearing measurement scale (HMS), targeting the experience of being hearing impaired, was translated into Swedish and answered by 122 patients with slight to moderate hearing losses. According to the item analysis the test construction of the HMS functions well with a relevant division of the sections. In all sections there were individuals utilizing all response possibilities and the homogeneity (alpha) of the test was high. One exception was section II (hearing non-verbal sounds), which may be due to lack of awareness, indicating that it might not be possible to pursue this dimension by a questionnaire approach. Normative descriptions were given for two age groups: 40 to 60 and 61 to 74 years, including both sexes. The groups had a similar outcome on the HMS, even though the older subjects, on average, had worse hearing problems, measured by pure-tone audiometry. The section covering speech perception had the strongest correlation with hearing loss, while the section covering emotional response entirely lacked such correlations for the younger group. PMID- 1439508 TI - Indices of hearing in patients with central auditory pathology. II. Choice response time. AB - The response times of three groups of subjects with pathology of the auditory pathway, localized either to the eighth nerve or to the right or left temporal cortex, were compared on three psychoacoustic tasks. These tasks included detection, frequency discrimination and duration discrimination. Measurements were made at two stimulus frequencies, 500 and 2000 Hz, in combination with two durations, 50 and 300 ms. The results were compared to those obtained for normal hospitalized and non-hospitalized control subjects. All subjects, except those with acoustic neuroma, had age-corrected normal hearing. Statistically significant group differences were apparent in discrimination but not detection, indicating the importance of task demands for response time measures, especially in patients with cortical pathology. The outcomes were not related to neuropsychological measures of speed or accuracy, supporting the conclusion that the time for decision-making rather than motor function had been affected. PMID- 1439509 TI - Indices of hearing in patients with central auditory pathology. I. Detection and discrimination. AB - This paper describes the effect of site of lesion on auditory detection, discrimination and speech processing. Three groups of ten patients with confirmed pathology of the eighth nerve and right and left temporal cortex and two normal hearing control groups, differing with respect to hospitalization, participated. In each of the fifty subjects, measurements were made of detection thresholds, and difference limens for frequency and duration for 50 and 300 ms pure tones of 500 Hz and 2000 Hz. Consonant discrimination was assessed using the Four Alternative Auditory Feature Test (Foster & Haggard, 1979), presented in quiet. Subjects with left temporal pathology had the largest frequency and duration difference limens. Those with either left temporal or eighth nerve pathology had significantly lower speech intelligibility scores that were correlated with the duration difference limen for short stimuli and detection thresholds, respectively. These findings challenge traditional views of cortical processing and highlight differences between peripheral and central mediators of speech processing. PMID- 1439510 TI - Magnesium deficiency diagnosed by an intravenous loading test. AB - Magnesium deficiency is common but difficult to diagnose and to assess in clinical practice. The use of a magnesium loading test was therefore evaluated to diagnose magnesium deficiency in 661 hospitalized patients with medical conditions assumed to interfere with magnesium uptake and excretion. Thirty millimoles of magnesium sulphate were administered intravenously during 8 h as a loading test and related to the urinary excretion in the following 24 h. A group of 30 patients without any known predisposition for magnesium deficiency and a group of 27 healthy volunteers served as controls. The mean (with 95% confidence interval) magnesium retention was 4 (-2-10)% in the control group of patients and 3 (-2-8)% in healthy subjects. A significantly higher retention was observed in all the groups of the patients: atrial fibrillation 18 (11-25)%, other arrhythmias 18 (11-24)%, hypertension 27 (20-33)%, coronary artery disease 25 (20 30)%, congestive heart failure 31 (26-37)%, cerebrovascular events 38 (24-51)%, gastrointestinal disorders 22 (14-29)%, diabetes mellitus 16 (9-22)%, and alcoholics 33 (29-36)%. The percentage of patients with a retention greater than mean + 2 SD of the two control groups varied between 22% and 54% among the different patient groups. The mean serum magnesium among the patient groups was similar to the control group of patients, except for the alcoholics, hypertensives and young healthy controls, who had significantly reduced levels. Magnesium retention was significantly correlated to age and renal function, and among the alcoholics negatively correlated to serum magnesium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439511 TI - Serum methylmalonic acid before and after oral L-isoleucine loading in cobalamin deficient patients. AB - Over a 1 1/2-year period, we measured concentrations of methylmalonic acid in serum before and after a standardized loading with oral L-isoleucine (100 mmol) in 13 patients admitted for evaluation of cobalamin deficiency. All patients had serum cobalamin values below 100 pmol l-1, but only 12 of the 13 patients were clinically confirmed cobalamin deficient. The clinically non-cobalamin-deficient patient had folate deficiency and was excluded. The serum methylmalonic acid concentrations before loading with isoleucine were above the upper reference limit (0.37 mumol l-1) in all the patients and L-isoleucine caused an increase in serum methylmalonic acid of more than 1.00 mumol l-1 in 11 of the 12 deficient patients. In the remaining patient the increase was 0.35 mumol l-1. The results show that a significant increase of an initially elevated serum methylmalonic acid concentration after isoleucine loading is a general finding in tissue cobalamin deficiency which strongly supports the diagnosis. PMID- 1439512 TI - Clinical evaluation of the Takeda Medical (A & D) TM 2420 ambulatory blood pressure monitor. Practical experience and comparison with direct and indirect measurements. AB - Takeda Medical (A & D) TM 2420 is an automatic ambulatory blood pressure monitoring system employing the auscultatory technique. The device was used under stable conditions and compared to readings from the Hawksley random-zero sphygmomanometer using a double headset stethoscope and a Y-connection. We tested 85 subjects (aged 13-89 years, systolic blood pressure 85-212 mmHg, diastolic blood pressure 40-116 mmHg) and found a difference amounting to 1.6 +/- 6.7 mmHg (mean +/- SD) for systolic and 2.1 +/- 4.5 mmHg for diastolic readings (Hawksley TM 2420). In 62 subjects a comparison with simultaneous measurement on the opposite arm with the Hawksley manometer showed similar results. When comparing intra-arterial readings from 10 subjects, a difference (intra-arterial-TM 2420) of -1.9 +/- 12.1 mmHg was found for systolic pressures, while the diastolic difference was -10.7 +/- 8.7 mmHg. Twenty-four hour monitoring was performed on 80 subjects; 70 of these yielded usable tracings. The proportion of successful recordings was acceptable, but the device was not suitable for bicycle stress testing. The quality of the accessories provided with the equipment could be improved, but in spite of this the monitoring system was found to be recommendable for clinical use. PMID- 1439513 TI - Lipoprotein metabolism following gastroplasty in obese women. AB - In order to elucidate the long-term alterations in cholesterol transport and esterification as a part of the changes in the carbohydrate and lipoprotein metabolism subsequent to calorific restriction, 15 obese women were investigated before and after treatment with vertical banded gastroplasty. Insulin resistance and production, lipid levels in plasma, lipoproteins and the lecithin: cholesterol acyl transferase (LCAT) rate were assessed. There was a 60% decrease in mean calorific intake six months after surgery. A slight hyperglycaemia was almost normalized concomitant with a reduction of serum insulin and C-peptide after 1 year. The very low density lipoprotein (VLDL) level was unchanged. The high density lipoprotein (HDL) levels tended to rise after 1 year, when there was a significant increase of the HDL-2 subfraction. The lipid levels in the lipoprotein fractions showed a rise in mean HDL-2 cholesterol. Both the molar and fractional rates of LCAT were decreased. These results suggest that long-term calorific restriction reduces insulin resistance and production, and lowers VLDL levels and VLDL and cholesterol synthesis. However, the low density lipoprotein cholesterol levels are unchanged, probably because of a decrease in the previously elevated fractional cholesterol removal. PMID- 1439514 TI - Evidence of decreased fibrinolytic activity in hypertensive premenopausal women. AB - In 29 lean, premenopausal, never-treated hypertensive women (142 +/- 2/93 +/- 1 mmHg, mean +/- SEM) plasminogen activator inhibitor (PAI-1) was elevated (11.0 +/ 1.5 U/ml vs 6.3 +/- 1.0 U/ml, p less than 0.05) compared to healthy, normotensive women (113 +/- 2/71 +/- 2 mmHg). Euglobulin clot lysis time tended to be longer in the hypertensive than in the normotensive women (p = 0.06). PAI-1 was positively correlated to triglycerides (r = 0.60, p less than 0.001), haematocrit (r = 0.45, p less than 0.05), insulin (r = 0.38, p less than 0.05) and body mass index (r = 0.38, p less than 0.05), and inversely correlated to HDL cholesterol (r = -0.43, p less than 0.05) in the hypertensive women. Fibrinogen was not significantly different in the hypertensive and normotensive women, while the hypertensive smokers had higher fibrinogen than the hypertensive non-smokers (3.01 +/- 0.17 g/l vs 2.54 +/- 0.10 g/l, p less than 0.05). All participants were investigated in the same phase of the menstrual cycle. Despite that, oestradiol was significantly lower in the hypertensive than in the normotensive women (0.57 +/- 0.06 vs 0.81 +/- 0.09 nmol l-1, p less than 0.05), while progesterone was similar in the two groups. These results suggest that premenopausal, never treated hypertensive women are characterized by low oestradiol levels as well as decreased fibrinolytic activity. PAI-1 seems to be associated with other risk factors for cardiovascular disease in hypertensive women. PMID- 1439515 TI - Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma. AB - The mechanism by which oral oestrogen-containing contraceptives in women and oestrogen treatment of prostatic carcinoma in men increases the risk of vascular disease is unclear. These agents decrease serum concentrations of vitamin B12, pyridoxal 5-phosphate, and folate, all of which are essential for the metabolism of the atherogenic amino acid homocysteine. We found serum vitamin B12 concentrations to be lower in 17 women using oral contraceptives (219 +/- 84 pmol l-1) than in 13 age-matched female controls (385 +/- 129, p less than 0.001), but similar values were obtained in the two groups both for fasting plasma homocysteine concentrations (9.1 +/- 2.4 vs 9.2 +/- 3.6 mumol l-1) and for the increase in these concentrations after methionine loading (19.2 +/- 7.5 vs 17.8 +/- 5.2 mumol l-1). In five men with prostatic carcinoma, high-dose oestrogen treatment decreased serum vitamin B12 concentrations by a mean of 30% (p less than 0.05) within 4 weeks, during which fasting plasma homocysteine concentrations decreased (13.8 +/- 4.5 vs 10.5 +/- 2.8 mumol l-1) and response to methionine loading increased (12.4 +/- 3.4 vs 17.3 +/- 5.1 mumol l-1), though the latter changes were non-significant. Our findings do not support the hypothesis that hyperhomocysteinemia explains cardiovascular risk in women using oral oestrogen-containing contraceptives, or in oestrogen-treated men with prostatic carcinoma. PMID- 1439516 TI - Reference intervals based on hospitalized 'healthy' patients and medical students in relation to analytical bias for serum potassium. AB - The reliability of reference intervals for measurements of serum (S)-potassium in Danish hospital laboratories was investigated (i) by estimation of reference interval based on two different, healthy subpopulations and (ii) by comparison of reference intervals for S-potassium with analytical bias in each of 52 Danish laboratories. (i) The reference values from 227 hospitalized 'healthy' patients were obtained during the period 1979 to 1987 from the first-drawn serum specimen from the hospitalized patients, who were later discharged from the hospital without a diagnosis. The estimated 0.95 reference interval was 3.34 to 4.52 mmol l-1. The other reference sample group consisted of 314 medical students from whom blood was collected in the period from 1983 to 1987. Here the estimated reference interval was from 3.44 to 4.53 mmol l-1. The concentration values from both reference sample groups were corrected for analytical bias (+0.05 mmol l-1). (ii) The 52 Danish laboratories revealed a considerable variability in reference intervals which, regarding the lower reference limit, ranged from 3.2 to 3.7 mmol l-1 in strong contrast to the analytical bias (ranging from -0.08 to +0.15 mmol l 1) in 50 laboratories (two outliers). There was no relationship between lower reference limit and analytical bias in the individual laboratories. It is concluded that analytical performance allows for more uniform (even common) reference intervals throughout the Danish and perhaps Nordic hospital laboratories. PMID- 1439517 TI - Lack of evidence for altered complement and immunoglobulin levels in patients with sickle cell anaemia. AB - Forty-three patients with homozygous sickle cell disease (haemoglobin SS), 24 heterozygous (AS) subjects and 24 controls (AA) from Sudan were investigated by haemolytic activation for complement function via the classical and the alternative pathways, respectively, and by determination of the plasma levels of C3, C4 and factor B as well as of immunoglobulins IgG, IgA and IgM. The study failed to reveal any direct involvement of the complement system in sickle cell disease and nor was any alteration of the immunoglobulin levels registered as a possible cause of increased susceptibility to infections in patients with homozygous sickle cell anaemia. PMID- 1439518 TI - Reference intervals for trace elements in blood: significance of risk factors. AB - A random sample of 100 men and 100 women was examined for whole-blood concentrations of mercury, lead, cadmium and selenium, and the serum concentrations of selenium, nickel, fluoride, aluminium, zinc and copper. Major predictors were sex, hormonal factors (pregnancy, menopause, use of oral contraceptives), age, tobacco smoking and alcohol drinking. Among notable associations, increased blood-mercury was related to the presence of more than four amalgam fillings in the teeth. Blood-mercury correlated with blood-selenium, but a relation to fish intake could only be demonstrated for the former parameter. In women, blood-lead appeared to increase with age, with the highest levels seen after the menopause. Serum-nickel was slightly lower in patients with nickel-related contact eczema. Only the selenium concentrations showed a slight increase in individuals taking mineral supplements. Serum-zinc concentrations decreased considerably during the day. Thus, due to the substantial influence of physiological and environmental factors, individual results must be interpreted in the light of the known predictors for the trace element concentration. However, population-based reference intervals for trace elements in blood are useful to explore geographic and temporal variations. PMID- 1439519 TI - Primary hyperparathyroidism or hypercalcaemia of malignancy? AB - The introduction of two-site immunometric assays measuring intact parathyroid hormone (PTH) and radioimmunoassays measuring PTH-related peptide (PTH-RP) have simplified the evaluation of patients with hypercalcaemia. We present a 63-year old man with recurrent hypercalcaemia after surgical treatment for primary hyperparathyroidism 3 years previously. PTH measured with a mid-region radioimmunoassay gave normal values, at the same level as during his primary hyperparathyroidism. Intact PTH was, however, clearly suppressed, and he had a highly elevated level of PTH-RP. This suggested that he had humoral hypercalcaemia of malignancy. The patient died after 2 months, and at autopsy an adenocarcinoma of the pancreas with no skeletal metastases was found. PMID- 1439520 TI - Serum methylmalonic acid in uraemia. AB - During a 3 month period we measured serum methylmalonic acid concentrations monthly in 37 patients, all on chronic haemodialysis because of end-stage kidney disease. Concentrations of methylmalonic acid in serum were above the upper reference limit in 36 of the 37 subjects. All patients were in regular cobalamin therapy, with intramuscular injections every third month, and all had normal to very high values of serum cobalamin. We found no normalization of serum methylmalonic acid during the examination period after cobalamin injections, and we could not demonstrate any relationship between concentrations of methylmalonic acid and creatinine, cobalamin and creatinine or methylmalonic acid and cobalamin in serum of these subjects. We conclude that an elevated serum methylmalonic acid concentration is a general finding in uraemic patients, and so the assay cannot be used to establish the diagnosis of tissue cobalamin deficiency in these patients. PMID- 1439521 TI - Amount of secondary dentin as an indicator of age. AB - The amount of secondary dentin in a tooth has been used as one of several parameters in methods for age estimation. Dentin deposition has been measured according to various scoring systems, and the Pearson correlation coefficient with age has been found to be approximately 0.6. In the present study of 1000 teeth, molars excluded, secondary dentin was estimated according to three scoring systems. The teeth were prepared according to the half tooth technique. In addition, the area of the coronal pulp and the widths of the root and pulp chamber were measured in a stereomicroscope at the cemento-enamel junction and at three other defined points along the root. The Pearson correlation coefficient between age and secondary dentin varied in different types of teeth. Of the scoring systems, scores according to Johanson were most strongly correlated with age (r = 0.59 to 0.74). Correlation between age and the coronal pulp area varied from -0.47 to -0.72, and the range between age and ratio between pulp- and tooth width at the cemento-enamel junction was from -0.46 to -0.77. Correlations between age and ratio between sum of pulp widths and the sum of tooth widths for all four such measurements ranged from -0.58 to -0.81. Multiple regression analyses showed that by combining several types of measurements, the correlation with age was increased. A tendency was also observed towards reduced speed of secondary dentin formation in the elderly and in women. PMID- 1439522 TI - Effect of stannous fluoride and tetracycline on periodontal repair after delayed tooth replantation in dogs. AB - Previous studies have indicated that inflammatory resorption and ankylosis, which are frequent sequela after delayed tooth replantation, can be greatly reduced by treating the root surface with 1% solutions of stannous fluoride and tetracycline. However, the SnF2 conditioning leaves a long-standing inflammatory reaction in the periodontal ligament. To examine whether a more dilute SnF2 solution would reduce postoperative inflammation without jeopardizing any beneficial effects, anterior teeth in three young adult beagles were extracted and allowed to air-dry for 45 min. They were then immersed in 0.1% SnF2 for 5 min, rinsed in saline, immersed in 1% doxycycline HCl for 5 min, rinsed, and replanted. Control teeth were air-dried and replanted without further treatment. Block biopsies were harvested after 4 wk of healing and processed for histometric analysis. In experimental teeth, 85% of the root surface area showed normal healing, compared to 33% in control teeth. Conversely, resorption and ankylosis were more frequent in controls than in experimental teeth. A persisting inflammatory reaction either adjacent to or at a distance from the root surface was seen in limited areas in both experimental and control teeth. Compared to preceding studies, the findings indicate that reducing the strength of the SnF2 solution from 1% to 0.1% may result in less persistent inflammation, at the cost, however, of less complete prevention of inflammatory resorption and ankylosis. PMID- 1439523 TI - Evidence for xylitol 5-P production in human dental plaque. AB - The Turku sugar studies indicated that xylitol may possess a caries-therapeutic effect. More recent data show that xylitol exhibits a bacteriostatic activity on a wide range of bacteria based on uptake and expulsion of xylitol. Intracellular xylitol 5-P appears to be a key substance associated with inhibition of bacterial metabolism by xylitol. This has been shown in studies with pure strains of bacteria, mainly Streptococcus mutans. The aim of the present study was to examine if production of xylitol 5-P occurs in freshly collected dental plaque which is exposed to labeled xylitol. Plaque extracts were analyzed by thin-layer chromatography combined with autoradiography and high performance liquid chromatography. Strong indications were obtained that xylitol 5-P is readily produced by dental plaque. No other significant xylitol metabolites were identified. The bacteriostatic properties of xylitol in plaque are a mechanism which may well account for the caries-therapeutic effect of xylitol. PMID- 1439524 TI - Evaluation of a photographic method for diagnosis of gingivitis and caries. AB - The aim of the present study was to determine the value of a photographic method when diagnosing gingivitis and caries. 78 patients participated in the investigation. The validity of the photographic method could not be established, since the reproducibility of the clinical diagnosis was not 100%. Instead, the value of the method was determined by comparing the reproducibility of the clinical and the photographic diagnosis. For gingivitis the intra- and inter examiner reproducibilities were best for the photographic readings. For caries the reproducibility of the clinical diagnosis was highest. The photographic method was not limited by method variation when diagnosing redness of the gingiva and caries. However, limitations due to variation were present when diagnosing gingival swelling. The paper also describes the bias reducing capacity of the photographic method. PMID- 1439525 TI - Changes in amount of gingival crevicular fluid after a single episode of periodontal treatment. AB - A total of 51 periodontal sites from 6 adults with no systemic diseases or medication were selected for the study. All sites showed radiologic bone loss and pockets of 4 mm or more. Crevicular fluid (CF) was collected by inserting filter paper strips into periodontal pockets for 5 s and was measured by Periotron. Samples were collected before and 2, 5, 10, 20, and 40 days after a single episode of periodontal treatment (scaling, root planing and curettage). Plaque Index (P1I), Papilla Bleeding Index (PBI) and pocket depth (PD) were measured before and 40 days after treatment. The amount of bone loss was estimated from orthopantomograms taken immediately before the trial. Two days after treatment an increase in the amount of CF was seen. After this the amount of CF decreased, reaching the pretreatment level on day 5 after treatment and a level clearly below pretreatment level on day 10 after treatment. Forty days after treatment a slight increase in the amount of CF was seen. The difference between pretreatment values and values at days 2, 10, 20, and 40 was highly significant. In pretreatment samples, positive correlations were found between the amount of CF and PD, PBI and bone loss and, in samples collected 40 days after treatment between CF and PD. CF measurements made before treatment were of no value in predicting the changes in clinical parameters after treatment. PMID- 1439526 TI - Relationship of collagenase and cathepsin G activity in gingival crevicular fluid. AB - Human neutrophil cathepsin G has been identified as a potent proteolytic activator of latent human neutrophil collagenase in vitro. In order to examine the role of cathepsin G in the activation mechanism of latent human neutrophil collagenase in vivo, gingival crevicular fluid was collected from periodontal pockets of patients with adult periodontitis and the relationship of cathepsin G to the proportion of endogenously active collagenase and total collagenase activity was determined. The changes in these parameters were monitored before and after periodontal therapy and compared to control values obtained for periodontal sites without clinical signs of inflammation or increased pocket depth. A significant decrease in cathepsin G and collagenase activity in gingival crevicular fluid collected from initially deep periodontal pockets was observed in response to scaling and root planing (P less than 0.025, Wilcoxon signed rank test). Also the proportion of endogenously active collagenase decreased (P less than 0.05). There was a significant correlation of cathepsin G and total collagenase activity. However, no correlation of cathepsin G activity and endogenously active collagenase was observed. The results indicate the existence of several distinct activation pathways for latent human neutrophil collagenase in vivo and suggest that, apart from cathepsin G, other proteolytic activation cascades and/or non-proteolytic activation pathways participate in the activation of latent human neutrophil collagenase in vivo. PMID- 1439527 TI - Immune-activation in recurrent oral ulcers (ROU). AB - Tissue specimens from eight patients with recurrent oral ulcers (ROU) were analyzed for possible signs of active lymphocyte involvement. A total of 13 specimens were analyzed, eight (8) taken at the ulcer site and five (5) from clinically unaffected mucosa at a site opposite the ulcer. Monoclonal antibodies or heterologous antisera were applied using the avidin-biotin-peroxidase complex (ABC) or peroxidase-antiperoxidase complex (PAP) methods to visualize cell activation-associated marker proteins. In specimens from the ulcer area, approximately 43 +/- 18% of all inflammatory cells were positive for the MHC locus II coded Ia antigen. Furthermore, markers for cycling cells, interleukin-2 (CD25, 13 +/- 6%) and transferrin (CD71, 23 +/- 14%) receptors, were frequent in the specimens studied. Staining for CD1 (5 +/- 2%) disclosed dendritic intraepithelial cells in diseased and in clinically unaffected mucosa. Mobilization of such cells is suggested by their presence in submucosa in ROU specimens, but not in clinically unaffected mucosa. The presence of CD1 cells, presumably denoting their identity as potent antigen-presenting Lagerhans' cells, and the rich presence of Ia suggest that local conditions are favorable for induction of T-cell-mediated responses. The simultaneous presence in such infiltrates of activation marker positive T-cells suggests activation de facto. This together with the rarity of activated B-cells, i.e. plasmablasts/cells containing cytoplasmic immunoglobulin, suggests active involvement of the local cells of the T-lymphocyte lineage in the pathogenesis of ROU. PMID- 1439528 TI - Force-distance relation and properties of repelling Sm-Co5 magnets in orthodontic clinical use: an experimental model. AB - In recent years, magnets and magnetic forces have been suggested as an alternative to traditional orthodontic devices such as elastics, springs and wires. The purpose of this study was to analyze the reliability and the output of forces for prefabricated orthodontic repelling Sm-Co5 magnets and the force conditions for the magnets after 5 months of maximal loading. The test-machine consisted of a jig where the tested pair of repelling magnets was mounted close to the clinical situation. With a cylindrical strain gauge transducer, a micrometer screw, a bridge-amplifier, and a Mingograph jet recorder, force distance diagrams were constructed. The force-distance diagrams showed that the force-distance curve was hyperbolic and that the mean force when the magnetic pole faces were almost in contact with each other was 214.9 g, SD 13.42 g. The variation of magnetic force between different Sm-Co5 magnets was 6-9%. The difference in force before and after 5 months of maximal loading of the magnets was not significant. The test results indicate that with proper handling of the forces according to the new force diagrams, the system is reliable for orthodontic use. PMID- 1439529 TI - Antibiotic prescribing practices among Norwegian dentists. AB - There is scarce information on antibiotics prescription habits among dentists in general. The present investigation was undertaken to study some patterns of antibiotics prescription among Norwegian dentists. A total of 459 dentists (approximately 10% of Norwegian dentists) were randomly selected, and to each was mailed a letter describing the survey, accompanied by a questionnaire about age, type of practice, educational background and pattern of prescription of antibiotics. 78% of the dentists responded to these questions. The results indicate that during a typical week, 32% did not prescribe antibiotics, whereas 5% wrote greater than 5 prescriptions. The mean weekly number of prescriptions per dentist was 2.04. Periodontists and oral surgeons prescribed antibiotics significantly more often than did general practitioners and other disciplines. In addition, those with research and/or teaching experience seemed to prescribe significantly more often than those without. More than 1/3 of the sample indicated that they may prescribe antibiotics when treating periodontal diseases. Compared with other disciplines, periodontists prescribed such drugs significantly more often when treating periodontitis, but significantly less often in acute gingivitis, stomatitis and herpes simplex infections. Moreover, 22% of the dentists might prescribe antibiotics when the patient is in pain, 73 and 38% in cases of abscesses with or without generalized malaise, 2.5% in endodontic therapy, 60% to prevent general complications, and 68% for prophylactic use if the patient revealed a history of endocarditis. Norwegian dentists are somewhat restrictive in their prescription of antibiotics, but they mostly prescribe the correct drugs for the different conditions. PMID- 1439530 TI - Epithelial adherence to polytetrafluoroethylene (PTFE) material. AB - The aim of this study was to examine adherence/attachment of gingival cellular elements to polytetrafluoroethylene (PTFE) material with special reference to epithelial cells. Six Gore-Tex membranes used for guided tissue regeneration in patients with severe periodontal disease were studied by transmission electron microscopy. Upon retrieval, after 30 days of healing, the membranes were immediately immersed in formaldehyde-glutaraldehyde, divided in segments (2 x 4 mm) and embedded in Epon. The majority of segments were devoid of any adhering tissue other than erythrocytes and polymorphonuclear cells. Epithelial cell adherence was mediated by a 2-microns-thick acellular layer containing membraneous profiles with diameter 370 nm or less. Adhering epithelial cells exhibited characteristics of cellular degeneration as evidenced by tonofilamentous and cytoplasmic condensation, vacuolization and loss of structural details. An uneven basement lamina with hemidesmosomal contacts was present at the epithelium-connective tissue interface. It is concluded that epithelial cells adhere to PTFE material without formation of attachment complexes. PMID- 1439531 TI - Integrated currents between amalgams and a gold alloy in saline solutions and natural saliva with different chloride content. AB - The effect of different sodium chloride concentrations on the integrated currents (charge transfers) between dental amalgams and a gold alloy was studied in a bimetallic cell containing saliva or saline solutions. The integrated currents were only to a minor degree affected by increasing chloride concentrations for the high copper amalgams both in saliva and saline solutions. The integrated currents in the experiments involving conventional amalgam were several times higher than those for high copper amalgams. In saline solutions a charge transfer maximum was found at 0.2 M chloride. In saliva an increase of the charge transfer was found with increasing chloride content. PMID- 1439532 TI - Five-year study of cervical erosions restored with resin and dentin-bonding agent. AB - The cumulative retention rate of a microfilled resin in non-undercut cervical abrasion/erosion lesions was studied over a 5-yr period. The enamel was etched and the dentin was pretreated with either Gluma (n = 75) or the first marketed version of Scotchbond (n = 30). The cumulative 5-yr retention rate of the Gluma fillings was 90% and that of the Scotchbond fillings 47% (the 95% confidence limits were 83-98% for Gluma fillings and 27-67% for Scotchbond fillings). The retention rate with both bonding agents was significantly higher in the maxillary arch than in the mandibular arch. PMID- 1439533 TI - On minimum requirements in education and training for obtaining a license in gastroenterology. PMID- 1439534 TI - Fructose and related food carbohydrates. Sources, intake, absorption, and clinical implications. AB - It is possible to point out subjects consuming considerable quantities of fructose and sorbitol, and the intake seems to be increasing both from added and natural sources. Studies of the absorption of fructose in animals are inconsistent, and the mechanisms of fructose uptake seem to vary in accordance with the species. In most species fructose absorption takes place by a specific carrier (facilitated transport), but it may be active in the rat. In vitro studies of human intestine are very scarce; there is no evidence of active intestinal fructose transport in the human intestine. By means of hydrogen breath tests, a very low absorption capacity for fructose given as the free monosaccharide has been found in humans. Fructose given as sucrose or in equimolar combinations with glucose is well absorbed, and only fructose in excess of glucose is malabsorbed. On this basis it is hypothesized that two different uptake mechanisms for fructose are present in the human intestine. One of these may be a disaccharidase-related uptake system. Sorbitol ingestion may aggravate malabsorption of fructose given as the monosaccharide; it is not known whether a specific mechanism is involved. In children and adults with functional bowel distress the absorption capacities for fructose may not differ from those of healthy individuals, but malabsorption of fructose and/or sorbitol may be the cause of or aggravate abdominal symptoms. Fructose polymers (fructans) are also subject to increasing nutritional interest. Fructans are not absorbed in the small intestine but are strongly fermented in the large bowel. Fructans may be of potential benefit for large-bowel function and blood glucose regulation. PMID- 1439535 TI - The effect of portal perfusion on intrasplenic hepatocytes. AB - A newly developed rat model of portal diversion, in which the subcutaneously transposed spleen is perfused by splanchnic effluent as a result of portal vein ligation, has been used to monitor the effect of such portal perfusion on intrasplenic hepatocyte implants. Three groups of animals (controls, n = 42; transposed only, n = 70; and portally diverted, n = 58) received 2 million syngeneic liver cells. The number of hepatocytes in each spleen was assessed 5 days to 9 months later by direct counting of splenic sections. The transposed spleen was capable of supporting hepatocyte grafts even over long periods, although the number of cells was reduced in comparison with controls. Diversion of portal flow across the transposed spleen significantly increased hepatocyte numbers in the first 6 weeks (median number of cells (with inner quartile range), 1380 (70-1300) versus 600 (347-4050); n = 75), but no differences were detected thereafter. It appears that the initial lag phase of hepatocyte grafts can be partially abrogated by portal perfusion, but the subsequent 'proliferative' phase is unaffected. These effects correlate well with established theories on the importance of portal flow to the intact liver. PMID- 1439536 TI - The anatomic range of examination by fibreoptic rectosigmoidoscopy (60 centimetres). AB - The purpose of the study was to investigate the anatomic location of the flexible rectosigmoidoscope (60 cm) when introduced as far as technically possible. One hundred and forty-nine consecutive patients referred for double-contrast enema (DCE) were examined with rectosigmoidoscopy before the radiologic examination, and CO2 was used for insufflation. A plain abdominal film was taken to locate the tip of the instrument when 60 cm or as much as possible of the instrument had been introduced. The sigmoid loop was passed and the tip of the scope located in the ascending colon or at the left flexure in 99 (66%) of the patients, and in a further 27 (18%) the upper part of the sigmoid colon was reached. The sigmoid colon had been passed in 71%, 80%, and 44% when 60, 50, and 40 cm of the instrument was introduced, respectively. DCE could be performed at the same session as the rectosigmoidoscopy, as CO2 was quickly absorbed. In the vast majority of patients the sigmoid colon can be inspected with a rectosigmoidoscope. PMID- 1439537 TI - Proliferative activity of bile duct epithelium after bacterial infection in dogs. AB - To clarify the relationship between proliferative activity in bile duct epithelia and bacterial infection in the dog, we induced obstructive cholestasis with a bacterial infection in two lobes of the liver. The bile duct branch draining the left lateral lobes of the liver was cannulated in all mongrel dogs. The dogs were divided into three groups and treated as follows: in group 1 the cannula was clamped after the injection of 10(7) Escherichia coli (aerobic bacteria) and 10(7) Bacteroides fragilis (anaerobic bacteria) cells; in group 2 the cannula was clamped after the injection of 10(7) E. coli cells; and in group 3 the cannula was clamped without the injection of any bacteria. Three months and 9 months later dogs from each group were killed, and their livers were examined. In the group 1 dogs papillary hyperplasia and severe dysplasia were noted in association with chronic cholangitis at 3 months and 9 months, respectively, after operation. In the group 2 dogs periductal fibrosis was severe, but epithelial papillary hyperplasia was less pronounced than in the group 1 dogs at each period. In the group 3 dogs no periductal fibrosis or epithelial papillary hyperplasia was seen at either 3 or 9 months postoperatively. These findings suggest that papillary hyperplasia and/or severe dysplasia of the bile duct epithelium may be caused by aerobic and anaerobic bacterial infection of the biliary tract in combination with bile stasis. PMID- 1439538 TI - 1-year survey of patients with advanced liver cirrhosis. Prognostic value of clinical and laboratory indexes identified by the Cox regression model. AB - The relation between coagulation indexes and survival rate was studied and analyzed in 46 patients with advanced liver cirrhosis (grade B and C Child-Pugh Classification), during a follow-up of 1 year. Twenty-four patients (52%) died of liver failure or fatal haemorrhage within 12 months of follow-up. Prothrombin activity, fibrinogen, fibrin(ogen) degradation products, prekallikrein and factor VII, serum bilirubin, and the degree of liver insufficiency, scored by Child-Pugh classification, proved to be significantly correlated with survival by univariate analysis. A multivariate survival analysis (Cox regression model) disclosed two variables, prekallikrein and factor VII, that predicted survival. The rate ratios of death increased to 2.8 and 7.6 with values of prekallikrein < 26% and factor VII < 39%, respectively. This study shows that some simple laboratory tests exploring the clotting system may identify patients with poor prognosis in severe liver failure. PMID- 1439540 TI - Suppression of anger and gastric emptying in patients with functional dyspepsia. AB - Psychologic distress and gastric motor dysfunction have both been implicated in the pathogenesis of functional (non-ulcer) dyspepsia (FD). This study assesses the association between psychologic factors and gastric emptying in 28 FD patients. Subjects completed an extensive range of psychologic questionnaires and underwent dual-isotope scintigraphic assessment of solid and liquid gastric emptying. Attempts to resist, control, suppress, and hold in anger, to adopt a fighting spirit whilst dealing with chronic stressors, and manifest unhappiness were predictors of prolonged gastric emptying. These findings suggest that psychologic factors may be important in the aetiology of gastric stasis and subsequent upper gastrointestinal symptoms in patients with functional dyspepsia. PMID- 1439539 TI - Effect of Helicobacter pylori on parietal cell sensitivity to pentagastrin in duodenal ulcer subjects. AB - We have investigated the possibility that hypergastrinaemia in chronic Helicobacter pylori infection is a compensatory response to reduced parietal cell sensitivity to gastrin. The acid response to 45-min infusions of pentagastrin at sequential doses (micrograms/kg/h) of 0, 0.031, 0.062, 0.124, and 0.6 was compared before and 1 month after eradication of H. pylori in eight duodenal ulcer patients. The median acid outputs (mmol/h) with the respective infusions were 5.0, 7.5, 26.5, 30.8, and 37.0 when H. pylori-positive and similar at 4.5, 7.1, 22.7, 28, and 31.5 when H. pylori-negative. The median estimated dose of pentagastrin required to produce 50% maximal response (D50) was similar before (0.060 micrograms/kg/h) and after (0.057 micrograms/kg/h) eradication of H. pylori. The median estimated maximal response to pentagastrin (mmol/h) was also similar before (39.2) and after (32.3) treatment. The median basal gastrin concentration was 48 ng/l (range, 22-77) before treatment and fell to 33 ng/l (range, 8-37) after eradication of H. pylori (p = 0.03). These findings show that the parietal cell sensitivity to pentagastrin is unaffected by chronic H. pylori infection in duodenal ulcer subjects and that the hypergastrinaemia cannot be attributed to the bacterium inhibiting parietal cell function. PMID- 1439541 TI - Stereologic investigations of human gastric mucosa. II. Oxyntic mucosa from patients with Zollinger-Ellison syndrome. AB - Biopsy specimens from the oxyntic mucosa were obtained on 210 occasions from 76 patients with the Zollinger-Ellison syndrome (ZES) before and during omeprazole treatment. One-micrometer sections were examined by light microscopy, and in 5% linear hyperplasia of endocrine cells was observed. Morphometry was carried out in 91 of the specimens and showed a significant increase of the mean endocrine cell density in comparison with both young, healthy subjects and patients suffering from active peptic ulcer disease (PUD). No metaplasia, dysplasia, or neoplasia was detected in patients with ZES, and the mean mucosal thickness and parietal cell density remained normal. The parietal cells often displayed endosome-like structures, and occasionally there were lingulate cytoplasmic projections into the gland lumen. Electron microscopic morphometry was carried out in specimens from nine patients with ZES and did not show any significant differences in the parietal cells in comparison with healthy subjects. PMID- 1439542 TI - Location and type of gastric carcinoma in relation to pepsinogen I level in blood. AB - Serum pepsinogen I (PGI) levels were measured in 192 gastric carcinoma (GC) patients and 70 controls. Among GC patients serum PGI levels were not influenced by the following variables: age, sex, smoking, Borrmann's or Lauren's classification, tumor size, cellular differentiation, and layer of invasion. The mean serum PGI levels of tumors restricted to the body, antrum, or involving both areas were 64.8 +/- 37.6 ng/ml, 76.0 +/- 47.0 ng/ml, and 51.1 +/- 25.5 ng/ml, respectively (P < 0.005). Odds ratios of GC patients from the quartile of 262 serum PGI levels in the limits > or = 100 ng/ml, 70-99.9 ng/ml, 45-69.9 ng/ml, and < 45 ng/ml were 1.00, 0.76, 3.44, and 37.1, respectively (P < 0.001). The lower serum PGI levels of Chinese GC patients seem to be related to disease location rather than other characters of the tumor. PMID- 1439543 TI - Computer-aided decision support in hepatology. AB - The aim of this study was to describe and to evaluate the publications of the last 30 years devoted to computer-aided decision support in clinical hepatology. The search used Medlars and references of articles. Computer-aided decision support (CADS) was classified in two categories: statistical systems and knowledge-based systems. Two specific questionnaires were used for methodologic evaluation, one for statistical systems and one for knowledge-based systems. They were filled out independently by two observers. A total of 31 papers were selected among 55 identified between 1960 and 1991. The maximum possible for the two scores was 24. The methodologic quality ranged from 4 to 22 (median, 12) for statistical systems and from 8 to 12 (median, 9) for knowledge-based systems. The poor level of methodology could explain in part the lack of utilization of computer-aided decision support in the daily clinical practice of hepatologists. PMID- 1439544 TI - The role of bile in the regulation of exocrine pancreatic secretion. PMID- 1439545 TI - Absorption of wheat starch in patients resected for left-sided colonic cancer. AB - Bacterial fermentation of carbohydrate in the colon, producing short-chain fatty acids (SCFA)--and especially butyrate--has been shown possibly to impede cell proliferation and regulate cell differentiation of colonocytes. In patients with diverticular disease or benign polyps in the colon a hyperabsorption of potato starch in the small intestine has been found. We have investigated the absorption of wheat starch in 15 patients radically resected for cancer in the descending or sigmoid colon, and the results were compared with those of 15 healthy controls. The starch malabsorption was quantified by the hydrogen breath test. The patients malabsorbed 2-14 g (median, 8 g) of 100 g wheat starch ingested, and the control group malabsorbed 3-11 g (median, 6 g) (P greater than 0.1). Mouth-to-cecum transit time for wheat starch and lactulose and the hydrogen production capacity after the lactulose standards were also similar in patients and controls. The results do not support the theory that hyperabsorption of starch is characteristic of patients with malignant disease in the large intestine. PMID- 1439547 TI - Argyrophil cells, mast cells, and histamine in the fundic mucosa of antrectomized patients. AB - Fasting gastrinemia, fundic argyrophil cell density, mast cell number, basal fundic histamine content and histidine decarboxylase activity were determined in 20 antrectomized patients and 20 control subjects. Fasting gastrinemia and fundic argyrophil cell density were significantly lower in antrectomized patients than in controls, whereas fundic mast cell number, basal histamine content, and histidine decarboxylase activity did not differ significantly between the two groups. In antrectomized patients the basal fundic histamine content appears related to the fundic mast cell number, as a consequence of the reduced effect of gastrin on argyrophil cells. PMID- 1439546 TI - Transforming growth factor alpha and epidermal growth factor in protection and healing of gastric mucosal injury. AB - Transforming growth factor alpha (TGF) and epidermal growth factor (EGF) present in the gastric mucosa are polypeptides with similar biologic activity. This study compares the activity of TGF and EGF in the protection against injury by 100% ethanol and stress and in healing of acute gastric ulcerations. TGF and EGF (12.5 100 micrograms/kg-h) infused subcutaneously 30 min before and during ethanol or stress decreased mucosal lesions dose-dependently. The ID50 for ethanol- and stress-induced lesions after TGF were 40 and 70 micrograms/kg-h and after EGF 60 and 100 micrograms/kg-h. TGF and EGF infused subcutaneously into intact rats inhibited gastric acid secretion but did not affect the gastric blood flow or mucosal generation of prostaglandin E2 (PGE2). Both TGF and EGF also significantly enhanced the healing of stress-induced lesions and the restoration of DNA synthesis. Ethanol and stress reduced blood flow in the oxyntic mucosa by 68% and 51%, respectively, and this effect was partially reversed by EGF and TGF. Pretreatment with indomethacin (5 mg/kg intraperitoneally), which reduced mucosal generation of PGE2 by 85%, decreased in part the protection by TGF and EGF against ethanol-induced damage and virtually abolished the protective action of these peptides against stress-induced injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439548 TI - Colonoscopic screening examination of relatives of patients with colorectal cancer. I. A comparison with an endoscopically screened normal population. AB - First-degree relatives (n = 206) of patients operated on for colorectal cancer (CRC) (n = 181) were offered a colonoscopic screening examination; 169 relatives (82%) attended. The findings were compared with those in a normal population sample with no CRC in first-degree relatives (n = 308), aged 50-59 years, who had been screened by means of flexible sigmoidoscopy. Three carcinomas and 176 polyps were found in 56 of 95 male relatives (57%) and 34 of 74 female relatives (46%). The adenoma prevalence rate was 37 (39%) and 26 (35%) for male and female relatives, respectively. In the 50- to 59-year age group, the adenoma prevalence rates for both sexes collectively and for women separately were significantly higher among relatives than among the population without CRC relatives. Hyperplastic polyps were larger, whereas adenomas were similar in size among relatives compared with the normal population. Colonoscopy may be a suitable method of choice for screening first-degree relatives of patients with CRC. PMID- 1439549 TI - Colonoscopic screening examination of relatives of patients with colorectal cancer. II. Relations between tumour characteristics and the presence of polyps. AB - Colonoscopy was offered to 206 first-degree relatives of 181 patients operated on for colorectal cancer (CRC). Findings of polyps in relatives correlated with Dukes staging, extent of dedifferentiation and localization of tumour in the operated patient, and type of family relationship. Adenomas in relatives and Dukes staging of carcinoma in the patients were inversely related. Relatives of patients with Dukes stage A tumour had more than twice as many adenomas as and a higher prevalence of multiple adenomas than relatives of patients with advanced cancer at the time of operation. If the patient had polyp(s) in addition to tumour, the number of adenomas per relative was almost doubled. Hyperplastic polyps in relatives were associated with poorly differentiated carcinoma in their related patients. These results support the theory that not all CRC are derived from polyps and that adenoma-derived CRC may have a better prognosis than 'de novo' CRC. An adenoma prevalence risk table is also presented. PMID- 1439550 TI - Effect of platelet-derived growth factor-BB on indomethacin-induced gastric lesions in rats. AB - The effect of platelet-derived growth factor-BB (PDGF-BB) was evaluated in rats with indomethacin-induced gastric lesions. Animals were treated with either saline solution or several doses of PDGF-BB given orally. Rats treated with 0.1 nmol/kg PDGF-BB showed a statistically significant reduction of gastric damage. Higher doses did not produce any further reduction of gastric damage, and a return toward control values was observed. The effect on lesions was independent of inhibition of gastric acid secretion, since a dose of 0.1 nmol/kg of this growth factor failed to modify gastric acid secretion stimulated by pylorus ligation. PMID- 1439551 TI - Increased protein tyrosine kinase activity of the colonic mucosa in ulcerative colitis. AB - The protein tyrosine kinase (PTK) activity was measured in the inflamed colonic mucosa of 12 patients with ulcerative colitis and in the normal colonic mucosa of 12 control patients with colon cancer. The specific PTK activity in the particulate fraction obtained from ulcerative colitis mucosa was significantly increased compared with that of normal mucosa (5.10 +/- 0.60 pmol/min/mg versus 2.12 +/- 0.44 pmol/min/mg protein; p less than 0.05). Inflamed ulcerative colitis mucosa also showed a significantly higher total PTK activity in the particulate fraction than normal mucosa (2.60 +/- 0.42 pmol/min/g versus 0.91 +/- 0.16 pmol/min/g tissue; p less than 0.05). Mucosal samples from ulcerative colitis patients were divided into those with mild and those with severe inflammation on histologic examination (n = 6 each). The particulate PTK activity of severely inflamed mucosa was significantly higher than that of mildly inflamed mucosa (p less than 0.05). These results suggest that colonic inflammation in ulcerative colitis is associated with alterations in cellular PTK activity. PMID- 1439552 TI - Initiation of anastomotic recurrence of Crohn's disease after ileocolic resection. Onset proximal to the junction and preceded by increased phospholipase A2 activity. AB - Colono-ileoscopy was performed on 11 patients after ileocolic resection for Crohn's disease, to observe development of recurrent anastomotic inflammation and its relationship to mucosal phospholipase A2 (EC 3.1.1.4) activity. Ileal inflammation appeared soon after surgery in eight cases but in none of nine controls with noninflammatory bowel disease. The ileal inflammation was more severe 1-3 cm above than greater than 5 cm above the ileocolic junction (p less than 0.05), whereas the postanastomotic colonic mucosa remained unchanged. Ileal phospholipase A2 activity in the mucosa was equally raised at the two ileal sites (p less than 0.01 and less than 0.02), irrespective of the presence or absence of inflammation. In colonic postanastomotic mucosa the phospholipase A2 activity was the same as in the controls. Further followup showed preanastomotic ileal inflammation at both investigated levels in all patients with Crohn's disease but still with greater severity close to the mucosal junction (p less than 0.05). The study indicates that recurrent inflammation in Crohn's disease is initiated in the terminal ileum close to the ileocolic junction. Progression of severity is accompanied by greater proximal involvement. The increase in mucosal phospholipase A2 activity, which precedes endoscopically detectable inflammation, implies a role for this enzyme in Crohn's disease. PMID- 1439553 TI - Pancreatic morphology and function in adult patients with cystic fibrosis. AB - To determine the relation between pancreatic morphology and pancreatic exocrine and endocrine function, we have studied 8 adult cystic fibrosis patients and 14 normal control subjects by ultrasonography and pancreatic function testing. In the patients with cystic fibrosis the maximum anteroposterior diameter of the pancreatic head was significantly increased over that in control subjects (p less than 0.01), whereas the maximum diameter of the body was significantly decreased (p = 0.05). Increased echogenicity of the pancreatic body was observed in most patients. In the cystic fibrosis patients postprandial insulin secretion was reduced in the 1st h (p less than 0.005 versus control), whereas pancreatic polypeptide secretion was virtually abolished for at least 3 h (p less than 0.01 versus control). All cystic fibrosis patients had evidence of exocrine pancreatic dysfunction as reflected by a diminished urinary para-aminobenzoic acid excretion. Intraduodenal enzyme and bicarbonate output in response to secretin cholecystokinin was reduced in all of three patients studied. It is concluded that loss of endocrine and exocrine pancreatic function in adult cystic fibrosis patients is accompanied by a small and echo-dense pancreatic body relative to a large pancreatic head. PMID- 1439554 TI - Postprandial gallbladder emptying is related to intestinal motility at the time of meal ingestion. AB - The characteristics of meal-induced gallbladder emptying in healthy individuals are subject to wide variation. We hypothesized that some of the observed variation might relate to ingestion of the meal during different phases of the migrating motor complex (MMC). Recording of gastrointestinal pressure was combined with scintigraphic recording of bile kinetics during infusion of 99mTc HIDA. The material consisted of 12 healthy men. Group 1 (n = 6) had a fat-rich meal in phase I, and group 2 (n = 6) had the meal in a phase II. With the end of the meal ingestion as zero, the following results emerged. The subjects in group 1 had a median (range) lag period before beginning of gallbladder emptying of 13.5 (9.0-22.5) min. In group 2 gallbladder emptying began during the meal ingestion in four subjects, and the median lag period was 0 min (minimum, -9.0; maximum, 13.5 (p = 0.02)). The median percentage change of gallbladder counts during the observation period of 54 min in group 1 was 11.5% (from 19% filling to 25% emptying). The corresponding figures in group 2 were 41% (from 2% to 91% emptying (p less than 0.05)). This difference was due to the difference in duration of lag periods, as the emptying rates measured from the end of the lag periods were equal. In conclusion, the onset of postprandial gallbladder emptying relates to the phase activity of the MMC at the time of ingestion. PMID- 1439555 TI - Antigliadin antibody, D-xylose, and cellobiose/mannitol permeability tests as indicators of mucosal damage in children with coeliac disease. AB - A dual sugar (cellobiose/mannitol) permeability test using an iso-osmolar solution was performed, to compare its ability to predict small-bowel mucosal damage in children affected by coeliac disease with the determination of serum levels of D-xylose and antigliadin antibody. Eighty-three children (67 on gluten containing diet and 16 on gluten-free diet) were investigated. The D-xylose and the serum antigliadin antibody test predicted accurately 70% and 78% of the small bowel biopsy results, respectively, whereas the cellobiose-mannitol permeability test predicted 93%. These data confirm the superiority of the permeability test over the D-xylose test, although the former cannot be advocated as a substitute for jejunal biopsy. Our results suggest a complementary use of the permeability test and the antigliadin antibody measurement as screening tests for coeliac disease before applying more invasive procedures. PMID- 1439556 TI - Long-term results after 'floppy' Nissen/Rossetti fundoplication for gastroesophageal reflux disease. AB - Eighty-two patients (median age, 51 years; range, 27-87 years) with refractory gastroesophageal reflux disease (GERD) underwent floppy Nissen/Rossetti fundoplication during the period 1980 to 1990. The median postoperative hospital stay was 5 days (3-16). Median follow-up was 72 months and included endoscopy and a clinical and a questionnaire assessment. Subjective symptoms of reflux were abolished in 98%, and 96% of the patients were satisfied with the results. Endoscopy showed healing of the esophagitis in 98%. There had been no disruption of the fundoplication. Twenty patients complained of gaseous distention and increased flatulence; only two of them had severe problems. Three patients were unable to belch. In conclusion, the floppy fundoplication has been an effective operation with no deaths, a low incidence of morbidity and adverse side effects, and without a tendency for late failure. PMID- 1439557 TI - Changes in the glutathione redox system during ischemia and reperfusion in rat liver. AB - After 60 min of reperfusion following 60 min of ischemia, the ischemia-induced decrease in liver tissue adenosine triphosphate (ATP) concentration had recovered by 66%, and full recovery of mitochondrial function--that is, the respiratory control index (RCI) and the rate of oxygen consumption in state-III respiration (ST III O2)--was observed. In contrast, liver tissue ATP concentration had recovered by only 13%, and marked low RCI and ST III O2 were observed after 60 min of reperfusion following 180 min of ischemia. Intermediate results were observed in rats after 60 min of reperfusion following 120 min of ischemia. Liver tissue hypoxanthine and xanthine, substrates of xanthine oxidase, increased ischemic time dependently. Liver tissue concentrations of the reduced form of glutathione (GSH) and the oxidized form of glutathione (GSSG) and activities of glutathione peroxidase and glutathione reductase did not change after 60 min of reperfusion following 60 min of ischemia. In contrast, GSH concentration and glutathione peroxidase activity decreased significantly after 60 min of reperfusion following 180 min of ischemia. Since the glutathione redox system is an important contributor to the scavenging of free radicals after reperfusion following a long time of ischemia, the free radical scavenging ability might decrease in spite of enhancement of free radical generation, which might play an important role in the inhibition of the recovery of tissue ATP concentrations and mitochondrial function. PMID- 1439558 TI - Hypoxaemia and myocardial ischaemia during and after endoscopic cholangiopancreatography: call for further studies. AB - Sixteen non-selected patients undergoing endoscopic cholangiopancreatography (ERCP) after diazepam premedication were monitored for oxygen saturation (SpO2) with a pulse oximeter and for myocardial ischaemia with a Holter tape recorder from 2 h before ERCP to 6 h after the procedure. One patient was excluded from data analysis because of oxygen therapy. Oxygen saturation was significantly decreased (p less than 0.05) both during endoscopy and in the postendoscopy recovery period. Heart rate was significantly increased (p less than 0.05) both during and after the procedure. ST depression occurred in no patients before endoscopy, in 10 patients during, and in no patients after endoscopy. Concurrent ischaemia and episodic hypoxaemia were found in 5 patients, isolated ischaemia in 7 patients, and isolated episodic hypoxaemia in 13 patients. Concurrent ischaemia and tachycardia were found in 10 patients, ischaemia without tachycardia in no patients, and isolated tachycardia in 1 patient. There was no significant correlation between diazepam dose and SpO2 during endoscopy. These results suggest tachycardia to be more important than hypoxaemia in the pathogenesis of myocardial ischaemia during upper gastrointestinal endoscopy. Cardioprotective measures other than oxygen therapy should soon be evaluated before the implications of the new standards of care in endoscopy have become generally adopted. PMID- 1439559 TI - Is the irritable gut an inflamed gut? AB - Recent advances in the field of neuroimmunology have provided clear demonstrations of i) the neuromodulation of immune function, and ii) the involvement of the immune system in responses induced by psychologic stress in animals and in man. This has led to speculation about the role of the immune system in psychosocial disease. The irritable bowel syndrome (IBS) is characterized by chronic gastrointestinal dysfunction, which may reflect in altered motility, epithelial function, or sensory perception in the gut. IBS is heterogeneous not only in terms of its clinical presentation but also in terms of its pathogenesis, and factors ranging from psychoneurotic behavior and emotional stress, to dietary fiber deficiency, food intolerance, and enteric infection have been implicated. There is evidence of an increase in the inflammatory cells present in the gut of some IBS patients and in an emerging literature that demonstrates the immunomodulation of the motor system of the gut. These findings invite speculation that the immune system may play a role in the pathogenesis and pathophysiology of at least a subpopulation of IBS patients. PMID- 1439560 TI - Idiopathic constipation: any movement? AB - Severe constipation now attracts considerable research interest. As a consequence, there have been recent advances in most aspects of this disorder. The epidemiology of this condition is now better appreciated, and subgroups of patients with different epidemiologies, symptom complexes, aetiologies, and treatments can now be distinguished. Radioisotopes enable detailed transit studies to be obtained of the entire gastrointestinal tract. Careful psychologic evaluation is an essential part of the evaluation. In young women with severe idiopathic constipation there is a decrease in propulsive mass movements, and specific colonic neurotransmitter abnormalities have been identified. Biofeedback therapy is an effective treatment for many of these patients. The variable results of surgery are now also clearly defined. Patients with chronic idiopathic intestinal pseudoobstruction can be categorized on the basis of their pathologic findings; detailed tissue studies may be required. The recognition that severe constipation encompasses various different conditions is leading to a more precise understanding of pathogenesis and treatment. PMID- 1439561 TI - Inflammatory bowel disease: medical therapy revisited. AB - The chronic or recurrent immunologic and inflammatory response in ulcerative colitis and Crohn's disease may be initiated from the gut lumen. Deviation of gut contents away from the inflamed area, bowel rest, or the use of liquid diets appears to benefit Crohn's disease. The relative effects of complete bowel rest, or an elemental, hydrolysed, or polymeric liquid diet have not yet been established. Measures to alter the lumenal bacterial flora, including antibiotics, require further study. The use of corticosteroid drugs can be improved by the use of poorly absorbed or rapidly metabolized compounds. Amino salicylates are effective in ulcerative colitis but require further study in Crohn's disease. Immunosuppressive drugs are valuable not only for a steroid sparing effect but also for control of chronic inflammation. New treatments designed to reduce inflammation are promising but will need to have high potency and an effect at the earliest stages of inflammation before a large number of different inflammatory mediators are released. PMID- 1439562 TI - Nutritional support in inflammatory bowel disease: current status and future directions. AB - Malnutrition is a frequent occurrence in patients with acute inflammatory bowel disease. Total nutritional support provided either parentally (TPN) or enterally (TEN) has been advocated not only as an adjunct for improving nutrition but also as primary therapy. For patients with acute Crohn's disease, short-term rates of remission after TEN are equivalent to TPN. Coupled with certain advantages when compared with TPN, including simpler administration, fewer side effects, and preservation of the intestinal mucosal barrier, TEN may therefore be the preferred route for nutrient delivery. Controlled trials indicate equivalent or superior efficacy when enteral polymeric diets are compared with elemental diets for inducing remission in acute Crohn's disease. Moreover, when provided as an elemental diet, TEN is as effective as corticosteroids for achieving remission in acute Crohn's disease, but corticosteroids appear to be more effective than polymeric diets. Although the provision of nutritional support rather than bowel rest is the major factor contributing to symptomatic improvement, the optimal nutrient composition and the precise mechanisms whereby nutritional support achieves clinical remission remain to be clarified. In contrast to Crohn's disease, nutritional support is not effective for achieving remission in patients with ulcerative colitis. Thus, enteral nutritional support is an effective therapy for the short-term management of acute Crohn's disease. Whether long-term remission is equivalent to treatment with drugs or surgery requires prospective evaluation. Future avenues of investigation also include defining the optimal nutrient composition and the underlying mechanisms that achieve maximal nutritional repletion, promote mucosal cell renewal, and potentially directly retard production of inflammatory mediators. PMID- 1439563 TI - Screening guidelines for colorectal cancer. AB - A review is given of methods and results of screening for colorectal cancer in average-risk and high-risk groups. Possible methods are digital rectal exploration, endoscopic examination, barium enemas, faecal occult blood tests, tumour markers like carcinoembryonic antigen, Ca-19-9, and others, and gene markers. Final results of large randomized population studies with faecal occult blood tests are expected within the next few years, but it will probably be necessary to add flexible sigmoidoscopy to achieve a major reduction in mortality from colorectal cancer in average-risk persons. Recommendations for screening in high-risk groups are proposed, but strong support for these guidelines are still missing, an exception being first-degree relatives of individuals with familial adenomatous polyposis; the other high-risk groups include members of hereditary non-polyposis colorectal cancer families, relatives of patients with sporadic colorectal cancer, patients with colorectal adenomas, patients with previous colorectal cancer, and patients with inflammatory bowel disease. PMID- 1439564 TI - Laparoscopic gastrointestinal surgery. AB - The growth and scope of laparoscopic gastrointestinal surgery are outstripping the ability of medical journals to print series and reports of experience, and much data remain anectodal and preliminary. Laparoscopic cholecystectomy has become established, although, unfortunately, peroperative cholangiography has not yet become normal practice, despite convincing published evidence that it is likely to reduce the increased number of bile ducts that are damaged by laparoscopic surgeons. Imaging the bile ducts and the overall management of choledocholithiasis need re-evaluation, and the approach will change as more surgeons explore the bile ducts laparoscopically. Laparoscopic hiatal anti-reflux surgery will soon be routine, and a whole range of laparoscopically assisted operations on the oesophagus, colon, and rectum will become commonplace. Operations on the liver remain anecdotal. Throughout this rapid progress, surgeons must not forget the principles of (open) surgical practice, whilst carefully kept registers and regular audit of operations will provide new surgical standards. PMID- 1439565 TI - Trefoil peptide expression in intestinal adaptation and renewal. AB - There are many avenues where molecular biology is important in studying the gut, and here we explore methods for defining expression of a new gene family in the gut. We have defined the pattern of trefoil peptide gene expression in the ulceration-associated cell lineage (UACL) and in the nearby mucosa in Crohn's disease. In the UACL, human spasmolytic polypeptide mRNA and peptide are expressed in the acinar and proximal duct cells, whereas pS2 mRNA and peptide are found in the distal duct cells and in the surface cells. In adjacent mucosa, pS2 mRNA and protein are expressed ectopically by goblet cells. Ultrastructural immunolocalisation showed the pS2 to be co-packaged in the mucous cell granules. pS2 peptide was demonstrated in local neuroendocrine cells and was also co packaged with the neuroendocrine granules. The crypts associated with the UACL also showed marked neuroendocrine cell hyperplasia. We have also cloned the newest trefoil peptide intestinal trefoil factor from human and rat intestinal mucosa and shown its co-expression with mucus by normal intestinal goblet cells. The co-packaging of the same secretory protein in both mucous and neuroendocrine granules, which have different functions, is unusual and indicates an important role for pS2 in the secretory process itself or as a ligand delivered to its receptor via multiple routes. We conclude that the trefoil peptides are widely distributed in the intestine in inflammatory bowel disease and are of considerable potential functional importance. PMID- 1439566 TI - New perspectives on acute pancreatitis. AB - The past decade has witnessed considerable changes in the clinical management of acute pancreatitis. Simultaneously, significant advances have been made in understanding the cellular and biochemical events involved in the initiation of this disease. This review summarizes recent clinical and scientific progress regarding acute pancreatitis and suggests areas for future investigation. PMID- 1439567 TI - Non-steroidal anti-inflammatory drug gastropathy and cytoprotection: pathogenesis and mechanisms re-examined. AB - Gastric and intestinal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs) is a common and expensive adverse effect of this class of drugs. While it is likely that inhibition of prostaglandin synthesis by these agents is an important component of their ulcerogenic properties, the pathogenesis of NSAID gastropathy remains unclear. Likewise, the underlying mechanism for prostaglandin 'cytoprotection' is not fully understood, although it is clear from recent clinical trials that prostaglandin analogues are an effective treatment to prevent NSAID gastropathy. In this paper the contribution of neutrophils to the mucosal damage induced by NSAIDs is discussed, as is the possibility that prostaglandins protect the gastrointestinal mucosa from NSAID-induced ulceration at least in part through inhibitory effects on neutrophil function. PMID- 1439568 TI - Primary biliary cirrhosis: new therapeutic directions. AB - The immunologic mechanisms responsible for the development of primary biliary cirrhosis (PBC) remain poorly defined, although recent investigations have provided new clues as to the role of cellular membrane proteins such as the mitochondrial autoantigens and intercellular adhesion molecules. Additionally, new therapeutic agents have become available that markedly enhance the prospect for medical management of both hepatic and extrahepatic manifestations of PBC. Definitive therapy with ursodeoxycholic acid and/or methotrexate, and symptomatic relief of pruritus with rifampicin or metronidazole may become standard in the years ahead. The results of their use to date in the treatment of PBC are detailed in this review. Successful therapy of hepatic osteodystrophy associated with PBC has yet to be achieved, although early data suggest a role for ursodeoxycholic acid, estrogen, calcium, and vitamin D in the management of this debilitating problem. Orthotopic liver transplantation continues to be successful for the management of advanced disease (greater than 70% 5-year survival) and will remain an essential therapeutic tool until definitive medical therapy for PBC becomes available. PMID- 1439569 TI - Hepatitis C: what progress? AB - The new serologic assay for hepatitis C has made it possible to identify patients infected with this agent and to better characterize their clinical illness and its sequelae. As the clinical entity has become better recognized, our understanding of the infectious process has also progressed. Hepatitis C is a chloroform-sensitive RNA virus, only 30-60 nm in diameter, containing a lipid coat. Both erythrocytes and plasma can transmit infection. The viral genome consists of single-stranded linear RNA of approximately 10 kilobases. The first serologic assay developed was a radioimmunoassay, followed shortly by an enzyme linked immunoassay. Secondary tests for specificity now exist. Blood donor populations may have a significant frequency of false positives on the antibody test, making it important that positive results be confirmed with a secondary assay. The antibody is only detected 2 months after infection, by means of currently available assays, and may not appear in many patients until 3 to 6 months after infection. Hepatitis C infection is commonly chronic. This may lead to an asymptomatic chronic carrier state without demonstrable liver disease, or to chronic progressive or non-progressive hepatitis. PMID- 1439570 TI - Modern approach to alcoholic liver disease. AB - The pathogenesis of alcoholic liver disease is unclear. The recent literature on pathogenic factors, including direct effects of ethanol and its proximate metabolite acetaldehyde, associated nutritional factors, the formation of acetaldehyde-protein adducts, associated immune alterations, and the potential for liver injury due to coexisting hepatitis virus infection, is highlighted. The therapy of patients with advanced alcoholic liver injury, especially alcoholic hepatitis, is also controversial. It seems reasonable that all patients should receive adequate nutrition even if parenteral or enteral supplementation is required. Corticosteroid administration may benefit those patients with alcoholic hepatitis who have coexisting spontaneous hepatic encephalopathy and no gastrointestinal bleeding. For patients with complications from end-stage alcoholic cirrhosis, liver transplantation should be considered, as the patient with alcoholic cirrhosis does as well after liver transplantation as those patients with other forms of end-stage liver disease. PMID- 1439571 TI - Issues in gastrointestinal endoscopy: oesophageal varices: inject, band, medicate, or operate. AB - Injection sclerotherapy is the most widely used definitive treatment of acute variceal bleeding and is increasingly performed at the time of the first emergency endoscopy. Direct endoscopic ligation of varices by banding is a new technique under evaluation for both acute bleeding varices and long-term management. Repeated injection sclerotherapy is one of the major options for long term management after variceal bleeding. More major surgical procedures are usually reserved for the failures of sclerotherapy in the management of acute variceal bleeding, whereas portosystemic shunts, particularly the distal splenorenal shunt, or an extensive devascularization and transection operation are commonly used alternative forms of therapy in long-term management. All patients with variceal bleeding should be assessed for liver transplantation, although only a few will ultimately receive a liver transplant. Medication with propranolol is widely recommended in long-term management, but its use in this context remains controversial. The most controversial area of management is prophylactic treatment before variceal bleeding. Major surgical procedures and injection sclerotherapy are not justified at present because it is difficult to identify those patients with a high likelihood of a first variceal bleed. Although medical therapy with propranolol has proved the most successful therapy to date, a case is made for treating most patients conservatively until their first variceal bleed occurs or until better predictive indices for patients at high risk of a first bleed are identified. PMID- 1439572 TI - Gallbladder stones--dissolve, blast, or extract? Laparoscopic cholecystectomy versus 'the rest'. AB - This article reviews selected aspects of the non-surgical/minimally invasive treatments of gallbladder stones (GBS) and discusses briefly the residual role of these treatments in the era of laparoscopic cholecystectomy. In patients with specific, gallstone-related symptoms who wish to retain their 'functioning' gallbladders, there are at least six different management options. They range from rapid but invasive to slow but safe: i) the rotary lithotrite; ii) percutaneous cholecystolithotomy; iii) percutaneous transhepatic or iv) endoscopic retrograde cannulation of the gallbladder followed by instillation (manual or pump-assisted) of contact solvents; v) extracorporeal shock-wave lithotripsy + adjuvant bile acids and; vi) oral bile acids alone. The recommended investigation sequence is i) ultrasound (to diagnose the presence of GBS), followed by ii) oral cholecystography (to assess cystic duct patency, gallbladder anatomy and GBS size, number, lucency, buoyancy, and contour), and iii) regional computed tomography scanning of the gallbladder (to predict stone composition and dissolvability and to plan routes of access to the gallbladder). The decision making steps are i) choice of some form of active treatment versus no treatment (other than observation); ii) in those with specific symptoms and a patent cystic duct who opt for active treatment, to choose between removing versus retaining the gallbladder; and iii) in those who wish to retain their 'functioning' gallbladder, to offer and select the most appropriate of the alternative options. In conclusion, despite the excellence of laparoscopic cholecystectomy, there remains a place for the non-surgical/minimally invasive approaches in a carefully selected minority of symptomatic GBS patients. Although GBS may recur in approximately 50% of patients, the recurrent stones are often asymptomatic, can be detected 'early' by follow-up ultrasound, and are easily treated. Ultimately, the aim of gallstone research must be to prevent not only recurrent but also primary GBS formation, which would obviate the need for both medical and surgical treatment. PMID- 1439573 TI - Endoscopic ultrasonography. AB - Endoscopic ultrasonography (ES) enables accurate imaging of the layering structures of the gastrointestinal tract. The equipment is still evolving but has already reached a high degree of sophistication. The most relevant clinical indications are the analysis of submucosal tumors, the imaging of intestinal vascular anomalies, and, especially, the staging of gastrointestinal and biliopancreatic malignancy and the monitoring of the therapeutic efficacy of surgery, Nd:Yag laser photodestruction, and radiotherapy. PMID- 1439574 TI - Laser therapy: more smoke than light? AB - Lasers have been used endoscopically in the management of gastrointestinal (GI) diseases for 15 years. Although the initial use was for therapy of GI bleeding, other more portable less expensive modalities have supplanted the laser in this area. Currently, its primary application is for therapy of GI neoplasms. If lasers are to be used with increased frequency, it will require that its unique property--selective absorption--be more of a focus than simply using it as a thermal device. Pigmented vascular lesions such as angioma or watermelon stomach are ideally suited for laser therapy using a wavelength preferentially absorbed by hemoglobin. The future use of lasers for gastrointestinal diseases--both diagnostically and therapeutically--will depend on taking advantage of this unique characteristic of laser light. PMID- 1439575 TI - Nonsteroidal anti-inflammatory drugs--the clinical dilemmas. AB - Physicians using nonsteroidal anti-inflammatory drugs (NSAIDs) are concerned that effective anti-inflammatory doses cause few gastrointestinal side effects. Among the causes of discontinuing therapy, upper gastrointestinal symptoms and the development of 'ulcer' complications are major concerns; endoscopic findings in asymptomatic users are not. Initial symptoms, poorly correlated with endoscopic findings, are relieved by anti-ulcer drugs and ameliorate with time of NSAID use in most patients. Symptoms accompanied by epigastric tenderness, or unrelieved by H2 antagonists, or resulting in cessation of NSAID therapy are more predictive of underlying ulcers. Complications probably arise in several ways, including as hemorrhages due to interference with platelet function, and as complications due to exacerbations of underlying ulcer disease or of ulcers caused by the NSAIDs. Pathogenesis and effective prophylaxis (yet to be established) may therefore vary in different patients, a clinical dilemma. PMID- 1439576 TI - Infection and endoscopy: who infects whom? AB - Infection is one of the major hazards of endoscopic procedures and is the commonest complication of endoscopic retrograde cholangio-pancreatography (ERCP) causing death. Prevention of endoscopy-associated infections is based on adequate cleaning and disinfection regimens. Scrupulous mechanical cleaning is fundamental; even prolonged chemical disinfection will be ineffective if cleaning has not been adequate. Special measures are required to prevent ERCP-related infections. It is important to recognize various special circumstances that increase a patient's susceptibility to infection and to administer antibiotic prophylaxis when appropriate. PMID- 1439577 TI - Asleep on the job: sedation and monitoring during endoscopy. AB - Gastrointestinal endoscopic procedures are invasive and carry a significant morbidity and mortality, even for diagnostic procedures (mortality of 1 in 2000 for upper gastrointestinal endoscopy). The commonest causes of death are cardiopulmonary complications, which may in part be related to sedative techniques. The clinical end-points for sedation need to be reappraised and should aim to induce amnesia rather than hypnosis. Endoscopists need to be familiar with the pharmacokinetic and pharmacodynamic properties of the benzodiazepines used for sedation. This applies particularly to the protracted half-lives of some benzodiazepines and the major drug interaction with significant synergy that occurs if opioids are used in combination with benzodiazepines. Thus appropriate doses of these drugs should be administered. The use of supplemental oxygen and pulse oximetry, combined with continuous intravenous access during the procedure should be standard practice. Endoscopists should be aware of national guidelines for safe endoscopic practice. PMID- 1439578 TI - Antiphospholipid antibodies--new insights into their specificity and clinical importance. PMID- 1439579 TI - Effect of mucosal and systemic immunization with pneumococcal polysaccharide type 3, 4 and 14 in the rat. AB - Four immunization routes were investigated to induce an immune response against three structurally different types of pneumoccoccal polysaccharide (PPS) in the rat. In particular, the contribution of the IgA isotype in these immune responses was studied. Six days after administration of PPS type 3, 4 or 14, the localization of specific antibody-containing cells (ACC) in different lymphoid tissues and the antibody titres in serum were studied. All four routes induced anti-PPS ACC in the spleen. After intraduodenal, intravenous and especially intraperitoneal administration of PPS, many IgA-specific anti-PPS ACC were also found in parathymic and mesenteric lymph nodes and in the lamina propria of intestinal tissue. Several anti-PPS ACC were found in Peyer's patches, located peripheral of the B-cell areas. The intratracheal immunization elicited only a local immune response, in bronchus-associated lymphoid tissues and paratracheal lymph nodes. The localization of these anti-PPS ACC was influenced by the route of immunization. After all four investigated routes, specific antibodies were found in serum against PPS. However, some remarkable differences between PPS-3, 4 and 14 were found in the magnitude of the immune response and the distribution of the isotypes. Both route of immunization and structure of the PPS have a profound influence on the immune responses in rats. PMID- 1439580 TI - T-cell receptor V-gene usage in synovial fluid and synovial tissue from RA patients. AB - The question of whether there is a preferential use of certain V genes in T cells entering an inflamed joint has hitherto been studied mainly using unfractionated cells from synovial fluid and tissue respectively, and no clear answer to the question has yet been provided. Concomitantly, evidence has been provided that the use of V genes may differ considerably between CD4+ and CD8+ T cells, and consequently that detection of biased V-gene expression within an inflammatory lesion may require separate analysis of the two T-cell subsets. In this paper we have therefore studied T-cell receptor V-gene expression in rheumatoid arthritis by means of double stainings of synovial fluid and blood for available anti-TCR monoclonal antibodies and antibodies to CD4 and CD8, respectively. Double stainings were also performed with anti-TCR antibodies and antibodies to activation markers HLA-DR and IL-2R. A certain bias towards the preferential use of certain V genes was seen particularly in the synovial fluid samples within both the CD4+ and CD8+ T-cell populations, but no uniform pattern was evident among the 35 patients investigated. PMID- 1439581 TI - Isoelectrophoretic characterization of protein antigens present in mycobacterial culture filtrates and recognized by monoclonal antibodies directed against the Mycobacterium bovis BCG antigen 85 complex. AB - Nine monoclonal antibodies (MoAbs) were produced against Mycobacterium bovis BCG antigen 85 complex. Using isoelectric focusing combined with Western (immunoblot) blot analysis, antigenically related proteins could be identified in culture filtrates from M. tuberculosis, M. bovis, M. Kansasii, M. avium, M. xenopi, M. gordonae, M. fortuitum, M. phlei and M. smegmatis. Most of the MoAbs were found to be broadly cross-reactive between the various mycobacterial species, albeit some minor differences were observed. These MoAbs reacted generally, in each species, with different components. One MoAb (VID1-14) was found to be specifically directed only against antigen 85B from M. bovis, M. tuberculosis and M. kansasii. PMID- 1439582 TI - Analysis of the genomic and derived protein structure of a novel human serum amyloid A gene, SAA4. AB - We have determined the structure of the novel SAA gene, SAA4. The gene is 6.2 kb in length and comprises three introns and four exons. Introns 2 and 3 are significantly longer than those of the other human SAA genes. We have sequenced the exons and junction fragments and have shown that the sequence is the same as c-SAA[1] and does not correspond to the pseudogene carried on GSAA4[2]. The predicted SAA4 protein sequence has an eight amino acid insertion relative to the other human SAA proteins and is more closely related to rabbit and mouse SAA proteins than to the other human SAA proteins, or to those of animal species which also possess an insertion. We have analysed the predicted SAA4 protein relative to the other human SAA proteins and have identified three important structural regions. We predict that region 1 of SAA4 represents a lipid binding domain. Region 2 forms an extensive, distinctive, hydrophobic beta sheet region in place of a helical region. In region 3, SAA4 is the only SAA protein having an alpha helix which is not amphipathic. We predict that the SAA4 protein retains a modified function of the conserved region, retains the Ca2+ binding site, has an amino terminal surface site and has a potentially distinct secretion pattern. Together, these differences indicate a distinct function from those of the other SAA proteins. PMID- 1439583 TI - The role of BCG/PPD-activated macrophages in resistance against systemic candidiasis in mice. AB - The main conclusions of this study are that BCG/PPD-activated macrophages, in contrast to macrophages from control mice, exhibit an increased PMA-induced production of H2O2, kill about one-third of the phagocytosed Candida albicans, and cause more than 50% inhibition of the intracellular formation of germ tubes by C. albicans. Peritoneal macrophages from mice that were colonized post-natally with C. albicans do not show increased production of H2O2 upon stimulation with PMA and the intracellular outgrowth of germ tubes is inhibited to only a limited degree. These macrophages are capable of killing about 20% of the ingested C. albicans. In vivo, the number of Candida in the kidney, spleen and liver after intravenous injection of Candida albicans is significantly lower in BCG-treated mice than in control mice. Post-natal colonization with C. albicans has only a limited effect on the outgrowth of intravenously injected C. albicans in the spleen and liver but does not influence growth in the kidney. These results indicate that acquired immunity against a systemic Candida infection involves both oxidative and non-oxidative mechanisms of intracellular killing and that these mechanisms may have different effects on the yeast and hyphal forms of C. albicans. PMID- 1439584 TI - The effect of disodium cromoglycate on in vitro proliferation of peripheral blood mononuclear cells from allergic and healthy donors. AB - The effect of disodium cromoglycate on in vitro proliferative responses of peripheral blood mononuclear cells from healthy individuals, allergic patients with moderate serum IgE and patients with atopic dermatitis and high levels of serum IgE was investigated. Peripheral blood mononuclear cells were stimulated with mitogens (phytohaemagglutinin, Concanavalin A), recombinant interleukin-2, calcium ionophore + phorbol 12-myristate 13-acetate, purified protein derivative of tuberculin and allergens. It was possible to induce in vitro specific, allergen-triggered responses only in allergic individuals with moderate serum IgE and not in individuals with atopic dermatitis and high serum IgE. Generally, whenever the stimulatory signal(s) caused a significant proliferative response, disodium cromoglycate inhibited the proliferation. This inhibition was seen for all activation agents and for both healthy and allergic individuals. By contrast, for certain non- or low-responders (both healthy and allergic individuals) disodium cromoglycate seemed to amplify the proliferation to various activation signals. Only non- or low-responder cells derived from atopic dermatitis patients showed a biphasic kinetic response pattern when stimulated with the drug in combination with recombinant interleukin-2, recombinant interleukin-2 + ionophore or specific allergens. PMID- 1439585 TI - Antigen-activated T cells inhibit cartilage proteoglycan synthesis independently of T-cell proliferation. AB - Previously we have shown that blood mononuclear cells (MNC) obtained from patients with rheumatoid arthritis (RA) have the capacity to induce depletion of proteoglycans (PG) in human cartilage explants. This was observed especially after stimulating MNC with mycobacterial antigens, rather than with the mitogen Concanavalin A (Con A). We have now co-cultured cartilage explants in the presence of T-cell clone A2b obtained from the rat model of adjuvant arthritis (AA). We show that inhibition of the cartilage PG synthesis is a consequence of antigen-specific T-cell activation and that it is mediated by a humoral factor. This seems to be a cytokine rather than an enzyme. Moreover, at the level of polyclonally responding T cells, inhibition of PG synthesis due to T-cell activation by mycobacterial antigens was shown to depend on prior mycobacterial immunization. Arthritogenic T-cell clone A2b also showed PG synthesis inhibitory effects when co-cultured with cartilage alone. The inhibitory activity was shown to be unrelated to the degree of T-cell proliferation. We conclude that antigen specific T-cell activation may be one of the initiating events leading to cartilage damage in arthritic processes. The measurement of T-cell-mediated PG synthesis inhibition may be a more sensitive and relevant assay for the detection of pathogenic T cells than T-cell proliferation. PMID- 1439586 TI - OKT3-induced cytokine mRNA expression in human peripheral blood mononuclear cells measured by polymerase chain reaction. AB - The kinetic profile of cytokine gene expression in normal human peripheral mononuclear cells (MNC) activated by an anti-CD3 monoclonal antibody was studied. The presence or absence of 10 different cytokine mRNA were measured in a polymerase chain reaction (PCR) assisted mRNA amplification assay. After 2 h of stimulation the mRNA for interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), tumour necrosis factor-alpha (TNF-alpha) and interferon gamma (IFN-gamma) were detectable and remained present during the whole time period studied (22 h). Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were detected after 4 h, while interleukin-10 (IL-10) mRNA did not appear until after 7 h; they all remained expressed at 22 h. A transient expression of interleukin-4 (IL-4) mRNA was observed between 4 and 7 h of stimulation. No gene expression of granulocyte colony stimulating factor (G CSF) was detected at any time. These results show that anti-CD3 stimulation of MNC leads to a rapid sequential induction of different cytokine mRNA, some with a very transient expression. PMID- 1439587 TI - [Pathomorphology of damaged cerebral microcirculation after global ischemia in the dog. Study of the cortical ectosylvian rostral gyrus]. AB - Pathological-morphological changes in the brain microcirculatory blood vessel in dog after global brain ischemia have been evaluated qualitatively. In series of cut sections thick 200 microns dyed with benzidine, a marked microthrombotization of the brain capillaries without vasostasis as well as cylindrical microthrombi and microthrombi with vasostasis were observed. The described light microscopic angioarchitectonic findings account for the phenomenon of vasomotoric paralysis. PMID- 1439588 TI - [A model of mild spinal cord injury in rats--dynamics of changes in motor function]. AB - Authors proceeded by performing compressive spinal traumas of variable intensity in 21 rats at lower thoracic level over an intact dura. The deficit of hind limbs motor functions was evaluated simultaneously with the two tests as follows: a) in observing the gait of an animal along with graduation in accord with modified Tarlov's classification, b) with the method of inclined plane. The reproducibility of injuries of various intensity appeared to be imperfect. Five animals with severe injury died up to 4 weeks (Fig. 4, 5). The remainder of them showed substantial approval (mild injury--Fig. 6-13). The dynamics of motor disorder showed changes up to 6 weeks, after then the state persisted unchanged up to 2 months. Within this survival interval, rats were killed either in the state of mild paresis or even under regained normal condition. It outflowed from our study that a long term monitoring of postinjury spinal cord function is important in order not to ascribe possible approval of the functions to the therapy applied. Further on course of disorder can be predicted in accordance with duration of initial paraplegia. The post-surgery paraplegia had lasted for only several hours in the animals whose injuries resulted in a normal condition. PMID- 1439589 TI - [Non-contact experimental burns in rats]. AB - Both healthy female rats of the Wistar strain (VELAZ breed) and those irradiated with a single whole-body dose of 5 Gy gamma radiation (60Co) were exposed on the back to non-contact infrared radiation (IR lamp with an output of 250 W: skin surface temperature at a distance of 3 cm from the crown of the lamp = magnitude of 110 +/- 2 degrees C) for time periods of 40 s, 20 s, 10 s (healthy) and 20 s (irradiated animals). The surface range of thermic damage to the skin was determined using planimetry and measuring the length and the width of the burn with the respect to an immediate contraction. The mean values of an immediate retraction of the burnt skin and the interval of reliability of their estimate (p < 0.05) were significantly lower in 10 s exposure and in whole-body irradiation rats after 20 s (magnitude of 5.6 +/- 2.5 % ... 10 s; magnitude of 12.56 +/- 3.86 % ... in irradiated animals) than the retraction of non-irradiated rats (magnitude of 15.98 +/- 4.86 % ... in 20 s; magnitude of 31.88 +/- 7.34 % ... in 40 s). For a period of 90 min after burning, no substantial changes were found in rectal temperature (33.4 degrees C to 35.4 degrees C). Before a thermic trauma the drop in the temperature from the skin surface reached cca 2 degrees C subcutaneously, after burning in the centre of the burn about 17 degrees C and 9 degrees C in other exposures using the IR lamp. The mean time of burn healing in non-irradiated animals was the shortest in 10 s exposure (magnitude of 17 +/- 2 days), the damage in the centre reaching II b degree while after 40 s exposure the burn reached IV degree and also the longest healing time (magnitude of 60 +/- 4 days). After 20 s exposure, the mean healing times in irradiated rats were longer (magnitude of 39 +/- 3) days and so the skin damage (III to IV degree) as compared with non-irradiated animals where the mean healing time amounted to (34 +/- 4) days, the burns being of III degree. PMID- 1439590 TI - [Induced cell fusion in a heteroploid cell line]. AB - Non-uniformity in properties of the cells within the stabilized heterocaryonic line is certified by the decrease in capacity of the cells to fuse together after repeated influence of polyethylene glycol. Multiple and large polycaryonic formations resulting from primary administration of fusogen are relatively rapid in extinction. The cells having been survived after repeated administration of polyethylene glycol appear to fuse predominantly into less extended polycaryocytes with smaller multiplicity. This fact may be a consequence of the selection of a portion of non-uniform cell population being more susceptible to this fusogen. Those concerned are probably the cells rather different in surface qualities and/or adjacent parts of cytoskeleton. PMID- 1439591 TI - [The therapeutic effect of diazepam in dichlorvos poisoning]. AB - In order to study the influence of diazepam on both cholinergistic and non cholinergistic (stressogenic) effects of phosphororganic insecticide dichlorovos, both the activity of cholinesterase in selected organs and blood as well as biochemical markers of stress (plasma corticosterone, tyrosine aminotransferase activity in the liver) have been applied. Comparing the course of diazepam treated and untreated dichlorovos intoxication, cholinesterases showed greater increase in inhibition in the first case. There was smaller decrease in activity of acetylcholinesterase in CNS and diaphragm compared with untreated intoxication. Although the changes of plasma corticosterone level were entirely corresponding to those of untreated intoxication, there was still greater increase in activity of tyrosine aminotransferase when compared with untreated intoxication. A marked increase in activity of tyrosine aminotransferase is more convenient for an intoxicated organism, because tyrosine aminotransferase stimulates gluconeogenesis. Even in absence of a complete elimination of cholinergistic and stressogenic effects of dichlorovos, diazepam, as a drug, influenced markedly their course. Thus its significance of component of a complexive atropine-oxime therapy of the intoxication with organophosphates appears to be undiscussible and wider than stressed usually. PMID- 1439592 TI - [Literature findings and suggestions for modification of the fluorometric method for determination of n-acetyl-beta-d-glucosaminidase in urine]. AB - Literature data are summarized on the determination of N-acetyl-beta-D glucosaminidase (NAG) in human urea. Based on these data, the modified determination of NAG activity in urea has been worked out. The latter consists in selection of suitable conditions for providing enzyme reaction and conditioning the area sample used to determine the NAG activity. PMID- 1439593 TI - [Evaluation of the kinetics of the left ventricular wall using the Cardio 200 computer]. AB - The WALLMO program was used in comparing normal kinetic values of left ventricle wall with those obtained from control patients and literature sources. Authors concluded that, when based on the original data for RAO projection, the evaluation of regional LV wall contractility gives erroneous results in estimating whether a given section is normo- hypo- or hyperkinetic. Therefore, the set of normal kinetic values of LV motion has been formed for individual numbers of radials. This set may be used also at other working sites. PMID- 1439594 TI - [The carcinogenicity of gasoline (review of the literature)]. AB - In accord with new findings, the gasoline is no more believed to be free of cancerogenic risk. Renal tumours in male rats and those of liver in murine females had been described also after inhalatory exposure to unleaded gasoline. A reliable epidemiological study in occupationally gasoline exposed humans is still not available (higher rate of tumours in workers of chemical petrol processing industry due to the influence of gasoline appears to be an indirect proof, because apart from gasoline also other substances are involved simultaneously). With regard to a mechanism of action, those first published have been the negative results of testing for chromosomal abnormalities and bacterial genetic mutations. However, the mutagenicity was proved further on molecular level with the use of appropriate tests (e. g. induction of DNA repair synthesis). Certain authors ascribe more importance to the promotional rather than initiational effect of gasoline. However, the former is not accentuated by the IARC. Further studies should be predominantly based on molecular genetic approaches and epidemiological studies. PMID- 1439595 TI - [Comparison of the quality of diagnostic approaches using the characteristic (ROC) curve test]. AB - The method is described to compare the quality of two diagnostic approaches as based on comparing surfaces under the ROC test curve. Apart from small deviations, this method may be applied on independent samples and paired observations carried on identical individuals. Experimental data are issued from comparing two methods of prediction of the survival in dogs on the radiobiologic experiment. PMID- 1439596 TI - Nocturnal enuresis. A new strategy for treatment against a physiological background. PMID- 1439597 TI - Clinical background of patients treated with clean intermittent catheterization in Norway. AB - This study reports on the use of clean intermittent catheterization (CIC) in Norway in 1988/89. A total of 407 adult out-patients was studied. CIC was used in all age-groups and equally in both sex. The patients were divided into five diagnostic groups. There were twice as many patients suffering from neurogenic diseases as non-neurogenic ones. A neurourological index was constructed based on neurological examination and urodynamic data giving a good differentiation and expression of the bladder affection. It appeared that CIC could be performed even by highly disabled persons. A statistically significant correlation was found between the neuro-urological results in patients with decompensated bladder and their over all disability. PMID- 1439598 TI - Autotransposition of vas in a 2-stage procedure. An experimental study in the rat. AB - The patency rate of vasovasostomy in autotransposed vas has been studied using a technique set up in a rat model. In a two-stage procedure, 1 cm of the vas deferens was transposed to the opposite side. The anastomoses were performed with a simplified microsurgical suturing technique. On final examination, 9 of 15 rats operated upon showed good sperm passage over the transposed vas segment. Sperm granulomas were recorded in four of fifteen cases. Sperm antibodies were demonstrated in eight of fifteen cases. PMID- 1439600 TI - The muscularis mucosae of the human urinary bladder. Implications for tumor staging on biopsies. AB - The human urinary bladder wall is traditionally described as being without a muscularis mucosae. A consecutive one year material of 772 bladder biopsies from 171 patients were examined for the proposed presence of lamina muscularis mucosae (MM). MM was observed in 15% of the biopsies and in 35% of the patients and graded into three patterns according to its continuity. Biopsies with transitional cell carcinomas were reviewed in order to find out whether MM positive biopsies had been staged correctly. The data are discussed in relation to earlier studies on the subject. PMID- 1439599 TI - Radical retropubic prostatectomy: our experience with the first 54 patients. AB - Complications were analysed in a contemporary series of the first 54 retropubic radical prostatectomies performed for carcinoma of the prostate at our Institution. The postoperative morbidity was notable; three life threatening and ten minor complications occurred within the first 30 postoperative days. Thus, more than 1 year after the operations 7 patients had severe stress incontinence and 17 noticed minor degree of incontinence. Twenty-six per cent of the patients who claimed to be potent before surgery maintained potency. The operative time averaged 195 min and the demand for transfusions averaged 2.98 units per patient. Our experience in this early series of radical prostatectomy is that the operation cannot be done without notable postoperative morbidity. PMID- 1439601 TI - Cost effectiveness of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy for medium-sized kidney stones. A randomised clinical trial. AB - To evaluate percutaneous nephrolithotomy (PNL) and extracorporeal shock wave lithotripsy (ESWL) for their clinical effects, their cost effectiveness, their complication rates, and the patients' experiences, 55 consecutive patients were randomised to have one or other operation between October 1986 and October 1988. Six patients were excluded, 21 were treated with PNL and 28 with ESWL as primary treatment. Mean hospital stay and length of treatment were longer for PNL than for ESWL. Since 1 July 1987 all patients having ESWL have been treated without anaesthesia (n = 15), whereas epidural anaesthesia was used for all PNL. Slightly more of the ESWL patients experienced some pain during treatment. Minor complications or pain were more common after ESWL during the first 10 days after discharge from hospital. If patients with stone fragments of 4 mm or less were regarded as having a successful outcome, the success rates after one year were 94% for PNL and 77% for ESWL. The overall total cost was lower for ESWL than for PNL, the cost per successfully treated patient being 2172 pounds for PNL and 1810 pounds for ESWL. Medium sized kidney stones (6-30 mm, or 2-3 stones of 20 mm or less) can be efficiently and cheaply treated by both PNL and ESWL, though the cost of ESWL is lower. Even if effects other than cost (such as complications and patients' experience) are borne in mind, ESWL was superior to PNL for this group of patients. PMID- 1439602 TI - Technique of renal biopsy by ultrasound guided percutaneous puncture with a spring loaded "gun". AB - The study consisted of 89 consecutive patients (mean age = 41.5, range = 16-82, 64 men, 25 women) referred for renal biopsy because of clinical suspicion of renal parenchymal disease. Neither transplant kidneys nor tumour evaluation were included. A biopsy "gun" (Biopty) and 14 (2.0 mm) and 18 (1.2 mm) gauge needles were used with ultrasound guidance. Sixtyseven renal biopsies were guided using a freehand technique 42 using a fixed angle guide attachment. The mean glomerular yield was 9.4 glomeruli. Almost 25% of the 18 gauge needle biopsies (n = 57) had to be repeated and 29.3% of the 14 gauge needle biopsies (n = 75). The yield difference was not statistically significant (Chi-squared = 0.37, p = 0.54). There was no statistically significant difference between the distributions of failure to obtain a significant material for evaluation caused by the biopsy technique used (Chi-squared = 0.08, p = 0.78). When analysing cases of single successful pass the thinner needle produced 6.7 glomeruli (n = 36, SD = 5.08) and the thicker needle 13.8 glomeruli (n = 18, SD = 6.82). No serious complications occurred. PMID- 1439603 TI - Microalbuminuria in obesity. AB - Albumin excretion rate, glomerular filtration rate (GFR) and kidney volume in obese patients and normal-weight controls were compared with body mass index (weight (kg)/height2 (m)) in 17 subjects. Body mass index varied from 21.5 to 48.0, the albumin excretion rate from 2.8 to 17.8 micrograms/min, and the kidney volume from 238 to 468 ml. Body mass index correlated significantly with albumin excretion rate and with kidney volume (p < 0.01), but not with the GFR. Neither the body mass index nor the albumin excretion rate showed any correlation with blood pressure. Albumin excretion rate in obese subjects could be as good an early predictor of complications as it is in patients with diabetes mellitus, and in the elderly. PMID- 1439604 TI - Pretransplant parathyroidectomy in renal failure: effects on bone histology and aluminum deposits during dialysis and after kidney transplantation. AB - Using repeat bone biopsies, we studied whether 1) subtotal parathyroidectomy (PTX) enhances aluminum (Al) deposition in bone and 2) whether pretransplant PTX affects Al removal from bone after kidney transplantation. Twenty-four kidney graft recipients, 10 subjected to PTX 9-44 months prior to transplantation and 14 controls matched for dialysis duration, had bone biopsies taken at transplantation. Serum calcium and parathyroid hormone levels had decreased after PTX in all 10. At transplantation, eroded bone surface was lower in PTX recipients, while extent of Al-stained bone surface and prevalence of symptomatic Al-related bone disease were similar in both groups (PTX: 2/10; non-PTX: 4/14). Hence, PTX did not enhance accumulation of stainable bone Al nor increase prevalence of clinical bone disease during dialysis. Fourteen (7 PTX) recipients with functioning grafts had a second biopsy 12 months after transplantation. Symptomatic Al-related bone disease was cured regardless of pretransplant PTX, and Al-stained surface had decreased in all but one (PTX) recipient. PMID- 1439605 TI - The impact of total unilateral ureteral obstruction on intrarenal angiotensin II production in the polycalyceal pig kidney. AB - Nine pigs with unilateral complete ureteral obstruction were investigated for 15 hours. Obstruction of the ureter resulted in a maximum intrapelvic pressure of 60 cmH2O within the first hour after obstruction, and a gradual decline to 40 cmH2O during the next 15 hours. In 6 pigs both renal veins were catheterized together with the abdominal aorta allowing measurement of the hormonal difference over the kidney. Plasma angiotensin II, plasma vasopressin and plasma atrial natriuretic peptide concentrations were determined. Arterial concentration of plasma angiotensin II gradually increased from 38.7 pg/ml to 252.3 pg/ml. The highest concentrations of angiotensin II were found from the ipsilateral renal vein. From 1 hour after obstruction and onward there was a negative extraction ratio of angiotensin II from the ipsilateral kidney indicating enhanced intrarenal generation of angiotensin II. No difference in vasopressin was found among the sample sites, but a significant reduction in vasopressin from 15.2 pg/ml to 4.9 pg/ml was found from the ipsilateral renal vein during the 15 hours of unilateral ureteral obstruction. Arterial atrial natriuretic peptide concentrations were higher than renal venous levels at all times. Glomerular filtration was immediately reduced to 58%. It is suggested that an increased ipsilateral generation of intrarenal angiotensin II is at least partly responsible for some of the changes in kidney function during acute obstruction. PMID- 1439606 TI - Testicular and cardiac amyloidosis. Case report. PMID- 1439607 TI - Bilateral epididymal sarcoidosis. Case report. AB - A 59-year-old man presented with a four-month history of almost painless bilateral scrotal swellings. Histological examination of a biopsy specimen confirmed sarcoidosis. He was well two months later, the mass had not increased, and he was receiving no treatment. This is the nineteenth reported case to our knowledge, and the eighth with bilateral disease. PMID- 1439608 TI - Septic arthritis of the hip complicating Salmonella psoas abscess. Case report. PMID- 1439609 TI - Uretero-iliac fistula--a rare cause of hematuria. Case report. AB - Fistulation between the ureter and iliac artery is a rare cause of hematuria. Like our case, most of the cases reported so far, originate from traumatic or iatrogenic lesions. This condition should be considered in patients with massive hematuria and underlying predisposing factors. PMID- 1439610 TI - Changes in renal function during the development of hypertension and effects of antihypertensive treatment. A case report. AB - Renal function was serially investigated during the development of hypertension in a 12.8-year-old girl with chronic glomerulonephritis. Clearances of inulin (CIn) and para-aminohippuric acid (CPAH), filtration fraction, and sodium excretion were measured during hydropenia and isotonic saline volume expansion. Blood pressure was initially labile, but after a few years fixed hypertension developed, and antihypertensive treatment with propranolol was started. During the early stages of hypertension, the filtration fraction during hydropenia was reduced, but the natriuresis during volume expansion was normal. When the hypertension was fixed, glomerular filtration rate, CPAH, and filtration fraction were normal, but the natriuresis was exaggerated. Antihypertensive treatment only partially corrected the natriuresis. PMID- 1439611 TI - Phaeochromocytoma--an unusual cause of haematuria. AB - A patient was admitted to hospital because of haematuria. A papillomatous bladder tumor was removed. Histological examination revealed a phaeochromocytoma. Fourteen days postoperatively the urinary excretion rates of catecholamines were elevated but normalized afterwards. Abdominal computed tomography and metaiodobenzylguanidine scintigraphy were normal. No hypertension or characteristic micturitional attacks preceded removal of the tumor. PMID- 1439612 TI - Diagnostic criteria in schizophrenia: accentuate the positive. AB - In a recent article, Andreasen and Flaum (Schizophrenia Bulletin, Vol. 17, No. 1, 1991) argued that greater emphasis should be placed on negative symptoms in the diagnosis of schizophrenia, leading to a less important role for positive symptoms. This article presents a counter-argument to this view. Positive symptoms are common and reliable and therefore highly useful diagnostically. First-rank symptoms, although not specific to schizophrenia, show good discriminability. No other type of symptom or investigative method can make such claims to usefulness. Although positive symptoms do not predict outcome, this is not a necessary function of diagnostic criteria. The predictive power of negative symptoms is, in any case, based largely on studies of patients with chronic disorder. Premorbidly impaired social development may interact with schizophrenia, worsening the prognosis. We believe positive symptoms have always been the essence of psychiatric disorder and should remain so. Increasing the diagnostic weight given to negative symptoms risks restricting the definition of schizophrenia excessively. PMID- 1439613 TI - Clinical services research. PMID- 1439614 TI - Service systems research. PMID- 1439615 TI - Research resources. PMID- 1439616 TI - Disorder of attention in individuals with schizotypal personality. AB - This study was designed to examine disorder of switching attention in normal individuals with schizotypal personality. High scorers on the physical anhedonia (PA) and schizophrenism (SZ) scales of a questionnaire constructed to measure schizotypy were compared with a group of control subjects. A reaction time test was used that required switching attention across or between auditory and visual modalities. It was found that the high PA scores and the high SZ scorers showed a deficit of shifting attention across modalities compared with the control subjects. PMID- 1439617 TI - First person account: my schizophrenia. PMID- 1439618 TI - The Tampere Longitudinal Study on Ageing. Description of the study. Basic results on health and functional ability. PMID- 1439619 TI - Occupational causes of some rare cancers. A literature review. PMID- 1439620 TI - The efficacy of Arthrotec in the treatment of osteoarthritis. AB - In a double-blind study, 455 patients with osteoarthritis were randomly assigned to receive a combination of Arthrotec, 50 mg of diclofenac and 200 micrograms of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 4 weeks. At weeks 2 and 4 of treatment, no significant differences between the treatment groups were noted in changes from baseline on the physicians' and patients' global assessment of osteoarthritis. On a measure of arthritis severity, patients with both arthritis of the hip and knee showed improvement from week 2 to week 4, with no significant differences between treatment groups. PMID- 1439621 TI - The safety of Arthrotec in patients with rheumatoid arthritis or osteoarthritis: an assessment of the upper gastrointestinal tract by endoscopy. AB - Two double-blind comparative studies were conducted to determine the upper gastrointestinal safety of Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol versus 50 mg of diclofenac. In one study, rheumatoid arthritis patients were randomly given Arthrotec or diclofenac 2 or 3 times daily for 12 weeks. Endoscopy was performed before and after treatment. At the termination of treatment, among the 290 patients with rheumatoid arthritis, gastroduodenal ulcers were found in 4% of the Arthrotec-treated patients and in 11% of the diclofenac-treated patients (P = 0.034). In the second study, osteoarthritis patients were randomly given Arthrotec or diclofenac 2 or 3 times daily for 4 weeks. Endoscopy was performed before and after treatment. Among the 329 patients with osteoarthritis, gastroduodenal ulcers were found in none of the Arthrotec patients and in 4% of the diclofenac patients (P = 0.015). PMID- 1439622 TI - Overall safety of Arthrotec. AB - Data from four double-blind studies of the treatment of patients with rheumatoid arthritis or osteoarthritis were combined. For 4 to 12 weeks, 747 patients received Arthrotec, a combination of 50 mg of diclofenac and 200 micrograms of misoprostol, and 754 patients received 50 mg of diclofenac; the drugs were given twice or three times daily. The five most commonly reported adverse events were abdominal pain by 23.2% of the diclofenac/misoprostol patients and 19.8% of the diclofenac patients; diarrhea by 19.9% and 11.3%; nausea by 11.8% and 6.5%; dyspepsia by 11.2% and 7.8%; and flatulence by 8.0% and 3.1%. Other adverse events, reported by similar proportions of both treatment groups, included headache, gastritis, dizziness, vomiting, and constipation. In the diclofenac/misoprostol-treated patients, the abdominal pain and diarrhea were rated mild in 30.6% and 24.3%, moderate in 49.1% and 51.4%, and severe in 20.2% and 24.3%. Serious adverse events occurred in eight of the diclofenac/misoprostol treated patients and in 13 of the diclofenac-treated patients; 12.6% and 10.1%, respectively, were withdrawn from the study because of adverse events. Results of laboratory tests of hepatic and renal function were similar in the two treatment groups. PMID- 1439623 TI - Biopharmaceutical profile of diclofenac-misoprostol combination tablet, Arthrotec. AB - Arthrotec, a combination tablet has been developed that contains 50 mg of diclofenac in an inner core and 200 micrograms of misoprostol in an outer mantle. Both diclofenac and misoprostol are extensively absorbed and their maximum plasma concentrations, but not total availability, are diminished when taken with food. Both drugs have elimination half-lives of less than 2 hours and do not accumulate in plasma after recommended doses. Pharmacokinetic and bioavailability studies of the combination product taken separately and together reveal a high between- and within-subject variability in plasma diclofenac levels, especially when the enteric-coated tablets were given after food; reliable values for peak plasma diclofenac concentration could not be ascertained. No pharmacokinetic interactions between diclofenac and misoprostol were apparent. The bioavailability of diclofenac and misoprostol from the combination tablet was similar to that seen when the two drugs are given separately. PMID- 1439624 TI - The economic consequences of NSAID-induced gastropathy: the French context. AB - The costs of treating gastroduodenal ulcers caused by nonsteroidal anti inflammatory drugs (NSAIDs) are shown to increase the total cost of NSAID treatment to the Assurance-Maladie, the French national health insurance system. This increased cost is termed the iatrogenic cost factor, and is defined as the ratio of the shadow price of an NSAID to its reimbursed cost. The shadow price is calculated from estimates of the incidence of NSAID-induced gastropathies, the cost of the drug, and the hospital and ambulatory costs of treating the gastropathies. The resulting iatrogenic cost factors are estimated as 1.36 for naproxen, 1.48 for sulindac, 1.65 for diclofenac, 1.67 for piroxicam, 2.00 for ketoprofen, and 2.12 for etodolac. PMID- 1439625 TI - Anti-inflammatory efficacy versus gastrointestinal safety: a dilemma resolved? Introduction. PMID- 1439626 TI - The economic consequences of NSAID-induced gastropathy in the United Kingdom and commentary on the article by G. de Pouvourville. AB - The iatrogenic cost factor of treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is defined as the increase in cost resulting from NSAID-induced gastroduodenal ulcers. The iatrogenic cost factor of NSAIDs for the National Health Service (NHS) in the United Kingdom was calculated using the model of de Pouvourville (1992). The cost factor is defined as the ratio of the shadow price of the NSAID to the NHS price. The shadow price is calculated from the incidence of NSAID-induced gastroduodenal ulcers and the costs of treating them and the price of the drugs. The NHS iatrogenic cost factors of 10 NSAIDs were similar to those calculated by de Pouvourville for the French national health insurance system, Assurance-Maladie, and ranged from 1.08 for diclofenac/misoprostol to 2.38 for ibuprofen. PMID- 1439627 TI - Efficacy of Arthrotec in the treatment of rheumatoid arthritis. AB - In a double-blind study, 346 patients with active rheumatoid arthritis were randomly assigned to receive Arthrotec, a combination of 50 mg of diclofenac and 200 *g of misoprostol, or 50 mg of diclofenac; the drugs were given two or three times daily for 12 weeks. At weeks 4, 8, and 12 of treatment, no clinically significant differences between the two treatment groups were noted on measures of joint tenderness, pain, and swelling or on physicians' and patients' assessments of disease severity. PMID- 1439628 TI - Endothelial cell destruction by polymorphonuclear leukocytes incubated with sera from patients with systemic lupus erythematosus (SLE). AB - When normal polymorphonuclear leukocytes (PMN) were incubated with sera from patients with active systemic lupus erythematosus (SLE), a significantly increased cytotoxicity against human cultured vascular endothelial cells (EC), compared with normal control sera, was demonstrated by the standard 51Cr release method. The degree of this cytotoxicity was correlated with the immune complex level in each serum. The cytotoxicity did not correlate with the presence of anti EC antibody. An absorption study with C1q-Sepharose 4B further suggested that the immune complexes are the factor which induce cytotoxicity. A gel fractionation study, however, indicated the heterogenity of the cytotoxic activity, and suggested the possible contribution of other substances including anti-EC, at least in some of the patients. This type of cytotoxicity may initiate the inflammatory process including vascular damage of the disease. PMID- 1439629 TI - Morphological evidence for biological control of urate crystal formation in vivo and in vitro. AB - Urate crystal formation, and subsequent gout, occurs in only a minority of hyperuricaemic subjects indicating that factors other than hyperuricaemia are involved. Biological substances (especially proteins) alter crystal growth in vitro independently of uric acid concentration. Physiological crystal formation, known to be under biological control, is characterised morphologically by uniformity of size and constraint of crystal shape. To determine whether pathological urate crystal formation is influenced by the surrounding biological milieu we examined, using scanning electron microscopy, the morphology of urate crystals formed either in vivo or in vitro. We found morphological evidence of biological control of in vivo urate crystal formation and demonstrated that those characteristics could be induced in vitro by the addition of serum, synovial fluid and certain serum proteins to the growth medium during crystal formation. Urate crystal formation is dependent, not only on the degree of hyperuricaemia, but also on the surrounding biological milieu. PMID- 1439630 TI - Nailfold capillary permeability in psoriatic arthritis. AB - This study is the first report of the permeability status of nailfold capillaries in psoriatic arthritis (PA). "Traditional" nailfold capillary microscopy and intravital fluorescence videomicroscopy were carried out at the nailfold of 13 patients with PA. Twenty five healthy subjects served as controls for nailfold capillary microscopy, and 15 out of these for fluorescence videomicroscopy. The following parameters were assessed: capillary length, apex width, maximum loop width, maximum limb width, loop density, visibility of subpapillary venular plexus, loop tortuosity, transcapillary diffusion, and interstitial concentration at different sites and times of Na-fluorescein given in intravenous bolus. Morphometric analysis of capillaroscopic findings showed a significant increase of loop length (mean +/- SD: 290.1 +/- 73.5 microns) when compared to healthy controls (223.3 +/- 51.9 microns) (P < 0.02). Transcapillary passage of Na fluorescein was homogeneous and symmetric both in PA patients and in controls. Mean transcapillary and interstitial diffusion was not significantly enhanced at the nailfold in PA patients. Our data support the view that PA is not characterized by a specific capillaroscopic pattern and/or significant abnormalities of microvascular dynamics at the nailfold. PMID- 1439631 TI - Validation of a Swedish version of the Arthritis Self-efficacy Scale. AB - The purpose of this study was to test the validity of a Swedish Version of the Arthritis Self-efficacy Scale on two groups of patients: 25 patients with chronic pain and 24 rheumatology patients. Scores on the three subscales of the self efficacy instrument--for controlling pain, for controlling function of daily living activities, and for controlling other symptoms--were correlated with indicators of present pain status and scores on the Multidimensional Health Locus of Control Scales. All correlations were in the direction predicted by self efficacy theory, providing evidence for the construct validity of the scale. In addition the two patient groups differed significantly on the three subscales indicating evidence for the discriminant validity of the instrument. PMID- 1439632 TI - Long-term evaluation of penicillamine or cyclofenil in systemic sclerosis. Results from a two-year randomized study. AB - In a two-year prospective therapeutic trial 13 patients with systemic sclerosis (SSc) were treated with penicillamine, 9 with cyclofenil, and 7 with neither. At entry skin involvement and esophageal, lung, heart, and kidney function did not differ significantly between the groups. Reevaluation after one and two years did not show any significant changes in skin, esophageal, heart, and kidney manifestations, while lung function had slightly improved in both drug-treatment groups. This study thus shows little overall effect of penicillamine and cyclofenil, although both drugs may arrest worsening of pulmonary dysfunction. PMID- 1439633 TI - Sensitivity to UV light during treatment with chloroquine in rheumatoid arthritis. AB - Chloroquine and hydroxychloroquine have long been suspected of causing light sensitivity in patients with rheumatoid arthritis (RA). To gain insight into the effect of chloroquines and ultraviolet (UV) light in RA we have phototested 25 RA patients with and without chloroquine. The thresholds for UVA and UVB did not change upon treatment with chloroquine or hydroxychloroquine. Provocation with high dose UVA and UVB was similar with and without treatment with chloroquine or hydroxychloroquine. Our results have shown that photosensitivity during medication with chloroquine and hydroxychloroquine is uncommon and that there is no need to stop this treatment due to sun exposure. PMID- 1439634 TI - Posterior scleritis related fundal mass in a patient with rheumatoid arthritis. PMID- 1439635 TI - Amyloidosis of juvenile chronic arthritis in Turkish children. PMID- 1439636 TI - Intravenous methylprednisolone therapy in rheumatoid arthritis: a comparative dose study. PMID- 1439637 TI - The prevalence of fibromyalgia and widespread chronic musculoskeletal pain in the general population. PMID- 1439638 TI - Long-term blood flow potentials in sequential internal mammary artery grafts. Exercise thallium scan for myocardial perfusion study. AB - In two groups of patients, coronary artery bypass surgery for angina pectoris included internal mammary artery (IMA) sequential grafts (group I) or single grafts (group II). At postoperative angiography all grafts were patent. In addition, the patients received on average 1.8 vein grafts into other coronary arteries. The mean interval to postoperative follow-up was 9.5 years in group I and 9.7 years in group II. The preoperative incidence of acute myocardial infarction was 44% and 45% in groups I and II. Exercise thallium scan at follow up showed IMA graft-related ischemia in 33% of the patients with sequential graft and in 64% of those with single graft (ns). Our results indicated that sequential IMA grafts functioned at least as well as single grafts and maintained adequate myocardial supply even 10 years postoperatively. Internal mammary arteries are superior graft material and can be recommended both as single and as sequential graft in coronary artery bypass surgery. PMID- 1439639 TI - Surgical treatment of myocardial bridging causing coronary artery obstruction. AB - Nine patients with obstruction of coronary artery blood flow caused by myocardial bridging underwent surgery after failure of medical treatment. The diagnoses were made angiographically at rest or during beta-stimulation. Impaired blood flow was found only in the left anterior descending artery in seven patients and additionally in the diagonal branch in two. The operations, performed with cardiopulmonary bypass consisted of complete dissection of the overlying myocardium. All patients survived the operation. Major intraoperative complications were accidental opening of the right ventricle in two patients. Postoperative scintigraphic and angiographic studies demonstrated restoration of coronary flow and myocardial perfusion without residual myocardial bridges under beta-stimulation. Surgical relief of myocardial ischemia due to systolic compression of intramyocardial coronary arteries can be accomplished with low operative risk and with excellent functional results. PMID- 1439640 TI - Hemodynamic effects of intraaortic versus intravenous protamine administration after cardiopulmonary bypass in man. AB - A hemodynamic study of men undergoing elective coronary artery bypass surgery was undertaken to elucidate the side effects of protamine given into the ascending aorta (group A, n = 16) or into the central venous line (group V, n = 16). After termination of extracorporeal circulation, protamine was infused over 120 seconds, and the hemodynamic profile was continuously recorded. During the first minute, the systemic arterial pressure fell to about 60% of the preprotamine level in both groups, but the hemodynamic changes occurred more rapidly (p < 0.05) in group V than in group A, with maximal pressure drop at 61.7 +/- 2.7 vs 74.4 +/- 4.9 seconds. Following spontaneous restoration of the systemic blood pressure, the pulmonary artery pressure rose considerably in both groups, as did the pulmonary capillary wedge and central venous pressures, reaching higher levels in the intravenous group. The cardiovascular responses were again more rapid in group V than in group A (p = 0.004). The degree of systemic hypotension thus did not benefit from use of the intraaortic rather than the intravenous route for administering protamine. The more pronounced and more rapid pulmonary circulatory changes in the intravenous group suggest that the hemodynamic effects of protamine are initiated in the lungs. PMID- 1439641 TI - Motility studies of the cervical esophagus with intrathoracic gastric conduit after esophagectomy. AB - Gastric emptying, upper esophageal sphincter pressure and intrathoracic gastric motility were studied in esophagectomized patients, ten with a gastric conduit in the posterior mediastinum and ten with a conduit in the retrosternal space. In addition, the clinical state was reassessed more than 6 months after esophageal reconstruction. Gastric emptying, assessed with Tc-99m Sn colloid in a semisolid test meal, did not differ between the two groups. In manometric studies a high pressure zone distal to the upper esophageal sphincter was associated with dysphagia. A high-pressure zone at the anastomosis was found in 60% of the retrosternal group and 20% of the posterior mediastinal group. As regards food intake, the posterior mediastinal route seems to be preferable in esophageal replacement, since it permits more physiologic motility of the conduit. PMID- 1439642 TI - Suture closure versus stapling of bronchial stump in 304 lung cancer operations. AB - Suture closure of the bronchial stump was compared with staple closure after 304 operations for bronchogenic carcinoma over an 8-year period. In 154 cases (112 lobectomies and 42 pneumonectomies) the bronchial stump was closed with interrupted sutures of 000 polyester, and in 150 cases (120 lobectomies and 30 pneumonectomies) an autosuture stapler was used. The time for suture closure ranged from 5-15 minutes, whereas stapling was accomplished uniformly in c. 90 seconds. Bronchopleural fistula developed after suture closure in seven cases (4.5%), but in none after stapling closure. Stapling of the bronchial stump after lobectomy or pneumonectomy for lung cancer is safer and quicker than suture closure, and is recommended as the method of choice. PMID- 1439643 TI - Surgical treatment of stage III non-small cell bronchogenic carcinoma involving the chest wall. AB - Thirty-five patients who had undergone surgery for non-small cell bronchogenic carcinoma with isolated involvement of the chest wall were reviewed. The diagnosis was preoperatively suspected in 80% of cases. En-bloc resection of the invaded chest wall was performed in 25 cases and parietal pleurectomy in ten in which the pleura was easily dissectable from the costal plane. Of the eight patients with major complications in the early postoperative period, six, including the two who died perioperatively, had undergone en-block resection. The 5-year actuarial survival rate was 22% overall and 36% in the patients without lymph node involvement. No significant relationship between survival and type of operation or degree of chest wall invasion was found. Isolated involvement of the chest wall by non-small cell bronchogenic carcinoma does not necessarily contraindicate surgery with curative intent. Parietal pleurectomy is valid in selected cases. Long-term survival depends basically on node involvement. PMID- 1439644 TI - In vitro responses to atrial natriuretic polypeptide in human vessels commonly used as aortocoronary bypass grafts. AB - Vascular effects of atrial natriuretic polypeptide (APII), i.e. the peptide hormone released from the atrial myocardium, were investigated in segments of the human internal thoracic artery (ITA) and saphenous vein (SV) with intact (+E) or injured (-E) endothelium. All segments were subject to several cycles of agonists in order to detect tachyphylactic or facilitatory responses. Opposite, indirect effects on the noradrenaline contracted ITA and SV were obtained in response to APII at a supranormal concentration (50 nM) which had no direct relaxing action on the isolated segments in vitro. In ITA the noradrenaline contractures in subsequent cycles were reduced to 41 +/- 21% (+E) and 28 +/- 9% (-E), but in SV they were enhanced to 211 +/- 115% (+E) and 483 +/- 242% (-E) of those before APII exposure. Thus under in vitro conditions ITA could be indirectly relaxed by APII via tachyphylactic effect on the noradrenaline contracture. SV, on the other hand, was markedly potentiated by APII in its noradrenaline response. In injured endothelium these opposite effects were aggravated. PMID- 1439645 TI - Efficacy of phosphodiesterase inhibitor enoximone in management of postcardiotomy cardiogenic shock. AB - The efficacy of the phosphodiesterase inhibitor enoximone for reversal of severe postcardiotomy low cardiac output syndrome was investigated in 13 cases of cardiogenic shock refractory to conventional treatment consisting of beta adrenergic agonists (n = 13) combined with vasodilators (n = 7), and intra-aortic balloon counterpulsation (n = 5). Following a bolus of 1 mg/kg enoximone, cardiac and stroke volume indices increased from 1.56 +/- 0.27 l/min/m2 and 16.3 +/- 3.3 ml/m2, respectively, to 2.72 +/- 0.67 and 27.8 +/- 7.1 (both p < 0.001). Mean arterial pressure fell, from 77 +/- 11 to 68 +/- 9 mmHg (p < 0.05), as did atrial filling pressures (LAP and RAP), LAP from 21.3 +/- 5.5 to 15.9 +/- 2.9 and RAP from 16.6 +/- 2.3 to 13.7 +/- 2.1 mmHg (both p < 0.01). The heart rate rose by only 5%. Enoximone therapy was maintained by a continuous infusion (5-7.5 micrograms/kg/min) for 40.6 +/- 8.6 hours (range 14-92). All hemodynamic parameters remained stable throughout treatment. Six patients died of sepsis and/or multiorgan failure but seven were discharged from hospital. Enoximone thus improved hemodynamic performance significantly in cardiogenic shock after open heart surgery. It also has proved valuable in cardiac failure when conventional therapy was unsuccessful. PMID- 1439646 TI - Effect of acid-base management with or without carbon dioxide on plasma phosphate concentration during and after hypothermic cardiopulmonary bypass. AB - Variations of the phosphate concentration in plasma were studied in two groups of 12 patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass (CPB). Management of the acid-base status differed between the groups, according to whether or not carbon dioxide was added to the anesthetic gas mixture during hypothermia ('pH-stat' vs. 'alpha-stat' mode) following correction vs. no correction of pCO2 and pH for body temperature. Phosphate variations throughout the study were mostly within normal limits. From the start to the end of CPB, the mean rise in phosphate levels was 70% in the pH-stat group and 37% in the alpha stat group (p < 0.001). During 3 hours after CPB, the phosphate values continued to rise by a mean of 25% in the alpha-stat patients, but fell by a mean of 3% in the pH-stat patients (p < 0.001). Such different phosphate patterns during and immediately after CPB may reflect profound metabolic disturbances and may be related to the altering effects of CO2 addition and respiratory acidosis on intracellular metabolic activity and phosphate homeostasis. PMID- 1439647 TI - Successful surgical management of rupture of the left ventricle and interventricular septum due to blunt chest trauma. Case report. AB - In a 35-year-old man blunt chest trauma caused rupture of the free wall of the left ventricle and the interventricular septum. Emergency pulse Doppler-2D echocardiography confirmed the clinical suspicion and immediate surgical repair was successfully undertaken. This appears to be the first reported case of survival after surgery for such combined cardiac rupture. PMID- 1439648 TI - Carcinosarcoma of the lung with gastrointestinal metastasis. Case report. AB - An unusual case of carcinosarcoma of the lung with metastasis to the gastrointestinal tract causing intussusception is presented. The clinical, radiologic and histopathologic features are reviewed with reference to relevant literature. PMID- 1439649 TI - Dimensions of the heart and great vessels in normal children. A postmortem study of cardiac ventricles, valves and great vessels. AB - Knowledge of normal heart dimensions is often needed in the planning of cardiac surgery in children. Attempts to define 'normal' have so far given varied and somewhat controversial results. The purpose of this study was to determine normal values for all heart measurements of clinical importance in children. Special interest was focused on the relationship between the diameters of the right and the left pulmonary artery (RPA abd LPA) and the descending thoracic aorta (DTA), defined as RPA/DTA+LPA/DTA, which is widely used in evaluating the feasibility of certain pediatric cardiac operations. The normal curve of this ratio during growth has not previously been presented in the literature. The observed data provide reliable normal values for the diameters of the great vessels and valves and the ventricular volumes of the heart. PMID- 1439650 TI - Ductus arteriosus in pulmonary atresia with and without ventricular septal defect. Anatomic and functional differences. AB - The pulmonary circulation is dependent on the ductus arteriosus in all patients with pulmonary atresia and intact ventricular septum and in some with pulmonary atresia and ventricular septal defect (tetralogy of Fallot type). To assess the time of ductal closure in these two patient categories, we compared the ages at first operation in 58 patients with pulmonary atresia and intact ventricular septum and 32 with pulmonary atresia and septal defect. The age distribution differed significantly between the groups. Whereas 90% of the children with intact ventricular septum required surgery in the first week of life, 50% of those with ventricular septal defect underwent surgery after the first month and 25% after the third month. The previously described and now confirmed anatomic differences of ductus arteriosus or different levels of endogenous prostaglandins may explain persistent patency of the ductus in pulmonary atresia with ventricular septal defect. The phenomenon may have important clinical implications regarding the timing and choice of surgical procedure. PMID- 1439651 TI - Open-heart surgery in patients requiring chronic hemodialysis. AB - The management and outcome of open-heart surgery in 31 patients requiring chronic hemodialysis because of end-stage renal failure are reviewed. The reasons for surgery were coronary artery disease (20 cases), mitral valvulopathy (5, including 3 with tricuspid insufficiency), aortic valvulopathy (5, including 2 with coronary artery disease) and perforation of an aortic aneurysm into the left upper lung lobe. Surgery was elective in all but the last case. Apart from double venous cannulation to avoid potassium overload after cardioplegia, and hemofiltration in the extracorporeal circulation permitting removal of 1,500 2,000 ml fluid during bypass, procedure was routine. Postoperatively fluids were restricted and serum potassium levels were not allowed to exceed the known preoperative maximum. Four patients required catecholamine support for 3-10 hours. Thirty were weaned from the respirator after 8-41 (mean 16) hours. The one perioperative death was due to complications associated with post-bypass administration of protamine. Dialysis was restarted 20-69 (mean 32) hours postoperatively. With appropriate management of fluid balance and potassium, open heart surgery in dialysis-dependent patients need not carry heightened risk. PMID- 1439652 TI - Problems and perspectives in the identification of new occupational carcinogens. AB - Occupational studies have played a major role in the identification of chemical carcinogens. There still remain, however, substances and occupations that deserve further evaluation. The more careful control of potentially hazardous exposures in most developed countries has necessitated a change in the conduct of epidemiologic investigations. The lowering of exposures and the lack of a simple correspondence between specific exposures and one or a few jobs underscores the need for careful reconstruction of historical exposures. The most successful reconstructions will include the integration of monitoring data, historical information on work histories and work practices, and use of biochemical markers. PMID- 1439653 TI - Lung cancer mortality among workers in the European production of man-made mineral fibers--a Poisson regression analysis. AB - One hundred and eighty-one lung cancer deaths among workers during 301,085 person years in European man-made mineral fiber production between 1930-1955 and 1982 were analyzed according to Poisson regression models including age, calendar period, country, and exposure variables. Time since first employment was the variable most strongly associated with lung cancer risk in both the rock-slag wool and glass wool subcohorts. Workers in the early technological phase were at higher risk than those in other categories, particularly in rock-slag wool production. No clear trend with duration of employment was suggested. No major changes occurred in the interpretation of the results when workers with less than one year of employment or less than 20 years since first exposure were excluded. The original results, based on analyses for standardized mortality ratios, were confirmed, and workers with a short duration of employment or a short time since first employment did not need to be excluded from the analysis. PMID- 1439654 TI - Oral, pharyngeal and laryngeal cancer as a cause of death among Swiss cooks. AB - In an analysis of Swiss mortality data (1979-1987) excess mortality due to oral, pharyngeal and laryngeal cancer was found among cooks, and the rate was very high in the age group < 55 years. The peak number of cases was observed among cooks in the age category 45-49 years. In the standard population the highest number of such deaths was observed between 65 and 69 years of age. The numbers of alcohol related causes of death were also elevated among the cooks, while the numbers of smoking-related deaths were not. Although the dominant role of combined alcohol and tobacco consumption for the development of oral, pharyngeal and laryngeal cancer has been confirmed by many studies, other factors (eg, volatile carcinogenic compounds formed during the cooking process) may contribute to the excess mortality from oral, pharyngeal and laryngeal cancer among cooks. The question of the relevance of such factors will have to be answered by further studies. PMID- 1439655 TI - Work-related electrical fatalities in Australia, 1982-1984. AB - Work-related electrical fatalities were studied as part of a larger investigation into all work-related fatalities in Australia in the period 1982-1984. The 95 electrical fatalities (all men) represented an incidence of 0.49 per 100,000 persons (0.79/100,000 men) in the employed civilian labor force during the study period. Electricity was the fifth highest cause of work-related fatalities in Australia and resulted in 10% of all workplace deaths. Ninety-four percent of the workers were performing their usual tasks at the time of their death, and 38% of them were doing work of an electrical nature at the time. The greatest number of deaths occurred on farms and nonconstruction industrial sites, with overhead powerlines as the main source of current. Better placement of overhead powerlines, improved worker awareness of electrical hazards, and the use of residual current devices would probably have prevented most of the deaths. PMID- 1439656 TI - Fecundity and the use of video display terminals. AB - The association between prolonged waiting time to pregnancy and the use of a video display terminal (VDT) was investigated among commercial and clerical employees in Denmark. Information on 24,352 pregnancies was obtained through register linkage with two national registers. A random sample of 2252 pregnancies was drawn, and the women were asked for information on waiting time to pregnancy, occupational exposures, and life-style factors. The overall exposure to a VDT indicated a slightly increased association with prolonged waiting time to pregnancy. The relative risks for waiting more than one year were 1.23, 0.77, and 1.61 for the women who worked with a VDT for 1-10, 11-20, and > or = 21 h per week, respectively. Only the last relative risk was statistically significant. The results could be explained by methodological shortcomings such as recall bias or confounding by alternative factors that might affect time to pregnancy, or simply by the lack of statistical power. PMID- 1439657 TI - Menstrual-cycle characteristics and work conditions of workers in poultry slaughterhouses and canneries. AB - The food and agriculture industry employs 14.6% of the female industrial work force in France. Workers are exposed to a variety of environmental and organizational constraints (eg, irregular schedules, cold, uncomfortable postures, repetitive movements). In 1987-1988 a medical examination and questionnaire were administered to 726 workers with menstrual periods in 17 poultry slaughterhouses and six canning factories. Anomalies (irregular cycles, amenorrhea, long cycles) during the previous year were associated with work conditions. After adjustment for relevant nonoccupational variables, irregular cycles were significantly related to schedule variability and cold exposure, amenorrhea was associated with cold exposure, and long cycles with schedule variability. Other parameters such as repetitive work, standing posture, lifting weights, job satisfaction, and hours of domestic work were not associated with cycle anomalies. Cycle anomalies may be a useful indicator of occupational effects on female reproduction, analogous to the use of sperm parameters to warn of effects on male workers. PMID- 1439658 TI - Knee disorders in carpet and floor layers and painters. AB - In an evaluation of the effect of kneeling work on the knees, 168 actively working carpet and floor layers and 146 house painters were examined with the aid of a questionnaire, a clinical examination, and radiography. Reported knee pain, knee accidents, and treatment regimens for the knees were more common among the carpet and floor layers than among the painters. Radiographic changes of the tibiofemoral joint were noted equally in the two occupational groups, but osteophytes of the patella were more common among the carpet and floor layers than among the painters. In a multivariate analysis, the determinants of osteophytosis of the knee were age, occupation, knee accidents, and smoking, and osteophytosis may be due to more frequent workbreaks from kneeling postures among smoking workers. This study indicates that kneeling work increases the risk of knee disorders and such radiographic changes that might be an initial sign of knee degeneration. PMID- 1439659 TI - Biological monitoring of occupational exposure to low levels of benzene. AB - To obtain reference values for the biological monitoring of benzene, the kinetics of benzene were studied in volunteers. Benzene in blood and expired air could easily be followed until the next morning after a 4-h exposure to a benzene concentration of 10 cm3.m-3. Even after exposure to 1.7 cm3.m-3 the benzene levels in the morning blood and expired air samples differed from those in unexposed subjects. One hour after exposure to 10 and 1.7 cm3.m-3 the mean levels of benzene were 238 and 25 nmol.l-1 in blood and 13.2 and 2.5 mumol.m-3 in exhaled air, respectively. It was concluded that, at high benzene levels (approximately 10 cm3.m-3), samples collected 16 h after exposure reflect the body burden of benzene, while at low exposure (< 1 cm3.m-3) samples collected 1 h after exposure may be used to estimate the exposure over the preceding few hours. Exposure to benzene from smoking is a potential confounder in estimating occupational exposure to low levels of benzene. PMID- 1439660 TI - Tetanus caused by occupational accidents. AB - The role of occupational accidents as a source of tetanus is poorly known. In Finland, during the period 1969-1985, 28 (26%) of the 106 cases of tetanus were caused by occupational accidents, 16 of which occurred in agriculture and forestry. Twenty-one of the patients were men and seven were women. The mean annual incidence of tetanus was 1 per 100,000 occupational accidents during the study period. The cases were concentrated in summer and autumn. Most of the primary injuries were minor, 61% of the injuries occurring in the hands and fingers. Forty-three percent of the patients had not been immunized against tetanus, and 46% were unaware of their state of immunization. The systematic immunization of the population against tetanus is important because the disease is often caused by slight injuries not requiring treatment by health care personnel. This need is emphasized for work in agriculture, forestry, and other branches in which contact with soil or animals occurs. PMID- 1439661 TI - Severe farmer's lung following a workplace challenge. AB - A severe attack of farmer's lung developed in a dairy farmer after a workplace challenge. The patient showed full recovery after corticosteroid therapy. If a workplace challenge is considered necessary in the diagnosis of farmer's lung, care should be taken to avoid unnecessarily heavy exposure to the offending antigens. PMID- 1439662 TI - Carcinogenicity of occupational exposures to mists and vapors from strong inorganic acids, including sulfuric acid, and hydrochloric acid. PMID- 1439663 TI - Carcinogenicity of exposures to 1,3-butadiene. PMID- 1439664 TI - The scanning probe microscope. AB - Scanning probe microscopy has evolved into a powerful tool since its inception in 1982. The scanning probe microscope has found applications in metrology, spectroscopy, and lithography. We will review the background of the technology, discuss the different types of scanning probe microscopes including the scanning tunneling microscope and the scanning force microscope, and present many of the applications for the instrument. PMID- 1439665 TI - Methods for the study of calcium oxalate crystallisation and their application to urolithiasis research. AB - Many methods have been used to study calcium oxalate crystallisation. Most can be characterised by changes in supersaturation during the experiment, which may increase, remain constant or decay. Their ability to quantify various aspects of crystallisation often reflects the extent to which nucleation, growth and aggregation can be measured independently, when two or three of these processes may be occurring simultaneously. The mixed suspension, mixed product removal technique reaches a steady state supersaturation, is a good model for intrarenal crystallisation and allows both growth and nucleation rates to be measured. Using 92% urine and comparing control urines with samples from recurrent stone formers no difference in growth rates was found but the controls had higher nucleation rates (p = 0.003) and lower supersaturations (p = 0.001). In parallel crystallisers running simultaneously, heparin or hyaluronic acid addition to 92% urine was studied. Both macromolecules increased growth rates, decreased nucleation rates and increased supersaturation (p < 0.05). The steady state supersaturation achieved in this system may be an important determinant of stone forming potential. The ability to reach a lower urinary supersaturation by increased nucleation may be a crucial protective factor distinguishing non stone formers from stone formers. PMID- 1439666 TI - A stimulus timing device for capturing fast physiologic events by quick-freezing. AB - A timing device was designed that, in conjunction with an impact type of quick freezing apparatus and an externally-triggerable stimulus generator, allows the application of an electrical stimulus to a muscle preparation at a selected time interval before quick-freezing and the measurement of the interval with submillisecond precision. This is needed for stopping fast physiological events in calcium release and excitation-contraction coupling and allows studying the morphological parameters (by freeze-fracture and freeze-substitution) and elemental distributions (by x-ray microanalysis) as a function of time after stimulation. The device should be adaptable for use with most equipment designed for quick-freezing electrically excitable tissue by impact on a cold solid surface. PMID- 1439667 TI - Scanning X-ray microanalysis of microcarrier cultured endothelial cells: elemental changes during the transition to confluency and the effect of ionophore A23187. AB - Porcine endothelial cells were grown on microcarrier beads and examined by scanning electron microscopy (SEM) at various times after initiation of culture. Total cell coverage on the bead surface varied from mean values of approximately 7% (3h) to 80% (96h). Beam penetration into the subcellular matrix presents a major problem with SEM X-ray microanalysis of microcarrier cultured cells and necessitates the use of an accelerating voltage not exceeding 10kV. At this voltage and below, X-ray contribution from elements present in the microcarrier bead has minimal effect on the determination of cell elemental levels. Washing the cells with 0.15M sucrose was the least perturbing of the rinsing techniques investigated, removing surface culture medium but not internal diffusible ions. X ray microanalysis revealed detectable levels of Na, P, S, Cl, K and Ca in the cells, with well-marked changes from initial attachment to confluency. The level of K decreased from approximately 1.0% at 3h to 0.4% at 24h, with a corresponding decrease in the K/Na ratio. This unexpectedly low level of K was invariably observed after 24h, and is a genuine feature of established microcarrier culture. The effect of ionophore A23187 was determined at the 3h culture stage, and resulted in significant increases in the concentration of divalent cations (Mg2+, Ca2+), monovalent ions (Na+, Cl-) and a decrease in the level of K+. PMID- 1439668 TI - Electron probe microanalysis of the otolithic membrane. A methodological and quantitative study. AB - The effect of tissue preparation on calcium and potassium weight percent in the otoconial layer in the utricle and saccule was studied in four groups of OF1 mice with electron probe X-ray microanalysis. Glutaraldehyde and freeze-drying, glutaraldehyde and air-drying, air-drying, and cryo-fixation and freeze-drying were compared. Ca and K changed significantly in the utricle depending on the method used (P < 0.001), and K changed significantly in the saccule (P < 0.001). We chose cryo-fixation with freeze-drying for the quantitative analysis of the otolithic membrane because this method provided the highest values of Ca and K with minimum loss of Ca and K. Microcrystalline salt standards mounted on scanning electron microscopy holders were used for the quantification of Ca and K by the peak-to-local-background (P/B) ratio method. The P/B ratio in standards with reproducible results, when plotted against weight percent, gave a straight line for Ca (r = 0.99, P < 0.001) and K (r = 0.98, P < 0.001). The Ca and K weight percent in otoconia showed similar frequency distributions in the utricle and saccule. PMID- 1439669 TI - Microwear and striae of Retzius of canines of the wild Japanese monkeys (Macaca fuscata). AB - This is a description of microwear and striae of Retzius of canine teeth of wild caught female Japanese monkeys (Macaca fuscata) from Oita Takasakiyama, Kyushu. Micrographs were taken of high resolution casts using a scanning electron microscope (SEM). Before the casts were made, the diet of the captive monkeys was water-softened for three or four days. This softened diet probably added little wear to the surfaces of the teeth. These animals are part of a sample used in a previous report published in this journal. Others have observed that wild Japanese monkeys eat hard foods (such as grasshoppers, cicads etc.) in the summer season. They also bite the hard bark of trees in order to obtain soft parts of buds in the winter season. The author previously reported that the wild female Japanese monkeys from Oita Takasakiyama showed many thick striations and large pits on the occlusal surfaces of the second mandibular molars, and noted that these microfeatures categorized these samples in the group of hard-object feeders as defined by Teaford. In this study canine teeth are examined. Three were heavily worn, exposing patterns related to the structure of the enamel. Two canines had prism relief on the heavily worn surfaces. Some of the relief seem to be related to the striae of Retzius. These features may be ascribed to excessive grinding (bruxism). These findings are presented as direct evidence of the effect feeding behavior has on the canine teeth of wild Japanese monkeys. PMID- 1439670 TI - Arthropathies associated with basic calcium phosphate crystals. AB - Basic calcium phosphate (BCP) crystals refer to a family of crystals including partially carbonate substituted hydroxyapatite, octacalcium phosphate, and tricalcium phosphate. These crystals have been found in and around joints and have been associated with several forms of arthritis and periarthritis. Identification of BCP crystals remains problematic because of the lack of a simple, reliable analytic procedure. Methods currently in use include alizarin red S staining, labelled diphosphonate binding, scanning and transmission electron microscopy with energy dispersive X-ray microanalysis, X-ray diffraction, and atomic force microscopy. Periarthropathies associated with BCP crystals include calcific tendinitis and bursitis. Intra-articular BCP crystal deposition is common in osteoarthritis, often found together with calcium pyrophosphate dihydrate crystals. Uncommon conditions in which BCP crystals are found include destructive shoulder arthropathies, acute inflammatory attacks of arthritis, and erosive arthritis. Secondary deposition of BCP crystals has been observed in chronic renal failure, in patients with "collagen vascular" diseases, following neurologic injury and after local corticosteroid injection. PMID- 1439671 TI - Functional and morphological studies of mitochondria exposed to undecagold clusters: biologic surfaces labeling with gold clusters. AB - This study reports morphological and functional alterations observed in respiring isolated mitochondria when they are exposed to nonpenetrating, positive electrostatically charged synthetic undecagold clusters. Modification of the undecagold clusters positive charges change or prevent the functional effects and the binding to the outside surface of the mitochondria. The mitochondrial functional alterations are dependent on the oxidative phosphorylation capacity of the isolated organelles. The results of these experiments indicate that artificial undecagold may be useful to explore the molecular mechanisms of biological energy transducers which require electric charges separation, ionic fluxes, and electric surface properties. PMID- 1439672 TI - The use of organ cultures to study vessel wall pathobiology. AB - Organ culture of the vessel wall is an useful in vitro method to study vascular cell biology. The intact vessel allows for the study of cell-cell and cell substratum interactions including the structure and function of the vessel wall matrix. Long term organ cultures of porcine aorta show that neointimal formation is due primarily to cell proliferation of pre-existing intimal smooth muscle cells. Neointimal formation in these cultures is more pronounced in the presence of an endothelium that is turning over. In endothelial wound repair studies, the endothelium of the organ culture shows some important differences when compared to tissue culture studies in monolayer culture. Thus, vascular organ cultures can be successfully used to study vessel wall biology in health and disease. PMID- 1439673 TI - Three-dimensional characterization of dense bodies in contracted and relaxed mesenteric artery smooth muscle cells. AB - We have previously shown that dense bodies are not the static planar simple ovoidal structures they appear to be in thin sections. In this report, we present three-dimensional reconstructions from consecutive serial thin sections through shortened and non-shortened large mesenteric artery cells. Profiles of the cell surface, membrane dense bodies, and cytoplasmic dense bodies were reconstructed from consecutive thin sections and the distribution, size, shape, and spatial relationships among these components was examined. Within the cell, membrane dense bodies are numerous and occupy approximately 10% of the cell volume. Membrane dense bodies can attach to the cell surface laterally, obliquely or normally. An individual membrane dense body can be continuous over more than 2 microns of cell depth and can change shape throughout its depth. On cell shortening, many membrane dense bodies assume a crenated shape. Compared to membrane dense bodies, cytoplasmic dense bodies are smaller in all dimensions and occupy about 2% of the cell volume. In shortened cells, cytoplasmic dense bodies appear to cluster into groups. This redistribution of cytoplasmic dense bodies may be related to the reorganization of contractile units when the cell shortens. PMID- 1439674 TI - Early effects on the morphology of mouse small intestine of single or combined modality treatment with hyperthermia and X-irradiation. AB - This study describes the effects of hyperthermia and X-irradiation on the morphological appearance of normal, at risk tissues in the ileum of the mouse. The early morphological effects 1 day after a combined modality treatment are compared with those due to either hyperthermia or X-irradiation given alone. The response was assessed qualitatively and semiquantitatively using scanning electron microscopy and a villous scoring technique. Early post-irradiation effects on topography did not differ significantly from those observed after small intestine exteriorisation without treatment. The villous scores for the combined modality treatments reflected greater damage than would be expected from the sum of villous scores for each modality treatment on its own. This suggests that the combined modality treatment had a synergistic or enhancing effect. A 4 hour time interval between the two treatments did not seem to reduce the enhancing effect. Further studies are required to investigate the effects of fractionated combined treatment. PMID- 1439675 TI - Morphological study of gastric lesions developing in the rat under several damaging conditions: modifications induced by pretreatment with zinc acexamate. AB - Lesions developing in the gastric mucosa of the rat after exposure to different gastric damaging agents (100 mg/kg aspirin, and 70% or 100% ethanol) were assessed by scanning electron microscopy. The severity of the lesions was quantified according to morphological criteria. Modifications in the severity of these lesions induced by pretreatment with zinc acexamate were also analyzed. The scanning electron microscope revealed that with the exception of absolute ethanol, which caused distinctive morphological features, lesions found under the different experimental agents shared a common pattern of progression. Ultrastructural lesions on surface epithelial cells preceded further alterations of parietal cells. After the integrity of the epithelial cells was lost, detachment of the parietal cells occurred, probably, through peptic digestion of the connections between cells and their extracellular matrices. Pretreatment of animals with zinc acexamate increased the presence of mucus on the gastric surface and significantly prevented the progression of lesions towards the severest stages. Ultrastructural damage of surface epithelial cells was not influenced by this treatment, but detachment of damaged cells was clearly diminished. These data confirm the protective effect of zinc acexamate against gastric aggressions. Moreover, our studies confirm the notion that mucus secretion and maintenance of continuity on the gastric lumen by surface epithelial cells is of critical importance in preventing the gastric damage induced in these experimental models. PMID- 1439676 TI - Appearance of venous sphincters in the pulmonary microvascular bed of normotensive and spontaneously hypertensive rats. AB - The appearance of pulmonary venous sphincters was studied in normotensive and spontaneously hypertensive rats using scanning electron microscopy of microvascular corrosion casts and transmission electron microscopy of tissue sections. Vascular casts were prepared either after lavage with Tyrode solution or after glutaraldehyde prefixation. Pronounced pulmonary venous sphincters were more frequently identified in spontaneously hypertensive rats as compared to corresponding circular indentations in normotensive rats. Tissue sections established venous sphincters in hypertensive animals as consisting of multiple layers of smooth muscle cells in the venous walls. We did not observe any autonomic nerve terminals in close proximity to these bundles of smooth muscle cells. The effect of various casting procedures on the appearance of venous sphincters is discussed. It is concluded that glutaraldehyde prefixation is an appropriate method to demonstrate sphincter functioning, because it causes deepening of sphincter indentations. Pulmonary vascular sphincters are thought to be governed by blood-born substances, vasoactive metabolites, or by tension of oxygen and carbon dioxide. Venous sphincters may influence microvascular flow in general and probably substitute for venous valves in the pulmonary vascular bed where valves are missing. PMID- 1439677 TI - Luminal constrictions on corrosion casts of capillaries and postcapillary venules in rat exocrine pancreas correspond to pericyte processes. AB - The rat exocrine pancreas was studied as a model to demonstrate morphological features of different types of capillaries, using scanning electron microscopy of vascular corrosion casts and transmission electron microscopy of tissue sections. Two types of capillaries were discerned. The first type represents less undulated, slender, straight capillaries with numerous, shallow, circular or semilunar furrows on its cast's surface. In tissue sections, this type probably corresponds to non-fenestrated capillaries. The numerous grooves on its cast correspond to pericyte processes beneath the endothelial lining. The second type comprises capillaries of an undulated course and variable diameter with less numerous furrows. In addition, these casts showed circumscribed, smooth surfaced bulging areas defined by the grooves described. In tissue sections, this type probably corresponds to fenestrated capillaries, the bulging areas on its cast correspond to fenestrated regions of the endothelium. Fenestrated areas of capillary endothelium are less reinforced; pericyte processes are not present beneath these regions in tissue sections. The hypothesis that pericyte processes are responsible for surface indentations on capillary casts was supported by observations on postcapillary venules. Casts of these vascular segments showed also numerous circularly running furrows. Accordingly, the wall of postcapillary venules is provided with pericytes while smooth muscle cells are missing. PMID- 1439678 TI - Vascular anatomy of the pig kidney glomerulus: a qualitative study of corrosion casts. AB - Pig kidney glomerular vascular anatomy was studied by scanning electron microscopy of vascular corrosion casts. A generalized vascular architecture is presented to describe the pig kidney glomerulus based upon the observation of 3,800 vascular cast glomeruli. The relative simplicity of the pig glomerular vascular architecture has allowed the characterization of different vascular segments more completely than has been possible in other mammals. Based upon relationships to the afferent arteriole, a nomenclature and definition of primary, secondary, tertiary and anastomotic vessels is proposed for the distributing vessels comprising the glomerular tuft. The existence and formation of a large central hemispheric vessel deep within the confines of a glomerular hemisphere is micrographically documented. Micrographic evidence is presented supporting the formation of the single efferent arteriole by the merging of two central hemispheric vessels within the confines of the glomerular tuft. Failure of the merging of these two vessels may result in multiple efferent arterioles. PMID- 1439680 TI - [Percutaneous endoscopic gastrostomy in the rehabilitation of neurological disorders]. AB - Chronic enteric alimentation is preferred to parenteral nutritional support not only during intensive care but also during rehabilitation in severe neurologic disorders such as brain injury and high tetraplegia. As the long-term placement of nasogastric tubes has several disadvantages and undesirable side effects, we chose the nonoperative endoscopic technique for placement of a transdermal gastric feeding tube. PEG was performed in 40 patients with neurologic conditions associated with impaired swallowing or repeated aspiration problems: 20 patients with CNS trauma, 13 patients with high tetraplegia and 7 patients with severe neurologic disease of the CNS. The procedure used was that described by Gauderer and Ponsky. It was performed under local anesthesia in the majority of cases and under intravenous sedation in all cases. Technical problems practically did not occur, while minor complications were seen in 15% of the patients treated and major complications in 2.5%. Because of the high rate of peristomal wound infections despite systematic antibiotic prophylaxis, it was assumed that percutaneous infections could be secondary to contamination of the transcutaneous wound with oropharyngeal bacteria and local disinfection of the mouth with betadine has now been started before the procedure. Percutaneous endoscopic gastrostomy is a relatively safe (morbidity of less than 10%), very practical and cost-effective technique. It is well tolerated by the patients in whom swallowing mechanisms are impaired, affords advantages in regard to nursing care and should therefore belong to the standard therapeutic procedures in neurologic rehabilitation. PMID- 1439679 TI - [Heart contusions: pathological findings and clinical course]. AB - After blunt chest trauma, myocardial contusion is frequently suspected, but diagnostic criteria are difficult to define and commonly accepted recommendations for duration and form of patient monitoring are lacking. We therefore conducted a retrospective review of the hospital records of 50 consecutively hospitalized patients with the diagnosis of myocardial contusion after blunt chest trauma, and analyzed the pathological laboratory, ECG and echocardiography findings as well as the associated injuries and cardiac-related complications. The average injury severity score was 25 +/- 8. Initially 98% of the patients were hemodynamically stable. In 90% there were abnormal enzyme levels consistent with myocardial injury. Typically, the maximum level of CPK-MB, LDH and CPK-MB/CPK (MB-fraction) was found initially and these values declined rapidly. The MB fraction normalized within 8 hours. In 32% of the patients there were the following ECG changes consistent with myocardial contusion transient: ventricular tachycardia (12%), ST/T changes (12%), complete right bundle branch block (10%), atrial fibrillation (4%), first degree AV block (2%). The episodes of ventricular tachycardia were registered within the first 24 hours; in 5 of these 6 patients the admission ECG was normal. An echocardiography was done in 64% of the patients and in 37% showed either a pericardial effusion, regional wall motion abnormalities, a pneumopericardium or an intramyocardial hematoma in the free wall of the right ventricle. One patient died of multiorgan failure during this hospitalization. There were no sudden cardiac deaths. The diagnosis of myocardial contusion is vital in unstable patients but also very important in hemodynamically stable patients, despite its low morbidity. The minimum program we recommend for diagnosis and monitoring should include enzyme levels (CPK, CPK-MB) and ECG controls. Echocardiography may be necessary as well. If during the initial compulsory 24 hour monitoring of ECG and hemodynamics no complications occur, further monitoring is not necessary. PMID- 1439681 TI - [Rubella epidemiology in military recruit schools]. AB - In 1986, at the start of their training, 6877 male recruits were screened for the presence of anti-rubella IgG antibodies. 595 (9%) were seronegative. Of the latter group, 475 (80%) were retested in the week prior to discharge. During their four months of training, 113 (24%) exhibited seroconversion which proved acquisition of a rubella virus infection during the period of service. A clinical diagnosis of rubella was established in 15 (13%) of the persons with seroconversion. Catarrhal symptoms were present in half of those infected, whereas 41 (36%) did not report sick, suggesting a subclinical course of infection. Rubella is hardly a problem for the military in Switzerland. However, outbreaks such as the ones reported may have implications for the epidemiology of rubella in the general population, and hence should be taken into account in the planning of programs attempting to eliminate rubella virus infections. PMID- 1439682 TI - [Intellectual and neurological development of 9-15-year-olds who were born as at risk neonates]. AB - This retrospective study deals with 296 children born between 1, Jan. 1974 and 31, Dec. 1980, who had been hospitalized as newborns at the Department of Pediatrics of the University of Berne and who had been considered at risk for abnormal psychomotor development because of well defined perinatal risk factors. Their psychomotor development had first been evaluated in the first months and years of life at the Cerebral Palsy Centre at Berne. In 1989, when the children were 9-15 years old, their neuro-intellectual development was investigated through a questionnaire sent to the families dealing with the subsequent psychosocial and scholastic course. In the CP-Centre, at a median age of 10 and mean age of 26.4 months, 247 (83.5%) of the children had been discharged with the finding of normal psychomotor development, 25 (8.4%) had been considered to show questionable findings and 24 (8.1%) to show obvious abnormal psychomotor development. On the basis of the answers to the questionnaire (median age 11 8/12, mean age 11 10/12 years; 62% return rate), 39.3% of the children had had no further problem, and 57.4% had used special support such as speech therapy or educational consulting and/or had had school problems. 3.3% showed distinct learning disabilities. More than 90% were attending a normal public school. This corresponds to the attendance in the general population. However, fewer children were in higher schools. To investigate whether the judgement in the first months and years (CP-Centre) of life corresponded to the further development (questionnaire), a subpopulation was specially evaluated in addition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439683 TI - [Hypoglycemia and multiple myeloma]. AB - We report the case of a 78-year-old patient with recurrent attacks of severe fasting and late postprandial hypoglycemia, whose plasma showed highly elevated concentrations of immunoreactive insulin evidenced by high titers of spontaneous insulin and proinsulin-binding antibodies. Insulin autoimmune syndrome was diagnosed. Further investigations revealed a multiple myeloma of the kappa-light chain type. The monoclonal insulin-binding antibodies were characterized as IgG2 subclass and were identical with the paraprotein, thereby confirming that the insulin-binding antibodies were in fact produced by the myeloma. Together with initial symptomatic treatment, plasmapheresis was performed repeatedly to reduce the antibody pool. Subsequently octreotide therapy proved successful. The underlying myeloma was treated by chemotherapy. PMID- 1439684 TI - [Neuroradiology of the spinal cord]. AB - In recent years MR has assumed a central and key role in neuroradiological evaluation of the spinal cord. Because of its noninvasiveness and high sensitivity in the detection of intramedullary lesions, it represents the method of choice today for the work-up of acute, chronic and traumatic myelopathies. The main limiting factor of MR is its rather low specificity. For this reason the clinical history as well as the neurological and laboratory findings continue to be of major importance in arriving at a definite diagnosis. The method is contraindicated in patients with pacemakers or other intracorporeal paramagnetic devices. It is relatively contraindicated in claustrophobic patients. In these cases MR should be replaced by myelography or CT-myelography. For the diagnosis of vascular diseases of the spinal cord, specifically vascular malformations and hypervascular tumors (e.g. hemangioblastoma), selective spinal angiography represents an essential adjunct to MR. Selective angiography can also be used therapeutically to treat preoperatively or definitely vascular malformations (i.e. interventional neuroradiology). PMID- 1439685 TI - [Imaging of the spine]. AB - Modern imaging techniques allow early and precise diagnosis of spinal diseases. Their sensitivity and specificity are variable, but in general they are more complementary than competitive. After emphasizing the different patterns which characterize the late evolution of diagnostic imaging, the author reviews the indications and limits of plain films, bone scintigraphy, computed tomography, and in particular of magnetic resonance, in trauma, degenerative lesions, inflammations, infections and tumors of the spine. PMID- 1439686 TI - [Evaluation and documentation of tomographic images and further data using the Apple-Macintosh PC]. AB - Use of the personal microcomputer for the analysis of clinical cardial PET studies acquired at the Paul Scherrer Institute in Villigen, Switzerland. At present this is the only PET facility in Switzerland. As the local computers were not usually available for image analysis, it was necessary to find a convenient way to visualize and analyze the PET images in our department in the Cantonal Hospital, Aarau (distance to Villigen some 30 km). The personal microcomputer is, as other authors have already shown, in fact capable of handling the acquired images (128 by 128 pixels) easily. We use a Macintosh IIcx (16 MHz Motorola 68030 CPU) as image analysis workstation. In spring 1990 we implemented a software which could read the original Siemens matrix file directly into the Macintosh PC. As the handling of this software was somewhat clumsy, we now use a very powerful software ("Explorer", UCLA), which is specially designed for PET analysis. Analysis of PET data on the personal computer saves both time and money as we are able to use a standard PC periphery, which is less expensive than specially designed medical units. PMID- 1439687 TI - [Sphincter-preserving radiotherapy of anal carcinoma]. AB - During the last decade radiotherapy, in combination with chemotherapy, has become the treatment of choice in cure of anal carcinoma with preservation of anal function, and has replaced abdominoperineal resection (APR). From 1979-1990 54 patients with anal carcinoma were treated by radiotherapy. 24 patients received radiotherapy after APR (12 adjuvant, 12 after recurrence). 11 received palliative radiotherapy without prior APR. 19 patients were treated curatively, 17 of whom received a combination of external irradiation followed by interstitial iridium implantation in a split course regimen. 11 of the 19 patients received short simultaneous chemotherapy (mitomycin C and 5-fluorouracil). All 19 patients had a complete remission. 18/19 patients had no local recurrence after mean 14 months' follow-up. 2 patients developed regional recurrence. 3 patients died of other causes. Colostomy was necessary in 5/19 patients with anal necrosis which was dose-related. The maximum tolerated dose was 71.4 Gy. Our results support the recommendation in the literature of primary, curative, radiotherapy and chemotherapy of anal carcinoma with preservation of the anal sphincter. PMID- 1439688 TI - [Current aspects in the pathogenesis and therapy of glomerulonephritis: significance of glomerular metalloproteinases]. AB - The extracellular matrix, comprising the glomerular basement membrane and the mesangial matrix, plays a crucial role in glomerular structure and function. The glomerular extracellular matrix is composed of collagens, proteoglycans and glycoproteins. The distorted balance between synthesis and degradation of extracellular matrix proteins is a hallmark of many forms of glomerulonephritis, such as glomerulosclerosis. The degradation of the matrix occurs through the action of a group of extracellularly active metalloproteinases. Within the glomerulus these enzymes are synthesized by the epithelial and the mesangial cells. The molecular structure of the mesangial metalloproteinases, including their in vitro regulation, was analyzed and the in vivo synthesis of these proteinases was documented for cases of idiopathic rapid progressive glomerulonephritis and anti-Thy 1.1 nephritis. The therapeutic change in the activity and expression of the glomerular metalloproteinases, resulting in the restoration of physiologic matrix metabolic balance, opens up a new perspective for the therapy of glomerular inflammatory processes. PMID- 1439689 TI - [Immediate and long-term results of carotid endarterectomy: the Zurich experience]. AB - Extracardial carotid artery disease is a frequent cause of transient ischemic attack and of cerebral infarction. The records of 485 patients who underwent carotid endarterectomy between 1978 and 1991 were reviewed, with special attention to both cardiac and neurological complications. 432 patients had symptomatic carotid disease whereas 53 were asymptomatic but presented with significant carotid stenosis or a large ulceration at doppler-duplex examination and/or angiography. These examinations showed the following lesions in symptomatic patients: unilateral stenosis > 75% (331; 68.5%), ulceration (41; 8.5%), bilateral stenosis (61; 12.5%) and unilateral stenosis with contralateral occlusion (51; 10.5%). Intraluminal shunt was used in nearly all patients whereas special management of cerebral metabolism (intraoperative electroencephalogram, somatosensory evoked potentials) were used in high-risk patients only. Overall early mortality was 1.8%. Three patients died from the sequelae of a neurologic injury, whereas six patients died from myocardial infarction or intractable arrhythmia. Mortality decreased from 2.4% between 1978 and 1984 to 0.8% between 1985 and 1991. At 6 and 8 years, actuarial survival rates of 88.1% and 76.1% and stroke-free survival rates of 86% and 81.5% were observed. Late mortality was essentially due to ischemic cardiac complications (38.5% of the actuarial late mortality at 8 years). Review of the literature shows that carotid endarterectomy is the treatment of choice for symptomatic high-grade extracranial carotid stenosis in patients who are not high-risk candidates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439690 TI - [Reliability of bronchial tumor typing base on fibroscopically obtained biopsies]. AB - This study is based on the bronchial tumors biopsied and later examined between 1971 and 1986 at the Institute of Pathology, Lausanne. In each case the diagnosis based on the initial biopsy material is compared with the final surgical or autopsy diagnosis (Reference: Histological typing of lung tumours, second edition, WHO, 1981, 2). The series studied is constituted by 163 cases: 144 men (88.3%) and 19 women (11.7%). In 136 cases (83.4%), the biopsy diagnoses are identical to the diagnoses based upon surgical or autopsy material; in 27 cases (16.6%) these diagnoses differ. The positive predictive value of bronchial biopsy appears to be excellent (100%) for small cell and epidermoid carcinoma (CA). It is satisfactory for adenocarcinoma (85.7%) but insufficient for large cell CA (42.3%) and the tumors grouped under "others" (50%). The diagnosis of large cell CA, in situ CA, papillary tumor, undifferentiated CA, or carcinomatous lymphangitis should be considered with caution and in some cases it is advisable to repeat the biopsy. The discrepancies between the initial and final diagnoses can, in all cases, be attributed either to the biopsy specimen being too small and therefore nonrepresentative or, less frequently, to crushing and necrosis of the tissues. PMID- 1439691 TI - [Primary prevention of osteopenia]. AB - In industrialized countries the clinical and socioeconomic importance of osteoporosis has been well recognized in recent years. Various treatments have been introduced for secondary prevention in established osteoporosis. There is, however, a deficit in the primary prevention of osteopenia. In every age group physical exercise stimulates mineralization of the bone. With regular training adolescents can achieve a higher peak bone mass. In old age the physiologic decrease of bone mass can be retarded by physical exercise. A diet rich in calcium has positive effects on mineralization of the bone. Estrogens have proved efficacious in the prevention of osteoporosis in postmenopausal women. Abstinence from nicotine and alcohol contributes to the prevention of osteopenia. PMID- 1439692 TI - [Dental diagnosis is not to be replaced by the computer]. PMID- 1439693 TI - [The effect of 2 finishing methods on the micromorphology of the proximal box margin. An in-vivo study]. AB - Minipreparations of class II cavities often are not employed in daily practice mainly because adequate instruments for finishing the axial box margin and the proximo-cervical curvature were not available. The purpose of this in vivo study was to assess the morphology of the proximal box margin after finishing with two different methods. 81 class II minicavities for amalgam restorations were prepared by 4 dental practitioners. One method for finishing the axial box margin and the proximo-cervical curved border was the use of a modified EVA-System with the total amplitude reduced to 0.4 mm and a highly flexible file (Cavishape, grain 25 microns). The other method was the use of an axial margin trimmer. The micromorphology of the two methods was investigated by means of scanning electron microscopy and a score system as described earlier (Lussi et al. 1987). The margins of the axial box as well as of the proximo-cervical curvature were significantly better finished with the EVA-System and the highly flexible file compared to the axial margin trimmer (p < 0.001). The finishing time for the box margin was not significantly different using the EVA instrument or the axial margin trimmer. These findings confirm other in vitro investigations. This in vivo study shows that the modified EVA instrument with the highly flexible file (Cavishape, grain 25 microns) is clearly superior to the axial margin trimmer in finishing the box margin. This device allowed a significant better finishing of the axial box margin and the proximo-cervical curvature of minicavities in daily practice. PMID- 1439694 TI - [The preparation of enamel margin beveling in proximal cavities]. AB - Minicavities for posterior composite resin restorations were prepared in 24 caries-free teeth. The aim of this in vitro study was to evaluate the micromorphology of the proximal cavosurface bevel. The cavosurface bevel has been employed for many years as an accepted modification for composite restorations in permanent anterior teeth. The bevel provides more exposed enamel rod ends available for bonding. Using the acid-etch technique the resin-enamel bond is stronger with etched transverse sections of enamel prisms than with longitudinal sections. Enamel in the proximal and gingival wall of class II cavity preparations for restoration with composite should be beveled because prism direction is at right angles to the surface. The aim of this study was therefore to compare two methods for beveling the box margins of small proximal cavity preparations. One method for the preparation of the proximal bevel was the use of a modified EVA-System with the total amplitude reduced to 0.4 mm, the fixation of the file position and a new developed file (Bevelshape, grain 40 microns). The form of this file was modified in order to produce a short cavosurface bevel of the gingival and proximal wall without danger of damaging the adjacent tooth. The other method was the use of an axial margin trimmer. The micromorphology of the two methods was investigated by means of scanning electron microscopy and a score system as described earlier (Lussi et al. 1987). Statistical analysis revealed significant differences between the two groups. As compared to the axial margin trimmer the new device allowed a significant better finishing of the proximal bevel (p < or = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439695 TI - [The marginal sealing of composite inlays with different cavity liners]. AB - In this in-vitro study we investigated the sealing properties of composite inlays (EOS system) dependent on 8 different base materials. Using a dye-penetration test, the sealing was determined after mechanical and thermal cycling. A partially massive dye-penetration was detected in most cases when one of the following materials was used: a calciumsalicylate cement (Dycal), a combination of calciumsalicylate cement and a resin (Basic), a calcium hydroxide filled resin (Prisma VLC-Dycal), or a zinc phosphate cement (Harvard Cement). In contrast to this, we discovered a complete or almost complete sealing in most cases after application of chemically-cured glass ionomer cements (Ketac-Bond, Ketac-Bond Aplicap, Base-Line) or a light-cured glass ionomer cement (XR-Ionomer) as base materials. From these results it can be concluded that the choice of base materials has an influence on the marginal sealing of composite inlays after thermal and mechanical cycling. However, it is not possible to make a definitive statement on the suitability of these base materials under clinical conditions, because the results of dye-penetration tests have only limited clinical validity. PMID- 1439696 TI - [The surface roughness of orthodontic wires--a laser optical and profilometric study]. AB - The surface roughness of orthodontic wires is an essential factor that determines the effectiveness of arch guided tooth movement. Using the nondestructive technique of laser specular reflectance, the surface roughness of 11 nickel titanium orthodontic wires and a standard steel as well as a beta-titanium wire was measured. The results were compared with the results from surface profilometry. The smoothest wire, standard steel Hi-T, has an optical roughness of 0.10 microns, while the roughness from profilometry reached a value of 0.06 microns. The titanium molybdenum wire has an optical as well as a profilometric roughness of about 0.20 microns, while the roughness of the NiTi wires ranges from 0.10 microns to 1.30 microns. As the surface roughness not only influences the effectiveness of sliding mechanics, but also the corrosion behaviour and aesthetics, the manufacturers of orthodontic wires are asked to improve the surface quality of their products. PMID- 1439697 TI - [Implants in the edentulous mandible. Clinical experiences with the use of ITI implants in the edentulous mandible: a retrospective after 8 years. Internationales Team fur Implantologie]. PMID- 1439698 TI - [The distalization of molars by the mold-casting technic. The distalization of molars with the aid of the mold-casting technic--an alternative to headgear]. PMID- 1439699 TI - [Dental imaging. An image-processing computer system as a new diagnostic and communications resource for dentistry]. PMID- 1439700 TI - [The direct responsibility of the dentist]. PMID- 1439701 TI - [Dentistry in the Scandinavian states]. PMID- 1439702 TI - [Membrane technics in oral implantology]. PMID- 1439703 TI - [No obligatory HIV tests for hospital patients and medical personnel]. PMID- 1439704 TI - [Statistics on health insurance 1990]. PMID- 1439705 TI - [Signal transduction in normal and neoplastic cells]. AB - This review describes molecular mechanisms involved in intracellular signal transmission. Special focus is given on calcium and calcium binding proteins as signaling intermediates. These strictly controlled biochemical reactions prevent uncoordinated proliferation which may lead to tumor development. Generally, signal transduction pathways are very similar among higher eukaryotes. Mutations in genes responsible for signal transmission and growth control (protooncogenes and tumor suppressor genes) are often found in tumors or cancer cell lines. PMID- 1439706 TI - [Control of gastrointestinal strongylids in first year calves: use of Paratect Flex bolus at late pasture turnout]. AB - The efficacy of the Paratect Flex-Bolus for the control of parasitic gastroenteritis in calves was evaluated in a field experiment in the Swiss midland region. The bolus was administered to 9 first year grazing calves at 4 to 5 months of age before turnout on June 26 while 9 calves remained as untreated controls. Both groups were rotated between 8 paddocks that had been pregrazed by older cattle in spring. For a period of 12 weeks the faecal egg output of the treated calves was reduced significantly (p < 0.05) compared to the controls, whereas no significant differences were observed in the mean serum pepsinogen values of both groups. At the end of the experiment (November 14) the bolus treated calves showed a 4 kg weight gain advantage over the controls which was not significant. The mild infection levels in both groups were probably due to the low pasture contamination with infective larvae throughout the season which most likely resulted from the late turnout of the calves. An outbreak of dictyocaulosis was observed in both groups in October and confirmed that the Paratect Flex-Bolus provides insufficient protection against this infection. PMID- 1439707 TI - [Suspicion of visna in a sheep from Graubunden Canton]. AB - A lentivirus belonging to the group of retroviridae causes a chronic progressive interstitial pneumopathy (maedi) or a demyelinating encephalo-myelitis (visna) in sheep and goats. Pulmonary lesions of maedi as well as sero-positive, clinically healthy animals can be observed in Switzerland; visna, which even in countries with endemic infection does not occur frequently, is extremely rare. The head and cervical spine of an ewe with severe nervous troubles suspected of scrapie were submitted for postmortem examination. We found a demyelinating myelitis resembling visna. Immunocytochemical staining (PAP) to demonstrate the presence of the virus in paraffin sections was negative, but several animals of the flock proved to be seropositive for maedi/visna virus, which supports the histological diagnosis. Although there is no risk of an epidemic outbreak of maedi/visna in Switzerland, modes of transmission, eradication programmes and prophylactic measures successfully employed in countries with endemic maedi/visna are discussed. PMID- 1439708 TI - Using fetal tissue. PMID- 1439709 TI - The human voice. PMID- 1439710 TI - Meaning and mind in monkeys. PMID- 1439711 TI - Why do we age? PMID- 1439712 TI - Essential but expendable. When do master genes regulate cell growth? PMID- 1439713 TI - Shaking the tree. Will statistical analysis of DNA pinpoint human origins? PMID- 1439714 TI - Cellular response. Are antibodies the most effective defense against AIDS? PMID- 1439715 TI - [Intra-individual variation of cerebral blood flow velocity in sleeping and awake children]. AB - A considerable intraindividual variability of blood flow velocities in the middle and posterior cerebral artery was found in 74 children by continuous transcranial Doppler recording during EEG registration. The coefficient of variation of the mean flow velocities in the posterior cerebral artery was higher than in the middle cerebral artery, and higher in restless children than in calm children. During hyperventilation the mean flow velocities decreased to about 50 per cent of the baseline values. They increased to 130-140 per cent of the baseline values after hyperventilation. Repeated variations of the velocities of more than 30 per cent of the baseline values were observed during non-REM sleep in the majority of the children. They may be caused by a lower damping of the cerebral autoregulatory response. The intraindividual variability of cerebral blood flow velocities in children has to be kept in mind in pathological conditions and during Doppler monitoring. PMID- 1439716 TI - [Transcranial Doppler sonography with evaluation of CO2 reactivity in craniocerebral trauma]. AB - 17 patients with severe head injury were examined by transcranial Doppler sonography. Resting values and CO2 reactivity were determined. The resting measurements had no prognostic value. There was no significant side difference in patients with unilateral intracranial lesions. CO2 reactivity was 2.8 +/- 2.3%/mmHg pCO2 in patients with good outcome, whereas in patients with bad outcome CO2 reactivity was 0.6 +/- 5.1%/mmHg pCO2. However, in the acute situation after the trauma there was no difference between the two. In patients with a unilateral lesion we found a significantly lower CO2 reactivity on the side of the lesion of 1.8 +/- 0.4%/mmHg pCO2, on the non-affected side CO2 reactivity was 4.5 +/- 2.1%/mmHg pCO2. The conclusion is that the CO2 reactivity yields information on the actual haemodynamic situation in brain-injured patients. Repeated measurements are necessary to improve the prognostic value of CO2 reactivity, because this parameter may improve during treatment. PMID- 1439717 TI - [Various ultrasound methods for studying the vertebral artery--a comparative evaluation]. AB - In a prospective study 451 patients were examined with extracranial continuous wave (CW) Doppler sonography, transcranial Doppler sonography and color coded duplex sonography in order to evaluate the diagnostic accuracy of the three methods for vertebral artery pathology (hypoplasia, proximal and distal stenosis and occlusion). Color duplex sonography was used as the reference method. CW Doppler sonography (mastoidal slope) had a sensitivity of 100% and a specificity of 27% for the detection of pathological changes in vertebral arteries (VA). For suboccipital transcranial Doppler sonography these values were 38% and 58%. Extracranial Doppler sonography and transcranial Doppler sonography are often unsuitable for differentiating between proximal stenosis and hypoplasia of VA. Transcranial Doppler sonography of the terminal segments of VA resulted in normal flow parameters in 27% of cases with proximal stenosis and in 50% in cases of proximal occlusion. Flow was normal in these particular cases owing to a more distal collateralisation of the VA. The terms "hypoplasia" and "asymmetric" of VA are discussed. PMID- 1439718 TI - [Catheter-induced femoral artery lesions: diagnosis with B-mode ultrasound, Doppler ultrasound and color Doppler ultrasound]. AB - A total of 44 patients were evaluated to compare the value of B-mode sonography, Doppler sonography and colour coded Doppler sonography. All patients were studied because of suspected lesions of the femoral arteries following diagnostic and/or therapeutic cardiac catheterisation. B-mode sonography was unable to reliably differentiate between haematoma and pseudo-aneurysms, a.v.-fistula or combined lesions. Colour coded Doppler sonography can better demonstrate haematoma and thrombi in pseudo-aneurysms. The neck of a pseudoaneurysm can be exactly depicted by colour coded Doppler sonography. A.v.-fistula is shown by colour coded Doppler sonography based on typical colour coding and the Doppler spectrum. Combined lesions of pseudo-aneurysm and a.v.-fistula cannot reliably be detected by colour coded Doppler sonography, duplex sonography and B-mode sonography. PMID- 1439719 TI - Atlantoaxial instability in Down's syndrome: a case report and review. AB - Down's syndrome is the most common autosomal chromosomal abnormality in humans and is associated with a number of well known clinical findings. Atlantoaxial instability is a less recognized, yet potentially significant, manifestation of Down's that has gained importance because of the widespread participation of Down's syndrome individuals in athletic events. Early recognition and appropriate management of patients with atlantoaxial instability can significantly reduce the morbidity and mortality associated with this condition and guide patients and their parents toward continued safe participation in athletics. PMID- 1439720 TI - Tuberculous peritonitis: a case report and literature review. AB - We present a case of tuberculous peritonitis in the setting of alcoholic cirrhosis with ascites. A young American Indian male with alcoholic cirrhosis and ascites presented with low grade fever and weight loss. A diagnosis of tuberculous peritonitis was made by laparoscopic guided peritoneal biopsy. He was treated successfully with isoniazid and ethambutol for 24 months. The diagnosis of tuberculous peritonitis should be entertained in high risk populations such as American Indians, Asians, alcoholics, chronic ambulatory peritoneal dialysis patients and AIDS patients in the appropriate clinical setting. Definitive diagnosis can usually be made by laparoscopic guided peritoneal biopsy. PMID- 1439721 TI - Pediatric pain management. PMID- 1439722 TI - A condom sense approach to AIDS prevention: a historical perspective. AB - Condoms have come a long way since their use in ancient Egypt three millennia ago. Their benefit is well established for the prevention of both contraception and STDs. Although AIDS has revitalized the condom, we must remember that condoms do not prevent the spread of HIV infection, people do. Everyone must take personal responsibility to avoid high risk behavior (e.g.; IV drug use, promiscuous sex, casual sex, etc). If one does engage in high risk sexual behavior, he/she should at least use condom sense. PMID- 1439723 TI - Toxic metal pollution in Africa. AB - The available information suggests that the concentrations of toxic metals in many ecosystems of Africa are reaching unprecedented levels. Because of the heavy load of contaminated dusts in the air of the overcrowded cities, the ambient concentrations of toxic metals are now among the highest being reported anywhere. Lead pollution from the increasing number of automobiles and cottage industries represents a major health hazard, and it is estimated that 15-30% of the infants in some urban areas may already be suffering from lead poisoning. The cultural and lifestyle determinants of lead exposure and the greater susceptibility of African populations to environmental metal poisoning are highlighted. The suggestion is made that the environmental health criteria for toxic metals in the developed countries may not provide adequate protection for many African communities. PMID- 1439724 TI - The transport and fluvial redistribution of Chernobyl-derived radiocaeisum within the River Wye basin, UK. AB - Relatively little attention has been given to the long term prospect of fluvial transport processes redistributing Chernobyl-derived radiocaesium within the UK. Work undertaken within the Wye basin, central Wales, demonstrates a complex distribution of fallout at the catchment scale, with the bulk of the deposition concentrated in a narrow north-south band, situated in the west central areas of the basin, which contained in excess of 1500 Bq m(-2) of (134)Cs. Fluvial transport and redistribution of this material was demonstrated by river sampling during the winter of 1988/89, when the radiocaesium content of suspended sediment transported by the River Wye (approximately 30-50 mBq g(-1) of (137)Cs) remained 3-5 times higher than pre-Chernobyl levels. Floodplain reaches displayed variable levels of secondary contamination, dependent upon the upstream supply of radiocaesium and local morphological controls. Accordingly, the highest (134)Cs inventories within the basin (> 6000 Bq m(-2)) were associated with rapidly accreting floodplain sites. A number of these sites experienced only limited amounts of direct atmospheric fallout. The importance of fluvial redistribution as a secondary contamination mechanism is thus highlighted. PMID- 1439725 TI - Contamination of plants by resuspension: a review, with critique of measurement methods. AB - Resuspension of contaminated soil particles can be an important process that prolongs the availability of contaminants within the environment. Inhalation and inadvertent ingestion of resuspended soil particles may be important pathways to human exposure. Our understanding of the processes and mechanisms of resuspension onto plant surfaces are currently inadequate for accurate predictions. Part of this is due to the use of measurement techniques designed for inhalation studies that are not efficient for gaining understanding about phenomena occurring at the plant surface. I discuss the shortcomings of such techniques, review the data from a technique that currently has the most merit (mass loading), and suggest new techniques, as well as specific needs for future research. The paper's focus is on the contamination of plant surfaces by resuspended soil particles, not the inhalation of such particles. PMID- 1439726 TI - Solar UV irradiance and some biological consequences: Bombay, India. AB - Measurements of solar UV radiation (UVR) at Bombay, India, lattitude 18.5 North and longitude 72.5 East were recorded using Eppley UV radiometer for a 2-year period. The UV irradiance is calculated and presented. The annual and diurual trends in the quantitation of UVR are examined. The consequences of solar UVR and its projected increase are discussed with special reference to its biological effects and results of UVR on experimental animal systems vis a vis and epidemiological data in the Indian context. PMID- 1439727 TI - The transport of airborne trace elements copper, lead, cadmium, zinc and manganese from a city into rural areas. AB - The fluxes of the elements lead, zinc, copper, cadmium and manganese have been measured in the insoluble component of bulk deposition derived from Christchurch, New Zealand. Lead, zinc, copper and cadmium fluxes follow approximately exponential decay curves away from the city whereas manganese deposition showed little spatial variation. A similar composite source originating in the city is indicated for the lead zinc, copper and cadmium and a different major source occurs for manganese. In the city and nearby rural areas soil is not a major source of atmospheric lead, zinc, copper and cadmium, whereas at remote sites atmospheric levels of these elements are mostly soil derived. Seasonal variations in the bulk deposition are large within the city, and at upwind rural sites. The variations are controlled by meteorological conditions, in particular wind speed and the height of the mixing layer. Compared with overseas studies, the proportion of the metals occurring in the soluble fraction of the bulk deposition is low. This may be due to the relatively dry climate of the area. PMID- 1439728 TI - Occurrence of butyltin species in sewage and sludge in Canada. AB - Samples of sewage treatment influent, effluent and sludges collected monthly from five Canadian cities over the period from July 1990 to January 1991 were analysed for butyltin and octyltin species. Monobutyltin was found in all influent samples, but dibutyltin and tributyltin were found only infrequently, and octyltin species were not found at all. In the case of monobutyltin, there was significant reduction in its concentration by degradation and adsorption to sludge during passage through the sewage treatment plant. The average reduction was 40%. The monobutyltin found in the effluent likely came from its use as a poly (vinyl chloride) stabilizer, and from the degradation of tributyltin, which is used as a slimicide. No butyltin or octyltin species was found in five landfill leachate samples in southern Ontario during the same period. PMID- 1439729 TI - Radon concentrations inside castles and other ancient buildings. AB - Sixty-two measurements of Rn-222 concentrations were made in 24 castles and 13 ancient buildings in 30 different places situated in the provinces of Parma and Reggio Emilia (Northern Italy). The method used was that of activated carbon canisters which were placed in selected settings for at least 48 h in the period starting from December 1990 to May 1991. It was possible to determine the amount of radon in each canister via its daughters gamma emitters counted by NaI(T1) and Ge(I) detectors. The mean radon concentrations were 72 Bq m-3 (arithmetic mean) and 49 Bq m-3 (geometric mean), a good deal higher than the values obtained from measurements carried out in modern dwellings in the same area; 30 Bq m-3 (arithmetic mean) and 19 Bq m-3 (geometric mean). PMID- 1439730 TI - In vivo detection of genotoxicity in waste water from a wheat and rye straw paper pulp factory. AB - The genotoxicity of waste water from a wheat and rye straw paper pulp mill was investigated by in vivo genotoxicity tests using micronuclei and sister chromatid exchange as endpoints. Micronuclei were studied in mussels (Mytilus edulis) and sister chromatid exchange in fish (Nothobranchius rachowi). The paper mill uses chlorine dioxide for bleaching, and the bleaching effluent as well as the combined effluent, i.e. the mixture of all waste water streams, were both tested. Both effluents induced micronuclei and sister chromatid exchanges, although the presence of toxic substances could mask the expression of genotoxicity in some cases for both test systems. The study revealed that genotoxins are produced in the chlorine dioxide bleaching process as well as in the pulping process, indicating also genotoxic activity of non-chlorinated compounds. In contrast to previous studies in which mutagenicity was determined with bacterial assays, genotoxins were only associated with chlorinated organics from bleaching with chlorine and failed in detecting genotoxins in chlorine dioxide bleaching effluents. Aquatic in vivo genotoxicity tests are sensitive and efficient systems and seem to be a promising tool in effluent testing. PMID- 1439731 TI - ELISA test, a new method to detect and quantify isoproturon in soil. AB - An indirect competitive Enzyme-Linked ImmunoSorbent Assay (ELISA) has been developed to quantify isoproturon (a commonly used phenylurea herbicide) in soil samples. To produce the specific antibodies needed for detection of isoproturon, an isopropylanilin analogue was covalently linked to a proteic carrier and the resulting conjugate used as immunogen. Hybridomas were obtained from spleen cells of mice immunized with this conjugate. One specific monoclonal antibody (MAb) was selected and used to the ELISA allowing the detection of small amounts of herbicide (20-250 micrograms l-1). Cross-reactivities with other current phenylureas appear to be insignificant. Samples of six soils were mixed with several quantities of herbicide (to reach final concentrations ranging between 0.15 and 1 microgram g-1) and extracted either with methanol to determine the total residue or with a solution of CaCl2, to establish the herbicide available from the soil solution. The extracts were analyzed simultaneously by gas chromatography and ELISA in these conditions, correlation coefficients between both methods were never lower than 93.5%. Organic matter and ionic strength appeared to be the most important parameters interfering the ELISA test. To avoid these drawbacks, standard curves were established for the ELISA by spiking isoproturonless soils extracts. In these conditions, correlations between both methods were considered as sufficient. ELISA of untreated samples were carried out to verify the isoproturon availability curves established previously. PMID- 1439732 TI - Biological and chemical interactions of pesticides with soil organic matter. AB - There is little doubt that organic matter plays a major role in the binding of pesticides in soil, and that this phenomenon is usually the most important cause for interaction of pesticides in the soil environment. Fulvic or humic acids are the chemicals most commonly involved in the binding interactions. Binding can occur with the original pesticide or a transformation product, the reaction being caused by abiotic agents or biotic agents (microbial or plant enzymes). The reactions or processes involved appear to be the same as those responsible for the formation of humic substances, i.e. for the humification process. Binding of pesticides to organic matter can occur by sorption (Van der Waal's forces, hydrogen bonding, hydrophobic bonding), electrostatic interactions (charge transfer, ion exchange or ligand exchange), covalent bonding or combinations of these reactions. Our investigation focused primarily on the binding of substituted phenols and aromatic amines to humus monomers and humic substances. In model reactions, we demonstrated the formation of covalent linkages between pesticides and humus constituents and fulvic or humic acids in the presence of phenol oxidases or clay minerals. With chlorinated phenols and carboxylic acids, it was possible to isolate and identify cross-coupling products and to elucidate the site and type of binding. The binding of chlorinated phenols to humic substances was determined by using 14C-labelled chemicals and by measuring the uptake of radioactivity by the humic material. These experiments provide a base for explaining the formation of bound residues in certain cases and for assuming the toxic potential of the immobilized pollutants. PMID- 1439733 TI - Molinate decontamination processes in effluent water from rice fields. AB - The performance of aeration, photodecomposition and biological degradation processes as methods to reduce molinate contamination levels in effluent water from rice fields was studied. Aeration produced a molinate dissipation of 84%, as against 22% without aeration. Application of UV-light to clean water solutions achieved a molinate photodecomposition of 96% in 24 h. Maximal degradation obtained in algal cultures was 55% in 20 days and 78% in 40 days. In micro organism cultures, kept in darkness and with a continuous flow of aqueous solution of molinate and inorganic salts, a degradation of 97% was achieved. PMID- 1439735 TI - Gas chromatographic determination of some modern pesticides in fruits. AB - A method was developed for determination for residual amounts of some modern insecticides, acaricides and fungicides in fruits. The pesticides were extracted with methanol and partitioned into chloroform. The extract was purified by column chromatography on sodium sulphate/Florisil/Celite/charcoal. Analysis by gas liquid chromatography with 63Ni electron capture detection was completed successively on a column (150 cm x 4 mm) with 3% SE-30 and a column (150 cm x 2 mm with 3% OV-17 liquid phase. Recoveries of 17 pesticides from fortified samples of apples ranged from 83.3% to 98.4% for a level of 0.1 mg/kg. PMID- 1439734 TI - Degradation of aliphatic halogen-substituted pesticides by dehalogenase isolated from Pseudomonas alcaligenes. Identification and properties of the enzyme. AB - Some characteristics of a 2,2-dichloropropionate dehalogenase induced in a bacterial strain capable of degrading high concentrations of the herbicide dalapon were studied. Polyacrilamide gel electrophoresis of the crude cell free extracts identified only one type of dehalogenase. The single enzymatic protein showed activity against a variety of chlorinated aliphatic acids but differed in their activity levels. Thus activity in mumol substrate converted (mg protein)-1 min-1 was 2-monochloropropionate 0.65, 2,2-dichloropropionate 0.56, 2 monochloroacetate 1.70 and 2,2-dichloroacetate 1.00. In the crude extracts, the enzyme activity against 2,2-dichloropropionate was optimal at a broad pH range with a mid-point at pH 9.5 and apparent Km values were within the range 0.23-0.73 mM. PMID- 1439736 TI - Relationship between the biodegradative capability of soil micromycetes for pentachlorophenol and for pentachloronitrobenzene. AB - A collection of 1056 strains in our laboratory were incubated with various xenobiotics among which were two potent fungicides: pentachlorophenol (PCP) and pentachloronitrobenzene (PCNB). The production of extracellular phenoloxidases were examined, using a series of ten different reagents. On the whole, PCNB is less accessible to fungal degradation than PCP. Although no correlation was found between the biodegradative capability of individual fungal strains for PCP or for PCNB, when taxonomic groups were considered as a whole, the same activity profiles were found. Zygomycetes were the most efficient; yeasts the least efficient towards both substrates. A more detailed study of the metabolism of both substrates on selected strains is in progress. PMID- 1439737 TI - Evidence of reduced poly-B-hydroxybutyrate biosynthesis in free-living nitrogen fixing bacteria, Azotobacter chroococcum, following acquired resistance to the fungicide captan. AB - Some biological activities of Azotobacter chroococcum, strain Azcap 1, (spontaneous mutant, captan resistant up to 300 micrograms/ml) were assayed on RM medium with and without the presence of the fungicide. Comparisons were also carried out with Az. chroococcum sensitive strains Azwt, Azcan 10 and 14. The hydrolysis of captan, incorporated in agar plates of RM at 100 micrograms/ml, was rapid, since on 4-day plates, no effect was found on the strain Azwt, while on freshly prepared ones its growth was completely blocked. As for Azcap 1, grown on RM only, the behaviour was similar to that of sensitive strains, whereas when grown on captan the results of experiments showed: (i) a lag of approximately 12 h to reach the maximum nitrogen-fixing activity; (ii) delay of 12-24 h in the full consumption of glucose present in the medium, although the invertase activity did not present differences; (iii) high ATP culture content during the 50 h of the experiment; (iv) approximately 6-10-fold lower production of PHB (poly-B-hydroxybutyrate); (v) lack of typical encystment phase, for the tested 96 h and reduced viability in developing colonies on agar RM medium. In contrast, when captan was added to cultural medium at sublethal concentration, 50 micrograms/ml for sensitive strain Azwt and 200 micrograms/ml for Azcap 1, the amount of glutathione produced (to remove the fungicide toxicity) was several times higher for the former. PMID- 1439738 TI - High-performance liquid chromatographic determination of the herbicide imazapyr residues in water and soil. AB - A rapid method for determining residues of the herbicide imazapyr in water and soil is described. The soil samples were extracted with aqueous methanol and, after concentrating, the residue was estimated by HPLC with UV detection at 250 nm. Imazapyr dissolved in water was quantified by injecting the samples without any previous treatments. Analyses were performed without clean-up of soil and water samples. The pre-concentration of samples was required only at very low herbicide amounts. The maximum recovery was achieved by methanol/water (3:2 v/v) with both soils after three extraction procedures. The detection limits were 0.01 mg/l and 0.05 mg/kg in water and soil, respectively. PMID- 1439739 TI - Mobility of dichlorprop in the soil-water system as a function of different environmental factors. I. A batch experiment. AB - Batch experiments were conducted to study the mobility of 14C-labelled dichlorprop in different soil types. Soils rich in organic carbon showed high sorption capacity compared to sand soil with low content of organic C. Soil to soil variations decreased when corrected for different content of organic C (Kd normalized to Koc). Data obtained in batch experiments fit into linear as well as Freundlich sorption isotherms (17 degrees C). Desorption of [14C]dichlorprop in the soil-water system increased with pH. A significant amount of dichlorprop may be considered as 'non-available' in soils with high organic C, even at relatively high pH-values. The octanol/water partitioning coefficient (Kow) for dichlorprop was inversely related to pH. In the pH range 4-7, the Kow-value varied from 114 to 0.6. The relationship between Koc and pH was similar to the relationship between Kow and pH and the data fitted the following equation: log Koc = 0.5 log Kow + 0.2 (r2 = 0.986). PMID- 1439740 TI - Mobility of dichlorprop in the soil-water system as a function of different environmental factors. II. A lysimeter experiment. AB - Lysimeter experiments were conducted to study the leaching of [14C]dichlorprop and [3H]water through different soil columns. Results from soil columns collected at Haslemoen showed that an upper silt loam layer (0-18 cm) had higher retention capacity than the underlying sandy loam (35-60 cm) and fine sand (70-95 cm) layers. Leaching through silt clay loam (0-18 cm) columns from Ullensaker was very fast. When the columns received an amount of water corresponding to approximately 10 mm precipitation, up to 50% of the added [14C]dichlorprop leached through the columns. This is probably due to rapid downward movements through macropores (e.g. cracks). PMID- 1439741 TI - Analytical methodology for screening organophosphorus pesticides in biota samples. AB - The use of gel permeation chromatography (GPC) and capillary gas chromatography (GC) with thermionic detection (NPD) is described as a routine methodology for the determination of organophosphorus pesticides in biota samples. Confirmatory analysis is done by capillary GC with mass spectrometry in the negative chemical ionization mode (NCI-MS). As an example, the use of GPC is described as trace enrichment technique and clean-up to remove coextractive lipids in samples of mosquito fish Gambussia affinis collected during periods of 1987-1989 in the rice crop fields of the Ebro Delta (Spain). Recoveries of dioxathion, fenitrothion, malathion, tetrachlorvinphos, azinphos-ethyl, ronnel and coumaphos varied between 60% and 80% depending on the compound. PMID- 1439742 TI - Assessment of the movement of triazole fungicides by soil thin-layer chromatography. AB - Soil TLC was used to assess and compare the mobility of 17 triazole fungicides in soil. A sample of Versailles soil (a silt loam with 2% organic matter) was passed through a 100-microns-meshed screen, and glass plates were coated with this fine fraction at a thickness of 250 microns or 500 microns. The non-labelled compounds were bioassayed to visualize their movement. Penicillium expansum was used as visualizing agent by spraying plates with an agar suspension of the fungus. Plates were then incubated at 28 degrees C, 100% RH. Inhibition areas usually appeared within 36 h. When [14C]triazoles were available, a linear detector and autoradiography were used to visualize the movement and measure the Rf. The Rf values obtained indicate that most of the fungicides were slightly mobile in the Versailles soil. Mobility of these fungicides was inversely related to their octanol/water partition coefficient. Successive leaching were also carried out with radiolabelled compounds, and movement was measured with the linear detector and compared with the position predicted from the initial value of Rf. The advantages and drawbacks of this technique are discussed. PMID- 1439743 TI - Criteria for evaluating the impact of pesticides on groundwater quality. AB - A lot of data and information are available regarding the presence of pesticides in ground-waters or their tendency to contaminate them. Despite this, for a very large number of pesticides these data and information are almost completely lacking. Many theoretical methods have been proposed to predict the leaching potential of pesticides. Persistence (expressed by DT50) and mobility (expressed by Koc) are key parameters that seem to be particularly representative of the overall leaching potential of nonionic compounds and they are widely used in these methods. Nevertheless, these parameters may vary greatly causing sharp differences in ranking the leaching potential of pesticides. Indeed, when the GUS Index is calculated using the available published values of Koc and DT50 in combinations representing the minimum, medium and maximum leaching potential of herbicides, very different results can be obtained. Many of these compounds can be classified as contaminants or non contaminants, depending on the type of combination used. PMID- 1439744 TI - Mathematical descriptions of accelerated transformation of 1,3-dichloropropene in soil; a microbiological assessment. AB - The rate of transformation of the soil fumigant (Z)-and (E)-1,3-dichloropropene in moist soil layers was measured at incubation temperatures of 5 degrees C, 10 degrees C and 20 degrees C. 'DD95' was added to four characterized soil layers, in amounts corresponding to realistic field contents after fumigation. Rapid transformation immediately after application was observed in layers with low initial contents (30-300 micrograms/kg dm) and could well be described with a first-order rate model. Incubation at higher doses (5-15 mg/kg dm respectively) showed distinctly different transformation pathways. Degradation curves could well be computed using a microbiological interspective competition (MIC) model for moist soil. The transformation rate is inversely correlated to microorganism population size and growth. Transformation curves described by MIC are characterized by a lag-time, a period of accelerated transformation and a period of decreasing transformation rates. At low temperatures, DT50 values of more than 20 days could be observed. First-order rate computations did not exceed 8 days. The use of different mathematical discriptions for various soil layers and soil temperatures permits simulation of DD95-transformation by microorganisms in the soil profile throughout the growing season. PMID- 1439745 TI - Binding mechanisms of pesticides to soil humic substances. AB - This review-paper summarizes and discusses the nature of the binding forces involved and the types of mechanisms operating, often simultaneously, in the adsorption processes of several pesticides onto soil humic substances, humic acids and fulvic acids. These include ionic, hydrogen and covalent bonding, charge-transfer or electron donor-acceptor mechanisms, Van der Waals forces, ligand exchange, and hydrophobic bonding or partitioning. Experimental evidence obtained and interpretation provided for the various adsorption processes proposed are briefly presented and commented. The review ends with some concluding remarks and recommendations for future work needed to be done. PMID- 1439746 TI - Determination of trace element speciation and the role of speciation in aquatic toxicity. AB - Knowledge of trace element speciation in waters is essential to an understanding of aquatic toxicity and bioaccumulation, as well as to the partitioning of elements between water and colloidal and particulate phases. In natural waters, only very small percentages of the dissolved heavy metals, such as copper, lead cadmium or zinc, are present as free (aquo) metal ion; most of the metal is adsorbed to colloidal particles or combined in complexes. For aquatic toxicity studies, the aim of the speciation measurement is to determine the fraction of total dissolved metal (the 'toxic fraction') that will react with, and be transported across, a biological membrane such as a fish gill. In this review, a range of trace element speciation techniques is discussed and compared. A simple anodic stripping voltammetric method is recommended for the measurement of the fraction of electroactive metal in a sample, i.e. the fraction of total dissolved metal that can be deposited into a mercury electrode at the natural pH of the sample. The electroactive fraction is believed to approximate the toxic fraction. A rapid ion exchange method, suitable for field use, is proposed for the determination of the toxic fraction of copper in waters. PMID- 1439747 TI - Comparison of wet digestion procedures for the determination of cadmium and lead in marine biological tissues by Zeeman graphite furnace atomic absorption spectrophotometry. AB - Three wet digestion procedures, namely, nitric acid/sulphuric acid, nitric acid/hydrogen peroxide and nitric acid/perchloric acid were compared for their relative efficiency in determining cadmium and lead in marine biological tissues. The nitric acid/perchloric acid procedure was the most efficient, whereas the nitric acid/hydrogen peroxide procedure was the least efficient. The nitric acid/sulphuric acid procedure was also found to be effective but there was a problem with the method as the presence of sulphuric acid in the matrix markedly suppressed the absorbance signals especially for lead analysis and thus reduced sensitivity. The addition of ascorbic acid as matrix modifier improved sensitivity. However, this analysis still required the standard addition method. No apparent interferences were encountered for cadmium analysis. PMID- 1439748 TI - The use of an oxygen bomb as an alternative method for digestion of fish tissue for total mercury analysis. AB - One of the major time consuming steps in many of the methods used for the analysis of fish tissue for total mercury is the wet oxidation by concentrated acids. This paper compares the use of an oxygen bomb with the nitric/sulfuric acid wet oxidation technique for the determination of total mercury in fish tissue. No significant differences existed in the concentrations obtained by wet oxidation and bomb oxidation with absorption by deionised distilled water. When only a small number of samples (< 5) is to be analysed the oxidation bomb is quicker than published techniques. The oxygen bomb technique lacks the hazardous problems associated with the use of concentrated acids and produces a digest suitable for the determination of other elements but has a requirement for added capital cost. PMID- 1439749 TI - The social epidemiology of disease with particular emphasis on multiple sclerosis. AB - A particular conceptual perspective in the epidemiology of disease is discussed and evaluated: (1) that epidemiologic research is concerned with investigating the possible role played by biological and environmental factors in the etiology of disease but that the particular approach of the social epidemiologist is to concentrate on sociodemographic factors in the explanation; and (2) that a rich tradition of conceptual linkage already exists in epidemiologic research whereby sociologists working separately or in concert with epidemiologists, or physician epidemiologists concerned with details of social behavior and group relationships, have collected an analyzed sociodemographic data on the etiology of all kinds of disease conditions, inclusive of multiple sclerosis (MS). This paper is divided into four subsections which give an indication of its focus: (1) epidemiology and social epidemiologic research; (2) sociodemographic factors in epidemiologic research; (3) contribution of sociology to the social epidemiology of disease; and (4) sociodemographic factors in epidemiologic research on MS. This latter subsection includes a review and critique of some of the most frequently investigated sociodemographic factors in MS research: age, sex, race and socioeconomic status. Although the etiology of MS remains a mystery, sufficient epidemiologic evidence exists to connect three of these four sociodemographic factors to the etiology and distribution of this disease. PMID- 1439750 TI - Polycyclic aromatic hydrocarbons in air samples of meat smokehouses. AB - In a screening programme nine Danish meat smokehouses were randomly selected for measurements on concentration of airborne polycyclic aromatic hydrocarbons (PAH). A total of 23 stationary air samples were collected during the entire working period of the kiln either above the kiln doors or approximately 2 m in front of the kiln doors (i.e. total exposure on the day of sampling). Three of these samples had a PAH content below the detection limit of the highly sensitive assay employed. Furthermore, eight personal air samples were collected during the periods of tending the kiln (i.e. peak exposure measurement). Three of these samples were below the detection limit. Total airborne PAH concentration of the stationary air samples calculated as the sum of the concentration of 16 selected PAH compounds, was in general far lower than the total airborne PAH concentration measured in the same manner in smokehouses curing fish (Nordholm et al., 1986). In contrast to the study on PAH exposure in smokehouses curing fish, the present study revealed no significant difference between total PAH content in air samples collected above the kilns compared with samples collected approximately 2 m in front of the kiln doors. Calculation of the relative content of the individual PAH compounds in the stationary air samples collected in meat smokehouses showed naphthalene to be the major compound in (70% +/- 26% of total PAH), whereas the relative content of carcinogenic PAH compounds in average represented 4.0% of the total PAH content. However, only approximately 15% of the stationary air samples with detectable content of total PAH contained detectable amounts of carcinogenic PAH compounds. Hence it was concluded that PAH exposure during cold meat curing might be considered a limited health hazard compared with PAH exposure during hot fish curing. PMID- 1439751 TI - Concentrations of copper, zinc and lead in the Sydney rock oyster, Saccostrea commercialis (Iredale and Roughley) from the Georges River, New South Wales. AB - Copper, zinc and lead were analysed from samples of non-commercially grown Sydney rock oysters collected from the Georges River estuary in spring 1987. The results, when compared with previous data from 1975, indicated a marked increase in the concentration of copper (up to 40%) and zinc (up to 300%). For several sites, the recommended (National Health and Medical Research Council) levels for copper and zinc (70 micrograms g-1 and 1000 micrograms g-1 respectively) were exceeded. There appears to be a decrease in the concentration of lead since 1975. The gradient of increasing copper and zinc concentrations with increasing distance upstream from the mouth of the estuary reported in 1975 could not be statistically validated. A significant correlation was found between copper and zinc loadings in the oysters. It was noted that data collected in 1975 were based on commercially grown oysters. The use of commercially grown oysters, rather than indigenous oysters, to examine interaction of contaminant load and distance upstream, is complicated as commercial oysters are moved within the estuary and between estuaries to maximise growth potential. PMID- 1439752 TI - Fish as a source of exposure to mercury and selenium. AB - In a total of 395 subjects with varying fish consumption habits, mercury levels in whole blood (B-Hg), and selenium levels in plasma (P-Se) were studied. Also, in subcohorts, mercury levels in blood cells (Ery-Hg; n = 79), plasma (P-Hg; n = 158) and urine (U-Hg; n = 125) were analysed. There were statistically significant associations between fish intake on the one hand, and B-Hg, Ery-Hg and P-Hg, on the other, but not so with U-Hg. In subjects who never had fish, the average B-Hg was 1.8 ng/g, in subjects who had at least two fish meals each week, 6.7 ng/g. Ery-Hg, and to a less extent P-Hg, were associated with levels of marine n-3 polyunsaturated fatty acids (PUFA) in serum phosphatidylcholine. P-Hg and U-Hg were associated with numbers of teeth with amalgam fillings. P-Se also correlated with fish intake. In subjects who never had fish, P-Se averaged 80 micrograms/l, in subjects who had at least two fish meals per week, 91 micrograms/l. There was an association between PUFA and P-Se. Further, there were statistically significant associations between P-Se on the one hand, and B-Hg, Ery-Hg and P-Hg on the other. The data clearly demonstrate the importance of fish for the exposure to methylmercury and selenium in the Swedish diet, and the impact of amalgam as a source of exposure to inorganic mercury. PMID- 1439753 TI - A source inventory and budget for chlorinated dioxins and furans in the United Kingdom environment. AB - Polychlorinated dibenzo-p-dioxins (PCDDs) and -furans (PCDFs) are ubiquitous in the environment. This paper estimates the present UK environmental loading of PCDD/Fs in soils, vegetation, air, water and sediments. Greater than 95% of the estimated total PCDD/F loading of 5.7 t in the UK environment is present in surface soils. Annual emissions from known primary sources of PCDDs and PCDFs are estimated. The most important of these include: municipal waste incinerator stack emissions (10.9 kg sigma PCDD/F per annum); industrial (7.7 kg/year) and domestic (5.1 kg/year) combustion of coal; clinical waste incinerators (1.7 kg/year); volatilisation from chlorophenol-treated substrates (1.7 kg/year) and combustion of leaded petrol by motor vehicles (0.7 kg/year). These sources are generally easy to define and reasonably reliable national estimates can be obtained. More difficult to quantify are secondary releases from the large UK stock of pentachlorophenol (PCP) and PCP-treated products, which may represent quantitatively one of the most important sources of total PCDD/Fs to the environment. Estimates of homologue-specific emissions indicate that combustion processes represent a far more significant source of tetra and penta CDD/Fs than do chlorophenols, which in turn constitute a greater source of hepta- and octachlorinated congeners. Direct emission of PCDD/Fs into the atmosphere from combustion processes facilitates their atmospheric transport to remote locations. This, coupled with the diffuse nature of combustion processes, means that the effects of PCDD/F contamination originating from anthropogenic combustion are more widespread than those from the use and disposal of chlorophenols. Contamination from chlorophenols will be more localised, owing to the insignificance of direct atmospheric release pathways for this source. Although there is reasonable agreement between the estimated current annual flux and the present UK environmental loading of PCDDs and PCDFs, a large discrepancy exists between the sum of the annual contributions from primary sources and this annual flux. Whilst the existence of an as yet unidentified source or sources or gross underestimates of known sources cannot be excluded, it is proposed that much of this discrepancy may be accounted for by secondary releases from the use and disposal of chlorophenols and the long-range transport, continued remobilisation and subsequent redeposition of PCDDs and PCDFs already present in the environment. Despite limited evidence for a modest decline in levels of PCDDs and PCDFs in some environmental compartments over the last 20 years, the environmental persistence of these chemicals means that they will remain in the UK environment for the foreseeable future despite recent action to curb primary emissions. PMID- 1439754 TI - Atmospheric deposition of trace elements around point sources and human health risk assessment. I: Impact zones near a source of lead emissions. AB - The deposition of lead was monitored over 8 years in the area around a car battery factory north of Copenhagen, Denmark. The area also has heavy traffic. Deposition was measured by in-situ grown vegetables, transplant grass culture biomonitors, bulk deposition and soil samples. Three impact zones were identified by a multivariate statistical analysis. Within each zone, the total dietary intake of lead was estimated for adults and children as a percentage of the provisional tolerably weekly intake (PTWI), and as a result recommendation on restrictions in use of locally grown fruit and vegetables were given to the public. The pattern of lead deposition in the area during the period 1981-1988 was monitored and the amount of lead ingested via vegetables was toxically evaluated. Lead emission reduction measures introduced in the factory and in the traffic during the period produced significant reductions in lead deposition. PMID- 1439755 TI - Atmospheric deposition of trace elements around point sources and human health risk assessment. II. Uptake of arsenic and chromium by vegetables grown near a wood preservation factory. AB - Kale, lettuce, carrots and potatoes were grown in 20 experimental plots surrounding a wood preservation factory, to investigate the amount and pathways for plant uptake of arsenic and chromium. Arsenate used in the wood preservation process is converted to the more toxic arsenite by incineration of waste wood and is emitted into the atmosphere. Elevated concentrations of inorganic arsenic and chromium were found both in the test plants and in the soil around the factory. Multivariate statistical analysis of the results indicated that the dominating pathway of arsenic and chromium from the factory to the leafy vegetables grown nearby was by direct atmospheric deposition, while arsenic in the root crops originated from both the soil and the atmosphere. Consumption of vegetables grown near the source would result in an increased intake of inorganic arsenic, but the intake via the total diet was estimated to be below the provisional tolerable daily intake for inorganic arsenic established by FAO/WHO. PMID- 1439756 TI - Genome analysis and the human X chromosome. AB - A unified genetic, physical, and functional map of the human X chromosome is being built through a concerted, international effort. About 40 percent of the 160 million base pairs of the X chromosome DNA have been cloned in overlapping, ordered contigs derived from yeast artificial chromosomes. This rapid progress toward a physical map is accelerating the identification of inherited disease genes, 26 of which are already cloned and more than 50 others regionally localized by linkage analysis. This article summarizes the mapping strategies now used and the impact of genome research on the understanding of X chromosome inactivation and X-linked diseases. PMID- 1439757 TI - Genome delight. PMID- 1439758 TI - Immuno-PCR: very sensitive antigen detection by means of specific antibody-DNA conjugates. AB - An antigen detection system, termed immuno-polymerase chain reaction (immuno PCR), was developed in which a specific DNA molecule is used as the marker. A streptavidin-protein A chimera that possesses tight and specific binding affinity both for biotin and immunoglobulin G was used to attach a biotinylated DNA specifically to antigen-monoclonal antibody complexes that had been immobilized on microtiter plate wells. Then, a segment of the attached DNA was amplified by PCR. Analysis of the PCR products by agarose gel electrophoresis after staining with ethidium bromide allowed as few as 580 antigen molecules (9.6 x 10(-22) moles) to be readily and reproducibly detected. Direct comparison with enzyme linked immunosorbent assay with the use of a chimera-alkaline phosphatase conjugate demonstrates that enhancement (approximately x 10(5)) in detection sensitivity was obtained with the use of immuno-PCR. Given the enormous amplification capability and specificity of PCR, this immuno-PCR technology has a sensitivity greater than any existing antigen detection system and, in principle, could be applied to the detection of single antigen molecules. PMID- 1439759 TI - The B cell antigen receptor complex: association of Ig-alpha and Ig-beta with distinct cytoplasmic effectors. AB - The B cell antigen receptor complex is a hetero-oligomeric structure composed of antigen binding, membrane immunoglobulin, and transducer-transporter substructures. The transducer-transporter substructure is composed of disulfide linked dimers of immunoglobulin (Ig)-alpha and Ig-beta/gamma subunits that are products of the mb-1(alpha) and B29 (beta/gamma) genes. Although the receptor complex associates with Src family kinases that are activated after receptor ligation, the site of interaction of these and other cytoplasmic effector molecules with receptor subunits is unknown. The cytoplasmic tails of Ig-alpha and Ig-beta chains were found to associate with distinct sets of effector molecules. The Ig-alpha chain cytoplasmic domain bound to the Src family kinases Lyn and Fyn, phosphatidylinositol-3 kinase (PI-3 kinase), and an unidentified 38 kilodalton phosphoprotein; the cytoplasmic tail of Ig-beta bound PI-3 kinase and unidentified 40- and 42-kilodalton phosphoproteins. Binding activity was found to occur within a 26-amino acid sequence of Ig-alpha and Ig-beta that contains a motif [(Asp or Glu)-(any amino acid)7-(Asp or Glu)-Tyr-(any amino acid)3-Leu-(any amino acid)7-Tyr-(any amino acid)2-(Leu or Ile)] previously implicated in signal transduction via other receptors including the Fc epsilon receptor I and the T cell antigen receptor. These findings indicate that the subunits act independently to activate distinct second messenger pathways. PMID- 1439760 TI - Production of the Alzheimer amyloid beta protein by normal proteolytic processing. AB - The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (beta AP), which is deposited as amyloid in the brains of patients with Alzheimer's diseases, is derived from a large protein, the amyloid beta protein precursor (beta APP). Human mononuclear leukemic (K562) cells expressing a beta AP-bearing, carboxyl terminal beta APP derivative released significant amounts of a soluble 4 kilodalton beta APP derivative essentially identical to the beta AP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length beta APP and M17 cells expressing only endogenous beta APP also released soluble 4-kilodalton beta AP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton beta AP that is essentially identical to the 4 kilodalton beta AP deposited as insoluble amyloid fibrils in Alzheimer's disease. PMID- 1439761 TI - Structural basis of the intrasteric regulation of myosin light chain kinases. AB - The smooth muscle myosin light chain kinase (smMLCK) catalytic core was modeled by using the crystallographic coordinates of the cyclic AMP-dependent protein kinase catalytic subunit (cAPK) and a bound pseudosubstrate inhibitor peptide, PKI(5-24). Despite only 30% identity in amino acid sequence, the MLCK sequence can be readily accommodated in this structure. With the exception of the short B helix, all major elements of secondary structure in the core are very likely conserved. The active site of the modeled MLCK complements the known requirements for peptide substrate recognition. MLCK contains a pseudosubstrate sequence that overlaps the calmodulin binding domain and has been proposed to act as an intrasteric inhibitor and occupy the substrate binding site in the absence of Ca(2+)-calmodulin. The pseudosubstrate sequence can be modeled easily into the entire backbone of PKI(5-24). The results demonstrate that the intrasteric model for regulation of MLCK by intramolecular competitive inhibition is structurally plausible. PMID- 1439762 TI - An uncertain start for a brain decade. PMID- 1439763 TI - Two chromosomes down, 22 to go. PMID- 1439764 TI - Can a father's exposure lead to illness in his children? PMID- 1439765 TI - Dodging the needle in health care. PMID- 1439766 TI - Testing to begin on malaria vaccine. PMID- 1439767 TI - Hidden messages in genetic maps. PMID- 1439768 TI - Calmodulin and myosin light chain kinase: how helices are bent. PMID- 1439769 TI - The human Y chromosome: a 43-interval map based on naturally occurring deletions. AB - A deletion map of the human Y chromosome was constructed by testing 96 individuals with partial Y chromosomes for the presence or absence of many DNA loci. The individuals studied included XX males, XY females, and persons in whom chromosome banding had revealed translocated, deleted, isodicentric, or ring Y chromosomes. Most of the 132 Y chromosomal loci mapped were sequence-tagged sites, detected by means of the polymerase chain reaction. These studies resolved the euchromatic region (short arm, centromere, and proximal long arm) of the Y chromosome into 43 ordered intervals, all defined by naturally occurring chromosomal breakpoints and averaging less than 800 kilobases in length. This deletion map should be useful in identifying Y chromosomal genes, in exploring the origin of chromosomal disorders, and in tracing the evolution of the Y chromosome. PMID- 1439770 TI - A comprehensive genetic linkage map of the human genome. NIH/CEPH Collaborative Mapping Group. AB - A genetic linkage map of the human genome was constructed that consists of 1416 loci, including 279 genes and expressed sequences. The loci are represented by 1676 polymorphic systems genotyped with the CEPH reference pedigree resource. A total of 339 microsatellite repeat markers assayed by PCR are contained within the map, and of the 351 markers with heterozygosities of at least 70%, 205 are microsatellites. Seven telomere loci define physical and genetic endpoints for 2q, 4p, 7q, 8p, 14q, 16p, and 16q, and in other cases distal markers on the maps have been localized to terminal cytogenetic bands. Therefore, at least 92% of the autosomal length of the genome and 95% of the X chromosome is estimated to be spanned by the map. Since the maps have relatively high marker density and numerous highly informative loci, they can be used to map disease phenotypes, even for those with limited pedigree resources. The baseline map provides a foundation for achieving continuity of clone-based physical maps and for the development of a truly integrated physical, genetic, and cytogenetic map of the human. PMID- 1439771 TI - Genome maps III. 1992. Wall Chart. PMID- 1439772 TI - Pioneering work in immune tolerance. PMID- 1439773 TI - Panel set to critique AIDS vaccine award. PMID- 1439774 TI - Breast cancer's forced march? PMID- 1439775 TI - Women's health issues take center stage at the IOM. PMID- 1439776 TI - NIH fends off critics of tamoxifen study. PMID- 1439777 TI - Three physicians convicted in French 'blood-supply trial'. PMID- 1439779 TI - Panel nixes Congo trials as AIDS source. PMID- 1439778 TI - A consensus on reform begins to take shape. PMID- 1439780 TI - The Huntington's gene quest goes on. PMID- 1439781 TI - Supercomputers image the body in three dimensions. PMID- 1439782 TI - Actin constitution: guaranteeing the right to assemble. PMID- 1439783 TI - What if Minkowski had been ageusic? An alternative angle on diabetes. AB - Despite decades of intensive investigation, the basic pathophysiological mechanisms responsible for the metabolic derangements associated with diabetes mellitus have remained elusive. Explored here is the possibility that traditional concepts in this area might have carried the wrong emphasis. It is suggested that the phenomena of insulin resistance and hyperglycemia might be more readily understood if viewed in the context of underlying abnormalities of lipid metabolism. PMID- 1439784 TI - Resonance-enhanced x-rays in thin films: a structure probe for membranes and surface layers. AB - An x-ray resonance effect in an organic thin film on an x-ray reflecting mirror is reported. The resonance effect is the result of interference between reflected and refracted x-rays at the air-organic thin film interface and occurs at incident angles slightly above the critical angle of the film. In excellent agreement with theory, the primary resonant x-ray electric field that is confined in the organic thin film is approximately 20 times as intense as the electric field of the incident beam when measured at a position close to the center of the film. Resonance-enhanced x-rays can be used to characterize the internal structure of Langmuir-Blodgett thin film membranes. This effect may also find use in x-ray-based thin film devices and in the structural analysis of adlayers and surfaces that have thus far proved difficult, if not impossible, to study because of sensitivity limitations. PMID- 1439785 TI - Submicrometer intracellular chemical optical fiber sensors. AB - A thousandfold miniaturization of immobilized optical fiber sensors, a millionfold or more sample reduction, and at least a hundredfold shorter response time, all simultaneously, were achieved by combining nanofabricated optical fiber tips with near-field photopolymerization. Specifically, pH optical fiber sensors were prepared with internal calibration, making use of the differences in both fluorescence and absorption of the acidic and basic dye species. The submicrometer sensors have excellent detection limits, as well as photostability, reversibility, and millisecond response times. Successful applications include intracellular and intraembryonic measurements. Potential applications include spatially and temporally resolved chemical analysis and kinetics inside single biological cells and their substructures. PMID- 1439786 TI - Homobatrachotoxin in the genus Pitohui: chemical defense in birds? AB - Three passerine species in the genus Pitohui, endemic to the New Guinea subregion, contain the steroidal alkaloid homobatrachotoxin, apparently as a chemical defense. Toxin concentrations varied among species but were always highest in the skin and feathers. Homobatrachotoxin is a member of a class of compounds collectively called batrachotoxins that were previously considered to be restricted to neotropical poison-dart frogs of the genus Phyllobates. The occurrence of homobatrachotoxin in pitohuis suggests that birds and frogs independently evolved this class of alkaloids. PMID- 1439787 TI - Saltation and stasis: a model of human growth. AB - Human growth has been viewed as a continuous process characterized by changing velocity with age. Serial length measurements of normal infants were assessed weekly (n = 10), semiweekly (n = 18), and daily (n = 3) (19 females and 12 males) during their first 21 months. Data show that growth in length occurs by discontinuous, aperiodic saltatory spurts. These bursts were 0.5 to 2.5 centimeters in amplitude during intervals separated by no measurable growth (2 to 63 days duration). These data suggest that 90 to 95 percent of normal development during infancy is growth-free and length accretion is a distinctly saltatory process of incremental bursts punctuating background stasis. PMID- 1439788 TI - Antibody-catalyzed rearrangement of the peptide bond. AB - The generation of antibodies from a bifunctional cyclic phosphinate transition state analog provided agents capable of efficiently catalyzing both steps of the overall conversion of a substrate containing an asparaginyl-glycyl sequence through a succinimide intermediate to the products aspartyl-glycyl and the rearranged isoaspartyl-glycyl sequence. This reaction provides a potential means in addition to amide cleavage for the deactivation of protein or peptide biological functions in vivo. PMID- 1439789 TI - Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. AB - Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD), two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asn178) of the prion protein gene. The possibility that a second genetic component modified the phenotypic expression of the Asn178 mutation was investigated. FFI and the familial CJD subtype segregated with different genotypes determined by the Asn178 mutation and the methionine-valine polymorphism at codon 129. The Met129, Asn178 allele segregated with FFI in all 15 affected members of five kindreds whereas the Val129, Asn178 allele segregated with the familial CJD subtype in all 15 affected members of six kindreds. Thus, two distinct disease phenotypes linked to a single pathogenic mutation can be determined by a common polymorphism. PMID- 1439790 TI - Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. AB - In a screen for transcriptional regulators that control differentiation into the T cell lineage, a complementary DNA was isolated encoding a zinc finger protein (Ikaros) related to the Drosophila gap protein Hunchback. The Ikaros protein binds to and activates the enhancer of a gene encoding an early T cell differentiation antigen, CD3 delta. During development, Ikaros messenger RNA was first detected in the mouse fetal liver and the embryonic thymus when hematopoietic and lymphoid progenitors initially colonize these organs; no expression was observed in the spleen or the bone marrow. The pattern of Ikaros gene expression and its ability to stimulate CD3 delta transcription support the model that Ikaros functions in the specification and maturation of the T lymphocyte. PMID- 1439791 TI - A GDP dissociation inhibitor that serves as a GTPase inhibitor for the Ras-like protein CDC42Hs. AB - Members of the family of Ras-related guanosine triphosphate (GTP) binding proteins appear to take part in the regulation of a number of biological processes, including cell growth and differentiation. Three different classes of proteins that regulate the GTP binding and GTP hydrolytic activities of the Ras family members have been identified. These different regulatory proteins inhibit guanosine diphosphate (GDP) dissociation (designated as GDIs), stimulate GDP dissociation and GDP-GTP exchange (designated as GDSs), or stimulate GTP hydrolysis (designated as GAPs). In the case of the Ras-like protein CDC42Hs, which is the human homolog of a Saccharomyces cerevisiae cell division cycle protein, the GDI protein also inhibited both the intrinsic and GAP-stimulated hydrolysis of GTP. These findings establish an additional role for the GDI protein--namely, as a guanosine triphosphatase (GTPase) inhibitory protein for a Ras-like GTP binding protein. PMID- 1439792 TI - Selecting T cell receptors with high affinity for self-MHC by decreasing the contribution of CD8. AB - Selective events during T cell repertoire development in the thymus include both the positive selection of cells whose receptors recognize self-major histocompatibility complex (MHC) molecules and negative selection (tolerance) of cells whose interaction with self-MHC is of high affinity. The affinity of T cell interactions with class I MHC molecules includes contributions by both the T cell receptor and the CD8 coreceptor. Therefore, by decreasing the affinity of the interaction with CD8, T cells whose receptors have relatively high affinities for self-MHC may survive negative selection. Such T cells were generated and those T cells reactive with self-MHC plus antigen also displayed low affinity for self. PMID- 1439793 TI - A surface protease and the invasive character of plague. AB - A 9.5-kilobase plasmid of Yersinia pestis, the causative agent of plague, is required for high virulence when mice are inoculated with the bacterium by subcutaneous injection. Inactivation of the plasmid gene pla, which encodes a surface protease, increased the median lethal dose of the bacteria for mice by a millionfold. Moreover, cloned pla was sufficient to restore segregants lacking the entire pla-bearing plasmid to full virulence. Both pla+ strains injected subcutaneously and pla- mutants injected intravenously reached high titers in liver and spleen of infected mice, whereas pla- mutants injected subcutaneously failed to do so even though they establish a sustained local infection at the injection site. More inflammatory cells accumulated in lesions caused by the pla- mutants than in lesions produced by the pla+ parent. The Pla protease was shown to be a plasminogen activator with unusual kinetic properties. It can also cleave complement C3 at a specific site. PMID- 1439794 TI - Cellular membranes. PMID- 1439795 TI - Electrical measurements on endomembranes. PMID- 1439796 TI - NIH's strategic planning Rorschach blot. PMID- 1439797 TI - AIDS vaccines. Army investigates researcher's report of clinical trial data. PMID- 1439798 TI - Science in Ireland. Brussels provides funding lifeline to Irish research. PMID- 1439799 TI - FDA sets out to hire 600--and image is a problem. PMID- 1439800 TI - How scary things get that way. PMID- 1439801 TI - Neuroscience fantasia in an appropriate setting. PMID- 1439802 TI - Race quickens for non-stick blood monitoring technology. PMID- 1439803 TI - Membrane fusion. AB - Common themes are emerging from the study of viral, cell-cell, intracellular, and liposome fusion. Viral and cellular membrane fusion events are mediated by fusion proteins or fusion machines. Viral fusion proteins share important characteristics, notably a fusion peptide within a transmembrane-anchored polypeptide chain. At least one protein involved in a cell-cell fusion reaction resembles viral fusion proteins. Components of intracellular fusion machines are utilized in multiple membrane trafficking events and are conserved through evolution. Fusion pores develop during and intracellular fusion events suggesting similar mechanisms for many, if not all, fusion events. PMID- 1439804 TI - The annexins and exocytosis. AB - The annexins are a group of homologous proteins that bind phospholipids in the presence of calcium. They may provide a major pathway for communication between cellular membranes and their cytoplasmic environment. Annexins have a characteristic "bivalent" activity in the sense that they can draw two membranes together when activated by calcium. This has led to the hypothesis that certain members of this protein family may initiate contact and fusion between a secretory vesicle membrane and the plasma membrane during the process of exocytosis. PMID- 1439805 TI - The nuclear membrane. AB - The nuclear membrane forms a major barrier within the cell, permitting levels of regulation not found in prokaryotes. The dynamics and diverse functions of the nuclear membrane and its associated structures are considered in this review. The role of the nuclear pore complex in selective transport across the nuclear membrane has been studied to a considerable degree; however, many crucial questions remain. Components of a signal transduction mechanism are associated with the nucleus, suggesting that nuclear functions may be influenced directly by this system. The involvement of the heat shock cognate protein Hsc70 in nuclear protein import is discussed, and a specific signal-presentation role for this protein is proposed. PMID- 1439806 TI - Regulation of cell surface polarity from bacteria to mammals. AB - The generation of unique domains on the cell, cell surface polarity, is critical for differentiation into the diversity of cell structures and functions found in a wide variety of organisms and cells, including the bacterium Caulobacter crescentus, the budding yeast Saccharomyces cerevisiae, and mammalian polarized epithelial cells. Comparison of the mechanisms for establishing polarity in these cells indicates that restricted membrane protein distributions are generated by selective protein targeting to, and selective protein retention at, the cell surface. Initiation of these mechanisms involves reorientation of components of the cytoskeleton and protein transport pathways toward restricted sites at the cell surface and formation of a targeting patch at those sites for selective recruitment and retention of proteins. PMID- 1439807 TI - Cytoskeleton--plasma membrane interactions. AB - Proteins at the boundary between the cytoskeleton and the plasma membrane control cell shape, delimit specialized membrane domains, and stabilize attachments to other cells and to the substrate. These proteins also regulate cell locomotion and cytoplasmic responses to growth factors and other external stimuli. This diversity of cellular functions is matched by the large number of biochemical mechanisms that mediate the connections between membrane proteins and the underlying cytoskeleton, the so-called membrane skeleton. General organizational themes are beginning to emerge from examination of this biochemical diversity. PMID- 1439808 TI - Selectins: interpreters of cell-specific carbohydrate information during inflammation. AB - Although a bewildering array of cell surface carbohydrate structures have been described, the physiological relevance of any of these complex molecules has often eluded biologists. A family of cell surface glycoproteins, the "selectins," has a characteristic ability to use some of these carbohydrate structures in adhesive mechanisms that help localize leukocytes to regions of inflammation. This article will review the biology of these carbohydrate-binding adhesive proteins and discuss the potential for developing anti-inflammatory antagonists that could inhibit binding events that are selectin-mediated. PMID- 1439809 TI - Chemical contrast in X-ray microscopy and spatially resolved XANES spectroscopy of organic specimens. AB - The scanning transmission x-ray microscope at the National Synchrotron Light Source has been used to record x-ray absorption near-edge structure (XANES) spectra from 0.01-square-micrometer regions of organic specimens. The spectral features observed reflect the molecular structure of the dominant absorbing atoms and provide the contrast mechanism for high-resolution imaging with chemical sensitivity. This technique was used with x-ray energies near the carbon K absorption edge to identify and map separate phases in various polymer blends and to map the DNA distribution in chromosomes with a spatial resolution of 55 nanometers. PMID- 1439811 TI - European research institutes. PMID- 1439810 TI - Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. AB - Abetalipoproteinemia is a human genetic disease that is characterized by a defect in the assembly or secretion of plasma very low density lipoproteins and chylomicrons. The microsomal triglyceride transfer protein (MTP), which is located in the lumen of microsomes isolated from the liver and intestine, has been proposed to function in lipoprotein assembly. MTP activity and the 88 kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects. This finding suggests that a defect in MTP is the basis for abetalipoproteinemia and that MTP is indeed required for lipoprotein assembly. PMID- 1439812 TI - UV light exposure and HIV replication. PMID- 1439813 TI - Clinton's technology agenda. PMID- 1439814 TI - AIDS funding. MicroGeneSys vaccine trial gets a public peer review. PMID- 1439815 TI - Closing in on melanoma susceptibility gene(s) PMID- 1439816 TI - Cell biology. A new kind of organic gardening. PMID- 1439817 TI - Playing 'telephone' with the body's message of pain. PMID- 1439818 TI - Prevalence of AIDS-related risk factors and condom use in the United States. AB - A national probability survey of human immunodeficiency virus (HIV)-related risk factors among the general heterosexual population, the National AIDS (acquired immunodeficiency syndrome) Behavioral Surveys, has obtained data from 10,630 respondents. Data are presented on the prevalence of HIV-related risks in the general heterosexual population, on the distribution of the three largest risk groups across social strata, and on the prevalence and distribution of condom use among heterosexuals reporting a risk factor. Between 15 and 31 percent of heterosexuals nationally and 20 and 41 percent in cities with a high prevalence of AIDS reported an HIV risk factor. Condom use was relatively low. Only 17 percent of those with multiple sexual partners, 12.6 percent of those with risky sexual partners, and 10.8 percent of untested transfusion recipients used condoms all the time. Overall, the results suggest that current HIV prevention programs have, to a very limited extent, reached those heterosexuals with multiple sexual partners but have failed to reach many other groups of the heterosexual population at risk for HIV. New public health strategies may be needed for these specific risk groups. PMID- 1439819 TI - Direct mechanical measurements of the elasticity of single DNA molecules by using magnetic beads. AB - Single DNA molecules were chemically attached by one end to a glass surface and by their other end to a magnetic bead. Equilibrium positions of the beads were observed in an optical microscope while the beads were acted on by known magnetic and hydrodynamic forces. Extension versus force curves were obtained for individual DNA molecules at three different salt concentrations with forces between 10(-14) and 10(-11) newtons. Deviations from the force curves predicted by the freely jointed chain model suggest that DNA has significant local curvature in solution. Ethidium bromide and 4',6-diamidino-2-phenylindole had little effect on the elastic response of the molecules, but their extent of intercalation was directly measured. Conversely, the effect of bend-inducing cis diamminedichloroplatinum (II) was large and supports the hypothesis of natural curvature in DNA. PMID- 1439820 TI - The evolutionary convergence of hearing in a parasitoid fly and its cricket host. AB - Parasitism is a widespread and diverse life strategy that connects species throughout the animal kingdom. Female parasitoid flies of the genus Ormia must find a specific cricket host on which to deposit their parasitic maggots. To reproduce, female flies must perform the same task as female crickets: find a singing male cricket. These flies have evolved a unique hearing organ that allows them to detect and locate singing male crickets. Through evolutionary convergence, these flies possess a hearing organ that much more resembles a cricket's ear than a typical fly's ear, allowing these parasitoids to take advantage of the sensory ecological niche of their host. PMID- 1439821 TI - Cooperativity induced by a single mutation at the subunit interface of a dimeric enzyme: glutathione reductase. AB - When glycine418 of Escherichia coli glutathione reductase, which is in a closely packed region of the dimer interface, is replaced with a bulky tryptophan residue, the enzyme becomes highly cooperative (Hill coefficient 1.76) for glutathione binding. The cooperativity is lost when the mutant subunit is hybridized with a wild-type subunit to create a heterodimer. The mutation appears to disrupt atomic packing at the dimer interface, which induces a change of kinetic mechanism. A single mutation in a region of the protein remote from the active site can thus act as a molecular switch to confer cooperativity on an enzyme. PMID- 1439822 TI - In vitro transcriptional activation by a metabolic intermediate: activation by Leu3 depends on alpha-isopropylmalate. AB - In the absence of the leucine biosynthetic precursor alpha-isopropylmalate (alpha IPM), the yeast LEU3 protein (Leu3p) binds DNA and acts as a transcriptional repressor in an in vitro extract. Addition of alpha-IPM resulted in a dramatic increase in Leu3p-dependent transcription. The presence of alpha-IPM was also required for Leu3p to compete effectively with another transcriptional activator, GAL4/VP16, for limiting transcription factors. Therefore, the addition of alpha IPM appears to convert a transcriptional repressor into an activator. This represents an example in eukaryotes of direct transcriptional regulation by a small effector molecule. PMID- 1439823 TI - Bacteriophage lambda PaPa: not the mother of all lambda phages. AB - The common laboratory strain of bacteriophage lambda--lambda wild type or lambda PaPa--carries a frameshift mutation relative to Ur-lambda, the original isolate. The Ur-lambda virions have thin, jointed tail fibers that are absent from lambda wild type. Two novel proteins of Ur-lambda constitute the fibers: the product of stf, the gene that is disrupted in lambda wild type by the frameshift mutation, and the product of gene tfa, a protein that is implicated in facilitating tail fiber assembly. Relative to lambda wild type, Ur-lambda has expanded receptor specificity and adsorbs to Escherichia coli cells more rapidly. PMID- 1439825 TI - B cells turn off virgin but not memory T cells. AB - There are three possible outcomes when a T cell recognizes a cell bearing a self or foreign antigen. (i) The T cell is not sufficiently signaled and is unaffected. (ii) The T cell is activated. (iii) The T cell is turned off. The differentiation state of the T cell is critical to the outcome. Although both virgin and memory T cells can be activated by antigens presented by "professional" antigen-presenting cells such as dendritic cells, they differ in their responses to B cells. Experienced T cells respond to antigen presented by B cells, whereas virgin T cells are rendered tolerant. These findings may relate to the phenomena of low- and high-zone tolerance, neonatal tolerance, and the beneficial effect of blood transfusions on allograft survival. PMID- 1439824 TI - Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. AB - Linkage analysis of ten Utah kindreds and one Texas kindred with multiple cases of cutaneous malignant melanoma (CMM) provided evidence that a locus for familial melanoma susceptibility is in the chromosomal region 9p13-p22. The genetic markers analyzed reside in a candidate region on chromosome 9p21, previously implicated by the presence of homozygous deletions in melanoma tumors and by the presence of a germline deletion in an individual with eight independent melanomas. Multipoint linkage analysis was performed between the familial melanoma susceptibility locus (MLM) and two short tandem repeat markers, D9S126 and the interferon-alpha (IFNA) gene, which reside in the region of somatic loss in melanoma tumors. An analysis incorporating a partially penetrant dominant melanoma susceptibility locus places MLM near IFNA and D9S126 with a maximum location score of 12.71. Therefore, the region frequently deleted in melanoma tumors on 9p21 presumably contains a locus that plays a critical role in predisposition to familial melanoma. PMID- 1439826 TI - Perceptual correlates of massive cortical reorganization. PMID- 1439827 TI - Structural similarity between transforming growth factor-beta 2 and nerve growth factor. PMID- 1439828 TI - Minorities in science. PMID- 1439829 TI - What went wrong: why programs failed. PMID- 1439830 TI - Identity crisis: teaching v. research. PMID- 1439831 TI - Asian-Americans bump against glass ceilings. PMID- 1439832 TI - Sequencing and computer time. PMID- 1439833 TI - Dividing up the neocortex. PMID- 1439834 TI - The progress of science. PMID- 1439835 TI - In biotechnology, Japanese yen for American expertise. PMID- 1439836 TI - In search of the human touch. PMID- 1439837 TI - Unraveling the dark paradox of 'blindsight'. PMID- 1439838 TI - Post-transcriptional regulation of early T cell development by T cell receptor signals. AB - During differentiation in the thymus, immature T cells progress through an ordered sequence of developmental stages that are best characterized by variable expression of the co-receptor molecules CD4 and CD8. Crosslinking of T cell receptor (TCR) molecules on precursor thymocytes was found to block their differentiation into CD4+CD8+ cells by eliminating messenger RNA's encoding two families of developmentally important molecules: the co-receptor molecules CD4 and CD8 and the recombination activating genes 1 and 2. TCR-induced post transcriptional regulation in early thymocytes was specific for selective messenger RNA's, required protein synthesis, and was itself developmentally regulated. These data identify a post-transcriptional mechanism that is influenced by TCR signals and that regulates early thymocyte development. PMID- 1439839 TI - Residual vision in a scotoma: implications for blindsight. AB - Blindsight, the ability of some blind patients to describe attributes of stimuli they have no conscious awareness of seeing, has been attributed to a secondary (retinotectal) visual pathway. However, it has also been proposed that blindsight could be due to residual function within the primary (geniculostriate) visual pathway. Data have now been obtained that support the second alternative. With an image stabilizer ensuring the accurate retinal placement of stimuli, dense visual field mapping was carried out with a hemianopic patient. This perimetry revealed, embedded in the patient's scotoma, an isolated 1-degree island of residual vision that was not disclosed by conventional perimetric methods. Stimuli presented to this island could be detected and discriminated, although the subject reported he did not see them. The existence of this island of vision implies a corresponding island of functioning cortex within the patient's lesion. Other instances of blindsight may be mediated by similar islands of functioning cortex. PMID- 1439841 TI - Science Innovation meeting 1992. San Francisco. Abstracts. PMID- 1439840 TI - Guide to scientific products, instruments and services. Product listing. PMID- 1439842 TI - Posterior tibial tendon dysfunction. AB - Posterior tibial tendon dysfunction, a common entity, frequently is unrecognized and inappropriately managed. Acutely, pain and swelling are present over the medial ankle and longitudinal arch. Long-standing inflammation can lead to tendon rupture, resulting in a progressive planovalgus or "flat foot" deformity. Plain radiographs illustrate the changes in bony anatomy associated with chronic posterior tibial deficiency, while magnetic resonance imaging scans can identify the three stages of posterior tibial tendon pathology. Most cases are amenable to conservative therapy, including rest and administration of nonsteroidal antiflammatory agents. Often a short period of immobilization in a cast or the use of an orthosis is beneficial. In cases with persistent tenosynovitis, complete tendon rupture, or progressive deformity, surgical intervention is indicated. PMID- 1439843 TI - Primary Sjogren's syndrome--clinical and laboratory markers of disease activity. AB - Primary Sjogren's syndrome is a chronic autoimmune disorder of the lacrimal and salivary glands, reflecting general involvement of the exocrine tissues and leading to functional impairment. This polyglandular disease is often associated with systemic extraglandular manifestations, and laboratory tests usually indicate polyclonal B-lymphocyte hyperactivity. Clinical and laboratory markers monitoring the disease processes are needed for improved management of primary Sjogren's syndrome. However, incomplete knowledge of the long-term course of inflammation as well as of clinical manifestations makes precise and simple directions for monitoring disease activity in primary Sjogren's syndrome difficult. This review describes potential primary (eg, salivary gland histopathology, autoantibodies, soluble interleukin-2 receptors, and beta 2 microglobulin) and secondary disease activity markers (clinical and laboratory signs of glandular and extraglandular organ damage) and their known associations. The importance of genetic characteristics, patient age, and symptom duration for the disease activity markers is indicated. The systematic use of primary and secondary disease activity markers will improve our understanding of primary Sjogren's syndrome and help create better guidelines for monitoring the disease. PMID- 1439844 TI - A clinical, serological, and histopathological study of myositis patients with and without anti-RNP antibodies. AB - Twenty-nine patients with myositis, including 10 with polymyositis (PM), 6 with dermatomyositis (DM), and 13 with myositis associated with a connective tissue disease (CTD), were followed up for a mean observation time of 49 months. The 13 patients with CTD-associated myositis were further separated by the presence or absence of anti-RNP antibodies. The functional disability at diagnosis was pronounced without differences between the groups. The patients with anti-RNP antibodies did not differ from the other patients regarding initial muscle weakness, erythrocyte sedimentation rate, or creatinine phosphokinase values, but the histopathological muscle changes were generally milder. Rapid improvement of muscle strength on moderate doses of corticosteroids was seen in most patients. At the end of study, corticosteroid treatment had been withdrawn from 17 patients because of remission, including 6 of the 7 patients with anti-RNP antibodies. The presence of electromyographic changes compatible with myositis, pronounced muscle weakness before treatment, and a low erythrocyte sedimentation rate seemed to indicate a less favorable outcome unrelated to diagnostic subgroupings. However, the combination was rarely found among the anti-RNP-positive patients. PMID- 1439845 TI - Amyloidosis. AB - Amyloidosis is a heterogenous group of diseases characterized by deposition of a fibrillar, proteinaceous material, amyloid, in various tissues and organs. Increasing knowledge about the different proteins that constitute the amyloid fibrils has made it possible to classify amyloidosis by the fibril protein, which appears more rational than the traditional classification by its clinical expression. A serum protein is the precursor of the amyloid fibril protein in the various systemic forms of amyloidosis. Although the chemical composition of amyloid is presently well known, the pathogenetic processes that convert such proteins into a fibrillar form and lay them down in the tissues are far from clarified. This review describes the amyloid deposits, some putative pathogenetic mechanisms, and the clinical, therapeutic, and prognostic aspects of the most important forms of amyloid disease. PMID- 1439846 TI - Timed treatment of the arthritic diseases: a review and hypothesis. AB - Evidence has been accumulating regarding the importance of biological rhythms in the diagnosis and treatment of a variety of diseases and disorders. Increasingly, the arthritides have shown statistically quantifiable rhythmic parameters. Included in the latter group are joint pain and joint size. In addition, a number of drugs used to treat rheumatic diseases have varying therapeutic and toxic effects based on the time of day of administration. Among these drug classes are nonsteroidal antiinflammatory drugs, glucocorticoids, and a number of cytostatic agents. In the last group of agents, experience in treating malignant disease suggests that time-specified treatment may reduce the toxic effects of low-dose cytostatic treatment of rheumatoid arthritis (RA) and related diseases. This article reviews that evidence and suggests a rationale for the timed treatment of RA with methotrexate. PMID- 1439847 TI - Transient osteoporosis of the hip. AB - Transient osteoporosis of the hip (TOH) is an uncommon but possibly underdiagnosed condition. This pattern of regional osteoporosis affects previously healthy middle-aged men, and women in the third trimester of pregnancy. Its etiology is still unclear, yet in view of similarities to regional migratory osteoporosis and reflex sympathetic dystrophy, vascular and neurologic disturbances have been proposed as the possible pathogenetic mechanisms. Pain in the hip area and functional disability of the affected limb are the main clinical signs. Diagnosis is supported by local radiological osteopenia whose gradual disappearance parallels the spontaneous recovery. Bone scintigraphy, magnetic resonance imaging, computed tomography, and other imaging methods are supplementary diagnostic tools. Exclusion of more common entities is required. The purpose of this report is to elucidate the diagnostic and therapeutic aspects of TOH and to stimulate the physician's awareness of this condition, recognition of which may prevent unnecessary invasive procedures and inadequate treatment. PMID- 1439848 TI - [Impotence from the 70's through the 90's: 20 years of evolution of diagnosis and therapy]. AB - The surgical treatment of vascular impotence has evolved as our understanding of the haemodynamics of erection advanced. In the early Seventies the direct revascularization techniques which create an anastomosis between an artery and the corpora cavernosa came to be so much in use that an era of so-called "pure arteriogenic impotence" seemed to be dawning. An arterial role in the pathogenesis of importance gained increasing support during that decade, as the use of a number of techniques for the diagnostic assessment of penile haemodynamics becomes widespread (Doppler ultrasound, determination of the penile brachial index, selective hypogastric arteriography, penile radionuclide scan, penile plethysmography). Corpora cavernosa-direct revascularization techniques, such as the Epigastric-Corporal and Femoro-Corporal trans-Saphena anastomoses, were developed, the latter being proposed by Michal in 1973. By the late Seventies, however, most Authors had abandoned these techniques. Severe haemodynamic side-effects, such as uninterrupted intra-cavernous high pressure and attendant permanent tumescence of penis, were found to induce the microfibrosis of erectile tissues and the thrombosis at the site of the anastomosis. In this period, "venous leakage" became, with the advent of cavernosography, a recognized factor in the pathogenesis of impotence. However, the concept of venogenic impotence, characterized as it is by transient erection, and featuring pathological cavernosograms as well as high cavernometric figures, belongs more appropriately to a clinical syndrome and is, therefore far from being unambiguous. Arterial-arterial bypass and selective veins ligation were then introduced to treat cases of "pure" arteriogenic or venogenic insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439849 TI - [Endocrine therapy of sexual impotence in men]. AB - Male sexual activity is in all mammalian species, included man, androgen dependent. The role of testosterone (T) starts already during intrauterine life. It continues thereafter, inducing the development of sexual secondary characteristics and libido. Therefore T has represented the "classical" treatment of male sexual dysfunctions. In the therapeutic routinary use T is employed ad ester, like cipionate, enanthate and other i.m., undecanoate per os. When a pituitary defect is present and the testicular receptors are functioning a treatment with HCG can be employed. PMID- 1439850 TI - [Medical treatment and impotence]. AB - After having emphasized the importance of interdisciplinary diagnostic approach to the sexual impotence as a symptom and having made some comments about the erection's physiology, the Authors, according to their experience, take drugs into consideration for elective treatment of sexual intercourse. PMID- 1439851 TI - [Treatment of psychogenic impotence]. AB - Individual, marital or familiar problems, life circumstances, lack of libido, anxiety or sex identity fragility or immaturity may determine or make worse the erectile deficit. A thorough diagnostic work up is essential for the prognosis and the choice of the more fitting therapy. Emotional and cognitive understanding of the psychogenic background of the symptom is combined with behavioral therapy based on modern principles of neuroriabilitation. PMID- 1439852 TI - [Intracavernous infusion of drugs]. AB - In 1982 Virag presented the initial experience of use in diagnosis and treatment of impotence. PGE1 has been showed a safe and effectiveness drug. From september 1989 to october 1991 210 patients with erectile disorders were managed by I.C.I. with PGE1 with minimal side effects. PMID- 1439853 TI - [Non-surgical therapy of impotence: infiltration, iontophoresis, ultrasound, laser]. AB - Surgical therapy is the only useful correction in congenital fibrosis or in hypoplasia of the 'corpora cavernosa', associated with hypospadia or not. On the contrary in not congenital fibrosis of the 'corpora cavernosa' (Peyronie's disease, consequences of priapism, or trauma, complications of pharmaco prosthesis) are allowed pharmaco-physical treatments (infiltrations, ionophoresis, ultrasound, laser). Pharmaco-physical therapy can be used as the only treatment, which is often resolutive, but it is also useful before or after the surgical operation of the 'corpora cavernosa'. These diseases can give disorders of the erection, until complete impotence is reached. In fact the erectile tissue can't expand, because of the rising fibrosclerosis. Among acquired fibrosis of corpora cavernosa I.P.P. has surely the greatest recurrent: the consistency of our series made possible to achieve significant results with a unified therapeutical protocol. The same management was applied in other, less frequent, penile fibrosis, always with full positive results even if on a small number of patients. We are evaluating a new drug (defibrotide) in the treatment of cavernosal vasculitis. Another one (hyaluronidase) associated to orgotein, could improve its effect against inflammation especially in chronic evolutions. Besides new treatments, we emphasize the prevention of iatrogenic fibrosis with particular regard to cavernous pharmaco-infusions by autoinjections: the training of the patient and the safety of the autoinjectors must be carefully checked by the andrologist to decrease a large amount of complications. PMID- 1439854 TI - [Transdermal therapy of erectile insufficiency]. AB - The introduction of intracavernosal (i.c.) administration of vasoactive drugs has revolutionized diagnosis and treatment of sexual impotence. This procedure, though, carries some risks and undesired side-effects, such as fibrosis, priapism, hematomas, etc. Thus, at our Centre has been evaluated the possibility of a transdermal (TS), either active or passive, treatment of impotence. In a first trial, double blind crossover, 62 patients have been treated with yohimbine (YOH) as ointment. About 5 mg of the drug were applied at the balanopreputial sulcus, twice daily. In 10 patients YOH was also assayed by HPLC in the blood drawn from the corpora cavernosa after the application of the drug: a rapid adsorption of the drug was demonstrated and a peak value of 58 ng/ml at 25 min. Treatment with YOH was particularly satisfactory in patients with impotence of recent onset and mild degree, that is without major vascular alterations. The active TD drug administration was tested with papaverine delivered with cavernous bodies by a C.T.D.A.S. (Controlled Transdermal Drugs Administration System). Thin layer chromatography has shown the passage of about 10% of patients a relevant amelioration of erectile function was observed. PMID- 1439855 TI - [Vacuum therapy]. AB - In the therapy of vasculogenic impotence, the Vacuum Device has been proposed up to now as an "external" prosthesis device with the aim of obtaining a penile erection of sufficient rigidity for penetration, in patients afflicted by vascular or neurological disorders. In the eighties, the experience gained with the use of Intra Cavernous Injections (C.I.D.) (using papaverine, phentolamine and prostaglandin), demonstrated not to be an exclusively palliative therapy ("pharmacological prosthesis"), but to represent as well a sort of "vasoactive exercise" of the erectile tissue. In the nineties, many wondered what could be a valid alternative to the C.I.D. Taking this into consideration, we modified the method of application of Vacuum Therapy. The device was used once a day without the constrictive band applied to the penis root, in order to generate a passive action on the erectile tissue, a sort of "stretching" for the smooth muscle fibers. From January 1990 to December 1991, we treated 78 pts. afflicted by erectile failure. The patients were divided into 3 groups (26 each) of distinct therapy: the first was treated weekly with only endocavernous papaverine administration (20 mg.), the second underwent daily Vacuum Therapy exclusively (10'-15') and the third received a combined therapy: Vacuum Device, daily and C.I.D. with Papaverine (20 mg.) once a week. The results of this treatment are as follows: the patients who underwent Vacuum Therapy daily (2nd and 3rd groups) showed, at the end of the treatment (6 months), a significant improvement in spontaneous erectile ability (14 Pts.-53.8% in the 2nd group; 17 Pts-65.3% in the 3rd group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439856 TI - [Postoperative impotence]. AB - Increasing interest has developed in recent years about the preservation of sexual function after urological surgery. The pelvic plexus which is formed by parasympathetic visceral efferent preganglionic fibers that arise from the sacral center provides autonomic innervation to the corpora cavernosa. The cavernous nerves emerge from the pelvic plexus and then travel along the posterolateral portion of the seminal vesicle and prostate and then along the membranous urethra. The preservation of the nerve supply of the corpora during urological and pelvic procedures is of vital importance to preserve potency. PMID- 1439857 TI - [Treatment of gas gangrene. Results of a retro- and prospective analysis of a traumatologic patient sample over 20 years]. AB - From 1970 to 1977 and from 1978 to 1990, the treatment and outcome in 136 patients with gas gangrene were investigated. The prognosis was better in patients with gas gangrene after trauma than in patients with gas gangrene resulting from vascular insufficiency or malignant tumours. In the first group the lethality of gas gangrene was 28.6%, in the second group, 7.1%. This difference is significant (P < 0.05). In 40.5% the infected extremities were saved. Patients with injuries without fractures did not lose limbs because of gas gangrene or die of it. When an operation was performed before or after the first session of oxygenation at high pressure (OHP) lethality was lower (20%) and the rate of saved limbs higher (80%) than with later operation (lethality, 50%; saved limbs, 45.5%). All patients who could not be treated by OHP, or only once or twice, died. From 1970 to 1977 patients who were treated surgically and received OHP for 5 days survived, and since 1978 this has applied to patients treated for 4 days. In general, the lives of patients with gas gangrene are no longer in danger by the 5th day of therapy. The use of checklists for diagnosis and therapy has been practised since 1978, and this is assumed to be one factor in the better outcome. PMID- 1439858 TI - [Experimental studies of thermal disinfection and sterilization of allogeneic bone transplants and their effects on biological viability]. AB - Thermal energy (80 degrees) for the disinfection of cancellous allogenic bone grafts was employed, and it proved to be an advantageous, safe and easily accessible method. The effects of this treatment on biological values were examined in terms of biomechanical and biodynamic (graft incorporation) loss of the treated grafts versus the autoclaved and untreated samples. Given the thermolability of the pathogens in question, the thermal approach presented here has the advantage of being readily controllable. The lack of toxic or mutagenic risks through this method and its accessibility represent further advantages. In thermal treatment of bone allografts, it is essential that one knows the thermoconductivity of the bone sample and that one can demonstrate pathogen inactivation through the entire graft volume. All of the parameters in the 80 degrees C group that were measured in this study indicate clear biological superiority over the autoclaved group. A newly developed thermoincubator is introduced for gentler disinfection of allogenic bone grafts and it inactivates common vegetative pathogens as well as HIV. It is still necessary to conduct serological screening for hepatitis antigens in the donor pool, however. Based on these results, we conclude that the clinical use of autoclaved allogenic bone grafts needs to be reviewed and possibly limited. PMID- 1439859 TI - [HIV detection in the bone transplant with polymerase chain reaction]. AB - In trauma surgery, bone transplantation was needed in nearly 15% of all operations for reconstruction of defects. A high risk of viral infection remains in transplantation, however, cocultivation procedures have shown that human immunodeficiency virus (HIV-1) resides in bone of HIV-infected persons. Safety guidelines for running bone banks were not always easy to follow, and physical or chemical procedures applied for disinfection failed to inactivate HIV-1. In the present study we show that the polymerase chain reaction technique is an appropriate and sensitive means of detecting the HIV-1 genome in bone material prior to transplantation and-used in this way-can help to diminish the risk of HIV-1 transmission via bone transplantation. PMID- 1439860 TI - [MEDKOM--new perspectives for accident surgery?]. AB - MEDKOM is a new communication concept in trauma surgery, originally inaugurated as a multi-user online video communication system and now proving its benefits in medicine. The technological conditions needed and its daily usefulness are described, and examples from our clinic are given. The importance of modern technology and the possibilities it opens up, especially for medical training programmes and quality protection in trauma care, are pointed out. PMID- 1439861 TI - [Experimental trial of intraoperative spinal ultrasound]. AB - Dorsal operative stabilization of spinal fractures by internal fixation is an established means of treatment directed at releasing the extrinsic compression of the intraspinal contents caused by the fractured posterior surface of the vertebral body. There are few ways of assessing how successful the repositioning is intraoperatively. Intraoperative ultrasound with a special small transducer is possible, but it is difficult to reach the intraspinal area by this means, because it is surrounded by bones. A laminectomy would destabilize the injured vertebral column even further. By experiments performed on six human vertebral columns we show that it is possible to view the entire length of the fractured posterior surface by ultrasound. The beam has to be projected between the laminae vertebrae following a small laminotomy. Preliminary intraoperative experiences with eight patients confirm our experimental results. The intraoperative ultrasound results have been confirmed by preoperative and postoperative CT. We expect the necessity for laminectomy for examination of the posterior surface of the vertebral body to decline in frequency in the near future. PMID- 1439862 TI - [Temporary balloon catheter occlusion for control of bleeding of a blunt injury of the proximal axillary artery. Case report and review of the literature]. AB - We describe the successful placement of an intra-arterial balloon catheter by a femoral approach in order to occlude the proximal arterial end and to control massive bleeding in a patient with rupture of the left axillary artery after blunt scapulo-thoracic dissociation. To our knowledge this technique has so far not been reported in Europe. It allows rapid control of bleeding, minimizes blood loss and markedly facilitates pre- and perioperative management in selected cases. The authors review the relevant literature dealing with this topic. PMID- 1439863 TI - [Double dislocation of a finger (personal cases and contributions from the literature)]. AB - This is the author's third report on this extremely rare injury. New cases are discussed, and a review of observations is given on the basis of the author's experience and that of others. PMID- 1439864 TI - [Management of femoral neck fracture in advanced age using femur head endoprosthesis]. AB - Between 1984 and 1989, 419 patients with subcapital fracture were treated, 170 with a head conserving method, 57 with a total endoprosthesis (THR), and 242 with a hemiprosthesis. In the last group the average age was 80.1 (range 55-98) years. At follow up an average of 2.5 years after surgery 63.3% had died. Most of the remaining patients were asymptomatic and their walking ability in the first few years was good. Complications included head protrusion, followed in declining order of frequency by loosening and ectopic calcifications. We conclude that for elderly patients this technique is a suitable alternative to THR or the femoral head-conserving method, which had higher complication rates. PMID- 1439865 TI - [Results of repositioning osteotomies in delayed healing or pseudarthrosis of the proximal femur]. AB - The results after valgus osteotomy for delayed or nonunion in 20 patients with femoral neck fractures (9 Pauwels type II and 11 type III) and 10 intertrochanteric fractures are reported. The mean age of the patients at presentation with delayed/nonunion of femoral neck fractures and intertrochanteric fractures was 37.5 and 60 years, respectively. The average interval between injury and valgus osteotomy in the first and second group was 8 and 13 months, respectively. The average size of the preoperatively determined and intraoperatively removed wedge was 30 degrees in both groups. The results of the two fracture groups were analyzed separately. All but one osteotomy in a patient with a nonunion of a femoral neck fracture consolidated without complications. This case developed a nonunion at the osteotomy and required additional surgery consisting of bone graft and refixation to heal. Of the femoral neck delayed/nonunion cases, 15 (75%) healed immediately following valgus osteotomy. In the intertrochanteric delayed/nonunion patients, valgus osteotomy led directly to bone consolidation in 6 (60%). In each fracture group 3 additional cases healed following reoperation for a total consolidation rate of 90%. In the femoral neck group one union was complicated by infection, resulting in ankylosis of the hip and 3.5 years later another patient with a revascularized femoral head required total hip arthroplasty because of a large, loose osteochondral fragment. In two cases union of the former femoral neck fracture could not be achieved. Partial avascular necrosis determined the course and total hip arthroplasty was required for both cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439866 TI - [Arterial occlusive disease after surgical treatment of fractures of the lower extremity]. AB - Chronic arterial occlusive disease of the lower limb may complicate fracture treatment. In five cases, diagnosis of vascular disease was established when delayed fracture healing or skin gangrene occurred some weeks after operative fracture treatment. The diagnosis of vascular disease was made from the case history, examination of the patient and repeated pulse control at the feet. Arterial insufficiency will be worsened by long-term elevation of the leg and by fracture treatment with a cast or traction. Angiography is indicated, and quick vascular reconstruction is recommended. In one patient with known iliac occlusion (Leriche syndrome) we performed simultaneous vascular reconstruction and operative fracture treatment. PMID- 1439867 TI - Evaluation of coronary artery disease with positron emission tomography. AB - Positron emission tomography (PET) represents the most sophisticated imaging modality in nuclear medicine allowing quantification of regional tracer tissue concentrations. Beside the technical superiority of data acquisition, a large number of PET radiopharmaceuticals are available for clinical application. Based on currently available data, PET provides detection of coronary artery disease with higher diagnostic accuracy than conventional thallium-201 single positron emission computed tomography. Applications of PET with metabolic tracers have been shown to provide clinically important information in the management of patients with advanced coronary artery disease. Metabolic tissue characterization represents the most specific definition of tissue viability currently available. However, the relatively high cost of the technology and the lack of reimbursement by major insurance carriers has limited widespread clinical application. In addition to the acceptance of PET as an advanced clinical imaging modality, this imaging modality excels as a sophisticated research tool assessing specific tissue functions that could not be visualized before in the living human heart. Without doubt, this technique will contribute significantly to the future characterization of pathophysiological alterations in substrate metabolism and other physiological processes such as autonomic innervation. Furthermore, the kinetics of radiolabeled cardiac drugs may be studied with PET to provide objective characterization of cardiovascular drug effects and thus enhance our understanding of pharmacokinetics in the human heart. PMID- 1439868 TI - Positron emission tomography in cerebrovascular disorders. AB - The introduction of positron emission tomography (PET) as a powerful imaging modality has played a major role in the understanding of the pathophysiological bases for cerebrovascular disorders. PET is the only technique that allows measurement of regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen and glucose metabolism with detail and accuracy. Using PET, these physiological parameters can be measured to determine the extent of the disease from the early stages of cerebrovascular disorders to acute cerebral infarction. Significant hemodynamic and metabolic abnormalities are noted in chronic ischemia, but no structural changes are noted on anatomic images. PET studies have shown that in many patients in the early phases (10 to 12 hours) of clinically diagnosed acute stroke, a substantial area of ischemia exists, which, if untreated, will become irreversibly damaged. Similar to the results achieved in patients with acute myocardial infarction, appropriate intervention in patients with cerebrovascular disorders may significantly reduce the extent of injury to the brain. PET also has been useful in predicting functional recovery and monitoring the effects of various therapeutic approaches. Although functional imaging of the brain with single photon emission computed tomography can successfully be used in the investigation of several disorders of the brain, its role in cerebrovascular disorders is quite limited. PET is a unique modality that studies ischemic diseases of the brain, and it potentially could play a significant role in the management of patients with cerebrovascular disease. This will be further realized when aggressive approaches are used routinely in the future. PMID- 1439869 TI - The use of positron emission tomography in the clinical assessment of dementia. AB - A number of reasons can be cited for performing a test that identifies patients early in their course who have fatal and currently untreatable neurological disorders. At this stage of illness there is clinical ambiguity. The patient, family, and physician are typically faced with a battery of negative test results and an ambiguous clinical impression that can lead to periodic repetition of tests that involve cost, inconvenience, potential morbidity to the patient, and lack of definitive diagnosis. An accurate test would lead to the avoidance of these low-yield, repetitive, and costly evaluations. In addition, such studies can identify homogeneous groups of individuals with degenerative disorders leading to dementia who could be enrolled in experimental therapeutic programs. In these programs therapies could be monitored in an objective and noninvasive fashion using positron emission tomography (PET). The magnitude of the health problems resulting from the dementing illnesses is great in terms of medical practice, economics, and family hardship. The number of individuals with these disorders is predicted to increase dramatically in the future. The ability to provide an accurate diagnosis and more clear prognosis early in the disease course should diminish ambiguity for patients, families, and physicians. Ample evidence is cited in this article to show that PET has the ability to provide such information objectively and noninvasively. PMID- 1439870 TI - The use of positron emission tomography in the clinical assessment of epilepsy. AB - Positron emission tomography (PET) of local cerebral glucose utilization is highly sensitive in detecting epileptogenic regions that correspond to electrographic localization in patients with epilepsy. In medically refractory temporal lobe epilepsy for which surgical resection of the epileptogenic zone is a therapeutic option, the application of PET enables more than 50% of adults and older children to be successfully operated on without the necessity for chronic intracranial electrographic monitoring. In infants with intractable infantile spasms and various types of partial epilepsy, PET has uncovered focal areas of cortical dysplasia and other anatomic abnormalities, which, after resection, have resulted in cessation of seizures and developmental improvement. The distribution of PET abnormality is in excellent agreement with the extent of the epileptogenic zone as determined by intraoperative electrocorticography, thus avoiding the necessity for chronic intracranial electrographic monitoring in 90% of these infants. As a result of PET, the preoperative evaluation of intractable epilepsy in both adults and children has become less invasive and less costly. PMID- 1439871 TI - Neuropsychiatric disorders: investigation of schizophrenia and substance abuse. AB - Because neuropsychiatric disorders involve functional and neurochemical cerebral abnormalities, positron emission tomography (PET) is ideally suited for their investigation. The use of tracers to measure regional brain glucose metabolism and/or blood flow has allowed the evaluation of brain function in psychiatric patients. The use of radioligands to assess receptor concentration has enabled an evaluation of the extent to which specific neurotransmitter systems are involved in the pathogenesis of mental illness. This article reviews the application of PET technology to the understanding of schizophrenic disorders and substance abuse. PMID- 1439873 TI - Position emission tomography at the turn of the century: a perspective. AB - Nuclear medicine translates advances in molecular biology into the care of patients. In the future, diseases will be characterized at the molecular rather than the cellular level, often before detectable structural changes have occurred. Position emission tomography (PET) will play a major role in the study of intercellular communication by making it possible to characterize the actions of "molecules with messages." Diseases will be characterized by defects in intercellular communication. Treatment will be planned based on molecular abnormalities, and the response to treatment will be monitored with molecular probes. PET studies of the brain, heart, and cancer will be extended to all organs of the body. Pharmacology will be strongly influenced by PET because most drugs act by stimulating or blocking "recognition sites" on the surface of cells. In the next century, will single photon emission computed tomography (SPECT) makes PET unnecessary? The answer is no, because both PET and SPECT will have achieved a permanent role in medical practice; both make it possible to examine regional in vivo chemistry in human beings. Carbon-11 and fluorine-18 will continue to lead the way, but many drugs, and some body constituents such as proteins, can be radiolabeled with iodine-123 and technetium-99m. Today, PET is limited by the need to make one's own radiotracers. This is likely to change when regional radiopharmacies become widespread.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439872 TI - The role of positron emission tomography in oncology and other whole-body applications. AB - Imaging and quantifying biochemical and physiological processes with PET clearly has major potential significance for all organ systems and many disease states. Although the full utility and potential of emerging new applications of PET in organs other than the heart and brain must be demonstrated in basic and clinical research studies, the rapidly accumulating aggregate experience in oncology in particular, and in other organ systems and disease states as well, indicates that PET is now truly becoming a modality of both clinical and investigative use for the body as a whole as well as for specific organ systems. Whole-body PET FDG imaging (Fig 9) illustrates the potential of biochemical imaging to map the distribution of cancer throughout the body. With the growing list of radiopharmaceutical and quantitative techniques applicable to cancer studies with PET, this field will continue to realize significant growth. PMID- 1439874 TI - Mixed "hot" and "cold" lesions on bone scans. PMID- 1439875 TI - "Cold" lesions on indium-111 white blood cell scintigraphy. PMID- 1439876 TI - The "hot nose" sign in the cerebral radionuclide angiogram. PMID- 1439877 TI - Regulation of hepatic gene expression and development. AB - Tissue-specific expression in the hepatocyte appears to require the actions of multiple factors in specific combinations for each gene. The interactions between two or more positive-acting factors that raise transcription to optimal levels and those between positive and negative factors that enforce strict cell-specific transcription remain to be elucidated. However, recent progress in the identification and cloning of the genes for many of these factors will make it possible to begin to answer these important questions. PMID- 1439878 TI - Molecular pathogenesis of liver disease during persistent hepatitis B virus infection. PMID- 1439879 TI - Cellular and molecular mechanisms of hepatocarcinogenesis. AB - For colorectal carcinomas, the rate of tumor development is proportional to the fourth to sixth power of elapsed time, suggesting that four to six independent events are necessary. Although similar calculations have not been made for HBV associated HCCs, it is likely that this is also the case for HCCs, since individuals with persistent HBV infection do not usually develop HCC until they are 45 or greater years old. As evidence for specific genetic and epigenetic changes in HCCs accumulate, the important players in multistep hepatocarcinogenesis are becoming clearer. However, even though Myc family oncogenes are clearly implicated in woodchuck HCC, similar integrations have not been found in human HCCs. Therefore, although rodent and human systems have many similarities, we must realize that important differences may also exist. Regarding tumor suppressor genes, the evidence for p53 alterations in HCC is strong. A growing body of evidence suggests further that alterations in the retinoblastoma gene and one or more tumor suppressor genes on chromosome 11 are also involved in HCC. HBV integrations may certainly play a role in the generation of chromosome aberrations leading to loss of tumor suppressor alleles, since chromosomes 11 and 17 are the most common integration sites. Finally, the role of X proteins as participants in malignant transformation has been demonstrated for certain immortalized, nontransformed hepatocytes. Altered autocrine mechanisms of cell growth control, possibly involving IGF-II, are clearly implicated in HCC. Paracrine mechanisms for the control of hepatocyte growth and differentiated functions may also be altered as a result of the synthesis and secretion of a complex array of interleukins, HGF, and basic and acidic FGFs by cells in the inflammatory and cirrhotic lesions of precancerous livers. Whether the order of molecular changes in the hepatocyte is important for malignant progression is presently not clear. What is clear, however, is that hepatocarcinogenesis involves alterations in the concerted action of protooncogenes, growth factor, and tumor suppressor genes. How these factors interact will provide a more complete understanding of the mechanism or mechanisms of hepatic oncogenesis. PMID- 1439880 TI - New strategies for isolation of low abundance viral and host cDNAs: application to cloning of the hepatitis E virus and analysis of tissue-specific transcription. AB - The ability to clone viruses molecularly has led to dramatic advances in our understanding of this diverse group of agents at the molecular level. These insights are critical to the development of experimental strategies for the containment and control of the various viral pathogens that cause hepatitis in man. Knowledge of the genes and gene products have, for example, assisted in the design of expression systems that have been useful for the cell-free expression and production of viral constituents in the development of a subunit (recombinant) vaccine for HBV. Of particular advantage to the experimenter would be the ability to clone the virus directly from the infectious source without the need to resort to biologic amplification systems that require costly investments of money and manpower. This would obviate the need for the time-intensive development of a tissue culture propagation or the expensive cost of developing an animal model. The methods described here have applications to the discovery and isolation of low abundance transcripts from host (cellular) genes. These host encoded products may have important roles in virus replication and certainly by themselves constitute a growing area of study. The direct selection protocol has already proven its value in the isolation of novel (previously undescribed) gene sequences from complex cellular sources. The application of these methodologies should, at the single cell level, aid in the delineation of those important host encoded gene products that are critical for the efficient in vitro propagation of hepatotropic viruses. The identification of these low abundance cellular genes will elucidate the biologic interplay between host and obligate intracellular parasite (virus) and potentially lead to the development of new strategies for virus control that take into consideration the role of the cell as host. PMID- 1439881 TI - Molecular biology and genetics of alpha 1-antitrypsin deficiency. AB - The use of advanced recombinant DNA technology has provided an improved understanding of the human AAT deficiency phenotype by providing the amino acid sequence of several variant proteins and by allowing for the production of various cell and animal models to study the molecular and biochemical components of the retention, degradation, and accumulation of these variants in the hepatic ER. Human AAT deficiency will continue to serve as an excellent model for enhancing our current understanding of mechanisms utilized in regulating protein "traffic" in the ER and in elucidating the pathophysiologic components of AAT related liver disease. PMID- 1439882 TI - Structure, function, molecular genetics, and epidemiology of apolipoprotein B. PMID- 1439883 TI - Hepatocyte transplantation: development of new systems for liver repopulation and gene therapy. AB - Following recent advances in molecular and cell biology, development of hepatocyte transplantation has been considerably invigorated. To study the fate of hepatocytes transplanted into the liver, new strategies have included the use of endogenously marked transgenic hepatocytes. Release of peripherally quantifiable marker proteins by transgenic hepatocytes has provided noninvasive ways to determine hepatocyte engraftment and prolonged survival. Further characterization of intrasplenic hepatocyte transplantation has established this to be the most suitable method for targeting hepatocytes to the liver. Advances in gene cloning, retrovirology, and gene transfer technology have provided further tools for accomplishing gene therapy. Practical strategies for ex vivo gene therapy involving hepatocytes have been developed by exploiting these new technologies. The potential value of hepatocyte transplantation in acute hepatic failure has begun to be reexamined. Therefore, hepatocyte transplantation can be predicted to provide new ammunition for continuing our assault on untreatable disorders. Resolution of outstanding issues should accelerate this process. PMID- 1439884 TI - Strategies for gene therapy in the liver. PMID- 1439885 TI - End-stage liver disease in a 31-year-old man. AB - This is a case of decompensated chronic liver disease associated with FZ phenotype AAT deficiency. Histologic confirmation of the diagnosis was aided by immunostaining of the AAT globules. Liver transplantation was successful in reversing the disease process. PMID- 1439886 TI - Case of the season. Perforated benign gastric ulcer with perigastric abscess formation. PMID- 1439887 TI - Evaluation of cervical vertebral injuries. AB - The use of imaging studies on patients with suspected cervical vertebral injury should be restricted to those patients who fall into the high-risk category for injury. Once a decision is made to obtain radiographs, a minimum of five views is required to adequately rule in or rule out injury. Complex imaging studies such as CT, polydirectional tomography, and MRI may be performed to confirm the initial impression based on plain radiographic findings. The diagnosis of cervical injuries may be facilitated by following a logical pattern of analysis searching for abnormalities of alignment and anatomy, of bony integrity, of the cartilage or joint spaces, and of the soft tissues. This ABCS approach should simplify an intimidating subject and insure a confident radiological diagnosis. PMID- 1439888 TI - Thoracic spine trauma. AB - Thoracic spine fractures are most commonly flexion injuries resulting from vehicular accidents or falls. The initial evaluation of any multiple trauma victim should include AP and cross-table lateral radiographs of the thoracic spine. Conventional and computed axial tomography can add additional information regarding posterior element integrity and spinal canal encroachment. MRI can also be useful in that it directly images the effects of fractures on the spinal cord. PMID- 1439889 TI - Fractures of the lumbar spine. PMID- 1439890 TI - Magnetic resonance imaging in acute spinal injury. PMID- 1439891 TI - Trauma to the pelvic ring and acetabulum. PMID- 1439892 TI - MR imaging of skeletal metastases from medulloblastoma. AB - The findings of MR imaging in 3 patients with bone metastases from medulloblastoma are reported. The first patient showed focal lesions of low signal intensity on T1-weighted spin echo images at a time when bone scintigraphy was negative for metastases. This patient later developed extensive osteosclerotic lesions visible on plain films. The bone marrow of the second patient showed diffuse low signal intensity on T1-weighted images. After chemotherapy the signal intensity of the bone marrow increased which correlated with a return of normal hematopoietic tissue. A response to chemotherapy was also found on MR imaging and repeat bone marrow biopsies in a third patient. A consistent finding was a low signal intensity on pre-gadolinium images, but the pattern (focal or diffuse abnormal signal intensity) was different in each patient. To our knowledge, this is the first report on MR imaging findings in bone metastases from medulloblastoma. PMID- 1439893 TI - Alcoholism-associated spinal and femoral bone loss in abstinent male alcoholics, as measured by dual X-ray absorptiometry. AB - Although alcoholism is a known risk factor for osteoporosis, there are few published reports on alcoholism-associated bone loss. To study alcoholism associated bone loss, this study used a dual X-ray absorptiometry (DXA) densitometer to measure lumbar and femoral bone mineral density (BMD) in a previously little-studied population: 32 relatively healthy, nonhospitalized, Caucasian, alcoholic men with a period of abstinence longer than that previously studied (median abstinence 4.0 months, range 3 days-36 months). DXA is a new, highly precise densitometric method with many advantages over the methods used in previous studies. The subjects had statistically significant bone loss at three sites: lumbar spine, femoral neck, and Ward's triangle (multiple correction adjusted two-tailed P < 0.008). Compared to the mean BMD of sex-, age-, and race matched norms, the subjects' average femoral neck, Ward's triangle, and lumbar BMDs were, respectively, 0.56, 0.69, and 0.57 standard deviations (SDs) below the normative values. PMID- 1439895 TI - Computed tomography appearance of bone metastases of leiomyosarcoma. AB - Bone lesions in leiomyosarcoma are uncommon. When encountered, they are usually a late manifestation of disease seen in the setting of widespread systemic metastases. We present five cases of metastatic leiomyosarcoma, including one in which a bone lesion predated detection of a primary gastric leiomyosarcoma and one in which bone metastases signaled disease recurrence. Computed tomography in 14 of 16 osseous leiomyosarcomas demonstrated a lytic, non-expansile pattern. PMID- 1439894 TI - The hallux sesamoids revisited. AB - The hallux sesamoids are vulnerable to significant injury and weight-bearing stress in both the athlete and the nonathlete. Unfortunately, they are often dismissed as inconsequential accessory bones. The historical significance, embryology, anatomy, and physiology of the sesamoids and the salient features of both traumatic and nontraumatic pathologic conditions affecting these structures are presented. Because the sesamoids can be responsible for prolonged disabling foot pain and discomfort, it is important for both clinician and radiologist to pay attention to these bones and recognize the early signs of abnormality. PMID- 1439896 TI - Acronyms in bone densitometry. PMID- 1439897 TI - Shoulder impingement syndrome: impingement view and arthrography study based on 100 cases. AB - A prospective evaluation combining the shoulder impingement view and arthrography was made in patients presenting with chronic shoulder pain. Five hundred and twenty-three patients with chronic shoulder pain were X-rayed using conventional views and impingement views. One hundred of these patients (mean age 62 years) had subacromial bony spurs on the impingement view; these underwent arthrography. They were divided into two groups according to the degree of spur formation- whether or not the size of the spur exceeded one half of the acromial width as measured from the outer margin to the acromioclavicular joint. Of the 100 subacromial spurs demonstrated on the impingement view, only 18 were visible on the conventional view as assessed by an independent radiologist. Arthrography showed 35 cases of rotator cuff tear. The size of the bony spur was strongly associated with the incidence of rotator cuff tear (P < 0.02). PMID- 1439898 TI - Magnetic resonance imaging of Achilles tendon xanthomas in familial hypercholesterolemia. AB - The demonstration of tendon xanthomas is helpful in diagnosing heterozygous familial hypercholesterolemia, but in many patients lipid may accumulate without clinical abnormality being present. We investigated the possibility of detecting the lipid element with magnetic resonance (MR) imaging in seven patients with familial hypercholesterolemia and six controls. Although the mean relative signal intensities measured on long TR/TE spin echo sequences of the tendon were significantly higher in patients than in controls, the lack of such elevation does not rule out the presence of such lesions. In vitro measurements indicated that the signal intensity of triglycerides was quenched by cholesterolesters. The anatomic findings of MR imaging were compared with those of ultrasonography (US), showing excellent correlation in measurements between MR images and US [r(S) = 0.95 and 0.97 respectively]. MR imaging and US provide equal information on the anatomy of the Achilles tendon; as an abnormally increased signal intensity within the xanthoma on MRI was found in only a minority of our patients, the value of MRI in the demonstration of Achilles tendon xanthomas is limited when using conventional T1 and T2 spin echo sequences. PMID- 1439899 TI - MRI evaluation of amyloid myopathy. AB - Amyloid myopathy is a rare complication of primary amyloidosis. The magnetic resonance imaging (MRI) features of two patients with amyloid myopathy were studied. Slight prolongation of muscle T1 and T2 relaxation times was evident but the striking abnormality was marked reticulation of the subcutaneous fat. The clinical findings of indurated extremities far exceeds the minimal signal intensity alteration seen in the muscles. The MR appearance of amyloid myopathy differs from that of other neuromuscular conditions in the minimal changes found in muscle, but the striking abnormality seen in subcutaneous fat makes it distinct from many neuromuscular conditions. PMID- 1439900 TI - Case report 736: Retained surgical sponge (gossypiboma) with a foreign body reaction and remote and organizing hematoma. AB - This 50-year-old woman presented with progressive pain in the left thigh. Radiographs showed a 9 x 6 cm soft-tissue mass located at the lateral border of the left femur. Magnetic resonance (MR) examination showed an eccentric, nonhomogeneous, soft-tissue mass abutting the femur. The preoperative differential diagnosis was schwannoma, low-grade neurogenic tumor, large periosteal ganglion, or fibroma. At operation, the cut surface of the specimen had features of an organizing hematoma with recent remote hemorrhage and areas of fibrosis. Histopathological examination confirmed the presence of polarizable foreign body material in a background of foreign body reaction. The specimen represented a retained surgical sponge which had been present since the patient's surgery for a comminuted fracture 35 years earlier. Gossypiboma, or cotton balloma, is a term used to describe a mass within the body composed of cotton matrix. Radiopaque markers are now present on surgical sponges, and their appearances have been well documented. The gossypiboma, however, may still present a diagnostic problem if the marker is distorted by folding, twisting, or disintegration over a period of time. Without the radiopaque markers, retained sponges are difficult, if not impossible, to diagnose, as was the situation in this case. PMID- 1439901 TI - Case report 754: Xanthoma of the Achilles tendon. AB - The MRI features of bilateral xanthoma of the achilles tendon in type II hyperlipoproteinemia are reported. MRI has proved to be the best imaging modality available in assessing enlargement of the Achilles tendon. It demonstrates the heterogeneous signal on both T1- and T2-weighted images where the xanthomatous deposits are relatively higher in signal intensity than the tendon itself. MRI also has a potential value in the clinical assessment and therapeutic response of the xanthoma after operative intervention. PMID- 1439902 TI - Case report 755: Burkitt's lymphoma of the talus. PMID- 1439903 TI - Case report 756: Chronic multifocal osteomyelitis. AB - We report the case of a young boy referred to our Department of Nuclear Medicine under the suspicion of a malignant tumor. The leading clinical symptoms were pain in the joints and loss of weight and vitality. Radiographic findings were suggestive of osteogenic sarcoma, but bone scans showed multiple increased tracer depositions along the cortex of femur and tibia, and in the lower and upper jaw. The enrichment pattern was not typical for metastases, but more probably demonstrated the multiple foci of osteomyelitis. This assumption was confirmed by the histological findings, which were diagnosed as primary chronic osteomyelitis. This rare pediatric bone disorder has been described by Giedion et al. The etiology of the disease is unknown, and therapy is discussed controversely in literature. PMID- 1439904 TI - Case report 757: Giant cell tumor of rib. AB - A case of the rare occurrence of conventional GCT in a rib is presented. Due to its radiological aggressivity, the possibility of a MGCT was entertained clinically, and preoperative chemotherapy and radiation therapy were given. The literature on giant cell tumors of the ribs is reviewed, and their distinction from primary MGCT and other giant-cell-containing lesions is discussed. PMID- 1439905 TI - Contemporary health care and the colonial and neo-colonial experience: the case of the Dominican Republic. AB - This article traces the development of health care policies in the Dominican Republic from their colonial and neo-colonial roots to contemporary times. The Dominican case exemplifies the unique historical processes by which its health policies were created and maintained, and simultaneously, reflects the political and historical forces that shape the Caribbean as a whole. PMID- 1439906 TI - Transformations in maternity services in Jamaica. AB - Analysis of the current organization and delivery of maternity care in Jamaica profits not only from an assessment of recent health issues but from consideration of the development of maternity services over the past century. Historical analysis indicates that a critical element in public health policy has been the effort to encourage use of biomedical obstetrical care and to eliminate the lay midwife. However, while women increasingly patronize hospitals, the delivery of services has deteriorated, resulting in widespread client dissatisfaction. Economic contingencies have contributed to the decline in maternity services, but health personnel manifest the ideology prevalent throughout the colonial era equating social irresponsibility with health complications. The cultural construction of illegitimacy and maternity is shown to be a dimension of class relations having an impact on health policy throughout Jamaica's history. PMID- 1439907 TI - Social factors mediating social class differences in blood pressure in a Jamaican community. AB - Research on the factors mediating social class differences in blood pressure was carried out in a Jamaican community. It was found in a previous report that higher social class is related to lower blood pressure for females, while for males higher social class is related to higher blood pressure. These differences are examined in greater detail here, especially in terms of the historical context of the specific community studied, which is on the fringe of the Kingston urban area, and in terms of the continuing importance of a social class system established under colonial rule. In the current study it is shown that social class differences in blood pressure for males are mediated by perceptions of social support. Social class differences in blood pressure for females are mediated by perceptions of economic stress. It is suggested that specific patterns of the growth of the city, and the historically-based social class system, have resulted in the juxtaposition of lower and middle class Jamaicans within this community, who in turn are influenced by different factors affecting blood pressure. PMID- 1439908 TI - West Indian gender relations, family planning programs and fertility decline. AB - Nearly all West Indian islands initiated marked fertility declines sometime between 1960 and 1970. Family planning programs have not played an important role in these declines. Neither have other variables that conventional social theory tells us should promote reduced family sizes, like education and rising standards of living. The historical experience of Barbados and Antigua, which reached replacement-level fertility in the 1980s, suggests that West Indian fertility declines reflect structural changes in national economies that created job opportunities for women. Family planning programs need to be evaluated with reference to the distinctive health and human rights goals other than fertility transition that they can effectively reach. PMID- 1439909 TI - The effect of parental age, birth order and other variables on early childhood mortality: a Caribbean example. AB - The 4275 births to women of native ancestry that took place on the island of St Barthelemy, French West Indies between 1878 and 1970 were analyzed according to the sex of the child, the year of birth, maternal age, maternal parity, paternal age and the number of children the father already had to determine the effects of these variables on rates of perinatal death, death before age 1 and death before age 5. The year of birth, the number of children the father already had, and maternal parity influenced death before age 1 and death before age 5. The sex of the child also influenced the probability of dying in the first year of life but not the first 5 yr of life when the other variables were controlled. Perinatal deaths were influenced only by the sex of the child, but even this effect disappeared when the other variables were controlled. PMID- 1439910 TI - Family planning in St Vincent, West Indies: a population history perspective. AB - St Vincent's population history, first as a slave society, then, after Emancipation, as a migration-oriented society, has strongly influenced cultural attitudes towards sexuality and fertility. In contemporary St Vincent, sexual activity and procreative ability are highly valued and linked to social status for both men and women. This paper assesses historical and contemporary factors influencing population dynamics in St Vincent, West Indies, and Vincentians' reactions to programs developed to curb population growth. The efforts of private and government programs to introduce family planning and change pronatalist attitudes are evaluated for their cultural appropriateness. Shifting migration patterns and modernization are also affecting gender roles, the social and economic value of children, and the acceptability of contraception to contribute to recent fertility declines. PMID- 1439911 TI - Social inequities in cardiovascular disease risk factors in East and West Germany. AB - Social class related differences in prevalence of cardiovascular disease risk factors in Germany were investigated with special emphasis on comparisons between East and West Germany and on time trends. Databases for West Germany are the first and second National Health Survey (survey 1: N = 4794, survey 2: N = 5315), carried out in the framework of the German Cardiovascular Prevention Study, and for East Germany the first GDR-MONICA project (N = 6125). Different social class indices were applied to evaluate social inequities for hypertension, hypercholesterolemia, cigarette smoking, obesity and predicted cardiovascular disease mortality. As a main result, it was found that very similar patterns in the relation between social class characteristics and cardiovascular disease risk factor prevalence occurred for both parts of Germany. Social class gradients were strongest for obesity and weakest for hypercholesterolemia. Analysis of time trends for the period from 1984 to 1988 (for West Germany only) revealed an increase in social inequalities for hypertension in males and cigarette smoking in females. These findings point to the need to focus more on social disadvantaged segments in the population when community based health promotion and disease prevention programs are brought into action. PMID- 1439912 TI - An occupational health programme for adults and children in the carpet weaving industry, Mirzapur, India: a case study in the informal sector. AB - The Indo-Dutch Environmental and Sanitary Engineering Project under Ganga action Plan in Kanpur and Mirzapur is being executed within the framework of Indo-Dutch bilateral development cooperation. The project aims to integrate technological, social and health related improvements. It is expected that the development approach and methodology can be replicated in other urban settlements in India. The project is being supplemented by a training and institutional strengthening programme, which will facilitate the transfer of new technologies and improvements in operation and maintenance of these new technologies. One of the project's goals is to improve living conditions in the targeted areas by installing drinking water and drainage systems. A socio-economic unit (SEU) in the project supports these technical interventions by encouraging the community to participate in project activities. The Occupational Health Programme in Mirzapur was conceived by the SEU to improve the health and living conditions of child and adult weavers. At the start of the programme, 200 weavers and 60 non weaver workers from Mirzapur city, matched for age and socio-economic status, were interviewed and underwent a physical examination. The mean age of the weavers is 27 years, reflecting the relatively large percentage of child labour (13.5%). Illiteracy among them is 73%, whereas 14% have had only a primary education. 64.5% of the carpet weavers are Muslims and 35.6% are Hindus. 61% own a loom or work in a family owned loom shed. 95% of the weavers have a monthly income of less than 600 Rs. Complaints of a persistent cough and cough with expectoration, backache, the common cold and joint pains occurred more often in the weaver population than in the comparison group and have been identified as 'occupational hazards'. An intervention programme has been implemented based on the results of the occupational health survey. These interventions include awareness camps, installment of plexiglass tiles for light improvement in the loom sheds, training of community health volunteers and house-to-house health education. Another essential part of the programme is the provision of functional literacy classes for child and adult labourers in the carpet weaving industry. Occupational health as an entry point proved to be a successful approach in this segment of the informal sector, where child labour plays an important role. PMID- 1439913 TI - The costs of diabetes and its complications. AB - Diabetes mellitus is a disease with major long-term implications, not only for the health and well-being of affected individuals, but also for costs to the National Health Service. Treatment of the disease and its complications takes up 4-5% of total health care expenditure in the U.K. These costs are dominated by in patient care for the complications arising from diabetes. This paper presents a review of studies which have been carried out on the costs of diabetes and its complications. For such a chronic and potentially disabling disease with numerous complications it is surprising that costs have not been more extensively researched. A large amount of data are available about the implications of diabetes in terms of incidence and prevalence, but few costs have been collected, particularly indirect and marginal costs. Both insulin dependent (IDDM) and non insulin dependent (NIDDM) diabetic patients exhibit similar complications so that the cost of treatment may be comparable, but further studies are needed to establish this. In addition, few studies have included diabetes as a secondary diagnosis. The studies which are available have tended to focus on direct costs, for example, the costs of hospital care, consultations and drugs, because they are the easiest to measure. Fewer studies have included indirect costs, such as the effect of time lost from work, early retirement and premature death, because of the difficulties in assigning monetary values to these factors. The most important contributors to the costs of diabetes are those of treating complications such as eye and limb disease, heart disease, neuropathy and nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439914 TI - Depression and self-esteem: rapid screening for depression in black, low literacy, hospitalized tuberculosis patients. AB - One hundred black hospitalized tuberculosis (TB) patients (75 males and 25 females) were interviewed to ascertain levels of depression and self-esteem. The standard of literacy for 65% of the sample was such that they were unable to complete a self-report inventory. Reliability (internal consistency) was good for the 21-item Beck Depression Inventory (BDI: r = 0.79), the 13-item shortened BDI (ABDI: r = 0.76) and the Rosenberg Self-Esteem scale (RSE: r = 0.78). There was a significant positive relationship between the BDI and the ABDI (r = 0.92, P = 0.0001). The recommended ABDI cut-off scores established no depression for 32 patients, mild depression for 22 patients, moderate depression for 38 patients and severe depression for 8 patients. There were significant negative relationships between the BDI and the RSE (r = -0.54, P = 0.0001), and between the ABDI and the RSE (r = -0.56, P = 0.0001). Self-esteem scores dropped in accordance with category of depression, revealing that low self-esteem is a characteristic feature of depression. It was concluded that the ABDI was a reliable, rapid, initial screening device for depression in black persons with low literacy levels. PMID- 1439915 TI - Contributions of the proximate determinants to fertility change in Senegal. AB - The 1978 World Fertility Survey (WFS) and the 1986 Demographic and Health Survey (DHS) data are used to examine the relative contributions of three proximate determinants (nuptiality or marriage, contraception and post-partum infecundability) to fertility change in Senegal. The aim is to identify the important variables that is amenable for policy towards fertility reduction. Analysis shows that there are increases in the absolute measures of all three determinants. The magnitude of change is greatest in contraceptive use, moderate in marriage but least in duration of breast-feeding. However, the index of contraceptive use exerts the least impact on fertility reduction while that of post-partum infecundability makes the strongest impact on fertility. The impact of the nuptiality index on fertility change lies in-between contraception and breast-feeding. PMID- 1439916 TI - Going to extremes: the cultural context of stress, illness and coping in Antarctica. AB - The question of whether the concept of adaptation remains useful in medical anthropology is examined in the context of the human experience in Antarctica. This experience is characterized by prolonged isolation, confinement, and exposure to extreme environmental conditions. Men and women who winter-over at scientific research stations often exhibit a complex of psychophysiological symptoms in response to these stressors. However, this experience also appears to provide long-term health benefits. It is argued that the psychological symptoms are themselves part of the process of coping and do not necessarily represent an inability to adapt to the extreme environment. Coping is viewed as a process of negotiation leading to a compromise between individual and group needs. The cultural systems of Antarctic research stations are both a product of this negotiation and a set of normative and pragmatic rules regulating this process. Further, this process fosters the acquisition of new strategies or resources for coping with subsequent stressful experiences. PMID- 1439917 TI - Male and female morbidity in general practice: the nature of sex differences. AB - Outcomes from large scale health surveys suggest women's morbidity and medical care utilization to be higher than men's. Survey findings have often been questioned on methodological grounds, a main criticism being the subjective nature of the data on which the alleged sex differences are based. Moreover, health differences vary with the type of illness (behavior) that is assessed. Instead of asking subjects about their illness experiences, we performed analyses on data derived from a continuous registration of morbidity as presented in four general practices in the Netherlands. Information was obtained on physician diagnoses of 4723 male and 4963 female patients of all ages enlisted in the four practices from 1984 to 1988. To gain insight in the nature of sex differences, four diagnostic categories were distinguished (sex specific conditions, trauma, symptoms without disease, and prevention and diagnostics). Data on mean number of diagnoses, sex ratio's and proportions of overall morbidity are presented for separate age-groups. In addition, the contribution of each diagnostic category to overall female excess morbidity was computed, for age-groups. Results show that over 40% of the significantly higher overall female morbidity is accounted for by gynaecological and obstetrical diagnoses, and more than a quarter could be explained by prevention and diagnostics. In contrast with the often alleged female excess of 'vague' or psychosomatic symptoms, these accounted for less than 20% of the overall sex difference. PMID- 1439918 TI - Adolescence and health inequalities: extensions to Macintyre and West. AB - The paper investigates class based health inequalities in mid to late adolescence. Health status is assessed by means of three subjective self-report measures; evaluation of general health, psychological well-being and disability/long-standing illness. Using six measures of social class (three occupationally and three non-occupationally based) which derive from parental characteristics, no evidence for consistent class based differentials in health amongst adolescents is found. However, it is not concluded that class based health inequalities are absent at this stage of the life cycle. Instead, it is argued that the above measures of social class differentiate between young people on the basis of the socio-economic status of their parents. As such they fail to allow for the possibility that variations in the current social position of young people themselves may have important consequences for their health. Current social position is assessed in terms of economic activity status, occupation and educational attainment. Using these measures, class based health inequalities are indeed found. Extending the analysis further, the relationship between social class of origin, current social circumstances and self-assessed health status is investigated by considering inter-generational occupational mobility. Again, evidence for class based health inequalities is found. PMID- 1439919 TI - Health and nutrition effects of cash crop production in developing countries: a comparative analysis. AB - The paper presents results of a comparative analysis of the health and nutritional effects of cash crop production in 6 countries--The Gambia, Guatemala, Kenya, Malawi, the Philippines, and Rwanda. The 6 country case studies were conducted during the same time period and used a similar, although not identical, research protocol. Participation in cash crop schemes resulted in increases in household income. Short-term increases in household income did not result in a decrease in the incidence of illness in preschool-aged children nor in the total time that preschoolers were ill. Increases in household income did result in increases in the preschooler's energy consumption; however, the income/calorie consumption links, although significant, were weak. The household income gains did not have an immediate or large impact on preschooler nutritional status. While, in the longer term, increases in income may bring about improvements in preschooler health, in the short term, it appears that increases in income must be accompanied by improvements in the health environment in order to have a significant effect in reducing preschooler morbidity and improving child nutritional status. PMID- 1439920 TI - Psychometric investigation of a belief system: caregiving to the chronically ill parent. AB - This research draws on psychometric theory to assess open-ended items and develop reliable measures for investigation of caregiver ideology. Coding criteria used in a qualitative investigation of caregivers' beliefs about filial obligation and parental dependency were transformed into closed-end items and fielded with a large sample. Factor analysis confirmed the dimensions derived from the qualitative inquiry, but also showed that variability on the filial obligation dimension was greater than anticipated. Assessing familial caregivers' beliefs about filial obligation and parental dependency is useful, for these beliefs predict aspects of caregiver satisfaction and burden. Thus, beliefs about one's commitment to render care are not simply a norm divorced from behavior, but rather a cultural model with motivational force. PMID- 1439921 TI - On the seclusion of psychiatric patients. AB - The seclusion of psychiatric patients is viewed by some as a violation of basic human rights, by others as a necessity for the control of violence, and by still others as a therapeutic modality. The purpose of this paper is to synthesize the findings from the limited and descriptive research on this controversial practice. The major conclusions suggested by the findings are: (1) The reason cited for seclusion is more often agitation than violence, raising questions as to its necessity. The lack of relationship between the reason for seclusion and its duration indicates loose and arbitrary criteria and raises the question of bias. (2) The tendency to seclude on admission suggests failure to follow the legal stipulation that less restrictive measures be employed first. (3) Psychotic, involuntary and younger patients are at higher risk for seclusion than other patients. (4) Incidence and duration of seclusion differ widely across institutions indicating unnecessary and excessive use in some units. Differences may be better explained by hospital factors such as location, staff attitudes and treatment philosophy than by patient characteristics. (5) Systematic studies of the effectiveness of seclusion are lacking, as is research on events transpiring during seclusion. (6) Attitudes of patients and staff toward seclusion differ greatly. Patients' attitudes are generally negative, whereas staff members believe seclusion benefits patients and preserves the unit's smooth functioning. Changes in procedures are suggested to reduce the frequency of seclusion, and to make seclusion more rational, effective and humane. Research and clinical implications are discussed. PMID- 1439922 TI - A shamanic etiology of affliction from western Nepal. AB - As a central feature of every ceremony, Nepali shamans (jhakris) publicly recite lengthy oral texts, whose meticulous memorization constitutes the core of shamanic training. These texts include passages that explain the origins of diseases and afflictions, and provide elaborate instructions for their alleviation. Through a discursive analysis of key passages, I demonstrate that shamans possess a coherent etiology of affliction. These concepts are articulated as integrated parts of the treatments that shamans perform. Rather than attributing all afflictions to ambiguous other worldly causes, these shamanic etiologies identify precise sources and effects that cover a spectrum ranging from the purely physical to the purely metaphysical, intersecting the natural and supernatural worlds. Patients and the public are repeatedly instructed in this unambiguous system of affliction in every diagnostic and healing session, since these ceremonies always incorporate recitations of the relevant texts. Accessible to non-specialists, the system conveyed by these recitations acts to validate shamanic intervention as a significant and intelligible activity. Using their oral texts, shamans effectively reproduce worlds that require shamanic interventions. PMID- 1439923 TI - Alcohol consumption among male reindeer herders of Lappish and Finnish origin. AB - Ethnic differences in alcohol intake among male reindeer herders were studied, since historical evidence suggests that Lapps drink more than Finns and since the considerable freedom of the herding occupation may imply a high risk for alcohol problems. In 1988, 2001 men answered a mail questionnaire including questions on alcohol intake over the past 12 months. The mean alcohol intake was 22.3 g/day among the Lapps and 13.2g/day among the Finns (P less than 0.001). The percentage of heavy drinkers (20 g or more daily) was 33.9 among the Lapps and 19.1 among the Finns. The mean frequency of getting drunk was 35 occasions/year among both Lapps and Finns. An analysis of variance showed that alcohol intake was significantly related to age, marital status, region and being of Lappish origin, but not to being a full-time reindeer herder. A significant interaction between region and marital status was also detected. The Lappish reindeer herders drink more than their Finnish counterparts. The ethnic difference is not, however, very large when compared with the stereotypic view of the drunken Lapp. PMID- 1439924 TI - Infant mortality and illegitimacy. PMID- 1439925 TI - Why is health relatively poor on Sri Lanka's tea estates. PMID- 1439926 TI - Ethics are local: engaging cross-cultural variation in the ethics for clinical research. AB - Relatively little consideration has heretofore been given to the interaction between Western clinical research ethics and non-Western ethical expectations. How should any conflict that might arise when a biomedical investigator and a research subject come from different cultural settings and have different ethical expectations be addressed? Which ethics should govern such trans-cultural clinical research? The answers to these questions are of increasing importance because many countries of the developing world are presently sites of field testing of biomedical agents sponsored and administered by countries of the developed world, especially in the context of the AIDS pandemic. Drawing mainly on examples from Asian medical systems and settings, I elucidate four possible ethical models to guide the conduct of transcultural biomedical research. Two assume that research ethics are culturally relative and two assume that a unified, universalistic conceptualization of research ethics is possible. All four, however, are problematic and are to a large extent deficient. The cause of the deficiencies of these models lies, I argue, in the way that ethics are ordinarily conceived. The proper approach to ethical conflict recognizes that culture shapes (1) the content of ethical precepts, (2) the form of ethical precepts, and (3) the way ethical conflict is handled. Medical ethics may be viewed in cross-cultural perspective as a form of 'local knowledge', and any differences in such knowledge between cultures--since such differences will not conveniently disappear--must be engaged and negotiated. PMID- 1439927 TI - Culture, meaning and disability: injury prevention campaigns and the production of stigma. AB - The potential production of stigma through health promotion campaigns is a problem that has not received attention in the current literature on the sociology of health promotion. Cultural production studies can shed light onto the ways in which injury prevention campaigns, and public health campaigns more generally, may call for life-saving interventions at the social expense of people with disabilities or other stigmatized conditions. Questioned here are not only the presumed benefits of health promotion campaigns, but also our conventional understandings of 'health' and 'disability'. This paper examines the way in which cultural production studies can contribute to a theory of the production of stigma by public health professionals. One view of cultural production views culture as a reflection of economic relationships between the dominant and the dominated. A second approach emphasizes the 'reception' of cultural works, or how audiences experience culture. Third, cultural production is sometimes analyzed in terms of texts, or the content of cultural artifacts. Insight into the dilemmas of health promotion can be provided by analyzing health promotion strategies in terms of their production, reception, and content as cultural works. Focusing on the case study of injury control and disability rights, health promotion campaigns are seen as potentially contributing to the production of stigma for people who already possess the attributes targeted for prevention. This analysis moves toward a broader theoretical foundation with which to grasp the unintended, even harmful consequences of prevention strategies, and the shared and oppositional interests of people with stigmatized conditions, targeted audiences of prevention, and public health advocates. PMID- 1439928 TI - The relationship between consumption and worker productivity: nutrition and economic approaches. AB - That better fed, healthier individuals work harder may seem intuitively appealing but there is surprisingly little rigorous evidence to support the hypothesis. There are numerous problems in establishing a causal link between production and consumption due to difficulties in measuring the productivity of workers, misinterpretation of simple correlations between production and consumption, and jointly determined production and consumption variables. The extent to which research findings can be generalized to larger populations often is jeopardized by sample attrition and sample selection. It is the purpose of this article to explain how these empirical and experimental difficulties arise, their implications for research results, how they may be overcome, and to access what is known about the consumption-production relationship. The field of nutrition contributes understanding of the biological relationship between energy intake and energy expenditure, necessary measurement skills, and clinical evidence supporting the consumption-production hypothesis. Economists contribute understanding of the larger social context in which the biological relationship takes place and empirical techniques necessary to overcome measurement and data problems. PMID- 1439929 TI - On the edge: ward-rounds in a South African psychiatric emergency department. AB - Psychiatry, like other institutions in South Africa, is affected by issues of race. An examination of ward-rounds in a South African psychiatric emergency department, however, revealed that as important to an understanding of this unit is the recognition of the place of psychiatry in biomedicine. A key feature affecting staff in the unit was the fact of psychiatry's marginality relative to general medicine. Race was seldom and obliquely discussed, but played an important contributory role. Work towards the transformation of psychiatric care in a democratic South Africa must consider the institutional level as well as the more obvious question of racial inequality. PMID- 1439930 TI - Exploratory analysis of children's nutrition programs in Canada. AB - This survey examined the processes by which programs feeding hungry children in Canada are initiated, implemented and sustained. The responses of 32 operators of these programs were obtained by semi-structured telephone interviews and were analysed using qualitative research methods. Concerned citizens within the community and teachers were the major proponents for programs; their primary indicators of need were children's hunger-related behaviours. Programs generally provided the breakfast or lunch meal, were overseen by a board, and were operated by a mix of paid and volunteer staff. A lack of resources, problems with parents and the community, and managerial stresses were the main perceived barriers to program continuance. Programs run by communities generally had more need for resources, expressed lower confidence in their sustainability, and were less likely to cooperate with other groups than school-run programs. While some programs deliberately tried to avoid stigmatization, program operators did hold some prejudicial views about the communities they served and few programs could be considered empowering to users. PMID- 1439931 TI - Is users' knowledge about contraceptives adequate? A case study of Finnish IUD users. AB - Intrauterine contraceptive devices (IUDs) are popular: in Finland, in 1987, about 25% of women of childbearing age used them. We studied Finnish women's knowledge about contraindications for and side-effects of IUD use, with emphasis on current users. In December 1987-January 1988, a postal questionnaire was sent to a random sample of 1000 women of childbearing age, in Uusimaa province, which includes the capital, Helsinki. After three reminders, the response rate was 84%. We compared the answers of current and past users and nonusers of IUDs, and analyzed the associations between IUD use, education, age, and knowledge about side-effects. In contrast to the recommendations for use and information to be given to the contraceptive users, a substantial proportion of current IUD users assumed there are few limitations for IUD use. Some side-effects possibly leading to severe consequences were not considered to be connected with IUD use, not even by users. Although risk of infection was a quite well known fact, infertility was seldom associated with IUD use, and 22% of current IUD users did not associate ectopic pregnancy with IUDs. The results thus suggest that contraceptive counseling is not fully adequate and should receive more attention. PMID- 1439932 TI - Accounting for differences. Dutch training nurses and their views on migrant women. AB - Fifteen extended essays about working experiences with migrants, written by district nurses, were analyzed as part of a larger research project on the perception of child rearing practices in and family relations in migrant households. The nurses have all been working in child health centers and intended to improve their expertise in the position of migrant women and the background of child rearing practices in migrant households by means of a graduate project during their training as a district nurse or senior staff member. I was especially interested to learn how the huge amount of literature about the different cultural background of Turkish and Moroccan migrants was used by the nurses to elaborate ideas about the specific problems of migrant mothers and the possibilities of professional support in child rearing affairs. The analysis of the essays revealed that in most essays the concepts of 'ignorance', 'unequal gender relations' and 'isolation' are central in the construction of the category of Turkish and Moroccan mothers as a specific risk or problem group; and that 'cultural differences', 'transiency' and 'deficiency' play an important part in the nurses' 'explanatory model' of the risks and problems in these households. It is argued, that the meaning and interrelationship of the nurses' definitions and explanations of characteristics and problems in migrant households should be understood in the context of (1) the orientalist literature about the population of 'eastern' countries which is recommended in the professional trainings, (2) former and current perceptions of class differences in child rearing practices by professionals and (3) traditional ideas about the position and responsibilities of mothers which dominate in youth health care in the Netherlands.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439933 TI - Exploration of doctor and patient agendas in general practice consultations. AB - A method for the interactional analysis of doctor/patient consultations is described and applied to six naturally occurring general practice interviews by three raters. The method is reliable given sufficient training and satisfies the stringent criteria for any method of analysis for medical interviews proposed by Wasserman and Inui [1: Wasserman R.C. and Inui R.S. Med. Care 21, 279, 1983]. PMID- 1439934 TI - Influence of bed supply and health care organization on regional and local patterns of diabetes related hospitalization. AB - This paper undertakes both a macro- and micro-scale analysis of the influences exerted by the health care system on patterns of hospitalization. The health disorder of diabetes mellitus is used as the case study and the analyses are based on New Zealand data sets. The article first examines the extent to which both the supply and organization of primary and secondary health care affect rates of hospitalization. The macro-scale analysis investigates the applicability of Roemer's Law to regional variations in diabetes hospitalization. The organizational control of hospital utilization via doctor gatekeeping functions and interaction between health services are then examined at the local level. This analysis assumes a population based approach using the Canterbury Register of Insulin-treated diabetic persons as the study population. Diabetes discharge rates were found to be most highly correlated with hospital bed supply in 5 of the 8 years studied (1979-1986). Stepwise regression analysis indicated area rates of diabetes hospitalization were significantly influenced by resource factors even after controlling for differences in the socio-demographic characteristics of the area populations. This confirmed the presence of Roemer's Law at the aggregate level with rates of diabetes hospitalization appearing to have more to do with the availability of medical resources than to population needs. At the local level, hospital admission patterns were found to vary by general practitioner age, practice type found to vary by general practitioner age, practice type and diabetic caseload. Overall, insulin-treated diabetic patients most likely to be hospitalized were those in the care of young doctors new to general practice, and those who attended doctors who had small diabetic caseloads. Solo practitioners had the lowest rates of patient hospitalization. There were marked disparities in patient access to specialist diabetes education and clinical outpatient services by patient age, duration of diabetes and attendance on primary care. Overall, no significant differences were found in the propensity for hospitalization between users and non-users of these specialist services. This does not imply however, service ineffectiveness but rather is indicative of the complexity of the local diabetes care organization and the differing needs of the insulin-treated diabetic population within the community as a whole. PMID- 1439935 TI - Church-based obstetric care in a Yoruba community, Nigeria. AB - The analysis of data from available delivery registers in a Yoruba community, Nigeria suggests that about a half of recorded births between 1983 and 1990 were delivered in 'faith clinics' and not in a maternity centre. This paper reports on the mode of operation of these faith clinics in the town. It was observed that the faith clinics were under the control of mission-trained midwives all of whom claimed divine call as the reason for taking up the job. The midwives also listed prayer, fasting and guidance from the Holy Spirit as their main tools of trade. They offered no medicine to their clients and would not recommend any other treatment for them. Pregnant women that come for prenatal care are required to attend weekly prayer meetings for expectant mothers, take weekly baths in a particular river and maintain inward and outward cleanliness in their behaviour. The reasons for the relative success of these midwives in the town are discussed using a combination of economic, symbolic interactionist and pragmatic approaches. Recommendations on how best to tap their resourcefulness for a more effective health services delivery in the area include making them educators on and communicators of modern preventive health. PMID- 1439936 TI - Marital status and infant health outcomes. AB - Out-of-wedlock status has long been recognized as a demographic risk factor associated with infant mortality and low birthweight. However, the relationship between marital status and birth outcomes varies by maternal race and age. The negative impact of unmarried status is greatest for white women aged 20 and over. High infant mortality rates for married teen mothers challenge the assumption that marriage necessarily provides a protective environment for childbearing. Maternal and child health research and policy have been hindered by a deviance model of out-of-wedlock fertility, which is both biased and outdated. Inconsistencies in the effect of marital status indicate variations in both economic and social resources. Purely behavioral explanations for escalated risks to unmarried mothers are not justified by research findings. Alternative interpretations suggest the need for greater societal involvement in maternal health care created in part by changes in family structure. PMID- 1439937 TI - Psychosocial factors influencing non-urgent use of the emergency room: a review of the literature and recommendations for research and improved service delivery. AB - Despite dramatic increases in use of hospital emergency rooms (ERs) since the 1950s, an estimated 85% of ER visits are made for non-life-threatening reasons. Using a modified version of the Andersen and Newman model of health care utilization, this paper reviews the research literature on ER use to examine what is known about factors that influence three stages of the help-seeking process: (1) problem recognition; (2) the decision to seek help; (3) the decision to use the ER. While predisposing factors other than race are not generally significant, enabling factors such as income, insurance coverage, having a usual source of care, and geographic proximity affect use of the ER, both alone and in interaction with race and other factors. The most common reason for non-urgent ER use was 'other care not available'. In addition to the absence of primary care, non-urgent use of the ER is linked to need factors arising from socioeconomic stress, psychiatric co-morbidities, and a lack of social support. Recommendations for future studies include examining prospectively all 3 stages of decision making leading to ER use, and considering interactive effects among predictors. Implications for service delivery are discussed, including the need to re structure health care delivery systems to provide greater access to primary care and provide more attention to psychosocial aspects of patient care in clinical settings. PMID- 1439938 TI - Fertility differentials among the Ijo in southern Nigeria: does urban residence make a difference? AB - The paper tests some of the conflicting hypotheses regarding the effects of urban living and education on fertility by examining the fertility levels of women migrants--some educated, others not--to various urban centers in one Nigerian ethnic group. Of particular interest are the conditions under which the urban residents live and the concept of 'urban' is examined in this West African context. Research methodology consisted of a two-pronged approach and combined an intensive ethnographic study of the families in the rural home community and in one urban center with a demographic survey administered to a larger sample of the rural residents and urban migrants. Analysis indicates that the effect of education on fertility is more powerful than urban or rural residence. The importance of utilizing culturally appropriate categories in demographic research is discussed. PMID- 1439939 TI - 'New and improved' and other medical non sequiturs. PMID- 1439940 TI - Water sanitation practices on the Texas-Mexico border: implications for physicians on both sides. AB - With the epidemic of cholera in South and Central America and reports of cholera in the Northern Hemisphere in Mexico, increasing concern focuses on sanitation problems along the border between the United States and Mexico. It is feared that binationally shared water supplies are threatened or contaminated by sewage and other wastes. Although much anecdotal information exists, surprisingly few hard data are available in the United States (or in Mexico, for that matter) regarding water quality on the Mexican side of the border. This shortage of data is felt most acutely in the semiarid portions of the border, where water is extraordinarily scarce. In 1987, researchers at the University of Texas School of Public Health (UTSPH) began gathering data on the availability, accessibility, and bacteriologic and chemical safety of raw and finished drinking water in Mexico at its border with Texas. In view of their timely significance, we wish to share pertinent data. This particular study was carried out in Ciudad Juarez, a city of more than 1 million people, situated just across the Rio Grande from the Texas city of El Paso. The investigation was conducted at the invitation and with the assistance of municipal authorities of Cd. Juarez. As far as we know, this was the first time the water in Cd. Juarez had been tested for indicator fecal bacteria and other selected contaminants. PMID- 1439941 TI - Effect of aeromedical aircraft on care of trauma patients: evaluation using the Revised Trauma Score. AB - Rotor wing aircraft used in transport of the trauma victim have not been subject to objective means of evaluating their contribution to patient care. A retrospective evaluation of a Bell 206 L-1 and an Aerospatiale 365 N-1 using the Revised Trauma Score Triage (RTS) as an indicator of status in 98 patients transported from the scene of injury was conducted. Ground (GT), flight (FT), and total mission (TMT) times, as well as initial RTS, final RTS, and the difference between them (DRTS) were determined for all patients. Statistical analysis was done using two-way ANOVA. GT, FT, and TMT were significantly lower in patients transported by the 365 N-1. In more severely injured patients (RTS < or = 10), DRTS and final RTS were significantly higher in the 365 N-1; FT was significantly less. The contributions of various aeromedical aircraft to the care of the trauma victim may be assessed using objective indices of patient status. PMID- 1439942 TI - Gunshot wounds of the female breast: a risk for intra-abdominal injury. AB - We report the results of a clinical study of female patients sustaining gunshot wounds to a breast. Thirteen homicides were reviewed by the Fulton County Medical Examiner. A prospective series of patients treated by the Grady Memorial Hospital Trauma Service included eight additional cases. Ten (48%) of the combined series of 21 patients had significant intra-abdominal injury; of these, five (24%) had injuries confined to the abdomen as a result of a missile striking a breast. A wound pattern consisting of a superior breast entrance wound, an inferior breast exit wound, and an inframammary thoracoabdominal reentry wound was noted in five patients, four of whom had intra-abdominal injuries and three only intra abdominal injuries. Careful examination for this wound pattern should alert the clinician to the possibility of intra-abdominal injury. One should anticipate a 50% incidence of intra-abdominal injury in female patients sustaining gunshot wounds to a breast. PMID- 1439943 TI - Clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis: a prospective double-blind clinical trial. AB - Bacterial vaginosis is common among patients seen by gynecologists. Several types of therapy have been proposed. The purpose of this prospective, randomized, double-blind clinical trial was to examine the efficacy of clindamycin vaginal cream for the treatment of bacterial vaginosis. Sixty patients with symptoms of bacterial vaginosis were randomized into the study, and 46 completed the protocol. Twenty-three patients received 2% clindamycin vaginal cream (5 g applied intravaginally at bedtime for 7 days), with placebo oral tablets twice daily for 7 days. The other 23 patients received oral metronidazole tablets (500 mg twice a day for 7 days) and placebo vaginal cream (5 g intravaginally for 7 days). The cure rates for the two regimens were comparable. Twenty-two (97%) of the patients treated with clindamycin vaginal cream had improvement or cure at the first follow-up visit versus 19 (83%) of those taking metronidazole. There was no statistically significant difference between the two results. Side effects for both regimens were comparable. We conclude that 2% clindamycin vaginal cream offers similar efficacy and safety to standard oral metronidazole therapy for bacterial vaginosis. PMID- 1439944 TI - Wedge resection for bronchogenic carcinoma in high-risk patients. AB - At the Veterans Administration Medical Center in Washington, DC, 73 patients with bronchogenic carcinoma had pulmonary wedge resection from February 1967 to March 1988, with a 1.4% perioperative mortality and a 4.1% morbidity. Mean age of the patients was 63 years. Patients were considered poor risk with a mean Goldman index of 9 +/- 4 (class II), mean ASA physical status classification II, mean 1 second forced expiratory volume (FEV1) of 1.25 liters (42% predicted), ratio of FEV1 to forced vital capacity 30% predicted, and maximum voluntary ventilation 24% predicted. Staging of the bronchogenic carcinomas indicated 68% stage I, 15% stage II, and 17% stage III, and histology showed 41% epidermoid, 40% adenocarcinoma, 12% bronchoalveolar, 3% large cell, and 4% small cell type. For the 72 patients eligible for follow-up, data were available on 62 for a period ranging from 4 months to 15 years. Survival was 94% at 1 year, 55% at 3 years, 29% at 5 years, 5% at 10 years, and 2% at 15 years. Within 5 years, 21% of the patients had died of causes other than bronchogenic carcinoma. The rate of recurrence was 16%. Analysis by each stage of lung cancer showed local recurrence in 4% of patients with stage I disease, in 9% of those with stage II disease, and in 59% of those with stage III disease. We conclude that wedge resection provided acceptable surgical treatment in a group of high-risk surgical patients. PMID- 1439945 TI - Hereditary angioedema. AB - Hereditary angioedema is a rare disease resulting from a lack of functional C1 esterase inhibitor (C1 INH). Several genetic defects can cause decreased production of the protein or the synthesis of a biologically inactive form. A similar, acquired condition is occasionally seen, associated with malignancies or as an autoimmune process. Disease severity varies greatly among affected individuals. Most patients have cutaneous, laryngeal, or gastrointestinal edema, often in combinations. The symptoms may appear spontaneously or result from a stimulus, usually trauma. When clinical suspicion exists, measurement of the C4 level screens for the disease. An assay showing low serum C1 INH function confirms the diagnosis. When disease severity warrants, symptoms can be controlled with anabolic steroids or antifibrinolytics. Doses should be increased before symptom-provoking events. Emergencies are treated with plasma infusions, fluids, and pain control. Where available, C1 INH concentrate is the treatment of choice. Therapy can usually be monitored by control of symptoms. With appropriate therapy, most cases remain well controlled. PMID- 1439946 TI - Hypercholesterolemia: case finding in family practice. AB - The recommendations of the expert panel of the National Cholesterol Education Program (NCEP) have been endorsed by national medical organizations as standards for the detection and treatment of hypercholesterolemia, yet information on how these recommendations are being followed in primary care settings is limited. This study was done to determine how family physicians in four primary care clinics associated with a teaching hospital in a large southern city follow the NCEP guidelines. Of the total patient sample (N = 817), about 60% had at least one total serum cholesterol measurement. Patients in the younger age groups were less likely to have a cholesterol determination than older patients. Of those in the "self-pay" category only 33% had a cholesterol determination. Variability by clinic and provider type was also noted, with physician assistants showing the highest compliance with screening guidelines (75%), whereas only 43% of patients seen by family practice residents had a cholesterol measurement. Of patients who should have had a lipoprotein analysis, based on total serum cholesterol and risk factors, only 23% actually had a lipid profile. Our study and other similar ones point out that case finding varies considerably and that efforts to improve case finding need to continue. PMID- 1439947 TI - Reduction of caregiver stress by respite care: a pilot study. AB - The purpose of this study was to determine whether providing respite care to persons with Alzheimer's disease and other dementias decreased stress and mood disturbances in caregivers. Caregivers of persons receiving respite care (n = 7), and not receiving respite care (n = 8) were tested at entry into the study and at 5 weeks and 10 weeks, using the Profile of Mood States and the Relative's Stress Scale. Using repeated measures analysis of variance, a downward trend for study subjects and an upward trend for controls was found for Relative's Stress Scores. Similar trends were found on the Personal Distress Subscale of the Relative's Stress Scale. No difference occurred in rates of institutionalization between those receiving and not receiving day care. Our study suggests that respite care for demented persons living at home significantly reduces the stress among caregivers. PMID- 1439948 TI - Physicians' negative perception of sclerotherapy for venous disorders: review of a 7-year experience with modern sclerotherapy. AB - Sclerotherapy is the injection of a sclerosing substance directly into a varicosity or telangiectasia to cause damage, fibrosis, and eventual obliteration of the vessel. Although sclerotherapy has been shown to be effective with a low incidence of side effects, many physicians in the United States are unaware of the technique or view it in a negative way. To better define the extent of physician unfamiliarity or prejudice toward sclerotherapy, we surveyed a local medical community of gynecologists by anonymous written questionnaire. The results indicated that 82% of the responding physicians believed that their knowledge of sclerotherapy was insufficient to advise their patients, leaving patients to learn about sclerotherapy from mass media sources. Sclerotherapy was perceived as only slightly effective therapy for varicose veins and was thought to have a relatively high incidence of side effects. With recent improvements in the technique, our collaborative experience with 3000 patients receiving 50,000 injections over the past 5 years has shown that sclerotherapy is a safe procedure achieving outstanding cosmetic results with concomitant symptomatic relief of painful varicosities and telangiectases. Sclerotherapy, as practiced today, offers an effective, simple, and less costly alternative to surgical stripping for most varicose and telangiectatic veins. The survey data demonstrate the need to educate the American medical community about the technique and merits of modern sclerotherapy so that patients may be properly guided by their physicians to the best sources of care for their aching and unsightly leg veins. PMID- 1439949 TI - Nutritional concerns in the elderly. PMID- 1439950 TI - New-onset ascites in a young black woman. PMID- 1439951 TI - Pharmacologic treatment strategies for the depressed, poorly responsive patient. AB - Treatment-resistant depression implies a failure of response to an ample dose of antidepressant medicine, prescribed over a sufficient length of time. Assessing drug levels in the blood is often helpful in confirming the adequacy of antidepressant dosages. Augmentation of the pharmaceutical activity can be achieved by coadministration of lithium, triiodothyronine, and/or stimulants. Neuroleptics are also prescribed with the antidepressant when psychotic features accompany depression. Such enhancements to drug efficacy are usually an advantage over beginning a new medication because of shorter response time. When a decision is made to change the antidepressant, a structurally different option is more likely to induce a remission than a medication of similar configuration. Electroconvulsive therapy is the most powerful treatment choice for depressed patients, especially when suicidal or psychotic features are present. PMID- 1439952 TI - Geriatric assessment and general medical practice. PMID- 1439953 TI - Hypercalcemia due to hard water used for home hemodialysis. AB - We have described two patients from the same rural community in Georgia who had hypercalcemia during home hemodialysis. In the first patient the diagnosis was not considered until after the patient complained of the poor taste of her home tap water and of the white residue it left on her cooking utensils; other causes of hypercalcemia had been ruled out. The diagnosis was confirmed when samples of tap water that had passed through the in-line deionizer showed low to high calcium concentrations. Calcium concentrations were high after the deionizer filters had been in place for some time but within the acceptable guidelines for the type of filters used. The second patient, seen shortly after the first, had also received dialysis with hard water and also had hypercalcemia despite the use of an in-line deionizer. These cases suggest that dialysis-induced hypercalcemia can occur during home hemodialysis despite seemingly adequate pretreatment of the water source. PMID- 1439954 TI - Invasive pituitary adenoma coexisting with infiltrating temporal lobe glioma. AB - We have reported the case of a young man who had the uncommon coexistence of two relatively common intracranial tumors--a pituitary adenoma and a temporal lobe glioma. The pituitary adenoma invaded nerve bundles in the left cavernous sinus, but did not extend into the left temporal lobe, where an anatomically separate oligoastrocytoma was diagnosed at autopsy. Preoperative magnetic resonance imaging may assist in the diagnosis of this and similar uncommon conditions. PMID- 1439955 TI - Disseminated infection due to Mycobacterium chelonei. AB - We have presented a case of M chelonei subsp abscessus in an immunocompromised patient. The patient was given antimicrobial therapy, to which the organism appeared sensitive for 4 weeks, but he died because of other medical problems. Repeated negative blood cultures for mycobacteria after the initiation of therapy and a careful postmortem examination suggested that the antimicrobial therapy was effective. PMID- 1439956 TI - Metastatic adenocarcinoma of the prostate manifested as a sellar tumor. PMID- 1439957 TI - Double Meckel's diverticulum. AB - We have reported a case of double Meckel's diverticulum associated with volvulus of the small bowel. On extensive review of the literature, we found no other report of such a variant of Meckel's diverticulum. PMID- 1439958 TI - Recurrent meningitis associated with intragastric migration of a ventriculoperitoneal shunt catheter in a patient with normal-pressure hydrocephalus. AB - A 68-year-old man had ventriculoperitoneal shunt placement for normal-pressure hydrocephalus. Three and a half years later, he had repeated episodes of seizures and ophthalmoplegia. He eventually died of recurrent acute bacterial meningitis. At autopsy the distal segment of the shunt catheter was found inside the stomach, a condition believed to be responsible for the repeated attacks of bacterial meningitis. PMID- 1439959 TI - Hereditary angioedema associated with pancreatitis. AB - A 44-year-old woman with C1q esterase inhibitor deficiency was seen in consultation for recurrent right upper quadrant abdominal discomfort, nausea, and vomiting. Each of these episodes was accompanied by concomitant peripheral edema. Initial diagnostic efforts were fruitless. In time, intermittent elevations in amylase and lipase developed, and a diagnosis of relapsing pancreatitis was made. We contend that the patient's recurrent acute pancreatitis is associated with her hereditary angioedema. Possible pathogenesis could involve intermittent intrapancreatic edema with partial ductal obstruction or loss of inhibition on the kallikrein-kinin system. PMID- 1439960 TI - Deceptive liver histology delays diagnosis of cardiac ascites. AB - Cardiac ascites is a rare condition. Diagnosis is aided by liver histology, which characteristically shows diffuse hepatic congestion affecting the centrilobular region. In our case of refractory ascites due to constrictive pericarditis, diagnosis was delayed because centribular hepatic congestion was absent histologically. Contrary to numerous published reports, diffuse hepatic congestion is not uniformly present in cardiac ascites. Constrictive pericarditis is curable and should be considered in all cases of unexplained ascites, regardless of atypical hepatic histology. PMID- 1439961 TI - Magic lessons... PMID- 1439962 TI - Magic lessons: rated R. PMID- 1439963 TI - Contarini's condition: paradise regained. PMID- 1439965 TI - Endometriosis in teenagers. PMID- 1439964 TI - Multiple metastatic carcinomas along the course of axillobifemoral bypass graft: unusual complication of extra-anatomic bypass graft. PMID- 1439966 TI - From molecular medicine to public health. PMID- 1439967 TI - Immunity to the simian malarias in their natural hosts--some problems awaiting investigation. PMID- 1439968 TI - Appearance of adherent cells suppressive to erythropoiesis during an early stage of Plasmodium berghei infection in mice. AB - We examined the effect of adherent cells from bone marrow or spleen of mice infected with Plasmodium berghei on dyserythropoiesis. Significant reduction in number of erythroid progenitors (erythroid colony-forming units: CFU-E and erythroid burst-forming units: BFU-E) was observed in bone marrow as early as 1 day after P. berghei infection. When adherent cells were removed from bone marrow or spleen cells of infected mice, the number of CFU-E and BFU-E was clearly increased. Furthermore, addition of adherent cells from infected mice to nonadherent cells from normal mice inhibited erythroid colony formation significantly in a dose-dependent manner. These results suggest that the adherent cells obtained from bone marrow or spleen of mice in the early stage of P. berghei-infection have a suppressive effect on erythropoiesis. PMID- 1439969 TI - Human behavior in relation to selection of malaria treatment. AB - People in rural areas usually help themselves when malaria attacks by using a drug preparation under the name of "ya-chud" bought from the grocery in the village. The objective of this study was to determine the behavior towards malarial treatment of local inhabitants in two malarious areas in eastern Thailand. Groups of 271 and 131 local inhabitants in villages in Pong Nam Ron and Bo Thong Districts, respectively, aged more than 15 years were interviewed regarding health behavior in seeking care when they became ill with malaria. Forty-two percent of the population at Pong Nam Ron and fifteen percent at Bo Thong went to drug-stores or groceries when they developed minor illness, while 85.2% of the subjects interviewed at Bo Thong went to the local health center. However, when they became severely ill, treatment-seeking patterns were similar in the two study areas. Ninety-four percent of the subjects interviewed at Bo Thong and eighty-seven percent at Pong Nam Ron gave a history of having used ya chud in the past. On average, a set of ya-chud for malaria infection consists of 3-5 drugs: antimalarial drugs together with others such as analgesic antipyretics, steroids, anti-histamines, vitamins and antimicrobial agents (tetracycline). The price of one ya-chud varied from 3-9 baht. Such improperly use of antimalarial drugs in malarious areas can result in treatment failure and cause the development of drug resistance, which is a problem in the malaria control program in Thailand. PMID- 1439970 TI - Anti-tuberculosis programs in Thailand: a cost analysis. AB - The standard regimen, a combination of isoniazid and thiacetazone, which has been used for treatment of tuberculosis (TB) in Thailand for the past 20 years is inexpensive, but possesses a high degree of toxicity and requires 18-24 months of continuous treatment, resulting in poor compliance and a low success rate of treatment. The more efficacious short-course chemotherapy introduced into the National Tuberculosis Program in 1985 is limited by the high costs of drugs. However, the cost of providing care is not limited only to drug costs but also includes other services costs. The present study was undertaken to compare the total provider costs of 3 short-course regimens with that of the standard program in the treatment of newly diagnosed pulmonary TB. Data were collected at 4 zonal TB centers through out Thailand in 1987-1988. Analysis showed that the 3 short course regimens had lower costs than the standard regimen from the provider perspective. Among these 3 regimens that of isoniazid, rifampicin and pyrazinamide for 2 months, followed by isoniazid and rifampicin twice a week for 4 months had the lowest costs (Baht 1,499). Despite the lowest drug cost (B 431) of the standard regimen, the total provider costs were the highest (B 2,541) due to the highest routine service cost of B 2,066. Thus to determine the cost of a disease requires consideration of both drug costs and also other cost components. PMID- 1439971 TI - Effect of health education on community participation in control of dengue hemorrhagic fever in an urban area of Thailand. AB - Dengue hemorrhagic fever (DHF), a disease transmitted by Aedes mosquitos, remains a serious public health problem in Thailand. This paper describes the effect of health education efforts on a community-based DHF vector control program in the municipality of Mae Sot District, Tak Province, northern Thailand, from 1988 through 1990. In 1988, public health education on DHF and larval control through mass media, lectures and discussions reduced the Aedes Breteau index from 241 in March to 126 in June 1988. In 1989 and 1990, twice a year house-to-house visits by trained health workers were added to the health education campaigns. Aedes larval indices were decreased far more in the epidemic year of 1990 than in 1989. During this 3-year period, water-storage containers for drinking, washing, bathing and ant-traps were the primary sources of larval habitats, accounting for about 90% of the total breeding places. Reduction of Aedes larvae in these sources was due to various larval control measures. By August 1990 water containers for non-drinking purposes were the remaining important breeding places. The introduction of larvivorous fish may be an effective method of larval control for these containers. Most houses were supplied by public piped water system; however, a shortage of piped water for a period of time resulted in a significant increase in the number of water containers. An adequate water supply to the community should be provided continuously to prevent creation of new breeding places. Modifying behavioral practices to reduce domestic man-made water containers should be encouraged. PMID- 1439972 TI - A survey of knowledge, attitude and practice of the prevention of dengue hemorrhagic fever in an urban community of Thailand. AB - To evaluate the effect of a health education program on the prevention and control of dengue hemorrhagic fever (DHF) in the municipality of Mae Sot, Tak Province, a survey of adult residents, mainly housewives, was conducted in late April 1990 to assess their knowledge of DHF and practice of preventive methods. A total of 417 respondents from 417 households selected by a systematic-cluster sampling method were interviewed. More than 90% of them knew that the disease is transmitted by Aedes mosquitos and indicated water jars and water retention in the houses as the common breeding places. However, the other two common breeding places, ant-traps and cement baths, were less frequently mentioned. This finding was consistent with the greater proportion of respondents who reported no larval control methods for these two kinds of containers than for the others. Covering water containers was the most common practice to prevent mosquito breeding in drinking-water containers whereas addition of abate (temephos sand granules) or changing stored water frequently was commonly used for non-drinking water storage. Larval control for ant-traps was mainly accomplished by the addition of chemicals, including abate, salt, oil or detergent. Health education efforts in this area could induce the majority of respondents to accept themselves as responsible for the Aedes control program. Health education by health personnel played an important role in disseminating DHF information and prevention methods. Radio and television were the main effective mass media for public health education on DHF in this area. PMID- 1439973 TI - Intestinal parasitic infections in Likupang, North Sulawesi, Indonesia. AB - A parasitological survey was conducted on the inhabitants of 6 villages of Likupang, Minahasa Peninsula, North Sulawesi, Indonesia, in August 1991. A total of 419 fecal samples were examined by using direct smear, flotation, formalin ether concentration, Harada-Mori culture and agar-plate culture techniques. Five nematode and 7 protozoan parasites were detected, while trematode and cestode infection was not observed. Soil-transmitted nematode infections were predominant. Among the younger inhabitants aged less than 15, positive rates of Ascaris, Trichuris and hookworm infections were almost same, namely 45.7, 45.3 and 47.7%, respectively. Among the elder people aged 15 or more, positive rate of hookworm infection (89.4%) was much higher than Ascaris and Trichuris infections (19.3 and 26.1%, respectively). Village to village differences in parasite prevalence, probably due to socio-economic and sanitary-environmental differences were observed. Both Necator americanus and Ancylostoma duodenale were detected. The agar-plate culture was proved to be an efficient method for detection of hookworm as well as Strongyloides stercoralis. PMID- 1439974 TI - The effect of repeated chemotherapy on the prevalence and intensity of Ascaris lumbricoides and Trichuris trichiura infection. AB - The prevalence and intensity of intestinal nematode infections were assessed during 3 anthelminthic interventions in an urban community in Malaysia. The prevalence levels of Ascaris lumbricoides at Interventions 1, 2 and 3 were 30.6%, 18.9% and 15.5%, respectively and the mean intensities were 1.9, 0.75 and 0.81 worms per person. For Trichuris trichiura, the prevalence levels at Interventions 1, 2 and 3 were 46.9%, 21.6% and 15.7%, respectively. The mean intensities for T. trichiura at Interventions 1, 2 and 3 were 3.30, 0.92 and 0.07 worms per person. No gender-related prevalence and intensity were observed for the two geohelminths in this community. Prevalences and intensity had convex age profiles. Although repeated chemotherapeutic intervention reduced both prevalence and intensity levels, intensity was a more sensitive indicator than prevalence. The results indicate that age-targetting treatment at school children of 7-12 years of age would be an appropriate strategy for this community. PMID- 1439975 TI - Nutritional intervention in acute diarrhea: is a lactose-free formula essential? AB - A prospective study was done to determine the incidence of disaccharide intolerance among 3-36 month-old patients with acute watery diarrhea who were on breast feeding and/or lactose-containing formula. The effect of feeding intervention on the outcome was investigated. Significant disaccharide intolerance was defined as one with (1) biochemical derangements: stool pH < 6.0 (Riedel de Haen pH paper) and reducing substances > or = 0.5 mg% (Clinitest) on two consecutive determinations and (2) clinical evidence: high purging rate (> 10 gm/kg/hour) and reappearance of dehydration and/or weight loss while on a lactose containing milk. Seven of 92 patients (7.8%) had biochemical evidence of disaccharide malabsorption on admission. Subsequent monitoring of the study population showed absence of disaccharide intolerance. Despite a lactose containing formula, a significant (p < 0.05) reduction in stool output from the first to the second day (145.85 +/- 130.26 vs 115.43 +/- 95.65 g/kg admission weight) was noted. Likewise, weight gain from admission to discharge (4.56 +/- 3.44%) was observed. The mean total duration of illness (4.75 +/- 2.84 days) was well within the usual course of five to seven days. This study supports the current recommendation of continued breast feeding and/or use of lactose containing formula during acute watery diarrhea. PMID- 1439976 TI - Risk factors for hepatitis B carrier status among blood donors of the National Blood Center, Thai Red Cross Society. AB - A study of risk factors for hepatitis B carriers among voluntary blood donors of the National Blood Center, Thai Red Cross Society was carried out in a case control study design during January 1989 to June 1990. Cases were 876 blood donors whose blood identified HBsAg at time of recruitment and continued positive for more than 6 months. Controls were 1,750 blood donors whose blood was free from HBsAg who came for blood donation at the same period as the cases. The ratio of cases:controls = 1:2. Self-administered questionnaires were constructed and pretested before using both cases and controls. The study revealed that the risk factors for hepatitis B among voluntary blood donors were age of less than 30 years old; low socioeconomic status (family income of less than 8,000 Baht/month); single status, especially males; male occupations of students, monks, nongovernment workers compared with government officials; female occupations of laborers, students, nongovernment workers and government officials compared with housewives. Sharing of nail clippers, used blades and tooth brushes among family members are proved to be risk factors, especially among males. In addition, sharing of used blades in barber shops proved to be a risk among males while sharing of nail clippers in beauty salons, history of ear-piercing at department stores or history of caesarean section among females could not be shown to be risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439977 TI - Parasitological and histopathological studies on rhesus monkeys infected with Chinese mainland strain of Schistosoma japonicum. AB - Fifteen rhesus monkeys were infected by cutaneous exposure each with 200 or 300 cercariae of Schistosoma japonicum. The dynamic distribution of schistosomula in the skin showed that 77-90% of them were found in the connective tissue, while 10 23% migrated in the hair follicles and sebaceous glands at different time intervals after cercarial penetration. Dead schistosomula recovered from the skin varied from 8.7% to 28.7%. The average rate of adult worm recovery was 74.4% and 61.3% in the 6th and 15th weeks of infection, thereafter the rate decreased to 32.3% and 9.0% in the 19th and 42nd weeks, respectively. The mean length of mature pair-worms was 13.2 +/- 2.3 mm in male and 18.0 +/- 1.9 mm in female 6 weeks of worm age. Afterwards the body length of females and their sexual gland diminished markedly. The mean prepatent period was 35.0 +/- 0.6 days. The average size of mature eggs in the feces was 86.6 +/- 5.4 x 64.3 +/- 3.6 microns, and the peak of eggs passage in the feces occurred between 7th and 15th weeks after infection, later on the number of eggs markedly decreased. Skin reaction to the primary infection was slight. The pathological changes observed in liver were chiefly cellular infiltration of portal spaces and the lesions produced by egg granulomas. The mean volume of single-egg granulomas of the productive stage in liver was 22.7 +/- 10.5 mm3 x 10(-3). The most intensive damages in the gastro intestinal tract were observed in the large intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1439978 TI - Sensitivity of different isolates of Schistosoma japonicum from China to praziquantel. AB - Groups of C57BL inbred mice infected with each of the 4 different isolates, (Anhui, Hubei, Sichuan and Yunnan) of Schistosoma japonicum from the mainland of China were treated with praziquantel (PZQ) and the parasiticidal effects were compared. Worm reduction rate was recorded to assess systematically the sensitivity of 4 different isolates to PZQ in the mouse. Three dosage-levels of PZQ, ie 150, 230 and 310 mg/kg body weight in single doses were used. The worm development rates of control groups infected with schistosomes from Anhui, Hubei, Sichuan and Yunnan were 75.5, 81.8, 81.5, and 83.0%, respectively. At the dosage level of 150 mg/kg, the worm reduction rates for the 4 different isolates were 36.0, 33.9, 25.5 and 35.6%, respectively. At the dosage-level of 230 mg/kg, the rates were 47.1, 46.0, 38.1 and 47.7%, while at the dosage-level of 310 mg/kg, they were 59.3, 58.6, 50.8 and 61.7%, respectively. The results indicated that the worm reduction rate of the Sichuan isolate was lower than that of the other three isolates, however, the differences were not statistically significant, suggesting that schistosomes of Anhui, Hubei, Sichuan and Yunnan isolates bear resemblance in drug response. PMID- 1439979 TI - Thalassemia in the outpatient department of the Yangon Children's Hospital in Myanmar: basic hematological values of thalassemia traits. AB - The present study was conducted in the Outpatient Department (OPD) of Yangon Children's Hospital (YCH) during June to November 1990 to determine the hematological data of 133 Myanmar patients with thalassemia trait who were the parents of patients with known beta-thalassemia major or hemoglobin E (Hb E)/beta thalassemia. The mean values of hemoglobin (Hb) concentration, packed cell volume (PCV), mean cell hemoglobin (MCH) and mean cell volume (MCV) were significantly lower than normal controls but the mean cell hemoglobin concentration (MCHC) was the same as controls. Increased osmotic resistance tested in 0.36% buffered saline was detected in 81-97% of cases depending on the cut-off point. High levels of Hb A2 (> 3.5%) were found in 93% of cases whereas Hb F was increased (> 0.8%) only in 23% of cases. Although the mean red cell count (RBC) was significantly higher than normal, only 79% of thalassemia traits were detected if the RBC count of > 5.0 x 10(12)/1 was taken as the discrimination limit. Other discrimination functions such as MCH/RBC, MCV/RBC, (MCV)2 x MCH x 0.01 and MCV (RBC/10(12)/1)-(5 x Hb) - 3.4 or - 8.4 were tested for their utility in diagnosing thalassemia traits. All of them were found not to be superior to each of the simple tests (MCV, MCH, Hb A2 or osmotic fragility) in diagnosing thalassemia traits. The one tube osmotic fragility test is a the suitable test to be used in future thalassemia screening programs in Myanmar. PMID- 1439980 TI - Thalassemia in the outpatient department of the Yangon Children's Hospital in Myanmar: knowledge, attitudes and practice in relation to thalassemia. AB - A maternal knowledge, attitudes and practice (KAP) study concerning the nature and prevention of thalassemia was carried out at the Yangon Children's Hospital in Myanmar. The KAP information was collected using a pretested schedule. Only 18 to 28% of the mothers knew at least one of the statements: thalassemia is a genetic disorder; both parents of thalassemic children carry abnormal genes; there is a 25% chance of recurrence in each subsequent pregnancy. Eighty-two per cent of the respondents decided not to have a further pregnancy for fear of recurrence and of these 62% were currently practising contraception. Oral contraception was the most commonly used method (56%). The median scores as well as the percent responses in favor of the three attitude scales relating to limiting thalassemic children, prenatal diagnosis and termination of pregnancy were high. Although there is a need to increase the community awareness of thalassemia in Myanmar, there is a possibility that prenatal diagnosis and pregnancy termination will be accepted for the prevention of thalassemia. PMID- 1439981 TI - Thalassemia in the outpatient department of the Yangon Children's Hospital in Myanmar: cost analysis of the day-care-room services for thalassemia. AB - A cost analysis study for the fiscal year 1989-1990 was conducted in the day care room (DCR) for thalassemia patients at the Yangon Children's Hospital in Myanmar to provide a basis for future cost-effectiveness, cost-benefit and efficiency analyses. Two types of costs, hospital costs and costs borne by the patients' families were studied by reviewing hospital records and by interviewing family members of patients. Of the total cost of DCR services for thalassemia 74 to 75% was contributed by material costs most of which were for imported items. The cost of each transfusion visit and the annual cost per patient were Kyats 166.5 to 173.3 and Kyats 1,108.6 to 1,208.7, respectively. The median cost (range) per treatment visit and the averaged annual median cost (range) borne by the patients' families were Kyats 21 (0-302) and Kyats 107 (0-1,509), respectively. PMID- 1439982 TI - Are the endemic motor neuron diseases of Guam really disappearing? AB - Death certificates were reviewed to observe trends in the number of persons on Guam reported to have chronic degenerative motor neuron diseases (amyotrophic lateral sclerosis, parkinsonism-dementia or Parkinson's disease) at the time of death. Additional data, including age and race of the deceased and the name of the certifying physician were also collected. The number of persons having been diagnosed with amyotrophic lateral sclerosis is apparently decreasing while their mean age is increasing suggesting that the etiologic agents or factors causing this disease are less prevalent on Guam today than they have been in the past. Trends with regard to parkinsonism-dementia and Parkinson's disease are less clear. PMID- 1439983 TI - Ivermectin and diethylcarbamazine trials in leaf monkeys (Presbytis cristatus) infected with Wuchereria kalimantani. AB - Clinical trials of Ivermectin in single oral doses of 200, 400, and 1,000 mg/kg body weight or in multiple doses of 200 mg/kg body weight for 5 consecutive days were performed in leaf monkeys (Presbytis cristatus) infected with Wuchereria kalimantani. Optimal microfilaricidal effect occurred at 200 mg/kg body weight. The drug was less effective than diethylcarbamazine in this animal model for human filariasis but had no adverse effects. PMID- 1439984 TI - Etiology of acute severe lower respiratory tract infection in hospital-based patients. AB - Acute respiratory infections are common childhood illnesses. Most are mild and self-limiting. Five percent are lower respiratory tract diseases and are potentially serious. A prospective study was conducted to ascertain the etiology of community-acquired severe lower respiratory tract infections (LRTI) in hospital based patients. Mycoplasma was the most frequently identified agent (33%). This was followed by viruses (28%) and bacteria (15%). Twenty-four percent of children had no identified causative agent. PMID- 1439985 TI - Immunological activities of monoclonal IgG1 antibody against Trypanosoma gambiense. AB - The present paper deals with the immune reaction between a monoclonal IgG1 antibody and Trypanosoma gambiense. The aggregation of trypanosomes, immune adherence to macrophages and protection against infection are associated with the antibody. IgG1-mediated clumping of trypanosomes is readily dissociated by the addition of complement. Dissociation of the clumped trypanosomes in the equivalence area released approximately fifty percent of previously bound surface antigens. These antigens were capable of binding again to new IgG1 antibody. Complement deposition rendered bivalent IgG1 antibody in the immune complex functionally univalent. Such an event in the presence of complement is of great advantage to the infected host in killing pathogens in vivo, as it allows more antibodies to attach to surface antigens and subsequently to initiate complement activity. PMID- 1439986 TI - Course of antibody production by the DIG-ELISA method in neonatally infected and juvenile infected rats after primary infection with Breinlia booliati (Filarioidea: Onchocercidae). AB - The course of antibody production in Wistar neonatal and juvenile rats after primary infection with Breinlia booliati was studied by the DIG-ELISA technique using filter papers impregnated with capillary blood drawn from the infected rat tails at 7, 14, 28, 60 and 90 days post infection. Sera of neonatally infected rats did not react with adult worm antigen until day 7 and the titers of antibody remained at very low levels for the next 7 days. There was little tendency to eliminate the filarial larvae during this time. The antibody levels then rose rapidly throughout the next fortnight and increased to a maximum at day 60 after which the titer leveled out at a constant high value until early patency at day 90. On the other hand, antibodies could be detected in sera of juvenile infected rats as early as day 7 and the levels of antibody rose markedly to a maximum at day 28. During the period from day 60 to day 90 at early patency, the antibodies declined gradually to lower levels. The humoral immune responses of 42 neonatally infected rats and 53 juvenile infected rats of 3 strains (Lewis, Wistar and Sprague Dawley) were tested against soluble B. booliati antigens from both female (1:50) and male (1:10) worm extracts by the DIG-ELISA method. Antibodies were detected in sera from all the microfilaremic and amicrofilaremic rats belonging to neonatally and juvenile infected groups. Sera of clean neonatal rats did not give a positive reaction zone. PMID- 1439987 TI - Microbial flora in gut of Culex quinquefasciatus breeding in cess pits. AB - The number and types of microorganisms in the gut of Culex quinquefasciatus larvae varied considerably from one site of collection to another. Larval gut, in general, contained enormous number of bacteria, a few fungi and negligible number of actinomycetes which belonged to 15 bacterial, 6 fungal and 4 actinomycete genera, respectively. Bacillus sp., Staphylococcus sp. and Pseudomonas sp. among bacteria, Aspergillus among fungi and Streptomyces sp. among actinomycetes were frequently encountered. Escherichia, Proteus, Aspergillus and Streptomyces were the most abundant genera. Isolates of Bacillus, Pseudomonas, Shigella and Staphylococcus caused 100% mortality during the early instar of larval development. None of the fungal isolates effected 100% mortality while Nocardiopsis sp. among actinomycetes gave 100% mortality. One of the Escherichia isolate suppressed the adult emergence completely while 27 others, belonging to most of the genera found, suppressed significantly. Isolates of Aspergillus, Alternaria and Streptomyces inhibited the emergence of adults completely. PMID- 1439988 TI - Malacological survey in the Sirikit reservoir, the largest earthfilled dam in Thailand. AB - Ten species of freshwater molluscs were found in a malacological survey in the Sirikit reservoir in 1985. Among these species, Tricula aperta or Neotricula aperta, intermediate host of human schistosomes, Bithynia (Digoniostoma) siamensis goniomphalos and B. (D.) funiculata, the first intermediate host of Opisthorchis viverrini were not found. It is revealed that most of the habitats in the Sirikit reservoir are not suitable for the survival and colonization of molluscs. Thus few species of edible molluscs in small numbers were found, except for Limnoperna siamensis, which were found in large numbers in the reservoir. Although it is not a medically important species, their attaching in large colonies may reduce the volume of water flowing into the power tunnels and obstruct small pipe lines in the dam area. So it is recommended to further study the life cycle of L. siamensis and to determine suitable molluscicides or biological agents to be used in controlling them. PMID- 1439989 TI - Mammonogamus (Syngamus) laryngeus infection: a first case report in Thailand. PMID- 1439990 TI - An unusual case of listeria meningitis. PMID- 1439991 TI - Albendazole treatment of neurocysticercosis. PMID- 1439992 TI - Control of Opisthorchis viverrini cercariae using the copepod Mesocyclops leuckarti. PMID- 1439994 TI - Pathways into sheltered employment. AB - Work ranks high in the rehabilitation of the mentally ill. Currently sheltered employment is often the only alternative to unemployment. We present a sample of 121 patients working at various facilities for vocational rehabilitation. All of these patients are chronically mentally ill, 77% of them suffering from schizophrenic disorders. With respect to their vocational backgrounds, they represent four groups that had come to the sheltered workplace by various means. One group of young patients had never had gainful employment, a second group had found jobs on the open labour market after onset of their illness, and a third group had been employed both before and after the onset of mental illness. The largest group, however, comprised those patients who had dropped out of normal working life immediately on onset of their illness to work in sheltered employment. The rate of isolation from working life was found to be influenced neither by professional qualification nor by the extent of vocational integration prior to the onset of mental illness. We discuss the consequences of the subjective experience of patients and the opportunities and problems presented in practice by vocational rehabilitation of the chronically mentally ill. A 5-year prospective study on the course of vocational rehabilitation is being designed by our group to provide further information on this subject. PMID- 1439993 TI - Changes in the prevalence of symptoms of depression and depression across Greece. AB - This paper reports on the regional prevalence of symptoms of depression and clinical depression (current major depressive episodes) in Greece in the years 1978 and 1984. Prevalence rates were estimated from two extensive, nationwide cross-sectional home surveys on psychosocial issues and health, carried out in four geographical areas: the Greater Athens area, the Greater Thessaloniki area, the rest of the urban areas and rural areas. The methodology used, the sampling procedure and the screening instrument (The Center for Epidemiologic Studies Depression Scale) were the same in both surveys. Within the 6-year period a substantial increase in the prevalence of symptoms of depression in all geographic areas was observed, with the Athenian respondents expressing a higher number of symptoms of depression than their counterparts from the other areas. The prevalence of current major depressive episodes, according to specific criteria matched with criteria from the DSM III R, was increased in 1984 in Athens and in the rural areas only. We suggest that economic instability between 1978 and 1984 probably contributed to the changes in the rates of depressive disorders. PMID- 1439995 TI - Psychiatric diagnostic profiles in hospitalized adolescent and adult Navajo Indians. AB - Diagnostic profiles of 400 adolescent and 1159 adult Navajo Indians consecutively admitted to a psychiatric unit between 1980 and 1989 are presented in this paper. The major discharge diagnoses for adolescents were as follows: adjustment reaction, mixed, and depression, not otherwise specified (NOS), with females accounting for two-thirds of either diagnosis; schizophrenia, with males accounting for 68% of all diagnoses, and personality disorder, NOS, with no gender differences. The four major discharge diagnoses for adults were schizophrenia and depression, NOS, in which there were no gender differences; alcohol withdrawal, syndrome, in which males accounted for 76% of those discharged; and adjustment reaction, mixed, in which females constituted 60% of those discharged. Over the 10-year period, there was a decrease in adult and an increase in adolescent admissions. During the last 2 years (1988 and 1989) adolescents accounted for almost 30% of all admissions compared with 14% during the first 2 years (1981 and 1982). PMID- 1439997 TI - Psychosis in Asian immigrants from the Indian sub-continent: preliminary findings from a follow-up study including a survey of general practitioners. AB - The paper presents preliminary findings from a follow-up study of 86 first generation immigrants to the United Kingdom from the Indian sub-continent, and a matched indigenous English-born control group. All subjects had originally been seen at the Bethlem Royal and Maudsley Hospitals and had been diagnosed as suffering from a functional psychosis. Attempts to locate the patients 5-20 years later revealed that a significantly higher proportion of the immigrant group could not be traced to a general practitioner within the United Kingdom, or otherwise accounted for. Possible explanations for this finding are advanced; the fact itself has important implications for those concerned with the provision of care and services for mentally ill immigrants in this country. PMID- 1439996 TI - DSM-III mental disorders in general medical sector: a follow-up and incidence study over a two-year period. AB - In three general medical settings (general practice, hospital medical wards and emergency rooms) about 20% of the adult attenders had a DSM-III mental disorder, mainly in the area of affective and anxious disorders. Some of these disorders were quite severe. Of those cases reassessed 1 year and 2 years after the first interview, less than a quarter reached a "no-diagnosis status". The chronicity of most cases dependent on the interplay not only of either relapse or duration of the main disorder but also of comorbidity and incidence of new disorders. A high incidence of more transient disorders in subjects who were well at first assessment was also found. PMID- 1439998 TI - Prodromal symptoms in manic depressive psychosis. AB - Twenty patients suffering from manic depressive psychosis were interviewed about the prodromes to both manic and depressive episodes. These prodromal periods were compared with a recent control period during which the patient was in remission. It was possible for 85% of patients to identify a depressive prodrome and 75% a manic prodrome. Prodromal periods were characterised by a significant increase in the number and magnitude of symptoms compared with those present during remission. The mean duration of manic prodromes was slightly longer than that of depressive prodromes (28.9 days and 18.8 days respectively). The majority of patients could identify a time sequence to the retainment of insight during their prodromes and could also identify idiosyncratic symptoms. PMID- 1439999 TI - Cross-national differences in the frequency and outcome of schizophrenia: a comparison of five hypotheses. AB - Measures of morbid risk for schizophrenia derived from the WHO Determinants of Outcome of Severe Mental Disorders Study showed large correlations with the following: an occupational index, a measure of urbanicity, geographical and climatic variables, a dietary measure, and the infant mortality rate. The same variables were also correlated with a measure of outcome derived from the International Pilot Study of Schizophrenia. Nearly all of the correlations were significant. The postulated "explanatory" variables were themselves highly intercorrelated. PMID- 1440000 TI - Effect of cervical spine motion on the neuroforaminal dimensions of human cervical spine. AB - A nerve root impingement within a stenotic neuroforamen is a common sequela of cervical degenerative arthritis and herniated nucleus pulposus. Understanding of the effects of cervical position on foraminal size is important in the assessment of pathology and injury, for selection of a provocative maneuver to elicit symptoms and in selecting a position of immobilization for the management of nerve root impingement syndrome. This biomechanical study of human cadaver cervical spines reports the measured variations in the sizes of neuroforamina as a function of cervical positioning. Five fresh frozen adult human cadaver cervical spines (C2-T1) were tested with combinations of flexion-extension and rotational position. Ten pounds of axial load was applied to simulate a normal loading of a cervical spine. The foramina of C5, C6, and C7 were directly measured using a set of finely graded circular probes. Compared to the foraminal diameter at the neutral position, there were statistically significant reductions in the foramen diameter of 10% and 13%, at 20 degrees and 30 degrees of extension respectively (P < 0.01). Conversely, in flexion, there were statistically significant increase of 8% and 10% at 20 degrees and 30 degrees of flexion respectively (P < 0.01). Though there was a reduction in the foraminal size with ipsilateral 20 degrees rotation, and an increase with contralateral 20 degrees rotation, these changes were not significantly different from the mean of the control. Combinations of flexion or extension position with axial rotation did not significantly change the foraminal size compared to the respective sagittal position with no axial rotation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440001 TI - Repair of symptomatic pseudoarthrosis of anterior cervical fusion. Posterior versus anterior repair. AB - Thirty-four patients with symptomatic pseudarthrosis of anterior cervical fusion were treated. There were 16 men and 18 women. Eighteen patients had pseudarthrosis at 1 level; 14 at 2 levels; and 2 at 3 levels, with C5-6 and C6-7 levels most commonly involved. Anterior repair of pseudarthrosis was done in 17 patients, which resulted in 76% radiologic fusion. Of 17 patients repaired posteriorly, 94% achieved radiologic fusion. Average follow-up was 60 months, with a minimum of 24 months. "Excellent" or "Good" results were achieved in 59% of anterior repair and 88% of posterior fusion group. This study demonstrates that posterior cervical fusion is the more effective method for repairing symptomatic pseudarthrosis of anterior cervical fusion. PMID- 1440002 TI - Electromyographic detection of paraspinal muscle metastasis. Correlation with magnetic resonance imaging. AB - Electromyographic (EMG) examination demonstrating marked segmental compromise of the posterior primary ramus distal to the spinal root with relative sparing of the anterior ramus may be the earliest objective evidence of paraspinal muscle metastasis. Antecedent studies are often initially normal, failing to disclose the underlying cause of back pain. Although paraspinal muscle metastasis has been histopathologically demonstrated at postmortem, attempts to image the suspected malignancy with computed tomography have been unsuccessful because the tumor in muscle remains isodense. This study reports the use of magnetic resonance imaging (MRI) to substantiate the existence of EMG-suspected paraspinal muscle metastasis. An EMG pattern of segmental posterior primary ramus denervation is not pathognomonic of metastasis. A confirmatory MRI, however, does permit earlier treatment with palliative radiation therapy. PMID- 1440003 TI - Effects of distraction on physiologic integrity of the spinal cord, spinal cord blood flow, and clinical status. AB - The authors determined the effects of distraction of the spine on physiologic integrity of the spinal cord using neurogenic motor evoked potentials (NMEPs), somatosensory evoked potentials (SEPs), spinal cord blood flow measurements, and clinical status in nine hogs. Spinal cord blood flow was measured after each level of distraction using the hydrogen washout technique. The results indicated that blood flow of at least 65% of baseline was required to maintain physiologic integrity of the spinal cord, and that a decrease of blood flow to 12% of baseline was associated with paraplegia. Neurogenic motor evoked potentials always correlated with the animal's postsurgical clinical status, whereas the SEP was falsely negative in one animal. PMID- 1440004 TI - Choosing fusion levels in progressive thoracic idiopathic scoliosis. AB - The selection of fusion levels in thoracic idiopathic scoliosis was subjected to multicenter retrospective review to test the validity of the classification system and recommendations of King et al. The 253 patients reviewed were treated by posterior fusion and Harrington instrumentation. Bending films were of little help in selecting fusion levels. Standing radiographs alone were usually adequate. King Type II curves may yield better lumbar correction if the lumbar curve is partially included in the fusion. Type IV curves may be safely fused one level proximal to the stable vertebrae. PMID- 1440005 TI - Chiba Spinal System in the operative management of scoliosis. AB - The Chiba Spinal System was developed for three-dimensional correction of scoliosis. The system consists of a 7-mm diameter smooth solid rod, closed and open hooks, and specially designed conical sleeves. The rod does not have ratchets or threads, thus minimizing stress concentrations. The closed and open hooks are attached to the rod using the conical sleeves. The sleeves have longitudinal slits permitting compression during insertion. The outrigger system with a torque wrench is used to correct the deformity in the frontal plane. When correcting lordosis with vertebral rotation, a sagittal correction device may be used. Fifty-two patients with idiopathic scoliosis were operated on with this system from 1986 through 1989. The average correction of the scoliosis was 58%. For the 21 patients with thoracic lordosis less than 0 degrees, the mean preoperative lordosis was -8 degrees, which was corrected to +7 degrees. The mean correction of the vertebral rotation was 24%. Two patients complained of paresthesia of the thoracic region after operation, but this disappeared within 2 weeks. In 32 patients with more than 2 years' follow-up, the mean loss of correction was 3 degrees. One case with instrumentation failure was noted. PMID- 1440006 TI - The variability of response of scoliotic spines to segmental spinal instrumentation. AB - Ninety-two patients (71 idiopathic, 15 neurogenic, 2 Marfan's syndrome, 1 Down's syndrome, 1 osteogenesis imperfecta, 1 Prader-Willi syndrome, 1 Klippel-Trenaunay Weber syndrome), ages 9-49 years, had posterior spine fusion and stabilization with Luque L-rods and sublaminar segmental wires (SSI) for progressive scoliosis. There were no neurologic complications. The average preoperative major curve of 52 degrees (37-113 degrees) initially corrected to 30 degrees (6-94 degrees), and at last follow-up (range, 2-7 years), was 33 degrees (8-90 degrees). There was marked variability in curvature correction and maintenance of correction, with 14 patients progressively decreasing their curvatures postoperatively. Average preoperative Pedriolle vertebral rotation angle for all 92 patients was 16 degrees (4-26 degrees), which initially corrected to 14 degrees (0-24 degrees), and at last follow-up remained 14 degrees (0-23 degrees). Although SSI had little influence on rotation, 12 patients progressively decreased their rotational deformity after operation. Aside from the positive influence of curve flexibility on the degree of postoperative curve correction, the authors could not identify factors explaining how curvature and vertebral rotation responded so variably to SSI. The authors recommend continued use of SSI to stabilize curvatures in osteopenic patients (particularly those with neuromuscular disease), but rotational deformity will probably persist. PMID- 1440007 TI - In vivo analysis of canine intervertebral and facet motion. AB - Using an instrumented spatial linkage, a method for measuring intervertebral motion in vivo was developed and used on six dogs. The segmental motion was recorded as the animals were exercised in routine functions. The standing posture was found to be a repeatable position. During walking, the average excursion between opposing facets was 3.4 +/- 1.3 mm, as the L2-L3 motion segment moved into 2.3 degrees of kyphosis with respect to the standing position. This method has the ability of measuring facet motion (+/- 0.7 mm), vertebral body motion (+/ 0.5 mm), and vertebral body rotations (+/- 0.6 degrees) with suitable accuracy such that it is a useful tool in documenting the in vivo response of a motion segment to surgical procedures. PMID- 1440008 TI - The influence of lordosis on axial trunk torque and trunk muscle myoelectric activity. AB - Force contributions from the facet complex and posterior ligaments during the generation of axial torque are a function of lordosis, and it has been speculated that these forces together with muscular contributions play a role in axial trunk twisting. This study investigated the electromyographic activity of the trunk musculature and torque-generating capacity of the lumbar spine under the conditions of normal lordosis, hyperlordosis, and hypolordosis. Eleven male subjects volunteered for this study. The subjects performed isometric twisting efforts and maximum dynamic twisting efforts at 30 degrees/sec. The myoelectric activity levels (normalized to maximal amplitude obtained from nontwist activities) were quite low despite maximal efforts to generate axial torque (for example: approximately 60% maximum voluntary contraction for latissimus dorsi and even lower for the abdominals). Furthermore, changes in lordosis did not produce any consistent changes in muscle activity, although a hyperlordotic spine produced significantly smaller axial torques, and a hypolordotic spine smaller still. Larger torques were measured during all three conditions of lordosis, as the subjects rotated toward an untwisted position, and lower torques as the subjects rotated away. The opposite trend was observed, however, in myoelectric activity of the agonistic side of latissimus dorsi, the thoracic level of erector spine, and the lumbar level of erector spinae, i.e., larger amplitudes were observed as the trunk was twisted away from the untwisted position. These data suggest that tissues other than muscle (i.e., passive tissue) contribute significantly to axial torque production and that the flexed and twisted spine is less able to resist applied axial torques, possibly increasing the risk of torsional injury. PMID- 1440009 TI - Magnetic resonance signal patterns of lumbar discs in patients with low back pain. A prospective study with discographic correlation. AB - This study presents a large prospective analysis of abnormal magnetic resonance signal patterns in 1,389 lumbar discs in 892 patients with chronic low back pain. Discographic correlations were available at 166 disc levels. Six different signal patterns were identified, and correlations with discograms would suggest that these patterns reflect the differing and progressive changes of lumbar disc degeneration that occur in vivo in patients with low back pain. PMID- 1440010 TI - The natural history of sciatica associated with disc pathology. A prospective study with clinical and independent radiologic follow-up. AB - The purpose of this study was to assess the natural history of sciatica due to lumbosacral nerve root compromise and to evaluate the pathomorphologic changes that accompany the natural resolution of the disease. One hundred sixty-five consecutive patients, 114 males and 51 females, with an average age of 41 years (range, 17-72) and an average duration of symptoms of 4.2 months (range, 1-72) presenting with sciatica thought to be due to lumbosacral nerve root compromise were admitted to the study. The cornerstone of treatment was the serial epidural administration of steroid and local anesthetic by the caudal route on an outpatient basis. Lumbar epidural injection or periradicular infiltration at the appropriate level, confirmed under image intensifier, was the next step before considering surgical decompression. An average of three injections (range, 0-8) was received by each patient. Patients underwent clinical examination and computed tomography. Twenty-three patients (14%) underwent surgical decompression. The remainder were clinically assessed at 1 year after presentation, and 111 were rescanned at the appropriate levels. All conservatively managed patients made a satisfactory clinical recovery: average reduction of pain on the visual analog scale was 94% (range, 45-100), and 64 (76%) of the 84 disc herniations and 7 (26%) of the 27 disc bulges showed partial or complete resolution (chi-square = 20.27, P = 0.0001). Thus a high proportion of patients with discogenic sciatica make a satisfactory recovery with aggressive conservative management, and this recovery is accompanied by resolution of disc herniations in a significant number. Only a small proportion of patients needed surgical decompression. PMID- 1440011 TI - Stenosis of the lumbar spinal canal in vertebral ankylosing hyperostosis. AB - Certain morphologic features frequently observed in radiography or computed tomography (CT) scan in patients with hyperostosis led us to study the association between a narrowed spinal canal and vertebral hyperostosis. Twenty eight items were selected and studied by three different investigators (two rheumatologists and one radiologist) in radiographs and CT scans of 100 patients with acquired stenosis of the lumbar canal, with or without hyperostosis (46 and 54 cases, respectively). The most distinctive points that we suggest can be used as diagnostic criteria of the hyperostotic narrowed lumbar canal are anterior or posterior lateral marginal somatic osseous proliferations, proliferations of the nonarticular aspects of the posterior apophyses, and ossifications of the posterior articular capsule and of the ligaments (yellow ligament, posterior longitudinal ligament, and the supraspinal ligament). Four of these six criteria should be present to establish the diagnosis of hyperostotic lumbar stenosis. The appearance of lumbar hyperostosis on X-ray or CT scans differs from that of simple degenerative changes due to arthrosis, and the hyperostosis can be held responsible for dural compression. PMID- 1440012 TI - Decoupling of bilateral paraspinal excitation in subjects with low back pain. AB - This study compared bilateral paraspinal excitation in normal subjects and subjects with low back pain. Comparison was made between six control subjects and seven low back pain subjects who performed maximum-effort isometric trunk extension in minimum elapsed time at two trunk angles. Electromyographic signals were collected bilaterally from the paraspinal musculature. The time- and amplitude-normalized electromyographic data were analyzed using a repeatability criterion sensitive to temporal and amplitude differences. This analysis showed that low back pain subjects demonstrated temporal and amplitude decoupling of the paraspinal musculature bilaterally. Low back pain subjects also demonstrated clinically meaningful disruptions between paraspinal excitation and isometric trunk extension moment. This method may be useful in quantifying neuromotor control in low back pain for initial and follow-up clinical evaluation for static and dynamic functional tests. PMID- 1440013 TI - Cost-effectiveness of a back school intervention for municipal employees. AB - This study investigated the effect of a back school rehabilitation program on lost work time, lost time cost, medical cost, and number of injuries in municipal employees. Seventy back-injured workers who participated in a 6-week back school were compared on the dependent variables with 70 randomly selected back-injured city employees who had not participated in a back school. Back school participants demonstrated a significant decrease on all dependent variables. Back school participants had significantly fewer injuries in the 6-month postintervention period. No statistically significant differences were found between groups on the time and cost variables. Actual dollars saved in lost time and medical costs between groups was of practical value to the city. Study findings offer support for the back school as a cost-effective measure. PMID- 1440014 TI - Intraoperative evoked EMG monitoring in an animal model. A new technique for evaluating pedicle screw placement. AB - An electric drill was used to introduce holes in the L4 through L7 pedicles in pigs. Constant-voltage stimulating pulses (5.5 V, stimulus rate = 3/sec) were delivered through a ball-tipped probe used to palpate the walls of each pedicle, and observation was made of electromyogram (EMG) evoked from hind limb muscles. Screws were placed in each pedicle hole, and evaluated for absolute voltage necessary to evoke EMG (threshold). At the conclusion of each experiment, screw positions were ascertained by removal and dissection of the lumbosacral spine. Approximately 50% of screw placements resulted in defects of the pedicle. In each of these cases, 5.5 V stimuli delivered through the probe evoked EMG from muscles innervated by adjacent motor axons. Conversely, for those cases where the pedicle was intact, significantly higher voltages were needed to evoke EMG. The authors believe that this is a promising intraoperative technique to simply and reliably identify mispositioned screws, thereby minimizing neurologic complications. PMID- 1440015 TI - Surgical pathology of the intervertebral disc. Is routine examination necessary? AB - A retrospective review of 508 charts of patients undergoing laminectomy for all reasons was carried out with special attention to the preoperative diagnosis, postoperative diagnosis, pathologic diagnosis, and discharge diagnosis. The elimination of routine pathologic examination of surgical discectomy specimens would not have lowered the standard of care; the pathologist's report had no discernible influence on patient management. Unusual clinical features will continue to require careful examination of surgical specimens by the pathologist. Millions of healthcare dollars can be saved by eliminating this routine examination, which is based on outmoded routines. Hospital medical staffs who wish to change this practice must revise their hospital bylaws in keeping with the standards of the The Joint Commission on Accreditation of Healthcare Organizations (JCAHO). PMID- 1440016 TI - Restriction of indication for automated percutaneous lumbar discectomy based on computed tomographic discography. AB - This report details the authors' early experience using the automated percutaneous lumbar discectomy (APLD) procedure, developed by Onik et al., in 97 patients with a disc protrusion. In the evaluation of a herniated disc, we used computed tomography (CT) discography. According to the distribution of the dye inside the disc, five different disc types can be differentiated. With a follow up after 3-7 months, the short-term outcomes of the first 40 APLD-treated patients varied, depending on the shape of the protruded nuclear material. Patients with a broad dye base on CT discography had better short-term outcomes than patients with a narrow dye base. In the next 57 patients we treated with APLD, this tendency was confirmed. The success rate of a consecutive group of patients with a disc protrusion with a broad dye base, treated with APLD, was 80%. In comparison, the patients with a disc protrusion with a narrow dye base had an overall success rate of only 53%. The difference is statistically significant (P < 0.05). The message of this report is that APLD is a useful invasive treatment for patients with a disc protrusion. The outcome depends, however, on the shape of the protruded nuclear material as shown by CT discography, which makes this examination as a conditio sine qua non before treating patients with a disc protrusion with APLD. PMID- 1440017 TI - Unilateral facet dislocation of the lumbosacral junction. AB - Fracture-dislocation of the lumbosacral junction is an extremely rare injury. The authors are aware of only 24 reported cases. Only seven of these were unilateral facet dislocations. In this report, the authors review their experience with four cases of unilateral facet dislocations at the lumbosacral junction. In one of these cases, there was a pre-existing spondylolysis at L5, and the patient sustained a concomitant sacral fracture. From their review, the authors recommend the use of open reduction with internal fixation and lumbosacral fusion as the treatment of choice for this injury. PMID- 1440018 TI - Failure of somite differentiation at the cranio-vertebral region as a cause of occipitalization of the atlas. PMID- 1440019 TI - Traumatic bilateral rotatory facet dislocation of the atlas on the axis. PMID- 1440020 TI - Spondylolisthesis after posterolateral thoracic discectomy. Case report and literature review. PMID- 1440021 TI - Back pain secondary to esophageal perforation in an adolescent. PMID- 1440022 TI - Neural compression due to osteochondral fragments. A report of two cases and review of the literature. PMID- 1440023 TI - Case report. Pelvic rib/digit. AB - In summary, a case of a pelvic rib/digit is presented. Although there is no surgical proof that the finding does indeed represent a sacral rib, its radiographic findings are characteristic enough to warrant this diagnosis. In some respects, the lesion is similar to other cases that have appeared in the literature, but it differs in that it has features of both a pelvic rib and pelvic digit, suggesting a spectrum of development of these anomalous bony structures. PMID- 1440024 TI - Cruciate paralysis after a traumatic upper cervical spine injury. PMID- 1440025 TI - Epidural lipomatosis in steroid-treated patients. PMID- 1440026 TI - Cervical Spine Research Society. 19th annual meeting. Philadelphia, Pennsylvania, December 4-6, 1991. PMID- 1440027 TI - Illness as a lifestyle. The role of somatization in medical practice. AB - Persons with psychological problems who translate their distress into somatic symptoms (somatize) are frequent users of medical care. These patients often have underlying depression, anxiety, obsessive--compulsive symptoms, or personality disorders. Descriptions of the somatizing syndromes are provided in association with recommendations as how to recognize and manage the patient with somatization. PMID- 1440028 TI - A taxonomy of chronic pain syndromes. AB - This article has had as its purpose the delineation of the complexity of the production of pain on an organic basis as opposed to any psychological amplification. The issues addressed apply directly to the problem of spinal pain. Classical nociception arising in the structures of the spine thus would include the application of mechanical and chemical stimuli to muscles, ligaments, apophyseal joint capsules, bone, and other structures with adequate innervation, particularly the anterior dura and its extensions. Disease and injury productive of direct nociception are well understood sources of spinal pain. Less well understood, but of at least equal importance in the spinal pain problem, are the activities within the central nervous system that control the transfer of nociceptive information to the higher centers. These activities account for some of the variability known to occur in the experience of pain. Further, the fact that the nervous system changes its activities in response to chronic pain, particularly that arising from damaged neural elements, is of paramount importance in understanding how chronic pain syndromes differ so greatly from simple nociceptive events. Insidious deafferentation ongoing in spinal nerve roots subject to chronic compression and fibrosis offers a fertile field for research into the origin of permanent pain in patients in whom application of accepted therapies does not result in relief. All of this material must be considered by the clinician who is challenged with analyzing spinal pain problems in patients. PMID- 1440029 TI - The role of neurogenic and non-neurogenic mediators as they relate to pain and the development of osteoarthritis. A clinical review. PMID- 1440030 TI - Chronic cervical pain: radiculopathy or brachialgia. Noninterventional treatment. AB - Chronic cervical pain is not always attributable to radiculopathy. Pain may derive from peripheral myofascial syndromes and/or central inflammatory root irritation from degradation of discal proteoglycans. This concept is presented with its application in 30 patients with follow-up observations up to 30 months. Twelve of twenty-five achieving a pain level of 0 (out of a possible 10), ten of twenty-five had a pain level of 2, and three of twenty-five had a pain level of 4. Five cases were considered to be failures because of patient noncompliance. Treatment was multidisciplinary: aggressive physical medicine, behavioral medicine, vocational, and recreational rehabilitation with the goal of a return to socioeconomic productivity or previous lifestyle, secondary to which pain relief or control follows. Emphasis was placed on the restoration of musculoskeletal physiology to normal with behavioral modification, good body mechanics and the application of engineering/ergonomic principles at work or recreation. PMID- 1440031 TI - Study of experimental cervical spondylotic myelopathy. AB - Most cervical spondylotic myelopathy cases show insidious onset. Experimental cervical spondylotic myelopathy models were made using cats to analyze advancing patterns of myelopathy in the spinal cord and to identify the most responsible factor. Spinal cord compression was applied anteriorly using one screw through the C5 vertebral body or three screws through the C4, C5, and C6 vertebral bodies. Every few weeks, the screws were turned approximately 1 mm at a time up to approximately 50% of the spinal canal. At more than 6 months after final compression, limb function and evoked spinal cord potentials were evaluated. Thereafter, histologic examinations were performed. THE RESULTS: the single compression group showed normal limb function, but the multiple compression group showed sluggish gait. Histologically, mild neuronal decrease in the gray matter was noticeable in the single compression group. Conversely, the multiple compression group showed severe changes in the gray matter and significant changes in the posterior and anterior columns. There was a correlation between the evoked spinal cord potentials and histologic changes. It was clear that multiple compressions to the spinal cord caused more severe deterioration functionally and electrophysiologically as well as histologically than a single compression. PMID- 1440032 TI - Preoperative and postoperative magnetic resonance image evaluations of the spinal cord in cervical myelopathy. AB - To evaluate the morphologic changes of the spinal cord in patients with cervical myelopathy due to cervical spondylosis and ossification of the posterior longitudinal ligament, the authors measured the thickness and signal intensity of the cervical cord with magnetic resonance imaging in healthy adults and patients with cervical myelopathy, and compared these findings. In patients with cervical myelopathy, the preoperative and postoperative magnetic resonance imaging findings were compared with the severity of myelopathy and postoperative results. In healthy adults, the anteroposterior diameter of the cervical cord was 7.8 mm at the C3 level and decreased at lower levels. In the patients with cervical myelopathy, the preoperative spinal anteroposterior diameter was significantly reduced at various levels corresponding to the stenosis site within the vertebral canal. In the group with ossification of the posterior longitudinal ligament, the minimal anteroposterior diameter of the cervical cord tended to decrease with increasing severity of myelopathy. However no relationship was observed between the two parameters in the cervical spondylotic myelopathy group. In the group with ossification of the posterior longitudinal ligament, surgical results were good when the postoperative anteroposterior diameter was increased, whereas in the cervical spondylotic myelopathy group there was no relationship between the two parameters. In the patients with myelopathy, a high intensity area was observed in about 40% of all patients before operation and about 30% after operation. However, the presence or absence of a high intensity area did not correlate with the severity of myelopathy or with surgical results in the group with ossification of the posterior longitudinal ligament and the cervical spondylotic myelopathy groups. PMID- 1440033 TI - Age and gender related normal motion of the cervical spine. AB - The purpose of this study was to develop a clinical method for measuring three dimensional motion of the cervical spine using the CA 6000 Spine Motion Analyzer (Orthopaedic Systems Inc., Hayward CA). Normal values for passive examinations of flexion-extension, lateral bending, rotation, rotation out of maximum flexion, and rotation out of maximum extension were obtained and analyzed for each gender in a group of 150 normal subjects. Gender classifications were further subdivided into age groups, with each decade containing asymptomatic volunteers. Values for each group were compared for differences with respect to age and gender differences. A detailed error analysis was also performed on the interobserver and intraobserver repeatability, differences between passive and active testing, and the use of different fixation devices. Significantly decreased motion differences were found between age groups within gender, and between gender groups in corresponding decades. Results of rotation out of maximum flexion suggest and support earlier conclusions that the rotation of the C1-C2 segment does not decrease with age, but rather increases slightly to perhaps compensate for the overall decreased motion in the lower segments. PMID- 1440034 TI - Benign tumors of the cervical spine. AB - Benign tumors of the cervical spine are relatively infrequent but have a number of common characteristics that aid in the evaluation and treatment of these lesions. The tumors are most common in the first and second decades of life, presenting as pain, neck stiffness and torticollis. In approximately 70%, the lesions are visible on plain roentgenograms and the remainder are well visualized on bone scan and computed tomographic scan. The majority are present in the posterior elements and may be treated adequately with excisional biopsy by curettage. Stage 3 lesions are best treated by marginal excisional techniques and may require adjunctive techniques such as embolization or radiation therapy. The location of the lesion and extent of excision determine the necessity for fusion. PMID- 1440035 TI - Metastatic malignancy of the cervical spine. A nonoperative history. AB - Of 48 patients with spinal metastases treated at the Kenneth J. Norris Cancer Center at The University of Southern California Medical Center in Los Angeles, California between 1984 and 1987, 19 consecutive patients with cervical metastatic disease were identified and followed until death or remission. Prostate, breast, and lung neoplasms accounted for 57% of the cervical metastases. Associated nonspinal skeletal, extraskeletal, or multiple-level spinal metastases were seen in 95% of patients. Mean time from diagnosis of primary tumor to cervical metastasis was 29 months and mean survival after that was 14.7 months. Pain was the initial symptom in 89% of cases. No patient had neurologic deficit and three (16%) had slight radiographic collapse and deformity. Only one (5%) patient had documented instability. All patients had nonoperative treatment with radiotherapy, chemotherapy, or a combination. Irrespective, the pain recurred in all patients by 6 months. Nonoperative treatment may be appropriate in the absence of significant neurologic deficit or instability. The return of symptoms by 6 months warrants alternative modes of therapy. PMID- 1440036 TI - The force exerted by the halo pin. A study comparing different halo systems. AB - Seven different halo systems were evaluated biomechanically to compare the force exerted by the halo pin in each system. In three different experiments torque values of 2, 4, 6, 7, and 8 in lb were applied to the halo pin, and the force at the skull end of the halo pin was measured using a load cell. In the first experiment, the threads on the halo pin were dry, in the second experiment saline was applied to the threads on the pin, and in the third experiment cadaveric bone from the skull was interposed between the pin and the load cell. The results showed that for a given value of applied torque to the pin, the force exerted by the pin end varied widely according to the halo system and whether or not the pin was "lubricated." PMID- 1440037 TI - Anterior cervical discectomy and fusion. A comparison of techniques in an animal model. AB - An animal model for three-level anterior cervical discectomy and fusion was established in the goat. Twenty-one goats underwent surgery, with seven goats in each of three experimental groups. In Group I, all seven goats underwent three level anterior cervical discectomy without fusion. In Group II, each of the seven goats had a three-level discectomy with autogenous bone performed according to the Smith-Robinson technique. In Group III, fresh-frozen allograft bone was used for each of the three-level discectomy and fusion. Each goat was then killed after 12 weeks. Analysis consisted of radiographic review, fluorochrome labeling, biomechanical rigidity and flexion and extension, axial compressive load, and torsion. Histologic analysis was also performed for evidence of fusion and vertebral body histomorphometric analysis. The analysis of results showed that radiographic union was judged to have occurred in 0 of 21 Group I disc spaces, 10 of 21 Group II disc spaces, and 8 of 21 Group III disc spaces. Histologic fusion was judged to have occurred in 0 of 21 Group I goats, 10 of 21 Group II goats, and 0 of 21 Group III goats. The histologic fusion rate was significantly higher in Group II than either Group I or Group III. Biomechanically, the spines that had autogenous bone grafting (Group II) were significantly stiffer in compressive axial load and in extension. Both Group II and Group III were stiffer in flexion than Group I. An evaluation of the peri-endplate vascularity showed that the vascularity measured 10.4% in Group I, 16.7% in Group II, and 8.5% in Group III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440038 TI - Modified Smith-Robinson procedure for anterior cervical discectomy and fusion. AB - Fifty-one consecutive patients with cervical radiculopathy or spondylosis were treated with single or multilevel anterior discectomy and fusion using a modified Smith-Robinson procedure. There were 33 single-level fusions, 16 two-level fusions, and 2 three-level fusions. The three modifications included: 1) the endplates at the fusion level were completely removed with a high-speed bur to exposed bleeding cancellous bone in parallel planes; 2) the Caspar distractor (Aesculap, Burlingame, CA) was used to increase distraction and improve visualization; 3) the tricortical autologous iliac crest bone graft was placed in reverse position, that is, with the cortical cross-section facing posteriorly, creating a stabilizing strut in the middle column. With an average follow-up of 1 year, the fusion rate was 94% (67 of 71 levels). The single-level fusion rate was 97%, the two-level fusion rate was 94%, and the three-level fusion rate was 83%. Of the four nonunions, only two were symptomatic. Results by clinical examination revealed 36 (71%) excellent, 11 (21%) good, 3 (6%) satisfactory, and 1 (2%) poor outcomes. There were no significant disc collapses or extrusions. One patient had an increase in kyphotic deformity of > 5 degrees, none with > 10 degrees kyphosis. There were no wound infections or neurologic complications. The modified Smith-Robinson procedure for anterior cervical discectomy and fusion has led to the successful treatment of cervical radiculopathy and spondylosis with improved results and few complications. PMID- 1440039 TI - Anterior decompression, structural bone grafting, and Caspar plate stabilization for unstable cervical spine fractures and/or dislocations. AB - Fourteen patients who sustained acute cervical spine fractures and/or dislocations with associated posterior ligamentous disruption had anterior decompressions, structural bone grafting, and anterior Caspar plate stabilization. With an average 30-month follow-up, no patient has had loss of fixation. Despite criticism raised from biomechanical testing, the Caspar anterior plate system (Aesculape, Tuttlingen, Germany) may be added to structural bone grafting of unstable cervical fractures and/or dislocations, yielding an in vivo solid construct, which obviates the need for simultaneous posterior stabilization. PMID- 1440040 TI - Spontaneous fracture of the odontoid process in rheumatoid arthritis. AB - Six cases of spontaneous fracture of the odontoid process in rheumatoid arthritis are presented. Fifty-one patients with atlantoaxial subluxation in rheumatoid arthritis underwent surgery between 1981 and 1990. This included six patients (in 10%) who had subluxation accompanied by fracture of the odontoid without apparent trauma. The mean patient age was 58 years and all had a long history of rheumatoid arthritis. No trauma was considered to be the cause of the fracture. This is a fracture caused by erosion and osteoporosis of the odontoid process due to rheumatoid synovitis, aging and steroid therapy. In addition, another cause is a dynamic load produced from the instability accompanying atlantoaxial subluxation working on the odontoid in cervical extension. It is important remember that the odontoid process is susceptible to spontaneous fracture. PMID- 1440041 TI - Treatment of lower cervical spinal injuries--C3 to C7. AB - Injuries of the lower cervical spine are categorized according to the morbid anatomy of the lesion. Most often, such injuries are successfully treated by surgery through a posterior approach. After anatomic restoration, internal fixation with plates and screws provides for stability and arthrodesis. Of 221 cases of lower cervical spine injuries, posterior stabilization was accomplished in 89%. There was no secondary displacement in 85% of cases. PMID- 1440042 TI - Management of fracture separations of the articular mass using posterior cervical plating. AB - Fracture separations of the articular mass are a specific group of unilateral facet fractures that must be considered separately because of their unique two level instability. This fracture pattern involves a longitudinal fracture of the lamina and a fracture of the pedicle on the same side of the spine at the same level. It is characterized roentgenographically by horizontalization of the lateral mass, with a mean translation of 4.6 mm and a mean angulation of 6.9 degrees. In this study the deformity most commonly occurs at the level below the fracture (19 patients) but also occurred at the level above (5 patients). There is a high incidence of neurologic involvement (14 of 24 patients), most often radicular in nature. This injury results in two level instability requiring a three-level, two-interspace stabilization. All twenty-four patients in this series underwent posterior cervical plating with either an asymmetric (8), symmetric (9) or porte manteau (7) construct. Statistically significantly better results (P < 0.05) were achieved with either a symmetric or porte manteau construct. Complications including neurologic deficit and loss of correction were more frequent in the asymmetric group. PMID- 1440043 TI - [Method for estimating the population risk attributable to a transfer station of municipal solid waste]. AB - Due to the great volume of municipal solid waste that is produced daily in the Metropolitan Area of Mexico City a sound management has been an impossible task. This is why during the past few years solid waste transfer stations have been constructed in the City, allowing a more efficient solid waste collection. The attributable risk to the population's health for the operation of such stations needs to be assessed in order to have them working within the urbanized areas without posing a potential risk to the health of the inhabitants of the inhabitants of the surrounding areas. PMID- 1440044 TI - [Risk of tuberculosis infection in the health jurisdictions of Jalisco, Mexico]. AB - This paper reports an evaluation of the risk of tuberculosis infection in school children in the sanitary jurisdictions of Jalisco, Mexico. It also compares the official figures of incidence of smear-positive pulmonary tuberculosis with those estimated with this epidemiological indicator. The study included 6,469 first grade children, six to seven years old, from 95 state schools. We skin-tested 4,260 of them with 2 TU PPD. Sixty per cent of the children tested were vaccinated with BCG. This proportion varied between the jurisdictions: from 43 per cent in Tepatitlan to 70 per cent in Ameca. The rate of tuberculosis infection was 6.3 per cent, with differences between children with a BCG scar and those with no scar (7.4% and 4.4%, respectively). We also found differences in the annual risk of infection between the jurisdictions. The annual risk was 0 per cent in Lagos de Moreno and 1.60 per cent in Ameca. With the exception of two jurisdictions, the incidence of smear-positive pulmonary tuberculosis estimated with this indicator is several times higher than that officially reported. PMID- 1440045 TI - [Regionalization in health: an instrument for jurisdictional planning]. AB - This study carried out the regionalization of Sanitary Jurisdiction No. III seated in Cuautla, Morelos, consisting of 16 of a total of 33 municipalities in the state of Morelos. This regionalization was carried out through the delination of areas sharing similar socioeconomical and demographic characteristics (SED). Subsequently, the major health hazards and the intraregional distribution of human health resources (physicians and nurses) and infrastructure services (institutional health centers) were identified for each region. The aim of this work was to devise an instrument for a better understanding of and approach to health problems at a juridictional level and to pave the way for health planning that would be congruent with regional characteristics and needs. Health sector efforts would be directed towards the promotion of preventive health care with greater efficiency and equity. In order to regionalize the jurisdiction, 17 SED indicators were studied in each of the 16 municipalities. Analysis was performed using the Principal Components Method (MCP) and an epidemiologic score. As a result, the sanitary jurisdiction was divided into three regions: Region I, with the best SED conditions, Region II, with moderate SED conditions and Region III with the lowest SED conditions. The results of this study show that there is an inverse relationship between the intraregional distribution of health resources with respect to the delineated regions and the health resources with respect to the delineated regions and the health needs and problems found in each one. Region III showed the worst SED conditions and the highest incidence of disease. It proved to be the region which had the greatest lack of material and human health resources, the latter having the lowest technical training level in all of the jurisdiction. In contrast. Region I had the best SED conditions and the lowest incidence of disease. It also had the highest number of material and human health resources, the latter having a high level of preparation. This situation is opposite to the national health policies in regards to equity "...give more benefits to the more vulnerable groups..." PMID- 1440046 TI - [The migration process as risk factor in chronic malnutrition of pre-school children from Jalisco]. AB - The purpose of this study was to identify risk factors in the family's migratory profile of preschool children with chronic malnutrition. A comparative observational study was conducted, including 511 12 to 60 months old children from childcare centers in the Jalisco sugar cane area, from February to March 1988. We evaluated their nutritional status using anthropometric indicators and Waterlow's classification. Their migratory history included information on place of origin, migratory mobility, cause of immigration, sociodemographic characteristics of parents and history of siblings who died under five years. The prevalence of malnutrition was 79 percent per 100 preschool children (68.5% adapted, 21.5% acute chronic and 10.4% acute). Factors associated with chronic malnutrition (OR greater than 1 CI 95%) included: coming from a poverty stricken population and being permanent migrants. A significant difference (p less than 0.05) was found among children of parents who were jobless at the time of migration. These findings could be used to justify the implementation of nutritional epidemiologic surveillance and intervention programs. PMID- 1440047 TI - [Pregnancy, labor, and puerperium: concepts and practices of midwives in the state of Morelos]. AB - In Mexico a combined type of care for the health-sickness phenomenon exists, where three systems interact: domestic, academic and traditional medicine. In relation to reproductive health, in the state of Morelos approximately 50 per cent of women in rural areas receive attention from traditional birth attendants, who make up one of the principal resources of traditional medicine. The goal of this study was to gather knowledge about and describe the concepts, resources and practices used by traditional birth attendants in their care during pregnancy, birth and puerperium; and likewise to determine their socio-demographic characteristics, their geographic distribution, their number and the level of training which they possess. A census based on three sources was carried out in which information about seven basic variables was sought. This information was completed with structured interviews with key informants which allowed the definition of a profile of the different types of traditional birth attendants according to the population they care for and the resources they use. The most relevant results indicate that 630 traditional birth attendants are distributed throughout the 32 municipalities of the state, with an average age of 52 years and 50 per cent having attended training courses. 17.5 per cent fall within the category of traditional birth attendant, 50 per cent are trained empiricists and 11.6 per cent are non-trained empiricists. The 20 per cent did not fit this typology. The strong social and cultural identification that exists between traditional birth attendants and their patients indicates the need to incorporate this valuable resource in rural reproductive health programs. PMID- 1440048 TI - [Common personality traits in obese individuals]. AB - This study is part of an interdisciplinary investigation in which the obese patient is evaluated from different aspects. This paper deals with the psychometric evaluation of obese people to search for common personality traits in obese patients attending the Weight Control Program offered by the Nutrition Project of ENEP Iztacala. The results show that differences do exist between obese and non-obese people, especially on some scales of the Inventory of Temperamental Traits. PMID- 1440049 TI - [The supply of physicians in Mexico: excess and shortage]. AB - The purpose of this paper is to find out whether a decrease in the number of medical undergraduates doing their social service has any influence on the quantity of medical services provided by health care institutions in Mexico. Spearman's Rank Test was used to correlate the number of medical undergraduates and the number of services. Data for analysis were taken from the statistical information bulletins of the Ministry of Health for the decade of the 1980's. The analysis found that there is a significant correlation between the number of medical undergraduate and the number of primary health care services provided, and that this correlation disappears in the cases of secondary and tertiary health care services. The results underscore the importance of reconsidering the adequate number of physicians required to satisfy the health care needs of the Mexican population. PMID- 1440050 TI - [Problems identified by geriatric evaluation at a nursing home]. AB - A geriatric evaluation was carried out in a group of 37 elderly nursing home residents. A complete history and physical examination was performed in all the patients. We identified 185 new medical problems in the patients, 40.7 per cent of whom were rehabilitation candidates. A functional status evaluation on daily activities showed dependency in 56.8 per cent of the patients while in daily instrumental activities 51.3 to 81 per cent of the patients required assistance. A mental status evaluation showed abnormalities in 46.8 per cent of the patients. This analysis shows the need of implementing this particular form of evaluation of elderly patient in our community and nursing homes. PMID- 1440051 TI - [Self-medication in a urban population of Cuernavaca, Morelos]. AB - This work contains the results of a study on the prevalence of family drug consumption. In our country, self medication should be considered a public health problem due to the population's lack of medical education. Nevertheless, this problem has not been properly studied. For this reason, we completed an exploratory study in an urban population of Cuernavaca, Morelos, Mexico. Its purpose was to gather information about the situation of drug consumption and self medication. A survey was given to 373 domestic groups from the Carolina neighborhood in Cuernavaca. These groups were selected through systematic and probabilistic sampling. A total of 1,537 individuals of all ages were surveyed with an average of four participants per domestic group. Thirty one per cent of those surveyed had consumed drugs during the two weeks prior to the survey. Of these consumers, 53.3 per cent did it through self medication, and 64.9 per cent of them were females. If classified by age group, the highest consumer rate, 7.6 per cent, belonged to the users between 25 to 44 years. If the classification is done by sex and age, women between 25 to 44 years consumed more antibiotics and analgesics which were obtained over the counter. Among the surveyed population, the consumption of medicines was done primarily through self medication, mostly administered by women, and most frequently consumed by infants under one year of age. This phenomenon occurred regardless of the availability and accessibility of public and private health services. The data collected do make us identify women as a fundamental element in the consumption of drugs and self medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440052 TI - [Education needs for the development of binational programs of health care]. AB - The purpose of this article is to describe a research project carried out in Virginia, Maryland, Delaware and Pennsylvania. The main objective was to find out the continuing education needs of the staff implementing Primary Health Care (phc) programs developed with Mexican migrant workers. The methodology was based on applied research techniques. It was divided into two stages. The first stage was an interview which was applied to the coordinators of three programs: medical care, health education and sexually transmitted diseases. The second part of the methodology was to design a continuing education course with the input of the first stage. The course was implemented in the School of Public Health of Mexico in 1990. It had three main components: sociology and health in Mexico; health programmes in Mexico, and traditional medicine. The course also included a set of visits to clinics, hospitals and curanderos. The course has generated a group of scholars who are planning projects in this field to define the health needs of the migrant Mexican population in that area and the impact in Mexico. The course is also part of the regular Continuing Education Programme of the School of Public Health of Mexico now. PMID- 1440053 TI - [Smallpox in the Mexican Republic. 1954]. PMID- 1440054 TI - Radiation hybrids for mapping and cloning DNA sequences of distal 16p. AB - Three hundred fifteen radiation hybrids (RH) were isolated using a monochromosomal cell hybrid containing chromosome 16 only. A panel of 18 RH, which showed breakpoints among four markers (3.15, 26.6, 3'HVR, and 5'HVR) mapping in the distal portion of 16p, were selected and characterized for the retention of nine additional DNA sequences already localized in this region, and for one centromeric sequence. One or more breakpoints were identified in nine of the 12 intervals defined by the 13 single-copy sequences used. This panel of RH represents a tool for the construction of a detailed physical map of the distal part of 16p and for cloning sequences located in the proximity of disease genes. Three inter-Alu DNA sequences, amplified from one of these RH containing the autosomal dominant polycystic kidney disease (PKD1) gene, were cloned and mapped in the panel. Sequencing of the ends of one of three clones showed a (CAAA)n repeat, which revealed a two-allele polymorphism. PMID- 1440055 TI - Gene targeting using a mouse HPRT minigene/HPRT-deficient embryonic stem cell system: inactivation of the mouse ERCC-1 gene. AB - A convenient system for gene targeting that uses hypoxanthine phosphoribosyltransferase (HPRT) minigenes as the selectable marker in HPRT deficient mouse embryonic stem (ES) cells is described. Improvements to the expression of HPRT minigenes in ES cells were achieved by promoter substitution and the provision of a strong translational initiation signal. The use of minigenes in the positive-negative selection strategy for gene targeting was evaluated and the smaller minigenes were found to be as effective as a more conventional marker--the herpes simplex virus thymidine kinase gene. Minigenes were used to target the DNA repair gene ERCC-1 in ES cells. A new HPRT-deficient ES cell line was developed that contributes with high frequency to the germ line of chimeric animals. The ability to select for and against HPRT minigene expression in the new HPRT-deficient ES cell line will make this system useful for a range of gene-targeting applications. PMID- 1440056 TI - Molecular cloning of a gene involved in methotrexate uptake by DNA-mediated gene transfer. AB - A methotrexate-resistant Chinese hamster ovary cell line deficient in methotrexate uptake has been complemented to methotrexate sensitivity by transfection with DNA isolated from a wild-type Chinese hamster ovary genomic cosmid library. Primary and secondary transfectants, which contain a limited number of cosmid sequences, have been shown to regain methotrexate sensitivity and to take up methotrexate. Furthermore, the DNA from three cosmid clones, isolated from a primary methotrexate-sensitive transfectant, after transfection rescued the methotrexate-resistant phenotype at a high frequency. Restriction endonuclease analysis of the DNA of these cosmid clones indicated that they overlapped extensively and shared two regions of Chinese hamster ovary DNA of 6.6 kb and 20.6 kb. These observations indicate that a gene involved in methotrexate uptake is contained in its entirety within one of these regions. This is the first report of the functional molecular cloning of a gene involved in methotrexate uptake. A general strategy is also described for screening large cosmid libraries from primary transfectants. PMID- 1440058 TI - New chromosomal mapping assignments for argininosuccinate synthetase pseudogene 1, interferon-beta 3 gene, and the diazepam binding inhibitor gene. AB - Argininosuccinate synthetase pseudogene 1 (ASSP1), interferon-beta 3 (IFNB3) gene, and diazepam binding inhibitor (DBI) gene have previously been mapped to human chromosome 2. Their nucleotide sequences, recorded in the GENBANK data base, were used to generate DNA primers to amplify specific sequences using the polymerase chain reaction (PCR). These primers failed to amplify DNA sequences when used to analyze microcell hybrid clones containing human chromosome 2. In order to map these genes, a panel of somatic cell hybrids was analyzed by PCR with these primer sets. The results of these experiments place ASSP1 sequences on human chromosome 6, IFNB3 on human chromosome 8, and DBI on human chromosome 6. PMID- 1440057 TI - A gene that partially complements xeroderma pigmentosum group A cells maps to human chromosome 8. AB - A gene that partially complements sensitivity of xeroderma pigmentosum cells of group A to UV irradiation has been mapped to human chromosome 8. Isolation of this gene has previously been described. A cDNA clone pEMKR that represents part of this gene was used for mapping. Based upon the nucleotide sequence of pEMKR, a set of oligonucleotide primers were designed for PCR amplification of DNAs from hybrid cell lines. A panel of rodent-human hybrid cell lines representing the total human genome was screened by PCR and Southern blot analysis for chromosomal assignment of this gene. PCR amplification and hybridization occurred only in the case of human and hybrid cell lines that contained human chromosome 8. The pEMKR thus represents a different gene than a DNA repair gene XPAC that has been mapped to human chromosome 9. PMID- 1440059 TI - [Breast cancer: trends from 1964 to 1990. Results of a long-term study]. PMID- 1440060 TI - [Radiologic diagnosis and therapy of stenosed or occluded hemodialysis shunts]. PMID- 1440061 TI - [Lymph node metastasis-recurrence following head and neck tumors: computed tomography]. PMID- 1440062 TI - [The place of sonography in surgical intensive care patients]. PMID- 1440063 TI - [Picture quality, tolerance, acceptance and longevity of a barium sulfate suspension (Micropaque CT) as an oral intestinal contrast medium for abdominal computed tomography]. PMID- 1440064 TI - [X-ray study of the upper gastrointestinal tract. 2. Stomach and duodenum]. PMID- 1440065 TI - [Technique and indications for percutaneous transluminal angioplasty of the arteries supplying the arm]. PMID- 1440066 TI - [Hypomelanosis of Ito: detection of an ectopic cortical area in the MR tomogram]. PMID- 1440067 TI - [Evaluation and classification of CT findings in work-related lung and pleural changes in accordance with the ILO pneumoconiosis classification]. PMID- 1440068 TI - [Radiobiological research. A basis for advances in clinical radio-oncology]. PMID- 1440069 TI - [Incisional, stab and gunshot wounds of the abdomen and thorax]. AB - The authors give an account of the incidence and prognosis of the mentioned injuries treated during the past five years (1987-1991) at the surgical department of a district hospital in the centre of Prague. During the past two years a marked increase of these injuries was recorder. A total of 10 persons with abdominal injuries had ambulatory treatment and nine patients with injuries of the chest. During the same period 24 patients with abdominal injuries and 6 patients with chest injuries were hospitalized as well as four patients with combined abdominal and chest injuries. Nineteen ambulatory patients and 34 hospitalized patients during the five-year period are an ever increasing group of casualties who suffered injuries usually when drunk or due to violence. PMID- 1440070 TI - [Extensive corium grafts]. AB - Even in our times of revolutionary advances in the technology and operative techniques in plastic surgery, the corium is a material with multiple applications and can be found in the patient at varying thickness. The aim of the article is to show that its indication to reinforce flaccid musculature or to cover muscular defects of the abdominal wall is fully justified even in a time of routine use of plastic nets. PMID- 1440071 TI - [Is cooling harmful to wounds?]. AB - An adequate blood supply and stable temperature of the wound are very important for the healing process. During healing of a wound we can observe in the surrounding area two of rises temperature. The first rise is produced by the inflammation in the close vicinity of the wound and its peak is approximately on the 5th-10th day after treatment. The second peak can be found locally after 10 days. It is due to new formation of capillaries and thus a more ample blood supply of the wound and an increased tissue metabolism in the area surrounding the wound. Algidity affects healing in an adverse manner. The author mentions the results of some experiments which provide evidence of the favourable effect of stable temperature on wound healing. This can be achieved by adequate dressing technique and a correct procedure when changing dressings. Wounds must not remain undressed for prolonged periods to avoid drying up and cooling. PMID- 1440072 TI - [Complications of mediastinoscopy examinations]. AB - In 1970-1990 in the Institute of Lung Diseases in Prague a total of 180 mediastinoscopies were performed. In the submitted paper the authors discuss 169 of these examinations. In this group 20 examinations were associated with a peroperative or postoperative complications, i.e. a total of 12% of the examinations. However, only in three patients, i.e. cca 1.8% from the total number serious complications were involved which were unequivocally specific for mediastinoscopy. In two instances massive haemorrhage occurred from lacerated mediastinal vessels associated with superior vena cava syndrome and in one case pneumothorax developed. All these complications were controlled by surgical intervention made in time. The most frequent complication after mediastinoscopic examination was retention of a serohaematoma in the wound--this was recorded 11 times. The cause of its development is the method of preparation and anatomical conditions in the pre- and paratracheal space. The percentage of this complication can be reduced by using active drainage of the mediastinum. PMID- 1440073 TI - [Evaluation of chemical necrectomy of burns using benzoic acid]. AB - The author tries to define indication for chemical necretomy. He also discussed views regarding the toxicity of benzoic acid and thus attempts to express its use quantitatively. PMID- 1440074 TI - [Postgraduate education in oncologic surgery]. PMID- 1440075 TI - [Errors and deficiencies in prehospital care of surgical patients]. PMID- 1440076 TI - [James Douglas--the name and the man]. PMID- 1440077 TI - [Adverse events and adverse reactions associated with drugs--important actual spontaneous reporting of the drug event]. PMID- 1440078 TI - [Amyloidosis associated with rheumatoid arthritis after total joint replacement]. AB - Rheumatoid arthritis patients who had secondary amyloidosis have been studied retrospectively. There were eight patients out of 105 rheumatoid arthritis patients who had total joint replacement surgery from 1979 to 1990 in our institute. The grade of inflammation, renal and hepatic function have been compared with the RA patients without amyloidosis pre- and post- operatively. All of eight patients was female, and their average age at the diagnosis of amyloidosis was 57.8 year-old (range 4-76 year-old). The average preoperative period was 14.4 years (range 4-27 years), and the secondary amyloidosis had been diagnosed at the time of 3.8 years (range 1-9 years) after operation. The major clinical features leading to the diagnosis were gastrointestinal disturbance in six cases and renal dysfunction in two cases. The data of the renal function of amyloidosis patients showed slightly lower than that of the RA patients without amyloidosis, and showed significantly decrease postoperatively. The white blood cell (WBC) count was higher at the time of operation in the amyloidosis patients and showed continuous increase postoperatively. Lansbury index, alpha 2-globulin and WBC count did not improve in the amyloidosis patients during three years after operation. On the contrary, the patients without amyloidosis improved in these clinical data during the same period. Three amyloidosis patients died of renal failure and one died of bronchopneumonia. The average survival period was 1.8 years (range 1-5 years) after diagnosis of amyloidosis, and was 6.3 years (range 2-10 years) after operation in these four patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440079 TI - [Reassessment of measurement of anti double-stranded DNA antibodies by Farr's assay using double-stranded DNA from E. coli and application of DNA binding Activities in high salt solution]. AB - Farr's assay using double-stranded (ds) DNA from E. coli is a most sensitive and specific method for the detection of anti ds-DNA antibodies in patients with systemic lupus erythematosus (SLE). Because of the lack of sufficient DNA antigens, however, final antibody titers were hardly determined when the sera contained antibodies titered more than 100U/ml (or more than 60 per cent by DNA binding activities). In such sera DNA binding activities were measured by using ds-DNA tracer adjusted final concentration of NaCl to 125 mM. Higher binding activities measured by high-salt tracer are obtained significantly in SLE patients groups with nephrotic syndrome, proteinuria, cast, renal failure, diffuse proliferative nephritis, low serum complement levels, anemia and/or low IgG/IgA levels compared with the patients who lacked these clinical findings. In contrast the patients with digital rash or cramp showed significantly lower high salt binding activities. The patients with pleuropericarditis tended to have lower bindings. The non-lupus patients including MCTD also had lower levels. These clinical characteristics could not be evaluated by standard Farr's assay. High-salt bindings suggest the presence of high avidity antibodies and also partly may mean the high levels of low avidity antibodies. The application of high-salt binding activities, thus, is a useful tool for the evaluation of clinical characteristics of SLE patients who had high levels of anti ds-DNA antibodies by standard Farr's assay. PMID- 1440080 TI - [Clinical characteristics and prognosis of secondary amyloidosis in patients with rheumatoid arthritis--renal involvement and therapy]. AB - Secondary amyloidosis is an important complication that may have a strong influence on the prognosis of patients with rheumatoid arthritis (RA). We studied 21 RA patients with secondary amyloidosis. The two major initial signs were gastrointestinal symptoms and renal involvement. When 15 of the 21 patients were diagnosed as having secondary amyloidosis, they displayed renal involvement including proteinuria, hematuria and hypercreatininemia. The 15 patients with amyloidosis were either subjected to dialysis or died within 35 months on the average. The causes of death in 13 patients were cardiac failure, gastrointestinal bleeding and infection, which were strongly implicated with renal failure. Dialysis was applied to seven patients. Three of them were maintained with chronic dialysis. We discussed the induction-time and the method of dialysis in patients with amyloidosis secondary to RA. PMID- 1440081 TI - [Clinical usefulness of the measurement of type-II procollagen carboxypeptide (C II propeptide, pColl-II-C) in synovial fluid as a marker of collagen metabolism in cartilage]. AB - Type-II procollagen-C-peptide (pColl-II-C) in synovial fluids was studied in 319 patients with osteoarthritis (OA; 151), rheumatoid arthritis (RA; 141), traumatic arthritis (TA; 27) and 15 healthy volunteers using the newly developed ELISA kit. The mean levels of pColl-II-C in synovial fluids of healthy controls, OA, TA, and RA were 0.3 +/- 0.1 ng/ml, 5.9 +/- 0.3 ng/ml, 6.8 +/- 1.4 ng/ml and 1.1 +/- 0.1 ng/ml, respectively. pColl-II-C levels in synovial fluids of OA and TA were significantly higher compared to those of healthy controls and RA. It was also demonstrated that pColl-II-C levels could reflect the quantitative and qualitative change of cartilage metabolism. Therefore, the quantification of this molecule in synovial fluid could be beneficial to know the synthetic activity of type II collagen of chondrocytes, since pColl-II-C is a part of the precursor molecule of type II collagen. PMID- 1440082 TI - [A case of adult onset hypophosphatemic vitamin D resistant osteomalacia]. AB - A case of adult onset hypophosphatemic vitamin D resistant osteomalacia is described. A 40-year-old female who complained of thorax and lumbar pain and gait disturbance was admitted to our hospital on 7 November, 1988. The patient had hypophosphatemia with normal plasma calcium, parathyroid hormone and 25-hydroxy vitamin D3 concentrations, but had decreased tubular reabsorption of phosphate and decreased plasma 1, 25-dihydroxy vitamin D3 concentrations. The iliac crest bone biopsy showed osteomalacic changes. The 99mTc-MDP bone scintigram showed evidence of increased bone turnover with raised plasma alkaline phosphatase concentrations. After treatment with oral 1 alpha-hydroxy vitamin D3 (3-6 micrograms/day) and intravenous or oral phosphate supplement (0.47-1.74g/day), the subjective and clinical findings improved. PMID- 1440083 TI - [A case of late-onset SLE complicated with EDTA-dependent pseudothrombocytopenia]. AB - A 57-year-old man was admitted to our clinic with complaints of proximal myalgia in extremities. He was diagnosed as late-onset SLE based on the findings of pleuritis, pericarditis, arthritis and antibodies to DNA and cardiolipin. Aggregation of the platelets and the decreased counts of platelets were observed when EDTA was used as anticoagulant for the blood tests. However, the platelet aggregation was not noted with normal counts of platelets when Heparin Theophylline was used as anticoagulant. From this observation, EDTA-dependent pseudothrombocytopenia was diagnosed and IgM class of EDTA-dependent anti platelet antibody was detected by means of flow cytometry. Administration of prednisolone at 40mg/day reduced the symptoms and EDTA-dependent pseudothrombocytopenia, and EDTA-dependent anti-platelet antibody disappeared. His clinical course suggested that EDTA-dependent pseudothrombocytopenia was closely associated with the disease activity of SLE. PMID- 1440084 TI - [Gold-induced severe cholestatic jaundice in rheumatoid arthritis patient and effect of repeated steroid pulse therapy]. AB - A 32-year-old female with early stage of rheumatoid arthritis (RA) developed anorexia, pruritus, dark urine, pale stool and jaundice 3 weeks after initiation of chrysotherapy. She was administered a total of 35mg of gold sodium thiomalate (GST) intramuscularly and auranofin 6mg per day orally. Liver function tests and biopsy specimens showed severe cholestatic jaundice. Prednisolone 30mg per day and plasma exchange were started. No response however was obtained and the total bilirubin level gradually increased. Steroid pulse therapy, 1000mg methylprednisolone for successive 3 days as one therapy unit, was repeated 4 times. Liver functions were then gradually improved. Gold induced hepatotoxicity is a rare complication. We concluded that the hepatotoxicity in this case was caused by allergic reaction against GST and repeated steroid pulse therapy was very effective to these conditions. PMID- 1440085 TI - [A case of rheumatoid arthritis complicated with pseudotumor around odontoid process successfully treated by methotrexate]. AB - A 69-year-old-female with a history of rheumatoid arthritis since 1975 had suffered from dysesthesia of extremities since October 1989. Radiating pain and weakness occurred when she tried to stand up on Dec. 25 in 1989. She was admitted to our hospital in October 1990. Physical examination showed emaciation, hypesthesia of extremities, hypesthesia over the right chest and back, impaired vibration and position sense, and hyperreflexia. Laboratory findings revealed that the erythrocyte sedimentation rate was elevated to 46mm/hr, rheumatoid factor (RF) to 83.1IU/ml and CRP to 3.7mg/dl. Her blood sugar was high and she was diagnosed as having diabetes mellitus. Cervical X ray film showed atlanto axial subluxation. A pseudotumor around the odontoid process bulging into the spinal canal and compression of the upper cervical cord was observed by MRI. In spite of administration of bucillamine (100mg/day), the size of pseudotumor did not change. Methotrexate (MTX) at a dose of 5mg/week was started in February 1991 and the pseudotumor decreased in size with a concurrent reduction of ESR, RF and CRP. However, the high intensity lesion by T2 weighed image did not change and dysesthesia persisted. The pseudotumor was thought to be due to pannus and it was revealed that MTX was effective for reduction. The persistent dysesthesia was probably due to the degeneration of the upper cervical cord, although diabetic neuropathy may also have played a role. PMID- 1440086 TI - [An autopsied case of progressive systemic sclerosis with anti Wa antibody who showed a rapid progression]. AB - An anti Wa antibody was reported as a new t-RNA related protein antibody in 1986. This autoantibody is now considered specific for the diagnosis of progressive systemic sclerosis (PSS). Up to date only 5 cases with anti Wa antibody have been identified. We report here an autopsied case of PSS with this antibody. A 53 years old female was admitted to our hospital because of dry cough and dyspnea in Sep 1987. There were fine crackles and chest X ray revealed interstitial pneumonia. The progressive respiratory failure was treated by steroid pulse therapy effectively. Sclerotic skin changes of hand began to appear in Sep 1988 and rapidly progressed to arms, chest and forehead by Dec 1988. A skin biopsy confirmed PSS changes. An anti Wa antibody was detected by double immunodiffusion and the protein antigen was associated with t-RNA when immunoprecipitation was conducted. She died of heart failure in July 1989. An autopsy revealed the diffuse fibrotic change of the heart and the lung. Cases with anti Wa antibody were shortly reviewed from the literature. PMID- 1440087 TI - [A systemic lupus erythematosus patient with multiple aseptic bone necroses, thrombosis of superior mesenteric artery and anti-phospholipid antibody]. AB - A 38 year old woman with systemic lupus erythematosus (SLE) was admitted because of epigastralgia and fever. The diagnosis of SLE was made 22 years ago based on Raynaud's phenomenon, butterfly rash, hair loss, photosensitivity and positive antinuclear antibody. She had episodes of consciousness disturbance, transient visual disturbance of the left eye, and a necrosis of the left big toe. She underwent artificial arthroplasty of bilateral femoral heads 11 years ago, when multiple aseptic necroses of thirteen bones were found, and when anti-cardiolipin (CL) antibody was found to be positive. An echogram of abdomen suggested an obstruction of superior mesenteric artery (SMA) when she was admitted. Selective angiography revealed a complete obstruction of SMA and splenic artery, and incomplete obstruction of celiac artery. Conservative treatment with urokinase infusion and prednisolone 50 mg/day was not effective, and small intestine and right colon were resected on the 23rd hospital day. The pathological examination showed thrombosis of SMA. There was no evidence of arteritis or atherosclerosis. Anti-CL antibody and lupus anticoagulant were positive on admission, but the level of both anti-DNA antibody and complement was normal. Therefore, it was suggested that the thrombosis was related with anti-phospholipid antibody. The characteristic clinical feature were multiple aseptic bone necroses and thromboses of several arteries. We discussed the relationship of thrombosis and the etiology of multiple bone necrosis in this case with anti-phospholipid antibody. PMID- 1440088 TI - [Tubulo-interstitial nephritis (TIN) with no glomerular lesions, distal renal tubular acidosis and asteatosis cutis in a patient with systemic lupus erythematosus (SLE): a case report]. AB - We report a 28-year-old woman with systemic lupus erythematosus (SLE) who showed tubulo-interstitial nephritis (TIN) without any glomerular changes. In 1990, she was admitted to our hospital, complaining of anorexia, vomiting and persistent high fever. Laboratory findings showed proteinuria, pancytopenia, hypocomplementemia and positive for antinuclear antibody, anti-DNA antibody, anti Sm antibody, anti-SSA antibody and anti-SSB antibody. We made a diagnosis of SLE. Furthermore, distal renal tubular acidosis and asteatosis cutis were revealed. The diagnosis of Sjogren's syndrome was not made. We treated with high-dose prednisolone (60mg/day) and achieved improvement of symptoms and laboratory data. Open renal biopsy showed TIN without any glomerular changes. Predominant TIN is very rare in SLE. We discussed its pathogenesis and relation to the renal lesions of Sjogren's syndrome. PMID- 1440089 TI - [A case of rheumatoid arthritis associated with progressive systemic sclerosis and primary biliary cirrhosis in the presence of various autoantibodies]. AB - The patient (a 49 year-old, female) had been diagnosed in Apr. 1987 as having rheumatoid arthritis (RA) following the history as chronic non-A, non-B hepatitis for 4 years. Progressive systemic sclerosis (PSS) and primary biliary cirrhosis (PBC) were also defined on 1989 in the same patient mainly due to proximal scleroderma and histological findings of liver biopsy. On the other hand, the coexistence of rheumatoid factor, anti-Scl-70 antibody, anti-mitochondrial antibody (anti-MC, anti-MD and an unidentified fraction) and anti-centromere antibody have been observed with marked polyclonal hypergammopathy in her sera since July 1990. Her disease activity has been controlled well with the administration of D-penicillamine and ursodeoxycholic acid during recent clinical course. Few cases of RA associated with PSS and PBC, showing various autoantibodies as a disease marker in sera, have been reported. In order to evaluate the mechanisms of autoimmune disease especially chain reaction of autoimmunity, it should be important to accumulate the reports concerning such cases. PMID- 1440090 TI - [Mechanisms of the production of anti-DNA auto antibodies]. PMID- 1440091 TI - [Hemostasis screening in the emergency laboratory]. AB - PURPOSE: While automation of laboratories is of great value for analysts, as it makes technical work easier, and for clinicians, as the results are available in a shorter time, the requests increase strikingly bringing about higher costs. The emergency laboratory is an example of what happens in the general laboratory. In order to make an estimate of this subject, the haemostasis screening was chosen since it is a recently automated technique in that laboratory, attention being paid to the aim and indication of the screening and its economical burden. MATERIAL AND METHODS: A study of the haemostasis screening performed during July 1990 was carried out of considering the 24 hours per day work. The requests were classified, in accordance with their indication, as diagnostic, pre-surgical, therapeutic or unknown; the justification and purpose of those requests was also examined. RESULTS: The total number of studies performed in that month was 1,273, with a daily mean of 41, as opposed to 2,095 performed in the haemostasis laboratory in the same period. According to the American Medical Association criteria only 48% of the requests could be warranted, and abnormal findings appeared in only 10% of them. CONCLUSIONS: The cost per isolated parameter is low, but it increases greatly when compared with the benefit that it reports to the patient because, as those biological tests indirectly measure the concentration of clotting factors, they are subjected to error when performed by non-specialized personnel; on the other hand, the most valuable information for detecting haemorrhagic troubles comes from the patient's history. The economical burden in the month studied amounted to 985,879 PTA; one year later, the same laboratory, in the same month, had a 50% increase of studies. PMID- 1440092 TI - [Antithrombin III: its prognostic value in acute pancreatitis]. AB - PURPOSE: Antithrombin III (AT-III) activity was studied in relation to the seriousness of a series of patients with acute pancreatitis (AP). The aim of this study was to determine whether AT-III can be a prognostic factor for early detection of negative evolution on these patients. MATERIAL AND METHODS: AT-III was determined on days 1, 3, 5, 7, 10, 15 and 21 after admission and weekly until discharge in 28 consecutive patients with AP, admitted in our hospital during a period of six months. The patients were 13 males and 15 females, with a mean age of 57 years (range 32 to 82). Fifteen AP were serious and 13 were not. RESULTS: AT-III levels under 80% of activity were found up to the 10th day in serious AP, turning back to normality from this day. In nonserious AP, AT-III remained within normal levels. This different evolution between both kinds of AP was statistically significant (p less than 0.05) during the first seven days, and became more evident in patients with fatal evolution (p less than 0.001). After grouping the lower levels of AT-III observed during the first 48 hours with those detected at the end of the first week, and introducing a cut off value of AT-III under 70% of activity, serious and nonserious AP presented predictive indexes of 67 and 70% respectively. Every deceased patients had, at admission and at the end of the first week, average levels of AT-III under 70%. CONCLUSION: We conclude that determination of AT-III levels is a good prognostic factor to differentiate between serious and nonserious AP, especially during the first week of illness. PMID- 1440093 TI - [Progression to AIDS among HIV-seropositive hemophiliacs]. AB - PURPOSE: To assess the incidence of AIDS, along with its origin and mortality rate, in a group of sero-positive haemophiliacs with long follow-up. MATERIAL AND METHODS: The progression into AIDS in 94 HIV-seropositive haemophiliacs (88 with haemophilia A and 6 with haemophilia B) followed since 1986 has been analyzed. The mean age was 19 years and 64% of the patients had severe haemophilia. All of them had been previously treated with non virus-inactivated factor concentrates. Was detected HIV antigen in 13 of them and 32 were treated with zidovudine. Actuarial analysis started from seroconversion date or from the first positive result and the average observation time was 90 months (5-97). RESULTS: Sixteen patients developed AIDS, resulting in an eight-years accumulative actuarial indice of about 24%. AIDS incidence was lower (p less than 0.0001) in haemophilia A (21%) than in haemophilia B (67%). The eight-years progression rate to AIDS showed a significant dependence on patient age, it being higher in patients aged greater than 30 (77%) than in those aged 15-30 (30%) and less than 15 (9%). Patients who presented CD4+ counts lower than 0.5 x 10(9)/L or CD4/CD8 ratios lower than 0.5 at the beginning of the observation period had a greater 8-year AIDS incidence (63% and 57% respectively) than the remaining patients (16% and 12%). At AIDS diagnosis, all patients had CD4+ lymphocyte counts lower than 0.2 x 10(9)/L, two had detectable HIV antigenaemia and six had been previously treated with zidovudine. The cause of AIDS was an opportunistic infection in all the cases namely, P. carinii pneumonia and candidiasis, but no secondary neoplasia was registered. Nineteen patients died during the follow-up, 12 because of AIDS and 7 because of other reasons unrelated to HIV-infection. CONCLUSION: Our results suggest that 25% of the haemophiliacs will develop AIDS eight years after seroconversion, and a decreasing incidence is not observed. Lower progression rate to AIDS in children than in adults is confirmed. PMID- 1440094 TI - [Utility of the examination of plasma-cell morphology in the study of multiple myeloma]. AB - PURPOSE: To assess the classification of Greipp et al in a group of multiple myeloma (MM) patients, in an attempt to correlate the morphological patterns with the clinico-biological features of the disease. MATERIAL AND METHODS: Bone marrow aspirates from 135 patients with multiple myeloma were examined by two different observers. RESULTS: Full accordance existed in 122 cases (90%). The four morphological MM subgroup distribution was: mature, 38%; intermediate, 30%; immature, 18%, and plasmoblastic, 14%. The analysis of the M component types with regard to morphology showed increased IgA cases within the intermediate (40%) and immature (48%) MM (p = 0.01), and Bence-Jones cases within the plasmoblastic MM (32%). On the contrary, no differences were found with regard to the clinical stage, although none of the plasmoblastic MM was in stage I. The incidence of renal insufficiency and of high bone-marrow infiltration progressively increased from mature to plasmoblastic MM, the difference between the extreme morphological groups being significant. The incidence of hypercalcaemia and lower paraprotein rates was higher in plasmoblastic myeloma, with significant difference with respect to mature myeloma (p = 0.05). The median survival was longer in intermediate (27.8 months) and mature (22.5 months) myelomas than in plasmoblastic (17.9 months) and immature (13.6 months) myelomas. After grouping the mature forms (intermediate plus mature) and the immature ones (plasmoblastic plus immature) the survival differences approached statistical significance (p = 0.07). CONCLUSIONS: This study suggests that the morphological examination of plasma cells should be included in the prognostic criteria of multiple myeloma. PMID- 1440095 TI - [Initial dosage of vancomycin in neutropenic hematologic patients]. AB - PURPOSE: To evaluate the percentage of neutropenic patients who reach the therapeutic threshold when vancomycin is given at standard initial doses of 500 mg/6 hr, and to assess the creatinine clearance and body vancomycin clearance in such patients. MATERIAL AND METHODS: The study was performed on 37 haematological patients with normal renal function. They received intravenous vancomycin at an initial 500 mg/6 hr doses. The plasma concentration of the drug was assessed 48 72 hr later, pharmacokinetic parameters being calculated. Creatinine clearance was estimated by two different methods. RESULTS: The concentration attained was beyond the therapeutic threshold in 100% of the patients. The correlations between vancomycin and creatinine clearance were r = 0.42 and r = 0.47 when the Cockroft-Gault's and the Jellife's methods, respectively, were used. Administration of vancomycin at initial doses of 500 mg/6 hr renders a very high percentage of patients with plasma concentration of the drug beyond the therapeutic margin. CONCLUSIONS: 1) The poor correlation between creatinine and vancomycin clearance in the patients with normal renal function does not allow using nomograms based on such values for estimation of the initial doses. 2) The estimation of initial doses based on the patient's weight (20-25 mg/kg) may render a higher percentage of patients with therapeutic concentrations from the beginning of treatment. The maintenance doses can be adjusted at 48-72 hr, after measuring the plasma concentrations. 3) Therefore, it seems advisable to perform further clinical assays on different groups in order to verify an increase of the drug's efficacy with no higher toxicity when the initial vancomycin doses is adjusted according to the patient's weight, as recommended here. PMID- 1440096 TI - [Superoxide dismutase (SOD) and aging]. AB - The rates of SOD in the Spanish population have been studied in an attempt to correlate them with aging. The study was comprised of 94 healthy blood donors with ages between 58 and 65 years. The findings were compared with those of 2,297 healthy normal subjects previously reported. The method of Miami and Yoshikawa was judged the technique of choice for a population study. The SOD levels found were 4.04 +/- 0.83 U/mL. Individuals from rural areas had values of 3.09 +/- 1.31 (p = 0.01), whereas subjects from urban environment showed values of 4.20 +/- 0.97 (p: ns). These figures, in the Spanish population as a whole, were 4.16 +/- 0.89, 3.81 +/- 0.9 and 4.22 +/- 0.97, respectively. The SOD rates in blood donors aged 58-65 years from the rural environment are significantly lower than those os their urban counterparts. The levels in this age-group are significantly lower than those of the general population. These findings suggest that increased SOD activity in the urban areas could result from a better protective mechanism with regard to higher concentrations of superoxide radicals which other would achieve toxic effects. PMID- 1440097 TI - [Severe hemolytic anemia caused by anti-AB in renal transplantation with minor ABO incompatibility]. AB - A 54 year-old woman subjected to renal transplant with minor ABO incompatibility developed clinically severe anti-AB haemolytic anaemia. On the 13th day after transplantation the patient had: haemoglobin, 7.5 g/dL, unconjugated bilirubin, 393 mumol/L (23 mg/dL), and undetectable haptoglobin levels. Positive direct antihuman globulin test was found, and an IgG antibody capable of binding complement and with anti-AB specificity was found upon studying the eluate. Immunosuppressive therapy improved the clinical picture, although antibodies could still be detected one month later. Clinically significant immune haemolysis after renal transplantation appears in about 10-15% of those cases having antibodies against the host's antigens. The peak red-cell destruction is seen one to two weeks after grafting, and haemolytic signs may last for about three weeks. Although self-limited, this condition may achieve high severity. The duration and severity of haemolysis depend upon the density of antigen sites on the surface of the host's red-cells, his secretor trait, the presence or absence of complement activation and the immunosuppressive therapy including cyclosporin. Several cases of anti-A and anti-B specificity have been reported, but anti-AB specificity had not been previously found; this fact is probably related to the scarce interest paid to its search thus far. PMID- 1440098 TI - [Kikuchi-Fujimoto necrotizing lymphadenitis associated with brucellosis]. AB - A 22 year-old woman was referred to the hospital for treatment after being diagnosed of Hodgkin's disease, established by lymph node biopsy. She complained of fever and sweats, and no lymph node enlargement or visceromegaly could be appreciated. Kikuchi's necrotising lymphadenitis was diagnosed after reviewing the lymph node specimen. The microbiological and serologic tests performed showed the existence of brucellosis. The clinical symptoms easily disappeared after treatment with streptomycin and doxycycline and she has been well, with no other symptoms or lymph node enlargement, after one year of follow-up. Kikuchi's disease is usually associated with different infections, although it had never been reported in association with brucellosis. This picture can easily be mistaken as malignant lymphoma or Hodgkin's disease. PMID- 1440099 TI - [Hodgkin's disease. Recurrence after 16 years' continuous remission]. PMID- 1440100 TI - [Chronic myeloid leukemia with progression to polycythemia vera]. PMID- 1440101 TI - [Iron deficiency and catecholamines in women]. PMID- 1440102 TI - [Late post-transfusional hemolysis caused by anti-Kidd-b]. PMID- 1440103 TI - [Meningeal myelomatosis]. PMID- 1440104 TI - [Autoantibodies in hemophilia: consequence of HIV-1 infection and/or cofactors in the development of the infection?]. PMID- 1440105 TI - Professional and family collaboration in case management: a hospital-based replication of a community-based study. AB - This paper presents the results of research on a program that trains family members to serve as case managers for their elderly relatives. The effectiveness of the training program was evaluated using a randomized experimental design. Data were collected in an urban hospital setting about two groups of elderly patients: those with dementia and those needing hemodialysis. Family members of both types of patients were assigned randomly to an experimental group, which received systematic training in performing case management activities, or to a control group, which received only the services ordinarily provided by the hospital social work department. Post-test comparisons revealed that the experimental group family members performed significantly more case management tasks on behalf of their elderly relatives than did family members in the control group. Although trained family members assumed more responsibility for case management, there was no increase in the level of their subjective or objective caregiving burden. Implications for social work practice are presented. PMID- 1440106 TI - Improving access to health care: case management for vulnerable children. AB - Health care providers are being confronted by a change in childhood morbidity from primarily physical problems to complex problems rooted in the social, family, and environmental conditions that accompany persistent urban poverty. The clustering of multiple problems in one family necessitates redefining preventive and treatment strategies. Yet the lack of coordination among federal, state and local service programs often exacerbates the vulnerability of these beleaguered children and families. Therapeutic case management is a powerful service coordination strategy for increasing access and improving the health of vulnerable children. An ongoing evaluation of one case management model at the Center for the Vulnerable Child at Children's Hospital in Oakland, California is described in this article. Process evaluation data show this model to be effective in improving comprehensiveness and continuity of care among participating families. PMID- 1440107 TI - Reducing older patients' reliance on the emergency department. AB - Older adults tend to avoid mental health services and rely on hospital emergency departments for medicalization of these conditions. An intervention was designed for use in emergency departments to refer older adult patients with mental and social health problems to appropriate services within the hospital and community. Most of the patients in the study used the services to which they were referred; further, the intervention was found to decrease repeat utilization of the emergency department. Social work practice and policy implications of the findings are also discussed. PMID- 1440108 TI - Hospitals and school districts: creating a partnership for child protection services. AB - This article reports the initiation of a joint hospital-school district child protection committee in an urban setting of socio-economic blight. The committee provided a structure for consultation about troubling, complex situations of school children at high risk for physical and sexual abuse and medical neglect. PMID- 1440109 TI - Patient psychoeducation: the therapeutic use of knowledge for the mentally ill. AB - Psychoeducation has been used successfully with families of patients with psychiatric illness for over the past two decades. Modifying this model for use with mentally ill patients has demonstrated to both patients and staff the positive impact that knowledge can have on patients' functioning and attitudes. The model described has three objectives: (1) to impart information about psychiatric illness, medication and treatment regimens as a way of increasing patients' understanding, (2) to provide a forum which facilitates the integration of this information through group discussions with other patients and (3) to teach and model some specific management skills for patients as they deal with their illnesses. PMID- 1440110 TI - Treating women incest survivors: a bridge between "cumulative trauma" and "post traumatic stress". AB - While the concept of traumatic stress plays an intrinsic part in the diagnosis and treatment of adult incest survivors, the developmental framework within which the victimization has occurred may be overlooked. This paper presents a treatment model that integrates theories of post-traumatic stress and early environmental trauma. A profile of women incest survivors is given and an overview of treatment strategies utilizing the above theories is discussed. PMID- 1440111 TI - AIDS and social work: a decade later. PMID- 1440112 TI - Working with denial: a critical aspect in AIDS risk intervention. AB - Denial as a defense against anxiety can block the effectiveness of education and confrontation in work with clients manifesting AIDS risk behavior. The mechanism of denial is explored with reference to its role in supporting sexual acting out of unconscious conflicts. Clinical illustrations demonstrate the importance of work with denial as a prestage to effective AIDS risk intervention. Work with heterosexual and homosexual men and women is cited. PMID- 1440113 TI - Obstacles to effective case management with AIDS patients: the clinician's perspective. AB - A social work clinician filled the role of case manager with multiple functions of discharge planner, client advocate, counsellor and educator in her work with a young male AIDS patient and his family. Material from this case is used to illustrate seven problem areas identified as obstacles to effective case management: (1) The stigma of AIDS and homosexuality (2) Lack of adequate family support (3) Impact of AIDS dementia (4) Ethical dilemmas in discharge planning (5) Conflicts in the advocacy process (6) Lack of adequate resources and (7) Countertransference issues. Clinical observations are integrated with the existing social work literature which focuses on providing services to AIDS patients. PMID- 1440114 TI - Latinos and HIV disease: issues, practice and policy implications. AB - This paper examines critical issues faced by Latino PWAs and offers suggestions for meeting the needs for community support and care of Latino PWAs and their families. As HIV disease is shifting increasingly to minority communities, social workers need to consider new approaches to developing community care. Drawing on the strengths and informal support networks of the Latino community, the authors suggest ways in which these strengths can form the basis of service strategies that will effectively meet the needs of Latino PWAs. PMID- 1440115 TI - Development of an instrument to measure volunteer's motivation in working with people with AIDS. AB - A scale, "Attitude Towards Volunteer Motivation," was developed to measure motivation of volunteers who work with people with AIDS (PWAs). Fifty five questions were initially determined to have content validity. They were then administered to a random sample of youth services volunteers (n = 150) and members of an AIDS volunteer organization (n = 247). Results of factor analysis produced five subscales. Reliability of the constructed scale was established. It was correlated with a theoretically related scale to establish construct validity. Results of this initial research are promising and suggest further testing of the instrument. PMID- 1440116 TI - Hospital boarder babies and their families: an exploratory study. AB - Data were abstracted from the medical and social work charts of 20 newborns who were classified as boarder babies and their mothers (N = 18) to identify bio psycho-social factors associated with boarding. The findings show that the mothers whose newborns remained in the hospital as boarders were usually drug users, had other children in out-of-home placement, and over half are periodically homeless. Most of these mothers also lacked informal social support. The major health problems of infants were prematurity and associated infections. The total number of infant boarding days was 195 for a total of $117,000 in unreimbursed costs to the hospital. Practice and program implications and directions for future research are discussed. PMID- 1440117 TI - Lessons in caring: how social work integrates psychosocial values into family practice residency training in Israel. AB - This paper presents a model of social work consultation to family practice physicians in two locations in Israel, a kibbutz and an urban family practice medical center. When residents learned to identify and understand how psychosocial factors interact to enhance or impair the physician-patient encounter, they experienced improved quality in their relationships and practice. Physicians learned how the identification of needs can enhance their comfort and effectiveness with patients and how an appropriately made referral to a mental health professional is seen as an act of caring. PMID- 1440118 TI - Efficacy of chlorhexidine swabbing in oral health care for people with severe disabilities. AB - Chlorhexidine is effective when used as an oral rinse, but many disabled people cannot use such a protocol. A double-blind cross-over study tested the efficacy of applying chlorhexidine with a sponge-swab, in a sample of 76 severely disabled adults, drawn from diverse rehabilitation settings. Two randomly assigned groups applied 10 mL 0.12% chlorhexidine gluconate (Peridex, Procter & Gamble) or 10 mL placebo, using a "Toothette" (Halbrand) once daily, 5 times per week for 10 weeks. All subjects received 10 mL 0.05% NaF, applied similarly but separately from the test/placebo agent. Pre- and post-trial measures included perceived level of function and oral status, that is, DMFS, plaque, calculus, pocket depth, and tooth stain. The protocol received high levels of compliance and acceptance. Compared with placebo, swabbing with chlorhexidine resulted in consistent, and, in part, significant improvements in plaque, gingivitis, and periodontal pocket depth. Side effects of chlorhexidine, that is, tooth stain and calculus, were relatively minor. Perceived improvements in dental health were associated with improved physical health, appearance, and mouth odor. The results indicate that chlorhexidine swabbing is a useful oral disease preventive protocol for persons with disability. PMID- 1440119 TI - Dental care in psychiatric hospitals in The Netherlands. AB - This study determined the method of organization of dental care in psychiatric hospitals in the Netherlands, investigated patients' dental problems, and examined hospital nurses' role in prevention and diagnosis of dental problems. A bad oral condition, bad oral hygiene, and badly fitting dentures were the problems most frequently noticed. If the patients neglected brushing their teeth, 70% of the nurses interviewed never took over, 20% sometimes did, and 8% always did. It was concluded that, although most psychiatric hospitals had their own dental clinic or alternative dental facilities, adequate dental care had not yet been realized everywhere. The role of the nursing staff in preventing and diagnosing dental disease can further be strengthened. PMID- 1440120 TI - Attitudes of older versus younger adults toward dentistry and dentists. AB - A total of 416 adults were interviewed by telephone to gauge their attitudes toward dentistry and dentists. Attitudes of those age 55 and older were compared with those younger than age 55. It was found that 72% of those 55 and older had not visited a dentist in the previous 2 years because they felt it was not necessary; 38.5% of respondents younger than 55 gave this reason. Only 15% of those 55 and older reported that high costs kept them away from the dentist. PMID- 1440121 TI - Effect of medical status on dental procedure time. AB - The purpose of this study was to determine if treatment of medically compromised patients requires more time than that of healthy patients. The time taken to complete diagnostic and manipulative procedures was studied and compared for both groups. After an evaluation of 160 procedures on 108 patients, it was determined that no differences existed in the time taken to complete technical procedures between the two groups. However, the diagnostic and evaluation phase for moderately to severely compromised patients required twice as much time as that of healthy individuals. PMID- 1440122 TI - Sociodemographics of homebound people in Kentucky. AB - In this report, selected results are presented from the 1987 Kentucky Oral Health Survey, which acquired statewide data on the oral health status and practices of the noninstitutionalized population of Kentucky. In the 1987 epidemiological survey, information about persons who were homebound was also gathered through telephone and in-person interviews. The results of that survey provided a relatively accurate estimate of the number of persons homebound in the state of Kentucky. Although the majority of this population was older than age 60, almost 21% were between the ages of 35 and 59. Household income for persons who are homebound and the amount of money spent on dental care is significantly less than in households not reporting the presence of a person who is homebound. These findings provide baseline data for dentists and health planners interested in serving this population. Also, this data is pertinent to the formation of health policies to create accessible, affordable care for this growing segment of the population. PMID- 1440123 TI - Suspected inappropriate secretion of antidiuretic hormone in a male with mental retardation. AB - The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a disorder in which a sustained release of antidiuretic hormone occurs because of certain diseases, pharmacological agents, or trauma. Fluid volume expands with a resultant hyponatremia which, depending on the degree, may be asymptomatic or result in death. This case report describes a 38-year-old male in whom SIADH was strongly suspected secondary to Tegretol therapy to control a seizure disorder. Medical consultation is imperative for these patients before administering a fluid challenge during general anesthesia. PMID- 1440124 TI - A modified light-cured denture identification technique. AB - Removable dental prostheses are lost frequently or stolen in nursing homes. Dental personnel may not be routinely available to many nursing home residents to place identification labels, and nursing staff members are not trained to use traditional denture marking techniques. This article describes a modified simple marking technique that may be used by either dental personnel or nursing staff members. Using ordinary sandpaper, lead pencil or ball pen, art and craft brush, direct light, and a mono-poly sealer of 1 part heat-cured clear methylmethacrylate powder mixed with 10 parts of autopolymerizing clear orthodontic methylmethacrylate liquid, 26 dentures were labeled for 19 nursing home residents. The technique was quick, cheap, easily applied, nonirritating to mouth tissues, and permanent. PMID- 1440125 TI - Perioperative hemodynamic changes in ischemic heart disease patients undergoing dental treatment. AB - Twenty patients with stable ischemic heart disease in functional capacity Class II-IV underwent dental treatment. Scaling was performed in seven patients without local anesthesia. In the remaining 13 patients, pain control for restoration placement was obtained by local anesthesia: in seven patients, the anesthetics contained epinephrine, while in six this drug was omitted. Heart rate, blood pressure, and electrocardiograph were continuously monitored during the dental session. All patients had elevated systolic blood pressure and rate pressure product during treatment. In the patients who received plain local anesthetics only, the elevation in systolic blood and rate pressures was, however, significantly lower than the ischemic threshold. Arrhythmia or ST segment depression of > or = 1 millimeter were not recorded in any of the subjects. In severely compromised ischemic heart disease patients undergoing routine dental procedures of limited chair time, plain local anesthesia seems to be the preferred analgesic modality. PMID- 1440126 TI - The lack of efficacy of a foam brush in maintaining gingival health: a controlled study. AB - Foam brushes have been used in the oral care of hospitalized patients for many years. However, no controlled study of their efficacy has been conducted. A randomized crossover study, comparing the effectiveness of a foam brush with that of a toothbrush, was carried out. The gingival condition and presence of plaque in the mouths of 29 volunteers were followed. It was shown that a toothbrush was more effective in controlling plaque levels and gingivitis. PMID- 1440127 TI - Pharmacotherapy in the geriatric population. AB - The geriatric population constitutes the largest group of consumers of medications in this country. Changes in the pharmacokinetic response to medications of this population are less predictable than in younger age groups, thereby resulting in adverse reactions and drug interactions in multidrug users. Dentists need to be aware of these changes as well as alterations in therapeutic responses to the medications most commonly used in dental treatment: sedatives, local anesthetics, analgesics, and antibiotics. PMID- 1440128 TI - A dentist's social responsibility to diagnose elder abuse. AB - Because of the high prevalence of dental disease and consequent need for dental care in the elderly, dentists are in frequent contact with the elderly, thus providing an opportunity for realizing their social obligation to become more involved in diagnosing and reducing elder abuse. Current estimates of the incidence of elder abuse in the US indicate that nearly 10% of the elderly population is affected, and this incidence rate is steadily increasing. Problems of vague definitions regarding abuse, elusiveness of the problem, and limited interest on the part of health care professionals may have deterred dentists from more involvement in the past. Apathy, tunnel vision, and vested interests of dental professionals may also contribute to the poor oral health of the elderly and consequently decrease the elders' quality of life. However, by developing a clear understanding of possible etiologies and by knowing physical and behavioral indicators of abuse, dentists can better fulfill their moral and social obligations and greatly reduce the incidence of elder abuse. PMID- 1440129 TI - Effects of hyposalivatory medications on saliva flow rates and dental caries in adults aged 65 and older. AB - Institutionalized adults aged 65 or older often receive medications that have been associated with decreased saliva flow. Flow rates depressed by hyposalivatory medications are thought to increase susceptibility to dental caries. In this study, a cross-sectional comparison was made of stimulated whole saliva rates and coronal and root caries prevalence in a group of older adults, in a long-term care facility, taking hyposalivatory medications vs. a control group. No significant differences were found between the two groups in masticatory or gustatory stimulated flow rates or in mean decayed coronal or root surfaces. PMID- 1440130 TI - The use of vacuum-molded polyvinyl acetate-polyethylene copolymer (PVAC.PE) for a handicapped patient. AB - This paper provides a survey of recent literature on the use of mouth sticks for patients who have little or no use of their limbs. Criteria for mouth stick design, types of appliances, and the fabrication of such devices are described. Details are given of a case of a young child with arthrogryposis multiplex congenita, in whom a novel approach was used to allow the safe intra-oral retention of writing implements. PMID- 1440131 TI - Erythema multiforme: a literature review and case report. AB - Erythema multiforme is a florid mucocutaneous disease characterized by oral, cutaneous, and ocular manifestations. The cutaneous lesions are pathognomonic because of their unique "target-like" appearance. A severe form of EM has been termed "Stevens-Johnson Syndrome". Although the etiology of EM is unknown, much of the research suggests an immunological association with HSV. The diagnosis of EM is based on signs and symptoms, and a differential diagnosis should include other ulcerative, mucocutaneous diseases, such as erosive lichen planus, pemphigus, varicella zoster, ANUG, TEN, aphthous stomatitis, and primary HSV. Therapeutic measures are palliative, including a soft bland diet, topical anesthetics, and corticosteroids. A case of EM is described which underscores the appearance of the disease and its clinical course. PMID- 1440132 TI - Surgical management of a patient with cleidocranial dysplasia: a case report. AB - Cleidocranial dysplasia is associated with the formation of many supernumerary teeth which usually fail to erupt. In later life, cysts may form around the embedded teeth. The following report describes the management of such a case with a method which promotes satisfactory prosthodontic rehabilitation. PMID- 1440133 TI - Streptococcus mutans, lactobacilli, and caries experience in older adults. AB - This study investigated salivary levels of Streptococcus mutans, lactobacilli, and caries experience in a random sample of 448 black and 362 white older dentate adults living in North Carolina. Significant proportions of the participants had stimulated salivary flow rates less than 1.0 mL/min, salivary buffering capacity less than 4.0, S. mutans levels of 10(5) cfu/mL or more in stimulated whole saliva, or lactobacilli levels of 10(5) cfu/mL or more. Each of these factor levels could be considered, on a clinical basis, to increase caries risk. In general, people with higher levels of S. mutans or lactobacilli had more untreated coronal and root caries, but not greater total caries experience. PMID- 1440134 TI - The role of salivary function on oropharyngeal colonization. AB - Aspiration of oropharyngeal flora is the most common route of acquiring Gram negative pneumonia, a major nosocomial infection. Epidemiologic studies indicate that the elderly are at increased risk for developing these life-threatening pneumonias. The primary objective of this study was to determine the effects of salivary oral defenses against Gram-negative colonization. The study population consisted of 41 male outpatients, age 70 and older, seen at the Denver VAMC. The group included subjects with both diminished and normal salivary flow. Each subject answered a questionnaire regarding overall health, medication use, and symptoms of salivary dysfunction. We then collected whole saliva, unstimulated and stimulated parotid saliva, and performed a throat swab on each patient. For each throat culture, analysis was done to identify Gram-negative bacteria. Flow rates between colonized (n = 6) and noncolonized subjects (n = 34) were compared. While there were no significant differences in the flow rates between the two groups, a trend was noticed in that flow rates were lower for all three flow measures in the colonized group (whole, 22% decrease; unstimulated, 22% decrease; and stimulated, 28% decrease). These preliminary findings suggest that subjects with diminished salivary flow may possibly be at increased risk for oropharyngeal Gram-negative colonization. Research on the role that saliva plays in oropharyngeal bacterial colonization is continuing. PMID- 1440135 TI - A national survey of medical risk assessment instruction in general practice residency programs (Part I). AB - Formal and structured training in medical risk assessment (MRA) has been a requirement in general practice residency (GPR) programs since their inception in 1972. Institutions offering GPR programs frequently differ in the levels and types of available resources necessary to implement this training. Program directors have expressed significant concerns that this training is difficult to provide, especially in the area of physical examination. The literature has not yet established how or if programs have organized their curricula to conform to accreditation standards in MRA established by the American Dental Association's Commission on Dental Accreditation. The purpose of this study was to conduct a nationwide survey of all GPR programs to identify program characteristics and resources, didactic and clinical educational methods, and perceived achievement of ADA Standard Fourteen for MRA training. Recommendations for further research are also given. Results will be reported in this paper, the paper following in this issue, and an additional paper to be published in a forthcoming issue. PMID- 1440136 TI - A national survey of medical risk assessment instruction in general practice residency programs (Part II). AB - This is the second part of a three-part series reporting a national survey of general practice residency directors and their evaluation of the medical risk assessment (MRA) instruction curriculum in their programs. The purpose of Part II is to evaluate the degree of success of the implementation of the ADA Commission on Accreditation's standard for MRA programs. Acceptable levels of achievement were attained in most areas of basic and intermediate-level skills. However, approximately one-third to one-half of general practice residency directors report that they are not achieving the standard for some intermediate or advanced assessment skills. When various instructor categories were compared, physicians scored significantly higher than oral and maxillofacial surgeons or other dentists in their ability to achieve acceptable outcomes in MRA instruction. The results of this survey, coupled with available literature concerning medical risk assessment instruction, support that changes in the undergraduate curriculum, a mandatory additional year of training, or modification of defined goals and outcomes should be considered. PMID- 1440137 TI - Metastatic colon carcinoma to oral soft tissues. AB - Metastatic tumors to the oral cavity are uncommon. Most of these cases involve the mandible or the maxilla. Rarely, metastasis occurs to the oral soft tissues from a distant primary tumor. The lung and breast are the most common primary sites. It is extremely rare to have an oral soft-tissue metastasis from a carcinoma of the colon. A case of primary adenocarcinoma of the colon with metastasis to the soft tissues of the mouth is described. Three similar case reports are reviewed. A metastatic lesion to the oral cavity could be the first indication of the presence of a primary tumor. PMID- 1440138 TI - Lip-chewing: another treatment option. PMID- 1440139 TI - Dietary and salivary factors associated with root caries. AB - In this pilot study, dietary habits, microbial factors, and salivary factors in 20 older adults who had active decay on root surfaces were compared with those of 20 adults who had inactive or no root caries. In this case-control study, the groups were matched by sex and were of similar age. Subjects using medications known to induce dry mouth were excluded. Subjects completed a nutrition interview and a four-day food diary. Stimulated whole saliva flow rate, buffering capacity, levels of salivary lactobacilli with use of the Dentocult method, and S. mutans cultured on MSB agar were determined. The root caries group had a greater mean number of eating occasions per day (6.1 vs. 4.6), more frequent exposures to fermentable carbohydrates (5.8 vs. 4.2), and higher average daily sugars intake (133 g/day vs. 105 g/day) than the control group. Root caries subjects had significantly higher lactobacilli counts and less salivary buffering capacity. Within the root caries group, significant correlations were found with Root Caries Index and lactobacilli (r = 0.56) and S. mutans counts (rs = 0.50). These results show that frequent intake of simple sugars, high lactobacilli counts, and low saliva buffering capacity may be risk factors associated with root caries in older adults. PMID- 1440140 TI - Therapeutic laparoscopy in general surgery. PMID- 1440141 TI - Inflammatory bowel disease. PMID- 1440142 TI - Ureterorenoscopy. PMID- 1440143 TI - An approach to the management of penile cancer. PMID- 1440144 TI - Rectal prolapse and other pelvic floor abnormalities. PMID- 1440145 TI - Controversies in surgical management of asymptomatic peripheral vascular disease. PMID- 1440146 TI - Reconstruction of deep venous valves of the lower extremity. PMID- 1440147 TI - Nesidioblastosis: still an enigma. PMID- 1440148 TI - Enteral nutrition in the intensive care unit. PMID- 1440149 TI - Renal hyperparathyroidism. AB - The indications for surgical treatment of renal HPT in patients with chronic endstage renal failure are symptomatic disease or failed medical management. The indications for patients who have had a kidney transplant are symptomatic disease and persistent hypercalcemia. It should be noted, however, that the current approach favored in the literature in asymptomatic, mild post-transplant hyperparathyroidism is conservative. Total parathyroidectomy with autotransplantation is the most popular surgical method reported. I have done subtotal parathyroidectomy and reserved total parathyroidectomy for selected patients. My recurrence rate is comparable to that reported. The actual survival rate in our two groups of patients was 58 percent for the dialysis patients and 79 percent for the transplant patients. The actuarial survival rates at 1, 5, and 10 years in the two groups were 95 and 92 percent; 59 and 67 percent; and 32 and 67 percent. The use of diphosphonates and medical rather than surgical control needs further study, as do the long-term effects of conservative treatment of asymptomatic post-transplant hyperparathyroidism. PMID- 1440150 TI - Oncogenes, growth factors, and prognostic indicators in colorectal cancer. PMID- 1440151 TI - An appraisal of the gastroesophageal antireflux barrier and the lower esophageal sphincter. PMID- 1440152 TI - Fluid and electrolyte management in the pediatric surgical patient. AB - The following is a quick guide to the perioperative fluid program discussed 1. Always assess the state of fluid repletion in any patient presenting for surgical management (Note: This does not necessarily mean operative management). 2. If the patient is hypovolemic or if there is the possibility of hypovolemia and you are uncertain, restore volumes equal to 25% of the patient's blood volume with a fluid push made up of an osmotically active electrolyte solution modified for the additional requirements of red cell carrying capacity or clotting factors. If this results in a urine output and correction of hypoperfusion or hypotension, maintain an increased fluid administration program until a stable urine output and good perfusion are achieved. If the patient is normovolemic at the time of presentation, particularly if the patient is having an elective operative procedure and does not have an intravenous line in place, calculate the insensible losses that will occur during the time of fluid restriction before surgery and correct at least 50% of these during the operative procedure. 3. Develop the postoperative fluid program as a combination of 24-hour insensible loss replacement (maintenance fluid), restoration of measured losses, and an estimate (guess) as to the volume requirements for third-space fluid shifts. Restore blood losses if appropriate or administer additional volumes of balanced electrolyte solution at a 3-to-1 ratio to replace measured blood loss. 4. Total the insensible loss measurement, the measured losses, and the estimate of third space requirement and divide this volume by 24 to get an initial hourly fluid administration rate. 5. Select the most osmotically active fluid that you intend to use and administer it first at the calculated rate. Carefully monitor the patient's urine output. 6. Increase or decrease the fluid administration rate to bring the hourly urine output within the guidelines for the appropriate hourly urine output (milliliters) for the particular patient based on size (kilograms). 7. When the urine output falls within the appropriate range, maintain that rate of fluid administration, and recalculate the volumes required because of insensible loss, measured loss, and third-space shifts by subtracting the amount of fluid already administered from the volume that will be required in the remainder of the 24 hours; this will yield the volumes of additional maintenance, measured loss, and third-space fluids that will make up the remainder of the fluids needed for the 24 hours.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1440153 TI - Update on anesthesia management for infants and children. AB - This review aims at providing the pediatric surgeon with an update on the most important issues in pediatric anesthesia and the changes that have taken place over the last few years. Many practices, entrenched in tradition, are being modified in the light of research that has provided new knowledge, drugs, and techniques. Pediatric anesthesia requires dedication, a sense of anticipation, meticulous attention to detail, and an individual who derives enormous satisfaction from the pleasure to be had from dealing with these small patients and their families. PMID- 1440154 TI - Surgical management of children with hemoglobinopathies. AB - Sickle hemoglobinopathies include sickle cell disease, sickle-C disease, and sickle-beta thalassemia. Patients with these disorders commonly suffer a multitude of destructive events to vital organs, especially to the central nervous system, the spleen, the kidney, the lung, and the heart as a result of microvascular plugging by the sickled erythrocytes. Thoughtful preparation for anesthesia and operation, especially when directed by experienced individuals, can greatly reduce the hazard of inducing the sickle crises that formerly plagued individuals with sickle hemoglobinopathies who faced major operations under general anesthesia. The patient must be free of any acute illness, especially one involving the respiratory system. Adequate hydration preoperatively combined with avoiding perioperative hypoxia, hypothermia, and acidosis, the triggers for sickling, will go far toward avoiding sickle-induced complications. Modern transfusion therapy, consisting of multiple small transfusions of Hb A erythrocytes administered over several weeks prior to the operation, not only corrects the chronic anemia but suppresses erythropoiesis of cells containing Hb S in the patient's bone marrow and leaves him or her with a majority of cells containing Hb A. This provides a safety net in case a sickle-inducing insult occurs despite the best efforts to avoid one. Individuals with sickle hemoglobinopathies may require any of the operations common to all children, for example, herniorrhaphy, appendectomy, tonsillectomy, and circumcision, but a significant number will develop calcium bilirubinate cholelithiasis and possibly cholecystitis as a result of the continual increased load of bile salts resulting from the shortened lifespan of the cells containing Hb S. Also, although most individuals with Hb S will gradually suffer splenic infarction by late childhood, a significant number of infants will experience acute splenic sequestration crisis, a life-threatening entity, the recurrence of which is prevented by splenectomy. Several publications have demonstrated that such surgical procedures can be performed in large numbers of patients with sickle hemoglobinopathies without deaths and with minimal morbidity. PMID- 1440155 TI - Metabolism and nutritional frontiers in pediatric surgical patients. AB - The successful treatment of pediatric surgical disease requires an understanding of the acute metabolic stress response. Poor clinical outcome can result when the metabolic demands of acute injury exceed the ability of endogenous host mechanisms to compensate. Appropriate exogenous supplementation may provide the metabolic and nutritional support crucial to recovery. As knowledge in this area grows, more effective treatment strategies are evolving. The potential for further advances, especially in the infant critical care population, offers the hope for substantial progress in the near future. PMID- 1440156 TI - Vascular access techniques and devices in the pediatric patient. AB - Vascular access is a sine qua non in the management of pediatric surgical patients. The indications, as well as the number of available access routes, types of devices, and their use, have expanded over the last two decades. This article is an overview intended to allow the surgeon to match the safest and most effective access to the child's therapeutic needs. It also contains descriptions of sites for percutaneous and cut-down vascular access in children, as well as the author's personal approach to central venous access. Vascular access in children requires skill, time, patience, and the appropriate equipment. Fortunately, with attention to detail, most complications can be avoided. PMID- 1440157 TI - Gastrostomy techniques and devices. AB - Gastrostomies play an important role in the management of a wide variety of surgical and nonsurgical conditions of childhood. Many techniques and gastrostomy devices are available. In our experience, percutaneous endoscopic gastrostomy has proved safe and effective, and the gastrostomy button has eliminated most of the catheter-related problems. Candidates for gastrostomy, particularly children with foregut dysmotility, must be carefully selected, undergo preoperative studies aimed at determining the degree of gastroesophageal reflux, and have appropriate long-term follow-up. Attention to technical detail is essential to avoid operative complications. A good working relationship between the surgeon, gastroenterologist, nurse, and patient's family is essential to minimize long term morbidity, particularly stoma-related problems. PMID- 1440158 TI - Evolving uses of laparoscopy in children. AB - As the technology evolves, the number of procedures that can be performed laparoscopically will continue to expand (Table 3). The impact on the field of pediatric surgery, which encompasses surgical oncology, gastrointestinal surgery, trauma, and gynecologic surgery, will be significant. There are several hurdles for the pediatric surgeon to overcome before beginning operative laparoscopy. The acquisition of the initial instrumentation is expensive, and the credentialing process may be time-consuming. And there remains a healthy suspicion on the part of many pediatric surgeons that these techniques represent a fad. We believe that operative laparoscopy has advantages and disadvantages. Some of the procedures require more time and are frequently tedious, thus trying the patience of the surgeon. It is difficult for experienced surgeons to subject themselves electively to the learning curve associated with a new procedure. While the benefits are mostly in the postoperative period, we believe exposure is vastly improved in obese patients. Patients appear to have less pain and postoperative ileus, and they may return to unrestricted activity sooner. We are still discovering which laparoscopic procedures can be done safely to the patient's advantage. Solving the dilemma of what procedures should be performed using laparoscopic techniques will require extensive experience and study, and minimally invasive surgery will be a subject of controversy and debate for many years. It is difficult to imagine that open cholecystectomy would once again become the standard. We predict that we will see a continued expansion in the types of procedures to be performed using minimal-access techniques. And in the future, we may have to justify our opening of a patient's abdomen when the procedure could have been performed laparoscopically, as is now the case for cholecystectomy in some areas of the country. PMID- 1440159 TI - Lasers in pediatric surgery. AB - The use of lasers in a variety of surgical disciplines has added new dimensions to operative techniques, allowing increased precision, improved hemostasis, and less tissue injury. Although lasers offer no significant benefit over some conventional pediatric surgical techniques, there are other procedures and disease conditions in which the use of laser technology provides major advances and improves outcome. The physics of laser technology and the unique characteristics and applications of the currently available lasers are discussed along with current and future applications in pediatric surgery. PMID- 1440160 TI - Uses of extracorporeal membrane oxygenation in nonneonatal respiratory patients. An update. AB - Neonatal extracorporeal membrane oxygenation (ECMO) has progressed rapidly from the experimental stage to a standard of care for certain infants who fail to respond to maximal conventional management. A broad diagnostic group of nonneonatal patients has now been supported by several different modes of ECMO with encouraging results. Selection criteria for nonneonatal patients that differ from those used for neonatal patients are emerging. Prospective randomized clinical trials are needed. PMID- 1440161 TI - Trends in pediatric trauma management. AB - Injuries are the leading cause of death in children 1 to 14 years old and result in permanent disabilities for thousands of children each year. Blunt trauma accounts for more than 60% of childhood injuries. Head trauma is most common, but the most severely injured children have multisystem injuries, frequently of the extremities, chest, and abdomen. The child's response to injury differs from that of the adult, and specific patterns are seen with blunt injury; recognition of these patterns is essential for proper management. The general surgeon coordinates the total care of the injured child, including the efforts of a variety of medical specialists, to provide cohesive and efficient care. PMID- 1440162 TI - Current surgical considerations in gastroesophageal reflux disease in infancy and childhood. AB - An understanding of gastroesophageal reflux disease in infants and children by the clinician requires a working knowledge of 18- to 24-hour esophageal pH monitoring and the motility disorders of the esophagus and stomach that may be associated with gastroesophageal reflux disease. The results of surgical therapy for childhood gastroesophageal reflux disease cannot be assessed accurately without this knowledge. Antireflux operations can be tailored to the child's situation, which includes a combination of clinical symptoms and findings on objective tests for reflux and associated alimentary-tract motility disorders. The presence of severe complications from gastroesophageal reflux disease in "asymptomatic" infants and children is a troublesome and not yet fully defined problem. Special areas include the documentation of gastroesophageal reflux disease as a cause of SIDS, the increased reporting of Barrett's esophagus and adenocarcinoma of the esophagus in childhood, and the effect of associated alimentary-tract motility disorders in children with CNS disease who have gastroesophageal reflux disease requiring surgical intervention. PMID- 1440163 TI - Current management of anorectal anomalies. AB - A significant amount of new information has been obtained concerning the early management of anorectal malformations. The surgical approach also has changed and improved the functional prognosis of children with these defects. Recommendations are made based on a series of 632 cases. A simplified approach to avoid the most common errors in the management of these defects is emphasized. Yet, there are still many children born with severe anatomic deficiencies who cannot expect normal bowel function; however, for this group, a bowel management program is available to help improve their quality of life. PMID- 1440164 TI - Review of head and neck lesions in infancy and childhood. AB - Common congenital and infectious lesions of the head and neck in infancy and childhood have been discussed. Those that are present at birth, asymptomatic, and frequently cystic are clearly benign lesions that require operative management for the potential complications of enlargement and infection. Solid lesions, particularly those of the lymph nodes, must be differentiated from neoplasms, particularly Hodgkin's disease and non-Hodgkin's lymphoma. Suppurative lymphadenitis is obvious from its local inflammatory signs, but the subacute and chronic adenopathies may be difficult to distinguish from neoplasia. An attitude that unless the benign nature of a lesion is clearly demonstrated, early excisional biopsy for histopathologic evaluation must be the rule will avoid delays in diagnosing those neoplastic lesions that can be treated successfully if managed early and aggressively. PMID- 1440165 TI - The changing role of amputation for soft tissue sarcoma of the extremity in adults. AB - The role of amputation in soft tissue sarcoma of the extremity has decreased at Memorial Sloan-Kettering Cancer Center during the last 20 years. In an attempt to determine the reasons for this change in therapy, an analysis of two separate databases involving 1,057 patients compiled during the periods of 1968 to 1978 and 1982 to 1990 was performed. The patients requiring amputation for soft tissue sarcoma of the extremity in the two databases (n = 233) were compared in an attempt to determine any significant differences between the two time periods. The groups were specifically compared for differences in risk factors, indications for amputations and the effect a decreasing incidence of amputation in the 1982 to 1990 group had on local recurrence and overall survival between the two groups. Despite similarity of risk factors and indications for amputation, the decreased incidence of amputation during the 1982 to 1990 period was associated with a significant decrease in local recurrence after amputation and no significant change in overall survival compared with the 1968 to 1978 group. Absence of local recurrence was associated with significant improvement in survival. Possible reasons for the shift in therapy, as well as the present and future role of amputation in soft tissue sarcoma of the extremity, are discussed. PMID- 1440166 TI - Appendiceal mucoceles and pseudomyxoma peritonei. AB - Mucoceles of the appendix and associated pseudomyxoma peritonei are a heterogeneous group comprising various histopathologic lesions with differing prognoses. Between 1983 and 1990, we treated eight patients with appendiceal mucocele, three cystadenomas and five cystadenocarcinomas, three of which had accompanying pseudomyxoma peritonei. All patients were more than 50 years of age. Women outnumbered men by seven to one. Preoperative diagnosis was acute appendicitis or appendiceal abscess in all instances of mucocele unaccompanied by pseudomyxoma peritonei. Ultrasound of the abdomen, together with paracentesis, diagnosed pseudomyxoma peritonei in two of three patients. Elevated carcinoembryonic antigen levels were found in six of the eight patients and monitoring of this parameter was useful in the early detection of the two recurrences observed. The three patients with cystadenomas remain free of disease after appendectomy. Of the five patients treated for cystadenocarcinoma by right colectomy, two underwent reoperation after recurrence of disease. One patient died 41 months later of intestinal obstruction caused by pseudomyxoma peritonei. Pseudomyxoma peritonei significantly decreases survival of patients with appendiceal mucocele. In these patients, aggressive initial surgical management, repeated if need be, is indicated. PMID- 1440167 TI - A prospective randomized trial of single versus multiple drains in the axilla after lymphadenectomy. AB - Increasing duration and amount of postoperative fluid formation after axillary lymphadenectomy delays final healing. We postulated that multiple drains (instead of a single drain) might decrease postoperative fluid accumulation by their greater proximity to points of leakage. We randomized 65 women with clinical stage I or II carcinoma of the breast to single or multiple drains. They were stratified for axillary dissection or modified radical mastectomy. For axillary dissection, randomization to multiple drains meant placement of four catheters in the axilla, and randomized to the single drain, one catheter in the axilla. For modified radical mastectomy, the patients randomized to multiple drains received four catheters in the axilla and one catheter under the inferior flap; the patients randomized to single drains had one catheter in the axilla and one catheter under the inferior flap. All catheters exited separately. The two arms (single versus multiple drains) were determined to be homogeneous in other variables that may affect postoperative fluid formation--age, size of the breast, weight, height, obesity, presence of previous surgical biopsy, excision of pectoralis minor muscle, excision of thoracodorsal complex, level of axillary dissection, number of lymph nodes, number and proportion of positive lymph nodes and whether or not the dominant hand was on the side operated upon. Single versus multiple drains had no clinically significant effect on the amount or duration of drainage, as an inpatient or outpatient, or total. We recommend a single drain to the axilla after lymphadenectomy. PMID- 1440168 TI - Comparison of intraoperative and endoscopic manometry of the sphincter of Oddi. AB - Despite the potential utility of intraoperative manometry of the sphincter of Oddi, limited data are available validating its use. The current study was undertaken to validate the method of intraoperative sphincter of Oddi manometry by comparing the pressure tracings obtained at operation (transduodenal sphincteroplasty and transampullary septoplasty) and endoscopy (preoperative) in the same group of patients. Seventy-four patients with idiopathic pancreatitis or unexplained disabling pancreaticobiliary pain had sphincter of Oddi manometry performed endoscopically and intraoperatively within six weeks of each other. Thirty-five patients had manometric evaluation of the bile duct segment of the sphincter of Oddi. The mean basal sphincter pressure determined endoscopically and intraoperatively was 41.1 +/- 6.4 millimeters of mercury (mean plus or minus standard error of the mean) and 42.0 +/- 6.8 millimeters of mercury (not significantly different, p > 0.05), respectively. There was no significant difference between the biliary sphincter phasic pressure, phasic frequency and phasic duration, as recorded by the two techniques. Fifty-five patients had manometric evaluation of the pancreatic duct sphincter. The mean basal sphincter pressure determined endoscopically and intraoperatively (after biliary sphincteroplasty) was 111.9 +/- 9.9 millimeters of mercury and 102.7 +/- 8.7 millimeters of mercury, respectively (not significantly different, p > 0.05). There was no significant difference in the pancreatic sphincter phasic duration and phasic frequency determined by the two techniques. However, the pancreatic sphincter phasic pressure was significantly higher when measured endoscopically (p < 0.001). Overall, 70 percent of patients benefited from surgical sphincter ablation therapy. Patients with an elevated basal sphincter pressure determined intraoperatively were more likely to improve than those with a normal basal sphincter pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440169 TI - Success with sacrospinous suspension of the prolapsed vaginal vault. AB - Sacrospinous ligament fixation of the prolapsed vaginal vault has proved very useful, but the complications of failure, hemorrhage, infection, nerve damage, incontinence and dyspareunia are reported. Experience with 51 operations performed by staff, and residents with supervision, has shown the value of certain preoperative and technical steps to avoid complications, including candidate selection; repair of enterocele; retropubic positioning of the bladder neck; repair of all pelvic support defects, and perineorrhaphy. Technical modifications are described. Results in these instances are tabulated: no recurrent prolapse; no transfusions; four narrow vaginas; two with stress incontinence; one pelvic cellulitis, and one ventricular fibrillation on the third postoperative day. We believe that most complications are preventable. PMID- 1440170 TI - Clinical use of synthetic absorbable cuff material for peripheral vascular anastomosis. AB - End to end arteriovenous (AV) fistulas were created using the cuff technique for hemodialysis in 12 patients with end stage renal disease. The cuff used was made of a synthetic biodegradable material, a lactic glycolic acid co-polymer with the same composition as absorbable surgical suture. Cephalic vein radial artery fistulas in the forearm were created electively in six patients to convert a Scribner shunt to a fistula in three patients and because of malfunction of a fistula created previously in three patients. Eleven patients underwent hemodialysis, with pump speeds of more than 200 milliliters per minute, and were evaluated for 129 to 477 days. These subcutaneous AV fistulas were maintained as patent functional veins and continued to function without complication. After five weeks, one patient had conversion to a prosthetic AV fistula because of poor venous maturation. The overall patency rate was 92 percent. The diameter of the AV anastomosis increased gradually with time. At 20 weeks, however, it reached more than 70 percent of the diameter of the radial artery lumen. These observations led us to believe that the cuff material used is biodegraded until 20 weeks and gives sufficient flexibility. In the future, the cuff method is expected to be clinically developed as another approach for vascular anastomosis. PMID- 1440171 TI - Treatment of peripancreatic fluid collections in patients with complicated acute pancreatitis. AB - We reviewed an experience with treatment of peripancreatic fluid collections in patients with complicated acute pancreatitis to identify clinical and computed tomography (CT) parameters that are helpful in the selection of patients for treatment and to assess treatment outcome. The extent of CT abnormalities determined a CT severity score (mild = 1, severe = 4). From 1985 to 1990, 650 patients were hospitalized with acute pancreatitis; a peripancreatic fluid collection was found in 36 patients (5.5 percent). Ten of 11 patients with successful outcome after no invasive treatment (group 1) had a low CT severity score of 1 or 2; mean serum albumin was 4.0 gram percent. Of 25 patients who had some form of drainage, 12 had a high CT severity score of 3 or 4 (p < 0.05) and a mean serum albumin of 3.4 grams percent (p < 0.05). Nine patients had only operative drainage (group 2) and 16 had CT-directed percutaneous catheter drainage (group 3). In group 3, percutaneous catheter drainage successfully drained the fluid collection in six patients, while ten patients needed an operation, in addition to percutaneous drainage, to effectively debride and drain the necrotizing pancreatic problem. As a result of the current review, we propose an algorithm for treatment of these patients. PMID- 1440172 TI - Axillary versus combined axillary and pectoral drainage after modified radical mastectomy. AB - Initial attempts to obliterate dead space and minimize fluid accumulation in patients after mastectomy using closed suction drainage, used insertion of a single axillary drain. Today, surgeons often insert two drains in the postoperative wound, one in the axilla and the other beneath the pectoral flaps. The current study was done to determine whether or not there is an advantage in using two drains rather than a single axillary drain after mastectomy. A randomized, clinical trial was conducted with 84 women undergoing modified radical mastectomy. Thirty-seven patients had one axillary drain and 47 had two drains placed postoperatively, one in the axilla and the other beneath the pectoral flaps. Follow-up results were obtained four weeks postoperatively for complication data, including seroma and hematoma formation, flap necrosis and infection. The average total drainage was 870.4 milliliters per patient in the group with one drain and 997.4 milliliters per patient in the group with two drains (p value not significant). The overall complication rate in the group with one drain was 35.0 percent compared with a rate of 31.9 percent for all complications observed in the group with two drains. These differences did not reach statistical significance. Comparing the frequency of each complication in the two groups again showed no significant difference. However, the data suggest a trend toward an increased incidence of flap necrosis in the group with two drains that used a drain beneath the pectoral flaps. Use of a single axillary drain after modified radical mastectomy seems to result in no increase in postoperative complications, is less costly and may assist in reducing the incidence of flap necrosis. PMID- 1440173 TI - Effects of pentagastrin and of the somatostatin analog (SMS 201-995) on growth of CT26 in vivo adenocarcinoma of the colon. AB - This study was done to investigate the effects of pentagastrin and of somatostatin analog (SMS 201-995) on growth of CT26 adenocarcinoma of the colon implanted in mice. Eighty Balb C mice were inoculated subcutaneously with 100,000 cells. Four groups of 20 mice each were treated with 0.1 milliliters of saline solution every eight hours; 250 micrograms per kilogram of pentagastrin every eight hours; 100 micrograms per kilogram of SMS 201-995 every 12 hours; 250 micrograms per kilogram of pentagastrin every eight hours, plus 100 micrograms per kilogram of SMS 201-995 every 12 hours. Tumoral weight, volume and deoxyribonucleic acid (DNA) content and mean survival rates were determined for each group. Control mice had tumors weighing 1,619 +/- 179 milligrams, of 1.47 +/ 0.2 milliliters to the third power and with 12.9 +/- 1.1 milligram of DNA, at 30 days after inoculation. The mean survival rate was 42.5 days. Pentagastrin administration increased the three parameters of tumoral growth by 40 percent and reduced survival time to 29.6 days (p < 0.01), while SMS 201-995 inhibited growth by 40 percent and prolonged survival time to 48.5 days (p < 0.01). Simultaneous administration of both peptides had no effects. These data suggest that pentagastrin has a trophic effect and SMS 201-995 an inhibitory effect on CT26 adenocarcinoma in mice. PMID- 1440174 TI - Systematic assessment of massive bleeding of the lower part of the gastrointestinal tract. AB - A study of 83 patients admitted with massive bleeding in the lower part of the gastrointestinal tract is presented using a diagnostic approach primarily of angiography and colonoscopy with the adjunctive investigations of scintigraphy, small intestine series and computed tomographic scan. The source of bleeding was identified preoperatively in 74 patients. Nine patients had a diagnostic laparotomy and the cause was found in an additional seven. A source was not identified in two patients at exploration and a blind resection was not performed. The two patients have not had recurrent bleeding four and nine years postlaparotomy. The sites of bleeding were colon in 44 patients, small intestine in 24 and the anorectum in 11. Sixty-five patients were treated operatively, two by angiographic embolization and two by endoscopic electrocoagulation. Fourteen patients were managed conservatively. The mortality rate was 10.8 percent and five patients rebled after treatment. We conclude that a thorough systematic assessment of patients with bleeding in the lower part of the gastrointestinal tract is important to localize the site of the hemorrhage. Exploratory laparotomy is the final diagnostic modality, and if a source has not been identified, a blind colonic resection should not be performed. PMID- 1440175 TI - Fibrin glue reduces seroma formation in the rat after mastectomy. AB - Fibrin glue is a biologic tissue adhesive that has been found to be useful in several areas of surgical treatment. Little has been written in the English literature, however, on its use in preventing postoperative fluid collections. We performed a prospective randomized trial to determine if fibrin glue could reduce postoperative fluid collections after mastectomy in a rat. Bilateral mastectomies and axillary lymph node dissections were performed upon 42 rats, one-half of which were treated with fibrin glue and one-half of which served as controls. The rats were sacrificed after seven days and inspected for quantity of fluid and adhesion formation. The mean plus or minus standard error of the mean fluid collections were 0.71 +/- 0.26 milliliter and 3.75 +/- 0.65 milliliter for the rats treated with fibrin glue and control rats, respectively. This was statistically significant (p < 0.0001). Seventeen of 21 rats treated with fibrin glue and four of 21 control rats were found to have fluid collections of less than 1 milliliter, again statistically significant (p = 0.00006). Furthermore, greater adhesion formation between the skin flap and chest wall was noted in the rats treated with fibrin glue. The results support the use of fibrin glue in clinical investigations to reduce postoperative fluid collections and also support the need to develop a standard reproducible method of producing fibrin glue or a commercial product free of transmissible disease. PMID- 1440176 TI - An analysis of prognostic factors in response to conservative treatment of postmastectomy lymphedema. AB - Postmastectomy lymphedema of the upper limb is usually managed conservatively. Patients are often advised to use elastic bandages or sleeves during the day: elastic compression is, in fact, generally considered the mainstay of lymphedema therapy by authors who advocate the addition of cyclical instrumental or physical treatments, such as pneumatic compression or manual lymphatic drainage. The results of elastic compression, however, have never been extensively analyzed. In the present study, we describe the patterns of response during six months of use of a standard elastic sleeve in a series of 120 patients with postmastectomy lymphedema. Univariate and multivariate analyses were performed to identify possible prognostic factors for a better or worse response. Overall, limb measurements were reduced by 14.7 percent, with weight gain after surgical treatment resulting as the only significant independent negative factor: patients who did not increase weight after mastectomy achieved nearly a 25 percent reduction of lymphedema. These results should be considered during the selection of patients for protocols of lymphedema treatment and the analysis of results. PMID- 1440177 TI - Transhiatal esophagectomy using a varicose vein stripper. PMID- 1440178 TI - A different technique of tying the surgeon's knot. PMID- 1440179 TI - Aseptic technique in microgravity. AB - Within the next decade, the United States will launch a space station into low Earth orbit as a preliminary step toward a manned mission to Mars. Provision of asepsis in the unique microgravity environment, essential in operative and invasive procedures, is addressed. An assessment of conventional terrestrial aseptic methods and possible modifications for a microgravity environment was done during the microgravity portion of parabolic flight on NASA KC-135 aircraft. During 110 parabolas on three flight days, a "surgical team" (surgeon, scrub nurse and circulating nurse) using a life size mannequin fastened to a prototype surgical "work station" (operating table), evaluated open and closed gloving (ten parabolas), skin preparation (six parabolas), surgical scrub methods (24 parabolas), gowning (22 parabolas) and draping (48 parabolas). Evaluated were povidone iodine solution, 1 percent povidone iodine detergent, Chloroxylenol with detergent, wet prep soap sponge, a water insoluble iodophor polymer (DuraPrep, 3M), disposable towels, disposable and reusable gowns, large and small disposable drapes with and without adhesive edges, disposable latex surgeon's gloves with and without packaging modifications and restraint mechanisms (tether, swiss seat, waist and foot restraint devices, fairfield and wire clamps and clips). Ease of use, provision of restraint for supplies and personnel and waste disposal were assessed. The literature was reviewed and its relevance to the space environment discussed, including risk factors, environmental contamination, immune status and microbiology. The microgravity environment, limited water supply and restricted operating area mandated that modifications of fabrication and packaging of supplies and technique be made to create and preserve asepsis. Material must meet stringent flammability and off-gassing standards. Either a chlorhexidine or povidone iodine detergent prepackaged brush and sponge would provide an adequate scrub plus preliminary cleansing of a dirty wound. Choice may depend on ease of removal from the water supply as well as sensitivity to each compound of individual crew members. Rinsing was achieved with sterile water soaked gauze. Drying would be more efficient with two small hand towels, which would be easier to manipulate in microgravity and require less stowage volume. Skin preparation highlighted unexpected packaging problems, as centrifugal force was required to "shake" the solution out of the container on to the mannequin. To minimize contamination, a gown should be folded in an accordion manner and fastened to the base of its sterile wrapper, so that an assistant can compensate for the lack of gravity by applying constant tension.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1440180 TI - Current clinical and pathologic perspectives on gastric stromal tumors. AB - Gastric stromal tumors are heterogeneous and poorly understood. Investigators have studied these tumors by histologic and immunocytochemical characteristics, but interlaboratory variations have impeded clinical application of these techniques. Although many gastric stromal tumors can be categorized as benign or malignant with some certainty, occasional instances may present great difficulty in this distinction. Uncertainty about malignant potential and the biologic factors of the lesion will therefore generally suggest excision with a 1 to 2 centimeter margin for diagnosis and definitive therapy of these tumors. Subsequent prognosis will be dictated primarily by tumor size, histologic factors and mitotic index. Gastric stromal tumors in young women should suggest the possibility of Carney's triad. Functional extra-adrenal paragangliomas and pulmonary chondromas should be sought preoperatively. The paraganglioma should be managed first and the gastric lesion then addressed. Distal gastrectomy of at least 50 percent would seem to represent a reasonable resection limit. Identification of the specific cellular biologic factors of these lesions will be necessary to accurately classify particular tumors, gauge prognosis and individualize their management. PMID- 1440181 TI - In defense of the anatomic blackboard drawing. PMID- 1440182 TI - Anatomical bases of the pediculated pisiform transplant and the intercarpal fusion by Graner in Kienbock's disease. AB - Anatomic characteristics of the lunate, the pisiform and the capitate were compared in order to support the use of a pisiform transplant or the intercarpal fusion by Graner in advanced stages of Kienbock's disease. Fifty lunate and pisiform bone pairs and 20 wrist specimens served for morphological and functional investigations. In view of the present results, the pisiform, after a rotation of 90 degrees, should be implanted in the lunate box with its longitudinal diameter oriented to the dorsopalmar plane. Despite the small pisiform volume, maintainance of carpal height is assured by its relatively large dorsopalmar diameter. The rotated position permits use of existing soft tissue structures and improves the conditions of force transmission. Measurements comparing the radii of curvature of the original lunate and the substitute pisiform surfaces show a good correspondence proximally and a reduction of the articular congruity distally, due to the flatness of the pisiform surface. The palmar convexity of the pisiform adapts better to the distal radius facet than the capitate head, which replaces the lunate in Graner's surgical procedure. PMID- 1440183 TI - Anatomical basis of the anterior cervical spine approach: topographic study of the nerve structure. AB - The results of the surgical anterior approach to the cervical spine are marked in a number of cases by dysphagia and dysphonia, especially when the approach is extensive or performed at the upper cervical spine. 35 cadaver dissections were performed to define the topography of the nerve structures during operative exposure at various vertebral levels: superior and recurrent laryngeal nerves, hypoglossal nerve and its superior root of the ansa cervicalis. The authors suggest some technical improvements, for each stage of surgical dissection. PMID- 1440184 TI - Anatomical bases of percutaneous surgery for calculi in horseshoe kidney. AB - Horseshoe kidney is a renal fusion which combines three anatomic abnormalities: ectopia, malrotation and vascular changes. These anomalies can be recognised separately to varying degrees in unfused kidneys. Necessary modifications of the standard technique for percutaneous nephrolithotomy (PNL) are directly deducible from analysis of the anatomic data of the imaging of horseshoe kidneys. We report our experience with 5 patients (7 kidneys) who underwent PNL for calculi in horseshoe kidneys. The percutaneous approach was performed under ultrasound and fluoroscopic monitoring. In situ disintegration by ultrasonic lithotripsy and nephrostomy drainage were necessary in all cases. Modifications of the standard PNL procedure are related to the anatomic changes. The lower abdominal position of a horseshoe kidney necessitates upper or middle calyceal puncture, while the malrotation necessitates a more posterior puncture. Monitoring of the puncture needle by fluoroscopy as it is advanced postero-anteriorly is more difficult and the risk of the surgeon's hand entering the radiation path is increased. The renal pelvis is deep and a long endoscope may be required. Aberrant segmental vessels may create potential hazards. The majority of problems in location can be avoided by use of an ultrasonically guided needle. Percutaneous nephrolithotomy is the treatment of choice for calculi in horseshoe kidneys for the following reasons: the high incidence of recurrent lithiasis in horseshoe kidney and the complexity of repeated surgical approaches diminish the acceptable results of open surgery; difficulties in focussing on the calculi and drainage problems militate against the success of extracorporeal shock wave lithotripsy (ESWL); PNL has a good success rate and the least morbidity. PMID- 1440185 TI - Arterial supply of the acetabulum in the fetus: application to periacetabular surgery in childhood. AB - The need to perform triple osteotomies of the pelvis passing very close to the articular surface leads to the isolation of bony fragments whose vascularisation may be precarious. To assess the risks of such surgery, we undertook an anatomic study of the vascularisation of the acetabulum in the fetus. 53 specimens were injected to study the vessels to the acetabulum and their distribution within the osteocartilaginous specimen. The acetabular a., a branch of the obturator a., gives a central pedicle distributed to the acetabular fossa, the triradiate cartilage and ending in the three primary bony components. The superior gluteal, inferior gluteal, internal pudendal and obturator aa. form a periacetabular vascular circle. The abundant vascularity of the acetabulum makes massive necrosis improbable in the child. However, there is a zone of precarious anastomosis at the anterior portion of the acetabulum. PMID- 1440186 TI - Fetal development of the pyloric muscle. AB - The fetal development of the pyloric muscle was studied in five human embryos (crown-rump length 5 to 31 mm) and in ten fetuses aged 3 to 9 months. Samples of pyloric muscle were obtained during operation for pyloric stenosis in two infants aged six weeks. Anatomo-radiologic, morphologic and immunohistochemical studies were made on this material, from which it emerged that the pylorus is identifiable by means of specific markers from the 40th day. Its two-layered muscular structure is described in detail. The mechanism of sphincteric function is reviewed. This study assumes clinical importance in the context of the etiopathogenesis of hypertrophic stenosis of the pylorus. PMID- 1440187 TI - Induced and genetic mouse middle ear ossicular malformations: a model for human malformative ossicular diseases and a tool for clarifying their normal ontogenesis. AB - Oral administration of 13-cis retinoic acid (RA) to pregnant mice on the 9th gestation day provokes important malformations of the middle ear ossicles, associated with a general kind of craniofacial dysmorphogenesis evoking the human mandibulofacial dysostosis. The malleus, incus and stapes are affected. The malleus exhibits a handle separated from its head and keeping a persistant relationship with the tubotympanic recess. The stapes makes no contact with the otic capsule. The malformation pattern is visible early as shown by the appearance of an abnormally curved Meckel's cartilage at day 12, followed by the development of atypically shaped ossicular anlagen. The mouse "far" (first arch malformation) mutation is responsible for minor ossicular abnormalities which disrupts the normal relationships between the stapes, Reichert's cartilage and stapedial muscle. The administration of RA to pregnant mice and the comparison with a genetically induced malformation (the mutation far) provides some interesting information about the postulated mechanisms of human middle ear dysmorphogenesis, as well as precious data about the features of normal ossicular primordia formation. The comparison of these features with human middle ear abnormalities as revealed by medical imaging sheds light on human malformation patterns and provides a better understanding of normal and abnormal radiologic ossicular aspects. PMID- 1440188 TI - Relationship between the development of diaphragma sellae and the morphology of the sella turcica and its content. AB - The impaired formation of the diaphragma sellae may lead to the development of the empty-sella syndrome. This structure, when fully formed, is a protective barrier against the pulsating action that the cerebrospinal fluid exerts on the sellar content. There are anatomical features which support this belief, but they also suggest that the development of the diaphragma sellae is a factor which determines the morphology of the sella turcica and its contents. Those human specimens which do not have diaphragma sellae or in which it is only partially developed, are characterized by a smaller hypophysis, always located at the inferior and/or posterior half of the sella, with a larger sellar volume and frequently greater fragility of its bony walls. These findings, although rare (5% of the cases), are indirect signs of the important role which the diaphragma sellae plays in the sellar region. PMID- 1440189 TI - Three-dimensional reconstruction of the hip muscles on the basis of magnetic resonance images. AB - MRI in combination with three-dimensional reconstruction is pre-eminently suitable for the study of the human musculoskeletal system in vivo in an accurate and detailed way. MRI provides the possibility of studying superficial as well as deep muscles under tension in the living state. Bones, muscles, tendons and adipose tissue are clearly visible. Parts can also be distinguished within a muscle. After reconstruction of the 2-D images the geometry of the muscles and muscle parts can be visualized from different angles. This leads to a deeper understanding of the biomechanics and functional anatomy of the musculoskeletal system of the human body. In this paper the morphology of the muscles around the hip was studied in three subjects in vivo on the basis of three-dimensional (3-D) reconstructions of two-dimensional (2-D) MR images. PMID- 1440190 TI - Analysis of length and surface area of each segment of the large intestine according to age, sex and physique. AB - Length, diameter and surface area of each of 6 segments of the large intestine were determined and calculated in 920 Japanese patients who underwent barium enema. Of the length and surface area measurements obtained, those of the transverse colon were the largest, followed by those of the sigmoid colon. The diameter of the ascending colon was the largest, while those of the descending colon and sigmoid colon were the smallest. There were various sex differences in size of the large intestine. Length and surface area of the entire large intestine in males were shorter and smaller respectively than those in females. Lengths of the cecum, ascending colon, transverse colon and rectum in males were shorter than those in females. Diameters of the descending colon, sigmoid colon and rectum in males were larger than those in females. Total surface areas of the ascending colon and transverse colon in males were smaller than those in females, while total surface areas of the descending colon, sigmoid colon and rectum in males were larger than those in females. Length of the entire large intestine tended to be increased with age. Length and surface area of the entire large intestine tended to be increased with an increase in physical dimensions in females. PMID- 1440191 TI - Trans-uterine venography. Normal anatomy and pathologic appearances. AB - From a series of 110 trans-uterine venographies, the authors present the normal radiological anatomy of the uterine venous vascularization and of its efferent venous drainage. They also present the most frequent variations from normal and examples of the pathologies encountered. PMID- 1440192 TI - Biometry of the infrarenal inferior vena cava measured by computed tomography. Clinical applications. AB - In a previous study based upon the cavography of 100 patients, we determined that the average diameter of the infrarenal inferior v. cava (IIVC) was 21.3 mm (range 10-31 mm) at its end [1]. We discuss the value of different methods to measure IIVC, and particularly computed tomography (CT) scans reviewed in our department. It showed that the largest diameter of IIVC was not in a frontal plane and the width observed in a cavography was in fact the projection of a transverse diameter on the film. The real diameter of the IIVC is larger than that showed by cavography. This present study shows the results of measurements of the IIVC obtained from 50 consecutive CT scans. The average transverse diameter is 24.26 mm (range 14-33.3). The average anteroposterior diameter is 13.4 mm (range 5-22) and the average angle alpha between the transverse diameter and the frontal plane is 30 degrees 45' (range 12 degrees-55 degrees). We discuss the different methods of measurement of IIVC and we conclude that at present, CT scan is one of the most reliable methods to measure the real diameter of IIVC. PMID- 1440193 TI - Morphologic aspects of biceps brachii in the rat: application to brachial plexus reconstruction (27.3.92). PMID- 1440194 TI - Role of the first dorsal metacarpal artery in the construction of pedicled bone grafts (27.3.92). PMID- 1440195 TI - Role of class I molecules of the major histocompatibility complex in cytotoxic T cell function in health and disease. PMID- 1440196 TI - Mechanisms of transplantation immunity. AB - In summary, this chapter describes the biology and genetics of the major and minor histocompatibility antigens and the nature of in vitro and in vivo immune responses to them and to tissue-specific antigens. It reviews the nature and action of immune response genes. It gives an account of how tolerance to histocompatibility antigens was originally defined and the prospects of intervention aimed at establishing tolerance to these and tissue-specific antigens in adult animals, including man. PMID- 1440197 TI - Genetic analysis of susceptibility to type 1 diabetes. PMID- 1440198 TI - The immunogenetics of rheumatoid arthritis. PMID- 1440201 TI - Clinical procedures review: another casualty of a litigious society. PMID- 1440200 TI - A role for major histocompatibility complex-binding peptides in the immunotherapy of autoimmune disease. PMID- 1440199 TI - Multiple sclerosis and its animal models: the role of the major histocompatibility complex and the T cell receptor repertoire. PMID- 1440202 TI - Transcranial Doppler sonography in carotid-cavernous fistulas: analysis of five cases. AB - Transcranial doppler sonography was performed transorbitally in five patients clinically diagnosed as unilateral carotid-cavernous fistula. Dural arteriovenous malformation related-shunts were detected in all the patients. In the normal eyes, the only doppler signals observed at an insonation depth of 45 to 55 mm were those of the ophthalmic artery. In the affected eyes, abnormal doppler signals with relatively higher flow velocity and lower resistance were observed. In three of the cases, these abnormal signals showed a flow directed anteriorly or away from the cavernous sinus, consistent with changes in the ophthalmic veins caused by the presence of the shunts. In two cases, however, the observed flows were directed posteriorly, the normal direction of these veins. The possible explanations for this discrepancy are discussed in relation with angiographic findings. The use of transcranial doppler might provide a better understanding about hemodynamic changes in carotid cavernous fistulas. PMID- 1440203 TI - Mesial temporal subdural electrode as a substitute for depth electrode. AB - As a substitute for depth electrodes, mesial temporal subdural electrodes were devised. This electrode has a slender trapezoid shape and is easily introduced to the inner uppermost portion of the parahippocampal gyrus. Our results have shown that mesial temporal electrodes can detect not only interictal spikes but also subclinical and clinical seizure discharges from the mesiolimbic structures, and they have excellent capability for lateralization of the mesial temporal epileptic focus. If mesial temporal subdural strips are used in combination with lateral temporal subdural grids, comprehensive understanding of the focus distribution throughout the temporal lobes will be possible without using depth electrodes. PMID- 1440204 TI - Multimodality treatment of deep periventricular cerebral arteriovenous malformations. AB - The surgical treatment of arteriovenous malformations (AVMs) located in deep periventricular regions such as the basal ganglia is associated with marked morbidity and mortality. Approaches through critical brain regions afford limited exposure of the lesions, while surgical dissection is sometimes complicated by acute severe brain swelling and/or hemorrhage in the surrounding tissues. In our approach to deep AVMs, our regimen has evolved from direct staged microsurgical excision under routine fentanyl-N2O-relaxant anesthesia (first four patients) to the use of elective high-dose barbiturate anesthesia (subsequent 12 patients). In the first group of four patients, 11 operations were performed. Two patients improved, one of whom returned to normal neurologically. There were three episodes of acute brain swelling and/or hemorrhage. One patient died as a result, and another deteriorated. In the second group of 12 patients, all but two lesions were completely excised. Among the 10 patients in whom the AVM was completely excised, seven improved, six of whom achieved a good to excellent outcome, with two regaining full neurologic function. Three patients worsened (one as the result of acute brain swelling and/or hemorrhage). There was no death in this group. Only one incidence of acute brain swelling and/or hemorrhage occurred in 26 operations. Even though the number of patients is too small in the first group for meaningful statistical comparison, our intraoperative observations and postoperative results suggest that our evolved multimodality regimen, such as staged excision and the use of elective high-dose barbiturates, was likely to have contributed to the improved treatment results of these formidable lesions. PMID- 1440205 TI - Hemifacial spasm due to tumor, aneurysm, or arteriovenous malformation. AB - The authors report eight cases of so-called symptomatic hemifacial spasm. They had gross pathological lesions such as a tumor (one epidermoid, one neurinoma, and two meningiomas), vascular malformation (one medullary venous malformation and two arteriovenous malformations), and aneurysm. In all four cases with a tumor, no artery compressed the facial nerve at the root exit zone. In three of the four cases, the hemifacial spasm disappeared after removal of the tumor in contact with the facial nerve. Compression or encasement of the facial nerve by the tumor was the pathogenesis of the hemifacial spasm in these three cases. The remaining case with tumor (tentorial meningioma) did not have a mass or vessel that directly compressed the facial nerve at the root exit zone. However, the hemifacial spasm disappeared after the removal of the tumor. In a case with a medullary venous malformation with arterial component, an engorged draining vein compressed the root exit zone of the facial nerve. In the remaining three vascular cases--two cases of arteriovenous malformation and a case of saccular aneurysm--enlarged feeding arteries and an aneurysm directly compressed the root exit zone of the facial nerve. Not only arterial or venous but also mass compression can cause hemifacial spasm in some symptomatic cases. Surgical decompression of the facial nerve from the causative organic lesion is the primary choice of treatment. PMID- 1440206 TI - Vertebral hemangioma causing spinal cord compression during pregnancy. AB - Hemangiomas of bone are extremely common vascular tumors that are most commonly discovered as incidental findings in the vertebral column. Infrequently, these benign lesions may cause local or radicular pain and neurologic deficits, from myeloradiculopathy to paralysis. This report describes the occurrence of a symptomatic vertebral hemangioma during pregnancy, in order to illustrate current methods for diagnosis and treatment of these lesions when associated with spinal cord compression. The possible mechanisms by which they may become symptomatic during pregnancy are reviewed. PMID- 1440207 TI - Neurinoma of the third, fourth, and sixth cranial nerves: a survey and report of a new fourth nerve case. AB - A rare case of trochlear nerve neurinoma is described. Including this case, the number of reported intracranial tumors arising from the sheaths of the third, fourth, and sixth cranial nerves is 38. By site and relationship to the nerve segment, they fall into three groups: cisternal, cisternocavernous, and cavernous. In cisternal tumors of the third and sixth nerves, paresis of the nerve hosting the tumor is the unique nerve deficit; by contrast, in those of the fourth nerve, paresis of the trochlear nerve can be absent and that of the third nerve present. In the latter tumors, a peculiar ataxic hemiparesis syndrome is produced by midbrain compression. Cisternocavernous neurinomas often cause symptoms of intracranial hypertension, while cavernous neurinomas bring about two clinical features: paresis of one or more nerves of the cavernous sinus and a clinicoradiological orbital apex syndrome. At surgery, generally cisternal neurinomas are totally removed and the nerve source of the tumor identified; in cisternocavernous and cavernous neurinomas, total removal of tumor and identification of the parent nerve have been reported in only half of the cases. In the majority of parasellar neurinomas, clinical differences can be found between those arising from the nerves governing eye movement and those arising from the gasserian ganglion. PMID- 1440208 TI - Repositioning of the tortuous vertebrobasilar artery for trigeminal neuralgia: a technical note. AB - A patient with trigeminal neuralgia caused by a tortuous vertebrobasilar artery is reported. To obtain safe and certain neurovascular decompression of the trigeminal nerve, the tortuous vertebrobasilar artery was repositioned by pulling it toward the dura mater of the clivus using a synthetic vascular slip. The authors describe the technique of repositioning of the tortuous vertebrobasilar artery and its usefulness. PMID- 1440209 TI - Implications for the pathogenesis of aneurysm formation: metastatic choriocarcinoma with spontaneous splenic rupture. Case report and a review. AB - We report a case of ruptured intracranial aneurysm from metastatic choriocarcinoma in a patient presenting with intracerebral hemorrhage. Operative evacuation of the hematoma with clipping of a distal right middle cerebral artery aneurysm was performed. Postoperatively, the patient developed hypovolemic shock from spontaneous splenic rupture. Histopathologic examination of the cerebral aneurysm showed choriocarcinoma invading the vessel wall. Metastatic choriocarcinoma should be considered in the differential diagnosis of intracerebral or subarachnoid hemorrhage in women of child-bearing age. PMID- 1440210 TI - Primary carcinoma of the choroid plexus in the lateral ventricle. PMID- 1440211 TI - Cavernous angioma of the posterior fossa dura mimicking a meningioma: case report and review of literature. AB - A cavernous angioma of the posterior fossa dura was discovered incidentally on neuroimaging studies. The clinical and pathologic features of this lesion are described. Although it has been reported to arise in the posterior fossa and the tentorium cerebelli, we present the first case of such a malformation arising from the dura of the posterior fossa. PMID- 1440212 TI - Benign meningioma with a short latency period following irradiation. AB - Meningiomas have been reported following radiation of the head, usually with a long latent interval between exposure and the diagnosis of the new tumor. We report a benign meningioma resected approximately 3 1/2 years after radiation therapy for a glioma, which represents an unusually short latent interval between radiation and new tumor growth. PMID- 1440213 TI - The association of cervical spondylosis and multiple sclerosis. AB - The diagnostic and therapeutic considerations produced by the coexistence of cervical spondylosis and multiple sclerosis are complex. We have encountered six patients, affected by both multiple sclerosis and cervical spondylosis, in whom neurosurgical procedures were performed. The diagnosis of multiple sclerosis was confirmed by a combination of clinical, neuroimmunologic, electrophysiologic, and neuroradiologic findings. The diagnosis of spondylosis with spinal cord compromise was confirmed by myelography and computed tomographic scan in all cases, and by magnetic resonance imaging in four. Surgery was followed by lasting clinical improvement in two patients, transient improvement in one, and no change in the other three. Our experience confirms that multiple sclerosis and cervical spondylosis can coexist and suggests that this coexistence may result in an interaction that compounds the deleterious effect on the nervous system. Diagnostic evaluations of patients, particularly young patients, with symptoms of cervical spondylosis should include consideration of the possible coexistence of multiple sclerosis. The evaluation of a patient with known multiple sclerosis who develops new signs of cervical spinal cord dysfunction should always include spinal neuroimaging studies. When progression of symptoms coincides with documented progression of anatomic compression, surgical intervention can yield good results. PMID- 1440214 TI - Use of propofol (Diprivan) for awake craniotomies: technical note. AB - We describe the use of propofol (Diprivan) to provide patient comfort during the initial stages of awake craniotomies. PMID- 1440215 TI - Meningioma in a neonate: case report. AB - A 10-day-old female with a parasagittal meningioma presenting as a subcutaneous tumor is reported. Meningiomas within the 1st month of life are rare. The clinical and pathological characteristics of congenital meningioma are reviewed. PMID- 1440216 TI - Cerebral berry aneurysms in identical twins: a case report. AB - A pair of identical twins in whom cerebral berry aneurysms were found is reported. One presented with epilepsy, and the aneurysm was discovered incidentally. The other presented with a spontaneous bleed, which was fatal. PMID- 1440217 TI - Intracerebral injury following thermocoagulation of the trigeminal ganglion. AB - An unusual postoperative complication of percutaneous thermocoagulation of the gasserian ganglion is reported. Computed tomography and magnetic resonance imaging of the brain disclosed an intracerebral lesion following the surgical procedure. Some rare abnormalities of the skull base could increase the risk of such complications. A meticulous surgical technique with fluoroscopic and neurophysiological control is mandatory in any percutaneous procedure on the trigeminal ganglion. PMID- 1440218 TI - Growth of a giant aneurysm following complete thrombosis by detachable balloon occlusion. AB - A giant basilar artery aneurysm demonstrating growth and causing neurological deterioration even after complete detachable balloon occlusion is reported. Autopsy revealed total thrombosis of the aneurysm and a hemiconcentric, onion skin-like, laminated structure. Numerous vascular channels and multiple fresh intramural hemorrhages were noted within the outer margin of the aneurysmal wall. Repeated intramural hemorrhages appeared to have been responsible for the aneurysmal laminated structure and contributed to progressive aneurysmal growth. This case demonstrates that the growth of some giant aneurysms is not dependent upon the continuity with the parent artery, and progressive enlargement cannot always be prevented by balloon occlusion. PMID- 1440219 TI - Acute intramedullary spinal cord abscess: case report. AB - We report the first case of an acute pyogenic intramedullary cervical spinal cord abscess, brain abscesses and meningitis due to an unusual anerobe, Bacteroides disiens. The importance of spinal magnetic resonance imaging for establishing the diagnosis is emphasized. PMID- 1440220 TI - A case of double-compartment hydrocephalus presenting with opisthotonus. AB - Double-compartment hydrocephalus, a rare shunt complication, is caused by occlusion of the aqueduct and the fourth ventricular outlets after shunting of the lateral ventricles. Dilation of the fourth ventricle causes brain-stem dysfunction and cerebellar signs. A case of double-compartment hydrocephalus presenting with opisthotonus is presented, and the relevant literature is reviewed. PMID- 1440221 TI - Intraventricular craniopharyngioma: report of two cases and review of the literature. AB - Two unusual cases of purely intraventricular craniopharyngioma are presented. Both patients complained of headache as a sign of increasing intracranial pressure, but neither other neurological deficits nor hormonal disorders were present. Magnetic resonance images showed a mass lesion located within the third ventricle. Surgery confirmed that these two tumors were completely confined within the third ventricle, and histologically they proved to be squamous papillary craniopharyngiomas. Review of the literature demonstrates that craniopharyngiomas at this location have many common features and would appear to form a distinct entity. PMID- 1440222 TI - Serial development of 'de novo' aneurysms after carotid ligation: case report. AB - A case demonstrating the serial development of "de novo" aneurysms following common carotid ligation is presented. Persistence of the hemodynamic changes caused by carotid ligation, proven by ophthalmodynamometry performed twenty-five years later, might be the underlying basis for the serial formation of de novo aneurysms. The need for a program of routine neuroradiological follow-up in patients undergoing carotid ligation is discussed. PMID- 1440223 TI - Multiple spinal neurinomas presenting visual disturbance as the initial symptom: case report. AB - A case of multiple spinal neurinomas with visual disturbance is reported. A 63 year-old man was admitted with a complaint of progressive visual disturbance due to papilledema without spinal symptoms and signs. The neuroimaging studies demonstrated communicating hydrocephalus and two mass lesions in the cauda equina. Both tumors were found to be neurinomas. Intracranial hypertension secondary to spinal tumors is unusual, and multiple spinal neurinomas are rare. In the patient without spinal symptoms and signs, it is difficult to make a diagnosis of spinal tumor. Importance of checking for a spinal cord lesion by magnetic resonance imaging in such a case is stressed. PMID- 1440224 TI - Lumbar disk lesions in retrospect and prospect. PMID- 1440225 TI - The knife that saves. Memoirs of a Lahey Clinic surgeon. PMID- 1440226 TI - Cerebrospinal fluid rhinorrhea occurring in long-term bromocriptine treatment for macroprolactinomas. PMID- 1440227 TI - In vitro fertilization and frozen bone flaps. PMID- 1440228 TI - Endometrial carcinoma in patients aged 75 years or older: outcome and complications after postoperative radiotherapy or radiotherapy alone. AB - A retrospective analysis is reported of 89 patients at least 75 years old (median age 79 years) treated with irradiation for endometrial carcinoma between 1972 and 1989, the median follow-up being 39 months. In 66 patients radiotherapy was given postoperatively and in one case preoperatively, 22 patients were treated with radiotherapy alone: intravaginal insertions exclusively in 22 patients (median dose 60 Gy to the mucosa) and combined with external radiotherapy in 53 patients (median external target dose 45 Gy; three or four fields, all treated daily, 1.8 to 2.0 Gy per fraction, five fractions per week; 30 Gy to the vaginal mucosa with low-dose rate). A few patients were treated with external radiotherapy or intrauterine insertions only. 65% of the patients treated with radiotherapy alone and 34% of the patients receiving postoperative radiotherapy had FIGO stage II or III disease. Five-year actuarial overall survival and disease-free survival for all patients with adenocarcinomas treated with curative intent was 47.5% and 57.2%, respectively. In 48 patients with surgical stages I and II, treated with postoperative adjuvant radiotherapy, overall actuarial survival is 58.2% and disease-free survived 65.5% at five years. After postoperative vaginal insertions only, no vaginal recurrence occurred. With combined external and intravaginal radiotherapy in surgical stage I and II, 4/36 patients (11%) showed a recurrence in the vagina only, the abdominal and pelvic recurrence rate being 8.3%. Grade 3 to 4 late toxicity was observed in 6/53 patients (11.3%) treated with external and intravaginal radiotherapy. However, in patients receiving external radiotherapy less than 45 Gy and intravaginal radiotherapy 30 to 40 Gy, as is standard postoperative adjuvant treatment today, only one grade 3 late toxicity was observed in 17 patients (5.9%). We conclude, that treatment of elderly patients with adenocarcinoma of the uterus should follow the same pattern as in younger patients, the acute side-effects and late toxicity of radiotherapy being similar. PMID- 1440229 TI - Clinical assessment of tumor clearance during radiotherapy as a prognostic factor of early glottic carcinoma. AB - From 1967 through 1985, 358 cases of early glottic carcinoma were treated with telecobalt therapy at the Department of Radiology, Osaka University Medical School. Among 278 cases treated with 2 Gy a day, the tumor response of 262 cases at 40, 50 and 60 Gy were evaluated by direct or indirect laryngoscope. The five year local control rates of these evaluable cases of T1 and T2 glottic carcinoma were 79% and 70%, respectively. The local control rates of T1 glottic carcinoma with tumor clearance and persistence at 40 Gy were 83% (119/143) and 64% (43/67), and those of T2 cases were 86% (18/21) and 58% (18/31), respectively. The local control rates of the cases with tumor clearance and persistence at 40 Gy were same between T1 and T2 cases. The tumor clearance rates of T1 cases were significantly higher than those of T2 cases (p < 0.005). T2 glottic carcinoma had larger tumor volumes and slower tumor regression and resulted in lower control rates compared with T1 glottic carcinoma. The difference in the radiation dose of T1 and T2 glottic carcinoma with the same clearance rate was estimated as 15 Gy using logit analysis. PMID- 1440230 TI - Ideal dose level in treatment planning optimization. AB - The biological response of the tumor is expressed in terms of tumor control probability (TCP) and its dependence on the inhomogeneous dose distribution throughout the tumor volume is studied. The ideal dose level to which the prescribed dose must be referred is derived, by employing a formula based on the linear quadratic model. To administer the prescribed dose to the ideal dose level renders the tumor control probability equal to that one corresponding to a uniform irradiation of the tumor. For the normal tissue irradiated a normal tissue complication probability index (NTCPI) is also defined and calculated. The comparison between NTCPIs of competing plans supports the optimization. In general the resulting ideal dose level is lower than the mean dose level, but not necessarily equal to the minimum in the tumor. This result shows the possibility of administering the prescribed dose to a dose level higher than the minimum, maintaining the tumor control probability at a good level and consequently lowering the complications to the normal tissue. The method offers a general support for the choice of the reference dose level and of the better technique. An example of application of the method is shown. PMID- 1440231 TI - The cytoskeleton and proliferation of melanoma cells under hyperthermal conditions. A correlative double immunolabelling study. AB - Hyperthermia provides a potent therapeutical tool of cancer treatment, the cell biological effects of which are fairly understood. In the present study we applied hyperthermal shocks of 42 degrees C and 44 degrees C to human melanoma cells under tissue culture conditions. The integrity of the microtubular (mT) system and rate of DNA replication was assessed by indirect immunofluorescence using antibodies to tubulin as an mT marker and to BrdU as an indicator for DNA replication. Through this approach we obtained evidence that heat (44 degrees C for 60 min) exerts a profound damaging effect on the mT system accompanied by a change in the phenotypical appearance of melanoma cells. DNA replication, however, was still in progress in a significant number of heavily afflicted cells. From these data we conclude that a therapeutic regiment combining hyperthermia and mT inhibitors might prove useful in the treatment of human melanomas. PMID- 1440232 TI - Micronucleus assay prediction and application optimized by cytochalasin B-induced binucleated tumor cells. AB - Improvement in the predictive assertion of the micronucleus assay was achieved by treating human malignant melanoma cells (Mewo) with cytochalasin B (CB), generating binucleated cells (BNC) representing cells after a single karyokinesis. Optimal cell binucleation was determined by testing several cytochalasin B concentrations and different incubation times. On average, 56% binucleated cells were found after incubation with 2 to 3 micrograms/ml cytochalasin B for 48 h. Cells with at least one micronucleus (Mn) were defined as fraction of cells with micronuclei and describes the degree of damaged cells. We found in binucleated cells 2.2 fold the fraction of cells with micronuclei than in mononucleated cells (MNC), as expected assuming that an induced micronucleus is associated with only one single daughter cell after mitosis. The mean of micronuclei per binucleated cells, however, was enhanced about 2.9 fold in relation to that of micronuclei per mononucleated cells and is related to the nuclear damage per cell. The application of cytochalasin B did not enhance the fraction of damaged cells although the degree of the injury per cell is intensified. A micronuclei promoting or inhibiting effect of the experimental design due to changes in cell proliferation was excluded by cytofluorometric investigations of DNA content and synthesis after cytochalasin B application. A comparison of the modified with the conventional micronucleus assay shows the superiority of the former. PMID- 1440233 TI - Protection of mouse oesophageal mucosa against gamma rays injury. AB - The alterations in the oesophageal epithelium were studied in mice after a single whole-body exposure to 7.5 Gy of Co-60 gamma rays in presence or absence of 2 mercaptopropionyl glycine. The epithelium showed an increase in the thickness which reached a maximum on the third day and then decreased gradually up to seventh day after irradiation in the non-drug treated group. In the 2 mercaptopropionyl glycine treated animals the epithelial thickness remained in the normal range except on the day 7 when it was significantly lower than normal. The total cell population registered a steady decline from one to seven days post irradiation in both groups, but the number of cells was more in the 2 mercaptopropionyl glycine treated group. The number of pycnotic nuclei showed an inverse relationship to the total cell population, it increased continuously up to seven days in both the protected and non-protected groups. However, pycnotic nuclei were significantly lower in the protected group on days 3, 5 and 7 in non protected group. PMID- 1440234 TI - Adjuvant therapy for patients with colon and rectal cancer: clinical indications for multimodality therapy in high-risk groups and specific surgical questions for future multimodality trials. PMID- 1440235 TI - Retroperitoneal Castleman's disease. AB - A case of Castleman's disease localized in the retroperitoneal space is reported. A 29-year-old patient had a mass 15 cm in diameter with radial calcification. After surgical resection, both the patient's anemia and hypergammaglobulinemia disappeared. Castleman's disease should be considered when facing a solid retroperitoneal or mesenteric mass, mainly if anemia and hypergammaglobulinemia are present. Previous reports about this unusual condition are reviewed. PMID- 1440236 TI - Laparoscopic cholecystectomy during pregnancy in symptomatic patients. AB - BACKGROUND: The management of symptomatic biliary tract disease during pregnancy is controversial. Although most patients receive temporizing medical therapy, some authors have advocated a more aggressive surgical approach. We have extended this surgical approach to include laparoscopic cholecystectomy. METHODS: Five women with pregnancies at 13 to 23 weeks' estimated gestational age underwent laparoscopic cholecystectomy for symptomatic cholelithiasis or acute cholecystitis between March and September 1991. RESULTS: No complications occurred, and the postoperative courses of all patients were unremarkable. Four patients have been delivered of healthy babies, and the fifth patient is still pregnant at the time of this report. CONCLUSIONS: Laparoscopic cholecystectomy appears to be a safe treatment for selected patients with symptomatic biliary tract disease during pregnancy. Further study is warranted to determine its proper role in managing this difficult clinical problem. PMID- 1440238 TI - Lymphatic and venous examination of the ulcerated leg: a preliminary report. AB - BACKGROUND: It has been widely accepted that deep venous thrombosis and venous incompetence initiate a series of events resulting in various ulcerations. The role of the lymphatic system in the progression of these events has not been extensively studied. METHODS: Twenty-three patients with nonarterial ulcerations of the legs were examined by phlebography and lymphangiography. All had recurrent ulcerations associated with nonpitting edema, brawny induration, and dermatitis characteristic of the postphlebitic syndrome. Arterial circulation was normal in all patients. RESULTS: Phlebographic abnormalities found were the presence of communicating vein incompetence in all 23 patients, varicose veins in six, and deep venous occlusion in one. Lymphatic abnormalities were also present in all patients. Extravasation in the area of the ulcer was seen in eight patients, dermal backflow in six, tortuosity and irregularity of the channels in four, and retention of contrast agent for more than 24 hours in seven. CONCLUSIONS: Significant abnormalities of the lymphatic system exist in patients with leg ulcers caused by the postthrombotic syndrome. PMID- 1440237 TI - Granulocyte oxidative activity after thermal injury. AB - BACKGROUND: Alterations in granulocyte function after thermal injury have been described. We have serially studied the level of granulocyte cytosolic peroxidase activity in 23 thermally injured patients during the first 6 weeks after injury. The patients' mean age and burn size were 35.1 +/- 15.7 years and 41.6% +/- 16.8% (range, 18% to 88%), respectively. Fourteen patients had concomitant inhalation injury, and the overall mortality rate was 4.3%. METHODS: Purified granulocytes were obtained from peripheral blood after red cell lysis and Ficoll-Hypaque (Pharmacia Inc., Piscataway, N.J.) gradient separation. Cells were loaded with dichlorofluorescin diacetate, and baseline fluorescence was measured by flow cytometry. After phorbol myristate acetate stimulation, fluorescence was measured again. Cells from unburned normal subjects were used as daily controls. RESULTS: The data are expressed as percent of stimulated control granulocyte fluorescence. Unstimulated patient granulocytes demonstrated a significantly higher baseline activity than did unstimulated controls (22.9% vs 15.4%; p < 0.05). Mean fluorescence from stimulated granulocytes was 114% of the control values (p < 0.05). CONCLUSIONS: Granulocytes from thermally injured patients exhibited a baseline increase in cytosolic oxidase activity, suggesting in vivo activation and a greater than normal oxidase activity after in vitro stimulation. PMID- 1440239 TI - Modified anoabdominal rectal resection and colonic J-pouch anal anastomosis for lower rectal carcinoma: preliminary report. AB - BACKGROUND: There has recently been increasing interest in coloanal reconstruction after proctectomy for low rectal carcinoma. We describe here our pilot experience with seven patients undergoing modified anoabdominal resection of the rectum and a colonic J-pouch anal anastomosis. METHODS: The procedure varied according to the extent of internal anal sphincter (IAS) resection (type a, partial resection of the upper IAS; type b, circumferential resection of the upper IAS; type c, partial preservation of the lower IAS; and type d, total resection of the IAS). RESULTS: None of the patients had incontinence, but preservation of the lower half of the IAS (types a and b) showed functional superiority over more extensive IAS resection (types c and d). Only patients who underwent types c and d resection needed medications to reduce stool frequency. CONCLUSIONS: Our results suggest that the lower half of the IAS has a more important role than the upper half in the control of defecation. Total resection of the IAS did not sacrifice continence, but preservation of at least the lower IAS resulted in a better quality of life. Careful patient selection is needed when considering the use of these procedures for tumors in the lowest part of the rectum. PMID- 1440240 TI - Adrenal scintigraphy of well-differentiated (functioning) adrenocortical carcinomas: potential surgical pitfalls. AB - Adrenal scintigraphy with 131I-6 beta-iodomethylnorcholesterol (NP-59) has been widely used to evaluate adrenal cortical tumors during the past 20 years. Unilateral visualization on the side of an adrenal tumor has been considered diagnostic of a benign adrenocortical adenoma in the patient with Cushing's syndrome. Bilateral nonvisualization of the adrenal glands in the presence of Cushing's syndrome is considered diagnostic of adrenocortical carcinoma (ACC). ACCs characteristically are unable to incorporate enough NP-59 to be visualized on NP-59 adrenal scintigraphy. Two patients with well-differentiated cortisol secreting ACCs, in which the primary tumor or subsequent metastases demonstrated intense uptake (visualization) on NP-59 scans are reported here. As a result of these findings on NP-59 adrenal scintigraphy, the lesions were initially misinterpreted to represent benign disease. In each patient the operative approach selected, based on the interpretation of the NP-59 scan, was inappropriate for the management of the respective adrenal neoplasm or its metastasis. A review of the literature reveals 16 other cases of either ACC or their metastases that were visualized with adrenal scintigraphy. Ninety percent of these cases were associated with adrenocortical hormone hypersecretion. It is concluded that in the presence of Cushing's syndrome or another adrenocortical hormone excess state, unilateral visualization of an adrenal tumor on NP-59 scintigraphy cannot be interpreted to represent uniformly benign disease. PMID- 1440241 TI - Surgery for malignant obstructive jaundice: analysis of mortality. AB - Surgery on patients with malignant obstructive jaundice carries formidable morbidity and mortality rates. Clinical records of 120 consecutive patients who had a serum total bilirubin levels of 100 mumol/L or greater before exploration were analyzed retrospectively to provide guidelines for better management. Although most patients underwent bilienteric bypass to either the extrahepatic (n = 45) or intrahepatic ductal system (n = 28), resection was possible in 32 (26.7%). Complications developed in 42 patients (35%), among whome 12 (10%) required reexploration and 32 (26.7%) died within the same hospitalization. Identification of risk factors associated with hospital deaths after surgery was conducted on 84 of the 120 (group A) patients randomly selected from the entire study period. Based on multivariate analysis, age greater than 65 years, a raised serum aspartate transaminase value greater than 90 IU, and serum urea level greater than 7 mmol/L before surgery were the risk factors selected from 39 different clinical (n = 6), laboratory (n = 26), and operative (n = 7) parameters studied. The predictive value was validated in the remaining 36 patients (group B), and a high-risk patient population had been isolated. Because both serum urea and aspartate transaminase values correlated significantly with the necessity of urgent exploration, aggressive nonoperative treatment should be used to control the emergency. Alternative therapeutic options or perioperative management should be considered for the selected high-risk patients before definitive surgical biliary decompression. PMID- 1440242 TI - Spontaneous rupture and functional state of the esophagus. AB - Esophageal function was investigated after 1 to 8 years in five consecutive patients surviving spontaneous esophageal rupture (Boerhaave's syndrome) and treated by suturation. Only one patient was symptom free and had almost normal esophageal function as judged by manometry, 24-hour pH monitoring, endoscopy, and barium swallow. In the other four patients reflux symptoms and a severe functional disturbance of the esophagus were observed. In four patients the manometry revealed a lack of propulsive peristaltic movements and esophageal muscular incoordination (particularly in the upper part of the esophagus) closely mimicking those seen in the nonspecific esophageal motility disorder. In 24-hour intraesophageal pH monitoring a pathologic gastroesophageal reflux with long lasting single reflux periods was observed, suggesting poor esophageal clearance. Also endoscopic and histologic signs of reflux esophagitis were seen in the same four patients. In contrast, lower esophageal sphincter pressure was normal in all five survivors. It is concluded that patients with spontaneous esophageal rupture have a severe disturbance of esophageal motility. The concomitant reflux esophagitis may be caused primarily by the esophageal motility disturbance, which may also contribute to the origin of the rupture. PMID- 1440243 TI - Conventional versus high-porosity polytetrafluoroethylene grafts: clinical evaluation. AB - In baboons, nonreinforced (unwrapped) 60 microns internodal distance polytetrafluoroethylene grafts form a complete endothelial lining within 2 weeks by capillary ingrowth through the wall. Smooth muscle cells then grow under the endothelium and proliferate to form a complete neointima. To determine if spontaneous endothelialization of these grafts can also occur in humans, 10 above knee femoropopliteal grafts composed of equal lengths of 60 and 30 microns polytetrafluoroethylene were placed in eight patients. These grafts were reinforced (wrapped) for human use. Because biopsy of the grafts was not possible, endothelialization was assessed noninvasively by 111In-labeled platelet imaging 1 week and 3 months after surgery. There was no difference in indium uptake between 60 and 30 microns segments at either time. Histologic sections were available from 60 microns segments of two patients who underwent operation for graft thrombosis. Capillary ingrowth was seen in these grafts, but it rarely extended more than half the distance from the outside of the graft to the lumen. Smooth muscle cells were not seen on the flow surface, indicating that a neointima had not formed. These findings demonstrate that capillary ingrowth can occur in 60 microns grafts in humans but does not produce an endothelial lining. The failure to endothelialize is perhaps a result of inadequacy of angiogenesis in adult humans or retardation of capillary ingrowth by the reinforcing wrap. PMID- 1440244 TI - Burn edema is accentuated by a moderate smoke inhalation injury in sheep. AB - We determined the lung and systemic response of a moderate smoke inhalation injury combined with a 15% total body surface third-degree burn compared with a burn alone and inhalation alone. Adult sheep were prepared with chronic lung and bilateral prefemoral soft tissue lymph fistula. The burn was confined to one side. Physiologic parameters, lymph flow (QL), and lymph/plasma protein ratio were monitored. Oxidant changes were measured as lipid peroxidation by circulating and lymph-conjugated dienes and lung tissue malondialdehyde. Animals were resuscitated with lactated Ringer's solution during the 24-hour study period to restore and maintain vascular filling pressures and cardiac index. We found net 24-hour fluid balance for burn-inhalation injuries to be 4.1 +/- 1.2 L compared with burn alone of 2.9 +/- 0.9 L and inhalation alone of 2.4 +/- 0.5 L, a significant difference. Protein-rich burn tissue QL increased by fivefold to sixfold with burn alone compared with more than tenfold with burn-inhalation injury. A twofold increase in both lung and nonburn soft tissue QL was also seen in the combined injury not seen with burn alone. Arterial blood gases decreased only at 12 hours. Plasma conjugated dienes were increased in all groups, whereas burn lymph values were increased only in combined insult. In addition, lung malondialdehyde content at 24 hours was 155 +/- 11 nmol/gm with burn-inhalation injury compared with 62 +/- 8 nmol/L for burn alone, 55 +/- 9 nmol/L in inhalation alone, and 45 +/- 4 nmol/L for controls. However, no alveolar flooding was noted in any group. We conclude that a modest smoke inhalation (carboxyhemoglobin of 25%) added to a 15% total body surface burn markedly increases the degree of burn edema, as well as nonburn soft tissue and lung QL, compared with burn alone, indicating increased plasma to interstitial fluid transport in these tissues as well. Increased burn tissue lipid peroxidation products corresponded with the increased burn fluid losses. The increased lung lipid peroxidation also indicates further lung oxidant activity as well. PMID- 1440245 TI - Jejunal versus ileal segmental allografts in the dog: comparison of immunologic and functional results. AB - Segmental small-bowel grafts have been advocated as a means of reducing the incidence of rejection and graft-versus-host disease in small-bowel transplant recipients. This study compared the results achieved with heterotopic segmental allografts of the jejunum and the ileum that used 120 cm Thiry-Vella loops in a dog model. Immunosuppressive therapy consisted of 25 mg cyclosporine/kg/day. Results were monitored by histologic examinations, function tests (maltose and xylose absorption), and brush-border enzyme assays. Thirty-three dogs were randomized for use as a donor (n = 11) or recipient of a jejunal allograft (n = 11) or an ileal allograft (n = 11). Eight allografts were technical failures and were excluded from analysis. Fourteen allografts were successful (eight ileal, six jejunal). No case of graft-versus-host disease was observed. Six allografts (42.5%, three jejunal [50%] and three ileal [37.5%]) were rejected during the first 3 months (not statistically significant). Eight allografts (five ileal, three jejunal) were tolerated for up to 3 months and were removed. Two ileal and two jejunal allografts appeared grossly normal at surgical removal, but two ileal and one jejunal allografts exhibited signs of chronic rejection, and one ileal allograft showed advanced rejection. The jejunal and ileal allografts had similar clinical courses, as were revealed by immunologic reactions and functional parameters. We conclude that there is no major difference between jejunal allografts and ileal allografts in the dog. PMID- 1440246 TI - Meticulously restored lumina of injured veins remain patent. AB - We report our experience with 38 major venous injury repairs in 37 patients between January 1981 and December 1989. The injuries were caused by gunshot (n = 27), shotgun (n = 3), knife (n = 5), blunt trauma (n = 1), and dog bite (n = 1). These involved 27 femoral, 10 popliteal, and one brachial veins. Thirty patients had associated major arterial injuries and seven had major long bone fractures. Retrospective analysis yielded two groups. Group I consisted of 17 patients who underwent meticulous restoration of venous lumina ensured by intraoperative postreconstruction venography (IPV) in all patients. Two of these required revision on the basis of IPV findings. Late patency of venous repair was confirmed by postoperative venography (n = 10) or duplex scans (n = 7). All 17 venous repairs were patent (100%). In group II none of the 20 patients (21 veins) underwent IPV. Fifteen of the 20 patients underwent venography and five patients (six veins) underwent duplex scanning after surgery. Eight veins were occluded and 13 (62%) were patent. The difference in patency rates of venous repair between groups I and II was significant (p = 0.02). Three (37.5%) of eight patients with occluded venous repair required delayed fasciotomy, but only 1 (3.4%) of 29 limbs (30 veins) with patent lumina required fasciotomy (p = 0.03). We conclude that meticulous restoration to normal-caliber venous lumina, confirmed by IPV, can achieve high patency and low morbidity rates. PMID- 1440247 TI - Adenosine triphosphate-magnesium chloride in radiation injury. AB - Although adenosine triphosphate-magnesium chloride (ATP-MgCl2) has demonstrated cytoprotective effects in a variety of adverse pathophysiologic conditions, its ability to alter radiation injury is unknown. The purpose of this study, therefore, was to assess the effects of ATP-MgCl2 on colorectal radiation injury after preoperative pelvic radiotherapy. Mixed-breed pigs (n = 36) received 4250 cGy preoperative external-beam pelvic radiotherapy (350 cGy fractions three times per week for 4 weeks). During radiotherapy, animals were randomly assigned to one of three treatment groups: (1) intravenous infusions of normal saline during radiotherapy, (2) intravenous ATP-MgCl2 (30 mumol/kg) during radiotherapy, or (3) intravenous ATP-MgCl2 (60 mumol/kg) during each radiotherapy session. After completion of radiotherapy and a 4-week rest period, animals underwent colorectal resection by either the two-layer hand-sewn (n = 18) or stapled end-to-end anastomosis technique (n = 18). Laser Doppler velocimetric readings were obtained to assess mural colonic blood flow after completion of anastomosis. A second laparotomy on postoperative day 5 or 11 was done to examine the following anastomotic parameters: (1) repeat laser Doppler velocimetry, (2) gross inflammatory scoring, (3) bursting pressure, (4) preoperative barium enema to identify leak or stenosis, (5) analysis of anastomotic hydroxyproline content, and (6) incidence of cutaneous injury in the radiation portals. ATP-MgCl2 administered intravenously at 60 mumol/kg led to (1) diminished colorectal seromuscular ischemia evidenced by laser Doppler velocimetric readings, (2) decreased skin and subcutaneous tissue injury in the treatment portals, (3) significantly decreased perianastomotic inflammatory reaction, and (4) increased early hydroxyproline content. There was no significant difference in the incidence of leakage or stenosis between the study groups, nor was the anastomotic bursting strength significantly different between the treatment groups. Therefore the administration of ATP-MgCl2 (60 mumol/kg) appears to offer significant cytoprotection from preoperative pelvic radiation therapy. PMID- 1440248 TI - Physical and biologic impermeability of intestinal sutures in the first twenty four hours after operations on the gastrointestinal tract. AB - The author has substantiated a concept that in the general notion of the impermeability of intestinal sutures, it is necessary to distinguish between physical impermeability (imperviousness of sutures to liquids and gases) and biologic impermeability (imperviousness of sutures to microbes and toxins). It was established in experiments on 165 dogs that infection that invaded peritoneum during operation disappeared from the peritoneal cavity within an hour of small bowel and stomach surgery and within 1 1/2 hours of colon surgery. Then a period of sterility of peritoneum was observed, which lasted for 8 to 9 hours after operations on the stomach and the small bowel (p = 0.01) and for 4 to 7 hours after operations on the colon (p = 0.01). In the following hours the peritoneal cavity was infected through physically hermetic intestinal sutures. At the end of 24 hours the peritoneum of operated organs showed the presence of 10(4) to 10(6) intestinal microbes. Greater omentum, bowel loops, and their mesentery adhered to the suture in response to the infection through the suture. Complete covering of the suture with adjacent viscera prevented infection of the peritoneal cavity through the suture. The author suggests a well-grounded concept of the leading role of infection through a physically hermetic intestinal suture in the development of postoperative peritonitis and peritoneal adhesions. PMID- 1440249 TI - Cesar Roux--Swiss pioneer in surgery. AB - Cesar Roux of Lausanne, Switzerland, typified the pioneers in surgery at the turn of the nineteenth century. He was inspired by his mentor Theodor Kocher of Berne and the surgeons Theodor Billroth and Richard von Volkmann. Although he is best known for the Roux-en-Y loop, the first esophagojejunostomy and the first adrenalectomy are also evidence of his innovative approach to operative surgery. Despite his many contributions and honors he remained a surgeon in the field. His exemplary career is recalled here. PMID- 1440250 TI - Visceral infarction caused by cocaine abuse: a case report. AB - Cocaine abuse is now known to result in a wide variety of medical illnesses. We report our experience with one patient who had abdominal pain and was found to have near-total infarction of all abdominal viscera. The cause of this and other medical complications of cocaine abuse (i.e., extreme vasoconstriction) is discussed in detail. Physicians should maintain a high index of suspicion when dealing with complaints of abdominal pain by cocaine users. PMID- 1440251 TI - Circumferential rupture of the ascending aorta in a fusiform aneurysm. AB - A case of complete circumferential rupture of the ascending aorta with massive hemorrhage into the pericardial space and around the aortic arch is described. Computed tomography was used to establish the diagnosis. Rupture occurred distal to the origin of the coronary arteries without impairment of aortic valve function, and therefore a preclotted woven Dacron graft was inserted. To the best of our knowledge, this is the first documented case of complete rupture of the ascending aorta in a fusiform aneurysm and the first report of its successful surgical treatment. PMID- 1440252 TI - Comparison between internal mammary artery and saphenous vein bypass graft. PMID- 1440253 TI - [The assessment of the functional status of patients with dilated cardiomyopathy based on the data from a spirometry-bicycle ergometry test]. PMID- 1440254 TI - [The renin-angiotensin-aldosterone system and antidiuretic hormone in chronic circulatory failure in elderly subjects]. AB - Overall 210 patients aged 60-74 years suffering from coronary heart disease associated with chronic circulatory failure, stages I, IIA and IIB, 53 patients aged 45-59 years and 20 healthy persons aged 45-74 years were examined for the renin-angiotensin-aldosterone system and antidiuretic hormone. Renin activity, the concentration of aldosterone and vasopressin in blood plasma were investigated by radioimmunoassay. In the initial stage of heart failure, the elderly persons showed up more marked renin activation in blood plasma, followed by its lowering as decompensation progressed as well as an increase in the concentration of aldosterone and vasopressin, which resulted in the progress of circulatory failure. PMID- 1440255 TI - [The clinico-morphological aspects of primary pulmonary hypertension]. AB - The authors relate the results of a clinical and post mortem examination of 12 patients who died for primary pulmonary hypertension (PPH). The clinical, x-ray, echocardiography and electrocardiography data were of the same type in all the patients. Macroscopic studies of the heart also demonstrated similar changes: the heart mass was increased because of hypertrophy of its right parts. At the same time the microscopic picture of small vessels of the lungs turned out fairly diverse. Based on these differences all the cases were divided into 3 groups: veno-occlusive disease, recurrent pulmonary thromboembolism, plexogenic pulmonary arteriopathy. However, certain differences were noted inside the groups either. It is therefore assumed that PPH is a collective notion, uniting different alterations in small pulmonary vessels, that lead to a considerable rise of pressure in the pulmonary artery. PMID- 1440256 TI - [The prognosis of the accelerated progression of chronic glomerulonephritis]. AB - Based on the data of the 20-year follow-up of 146 patients suffering from intracapillary chronic glomerulonephritis (CGN) verified with the aid of nephrobiopsy, the conclusion was made about the necessity of distinguishing rapid progressing CGN. In such pattern of CGN, chronic renal failure may occur for up to 5 years since the disease onset. A significant relationship was established between the incidence of rapid-progressing CGN and the morphological and clinical types as well as tubulointerstitial alterations. The clinical types included the active and inactive nephritic, nephrotic and nephrotic-hypertonic types. A regressive analysis made according to the Cox method permitted one to establish that the clinical type of CGN is the most reliable factor of predicting rapid progressing disease. PMID- 1440257 TI - [Diabetes mellitus and pregnancy]. PMID- 1440258 TI - [The comparative clinico-morphological characteristics of the regional circulation of the parotid and labial salivary glands in Sjogren's disease and chronic parenchymatous parotitis]. PMID- 1440259 TI - [The main trends in the training of medical college students in clinical departments in the propagandizing of a healthy life style]. AB - Popularization of the healthy way of life (HWL) at the medical institutes is a crucial problem, since on the one hand, the medical institute is to train good specialists in terms of their own health and, on the other hand, these specialists are to popularize the HWL among the community. The paper is a summary of the experience of 10 clinical departments of the Vladivostok Medical Institute, gained with popularization of the HWL. The purpose lies in the training of the specialists in the methodology and techniques by which the HWL is to be introduced in the consciousness of the community. The realization of the purpose involves the use of conventional and original methodological approaches to the organization of the training and educational process and their differentiation at certain stages. The program and plan of the training include the use of both required and facultative forms of the training, active participation of the students in carrying out health measures among the community. PMID- 1440260 TI - [Pneumonias in the aged--their clinical picture and treatment]. PMID- 1440261 TI - [Experience in the combined treatment of different clinical forms of chronic bronchitis with new phytotherapeutic mixtures]. AB - As many as 68 patients suffering from chronic bronchitis (CB) were subjected to combined treatment by new mixtures of medicinal herbs given per os and by inhalation. Administration of the first (antiseptic) or the second (broncholytic) mixture was determined by the clinical variant of CB. In 81% of cases, the method produced a beneficial effect, contributing to the shortening of the times of the patients' treatment in the hospital. The long-term results were also positive, allowing the simultaneous use of the phytotherapeutic mixtures per os and by inhalation in the treatment of CB patients. PMID- 1440262 TI - [Cough]. PMID- 1440263 TI - [Prolonged fever as the leading symptom of granulomatous giant-cell arteritis]. PMID- 1440264 TI - [Wissler's subsepsis allergica as a manifestation of drug allergy]. PMID- 1440265 TI - [The role of the endothelial cell in immunopathology]. PMID- 1440266 TI - [The role of computed spirometry in the epidemiological study of respiratory symptoms]. AB - An epidemiological study was made of a random representative sample of men and women aged 25-64 years. There were 167 men and 306 women. In order to compare forced expiration in persons with different combinations of respiratory symptoms, potentialities of the use of the forced midexpiratory flow 25-75% together with the FEVC, FEV1, FEV1/FEVC were examined. Among the flow parameters, the forced midexpiratory flow has the least variability, which permits using it for diagnosis of obstructive disorders of lung ventilatory function. The studies revealed qualitative peculiarities in the changes of the spirography readings among men and women. As compared to the examinees without respiratory symptoms, men with cough and sputum manifested a decrease in the parameters characteristic of mixed changes in lung ventilatory function with the predominance of obstructive alterations in chronic bronchitis. The degree of obstructive disorders was higher than in women showing the analogous symptoms. As compared to the examinees without respiratory symptoms, women suffering from chronic bronchitis were marked by lower values of the volumetric parameters, without any signs of forced expiration deceleration. PMID- 1440267 TI - [Monocyte functional activity and nonspecific antiviral cellular resistance in a group at high risk for developing acute pneumonia]. AB - Overall 132 patients at greater risk for pneumonia were examined for functional activity of monocytes and antiviral cellular resistance according to the status of intracellular viremia in monocytes and lymphocytes. The control group included 46 healthy men. Proneness to pneumonia was discovered to be related to abnormal function of mononuclear phagocytes and a decrease of antiviral cellular resistance. The conclusion is made about the necessity of the control over functional activity of monocytes, viremia in immunocompetent cells and advisability of carrying out immunomodulatory and antiviral therapy. PMID- 1440268 TI - [The metabolism of eicosanoids, glucocorticoids and cyclic nucleotides in young people with acute pneumonia]. AB - An investigation into the pathogenesis of acute pneumonia in 37 young men made it possible to ascertain the role of arachidonic acid metabolites and hormonal regulation in the pathogenesis of the inflammatory reaction in acute bacterial pneumonia. At the initial stage of inflammation, invasion of the infectious agent leads to phagocytosis activation, stimulates the output of immunoglobulins belonging to different classes, which, binding antigens, form immune complexes influencing the output of biologically active substances. This is accompanied by the destruction of pulmonary tissue, release of lipid peroxidation radicals and proteinases, by the enhancement of arachidonic acid degradation under the destructive action on the membranes of phospholipase A2 cells to form prostaglandins participating in the changes in the tone of bronchi, pulmonary vessels and affecting blood coagulation. Activation of the hypophyseo-adrenal system leads to the attenuation of the effects produced by biologically active substances and exerts varying actions in the acute and convalescence periods. The data obtained stress an important role played by metabolic functions of the lungs in the integrative connections of all the systems of the body maintaining homeostasis in pneumonia and the main function of the lungs, namely ventilation. PMID- 1440269 TI - [The efficacy of using the Soviet antibiotic rifamethoprim in treating acute bacterial pneumonias and chronic bronchitis]. AB - Rifametoprim (600 mg/day) was given to 64 patients with acute bacterial pneumonia, acute bronchitis and exacerbation of chronic bronchitis. 201 (83.4%) out of 241 isolates were sensitive to the action of the antibiotic. The treatment turned out effective in 84.4% of cases. PMID- 1440270 TI - [The clinical efficacy of treating patients with acute pneumonias by using drug and quantum correction of the lipid peroxidation-antioxidant system]. AB - The authors describe the status of lipid peroxidation (diene conjugates and malonic dialdehyde) and the endogenous antioxidant enzyme superoxide dismutase in the course of the treatment of patients with acute focal pneumonia by means of the use of transthoracic intrapulmonary injections of unithiol and autologous ultraviolet blood radiation (AUVBR). Three groups of patients were entered into the study. The first group included 64 patients who were given transthoracic intrapulmonary injections of unithiol, the second group 58 patients who received 5-7 sessions of AUVBR, in the third group, 52 patients were given transthoracic intrapulmonary injections of unithiol coupled with 3-5 sessions of AUVBR. The control group was made up of 40 patients given intravenous unithiol injections in routine therapeutic doses. The results of the treatment evidence that combined correction of lipid peroxidation carried out in the third group patients was most effective. As regards the times, the positive dynamics of lipid peroxidation and superoxide dismutase activity correlated with the clinical, biochemical and x-ray improvement. Therefore the method of correction in question is a pathogenetically based approach, permitting one to enhance the clinical efficacy of the treatment of patients suffering from acute focal pneumonias and to reduce the times of their stay in the hospital by 5-7 days, on the average. PMID- 1440271 TI - [Viral infection in pulmonology]. PMID- 1440272 TI - [The causes of prolonged fever in patients with infiltrative lung processes]. AB - The authors analyze the causes of lingering fever in patients with pulmonary infiltrations. The given phenomenon is most often caused by pneumonias provoked by unusual causative agents (Legionella, Rickettsia, Mycoplasma). In such cases, administration of erythromycin is effective. In rare cases, lingering fever is induced by blocked pulmonary suppurations, pleural exudates in pneumonia patients, and infiltrative tuberculosis. Besides, there were cases, in which fever was of drug etiology. PMID- 1440273 TI - [The prognosis of the outcome of the inflammatory process in chronic bronchitis]. AB - The authors relate the data on the leading part fibrosoformation plays in the disease outcome in patients with certain pulmonary chronic illnesses. The levels of free and bound hydroxyproline and hyaluronidase activity served as diagnostic criteria for processes of fibrosoformation. Based on the data obtained a method of predicting chronic bronchitis (CB) was devised. Thus, the two-fold rise of hyaluronidase activity as compared to normal and the index of fibrosing (the ratio of free to bound hydroxyproline) exceeding 1 suggest an unfavourable course of CB accompanied by the enhancement of fibrosoformation. Meanwhile if hyaluronidase activity increases 2-fold and more and the index of fibrosing is less than 1, the prognosis of inflammatory process may be favourable. Based on the clinical data, the significance of prognosis was proved in 93% of cases. PMID- 1440274 TI - [The contractile capacity of the myocardium in patients with chronic obstructive bronchitis]. AB - As many as 123 patients with chronic obstructive bronchitis (COB) were examined. Myocardial contractility was estimated by echocardiography. The data obtained indicate that in COB patients, the contractility of the right and left heart is disordered. The level of systolic pressure in the pulmonary artery did not exceed 45 mm Hg in COB patients and cannot be the cause of the overload of the right heart. The decrease of left ventricular contractility is not associated with the concomitant pathology of the cardiovascular system. The causes of myocardial contractility disorders in COB patients remain unclear. PMID- 1440275 TI - [The activity of lipid peroxidation and proteolysis in assessing the stability of the course and the prognosis of ischemic heart disease in patients with chronic bronchitis]. AB - In combination of coronary heart disease with chronic obstructive bronchitis observed in 57 patients there appeared hyperactivity of lipid peroxidation and suppression of lipid antioxidant abilities. In aggravated chronic bronchitis, lipid peroxidation intensified still more, starting the chain of biochemical reactions which entailed further imbalance and inhibition of the antioxidant and proteolysis systems. This suggests the conclusion on the validity of introduction of antioxidants and proteolytic inhibitors into complex therapy of such patients. PMID- 1440276 TI - [Hypoxic stimulation and inspiratory resistive training in the rehabilitation of patients with chronic bronchitis]. AB - A study was made of the efficacy of normobaric hypoxic stimulation (NHOS) and inspiratory resistive training (IRT) in multimodality treatment and rehabilitation of patients suffering from chronic obstructive bronchitis. The results were estimated by means of exercise tests and by stimulation electromyography of the diaphragm (SEMGD). The use of NHOS and IRT in multimodality treatment of the given group patients was found to give rise to a more complete physical rehabilitation of the patients, whereas the application of SEMGD is an effective approach to the control of sessions and courses of NHOS and IRT. Besides, the use of the latter method also permits choosing the intensity of the action of the treatment methods in question on the body, particularly on the diaphragm muscle. PMID- 1440277 TI - [Asthmatic bronchitis as the first manifestation of secondary immunodeficiency in hereditary enzymopathy in women]. AB - The characteristics of nonspecific immunity were studied on an outpatient material of 80 non-smoking women aged 38-60 years, with manifestations of hereditary primary enzymopathy (hyperoxaluria syndrome). Hyperoxaluria was shown to be related to immunologic imbalance of some components of nonspecific resistance by the cellular and humoral type. In addition to biochemical differences, the group of patients with prognostically favourable chronic asthmatic bronchitis have got immunologic differences with the alternative group. PMID- 1440278 TI - [The generation of active forms of oxygen by the blood leukocytes, lipid peroxidation and antiperoxide protection in bronchial asthma patients]. AB - A study was made of the generation of active forms of oxygen by leukocytes, of free radical lipid peroxidation and antiperoxide activity (APA) in 52 bronchial asthma (BA) patients depending on the disease phase and of a possibility of their correction with antioxidants. In BA exacerbation, chemiluminescence of leukocytes (CL) and plasma content of malonic dialdehyde (MDA) increase whereas plasma APA reduces as compared to the control. During remission, CL and plasma content of MDA decrease but do not reach normal. Simultaneously one can see a tendency toward plasma APA reduction as compared with the phase of exacerbation. BA patients who received antioxidants in addition to the conventional therapy demonstrated a more pronounced lowering of CL and plasma MDA content than those given the conventional therapy alone. The data obtained attest to the activation of free radical oxygen and lipid processes and to inhibition of plasma APA in BA, providing evidence in favour of including antioxidants in combined therapy of BA. PMID- 1440279 TI - [The effect of theophylline on purine receptor function in bronchial asthma patients]. AB - A study was made of purine receptors (PR) in healthy subjects and bronchial asthma (BA) patients before and after theophylline (TP) treatment. BA patients demonstrated a significant lowering of the binding sites of A2PR and a tendency toward the rise of the number of A1PR on peripheral blood lymphocytes as compared to the healthy subjects. As a result of TP therapy for 3 weeks, the number of A2PR increased in 69% and the number of A1PR fell in 50% of the patients. The efficacy of TP pharmacotherapy depended significantly on the increment of the binding sites of A2PR. The growth of the number of A2PR was recorded in the groups of patients with a beneficial and satisfactory effect of the treatment. PMID- 1440280 TI - [The effect of a single dose of nifedipine, intal, sodium thiosulfate and Essentiale on the blood level of calcium, hydroperoxides, thiol compounds and prostaglandins in bronchial asthma patients]. AB - A study was made of the impact of a single intake of nifedipine, intal, sodium thiosulfate and essentiale on respiratory function, the blood content of ionized calcium, total calcium, hydroperoxides, total and non-protein thiol groups, and prostaglandins in bronchial asthma patients. All the drugs exerted an antioxidant action, which is supported by the lowering of the content of hydroperoxides after their administration and by an increase of the content of thiol groups. A rise of the level of PGE and a considerable reduction of blood serum PGF2 alpha, most remarkable after essentiale administration were also noted. In patients given nifedipine in a dose of 20 mg, an insignificant broncholytic effect was recorded in more than half the cases. An appreciable rise of blood ionized calcium was seen in all the cases. Obviously, this is a direct consequence of its limited supply to the cells via calcium channels. In contrast to patients who received other drugs, those given intal demonstrated the lowering of blood serum ionized calcium and the growth of the content of bound calcium, which may be accounted for the transformation of ionized calcium to the bound condition. PMID- 1440281 TI - [An evaluation of the efficacy of Beclometh in bronchial asthma patients]. AB - Fifteen bronchial asthma patients were followed-up for 6 months. They were administered beclomet-250 in a daily dose 1000 micrograms. The patients' clinical status was characterized by positive changes, ventilation function of the lungs improved. The drug was discovered to produce no suppressive action on adrenal function. Besides, the patients did not develop oropharyngeal candidiasis. PMID- 1440282 TI - [The use of transbronchial ECG leads for the early detection of hemodynamic disorders in the lesser circulation in chronic nonspecific lung diseases. 1]. AB - Increased resistance of pulmonary blood vessels is of basic significance in the development of pulmonary hypertension. Atrial complex of transbronchial ECG leads, recorded with a special electrode, reveals early disorders of pulmonary circulation and consequent hyperfunction of the right atrium. Adequate task for ECG is registration of changes in myocardial biopotentials rather than quantitative assessment of pressure in the pulmonary artery. Combined bronchoscopy and electrocardiography enhance their potentialities and can be used to identify patients, who are likely to develop pulmonary hypertension. PMID- 1440283 TI - [The problems of the clinical integration of pulmonology and other therapeutic disciplines (the internist pulmonologist--myth or reality?)]. PMID- 1440284 TI - [The function of the collateral bed in patients with ischemic heart disease and isolated occlusion of the anterior descending branch of the left coronary artery]. AB - To study the collateral bed, 39 coronary heart disease patients with isolated occlusion of the anterior descending artery without a history of large-focal myocardial infarction were examined. All the patients were subjected to coronary angiography and left ventriculography. Based on an analysis of left ventricular myocardial contractility, the patients were distributed into 2 groups. The first group included 16 patients without disorders of local contractility of the left ventricular myocardium, the second one 23 patients with derangement of local contractility of the left ventricular myocardium. The conclusion is made that in patients suffering from stable angina pectoris with isolated occlusion of the anterior descending artery without a history of large-focal myocardial infarction, exclusively intersystemic collateralization of the vessel via the conal artery (or the conal branch of the right coronary artery) is most favourable from the standpoint of the maintenance of myocardial contractility. PMID- 1440285 TI - [Arterial hypertension as a prognostic factor in the course of ischemic heart disease]. AB - Overall 235 patients with a history of uncomplicated myocardial infarction were examined. Of these, in 79 patients (33%), myocardial infarction developed in the presence of arterial hypertension. To predict the efficacy of rehabilitation treatment, postinfarction angina pectoris, arterial hypertension, the size and localization of the injury, the status of the coronary and myocardial reserves were taken into consideration. The data obtained confirmed the prognostic significance of arterial hypertension in the estimation of the efficacy of rehabilitation therapy. Arterial hypertension contributes to an unfavourable course of CHD and to a decrease of the work fitness of the patients who suffered myocardial infarction. Estimating the long-term efficacy of rehabilitation treatment, it is necessary to bear in mind not only the coronary reserves, but also the myocardial reserves, its integral index--the total ejection fraction and regional myocardial contractility. PMID- 1440286 TI - [Experience with the use of streptokinase in acute myocardial infarct at the prehospital stage]. AB - The authors analyze the experience gained with the systemic thrombolytic therapy (STLT) at the prehospital stage of the treatment of acute myocardial infarction by specialized emergency cardiological teams. The screening of patients to be given STLT was performed via the remote diagnostic center. STLT was provided to 43 patients who were given intravenous injections of 500,000 PU streptokinase (Avalizin, GDR) for 15-30 minutes. The control group included 16 patients given standard therapy. After STLT 62.8% of the patients demonstrated moderate arterial hypotension, which could readily be corrected. Myocardial reperfusion after STLT manifested by rapid removal of the painful syndrome, characteristic dynamics of ECT, and by the appearance of specific reperfusion disorders of rhythm and conduction. The accelerated idioventricular rhythm, ventricular premature heart beat and A-V rhythm of the junction were recorded most frequently. The indicated rhythm disorders were removed readily enough. It is recommended that STLT may be carried out at the prehospital stage of AMI treatment by the cardiological emergency teams, which is likely to appreciably enhance the efficacy of the given therapy form. PMID- 1440287 TI - [The physical and psychological rehabilitation of women who have had a myocardial infarct]. AB - The study was performed of the effect of bicycle exercise and occupational therapy (embroidery, knitting, sewing, drawing, etc.) on physical and psychological status of postmyocardial infarction females at the in-hospital stage of rehabilitation. It was found that occupational therapy improved the psychological status and life quality, whereas low-intensity physical training increased performance status in relevant women. PMID- 1440288 TI - [The clinico-electrocardiographic classification of the early ventricular repolarization syndrome]. AB - Based on an analysis of 4980 ECGs of patients, the authors could distinguish and classify the clinico-electrocardiographic versions of the early ventricular repolarization syndrome (EVRS): permanent, occurring for the first time, suddenly disappearing, intermittent with a gigantic T wave; with a negative T wave, with a short-term T wave inversion, marked by the combination with Wolff-Parkinson-White syndrome, and additional chordae of the left ventricle. The clinico electrocardiographic classification of the EVRS is of paramount importance for practitioners owing to an assumption that the EVRS is not only a version of the normal ECG but also can be a marker of CHD. The authors view the EVRS as an independent version of the preexcitation syndrome along with Wolff-Parkinson White and CLK syndromes, with the manifestations of which it may combine. PMID- 1440289 TI - [Abramov's "primary myocarditis", Fiedler's myocarditis and dilated cardiomyopathy]. AB - After comparing the clinical and post mortem signs of myocarditis and dilated cardiomyopathy on the basis of correlating the reported data and own data on 28 patients with the appropriate descriptions by S. S. Abramov and A. Fiedler, the authors came to the conclusion that they had described two different diseases. S. S. Abramov had described dilated cardiomyopathy, whereas Fiedler acute diffuse myocarditis. The term Abramov-Fiedler myocarditis used in the Soviet literature does not correspond to the up-to-date classification of myocardial diseases. That is why it is required that these two concepts be separated to the benefit of the treatment. PMID- 1440290 TI - [A clinical case of Sneddon's disease]. PMID- 1440291 TI - [Panniculitis in gout]. PMID- 1440292 TI - [The benign course of extracapillary nephritis of drug-induced etiology]. PMID- 1440293 TI - [Insuloma as the cause of a hypoglycemic syndrome]. PMID- 1440294 TI - [The basic groups of modern diuretic preparations. I. The mechanisms and location of the action of diuretic preparations in the nephron. Carbonic anhydrase inhibitors. Thiazide and thiazide-like diuretics]. PMID- 1440295 TI - [The history of the creation of methods of physical diagnosis: the priority of Russian clinical internal medicine in developing methodical palpation]. PMID- 1440296 TI - [The use of stress echocardiography with dobutamine for the diagnosis of ischemic heart disease and for the detection of viable myocardium]. PMID- 1440297 TI - [The dynamics of the concentration of atrial natriuretic factor depending on changes in the arterial pressure level in patients with arterial hypertension]. AB - The purpose of the study was to explore the dynamics of the concentration of atrial natriuretic hormone (ANH) in response to changes in arterial pressure including those induced by hypertonic crisis, 7-day hypotensive monotherapy with the drugs having different action mode, and the acute test with the basic hypotensive drugs. 75 patients suffering from arterial hypertension were entered into the study. Measurements of the concentration of ANH in blood plasma were performed by radioimmunoassay with the aid of the kits manufactured by the Amersham Company (Great Britain). The activity of renin and aldosterone was determined by radioimmunoassay according to the standard technique. A strong positive correlation was revealed between the concentration of ANH and the level of both systolic and diastolic AP. A significant rise of the concentration of ANH elicited by hypertonic crisis reflects the growth of the tension of the depressor mechanisms by which AP is regulated. The lack of significant changes in the level of ANH during the acute pharmacological tests and effective continuous treatment with the hypotensive drugs attests to the existence of the complex mechanisms that regulate ANH secretion, determined not only by the level of AP. PMID- 1440298 TI - [Concomitant rheumatoid arthritis and microcrystalline arthropathies]. PMID- 1440299 TI - [The use of frequency-correlation electrocardiography on patients with left ventricular hypertrophy]. AB - The frequency correlation electrocardiogram (FCECG) was recorded in 27 patients with arterial hypertension (AH) and left ventricular hypertrophy (LVH), 8 patients with hypertrophic cardiomyopathy, 22 patients with coronary heart disease (CHD) and in 10 practically healthy volunteers. V4, V5 and V6 ECG leads were used as channel X, whereas lead II was used as channel Y. Application of V6 lead as channel X turned out most informative. The patients with AH and CHD had pathological indices in channel coherence. The patients with LVH manifested deviations in the spectrum of the amplitudes of lead II. The patients with associated LVH and relative coronary insufficiency demonstrated the unchanged FCECG like the practically healthy persons. In the given case, however, the unchanged FCECG in the above patients reflected the impairment of stimulation spreading in the left ventricular myocardium rather than the lack of its hypertrophy. PMID- 1440300 TI - [The nature of the changes in the repolarization complex of the ECG in patients with arterial hypertension and left ventricular hypertrophy]. AB - Altogether 58 patients suffering from arterial hypertension (AH) were examined. The patients with left ventricular hypertrophy (LVH) and changes in the ST-T demonstrated a high correlation between an increase of the end systolic tension (EST) and interval elongation and the minimal size of the left ventricle before mitral valve opening. These data point to the development of "high-stressful LVH" which is accompanied by a non-proportional increase of EST, subendocardial ischemia of the myocardium (changes in the ST-T) and derangement of diastolic heart function. PMID- 1440301 TI - [Fluctuations in the stenocardia threshold of patients with ischemic heart disease]. AB - In twenty-eight men (the mean age 49.3 +/- 3.2 years) with different clinical varieties of angina pectoris, analysis was made of the heart rate and the grade of ischemic depression of the ST segment, associated with anginous attacks seen during bicycle ergometry and other physical exercises in the course of daily cardiomonitoring. The data obtained indicate that in the same patient, the same grade of ischemic depression of ST was recorded despite varying heart rate. On the contrary, in spite of the same heart rate the grade of ischemic depression of the segment could vary. Dynamic coronary obstruction determined by the mechanisms of adrenergic vasoconstriction is the most probable cause of changeability of the threshold of angina pectoris in patients belonging to functional classes III-IV. The probability of fluctuations in the threshold of angina pectoris should be taken into consideration in deciding expert problems and in the assessment of the efficacy of antianginal therapy. PMID- 1440302 TI - [Left ventricular function in patients with ischemic heart disease and "critical" stenosis of one coronary artery. The data from multiphasic ventriculography]. AB - As many as 38 patients with the clinical and angiographic signs of "critical" stenosing of one coronary artery were examined. All the patients underwent coronary angiography and transvenous multiphase left ventriculography. The authors defined a complex of fairly early, "preclinical" signs of myocardial ischemia, pertaining to the energetic effectiveness of the cardiocycle, diastolic function of the left ventricle and indices of the local movement of chamber walls. It is important that these signs are recordable in minimal, clinically undetectable myocardial ischemia characterized by the lack of anginous pain, no changes in the ECG, and when the two-picture analysis, commonly used in clinical practice, provides normal results. PMID- 1440303 TI - [The expansion of the medical possibilities in timely diagnosis]. PMID- 1440304 TI - [The significance of microproteinuria for the diagnosis of kidney involvement in hypertensive disease and secondary forms of arterial hypertension]. AB - N-acetyl-beta-glucosaminidase (NAG) activity, the concentrations of microalbumin (MA) and B2-microglobulin (B2-MG) were measured in urine of 50 healthy subjects and 200 patients suffering from arterial hypertension (AH) with preserved renal function, including patients with essential hypertension (EH), stages I and II, chronic pyelonephritis (CPN), chronic glomerulonephritis (CGN) and vasorenal hypertension (VRH). The healthy subjects, the patients with stage II EH, and those with secondary forms of AH demonstrated significant differences in NAG activity in urine. A positive correlation (r = +0.53; p < 0.03) was discovered between systolic AP and NAG activity in urine of EH patients. The concentration of MA in urine of CGN and VRH patients was significantly higher than that in the healthy subjects, EH and CPN patients. The patients with CPN and VRH showed significantly higher levels of B2-MG in urine. PMID- 1440305 TI - [Renal scintigraphy with captopril in the diagnosis of renovascular hypertension]. AB - Altogether 16 patients with arterial hypertension (AH) were examined. Of these, 11 were with stenosis of renal arteries, 4 had essential hypertension (EH) and I with nephrogenous parenchymatous AH. To estimate the influence of captopril on the total and separate renal function in patients with and without stenosis of renal arteries and the possibility of the use of the given pharmacological test in the diagnosis of renovascular hypertension (RVH), all the patients underwent renal scintigraphy with 99Tc-DTPA on admission to the hospital and 1-7 days after a single intake of 25 mg captopril per os. Later on in the operated patients the results of the test were compared with the hypotensive effect of the surgery. The rate of glomerular filtration (RGF) was measured according to the Gates method. In patients with stenosis of renal arteries and EH, the total filtration renal function remained unchanged after the intake of a single dose of captopril. In patients with stenosis of renal arteries, there was a significant decrease of the RGF on the side of stenosis made for by an insignificant elevation of the RGF in the contralateral kidney, which was accompanied by an increase of asymmetry of the renograms. In patients with no hypotensive effect of the surgery, the test with captopril was negative, which supports the possibility of this test application in the diagnosis of RVH. PMID- 1440307 TI - [The diagnosis of hypertension: the tasks, difficulties and errors]. PMID- 1440306 TI - [The efficacy of nitrendipine in patients with stable arterial hypertension. The data from a cooperative study in the USSR. The Working Group for the Cooperative Study of Nitrendipine]. AB - Nitrendipine (bypress) manufactured by Bayer Company in the form of 10 and 20 mg tablets and administered in a dose of 20-40 mg/day turned out an effective antihypertensive remedy in 65% of patients with arterial hypertension largely running a mild course. The effect of nitrendipine administered in a single daily dose of 20 mg did not differ from that attained with the same dose given in two intakes. The raising of the daily dose of nitrendipine from 20 to 40 mg was associated with augmentation of the hypotensive effect in 43.8% of the patients in whom the treatment in a dose of 20 mg a day had turned out ineffective. Under the conditions of the cross-over method with the use of the reference drugs belonging to three groups of the basic antihypertensive agents (nifedipine, propranolol, hydrochlorothiazide), the hypotensive effect of nitrendipine did not differ from that produced by the drugs under comparison (according to the mean group indicators and individual assessment of the efficacy). The tolerance of nitrendipine administered in a dose of 10 mg twice a day or in a dose of 20 mg once or twice a day was satisfactory. PMID- 1440308 TI - [Arterial hypertension in the late period after the hemodynamically adequate correction of aortic coarctation]. AB - The paper is concerned with a study of arterial hypertension in the long-term periods after the resection of coarctation of aorta in 77 patients aged 6 to 35 years. The complex of the patients' examination included bicycle ergometry. Arterial hypertension was revealed in 59.7% of the patients. In 83.2%, adequate correction was performed, in 16.8%, recoarctation was suspected. The rate of the development of hypertension in the operated under 16 years depends on the grade of the systolic AP increase before the operation. In those operated on in the older age, the rate of arterial hypertension depended on the time elapsed after the operation and the age by the moment of examination. In 50% of arterial hypertension patients, the work fitness corresponds to that in healthy subjects, in 28%, it constitutes 75% of the level seen in healthy subjects, and in 22%, it is low. Indications for operation in persons under 16 years rest on the grade of the arterial pressure increase; in the older age, indications are not dependent on the arterial pressure level. PMID- 1440309 TI - [The comprehensive diagnosis of the aortic arch syndrome in nonspecific aortoarteritis]. AB - The authors provide a scheme of a comprehensive diagnosis of the aortic arch syndrome in nonspecific aortoarteritis. It includes the clinical and laboratory data together with the data on the anamnesis, angiography and ultrasound dopplerography. The derangement of the aortic arch was diagnosed in 65 (41%) out of 128 patients. There were 53 (81.5%) women and 12 (18.5%) men. The derangement of the branches of the aortic arch was most frequently (in 33.8% patients) associated with vasorenal hypertension syndrome. The use of modern research methods in combination with the clinical data and findings of objective examinations turned out fairly effective in the diagnosis of the derangement of the aortic arch in nonspecific aortoarteritis. PMID- 1440310 TI - [The efficacy of combinations of anti-arrhythmia preparations in patients with the paroxysmal form of atrial fibrillation]. AB - The efficacy of allapinin, ethacizine, ritmilen, kinilentin, obsidan and finoptin given alone and in different combinations was studied in 44 patients with paroxysmal atrial fibrillation provoked by transesophageal pacing. The use of the combinations of the drugs belonging to the first group as well of those of the first group combined with the drugs belonging to the 2nd-4th group permitted one to significantly enhance the treatment efficacy, to reduce drug doses in a lot of patients and, therefore, to minimize the rate of side effects. The data obtained promoted the choosing of the therapy algorithm to prevent paroxysms of atrial fibrillation. While designing the algorithm, account was taken of the rate of paroxysms and of the initial sinus rhythm as was of the results of estimating the comparative efficacy of the drugs under study. PMID- 1440311 TI - [The mechanisms of the development and diagnosis of myocardial infarct in septic endocarditis]. AB - Based on the clinical, instrumental and biochemical findings, out of 104 patients with septic endocarditis 11 (10.6%) were diagnosed to have myocardial infarction. It was provoked by coronary artery embolism, the covering of the coronary artery ostium by vegetation from the aortal cusp, a decrease of perfusion pressure in atherosclerosis stenosed coronary arteries because of marked insufficiency of the aortal cusp. In more than half the cases, the clinical picture of myocardial infarction was atypical, painless. Echocardiographic demonstration of the vegetations near the coronary artery ostium permits forecasting the possibility of its covering with vegetation, the threat of the occurrence of acute coronary insufficiency, which may appear an additional indication for heart valve replacement. PMID- 1440312 TI - [Acute rheumocarditis in young men]. AB - A study was made of the characteristic features of rheumocarditis in 200 young recruits. Rheumocarditis developed within the first 2-3 days since the onset of migrating polyarthritis and high fever. In many cases, it was accompanied by rhythm and conduction disorders as well as by a moderate increase of the left heart in combination with intracardiac hemodynamic disturbances. In 42 patients (21%), myocardial injury was coupled with mitral valve lesion. Injury to the pericardium was recorded in 20 patients (10%); fibrinous pericarditis was diagnosed in 15 patients, exudative pericarditis in 5 patients. Injury to all 3 heart membranes was ascertained in 5 patients (2.5%) (according to echocardiography). Thus, the clinical and instrumental manifestations of rheumocarditis made it possible to diagnose marked carditis symptoms almost in all the patients (in 96%). Unmarked carditis was only discovered in 7 patients. The above-mentioned characteristics of rheumocarditis in young men may be due to the intensity of the action of streptococcal infection on the heart structures within the first days of the disease as well as due to the action of immunopathological processes. Besides, a definite role may be played by the foregoing physical load. PMID- 1440313 TI - [The clinical aspects of the diagnosis of rheumatoid arthritis]. AB - Altogether 212 patients aged 16 to 73 years with rheumatoid arthritis (RA) lasting 3 months to 32 years were examined. Of these, 78 patients had grade I, 111 grade II, and 23 grade III disease activity. 34 patients had stage I, 76- stage II, 56--stage III, and 24--stage IV disease. In 22 patients, roentgenography failed to reveal pathology of the joints. The reference group comprised 65 patients suffering from gouty arthritis, 46 having osteoarthrosis deformans with phenomena of secondary synovitis, 30 with Bekhterev's disease, 10 with systemic lupus erythematosus, 6 with Reiter's disease, 5 with psoriatic arthropathy, and 50 with non-rheumatic diseases. When trying the diagnostic criteria for ARA (revised in 1987), criteria 1-4 and 7 were found to be most sensitive (from 88.2 to 93.8%), criteria 5 and 6 appeared most specific (100 and 98.6%, respectively). The specificity of the remaining criteria ranged from 85.4 to 96.3%. The use of the revised criteria for ARA in clinical practice was dictated by the necessity of improving RA diagnosis. PMID- 1440314 TI - [The treatment follow-up and diagnosis of drug intolerance]. PMID- 1440315 TI - [The morphofunctional parallels in arterial hypertension in patients with chronic glomerulonephritis]. AB - A study was made of the structural rearrangement of renal tissues in intravital nephrobiopsy specimens and of the functioning of the renin-angiotensin aldosterone system and kallikrein-synthetic function in patients with mesangioproliferative (MSPGN) and membranous proliferative glomerulonephritis (MPGN). The morphological changes were revealed. The patients with associated MSPGN and secondary hypertension (SH) mostly demonstrated emptying and hyalinosis of arteries, whereas those with associated MPGN and SH manifested for the most part the derangement of the tubulointerstitial structures. In patients with MPGN, the levels of total renin (TR) and inactive renin (IR) were significantly higher than in those suffering from MSPGN. This can be regarded as risk factor of earlier development of SH. In MPGN patients, the content of TR and IR as well as that of active renin (AR) did not depend on the clinical pattern of chronic glomerulonephritis. As compared to MSPGN patients with isolated urinary syndrome, those with associated MSPGN and SH had a higher AR level, which agreed well with systolic and mean arterial pressure. Apparently, the latter one is implicated in the mechanism of SH in MSPGN. In associated MPGN and SH, kallikreinuria was found to be lowest, which may be the consequence of tubulointerstitial lesions. Discoordination of the renin-angiotensin and kallikrein systems is likely to be one of the causes of earlier formation and severe course of SH in the morphological pattern under consideration. PMID- 1440316 TI - [The importance of determining the level of fibronectin in the blood plasma and urine of patients with chronic glomerulonephritis and amyloidosis]. PMID- 1440317 TI - [Crohn's disease. The problem of early diagnosis]. AB - A retrospective analysis was made of the diagnostic period of Crohn's disease as well as of x-ray and endoscopic signs in 28 patients. Three forms of the disease were distinguished: acute (pseudoappendicular), stenosing with chronic intestinal obstruction syndrome and primary chronic characterized by the triad (pains in the stomach, diarrhea, fever) or by the syndrome of malabsorption with extraintestinal manifestations. In the stenosing and primary chronic forms of Crohn's disease, a correct diagnosis was established in the majority of the patients 3-5 years after appearance of the symptoms. To improve early diagnosis of Crohn's disease, it is recommended that indications for x-ray and endoscopic examinations be extended. These examinations are indicated in all the patients with recurrent pains in the right iliac area, fever of obscure genesis and chronic diarrhea. PMID- 1440318 TI - [The optimization of the detection of tumors of the organs of the hepatobiliopancreatic area by a combination of the ultrasonic study method and of the determination of tumor markers in the blood serum]. AB - To find out new possibilities of improving the diagnosis of tumors of the hepatobiliopancreatic area, comparative assessment was made of the efficacy of ultrasonography and detection of oncomarkers (carcinoembryonic antigen and carbohydrate antigen CA-19-9) in blood serum of patients with suspected carcinoma and metastatic injury to the liver, the biliary system and pancreas. Analysis of the results has shown that echography is highly informative in the diagnosis of the given pathology type. However, in some cases, particularly in those where ultrasonography is impeded or else its results are inconclusive, it is advisable that the concentration of oncomarkers (preferably of CA-19-9) be measured additionally in blood serum, with those oncomarkers producing the highest effect in tumors of the biliary system and pancreas. PMID- 1440319 TI - [Diagnostic difficulties and errors in early stomach cancer]. AB - Difficulties that occur in the diagnosis of early gastric carcinoma (EGC) were studied on a material of 1617 prophylactic endoscopic examinations of persons who did not make any complaints of the alimentary organs and 2158 primary gastroscopies performed in accordance with the patients' complaints, results of the dispensary follow-up of 811 patients who made up a risk group, and an analysis of case reports of 183 patients in whom EGC was confirmed by surgery. The authors emphasize a high percentage of errors determined by the lack of the pathognomonic symptomatology, difficulties of interpreting the endoscopic appearance and histologic confirmation of carcinoma. To improve early diagnosis of gastric carcinoma (GC), it is recommended that every endoscopic investigation be performed with oncological apprehension, paying attention even to the minimum focal changes in the gastric mucosa and making spot biopsy of those changes. It is also advisable that a more strict approach should be exercised to the formation of risk groups, restricting them to the patients at greater risk for GC or with unrecognized GC (first revealed and poorly healing ulcers, polyps measuring over 2 cm in diameter, grade III dysplasia discovered in gastric biopsy specimens). Such patients should be placed under dispensary observation including endoscopy which is to be made in the first stage after 1, 3 and 6 months. PMID- 1440320 TI - [Hypertension and "silent" myocardial ischemia. I. The results of stress scintigraphy of the myocardium in patients]. AB - As many as 24 patients suffering from essential hypertension (EH) were examined. The patients were subjected to Holter ECG monitoring, echocardiography, coronary angiography, exercise scintigraphy of the myocardium with transesophageal pacing of the atria and the dipyridamole test. The patients manifested defects of thallium accumulation during exercise scintigraphy of the myocardium. They were transitory defects of accumulation with clearance impairment recorded in EH patients with atherosclerosis of the coronary arteries; transitory defects of accumulation without clearance impairment recorded in EH patients with the angiographically unchanged coronary arteries. In Holter ECG monitoring, the patients with a silent depression of the ST segment demonstrated transitory defects of thallium accumulation by the myocardium in all the cases during exercise scintigraphy of the myocardium. PMID- 1440321 TI - [Computed tomography and physical methods of patient study]. PMID- 1440322 TI - [Ticlid--a new development in the treatment and prevention of arterial thromboses]. PMID- 1440323 TI - [Hyperfiltration as a factor in the progression of chronic kidney diseases]. AB - As many as 34 patients with nephrotic syndrome (NS) and 42 patients suffering from type I diabetes mellitus without clinical manifestations of renal damage were examined for clinical and morphological signs of hyperperfusion renal damage (hyperfiltration, microalbuminuria, specific morphological alterations). The lack of renal functional reserves was regarded as a criterion for the status of hyperfiltration (oral protein administration, intravenous injection of small doses of dopamine). The risk of the progression of renal failure by the hemodynamic type in NS amounted to 65%. In the mechanism of the development of hyperfiltration in NS, the role of systemic hypertension, renal failure, a reduction of the ultrafiltration coefficient is discussed. Hypooncia does not make any material contribution to the development of hyperfiltration in NS. The clinical and morphological signs of hyperfusion renal injury were revealed in 50% of patients suffering from type I diabetes mellitus without the clinical signs of renal injury. PMID- 1440324 TI - [The basic groups of modern preparations. II. Loop diuretics. Osmotic diuretics. Aquaretics. Uricosuric diuretics]. PMID- 1440325 TI - [Problems in kidney physiology]. PMID- 1440326 TI - [The determination of apolipoproteins. Its possible diagnostic importance]. PMID- 1440327 TI - [The clinical use of norfloxacin (Nolicin) and ciprofloxacin (Ciprinol)]. PMID- 1440328 TI - [Lipiduria in the nephrotic syndrome]. AB - A study was made of urine lipids and their fractions in chronic glomerulonephritis (CGN) and renal amyloidosis with nephrotic syndrome (NS). 91 patients suffering from NS were examined. 2 subgroups were distinguished among these patients: with CGN of the nephrotic type and with the nephrotic stage of renal amyloidosis. The reference groups were made up of patients with latent CGN and healthy subjects. Measurements were made in the blood and urine of total lipids (TL) and their fractions--phospholipids (LP), free cholesterol (FC), mono- and diglycerides, triglycerides (TG), and cholesterol esters (CE). The presence of the NS was attended by a rise in the blood of TL concentration, relative content of FC, TG and by a decline of RL and CE, with the decrease of the relative content being more manifest in amyloidosis. Nephrotic lipiduria was largely characterized by an increase of the concentration of TL and of the relative content of PL, with the changes of the latter parameter being mostly characteristic of CGN patients. Thus, NS was associated with a high excretion of lipids with urine which is likely to reflect their elevated filtration under nephrotic hyperlipidemia. Still, in nephropathies whose pathogenesis is determined by an important role of inflammatory and membrane-destructive processes, of definite role is also the local (renal) formation of PL. PMID- 1440329 TI - [The effect of a protein loading test on the fibrinolytic system in patients with chronic glomerulonephritis and amyloidosis]. AB - Investigation of the reserves of the fibrinolytic system with the aid of protein stimulation was carried out in 10 patients with chronic glomerulonephritis and in 10 patients suffering from amyloidosis. All the patients manifested proteinuria exceeding 3.5 g/day and other symptoms of nephrotic syndrome of varying intensity. Renal function was preserved in all the patients. The reserves of the fibrinolytic system were measured by analyzing blood plasma and urine before and after beef protein stimulation. The data revealed reciprocal responses of activator activity in blood plasma and urine in patients suffering from chronic glomerulonephritis and amyloidosis. In patients with amyloidosis, the test revealed complete depletion of activator activity in urine while its considerable reserves were preserved in blood plasma of the systemic channel. PMID- 1440330 TI - [Immunoglobulin filtration and reabsorption as possible factors in the pathogenesis of chronic glomerulonephritis. Clinical, immunomorphological and histoenzymological research]. AB - Kidney biopsy specimens obtained from a group of individuals with chronic glomerulonephritis (CGN) have been processed for light and electron microscopic immunolocalization of total immunoglobulins (Igs). In a few cases, acid phosphatase (ACPase), a lysosomal enzyme marker, was ultrastructurally visualized. In the glomeruli, horseradish peroxidase-stained Igs were revealed in capillary lumina, urinary spaces and in transit through occasional loci of the glomerular basal membranes while ACPase-containing lysosomes resided both within and outside the cells. In the proximal tubules, Igs were traced in the endocytic vesicles and vacuoles, the latter also being positive for ACPase. Statistically significant relationships have been revealed between the number of IGs-labeled proximal tubules and some clinical or pathomorphological stigmata of CGN, in particular, proteinuria and arterial hypertension levels, marked interstitial sclerosis, etc. The data obtained are discussed in regard to the mechanisms of increased macromolecular filtration and the different proteinuria selectivity levels as well as the development of interstitial sclerosis as a result of the elevated reabsorption and incomplete lysosomal degradation of Igs in CGN. PMID- 1440331 TI - [The morphofunctional parallels in arterial hypertension in patients with chronic glomerulonephritis]. AB - The restructure of renal tissue in intravital nephric biopsy specimens, renin angiotensin-aldosterone together with kallikrein synthetic functions were studied and compared in patients with mesangioproliferative and membranoproliferative glomerulonephritis (MsPGN and MPGN). The characteristics of the morphological changes were defined. In MsPGN with secondary hypertension (SH), nephronic wasting and hyalinosis of arteries were mostly detectable whereas MPGN with SH was primarily marked by the derangement of the tubulointerstitial structures. In MPGN, the levels of total and inactive renin (TR and IR) were significantly higher than in MsPGN. This can be regarded as risk factor of early development of SH. The content of TR and IR and in addition that of active renin (AR) in MRGN did not depend on the clinical form of chronic glomerulonephritis. As compared to MsPGN with an isolated urinary syndrome, in MsPGN with SH, AR was prevalent, while its level correlated well with systolic and the mean arterial pressure. AR may be implicated in the mechanism of SH in MsPGN. In MPGN with SH, kallikreinuria was found to be extremely low, which may be consequent to tubulointerstitial injuries. The discoordination of the renin-angiotensin and kallikrein system may be one of the causes of earlier formation and the grave course of SH in the morphological pattern under consideration. PMID- 1440332 TI - [Probably the most burdensome event for the physician is the occurrence of severe, sometimes fatal, pathology as a result of performing one or another medical interventions]. PMID- 1440333 TI - [Acute kidney failure in patients with chronic glomerulonephritis]. AB - The causes of acute renal failure (ARF) and results of its treatment are analyzed in 34 patients aged 15 to 51 years with exacerbation of chronic glomerulonephritis (CGN). Of these, 20 patients presented with lupoid GN, 11 with Bright's GN, and 3 had GN associated with systemic vasculitis (2 of them also had mixed cryoglobulinemia). All the patients underwent clinical treatment that lasted from January 1, 1986 to December 31, 1990. In 15 patients, ARF was due to the activity of the underlying disease or development of its complications (nephrotic crisis, disseminated intravascular coagulation, cryoglobulinemia); in 15 patients, it was determined by complications induced by drug treatment (diuretics, antibiotics, nonsteroid antiinflammatory drugs), and in 4 patients, by complications related to invasive examinations (radiographic contrast studies) and treatment (isolated ultrafiltration). The authors hold that superaddition of progressive tubular disorders, rapid decrease of the rate of glomerular filtration accompanied by the growth of serum creatinine form the basis for ARF to be diagnosed in such patients. Identification of the cause of ARF and delimitation of whether the pathological process is renal or prerenal in CGN patients is required for rational treatment prescription. PMID- 1440334 TI - [The effect of pathogenetic therapy on the expression of endogenous intoxication in patients with chronic glomerulonephritis]. AB - The content of medium-sized molecules (MSM) in the blood serum was measured in 52 patients with exacerbation of chronic glomerulonephritis (CGN) given pathogenetic therapy. All the patients manifested an initial rise of the content of MSM. Administration of cytostatics and (or) glucocorticoids led to the regression of the nephrotic syndrome in 32 patients. In 20 patients, it was ineffective. All the patients in whom the treatment appeared effective demonstrated the lowering of the content of MSM 2 weeks after the treatment initiation, which outstripped the dynamics of the other parameters characteristic of CGN exacerbation. At the same time the urinary clearance of MSM remained unchanged. The patients in whom the pathogenetic therapy turned out ineffective manifested an increase of the blood content of MSM and of the urinary clearance of these substances. It is suggested that the test with the detection of the urinary clearance and the content of MSM in the blood serum may be used before the treatment and 2 weeks after its initiation to early estimate the treatment efficacy. The prognostic value of the positive test is 82%, that of the negative 80%. It is assumed that the mechanism that triggers the increase of the rate of MSM generation may lie in lipid peroxidation activation. PMID- 1440335 TI - [The correlation of different forms of primary glomerulonephritis today and their diagnostic criteria (the work experience of a nephrology department and a clinico morphological analysis of 3000 cases)]. AB - The author reviews the structure of nephropathies on the basis of an analysis of the clinicomorphological data obtained during the follow-up of 3000 patients examined at the nephrological center. In a group of primary glomerulonephritis, the mesangioproliferative form occurred most frequently (68%), the membranoproliferative form was encountered in 27.2% of cases, and the membranous form in 1.8%. Over the recent years not a single case of acute glomerulonephritis has been observed. Analysis of the diagnostic criteria allowed the antibody variety only to be regarded as an independent pattern of rapid-progressing glomerulonephritis. Equally to the manifestations of glomerulonephritis proper, mesangial proliferation should be also viewed as a possible nonspecific response to the other pathological processes. Focal glomerulosclerosis as a disease entity is to be excluded from the nomenclature of glomerulonephritis. PMID- 1440336 TI - [The characteristics of kidney involvement in chronic diffuse liver diseases due to the hepatitis B virus]. PMID- 1440337 TI - [Liver cirrhosis and lymphoproliferative diseases]. AB - Seven patients suffering from liver cirrhosis combined with lymphoproliferative diseases: chronic lymphoid leukemia (n = 4), lymphosarcoma (n = 3) were placed under observation. Viral etiology of liver cirrhosis was established in 4 patients (HBV markers were revealed in the serum in 2 and in liver tissue in 1) and was assumed in 3 patients (the lack in the anamnesis of other hepatotropic factors; multilobular form of liver cirrhosis). In 5 patients, the lymphoproliferative disease was diagnosed 2-30 years after the appearance of the symptoms of chronic diffuse liver disease. In 2 patients liver cirrhosis and hemoblastosis showed up simultaneously. The role of hepatitis viruses, HBV in particular, in the onset of lymphoproliferative diseases is under discussion. PMID- 1440338 TI - [The key problems of glomerulonephritis]. PMID- 1440339 TI - [Streptococcal infection and chronic glomerulonephritis in children]. AB - Microbiological, immunological and immunohistochemical studies were carried out in 78 children with different clinicomorphological forms of chronic glomerulonephritis (GN). According to the data obtained, the role of streptococcal infection (SI) is inconclusive in certain clinicomorphological forms of chronic GN, suggesting different approaches to the treatment of these patients. The etiological role of SI is most probable in mesangioproliferative and mesangiocapillary GN, manifesting by hematuric and mixed forms of chronic GN. Antibacterial therapy is indicated to patients with a rise of the level of ASL-O and with the clinical signs of acute SI or exacerbation of chronic tonsillitis in the same patients, especially during immunosuppressive therapy. PMID- 1440340 TI - [Antistreptococcal antibodies in the blood serum of glomerulonephritis patients]. AB - To study humoral antistreptococcal immunity, 29 patients with acute glomerulonephritis (AGN), 211 patients with chronic glomerulonephritis (CGN) and 30 healthy donors were examined. According to EIA, blood sera of the indicated groups demonstrated antibodies (AB) to structural components of Streptococcus--A polysaccharide (A-ps) and hyaluronic acid (HA) and to its extracellular products- streptokinase (SK) and streptolysin-O (ASLO). It has been shown that in the blood of AGN patients, the levels of AB to A-ps, SK and ASLO were high. The highest level of AB and SK was detected in 55% of the patients with the disease standing of up to half a year. In patients of all the clinical groups of CGN, the levels of AB to A-ps, SK and HA were elevated. The degree of the rise of the levels of all AB depended on the disease activity. Of prognostic importance in the chronicity of AGN and progression of CGN are high titers of AB and SK. The etiological role of streptococcus in glomerulonephritis and its importance in CGN exacerbation and prognosis are under discussion. PMID- 1440341 TI - [Immunosuppressive therapy with the use of cyclosporin A in the late period after a kidney transplant]. AB - A study was made of the results of kidney transplantation in 90 patients who received three-component immunosuppressive therapy (cyclosporin, azathioprine and prednisolone) in the induction phase, followed by cyclosporin conversion in the phase of maintenance therapy. The second patients' group (39 cases) received permanent three-component immunosuppressive therapy. Analysis of the data obtained makes it possible to regard the use of cyclosporin advisable not only in the induction, but also in the maintenance phases of immunosuppressive therapy. PMID- 1440342 TI - [The role of disorders in the structural-functional properties of the erythrocyte membranes and energy metabolism in the progression of anemia in patients with terminal kidney failure]. AB - As many as 30 healthy persons and 65 patients suffering from chronic glomerulonephritis with terminal renal failure (TRF) placed on program dialysis were examined for lipid composition of the membranes and functional properties of red blood cells. By the gravity of anemia the patients were distributed into 2 groups. It has been established that in the red blood cell membranes, there was an increase of the content of cholesterol and sphingomyelin, and a decline of the content of phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine. In addition to the changes in the lipid content of red blood cells, the peripheral red blood cell pool showed an increase of the amount of pathologically shaped cells, a reduction of the cell capacity to deformation, a rise of the content of fibrinogen in the supramembranous layer. Destruction of the phospholipid matrix of the red blood cell membrane was attended by noticeable restructure of the work of the multienzymic complex of glycolysis, resulting in energy metabolism destabilization. Analysis of the data obtained has demonstrated that as the structural and functional properties of the membranes underwent alterations and the mechanisms of stabilization of red blood cell energy homeostasis got disintegrated, anemia in patients with TRF became graver. PMID- 1440343 TI - [Lipid peroxidation as a possible mechanism of erythrocyte damage in patients with chronic kidney failure on hemodialysis]. AB - Ten patients with chronic renal failure (CRF) treated by hemodialysis (HD) were examined. All the patients demonstrated remarkable anemia. The red blood cell count was (2.7 +/- 0.2) x 10(12)/I the concentration of hemoglobin 79.5 +/- 5.6 g/l, on the average, hematocrit 23.2 +/- 1.8%. The content of malonic dialdehyde in the patients' red blood cells was far greater than in controls, amounting to 132% (per 1 ml of hemolysate), 134% (per 1 mg of protein) (p < 0.05). Catalase and glutathione peroxidase activity in the patients' red blood cells did not differ from that in controls. Superoxide dismutase activity reduced by 43% as compared to that in donors (p < 0.001). The authors review possible mechanisms of lipid peroxidation (LPO) and a decrease of antioxidant defense in red blood cells of CRF patients on hemodialysis. It is concluded that activation of LPO processes and the decrease of antioxidant defense produce a noticeable destructive effect on the integrity of the red blood cell membrane. They also influence the development of hemolysis. PMID- 1440344 TI - [The lipid peroxidation process in patients with nephrogenic hypertension and clinico-laboratory signs of chronic kidney failure]. PMID- 1440345 TI - [Disordered intestinal mechanisms in patients with chronic kidney failure]. AB - The data on impairment of the intestinal mechanisms in 103 patients with chronic renal failure are presented. This impairment is characterized by inhibition of the absorption capacity of the intestine, an increase of the concentration of urea and creatinine in its contents, and by dysbacteriosis. PMID- 1440346 TI - [The active rosette-formation reaction in assessing the immunomodulating activity of basic preparations in patients with rheumatoid arthritis]. PMID- 1440347 TI - [The modern concepts of hereditary nephritis]. AB - The authors describe the results of modern studies into the problems of genetics, clinical picture, prognosis and prospects of the treatment of inherited nephritis. It is assumed that at the basis of inherited nephritis there lies generalized impairment of the basal membranes, which is determined by mutation of X chromosome that codes the structure of the chains of the fourth fraction of collagen. The phenotypic heterogeneity of the disease is accounted for by mutation of different alleles in a solitary locus. The clinical characteristics of inherited nephritis without hypoacusis and Alport's syndrome in inbred and outbred families is provided as are specific features of the disease evolution. The results and efficacy of kidney transplantation in patients with inherited nephritis in the phase of chronic renal failure are discussed. PMID- 1440348 TI - [The basic mechanisms of the development of kidney failure and the methods for its correction in multiple myeloma]. AB - To examine functional capacities of the kidneys, reserve potentialities of the urinary tract and the mechanism of the development of chronic renal failure (CRF) in multiple myeloma (MM), 60 patients were examined. In addition to the routine methods of examination, all the patients were subjected to renal sonography. It has been shown that the main causes of CRF in MM are proteinemia and paraproteinuria. Emphasis is laid on the importance of sonography that enables one to measure not only the size of the kidneys, to estimate the status of the parenchyma and calyceal system, but also to reveal the derangement of urodynamics of the upper urinary tract in the stage of latent CRF. It has been demonstrated that one of the effective methods of removing CRF lies in therapeutic plasmapheresis, which is advisable in MM patients even in latent renal failure, preventing the impairment of the tubular system and increasing the filtration and reabsorption capacity of the kidneys. PMID- 1440349 TI - [The recovery of erythropoiesis after the short-term Recormon treatment of renal anemia]. PMID- 1440350 TI - [An unusual course of amyloidosis in rheumatoid arthritis patients]. PMID- 1440351 TI - [An epileptic syndrome in systemic lupus erythematosus]. PMID- 1440352 TI - [Hemostasis and the kidneys (I)]. PMID- 1440353 TI - [The correlation of the lipoprotein (a) level of the blood serum with the degree of coronary atherosclerosis]. PMID- 1440354 TI - [The prediction of the late effect of charcoal hemoperfusion in rheumatoid arthritis patients]. AB - Hemocarboperfusion is effectively used for the treatment of serious cases of rheumatoid arthritis (RA). The effectiveness of the treatment may be decreased by possible development of the rebound syndrome (RS) after the treatment. The useful retrospective frequency analysis does not often allow predicting the development of RS. The authors devised the system of forecasting the development of RS depending on the body state by means of an analysis of the results in the group of 38 patients with classical RA treated by hemocarboperfusion. They also designed a statistical model with the help of linear regression and correlation methods. It allows counting the degree of the predisposition to RS development for each patient both numerically and individually. The precision of the conclusion based on the method is about 90%. The results of the forecasting give the general characteristics of RA development and can be used as an additional argument for prescription of hemocarboperfusion. PMID- 1440355 TI - [The prevalence of and risk factors for osteoarthrosis in workers in tire manufacture]. AB - The data of epidemiological studies of rheumatic diseases, carried out at the Yaroslavl tire factory among 2508 workers are provided. Overall 845 subjects afflicted with different rheumatic diseases were identified. The prevalence of osteoarthrosis of the peripheral joints was 12.68 +/- 0.66%. The main industrial risk factors of osteoarthrosis were distinguished: occupational hazard (physical overloads), work record in the main specialty over 5 years, functional and static dynamic loads of the bones and joints, elevated temperature and air humidity in industrial premises. As to the other factors, age, defects of the skeleton, hereditary load, foci of chronic infection, primary education, female sex, and the character of feeding turned out significant for the development of osteoarthrosis. The authors have worked out the tables of risk for osteoarthrosis of the peripheral joints, the use of which allows predicting the morbidity of every worker and distinguishing risk groups with a purpose of carrying out early treatment and prophylactic measures. PMID- 1440356 TI - [The intensive therapy of multiple organ failure in myelotoxic agranulocytosis in a patient with acute leukemia]. PMID- 1440358 TI - [The treatment of erythremia]. PMID- 1440357 TI - [A combination of myelomatous disease with generalized xanthomatosis]. PMID- 1440359 TI - [The first Russian trial of treating patients with acute nonlymphoblastic leukemias with novantrone combined with cytosar]. PMID- 1440360 TI - ["Small doses" of cytosar in the therapy of acute nonlymphoblastic leukemias]. PMID- 1440361 TI - [The significance of the erythrocyte antioxidant system in the development of anemia in hemoblastosis patients]. PMID- 1440362 TI - [Chromosome aberrations in the inhabitants of Gomel and Gomel Province: the results of living in radioactively contaminated areas]. PMID- 1440363 TI - [Modern oncological hematology--medicine of critical decisions]. PMID- 1440364 TI - [An expanded radical program of radiation therapy with prophylactic irradiation of the lungs in lymphogranulomatosis]. PMID- 1440365 TI - [The strategy for the therapy of acute myeloid leukemias in adults]. PMID- 1440366 TI - [The use of novantrone in combination with other preparations in hematosarcoma patients]. PMID- 1440367 TI - [The clinical significance of the immunophenotyping of the tumor cells in nonleukemic hemoblastoses of a lymphatic nature]. PMID- 1440368 TI - [A trial of using farmorubicin in the therapy of malignant lymphomas]. PMID- 1440369 TI - [The determination of the beta 2-microglobulin level in malignant lymphomas]. PMID- 1440370 TI - [The chemoradiation treatment of patients with aggressive non-Hodgkin's lymphomas in the III-IV stages of the disease]. PMID- 1440371 TI - [Methods of treating spinal cord involvement in multiple myeloma]. PMID- 1440372 TI - [Circulatory failure and the methods for its correction in multiple myeloma]. PMID- 1440373 TI - [The clinical manifestations and course of blood system diseases in elderly and old disabled veterans of World War II]. PMID- 1440374 TI - [Alternative approaches to the treatment of aplastic anemia patients]. PMID- 1440375 TI - [The use of cyclosporin A in treating partial red-cell aplasia of the bone marrow and aplastic anemia]. PMID- 1440376 TI - [Congenital hemolytic anemia caused by the carriage of hemoglobin Bristol beta 67 Bal-->Asp]. PMID- 1440377 TI - [The effect of correcting anemia with recombinant erythropoietin on the central hemodynamic indices of patients on regular hemodialysis]. PMID- 1440378 TI - [The role of the radionuclide study method in the diagnosis and therapy of hemophilic joint lesions]. PMID- 1440379 TI - [Selective lymphapheresis (a method for the selective elimination of cellular elements and fibronectin complexes from the lymph) in systemic scleroderma]. PMID- 1440380 TI - [The generation of active forms of oxygen by the leukocytes and their role in the development of chronic gastroduodenal diseases]. PMID- 1440381 TI - [The rational use of De-Nol in the treatment of peptic ulcer and chronic active gastroduodenitis associated with Helicobacter pylori]. PMID- 1440382 TI - [Dilated cardiomyopathy--the diagnostic and treatment possibilities under outpatient polyclinic conditions]. PMID- 1440383 TI - [Modern diuretic preparations. III. Potassium-saving diuretics]. PMID- 1440384 TI - [The clinical heterogeneity of the scleroderma group of diseases]. PMID- 1440385 TI - [Verapamil--on the 30th anniversary of its clinical use]. PMID- 1440386 TI - [The pathogenetic therapy of lupus glomerulonephritis]. PMID- 1440387 TI - [The use of enterosorbent SKN in hyperlipoproteinemias (clinical and experimental research)]. PMID- 1440389 TI - [A comparative assessment of 2 approaches to the electrical impulse treatment of atrial fibrillation. 1. The immediate results and complications]. PMID- 1440388 TI - [Dynamic changes in the histamine and serotonin levels of acute myocardial infarct patients treated with strepodecase, finoptin and alpha-tocopherol acetate]. PMID- 1440390 TI - [The development of pharmacology and the appearance every year of newer and newer drugs has significantly complicated the work of the physician (editor)]. PMID- 1440391 TI - [The chronotropic and hemodynamic effects of finoptin in patients with a permanent form of atrial fibrillation]. PMID- 1440392 TI - [Estulic (guanfacine) in the treatment of arterial hypertension]. PMID- 1440393 TI - [The effect of long-term therapy with a calcium antagonist on thrombocyte function in hypertension patients]. PMID- 1440394 TI - [The current status of the science of antibiotics and the outlook for its development]. PMID- 1440395 TI - [Changes in the central hemodynamics and kidney activity during the enalapril treatment of hypertension patients]. PMID- 1440396 TI - [The efficacy of combined therapy with immunodepressants, anticoagulants and antiaggregants in certain clinico-morphological variants of chronic glomerulonephritis]. PMID- 1440397 TI - [The role of hippurate in kidney failure]. PMID- 1440399 TI - [Experience with the use of endovascular blood irradiation with helium-neon laser light in patients with chronic glomerulonephritis and disordered kidney function]. PMID- 1440398 TI - [10-years' experience in using enterosorption for treating chronic kidney failure]. PMID- 1440400 TI - [A multicenter trial of Recormon within the framework of international controlled research]. PMID- 1440401 TI - [The prognosis of lupus nephritis during treatment with superhigh-dose cyclophosphane]. PMID- 1440402 TI - [The efficacy of Capoten in treating rheumatoid arthritis with arterial hypertension: an analysis of its hypotensive and anti-inflammatory actions]. PMID- 1440403 TI - [The extracorporeal immunopharmacotherapy of severe glucocorticoid-dependent atopic diseases]. PMID- 1440404 TI - [The treatment of patients with duodenal peptic ulcer with a synthetic prostaglandin E2 analog (enprostil)]. PMID- 1440405 TI - [The programmed therapy of acute lymphoblastic leukemia in adults]. PMID- 1440406 TI - [The therapeutic results in acute myeloid leukemias in elderly patients]. PMID- 1440407 TI - [The procedure for antianginal therapy with Isoket and nitrosorbide]. PMID- 1440408 TI - [A comparison of the efficacy of clindamycin and penicillin in anaerobic lung infections]. PMID- 1440409 TI - [The optimal times, season and indications for the sanatorium treatment at Bairam Ali of patients with different forms of glomerulonephritis]. PMID- 1440410 TI - [Hematuria as a manifestation of drug disease]. PMID- 1440411 TI - [Diagnostic difficulties and therapeutic success in Wilson-Konovalov disease]. PMID- 1440412 TI - A comparison of gingival marginal gap formation in composite inlays using three different fabrication techniques. AB - The purpose of this study was to evaluate the accuracy of composite inlays fabricated with three different techniques. Using 2-factor ANOVA it was found that after light curing, the Direct Method was the most accurate. After readapting and heat curing, the Indirect Method was not different from the Direct Method. The same was true after 24 hours' storage in water. The direct method is recommended if proximal contours and contact can be adequately controlled. If an Indirect Method is used, it is recommended that the laboratory use an additional cured layer of composite material in the gingival margin after initial curing to minimize the gaps. PMID- 1440413 TI - Alternative methods of ventilation during CPR training of the dental team using a bag-mask technique. PMID- 1440414 TI - Selective developmental toxicity: misuse of the concept via mis-application of a mis-defined "A/D ratio". PMID- 1440415 TI - Ellagic acid protects rat embryos in culture from the embryotoxic effects of N methyl-N-nitrosourea. AB - Ellagic acid is a naturally occurring plant phenol that has demonstrated anticarcinogenic and antimutagenic activity in several test systems. Given the common proposed etiopathogenic processes of mutagenesis, carcinogenesis, and teratogenesis induced by genotoxic chemicals, the present study was initiated to determine whether ellagic acid would protect rat embryos in culture from the teratogenic effects of N-methyl-N-nitrosourea (MNU). Ellagic acid alone (as used in these experiments; 50 microM in DMSO) was not embryotoxic. Ellagic acid (50 microM) significantly (P less than 0.01) prevented MNU (75 microM)-induced effects including mortality (absence of heart beat), abnormal formation of the cephalic neural tube derivatives, and delayed differentiation as assessed by a morphological scoring system. These embryoprotective effects were dose responsive. Sequential treatment of embryos with ellagic acid followed by MNU in fresh media also was embryoprotective with no diminution of effect. The site at which ellagic acid interrupts the critical teratogenic events induced by MNU is apparently within the embryo and/or placenta. This model of chemical embryoprotection may be useful in determining the role of cell death and/or mutation in the teratogenic mechanism of action of methylating agents. PMID- 1440416 TI - Spina bifida aperta induced by valproic acid and by all-trans-retinoic acid in the mouse: distinct differences in morphology and periods of sensitivity. AB - The antiepileptic drug valproic acid (VPA) has been implicated as a human teratogen causing spina bifida aperta. Recently, we developed a mouse model inducing spina bifida aperta with VPA. To elucidate the pathogenesis of VPA induced spina bifida aperta we now investigated the anatomy and histology of this defect in the mouse. The morphology of spina bifida aperta induced by all-trans retinoic acid (RA) was used for comparison. Various doses of VPA and RA were administered at different times to determine the periods of sensitivity for inducing spina bifida aperta with these drugs. Each administration regimen consisted of three doses applied at intervals of 6 hr. RA induced spina bifida aperta during an earlier developmental period (day 8 of gestation) than VPA (day 9 of gestation). The most effective regimens for induction of spina bifida aperta in mice were injections of 3 x 500 mg VPA-Na/kg body weight (b.w.) intraperitoneally on day 9 of gestation at 0, 6, and 12 hr; RA (12.5 mg/kg b.w.) was given orally on day 8 of gestation at 12 and 18 hr, day 9 at 0 hr. VPA did not induce spina bifida aperta on day 8 of gestation and RA did not induce this effect on day 9 of gestation. Histological studies of day 18 fetuses carrying spina bifida aperta were performed. The spina bifida aperta induced by VPA shows a disorganized and necrotic spinal cord. In the vertebral canal were observed cell debris, blood cells, capillaries, macrophages, and rests of meninges. These results indicate that the spinal cord is almost destroyed at the affected section. In contrast, the spina bifida aperta induced by RA demonstrates a spinal cord organized in the gray and white matter, the dorsal and ventral horn. But the neural canal does not exist, only a layer of ependymal cells lies on the surface of the spinal cord. Our results indicate that the morphology of spina bifida aperta induced by VPA differed distinctly from that induced by RA in the mouse fetus. Moreover VPA produced a spina bifida aperta with a specific morphology. Also the period of sensitivity for induction of this lesion differed and occurred earlier for RA than for VPA. VPA and RA may possibly induce spina bifida aperta via different mechanisms in the mouse. PMID- 1440417 TI - Embryotoxicity of T-2 toxin and secalonic acid in embryonic chicks varies with the site of administration. AB - A crucial role of the site of administration in the sensitivity of the alternative system using chick embryo for testing embryotoxicity was demonstrated by morphological evaluation of the effects of T-2 toxin and secalonic acid D, and by incorporation of [14C]sodium acetate radioactivity. Secalonic acid D, administered to 2-, 3-, and 4-day-old embryos in doses higher than 1 microgram produced mostly malformations of the face (bilateral cleft beak, microphthalmia) while the teratogenic effects of T-2 toxin were being limited to the embryonic trunk of 2-day-old embryos (rumplessness) after administering doses higher than 0.001 microgram. In case of subgerminal and intraamniotic injections, the doses of both mycotoxins needed for producing embryotoxic effects comparable to those obtained with the more commonly used yolk sac injections appeared to be lower by one and two orders of magnitude, respectively. The results stress the need of using the shortest transport channel of test substances from the site of application to the target tissues of the embryo, when the maximum sensitivity and reproducibility of the test system are to be expected. PMID- 1440418 TI - Inner ear malformations induced by isotretinoin in hamster fetuses. AB - Inner ear malformations induced in anotic hamster fetuses following maternal treatment with 50 mg/kg isotretinoin (13-cis-retinoic acid) on gestational day 8 are described. Computer-assisted three dimensional reconstruction was used. Two general types of defective vestibulocochlear development were seen. Defects were bilateral and correlated with extent of middle ear deficiency and severity of mandibular defects. In the more severely affected fetuses the inner ear was limited to an epithelial sac with occasional small projections, no apparent innervation and a correspondingly reduced otic capsule. In most of the fetuses examined the inner ear was less severely affected and was characterized by a reduction in the number of semicircular ducts and alterations in the size and shape of the cochlear duct. These defects are similar to those seen in a child with the isotretinoin embryopathy. Pathogenesis may result from a direct effect on otic epithelium or from faulty inductive interactions with the rhombencephalon or with periotic neural crest cells. PMID- 1440419 TI - Effects of a 48 hour continuous intravenous infusion of CGS 13080-primagrel, a selective thromboxane synthetase inhibitor, on the perinatal and early postnatal period in the guinea pig. AB - CGS 13080, imidazo[1,5-a]pyridine-5-hexanoic acid, was evaluated for perinatal and postnatal effects in third trimester pregnant guinea pigs and their offspring. The compound was administered via 48 hour continuous intravenous infusion to a group of pregnant guinea pigs (n = 16) at a dose of 3 mg/kg/hr starting on gestational day 52 (via chronically implanted indwelling jugular venous cannulas). A saline control group (n = 12) received equivalent volumes of normal saline 0.5 ml/kg/hr throughout the dosing period. A third group (surgery sham, n = 16) was subjected to cannulation but not infused. A gross examination of each dam and piglets was conducted at necropsy on day 5 of lactation. The neonatal brains and all gross lesions (maternal and neonatal) were removed and fixed for histopathological examination. Compound-related clinical signs were noted in dams during the dosing phase of gestation. Six guinea pigs developed cephalic lymphatic swelling during the infusion. This observation may be correlated to the reported redistribution of fluid volume to the thorax of guinea pigs given intravenous injections of CGS 13080. There were no compound-induced effects on labor, delivery, or any of the examined reproductive parameters. There were no compound-related clinical signs, or effects on survival, body weight and developmental parameters in the F1 generation. Histopathological examination of the brains and other organs did not reveal any compound-related abnormalities. Based on these results, it was concluded that CGS 13080 did not elicit adverse perinatal and postnatal effects in guinea pigs. PMID- 1440420 TI - Developmental stages of the CD (Sprague-Dawley) rat skeleton after maternal exposure to ethylene glycol. AB - Ethylene glycol (EG), a chemical which causes skeletal malformations in rats, was administered by gavage to sperm positive CD rats on gestational days (gd) 6 through 15 at doses of 0 or 2,500 mg/kg/day to assess its effects on the pre- and postnatal skeletal development. Dams and fetuses/pups were killed on gd 18, 20, postnatal day (pnd) 1, 4, 14, 21, or 63, and offspring were double-stained for examination of skeletal malformations and degree of ossification of rapidly developing skeletal districts. No difference in gestational day of delivery between controls and the EG-treated dams was seen. Fetal weights per litter were significantly decreased with EG treatment in both the gd 18 and 20 groups. Pup body weight on pnd 1 was significantly below controls; however, EG had no effect on pup body weight on pnd 4-63. The percentage of fetuses/pups with skeletal malformations per litter was significantly increased after EG exposure for all time points except at pnd 63, with a predominance of axial skeletal defects. The percentages of total ossification, of sternabrae ossified, and of vertebral centra ossified were significantly reduced in the EG groups on gd 20 and on pnd 1 21, but not on gd 18 or on pnd 63. When the ossification data were subjected to statistical analysis with fetal/pup weights as a covariate, the values for EG exposed pups on gd 20 were not statistically significantly different from the control values. The reduced ossification values for EG-exposed pups on pnd 1-21 retained statistical significance even after covariate analysis. There was no effect of dose or body weight on ossification of fore- or hindlimb digits. In conclusion, the differences in incidence of skeletal alterations observed prenatally and through pnd 21 were not evident by pnd 63, suggesting that perinatal skeletal abnormalities may not always be permanent. PMID- 1440421 TI - Comparison of staging systems for the gastrulation and early neurulation period in rodents: a proposed new system. AB - Because there is no standard developmental staging system for the early postimplantation period of rodent embryos, investigators must now choose between a variety of systems that differ significantly. We have reviewed many of these staging systems and have summarized the ambiguities within them and the inconsistencies among them. In order to compare systems, we first obtained a consensus of the order of developmental events from the literature, and then attempted to fit existing systems into this order taking into account inconsistencies in terminology and blurred borderlines between stages. We were able to do this for most systems but not all because some were too divergent. We found that inconsistencies in definition of some terms, such as "primitive streak stage" and those used to describe the early neurulation process (neural plate, neural groove, neural folds, and head fold) cause much confusion. In order to develop an unambiguous system which can be used by all investigators, we propose to modify Theiler's system, which is one of the most commonly used systems but is not defined precisely during the early postimplantation period. We suggest making subdivisions of the original stages as follows: 1) stage 8 into 8a and 8b, by the degree of extension of the proamniotic cavity into the extraembryonic region; 2) stage 10 into 10a and 10b, by the completion of amnion formation; 3) stage 11 into 11a, 11b, and 11c, by the appearance of neural folds and foregut pocket. After Stage 12, the number of somite pairs can be used to precisely stage embryos.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440422 TI - Genetic differences in heat-induced tolerance to cadmium in cultured mouse embryos are not correlated with changes in a 68-kD heat shock protein. AB - Heat-induced cross-tolerance to cadmium was investigated in two inbred strains of mice, BALB/c and SWV, using a whole embryo culture system. Embryos were exposed to a pretreatment of 5 min at 43 degrees C and subsequently to an embryotoxic concentration of cadmium, 1.75 microM. The two types of embryos responded differently to the heat pretreatment, as cross-tolerance was induced in SWV but not in BALB/c mice. In SWV embryos, prior exposure to 43 degrees C for 5 min essentially eliminated the negative effects of cadmium on embryonic development and growth. However, in BALB/c embryos, no protection was observed. The variation in development of cross-tolerance in embryos from the two strains of mice was not correlated with differences in the induction of a 68-kD heat-shock protein (hsp68). There was a rapid increase in this protein in both strains after the initial heat exposure but not excess induction in the SWV strain that developed tolerance. The induction of hsp68 is therefore not sufficient to elicit cross tolerance, and other mechanisms are likely to be important in the protective response of the embryo. PMID- 1440423 TI - UT anatomist critiques Leonardo's drawings in Houston exhibition. PMID- 1440424 TI - TMA president stresses importance of "sunset" process. PMID- 1440425 TI - Health commissioner stresses need for preventive care. PMID- 1440426 TI - Disaster! When catastrophe strikes. Physicians' roles in emergency planning. PMID- 1440427 TI - OSHA blood borne pathogens standards. PMID- 1440428 TI - Treatment of patients with asthma in the 1990s. AB - The treatment of patients with asthma in this decade requires an understanding of the inflammatory process in their airways. A combination of bronchodilators and inhaled medications that reduce or prevent this inflammatory process provides the best treatment for this population. Because the inhaled anti-inflammatory medications do not offer the immediate clinical response that bronchodilators will provide, patient education regarding proper management becomes more critical. The patient's assistance in frequently monitoring the function of the airway can help both the patient and the physician implement the necessary changes in medications to reduce the severity of or to prevent an asthma attack. Through these monitoring and treatment techniques, mortality and morbidity caused by asthma can be reduced. PMID- 1440429 TI - Management of the patient with an abnormal Papanicolaou smear. AB - Any patient with an abnormal Papanicolaou smear should undergo colposcopic evaluation. Histologic examination of tissue obtained by biopsy and by endocervical curettage is essential for a proper diagnosis. Conization of the cervix has very well-defined indications. PMID- 1440430 TI - Universal access: the other side of the argument. PMID- 1440431 TI - Let's watch the language when talking about managed care. PMID- 1440432 TI - [The history of bronchial asthma]. AB - 'Panta rhei': everything flows. The significance of bronchial asthma is currently changing to no less a degree than medicine itself. In order to know where we are, we must know where we have come from. The historical course of bronchial asthma to some extent reflects the history of medicine itself: the Hellenic systems were followed by Byzantine, Galenic teaching methods, while Humanism and the Renaissance were followed by the considerable fireworks of early modern medicine. This continued with Magendie's experimental revolution in the 19th century and, finally, analytic medical research up to today. PMID- 1440433 TI - [Asthma and sleep]. AB - In asthmatics, nocturnal cough and dyspnea are much more common than generally known. Therefore, patients with asthma must be asked specifically whether they suffer from symptoms of asthma at night. Usually, nocturnal wheezing is a sign of a badly controlled asthma. Nocturnal bronchoconstriction appears to be an exaggeration of the normal circadian changes in airway calibre. The cause of this exaggeration is not well understood, and it's origin is presumably multifactorial. Careful treatment of nocturnal asthma is particularly important because many deaths due to asthma occur at night and because regular disturbance of sleep impairs performance during the day. Inhaled corticosteroids and beta 2 agonists, especially the new long-acting beta agonists, are first-line drugs for therapy. PMID- 1440434 TI - [Neglected allergens]. AB - The atopic symptoms manifest themselves mainly in hay fever or bronchial asthma. In a not inconsiderable number of cases, the question of oral complaints, connected with the intake of certain foodstuffs, is ignored in the medical anamnesis. Here, we are dealing with what is known as food-associated allergy syndrome, which is largely based on a cross reaction between certain types of pollen (birch, alder, hazel and mugwort) and food allergens (drupes, pomes, nuts, vegetables such as celery, carrots and fennel, etc.). Whereas following the intake of fruit the complaints are usually restricted solely to the oral cavity and the throat (aphthas, stomatitis, swelling of the lips and/or tongue, irritation of the hard palate, hoarseness and compulsive clearing of the throat), nuts and celery among others from the family Compositae often cause acute, allergic attacks with sometimes serious general symptoms such as laryngeal oedema, bronchial asthma, urticaria and even anaphylactic shock. In the sensitization against animal allergens, it must not be forgotten that the most powerful immunogens are to be found, for example, in the urine of small rodents (mice and rats). In the manufacture or application of fish food with red gnat larvae, people who are disposed to this will often react with an attack of bronchial asthma. PMID- 1440435 TI - [Immunotherapy of asthma: pro and contra]. AB - Specific immunotherapy (IT) introduced in 1911 for the treatment of asthma is still controversial, since many protocols have been devised empirically, some extracts are still poorly defined, the mechanisms of action are not yet clear and allergen injections can cause serious side effects. However, clinical efficacy of allergen-specific IT in hay fever with seasonal asthma and in selected patients with perennial asthma has been convincingly documented. For optimal effectiveness IT should be restricted to appropriately selected patients with proven IgE mediated disease. IT has seldom the capacity to act as a curative treatment. However, a considerable reduction in symptoms and drug consumption is of sufficient benefit. The clinical efficacy of IT should not be solely compared to symptomatic therapy, since IT should be considered as a part of a multifactorial approach aimed at interfering broadly with the pathophysiology of allergic diseases. PMID- 1440436 TI - [Chronic cough]. AB - Cough is a powerful physiological reflex mechanism that causes central airways to be cleared of foreign material and excess secretions. Chronic cough is a very common presenting symptom in general practice with a prevalence in the population of about 5%. As a general rule, persistent cough represents organic disease of the upper and lower airways, the lung parenchyma, the pulmonary circulation, the pleural space, the mediastinum and the upper gastro-intestinal tract. The most common cause is cigarette smoking, but virtually any chronic lung disease may be occasionally associated with cough. Complications of coughing are tussive syncopes, rib fractures, rupture of respiratory muscles and eventually hernias. Based on a detailed clinical history and physical examination, the investigation includes a chest radiograph, spirometry, and sputum smears. Radiography of the sinuses, bronchoscopy and upper gastro-intestinal endoscopy may be added. If the treatment of an underlying disease is successful, chronic cough may disappear. There are few 'antitussive' drugs with proven suppression of the cough reflex. PMID- 1440437 TI - [Chronic bronchitis: when are antibiotics indicated?]. AB - The role of bacterial infections in chronic obstructive pulmonary diseases is still poorly understood, and so is the importance of antimicrobial chemotherapy. Based on the present knowledge from clinical studies, it is suggested that antibiotic treatment should be initiated for seven to ten days in patients suffering from an 'Anthonisen type-1 exacerbation', i.e. clinical deterioration with a significant increase in sputum production and sputum purulence, but not in others. The best tolerated, least toxic and least expensive oral antibiotic with adequate activity against pneumococci and H. influenzae is probably most appropriate. These prerequisites are still best fit by aminopenicillins and cotrimoxazol. PMID- 1440438 TI - [Chronic bronchitis: rare etiology]. AB - Chronic bronchitis is defined for epidemiologic and clinical purposes as the presence of productive cough for three months in each of two successive years. Based on symptoms, the term 'chronic bronchitis', therefore, does not describe one distinct disease. It is rather a collective name for the clinical manifestation of numerous different congenital or acquired chronic diseases of the trachea, the bronchi and the bronchioli. Cigarette smoking is the most consistently important (and preventable) determinant of chronic bronchitis. There are, however, other rare etiologic factors, including malformations, tumors, recurrent aspirations and bronchiectasis. The latter often occur in association with systemic disorders such as cystic fibrosis, immotile cilia syndrome, immunodeficiency, alpha 1-antitrypsin deficiency and others. PMID- 1440439 TI - [Chronic asthmatic bronchitis]. AB - Many patients with chronic obstructive pulmonary disease (COPD) episodically or continuously have asthmatic signs with a degree of reversibility in response to bronchodilators. In such cases, the diagnosis 'chronic asthmatic bronchitis' is often used, although the cause-effect relationship between COPD and asthmatic manifestations is not established. Hence, the 'chronic asthmatic bronchitis' is not a pathogenetic diagnosis, but rather a working diagnosis which implies a specific treatment of the reversible component of chronic airway obstruction. Certainly, the most important measure to avoid a rapid progression of COPD is the elimination of damaging agents by inhalation (smoking). In addition, it was a widely accepted belief that these patients require a continuous inhalation therapy with beta-agonists or anticholinergics. However, there is new evidence, indicating that a continuous treatment might accelerate the decline in ventilatory function and that a better long-term outcome might be achieved by on demand inhalations. PMID- 1440440 TI - [Case of the month: cough, dyspnea and joint pain]. PMID- 1440441 TI - [Wound management]. AB - The following article is a check-list for wound care giving some practical hints. Special interest has been given to the themes of local anesthesia and prevention of infections. The indications and limits of the ambulant wound care are also discussed. Finally, a short explanation is given for the treatment of wounds situated at delicate regions of the body. PMID- 1440442 TI - [Ambulatory plastic surgery]. PMID- 1440443 TI - [Ambulatory hand surgery]. AB - The majority of surgical interventions about the hand can be done on an outpatient basis and in private practice; however, the surgeon must be well trained in hand surgery and should master all forms of local and regional anesthesia, permitting an atraumatic technique. In addition, he must be prepared to handle any peri- and intraoperative complication and should be able to refer the patient to a close-by hospital in case of need. Since the aftercare appears to be of paramount importance for a successful outcome, the postoperative rehabilitation must be guaranteed as well. As all these conditions require qualified manpower and a good infrastructure, hand surgery is probably best performed within a small group of practising surgeons. PMID- 1440444 TI - [Lunate dislocation]. PMID- 1440445 TI - [Status of the family physician in ambulatory surgery]. AB - Due to progress in anesthesia and new operating techniques, ambulatory surgery is advancing. The family doctor attends to the preoperative examination, the immediate postoperative care, the subsequent treatment and rehabilitation. To grant interdisciplinary collaboration, the hospital must establish exact instructions for preliminary examination and after-treatment as well as organize regular postgraduate meetings, thus intensifying relations between the family doctor and the surgeon. PMID- 1440446 TI - [Ambulatory phlebectomy]. AB - Ambulatory phlebectomy has been done already in Greek and Roman times. It was since forgotten for many centuries, but it has been revived by Muller in 1956. Ambulatory phlebectomy is one of the most rewarding instances of ambulatory surgery. It consists of the comprehensive extraction of the varices through extremely small stab incisions, followed immediately by vigorous marching. It calls for team work: The surgeon performs the high ligation and stripping of the proximal third of the greater saphenous vein, and the phlebologist removes all the other varices. And it is an almost ideal treatment, as it provides efficiency as well as excellent cosmetic results at low costs and is also harmless. PMID- 1440447 TI - [Ambulatory treatment of varicose veins]. AB - Only a small part of the varicose veins need inpatient treatment. Restricting strippings to the diseased saphenous segments and the use of Muller's technique ('phlebectomie ambulatoire') permits the majority of patients to be treated on an ambulatory basis. In 1990 and 1991, 453 of 723 operations were performed under local anesthesia. 233 of the 686 insufficient long and short saphenous veins were treated by high ligation-with or without stripping-in local anesthesia. The limitations of ambulatory surgery are defined by the extension of the varices and by the presence of a seriously diseased long saphenous vein necessitating a stripping. PMID- 1440448 TI - [Surgical indications for partial inpatient and ambulatory surgery of the lower extremities]. AB - Outpatient (ambulatory) surgery has become widely accepted in free-standing outpatient surgery centres and in hospitals covering the field of hand surgery as well as, increasingly, the field of lower-extremity surgery. Three factors are decisive for secure ambulatory surgery: adequate material and personal resources guaranteeing a round-the-clock medical service, outpatient anesthesia which focuses mainly on the perioperative care of outpatient surgery, and a well informed patient. Under these prerogatives the majority of surgical procedures of the lower extremities are performed on an outpatient basis without any undue risk. This includes also the diagnostic and operative arthroscopy of different joints. PMID- 1440449 TI - [Ambulatory surgery at the surgical clinic and polyclinic of the Munich Technical University]. AB - Day-care and especially short-stay surgery were found attractive logistics for surgery of the hand, inguinal hernia repair, laparoscopic cholecystectomy, invasive measures for tumor staging such as diagnostic laparoscopy and implantation of vascular ports for chemotherapy. This new way of surgical organization is a practical alternative to overcome increasing limitations of hospitalization capacities and to conserve everyday surgery which is necessary for the teaching of students and surgical beginners within otherwise highly specialized institutions. PMID- 1440450 TI - [Ambulatory ophthalmologic surgery]. AB - In the past years, more procedures (including intraocular surgery) have been performed on an outpatient basis, thanks to the added safety of microsurgery. The decision of whether to operate on an outpatient basis should not just be based on the kind of procedure but more on the patient's suitability and on his social context. The patient must be able to come daily to the office, and eye medication must be applied as prescribed by a relative or a neighbour. PMID- 1440451 TI - [Ambulatory pediatric surgery]. AB - The authors refer about their experience in ambulatory pediatric surgery performed in pediatric clinics or in their own practice. Indications are listed, conditions, advantages and disadvantages are discussed. 562 operations were completed from February 1991 to January 1992, 181 (32%) under practice conditions with an experienced anesthesiologist. No complications had to be reported, and no patient was hospitalized due to surgical or anesthetic complications. But indications for ambulatory surgery have to be strictly noted, and only children in excellent health should be anesthesized. The decision about operability has to be made by the anesthesiologist in charge. PMID- 1440452 TI - [Ambulatory hernia surgery]. AB - Ambulatory surgery for hernia repair is not generally used in Switzerland. Tradition, patients' expectations and the insurance system still favour hospitalization. Nationwide, the mean length of stay amounted to 8.7 days in 1990. A five-year experience is presented, using transversalis fascia repair for uncomplicated unilateral hernia and encouraging immediate ambulation. In 530 patients, the mean duration of hospital stay was 4.4 days. In 446 of these cases, local anesthesia was used, and two thirds of the patients were discharged by the second postoperative day. Thus, it seems possible to gradually approach short stay surgery for inguinal hernia repair even in Switzerland. PMID- 1440453 TI - [Ambulatory laparoscopic cholecystectomy?]. AB - Commonly, after laparoscopic cholecystectomy, patients will be discharged from the hospital on the second or the third postoperative day and return to full activities about a week after surgery. Some reports from the USA demonstrate that laparoscopic cholecystectomy can be done on an outpatient basis. But these as well as all operative procedures are not without risk, and we prefer a short hospitalization. Outpatient laparoscopic cholecystectomy is performed because cost containment has become a major issue in American medicine. PMID- 1440454 TI - [Ambulatory surgery--urology]. AB - Similar to other surgical specialties, there are in urology a considerable number of interventions that may be performed on an outpatient basis. This holds true also for the rapidly evolving endoscopic urology. Well-established and new indications are discussed and modern operative techniques described. However, the move to more outpatient or day surgery with fewer and shorter hospital stays will, in Switzerland, mostly depend on the health care financing system or on 'who pays for what'. PMID- 1440455 TI - [Ambulatory proctologic surgery]. AB - An increasing number of proctological procedures may be performed on outpatients under extensive local anesthesia or by posterior perineal bloc. Precise selection criteria should be observed. Results of 1233 outpatients procedures are reported. PMID- 1440456 TI - General practitioners and asthma. PMID- 1440457 TI - Lung sounds. PMID- 1440458 TI - The cost of care in cystic fibrosis. PMID- 1440459 TI - Lung sound intensity in patients with emphysema and in normal subjects at standardised airflows. AB - BACKGROUND: A common auscultatory finding in pulmonary emphysema is a reduction of lung sounds. This might be due to a reduction in the generation of sounds due to the accompanying airflow limitation or to poor transmission of sounds due to destruction of parenchyma. Lung sound intensity was investigated in normal and emphysematous subjects in relation to airflow. METHODS: Eight normal men (45-63 years, FEV1 79-126% predicted) and nine men with severe emphysema (50-70 years, FEV1 14-63% predicted) participated in the study. Emphysema was diagnosed according to pulmonary history, results of lung function tests, and radiographic criteria. All subjects underwent phonopneumography during standardised breathing manoeuvres between 0.5 and 2 1 below total lung capacity with inspiratory and expiratory target airflows of 2 and 1 l/s respectively during 50 seconds. The synchronous measurements included airflow at the mouth and lung volume changes, and lung sounds at four locations on the right chest wall. For each microphone airflow dependent power spectra were computed by using fast Fourier transformation. Lung sound intensity was expressed as log power (in dB) at 200 Hz at inspiratory flow rates of 1 and 2 l/s and at an expiratory flow rate of 1 l/s. RESULTS: Lung sound intensity was well repeatable on two separate days, the intraclass correlation coefficient ranging from 0.77 to 0.94 between the four microphones. The intensity was strongly influenced by microphone location and airflow. There was, however, no significant difference in lung sound intensity at any flow rate between the normal and the emphysema group. CONCLUSION: Airflow standardised lung sound intensity does not differ between normal and emphysematous subjects. This suggests that the auscultatory finding of diminished breath sounds during the regular physical examination in patients with emphysema is due predominantly to airflow limitation. PMID- 1440460 TI - Effect of methacholine induced bronchoconstriction on the spectral characteristics of breath sounds in asthma. AB - BACKGROUND: Analysis of breath sounds by digital techniques offers an attractive non-invasive method of monitoring changes in airway calibre. Asthmatic breath sounds have been analysed and related to changes in forced expiratory volume in one second (FEV1). METHODS: Bronchoconstriction was induced with methacholine in six asthmatic subjects on two occasions and changes in FEV1 and breath sound spectra were measured. RESULTS: Audible wheeze appeared after a mean (SE) fall in FEV1 of 35% (6.3%) but the level was not reproducible within patients. The mean and median frequency of the spectra of breath sounds correlated with the percentage of predicted FEV1 (r = -0.5 and -0.6 respectively; p < 0.001). Inclusion of the quartile frequencies in a stepwise multiple regression reduced the residual variance by a further 9%. CONCLUSION: Detecting changes in airway calibre by this method of sound analysis so far produces qualitative data only and will not yield quantitative data in individual patients. PMID- 1440461 TI - A cost description of an adult cystic fibrosis unit and cost analyses of different categories of patients. AB - BACKGROUND: There is little information on the costs of running an adult cystic fibrosis centre. The aim of this study was to provide detailed costs to assist funding and planning for these patients. METHODS: The cost of a regional adult cystic fibrosis centre serving 119 cystic fibrosis patients, categorised according to four treatment regimens, was determined. District health authority, family health service authority, and voluntary resources used from April 1989 to March 1990 were determined, with appropriate bases for allocation of costs and patient based costs from local information. RESULTS: The total annual cost of treating the 119 patients was 980,646 pounds, with an average cost 8241 pounds per patient. An outpatient reviewed at three monthly intervals cost 2792 pounds a year; an outpatient receiving intravenous antibiotics cost 8606 pounds; an inpatient receiving intravenous antibiotics cost 13,501 pounds; and a patient needing a high level of care cost 19,955 pounds. Medication accounted for 57% (561,395 pounds) of the total cost. CONCLUSIONS: This analysis has helped us to secure funding for patients with cystic fibrosis and it facilitates the prediction of future requirements. The study also indicates the limitations of using average patient costs and difficulties as a result of the poorly structured British National Health Service accounting and information systems. PMID- 1440462 TI - Comparison of polymerase chain reaction amplification of two mycobacterial DNA sequences, IS6110 and the 65kDa antigen gene, in the diagnosis of tuberculosis. AB - BACKGROUND: Knowledge of the sequences of mycobacterial genes and the availability of DNA amplification techniques have raised the possibility that identification of mycobacterial DNA may offer a rapid and specific diagnostic test for tuberculosis. The correlation between the presence of Mycobacterium tuberculosis DNA and clinical tuberculosis, however, is not known. This study compared the results of polymerase chain reaction amplification of two M tuberculosis DNA sequences, IS6110 and the gene encoding the 65kDa heat shock protein (65kDa Ag), from sputum, bronchoscopy washings, and bronchoalveolar lavage fluid and related these findings to the presence of active and past tuberculosis. METHODS: Highly specific primers were used for amplification of IS6110 and 65kDa Ag DNA. Analysis was performed on one or more samples from 87 patients. RESULTS: IS6110 DNA was identified in samples from all six patients with active tuberculosis, from 15 to 18 patients with past tuberculosis, from five of nine contacts of patients with tuberculosis, and from nine of 54 patients with lung disease unrelated to tuberculosis. The 65kDa Ag DNA was identified in samples from all patients with active and past tuberculosis, from contacts of patients with tuberculosis, and from 14 of 42 patients with non-tuberculous lung diseases. CONCLUSION: These data suggest that the presence of IS6110 DNA correlates more closely with a tuberculosis related diagnosis than that of 65kDa Ag DNA and that both DNAs are found in most subjects with past tuberculosis or contacts of patients with tuberculosis. This may limit the clinical usefulness of these tests. PMID- 1440463 TI - Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG. AB - BACKGROUND: Macrophage activation by cytokines provides only a partial explanation of antimycobacterial immunity in man. Because cytolytic T lymphocytes have been shown to contribute to immunity in animal models of intracellular infection, the generation of mycobacterial antigen specific cytotoxic T cells was examined in the peripheral blood of patients with tuberculosis. METHODS: Subjects comprised 36 patients with active tuberculosis (18 newly diagnosed) and 32 healthy volunteers, of whom 25 had had BCG vaccination and seven were Mantoux negative. The ability of purified protein derivative (PPD) stimulated peripheral blood lymphocytes to lyse autologous, mycobacterial antigen bearing macrophages was examined by using a chromium 51 release assay. RESULTS: PPD stimulated lymphocytes from normal, Mantoux positive, BCG vaccinated subjects produced high levels of PPD specific cytolysis, whereas lymphocytes from unvaccinated, uninfected subjects caused little or no cytolysis. The generation of cytolytic T lymphocytes by patients with tuberculosis was related to their clinical state. Those with cavitating pulmonary disease or lymph node tuberculosis generated PPD specific lymphocytes with cytotoxic ability similar to that of those from Mantoux positive control subjects, whereas lymphocytes from patients with non-cavitating pulmonary infiltrates showed poor antigen specific cytolysis. After seven days of stimulation with PPD in vitro, lymphoblasts contained both CD4+ and CD8+ cells. Mycobacterial antigen specific cytolysis was restricted to the CD4+ cell population and was blocked by monoclonal antibodies directed against major histocompatibility class II (MHC) antigens. CONCLUSION: CD4+ cytolytic T cells can lyse autologous macrophages presenting mycobacterial antigen and were found in patients with cavitating pulmonary tuberculosis or tuberculous lymphadenitis and in normal, Mantoux positive control subjects. The ability to generate these T cell responses seems to be a marker for response to mycobacteria and may contribute to tissue damage in tuberculosis. These responses do not provide protective immunity against Mycobacterium tuberculosis but may help in disease localisation. PMID- 1440464 TI - Height and age adjustment for cross sectional studies of lung function in children aged 6-11 years. AB - BACKGROUND: No standard exists for the adjustment of lung function for height and age in children. Multiple regression should not be used on untransformed data because, for example, forced expiratory volume (FEV1), though normally distributed for height, age, and sex, has increasing standard deviation. A solution to the conflict is proposed. METHODS: Spirometry on representative samples of children aged 6.5 to 11.99 years in primary schools in England. After exclusion of children who did not provide two repeatable blows 910 white English boys and 722 girls had data on FEV1 and height. Means and standard deviations of FEV1 divided by height were plotted to determine whether logarithmic transformation of FEV1 was appropriate. Multiple regression was used to give predicted FEV1 for height and age on the transformed scale; back transformation gave predicted values in litres. Other lung function measures were analysed, and data on inner city children, children from ethnic minority groups, and Scottish children were described. RESULTS: After logarithmic (ln) transformation of FEV1 standard deviation was constant. The ratios of actual and predicted values of FEV1 were normally distributed in boys and girls. From the means and standard deviations of these distributions, and the predicted values, centiles and standard deviation scores can be calculated. CONCLUSION: The method described is valid because the assumption of stable variance for multiple regression was satisfied on the log scale and the variation of ratios of actual to predicted values on the original scale was well described by a normal distribution. The adoption of the method will lead to uniformity and greater ease of comparison of research findings. PMID- 1440465 TI - Nasal ventilation to facilitate weaning in patients with chronic respiratory insufficiency. AB - BACKGROUND: The non-invasive technique of nasal intermittent positive pressure ventilation (NIPPV) has an established role in providing domiciliary nocturnal ventilatory support in patients with chest wall disorders, neuromuscular disease, and chronic obstructive lung disease. NIPPV was used to simplify ventilatory management and assist the return of spontaneous breathing in patients with chronic respiratory insufficiency who had failed to wean from conventional intermittent positive pressure ventilation (IPPV). METHODS: A trial of NIPPV was carried out in 22 patients with weaning difficulties. Nine patients had chest wall disorders or primary lung disease, six had neuromuscular conditions, and seven had cardiac disorders with additional pulmonary disease. Conventional IPPV via an endotracheal tube or tracheostomy had been continued postoperatively in nine patients and 13 had been ventilated after acute cardiorespiratory decompensation. RESULTS: Conventional IPPV had been continued for a median of 31 days (range 2-219). Eighteen patients were successfully transferred to NIPPV and discharged home a median of 11 days (range 8-13) after starting this type of ventilation. Sixteen patients remain well 1-50 months after hospital discharge and 10 of these continue on domiciliary nocturnal NIPPV. Seven patients have returned to work. CONCLUSION: NIPPV can be used to facilitate the return of spontaneous breathing and to reduce the need for intensive care accommodation in patients with an acute exacerbation of chronic respiratory insufficiency that requires intubation and IPPV. PMID- 1440466 TI - Lung function testing in adults with preferential nasal breathing. AB - Three adult patients with asthma with preferential nasal breathing were found to have a typical pattern of lung function test results with substantial between test variation. This condition can be identified as a cause of unsatisfactory performance in respiratory tests by observing the patient's reaction after the nostrils have been occluded. PMID- 1440467 TI - Bronchopulmonary Kaposi's sarcoma in patients with AIDS. AB - BACKGROUND: Kaposi's sarcoma in HIV antibody positive patients may affect the lungs. This study describes the presentation, chest radiographic appearances, and pulmonary function test abnormalities in patients with AIDS who had tracheobronchial Kaposi's sarcoma. METHODS AND RESULTS: Twenty nine (8%) of 361 consecutive HIV antibody positive patients undergoing bronchoscopy for respiratory symptoms had tracheobronchial Kaposi's sarcoma. Eight patients had intercurrent infections and one had previously received chemotherapy for cutaneous Kaposi's sarcoma; these patients were excluded. Seven of the remaining 20 patients had localised Kaposi's sarcoma (lesions confined to the trachea or the subsegments of one lobe) and 13 had widespread Kaposi's sarcoma (affecting the trachea and one lobe or the subsegments of more than one lobe); 19 patients also had cutaneous and palatal Kaposi's sarcoma. Seven patients, four with widespread disease, had a normal radiograph. All patients had reduced transfer factor (TLCO) and transfer coefficient (KCO) but only those with widespread disease had reductions in forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). Follow up pulmonary function testing in seven patients (median three months later) showed further reductions in TLCO. All four patients who received no treatment had progressive radiographic abnormalities; bronchoscopy in two patients showed progressive tracheobronchial disease, and two patients had further reductions in FEV1 and FVC. In three patients treated with chemotherapy palliation of symptoms was achieved but two had further reductions in FEV1 and FVC and the radiograph deteriorated. Bronchoscopy showed regression of disease in only one patient. CONCLUSION: Pulmonary Kaposi's sarcoma produces abnormalities of TLCO even in patients with localised disease; airflow obstruction may occur in patients with widespread disease. Bronchoscopic reassessment of the extent of disease may not accurately reflect response to chemotherapy. PMID- 1440468 TI - Bronchopulmonary Kaposi's sarcoma in patients with AIDS. AB - BACKGROUND: Kaposi's sarcoma is the most common secondary neoplasm to complicate HIV infection and may cause pulmonary disease. METHODS: A prospective study was carried out in 140 consecutive patients who were HIV seropositive and required bronchoscopy for new respiratory symptoms of at least two weeks' duration, with either a chest radiographic abnormality or abnormality of pulmonary function. The patients were classified into those with single local endobronchial lesions of Kaposi's sarcoma or generalised widespread lesions. Before bronchoscopy all patients had routine simple pulmonary function tests and chest radiography. RESULTS: Thirty nine (21%) patients had evidence of cutaneous Kaposi's sarcoma. Nineteen of the 39 were found to have endobronchial Kaposi's sarcoma lesions at bronchoscopy, but none of those who did not have cutaneous Kaposi's sarcoma. Respiratory symptoms of cough and breathlessness and radiographic abnormalities were attributed to Kaposi's sarcoma in this group, except in four patients who had concomitant pneumocystis pneumonia. Eight patients had local endobronchial Kaposi's sarcoma lesions and 11 had extensive lesions. Patients with extensive lesions had more widespread radiographic abnormalities; four of the patients with local endobronchial lesions had normal chest radiographs. All patients had reduced transfer factor for carbon monoxide and transfer coefficient, whereas patients with extensive endobronchial lesions also had reductions in forced expiratory volume in one second and forced vital capacity. Median survival (with palliative chemotherapy with vincristine and bleomycin) was only seven months. In three patients who needed further diagnostic bronchoscopy endobronchial lesions had regressed while they were having chemotherapy. CONCLUSIONS: This study suggests that endobronchial Kaposi's sarcoma is a relatively common finding in patients with AIDS and is particularly common in patients with cutaneous Kaposi's sarcoma who present with respiratory illness. Endobronchial Kaposi's sarcoma causes respiratory disease and abnormalities of pulmonary function. Pulmonary Kaposi's sarcoma should be considered as a possible cause for respiratory illness in any patient with cutaneous Kaposi's sarcoma. PMID- 1440469 TI - Pulmonary Kaposi's sarcoma in Africa. AB - BACKGROUND: A study was carried out to identify the main clinical radiological and bronchoscopic features of HIV related Kaposi's sarcoma of the lung in African patients. METHODS: Forty seven HIV positive patients with epidemic Kaposi's sarcoma who had clinical or radiological respiratory changes were investigated by simple lung function tests and fibreoptic bronchoscopy. RESULTS: The most common respiratory symptoms in the 47 patients were persistent cough in 42, haemoptysis in 23, and breathlessness in 38. A restrictive spirometric pattern was most common. The mean (SD) forced expiratory volume in one second (FEV1) was 1.88 (0.62) 1 with a forced vital capacity (FVC) of 2.66 (0.87) 1 and a FEV1/FVC% of 73.2 (7.5). On the chest radiograph 26 patients had diffuse reticulonodular shadows, 11 focal nodular shadows, seven a pleural effusion, and one a substantial increase in vascular markings; in two the radiograph was normal. At bronchoscopy characteristic discrete lesions were easily visible in 37 patients and were often bright red. Multiple nodules were seen in 11, flat or early plaque lesions in 12 (14 had both), proximal flat lesions and diffuse infiltration in three, diffuse infiltration alone in four, and masses in two; one had normal appearances at bronchoscopy. One patient had Pneumocystis carinii and two had a single bacterial pathogen cultured from the bronchoalveolar lavage fluid. Only two of 29 bronchoscopic biopsies showed classical histological Kaposi's sarcoma. After cytotoxic treatment 20 patients have died, with an overall median survival of 70 days. CONCLUSION: In this African population symptomatic pulmonary Kaposi's sarcoma was common, with lesions seen in all but one patient at bronchoscopy. Coexistent infection was uncommon. Prognosis was poor despite treatment. PMID- 1440470 TI - An audit of the clinical investigation of pleural effusion. AB - BACKGROUND: Pleural aspiration with pleural biopsy is advised for the investigation of pleural effusion. The clinical investigation of pleural effusion in a group of teaching hospitals was audited with reference to adequacy and diagnostic value of sampling procedures. METHODS: A retrospective review of case records of all patients investigated for pleural effusion during an eight month period was performed. The records of 112 patients, age range 16-91 years, who underwent 150 procedures were reviewed. RESULTS: Microbiology samples were obtained from 137 procedures, of which five provided a positive culture, including one for mycobacteria. Cytology samples were obtained from 145 procedures though approximately two thirds of samples were less than the recommended 30 ml. The pleural biopsy rate was 30%, varying from 0% in general or thoracic surgery to 68% in thoracic medicine (thoracic surgeons carried out thoracoscopy). Twenty nine per cent of pleural biopsy samples were of poor quality. The complication rate was 2% for aspiration alone, and 4% for aspiration plus biopsy. The sensitivity of the first diagnostic procedure for a diagnosis of malignancy or tuberculosis was 53% for cytology alone, 50% for biopsy alone and 72% for cytology plus biopsy. CONCLUSION: The samples obtained from pleural aspiration and biopsy in the initial investigation of pleural effusion are often inadequate. Further education is necessary to improve the quantity and quality of specimens submitted for histological and cytological examination. PMID- 1440471 TI - High resolution computed tomography as a predictor of lung histology in systemic sclerosis. AB - BACKGROUND: The relative proportions of fibrosis and inflammation seen by open lung biopsy examination is a predictor of disease outcome in fibrosing alveolitis. This study was designed to assess the ability of high resolution computed tomography to predict the histological appearance of open lung biopsy specimens from patients with systemic sclerosis. METHODS: Twenty abnormal biopsy specimens from 12 patients were assessed; abnormalities were categorised as fibrotic (fibrosis exceeding inflammation) or inflammatory (inflammation equal to or exceeding fibrosis). Computed tomography appearances were scored for the lobe from which the biopsy specimen was taken; scans were graded from parenchymal opacification alone through to a reticular pattern alone. RESULTS: Two lobar appearances were identified on computed tomograms: amorphous parenchymal opacification equal in extent to reticulation (grade 3) and a predominantly reticular pattern (grade 4). There was a significant association between a fibrotic histological appearance and a grade 4 computed tomogram, and between an inflammatory histological appearance and a grade 3 computed tomogram. Computed tomography grade 4 was associated with a fibrotic histological appearance in 12 out of 13 lobes, and grade 3 with an inflammatory histological appearance in four out of seven lobes. CONCLUSION: Computed tomography discriminated between biopsy specimens that were predominantly fibrotic and a smaller group with a larger amount of inflammation. PMID- 1440472 TI - The pulmonary physician and critical care. 4. A new look at the pulmonary circulation in acute lung injury. PMID- 1440474 TI - Percutaneous visceral pleural biopsy with fenestrated cup biopsy forceps. AB - When there is an exudative pleural effusion often both the parietal and the visceral pleura are affected, but the usual practice is to perform a percutaneous parietal pleural biopsy alone for diagnosis. Percutaneous visceral pleural biopsy was carried out in 20 patients with exudative pleural effusions with fenestrated cup biopsy forceps. In all 20 biopsies pleural tissue was obtained and it was diagnostic in 19 cases. The procedure is painless and appears safe. PMID- 1440473 TI - The airway microvasculature and exercise induced asthma. AB - It has been proposed that exercise induced asthma is a result of "rapid expansion of the blood volume of peribronchial plexi" (McFadden ER, Lancet 1990;335:880-3). This hypothesis proposes that the development of exercise induced asthma depends on the thermal gradient in the airways at the end of hyperpnoea. The events that result in exercise induced asthma are vasoconstriction and airway cooling followed by reactive hyperaemia. We agree that the airway microcirculation has the potential for contributing to the pathophysiology of exercise induced asthma. We do, however, question whether reactive hyperaemia, in response to airway cooling, is the mechanism whereby hyperpnoea provokes airways obstruction in asthmatic patients. Further, we question whether vasoconstriction accompanies dry air breathing and whether an abnormal temperature gradient and rapid rewarming of the airways are prerequisites for exercise induced asthma. From published experiments we conclude that dry air breathing is associated with vasodilation and increase in airway blood flow rather than vasoconstriction and a decrease in blood flow to the airways. We propose that the stimulus for the increase in airway blood flow is an increase in osmolarity of the airway submucosa. This osmotic change is caused by the movement of water to the airway lumen in response to evaporative water loss during hyperpnoea. The increase in airway blood flow may occur directly or indirectly by the osmotic release of mediators. Exercise induced asthma is most likely to be due to the contraction of bronchial smooth muscle caused by the same mediators. Whether it is enhanced or inhibited by alterations in airway blood flow is not yet established in man. PMID- 1440475 TI - Acute and long term respiratory damage following inhalation of ammonia. AB - A lifelong non-smoker who was the victim of a massive accidental exposure to anhydrous ammonia gas was followed up for 10 years. In the acute phase the patient presented with severe tracheobronchitis and respiratory failure, caused by very severe burns of the respiratory mucosa. After some improvement he was left with severe and fixed airways obstruction. Isotope studies of mucociliary clearance, computed tomography, and bronchography showed mild bronchiectasis. It is concluded that acute exposure to high concentrations of ammonia may lead to acute respiratory injury but also to long term impairment of respiratory function. PMID- 1440476 TI - Expandable metal stents for tracheal obstruction: permanent or temporary? A cautionary tale. AB - An expandable metal stent inserted via a long term tracheostomy successfully relieved life threatening respiratory obstruction due to benign tracheal stenosis. Later the patient's tracheostomy suction catheter became stuck on the stent and dislodged it. The stent was removed electively, without damaging the trachea, with a rigid biopsy forceps. PMID- 1440477 TI - Occupational asthma due to polyethylene shrink wrapping (paper wrapper's asthma). AB - Occupational asthma due to the pyrolysis products of polyvinyl chloride (PVC) produced by shrink wrapping processes has previously been reported. The first case of occupational asthma in a shrink wrap worker using a different plastic, polyethylene, is reported; the association was confirmed by specific bronchial provocation testing. PMID- 1440478 TI - Occupational asthma induced by the fungicide tetrachloroisophthalonitrile. AB - A 48 year old male farmer had recurrent episodes of dyspnoea, shortness of breath, and wheezing after being in his plastic greenhouse when the fungicide tetrachloroisophthalonitrile had been sprayed. A bronchial provocation test with a control challenge and a patch skin test confirmed that his asthma was induced by tetrachloroisophthalonitrile. PMID- 1440479 TI - Alternative and complementary medicine for asthma. PMID- 1440480 TI - Alternative and complementary medicine for asthma. PMID- 1440481 TI - Air pollution and respiratory morbidity. PMID- 1440482 TI - Pulmonary function in chronic renal failure: effects of dialysis and transplantation. PMID- 1440483 TI - Haematological effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in man. PMID- 1440484 TI - Apparent lack of synergism between heparin and dihydroergotamine in prevention of deep vein thrombosis after elective hip replacement: a randomised double-blind trial reported in conjunction with an overview of previous results. AB - We report the results of a double-blind, randomised trial of venous thrombosis (VT) prevention in 117 patients having elective hip replacement where low dose heparin alone (5,000 IU sodium heparin given subcutaneously [sc] 8 hourly until the seventh postoperative day) was compared with low dose heparin plus dihydroergotamine (DHE; 0.5 mg, given 8 hourly by sc injection). The trial end point consisted of VT discovered through bilateral ascending venography done routinely on the seventh postoperative day. VT developed in 34% of patients given heparin/DHE (95% confidence interval = 22% - 47%) compared with 24% in those given low dose heparin alone (95% confidence interval = 14% - 37%; p = 0.34), difference = 10% (95% confidence interval = -7% to +26%). Corresponding figures for the incidence of proximal (above-knee) thrombosis were 17% and 14% (95% confidence intervals = 8% - 29% and 6% - 25% respectively). These results are discussed in the context of a detailed overview of published evidence concerning VT prevention with heparin/DHE after hip replacement and we conclude it is unlikely that heparin/DHE is markedly superior to low dose heparin alone in this clinical setting. PMID- 1440485 TI - Ventilation-perfusion lung scanning and the diagnosis of pulmonary embolism: improvement of observer agreement by the use of a lung segment reference chart. AB - OBJECTIVE: To test the hypothesis that the systematic use of a lung segment reference chart can improve the inter- and intra-observer agreement for the interpretation of ventilation-perfusion lung scans. DESIGN: A randomized trial. STUDY POPULATION: Ventilation-perfusion lung scans were obtained in a series of 220 consecutive patients with clinically suspected pulmonary embolism. INTERVENTION: Ventilation-perfusion scans were randomly allocated to one of two series each consisting of 110 ventilation-perfusion lung scans. The first series of lung scans was interpreted according to the routine diagnostic approach, and the second series was interpreted with the mandatory use of a lung segment reference chart on which observed ventilation and perfusion defects were drawn. The two nuclear medicine physicians agreed a priori on the diagnostic criteria of the classification scheme. MEASUREMENTS: Lung scans were classified as normal, non-high probability, or high probability for pulmonary embolism. The extent of disagreement between the nuclear medicine physicians (inter-observer disagreement) and the lack of internal consistency of each nuclear medicine physician (intra-observer disagreement) was assessed by the percentage disagreement and by kappa statistic. RESULTS: Inter-observer disagreement which was 20% in the first series, decreased significantly in the second series to 7%; P = 0.003. Intra-observer disagreement for the first series was 10% and 22% for the nuclear medicine physicians, respectively. Intra-observer disagreement for the second series of lung scans decreased significantly for one nuclear medicine physician (intra-observer disagreement, 0%; P less than 0.01), whereas intra observer disagreement was reduced to 10% for the other nuclear medicine physician (P = 0.09). CONCLUSION: Inter- and intra-observer disagreement were significantly reduced when two nuclear medicine specialists interpreted ventilation-perfusion lung scans according to the routine diagnostic approach plus the use of a lung segment reference chart. The use of the lung segment reference chart for the interpretation of lung scans is likely to improve the management of patients with clinically suspected pulmonary embolism. PMID- 1440486 TI - Early activation of hemostasis during cardiopulmonary bypass: evidence for thrombin mediated hyperfibrinolysis. AB - In 14 consecutive patients undergoing cardiopulmonary bypass for coronary bypass surgery the time course of coagulation and fibrinolysis markers were measured, e. g. plasma levels of thrombin-antithrombin III (TAT) complexes, cross-linked fibrin degradation products (XIFDP) and plasmin-alpha 2-antiplasmin complexes (PAP). TAT levels exceeded the 90% baseline percentile already during CPB (after opening of aortic clamp) in 10 patients, whereas PAP and XIFDP exceeded their 90% percentile in only one patient at this time. Concerning fibrinolysis markers PAP and XIFDP the majority of patients showed elevations higher than their 90% baseline percentile only 1 h postoperation. Correlation analysis revealed significant dependencies between TAT levels during and at the end of CPB and PAP levels 1 h postoperation (R = 0.55 and R = 0.56 respectively). Furthermore, 1 h postoperation XIFDP levels were significantly correlated with both TAT and PAP. Peak XIFDP levels at the same time correlated with blood loss via thoracic drains (R = 0.56). Thus, we suggest that hyperfibrinolysis in patients undergoing CPB is at least partly due to hypercoagulation. Clinically, this may implicate that intensified anticoagulation could prevent hyperfibrinolysis and reduce postoperative blood loss. PMID- 1440487 TI - The effect of insulin treatment on the balance between tissue plasminogen activator and plasminogen activator inhibitor-1 in type 2 diabetic patients. AB - Beside hypercoagulation and hyperactivated platelets disturbances of the fibrinolytic system towards hypofibrinolysis have been reported to be associated with both glycemic and lipidemic derangement in diabetic patients. In the present prospective follow-up study the effect of 16 weeks insulin treatment and glycemic regulation on plasma levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1), the main regulators of fibrinolysis, was investigated in 19 type-2 diabetic patients with secondary failure to sulphonylureas. A similar glycemic regulation was obtained in a control group of 10 type 2 diabetic patients with sufficient metabolic response to strict dietary treatment and continuation of sulphonylurea treatment. Compared to 27 healthy subjects levels of tPA and PAI-1 were not significantly increased in type 2 diabetic patients before metabolic intervention. Although a hypofibrinolytic state due to an increase of PAI-1 levels was previously reported in obese hyperinsulinemic patients, no effect of insulin treatment on both tPA- and PAI-1 levels was observed in the present study including patients with only slightly increased body mass index (median 26.0 kg/m2). By correlation analysis PAI-1 levels were significantly related to serum cholesterol (R = 0.52) and glycemic control (glucose R = 0.41) in the whole group of diabetic patients at entry and in both subgroups after 16 weeks of treatment (insulin group: cholesterol R = 0.46, HbA1c R = 0.51; sulphonylurea group: cholesterol R = 0.59, HbA1c R = 0.58). In healthy subjects tPA and PAI-1 was correlated to serum insulin (R = 0.54, R = 0.56) and triglycerides (R = 0.46, R = 0.40).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440488 TI - Detection of asymptomatic deep vein thrombosis by real-time B-mode ultrasonography in hip surgery patients. AB - The aim of this study was to prospectively evaluate the accuracy of real-time B mode ultrasonography in the diagnosis of asymptomatic proximal deep vein thrombosis (DVT) in hip surgery patients. Venography was adopted as the gold standard. We studied 100 consecutive patients undergoing hip surgery: 60 patients for hip fracture and 40 patients for elective hip replacement. Bilateral real time B-mode ultrasonography was performed prior to bilateral venography. The two diagnostic procedures were performed on the same day by different investigators unaware of the assigned prophylatic regimen for DVT. Compressibility of the vein segment was adopted as the single criterion for DVT. Venography was performed and judged by radiologists unaware of the ultrasonography results. In 13 limbs venography was either impossible to perform or not adequate for judgement. Ultrasonography and an adequate venography was obtained in 187 limbs. A venography proven DVT was observed in 49 limbs (26.2%) and a proximal DVT in 21 limbs (11.2%). All the patients were asymptomatic for DVT. The sensitivity and specificity of real time B-mode ultrasonography for proximal DVT were 57% (95% confidence interval: C.I. 36-80) and 99% (C.I. 99-100), respectively and the positive and negative predictive values were 93% (C.I. 73-100) and 95% (C.I. 91 97), respectively. The sensitivity and specificity for overall DVT were 25% (C.I. 11-38) and 99% (C.I. 97-100), respectively and the positive and negative predictive values were 92% (C.I. 73-100) and 79% (C.I. 76-85), respectively. Our data indicate that real-time B-mode ultrasonography for its high specificity could make venography unnecessary in patients with positive results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440489 TI - A six year prospective study of fibrinogen and other risk factors associated with mortality in stable claudicants. AB - A total of 333 patients with stable intermittent claudication at recruitment were followed up for 6 years to determine risk factors associated with subsequent mortality. Cardiovascular diseases were the underlying cause of death in 78% of the 114 patients who died. The strongest independent predictor of death during the follow-up period was the plasma fibrinogen level, an increase of 1 milligram being associated with a nearly two-fold increase in the probability of death within the next 6 years. Age, low ankle/brachial pressure index and a past history of myocardial infarction also increased the probability of death during the study period. The plasma fibrinogen level is a valuable index of those patients with stable intermittent claudication at high risk of early mortality. The results also provide further evidence for the involvement of fibrinogen in the pathogenesis of arterial disease. PMID- 1440490 TI - Immunoglobulin fractions isolated from patients with antiphospholipid antibodies prevent the inactivation of factor Va by activated protein C on human endothelial cells. AB - We studied the effect of purified immunoglobulins (Ig) from 21 patients with antiphospholipid antibodies (aPL) on factor Va degradation by activated protein C (aPC) on cultured human umbilical vein endothelial cells (HUVEC). Sera from patients were tested on an ELISA aPL assay to determine the isotype with aPL activity. HUVEC were incubated with purified IgG or IgM fraction from controls or patients. Activated PC and factor Va were then added and factor Va degradation was measured after several reaction times. 13 of 14 IgM and 8 of 10 IgG from patients showed an inhibitory effect on factor Va degradation by aPC when compared with control Ig. We also observed the same inhibitory effect with patients' Ig on studying the degradation of factor Va by aPC in a purified system containing aPC, protein S and phospholipids. These results suggest that aPL antibodies disturb the anticoagulant activity of aPC, which may contribute to the thrombotic tendency of these patients. PMID- 1440491 TI - A rapid monoclonal antibody-based enzyme immunoassay (EIA) for the quantitative determination of soluble fibrin in plasma. AB - Soluble fibrin is considered as a molecular marker for intravascular fibrin formation, and impending thrombotic events. Most of the existing assays are less suitable for routine clinical applications and their specificity may be limited. We have developed a sandwich-type EIA with a fibrin-specific MoAb described by us before (Proc Natl Acad Sci 1989; 86: 8951) as the capture antibody. An other MoAb (G8; Thromb Haemostas 1988; 60: 145) with an epitope in the carboxyl-terminal sections of the fibrin alpha-chains, was labeled with peroxidase and used as the tagging antibody. The EIA is calibrated against plasma spiked with known concentrations of soluble fibrin. The time-to-result of the EIA is only 1.5 h. Concentrations as low as 0.5 micrograms soluble fibrin/ml plasma are readily measureable. Heparin has no effect on the results. Fibrinogen and fibrin(ogen) degradation products are not detected. The values of fibrinopeptide A and soluble fibrin values found with the "COA-SET soluble fibrin" assay correlated well with the soluble fibrin values found with our EIA i.e. r = 0.998 and 0.984, respectively. The run-to-run variabilities were 7.9% and 6.6% for samples with low and high soluble fibrin concentrations, respectively. The within-run variabilities were 2.5, 1.8, 4.0 and 4.6% for samples with 1, 0.5, 0.25 and 0.125 micrograms soluble fibrin/ml, respectively. The sensitivity, specificity, accuracy and short time-to-result make our EIA suitable for routine clinical applications and the monitoring of the effectivity of heparinization. PMID- 1440492 TI - Antiphospholipid antibody positive sera enhance endothelial cell procoagulant activity--studies in a thrombosis model. AB - The effect of sera and IgG from 12 patients with systemic lupus erythematosus (SLE) on the endothelial cell (EC) procoagulant activity (PCA) was investigated in an in vitro thrombosis model. Six of the 12 SLE sera contained antiphospholipid antibodies (aPL). EC were stimulated for 8 h at 37 degrees C with or without 50 pM tumor necrosis factor (TNF) in culture medium containing 20% patient or control serum. Then the endothelial cell matrix (ECM) was isolated and subsequently exposed in a perfusion chamber to circulating normal whole blood, anticoagulated with low molecular weight heparin (LMWH). The PCA of the ECM was determined as the amount of generated fibrinopeptide A (FPA) in samples taken before and after perfusion. Furthermore, cross sections were made of the perfused matrix and analyzed for platelet adhesion and aggregate formation. All six aPL containing sera induced a small, but significant increase of ECM procoagulant activity. When added in combination with a low dose of TNF (50 pM), a synergistic enhancement of ECM procoagulant activity was found. The FPA generation was increased to 150-614% from the values obtained after stimulation with TNF and control serum. Also a shift towards the formation of larger platelet thrombi was observed. After stimulation with TNF and patient serum the surface of ECM covered with large aggregates (greater than 5 microns) was increased by 124 329% compared to the results obtained after stimulation with control serum and TNF. When patient sera were depleted from IgG the effects were strongly decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440493 TI - The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism. AB - One hundred and three patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (FXII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with FXII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined FXII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were divided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in FXII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of FXII deficiency was significantly higher (20%, p less than 0.003). In 67% of the patients with FXII deficiency a positive family history of thrombosis could be established. In contrast, only 32% of all venous and 28% of all arterial thrombosis patients had a positive family history. We believe that reduced levels of FXII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of FXII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction. PMID- 1440494 TI - Molecular cloning and cell-free expression of mouse antithrombin III. AB - The homology between antithrombin III (AT-III) of mouse, of man, and that of other species was investigated. Preliminary experiments showed that mouse AT-III inhibited human alpha-thrombin efficiently (second order rate constant [K2nd] 5.8 x 10(3) M-1 s-1) as compared to human AT-III (K2nd 6.7 x 10(3) M-1), but was not recognized on immunoblots by antibodies that recognized both human and rabbit AT III. In order to compare AT-III from different species at the molecular level, a cDNA clone for murine AT-III was isolated from a lambda ZAP mouse liver cDNA library on the basis of hybridization to a rabbit AT-III cDNA probe. The 1509 bp murine AT-III cDNA consists of a 1398 bp open reading frame, preceded by a 15 bp 5' untranslated region, followed by a 75 bp 3' untranslated region. The deduced primary protein structure consists of a 32 amino acid signal sequence, with a mature portion of 433 residues. Mature murine AT-III is 89% identical to its human counterpart, 86% identical to bovine AT-III, and 82% identical to that of the rabbit. Constructs lacking the nucleotides encoding the signal sequence were engineered and expressed in a cell-free system. The resulting 47 kDa non glycosylated translation product was capable of being cleaved by human alpha thrombin, of forming SDS-stable complexes with the protease, and of binding to immobilized heparin. Isolation of the murine AT-III cDNA will make feasible molecularly defined experiments with murine AT-III in the mouse system. PMID- 1440495 TI - Anticoagulant activity of beta 2-glycoprotein I is potentiated by a distinct subgroup of anticardiolipin antibodies. AB - Plasmas of 16 patients positive for both IgG anticardiolipin (aCL) antibodies and lupus anticoagulant (LA) antibodies were subjected to adsorption with liposomes containing cardiolipin. In 5 of these plasmas both the anticardiolipin and the anticoagulant activities were co-sedimented with the liposomes in a dose dependent manner, whereas in the remaining cases only the anticardiolipin activity could be removed by the liposomes, leaving the anticoagulant activity (LA) in the supernatant plasma. aCL antibodies purified from the first 5 plasmas were defined as aCL-type A, while the term aCL-type B was used for antibodies in the other 11 plasmas, from which 2 were selected for this study. Prolongation of the dRVVT was produced by affinity-purified aCL-type A antibodies in plasma of human as well as animal (bovine, rat and goat) origin. aCL-type B antibodies were found to be devoid of anticoagulant activity, while the corresponding supernatants containing LA IgG produced prolongation of the dRVVT only in human plasma. These anticoagulant activities of aCL-type A and of LA IgG's were subsequently evaluated in human plasma depleted of beta 2-glycoprotein I (beta 2 GPI), a protein which was previously shown to be essential in the binding of aCL antibodies to anionic phospholipids. Prolongation of the dRVVT by aCL-type A antibodies was abolished using beta 2-GPI deficient plasma, but could be restored upon addition of beta 2-GPI. In contrast, LA IgG caused prolongation of the dRVVT irrespective of the presence or absence of beta 2-GPI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440496 TI - A comparison of methods for the measurement of activated factor VII. AB - A number of different methods are available for the measurement of factor VIIa. Almost all of these employ ratios of two different measurements of factor VII. In order to determine which is the most sensitive to activated factor VII we have compared currently available methods in the following groups: two patients with haemophilia A following treatment with activated recombinant factor VII (rVIIa); 6 normal plasmas during cold promoted activation of factor VII; normal individuals (n = 23); and patients with unequivocal disseminated intravascular coagulation (DIC, n = 19). Factor VII was measured in an amidolytic assay (VII:Amid) and an antigen assay (VII:Ag). Clotting activity was measured using rabbit (VII:C Rab), human (VII:C Hum) and bovine (VII:C Bov) thromboplastin. Of the clotting assays the most sensitive to the presence of factor VIIa was that which utilised bovine thromboplastin. Amidolytic and immunological measurements were unaffected by the activity state of factor VII. The ratios VII:C Rab/VII:Ag and VII:C Rab/VII:Amid were insensitive to activated factor VII. The ratios most sensitive to the presence of factor VIIa were VII:C Bov/VII:Amid and VII:C Bov/VII:Ag. The ratios VII:C Bov/VII:C Rab and VII:C Bov/VII:C Hum are less sensitive but have the advantage for epidemiological studies of narrower reference ranges. PMID- 1440497 TI - Effect of DDAVP on endotoxin-induced intravascular coagulation in rabbits. AB - We have evaluated the effect of 1-Deamino-8D-arginine vasopressin (DDAVP) on an experimental model of intravascular coagulation (DIC) induced in rabbits by injection of 20 micrograms kg-1 h-1 during 6 h of E. coli lipopolysaccharide. DDAVP significantly ameliorated the platelet drop and fibrinogen decrease (p less than 0.01) induced by endotoxin in control animals. A significant reduction in factor XII consumption (p less than 0.01) and a decrease in the generation of endotoxin induced PAI-1 activity in rabbits circulation was also observed (p less than 0.005). Moreover, fibrin deposition in kidneys of rabbits receiving DDAVP was significantly reduced as compared to control animals. Finally, the mortality rate in the control group was significantly higher than in DDAVP-treated rabbits (p less than 0.01). The hemostatic changes induced by DDAVP correlated with lower fibrin deposition and reduction in mortality rates. PMID- 1440498 TI - Tissue plasminogen activator release in chronic venous hypertension due to heart failure. AB - In order to study the effects of chronic venous hypertension due to heart failure on blood fibrinolytic activity, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen, t-PA activity and PAI activity were measured before and after venous occlusion of the arm for 20 min in 15 patients with right-sided heart failure, 15 patients with left-sided heart failure, and 30 control healthy subjects. Central venous pressure, measured by observing the jugular veins, was above 15 cm of the blood column in all patients with right-sided heart failure, and normal (below 8 cm) in all patients with left sided heart failure and control subjects. There was no difference in the basal concentrations of t-PA (11.0, 10.2 and 10.8 ng/ml; all values medians) and PAI-1 antigens and their activities between right and left-sided heart failure and the control subjects. After the occlusion, t-PA antigen increased significantly less in right-sided heart failure (28.6 ng/ml) than in left-sided heart failure and the control subjects (54.5 and 45.9 ng/ml, respectively). It was concluded that the poor increase in fibrinolytic activity that had already been reported in patients with heart failure, was due to low t-PA release during occlusion and not to a high basal PAI level. It was limited to the patients with right-sided heart failure and was probably the consequence of chronic systemic venous hypertension. PMID- 1440499 TI - Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. AB - Although thrombolytic drugs have been extensively used in adults, there is sparse information on their effectiveness in newborns whose fibrinolytic system differs significantly from adults. The purpose of this study was to determine if low plasma levels of plasminogen in cord plasma limited the therapeutic effectiveness of thrombolytic agents. Urokinase (UK), streptokinase (SK) and tissue plasminogen activator (TPA) were compared for their ability to lyse washed 125I-labelled adult or cord fibrin clots suspended in cord or adult plasma. 125I-labelled fibrin clots were prepared by recalcifying cord or adult plasma spiked with labelled fibrinogen and then placed into cord or adult plasma which contained either saline or differing amounts of a specific thrombolytic agent. After a 60 min incubation, the remaining 125I-fibrin in clots released 125I-fibrin fragments, and concentrations of fibrinogen, alpha 2-antiplasmin, and plasminogen in the bathing plasma were measured and compared to starting values. Cord fibrin clots were more resistant than adult fibrin clots to all thrombolytic drugs tested (p less than 0.001). On average, the cord system retained 27% more 125I fibrin in clots, and released 32% less 125I-fibrin fragments into plasma. Fibrinogenolysis was also decreased in cord plasmas compared to adult plasmas. The degree of fibrinolysis and fibrinogenolysis in cord plasma increased to adult values when plasminogen concentrations were increased in the bathing plasma. Thus, cord fibrin clots have an impaired response to thrombolytic agents secondary to low levels of plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440500 TI - Thrombolytic activity of two chimeric recombinant plasminogen activators (FK2tu PA and K2tu-PA) in rabbits. AB - The aim of this study was to evaluate the thrombolytic activity of two hybrid plasminogen activators (HPAs) in a rabbit jugular vein thrombosis model. In the two HPAs the kringle-2 domain (K2tu-PA) or the finger and the kringle-2 domains (FK2tu-PA) of tissue-type plasminogen activator (t-PA) are linked to the catalytic protease domain of single chain urokinase type plasminogen activator (scu-PA). The two HPAs were compared with rt-PA and scu-PA on a weight/weight basis. K2tu-PA, FK2tu-PA, rt-PA and scu-PA were infused at doses of 0.4, 0.8 and 1.2 mg/kg over 3 h. Saline served as control. Saline produced 11 +/- 2% thrombolysis. The three doses of K2tu-PA led to 38 +/- 4%, 66 +/- 5% and 89 +/- 7% thrombolysis, respectively; the three doses of FK2tu-PA: 18 +/- 3%, 29 +/- 5% and 33 +/- 6%, respectively; the three doses of rt-PA 32 +/- 2%, 49 +/- 3% and 68 +/- 6%, respectively; the three doses of scu-PA 16 +/- 2%, 24 +/- 3% and 32 +/- 4%, respectively. K2tu-PA and rt-PA showed a statistically significant higher thrombolytic activity than FK2tu-PA and scu-PA at the three tested doses (p less than 0.01). The thrombolytic activity of K2tu-PA was significantly higher than rt PA at the two higher doses (p less than 0.01). Both K2tu-PA and rt-PA produced a statistically significant reduction of fibrinogen, alpha 2-antiplasmin and plasminogen 3 h after the start of the infusions of the two higher doses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440501 TI - Synergistic antithrombotic properties of G4120, a RGD-containing synthetic peptide, and argatroban, a synthetic thrombin inhibitor, in a hamster femoral vein platelet-rich thrombosis model. AB - The synergistic antithrombotic properties of G4120, a synthetic Arg-Gly-Asp (RGD) containing peptide which strongly inhibits platelet aggregation, and of Argatroban, a synthetic thrombin inhibitor, were examined in a reproducible quantitative hamster femoral vein platelet-rich mural thrombosis model. Bolus injections of G4120 and Argatroban inhibit thrombus formation in a dose-dependent way; 50% inhibition (ID50) is obtained with 11 micrograms/kg G4120 and with 2 mg/kg Argatroban. Combined bolus injections of 3 micrograms/kg G4120 with 0.5, 0.75 or 1 mg/kg Argatroban and of 1 mg/kg Argatroban with 1.5 or 3 micrograms/kg G4120 caused linear dose-dependent inhibition of thrombus formation, whereas 3 micrograms/kg G4120 or 1 mg/kg Argatroban alone had very little effect (less than 20% inhibition). ID50 was obtained with the combination of 3 micrograms/kg G4120 and 0.5 mg/kg Argatroban, corresponding to an equi-effective fractional combination of 0.62 with a 95% confidence interval of 0.50 to 0.74. Alternatively the ID50 was obtained with the combination of 1 mg/kg Argatroban and 1.3 micrograms/kg G4120, corresponding to an equi-effective fractional combination of 0.52 with a 95% confidence interval of 0.18 to 0.86. In both instances these results are indicative of a significant synergistic interaction. Bolus injection of 10 mg/kg aspirin, 100 U/kg heparin or the combination did not inhibit thrombus formation. The synergistic effect of the combination of platelet inhibiting RGD peptides and synthetic thrombin inhibitors could be useful in the prevention of arterial occlusion with platelet-rich thrombus in patients with ischemic heart disease following thrombolytic therapy or angioplasty, although this combination is not expected to reverse platelet thrombus formation. PMID- 1440502 TI - Mass contents of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol in human platelets stimulated with a thromboxane analogue and thrombin. AB - Mass contents of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG) were measured in U46619-stimulated human platelets. 1 microM of U46619 induced maximum responses in aggregation, 5-hydroxytryptamine (5HT) secretion and increase in intracellular free Ca2+ concentration ([Ca2+]i). Aggregation was almost comparable to that induced by maximal dose (1 U/ml) of thrombin, while 5HT release was almost half. The initial [Ca2+]i peak in response to U46619 was about half of thrombin stimulation. Production of IP3 and DG was, however, less than one tenth of that seen in thrombin stimulation. The profile (time course and concentration-dependency) of IP3 formation did not correlate with that of [Ca2+]i, suggesting that U46619 stimulates IP3-dependent and -independent Ca2+ mobilization. DG production was small but sustained for more than 5 min. These findings support the recent hypothesis that aggregation is regulated by a delayed accumulation of DG. The low level of 5HT secretion could be explained by the low production of second messengers, IP3 and DG. PMID- 1440503 TI - Effect of stimulation on the stabilization of platelet-fibrinogen interactions. AB - The interaction between fibrinogen and stimulated platelets is a multiphasic process that culminates in the stabilization of ligand binding and reduced accessibility of bound fibrinogen to exogenous antibody. The present study was designed to further explore platelet-fibrinogen interactions by examining the effect of agonist on bound fibrinogen expression and interaction with stimulated platelets as a function of time after ligand binding. Two agents were identified, Zn2+ and phorbol myristate acetate (PMA), which support progressive decreases in bound fibrinogen expression on platelets, but fail to support the stabilization of fibrinogen binding. Sixty min after binding to platelets, approximately 80% of bound fibrinogen remained reversibly associated with Zn(2+)- or PMA-treated platelets and failed to associate with the Triton X-100 insoluble cytoskeleton. In contrast, polyclonal anti-fibrinogen antibody binding decreased by more than 66%. Over the same time course, fibrinogen binding to control platelets, stimulated with thrombin or ADP, was not only accompanied by a 70% decrease in antifibrinogen antibody binding, but also an inability of EDTA or excess exogenous fibrinogen to dissociate more than half of platelet-associated fibrinogen, as well as the progressive association of bound fibrinogen with the platelet cytoskeleton. Costimulation of platelets with ZnCl2 and thrombin or ZnCl2 and ADP enhanced overall fibrinogen binding but not the EDTA-resistant component, and prevented the recovery of irreversibly bound fibrinogen with the Triton X-100 insoluble cytoskeleton. Costimulation of PMA- or Zn(2+)-treated platelets with low doses of A23187, however, restored the stabilization of platelet-fibrinogen interactions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440504 TI - On the significance of different aequorin loading techniques on intracellular aequorin discharge, baseline calcium, platelet aggregation and aequorin-indicated Ca(2+)-transients. AB - The study compares the decay of intracellular luminescence activity (Lmax), the levels of basal [Ca2+]i in resting platelets, and agonist-induced peak [Ca2+]i signals in platelets loaded with aequorin using the EGTA-, DMSO- and hypoosmotic shock treatment (HOST)-techniques. The highest load of intracellular aequorin with almost unchanged luminescence activity during 4 h was achieved with HOST. Lmax decreased linearly in EGTA- and HOST-platelets, but the decay rate and the levels of basal [Ca2+]i were significantly lower in HOST-platelets. Platelet aggregation and aequorin-indicated [Ca2+]i-rise induced by thrombin and collagen were similar in EGTA- and HOST-platelets. In HOST-platelets, ADP-induced platelet aggregation was always accompanied by aequorin-signals, while at a similar time point, aequorin-signals were absent in 3 of 5 cases in EGTA-platelets. The initial aequorin loading was highest in DMSO-platelets, but Lmax described an exponential decay, which was most pronounced when DMSO-platelets were maintained in Ca(2+)-free buffer (R2 = 0.86). Agonist-induced platelet aggregation was significantly reduced in DMSO-platelets: thrombin-stimulation was accompanied by a significantly lower and delayed [Ca2+]i-rise and no aequorin-signal was obtained in response to ADP in 3 of 5 cases. The study shows that in addition of being a rapid loading-technique, the criteria of high intracellular aequorin load with low luminescence consumption, low basal [Ca2+]i and completely preserved platelet functions are most convincingly met by the HOST-method. PMID- 1440505 TI - Low molecular weight fibrinogen degradation products stimulate the release of growth factors from endothelial cells. AB - Cultured porcine aortic endothelial cells (PAEC) constitutively produce and secrete in their culture medium mitogens collectively called endothelial cell derived growth factors (EDGFs). Incubation of PAEC with fibrinogen-degradation products (FDPs) obtained by plasmin digestion of highly purified fibrinogen caused an increased release of EDGFs, as assessed by [3H]-thymidine incorporation in 3T3 mouse fibroblasts. The effect was time-dependent and correlated with the degree of fibrinogenolysis. It was accompanied by elongation of the cells. Neither increase in EDGFs release nor cell damage was observed when non-degraded fibrinogen was incubated with endothelial cells. Low molecular weight fibrinogen degradation products (LMWFDPs) (M(r) less than or equal to 10,000), and the higher molecular weight fibrinogen fragments D and E were tested under the same conditions. Only the LMWFDPs caused elongation and damage to PAEC and a marked stimulation (up to 12 fold) of EDGFs release. A low density growth assay revealed that the released EDGFs were mitogenically active on the same PAEC. The activity of the released EDGFs was time and dose dependent on both 3T3 fibroblasts and PAEC, indicating that LMWFDPs caused enhanced release of EDGFs that can act in paracrine and autocrine fashion. This study suggests an additional role for fibrinogenolysis contributing to wound healing, and possibly to atherosclerosis. PMID- 1440506 TI - Acquired protein S deficiency might be associated with a prethrombotic state during estrogen treatment for tall stature. PMID- 1440507 TI - Lack of an acute effect of Pb2+ on platelet aggregation. PMID- 1440508 TI - Pregnancy and the bleeding time. PMID- 1440509 TI - The de-endothelialized rat carotid arterial graft: a versatile experimental model for the investigation of arterial thrombosis. AB - A novel model of arterial thrombosis was developed. A mechanical endothelium denuding injury was created (using a scalpel blade) on harvested, freezer-stored rat carotid arteries. Vessel length of 5 mm. were grafted into the femoral arteries of recipient Sprague-Dawley rats using microvascular anastomotic technique. Patency rates in untreated animals were compared with those in animals receiving systemic aspirin or heparin. The control group patency after 2 hours of flow was 15%, while grafts in aspirin- and heparin-treated animals achieved 35% and 95% patency rates, respectively. Uninjured non-frozen carotid grafts in untreated animals yielded a 95% patency rate, while frozen grafts achieved an 80% patency. Therapeutic levels of aspirin, heparin, and urokinase were confirmed through tail bleeding and whole blood clotting tests, as well as platelet aggregation studies and scanning electron microscopy of the graft lumenal surfaces. A long-term series using syngeneic grafts placed in recipients (Lewis to-Lewis) and employing systemic heparinization demonstrated maintenance of patency for 4 weeks. Scanning electron microscopy revealed good re endothelialization, well advanced by one week. Histology confirmed the regrowth of endothelial cells, but showed sparse cellular repopulation of medial and adventitial layers. The mechanical injury model was compared to enzymatic de endothelialization (using trypsin or collagenase), for which patency rates were similar (10% and 0%, respectively). Trypsin de-endothelialized vessels were tested in vitro for the amount of active trypsin remaining bound to the lumenal surface; no detectable activity was found when trypsin inhibitor was applied following trypsin treatment. The versatility of allowing both in vitro evaluation and in vivo patency assessment demonstrates the uniqueness and value of this new model, offering an avenue toward more direct investigations of surface-mediated thrombotic processes. PMID- 1440510 TI - Sphingosine inhibits factor Xa-catalyzed prothrombin activation on the surface of cultured calf pulmonary artery endothelium perturbed by hydrogen peroxide. AB - The effects of hydrogen peroxide on factor Xa-catalyzed prothrombin activation on the surface of vascular endothelial cells, and the inhibitory effect of sphingosine on prothrombin activation were studied in cultured calf pulmonary artery endothelial cells (CPAEC). Hydrogen peroxide enhanced factor Xa-catalyzed prothrombin activation on the cell surface in a time and dose-dependent manner. Sphingosine, a potent inhibitor of protein kinase C and the extrinsic pathway of blood coagulation, showed a partial inhibition of prothrombin activation on the surface of CPAEC. When cells were perturbed by hydrogen peroxide, sphingosine inhibited prothrombin activation and displaced factor Xa bound to the cell surface. PMID- 1440511 TI - Effects of cyclooxygenase inhibitors on ex vivo cysteinyl-leukotriene production by whole human blood allowed to clot spontaneously. Comparison to stimulated blood. AB - In ex vivo experiments we have investigated the effects of single oral administrations of aspirin (100 or 1000 mg) or ibuprofen (200 or 1200 mg) on the formation of immunoreactive thromboxane (TX) B2 and cysteinyl-leukotrienes (LT) by whole human blood in vitro. Whole human blood was allowed to clot spontaneously and in addition, in the presence of the chemotactic tripeptide f Met-Leu-Phe (FMLP, 1 microM), or the non-physiological ionophore A 23187 (10 microM). Oral pretreatment with aspirin or ibuprofen led to dose-dependent inhibition of the TXB2 production in the presence of any of the stimuli used. After drug pretreatment the cysteinyl-LT production was not significantly enhanced in blood stimulated with FMLP or allowed to clot spontaneously as compared to values prior to oral drug administration. However, pronounced inhibition of the cyclooxygenase pathway was accompanied by an enhanced cysteinyl LT formation when ionophore A 23187 was used as a stimulus. This could also be shown in experiments where the cyclooxygenase inhibitors were added in vitro. The higher oral dose of aspirin reduced the ex vivo cysteinyl-LT production in spontaneously clotting blood. By reverse phase HPLC immunoreactive cysteinyl-LT were characterized as a mixture of LTD4 and LTE4 as well as small amounts of LTC4. The data show that in the presence of therapeutic cyclooxygenase inhibitors no enhanced formation of cysteinyl-LT occurs in human blood in vitro after physiological stimuli such as contact activation of the clotting cascade or FMLP. PMID- 1440512 TI - Changes of the fibrinolytic system in liver dysfunction: role of portal hypertension. AB - The contribution of hemodynamic changes to the pathogenesis of accelerated fibrinolysis in liver disease was investigated in rats. In animals with hepatic lesions induced by a 7-week inhalation of carbon tetrachloride there was a significant increase in blood t-PA activity and PAI activity, with no significant change in portal pressure. Following a 10-min portal vein occlusion there was a marked increase in portal pressure and t-PA activity and a significant decrease in PAI activity. Following ligation of both portal vein and hepatic artery, t-PA activity increased to a higher extent and PAI activity was reduced to a lesser extent than changes found in portal-stenosed rats. Our data suggest that high t PA circulating levels in liver disease could be related not only to the reduced t PA clearance as a consequence of liver injury but also to hemodynamic changes. PMID- 1440513 TI - Combined inherited protein S and heparin co-factor II deficiency in a patient with upper limb thrombosis: a family study. AB - A 42-year-old Italian woman presenting with spontaneous deep vein thrombosis of the right arm, was found to have inherited a deficiency of both protein S (PS) and heparin co-factor II (HC II). The two defects seemed to segregate independently, since her son exhibited only a HC II deficiency while one of her sisters manifested only the PS defect. All affected patients appeared heterozygous for one or other or both deficiency states. The proposita and her sister exhibited a congenital PS deficiency consisting of normal or near normal levels of total PS antigen and C4b-binding protein (C4b-BP) but a moderate reduction both of free PS antigen and of PS functional activity. In addition, the proposita and her son had half normal levels of HC II antigen and activity. Except for the proposita, all were asymptomatic. Inherited deficiencies either of PS or of HC II have been associated with thrombotic manifestations. Since the proposita had an inherited combined defect of the two proteins, severe thrombotic events might be expected. However, this was not found to be the case. The role of HC II deficiency in the pathogenesis of thrombosis whether alone or combined remains to be fully investigated. PMID- 1440514 TI - An animal model of fibrinolytic bleeding based on the rebleed phenomenon: application to a study of vulnerability of hemostatic plugs of different age. AB - The primary bleeding time is prolonged when tested during the infusion of both plasminogen activators and anticoagulants, and such sites frequently exhibit rebleeding after initial hemostatic control. This study describes an animal (rabbit) model which distinguishes fibrinolytic from anticoagulant hemorrhage and further applies the model to the study of hemostatic plugs of increasing age. In this model, rebleeding occurred from hemostatically-stable ear puncture sites induced prior to infusion of streptokinase (SK) or recombinant tissue-plasminogen activator (rt-PA), but not of heparin or hirudin. This distinction was apparent even for lesions induced only 15 minutes prior to the infusion and fibrinolytic bleeding was observed in such lesions induced up to 24 hours earlier. Post infusion sites bled more quickly than did pre-infusion sites, and there was a gradual decrease in susceptibility of such prior trauma sites for rebleeding, evidenced not only by a lower proportion of sites that rebled, but also by a longer lag time after starting SK or rt-PA before such rebleeding occurred. At the dosages tested, SK showed a trend (not statistically significant) toward more sites that rebled, while rt-PA showed a trend towards a longer duration of rebleeding. Thus, this animal model of rebleeding appears to be unique for fibrinolytic agents and allows for more detailed study of the physiological mechanisms of such bleeding and for a multifaceted comparison of the bleeding potential of plasminogen activators. PMID- 1440515 TI - Interaction of factor VIII with phospholipids: role of composition and negative charge. AB - Radiolabelled human anti-FVIII:C antibody was affinity-purified according to its ability to bind to factor VIII-phospholipid (FVIII-PL) complexes, yielding a fraction directed against the phospholipid binding-site (PL-site antibody). This antibody was used as a specific probe for FVIII binding to PL vesicles containing a variety of natural and synthetic PLs. Of purified PLs tested for FVIII binding, phosphatidyl serine (PS) and phosphatidic acid (PA) were highly active, phosphatidyl inositol (PI) much less so, and both phosphatidyl ethanolamine (PE) and phosphatidyl choline (PC) inactive: the apparent dissociation constant (Kd app) for FVIII binding to PS:PC vesicles showed a strong dependence on PS content. Free-flow electrophoresis of vesicles confirmed FVIII binding to PS:PC required both net negative charge and specific head-group: neither PS vesicles given a positive charge with stearylamine nor PC vesicles made negative with dicetyl phosphate bound FVIII. It is concluded that the negative charge required for FVIII binding must be presented on the phospholipid surface in the correct orientation: phosphatidyl serine supplies this charge in coagulant-active PL preparations. PMID- 1440516 TI - Effects of antithrombotic drug, Y-20811 on mural thrombus formation and intimal thickening following intimal injury. AB - Inhibitory effect of Y-20811 on platelet thrombus formation induced by mechanical intimal injury and subsequent intimal fibrous thickening was studied. In the short term experiment, polyethylene tubing was inserted into the rabbit aorta and was drawn out one hour after with or without Y-20811 administration, then the rabbits were sacrificed. In the experiment for the quantitative analysis of platelet adhesion, 51Cr-labeled platelets were used. Radioactivities of 2cm length of the injured segment of the thoracic aorta and the proximal 2cm of the normal segment were measured. Radioactivity of the injured segment was significantly lower in rabbits treated with Y-20811 than the control ones. The mean thickness (area of thrombi/length of injured intima) and the maximal thickness of the mural thrombi in the Y-20811-treated rabbits were significantly lower than those in control rabbits. De-endothelialized area showed raised platelet thrombi in the control group and diffuse thin-layered platelet sheets in Y-20811-treated rabbits. In the long term experiment, polyethylene tubing was indwelled for 24 hours. Rabbits were sacrificed 10 days after drawing out the tubing. Through the experiment Y-20811 was injected intravenously every 24 hours. There was no significant difference between the control group and the Y-20811 treated one in both mean thickness and maximal thickness of the intimal fibromuscular thickening. The experiments indicate that Y-20811 has an inhibitory effect on platelet thrombus formation following intimal injury, but subsequent myointimal thickening is not inhibited by the drug. PMID- 1440518 TI - Cathepsin G, a regulator of human vitamin K, dependent clotting factors and inhibitors. AB - Cathepsin G was used in vitro to digest human factor VII and factor IX. Clotting assays indicated that the proteinase affected a rapid loss in coagulant activity while in the presence of calcium ions the activity was almost totally protected. SDS-polyacrylamide gel electrophoresis indicated the removal of a peptide from each zymogen, VII-L from factor VII and IX-L from factor IX. This lead to the formation of VII-H and IX-H respectively. N-terminal analysis of the VII-H and IX H products and COOH-terminal analysis of the VII-L and IX-L products confirmed that cathepsin G had cleaved position Phe40:Trp41 in factor VII and factor IX. The cleavage site is the same as that when cathepsin G is reacted with factor II, factor X and protein C. The unique action of cathepsin G may be part of a regulatory system for controlling the coagulant activity of vitamin K dependent clotting in vivo. PMID- 1440517 TI - Congenital protein C deficiency and myocardial infarction:concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis. AB - A 29-year-old man with congenital protein C deficiency and acute myocardial infarction is reported. Four hours after the onset of chest pain, he was treated intravenously with tissue-type plasminogen activator. Subsequent coronary angiography revealed only slight stenosis of the left anterior descending coronary artery without any atherosclerosis. The propositus, his brother, and his mother, showed low levels of both protein C activity and antigen, while plasma thrombomodulin levels were normal. His grandfather had died from acute myocardial infarction at 38 years of age. We investigated several other risk factors for arterial thrombosis, including factor VII, fibrinogen, heparin cofactor II, lipoprotein (a), and anticardiolipin antibodies. No other haemostatic abnormalities apart from factor VII hyperactivity were detected in this family. To study the effects of protein C and factor VII on procoagulant activity, prothrombin time was measured after the addition of activated protein C and factor VII to protein C-deficient plasma. The prothrombin time ratio decreased along with an increase in the factor VII level. It also decreased with a decrease in the activated protein C level. These findings indicated that the procoagulant activity of factor VII was enhanced by low protein C levels, suggesting that concomitant factor VII hyperactivity may cause acute myocardial infarction in patients with protein C deficiency. PMID- 1440519 TI - Endogenous heparinase-sensitive anticoagulant activity in human plasma. AB - In this paper we show that an anticoagulant activity, which we measure by thrombin time, appears in human plasma after its exhaustive proteolytic digestion. This activity is extremely heat stable, it is resistant to chondroitin ABC lyase (E.C.4.2.2.4) and heparan sulfate lyase (E.C.4.2.2.8), it is sensitive to heparin lyase (E.C.4.2.2.7) and to nitrous acid treatment: we suggest that it can be identified as authentic heparin. The amount present in 1 ml of plasma of healthy subjects corresponds to 0.1-0.2 I.U. of standard heparin (150 I.U./mg). Proteolytically digested human plasma was submitted to ion-exchange chromatography on DEAE-Sephacel and the anticoagulant activity in the fractions eluted at the different molarities of NaCl was measured by thrombin time. This analysis shows that the anticoagulant activity elutes at very low ionic strength. The possibility that interactions of the endogenous heparin with proteins or protein fragments are responsible for the difficulty in isolating heparin from human plasma is discussed. PMID- 1440520 TI - Endoglycosidase H digestion of Yukb (Pena) alloantigen. AB - We characterized a platelet specific alloantigen (Yukb). In immunoblotting, anti Yukb antibody was found to react with both 110 kDa and 96 kDa bands under nonreducing condition. Immunoblotting followed by separation by two-dimensional electrophoresis (isoelectric focusing/SDS-PAGE) showed that the 96 kDa band had a pI of 5.1-5.8, while the 110 kDa band had a pI of 5.2-5.7. The 96 kDa band was identified as glycoprotein (GP) IIIa on the basis of periodic acid Schiff staining, but the 110 kDa band was not characterized. These results implied that it is difficult to determine differences in antigenic epitopes between Yukb and PlA1 antigens by the electrophoresis. Yukb antigen, unlike PlA1 antigen, was partially destroyed by chymotrypsin treatment. Furthermore, endoglycosidase H digestion resulted in loss of the Yukb epitope, while the PlA1 determinant was retained on the three bands with lower molecular weights after endoglycosidase H digestion. The transfer of Yukb antigens recognized by anti-Yukb antibody into the supernatant of platelets treated with endoglycosidase H was also found using mixed passive hemagglutination test. The results indicated that the Yukb epitope might be located to the endoglycosidase H digested N-linked high mannose carbohydrate chains of GP IIIa or hybrid type chains of GP IIIa, which is different from the location of PlA1 epitope. PMID- 1440521 TI - Antithrombin III, C1 inhibitor, methylglyoxal, and polymorphonuclear leukocytes in the development of vascular complications in diabetes mellitus. AB - Under conditions closely approximating those in vivo (100 mM sodium carbonate pH 7.3 with 0.9% NaCl, 37 degrees C), antithrombin III (AT III) and the C1 inhibitor (C1-INH) are inactivated by methylglyoxal (MG) with pseudofirst-order kinetics and second-order rate constants of 25.2 and 7.8 M-1 min-1, respectively. A study of the functional status of neutrophils from patients with diabetes mellitus (DM) prompts an idea that under hyperglycemia in the diabetic organism the polymorphonuclear leukocytes (PML) endure 'arousal' that is identical or analogous to their activation. Indeed, nonstimulated PML from DM patients display (i) an almost sixfold higher luminol-dependent chemiluminescence and (ii) a double rate of oxygen uptake as compared with those from healthy donors, and (iii) are capable of MG formation in the presence of acetoacetate, which in vivo may be an additional source of this inactivator of AT III and C1-INH in diabetic patients. Conditions leading to ketosis or lactic acidosis are discussed, and a probable scenario is proposed for the organismic deterioration in DM. PMID- 1440522 TI - Pharmacological profile of a native dermatan sulfate. AB - We performed different "in vivo" investigations to study the pharmacological properties of a native DS: anti-thrombosis by the stasis model, bleeding potential by tail transection bleeding time and template bleeding time, and profibrinolysis by a growing thrombus model and by an established thrombus model. The results suggest that DS is a safe antithrombotic drug by i.v. administration without bleeding potential, even at very high doses (up to 16 mg/Kg). DS has shown a protective index of at least 4 in contrast to heparin that has shown a protective index of 1. The profibrinolytic models so far studied did not evidence a clear profibrinolytic contribution to the antithrombotic properties of DS, but showed a prolonged antithrombotic action that cannot be explained only by the heparin cofactor II potentiation. PMID- 1440523 TI - Evaluation of plasma D-dimer in the diagnosis and in the course of fibrinolytic therapy of deep vein thrombosis and pulmonary embolism. AB - Blood samples were obtained from patients with deep venous thrombosis (DVT) or pulmonary embolism (PE) after angiographic confirmation as well as during fibrinolytic therapy with streptokinase. Plasma cross-linked fibrin degradation products were measured by a quantitative enzyme-linked immunoassay that recognizes the D-Dimer epitope. 24 patients with PE showed elevated D-Dimer levels (median; 25%-, 75%-quartile) (3,250 ng/ml; 1,270 ng/ml, 6,940 ng/ml) as well as 38 patients presenting with DVT (2,330 ng/ml; 1,760 ng/ml, 3,980 ng/ml). The sensitivity for the diagnosis of PE was 92%, for diagnosis of DVT 89% resp. 100%, depending on the cut-off limit. The D-Dimer level showed a correlation (r = 0.64) to the angiographically documented severity of PE quantified by the Miller's score, in contrast to DVT, where no such correlation could be found. During fibrinolytic therapy median levels rose from 3,020 ng/ml to 63,000 ng/ml within 8 hours and then fell within 6 days to 2,930 ng/ml. 10 patients with PE showed a good correlation (r = 0.72) between the reduction of Miller's score within 72 hours and D-Dimer 24 hours after the onset of therapy. In 17 patients with fibrinolytic treatment of DVT no correlation between D-Dimer and clot lysis could be found. These findings indicate that D-Dimer can provide additional information in the diagnostic procedure of suspected PE. During fibrinolytic therapy of PE with streptokinase, D-Dimer could serve as an early prognostic parameter of successful thrombolysis. PMID- 1440524 TI - Comparative studies in vitro and ex vivo on the anticoagulant effect of a reversible and an irreversible tripeptide inhibitor of thrombin. AB - Comparative studies on the anticoagulant effect of D-Phe-Pro-Arg-H (ALD) and D Phe-Pro-Arg-CH2Cl (CMK) were carried out in order to estimate whether the reversible or the irreversible tripeptide inhibitor of thrombin would be more suitable to develop as a novel anticoagulant. Conventional screening assay methods in vitro were focused on the functional stability of the compounds in whole blood and blood components while ex vivo the changes in whole blood clotting time under parenteral application of the inhibitors were investigated. The efficacy of ALD relative to that of CMK was found to depend on the complexity of the test systems. Thus CMK was the more inhibitory in citrated plasma, but ALD showed the higher potency in whole blood. When incubated in various systems such as human whole blood, serum, solutions of isolated plasma proteins, digestive juices and tissue homogenates, respectively, the inhibitory activity of ALD showed only slight decreases for several hours while marked or substantial loss of activity was observed with CMK under identical conditions. ALD administered parenterally to rabbits proved to be powerful anticoagulant; CMK exhibited only a weak and transient anticoagulant effect presumably due to its ability to bind irreversibly to various plasma and tissue proteins. Accordingly, the reversible inhibitor ALD should be more suitable to develop as an anti-coagulant than CMK, its irreversibly acting analogue. PMID- 1440525 TI - Recombinant human factor VIIa (rFVIIa) in a rabbit stasis model. AB - The thrombogenicity of recombinant human FVIIa (rFVIIa) and FEIBA was studied in a rabbit stasis model. Only minor thrombus formation in isolated vein segments during 10 min. of stasis was seen following the administration of rFVIIa 100-1000 micrograms/kg or FEIBA 50-100 U/kg whereas both compounds caused clear thrombus formation during 30 min. of stasis. RFVIIa caused no change in platelet counts or plasma fibrinogen 3 hours after administration, whereas a small decrease of APTT was seen due to the direct effect of rFVIIa in this assay. In contrast, FEIBA caused a significant and dose-dependent decrease of platelet counts as well as of fibrinogen, and an increase of APTT which demonstrate a general consumption of coagulation factors. In conclusion the study demonstrated a local pharmacological effect of rFVIIa in the absence of a general activation of the coagulation cascade. PMID- 1440526 TI - Stimulation of PAF-synthesis in pulmonary artery endothelial cells by Staphylococcus aureus alpha-toxin. AB - Staphylococcus aureus alpha-toxin is a pore-forming exotoxin that probably represents a significant virulence factor in staphylococcal infections. Previous studies demonstrated that this agent stimulated arachidonate metabolism with subsequent formation of prostacyclin in endothelial cells and leukotriene B4 in granulocytes. We now examined the effect of alpha-toxin on the synthesis of platelet-activating factor (PAF) in cultured porcine pulmonary artery endothelial cells. PAF was labeled by bioincorporation of tritiated acetate and separated/quantitated using thin-layer chromatography, straight-phase-HPLC, or post-HPLC-bioassay. Alpha-toxin induced synthesis of small amounts of PAF in a time- and dose-dependent manner. The maximal amount of PAF elicited by alpha toxin was approximately 7% of that observed after application of the ionophore A23187. Staphylococcal alpha-toxin but not the ionophore induced a rapid fall in cellular ATP-content. On kinetic grounds, the decrease in ATP-levels did not explain the differences in stimulated PAF-synthesis. Low amounts of PAF induced by the action of alpha-toxin on endothelial cells may contribute to the development of inflammatory lesions in infectious disease. PMID- 1440527 TI - Heparin enhances platelet aggregation irrespective of anticoagulation with citrate or with hirudin. AB - The effects of anticoagulation with citrate or hirudin on heparin effects on platelet aggregation was studied with whole blood aggregometry on blood from healthy volunteers. Platelet aggregation was initiated by collagen. The heparin effect was also studied with filtragometry where hirudin was used as the anticoagulant. In citrated blood, a mean collagen dose of 0.42 +/- 0.04 micrograms/ml resulted in an impedance change of 1.1 +/- 0.3 Ohm. Preincubation with heparin doses of 0.5, 2.5 and 5 IU/ml enhanced the impedance induced by the same dose of collagen by 2.9 +/- 1.4, 11.4 +/- 1.6 and 9.9 +/- 2.3 times, respectively (p less than 0.0001, ANOVA). In hirudinized blood a similar degree of change in impedance (1.5 +/- 0.2 Ohm) was achieved at significantly lower concentration of collagen (0.08 +/- 0.006 micrograms/ml, p less than 0.0001). Preincubation with heparin in doses of 0.5, 2.5 and 5 IU/ml increased impedance by 1.5 +/- 0.5, 3.9 +/- 1.6 and 1.3 +/- 0.5 times, respectively (p less than 0.0001, ANOVA). The dose-related increments were smaller in hirudinized blood as compared to citrated blood (p less than 0.04). With filtragometry, heparin dose dependently shortened the aggregation time (p less than 0.0007). Compared to hirudin alone as anticoagulant, heparin in an equipotent dose in these experiments shortened aggregation time (p less than 0.05). In conclusion, heparin enhanced platelet aggregation both in calcium-chelated blood and in blood anticoagulated with hirudin. Heparin also dose-dependently increased platelet aggregation in filtragometry. Thus the heparin potentiating effect on platelet aggregation seems to be independent of extracellular ionized calcium and be operative at physiological calcium concentrations. PMID- 1440528 TI - Post-operative pulmonary embolism and meta-analysis. PMID- 1440529 TI - Does fibrinogen contain populations with different degree of sialylation? AB - The reactivity of the galactose specific lectin from Ricinus communis seeds, ricin, towards the fractions of fibrinogen separated by DEAE-cellulose chromatography and their isolated glycopeptides was studied. Ricin is known to differentiate oligosaccharide chains with different degree of sialylation. The results indicated that the fractionation of fibrinogen is not correlated with a different degree of sialylation of its oligosaccharide chains. The higher sialic acid content of the most acidic fraction correlates with a higher neutral sugar content due to the presence of highly glycosylated contaminants. The possibility that the heterogeneity in the degree of sialylation is only of intramolecular nature is discussed. PMID- 1440530 TI - Coagulation and fibrinolytic system impairment in insulin dependent diabetes mellitus. AB - Selected coagulation and fibrinolytic parameters were assessed in 40 insulin dependent diabetes mellitus patients with varying degrees of metabolic control; 30 healthy subjects matched for age and sex formed the control group. Activated Partial Thromboplastin Time, Prothrombin Time, Fibrinogen, Factor VII, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, Plasminogen Activator Inhibitor-1, tissue-Plasminogen Activator were functionally evaluated. Antigenic levels of tissue-Plasminogen Activator, Thrombin-Antithrombin complexes and fibrinolytic specific product B beta 15-42 were also determined. Compared to the control group diabetic patients displayed significantly higher levels of Fibrinogen (p < 0.01), Factor VII (p < 0.01), Thrombin-Antithrombin complexes (p < 0.01) and Plasminogen Activator Inhibitor-1 activity (p < 0.01). Regardless of the normal level of the tissue-Plasminogen Activator-related antigen, diabetic patients had tissue-Plasminogen Activator activity lower than the control group (p < 0.05). Coagulation Factor VII and Thrombin-Antithrombin complexes were increased only in the patients with poor metabolic control (p < 0.01). Activated Partial Thromboplastin Time, Prothrombin Time, Antithrombin III, Protein C, Plasminogen, alpha 2-Plasmin Inhibitor, B beta 15-42 fibrin peptide were found to be in the normal range. Fibrinogen correlated positively with fasting blood glucose (p < 0.05) and Thrombin-Antithrombin complexes with glycosylated haemoglobin (p < 0.05), whereas Factor VII was positively correlated with glycemia (p < 0.01) and glycosylated haemoglobin (p < 0.05). Higher levels of Fibrinogen were found in patients affected by nephropathy (p < 0.005) or neuropathy (p < 0.05). These results demonstrate an impairment of the haemostatic balance in diabetic patients, that is a possible hypercoagulable state, which represents an important factor in the pathogenesis of atherosclerotic complications. PMID- 1440531 TI - Reduced functions of intracellular Ca2+ in aggregation, secretion and protein phosphorylation of permeabilized platelets from stroke-prone spontaneously hypertensive rats. AB - Aggregation, secretion and 47kDa protein (P47) phosphorylation by various agonists such as thrombin, ADP and ionophore A23187 were markedly reduced in platelets from stroke-prone spontaneously hypertensive rats (SHRSP) compared with those of age-matched Wistar Kyoto rat (WKY) platelets, suggesting defective functions of intracellular Ca2+ in SHRSP platelets (Tomita et al. Hypertension 1989; 14: 304-315). To clarify the mechanism of the platelet hypofunctions, saponin permeabilized platelets were prepared to compare the responses of platelets from both rats in varying concentrations of extracellular Ca2+. The leakage of lactate dehydrogenase from saponin (15 micrograms/ml)-treated platelets was approx. 5% of total activity; the degree of the leakage in both platelets did not differ. In saponin-treated platelets, extracellular Ca2+ alone did not induce either aggregation or secretion in both strains. However, in the presence of 1-oleoyl-2-acetylglycerol (10 micrograms/ml), Ca2+ dose dependently stimulated both aggregation and secretion. Under this condition, Ca2+ sensitivity of aggregation, secretion and P47 phosphorylation in SHRSP platelets were significantly reduced compared with those in WKY platelets. These results strongly suggest that intracellular Ca2+ functions are impaired in SHRSP platelets. PMID- 1440532 TI - Reduction of the anticoagulant activity of glycosaminoglycans on the surface of the vascular endothelium by endotoxin and neutrophils: evaluation by an amidolytic assay. AB - The processes that underlie the coagulopathy observed in severe infection are not fully understood, but seem to be due to an imbalance in the antithrombotic, and prothrombotic properties of the vascular endothelium. Sulphated glycosaminoglycans (GAGs) present on the vessel wall represent an important component of the non-thrombogenic nature of the endothelium. We have modified an amidolytic assay to study the functional ability of GAGs on human umbilical vein endothelial cells (HUVECS), and investigate the effect of E. coli endotoxin and neutrophils on HUVEC surface anticoagulant activity (SAA). Neither endotoxin alone, nor separated neutrophils at lower concentrations (less than 10(6) neutrophils per ml), had major effects on endothelial SAA. When activated neutrophils were incubated with HUVECS pre-stimulated with endotoxin, a significant decrease in SAA was seen using either plasma (mean percentage of control 67.8% +/- sem 7.8; p < 0.02) or purified ATIII (mean percentage of control 69% +/- sem 4.6; p < 0.001). We suggest that alterations in endothelial surface GAGs may occur during sepsis and inflammation, and that this may have important consequences for vascular function. This system will allow the further study of the role of GAGs in the intravascular thrombosis of severe sepsis, and other inflammatory diseases. PMID- 1440533 TI - Purification of rabbit, rat and mouse protein C with the use of monoclonal antibody to human protein C, PC01. AB - Ca(++)-dependent monoclonal antibody specific to gamma-carboxyglutamic acid (Gla) domain of protein C was produced. It did not cross-react to the other vitamin K dependent plasma proteins but to protein C of the other species. Using this monoclonal antibody, PC01, rabbit (170 micrograms), rat (60 micrograms) and mouse (40 micrograms) protein Cs were isolated from 100 ml of their plasma by affinity chromatography. All of these protein Cs were two chain form linked by disulfide bond as well as human protein C and activated by thrombin-thrombomodulin complex. Rat and mouse protein Cs showed similar characters to human protein C. On the other hand rabbit protein C had different M(r) of heavy and light chains and showed lower anticoagulant activity compared with human protein C. PMID- 1440534 TI - Evidence for the role of dialysis hypoxemia in the pathogenesis of hemodialysis induced rise in tissue-type plasminogen activator. AB - It is well known that hemodialysis (HD) causes a rise in plasma tissue-type plasminogen activator (t-PA). Although there have been several suggested mechanisms responsible for this effect of HD, the precise cause has not been well understood yet. Another complication of HD, when performed with acetate containing dialysate, is hypoxemia, which is commonly observed during the first hour of the session. The purpose of this study was to investigate the relationship between dialysis hypoxemia and HD-induced t-PA changes during the first two hours of HD. HD caused significant increase in plasma t-PA antigen levels. When individual t-PA profiles versus time were examined, two patterns were observed. Whilst ten subjects (%56) experienced minimal or no increase, t-PA antigen level of the remaining eight subjects began to rise at 30 minutes and continued at that level up to 90 minutes, when the last samples were drawn. The courses of pO2 were also different; whilst the former group had "early-onset and short-term" hypoxemia, the latter had "late-onset and prolonged" hypoxemia. The amount of increase in t-PA antigen and the amount of decrease in pO2 were correlated at 60 and 90 minutes of the HD session. Thus, it is concluded that dialysis hypoxemia may contribute to HD-induced rise in plasma t-PA levels. Further studies comparing different dialysates and dialyser membranes are required to confirm this hypothesis. PMID- 1440535 TI - Inhibitory effect of activated protein C on platelet aggregation induced by the prothrombin-converting reaction. AB - The present study was undertaken to elucidate the effect on platelet aggregation of the prothrombin-converting reaction on platelets with or without activated protein C (APC). A reaction mixture of washed platelets from human individuals, Factor Xa and prothrombin markedly induced platelet aggregation; maximum aggregation rates, 31.3-92.5%, and times to reach to maximum aggregation, 11.6 to 20.1 min. This aggregation was inhibited by the addition of APC with 50% inhibition concentration (IC50) value of 14.4 U/ml. APC also inhibited thrombin generation in the reaction mixture in a dose-dependent manner with IC50 value of 0.96 U/ml. However, APC did not inhibit the thrombin (0.1 CU/ml)-induced platelet aggregation at concentrations of up to 30 U/ml. These findings suggest that APC has no direct inhibitory effect on platelet aggregation and that APC inhibits platelet aggregation through inhibition of thrombin generation. PMID- 1440536 TI - Interactions between thrombolytic agents and platelets: effects of plasmin on platelet glycoproteins Ib and IIb/IIIa. AB - The mechanisms by which thrombolytic agents affect platelet function are not yet elucidated. The aim of the present study was to investigate the effects of plasmin, generated by thrombolytic agents in plasma, on platelet glycoproteins (GP) Ib and IIb/IIIa. Platelet-rich plasma was incubated with pharmacological amounts of streptokinase, anistreplase and tissue-type plasminogen activator and the platelet surface GP's were investigated with a panel of monoclonal antibodies using flow cytometry. As assessed from the mean fluorescence intensity of incubated and control platelets, no significant changes in the binding of antibodies to GP Ib and GP IIb/IIIa were found. The functional integrity of these glycoproteins was severely impaired by treatment with the thrombolytic agents, as shown by significant inhibition of ADP- and ristocetin-induced platelet aggregation. Experiments with purified plasmin and washed platelets indicated significant degradation of GP IIb/IIIa and upregulation of GP Ib, which is in agreement with previous findings. In addition, platelet activation by plasmin was shown using two monoclonal antibodies to activation-specific antigens. We conclude that degradation of platelet GP's by plasmin offers no likely explanation for the defect in platelet function, which is induced by thrombolytic agents in platelet-rich plasma. PMID- 1440537 TI - Inhibition of plasma kallikrein. Kininase and kinin-like activities of preparations from the medicinal leeches. AB - The medicinal leech salivary gland secretion deprived of hirudin antithrombin activity inhibits amidolytic (substrate S-2302) and kininogenase (substrate kininogen) activities of plasma kallikrein, the main component of the intrinsic mechanism of blood coagulation. It therefore possesses high anticoagulant properties. Kininase (substrate bradykinin) activity of leech saliva and extracts from the medicinal leeches, as well as kinin-like effects of extracts heated at 100 degrees C have been detected. The last one is correlated with the hyperalgetic property of the heated extract. An analgetic effect was observed with the unheated extract but not with leech saliva after intranasal administration to rats. PMID- 1440538 TI - [Discovering and supervision in relation to veterinary environmental hygiene]. PMID- 1440539 TI - [Coordination in veterinary environmental problems]. PMID- 1440540 TI - [Education in veterinary environmental health]. PMID- 1440541 TI - [The quality of foodstuff of animal origin in relation to environmental pollution (government viewpoint)]. PMID- 1440542 TI - [Quality of foodstuff of animal origin in relation to environmental pollution]. PMID- 1440543 TI - [Neospora abortion in cattle in The Netherlands]. AB - Three cases of bovine protozoal abortion at three different dairy farms are reported. Multiple abortions had occurred, on two farms, and a sporadic abortion on the third farm. Histopathological examination of foetal tissues revealed a distinctive multifocal necrotising encephalitis as well as focal inflammatory lesions in the myocardium, liver, kidney and lung. In one foetus protozoal tissue cysts were found in the brain and individual and clustered tachyzoites were seen in brain, and lung. In another foetus a cluster of tachyzoites was seen in a section of a placentoma. Immunohistochemically, tissue cysts as well as tachyzoites reacted with Neospora caninum antiserum. Tachyzoites were also detected in the brain lesions of the other two foetuses. The preliminary results of a histopathological survey of aborted bovine foetuses indicate that this protozoal infection may be an important cause of bovine abortion in The Netherlands. PMID- 1440544 TI - [Vesicular swine disease in The Netherlands]. AB - The clinical signs, diagnosis and epizootiology of swine vesicular disease (SVD) are described. The clinical appearance is illustrated by photographs of experimentally and naturally infected pigs. Special attention is paid to differences between SVD and foot-and-mouth disease (FMD) and to the choice of disinfectants. PMID- 1440545 TI - [The effect of feeding mangel-wurzels on blood beta-hydroxybutyrate level of milk producing cows]. AB - The effect of feeding dairy cattle mangel-wurzels on the serum increased concentration of beta-hydroxybutyrate was investigated in serum is normally indicative of an increased catabolism of fats in the liver as a result of an energy shortage. Feeding cattle large amounts of mangel-wurzels can cause the serum beta-hydroxybutyrate concentration to increase above normal reference values, thus seemingly indicating that there is a (sub)clinical acetonaemia. In fact the increased concentration of beta-hydroxybutyrate is probably the result of an increased production of butyrate in the rumen. PMID- 1440546 TI - [Rickets-like bone changes in goat kids fed with artificial milk intended for calves]. AB - In a large commercial goat farm rickets-like symptoms were diagnosed in goat kids. The disease was probably caused by the synthetic milk which was freely available to the kids. The milk feed was for calves and had a calcium-phosphorus ratio of 0.83:1. PMID- 1440547 TI - [Carpal ligament lesions: a underrated problem in dogs]. AB - Traumatic hyperextension of the carpus in the dog may result in severe lesions of the palmar ligaments, which cannot be treated by coaptation splinting alone. Treatment in three dogs by partial arthrodesis using plate osteosynthesis is discussed. PMID- 1440548 TI - [Prevention of pseudo-fowl plague in other than commercially bred poultry]. PMID- 1440549 TI - [Annual cocktail-vaccination for dogs and cats]. PMID- 1440550 TI - [Sunlight dermatitis]. PMID- 1440551 TI - [Premature infants and hepatitis B vaccination. Study Group Prevention Neonatal Hepatitis B]. AB - Since 1986 health authorities in the Netherlands advise to vaccinate preterm infants at similar age as term infants, without correction for their shortened gestational age. This advice was based on a study, which showed comparable immune responses after DTP vaccination in preterm and term infants. To assess the immunogenicity of hepatitis B vaccination not corrected for gestational age in preterm infants, we compared the antiHBs titer after hepatitis B vaccination in 44 preterm infants with the antiHBs titer in 829 term infants. More than 95% of the preterm infants developed an adequate immune response (> 10 IU/l antiHBs), irrespective the vaccination scheme which varied in vaccine dose, the number of vaccinations and the onset of the first vaccination. The percentage preterm infants with an antiHBs titer > 10 IU/l (98%) was not different of the corresponding percentage of term infants (98%). Similarly, no difference between preterm and term infants was observed when an antiHBs value of 100 IU/l was considered a positive response, neither when active immunisation started at month 0 or month 3. The geometric mean titre at 12 months of age was considered. PMID- 1440552 TI - [Intracranial germinoma in children]. AB - Two cases of intracranial germinoma with different clinical expression, are described. The clinical symptomatology, the diagnosis and the treatment of this tumor are discussed. The symptoms depend on the localization of the tumor: in the suprasellar germinoma endocrinologic manifestations prevail while the symptoms in germinomas which are located in the pineal region, are mainly due to increased intracranial pressure. The diagnosis is suggested by the findings on CT-scan and MRI of the brain, but for the definitive diagnosis, pathologic examination of the tumor remains necessary. Blood HCG and alpha-fetoprotein are useful markers for follow-up; the value of angiotensin converting enzyme (ACE) as a marker, is still unclear. The ideal treatment of germinoma consists of surgical removal, postoperative chemotherapy and, afterwards, local radiotherapy. On the whole, the prognosis of this tumor is good. PMID- 1440553 TI - [Independence within reach. Ergotherapy treatment of children with a congenital reduction defect]. AB - The occupational therapy department of the University Hospital of Leiden treats a relatively large number of children, born with a dysmelia of the forearm. This article has been written to give information about the possibilities to supply these children with a prosthesis, and how this effects their level of independence. A short description of occupational therapy and the working of a myoelectric prosthesis will be followed by a case-study of a boy with plural congenital reduction defects. He needs several prosthesis and aids to become (mainly) independent of the help from others. It will be described how aids are made and tested, and how the prosthesis is used. The case-study illustrates that the different demands and desires which are demanded from prosthesis and aids, are related to the age and developmental level of the child. PMID- 1440554 TI - [Tropical malaria and sickle-cell anemia: a tropical surprise]. AB - A case of a very sick 2.5-year-old, Ghanese boy with fever, who fell in coma in the emergency room, is described. He was diagnosed as having blackwater fever (BWF) on clinical grounds. He also had a sickle cell anaemia. A short review of BWF is given and we discuss possible causes of the anaemia in this case. The anaemia in sickle cell anaemia is described and it appears that malaria tropica can lead to a severe hemolytic sickle cell crises. We discuss the combination of sickle cell anaemia and malaria tropica. PMID- 1440555 TI - [Intraosseous infusions in children]. AB - Tibial intraosseous infusions can be invaluable in the management of the pediatric patient who is in cardiac arrest or severe shock when vascular access by the intravenous route is unattainable. Recently there has been renewed interest in this procedure. There is a small risk of complications. PMID- 1440556 TI - [The precious child. Observations at the century of the child]. PMID- 1440557 TI - [Quantitative and qualitative stock-taking of scientific research in pediatrics in The Netherlands (1986-1990)]. AB - All Dutch academic and non-academic pediatric training centres were requested to give a survey of all scientific publications produced from 1986 to 1990. The initiative came from the board of the Dutch Pediatric Association. During the observation period (1986-1990) the number of international publications with an external reference system was twice when compared with 1981-1985. The quality of the publications was similar. In at least four of the participating academic pediatric hospitals most publications came from the subspecialty area of metabolic diseases, oncology/hematology, immunology/infectious diseases, and cardiology, both during the first and the second observation period. From 1986 to 1990 the total number of theses in which a pediatrician was the main promoter or promoter in charge came to 84. PMID- 1440558 TI - Linkage disequilibrium between DPA1 and DPB1 alleles among Norwegian Caucasoids and Japanese. AB - Associations between alleles at the DPA1 and DPB1 loci were analyzed in 181 Norwegian caucasoids. Associations were observed between the DPA1*0201 and the DPB1*0101, *0901, *1001 and *1101 alleles. An association between DPA1*0201 and the DPB1*0901 allele was also observed among 23 healthy Japanese and 24 Japanese MS patients. In addition, it appeared that among Japanese the DPA1*0201 allele may be associated to the DPB1*0501. In conclusion, alleles at the DPA1 and DPB1 loci display different associations among Norwegian caucasoids and Japanese. PMID- 1440559 TI - HLA-DR,DQ nucleotide sequence polymorphisms in five Melanesian populations. AB - HLA-DRB1 nucleotide sequence polymorphisms have been examined in 304 Melanesians from the Papua New Guinean coast (Madang), islands (Rabaul) and highlands (Goroka), and from New Caledonia and Fiji. A total of 20 HLA-DRB1 alleles were detected by oligonucleotide hybridizations of exon 2 HLA-DRB1 polymerase chain reaction products, in a typing protocol designed to detect all 42 officially designated HLA-DRB1 alleles. DRB1*1502 and 1101 alleles were the most common alleles in coastal and island Melanesians, while DRB1*1501, 1502 and 1408 predominated in Papua New Guinean highlanders. Undefined mixed lymphocyte reaction determinants in earlier studies of Melanesians could be accounted for in the present study as DRB1*0410, 1407 and 1408 in Papua New Guinean highlanders and as DRB1*1104 and 1602 in coastal people. Nucleotide sequence polymorphisms at HLA-DQA1, -DQB1, -DRB3 and -DRB5 were also determined for estimating HLA-DR,DQ allelic disequilibrium relationships; unusual haplotypes in Melanesians included DBR1*1502, DRB5*0101 and DRB1*0410, DQB1*0402. Previous claims of limited heterogeneity in the HLA-DR allele repertoire in Melanesians are now seen to reflect limitations of early typing reagents rather than any dramatic restriction in HLA-DR allelic diversity. PMID- 1440560 TI - Rapid identification of HLA-DRw53-positive samples by a generic DRB-PCR amplification without further analysis. PMID- 1440561 TI - HLA-DPB1 alleles and autoantibody subsets in systemic lupus erythematosus, Sjogren's syndrome and progressive systemic sclerosis: a question of disease relevance. PMID- 1440562 TI - Two novel HLA-DQB1*06 alleles reveal additional heterogeneity of HLA-DQw1. PMID- 1440563 TI - DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA. AB - The HLA class II genotypes were determined in the B-lymphoblastoid cell lines selected for the Tenth International Histocompatibility Workshop. The HLA class II genes were determined by the PCR-SSOP method using the reagents provided by the Eleventh Histocompatibility Workshop. Additional studies have been performed for further characterization of HLA class II polymorphism on these cell lines. It is observed that several cell lines have HLA class II haplotypes with the same DRB1, DQA1 and DQB1 alleles on both haplotypes but different alleles at the other class II loci, confirming that these cell lines are not truly HLA class II homozygous. Other cell lines carried HLA class II haplotypes which were only different at the DRB1 gene. These results suggest double recombination events or gene conversion-like events in generation of HLA DR, DQ haplotypes. These cell lines provide an important tool as references for HLA DNA typing. PMID- 1440564 TI - A serologically defined HLA-A11 split antigen. PMID- 1440565 TI - Adult onset spinocerebellar ataxia linked to HLA in a South African kindred of mixed ancestry. AB - Hereditary spinocerebellar ataxia (SCA) is a relatively common disorder in the Western Cape region of South Africa. At present there are no genetic markers available for prenatal or presymptomatic diagnosis. A large kindred of mixed ancestry with late onset SCA was studied in which the disorder segregated in an autosomal dominant fashion. HLA typing was undertaken on 44 family members, and the HLA haplotypes were assigned on the basis of segregation. The LIPED computer program, with a correction factor allowing for the age of onset, was used to analyze the pedigree for linkage to HLA. Of 22 individuals in whom disease status could be definitely assessed, only one recombinant between HLA and the SCA locus occurred. The lod score reached a maximum of 4.13 at a recombination fraction of 0.05, indicating the odds to be approximately 13,500 to 1 in favor of linkage between HLA and the putative disease allele for SCA. A possible recombination within the HLA region suggested that the disease allele lies telomeric of the HLA region. In view of the recent demonstration of tight linkage between SCA1 and D6S89, however, HLA should not be used for presymptomatic diagnosis or genetic counselling. PMID- 1440566 TI - Do human leukocyte antigens have a role to play in differential manifestation of multibacillary leprosy: a study on multibacillary leprosy patients from north India. AB - 118 multibacillary leprosy patients with differential manifestations were studied for the antigens they expressed at MHC loci to investigate the role of human leukocyte antigens in the differential response to the same causative agent. While the lepromatous leprosy (LL) patients showed a significant increase of Bw60, DR2, DRw8 and DQw1, borderline lepromatous (BL) patients had Bw52, DR9 and DQw7 significantly more often as compared to the normal controls. A comparison of LL, BL and mid-borderline (BB) patients showed a significantly higher frequency of Bw60 in LL patients as compared to the BL. However, Bw52, Bw53, DR9 and DQw7 were found significantly more often in the BL patients as compared to the LL patients but the difference failed to reach significance after pc. A comparison of HLA antigens in BB patients with those of either the LL or BL patients did not show any significant differences. PMID- 1440567 TI - Distribution of HLA class II alleles among Scandinavian patients with systemic lupus erythematosus (SLE): an increased risk of SLE among non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes? AB - HLA-DRB1, -DRB3, -DQA1 and -DQB1 alleles were determined by DNA typing in 51 Scandinavian patients with systemic lupus erythematosus (SLE) and 129 controls. DRB1*03,DRB3*0101,DQA1*0501,DQB1*0201 were significantly increased in the patient group, with relative risks (RR) of 2.80, 3.07, 3.55 and 2.12, respectively. These alleles are in strong linkage disequilibrium, and their possible relative contributions in predisposition to SLE are difficult to distinguish. The strongest association was found for DQA1*0501, which is in linkage disequilibrium with DRB1*03 as well as DRB1*11,12 (DR5). An increased frequency of DRB1*11,12 was observed (RR = 1.89, ns). No association with DRB1*15,16 (DR2) was found. The patients had a higher frequency of HLA class II homozygosity than the controls (RR = 5.05, p = 0.0005). When compared to the low-risk group (nonDRB1*03 class II heterozygotes), the cases homozygous for DRB1*03,DQA1*0501,DQB1*0201, known to be in linkage disequilibrium with the complement allele C4A*Q0, had the highest relative risk of developing SLE (RR = 16.39, p = 0.0002). However non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes had a higher relative risk (RR = 4.68, p = 0.0147) than DRB1*03,DQA1*0501,DQB1*0201 heterozygotes, known to carry the C4A*Q0 allele (RR = 2.72, p = 0.0088). This may suggest that HLA class II molecules are directly involved in susceptibility to SLE. PMID- 1440568 TI - Distribution of HLA-DQA1, -DQB1 and DRB1 alleles in black IDDM patients and controls from Zimbabwe. AB - We have used the XI Histocompatibility Workshop sequence-specific oligonucleotide probes to determine the DRB1, DQA1 and DQB1 genotypes by dot-blot hybridization of polymerase chain reaction (pcr)-amplified material from a homogenous black population in Zimbabwe. The DR4 subtype DRB1*0405, the DR3 subtype DRB1*0301, DQB1*0201 and DQB1*0302 and DQA1*0301 and DQA1*0501 were significantly increased in the IDDM group compared to the controls, whereas DRB1*11, DQB1*0602 and DQA1*0102 were significantly decreased. Taken together, the data show that susceptibility and resistance to IDDM are associated both with particular haplotypes and DQA1-DQB1 heterodimers without one or other being overriding. PMID- 1440569 TI - A silent mutation in HLA-DRB1*0301 can affect oligotyping. PMID- 1440570 TI - Genetic diversity within the HLA class II region: ten new DPB1 alleles and their population distribution. PMID- 1440571 TI - Cell cultures from cryopreserved human lung tissue. AB - To assess gene induction in primary human fibroblasts, we have developed a method for cryopreservation of lung biopsies in liquid nitrogen. Fresh biopsies (n = 10) were chopped into 5 x 5 mm pieces and transferred into an ice-cold freezing medium. Biopsies were kept on ice for 15 min, followed by further cooling of the tissue to -70 degrees C. With this method, lung biopsies were preserved for more than 1 year before they were used for generating cell cultures. There was no significant difference in the biological responsiveness of fibroblasts generated from immediately cultured lung biopsies compared with those from cryopreserved tissue. The doubling rate of fibroblasts from fresh tissue was 23.6 +/- 1.1 hr; compared to 23.5 +/- 1.5 hr for fibroblasts generated from cryopreserved tissue. PDGF-BB enhanced de novo synthesis of DNA 100 times, in both the immediately cultured fibroblasts and those generated from cryopreserved biopsies. Macrophages, dendritic cells and endothelial cells could also be recovered from cryopreserved lung tissue. This method permits long-term storage of lung tissue and the possibility of establishing primary cell lines from the same tissue at later times without appreciable changes in their cellular biological characteristics. PMID- 1440572 TI - The regulated expression of mRNA for Clara cell protein in the developing airways of the rat, as revealed by tissue in situ hybridization. AB - Tissue in situ hybridization has been used on sections of developing rat lung to follow the cellular sites of mRNA expression for a protein identified only in bronchiolar Clara cells. The mRNA for this Clara cell protein (CCP) was first detected on gestational day 16 in only one of the two types of tubules existing in the lung at this developmental stage. During the next 2 days CCP mRNA expression increased uniformly only in the epithelium lining the respiratory tubules. By gestational day 19, CCP mRNA expression became limited to secretory epithelial cells lining the bronchi, and terminal bronchioles. By neonatal day 1, an intense hybridization signal was observed along all of the conducting airways, but it was irregular due to the fact that expression of the CCP gene was limited to the secretory epithelial cells. In adult rats, CCP mRNA was expressed not only in secretory cells of the intrapulmonary airways at all anatomical levels, but also in secretory epithelial cells lining the trachea and its glands, as well as in specific alveolar cells thought to be type II pneumocytes. These findings demonstrate that the regulation of the CCP gene during lung development is a complicated process and that the expression of CCP mRNA does not parallel exactly the sequential development of the airways. PMID- 1440573 TI - Absence of sex differences in size of the genital ducts of the rat prior to embryonic day 15.5-16.0. AB - Sexual dimorphisms of the rat brain are generally believed to be brought about by the presence of testosterone during a critical period starting at embryonic day (ED) 17/18. In contrast, sex differences of diencephalic and mesencephalic dopaminergic neurons were observed to develop in cell cultures raised from ED 14 rat brains. This was interpreted as evidence indicating that sexual differentiation of certain neural systems may occur independently of gonadal hormones. To substantiate this claim, it was felt necessary to examine the rat embryo for clues to a possible existence of sex differences in hormonal environment prior to ED 17. Morphometry was applied to compare the development of male and female Wolffian and Mullerian ducts, both primary targets of hormones secreted from the male gonad. Diameters of serially cross-sectioned Wolffian and Mullerian ducts were measured in rats of ED 15.0 to ED 16.5. Females had thicker Mullerian ducts from ED 15.5 on. The first step of differentiation in males was the widening of the lumen and a slight increase of the outer diameter of the Wolffian duct at ED 16.0. The size differences of both ducts were most obvious in the vicinity of the lower half of the gonad. Except in Wolffian ducts of ED 16.5, sex differences were absent in the caudal parts of the ducts. It appears that gonadal androgen and Mullerian inhibiting substance do not affect the development of their classical target organs prior to ED 16.0 and ED 15.5, respectively. Furthermore, the first effects are paracrine in nature. There is no evidence for sex differences in systemic androgen environment until ED 16.5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440574 TI - Effects of exercise and food restriction on rat skeletal muscles. AB - Studies were undertaken to compare the effects of exercise and food restriction on body weight (BW), muscle weight (MW), muscle fiber size, and proportion of muscle fiber types. 20 male Fischer 344 rats were randomly assigned to four equal groups: ad libitum-fed control (AC), ad libitum-fed exercise (AE), food restricted control (RC) and food restricted exercise (RE). From 6 weeks of age, RC and RE rats received 60% of the daily food intake of AC and AE rats, respectively. At 7 months of age, AE and RE rats began 40-50 min of daily treadmill exercise. Running speed increased from 1.2 to 1.6 miles/hour and the grade increased to 15% during the first 2 weeks of training. After 10 weeks of training, rats were weighed, sacrificed, and the soleus (SOL), plantaris (PLN) and extensor digitorum longus (EDL) muscles were removed at in situ rest length, weighed, and quick-frozen. Standard histochemical assays were performed, and muscle fiber cross-sectional area was determined planimetrically. Training had little effect on MW or BW, but food restriction greatly reduced BW. This resulted in greater MW/BW ratio in RC and RE than AC and AE rats, respectively. Exercise also increased SOL muscle fiber area in ad libitum-fed but not food restricted rats resulting in smaller fibers in SOL of RE than AE. No changes in percentage of SOL fiber types occurred with food restriction or exercise. In PLN, the percentage of fast-twitch oxidative fibers of AE and RE was greater than in AC and RC, but there was no effect of food restriction or exercise on fiber area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440575 TI - Ultrastructural morphometry of matrical changes induced by exercise and food restriction in the rat calcaneal tendon. AB - The ultrastructural morphometry of collagen fibril populations in 24 calcaneal tendons obtained from 12 Fischer 344 rats were studied to elucidate matrical changes induced by food restriction and/or endurance exercise. Rats were randomly assigned to four equal groups: ad libitum control (AC), ad libitum exercise (AE), restricted diet control (RC) and restricted diet exercise (RE) groups. Beginning from 6 weeks of age, animals in the two food restriction groups were fed 60% of the mean food consumption of ad libitum fed rats. Then, starting from 6-7 months of age, the rats in the two exercise groups performed 40-50 min of treadmill running at 1.2-1.6 miles h-1 every day for a total of 10 weeks. Endurance training did not significantly alter body weight, but food restriction with or without exercise resulted in a significant loss of body weight. In ad libitum fed controls, food restriction alone did not significantly alter the mean collagen fibril CSA, but predisposed a preponderance of small-sized collagen fibrils. Endurance training per se induced a significant (32%) increase in mean fibril CSA (P less than 0.05), but this adaptive response to exercise was prevented by food restriction, as indicated by a 33% decline in fibril CSA (P less than 0.05). These findings demonstrate that dietary restriction modifies the adaptation of tendon collagen morphometry in response to endurance training, and that weight loss is better achieved with food restriction than endurance exercise. PMID- 1440576 TI - Ultrastructural morphometry of membrane-bound intracytoplasmic collagen fibrils in tendon fibroblasts exposed to He:Ne laser beam. AB - Collagen fibrils are not found in fibroblast cytoplasm except in certain pathological conditions or in the presence of drugs and other agents that accelerate collagen turnover. Because low energy laser photostimulation is both a non-pathogenic and non-chemical accelerator of collagen synthesis, its effects were studied on four groups of calcaneal tendons from 18 rabbits (1) to test the hypothesis that vacuolar fibrils are not produced exclusively by diseases and chemical agents, and (2) to compare the morphometry of matrical and vacuolar fibrils. The right calcaneal tendons of nine rabbits were surgically tenotomized and repaired; six of these were transcutaneously irradiated with He:Ne laser everyday. The right calcaneal tendon of six of the remaining nine rabbits were similarly irradiated with laser, but without prior tenotomy and repair. 21 days later, all tendons were fixed in situ and processed for electron microscopy. Fibril-bearing vacuoles were found only in fibroblasts of tenotomized laser irradiated tendons. Similar vacuoles were not seen in non-tenotomized laser irradiated tendons nor in non-irradiated tendons whether tenotomized or not. Mann Whitney U tests revealed no statistically significant differences in the cross sectional areas or diameters of matrical and vacuolar fibrils. These findings suggest (a) that matrical and vacuolar fibrils have a common origin, and (b) that vacuolar fibrils can be induced by a non-pathologic, non-chemical accelerator of collagen synthesis. PMID- 1440577 TI - Ultrastructural and mechanical properties of electrically inexcitable skeletal muscle fibers of the crustacean Atya lanipes. AB - Examination of the ultrastructure and mechanical activation of the ventro abdominal flexor muscle of the freshwater crustacean Atya lanipes shows that the fibers are of the long sarcomere, tonic type. The fibers possess an ample and well-organized internal membrane system, with extensive regions of T/SR dyad contacts near the ends of the A bands. An orbit of 10-12 thin filaments surrounds each thick filament. The lanthanum tracer method reveals a highly regular organization of the T-system, Z-tubules, and multiple internal clefts. Tension generation responds to extracellular potassium in a concentration dependent manner and is very slow. Mechanical activation is strictly dependent on extracellular Ca2+, even though these muscle fibers do not generate Ca2+ currents when depolarized. Tension development responds to caffeine and is also dependent on extracellular Na+, suggesting that Ca2+ release from the SR and Ca2+ influx via the Na/Ca exchanger intervene in mechanical activation. PMID- 1440578 TI - The innervation of the closer muscle of the mesothoracic spiracle of the locust. AB - The closer muscle of the mesothoracic spiracle of the locust, Schistocerca gregaria is innervated by two excitatory motoneurones and also by processes of a peripherally located neurosecretory cell. Within the muscle, ultrastructural studies show the presence of two types of excitatory nerve terminal which differ in the content of dense cored vesicles and in their distribution. The ventral segment of the muscle is innervated predominantly by terminals with small clear vesicles and only an occasional dense-cored vesicle. The central part of the muscle is innervated predominantly by terminals with small clear vesicles and larger numbers of dense-cored vesicles. The dorsal segment of the muscle is innervated exclusively by a neurosecretory type innervation. The small neurohaemal organ of the median nerve close to the spiracle muscle is immunoreactive to an antibody raised against bovine pancreatic polypeptide but no immunoreactive processes enter the muscle itself. The muscle possesses specific octopaminergic receptors that increase cyclic AMP levels and the possibility that the neurosecretory input to the muscle is provided by either a central or peripheral octopamine containing neurone is discussed. PMID- 1440579 TI - Quantitation of Sertoli cell-germ cell desmosome gap junctions in relation to meiotic divisions in the male rat. AB - Desmosome-gap (D-G) junctions were quantified in relation to germ cell meiosis in the male, specifically to test the hypothesis that the loss of these junctions is related to successful passage of cells through diplotene phase of Meiosis I and the two cytokineses that follow. Such a hypothesis has been proposed as the cause for the resumption of meiosis that occurs prior to ovulation in the female. D-G junctions were quantified in pachytene spermatocytes (stage XII), diplotene spermatocytes (stage XII), secondary spermatocytes (stage XIV) and step 1 spermatids (stage I). These were referred to as the cells of interest as compared with spermatocytes (zygotene spermatocytes, zygotene spermatocytes, pachytene spermatocytes, pachytene spermatocytes) in the same stages, respectively, that served as controls termed control cells. Since gap junctions are not easily recognized in the average sectioned profile of a desmosome-gap junction, only the desmosomal component was quantified. The data were expressed as both numbers and length of junctions per tubule, per cell profile and per unit lineal membrane length to overcome errors inherent in the methodologies utilized. There was no indication that numbers of junctions changed specifically in the cells of interest after passage through diplotene suggesting that these junctions do not have a comparable role in meiotic continuance in the male as proposed for the female. Interestingly, the control cells always showed greater numbers and length of junctions than the cells of interest suggesting that junction may relate more to the period of initiation of meiosis than to its continuance. PMID- 1440580 TI - Morphology of the liver of the brook lamprey, Lampetra lamottenii before and during infection with the nematode, Truttaedacnitis stelmioides, hepatocytes, sinusoids, and perisinusoidal cells. AB - Routine light microscopy and transmission and scanning electron microscopy were used to describe and compare the livers of larval lampreys, Lampetra lamottenii before and during infection of the bile ducts by the nematode, Truttaedacnitis stelmioides. The hepatocytes of uninfected animals differ from other lamprey species in that they contain abundant glycogen, smooth endoplasmic reticulum (SER), and lipoprotein indicating that the liver may be involved in glucose metabolism. Infestation of the biliary tree by T. stelmioides coincides with alterations to the hepatocytes. These changes include dilation of the bile canaliculi, smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER), and Golgi apparatus, swollen mitochondria in cells showing a high degree of hypertrophy, and an abundance of dense bodies. Following infection, the sinusoidal lumina became dilated and contain a moderate electron-dense precipitate, an abundance of melanomacrophages, lipocytes, and mononuclear cells. There is also a widening of the fenestrae of the sinusoidal endothelium following infection. Many of the changes in hepatocytes and sinusoids following parasite infections closely resemble those observed in hepatocytes in various pathologies and following experimental bile duct ligation and, therefore, are likely a consequence of increased biliary pressure due to bile duct obstruction. PMID- 1440581 TI - Role of the dermal tracts in the pigment pattern of the frog. AB - The pigment pattern of the ventral skin of the frog Rana esculenta is compared in skin fragments grown for 24 hr with or without antiserum directed to fibronectin (anti-FN). Melanocyte-stimulating hormone (MSH) was added to the medium during the last hour in culture in order to enhance visibility of melanophores in the ventral region of the frog skin. Comparison of these two treatments provides information regarding the precise localization of melanophores in the dermal tracts and their involvement in the pigment pattern of the ventral frog skin. In this regard, the whitish pigment pattern of skin fragments is compared to the tiny black spots found on anti-FN treated skin fragments and the abundant blotchy spots found on skin cultured alone. The distribution of melanophores in the dermal tracts observed in vertical semithin sections is found to be related to the three different levels of the dermal tracts. This report demonstrates the importance of fibronectin as a substrate for the melanophore migration, the importance of the tract level for the melanophore localization both involved in the pigment pattern of the ventral skin. PMID- 1440582 TI - Receptor-mediated endocytosis of insulin by cultured endothelial cells. AB - Label-fracture immunochemistry and pre-embedding indirect immunocytochemistry were applied to investigate insulin uptake by endothelial cells. Freeze fracture replicas showed that a small percentage of native insulin receptors are associated with non-coated pits (4%) and coated pits (2%). After warming, receptor bound insulin became increasingly associated with such endocytotic vesicles. After 2 min the percentage of detectable insulin associated with non coated and coated pits increased to 16% and 8%, respectively. Pre-embedding immunocytochemical localization of insulin gave results consistent with those obtained from the label-fracture studies. Both non-coated and coated vesicles appeared labelled after 5 min of warming. Non-coated vesicles contained 25% of the cell associated insulin while 9% was associated with coated pits and vesicles. After 10 min of warming, 9% of label was located in non-coated vesicles and 7% in coated vesicles. A large proportion (29%) of the label was found in tubular-vesicular endosomes at this time. After 15 min of warming, 30% of the remaining cell-associated gold label was found in multivesicular bodies. These experiments demonstrate that insulin uptake by endothelium is mediated by both coated and non-coated vesicles and that, once internalized, insulin is routed through endosomal pathways that primarily result in transcytosis. PMID- 1440583 TI - A simple in vitro method for raising monoclonal antibodies to cochlear proteins. AB - Monoclonal antibodies have been produced to mammalian hair cell antigens using a simple in vitro kit. Antigen was crudely prepared from dissected cochlear tissue by detergent extraction. There was no need to purify hair cells. Hybridoma supernatents were screened most efficiently on dissociated cells fixed with acetone. The immunisation method is sensitive to nanograms of antigen and can generate responses to conserved or weak antigens. The kit requires very little previous experience with cell culture and generates monoclonal antibodies within 3-4 weeks. It has overcome a number of problems with production of antibodies to hair cells and it should prove to be a very valuable tool in many laboratories. PMID- 1440584 TI - Changes of the Golgi apparatus and lysosomes during decidualization in mice. AB - The Golgi apparatus of the endometrial stromal cells of pregnant mice increases in size simultaneously with the differentiation of stromal cells into decidual cells. The activity of acid phosphatase in this organelle increases during this stage. On the other hand, the involuting decidual cells show morphological and cytochemical signs of Golgi regression (dilated cisternae, lack of enzymatic activity) together with the finding of numerous, pleomorphic lysosomes that have intense cytochemical label. These results confirm morphological data suggesting that decidual cell death occurs by autophagic degeneration. PMID- 1440585 TI - Perinuclear cytoskeleton of acrosome-less spermatids in the blind sterile mutant mouse. AB - The perinuclear cytoskeleton of mammalian spermatids is thought to play a major role in nucleus-acrosome association and in shape changes of the head during spermiogenesis. To test these hypotheses acrosome-less spermatids in blind sterile mutant mice were investigated for the development of the subacrosomal layer. Immunogold procedures were used for the detection of actin and calmodulin. In addition to various other abnormalities many acrosome-less round and elongating spermatids developed a subacrosomal layer with an actin and calmodulin distribution similar to that observed in normal spermatids. However, in mutant elongating spermatids the apical part of the nucleus was truncated and/or folded. The expected elongation and shaping of the nucleus only occurred in its caudal part associated with an hypertrophied and somewhat ectopic manchette. These abnormalities and those previously observed in mutant and experimental models indicated that the subacrosomal layer may form independently of the acrosome. It is suggested that the subacrosomal filamentous actin is a transitory scaffolding which might be involved in the assemblage of other proteins of the perinuclear cytoskeleton. However, by itself, this layer is not sufficient to ensure a normal shaping of the nucleus. Acrosome-nucleus interactions mediated by the subacrosomal layer seem necessary to shape the cranial spermatid head. The manchette appears to be involved only in the caudal nuclear shaping. PMID- 1440586 TI - Demonstration of the capacity of nacre to induce bone formation by human osteoblasts maintained in vitro. AB - Nacre implanted in vivo in bone is osteogenic suggesting that it may possess factor(s) which stimulate bone formation. The present study was undertaken to test the hypothesis that nacre can induce mineralization by human osteoblasts in vitro. Nacre chips were placed on a layer of first passage human osteoblasts. None of the chemical inducers generally required to obtain bone formation in vitro was added to the cultures. Osteoblasts proliferated and were clearly attracted by nacre chips to which they attached. Induction of mineralization appeared preferentially in bundles of osteoblasts surrounding the nacre chips. Three-dimensional nodules were formed by a dense osteoid matrix with cuboidal osteoblasts at the periphery and osteocytic-like cells in the center. These nodules contained foci with features of mineralized structures and bone-like structures, both radiodense to X-ray. Active osteoblasts (e.m.) with abundant rough endoplasmic reticulum, extrusion of collagen fibrils and budding of vesicles were observed. Matrix vesicles induced mineral deposition. Extracellular collagen fibrils appeared cross-banded and electrodense indicating mineralization. These results demonstrate that a complete sequence of bone formation is reproduced when human osteoblasts are cultured in the presence of nacre. This model provides a new approach to study the steps of osteoblastic differentiation and the mechanisms of induction of mineralization. PMID- 1440587 TI - Ultrastructure of carotid baroreceptors in the goat. AB - The initial segment of the occipital artery of the goat appears modified under the electron microscope; endothelial cells are low cuboidal, the tunica media contains many elastic lamellae, and there are few smooth muscle cells. Free afferent nerve endings are seen in this modified arterial wall. They closely resemble the presumptive baroreceptor endings reported in other mammals in their mitochondrial content and abnormal organelles and are interpreted as solely adapting baroreceptors. Special topographical relations between the endings and elastic or collagen fibres do not occur, but microfilaments are present in the vicinity of these endings. Presumptive adrenergic efferent endings are not found in the region of the baroreceptors. We suggest that this zone of the occipited artery is homologous to the carotid sinus. PMID- 1440588 TI - Stellate cells of aortic intima: I. Human and rabbit. AB - Stellate cells hitherto accounted exclusively in the innermost elastic hyperplastic layer were already reported to inhabit human aortic intima. The present paper shows that most of these cells are situated just beneath the endothelium. Stellate cells also appear in the deendothelialization-induced myointimal thickening of rabbit aorta. In the myointimal thickening these cells were revealed in the direct proximity to the endothelium. A conclusion is available that the previously demonstrated polymorphism of human aortic intimal cells may be reproduced in a simple experimental model, which gives new possibilities for the study of the cellular polymorphism in the vessel wall. PMID- 1440589 TI - Calcium-binding proteins in chemoreceptors of Xenopus laevis. AB - Calcium-binding proteins were investigated immunohistochemically in chemo receptors of the olfactory epithelium and taste buds of the clawed frog, Xenopus laevis. Calmodulin-, S-100- and calbindin-immunoreactive material were found in sensory cells of the olfactory epithelium; however, parvalbumin-like material was absent in these cells. Taste buds of the palate showed calmodulin-, S-100- and parvalbumin-immunoreactive material in sensory cells, while calbindin immunoreactive material in supporting cells. Merkel cells, surrounding the base of the taste buds in a ring-like manner, exhibited calmodulin- and S-100 immunoreactive material. PMID- 1440590 TI - The role of the rat submandibular gland in the excretion of bis (tributyltin) oxide: electron microscopy, X-ray microanalysis and atomic absorption analysis. AB - The role of the submandibular glands in the excretion of parenterally administered bis (tributyltin) oxide (TBTO) was studied. Fine structural alterations of the submandibular glands were observed with an electron microscope. Accumulation sites of TBTO were determined with an X-ray microanalyzer and tin concentrations in saliva and blood were measured by atomic absorption spectrophotometry. PMID- 1440591 TI - [The clinical case. Hair loss for three months in a dog]. PMID- 1440592 TI - [Diagnostic procedure in polydipsia]. PMID- 1440593 TI - [Birth injuries in calves and perinatal calf losses in a large dairy herd]. AB - Post-mortem examinations were carried out on 65 calves which were stillborn or died within 24 hours of birth. All calves came from a large dairy unit with about one thousand cattle of the Schwarzbuntes Milchrind breed. To evaluate the perinatal losses, the farm records of parturitions from 1985-1990 were used. The calves had gross damage of the CNS, the musculature, subcutaneous tissue and internal organs such as lung and intestines. It may be assumed that a lesser degree of similar damage would also be present in the surviving calves. The level of perinatal losses is determined particularly by deaths following prolonged parturition due to foetal oversize in heifers and young cows, but also by the birth of immature calves of low weight after pregnancy of normal or decreased duration and by twin pregnancies with high total calf mass and relative immaturity of the calves. PMID- 1440595 TI - [Ocular manifestations of systemic diseases in birds. Part 2]. AB - Among the representatives of the class aves, ocular lesions may be a particularly strong indicator of systemic disorders. A causative diagnosis of ocular lesions may be vital for the avian patient, not only as a basis for effective therapy of the primary disease, but also for saving the vision, as birds orientate themselves primarily by vision. The following paper presents a synopsis of important ocular disorders in avian patients that are either pathognomonic for certain disorders or, when considered in conjunction with other organic diseases, enable a specific diagnosis. Bacterial and parasitic infections were already described in part 1 of this paper. Part 2 gives outlines of possible viral etiologies and noninfectious diseases. PMID- 1440594 TI - [Concentration of Fe, Fe-binding capacity, Cu and Zn in the plasma of piglets before and after oral administration of iron sulfate solution]. AB - In piglets, the influence of the ingestion of Fe-enriched faeces, of the oral application of Fe-dextran (containing 150, 200 or 250 mg Fe) up to the 8th hour as well as the intramuscular injection of Fe-dextran (150 mg Fe) on the 2nd and 3rd day after birth on Fe-resorption was analysed. On the 5th to the 7th and on the 12th to the 14th day after birth the highest increase in the Fe-concentration and the highest values of the Fe-binding capacity of the plasma after the oral application of a solution of Fe-sulphate (containing 20 mg Fe/kg body weight) were confirmed in the piglets with the ingestion of Fe-enriched faeces and in the control piglets without Fe-supplementation. The increase of the iron concentration in the plasma induced a decrease in the concentration of Cu in some cases and of Zn in the plasma in most cases. The biggest increase in body weight was established in the piglets that ingested Fe-enriched faeces. PMID- 1440596 TI - [Respiratory support techniques in foals in a newborn intensive care unit for large animals]. AB - Various techniques for support and control of respiration in neonatal foals are described. It is crucial to evaluate respiration through frequent arterial blood gas analysis. Details for blood sampling from the metatarsal arteries and interpretation of results are provided. Typical diseases in newborn foals, which cause hypoxemia and/or hypercapnia and can be indications for respiratory support are apnea, hypopnea, pulmonary atelectasis, surfactant deficiency, meconium-, fetal fluid- and milk aspiration, maladjustment syndrome, cardiovascular abnormalities, anemia, airway obstruction, compromised lung expansion, increased abdominal pressure and pneumonias. Oxygen insufflation can be delivered through an intranasal tube. Positive pressure ventilation is best accomplished via an endotracheal tube. A nasogastric tube is inserted for enteral nutrition, application of drugs and checking for gastric reflux. Details for insertion of endotracheal and nasogastric tubes are given. Positive pressure ventilation can be achieved by manual ventilation with a rebreathing resp. resuscitator bag and mechanical ventilation with a respirator. Management and control of mechanical ventilation as well as intensive care and monitoring of foals are described. PMID- 1440597 TI - [Riding arenas and different riding track surfaces in relation to the airway contamination in horses. Laboratory studies on riding surfaces]. AB - 29 samples of commonly used surfaces were tested for their water characteristics (litre weight, water capacity, water binding, water evaporation) and their contribution to airborne fungal spores (dust formation, dust setting). The results are discussed in comparison to the literature with regard to the environment. The results are: 1. Any surface--no matter of what material- eventually causes air pollution with fungal spores and dust. 2. Correct watering prevents air pollution by any surface. 3. Artificial products have no advantage over natural materials in the parameters tested. 4. The question of proper disposal of old surface material has to be clarified before purchase. The results show that a mixture of sand and wood shavings should be recommended as a surface for indoor arenas, especially in regard to environmental protection and proper disposal. PMID- 1440598 TI - [Pathology of the retina]. AB - Degenerations (atrophies) of the retina are divided into primary (hereditary) and secondary forms including glaucomatous retinopathy of retinal atrophy. The pathogenesis of inflammation of the retina is considered. This condition generally appears in association with inflammation of the choroid (chorioretinitis), but can also occur as an isolated inflammatory condition during infectious disease (distemper). The functional conditions for retinal detachment, its rhegmatogenous and nonrhegmatogenous types, as well as the consequences of retinal detachment are described. Comparison of the pathology of retinal tumors shows that retinoblastoma is not known in animals. However, neuroepithelial tumors like the so-called acquired adenoma and adenocarcinoma of the mature ciliary epithelium as well as the rare congenital tumors of the embryonic neuroepithelium i.e. the medulloepithelioma and the ganglioneuroma are seen in animals. Finally, the rare but not unusual parasitic retinopathies are mentioned. PMID- 1440599 TI - [Malignant hyperthermia as a complication of anesthesia in the dog]. AB - A moderate malignant hyperthermia developed in a Labrador Retriever anaesthetized with isoflurane for a femoral shaft fracture repair. Signs of malignant hyperthermia included progressive increases in PETCO2 and rectal temperature up to 39.8 degrees C, tachycardia, cyanosis, and elevated serum levels of potassium, inorganic phosphorus, AST, CK and alkaline phosphatase. Treatment initiated in the early recovery period consisted of hyperventilation with 100% oxygen, stomach lavage with iced water, body surface cooling, and intravenous administration of cold isotonic saline solution. Cooling was continued until the rectal temperature had dropped to 37.3 degrees C. After treatment the dog recovered uneventfully. Clinical signs, pathophysiology, therapy, prevention of malignant hyperthermia and its association with other disorders are discussed. PMID- 1440600 TI - [The diagnostic value of sonography in the clinical picture of pyometra in the dog]. AB - Experiences of the diagnostic value of ultrasonography of pyometra in the bitch are reported. The different ultrasound scans of the uterus are illustrated. Results are compared with clinical diagnosis and pathophysiological findings after laparotomy and surgical removal of the uteri. Very close correlation (r: 0.985, p < 0.001) was found between the postoperative macroscopic and the ultrasound scan measurements of the uterus. Accuracy of the ultrasound diagnosis and reasons for false and questionable results are discussed. In summary, ultrasonography is an accurate procedure for the qualitative and quantitative examination and diagnosis of canine pyometra. PMID- 1440601 TI - [The radiologic differential diagnosis in girth increase of the gastric cavity and the body in lizards (Squamata: Sauria)]. AB - The extended girth is one of the few important and obvious symptoms in lizards (Sauria). Radiological examination proved to be the most important method in the clinical diagnostic procedure. Standard and contrast images using oral and cloacal application of barium sulphate or iodophoric contrast media were frequently indicated. Based on 442 X-rays from 162 lizards out of 20 genus the significant radiological, physiological and pathological findings are described. Frequent findings were dystocia in oviparous and viviparous lizards (18.5%), gastritis and enteritis (12.3%), ascites (9.3%), fractures of the spine and osteodystrophia (9.3%), obstipation (6.2%), foreign bodies (4.9%), neoplasia (4.3%) and enteroliths (4.3%). Pneumonia (3.7%), was as frequent as the physiological lung tympany (3.7%). Pregnancy was the most frequent physiological finding (8%). The radiological findings, are described in detail, especially in regard to differentiation between physiological and pathological conditions. PMID- 1440602 TI - Effects of ethanol on cocaine metabolism: formation of cocaethylene and norcocaethylene. AB - The coabuse of cocaine and ethanol occurs with high frequency and increases the risk of cocaine-related morbidity and mortality. The mechanisms mediating the toxic interactions of cocaine and ethanol are not clearly defined. This study examined the effects of acute ethanol administration on the metabolism of cocaine in the male Wistar rat. Intraperitoneal administration of 2 g/kg ethanol 30 min prior to administration of 25 mg/kg cocaine resulted in the formation of two ethylated derivatives of cocaine, benzoylecgonine ethyl ester (cocaethylene) and benzoylnorecgonine ethyl ester (norcocaethylene) in liver, brain, and serum. Fifteen minutes after cocaine administration, the tissue levels of cocaethylene were 22, 10, and 9% of the cocaine recovered from liver, serum, and brain, respectively. Ethanol pretreatment increased cocaine concentrations in liver and benzoylnorecgonine concentrations in liver and serum. The increased morbidity and hepatotoxicity seen with acute combined administration of cocaine and ethanol may be due to the formation of the toxic ethylated and N-demethylated metabolites of cocaine. Ethanol pretreatment decreased benzoylecgonine concentrations in serum and liver. The most important consequence of ethanol-induced inhibition of the normally rapid hydrolysis of cocaine to benzoylecgonine may be a decrease in benzoylecgonine-mediated vasoconstriction. PMID- 1440603 TI - Sulfur mustard-induced microvesication in hairless guinea pigs: effect of short term niacinamide administration. AB - It has been postulated that sulfur mustard (HD) damage may activate poly(ADP ribose) polymerase (PADPRP), resulting in depletion of cellular NAD+. This biochemical alteration is postulated to result in blister (vesicle) formation. It has been previously demonstrated that niacinamide (NAM), an inhibitor of PADPRP and a precursor for NAD+ synthesis, may be useful as a pretreatment compound to reduce HD-induced microvesication. The present study was undertaken to determine whether niacinamide's protective action could be extended beyond 24 hr and if the degree of microvesication is related to changes in skin NAD+ content. HD exposures were made by vapor cup to hairless guinea pigs. Niacinamide (750 mg/kg, ip) given as a 30-min pretreatment did not reduce the degree of microvesication 72 hr after HD compared to saline controls. However, niacinamide given as a 30 min pretreatment and at 6-, 24-, and 48-hr after HD, exhibited a 28% reduction in microvesication 72 hr after HD. Skin NAD+ content at 72 hr after HD was depleted by approximately 53% in the saline and NAM-treated groups. Skin NAD+ content was depleted despite NAM administration. Niacinamide did not reduce the degree of erythema at 48 or 72 hr. These results suggest that niacinamide's protective effect against HD-induced microvesication may be extended for at least 72 hr, but NAM levels must be sustained during the post-HD period. The link between maintenance of skin NAD+ and reductions in microvesication is still uncertain. PMID- 1440604 TI - Paraoxon toxicity is not potentiated by prior reduction in blood acetylcholinesterase. AB - The role of blood acetylcholinesterase in moderating the effects of organophosphate challenge in rats was tested. Adult male rats (n = 42) were injected (iv) either with monoclonal antibodies (MAb) to rat acetylcholinesterase (EC 3.1.1.7; AChE) or normal mouse IgG (controls). Two days later, the rats were injected (sc) with either a mild (0.17 mg/kg) or moderate dosage (0.34 mg/kg) of paraoxon or with vehicle. Neurological integrity was assessed by a functional observational battery followed by motor activity, 3 to 4 hr after dosing. Blood, brain, and diaphragm tissues were then collected for determination of AChE activity. MAb treatment reduced whole blood and plasma AChE activity by 32 and 90%, respectively, but did not affect neurobehavioral parameters or the AChE activity of brain or diaphragm. The paraoxon challenge produced dose-related neurobehavioral changes and inhibition of brain and diaphragm AChE activity to the same extent in IgG- and MAb-treated rats. Thus, significant loss in blood AChE alone produced no detectable neurobehavioral deficits and did not alter the subsequent responses to paraoxon challenge. PMID- 1440605 TI - Hydrolysis of pyrrolizidine alkaloids by guinea pig hepatic carboxylesterases. AB - Two carboxylesterases (GPL1 and GPH1) were isolated from guinea pig hepatic microsomes and assayed for activity using the following pyrrolizidine alkaloids (PAs): seneciphylline (SNP), monocrotaline (MCT), and a mixture of senecionine (SEN) and integerrimine (INT) referred to as SEN-INT. GPH1 was able to effect the hydrolysis of all PAs, however, only minimal activity was seen for SEN-INT. The specific activity of GPL1 for p-nitrophenyl acetate was four times that of GPH1, but the former showed no activity toward PAs. The molecular weights and pIs were determined for both enzymes, and the Michaelis-Menten constants for two PAs, SNP and MCT were obtained using GPH1. The response to inhibitors confirmed GPH1 as a type B serine hydrolase although it was also inhibited by HgCl2. The isolation of a PA active esterase from the guinea pig may help to explain the resistance of this animal to PA intoxication, while enzyme substrate specificity may explain how the guinea pig's susceptibility to PA intoxication can differ toward various PAs. PMID- 1440606 TI - Modulation of M1 and M2 muscarinic receptor subtypes following repeated organophosphate exposure in rats. AB - Repeated exposure to organophosphates has been shown to cause a decrease in muscarinic cholinergic receptors in the central and peripheral nervous system. The present study measured the modulation of M1 and M2 muscarinic receptor subtypes in rat brain areas during and following a 2-week daily exposure to the organophosphate disulfoton. The radioligands [3H]telenzepine and [3H]AFDX 384 were utilized to label M1 and M2 receptors, respectively. The study found comparable down-regulation in both [3H]telenzepine- and [3H]AFDX 384-labeled receptors in cortex, hippocampus, and striatum during exposure. Recovery of M2 subtype was slower than recovery of M1, especially in the hippocampus. The results suggest that M1 and M2 receptor subtypes may be similarly regulated in response to subchronic exposure to organophosphates, but that recovery of receptor subtypes to control levels may be governed by distinct factors. PMID- 1440607 TI - Inhibition of acute TCDD toxicity by treatment with anti-tumor necrosis factor antibody or dexamethasone. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) acute toxicity is characterized in part by a wasting syndrome with depletion of adipose tissue. Tumor necrosis factor (TNF) induces a similar response during chronic infection. The similarities of these toxic effects led to a hypothesis that TNF plays a role in TCDD acute toxicity. To test this hypothesis pharmacologic doses of an antibody specific for murine TNF and the potent anti-inflammatory agent Dexamethasone (DEX) were used to inhibit TCDD toxicity in mice. TNF antibody treatment resulted in a 54% reduction in TCDD-mediated mortality while DEX treatment, a glucocorticoid agonist that inhibits transcription of TNF, reduced mortality by 92%. Cyp 1A1 induction, the most commonly measured TCDD-mediated response, was not blocked by DEX, demonstrating separation of this biochemical effect from acute toxic responses to TCDD. These data suggest that TCDD-mediated changes in the TNF pathway may be an important mechanism for acute TCDD toxicity. PMID- 1440608 TI - 1,2-Dichloropropane is a renal and liver toxicant. PMID- 1440609 TI - Effect of ozone on platelet activating factor metabolism in phorbol differentiated HL60 cells. AB - The mechanisms of ozone (O3) toxicity in the lung may involve the formation of lipid inflammatory mediators. We have previously demonstrated that exposure to O3 in vitro results in increased accumulation and release of platelet activating factor (PAF) in the macrophage-like cell line HL60 differentiated with phorbol ester (dHL60). In the present study we have examined possible biochemical mechanisms responsible for the O3-induced increase in PAF levels in dHL60 cells. Specifically, we studied the effect of O3 on phospholipase A2 (PLA2), acetyltransferase, acetylhydrolase, and reacylation activities. dHL60 cells were exposed to 1.0 ppm O3 or air alone. O3 exposure was found to significantly decrease dHL60 cell acetylhydrolase activity by 36%. Additional experiments demonstrated that extracellular acetylhydrolase activity, but not intracellular acetylhydrolase activity, was inhibited by O3 exposure of dHL60 cells. O3 exposure resulted in a small (13%) but statistically significant reduction in reacylation activity in dHL60 cells. In addition, a significant (22%) contribution of PLA2 activation to the O3-induced increase in PAF levels was also found. Basal and calcium ionophore-induced acetyltransferase activity was found to be unaffected by exposure of dHL60 cells to O3. These data suggest that in vitro exposure to O3 affects both synthetic and degradative pathways of PAF metabolism in dHL60 cells. PMID- 1440610 TI - Physiologically based pharmacokinetic model for methanol in rats, monkeys, and humans. AB - The pharmacokinetics of methanol and formate were characterized in male Fischer 344 rats and rhesus monkeys exposed to methanol vapor concentrations between 50 and 2000 ppm for 6 hr. End-of-exposure blood methanol concentrations were not directly proportional to the atmospheric concentration. The methanol exposures did not cause an elevation in blood formate concentrations. After an intravenous dose of [14C]methanol in rats, metabolism, exhalation, and renal excretion contributed 96.6, 2.6, and 0.8%, respectively, to the elimination of blood methanol concentrations. These values and the calculated renal methanol extraction efficiency (0.007) are nearly identical to those for humans after low doses of methanol. A physiologically based pharmacokinetic model was developed to simulate the in vivo data. In order to simulate the observed blood methanol concentrations in the inhalation studies in rats, a double pathway for methanol metabolism to formaldehyde was used. One path used rodent catalase Km and Vmax values and the other used a smaller Km and Vmax to simulate an enzyme with a higher affinity and lower capacity. The lack of proportionality observed in end of-exposure blood methanol concentrations may be due to saturation of an enzyme with higher affinity and lower capacity than catalase. The physiologically based pharmacokinetic model was modified to simulate the monkey data and was scaled-up for humans. In order to simulate the monkey blood methanol concentrations, the use of rodent catalase parameters for methanol metabolism was required. This finding suggests that primates and rodents may be similar in the initial step of methanol metabolism after low methanol doses. Previously published human urinary methanol excretion data was successfully simulated by the model. The models were used to predict the atmospheric methanol concentration range over which the laboratory species exhibit quantitative similarities with humans. Below 1200 ppm, all three species exhibit similar end-of-exposure blood methanol concentrations and a linear relationship between atmospheric and blood methanol concentrations. At higher atmospheric concentrations, external and internal methanol concentrations increase desparately, suggesting that delivered dose rather than exposure concentration should be used in interpreting data from high-dose studies. PMID- 1440611 TI - Acute ozone-induced lung injury in rats: structural-functional relationships of developing alveolar edema. AB - As part of a study on the effects of acute ozone stress on the lung surfactant system, we correlated morphometric, biochemical, and functional indices of lung injury using male rats exposed to 3 ppm ozone for 1, 2, 4, and 8 hr. Evaluation of lung mechanics, using the Pulmonary Evaluation and Diagnostic Laboratory System, revealed a significant decrease in dynamic lung compliance (ml/cmH2O/kg) from a control value of 0.84 +/- 0.02 (SEM) to 0.72 +/- 0.04 and 0.57 +/- 0.06 at 4 and 8 hr, respectively. At 2 hr there was a transient increase in PaO2 to 116 torr (control = 92 torr) followed by a decrease at 4 hr (65 torr) and 8 hr (55 torr). Morphometry of lung tissue, fixed by perfusion of fixative via the pulmonary artery at 12 cm H2O airway distending pressure, demonstrated an increase in the area of the intravascular compartment at 8 hr, in association with a 65 and 39% replacement of the alveolar area by fluid in ventral and dorsal lung regions, respectively. There was a positive correlation (r = 0.966) between alveolar edema and transudated proteins in lavage fluid. A stepwise multiple regression model, with edema as the dependent variable, suggested that pulmonary vasodilatation, hypoxemia, and depletion of surfactant tubular myelin in lavage fluid were indices for predicting alveolar edema. In a second model, with lavage protein concentration as the dependent variable, decreasing dynamic compliance and hypoxemia were predictors of progressive, intraalveolar transudation of plasma proteins. The above structural-functional relationships support the concept that ozone-induced high-protein alveolar edema is pathogenetically linked to pulmonary hyperemia, deficiency of surfactant tubular myelin, and associated lung dysfunctions. PMID- 1440612 TI - Mercury distribution in the rat brain after mercury vapor exposure. AB - Brown Norwegian rats were exposed to mercury vapor at a concentration of approximately 1 mg/m3 for 5 weeks 24 hr/day 7 days a week and 6 hr/day 3 days a week, respectively. The total mercury absorption was calculated to 264 and 35 micrograms per week and 100 g body weight. The mean blood mercury concentration was 0.25 +/- 0.03 and 0.09 +/- 0.01 microgram/g, and the total concentration in the brain was 5.03 +/- 0.73 and 0.71 +/- 0.10 microgram/g tissue, respectively. The mercury distribution in the brains was examined using a method based on chemographic principles. Mercury was found primarily in the neocortex, in the basal nuclei, and in the cerebellar Purkinje cells. This distribution pattern corresponded to the pattern of inorganic mercury described after exposure to methyl mercury. Distribution of mercury after administration of different mercury compounds is discussed. PMID- 1440613 TI - Comparison of cell-permeable calpain inhibitors and E64 in reduction of cataract in cultured rat lenses. AB - E64, an inhibitor of calpain (EC 3.4.22.17) and other cysteine proteases, slows the rate of formation of cataract in cultured rat lenses. The purpose of this study was to determine (1) why E64, a charged compound with little cell permeability, was effective in reducing cataract in cultured lens and (2) whether uncharged more permeable protease inhibitors are more effective than E64 in preventing cataract. Results showed that E64 entered the lens, but only after the lens was treated with the calcium ionophore, A23187, or sodium selenite, both of which cause cataracts. Therefore, the uptake and subsequent effectiveness of E64 may be related to a generalized increase in membrane permeability during induction of cataract in culture. Three protease inhibitors, reported to have improved cell permeability, were compared with E64 for their ability to prevent cataracts in cultured lenses. cBz-ValPheH, calpain inhibitors I and II, are uncharged-aldehyde inhibitors of calpain. Calpain inhibitors I and II even at high concentrations were not effective at reducing lens opacity caused by calcium ionophore and were toxic to the lens. cBz-ValPheH, which is slightly toxic to the lens, was able to significantly reduce lens opacity induced by calcium ionophore. The presented data suggest that while E64 decreases cataract formation in cultured lens, the more cell permeable inhibitor, cBz-ValPheH, may have greater efficacy as an anticataract drug in vivo. PMID- 1440614 TI - Determination of mutagenicity in tissues of transgenic mice following exposure to 1,3-butadiene and N-ethyl-N-nitrosourea. AB - 1,3-Butadiene (BD) is carcinogenic in the B6C3F1 mouse in multiple organs, including lung and liver. We conducted a study to measure the frequency of BD mutations in mouse tissues using a transgenic mouse (Muta mouse; MM). MM is a BALB/c x DBA/2 (CD2F1) mouse that has a bacteriophage lambda shuttle vector with the target gene lacZ integrated into the mouse genome. Mice were exposed by inhalation to 625 ppm BD (6 hr/day) for 5 days and the lacZ- mutant frequency (mf) was determined in lung, bone marrow, and liver. The lacZ- mf in lung increased twofold above air-exposed control animals, but the bone marrow and liver samples did not exhibit an increase above background. N-ethyl-N-nitrosourea (250 mg/kg ip) was mutagenic in all three tissues examined. Studies on the biotransformation of BD using MM liver microsomes showed that the ratio between the rates of BD bioactivation to BD monoepoxide (BMO) and hydrolysis of BMO by epoxide hydrolases was approximately 40% less than this ratio using B6C3F1 mouse liver microsomes. Quantitation of adducts of BMO to N-terminal valine in hemoglobin (Hb) in the MM revealed an adduct level of 3.7 pmol/mg globin. Using this value, the predicted Hb adduct level in MM would be approximately one-half of that measured in the B6C3F1 mouse following similar exposures. These results indicate that BD induces mutations in vivo in a known murine target tissue, but strain differences in the biotransformation of BD should be considered in comparing the susceptibility of transgenic mouse strains to mutation. PMID- 1440615 TI - Dietary 2,3,7,8-tetrachlorodibenzofuran in rainbow trout: accumulation, disposition, and hepatic mixed-function oxidase enzyme induction. AB - Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to dietary 2,3,7,8 [3H]tetrachlorodibenzofuran (TCDF) (0.36 to 42.8 ng g-1) and accumulation, tissue distribution, biotransformation, and hepatic monooxygenase enzyme (MO) induction were studied. The assimilation efficiency of TCDF ranged from 49 to 62% in 30-day exposures and was independent of the TCDF level in the diet. Depuration half lives (whole body) of TCDF following 30-day exposure ranged from 40 to 77 days and were significantly more rapid in fish exposed to 42.8 ng g-1. Liver somatic index (LSI) and rate of increase in liver weight were elevated in fish exposed to 42.8 ng g-1 TCDF compared to controls. Exposure to 9.2 ng g-1 TCDF in the diet for 140 days also resulted in higher LSI values, as well as increased mortality (16%), but had no significant effects on growth. [3H]TCDF was found mainly in the carcass (63-74%) and GI tract (18-31%), with lesser amounts in liver (0.6-2.3%) during the 140-day exposure, primarily (> 98%) in the form of the parent compound. Radioactivity in bile was found mainly as a single polar transformation product by reverse-phase HPLC. Glucuronidase hydrolysis yielded a product with the retention time expected of hydroxylated TCDF, suggesting the presence of a glucuronide conjugate. MO enzyme induction measured by ethoxyresorufin-O deethylase (EROD) activity in liver (postmitochondrial supernatant) was 137.5 and 15 times higher than that in control fish after 30 days dietary exposure to 42.8 and 9.2 ng g-1, respectively. EROD activities were correlated with TCDF concentrations in liver (R2 = 0.59, N = 45). PMID- 1440616 TI - Rat lung metallothionein and heme oxygenase gene expression following ozone and zinc oxide exposure. AB - We have conducted exposures in rats to determine pulmonary responses following inhalation of two common components of welding fumes, zinc oxide and ozone. To examine their effects on target-inducible gene expression, we measured mRNA levels of two metal-responsive genes, metallothionein (MT) and heme oxygenase (HO), in lung tissue by RNA slot-blot analysis. A 3-hr exposure to ZnO fume via a combustion furnace caused a substantial elevation in lung MT mRNA at all concentrations tested. Exposures to 5 and 2.5 mg/m3 ZnO resulted in peak 8-fold increases in MT mRNA levels (compared to air-exposed control animal values) immediately after exposure, while 1 mg/m3 ZnO exposure caused a 3.5-fold elevation in MT mRNA. These levels returned to approximate control gene expression values 24 hr after exposure. In addition, ZnO exposure caused an immediate elevation in lung HO gene expression levels, with 8-, 11-, and 5-fold increases observed after the same ZnO exposure levels (p < 0.05). Like MT gene induction, HO mRNA values returned to approximate control levels 24 hr after exposure. In striking contrast to the induction of MT and HO gene expression after ZnO exposures, there was no elevation in gene expression following a 6-hr exposure to 0.5 and 1 ppm ozone, even when lungs were examined as late as 72 hr after exposure. Our results demonstrate the induction of target gene expression following the inhalation of ZnO at concentrations equal to, and below, the current recommended threshold limit value of 5 mg/m3 ZnO. Furthermore, the lack of effect of ozone exposure on MT and HO gene expression suggests no involvement of these genes in the acute respiratory response to this oxidant compound. PMID- 1440617 TI - Biotransformation and toxicity of acetaminophen in congenic RHA rats with or without a hereditary deficiency in bilirubin UDP-glucuronosyltransferase. AB - Acetaminophen is eliminated primarily by glucuronidation, thereby avoiding cytochrome P450-catalyzed bioactivation to a toxic reactive intermediate. Previous studies have shown that UDP-glucuronosyltransferase-deficient Gunn rats are more susceptible to acetaminophen toxicity than normal Wistar controls, from which the Gunn strain was derived. However, the Gunn and Wistar strains are not congenic, and differences in toxicologic susceptibility could be due in part to genetic differences other than UDP-glucuronosyltransferase activity. Accordingly, acetaminophen (750 mg/kg, ip) was administered to congenic RHA rats with normal (homozygous, RHA/++), moderately deficient (heterozygous, RHA/j+), and severely deficient (homozygous jaundiced, RHA/jj) activities of bilirubin UDP glucuronosyltransferase. Acetaminophen metabolites were measured by high performance liquid chromatography and production of the acetaminophen glucuronide conjugate was quantified by the area under plasma concentration-time curve (AUC) from 0 to 2 hr, standardized by the AUC value for acetaminophen in the same animal (glucuronidation ratio = AUC acetaminophen glucuronide/AUC acetaminophen). The 0- to 2-hr time period for AUC calculations was necessitated by the accumulation at later time points of glucuronide and sulfate conjugates in the plasma of animals experiencing severe nephrotoxicity. Acetaminophen bioactivation was quantified by the 24-hr urinary recovery of glutathione-derived conjugates. Hepatotoxicity and nephrotoxicity were assessed respectively by the peak concentrations of plasma alanine aminotransferase (ALT) and blood urea nitrogen (BUN). Glucuronidation of acetaminophen in RHA/jj rats (0.065 +/- 0.005) (mean +/ SE) was reduced 63% compared to the RHA/++ controls (0.17 +/- 0.01) (p < 0.05). RHA/jj rats demonstrated respective 230- and 7-fold increases in the peak plasma concentrations of ALT (17144 +/- 1014 vs 75 +/- 10) and BUN (128 +/- 23 vs 18.4 +/- 0.2) compared to congenic normal controls (RHA/++) (p < 0.05). Heterozygous animals (RHA/j+) demonstrated intermediary toxicity for both parameters (ALT = 2029 +/- 1581, BUN = 41 +/- 16, p < 0.05). Decreased glucuronide production correlated with elevations in ALT (r = -0.86, p < 0.001), while increased acetaminophen bioactivation correlated directly with both elevated ALT (r = 0.93, p < 0.001) and BUN (r = 0.83, p = 0.001). These results using congenic controls demonstrate that the enhanced susceptibility of UDP-glucuronosyltransferase deficient rats to acetaminophen toxicity is due to decreased glucuronidation resulting in enhanced bioactivation, rather than to other unappreciated genetic differences. PMID- 1440618 TI - Methylene dianiline: acute toxicity and effects on biliary function. AB - 4,4'-Methylene dianiline (4,4'-diaminodiphenylmethane, DAPM), which is used in the polymer industry, causes hepatobiliary damage in exposed humans. Our objectives were to characterize the acute toxicity of DAPM in liver, particularly on secretion of biliary constituents and on biliary epithelial cell gamma glutamyl transpeptidase (GGT) activity. Biliary cannulas were positioned in Sprague-Dawley male rats under pentobarbital anesthesia. After 1 hr of control bile collection, each rat was given 250 mg DAPM/kg (50 mg/ml) po in 35% ethanol or 35% ethanol only; bile was collected for a further 4 hr. Groups of rats were also examined for liver injury and biliary function at 8 and 24 hr after DAPM. Four hours after DAPM administration, main bile duct cells were severely damaged with minimal damage to peripheral bile ductule cells. Focal periportal hepatocellular necrosis and extensive cytolysis of cortical thymocytes occurred by 24 hr. Serum indicators of liver injury were elevated by 4 hr and continued to rise through 24 hr. By 4 hr, biliary protein concentration was increased 4-fold while concentrations of biliary bile salt, bilirubin, and glutathione were decreased by approximately 80, 50, and 200%, respectively. DAPM also induced a striking effect on biliary glucose with an approximately 20-fold increase. Histochemical staining of main bile duct GGT was absent by 8 hr after DAPM. Bile flow was diminished by 40% at 4 hr; three of five rats had no bile flow by 8 hr and none had any bile flow by 24 hr. These results indicate that DAPM rapidly diminishes bile flow and alters the secretion of biliary constituents and is highly injurious to biliary epithelial cells. PMID- 1440619 TI - The relationship between nickel chloride-induced peroxidation and DNA strand breakage in rat liver. AB - Inorganic nickel chloride induces hepatic DNA strand breaks, chromosome aberrations, and lipid peroxidation under in vitro and in vivo conditions. The objective of this research was to determine if a relationship exists between NiCl2 genotoxicity and lipid peroxidation in vivo. Male Sprague-Dawley rats (210 250 g) were dosed with 0.56 or 0.75 mmol/kg NiCl2 subcutaneously and euthanized after specific time periods, ranging from 30 min to 24 hr. Livers were perfused and excised for the measurement of nickel content using atomic absorption spectrometry, lipid peroxidation using a thiobarbituric acid assay, and DNA strand breakage using single-stranded DNA extraction and the diaminobenzoic acid assay. The lower dose (0.56 mmol/kg) did not induce lipid peroxidation or strand breakage. The higher dose (0.75 mmol/kg) induced DNA strand breakage at 4 hr and lipid peroxidation at 12 hr in rat liver. Nickel was seen to accumulate in liver nuclei of rats receiving 0.75 mmol/kg. Deferoxamine (1 g/kg, ip, 15 min before the NiCl2 injection) completely inhibited DNA strand breakage at 4 hr but had no effect on lipid peroxidation. This suggests that lipid peroxidation is not causally related to genetic damage. NiCl2-induced DNA strand breakage may be caused by the induction of the Fenton reaction, generating hydroxyl radicals. PMID- 1440620 TI - Plants with a reputation against snakebite. AB - Many plants are recommended in traditional medicine as active against various effects of snakebite. Few attempts have been made to investigate the veracity of these assertions in controlled experiments. Several workers, mainly Oriental, have investigated the reputation of such plants by performing in vitro and in vivo experiments in order to demonstrate whether there was any protective effect, using drugs or mixtures of drugs prepared using traditional formulae. In some studies, these extracts were administered to mice before or after treatment with different elapid or crotalid venoms. Other papers deal with selected compounds isolated from Schumanniophyton magnificum, Eclipta prostrata or Aristolochia shimadai, and their capacity to inhibit phospholipase A2 or other enzymes (e.g. ATPase) or for physiological and biochemical properties (such as effects on uterine tone or the protection of mitochondrial membranes). Japanese workers have described the antihaemorrhagic effect of persimmon tannin from Diospyros kaki. Atropine has been attributed a life-prolonging effect after black mamba venom treatment. Prolonged survival was also observed after pretreatment with extracts of Diodia scandens and Andrographis paniculata. Some authors have found little or no beneficial effects. The papers collected so far show that there are no systematic investigations in this field. PMID- 1440621 TI - Paralytic shellfish poison (saxitoxin family) bioassays: automated endpoint determination and standardization of the in vitro tissue culture bioassay, and comparison with the standard mouse bioassay. AB - Mouse neuroblastoma cells swell and eventually lyse upon exposure to veratridine, which, when added together with ouabain, enhances sodium ion influx. In the presence of saxitoxin (STX), which blocks sodium channels, the action of the other two compounds is inhibited and the cells remain morphologically normal. A tissue culture bioassay using mouse neuroblastoma cells, developed by Kogure and colleagues, takes advantage of these principles; in this bioassay, the fraction of the cells protected from the actions of ouabain and veratridine is in direct proportion to the concentration of STX and its analogues. We have modified this bioassay, improving its convenience and speed by eliminating the need to count individual cells to determine the saxitoxin equivalents, and instead have employed a microplate reader for automated determinations of absorbances of crystal violet from stained neuroblastoma cells. When these changes and other minor technical modifications were tested in the tissue culture bioassay systematically, we found the lower detection limit to be around 10 ng STX equivalents (eq) per ml of extract ( = 2.0 micrograms STX eq/100 g shellfish tissue). Our version of the tissue culture bioassay was compared with the standard mouse bioassay using 10 acid extracts of dinoflagellates (Alexandrium excavata and A. fundyense) and 47 AOAC extracts of shellfish tissues. The tissue culture bioassay provided results virtually identical to those obtained with the mouse bioassay (r > 0.96), and moreover, was considerably more sensitive. The results gained from high performance liquid chromatographic (HPLC) analysis of 12 of the same extracts were less consistent when compared with the results from both bioassay methods. The automated tissue culture (neuroblastoma cell) bioassay may be a valid alternative to live animal testing for paralytic shellfish poisoning. PMID- 1440622 TI - Identification of anatoxin-A in benthic cyanobacteria (blue-green algae) and in associated dog poisonings at Loch Insh, Scotland. AB - Dog deaths occurred in 1990 and 1991 after the animals drank water containing blooms of benthic cyanobacteria along the shoreline of Loch Insh, Scotland. Signs of poisoning in the affected animals and the high neurotoxicity of bloom extracts in laboratory bioassays indicated acute poisoning due to cyanobacterial neurotoxin(s). The neurotoxic blooms consisted largely of benthic Oscillatoria species which were also observed in the stomach contents of the poisoned dogs. Stomach contents were also neurotoxic in bioassays with the same signs of poisoning as the Oscillatoria blooms. The cyanobacterial alkaloid neurotoxin anatoxin-a was identified in bloom extracts and poisoned dog stomach contents by high-performance liquid chromatography and gas chromatography-mass spectrometry. A species of benthic Oscillatoria has been isolated from the neurotoxic bloom material and shown to produce anatoxin-a in laboratory culture. These findings are the first to associate anatoxin-a toxicoses with benthic, rather than planktonic, cyanobacteria. Procedures for anatoxin-a extraction and identification from the blooms and animal material are also detailed. PMID- 1440623 TI - Production of a monoclonal antibody against the thrombin-like enzyme, habutobin, from Trimeresurus flavoviridis venom. AB - We succeeded in producing a monoclonal antibody to the thrombin-like enzyme, habutobin, which was purified from crude venom of the snake Trimeresurus flavoviridis. The monoclonal antibody obtained belonged to IgG1, and its light chain consisted of a kappa-chain. The monoclonal antibody reacted specifically with habutobin and crude venom from T. flavoviridis but did not react with human thrombin or bovine thrombin on Western blotting. The concentration of habutobin and crude venom of T. flavoviridis, in vitro, could be measured by means of ELISA using the monoclonal antibody. Furthermore, the ELISA-double sandwich method employing this monoclonal antibody may represent a reliable method for determining the habutobin levels in the circulating blood. PMID- 1440624 TI - Variation and secretion of toxins in gastropod mollusc Niotha clathrata. AB - Nearly 300 specimens of the gastropod mollusc Niotha clathrata were collected in South Taiwan. All specimens were assayed for toxicity by the official method for tetrodotoxin (TTX). The frequency value of toxic specimens in N. clathrata was 30.0%, 68.0% and 80.4% at Anping, Chiating and Tungkang, respectively. The highest lethal potency of a gastropod specimen was 1900 mouse units (MU). The specimens collected from Tungkang showed the highest frequency of toxic specimens and toxicity, followed by those from Chiating and Anping. The specimens collected in autumn and spring showed higher toxicity than those collected in other seasons. Moreover, another 17 specimens of N. clathrata were collected for testing the toxin secretion by electric shock treatment. It is found that the gastropod did not secrete any additional toxin when electric shock treatment was performed twice at approximately 1-hr intervals. The toxicity of secreted toxin was 206 MU. PMID- 1440625 TI - Hepatic glutathione concentrations and the release of pyrrolic metabolites of the pyrrolizidine alkaloid, monocrotaline, from the isolated perfused liver. AB - We have examined the relationship between the metabolism of the pyrrolizidine alkaloid, monocrotaline, and glutathione concentration in the isolated, perfused rat liver. On perfusion of monocrotaline (300 microM) through the isolated liver, high concentrations (1.1 mM) of its metabolite glutathionyldehydroretronecine are released into bile, while much lower amounts (4.86 microM; 0.05 mumol/g liver) accumulate in the perfusate over a 1 hr perfusion period. Metabolite concentration in both the bile and perfusate increase when the level of monocrotaline perfused is increased to 900 microM. Metabolite release is also elevated in livers pretreated with phenobarbital. Monocrotaline perfusion lowered glutathione concentrations in the liver from 30 min onwards. Livers from animals treated with buthionine sulfoximine or chloroethanol showed much lower glutathione levels after 60 min perfusion. Livers from chloroethanol-treated (but not buthionine sulfoximine-treated) animals showed significantly lower release of pyrroles into the bile on perfusion with monocrotaline, but there is no effect on the rate of build-up of pyrrolic metabolites in the perfusate. We conclude that hepatic glutathione concentrations and the release of pyrrolic metabolites of monocrotaline mutually interact. Exposure of the liver to monocrotaline reduces glutathione concentrations, while marked depletion of liver glutathione concentration leads to a decrease in the release of monocrotaline metabolites. PMID- 1440626 TI - Effects induced by bothropstoxin, a component from Bothrops jararacussu snake venom, on mouse and chick muscle preparations. AB - Bothropstoxin, a 13,700 mol. wt myotoxic phospholipase homologue isolated from the venom of Bothrops jararacussu and devoid of PLA2, proteolytic or hemolytic activities, inhibited muscle twitch tension, evoked either directly or indirectly through stimulation of the motor nerve in the mouse phrenic-diaphragm preparations. The compound action potential of the muscle was also abolished with a similar time course. In addition, the toxin (0.7 mM) evoked membrane depolarization which was inhibited in the presence of 10 mM Ca2+. In chick biventer cervicis muscle, the toxin (2 mM) induced a contracture that reached its maximum amplitude in 44.8 +/- 15.6 min (n = 6) and was not blocked by either d tubocurarine or tetrodotoxin. The time to maximum amplitude was reduced to 5.5 +/ 1.0 min (n = 4) in nominally Ca(2+)-free Krebs solution and was completely abolished in Ca(2+)-free Krebs solution containing 1 mM EGTA. PMID- 1440627 TI - Antivenom and biological effects of ar-turmerone isolated from Curcuma longa (Zingiberaceae) AB - A potent antivenom against snakebite was isolated from Curcuma longa, a plant commonly used in traditional Brazilian medicine. The fraction consisting of ar turmerone neutralized both the hemorrhagic activity present in Bothrops jararaca venom, and the lethal effect of Crotalus durissus terrificus venom in mice. Immunological studies demonstrated that this fraction also inhibited the proliferation and the natural killer activity of human lymphocytes. PMID- 1440628 TI - Comparison of the potency of three Brazilian Bothrops antivenoms using in vivo rodent and in vitro assays. BIASG (Butantan Institute Antivenom Study Group). AB - Three Brazilian polyspecific Bothrops antivenoms were compared using standard W.H.O. rodent in vivo and in vitro assays of their ability to neutralize the principal venom activities of pooled whole Bothrops jararaca venom. On a volume basis, the antivenoms were equally effective in neutralizing lethal activity in mice, and there were only minor differences in their ability to neutralize venom induced haemorrhage, necrosis and procoagulant activity. Antivenom efficacy in neutralizing defibrinogenation varied. However, when equal amounts of antivenom IgG were compared, it was found that the FUNED antivenom best neutralized lethality, haemorrhage, necrosis and fibrinogen clotting activity. Vital Brazil and FUNED antivenoms were equally effective in neutralizing plasma coagulant activity but Vital Brazil antivenom was the more effective in neutralizing defibrinogenation. PMID- 1440629 TI - Citrate is an endogenous inhibitor of snake venom enzymes by metal-ion chelation. AB - Citrate levels in selected snake venoms were determined by an enzymatic assay coupled to NADP+ reduction. Citrate concentrations in different viper venoms (n = 5) varied from 95 to 150 mM, in crotalids (n = 3) from 63 to 142 mM, and in elapids (n = 4) from 17 to 163 mM. In Bothrops asper venom Ca(2+)-ion concentrations varied from 2.5 to 3.6 mM, suggesting that the high relative citrate levels may serve to chelate endogenous divalent metal cations, thereby inactivating divalent cation requiring enzymes. Control experiments with B. asper phospholipase A2 MIII in the presence of 2.5 mM Ca2+, showed that the enzyme is completely inhibited by 20 mM citrate. Crotalus adamanteus 5'-nucleotidase and phosphodiesterase are also inhibited 100 and 75%, respectively, by 100 mM citrate. By forming complexes with divalent metal ions, citrate markedly reduces the activities of selected enzymes in snake venoms. Secretion of high concentrations of citrate may represent an important mechanism by which snakes protect themselves against the toxic effects of their own venoms. PMID- 1440630 TI - Effects of sand viper (Cerastes cerastes) venom on isolated smooth muscle and heart and on haematological and cardiovascular parameters in the guinea-pig. AB - The effects of the venom of the sand viper (Cerastes cerastes) on haematological and cardiovascular parameters and on isolated ileum, trachea, pulmonary artery and atrium from the guinea-pig were studied. In concentrations from 0.2 micrograms/ml to 0.6 mg/ml, snake venom caused concentration-dependent relaxation of the longitudinal ileal segments and the epinephrine-precontracted pulmonary artery rings, increased the tone of the tracheal rings and increased the rate of the spontaneously beating atrium but depressed the amplitude of its contraction. Low doses (0.04-0.4 mg) of the venom caused transient small depression of both heart rate and contractility of the isolated perfused heart. A higher dose (1.0 mg) significantly inhibited both parameters and delayed their recovery. An i.v. injection of 0.12 mg/kg of the snake venom to anaesthetized guinea-pigs had no effect on red blood cell count, haemoglobin concentration or the haematocrit value but significantly reduced the circulating white blood cells, the plasma clotting time and erythrocyte deformability. Also, i.v. injections of 0.02-0.2 mg/kg of the venom caused initial depression of the systolic and the diastolic blood pressure followed by complete or partial recovery and subsequent hypotension. These observations indicate that C. cerastes venom has multiple sites of action which may help in better understanding the pathology of bites by this snake. PMID- 1440631 TI - Cardiovascular effects of Acanthaster planci venom in the rat: possible involvement of PAF in its hypotensive effect. AB - Cardiovascular effects of the crowns-of-thorns starfish (Acanthaster planci) venom were examined in rats. The crude venom extracted from the spines of A. planci caused systemic hypotension associated with an increase in heart rate and a decrease in renal cortical blood flow when given i.v. The hypotensive effect of the venom was not inhibited by pretreatment with atropine, indomethacin or aprotinin, but was significantly inhibited by SRI 63-441, a platelet activating factor (PAF) antagonist. The venom caused dose-dependent vasorelaxation of the isolated rat aortic ring preparation precontracted by noradrenaline, an effect which was significantly attenuated by pretreatment with SRI 63-441, methylene blue or parabromophenacyl bromide. Denudation of the endothelium also diminished the vasorelaxing effect of the venom. Both the vasorelaxing and the hypotensive effects showed tachyphylaxis. These results suggest the release of PAF or a PAF like substance from the endothelium by the venom. PMID- 1440632 TI - The toxicity of macrocyclic trichothecenes administered directly into the rat brain. AB - The tested macrocyclic trichothecenes are produced by Myrothecium fungi and by the plant Baccharis megapotamica. The toxicity of five macrocyclic trichothecenes has been measured by intracerebral and subcutaneous injection into rats. It is assumed that the toxic effects are based on inhibition of protein synthesis. Intoxication of rats by these compounds finds expression in slowly progressing respiratory depression and paralysis of skeletal muscles. The macrocyclics are derived from verrucarol, which lacks ring D and exhibits only low toxicity. The high toxicity of the macrocyclics, established by intracerebral and subcutaneous applications, may thus be attributed to the presence of the large ring D. PMID- 1440633 TI - Occurrence of the mycotoxin chlamydosporol in Fusarium species. AB - The mycotoxin chlamydosporol (C11H14O5) has been independently isolated from three different Fusarium species (F. chlamydosporum, F. acuminatum and F. culmorum), suggesting that its distribution may be widespread. We have developed a sensitive, specific fluorometric assay for chlamydosporol that allows quantitation in crude culture extracts. Using this assay we have observed production of chlamydosporol on rice medium by 23 of 40 isolates (58%) of Fusarium sp. examined in amounts as high as 0.8% (wt/wt) dried culture medium. PMID- 1440634 TI - Experimental myonecrosis induced by the venoms of South American Micrurus (coral snakes). AB - Venoms from 11 taxa of Micrurus (coral snakes) from Brazil and Colombia were tested for myotoxic activity in mice. All venoms, except that of M. surinamensis, induced myotoxicity as judged by the increase in plasma creatine kinase levels and by histological analysis. Qualitatively, these venoms induced a similar necrotic pattern, although there were conspicuous quantitative differences between them. PMID- 1440635 TI - European viper venoms: haemorrhagic and myotoxic activities. AB - Thirty-one venom samples from European vipers (genera Vipera and Daboia) were tested for haemorrhagic and myotoxic activity by intramuscular injection into mice. Most venoms exhibited haemorrhagic activity and fewer had myotoxic activity, both of which are not strictly related. PMID- 1440636 TI - Microcystin-like toxins in different freshwater species of Oscillatoria. AB - In January and September of 1989 and March 1990 blooms of Oscillatoria rubescens, Oscillatoria tenuis and Oscillatoria mougetii were found in Lake Simbirizzi and Lake Flumendosa in Sardinia, and in Lake San Puoto in the Lazio region of Italy. By using different extraction methods and HPLC analysis, two microcystin-like toxins (RR-like and YR-like), similar to some of the toxic compounds produced by the Cyanophycea Microcystis aeruginosa, were detected in these blooms. PMID- 1440637 TI - Bibliography of toxinology. PMID- 1440638 TI - Comparison of the purity and efficacy of affinity purified avian antivenoms with commercial equine crotalid antivenoms. AB - Antivenoms were raised in laying hens by repeated immunizations with detoxified crotalid snake venoms and purified from egg yolks by affinity chromatography. While the affinity purified avian antivenoms were essentially pure IgG, commercial equine (Wyeth) and W.H.O. international reference antivenoms (Trimeresurus flavoviridis) contained several non-immunoglobulin contaminants. In standard mouse protection assays, the purified avian Crotalus atrox and T. flavoviridis antivenoms were 6.3 and 2.0 times as potent, respectively, as these equine antivenoms in neutralizing venom lethality. The purity, efficacy, and ease of manufacture of avian antivenoms, and their inability to fix mammalian complement, make them an attractive alternative to equine and other mammalian antivenoms. PMID- 1440639 TI - Molecular properties and structure-function relationships of lethal peptides from venom of Wagler's pit viper, Trimeresurus wagleri. AB - Two new lethal peptides (waglerins) were purified from the venom of Trimeresurus wagleri, and sequenced. We found them to be analogs of lethal peptides (waglerins) I and II reported previously (Weinstein et al., Toxicon 29, 227-236, 1991), with an additional Ser-Leu on the amino terminus. Three of the four waglerins were synthesized and the products were chemically and biologically equivalent to the naturally occurring counterparts in venom. Murine i.p. LD50 for synthetic waglerins I, SL-I and II were 0.33, 0.22, and 0.51 mg/kg, respectively. The single, intramolecular disulfide bond in each synthetic peptide formed rapidly in high yield. The reduced (cysteine-containing) forms of the peptides appeared to have significant toxicities, even without prior disulfide bond formation, but synthetic analogs with serine substituted for cysteine were not toxic. The synthetic dimer of waglerin I, formed by two intermolecular disulfide bonds, was not toxic, but rapidly rearranged to lethal, monomeric waglerin I at alkaline pH upon the addition of 5 mM beta-mercaptoethanol. Waglerin I was inactivated by cleavage at Tyr-15 with chymotrypsin. PMID- 1440640 TI - Separation of insecticidal components from an extract of the roots of male Piper guineense (west African black pepper) by gas chromatography. AB - A petroleum ether extract of Piper guineense male roots showed insecticidal activity when tested against Musca domestica. Gas chromatography of the extract yielded four active fractions, one of which was a pure component which was identified by spectral and chemical methods as pellitorine (N-isobutyl-2E,4E decadienamide). The root extract lost about half of its insecticidal potency during passage down the GLC column, and much of the residual activity was due to the presence of pellitorine. It was concluded that GLC facilitates the isolation of active components in a pure form, but causes some insecticidal components of the root extract to be lost. PMID- 1440641 TI - Identification of insecticidal peptides from venom of the trap-door spider, Aptostichus schlingeri (Ctenizidae). AB - Nine insecticidal peptides were isolated from the venom of the trap-door spider, Aptostichus schlingeri. Seven of these toxins cause flaccid paralysis of insect larvae within 10 min of injection and all were lethal within 24 hr. The complete amino acid sequences (32-76 residues) of six peptides are presented. The identified peptides contain three or four disulfide bonds and the larger peptides (74-76 residues) are quite similar in sequence with carboxyl termini as free acids, not amidated. PMID- 1440642 TI - Neuromuscular effects of four phospholipases A2 from the venom of Pseudechis australis, the Australian king brown snake. AB - Four homologous single chain phospholipases A2 (Pa-1G, Pa-5, Pa-12C and Pa-15) were tested for neuromuscular effects on chick biventer cervicis and mouse hemidiaphragm nerve-muscle preparations. The four isozymes blocked directly elicited (mouse hemidiaphragm) and indirectly elicited (mouse and chick nerve muscle preparations) twitch responses in concentrations of 1-30 micrograms/ml. The order of potency seen in both types of preparations was Pa-1G = Pa-5 greater than Pa-12C much greater than Pa-15. All four isozymes caused slow-onset, sustained contractures and reduction of muscle membrane potentials. In the chick preparation, responses to acetylcholine, carbachol and KCl were reduced by exposure to the toxins. It is concluded that the toxins act primarily postsynaptically to depress muscle contractility, perhaps by directly damaging muscle fibres. The order of potency agrees with their phospholipase A2 activity. Pa-1G is unusual because it is an acidic molecule, most toxic phospholipases being basic. PMID- 1440643 TI - Potential-dependent alpha-latrotoxin interaction with black lipid membranes. AB - The influence of membrane potential on alpha-latrotoxin insertion into bilayer lipid membranes (BLM) has been investigated. It was found that positive potentials cis to toxin application stimulated the formation of channels in the bilayer. A two-step model of latrotoxin/membrane interaction is put forward to explain these data. In the first step, latrotoxin irreversibly binds to the bilayer without forming conductive structures. The second step of the process represents rapid insertion of the protein molecule into the bilayer with the formation of the conducting channel. We imagine the driving force for this process to be the interaction of charged groups in the toxin molecule with the electric field applied across the BLM. Our results are compared with known data on the interaction of LTX with synaptosomal membranes. PMID- 1440644 TI - Activation of bovine factor V by an activator purified from the venom of Naja naja oxiana. AB - The crude venom of many elapid snakes appeared to contain proteins that activated blood coagulation factor V. The factor V activator present in the venom of Naja naja oxiana was purified to homogeneity by chromatography on a mono-S column. The activator was a single chain protein with an apparent mol. wt of 48,000, as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and by gel permeation chromatography on Sephacryl S200. Activation of bovine factor V by the purified venom activator was accompanied by proteolytic cleavage of factor V and resulted in the formation of two major polypeptide chains with mol. wts of about 90,000 and 77,000. The final product obtained was compared with thrombin-activated factor V for its ability to function as cofactor in factor Xa-catalysed prothrombin activation in the presence of negatively charged phospholipid vesicles (5 mole% phosphatidylserine/95 mole% phosphatidylcholine). The Km for prothrombin obtained at a saturating amount of venom-activated factor Va was nine-fold higher than with thrombin-activated factor V (0.83 microM vs 0.09 microM, respectively) whereas both factor Va molecules stimulated the Vmax of thrombin formation some 6000-fold. Both forms of factor Va promoted the binding factor Xa to negatively charged phospholipid vesicles. However, the apparent Kd for factor Xa was less favorable in the presence of venom-activated factor V (0.67 x 10(-9) M) than in the presence of thrombin-activated factor V (0.043 x 10(-9) M). Thrombin cleaved a peptide bond in the 77,000 mol. wt polypeptide chain of venom-activated factor V, which resulted in the formation of a normal factor Va light chain. This peptide bond cleavage was, however, not associated with a change of cofactor activity. Venom treatment of thrombin-activated factor V, on the other hand, did remove a small fragment (mol. wt approximately 4000) from the heavy chain of factor Va (94,000), yielding a molecule with reduced cofactor activity. The diminished cofactor activity of venom-activated factor V is, therefore, likely due to the fact that a small peptide fragment, involved in the interaction with prothrombin and factor Xa, is missing from the heavy chain of venom-activated factor V. PMID- 1440645 TI - Pharmacological studies of jumper ant (Myrmecia pilosula) venom: evidence for the presence of histamine, and haemolytic and eicosanoid-releasing factors. AB - Jumper ant venom was prepared by extraction of venom sacs in distilled water and centrifugation to remove insoluble material. Jumper ant venom (2 micrograms/ml) produced a biphasic response on isolated guinea-pig ileum, i.e. an initial rapid contraction followed by a slower prolonged contraction. The histamine antagonist mepyramine (0.1 microM) inhibited the first phase of this response by greater than 90%. In the isolated rat stomach fundus strip (which is insensitive to histamine), jumper ant venom (6 micrograms/ml) produced only a single contraction. No tachyphylaxis was observed to repeated doses of jumper ant venom in guinea-pig ileum or rat fundus strip. Responses to jumper ant venom of the egg albumin-sensitised guinea-pig ileum were not significantly different before and after an in vitro anaphylactic response induced by egg albumin (0.5 mg/ml). Fluorometric assay revealed a mean value of 0.9 +/- 0.2% of the dry weight as histamine in jumper ant venom. Both the lipoxygenase/cyclo-oxygenase inhibitor BW755C and the cyclooxygenase inhibitor indomethacin significantly inhibited the second phase response to jumper ant venom of the guinea-pig ileum, and the response of the rat fundus strip. The muscarinic receptor antagonist atropine (0.1 microM), the bradykinin antagonist [Thi5,8,D-Phe7]-bradykinin (10 microM) and the angiotensin converting enzyme inhibitor captopril (20 microM) did not affect either phase of the venom response in guinea-pig ileum. Jumper ant venom caused haemolysis of guinea-pig blood. The degree of haemolysis was significantly reduced when boiled venom was used. These results suggest that jumper ant venom contains histamine and may cause the release of cyclo-oxygenase products. It also contains a heat-sensitive haemolytic factor. PMID- 1440646 TI - Structure determination and toxicity of a new microcystin from Microcystis aeruginosa strain 205. AB - A new hepatotoxic microcystin was isolated from the cyanobacterium Microcystis aeruginosa strain 205. Its structure was found to be [Dha7]microcystin-RR as determined by amino acid analysis, mass spectrometry and 1H NMR spectroscopy. LD50 value (i.p. mouse) of this toxin was 180 micrograms/kg. The 48 hr lethal concentration (48-hr-LC50) of the toxin for larvae of the yellow fever mosquito, Aedes aegypti, was 14.9 micrograms/ml. PMID- 1440647 TI - Pathological and biochemical changes induced in mice after intramuscular injection of venom from newborn specimens of the snake Bothrops asper (Terciopelo). AB - Venom from newborn Bothrops asper snakes has higher lethal, hemorrhagic, edema forming, proteolytic and defibrinating activities than venom from adult B. asper specimens. Electrophoretic analysis confirmed the variation between these venoms. Intramuscular injection of 100 micrograms of venom from newborn specimens in mice induced defibrination, together with moderate increments of serum levels of lactate dehydrogenase, creatine kinase, hemoglobin and total proteins. A conspicuous hemorrhage developed in injected muscle rapidly after envenomation, probably due to a drastic alteration in capillaries and larger blood vessels. Other histological alterations included moderate myonecrosis, lung collapse and prominent renal damage, characterized by tubular necrosis and hyalinization. Polyvalent antivenom effectively neutralized lethal, hemorrhagic and indirect hemolytic activities of newborn B. asper venom, although requiring higher antivenom doses than neutralization of venom from adult B. asper. PMID- 1440648 TI - Precursor structure of omega-conotoxin GVIA determined from a cDNA clone. AB - The Ca2+ channel blocking neurotoxin, omega-conotoxin GVIA, is a 27-amino acid peptide with three disulfide bonds. We have determined the precursor structure of this peptide by analyzing a cDNA clone obtained from a Conus geographus venom duct library. The omega-conotoxin GVIA prepropeptide is 73 amino acids in length comprising a 22 amino acid signal sequence, an intervening region of 23 amino acids, and finally, a 27 amino acid toxin region. A C-terminal glycine residue is later processed to a C-terminal amide moiety. The omega-conotoxin GVIA precursor exhibits regions of strong homology to the previously characterized King-Kong peptide precursor, but shows surprising divergence as well. The possible significance of the precursor organization is discussed. PMID- 1440649 TI - IgG antibodies to Loxosceles sp. spider venom in human envenoming. AB - The presence and specificity of IgG antibodies produced by patients with loxoscelism were studied. The loxoscelism diagnosis was supported mainly by clinical parameters. A search for IgG antibodies anti-Loxosceles gaucho venom in patients with loxoscelism submitted to serumtherapy showed antibodies in four out of 20 patients. The IgG antibodies were detected as early as 9 days and as late as 120 days after bite. The highest IgG antibody titer was 1:640 and the lowest was 1:80. Immunoblotting tests showed that human anti-L. gaucho IgG antibodies recognize preferentially the components responsible for the dermonecrotic and lethal activities of the venom. A comparison of the clinical picture, the level of serum IgG antibodies and the dose of antivenom administered suggest that there is no relationship between these parameters. PMID- 1440650 TI - Histopathological changes in WEHI-3B leukemia cells following intoxication by cytotoxin P4 from Naja nigricollis nigricollis venom. AB - The histopathological changes in WEHI-3B leukemia cells were followed by light and electronmicroscopy at different time intervals following exposure to cytotoxin P4 from Naja nigricollis nigricollis venom. At 1 hr after exposure to the toxin (2.5 x 10(-7) M) deformation was detected, primarily in the mitochondria, followed by vacuolization in the cytoplasm and an increase in lysosome number at 2 hr post-intoxication. Thereafter, the endoplasmic reticulum assumed a microsomal-like appearance, the plasma membrane was disrupted and, finally, the cells released their content to the culture medium. It is postulated that cytotoxin P4 may affect mitochondria either indirectly, by stimulating intracellular processes after binding to the cell membrane, or directly by interaction with the mitochondria after penetrating into the cell. PMID- 1440651 TI - Bibliography of toxinology. PMID- 1440652 TI - Characterization of snake venom components acting on blood coagulation and platelet function. AB - Snake venoms can affect blood coagulation and platelet function in various ways. The physicochemical properties and the mechanisms of actions of the snake venom components affecting blood coagulation and platelet function are discussed. PMID- 1440653 TI - Cross-reacting antigens in the butter clam (Saxidoma giganteus) and their relationship to total paralytic shellfish poison toxicity. AB - A specific protein with an apparent mol. wt of 23,000 was identified in foot homogenate derived from paralytic shellfish poisoning (PSP) contaminated butter clams and was found to cross-react with crab-saxitoxin-induced protein (SIP) antiserum. Antiserum, once cross-absorbed against non-toxic shellfish material, was incubated with tissue homogenate derived from 52 butter clams with varying total PSP toxicities in a prototype ELISA. A significant (r = 0.83; P less than 0.001) correlation existed between soluble clam antigen content in foot homogenate and total PSP toxicity; the latter measured by the mouse lethality bioassay. From the ELISA results, a soluble antigen threshold of 0.1% total protein was successfully used to distinguish between PSP toxic and non-toxic butter clams. It is proposed that this type of screening assay could be used in conjunction with the standard mouse bioassay to increase PSP monitoring and potentially reduce unnecessary animal testing. PMID- 1440654 TI - Ricin-induced hepatic lipid peroxidation, glutathione depletion, and DNA single strand breaks in mice. AB - The ability of ricin, the glycoprotein toxin from the castor bean (Ricinus communis), to stimulate oxidative stress was investigated. Following the i.p. administration of 25 micrograms ricin/kg or the vehicle to female CF-1 mice, the effects of ricin on hepatic lipid peroxidation, nonprotein sulfhydryl (reduced glutathione) content and DNA single-strand breaks were determined at 0, 12, 24, 36, 48 and 72 hr post-treatment. Hepatic lipid peroxidation significantly increased 3.4-, 3.8-, and 3.0-fold relative to control values at 24, 36, and 48 hr post-treatment, respectively. Hepatic nonprotein sulfhydryl concentrations decreased significantly to approximately 51%, 61% and 65% of control values, at 24, 36, and 48 hr, respectively. The incidence of hepatic DNA single-strand breaks increased by 2.9-, 2.8-, and 2.4-fold relative to the zero time values at 24, 36, and 48 hr after treatment with ricin, respectively. No significant differences were observed in either lipid peroxidation or nonprotein sulfhydryl concentrations at 12 or 27 hr post-treatment. Decreases in liver and intestinal weight to body weight ratios were observed in ricin-treated animals, while no changes were observed in spleen and kidney weight to body weight ratios. These results indicate that in the liver of mice, ricin induces an oxidative stress which is maximal at approximately 36 hr post-treatment. PMID- 1440655 TI - Purification and characterization of an antithrombin III inactivating enzyme from the venom of the African night adder (Causus rhombeatus). AB - A serine proteinase was isolated from the venom of the night adder (Causus rhombeatus) by fast protein liquid chromatography (anion-exchange, gel filtration and hydrophobic interaction). The protein (termed CR-serpinase) had an estimated mol. wt of 45,500 as determined by SDS-PAGE, pI of 4.7 and a carbohydrate content of 18.9%. Incubation of CR-serpinase with purified human antithrombin III at a molar ratio of 1:66 resulted in a loss of more than 90% of the initial AT III activity within 10 min. The reaction was dependent on heparin. In SDS-PAGE inactivation of human antithrombin III was correlated with the occurrence of two cleavage products. The cleavage site in the antithrombin III molecule was determined to be Arg 393-Ser 394 by amino-terminal sequencing. CR-Serpinase had no thrombin-like activity since no fibrinogen conversion was induced and had no procoagulant activity. CR-Serpinase activity was not inhibited by antithrombin III-heparin and was not decreased by a 10-min preincubation in normal human plasma. Inactivation of antithrombin III by CR-serpinase appeared to be very specific. PMID- 1440656 TI - Influence of unilateral ovarian torsion to the contralateral ovary. AB - An experimental study was planned to show the suppression of contralateral ovary in unilateral ovarian torsions. In the study, 55 New Zealand female rabbits were used. Basal and stimulation 17 beta estradiol values were measured and unilateral torsion in 20 rabbits, bilateral torsion in ten rabbits and bilateral oophorectomy in five rabbits were performed. Eight, 16, 24 hours after the procedure, 17 beta estradiol levels were measured again and the second stimulation values maintained. The control group consisted of 20 rabbits. Values were analyzed statistically and the results were significant. PMID- 1440657 TI - Effects of endurance training under hyperoxia on serum and tissue lipid levels in rats. AB - Effects of 6 weeks endurance training (5 days per week) under hyperoxia (60% O2 plus 40% N2) on serum and tissue lipid levels were investigated in male rats. Rats were divided into 4 groups: normoxia-control (NC), hyperoxia-control (HC), normoxia-training (NT), and hyperoxia-training (HT). NT and HT groups were run on a treadmill in a chamber at 20 m per min with a 6 degree gradient for 30 min. The chamber was perfused with hyperoxic gas. After training under hyperoxia, high density lipoprotein cholesterol (HDL-C) was higher (p less than 0.01) than in the normoxic condition, but there were no changes in serum lipids and glucose, or liver and aorta cholesterol. Skeletal muscle TG and liver glycogen in hyperoxic condition tended to show the higher values. Basal lipolysis of adipose tissue was increased (p less than 0.05) by hyperoxia, and decreased (p less than 0.01) by training, but there was no change of norepinephrine induced lipolysis in any group. The results suggest that endurance training or resting under hyperoxia induces increased HDL-C or lipolytic activity of adipose tissue. These effects might be caused by greater fat oxidation during exercising or resting under hyperoxia. PMID- 1440658 TI - Progressive facial hemiatrophy with localized scleroderma. AB - A 46-year-old woman who presented with progressive facial hemiatrophy (PFH) following localized scleroderma is described. The patient had a markedly deformed and depressed plaque surrounded by erythema on the right cheek. She also showed linear scleroderma with hair loss on the occipital area and morphea lesions on the neck and shoulder. Histological findings of the facial and other atrophic lesions were consistent with localized scleroderma. Therefore, the PFH and localized scleroderma may have had the same pathological background in this case. PMID- 1440659 TI - Cardiac tamponade in the blastic crisis of chronic myelogenous leukemia. AB - A 36-year-old man with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) developed hemorrhagic pericarditis with tamponade as a terminal manifestation of the blastic crisis. Cardiac tamponade should be kept in mind as an uncommon cause of death of CML patients. Based on a literature review, symptomatic pericarditis in patients with CML blast crisis suggests imminent death. This is in contrast to long-term survival for patients in the chronic phase. PMID- 1440660 TI - Plasmapheresis in the Tokai University Medical Center, 1983-1989. AB - There were 634 instances of plasmapheresis performed on 152 patients in the Kidney Center, Tokai University Hospital, in the seven year period from Jan. 1983 to Dec. 1989. The average number of plasmapheresis treatments per patient was highest for those with neurological and dermatological disease (6.7), followed by liver disease (5.6), and drug intoxication (1.2). The major treatment modalities for the liver, collagen, drug intoxication, hematologic, neurologic and hyperlipidemic disorders were plasma exchange (PE) and double filter plasmapheresis (DFPP). Recently, however, the use of plasma perfusion (PP) and immunoadsorbent plasma perfusion (IPP) has been increasing because of their ability to selectively adsorb various pathologic macromolecules. PMID- 1440661 TI - [The morphofunctional characteristics of the dystrophic and reparative processes in experimental autodermoplasty using a CO2 laser]. AB - The aim of this work was research of the morphofunctional features of rabbit free skin flaps after CO2 laser and scalpel interventions. pO2, histologic and histochemical data were analyzed. The results evidence an insignificant delay of the pO2 growth in laser-treated flaps early after surgery. This fact hints at a low speed of laser-treated flaps vascularization because of wound coagulation necrosis. However, this does not influence the course of the reparative process. Our conclusions are confirmed by histologic and histochemical findings. PMID- 1440662 TI - [A clinico-morphological evaluation of the effect of antiseptics on the degree of root canal cleaning and the potentials for its improvement]. PMID- 1440663 TI - [A temperature assessment of the treatment of exacerbated chronic periodontitis with the immobilized proteinase preparation profezim]. AB - Presents the results of studies of the gingival thermal response in patients with chronic periodontitis exacerbations. Profezyme, an immobilized proteinase enzyme, was used in the treatment of 51 patients (test group) and chymotrypsin was administered to 43 controls. Anti-inflammatory action of profezyme was demonstrated. Reduction of the gingival temperature and pain alleviation evidence a high efficacy of the drug. PMID- 1440664 TI - [The results of the clinical use of the immobilized-protease enzyme profezim in treating exacerbated chronic periodontitis]. AB - The authors characterize the action of profezyme, an immobilized proteinase enzyme, used in the treatment of patients with exacerbations of chronic periodontitis. Time course of symptomatology was followed up in 65 patients in various periods of periodontitis therapy. Prolonged enzymic therapy helped reduce the length of treatment by 2-3 times. PMID- 1440665 TI - [The efficacy of clinical indices in determining periodontal status]. AB - The accuracy and reproducibility of a number of clinical indices used in assessment of the status of periodontal tissues was evaluated in clinical examinations of 240 students. The Green-Vermillion index and the CDL periodontal index were found the most accurate and reproducible, their efficacies ranging within 86-97%. PMID- 1440666 TI - [The microbial status of the periodontal pocket]. AB - Analysis of components helped reveal the true relationships between the counts of individual representatives of the bacterial association in the contents of 18 periodontal pouches. Though the authors did their best to select a group of patients with the periodontitis course as similar as possible, the multidimensional grouping method has demonstrated the heterogeneity of this group. Four types of periodontal pouches were distinguished, differing by their bacterial status; this probably requires a differentiated approach to its correction. PMID- 1440667 TI - [A comparative study of the efficacy of the action of a number of local antimicrobial preparations on the species and quantitative composition of the microbial flora in periodontal pockets]. AB - The effects of a number of antibiotics were studied with the use of phase contrast microscopy. The time course of the qualitative and quantitative changes of the periodontal pouch microflora evidences that a mixture of trichopol with chlorohexidine is the most effective therapy for periodontal pouch sanitization. PMID- 1440668 TI - [The morphofunctional characteristics of the free cells and microvessels of the gingiva in inflammatory periodontal diseases]. AB - A comprehensive assessment of the gingival histohematic barrier components in patients with gingivitis and periodontitis was carried out. Analysis of the intratissular correlations has led the authors to a hypothesis on the presence of a peculiar 'break-off' of the interstructural relationships determined by the severity of the periodontal injury. Gingivitis is characterized by a change, though minimal, of correlations, as against the intact periodontium. Involvement of the entire tissue complex of the periodontium in the process is associated with elevation of the counts of both positive and negative relationships between free stromal cells. Accumulation of free stromal cells and disorder of their cooperation is parallel with lowering of alkaline phosphatase activity and isolation of polymorphonuclear leukocytes, this forming the structural basis for the progress of the inflammatory dystrophic process in the periodontium. PMID- 1440669 TI - [Indices characterizing the expression of hyperesthesia of the hard dental tissues in patients with periodontitis]. AB - Clinical examinations of 226 patients with periodontitis have revealed in 61% of them hyperesthesia of the hard dental tissues, that was mostly generalized, characterized by a marked reaction to thermal, chemical, and tactile stimulants. Study of the mineral metabolism has demonstrated that growing bone tissue loss in dental biopsy specimens and gingival fluid is associated with reducing levels of P, Ca, and Mg. Combination of clinical manifestations of periodontitis and hyperesthesia necessitate search for combined therapy aimed at simultaneous elimination of hyperesthesia and inflammation. PMID- 1440670 TI - [A morphological assessment of the efficacy of the deaggregation therapy of chronic catarrhal gingivitis]. AB - Light optics, electron microscopy, morphometry were used to study the structural changes in the epithelial cells and endotheliocytes of gingival papillary capillaries of patients with chronic catarrhal gingivitis after papaverin therapy. The studies have revealed signs of disappearance of intercellular edema and a higher degree of cellular differentiation; signs of normalization of transcellular fluid transport were seen in the endotheliocytes, and aggregations of formed elements of the blood disappeared. PMID- 1440671 TI - [Ways to improve the treatment of patients with phlegmons of the maxillofacial area]. AB - The examination has involved a total of 216 patients (111 in the study group and 105 in the reference one) with maxillofacial phlegmons. Patients of the main group were administered multiple-modality treatment with surgical treatment of the purulent focus, involving a primary suture on the wound and intraarterial local drug therapy. Partial necrectomy was found possible in the majority of cases with the surgical treatment of the purulent focus; therefore to prevent dissemination of the inflammatory process and liquidate it as soon as possible surgery had to be performed against the background of the maximal permissible antibiotic concentration in the adjacent tissues. Primary suturing of the purulent wound had to be combined with draining and continuous dialysis of the postoperative wound. The postoperative wound healed by primary tension in 91.89% of patients in the main group; the incidence of complications was lower in them than in the reference group; the length of hospital stay and invalidity periods were reduced almost twofold. PMID- 1440672 TI - [Lipid peroxidation in suppurative-inflammatory diseases of the maxillofacial area]. AB - The levels of lipid peroxidation products were measured in patients with various pyoinflammatory conditions of the maxillofacial area: abscess, phlegmons, chronic mandibular osteomyelitis). Blood plasma and red cell levels of lipoperoxides were found increased and alpha-tocopherol levels lowered in all the examinees. PMID- 1440673 TI - [The clinico-immunological aspects of dental implantology]. AB - Analyzes the clinical and immunologic data evidencing that implantation, as a rule, induces immunologic shifts in patient's body. Traces the direct relationship between the frequency and severity of complications and the type of the patient's immune response to implantation, the intensity of this response being directly related to the implantation material and volume. Basing on the relationship between the clinical and immunologic data, recommends examination of the patients' immune status for the prediction of the results of the surgical stage of dental implantation and for the assessment of new implantation material intended for introduction into practical dentistry. PMID- 1440674 TI - [The bone tissue of the jaws in congenital and acquired deformities]. AB - Biophysical parameters of the jam bones were examined in patients with congenital and acquired deformations. Ash content, density, mineral content, and microhardness were estimated in 58 patients aged 17 to 28. The mean values of these characteristics were found to be unrelated to the individual features and the type of the changes in the bone tissue, associated with deformations of the jaws. Frequency ranging of the individual values helped obtain a more objective picture of the bone tissue status. Bone tissue density was found increased in congenital maxillary and mandibular deformations. These data evidence a lowered plasticity of the bone tissue in the patients with congenital deformations of the jaw bones. PMID- 1440675 TI - [The regional blood circulation of the parotid gland and the correction of its disorders in chronic interstitial parotitis]. AB - Elevated vascular tone, lengthened time of intraglandular arterial bed filling, fibrinogenemia, elevated plasma tolerance to heparin were detected in 32 patients with chronic interstitial parotitis (CIP) during exacerbation and in a number of CIP patients with the remission of the disease. Correction of microcirculation disturbances is advisable during CIP exacerbation; in remission it may be effective in patients with the late stage of parotitis, in those with parotitis coursing along with diabetes mellitus, essential hypertension, or against the background of prolonged oral drug therapy (e. g. clofelin). Drugs correcting the microcirculatory disorders are conducive to a sooner alleviation of the inflammation and better and longer preservation of the function of the parotid glands. PMID- 1440676 TI - [Body immunological reactivity in patients with chronic nontumorous diseases of the parotid salivary glands]. AB - Examinations of 81 patients and 30 healthy donors have revealed a variety of immunologic disturbances in different forms of chronic nontumorous conditions of the parotid glands. Lymphocyte sensitization to salivary gland antigens was observed in all the patients, but was the most marked in those with Sjogren's disease. The studies permit considering the detected shifts in the immunity system an important component of the pathogenesis of chronic nontumorous diseases of the parotid glands. These findings may be useful in the differential diagnosis, prognosis, and adequate therapy of salivary gland diseases. PMID- 1440677 TI - [The regional blood circulation in the parotid gland area in Sjogren's disease (syndrome)]. AB - Rheographic investigations of the parotid gland area in 103 patients with Sjogren's disease (syndrome) that developed in the presence of chronic nonspecific sialadenitis during its various stages and inflammation phases have demonstrated that the blood stream volumic rate directly depended on the inflammation phase and intensity of this phase. During remission the circulation in the salivary glands was close to normal. PMID- 1440678 TI - [The dynamics of fracture healing in the bones of the zygoma area]. AB - Investigation of the reparative histogenesis in patients with zygomatic bone fractures suffered in different periods in the past included histologic study of the tissue specimens taken from fracture sites during surgical intervention, studies of the osteogenesis, topographic-anatomic position of bone fragments, their mobility and configuration, and clinical and pathomorphologic changes in the soft tissues adjacent to the fracture site. Specific features of the reparative osteogenesis of the facial skull flat bones and changes in the soft tissues adjacent to the fracture site were detected. PMID- 1440679 TI - [The late results of observing and treating patients with histiocytosis X and involvement of the jaw bones]. AB - Eighty-one patients with histiocytosis X involving the jaw bones were followed up for 30 years; the patients presented with involvement of the lungs, skin, mucosa, other bones of the skeleton, and diabetes insipidus signs. In 58 of the 81 patients eosinophilic granuloma eventuated in a generalized process: chronic xanthomatosis or Hand-Schuller-Christian's disease. This fact permits a conclusion that eosinophilic granuloma is an initial stage of the same systemic disease, histiocytosis X, and that subdivision of histiocytosis X into 3 forms, accepted in literature, is undesirable, for it erroneously presents the essence of the process. Therapeutic recommendations are given. PMID- 1440680 TI - [The importance of the surgical treatment method in cancer of the oral mucosa with the primary tumor 4 cm in size and larger]. AB - The authors analyze the results of surgical treatment of patients with local disseminated squamous-cell carcinoma of the buccal mucosa. The data on the survival rate of patients treated with different surgical methods are presented and variants of combined operations described. PMID- 1440681 TI - [A method for performing stimulation electromyography of the masticatory muscles in man]. AB - A principal block scheme of an apparatus complex is suggested and a method for examination of masticatory muscle function is described. The method is based on electrostimulation of masticatory nerve followed by registration and analysis of the masticatory muscle action evoked potentials. The block scheme of the apparatus complex includes a universal electrostimulator ESU-2. Examinations of 30 healthy volunteers and 30 patients with unilateral fractures of the mandible helped define the major parameters of stimulation electromyography. The patients were treated by splints applied on the teeth with fixation on both jaws. By day 28 of the investigation the M-response amplitude dropped more than twofold and its length by 1.5 times as against the mean parameters in health. PMID- 1440682 TI - [The modelling of mandibular osteomyelitis]. AB - The method suggested by the authors permits a reliable reproduction of mandibular osteomyelitis in white rats. The primary localization and pattern of the infectious process in this model well correspond to odontogenic osteomyelitis, this permitting a preclinical study of new drugs and physiotherapeutic methods intended for patients with odontogenic diseases. PMID- 1440683 TI - [The experience of using the 1-day hospital in maxillofacial surgery]. AB - The authors describe for the first time the experience gained by a one-day hospital for oral surgery. The efficacy of this hospital is analyzed and economic effect estimated. PMID- 1440684 TI - [The characteristics of treating odontogenic osteomyelitis against a background of malaria in the population of the Republic of Burundi]. AB - All the patients were administered preoperative antimalarial therapy, antibiotics and sulfanilamides, and agents maintaining the defense factors, as well as detoxifying and desensitizing therapy. Rational nutrition was prescribed. All these measures helped liquidate the inflammation foci not only in the bones, but in the soft tissues of the paramaxillary area as well. PMID- 1440685 TI - [An x-ray method for determining the position of the tongue in the oral cavity]. AB - The suggested modified technique for assessing the tongue position in the oral cavity is based on teleroentgenography in the lateral projection and estimation of cephalometric parameters. Theoretical rationale is given for the use of skeletal check points in the mandibular area and cervical portion of the spine and of the mandibular and spinal reference lines. Indications for the use of this method are defined and its advantages described. PMID- 1440686 TI - [The comparative characteristics of mastication tests]. AB - Changes in the values of Manly's [correction of Manley's], Rubinov's, and the author's mastication tests were studied in subjects with intact dentition, orthognathic occlusion; the tests were carried out 3 times each with intervals of 2-3 weeks. Correlations of the data of Dahlberg's [correction of Dalberg's], Manley's, Rubinov's and the author's tests were studied and the pattern of changes in the data of the tests in minor dentition defects analyzed. Repeated tests yielded better results; the data of various tests were found incompatible; the suggested test was found the most sensitive and accurate. The basic requirements to a mastication test are formulated. PMID- 1440687 TI - [The clinical evaluation of the use of metal ceramic dentures with a Simet glass ceramic coating]. AB - Good results of clinical follow-up of patients with cermet dentures coated with cimet (glass ceramic) permit recommending this type of coating for wide practical use. Reconstructive prosthetics with glass ceramic and metal and cermet dentures should involve denture modeling in the articulator and a prophylactic check-up at least once a year with oral hygiene and functional occlusion control. PMID- 1440688 TI - [A method for the functional forming of the distal section of a complete upper denture]. PMID- 1440689 TI - [An automated system for the collection and processing of clinico-diagnostic information in developing methods for treating dental defects by using dental implants]. AB - A dialogue medical information system "Dental Implant" is described, intended for the collection and analysis of clinico-diagnostic information with the aim of developing methods for the treatment of patients with dentition defects, making use of dental implants. This automated system permits a rapid and effective analysis of surgical and orthodontic complications and is intended for operation by a non-programmer. PMID- 1440690 TI - [Kalipsol-based balanced intravenous anesthesia in pediatric outpatient dental practice]. AB - Basing on clinical studies of anesthesia in 568 children, central hemodynamic studies, analysis of the blood acid-base balance and gases, glycemia level, and assessment of the psychoneurologic status, the authors validate the usefulness of calypsol-based anesthesia in practical outpatient pedodontics. Such anesthesia did not influence the stability of central hemodynamics parameters, nor did it change the acid-base balance and blood sugar level; it provided an adequate protection of the patient from surgical stress with the adaptation mechanisms remaining intact. The child may leave the clinic 2.5-3 h after the intervention and a test for adequate adaptation to the environment. Calypsol-based balanced anesthesia improves outpatient care of the children, introduction of this method into practice will bring about a good economic effect. PMID- 1440691 TI - [A comparative study of the role of atresia and stenosis of the outflow duct of a salivary gland in the pathogenesis of dystrophic and inflammatory changes]. AB - Experiments were carried out with submandibular salivary glands of 20 dogs. Complete obturation of the submandibular duct (in 10 animals) was achieved by binding this duct. Partial impairment of the saliva flow from the gland was induced in 10 animals by fixing a metal ring on the duct. The experiment has demonstrated that both complete and partial obturation of the salivary duct result in the development of chronic sialadenitis. Partial obturation of salivary outflow from the gland did not result in an acute inflammation but in a flaccid process, slowly developing dystrophic changes in acinar cells, gradually developing sclerosis of the glandular parenchyma and stroma. These data indicate a direct relationship between the intensity of dystrophic changes in the salivary gland and the severity of impairment of salivary discharge. PMID- 1440692 TI - [The characteristics of the occlusal surface relief of the molars and its role in caries susceptibility in Nenets children]. AB - Analysis of the principal odontological and odontogliphic parameters of 1088 molars of caries-susceptible and caries-resistant Russian and Nenets children has demonstrated that molar caries-resistance of the Nenets children is explained by the prevalence of the basic and supplementary grooves and elements that create a more intricate fissure pattern, the tooth size, groove length, number of tubers and fossae at the site of fissure fusion. PMID- 1440693 TI - [Changes in the oral cavity of children as possible diagnostic signs of leukemia]. AB - In 15 of the 65 children the initial signs of leukemia coincided with oral diseases running an uncommon course: acute or chronic recurrent herpetic stomatitis, periostitis, parotitis. An infectious process showing no tendency to resolution, stubborn infiltration of tissues in inflamed foci, hemorrhages, and changed total status of a child may be regarded as probable diagnostic signs of leukemia, requiring a profound examination, carried out by a dentist and hematologist. PMID- 1440694 TI - [The morphological parameters of the dental arches in children with unilateral complete cleft lip and palate]. AB - The size and proportions of dentitions and relationships between longitudinal, transverse, and vertical parameters of the upper and lower dentitions and palatine processes were examined in 42 children (22 girls and 20 boys), aged 5-6 years, with unilateral complete labiopalatine clefts before uranoplasty. Analysis of correlations in the findings was carried out and 12 reliable coefficients of correlations obtained. PMID- 1440695 TI - Minor and trace sterols in marine invertebrates 65. 23-Epidihydrocalysterol: a new cyclopropane-containing sponge sterol. AB - A new cyclopropane-containing sterol was isolated from the marine sponge Cribrochalina vasculum. The new sterol was characterized by nuclear magnetic resonance and mass spectrometry and the structure was shown to be (23R,24S,28R) dihydrocalysterol. Implications concerning the biosynthesis of cyclopropane and cyclopropene sterols in sponges are discussed. PMID- 1440696 TI - Persistent estrogen responsiveness of ras oncogene-transformed mouse mammary epithelial cells. AB - Ovarian steroids are associated with the proliferation of normal as well as tumorigenically transformed mammary epithelial cells. The experiments performed in this study were designed to establish that (1) tumorigenic transformation induced by the ras oncogene is associated with alterations in estradiol biotransformation, (2) altered endocrine responsiveness persists in the fully transformed tumor cell phenotype and (3) specific perturbations induced by the ras oncogene can be experimentally downregulated. The ras transfectant pH06T and the tumor-derived T1/Pr1 cells exhibited 3- and 43-fold increases, respectively, in C-16 alpha hydroxylation of estradiol relative to the parental mouse mammary epithelial cells (P less than 0.0001). At the cellular level, this alteration corresponded with approximately 90-fold increase in the anchorage-independent growth of T1/Pr1 cells (P less than 0.0001). Estrogen responsiveness of T1/Pr1 cells was demonstrated by their suppression of growth in phenol red-free and/or tamoxifen-supplemented medium and by the reversal of antiproliferative effect of tamoxifen by phenol red and estradiol. Indole-3-carbinol, a naturally occurring tumor suppressive agent, was able to upregulate C-2 hydroxylation at the expense of C-16 alpha hydroxylation of estradiol. Treatment of T1/Pr1 cells with indole-3 carbinol resulted in a substantial decrease in anchorage-independent growth. PMID- 1440697 TI - The effect of dihydrotestosterone and culture conditions on proliferation of the human prostatic cancer cell line LNCaP. AB - Cell density, nutritional state, and serum factors modify the growth response of LNCaP human prostatic cancer cells to dihydrotestosterone. Evaluation of growth response to dihydrotestosterone requires logarithmic transformation of cell count or thymidine incorporation data. Under conditions of dose response, growth increases with cell density but no significant interaction of dihydrotestosterone with cell density was found under optimal culture conditions. The frequency of media change was a significant factor in modulating dose response. When cells from cultures maintained at different feeding periods were plated at different cell densities of (trypan blue) viable cells, significant effects of plating density on dihydrotestosterone response were found. Dihydrotestosterone protects cells under the adverse effects of media deprivation. Under the extreme adverse effects of serum deprivation, cells respond to dihydrotestosterone even under conditions of increasing cell loss. The effects of dihydrotestosterone on final cell density were significant. In the absence of serum, the elongated cells of LNCaP assume a round shape, but many remain adherent to the culture dish and can be restored to normal morphology by serum. A number of growth factors fail to restore normal morphology that was completely restored by a combination of fibronectin and dihydrotestosterone. We have not developed a practicable serum free system for LNCaP. PMID- 1440698 TI - Steroid metabolism in teleost gonads: purification and identification of metabolites by high-performance liquid chromatography. AB - A simple, efficient, and comprehensive technique for the purification, identification, and quantitation of the common steroid metabolites synthesized by the gonads of teleosts involving five systems of high-performance liquid chromatography (HPLC) was developed. Steroid standards were identified in HPLC by UV absorption at 254 nm or 280 nm, by differential refractive index, or by using radioactive standards. Metabolites that do not absorb UV light and are not resolved in the isocratic HPLC systems were identified in thin-layer chromatography following purification by HPLC. By using this technique, most of the steroid metabolites, including some polar metabolites, synthesized by the gonadal tissues of the teleosts can be purified within three steps of chromatography. The HPLC systems reported here are also useful in identifying the chromium trioxide oxidized products of metabolites, such as triols and tetrols, which considerably narrows down the number of probable metabolites. PMID- 1440699 TI - A highly specific heterologous enzyme-linked immunosorbent assay for measuring testosterone in plasma using antibody-coated immunoassay plates or polypropylene tubes. AB - A highly specific and sensitive enzyme-linked immunosorbent assay, using a heterologous combination of antiserum raised against testosterone-3-(O carboxymethyl) oxime-bovine serum albumin and penicillinase-labeled testosterone 11 beta-carboxymethyl ether, was developed for measuring testosterone in human plasma. Immunoassay plates (96 wells) provided a sensitivity of 2.5 pg/well. This was achieved by maintaining the molar ratios of steroid to enzyme between 10 and 20. The assay was very specific for testosterone and did not show any cross reaction with the related C19 steroids tested. Replacement of immunoassay plates with the locally available polypropylene tubes raised the detection limits to 25 pg/tube, but improved the range of doses of testosterone that could be measured up to 10,000 pg. The antiserum to testosterone derivative was linked to both immunoassay plates and polypropylene tubes through immunochemical bridges. Comparison of testosterone values of 52 plasma specimens obtained by both solid phase methods with those of radioimmunoassay showed good correlation. PMID- 1440700 TI - Comparison of estrogen sulfotransferase and pregnenolone sulfotransferase of guinea pig. AB - Guinea pig adrenal estrogen sulfotransferase from either sex was eluted as a single peak, irrespective of buffer salt concentration, when subjected to fast protein liquid chromatography on gel filtration columns. The same enzyme was consistently eluted in two distinct peaks during chromatofocusing. Adrenal pregnenolone sulfotransferase was eluted during gel filtration in a heterogeneous pattern, dependent on salt concentration. These properties have made possible almost complete separation of the two sulfotransferases in one step, although adrenal estrogen sulfotransferase may possess a minute intrinsic ability to catalyze sulfation of pregnenolone. Pregnenolone sulfotransferase had no measurable activity toward estrone. Pregnenolone sulfotransferase from both sexes yielded variable elution patterns during chromatofocusing. Estrogen sulfotransferase from the adrenal, as well as that of guinea pig chorion, was strongly inhibited by N-ethylmaleimide and to a lesser degree by iodoacetamide and iodoacetate. Adrenal and chorion estrogen sulfotransferases were thermolabile and were activated, although not protected from the effect of heat, by binding to 3'-phosphoadenosine 5'-phosphosulfate. Adrenal pregnenolone sulfotransferase was inhibited only by high concentrations of N-ethylmaleimide and not at all by iodoacetamide or iodoacetate. It was more thermostable than the estrogen sulfotransferase and was not activated by binding to 3'-phosphoadenosine 5' phosphosulfate. PMID- 1440701 TI - Secular trends in stroke incidence and mortality. The Framingham Study. AB - BACKGROUND: The reduction in US stroke mortality has been attributed to declining stroke incidence. However, evidence is accumulating of a trend in declining stroke severity. METHODS: We examined secular trends in stroke incidence, prevalence, and fatality in Framingham Study subjects aged 55-64 years in three successive decades beginning in 1953, 1963, and 1973. RESULTS: No significant decline in overall stroke and transient ischemic attack incidence or prevalence occurred. In women, but not men, incidence of completed ischemic stroke declined significantly. Stroke severity, however, decreased significantly over time. Stroke with severe neurological deficit decreased in later decades, with a fall in rates of severe stroke cases in which patients were unconscious on admission to the hospital. There was no substantial change in the case mix of infarcts and hemorrhages and no decline in hemorrhage to account for the decline in severity. The proportion of isolated transient ischemic attacks increased significantly over the 30 years studied, yielding an apparent and significant decline in case fatality rates in men only. CONCLUSIONS: Secular trends in stroke incidence and fatality did not follow a clear or definite pattern of decline. While a significant decline in stroke severity occurred over three decades, incidence of infarction fell only in women. The decline in total case fatality rates occurred only in men and resulted largely from an increased incidence of isolated transient ischemic attacks. The severity of completed stroke was significantly lower in the later decades under study. PMID- 1440703 TI - Cerebral cysticercosis as a risk factor for stroke in young and middle-aged people. AB - BACKGROUND AND PURPOSE: A probable association between cerebral cysticercosis and susceptibility to stroke, especially among young and middle-aged patients, has been reported. We examined the association between cerebral cysticercosis and stroke and the possible factors causing this association. METHODS: In 169 stroke patients (75 males and 94 females) under 65 years of age admitted to our neurology department, we evaluated the following possible risk factors: arterial hypertension, diabetes, cardiac disease, hyperlipidemia, smoking, alcohol abuse, and cerebral cysticercosis. In 169 control patients under 65 years of age matched by sex and age, we evaluated the same possible risk factors for stroke. RESULTS: In the univariate matched analyses, the frequencies of cerebral cysticercosis (p < 0.001), arterial hypertension (p < 0.001), cardiac disease (p < 0.001), hyperlipidemia (p < 0.05), and alcohol abuse (p = 0.05) were higher in the stroke patients than in the control patients. After controlling for possible confounding factors, we found that arterial hypertension (p < 0.001), cardiac disease (p < 0.001), and cerebral cysticercosis (p < 0.001) were independent risk factors for stroke. CONCLUSIONS: Cerebral cysticercosis should be considered a risk factor for stroke in young and middle-aged individuals. PMID- 1440702 TI - Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism. AB - BACKGROUND AND PURPOSE: The role of lipoprotein abnormalities in the development of ischemic cerebrovascular disease has not been sufficiently clarified. The aim of this study was to identify the lipoprotein profile in ischemic cerebrovascular disease and the possible role of apolipoprotein E polymorphism. METHODS: The relation between the concentrations of lipoprotein(a), intermediate density lipoproteins, apolipoprotein A-I, apolipoprotein B, apolipoprotein E, and other lipoproteins was studied in 100 men with ischemic cerebrovascular disease (48 atherothrombotic, 28 lacunar, and 24 of unknown type) and in 100 healthy age matched men as a control group. RESULTS: Patients with ischemic cerebrovascular disease had significantly higher levels of lipoprotein(a), lipids carried by intermediate density lipoproteins, and low density lipoprotein cholesterol and lower levels of high density lipoproteins than control subjects. Patients with atherothrombotic infarction had higher total serum cholesterol and low density lipoprotein cholesterol concentrations than patients with lacunar infarction. To assess lipoprotein abnormalities in normolipidemic subjects, a subgroup of 38 patients with ischemic cerebrovascular disease and 53 control subjects, both with serum cholesterol levels < 5.2 mmol/l (200 mg/dl) and triglycerides < 2.3 mmol/l (200 mg/dl), was analyzed. Serum lipoprotein(a), lipids carried by very low density lipoproteins and intermediate density lipoproteins, and low density lipoprotein triglycerides were significantly higher in normolipidemic patients compared with normolipidemic control subjects, whereas high density lipoprotein cholesterol levels were lower. Apolipoprotein E polymorphism in our ischemic cerebrovascular patients differed from that of the control group, with the epsilon 4 allele being more prevalent. CONCLUSIONS: Increased serum lipoprotein(a) levels and intermediate density lipoprotein abnormalities together with decreased high density lipoprotein levels are major risk factors for ischemic cerebrovascular disease, even in normocholesterolemic and normotriglyceridemic subjects. Finally, the epsilon 4 allele could probably be a predisposing genetic marker for ischemic cerebrovascular disease. PMID- 1440704 TI - Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study. AB - BACKGROUND AND PURPOSE: The early time course after acute stroke of cerebral N acetylaspartate, creatine and phosphocreatine, and compounds containing choline was studied in vivo by means of localized water-suppressed proton magnetic resonance spectroscopy. METHODS: Eight patients with acute stroke were studied serially in the acute phase, 1 week after, and 2-4 weeks after the onset of clinical symptoms. Ten healthy volunteers served as controls. A stimulated echo (STEAM) sequence was used for measurement of the brain metabolites in a volume of interest located within the infarcted area as visualized by magnetic resonance imaging. For quantification, the unsaturated water signal was used as the internal standard. Regional cerebral blood flow in the infarcted area was measured relative to a symmetrically located unaffected area by means of single photon emission computed tomographic scanning, using 99mTc-labeled d,l hexamethylenepropyleneamine oxime as the flow tracer. RESULTS: Relative regional cerebral blood flow was considerably reduced in the infarcted area in the acute phase. After 1 week, hyperemia was seen in all but one patient. The N acetylaspartate content was significantly reduced, with the loss appearing to occur between 6 and 24 hours after the stroke incident. The reduction in N acetylaspartate content was greater in the central part than in the peripheral part of the infarcted area. Creatine and phosphocreatine were also reduced in the infarcted area, whereas no significant change was seen in the choline content. CONCLUSIONS: Assuming that N-acetylaspartate content reflects neuronal survival or loss, our results may suggest that treatment procedures with restoration of blood flow to severely ischemic areas should be initiated within the first 6 hours after stroke onset. PMID- 1440705 TI - Imaging of the intracranial vertebrobasilar system using color-coded ultrasound. AB - BACKGROUND: Anatomic variety and difficult accessibility of the vertebrobasilar arteries pose considerable problems to conventional ultrasound. We evaluated the diagnostic potential of transcranial color-coded sonography in the distal part of this system. METHODS: We insonated the intracranial section of the vertebrobasilar arteries through the foramen magnum window in 24 healthy individuals using a Doppler color flow imaging system in connection with a 2.5 MHz sector transducer. Magnetic resonance images in special inclination planes were performed and compared with the color-coded duplex images in five cases. RESULTS: The B-mode image of the craniocervical junction and the intracranial parenchymal structures in addition to the color-coded blood flow allowed an unambiguous identification of the vertebrobasilar arteries (vertebral artery, 96%; basilar artery, 79%; and posterior inferior cerebellar artery, 50%). Blood flow velocities were measured considering the insonation angles: vertebral arteries, 50/24 cm/sec (30 degrees); basilar artery, 59/28 cm/sec (4 degrees); and posterior inferior cerebellar artery, 56/30 cm/sec (20 degrees) [peak systolic/end diastolic blood flow velocity (mean angle correction)]. CONCLUSIONS: Transcranial color-coded sonography enables accurate identification and differentiation of the intracranial vertebrobasilar arteries and improves accuracy of Doppler measurements. It may prove useful for evaluation of tortuosity and for hemodynamic studies in this vascular territory. PMID- 1440706 TI - Risks and benefits of shunting in carotid endarterectomy. The International Transcranial Doppler Collaborators. AB - BACKGROUND AND PURPOSE: Controversy continues about the pathogenesis of perioperative stroke in carotid endarterectomy and the use of shunting. The purpose of this study was to determine, using transcranial Doppler ultrasonography, the severity of ischemia during clamping of the carotid artery as a basis for analysis of complications in patients operated on with and without shunting. METHODS: In a retrospective study, 11 centers contributed 1,495 carotid endarterectomies monitored with transcranial Doppler. The cases were divided into groups with severe, mild, and no ischemia, and each group was subdivided according to shunt use. The perioperative rate of severe stroke attributable to intraoperative ischemia, in addition to total perioperative stroke, was determined for each subgroup. RESULTS: Severe ischemia occurred in 7.2% of our cases but cleared spontaneously in about half of these. In those with persisting ischemia the rate of severe stroke was very high, while shunting protected against stroke in such cases. If ischemia did not occur, the stroke rate was higher with shunting, although not so high as in unshunted cases with severe ischemia. Slightly more than one third of the severe strokes were due to postoperative cerebral hemorrhage or carotid thrombosis, unrelated to clamp induced ischemia or shunting. CONCLUSIONS: Carotid endarterectomy complications might be reduced by selectively shunting only for severe persisting ischemia. Monitoring of cerebral ischemia would be essential to selective shunting. PMID- 1440707 TI - Prediction of cerebral ischemia by ophthalmoscopy after carotid occlusion in gerbils. AB - BACKGROUND AND PURPOSE: The Mongolian gerbil provides a unique model of unilateral focal cerebral ischemia because of the lack of posterior communicating arteries in all gerbils as well as an absence of an anterior communicating artery in approximately 20% of the gerbil population. It is unclear how to identify unequivocably the subpopulation of animals that would suffer a severe focal cerebral ischemia after unilateral carotid occlusion. METHODS: Ninety-three male gerbils were exposed to unilateral occlusion of the right common carotid artery. The severity of neuronal loss was evaluated histologically in gerbils selected as having significant focal ischemia based on either behavioral criteria (i.e., the demonstration of stereotypical behavior within 1 hour after occlusion) or ophthalmoscopic criteria (i.e., interruption of the retinal arterial perfusion within 10 minutes of carotid ligation as assessed with an ophthalmoscope). After 3 hours of unilateral carotid occlusion, cerebral blood flow was reinstated for 24 hours before fixation for histological analysis. The viability of the CA1 region of the hippocampus, lateral cortex, and medial cortex was scored on a scale of 0-4 based on the percentage of apparent neuronal loss (e.g., 0, no damage; 4, > 75% damage (the Viability Index). RESULTS: Twenty-eight percent of the gerbils met the behavioral selection criteria, and 17% met the ophthalmoscopic criteria. In the specimens selected by behavioral criteria (n = 7), 30% demonstrated no evidence of postischemic neuronal loss; the mean +/- SEM Viability Index scores for CA1, lateral cortex, and medial cortex were 1.6 +/- 0.6, 1.0 +/- 0.3, and 0.3 +/- 0.2, respectively. Of the animals selected by ophthalmoscopic criteria (n = 12), 100% had severe ischemic tissue damage to the ipsilateral hemisphere; the Viability Index scores for CA1, lateral cortex, and medial cortex were 3.5 +/- 0.1, 3.1 +/- 0.2, and 1.2 +/- 0.2, respectively; all scores were significantly larger than those observed in the behaviorally selected group. CONCLUSIONS: Selection of animals by ophthalmoscopic criteria provides a reliable, consistent method to predict animals with severe focal cerebral ischemia. PMID- 1440708 TI - Diffusion-weighted imaging studies of cerebral ischemia in gerbils. Potential relevance to energy failure. AB - BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging has been shown to be particularly suited to the study of the acute phase of cerebral ischemia in animal models. The studies reported in this paper were undertaken to determine whether this technique is sensitive to the known ischemic thresholds for cerebral tissue energy failure and disturbance of membrane ion gradients. METHODS: Diffusion-weighted images of the gerbil brain were acquired under two sets of experimental conditions: as a function of cerebral blood flow after controlled graded occlusion of the common carotid arteries (partial ischemia), as a function of time following complete bilateral carotid artery occlusion (severe global ischemia), and on deocclusion after 60 minutes of ischemia. RESULTS: During partial cerebral ischemia, the diffusion-weighted images remained unchanged until the cerebral blood flow was reduced to 15-20 ml.100 g-1.min-1 and below, when image intensity increased as the cerebral blood flow was lowered further. This is similar to the critical flow threshold for maintenance of tissue high-energy metabolites and ion homeostasis. After the onset of severe global cerebral ischemia, diffusion-weighted image intensity increased gradually after a delay of approximately 2.5 minutes, consistent with complete loss of tissue adenosine triphosphate and with the time course of increase in extracellular potassium. This hyperintensity decreased on deocclusion following 60 minutes of ischemia. CONCLUSIONS: The data suggest that diffusion-weighted imaging is sensitive to the disruption of tissue energy metabolism or a consequence of this disruption. This raises the possibility of imaging energy failure noninvasively. In humans, this could have potential in visualizing brain regions where energy metabolism is impaired, particularly during the acute phase following stroke. PMID- 1440709 TI - Cerebral vasoconstriction in response to hypocapnia is maintained after ischemia/reperfusion injury in newborn pigs. AB - BACKGROUND AND PURPOSE: Hypocapnic cerebral vasoconstriction is used therapeutically to reduce elevated intracranial pressure caused by cerebral edema. Because cerebral ischemia/reperfusion injury causes a selective loss of prostanoid-dependent responses, including vasodilation to hypercapnia, we designed these experiments to examine the effect of ischemia/reperfusion on hypocapnic cerebral vasoconstriction. METHODS: Microvascular responses were studied in 10 newborn pigs (closed cranial window) in response to hyperventilation-induced hypocapnia (PaCO2, 22 +/- 2 mm Hg) both before and 45 minutes after 20 minutes of global cerebral ischemia. Responses to hypercapnia (PaCO2, 63 +/- 3 mm Hg), topical isoproterenol (10(-7) M), and norepinephrine (10(-4) M) were also studied before and after ischemia in the same animals for comparison. RESULTS: Before ischemia/reperfusion, pial arterioles vasoconstricted to hypocapnia (-17 +/- 2%) and norepinephrine (-35 +/- 4%) and vasodilated to CO2 (37 +/- 7%) and isoproterenol (25 +/- 2%). After ischemia/reperfusion, the constriction of pial arterioles to hypocapnia (-19 +/- 2%) was similar to that before ischemia. This is in contrast to the loss of dilation to hypercapnia. Dilation to isoproterenol and constriction to norepinephrine were not affected by ischemia. CONCLUSIONS: Hypocapnic cerebral vasoconstriction is maintained after ischemia/reperfusion. Since prostanoid-dependent responses, such as hypercapnic dilation, are lost following cerebral ischemia, these data suggest that hypocapnic constriction is not dependent on an intact prostanoid system and that cerebral vascular responses to CO2 involve multiple mechanisms, depending on whether CO2 is increasing or decreasing from baseline. PMID- 1440710 TI - Fructose-1,6-bisphosphate stabilizes brain intracellular calcium during hypoxia in rats. AB - BACKGROUND AND PURPOSE: Exogenously administered fructose-1,6-bisphosphate reduces neuronal injury from hypoxic or ischemic brain insults. To test the hypothesis that fructose-1,6-bisphosphate prevents changes in intracellular calcium ([Ca2+]i) and high-energy phosphate levels, we measured [Ca2+]i, intracellular pH (pHi), and adenosine triphosphate in cultured rat cortical astrocytes and cortical brain slices during hypoxia. METHODS: The fluorescent indicators fura-2 and bis-carboxyethyl-carboxyfluorescein were used to simultaneously measure [Ca2+]i and pHi with a fluorometer. RESULTS: Exposure to hypoxia (95% N2, 5% CO2) or 100 microM sodium cyanide produced transient increases in [Ca2+]i in astrocytes and sustained increases in [Ca2+]i in brain slices. Adenosine triphosphate levels fell in slices exposed to hypoxia or cyanide. Fructose-1,6-bisphosphate (3.5 mM) blocked increases in [Ca2+]i and prevented depletion of adenosine triphosphate. Fructose-1,6-bisphosphate also partially prevented adenosine triphosphate depletion in brain slices incubated in glucose-free medium. Iodoacetate (a specific inhibitor of glycolysis) elevated [Ca2+]i and partially prevented these actions of fructose-1,6-bisphosphate. Changes in pHi during hypoxia were not affected by fructose-1,6-bisphosphate. CONCLUSIONS: Fructose-1,6-bisphosphate supports adenosine triphosphate production via stimulation of glycolysis and results in the maintenance of normal [Ca2+]i during hypoxia or hypoglycemia. PMID- 1440711 TI - Effects in cats of inhibition of nitric oxide synthesis on cerebral vasodilation and endothelium-derived relaxing factor from acetylcholine. AB - BACKGROUND AND PURPOSE: We investigated the chemical identity of the endothelium derived relaxing factor generated by acetylcholine in cerebral microvessels by studying the effects and mechanism of action of inhibitors of nitric oxide synthesis from arginine on the vasodilation and endothelium-derived relaxing factor production induced by topical application of acetylcholine in cerebral arterioles. METHODS: We determined cerebral arteriolar dilation and endothelium derived relaxing factor production by bioassay in anesthetized cats equipped with cranial windows during superfusion of 10(-7) M acetylcholine before and after administration of either NG-monomethyl L-arginine or NG-nitro-L-arginine, two inhibitors of nitric oxide synthesis. RESULTS: NG-Nitro-L-arginine abolished the vasodilation from acetylcholine and eliminated the production of endothelium derived relaxing factor in the bioassay experiments. NG-Monomethyl L-arginine had no effect on the response to acetylcholine in the absence of pretreatment. However, after pretreatment with the detergent sodium dodecyl sulfate to increase cell membrane permeability, the inhibitor had effects identical to those of NG nitro-L-arginine. L-Arginine reversed the effects of the inhibitors of nitric oxide synthesis. Neither inhibitor affected baseline vascular caliber, nor did they generate a vasoconstrictor agent in the bioassay experiments. The two inhibitors of nitric oxide synthesis did not affect the response to nitroprusside or adenosine, showing that the effect on responses to acetylcholine was specific. Also, the blockade of the response to acetylcholine induced by the inhibitors of nitric oxide synthesis was unaffected by treatment with superoxide dismutase and catalase, showing that the effect was not mediated by oxygen radicals. CONCLUSION: The endothelium-derived relaxing factor generated by acetylcholine in cerebral arterioles of cats is either nitric oxide or a nitric oxide-containing substance. The effect of these inhibitors on the response to acetylcholine is mediated by inhibition of the synthesis of nitric oxide. There is no involvement of radicals, and no vasoconstrictor agent is generated. PMID- 1440712 TI - Neuroprotective effects of carvedilol, a new antihypertensive agent, in cultured rat cerebellar neurons and in gerbil global brain ischemia. AB - BACKGROUND AND PURPOSE: Free radical generation mediates part of the ischemic neuronal damage caused by the excitatory amino acid glutamate. Carvedilol, a novel multiple-action antihypertensive agent, has been shown to scavenge free radicals and inhibit lipid peroxidation in swine heart and rat brain homogenates. Therefore, we studied the neuroprotective effect of carvedilol on cultured cerebellar neurons and on CA1 hippocampal neurons of gerbils exposed to brain ischemia. METHODS: Neuroprotective mechanisms were studied using an in vitro ischemia model of cultured rat cerebellar granule cell neurons exposed to either glutamate or oxygen free radical-generating systems. Prevention of lipid peroxidation by carvedilol was studied by measuring the formation of thiobarbituric acid-reactive substance. Gerbil CA1 neuron survival was examined by direct neuronal count 7 days after 6 minutes of global ischemia with reperfusion. RESULTS: Carvedilol protected cultured neurons in a dose-dependent manner against glutamate-mediated excitotoxicity (inhibitory concentration [IC50] = 1.1 microM) as well as against a 20-minute oxidative challenge (IC50 = 5 microM). The IC50 against the oxidative challenge was lowered to 1.3 microM by growing neurons for 24 hours in the presence of carvedilol. At 10 microM carvedilol inhibited lipid peroxidation 50% and 73% (n = 4, p < 0.001) in neurons exposed to two different free radical-generating systems. Neuroprotection of 52% (n = 22, p = 0.009 versus vehicle) of gerbil CA1 hippocampal neurons was achieved by pretreatment and posttreatment with subcutaneous injection of 3 mg/kg carvedilol twice a day for 4 and 3 days, respectively. CONCLUSIONS: Carvedilol provided neuroprotection in both in vitro and in vivo models of neuroinjury, where oxygen radicals are likely to play an important role. Therefore, carvedilol may reduce the risk of cerebral ischemia and stroke by virtue of both its antihypertensive action and its antioxidative properties. PMID- 1440713 TI - Release of proinflammatory and prothrombotic mediators in the brain and peripheral circulation in spontaneously hypertensive and normotensive Wistar Kyoto rats. AB - BACKGROUND AND PURPOSE: We reported previously that stroke risk factors prepared the brain stem for the development of ischemia and hemorrhage and induced the production of tumor necrosis factor following an intrathecal injection of lipopolysaccharide, a prototypic monocyte-activating stimulus. This study evaluates whether blood or brain cells of hypertensive rats produce more proinflammatory and prothrombotic mediators than do blood or brain cells of normotensive rats. METHODS: Levels of tumor necrosis factor, platelet-activating factor, 6-ketoprostaglandin F1 alpha, and thromboxane B2 in the cerebrospinal fluid and blood of spontaneously hypertensive and normotensive Wistar-Kyoto rats were monitored before and after a challenge with lipopolysaccharide. RESULTS: Little or no activity from these mediators was found in the cerebrospinal fluid or blood of saline-injected control animals. Intravenous administration of lipopolysaccharide (0.001, 0.1, and 1.8 mg/kg) produced dose-dependent increases in blood levels of all mediators in hypertensive rats. In normotensive rats the levels were less than in hypertensive rats and were not clearly dose-related. When lipopolysaccharide was injected intracerebroventricularly, more tumor necrosis factor was measured in the cerebrospinal fluid than in the blood, suggesting local synthesis of this cytokine. Levels of tumor necrosis factor and platelet-activating factor in the cerebrospinal fluid were higher in hypertensive than in normotensive rats. The thromboxane A2/prostacyclin ratio was not altered significantly between the two rat strains. CONCLUSIONS: It is suggested that the higher incidence of brain stem ischemia and hemorrhage after the intrathecal injection of lipopolysaccharide in hypertensive rats than in normotensive rats might be related to the higher levels of the two cytotoxic factors tumor necrosis factor and platelet-activating factor produced in response to such challenge. PMID- 1440714 TI - Detection of intracranial emboli in patients with symptomatic extracranial carotid artery disease. AB - BACKGROUND AND PURPOSE: Cerebral embolism from extracranial sources is an important cause of ischemic stroke. The purpose of this limited study using long term transcranial Doppler ultrasonographic monitoring was to estimate the frequency of clinically silent intracranial embolisms in patients with symptomatic extracranial carotid artery disease. SUMMARY OF REPORT: By means of a 2-MHz pulsed-wave transcranial Doppler instrumentation, three consecutive patients with extracranial internal carotid artery stenosis (n = 2) or occlusion (n = 1) and recurrent ipsilateral ischemic events were monitored (19 hours total recording time). In addition, 10 control subjects without cerebrovascular disease were studied (25 hours total recording time). Formed-element emboli were defined as distinct signals within the fast Fourier-transform Doppler spectrum that were < 70 msec in duration and > 9dB greater in intensity than the background signal. Clinically silent formed-element embolism of ophthalmic or cerebral arteries was demonstrated in all three patients. Embolic events occurred only in the territory of the symptomatic internal carotid artery. The average rate of cerebral embolization at transcranial Doppler ultrasonography was 4.1/hr, with a mean signal duration of 47 msec. No emboli were found in control subjects. CONCLUSIONS: The observed high frequency of silent embolism of the intracranial arteries detected by transcranial Doppler monitoring in patients with recurrently symptomatic extracranial carotid artery disease should encourage studies of the prognostic and therapeutic implications of this method. PMID- 1440715 TI - Irish brogue after stroke. AB - BACKGROUND: We describe a patient who presented a unique variation of the previously described acquired foreign accent syndrome. CASE DESCRIPTION: A 65 year-old women developed an Irish brogue immediately after a deep left hemisphere stroke. The newly accented speech possibly represented a previously learned speech pattern. CONCLUSIONS: Suppressed prosodic speech patterns may reemerge in the setting of brain injury. PMID- 1440716 TI - Bilateral medial medullary infarction with oculomotor disorders. AB - BACKGROUND AND PURPOSE: We describe the first case of bilateral medial medullary infarction demonstrated by magnetic resonance imaging. We discuss the relation between this lesion and the oculomotor signs that were observed clinically. CASE DESCRIPTION: A 71-year-old man initially presented with pure motor hemiparesis, which progressed to complete quadriplegia. He also developed nearly complete vertical and horizontal ophthalmoplegia. Magnetic resonance imaging revealed upper medial medullary infarctions bilaterally that extended to the pontomedullary junction. CONCLUSIONS: We propose that the vertical oculomotor disorders resulted from involvement of the oculomotor system in the caudal brain stem, especially the caudal paramedian pontine reticular formations on both sides. PMID- 1440717 TI - The role of transesophageal echocardiography in the acute onset of paraplegia. AB - BACKGROUND AND PURPOSE: Acute paraplegia must be investigated promptly to exclude reversible causes. In this report we illustrate the usefulness of transesophageal echocardiography in identifying the vascular etiologies of acute paraplegia. CASE DESCRIPTIONS: Two patients presented with acute paraplegia, one spontaneously and the other after removal of an intra-aortic balloon pump catheter. Through the use of transesophageal echocardiography, we excluded aortic dissection and identified protruding atherosclerotic plaques in the descending thoracic aorta of each patient. Embolization of atheromatous material from the thoracic aorta was considered the most likely etiology of paraplegia in both cases. CONCLUSIONS: Embolization from atherosclerotic plaques in the thoracic aorta may be an underestimated cause of acute paraplegia. Transesophageal echocardiography provides a safe, rapid, and reliable tool for investigating a vascular etiology of acute paraplegia. PMID- 1440718 TI - Is cerebral angiography indicated in infective endocarditis? AB - BACKGROUND AND PURPOSE: Patients with infective endocarditis may develop intracranial mycotic aneurysms. Whether these patients should undergo cerebral angiography followed by prophylactic surgery if an aneurysm is detected is an unresolved question. METHODS: We estimated the probability of survival 12 weeks after the diagnosis of infective endocarditis on the basis of data available in the literature. RESULTS: For a 40-year-old female patient with right-sided hemiplegia, the 12-week survival is estimated to be 83.75% without angiography and 83.65% with angiography; the specific mortality of intracranial mycotic aneurysms is relatively small but increases by 40% (from 0.25% to 0.35%) if angiography is performed. The risk of aneurysm rupture in infective endocarditis and the mortality from rupture appear to be the most important factors that affect the analysis. CONCLUSIONS: Cerebral angiography should not be performed routinely in patients with infective endocarditis. Specific subgroups in whom such a policy might be beneficial have not yet been identified. PMID- 1440719 TI - Experimental evidence of ischemic thresholds and functional recovery. AB - BACKGROUND: Impaired blood flow below certain critical levels and an insufficient supply of energy-rich substrates cause failure of neuronal function, triggering biochemical disturbances that eventually lead to ischemic cell damage. SUMMARY OF REVIEW: This article reviews experimental studies that attempted to define those ischemic thresholds using functional and histological markers and, more recently, chemical markers of ischemic damage. CONCLUSIONS: The duration of ischemia causing irreversible cell damage still is ill defined. Reestablishment of sufficient perfusion must be induced very early after an ischemic attack to ameliorate the potentially harmful biochemical sequelae of transient ischemia. PMID- 1440720 TI - Leukoaraiosis and dementia in hypertensive patients. AB - BACKGROUND AND PURPOSE: Although our previous study demonstrated that dementia of the Binswanger type may be a disconnection dementia caused by leukoaraiosis, some hypertensive patients with marked leukoaraiosis do not develop dementia. The goal of the present study is to elucidate the pathophysiology of nondemented hypertensive patients with leukoaraiosis. METHODS: We performed clinical and neuroradiological studies, including positron emission tomography, in eight hypertensive patients with leukoaraiosis. RESULTS: Four patients were demented, and two among the other four who were not demented at the first examination developed dementia during the follow-up period. Digital subtraction angiography of the cervical and intracranial arteries demonstrated stenotic lesions in only one patient. Cerebral blood flow and oxygen metabolism in patients with dementia were markedly reduced in the white matter (59-67% of control values). In contrast, cerebral blood flow in the white matter of patients without dementia was reduced less markedly (74% of control), oxygen extraction fraction in the white matter was significantly increased (130% of control), and oxygen metabolism remained at almost-normal levels not only in the white matter but also in the cortical area. CONCLUSIONS: Hypertension-caused arteriosclerotic changes of the long penetrating medullary arteries may cause misery perfusion and later ischemic damage in the periventricular white matter. Preserved oxygen metabolism in hypertensive patients with leukoaraiosis may represent the early stage of vascular dementia of the Binswanger type. PMID- 1440721 TI - A unified form for neurological scoring of hemispheric stroke with motor impairment. PMID- 1440722 TI - Handedness and carotid plaque lesion. PMID- 1440723 TI - Use of breath holding for evaluating cerebrovascular reserve capacity. PMID- 1440724 TI - Disagreement over terms. PMID- 1440725 TI - Arrhythmias and stroke laterality. PMID- 1440726 TI - Inhibitory and enhancing activity of beta 2-glycoprotein I on antiphospholipid autoantibody binding. PMID- 1440727 TI - [The diagnosis of heart contusion in living subjects with closed chest trauma]. PMID- 1440728 TI - [The nature of the deposit of substances in gunshot injuries from a smooth-bore hunting rifle]. AB - Direct microscopic examinations of plain-barrel hunting gun-shot wounds may reveal on the victim's skin or clothes starch or paraffin particles or impressions thereof (a secondary shell trace). These data may evidence a specific charge of the cartridge and be used to specify the distance from which the shot was made, with an obligatory experimental shot made in each case. PMID- 1440729 TI - [The differential diagnosis of death from complete freezing and other causes]. PMID- 1440730 TI - [The forensic medical expertise of the victims of large-scale fires]. AB - The difficulties of present-day forensic medical expert evaluation of poisonings in fires are explained by exposure of man to highly toxic compounds that form during burning of polymers. Analyzing forensic medical expert evaluations of a large number of victims dead in a large-scale fire, the authors emphasize the necessity of measuring not only dead people's blood levels of HbCO, but of some other toxic combustion products that may exert combined effects on human body. The authors think it desirable that criteria of forensic medical evaluation of combined poisoning in fire be defined. PMID- 1440731 TI - [The use of trace deposits for establishing the weapon of an injury]. AB - The author analyzes the value of traces detectable on stabbing and cutting instruments (traces of blood, isolated cells of the injured organs and tissues of human body, trace particles of textile fabrics) for the identification of the instrument of injury. A comprehensive assessment of the fact of detection of material traces and of the specific features of injuries of victim's body and clothes helps in some cases identify the instrument of injury. PMID- 1440732 TI - [The characteristics of conducting forensic medical expertise in cases of forcible sodomy]. PMID- 1440733 TI - [The determination of the presence of blood in the clues for material evidence]. PMID- 1440734 TI - [The combination of mixed agglutination and immunofluorescence reactions for the simultaneous detection of 2 ABO-system antigens in isolated cells]. AB - A combination of two immunologic tests, mixed agglutination and immunofluorescence, is suggested, that permits the detection of two AB0 system antigens in the same cell within one process. Such mode better validates the conclusion on the group appurtenance of cells, for instance, in analyses of mixed stains originating from different subjects with different blood groups. PMID- 1440735 TI - [The use of immunoenzyme analysis for determining ABH antigens in traces of saliva and sperm]. AB - The authors suggest a simple sensitive technique for enzyme immunoassay (EIA) of ABH antigens in saliva and semen. A two-staged dot blot solid-phase EIA on nitrocellulose membranes was employed with anti-ABH monoclonal antibodies obtained in immunization of mice with human red cells. 4-chloro-1-naphthol substrate solution was used to visualize the peroxidase label. The results of analysis of salivary and spermatic samples obtained from donors of various groups evidence that this EIA variant may be useful in forensic medicine. PMID- 1440736 TI - [The use of the orthogonal function method for calculating the background in determining ergotamine in biological material]. PMID- 1440737 TI - [The determination of phoxim in cadaveric material by gas-liquid chromatography]. AB - The developed gas-liquid chromatographic procedure for forensic chemical detection and measurement of phoxim in cadaveric material permits the detection in 25 g of an organ of 44 to 52% of added phoxim. The threshold of phoxim measurement in 100 g of the liver is 0.04 mg, the least volume of phoxim detectable being 0.02 g. The developed gas-liquid chromatographic technique should be used as an additional method together with thin-layer chromatography, for a more objective evaluation of the results of forensic chemical analysis of cadaveric material for phoxim. PMID- 1440738 TI - [Acute methanol poisonings]. PMID- 1440739 TI - [The cost price of expertise as an objective index of the work-share coefficient of the forensic medical expert]. AB - The author suggests a method for estimating the net cost of a forensic medical expert investigation, consisting in calculation of an objective real coefficient of the ratio of various expert investigations to the reference value. The ratio between forensic medical investigation budget and the total number of these investigations forms the basis for the estimation of the net cost of an expert evaluation. PMID- 1440740 TI - [The use of intravital tooth staining in personal identification]. PMID- 1440741 TI - [The possibilities for using computer technology and programmed systems in forensic medicine]. PMID- 1440742 TI - [The choice of the control object in the forensic medical determination of the intravital origin of mechanical injuries]. PMID- 1440743 TI - Presuicide attempt communications between parasuicides and consulted caregivers. AB - A high percentage of parasuicides visit professional caregivers prior to the attempted suicide. The content or outcome of these consultations is unknown. We interviewed hospitalized attempters and the professional caregivers they identified as having been consulted prior to their attempts. About half of these patients directly disclosed suicidal symptoms or intentions, especially to mental health professionals. These professionals more often inquired about suicidal ideations than did nonpsychiatric physicians. However, few caregivers noted suicidal thinking or probed suicidal symptoms. The data suggest that professional caregivers and especially nonpsychiatric physicians should be more sensitive and responsive to the signs and symptoms of suicidality. PMID- 1440744 TI - Intensive follow-up does not decrease the risk of repeat suicide attempts. AB - We carried out a randomized controlled trial to determine whether an intensive intervention after a suicide attempt could decrease by half the risk of a repeat attempt in the following two years. After initial assessment and randomization, experimental subjects attended 18 therapy appointments over one year, including one home visit, and measures to improve attendance. Control subjects received the usual care. Of 63 experimental subjects, 35% made a repeat attempt, and so did 30% of 63 control subjects. The study had a 99% power to detect the desired decrease of risk (30% to 15%). Clearly, the intervention did not achieve its objective. PMID- 1440745 TI - Adolescents' experience with and response to suicidal peers. AB - The present study investigated a sample of 325 suburban high school students' knowledge of suicidal peers, whether they had ever talked to a suicidal peer, and, if so, what they actually did in that situation. Sixty-eight percent of the females and 42.5% of the males reported knowing a teen who had committed or attempted suicide. Ninety-seven students reported having talked to a peer who was definitely considering suicide; of these, 63% talked to their peer about his or her concerns, 24.7% told an adult, and 12% did nothing in response to the encounter. Ninth graders were significantly more likely to do nothing as compared to eleventh graders. A mixed pattern of results was found as to the relationship of the response of youth to suicidal peers and their general experience with suicidal peers. The results confirm the importance of adolescents themselves for the prevention of youth suicide, and the need to convince adolescents to report at-risk peers to an adult. PMID- 1440746 TI - Older adults: the next suicide epidemic? AB - Suicide rates historically and currently are highest by age among those over the age of 65. Predictions of markedly higher rates for future older adults have been advanced. Possible alternative factors that might produce lower risk among future elderly Americans are presented and it is argued that future trends are uncertain. Predictions of elderly suicide are made based on an assumption of stable rather than changing rates. Constant rates produce estimates of more than twice the current number of suicides and a proportionate increase in the number of suicides from one in five for the 1980s to one in three by the year 2030. The elderly are and likely will be a group with high suicide risk. Immediate efforts to lower elderly suicide risk and avert high future rates are recommended. PMID- 1440747 TI - Self-directed and other-directed aggressive behavior in a forensic sample. AB - Fifty habitually aggressive men were assessed for self-directed aggressive behavior (SDAB) and other-directed aggressive behavior (QDAB). Subjects displaying SDAB were compared with subjects exhibiting exclusively ODAB. The former were found to engage in more frequent acts of verbal aggression, physical aggression against objects, and physical aggression against others, as well as in more severe acts of verbal aggression and physical aggression against others. They were also more likely to receive diagnoses of mental retardation, organic personality disorder, intermittent explosive disorder, or autism. Findings are consistent with the presence of a neurologically based behavioral dyscontrol in the SDAB subjects. PMID- 1440748 TI - Suicide and the military justice system. AB - The United States military is sensitive to suicide. There are military policies that direct the formation of active suicide prevention programs. The U.S. military emphasizes a humanitarian approach. Modern military law, however, may view suicidal behavior as deviant. The prosecution of this behavior, although theoretically possible, has never occurred until recently. The U.S. military has now convicted soldiers for attempted suicide and assisted suicide. This article reviews these recent court decisions and suggests revisions in the military law. PMID- 1440749 TI - A suicide epidemic in a psychiatric hospital. AB - The authors report in detail on an epidemic of six inpatient suicides in a psychiatric hospital in Finland. Suggestion and identification had an effect on the timing as well as on the method of four of the suicides. The epidemic is viewed from individual, network, and organizational perspectives. The authors speculate on how such epidemics could be avoided. An increase in inpatient suicide rates has been reported from many countries, and the Werther effect may thus become a topic of considerable importance in psychiatric hospitals in the future. PMID- 1440750 TI - Gender differences in the psychosocial correlates of suicidal ideation among adolescents. AB - Gender differences in the psychosocial correlates of suicidal ideation were studied. A sample of 613 high school students (ages 14-19) completed measures of suicidal ideation, depression, hopelessness, life stress, loneliness, alcohol and drug use, and reasons for living. The results of a discriminant function analysis indicated that males reported higher loneliness and substance abuse scores than females whereas females reported greater suicidal ideation, depression, and reasons for living. The results of multiple regression analyses found that, although the same four variables, depression, hopelessness, substance abuse, and few reasons for living emerged as significant predictors of suicidal ideation in both samples, the predictive equation accounted for more of the variance in ideation scores in females (57%) than in males (46%). In a final analysis a discriminant function analysis of the subscales of the reasons for living inventory revealed that females have a greater fear of death and injury whereas males have a greater fear of social disapproval over having suicidal thoughts. This may account for the greater rate of suicide completing among males. Fear of social disapproval, more anger and impulsivity, and less help-seeking behavior among males are offered as potential variables to explain the observed gender differences. PMID- 1440751 TI - Adolescent suicide and defensive style. AB - This empirical study investigated the relation between ego defense mechanisms, diagnoses, and suicidality among 200 adolescent psychiatric patients ages 12 to 16 years. Based on a structured diagnostic interview, adolescents were divided into three groups: suicide attempters, suicidal ideators, and nonsuicidal patients. Using the Defense Mechanisms Inventory (DMI), suicidal adolescents scored higher on the defense of turning-against-self and lower on reversal, as compared to nonsuicidal adolescents. Although suicide was significantly more common among adolescents with an affective disorder, turning-against-self remained significantly associated with suicide attempt even when diagnosis was controlled for. Results demonstrate the importance of defense mechanisms in understanding adolescent suicidal behavior. PMID- 1440752 TI - A test of Durkheim's theory of suicide in primitive societies. AB - Primitive societies were classified as high, moderate, or low on independent measures of social integration and social regulation to test Durkheim's theory of suicide. The estimated frequency of suicide did not differ between those societies predicted to have high, moderate, and low suicide rates. Thus, Durkheim's theory was not confirmed. Possible reasons for these results are discussed. PMID- 1440753 TI - The suicide of Marigold Perry. PMID- 1440754 TI - [Dental care at Winterthur]. PMID- 1440756 TI - [Aging: fundamental theme in psychology?]. PMID- 1440755 TI - [Emergency service of the Winterthur Association of Dentists (VWZ). Objectives, duties and methods]. PMID- 1440757 TI - [Substitution effects in the care for the elderly in Southeast Groningen]. AB - Results are presented of a 'demonstration project' in care for the elderly in the region South-East Groningen. Three issues were at stake in this project: extension of home-care, interventions in the referral processes to nursing homes and homes for the aged and coordinated allocation and planning of services for the elderly. Effects of the intervention were assessed with a quasi-experimental control-group design. In this paper, the issue of substitution is addressed from two different angles. First, changes in utilization of services in the experimental period (1988-1990) were evaluated. Second, changes in disability of elderly clients were evaluated. In both analyses, controls for national developments took place. The analyses show that substitution occurred, both in terms of utilization of care (more home-care, less institutional care) and in terms of the levels of need of clients (increases in mean level of disability in the populations of home-care and homes for the aged). PMID- 1440758 TI - [Voting behavior of the elderly: motivation and background]. AB - On the occasion of the Dutch election for the Second Chamber of Parliament held on September 6, 1989 the Central Bureau of Statistics conducted a National Voters Survey (NKO). Voting behaviour and information about the backgrounds of this behaviour were collected among 1506 voters. A formerly developed explanatory model of party choice of the electorate also appears to apply to the 382 elderly voters (55 years and older) in the sample. The results show that party choice of elderly is mainly determined by the characteristics income, social class, religion, social values (social criticism) and opinions about politicians. The elderly differ from the younger voters (18-54 years old) on several points. For the elderly, the characteristics sex, education and social class play a more important role, whereas certain values (family values and postmaterialism) are more relevant for the 18-54 year-old group. In addition it turned out that as far as the explanation of party choice is concerned, the elderly are not a homogeneous group. Voters aged 75-plus in particular can be distinguished from the 55-64 and 65-74 year-old groups. PMID- 1440759 TI - [The elderly and memory complaints. A study of self-knowledge about memory, depression and memory abilities]. AB - A group of 24 elderly persons who applied for a memory training because of memory complaints is compared with a control group of 24 healthy persons (matched for age, sex, and education). The comparison concerned several memory tests, complaints above everyday memory, depression and aspects of meta-memory. Before training, the memory training group had more complaints about everyday memory and depression compared to the control group. The training group reported more decline in memory capacity and functioning compared to their earlier days. They also reported feelings of stress and anxiety related to memory performance in daily life. Before training, the training group had more general knowledge about basic memory processes and used memory strategies more frequently. On most memory tests no differences were found. Memory complaints of elderly people may therefore not only be related to memory abilities according to tests but also to individual (negative) beliefs in memory capacity and abilities. PMID- 1440760 TI - [Does advancing age not spoil mood?]. PMID- 1440761 TI - The Onchocerciasis Control Programme. PMID- 1440762 TI - Medicine for the tropics: past, present and future. PMID- 1440763 TI - Chloroquine-resistant Plasmodium vivax in Papua New Guinea. AB - An Australian expatriate on regular weekly antimalarial prophylaxis with chloroquine base and Maloprim developed symptomatic Plasmodium vivax infection which failed to respond adequately to 600 mg of chloroquine base. More ominously, a resident of the Highlands region of Papua New Guinea contracted vivax malaria which failed to be cleared by 2400 mg chloroquine base administered over 4 d. Both patients had achieved appropriate blood and plasma concentrations of chloroquine after treatment. Chloroquine-resistant P. vivax is now a clinical fact in Papua New Guinea. PMID- 1440764 TI - Innate resistance to new antimalarial drugs in Plasmodium falciparum from Nigeria. AB - The rapid dissemination of chloroquine-resistant Plasmodium falciparum in West Africa has been well documented and represents a significant health threat to autochthonous populations. The methodical development of alternative chemotherapeutic agents demands that dispensing new antimalarial drugs (mefloquine, halofantrine, and artemisinine [qinghaosu]) be closely monitored in order to protect their clinical utility. Indeed, mefloquine-resistant strains of P. falciparum have been reported. We present data from experiments in vitro on the innate resistance of P. falciparum isolates to mefloquine as well as a disturbing observation of transient resistance to artemisinine. The implications for the extended efficacy of these new antimalarial drugs are addressed. PMID- 1440765 TI - Plasmodium falciparum: haemoglobinase activity pattern of isolates is not related to chloroquine sensitivity. PMID- 1440766 TI - Chloroquine resistance in Plasmodium vivax: the first case in Brazil. PMID- 1440767 TI - Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria. AB - Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limiting, delayed onset cerebellar dysfunction following an attack of falciparum malaria which occurred 18-26 d previously. Concentrations of tumour necrosis factor, interleukin 6 and interleukin 2 were all significantly higher in serum samples of patients during cerebellar ataxia than in recovery sera and in the sera of 8 patients who did not develop delayed cerebellar dysfunction following an attack of falciparum malaria. Cytokine concentrations in the cerebrospinal fluid were also significantly higher in ataxic patients than in controls. These findings suggest that immunological mechanisms may play a role in delayed cerebellar dysfunction following falciparum malaria. PMID- 1440768 TI - Human cerebral malaria: alpha-galactosyl antibodies in cerebrospinal fluid. PMID- 1440769 TI - Urinary neopterin in volunteers experimentally infected with Plasmodium falciparum. AB - To investigate the kinetics of monocyte/macrophage activation in falciparum malaria we determined urinary neopterin values serially in experimentally infected volunteers. Three subjects who had been immunized with irradiated sporozoites via mosquito bites served as controls. These individuals remained aparasitaemic, afebrile and without a rise in neopterin after challenge by infective mosquitoes. Four non-immune subjects developed Plasmodium falciparum parasitaemia, fever (3 of 4) and sharp rises in neopterin. Parasite densities reached 10-100 parasitized erythrocytes per microliter before elevations in temperature or neopterin levels were detected. Onset of fever preceded the rise in neopterin excretion by one day. Prompt chemotherapy was associated with the clearance of parasites from the blood and the return of temperature and neopterin levels to normal. PMID- 1440770 TI - Urinary frequency in falciparum malaria. PMID- 1440771 TI - Detecting malaria sporozoites in live, field-collected mosquitoes. AB - A method is described for identifying malaria-infected mosquitoes, without killing them or hampering their fitness. Individual mosquitoes were induced to salivate on coverslips, and sporozoites, deposited on the glass surface, were visualized by Giemsa staining. Of 21 mosquitoes found to contain sporozoites by salivary gland dissection, 13 had delivered sporozoites on coverslips. A positive correlation was found between the amount of saliva expelled and ejection of sporozoites, indicating that the sensitivity of the method may be increased by improving the probing behaviour of the mosquitoes. The procedure described may be suitable for selecting infected mosquitoes which are able to eject sporozoites during probing. Being applicable to wild Anopheles and to large numbers of mosquitoes, the method lends itself for use in field studies on malaria. PMID- 1440772 TI - Cutaneous leishmaniasis in western Venezuela caused by infection with Leishmania venezuelensis and L. braziliensis variants. AB - Between 1975 and 1987, epidemiological studies were carried out in several rural and urban communities in the central part of western Venezuela, especially in the state of Lara. 115 positive cultures were obtained from human cases and identified by their reactivity patterns to a cross-panel of specific monoclonal antibodies using a radioimmune binding assay; 53 were Leishmania venezuelensis and 62 were L. braziliensis. Most of these stocks were also characterized by isoenzyme electrophoresis, which confirmed the identification of the L. venezuelensis isolates. The enzyme electrophoretic profiles of the L. braziliensis isolates, however, revealed two populations with distinct electromorphs, one related to the World Health Organization L. braziliensis reference strain while the other population appeared to be a hybrid between L. braziliensis and L. guyanensis. L. braziliensis variants showed the widest geographical distribution, and were found in 7 states: Districto Federal (Caracas); Lara (Barquisimeto, Crespo, Iribarren, Jimenez, Moran, Palavecino, Torres, Urdaneta); Nueva Esparta (Margarita); Portuguesa (Las Cruces, Rio Amarillo); Trujillo (Cuicas); Yaracuy (Agua Fria, Cambural, Guaremal); and Zulia (Zipa-Yare). L. venezuelensis was found in the following endemic regions: Lara (Barquisimeto, Iribarren, Jimenez, Moran); Merida (Zea); and Yaracuy (Campos Elias), showing that this parasite has a much wider geographical distribution than was initially recognized and that both these species can occur simultaneously within the same endemic region. Five isolates of L. braziliensis were made from infected donkeys (Equus asinus) in Urdaneta, Lara State, suggesting a possible domestic reservoir of L. braziliensis. PMID- 1440773 TI - Cutaneous leishmaniasis in south-western Ethiopia: Ocholo revisited. AB - The borough of Ocholo, on the western side of the Ethiopian Rift Valley, is an endemic focus for Leishmania aethiopica infection and has been surveyed thrice between 1987 and 1990. In 1989, 3022 inhabitants (> 95% of the population) were interviewed and examined. The overall prevalence of localized cutaneous leishmaniasis (LCL) was 3.6-4.0%, with a peak value of 8.5% in the 0-10 years old age group. In half of the patients the active disease was estimated to last for 9.6 +/- 6 months; in 10%, it exceeded 3 years. Scars of LCL were present in 34.3% of the residents. Leishmanin skin tests were positive in 54% of 120 school children without signs of the disease. Therefore, in Ocholo a minimum of 71.6% of the population has been exposed to L. aethiopica infection. Two cases of the diffuse form of cutaneous leishmaniasis were observed. In this highland biotope, Phlebotomus pedifer was found to be the major, and possibly the only, vector for L. aethiopica. PMID- 1440774 TI - Comparison of parasitological and immunological methods in the diagnosis of leishmaniasis in Ethiopia. AB - The sensitivity and specificity of parasite demonstration methods (smear, culture and histology) and serological assays (enzyme-linked immunosorbent assay [ELISA], direct agglutination test and immunoblot) were compared in the diagnosis of leishmaniasis in Ethiopia. Culture was found to be the most sensitive diagnostic method, followed by ELISA, for the diagnosis of cutaneous leishmaniasis (CL). When the clinical type of CL was taken into consideration, serological and parasitological methods were equally good for the diagnosis of diffuse cutaneous leishmaniasis. Overall, the serological assays were not sensitive enough to diagnose all the parasitologically confirmed cases of localized cutaneous leishmaniasis. Both groups of diagnostic methods performed equally well in the diagnosis of visceral leishmaniasis patients. In cases of CL where clinical diagnosis was a problem and histology could not give a definitive diagnosis due to the absence of demonstrable parasites, one of the serological assays, preferably ELISA, was very useful in establishing the final diagnosis. PMID- 1440775 TI - Identification of Leishmania from mucosal leishmaniasis by recombinant DNA probes. AB - Three cases of mucosal leishmaniasis are described. Parasites isolated from mucosal lesions were identified by Southern blot analysis of their genomic deoxyribonucleic acids (DNAs) using recombinant DNA probe pDK20. Parasites from 2 patients were identified as Leishmania donovani s.l. One of the patients had pure mucosal lesions, while in the second patient there was dissemination of the parasite to other organs. The spectrum of the disease caused by L. donovani is discussed. The parasite from the third patient was identified as L. major. PMID- 1440776 TI - HIV-Leishmania co-infections in Italy. Isoenzyme characterization of Leishmania causing visceral leishmaniasis in HIV patients. AB - Visceral leishmaniasis (VL) infections in patients with human immunodeficiency virus (HIV) infection are dramatically increasing in Mediterranean countries such as Spain, France and Italy. A study has been carried out to characterize biochemically the agents of typical or unusual VL in subjects with HIV infection and to compare results with those obtained so far from VL and cutaneous leishmaniasis (CL) infections in HIV negative subjects. Twelve Leishmania stocks were isolated from 8 HIV patients and typed through the electrophoretic analysis of 14 isoenzymes. All the stocks were identified as L. infantum s.l. According to zymodeme classification, the results can be summarized as follows: (i) only half of the subjects were infected with the expected commonest viscerotropic zymodeme in the Mediterranean area, MON 1; (ii) 2 patients were infected with the most widespread agent of CL in Italy, L. infantum MON 24; (iii) one subject was found infected with a zymodeme (MON 78) which, so far, has been found only in Malta as an agent of CL; (iv) one subject was infected with a new zymodeme, MON 136, which shares biochemical characteristics with 2 dermotropic L. infantum zymodemes, MON 78 and MON 111. Thus, half of the HIV patients surveyed displayed severe visceralization of parasites usually showing low virulence in HIV negative subjects. PMID- 1440777 TI - A capture ELISA detects Giardia lamblia antigens in formalin-treated faecal samples. PMID- 1440778 TI - Enzyme-linked immunosorbent assay based on monoclonal and polyclonal antibodies for the detection of Entamoeba histolytica antigens in faecal specimens. AB - A murine monoclonal antibody (MAb) (Eh208C2-2) raised against crude lysate of the pathogenic HM-1:IMSS strain of Entamoeba histolytica was used in an enzyme-linked immunosorbent assay for the detection of E. histolytica antigens in faecal specimens. The detection limit of the assay was 110 and 280 amoebae/ml of the HM 1:IMSS and HK-9 strains in phosphate-buffered saline, respectively. The assay was applied to single stool samples from 3 groups of individuals comprising 40 patients whose stools were positive for E. histolytica trophozoites and/or cysts (group I), 48 patients whose stools were negative for E. histolytica but positive for other parasites (group II), and 36 parasitologically-negative healthy controls (group III). Positivity rates of 77.5%, 2.1% and 2.7% were found in samples from groups I, II and III respectively. Specificity, positive and negative predictive values, and efficiency of the assay were 97.6%, 93.9%, 90.1% and 91.1% respectively. When group I samples were further divided into a trophozoite-positive subgroup IA (13 samples) and a cyst-positive subgroup IB (27 samples), the positive rates were 100% and 66.7%, respectively (P < 0.025). PMID- 1440779 TI - Entamoeba histolytica: erythrophagocytosis, collagenolysis, and liver abscess production as virulence markers. AB - High rates of erythrophagocytosis and collagenolysis in vitro have been regarded as indicative of virulence in vivo of Entamoeba histolytica trophozoites. In the present study, the erythrophagocytic index and the collagenolytic activity of 3 axenic lines of E. histolytica, strain HM1:IMSS, were measured. The 3 lines shared the same pathogenic zymodeme but showed clear-cut differences in the extent of liver damage induced in hamsters. A direct correlation between collagenolysis in vitro and the size of liver abscesses produced by each line of E. histolytica trophozoites was found. In contrast, the line with the highest erythrophagocytic index produced small amoebic abscesses in hamsters, whereas the line with a relatively low erythrophagocytic index produced the largest liver lesions. It is concluded that the extent of collagenolytic activity is a better marker of virulence of E. histolytica cultured under axenic conditions than is erythrophagocytosis. PMID- 1440780 TI - Axenic cultivation of Entamoeba histolytica in suspension. PMID- 1440781 TI - Quantitative detection of schistosomal circulating anodic antigen by a magnetic bead antigen capture enzyme-linked immunosorbent assay (MBAC-EIA) before and after mass chemotherapy. AB - The magnetic bead antigen capture enzyme-linked immunosorbent assay (MBAC-EIA) has been applied to detect schistosomal circulating anodic antigen (CAA) in pre- and post-treatment sera from 55 individuals in a Schistosoma mansoni control project in the Blue Nile valley of western Ethiopia. The amounts of CAA detected by this assay were positively correlated with the numbers of eggs per gram of faeces (epg). A significant reduction in CAA levels as measured by the MBAC-EIA was observed after mass chemotherapy. The sensitivity was 88-89% in clinically significant cases excreting more than 100 epg. In light infections, however, the sensitivity was lower. None of 32 uninfected Norwegian blood donors or 12 Ethiopian immigrants to Norway were positive. The specificity was thus estimated to be 100%. The test is rapid (1-2 h) and simple to perform without sophisticated equipment and could therefore, with slight modification, be used as a reliable method of diagnosis at field level in endemic areas undergoing mass chemotherapy campaigns or population surveys. PMID- 1440782 TI - Serum laminin in hepatic schistosomiasis. AB - Serum laminin levels were measured in patients with chronic hepatic schistosomiasis. A significant increase in the mean serum laminin level was observed in 14 patients with hepatosplenic schistosomiasis (2.57 +/- 0.83 units/ml [standard deviation]) compared to the level in 10 patients with the hepatointestinal form of the disease (1.38 +/- 0.45 units/ml) and in the control group of 10 (1.15 +/- 0.31 units/ml). In the hepatosplenic patients there was a significant direct relation between serum laminin and percutaneous splenic pulp pressure (r = 0.68). However, this relation was not observed with either liver function tests or levels of N-terminal propeptides of type III procollagen. These findings are compatible with an increased production of laminin in hepatosplenic schistosomiasis, which may be related to the observed enlarged liver and spleen basement membranes in such disease. PMID- 1440783 TI - Preliminary study of the prevalence of human schistosomiasis in Richard-Toll (the Senegal river basin). PMID- 1440785 TI - Prevalence of hookworm infection and its association with low haematocrit among resettlers in Gambela, Ethiopia. AB - A cross-sectional survey of hookworm infection and haematocrit (HCT) levels was conducted in 7 resettled villages and 3 indigenous villages on sample populations selected by two-stage random sampling. Of 614 resettled persons and 187 indigenous persons, 65.5% and 60.4% respectively were infected with hookworm. Mean haematocrits for 664 resettled and 222 indigenous persons were 33.1% and 35.2%, respectively. A significant association (odds ratio = 2.65) was found between low haematocrit level (below the median for the sample population) and hookworm infection in the resettled population. Suggestions are made on the need for further studies and intervention programmes. PMID- 1440784 TI - Intestinal schistosomiasis: report of the first cases in Guinea Bissau. PMID- 1440786 TI - Natural infections of Dirofilaria immitis in Aedes (Stegomyia) polynesiensis and Aedes (Finlaya) samoanus and their implication in human health in Samoa. AB - Dirofilaria immitis infections were observed in Aedes polynesiensis and Ae. samoanus in Samoa, together with Wuchereria bancrofti infections, in a study on sub-periodic bancroftian filariasis during 1978-1980. In the 4 indicator villages, the infection rate in Ae. polynesiensis was 0.46% and the infective rate 0.09% (15,223 mosquitoes were dissected). The infection rate in Ae. samoanus was 0.20% and the infective rate 0.08% (10,089 dissected). In 45 selected villages throughout the country, Ae. polynesiensis infection and infective rates were 0.92% and 0.29% (7575 dissected) and the rates for Ae. samoanus were 0.21% and 0.07% (9093 dissected). Infection with D. immitis was comparable in degree and distribution to that with W. bancrofti. There was a steady and consistent exchange of parasites between the human and canine populations, creating conditions favourable for human dirofilariasis in Samoa. Clinicians are warned against this probable human infection. PMID- 1440787 TI - Serological evaluation of the 12 kDa subunit of antigen B in Echinococcus granulosus cyst fluid by immunoblot analysis. AB - This study evaluated the 12 kDa (smallest) subunit of Echinococcus granulosus antigen B as a diagnostic molecule. Using immunoblotting, 90.9% of cystic hydatid patients, 40% of alveolar hydatid patients and 5.5% of cysticercosis patients showed sero-reactivity to this subunit. Human antibody response to the 12 kDa molecule appeared independent of factors such as parasite strain or host population responsiveness. The majority of infection sera, and some normal human controls, also recognized the 38 kDa subunit of antigen 5. PMID- 1440788 TI - Dengue 1 epidemic in French Polynesia, 1988-1989: surveillance and clinical, epidemiological, virological and serological findings in 1752 documented clinical cases. AB - An epidemic of dengue 1 occurred in French Polynesia in December 1988 and June 1989. This paper records (i) the trend of the outbreak and its surveillance and (ii) the clinical, epidemiological and virological data obtained from 1752 documented cases. The epidemic reached its peak in February in Tahiti Island, 7 weeks after its recognition. Among 6034 suspect cases reported by sentinel physicians, 60.3% were < 20 years old. The illness was classical dengue. No fatality or case of dengue haemorrhagic fever/dengue with shock syndrome was reported. Of 4792 patients subjected to laboratory testing, 41% were confirmed as positive. The serological attack rate was c. 40%. The estimated number of dengue infections in the Windward Islands was about 20,000. Transmission was associated with Aedes aegypti. Study of documented cases showed a higher confirmation rate in both the civilian population < 15 years old (46.5%) and the susceptible French military population (47.6%) than in older civilians (31.1%, P < 0.05). Furthermore, primary dengue infections were predominant in both of the first 2 groups. The diagnosis was mostly confirmed (i) by virus isolation on day < 5 of illness and (ii) by detection of immunoglobulin (Ig) M on day > or = 5 of illness. The study showed that adequate surveillance of an epidemic requires both clinically and laboratory-based systems. PMID- 1440789 TI - Rift Valley fever antibody in human sera collected after an outbreak in domestic animals in Kenya. PMID- 1440790 TI - An outbreak of typhoid due to multidrug resistant Salmonella typhi in Pondicherry. AB - An outbreak of typhoid due to multi-drug resistant Salmonella typhi is reported from Pondicherry, India. While the average prevalence of drug resistant strains in 1980-1988 had been 11.7%, it increased to 52% in 1989-1990. The majority of strains (80.8%) were resistant to chloramphenicol, streptomycin, tetracycline and ampicillin; 40% were resistant to co-trimoxazole. Minimum inhibitory concentrations to 8 antibiotics for 17 representative strains were more than 10 fold greater than those of 13 sensitive strains. The multi-resistance was shown to be plasmid mediated in direct conjugation experiments and the strains belonged to Viphage type O, biotype II. PMID- 1440791 TI - Risk factors in transmission of brucellosis from animals to humans in Saudi Arabia. AB - A case-control study was undertaken to determine for the first time the specific aetiology of animal to human transmission of brucellosis in Saudi Arabia. Cases consisted of all patients with brucellosis attending the primary care clinic of the Riyadh Al-Kharj Hospital programme in central Saudi Arabia. A sample of individually matched controls was selected concurrently from patients attending the same clinic for unrelated problems. Cases and controls responded to a 48 item questionnaire on exposure to established risk factors for brucellosis. Greatest risk was found to be associated with indirect contact with animals (the consumption of unpasteurized dairy products), as opposed to direct contact with animals. When specific animal products were considered, greatest risk was associated with the consumption of milk and laban (buttermilk), as opposed to cheese or uncooked liver. When specific animal species were considered, greatest risk was associated with products derived from sheep and goats as opposed to camels and cattle. When direct contact with animals was considered, the study found a very high risk associated with assisting in animal parturition, but no significant risk associated with other direct (unspecified) animal contact. PMID- 1440792 TI - Oligonucleotide probes to identify three sibling species of the Anopheles farauti Laveran complex (Diptera: Culicidae). AB - We have sequenced recombinant plasmid probes for each of 3 Anopheles farauti complex species and identified internal oligonucleotides of 25-26 base pairs, specific for each member of the complex. Synthetic oligonucleotides oAf1, oAf2 and oAf3, when radiolabelled and hybridized with deoxyribonucleic acid from An. farauti, reacted as highly specific probes for An. farauti numbers 1, 2 and 3 respectively. These probes are effective on air-dried or alcohol-preserved larval, pupal or adult specimens. PMID- 1440793 TI - A simplified, non-radioactive DNA probe protocol for the field identification of insect vector specimens. PMID- 1440794 TI - Persistent and acute diarrhoea as the leading causes of child mortality in urban Guinea Bissau. AB - An investigation of child mortality in a semi-urban community, Bandim II, in the capital of Guinea Bissau was carried out from April 1987 to March 1990. 153 deaths were recorded among 1426 live-born children who were followed for 2753 child-years. The under-five mortality risk was 215 per 1000 children (95% confidence interval [CI] 176-264), infant mortality 94 per 1000 (95% CI 73-115), and perinatal mortality 52 per 1000 (95% CI 41-63). By prospective registration of morbidity, post-mortem interviews, and examination of available hospital records, a presumptive cause of death was established in 86% of the deaths. Persistent and acute diarrhoea were the most frequent causes of death, accounting for 43 and 31 deaths per 1000 children, respectively. Fever deaths (possibly malaria), neonatal deaths, acute respiratory infections, and measles were other frequent causes. The access to health services was relatively easy: 75% of the children who died had attended for treatment at a hospital or a health centre. It is important to find ways of preventing and managing persistent diarrhoea, the major cause of death, and to improve the control of acute diarrhoea by a targeted approach. PMID- 1440795 TI - Atropine poisoning after eating chapattis contaminated with Datura stramonium (thorn apple). PMID- 1440796 TI - Intestinal pathogens and parasites in Australian aboriginal children from birth to two years of age. PMID- 1440797 TI - Multiresistant Salmonella typhi infection in Cairo. PMID- 1440798 TI - Proper requirements for the QBC malaria test. PMID- 1440799 TI - Intestinal parasitic infections: a soluble public health problem. PMID- 1440800 TI - Prognostic significance of rises in parasitaemia during treatment of falciparum malaria. AB - Transient rises in parasitaemia occur commonly during the treatment of falciparum malaria but their prognostic significance has not been well defined. Twelve hourly parasite counts from 133 malaria patients who were ultimately cured were therefore compared with counts from 97 therapeutic failures to determine if increase in parasitaemia was a useful early indicator of poor treatment response. Parasitaemia in both groups frequently rose during the initial 12 h of therapy (41% of all patients), but rising counts thereafter were rarer in treatment successes (P < 0.01). The relative risk of treatment failure was 3.8 if the count was higher at 24 h than 12 h, rose to 7.8 for increases at 48-60 h, and was 13.7 and 19.4 for counts above admission levels at 48 h and 60 h. These data suggest a way to identify patients at high risk of treatment failure. PMID- 1440801 TI - Acute renal failure, acute rhabdomyolysis and falciparum malaria. PMID- 1440802 TI - Insecticide impregnation can restore the efficiency of torn bed nets and reduce man-vector contact in malaria endemic areas. AB - Three trials with torn bed nets impregnated with permethrin and deltamethrin were made under field conditions at the Soumousso Field Station and the Vallee du Kou rice-field area, both in Burkina Faso, and the Djoumouna fish pond area in the Congo Republic. Even a considerably torn correctly impregnated bed net could be an useful method for limiting human-anopheline contacts. But bed nets in poor condition, i.e. too little impregnated and too much torn, cannot protect the users against anopheline bites. Protection increases with insecticide concentration, but at a high dosage insecticide could have more a repellent than a killing effect. Therefore a balance has to be found for the optimum rate of insecticide treatment of bed nets to obtain a real reduction in malaria transmission and morbidity, in every epidemiological situation. PMID- 1440803 TI - The effect of artemisinine, its derivatives and mefloquine against chloroquine resistant strains of Plasmodium falciparum in vitro. AB - A 48 h in vitro test of the efficacy of artemisinine, dihydroartemisinine, artemether, mefloquine and chloroquine was carried out against 3 chloroquine resistant strains of Plasmodium falciparum, strains K1 and T996 from Thailand and LS21 from India. A sigmoid Emax model was fitted to all in vitro inhibition data for each combination of drug and strain. Strains K1 and LS21 were strongly resistant to chloroquine, whereas T996 was partially resistant. Artemisinine, dihydroartemisinine and artemether were active against all strains, with complete growth inhibition at 10(-7) M. Artemether and dihydroartemisinine were both more potent than artemisinine, with 50% effective (EC50) values of 0.57-1.6 nM and 0.36-3.1 nM respectively; the EC50 of artemisinine was 1.5-6.1 nM for the 3 strains. The EC50 values for mefloquine were 46-185 nM. At higher concentrations, strains K1 and LS21 were fully inhibited, while with strain T996 mefloquine did not fully inhibit even at the highest concentration, 1.28 x 10(-6) M. It is concluded that artemisinine and its derivatives were highly effective against the 3 chloroquine-resistant strains, one of which showed borderline resistance to mefloquine. PMID- 1440804 TI - The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro. AB - The clinical efficacy of two doses of mefloquine (15 and 25 mg/kg body weight) was evaluated in 85 children suffering from acute symptomatic falciparum malaria. The cure rate on day 28 was 100% in both groups. There was no significant difference (P > 0.05) in the mean parasite and fever clearance times in both groups (48.5 +/- 14.6 and 32.0 +/- 12.7 h respectively for the 25 mg/kg group and 49.0 +/- 15.1 and 30.0 +/- 13.3 h respectively for the 15 mg/kg group). There was also no significant difference (P > 0.05) in these values between children with hyperparasitaemia (53.6 +/- 11.1 and 36.0 +/- 17.0 h respectively) and those without hyperparasitaemia (49.1 +/- 13.6 and 31.8 +/- 14.6 h respectively). Recurrence of parasitaemia was observed after day 30 in 2 patients in the 15 mg/kg group and in 1 patient in the 25 mg/kg group. In vitro, 3 of 21 isolates showed reduced susceptibility to mefloquine, with minimum inhibitory concentrations (MIC) > 67 nM/litre. The MIC and 50%, 90% and 99% inhibitory concentrations were 200.8, 6.27, 31.7 and 119.6 nM/litre respectively. Four of 22 isolates were resistant to chloroquine (MIC > 108 nM/litre). Isolates that showed low sensitivity to mefloquine in vitro were sensitive to chloroquine in vitro, and the 4 that were resistant to chloroquine were sensitive to mefloquine. Irrespective of MIC and dose of mefloquine, parasitaemia cleared in all subjects in 96 h or less.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440805 TI - Drug sensitivity studies during a highland malaria epidemic in Kenya. PMID- 1440806 TI - Ciprofloxacin does not achieve radical cure of Plasmodium falciparum infection in Sierra Leone. AB - Recently, activity in vivo of norfloxacin has been reported against Plasmodium falciparum and, in vitro, ciprofloxacin has been found to be even more potent than norfloxacin. We therefore treated one patient infected with chloroquine resistant P. falciparum at relatively low parasite density with ciprofloxacin, 200 mg intravenously twice daily for 3 d. This treatment failed to produce radical cure, although some suppressive effect was probably obtained. The growth of the P. falciparum isolate in vitro was inhibited at 12.5 micrograms/ml, whereas the plasma concentration recorded 1 h after infusion was only 1.2 microgram/ml. It is concluded that, if ciprofloxacin is to be used for treatment of malaria, a higher dose than that normally used for bacterial infections is necessary. PMID- 1440807 TI - Chronotherapy of malaria: improved efficacy of timed chloroquine treatment of patients with Plasmodium falciparum infections. AB - The effect of routine treatment with chloroquine (10 mg/kg on days 1 and 2 and 5 mg/kg on day 3) on parasitaemia and parasitaemic profile of patients infected with Plasmodium falciparum was studied. As with P. vinckei petteri, the mid-term trophozoites of P. falciparum were the most susceptible stages to chloroquine treatment. It is suggested that, in order to diminish the frequency of drug administration and to lower the risks of chemoresistance developing, treatment should be diversified, using the drug which is most effective on the parasite stages present in the peripheral blood. PMID- 1440808 TI - Increase of chloroquine resistance in vivo of Plasmodium falciparum over two years in Edea, south Cameroon. PMID- 1440809 TI - Alpha-1-acid glycoprotein inhibits the effect of quinine on the growth of Plasmodium falciparum in vitro. PMID- 1440810 TI - Use of the fluorochrome benzothiocarboxypurine in malaria diagnosis. PMID- 1440811 TI - Epidemic visceral leishmaniasis in southern Sudan: identity and systematic position of the parasites from patients and vectors. AB - Twenty-five strains of Leishmania donovani isolated from humans and Phlebotomus orientalis in an epidemic area of southern Sudan were shown to belong to 3 very similar zymodemes: MON 18 (11 strains), MON 30 (1 strain) and MON 82 (13 strains). The 3 zymodemes are very closely related and seem to behave as a single population. PMID- 1440812 TI - Isoenzyme characterization of Leishmania braziliensis braziliensis isolates obtained from Bolivian and Peruvian patients. AB - Thirty-four Leishmania isolates obtained from Bolivian and Peruvian patients infected with mucocutaneous leishmaniasis were characterized by isoenzyme electrophoresis using 10 enzymatic markers; all belonged to the subspecies L.b. braziliensis. Three isolates showed marked variation compared with the reference strain with respect to 5 or 6 enzymes. These variant isolates originated from patients with forms of the disease which were unresponsive to treatment. PMID- 1440813 TI - Haemoculture of Leishmania (Viannia) braziliensis from two cases of mucosal leishmaniasis: re-examination of haematogenous dissemination. AB - Leishmania parasites were isolated from peripheral blood leucocytes of 2 patients with mucosal disease among a total of 23 parasitologically confirmed cases of leishmaniasis. One had had mucosal leishmaniasis for 4 years and active pulmonary tuberculosis was also diagnosed. The other patient presented a cutaneous lesion on his right leg of 3 months duration and asymptomatic mucosal involvement. He had received intravenous antimonials before isolation of parasites. Both patients had positive indirect fluorescent antibody and Montenegro skin tests. L. (Viannia) braziliensis was isolated from both patients. This culture of parasites from leucocytes provided direct evidence for metastatic spread of Leishmania via the blood. PMID- 1440814 TI - A kit for in vitro isolation of trypanosomes in the field: first trial with sleeping sickness patients in the Congo Republic. PMID- 1440815 TI - High cell surface hydrophobicity of virulent Entamoeba histolytica isolates. AB - Thirty isolates of Entamoeba histolytica were examined for their cell surface hydrophobicity. It was observed that increased hydrophobicity of the trophozoites was associated with lesion-forming ability in hamster liver, a higher rate of erythrophagocytosis and greater resistance to complement. The relationship of cell surface hydrophobicity to other virulence markers in E. histolytica is discussed. PMID- 1440816 TI - Pneumocystis carinii as a cause of pneumonia in HIV-infected patients in Lusaka, Zambia. PMID- 1440818 TI - Schistosoma haematobium infection in Egyptian schoolchildren: demonstration of both hepatic and urinary tract morbidity by ultrasonography. AB - Parasitological, clinical and ultrasonographical studies were performed upon 422 schoolchildren aged 12-16 years living in a village in the Fayoum where Schistosoma haematobium, but not S. mansoni, was transmitted. Over half of the children gave a history of receiving praziquantel therapy during the preceding 2 years. Symptoms (e.g., haematuria, burning micturition), signs (e.g., hepatomegaly, splenomegaly) and urinary findings (e.g., haematuria, proteinuria) correlated better with the presence and intensity of S. haematobium infection after correcting for this variable. Renal obstructive lesions detected by ultrasound were 2 and 3 times as common in those with moderate and heavy infections as in those with no or light infections, and urinary bladder wall lesions were far more frequent in those with moderate and heavy infections. A mild grade of periportal fibrosis, hepatomegaly and splenomegaly were present in some children in all groups. However, the prevalence of splenomegaly correlated directly with the intensity of infection; liver lesions occurred much more frequently in children with infection or a history of treated infection than in non-infected children denying recent treatment; and no child had hepatomegaly or splenomegaly in the absence of periportal fibrosis. PMID- 1440817 TI - An epidemiological study of a Schistosoma intercalatum focus in south-east Gabon. AB - A Schistosoma intercalatum focus in south-east Gabon was studied between July 1989 and July 1990. Among the 356 permanent residents in the village, 354 provided stool specimens and 101 (28.5%) were excreting eggs (geometric mean of egg density = 101.4 eggs/g, with a range of 1-3200). The pattern of prevalence and intensity of infection with age showed the curve usually found in schistosomiasis, i.e. increasing during the first 2 decades of life and then gradually decreasing. The analysis by stepwise logistic regression of factors shown to be important in determining infection in other schistosomiasis clearly demonstrated the significant and independent effects of both age and water contact on infection by S. intercalatum. These similarities with other schistosomal infections could indicate that similar immune mechanisms were operating. Urine from 284 subjects, of whom 90 were egg excreters, was tested for circulating antigen by enzyme-linked immunosorbent assay using a Schistosoma genus-specific monoclonal antibody (Sm 10.27.12). The test was positive for 90 subjects but only 35 of these were egg excreters. Although S. intercalatum is usually considered of low pathogenicity in man, this study showed a relationship between egg excretion and both splenomegaly and lower haemoglobin levels, even after taking into account the confounding presence of Plasmodium falciparum. PMID- 1440819 TI - Schistosome circulating anodic antigen in serum of individuals infected with Schistosoma japonicum from the Philippines before and after chemotherapy with praziquantel. AB - The presence of the schistosome circulating anodic antigen (CAA) in serum of patients infected with Schistosoma japonicum from The Philippines has been investigated using an enzyme-linked immunosorbent assay (ELISA). Serum samples were tested from 48 patients who excreted S. japonicum eggs, 9 individuals with a negative stool examination, and 20 controls with both a negative stool and a negative circumoval precipitin test. No false positive result was detected for the unequivocally negative controls. CAA could be demonstrated in 72.9% of the egg-excreting patients. A positive correlation between parasite burden (eggs per gram of faeces) and antigen level (CAA titre) was found (Spearman's rho = 0.48, P < 0.001, n = 48). Four of 18 sera from the egg-negative individuals were positive in the ELISA. In view of the fact that anti-worm antibodies were also detected in these 4 sera, those reactions suggest active infection not detected by stool examination. In serum from patients treated with praziquantel, a significant drop in CAA titre was seen within 5 d after treatment (Wilcoxon's chi T = -2.23, P = 0.0258, n = 21). In conclusion, the detection of CAA by ELISA in S. japonicum infection can give valuable information in both individual diagnosis and therapeutic drug monitoring, as well as in epidemiological studies or disease control programmes. PMID- 1440820 TI - Wuchereria bancrofti infection in human and mosquito populations of a Polynesian village ten years after interruption of mass chemoprophylaxis with diethylcarbamazine. AB - In 1991, a study on Wuchereria bancrofti microfilariae (mf) and infection rates was carried out in the human and mosquito populations of a Polynesian village where, 10 years before, the mf prevalence rate was 6.4% and twice-yearly mass treatment with 3 mg/kg of diethylcarbamazine (DEC) was interrupted. Venous blood samples were collected from 575 (97%) individuals aged 15 years or more, of whom 122 (21.4%) were mf positive. The mf carrier prevalence rate was 27.4% in males, significantly higher than that of 14% in females; it increased from 7-12% in the youngest age group (15-19 years) to 40-50% in the oldest (> or = 60 years) for both males and females. 387 mosquito collections were performed and 1748 female Aedes polynesiensis were dissected, of which 1176 were parous. Among the latter, 114 (9.7%) were infected with Wuchereria bancrofti larvae at L1, L2 or L3 stages. The mean number of larvae per mosquito was 2.46 (range 1-15). Of the 114 infected mosquitoes, 30 harboured L3 larvae, giving a 2.55% infective rate; the mean number of L3 larvae per mosquito was 1.15 (range 1-2). Such findings indicate that the interruption of systematic twice-yearly mass treatment with DEC (3 mg/kg) has resulted, after 10 years, in a substantial increase of microfilarial prevalence in humans, and in high infection rates in mosquitoes. PMID- 1440821 TI - Therapeutic effect of triclabendazole in patients with paragonimiasis in Cameroon: a pilot study. PMID- 1440822 TI - Albendazole for the treatment of human gnathostomiasis. AB - The efficacy of albendazole was investigated in 112 patients with symptomatic gnathostomiasis; 49 received 400 mg twice daily, 51 received 400 mg once daily, and 12 patients received placebo, all for 21 d. Subsequent follow-up was for 6 months. Cure (no further swelling) was seen in 93.9% and 94.1% of the treatment groups but in none of the placebo group. Additionally, reductions in eosinophil counts and in immunoglobulin G antibody were observed after treatment. Side effects were minimal. Albendazole may be an effective compound for the treatment of gnathostomiasis. PMID- 1440823 TI - Infectivity of irradiated and non-irradiated metacestodes of Taenia saginata. PMID- 1440824 TI - Immunoblot (western blot) and double diffusion (DD5) tests for hydatid disease cross-react with sera from patients with cysticercosis. PMID- 1440825 TI - Hepatitis delta virus infection in Bombay. AB - From June 1985 to June 1989, sera from 425 cases of acute viral hepatitis were gathered from 2 hospitals in Bombay; 331 sera were positive for hepatitis B surface antigen and immunoglobulin M anti-hepatitis B core antigen, and the donors' disease was diagnosed as hepatitis B. Anti-hepatitis D virus was found in 124 of these sera, and hepatitis D antigen was present in 24 more, conclusively proving the presence of hepatitis delta infection in association with hepatitis B in Bombay. Among the 425 cases of hepatitis, 39 cases of fulminant hepatitis developed, of whom 31 died. Hepatitis B virus (HBV) was the apparent viral infection in 32 of the fulminant cases, and 20 (63%) of them also showed evidence of hepatitis D virus (HDV) infection, suggesting an aggravation of their clinical course due to concurrent HBV and HDV infections. PMID- 1440826 TI - Aflatoxin exposure, malaria and hepatitis B infection in rural Gambian children. AB - Aflatoxin-albumin adduct levels were measured in serum samples obtained from a group of Gambian children. The relationships between exposure to aflatoxin and the prevalence of malaria, between exposure and humoral and cellular responses in vitro to defined malaria antigens and, amongst children with evidence of exposure to hepatitis B infection, between aflatoxin and carriage of the hepatitis B surface antigen (HBsAg), were assessed. Aflatoxin-albumin adduct was found in nearly all serum samples collected during a survey performed at the end of the dry season and levels of adduct were generally high (up to 720 pg aflatoxin lysine equivalent/mg albumin). Higher levels of aflatoxin-albumin adduct were detected in Wollof children than in children of other ethnic groups and marked variation in mean adduct levels between villages was observed. Aflatoxin-albumin adduct levels were higher in children who were HbsAg positive and in children with Plasmodium falciparum parasitaemia than in controls. However, levels of adduct had no consistent effect on either malaria-specific antibody responses, lymphoproliferative responses in vitro, or morbidity from malaria during the subsequent rainy season. Much lower levels of aflatoxin-albumin adduct were detected in repeat samples obtained at the end of the rainy season. There was poor correlation between dry and rainy season levels of adduct in individual children. We have shown that Gambian children are exposed to high levels of aflatoxin. The seasonal variation of aflatoxin-albumin adduct and marked fluctuation of adduct with time in individual children need to be considered in the future planning of epidemiological studies using this marker of exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440827 TI - The role of sexual transmission in the epidemiology of hepatitis C virus in black South Africans. AB - The role of sexual transmission of hepatitis C virus in Black South Africans was evaluated by a seroprevalence study of sentinel populations at varying risk for sexually transmitted diseases (STD). Prevalence of anti-hepatitis C virus antibodies was found to be 1.8% in an STD clinic sample of 272, 0.7% in a family planning sample of 148, 3.3% in a sample of 246 'blue collar' workers (81% of rural origin), and 0.9 in a sample of 117 new blood donors. All samples were from Black adults. The differences between them were not significant (P = 0.2348). In contrast, the prevalence of anti-human immunodeficiency virus antibodies in the STD sample (5.5%) was statistically significantly different (P = 0.00095) from the family planning clinic sample (1.4%) and the blue collar sample (0.8%) as well as from the reported prevalence for black blood donors in the Johannesburg area (0.7%). No evidence supporting a role for sexual transmission of hepatitis C virus was found, while the prevalence of infection appeared to be higher in rural populations and in males. These features are similar to hepatitis B in this population. PMID- 1440828 TI - HTLV-1 has reached Thailand via a heterosexual route. PMID- 1440829 TI - A short term projection of HIV infection and AIDS cases in Cameroon. AB - By September 1991 Cameroon had reported 650 cases of the acquired immune deficiency syndrome (AIDS). The results from the sentinnel surveillance system showed a seroprevalence of human immunodeficiency virus (HIV)1 of 1.3% among pregnant women, 2.5% in people attending sexually transmitted disease clinics and 3.5% in tuberculosis patients in 1990. The estimated number of persons infected with HIV varies between 10,000 and 30,000. The World Health Organization projection model was used to make a short-term projection of HIV infection and AIDS cases; it indicated that the number of persons infected with HIV will double by the year 1995, with an estimated 8500 AIDS cases. Even in a low prevalence country such as Cameroon, the impact of the HIV epidemic is important and will result in a burden for the health care system. PMID- 1440830 TI - Rabies: is provocation of the biting dog relevant for risk assessment? PMID- 1440831 TI - Plague in Lushoto district, Tanzania, 1980-1988. AB - Rodents were live-trapped in selected plague-inflicted villages from June 1980 to March 1988. Flea infestation rates were determined and the animals were serologically tested for plague. Clinically suspected and clinically healthy people in the affected areas were similarly tested for plague antibodies. Of 1596 rodent sera tested, 91 (5.7%) were positive for plague. These were mostly from Rattus rattus, Mastomys natalensis, Otomys spp. and Pelomys fallax. A total of 1772 fleas, of which Dinopsyllus lypusus, Xenopsylla brasiliensis and Ctenophthalmus calceatus comprised the largest proportion, was collected from the captured rodents. Total flea indices ranged from 0.67 to 1.12 fleas per rodent. A total of 2809 human cases and a mortality rate of 10.2% were recorded in 1980 1988. It was concluded that most rodent species in the area were suitable reservoirs of plague and that D. lypusus, X. brasiliensis and C. calceatus were probably responsible for transmitting the pathogen. Lack of effective quarantine measures during outbreaks was partly responsible for the spread of the disease to many villages, while inadequate rodent and flea control and poor sanitary measures could be responsible for continued outbreaks of plague in the area. PMID- 1440832 TI - Short-course treatment of typhoid fever with ciprofloxacin in south India. AB - This study assessed the performance of short-course ciprofloxacin for the treatment of 34 adult patients with culture-positive typhoid fever. Patients received ciprofloxacin, 750 mg orally twice daily for 7 d. Measurement of response was based upon time from initial treatment to fever lysis, to afebrile state, and to symptom resolution. Ciprofloxacin-treated patients defervesced in a mean of 3.21 d (+/- 0.56), with stabilization of temperature in 4.0 +/- 0.73 d. After 90 d follow-up, no relapse or carrier was identified. Side effects during therapy were minimal. PMID- 1440833 TI - An evaluation of the hydrogen sulphide water screening test and coliform counts for water quality assessment in rural Malaysia. AB - The H2S water screening test and the membrane filtration faecal coliform count were compared with Escherichia coli counts for water samples collected from household water sources and domestic drinking water in rural Malaysia. Water samples were taken from 151 wells, 44 taps supplying water from the treated municipal supply and 192 domestic stored water supplies. E. coli were detected in 20% of the samples (42% of wells, 7% of tap water and 6% of drinking water). Excellent correlation (Spearman's rank correlation rs = 0.93) was found between the faecal coliform and E. coli counts for all sample types. The H2S method was poorly correlated whether read at 18 or 30 h. False positive rates were highest for well water, and false negative rates were highest for both well and drinking water samples, with low E. coli counts. The faecal coliform test was an excellent predictor of the presence of E. coli in these water samples, while the H2S test was very inadequate. PMID- 1440834 TI - Corneal ulceration in Tanzanian children: relationship between measles and vitamin A deficiency. AB - Two 3-year prospective studies from 1982-1984 and 1986-1988 in Tanzania identified 189 children with corneal ulceration, of whom 31 (16.4%) were due to vitamin A deficiency. In 1982-1984, vitamin A deficiency was responsible for 23.4% of corneal ulcers (25 of 107) compared with 7.3% (6 of 82) from 1986-1988 (P = 0.006). It is postulated that the decrease in corneal ulceration due to vitamin A deficiency can be attributed to improved measles immunization coverage. PMID- 1440835 TI - Corneal ulceration in Tanzanian children: relationship between malaria and herpes simplex keratitis. AB - Two 3-year prospective studies from 1982-1984 and 1986-1988 in Tanzania identified 189 children with corneal ulceration, of whom 92 (48.7%) were due to herpes simplex keratitis. In 1982-1984 herpes simplex keratitis was responsible for 35.5% of corneal ulcers (38 of 107), compared with 65.8% (54 of 82) in 1986 1988 (P = 0.00006). It is postulated that the increase in corneal ulceration due to herpes simplex keratitis can be attributed to an increase in the incidence and severity of malaria infection. PMID- 1440836 TI - Haematemesis and severe anaemia due to a pharyngeal leech (Myxobdella africana) in a Kenyan child: a case report. PMID- 1440837 TI - Treatment of envenoming by Mesobuthus tamulus (Indian red scorpion). PMID- 1440838 TI - Diagnosis of malaria in the field by fluorescence microscopy using QBC capillary tubes. PMID- 1440839 TI - Pentamidine in blood. PMID- 1440840 TI - American Association of Blood Banks, 45th annual meeting. San Francisco, California, November 7-12, 1992. Abstracts. PMID- 1440842 TI - Successful extended lung preservation with UW solution. AB - Maximum preservation times of 4-6 hr continue to plague lung transplantation. The high-potassium colloid University of Wisconsin solution (UWS) has proved superior to the crystalloid modified Eurocollins' solution (ECS) for preservation of the liver, kidney, and pancreas. The purpose of this study was to compare UWS and ECS for extended lung preservation using a technique of combined pulmonary and bronchial artery perfusion. Simultaneous pulmonary artery and bronchial artery (via a closed aortic segment) perfusion was employed to harvest the lungs of ten mongrel dogs (wt 25-35 kg) using either UWS (n = 5) or ECS (n = 5) preservation solutions. Following 17 hr of cold (4 degrees C) pulmoplegic storage, the lungs were placed in an isolated perfused working lung (IPWL) apparatus. Seven freshly harvested lungs served as a control group (CON). Lung aerodynamics and gas exchange were evaluated at standard intervals until failure of the lung on the IPWL apparatus. Time until failure (mean +/- SEM) for each group was: CON = 209 +/- 14 min; UWS = 227 +/- 26 min; and ECS = 123 +/- 29 min. Only one of the ECS lungs lasted longer than 90 min. UWS-preserved lungs displayed a gas exchange efficiency equal to the CON group and better than that in the ECS-preserved lungs (lower A-aDO2, lower intrapulmonary shunt), suggesting better protection of the alveolar capillary membrane. Although the UWS lungs were initially less compliant than the ECS lungs, at no time was there a significant difference in the total work of respiration between the two groups. We conclude that UWS provides superior protection of the alveolar capillary membrane. The aerodynamic disadvantages of UWS preservation did not effect lung survival or total work of respiration. PMID- 1440841 TI - Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets. AB - Long-term euglycemia by intraperitoneal transplantation of microencapsulated islets has not been described in the diabetic large animal model. In this study, we report the successful long-term reversal of diabetes by this method in spontaneous diabetic dogs. We have identified fundamental mechanism(s) associated with alginate-based microcapsule fibrosis, and have devised methods to ameliorate this problem. These include the use of purified alginate of low mannuronic acid content and cytokine suppression. Ten insulin-dependent, spontaneous diabetic dogs (insulin requirement 1-4 units/kg/day; absence of circulating C-peptide and diabetic K-values of 0.6 +/- 0.4) were entered into the study. Islets from mongrel donor pancreata were isolated and transplanted intraperitoneally either as free islet controls (n = 3) or as microencapsulated islet allografts (n = 7). In all seven encapsulated islet recipients, euglycemia was achieved within 24 hr (serum glucose failing from 304 +/- 117 to 116 +/- 72 mg/dl). IVGTT performed 14 days after islet transplant demonstrated normalization of K-values changing from a pretransplant level of 0.6 +/- 0.4 to 2.6 +/- 0.6. All animals receiving encapsulated islets remained euglycemic, free of the need for exogenous insulin, for a period of 63-172 days, with a median insulin-independence for 105 days. In contrast, recipients receiving free islets rejected their graft within seven days of implantation. In conclusion, this is the first report of long-term successful reversal of spontaneous diabetes in the large animal model by an intraperitoneal injection of encapsulated islets. The potential exists for this form of therapy to be explored in the treatment of type I diabetes in man. PMID- 1440843 TI - Bile secretion and histology of liver autotransplanted into the pancreatic parenchyma. AB - The pancreatic parenchyma was evaluated as a potential recipient site for hepatic fragment autotransplantation. Histologic and functional studies of hepatic autografts in the pancreas were performed in 15 mongrel dogs. Approximately 10 g of liver parenchyma was resected from each left lateral lobe. The remnant liver remained in situ. Bile secretion from the hepatic tissues implanted into the pancreas was estimated by measuring the indocyanine green (ICG)* concentration in pancreatic juice following intravenous ICG injection. One month following implantation, the hepatocytes in the pancreatic parenchyma were histologically colorless and did not have sinusoids. However, by the second month following implantation, hepatic nodules had grown extensively to become normal liver tissue, with sinusoids and a single liver cell-plate structure. At 4 months following intrapancreatic implantation the transplanted hepatic masses consisted of several hepatic lobules. Furthermore, ICG could be detected in the pancreatic juice of dogs surviving more than 2 months after implantation but no ICG could be detected in the pancreatic juice of normal controls. The present study provides direct evidence that hepatic grafts transplanted into the pancreas that has a ductal drainage system for bile secretion can reconstitute histologically normal liver tissue capable of secreting bile. This model can be used to understand the early steps of hepatic regeneration. PMID- 1440844 TI - The impact of arterialization on hepatic microcirculation and leukocyte accumulation after liver transplantation in the rat. AB - This study investigated the influence of hepatic arterialization on early graft function, microcirculation, and leukocyte-endothelial interaction after syngeneic orthotopic liver transplantation in Lewis rats. Livers were preserved for 17 hr in UW solution and transplanted without rearterialization (group 1: n = 10) or with immediate arterial reconstruction (group 2: n = 10). Graft function was analyzed by bile flow; microcirculation was assessed by laser Doppler flowmetry (LDF) and intravital microscopy (IVM). In addition, flow behavior of leukocytes was quantified by IVM after i.v. injection of the WBC marker acridine orange. Improved graft function in group 2 was indicated by increased bile production during the observation period of 90 min after reperfusion (7.18 +/- 0.62 vs. 3.63 +/- 0.63 ml/100 g liver [mean +/- SEM] P < 0.001). In arterialized grafts LDF values increased by 22.9 +/- 3.8% upon reperfusion of the hepatic artery (P = 0.004). Arterialization increased WBC velocities in sinusoids (group 1: 0.29 +/- 0.02 mm/sec, group 2: 0.34 +/- 0.01 mm/sec, P < 0.001) and postsinusoidal venules (0.43 +/- 0.05 vs. 0.64 +/- 0.05 mm/sec, P = 0.029). In addition, the number of nonperfused midzonal sinusoids decreased significantly (8.5 +/- 2.2% of all sinusoids analyzed vs. 4.2 +/- 1.3%, P = 0.048). However, the marked sinusoidal and venular WBC adherence observed 1 hr after reperfusion was not altered by arterialization. It is concluded that arterial reconstruction in rat liver transplantation improves microvascular perfusion and graft function but this improvement does not relate to WBC accumulation within the graft. We propose that studies on hepatic preservation and postischemic reperfusion in the rat should be based on the physiological model of dual vascularization. PMID- 1440845 TI - Ultrastructural changes and lipid peroxidation in rat adipomusculocutaneous flap isotransplants after normothermic storage and reperfusion. AB - Parallel in vivo, histological, and ultrastructural studies were carried out and markers of lipid peroxidation (Schiff's bases [SB] and thiobarbituric-acid reactive material [TBAR]) were measured in rat adipomusculocutaneous flap isotransplants that had been stored for 0, 2, 4, 6, and 8 hr under normothermic (37 degrees C) conditions and reperfused for specific periods. Flaps stored for 4 hr and treated with intravenous desferrioxamine (DFX) or hypertonic citrate flush (HCA) were also evaluated. In vivo assessment was made after 7 days of reperfusion. Flaps stored for 4 hr eventually exhibited partial necrosis in vivo, and neither DFX or HCA flush increased the area of surviving skin. Electron microscopy revealed extensive storage damage in epidermal, follicle, fat, and smooth muscle cells and in endothelium. HCA significantly preserved fat cells (P = 0.0035) and DFX diminished smooth muscle damage. Reperfusion injury was seen in endothelial cells in the form of swelling that was not prevented by HCA or DFX. Ultrastructural alterations correlated with changes in susceptibility to lipid peroxidation in fat but not in skin. The results of these parallel studies indicate that both free radical-dependent and independent mechanisms operate in ischemia and reperfusion injury in flap tissue and that fat has a greater predisposition to free radical damage than skin. PMID- 1440846 TI - Late airway changes caused by chronic rejection in rat lung allografts. AB - Airway disease after lung or heart-lung transplantation is one of late major complications, affecting the prognosis of the transplants. Little is known about the causes of airway changes. We performed rat lung transplantation and investigated the late airway changes of the long-term surviving lung grafts: allografts, BN to Lewis; isografts, BN to BN rat. All recipients were treated with CsA. We found airway changes, i.e., mucosal ulceration, granulation, submucosal fibrosis, which was located in the large airways, in four of five allografted lungs. The lung isografts showed no pathological abnormalities. Immunopathological studies disclosed the localized expression of MHC class II antigens on the bronchial epithelium of the large airways where recipient type dendritic cells accumulated in the submucosa and CD4 positive predominant lymphocytes infiltrated. These findings support the idea that the late airway changes in lung transplants are caused by immunologically mediated chronic rejection. PMID- 1440847 TI - Pharmacologic, toxicologic, and marrow transplantation studies in dogs given succinyl acetone. AB - A novel immunosuppressant, succinyl acetone (4,6-dioxoheptanoic acid), was studied in dogs. Results with bolus intravenous injections at doses ranging from 50 to 1600 mg/kg showed dose-dependent alpha and beta half-lives, ranging from 30 to 80 min and 7 to 27 hr, respectively. Results suggested that continuous i.v. infusion was necessary to maintain constant plasma levels. Four dogs were given 9.2 Gy total-body irradiation and autologous marrow transplants along with continuous i.v. infusion of succinyl acetone at 50, 100, 200, or 400 mg/kg/day for 21 days, and all four had rapid, sustained hematopoietic engraftment. However, two of the four dogs receiving 200 and 400 mg succinyl acetone/kg/day, respectively, developed bilateral hind-limb ataxia, with histologically confirmed cerebellar lesions in the dog given the higher dose, thus establishing a potential dose-limiting neurotoxicity. Prevention of graft-versus-host disease was studied in recipients of allogeneic marrow. Dogs were given 9.2 Gy TBI, followed by hematopoietic grafts from unrelated DLA-nonidentical or DLA haploidentical littermate dogs. Succinyl acetone was given as continuous infusion for 21 days after transplant at doses of 100-300 mg/kg/day. Starting succinyl acetone on the day of marrow infusion in four dogs failed to prevent rapid onset of acute GVHD, and dogs survived no longer than controls. Starting succinyl acetone 3 days before transplant delayed the onset of acute GVHD and prolonged survival significantly compared with that of dogs not given postgrafting immunosuppression (P = 0.008); survival was comparable to that in previously reported dogs given either methotrexate or cyclosporine as postgrafting immunosuppression (P = 0.88 and 0.99, respectively). Seven of the sixteen allogeneic recipients developed evidence of neurotoxicity during succinyl-acetone infusion. Neurological dysfunctions were manifested by hind-limb ataxia and posterior paresis. In conclusion, succinyl acetone significantly delayed the onset of GVHD and prolonged survival of DLA-nonidentical marrow graft recipients but did not induce graft-host tolerance and was associated with dose-limiting neurotoxicity. PMID- 1440849 TI - The use of radiolabeled anti-CD33 antibody to augment marrow irradiation prior to marrow transplantation for acute myelogenous leukemia. AB - Disease recurrence remains a major limitation to the use of marrow transplantation to treat leukemia. Previous transplant studies have demonstrated that higher doses of total-body irradiation result in less disease recurrence, but more toxicity. In this study, the possibility of delivering radiotherapy specifically to marrow using a radiolabeled anti-CD33 antibody (p67) was explored. Biodistribution studies were performed in nine patients using .05-.5 mg/kg p67 trace-labeled with 131I. In most patients initial specific uptake of 131I-p67 in the marrow was seen, but the half-life of the radiolabel in the marrow space was relatively brief, ranging from 9-41 hr, presumably due to modulation of the 131I-p67-CD33 complex with subsequent digestion and release of 131I from the marrow space. In four of nine patients these biodistribution studies demonstrated that with 131I-p67 marrow and spleen would receive more radiation than any normal nonhematopoietic organ, and therefore these four patients were treated with 110-330 mCi 131I conjugated to p67 followed by a standard transplant regimen of cyclophosphamide plus 12 Gy TBI. All four patients tolerated the procedure well and three of the four are alive in remission 195-477 days posttransplant. This study demonstrates the feasibility of using a radiolabeled antimyeloid antibody as part of a marrow transplant preparative regimen and also highlights a major limitation of using conventionally labeled anti-CD33--namely, the short residence time in marrow. Strategies to overcome this limitation include the use of alternative labeling techniques or the selection of cell surface stable antigens as targets. PMID- 1440848 TI - Hepatic artery pseudoaneurysm ligation after orthotopic liver transplantation--a report of 7 cases. AB - Pseudoaneurysm (PA) is a rare but life-threatening complication of liver transplantation. The authors present their experience on 7 patients treated by ligation of a post-OLT PA. Hepatic artery ligation or embolization was performed from 10 to 70 days after liver transplantation. Of the seven patients, four survived, one developed a biliary stricture, treated by percutaneous balloon dilatation, two died of a complication not related to treatment, and one died of multiple organ failure. PMID- 1440850 TI - Advantages of cyclosporine as sole immunosuppressive agent in children with transplanted kidneys. AB - A prospective study of intentional stopping of steroids 6 months after transplantation was done with 29 pediatric renal transplant recipients with a mean age of 10.4 +/- 3.4 years. Immunosuppression consisted of cyclosporine and methylprednisolone. We stopped giving MP to 24 children: to twenty after six months, four after 11-20 months. "Crude graft survival" was 97% during a mean follow-up of 36.7 +/- 15 months. The rejection rate was 48% during the first 6 months and 29% in the period after stopping MP. At present, 20/24 children (83%) have remained on CsA alone (18 patients) or CsA and azathioprine (2 patients) during a mean follow-up of 30 +/- 17 months. CsA nephrotoxicity occurred in 20.6% of patients, gum hypertrophy in 45%, hypertrichosis in 24%, and neurological symptoms in two patients (6.8%). Linear growth significantly improved after stopping MP: mean catch-up growth for prepuberal children 1.38 height standard deviation score (HSDS) and for pubertal children 1.6 HSDS. Bone age did not increase more rapidly than chronologic age. Weight/height index (W/HI) also improved. There was also a significant reduction in the use of antihypertensive drugs. Calculated glomerular filtration rate was decreased, though not significantly, after stopping MP. Thus, when graft survival is good, stopping corticosteroids corrects the major handicap of children with irreversible uremia- the poor linear growth--and improves the W/HI and control of arterial pressure. Longer follow-up periods are necessary to exclude significant worsening of renal function and an increased incidence of chronic rejection after stopping the steroid. PMID- 1440851 TI - The occurrence of cytotoxic and non-complement-fixing antibodies in the crossmatch serum of patients with early acute rejection episodes. AB - In an earlier study we found a strong correlation between the presence of donor reactive HLA-specific antibodies in the crossmatch serum and early acute rejection episodes. Our experience was also that some of these antibodies were not cytotoxic and could therefore not be detected using the microcytotoxicity assays. In the present study, 11 patients from the earlier study who had weakly positive B cell reactive cytotoxic antibodies of the IgG class were further characterized. In addition, 14 new patients were selected who experienced early acute rejections but had a completely negative donor-B cell cytotoxicity crossmatch. A group of 12 controls without immunological complications was added, as well as 5 patients with early graft losses due to nonimmunological causes. Using the flow cytometric crossmatch test we confirmed the presence of HLA specific antibodies in all 11 patients from the earlier study. In addition, positive flow cytometric crossmatches shown to be caused by HLA antibodies were observed in 11 of the 14 patients with acute rejections and negative cytotoxic crossmatch. One of 17 control patients had antibodies that were not HLA-reactive. IgA antibodies as well as IgG subclass determinations were performed in all positive sera. A substantial proportion of patients had HLA-specific antibodies of non-complement-binding classes (IgG2, IgG4, IgA) often of higher titers than IgG1 and IgG3. The subclass distribution pattern was heterogeneous and often included several subclasses. We conclude that non-complement-fixing antibodies can also contribute to the risk for development of early acute rejections after necrokidney transplantation. Immunological mechanisms for these findings are discussed. PMID- 1440852 TI - Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody. AB - Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival. PMID- 1440853 TI - Acute vascular rejection in renal transplantation--diagnosis and outcome. AB - Thirty episodes of histologically verified acute vascular rejection in kidney transplant recipients were studied. In 11 grafts the rejection was mainly vascular, whereas in 19 grafts a concomitant cellular rejection was seen. Histological features prognostic for bad outcome were glomerular necrosis and thrombi in the arteries and arterioles. Characteristic findings in transplant cytology, i.e., high number of monocytes and low number of lymphocytes and blast cells were noted prior to the onset of clinical signs of rejection, and this finding was also persisting throughout the rejection episode. The numbers of lymphocytes and blast cells were significantly lower in grafts with a pure vascular rejection than in grafts with a concomitant cellular rejection. Vascular rejection was reversible in 15 cases. As rescue therapy plasmapheresis and added immunosuppression were often successful. PMID- 1440854 TI - Noninvasive procedures for diagnosis of renovascular hypertension in renal transplant recipients--a prospective analysis. AB - The purpose of this study was to clarify the selectivity and specificity of noninvasive procedures for diagnosis of clinically suspected posttransplant renovascular hypertension. We prospectively investigated 25 renal transplant recipients with arterial hypertension and clinically suspected stenosis of the graft artery (8 female and 17 male patients; ages 45 +/- 15 years). We performed a captopril test with 25 mg captopril (n = 25), renography with technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) before and after angiotensin converting enzyme (ACE) inhibition with determination of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) (n = 23) and color-coded duplex ultrasonography of the transplant kidney vessels (n = 24). Renal transplant artery stenosis (RTAS) was excluded by renal arteriography in 20 patients and by operative evaluation or clinical follow-up in 5 patients. We identified 4 patients with RTAS and renovascular hypertension. The noninvasive methods showed the following results (sensitivity/specificity): (1) captopril test: 75%/67%; (2) renography combined with ACE-inhibition: 75%/84%; and (3) color-coded duplex ultrasonography: 100%/75%. We conclude that in patients with clinical evidence of RTAS most noninvasive diagnostic procedures are not sufficiently accurate to exclude the diagnosis. Only color-coded duplex ultrasonography did not fail to detect all patients with RTAS and may act as a screening test. Intraarterial renal angiography remains the most reliable and as-yet indispensable diagnostic test for transplant recipients to rule out RTAS. PMID- 1440855 TI - The effects of steroid withdrawal on the lipoprotein profiles of cyclosporine treated kidney and kidney-pancreas transplant recipients. AB - Lipoprotein profiles were measured before and two months after complete withdrawal of prednisone in 34 kidney and 9 kidney-pancreas transplant recipients subsequently maintained on cyclosporine and azathioprine. Withdrawal of steroid therapy was accompanied by a 17% reduction in total serum cholesterol levels. However, there was a parallel reduction in all other measured lipoprotein concentrations, including an 18% reduction in high-density lipoprotein cholesterol levels. In diabetic recipients of a kidney or kidney-pancreas transplant, the ratio of total to high-density lipoprotein cholesterol was unchanged after steroid withdrawal. In nondiabetic kidney transplant recipients, this ratio actually increased significantly following withdrawal of prednisone. These observations suggest that it is premature to presume that withdrawal of steroid therapy will reduce the cardiovascular risk related to hyperlipidemia in cyclosporine-treated kidney or kidney-pancreas transplant recipients. PMID- 1440856 TI - Cyclosporine nephrotoxicity in lung transplant recipients. AB - End-stage lung disease has been treated successfully by lung transplantation (LTXP) at our institution since 1983. We report on the renal function of 30 LTXP recipients who were followed for at least 6 months (mean, 39 months; range, 6-60 months). All patients received quadruple immunosuppressive therapy including cyclosporine A, with a trough serum level (RIA) between 150 and 250 ng/ml for the first 6 months between 125 and 150 mg/ml after 6 months. The mean serum creatinine (SeCr) increased from a baseline value of 75 +/- 3.5 to 182 +/- 13.9 microM at the end of the follow-up. The greatest change in SeCr occurred within the first 6 months post LTXP. Fifteen of 30 patients who were initially normotensive required at least one antihypertensive medication post LTXP. By the end of the follow-up, 9 patients had SeCr > 200 microM. Two patients in this institution have progressed to end-stage renal disease requiring dialytic therapy. CsA nephrotoxicity has emerged as a major source of morbidity in the lung transplant population. Nephrotoxicity occurs early, and there does not appear to be any trend toward reversibility despite a lowering of the dose. Renal parenchymal injury may be progressive, despite an apparent plateau of the SeCr in some patients. PMID- 1440857 TI - Immunofluorescent localization and immunochemical determination of cyclophilin-A with specific rabbit antisera. AB - We raised rabbit antisera against homogeneous bovine cyclophilin A (CypA) and we report their use for its immunofluorescent and immunochemical detection without resorting to cyclosporine binding. Indirect immunofluorescence demonstrated that in tissue culture cells CypA is present in the cytoplasm diffusely and also associated with vesicles and the Golgi apparatus. In mitotic cells CypA is increased in amount and redistributed away from cytoplasmic organelles. High levels of CypA were demonstrated in murine splenic erythroblasts and myeloblasts, but they became undetectable during differentiation to mature erythrocytes and granulocytes. Large, often granular, lymphocytes stained very intensely, but small lymphocytes demonstrated variable staining. Dot blot immunoassays demonstrated that murine tissues contain similar amounts of CypA. During CsA treatment murine liver can increase its CypA content much more than spleen. In summary, we demonstrated that cells known to be resistant to the effects of CsA have high levels of CypA. Also tissues that are resistant to CsA can increase their levels more than sensitive tissues upon CsA exposure. Taken together these results suggest that CypA plays a role in cell cycle progression and that sensitivity to CsA may not be simply a reflection of the baseline CypA levels, but may also be affected by the regulation of these levels. Further work is needed in order to delineate the role of CypA in the cell cycle and its relation to the action of CsA. PMID- 1440858 TI - Patterns of T cell-accessory cell interaction in the generation of primary alloresponses in the pig. AB - Partially inbred, MHC-homozygous miniature swine provide a unique model for the study of organ transplantation and the induction of tolerance in large animals. Models of both vascularized solid organ transplantation and bone marrow transplantation have previously been established. The availability of monoclonal antibodies reactive with porcine leukocyte subset antigens now makes possible studies of the cellular immunology in this species, affording the opportunity to examine mechanisms of transplant tolerance and graft rejection in increasing detail. Using such antibodies and peripheral blood leukocytes from pigs of recombinant MHC haplotypes, we have examined porcine T cell-accessory cell interactions in vitro with attention to T cell subsets and the class of MHC alloantigen stimulation. Primary allospecific MLR and CML cultures were studied after depletion of accessory cells from responder and/or stimulator populations. Although class II MHC antigens were expressed on the majority of porcine T cells before and after depletion, these cells were insufficient for antigen presentation, since there was an absolute requirement for ACs in the generation of primary alloresponses. Proliferative and CTL alloresponses could be generated provided that ACs of either stimulator or responder type were present. Selective depletion of CD4+ T cells from the responder population demonstrated: (a) that the interaction mediated by self ACs was CD4-dependent; (b) that two pathways exist for interaction involving allogeneic ACs; and (c) that the interaction involving allogeneic class II is CD4-dependent, while that with allogeneic class I is not. PMID- 1440859 TI - Priming and cross-priming for H-Y in female mice. AB - Although female mice (H-2b and H-2g) that are responders to H-Y are able to cross prime for this antigen, their ability to do so varies from strain to strain and can be influenced by whether they are exposed to H-Y via a subcutaneous hind footpad inoculation of male cells or via a male skin graft. On the other hand, females (H-2k) that are low responders to H-Y only can be sensitized to male skin isografts following a hind footpad inoculation of syngeneic male cells. PMID- 1440860 TI - Determination of tolerance to self E alpha peptides by clonal elimination of H-2E reactive T cells and antigen presentation by H-2A molecules. AB - A series of three synthetic peptides spanning H-2E alpha k chain residues (90 110), (110-130), and (130-150) were synthesized and purified. Mice representative of H-2E- (B6, B10, B10.M, B10.Q, B10.S) and H-2E+ (B10.D2, B10.K, B10.RIII) were immunized with individual peptides and lymph node cells challenged in vitro. Both B6 and B10 mice respond to in vitro challenge to peptides (90-110) (cpm 20,000), (110-130) (cpm 40,000), and (130-150) (cpm 60,000). In contrast all H-2E+ haplotypes were unresponsive to all three peptides (cpms < 10,000). Furthermore, B10 mice could be rendered hyporesponsive to E alpha k peptide challenge following expression of an E alpha k transgene or mating to an H-2E+ strain. The H-2Ad,k,f,q,s alleles were associated with reduced peptide recognition. Furthermore, alteration of the H-2A beta chain in bm12 mutant mice resulted in impaired responses to all three peptides. Immunization with synthetic peptides comprising major histocompatibility molecules may yield insights into mechanisms of self-tolerance. PMID- 1440862 TI - Successful reversal of hyperacute renal allograft rejection with the anti-CD3 monoclonal OKT3. PMID- 1440861 TI - Living kidney donor and recipient evaluation in Fabry's disease. PMID- 1440863 TI - Bone marrow dysfunction after liver transplantation for fulminant non-A, non-B hepatitis. High risk for young patients. PMID- 1440864 TI - Liver transplantation for hereditary tyrosinemia--early transplantation following the patient's stabilization. PMID- 1440865 TI - The use of transesophageal ultrasonography for the diagnosis of inferior vena caval outflow obstruction during liver transplantation. PMID- 1440866 TI - The effect of the prostaglandin analogues misoprostil and enisoprost on the synergy between donor-specific transfusion and cyclosporine in allograft survival. PMID- 1440867 TI - Evidence of the central role of the thymus in the induction of donor-specific unresponsiveness to a renal allograft. PMID- 1440868 TI - Succinyl acetone plus methotrexate as graft-versus-host disease prophylaxis in DLA-haploidentical canine littermate marrow grafts. PMID- 1440869 TI - HLA-mismatched bone marrow transplantation. PMID- 1440870 TI - New insights into the mechanism of HIV-1 trans-activation. PMID- 1440871 TI - Preparation of high molecular weight DNA from Drosophila adults for PFGE analysis. PMID- 1440872 TI - Reprobing of DNA:DNA in situ hybridization preparations. PMID- 1440873 TI - Eukaryotic replication origins as promoters of bidirectional DNA synthesis. AB - Recent work in yeast shows that eukaryotic origins of DNA replication are multipartite regulatory elements resembling promoters of transcription. As for the regulation of transcription, accessory transcription factors appear to function in concert with basic origin recognition factors to regulate initiation of DNA synthesis at specific subsets of origins. The participation of transcription factors in the regulation of DNA replication may facilitate temporal control of transcription and replication during the cell cycle, as well as providing a mechanism for integrating origin selection with the cellular transcriptional program. PMID- 1440874 TI - The S locus of flowering plants: when self-rejection is self-interest. AB - In certain families of flowering plants, a self-incompatibility (SI) locus prevents self-fertilization, by a specific interaction between the S-gene product produced in the pistil and the S-gene products borne on or expressed by the male gametophyte, the pollen grain. The female S-locus gene products for two families showing different types of SI have been putatively identified as major pistil glycoproteins (the S-locus-specific glycoproteins of the Brassicaceae and the S RNases of the Solanaceae). However, they are distinct in sequence and mode of action. The nature of the S-locus gene product borne by the pollen is still uncertain in both systems. PMID- 1440875 TI - Dopamine: from Cinderella to Holy Grail. PMID- 1440876 TI - Regulation of brain neurotrophin expression by physiological activity. PMID- 1440877 TI - Development of GPIIb/IIIa antagonists as antithrombotic drugs. AB - Thrombosis represents a major target for development of drugs to prevent and treat a variety of cardiovascular and cerebrovascular diseases, which are the leading cause of morbidity and mortality in the Western world. This review by Andy Nichols and colleagues focuses on a central process in thrombosis, namely platelet aggregation, and how it can be inhibited by antagonists of the adhesion molecule GPIIb/IIIa. Successful and future therapeutic applications of GPIIb/IIIa antagonists, and their pharmacology, are considered in detail. PMID- 1440878 TI - Health information and training materials for developing countries. PMID- 1440879 TI - An approach to the management of tuberculosis in HIV endemic areas. AB - The epidemic of HIV-associated tuberculosis is having a severe impact on tuberculosis control in sub-Saharan Africa, as well as the United States of America, and is expected to spread. Where facilities are limited, the association between HIV and sputum-smear negative tuberculosis hampers diagnosis; trials of anti-tuberculous therapy are indicated in some cases. Standard treatment regimens are effective, but thiacetazone should be avoided because of its association with severe, cutaneous adverse reactions. Treatment may have to be prolonged in HIV positive cases. Measures to maximize compliance with therapy are paramount. These include the use of the shortest possible regimens, of recognized potency, and emphasis on ensuring that the regimen is understood by and readily accessible to the patient. PMID- 1440880 TI - How many bloods will a 'HIVCHEK' check? Multiple tests for HIV antibody for a single screening kit. AB - Detection of HIV infection in blood donors or populations is usually by testing sera for antibodies to HIV-1 and HIV-2. Screening tests are now highly sensitive and specific, but still expensive and scarce in Africa. We tested the commercially available kits 'HIVCHEK 1 + 2' in two field laboratories, on specimens from blood donors and antenatal women in rural Zaire. We describe a method of using one test kit for up to five serum samples, saving money and time. In 491 antenatal mothers in Eastern Zaire, among whom the HIV seroprevalence was 3.3%, we compared 'HIVCHEK' results with results obtained by ELISA and Western blot. The 'HIVCHEK' multiple-sample method had a sensitivity of 82% and a specificity of 99.6%. In an area with an HIV seroprevalence of < 4%, using 'HIVCHEK' by the multiple sample method would lead to a saving of about 2,400 pounds for every 1000 individuals tested. PMID- 1440882 TI - Bacteriology of snakebite abscess. AB - Thirty-eight cases of abscess secondary to pit viper envenomation are reviewed. The incidence of abscess formation was 9%. Results of aerobic cultures revealed growth of enteric, coliform organisms in 22 of 25 isolates obtained from previously unopened abscesses. Clinical evidence for co-existent anaerobic infection is presented. No cases of tetanus were encountered. Clinical and laboratory findings of patients in the study are correlated with a review of bacteriologic investigations of the oral flora of venomous snakes. Use of antibiotics effective against aerobic coliforms and histotoxic anaerobic organisms for prophylaxis and/or treatment of infectious complications of pit viper envenomation are recommended. PMID- 1440881 TI - Aluminium phosphide poisoning. AB - Aluminium phosphide is a solid fumigant pesticide widely used in the Indian subcontinent as a grain preservative. Over the last 5 years there has been a dramatic increase in the number of cases of aluminium phosphide poisoning in India. Ninety-two patients with aluminium phosphide poisoning due to ingestion were studied over a period of 3 years. Abdominal pain, vomiting and restlessness were the common initial features followed by alteration in sensorium and shock unresponsive to conventional treatment. Electrocardiographic abnormalities were very common and highly variable. Routine serum biochemistry was usually unremarkable. Severe metabolic acidosis was common and mortality high (49%). The survivors recover completely without any residual organ damage. There is no known antidote. PMID- 1440883 TI - A simple scheme to improve compliance in patients taking tuberculosis medication. AB - Compliance with prescribed treatment remains a major problem in the control of tuberculosis worldwide. We describe a simple method of improving patient compliance with hospital-based treatment. Eighty-two patients paid a deposit at the start of their treatment which entitled them to cheaper drugs and was refundable on completion of the prescribed course. Sixty-two per cent of patients completed the course compared with 23% of retrospective controls. A direct relationship was found between the amount of deposit paid and the rate of completion. Reasons why poor patients (who paid a lower deposit) may default are discussed, as are the merits of short-course drug regimens. It is recommended that similar schemes be assessed elsewhere. PMID- 1440884 TI - Drug of the month: ivermectin. PMID- 1440885 TI - Treatment of scabies in rural east Africa--a comparative study of two regimens. AB - Scabies is endemic in Africa where living conditions make synchronous treatment of every member of the large extended family impossible. An open study was designed to investigate the optimum treatment of school children in rural Tanzania. In one school where 34 children (7%) were infested, treatment with benzyl benzoate was distributed to the affected child and those sleeping in close proximity. In another school where 29 pupils (6.4%) were affected, the above treatment was given along with soap and some scabicidal ointment (6% sulphur) to be used on residually affected areas. Again, the treatment was given to those sleeping in proximity. One month later 46% were clear at the first school and a significantly higher proportion (69%) at the second. I conclude that inefficient application of scabicidal treatment and lack of washing contribute to scabies treatment failures. Synchronous treatment of small groups within the extended family can be effective. PMID- 1440886 TI - Sonographic changes following splenectomy for portal hypertension in Schistosoma mansoni. AB - Eleven patients with portal hypertension due to infection with Schistosoma mansoni underwent splenectomy and devascularization operations. The patients were examined with ultrasound once preoperatively and twice postoperatively over a period of about 6 months. Following surgery there was significant and sequential reduction in the diameter of the portal vein at the hilum and the splenic vein at the pancreas. The liver lengths and index of liver size did not change significantly. No changes in the degree of periportal fibrosis could be detected. PMID- 1440887 TI - Myths and beliefs about diseases of ear, nose and throat. PMID- 1440888 TI - Is the WHO weight for age chart appropriate for infants of the developing world? PMID- 1440889 TI - Multi-resistant typhoid fever in Nepal. PMID- 1440890 TI - Phenytoin and wound healing. PMID- 1440891 TI - Family planning: KAP among rural women in Kabarole District, Uganda. PMID- 1440893 TI - A simple method for measuring nasal patency in children. PMID- 1440892 TI - Attitudes to hearing aid use in Nigerian patients. PMID- 1440894 TI - Reduction in perinatal mortality. PMID- 1440895 TI - Helicobacter pylori and non-ulcer dyspepsia. PMID- 1440896 TI - Unwanted pregnancy. PMID- 1440897 TI - Anorectal fistulae and pulmonary tuberculosis in Ibadan. PMID- 1440898 TI - Living retained second twin 6 days after first. PMID- 1440899 TI - Use of activated charcoal to treat poisoning. PMID- 1440900 TI - Inexpensive low vision aids. PMID- 1440901 TI - Reduction of complete rectal prolapse. PMID- 1440902 TI - Surgery for duodenal ulcer in Zambia. PMID- 1440903 TI - The pattern of surgical thyroid diseases in Zambia. PMID- 1440904 TI - Neonatal chlamydial conjunctivitis in Barbados. PMID- 1440905 TI - Aldehyde test (Formol-Gel test) in the diagnosis of kala-azar (visceral leishmaniasis). PMID- 1440906 TI - A bilharzioma in association with HIV disease. PMID- 1440907 TI - A rare presentation of hydatid disease of liver. PMID- 1440908 TI - An unusual echographic appearance of the spleen in tuberculosis. PMID- 1440909 TI - Echinococcus breast abscess. PMID- 1440910 TI - [Cytogenetic effect in peripheral blood lymphocytes of children living in villages in the Ovruch District, Zhitomir Region of the Ukraine contaminated by radionuclides]. AB - For the purpose of genetic indication of low level of chronic radiation exposure the cytogenetic monitoring of some critical children groups living in two contaminated Ukrainian villages was carried out. In all the groups the mean frequency of aberrant cells and chromosome type aberrations (including dicentrics, centric rings, chromosome translocations as well as polyploid cells) significantly exceeded control level. During the repeated examination of children from Vistupovichi (in 13 months after the first one) the striking increase of cytogenetic effect was revealed. Dicentrics and rings were registered in 79% of persons with the individual rate 0.5-1.5 and mean group frequency 0.57 per 100 cells. The authors tried to evaluate the average cumulative doses of radiation for examined groups using G. Littlefield equation for dicentric outcome under the low dose rate Cs-137 source and taking into account the assumption about the reducing of 50% dicentrics per year. According to this rough calculation, the revealed cytogenetic effect can correspond to the mean total dose of 33 cSv for Vistupovichi children. PMID- 1440911 TI - [Genetic monitoring in connection with the Chernobyl accident]. AB - The complex investigation has been provided to control the genetically influenced processes after Chernobyl accident in some Ukrainian regions. Some dangerous trends in genetic populational status were revealed in the Ukrainian regions surrounding Chernobyl power plant allowing for the increasing number of congenital anomalies among the newborns and the spontaneous abortions as well as higher proportion in aberrations of chromosome type in human somatic and embryos cells, higher incidence of structural defects in embryonal bone system and higher, compared with control, proportion of children with intensive catabolism (R-protein homeostasis). PMID- 1440912 TI - [Cytogenetic study of the chorion and placenta in prenatal diagnosis of fetal pathology]. AB - The experience of investigation of 230 chorion and placental biopsy in 209 women of high risk pregnancy group is presented. Two methods of "direct" chromosomal analysis have been compared. Prospects and high economic efficiency of chorion and placenta studies as against other methods of prenatal diagnosis, great role in a decrease of prenatal disease and mortality are confirmed. PMID- 1440913 TI - [Results of the morphologic examination of abortuses and features of the pregnancy course when it is aborted in trimesters I and II]. AB - Morphologic examination of abortuses has been carried out in the women, whose pregnancy proceeded under the threat of abortion. While analyzing the course of pregnancy and comparing with the results of the pathoanatomic examination, it is concluded that prenatal diagnosis is necessary in connection with the high risk of congenital developmental defects under the threat of abortion. PMID- 1440914 TI - [Problems of medical genetics in the Ukraine]. PMID- 1440915 TI - [Clinical and genetic analysis of the Townes-Brocks syndrome]. AB - Due to the performed analysis of data from literature and the author's observations of the Taunse-Brock's syndrome a wide variability of phenotypic manifestations is shown, the diagnostic criteria of syndrome are determined, its autosomic-dominant inheritance with complete penetrance is confirmed. PMID- 1440916 TI - [Electron microscopic and histochemical examination of hepatocytes in rat embryos exposed to the effect of a static electric field]. AB - Static electric field with intensity of 150-80 V/cm has no teratogenic and embryolethal effect on the rat embryos. However, it provokes disturbance of the morphofunctional state of embryo liver, causes destructive-dystrophic changes in the parenchyma cells, decreases the content of nucleic acids, induces disturbances of the membrane systems of mitochondria and other cell structures. PMID- 1440917 TI - [Deviations in progeny development of rats expressing the human growth hormone gene]. PMID- 1440918 TI - [Quantitative characteristics of heterochromatin regions in human metaphase chromosomes at different stages of ontogenesis]. AB - The comparative study of C-heterochromatic regions has been provided for 1, 9, 16 and Y chromosomes of 30 human embryonal in vivo lymphocytes of 6-8 gestational weeks (obtained with medical abortions), on the one hand, and in vitro lymphocytes of 100 phenotypically normal newborns, on the other hand. According to the results the heterochromatic regions of 1, 9 and Y are significantly shorter in embryonal chromosomes as compared with lymphocytes of newborns. PMID- 1440919 TI - [Value of molecular-genetic examination of patients with the Shereshevsky-Terner syndrome and married couples with disorders of reproductive function]. AB - The molecular-cytogenetic investigation gives a significant opportunity for diagnosis of gonosome mosaics. Due to the molecular-cytogenetic method additional chromosomes in karyotypes in 4 of 13 patients are determined. A significant spreading of mosaicism type 45, XO/46, X among women with early spontaneous abortions is revealed. PMID- 1440920 TI - [Screening of mentally retarded persons for "fragile" X-chromosome]. AB - 112 mentally weak persons aged from 2 to 18 with different degree of oligophrenia have been examined. Cultivation of blood lymphocytes was performed on medium 199 containing 5% of cattle serum. 9 persons with "fragile" X-chromosome are revealed. High frequency of autosomes fragility among the examined contingent of patients is found. A supposition is advanced on interrelation between homozygosity of "fragile" parts of autosomes and oligophrenia. PMID- 1440921 TI - [Successes and prospects of molecular diagnosis of the most widespread inherited diseases]. AB - Current state of molecular diagnosis of hereditary diseases most common in the former USSR such as cystic fibrosis, Duchenne muscular dystrophy, haemophilia A and B as well as phenylketonuria is reviewed. Basic results of prenatal diagnosis and carrier detection of the above mentioned diseases in St.-Petersbourg and somewhere else in Russia are presented. The urgent necessity to start an efficient molecular diagnosis of some other widespread hereditary diseases (von Willebrand's disease, Martin-Bell syndrome, polycystic kidney. Huntington chorea, myotonic dystrophy, etc.) is emphasized. Creation of new diagnostic centers dealing with most common diseases as well as complementing each other as to molecular diagnosis of more rare hereditary diseases is substantiated. Prospects of implementation of new molecular methods and novel technical approaches (preimplantation embryos, fetal cells selected from maternal blood) for more efficient diagnosis of hereditary diseases are briefly outlined. PMID- 1440922 TI - [Attempt at quantitative estimation of genetic effects of chemical pollution of atmospheric air in urban populations]. AB - Epidemiological investigation of spontaneous abortions and congenital anomalies in three towns of Ukraine has shown that mutation rate in Mariupol, the most contaminated town, as compared with relatively clean town is essentially higher. Genetical consequences due to environmental chemical pollution in Mariupol proved to be equivalent to the chronic influence of ionizing radiation for 30 years in the dose of 230 REM. PMID- 1440923 TI - [Urgent problems of elimination of medical aftereffects of the Chernobyl nuclear reactor accident]. PMID- 1440924 TI - [The Chernobyl project]. PMID- 1440926 TI - [The dependence of the incidence of encountering cells with micronuclei in the experimental metastases of rat rhabdomyosarcoma on the duration of the growth and on the size of these metastases]. AB - Cell suspensions of rat transplantable rhabdomyosarcoma RA-2 were injected to white rats. The experimentally induced lung metastases (ELM) were estimated according to the frequency of micronucleated cells (MNC) that appeared 9-20 days after injection (a. i.). The frequency of MNC in ELM decreased from 2.7% (9 days a. i.) to 0.7% (20 days a. i.). The ELM which were of the same size but were examined at different time after injection had equal frequencies of MNC. At each investigated time after injection the least frequencies of MNC were observed in the ELV of the biggest size. The data provided allow to infer that the growth time and site of ELM may influence the spontaneous karyotype instability rates. PMID- 1440925 TI - [Myocyte polyploidy in human cardiac pathology]. AB - With general atherosclerosis, the ploidy of left ventricle myocytes in the hearts of patients that underwent infarction corresponds to the norm variation irrespective of the ventricle and heart weights. At heart diseases the myocyte nucleus ploidy is often much higher than the norm variability both in hypertrophied ventricles and in those with normal weight. An additional polyploidization is suggested that may occur at some natural ontogenetic periods of human development (in the childhood) during heart diseases both innate or spontaneously appearing at the particular time. Unlike, the myocardial hypertrophy in adults does not stimulate myocyte polyploidy. PMID- 1440927 TI - [Tubular structures in Mycoplasma gallisepticum and the localization of a tubulin like protein]. AB - In all the strains of M. gallisepticum investigated, a protein with apparent molecular weight 40 kDa was revealed by immunoblotting with polyclonal anti-calf brain tubulin antibodies and monoclonal anti-chicken alpha-tubulin antibodies. In other 8 investigated Mycoplasma species no positive reactions with the same antibodies were found. The M. Gallisepticum cells were examined under electron microscope on fine serial sections and on some sections going at different angles to the long cell axis. Undermembrane system of tubules was revealed and the intracellular pattern of the tubular structures were reconstructed. The immunoelectron microscopic data suggest that tubulin-like protein may be included into the structures. PMID- 1440928 TI - [A comparative analysis of the action of oxidative metabolic inhibitors on the luminescence parameters of normal and tumorous cells]. AB - Comparative investigation of different mitochondrial oxidative metabolism inhibitors action on NAD(P)H and flavoproteins fluorescence intensity of minimal transformed 3T3 NIH mouse fibroblasts and rat HTC hepatoma cells was made. Principle differences were shown between these cells in oxidized flavoproteins fluorescence intensity changes under the action of used inhibitors. It is suggested that the unusual HTC hepatoma cells flavin fluorescence intensity increase is connected with the oxidation of unidentified flavin-containing component functionally attached to mitochondrial respiratory chain. PMID- 1440929 TI - [The effect of antithymocyte serum on the natural cytotoxicity of C3HA mouse splenocytes in the early periods after 20-methylcholanthrene administration]. AB - The role of T-lymphocytes in natural cytotoxicity of splenocytes of C3HA mice after a single injection of 20-methylcholanthrene (20-MC) was investigated. A splenocyte suspension was treated with anti-T-cell serum and complement. This treatment was not shown to exert influence on the natural cytotoxicity of splenocytes within 1-13 days after injecting 20-MC. PMID- 1440930 TI - [The use of an immunohistochemical method for detecting N7-methylguanine in human cells]. AB - An immunohistochemical method, followed by silvering (Ag-treatment) of the final product of peroxidase reaction for N7-methylguanine detection, was first employed for human cells treated in vitro with N-methylnitrosourea. This method appeared to be highly specific and sensitive, compared to the routine immunohistochemical technique. Evidence has been provided on the application of Ag-treatment for detecting N7-methylguanine in the esophagus epithelium of patients with a high risk of cancer with this particular locality. PMID- 1440931 TI - [Increasing the sensitivity of an immunohistochemical method for detecting carcinogen adducts with DNA]. AB - Application of polyclonal antibodies against N7-methylguanine (N7-MG) for immunohistochemical detection of the DNA damage following exposure to methylnitrosourea in cultured cells (CHO and IAR-27) has been shown. The approaches were applied: a) an extraction of nuclei, and b) a silver intensification of the end product of peroxidase reaction. Both the approaches were effective in increasing the sensitivity of immunohistochemical detection of N7-MG, the latter technique being most sensitive. It is proposed that the silver intensification technique is very perspective to have a high levels of sensitivity and specificity, a sufficient contrast and preservation of the cell morphology. The efficiency of the new approach in application to the purposes of molecular epidemiology is discussed. PMID- 1440932 TI - [The mitotic cycle and DNA repair in UV-irradiated murine neuroblastoma cells]. AB - A correlation has been shown between a reduced rate of movement of UV-irradiated neuroblastoma cells from G1 into S phase, an essential increase of cells in S phase while progressing through the cell cycle, and a defect in free DNA synthesis on a damaged template. These indices may reflect one and the same cell response to the UV light. PMID- 1440933 TI - [The effect of 3-aminobenzamide on the mitotic cycle of Chinese hamster cells cultured on a medium with 5-bromodeoxyuridine following ionizing radiation action]. AB - A specific inhibitor of poly(ADP-ribose)polymerase-3-aminobenzamide (6 mM) has been shown to: 1) reduce survival of non-irradiated CHO-K1 cells, cultivated in medium containing 5-bromodeoxyuridine (10 mkM, BDU cells), and increase their radiosensitivity; 2) induce G2 delay in BDU cells while progressing through the cell cycle as analysed by the DNA flow cytometry; 3) increase to a great degree G2 delay in X-irradiated BDU cells. 3-Aminobenzamide is primarily effective when it is present during the first or two first cell cycles after the initial addition of BDU. The above data confirm the involvement, presumably an indirect one, of ADP-ribosylation in the DNA repair through affecting the chromatin structure. PMID- 1440934 TI - [The effect of Mycoplasma contamination on the karyotypic structure of a skin fibroblast cell line from the Indian muntjac]. AB - The karyotypic variability has been studied in a low chromosomal cell line of the Indian muntjak skin fibroblasts contaminated with Mycoplasma arginini R-16 and Acholeplasma laidlawii A. The mycoplasmal contamination exerted influence on the cell distribution for the chromosome number. The frequency of the modal class cells with 7 chromosomes, having the main structure variant of the karyotype (MSVK) 2 + 2 + 1 + 1 + 1, was seen to decrease, while the frequency of the submodal class cells with 6 chromosomes, having MSVK 2 + 2 + 1 + 1 because of the loss of Y1 chromosome from MSVK 2 + 2 + 1 + 1, to increase. The frequency of chromosomal aberrations, predominantly that of dicentrics, was higher in the contaminated variants. Dicentrics were mainly produced by chromosomes 1 and 2. They were formed by a nonrandom combination of chromosomes and their arms. Possible correlations are discussed between aneuploidy and dicentric chromosome formation in low chromosomal cell lines, and cell adaptations to culture conditions. PMID- 1440935 TI - [The cellular mechanism for the formation of lamellar bodies in type-II pneumocytes in rat lungs]. AB - Pneumocyte type II cells from lungs of native rats and of rats that inspired a hypoxic mixture of gases were investigated by transmission electron microscopy. In cells of experimental rats, membrane structures were found that well compare with lamellar bodies. Experimental results and analysis of literature allowed to put forward a hypothesis about the cell mechanism of formation of lamellar bodies from the spiral twisted membranes of the endoplasmic reticulum. PMID- 1440936 TI - Consensus development conference: assessment of the quality of life in cancer clinical trials. Italian Psycho-Oncology Society (SIPO). PMID- 1440937 TI - Plasma steroid transport in subjects with tumors of hormonal target organs: a review. AB - Tumors derived from a hormonal target organ are assumed to be stimulated by the same hormone that stimulates the normal target tissue. In spite of attempts to acquire direct indications of a correlation between hormones and cancer, none have been definitive because studies of total and free hormone levels have given contradictory results. For this reason, attention has shifted to the study of plasma binding and transport of hormones, that is, of the proteins responsible for modulation of the hormone effect and thus of hormone bioavailability. The data reviewed indicate that in-depth study of the transport and binding system of sex steroids would give new information about the endocrine characteristics of cancer patients. PMID- 1440938 TI - The effects of the macrocyclic lactone bryostatin-1 on leukemic cells in vitro. AB - The macrocyclic lactone bryostatin-1 was found to exert in vitro antineoplastic activity against several leukemic cell lines, including human K562 erythroleukemia, HL60 promyelocytic leukemia, REH and MOLT-4 lymphoblastic leukemias, CCRF-CEM lymphoma, KG-1 myeloid leukemia, and murine P388 lymphocytic leukemia. No statistically significant difference in sensitivity to bryostatin-1 was found between adriamycin-resistant P388 and K526 subclones and their sensitive counterparts. Freshly explanted clonogenic leukemic cells showed a variable sensitivity to bryostatin-1 in 10/12 tested samples. The IC50 of clonogenic leukemic cells was 4 x 10(-3) M bryostatin-1, and that of normal marrow CFU-GM was 10(-5) M. Leukemic cells exposed to bryostatin-1 showed a variable degree of monocytic differentiation as evaluated by ANAE staining and morphology. Bryostatin-1 is also able to inhibit the growth of CFU-GM from myelodysplastic marrow and to shorten the duration of dysplastic hematopoiesis in liquid culture. In conclusion, these data suggest that bryostatin-1 is a potent antileukemic agent in vitro that may be potentially useful for clinical studies. PMID- 1440939 TI - Effect of medroxyprogesterone acetate on immunohistochemical expression of estradiol in endometrial carcinoma. AB - The effect of medroxyprogesterone acetate (MPA) on the immunohistochemical expression of estradiol (E2) was investigated in 25 cases of endometrial carcinoma. Twenty-three cases of the endometrial carcinomas showed positive immunoreactivity for E2. The immunohistochemical expression of E2 was more intensive in carcinoma cells than in stromal cells. Although the morphologic alterations induced by MPA treatment were observed only in 2 cases who were administered more than 30,000 mg of MPA, the staining intensity in most cases appeared to decrease after the treatment. The decrease in E2 immunoreactivities of cancer cells as well as of stromal cells in Grade 1 or Grade 2 was significant. These results suggest that MPA might decrease the E2 content in endometrial carcinoma cells as well as in stromal cells. PMID- 1440940 TI - Bone marrow histopathology and prognosis in malignant lymphomas. AB - Bone marrow trephine biopsies of patients with non-Hodgkin's malignant lymphomas (ML), followed for at least 4 years, were investigated using univariate and multivariate survival analyses to detect which anagraphic data and histomorphologic medullary patterns before therapy were related to the prognosis. In 234 ML (146 low grade, 88 high grade), univariate analysis showed that survival was reduced by bone marrow involvement, absence of reactive lymphoid nodules, and low marrow cellularity. Moreover, in low-grade ML, patients 50 years or older and showing absence of myeloid hyperplasia, excess of hemosiderin and mast cell hyperplasia had significantly lower-survival rates. The prognostic relevance of these parameters did not change when cases without marrow involvement were separately analyzed. Multivariate analysis showed that, besides marrow involvement, age and myeloid hyperplasia had significant prognostic importance in low-grade ML, and lymphoid nodules in high-grade ML. Our data confirm the value of bone marrow histopathology in ML and indicate that the prognosis is related not only to medullary involvement but also to the morphology of the uninvolved marrow. PMID- 1440941 TI - Histology as a prognostic factor in early gastric cancer. AB - Of 431 patients with gastric cancer observed in our institution, 23 (5.3%) had early gastric cancer (EGC). Macroscopic presentation, histology, depth of invasion, and lymph node involvement were evaluated in all the cases. All patients underwent surgery and an intensive follow-up was performed. Five of the 23 patients progressed, and the risk factors were examined. Histology seemed to be the main prognostic factor in our study, since intestinal type of EGC was associated to a significantly better prognosis. Total gastrectomy is indicated in the proximal localization of EGC, and should perhaps be performed also in cases presenting undifferentiated histology. PMID- 1440942 TI - Minimally differentiated acute myeloid leukemia: a morphologic, cytochemical and ultrastructural study. AB - Seven of 368 cases of acute myeloid leukemia (AML) could not be subclassified by routine morphologic, cytochemical and immunologic analyses during the period January 1989 to December 1990. Further investigations including ultrastructural examination, anti-myeloperoxidase and myeloid specific antigen analysis were carried out in all these patients and they were classified as AML-MO, as per the FAB criteria. Morphologically these blasts resembled ALL-L2/AML-M1. Cytochemically they were negative for Sudan black, myeloperoxidase, periodic acid Schiff, and non-specific esterase. On initial immunophenotypic analysis, they could not be classified into B, T or myeloid lineages. Further investigations revealed CD13 and CD33 positivity in 4 of 6 patients. Anti-myeloperoxidase was positive in 6 of 6 patients and ultrastructural examination revealed myeloperoxidase-positive blasts in 6 of 7 cases. Cytogenetic analysis done in one patient revealed 60% abnormal metaphases. Six of 7 cases were treated with aggressive chemotherapy. One patient achieved complete remission but relapsed after 6 months, whereas others were resistant to treatment. Hence we conclude that an aggressive investigative and therapeutic approach is required to identify and treat AML-MO. PMID- 1440943 TI - Ultrastructural modifications in one case of hairy cell leukemia during alpha interferon therapy. AB - There are many reports concerning the morphology of hairy cell leukemia (HCL), but, to our knowledge, there are no data on the ultrastructural modifications of HCL during interferon therapy. The ultrastructural modifications of neoplastic cells in peripheral blood in a case of HCL were investigated before and 2 and 4 months after beginning treatment with human lymphoblastoid alpha-interferon. Before therapy, hairy cells displayed the typical cytoplasmic projections, and 4% contained ribosome-lamellae complexes (RLC) (the cells contained up to 7 RLC). Two months from the beginning of therapy, hairy cells had shorter projections, RLC had disappeared, and tubuloreticular structures (TRS) had appeared in 2.2% of the elements. Four months from the beginning of therapy, TRS persisted in 2.3% of hairy cells, cylindrical confronting cisternae (CCC) appeared in 6.8% of the cells, and uncommon RLC, in close contact with the rough endoplasmic reticulum and nuclear membrane, were found in 1.5% of the elements. The cells contained up to 3 RLC. Our data confirm that interferon stimulates the synthesis of TRS and CCC, whereas the reappearance of uncommon forms of RLC could reflect their neosynthesis, possibly related to the interferon therapy. The frequent findings of a close contact between RLC and nuclear membrane support the view that RLC are derived not only from rough endoplasmic reticulum, but also from the nuclear membrane. PMID- 1440944 TI - Cationic content in multiple mammary cysts. AB - One hundred and ninety-six breast cyst fluid samples from 78 consecutive patients with multiple cysts were subdivided according to the K+/Na+ ratio: type 1 (K+/Na+ ratio > 1) and type 2 (K+/Na+ ratio < or = 1). Cysts of the same type were found in 57.7% of patients (concordant group). Such a finding suggests that in patients bearing multiple cysts, all aspirated fluids need to be classified on the basis of their cationic composition. In the concordant group, type 1 cysts were more frequent than in the discordant group (80.3% vs 59.5%, P = 0.002). High K+/Na+ ratios (> 4.0) were present in 64% of type 1 cysts in the concordant group compared to 37.7% in the discordant group (P = 0.001), which suggests a different activity of the epithelium lining the cyst wall. PMID- 1440945 TI - Osteosarcoma of the extremity metastatic at presentation: results achieved in 26 patients treated with combined therapy (primary chemotherapy followed by simultaneous resection of the primary and metastatic lesions). AB - From September 1986 to December 1989, 26 selected patients with high-grade osteosarcoma of the extremities metastatic at presentation were treated with primary chemotherapy (high doses of methotrexate, -cisplatinum and adriamycin) followed by surgery. Twenty-one cases underwent resections of the primary and metastatic tumor at the same time; owing to the disappearance of lung metastases after preoperative chemotherapy in 3 cases, only the primary tumor was operated on. Due to progression of the disease in 2 patients, no surgery was performed. Histologic examination of the resected specimen was performed to evaluate the percentage of necrosis produced by chemotherapy on the primary and metastatic tumor. After surgery, the patients received further chemotherapy with the same drugs used preoperatively plus ifosfamide and VP-16. The histologic response of the primary tumor was good (> 90% tumor necrosis) in 25% of the cases; in the resected metastatic nodules, 23% had good responses. A discrepancy between the histologic response of the primary and secondary tumor was observed in only 15% of the cases. These results seem to confirm the validity of the strategy (widely used today in the neoadjuvant treatment of non-metastatic osteosarcoma) of changing the postoperative treatment when the histologic response of the primary tumor is poor. At an average follow-up of 3.5 years, only 6 patients remained disease-free; 19 patients relapsed and 1 patient died for adriamycin cardiotoxicity. Of the 19 relapsed patients, 16 died and 3 are still alive but with uncontrolled disease. These results are much worse than those obtained in 144 cases of non-metastatic osteosarcoma of the extremities treated in the same period with the same preoperative chemotherapy (77% with good response in the primary tumor and 78% with continuous disease-free survival). The data suggest that a very effective neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities gives disappointing results in osteosarcoma of the extremities which is metastatic at presentation. PMID- 1440947 TI - Colonic metastasis of a renal carcinoma. A case report. AB - A 64 year-old man with a metastatic clear-cell renal carcinoma experienced low intestinal bleeding. The endoscopy revealed a polypoid mass in the left colon which proved to be a metastasis of the renal carcinoma. This is an uncommon cause of intestinal hemorrhage, and a rare localization of metastatic deposits. PMID- 1440946 TI - Case report: a patient with Hodgkin's disease after treatment for testicular cancer. AB - A young patient developed Hodgkin's disease 11 years after surgical, chemotherapeutic and radiation treatment for stage IIIA embryonal carcinoma of the testis. The importance is stressed of establishing a tissue diagnosis when there is an unexpected course of the disease. PMID- 1440948 TI - The effect of nifedipine on secretory diarrhea in mice. AB - The aim of this study was to determine whether castor oil-induced secretory diarrhea in mice could be ameliorated by nifedipine, a calcium channel blocking agent in mice. Ten animals received nifedipine in a dose of 1 mg/30 g/body weight and another ten animals received only distilled water via an orogastric feeding tube. Fifteen minutes after the administration of the drug or the distilled water, castor oil was given to all animals. The mean body weight loss was found to be higher in the control group than in the nifedipine treated group two hours after the administration of castor oil. These findings indicate that nifedipine may have a therapeutic role in castor oil-induced secretory diarrhea. PMID- 1440949 TI - Neuroblastoma presenting as protein-losing enteropathy. AB - Protein-losing enteropathy is often reported to be associated with malignancies such as Hodgkin's disease, non-Hodgkin's lymphoma, and mesenteric mesenchymoma, but it seldom complicates neuroblastoma. In this report, we describe a case of neuroblastoma presenting as protein-losing enteropathy in which neurohumoral mechanisms were involved. PMID- 1440950 TI - A case of Waardenburg syndrome and aganglionosis. AB - Waardenburg's syndrome is characterized by a broad nasal root, pigmentation disturbance and congenital deafness while aganglionosis is described as the partial or complete lack of ganglion cells in the alimentary tract. This report describes a five-day-old male infant with Waardenburg's syndrome associated with total aganglionosis of the colon, ileum and distal jejunum and draws attention to the causal relationship between these two entities. PMID- 1440951 TI - Kawasaki syndrome. AB - Kawasaki syndrome, also known as mucocutaneous lymph node syndrome, is an acute vasculitis of infants and young children. We describe a four-year-old girl who presented with fever, a diffuse erythematous maculopapular rash, bilateral nonpurulent bulbar conjunctivitis, dry, red, fissured lips, a tongue with a strawberry "appearance", an erythematous pharynx, indurative erythema, and edema and desquamation of the face, hands and feet. She probably developed mitral valve prolapse during the course of the disease. The diagnosis of Kawasaki syndrome was arrived at by excluding other diseases and by the presence of all the clinical criteria for Kawasaki syndrome. Since this syndrome is rarely encountered in Turkey, this case is presented and the literature regarding the syndrome is reviewed. PMID- 1440952 TI - Evaluation of growth hormone secretion and insulin-like growth factor-1 in prepubertal children with thalassemia. AB - Growth retardation is a clinical feature of patients with thalassemia major, and endocrine studies have frequently revealed the presence of normal growth hormone (GH) secretion. The present study was undertaken in 14 prepubertal thalassemic children (9 males and 5 females), aged 2(2/12) to 10(3/12) years, with the aim of evaluating GH response to i.v. arginine, oral L-dopa stimulation and insulin-like growth factor-1 (IGF-1) levels. Eleven patients had peak serum GH levels less than 7 ng/ml and two patients had peak serum GH levels of 7-10 ng/ml with arginine. Similarly, 10 patients had peak levels less than 7 ng/ml and one patient had a peak level of 7-10 ng/ml with L-dopa. Thus, nine of the patients had GH deficiency and two had partial GH deficiency. Three patients had elevated basal GH values. The serum IGF-1 levels in the patients were not statistically different from the levels in the controls, but three patients had low IGF-1 values. These findings suggest a defect in the regulatory mechanisms of GH secretion. PMID- 1440953 TI - The role of viruses and Mycoplasma pneumoniae in lower respiratory tract infections in childhood. AB - Acute lower respiratory tract infections are one of the major causes of childhood morbidity and mortality in developing countries. This study was undertaken at Hacettepe University Children's Hospital to determine the role of viruses and Mycoplasma pneumoniae in respiratory tract infections in children. Eighty-three patients with lower respiratory tract infections were selected at random from among the children admitted to the hospital for evaluation of respiratory symptoms. Acute and convalescent serum samples were collected from all patients for the complement-fixation test and the following antigens were used: respiratory syncytial virus (RSV), adenovirus, parainfluenza virus Type 1, influenza viruses A and B, and Mycoplasma pneumoniae. The test was positive in 39 of 83 patients (47%), and RSV was the most frequent agent detected serologically (15.7%). PMID- 1440954 TI - Carrier detection by DNA analysis in Duchenne muscular dystrophy families. AB - We applied DNA analysis techniques to Turkish families whose members were afflicted with Duchenne/Becker muscular dystrophy. The aim of this study was to establish a prenatal diagnosis of this anomaly and to determine the carrier state. All of the techniques used in established diagnosis centers are now applied routinely in our laboratory. Both Southern analysis and polymerase chain reaction (PCR) methods were used for deletion detection in patients and restriction enzyme fragment length polymorphism (RFLP) determination for linkage analysis in women at risk. CA repeated sequence length polymorphism, the most recent technique for linkage analysis, was also applied. About 250 individuals from seventy-nine families were investigated and thirty-six entire families were screened. Twenty-five women were found to be carriers while thirty seven were non carriers. The carrier state could not be determined in three women. PMID- 1440955 TI - The significance of early panendoscopy in caustic ingestion in children. AB - Fourteen cases of esophageal and gastric burns following the accidental ingestion of a caustic substance are presented. Early fiberoptic endoscopy was necessary, for it made possible a precise assessment of the severity and extent of injury and the application of proper conservative therapy. Signs and symptoms of caustic burns in children are an unreliable guide to injury, therefore, panendoscopy should be performed as soon as possible. A delay in the performance of a fiberoptic examination could result in the perforation of the affected organs. PMID- 1440956 TI - The value of CSF adenosine deaminase levels in the differential diagnosis of childhood meningitis. AB - In this study, adenosine deaminase (ADA) levels of serum and cerebrospinal fluid (CSF) in a total 28 children (13 with bacterial meningitis, 5 with mumps meningoencephalitis and 10 with febrile convulsions) were determined. The comparisons between the serum values were insignificant (p greater than 0.05) but the CSF levels of the children with bacterial meningitis were higher than in the others (p less than 0.05). These findings suggest that serum ADA levels are not important in the diagnosis and differential diagnosis of these diseases. However, ADA levels of CSF may be useful in differentiating between bacterial and viral meningitis. PMID- 1440957 TI - [Use of water-soluble 2-nitro-4-sulfophenyl ester of adipic acid for preparation of peptide protein conjugates]. AB - Two synthetic peptides were conjugated with bovine serum albumin by means of 2 nitro-4-sulfophenyl ester of adipic acid. The amino acid analysis of the conjugates has shown that 14-15 molecules of the peptide are coupled per 1 molecule of the albumin during 10 min. The number of coupled molecules is the same when the reaction time increases to 24 hours. So, 2-nitro-4-sulfophenyl ester of adipic acid may be used parallel with the known bifunctional reagents to obtain peptide-protein conjugates. PMID- 1440958 TI - [Effect of the degree of liposome oxidation on adsorption by montmorillonite]. AB - The influence of the degree of liposomes oxidation on the parameters of their adsorption by montmorillonite was studied. It was shown that accumulation of the products of oxidation in liposomes, which occurred in the process of their incubation, feebly influenced the ability of liposomes to adsorb on the surface of the clay mineral. The increase of the degree of liposomes oxidation in this case lead to the lowering of the values of adsorption heats, however the kinetics of heat production was preserved. PMID- 1440959 TI - [Status of the antioxidant protective system of rat liver exposed to carbon tetrachloride]. AB - The dynamics of enzyme activity of antioxidative protective system of the liver and the content of restored glutathione have been studied in rats poisoned by CCl4 injection. During the first hours followed the injection against the background of maximum accumulation of dienic conjugates and decrease of the restored glutathione level no significant changes in the enzyme activity of the antioxidative protective liver system were observed. At the same time 48 hours later the superoxide dismutase and catalase activity decreased by 38% and 36%, respectively, with relative stability of glutathione-dependent enzymes and a two fold increase of the restored glutathione level. It is shown that a fall of activity of the cytoplasmic antioxidative liver enzymes is not a result of the immediate inactivating effect of free-radical reactions initiated by CCl4, but is, evidently, caused by the covalent binding of its radical metabolites with corresponding macromolecules. PMID- 1440960 TI - [Hydrolysis of polymeric fibrin by plasmin, miniplasmin, microplasmin and trypsin]. AB - 125I-labeled polymeric fibrin hydrolyzed with plasmin, Val442-plasmin (miniplasmin, Lys530-plasmin (microplasmin) and trypsin has been studied for radioactivity of its separate electrophoretic bands. The reaction of hydrolysis was stopped at a moment of a two-fold decrease of the fibrin clot turbidity (t1/2) at the wave length 350 nm. For plasmin, miniplasmin, microplasmin and trypsin taken in the same caseinolytic activities t1/2 was 12.4, 40.0 164.1 and 76.8 min, respectively. Differences in composition of fibrin digests taken at t1/2, are demonstrated: the content of high-molecular components of digests decreases in the order of plasmin greater than miniplasmin greater than microplasmin greater than trypsin, thus showing differences in the processes of fibrin clot structure disruption by the enzymes. PMID- 1440961 TI - [Isolation of steroid-binding proteins on new affinity adsorbents]. AB - Steroid-binding proteins of human blood are extracted and investigated on corticosteroid-hydrazide-oxypropyl-adsorbents by the affinity chromatography. The role of structural changes in the matrix-spacer-ligand system for different types of adsorbents is studied as well as a dependence of sorption on pH and salt environment. A dependence of the protein sorption on the isolated hydrazide groups is revealed. It is shown that hydrocortisone displays the highest binding activity to the protein pool in the affinity electroimmunoassay while the substance S-Reichstein and its 16-alpha-methyl analog--the least one. PMID- 1440962 TI - [Biochemical bases of prevention of the cytotoxic effect of xenobiotics]. AB - Possible sources of cytotoxicity of xenobiotics and main mechanisms of realization of their damaging effect are briefly considered. Protective system of a cell is characterized with regard for the peculiarities essential for development of principles of alimentary prophylaxis of cytotoxic effects of foreign compounds. Modern approaches to alimentary modification of the processes of biotransformation of xenobiotics and promotion of protective capacities of a cell are discussed. PMID- 1440963 TI - [Structure and properties of the cell nucleus chromatin in the brain of rats exposed to gamma-radiation]. AB - Exposure of rats to radiation in a dose of 1 Gy changes sensitivity of chromatin in the cerebral cortex cells to the action of DNAase 1, which promotes an increase of the DNA hydrolysis level and content of dissolved chromatin fractions. A day after irradiation the chromatin structure restores only partially and then (7-30 days after irradiation) it passes into a new, less compact state. The irradiation changes the chromatin ability to aggregation in the presence of Mg2+ and spermidine. PMID- 1440964 TI - [Changes in the intensity of DNA synthesis in immunocompetent mouse tissues by peptidoglycans of bacterial origin]. AB - The data are presented on the effect of activation of by peptidoglycans from cell walls of Staphylococcus aureus and Brevibacterium flavum on the DNA synthesis intensity in the mice spleen, thymus and bone marrow in vivo. Maximum of the peptidoglycan influence on the DNA synthesis intensity is observed 12-36 hours after injection. As a rule, higher doses of the studied peptidoglycans (1 mg per one animal) activate the DNA synthesis more efficiently. Peptidoglycan from Br. flavum stimulates the DNA synthesis in all tissues more intensively then the peptidoglycan from S. aureus, which may be a result of its monomers' structure. PMID- 1440965 TI - [Coenzyme-binding sites of the brain pyruvate dehydrogenase complex]. AB - It is shown that the relative amount of the holoenzyme in the highly purified pyruvate dehydrogenase complex from the bovine brain is higher when the enzyme activity is assayed in the reaction of nonoxidative formation of acetaldehyde as compared to the pyruvate: NAD+ reductase reaction. The S0.5 values for thiamine pyrophosphate are as following: (TPP) (0.314 +/- 0.22) x 10(-7) M with reaction of nonoxidative formation of acetaldehyde, (0.188 +/- 0.08) x 10(-6) M and (1.65 +/- 1.16) x 10(-6) M in case of the pyruvate: NAD+ reductase reaction. TPP in the concentration of (0.5-6.0) x 10(-7) M completely protects the sites of nonoxidative formation of acetaldehyde from modification by the coenzyme analogs, 4'-oxythiamine pyrophosphate and tetrahydrothiamine pyrophosphate. However, the pyruvate: NAD+ reductase activity of the pyruvate dehydrogenase complex is inhibited in this case by 30-34%. The data obtained suggest that in contrast to the pyruvate: NAD+ reductase reaction the conversion of pyruvate to acetaldehyde occurs by the sites which tightly bound TPP. PMID- 1440966 TI - [Inhibition of yeast pyruvate decarboxylase by alkyl phosphates]. AB - It is found that yeast pyruvate decarboxylase is inhibited by alkyl phosphates. Inhibition is competitive with respect to a substrate. The inhibition constants with n-butyl and n-heptyl esters of phosphoric acid are the values of the same order of magnitude. With an increase in the length of the alkyl phosphates hydrocarbon chain from 7 to 10 carbon atoms inhibition constants change drastically. For n-heptyl phosphate and n-decyl phosphate values KI are equal to 1.6 x 10(-4) M and 1.7 x 10(-6) M, respectively. A further increase in the number of carbon atoms in the alkyl substituent of phosphoric acid ester induces no reduction of the inhibition constant. Multiple-inhibitor experiments of pyruvate decarboxylase show that inorganic phosphate and n-decyl ester of phosphoric acid are mutually exclusive. It is suggested that the inhibition mechanism with alkyl phosphates includes the competition of the phosphoric acid residue with alpha ketocarboxyl group of pyruvate as well as the interaction between a hydrocarbon radical and hydrophobic parts on the enzyme surface, one of them being outside the substrate binding site. PMID- 1440967 TI - [Activity of glutathione-dependent enzymes and superoxide dismutase in peptic ulcer]. AB - Activity of Cu, Zn-superoxide dismutase, glutathione-S-peroxidase, glutathione-S transferase, glutathione reductase, glucoso-6-phosphate dehydrogenase and content of glutathione reduced in blood of patients with gastric and duodenal ulcer depending on the age and parallel lesion of the hepatobiliary system have been studied. Considerable inhibition of superoxide dismutase, glucoso-6-phosphate dehydrogenase activity and decrease of the content of reduced glutathione, the most pronounced in patients with parallel lesion of the hepatobiliary system, have been revealed. Glutathione reductase activity is high in all the patients, except for aged and old people with parallel lesions of the liver and biliferous tracts. Glutathione peroxidase is essentially active in adult patients, especially in case of combined pathology. Glutathione peroxidase activity is lower in aged and old patients as compared to the age norm, while the level of glutathione-S-transferase activity is high; at the same time there are no considerable changes in the glutathione-S-transferase activity in adult patients. The mechanisms of compensation and decompensation of functioning of enzymatic antiradical and antioxidant system under the peptic ulcer depending on the age of patients and concomitant lesions of the hepatobiliary system are discussed. PMID- 1440968 TI - [Redox processes in the retina and tunic tissues of the rat eye in experimental alkalosis]. AB - It is shown in experiments is vivo that development of experimental metabolic alkalosis in rats is followed by changes in redox processes in the eye retina and tunic. For the first two months of the experiment the number of sulphydryl group decreases, while that of disulphide ones of water-soluble proteins and low molecular compounds increases. The amount of oxidized metabolites of glycolysis and of a cycle of tricarboxylic acids (pyruvate, oxaloacetate, alpha ketoglutarate) increases relative to the reduced ones (lactate, isocitrate, malate), as well as activities of hexokinase, pyruvate kinase, NAD-dependent malate dehydrogenase, while activities of fructose diphosphatase, glucoso-6 phosphate dehydrogenase, glutathione peroxidase and glutathione reductase fall. The content of malonic dialdehyde increases. 90 days later disorders of certain compensatory mechanisms of the metabolic system of alkalosis regulation probably occurred in the eye retina and tunic tissues: hexokinase and pyruvate kinase activity fell to the control values, while that of NAD-dependent malate dehydrogenase--below the control level; the content of lactate increased. Activity of glutathione-dependent enzymes remained low and the amount of malonic dialdehyde grew much more than in the previous terms. PMID- 1440969 TI - [Ammonia metabolism in tissue of newborn animals in health and in digestive disorders]. AB - Ammonium nitrogen was studied for its metabolism in the tissues of ruminants in transition from pre- to postnatal development in norm and with disorders in gastroenteric digestion. It is established that the intensity of ammonium genesis and glycolysis processes as well as a cycle of tricarbonic acids change in newborn calves as compared to adult animals. The ammonium toxicosis development in sick animals, which is confirmed by an increase of the ammonia level and intensification of the reactions of ammonium- and ureogenesis in tissues of the gastroenteric tract, liver and kidneys. PMID- 1440970 TI - [Effect of ketoconazole on the activity of key enzymes of biosynthesis of cholesterol and its esters in the liver of rats maintained on a cholesterol enriched diet]. AB - Ketoconazole in vivo has been studied for its effect on the activity of key enzymes of the cholesterol and its esters' biosynthesis in the liver and on the cholesterol concentration in certain fractions of blood lipoproteins in normal and cholesterol-fed rats. It is established that ketoconazole decreases cholesterol concentration in low-density lipoproteins and in very low-density lipoproteins as well as decrease the acyl-CoA-cholesterol acyl-transferase activity and increases the 3-hydroxy-3-methyl-glutaryl-CoA-reductase activity in the liver microsomes of intact and test animals. It is supposed that the possible cause of the observed changes can be a disturbance in regulation of basic links of cholesterol metabolism in the liver. PMID- 1440971 TI - Alkyllysophospholipid influenced melanoma cell morphology is associated with decreased attachment to basement membrane. AB - The alkyllysophospholipid analog 1-0-octadecyl-2-0-methyl-3-phosphorylcholine (ET 18-OCH3) was examined for possible anti attachment effects on B16-F10 murine melanoma cells in vitro. At sub-lethal lipid concentrations B16-F10 cells were inhibited from attaching to reconstituted basement membrane (Matrigel) during a 45 min assay. This type of inhibition was also imparted by the isoprenoid farnesol but not by egg lysophosphatidylcholine (LPC) at concentrations up to 10 micrograms/ml. Both lipids were toxic to B16-F10 cells in the absence of bovine serum albumin (BSA), BSA (0.1%) completely protected the cells from lysis except when both lipids were combined as a mixture. Light and electron microscopy, as well as electronic sizing of cells, gave evidence of alkyllysophospholipid induced reduction in cell size which correlated well with attachment inhibition. The results suggest that alkyllysophospholipid induced reduction of cell surface area leads to inhibition of cell attachment to basement membrane which 8 with our experimental conditions, was not permanent since cells eventually attach within 24 h after treatment. The enhanced lytic effect the lysophospholipid imparts on the alkyl compound, in conjunction with the anti-attachment properties should be important areas for future research. PMID- 1440972 TI - [Effect of salvipholin on the carbohydrate and lipid metabolism in the rat liver in alloxan diabetes]. AB - Peroral administration of salvipholin in a dose of 50 mg/kg to intact male rats (the body weight 180-220 g) had a positive effect on the carbohydrate-lipid metabolism in the liver and blood serum of animals. Administration of the same dose to rats with alloxan diabetes induced a significant decrease in the content of glucose, free fat acids, triglycerides and lysophospholipids of the liver and blood serum. The level of these components has sharply increased after subcutaneous alloxan administration in a dose of 150 mg/kg, the content of glycogen and pyruvic acid being normalized and insulin deficiency removed. These changes are closely related to salvipholin-promoted restoration of phospholipid spectra of the blood serum and liver of experimental animals disturbed under conditions of insulin deficiency. The possible mechanism of the salvipholin action is analyzed. PMID- 1440973 TI - [Blood lipids and characteristics of free radical processes in specific classes of lipoproteins in rats in the early periods after gamma-radiation]. AB - The content of lipids and lipoproteins, the state of free-radical processes and the level of eicosanoids (prostaglandin F-1L and thromboxane B-2) have been studied in the blood plasma and in certain classes of lipoproteins in rats 2 and 24 h after external gamma-radiation in doses of 1.2 and 3 Gy. Hypertriglyceridemia and hyperprebetalipoproteinemia, whose expressivity increases with a radiation dose are revealed. The activation of free-radical processes, an increase of the thromboxane V-2 content and a decrease of the prostaglandin F-1L content are observed with a dose of 1 Gy. PMID- 1440974 TI - [Cellular microbiosensors for methanol and ethanol determination on the basis of pH-sensitive field transistors]. AB - Cellular sensors for methanol and ethanol determination were developed using immobilized mutant cells of methylotrophic yeasts Hansenula polymorpha and Pichia pinus (able to extrude protons in the presence of alcohol) and pH-sensitive field effect transistors (pH-SFETs). The intact cells of yeasts were immobilized in Ca alginate gel to obtain a biomembrane. The minimal detectable response was obtained to approximately 0.5 mM of methanol and ethanol, a linear dependence of biosensor's response on the logarithmic alcohol concentration was observed in the range from 5 to 100 mM for both types of alcohol. The prospects for application of biosensors to determine alcohols in the analytical practice are discussed. PMID- 1440975 TI - Comparative ultrastructure of needle aspiration biopsy and surgical resection specimens of lung tumors. AB - Ultrastructural examination affords conclusive evidence for classification of lung tumors. Tissue properly fixed for electron microscopy is not available in many cases, however. Ultrastructural diagnosis of resected specimens obviously follows, rather than directs, the surgical treatment. Fine-needle aspiration (FNA) of lung masses is recommended as a means to obtain lung tumor tissue for electron microscopy. Nevertheless, no comparison has been made between ultrastructural information gained from aspiration specimens and resected specimens. Electron microscopy was performed on transthoracic FNA specimens of 10 lung tumors for which surgical resection was subsequently performed. Glutaraldehyde-fixed specimens from FNA and surgical resection were prepared for electron microscopy according to routine procedures. Fixation of the FNA specimens was equivalent or superior to that of the resected specimens in 9 of the cases. Three of the FNA specimens contained necrotic as well as viable tissue. Features essential for diagnosis such as desmosomes, junctions, neurosecretory granules, intermediate filaments, glycogen, lipid, mucin, and microvilli were identifiable in both FNA and resected specimens. FNA specimens therefore yield a representative sample of the ultrastructural features of lung tumors when adequate cellular material is obtained. Use of a coaxial needle sampling technique with immediate microscopic assessment reduces the likelihood of retrieving only blood or necrotic tissue in the electron microscopy specimens. PMID- 1440976 TI - Acute myopathy associated with chronic licorice ingestion: reversible loss of myoadenylate deaminase activity. AB - A patient with acute rhabdomyolysis and absence of myoadenylate deaminase (MADA) associated with chronic licorice intoxication is presented. Clinical and laboratory examination of the patient and morphologic study over skeletal muscle were performed. The major effect of licorice intoxication is hypokalemia, which may explain most of the observed clinical symptoms and morphological changes. The absence of MADA may be a consequence of the direct toxic effect of licorice glycosides. To our knowledge, this is the first report in which a lack of MADA and chronic licorice intoxication has been shown to be associated with clinical, histochemical, biochemical, and morphological changes, which were completely reversed with potassium supplementation and licorice withdrawal. PMID- 1440977 TI - Ciliary ultrastructure in primary ciliary dyskinesia and other chronic respiratory conditions: the relevance of microtubular abnormalities. AB - Twenty-eight subjects with chronic respiratory disease were investigated for clinical data, ciliary beat frequency of nasal mucosa (10 cases), and ciliary ultrastructure. The cases were divided into two groups: those considered compatible with primary ciliary dyskinesia (genetic), and those not fitting into this category (others). A case was defined as genetic if one or more of the following were present: dextrocardia, ciliary beat frequency less than 10 Hz, or an average dynein arm count (outer, inner, or both) of less than two per ciliary cross-section. In each of the genetic cases at least two of these parameters were present. The percentage of malformed microtubules was calculated from the total number of evaluated cross-sections for each case. Ciliary microtubular abnormalities of any kind were no more frequent in cases of primary ciliary dyskinesia than in other cases. The same was true for transposition and radial spoke defects. PMID- 1440978 TI - Chordomalike soft tissue sarcoma in the leg: a light and electron microscopic and immunohistochemical study. AB - A soft tissue tumor in the leg of a 67-year-old woman is described. This large tumor below the knee area infiltrated extensively the deep and superficial soft tissues but did not involve the bones. The tumor cells formed nodules resembling the architecture seen in chondroid tumors and chordoma. The tumor cells were often vacuolized, and there was extracellular myxoid matrix similar to that in chordoma or myxoid chondrosarcoma. Immunohistochemistry showed keratins 8 and 19, epithelial membrane antigen, and vimentin in most tumor cells, and there was also S-100 protein positivity in a number of tumor cells. Electron microscopy showed desmosomelike cell junctions and bundles of intermediate filaments resembling those seen in many epithelial neoplasms. Thus the tumor resembled chordoma in many respects. Because clinically no other primary tumor was found, this tumor is probably a chordomalike primary soft tissue sarcoma different from typical extraskeletal myxoid chondrosarcoma or chordoid sarcoma. PMID- 1440979 TI - Metastatic spindle cell malignant melanoma with prominent microvilli. AB - A metastatic spindle cell malignant melanoma with positive immunoreactivity for S 100 protein and HMB-45 antigen and the presence of premelanosomes is described in a lymph node of the neck 11 years after removal of a superficial spreading malignant melanoma from the arm. Ultrastructurally, long, slender microvilli created a pattern with great similarity to an anemone cell tumor. A more solid pattern without microvilli was also present. Despite the abundance of microvilli in the anemone part of the tumor, intracytoplasmic lumina were not observed. In addition, crystalline structures within enlarged mitochondria and intracisternal tubules were noted. PMID- 1440980 TI - Osteoclastic origin of giant cells in giant cell tumors of bone: ultrastructure and cytochemical study of six cases (UP 15:623-629) PMID- 1440981 TI - Limits of cryofixation as seen by Fourier transform infrared spectra of metmyoglobin azide and carbonyl hemoglobin in vitrified and freeze-concentrated aqueous solution. AB - The limits of cryofixation were probed by investigating metmyoglobin azide and carbonyl hemoglobin in approximately 5 wt% aqueous solution by Fourier transform infrared spectroscopy. Spectra of solutions cooled slowly and recorded in steps between 295 K and 190 K are compared with those obtained by "hyperquenching" either into their glassy states at 80 K, or into freeze-concentrated solution at 170 K. For metmyoglobin azide we conclude from an analysis of its covalently and ionically bound azide that it is impossible to freeze-in its high-spin/low-spin equilibrium even by hyperquenching, and that its vitrified state must correspond to a temperature T < 226 K for the Fe(II) site of the protein. In the amide I spectral region of carbonyl hemoglobin (HbCO), a band at approximately 1654 cm-1 due to alpha-helical structures is the dominant band in spectra recorded at ambient temperature and in the vitrified state, but in the spectrum of HbCO quenched at similar rates into a freeze-concentrated state, a band at approximately 1650 cm-1, tentatively assigned to unordered structures, becomes the dominant feature. This band is absent in the spectra of freeze-concentrated samples obtained by heating a vitrified sample to 170 K. We surmise that HbCO is dehydrated by freeze-concentration to a larger extent in solution quenched rapidly at 170 K than in a vitrified solution heated to 170 K, and that this dehydration is the primary cause for HbCO's perturbation. We conclude that freeze concentration induced by heating a vitrified solution can cause less perturbations of a protein than does quenching into a freeze-concentrated state. Therefore it can be advantageous for the practice of freeze-etching to vitrify first a solution by "hyperquenching" and thereafter freeze-etch at e.g. approximately 170 K. PMID- 1440983 TI - New STEM multisignal imaging modes, made accessible through the evaluation of detection efficiencies. AB - With its specific design for recording simultaneous signals, the scanning transmission electron microscope (STEM) offers unique imaging capabilities. In order to use them fruitfully, we have implemented, on a VG STEM equipped with a magnetic spectrometer, home-made detectors for recording multisignal images. This paper first describes a method developed for the quantitative evaluation of detection efficiency of all data-acquisition channels involved in these multisignal images. At this stage, new imaging modes become accessible, which can be classified following their specificity and sensitivity; scattering power image, elastic and inelastic images mean free path ratio images. Original applications encountered in the biological as well as in the materials science fields illustrate the possibilities of these various approaches, which can be of great interest in quantitative microscopy, analytical imaging or low-dose observation. PMID- 1440982 TI - Scanning tunneling microscopy of an ionic crystal: ferritin core. AB - Ferritin molecules were imaged directly in air by scanning tunneling microscopy (STM). The lateral dimensions were close to the values determined by electron microscopy, and the vertical dimension was much reduced. Several clusters of partially naked ferritin cores displayed a hexagonal structure of lattice constant 4.9 +/- 0.5 A. It is thus shown that the STM can be used to image thin ionic crystals at high resolution. PMID- 1440984 TI - A method for observing cross-sectional views of biomembranes. AB - Cross-sectional views of intact biomembranes and synthetic lipid bilayer membranes were observed by electron cryomicroscopy using spontaneous orientation of disk-shaped membranes; purple membrane, thylakoid membrane, synthetic phospholipid membrane and a microcrystalline sheet made of Er-binding polypeptide were observed. The membranes were observed fully hydrated, embedded in vitreous ice, and their self-orientation was most probably caused by repulsion between their hydrophobic edges and their hydrophilic environment which forced their edges to be exposed to the air-water interface. The cross-sectional profiles of the native biomembranes were asymmetric and characteristic, whilst those of the synthetic membranes were symmetric and predictable by a simple model. Simple Fourier analysis showed that the cross-sectional images retained structural information up to a medium resolution. PMID- 1440985 TI - Ultrasonic analysis of edible fats and oils. AB - Low intensity ultrasound is a powerful analytical technique for investigating the physico-chemical properties of many biological and non-biological materials. In this article its application for the characterization of edible fats and oils is assessed. Ultrasound can be used to determine the dynamic rheology and composition of oils, the oil content and droplet size of emulsions and the solid fat content of partially crystalline emulsions. It is capable of rapid and precise measurements, is non-destructive and non-invasive, can be used on-line or off-line and is relatively inexpensive. Ultrasonic techniques will therefore prove a useful addition to the existing analytical techniques used to characterize fats and oils. PMID- 1440986 TI - The effect of bone structure on ultrasonic attenuation and velocity. AB - The relationship between the structure of bovine cancellous bone, and its ultrasonic propagation parameters is investigated by means of a novel technique involving the application of large static loads, thereby changing the porosity in a controlled manner. The results show that for frequencies in the range 0.4 to 1 MHz, porosity decreases up to 35% are associated with a reduction in attenuation of up to 500%, whereas the velocity increases by roughly 35% for the same changes. The data taken overall suggest that in determining the ultrasonic attenuation coefficient at these frequencies, the amount of material in a given bone section is significantly less important than the distribution of that material. PMID- 1440987 TI - Dependence of ultrasonic attenuation of liver on pathologic fat and fibrosis: examination with experimental fatty liver and liver fibrosis models. AB - To clarify the effect of the pathological state of the liver on ultrasonic attenuation, we produced two experimental rabbit models. The influence of fat on ultrasonic attenuation was examined using a fatty liver model without liver fibrosis, and that of fibrosis on attenuation using a liver fibrosis model without fatty infiltration. Ultrasonic data were obtained in vivo directly from the liver, and an acoustic attenuation coefficient slope was obtained by the spectral difference method. Tissue components of the liver, namely the total lipid, hydroxyproline and water contents, were measured precisely by quantitative methods. We revealed that ultrasonic attenuation depends mainly on fatty infiltration of the liver and to a lesser extent on fibrosis, but not on the water content. PMID- 1440988 TI - Axial stress distributions between coaxial compressors in elastography: an analytical model. AB - We describe an analytical model to study the behavior of stress along the compression axis for different configurations of opposing circular compressors, as applied to elastography. The method is based on a hypothesis that the axial stress at any point on the axis is the superposition of the individual components of the stresses derived from the boundary conditions at either end. The determination of the axial stress behavior according to the model permits the correction of certain elastograms for depth-dependent stress. Experimental results have been presented to corroborate the model. PMID- 1440989 TI - Fetal exposure from endovaginal ultrasound examinations in the first trimester. AB - Ultrasonic obstetrical examinations during the first trimester are now often performed endovaginally with higher-frequency (5-7.5 MHz) transducers operating closer to the fetus than for transabdominal examinations. To estimate exposure to the fetus, propagation distances were obtained from a retrospective study of 100 normal first-trimester endovaginal B-mode examinations. No significant dependence of attenuation on gestational age was observed. The range of the attenuation estimates was 1.8-10.4 dB. A mean attenuation of 5.0 dB at 5 MHz for an average depth of 2.8 cm resulted in an attenuation coefficient of .36 dB/cm/MHz. Exposure (ISPTA) to the fetus at each gestational week from three ultrasound units was very similar: worst-case values of the 100 cases ranged from 1.2-1.9 mW/cm2, well within the Food and Drug Administration (FDA) guidelines of 94 mW/cm2 for derated focused transducers. Energy density deposited to the anterior surface of the fetus during a typical examination, assuming that the transducer is kept stationary over one area for the entire period of the examination (which is unlikely), ranged from 143-217 mJoules/cm2, within the American Institute of Ultrasound in Medicine (AIUM) recommendations. PMID- 1440990 TI - Human in situ dosimetry: differential insertion loss during passage through abdominal wall and myometrium. AB - We constructed a specialized in vivo exposimetry system and determined selected ultrasonic field quantities. We examined two groups of non-pregnant women (nulliparas = 14, multiparas = 9) under conditions of full and empty bladder. A calibrated 7-element linear array hydrophone was placed in the anterior fornix of the vagina in each subject. In the full bladder condition, the sound beam traversed the anterior abdominal wall and full bladder, whereas after voiding, the sound beam traversed the abdominal wall and anteverted uterine fundus. Each study was conducted using a 3.5 MHz mechanical sector transducer. Calibration data were recorded after completion of each in vivo experiment. Data from both groups were pooled for analysis. Assuming (1) the sound path through the full bladder is loss less, the insertion loss (ILFULL) should represent the insertion loss for the abdominal wall (ILABD WALL) 8.2 +/- 5.6 dB; whereas (2) for the empty bladder condition, (ILEMPTY) represents (ILABD WALL+ILUTERUS). Subtracting ILFULL from ILEMPTY yields ILUTERUS = 5.8 +/- 6.8 dB. Therefore, knowing the respective path lengths and normalizing for frequency, the mean tissue attenuation coefficients (A) are estimated to be AABD WALL = 1.39 dB/cm-MHz and AUTERUS = 0.14 dB/cm-MHz. These attenuation data suggest that the abdominal wall is the principal source of ultrasonic energy loss. PMID- 1440991 TI - Apparent contribution of respiratory gas exchange to the in vitro "cell density effect" in ultrasonic cell lysis. AB - Ultrasonic damage to cells in vitro has been reported to vary dramatically with cell density; the particle density per se has been proposed to be responsible for this effect via interference with gas body activity. Reported here are the results of experiments designed to test the general postulate that the "cell density effect" can be explained in part by cellular modification of the suspension medium by respiratory gas exchange. Ultrasonic cell lysis is shown to occur at a much higher level in suspensions supplemented with the respiratory inhibitor NaCN than in control suspensions when suspension densities exceed 2 x 10(7) cells/mL. Moreover, at constant cell density, cell lysis diminishes with increasing pre-insonation incubation time at 37 degrees C. The rate of change in cell lysis with incubation time was diminished significantly by cyanide treatment. These observations are consistent with the postulate that respiratory O2:CO2 exchange enriches the medium in CO2 while depleting the medium of oxygen, which cavitates more readily than CO2, thereby diminishing the potential for cavitation-related cellular damage. However, this is only a partial explanation of the cell concentration dependence of cell lysis; cell density per se is an important factor in the "cell density effect." PMID- 1440992 TI - Ultrasound-enhanced effects of adriamycin against murine tumors. AB - Earlier studies from our and other laboratories have demonstrated that ultrasound (US) enhances the cytotoxicity in vitro of the antitumor agent Adriamycin (Adr) (Harrison et al. 1991; Loverock et al. 1990; Saad and Hahn 1987, 1989; Yang et al. 1991; Yumita et al. 1987, 1989). We have now tested the possibility that this additional cytotoxicity can be translated into antitumor activity in vivo. Mice, bearing either a fibrosarcoma (RIF-1) or a melanoma (B-16) on their thighs, were injected with a single dose of Adr (10-20 mg/kg). The tumors were then heated locally to 41 degrees -43 degrees C for 30 min, either by insonation with US or by immersion of the animals' limbs into hot water baths. Antitumor efficacy was scored two ways: by serial measurements of tumor volume to determine the time for the tumor to double in size, or by determining the X-ray dose required to sterilize 50% of the tumors (TCD50) after the Adr-hyperthermia treatment. Both assays gave similar results. Ultrasound-induced hyperthermia was substantially more effective in enhancing Adr activity than was hyperthermia induced by the water bath. The mean-doubling time was 13 days for tumors treated with the combination of Adr and US and 6 days for tumors heated with a water bath immediately after injection of Adr. The TCD50 was 21.2 +/- 0.8 Gy for the combination of US and Adr and 36.1 +/- 0.9 Gy for the water bath heating and Adr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1440993 TI - The sensitivity of Drosophila larvae to continuous-wave ultrasound. AB - The threshold for killing of freshly hatched Drosophila larvae exposed to continuous-wave (CW) ultrasound shows a minimum at approximately 0.3 MHz. This suggests that the stiffness of the material surrounding the gas bodies in the organism is comparable to water. From this, it is apparent that the gas bodies in three-day-old larvae that we have used in earlier studies are far larger than resonance size at the frequencies (1-5 MHz) used. Yet, these larvae were killed by short exposures to low-temporal-average-intensity pulsed ultrasound with peak intensities of the order of 10 W/cm2. Hence, it appears that "large" bubbles cannot be ignored in considerations of the biological effects of pulsed ultrasound and lithotripsy. PMID- 1440994 TI - [Reparative processes of experimental Aitken III lesion. An animal experiment study]. AB - This present study describes the fine structural aspects of experimentally induced defects of the proximal growth plate of the tibia in rabbits as simulation of epi-/methaphyseal fractures. We evaluated two different defect sizes. As important result we find in narrow defects of 0.5 mm no osseous bridging of the epiphyseal plate whereas with 2 mm defects there is partial transphyseal closure. Growth plate cartilage is thus capable of repairing spontaneously smaller defects. PMID- 1440995 TI - [Ablation of hard biological tissue with the excimer laser]. AB - Cutting and drilling of bone- and meniscus tissue were performed using a XeCl excimer laser combined with a tapered fiber. Ablation speed on meniscus tissue is already sufficient, the thermal damage of the adjacent tissue is minimal. Increasing of energy transmission through special fibers promises higher ablation rates also on hard biological tissue and that promoted the interest in lasers again for accident surgeons. PMID- 1440996 TI - [Effect of form elasticity of the prosthesis shaft in response to stress of the proximal femur]. AB - Uncemented hip prostheses are characterized by a variable design of the stem. In these investigations, nine different prostheses were studied according to the model of a standard bone (Kunststoffnormfemur). After preparation of the cavity of the prostheses with original instruments and after its implantation, strain gauges were placed at 16 certain points. Measurements were carried out in steps of 200 N until reaching the maximal force of 2kN. Prostheses that are characterized by an anatomical design of the stem resemble the physiological nature of normal bone, in contrast to the models with a rectangular cross-section or with a stretched lateral shape of the stem. PMID- 1440997 TI - [Thoracopulmonary complications of fresh fractures of the thoracic spine with neurologic damage]. AB - The number of thoracic injuries associated to traumatic fractures of the spine is increasing. The multiple trauma rate in this retrospective study of 253 spinal injuries with neurological damage, which needed admission to the Intensive Care Unit, was of 55%. Blunt chest trauma was found in 86% of the multiple trauma group, especially in combination with fractures of the upper and middle thoracic spine (up to 100%), while head injuries appeared in only 58%. Hemopneumothorax was diagnosed in 88%, pulmonary contusion in 48% of the cases, leading to a high rate of recidivating atelectasis and pneumonia. Emergent chest computed tomography should therefore be obligatory in thoracic spine fractures. PMID- 1440998 TI - [Possibilities for avoiding homologous blood transfusion in surgical interventions]. AB - Alternative techniques to reduce the need for homologous blood transfusions are clinically available for several years. Actually a decision of our federal constitutional court (Bundesgerichtshof) outlined the medicolegal importance of autologous blood transfusion concepts. Pre-operative donation of red cells and/or plasma, acute normovolemic hemodilution, and intraoperative blood salvage and retransfusion will be discussed in terms of effectiveness, advantages, indications, and contraindications. In an emergency hemorrhage situation only the intraoperative blood salvage and retransfusion is available. The other autologous concepts are important in elective surgery. PMID- 1440999 TI - [Experiences with the isoelastic prosthesis in treatment of humerus metastases]. AB - 39 patients with pathological fractures of the humerus were treated by isoelastic polyacetal endoprosthesis. Ten patients received a humeral-head-prosthesis and 32 a prosthesis of the humeral-shaft. The average survival time was nine months. Three times within the first group of twelve patients fracture of the cone of the prosthesis occurred. Therefore an additional stabilization of the contact zone between bone and prosthesis by plate-osteosynthesis was performed in the following 20 operations, preventing breakage of the material. In contrast to the conventional posterior approach to the humeral-shaft we chose a ventrolateral approach between the biceps and triceps muscle. This technique is less traumatic and leads to a shorter operation time. In patients with pathological humeral fractures a conception of treatment is demonstrated which provides an immediate stability by using endoprostheses to preserve the quality of life of oncological patients. PMID- 1441000 TI - [Combined injury of the anterior cruciate ligament and the medial collateral ligament of the knee joint--results of two to six years follow-up of surgical treatment]. AB - A retrospective study of 148 combined acute knee injuries with anterior cruciate and medial collateral ligament injuries was performed. Follow-up included 115 patients, 95 of whom were personally examined two to six years postoperatively. Proximal anterior cruciate ligament ruptures were treated with reinsertion in 96 patients, in case of intraligamentous lesions (44 times), augmentation with the semitendinosus tendon was performed. Medial collateral ligament lesions were explored during the operation. Reconstruction of intraligamentous ruptures was performed with sutures (120 times). Distal lesions were refixed with Burri plate or staple. A modified Ellison procedure was routinely performed. Postoperative treatment was cast-free and included immediate physiotherapy using a functional brace. Between the two groups with anterior cruciate ligament reinsertion and augmentation, no significant differences were observed in subjective evaluation (Lysholm score 85 vs. 88), activity level (Tegner score 5.5 vs. 5.4) or anterior stability (KT 1000 at 89 N 6.6 vs. 6.1 mm displacement). A clear pivot shift sign was noted in two knees with reinsertion and in none of the augmented group. Medial stability was reestablished almost completely, independent of the site of lesion or the reconstruction technique (average valgus movement at 30 degrees flexion 0.7+ vs. 0.5+ on injured/contralateral side). We conclude that reinsertion of femoral anterior cruciate ligament ruptures will reestablish anterior stability in most cases, although semitendinosus augmentation appears to give slightly more reliable results. Medial stability is gained by the site depending reconstruction techniques. Whether intraligamentous medial collateral ligament lesions can be left alone with only the anterior cruciate ligament being reconstructed, cannot be answered by this study. PMID- 1441001 TI - [Immobilization and early mobilization of malleolar fractures after osteosynthesis with resorbable bone screws]. AB - 71 patients with displaced ankle fracture were treated by using absorbable screws in the fixation of fractures. The follow-up time was 17 (13 to 33) months in average. The fixation devices were SR-PLLA (self-reinforced poly-L-lactide) and SR-PGA (self-reinforced polyglycolide) screws. 38 of the ankle fractures were immobilized with plaster cast and 33 ankle joints were mobilized immediately with a brace. An exact radiological result was achieved in 66 cases, insignificant displacement was observed in four cases and the result was poor in one patient. The result was classified as excellent in 62 patients, as good in eight patients and as poor in one patient. The patients treated postoperatively without plaster healed in a somewhat shorter time, but at one year check-up the differences in the clinical results were almost eliminated. Selected ankle fractures fixed with absorbable screws can be treated postoperatively with early mobilization without plaster. PMID- 1441002 TI - [Traumatic hematoma of the adrenal gland simulating pheochromocytoma. A case report]. AB - A young man with Weber B fracture had adrenalectomy under the suspicion of pheochromocytoma on the right side. Surprisingly hematoma of the right adrenal gland was found. This case is presented to point out the mechanism of trauma and diagnostic possibilities of the injury. PMID- 1441003 TI - [Textually transmitted diseases]. PMID- 1441004 TI - [Pneumococcal vaccine: a solution in clinical studies?]. PMID- 1441005 TI - [Sinusitis: the maxillary sinus should not necessarily be the focus of treatment]. PMID- 1441006 TI - [Declaration on influenza vaccination for the 1992-1993 season. National Consultative Committee on Immunization (NCCI)]. PMID- 1441007 TI - [Periodical physical examination. 1991 update. 4. Screening for cystic fibrosis of pancreas (mucoviscidosis). A Canadian study group on periodical physical examination]. PMID- 1441008 TI - [Percutaneous transluminal angioplasty of peripheral arteries: past, present and future]. AB - Balloon percutaneous transluminal angioplasty (PTA) has been described in 1974 and has since been considerably refined with the improvement of balloon catheters, guide wires and radiology equipment. Laser and other mechanical recanalization devices have not hold to their initial promises. Clinical and angiographic indications for PTA have been better defined over the years, resulting in excellent clinical successes with low morbidity and very low mortality. PTA has become an almost painless procedure and may be done on an outpatient basis. It is considered as the treatment of first choice in suitable patients. PMID- 1441009 TI - Microwave coagulation therapy on VX-2 carcinoma implanted in rabbit urinary bladders. AB - In order to evaluate the effectiveness of microwave coagulation therapy on urinary bladder carcinoma, we conducted a series of experiments using carcinoma VX-2 cells designed for the application on animal hosts. Three days after implantation of VX-2 cells into the bladder of the rabbits, microwave coagulation therapy was performed. The antitumor effect, i.e. the survival rate, the histological study and the immunological response of the microwave therapy was examined in comparison with the control group (no treatment), the partially cystectomized group and the sham-operated group (no tumor cell implantation). The results were obtained as follows. (1) The survival rate in the microwave group was greater than that in the control group. (2) The stimulation index value (SI), which represents humoral immunity, decreased postoperatively in all groups. In the microwave group, SI increased gradually beginning 21 days after the transient decrease. (3) Histological findings revealed severe degeneration, necrosis and complete eradication of the cancer cells of the bladder wall in the microwave group, however, perforation of the urinary bladder could not be detected. The results indicate that microwave coagulation therapy is an effective procedure for urinary bladder tumors. Furthermore, microwave therapy may also accelerate the inactivation of immunological suppressors in the carcinoma host, an additional benefit of the microwave procedure. PMID- 1441010 TI - Evaluation of seminal vesicle characteristics by ultrasonography before and after ejaculation. AB - Twenty males underwent transrectal ultrasonography before and after ejaculation to examine possible alterations that could influence interpretation of seminal vesicle ultrasonography. The preejaculation length of 35 mm was significantly (p < 0.05) decreased to 30 mm after ejaculation. The mean width of the seminal vesicles was 13 mm before and 11 mm after ejaculation. The seminal vesicle volume was significantly diminished after ejaculation (p < 0.05). It therefore seems important to maintain a period of abstinence when evaluating the seminal vesicles by ultrasonography. PMID- 1441011 TI - Lithiasis in the ileal conduit and the continent urinary pouch: two cases and a review. AB - We present 2 patients who developed stones (6 and 57 g) in the ileal conduit; the first stone was passed and the second required surgical removal; its nidus was a surgical staple. After a review of the literature which includes 25 other cases of stones in ileal conduits, as well as over 20 cases of stones in continent urinary pouches, it is concluded that the use of metallic staples in the construction of the ileal conduit or the continent urinary pouch should be abandoned. PMID- 1441012 TI - The forgotten double J stent. Case report of a multifractured ureter stent. AB - An 81-year-old male patient was admitted to hospital because of macrohematuria. The clinical examination revealed a multifractured double J stent which had been placed 17 months before in another clinic because of hydronephrosis. In the reported case, a combined endoscopic and open surgical management was necessary to remove all fragments from the renal pelvis, the ureter and the bladder. Occlusion, encrustration and migration are among the most frequent risks of ureter stenting. The breakage of the stent, however, is a rare but severe complication. Therefore, patients should generally be controlled by sonography every 2 months and when malfunction of the stent is suspected, a cystogram should follow. In general, a stent exchange should be performed after 12 months. PMID- 1441013 TI - Delayed dehiscence of repaired bladder rupture. AB - A case of dehiscence of a previously repaired bladder rupture occurring 3 years after the original repair is reported. There was no obvious predisposing cause to this event. As this occurrence is very rare, it brings into question the need for long-term review of patients with conservatively treated bladder rupture. PMID- 1441014 TI - Penile horn. AB - A case of cutaneous horn of the penis is reported, which was treated by electrosurgical excision. The possible etiopathogenesis with a review of the literature is discussed herein. PMID- 1441015 TI - Diagnostic and predictive value of an immune monitoring program for complications after kidney transplantation. AB - We have tested an immune monitoring program consisting of cytofluorometric analysis of lymphocytic and monocytic markers, using a set of different monoclonal antibodies (mAb), in about 500 transplant patients including about 300 long-term renal allograft recipients. The high sensitivity (95%) of these cytofluorometric analyses in the peripheral blood allows to discriminate between acute rejection and other causes of deteriorated kidney transplant function (infection, toxicity, arteriopathy), especially in the late phase (> 1 year) after transplantation. Additionally, the immune monitoring is sufficient to predict success of antirejection therapy as early as a few days after onset of treatment. A life-threatening complication in allograft recipients is septic disease. Proceeding from immune parameters, septic patients were found to fall into two categories: those with decreased expression of HLA-DR on monocytes (< 20%, termed as 'immunoparalysis') and patients with nearly normal HLA-DR+ monocytes. Septic immunoparalysis requires drastic reduction of immunosuppression (mortality after drastic reduction: 8%; after marginal reduction or without reduction: 90%). We have not observed severe rejection as a consequence of reduced immunosuppression in such patients. Our immune monitoring seems to be useful for management of immunosuppression in patients with unclear deterioration in graft function as well as patients with septic complications in order to minimize two risks, i.e. death by sepsis or loss of graft. PMID- 1441016 TI - Problems of the distal ureter in renal transplantation. AB - The incidence and mortality rates of urologic complications in renal transplantation have decreased significantly during the last decade. This was achieved by improved techniques of donor nephrectomy with preservation of the ureteric blood supply and refined procedures for the reconstruction of the urinary tract. Intra- and extravesical ureteroneocystostomies have shown to be the most reliable and preferred techniques to restore the urinary tract continuity. Beside ureteral ischemia and technical failure ureteral rejection is increasingly accepted as an important contributory factor for the development of ureteric fistula and stenosis formation. Controversy still exists concerning the pathogenesis of reflux into the graft and its impact on long-term graft function. Percutaneous and endoscopic procedures have supplemented and partially replaced open surgical management of ureteric fistulas and stenoses. By adherence to the principles described the frequency of urologic complications and its associated mortality rates can be minimized. PMID- 1441017 TI - Secondary pyeloureterostomy after ureter necrosis in renal transplant recipients. AB - After kidney transplantation, urological complications account for significant morbidity necessitating reoperation in a substantial number of patients. In cases with urinary tract necrosis after renal transplantation secondary pyeloureterostomy represents an accepted method for urinary tract reconstruction. In our institution 2% of all kidney grafts required secondary pyeloureterostomy. In all cases the recipient's own ureter was investigated before reoperation by retrograde pyeloureterography. Pyeloureterostomy was performed with a standard technic, the recipients own kidney being removed in all but 5 patients. All 25 patients had normal kidney function immediately after secondary pyeloureterostomy. Urological complications occurred in 7 patients (anastomotic leakages in 4, stenosis in 3); 5 out of 7 complications were managed conservatively (nephrostomy, transureteral stenting). Two patients needed reexploration for reanastomosis. Our results confirm the simple and safe technic of pyeloureterostomy for urinary reconstruction in patients with ureter necrosis after renal transplantation. PMID- 1441018 TI - Problems concerning the bladder in renal transplantation. Prognosis--replacement possibilities. AB - Problems arising from the lower urinary tract in patients with a terminal renal insufficiency are usually known long before transplantation; they can even be the cause of chronic renal failure. A careful investigation of morphology and function of upper and lower urinary tract before performing renal transplantation is still of great importance. In up to a quarter of the cases pathological findings can be recorded. Whether a supravesical urinary diversion or a bladder augmentation has to be performed in case of insufficient bladder function is dependent on the urodynamic results. However, so far there are no reliable prognostic factors indicating whether or not a bladder with increased capacity due to renal transplantation reacts with normal pressure. An investigation of the lower urinary tract also has to be carried out in patients who already have a supravesical urinary derivation at the time of renal transplantation, as a possible removal always has to be taken into consideration. Survival rate following transplantation in patients with a conduit is not lower than in those with a normal bladder. PMID- 1441019 TI - Diagnosis and treatment of urological complications in kidney transplantation. AB - Between January 1973 and January 1990 we carried out 1,038 kidney transplantations using a transvesical end-to-side implantation of the ureter in the bladder without an antireflux mechanism. Moreover, 30 transplantations were done in 26 patients with a urinary diversion. We examined the urological complications in these 1,068 consecutive transplants. Urinary leakage and obstruction were the two main urological posttransplant complications. Severe leakage occurred in 21 patients (2.0%), and was treated by open surgery; 2 patients had a urinary diversion. The treatment of choice is a pyeloureterostomy (anastomosis between the transplant renal pelvis and the native ureter). There were 35 patients (3.3%) with severe ureteral obstruction of whom 5 had a urinary diversion. In 30 patients open surgical treatment of the obstruction was necessary and in 7 patients a percutaneous endourologic treatment was done (dilatation of a confined ureteral stricture in 6 patients and percutaneous stone treatment in 1). The postoperative mortality in the patients treated for leakage or obstruction was low: 4 patients (7%) died, 3 of septicemia due to leakage and 1 of pulmonary embolism after repair of the obstruction. The results of surgical treatment were good. The graft survival after 2 years in the group of urologically complicated transplants was 68% for the patients with leakage and 80% for those with obstruction. The 2-year graft survival in the patients without complications was 67% and 71% for the patients with a urinary diversion. We conclude from these results that urological complications after renal transplantation can be treated successfully by surgical (or percutaneous) correction. PMID- 1441020 TI - Biochemistry of bladder cancer invasion and metastasis. Clinical implications. AB - In bladder cancer, the finding of infiltration signals the capability of a tumor to behave in an aggressive manner and potentially create a life-threatening situation. The ability to invade is carried in the tumor cell's complement of biochemical pathways as well as in its inability to preserve or restore rather than to disrupt normal tissue architecture. What determines the activation and deployment of these biochemical activities is unclear. That they occur, however, and can distinguish aggressive cancers likely to metastasize from cancers whose behavior is benign, is not. Recognizing and identifying these distinctions is an important step in designing new therapies to prevent a tumor's potential aggressive behavior, possibly reverse or at least contain any extensions that have occurred, and ultimately convert a potentially life-threatening situation to one with a more benign prognosis. PMID- 1441021 TI - Molecular genetics and biochemical mechanisms in bladder cancer. Oncogenes, tumor suppressor genes, and growth factors. AB - Transitional-cell carcinoma of the bladder is believed to arise through a series of genetic changes affecting cell growth and proliferation. Two basic types of such genes have been described: protooncogenes and tumor suppressor genes. The former have not been studied extensively in bladder cancer, although there is evidence that c-erb B-2/neu is overexpressed. Loss of specific chromosomal regions, which is common in bladder tumors, may inactivate tumor suppressor genes, of which p53 has received the most attention. Work also has been done on epidermal growth factor and its receptor, yielding evidence that malignant and normal urothelium have different sensitivities to its action. Although several advances must be made before genetic changes come to the clinical forefront, the information now being gained with such speed holds considerable promise for diagnosis and treatment. PMID- 1441022 TI - Basic epidemiologic and statistical methods in clinical research. AB - Various study designs and approaches to statistical analysis in clinical research have their own underlying rationales and limitations for interpretation. This information is presented in an intuitive and accessible manner, relying minimally on basic algebra. Epidemiologic concepts of study design and interpretation, bias and confounding, hypothesis testing, and sample size and power are explained. Statistical tests and their appropriate applications are discussed for mean comparisons (t tests and ANOVA), percentages (chi-square), survival analysis, and correlation and regression. Applicable nonparametric tests are also introduced. PMID- 1441023 TI - Assessment of study design in clinical trials for bladder cancer. AB - Physicians and surgeons who treat bladder cancer must be able to judge the validity and relevance of clinical trials if they are to make appropriate recommendations to their patients. To do so, they must be familiar with the design of clinical trials and with the many problems that may confound their results and limit their validity. The present article has reviewed aspects of the design, analysis, and reporting of clinical trials with particular reference to bladder cancer. Nonrandomized studies are important in establishing the feasibility of new treatments and in providing preliminary information about effectiveness. However, selection of patients, together with many other types of bias, prevents a useful comparison of the results obtained in such trials with those obtained using alternative treatment strategies. Establishment of the value of a new type of treatment will usually require the conduct of a large randomized trial in which patients receive experimental or standard therapy by random assignment. While such trials may influence practice in an appropriate way, they must likewise be reviewed critically to ensure the validity of the results and generalizability to patients seen in a nontrial setting. PMID- 1441024 TI - Staging of advanced bladder cancer. Current concepts and pitfalls. AB - Data presented in the preceding paragraphs should highlight to the reader several important features of clinical bladder cancer staging. Irrespective of the staging level being addressed, the available techniques uniformly have limitations, as well as advantages and disadvantages with respect to each other. A common shortcoming of both plain and cross-sectional techniques employing conventional X-rays is their lack of specificity. Every radiographic finding has an associated differential diagnosis in which neoplasia-related change is but one of many possibilities. Solitary abnormalities on bone scan or chest film serve as an excellent examples of this dilemma. The specificity of conventional imaging techniques is further compromised by attempts to increase sensitivity. As long as nonspecific anatomic changes are used as discriminating criteria, increases in test sensitivity will always occur at the price of specificity. It is hoped that advances in PET scanning and the use of isotope-labeled, tumor-selective monoclonal antibodies will overcome the limitations of currently available techniques. The significance of the limitations of a given test depends to some degree on whether the test is being used for clinical decision making or for patient stratification in a clinical trial. As an example, an aggressive transurethral resection of bladder tumors provides excellent information for clinical management but may introduce bias into multicenter studies in which this technique is not uniformly practiced. Similarly, the results of bimanual examination under anesthesia are important in the reference framework of the managing physician but are a poor quantifier of disease extent in multi investigator clinical trials. Which staging studies are indicated and their optimal sequence for performance are influenced by pre-existing clinical information. Recognizing this, the staging algorithm in Figure 6 is intended to serve only as a guide to assist the clinician in the evaluation of patients with bladder neoplasms. As clarifications, several points concerning this algorithm merit mention. The literature suggests that as a single study, transurethral ultrasonography provides excellent local staging information. However, given that it is not widely available, the authors have chosen not to incorporate it into the staging schema. Optimally, it would be used immediately prior to transurethral resection of bladder tumors and bimanual examination. In addition, the algorithm lists MRI interchangeably with CT. While MRI appears to have slightly better sensitivity and specificity for both local and regional tumor stage relative to CT, its benefits are to some degree offset by its greater cost and the need to image the patient in multiple planes for lengthy intervals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1441025 TI - Treatment of regionally advanced bladder cancer. An overview. AB - The finding of muscle-infiltrative bladder cancer is generally considered ominous, as 50% of patients who present with this condition are likely to develop distant metastases within 2 years. However, some types of infiltrative bladder cancer appear to have a less ominous prognosis. In order to assess the results of various therapies on regionally advanced bladder cancer, it is important to characterize the distinctions between the types with a poor prognosis (5-year survival rate 15% to 30%) and those with a better prognosis (5-year survival rate 50% to 85%). The former have a nodular architecture, infiltrate more deeply and in a tentacular pattern, and more often involve the bladder wall vasculature and lymphatics than does the latter type, which has papillary architecture and infiltrates on a broad front. These two types appear to respond differently to various treatments except systemic chemotherapy. PMID- 1441026 TI - Transurethral resection in regionally advanced bladder cancer. AB - Various treatments have proved useful for disease control in some patients with regionally advanced bladder cancer. Transurethral resection may cure some patients with invasive disease, but identifying patients with such potential early in their course is difficult. A restaging transurethral resection helps indicate whether conservative management is feasible and, if not, which operation is appropriate. In some patients, transurethral resection may enhance the response to chemotherapy. Research is needed to identify those tumor characteristics associated with good results of conservative management of regionally advanced bladder cancer. PMID- 1441027 TI - Partial cystectomy. AB - Partial cystectomy remains an uncommonly performed procedure in the urologist's armamentarium. Historically, it has had a limited role in the treatment of bladder cancer because of the variable reported success rate and because of the high success rate of local endoscopic excision. When patients with muscle invasive lesions are appropriately selected, 5-year survival rates following partial cystectomy approximate those of radical cystectomy in the treatment of transitional-cell carcinoma while preserving a physiologically functioning bladder. Therefore, not only does partial cystectomy represent a valuable treatment option, but it appears to be the procedure of choice for local muscle invasive transitional-cell carcinoma of the bladder when careful selection criteria are utilized. Future studies are needed to define its precise role in affording bladder preservation when used in association with adjuvant chemotherapy. Partial cystectomy also remains a surgical option for a variety of less common benign and malignant lesions of the bladder. PMID- 1441028 TI - Radiation therapy in regionally advanced bladder cancer. AB - In conclusion, for patients undergoing bladder preservation, conventional external radiation therapy can no longer be recommended as a curative single modality. The usefulness of prognostic indicators, such as radiation responsiveness and tumor morphology, will have to be evaluated in light of newer treatment regimens. Patients should receive external radiation only if other therapies such as hyperfractionation, brachytherapy, intraoperative electrons, or combined chemotherapy and radiation therapy are unavailable or unable to be tolerated. Patients undergoing a planned cystectomy should receive preoperative radiation therapy until such time as neoadjuvant chemotherapy has been proved more or equally effective. PMID- 1441029 TI - Systemic chemotherapy in regionally advanced bladder cancer. Theoretical considerations and results. AB - Integrating systemic chemotherapy into the treatment of patients with invasive bladder cancer, where the majority of deaths are from systemic relapse, is crucial if survival is to be improved. However, the global recommendation of a single treatment approach for all patients is becoming outdated as several groups have found that appropriately selected patients enjoy comparable survival whether treated by transurethral resection alone or by partial or radical cystectomy. Thus, refining case selection becomes a critical area of investigation. Patients with a high risk of systemic relapse should be considered for systemic therapy early in the course of the disease, ideally as part of a clinical trial. The availability of growth factors has reduced the toxicities of the regimens currently in use. Improvements in assessing biologic potential are required, so that treatment recommendations will allow patients the maximal chance of cure and maintenance of organ function, while minimizing toxicities in patients for whom systemic approaches are unwarranted. Of interest are recent reports that G-CSF may enhance tumor sensitivity to methotrexate in vitro and increase the sensitivity of implanted urothelial tumors to chemotherapy in nude mice. Such findings suggest an expanded role for these agents. Unfortunately, simple escalation of all components of a combination regimen does not appear to be a viable strategy, as it is unlikely to significantly increase CR proportions without prohibitive toxicities. However, as more is understood about drug resistance, and in particular its development in vivo, better sequencing of the available of options should be possible. The availability of effective salvage therapies suggests that this is an appropriate therapeutic approach. In addition, a number of strategies aimed at reversing the mdr phenotype are under study. These include calcium channel blockers such as verapamil, cyclosporin, and tamoxifen. Alternatively, some groups are investigating transfecting the mdr gene into bone marrow cells to reduce the sensitivity of these cells to cytotoxic agents. These novel designs can be tested both in patients with metastatic disease and in patients with locally advanced (T3b, T4, and N+) disease, who have a high risk of metastatic failure and low CR proportions to available regimens. PMID- 1441030 TI - Combined treatment approaches in regionally advanced bladder cancer. AB - Multimodal therapy for locally advanced bladder carcinoma is being pursued in a wide diversity of protocols at this same time. While a number of innovative approaches are being explored, neoadjuvant and adjuvant chemotherapy in conjunction with cystectomy remains the dominant approach. The M-VAC regimen has become the dominant combination for the treatment of advanced bladder cancer; its use in an adjunctive setting is a logical progression. Although it is capable of effecting a response in the primary bladder lesion in a high percentage of cases, it is still not known whether survival will be enhanced. The use of radiosensitizing cytotoxics in conjunction with neoadjuvant chemotherapy, when combined with external-beam radiotherapy, is a provocative new approach that attempts to achieve both bladder salvage and enhanced patient survival. Completion of well-designed randomized studies will be necessary to determine whether these therapeutic innovations will yield any clinical benefit. PMID- 1441031 TI - Treatment of chemotherapy-refractory metastatic urothelial tumors. AB - Patients with unresectable bladder carcinoma unresponsive to standard chemotherapy have a short survival, but recent clinical trials of salvage treatment have produced some good results. Changes in the dosage of M-VAC; 5 fluorouracil, alpha-interferon, and cisplatin; and gallium nitrate show promise. PMID- 1441032 TI - Urinary diversion. AB - The patient facing cystectomy now has the opportunity to select various forms of urinary diversion. Although not all of the newer techniques have stood the test of time, preliminary results indicate that these continent diversions should be considered safe and effective. These procedures definitely alter the patient's lifestyle, resulting in a significantly better adjustment to the need for bladder removal. With experience, these procedures can be performed with morbidity rates very similar to those encountered with ileal conduit diversion. As with any procedures, however, appropriate patient selection and surgical training are imperative. PMID- 1441033 TI - Management of advanced bladder cancer in the elderly. AB - Patients over the age of 70 years will become an increasingly important component of uro-oncologic practice. Although few published studies have specifically addressed this population, it is clear that the elderly can expect outcomes similar to younger patients in the management of advanced bladder cancer provided care is taken in planning. Of particular importance is an understanding of the pathophysiology of aging, of the possible implications of the causative factors for bladder cancer, and of the potential impact of advanced age on the biology of urothelial malignancy. Future studies should specifically address the problems of older patients with this malignancy to ensure the optimal possible outcome and definition of the most appropriate balance of toxicity and efficacy. PMID- 1441034 TI - Renal pelvic cancer: a review of 611 patients treated in Illinois 1975-1985. Cancer Incidence and End Results Committee. AB - Renal pelvic transitional cell carcinoma constitutes about 7 percent of all kidney cancer. This report is a summary of 611 Illinois patients with this tumor treated between 1975 and 1985. Overall, the five-year relative survival rate was 62 percent and the observed five-year rate was 48 percent. Stage was a major determinant of survival, as expected, in these cancer patients. The Illinois experience is reviewed and compared with the accumulated literature experience with renal pelvic cancers since 1944. PMID- 1441035 TI - Experience with schistosomiasis in renal transplantation. AB - Schistosomiasis involving the urinary tract has only occasionally been reported in North American literature and rarely from American hospital experience. Chronic infection may result in numerous abnormalities of the urinary tract which may interfere with the function of a transplanted kidney. Our institution has performed a number of renal transplants in patients who are from countries where schistosomiasis is endemic. Six patients in our group had evidence of schistosomal disease during their pretransplant evaluation and were appropriately treated. None of these patients had postoperative complications attributable to the schistosomal disease. We recommend that all patients who are from areas where urinary schistosomiasis is endemic undergo a cystoscopic examination and bladder biopsies in addition to the routine pretransplant urologic evaluation. PMID- 1441036 TI - Objective treatment response to endocrine therapy in metastatic prostate cancer. AB - A ten-year review of 198 patients with Stage D2 prostate cancer identified 13 patients (6.6%) who exhibited objective responses to hormonal treatment, as indicated by regression of a positive bone scan, CT scan, or chest x-ray film. Four patients had complete responses and 9 patients achieved partial responses as judged by the National Prostatic Cancer Project criteria. Median survival for those with objective treatment response has not yet been reached (> 44 months) compared with twenty-four months for the nonresponders (p = 0.00006). Although relatively uncommon, objective treatment response in Stage D2 prostate cancer is correlated with an improved prognosis. PMID- 1441037 TI - Anchor fixation and other modifications of endoscopic bladder neck suspension. AB - The long-term efficacy of surgical treatment of stress urinary incontinence can be improved by modifications that reduce the possibility of suspending suture detachment. Fifty-three women with stress urinary incontinence underwent consecutive endoscopic bladder neck suspensions with new modifications developed in an effort to decrease suspending suture detachment. Those modifications included: (1) technique of needle passage to capture a maximum volume of urethropelvic fascia lateral to the bladder neck and urethra while avoiding injury to the bladder, (2) pubic bone fixation of the suspending suture using a small anchor developed for orthopedic use, and (3) a simple technique to limit tension of the suspending sutures. Procedures were outpatient in 60 percent of patients (93% of the last 27 patients). Seventy percent of patients did not require intermittent catheterization beyond the day when their indwelling catheter was removed. The postoperative success rate (absence of stress urinary incontinence) at one month was 100 percent. There were 4 failures on follow-up up to fifteen months. Urgency incontinence decreased from 59 percent preoperatively to 15 percent postoperatively. The complication of osteitis pubis was not noted. Patient rating of satisfaction postoperatively was high. These modifications constitute a safe alternative to procedures that effectively suspend the bladder neck. An assessment of any change in long-term efficacy as a result of these modifications will require continued follow-up. PMID- 1441038 TI - Penile calcification in maintenance hemodialysis patients. AB - Penile calcification was detected in 6 of 32 patients (19%) with end-stage renal disease (ESRD) using soft tissue x-ray techniques. Having been maintained on hemodialysis for a minimum of one year, all the affected patients showed clinical evidence of secondary hyperparathyroidism and calcification in the blood vessels of some other tissues. All had erectile impotence, while in 1 patient gangrene of the penis developed. Penile calcification is probably more common in ESRD patients than realized and should be looked for as a possible cause of impotence in male patients treated with maintenance hemodialysis. PMID- 1441039 TI - Bladder training in patients with spinal cord injury. AB - Immediately following severe injury to the spinal cord or conus medullaris, there is a stage of flaccid paralysis of the bladder. The smooth muscle of the detrusor and rectum is affected. Drainage of the bladder is very important in the early care of such patients. From August 1989 to August 1990, 55 spinal cord injury patients were studied on admission to our department. The current bladder training method used for these patients is presented. A patient was deemed to have been successfully bladder trained when catheter-free, continent, and able to consistently maintain a residual volume of 100 mL or less with the aid of tapping and compression. On discharge 45 patients (82%) were successfully bladder trained, 8 (15%) employed a regimen of clean intermittent self-catheterization, and 2 went home/institutional care with an indwelling catheter. The material presented is applicable to any type of neurogenic bladder dysfunction. PMID- 1441040 TI - Extracorporeal shock-wave lithotripsy with Lithostar lithotriptor. AB - Initial experience of extracorporeal shock-wave lithotripsy (ESWL) using the Lithostar lithotriptor is reported; 193 patients underwent 248 treatments for 210 stones. A total of 139 renal calculi (126 patients) and 71 ureteral stones (67 patients) were analyzed. Treatments were performed without anesthesia in 65 calculi (27.6%), with intravenous sedation in 91 (42.5%), and under epidural anesthesia in 34 calculi (29.9%). A three-month follow-up showed a success rate of 88.0 percent for renal calculi and 95.5 percent for ureteral calculi treated in situ. Renal stone fragmentation was achieved with a mean of 4,890 shocks at 17.4 kV and ureteral calculi were fragmented with a mean number of 4,798 shocks at a mean of 18.3 kV. Auxiliary procedures after ESWL were required in 2 patients with renal stones and in 1 with ureteral calculi. A comparison between stone size and number of shock waves required to achieve stone fragmentation revealed a linear relationship. Hospitalization was not necessary in 84.4 percent of renal calculi and 89.6 percent of ureteral calculi. Retreatments were necessary in 22 (15.8%) of the renal calculi (18 had 2 sessions, 3 had 3 sessions, and 1 had 4 sessions). Of the ureteral calculi, 8 (11.3%) underwent retreatment (6 had 2 sessions, 1 had 3 sessions, and 1 had 4 sessions). The low morbidity with a large number of patients treated on an outpatient basis, minimizing the need for anesthesia, demonstrated a favorable initial successful experience with the Lithostar. PMID- 1441041 TI - In utero detection of horseshoe kidney with unilateral multicystic dysplasia. AB - Unilateral renal dysplasia in a horseshoe kidney is very uncommon. A case which was detected in utero is presented. The management of multicystic kidneys is reviewed. PMID- 1441042 TI - Klinefelter's syndrome with prepenile scrotum. AB - Two cases of Klinefelter's syndrome with prepenile scrotum were presented. They underwent the operation for prepenile scrotum according to Glenn and Anderson's method. Thereafter urethroplasty was performed in each case. The decrease in response to testosterone in the target organ was noticed in 1 patient, suggesting that some androgen resistance in this case was attributable in part to anomaly of genitalia. PMID- 1441043 TI - Tunica vaginalis urethroplasty. AB - Tunica vaginalis on a vascular pedicle was tubularized and used as a urethra to repair hypospadias in three difficult cases. This is the first report of tunica vaginalis utilized for a urethral reconstruction in humans. This new surgical technique is described. PMID- 1441044 TI - Efficacy and tolerability of norfloxacin vs. ciprofloxacin in complicated urinary tract infection. AB - This prospective, open, randomized clinical study compared the efficacy and tolerability of norfloxacin and ciprofloxacin in adult patients with complicated urinary tract infection, defined as infection in the presence of an underlying anatomic or functional abnormality of the urinary tract. Seventy-two patients were randomized, 37 received norfloxacin (400 mg orally twice daily for 10-21 days) and 35 received ciprofloxacin (500 mg orally every 12 hours for 14-21 days). Patients were clinically assessed, and urine cultures were obtained following two to four days of therapy, and five to nine days and four to six weeks after discontinuation of therapy. Seventy-two percent of the norfloxacin group and 79 percent of the ciprofloxacin group were considered cured. This difference was not significant. One failure of norfloxacin therapy was associated with the emergence of resistant Pseudomonas aeruginosa. Following norfloxacin therapy, in 2 patients superinfections developed with resistant organisms (Staphylococcus epidermidis [1] and Pseudomonas maltophilia [1]). Twelve patients, 6 in each group, experienced adverse reactions, which were considered related to the study drug therapy in only four instances. Our results indicated comparable efficacy and tolerability of norfloxacin and ciprofloxacin in the treatment of complicated urinary tract infection in adults. PMID- 1441045 TI - Arteriovenous malformation of ureter. AB - Congenital arteriovenous malformations of the genitourinary tract are rare. We report the first case of an arteriovenous malformation of the ureter. The patient presented with recurrent hematuria and left flank pain. Evaluation included an intravenous urogram, cystoscopy, and retrograde pyelography. A pedunculated lesion thought to be a fibroepithelial polyp was seen at the time of ureteroscopy, and the lesion treated by excisional biopsy and fulguration. Pathologic examination demonstrated an arteriovenous malformation. After thirty month follow-up, the patient remains asymptomatic and free of recurrence. PMID- 1441046 TI - Metastatic prostate cancer presenting as obstructive jaundice. AB - Metastatic cancer of the prostate, presenting with carcinomatous obstruction of the common bile duct as a cause of jaundice and abnormal liver function tests is very unusual. The literature suggests an association between abnormal liver function tests and poor survivability in those patients with liver parenchymal metastases. This case illustrates that patients with abnormal liver function tests on the basis of extrahepatic ductal obstruction may have a better prognosis than those with hepatic disease. PMID- 1441048 TI - New endourologic technique for catheter placement after TURP, prostatectomy, and difficult urethroscopy. AB - Inserting a Foley catheter into a traumatized urethra with false channels or a post-transurethral resection of prostate (TURP) undermined bladder neck can be very difficult if not impossible at times. Likewise, replacing a Foley catheter that has fallen out in the early postoperative period after a radical prostatectomy can be difficult and can cause significant injury to the fresh anastomosis. We describe a technique using a Peel-Away sheath that fits over a cystoscope or a resectoscope, and facilitates accurate insertion of a Foley catheter without trauma to the urethra. PMID- 1441047 TI - Squamous cell carcinoma of ureter extending into renal vein. Positive immunohistochemical staining for carcinoembryonic antigen. AB - A case of squamous cell carcinoma of the ureter with extension into the renal vein is presented. Immunoperoxidase method revealed positive staining for carcinoembryonic antigen. The literature on ureteral tumors is reviewed with special reference to renal vein involvement and carcinoembryonic antigen. PMID- 1441049 TI - Incidence of testicular microlithiasis. AB - In adults polytopic intratubular calcifications of the testes are rare. Known as testicular microlithiasis, they manifest themselves in a characteristic echo pattern on sonography with high-frequency transducers (5 to 10 MHz). This consists of multiple echogenic specks in an otherwise normal testicular parenchyma. In a retrospective analysis of 1,710 testicular sonograms of adults, bilateral intratesticular microliths were found in 11 cases (0.6%). In 5 of them, the microliths were associated with a testicular tumor. One patient with a tumor in the contralateral testis had undergone radiotherapy and another one presented with hypogonadism. Four patients with noncontributory histories presented with varicocele or epididymal cyst. Sonographic findings were confirmed histologically in 6 patients. Multiple intratubular calcifications were found in all of them. The pathogenesis of testicular microliths is still poorly understood. Their clinical relevance is unclear, but their incidence in adults appears to be higher than reported in the literature. PMID- 1441050 TI - The vas after vasectomy: comparison of cauterization methods. AB - A histologic study of the vas ends was carried out in 21 patients undergoing vasovasostomy. All had undergone prior vasectomy by the same surgeon, with a technique identical except for the type of cautery used to seal the vas ends. A superior sealing of the vas, as shown by fewer cases of vasitis nodosa and spermatic granuloma, followed use of the thermal cautery ("red-hot wire") than the electrosurgical cautery (23% vs 60.7% suboptimal sealing rate). The thermal cautery is a superior method of sealing the vas at vasectomy. PMID- 1441051 TI - Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation. AB - We investigated the relaxant effect of electric field stimulation (EFS) on rabbit cavernous smooth muscle strips in vitro precontracted by phenylephrine. Effects of EFS were monitored alone, and following muscarinic receptor blockade, and inhibition of nitric oxide (NO) formation by L-N-monomethylarginine (L-NMMA) or by L-N-nitroarginine (L-NOARG). Atropine only slightly reduced the relaxant effect of EFS to 89.0 +/- 6.1 percent. Additional application of L-NMMA further reduced the relaxant effect to 37.3 +/- 15.3 percent. Substitution of L-NOARG for L-NMMA led to a more pronounced inhibition of relaxant effects to 16.2 +/- 8.7 percent. The results indicate that neurogenically induced relaxation of rabbit cavernous smooth muscle is mediated mainly by NO formation and argue against a substantial role of relaxing peptidergic neurotransmitters, such as vasoactive intestinal polypeptide and calcitonin-gene-related peptide, in penile erection. PMID- 1441052 TI - Squamous cell carcinoma-associated antigen in uroepithelial carcinoma. AB - We investigated the clinical significance of squamous cell carcinoma (SCC) antigen determined by radioimmunoassay on patients with uroepithelial carcinoma. Serum SCC antigen levels and the positive rates were significantly higher in uroepithelial carcinoma having an SCC component than in normal controls, benign urologic diseases, other urogenital carcinomas, or in pure transitional cell carcinoma (TCC) of uroepithelial carcinomas. A substantial number of patients with pure TCC showed a positive serum level of SCC antigen. Immunohistochemical staining of SCC antigen on the uroepithelial carcinomas confirmed that some, not all, pure TCC, mostly grade 3, expressed SCC antigen in their cells. These results suggested a biologic characteristic of grade 3 TCC which is closely related to that of SCC. The serum levels of SCC antigen correlated well with the disease extensions in uroepithelial carcinoma containing SCC component. Changes in serum levels of SCC antigen following treatment reflected the clinical courses of patients, particularly in those with elevated pretreatment levels. The results of our study indicated that the determination of SCC antigen would be clinically useful for monitoring clinical courses of patients with uroepithelial carcinomas containing SCC component and of those with pure TCC whose pretreatment level was elevated. PMID- 1441053 TI - IgM-producing renal plasmacytoma. AB - A seventy-six-year-old woman with plasmacytoma presenting as a renal mass died three months after diagnosis. Bone surveys disclosed no lytic lesions. Gallium-67 scan showed an avid uptake of the radionuclide in the renal mass. Histologic and immunofluorescence studies of resected specimens demonstrated that the renal parenchyma was destroyed by sheets of immature plasma cells producing IgM-lambda and by massive deposits of amorphous, eosinophilic substance stained with anti-mu and anti-lambda antisera. The literature is reviewed. We believe this case is the first one of well-documented IgM-producing renal plasmacytoma. PMID- 1441054 TI - [Development of standards and quality assurance in nursing activities--Finland]. PMID- 1441055 TI - [Development of standards and quality assurance in nursing--Iceland]. PMID- 1441056 TI - [Development of standards and quality assurance in nursing services--Norway]. PMID- 1441057 TI - [Development of standards and quality assurance in nursing services--Sweden]. PMID- 1441058 TI - Patient satisfaction as an indicator of the quality of nursing care. AB - This paper deals with the patient satisfaction, as an indicator of the quality of nursing care. The literature review and a Finnish empirical illustration, using patient interviews, are included in the article. The results indicate a high level of satisfaction. However, there is no basis to use the measurement of patient satisfaction as a sole indicator of the quality of care, because the satisfied patients expressed also reasons for dissatisfaction. PMID- 1441059 TI - [The concept of quality in nursing and nursing services]. PMID- 1441060 TI - [Scandinavian cooperation in quality assurance in nursing]. PMID- 1441061 TI - [SSN's Study Group "Standard and quality in nursing services" (Scandinavian Nursing Society)]. PMID- 1441062 TI - [Measuring nursing care quality. Adaptation and testing of the Rush Medicus Process instrument]. PMID- 1441063 TI - Measurement of outcomes. PMID- 1441064 TI - [Administration's role in quality assurance in nursing services]. PMID- 1441065 TI - [Development of standard and quality assurance in nursing--Denmark]. PMID- 1441066 TI - [Freedom as an occupation]. PMID- 1441067 TI - [Reopening chronic arterial occlusions]. AB - Chronic complete occlusions still represent the major technical limitation of percutaneous transluminal balloon angioplasty, both in peripheral and coronary vessels. The clinical use of low speed rotational angioplasty (ROTACS) started in 1986 for the peripheral and in 1987 for the coronary vessels, and has already become part of the clinical routine in several centers. Up to now, more than 300 patients with peripheral and more than 200 patients with coronary occlusions were treated in Frankfurt. In peripheral occlusions the acute success rate was more than 80% if used as the first attempt; after failure of conventional techniques still more than 60% of the vessels could be recanalized successfully. In addition to occlusions of the arteries of the lower limbs, the indication now includes the iliac artery and several other indications are under investigation. In each of the patients with chronic coronary occlusions an attempt with conventional techniques had failed before. Following a learning curve, which was also influenced by a better understanding of morphological preconditions, the acute success rate has now reached 70%. Both in patients with peripheral and those with coronary occlusions no deaths occurred. First angiographically documented long term results in both indications are comparable to conventional balloon angioplasty. It is concluded that the use of low speed rotational angioplasty (ROTACS) can improve the results of nonoperative invasive treatment, both in peripheral and in coronary arteries. PMID- 1441068 TI - [Coronary vascular stent implantation--experiences with the first 100 implants]. AB - Coronary stent implantation was performed for blocking elastin recoil, reducing acute complications and restenosis. In 89 (95%) of 91 patients successful stent implantation was possible. No stent embolization occurred. Coronary luminal diameter measured 1.05 +/- 0.57 before PTCA and 1.9 +/- 0.2 mm post PTCA. After stent implantation mean diameter of the coronary artery measured 3.05 +/- 0.2 mm, with a balloon diameter of 3.0. Thus, elastic recoil is nearly completely blocked. In 28 (31%) of 91 patients stent implantation was performed for acute symptomatic dissection in 27 patients and occlusion in one patient. Stent delivery was successful in all. There was no acute occlusion, one acute thrombosis which could be treated with urokinase, no Q-wave-infarct, 4 (14%) non Q-wave-infarcts and 14 (20%) CK-elevations without ECG changes. Coronary bypass surgery was necessary in 2 patients on an elective base during follow-up. In 72 (90%) of 80 patients follow-up coronary angiograms after 4 to 6 months were performed. Restenosis rate measured 21% overall, 14% for single stent, 60% for multiple stent implantation, and 14% in bail-out situations. Subacute thrombosis occurred in 10 (12%) of 89 patients, 7 (70%) of 10 events after bail-out stenting. Recanalization by thrombolytic and/or PTCA was possible in 9/10 patients. By improving monitoring of anticoagulation, the subacute thrombosis rate could be reduced to 3% even in bail-out situations. Bleeding complication occurred in 10% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441069 TI - [Long-term results of coronary angioplasty]. AB - Recently published studies prove a favourable long term prognosis after coronary angioplasty, especially in patients with single vessel disease. PTCA success, progression of atherosclerosis, cardiac risk factors, extent of coronary artery disease and left ventricular function are determinants of the long term outcome. A lasting PTCA success can be assumed in patients without evidence of restenosis 6 months after PTCA. These observations are helpful criteria in the assessment of insurance risks. PMID- 1441070 TI - [Results of heart valve replacement. Prognosis--occupational and general disability--occupational rehabilitation]. AB - The success of valve surgery has led to a marked improvement in prognosis, quality of life and exercise tolerance in patients with symptomatic valvular heart disease. The degree of subjective and objective improvement depends on multiple preoperative factors like NYHA status, left ventricular function, valve lesion and type of valve replaced as well as peri- and postoperative factors like the occurrence of a perioperative myocardial infarction, the degree of intraoperative myocardial damage, the type of valve replaced and the speed and degree of postoperative regression of left ventricular hypertrophy and dilatation. The postoperative exercise tolerance is a major determinant for postoperative vocational rehabilitation. Therefore the individual functional assessment of patients postoperatively is of major importance. PMID- 1441071 TI - [Therapy with nitrates in the post-infarct phase]. AB - The beneficial effects of nitrates in patients with angina pectoris and acute myocardial infarction have positively influenced the prognosis of the treated patients. Studies of Jugdutt pointed out that there is a better prognosis also in the postinfarction period. Especially left ventricular over dilatation, which follows larger infarct, can be prevented by a consistent nitrate therapy. PMID- 1441072 TI - [Diagnosis of acute coronary ischemia]. AB - In patients presenting with acute chest pain and suspected acute coronary insufficiency the diagnosis and the decision to admit such patients to a coronary care unit is based on the history, the physical findings and the first electrocardiogram. A diagnostic flow diagram can complement but not substitute clinical judgement. PMID- 1441073 TI - [Accusation of malpractice in cardiovascular surgery]. AB - The reproach of malpractice in cardio vascular surgery seems to be up to now quite seldom in comparison with other While in cardiac surgery the acknowledgement was found extremely seldom in vascular surgery acknowledgement of malpractice reproach must be expected in about 50%. In cardiac surgery mainly new neurological deficits are content of malpractice reproach; in vascular surgery artery injuries and surgical procedures to correct varicose veins are most often involved. In order to prevent or to minimise those malpractice reproaches an optimal communication between the surgeon and the patient, an extensive informed consent and a very strict medical indication for surgery are imperative. PMID- 1441074 TI - [Evaluation of occupational and work capacity after myocardial infarct]. AB - Innovations in medical technics increase in volume. In consequence the medical expert has more difficulties in judging the rank of the different tests and medical examinations. With this publication we intend to help to value the results of specific medical tests and the checkup of a patient after a myocardial infarction with regard to the "Berufs- und Erwerbsunfahigket". Furthermore there is a table, showing criterions and various results to answer the question, if a patient after a myocardial infarction is able to have furthermore an occupation and if you may expect heavy labour of someone. In this article, written by a doctor working in a hospital treating patients with diseases of the heart circulation system, special aspects were considered, concerning the "Anschlu ss heilbehandlungsma ss nahme", which is a common practice for a patient after a myocardial infarction. PMID- 1441075 TI - [Comment on the contribution by Dr. N. A. Sittaro: Problems and compensation of back and spinal disorders in workman's compensation]. PMID- 1441076 TI - [The treatment of malignant tumors of the ethmoidal labyrinth]. PMID- 1441077 TI - [The differential diagnosis of Meniere's disease and neurinoma of the 8th nerve]. PMID- 1441078 TI - [The treatment of patients with allergic rhinosinusopathy]. PMID- 1441079 TI - [The significance of the structural characteristics of the sphenoid sinuses in the development of sphenoiditis]. AB - Medicolegal autopsies show a great incidence of sphenoiditides (63.3%) with a prevalent chronic atrophy (48%). Frontal and asymmetric presentation of the posterior cribrate cells about the sphenoid sinuses proved an unfavorable regional anatomic factor underlying dysfunction of the shunt drainage. Sphenoiditides are also promoted by digestions of the Vidian nerve canal producing harbours at the base of the sphenoid pterygoid process. Identification of anatomical factors of risk and characterization of the mucosal defects can be conducted at additional x-ray examination. PMID- 1441080 TI - [The endoscopic CO2 laser surgery if congenital laryngeal synechiae]. PMID- 1441081 TI - [The clinico-diagnostic and therapeutic aspects of ENT organ involvement in patients with mucoviscidosis]. PMID- 1441082 TI - [The clinico-anatomical basis for sectioning the vidian nerve]. AB - Regional anatomic study of the pterygopalatine fossa on 101 cadavers, 86 angiographies, 114 x-ray tomography pictures provided evidence in support of the advantages of the Nomure transantral subperiosteal approach to the vidian nerve. To prevent postoperative complications, the nerve destruction was carried out by laser. The power and exposure were tested on 15 white rats. Seventy surgical interventions were performed in the clinic of ENT diseases of the Leningrad Medical College. Their results were assessed with specially devised techniques. The authors thought the cut of the vidian nerve an effective procedure in chronic polypous rhinosinusitis as it brought about a persistent response and improved the condition of the nasal mucosa. PMID- 1441083 TI - [The treatment of exudative forms of maxillary sinusitis in children with complete closure of the natural opening]. PMID- 1441084 TI - [An esthesioneuroblastoma of the nasal cavity and paranasal sinuses]. PMID- 1441085 TI - [The use of local oxygenation with one-time perfusion in treating exudative maxillary sinusitis]. PMID- 1441086 TI - [The free transplantation of a part of the concha auriculae in a defect of the ala nasi]. PMID- 1441087 TI - [Lethal midline granuloma]. PMID- 1441088 TI - [The procedure for treating patients with chronic suppurative otitis media depending on the nature of the microflora]. PMID- 1441089 TI - [A foreign body in the frontal lobe]. PMID- 1441090 TI - [A rhinolith with a nucleus from the remains of a gauze tampon]. PMID- 1441091 TI - [The long-term presence of a foreign body in the larynx]. PMID- 1441092 TI - [An analysis of patient mortality based on the data from the ENT Department of the M. F. Vladimirskii Moscow Province Clinical Research Institute for a 12-year period (1979-1990)]. PMID- 1441093 TI - [Studies in the history of radical ear surgery (for the centenary of its development)]. PMID- 1441094 TI - [Endaural surgery in children]. PMID- 1441095 TI - [The diagnosis of malignant neoplasms of the naso- and oropharynx by using computed magnetic resonance tomography in an ultralow field]. AB - MR tomography examination of 51 patients with maxillofacial or cervical cancer provided adequate diagnostic information especially in the absence of bone involvement. The method proved efficient in differentiating tumors with inflammation, in tumor localization, evaluation of its size and spread, outline, structure, invasion. It is safe, noninvasive. For differential purposes the technique is most beneficial in impulse double echo mode with proton density and T2. PMID- 1441096 TI - Parasitic otitis in sheep associated with psoroptes infestation: a clinical and epidemiological study. AB - Parasitic otitis associated with psoroptes infestation was diagnosed in a small pedigree flock of sheep with aural haematomas, abscessation and cauliflower ears. Thirteen of the 15 lambs were affected but the clinical signs were mild; small, discrete, crusty lesions on the inner aspect of the ear at the junction of its anterior and posterior borders were typical. Nine of the 20 adults were affected but the lesions were more severe. Eighteen of the 64 members of the breed society who responded to a telephone survey reported sheep with similar clinical signs in their flocks. The proportion of animals affected ranged from 1 to 60 per cent with a median value of 16 per cent. PMID- 1441097 TI - Incidence and clinical significance of sesamoid disease in rottweilers. AB - A group of 55 rottweiler pups was studied from three to 12 months old to assess the incidence and clinical significance of disease involving the palmar metacarpal sesamoid bones. The results of physical examination were correlated with clinical signs of lameness and the results of radiographic examination of the forefeet. Twenty-one dogs became lame during the study and in 12 of them the lameness was attributable to sesamoid disease. However by 12 months of age, the incidence of sesamoid disease as assessed by radiographic changes in the sesamoid bones was 73 per cent (30 of 41 dogs). Six of the 12 dogs which were lame owing to sesamoid disease got better without specific treatment. It was concluded that sesamoid disease can result in clinical lameness in young rottweilers, but that subclinical disease is common. PMID- 1441098 TI - A clinical trial of buparvaquone in the treatment of East Coast fever. AB - A clinical trial was conducted to test buparvaquone (Butalex; Coopers Pitman Moore) in the treatment of East Coast fever under field conditions in Kenya. Data from 229 cases were analysed following treatment with one (69), two (142) or three (18) doses at 2.5 mg/kg. The majority of cattle (95.2 per cent) were exotic (Bos taurus) or improved (Bos taurus cross Bos indicus) and 39.3 per cent were infected with Anaplasma marginale. There was an overall recovery rate of 85.6 per cent, with 90.1 per cent recovering following one treatment and 75.4 per cent recovering following two treatments. At a follow-up visit three to six months after completion of the trial data was obtained on 224 cases. Thirty had died, 13 of which were reported to have been from East Coast fever, nine had been sold and six slaughtered. Of the remaining 146, 86.3 per cent were in good condition, 13.7 per cent fair and 2.0 per cent in poor condition. A two dose regimen was most effective and should be recommended except in very early cases or those under direct veterinary supervision. PMID- 1441099 TI - Hemivertebra in a crossbred heifer. PMID- 1441100 TI - Docking of dogs. PMID- 1441101 TI - Suspected European brown hare syndrome in Scotland. PMID- 1441102 TI - Welfare of farmed fish. PMID- 1441103 TI - Erosion of veterinary influence. PMID- 1441104 TI - Euthanasia of horses. PMID- 1441105 TI - Measuring dairy herd fertility. AB - The use of the calving index as a measure of herd fertility ignores the proportion of the herd that is culled, generally for failing to conceive. It is more important to consider the total cost of long calving intervals, high culling rate and even low pregnancy rates in an integrated index that reflects inefficient management, than to have to cope with balancing a number of separate physical indicators. In a study of 91 herds containing 14,524 cows a full range of physical indices was examined. The average herd calving interval was 380.3 days, with a culling rate of 23.1 per cent. Of the cows calving, 76.9 per cent recalved, a figure which when adjusted for the calving interval (CIA calving rate) became 73.8 per cent. In quartiles split on the basis of CIA calving rate, the top quartile achieved 82 per cent with a calving index of 375.2, and a culling rate of 16.7 per cent. These standards were achieved by serving 91.9 per cent of the cows after calving, at an interval to first service of 67.2 days. The submission rate for artificial insemination in the first 24 days after the earliest service date was 57.5 per cent and the overall pregnancy rate was 51.2 per cent. As a result 92.1 per cent of the cows served, and 85.3 per cent of those which calved, conceived again, with an average of 1.9 services per conception. Assessing fertility on a financial basis, with costs attributed to calving interval, culling rate and pregnancy rate to give a fertility index, the average herd was losing pounds 62/cow/year, compared with target levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441106 TI - Farm investigations of anaemia in lambs caused by feeding cow colostrum. AB - The deaths on nine farms of lambs which had been fed cow colostrum as a substitute for ewe colostrum were investigated. Of 105 lambs which received cow colostrum, 65 (61.9 per cent) showed clinical signs of anaemia and 42 (40 per cent) died. The signs of anaemia usually appeared when the lambs were between eight and 12 days old. The most significant post mortem finding was the appearance of the bone marrow which was cream or grey rather than the normal bright red. The types of treatment which were given are summarised. Whey from samples of the colostrum fed to the lambs was tested for its effect on sheep red blood cells. Haemolysis or agglutination of the red cells occurred with some, though not all, of the samples which caused anaemia. PMID- 1441107 TI - Ataxia and head tremor in an alpaca (Lama pacos) AB - An 18-month-old alpaca developed nervous signs, including swaying of the head and neck, a wide-based stance and hind-limb ataxia. No certain diagnosis was made but the animal recovered after successive treatment with amoxycillin, vitamin B1, ivermectin and copper oxide, followed by vitamin E and selenium. The differential diagnosis rationale of treatment is described. PMID- 1441108 TI - Observations on the epidemiology of Taenia hydatigena in Soay sheep on St Kilda. PMID- 1441109 TI - Efficacy of netobimin against naturally acquired helminth infections in cattle. PMID- 1441110 TI - 'Superfleas' bounce back? PMID- 1441111 TI - Use of free-access minerals. PMID- 1441112 TI - Respiratory mucociliary clearance in the horse in health and disease, and its pharmaceutical modification. AB - The structure and possible functions of respiratory secretions are reviewed. In the equine, goblet (mucus producing) cells are the main source but little information is available on the volume or composition of equine respiratory secretions. Airway mucus has complex and incompletely understood physical characteristics which can be partially assessed by a wide range of in vitro and biological techniques. The complex relationship between mucus structure and its propulsion by the airway cilia are discussed, both in health and with pulmonary disease. Mucokinesis in the horse has been assessed visually, by bronchoscopically observing intratracheal markers and also by the use of radiographic and radioactive markers. All techniques indicate a tracheal mucus velocity of approximately 20 mm/min. A large number of mucokinetic agents have been claimed therapeutically to increase mucokinesis, using a range of mechanisms. These include mucus diluents, surface acting agents, mucolytics, bronchomucotropic agents, ciliary augmentors and broncho-dilators. A critical review of the literature shows that the bronchodilator clenbuterol is the most effective mucokinetic agent assessed to date in the equine. PMID- 1441113 TI - An interlaboratory trial of a latex agglutination kit for rapid identification of Salmonella enteritidis. AB - An interlaboratory trial was conducted of a latex agglutination kit for the rapid identification of Salmonella enteritidis, to assess the stability of the components and its performance with respect to a panel of three coded salmonellas and 243 field isolates. Two of the components of the kit deteriorated with time. All 62 isolates of S enteritidis were correctly identified by the kit; only two false positives were recorded and no false negatives. PMID- 1441114 TI - Use of amoxycillin by injection in Atlantic salmon broodstock. PMID- 1441116 TI - Swine vesicular disease in the European Community. PMID- 1441115 TI - Virginiamycin susceptibility of Serpulina hyodysenteriae, in vitro and in vivo. PMID- 1441117 TI - Control of fleas. PMID- 1441118 TI - Distemper in Grimsby. PMID- 1441119 TI - Exclusions in pet insurance. PMID- 1441120 TI - Use of free-access minerals. PMID- 1441121 TI - Injuries from air-guns. PMID- 1441122 TI - Injuries from air-guns. PMID- 1441123 TI - Progressive axonopathy in boxer dogs. PMID- 1441124 TI - Resistance in goat lice. PMID- 1441125 TI - Prevalence of anthelmintic-resistant nematodes in fibre-producing goats in Scotland. AB - Six cashmere goat herds in Scotland were surveyed to assess the prevalence of anthelmintic resistance and the species of nematode involved. Resistance was determined in vivo by a faecal egg count reduction test and in vitro using an egg hatch assay and specific faecal egg identification techniques. Benzimidazole resistance was present in five of the herds, insufficient eggs were obtained from the other herd to draw firm conclusions. Teladorsagia (Ostertagia) species predominated in four of the five herds in which resistance was detected and Haemonchus contorus was the dominant species in the other. PMID- 1441126 TI - Morbillivirus infection in two common porpoises (Phocoena phocoena) from the coasts of England and Scotland. AB - Two common porpoises (Phocoena phocoena), one found stranded on the Isle of Sheppey, Kent, and the other in the Moray Firth, Scotland, in late 1990, were examined post mortem. Lesions of diffuse bronchointerstitial pneumonia were present in both animals; they were characterised by the infiltration of alveoli with leucocytes, macrophages and multinucleate syncytia, the necrosis of bronchial and bronchiolar epithelium, focal proliferation of type II pneumocytes and occasional acidophilic cytoplasmic inclusions in alveolar macrophages and syncytia. Lymphoid depletion was apparent in the spleen, thymus and lymph nodes of both porpoises. Other changes in the Isle of Sheppey porpoise included severe dacryoadenitis. Marked pharyngitis, oesophagitis and balanoposthitis were present in the Moray Firth porpoise. Immunoperoxidase staining revealed the presence of morbillivirus antigen in a range of epithelia from both porpoises. This is the first report of morbillivirus infection in cetaceans from the coast of Great Britain. PMID- 1441127 TI - Detection of post partum ovarian activity in cows using on-farm progesterone ELISAs. PMID- 1441128 TI - Homoeopathic prophylaxis. PMID- 1441129 TI - Homoeopathic prophylaxis. PMID- 1441131 TI - Aleutian disease in ferrets. PMID- 1441130 TI - Homoeopathic prophylaxis. PMID- 1441132 TI - Licensed veterinary products. PMID- 1441133 TI - Progress in the British hypodermosis eradication programme: the role of serological surveillance. AB - The British warble fly eradication programme has resulted in the numbers of infested cattle falling from an estimated four million in 1978 to zero in 1991. In 1982, when about 705 herds were infested the disease was made notifiable, and serological surveillance was begun in 1988. In spring 1991, 227,000 blood samples were tested by using the ELISA technique and no warbled animals were found. In addition no clinical cases were reported during 1991. PMID- 1441134 TI - Proliferative osteitis of the femoral greater trochanter and humeral medial epicondyle as a cause of lameness in sows. AB - Thirteen chronically lame female breeding pigs were examined clinically and post mortem. Of the eight sows with hindleg lameness, one showed detachment of the ischial tuberosity and a second showed detachment of the ischial tuberosity on the left and a mid-shaft femoral fracture on the right. Two showed no lesions apart from a change in the positional relationship between the femoral head and the greater trochanter, resulting in a lowering of the femoral head. In the remaining four sows an apparently unreported condition was seen, which produced a proliferative osteitis of the greater trochanter. All five animals lame in the forelimb showed varying degrees of proliferative osteitis of the medial epicondyle of the humerus. Advanced cases could be palpated in the live animal. It is proposed that proliferative osteitis may be a response, at the point of attachment of the muscle masses of the major limbs, to the trauma of over exertion. PMID- 1441135 TI - The cost of summer mastitis. AB - The incidence of summer mastitis on 95 dairy farms in southern England was monitored in the summer of 1987. Data on the type of animal infected, the fate of the animals immediately and over the succeeding lactation, and the procedures used in treating the infections were collected for 144 cases. Twenty-five per cent of cases were attended by veterinary surgeons. Most of the animals received parenteral antibiotics and on average each received five tubes of intramammary antibiotic. The incidence of infection was highest in pregnant and calving heifers, more than 2 per cent of the animals at risk, and lowest (0.04 per cent) in calves, although more than twice as many dry cows were infected. Over half of the farms reported summer mastitis, with 36 per cent suffering more than one case. The greatest economic loss, 49 per cent of the total, was from lost milk production; and 37 per cent was from lost animal value, cull and calf losses. The average loss was 192 pounds per case. Using national incidence data from England and Wales, the cost to the UK dairy industry in 1987 was 6.22 million pounds. PMID- 1441136 TI - Benzimidazole resistance in Trichostrongylus axei in Australia. PMID- 1441137 TI - Virulent Serpulina hyodysenteriae from a pig in a herd free of clinical swine dysentery. PMID- 1441138 TI - Exclusions in pet insurance. PMID- 1441139 TI - More than a flea killer? PMID- 1441140 TI - Cattle as a source of verotoxigenic Escherichia coli O157. PMID- 1441141 TI - Diagnosis of snakebite. PMID- 1441142 TI - Unseasonal twins. PMID- 1441143 TI - A neuropathological survey of brains submitted under the Bovine Spongiform Encephalopathy Orders in Scotland. AB - Bovine spongiform encephalopathy was not confirmed histologically in 225 of 829 bovine brains submitted for diagnosis. Several previously described disorders of the central nervous system were observed in these brains as well as disorders not previously recognised in Britain, including bilateral vacuolation of the substantia nigra, hippocampal sclerosis with brainstem neuronal chromatolysis and necrosis, focal symmetrical encephalomalacia and meningio-angiomatosis. Severe cerebellar dysplasia consistent with pre-natal bovine viral diarrhoea--mucosal disease virus infection or mineralisation of the blood vessels of the basal ganglia were interpreted respectively as congenital changes or changes due to ageing and were considered to be of no clinical significance. PMID- 1441144 TI - Prevalence, regional distribution and control of blowfly strike in England and Wales. AB - The prevalence and control of blowfly strike in England and Wales was investigated by a postal survey of 2451 sheep farmers, divided into five regions, who were asked about the blowfly seasons of 1988 and 1989. These were important years for the control of blowfly strike because the number of compulsory dips for the control of sheep scab was reduced from two to one in 1989. The response rate was 74.2 per cent. A larger proportion of farmers in the south west and south east reported strike (90 per cent), than in the north of England (60 per cent). The proportion of sheep with strike showed a similar regional variation (0.7 per cent in the north of England to 2.8 per cent in the south west). Dipping was the most common method of blowfly control, followed by tail amputation, dagging, spraying and cyromazine. Twenty per cent of farmers reported reducing the frequency of dipping in 1989, and of those 20 per cent increased the frequency of spraying and 20 per cent used cyromazine. PMID- 1441145 TI - Investigations into causes of death of endangered molluscs (Partula species). AB - Molluscs of the genus Partula are threatened with extinction; captive populations of some species have shown a marked and unexplained decline in numbers. Histopathological, electron microscopical and bacteriological studies were carried out on normal and 'pathological' specimens of Partula species. Although tissue changes and microorganisms were detected, the findings did not suggest that infectious or non-infectious disease contributed significantly to the disease or death of the snails. Additional investigations are suggested. PMID- 1441146 TI - Efficacy of moxidectin against gastrointestinal nematodes of cattle. AB - Three groups of 11 naturally infected crossbred beef calves were injected subcutaneously with moxidectin 1 per cent injectable at 0.2 or 0.3 mg moxidectin/kg bodyweight or with the unmedicated vehicle. Nematode infections had been acquired during grazing from December to April. Based on the faecal egg counts and total worm counts of the control calves at necropsy (11 to 13 days after treatment) most of the calves had heavy parasitic burdens. Ostertagia ostertagi was predominant and the mean numbers of adults, developing fourth stage larvae (L4) and inhibited early L4 were 45,906, 10,061 and 68,918, respectively. Haemonchus placei and Trichostrongylus axei were also present in the abomasa. Three species of Cooperia, Oesophagostomum radiatum L4 and T colubriformis adults were found in the intestinal tract. Both dosages of moxidectin were equally effective (P < 0.05) against all the abomasal nematodes (99.9 to 100 per cent) and the intestinal tract nematodes (99.4 to 100 per cent). No adverse reactions to the moxidectin treatment were observed. Abomasal pathology characteristic of heavy O ostertagi infection was observed in the control calves, but not in the treated calves. PMID- 1441147 TI - A thiamine responsive nervous disease in saltwater crocodiles (Crocodylus porosus). PMID- 1441148 TI - Laparoscopic salpingectomy in a hybrid flamingo. PMID- 1441149 TI - Docking of dogs. PMID- 1441150 TI - Effect of potassium on urinary acidosis. PMID- 1441151 TI - Idiopathic brainstem neuronal chromatolysis and hippocampal sclerosis: a novel encephalopathy in clinically suspect cases of bovine spongiform encephalopathy. AB - Some of the brains submitted for neurohistopathological examination under the Bovine Spongiform Encephalopathy (BSE) Orders did not show lesions of BSE. They showed neuronal chromatolysis and necrosis of the brainstem, perivascular cuffs and meningeal infiltrates of mononuclear cells and large irregularly shaped vacuoles in the neuropil. About half of them also showed loss of pyramidal neurons in the hippocampus, with astrocytic gliosis. The topography of the brainstem neuronal degeneration and vacuolation was the same in all the cattle, suggesting that neuronal necrosis and chromatolysis, vacuolation and hippocampal sclerosis are part of a spectrum of changes common to a single disease. The cows affected with such changes came from most parts of Scotland with the largest number from the north east. They were of various breeds, mostly suckler cows, and were aged from six to 16 years. Some cows had had no reported access to feed supplements. Clinically, the cows showed a range of neurological signs: tremor, ataxia, apprehension and weight loss were described in more than 80 per cent of the cases. The cause of the disorder was not determined. PMID- 1441152 TI - Observations on an outbreak of anthrax in pigs in north Wales. AB - Nineteen pigs in a 500 sow herd died from anthrax over a period of 95 days. This paper describes some of the problems encountered and how they were dealt with, including the risks to public health, the disposal of slurry and the cleansing and disinfection of the premises after the herd was slaughtered. PMID- 1441153 TI - Significance of the vaginal bacterial flora in the bitch: a review. AB - The literature on the bacterial flora in the vagina of the bitch is reviewed. The bacterial flora in the vagina of healthy bitches is compared with the flora of infertile bitches and bitches with vaginitis, and the role of Brucella canis as a cause of infertility is evaluated. Several investigators have recommended that bitches with reproductive disorders be treated with antibacterial drugs, but there is very little knowledge of the effect of this therapy on the bacterial flora in the vagina. PMID- 1441155 TI - Temporal relationship between progesterone and uterine lymphocyte-inhibitory activity in ewes. PMID- 1441154 TI - Isolation of Ehrlichia risticii from the aborted fetus of an infected mare. PMID- 1441156 TI - Optimum temperature of ovary transportation for in vitro fertilisation of bovine oocytes. PMID- 1441157 TI - Docking of dogs. PMID- 1441158 TI - Docking of dogs. PMID- 1441159 TI - Resistance to avermectins and milbemycins. PMID- 1441160 TI - Persistent Salmonella typhimurium PT 104 infection in a dairy herd. PMID- 1441161 TI - Isolation of Mycobacterium bovis from the respiratory tracts of skin test negative cattle. AB - Mycobacterium bovis was isolated from the respiratory tracts of three cattle which registered negative to tuberculin testing; no tuberculous lesions were found and the culture of lymph nodes and other tissues proved negative. One animal was from a group of five calves which had been inoculated intranasally with M bovis, and the organism was recovered once only from nasal mucus sampled 100 days after inoculation. The second animal had had contact with experimentally infected cattle which were excreting M bovis and the third was from a commercial farm. The results of ELISAS for antimycobacterial antibodies and interferon gamma, and of lymphocyte transformation assays are presented. The animals' immune responses provided evidence that each of them had been challenged. PMID- 1441162 TI - An outbreak of tuberculosis in pigs and cattle caused by Mycobacterium africanum. AB - An outbreak of tuberculosis in pigs and cattle caused by Mycobacterium africanum produced lesions in the pigs similar to those caused by M tuberculosis, M bovis and M avium, with caseation in the lymph nodes of the head and in the jejunal lymph nodes. Bacteriological examination of the dysgonic mycobacteria isolated showed that they were M africanum I. The intradermal tuberculin test was very reliable in pigs, differentiating between mammalian and avian reactions, and the results of the test were in accordance with the lesions found at meat inspection. No clinical signs were observed during the outbreak, and the infection was neither serious nor progressive. There were no lesions in the tuberculin-positive cattle. The source of the infection remains unknown. PMID- 1441163 TI - Possible effect of pH on the survival of leptospires in cattle urine. PMID- 1441164 TI - Pathogenicity of SAD rabies vaccine given orally in chacma baboons (Papio ursinus). PMID- 1441166 TI - Out-of-hours cover. PMID- 1441165 TI - Vectors of African horse sickness in the Cape Verde Islands. PMID- 1441167 TI - Bovine embryo transfer. PMID- 1441168 TI - Possible 'silo gas' poisoning in a bull. PMID- 1441169 TI - Injuries from air-guns. PMID- 1441170 TI - Data sheet correction. PMID- 1441171 TI - Economic progress. PMID- 1441172 TI - Hypomagnesaemia in a calf. PMID- 1441173 TI - Anaplastic sarcoma in the caudal thigh of a horse. AB - A 16-year-old showjumping gelding was examined because of a non-painful, slowly progressive caudal thigh swelling, which was associated with 2/10th lameness at the trot. Radiography, real time beta-mode ultrasonography and gamma-scintigraphy of the caudal thigh for the presence of chip fractures, sequestrum formation and, or, abscessation were inconclusive. Radiographic examination of the chest revealed multifocal, nodular cannon ball-like opacities throughout the entire lung fields from which a diagnosis of a primary soft tissue tumour with metastasis to the thorax was made. An anaplastic sarcoma was diagnosed port mortem in the candal thigh. At no time did the horse show signs of respiratory embarrassment. PMID- 1441174 TI - Prevalence of leg weakness in broiler chickens and its relationship with genotype. AB - A method for measuring the prevalence of leg weakness by assessing the walking ability of broilers was developed. Walking ability was divided into six categories, from completely normal to immobile. The method was found to give consistent results when performed by the same people. In a survey of commercial, intensively reared broilers, 90 per cent had a detectable gait abnormality and 26 per cent suffered an abnormality of sufficient severity for their welfare to be considered compromised. The prevalence of leg weakness in free range broilers, and three commercial breeds of broilers was determined. The results indicated that genetic factors were an important cause of leg weakness in broilers and also identified a possible relationship between liveweight and leg weakness. PMID- 1441175 TI - Time in lairage needed by pigs to recover from the stress of transport. AB - Two experiments were carried out in which a total of 602 pigs were slaughtered after being held in lairage for periods ranging from less than one hour to 21 hours. In the first experiment the pigs were handled under ideal conditions and slaughtered at the University of Bristol slaughterhouse; in the second the pigs were killed at a commercial plant. Blood samples collected at exsanguination were analysed for indices of stress. There were no consistent effects of time in lairage on the levels of lactate and creatine phosphokinase. Plasma cortisol and beta-endorphin levels were reduced by lairage for three hours or more in the first experiment and cortisol was reduced by lairage for two hours or more in the second; beta-endorphin was not measured in the second experiment. A period of rest in lairage allowed the pigs to recover from transport and the associated handling and the recovery appeared to be complete within two to three hours. PMID- 1441176 TI - Experimental infection of pregnant gilts with Leptospira interrogans serovar mozdok. AB - Three pregnant gilts were experimentally infected with leptospires of the serovar mozdok, isolated from an aborted pig fetus from a Portuguese pig farm with abortion problems. All the gilts aborted dead or dying piglets on days 105 or 106 of pregnancy. Serovar mozdok was isolated from 12 of the 22 piglets in the three litters. Histological examination of the livers and kidneys of the gilts at the end of the experiment revealed evidence of disease, and leptospires were isolated from their kidneys. Their serological responses up to 42 days after inoculation were monitored by means of a microscopic agglutination test, using 21 antigens from 18 serogroups. Cross reactions to heterologous antigens belonging to the Grippotyphosa, Australis, Icterohaemorrhagiae and Cynopteri groups were observed in all of them. PMID- 1441177 TI - Differential diagnosis of rinderpest and PPR using biotinylated cDNA probes. PMID- 1441178 TI - Firing of horses. PMID- 1441179 TI - Megabacteriosis in exhibition budgerigars. PMID- 1441180 TI - 'Mal seco' and grass sickness. PMID- 1441181 TI - Sudden death of calves by experimental infection with Strongyloides papillosus. II. Clinical observations and analysis of critical moments of the disease recorded on videotape. AB - Four calves experimentally infected with different doses of Strongyloides papillosus were examined for changes of body temperature and other clinical parameters. Also, the critical moments of death, which were recorded on videotape, were analyzed in detail. The first clinical signs included initial accelerated respiration. In general, body temperature was almost normal; however, one calf showed a slight increase after 2 or 3 days of infection, and two calves a gradual increase 7 days after infection. Vocal noises and general spasms were observed 5-14 times during the course of death. Initial vocal noises were heard between 0:50 and 1:30 (minute:second) after the appearance of the initial clinical signs. The final spasm, preceding death, occurred between 3:05 and 3:40 after the appearance of the initial clinical signs. PMID- 1441182 TI - Preventive treatment against toxocarosis in bovine calves. AB - Treatment of bovine calves 10-16 days old with an anthelmintic which is effective against immature Toxocara vitulorum killed the parasites, there was no new infection and recontamination of the environment was precluded. When the management of the program was delegated to the livestock officers, approximately 3% of calves scheduled for treatment developed patent infections. The prevalences of toxocarosis on the different farms were correlated with annual rainfall, probably because the longer dry periods associated with lower rainfall killed infective eggs in the environment. The treatment schedules prevailing before the study commenced were ineffective. The prevalence of toxocarosis in the bovine calves on farms in the area with an annual rainfall of about 1000 mm was lower than that in buffalo calves studied previously in the same area. PMID- 1441183 TI - Sex-related susceptibility of bulls to gastrointestinal parasites. AB - The effects of sex and anabolic implants on fecal egg counts and pasture contamination were examined in 77 naturally infected yearling bulls, steers, and heifers of mixed beef breeds grazing the same contaminated pasture in southern Ohio in the spring of 1990. Fecal egg counts were compared in seven groups of 10 14 animals each, twice before anabolic implants and twice after implants. Comparisons were made between untreated bulls, steers, and heifers, between steers with and without implants, and between heifers with and without implants. Bulls had significantly (P < 0.01) higher fecal egg counts than steers, and counts from steers were not significantly different to those from heifers. There were no significant differences between counts from implanted and control steers or heifers. The results have important practical implications both for parasite control and for bovine parasite research. There is a need to pay special attention to young bulls when designing parasite control programs, and to distribute the sexes equally between groups when doing research trials with cattle of mixed sexes. Some previous studies on worm population dynamics and anthelmintic evaluation may need to be re-examined in the light of sex differences. PMID- 1441184 TI - The development of naturally acquired cyathostome infection in ponies. AB - Groups of animals of different ages and experience of previous parasite exposure were allowed to graze a single pasture for 5 weeks in autumn (7 October to 11 November). There was evidence that previous exposure modified cyathostome development, as acquired burdens in foals which had previously grazed were smaller and developed more slowly than those of helminth-naive animals of the same age. The burdens acquired by yearling and adult ponies were of a similar size to those of the previously grazed foals, but the incidence of arrested development was higher in the younger groups of foals and yearlings when compared with adults. Further evidence of an effect of age on cyathostome development was that the level of faecal egg output of the adult ponies was lower than in the groups of young animals. PMID- 1441185 TI - Immunological and feeding studies on antigens derived from the biting fly, Stomoxys calcitrans. AB - Pairs of rabbits were immunised with three antigenic preparations derived from Stomoxys calcitrans gut, abdominal section and whole flies. Immunoblotting studies demonstrated that a humoral response was mounted against eight antigens from the gut preparation and 12 each from the abdominal and whole fly preparations. In vitro feeding experiments showed higher mortality between Days 4 and 7 in the group of flies which had fed upon blood from rabbits inoculated with the gut derived antigen. This group also produced the lowest percentage of viable eggs (15.5%). PMID- 1441186 TI - Leishmaniasis in Mediterranean countries. AB - The epidemiology of visceral and cutaneous leishmaniasis is described in the Mediterranean countries where a recrudescence and a geographical spread of these zoonoses are noted. Recent findings concerning isoenzyme identification of the causative agents are given and the problems encountered in the development of vaccines to protect humans and dogs are discussed. PMID- 1441187 TI - Cellular immune responses in the skin of sheep infected with larvae of Lucilia cuprina, the sheep blowfly. AB - Cellular immune responses were observed in the skin of sheep after primary and secondary infection with sheep blowfly (Lucilia cuprina) larvae. Both primary and secondary infections resulted in a massive cellular infiltration within 48 h of wound initiation, with the majority of cells having the CD45 phenotype. Neutrophils comprised the major cell type at the skin surface. In the dermis, the number of CD4+ T helper, gamma delta-TCR+ cells and T19+ (CD4-, CD8-) T cells also increased significantly in skin during both primary and secondary infections compared with control sites. However, there was no significant difference in the numbers of these cells between primary and secondary infections. An increase in the expression of the CD1 antigen on Langerhans/dendritic cells was observed, along with an apparent increase in the number of these cells in secondary lesions, with the majority of the cells being concentrated in the upper dermis and epidermis. While there was no increase in mast cells, eosinophils increased significantly during infection compared with control sites. The cellular infiltration observed following primary and secondary infections suggests polyclonal activation of T cells and their selective recruitment to the lesion site. PMID- 1441188 TI - Arthropoda as zoonoses and their implications. AB - Some aspects of changing patterns of arthropodal infections and arthropod-borne diseases in Mediterranean areas are briefly discussed. Selected examples are given, with particular emphasis on the phenomenon of the synanthropic flea Ctenocephalides felis felis and on health problems caused by human infections with Argas reflexus, the common tick of urban pigeons in Europe. Finally, the risk of the emergence of Lyme borreliosis (Borrelia burgdorferi) is considered in relation to the increasing spread of environmental infestation with ticks, mainly Ixodes ricinus, an efficacious vector for the spirochaete. PMID- 1441190 TI - World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) methods for the detection of anthelmintic resistance in nematodes of veterinary importance. AB - Methods have been described to assist in the detection of anthelmintic resistance in strongylid nematodes of ruminants, horses and pigs. Two tests are recommended, an in vivo test, the faecal egg count reduction test for use in infected animals, and an in vitro test, the egg hatch test for detection of benzimidazole resistance in nematodes that hatch shortly after embryonation. Anaerobic storage for submission of faecal samples from the field for use in the in vitro test is of value and the procedure is described. The tests should enable comparable data to be obtained in surveys in all parts of the world. PMID- 1441189 TI - The development of a recombinant Babesia vaccine. AB - Crude extracts of Babesia bovis parasites were shown to induce levels of protection in susceptible cattle equivalent to that resulting from natural infection. The crude material was systematically fractionated and tested in numerous sequential vaccination/challenge experiments in adult cattle. Antigens in protective fractions were then purified by affinity chromatography with monoclonal antibodies. Three highly protective (more than 95% reduction in parasitaemias) antigens were thus identified. None of these antigens was immunodominant; a number of immunodominant antigens were identified and all were immunosuppressive and/or non-protective. The three protective antigens were cloned and expressed as either beta-galactosidase or glutathione-S-transferase (GST) fusion proteins. Two of these, GST-12D3 and GST-11C5, when used in combination were almost as protective as has been previously shown for the commercially available live attenuated vaccine. A short fragment of a third antigen (21B4) has also been shown to be protective. In two of the antigens, repetitive segments have been shown to be non-protective while the third antigen (12D3) does not contain repetitive domains. Homologues of these antigens exist in other Babesia species and it is anticipated that these may be candidate antigens for protective vaccines against those species. PMID- 1441191 TI - Some glucose metabolic enzymes in various fractions of sarcocysts of Sarcocystis fusiformis of buffalo (Bubalus bubalis). AB - A comparative biochemical study on some enzymes of glycogenolysis, glycolysis and the hexose monophosphate shunt pathway in various fractions (cyst wall, cyst fluid and zoites) of the sarcocysts of Sarcocystis fusiformis from the oesophageal muscles of naturally infected Indian water buffalo (Bubalus bubalis) was carried out. The pattern and the magnitude of enzymic activity differed markedly in these fractions. Phosphorylase, hexokinase, aldolase and pyruvate kinase showed their highest levels of activity in the zoites fractions, whereas lactate dehydrogenase was the highest in cyst fluid. Alcohol dehydrogenases were non-detectable. Glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were localized in the cyst wall only. Zoites were considered to be the most active metabolic sites for glucose breakdown. PMID- 1441192 TI - The epidemiology of tropical theileriosis (Theileria annulata infection in cattle) in an endemic area of Morocco. AB - A longitudinal study of tropical theileriosis was performed on 12 farms in the Doukkala region of Morocco during 1990. Adult Hyalomma detritum detritum were collected between March and early October and a peak in numbers was observed at the end of June. Nineteen percent (24/127) were infected with Theileria species and, amongst these, over 50% had five or more sporoblasts in their salivary glands (range 1-151). Hyalomma d detritum larvae and nymphs were found on cattle between September and early December with the highest numbers in late October. The prevalence of T. annulata piroplasm carriers at the beginning of the year was 48.5% (47 positive out of 97) and there were 14 new infections during the disease season (March to September) of which five developed into clinical cases. The incidence rates of new infection and clinical disease were 0.156 and 0.056 per animal-season, respectively. Differences were observed between age categories of cattle in both tick and parasite infections. A significantly lower number of adult H.d. detritum were collected from calves than from adult cattle. The prevalences of piroplasm carriers before the disease season were 0%, 36% and 76%, respectively, in (a) calves which had been born since the previous disease season, (b) calves born before then and (c) adults. However, the incidence rates of infection and disease for uninfected animals in the two categories of calves were approximately the same: 0.299 and 0.378 new infections, and 0.085 and 0.126 clinical cases per animal-season for (a) and (b), respectively. The date predicted for the appearance of adult H.d. detritum, based on published tick development times and local temperature records, was within 2 weeks of the study visit when the highest number of adults were collected from cattle. However, the date predicted for the appearance of larvae was 6 weeks earlier than the observed peak populations and may indicate that H.d. detritum delays either egg laying in the summer or larval host searching in the autumn. PMID- 1441193 TI - Frequency distribution of Echinococcus granulosus hydatid cysts in sheep populations in the Xinjiang Uygur Autonomous Region, China. AB - Age-prevalence and age-intensity data of Echinococcus granulosus hydatid cysts in sheep populations were collected in an abattoir in the Xinjiang Uygur Autonomous Region, People's Republic of China. The frequency distribution of the larval cysts per sheep was empirically described by the negative binomial model, with parameter k being 0.5273. A mathematical model for the life cycle of E. granulosus was applied to the collected data and the results show that the infection pressure on sheep was 0.4362 (female) or 0.4119 (male) infections per year, the mean number of cysts increased linearly by 0.8824 (female) or 0.9971 (male) cysts every year and acquired immunity was too low to depress this rate of increase. According to certain definitions of steady states for taeniid populations, it was concluded that at least in some parts of Xinjiang, the life cycle of E. granulosus was and may still be in an endemic steady state. Consequently, the regular dog-dosing program would readily drive the infection from an endemic state towards extinction. PMID- 1441194 TI - Isoenzyme analysis of Haemonchus contortus resistant or susceptible to ivermectin. AB - Three different strains of Haemonchus contortus (susceptible to ivermectin, S IVM; selected for resistance to ivermectin, R-IVM; a multiple resistant strain, i.e. resistant to benzimidazole and ivermectin, R-IVM/SA) were examined for isoenzyme variation by starch gel electrophoresis. Using stains for seven enzymes separated in five different buffer systems, no differences in the electrophoretic mobility could be detected between any of the strains. Results demonstrate a low level of enzyme variation in H. contortus and no differences in enzyme electrophoretic profile between IVM-sensitive and IVM-resistant parasites. Differences between the ivermectin-sensitive and both ivermectin-resistant strains were observed with the propionyl esterases and although some of the differences are probably associated with benzimidazole resistance, others are associated with resistance to ivermectin. The three strains of H. contortus are generally identical; however, differences between all strains of H. contortus and a strain of Dictyocaulus viviparus were detected. PMID- 1441195 TI - Efficacy of the morantel sustained release trilaminate bolus against gastrointestinal nematodes and its influence on immunity in calves. AB - An experiment was conducted in calves to investigate the efficacy of a morantel sustained release trilaminate bolus (MSRT) to control gastrointestinal parasitism and to assess the development of immunity during the use of MSRT. Two groups (M and U) of four calves each were infected three times a week with a mixed Ostertagia ostertagi and Cooperia oncophora infection for 12 weeks. Calves of Group M received an MSRT at the start of the experiment. Twenty weeks after the start of the experiment, all animals, including a previously uninfected control group (C), received a challenge with 100,000 Ostertagia and 100,000 Cooperia. After a further 4 weeks all calves were necropsied for worm counts. During the trial calves were weighed and faecal egg counts, larval differentiation and pepsinogen concentrations were determined. The results demonstrated the high level of efficacy of the MSRT in reducing the faecal egg output and preventing parasitic gastroenteritis under conditions of a continuous high rate of infection. Efficacy of treatment was higher for Cooperia than for Ostertagia. Post-mortem worm counts suggested a partially impaired immunity build-up in Group M, at least for Cooperia. PMID- 1441196 TI - An ELISA for detection of antibodies against porcine epidemic diarrhoea virus (PEDV) based on the specific solubility of the viral surface glycoprotein. AB - Viral proteins of porcine epidemic diarrhoea virus (PEDV) were extracted from the cytoplasm of infected Vero cells using hypotonic conditions and a non-ionic detergent. Both the pH and the NaCl concentration of the extraction buffer were varied in attempts to increase the solubility of the virion spike glycoproteins (S-protein) and of the nucleocapsid proteins (N-protein). Monoclonal antibodies, hyperimmune sera and convalescent pig sera were used to identify and monitor these proteins by immunoprecipitation and Western blots. The solubility of the S protein was optimal at pH 4, whereas that of the N-protein was optimal at pH 9. Consequently, it was possible to enrich for either S-protein or N-protein; increases in the NaCl concentration of the buffer were of no advantage in this respect. Enriched preparations of the S-protein and N-protein were used as ELISA antigen for the S-ELISA and N-ELISA, respectively. The S-ELISA proved to be the more effective of the two immunoassays. Antibodies against S-protein remained detectable for longer periods of time than anti-N-protein antibodies in the sera of PEDV-infected pigs. Using this ELISA of increased sensitivity, it was observed that only a small number of farms in Switzerland had been infected with PEDV. PMID- 1441197 TI - Serological characterization of Actinobacillus pleuropneumoniae strains isolated from pigs in Quebec. AB - A total of 3306 isolates of A. pleuropneumoniae originating from lung tissues of pigs that died of acute pleuropneumonia and 140 isolates recovered from tonsils or nasal cavities of apparently healthy pigs from chronically infected herds were serotyped. Various serotyping methods, such as slide agglutination, tube agglutination, ring precipitation, coagglutination, immunodiffusion, indirect hemagglutination and counterimmunoelectrophoresis either alone or in combination were used. The techniques used for serotyping continued to evolve during the last 10 years depending on the problem encountered in serotyping. Antisera prepared in rabbits against formalinized whole cell suspensions of reference strains of A. pleuropneumoniae of serotypes 1 to 12 were employed for serotyping. Serotype 1 was predominant ranging from 55 to 87% from year to year during the last 10 years with an average prevalence of 68%. Serotype 5 was second in prevalence ranging from 9 to 30% with a mean of 23%. Both subtypes of serotype 5 (5a and 5b) were present in Quebec. Serotypes 3, 6, 7, 8, 10 and 12 were isolated in small numbers together accounting for about 9%. Serotypes 4, 9 and 11 were not present. Cross reactions were observed among isolates of serotypes 3, 6 and 8, and 1, 9 and 11 and were easily differentiated from each other by quantitation of type and group specific antigens by coagglutination and immunodiffusion tests. Serotypes 1, 5 and 7 were isolated most frequently from tonsils of pigs from chronically infected herds. Prevalence of different serotypes in different countries has also been reviewed. PMID- 1441198 TI - Diphenylamine increases cloacin DF13 sensitivity in avian septicemic strains of Escherichia coli. AB - Thirteen avian septicemic isolates of Escherichia coli were examined for the presence of the aerobactin iron transport system. All of the strains possessed a functional aerobactin system and hybridization experiments showed that the aerobactin genes were located on ColV-type plasmids in all cases. The expression of the aerobactin receptor IutA was also studied by determining the bacterial susceptibility to the bacteriocin cloacin DF13. Twelve of the 13 isolates were cloacin-resistant but became sensitive to this bacteriocin upon treatment with diphenylamine which caused a reduction in the amount of O-side chain lipopolysaccharide. PMID- 1441199 TI - Development of a species-specific DNA probe for Mycoplasma capricolum. AB - A specific DNA probe for the detection and identification of Mycoplasma capricolum, one of the causative agents of contagious agalactia syndrome, was selected from a genomic library. It consists of a 900bp RsaI genomic fragment of M. capricolum (reference strain), cloned into the EcoRV site of the plasmid Bluescript. By using the appropriate stringency this radiolabelled probe reacts specifically with M. capricolum when tested by dot blot hybridization against various mycoplasmal DNAs. The current level of sensitivity of the 32P-labelled 900bp RsaI probe is 500 pg of homologous DNA, corresponding to 5 x 10(4) mycoplasmas. A non radioactive labelling method, using the digoxigenin-11-dUTP, was also tested. The specificity of the digoxigenin-labelled probe was equivalent to that obtained with the radioactive probe. However the sensitivity of detection decreased to 1 ng of homologous DNA detected, corresponding to 1 x 10(5) mycoplasmas. Tests performed with milk samples have demonstrated that the radioactive 900 bp RsaI probe indeed detected M. capricolum contained in milk. A positive signal was obtained when 10(5) M. capricolum were present in the spot. PMID- 1441200 TI - [Potentialities of x-ray diagnosis in improving the diagnosis of oncologic diseases in outpatient clinics]. AB - The authors analyze the possibilities of improving the prehospital diagnosis of the most prevalent oncologic diseases (tumors of the lungs, stomach, large intestine, mammary gland) that may be effectively detected by modified methods of x-ray and x-ray fluorographic examinations. The x-ray diagnostic service of health centers is regarded as a most important component in the system of prehospital diagnosis. A program of reorganization of this service is suggested, that will help reorient its activities to purposeful screening examinations that will altogether improve the detection of a number of oncologic diseases. PMID- 1441201 TI - [Use of DIL-type cava filters for the prevention of thromboembolism of the pulmonary artery]. AB - New type cava filters were employed to prevent pulmonary artery thromboembolism in 12 cases. DIL cava filter was used, that represents a string made of a special alloy that can 'memorize' its shape. The design of this filter is in principle different from all the known filters, for it functions as an intraluminal filter and at the same time stretches the vena cava inferior, enlarging its diameter in the frontal plane. The DIL cava filter proved to be effective in the majority of cases, but if the walls of vena cava inferior were too rigid, for example, if a tumor grew into them, it was difficult to place the filter properly. On the whole this filter is characterized by a number of advantages: it can be easily implanted via 7 F catheter without injuring the vena cava inferior walls. No cases of dislocation of cava filters in relation to bone markers were noted in 9 patients over 60 +/- 17 days. PMID- 1441202 TI - [X-ray and ultrasonic diagnosis of noninflammatory benign diseases of the gallbladder]. AB - The author analyzes the results of x-ray (cholecystography) and ultrasonic examinations carried out in patients with noninflammatory benign diseases of the gallbladder (71 with cholesterosis and 28 with adenomyomatosis). X-ray and ultrasonic symptoms of these conditions are presented and the diagnostic potentialities of both methods in the detection of such diseases assessed. The author considers ultrasonic scanning the method of choice for the diagnosis of any forms of gallbladder cholesterosis, whereas an x-ray examination appears to be informative only in a polypous form of the disease. X-ray contrast examination is preferable for the recognition of gallbladder adenomyomatosis, for it presents a clear-cut pattern characteristic of each form of this condition, whereas ultrasonic symptoms of such involvement are nonspecific. PMID- 1441203 TI - [A complex x-ray endoscopic study in complicated cholelithiasis]. AB - Recurrent or residual choledocholithiasis was diagnosed in 202 patients with a history of cholecystectomy, in 148 cases this condition was combined with papillostenosis. Transfistula extraction of the concrements and endoscopic papillosphyncterotomy helped achieve cure of 186 (92%) patients without relaparotomy. The authors discuss the role of roentgenology in such combined x ray and endoscopic diapedetic examinations and emphasize its role in identification of the diagnostic details that are so important for the choice of the optimal treatment strategy. They come to a conclusion that the results of treatment of complicated cholelithiasis by 'minor surgery' means depend not only on the manipulations and skills of the surgeon endoscopist, but on the full-value employment of roentgenology as well. PMID- 1441204 TI - [A standardized x-ray examination in the diagnosis of tumors of the large intestine]. AB - High morbidity and mortality rates because of large intestinal carcinoma and a clear-cut tendency to the growth of these rates have prompted the authors to undertake this study. When new methods of radiodiagnosis appeared, traditional and highly informative methods, Ba enema among them, seemed to be forgotten. The authors suggest a program of standard examinations of the large intestine, based on simultaneous double-contrast technique, that permits an essential improvement of the diagnostic and economic efficacy of this one of the most prevalent methods of x-ray examinations. The suggested technique was used in examinations of 4120 patients with suspected tumors of the large intestine. PMID- 1441205 TI - [Radiodiagnosis of kidney diseases in a municipal hospital]. AB - Ultrasonic (US) examinations of the urinary tract of 2384 patients have revealed pathologic shifts in 725 cases; x-ray examinations had to be carried out in 632 of these to specify the diagnosis. X-Ray and US-based radiodiagnosis of a wide spectrum of renal diseases, carried out at a common municipal hospital, promotes a better diagnosis. Employment of US examinations as a screening method helps recognize renal hypoplasia, cystic diseases, and an acute inflammatory process, renal carbuncle, fairly well. The diagnosis of other renal abnormalities, urolithiasis, hydronephrotic transformations, tumors and injuries still has to be specified by routine x-ray methods. PMID- 1441206 TI - [Computed tomography in the diagnosis of stomach cancer and the assessment of its spread]. AB - CAT was carried out in 110 patients with gastric carcinoma and its findings compared with the intraoperative findings. CAT involved a polypositional scanning (depending on the tumor site) against the background of oral contrast label of the stomach and intestine. CAT potentialities in the diagnosis of gastric carcinoma, assessment of the tumor size and involvement of the adjacent organs and structures, detection of the metastases were studied. Use of CAT in complex with other methods will help choose the optimal treatment strategy and determine the volume of supposed surgical intervention. PMID- 1441207 TI - [The role of x-ray computed tomography in the topical diagnosis of insulinomas of the pancreatic gland]. AB - Pancreatic insulinomas were intraoperatively revealed in 15 patients. X-ray computed tomography (CAT) revealed the tumor in only 6 (40 %) patients. The mean size of detectable insulinomas was 2.4 cm, that of undetectable ones 1.2 cm. X ray CAT diagnosis is facilitated in case of a superficial localization of the tumor on the body or tail of the gland . PMID- 1441208 TI - [Radiodiagnosis of adrenal gland diseases]. PMID- 1441209 TI - [Improvement of x-ray diagnosis in stomatology]. PMID- 1441210 TI - [Ultrasonic diagnosis of non-Hodgkin's lymphoma]. AB - Analyzes the results of ultrasonic examinations of 111 patients with various forms of non-Hodgkin's lymphomas. Reviews ultrasonic semeiotics of non-Hodgkin's lymphadenopathy of the abdominal cavity and retroperitoneal space and of extranodal variants of lymphoma course (with involvement of the spleen and stomach). Suggests the most safe method for precision diagnostic aspiration biopsy of the spleen monitored by ultrasound. The author considers ultrasonic examination to be a valuable method for the diagnosis of non-Hodgkin's lymphomas; it is economic, rapid, safe, permits a simultaneous assessment of the status of many organs and systems. The results of ultrasonic examinations should be assessed in complex with the results of other diagnostic methods. Ultrasonic examination should be considered as a method of choice for monitoring patients with diagnosed non-Hodgkin's lymphoma. PMID- 1441211 TI - [Radiologic methods in the diagnosis of diseases of the spleen]. AB - Ultrasonic and computer-aided tomographic examinations of 2457 patients with suspected diseases of the abdominal cavity organs have revealed splenic involvement in 48. The sensitivity of ultrasonic technique for the detection of splenic diseases has made up 70.8%, that of computer-aided tomography--95.8%. Invasive interventions monitored by these two methods were carried out in 26 patients; in 10 of these transcutaneous puncture drainage was carried out for cysts (2), hematoma (1), and abscesses of the spleen (7). In one patient with multiple abscesses of the spleen the drainage was found insufficient for complete cure and he had to be subjected to splenectomy, in the rest cases surgery did not have to be resorted to. Therefore, ultrasonic and computer-aided tomographic examinations of the spleen, used together with various invasive interventions, result not only in correct diagnosis and differential diagnosis of this organ's disease, but permit various therapeutic measures and help achieve cure without laparotomy. PMID- 1441213 TI - [The frequency of recurrences and metastases of bladder cancer following a radical course of radiotherapy]. AB - The authors compare the incidence of bladder carcinoma recurrences and dissemination after long-distance gamma-beam therapy, carried out according to a traditional method, and in an accelerated hyperfractionation mode combined with metronidazole therapy. The recurrences were most frequently detected at the site of the primary tumor (62-67% of cases) in 6 to 18 months after the treatment. They come to a conclusion that accelerated hyperfractionation and local metronidazole radio-modification were conducive to a reduction of the incidence of recurrences from 45 to 28% as against the traditional split radiotherapy course in the classical fractionation mode. PMID- 1441212 TI - [The differential diagnosis of an abdominal aortic aneurysm and a retroperitoneal para-aortal hematoma]. PMID- 1441214 TI - [Comprehensive clinical and x-ray diagnosis of shock lung in children and adults]. PMID- 1441215 TI - [Cancer of the stomach--new and "old" problems of diagnosis]. AB - The author discusses present-day potentialities of radiodiagnosis of gastric carcinoma. Analysis of more than 2000 case histories brings him to a conclusion that the problem of the detection of this condition is particularly intricate for two reasons: the absence of active screening for gastric carcinoma in high-risk groups and inadequate attention to its endophytic forms. The author's data evidence that intramural growth of gastric carcinoma is responsible for up to 75% of all its anatomic forms. So high an incidence of endophytic carcinomas of the stomach necessitates a combination of the x-ray and endoscopic methods in gastro oncology. Making use of the total scope of present-day diagnostic methods, including routine techniques, double-contrast examination, and, in recent years, x-ray computer-aided tomography and ultrasonic examinations, the author gives recommendations that will help solve quite a number of problems in radiodiagnosis of gastric carcinoma. PMID- 1441216 TI - The potential of molecular biology for the production of monoclonal antibodies derived from outbred veterinary animals. AB - The protein structure of immunoglobulins and the genetics on the regulation of immunoglobulin expression are reviewed. This basic knowledge has led to the development of systems to produce monoclonal antibodies in eukaryotic or prokaryotic cells. The potential and limitations of molecular biology for the understanding of immunoglobulin regulation and for the production of monoclonal antibodies derived from animals of veterinary importance are discussed. PMID- 1441217 TI - Bovine major histocompatibility complex class I specific monoclonal antibodies characterized by flow cytometry, one- and two-dimensional electrophoresis, western blot and inhibition of cytotoxic T lymphocyte function. AB - To identify and characterize the bovine major histocompatibility complex (MHC) class I molecules, a panel of 11 monoclonal antibodies (mAbs) were analyzed. The mAbs reacted with bovine MHC class I antigens, as assessed by flow cytometry and immunoprecipitation followed by one- and two-dimensional gel electrophoresis. Analysis by flow cytometry revealed that class I molecules were expressed less on a class I mutant B-lymphoblastoid cell line than on the parent cell line. The relative molecular weights of the proteins identified by these mAbs were similar to those reported previously for cattle and humans. Nonequilibrium pH gradient two-dimensional gel electrophoresis showed that RH16C recognized four different class I gene products, indicating this mAb reacts with a conserved epitope present on different class I molecules. These mAbs effectively blocked cytotoxic T lymphocyte killing of allogeneic lymphoblasts, suggesting the functional importance of beta-2m in this process. These mAbs should be useful reagents for studying bovine MHC class I molecules. PMID- 1441218 TI - Sheep macrophages express at least two distinct receptors for IgG which have similar affinity for homologous IgG1 and IgG2. AB - Ovine bone marrow-derived macrophages (BMM) may express several IgG receptor (Fc gamma receptor; FcR) subsets. To study this, model particles (opsonized erythrocytes; EA), which are selectively handled by certain FcR subsets of human macrophages were used in cross-inhibition studies and found to react in a similar manner with FcR subsets of sheep macrophages. In experiments with monoclonal antibodies against subsets of human FcR, human erythrocytes (E) treated with human anti-D-IgG (anti-D-EAhu) and sheep E treated with bovine IgG1 (Bo1-EAs) were handled selectively by human macrophage FcRI and FcRII, respectively. Rabbit IgG-coated sheep E (Rb-EAs) were recognized by FcRI, FcRII and possibly also by FcRIII of human macrophages. Anti-D-EAhu, Bo1-EAs and Rb-EAs were also ingested by sheep BMM. Competitive inhibition tests, using various homologous and heterologous IgG isotypes as fluid phase inhibitors and the particles used as FcR specific tools in man (anti-D-EAhu and Bo1-EAs), revealed a heterogeneity of FcR also in sheep BMM. Thus, ingestion of anti-D-EAhu by ovine BMM was inhibited by low concentrations of competitor IgG from rabbit or man in the fluid phase, but not at all by bovine IgG1, whereas ingestion of Bo1-EAs was inhibited by bovine IgG1. This suggested that anti-D-EAhu were recognized by a FcR subset distinct from that recognizing bovine-IgG1. It was concluded that sheep BMM express functional analogs of human macrophage FcRI and FcRII and that Bo1-EAs and anti-D EAhu are handled by distinct subsets of BMM FcR. All EAhu tested (EAhu treated with anti-D, sheep IgG1 or sheep IgG2) were ingested to a lower degree than EAs. This inefficient phagocytosis could be enhanced by treatment of EAhu with antiglobulin from the rabbit, suggesting that it is caused by a low degree of activity of opsonizing antibodies rather than special properties of the erythrocytes themselves. Several lines of evidence suggested that both FcR subsets of ovine BMM recognize both ovine IgG1 and IgG2. In contrast, bovine IgG1 reacts with one FcR subset and bovine IgG2 interacts inefficiently with all FcR of ovine BMM. PMID- 1441219 TI - Development and persistence of Cowdria ruminantium specific antibodies following experimental infection of cattle, as detected by the indirect fluorescent antibody test. AB - Different breeds of cattle were experimentally infected with Palm River, a Zimbabwean isolate, or Ball-3, a South African isolate of Cowdria ruminantium, derived from tissue culture or tick or blood stabilates. C. ruminantium specific antibody responses were detected by an indirect fluorescent antibody test (IFAT) using C. ruminantium-infected bovine aortic endothelial (BAE) cell cultures as antigen. The first detection of antibodies to C. ruminantium generally coincided with the peak of the febrile reaction and the antibodies remained detectable for a period of 8-30 weeks in the Palm River infected group and 18-30 weeks in the Ball-3 infected group. Peak reciprocal antibody titres in both groups ranged from 64 to 2048 between 3 and 6 weeks post-infection. No apparent serological differences were observed among the various C. ruminantium isolates when tested in homologous and heterologous IFATs. Post-infection sera to Anaplasma marginale, Theileria parva parva, Babesia bigemina and Rickettsia conorii did not exhibit reactivity with the C. ruminantium antigen. These results indicate the possible use of C. ruminantium-infected cultures as antigen in IFATs to detect similar C. ruminantium-specific antibody responses in the field in clinically sick, recovered and carrier animals. PMID- 1441220 TI - Bovine haptoglobin: single radial immunodiffusion assay of its polymeric forms and dramatic rise in acute-phase sera. AB - Using purified bovine haptoglobin (Hp) and specific antisera, a single radial immunodiffusion (SRID) assay method has been developed to measure the serum Hp level in cattle. Bovine Hp is a highly polymerized protein showing heterogeneous molecular forms in serum. After treatment with cysteine or glutathione, Hp was partially reduced to a homogeneous form, suitable for SRID assay. This method gives values comparable to those obtained by hemoglobin-binding capacity assay, and has the advantage of being simple and convenient. Although serum Hp was not detectable in healthy cattle, it was found more than 50-fold after invasive surgery, indicating that Hp is a characteristic acute-phase protein in cattle. PMID- 1441221 TI - Autoimmune haemolysis in the dog: relationship between anaemia and the levels of red blood cell bound immunoglobulins and complement measured by an enzyme-linked antiglobulin test. AB - A direct enzyme-linked antiglobulin test (DELAT) was used to measure the levels of red blood cell (RBC) bound IgG, IgM, IgA and C3 in dogs with autoimmune haemolytic anaemia (AIHA). At presentation, one or more DELAT parameters was raised in each AIHA case, and the RBC were typically coated with immunoglobulin of more than one class, together with C3. There was no relationship between the levels of RBC-bound IgG, IgM or IgA and the severity of the anaemia, although a significant negative correlation (rs = -0.66, P < 0.02) was found between bound C3 and blood haemoglobin concentration. These results indicate that the level of sensitisation of erythrocytes with IgG alone is not a reliable predictor of the severity of haemolysis in different cases, and that the pathogenesis of AIHA can be complex, involving multiple immunoglobulin classes and complement in the destruction of RBC. A significant relationship (rs = 0.63, P < 0.02) was found between serum IgG concentration and haemoglobin levels, and it is suggested that this may be due to free IgG inhibiting the interaction of IgG-sensitised RBC with macrophages. Serial measurements from individual AIHA cases during treatment revealed that the levels of RBC-bound immunoglobulins fell simultaneously with improvements in anaemia. In one dog, a relapse was associated with increases in bound IgG and IgM. Transient relative reticulocytopenia at presentation was common, but was not related to the severity of the anaemia. However, in other cases there was a persistent failure to increase RBC production, which was associated with slower recovery. PMID- 1441222 TI - Identification and characterization of rat intestinal lamina propria cells: consequences of microbial colonization. AB - Germ-free (GF) animals exhibit an abnormally diminished, cell-mediated immune response which can be rapidly normalized by bacterial colonization of the intestine. This conventionalization suggests that the development and/or regulation of the immune system is dependent upon intestinal bacteria or their products. Here we consider the ontogeny of gut-associated lymphoid tissue (GALT) immunocytes by isolating and characterizing the intestinal lamina propria cells (LPC) of GF rats responding to bacterial colonization or an irrelevant protein antigen, and compared to LPC of specific pathogen-free (SPF) rats which were conventionalized (CV) from birth. Isolation of cells was accomplished by successive EDTA washings of small intestine to remove the epithelium, and enzymatic digestion of the tissue generating single-cell suspensions. Resulting cell suspensions were characterized by monoclonal antibodies directed against leukocyte epitopes using flow cytometry. Functional characterization was measured by the tritiated thymidine proliferation assay with concanavalin A (Con A) and lipopolysaccharide (LPS) as co-stimulators. Germ-free and SPF rats had fewer total LPC than CV rats. Antibody staining revealed that GF rats had fewer total leukocytes than CV and SPF rats, and that CV rats had a greater percentage of T cells and cells positive for the C3 receptor than GF rats. Co-stimulation of LPC with mitogens only increased proliferation of cells from CV rats compared to GF and SPF rats. In addition, spleen cells from CV rats demonstrated significantly enhanced proliferative responses compared to spleen cells from GF rat and were more analogous to spleen cells from SPF rats in their ability to proliferate in vitro, with and without mitogens. We conclude that T-cells and CD35-positive (C3BR+) cells are recruited and/or proliferate in response to intestinal bacteria and/or their products, and that this results in the induction of immune competency. PMID- 1441223 TI - Detection of IgM rheumatoid factor in canine serum using a standardized enzyme linked immunosorbent assay. AB - An ELISA measuring IgM rheumatoid factor (RF) in dog serum is presented. Dog sera and a human IgM RF standard, calibrated against the international World Health Organisation (WHO) standard, are compared. It is concluded that the human IgM RF standard may be used as reference serum in the canine assay, which makes it possible to compare results from different veterinary laboratories. PMID- 1441224 TI - Effect of aflatoxin B1 on in vitro production of interleukin-1 by bovine mononuclear phagocytes. AB - In this study we examined the effects of preincubation with aflatoxin B1 (AFB1) on the ability of bovine monocytes to produce the immunological mediator interleukin-1 (IL-1). Monocytes preincubated for 6-24 h with 10 micrograms ml-1 AFB1 demonstrated a diminished capacity to release IL-1 activity in response to bacterial lipopolysaccharide (LPS). Preincubation for less time, or with lower concentrations of AFB1, did not affect IL-1 release. Pretreatment of monocytes with AFB1 also resulted in diminished release of IL-1 activity in response to in vitro infection with Listeria monocytogenes. Incubation with AFB1 reduced the amount of IL-1 beta mRNA in LPS-stimulated bovine monocytes; however, this was observed only at high concentrations of AFB1 that non-specifically reduced steady state transcription of actin mRNA. We therefore concluded that AFB1 does not specifically suppress monocyte release of IL-1, other than through its general inhibition of mRNA transcription. PMID- 1441225 TI - Immunological parameters in meat-type chicken lines divergently selected by antibody response to Escherichia coli vaccination. AB - Our group has established two lines of meat-type chickens divergently selected for early (HC line) and late (LC line) antibody responsiveness at 10 days of age to immunization with inactivated pathogenic Escherichia coli bacteria. The question addressed in the study presented here is whether this selection has changed other immunological responses, increasing the overall 'early' immunocompetence. Broilers of the third and fourth generations (S3 and S4) of the selected lines (HC and LC) and a control, unselected line (CT) were vaccinated at 10 days of age with E. coli vaccine, Newcastle virus vaccine (NDV), sheep erythrocytes (SRBC) or bovine serum albumin (BSA). Line-HC chicks exhibited higher antibody titers to E. coli, NDV and SRBC than CT or LC chicks. At 20 days of age HC chicks demonstrated a higher total protein and a higher beta- and gamma globulin levels in their serum. At 21 days of age, HC chicks cleared carbon particles faster than LC chicks. Peripheral blood lymphocytes (PBL) from HC chicks vaccinated with E. coli vaccine, proliferated in vitro more actively in the presence of the stimulating antigen than the PBL of LC chicks. Peripheral blood lymphocytes (PBL) obtained from HC-line chicks exhibited a higher proliferative response to concanavalin A (Con A)-, phytohemagglutinin (PHA)- or pokeweed mitogen (PWM)-stimulation than LC PBL. These results demonstrate that the selection for high or low antibody response to E. coli at a young age resulted also in a significant change in the response of other parameters of the immune system. The high response to E. coli was found to be associated with a high antibody response to other antigens (NDV and SRBC), increased phagocytic activity and increased proliferative response to antigen or mitogens. The selection most probably affected early immunocompetence. PMID- 1441226 TI - C3 fixed in vivo to cornea from horses inoculated with Leptospira interrogans. AB - C3 was detected bound in vivo to the opaque cornea of horses inoculated with killed Leptospira interrogans. Employing epithelial corneal cells isolated from a monolayer in tissue culture, we proved that C3 is fixed in vitro to the intact cell surface after incubation with a fresh equine anti-Leptospira serum. These findings, in addition to the infiltration of cornea with neutrophils and lymphocytes, may explain the mechanisms of tissue damage in recurrent uveitis of horses with leptospirosis. PMID- 1441227 TI - Bovine respiratory syncytial virus-specific immune responses in cattle following immunization with modified-live and inactivated vaccines. Analysis of proliferation and secretion of lymphokines by leukocytes in vitro. AB - Cattle were immunized with vaccines containing modified-live or inactivated bovine respiratory syncytial virus (BRSV) and lymphocyte proliferative responses and cytokine secretion were monitored sequentially. Compared to pre-inoculated values, significant increases in proliferative responses to modified-live BRSV were detectable by Day 7 after the primary immunization with the vaccine containing inactivated BRSV, and by 7 days after the second immunization with modified-live virus. After a third immunization with the respective vaccines, proliferative responses to live BRSV were significantly higher in the group that received modified-live vaccine compared to the group that received inactivated vaccine. Proliferative responses to live BRSV corresponded with the presence of interleukin-2 (IL-2) in the supernatants from BRSV-stimulated leukocyte cultures and there were significantly higher levels of IL-2 in cultures from the group that received modified-live BRSV. An interferon species with the characteristics of interferon-alpha was also present in the supernatants from leukocyte cultures and there were no significant differences between the groups of vaccines. The predominant phenotype of proliferating cells in BRSV-stimulated leukocyte cultures derived from both groups of bovine vaccines was a BoCD4+ T-lymphocyte. These in vitro data suggest that both types of vaccines are capable of stimulating cell-mediated immune responses to BRSV in cattle. PMID- 1441228 TI - Bovine respiratory syncytial virus-specific immune responses in cattle following immunization with modified-live and inactivated vaccines. Analysis of the specificity and activity of serum antibodies. AB - Cattle were immunized with vaccines containing modified-live or inactivated bovine respiratory syncytial virus (BRSV) and serum antibody responses were analyzed. Compared with preinculation values, at Day 14 after two biweekly immunizations with modified-live or inactivated vaccines there were significant increases in BRSV-specific titers in the sera of cattle that received both types of vaccines, as determined by a whole cell ELISA. Using a blocking ELISA and radioimmune precipitation it was determined that there was recognition of the fusion (F) protein by antibodies from cattle that received both types of BRSV antigens: however, virus neutralization assays revealed that only cattle that received modified live virus, either in monovalent or polyvalent vaccines, developed neutralizing antibodies to BRSV after two immunizations. These results indicate that inactivation of BRSV can lead to a dissociation between serological recognition of the F protein and virus neutralization in vaccinated cattle. PMID- 1441229 TI - Purification and characterization of porcine C3. Studies of the biologically active protein and its split products. AB - Separation techniques for obtaining pure and biologically active swine C3 have been improved in this study. Using these procedures and through the further characterization of porcine C3, the possibilities for developing more specific techniques for the analysis of the complement system in swine have been improved. Plasma was initially treated with protease inhibitors, polyethylene glycol (PEG) fractionation, plasminogen-depletion and a rapid chromatographic desalting step. The essential fractionation was carried out by DEAE-Sephacel chromatography. Contaminants were removed by size-exclusion (Sepharose CL-6B)- and hydroxylapatite-chromatography. The final recovery reached 56% with 73% retaining specific hemolytic activity. The amino acid composition (98.33%), the functional compatibility and the secondary structure of fragments and intact protein indicate a high degree of homology with human C3. In contrast with the findings of earlier studies was the considerable immunologic cross-reactivity observed with human C3, and the size difference between the human and the swine C3-beta subunit, which was found to be 10 kDa lighter than the human analogue. The finding that the swine C3b/iC3b/C3c fragments do not separate from C3 by agarose electrophoresis, unlike the human analogues, demonstrated that this commonly used simple parameter for the detection of complement activation cannot be used in the porcine model. PMID- 1441230 TI - Inhibition of lymphocyte proliferation by bovine trophoblast protein-1 (type I trophoblast interferon) and bovine interferon-alpha I1. AB - Bovine trophoblast protein-1 (bTP-1) is a Type I interferon secreted by the bovine trophoblast from about Day 15 of pregnancy. It is not known whether bTP-1 has functional properties in common with other interferons. The aim of the present study was to determine whether bTP-1 inhibits proliferation of lymphocytes induced by mitogens, mixed lymphocyte cultures (MLC) and interleukin 2 (IL-2) and, if so, whether this activity is similar to that of a related interferon, bovine interferon-alpha I1 (bIFN-alpha I1). Stimulation of lymphocyte proliferation caused by phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) was inhibited by bTP-1 and bIFN-alpha I1 without any reduction in cell viability. Maximum or near-maximum inhibition (less than 50%) was achieved at concentrations of 0.5-5.0 nM of bTP-1 and bIFN-alpha I1. Cells stimulated with PWM were less inhibited than cells stimulated with PHA and Con A. Both bTP-1 and bIFN-alpha I1 inhibited MLC to a greater degree than lectin stimulated cells (maximum inhibition was 78% or greater). Also, bTP-1 and bIFN alpha I1 slightly inhibited incorporation of [3H]thymidine ([3H]TdR) induced by the combination of phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA), and calcium ionophore A23187. Finally, bTP-1 and bIFN-alpha I1 had bimodal effects on incorporation of [3H]TdR by IL-2-induced lymphocytes. Incorporation of [3H]TdR was increased at 0.005 nM and 0.05 nM concentrations while higher concentrations caused a slight decrease in [3H]TdR incorporation. Results confirm that bTP-1 inhibits lymphocyte proliferation in a manner similar to that caused by the leukocyte-derived interferon, bIFN-alpha I1. Incomplete inhibition of mitogen induced proliferation and differences in degree of inhibition between various stimulators suggest that bTP-1 and bIFN-alpha I1 preferentially inhibit certain lymphocyte subpopulations. Local inhibition of lymphocyte proliferation caused by bTP-1 may help protect the allogeneic conceptus from immune responses to fetal antigens or regulate the release of cytokines from endometrial lymphocytes. PMID- 1441232 TI - [The scientific activities of a hospital]. PMID- 1441231 TI - Partial purification and characterization of chicken interleukin-2. AB - Chicken interleukin 2 (IL-2) activity was partially purified from conditioned medium produced by culturing chicken splenic lymphocytes in the presence of concanavalin A. The purification procedure included sequential steps of gel filtration chromatography, reverse-phase high-pressure liquid chromatography, and phenyl-sepharose chromatography. Two peaks of IL-2 activity with apparent mol. wt. ranges of 36-39 kD and 17.5-25 kD were eluted from the Sephadex G100 gel filtration column. An increase in IL-2 spec. act. from 14 U mg-1 to between 2000 and 20,000 U mg-1 was obtained for the Sephadex G100 column peaks when subjected to the subsequent steps of the purification procedure. Alkylative reduction of the higher mol. wt. Sephadex G100 column peak (followed by re-chromatography with Sephadex G100), resulted in generation of the lower (17.5 kD) mol. wt. peak, indicating that chicken IL-2 is capable of either dimerizing or forming aggregates with other proteins. Elution of the lower mol. wt. IL-2 activity from a non-reducing sodium dodecyl sulfate-polyacrylamide gel demonstrated an apparent mol. wt. for chicken IL-2 of 20 kD, which confirmed the range of 17.5-25 kD seen with gel filtration. PMID- 1441233 TI - [The psychological training of the students of a military medicine department for their professional activities]. PMID- 1441234 TI - [The characteristics of rendering qualified surgical and specialized medical care during the war in Vietnam]. PMID- 1441235 TI - [Experience in treating maxillofacial wounds (based on army hospital data)]. AB - The article analyses the treatment of 494 patients with maxillofacial wounds. Local anesthesia was applied in 74% of cases, and general one--in 26%. Local anesthesia in 55% of cases was combined with intravenous or intramuscular injections of meperidine that made it possible to assure the treatment of the vast wounds. Simultaneously with the course of surgical treatment 36 patients underwent a primary plastic operation. Laminated stitches were used in 38 cases. The bent wire splints were used to immobilize the fractured fragments of jaw. "Protakril" self-solidified plastics were used in 31 cases to treat gunshot fractures of low jaw. PMID- 1441236 TI - [The characteristics of rendering care to those wounded with vascular gunshot injuries]. PMID- 1441237 TI - [The comparative characteristics of cranioplasty methods using biological materials]. AB - Comparative results were obtained in the experiments conducted on dogs in cranioplasty using allogenic bones, one-piece or small-fragmentized brephoxenotransplants. It was found out that allogenic bones and brephoxenotransplants, when conserved in the solution of 0.2% of formaline and 0.1% of gl. aldehyde, were a perfect material for cranioplasty. These materials ensure a reparative osteogenesis in the recipient's organism after grafting. The process in small-fragmentized brephoxenotransplants is more active and ensures the bone recuperation of the vault of skull in 1.5 years. PMID- 1441238 TI - [The use of intermittent medical plasmapheresis in the combined treatment of severe diseases and injuries at a garrison hospital]. PMID- 1441239 TI - [The rendering of cardiac surgical care to servicemen and the members of their families]. PMID- 1441240 TI - [The possibilities for using new integral indices of the human peripheral blood]. AB - In medical examination of flight personnel two new statistic indexes of integral estimate of changes in peripheral blood were used: integral blood deterioration ratio and entropy of leukocyte blood formula. These indexes have a rather high sensitivity that makes it possible to determine the tendency towards pathological changes in the organism, even if the whole blood picture will be within acceptance limits. PMID- 1441241 TI - [The diagnosis and treatment of neurological disorders in heat shock]. AB - The article examines actual aspects of serious heat injuries in some kinds of military activities, and shows clinical manifestations of nervous system affection in thermal shock. The authors stress the importance of opportune diagnosis for these types of heat injuries, and describe the measures oriented to the correction of neurologic disorders in thermal shocks, as well as its role in complex treatment of this pathology. PMID- 1441242 TI - [Contrast viscosimetry as a current method for the determination of the severity of retinal damage]. PMID- 1441243 TI - [The clinico-immunological validation of associated immunization]. AB - Clinico-immunological studies on men were conducted using associated immunization by pair combinations of 8 commercial national vaccines (typhoid, plague, typhus, smallpox, tick-borne encephalitis, yellow-fever, cholera and sextaanatoxine). As for reactogenicity and immunological efficiency (serological studies), these pair associations can be subdivided into three main groups. The first group consists of pair combinations of vaccines that cannot exert any influence on immunogenicity of cause the development of frequent post-vaccination reaction or temporary disability (typhus, smallpox, tick-borne encephalitis, yellow-fever vaccines). These preparations are completely compatible in every combination. The second group includes plague and cholera vaccines that reduce its immunogenicity under the influence of more active antigens or increase its reactogenicity being associated with typhoid vaccine or sextaanatoxine. The third group is composed of typhoid vaccine and sextaanatoxine that have high reactogenicity and stable serological shifts. Associations of the first group are the most favourable for anti-epidemiological practice. PMID- 1441245 TI - [The outlook for research to improve the activities of the medical service in accidents and disasters (a review of the literature)]. PMID- 1441244 TI - [The efficacy of sodium nucleinate in preventing acute respiratory infections in troop units]. PMID- 1441246 TI - [The evaluation and criteria of body weight standards for servicemen]. PMID- 1441247 TI - [The effect of a milk-processing product on body nonspecific resistance]. AB - Laboratory experiments in rats had shown that the standard ration of the structural food concentrate obtained from milk processing could increase the body resistance of animals by 20-30%. The estimation of the influence exerted by the concentrate was made on the basis of hypoxic and radiobiological models. The authors make a conclusion that application of this concentrate for prophylaxis has good prospects for the future. PMID- 1441248 TI - [The outlook for improved medical control over the health status of the flight personnel in a military unit]. AB - The article studies methodological and methodical questions for improving medical control (MC) over the flight personnel. The authors analyse the main components of MC, i.e. basic control which is built on clinicophysiological methods, and dynamic control which is aimed for estimation of performance characteristics in the process of professional activities. The authors substantiate the structure of the perspective computerized automated system for MC consisting of three functional units: terrain complex of medical operational control, on-board equipment for aircrew health monitoring in flight, expert and diagnosis system for estimation and prognostication of professional health status. PMID- 1441249 TI - [The reasons for divers to cease their occupational work activities]. PMID- 1441250 TI - [A device for the active drainage of wounds and cavities in the postoperative period]. PMID- 1441251 TI - [An improved fixing unit assembly for an electroroentgenographic apparatus]. PMID- 1441252 TI - [An appliance for the x-ray diagnosis of injuries to the collateral knee joint ligaments]. PMID- 1441253 TI - [A scalpel for the lancing of pharyngeal abscesses]. PMID- 1441254 TI - [The protection and strengthening of mental health]. PMID- 1441255 TI - [Nikolai Nikolaevich Savitskii (on the centenary of his birth)]. PMID- 1441256 TI - [Medical service for the land forces of the USA: its organization and utilization principles]. PMID- 1441258 TI - [The Central Military Medical Directorate has been transformed into the Main Military Medical Directorate]. PMID- 1441259 TI - [Mobile search and rescue units]. PMID- 1441257 TI - [The hospital ships of the naval military forces of the USA]. PMID- 1441260 TI - [The methodology of mathematical modelling in military medicine]. PMID- 1441261 TI - [A computer system with an "artificial intellect"]. PMID- 1441262 TI - [The planning of the academic process and of the work organization of the training section of the military department in a medical institute with the use of programming facilities and applied program software]. PMID- 1441263 TI - [The use of applied sorbents in the surgical management of wounds of the extremities]. AB - 970 laboratory experiments, 202 chronic experiments on animals and 102 clinic observations were performed to study the possibilities of sorbents to enhance the efficiency of surgical treatment in gunshot wounds of the extremities. Gravimetric, climatic, morphometrical, microbiological, spectrofluorometric, clinical and roentgenological methods of studies were used for this matter. It was ascertained that the sorbent application contributed to the optimization of the wound process. The studies have proved the advantages of composite sorbent with biologically active supplements: it has a high sorption capacity, pronounced bacteriostatic and local-anaesthetic features. PMID- 1441265 TI - [Amputation of the extremities in obliterating vascular diseases]. PMID- 1441264 TI - [A comparative study of charcoal sorbents for local wound treatment]. AB - The laboratory and medico-biological findings made it possible to choose the most suitable carbonaceous sorbents for local management of wounds, basing on the fact that every carbonaceous material has strictly selected capacity for protein and microbe sorption, and also can be the carrier of the water-miscible drugs. The "Dnieper-MN" carbonaceous fabric and "Aktilen" fibrous sorbent have the best features for sorption. It is possible to use these materials for the construction of bandages to treat wounds and burns which have little exudation. "Karpema" and "AUTM-2" sorbents, which are characterized by the low degree of activation, can be used for the manufacturing of surgical pads. "Karpema" being strong and having a less fiber structure, has a good electrical conductivity and, thus, can be used as medical electrodes. PMID- 1441266 TI - [Hemoperfusion via a xenogenic spleen in the combined treatment of surgical burn sepsis]. PMID- 1441267 TI - [The combined therapy of chronic pyoderma taking into account body immunological reactivity and staphylococcal antibiotic resistance]. AB - Summarizing the results of treatment in 23 patients the authors propose an effective two-staged method to treat chronic pyoderma. This method is based on administration of synthetic peptide of thymus--"thymogen", which is used to correct the immune status and increase sensitivity of staphylococci to antibiotics at the zones of cutaneous affection. The second stage of this method consists in administration of antibiotics in combination with stimulators of phagocytosis and humoral immunity. The results prove the high efficiency of thymogen application in complex management of chronic pyoderma: up to 73.9% of clinic recoveries. PMID- 1441268 TI - [Body immunocorrection when vaccination is contraindicated (a clinico epidemiological validation)]. AB - The article summarizes the results of epidemiological observation which was performed in one of the training units. The goals of this observation were to estimate the prophylactic efficiency of the selected application of Natrii nucleinas in persons with the lowered immunoresistance on the background of antigrip immunization. A high clinico-epidemiological effectiveness ws approved for 10-days administration of the Natrii nucleinas in persons with clinic manifestations of grip and other respiratory infections at the moment of vaccination. It is resulted in the diminishing of the morbidity index, duration and gravity of this pathology in the postvaccinal period. The administration of Natrii nucleinas was experimentally substantiated during this epidemiological observation. PMID- 1441269 TI - [Diagnostic difficulties in pulmonary tuberculosis]. AB - The pronounced pathomorphosis complicates the diagnosis of pulmonary tuberculosis, especially with round growths in lungs. In the author's opinion the reasons that lead to the errors in the diagnosis of pulmonary tuberculosis are the following: as a rule, the diagnosis is made only on the basis of clinico roentgenological data; lack of oncological anxiety; overestimation of trial chemotherapy by means of tuberculostatic medications. In cases of the indeterminate diagnosis it is recommended to arrive at the decision on operation within the shortest possible time. PMID- 1441270 TI - [Methodological and methodical problems in the system of the organization of troop health and hygiene support]. PMID- 1441271 TI - [The basic trends in health protection and rehabilitation for international troops (the Committee on International Troop Affairs of the Council of the Heads of Government of the member states of the Commonwealth of Independent States)]. PMID- 1441272 TI - [The developmental outlook for epidemiological health surveillance in the Armed Forces]. PMID- 1441273 TI - [Pharmacological agents for stimulating the work capacity of flight personnel under stressful duties]. PMID- 1441274 TI - [An experimental and clinical validation of the use of sorption materials in treating infected wounds]. PMID- 1441275 TI - [Scleroplastic operations as a method of preventing the progression of limited degrees of myopia]. PMID- 1441276 TI - [Eye lesions from the components of a regenerative substance]. PMID- 1441277 TI - [The use of soft contact lenses in eye injuries and diseases]. PMID- 1441278 TI - [The dynamics of the thyroid functional indices in adaptation to military service]. PMID- 1441279 TI - [To publish by imperial edict (on the 170th anniversary of the Voenno meditsinskii zhurnal)]. PMID- 1441280 TI - [Boris Konstantinovich Leonardov (on the centenary of his birth)]. PMID- 1441281 TI - [At the sources of the birth of sanitary chemical defense]. PMID- 1441282 TI - [The visit of a medical delegation of the Combined Armed Forces of the CIS to Switzerland]. PMID- 1441283 TI - [Glycosaminoglycans in syrinogomyelia]. AB - Excretion of glycosaminoglycans (GAG) with urine was 2.7-fold decreased in patients with syringomyelia as compared with healthy persons. Patterns of GAG decreased excretion are genetically determined and inherited as dominant features. Content of GAG was decreased in the patients skin, cerebrospinal fluid and brain by 30%, 40% and 20-40%, respectively; content of GAG was increased by 80% in spinal cord where the pathological process was localized. The data obtained suggest that considerable impairment of connective tissue metabolism occurred in syringomyelia. PMID- 1441284 TI - [Isolation and physico-chemical characteristics of ceruloplasmin obtained from murine serum]. AB - Ceruloplasmin was isolated from mice blood serum by means of ion exchange chromatography and gel filtration. Its content in blood was equal to 10-12 mg/100 ml, oxidase activity--9-12 U/mg of protein at E440, molecular mass--161.3 +/- 5.8 kDa. Properties of mice ceruloplasmin were studied as compared with the human and rat glycoprotein, isolated using the similar procedure. PMID- 1441285 TI - [Proteolytic mechanisms in bronchial secretions in rats with bronchial anaphylaxis]. AB - Serine elastase-like proteinase was isolated from rat bronchial secretion, activity of which was increased 2-fold in bronchial anaphylaxis. Effect of histamine, serotonin and hydrocortisone on the enzymatic activity was studied. Regulation of the enzyme activity in bronchial anaphylaxis was considered with relation to patterns of its metabolism as well as depending on efficiency of specific endogenous inhibitor of the proteinase. A procedure for histamine stimulation of alkaline proteinase was developed. PMID- 1441286 TI - [Biochemistry of fructose-2,6-biphosphate--a regulator of carbohydrate metabolism]. PMID- 1441287 TI - [Use of the magnitude of vitamin and vitamin metabolite excretion as indicators of availability of vitamins B2, B6, and niacin]. AB - Alimentary deficiency of riboflavin in rats caused a decrease in excretion of vitamin B2 with urine simultaneously with lowering in daily excretion of 4 pyridoxylic acid (4-PA) and N1-methyl nicotinamide (N1-MNA); these patterns are usually used as indicators of pyridoxine and niacin availability. The similar decrease in excretion of 4-PA and N1-MNA with urine but without alterations in NAD+NADP concentrations in erythrocytes was detected in women deficient in vitamin B2. Content of nicotinamide coenzymes in erythrocytes correlated with excretion of N1-MNA with urine only under normal conditions of riboflavin availability. Use of the criteria involving rates of 4-PA and N1-MNA excretion for evaluation of pyridoxine and niacin deficiency is discussed. PMID- 1441288 TI - [Stomach mucosa prostaglandins in liver cirrhosis]. AB - Distinct decrease in content of prostaglandins PGE, PGF2 alpha and 6-keto-PGF1 alpha was detected in biopsy material, using radioimmunoassay, from gastric mucosal membrane of patients with liver tissue cirrhosis complicated and not complicated by ulcerous disease of stomach or duodenum which correlated with a decrease in secretion of gastric juice (basal and histamine-stimulated secretion). These data suggest considerable impairments of endogenous biosynthesis of prostaglandins in gastric mucosal membrane under conditions of liver tissue cirrhosis, which are of importance in development of ulcerous disease in these patients. PMID- 1441289 TI - [Muscarinic acetylcholine receptors in peripheral human lung tissue: binding characteristics of 3H-quinuclidinyl-benzilate in malignancies]. AB - Binding of muscarinic receptors antagonist 3H-quinuclidinyl benzylate (3H-QNB) was studied in human peripheral lung tissue, obtained after resection of pulmonary carcinoma and partial resection of tuberculoma from surrounding normal tissues (control group). Radioligand binding assays showed that binding of 3H-QNB in lung parenchyma membranes of both normal, healthy persons and patients with cancer was saturable with high rate of affinity. Saturation occurred at 1 nm concentration of the ligand. The Scatchard plot analysis indicated that the high affinity binding site exhibited the following parameters: Kd = 0.33 nm, Bmax = 164.8 fmol/mg in the group of controls: and Kd = 0.63 nm, Bmax = 401.5 fmol/mg in the group of patients with cancer. Maximal amount of 3H-QNB binding sites was distinctly increased in malignization of peripheral lung tissue. The results obtained suggest that increase in concentration of 3H-QNB binding sites may be among the specific patterns of malignant growth in lung peripheral tissue. PMID- 1441290 TI - [Effect of cryoconservation of platelets on polyamine level and cathepsin D activity]. AB - Alterations in activity of cathepsin D as well as in content of polyamines spermine, spermidine, x-fraction (apparently, acetyl spermidine) and putrescine were studied in blood platelets depending on conditions of conservation. The enzyme activity and content of polyamines correlated directly with duration of the cell concentrates storage. Cathepsin D and polyamines appear to be involved in responses to stress adaptation. PMID- 1441292 TI - [Interaction of heparin with defensin, a nonenzymatic cationic protein from neutrophils]. AB - Heparin was shown to form complexes with cation non-enzymatic protein defensin from neutrophils. The complex obtained in vitro did not affect the anticoagulation and fibrinolytic properties of blood, whereas defensin decreased the content of heparin, rates of non-enzymatic fibrinolysis and total fibrinolytic activity while heparin stimulated the anticoagulation activity of blood plasma. Interaction of heparin with defensin appears to be involved in protective mechanism responsible for neutralization of both the heparin anticoagulation activity and the defensin properties related to inhibition of nonenzymatic fibrinolysis. PMID- 1441291 TI - [Antioxidants, lipid peroxidation, and receptor-dependent increase in Ca2+ concentration in human platelets]. AB - Content of tocopherol and total antiradical activity of hydrophobic antioxidants were estimated in human blood platelets. Two hydrophobic antioxidants--tocopherol and ubiquinone were detected in hexane extracts of thrombocytes using thin-layer chromatography. After incubation of thrombocytes with N-ethyl maleimide content of malonyl dialdehyde was increased and of tocopherol--decreased, receptor dependent increase of Ca2+ concentration in cytoplasm was potentiated, while the Ca(2+)-blocking effect of nitroglycerol was decreased. Nitroglycerol did not inhibit the N-ethyl maleimide effect on content of malonyl dialdehyde in blood platelets. Addition of exogenous vitamin E to thrombocytes did not affect the receptor-dependent increase of Ca2+ concentration. Ascorbic acid inhibited the receptor-dependent increase of Ca2+ concentration. The data obtained suggest that nitrates may be used more rationally in combination with antioxidants and/or inhibitors of cyclooxygenase. PMID- 1441293 TI - [Structure-activity determination of physiological reactions of vasopressin and its analogs on the hemostasis system]. AB - Effects of vasopressin, its C-terminal fragments and derivatives on the system of hemostasis were studied in rats. Modification of amino acid sequence in vasopressin molecule led to distinct alterations in main peptide properties. Presence of ring structure in the peptide molecule appears to be obligatory to increase the content of factor VIII in blood, while absence of glycine in side chain caused a decrease in the rate of fibrinolysis and in activity of plasminogen activators. PMID- 1441294 TI - [Thrombolytic effect of urokinase upon various methods of administration into the body]. AB - A preparation of urokinase, obtained from human kidney cell culture, was administered into rats at a single dose of 5,000-10,000 U/200 g of body mass in a variety of ways using intravenous, intraperitoneal and subcutaneous inoculations. After intraperitoneal and subcutaneous administrations an increase of fibrinolytic activity in blood was more long-term although less distinct; the phase of reactive hypercoagulation was only slightly detected within 24 hrs after these procedures. Thrombin-produced provocation of thrombosis led to a lesser ratio of death in these animals as compared with the animals group administered intravenously. However, thrombolytic effect of similar doses of urokinase was the highest in intravenous administration. The fibrinolytic activity correlated well with content of the antigen (enzyme) in blood but not with the antiplasmin content in all the procedures used. PMID- 1441295 TI - [Structural components and activity of erythrocyte membrane ATPase from albino male rats under the effect of noise and simultaneous treatment with the synthetic antioxidant 3,5-ditertbutyl-4-hydroxyphenylpropanol (gamma-propanol)]. AB - Repeated administration of synthetic antioxidant gamma-propanol, 3,5-ditertbutyl 4-hydroxyphenyl propanol, into rats under conditions of acoustic noise led to increase in content of phospholipids, to decrease in cholesterol level simultaneously with inhibition of ATPase activity in erythrocyte membranes. The initial hypocholesterolemic effect of gamma-propanol under conditions of acute acoustic stress was replaced by hypercholesterolemia in long-term experiments within more than 4 weeks. PMID- 1441296 TI - [Participation of protein C in reaction of the anti-coagulant system to intravenous administration of thrombin and thromboplastin to rats]. AB - Dynamics of protein C concentration was studied in rat blood after administration of thrombin and thromboplastin. Administration of 0.5 ml 1% thromboplastin caused fast decrease of protein C concentration, down to 60% of the initial level, within 3 min, while activity of factor V reached the minimal rate (30%) within 5 min. Content of protein C returned to the initial level in blood within 2-2.5 hrs and of factor V--within 6 hrs. After administration of thrombin 3 NIH in content of protein C was decreased to 91.3% whereas heparin was released only after injection of 6 NIH. The data obtained suggest that the protein C system responded earlier to occurrence of thrombin in circulation as compared with the neurohumoral regulators of the anticoagulation system; the protein C system is one of primary mechanisms of the antithrombosis defence. PMID- 1441298 TI - [Features of lipid metabolism impairment in chronic alcoholic intoxication]. AB - Long-term administration of ethanol into animals within 1-6 months resulted in distinct alterations of blood serum fatty acid composition as well as in elevation of the saturation rate simultaneously with a decrease of fatty acid polyunsaturation. Calculated coefficients, which included ratios between fatty acid with various rates of unsaturation, were highly informative. Alterations of fatty acid composition in blood serum, registered during observations, reflected the state of fatty acid metabolism in tissues. Analysis of fatty acid spectrum in blood serum enabled to evaluate the severity of impairments in liver tissue and pancreas under conditions of alcohol intoxication: increase in the rate of phospholipid catabolism, in content of cholesterol, triglycerides and total lipids was observed both in blood serum and liver tissue. These impairments of lipid metabolism may produce alcohol hepatitis, which is the basis for liver tissue alcohol cirrhosis. PMID- 1441297 TI - [Phenomenon of adapted stabilization of structures and the role of heat shock proteins in its mechanism]. AB - Mechanisms, responsible for distinct increase in rat heart tissue resistance to reperfusion paradox and toxic concentrations of catecholamines and Ca2+, were developed in the heart after repeated stress actions. Sarcoplasmic reticulum and mitochondria isolated from heart cells of adapted animals were highly resistant to autolysis, while nuclei--to the impairing effect of single-strand exogenous DNA. These alterations were designed as a phenomenon of adaptive stabilization of structures (PhASS). Accumulation of heat shock proteins was found to be of importance in mechanisms of PhASS. Development of PhASS was accompanied by an increase in resistance of myocardium to ischemic necrosis. PMID- 1441299 TI - [Preparation and use of an affinity sorbent containing phenylboric acid, for separation and quantitative determination of glycated hemoglobin]. AB - m-Aminophenylboric acid, attached to epoxy-activated diasorb, developed a highly effective sorbent intended to separation and quantitative estimation of glycated hemoglobin. The procedure developed is reproducible, fast and may be used in mass scale examination of people for occult diabetes. Temperature and pH of buffers used did not affect significantly the data obtained. PMID- 1441300 TI - [Catalytic properties of induced L-lysine-alpha-oxidase]. AB - Regulation of biosynthesis of L-lysine-alpha-oxidase from Trichoderma sp using biostimulators was studied. Specific activity of L-lysine-alpha-oxidase was increased 2.7-fold in presence of biostimulators; this occurred due to induction of the enzyme, properties of which were described previously. Catalytic and physico-chemical properties of the enzyme studied were not altered after addition of stimulators into the cultivation medium of the producing strain. Small amounts of L-lysine-alpha-oxidase isozyme were detected in the medium during cultivation; the isozyme was less active and had lower molecular mass as compared with the enzyme studied. PMID- 1441301 TI - Repeat plateletpheresis: the effects on the donor and the yield. AB - Requirements for HLA ot otherwise matched single-donor platelets may sometimes require repeat plateletpheresis of an individual donor. AABB standards permit the repeat collection of platelets by plateletpheresis of a single donor at 48-hour intervals, whereas recent recommendations from England state that a donor should not donate platelets more often than 12 times a year. To assess the effects of repeat plateletpheresis on the donor, we have studied the hematological indices and the product yields following every other day plateletpheresis of 13 normal donors who gave a total of 10 times during 22 days. The platelet count decreased in every case, with the lowest values reached at the third donation (day 5). The pre-donation count averaged 225 +/- 53 x 10(9)/l decreasing to 174 +/- 27 x 10(9)/l at the time of the 3rd donation then increasing by the 6th donation to 198 +/- 46 x 10(9)/l. The yield in the product decreased from 3.2 +/- 1.3 x 10(11) on day 1 to 2.6 +/- 0.8 x 10(11) for the third donation, returning thereafter to higher values. In spite of the expected and apparent stimulation of platelet production through feedback, the counts did not rebound above starting levels indicating a basic homeostatic mechanism. The donor WBC showed minimal changes during the study period, however there was a significant increase in the total number of lymphocytes by the 3rd procedure; this was corrected by the fifth procedure. The absolute number and ratio of T4 (helper) and T8 (suppressor) lymphocytes did not change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441302 TI - Correlation between anti-HBc titers and HBV DNA in blood units without detectable HBsAg. AB - Hepatitis B virus (HBV) DNA was tested for in 294 blood units which had antibody against hepatitis B core antigen (anti-HBc) as the isolated serological marker of HBV infection. After amplification by polymerase chain reaction, HBV DNA was detected in 12 (6.9%) of 175 units that were positive for anti-HBc with hemagglutination inhibition titers greater than or equal to 2(6), significantly more often than in none of 119 units with titers less than or equal to 2(5) (p less than 0.01). These results indicate that the exclusion of blood units with isolated high-titer anti-HBc would be effective for further decreasing the risk of posttransfusion hepatitis B. PMID- 1441303 TI - Diversity of human anti-D monoclonal antibodies revealed by reactions with chimpanzee red blood cells. AB - Fifty-three human anti-D monoclonal antibodies (mAbs) revealed a striking diversity of reactions in tests with panels of chimpanzee red blood cells (RBCs) of various R-C-E-F blood group phenotypes (counterparts of the human Rh-Hr groups). The reactivities of these antibodies, which depended on the agglutination technique used, could be classified into four main types. These patterns of reactivity of anti-D mAbs with chimpanzee RBCs showed only limited correlation with types of reactions observed with human D variant RBCs. Primate red cells may, therefore, constitute an independent test system for subclassification of human monoclonal antibodies. Comparison of reactivities of human anti-D mAbs with chimpanzee and human D variant RBCs confirms the homology between the chimpanzee Rc, and the human D antigens. The chimpanzee Rc shares with human D the epitopes epD5, epD6/7 and epD8, but lacks epitopes epD1, epD2, epD3 and epD4 of the Rh mosaic, thus resembling the human D variants IVb and Vc. PMID- 1441304 TI - Thrombocytopenia due to platelet glycoprotein IIb/IIIa-reactive autoantibodies non-reactive with platelets from EDTA blood. AB - We describe 2 patients with thrombocytopenia and autoantibodies in the blood against platelet membrane glycoprotein (GP) IIb/IIIa, in whom reactivity of the antibodies with their antigen was greatly diminished in the presence of sodium EDTA. One patient also showed a marked thrombocytopathy, suggesting a functional blocking of GP IIb/IIIa by these autoantibodies. These observations show that some immunologically important autoantibodies can easily be missed in routine serological investigations in which EDTA blood is used, obscuring the autoimmune nature of a thrombocytopenia and possibly of a thrombopathy as well. PMID- 1441305 TI - TSEN: a novel MNS-related blood group antigen. AB - We report an antibody (anti-TSEN) that recognizes an antigen (TSEN) at the unique amino acid sequence that results from the junction of GPA58 to GPB27 if the GPB carries the S antigen. Red cells from several unrelated donors that possess this specific GP(A-B) hybrid molecule were agglutinated by anti-TSEN. Since a synthetic peptide with the amino acid sequence at this junction (Pro-Glu-Glu-Glu Thr-Gly-Glu-Met-Gly-Gln-Leu-Val-His-Arg) specifically inhibited anti-TSEN, it must detect an antigen within this novel amino acid sequence. The TSEN antigen has been provisionally assigned the MNS blood group system number 002.033 on behalf of the ISBT Working Party on Terminology for Red Cell Surface Antigens. PMID- 1441306 TI - MINY: a novel MNS-related blood group antigen. AB - We report an antibody (anti-MINY) that recognises a novel low-incidence MNS related blood group antigen. Anti-MINY agglutinates all Hil-positive red cells tested (Mi.III, Mi.V, Mi.VI, GP.Kipp, GP.Mor and AG) and Hil-negative TSEN positive red cells (Mi.IV, JR, JL, Oca. and Rag.). All MINY-positive red cells possess glycophorin A-B hybrid molecules. The MINY antigen occurs at the unique amino acid sequence which results from the junction of glycophorin A58 to glycophorin B27 regardless of whether the glycophorin B gene encodes methionine or threonine at amino acid residue 29 of normal glycophorin B. The MINY antigen has been provisionally assigned the MNS blood group system number 002.034 on behalf of the ISBT Working Party on Terminology for Red Cell Surface Antigens. PMID- 1441307 TI - Autologous blood donation by patients with cardiovascular disease. PMID- 1441308 TI - Autologous blood transfusion in thoracic surgery: a survey of 667 patients. PMID- 1441309 TI - Cell age characterization of erythrocytes in the buffy coat. PMID- 1441310 TI - Safety of the antibody screening test as the sole method of pretransfusion testing. PMID- 1441311 TI - Nomenclature for factors of the HLA system, 1991. PMID- 1441312 TI - Prevalence and classification of anemia in elective orthopedic surgery patients: implications for blood conservation programs. AB - We audited 281 consecutive orthopedic patients scheduled for surgery for whom blood type/cross-matching was requested over a 6-month period. One hundred and sixty-two patients predonated autologous blood at University Hospitals of Cleveland, and 34 (21%) of these were anemic [hematocrit (Hct) less than or equal to 39%] at initial donation. Twelve (35%) of these 34 anemic autologous blood donors subsequently received homologous blood. In contrast, 18 (15%) of 128 nonanemic autologous blood donors received homologous blood (p = 0.05). In 119 patients who did not donate autologous blood, 39 (33%) were anemic at admission. Of these, 22 (56%) received homologous blood. In the 80 remaining nonanemic patients, 33 (41%) received homologous blood (p = 0.119). Analysis of discharge Hct indicates that 31 (12%) of 263 evaluable patients were possibly transfused inappropriately. The anemias of a cohort of 30 autologous donors were analyzed: 5 had rheumatoid arthritis without iron deficiency. Nine (30%) others had evidence of iron deficiency. Sixteen (53%) had an unclassified anemia of chronic disease. We conclude: (1) the high rates of homologous blood exposure indicate a need for innovative blood conservation strategies in anemic autologous blood donors; (2) the prevalence of anemia and the high rates of homologous blood exposure in anemic patients who did not donate autologous blood demonstrate a need for early recognition and treatment in order to procure autologous blood and reduce homologous blood exposure; (3) the presence of inappropriate autologous and homologous transfusions demonstrates a need for more effective physician education programs that emphasize 'no blood transfusion' as an alternative to enhance blood conservation effectiveness. PMID- 1441313 TI - Autologous blood donation in nonorthopaedic surgical procedures as a blood conservation strategy. AB - Autologous blood donation in many nonorthopaedic procedures is controversial. Our study of 408 consecutive such procedures could be divided into two groups. In group I, the anticipated probability for homologous blood transfusion was very low (less than 5%): vaginal hysterectomy and miscellaneous gynecologic procedures, obstetrical delivery, mammoplasty and cholecystectomy. In group II, the anticipated probability for homologous blood transfusion was high (greater than 5%): open heart and vascular surgery, neurosurgery, mastectomy, abdominal and radical hysterectomy, and extensive urologic procedures. We conclude that for procedures in which the blood transfusion probability is very low, autologous blood donation should not be encouraged; this practice should be promoted in procedures in which the blood transfusion probability is 'high' (i.e. greater than 5%), with emphasis on maximizing autologous blood collection in order to minimize homologous blood transfusion. PMID- 1441314 TI - [Acetylsalicylic acid ultraphonophoresis in the treatment of the pain syndrome in patients with lumbar osteochondrosis]. AB - Data are reported of an experimental-clinical substantiation and therapeutic use of acetylsalicylic acid ultraphonophoresis of pain syndromes of radicular and reflex genesis in 144 patients with lumbar osteochondrosis. Improvement was noted in 57.3% in severe pain, 31.2% in moderate pain, and 75% in mild pain. Aspirin ultraphonophoresis was effective in pain syndrome of radicular genesis in 71% of cases and in 60.5% of reflex genesis. PMID- 1441315 TI - [Experience with the compulsory treatment of patients with pulmonary tuberculosis and alcoholism]. AB - Patients with alcoholism and tuberculosis suffer most frequently of alcoholism stage II. Tuberculosis effects unfavourably the course of alcoholism. Most frequently acute alcohol psychoses appear in patients with pulmonary tuberculosis showing a severe and prolonged course. Alcoholism effects the process of treatment of tuberculosis: healing of cavernosis is noted in 9.8%, abacillation- in 11.5%. Compulsory treatment of patients with alcoholism and tuberculosis should be carried out in large antitubercular clinics with special wards for these purposes. Decisions should be made by courts. In narcological clinics special wards for the treatment of the above mentioned patients should be singled out. PMID- 1441316 TI - [The characteristics of the initial period of alcohol consumption in men with venereal diseases of the urogenital system]. AB - Results indicate that the average age of first consumption of alcohol by juveniles is in direct and to a certain degree in "competent" dependence on some external parameters: education, family position and oth. Early alcohol "start" produces the most negative effect on the subsequent low professional-social status and also on the progression of alcoholism an essentially "enhances" their admission to venereal clinics for specific diseases of the urogenital system. PMID- 1441317 TI - [Phytotherapy in rheumatology (a review of the literature)]. PMID- 1441318 TI - [Syncopes: their classification, clinical picture and treatment (a lecture)]. PMID- 1441319 TI - [The differentiated phytotherapy of patients with duodenal peptic ulcer]. AB - Resulted are analysed of complex treatment of 103 patients with duodenal ulcer. Infusions and concoctions of medicinal plants were used. The regimen of administration and composition of the cocktail from herbs depended on the character of gastric secretion and dyskinesia of the gastroduodenal zone as well as on the presence of concomitant diseases; cholecystitis, gastritis, hepatitis, pancreatitis, enterocolitis. Intragastric drip administration of the concoctions and infusions of medicinal plants favour scarring of duodenal ulcers and reduction of the number and duration of recurrences. PMID- 1441320 TI - [Modern principles in designing models of a healthy life style]. PMID- 1441321 TI - [Factors that facilitate the infection of medical workers with viral hepatitis B]. AB - The author analyzes of 180 physicians, nurses, laboratory workers, technicians, carriers of HB A, revealed by radioimmunoassay and a control group of non carriers. Different factors are discussed favouring viral hepatitis B, namely, donorship, minor traumas, rubber gloves as a means of protection, instruments, syringes, needles, inadequate provision with washing and disinfection means. Knowledge of data on the real hazards of viral hepatitis B infection among the medical personnel is of major importance. PMID- 1441322 TI - [Immune anti-Pseudomonas aeruginosa blood preparations (a review of the literature)]. PMID- 1441323 TI - [The dynamics of the general morbidity of the population of Belarus before and after the accident at the Chernobyl Atomic Electric Power Station (1985-1989)]. PMID- 1441324 TI - [Humoral immunity in young hypertension patients]. AB - The state of humoral immunity was investigated in 72 young-age patients suffering of hypertensive disease. It was established that there occurred an increase of the level of immunoglobins, circulating immune complexes and antibodies to lipoproteids of low density in hypertensive disease. This indicates the importance of immunological changes in the pathogenesis of hypertensive disease. PMID- 1441325 TI - [Laser endovascular recanalization (a review of the literature)]. PMID- 1441326 TI - [The optimization of the hypotensive therapy of hypertension patients taking into account the central hemodynamics and functional tests with obzidan and prazosin]. AB - A study of 52 patients with hypertensive disease (grade II, age--from 30 to 50 years; men--32, women--24) using functional tests with physical loads revealed that pronounced hemodynamic changes were seen in patients with the hyperkinetic type of hemodynamics. Obsidan and prazosin reduced the degree of responses to physical loads, economy of energy expenses, increased tolerance to physical work. Association of pharmacological tests with functional physical loads in patients with hypertensive disease allows to realize selection of hypotensive drugs depending on the hemodynamic variant of the course of the pathological process and evaluate the adequacy of dosages for treatment courses. PMID- 1441327 TI - [The attitude of rheumatoid arthritis patients before treatment: social psychological research]. AB - The authors developed a special questionnaire for examination of the attitude of patients to different procedures, methods of treatment, diet, attitude to different levels of medical services, self-treatment. An anonymous study of 125 patients with rheumatoid arthritis was carried out. Many respondents were not satisfied with organization of the treatment, in particular, the outpatient variant. The causes of inadequate treatment and ways for treatment improvement are discussed. PMID- 1441328 TI - [The efficacy of treating peptic ulcer patients with trichopol and dalargin]. AB - A study of 90 patients with endoscopically proved duodenal ulcer revealed that dalargin and trichopol+dalargin treatment resulted in early scarring of the ulcer and control of gastroesophageal and duodenogastric reflux in the majority of patients. Gastroduodenitis symptoms were not eliminated in a half of all patients. It was shown that persistent manifestations of gastroduodenitis remained in patients with a pronounced pyloric helicobacteriosis and a high titer of antibodies to cells of the gastric mucosa. PMID- 1441329 TI - [New tableted protein products in the treatment of peptic ulcer patients and the dynamic indices of the glutathione system]. AB - The authors investigated the content of reduced glutathione, activity of glutathione peroxidase, glutathione transferase, glutathione reductase, glucoso-6 phosphate dehydrogenase in the liver tissue, gastric mucosa of rats with experimental ulcer and in the blood of patients with gastric and duodenal ulcer in the course of treatment using new protein tableted products. Experimental investigations were conducted on 96 white rats, clinical studies in 128 patients and 59 healthy persons. It was shown that high therapeutic efficiency of these new tableted products, their normalizing effects on the glutathione system indices are important. PMID- 1441330 TI - [The radiodiagnosis of the indicators of pancreatic cancer]. AB - For suspicion of pancreatic cancer 84 patients were subjected to ultrasonic examination, computerized tomography, x-ray of the stomach and duodenum and as indicated endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography combined with external cholangiostomy. The semeiotics of cancer of the pancreas was evaluated on the basis of radiation methods. Practical recommendations on the diagnosis and scope of surgical treatment as assessed preoperatively are given. PMID- 1441331 TI - [The functional-morphological changes in the kidney and ureter of patients with congenital ureterohydronephrosis]. AB - Complex methods were used to examine 80 patients with congenital ureterohydronephrosis due to obstruction of the juxtavesical portion of the ureter. It was established that at different stages of the disease the ureteral wall develops intravascular, proper vascular and extravascular disorders, of the hemomicrocirculation and disorders of tissue trophics accompanied by functional changes in the kidney and ureter. PMID- 1441332 TI - [Changes in the complement system in acute streptococcal infection]. AB - Results are reported of a study of relationship of complement level, unspecific adaptative reactions, number of circulating immune complexes and some cellular parameters of the immunogram in patients with different forms of streptococcal infection. Different changes were found in acute and chronic forms of the disease. The possible mechanisms of development of these disorders are discussed. PMID- 1441333 TI - [A structural analysis of hemato-encephalic barrier function in bacterial meningoencephalitis]. AB - A correlation analysis of the content of metals in the cerebrospinal fluid in 70 patients with bacterial meningoencephalitis showed that an increase of permeability of microvessel walls for macro- and microelements is accompanied by a reduction of the regulating activity of barrier structures. Pathomorphological examination of the brain by the method of scanning electron microscopy revealed structural changes of the microvessel walls as the basis of disorders of the barrier-transport function. PMID- 1441334 TI - [The sterility of blood products manufactured in Ukraine]. AB - The author reports results of examination for sterility of 3100 series (7343 samples) of hemocorrectors that were received for State control from zonal blood transfusion stations in the Ukraine from 1987 through 1990. Four of them proved non-sterile. Strict surveillance for aseptics and antiseptics at all stages of the technological process will ensure sterility of all hemotransfusion media obtained from the blood transfusion services. PMID- 1441335 TI - [The significance of beta 2-microglobulin for the diagnosis of preleukemic states in workers of the chemical industry]. AB - A study is presented of 89 workers contacting with benzene and its derivatives and 98 workers without contacts with chemical substances. Radioimmunological assay of peripheral blood B2-microglobulin was carried out. Persons with a length of work over 10 years contacting with anilin and its derivatives showed a marked increase of B2-microglobulin in the blood serum as well a marked reduction of leucocyte number. It is considered that leucopenia with granulocytopenia and marked increase of B2-microglobulin is regarded as a preleucosis state. PMID- 1441336 TI - [The alkaline phosphatase and aminotransferase activity of the blood serum and liver in rats with chronic poisoning by the dust from a mineral wool made of ferronickel slag]. AB - The authors investigated the activity of alkaline phosphatase, alanine- and aspartate-aminotransferases of the blood serum, mitochondria and postmitochondrial fraction of the liver in conditions of administration of mineral cotton from ferronickel slag. It was shown that 1 and 3 months after introduction of mineral cotton dust changes occurred in the activity of these enzymes. Restoration of these enzymes occurred 6 months after introduction of mineral cotton dust. PMID- 1441337 TI - [The modelling of the extrinsic allergic alveolitis of woodworkers]. PMID- 1441338 TI - [A hygienic evaluation of a filter-ventilation installation from the Kemper firm for purifying the air in metal arc welding]. AB - It was found that "Kemper" devices absorb efficiently noxious substances released during arc welding of metals. Conditions for maximum efficiency of the "Kemper" devices are described. PMID- 1441339 TI - [The combination of taking acetylsalicylic acid and a complex of physical factors in the rehabilitative treatment of patients with ischemic heart disease]. AB - The efficacy of physiotherapeutic methods in association with preliminary aspirin intakes was examined in 276 patients with ischemic heart disease. Results indicate that the main clinicofunctional and laboratory indices showed a positive dynamics. The above treatment is considered perspective in the restorative treatment and secondary prophylaxis of patients with ischemic heart disease. PMID- 1441340 TI - [The effect of antioxidants on the nonspecific inflammatory component in rheumatoid arthritis patients]. PMID- 1441341 TI - [Nonspecific aortoarteritis with involvement of the pulmonary arteries]. AB - Considering the common aspects of tissue structure of the aorta and pulmonary artery the authors suggest that in unspecific aortoarteritis in the form of generalized arteriopathy, involvement of pulmonary artery is real. Analysed were 45 autopsy cases. In 31 cases vessel changes of two kinds were seen: destructive proliferative and sclerotic. Not all cases of sclerotic changes may be explained by lesser circulation hypertension and, thus, the reported data evidence frequent involvement of the pulmonary arteries with development of generalized pathology of the vascular system. PMID- 1441342 TI - [The pathomorphogenetic characteristics of the wall of the common bile duct in cholestasis]. AB - Data are presented on the reversibility of pathological changes of the common bile duct, causes and criteria of reversibility. Consideration of four stages of pathomorphogenesis of the common bile duct wall may be of help in the choice of surgical tactics in surgical intervention on the common bile duct. PMID- 1441343 TI - [Liquid-crystal thermography in the diagnosis of peptic ulcer]. AB - The authors studied the aspects of the thermographic picture of the skin, abdomen in patients suffering of gastric and duodenal ulcer as compared with endoscopic and roentgenological methods, their dynamics in the course of treatment. The method of fluid crystalline thermography is recommended as a diagnostic test in conditions of limited diagnostic opportunities. PMID- 1441344 TI - [A treatment method for patients with reflux esophagitis (an invention,copyright No. 1607825)]. AB - The authors developed a method of complex treatment of patients with reflux esophagitis consisting in introduction via a probe of cooled 0.25% collargol solution and rose oil after intake of dimetpramide and simultaneous electrostimulation of the lower third of the esophagus. This method of treatment allows to control rapidly the pain syndrome, enhance treatment time and prolonged remission to 24 hours and more. PMID- 1441345 TI - [The characteristics of chronic bronchitis in workers in ferrous metallurgy enterprises]. AB - Results of clinico-functional examination of workers of metallurgical plants confirmed early development and severe course of chronic bronchitis in this category of workers. The polyetiological aspect of chronic bronchitis is suggested. Changes of the pleura and pneumosclerosis which often accompany chronic bronchitis impede the differential diagnosis with interstitial form of pneumoconiosis. Diagnostic criteria of chronic bronchitis in metallurgists should be determined with consideration of concrete working conditions, endogenous factors of risk in the development of the disease and possible variants of the course. PMID- 1441346 TI - [The results of bronchoscopy in patients of different ages with chronic bronchitis]. AB - Bronchological examination of 1769 patients with chronic bronchitis (CHB) of different age groups revealed that the development of that or another form of endobronchitis (catarrhal, purulent, atrophic) did not depend on the age, duration of disease and other causes. It may be suggested that the genetic predisposition to development of definite forms of endobronchitis. Apparently, most rigidly determined is the development of the atrophic form of endobronchitis as its frequency was similar in all groups, in different forms of CHB. PMID- 1441347 TI - [Enterosorption in the treatment of chronic kidney failure in patients with surgical diseases of the kidneys]. AB - Enterosgel was used in 89 patients with different stages of renal failure treated surgically and medically. It is concluded that isolated or complex detoxication using enterosgel is a perspective approach in the treatment of patients with surgical renal diseases complicated by chronic renal failure. The use of enterosorption in the preoperative period allows to perform operative intervention in situations when infusion treatment by traditional methods was not sufficient. PMID- 1441348 TI - [Clinico-epidemiological and laboratory indices in icteric forms of viral hepatitis B and C]. AB - Icteric form of acute viral hepatitis B (VHR) and C (VHC) were characterized by similar epidemiological data and clinical symptoms, frequency of concomitant diseases, disorders of biochemical values of the blood serum. VHC as distinct from VHB was more frequent in women and was characterized by a short incubation period, prevalence of mild forms. The duration and frequency of revealing blood serum markers of viral hepatitis B are of major importance for differentiation between VHC and VHB. PMID- 1441350 TI - [The importance of research in geriatric pharmacology for practical medicine]. PMID- 1441349 TI - [Neuroendocrine and neurotrophic changes in patients with craniocerebral trauma and fractures of the long bones]. PMID- 1441351 TI - [The medical rehabilitation at Alushta Health Resort of patients coming from areas of increased radiation activity]. PMID- 1441352 TI - [The scientific validation of the differentiated demand of the population for specialized hospital care and an increase in its effectiveness]. PMID- 1441353 TI - [The results and prospects of preventing arterial hypertension in Ukraine]. AB - An analysis is presented of the status of arterial hypertension prophylaxis in the Ukraine. Drawbacks in solution of this problem are discussed: diagnosis is incomplete, prophylactic management of hypertensive disease is inadequate. Ways and means of improving the diagnosis and prophylaxis of hypertensive disease in the Ukraine including better remuneration of the medical personnel and interests of the population in preserving their health are discussed. PMID- 1441354 TI - [The problems of sanatorium care for tuberculosis patients]. PMID- 1441355 TI - [Vadym Mykolaiovych Ivanov (on the centenary of his birth)]. PMID- 1441356 TI - [The development of the ideas of Academician V. M. Ivanov in modern oncology]. PMID- 1441357 TI - [From the Yekaterinoslav Higher Courses for Women to the medical college]. PMID- 1441358 TI - [The pathogenetic mechanisms of the development of glomerulonephritis]. PMID- 1441359 TI - [The iodine level of the environment and the risk of developing thyroid diseases]. PMID- 1441360 TI - [The possible significance of immunological disorders in the pathogenesis of paroxysmal supraventricular tachycardia in patients with the Wolff-Parkinson White syndrome]. PMID- 1441361 TI - [The right ventricle and tachyarrhythmias. The structural-functional characteristics studied by radionuclide ventriculography]. AB - Radionuclide ventriculography was used to evaluate the functional structural parameters of the right ventricle systole and diastole in 100 patients with paroxysmal tachyarrhythmia without signs of cardiac insufficiency (42 with cardiac fibrillation, 35--supraventricular tachycardia, 23--with ventricular arrhythmia). Results indicate that radionuclide ventriculography allows to evaluate objectively the functional state of the right ventricle in patients with paroxysmal tachycardia, detect early signs of deterioration of its hemodynamic productivity and contractile capacity in patients refractory to treatment of cardiac arrhythmias. PMID- 1441362 TI - [The significance of the antioxidant properties of emoxipin in the combined treatment of patients with chronic heart failure]. AB - It was found that emoxypin (40 mg daily) with nitrates of prolonged action and corinfar used in 87 patients with chronic cardiac insufficiency (CCI) reduces the concentration of primary and secondary products of lipid peroxidation to control levels which is not observed when only corinfar and nitrates of prolonged action were used. Simultaneous use of prazosin and emoxypin favoured balanced oxidant antioxidant system of the body. PMID- 1441363 TI - [The effect of chenotherapy on the reservoir function of the gallbladder in cholelithiasis patients]. AB - The effect of chenodeoxycholic acid (CDCA) on the reservoir function of the gallbladder was studied in 46 patients with cholesterol cholelithiasis. There was a dependence between a clear increase of filling of the gallbladder in patients treated by this method with subsequent sharp reduction of its size and development of dyspepsia and diarrhea. In 14 patients increase of the gallbladder against the background of chemotherapy was not authentic but no dyspeptic phenomena occurred. Thus, decompensation of the reservoir function of the gallbladder in patients with cholelithiasis against the background of chemotherapy are manifested by a significant increase of the gallbladder size with subsequent emptying of bile into the duodenum and development of collagenous diarrhea. PMID- 1441364 TI - [Ecological changes and the epidemic process]. PMID- 1441365 TI - [Disorders of the bioenergetics and microcirculation in the gastric mucosa in peptic ulcer with concomitant involvement of the hepatobiliary system]. AB - The histological structure, distribution of neutral glycoseaminoglycanes, the content of glycogen in the cells, activity of succinate dehydrogenase, cytochromoxidase, magnesium-dependent ATP-ase, alkaline phosphatase, lactate dehydrogenase were studied in the biopsies of the gastric mucosa removed from the anterior third of the anterior part of its body in 104 patients. RESULTS: essential decrease of the enzymes of oxidative phosphorylation, increased reaction to lactate dehydrogenase, inhibition of enzymes controlling the microcirculation in the gastric mucosa in ulcer disease. These changes deteriorate in elderly patients as well as concomitant diseases of the hepatobiliary system. PMID- 1441366 TI - [Differentiated immunocorrective therapy in nonspecific ulcerative colitis]. AB - A comparative study of the clinico-immunological efficacy of steroid hormones and thymus drugs in 50 patients with unspecific ulcerative colitis of different activity grades revealed that their efficacy was not similar at different phases of the disease and depended on the activity of the inflammatory process. Corticosteroids were more effective in inflammatory-destructive changes in the mucosa of the large intestine while in mild inflammation with prevalence of ulcerative-reparative processes, immunomodulators (thymalin) are preferred. PMID- 1441367 TI - [The participation of the eicosanoid system in the formation of bronchial obstruction in chronic bronchitis]. PMID- 1441368 TI - [The significance of risk factors in the development of disorders of the cerebral venous circulation]. AB - The state of venous brain circulation in patients suffering of arterial hypertension, excessive weight, hyperlipidemia, ischemic heart disease was investigated using laboratory instrumental methods of examination (rheoencephalography, conjunctival biomicroscopy, determination of lipids in the blood serum and oth.). It was established that subjects with risk factors show often instability of the brain venous tone, while patients with initial signs of brain vessel insufficiency show signs of hypotension. These changes may not be clinically overt, have a compensatory character and diagnosis often requires instrumental methods of examination. PMID- 1441369 TI - [The prevalence of strokes among the native population of the Transcarpathian area]. PMID- 1441370 TI - [The structure and seasonality of strokes in the Central Asian region]. AB - An analysis is presented of case histories of 1475 patients with disorders of the cerebral blood circulation (ischemic stroke--93.9%, hemorrhagic stroke--6.1%). Acute disorders of the cerebral blood circulation prevailed in males up to 50 years of age. The main cause was hypertensive disease (47.3%), atherosclerosis- 35.8% and their combination--12.6%. Maximum incidence of stroke in Middle Asia region was noted during winter-spring period (January, February, March, April), minimum incidence during the summer-autumn period. PMID- 1441371 TI - [Computed tomography in the diagnosis of lumbosacral radiculitis]. PMID- 1441373 TI - [The risk of the occurrence of diabetes based on the data from a genealogical study of the parents]. AB - A study of the Kharkov population revealed the effect of parent exogamy for liability of the progeny to diabetes mellitus that was more pronounced in sons than in daughters. Minimum genetic effect on the formation of diabetes mellitus concerns the group of reduced exogamy. In type I diabetes mellitus, the maximum genetic effect concerns the group of moderate exogamy, in type II diabetes--the group of elevated exogamy. PMID- 1441372 TI - [The significance of the functional status of the crural muscles in the pathogenesis of the postthrombophlebitic syndrome]. AB - Venous stasis, disorders of oxygen metabolism and other disturbances in the post thrombophlebitic syndrome result in reduction of the contractile function of the crus, i.e. muscle pumping capacity. Mutual influence of these factors result finally in the development of the so-called "vicious circle". Results of a study of 90 patients with different stages of the post-thrombophlebitic syndrome show a clear correlation between the stage of the disease and degree of reduction of the functional capacity of sural muscles. Measures for restoration of the contractile capacity of the crural muscles are advocated. PMID- 1441374 TI - [Lipid peroxidation in the lymphocytes of guinea pigs with a radiation lesion]. PMID- 1441375 TI - [The treatment of patients with ischemic heart disease and significant disorder of left ventricular function]. AB - A study is presented of 71 patients with ischemic heart disease verified coronarographically and showing severe disorders of contractile function of the left ventricle. Thirty-eight patients who underwent the operation of aortocoronary shunting showed an improvement of the contractile capacity of the myocardium, and a longer survival as compared with those treated medically. Medical treatment was accompanied by more complications in the form of myocardial infarctions, cardiac insufficiency resulting often in a lethal outcome. PMID- 1441376 TI - [Cardiac contractile function in hypertension patients who have had a large-focus myocardial infarct]. PMID- 1441377 TI - [The procedure for the emergency treatment of patients with a heart rhythm and conduction disorder]. PMID- 1441378 TI - [Changes in heart volume in patients with iron-deficiency anemia (based on data from teleroentgenocardiography)]. AB - Teleroentgenocardiography was employed in 96 patients with iron deficiency anemia with the purpose of evaluating the cardiac volume. This volume increased with advance of the disease. The number of women with cardiomegaly increased as well. Cardiomegaly showed a tendency to normalization in the course of treatment. These findings are of importance for the treatment and rehabilitation of patients with iron deficiency anemia. PMID- 1441379 TI - [The late treatment results in patients with the irritable bowel syndrome]. PMID- 1441380 TI - [The detection of foci of tuberculous infection]. AB - Data from an antitubercular hospital in Krasnoyarsk Territory indicate that of 184 autopsy cases with pulmonary tuberculosis in 99 cases no official registration for tuberculosis has been noted and the patients were not treated for this disease. Four of these patients suffered of active forms of tuberculosis. PMID- 1441381 TI - [Secondary pneumonia in subjects with acute leukemia]. AB - Of 105 patients with acute leukoses secondary pneumonias were found in 47.6%. A dependence was found of the frequency of pneumonia on the severity of initial hyperleukocytosis and duration of post-cytostatic agranulocytosis. The efficiency of routine criteria of diagnosis was 66% and increased significantly in microbiological and cytological investigation of the bronchoalveolar lavage fluid. TREATMENT: combined antibacterial therapy, antifungal, desintoxicating agents; in severe cases--endobronchial administration of monogroup leucocytic mass. PMID- 1441382 TI - [Left ventricular function in patients with chronic obstructive bronchitis]. AB - A study of 45 patients with chronic obstructive bronchitis by the method of radionuclide ventriculography with 99mTc showed that even the early stages of the disease were characterized by an inhibition of the contractile function of the left cardiac ventricle. With progression of respiratory insufficiency, maintaining of the left cardiac ventricle stroke volume is achieved by increase of the final-diastolic and final-systolic volumes. Appearance of signs of cardiac decompensation is accompanied by a breakdown of this compensatory mechanism accompanied by a reduction of the strike volume and diminished rate of contraction of the circular fibers of the left ventricle myocardium. PMID- 1441383 TI - [The role of the immune and fibrinolytic systems in the inhibition of atherogenesis in chronic obstructive bronchitis]. AB - A study of the immune and fibrinolytic systems of the body in 216 patients with different clinical forms of atherosclerosis (exertion and rest stenocardia, arrhythmias, atherosclerotic hypertension), chronic obstructive bronchitis revealed that the antiatherogenous effect of chronic obstructive bronchitis is predetermined on the one side by an increased function of the monocytic macrophagal link of immunity and on the other by activation of the fibrinolysis system. PMID- 1441384 TI - [The immunomodulator kemantan in the treatment of patients with exacerbated chronic obstructive bronchitis]. PMID- 1441385 TI - [The prediction of the risk of an unfavorable outcome in bronchial asthma patients (based on anamnestic data)]. PMID- 1441386 TI - [Experience in organizing a rehabilitative care club for bronchial asthma patients]. PMID- 1441388 TI - [A validation of the pathogenetic treatment of alopecia areata]. PMID- 1441387 TI - [The activity of the metabolic processes in phagocytosing cells in sarcoidosis patients]. AB - A study of 109 patients with active sarcoidosis revealed an activation of the metabolic processes of phagocytes but with extension and duration of the disease they subside. Apparently, this is related to exhaustion of the functional capacities of the cells. Though, namely, low initial metabolic activity favours spreading and delay of the pathological process. PMID- 1441389 TI - [The use of bemitil in patients with progressive muscular dystrophies]. AB - Bemithyl treatment was carried out in 22 patients with neuromuscular diseases (progressive myodystrophy). The actoprotector bemithyl inhibited in these patients the processes of lipid peroxidation, activation of neoglucogenesis favours improvement of interorganic exchange of metabolites. Bemithyl is recommended in patients with progressive myodystrophy along with drugs normalizing the protein, energy and electrolyte metabolism. PMID- 1441390 TI - [Electrostimulation in the treatment of a facial nerve lesion]. AB - The author developed and introduced in the clinic a method of electric stimulation with sinusoidal modulated currents (using the "Amplipulse" device) in 114 patients with facial nerve lesions. A differentiated approach to electric stimulation is recommended in normal and reduced electric excitability of mimic muscles. PMID- 1441391 TI - [Nervous system involvement in Madelung's syndrome]. AB - Due to proliferation of the fatty tissue in the neck and depending on the degree of compression of the pharynx, larynx, vessels, nerve trunks the patients show, respiratory disorders, swallowing disturbances, dysarthria, stenocardia, neck and occipital pain, scalenus syndrome, cervicobrachialgia, posterior cervical sympathetic syndrome, disorders of the cerebral and spinal blood circulation. Involvement of both the central and peripheral nervous system are observed in Madelung's disease. PMID- 1441392 TI - [The tocopherol acetate and splenin correction of the immunological disorders in patients with viral hepatitis B]. AB - Inclusion of tocopherol acetate and splenin into complex treatment of viral hepatitis B (VHB) ensures a marked immunomodulating effect consisting in control of T-lymphopenia, normalization of helper-suppressor ratio, reduction of circulating immune complexes and a tendency to restoration of normal ratio between separate fractions of immune complexes, stimulation of phagocytic activity of monocytes of the peripheral blood. Splenin and tocopherol acetate are recommended in the complex treatment of hepatitis B. PMID- 1441393 TI - [The clinical significance of the sulfhydryl groups in the peripheral blood lymphocytes of patients with thyrotoxic goiter]. AB - A study of 42 patients with thyrotoxic goiter revealed a reduction of SH groups in the peripheral blood lymphocytes. The reduction depended on the severity of the pathological process. Changes of the SH groups are an informative criterion of the severity of the disease and treatment efficacy. PMID- 1441394 TI - [Rheoencephalography in assessing the cerebral hemodynamics in patients with euthyroid and toxic goiter]. PMID- 1441395 TI - [Infrared thermography in the diagnosis and assessment of treatment efficacy in patients with eczema nad allergic dermatitis]. AB - Thermography was used for examination of 45 patients with eczema and 18 patients with allergic dermatitis. Eczema patients without clinical improvement showed no positive thermographic picture. Thermography is of importance in the evaluation of treatment efficiency in patients with eczema and allergic dermatitis. PMID- 1441396 TI - [The late appearance of diagnostic titers of specific antibodies in patients with typhoid fever]. PMID- 1441397 TI - [Polyserositis as a complication of sarcoma of the heart]. PMID- 1441398 TI - [Ievhen Ozarkevych--one of the founders of Ukrainian medical science]. PMID- 1441399 TI - [The illness and last days in the life of Taras Hryhorovych Shevchenko]. PMID- 1441400 TI - [The acupuncture reflexotherapy of diabetes mellitus patients]. PMID- 1441401 TI - [Russian-Ukrainian medical dictionary. 7000 words]. PMID- 1441402 TI - [The function of the hypophyseal-thyroid system in the children of Zhitomir Province living in areas polluted by the radionuclides resulting from the accident at the Chernobyl Atomic Electric Power Station]. AB - A study of 1167 children (age: 7-15 years) inhabiting districts contaminated with radionuclide due to Chernobyl atomic station accident indicates that children with thyroid hyperplasia revealed high requirement and intensity of the peripheral metabolism of thyroid hormones that results finally in relative hormonal deficit (subclinical hypothyroidism) and thyroid hyperplasia. This is a sequel of maximum functional tension of the thyroid with impending breakdown of adaptation and this should be considered as a pathological process requiring correction, i.e. presence of subclinical hypothyroidism in children with thyroid hyperplasia requires substitution therapy with thyroid hormones. PMID- 1441403 TI - [The immune status of patients with neurocirculatory dystonia subjected to ionizing radiation exposure during the cleanup of the accident at the Chernobyl Atomic Electric Power Station]. AB - The immune state of 77 cleanup workers of Chernobyl power plant accident suffering from vegetative dystonia was studied. The group of comparison consisted of 10 vegetative dystonia patients, who were not subjected to the ionizing radiation influence. The workers showed no specific changes of immunity, but immune state disturbances among them were more frequent and more pronounced that in ordinary vegetative dystonia patients. PMID- 1441404 TI - [Sexual functions in men subjected to ionizing radiation exposure resulting from the accident at the Chernobyl Atomic Electric Power Station]. AB - A study of 426 males who participated in liquidating the sequels of the Chernobyl atomic station disaster revealed specific changes of the sexual active and generative function. Data are reported on the main mechanisms of these disorders and treatment results are analyzed. PMID- 1441405 TI - [The use of pectin-containing enterosorbents in exposure to radionuclides and heavy metals]. AB - The pectin-vitamin composition (PVC) and its complex with active carbon (AC) was investigated for use as an oral sorbent to protect radionuclide (Sr-85, Cs-137) accumulation. PVC is composed of the natural mixture of cellulose, pectin (Ca salt), flavonoides, vitamins of the B-group, PP and C. Investigation of PVC radioprotective action was carried out on the two groups of rats (n = 30) which received 1306 Bk/animal of Sr-85 or 343 Bk/animal of Cs-137 daily. One of the group of rats received every day also 300 mg of PVC. After 30 days level of Sr-85 was less by 56.6%, level of Cs = 137 was less by 27.6% in PVC-treated than in the control group (P < 0.05). Composite sorbent consisting of PVC and AC was slightly less effective in removing of Sr and Cs. PMID- 1441406 TI - [The hypertensive heart: its pathogenesis, diagnosis and treatment]. PMID- 1441407 TI - [Atypical attacks of stenocardia of effort occurring at rest]. AB - Results of a clinico-instrumental examination and treatment of 320 patients with ischemic heart disease revealed that 147 of them showed both exertion stenocardia and angina pectoris attacks in seemingly physical rest that could be considered as spontaneous stenocardia. An analysis of the clinical picture of the disease in these patients allowed to distinguish five atypical variants of effort stenocardia that imitated stenocardia during rest: hemodynamic, stenocardia during arterial pressure elevation, cardiac arrhythmia, vasospastic and night effort stenocardia attacks. A differential approach to to complex treatment of patients with the above forms of effort stenocardia is necessary. PMID- 1441408 TI - [Radionuclide methods for studying the central and regional hemodynamics of patients with dilated cardiomyopathy]. AB - Radiocardiography was used in 26 patients with dilated cardiomyopathy and in 20 practically healthy persons. Results revealed significant changes of the central and regional hemodynamics manifested in a reduction of the minute cardiac volume, delayed blood flow velocity, disorders of the cardioportal and cerebral hemodynamics. PMID- 1441409 TI - [The effect of combined treatment with the use of magnetotherapy on the systemic hemodynamics of patients with ischemic heart disease and spinal osteochondrosis]. AB - The authors examined 66 patients with ischemic heart disease and concomitant cervico-thoracic osteochondrosis and 22 patients without osteochondrosis. Differences were revealed in values of the systemic hemodynamics with prevalence of the hypokinetic type in patients with combined pathology. Inclusion of magnetotherapy in the treatment complex of patients with ischemic heart disease and osteochondrosis favours clinical improvement, normalization of indices of central and regional blood circulation. PMID- 1441410 TI - [The effect of compensatory mechanisms of pancreatic exocrine function on the course and outcome of rehabilitative treatment in patients with chronic primary gastroduodenitis]. AB - Methods of endogenous stimulation of the exocrinous pancreatic function in chronic primary gastroduodenitis were used. It was expressed in parallel gastric hyperchlorhydria, hyperproduction of pancreatic hydrocarbonates at initial stages of chronic primary gastroduodenitis and reduction of their excretion with diverse changes of the activity of pancreatic enzymes in prolonged and persistent course of the disease. PMID- 1441411 TI - [The results of using a mathematical method for the differential diagnosis of pulmonary tuberculosis and cancer]. AB - The authors developed a table differential-diagnostic algorithm designed for improvement of the differential diagnosis of pulmonary tuberculosis and cancer. This algorithm allows to establish precise diagnosis of cancer or tuberculosis of the lungs at district and regional health service levels, enhances the time of diagnosis and favours rational treatment. PMID- 1441412 TI - [The diagnosis of acute pneumonia in respiratory viral infections]. AB - Data are reported of 582 case records of patients with acute pneumonia of different influenza epidemic periods, results of a study of 175 lethal cases due to acute pneumonia, that complicated influenza in adults as well as experimental studies on reproduction of para-influenzal-staphylococcal, influenzal-Klebsiella and Proteus-influenzal infections. The study allowed to find out the causes of diagnostic difficulties, to establish the features of the course of acute pneumonia in patients with respiratory viral diseases to disclose the mechanisms of development of lung changes and make propositions facilitating early clinical diagnosis on the prehospital period. PMID- 1441413 TI - [Lipid peroxidation following ultraviolet irradiation of the blood and the protective action of tocopherol acetate (experimental research)]. AB - Original experimental data are reported on processes occurring in the blood after UV irradiation. A study of the content of primary and secondary products of lipid peroxidation, vitamin E and the resistance of erythrocytes to hemolysis, catalase activity before and after UV irradiation of animals of different age groups revealed that UV irradiation of the blood changes not only the intensity of the process of lipid peroxidation but also the direction of metabolism of unsaturated fatty acids in the blood cells, exchange of semiproducts between them and the plasma, but also weakens the antioxidant systems of the blood. These processes are age-dependent. Preliminary administration of vitamin E preparations secures a high antioxidant homeostasis in the blood, especially after UV irradiation. PMID- 1441414 TI - [The biochemical criteria for evaluating the early signs of the adverse action of nitrochlorobenzine compounds]. PMID- 1441415 TI - [Ethonium in the treatment of peptic ulcer patients]. AB - Results are reported of clinical trials in 52 patients of ethonium belonging to quaternary ammonia compounds with consideration of the patients' age and concomitant disorders of the hepatobiliary system. It was established that ethonium possesses a marked antiradical and antioxidant effect in ulcer disease, furthering potentiation of the activity of peroxidedysmutase, protective enzymes of the glutathione system, improvement of bioenergetic processes in the gastric mucosa, enhancement of ulcer healing, prevention of ulcer recurrence. PMID- 1441416 TI - [The intensive therapy of young patients with acute pneumonia]. PMID- 1441417 TI - [The clinical characteristics of a cerebral ischemic stroke with a tumor-like course]. AB - A complex examination (clinical picture, EEG, REG, EchoEG, CT, angiography) of 27 patients with ischemic stroke showing a tumour-like course allowed to single out three variations of stroke course: with a stormy development of the disease due to the hypertensive syndrome; with a remittent course; with epileptic seizures and absence in the postseizure period. The character and frequency of the above variants of the onset and further clinical course of cerebrovascular insufficiency will favour early diagnosis and efficient treatment of the disease. PMID- 1441418 TI - [Endoscopic retrograde cholangiopancreatography in the diagnosis of pancreatic diseases]. AB - Additional criteria for endoscopic cholangiopancreatography are evaluated: endoscopy data, passage of the contrast medium, subjective symptomatology. A study of 271 patients with clinical data of involvement of the pancreas was carried out. The obtained data widen the possibilities of this method, especially in the diagnosis of chronic pancreatitis. PMID- 1441419 TI - [The characteristics of the clinical picture of candidiasis of the skin and mucous membranes in patients with chronic dermatosis]. AB - The author describes the clinical picture and course of candida infection of the skin and mucous membranes in 176 patients with chronic dermatoses (eczema, atopic dermatitis, psoriasis). Several patients (9%) showed torpid, atypical manifestations of candidosis, often masqueraded by other skin pathology. It was established that Candida infection is one of the causes of long-term, torpid course and increase of number of recurrences of the main dermatosis, development of a polymorphous clinical picture and mycogenous sensibilization. There was also a reverse relationship: chronization of the Candida process and prolonged elimination of the pathogen, insufficient efficacy of anticandidosis treatment. This dictates the necessity of detailed examination of patients with chronic dermatoses and mycological check-up with the purpose of modern diagnosis and treatment of candidosis of the skin and mucous membranes. PMID- 1441420 TI - [The prevalence and secondary prevention of ischemic heart disease and arterial hypertension in workers of the gas recovery industry]. AB - Results are reported of the incidence of ischemic heart disease and arterial hypertension in workers of the gas producing industry. There was a direct correlative dependence on age, profession, character of work. Schemes are presented on the treatment with consideration of the course of the disease. PMID- 1441421 TI - [The prevention of occupational diseases in glassware grinders]. AB - The role is shown of a complex of hygienic measures in the prophylaxis of professional diseases of the hands of grinders--reduction of the level of morbidity and delay of the onset of symptoms. Nonobedience of hygienic regulations is the major cause of failures of prophylactic measures. The authors worked out physiological regulations of static loads and effective means of their control. PMID- 1441422 TI - [The content of manganese in the hair as a test of exposure in welders]. PMID- 1441423 TI - [The spiritual revival of Ukrainian medicine]. PMID- 1441424 TI - [Experience with the secondary prevention of noninfectious diseases under the new economic mechanism]. PMID- 1441425 TI - [The Department of Phthisiatrics with a course in pulmonology on the 150th anniversary of the Kiev Medical Institute]. PMID- 1441426 TI - [The activities of I. A. Sikorskii as a neurologist]. PMID- 1441427 TI - [The phenomenon of antigenic defectiveness in naturally circulating strains of the tick-borne encephalitis virus and its possible connection to seronegative forms of the disease]. AB - Ten strains of tick-borne encephalitis (TBE) virus isolated from single specimens of I. persulcatus ticks were studied. The strains were divided into antigenically complete (AC) and antigenically defective (AD), depending on the presence or absence of some virus antigens in concentrated virus preparations, characteristics in rocket immune electrophoresis (RIEP), rate and intensity of humoral immune response in monkeys and rabbits, and plaque size in SPEV cell culture. The AC-strain markers include high activities of precipitating, hemagglutinating (HA), and complement-fixing (CF) antigens, formation of precipitates moving in rocket shape towards anode and cathode in RIEP, rapid development of antihemagglutinins and virus-neutralizing antibodies, large plaques (3-5 mm). The AD variants are characterized by the lack of HA and precipitating activity, low titres of CF antigen, slow and poor immune response, the lack of cathode precipitate "rocket", very small plaques. The antigenic defectiveness is transitory and shows in early passages; after 10-11 passages in SPEV cell cultures or in white mice, transformation AD----AC occurs. A transformed strain is neutralized, like standard TBE strains, by blood sera of a typical patient with poliomyelitis-like form of TBE. Examinations of blood sera from the population of an endemic zone (Yaroslavl Province) and 67 TBE patients (Kurgan Province) demonstrated the association of AC and AD variants with the formation of immune portion of the population and TBE etiology. Cases of the disease confirmed by seroconversion in HI with commercial diagnosticum are associated with AC variants, whereas AD variants are associated with those TBE cases which are difficult to diagnose using the commercial diagnosticum. PMID- 1441428 TI - [A trial of the intranasal vaccination of adults against measles: the approaches to an alternative revaccination method]. AB - The safety and efficacy of a measles vaccine from the L-16 strain was studied after its intranasal administration to adult volunteers using an atomizer. The controls were adult volunteers given one dose of the vaccine subcutaneously. The measles vaccine given intranasally was used in the same or double dose. The intranasal administration of the vaccine caused practically no side effects. Within 14-60 days postvaccination, the volunteers in all the groups showed a significant rise in titres of antibodies to measles virus determined by hemagglutination inhibition test. The double dose of intranasally administered vaccine was approximately as effective as a single dose given subcutaneously. PMID- 1441429 TI - [Yucaipa-like viruses isolated in Kazakhstan in 1987-1989]. AB - From domestic birds 13 strains of avian paramyxoviruses, serotype 1, and 14 strains of serotype 2 were isolated. Avian paramyxoviruses, serotype 2, differ antigenically and biologically from each other and from the prototype variant chicken/Yucaipa/California/56. The virus was also detected experimentally in birds having contact with the infected specimens. Examinations of avian blood sera revealed wide dissemination of viruses related to the chicken/Yucaipa/56 strain in domestic bird breeding farms (43.6% to 50.0% of positive birds). The detected variability of the antigenic structure of the isolates attests to the potential emergence of a pathogenic variant. PMID- 1441430 TI - [The etiology of chronic anti-HBc-positive hepatitis]. PMID- 1441431 TI - [The principles for standardizing serum panels intended for the quality assessment of diagnostic test systems (exemplified by an immunoenzyme test system for detecting HIV antibodies)]. PMID- 1441432 TI - [The quantitative detection of orthopoxvirus antibodies in studying sera in a single dilution in an immunoenzyme test system with a conjugate of protein A and peroxidase]. PMID- 1441433 TI - [The enhancement of the diagnostic reliability of immunoblot for HIV-1 antibodies by enriching the preparation for immunoblot with the HIV-1 gp120 protein]. AB - The diagnostic value of original immunoblot system depends on the availability of enveloped protein GP120 because it is the antibodies to this polypeptide that frequently indicate the running virus infection. This polypeptide is lost during purification of viral material but remains free in culture medium. The extraction of GP120 from culture fluid with immunosorbent based on sepharose 4B with ligated immunoglobulins from HIV-1-infected persons enriched the preparation for immunoblot with proteins increasing its diagnostic value. PMID- 1441434 TI - [The inhibiting action of interferon inducers on the multiplication of the human immunodeficiency virus]. AB - High molecular natural (ridostin and larifan) and synthetic (camedon) interferon inducers inhibited HIV-1 replication in MT-4 and CEM cultures when administered simultaneously with the inoculum. The effect of interferon inducers was comparable with that of azidothymidine in concentrations providing cell protection. The degree of culture protection determined by the number of viable and antigen-containing cells was approximately similar for strain 899A and freshly isolated IV39. No significant difference in the efficacy of the preparations in the two different cell cultures. MT-4 and CEM, was observed. It may be assumed that the antiviral effect of the interferon inducers under study will depend little on the type of cell culture. PMID- 1441435 TI - [The use of DNA polymerase from Thermus thermophilus]. AB - National DNA polymerase from Thermus thermophilus was used in polymerase chain reaction (PCR). The synthetic oligonucleotides (primers) to the basic structural HIV genes GAG, ENV, the genome DNA of donor peripheral blood lymphocytes were used, and the controls included the plasmid DNA with cloned HIV genome and the genome DNA of peripheral blood lymphocytes from HIV-infected persons confirmed by ELISA and Western blot analysis. The PCR technique and evaluation of the obtained results are described. The expediency of using PCR for different contingents is discussed. PMID- 1441436 TI - [The use of a virazole aerosol in young children with a respiratory syncytial virus infection]. AB - The therapeutic effect of aerosol virasol was studied in young infants suffering from RS virus infection with concomitant broncho-obstructive syndrome. The study involved 60 children between 1 month and 4 years of age of whom 30 were treated with virasol and another 30 made a control group. Virasol was shown to reduce the severity of the clinical picture to a considerable degree and speed up the recovery in infants with RS virus disease. Virasol is recommended for inhalation treatment of infants with RS virus infection and concomitant broncho-obstructive syndrome. The daily dose of virasol is 10 mg per kilo of body weight. The duration of one course is 3 to 5 days. PMID- 1441437 TI - [The origin of pandemic strains of the influenza A virus]. PMID- 1441438 TI - [The detection and quantitative determination of antigens to the human immunodeficiency virus types 1 and 2]. AB - Three modifications of ELISA test system for HIV antigen detection are described. They are based on IgG from HIV-1 and HIV-2-infected human sera and monoclonal antibodies against HIV-1 p24 used as immunosorbents. The peroxidase/anti-HIV-IgG conjugate was used in all the test systems. A possibility of quantitative detection of viral antigen in native culture fluids, lysates, and purified virus preparations was demonstrated. The test system for HIV-1 antigen detection cannot be used for HIV-2 antigen detection and vice versa. The diagnostic value of HIV-1 p24 antigen detection consists in the possibility of earlier AIDS identification and monitoring of the disease at various stages. The sensitivity of "p24" assay is 0.5 ng/ml. PMID- 1441439 TI - [Monoclonal antibodies to the influenza A virus matrix protein that react with viral strains of different subtypes]. AB - To obtain hybridomas secreting monoclonal antibodies (MCA) to matrix (M) protein of influenza virus, mice were immunized with a modified antigen which consisted of subvirus units after electrophoretic removal of surface glycoproteins from virions using Desintegnon-O detergent. Six stable hybrid cultures producing MCA to M-protein were derived. The properties of MCA to the antigen determinant common for a group of influenza A virus strains of different subtypes allow them to be used in the development of a test-system for diagnosis of influenza A type. PMID- 1441440 TI - [The characteristics of the humoral response to respiratory syncytial viral infection in adult patients with different forms of bronchitis]. AB - The levels of specific IgG and IgM were determined in 72 patients with verified respiratory syncytial (RS) virus infection: 11 patients with acute delayed bronchitis (ADB), 26 with recurring bronchitis (RB) 35 with chronic obstructive bronchitis (ChOB), by indirect enzyme immunoassay; RS virus was detected by direct immunofluorescent technique. The activity of the inflammatory process in the bronchi was shown to depend upon RS infection activity in cases of ChOB and RB. RS infection was observed to be significantly dependent on obstruction and bronchospasms. The specific humoral response was reduced and delayed in ChOB and RB as compared to acute bronchitis. The possibility of long-term persistence of RS virus antigen in chronic and recurring forms of bronchitis was demonstrated. PMID- 1441441 TI - [The interrelationship of the causative agents of subacute transmissible spongiform encephalopathies]. AB - Virological, histological, and electron microscopy methods were used to study the features of the infectious process in minks infected with scrapie agent as compared with that in minks infected with the agent of mink transmissive encephalopathy and in mice infected with scrapie. The results of the study showed the similarity in the clinical picture and the pattern of histological and ultramicroscopic lesions in minks infected with either of the agents. On the basis of the authors' own data and those from the literature, the relationship among the agents of the diseases comprising the group of subacute transmissive spongiform encephalopathies is discussed. PMID- 1441442 TI - [The effect of the methods for producing an experimental Marburg virus infection on the characteristics of the course of the disease in green monkeys]. AB - A comparative study on the features of the pathogenesis of Marburg disease after parenteral and aerosol infection of green monkeys with a virus prepared from native culture suspension and that after lyophilization was carried out. The changes in the dynamics of the clotting time, the activity of serum aminotransferases, the duration of prefebrile period and survival time were analysed in different cases. No lethality was observed in animals infected with small doses of aerosol preparations. PMID- 1441443 TI - [Changes in the blood serum aminotransferase activity in the experimental infection of Cercopithecus aethiops monkeys with the Marburg virus]. AB - Aminotransferase levels in the peripheral blood serum of African green monkeys were studied after aerosol infection with lyophilized virus preparation. A correlation between aminotransferase activity and other symptoms of hemorrhagic fever was shown. Considerable variations in the features of aminotransferase activity in severe and mild cases of the disease were observed. PMID- 1441444 TI - [Polypeptides p14 and p31 of the African swine fever virus--early proteins located on the membrane of the infected cell]. AB - African swine fever virus polypeptides p14 and p31 are synthesized in the presence of phosphonacetic acid which inhibits viral DNA replication, and therefore they are early viral proteins. These polypeptides were found to be localized on plasma membranes by immunofluorescence with monospecific antisera and monoclonal antibodies and by selective solubilization of infected cells. The p14-specific antibodies mediate complement-dependent cytolysis and antibody dependent cytotoxicity of the cells infected with African swine fever virus. PMID- 1441445 TI - [Immune reactions to the African swine fever virus]. AB - Host immune reactions to African swine fever virus variants differing in their virulence were studied comparatively. Their obvious variabilities in antibody induction to some polypeptides active in antibody-dependent cell cytotoxicity and cytotoxic T-lymphocytes were demonstrated. T-helpers of immune pig splenocytes were found to recognize the cells infected with avirulent but not virulent virus variants. The described differences were not connected with the changes in SLA-1 antigen expression in the infected cells but correlated with induction of host resistance, chronic or acute course of the disease with fatal outcome. PMID- 1441446 TI - [The effect of the influenza virus on the activity of macrophage 5-nucleotidase and murine resistance to staphylococcal infection]. PMID- 1441447 TI - [The genome of the measles virus in the peripheral blood lymphocytes in kidney diseases]. PMID- 1441448 TI - [A method for the hydrophobization of antibodies leading to an enhancement of the sensitivity of an immunoenzyme analytical test system for detecting HBsAg]. PMID- 1441449 TI - Radical vulvectomy--a 21-year review. AB - The factors surrounding patients subjected to radical vulvectomy were examined. Most patients were over the age of 40 years. The standard butterfly incision was used in all but 2 cases. The histology in all cases was invasive squamous cell carcinoma. The main complications were primary haemorrhage, urinary tract infection and wound dehiscence. The mean hospital stay was 50 days and the mortality rate was 4 per cent. PMID- 1441450 TI - Cancer in the Caribbean and environs. A comparison of age-standardized rates for 9 population groups. AB - Age-standardized rates for cancer in Kingston & St. Andrew, Jamaica are presented by site and sex, and compared with data from Registries in the Caribbean and adjacent regions. These comprise Costa Rica, Cuba, Cali (Colombia), Martinique, the Netherlands Antilles (excluding Aruba), New Orleans (Whites and Blacks) and Puerto Rico. There are significant differences which demand explanation. Overall, the reported rates are highest in New Orleans, which leads in breast cancer, tumours of bronchus, larynx, colon, rectum, pancreas, prostate and bladder. Lymphomas occur most frequently in Whites in New Orleans while Blacks in that city show similar rates to other Registries in the area. Cali (Colombia) and Costa Rica lead in cervical cancer, with Jamaica third. The lowest figure is for Whites in New Orleans. Cali (Colombia) and Costa Rica also have very high rates for gastric cancer, and low rates for colonic. Oesophageal cancer is highest in Blacks in New Orleans, followed by Martinique and the Netherlands Antilles. Jamaica has shown a steady decline for this site over 30 years. The rate in Whites in New Orleans is only one-fourth of that in Blacks. PMID- 1441451 TI - Mesolimbic deficits exacerbate amphetamine treatment. Clinical implications for drug abusers. AB - Amphetamine, a common drug used by abusers, is able to produce a schizophreniform psychosis in man. The experiment reported here examined amphetamine in relation to its role in the nucleus accumbens septi (NAS) and the globus pallidus. The effects produced by apomorphine, a direct dopamine (DA) agonist, were compared with those of amphetamine, a known indirect DA agonist. The data revealed that amphetamine in NAS-lesioned animals produced very active stereotypy which intensified with time. This effect was blocked by pallidal lesioning. Apomorphine in pallidectomised rats produced persistent stereotypy, but of diminished intensity. The results are discussed in terms of the mediating roles of the NAS and globus pallidus on behavioural sequelae. PMID- 1441452 TI - Primary repair of the cholecyst-enteric fistula in gallstone ileus. AB - Gallstone ileus is a rare cause of mechanical bowel obstruction. The attendant lack of awareness by the clinician will not only result in the diagnosis being made intraoperatively but will also affect the adequacy of the preoperative preparation of these ill patients. These patients are often elderly, septic and have significant concomitant medical illnesses. Recently two patients with gallstones ileus were managed with enterolithotomy and primary repair of the cholecyst-duodenal fistula at the University Hospital of the West Indies, Jamaica. Their clinical presentations and progress are described along with a review of the classical clinical course, radiological features, and operative choices available. PMID- 1441453 TI - Acute acalculous cholecystitis. AB - Acute acalculous cholecystitis is now well recognised but is almost certainly not an homogeneous entity. The recognition of at least two sub-groups would appear to enhance the clinical perspective of this problem and facilitate on-going study and discussion. Two cases representing one of these sub-sets are reported, and both varieties are described. PMID- 1441454 TI - Colo-mucosal proctectomy with ileo-anal anastomosis. The Jamaican experience. AB - A total colectomy and a mucosal proctectomy with ileo-anal anastomosis (c-mp-iaa) effectively removes all debilitating, potentially malignant colonic mucosa. Preservation of the anorectal sphincter predictably results in good to excellent anal continence with a low mortality and acceptable morbidity. Since 1983 at the University Hospital of the West Indies (U.H.W.I.), Jamaica, five (5) patients have undergone c-mp-iaa for colonic mucosal disease. All have good to excellent anal continence with an average of 2-6 continent, formed stools per day. There were no operative deaths. The five (5) cases are described and a plea is made for the earlier use of this definitive surgical procedure where indicated. PMID- 1441455 TI - Immunohistochemistry of lymphocyte B-cell lymphoma of the prostate gland. AB - A case of small lymphocytic B-cell lymphoma occurring in the prostate gland of a 68-year-old man is reported. These tumours are rarely encountered in surgical specimens, and may be confused with an undifferentiated carcinoma. Differentiation is readily made, using immunohistochemical techniques. PMID- 1441456 TI - Bothrops atrox snake bite in a six-year-old child. AB - A rare case of snake bite poisoning presenting as disseminated intravascular coagulation is presented. It is important to consider this entity in the differential diagnosis of children presenting with acute bleeding disorders in the West Indian islands where Bothrops atrox is present, namely, in Trinidad, St. Lucia and Martinique. PMID- 1441457 TI - Professional etiquette. PMID- 1441458 TI - Acute infectious diarrhoea in adults. PMID- 1441459 TI - Cimetidine. Potential for its use in HIV disease. PMID- 1441460 TI - Biliary surgery in patients with sickle-cell anaemia. AB - The results of biliary surgery are reported in 12 consecutive patients with homozygous sickle-cell (SS) disease treated over a two-year period at the University Hospital of the West Indies, Kingston, Jamaica. Recommendations for the surgical management of these patients are outlined. PMID- 1441461 TI - Pregnancy outcome in paraplegic women. AB - Six cases of paraplegia in pregnancy are reviewed. The major medical complications were urinary tract infection and anaemia. The obstetrical problems were pre-term labour and one perinatal loss due to unattended birth. PMID- 1441462 TI - Physician-patient sexual contact. Prevalence and problems. AB - To document the current prevalence of physician-patient sexual contact and to estimate its effect on involved patients, 10,000 family practitioners, internists, obstetrician-gynecologists, and surgeons were surveyed. Of the 1,891 respondents, 9% acknowledged sexual contact with 1 or more patients. Even in the unlikely case that none of the nonrespondents had sexual contact with patients, its prevalence among all 10,000 physicians surveyed would still be 2%. Of respondents, 23% had at least 1 patient who reported sexual contact with another physician; 63% thought this contact was "always harmful" to the patients. Almost all (94%) responding physicians opposed sexual contact with current patients; 37% also opposed sexual contact with former patients. More than half of respondents (56%) indicated that physician-patient sexual contact had never been addressed in their training; only 3% had participated in a continuing education course focusing on this issue. Clear and enforceable medical ethics codes concerning physician-patient sexual contact are needed, as well as preventive educational programs for medical schools and residency programs. PMID- 1441464 TI - Quantitative quality assurance in a community hospital pediatric intensive care unit. AB - Unbiased, objective evaluations of quality of care are preferred over subjective evaluations. We observed 681 admissions to a pediatric intensive care unit of a community hospital from 1989 through 1990 for outcomes and physiologic profiles of the patients on the admission day using the Pediatric Risk of Mortality score to assess severity of illness. Mortality adjusted for severity of illness was compared with that predicted from a pediatric intensive care unit of a tertiary medical center: 32.6 deaths were predicted based on the physiologic profiles, and 23 occurred. The number of outcomes and their distribution according to mortality risk indicated close agreement between observed and predicted results. Thus, a quality-assurance technique developed in tertiary care centers can be used to indicate a comparable level of care in a community hospital. PMID- 1441463 TI - Mycobacterium avium complex and Mycobacterium tuberculosis in patients infected with the human immunodeficiency virus. AB - Primary care physicians play an important role in identifying and treating bacterial infections in adults infected with the human immunodeficiency virus (HIV). Mycobacterium avium complex and Mycobacterium tuberculosis are pathogens that can cause systemic or local infection in these patients. We review the epidemiology, pathogenesis, clinical presentation, and principles of treatment for these two mycobacterial pathogens. Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival. PMID- 1441465 TI - Screening mammography reports. Toward clear, concise clinical descriptions. PMID- 1441468 TI - Occupational asthma. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in chest diseases. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in chest diseases 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 Chest Diseases of the California Medical Association, and the summaries were prepared under its direction. PMID- 1441466 TI - Erythropoietin therapy in patients with chronic renal failure. AB - Symptomatic anemia is a common complication of chronic renal failure. Treatment is now possible with the availability of recombinant human erythropoietin (epoetin alfa). Previous experimental studies have suggested that correcting the anemia of chronic renal failure may be harmful in that renal failure may be accelerated. Although experience with this drug has been primarily restricted to its use in patients with end-stage renal disease, several recent trials have been reported in patients with varying degrees of chronic renal failure. We review these studies with particular reference to the progression of renal failure and the drug's reported side effects. We conclude that the use of epoetin is beneficial and well tolerated and that there is no compelling evidence for the acceleration of renal failure associated with its use in patients. PMID- 1441469 TI - Antibiotics for pneumonia. PMID- 1441470 TI - Diagnosis of pulmonary embolism. PMID- 1441467 TI - The second century of the antibody. Molecular perspectives in regulation, pathophysiology, and therapeutic applications. AB - The modern age of immunology began in 1890 with the discovery of antibodies as a major component of protective immunity. The 2nd century of the antibody begins with a focus on the molecular physiology and pathophysiology of immunoglobulin production. Numerous human variable-region antibody genes have been identified through advances in molecular cloning and anti-variable-region monoclonal antibodies. Some of these variable-region genes are now known to be involved in specific stages of B-lymphocyte differentiation and immune development. This connection has yielded new insights into the pathogenesis of immune dyscrasias and lymphoid neoplasia; common variable immunodeficiency and cryoglobulinemia are highlighted here. The molecular regulation of immunoglobulin expression suggests new targets for pathogenesis and clinical intervention. Finally, genetically engineered antibodies offer novel opportunities for diagnostic and therapeutic applications. PMID- 1441471 TI - Thrombolytic treatment of pulmonary embolism. PMID- 1441472 TI - Lung-assist devices. PMID- 1441473 TI - Bronchiolitis obliterans organizing pneumonia. PMID- 1441474 TI - Advances in pulmonary biopsy techniques. PMID- 1441475 TI - Lung transplantation. PMID- 1441476 TI - Monoclonal therapy for bacteremia and sepsis. PMID- 1441477 TI - Conventional treatment of cystic fibrosis. PMID- 1441478 TI - Aerosolized bronchodilators. PMID- 1441479 TI - Screening for obstructive sleep apnea using pulse oximetry. PMID- 1441480 TI - Long-standing latent idiopathic hypoparathyroidism discovered during concurrent central nervous system disease. PMID- 1441481 TI - Cerebral infarction as a remote complication of childhood Haemophilus influenzae meningitis. PMID- 1441482 TI - Ehrlichiosis in a visitor to Virginia. PMID- 1441483 TI - Blood-saturated operating-room shoe covers. PMID- 1441484 TI - The 'R' word. 'Rationing' of health care and the role of academic health centers. PMID- 1441485 TI - Physician aid in dying. What physicians say, what patients say. PMID- 1441486 TI - Assisted suicide--what euthanasia activists say, what people with disabilities say. PMID- 1441487 TI - The popular movement for physician-assisted dying--what the public is saying, what physicians are hearing. PMID- 1441488 TI - Death, politics, and philosophy. PMID- 1441489 TI - Physician aid in dying--finding the middle ground. PMID- 1441490 TI - Recombinant erythropoietin therapy in renal and nonrenal anemia. PMID- 1441491 TI - Manifestations of adult varicella in the United States Navy, 1984-1987. PMID- 1441492 TI - Successful treatment of markedly symptomatic patients with type II diabetes mellitus using high doses of sulfonylurea agents. PMID- 1441493 TI - Abdominal aortic aneurysm. Incidence in a hospital population at risk. AB - The incidence of abdominal aortic aneurysms has been studied in various selected patient groups. In this study, 100 male patients on a cardiology service who were older than 60 years and over 170 cm (5 ft 7 in) tall were examined by abdominal ultrasonograms. A total of 11 aneurysms were found, 2 of which were more than 4.5 cm in diameter. Other abnormalities that were found included renal disease in 20 patients (1 carcinoma treated with a curative nephrectomy), gallbladder disease in 22 patients, and miscellaneous intra-abdominal disease in 6 patients; 47 patients had no abnormalities found. The aneurysms of these patients were classified by a patient's height in 5-cm (2-in) increments. No significant difference in the incidence of aneurysms was found within the groups, but these groups are small and a significant difference would not be expected. It is of interest that the two large aneurysms were in persons taller than 180 cm (5 ft 11 in). Previous ultrasonographic studies of aneurysmal incidence have not reported other intra-abdominal disease. PMID- 1441494 TI - Radiation retinopathy. AB - Radiation therapy is effective against many cancerous and noncancerous disease processes. As with other therapeutics, side effects must be anticipated, recognized, and managed appropriately. Radiation retinopathy is a vision threatening complication of ocular, orbital, periorbital, facial, nasopharyngeal, and cranial irradiation. Factors that appear important in the pathogenesis of radiation retinopathy include total radiation dosage, fraction size, concomitant chemotherapy, and preexisting vascular disorders. Clinical manifestations of the disorder include macular edema and nonproliferative and proliferative retinopathy, similar to changes seen in diabetic retinopathy. Argon laser photocoagulation has proved efficacious for managing macular edema and fibrovascular proliferation in some of these patients. Ongoing basic laboratory and clinical research efforts have led to a better understanding of the pathogenesis, natural history, and treatment response of radiation retinopathy. The ultimate goal of this knowledge is to improve the prevention, recognition, and management of this vision-threatening complication. PMID- 1441495 TI - Effects of the multiple risk factor intervention trial smoking cessation program on pulmonary function. A randomized controlled trial. AB - To determine whether the decline in pulmonary function in smokers is modified by stop-smoking intervention, a randomized controlled study (the Multiple Risk Factor Intervention Trial) was done comparing participants in a special intervention group that included an intensive smoking cessation program with those assigned to usual care. The subjects were 6,347 middle-aged male smokers who had serial measurements of pulmonary function--principally the forced expiratory volume in 1 second (FEV1)--during 6 to 7 years of follow-up. No overall differences were detected in the rate of loss of FEV1 in the two groups. The use of beta-blockers, which had detrimental effects on FEV1, was significantly more common in the intervention group. Among nonusers of beta blockers, heavy smokers lost FEV1 at a rate about 11 ml per year slower in the intervention group than in the control group (2P = .09) and ended the trial with an FEV1 about 90 ml higher (2P = .05). These results support the inference from observational studies that smoking cessation has a beneficial effect on pulmonary function in heavy smokers. PMID- 1441498 TI - Transesophageal echocardiography. AB - The Council on Scientific Affairs of the California Medical Association presents the following inventory of items of progress in anesthesiology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, and scholars to stay abreast of these items of progress in anesthesiology, 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 Anesthesiology of the California Medical Association, and the summaries were prepared under its direction. PMID- 1441496 TI - Wake up and smell the coffee. Caffeine, coffee, and the medical consequences. AB - Caffeine is a methylxanthine whose primary biologic effect is antagonism of the adenosine receptor. Its presence in coffee, tea, soda beverages, chocolate, and many prescription and over-the-counter drugs makes it the most commonly consumed stimulant drug. Initially caffeine increases blood pressure, plasma catecholamine levels, plasma renin activity, serum free fatty acid levels, urine production, and gastric acid secretion. Its long-term effects have been more difficult to substantiate. Most of the caffeine consumed in the United States is in coffee, which contains many other chemicals that may have other biologic actions. The consumption of coffee is a self-reinforcing behavior, and caffeine dependence and addiction are common. Coffee and caffeine intake have been linked to many illnesses, but definitive correlations have been difficult to substantiate. Initial trials showing coffee's association with coronary disease and myocardial infarction have been difficult to reproduce and have many confounding variables. Recent studies showing a larger effect over long follow-up periods and with heavy coffee consumption have again brought the question of the role of coffee in disease states to the fore. Caffeine in average dosages does not seem to increase the risk of arrhythmia. At present there is no convincing evidence that caffeine or coffee consumption increases the risk for any solid tumor. The intake of coffee and caffeine has clearly been decreasing in this country over the past two decades, largely brought about by the increasing health consciousness of Americans. Although there have been many studies that hint that the fears of increased disease with coffee drinking may be warranted, many questions have yet to be answered about the health effects of coffee and caffeine use. PMID- 1441497 TI - Urinary tract infections in children. An update. AB - Urinary tract infection is a common and frequently recurring condition in children. The susceptibility of the host, the presence of urinary tract abnormalities, and the virulence of the urinary pathogens are of primary importance in the development of the infection. Renal parenchymal scarring, hypertension, and renal insufficiency are well-established complications of the infection in children. To reduce the risk of renal damage, diagnosis and treatment must be prompt. The diagnosis demands radiologic evaluation of the urinary tract in all boys, all children younger than 5 years, all patients with voiding dysfunction, and school-aged girls with recurrent infection to identify those patients with vesicoureteral reflux, obstruction, or other urinary tract abnormalities. Both voiding cystourethrography and renal ultrasonography are the initial examinations to use to determine the next appropriate study. Children with vesicoureteral reflux or with recurrent urinary tract infections should receive prophylactic antibiotic therapy and should be observed closely to prevent renal scarring. PMID- 1441499 TI - New applications of propofol. PMID- 1441500 TI - 'Do-not-resuscitate' orders in operating rooms. PMID- 1441501 TI - Novel approaches to the treatment of neuropathic pain. PMID- 1441502 TI - Postoperative pain. PMID- 1441503 TI - Perioperative myocardial ischemia. PMID- 1441504 TI - Sedating patients in intensive care units. PMID- 1441505 TI - Perioperative temperature control. PMID- 1441506 TI - Postoperative apnea syndrome in premature infants. PMID- 1441507 TI - Autologous blood transfusion therapy. PMID- 1441508 TI - Diffuse demyelinating lesions of the brain after the rapid development of hypernatremia. PMID- 1441509 TI - Adult Still's disease presenting as fever of undetermined origin in a patient with leukemoid reaction. PMID- 1441510 TI - Costs and coverage. Pressures toward health care reform. AB - Signs of discontent with the health care system are growing. Calls for health care reform are largely motivated by the continued increase in health care costs and the large number of people without adequate health insurance. For the past 20 years, health care spending has risen at rates higher than the gross national product. As many as 35 million people are without health insurance. As proposals for health care reform are developed, it is useful to understand the roots of the cost problem. Causes of spiraling health care costs include "market failure" in the health care market, expansion in technology, excessive administrative costs, unnecessary care and defensive medicine, increased patient complexity, excess capacity within the health care system, and low productivity. Attempts to control costs, by the federal government for the Medicare program and then by the private sector, have to date been mostly unsuccessful. New proposals for health care reform are proliferating, and important changes in the health care system are likely. PMID- 1441511 TI - Health care reform--another view. PMID- 1441512 TI - Getting some breathing room--persuading patients to stop smoking. PMID- 1441513 TI - Caffeine under examination--a passing grade. PMID- 1441514 TI - Urinary tract infections--navigating complex currents. PMID- 1441515 TI - Osmotic shifts, metabolic compromise, and the vulnerability of the pons. PMID- 1441516 TI - Blood-saturated shoe covers. PMID- 1441517 TI - Earthquakes and the practicing physician. PMID- 1441518 TI - Let's not do with euthanasia what we did with abortion. PMID- 1441519 TI - [Results of conventional treatment of severe congestive heart failure with vasodilators]. AB - In 61 patients with NYHA IV class chronic congestive heart failure, treated in succession with digoxin (D) and furosemide (F) for two weeks, with D+F and isosorbide dinitrate (S) or nifedipine (N) for two weeks, with D+F+S or N without C for two weeks, clinical status, chest X-ray picture and two dimensional echocardiography were evaluated at the end of each stage of the treatment. There were analyzed heart rate (HR), arterial systolic (Ps) and diastolic (Pd) blood pressure, body weight (Mc), 24-hour urinary output (Dd), cardio-thoracic index (CTI), cardiac volume index (CVI) and dimensions of the left ventricle: systolic (LVIDs), and diastolic (LVIDd). The mean daily doses of the drugs were as follows: D-0.290 +/- 0.108 mg, F-13.0 +/- 4.1 mg, S-44.5 +/- 9.8 mg, N-42.0 +/- 12.2 mg, and C-75.1 +/- 24.4 mg. The treatment with vasodilators (Vd) induced decreases in Mc, CVI, LVIIDs and LVIDd in comparison with the treatment with D and F. The largest lowerings in HR, Ps, Pd and Mc were observed during the treatment with D and F. The most beneficial effects with regard to CVI, LVIDs and LVIDd were obtained during four-week treatment with captopril. PMID- 1441520 TI - [Results of the treatment of Sjogren's syndrome with TFX (thymus factor X)]. AB - Seven patients with Sjogren's syndrome (6 with primary and 1 with secondary form of the syndrome developing during SLE) were treated with TFX Polfa in ampoules of 10 mg during 6-12 month. Before the treatment, besides evaluation of the general clinical condition, the following immunological parameters were determined: IgG, IgA and IgM levels, absolute lymphocyte count, T-cell and B-cell counts, absolute neutrophil count, antinuclear antibodies, circulating immune complexes and skin tests with recall antigens (tuberculin and distreptase). The clinical condition of the patients was determined at monthly intervals and the immunological investigations were repeated after the treatment which lasted 6-12 months. In all patients alleviation was observed of the clinical manifestations of the disease with decreased proneness to infections. In some patients improvement was observed of the determined immunological parameters, in the first place, reversal of cutaneous tests from negative to positive. PMID- 1441521 TI - [Value of laparoscopy in the diagnosis of liver cirrhosis and chronic hepatitis]. AB - The purpose of the study was evaluation of laparoscopy in the diagnosis of cirrhosis and chronic hepatitis. The studied material comprised 197 cases of cholestasis in which for diagnostic-prognostic purposes laparoscopy was done. During visual observation of the abdominal cavity in 81 cases cirrhosis and in 25 chronic hepatitis was diagnosed. The reliability of the laparoscopic diagnosis was verified by the microscopic verification of the material obtained by guided biopsy of the liver or during operation. Among 81 cases of cirrhosis diagnosed during laparoscopy histological confirmation was obtained in 68 cases (83.9%). In the group of 25 cases with laparoscopic diagnosis of chronic hepatitis the diagnosis was confirmed histologically in 21 (84%) cases. The authors believe that laparoscopy extends the diagnostic possibilities in liver diseases. However reliable diagnosis can be obtained by microscopic examination of liver fragments obtained by guided biopsy or operation. PMID- 1441522 TI - [Diagnostic and prognostic value of the assessment of selected indicators of humoral immunity in alcoholism-related pathology of the liver]. AB - The purpose of the study was evaluation of the usefulness of selected indices of humoral immune responsiveness in the differential diagnosis of post-alcoholic hepatocellular damage. The study was carried out in 105 patients: 10 patients with a history of alcohol abuse without clinical and biochemical evidence of hepatocellular damage, 2) patients with alcoholic cirrhosis, 3) patients with post-inflammatory cirrhosis. The prognostic usefulness of the determinations of serum IgM, C3 and C4 complement components and circulating immune complexes in early diagnostic of alcoholic liver disease was demonstrated. It was noted also that increased serum IgA level may be a useful index differentiating of cirrhosis after hepatitis from alcoholic cirrhosis. PMID- 1441523 TI - [Hepatitis A in drug addicts]. AB - In the years 1982-1988 among patients admitted with the diagnosis of acute virus hepatitis to the Department of Infectious Hepatology, Institute of Infectious and Parasitic Diseases in Warsaw were 25 drug addicts. In 15 of them virus hepatitis B and in 10 virus hepatitis A was recognized. Virus hepatitis A had in the group of addicts a milder course than in controls not taking narcotics. PMID- 1441524 TI - [Phenomenon of increased resistance of yeast-like fungi to nystatin]. AB - The results are presented of in vitro investigations of the sensitivity of 225 strains of yeast-like fungi to nystatin. The strains were isolated from cutaneous and mucosal lesions. In the study nystatin concentration 10 micrograms/ml of the substrate was used and a two-grade scale of evaluation was applied: sensitive or resistant to the drug. It was found that 56.7% of the tested strains were resistant to this nystatin concentration. The obtained data were compared with those obtained in 1972 when all the tested strains were sensitive to nystatin in this concentration. The study showed that the resistance to nystatin has been rising in these organisms with years. PMID- 1441525 TI - [Sliding hiatal hernia in endoscopic examination]. AB - Among 1000 successive endoscopic examinations carried out in the first 6 months of 1990 in a laboratory of endoscopy 443 cases (44.3%) of sliding hiatus hernia were analysed. The examination was carried out with an Olympus GIF-Q10 fibroscope without pharmacological premedication. The diagnosis was based on the criteria described by Dagradi and Trujillo at all. In 296 cases sliding hiatus hernia was the only pathological abnormality in the endoscopic examination. In 85 cases it was associated with mucosa inflammation in the oesophagus, and in 1 case with carcinoma of the oesophagus. No correlation was found between frequency of endoscopic finding of hiatus hernia and sex and age. The analysis showed that in 110 out of 172 cases earlier routine radiological examination (63.9%) failed to demonstrate the hernia, whose direct signs were found in endoscopic examination. In no case radiological findings suggested the presence of oesophageal changes. It seems that endoscopic diagnostic of sliding hiatus hernia may contribute to explanation of the cause of "non-characteristic" gastric symptoms which in over half the cases were the cause of referral of the patients to this examination. PMID- 1441526 TI - [Further studies of the acid plate agglutination reaction in the diagnosis of brucellosis in humans]. AB - Using the methods of acid platelet agglutination, agglutination, agglutination with 2-mercaptoethanol, Coombs' reaction, and complement binding reaction, 152 serum specimens taken from patients with diagnosed brucellosis, were subjected to studies. The following per cent of seropositive results was shown: acid platelet agglutination--11.2%, agglutination--40.1%, agglutination with 2-mercaptoethanol- 34.4%, Coombs' reaction--42.8%, complement binding reaction--7.9%. The acid platelet agglutination reaction cannot be used for screening for brucellosis in humans. PMID- 1441527 TI - [Silent myocardial ischemia]. PMID- 1441528 TI - [Fungal stomach ulcer]. AB - Fungal gastric ulcer is a relatively frequent from of gastric mycosis coexisting in 20-30% of cases with peptic ulcer. In such cases fungi were present in patients without other disease and in those with concomitant diseases such as neoplasms, polyps of the stomach, haematological diseases, and in patients treated with cytostatics and H2-blockers. Fungal ulcer differ from common ulcers in greater size and tendency for bleeding. In certain situations "fungal ulcer" requires routine antimycotic treatment especially if operation is planned. PMID- 1441529 TI - [Antiphospholipid syndrome]. PMID- 1441530 TI - [Acrodermatitis enteropathica--congenital zinc deficiency syndrome]. AB - The importance of the presence of zinc in human physiology and pathology has been analysed. The disturbances in the prostaglandin synthesis in the impaired intestinal zinc absorbtion have been of special interest. It is known that the deficiency of zinc results in the inborn clinical syndrome oh he disease and both its past and present treatment methods. PMID- 1441531 TI - [Severe exacerbation of chronic hepatitis B following interferon therapy]. AB - A patient with chronic active hepatitis B was treated with interferon alpha. Inhibition of HBV replication was associated with severe exacerbation of hepatitis. Treatment of chronic hepatitis B with interferon may lead to transient decompensation of liver function, especially in patients with high activity of morphological changes. PMID- 1441532 TI - [Burgdorf's reaction (painful acral erythema) in patients with acute lymphoblastic leukemia following medium-dose methotrexate therapy]. AB - Erythematous changes of the palms with associated oedema, blistering and desquamation were observed in two children during chemotherapy for acute lymphoblastic leukaemia, after methotrexate in doses of 1,000 mg/m2. These changes correspondent to those described in the literature as Burgdorf's reaction. In Poland it was never reported as yet. PMID- 1441533 TI - [A case of skin reactions to carbamazepine]. AB - A case is described of severe cutaneous complications after carbamazepine administration. Attention is called to the frequency of adverse reactions to this drug. PMID- 1441534 TI - [A case of side effect of Biseptol]. AB - A case of adverse side effects of co-trimoxazole (Biseptol) was observed, with predominance of neurological changes in the clinical picture. Attention is called to the infrequent occurrence of such side effects of this drug and to the necessity of prompt diagnostic and therapeutic management of such cases. PMID- 1441535 TI - [A case of non-Hodgkin's lymphoma of the thyroid gland]. AB - A case is reported of centrocytic-centroblastic malignant lymphoma situated in the thyroid and simulating goitre. Attention is called to difficulties in establishing of correct diagnosis. PMID- 1441536 TI - [Stress fracture of the clavicle]. PMID- 1441537 TI - [Epidemiological analysis of the correlations between selected individual characteristics of patients with primary arterial hypertension]. AB - The purpose of the study was to find the correlations and to evaluate their strength between the progression of hypertension and age, sex, time between the diagnosis of hypertension and the beginning of treatment, body weight and other characteristics. The study was carried out in the population of patients treated in the Cardiology Department, Medical Academy in Lublin in the period 1981-1984. The computer-assisted analysis of the obtained material was carried out in the Department of Epidemiology, Medical Academy in Lublin. The studied population comprised 320 patients with essential hypertension. In the statistical analysis the chi square test was applied for finding of statistically significant correlations and Pearson test was used for estimation of correlation strength. Statistically significant correlations were obtained between the progression of hypertension and age, sex, time between hypertension diagnosis and present treatment and body weight. PMID- 1441538 TI - [Occurrence of retrograde conduction after ventricular stimulation with the VVI pacemaker]. PMID- 1441539 TI - [Postoperative complications and mortality; results of skin tests in delayed hypersensitivity]. AB - In 221 patients the test of cutaneous delayed hypersensitivity was done before the operation and 4 days after it, using 3 antigens: tuberculin, distreptase and phytohaemagglutinin. The patients were divided into three groups: I control (109) subjected to minor and moderately serious operations, and study group (II) with peritonitis (IIa 40 cases), digestive tract cancer (IIb 65 cases) and digestive tract diseases (IIc 7 cases). The study showed that in cases with preoperative anergy to antigens the operations were followed significantly more frequently by serious septic complications and mortality from these complications was much higher. No patients with preoperatively normal responses to the antigens died after the operations. The test makes possible preoperative detection of high surgical risk connected with infection, and early treatment reducing postoperative mortality. PMID- 1441540 TI - [Elaboration of a device for detection of the ovulation period in women]. AB - The results are described of studies for evolving of modern methods for determination of the ovulation time in women. After an analysis of literature reports three methods were chosen based on differences in body temperature measurements and a measuring device for these experiments was designed. The results are presented of preliminary experiments with this method of "measurements of changes in the reactivity of blood vessels". Further studies can be conducted only by physicians, and the paper contains proposals of using this device as well as the literature data. PMID- 1441541 TI - [Results of the treatment of steroid-resistant and steroid-dependent nephrotic syndrome with pulsed doses of prednisolone]. AB - In 12 children with steroid-resistant and 17 with steroid-sensitive nephrotic syndrome massive doses of prednisolone were used in intravenous infusions ("pulses"). In 8 children with steroid-resistant and 9 with steroid-sensitive nephrotic syndrome very good or good results were obtained. The authors suppose that in a part of the children previous ineffectiveness of this immunosuppressive treatment could have been due to insufficient dosage. Rosette tests before and after pulses demonstrated a reduction of the total number of T-cells after pulses. The change of the ratio of theophylline-resistant to theophylline sensitive lymphocytes suggests that this reduction was caused mainly by a fall of the number of helper T-cells and non-specific cytotoxic cells. PMID- 1441542 TI - [Lung cancer among the autochthonous population and among immigrants Upper Silesia in relation to smoking, exposure to harmful factors at work and atmospheric pollution]. AB - By the case-control method 367 patients with lung carcinoma coming from the autochthonous population of Upper Silesia and 253 similar patients from the population of immigrants from other areas were compared (620 cases, in all) treated in the Institute of Oncology in Gliwice in the years 1982-1989. They accounted for about 85% of all male patients with this tumour. In the analysis three zones of Upper Silesia with varying concentrations of atmospheric pollution, where the patients lived, were considered, estimating the risk of this tumour in relation to pollution level, and standardizing the risk for tobacco smoking and considering data related to the exposure to harmful factors in occupational work. The analysis showed that the so called summarized index of relative risk was about 2.5 times greater for the autochthonous as well as immigrant populations in the zone of greatest atmospheric pollution with statistically significant differences in relation to the relatively most favourable zone (accepted as 1.00) However, the risk was progressively rising only in the autochthonous population (in all 3 zones). That showed that the risk of lung carcinoma was increasing in this population with increasing atmospheric pollution. This evident progression of risk was not found in the population of immigrants, although the risk level in this population living in the zone of greatest pollution was similar to that in the autochthonous population. PMID- 1441543 TI - [Surgical treatment of otosclerosis]. AB - The purpose of the study was evaluation of the surgical treatment of otosclerosis by the method of small and large window. On the basis of four conversation frequencies hearing improvement was assessed in 44 ears after operation. Closure of cochlear reserve to 10 dB was obtained in 70.5% of cases. The mean hearing improvement was 29 dB. The best results were obtained with stapedotomy (small window method), particularly at 4 kHz frequencies. PMID- 1441544 TI - [Endoscopic picture of hemorrhage from the upper digestive tract in elderly patients]. AB - The causes of upper gastrointestinal tract bleeding were analysed in 412 patients dividing them into age groups below and over 60 years. Both groups were compared using endoscopic classification of bleedings by Forrest. In the group aged over 60 years a significantly higher per cent of type II lesion was found, especially non-bleeding vascular stump protruding from the bottom of the ulcer. This lesion was associated in nearly half the cases with recurrence of bleeding. The finding of this endoscopic picture should suggest the necessity of a more radical operation, although the operative risk is higher in patients aged over 60 years. PMID- 1441545 TI - [Radioisotope methods of evaluation of myocardial blood flow]. PMID- 1441546 TI - [Primary sclerosing cholangitis and primary biliary liver cirrhosis as the causes of intrahepatic cholestasis]. AB - Primary sclerosing cholangitis and primary biliary cirrhosis are rarely diagnosed diseases which should, however, be considered in the diagnosis of cholestasis. The authors present an outline of the modern knowledge on these diseases with particular reference to differential diagnosis. PMID- 1441547 TI - [Non-ulcer dyspepsia]. AB - The definition, classification, pathophysiology, diagnosis and treatment of functional disturbances of the upper part of the digestive tract called "non ulcer dyspepsia" are described. Attention is called to the frequency of these disorders, and stress is laid on the role of digestive tract motor function tests in the knowledge of the pathophysiology and effective treatment. In the therapeutic proposals the authors prefer the use of prokinetic drugs, especially metoclopramide, domperidone and cisapridine. PMID- 1441548 TI - [Decidual prolactin]. AB - Human prolactin (hPRL) is a hormone produced by the lactotropic cells of the hypophysis and by the endometrium converted to decidua in pregnancy. Prolactin of decidual origin is identical with the pituitary hormone. Decidual prolactin is released mainly by the extraplacental fetal membranes. Prolactin production was found also in the endometrium in late secretory phase of normal menstrual cycle. It was noted that hPRL production by the decidua in various periods of pregnancy is closely correlated with hPRL concentration in the amniotic fluid. Peak hPRL release into the amniotic fluid is in the 24th week of pregnancy. The most important biological function of decidual prolactin is its effect on water and electrolyte transport for the needs of the fetus, and this transport takes place mainly across the fetal membranes. Moreover, it was found that prolactin affects the synthesis of fetal surfactant, influences calcium absorption in the fetal intestine. Calcium and phosphorus are obtained by the fetus from the amniotic fluid. Many authors suggest that decidual prolactin has a role in the process of implantation and early development of the blastocyst. PMID- 1441549 TI - [Recurrent acute chylous peritonitis]. AB - A case of acute chylous diffuse peritonitis with recurrences was treated by peritoneal drainage. During the first hospital stay this drainage resulted in cure. After 17 months another recurrence treated in the same way led to death with increasing renal failure, diabetes, cardiorespiratory failure. PMID- 1441550 TI - [Severe EPH gestosis complicated by development of complete HELLP syndrome]. AB - This is the first in Poland report on fully developed HELLP syndrome complicating severe EPH gestosis. The diagnosis and treatment of the syndrome are discussed in the light of a literature survey. PMID- 1441551 TI - [Treatment of hyperlipidemia in the prevention of ischemic heart disease. A proposal for the unification of medical management. I and II]. PMID- 1441552 TI - [4 years' methadone substitution therapy in Austria]. AB - On September 25th 1987 methadone was legalized for therapeutic use in Austria. During the past four years altogether 1828 opiate addicts were admitted to methadone maintenance treatment. 439 females and 926 males were currently being treated in December 1991; their age ranged from 16-59 years, the daily oral d,l methadone dose levels varied between 10 mg and 250 mg per day. Only 406 doctors and 123 pharmacies participate in methadone maintenance treatment, which does not provide complete cover for the area in spite of increased finding. Moreover, the doctors' skills in this treatment have to be improved by requisite training. As Austrian experience shows, methadone treatment offers a first step towards social rehabilitation for drug addicts who have been living as criminals on the fringe of society. Socioeconomic data, as well as criminal behaviour changed dramatically for the better due to this treatment in Austria. Physicians have a clear responsibility to lead the effort on all fronts in the implementation of this treatment modality. Therapeutic drug monitoring should become routine in methadone treatment to ensure compliance and to achieve optimum results, especially in patients who complain of withdrawal symptoms and continue high-risk behaviour and to increase acceptance of substitution therapy. The Austrian treatment model for methadone maintenance treatment is a positive example for other countries who wish to introduce this treatment modality for drug addiction. PMID- 1441553 TI - The diagnostic impact of magnetic resonance imaging on the evaluation of suspected spinal cord disease. AB - The data from 262 patients studied consecutively for suspected spinal cord disease were analysed to determine the utility of magnetic resonance imaging (MRI) in this clinical setting. Damage to the spinal cord was detected in a total of 188 (72%) patients and was caused by myelocompression in two thirds and by intramedullary lesions in one third of the patients. Misleading sensory levels 5 to 12 segments below the actual lesion site were seen in 26% of patients with both extra- and intramedullary types of abnormality. A negative spinal MRI implied predominantly demyelinating or inflammatory origin of the clinical symptomatology, as was indicated by additional MRI studies of the brain and CSF findings. It is concluded that MRI is the procedure of choice for assessing patients with medullary symptoms. Irrespective of localizing neurologic findings the evaluation of the entire spine and even of the brain may be necessary to obtain maximum diagnostic information. PMID- 1441554 TI - [Epidemiology of suicide in Austria 1980 to 1990]. AB - This article investigates the suicide rates in Austria from 1980 to 1990 according to age groups and the methods used. In the years investigated the overall suicide rate increased until 1986, followed by a decline until 1990. The suicide rate in women shows a gradual linear increase with age, whilst in men there is a biphasic curve with a steep increase in teenagers and young men in their early twenties, followed by a plateau and a second steep increase as from 65 years of age, whereby the increase from "60-64 years" to the age group "over 85 years" is 134%. Regarding the age groups the decline over the past years in women is biggest in the groups "35-39 years" and "65-69 years", with men a decrease is present in the age groups from 20 to 50 years. Concerning the methods used, hanging is the most common mode of suicide in both women (36.4%) and men (48.8%). Suicide in the elderly--particularly in old men--which has increased internationally over the past few decades is targeted as the major area for vigorous preventive measures in Austria. PMID- 1441555 TI - [Randomized field study of the etiology of strabismus concomitans]. AB - After an introduction to the problems of binocular vision and an overview of the literature, the authors report on the reasons for undertaking this study and on its practical implications. Up to now, no other randomized study has been undertaken to our knowledge on children of this age group in such a large city as Vienna. All children in primary 3 classes in 20 out of the 256 elementary schools were examined ophthalmologically and orthoptically. It was found that hereditary factors are of statistically significant importance. Especially important for the ophthalmologist is also the statistically significant relation between the diagnosis poor range of fusion, poor fixation, incorrect Worth test for distance and/or proximity, and poor or lacking stereoscopic vision with the occurrence of strabism. The authors were astonished to find a remarkably high percentage of exophoria (58%), in contrast to esophoria (16%). It is interesting for prophylaxis and therapy that children originating from families where spectacles are worn, acted more cooperatively and tended to take the orders of the physician more seriously than those coming from families without eye problems. The promotion of genetic research related to squint and more counselling for couples wishing to have children or confronted with risk factor problems would be desirable, as well as the inclusion of more obligatory ophthalmological examinations in the mother-child medical "passport". PMID- 1441556 TI - Laminar heterotopic grey matter (double cortex) in a patient with late onset Lennox-Gastaut syndrome. AB - The Lennox-Gastaut syndrome (LGS) is a severe epileptic disorder, characterized by developmental delay, typical electroencephalographic pattern and poor control of seizures. This epileptic syndrome generally presents in early childhood but exceptionally starts at the age of 5 years or later. We describe a patient who was classified as late-onset LGS, with evidence of mild hydrocephalus on CT. MRI added new diagnostic information by demonstrating laminar heterotopic grey matter. PMID- 1441557 TI - [Role of the supplementary motor area for spatial parameters of bimanual movements]. PMID- 1441558 TI - [Neurologic symptoms within the scope of endocrine emergencies]. AB - Functional disturbances of the central and peripheral nervous system can be seen in various internal diseases and it is not unusual that neurological symptoms are the first kind of presentation. The tight anatomical and functional junction between neurology and endocrinology predisposes to the development of neurological derangements such as somnolence, coma, seizures, and focal signs following endocrinological emergencies. In spite of modern imaging and laboratory methods, history and clinical examination are still of great importance to establish the correct diagnosis. PMID- 1441559 TI - Hemodynamic findings in migraine patients on transcranial Doppler sonography. AB - Forty migraine patients were examined by means of 3D-transcranial Doppler scanning (TCD). The complete circle of Willis was investigated in all patients during headache-free intervals. TCD investigations were repeated in 10 patients during a migraine attack, in one patient twice. Based on the diagnostic criteria of the "headache classification committee of the international headache society" 23 patients were assigned to a "migraine without aura" group and 17 to a "migraine with aura" group. Twenty age-matched volunteers, not suffering from headache or any vascular disease, served as a control group. No significant differences were detected between the hemodynamic data of the control group and the migraine groups both with respect to the headache-free interval and the attack. No hemodynamic changes in keeping with the pathophysiologic hypothesis of vasospasm were found in the proximal segments of the basal cerebral arteries. PMID- 1441560 TI - [Smoking is a risk factor for spinal diseases. Hypothesis of the pathomechanism]. AB - Epidemiological studies strongly imply that smoking is a risk factor for back problems. The question arises as to the nature of the underlying pathomechanism. Several theories are currently discussed in the literature: it could be due to "unhealthy" life styles associated with smoking, to a rise in intraabdominal pressure caused by frequent coughing, or to osteoporosis of smokers. All of these hypotheses, however, do not stand up to a critical examination of the experimental evidence. A new theory is, therefore, put forward, claiming that smoking leads to malnutrition of the discs, which in turn renders them more vulnerable to mechanical stress. Malnutrition can be brought about by CO-Hb formation, vasoconstriction, arteriosclerotic vessel wall changes, impairment of fibrinolytic activity and changes in the flow properties of blood, all of which are known effects of smoking. The evidence for these pathomechanisms is discussed. Future studies should test the above hypothesis experimentally. PMID- 1441561 TI - [Perspective in the incidence of Alzheimer's disease in Austria by the year 2050]. AB - Population projections of the Austrian Central Statistical Office show a dramatic increase in the proportion of people of 65 years of age and over in Austria by the year 2050. Since this population group is at higher risk to develop Alzheimer's disease (AD/SDAT), it will be necessary to modify the currently available facilities for social and medical care to meet this increasing demand. Based on official demographic data and epidemiological findings of the "Eurodem" group, our computations show that the number of persons with AD/SDAT aged 65 or over will rise from 48,000 at present to over 113,500 in 2050 (1990: 614/100,000, 2050: 1505/100,000 persons of the total population), equivalent to an increase of 140%. By forecasting the number of persons affected, it should be possible to intensify (and in some areas introduce) long-term health planning with respect to the social, financial and medical care of aged, demented people in Austria. PMID- 1441562 TI - [Video-endoscopic interventions in thoracic surgery]. AB - Between October and December 1991 we performed videoendoscopic procedures, including resection of lung tissue, on 9 patients in our thoracic surgery unit. A lung measuring 15 x 18 was extirpated in 1 patient and parietal pleurectomy was performed after complicated pneumothorax in 4 patients. In one of these cases it was necessary to close a parenchymal leak and in 3 cases bullae had to be removed. Resection was undertaken in 4 patients for peripheral lung nodules, in one of them for metastases. Two patients proceeded to conventional lobectomy immediately after the frozen section results came through. Closure of lung parenchyma was carried out by means of the new ENDO-GIA stapler. Duration of the procedure was less than one hour except in the case of one patient. In one case it was necessary to use three cannulae. In the other cases two cannulae (one for videoendoscopy and fixating instrument, one for preparation instrument and stapler) sufficed for the operation to be undertaken without difficulty. This new technique brings all the known advantages of minimal invasive intervention to patients requiring thoracic surgery. PMID- 1441563 TI - [Laparoscopic cholecystectomy--evaluation of a prospective follow-up study]. AB - A report is presented on 105 patients who underwent laparoscopic cholecystectomy because of symptomatic gallstone disease. Preoperative and intraoperative findings, complications and results were prospectively documented. In four (3.8%) patients the laparoscopic procedure had to be converted into open cholecystectomy. There were only minor surgical complications such as wound infection and a subhepatic haematoma. On average, patients were discharged on the second postoperative day. The operating time decreased from a median of 98 minutes in the first half to 73 minutes in the second half of the study, despite augmentation of the number of surgeons and of the indications to include patients with acute cholecystitis (n = 11), previous upper abdominal surgery (n = 7) and cirrhosis (n = 2). PMID- 1441564 TI - [Spinal meningoceles. Diagnosis--microsurgery--long-term results]. PMID- 1441565 TI - [The Hypertension Optimal Treatment Study. Background information]. PMID- 1441566 TI - [Anabolic steroids in athletes]. AB - The use of anabolic-androgenic steroids (AS) to enhance appearance as well as physical/physiological capacities has increased dramatically over the past four decades in all age groups from early adolescence to adulthood. Although higher AS use rates are reported by elite and competitive athletes, a significant number of recreational athletes appear to be using AS. The scientific literature is inconsistent and at times at odds with the conventional wisdom and empirical experiences of the athletic community regarding the ergogenic effects of AS. However, individuals experienced in weight training, with an adequate diet, and who continue training during AS administration seem to consistently increase their strength and lean mass over what would have been expected from training alone. Previous research documenting deleterious but transient and mostly asymptomatic acute changes in physiology, risk factors and behavior has been inconclusive regarding the long term health impact. The abuse of AS constitutes a special challenge to society. AS are not euphorigenic or mood altering immediately following administration, as are other illicit drugs; the appetite for AS has been created predominantly by our societal fixations on winning and physical appearance. Consequently any successful intervention in this area must go beyond education, law enforcement and drug testing, and attempt to change a social environment which currently encourages the use of AS. PMID- 1441567 TI - [Aerobic upper body training. An underutilized potential in training therapy]. AB - Until recently, there was little or no emphasis on aerobic upper body exercise training, despite research strongly supports the inclusion of this type of exercise in cardiac rehabilitation programs and adult fitness. The limited degree of transfer of training benefits from trained limbs to another set of untrained limbs appears to discount the practice of recommending aerobic leg exercise alone. In addition, leg training programs fail to accommodate individuals with specific health problems. There is an increased physiological stress during arm training, if compared to leg training. Exercise intensity derived from a bicycle- or treadmill test would therefore cause an inappropriately target heart rate for upper body exercise. Thus, target heart rate has to be reduced by 10 to 20% to be adequate for aerobic arm training. Finally, an example of a progressive arm exercise training program is shown. PMID- 1441568 TI - [Females in performance sports from the sports medicine viewpoint]. AB - Especially in the endurance disciplines, the performance of women went up considerably in the course of the past few decades. This seems to be peculiar to the female sex and can be taken as a hint to a higher adaptability of the female organism with respect to the various motor capacities required for strength and endurance. During the past 10 years, however, the rate, with which the performance gap in the endurance disciplines narrowed, has slowed down distinctly. Thus, it seems, that the era during which the women vigorously caught up on the men, is coming to an end in the endurance sports. The different capacity of the sexes with respect to strength is rooted in the differently dimensioned cross sections of the muscle fibres and in the higher activation capability of the skeletal muscles of men. No differences exist with respect to the relative proportions of the ST-, FTa- and FTb-fibres and with respect to the biochemistry of the muscles. Just as in case of men, the adaptation of the cardiovascular system to endurance training manifests in a uniform enlargement of all of the heart's cavities. It is true, that women have a smaller heart volume and lower values for the maximum oxygen uptake, but these differences or by no means related to sex alone. Very often, they are produced by the fact that the endurance training of the women did not go that far. As regards the energy substrates, there is the hypothesis that women have better utilization of free fatty acids under conditions of prolonged and intensive physical work.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441569 TI - Lymphatic filariasis: the disease and its control. Fifth report of the WHO Expert Committee on Filariasis. PMID- 1441570 TI - WHO Expert Committee on Biological Standardization. PMID- 1441571 TI - Politics and war. PMID- 1441572 TI - Management of neck pain. PMID- 1441573 TI - Musculoskeletal pain and work disability. AB - Musculo-skeletal pain caused by neck and back injury, cumulative trauma to the upper extremities, fibromyalgia, and reflex dystrophy is an important cause of worker disability. Physicians are involved not only in the care of injured workers, but in providing independent medical opinions regarding such injuries. Advances in medical knowledge permit better understanding and management of these injuries, and it is the responsibility of all physicians to provide accurate diagnosis, treatment, and information to patients, employers, insurers, and the workers compensation system. PMID- 1441574 TI - Occupational low back pain: prevention of chronic disability. AB - Work-related low back pain is a major problem for both patients and employers. Although the cause of the pain is often unclear, patients failing to return to work within 3 to 6 months have a poor medical and economic prognoses. This article reviews issues relevant to the need for aggressive management of acute, work-related LBP cases. PMID- 1441575 TI - Occupational soft tissue disorders of the hand and forearm. AB - Upper extremity work-related diagnoses are becoming more frequent as a source of chronic pain and lost work time for the injured worker. Early directed care toward diagnosis, treatment, and rehabilitation is needed to prevent a protracted course. A review of common regional problems of the upper extremity is presented. PMID- 1441577 TI - Assessment of disability status: the role of the physician. PMID- 1441576 TI - Fibromuscular pain disorders in the injured worker: accurate examination is the key to diagnosis. PMID- 1441578 TI - Review process for reasonableness of fees and necessity of treatment disputes involving Worker's Compensation cases. PMID- 1441579 TI - Physicians and the Worker's Compensation system. PMID- 1441580 TI - Breast cancer survival in Wisconsin. PMID- 1441581 TI - The Gundersen legacy. PMID- 1441582 TI - Nutritional factors and the etiology of non-insulin-dependent diabetes mellitus: an epidemiological overview. PMID- 1441583 TI - The affluent diet and its consequences: Saudi Arabia--a case in point. PMID- 1441584 TI - Vitamins and hypertension. PMID- 1441585 TI - Long-chain omega 3 fatty acids are the most effective polyunsaturated fatty acids for dietary prevention and treatment of cardiovascular risk factors. Conclusions from clinical studies. PMID- 1441586 TI - Molecular cloning of a cDNA for rat diabetes-inducible cytochrome P450RLM6: hormonal regulation and similarity to the cytochrome P4502E1 gene. AB - 1. A polyclonal, monospecific antibody to a constitutive, diabetes-inducible and insulin-reversible cytochrome P-450 isozyme (RLM6) was used to screen a male rat liver cDNA library in lambda gt 11. Six clones harbouring the RLM6 cDNA insert were isolated initially from the expression library and three of these were further plaque-purified and sub-cloned. A 1.1 Kb cDNA insert, representing approximately 65% of the expected full length cDNA was characterized by restriction endonuclease mapping and sequenced by the dideoxy chain-termination method. Comparison of the nucleotide sequence of RLM6 cDNA to that of ethanol inducible P4502E1 rat cDNA showed the two cDNAs to be identical, the RLM6 cDNA corresponding to nucleotides 310-1402 of the P4502E1 sequence. 2. RLM6 cDNA probe was used in Northern blot and RNA dot blot hybridization analysis to demonstrate that both streptozotocin-induced diabetes and fasting significantly elevated the steady-state level of RLM6 mRNA in male rat liver. Increased RLM6 mRNA level in the diabetic rat resulted in increased RLM6 apoprotein synthesis when polysomal RNA was used in a cell-free, protein-synthesizing system, indicating that the elevated RLM6 level observed in diabetic rats was correlated directly with the increased RLM6 mRNA concentration. 3. Daily insulin treatment of diabetic rats reversed the diabetes-dependent increase in RLM6 mRNA in a time-dependent manner, returning to control values after approximately 2 weeks of continuous insulin treatment. This insulin-dependent decrease of the RLM6 mRNA level was paralleled by a similar time-dependent decrease in serum acetone concentration. 4. Treatment of the male diabetic rat with testosterone also resulted in a decrease in both RLM6 mRNA and in vitro translated apoprotein. 5. Modulation of RLM6 mRNA level in the diabetic rat by insulin and testosterone, and the nucleotide sequence similarity with that of P4502E1 confirms that diabetes-inducible P450RLM6 and ethanol-inducible P4502E1 are coded for by the same gene. PMID- 1441587 TI - Bacterial metabolism of 2,6-dinitrotoluene with Salmonella typhimurium and mutagenicity of the metabolites of 2,6-dinitrotoluene and related compounds. AB - 1. Metabolites produced by the incubation of 2,6-dinitrotoluene (2,6-DNT) with Salmonella typhimurium strains TA 98, TA 98/1,8-DNP6 and TA 98NR were examined. Mutagenicities of bacterial products and related compounds were also examined in the Ames assay using TA 98 and TA 100. 2. 2,6-DNT was converted to 2-nitroso-6 nitrotoluene, 2-hydroxylamino-6-nitrotoluene and 2-amino-6-nitrotoluene, with concurrent spontaneous formation of 2,2'-dimethyl-3,3'-dinitroazoxybenzene, in the incubation with TA 98 and TA 98/1,8-DNP6. Capacity of TA 98NR to reduce 2,6 DNT was much lower than that of TA 98 and TA 98/1,8-DNP6. 3. Bacterial products, including 2,2'-dimethyl-3,3'-dinitroazoxybenzene, showed no mutagenic activity in the Ames assay. 4. Results indicate that the lack of mutagenic activity of 2,6 DNT is not due to low reductive metabolism of 2,6-DNT by bacteria, but due to the lack of mutagenic activity of the bacterial reductive products of 2,6-DNT. PMID- 1441588 TI - Bioanalytical applications of tandem mass spectrometry in the in vitro metabolism of the anticholinergic drug cimetropium bromide to detect differences in species metabolism. AB - 1. In vitro metabolism of the anticholinergic drug, cimetropium bromide, was investigated using four different animal hepatic microsomal incubates derived from rat, hamster, guinea pig, and mouse livers. 2. Constant neutral loss (CNL) tandem mass spectrometry was used to detect the presence of the N methylenecyclopropyl-scopine functionality by monitoring loss of 54 daltons (corresponding to loss of methylenecyclopropane) in microsomal incubates. 3. A CNL loss of 46 daltons was used to screen for the presence of ester hydrolysis products. 4. A comparison of the daughter ion spectra obtained on ions detected by CNL scanning, with daughter ion spectra of synthetic standards, determined the presence of ten metabolites of cimetropium bromide. 5. Hydroxylation of the aromatic ring in the ester side-chain was found to be the major metabolic pathway, and ester bond hydrolysis was a minor metabolic pathway. 6. N Demethylation of the bridgehead nitrogen was observed only in rat and hamster incubates. 7. Using the method of CNL scanning it was possible to screen different animal microsomal incubates without resorting to any major purification procedures such as h.p.l.c. 8. This scanning method revealed differences between species in the metabolic pathways of cimetropium bromide. PMID- 1441589 TI - Differences in the metabolism of the antitumour agents amsacrine and its derivative CI-921 in rat and mouse. AB - 1. Rats and mice were treated with the antitumour agent CI-921 (I), and parent compound amsacrine, with all biliary metabolites being analysed. 2. In both rat and mouse the major biliary metabolites of amsacrine are the 5'- and 6' glutathione (GSH) conjugates, with no C9-GSH conjugate being detected. 3. 5'- and 6'-GSH conjugates of I are also formed in both species. However, two additional products were detected and their structures confirmed by liquid secondary ion mass spectrometry and 1H-n.m.r. spectrometry, and by comparison with synthetic standards. 4. Additional metabolites of I are the C9-GSH conjugate and the 4 hydroxymethyl derivative which, either as the aglycone or glucuronide, is the predominant product in rat bile (comprising 56% of the dose eliminated over 3.5 h). 5. Relative amounts of the C9-GSH conjugate to the 5'- and 6'-GSH conjugates to the 4-hydroxymethyl derivatives, were 24:65:10 in mouse bile and 2:8:90 in rat bile. 6. These differences indicate first, likely enzyme involvement in the formation of the C9-GSH conjugate of I, and second, in comparison with amsacrine, alternative pathways which may decrease formation of the reactive quinone diimine intermediate of I and consequent hepatotoxicity. PMID- 1441590 TI - Interspecies variations in caffeine metabolism related to cytochrome P4501A enzymes. AB - 1. Interspecies (including man, monkey, rabbit, rat and mouse) variations in caffeine metabolism by liver microsomes were studied. While N-3 demethylation was the major pathway in man (81% of total dimethylxanthines), N-7 demethylation was predominant in monkey (89%), and the three demethylation pathways were about equal in mouse, rabbit and rat. 2. Three monooxygenase activities (methoxyresorufin O-demethylase, phenacetin O-deethylase and acetanilide 4 hydroxylase) correlated significantly with the rate of metabolism of caffeine. 3. P4501A1 and 1A2 enzymes were immunodetected in different species. P4501A2 was the only isoform detected in liver of man, rat and mouse, while no polypeptide immunorelated to P4501A was detected in monkey and only a minor band of P4501A1 was detected in rat and rabbit. 4. All in vitro data indicate that paraxanthine formation is mediated mainly by P4501A2 in mammals while theophylline formation is mediated mainly by cytochromes P-450 other than those of the 1A family. PMID- 1441591 TI - Disposition and biotransformation of pentachlorophenol in the red abalone (Haliotis rufescens). AB - 1. The disposition and biotransformation of pentachlorophenol (PCP) in the red abalone (Haliotis rufescens) have been determined. 2. In a flow-through system, three abalones were exposed to 1.2 mg/l of [U-14C]PCP for 5 h to determine bioconcentration and tissue distribution. Retained residues were quantified from radioactivity, while excreted residues were identified and quantified by h.p.l.c. and determination of radioactivity. 3. The 5-h total concentration factor ranged from 16.0 to 21.5; individual tissue concentrations ranged from 133.4 nmol/g in gill to 17.5 nmol/g in gonad. Due to its large size, the foot muscle received the largest amount of total retained residue (47.4%). 4. During a 13-h recovery period the abalones depurated 72.2% of retained residues; however, residue concentration in gonad increased over 100%. PCP was primarily excreted unchanged (89.3%), but small amounts of pentachloro-beta-D-glucoside (7.9%), pentachloroanisole (1.3%), pentachlorophenylsulphate (0.9%), and tetrachloro-p hydroquinone (0.6%) were also formed. PMID- 1441592 TI - Purification and molecular properties of 2-carboxybenzaldehyde (CBA) reductase from phenobarbital-treated rat liver. AB - 1. A rat liver cytosol enzyme, tentatively named CBA reductase, catalyses the conversion of 2-carboxybenzaldehyde (CBA) to 2-hydroxymethyl benzoic acid in the presence of NADH (or NADPH). CBA reductase is useful for exploring the mechanism of in vitro enzyme induction, as the enzyme can be induced by phenobarbital (PB) both in vivo and in vitro. 2. Possible involvement of glutathione (GSH) in gene expression was suggested by a recent study with cultured rat hepatocytes. 3. CBA reductase was purified about 200-fold by a combination of column chromatography and isoelectric focusing in the presence of mercaptoethanol. 4. The ability to form 2-hydroxymethyl benzoic acid was lost when the enzyme was chromatographed on a hydroxylapatite column in the absence of mercaptoethanol; however, it was restored if sulphydryl compounds or bovine serum albumin was added to the eluate from the column. 5. Gel filtration showed the molecular sizes of CBA reductase from the 105,000g supernatant fraction of rat liver extracts and the purified preparation were 64 kDa and 49 kDa, respectively. 6. The results suggest that sulphydryl substances and some proteins play important roles in preserving the molecular and catalytic properties of CBA reductase. PMID- 1441593 TI - Intestinal metabolism of mephentermine and its biliary metabolites in male Wistar rats. AB - 1. Intestinal metabolites produced in the incubation (0-24 h) of mephentermine (MP), phentermine (Ph), N-hydroxymephentermine (N-hydroxy-MP), N hydroxyphentermine (N-hydroxy-Ph), p-hydroxymephentermine (p-hydroxy-MP) and p hydroxyphentermine (p-hydroxy-Ph) with male Wistar rat intestinal contents under N2 were examined by g.l.c. and g.l.c.-electron impact (EI) mass spectrometry. Metabolites produced in the anaerobic incubation of bile from rats given MP, with the intestinal contents were also examined. In addition, urinary and biliary metabolites of p-hydroxy-MP and p-hydroxy-Ph dosed orally to rat were examined. 2. Metabolites in the anaerobic incubation of N-hydroxy-MP and N-hydroxy-Ph were MP and Ph, and Ph, respectively. No metabolites were detected in the incubation of MP, Ph, p-hydroxy-MP and p-hydroxy-Ph. 3. p-Hydroxy-MP and p-hydroxy-Ph (major), and MP and Ph (minor) were detected when bile from rats given MP was incubated with intestinal contents. 4. Unchanged p-hydroxy-MP, and conjugates of p-hydroxy-MP and p-hydroxy-Ph, were detected in the 24-h urine of rats dosed with p-hydroxy-MP, which accounted for about 3, 72 and 1% dose, respectively. Unchanged p-hydroxy-Ph and conjugated p-hydroxy-Ph were detected in the 24-h urine of rats dosed with p-hydroxy-Ph, which accounted for about 4 and 68% dose, respectively. 5. Conjugated p-hydroxy-MP and conjugated p-hydroxy-Ph, which accounted for about 3% doses, were detected in the 24-h bile of rats dosed with p hydroxy-MP and p-hydroxy-Ph.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441594 TI - Pharmacokinetics and metabolism of dofetilide in mouse, rat, dog and man. AB - 1. Pharmacokinetics of dofetilide were studied in man, dog, rat and mouse after single i.v. and oral doses of dofetilide or 14C-dofetilide. 2. Dofetilide was absorbed completely in all species. Low metabolic clearance in man resulted in complete bioavailability following oral administration. Higher metabolic clearance in rodents, and to a lesser extent dogs, resulted in decreased bioavailability because of first-pass metabolism. 3. Following i.v. administration, the volume of distribution showed only moderate variation in all species (2.8-6.3 l/kg). High plasma clearance in rodents resulted in short half life values (mouse 0.32, male rat 0.5 and female rat 1.2 h), whilst lower clearance in dog and man gave longer terminal elimination half-lives (4.6 and 7.6 h respectively). 4. After single i.v. doses of 14C-dofetilide, unchanged drug was the major component excreted in urine of all species with several metabolites also present. 5. Metabolites identified in urine from all species were formed by N-oxidation or N-dealkylation of the tertiary nitrogen atom of dofetilide. 6. After oral and i.v. administration of 14C-dofetilide to man, parent compound was the only detectable component present in plasma and represented 75% of plasma radioactivity. No single metabolite accounted for greater than 5% of plasma radioactivity. PMID- 1441595 TI - Stereoselective inhibition of nortriptyline hydroxylation in man by quinidine. AB - 1. Four volunteers phenotyped as extensive metabolizers of sparteine took 25 mg nortriptyline hydrochloride and collected urine for 72-80 h. Total free and conjugated 10-hydroxynortriptyline (10-OH-NT) accounted for 54-58% of the dose and it was reduced to 25-40% when 50 mg quinidine sulphate was ingested on the first and second day. 2. Of the four isomers of 10-OH-NT, (-)-E-10-OH-NT was selectively decreased in quantity by quinidine coadministration, while the (+) isomer and (-)- and (+)-Z-10-OH-NT were found in unchanged or slightly increased quantities. The contribution of (-)-E-10-OH-NT to total E-10-OH-NT and the E-/Z ratio in total 10-OH-NT were significantly reduced. 3. The quantity of the phenol, 2-hydroxynortriptyline in urine was decreased by quinidine; the relative amounts of metabolites with a primary amino group were not affected. 4. Liver microsomes from a donor in which cytochrome P450IID6 was shown to be present by in vitro phenotyping metabolized NT to E-10-OH-NT containing 86% of the (-) isomer. Quinidine reduced the hydroxylation rate in (-)-E-10-position much more than that in (+)-E-10-position. 5. Since quinidine selectively impairs the function of cytochrome P450IID6, it is concluded that this isoform catalyses NT hydroxylation predominantly in (-)-E-10- and in 2-position. PMID- 1441596 TI - Transgenic animals in the evaluation of compound efficacy and toxicity: will they be as useful as they are novel? AB - 1. Construction of transgenic mice is predicated upon inserting foreign DNA into native host DNA and having this expressed in the germline. This may be accomplished by nuclear injection, retroviral vectors or use of embryonic stem (ES) cells. 2. Expression of novel structural genes may be reasonably directed by the judicious use of an accompanying promoter/enhancer sequence. Insertion of foreign genes may be designed to result in phenotypic expression of a novel trait or ablation of a native gene or gene product. 3. Resulting transgenic mice offer significant utility as models of human diseases and a unique opportunity for investigating immune and metabolic pathways as well as for exploring mechanisms of development, mutagenesis and teratogenesis. 4. Use of transgenic animals in drug development has considerable potential although realization of this potential will take time. Constructing transgenics is only the first step in a complex series of events culminating in understanding the consequences of imposing novel genetic material on an intact, highly integrated living system. Practical use of transgenic animals will depend upon substantial effort being spent in investigating and validating the phenotypic consequences of gene transfer. PMID- 1441597 TI - Methylation pharmacogenetics: thiopurine methyltransferase as a model system. AB - 1. Methyl conjugation is an important pathway in the biotransformation of many drugs and xenobiotic compounds. 'Pharmacogenetic' variation exists in the activities of many methyltransferase enzymes, and experiments with the drug metabolizing enzyme thiopurine methyltransferase (TPMT) offer a model for one approach that has proven useful in the study of methyltransferase pharmacogenetics. 2. TPMT catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. This enzyme activity is present in the human red blood cell (RBC), and RBC TPMT activity is controlled by a common genetic polymorphism that regulates also the enzyme activity in all other human tissues that have been studied. 3. Subjects with inherited low levels of TPMT activity are at increased risk for thiopurine drug-induced myelotoxicity, while patients with high TPMT activities may be 'undertreated' with these drugs. 4. TPMT activity in tissue from selected strains of inbred mice also is regulated by a genetic polymorphism. These mice provide an animal model for use in the study of pharmacological or toxicological consequences of inherited differences in TPMT activity. 4. Other methyltransferase enzymes including thiol methyltransferase, catechol O methyltransferase, and histamine N-methyltransferase also are present in the human RBC, are regulated by inheritance, and are responsible for individual variation in drug metabolism. Enhanced understanding of the pharmacogenetics of methylation may make it possible to understand and predict individual variation in the biotransformation, toxicity and therapeutic effect of compounds that undergo methyl conjugation. PMID- 1441598 TI - Polymorphisms of N-acetyltransferase genes. AB - 1. A genetic polymorphism of human liver arylamine N-acetyltransferase (NAT) enzyme activity leads to wide variation in the disposition of many drugs and potential carcinogens, resulting in differential susceptibility to chemical induced toxicity. 2. During studies to determine the biochemical and molecular mechanisms underlying this pharmacogenetic defect, we cloned two human genes, NAT1 and NAT2, which encode the functional acetylating enzymes NAT1 and NAT2. 3. NAT1 and NAT2 are both expressed in human liver cytosol, the latter as two closely related isoforms NAT2A and NAT2B. 4. NAT2 gene locus is the site of the human acetylation polymorphism, because its products NAT2A and NAT2B selectively acetylate 'polymorphic' arylamine substrates (e.g. sulphamethazine), and since the liver content of these isozymes is markedly reduced in genetically slow acetylator subjects. 5. NAT1 shows marked kinetic selectivity for 'monomorphic' substrates (e.g. p-aminobenzoic acid) whose in vivo acetylation rates do not correlate with the acetylation polymorphism. 6. Despite the drastic reduction in NAT2A/B proteins in livers from phenotypically slow acetylators, levels of the NAT2 gene transcript are not altered. 7. Three common mutant alleles at the NAT2 gene locus have so far been identified, which may be detected by restriction fragment length polymorphism (RFLP) analysis on Southern blots or by allele specific polymerase chain reaction amplification. PMID- 1441599 TI - Polymorphism in stereoselective hydroxylations of mephenytoin and hexobarbital by Japanese liver samples in relation to cytochrome P-450 human-2 (IIC9). AB - 1. Stereoselective 4'-hydroxylations of R-(--)-mephenytoin and S-(+)-mephenytoin were determined in liver microsomes of 19 Japanese subjects. 2. The content of P 450 human-2 assessed by Western-blots correlated with microsomal S-(+) mephenytoin 4'-hydroxylation. Antibody raised against P-450 human-2 effectively inhibited microsomal S-(+)-mephenytoin 4'-hydroxylation, but was less efficient for inhibition of R-(--)-mephenytoin 4'-hydroxylation in extensive metabolizers, and 4'-hydroxylation of both mephenytoin enantiomers in poor metabolizers. 3. Similar results were observed on the stereoselective hydroxylations of R-(--)- and S-(+)-hexobarbital. Clear correlations were observed for the content of P-450 human-2 and microsomal R-(--)-hexobarbital 3'alpha-hydroxylation and S-(+) hexobarbital 3'beta-hydroxylation. 4. Moreover, yeast microsomes expressing P-450 human-2 cDNA showed high stereoselectivities for hydroxylations of mephenytoin and hexobarbital similar to those observed in human liver. 5. Two other cytochromes P-450(IIC 9/10) expressed in yeast, whose cDNA were synthesized by site-directed mutagenesis from human-2 cDNA, showed no stereoselectivity for the hydroxylations of mephenytoin and hexobarbital, in spite of the modification of only two amino acid substitutions or deletions in the whole sequence. 6. Only a cytochrome derived from P-450 human cDNA corresponding to P-450 human-2 was expressed in human livers, the two cytochromes of the three related IIC9/10 forms were not expressed. 7. These findings indicate that P-450 human-2 is the major cytochrome P-450 responsible for the polymorphisms in stereoselective hydroxylations of mephenytoin and hexobarbital. PMID- 1441601 TI - Co-induction of cytochrome P4504A1 and peroxisome proliferation: a causal or casual relationship? AB - 1. The hypothesis that xenobiotic induction of hepatic microsomal cytochrome P4504A1 and peroxisome proliferation are closely-related phenomena has been further investigated. 2. Five rat strains (Gunn, Fischer, Wistar, Long Evans and Sprague Dawley) were all susceptible to xenobiotic induction of both microsomal cytochrome P4504A1 and peroxisome proliferation, and no strain exhibited a dissociation of these phenomena. 3. In comparison to rat, the marmoset was substantially less susceptible to the above hepatic changes. 4. Induction of both cytochrome P4504A1 and peroxisome proliferation by a structural analogue of clofibrate (2-(4-(4-chlorophenyl)benzyloxy)-2-phenyl acetic acid) demonstrated stereochemical selectivity, in that the R(-)-isomer was a more potent inducer of both phenomena than the S(+)-antipode, with the racemic mixture exhibiting an intermediate potency. 5. Cycloheximide inhibition of clofibrate-dependent induction of acyl CoA mRNA, but not cytochrome P4504A1 mRNA has indicated a protein dependency for peroxisome proliferation, not inconsistent with participation of cytochrome P4504A1 in the biogenesis of peroxisome proliferation. 6. Taken collectively, the data described herein provide further evidence for a close linkage between xenobiotic induction of cytochrome P4504A1 and peroxisome proliferation, and possible molecular mechanisms inter-relating these two phenomena are discussed. PMID- 1441600 TI - Applications of stable V79-derived cell lines expressing rat cytochromes P4501A1, 1A2, and 2B1. AB - 1. Chinese hamster V79-derived cell lines, stably expressing cytochromes P4501A1, 1A2, and 2B1 activities, were constructed by genetic engineering in continuation of our work to establish a battery of V79 derived cell lines designed to study the metabolism of xenobiotics. 2. Cell lines XEM1 and XEM2, expressing cytochrome P4501A1, were capable of the O-dealkylation of 7-ethoxycoumarin and the hydroxylation of benzo[a]pyrene. 3. Cell lines XEMd.MZ and XEMd.NH, expressing P4501A2, were shown to hydroxylate 17 beta-estradiol and 2-aminofluorene. 4. Cell line SD1, expressing cytochrome P4502B1, was able to hydroxylate testosterone stereo- and regio-specifically at the 16 alpha and 16 beta positions. 5. Cell lines were validated in mutagenicity, cytotoxicity, and metabolism studies employing benzo[a]pyrene, trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, cyclophosphamide, ifosfamide, and picene. 6. Construction of metabolically competent V79-derived cell lines be recombinant DNA technology will be a fundamental improvement for the evaluation of the cytotoxic, genotoxic and pharmacological properties of a chemical. PMID- 1441602 TI - Multiple mechanisms in hepatic microsomal azoreduction. AB - 1. Microsomal reduction of azo dyes related to dimethylaminoazobenzene (DAB) is catalysed by at least two types of cytochrome P-450. The first is selectively induced by clofibrate. The second is induced by phenobarbital, beta naphthoflavone, isosafrole, and pregnenolone-16 alpha-carbonitrile, as well as clofibrate. 2. Azoreduction by the first type of P-450 is insensitive to both O2 and CO and involves dyes with only electron-donating substituents (I substrates). 3. Azoreduction by the second type of P-450 is inhibited by both O2 and CO and involves dyes with electron-withdrawing as well as donating substituents (S substrates). 4. All azo dye substrates exhibit two negative and one positive redox potential, as measured anaerobically by cyclic voltammetry. The negative potentials reflect one- and two-electron reductions while the positive potential permits electron transfer from microsomal P-450, the redox potential for which is reported to be negative (approximately 0.35 V). The positive potential is associated with a polar electron-donating group para to the azo linkage, which is an absolute requirement for microsomal reduction. Dyes without this functional group do not exhibit positive potentials and are not reduced. 5. The first negative potential of S substrates is quenched upon admitting air to the system, whereas this potential is unaffected in I substrates. The relative stability of the one-electron reduced state may be an explanation for the differential O2 sensitivity of I and S substrate reduction. PMID- 1441603 TI - Metabolic activation of 1-nitropyrene to a mammalian cell mutagen and a carcinogen. AB - 1. The mutagenicity of 1-nitropyrene metabolites in Chinese hamster ovary (CHO) cells, in the absence of rat liver S9, decreased in the order 6-hydroxy-1 nitropyrene > 1-nitropyrene 9,10-oxide > 1-nitropyrene 4,5-oxide approximately 3 hydroxy-1-nitropyrene approximately 8-hydroxy-1-nitropyrene > 1-nitropyrene. The order of mutagenicity with rat liver S9 was 1-nitropyrene 4,5-oxide approximately 6-hydroxy-1-nitropyrene approximately 1-nitropyrene 9,10-oxide > 3-hydroxy-1 nitropyrene approximately 1-nitropyrene > 8-hydroxy-1-nitropyrene. 2. 1 Nitropyrene 4,5-oxide reacted with calf thymus DNA to give one or several closely related adducts. The same adducts were detected in CHO cells incubated with 1 nitropyrene 4,5-oxide. Inclusion of a nitroreductase, xanthine oxidase, in the incubations with calf thymus DNA resulted in the formation of an additional adduct identified as N-(deoxyguanosin-8-yl)-1-aminopyrene (dG-C8-AP). 3. 1 Nitropyrene 9,10-oxide reacted with calf thymus DNA to give an adduct pattern similar to that observed with 1-nitropyrene 4,5-oxide. Incubation of 1 nitropyrene 9,10-oxide with CHO cells resulted in the formation of the same adducts along with dG-C8-AP. 4. dG-C8-AP and N-(deoxyguanosin-8-yl)-1-amino-x nitropyrene (x = 3, 6 or 8; dG-C8-ANP) were detected in injection site DNA from Sprague-Dawley rats treated with 1-nitropyrene. In mammary gland DNA, dG-C8-AP and an unidentified adduct were found. dG-C8-ANP was the only DNA adduct detected in the livers of newborn CD-1 mice and the lungs of A/J mice dosed with 1 nitropyrene. PMID- 1441604 TI - Glutathione-dependent toxicity. AB - 1. Recent studies show that glutathione conjugate formation is an important bioactivation mechanism for several groups of compounds with implications for organ-selective toxicity and carcinogenicity. 2. Vicinal dihaloalkanes, such as 1,2-dihaloethanes, yield S-(2-haloalkyl)glutathione conjugates that give rise to highly electrophilic episulphonium ions, which are involved in the cytotoxicity and mutagenicity of 1,2-dihaloethanes. 3. Nephrotoxic haloalkenes are metabolized to S-(haloalkenyl)- or S-(haloalkyl)-glutathione conjugates which, after metabolism to the corresponding cysteine conjugates, are bioactivated by renal cysteine conjugate beta-lyase to yield cytotoxic or mutagenic metabolites. 4. Finally, hepatic glutathione conjugate formation with hydroquinones and aminophenols yields conjugates that are directed to gamma-glutamyltransferase rich tissues, such as the kidney, where they undergo alkylation or redox cycling reactions, or both, that cause organ-selective damage. PMID- 1441605 TI - The use of stable isotopes to identify reactive metabolites and target macromolecules associated with toxicities of halogenated hydrocarbon compounds. AB - 1. Halogenated compounds, such as the inhalation anaesthetics, halothane and enflurane, and the chemicals chloroform, carbon tetrachloride, and bromotrichloromethane can cause hepatotoxicity, nephrotoxicity, and inactivation of cytochromes P-450. Each of these toxicities is mediated by reactive metabolites. 2. Stable isotopes of hydrogen, carbon, chlorine and oxygen have been used in conjunction with mass spectrometry and n.m.r. spectrometry to identify the structures of these metabolites, to elucidate the mechanisms of their formation, and to characterize the structures of their macromolecular adducts. 3. In a number of cases, oxidative pathways of metabolism to toxic metabolites have been defined by kinetic deuterium isotope effects. 4. Recently, we have found that the trichloromethyl radical metabolite of bromotrichloromethane can activate myoglobin by causing the covalent cross linking of haem to protein. The structure of a haem-myoglobin adduct has been defined by the use of stable isotope studies. PMID- 1441606 TI - Investigations of mechanisms of reactive metabolite formation from (R)-(+) pulegone. AB - 1. (R)-(+)-Pulegone is a monoterpene that is oxidized by cytochromes P-450 to reactive metabolites that initiate events in the pathogenesis of hepatotoxicity in mice, rats and humans. 2. Selective labelling of (R)-(+)-pulegone with deuterium revealed that menthofuran was a proximate hepatotoxic metabolite formed by oxidation of the allylic methyl groups of pulegone. Incubations of pulegone with mouse liver microsomes in an atmosphere of 18O2 resulted in the formation of menthofuran that contained only oxygen-18 in the furan moiety. These results are consistent with oxidation of pulegone to an allylic alcohol that reacts intramolecularly with the ketone moiety to form a hemiketal that subsequently dehydrates to generate menthofuran. 3. Studies on the metabolism of menthofuran revealed that it is oxidized by cytochromes P-450 to an electrophilic gamma ketoenal that reacts with nucleophilic groups on proteins to form covalent adducts. In addition, diastereomeric mintlactones are formed. Investigations with H2(18)O and 18O2 are indicative of a furan epoxide intermediate, or a precursor, in the formation of the gamma-ketoenal and mintlactones. PMID- 1441607 TI - Deuterium isotope effect on the metabolism of N-nitrosodimethylamine and related compounds by cytochrome P4502E1. AB - 1. Deuteration of N-nitrosodimethylamine (NDMA) decreases its carcinogenicity, and produces an isotope effect on its metabolism in vivo. Consistent with these results are the observations that deuteration caused a 5-fold increase in the apparent Km, but not the Vmax for the demethylation and denitrozation of NDMA in acetone-induced rat liver microsomes. These microsomes are a good source of cytochrome P4502E1. 2. For demethylation of Z-[2H3]NDMA and E-[2H3]NDMA, the Km values were indistinguishable, and were between the values for those of NDMA and [2H6]NDMA. Almost all the formaldehyde formed was derived from the non-deuterated methyl group, indicating a lack of stereoselectivity in the demethylation of NDMA. 3. NDMA and [2H6]NDMA displayed apparent Ki values of 59 and 441 microM, respectively, for N-nitrosodiethylamine deethylase, showing an apparent isotope effect of 0.13, and displayed an isotope effect of 0.21 in the Ki values for p nitrophenol hydroxylase. 4. With acetone and deuterated acetone as inhibitors for p-nitrophenol hydroxylase, the isotope effect on the Ki was 0.11. Similar deuterium isotope effects were also observed with acetone and dimethylformamide as competitive inhibitors for NDMA demethylase. 5. In the microsomal oxidation of ethanol, a deuterium isotope effect of about five was observed in the Vmax/Km when carbon-1 was deuterated, but was not observed in the Vmax. 6. Results illustrate a unique deuterium isotope effect on the Km values of reactions catalysed by P4502E1. PMID- 1441608 TI - The role of the flavin-containing monooxygenase (EC 1.14.13.8) in the metabolism and mode of action of agricultural chemicals. AB - 1. The flavin-containing monooxygenase (FMO) (EC 1.14.13.8) is a versatile enzyme that catalyses the monooxygenation of a large number of xenobiotic soft nucleophiles ranging from inorganic ions to organic compounds with nitrogen, sulphur, phosphorus or selenium heteroatoms. 2. The substrate specificity relative to agricultural chemicals is discussed and compared with that of the cytochrome P-450-dependent monooxygenase system. The relative activity of these two enzymes towards common substrates varies from substrate to substrate and from tissue to tissue as is shown in the case of the insecticide, phorate and the hepatotoxicant, thiobenzamide. 3. The products of FMO action may be chemically different (e.g. nicotine) to those from P-450, or the two enzymes may produce different isomers of the same product (e.g. phorate). 4. Recent studies have demonstrated that, in the rabbit, the FMOs from liver and lung are different gene products which differ not only in primary sequence but also in physical, catalytic and immunochemical properties. These studies are being extended to include other tissues such as skin and brain. 5. Immunocytochemical localization of FMO in lung and skin correlates well with measurements of the oxidation of methimazole, a specific FMO substrate. PMID- 1441609 TI - Metabolic considerations in pyrethroid design. AB - 1. Synthetic pyrethroids, based on the naturally-occurring insecticidal components of pyrethrum extract, emerged in the 1970s as the fourth major chemical class of synthetic insecticides. They are widely used today in the control of agriculture and household pests and disease vectors. 2. Early efforts in the design of synthetic analogues focused on the need to identify novel structural moieties that preserved or enhanced intrinsic insecticidal activity while eliminating known sites of metabolic and photolytic attack in the natural compounds. Subsequent efforts focused on achieving high levels of insecticidal activity while minimizing costs of synthesis and retaining desirable levels of selective toxicity. 3. The synthetic compounds obtained in these efforts constitute a group of insecticides having unprecedented biological activity against target species with low acute toxicity to mammals. 4. The evolutionary development of the pyrethroids illustrates how knowledge of metabolic fate can contribute to the design of novel insecticides with improved insecticidal activity and selective toxicity. PMID- 1441610 TI - Bioanalytical data in decision making: discovery and development. AB - 1. Bioanalysis is traditionally associated with the development phase of drugs; its use in discovery programmes is often ignored but can have a major impact. 2. Pharmacokinetic studies conducted in conjunction with pharmacology screening can provide additional information to that considered in conventional structure activity relationships. Such factors as half-life and bioavailability can be critical in designing improved drugs. 3. Analytical methods in discovery programmes may differ from those used in later development work: for instance bioassay allows a common assay system for a large number of project compounds. Moreover its use, when combined with conventional methods, such as h.p.l.c., allows active metabolites to be readily detected. 4. Bioanalytical data generated in discovery and pre-clinical programmes are a valuable guide to early clinical programmes. Plasma concentration-response data from these programmes can be compared with those obtained in man. Such comparisons are particularly valuable during the phase one-initial dose escalation study. To maximize this it is our practice to generate pharmacokinetic data between each dose increase. PMID- 1441611 TI - High-performance tandem mass spectrometry in metabolism studies. AB - 1. High-performance tandem mass spectrometry provides unit resolution in both selection of precursor ions and analysis of fragment ions, and extensive and reproducible fragmentation through collisional activation at high energy. 2. Metabolites can be analysed that occur as minor components in h.p.l.c. peaks or other mixtures. Homogeneous isotopic species can be selected for unambiguous analysis of distributions of isotope labels. Fragmentation may be significantly enhanced to provide structural information. Overall, the signal to noise ratio is greatly improved and the spectrum is simplified. 3. These points are illustrated by isotope-labelling studies of the mechanisms of glutathione conjugation of the anti-tumour agent cyclophosphamide, the cytotoxic agent phosphoramide mustard and dimethylbilirubin, an analogue of bilirubin designed to be distinguishable from endogenous bilirubin. Analysis of isomeric mixed disulphides formed between glutathione and a peptide with an internal disulphide bond is discussed. 4. Reaction-induced decomposition is presented as an alternative to collisionally induced decomposition with more efficient energy transfer. PMID- 1441612 TI - [13th Symposium for attorneys and physicians, 11 and 12 January 1991 in Berlin. Expert assessment in forensic psychiatry. Geriatric psychiatry]. PMID- 1441613 TI - [Expert assessment in legal liability--from the physician's viewpoint]. PMID- 1441614 TI - [Expert assessment in criminal justice--from the legal viewpoint]. PMID- 1441615 TI - [Expert assessment in civil rights. Determination of working capacity--from the physicians viewpoint]. PMID- 1441616 TI - [Expert assessment in civil rights. Determination of work capacity--from the legal viewpoint]. PMID- 1441617 TI - [Expert assessment in civil rights. Determination of informed consent--from the legal viewpoint]. PMID- 1441618 TI - [Expert assessment in social law. Determining need for care--from the legal viewpoint]. PMID- 1441619 TI - [Expert assessment in social law. Determination of the need for care--from the physician's viewpoint]. PMID- 1441620 TI - [Expert assessment in social law. Determining the need for nursing care--from the socio-political viewpoint]. PMID- 1441621 TI - [Expert assessment in social law. Expert assessment of neuroses and psychosomatic disorders--from the physician's viewpoint]. PMID- 1441622 TI - [Expert assessment in social law. Expert assessment of neuroses and psychosomatic disorders--from the legal viewpoint]. PMID- 1441623 TI - [The significance of psychiatry for geriatrics]. PMID- 1441624 TI - [Ability to give legal testimony--from the physician's viewpoint]. PMID- 1441625 TI - [Ability to give legal testimony--from the legal viewpoint]. PMID- 1441626 TI - [Legal guardians--disability--management--from the physician's viewpoint]. PMID- 1441627 TI - [Legal guardians--disability--management--from the legal viewpoint]. PMID- 1441628 TI - [Diagnosis using the ear?]. PMID- 1441629 TI - [Phototherapy of skin diseases]. PMID- 1441630 TI - [Ultrasonic diagnosis of cholangiolithiasis]. PMID- 1441631 TI - [Are introverted probands positively effected by piroxicam?]. PMID- 1441632 TI - [Differential diagnosis of psoriatic arthritis (osteoarthropathia psoriatica) and chronic polyarthritis (rheumatoid arthritis)]. PMID- 1441633 TI - [Prevention of thromboembolism with heparin and dihydroergotamine in a trauma surgery patient sample--comparison of the effectiveness of different administration forms of dihydroergotamine]. PMID- 1441634 TI - [Immunocytologic tumor cell detection in bone marrow of breast cancer patients]. PMID- 1441635 TI - [42-year-old patient with fever and weight loss of unknown origin]. PMID- 1441636 TI - [Infectious diseases in the elderly]. PMID- 1441637 TI - [Bacterial infections of the liver in the elderly]. PMID- 1441638 TI - [Value and results of trans-sphenoid surgery of the hypophysis in acromegaly]. PMID- 1441639 TI - [Nutritional references for patients with migraine or headache]. PMID- 1441640 TI - [Rapid cycling syndromes in adolescence]. PMID- 1441641 TI - [Histologic changes of the myocardium after heart transplantation]. PMID- 1441642 TI - [A case report from general practice (1): pale appearance and dyspnea]. PMID- 1441643 TI - [Pharmacotherapy in the elderly]. PMID- 1441644 TI - Salmonellosis--a cause of concern and a challenge. PMID- 1441646 TI - [Energy balance in repeated under- and overnutrition in model studies in sows]. AB - In a model experiment eight adult sows were used to examine the effect of successive periods of under- and oversupply of energy (MUMU) on thermogenesis and efficiency of energy utilization in comparison to a constant maintenance supply (NNNN). Each treatment sequence was assigned to each animal according to a change over design over 8 weeks. Before and after the treatment periods all the animals were fed at maintenance level (N). Energy deficiency (M) was performed by use of a basal diet with 45% of maintenance energy requirements and values for all the other nutrients sufficient for requirements. Normal (N) and excessive (U) intakes of energy was provided with supplements of starch. The total inake of gross energy during the periods MUMU was exactly the same as during NNNN. Complete energy balances were performed for each animal and period as well as during the pre- and post-experimental phase. There was no or little response of altered energy intake on carbon and energy excretion in faeces, urine and methane. However, heat production was significantly decreased by 4.1% on energy deficiency, and increased by 15.1% during energy oversupply. Summed up over the total sequence the animals produced 5.4% more heat on MUMU than during NNNN. This response was associated with a mobilization of 1.1 MJ/d tissue energy and a decrease in body weight by 2.0 kg. The efficiency of utilization of ME was 88% with energy undersupply and 75% during overnutrition. Criteria of energy balance did not differ between the pre- and post-treatment periods. It could be demonstrated that the increase in energy expenditure at oversupply was entirely explainable by the so-called obligatory thermogenesis. At the energy deficiency periods the efficiency of energy utilization reflected both energy costs of ingestion and processing of nutrients as well as a slight reduction in metabolic rate. Finally, there were no residual effects of the treatment on the energy expenditure of the animals at the end of the experiment. PMID- 1441645 TI - Citrinin. AB - Citrinin, a nephrotoxic mycotoxin, has been of growing importance also for the "International Agency for Research on Cancer", ever since its presumable role in the occurrence of Balcan endemic nephropathy (BEN) was discussed at the congress on "Mycotoxins, Endemic Nepthropathy and Urinary Tract Tumours" held in Lyon in June 1991 (12). In late 1991, citrinin was therefore also included in the list of toxins to be examined by the screening subcommittees on natural toxins of the International Live Science Institute, European Branch. PMID- 1441647 TI - [The nutrition situation of the population in the former East Germany: results of household budget surveys in 1989]. AB - The last representative nutritional surveys in households of the former GDR date back to 1989. Trends towards excessive energy intake have continued, resulting, above all, from high fat consumption. A considerable proportion of employed persons have their meals outside the home. The proportion of food used as animal feed was high in households of members of agricultural cooperatives. PMID- 1441648 TI - [Intake of trans-isomeric fatty acids--an evaluation on the basis of data of the national consumption study in 1991]. AB - The intake of trans octadecenoic acids is estimated by a national consumption assay. The daily intake in West Germany differs between 3.4 g for women and 4.1 g for men. The consumption of trans fatty acids decreased in the last years, due to the progress in food technology and changes in nutritional habits. The main sources of trans fatty acids are partially hydrogenated vegetable fats just as well as ruminant and dairy fats. PMID- 1441649 TI - [Common attitudes about the effect of positive and negative mood on task related motivation]. AB - Several theories on emotion and mood have stressed the close relationship between emotion and motivation. However, assumptions on mood contingent motivations have mainly been studied in the field of social behavior, and there are only few studies concerned with mood contingent task motivations, an area in which nit is possible to distinguish between two motivational sets, the deliberative and the implemented mind set. Assuming that positive mood is associated with a stronger task-oriented deliberative mind set, and that negative mood is associated with a stronger self-oriented deliberative mind set, and that implemented mind set should be intrinsically task-oriented during positive mood and instrumentally task-oriented during negative mood. The present paper is concerned with these assumptions from a subjective perspective: The respondents were asked about their lay perceptions of mood influences (positive, elated versus negative, sad mood) on task related motivations. In study I the respondents (N = 40) were asked about their deliberative mind sets during positive versus negative mood and about their general perceptions of mood influences on performance. In study II the respondents (N = 58) were requested to imagine situations which elicit positive, negative or neutral mood, and then to answer questions on deliberative and implemented mind sets during these states; they also hat to answer a general question about mood influences on task performance. Both quantitative and qualitative measures are used in these studies. The findings support the above general notions, and they additionally show that in the respondents' opinions negative mood effects are more variable than positive mood effects; further, that there are quite a few individual differences in assumed mood effects on task related motivation. PMID- 1441650 TI - [Slow alpha in the EEG power spectrum as an indicator for conceptual arousal]. AB - Based on previous findings (Bosel et al., 1990) it was assumed that in concept learning tasks generating on hypotheses on a concept which has to be developed is accompanied by increases of the Alpha 1 power (7.5-10 Hz) in the spontaneous EEG activity. In this study 16 subjects performed five problem solving tasks with similar processing requirements. EEG data were analyzed by means of post hoc comparisons of subjects differing in performance quality. Additionally, four control tasks were employed in which, based on previous studies, variations in the Theta frequency range were expected. An effect in the Alpha 1 frequency band was observed in tasks requiring reconstructive recall or testing the usefulness of an mathematical algorithm. The creation of a rank order or mental map is accompanied by power increases in the lower portions of the Alpha 1 frequency band (7.5-8.5 Hz). Moreover a high amount of controlled variance (eta2 up to 34%) was obtained for this effect. Increases in EEG Theta power, which presumably indicate subjects' component analysis, were found before the subjects recognized parts of geometric figures or before relevant features in the "buddhist monk problem" were discriminated. The dynamics of EEG power over time is in examples of frequency/time plots in a figure, illustrated. PMID- 1441651 TI - [The correlation between coping with stress and blood pressure reaction]. AB - This study explored the relationship between individual strategies of coping and blood pressure responses during and after mental stress. Blood pressure behavior was measured noninvasively and continuously before, during and after a mental stress situation in 27 normotensive subjects. Coping strategies were assessed with the Stressverarbeitungsfragebogen (SVF; coping with stress inventory). Two extreme groups were formed on the basis of the scores in the SVF. Results were: (a) Individuals who used coping strategies characterized by controlling the situation directly and constructively, in contrast to probands not using these strategies, exhibited lower blood pressure during the stress situation and a faster return to baseline levels after cessation of stress. (b) Subjects using a coping behavior characterized by the use of defense mechanisms such as suppression and denial, also showed lower blood pressure during stress but a significantly delayed return to baseline levels of blood pressure after stress was concluded. PMID- 1441652 TI - [EMG reactions of mimetic muscles after repeated presentation of pictures with positive, negative and neutral content]. AB - Twenty male subjects (Ss) were repeatedly confronted for five seconds to pictures with positive, negative and neutral valence. During the picture presentation facial EMG-reactions of five mimic muscles (m. frontalis lateralis, m. corrugator supercilii, m. orbicularis oculi, m. zygomaticus major on the right and left side of the face) were recorded. In addition, heart rate was measured. It could be shown that during repeated presentation of pictures with positive valence the m. orbicularis oculi and the m. zygomaticus major on both sides of the face yielded enhanced average EMG-reactions as compared to the repeated presentation of pictures with negative and neutral valence. During presentation of pictures with negative valence the m. frontalis lateralis and the m. corrugator supercilii revealed enhanced EMG-reactions as compared to the repeated presentation of pictures with positive valence. Furthermore, it could be shown that during the repeated presentation of pictures with positive valence those facial muscles which mainly react during confrontation with pictures of positive valence showed a continuous decrease of EMG-activity. Facial muscles which mainly react during the presentation of pictures with negative valence do not show a continuous decrease in EMG-activity during the course of the repeated presentation of pictures with negative valence. Additionally, the EMG-activity of the m. zygomaticus major on the right and lift side of the face do not differ with respect to the mean activity and the time course during confrontation of pictures with positive valence. The m. orbicularis oculi yielded enhanced EMG-reactions during the presentation of pictures with positive valence as compared to both m. zygomaticus major muscles. The present results are discussed with respect to psychobiological theories concerning facial expression. PMID- 1441653 TI - [Change in the event-related skin conductivity: an indicator of the immediate importance of elaborate information processing?]. AB - In recent psychophysiological conceptualizations of the orienting response (OR) within the framework of information processing, the OR is increasingly considered a "call for processing resources", something which is especially inferred from variations in the event-related skin conductance response (SCR). The present study, therefore, was concerned with certain implications arising from this framework or perspective, particularly in regard to the question of whether stimuli eliciting skin conductance responses obligatorily receive/evoke processing priority or not. In order to examine whether these electrodermal responses denote a capturing of attention or merely a call for processing resources, short (1 s) pure sine tones of 65 dB with sudden onset (commonly used as orienting stimuli) were inserted in a reaction time paradigm with an additional memory load. This demand was primarily given because memory processes play a key role in theories of orienting and habituation. The task was run under two different conditions of complexity, factorially combined with a novelty variation of the added auditory stimuli. The results revealed a substantial deterioration of task performance subsequent to the occurrence of the tones, which, however, was dependent on task complexity and on novelty of the tones. The task impairment is particularly remarkable as subjects were asked to avoid distractions by paying attention to the task and as the tones were introduced as subsidiary and task-irrelevant. Together with the missing effects of task complexity on phasic and tonic electrodermal activity, results suggest that information-processing conceptualizations of the OR can only be a meaningful heuristic contribution to theoretical developments about human orienting and its habituation if the setting of processing priority, its conditions, as well as its implications are adequately taken into account. In addition, it seems to be promising to consider the strength of the SCR as an index of urgency of elaborate, attention-demanding processing and not as a peripheral physiological manifestation of the OR, or, respectively, of a call for unspecific processing resources. Such a view would also do justice to the aspect of prioritization. The sufficient conditions for an OR's occurrence could, in this context, be equated with, among others, some of those which activate a mechanism subserving selective attention and, as a possible result, which lead to further and more elaborate processing of potentially important information. PMID- 1441654 TI - [Life expectancy]. PMID- 1441655 TI - [Gene technology in production of modern drugs]. AB - In the last years gene technology has influenced dramatically medical and biological disciplines. With the help of molecular biology it is possible to produce a variety of proteins in alternative ways. Further, substances can be produced which exist in nature only in trace amounts, and therefore can not be produced with conventional methods. However, there is no other scientific discipline which is discussed so controversially in public like genetic engineering. The "new" biology comprises a multitude of disciplines which are difficult to understand for non experts. Unfortunately, gene technology has become the new symbol for "uncontrolled" technology development. In this review article the basic concepts of genetic engineering will be explained. Further, the production of some recombinant drugs, which are already used in practice, will be demonstrated. Finally, some safety aspects concerning about risk assessment are discussed. PMID- 1441656 TI - [Therapy of acute lung failure with nifedipine. A study with interventional analysis]. AB - In 24 patients with severe ARDS after major gastro-intestinal surgery the effect of the calcium antagonist nifedipine on pulmonary function was investigated. Besides descriptive statistics and comparison between group means, intervention analysis was employed to assess the treatment effect for the individual patient. The treatment effect could always be assessed after 12 hours. 14 out of 15 patients with initially high PVR showed a significant decrease of PVR followed by an improvement of AaDO2. 8 out of 9 patients with initially normal PVR did not improve in pulmonary function as no significant changes in PVR occurred. No unwanted side-effects on cardio-vascular function (MAP, CI, LVSWI, RVSWI) could be observed. 9 out of 24 patients decreased. Lethality among patients who showed a significant decrease of PVR under nifedipine infusion was 3 out of 15, whereas 5 out of 9 patients died without changes in PVR. Thus nifedipine can improve pulmonary function in ARDS. Especially in the early stages of ARDS with elevated PVR the administration of nifedipine p.i. appears advantageous. PMID- 1441657 TI - [Clinical and hemodynamic results of surgical correction of hypertrophic obstructive cardiomyopathy]. AB - The value of transaortal subvalvular myectomy after Morrow remains unclarified. We therefore analysed our results with HOCM with particular attention to the operation risk and the longterm results. 56 patients were treated at the Leipzig Heart Centre between January 1984 and August 1990 using the transaortic myectomy. In 16 patients an additional mitral valve replacement or -reconstruction was required. In 14 patients, other combined operations (aortic valve replacement, aortocoronary bypass) were indicated. In the postoperative observation period (up to 7 years; 141 patient-years; mean follow-up 4.2 yrs) detailed information was obtained at regular intervals about subjective complaints, ECG changes, left ventricular functional parameters and the weight of the heart muscle mass were recorded. The myectomy resulted in an alteration of the NYHA-class from 3.1 to 1.3 postoperatively (p < 0.05). The ventriculo-aortal pressure gradient reduced in the group myectomy (group I) from 69.2 +/- 5.2 to 23.3 +/- 2.7 mmHg postoperatively. In the myectomy+mitral valve repair group (group II) the intracavitary pressure gradient was even reduced to 11.7 +/- 2.2 Torr (p < 0.05). The Sokolov-Lyon-Index was 3.7 +/- 0.19 mV preoperatively and went down to 2.9 +/ 0.16 mV. The heart muscle mass decreased from 680 g to a postoperative value of 430 g (p < 0.05). The relation of BAR and calcium channel density of 0.5 +/- 0.1 in HOCM versus 0.9 +/- 0.08 in a control group (n = 6) proves the increased number of calcium channels in HOCM. PMID- 1441658 TI - [The quality of life of the aged after heart surgery interventions. Analysis of a patient sample of very advanced age]. AB - Due to the continual improvement of surgical and anaesthesiological techniques, the cardiac patients are now of a much higher age than was previously the case. Only pre- and postoperative comparison of life quality can show in what manner these old patients are improved by cardiac surgery. 71 patients with the mean age of 77.6 years were examined by standardized interviews at hospital admittance and one year after returning home. Although there was no statistical significance, there was a very clear trend towards improved quality of life. These very good long-term results concerning the quality of life justify an increased operative risk in this group of 70-80 years old patients. In our study we could show results which were as good as has been shown with younger patients in literature. PMID- 1441659 TI - [Depression in general practice of the internist and family physician]. AB - Successful approach to depressed patients demands some knowledge of psychopathology, nosology and psychopharmacology. Some important aspects for practitioners of understanding and coping with depressives are given. An overview on the role of antidepressants (TCAs, selective serotonin re-uptake inhibitors, MAO-inhibitors) is also given. PMID- 1441660 TI - ["Rejuvenation" as the outcome of research on aging: dreams and theories- experiments and results]. AB - A report is given on experiments of rejuvenation which were carried out in the first decenniums of the 20th century. The knowledge of the effect of sexual hormones on the one hand and still missing possibilities of synthesisation on the other gave rise to spectacular transplantations and further operation techniques as well as physical forms of therapy on testicles and ovaries. The fundaments of the scientific theory and the social backgrounds of these side branches of gerontology which established itself only at the end of the thirties are mentioned. PMID- 1441661 TI - [Conventional roentgen functional diagnosis--videodensitometry. 1. Densitometric and topometric measurements of roentgen video images: technique and method of measuring]. AB - It is possible to measure movements in the human body with the help of X-ray television systems. A great number of different techniques has been published in the scientific literature. They all based on only two principles with qualitative differences in signal acquisition. The densitometric and topometric measurements are assessed and compared. Neither the densitometric nor the topometric principle seems to be superior. To support the experimental work the videoanalyser VIANA MP was developed on the Ilmenau Institute of Technology. PMID- 1441662 TI - [Conventional roentgen functional diagnosis--videodensitometry. 2. Clinical imaging site for noninvasive diagnosis of organ motion]. AB - By means of the described system it is possible to measure and as well analog as digital process the organ movement, needing a X-ray television system for flouroscopy and a videotape for continuously recording. Using the densitometric principle measurements of time and a quantitative form analysis of the curves are performed. After border recognition and using the topometric principle, the local organ motion can be evaluated. The levels of signal and noise in the measured curves are computed by a fourier transformation. In the field of functional cardiology the video signal is recorded and processed synchronously with the electrocardiogram. PMID- 1441663 TI - [The physician's responsibility for patient education. Part I]. PMID- 1441664 TI - [Treatment with antibacterial chemotherapy]. AB - The importance of a true indication of antimicrobiological chemotherapy is discussed on beginning of the paper. A correct choice of antibiotics and proper strategy of therapy will be demonstrated. Additionally essential antibiotics are presented. PMID- 1441665 TI - [Current status and change in infectiology]. AB - Clinical infectiology had passed through a marked transformation in the past, it is changing in the present time and will do so in the future. The most important factors for these changes are: the change of the living standard of the people, the increased number of persons with dispositions for infections, a better knowledge about the microbial etiology of infections and new possibilities of diagnostics and therapy of infectious diseases. The importance of these changes are in Germany inadequately reflected not only in the clinical practice but also in medical teaching and research. The reintegration of the infectiology as an important medical specialty in the Germany's medicine is urgently indicated. PMID- 1441666 TI - [Clinical microbiology as a basis of antimicrobial chemotherapy]. AB - Clinical microbiology is a facet of medical microbiology which is dedicated to all aspects of human infectious disease diagnosis, especially in patients treated in hospitals. The specific tasks of such a laboratory can be solved at best, if it is integrated in the hospital and if there is close co-operation with clinical specialists. Different methods for susceptibility testing of isolated bacteria are possible: agar diffusion test, agar dilution test, bouillon dilution test etc., the results of which need to be interpreted considering further aspects. During antimicrobial chemotherapy certain tests are also necessary or useful. The objective of future developments is to avoid the need of cultures and to establish antibiotic profiles within hours to provide the clinician with relevant results. PMID- 1441667 TI - [Antibiotic therapy of bacterial respiratory tract infections]. AB - Infections of the airways are among the most frequent of inflammatory diseases appropriate for antibacterial therapy. One must differentiate between infections of the upper and lower airways, respectively infections obtained externally, and nosocomial infections. Since a relatively uniform spectrum of microbes can usually be expected, well-planned antibacterial therapy is possible. For nosocomial infections, on-target antibacterial therapy is required. For the various diseases of the airways, diagnostic and therapeutic strategies are outlined. PMID- 1441668 TI - [Diagnosis and therapy of urinary tract infections]. AB - Urinary tract infections (UTI) are one of the most frequent indications for antibacterial chemotherapy. We must be differentiate between complicated and uncomplicated as well as between upper and lower UTI. Regarding the definition of significant bacteriuria (> or = 10(5) CFU/ml), some relativations are necessary. Dip-slide techniques proved to be very useful for bacteriological diagnosis. The calculated therapy depends upon age and sex and is different for community acquired and nosocomial infections. Further items are the selection of antibacterial agents, the duration of chemotherapy, the role of asymptomatic bacteriuria and reinfection prophylaxis. PMID- 1441669 TI - [Antimicrobial chemotherapy of infection in intensive care conditions]. AB - Antimicrobiologic chemotherapy is a cornerstone in the modern concept of treatment of sepsis. It is supported by a number of measures of intensive care. Externally acquired infections followed by sepsis mainly affect immunocompromised patients. They represent the minority. On the other hand, nosocomial infections play a dominant role in intensive care units. Nosocomial pneumonias and infections caused by intravascular plastics or endoprotheses are the most important reasons of sepsis. Initial antimicrobiologic therapy considers both the infectious focus and the specific epidemiology and resistance of microorganisms present in the department: it comprises the drawing of 2 to 3 blood cultures, taking of urinary cultures, tracheal secretion, liquor and wound-swaps for microbiologic examination. A gramstaining of the preparation can be helpful. In case the focus of the sepsis is not known, the first step of treatment consists of a combination of piperacilline or cephalosporins with aminoglycosides. If the septic state does not improve within 48 hours, a glycopeptide should be added against staphylococci (second step). If the combination fails, imipenem/cilastatin and aminoglycosides are administered as the third step. Normally, the result of cultures and resistogram already are available by this time. Today aminoglycosides are preferably given once daily, the serum level is monitored, and the toxicity of aminoglycosides is thus diminished. PMID- 1441670 TI - [Therapy of bacterial infections in neutropenic and immunocompromised patients]. AB - Neutropenias, especially extended an long-lasting stages, lead to life threatening endogenous infection. Therefore, after taking off materials for bacteriological investigations an empirical schedule of a combined high dose, treatment with broad-band antibiotics and/or antimycotics has immediately to be introduced and to continue until the body temperature and the peripheral blood granulocytes are normalized. In case of treatment failure one should complete the therapy by other additional antibiotics or correct the combination of its in respect to the results of the microbiological investigations. Supplements of this antimicrobial treatments are immunoglobulins and growth factors (G-CSF, GM-CSF). In case of an expected neutropenica the use of the selective gut decontamination or the reverse isolation of the patient can be of essential advantage. PMID- 1441671 TI - [Fungal infections in granulocytopenic and immunocompromised patients]. AB - Opportunistic fungus infections in neutropenic immunocompromised patients have strikingly increased, especially with the improvement of antibiotic treatment. Their outcome is often fatal because of the difficulties in diagnosis and treatment. Therefore a rationale of surveillance diagnostics and empiric treatment in risk patients is necessary. In these patients a continuous weekly mycotic diagnosis of mouth, throat, faeces, urine, vagina, as well as of the blood is necessary. During an aggressive neutropenia-producing chemotherapy an antimycotic prophylaxis with the aim of reducing fungal colonization in the gastrointestinal tract (sometimes in the respiratory pathways, too) should be performed. Fever of unknown origin lasting longer than 4-5 days in spite of broad spectrum antibiotic treatment and/or positive diagnostic findings must lead to treating risk patients empirically using amphotericin B 1 mg/kg/d or a combination of amphotericin B 0.3-0.5 mg/kg/d together with flucytosin (Ancotil) 150 mg/kg/d. In case of a beginning candidiasis, patients can first be treated with fluconazol (Diflucan). The dose is 400 mg/d, later on 200 mg/d. It is pointed out that, much more often than usual, in risk patients with fever, atypical pneumonia, meningoencephalitis or other organ symptoms fungal infections should be taken into consideration. The most common opportunistic fungal diseases are presented and details concerning the different antimycotic drugs are given. PMID- 1441672 TI - [The value of ultrasound and computerized tomography in detection of cystic changes in chronic pancreatitis]. AB - Intra- or extrapancreatic pseudocysts (PP) are the most common local complication in chronic pancreatitis. Aim of this study was to investigate frequency, localisation and size of pseudocysts in patients with chronic pancreatitis by means of ultrasound (US) and computed tomography (CT). 155 patients (females 35, males 120) with chronic pancreatitis, that underwent simultaneous (within two weeks) CT and US examinations, from January 1982 to June 1989, were included in this study. Cystic lesions were detected in 62% by CT, in 52% by US. Sensitivity in detection of cysts based on intraoperative findings (gold standard) was 98% for CT and 94% for US. 80% of the pseudocysts were smaller than 6 cm. 46% were in the range from 2 to 66 cm and 34% were smaller than 2 cm. The most common localisation was the pancreatic head region (50%), 20 of 102 patients with chronic pancreatitis were found to have a direct communication of a pseudocyst with the ductal system by ERP. No specific clinical or laboratory pattern were associated with the presence of pseudocysts. Increased pancreatic serum amylase concentration was detected in 29% of patients with and in 27% of patients without pseudocysts. PMID- 1441673 TI - [Results of conventional and laparoscopic cholecystectomy]. AB - We report about a retrospective study of 861 conventional and 812 laparoscopic cholecystectomies (including one coelioscopic choledocholithotomy). In the conventionally operated group reoperation was required in 2.7% (1.4% relaparotomy, 1.3% secondary suture), mortality was 0.5%. After laparoscopic treatment the reoperation rate was 2% (10 relaparoscopies, 5 laparotomies, 2 secondary sutures), no mortality. Growing experience and better definition of contraindications for endoscopic cholecystectomy might improve our results in the future. PMID- 1441674 TI - [Therapy of stomach ulcer--a comparison between the low dosage antacid hydrotalcite and ranitidine--results of a randomized multicenter double-blind study. Talcivent Study Group]. AB - In a 8 week double-blind randomized multicenter trial in 159 patients with benign gastric ulcer the efficacy of hydrotalcite vs. ranitidine in expediting ulcer healing and in achieving pain relief was determined. 79 patients received hydrotalcite 1000 mg q.i.d. as tablets equalling a total neutralizing capacity of 111.2 mval and 80 patients received ranitidine (300 mg at night). Endoscopically controlled healing rates after 4 weeks of therapy amounted to 41.8% with hydrotalcite and 53.8% with ranitidine. After 8 weeks both regimen showed significant equivalent healing rates (hydrotalcite: 81.0%, ranitidine: 78.8%, p < 0.003). Ulcer pain decreased parallel in both groups. By the end of therapy 92.4% of the patients treated with hydrotalcite and 86.3% of those receiving ranitidine were free of pain. Incidence of helicobacter pylori in antral mucosal biopsies was not influenced by both treatments. We conclude that an 8-week treatment with low dose hydrotalcite therapy is as effective as ranitidine in healing benign gastric ulcers and achieving pain relief. PMID- 1441675 TI - Enteric protein loss as a marker of intestinal inflammatory activity in Crohn's disease: comparability of enteric clearance and stool concentration of alpha-1 antitrypsin? AB - Intestinal alpha 1-antitrypsin (alpha 1-AT) clearance has been shown a reliable index of intestinal inflammatory activity in Crohn's disease (CD). For reasons of practicability, it has been repeatedly suggested to replace alpha 1-AT clearance by alpha 1-AT concentration in random stool samples. In 60 controls and in 70 patients with CD, in 21 patients before and after treatment, fecal alpha 1-AT concentration and the ratio of stool and serum alpha 1-AT concentration were compared with alpha 1-AT clearance. In 11 patients alpha 1-AT clearance, fecal concentration and stool/serum alpha 1-AT concentration ratio were compared with 51Cr-albumin clearance. alpha 1-AT clearance (104 +/- 14 vs. 17.5 +/- 2 ml/d, p < 0.0001) as well as fecal alpha 1-AT concentration (155 +/- 21 vs. 30 +/- 3 mg/100 ml, p < 0.0001) and stool/serum alpha 1-AT concentration ratio (45 +/- 6 vs. 12 +/- 1) were significantly higher in CD patients than in controls. alpha 1-AT clearance (60 +/- 9 vs. 37 +/- 4 ml/d, p < 0.01), fecal alpha 1-AT concentration (113 +/- 21 vs. 59 +/- 8 mg/100 ml, p < 0.01) and the stool/serum alpha 1-AT concentration ratio (27 +/- 4 vs. 18 +/- 2) decreased after treatment, but fecal alpha 1-AT concentration and the stool/serum alpha 1-AT concentration ratio failed to parallel the course of alpha 1-AT clearance in 33% and in 24% of patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441676 TI - Active autoimmune gastritis without total atrophy of the glands. AB - To date, autoimmune gastritis has been diagnosed for the most part only when total atrophy of the oxyntic glands is detected. On the basis of 40 patients without total atrophy of the glands, and with parietal cell antibodies in the serum, we show that the diagnosis of type A gastritis is also possible in the pre atrophic stage. The histological criteria for the diagnosis of active autoimmune gastritis without total atrophy of the glands are 1. usually dense, diffuse locally emphasized lymphocytic infiltration of the lamina propria between the glands in the oxyntic mucosa, 2. focal destruction of individual glands in the corpus of the stomach by lymphocytes, and 3. reactive pseudohypertrophy of the parietal cells. A comparison with a group of patients with autoimmune gastritis and total atrophy of the glands shows that in active autoimmune gastritis, too, women are more frequently affected than men (in both groups, the sex ratio is approximately 3:1). Patients without atrophy of the glands are, on average, about 12 years younger than those with "burnt out" type A gastritis (average age 69.98:57.80 years). While in the case of burnt out type A gastritis, no colonisation with Helicobacter pylori was to be found, such colonisation was demonstrated for the corpus mucosa in 22.5%, and for the antral mucosa in 15.0%. In 27.5% a minimal or low-grade inactive superficial gastritis, as may be seen after eradication of Helicobacter pylori, was additionally diagnosed in the antrum. A knowledge of the histological appearance of the pre-atrophic stage of type A gastritis might be of importance for the possible prevention of pernicious anaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441677 TI - [Diffuse cholangiofibromatosis--incidental findings in sonography, ERCP and laparoscopy]. AB - Diffuse cholangiofibromatosis is a rare and asymptomatic abnormality. Its clinical significance results from problems that occur in differential diagnosis to granulomatous hepatitis, sclerosing cholangitis, multiple microabscesses or diffuse tumour infiltration of the liver, when it is incidentally found in ultrasound, ERCP or laparoscopy. The characteristic findings in these examinations are described in two case reports. The ultrasonic pattern of multiple intrahepatic double structures, microcystic areas and surrounding hyperechoic reflexes are in accordance with multiple intrahepatic microcystic and hazy areas in ERCP x-rays and multiple white-yellowish areas that retract liver surface in laparoscopy. Final diagnosis is confined by the characteristical microscopic finding of von Meyenburg-complexes in liver biopsy. PMID- 1441678 TI - [Treatment of cholestatic liver diseases; the role of ursodeoxycholic acid]. AB - Ursodeoxycholic acid (UDCA) allows symptomatic treatment of cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic biliary atresia, and cholestasis of cystic fibrosis. Patients should be treated at an early stage of the disease in order to prevent progression to cirrhosis. Since UDCA has no toxic effects longterm treatment with this substance is possible without the risk of undesired side effects. In patients with primary biliary cirrhosis and rapid progression of the disease, UDCA may be combined with an immunosuppressive substance (i.e. cyclosporin). In primary sclerosing cholangitis, biliary atresia and cholestasis of cystic fibrosis, UDCA at present seems the only treatment of which a benefit for the patients can be expected. In endstage disease liver transplantation is indicated. The role of UDCA in chronic hepatitis and alcohol induced liver disease needs to be clarified in further studies. Whether the improvement of laboratory tests in such patients indicates amelioration of the course of disease, still is unclear. PMID- 1441679 TI - [Percutaneous transhepatic cholangioscopic color laser lithotripsy in bile duct calculi]. AB - Tunable dye laser lithotripsy is an effective and low risk treatment in patients with bile duct stones in which transpapillary maneuvers failed. The percutaneous approach allows to introduce small caliber endoscopes (10.5 F) to fragment the calculi under vision. This technique was evaluated in 8 patients who had undergone a biliodigestive anastomosis or in whom the biliary calculi could not removed by standard retrograde treatment. Laser lithotripsy resulted in sufficient fragmentation in 7 patients. Bile duct clearance proved to be a particular problem with the percutaneous access. When a retrograde sphincterotomy is not possible an antegrade papillotomy must be attempted under fluoroscopic guidance. In bile duct strictures the implantation of expandable stents facilitates the passage of fragments and may prevent recurrent stricture and development of new stones. PMID- 1441680 TI - [Computerized tomography analysis of gallstones: soon an essential diagnosis before nonsurgical gallstone therapy?]. AB - Successful application of non operative procedures for gallstone therapy are limited on cholesterol stones. Therefore reliable therapeutic analysis of stone components is mandatory for planning of an adequate therapy. Computed tomographic gallstone analysis is considered to improve selection of patients significantly. However, standardized conditions for investigation of patients are not yet established. It is suggested that computerized tomography should be performed using 4 mm slides, standardized position of patients and a phantom, which allows calibration of different CT-machines. PMID- 1441681 TI - [Cytokine-assisted extrahepatic cellular binding of hepatitis B virus: pathogenic importance for cell tropism and virus replication?]. PMID- 1441682 TI - [Surgical measures in tropical chronic pancreatitis--are inflammatory complications, requiring surgical measures, less frequent in tropical chronic pancreatitis than in chronic alcoholic pancreatitis?]. PMID- 1441683 TI - [Use of ERCP in suspected bile duct and pancreatic cancer]. PMID- 1441684 TI - [Psychoimmunologic correlation between allergies, panic and agoraphobia]. AB - The present behavioral medical paper is a contribution to basic research in neuroimmunology. The relationship of panic/agoraphobia and allergy/anaphylaxis (IgE-mediated immediate reaction) is demonstrated and discussed with specific consideration of vasomotor reactions, tachycardia and hyperventilation in panic patients and allergies with anaphylactic reactions. The vegetative symptoms of panic reactions and anaphylaxis showed a high correlative correspondence. 74% of 23 panic and/or agoraphobia patients in a pretest to an epidemiologic study turned out to have an allergic illness that needed treatment; but there were no more anxiety disorders disclosed in 50 allergic patients than in the general population according to expectancies found in epidemiologic publications. If these data are confirmed then panic and agoraphobia cannot be seen as merely a cognitive-emotional event, but also as a further kind of allergic disease with genetic, ecological, psychological and social determinants; they would then have to be diagnosed as psychoimmunological disturbances and treated with behavior medicine (preferably with exposition and immunotherapy or hyposensitization). Anxiety therapies would improve qualitatively and could be cut down in duration. PMID- 1441685 TI - [A comparison of East German and West German probands: emotionality and objective personality variables]. AB - Data from a joint research project between the University of Trier and the Humboldt University Berlin of personality dimensions were compared and analyzed. Since Germany was separated for forty years, studies of the general population are necessary in order to yield possible cultural differences. In the present comparison we analyzed personality constructs like anxiety, curiosity, anger and anger expression as well as variables of objective personality tests. The sample from the former western German states contained N = 109 persons. As a basis for comparison, we selected a parallized matched sample (n = 109) from the new eastern German states out of a larger sample (N = 586). The main results were as follows: (1) reliability (consistency) and factor structure of the measures are similar for both samples. This equivalency is the formal prerequisite for a comparison. (2) There are substantial differential effects between eastern and western samples. Wellness as well as emotionality also show different results considerable with regard to age and sex. PMID- 1441686 TI - [Ethical aspects of psychotherapy]. AB - There are many ethical problems in theory and practice of psychotherapy. Aims of therapy, effectiveness, side effects and modalities of therapy are discussed in detail. The dependency of these aspects from anthropological considerations and understanding of illness is stressed. As far as side effects of psychotherapy are concerned abuse of the patient by the psychotherapist is distinguished from those potentially harmful effects which are due to the specific process of psychotherapy. The relationship of psychotherapy to psychopharmacotherapy is discussed in a special passage. PMID- 1441687 TI - [A multi-stage cognitive training program for improving cognitive functions of chronic alcoholic patients]. AB - In accordance with neuropsychological findings, that chronic alcohol abuse can lead to cognitive impairment, a multi-phased cognitive training program (MKT) developed by Sagstetter was conducted with a group of chronic alcoholic patients. In this article this program is introduced and evaluated with regard to chronic alcoholic patients and their improvement in certain cognitive functions. The study group consisted of 11 chronic alcoholics, who regularly took part in the program. The control group consisted of 11 patients who took part on a behavior therapy program offered by the clinic and had similar social and pathological histories to those of the study group. The two groups were compared with each other with the help of a follow-up study design after approximately seven weeks. The results reveal that this present cognitive training program promotes, above all, cognitive functions such as visual short-time memory, concentration, form perception as well as combination and organisation ability. PMID- 1441688 TI - [The hypochondriacal delusion]. AB - Hypochondriacal delusions are not bound to a specific mental disorder, but occur in the whole spectrum of psychoses. In spite of the implicitly wrong conception of reality, the significance of these delusions as an attempt to express, interpret and cope with mental illness should not be neglected if an approach to the patient's own experience is sought. On the one hand, hypochondriacal delusions are based on altered body perceptions in mental illness, characterized by primary local or general dysaesthesias to the point of depersonalisation, or caused secondarily by the patient's increased attention to his own body. This alienated bodily experience is named in (lay) medical terms by the delusional hypochondriac. On the other hand, "illness" with its manifold cultural and psychological meanings stands as a polyvalent metaphor for the incomprehensible alteration of the patient's self-experience in general: thus, the feeling of exposure to external attacks, of guilt, sinfulness, shame, loss of self-esteem or even the experience of a disruption of personality may find their expression in the hypochondriacal delusion. PMID- 1441689 TI - [German version of the Vanderbilt Psychotherapy Scales: description and use in two brief psychotherapies]. AB - The Vanderbilt-Psychotherapy-Scales appeared to be useful instruments for the identification of process characteristics determining the outcome of brief dynamic psychotherapies. The German versions of the two scales measuring important components of the psychotherapeutic process and of negative indicators are described in this article. It could be shown that--similar to the original versions--both scales can be used economically and that rater agreement soon reaches satisfactory levels. To demonstrate the potential use of the scales, their application in two different short term treatments are described which are presently analysed in a multi-center study of "single case oriented process research" using a variety of different methods. The example demonstrates that both scales are useful to discriminate both different theoretical foundations of the treatments as well as specific features of the patients and their therapists. The usefulness of the scales in a broader context is mainly based upon the experience that they reveal a lot of important informations about the psychotherapeutic process with a minimum of expense. PMID- 1441690 TI - [In situ detection of EGF receptor mRNA in arteriosclerotic lesions in man: implications for the proliferative activity of smooth muscle cells]. AB - Growth factors and growth factor receptors are considered to be key elements in the pathogenesis of arteriosclerosis and restenosis formation. To study the local expression of epidermal growth factor (EGF) receptor, plaque tissue specimens from advanced lesions (10 coronary, two femoral, seven carotid) of 19 patients were taken for in situ hybridization studies using an EGF-specific cDNA probe. In serial vascular sections of three lesions with increased focal cellularity, autoradiographic silver grains were clearly localized to intimal cells adjacent to the internal elastic lamina. EGF mRNA transcripts were not observed in the fibrous cap, the plaque shoulders, necrotic intimal areas, or in the media. In smooth muscle cells (SMCs) cultured from human plaque tissue, EGF increased SMC proliferative activity in a dose-dependent manner (ED50: 3-6 ng of EGF/ml). Proliferative responsiveness to EGF (10 ng/ml) was found to be significantly (p < 0.01) enhanced in coronary SMCs derived from restenotic lesions as compared to those from primary stenoses. The expression of EGF receptor mRNA in human atheromatous lesions could be of prognostic value to predict an increased SMC proliferative response to stimulatory growth factors. PMID- 1441691 TI - [The anti-ischemic effect of gallopamil-retard in comparison with nifedipine retard in stable angina pectoris]. AB - To assess the antiischemic efficacy of slow-release (SR) gallopamil, 100 mg b.i.d., versus slow-release (SR) nifedipine, 20 mg b.i.d., 24 patients with chronic stable angina underwent symptom-limited bicycle ergometer exercise stress tests in a randomized, placebo-controlled, double-blind, cross-over protocol. Both medications caused a significant reduction in anginal attack frequency and nitroglycerin consumption as compared to placebo; similarly, exercise tolerance was augmented in association with a considerable reduction in ischemia-induced ST segment depression. The antiischemic effect of gallopamil (SR) was marginally superior to that of nifedipine (SR). Since the incidence of adverse effects was also less with gallopamil (SR) this drug exhibited a more favorable risk-benefit ratio relative to nifedipine (SR). PMID- 1441692 TI - [Interval resistance exercise in comparison with bicycle ergometry stress. Studies with resistance endurance training in coronary patients]. AB - In the rehabilitation of coronary patients there is an increased interest in using complementary resistance exercise training. Therefore, we studied nine patients (males; age: 51 +/- 7 years) with chronic stable coronary heart disease during extensive resistance exercise (ex RE) (legpress, abduction, adduction) (60 s work: 60-s rest; contraction intensity: 65% of 1 RM) and during intensive resistance exercise (int. RE) (legpress) (30-s work: 45-s rest) with 85% of 1 RM. Non-invasive continuously measured blood pressure, heart rate, norepinephrine, epinephrine, lactic acid, and glucose were compared with values from maximal bicycle ergometry (3-min steps, each 25 w; max. performance: mean 156 w; range 125-200 w). RESULTS: 1) Comparing ex RE and int RE with bicycle ergometry there were no differences in blood pressure (systolic: 206 and 204 vs. 210 mm Hg; ns; diastolic: 98 and 104 vs. 92 mm Hg; ns). Heart rates (104 and 103 vs. 125/min; p < .01), norepinephrine (3.8 and 3.3 vs. 8.8 nmol/l; p < .01) and epinephrine (0.7 and 0.6 vs. 1.4 nmol/l; p < .01) were considerably lower. 2) The most significant increase and decrease of blood pressure and heart rate occurred within 15-30 s after the beginning and end, respectively, of isometric exercise. CONCLUSIONS: 1) ex RE is suitable for patients with stable CHD and cardiac exercise tolerances of 1.5-2 W/kg = 125-150 watts. 2) Blood pressure monitoring by the cuff method (RR) immediately after RE did not reflect blood pressure during RE. 3) Controlling RE by the training heart rate prescribed for endurance exercise is not possible. PMID- 1441693 TI - [Rotational stability of angiography catheters]. AB - Rotatory stability is a parameter that reflects the ability of a catheter to transmit a rotation applied at the outer end to the catheter tip for the purpose of selective probing. A method for measuring the rotatory stability is described, and the results of rotatory stability measurements of 70 different commercially available catheters are reported. There is an almost linear correlation between the rotatory stability and the difference between the respective fourth power of the external and internal diameter or, approximately, to the fourth power of the external diameter for catheters without wire reinforcement. With the same cross sectional dimensions, the rotatory stability of teflon, polyethylene, and nylon catheters has an approximate ratio of 1:2:4. Wire reinforcement increases rotatory stability by an average factor of about 3. For catheters of calibers 5 F and 6 F, a correlation between the rotatory stability and the weight of the reinforcing wire mesh is apparent. PMID- 1441694 TI - [Peripheral embolism of hemostasis collagen (VasoSeal)]. AB - VasoSeal is a purified bovine, absorbable collagen plug currently successfully used to close the femoral arterial puncture site after cardiac catheterization under full anticoagulation. Up to now there has been no experience with potential complications. We observed acute ischemia in the right lower leg of 2/100 patients 36 resp. 24 h after successful closure of the puncture site with VasoSeal. Angiography confirmed acute occlusion of the distal A. poplitea dextra. A 25-mm resp. 50-mm long cylindrical foreign body embolus was removed with a Fogarty-catheter by retrograde indirect embolectomy. Histopathology confirmed a fresh collagen clot with appositional thrombosis. PMID- 1441695 TI - [Pimobendan (UDCG 115 BS) in long-term therapy of chronic heart failure]. AB - Pimobendan is a positive inotropic agent with additional calcium-sensitizing effects of the phosphodiesterase III-inhibitor group. In short-term studies, beneficial hemodynamic effects have been demonstrated in patients with congestive heart failure. The aim of this prospective study was to examine the long-term effect of pimobendan (during at least 6 months) on subjective state, hemodynamic parameters, and arrhythmias in patients with congestive heart failure NYHA classes II and III. After double-blind randomization, 24 patients received pimobendan 5 mg bid or placebo orally in addition to a basic therapy (diuretics, digitalis). After 3 months, pimobendan-treated patients showed a significant clinical improvement (p < 0.03). In the placebo group, one patient underwent acute cardiac transplantation due to rapid clinical deterioration; another patient died suddenly after 5 months. No cardiac events occurred in the pimobendan group. In comparison to placebo, no proarrhythmogenic effect of pimobendan was detected. Clinical stabilization of patients in the pimobendan group was not paralleled by improvement of the hemodynamic parameters of left ventricular performance. PMID- 1441696 TI - [Function of the right ventricle in patients with dilated cardiomyopathy]. AB - To analyze right-ventricular size and function and their relationship to left ventricular dimensions in patients with dilated cardiomyopathy (DCM), biplane cineventriculography was performed in 57 patients. The results were compared to 15 normals (N). In patients dilatation of the right ventricle (RVEDVI: DCM: 126.5 +/- 41.4 ml/m2, N: 90.5 +/- 9.2 ml/m2, 2 p < 0.05) was less pronounced than dilatation of the left ventricle (LVEDVI: DCM: 136.0 +/- 45.8 ml/m2, N: 76.7 +/- 7.9 ml/m2, 2 p < 0.05). Left-ventricular ejection fraction (LVEF: DCM: 36.1 +/- 10.2%, N: 64.4 +/- 3.8%, 2 p < 0.05) was more reduced than right-ventricular ejection fraction (RVEF: DCM: 39.7 +/- 11.5%, N: 58.3 +/- 3.3%, 2 p < 0.05). Concerning the individual patient, a good correlation was found between right- and left-ventricular stroke volume (r = 0.74), whereas ejection fraction (r = 0.58), enddiastolic (r = 0.52) and endsystolic volume (r = 0.55) of the left and right ventricle correlated only moderately. Twenty-three of the 57 patients showed pronounced differences between right- and left-ventricular ejection fraction. The difference RVEF-LVEF was < = -10% in six patients, i.e., right ventricular ejection fraction was markedly more reduced than left-ventricular ejection fraction. Right-ventricular myocardial biopsy was performed in five of these six patients with histologic evidence of dilated cardiomyopathy and, also, no signs of right-ventricular dysplasia (no lipomatous tissue replacement).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441697 TI - [Initial presentation of ventricular pre-excitation after catheter ablation of concealed retrograde conducting accessory atrioventricular pathways]. AB - Catheter ablation using radiofrequency or direct current energy was performed in 19 consecutive patients with concealed accessory pathways. Four patients developed manifest preexcitation for the first time following ablation. The concealed accessory pathways of these four patients were localized at right lateral, left posteroseptal, left posterolateral, and left lateral sites, respectively. In two patients, manifest preexcitation developed immediately after attempted ablation. In the other two patients, preexcitation occurred after 4 and 14 days. Electrophysiologic testing revealed in all four patients that the origin of manifest preexcitation corresponded to the site of the concealed pathway. Successful catheter ablation using radiofrequency current was performed in three patients. One patient preferred surgical interruption of the accessory pathway. The reason for this sudden emergence of preexcitation of these patients with only retrograde conducting pathways remains to be investigated. The anterograde conduction capacity might have been modified by damaging the site of the accessory pathway insertion. PMID- 1441698 TI - [Successful treatment of atrial fibrillation by resection of a congenital aneurysm of the left heart atrium]. AB - Atrial fibrillation occurred in a 27-year-old patient with a history of globular cardiac enlargement since childhood. Because of the probable causal relationship between the preexisting heart disease-which was supposed to be an enlargement of the left atrium-and the rhythm disturbance, we recommended a surgical intervention. Cardiac surgery revealed a congenital aneurysm of the left atrial appendage which could be resected without any complication. Postoperatively, atrial fibrillation had returned to regular sinus rhythm. The bad prognosis with a high risk of systemic embolism is the reason why early cardiac surgery should be performed after diagnosis of this rare anomaly (20 reported cases) of the left atrium. PMID- 1441699 TI - [Cardiovascular intensive care. Report of the meeting of the "Cardiovascular Intensive Care" Study Group at the spring congress of the German Society of Cardiovascular Research 23 April 1992 in Mannheim]. PMID- 1441700 TI - [Effectiveness of propafenone in congenital ectopic junctional tachycardia--a case report]. AB - Junctional ectopic tachycardia is associated with a poor prognosis when it occurs in newborns and young infants. Like other automatic tachyarrhythmias, junctional ectopic tachycardia has been shown to be very resistant to medical treatment. Successful therapy with propafenone in a newborn with congenital junctional ectopic tachycardia is presented. Due to its high effectiveness, safety, and lack of side-effects, propafenone appears to be a valuable drug in the treatment of young patients with congenital junctional ectopic tachycardia. PMID- 1441701 TI - [Percutaneous high frequency current catheter ablation in permanent ventricular tachycardia of the "bundle-branch reentry" type after implantation of an automatic cardioverter-defibrillator]. AB - A 65-year-old female patient with a history of recurrent sustained ventricular tachycardia presented with an incessant ventricular tachycardia (cycle length 360 400 ms) following implantation of a cardioverter-defibrillator (ICD). The tachycardia could not be terminated by antiarrhythmic drug treatment, antitachycardia pacing or internal defibrillation via the ICD. An invasive electrophysiologic study revealed that the mechanism of this newly occurring tachycardia was bundle branch reentry. The patient underwent emergency catheter ablation using radiofrequency (RF) current. Endocardial mapping of the right bundle branch and of the distal His bundle was performed and a bundle branch reentry tachycardia was diagnosed. After delivery of the fifth RF-impulse, the tachycardia terminated and complete AV block was induced. No malfunction of the ICD was observed following RF-ablation. The patient was hemodynamically stable with a junctional escape rhythm and antibradycardia pacing back-up of the ICD (VVI-mode). This case report demonstrates the feasibility of RF catheter ablation in the treatment of incessant bundle branch reentry tachycardia as a complementary option after implantation of an ICD. PMID- 1441702 TI - [Unexpected malposition of a ventricular pacemaker electrode]. AB - Ten years after mitral-valve replacement, a 69-year-old patient underwent VVI pacemaker implantation because of symptomatic bradyarrhythmia. Postoperatively, the electrocardiogram showed a right bundle branch pattern under ventricular stimulation while the threshold was optimal. Under fluoroscopy, we suspected a malposition of the electrode outside the right ventricle in the LAO and lateral view. This could not be verified by echocardiography, whereas contrast angiography of the right ventricle proved the extracavitary position of the electrode under the inferior wall of the left ventricle, probably in the middle cardiac vein. The electrode position was operatively corrected without complications. We discuss different ways of malposition and their detection by considering electrocardiographic configuration and fluoroscopy in LAO and lateral view. PMID- 1441703 TI - [Pulmonary valve atresia with ventricular septum defect: interventional recanalization of the right ventricular outflow tract]. AB - A case of pulmonary atresia with ventricular septal defect is reported where continuity between the right ventricle and the hypoplastic pulmonary artery was established interventionally. The atretic valve was perforated using a special "perforation needle" with a sharp and stiff distal and a flexible proximal part. Perforation of the bifurcation was well tolerated without later sequelae. After perforation of the atresia, dilation was successfully performed using 2, 4, and 7.2 mm balloons with a pressure of 10 atm; the arterial oxygen saturation increased from 72% to 84%. Four weeks later repeated "valvuloplasty" was performed (balloon diameters 8 mm, 9.5 mm, and 12 mm) and the "valve" ring was dilated to a diameter of 10.5 mm. Although no general conclusions can be drawn from this single application, mechanical perforation of the atresia could become an attractive interventional approach for the treatment of pulmonary atresia. PMID- 1441704 TI - [Acute and intermediate clinical and angiography results after coronary stent implantation]. AB - The value of stenting in emergency situations in interventional angioplasty procedures is widely accepted. Stenting remains controversial as a therapeutic method for use beyond the acute phase, as the results reported in the acute phase are characterized by a wide range. This study reports the implantation results of Palmaz-Schatz stents in 64 cases mostly for failed PTCA. Stents were mounted on Monorail-PVC-balloon catheters. The acute success rate was 96.8%. In two cases with stent misplacement CABG was performed within 48 h. No lethal events occurred in the acute phase. Stent thrombosis has only been seen in four cases (6.5%) so far under subtle monitoring of the anticoagulant regime. Restenosis rate (definition: NHLBI-4) according to serial angiography 6 and 12 weeks after implantation was 4.25% at 6 weeks, with a cumulative rate of 19.4% up to 12 weeks. All recurrences eligible for PTCA have been successfully redilated. A high extracardiac complication rate--predominantly groin hematoma--is the main disadvantage of the procedure. Surgical repair was necessary in 11.4% up to 6 weeks after implantation. Surprisingly high was also the incidence of hematuria, also in 11.4%, in the phase of high anticoagulation. In conclusion, stenting is an effective therapeutic method to avoid emergency CABG and elective CABG in most cases of failed PTCA. PMID- 1441705 TI - [Randomized comparison between collagen administration and pressure dressings for occlusion of the arterial puncture after coronary angiography and coronary dilatation]. AB - One hundred patients undergoing routine diagnostic or interventional catheterization were randomly assigned to receive either percutaneously applied collagen (group A; n = 50) or conventional pressure dressing (group B; n = 50) for sealing of the femoral artery. Clinical variables were comparable in both groups. The heparin dose was 100 IU/kg in 30 patients and 200 IU/kg in 20 patients of both groups. The average compression time was 4.3 min in group A and 42.3 min in group B (p < 0.001). In group A, 1/50 patients required pressure dressing compared to 50/50 patients in group B. Bleeding was not observed in group A, but was observed in 6/50 patients in group B. The time to ambulation was 6.4 (range, 4-12) h in group A and 21.6 (range, 10-48) h in group B (p < 0.001). Hematomas with a diameter of > 6 cm developed in 4/50 patients in group A and in 11/50 patients in group B (p < 0.05). Blood-transfusions or surgical interventions were not required and there was no loss of ankle pulses in either group. In conclusion, percutaneously applied collagen reduced compression time and duration of bedrest after diagnostic catheterization and PTCA. Despite earlier ambulation, the incidence of bleeding was lower with collagen than with conventional pressure dressing. PMID- 1441706 TI - [Spontaneous renal artery dissection]. AB - The clinical clues of sudden arterial hypertension, acute pain in the side, proteinuria, hematuria, abdominal bruits and renal failure are suspicious for spontaneous dissection of the renal arteries, even in the absence of one or more of the above-mentioned symptoms. To confirm the diagnosis and to provide appropriate therapy, immediate renal arteriography is mandatory, otherwise acute loss of renal tissue may occur. We report on one patient with spontaneous dissection of the renal arteries. PMID- 1441707 TI - [Geriatric diseases of the upper digestive tract]. AB - During aging, secretion and motility of the upper GI tract slow down. The reduction of these functions, however, does not create complaints. In the higher age groups, a number of symptoms from age-dependent diseases occur more frequently, e.g., dysphagia in response to cerebral ischemia, or disturbed gastric emptying caused by diabetic visceral neuropathy. Moreover, certain GI diseases occur more often in the elderly, e.g., chronic atrophic gastritis, NSAR induced gastric ulcers, malignancies, and others. In contrast, almost nothing is known about diseases or symptoms of the GI tract that might be specific for the elderly. With only a few exceptions, there are no age-dependent clinical differences. Nevertheless, intestinal diseases often develop more rapidly and the mortality is higher in the elderly than in younger people. PMID- 1441708 TI - [The small and large intestine. Fecal incontinence]. AB - Except for impaired resorption of vitamin D and calcium, the small bowel does not exhibit significant functional impairment during aging. Vascular problems in the small and large bowel are rare, but are of dramatic importance. Chronic constipation and diverticulosis are classical disorders of aging which should be treated by adding fiber to the normal diet. Surgery is only indicated in the case of complicated diverticulitis. Adenoma and colorectal carcinoma show an age related incidence. Angiodysplasia, preferentially localized in the caecum, is the major cause of lower gastrointestinal tract hemorrhage. Anal incontinence may be multifactorial, behavior modification and biofeedback may help to avoid surgery. PMID- 1441709 TI - [Gastrointestinal motility in the elderly]. AB - The existence of specific, age-related changes in gastrointestinal motility with clinical significance is controversial. Beside the more infrequent primary motility disorders, secondary motility disturbances associated with collagen vascular diseases, endocrinopathies, and neuromuscular diseases are prominent in the older and often multimorbid patients. Especially in geriatric patients, motility associated symptoms are undesired side-effects of drug therapy. The pathophysiology, clinical syndromes, and therapeutic principles of motility disorders in the elderly are discussed. The major symptoms of esophageal dysfunction are dysphagia, chest pain, heartburn, and regurgitation. Oropharyngeal dysphagia, mostly caused by cerebrovascular accidents and other neurologic disorders, leads to disturbances in food intake, and is often complicated by broncho-pulmonary infections arising from recurrent aspiration of food or saliva. Gastrointestinal reflux disease and spastic motility disorders of the esophagus are regarded as possible causes of angina-like chest pain after exclusion of cardiac diseases. Motility disturbances of the stomach and small bowel are often related to systemic disease (i.e., diabetes mellitus, chronic intestinal pseudo-obstruction) of drug side-effects. Mental and physical decline, reduced fluid intake, and constipating drugs are the most relevant factors for idiopathic constipation in the elderly. Fecal incontinence means a great psychological strain for older patients and leads to social isolation. PMID- 1441710 TI - [The significance of current hepatitis virology for geriatrics]. AB - In geriatric medicine, hepatitis A is of minor interest only because protecting antibodies have been demonstrated in 92% of the elderly. Hepatitis B (which, prior to recognition of major routes of transmission, was predominantly transmitted percutaneously) has gained importance only by its chronic residuals in aged patients; acute infection in the elderly is rare. The recently detectable posttransfusional hepatitis C is the most important type of viral hepatitis in the elderly. In our region, hepatitis D is rare and hepatitis E has not yet been observed. PMID- 1441711 TI - [Calculi of the bile ducts--a problem for the elderly? Observations from the surgical viewpoint]. AB - Age alone does not increase the risk in biliary surgery. However, cholelithiasis in the elderly is often associated with an increased frequency of acute cholecystitis and cholangitis due to stone obstruction. The proportion of elderly people in the world is still growing, therefore, we can expect to see increasingly more complications of gallstones. Elective surgery for gallstone disease in all age groups is to be preferred to a policy of waiting for stone complications with the resultant risk of higher mortality and postoperative morbidity of emergency surgery. PMID- 1441712 TI - [Housing for the elderly--results of an empirical study]. AB - This empirical study is based on 285 standardized interviews with older people living in government-subsidized housing (sozialer Wohnungsbau). Housing conditions, especially contentment and perceived deficiencies are described. Additional remarks refer to the neighborhood relations. The high contentment, already known from former studies, is confirmed by the results. The findings indicate that steps towards an adaptation of housing conditions to possible needs of older people are not ranked very high. Beyond that, there seems to be a lack of information about the technical possibilities of improving the housing conditions, although older people want to live as long as possible in their current housing. PMID- 1441713 TI - Changes in thyroid hormones and serum lipids of aged women following thyroidectomy. AB - Thyrotropin (TSH), thyroxine (T24) 3,5,3403 triiodothyronine (T23), serum lipid levels and ECG findings in females who underwent thyroidectomy 2-44 years earlier, were compared to those of similar controls with intact thyroid. Pathological ECG is more frequent in thyroidectomized persons who also exhibit higher thyrotropin and lower HDL-cholesterol levels. The results indicate that thyroidectomized state should be regarded and controlled as a possible condition of subclinical hypothyreosis, being a risk factor of cardiovascular diseases. PMID- 1441715 TI - Influence of age and sex on 19 blood variables in healthy subjects. AB - Normal values exist for all clinical chemical tests, but it is not very clear what is normal for healthy elderly subjects. Therefore, routine blood variables were determined in 80 ambulatory, disease-free persons who had undergone rigorous health screening. The subjects were divided into the following age groups: 20 (+/ 3), 40 (+/- 3), 60 (+/- 3), and 80 (+/- 5) years, with 10 males and 10 females per age group. Blood variables were determined after an overnight fast. It was found that even with conservative statistical measures more than half of the variables were significantly affected by age or sex. Significant age differences were found for total cholesterol, triglycerides, sodium, and ASAT. Urea, creatinine, gamma-GT, phosphate, alkaline phosphatase, and albumin were characterized by both age and sex differences. No age or sex differences were found for glucose, potassium, chloride, calcium, calcium ion, iron, magnesium, total protein, and ALAT. The findings suggest that the age or sex-related changes of a number of blood variables such as cholesterol, triglycerides, and liver enzymes are not only of statistical significance, but are also of clinical relevance. PMID- 1441714 TI - [Thyroid gland disorders in elderly psychiatric patients]. AB - With 200 admissions of 192 patients to the psychogeriatric acute ward of the Zwiefalten State Mental Hospital serial measurements of serum concentrations of basal TSH and, if necessary, of total T3 and total T4 were carried out with the TRH tests performed. Basal TSH was decreased in 16% of patients and in 2% it was increased. Only three patients had manifest hyperthyroidism and one patient had marginal hypothyroidism. Regardless of their psychiatric diagnosis, patients with manifest hyperthyroidism showed psychomotor agitation, whereas those with latent and marginal hypothyroidism suffered from lack of impulse. These symptoms improved after treatment with carbimazol or levothyroxine, respectively, and psychotropic drugs. Therefore a thyroid screening should be performed on psychogeriatric patients regardless, including, when possible, repeat measurement of basal TSH and, if necessary, the test battery should include total T3 and total T4. PMID- 1441716 TI - Cortical bone age estimates from historically known adults. AB - Adult skeletal remains from 19th century historic cemeteries were used to test the accuracy and precision of age estimations based on the cortical bone histological technique proposed by Thompson [6, 7]. Comparison of estimates made from anterior microscopic fields versus peripheral fields (N = 29 femora) indicates general age agreement, with 6/29 demonstrating marked differences between sampling locations. Three cases of unilateral trauma show no consistent effect on bone age estimates. Among sixteen adults of known age, the ages of eight were accurately estimated; five were estimated to be significantly older and three were estimated to be younger than they were. It is argued that cortical erosion/diagenetic destruction may contribute to overestimation by obscuring the periosteal regions required for application of the technique. While not without its shortcomings, it is concluded that the Thompson technique is relatively robust and merits further development. PMID- 1441717 TI - Incisification of anthropoid deciduous mandibular canines. AB - Interspecific variation of the deciduous mandibular canine's mesial cristid in 51 anthropoid taxa is assessed. In 84% of the taxa observed, mesial cristids were well developed and provided incisor-like occlusion with di2. In 5 of the remaining 8 taxa, lingual cristids provided incisor-like occlusion with dc1. Comparisons between dc1s and C1s of conspecific adult males and females show that in 85% of the species observed the magnitude of mandibular canine incisor traits follows this order: deciduous > adult female > adult male. This within-species variation is inversely related to the likely adaptive value of the canine as a weapon and to canine crown height. A selection model based on these data is derived and applied to human canine evolution. The relevance of these data to the field vs. clone theory debate about dental development is also discussed. PMID- 1441718 TI - Estimation of stature in children from second metacarpal measurements. AB - On the basis of 552 boys and 542 girls aged 6 to 20 years, this study examines the estimation of stature from dimensions and maturity of second metacarpals by means of linear regression equations. A combination of length and width measurements provided a more accurate estimation than each measurement individually. When taken alone, length produced a more accurate estimation than width. Sex and age factors are useful for the estimation of stature, though these variables are often unknown in the isolated bone. The samples are divided into immature and mature groups (according to skeletal maturity). Regardless of sex, stature could be estimated from the metacarpal length and width with a standard error of 4.19 cm by means of a multiple linear equation in the immature group. The mature group should be considered with adults for this purpose. Thus, taking into account their skeletal maturity, living stature could be practically estimated from the second metacarpal with significant degrees of accuracy in children. PMID- 1441719 TI - "Lucy's" body height and relative leg length: human- or ape-like? AB - The body height of Australopithecus afarensis A.L. 288-1 ("Lucy") has recently been estimated and calculated as between 1 m to 1.06 m; other estimates give ca. 1.20 m. In addition, it is often stated that her relative leg length was shorter than that of modern humans. Using relative leg-, femur- and tibia length it is shown that both statements together can not be true; either her body height must at least have been around 1.06 to 1.10 m to give "Lucy" human-like leg proportions, or, to achieve a shorter, more ape-like leg ratio, a body height of ca. 1.20 m must be assumed. PMID- 1441720 TI - Secular trend of menarcheal age in southern Chinese girls. AB - Southern Chinese girls aged 11 years and 9 months to 12 years and 3 months in Hong Kong have a mean menarcheal age of 11.50 years (standard deviation of 0.47) using the recollection method. Highly significant differences are found when compared to the 12-year-old girls in Hong Kong studied in the past decades. Therefore, a secular trend of earlier menarcheal age is demonstrated. PMID- 1441721 TI - Emergence of deciduous teeth in Punjabi children, north India. AB - Data on deciduous tooth emergence of 312 children aged 4 to 31 months of Punjabi parentage are presented. Probit analysis was used to derive the median age of tooth emergence. Female children are found to be advanced with respect to tooth emergence than their male counterparts. While comparing the present data with those from other populations it is found that, in general, the mean number of emerged teeth in Punjabi children is more at most ages, with lower median age of eruption for most teeth. Magnitude of interage variability in the eruption times is noticed to be maximum in the 16-17 and 20-21 months age groups. The findings of the study suggest that number of teeth can be used as a parameter for the estimation of age. PMID- 1441722 TI - Asymmetry and sexual dimorphism of lungs weight in fetal ontogeny. AB - 1079 male fetuses and 727 female fetuses at the age of 20 to 41 weeks were investigated for the process of asymmetry and sexual dimorphism of lungs weight formation as well as developmental correlation between the weight of the lungs and the size of the heart. Statistical analysis of the results was applied. It was ascertained, among others, that asymmetry of lungs weight occurs in the investigated developmental period--the right lung is heavier than the left one about 20 to 30%. Between the increase in the weight of the lungs and the size of the heart positive correlation occurs, but it is not of directed character. A substantial, intersexual differentiation of lungs weight was not ascertained. PMID- 1441723 TI - Origin of the Romany gypsies--genetic evidence. AB - Genetic heterogeneity and affinity was examined between nine Romany speaking gypsy populations and two of their possible ancestral populations from India. For AB0, Rhesus (D), MN and HP systems there exists a conclusive heterogeneity among these populations. Three gypsy populations from Western Europe (English, Welsh and Swedish) are genetically distinct from the rest of the East European gypsies and the populations of India analysed in this investigation. Overall the genetic differentiation among these populations is moderately high (RST = 0.029). The results also indicate the relative close relationship among the East gypsies and the two selected nomadic populations of India. The factors responsible for the moderate diversification of the East European gypsies may be high rate of migration, isolation and random drift, while among the Western gypsy populations admixture seems to be an important differentiation factor. PMID- 1441724 TI - Flatness of facial skeletons in Siberian and other circum-Pacific populations. AB - Thirty-four populations from Siberian and other circum-Pacific regions were compared in terms of facial flatness measurements of the cranium. While fundamentally having an extremely flat face, Siberian populations tend to be differentiated into two or three subgroups. On the other hand, other Mongoloid populations show greater variation in facial flatness. The less flat faces of the American Indians are almost equal to those of the Europeans. In Japan, the existence of two contrasting groups in terms of facial flatness have been found. PMID- 1441725 TI - Investigations on the variability of blood group polymorphisms among sixteen tribal populations from Orissa, Madhya Pradesh and Maharashtra, India. AB - Sixteen tribal populations from Orissa, Madhya Pradesh and Maharashtra have been typed for the polymorphic blood group systems A1A2B0, MNSs, Rhesus, Kell, Duffy and Diego. The heterogeneity in the distribution of haplotype and allele frequencies, respectively, is partly considerable. It is supposed that this is due to the operation of several microevolutionary factors, such as genetic drift, social and geographic isolation and gene flow. This is discussed in detail. PMID- 1441726 TI - Apes and apomorphies: the anterior nasal spine as a projection of cladistic conceptions. AB - Projections, tubercles, or spines of bone at the anterior margin of the piriform aperture occur in widely varying forms among catarrhine primates. This paper describes, illustrates, and tabulates the frequencies of such structures by age and sex in a large collection of Pan troglodytes verus skulls. In the overall sample of 263 skulls where the region could be observed, these protuberances of bone occur bilaterally in 10.7% of specimens and unilaterally in an additional 3.4%. They increase in frequency with age to a high of 16.9% in adult and older animals. Among adult specimens, these projections of bone in the anterior nasal region are present more commonly in females than in males. In a comparative context, variants on this structure in nonhuman primates, some of them documented previously, should help to counter the cladistic conception that the anterior nasal spine is an apomorphic or evolutionary novel morphological structure in hominids. PMID- 1441727 TI - Experimental evaluation of antitoxic protective effect of new cholera vaccines in mice. AB - Intraperitoneal immunization of mice and subsequent challenge with purified cholera toxin (CT) were employed to evaluate the anti-cholera toxin protective effect of two new oral cholera vaccines, live CVD 103-HgR and killed B subunit whole cell (BS-WC). CVD 103-HgR vaccine demonstrated 100% protection of mice against 2.25 LD50 and 70% against 3 LD50 of CT. Mice immunized with BS-WC vaccine were protected against 2.25 and 3 LD50 of CT in 88 and 62% of cases, respectively. All three killed parenteral vaccines failed to protect against CT. We suggest this mouse system for preliminary evaluation of the antitoxic protective activity of cholera vaccines. PMID- 1441728 TI - A single vaccination with an inactivated hepatitis A liposome vaccine induces protective antibodies after only two weeks. AB - In the near future an inactivated hepatitis A vaccine will be commercially available. The recommended vaccination schedule will include at least two vaccinations 1 month apart. Giving two doses of vaccine on the same day in one injection results in protection after 2-4 weeks dependent on the adjuvant used. Hepatitis A virus incorporated into liposomes proved to be a suitable formulation in term of rapid seroconversion, high level of mean antibody content and low reactogenicity. PMID- 1441729 TI - Compulsory and non-compulsory immunizations: contraindications perceived by medical practitioners. AB - A total of 284 general practitioners (GPs), paediatricians and doctors of public vaccination centres (DPVC) were interviewed to investigate their willingness to immunize children with compulsory (diphtheria-tetanus, oral polio) and non compulsory (measles, pertussis) vaccines in the presence of 19 different medical histories. We observed a reluctance to immunize in the case of false contraindications, a lack of information mainly about non-compulsory immunizations, and doubts about the real contraindications to polio, measles and pertussis vaccines. The frequency of correct answers to the question posed was significantly higher in the group with less than 20 years of experience, and the DPVCs proved better informed about immunization. However, the crucial role played by the GPs and paediatricians' advice can prejudice the correct use of active immunization. PMID- 1441730 TI - Liposomes enhance the immunogenicity of reconstituted influenza virus A/PR/8 envelopes and the formation of protective antibody by influenza virus A/Sichuan/87 (H3N2) surface antigen. AB - Reconstituted influenza virus (A/PR/8 strain) envelopes (RIVE) and influenza virus (A/Sichuan/87 (H3N2) strain) surface antigens were entrapped in dehydration rehydration vesicles (DRV liposomes) composed of egg phosphatidylcholine (PC) or distearoyl phosphatidylcholine (DSPC DRV) and equimolar (32 mumol) cholesterol. Entrapment values for RIVE were 31.2 (PC) and 29.4% (DSPC DRV) of the material used. Corresponding entrapment values for the A/Sichuan/87 strain antigens were 40.7 and 39.3%. Balb/c mice injected intramuscularly with PC or DSPC DRV liposomes containing 0.1 and 1.0 microgram RIVE exhibited primary (higher dose only) and secondary responses (IgG1) which were significantly higher than those obtained in mice injected with identical amounts of non-entrapped RIVE. Significantly higher secondary responses were also observed for the IgG2a and IgG2b subclasses. In experiments designed to assess the effectiveness of DRV liposomes as a carrier of influenza virus antigens in a potential vaccine, hamsters were immunized intramuscularly with 0.1, 0.5 and 5.0 micrograms of free or liposome-entrapped influenza A/Sichuan/87 surface antigens. Results showed increased haemagglutination inhibition (HI) antibody levels in terms of both primary (0.5 and 5.0 micrograms doses) and secondary (all doses) responses in the sera of animals treated with the liposomal formulations. DSPC compared with PC DRV exhibited greater adjuvanticity when the lower doses of antigens were used. PMID- 1441731 TI - Inhibition of immune responses against rabies virus by monoclonal antibodies directed against rabies virus antigens. AB - Treatment of mice with a cocktail of murine anti-rabies monoclonal antibodies (mAb-C) interfered with the ability of these animals to mount a virus neutralizing antibody response to rabies vaccine. Administered mAb-C did not affect the induction of rabies virus-specific T-helper cells. The magnitude of the inhibition of rabies virus-specific B-cell response was dependent on the concentration of the mAb-C and the duration of the mAb-mediated interference was inversely proportional to the biological half-life of the mAb. As long as the serum titres were above a critical threshold, the suppression could not be overcome even by multiple vaccinations. Since injection of mice with immunocomplexes consisting of inactivated rabies virus and mAb rendered the animals non-responsive to a subsequent vaccination with inactivated rabies virus, it is concluded that the mAb-induced suppression might be caused by the formation of antigen-antibody complexes which exert a negative signalling effect to premature B cells. PMID- 1441732 TI - Genotypic and phenotypic characterization of an aroD deletion-attenuated Escherichia coli K12-Shigella flexneri hybrid vaccine expressing S. flexneri 2a somatic antigen. AB - The construction and characterization of EcSf2a-2, an aroD-deleted Escherichia coli-Shigella hybrid vaccine carrying chromosomal and plasmid genes from Shigella flexneri and expressing S. flexneri 2a somatic antigen in association with E. coli K12 core are described. Expression of hybrid lipopolysaccharide and deletion of aroD resulted in the attenuation of phenotypic characteristics associated with pathogenicity. The addition of an aroD deletion results in a requirement for an aromatic precursor of para-aminobenzoic acid (PABA), an essential bacterial metabolite not present in mammalian tissues. The biosynthesis of hybrid somatic antigen prevents expression of a Sereny-positive reaction by invasive bacteria capable of expressing a plaque-positive phenotype. A functional kcpA gene is required for expression of the plaque-positive phenotype. The presence of an aroD deletion does not interfere with expression of an invasive phenotype; however, in bacteria containing a functional kcpA gene, replication and spread by invading bacteria are limited, preventing development of the plaque-positive phenotype. PMID- 1441733 TI - B30-MDP, a synthetic muramyl dipeptide derivative for tumour vaccination to enhance antitumour immunity and antimetastatic effect in mice. AB - The effect of a muramyl dipeptide derivative (B30-MDP) on the augmentation of antitumour immunity against highly metastatic L5178Y-ML25 mouse lymphoma cells was examined in CDF1 (Balb/c x DBA/2) mice. Mice immunized with a mixture of X irradiated tumour cells (10(3)) and B30-MDP (100 micrograms) on 7 days prior to challenge by viable tumour cells displayed a significant decrease in metastasis towards the target organs, liver and spleen, compared with that of untreated mice. Immunization of mice with the mixture on day 5 or 7 after tumour challenge, when the level of glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in sera of mice inoculated with viable tumour cells was observed to be normal, caused less metastasis than immunization with X-irradiated tumour cells alone. Sensitization with X-irradiated tumour cells admixed with B30 MDP induced almost two times higher cytotoxicity of spleen cells against L5178Y ML25 lymphoma cells than sensitization with X-irradiated tumour cells without B30 MDP. In contrast, cytotoxic activity of spleen cells against another target, L1210 lymphoma cells derived from BDF1 mice, was not observed by immunization with X-irradiated L5178Y-ML25 cells with or without B30-MDP. Specific lysis by splenic cells of the immunized mice against L5178Y-ML25 cells decreased to the normal level when T cells were deleted from the immunized spleen cells by the treatment of rabbit anti-mouse Thy1.2 antibody and rabbit complement. These results indicate that B30-MDP is able to augment a specific tumour immunity due to the enhancement of cytotoxicity mediated by T lymphocytes, and is useful as an immunopotentiating agent for active immunization of inactivated tumour cells. PMID- 1441734 TI - Immune response to hepatitis B vaccine in parenteral drug abusers. AB - Responsiveness was assessed to a programme of vaccination of hepatitis B vaccine in a cohort of 197 intravenous drug addicts (mean age, 23.7 years) and their antibody response was compared with that of 271 healthy controls (mean age, 24.2 years). All participants were seronegative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). The vaccination schedule consisted of three intramuscular injections (deltoid area) at months 0, 1 and 2. Although 70% of parenteral drug abusers received the three doses of vaccination, only 43.6% were evaluable for immune response. Fifty-eight per cent of heroin addicts and 80% of controls had evidence of anti-HBs seroconversion at 1 month after vaccination (chi 2 = 15.52, p less than 0.001). Geometric mean antibody titres were also significantly higher in controls (69.1 IU l-1; confidence interval 95%, 56.83 and 84.04) than in parenteral drug abusers (18.2 IU l-1; confidence interval 95%, 12.85 and 25.73) (F = 20.951, p less than 0.0001). The anti-HBs response was not influenced by coexistent anti-HBc, HCV antibody or HIV antibody seropositivity. PMID- 1441735 TI - Effects of sample processing on the measurement of specific intestinal IgA immune responses. AB - The effects of techniques commonly used in the collection and processing of human intestinal fluid on the specific secretory immunoglobulin A (sIgA) response following oral immunization with the live typhoid vaccine Salmonella typhi Ty21a were examined. It was observed that the failure to adjust specific intestinal anti-typhoid lipopolysaccharide IgA antibody titres for total secretory IgA resulted in a false-negative detection rate of 19.8% and a false-positive detection rate of 7.4%. Furthermore, these specific responses were significantly diminished if the intestinal fluid was subjected to heat inactivation to reduce intestinal protease activity (p = 0.0083), but were not affected if stored at -70 degrees C for up to 1 year, without heat inactivation. It was concluded that in the processing of the intestinal fluid samples for specific sIgA determination heat inactivation significantly reduced specific sIgA titres, and that the failure to adjust absolute titres for total sIgA content resulted in a significant false-negative detection rate. PMID- 1441736 TI - In vitro translation of a subgenomic mRNA from purified virions of the Spanish field isolate AST/89 of rabbit hemorrhagic disease virus (RHDV). AB - Purified preparations of the Spanish field isolate of rabbit hemorrhagic disease virus AST/89 were found to contain the plus-stranded genomic RNA of more than 7.4 kilobases (kb) and large amounts of a subgenomic mRNA of 2.4 kb. The smaller RNA was translated in vitro and shown to code for a 60 kDa protein which was immunoprecipitated using anti-RHDV as well as anti-VP60 sera. PMID- 1441737 TI - A carboxy-terminal mutant spleen focus-forming virus (SFFV) envelope glycoprotein is transport-competent, but non-leukemogenic. AB - The Friend spleen focus-forming virus (F-SFFV) codes for a transport-defective leukemogenic envelope glycoprotein designated as gp52. We have previously shown that the external domain of gp52 carries the determinants responsible for its transport defect. Consistent with this idea, truncated gp52 molecules that lack a hydrophobic membrane anchor were transport-defective, and were not secreted from cells. In this report, we describe the construction of a mutant SFFV envelope gene that codes for altered gp52 molecules in which the carboxyl-terminal hydrophobic residues are replaced with exogenous hydrophilic residues encoded by the vector-derived sequences. The mutant env gene was expressed using the retroviral expression vector, pLXSN, and the mutant envelope protein was found to be transport-competent, and efficiently secreted from the cells. However, M-MuLV pseudotypes of the retroviral vectors expressing the mutant genome were found to be non-leukemogenic in mice. PMID- 1441738 TI - Alterations in the levels of expression of specific cellular genes in adenovirus infected and -transformed cells. AB - There is increasing evidence that changes in the transcriptional program of cellular genes in virus-transformed cells can contribute to virus transformation. It is, therefore, important to study altered expression patterns of cellular genes in adenovirus-infected and -transformed cells. We have used 40 different cellular genes or gene segments as hybridization probes to analyze the cytoplasmic RNA from adenovirus type 2 (Ad2)-infected KB cells, from Ad5 transformed human cells (293) or from several Ad2- or adenovirus type 12 (Ad12) transformed hamster cell lines. Many of the genes probed were not expressed in human or hamster cells. Transcription of the ADPRT and the heat shock protein 70 genes was increased in Ad2-infected KB cells and in 293 cells. In Ad2-infected KB cells, c-myc gene transcription was decreased. In 293 cells and in three adenovirus-transformed hamster cell lines (T637, BHK21-Ad2E1A-E1B, and BHK21-Ad2 HindIII-G), the transcription of the c-jun gene was increased, whereas c-myc transcription was decreased in the latter two cell lines. The data presented here demonstrate that, among 40 different mammalian gene probes, alterations in steady state levels of RNA were detected for five of these genes. These results suggest major alterations in transcription patterns in adenovirus-infected and transformed cells. PMID- 1441739 TI - Mercaptoethanol and dithiothreitol decrease the difference of electrochemical proton potentials across the yeast plasma and vacuolar membranes and activate their H(+)-ATPases. AB - Mercaptoethanol and dithiothreitol (DTT) inhibited the acidification of external medium by Saccharomyces carlsbergensis cells and protoplasts during glucose oxidation. The inhibition was also observed when cells were incubated with mercaptoethanol or when mercaptoethanol and DTT were used to prepare protoplasts. Experiments with S. carlsbergensis plasma membrane vesicles and vacuoles showed these thiol reagents to inhibit ATP-dependent generation of delta pH and Em across plasma membrane vesicles and vacuoles but to activate their H(+)-ATPases. Mercaptoethanol and DTT are suggested to de-energize plasmalemma as well as tonoplast by increasing their H(+)-permeability and to disturb the cell ion homeostasis. PMID- 1441740 TI - Genetic homology between Saccharomyces cerevisiae and its sibling species S. paradoxus and S. bayanus: electrophoretic karyotypes. AB - Chromosomal DNAs of many monosporic strains of the biological species Saccharomyces cerevisiae, S. paradoxus and S. bayanus were analysed using contour clamped homogeneous electric field electrophoresis. Southern blot hybridization with eight cloned S. cerevisiae genes (ADC1, CUP1, GAL4, LEU2, rDNA, SUC2, TRP1 and URA3) assigned to different chromosomes was used to study homology and chromosomal location of the genes in the three sibling species. A comparative study of Ty1, Ty2 and telomere-associated Y' sequences having multiple chromosomal location was also done. Chromosome length polymorphism was found in cultured strains of S. cerevisiae. Wild S. cerevisiae and S. paradoxus strains yielded chromosome banding patterns very similar to each other. The karyotype pattern of S. bayanus was readily distinguishable from that of S. cerevisiae and S. paradoxus. Southern blot analysis revealed a low degree of homology between the S. cerevisiae genes studied and the corresponding S. paradoxus and S. bayanus genes. The number of chromosomes appears to be 16 in all three species. PMID- 1441741 TI - Development of the yeast Pichia pastoris as a model organism for a genetic and molecular analysis of peroxisome assembly. AB - We describe the isolation of mutants of the yeast Pichia pastoris that are deficient in peroxisome assembly (pas). These mutants of P. pastoris can be identified solely by their inability to grow on methanol and oleic acid, the utilization of which requires peroxisomal enzymes, and are defined by the absence of normal peroxisomes as judged by electron microscopy and biochemical fractionation experiments. These mutants are the result of genetic defects at single loci and represent at least eight different complementation groups. The isolation of pas mutants of P. pastoris by a simple screen for mutants unable to use methanol and oleic acid represents a significantly more efficient method for identification of pas mutants than is possible in other organisms. To exploit this advantage fully we also developed new reagents for the genetic and molecular manipulation of P. pastoris. These include a set of auxotrophic strains with an essentially wild-type genetic background, plasmids that act as Escherichia coli P. pastoris shuttle vectors, and genomic DNA libraries for isolation of P. pastoris genes by functional complementation of mutants or by nucleic acid hybridization. The availability of numerous pas mutants and the reagents necessary for their molecular analysis should lead to the isolation and characterization of genes involved in peroxisome assembly. PMID- 1441742 TI - A screening procedure for the intracellular expression of native proteins by Saccharomyces cerevisiae: discrimination of diphtheria toxin-resistant mutants. AB - A general method is described for screening Saccharomyces cerevisiae colonies for the intracellular expression of native proteins. Colonies are replicated onto nitrocellulose membranes and yeast cell walls are removed enzymatically. The resulting spheroplasts are rapidly lysed by placing chromatography paper soaked in hypotonic buffer on the membranes. Intracellular proteins released by spheroplast lysis are bound in situ to the nitrocellulose under non-denaturing conditions and potentially can be examined using enzymatic or immunologic methods. For example, in the present study colonies were screened for the presence of elongation factor 2 (EF-2) that can be [32P]ADP-ribosylated by diphtheria toxin and [32P]NAD+. Recognition by the toxin requires the presence in EF-2 of the unique post-translationally modified histidine derivative, diphthamide. The procedure described here reliably discriminates between wild type yeast colonies and mutant colonies that do not synthesize diphthamide. In addition to facilitating the study of diphthamide biosynthesis in yeast, the more general application of this procedure will enable the screening of colonies with assays that require native proteins. PMID- 1441743 TI - Yeast flocculation: receptor definition by mnn mutants and concanavalin A. AB - Yeast flocculation involves the binding of surface lectins on flocculent yeasts, to carbohydrate receptors present as constituents of yeast cell walls. Receptors were investigated by coflocculation of flocculent strains of Saccharomyces cerevisiae, of both Flo 1 and NewFlo phenotypes, to known mnn mutants which vary in the wall mannan structure. Strong coflocculation was found with mnn1, mnn4, mnn9 and control strains, while very little coflocculation was found with mnn2 and mnn5 strains. In contrast, aggregation of these mutants by concanavalin A, a lectin with similar sugar inhibition to NewFlo phenotype flocculation, showed strong aggregation of mnn1, mnn4 and mnn5 strains and poor aggregation of mnn2 and mnn9 strains. The mmn mutant data suggested that flocculation receptors were the outer-chain mannan side-branches, two or three mannose residues in length, confirming an earlier theory based on sugar inhibition data. The similarities and differences between flocculation and concanavalin A aggregation are discussed. PMID- 1441744 TI - Mutational analysis of Schizosaccharomyces pombe U4 snRNA by plasmid exchange. AB - We have developed a system for testing mutations by plasmid exchange in the fission yeast Schizosaccharomyces pombe. This system has been used to test the requirement for different regions of the small nuclear RNA U4 in S. pombe. Surprisingly, five of seven deletion and substitution mutations tested in different regions of U4 prevent the accumulation of the mutant RNA. Substitution of the U4 sequence in stem 1 of the U4/U6 interaction domain allows accumulation of the mutant U4, but does not support viability. Two sequences with homology to the Sm binding site are found in the 3' region of S. pombe U4; substitution of the 3' sequence of the two does not interfere with accumulation or function of U4, indicating that the 5' sequence is the functional Sm-binding site. PMID- 1441745 TI - The telomere-associated MAL3 locus of Saccharomyces is a tandem array of repeated genes. AB - Saccharomyces strains capable of fermenting maltose contain any one of five telomere-associated MAL loci. Each MAL locus is a complex of three genes encoding the three functions required to ferment maltose: maltose permease (GENE 1), maltase (GENE 2) and the MAL trans-activator (GENE 3). All five loci have been cloned and all are highly sequence homologous over at least a 9.0 kbp region containing these GENEs (Charron et al., Genetics 122, 307-331, 1989). Our initial studies of strains carrying the MAL3 locus indicated the presence of linked, repeated MAL-homologous sequences (Michels and Needleman, Mol. Gen. Genet. 191, 225-230, 1983). Here we report our analysis of the centromere-proximal MAL3 linked sequences and show that the complete MAL3 locus spans approximately 40 kbp and consists of tandemly arrayed, partial repeats of the three GENE sequences described above. In addition, the structure of the MAL3 locus is compared to that of three partially functional alleles of MAL3. These alleles were shown to contain only MAL31 and MAL32 and their structure suggests that they resulted from MAL3 deletions removing the sequences centromere-proximal to MAL31. The amplification and rearrangement of the telomere-linked MAL3 sequences are discussed in the context of studies on other telemere-associated sequences from yeast and other species. PMID- 1441746 TI - Efficient selection of phleomycin-resistant Saccharomyces cerevisiae transformants. AB - The recently described dominant yeast marker Tn5ble confers phleomycin resistance on the yeast Saccharomyces cerevisiae (Gatignol, Baron and Tiraby, 1987. Mol. Gen. Genet. 207, 342-348). Incubation in non-selective medium prior to selection is critical, however, for getting phleomycin-resistant transformants. A 6-h incubation period was found to give optimal transformation frequencies, up to 10(5) transformants/micrograms plasmid, comparable to selection for uracil prototrophy (Ura+). PMID- 1441747 TI - Mapping of two new codon-specific suppressors in Saccharomyces cerevisiae. PMID- 1441748 TI - Nucleotide sequence of D10B, a BamHI fragment on the small-ring chromosome III of Saccharomyces cerevisiae. PMID- 1441749 TI - MOL1, a Saccharomyces cerevisiae gene that is highly expressed in early stationary phase during growth on molasses. AB - We have isolated a new Saccharomyces cerevisiae gene, MOL1, that is transiently expressed at high levels in the early stationary phase of batch cultures growing on industrial molasses medium. The DNA sequence of the MOL1 gene (for MOLasses inducible) with its flanking regions was determined (EMBL accession number X61669). It encodes a polypeptide of M(r) 35 kDa that is closely related to stress-inducible proteins of similar size from two Fusarium species. Unlike ST135 of Fusarium, MOL1 is not induced by ethanol or heat shock. MOL1 expression is absent in rich (YP) medium, and only very low levels of expression are detectable in minimal (YNB) medium. The gene is not essential, and a MOL1 disruption strain showed no apparent phenotype under a variety of growth conditions. The 5' region of MOL1 contains the complete sequence previously determined for the SUF4 locus, encoding a tRNA-gly (UCC) gene, which has been mapped to chromosome VII. PMID- 1441750 TI - RHO gene products, putative small GTP-binding proteins, are important for activation of the CAL1/CDC43 gene product, a protein geranylgeranyltransferase in Saccharomyces cerevisiae. AB - Two multicopy suppressors of the cal1-1 mutation in the yeast Saccharomyces cerevisiae have been isolated and characterized. They are identical to the yeast RHO1 and RHO2 genes, which encode putative small GTP-binding proteins. Multiple copies of either RHO gene suppressed temperature-sensitive growth of the cal1-1 mutant but did not suppress the cal1 null mutant. Genetic analysis suggests that overproduction of either RHO gene product acts for activation of the CAL1 gene product. PMID- 1441751 TI - Disruption and mapping of IDI1, the gene for isopentenyl diphosphate isomerase in Saccharomyces cerevisiae. AB - Isopentenyl diphosphate isomerase catalyses an essential activation step in the isoprene biosynthetic pathway. The Saccharomyces cerevisiae gene for isomerase, IDI1, was recently isolated and characterized (Anderson et al. J. Biol. Chem. 1989a, 264, 19169-19175). Wild-type IDI1 was disrupted with a LEU2 marker, and the resulting DNA was used to transform a yeast leucine auxotroph. Southern blots of EcoRI fragments of chromosomal DNA from the diploid strain showed the expected fragments for intact and disrupted IDI1. Dissection and analysis of tetrads demonstrated that IDI1 is an essential single-copy gene. A CHEF gel and clone grid filter analysis, followed by chromosomal mapping indicated that the gene is located on chromosome XVI approximately 55 kb centromere proximal to PEP4. PMID- 1441752 TI - DNA sequencing and analysis of a 24.7 kb segment encompassing centromere CEN11 of Saccharomyces cerevisiae reveals nine previously unknown open reading frames. AB - A 24.7 kb segment of the cosmid clone pUKG047 containing a Sau3AI-partial fragment from the centromere region of Saccharomyces cerevisiae chromosome XI was sequenced and analysed. A mixed strategy of directed methods including exonuclease III nested deletion, restriction fragment subcloning and oligonucleotide-directed sequences was carried out. Exclusive use was made of the Applied Biosystems Taq DyeDeoxy Terminator Cycle technology and a laser-based AB1373A sequencing system for reactions, gel electrophoresis and automated reading. A total of 12 open reading frames (ORFs) was found. Nine new ORFs (YK102 to YK110) were identified, three of which (YK102, YK107, YK108) showed homologies to proteins of known function from other organisms. In addition, sequence analysis revealed three recently functionally characterized genes (MET14, VPS/SPO15, PAP1), which could be joined to the earlier published CEN11 region. PMID- 1441753 TI - Sequence of a 12.7 kb segment of yeast chromosome II identifies a PDR-like gene and several new open reading frames. AB - A 12,684 bp DNA fragment, between FUS3 and the centromere, from the left arm of chromosome II of Saccharomyces cerevisiae was sequenced as part of the European project to sequence the whole chromosome. This segment contains at least five complete new open reading frames (ORFs) and the beginning (191 first 5' codons) of an ORF whose putative translational product is highly similar to the multidrug resistance PDR1 gene previously characterized by Balzi et al. (1987) on chromosome VII. PMID- 1441754 TI - An 11.4 kb DNA segment on the left arm of yeast chromosome II carries the carboxypeptidase Y sorting gene PEP1, as well as ACH1, FUS3 and a putative ARS. AB - We report the nucleotide sequence of an 11.4 kb DNA segment from the left arm of Saccharomyces cerevisiae chromosome II. This sequence contains a typical structure of a functional ARS as well as five open reading frames (ORFs) longer than 300 bp. One is PEP1, a gene encoding a transmembrane protein of 1579 amino acids which transits through the secretory pathway and is involved in vacuolar protein sorting. Two genes were previously sequenced: ACH1 (Lee et al., 1990) and FUS3 (Elion et al., 1990), which encode an acetyl-CoA hydrolase and a protein kinase involved in the cell division cycle, respectively. The last two ORFs localized on the complementary strand of ACH1 are not likely to be expressed. PMID- 1441755 TI - AFG1, a new member of the SEC18-NSF, PAS1, CDC48-VCP, TBP family of ATPases. AB - We have sequenced a gene that encodes a 377 amino acid putative protein with an ATPase motif typical of the protein family including SEC18p (NSF = N-ethyl maleimide-sensitive fusion protein; vesicle-mediated endoplasmic reticulum to Golgi protein transfer), PAS1p (peroxisome assembly), CDC48p (VCP = valosin containing protein; cell cycle) and TBP1 (Tat-binding protein). This gene, AFG1 for ATPase family gene, also has substantial homology to these proteins outside the ATPase domain. AFG1 is located on chromosome V immediately centromere proximal to MAK10. PMID- 1441756 TI - Sequence of the genes encoding subunits A and B of the vacuolar H(+)-ATPase of Schizosaccharomyces pombe. AB - The genes encoding subunits A (vma1) and B (vma2) of the vacuolar H(+)-ATPase from Schizosaccharomyces pombe were cloned by hybridization to cDNAs of the homologous genes in Neurospora crassa. Both genes are interrupted by introns, two in vma1 and four in vma2. Positions of introns do not appear to be conserved when compared to those of N. crassa. The subunit A gene encodes a single product of 619 amino acids and is not interrupted by the coding sequence for a second product as found for Saccharomyces cerevisiae (Kane, P. K., Yamashiro, C. T., Wolczyk, D. F., Neff, N., Goebl, M., and Stevens, T. H. (1990). Science 250, 651 657). PMID- 1441757 TI - LEU2 gene homolog in Kluyveromyces lactis. AB - A DNA fragment that can complement the leu2 mutation of Saccharomyces cerevisiae was cloned from the genomic library of Kluyveromyces lactis. The nucleotide sequence revealed an open reading frame of 362 codons, 75% homologous to S. cerevisiae LEU2 gene. The upstream region contained a CCGGAACCGG sequence identical to the site of leucine-specific control of LEU2. Further upstream, there is a partial open reading frame homologous to rat ribosomal protein L7. PMID- 1441758 TI - Saccharomyces cerevisiae contains a homolog of human FKBP-13, a membrane associated FK506/rapamycin binding protein. PMID- 1441759 TI - [Determination of water-soluble vitamins B1, B2, B6 and B12 in milk using HPLC]. AB - Simple methods of determining the water-soluble vitamins B1, B2, B6 and B12 in milk by HPLC are described. Compared to existing procedures, the following improvements can be realized. The oxidation of vitamin B1 to thiochrome is stopped by the addition of sodium sulphite. This step significantly increases repeatability. Thiochrome is then extracted with butan-1-ol, which results in fewer co-extracts and greater selectivity. After the hydrolysis of the 5 phosphates of the vitamin B6 (pyridoxine, pyridoxal and pyridoxamine), these three vitamers are determined by isocratic HPLC as DDS-ion-pairs and with fluorimetric detection. As only microbiological methods have so far been used for the determination of minute quantities of vitamin B12 in milk, a new HPLC procedure is proposed with a detection limit of 0.2 micrograms vitamin B12/L milk. PMID- 1441760 TI - A rapid, sensitive and economic method for the detection, quantification and confirmation of aflatoxins. AB - A rapid, sensitive and economic method for the detection, quantification and confirmation of aflatoxins is described. Aflatoxins B1, B2, G1, and G2, are extracted by methanol/water (85 + 15) and partitioned into methylene dichloride. The methylene dichloride solution is cleaned up on a polypropylene column, filled with 0.5 g silica gel 60. The aflatoxins are eluted with chloroform-acetone (90:10) and are detected using bidirectional thin-layer chromatography (TLC) with aluminium silica gel foil. The mean recovery of aflatoxins B1, B2, G1, and G2 in corn samples was 73, 78, 80, and 64%, respectively; the limit of detection was 0.5 micrograms/kg. The results can also be confirmed by derivative formation using trifluoroacetic acid on the TLC plate. The method has been applied to a wide range of foods with good results. PMID- 1441761 TI - Rapid analysis of whey proteins from different animal species by reversed-phase high-performance liquid chromatography. AB - This paper explores the possibilities of reversed-phase high performance liquid chromatography (RP-HPLC) for analysing whey proteins from the milk of cows and other animal species. An RP-HPLC method is proposed to separate and quantify bovine whey proteins. Using this method, bovine serum albumin, alpha-lactalbumin, beta-lactoglobulin A and beta-lactoglobulin B were separated in less than 7 min. It is demonstrated that irreversible adsorption of bovine whey proteins occurs on unused columns (i.e. those not previously used to separate proteins). Therefore, prior conditioning of the column with whey proteins is required for valid protein quantification. Conditioning can be achieved by eluting a large amount of at least one of the bovine whey proteins through the unused column. The calibration curve (peak area vs. protein concentration) for the main bovine whey proteins was linear. This method also allowed good separation of caprine and ovine whey proteins and separation of some homologous whey proteins of different animal species. Detection of milk mixtures from different animal species was carried out using this method. PMID- 1441762 TI - [Recent advances in neuropsychopharmacology of the central serotonin receptor]. AB - The existence of multiple serotonin (5-HT) receptor subtypes has been proposed based on radioligand binding assay technique and other functional assay. Recent advance of neuropsychopharmacology has contributed to elucidating their physiological functions, ranging from molecular biological to clinical characteristics. Abnormalities of central 5-HT function are currently thought to play a significant role in mental disorders such as affective disorder, anxiety disorder, eating disorder and negative symptoms of schizophrenia, and in the regulation of physical functions such as body temperature, blood pressure and pain. The most significant outcome of the basic pharmacological work has been successful application of 5-HT receptor agents to the treatment of the above clinical disorders. In this article, the authors review the history of 5-HT receptor research and the role of 5-HT receptor in clinical disorders. PMID- 1441763 TI - [Patch-clamp technique]. AB - We first describe how to set up the system for patch-clamp recording and carry out the experiments with 4 different modes of conventional patch-clamp technique: cell-attached, whole-cell, inside-out and outside-out configurations. Thereafter, we mention about an improved 'nystatin perforated' patch-clamp technique which dissolves the fault of conventional patch-clamp techniques except the cell attached mode. PMID- 1441764 TI - Differential effects of intracerebroventricular AF64A injection, nucleus basalis of Meynert lesion, and scopolamine on place navigation and open-field behavior of rats. AB - The present study was conducted to compare the behavioral effects of intracerebroventricular AF64A injection, electrolytic lesion of the nucleus basalis of Meynert (NBM), and systemic scopolamine treatment, all of which are typical experimental models of central cholinergic system dysfunction, on place navigation performance and open-field behavior in rats. The animals were trained in a circular pool to escape from opaque water onto the hidden platform fixed at a particular location for 5 days. Significant performance deficits were observed in all the models tested. However, it is of importance that any impairments relating to information storage within a day or across days were not obtained. Choline acetyltransferase activity was decreased in the hippocampus of AF64A injected rats and in the cortex of NBM-lesioned rats, respectively, but those changes did not simply associate with the reductions of the performance. These results suggest that the central cholinergic system is only partially involved in cognitive process. In the open-field test, ambulation, rearing, defecation, and urination were measured for 5 min. Patterns of changes in the open-field behavior were clearly different among the 3 models, indicating variability of the effects of these cholinergic manipulations on motor activities and emotionality. PMID- 1441765 TI - [Effects of mesocortical dopaminergic lesions on stress-induced changes in monoamine metabolism in the discrete brain regions of rats]. AB - This study assessed the possible influence of the mesocortical dopamine (DA) system on the reactivity of subcortical monoamine systems to stress. Rats were either sham-operated or subjected to DA-depleting lesions of the medial prefrontal cortex (mPFC) with 6-hydroxydopamine. Fourteen days after surgery, the rats were exposed to 30 or 60 min immobilization stress, and levels of noradrenaline, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). DA, 3-4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin, and 5 hydroxyindoleacetic acid were measured in nine brain regions. The stress caused a significant increase in the levels of DA metabolites, DOPAC or HVA, in the mPFC of sham-operated, but not of lesioned animals. HVA concentrations in the nucleus accumbens, olfactory tubercle, and ventral tegmental area were significantly increased in both sham-operated and lesioned rats, but the effect of stress on the subcortical DA systems was unaffected by the lesion. The stress also significantly elevated MHPG levels in the amygdala and hypothalamus of both groups of animals, and these results were similar in the amygdala of rats with or without lesions. In the hypothalamus, however, 60 min stress caused a more marked increase in MHPG concentrations in lesioned rats than in sham-operated rats (lesion-group, 143%; sham-group, 122%), while 30 min stress produced a similar elevation in both groups of animals (lesion-group, 149%; sham-group, 142%). These results suggest that the mesocortical DA system may modulate the sensitivity of the noradrenergic system in the hypothalamus to stress. PMID- 1441766 TI - [Early history of the specialist in psychotherapy medicine]. PMID- 1441767 TI - [Quality assurance: clarification of a provocative and trendy expression]. AB - The GRG from 1988 commits all suppliers of medical or therapeutic services in Germany to take steps to assure quality. The legislator left it in the care of the involved parties to find an agreement how to do it. This vagueness together with the emphasis put simultaneously on quality and economy turned this issue into a threat for many therapists. This tendency is supported in addition by the intensified competition between the therapeutic schools. The major goal of this review is to give some information that provide a functional discussion and hinder a misuse. The article informs about the issue of quality assurance, which is not as new as some people may consider it; the political context is pointed out, the main concepts are introduced, approaches and experiences from other countries or other fields of medicine are reported, and the conflicts between the interest groups are sketched out. Finally, some comments on central aspects are given which eventually make easier a transference into the field of psychotherapy and hopefully encourage specific approaches of quality assurance in this field. PMID- 1441768 TI - [Disillusionment as a change: 3 progression steps in female development]. PMID- 1441769 TI - [The Harald Schultz-Hencke intentionality concept from the viewpoint of psychoanalytic infant research]. AB - Recent Research on small children has infused Schultz-Hencke's concepts of intentionality and the experiencing of drives with new relevance. Because of the fundamental similarities between Schultz-Hencke's work and psychoanalytical infant research, Lichtenstein's theory of motivation is being compared to Schultz Hencke's experiencing of drives. PMID- 1441770 TI - [Psychotherapy of depressed elderly patients with pathologic grief reaction]. AB - Loss events not sufficiently worked through frequently are the core syndrome of depressive illness in the elderly. The frequency and symptom pattern of pathological grief reactions as well as influencing factors in 155 patients 60 year old or older treated for endogenous, neurotic and reactive depression, are described. Special issues of the psychodynamics of pathological grief reactions in the elderly are discussed; problems of counter-transference are pointed out. The developmental potential in the elderly often is underestimated. Psychotherapy of pathological grief reactions in the elderly offers important and rarely used possibilities. PMID- 1441771 TI - [Elderly patients in psychosomatic psychotherapeutic institutions]. AB - With the aid of a comparative study of the data collected in the Berlin Psychotherapy Study and the outpatient clinic of the Psychosomatic Clinic (University of Heidelberg), the allocation and utilization modalities of elderly patients with regard to psychosomatic-psychotherapeutic institutions is investigated. One important result seems to be the high rate of psychodynamically understandable triggering situations (as a measurement of psychological comprehension of the symptoms) and the consequent therapy recommendations (as a measurement of treatability) even for elderly patients. A case study will demonstrate that the danger may arise to subsume new somatic symptoms in the elderly under the aspect "multimorbidity" and thus withhold recommended psychotherapeutic treatment. PMID- 1441773 TI - Thermal deactivation kinetics of CM-cellulase from a local isolate of Aspergillus niger (RD-2231). AB - The kinetic of thermal deactivation of CMC-ase activity of A. niger, locally isolated, was studied. The enzyme was found to be more stable in temperatures below 40 degrees C. The rates of activity decay were significant at high temperatures and can be described as a first-order kinetic model. Deactivation rate constants (Kd) were determined at different temperatures (30, 40, 55 and 65 degrees C). Kd value for CMC-ase activity decay at 65 degrees C was 28 times higher than its value at 30 degrees C. An Arrhenius type temperature dependence of Kd was found, and the activation energy (Ea) of the thermal deactivation was calculated to be 8400 cal/mole. Thermodynamic quantities (delta H) and (delta S) for deactivation process were 7700 and 11.9 cal/mole, respectively. The change of two kinetic parameters, i.e. Vmax and Km under deactivation conditions, was discussed. PMID- 1441772 TI - [Psychotherapy with elderly patients. Experiences from a psychiatric psychotherapeutic consultation service]. AB - Experiences with psychoanalytically oriented psychotherapy with the elderly have been made in a psychiatric consultation service at a general hospital. The life long importance of psychodynamically relevant conflicts is illustrated by two case examples of psychosomatic patients with asthma and functional symptoms of the gastrointestinal tract. The experiences with short-time psychotherapies described here are encouraging and confirm results of other groups demonstrating the efficiency of psychotherapeutic interventions with the elderly. Special problems of psychotherapy with older patients in a psychiatric consultation service and implications for the routine medical treatment of general-hospital patients are discussed. PMID- 1441774 TI - Physiological and biochemical characteristics of staphylococci isolated from the rumen of young calves and lambs. AB - Six strains of rumen ureolytic staphylococci were isolated from young calves and lambs. Three isolates were allotted to the species Staphylococcus xylosus. Staphylococcus saprophyticus and Staphylococcus gallinarum. The taxonomy of remaining three isolates was uncertain. Total numbers of staphylococci varied between 10(4) and 10(6) per 1 ml of the rumen fluid. Rumen Staphylococci utilized a wide range of substrates and produced a bacteriocin-like substance. No strain hydrolysed gelatin. All strains produced catalase and reduced nitrate. The main product of anaerobic carbohydrate metabolism was lactate accompanied by formate, acetate and ethanol. Most of strains were sensitive to ionophores, avoparcin, bacitracin and tylosin. All strains were sensitive to rifampicin, tetracycline and chloramphenicol. PMID- 1441775 TI - [Sources and developments in heart surgery]. AB - This contribution deals with the development of the individual ramifications of cardiac surgery from their inception to the presence and especially highlights the personalities responsible for these breakthroughs. The trials and errors of these developments are described along with the multitude of presently unanswered questions including those related to thoracic organ transplantation, cardiac assistance, and replacement as well as the socio-economical aspects of modern cardiac surgery. PMID- 1441776 TI - [Use of hypertonic NaCl solutions in primary volume therapy]. AB - The i.v. bolus infusion of 4 ml/kg b.w. of hypertonic (7.2-7.5%) saline solution represents a new concept for primary resuscitation from traumatic-hemorrhagic shock; it is called "small-volume resuscitation". Experimental studies have demonstrated that for the case of a 50% blood loss the infusion of 7.2-7.5% NaCl in a dose equivalent to 1/10 of the blood loss effectively restores cardiac filling pressures and cardiac output and significantly increases systemic pressure. Simultaneous application of a colloid (6-10% Dextran 60/70; 6-10% HAES 200,000/0.5) prolongs the circulatory effect of the hypertonic solution. Moreover, "small-volume resuscitation" by means of 7.2 NaCl/10% Dextran 60 was shown to completely restore nutritional organ blood flow already within only 5 minutes. The superiority of "small-volume resuscitation" using hypertonic hyperoncotic solution as compared to conventional volume therapy consists of its effects on the microcirculation. Recent clinical trials have revealed the efficacy, practicability and safety of this new therapeutic concept for primary resuscitation from trauma and shock. PMID- 1441777 TI - [Duplex sonographic monitoring of infra-inguinal arterial reconstructions: can a threatened bypass occlusion be detected by this method?]. AB - In our institution, 95 infrainguinal arterial reconstructions were prospectively entered into a graft surveillance programme which consisted of a postoperative i.a. DSA and routine assessment of graft flow velocity (GFV) and ankle pressure indices (ABI) during the first postoperative year. An average of 4.1 GFV measurements was obtained during a mean follow-up period of 8.2 months. Abnormal GFV led to arteriography in 29 bypasses identifying--aside from three false positive findings--two graft occlusions and 24 severe (> 70%) graft stenoses. Of the latter, in only 7 cases a significant decrease in ABI was found. Unheralded graft occlusion occurred in 6 patients. Including the corrections of the above mentioned lesions, secondary patency rates were 97% at 30 days and 89% at one year. PMID- 1441778 TI - [The elderly as heart surgery patients. Pre- and postoperative analysis of the quality of life]. AB - The aim of the study was to measure pre- and postoperative quality of life of the old patient to find out his profit of open heart surgery. METHOD: 71 patients ranging from 75 to 86 years (mean 77.6 years) were examined by using a standard interview about their quality of life on the day of hospital admittance and one year after returning home (range 11-14 months). RESULTS: There was an improvement of postoperative quality of life. These results were similar to data reported in the literature after investigating younger patients. CONCLUSION: No one should be excluded from open heart surgery because of old age. PMID- 1441779 TI - [Shouldice hernia report with a PTFE suture]. AB - Between 4/90 and 2/91 we repaired 105 inguinal hernias according to Shouldice's technique. Instead of an absorbable suture (PDS no.0) we used a PTFE suture no.0. By this study we tried to assure that it is allowed to use as well the non resorbable PTFE suture no.0. in hernia repair as the slowly resorbable PDS suture no.0. We compared the rate of postoperative hematomas, seromas and pus collections and the rate of early recurrences in both groups. The results of the PTFE group were compared with those of a prospective study (n = 100) between 6.88 and 4.89 when we used PDS suture no 0. In the PTFE group we saw 9.5% hematomas, 1.9% seromas and 0.9% pus collections. In the PDS group 4% of the patients developed a hematoma, 4% a seroma and 2% a pus collection. We saw 1.9% early recurrences after 8 months (PTFE: 7-11; median: 9 months) and 3.2% after 9 months (PDS: 8-13; median: 10 months) medium follow-up time. The results did not significantly differ between both groups. (Chi-square test: p = 1.0). By these results we can draw the following conclusions: 1. The use of a non absorbable PTFE suture no 0 in hernia repair is of no disadvantage. 2. The principle of hernia repair is the induction of scar tissue in the site of hernioplasty; the use of slowly resorbable suture material is allowed as well. PMID- 1441780 TI - [Perforated aneurysm of the left hepatic artery]. AB - Aneurysms of the hepatic artery are second (20%) to the splenic artery the most common site of splanchnic artery aneurysms. The frequency of location in the branches of the hepatic artery is as follows: common hepatic 63%, right hepatic 28, left hepatic 5%, both left and right hepatic artery 4%. Today atherosclerosis (30 - 32%) is the most prevalent etiology, followed by trauma (22 - 28%) and inflammatory lesions (11%). The average age is 41,6 years, the male to female ratio 2:1. In 64-80% of patients rupture of the aneurysm is the first and dramatic clinical manifestation. The mortality is then about 35%. The case of a 64 years old female with perforated aneurysm of the left hepatic artery is presented and the literature is reviewed with emphasis on etiology, clinical manifestation, diagnostic and therapeutic (surgical and non-surgical) procedures. PMID- 1441781 TI - [Post-traumatic hemobilia and successful direct treatment of the arteriobiliary fistula]. AB - Traumatic hemobilia is a rare complication of deep and central liver injuries. Repeated and massive bleeding requires an active therapy. For diagnosis of the arterial-biliary fistula, most advantageous is a transcutaneous selective arteriography which can be used also for therapeutic embolization. Of surgical techniques, ligature of the art.hepatica comm. or propria and direct closure of the fistula in the liver parenchyma are recommended. The authors report on such a successful direct intervention in a 9-year-old girl. PMID- 1441783 TI - [Pioneer interventions in surgery and their legal background]. PMID- 1441782 TI - [Malignant tumor of the autonomic nervous system of the stomach (GAN-tumor)--case report of a new entity]. AB - Gastrointestinal autonomic nerve (GAN)-tumors are extremely rare. So far seven cases of intestinal and four of gastric GAN-tumors were reported. GAN-tumors, also termed plexosarcomas, arise from autonomic nervous system plexuses of the gastrointestinal tract such as those of Meissner or Auerbach. We report a case of a metastatic gastric GAN-tumor in a 40-year-old woman. A small, 1 cm in diameter, submucosal plexosarcoma located in the posterior gastric wall and a 1.5 kg, 23 x 15 x 11-cm metastasis located retroperitoneally behind the stomach between liver, spleen and pancreas without discernable invasion of any of these organs were found. En-bloc resection of the retroperitoneal mass, the spleen, the pancreatic tail, and a part of the posterior gastric wall adhering to the mass were performed. In addition, lymph node metastases in splenic hilum were noted, and resected. In CT scan liver metastases were detectable fourteen months after surgery. The diagnosis is based on light microscopical, ultrastructural, and immunhistochemical analyses. The prognosis of GAN-tumors is fatal. In spite of radical excision 8 of 11 reported patients died few month after surgery while local recurrences and/or metastases in regional lymph nodes and in the liver were found. The response to chemotherapy was poor. PMID- 1441784 TI - [Sequential cancer of concomitant cancer?]. AB - The generally-favoured polyp-cancer sequence hypothesis its probably wrong. The distribution of polyps in large intestine differs from that of cancer. There is evidence that different aetiological factors are involved in the genesis of polyps, their growth rate and the development to invasive cancer. Most polyps are very small (90%). They never develop a cancer. It is a diffusely abnormal state of the large bowel mucosa which renders it more liable to produce often polyps and very rare carcinoma (5%). Polyp-carcinoma concomitance is much nearer to the truth. PMID- 1441785 TI - [The dysplasia-carcinoma sequence in the colorectum]. AB - The concept of dysplasia-carcinoma sequence has been established for the gastrointestinal tract. Dysplasia is defined as unequivocal neoplastic proliferation of epithelium without invasion and represents the precancerous lesions of the colon and rectum. The most common appearance of dysplasia is polypoid adenoma, however, flat adenomas are increasingly diagnosed. During the last 20 years, new pathological and biological methods including molecular genetics showed the stepwise evolution of colorectal carcinoma from normal mucosa to dysplasia of increasing grade and to invasive carcinoma. Of course, dysplasia carcinoma sequence does not imply the development of carcinoma in every focus of dysplasia. In fact, the incidence of carcinomas from adenomas is 5-10%. A new molecular or genetic epidemiology promises an improved selection of high risk individuals. PMID- 1441786 TI - [Symptomatic stenoses following stapler anastomosis of the large intestine]. AB - Since 1978 the stapled colonic anastomosis belongs to the technical standard in surgery of the rectosigmoid. It is followed by an extension of indications for sphincter-preserving excisional treatment. The main advantages of the mechanical suturing are the shortening of operation time as well as the practical and easy management, especially when the anastomosis is located low in the pelvis. Early respectively late postoperative strictures represent the most frequent complications of stapled anastomosis. From 1989 to 1991, the stapling technique was used for colorectal anastomosis in 196 cases in our hospital. Clinical stenosis occurred in 5 cases, an incidence of 2.5%. Causative the size of the cartridge, the healing by second intention because of the metallic staples, a disturbed microcirculation depending on the tension around the anastomosis, missing normal fecal dilation because of protective colostomy and an incongruity of the combined lumina are discussed. Independent of localisation and grade of the stricture, repeated dilation was a successful therapy in all 5 cases. PMID- 1441787 TI - [Minimally invasive surgery of the rectum]. AB - Low precision of transanal techniques, their limited area of application and high rate of complications of extensive surgical techniques led to the development of an endoscopic surgical system. Its main indication is the removal of broad based adenomas and early rectal cancers. Further indications are palliative excisions of advanced cancers. From July 1983 till December 1990 the endoscopic system has been employed on 233 patients. The total sum of operations raised to 251 cases due to recurrences and new tumour formations. The overall crude 5 year survival with merely local removal of rectal cancer was 67% for early rectal carcinoma patients and 75% for patients with pT2 carcinomas. Early postoperative complications consisted of 5 intraperitoneal perforations, 4 recto-vaginal fistulas and 4 haemorrhages (complication rate 5.2%). There were 2 postoperative deaths due to cardiopulmonary failure (clinical lethality 0.8%). The overall recurrence rate of adenomas was 4.9%. In accordance with the selection criterias of other authors, our selection criteria for curative local excisions of rectal cancers enclose tumour diameter less than 4 cm, pT1 carcinomas, low grade malignancy and tumour free margins of locally excised specimen. PMID- 1441788 TI - [Delay phenomenon of the jejunum. Studies of nutritional blood supply and oxygen supply of the jejunum of the rabbit]. AB - INTRODUCTION: Delay procedure has been shown to effectively improve microvascular perfusion in skin flaps. In analogy to skin, we have analyzed the effect of delay on regional blood flow and surface tissue PO2 of a proximal segment of the jejunum. METHODS: Under nembutal anesthesia (30 mg/kg BW) and mechanical ventilation a total of 15 rabbits were laparotomized. Regional blood flow of the jejunum was estimated using radioactive-labeled microspheres, and tissue PO2 was assessed by means of a platinum-multiwire surface electrode. In order to induce acute ischemia three consecutive jejunal arteries were ligated, and the proximal marginal vascular arch was temporarily occluded by a microvascular clip. Delay procedure was induced by 1) ligation of the jejunal arteries, 2) in situ maintenance of the jejunal segment for two weeks followed by 3) relaparotomy and occlusion of the proximal marginal arch (n = 8). Regional blood flow of the jejunum and tissue PO2 were also assessed in sham-operated animals (n = 7). RESULTS: After acute ischemia regional blood flow (0.27 (0.05) ml x min-1 x g-1, mean (SEM)) and surface tissue PO2 (39 (3) mmHg) of the jejunal segment were found significantly (p < 0.05) reduced as compared to baseline (0.82 (0.12) ml x min-1 x g-1 and 66 (1) mmHg) and sham-operated animals (0.69 (0.12) ml x min-1 x g-1 and 62 (5) mmHg), respectively. In contrast, delay of the jejunal segment resulted in almost complete preservation of regional blood flow (0.56 (0.04) ml x min-1 x g-1) and surface tissue PO2 (65 (1) mmHg). CONCLUSION: We therefore like to propose that the jejunal delay phenomenon may be clinically used to reduce ischemic complications in jejunal transposition for esophagoplasty. PMID- 1441789 TI - [Status of treatment with free radical scavengers following kidney and pancreas transplantation]. AB - AIM OF THE STUDY: The frequency of acute renal failure (ARF) after preservation and kidney transplantation is rather high. The etiology of an ARF is an interaction of multiple mechanisms as donor conditions, explantation procedure, duration of ischemia and reperfusion injury. Different experiments demonstrated, that the damage produced by reperfusion can be prevented by the scavenger of free radicals, the enzyme superoxide dismutase (SOD). PATIENTS AND METHODS: After a double blind study, using consecutive intraarterial bovine SOD (n = 100) in kidney transplantation, showing a trend in favour to the SOD treated group, especially when long-time stored kidneys (> 30 h) had been grafted, a second study was designed to evaluate the efficiency of intravenous recombinant human SOD in the protection from ARF. This study (n = 180) was split into two different trials, double blind and randomized in itself: (A) grafts with cold ischemia time lower or equal 30 hrs., (B) cold ischemia more than 30 hrs. All grafts were preserved with Euro-collins. The study substances were either placebo or 200 mg rh-SOD (Grunenthal GmbH, FRG), given 10-2 minutes prior reperfusion intravenously. Parameters causing an ARF were equal and well comparable in both groups. RESULTS: Concerning early graft function there was no difference in study A between placebo and rh-SOD group. In study B the average and median of the day creatinine dropped the first time without interference of hemodialysis, showed a trend in favour to the rh-SOD group. If placebo was given only 19% of the grafts gained function within the first week, when rh-SOD was applied 47% functioned in the first week. The lack of significant benefit from SOD treatment could be explained by the dependency of the proportion of the total injury caused by reperfusion compared with the proportion resulting from ischemic injury per se. The rh-SOD group showed a better 3 years graft survival rate (+16%). CONCLUSIONS: It seems rh-SOD is able to augment the early graft function and is helpful to reduce the ARF frequency when long-time stored cadaveric kidneys have to be transplanted. These promising results encourage us to continue the study in protocol B to get greater numbers and definitive results. PMID- 1441790 TI - [Is penicillin G the drug of choice in gas gangrene? Results of a prospective documentation of clinical, microbiological and animal experiment data]. AB - Between 1978 and 1990 98 patients with gas gangrene were treated in the departments of general surgery and traumatology of the University of Kiel. The microbiological results of tissue samples and results of animal infectious experiments were correlated to the clinical outcome. It could be shown, that gas gangrene due to C.perfringens alone had a higher mortality than gas gangrene due to polymicrobial infection. In trauma patients, however, the rate of amputations was lower in cases of clostridial monoinfections (25%), than in patients with mixed infections (48%). The results of animal experiments with guinea pigs which were infected by patients' infectious material showed a correlation to the clinical outcome. This correlation could not bee shown using isolated and cultured clostridia. Therefore and because of the quantity of mixed infections it is necessary to use broad spectrum antibiotics for treatment in cases of gas gangrene and for perioperative antibiotic prophylaxis. Penicillin-G alone can not more be recommended for this purpose. PMID- 1441792 TI - [The surgeon Karl Thiersch as cholera research specialist]. PMID- 1441791 TI - [Heterotopic ossifications in a patient with severe craniocerebral trauma]. AB - Patients with severe head injury and fractures of joints or of long bones often show a hypertrophic callus formation which leads to a rapid consolidation of a fracture but can also lead to an ankylosis of the joints. This is the retrospective report of a patient who showed this phenomenon. PMID- 1441793 TI - [The evolutionary changes in the amino acid sequences and properties of the ATP synthase in chloroplasts, mitochondria and bacteria]. AB - Studies have been made on ATPase from chloroplasts, cyanobacteria and mitochondria of higher plants and animals. No intraspecies and interspecies variability of chloroplast and mitochondrial ATPase was found with respect to pH optimum of the activity, to specificity to cations as substrate components, to sensitivity to stimulating and inhibiting anions and ethanol, to optimal stimulating ethanol concentration. Intergenus variation of these properties of ATPase from chloroplasts, plant mitochondria, and cyanobacteria was revealed. Analysis of homology of the amino acid sequence in ATP-synthase subunits showed that ATP-synthase genes in chloroplast DNA originate from cyanobacterial genome, whereas ATP-synthase genes in plant and animal mitochondria-from genome of Rhodospirillum rubrum or closely related species. It was established that no recombination between the genetic material of chloroplasts and mitochondria took place during evolution. PMID- 1441794 TI - [The dual regulation by glucagon of the adenylate cyclase system in the embryonic chick heart]. AB - Taken in physiological concentrations, glucagon increases the activity of adenylate cyclase from the heart of 11-day chick embryos, i.e. at the earliest investigated stage. High glucagon concentrations inhibit the enzyme from cardiac membranes at all ontogenetic stages except mature chicks in which glucagon produces stimulating effect. Guanine nucleotides potentiate this effect up to the 16th day of incubation, this effect being absent at later periods. Reconstruction of adenylate cyclase system from the heart of 16-day embryos with N-proteins from mature liver tissue of chicks results in the recovery of potentiating effect. However, at later developmental stages, potentiation was absent even in the presence of N-proteins. PMID- 1441795 TI - [Testosterone production by the fetal testes of silver foxes selected for their domesticated behavior]. AB - Testosterone content was determined by radioimmune assay in the testes of silver foxes between the 31st and 50th days of gestation. Small quantities of testosterone were found in the testes already at the 31st day of prenatal life, gradually increasing up to a maximum value at the 50th day. No significant difference in testosterone content was found between domesticated and undomesticated silver foxes during prenatal life. It is suggested that selection for domesticated behaviour affects rather central control of endocrine functions than steroid biosynthesis in the testes. PMID- 1441796 TI - [The temperature hysteresis of water-salt metabolism in the frog Rana temporaria]. AB - Frogs acclimated to 4 degrees C were transported to a medium with temperature 20 degrees C, which caused polyuria; recovery of normal diuresis took about 24 h. During this period, hypernatremia was observed together with the increase in natriuresis, the rate of renal excretion of potassium ions with urea remaining constant. Water content of skeletal muscles decreased. Transportation of frogs acclimated to 20 degrees C into a medium with a temperature 4 degrees C decreased their diuresis. Renal excretion of sodium, calcium and magnesium ions remained unchanged, whereas that of potassium ions significantly decreased. The content of potassium and magnesium in the blood serum increased, that of sodium--decreased. Hydratation of muscled and kidneys was accompanied by the decrease of calcium, potassium and magnesium ions calculated per wet weight of the tissues, the level of sodium remaining unaffected. The data obtained indicate significant changes in the pattern of water and salt metabolism in frogs during temperature hysteresis. PMID- 1441797 TI - [The dynamics of the activity parameters of the neuronal populations in the dorsal hyperstriatum of hens depending on the afferent input in ontogeny]. AB - Studies have been made on the properties of neuronal populations of the dorsal hyperstriatum of the forebrain in hens beginning from the 18th day incubation up to the 7th day after hatching, which were incubated and kept either in darkness or under periodic illumination. Among the investigated parameters of multicellular activity, mean frequency of the discharge activity was found to be most susceptible to the level of external light afferentation in ontogenesis. The discharge activity was more intense in the left hemisphere of chick embryos and chicks from illuminated group, which may be associated with asymmetrical visual afferentation resulting from embryonic position within the egg, and its modulating effect on synchronization processes in the adjacent neurones of the given structure. PMID- 1441798 TI - [The temperature dependence of receptor structures and temperature-related reception]. AB - In acute experiments on rats, studies have been made on impulse activity of single fibres of n. ischiadicus evoked by stimulation of the receptive fields of the sole by focused ultrasound. Mechanical effects were produced by rectangular ultrasonic stimuli, thermal ones--by trapezoid ones. With respect to the magnitude of a threshold response to a rectangular stimuli, the receptor structures were divided into three groups, i.e. low, mean and high threshold ones. Low and mean threshold receptor units responded to local thermal stimulation. Mean threshold units exhibited an increase of the threshold to mechanical stimulation after local thermal one. In human subjects, the structures which are functionally similar to mean threshold units, evoke thermal sensations, and may be classified not only as temperature dependent, but also as temperature sensitive. PMID- 1441799 TI - [The genetic and sexual differentiation of the brain]. PMID- 1441800 TI - [The code of codon roots--the evolutionary basis of protein structures and functions]. PMID- 1441801 TI - [The seasonal dynamics of the adenine nucleotide level in the liver mitochondria of the frog Rana temporaria]. AB - ATP, ADP and AMP content of liver mitochondria has been determined in frogs immediately after isolation during autumn, winter and spring periods. Seasonal changes in adenine nucleotides in frogs are similar to those observed in rat liver mitochondria during early postnatal ontogenesis. It is suggested that in frogs seasonal changes in liver intramitochondrial adenine nucleotides depend on the hormonal condition of animals. PMID- 1441802 TI - [The formation of interhemispheric asymmetry in human ontogeny during the perception of emotions in normal speech and in stuttering]. AB - Age peculiarities of functional brain asymmetry in perception of emotional information of speech have been revealed. It was shown that the age of 4-7 years is most important for formation of this asymmetry in emotional perception. It is in this age that functional reorganization of perception in stuttering children is observed. These data indicate that correction of emotional activity in stutterers should be made at early periods of their life. PMID- 1441803 TI - [The biological properties of Serratia marcescens bacteriophages]. AB - Sixteen phages active against bacteria of the genus Serratia have been divided into 4 groups on the basis of the study of their biological properties. As a result, 5 typing phages have been selected, which permitted the typing of 77.3% of S. marcescens cultures under study, divided into 13 phage types. PMID- 1441804 TI - [The resistance plasmid of Klebsiella pneumoniae that controls its cytotoxic activity]. AB - R-plasmid (40 MD) isolated from K. pneumoniae hospital strain makes Escherichia coli strain J62 capable of inducing a cytotoxic effect which can be detected in Hep-2 cell culture. In contrast to the initial E. coli strain J62 producing no changes in the monolayer, E. coli J62 cells containing P-plasmid induced pronounced cytotoxic changes and a sharp increase in the number of nonviable Hep 2 cells by hour 24 of interaction. PMID- 1441805 TI - [Lipopolysaccharide changes in smooth-type avirulent Shigella in comparison with initial virulent strains]. AB - The comparative study of the lipopolysaccharides (LPS) of virulent and avirulent strains of S. sonnei, phase I (smooth colonies), has been made. Electrophoresis of LPS and subsequent densitometry of electrophoregrams have revealed the increase of the fraction of long 0-chains with a considerable number of recurring elements in 2 out of 3 LPS preparations obtained from avirulent shigellae. In mice immunized with these LPS preparations a considerably greater number of antibody-producing cells can be detected in Jerne's test on sheep red blood cells (SRBC) sensitized with the LPS of a virulent strain than on those sensitized with the above LPS preparations. Long 0-specific chains supposedly inhibit the fixation of individual complement components on the corresponding sensitized SRBC. The LPS of the third avirulent strain of S. sonnei, phase I, with transposon integrated into its genome, which has led to the formation of the avirulent variant of a previously virulent strain, seems to contain fine structural differences from the initial virulent strain. The immunogenicity of the LPS of this avirulent strain is greatly (3-4 times) decreased, which is manifested by the number of antibody-producing cells detected in Jerne's test on SRBC sensitized with LPS preparations obtained from these two strains. PMID- 1441806 TI - [The development and study of the batch and multicyclic cultivation with a glucose feed of Neisseria meningitidis serogroup B]. PMID- 1441807 TI - [The migratory activity of HIV-infected people in the northwestern region and the routes of the possible spread of the infection]. AB - The epidemic situation in HIV infection in the northwestern region of this country has been analyzed. The ways of the spread of HIV infection among the infected persons, residents of the St. Petersburg region, Kaliningrad, Novgorod and Murmansk, have been studied. The infection is transmitted mainly through sexual contacts, both homosexual and heterosexual. High migration activity of HIV infected persons, homo- and heterosexuals, has been established, and a great number of unknown (casual) sexual contacts among them was noted. The results of these observations may be useful in the prognostication of the epidemic situation in HIV infection not only in the northwestern region, but also beyond its boundaries, and later in the optimization of screening. PMID- 1441808 TI - [Microbial ecology and a retrospective assessment of the possibility of predicting an outbreak of suppurative meningitis caused by a Serratia marcescens strain in a hospital for the nursing care of premature infants]. AB - An outbreak of purulent meningitides in a hospital ward for preterm babies, caused by Serratia marcescens strain of serovar 05/13 with multiple resistance, is described. Data on the results of the long-term observation of the ward showed that during three months preceding the outbreak the consecutive spread of the infective strain and its colonization of the intestine of children occurred. At the moment of the outbreak S. marcescens 05/13 was the dominating intestinal microflora in 37% of children in the ward and constituted 30% of the total aerobic flora in the intestine of the examined children. No S. marcescens strains were isolated from the feces and urine of the medical personnel and mothers. The importance of the observation of microflora colonizing newborn infants in the ward for the evaluation and prognostication of the epidemiological situation is discussed. PMID- 1441809 TI - [The definition of the forms of the epidemic process in intestinal infections]. AB - A method for the identification of the forms of the epidemic process in dysentery (annual, seasonal and outbreak forms) has been worked out. The method is based on the calculation of the upper limits of annual and seasonal morbidity from the data on the period of several years with the use of the formulae of binomial distribution, serving as the mathematical model of alternative random values, such as morbidity. The comparison of actual morbidity for each year of the analyzed period with the upper limits of annual and seasonal morbidity helps identify the form of the epidemic process. PMID- 1441810 TI - [An evaluation of the quality of tetanus anatoxins by gel electrophoresis]. AB - The study of tetanus toxoids obtained from different manufacturers in the USSR has shown that these preparations exhibit molecular heterogeneity. The method of gel filtration has made it possible to find out that tetanus toxoids from different manufacturers differ in the degree of their purification. The preparations produced by the manufacturing enterprises in Perm and Ufa have been found to contain considerably less ballast substances than the preparations produced in Moscow. PMID- 1441812 TI - [The antigenic activity of vaccines made from opportunistic microorganisms in an experiment to immunize animals by oral and combined methods]. AB - The results of the study of the antigenic activity of multicomponent vaccine consisting of staphylococcal, Klebsiella, Proteus, Escherichia coli antigens and staphylococcal monovaccine, introduced into rabbits and guinea pigs by different routes, are presented. As shown in this study, the multicomponent vaccine introduced orally in 5 administrations stimulated the production of antibodies to all components, but the intensity of antibody formation to each of them was different. Antibodies to E. coli antigen were found to be at the lowest level. Staphylococcal antigen, introduced orally both as the component of the multicomponent vaccine and as the monovaccine, ensured pronounced stimulation of the production of antistaphylococcal antibodies, not lower than that observed after subcutaneous injection. The comparative study of the activity of the multicomponent vaccine introduced by combined routes, oral-subcutaneous and subcutaneous-oral, showed the advantage of the former one. PMID- 1441811 TI - [Pseudomonads as parasites of protozoa]. AB - The experimental study of the interaction of Tetrahymena pyriformis with different microorganisms of the genus Pseudomonas, isolated from the soil, was made. The study revealed that T. pyriformis phagocytosed some Pseudomonas pigment forming species (P. cepacia, P. putida, P. fluorescens, P. pirkettii). The most pronounced cytopathogenic effect was produced by P. cepacia. The dynamic observations of the ultrastructural features of interaction between P. cepacia and protozoa were made. Even at early stages of this interaction some types of parasitiferous phagosomes containing both intact bacteria capable of multiplication by binary division and Pseudomonas cells exhibiting different degrees of destruction were registered. In several phagosomes morphologically intact bacteria differing in their cell-wall profiles and the density of their cytoplasm and nucleotide were present simultaneously. More dense cells with sinuous cell-wall membranes were more virulent. By hour 18 one giant parasitiferous vacuole was formed by fusion of smaller phagosomes, which subsequently broke up, liberating a new generation of bacteria. In infected cells disturbances in the structure of their mitochondria and macronucleus appeared. During the first 2 days of the joint cultivation of P. cepacia and T. pyriformis the accumulation of bacteria occurred due to the selection and multiplication of digestion-resistant bacterial cells, which ensured the resistance of this Pseudomonas population in association with protozoa. PMID- 1441813 TI - [An assessment of the immunoepidemiological efficacy of a liquid cultured killed vaccine against tick-borne encephalitis virus strain 205 in the Maritime Territory]. AB - Inactivated vaccine against tick-borne encephalitis (TBE), prepared on the basis of strain 205, is characterized by epidemiological (53%) and immunobiological activity. The appearance of a few TBE cases among the vaccinees is probably due to different maturation rate of immune response to various strains (different specificity of immune response). A suggestion has been made that no inactivated vaccine prepared from a single strain can produce a reliable protective effect because of pronounced heterogeneity of the population of TBE virus. PMID- 1441814 TI - [An evaluation of the scope of the circulation of Salmonella among the workers of commercial poultry- and meat-packing enterprises based on serological study data in the PHA test]. AB - Serum samples from 641 workers of large poultry and meat-packing plants were studied in the passive hemagglutination test with the use of Salmonella complex and serogroup diagnostica. A specific increase in the level of anti-Salmonella antibodies in 60.7% of poultry plant workers and in 9.8% of meat-packing plant workers was established. Among the workers of the poultry plants the most pronounced immune shifts were detected in persons having contacts with sick poultry and pathological material and among the employees of the meat-packing plant, in those who ate raw sausage meat. A high level of antibodies in the professional groups under study was observed as early as in the first year of work at the plant and persisted over the whole period of this work. Under the conditions of constant contamination of the workers of poultry and meat-packing plants with small doses of salmonellae specific immunity to this infection was seemingly induced, which inhibited the development of the manifest forms of infection, but did not prevent the formation of chronic carrier state. PMID- 1441815 TI - [The chemoluminescence of the primary focus of a suppurative infection and of isolated neutrophils exposed to dimephosphon]. AB - The influence of dimephosphone at concentrations of 0.001 M-0.75 M on the chemiluminescence of tissues at the focus of purulent infection in the ear of a guinea pig, on the survival rate of the experimental animals injected with the lethal dose of Staphylococcus aureus, as well as on the spontaneous and stimulated chemiluminescence of blood neutrophils in patients with wound infection, was studied. The study showed that different concentrations of dimephosphone oppositely influenced the intensity of the chemiluminescence of neutrophil suspensions and tissues at the focus of infection: low concentrations were found to produce stimulating action and high concentrations, suppressive action. At the highest concentration used in this study (0.75 M) dimephosphone prevented the death of the animals receiving lethal doses of S. aureus. PMID- 1441816 TI - [The characteristics of the polyclonal action and immunomodulating activity of bacterial peptidoglycans in oppositely reacting mouse strains]. AB - The data on the specific features of the polyclonal action of gram-negative bacteria on primary immune response to sheep red blood cells in oppositely reacting mouse strains are presented. Staphylococcus aureus and Bacterium flavum peptidoglycans have been found to increase the amount of antibody producing cells to thymus-dependent antigen only in the spleen of low-responsive mice. At the same time differences in the amino acid composition of these heteropolymers do not affect their stimulating activity. Differences between the capacity of B. flavum peptidoglycans to induce the activation of B cells in mice of different strains have been established. PMID- 1441817 TI - [The methods for correcting with specific and nonspecific immunomodulators the immunopathological processes arising from the administration of a staphylococcal vaccine]. AB - In mice immunized with staphylococcal vaccine the arresting of graft-versus-host reaction under the influence of small doses of staphylococcal vaccine, hyperimmune antistaphylococcal serum, cyclophosphamide, antilymphocytic serum has been demonstrated. Small doses of staphylococcal vaccine stimulated the production of antibodies to staphylococci and dermal extract in the animals, previously immunized with this vaccine, with the simultaneous suppression of cell mediated immune reactions to both antigens. Immunosuppressing agents have been found to inhibit humoral and cell-mediated immune response to microbial antigen and dermal extract. No influence of vermox and levamisole on the outcome of the graft-versus-host reaction has been registered; the latter preparation has been found to intensify cell-mediated immune reactions to microbial and tissue antigens. PMID- 1441819 TI - [The use of immunoenzyme analysis and immunoblotting for the serological characterization of mycobacterial antigens]. AB - The enzyme immunoassay and immunoblotting were used for the study of the serological activity of different mycobacterial antigens and the spectrum of antibodies to them in patients with different forms of tuberculosis and healthy persons. Antibodies in patients' sera were shown to bind antigens with different molecular weight. The level and spectrum of antibodies to purified protein fraction I made it possible to differentiate between patients with various forms of tuberculosis and healthy persons. PMID- 1441818 TI - [Interferon type I in protective body reactions in an experimental Klebsiella infection]. AB - The study on mice with experimental generalized Klebsiella infection, carried out with the use of microbiologic, immunologic and pathomorphologic methods, revealed that the intraperitoneal injection of type I interferon into the animals prevented their death and led to the rapid elimination of the infective agent from their body, enhanced the phagocytic and metabolic activity of polymorphonuclear lymphocytes of their peritoneal exudate, decreased the manifestation of microcirculatory and dystrophic changes in the parenchyma of their internal organs. PMID- 1441820 TI - [The 125th anniversary of the birth of the founder of Soviet epidemiology Daniil Kirillovich Zabolotnyi]. PMID- 1441821 TI - Protein-bound glycosaminoglycans in serum of patients with lung cancer and patients with diabetes mellitus. PMID- 1441822 TI - Competition between oleanolic acid glycosides in their transport to isolated vacuoles from Calendula officinalis leaf protoplasts. PMID- 1441823 TI - Induction of aberrant crypts in the colons of rats by alkylating agents. PMID- 1441824 TI - The effect of flavonoids on the mutagenic activity of aromatic amines. PMID- 1441825 TI - The effect of nitrofurazone and furazolidone on induction of cytochrome P-450 dependent monooxygenase system. PMID- 1441826 TI - The effect of exo- and endogenous compounds on the activity of glutathione-S transferase from monkey brain. PMID- 1441827 TI - Glutathione-S-transferase from boar testis: properties of the cytosolic and microsomal forms. PMID- 1441828 TI - Placenta as a protecting barrier--some properties of glutathione-S-transferase. PMID- 1441829 TI - Investigation of DNA structures with scanning tunneling microscope. PMID- 1441830 TI - Properties of phenol sulphotransferase from brain of the monkey Rhesus macaca. PMID- 1441831 TI - Collagenolytic activity in experimental atherosclerosis induced in rabbits fed a cholesterol-rich diet. PMID- 1441832 TI - Evaluation of metabolism of connective tissue proteins in patients with lung cancer. PMID- 1441833 TI - Effect of Cd2+ on phosphate exchange in Staphylococcus aureus. PMID- 1441835 TI - Protective action of cholesterol against changes in membrane fluidity induced by malathion. PMID- 1441834 TI - DNA-platinum-DNA cross-links formation induced by cis and trans diamminedichloroplatinum in isolated leukocyte nuclei. PMID- 1441836 TI - DNA-protein cross-linking induced by nitracrine in two strains of mouse lymphoma L5178Y cells. PMID- 1441837 TI - The influence of chosen physico-chemical factors on proteolytic activity of the hatching liquid of Coregonus albula and C. lavaretus. PMID- 1441838 TI - Blocking of the function of alpha-sarcin domain of 28S ribosomal RNA using the synthetic oligonucleotides as antisense DNA probes. PMID- 1441839 TI - Changes in thymocytes undergoing programmed death. PMID- 1441840 TI - Amino acid composition of human hair melanoproteins. PMID- 1441841 TI - Interaction of Fe3+, Cu2+ and Zn2+ with melanin and melanoproteins from bovine eyes. PMID- 1441842 TI - 59Fe distribution and elimination after melanin administration in mice. PMID- 1441843 TI - Effect of copper ions on hydrogenase activity of Desulfovibrio desulfuricans. PMID- 1441844 TI - Molecular basis for the functional diversity of enzyme forms of the LMW (Mr 38,000) acid phosphatase of the frog liver. AB - Recent studies on the structure and function of the tartrate-resistant acid phosphatase (Mr 38,000) of the frog liver are reviewed. The nature of the enzyme heterogeneity is elucidated on a molecular and physiological basis. The following structure-activity relationship is proposed: the enzyme protein is modified by glycosylation processes leading to formation of the different enzyme forms. The oligosaccharide chain stabilizes the final structure of the enzyme forms with altered conformation causing different exposure of the essential functional groups (e.g. sulfhydryl residues, antigen determinants). This leads to different physiological events necessary for fulfillment of metabolic requirements of the cell. PMID- 1441845 TI - Exopolysaccharides of Rhizobium leguminosarum biovar trifolii harbouring cloned exo region. AB - Rhizobium leguminosarum bv. trifolii produces an acidic exopolysaccharide (EPS) which plays an important role in the development of nitrogen-fixing nodules. Tn5 mutant of R. trifolii 93 defective in EPS production (Exo-) forms ineffective (Fix-) nodules on red clover. This Exo- mutation is complemented by the pARF1368 and pARF25 cosmids isolated from gene bank of Rhizobium trifolii TA1, but the complementation is not correlated with restoration of Fix+ phenotype. Furthermore, these cosmids introduced to wild-type of R. trifolii 24 repress its ability to form nitrogen-fixing nodules. These results might suggest that bacteria with cosmids carrying the exo region form EPS of altered structure. It has been shown by 1H-n.m.r. that exopolysaccharides produced by R. trifolii 93pARF-1368 and 93pARF25 contain less non-carbohydrate residues (acetyl, pyruvyl and 3-hydroxybutanoyl) than the wild type EPS. These data suggest that the biological activity of the exopolysaccharide of R. trifolii depends on the contents of the non-carbohydrate substitutions. PMID- 1441846 TI - Adenosine deaminase: physical and chemical properties of partially purified mitochondrial and cytosol enzyme from rat liver. AB - Adenosine deaminase (ADA) was partially purified 486- and 994-fold from rat liver mitochondria and cytosol, respectively. Relative molecular mass of the enzymes from both fractions was 34,000. Km for adenosine and 2'-deoxy-adenosine were 3.08 x 10(-5) M and 3.03 x 10(-5) M for mitochondrial ADA and 3.12 x 10(-5) M and 2.87 x 10(-5) M for cytosolic ADA. The enzyme from both subcellular fractions had the maximum activity at pH 7.5-8.0, and pI 5.2 and 4.2 for mitochondrial and cytosolic enzyme, respectively. The enzyme was inhibited by erythro-9-(2-hydroxy 3-nonyl)adenine and 2'-deoxycoformycin with Ki 4.4 x 10(-7) M and 3.2 x 10(-7) M for mitochondrial ADA and 4.9 x 10(-7) M 2.8 x 10(-7) M for cytosolic ADA. Among the natural nucleoside and deoxynucleotide derivatives tested, deoxy-GTP and UTP inhibited only cytosolic adenosine deaminase by 60% and 40%, respectively. PMID- 1441848 TI - Uptake and subcellular distribution of intraventricularly injected [1-3H]dolichol in rat brain. AB - The uptake of C95[1-3H]dolichol in the form of liposomes into rat brain after the intracerebral and intraperitoneal injection was investigated. Efficient, time dependent uptake of dolichol into the brain was observed exclusively after the intraventricular injection. Within 24 h after the injection about 10% of the applied dolichol was found in the brain and 1.5% in liver. The distribution of dolichol in various parts of rat brain decreased in the order: cerebellum greater than midbrain greater than grey matter and brain stem greater than white matter. Seven days after the injection total radioactivity in the brain decreased and concomitantly a significant increase was observed in blood circulating and liver of the rat. The highest activity was found in grey matter and it remained a few times higher in comparison with that in white matter. About 80% of the dolichol taken up by the brain membrane was recovered in the following subcellular fractions: crude nuclear fraction greater than microsomes greater than mitochondria greater than synaptosomes greater than myelin. These results demonstrate for the first time that dolichol is actively taken up by the brain membrane exclusively after intraventricular injection of dolichol phosphatidylcholine in the form of liposomes; this method may be useful in studies on the role of dolichol in brain function. PMID- 1441847 TI - The 45 kDa and 27 kDa yeast's protein kinases are not immunologically related. AB - Two yeast casein kinase type-1 species of 45 kDa and 27 kDa (CK1) were purified to apparent homogeneity and used for investigation of their immunological affinity. Antisera against the two kinases were isolated; the antibody against the 45 kDa kinase did not react with the 27 kDa enzyme. The 27 kDa casein kinase was recognized only by its own antibody. The obtained data strongly suggest that the low molecular mass CK-1 is not a proteolytic product of the 45 kDa kinase species. PMID- 1441849 TI - Rapid separation of tyrosine-specific tRNA from white lupin. AB - During isolation of total ribonucleic acids from white lupin (Lupinus albus) and their subsequent separation by 10% polyacrylamide gel electrophoresis, a fast migrating RNA band is very well separated. The nucleotide sequence analysis of 76 nucleotide long sequence with many modified nucleosides was found to be identical with that of tyrosine specific tRNA of yellow lupin seeds (Lupinus luteus) and wheat germ (Triticum aestivum). Also this tRNA(Tyr) is identical with plant amber suppressor tRNA. The presented approach offers a very rapid method of purification of plant tRNA with UAG suppressor activity. PMID- 1441850 TI - Identification of ectopic ventricular foci by means of intracavitary potential mapping: a proposed method. PMID- 1441851 TI - Quantitative analysis of ventricular late potentials (LP) in healthy subjects. Comparative study with Holter monitoring. AB - Signal averaging is a technique that improves the signal-to-noise ratio. It allows the detection of low-amplitude wave formes in the terminal portion of the QRS complex, also known as ventricular late potentials. A high incidence of arrhythmic events is found in patients with abnormal ventricular late potentials after an acute myocardial infarction. Few wide studies have been conducted in healthy subjects to assess normal values. One hundred sixty-five healthy subjects are enrolled in our study (59 men and 106 women). The results (mean +/- standard deviation) are as follows: duration of filtered QRS: 89.5 +/- 9.1 ms; duration of the low-amplitude signals in the terminal portion of QRS < 40 microV: 27.1 +/- 7.8 ms; root-mean-square voltage in the last 40 ms: 47.2 +/- 29.5 microV. A signal difference is noted between men and women for the QRS duration. No difference is found in HFD40 and RMS40. QRS duration confidence limits of 95% are < 108 ms for the total group. HFD40 and RMS40 confidence limits of 95% are respectively of 43 ms and 13 microV. There is no significant difference of the values for age. There is no relation between the severity of a ventricular arrhythmia and the values of the three parameters of the late potentials in a healthy subjects population. PMID- 1441852 TI - Defibrase, a purified fibrinolytic protease from snake venom in acute myocardial infarction. AB - To investigate the thrombolytic effects of defibrase in AMI, 157 pts with AMI were studied. Of the 157 pts, 87 were assigned to defibrase thrombolysis and 70 to the conventional therapy plus heparin (control). Coronary arteriography was performed in 36 pts of the defibrase group and 26 of the control group. Pretreatment coronary arteriography was performed in 10 pts and total occlusion of infarct-related artery (IRA) was demonstrated in 7. Thirty to 45 min after either intracoronary or intravenous defibrase thrombolysis, recanalization occurred in 4 of the 7 pts. The perfusion and stenosis was improved in 2 of the 3 pts with patent IRA. Of the 10 pts who underwent emergency coronary arteriography after the onset of i.v. defibrase thrombolysis, 6 were shown to have patent IRAs. Of the 16 pts who underwent coronary arteriography two weeks after the i.v. defibrase thrombolysis, 13 were shown to have patent IRAs. In contrast, only 11 of the 26 pts in the control group had patent IRAs two weeks after admission to the hospital. Of the 36 angiographic cases of the defibrase group, 15 underwent follow-up coronary arteriography, only 1 pt showed reocclusion. In comparison to the control group, the pts in the defibrase group had earlier CPK peaking, higher percentage of pts with LVEF > 0.5, a lower mortality and complication rate. Major spontaneous bleeding complications were rarely seen with defibrase. The results indicate that defibrase is an effective thrombolytic agent with a reasonable recanalization rate, low reocclusion rate and a low rate of bleeding complications. PMID- 1441853 TI - Does the measurement of left ventricular isovolumic relaxation time allow early prediction of cardiac allograft rejection? AB - In order to evaluate the value of isovolumic relaxation time measurement for the diagnosis of moderate acute rejection episodes in cardiac allograft recipients a comparison was made with the histological results from the endomyocardial biopsy. A total of 202 isovolumic relaxation time measurements from 26 patients were compared to the biopsy results. The technique used to record isovolumic relaxation time was dual M-mode echocardiography. In addition a combined phonoechocardiography was used for 54 isovolumic relaxation time measurements from 17 patients. A good correlation was found between these two methods. When the biopsy results were normal the isovolumic relaxation time was 71.4 +/- 15.1 ms. When moderate acute rejection episodes were present isovolumic relaxation time decreased to 50.2 +/- 21.2 ms (p < 0.001). In spite of the close correlation detected at group level, there was a large variability of the measurements without accompanying changes in the biopsy specimen. At the same time a significant overlap was found between the measurements taken during rejection and non-rejection periods making it impossible to use these methods for clinical decision making. We conclude that isovolumic relaxation time measured with these methods is not a sufficiently sensitive parameter for the diagnosis of moderate acute rejection episodes in the individual patient, and in our experience, it is not a substitute for endomyocardial biopsy and can not be applied for clinical decision making. PMID- 1441854 TI - A comparison of cardioversion of atrial fibrillation using oral amiodarone, intravenous amiodarone and DC cardioversion. AB - Fifty-two consecutive patients with atrial fibrillation underwent 86 episodes of attempted cardioversion with oral amiodarone, intravenous amiodarone or DC cardioversion. The presence of chronic obstructive pulmonary disease or a presenting heart rate of less than 110 beats per minute were associated with a favourable outcome. Conversion to sinus rhythm was achieved in 29% of the group treated with oral amiodarone, 42% of the group treated with DC cardioversion and 64% of the group given intravenous amiodarone. The overall statistical significance of this distribution on chi square testing was p < 0.032. However when only first attempts at cardioversion were analyzed there was no difference between intravenous amiodarone and DC cardioversion. PMID- 1441855 TI - Target organ status and cardiovascular risk in borderline hypertension. AB - In order to assess the prevalence of target organ damage 78 men with borderline hypertension, according to the World Health Organization criteria, and 67 normotensive controls underwent echocardiographic, electrocardiographic and fundoscopic examination, followed by ambulatory blood pressure monitoring for 24 hours. Echocardiographic left ventricular hypertrophy was found in 13 borderline hypertensive subjects (16.6%), while no electrocardiographic or fundoscopic abnormalities could be detected. Our data suggest that noninvasive assessment of cardiovascular status, including echocardiography, allows recognition of a subset of borderline subjects with an increased risk for subsequent cardiac morbid events, thereby improving prognostic stratification. PMID- 1441856 TI - Surgery for massive pulmonary embolism. AB - Pulmonary embolectomies were performed in 30 patients from January 1973 until December 1991 in the University Hospital of Leuven. There was an 80% hospital survival. The late follow-up showed no recurrent pulmonary emboli. The preoperative haemodynamic status was the most important predictor for survival. Patients, under cardiopulmonary resuscitation or in profound cardiogenic shock before surgery, had a survival of only 50% while all other patients survived. Angiography, performed in only 23% of the cases, remained the most important diagnostic tool until the advent of transthoracic and transoesophageal echocardiography. Thrombolysis is an acceptable alternative in the stable patient, but pulmonary embolectomy is life-saving in the haemodynamically unstable patient and when thrombolysis is contraindicated. PMID- 1441857 TI - Early venous coronary bypass graft occlusion in a patient with non-specific aortitis: a case report. AB - A 58-year-old woman with aortic valve regurgitation and bilateral ostial coronary artery stenosis due to non-specific aortitis is presented. Four months after aortic valve surgery and venous bypass surgery, orificial occlusion or high grade stenosis of the bypass grafts occurred. Repeat coronary arteriography was followed by cardiac arrest and emergency surgery but patient did not survive. The etiology, pathological findings and surgical approach are discussed. PMID- 1441858 TI - Thrombolytic therapy and acute aortic dissection. AB - Thrombolytic (tissue plasminogen activator) and antithrombotic treatment (heparin and aspirin) were given to a 47-year-old man with an acute type II aortic dissection presenting as an acute anterior myocardial infarction. During treatment he developed cardiac tamponade and an ischaemic stroke. Transoesophageal echocardiography (but not computed tomographies of the chest) revealed the correct diagnosis. After surgical repair (Bentall procedure) there was a complete recovery. PMID- 1441859 TI - The nursing care recording system. A preliminary study of a system for assessment of nursing care demands in the ICU. AB - A new system, Nursing Care Recording (NCR), for the recording of nursing care in a general ICU is presented. NCR classifies ICU patients according to their need for intensive nursing care. Comparing the NCR with the Therapeutic Intervention Scoring System (TISS), a correlation coefficient of 0.60 was found. The main difference between the two systems was related to recording procedures allowing changes in nursing intensity within a 24-h period, reflecting patient improvement due to therapy, which was detected by NCR but not by TISS. NCR can be used to estimate nursing capacity during different shifts and may be useful in the assessment of the total nursing staff necessary for a given ICU. It is suggested that NCR will allow detection of changes in the nursing care work load, whether this change is due to new activities in the unit or to alterations in the individual patient care. PMID- 1441860 TI - Influence of the type of anaesthesia on post-operative subjective physical well being and mental function in elderly patients. AB - Standardized behavioural observations were used to establish the influence of the type of anaesthesia on the mental function and the subjective physical well-being in 60 patients, all men, following urological surgery. The patients were randomized to two groups, receiving spinal or general anaesthesia. For evaluation of the influence of pre-operative physical condition on post-operative mental function, a supplementary group of 34 patients with pre-existing cardiovascular and/or pulmonary disorders was included in the study. These patients all received spinal anaesthesia. The patients were observed from the day before surgery until 4 weeks after. In all patients a short-lasting temporary decline in mental function was observed. The outcome was not influenced by the type of anaesthesia. In the two groups receiving spinal anaesthesia the decline in post-operative mental function and subjective sense of well-being was most pronounced in patients with a compromised physical condition pre-operatively. Four weeks after surgery, no signs of mental deterioration were present; however, the subjective sense of physical well-being had not fully returned. PMID- 1441862 TI - Is acupuncture an alternative in idiopathic pain disorder? AB - This study investigated the pain-relieving effect of an intensive type of periosteal acupuncture stimulation in patients with idiopathic pain disorder. Twelve patients, 2 males and 10 females, with a mean age of 54, were included in the study. The average duration of their pain was 12.6 years. Each treatment consisted of brief but painful manual stimulation of 3 to 4 periosteal sites. Over a 3-8-month period each patient had between 4-11 treatments, an average of 7. Analgesic drugs that patients were on prior to the study were continued but no other physical or psychological treatment for their pain was applied. Ten patients had either no responses to treatment or only transient responses which were not maintained until the following treatment. Two patients benefitted from treatment, having long periods of substantial pain reduction. All responses were assessed on pain scales maintained daily before and during the entire period of treatments. For the majority (83%) of patients in this study, with an idiopathic pain disorder, periosteal acupuncture stimulation was not a treatment alternative. PMID- 1441861 TI - Anaesthetic uptake and washout characteristics of patient circuit tubing with special regard to current decontamination techniques. AB - The amounts of halothane and isoflurane trapped after exposure for up to 3 h at 2 MAC in commonly used anaesthesia circuit tubing were quantitated by gas chromatography. The decontaminating effects of procedures such as flushing with oxygen, thermal disinfection and/or routine storage were assessed in a similar way. After halothane exposure, anaesthetic content was highest in silicone (398 +/- 55 mg 100 g-1). Lower quantities were found in all other tubings investigated (electrically conductive latex: 64 +/- 4, conductive rubber: 62 +/- 4, polyethylene-vinyl-acetate (PEVA): 293 +/- 10 and 149 +/- 17 for non-conductive corrugated and spiral tubes, respectively, polysulfone (Hytrel): 155 +/- 10 mg 100 g-1). The isoflurane contents were substantially lower (silicone: 278 +/- 23; others: 55 +/- 7, 61 +/- 6, 163 +/- 9 and 86 +/- 8, 74 +/- 4 mg 100 g-1). The tubings' content did not correlate with the material's partition coefficient as full saturation was not achieved during exposure. Decontamination procedures reduced the content of volatile anaesthetics to a variable extent. Conductive latex and rubber showed the highest residual content, even after thermal disinfection and subsequent storage. Twenty-minute flushing with oxygen (8 l min 1) decreased effluent gas concentrations below 5 p.p.m. in all tubings. With silicone, after 1 h flushing, halothane concentrations still exceeded 10 p.p.m. (isoflurane: 8 p.p.m.). It is concluded that urgent decontamination by a 20-min flush warrants the safe re-use of previously 'contaminated' conductive rubber and latex as well as polysulfone tubings in critical situations, e.g. in malignant hyperthermia patients if disposable tubing is not immediately available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441864 TI - Effect of piroxicam in addition to continuous thoracic epidural bupivacaine and morphine on postoperative pain and lung function after thoracotomy. AB - Twenty-eight patients scheduled for lung resection with lateral thoracotomy and postoperative chest drains during combined thoracic epidural bupivacaine plus morphine and general anaesthesia were studied. Postoperative pain treatment was continuous epidural infusion of bupivacaine 0.25% 5 ml h-1 plus morphine 0.2 mg h 1 for 48 h and, in addition, the patients received rectal piroxicam 40 mg randomly and double-blind 12 h and 1 h before surgery and 20 mg 24 h-1 postoperatively or placebo. Pain was evaluated at rest, during cough and mobilisation, together with pulmonary function (FEV1, FVC, PEFR) and sensory level of analgesia repeatedly for 48 h. The results showed efficient pain relief, but without differences in pain scores or need for supplementary analgesics between the two groups. Pulmonary function decreased similarly in the two groups. Thus we were unable to show enhanced analgesia by supplementing an otherwise effective low-dose epidural bupivacaine and morphine treatment with piroxicam after thoracic surgery with chest drains. PMID- 1441863 TI - Intra-articular bupivacaine plus adrenaline for arthroscopic surgery of the knee. AB - The purpose of the study was to evaluate three different doses of intra-articular bupivacaine plus adrenaline in relation to per- and postoperative pain relief following arthroscopy. Sixty patients were allocated to three groups of 20 patients each scheduled for arthroscopy. They were randomized prospectively to receive bupivacaine plus adrenaline 25 mg + 50 micrograms, 50 mg + 100 micrograms, 75 mg + 150 micrograms, respectively, diluted to a volume of 30 ml. Four patients were excluded because the operation could not be carried out under intra-articular analgesia, 18 patients had a diagnostic arthroscopy and 38 patients had different arthroscopic operations performed. The number of patients scoring pain in the knee as moderate or severe was less in Group 3 than in the other two groups, i.e. the highest dose had a better pain relief. No adverse effects were registered. With respect to per- or postoperative administration of analgesics, postoperative pain occurrence, and the surgeon's acceptance of the method, there were no statistically significant differences. Ninety-two percent of the patients would prefer intraarticular analgesia if they should need to have another arthroscopy performed. PMID- 1441865 TI - Pulmonary granulocyte accumulation is reduced by nebulized corticosteroid in septic pigs. AB - Nebulized beclomethasone dipropionate was administered to 14 anesthetized and artificially ventilated pigs at 6-hourly intervals after infusion of live S. aureus (BDP group). Changes in pulmonary activity from autologous granulocytes labeled with In-111 was detected externally for 12 (n = 8) to 44 h (n = 6). The changes were compared with those in ten pigs (12 h n = 7, 44 h n = 3) subjected to the same insults but given no corticosteroid (placebo group). Serial measurements of blood radioactivity, and cardiac output were performed in animals observed for 12 h. Corticosteroid-treated pigs showed a gradual decline in decay corrected pulmonary In-111 activity. The placebo group displayed a more varied reaction, but most animals had an increased activity compared to the corticosteroid group. The difference between the groups was significant at 8 h (BDP-group 92% (88-98), placebo-group 107% (97-121), median (lower-upper quartiles), baseline = 100%. P < 0.01, U-test). Blood radioactivity and cardiac output did not differ significantly between the two groups. Nebulized corticosteroid thus diminished pulmonary granulocyte accumulation, which may be of value in the treatment of septic respiratory distress. PMID- 1441866 TI - Ten ml bupivacaine 0.125% with 12.5 micrograms epinephrine is a reliable epidural test dose to detect inadvertent intravascular injection in obstetric patients. A double-blind study. AB - A double-blind study was designed in order to determine the specificity and sensitivity of an epidural test dose to detect inadvertent intravenous injection in obstetric patients undergoing epidural analgesia. Forty unselected obstetric patients were given an intravenous injection of 10 ml bupivacaine 0.125% with 12.5 micrograms epinephrine (test dose) or 10 ml normal physiologic saline. The maternal heart rate was monitored by the direct ECG mode of a fetal monitor and registered simultaneously with the tocogram. The primary investigator was blinded to the solution he injected into an antecubital vein. After the injection was given, he recorded his judgment of which solution he had administered. Eight other anesthesiologists made similar judgments on the basis of the recordings plus various levels of additional information (presence or absence of epidural analgesia, time of injection, subjective signs and symptoms). In contrast to the primary investigator, the blood pressure values were not given to them. For the primary investigator, the specificity of the test dose was 100% and the sensitivity 97.5%. The judgments of the 8 other anesthesiologists resulted in an excellent specificity (99.1%) and a good sensitivity (91.9% with information on time of injection and subjective signs and symptoms). The better performance of the primary investigator is probably due to the availability of blood pressure data. PMID- 1441867 TI - Thiopentone or propofol for induction of isoflurane-based anaesthesia for ambulatory surgery? AB - This study compares psychomotor recovery following induction of anaesthesia with either thiopentone or propofol in 30 healthy, unpremedicated patients undergoing outpatient arthroscopic procedures of the knee. A battery of tests including simple reaction time (SRT), choice reaction time (CRT), perceptive accuracy test (PAT) and digit symbol substitution test (DSST) were done before anaesthesia. The patients were randomly divided into two groups: Group 1 was induced with thiopentone 5-6 mg/kg while Group 2 was induced with propofol 2-3 mg/kg. Anaesthesia was then maintained with isoflurane (0.5-2%) in oxygen and air, and supplements of alfentanil were given for analgesia during spontaneous respiration with a face mask. Psychomotor recovery assessed every 30 min postoperatively for 120 min showed that patients in Group 1 had not returned to baseline values until 120 min after the operation on the PAT, while those in Group 2 had returned to baseline values at 60 min. No patient had any significant side effects. The SRT, CRT and DSST proved to be relatively insensitive in the detection of residual effects of anaesthesia and had a significant learning effect. This study suggests that induction of anaesthesia with propofol followed by maintenance with isoflurane in oxygen and air during spontaneous ventilation is associated with rapid psychomotor recovery and is a suitable method for ambulatory surgery. The PAT is sensitive and not associated with some of the problems found with other commonly used tests. PMID- 1441868 TI - Effects of verapamil on histamine-induced changes in lung mechanics. AB - The effects of verapamil on airway resistance and total thoracic compliance were studied in 15 rabbits with histamine-induced changes in lung mechanics. The animals, after being tracheotomized under anaesthesia, were subjected to mechanical ventilation in a time-cycled, volume-limited mode. Airway pressure and gas flow signals measured by a pneumotachograph and integrated for volume, were registered on a recorder. Each animal was given histamine hydrochloride in an isotonic solution of sodium chloride at a rate of 0.05 micrograms.kg-1.min-1 through a peripheral venous line. Verapamil was infused intravenously in an isotonic solution of sodium chloride at a rate of 20 micrograms.kg-1.min-1 after the initiation of histamine. Verapamil reduced the histamine-induced increase in airway resistance by 20% at 20 min after the start of administration. PMID- 1441869 TI - Haemodynamic changes associated with thermodilution cardiac output determination during myocardial ischaemia or pulmonary oedema in dogs. AB - Since the technique of thermodilution (TD) cardiac output measurements per se causes haemodynamic alterations, the authors examined whether the alterations elicited by iced injectate are augmented in the presence of myocardial ischaemia (MI) or pulmonary oedema (PE), compromised conditions frequently associated with critically ill patients. MI (N = 7) or PE (N = 7) was induced by clamping the anterior descending coronary artery or by a slow infusion of oleic acid into the right atrium, respectively, in anaesthetized dogs. Injection of iced injectate, 3 ml, caused similar changes in heart rate, mean systemic and pulmonary arterial pressures, pulmonary blood flow, right ventricular dP/dt, and right atrial pressure in dogs with and without MI or PE. Cardiac output estimated by TD correlated closely with pulmonary blood flow measured by electromagnetic flowmeter in both MI and PE (r > 0.9). No profound alterations in haemodynamics were observed at any injection during TD cardiac output measurements under MI or PE. These results indicate that TD cardiac output determination does not cause serious haemodynamic alterations, and can estimate right ventricular output accurately under MI and PE. PMID- 1441870 TI - Effects of epinephrine and clonidine on plasma concentrations of spinal bupivacaine. AB - ASA II-III patients, scheduled for peripheral vascular surgery, were included in a study designed to assess the effect of spinal epinephrine and clonidine on plasma concentrations of spinally administered 0.5% glucose-free bupivacaine. Patients were allocated randomly to three groups to receive via a spinal catheter 22.5 mg (4.5 ml) of bupivacaine alone (Group B, 9 patients) or combined with 0.3 mg epinephrine (Group BE, 10 patients) or 0.15 mg clonidine (Group BC, 10 patients). Sensory blockade was assessed by pin-prick and motor blockade on the Bromage scale. Bupivacaine plasma concentrations were measured by gas chromatography. A trend to prolongation of local anaesthetic blockade was documented in patients receiving bupivacaine plus epinephrine or clonidine. (Time to regression of sensory blockade to L2: 170 +/- 75 min in Group B, 230 +/- 50 min in Group BE, 232 +/- 64 min in Group BC.) The maximum peak concentration (Cmax), the time to reach Cmax (Tmax) and the time-concentration curve from 0-180 min (AUC) were not different for the three groups (Cmax 228 +/- 112 ng.ml-1 in Group B, 215 +/- 103 ng.ml-1 in Group BE, 234 +/- 159 ng.ml-1 in Group BC; Tmax 41 +/- 34 min in Group B, 59 +/- 31 min in Group BE, 68 +/- 32 min in Group BC; AUC 31.0 +/- 1.7 mg.ml-1.min-1 in Group B, 27.3 +/- 1.1 mg.ml-1.min-1 in Group BE, 27.0 +/- 1.1 mg.ml-1.min-1 in Group BC). The results of this study suggest that epinephrine and clonidine do not decrease blood resorption of spinal bupivacaine. PMID- 1441871 TI - Plasma prilocaine and mepivacaine concentrations after combined lumbosacral plexus block. AB - In a pharmacokinetic study of combined sciatic/3-in-1 block for lower limb surgery, the two moderate-acting local anaesthetics prilocaine and mepivacaine were compared. The mean maximum venous plasma concentrations of mepivacaine were more than twice as high as when prilocaine was used as anaesthetic (5.1 micrograms/ml vs. 2.37 micrograms/ml). When used in combination with the former, ornipressin did not reduce plasma concentrations of mepivacaine to values which were below the threshold for toxic symptoms (5-6 mg/ml). The peak plasma concentrations exceeded the threshold of 5 micrograms/ml in four of the nine patients of the mepivacaine group (maximum value 7.21 mg/ml) and in two of the nine patients of the mepivacaine+ornipressin group (maximum value 8.61 micrograms/ml). PMID- 1441873 TI - A two-dose epidural morphine regimen for cesarean section patients: therapeutic efficacy. AB - A single dose of epidural morphine (EM) usually produces 24 h of post-cesarean section (CS) analgesia and patients require supplemental analgesics beyond this period. This study assesses if a second dose of EM administered 24 h after the first one offers superior therapeutic efficacy compared to conventional analgesics. Patients (n = 100) were randomized to receive one or two doses of epidural morphine. In all patients, EM 5 mg was administered after delivery. After 24 h patients received epidurally either normal saline (n = 50, Group 1) or morphine 5 mg (n = 50, Group 2). An independent observer used a visual analogue scale to assess nausea, itching, and analgesia 24 h after each injection. Results were expressed as mean +/- 1 s.e. mean and analyzed using nonparametric methods. The second dose of EM produced a significantly lower incidence and severity of nausea and itching than did the first dose (P < 0.01) in Group 2 with no difference in analgesia. The second day postoperative pain score in Group 1 was significantly greater than the first day score in the same group, and significantly greater than the severity score in Group 2. Only 36% of patients receiving two doses of EM required supplemental analgesics beyond 48 h compared to 76% of those receiving one dose (P < 0.01). No serious complications were noted. In summary, the use of a second dose of EM for post-CS analgesia produces better analgesia and reduces the need for oral analgesics. The second dose produced fewer side-effects, probably due to acute tolerance to morphine. PMID- 1441872 TI - Prilocaine in lumbosacral plexus block--general efficacy and comparison of nerve stimulation amplitude. AB - The significance of the threshold amperage of peripheral nerve stimulation (PNS) for the efficacy and latency of sciatic block is shown in a controlled randomized study of stimulation amplitude. In all cases the block was complete within a short time when the threshold amperage was 0.3 mA or less. Incomplete motor and sensory blocks occurred with higher stimulation amplitudes of 0.5 and 1.0 mA. In view of these results a prospective study of the clinical efficacy of 852 combined sciatic/3-in-1 blocks using prilocaine, and performed by means of peripheral nerve stimulation was carried out. No CNS or cardiovascular complications, no problems resulting from methaemoglobinaemia and, above all, no nervous lesions were observed. The limiting factor for surgery of the lower limb with this method of anaesthesia is the tolerance of the femoral tourniquet which depends mainly on the efficacy of the 3-in-1 block. Ninety-one per cent of the combined blockades were primarily successful when there was no tourniquet at all, and 87% when the tourniquet was placed on the lower leg. In the course of surgery with a femoral pneumatic tourniquet, only 55% of the blocks did not require supplement when 20 ml of 1% prilocaine was used for the 3-in-1 block, while 72% and 74% were efficacious with 30 ml and 35 ml, respectively. The efficacy of the sciatic block proved to be extremely high (> 95%), its success depending on the dosage of the local anaesthetic and correct execution of the peripheral nerve stimulation. PMID- 1441875 TI - Failure of anaesthesia after accidental subdural catheter placement. AB - A case is described where an epidural anaesthetic was complicated by dural puncture, following which attempted conversion to a continuous subarachnoid infusion technique resulted in failure of anaesthesia. Accidental subdural catheter placement was confirmed radiologically, subdural spread of solution being demonstrated; however, only minimal anaesthetic effects were produced. PMID- 1441874 TI - Influence of plasma cholinesterase activity on recovery from mivacurium-induced neuromuscular blockade in phenotypically normal patients. AB - The significance of plasma cholinesterase (pChe) activity for the duration of action of mivacurium in phenotypically normal patients was evaluated in 35 patients during neurolept anaesthesia. The response to train-of-four nerve stimulation was recorded using a Myograph 2000. Ten patients with normal pChe (Group I) and five patients with decreased pChe activity (Group 2) were given a small test dose of mivacurium 0.03 mg kg-1. Mivacurium 0.1 mg kg-1 was administered following spontaneous recovery from the first dose. The mean suppression of the height of the first (T1) of the train-of-four responses following mivacurium 0.03 mg kg-1 patients with normal and decreased enzyme activity was 40% and 56%, respectively, and the mean T1 suppression after mivacurium 0.1 mg kg-1 was 100% in both groups. The times to different levels of twitch height recovery following the 0.1 mg kg-1 dose did not differ between the two groups of patients. Another 20 patients with normal or decreased pChe activity (Group 3) were given mivacurium 0.2 mg kg-1. In this group the time to maximum block was 1.4 min (1.0-4.0) mean (range) and the time to reappearance of the T1 response was 15.0 min (7.4-22.7) (range). An inverse relationship was found between the patients' pChe activity and the time to first response. It is concluded that mivacurium is short-acting in patients with normal pChe phenotype and normal to low-normal pChe activity. No patient with very low pChe activity was included in the study. A prolonged response to mivacurium may, however, be expected in these patients. PMID- 1441876 TI - Comparison of ketorolac and morphine for postoperative pain after major surgery. AB - This study was designed to determine the relative analgesic efficacy and safety of single intramuscular injections of ketorolac (10 mg or 30 mg) and morphine (10 mg) in patients of either sex with moderate to severe pain after major surgery. In a single-dose, randomised, double-blind study of parallel design, pain was assessed immediately before injection of test medication and at regular intervals for 8 h thereafter. One hundred and seventeen patients (109 undergoing cardiac surgery; 8 lung surgery) were randomized to one of the three treatment groups. Pain intensity was assessed using a 5-point verbal scale before administration of study drugs. Postadministration, at 30 min and hourly for 8 h, pain intensity and pain relief were assessed, again using the 5-point verbal scale. Additionally, as a measure of analgesia, forced expiratory volume (FEV1) was obtained in all patients. Vital signs including blood pressure, pulse, temperature, respiratory rate and blood gases (PaCO2) were recorded prior to and after study medication. Based on hourly pain intensity differences and hourly pain relief observations, ketorolac 10 mg was generally more effective than morphine 10 mg, and ketorolac 30 mg was generally more effective than ketorolac 10 mg. The results of this study show that ketorolac is an effective and safe (with regard to arterial pressure, blood gases and lung function) analgesic for relief of postoperative pain after major surgery in stable patients. No clinically significant adverse effects occurred during the study. One cannot exclude an influence on patients with organ system dysfunction or on parameters not measured in this study. PMID- 1441877 TI - Lidocaine hydrocarbonate and lidocaine hydrochloride for cesarean section: transplacental passage and neonatal effects. AB - Twenty-six patients, ASA physical status 1, scheduled for elective cesarean section, were divided at random into two groups and received via an epidural catheter 20 ml of 2.2% lidocaine hydrocarbonate (17.3 mg.ml-1 lidocaine base) with 5 micrograms.ml-1 epinephrine freshly added (Group CO2 = 13 patients) or 20 ml of 2% lidocaine hydrochloride (17.3 mg.ml-1 lidocaine base) also with 5 micrograms.ml-1 epinephrine freshly added. Following clampage of the umbilical cord (at 40.1 +/- 4.9 min after the injection of lidocaine for the CO2 group and at 41.0 +/- 5.4 min for the HCl group), serum concentrations of lidocaine were measured both in the mother and in the umbilical vein. All newborns were examined by the same blinded pediatrician with Apgar scores at 1, 5 and 10 min and with Neurobehavioral Adaptive Capacity Scores (NACS) at 15 min, 2 h and 24 h. The concentrations of lidocaine in the serum were comparable in both groups: in the mothers 8.61 +/- 1.48 mumol.l-1 for the CO2 group vs 8.04 +/- 2.36 mumol.l-1 for the HCl group and in the newborns 3.86 +/- 0.84 mumol.l-1 for the CO2 group vs 3.92 +/- 0.95 mumol.l-1 for the HCl group. The ratio of umbilical vein to maternal vein concentrations of lidocaine was also similar in both groups: 0.45 +/- 0.07 for the CO2 group vs 0.54 +/- 0.24 for the HCl group. The percentage of newborns with a normal NACS (score > or = 35/40) was equal in both groups, i.e. 91% at 15 min and 2 h of life and 100% at 24 h of life.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441878 TI - Onset and duration of hypoalgesia of lidocaine spray applied to oral mucosa--a dose response study. AB - Lidocaine is often used as a topical analgesic prior to painful procedures performed in the oral cavity and upper airways. In this study the optimal time interval for performance of painful procedures in the oral cavity and the upper airways was determined by spraying lidocaine solution on the mucous membranes of the mouth with subsequent measurements of pain thresholds induced by argon-laser stimulation. Two different dosages (30 mg and 60 mg) of lidocaine spray were administered to the oral mucosa of the lower lip in healthy volunteers. Repeated measurements were performed until normal sensitivity returned after 15 min. Pain thresholds increased 62% after 30 mg lidocaine and 50% after 60 mg lidocaine (a non-significant difference). Thus repeated applications were found to be without any additional hypoalgesic effect. Maximal hypoalgesia was reached after 4 to 5 min. Complete analgesia was not obtained. The hypoalgesic effect lasted until 14 min, but painful procedures should be performed in the time interval 3-8 min after application. PMID- 1441879 TI - Increased volume of gastric contents in diabetic patients undergoing renal transplantation: lack of effect with cisapride. AB - Gastroparesis is a frequently unrecognized complication of insulin-dependent diabetes mellitus, which subjects these patients to the risk of aspiration at induction of anaesthesia. The effect of oral cisapride on volume and pH of gastric contents was studied in 24 diabetic and 24 non-diabetic uraemic patients undergoing renal transplantation. All patients were allocated randomly in a double-blind fashion to receive either 10 mg of cisapride or placebo orally approximately 100 min before anaesthesia and three times daily for the first 2 postoperative days. After the induction of anaesthesia, gastric contents were aspirated through a nasogastric tube, and the pH and volume were measured. The emptiness of the stomach was verified by gastroscopy. Gastric volumes exceeding 0.4 ml.kg-1 were observed in 12/24 of the diabetic and 4/24 of the non-diabetic uraemic patients (P < 0.01). The pH of the gastric contents did not differ between the groups, ranging from 1-8 in diabetics and 1-7 in non-diabetics. Cisapride lacked effect on gastric contents and postoperative gastrointestinal motility. Diabetic uraemic patients had larger gastric volumes than their non diabetic controls at induction of anaesthesia. Cisapride had no effect on gastric emptying preoperatively nor on postoperative bowel function. PMID- 1441881 TI - Ultrastructure of the parathyroid gland of fetal and pregnant golden hamsters subjected to hypergravity environment. AB - The ultrastructure of the parathyroid glands of fetal and pregnant golden hamsters exposed to 5-gravity environment was studied. In the centrifuged fetal animals the Golgi complexes associated with some prosecretory granules were significantly increased compared with those of the control fetal animals, and several secretory granules were located in a peripheral position just beneath the plasma membrane. In the centrifuged pregnant animals the Golgi complexes associated with numerous prosecretory granules were significantly increased, cisternae of the granular endoplasmic reticulum appeared to be increased compared with those of the control pregnant animals, many secretory granules were located in the peripheral cytoplasm and several granules were situated close to the plasma membrane. These findings suggest that in the parathyroid glands of the fetal golden hamsters as well as the pregnant animals the synthesis and release of parathyroid hormone may be stimulated in response to a hypergravity environment. PMID- 1441880 TI - Individual variability of pathological parameters in chemically induced rat colon tumors. AB - The development of tumorigenic conditions in the carcinogen-exposed rat colon was studied using selected morphological, histochemical, immunohistochemical and biochemical methods of analysis. Rats were treated with two carcinogens: 1,2 dimethylhydrazine and N-methyl-N'-nitro-N-nitrosoguanidine alone or with deoxycholic acid as a tumor promoter. It was found that 3 months after treatment of animals with the carcinogens the following changes were developed in colonic tissue: infiltration of lymphocytes in the mucous membrane, high increase in mitotic index among epithelial cells, negative reactions of colonic cells for neutral mucopolysaccharides and sulfomucins and positive reactions to carboxyl groups, nonsulfated acid mucosubstances and tissue polypeptide antigens. An increase in the activity of ornithine decarboxylase in colonic tissue was developed within the same time period and has been seen only in those tissues which were characterized by the development of precancerous conditions. Individual variations were observed in the manifestation of the studied parameters in rat neoplastic colonic tissues. It is suggested that these differences reflect an individual sensitivity of animals to carcinogens and the magnitude of the dysplastic processes induced in the colon. PMID- 1441882 TI - Degranulation of rough endoplasmic reticulum in M phase and adenosine triphosphate-treated interphase cells is reversible. AB - In the preferential harvesting of rounded mitotic (M phase) cells of human Chang liver monolayer cultures by mechanical agitation in Ca(2+)-free phosphate buffered saline, degranulation of endoplasmic reticulum (ER) was observed. Mitotic cells are known to have a series of Ca2+ transients and, without being subjected to Ca(2+)-free washings, did not have degranulated ER. Quiescent cells incubated with 0.7 mM adenosine 5'-triphosphate (ATP) in Ca(2+)-free HEPES buffered saline produced very similar ER degranulations. Confocal argon laser imaging of fluo-3-loaded cells showed a Ca2+ transient peaking at 2 min after ATP treatment. In the absence of extracellular Ca2+, transients of Ca2+ elevation in the cytosol would exit the cell in a down-gradient, draining the ER Ca2+ stores. Substituting ATP with 1 microM brominated A23187 calcium ionophore in the incubation that contained 1-100 mM CaCl2, respectively, did not produce ER degranulation, thereby excluding raised cytosolic Ca2+ per se as the cause of ER degranulation. In fact, incubation with 0.7 mM ATP in the presence of 1-5 mM CaCl2 failed to produce ER degranulation. ER degranulated cells, from treatment with ATP without extracellular Ca2+ as well as from Ca(2+)-free washings at M phase, could be rescued by subsequent incubation in growth medium that contains Ca2+ whereupon the rounded cells re-flatten (a round-to-flat change) and have well-defined rough ER. It therefore seems possible for Ca2+ depletion, or at least a reduction, to be causally related to ER degranulation. If that were the case, ER granularity would appear to be a facultative rather than a constitutive state. PMID- 1441883 TI - Gamma-aminobutyric acid immunoreactivity in the enterochromaffin cells of the rat stomach. AB - The present immunocytochemical study revealed gamma-aminobutyric acid (GABA) immunoreactivity in the oxyntic and pyloric mucosa of the rat stomach at light- and electron-microscopic levels. GABA-immunoreactive endocrine cells were numerously seen in the lower half portion of the pyloric mucosa but rarely in the oxyntic mucosa. These cells were round or oval in shape and sometimes had a short cytoplasmic process. Serotonin-immunoreactive enterochromaffin (EC) cells were also observed in the oxyntic and pyloric mucosa of the stomach. The distribution and shapes of the immunoreactive cells were similar to those of the GABA immunoreactive cells. With a double immunolabeling technique using anti-GABA and antiserotonin serum, GABA-immunoreactive endocrine cells showed serotonin immunoreactivity and were identified as EC cells. At the electron-microscopic level the GABA-immunoreactive cells contained round or oval, spindle-like, pear shaped granules in EC cells. The immunoreaction product in the EC cells was generally confined to the granular cores. These findings suggest that GABA may be synthesized in the EC cells and be released from the granules of the cells after adequate stimuli. PMID- 1441884 TI - The mandible--an analysis. AB - In this study, an attempt has been made to examine and analyse the ancient mandibles of people who have died several hundreds of years ago during the second and first millenium B.C. These mandibles have been recovered from the burial mounds in Bahrain (Arabian Gulf) and preserved in the National Museum and the Department of Antiquities in Bahrain. The dental conditions recorded are e.g. attrition, caries, fluorosis, periodontitis or antemortem tooth loss. The results indicate the age, sex, diet, occupation and environmental conditions that existed and even the culture of the people. A comparative study of the ancient mandibles and those of the present generation has been carried out. PMID- 1441885 TI - Distributions of antibovine-pepsinogen-positive cells in glandular regions of forestomach in the bactrian camel, Camelus bactrianus. AB - The present paper describes mucous cells in the forestomach glandular region which immunoreacted to antibovine pepsinogen serum in adult and young bactrian camels, Camelus bactrianus (female, 25 years old; female, 6 months old; from Hilar Inner Mongolia, People's Republic of China, in August 1988). These immunoreactive cells in forestomach glandular regions also reacted to Alcian blue (pH 1.0) and/or periodic acid-Schiff. Cross-reactivity of antibovine pepsinogen serum against extracts from the forestomach glandular region was analyzed by Western blotting, supporting that this serum could detect pepsin and/or pepsinogen in the bactrian camel. It was suggested that mucous cells in forestomach glandular regions produce pepsinogen molecules. PMID- 1441886 TI - Cartilage canal growth: experimental approach in the rat tibia. AB - This paper studies the influence of an antimitotic factor (puromycin) and a hormonal factor (thyroid hormone, TH) on canal growth. The tibiae of 15 six-day old rats were cultured in a serum-free chemically defined medium. The cultures were carried out for as long as 6 days. Our results show: (1) canal growth is not dependent on perichondrium or chondro-epiphysis growth; (2) the canal is greater and has a complex pattern in a triiodothyronine (T3)-treated assay group; (3) round and multinucleated cells are more numerous in the T3-treated assay group than in the other groups. We hypothesize that the canal grows by a physiological phenomenon of programmed cell death and that it is stimulated by TH. PMID- 1441887 TI - Distribution of glycoconjugates localized by peanut and Maclura pomifera agglutinins during mouse molar root development. AB - Glycolipids, glycoproteins, glycosaminoglycans and sialoglycoproteins have all been implicated in a number of developmentally significant processes related to complex interactions between cell surfaces and the extracellular matrix. The present study was designed to localize glycoconjugates recognized by peanut agglutinin (PNA) and Maclura pomifera (MPA) lectins during mouse molar root development. Postnatal ICR mice at 10, 15, 21, 28 and 42 days were used. Lower jaws were dissected, fixed in 4% paraformaldehyde, decalcified in 5% EDTA and embedded in paraffin. Serial sections were made and stained with FITC-conjugated PNA or MPA. beta-Lactose was used as an inhibitory sugar for PNA, and alpha-D melibiose for MPA. PNA specifically stained Hertwig's epithelial root sheath (HERS), whereas MPA stained a number of tissues. The outermost layer of root dentin, forming cellular cementum, alveolar bone and HERS showed positive reactions with MPA. Glycoconjugates localized by the lectins may be functionally related to molecules which contribute to root formation and cemento-genesis. PMID- 1441888 TI - Modulation of phenotype and cytoskeleton architecture by interleukin-1 alpha in human osteoblast-like cells in vitro. AB - Interleukin-1 alpha, a growth factor produced by macrophages as well as many other types of cells, is able to modulate biosynthetic activities in bone cells. In this work, the authors show that the administration of interleukin-1 alpha to osteoblast-like cells in vitro induces a marked change in cell morphology, which becomes dendritic, with a smaller cellular body and numerous prolongations. The morphological changes are also accompanied by an altered expression in the pattern of cytoskeleton proteins. PMID- 1441889 TI - Increase of DNA synthesis in uterine adenomyosis in mice with ectopic pituitary isograft. AB - Ectopic pituitary isografts (EPI) have been found to induce a high incidence of uterine adenomyosis in SHN mice. All the SHN mice given EPI in the right uterus at 40 days of age developed uterine adenomyosis, and more than 80% of mice showed the genesis of subserosal nodules, an advanced state of adenomyosis, 65 days after EPI. Activities of both thymidylate synthetase and thymidine kinase, i.e. DNA-synthesizing enzymes in de novo and salvage pathways of pyrimidine metabolism, respectively, were significantly increased in EPI-induced uterine adenomyosis to approximately 2-fold those in normal control uteri. Bromodeoxyuridine-immunoreactive cells were regarded as the cells in S phase, and the number in the endometrial epithelium and stroma in EPI-induced uterine adenomyosis was more than 1.5-fold that in normal control uteri. EPI may affect the genesis of uterine adenomyosis generally, but not locally, because there were no differences between the right uterus with EPI and the left without EPI in the incidence of adenomyosis, histology or DNA-synthesizing enzyme activities. PMID- 1441890 TI - Identification of sugar residues in human fetal olfactory epithelium using lectin histochemistry. AB - Lectin-binding histochemistry was used to investigate the distribution and the changes of the glycoconjugate saccharidic moieties in the olfactory epithelium of human fetuses ranging from 8 to 12 weeks of gestation. It was found that the basal cells, the sustentacular cells and the olfactory neurons exhibit differences in oligosaccharide cellular content and distribution. Differences in lectin binding was also demonstrated at the dendrite, cell body and axon of the receptor cells. From the 11th week onwards, Ulex europaeus agglutinin I was found to be a marker of the olfactory neurons. PMID- 1441891 TI - Clomiphene citrate alters surface ultrastructure of uterine luminal epithelial cells. AB - Scanning electron microscopy was used to evaluate the uterine luminal epithelium from ovariectomized rats treated with a single minimal physiological dose of clomiphene citrate, oestradiol-17 beta or progesterone. It was found that clomiphene treatment produced some ultrastructural surface features which were similar to those seen with both oestrogen and progesterone treatment, but in addition it produced features unique to clomiphene treatment. PMID- 1441892 TI - Are Ranvier's nodes of the central nervous system also artifacts by preparation? AB - Recent research on peripheral nerves of six species of vertebrates concluded that Ranvier's nodes may be artifacts by preparation. As a consequence, the question as to whether or not Ranvier's nodes of the central nervous system may also be artifacts was logically raised. The ultrastructural data concerning our field of research (the cerebellar cortex) support the notion that Ranvier's nodes are real features in the central nervous system; otherwise, the occurrence of vesicular outpockets establishing, along myelinated axons, well conspicuous en passant nodal synapses cannot be explained. PMID- 1441893 TI - Isolated pancreatic islets of the rat: an ultrastructural study. AB - Pancreatic islets from adult Wistar rats were isolated by an improved collagenase digestion technique. Examination of the preparations showed that they contained B cells possessing secretory granules, each having an eccentric electron-dense core surrounded by an electron-lucent halo; the Golgi bodies with their characteristic features were located in a juxtanuclear position. Roughly surfaced endoplasmic reticulum and mitochondria were present and were mostly normal in appearance. The cell possessed all the ultrastructural attributes indicating that they were fully functional and structurally intact. PMID- 1441894 TI - [Quantitative analysis of the isthmo-optic nucleus and projection neurons to the retina in adult fowl (Gallus gallus domesticus)]. AB - Quantitative analysis of the isthmo-optic nucleus (IO) and centrifugal projection to the retina in the fowl was made using Nissl preparation and retrograde horseradish peroxidase (HRP) methods. Seven adult fowls (Gallus gallus domesticus) were used for Nissl stain. Serial sections were cut on a freezing microtome at 60 microns and stained with cresyl violet. IO was situated just medial to the caudal part of the tectum and laterodorsal surface of the brain stem. Rostrocaudal extension of IO was about 800-1,000 microns. The average total volume and neuronal population of the IO was 280 x 10(-3) mm3 and 5,600 neurons, respectively. Eight animals were used for HRP study. One hundred microliters of 30% HRP solution in physiological saline was injected into the vitreous body of one eye of each hen. Serial transverse sections of 60 microns were treated with tetramethyl benzidine (TMB). Many labeled neurons were found in contralateral brain stem. Average total number of contralateral HRP-labeled cells in IO and peri-IO were 5,268 and 1,492, respectively. Labeled neurons peri-IO were mainly distributed ventrally and rostrally to IO. No labeled neurons in IO, and only a few labeled neurons peri-IO were found ipsilaterally. The number of HRP-labeled neurons in IO corresponded to the neuronal population of IO in Nissl preparation, which suggested that most of isthmo-optic neurons might be projecting to the contralateral retina. In contrast to the round and small IO neurons (long axis 15 20 microns, short axis 10-20 microns), peri-IO neurons were multipolar and longer (long axis 15-30 microns, short axis 10-25 microns). PMID- 1441895 TI - [Cellular architecture of the sheep myocardium and heart conduction system as revealed with silver-impregnation method]. AB - Morphological studies were carried out to delineate the cellular architecture of the myocardium and heart conduction system in adult sheep using the silver impregnation method. Reticular fibers were heavily stained in a deep black color, while collagen fibers were less intensely silver-stained in a brownish color. Individual working myocardial cells were ensheathed by thin reticular fibers and showed a polygonal form, and were connected with adjacent cells mainly end-to-end and sometimes side-to-side. Thick collagen septa were distributed between masses of myocardial cells. The nodal cells in both the sinoatrial (SA) node and atrioventricular (AV) node were spindle shaped, smaller in size than myocardial cells, and surrounded by thin reticular fibers. The bundles of SA node cells were linearly oriented, while those of AV node cells formed a reticular pattern. The cells in the His bundle and Purkinje system were oval in shape, larger in size than myocardial cells and formed the strands composed of 4-8 cells. Each stand was surrounded by thick reticular fibers. These cells had both end-to-end and side-to-side contacts. Purkinje cells were followed by transitional cells which were in contact with myocardial cells. On the other hand, the reticular fibers and collagen fibers showed characteristic structures at the different portion of heart. The present study discusses the topographical relationship between cardiac muscle cells containing the conduction system and the connective tissue sheaths surrounding muscle cells. PMID- 1441898 TI - [A research and simulation study on the cadaver supply for education and research]. PMID- 1441897 TI - [The selachian terminal nerve]. AB - In order to clarify morphology and function(s) of the terminal nerve, gross examinations of the nerve were carried out in 9 species of selachians. The terminal ganglion was observed light- and electron-microscopically. FMRF-amide immunoreactivity of the terminal nerve was also examined in some species. The results were as follows: 1) The terminal nerve was divided into peripheral and central branches by interposed ganglion(s). Macroscopically, the peripheral branch appeared from an area between the nasal sac and the olfactory bulb. The central branch entered the telencephalon from either the rostral, dorsal, or ventral surface. The position seemed to differ from species to species. 2) The terminal nerve showed great species differences and individual variations in the macroscopic morphology, such as number and course of the peripheral branch, position, size and number of ganglia, and telencephalic areas where the central branch entered. Even in the same individual, there was a difference in left and right sides. 3) According to general histology, the ganglion was encapsulated and had no direct connection with the telencephalon through the capsule, even when the ganglion was situated on the telencephalon. The Bodian preparations showed that most ganglion cells were unipolar, and a few were bipolar or pseudounipolar. 4) All ganglion cells and the processes were FMRF-amide immunoreactive. Immunoreactive fibers of the central branch terminated in the septal and preoptic areas. FMRF-amide immunoreactive cells were also found in the olfactory nerves or the septal area of the telencephalon in some species. These neurons were thought to be ectopic ganglion cells. 5) Neuronal somata and the axons in the ganglion contained large dense cored vesicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441896 TI - [On the fenestration of the vertebral and basilar arteries]. AB - The fenestration of the vertebral and basilar arteries was investigated macroscopically in 370 human cases. Altogether 43 fenestrations were found in 32 (8.6%) out of 370 cases. The fenestrations could be divided in three groups according to the position where the fenestration appeared. Group I was the fenestration observed along the vertebral artery (Fig. 1), and 7 such fenestrations were found in 6 (1.6%) out of 370 cases; 3 fenestrations among them were located on the right side, 2 were located on the left side and 1 was found on the bilateral vertebral arteries. In 4 out of 7 fenestrations in this group, the hypoglossal nerve was found passing through the fenestration. Group II was the fenestration observed along the basilar artery (Fig. 2), and 26 fenestrations of this type were found in 20 (5.4%) out of 370 cases: 23 fenestrations (88.5%) were located at the caudal half, 3 (11.5%) were located on the rostral half of the basilar artery (Fig. 5). A close relation was indicated between the side on which the fenestration appeared in the basilar artery and the largeness in caliber of the vertebral artery of either side. Group III was the fenestration observed at the lateral area of the vertebral and basilar arteries (Fig. 3), and 10 fenestrations of this type were found in 9 (2.4%) out of 370 cases; all the fenestrations were located on the right side. In this group, the hypoglossal nerve was observed passing through the fenestratin in 4 out of the 10 fenestrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441899 TI - Magnetic resonance studies on brain dysfunction induced by organic solvents. AB - A 38-year-old layer of parquet flooring was referred because of memory impairment, tiredness and diffuse headaches. His work involved using several neurotoxic organic solvents. Extensive laboratory, neuropsychological, clinical neurophysiological, neuroadiological, magnetic resonance (MR) imaging and spectroscopy studies were performed. The neuropsychological and behavioural assessments showed an organic brain syndrome. MR imaging and CT scanning of the brain revealed enlarged ventricles and generalized atrophy. 31P and 1H MR spectroscopic measurements did not show any abnormalities. Owing to recent improvements regarding sensitivity and facilitated assignment, MR spectroscopy may provide in the near future significant additional information on brain metabolism in patients with brain dysfunction presumably induced by organic solvents. PMID- 1441901 TI - Apraxia of eyelid opening secondary to right frontal infarction. AB - Apraxia of eyelid opening is the incapacity of voluntarily eyelid opening in the absence of motor dysfunction or blepharospasm. It has mostly been described in extrapyramidal diseases and only very rarely in cortical lesions. We report a right-handed patient with a right frontal infarction exhibiting eyelid opening apraxia. PMID- 1441900 TI - Treatment of idiopathic inflammatory myopathies with cyclophosphamide pulses: clinical experience and a review of the literature. AB - Short-term cyclophosphamide pulse therapy was administered to five patients with idiopathic inflammatory myopathies (IIM) which were refractory to corticosteroids and, in two cases, to other aggressive therapies. Both disease remission and a reduction in corticosteroid dosage were obtained in four patients. Three of them have been in remission over since, taking only minimal doses of steroids during the subsequent two years. In the fourth patient a less intensive, maintenance pulse therapy could not be continued due to unacceptable side effects. On the basis of these results and of data from the literature, herein reviewed, cyclophosphamide pulse therapy may be recommended for adult patients with IIM who do not respond to or who do not tolerate conventional corticosteroid treatment, as well as when a steroid-sparing effect is desired. PMID- 1441903 TI - Epilepsy care in The Netherlands. AB - In this article models of epilepsy care in the Netherlands are outlined. Mostly this care is aimed at people with uncontrolled epilepsy who may have suffered from the adverse effects of ignorance, prejudice and even discrimination. Many of these adverse factors should be avoidable in future as the educational programmes for people with epilepsy, professionals and the general public take full effect. Meanwhile there is a great deal that can be done to rehabilitate people whose seizures are a problem and whose social abilities fall short of the standards that are required for independent and self-fulfilling living in any society. The models of care described are very sophisticated and they have been developed over many years. They require well-trained and motivated staff and sometimes elaborate and expensive medical diagnostic equipment. But this should not put anybody off as the principles behind any model of care should be the same: Accurate diagnosis. Optimal drug and other treatment (this should be optimal treatment available in that country). Education of the patient and family about all aspects of epilepsy. Opportunity to share experiences. A multidisciplinary approach to identified problems (a multidisciplinary approach can be taken by one person, although a team of people from different disciplines is ideal.) Objectives agreed by all participants. PMID- 1441902 TI - Sneddon's syndrome associated with anticardiolipin antibody: a case report. AB - We report the case of a young man suffering from the rare combination of livedo reticularis and recurrent ischemic cerebrovascular disease (Sneddon's syndrome). He also had a circulating anticardiolipin antibody. in the absence of systemic lupus erythematosus, we suggest the likelihood of a primary antiphospholipid syndrome. PMID- 1441904 TI - The relationship of neuropsychological abilities to seizure factors and to surgery for epilepsy. PMID- 1441905 TI - The effect of seizure activity and paroxysmal electroencephalographic discharges on cognition. PMID- 1441906 TI - Epileptic equivalents in psychiatry: some 19th century views. PMID- 1441907 TI - Affect and mood in epilepsy: an overview with a focus on depression. PMID- 1441908 TI - Childhood epilepsy: pharmacological considerations. PMID- 1441909 TI - The Heemstede tradition of clinical neurophysiology. PMID- 1441910 TI - Genetic research in epilepsy: the Italian League against Epilepsy contribution. PMID- 1441912 TI - Recent advances in surgical treatment of temporal lobe epilepsy. PMID- 1441911 TI - Current medical therapy of epilepsy. AB - The treatment of epilepsy firstly depends upon the correct diagnosis, with emphasis on considerations of etiology, seizure type, and epilepsy syndrome. Following an appropriate diagnostic conclusion, the patient may be started on the medication matched to the seizure type. A full understanding of the pharmacology of antiepileptic drugs will enable the physician to obtain maximum benefit from the available pharmaceutical armamentarium. PMID- 1441913 TI - Classification of epileptic seizures and the epilepsies. PMID- 1441914 TI - Extratemporal epilepsy: clinical presentation, pre-operative EEG localization and surgical outcome. AB - To summarize, the most commonly encountered problems in the pre-operative EEG localization of the epileptogenic zone in patients with extra-temporal epilepsy are dependent upon: 1) Poor EEG localization of the interictal epileptic abnormality and poor localization of seizure onset. 2) Presence of a widespread epileptogenic area during interictal and ictal tracings, often involving two or more lobes synchronously or independently, thus suggesting a multilobar or a multifocal epileptic disorder. 3) Absence or paucity of interictal epileptiform discharges is not an uncommon finding and clinical seizures without accompanying ictal EEG manifestations are also not uncommon. 4) Different paths of seizure propagation might occur even in individual patients. This may reflect clinically as different seizure patterns resembling a multifocal seizure problem. From this review, one could envisage that the future research challenge in extra-temporal epilepsy resides in the development of a technology or system which will provide a better localization of the seizure generator, as well as a better identification of the mechanisms of seizure spread, ideally indicating anatomical pathways involved. PMID- 1441915 TI - Epilepsy services. What people need, what they want, what they get. PMID- 1441917 TI - Morphometric study of the sensory neuron and peripheral nerve changes induced by chronic cisplatin (DDP) administration in rats. AB - We performed a morphological, morphometric and toxicological study on the spinal ganglia and peripheral nerves of the rat after chronic administration of cisplatin (cis-dichlorodiammineplatinum II; DDP) with two different schedules. Severe damage of the spinal ganglia neurons was demonstrated with predominant involvement of the nucleus and nucleolus associated with a decrease in the cell size. Morphological and morphometric changes also occurred in the sciatic and peroneal nerves with the features of axonopathy. All these changes were more marked in the group of rats which underwent the most intense DDP treatment and the tissue platinum concentrations were also higher in this group. This experimental model is the first available for chronic DDP administration in which concomitant spinal ganglia and peripheral nerve damage has been confirmed pathologically. Our study supports the hypothesis that DDP-induced peripheral nerve fiber degeneration may result from nuclear and nucleolar changes in the sensory ganglion cell perikaryon. PMID- 1441916 TI - Neuron-associated class III beta-tubulin isotype, retinal S-antigen, synaptophysin, and glial fibrillary acidic protein in human medulloblastomas: a clinicopathological analysis of 36 cases. AB - Surgical specimens from 36 medulloblastomas (25 classic and 11 desmoplastic) were studied by peroxidase-antiperoxidase (PAP) immunohistochemistry with antibodies against the class III beta-tubulin isotype (beta-tubulin), synaptophysin, retinal S-antigen (S-Ag), and glial fibrillary acidic protein (GFAP). We found that neoplastic cells expressed beta-tubulin in 91% of the tumors (23 classic and 10 desmoplastic), synaptophysin in 75% (19 classic and 8 desmoplastic), S-Ag in 44% (11 classic and 5 desmoplastic), and GFAP in 11% of medulloblastomas (2 classic and 2 desmoplastic). Synaptophysin and beta-tubulin positivities were observed in undifferentiated neoplastic cells, in cells forming neuroblastic rosettes, and in pale islands, while S-Ag immunopositivity was noted in undifferentiated cells, occasionally in beta-tubulin-negative neuroblastic rosettes, and exceptionally in pale islands. Large pale islands, in two desmoplastic medulloblastomas, exhibited distinct patterns of immunoreactivity to the above markers, suggesting neuronal and glial differentiation in the central area, and intense neuritic development in the peripheral zone. Our findings confirm the predominant capacity of medulloblastoma cells to differentiate along neuronal cell lines and indicate that large pale islands, in desmoplastic medulloblastomas, represent well organized areas for neuronal and, to a lesser degree, astroglial differentiation. Furthermore, it appears, in our cases, that immunohistochemical features do not represent clear-cut prognostic indicators in patients with medulloblastomas. PMID- 1441918 TI - Amyotrophic lateral sclerosis with ophthalmoplegia and multisystem degeneration in patients on long-term use of respirators. AB - We describe two patients with sporadic amyotrophic lateral sclerosis (ALS), who had developed progressive external ophthalmoplegia of a predominantly supranuclear type while they survived on respirators, and displayed histopathological abnormalities both typical and atypical of ALS. Patient 1 was a 43-year-old man with ALS of 5-year duration, who had initially exhibited fulminant ALS, and remained on a respirator for 4 years. Patient 2 was a 51-year old man with ALS of 13-year duration, who remained on a respirator for 8 years. Both patients died in a "totally locked-in state". Autopsy of both patients revealed not only histopathological abnormalities consistent with ALS, but also multisystem degeneration which involved the pontine tegmentum, substantia nigra, Clarke's dorsal nuclei and spinocerebellar tracts. In addition, Patient 2 displayed intracytoplasmic neuronal basophilic inclusion bodies which exhibited marked immunoreactivity to anti-ubiquitin antibodies. Our case reports indicate that the longer survival which is possible through the use of respirators may make one subgroup of ALS patients prone to develop atypical clinical and neuropathological features which are not observed during the natural course of ALS. PMID- 1441919 TI - The characteristics of blood-brain barrier in three different conditions- infarction, selective neuronal death and selective loss of presynaptic terminals- following cerebral ischemia. AB - We investigated the extravasation of serum albumin using immunohistochemistry in three different conditions, i.e., infarction, selective neuronal death and selective loss of presynaptic terminals following cerebral ischemia in gerbils. In selective neuronal death, which is typically found in the CA1 neurons of the hippocampus after 5-min bilateral cerebral ischemia, selective damage of postsynaptic components with intact presynaptic sites was demonstrated by immunohistochemical examination for microtubule-associated protein 2 and synapsin I, and albumin extravasation did not become apparent before postsynaptic structures were destroyed. In cerebral infarction, which was consistently observed in the thalamus after 15-min forebrain ischemia, massive albumin extravasation was visible early after ischemia due probably to the ischemic endothelial necrosis. In selective loss of presynaptic terminals, which was detected at the molecular layer of the dentate gyrus in the contralateral, nonischemic hippocampus after unilateral cerebral ischemia, immunoreaction for albumin was not visualized. Since endothelium and glial cells were intact in morphological aspects in selective damage of both pre- and postsynaptic sites, it was thought that extravasation was facilitated by the stimulation of endothelial cells and glial cells with unknown factors that were induced by the destruction of post- but not presynaptic elements. PMID- 1441920 TI - Immunohistochemical observations on rat radial glia: relationship with the origin of ethylnitrosourea-induced tumors. AB - Gliomas induced in the rat by transplacental administration of ethylnitrosourea (ENU) are intensely immunoreactive for vimentin and scarcely for glial fibrillary acidic protein (GFAP). Since tumoral transformation takes place during the late fetal and early postnatal period, the sequential expression of the two glial antigens has been investigated in this age period in ENU-treated and control rats. Immunohistochemical and immunoelectron microscopical methods have been employed. Vimentin was widely expressed starting from embryonal day 14 (E 14) in the processes of radial glia; as long as radial glia was present, vimentin decorated it. GFAP was, at earliest, observed at E 20 and expressed by glial cells with a stellate, i.e., mature shape. No GFAP-positive radial process was observed. No difference was found between ENU-treated and control rats. Since ENU is most effective in producing tumors when administered at the 16-17th day of fetal life, vimentin-positive radial glia is a candidate target of ENU. The similarity of intermediate filament pattern between radial glia in the late fetal life and tumors induced by transplacental ENU suggests that radial glia might be the cell of origin. PMID- 1441921 TI - Immunoelectron microscopic study of tubulin and microtubule-associated proteins after transient cerebral ischemia in gerbils. AB - Differential vulnerability of microtubule components to cerebral ischemia has been reported previously. We investigated the disintegration of microtubules using immunoelectron microscopy for alpha-tubulin and microtubule-associated protein 1A and 2 (MAP1A and 2). Mongolian gerbils were subjected to bilateral carotid occlusion for 10 to 30 min and reperfusion for up to 72 h following ischemia for 10 min. After ischemia for 10 min, some dendrites in the stratum moleculare of the subiculum-CA1 region lost immunoreaction products for alpha tubulin and MAPs. Loss of the reaction products spread to the medial CA1 region during progressive ischemia for 30 min. In some dendrites, electron-dense precipitates for MAPs were dispersed in the dendritic cytoplasm with little reaction product on microtubules and without alteration of the reaction for alpha tubulin. After recirculation, loss of electron-dense precipitates for alpha tubulin and MAPs, as well as disintegration of microtubules, propagated further to the medial CA1 region and to the proximal dendrites. The present study demonstrated prompt disintegration of microtubules with rapid disappearance of the reaction for MAPs which seemed to be caused by detachment of MAPs from the microtubule cores. PMID- 1441922 TI - Spasmodic torticollis: severe compression neuropathy in rami dorsales of cervical nerves C1-6. AB - In 28 patients with spasmodic torticollis dorsal branches of the cervical nerves C1-6, and in 25 of these patients fascicles of the contralateral accessory nerve were investigated by light and electron microscopy. Significant changes were noted in 15 patients. The alterations were not seen or were less prominent in the 5 control cases studied for comparison. Semiquantitative evaluation of light microscopic findings revealed in 12 cases prominent and numerous Renaut bodies; in 9 cases evidence of regeneration (in 3 of these postoperatively); and in 11 cases disproportionately thin myelin sheaths in relation to axon calibers. In conjunction with endoneurial edema and thickening of the perineurium, these changes were suggestive of compression neuropathy. Whether these changes were the cause, or a side effect of the abnormal muscle contractions in spasmodic torticollis could not be elucidated. Peripheral nerve compression, however, may trigger abnormal activity in the peripheral part of the involved interneuronal circuits and may, thus, be considered as one of the many possible causes of spasmodic torticollis. PMID- 1441924 TI - Occurrence of active demyelinating lesions in children with hereditary motor and sensory neuropathy (HMSN) type I. AB - In three children with dominant hereditary motor and sensory neuropathy type I, peripheral nerve biopsy showed the classical lesions of segmental demyelination with remyelination and onion bulb formations. In two cases, ultrastructural examination also demonstrated numerous characteristic features of active demyelination. The presence of active demyelinating lesions suggests an autoimmune attack superimposed on the course of a chronic genetic disease. PMID- 1441923 TI - Occurrence of acetylcholinesterase activity closely associated with amyloid beta/A4 protein is not correlated with acetylcholinesterase-positive fiber density in amygdala of Alzheimer's disease. AB - To investigate the possible relationship between acetylcholinesterase (AChE) containing fiber density and senile plaque density and between AChE-positive plaques and beta/A4 protein deposition, AChE histochemistry, the modified Bielschowsky's method and beta/A4 protein immunohistochemistry were performed on the amygdala of Alzheimer's disease (AD) and aged control cases. Abundant AChE positive senile plaques were found in the amygdala and related structures in AD. These AChE-positive plaques were mainly of the primitive or diffuse type. In addition to senile plaques of typical morphologies a variety of AChE-positive structures were observed in the amygdala and related regions in AD. A comparison of serial sections stained alternatively with AChE histochemistry and beta/A4 protein immunohistochemistry has revealed that these AChE-positive structures with variable morphological appearances displayed beta/A4 protein immunoreactivity, indicating that AChE is localized in a variety of beta/A4 protein deposition including the diffuse plaque. Thus, it is suggested that AChE is present in some senile plaques at the earliest stage. However, there was no apparent correlation between the numerical density of AChE-positive fibers and senile plaque density. These findings suggest that the degeneration of cholinergic neurons is not attributed to the occurrence of AChE activity in beta/A4 protein. PMID- 1441926 TI - Ciliary claws: their existence in various epithelial cysts of the central nervous system. AB - We describe claw-like projections and their associated structures as encountered at the tips of cilia in a cerebellar epithelial cyst, an intraspinal bronchogenic cyst and two colloid cysts of the third ventricle. Ciliary claws appear either as a single structure or as a cluster of two to five projections measuring 22-28 nm in length and 8-10 nm in diameter, extending from the plasma membrane of the ciliary tip. The transmembranous fibrils of the ciliary claws are bound to a multilayered electron-dense disc which is attached by the distal ends of axonemal microtubules. These observations suggest that ciliary claws are common in several types of epithelial cysts of the central nervous system; the presence of these structures supports the premise that the corresponding epithelium is of endodermal origin. PMID- 1441925 TI - Cumulative white matter changes in the gerbil brain under chronic cerebral hypoperfusion. AB - An animal model of chronic brain hypoperfusion has been developed by applying coiled clips to the bilateral carotid artery of Mongolian gerbils. The brain tissue damage was neuropathologically studied after 1, 4, 8, and 12 weeks of hypoperfusion. The hippocampus, basal ganglia, and cerebral cortex of the chronically hypoperfused gerbil showed lesions with various severity which are probably due to ischemic episodes. In the cerebral white matter, however, two types of lesions were observed; one similar to those in the gray matter, and the other observed only in the white matter after more than an 8-week duration of brain hypoperfusion. The lesion specific to the white matter showed rarefaction and gliosis without locally associated ischemic changes. This type of the white matter lesion was never found in the gerbil brain before 8 weeks and, significantly, increased in number and size by 12 weeks post operation. The accumulation of the white matter lesions is characteristic in the gerbil with chronic hypoperfusion. The observed white matter-specific lesion resembles the histological changes in aged brain with cerebrovascular diseases. PMID- 1441927 TI - Immunohistochemical evidence of endothelin-1 in human choroid plexus. AB - An immunohistochemical investigation was carried out on 17 specimens of human choroid plexus obtained post mortem, 1 biopsy of normal choroid plexus including part of the lateral ventricle and 1 papilloma of the choroid plexus removed surgically. The material was fixed in formalin. Paraffin and cryostat sections were used. A polyclonal antiserum to endothelin-1 served as a primary antibody. The avidin-biotin-peroxidase method was applied to demonstrate the immunoreaction. The epithelial cells of the choroid plexuses, the choroid papilloma and most ependymal cells of the lateral ventricle showed a distinct brown reaction product in their cytoplasm indicating antigenic sites to endothelin-1. The reaction was of lesser intensity in the ependymal cells. The connective tissue in choroid plexus was unstained. A positive immunoreaction was present in the walls of some vessels in the choroid plexus in cryostat sections. This is the first report on the presence of antigenic sites to endothelin-1 in the epithelial cells of the human choroid plexus. The role of endothelin in these cells should be investigated to ascertain if the cells synthesize this biologically active peptide or if it is merely bound to receptors in them. PMID- 1441928 TI - Neuropathology of biotinidase deficiency. AB - A patient with biotinidase deficiency and a progressive neurological disorder died just before the biochemical diagnosis was established. Post-mortem examination of the brain and spinal cord revealed necrotising lesions similar to those in Leigh's disease and Wernicke's encephalopathy. Unlike these two conditions, the regions affected included the hippocampus and parahippocampal cortex. In addition there was severe focal oedema in deep cerebral grey matter, the brain stem, and the spinal cord. These lesions appear to result from a number of severe metabolic disturbances, perhaps linked to an underlying disordered pyruvate metabolism. The nature of the pathology explains why a neurological deficit may persist despite treatment. PMID- 1441929 TI - Subtraction radiography of interradicular bone lesions. AB - Subtraction and conventional radiography were evaluated for their diagnostic potential to assess interradicular bone lesions in the mandibular premolar region. Both conventional radiographs and subtraction images were interpreted by 10 observers. The receiver-operating characteristic (ROC) technique was used to compare the two techniques. The diagnostic validity was higher for the subtraction technique, both for lesions confined to cancellous bone and for lesions including the cortical bone, than for the conventional technique. For bone defects confined to cancellous bone the diagnostic accuracy was lower than those reported from periapical bone lesions irrespective of whether subtraction or conventional radiography was used. We conclude that subtraction radiography improves the detectability of bone lesions, shallow ones in particular. Lesions in the interradicular bone are more difficult to detect than those in the periapical bone. PMID- 1441930 TI - Dental caries in primary school children in Nairobi, Kenya. AB - The purpose of this study was to record the caries status in children attending public primary schools in Nairobi. The sample comprised 513 children, 262 aged 6 8 years and 251 aged 13-15 years. The children were drawn from six randomly selected schools in the city. Clinical examination was carried out in a room with natural daylight, using the WHO (1977) criteria. Fifty-four per cent of the 6- to 8-year-olds and 50% of the 13- to 15-year-olds were caries-free. The mean dmft in the 6- to 8-year-olds was 1.7, and the mean dmfs was 3.5. The mean DMFT in the 13 to 15-year-olds was 1.8, and the mean DMFS was 2.9. The d- and D-components dominated and were mainly located in the occlusal surfaces. The f-component of the dmft and the F-component of the DMFT comprised 1% and 10%, respectively. There was no statistically significant difference (p > 0.05) in the prevalence of caries between males and females in the younger age group. In the older age group, however, females had a higher (p < 0.05) prevalence than males. In general, the study showed a low caries prevalence in Nairobi children. PMID- 1441931 TI - An experimental model of osteoarthrosis in the temporomandibular joint of the rabbit. AB - Degenerative changes in the temporomandibular joint were induced in 24 rabbits by surgical perforation of the disk. The incongruence obtained between the joint surfaces caused a gradual increase in macroscopic and microscopic changes, including gross remodeling, loss of tissue volume, and altered cell morphology within a 16-week observation period. These changes occurred concurrently with major alterations in the composition of the matrix, as demonstrated by increase in the glycosaminoglycan content of both condylar cartilage and disk and by loss of hydroxyproline in the disk. The lesions in the disk tissue were clearly discernible, whereas those in the condylar cartilage were less extensive. The described method is concluded to give alterations in the temporomandibular tissues, as seen in degenerative joint disease of an early stage. PMID- 1441932 TI - Craniomandibular disorders in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. A clinical study. AB - Sixty-one subjects with rheumatoid arthritis, 61 with psoriatic arthritis, 61 with ankylosing spondylitis, and 61 healthy controls were examined with regard to subjective symptoms and clinical signs of craniomandibular disorders (CMD). The frequencies of most subjective and clinical variables were higher in all three disease groups than in the control group. Subjects with rheumatoid arthritis and psoriatic arthritis showed more frequent and severe signs and symptoms than subjects with ankylosing spondylitis. It is concluded that subjective symptoms and clinical signs of CMD are common in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis and are mainly caused by the respective general joint disease. None of the signs and symptoms is pathognomonic for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. PMID- 1441933 TI - Use of professionally administered fluoride among Danish children. AB - The objective of this study was to determine the use of professionally administered fluoride in Denmark in 1991. Of the 275 addressed Danish municipalities 98% returned the questionnaire. Ten per cent of the municipalities with public clinics were using systematic mouthrinses with 0.2% fluoride, compared with 25% of the municipalities without public clinics (p < 0.01). In comparison, 93% of the municipalities reported having used mouthrinses in 1985. Fluoride swabbing was used by 69% of the municipalities not using mouthrinses and by 47% of the municipalities still using fluoride mouthrinses (p < 0.02). Duraphat lacquer was used in 92% of all municipalities, fluoride gel in 3% and fluoride tablets in 8% of the municipalities. It is concluded that during the past 6 years the use of professionally administered fluoride among Danish children has changed from mass-prophylactic mouthrinses to maneuvers aimed more at the specific needs of the individual. PMID- 1441934 TI - Microleakage of indirect composite inlays. An in vitro comparison with the direct technique. AB - Microleakage occurring around directly and indirectly made class-II composite restorations was evaluated on extracted human premolars. Before the evaluation was made, the teeth were thermocycled and stained with an organic dye. Direct class-II composite restorations demonstrated extensive microleakage at their dentin cavosurface margins. Indirect class-II composite inlays luted with a dual curing composite cement displayed much less microleakage than restorations made using the direct technique. The use of glass-ionomer cement rather than composite cement as the luting material resulted in more microleakage. Rather than being a true microleakage, the leakage of glass-ionomer cement might be the result of a diffusion of the water-soluble organic dye in the water-based cement. The results suggest that the indirect composite technique is superior to the direct technique when it comes to reducing microleakage. PMID- 1441935 TI - Skeletal maturity, dental maturity, and eruption in young patients with Turner syndrome. AB - A major problem for patients with Turner syndrome is their small body height. The rapid biotechnologic development has now made treatment with growth hormone possible at a larger scale. The aim of this investigation was to evaluate skeletal maturity, dental maturity, and eruption in a group of young patients before hormone therapy. The material comprised 33 patients aged 7-16.7 years. The skeletal maturity, as judged from hand radiographs, was on an average 2.3 years retarded (p < 0.001) and showed increasing retardation with increasing age. The dental maturity, assessed from the formation stages of the permanent teeth on panoramic radiographs, was accelerated, with a mean value of 1 year (p < 0.001). The timing of clinical eruption did not differ significantly from that of our reference material; the Turner girls were on an average 3.7 months ahead. Several patients had local eruption problems, especially in the maxillary lateral segments. It is suggested that disharmony between tooth size and arch size may contribute to this problem. PMID- 1441936 TI - Piezoelectricity in dental materials, a conceivable cause of postrestorative sensitivity. AB - With the increased use of tooth-colored posterior inlays reports of postrestorative sensitivity have also increased. One of the symptoms the patients complain of is a sharp pain when the inlays are loaded through chewing and biting. Many explanations for the causes of dissimilar types of postrestorative sensitivity have been offered, but one conceivable explanation that has not hitherto been studied is the direct piezoelectric effect in dental materials. Direct piezoelectric effect means that when certain anisotropic crystals are mechanically loaded, a charge is generated on the surface. The aim of the present study was to examine whether this physical phenomenon occurs in certain materials intended for dental use. Specimens of four different dental ceramics and one indirect composite resin for inlays were mechanically loaded with various forces, and the current was directly recorded. Currents of up to 0.9 microA with a pulse duraton of 0.4 msec were extracted, and it cannot be excluded that the piezoelectric phenomenon and related properties may cause postrestorative sensitivity. This has to be taken into consideration when posterior inlays of the types concerned are used. PMID- 1441937 TI - Team approach to tibial fracture. 37 consecutive type III cases reviewed after 2 10 years. AB - During a 10-year period, we managed 35 patients with 37 cases of Type III open tibial fractures, 15 cases within 1 week and 22 as late referrals. In all cases, simultaneous assessment and management by a microvascular and an orthopedic surgeon were mandatory throughout the treatment period. 6 of the 15 acute cases had a primary amputation. Of the remaining 31 cases, limb salvage was possible in 27. 31 flaps, pedicle and microvascular free flaps were used. Major complications occurred in 6 cases, but in 27 cases infection-free solid union was obtained. At long-term follow-up, average 5 years, the function was good or acceptable in 23 cases. We conclude that: (1) patients with Type III tibial injuries should preferably be transferred within a week after injury to a hospital where major reconstructive procedures are commonly performed, (2) early soft tissue coverage is essential in the management of these injuries, (3) unilateral external fixation should be the preferred technique of stabilization, and, finally, (4) plastic surgery expertise is important in management of severe tibial fractures. PMID- 1441938 TI - Free tissue transfer for type III tibial fractures. Microsurgery in 19 cases. AB - We report 19 tibial fractures Types III B and C treated by free flaps. The fracture healed in 16 cases after 12 (3-54) months. In 3 cases a secondary amputation was carried out. Tibial malalignment or substantial shortening ensued in 1 case each. We conclude that coverage with free flaps, radical removal of dead bone, stable external fixation and transfer of vascularized bone may salvage the majority of Type III B and C tibial fracture with function superior to that after amputation. PMID- 1441940 TI - Blood flow and mechanical properties of healing bone. Femoral osteotomies studied in rats. AB - In male Wistar rats, a transverse osteotomy at the midshaft of the femur was made, and the acute effects on bone flow were measured before and after reaming. Flow and mechanical variables in the healing bones were measured at 4, 8, and 12 weeks following osteotomy. Osteotomy reduced total bone blood flow by about 50 percent, and cortical flow in the diaphysis by approximately 40 percent. Cortical flow was equally diminished in the mid-diaphysis and in the osteotomy area, and no differences between the proximal and distal diaphyseal flows were found. Reaming of the osteotomized bones did not lead to any further flow reduction. At 4 weeks, total bone flow was more than doubled; increases were found in every segment of the fractured bone, and a more than 10-fold increase in the callus area was seen. At the end of the experiment, the femurs had regained 83 percent of their normal strength, 88 percent of normal rigidity and 78 percent of normal fracture energy. At this time total bone flow was marginally increased, flows in the proximal and the distal diaphyses were almost normalized, while a nearly 3 fold increase was still found in the callus area. Flow in the callus area gradually decreased during healing, and regression analysis demonstrated a negative correlation between callus flow and mechanical properties. PMID- 1441939 TI - Reconstruction of the Achilles tendon region by free microvascular flaps. 9 cases followed for 1-9 years. AB - In 1981-89, 9 patients underwent reconstruction for complex injuries in the Achilles tendon region. 10 free microvascular flaps were used: 5 fasciocutaneous and 5 muscle or musculocutaneous flaps. In addition, 4 Achilles tendons and 1 tibial posterior nerve were reconstructed, 1 femoropopliteal bypass was performed, and 6 tibial fractures were treated. The patients were re-examined on an average 3.5 years after the reconstruction. The stability of soft tissues was good in all patients. Good contour was achieved in superficial defects with fasciocutaneous and in deep injuries with latissimus dorsi free flaps. The calcaneal tendon function was good in 5, fair in 2 and poor in 2 patients, depending on the severity of the underlying skeletal injury. We conclude that free microvascular transfer offers one-stage reconstruction of complex, infected wounds in the Achilles tendon region, promotes fracture healing, and allows simultaneous tendon or nerve repair. PMID- 1441941 TI - Closed versus open medullary nailing of femoral fractures. Blood flow and healing studied in rats. AB - In rats, bilateral closed femoral fractures were produced. On the left side, closed intramedullary nailing was done, and on the right side, the nail was inserted by an open procedure. The healing process of the fractures was evaluated at 4, 8, and 12 weeks, bone and muscle blood flows were also determined. Reaming had no acute impact on bone blood flow, while reaming and fracture halved total bone flow (P < 0.04), and reduced cortical diaphyseal flow to approximately one quarter (P < 0.01). No differences were found between the open and closed methods. At 4 weeks, the bending moment, rigidity, and fracture energy of the fractures treated by closed medullary nailing were greater than those treated by open nailing. The fracture energy was still greater at 8 weeks, while no differences were seen in bending moment and rigidity. At 12 weeks, however, there were no differences in the mechanical parameters. Bone blood flows in both the cortical diaphysis and callus area were increased at 4 and in the callus area at 8 weeks in bones treated by the open method. No differences were found at the end of the experiment. Muscle blood flow was not different in the two limbs, and was constant during the experimental period. We conclude that femoral fractures treated by closed nailing heal better in the initial phase compared with those that have been openly nailed. This difference cannot be explained by an impaired muscle or bone blood flow due to open surgery. PMID- 1441942 TI - The radiographic classification of medial gonarthrosis. Correlation with operation methods in 200 knees. AB - Ahlback's classification of gonarthrosis can be applied with improved precision by careful interpretation of anteroposterior varus stress and lateral radiographs of the knee. The tibial lesion in early gonarthrosis is located in the anterior and middle part of the medial plateau. In more advanced disease, when the anterior cruciate ligament is invariably damaged, the lesion extends to the posterior margin of the medial tibial plateau. We studied the preoperative radiographs of 200 knees with arthrosis. We were able to predict the integrity of the anterior cruciate ligament (and the use of unicompartmental arthroplasty) with 95 percent accuracy and rupture or damage to the anterior cruciate ligament (and the use of total condylar arthroplasty) with 100 percent accuracy. We believe that the Ahlback classification reflects the anatomic and pathologic progression of medial compartment gonarthrosis, and is of value in allowing more accurate comparisons to be made of different methods of treatment. PMID- 1441944 TI - Collagen ultrastructure in ruptured cruciate ligaments. An electron microscopic investigation. AB - The ultrastructure of collagen fibrils was investigated in normal (n 39) and ruptured (n 23) human anterior cruciate ligaments. The normal ligament had a complex three-dimensional structure. Collagen fibrils predominantly had a undirectional course with parallel arrangement and a mean diameter of 75 (20-185) nm. Four days after anterior cruciate ligament rupture, the mean fibril diameter was increased; it later decreased, probably due to synthesis of young, thin 30-40 nm fibrils. Interfibrillar dysplastic collagen fibrils were detected in the extracellular matrix of ruptured ligaments. They were more frequently found later than 3 days after rupture and were seen also at a distance of 2-3 cm from the rupture zone. The presence of dysplastic fibrils may explain the functional insufficiency of the repair tissue in ruptured cruciate ligaments. PMID- 1441943 TI - Devascularization of the anterior cruciate ligament by synovial stripping in rabbits. An experimental model. AB - In rabbits, synovial stripping of the anterior cruciate ligament was performed, and histologic and mechanical changes were followed up to 2 months. The operation did not immediately affect the strength of the ligament or its histological structure. However, a gradual deterioration of mechanical properties, associated with collagen necrosis and an ineffectual reparative response, was evident. Thus, synovial stripping of the ligament with the attendant concomitant devascularization leads to ligamentary insufficiency despite the lack of structural damage to the ligament by the contusion itself. PMID- 1441945 TI - Arthrosis after surgically treated acetabular fractures. A retrospective study of 60 cases. AB - 59 patients with 60 surgically treated acetabular fractures were followed up to 25 years. Coxarthrosis developed within 3 years in 23 fractured hips. There was a high correlation between nonanatomic reduction and posttraumatic arthrosis. The long-term results after an acetabular fracture can be predicted within 2-3 years of surgery. PMID- 1441946 TI - The triradiate incision for acetabular fractures. A prospective study of 23 cases. AB - 24 acetabular fractures, displaced in the dome, were operated on through the triradiate incision, and 23 were followed for at least 2 years. All but one fracture were anatomically reduced in the dome. At follow-up, 7 hips had developed arthrosis, all with comminuted fractures with separate osteochondral dome fragments. Heterotopic bone formation occurred in 13 hips: 10/14 with indomethacin prophylaxis had no heterotopic bone, whereas all 9 without indomethacin prophylaxis had. We conclude that the triradiate incision is suitable for surgical treatment of complex acetabular fractures, and that the heterotopic bone formation can be reduced by indomethacin prophylaxis. PMID- 1441947 TI - Human growth hormone in polymethyl methacrylate. A controlled study of 15 hip arthroplasties. AB - Growth hormone-loaded polymethyl methacrylate (PMMA) was used in 15 hip replacements. The levels of growth hormone and insulin growth factor-I from the hip and the blood were measured before, and after, implanting PMMA containing 20 mg of growth hormone. Low levels of growth hormone and insulin growth factor-I were found in the femur initially, but very high local levels were found after implanting the growth hormone-loaded PMMA. These results were compared with the low levels found in 15 patients in a control group undergoing cemented or cementless hip replacement without added growth hormone. The local levels of growth hormone and insulin growth factor-I declined rapidly during the first 72 hours and were near normal at the end of this time. Systemic levels of growth hormone and insulin growth factor-I were not affected by the implantation of growth hormone-loaded PMMA. No complications or adverse reactions were noted. However, randomized studies with long-term follow-up are mandatory before the use of growth hormone-loaded PMMA is justified. PMID- 1441948 TI - Prognosis in Perthes' disease after noncontainment treatment. 106 hips followed for 28-47 years. AB - The results in 96 patients (106 hips) with Perthes' disease who had had conservative noncontainment treatment were studied after 35 (28-47) years. At skeletal maturity, the radiographic result was poor in 65 hips. At the average age of 43 years, radiographic signs of arthrosis were found in 48 patients (51 hips); 5 patients had had hip replacement and 13 patients had symptoms justifying that procedure. At early phases of the disease, radiographs showed biocompartmentalization of the acetabulum in 24 percent of the hips, but the acetabulum normalized in the majority. There was no difference in long-term prognosis between Catterall's Groups III and IV; two or more signs of head-at risk were not of prognostic value. The patients' age at diagnosis and the shape of the femoral head at skeletal maturity were the most reliable prognostic factors. PMID- 1441950 TI - Treatment of hip fracture in Finland and Sweden. Prospective comparison of 788 cases in three hospitals. AB - A prospective population-based study of hip fracture treatment was performed during 1989 in the regional hospitals of Oulu (Finland) and Sundsvall and Lund (Sweden). For cervical fractures hemiarthroplasty was preferred in Oulu and osteosynthesis in Sundsvall and Lund. For trochanteric fractures screw-plate was preferred in Oulu and Lund and Ender-nailing in Sundsvall. A shorter mean time at the orthopedic department in Oulu (13 days) was compensated by a lower (14 percent) fraction of patients directly discharged to own home. A somewhat longer mean orthopedic hospitalization time in Sundsvall (19 days) and Lund (17 days) was combined with a higher discharge to own home (49 percent and 35 percent). Prospective multicenter comparisons of treatment combinations (both operation and rehabilitation) permit identification of programs that are optimal for both patient and society. PMID- 1441949 TI - Effect of hyperbaric oxygenation on femoral head osteonecrosis in spontaneously hypertensive rats. AB - We investigated the effects of hyperbaric oxygenation (HBO) on ischemic osteonecrosis and on ossification disturbance of the femoral heads in growing, spontaneously hypertensive rats (SHR). 10 male SHRs aged 5 weeks (Group A) and another 10 male SHRs aged 8 weeks (Group B) were treated with HBO at 2.8 atmosphere absolute (ATA) for 6 weeks in a total of 30 hours. The control animals, 10 male SHRs (Group C) and 10 male wistar Kyoto rats (WKY, Group D), were kept under normal laboratory conditions. All the rats were killed at the age of 17 weeks for microscopic examination. In Group A, there was no evidence of osteonecrosis, and only 2 femoral heads with ossification disturbance were observed. In Group B, there were 2 femoral heads with osteonecrosis and 1 with ossification disturbance. In contrast, there were 6 femoral heads with osteonecrosis and 4 with ossification disturbance in Group C. It was concluded that HBO prevented osteonecrosis and ossification disturbance of the femoral heads in SHR. PMID- 1441951 TI - Hip arthroplasty in Jutland, Denmark. Age and sex-specific incidences of primary operations. AB - During the 10-year period 1981-90, 1752 primary total hip arthroplasties were performed in the County of South Jutland, Denmark. The annual number increased to a steady state during 1988-90. In this period, the incidence was highest in the age group 70-79 years for both women and men, with 485 and 410 arthroplasties per 100,000 inhabitants, respectively; the overall incidence was 82 per 100,000 inhabitants. During the next 30 years, the demand for primary hip arthroplasties in Denmark is expected to increase because of demographic changes. PMID- 1441952 TI - Renal function after hip arthroplasty and isoxazolylpenicillin prophylaxis. AB - Two different isoxazolylpenicillins (cloxacillin and dicloxacillin) were compared regarding impairment of renal function after total hip arthroplasty. 85 patients received dicloxacillin and 93 patients received cloxacillin as antibiotic prophylaxis. A total dose of 6 grams was given during a 36-hour period in doses of 1 gram pre-, per- and postoperatively. Creatinine in serum and beta 2 microglobulin in serum and urine were determined preoperatively and 2, 4, and 10 days after the operation. The dicloxacillin-treated patients had an increase in creatinine and beta 2-microglobulin in serum that was not seen in the cloxacillin group. The increase indicates a transient injury in the process of glomerular filtration. Although the increase was temporary and subclinical, a dose reduction is nevertheless recommended for older patients. PMID- 1441953 TI - Acetabular cement temperature in arthroplasty. Effect of water cooling in 19 cases. AB - In 19 patients who underwent total hip arthroplasty the temperature was studied at the bone-cement interface in the acetabulum during the polymethyl methacrylate curing process. To evaluate the effect of fluid cooling, the patients were randomized into two groups: one group with no irrigation, the other with continuous irrigation with Ringer solution during cement curing. The temperature was recorded with a thermocouple at the bone-cement interface. Without water cooling, the median maximum temperature was 49 (41-67) degrees C. In 9 out of 11 patients the temperature elevations were sufficient to cause impaired bone regeneration or thermal necrosis of bone. Continuous water irrigation reduced the amount of heat at the bone-cement interface; median maximum temperature was 41 (37-48) degrees C. PMID- 1441954 TI - Hyperthermia during occipito-cervical fusion with acrylic cement. Epidural thermometry in 23 cases. AB - In 22 patients, 23 posterior occipito-cervical fusions using acrylic cement were studied; 18 had seropositive rheumatoid arthritis and 4 traumatic atlanto-axial instability. The mean age was 60 (39-75) years. During the curing of the cement, epidural temperature measurements were performed over the cerebellum and between the foramen magnum and C1. Temperatures up to 69 degrees C were recorded. Cooling with profuse surface irrigation using normal saline solution or precooled 8 degrees C fluid did not influence the maximal temperatures recorded under the cement. Even though no gross neurological damage was noted, the epidural temperatures in occipito-cervical fusion with acrylic cement can be of sufficient degree to be hazardous; surface irrigation does not seem to be an effective way to reduce this risk. PMID- 1441955 TI - Cement removal in revision hip arthroplasty. Experience with bone cement added to the cavity in 20 cases. AB - A new technique for cement removal is presented where bone cement is added to the cavity after removal of a femoral component. The old and new segments of cement are then removed together by using a threaded extractor. In 16 of 20 patients, the method was successful; the entire cement mass was extracted in 35 (25-50) min without complications or bone loss. In 4 of the patients, the technique had to be combined with traditional methods for cement removal. PMID- 1441956 TI - Colles' fracture associated with reduced bone mineral content. Photon densitometry in 74 patients with matched controls. AB - In a prospective population-based investigation, we measured bone mineral density (BMD) of the forearm using single-photon absorptiometry at both a distal and a more proximal site in 74 Colles'-fracture patients who were compared with controls matched for age, sex, and years after menopause. For both groups there was a marked inverse relationship between age and bone mass. However, over the entire age range, the probands had 11 percent reduced BMD when compared with the controls. Our findings confirm that patients with fracture of the distal forearm have reduced BMD. They constitute an appropriate group for studies aimed at prevention of fracture in the elderly. PMID- 1441957 TI - Capitate-hamate fusion for Kienbock's disease. Good results in 8 cases followed for 3 years. AB - 8 patients with Kienbock's disease and without negative ulnar variance were treated with a modification of Chuinard's capitate-hamate fusion. All patients returned to their normal activities free of pain. The postoperative wrist motion was unchanged, but the grip strength was increased. PMID- 1441958 TI - Stress fracture in the medial femoral condyle. A case report. AB - An 88-year-old woman complained of pain in the medial part of her knee for 5 weeks. Plain radiography was normal. Clinical and scintigraphic findings were suggestive of spontaneous osteonecrosis of the medial femoral condyle. Magnetic resonance imaging showed a stress fracture of the medial femoral condyle. In 3 weeks pain had disappeared, confirming this diagnosis. PMID- 1441959 TI - Tissue expansion to cover amputation stumps. A case report. PMID- 1441960 TI - A case of intraosseous angioleiomyoma. AB - We report a rare case of expansively growing angioleiomyoma in the proximal tibia of a 64-year-old woman. MRI revealed a well-defined area of low signal intensity on T1-weighted image and high intensity on T2-weighted image. Angiographs showed hypervascularity and vascular poolings. Microscopic examination after incisional biopsy showed an angioleiomyoma with bundles of nerve fibers. PMID- 1441961 TI - [Experimental carpal displacement induced by ligamental lesions]. AB - Ligamentous lesions were created experimentally in 40 fresh cadaver wrists. The precise localization of traumatic rupture of the ligaments and the subsequent carpal imbalance were defined by the comparison between the experimental results and the clinical displacements. The displacements may be permanent, sequential or induced by external forces. Lesions of capsular ligaments cause the displacement. There are 3 functional units; the distal scaphoid complex; the palmar ligaments which form a "belt", consisting of the lateral external ligament, the radiocarpal ligaments an the radiate ligament; the medial ligaments, which also form a "belt" consisting of the palmar triquetral ligaments on each side of the triquetrum. The sprains are caused by a lesion of a functional unit. The lateral sprain is characterized by a lesion of the distal scaphoid complex. The scaphoid moves into a horizontal position, causing a dorsal deviation of the lunate and a scapholunate diastasis. The central sprain is induced by a rupture of the palmar "belt", causing an anteroposterior radiocarpal or mediocarpal drawer movement. The medial sprain is induced by the rupture, of different extents, of the medial ligaments. On examination, there is either a click or a palmar deviation of the lunate, sometimes with a lunotriquetral diastasis. The dislocations of the wrist are caused by lesion of several ligamentous units. PMID- 1441962 TI - Additional mechanical tests of bone cements. AB - A revision of the ISO-standard for bone cement testing has been proposed to include compressive strength after 24 hours in air and 4-point bending testing after 50 hours in a 37 degrees water bath. Nine commercially available bone cements were tested in accordance with the new program. Compressive strength varied from 78 to 100 MPa, bending strength from 48 to 74 MPa and bending modulus from 2.2 to 2.8 GPa. The highest strengths, but also the highest stiffness, were encountered with Simplex brands and low-viscosity cements. PMID- 1441963 TI - [Multidimensional analysis of reactive forces of the foot during normal walking]. AB - The authors present the analysis of the three components of ground reaction forces on both left and right feet on 50 subjects. Fourier analysis shows that a 25-Hz sampling is sufficient to fully characterize the normal gait. The approach used in order to study the data tables built for each component consisted in principal component factor analysis. This multivariate method, which looses the least possible information in relation to raw data, has indicated a high variability between subjects. Concerning the intrasubject variability, great asymmetry occurred between the forward and back forces. With respect to the relationship, the three components, the medial-lateral force was very independent of the two others. Particular classes of normal gait have been proposed. PMID- 1441964 TI - The development of discopathy in lumbar discs adjacent to a lumbar anterior interbody spondylodesis. A retrospective matched-pair study with a postoperative follow-up of 16 years. AB - Of 46 patients who underwent a lumbar or lumbo-sacral anterior interbody fusion at one or two levels, 16 were available for a follow-up of 16-20 years. The indications for operation were instability, degenerative disc disease, pseudarthrosis of a posterior fusion, and spondylolisthesis. Preoperative roentgenograms were compared with those made at follow-up 16 years (or more) later. In only a minority of patients was discopathy or instability found. The roentgenographic findings of the operated patients at a follow-up of at least 16 years were compared with those of a group of age- and sex-matched controls not previously treated for backache. We found that most degenerative changes of the adjacent discs occurred at a rate nearly similar to that in the corresponding levels of the controls. These results may suggest that lumbar anterior interbody spondylodesis does not accelerate the development of degenerative changes in adjacent discs. PMID- 1441965 TI - [Microradiography in the study of trabecular parameters]. AB - The intermethod variation in measurement of trabecular bone volume (VTO) and the indirect estimation of its microstructure according to Parfitt MTPT (microns), MTPD (/mm) and MTPS (microns) were evaluated in seven undecalcified bone biopsies by analyzing the microradiograph of a 100-microns-thick section with an automatic method (IBAS II Zeiss, Munich) in addition to reference methods (manual and semiautomatic) described in the literature and performed on 7-microns-thick stained sections. Three consecutive 7-microns-stained sections and one 100-mu thick microradiographed section were taken in each specimen. The 100 microns thick section was also superficially stained. Trabecular bone volume was measured with both a manual integrating eyepiece and an automatic method. The automatic method on the microradiograph underestimated the VTO by 24.42%. There was a correlation (r = 0.75; p < 0.02) between the manual and computerized methods. Mean trabecular plate thickness (microns), mean trabecular plate density (/mm) and mean trabecular separation (microns) were measured with both semiautomatic and automatic methods. The automatic method on the microradiograph underestimated the MTPT (microns) by 18.98% and the MTPD (/mm) by 14.14% and overestimated the MTPS (microns) by 23.17%. For the MTPT (microns) there was a correlation (r = 0.88; p < 0.02), between both methods, and the correlation was good for MTPD (/mm) (r = 0.97; p < 0.001), and MTPS (r = 0.86; p < 0.002). PMID- 1441966 TI - Retrosternal dislocation of the clavicle. AB - Retrosternal dislocation of the clavicle is an uncommon injury which may affect the mediastinal structures in a life-threatening way. Therefore, computed tomography is mandatory. Manipulation in the acute situation is the treatment of choice. In case of failure or old dislocation, open reduction with stabilization of the joint is required. The literature on this subject has been reviewed and an additional two cases are reported. PMID- 1441967 TI - [Compression neuropathy of the cubital nerve at the elbow]. AB - Compression neuropathy of the ulnar nerve at the elbow has numerous known etiologies, and the anatomy of the ulnar nerve around the elbow leaves it vulnerable to compression at numerous sites. The compression may be extrinsic such as in occupational neuropathy or in cases of postanesthesia neuropathy. The so-called idiopathic compression may be favored by some anatomic variations. The cubital tunnel retinaculum may be loose, leading to ulnar nerve dislocation or subluxation or tight compression of the nerve during flexion of the elbow. Bulging of the synovium in the floor of the tunnel may be the cause of compression in rheumatoid arthritis, whereas osteophytes may be the cause in degenerative osteoarthritis. Cubitus valgus or instability due to a pseudarthrosis of the lateral epicondyle or to ligamentous injury may stretch the nerve. The choice of a surgical technique must be based on (i) the pathophysiology of chronic nerve compression at the elbow, (ii) an understanding of the etiology of the nerve compression in the particular patient's case, and (iii) the knowledge of the potential technical drawbacks of the various operative procedures. Simple decompression is the first choice in case of minimal compression without instability of the nerve. Decompression of the nerve with a medial epicondylectomy is indicated in case of instability of the nerve and is the first choice in case of pseudarthrosis or malunion of the medial epicondyle. Ulnar nerve transposition is technically the most demanding procedure. Inadequate surgical technique creates new sites of compression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1441968 TI - Posterolateral bone grafting for nonunion of the tibia. AB - Sixty-two tibial diaphyseal nonunions in 60 patients were treated with a posterolateral bone graft over an 18-year period (1969-1987). The majority were complicated by severe soft tissue damage or segmental bone loss. Thirty-four had a deep infection. Primary healing was achieved in 92%. Three types of bone grafts have been used: from 1969 to 1978 either a whole iliac bone graft (10 tibiae) or a nonvascularized fibular graft (11 tibiae) was used. Since 1978 small iliac cancellous bone chips (41 remaining tibiae) were applied to the posterior surfaces of tibia and interosseous membrane. In three tibiae with major bone defects, cancellous allografts were added to the autogenous bone. The use of cortico-cancellous bone chips resulted in a shorter healing time, compared to a nonvascularized fibular graft or a massive corticocancellous bone block. PMID- 1441969 TI - [The treatment of rigid hallux using Swanson's silastic implant (single and double stem). Clinical, radiological and podobarographic review with a 16-year maximum follow-up]. AB - Twenty-eight cases of hallux rigidus treated with the Swanson Silastic implant (single and double stem) were reviewed, with an 8-year follow-up. The skin complication rate was significant. Long-term patient satisfaction was good. Radiologic findings were alarming: implants seem to wear out quickly on the articular side, and granulomatous reactions develop around the stems. Dynamic pedobarography shows decreased pressure under the first ray, with transfer of the weight to the midmetatarsal heads, sometimes on the external edge of the foot. The authors review the international literature on the etiology, pathology and treatment of hallux rigidus. Surgical indications and techniques are specified. PMID- 1441971 TI - Osteosynthesis of pathologic fractures and prophylactic internal fixation of metastases in long bones. AB - Osteosynthesis was performed in 36 pathologic fractures, and in 21 metastases prophylactic internal fixation was carried out. The principles of the operative technique consist of a rigid osteosynthesis with removal of metastatic tissue and filling up of the bone defect with allograft or methylmethacrylate. The indications and benefits of prophylactic internal fixation are discussed. PMID- 1441970 TI - Rational therapy for ingrown toenails. A prospective study. AB - Partial phenolization of the germinal matrix is described as a simple and effective procedure for the treatment of ingrown toenails. It is illustrated in a summary of anatomy and pathophysiology as well as in a randomized prospective trial. PMID- 1441972 TI - Intrapelvic intrusion of the lumbosacral spine. AB - A 34-year-old female fell 7 meters onto her lower back and side, and sustained a nondislocated fracture of the 7th thoracic vertebra, a complex pelvic fracture with symphysiolysis and a left acetabular fracture in combination with a bilateral comminuted sacral fracture and downward intrusion of the lumbosacral spine. There was also a cauda equina-syndrome. Laparotomy with exploration of the lumbosacral area was terminated early because of hemorrhage. Later internal fixation of the fractures was performed by an anterior approach with complete reduction of the bilateral sacral fracture and the lumbosacral spine intrusion. We conclude that an anterior approach to this area gives good visualization, but is hazardous owing to the close proximity of the fractures to the central vessels and retroperitoneal muscles. A posterior approach gives less good visualization but may cause less hemorrhage. PMID- 1441973 TI - A patient with two upper lumbar disc herniations. AB - Of all lumbar disc herniations, less than 5% occur in the upper lumbar area. Though protrusions are common at all levels, truly extruded disc herniations in the upper lumbar area from L1 to L3 are rare. Even more unusual is the multilevel occurrence of herniations in this area. The authors stress the importance of accurate diagnosis and clinically directed medical imaging work-ups. PMID- 1441974 TI - Dorsolumbar spine duplication. AB - We report a case of dorsolumbar spine duplication in a female patient. She had several vertebral anomalies, such as fused vertebrae, hemivertebrae and butterfly vertebrae, together with duplication of the spinal column in the lower thoracic and the whole lumbar tract. Clinically, she had no control of the sphincters, but her gait was only slightly affected. This is probably the third reported case of this rare anomaly. PMID- 1441975 TI - Chondromatosis of the fifth metacarpophalangeal joint. Case report and review of the literature. AB - Synovial chondromatosis is extremely rare in small joints. The authors present a case of involvement of the fifth metacarpophalangeal joint, treated by removal of loose bodies and synovectomy. PMID- 1441976 TI - Double-level spinal injury resulting in "en bloc" dislocation of the lumbar spine. A case report. AB - We report the case of a 21-year-old man with a unilateral lumbosacral dislocation together with a fracture of L1 resulting in "en bloc" dislocation, which is difficult to classify from an anatomopathological and biomechanical point of view. Unilateral lumbosacral dislocation is likewise an infrequent injury with less than 10 cases previously reported. Its association results in an anterior displacement to the left of the whole lumbar spine. To our knowledge, this displacement "en bloc" of the lumbar spine represents a rotatory dislocation of the same, an injury which we have not seen described until now in the literature. PMID- 1441977 TI - Patellar fracture in a patient with Forestier's disease. PMID- 1441978 TI - Ulnar approach to the wrist. AB - An ulnar approach to the wrist is described. We used this technique for several reconstructive procedures in more than 30 cases. PMID- 1441979 TI - A surgical approach for the repair of large tears of the rotator cuff. PMID- 1441980 TI - Advantages of the enlarged middle cranial fossa approach in acoustic neurinoma surgery. A review. AB - Utilizing an enlarged middle cranial fossa approach to the cerebello-pontine angle without destruction of the labyrinth or cochlea the authors have since 1981 operated on 263 unilateral acoustic neurinomas. Tumour sizes ranged between 3 mm intrameatal and 35 mm within the cerebello-pontine angle. Complete tumour removal was accomplished in 96%. There was one postoperative mortality, and only rarely neurological complications. Excellent function of the facial nerve was obtained in 78% (in small and medium sized neurinomas 90% House I and II) and severe paralysis persisted in only 6%. Preservation of hearing was possible in 70% of the small tumours, and in 50% of the total group. Against this background comparable data of the literature are reviewed, and the indications for the enlarged midfossa approach analyzed. PMID- 1441981 TI - Initiation of sinusoidal tracking eye movements in man. AB - Smooth pursuit eye movement was recorded with a DC amplifier during horizontal sinusoidal target motion at 0.3, 0.6, 0.8, 1.0 and 1.2 Hz and a peak-to-peak amplitude of 20 degrees. Eye movement was digitalized at 100 Hz and 12 bits. From the digitalized eye movements, the maximum position error, the correlation coefficient and regression coefficients between stimulus and eye position were calculated in each half cycle. The A/D conversion and calculation were performed using a 16 bit microcomputer (NEC PC 98). Thirteen healthy volunteers with normal smooth pursuit patterns were examined. The correlation coefficient increased, but the maximum position error and the two regression coefficients decreased as the target moved. However, all four stabilized from about the 3rd half cycle regardless of the target frequency. These findings indicate that the smooth pursuit of a sinusoidally moving target reaches the maintenance at about the 3rd half cycle after initiation of two half cycles from the beginning of the target motion. This might be due to a prediction (or learning) of periodicity. PMID- 1441983 TI - Retinal ganglion cells related to optokinetic nystagmus in the rat. AB - The nucleus of the optic tract (NOT) in the pretectum is the visuo-motor relay between the retina and preoculomotor structure in the pathway conveying signals responsible for optokinetic nystagmus (OKN) in both afoveate and foveate animals. Unilateral lesions of the NOT abolish OKN toward the side ipsilateral to the lesion. However, what parts of the retina and what kinds of retinal ganglion cells project their fibers into the NOT are still unknown. To examine this, horseradish peroxidase conjugated with wheatgerm agglutinin was injected into the NOT of the rat. Labeled retinal ganglion cells were diffusely documented in the contralateral side, whereas those situated only in the lower temporal crescent, were found in the ipsilateral side. Ganglion cells dominated in the range of small cells, i.e., W cells. Therefore, ganglion cells responsible for OKN are believed to be related to W cells. However, medium-sized and large cells were definitely labeled in the rat, suggesting possible participation of these cells in OKN. PMID- 1441982 TI - Plasticity of the human otolith-ocular reflex. AB - The eye movement response to earth vertical axis rotation in the dark, a semicircular canal stimulus, can be altered by prior exposure to combined visual vestibular stimuli. Such plasticity of the vestibulo-ocular reflex has not been described for earth horizontal axis rotation, a dynamic otolith stimulus. Twenty normal human subjects underwent one of two types of adaptation paradigms designed either to attenuate or enhance the gain of the semicircular canal-ocular reflex prior to undergoing otolith-ocular reflex testing with horizontal axis rotation. The adaptation paradigm paired a 0.2 Hz sinusoidal rotation about a vertical axis with a 0.2 Hz optokinetic stripe pattern that was deliberately mismatched in peak velocity. Pre- and post-adaptation horizontal axis rotations were at 60 degrees/s in the dark and produced a modulation in the slow component velocity of nystagmus having a frequency of 0.17 Hz due to putative stimulation of the otolith organs. Results showed that the magnitude of this modulation component response was altered in a manner similar to the alteration in semicircular canal-ocular responses. These results suggest that physiologic alteration of the vestibulo ocular reflex using deliberately mismatched visual and semicircular canal stimuli induces changes in both canal-ocular and otolith-ocular responses. We postulate, therefore, that central nervous system pathways responsible for controlling the gains of canal-ocular and otolith-ocular reflexes are shared. PMID- 1441984 TI - Phase audiometry in neuroaudiological practice. AB - Six groups of subjects, altogether 107 in number, were studied with phase audiometry. Three control groups were studied (normal-hearing healthy controls, persons with cochlear hearing losses, and patients with neurological disease not affecting the auditory system), and three patient groups were studied (patients with cerebellopontine angle tumours, with brainstem lesions, and with temporal lobe lesions). Two phase audiometers were used. The sensitivity was 85% for patients with cerebellopontine angle tumours, 71% for patients with brainstem lesions, and 69% for patients with temporal lobe lesions. There was good agreement between the phase audiometers, though one of them (BIAB Phase Audiometer) had better results for two of the patient groups. Phase audiometry can be recommended in neuroaudiological practice. PMID- 1441985 TI - Threshold shift, hair cell loss, and hair bundle stiffness following exposure to 120 and 125 dB pure tones in the neonatal chick. AB - One-day old chicks were exposed to one of two pure tone stimuli (0.9 kHz at 120 or 125 dB SPL) for 48 h. Three major results arose from a variety of tests that assessed the structural and functional consequences of the exposure on the peripheral auditory system at either 0 days or 12 to 15 days recovery. First, brainstem response data showed that the 120 and 125 dB groups had maximum evoked potential threshold shifts of 57 and 71 dB immediately after removal from the sound. Fifteen days post-exposure, the thresholds in the 120 dB group returned to near-normal levels, while in the 125 dB group, recovery was within 19 dB of control thresholds. Second, scanning electron microscopic measurements of hair cell density within the lesion showed that at 0 days recovery, the 120 and 125 dB groups had a 30% and 59% short hair cell loss, respectively, but by 15 days no differences could be identified between the exposed and control animals, regardless of exposure level. Finally, at 0 days of recovery, micromechanical stimulation data did not reveal any significant difference in stiffness between the control and surviving hair cells in the lesion area. Although the more intense exposure induced greater structural and functional damage in the chick cochlea, the birds retained or even enhanced their ability to replace lost hair cells and had partial hearing recovery by 15 days post-exposure. PMID- 1441986 TI - Permanent, skin penetrating, bone-anchored titanium implants. A clinical study of host-reaction in bone and soft tissue. AB - In 12 patients with a skin penetrating retroauricular titanium-implant (Branemark) the reaction in bone and soft tissue was studied. Observation time was 6 to 36 months. All implants were "osseointegrated", as assessed by repeated manual test, X-ray examination and 99mTC-scintigraphy. Soft tissue reactions appeared to be slight and clinically insignificant. However, all patients produced crusts around the abutment. When the abutment was removed varying degrees of inflammatory reaction in the skin penetration could be observed in most patients. A theory for the development and cause of the soft tissue reactions is proposed and changes in the operative procedure and the design of the abutment to reduce the host reaction are suggested. It is stressed that the clinical significance of this host reaction is uncertain and above all has to be weighed against the important benefits this implant system offers to a severely handicapped group of patients. PMID- 1441987 TI - Distribution of bone remodeling units in the otic capsule of the rabbit. A semiquantitative morphometric study. AB - Distribution of bone remodeling units (BRU) in relation to the perilymphatic space was studied in undecalcified temporal bones from adult rabbits labeled in vivo with bone-seeking fluorochromes. Based on recordings of focal bone formation, relative densities of BRUs inside concentric tissue zones around the inner ear spaces were estimated. Zonal densities of BRUs were found to decline towards the perilymphatic space, lending further support to the existence of a local inner ear mechanism in control of capsular bone tissue dynamics. The possible nature of this mechanism is considered briefly with special reference to inner ear electromechanic activity. PMID- 1441988 TI - Development of endolymphatic hydrops following immune response in the endolymphatic sac of the guinea pig. AB - The present study investigated immune injury associated with endolymphatic hydrops (e.hydrops) following locally mounted immune reaction in the endolymphatic sac (e.sac) of guinea pigs. E.hydrops occurred, progressing rapidly within the first week post secondary Keyhole limpet hemocyanin (KLH) challenge in the e.sac and developed into two phases, acute and chronic. On the other hand, primary KLH challenge of the e.sac, PBS inoculation into the e.sac or intradural secondary KLH challenge were incapable of inducing e.hydrops. These results indicate that reversible and irreversible e.hydrops are induced by the immune response of the e.sac, suggesting that local immunological events of the e.sac may provide an animal model of Meniere's disease. PMID- 1441989 TI - Dark cell pathology in Meniere's disease. AB - The dark cells in the cristae of the semicircular canals were studied histopathologically in 9 temporal bones from individuals with Meniere's disease (MD group), 7 temporal bones with endolymphatic hydrops from individuals without a history of Meniere's disease (non-MD hydrops group), and 10 normal temporal bones (control group). The density of the dark cells was significantly lower in specimens in the MD group versus the non-MD hydrops group (Wilcoxon's ranking test, t = 90.5, p less than 0.01) and control group (Wilcoxon's ranking test, t = 50.0, p less than 0.01), and many of the dark cells were found to be abnormal in the specimens from the MD group. The difference in dark cell density between the non-MD hydrops group and control group, however, was not significant (Wilcoxon's ranking test, t = 75.0), and few cells in these groups were abnormal. It is speculated that the differences in density and the abnormalities in dark cell morphology might be either factors in the etiology of endolymphatic hydrops or results of Meniere's disease. Other, unknown, factors must be postulated to produce endolymphatic hydrops in ears with hydrops but without MD. PMID- 1441990 TI - Central projections from singular parts of the vestibular labyrinth in the guinea pig. AB - Primary afferent projections from singular parts of the vestibular labyrinth were studied in the guinea pig. The posterior ampullary nerve, the common trunk of the anterior and lateral ampullary nerves, as well as fibers innervating the macula sacculi or the macula utriculi were traced with crystals of horseradish peroxidase (HRP) lyophilisate. Posterior, as well as anterior and lateral ampullary fibers were found to project extensively to the superior vestibular nucleus, but also reached the other main vestibular nuclei. Saccular fibers projected mainly to the lateral parts of the lateral vestibular nucleus and to the adjoining descending and superior vestibular nuclei as well as to group y. Modest projections could be followed to the medial vestibular nucleus. Furthermore, a distinct saccular projection to the cochlear nuclei was evident. Utricular projections reached the four main vestibular nuclei with a denser accumulation of fibers within ventral parts of the lateral, descending and superior vestibular nuclei. PMID- 1441991 TI - The embryologic development of the human external auditory meatus. Preliminary report. AB - During the final period of embryogenesis, a funnel-shaped tube continues medially into the mesenchymal tissue forming a curved path. Although this may sound simple, the development occurring during early fetal life is in fact very complex. At first, ectodermal cells proliferate to fill the lumen of the meatus, forming the meatal plug, and then at 10 weeks the bottom of the plug extends in a disc-like fashion, so that in the horizontal plane the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. At the same time, the plug in the proximal portion of the neck starts to be resorbed. In the 13-week fetus, the disc-like plug begins to show signs of its final destiny; the innermost surface of the plug in contact with the anlage of the malleus is ready to contribute to the formation of the tympanic membrane. In the 15-week fetus, the innermost portion of the disc-like plug splits, leaving a thin ectodermal cell layer of immature tympanic membrane. The neck of the boot forms the border between the primary and secondary meatus, and is the last part to split. In the 16.5-week fetus, the meatus is fully patent throughout its entire length, although the lumen is still narrow and curved. In the 18-week fetus, the meatus is already fully expanded to its complete form. PMID- 1441992 TI - Otitis media with effusion: components which contribute to the viscous properties. AB - Middle ear effusions from children undergoing myringotomy were classified into thick (mucoid) and thin (serous) on the basis of their flow properties. Their composition was analysed and their rheological properties measured. The viscosity of the effusions was measured using a Contraves low shear viscometer and expressed as specific viscosity per mg/ml of non-dialysable solids present. In order to measure the effusion viscosity it was necessary to solubilize the effusion by mild homogenisation in a phosphate buffer pH 6.7 containing a cocktail of proteolytic inhibitors. The viscosity of mucoid effusions was significantly greater than that of the serous effusions. There was a small but measurable amount of proteolytic activity in the effusions, range 0.05-1.79 micrograms/mg of non-dialysable solids. This proteolytic activity was not significantly different between the thick and thin effusions and was therefore unlikely to explain the difference in viscosity. Analysis of the constituents of the effusions showed that glycoprotein and DNA but not protein nor lipid were significantly higher in the mucoid effusions compared to the serous effusions. The viscosity of the effusions correlated with the glycoprotein concentration but not with the protein or lipid concentration. Under certain circumstances the DNA concentration did correlate with the viscosity of the effusion. However, digestion with a proteinase free DNase did not reduce the viscosity of the effusion. These results demonstrate that classifying effusions as thick and thin based on visual inspection and flow properties is valid and that the only constituent present in the effusions that determines viscosity is mucin. PMID- 1441993 TI - Incidence and progression of myringo-incudo-pexy after secretory otitis. AB - A cohort of originally 327 healthy children born in 1975 was followed by repeated otomicroscopies and tympanometries from age 5 to age 16 years, in total 9 otomicroscopies. Prevalence of drum pathology, especially myringo-incudo-pexy was investigated. Prevalence of myringo-incudo-pexy was 0.5% at age 5 years, 2.5% at age 7 and 4.2% at age 16. Forty percent of pexies were stable; 36% fluctuated and 26% disappeared. Hearing was surprisingly good at age 16, but the pexy represents a risk for progression. PMID- 1441994 TI - Occurrence of antibodies to pneumococcal protein antigens in experimental acute otitis media. AB - To study serological antibody response to pneumococcal protein antigens, experimental pneumococcal (type 3) acute otitis media (AOM) was induced in 6 rats, sera being analysed with the Western blot technique at different intervals after bacterial challenge. The most striking finding was a distinct antibody response to a protein of about 35 kDa visible in 5 of the rat sera within 14 days, and persisting throughout the remainder of the study (i.e., 56 days in all). Moreover, appear to be a phenomenon restricted to type 3 pneumococci. Both the pathogenetic importance of this protein and the immunological response it evokes are still unclear. However, as antibodies to protein antigens may contribute to inflammatory reactions in the middle ear (e.g., otitis media with effusion), this 35-kDa protein might be important for the development of sequelae to AOM. PMID- 1441995 TI - Permeability of the normal round window membrane to Haemophilus influenzae type b endotoxin. AB - Sensorineural hearing loss associated with otitis media may be due to passage of ototoxic substances such as bacterial toxins and antibiotics, from the middle ear into the inner ear. The round window membrane is the most likely route for such transport. The aim of this study was to analyze the extent of endotoxin passage through the normal round window membrane. The round window membranes of 19 chinchillas were exposed in vivo to Gelfoam soaked in purified Haemophilus influenzae type b endotoxin at a concentration of 45,000 endotoxin units per ml (EU/ml) during 3 to 24 h. Endotoxin levels in the perilymph were measured with Limulus Amaebocyte Lysate or Quantitative Chromogenic Limulus Amaebocyte Lysate. Endotoxin was detected in half of the inner ears at concentrations close to the detection limit (approximately 4 EU/ml). The results suggest that the normal round window membrane efficiently protects the inner ear against the passage of bacterial endotoxins from the middle ear cavity. It is unlikely that endotoxin at concentrations found in the middle ear secretion during otitis media can traverse the round window membrane in sufficient amount to cause inner ear deterioration. PMID- 1441996 TI - Nasopharyngeal bacterial flora in otitis prone children treated with immunoglobulin. AB - The present study was undertaken to evaluate possible beneficial effects of regularly given, long term immunoglobulin prophylaxis of children below 2 years of age with recurrent acute otitis media (RAOM). The nasopharyngeal bacterial flora and the frequency of acute otitis media (AOM) and secretory otitis media SOM were studied. Every second of 44 children with 3 or more periods of AOM during the last year received immunoglobulin intramuscularly (Gammaglobulin Kabi 165 mg/l, 0.45 ml/kg b.w.) every third week for 6 months, while the other 22 children served as controls. All children were followed for 12 months. Immunoglobulin prophylaxis neither influenced the nasopharyngeal flora, nor the frequency of AOM or SOM periods. Children with AOM or SOM more often harbored bacterial pathogens in their nasopharynx than children with normal middle ear status. Also, the immunoglobulin prophylaxis did not influence the increased frequency of bacterial pathogens in the nasopharynx of children attending public day care or family day care as compared to those taken care of at home. PMID- 1441997 TI - Antigen reduces nasal transepithelial electric potential differences and alters ion transport in allergic rhinitis in vivo. AB - The change of ion transport in acute allergic reactions in vivo was studied by measuring the nasal transepithelial potential difference (PD) in patients with nasal allergy to Japanese cedar pollens. Comparison of nasal PD in the pollen season revealed a lower PD in the allergic patients than in the normal control subjects. We challenged the patients with allergen in the non-pollen season and measured the time course change of nasal PD and rate of inhibition of PD by amiloride and indomethacin. Nasal PD reached the lowest value 15 min after nasal allergen challenge. Percent inhibition of PD by amiloride was greater without the allergen challenge than it was in those patients after allergen challenge (51.7% versus 29.4%, p less than 0.01). Indomethacin did not change PD without allergen challenge, whereas it depressed nasal PD by 25.1% after allergen challenge. These results suggest that decreased sodium absorption and increased chloride secretion occur in local allergic reactions. Both changes may contribute to the increase in fluid transport towards the lumen, and this may lead to abnormalities of nasal secretion during acute allergic reactions. PMID- 1441998 TI - Mechanical properties of the vocal fold. Stress-strain studies. AB - The viscoelasticity of the vocal and ventricular folds was experimentally assessed by analyzing the stress-strain relationships obtained using a newly developed measuring system. The degree of stiffness of the mid-membranous portion of the vocal fold was less than that near the anterior commissure or the vocal process. The ventricular fold was much less stiff and significantly more viscous than the vocal fold. At the membranous portion of the vocal fold, the degree of stiffness was less and that of viscosity greater at 2 mm above and below the free margin than at the free margin itself. PMID- 1442000 TI - Thermal effects on the vestibular hair cell synapse have to be considered for the explanation of caloric nystagmus. PMID- 1441999 TI - Effects of folinic acid on 5-fluorouracil induced cell lethality with or without cisplatin against head and neck laryngeal squamous carcinoma multicellular tumor spheroids. AB - We evaluated the efficacy of folinic acid (Leucovorin, LV) on cell lethality induced by 5-fluorouracil (FU) alone or in combination with cisplatin (DDP) by using the HEp-2 laryngeal squamous carcinoma multicellular tumor spheroids (MTS) system. For LV, non-toxic concentration of 10(-5) M was used. For cells in the monolayer, 6 and 24 h exposure to LV increased FU-induced cell lethality approximately 7- and 2-fold, respectively, whereas LV did not influence the effect of FU for MTS. LV's lack of effect on cells in MTS may be interpreted to mean that LV cannot penetrate the MTS. For the monolayer, simultaneous exposure to 3 drugs, DDP, FU and LV, produced synergistic interaction. However, sequential exposures were marginally synergistic or antagonistic, irrespective of sequence of DDP first or last. In contrast, DDP followed by FU plus LV was most synergistic for MTS. Simultaneous exposure was also synergistic, however, FU plus LV followed by DDP was antagonistic. These results suggest that LV is unable to penetrate into the MTS core to potentiate FU activity. DDP appears to have enhanced LV penetration into the MTS core. The exploration of means to overcome limited penetration of LV appears important for successful treatment of head and neck carcinoma. PMID- 1442001 TI - Effect of intravenous diazepam and thiopental on voluntary saccades and pursuit eye movements. AB - The effects of diazepam and thiopental on voluntary saccades and pursuit eye movements were tested in 9 volunteers, with an interval of at least 2 weeks between tests. One, 4 and 8 h after intravenous injection of diazepam (0.3 mg/kg) or thiopental (6.0 mg/kg), voluntary saccades and pursuit eye movements were tested and blood samples taken for analysis of drug concentration. As compared to results of tests without drugs, a significant reduction both of saccadic peak velocity and gain of pursuit eye movements was found 1 h after injection of either drug, but not after 4 and 8 h. The amplitude of saccades elicited with the 60 degrees stimulus was significantly reduced 1 h after injection of diazepam. Latency of saccades increased significantly up to 4 h after injection of either drug. No significant correlation was found between peak velocity of saccades and blood concentration of either thiopental or diazepam 1 h after administration. The present results confirm that in man saccades and pursuit eye movements are reduced by benzodiazepines and barbiturates, but provide no support for the previously described efficacy of saccades in monitoring the effect of benzodiazepines. It is hypothesized that diazepam and thiopental also induce reduction of voluntary saccades and pursuit eye movements via a general sedation of the central nervous system (CNS), besides having specific effects on CNS structures important to the performance of voluntary eye movements. PMID- 1442002 TI - Plastic properties of the vestibulo-ocular reflex in olivo-ponto-cerebellar atrophy. AB - Disorders in vestibulo-ocular functions were studied in 4 patients with olivo ponto-cerebellar atrophy (OPCA). The phenomenon of habituation, considered as a plastic property of the vestibulo-ocular reflex (VOR), was explored with a behavioural paradigm in these patients. When subjected to the habituation paradigm all patients presented a modified response opposite to that observed in normal subjects. The role played by the cerebellum in relation to VOR plasticity- well known in different experimental models--is analyzed. The hypothesis of a modification of the cerebellum's inhibitory action on vestibular nuclei neurons is put forward to explain the inversion of the VOR habituation phenomenon in these patients. PMID- 1442003 TI - Effect of transcutaneous electrostimulation on noise-induced temporary threshold shift. AB - The effect of transcutaneous electrostimulation around the ear before and during noise exposure on noise-induced temporary threshold shift (TTS) was examined in 26 volunteers. Electrostimulation reduced TTS in the majority of cases and the reduction was statistically significant. Two possible mechanisms for this reduction are proposed: stimulation of the olivocochlear bundle and alteration of cochlear blood flow. Transcutaneous electrostimulation may be useful for prevention or treatment of noise induced hearing damage and for treatment of tinnitus. PMID- 1442004 TI - Noise-induced auditory loss: influence of genotype, naloxone and methyl prednisolone. AB - Inbred strains of mice have several advantages as models for human noise-induced hearing loss. However, the isogenic nature of inbred lines is very unlike the human condition, and may make this species less valuable as an auditory model. The present experiments start with two mouse genotypes having lifelong normal cochlear functions: The CBA/CaJ and the AUS/sJ inbred strains. These strains and their F1 hybrid offspring were examined for noise-induced elevation of the auditory brainstem response (ABR) threshold. The F1 line had an intermediate degree of loss and the most uniform high frequency cochlear loss. Methylprednisolone was found to protect the F1 from noise-induced losses, whereas naloxone did not. PMID- 1442005 TI - Immunohistochemical localization of alpha-atrial natriuretic polypeptide in the rat cochlea. AB - The localization of alpha-atrial natriuretic polypeptide (alpha-ANP) in the rat cochlea was studied by immunohistochemical technique, using a polyclonal antibody against synthetic rat alpha-atrial natriuretic polypeptide (alpha-rANP). The spiral ligament of the lateral cochlear wall exhibited pronounced immunoreactivity to atrial natriuretic polypeptide (ANP), whereas the stria vascularis displayed almost no immunoreaction. ANP immunoreactivity (IR) was also intense in the spiral limbus region. IR was observed in the fibroblast-like cells and in the extracellular matrix, in particular along its fibrous bundles, of both the spiral ligament and the spiral limbus. These results indicate that ANP may participate in the regulation of the water electrolyte balance at these sites, which may imply a role for ANP in the regulation of cochlear fluids. PMID- 1442006 TI - Localization of type II, IX and V collagen in the inner ear. AB - Types II and IX collagen are traditionally considered cartilage collagens; however, within the inner ear, types II and IX collagen have a more diverse distribution. In the adult gerbil, type II collagen is the major fibrillar component. In the otic capsule it is present surrounding the osteocytes embedded and branching in the periosteal layer, in the cartilaginous rests of the enchondral layer, and in the endosteal layer bordering the membranous labyrinth. In the regions of the sensory cells, type II collagen is found in the osseous spiral lamina, the connective tissue of the spiral limbus, the subepithelial tissue of the maculae in the vestibule and the cristae in the ampullae, and in the spiral ligament. It is present in the non-cartilaginous and acellular structures of the tectorial membrane over the cochlear hair cells and the vestibular membrane lining the semicircular canals. Type IX collagen, when present, in all cases co-localizes with type II collagen but is found in more limited regions. It is found only in the cartilaginous rests of the enchondral bone, the tectorial membrane and the vestibular membrane. Type V-like collagen, a connective tissue collagen, is found to have a complementary localization to types II and IX collagen within the interstitial bone of the otic capsule, the osseous spiral lamina and the tectorial membrane, but it is absent from the vestibular membrane. This report is the first documenting the co-localization of types II and IX collagen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442007 TI - Human embryonic organ of Corti in tissue culture and NSE expression. AB - For the first time ever, the cochlear tissue of the human embryo has been successfully grown in vitro in two cases, and neuro-specific enolase (NSE) immunoreactivity was studied in one of these tissues. The outer hair cells were arranged in three rows, and the inner hair cells in one row and in better order than the outer hair cells. After NSE immunostaining, the outer spiral bundle, tunnel fiber, outer hair cells, inner hair cells, and the spiral ganglion cells showed positive staining. This data suggests that the human embryonic cochlea has nearly reached complete maturation by 16 weeks, and that the tissue of the Corti organ can be differentiated and matured in vitro. PMID- 1442008 TI - Ultrastructural findings in the inner ear of Jackson shaker mice. AB - The ultrastructural characteristics of the inner ear of Jackson shaker mice were analyzed. We used 12 Jackson shaker mutants (js/js) with ages ranging from 10 to 47 days and 10 heterozygotes of the Jackson shaker (js/+) with ages ranging from 10 to 30 days. The most striking findings observed were incomplete differentiation of the stereocilia of the outer hair cells and the maculae, although outer and macular hair cell cytoplasm, including the nerve terminals, became fully developed. Most outer hair cells did not show regular W-shaped configuration of the stereocilia throughout the entire turns of the cochlea except for a few hair cells. In many hair cells of the utricular and saccular maculae, the classical pipe organ configuration of the stereocilia was not observed. The Jackson shaker mice have been reported to have a gene abnormality on chromosome 11, and its gene locus was close to that of our new-mutant mice which showed deranged stereocilia of the outer and macular hair cells. Therefore, future studies can provide additional information on the cytodifferentiation of the stereocilia as a function of the gene on chromosome 11. PMID- 1442009 TI - Expression of glycoconjugates in the human fetal cochlea. AB - The distribution of glycoconjugates in the human fetal cochlea was analyzed using six biotinylated lectins: wheat germ agglutinin (WGA), abrus precatorius agglutinin (APA), ulex europaeus agglutinin I (UEA-I), ricinus communis agglutinin 120 (RCA120), helix pomatia agglutinin (HPA), concanavalin A (ConA). The tectorial membrane (TM) in the 11- and 15-week-old human fetuses was labelled with WGA, APA, RCA120 and ConA, but not with UEA-I and HPA. In the 19-week-old fetuses, the reaction of the TM decreased. In the 11-, 15- and 19-week-old fetuses, the surface of the greater and the lesser epithelial ridges were respectively labelled with WGA, APA and RCA120. Reissner's membrane was labelled with WGA, ConA, APA, RCA120 and HPA. WGA, RCA120 and APA strongly stained the stria vascularis, especially in the 15-week-old fetuses. HPA did not stain the 11 week-old fetal cochleas at all, while it stained the apical surface of the hair cells, Reissner's membrane, the cells within the stria vascularis and spiral osseous lamina in the 15-week-old fetuses. In the 19-week-old fetuses, the fluorescent reaction with HPA became decreased and the apical surface of the hair cells was not labelled with HPA at all. This result suggests that HPA reactive glycoconjugates may be related to the molecule responsible for stereociliary adhesion only during development. PMID- 1442010 TI - Differences in hair bundles associated with type I and type II vestibular hair cells of the guinea pig saccule. AB - Several studies have reported variations in shape and size of stereociliary bundles and in a limited number of observations have associated them to type I and type II hair cells. A systematic study has been undertaken for which a technique was developed in order to identify both cell types and their corresponding hair bundles. Numerous fissures were obtained in saccular epithelia and observed in scanning electron microscopy. Saccular type I and type II hair cells in the guinea pig were found to have distinctive hair bundles. The tallest stereocilia of almost all type I cells were longer than 6 microns, and were shorter in the striola compared to the periphery. In contrast, the tallest stereocilia of almost all type II cells were shorter than 6 microns and were not found to vary notably in size from the striola to the periphery. Hair bundles with stereocilia organized in straight or in staggered rows were found for both types of cells across the whole saccular epithelium, with no apparent particular distribution. Possible physiological significance of differences in hair bundles is discussed. PMID- 1442011 TI - Periductal vessels of the endolymphatic duct. AB - Light microscope was used to examine the rich vascular plexus surrounding the human endolymphatic duct, both in the periductal loose connective tissue and in the bony channels surrounding the bony vestibular aqueduct. We also performed computer-aided three-dimensional reconstruction on one serially sectioned region of the endolymphatic duct. We found an anastomotic and looping network of vessels residing in the loose connective tissue close to the epithelium of the endolymphatic duct. This network often received a vascular contribution from the vessels in the periaqueductal bony channels. These findings were verified by light microscopic examination of 50 temporal bone specimens. Concurrent with this finding, histologic examination also showed different characteristic features of the vascular system of the endolymphatic duct-proximal sac areas and of the more distal parts of the endolymphatic sac. These features include the arrangement, quantity, and contents of the periaqueductal bony channels, as well as the organization of the bone containing these periductal bony channels. Findings from this study help the understanding of the anatomy of the human endolymphatic duct. In addition, they support and supplement earlier observations of the structure of the endolymphatic duct. We suggest the possible existence of a periductal vasculature system, similar in pattern to that in the endolymphatic sac, but specialized to work with the duct to aid its function. PMID- 1442012 TI - Ischemia of the endolymphatic sac. AB - A decrease in vascular density in the endolymphatic sac was suspected as a factor in the pathogenesis of endolymphatic hydrops in Meniere's disease. The present study was undertaken to explore this possibility by cutting the posterior meningeal artery and the sigmoid sinus above and below the external aperture of the vestibular aqueduct or by incision of the dura adjacent to the sinus in 18 guinea pigs. The lesions in the sac were greater in the segmental ablation of the artery and sinus and were consistently associated with the development of endolymphatic hydrops. Among the lesions shown in the sac epithelia, the intermediate portion was most often and most severely affected with a decrease in rugose formation and a flattening of the tall epithelial cells or replacement of epithelial cells by squamous type cells. A high correlation between the lesions in the intermediate portion and occurrence of hydrops suggests that the intermediate portion plays a greater role in the pathogenesis of endolymphatic hydrops. The sac luminal precipitates known to be increased in human Meniere's cases were decreased or absent in this study, which suggests that the increased amount is unlikely to be the cause of endolymphatic hydrops. The evidence supports the hypothesis that these substances are secreted by the endolymphatic sac. The limited sensory cell lesions seen in the cochleae and saccules are likely to be due to a temporary vascular ischemia and endolymphatic hydrops. PMID- 1442013 TI - Adenylate cyclase modulation of ion permeability in the guinea pig cochlea: a possible mechanism for the formation of endolymphatic hydrops. AB - The pathophysiological mechanisms leading to endolymphatic hydrops in Meniere's disease are unknown. Changes in ionic permeability of the cellular membranes between the endolymph and the perilymph, which alter the composition and osmolarity of the inner ear fluid, may be a major factor in the etiology of endolymphatic hydrops. To determine the possible involvement of adenylate cyclase in the formation of endolymphatic hydrops, we measured the endolymphatic K+, Na+, Cl- activities (AK, ANa, ACl) and the endocochlear potential (EP) by means of ion selective microelectrodes while inner ear adenylate cyclase was activated by perilymphatic perfusion with forskolin. We observed a large ACl increase accompanied by an EP increase during forskolin (2 x 10(-4) M) perfusion and a delayed AK decrease after perfusion. No measurable ANa change was observed. These results suggest that adenylate cyclase may regulate Cl- permeability of the endolymph-perilymph barrier and that adenylate cyclase plays a critical role in acute endolymphatic hydrops in Meniere's disease by altering the osmolarity of the endolymph. PMID- 1442014 TI - CT-scanning of ancient Greenlandic Inuit temporal bones. AB - Additional morphological evidence of former infectious middle ear disease (IMED) was found by CT-scanning in 5 of 6 Greenlandic Inuit crania strongly suspected for former IMED due to earlier examination revealing either bilateral hypocellularity or asymmetry of the pneumatized area of the temporal bones. The CT-scans showed sclerosing and obliteration of the air cells and even destruction of the cellular septae, and a high degree of irregularity of the cells. Sclerosing of the surrounding bone tissue was also found. The findings in one cranium were dubious and could both be regarded as a congenital malformation or an infection in infanthood. CT-scan confirms and even adds to the results of conventional X-ray of temporal bones making hypotheses of paleopathology more reliable. The findings also support the environmental theory of pneumatization of the air cell system in the temporal bones. PMID- 1442015 TI - Effects of various inflammatory mediators on eustachian tube patency. AB - The effects of several inflammatory mediators on the patency of the Eustachian tube were evaluated in 15 mongrel dogs. Histamine, leukotriene C4(LTC4) and D4(LTD4), and platelet activating factor (PAF) were perfused through the Eustachian tube of anesthetized dogs at concentrations detected in human middle ear effusion of patients with otitis media. The patency of the Eustachian tube was then evaluated by perfusion pressure and opening pressure. Histamine at concentrations of more than 10(-5) M caused increased tubal resistance and opening pressure rapidly. LTC4 and LTD4 caused a rapid increase of tubal resistance and opening pressure at far lower concentrations, i.e. 10(-12) M. Doses of PAF over 10(-9) M may cause an increase in the opening pressure. These results indicate that various inflammatory mediators are capable of affecting the Eustachian tube function. PMID- 1442016 TI - Laser-Doppler flowmetry compared to intravital microscopy for assessment of blood flow in the nasal mucosa of the rabbit. AB - Laser-Doppler flowmeter (LDF) studies of the rabbit nasal mucosal microcirculation were compared with intravital videomicroscopy and with flow measured in single blood vessels in order to evaluate the applicability of the LDF technique. Access to the nasal mucosa for a microscope objective was gained surgically through the maxilla. Transillumination for microscopy was achieved through a prism inserted on the contralateral side of the septal cartilage. Blood flow changes were induced by the inhalation of N2, CO2 and O2 and by topically applying the vasoconstricting alpha-adrenoceptor agonist oxymetazoline. The effects were registered by LDF and direct visual observation. Flow in veins and capillaries was calculated using on-line cross-correlation, and off-line a computerized video-analysis system. LDF did not correlate to flow in single veins or capillaries but agreed well with the visual impression. LDF is considered a valuable method for the assessment of over-all blood flow changes in the nasal mucosa. PMID- 1442017 TI - Newcastle disease viral infection in chicken nasal turbinate and maxillary sinus. AB - Newcastle disease virus (NDV) B strain was inoculated intranasally and intrasinusly into unanesthetized chicken which were maintained on a standard commercial mash chicken diet until the age of 21 days after hatch. The lesions induced by NDV following intranasal inoculation usually produced a selective destruction of significant portions of the inner surface of the turbinate scroll, but sinus lesions, though sometimes present in NDV infection, were not common. The chicken sinus was infected by intrasinus inoculation. These results were supported by the amount of virus and mucociliary transport time in the turbinate and sinus. It is suggested that mucus hypersecretion of ostial gland and/or mucociliary activity in the sinus be one of the most important factors in protecting against chicken sinus infection. PMID- 1442018 TI - Immunohistochemical detection of epidermal growth factor receptor in laryngeal squamous cell carcinomas. AB - Laryngeal squamous cell carcinomas from 15 consecutive preoperatively irradiated patients were investigated for the expression of epidermal growth factor receptor (EGF receptor). The study was performed on frozen sections by means of the 5 layer APAAP technique employing an antibody recognizing the extracellular part of the EGF receptor. In sections from 9 of the patients with laryngeal squamous cell carcinoma, normal differentiated epithelia were included. Sections from 6 of these patients, in addition, contained dysplastic epithelia. Expression of EGF receptor-like material was demonstrated in the basal cell layer of normally differentiated laryngeal epithelial and in dysplastic epithelia. Fourteen of the squamous cell carcinomas proved EGF receptor positive. Nearly all cells in the poorly differentiated carcinomas showed positive staining with the antibodies. In moderately to well differentiated carcinomas a reduction in the extent of staining was seen in certain areas. Especially for the epithelial pearls, the staining reaction was localized to the undifferentiated cells in the periphery. This finding corresponds to the staining pattern observed in the basal cell layers of normal epithelial. The present investigation confirms the expression of EGF receptor-like material in normal laryngeal epithelial, dysplastic epithelial and squamous cell carcinoma. The staining pattern was similar to that observed in oral squamous cell carcinomas, predominantly varying inversely with cellular differentiation. PMID- 1442019 TI - Clinical application of exogenous surfactant and high frequency oscillation in Japan. PMID- 1442020 TI - Relationship between PaO2 and lung volume during high frequency oscillatory ventilation. AB - The relationship between oxygenation and lung volume during high frequency oscillatory ventilation (HFOV) was studied. We ventilated anesthetized, tracheostomized adult rabbits that were rendered surfactant-deficient by lung lavage. Lung volume was measured by the 'disconnection technique'. In the first experiment, HFOV was commenced after conventional mechanical ventilation (CMV) for 1 hr. In the absence of sustained inflation (SI), oxygenation improved with time during HFOV. In the second experiment, HFOV was instituted after CMV for 4 hr. In the absence of SI, all animals expired during the experimental period. In the third experiment we ventilated rabbits for 4 hr and then switched to HFOV. We applied SI first and increased mean airway pressure (MAP) by increments of 2 cmH2O every 15 min. However, there was little improvement in PaO2 despite the use of repeated SI and the increase in MAP. We conclude that oxygenation has a linear relationship to lung volume during HFOV, and that secondary lung injury due to long-term CMV impairs the response to HFOV. Therefore, it is important to minimize the risk of such secondary injuries before instituting HFOV. PMID- 1442021 TI - Skin tests of pollen grains of taxodiaceae and cupressaceae in children with bronchial asthma. AB - Atmospheric cedar pollen in the southern region of Okayama Prefecture (situated in south-western Japan) has been counted since 1988. Pollen of different species of the Taxodiaceae family (Cryptomeria japonica, Sequoia sempervirens and Metasequoia glyptostroboides) and Japanese juniper (Juniperus rigida) in the Cupressaceae family, which are propagated mainly in the southern region of Okayama Prefecture, were found among the atmospheric pollen. Scratch tests using the pollen extract from Taxodiaceae and Cupressaceae were performed on children with bronchial asthma. Forty (25%) and 30 (18.8%) of the 160 patients reacted positively to an allergen extract from the pollen grains of Japanese cedar (Cryptomeria japonica) and Japanese juniper, respectively. PMID- 1442022 TI - The effects of rice bran broth bathing in patients with atopic dermatitis. AB - We determined the effects of rice bran broth bathing therapy in 17 outpatients with atopic dermatitis. The rice bran broth used in this study was made in our hospital and distributed to the patients who dissolved it in the bathtub as a medicinal bath. In the case of one patient, redness and itching of the skin increased just after bathing. The patient subsequently discontinued therapy. We followed the other 16 patients who performed rice bran broth bathing for 2-5 months and examined their skin symptoms once a month. The efficacy of this therapy in alleviating skin symptoms was excellent in four of the 16 evaluated patients, good in seven, slightly effective in four, and ineffective in one. None of the 16 patients experienced negative effects of treatment. Recurrence of initial symptoms was not detected in any patient during rice bran broth bathing. Rice bran broth bathing therapy appears to be safe and clinically useful. PMID- 1442023 TI - Possible role of Streptococcus pyogenes in mucocutaneous lymph node syndrome. XV. Potential utility of streptococcal pyrogenic exotoxin toxoid for the prophylaxis and treatment of MCLS. AB - Mice made tolerant to streptococcal pyrogenic exotoxin (SPE) by neonatal inoculation with SPE emulsified in incomplete Freund's adjuvant demonstrated early thrombocytopenia followed by thrombocytosis. This state is the perfect counterpart of patients with mucocutaneous lymph node syndrome (MCLS). We have hypothesized that by inducing tolerance to SPE, the biological activities of the toxin might play leading roles in the pathogenesis of MCLS. In the present investigations, the efficacy of SPE on the prophylaxis and treatment of diseases caused by Streptococcus pyogenes (including MCLS) were monitored using the murine model system accompanied with a platelet-counting technique. The mice, rendered tolerant due to neonatal SPE inoculation and followed by immunization with SPE toxoid about 1 month prior to the provocative injections with SPE, demonstrated an almost complete lack of response to the provocation, keeping platelet counts within the normal range of values (except for a marginally significant thrombocytosis 7 days postprovocation). Moreover, anti-SPE titers of the sera from the mice sacrificed on day 35, at which point the observation was terminated, were proved to be markedly elevated when compared with controls. These findings seem to suggest that immunization with the toxoid could overcome tolerance, resulting in the production of an antitoxin. In a second experiment that examined the effect of administration with rabbit antiserum raised against the toxoid, the antiserum-treated mice demonstrated a transitory thrombocytosis on 7 days postprovocation with SPE, followed by an abrupt decrease in the number of platelets from day 10 onward.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442024 TI - Urinary fibrin and fibrinogen degradation products and the origin of hematuria. AB - We examined urinary fibrin and fibrinogen degradation product (U-FDP) concentrations in pediatric patients with hematuria using the rapid and highly sensitive latex particle agglutination test (LPAT), and assessed the value of this test for the localization of the site of hematuria. Patients with hematuria were divided into two groups: 60 with glomerular hematuria and 46 with non glomerular hematuria. If U-FDP concentrations less than 0.25 microgram/ml are accepted as an indicator of glomerular bleeding, the sensitivity and specificity of localization of glomerular hematuria in the present study were 78% (47/60) and 89% (41/46), respectively. The high U-FDP concentrations observed in patients with non-glomerular hematuria may reflect direct bleeding into the urinary tract. Since all 13 patients with glomerular hematuria and U-FDP concentrations of 0.25 microgram/ml or more had coexistent erythrocyte cylindruria, the U-FDP test seems to be compensated with combined urinalysis for the relatively lower sensitivity. We conclude that a knowledge of U-FDP concentrations by LPAT can be of help in localizing the site of bleeding in hematuria. PMID- 1442025 TI - Nosocomial meningitis due to Campylobacter fetus subspecies fetus in a neonatal intensive care unit. AB - We experienced a nosocomial outbreak of Campylobacter fetus subspecies fetus (C. fetus) meningitis in a neonatal intensive care unit. A cluster of three infants developed meningitis approximately 1-1.5 months after the index patient was admitted. Two asymptomatic intestinal carriers of C. fetus were detected during the outbreak. Our experience indicates that C. fetus can cause nosocomial meningitis in neonates, and asymptomatic carriers may play a role in the transmission of the organism. PMID- 1442026 TI - A mosaic case of isodicentric chromosome 18. AB - A case of mosaicism of isodicentric chromosome 18 is reported. Dicentric chromosome 18 occurs rarely and only five cases of isodicentric chromosome 18 have been documented. A high resolution banding method revealed that the karyotype of the patient was mos 46,XX/46,XX idic(18)(pter-->q21.3::q21.3- >pter), and the ratio of normal and abnormal clones was 1:1. The clinical manifestations, resembling those of trisomy 18 syndrome, were affected by both partial trisomy 18pter-->q21.3 and partial monosomy 18q21.3-->qter. PMID- 1442027 TI - Myelodysplastic syndrome with partial deletion of the long arm of chromosome 5: first report of a case in a child. AB - A childhood case of myelodysplastic syndrome (MDS) with a deletion of the long arm of chromosome 5 (5q-) is reported. The patient was an 8 year old boy who has recurrent angina. Laboratory evaluation revealed the following: hemoglobin 8.1 gm/dl, white blood cell count 4.9 x 10(3)/l with 3% atypical lymphocytes, and platelet count 17.7 x 10(4)/l. A bone marrow aspirate revealed 20% blast cells and dysmyelopoietic changes involving all three marrow cell lines. Karyotype analysis of marrow cells revealed 46,XY,5q- in 100% of the metaphases. These findings led to a diagnosis of MDS with 5q-, which is most commonly found in adult MDS. This case seems to represent an exceedingly rare childhood case of MDS with 5q-. PMID- 1442028 TI - Atelosteogenesis type 3: the first patient in Japan and a survivor for more than 1 year. AB - We report the first patient of atelosteogenesis type 3 (AO3) in Japan. The patient had multiple craniofacial abnormalities at birth, including ocular hypertelorism, a flat nasal bridge, micrognathia and a cleft palate. There was rhizomelic shortness of the limbs and a club-foot. The infant had short broad thumbs in the hands similar to those observed in the feet. There were no chromosomal abnormalities. Radiological examination demonstrated striking hypoplasia of the humerus with proximal rounding and distal tapering giving a 'drumstick' appearance, 'S'-shape configuration of the cervical spine, scoliosis and coronal cleft in the thoracolumbar vertebral bodies. The infant experienced recurrent apnea and persistent severe tracheomalacia, which necessitated tracheostomy at 5 months of age. Despite his multiple skeletal deformities and respiratory problems, this patient survived more than 1 year with motoneuronal developmental delay. PMID- 1442029 TI - Spinal arachnoid cyst in a newborn infant. AB - A male infant was born with asphyxia following a prolonged breech delivery at 39 weeks of gestation. He had a chylohemothorax from birth. Soon after birth he exhibited flaccid paraplegia with an absence of deep tendon reflexes in the lower extremities. At 17 days of age, magnetic resonance imaging (MRI) disclosed a hypodense area in the thoracic cord between C7 and Th4 in T1-weighted images, and spinal sonography revealed an echo-free space compressing the spinal cord in the same region observed with MRI. A spinal cyst was removed surgically at 24 days of age. The cyst was confirmed by pathology to be a true arachnoid cyst between C7 and Th4. The cause of this cyst may have been a spinal cord injury during the perinatal period. PMID- 1442030 TI - Report of a Japanese girl with Marfan syndrome associated with insulin-dependent diabetes mellitus. AB - A 3 year old girl was admitted to hospital in an emaciated condition and with polydipsia in October 1974. Following the diagnosis of diabetes mellitus, she received treatment with insulin. On the first admission, a systolic murmur was noted at the apex of the heart. In 1981, the murmur was found to be continuous with a systolic click, and echocardiography demonstrated a mitral valve prolapse. In 1982, electrocardiography revealed left ventricular hypertrophy, and the patient's X-ray showed vertebral kyphoscoliosis. Ophthalmological examination revealed slightly impaired visual acuity and a mild case of cataracts in 1986. The patient grew to be tall and thin with arachnodactylia of the hands, fingers, feet and toes. These symptoms and findings were compatible with Marfan syndrome, although the ophthalmological findings are not specific for this disease. This patient is the first case in Japan of Marfan syndrome associated with insulin dependent diabetes mellitus, although the relation between Marfan syndrome and IDDM remains unclear. PMID- 1442031 TI - Case report of an insulin-dependent diabetes multiplex family with a pair of identical twins. AB - The following is a case of a family with a pair of identical twins and a family history of insulin-dependent diabetes mellitus (IDDM). A 2 year old identical twin was first admitted to our hospital and diagnosed as IDDM based on diabetic ketoacidosis. His father has been treated with insulin since the diagnosis of IDDM at the age of 17. All family members had the HLA-DR4 and DQA1*0301 alleles, which are strongly associated with IDDM. The DR-DQ haplotypes of the father and both twins were DR4-DQW8 (DQB1*0302), which increases susceptibility to IDDM. Islet cell antibodies were positive only in the index twin at the time of diagnosis. The co-twin was considered to have beta-cell dysfunction based on the result of an intravenous glucose tolerance test. PMID- 1442032 TI - Familial occurrence of growth hormone deficiency and primary hypothyroidism. AB - We examined endocrine function in three male siblings with growth hormone (GH) deficiency and primary hypothyroidism. Low GH responses to various provocative tests were revealed in all three. Exaggerated thyrotropin (TSH) responses to thyrotropin-releasing hormone increased basal TSH levels, and low free thyroxine levels were also found in all three. Additionally, a low testosterone response to human chorionic gonadotropin and low gonadotropin responses to luteinizing hormone-releasing hormone were noted in the youngest sibling. Skull X-ray films, computerized tomography and magnetic resonance imaging revealed no abnormalities of the pituitary gland or sella turcica. The GH gene was intact in all of the children and their parents. We diagnosed all siblings as having GH deficiency and primary hypothyroidism. This is the first report of familial occurrence of GH deficiency and primary hypothyroidism. PMID- 1442033 TI - Intra-operative total enteroscopy for the management of Peutz-Jegher's syndrome. AB - We present a case of Peutz-Jegher's syndrome in an 18 year old female who was followed for gastrointestinal polyps for 13 years from the age of 5 years. The patient was treated four times with surgical or endoscopic polypectomy for gastrointestinal polyps. At the age of 14 years, a combined surgical and endoscopic approach for the management of Peutz-Jegher's syndrome was carried out. A large polyp of the ileum required enterotomy for its removal, and another smaller polyp of the upper jejunum was identified and removed by intra-operative total enteroscopy via the anus. Intra-operative enteroscopy allows one to identify polyps that would previously have been missed. A more complete polypectomy can be performed using this technique, allowing the patient with Peutz-Jegher's syndrome a longer interval between laparotomies and a reduction in symptoms attributed to polyps. PMID- 1442034 TI - The very low birthweight neonate with an interrupted aortic arch and dextrocardia. AB - Type 1A interruption of the aortic arch complex accompanied by mirror-image dextrocardia with situs inversus was diagnosed by counter-current aortography through the radial artery. This technique is useful for aortography of the very low birthweight neonate. PMID- 1442035 TI - [Effects of m-nifedipine on experimental myocardial metabolism and infarct size in rabbits]. AB - The protective effects of m-Nif 15, 30 and 50 micrograms.kg-1 and of Nif 30 micrograms.kg-1 on experimental myocardial infarction and metabolism in rabbits were evaluated. Blood samples were collected simultaneously from the femoral artery and the coronary sinus for examining lactate and potassium balance. In the normal group (n = 8) and the sham ligated group (n = 5), the lactate balance were +17 +/- 1.0 and + 13 +/- 1.1% respectively and the potassium balance were +2.1 +/ 0.08 and +2.4 +/- 0.08%, respectively. After occlusion of the LAD, the lactate and K+ balance reduced to -196 +/- 60.2 and -83.0 +/- 8.2% respectively, and m Nif produced a dose dependent improvement of both balance. After giving m-Nif 15, 30 and 50 micrograms.kg-1 i.v., the lactate balance improved to -60 +/- 9, -48 +/ 6.7 and -24 +/- 1.8% and the K+ balance went up to -32.2 +/- 2.1, -17.6 +/- 0.1, -3.3 +/- 0.06, respectively. In the mean time, Nif 30 micrograms.kg-1 i.v. improved the lactate and K+ balances to -52 +/- 8.6% and -36.4 +/- 3.1%. In another experiment, propranolol 1 mg.kg-1 i.v. improved the lactate balance to 18 +/- 1.2% while the K+ balance increased to +2.0 +/- 0.05%. The area of the myocardial infarct was measured by nitroblue tetrazolium (N-BT) technique 24 h after LAD occlusion.2+ angina pectoris. PMID- 1442036 TI - [Effects of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on tension of rabbit aortic strips]. AB - The purpose of the investigation was to determine the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) on the isolated rabbit aortic strips. The results showed that (1) the rabbit aortic strips with intact endothelium contracted in a dose-dependent manner to exogenous AA between the concentrations of 2.5 x 10(-6) mol/L and 4 x 10(-5) mol/L. EPA did not affect the tension of the relaxing strips, but inhibited the contractile response to AA (2 x 10(-5) mol/L), IC50 = 9.94 x 10(-6) mol/L. DHA showed no significant effect on the contractile response to AA. (2) In the endothelium-damaged rabbit aorta, the contraction of strips to AA was drastically diminished. The inhibitory effect of EPA on the contraction to AA was almost vanished. (3) The contraction of rabbit aortic strips to AA was shown to be abolished by indomethacin (1.5 x 10( 5) mol/L), a cyclooxygenase inhibitor. (4) Radioimmunoassay showed that exogenous AA increased the tissue levels of 6-keto-PGF1 alpha, TXB2 and their ratio. Lower dose of EPA (1.5 x 10(-6) or 1.5 x 10(-5) mol/L) did not affect the tissue levels of 6-keto-PGF1 alpha and TXB2. However, EPA at higher concentrations decreased the metabolites of AA significantly. These findings suggest that exogenous AA induces the contraction of rabbit aortic strips in vitro, which is related to the endothelial cells and mediated by the metabolites(s) of cyclooxygenase, likely endothelium-derived contracting factor (EDCF).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442037 TI - [Effect of cinobufagin on the guinea pig vas deferens and its mechanism of action]. AB - Cinobufagin, one of the active principles extracted from toad venom, was studied on the isolated vas deferens of the guinea pig. The preparation was suspended in a bath containing 10 ml Krebs solution. Isometric tension of vas deferens was recorded on polygraph with a force displacement transducer. Cinobufagin caused a long lasting contraction of the vas deferens of the guinea pig at concentrations of 15-50 mumol/L. The contraction was inhibited following reserpinization and cold storage treatment. The cinobufagin induced contraction was partly blocked by pretreatment with phentolamine and verapamil. These results suggest that the cinobufagin induced contraction of vas deferens might be related to an action which promotes release of NA from the adrenergic nerve terminals. PMID- 1442038 TI - [Synthesis and analgesic action of 6,7-methylenedioxy-1(2H,4H)-acridone derivatives]. AB - Thirteen derivatives of 6,7-methylenedioxy-1 (2H, 4H)-acridone were prepared. The structures of all the compounds synthesized were characterized by elemental analysis, IR and 1H NMR spectra. Compounds IIa, IIb, IId, IIe, IIf increased significantly the pain threshold using the hot-plate method. PMID- 1442039 TI - [Synthesis of molluscacidal synergists]. AB - Chemical molluscicides are useful in schistosomiasis control. A synergist can potentiate the efficacy and reduce the dosage of a molluscicide, thus decreasing the toxicity and environmental pollution. In order to search for potential molluscicidal synergists, 13 compounds of O,O-dialkyl-O-(2-substituted-3 benzofurylacetonitrile-alpha-oxi mino)phosphate or thiophosphate (VI1-13) and 2 compounds of O,O-dialkyl-O-(2-thienylacetonitrile-alpha-oximino)phosphate (X14,15) were prepared. Preliminary test demonstrated that compound X15 had strong synergic effect with sodium pentachlorophenol in combating mollusks. Compounds X14 and VI1,2,3,6,8,10,12,13, also showed some molluscicidal synergistic activity. PMID- 1442040 TI - [Isolation and identification of two new taxane diterpenes from Taxus chinensis (Pilger)Rehd]. AB - Two new taxane diterpenes were isolated from the stem barks of Taxus chinensis grown in Sichuan province of China. Their structures were elucidated by spectral analysis and chemical evidence as 1-hydroxy-7,9-dideacetyl baccatin I(1) and 7,9 dideacetyl baccatin VI(3). PMID- 1442041 TI - [Revision of structure of peimisine]. AB - From the bulbs of Fritillaria siechuanica cultivated in Sichuan province, 5 alkaloids including peimisine (III) were isolated. Structure of peimisine reported in reference (2) was revised as 2 based on 2D-NMR (1H-1H, 1H-13C COSY and NOE), and FR-5 was proved to be peimisine on the basis of their melting point and TLC behavior. It is worthy of noting that 1) configuration of the oxygen at the C-17 in hupehenisine 3 is possibly erroneous; 2) both songbaisine 4 (A or B) and peimisine 2 should be the same compound on the basis of comparison of their 13C NMR data (Table 3) and 1H NMR spectra; 3) configuration of the oxygen atom at C-17 in the jervine-type steroidal alkaloids can not be safely proved by their IR, MS and the chemical shifts of some protons such as the methyls without the X ray diffraction analysis, or the NOE technique and the 13C NMR method. PMID- 1442042 TI - [Studies on naphthoic acid esters from the roots of Rubia cordifolia L]. AB - Four naphthoic acid esters including a new compound were isolated from the roots of Rubia cordifolia L. The new one was named as rubilactone and its structure was elucidated as 3'-carbomethoxy-4'-hydroxy-naphtho[1',2'-2,3] pyran-6-one (I) based on the physicochemical properties and spectrometric analyses (UV, IR, MS, 1HNMR and 13CNMR). The other three were 3'-carbomethoxy-4'-hydroxy-naphtho [1',2'-2,3] furan (II), dihydromollugin (III) and 3-carbomethoxy-2-(3'-hydroxy)isopentyl-1,4 naphthohydroquinone-1-O -beta-D-glucoside (IV). PMID- 1442043 TI - [Anodic stripping voltammetry of promethazine hydrochloride with Nafion coated glassy carbon electrode]. AB - This paper reports the determination of promethazine hydrochloride with Nafion coated glassy carbon electrode by anodic stripping voltammetry. There is a linear relationship between the concentration and peak height in the range of 4 x 10(-8) 5 x 10(-5) mol/L and 8 x 10(-5)-1 x 10(-3) mol/L for promethazine hydrochloride. The raw material and tablets of promethazine hydrochloride have been analysed and good results were obtained. PMID- 1442044 TI - [Comparison of chemical constituents of essential oils from Elsholtzia splendens and cultivated Mosla chinensis by GC-MS analysis]. AB - Xiangru (Labiatae) is a well-known drug used in Chinese traditional medicine. Chemical constituents of essential oils from Elsholtzia splendens and cultivated Mosla chinensis were compared by GC-MS/DS combination on SE-54 capillary column (30 m x 0.32 mm). Forty-three components were identified in Elsholtzia splendens Nakai ex F.Maekawa. The total content of the components in the essential oil was found to be 90.61%. Among them the major constituents are elsholtzia ketone (80.81%). Fifty components were identified in cultivated Mosla chinensis, with a total content of 93.91% in the essential oil. The major constituents are carvacrol (51.11%), thymol (22.00%), and etc. PMID- 1442045 TI - [Construction and application of all-solid-state aconitine electrochemical detector in flow injection analysis]. AB - A new kind of all-solid-state electrochemical detector for very toxic alkaloids such as aconitine, mesaconitine and hypaconitine has been studied. It exhibits Nernstian response for these alkaloids with a slope of 56 mV/decade over the concentration range of 3 x 10(-5)-1 x 10(-2) mol/L at pH 2-7 under the flow condition. Direct potentiometry for the determination of aconitine in Aconitum kusnezoffii Reichb., Aconitum carmichaeli Debx. and Xiaohuoluo Wan showed average recoveries of 98.5, 98.3 and 96.8% and relative standard deviations of 1.8, 2.4 and 3.5%, respectively. It can be used for the determination of very toxic alkaloids in the above mentioned samples by flow injection analysis. It also can be used for the study of the hydrolytic kinetics of aconitine. PMID- 1442046 TI - [Bioavailability of a controlled-release suspension of phenylpropanolamine in healthy volunteers]. AB - A high-performance liquid chromatographic analysis of phenylpropanolamine (PPA) in human plasma is presented. Using direct UV detection the method is sufficiently sensitive to 25 ng/ml for PPA. Single-dose pharmacokinetics of PPA in 10 healthy volunteers taking controlled release suspension (C) or tablet (T), each containing 150 mg PPA was compared. The study described here has shown that the (C) AUC(0-infinity)/(T) AUC(0-infinity) = 1.02 (P greater than 0.4). The controlled-release product of PPA is equivalent to PPA tablet. PMID- 1442047 TI - [Dissolution rate and bioavailability of famotidine tablets]. AB - An automated dissolution test system was used for the determination of the dissolution rate of famotidine tablets, and a mean cumulative dissolution rate of 97.40 +/- 0.31% in 15 min was obtained. To each of six healthy volunteers, 40 mg of famotidine tablets were administered orally, then an automated HPLC with switching column system was used to analyze famotidine in plasma. Variation of drug concentration vs time were fitted to curves. By comparison of calculated values with observed ones, the results could be described as one-compartment model in human. According to a statistic moment algorithm, the results of calculation showed that T1/2 = 2.92 h and Frel = 118.8%. PMID- 1442048 TI - [Morphological and histological studies on the Chinese drug shan-dou-gen]. AB - The Chinese drug "Shan-Dou-Gen" has been used for removing toxic heat, promoting the subsidence of swelling and soothing the sore throat since the ancient time. The authors made a survey of the drug "Shan-Dou-Gen" available in drug markets as well as the plant origin from the drug producing districts. The results showed that the drug "Shan-Dou-Gen" used in different regions in China at present are the roots or rhizomes derived from 9 species: Sophora tonkinensis Gagnep. (Leguminosae), Menispermum dauricum DC. (Menispermaceae), Indigofera amblyantha Craib (Leguminosae), I. carlesii Carib, I., fortunei Craib, I. decoa Lindl. var. ichangensis Y. Y. Fang et C. Z. Zheng, I. kirilowii Maxim. et Palibin, I. potaninii Craib, and Beesia calthaefolia (Maxim.) Ulbr. (Ranuculaceae). In this paper, the morphological characters of the crude drugs are described, compared and illustrated with photographs. The histological structures of the used parts are described, compared and illustrated with line drawings. The morphological and histological similarities and differences found among the above 9 species are summarized, and the key for the identification of the crude drugs is provided. As the drug "Shan-Dou-Gen" derived from different species has different actions and dosages, it is necessary to give different names to different species and use them correctly. PMID- 1442049 TI - [Derivatives of arteannuin B with antileukemia activity]. AB - Arteannuin B (I) was converted to hydroxy lactones (VII, VIII) by a mixture of formic acid and sulfuric acid. Compound VI and Compound VII both showed activity against leukemia P 388 cell in vitro. The rate of growth inhibition were 97.5% and 11.8% for (VI) and 80% and 52.6% for (VII) at the concentration of 10 and 1 micrograms/ml respectively. It seems that the antileukemia activity of 6-membered lactone is higher than that of 5-membered and the methylene group is necessary for the antileukemia activity. PMID- 1442050 TI - Purification and partial characterization of anti-inflammatory peptide from pilose antler of Cervus nippon Temminck. AB - An anti-inflammatory compound was purified and isolated from pilose antler of Cervus nippon Temminck by dialysis, gel filtration and ion-exchange chromatography techniques. HPLC and N-terminal amion acid analysis identified the compound as a homogeneous peptide. The peptide is composed of 68 amino acids and its molecular weight as determined by amino analysis, is about 7200. PMID- 1442051 TI - [The antitumor effect of adriamycin conjugated with monoclonal antibody against gastric cancer in vitro and in vivo]. AB - Adriamycin (ADM), an anthracycline cytotoxic agent, was conjugated with monoclonal antibody 3H11 against gastric cancer via the dextran bridge method. The conjugate 3H11-DEX-ADM, with molar ratio of 3H11 to ADM being 1:73, retained antibody activity to 86%. In the cytotoxicity assay, 3H11-DEX-ADM was shown to exhibit increased cytotoxicity against the target cell line BGC 823. Its IC50 was 3.75 fold less than that of free ADM. The antitumor effect of the conjugate was evaluated in tumor-bearing nude mice. The results indicate that the specific antibody conjugate 3H11-DEX-ADM can significantly inhibit the tumor growth. At the dosage level used in the present study (5 micrograms/mouse x 6), 3H11-DEX-ADM showed an inhibition rate of 51.5%, whereas only moderate inhibition rates were observed with free ADM and the control conjugate NIgG-DEX-ADM. In addition, experiment was performed to evaluate the combined cytotoxicity of 3H11-DEX-ADM and the conjugate of mitomycin C (3H11-HSA-MMC) at different ratios. It was shown that the combination has no synergistic effect when their IC50 was compared with that of the two conjugates used alone. The same result was observed on combinations of the two corresponding free drugs. PMID- 1442052 TI - Effect of Ganoderma polysaccharides on T cell subpopulations and production of interleukin 2 in mixed lymphocyte response. AB - Mixed lymphocyte response was used as a main model through all the experiments In a series of concentrations (25, 50, 100, and 200 micrograms/ml), Ganoderma polysaccharides (GL-B) promoted the production of interleukin 2 (IL-2) in a concentration-dependent manner after initiation of culture for 12 h and increased the total cell recovery as well as that of Lyt 2+ and L3T4+ cells after 4 days of culture. The data also show that the polysaccharides markedly enhanced the cytotoxicity of cytotoxic T lymphocytes, which was increased by 100% at the concentration of 200 micrograms/ml. PMID- 1442053 TI - [Synthesis of oxazolidines from ephedrines as potential prodrugs]. AB - Twenty three (-)- or (+)-2-(substituted phenyl)-3,4-dimethyl-5-phenyl- oxazolidines and five Schiff base derivatives of ephedrine were synthesized by cyclization or condensation with aromatic aldehydes, according to the structure activity relationships and the pro-drug principle. Stereochemical structures were studied for these compounds by spectroanalysis method, and the kinetics of hydrolysis of the oxazolidines were also studied by UV spectra and HPLC methods. The oxazolidines were found to undergo a facile and complete hydrolysis at pH 7.40 and 37 degrees C and the half-lives of hydrolysis were determined. The relationship between structure and stability of the oxazolidine derivatives were discussed. The oxazolidine derivatives are more lipophilic and less basic than the parent ephedrines and their chemical and physical characters are more stable than those of the parent aromatic aldehydes. The stability of the oxazolidine derivatives is affected by the configurations of ephedrines and the positions or Hammett constants of the substituents in the aromatic aldehydes. These results indicate that oxazolidines can be considered as potential prodrugs for ephedrines. PMID- 1442054 TI - [Synthesis and antitumor activities of 4-acylthiol-4-deoxy-4' demethylepipodophyllotoxin analogues]. AB - This paper describes the synthesis and antitumor activity of 4-acylthiol-4-deoxy 4'-demethylepipodophyllotoxin analogues. 4-Mercapto-4-deoxy-4' demethylepipodophyllotoxin prepared from 4'-demethylepipodophyllo-toxin with H2S in the presence of BF3.Et2O, was acylated with different acids using diethyl cyanophosphonate and thus, corresponding 4-acylthiol-4-deoxy-4'-demethyl epipodophyllotoxin analogues were synthesized. These compounds were screened in L1210 leukemia and KB cells, and one compound has activity similar to etoposide, and others were generally weaker than etoposide and corresponding 4-acylamido-4 deoxy-4'-demethylepipodophyllotoxin analogues. PMID- 1442055 TI - [Total synthesis of securinine]. AB - Securinine, an alkaloid having strychnine-like action was synthesized using 1,4 cyclohexanedione as the starting material through the following sequence of reactions: condensation with piperidine, reduction, cyclization catalyzed by mercuric acetate and intramolecular condensation, totally in eleven steps. The IR, 1HNMR and melting point of the synthetic product is identical with those of natural securinine. PMID- 1442056 TI - [Phenyl glycosides from Curculigo orchioides]. AB - One new phenyl glycoside and two new chlorophenyl glycosides were isolated from rhizomes of Curculigo orchioides (Chinese name: Xian Mao, Hypoxidaceae). Based on HRMS, FABMS, 1H-, 13C-NMR and other spectral data as well as chemical evidence, the structures of curculigoside B, curculigine B and C were elucidated to be 2 beta-D-glucopyranosyloxy-5-hydroxybenzyl-2'-methoxy-6'-hydroxybe nzoate (I),24 dichloro-3-methyl-5-methoxy-phenol-O-beta-D-apiofuranosyl (1-6)-beta-D glucopyanoside (III) and 2,4,6-trichloro-3-methyl-5-methoxyphenol-O-beta-D xylopyranosyl (1-6)-beta-D-glucopyranoside (IV), respectively. PMID- 1442057 TI - [Anthraquinones isolated from Morinda officinalis and Damnacanthus indicus]. AB - From chloroform extract of the root of Morinda officinalis, eight anthraquinones were isolated whose structures were deduced to be rubiadin (I), rubiadin-1-methyl ether (II), 1-hydroxyanthraquinone (III), 1-hydroxy-2-methylanthraquinone (IV), 1,6-dihydroxy-2,4-dimethoxyanthraquinone (V), 1,6-dihydroxy-2 methoxyanthraquinone (VI), 1-hydroxy-2-methoxyanthraquinone (VII) and physcion (VIII). Except for compound I and compound II, the other compounds, 1-hydroxy-2 hydroxymethylanthraquinone (IX), 1,3-dihydroxy-2-methoxy-anthraquinone (X), 1,4 dihydroxy-2-methylanthraquinone (XI), 1-methoxy-2-hydroxyanthraquinone (XII) and 1,4-dimethoxy-2-hydroxyanthraquinone (XIII), were isolated from chloroform extract of root of Damnacanthus indicus. Compound V, VI and XIII are new compounds. PMID- 1442058 TI - [Determination of nifedipine by differential spectrophotometry]. AB - This paper reports a new method for determining nifedipine based on the unstable character of nifedipine to light. The absorbance was measured at 350 nm before and after light irradiation. In this method, the contents of nifedipine in tablets were determined by differential absorbance (delta A) and the assay of nifedipine was not affected by other components. Calibration graph was linear in the range of 10-60 micrograms/ml for delta A. The precision of the method was: 1.3% within-day and 1.9% between-days. The average recovery for nifedipine was 99.69%. The method is not only better in specificity and repeatability but also simple and rapid, it would be a new way of assay for nifedipine. PMID- 1442059 TI - [Studies on the dissolution and bioavailability of trimethoprim-sulfadiazine sulfamethoxazole tablets]. AB - A reverse-phase high performance liquid chromatographic method was established for the simultaneous determination of trimethoprim (TMP), sulfadiazine (SD) and sulfamethoxazole (SMZ) in dissolution media. Meanwhile, another reverse-phase high performance liquid chromatographic method was developed for the simultaneous determination of the three drugs mentioned above and their metabolites, N4-acetyl SD and N4-acetyl-SMZ in serum. The in vitro dissolution and in vivo bioavailability of two commercial trimethoprim-sulfadiazine-sulfamethoxazole tablets (A and B) were studied. Drugs were released far more rapidly from A than from B. Significant difference (P less than 0.001) was observed between the T50 s of the same active principles released from A and B. The in vivo processes of all three active principles in 8 healthy subjects taking two tablets each could be described by one-compartment model with first-order absorption and elimination. Compared with A, the relative bioavailabilities of B were 0.83, 0.73 and 0.78 for TMP, SD and SMZ, respectively. Drugs were absorbed more rapidly from A than from B. PMID- 1442060 TI - [Studies on pharmacokinetics of cisplatin-ethylcellulose microspheres for maxillary arterial embolization in dogs]. AB - This paper reports the preparation and pharmacokinetic studies of DDP-EC-ms. The DDP-EC-ms were infused into the maxillary artery of dogs and DDP were infused into the vein as control. The concentration of DDP in peripheral venous blood and tissue was determined by FAAS. Results showed that the DDP level of DDP-EC-ms in the circulating blood was significantly lower than that in dogs given DDP intravenously. However, a significantly higher DDP concentration in tissues was found in dogs treated with DDP-EC-ms. These facts suggest that maxillary arterial embolization with DDP-EC-ms, which significantly reduced the systematic side effects and increased the level of DDP in the embolized local tissue, could achieve the purpose of targeted cancer therapy. PMID- 1442061 TI - [Effects of anisodamine and atropine on the microvasculature of liver, skeletal muscle and foot-pad skin in anesthetized rats]. AB - Rats were urethanised and kept in a constant temperature chamber. The surface temperature of various organs including the liver and the armpit skeletal muscle were monitored with a special mercury thermometer through a narrow hole on the skin cut with scalpel. The temperature of the foot-pad skin were measured using a thermometer as reported previously. After iv of anisodamine or atropine at doses of 12.5-50 micrograms/kg the temperature of the liver and the armpit skeletal muscle were significantly reduced in a dose-dependent manner but the skin temperature was increased. Temperature changes were observed 5 min after drug administration, reaching peak height at about 15 min and maintained for one hour or so. Isoprenaline, dopamine and aminophylline iv showed only a temperature elevating effect, while serotonin and noradrenaline caused only a temperature decreasing effect in all the three organs mentioned above. Although the functional significance of the opposite effects on the microcirculation of different tissues remain to be defined, the effects of atropine-like drugs must result in a redistribution of circulating blood and may have beneficial effects on the survival of some vital organs such as brain, lungs, kidneys ... especially in shock. PMID- 1442062 TI - [Synthesis and antitumor activity of substituted benzaldehyde/cinnamicaldehyde selenosemicarbazones]. AB - According to drug combination principle 26 substituted benzaldehyde/cinnamicaldehyde semicarbazones were synthesized. Twelve of which were not found in literature. The structures of the title compounds were confirmed by elemental and IR, UV, 1HNMR and MS analyses. Thirteen compounds were screened in vivo against Ehrlich ascites tumor cells. Four compounds (VIIf, VIIg, VIIh, VIIm) showed strong antitumor activity. The percent increase in life span were between 46.1%-91.1%. 3-Methoxy-4-hydroxy and 3-methoxy-4-acetyloxy cinnamicaldehyde selenosemicarbazones showed stronger activity and less toxicity with increase of life span of 76.5% (300 mg/kg) and 91.1% (60 mg/kg), respectively. They were worthy to be studied further. PMID- 1442063 TI - [A new skeleton bisditerpenoid alkaloid from Aconitum pukeense]. AB - A novel bisditerpenoid alkaloid named pukeensine was isolated from Aconitum pukeense W. T. Wang (Ranunculaceae). Its proposed structure was suggested by spectral evidence. This bisditerpenoid alkaloid skeleton has not been found previously. PMID- 1442064 TI - [Acuminatin from the aerial part of Epimedium acuminatum]. AB - A new flavonol glycoside, C27H28O10, mp 151-152 degrees C (MeOH), named acuminatin (I), was isolated from the aerial part of Epimedium acuminatum Franch in addition to four known compounds. By means of UV, FAB-MS, EI-MS, 1HNMR, 13CNMR and chemical evidences, the structure of acuminatin was established as 6", 6" dimethylpyrano (2", 3": 7, 8) 4'-methyl kaempferol-3-O-alpha-L-rhamnopyranoside. The known compounds were identified as kaempferol-3-O-alpha-L-rhamnopyranoside (II), quercitrin (III), hyperin (IV) and daucosterol (V). PMID- 1442065 TI - [Effects of astragalus (ASI, SK) on experimental liver injury]. AB - The saponins (ASI, SK) used in this study was extracted from the root of Astragalus membranaceous Bge and Astragalus sieversianus Pull. ASI and SK were found to protect liver from chemical injury induced by CCl4, D-galactosamine and acetaminophen in mice. The two saponins were shown to impede the elevation of SGPT level, decrease the MDA content and increase the GSH concentration in mouse liver. Obvious improvement of histological changes were also observed. The protective action of ASI and SK against the hepatotoxicity was also shown in experiments using primary cultured rat hepatocytes. The average value of GPT in the medium treated with different concentration of ASI and SK (0.00075-0.18 mmol/L) was lower than that in control. Analyzing through multiple linear correlation, we showed that the lowering of SGPT was negatively related to the increase of GSH, positively related to the decrease of MDA in mice given CCl4 or acetaminophen in combination with ASI or SK. These results indicate that the hepato-protective effects of ASI and SK may be due to their anti-oxidation activities, since the content of liver protein in mice given ASI or SK was more than that in the controls. Moreover, the level of hepatic microsomal cytochrome P 450 in all mice given the two saponins were significantly increased, the liver metabolism and immunoregulating action produced by ASI and SK may be also involved in their hepato-protective effects. PMID- 1442066 TI - [Comparison of antiarrhythmic effects of IHC-72 (an iodonium-72), lidocaine and verapamil]. AB - The antiarrhythmic actions of 3,6-dimethylamino-dibenzopyridonium edetate (IHC 72), lidocaine (Lid) and verapamil (Ver) on several models Were compared at equitoxic doses (equal fraction of LD50). The action of IHC-72 against aconitine induced arrhythmia was similar to that of Lid but stronger than that of Ver in anesthetized rats. The effect of IHC-72 on ouabain induced arrhythmia was also similar to that of Lid, but weaker than that of Ver in anesthetized guinea pigs. The activity of IHC-72 to raise electrical ventricular fibrillation thresholds (VFT) was weaker than that of Lid and Ver. The effects of IHC-72 in decreasing the incidence of ventricular premature beat(VP B), ventricular tachycardia (VT), ventricular fibrillation (VF) and shortening the duration of VT yielded by reperfusion were similar to those of Lid anf Ver in vivo. PMID- 1442067 TI - [Effects erythropoietin on experimental anemia in rats with chronic renal failure]. AB - Erythropoietin (EPO) is a glycoprotein hormone secreted by human kidney cells. Human EPO was induced from human embryo kidney cells, isolated and purified from medium by biochemical method in our laboratory. The hypoproliferative anemia in chronic renal failure (CRF) has been assumed to be the result of decreased EPO production by the damaged kidney and of the shortening of the survival of erythrocytes. In this study, CRF anemia was formed 9 weeks after the removal of five-sixths of the renal mass of rats. These anemic rats were divided into 6 groups: treated with different dosages of EPO or physiological saline. The results indicate that EPO has apparent effects on anemia in rats with CRF. It may stimulate erythropoiesis and improve the anemia state of rats with CRF. Hematological parameters (RBC, Hb, PLT, Ht and Rt) may be reverted to normal levels (P less than 0.001). The level of BUN and Cr were significantly decreased. The optimum dose of EPO was 1000 U/kg. All these results show that injection of EPO has therapeutic effect on anemia in rats with CRF. EPO showed no effect on normal rats. PMID- 1442068 TI - [Studies on the tissue schizonticide of malaria parasite: synthesis of derivatives of 2-substituted phenoxyprimaquine, 4-methylprimaquine and quinoxaline]. AB - 2-Substituted phenoxy-, 4-methyl-6-methoxy-8-aminoquinolines and 7-methoxy-5 aminoquinoxaline were condensed with 1-phthalimido-bromo-alkane to yield 2 substituted phenoxy-, 4-methyl-6-methoxy-8-(1-phthalimidoalkyl)-aminoquinolines (compounds 7-10 and 15-20) and 7-methoxy-5-(1-phthalimidoalkyl)aminoquinoxalines (28-30) which were subsequently reacted with hydrazine hydrate to give 2 substituted phenoxy-, 4-methyl-6-methoxy-8-(1-aminoalkyl)-aminoquinolines (11-14 and 22-27) and 7-methoxy-5-(1-aminoalkyl) aminoquinoxalines (31-33), respectively. The 2-substituted phenoxy-6-methoxy-8-aminoquinolines (4-6) were afforded by reduction of the corresponding 8-nitroquinolines (1-3) which were obtained by condensation of 2-chloro-6-methoxy-8-nitroquinoline and substituted phenols. Among them, compounds 25 and 24 were the most effective when evaluated in Plasmodium yoelii infected mice, no parasitemia was observed after a single oral dose of 10 mg/kg. PMID- 1442069 TI - [Studies on the tissue schizonticide of malaria parasite: synthesis of 5 trieluoroacetyl-primaquine and its derivatives]. AB - Primaquine was acylated with trifluoroacetic anhydride to give 6-methoxy-8-(4 trifluoroacetamido-1-methylbutyl) aminoquinoline (compound 2 in Table) and 5 trifluoro-acetyl-6-methoxy-8-(4-trifluoroacetamido-1-methylbutyl )- aminoquinoline (compound 6), bis (trifluoroacetyl) primaquine, which was subsequently hydrolyzed to yield 5-trifluoroacetyl-6-methoxy-8-(4-amino-1 methylbutyl)-aminoquinoline (compound 11), 5-trifluoroacetyprimaquine or trifluoroacetoprimaquine, coded M8506. Similarly, compounds 1, 3-5 and 7-10 were also prepared. Among them, compound 11 appeared to be the most effective by evaluation in mice infected with sporozoites of Plamodium yoelii. With intragastrical dosage of 0.75 mg/kg/d x 3 d of compound 11 to monkeys infected with sporozoites of P. cynomolgi, the radical cure rate of the compound was 92.3%, while that of primaquine was 55.6%. The acute toxicity of compound 11 was two times a low as that of primaquine in mice. The compound did not appear to have mutagenicity, embryotoxicity and chromosomal aberration. When rats received intragastrical doses of 15, 30 and 60 mg/kg/d of compound 11 for 14 and 28 consecutive days respectively, no change was found in histopathological examination at the two lower doses. However, reversible changes were observed at the highest dose. Compound 11, trifluoroacetoprimaquine, was shown to be a promising tissue schizonticide of malaria parasite. PMID- 1442070 TI - [Study on the mass spectrometry of natural products. XI. The MIKES of fast atom bombardment mass spectra of sodium adduct ions of phenylpropanoid glycosides]. AB - The fast atom bombardment (FAB) mass spectra and mass-selected ion kinetic energy spectra [MIKES] of sodium adduct ions [M + Na]+ of six phenylpropanoid glycosides have been studied. An intense sodium adduct appeared in their FAB mass spectra, which was more abundant than the corresponding protonated molecular ion [M + H]+ and may give more definite information about molecular weight of the sample. The MIKES of these [M + Na]+ ions provided a convenient way for sugar sequence analysis of such glycosides. PMID- 1442071 TI - [Glycosides of phenolic acid and flavonoids from the leaves of Glycyrrhiza uralensis Ficsh]. AB - Seven glycosidic constituents have been isolated from the dried leaves of Glycyrrhiza uralensis Ficsh. (Leguminosae). The Structures of these compounds have been identified as 1-O-protocatechuyl-beta-D-xylose (I), apigenin-6,8-di-C- beta-D-glucopyranoside (vicenin-2, II), isorhamnetin-3-O-rutinoside (narcissin, III) kaempferol-3-O-rutinoside (nicotiflorin, IV), kaempferol-3-O-beta-D- glucopyranoside (astragalin, V), quercetin-3-O-rutinoside (rutin, VI), and quercetin-3-O-beta- D-glucopyranoside (isoquercitrin, VII) by chemical method and spectroscopic analysis. Among these compounds, I is a new compound, named uralenneoside; III was reported for the first time in the genus; III to VII were isolated for the first time from the species. II to VII are known biologically active constituents. PMID- 1442072 TI - [Triterpene constituents from Euphorbia nematocypha Hand-Mazz]. AB - Seven triterpenoids have been isolated from the roots of Euphorbia nematocypha Hand-Mazz. through chromatography on 20% AgNO3-silica gel. One of them was identified as a new compound named nematocyphol on the basis of spectral data (IR, EIMS, 1H-NMR and 13C-NMR). Its structure was deduced as IVa. Other compounds were identified as nepehinol acetate (I), germanicol acetate (II), euphol (III), tanaxastanol (Va), 24-methylenecycloartanol (VIa) and nepehinol (VIIa). These compounds were obtained for the first time from this plant. PMID- 1442073 TI - [Direct injection of plasma to determine gliquidone in plasma using HPLC column switching technique]. AB - An automated clean up and concentration method by column switching is described for the assay of gliquidone, a hypoglycemic agent, in plasma. The system uses Merck Lichroprep RP2 (25-40 microns) as short precolumn packing material for on- line clean up and concentration. A Shimpack CLC--ODS (5 microns) is used as analytical column. Water is used as the pretreatment mobile phase and a mixture of methanol--isopropanol--0.2 mol/L ammonium acetate solution (61:5:34) is used as the analytical mobile phase. The plasma is diluted with a solution of 0.2 mol/L acetic acid and injected directly on the precolumn. The low speed of 0.2 ml/min of pretreatment mobile phase during transfer of plasma sample on the precolumn can get recovery of 80.7%. The detection is at 310 nm and the detection limit is 30 ng/ml plasma. The procedure is simple and automatic. PMID- 1442074 TI - [Quality assessment of the traditional Chinese medicine gentian by chemical pattern recognition]. AB - Methanol extracts of 38 samples of the traditional Chinese medicine gentian of different origin were prepared. Data reflecting their chemical constituents as a whole were obtained by HPLC. The Chinese Pharmacopoeia (1990) specified four species of the getiana as authentic. Some samples from the authentic and non authentic gentian were used as the training set of pattern recognition. Chemical features of the gentian samples were selected from among the matching data of HPLC by the SIMCA program. Finally, the selected chemical features were displayed as stars in a semicircular polar coordinate system, resulting in a constellation graph. Quality assessment of the traditional Chinese medicine gentian was accomplished by recognizing the position and path of the stars in the constellation graph. The clusters of the gentian samples in the constellation graph obtained from the HPLC features were consistent with and complement to their plant taxonomy. The vivid graph demonstrated that pattern recognition via chemical constellation promises well a reliable method for assessing traditional Chinese medicines. PMID- 1442075 TI - [Determination of ofloxacin in human plasma and studies of its pharmacokinetics using HPLC method]. AB - Ofloxacin is a new broad-spectrum oral bactericidal antimicrobial agent. Its primary effect is the inhibition of bacterial DNA gyrase. This paper describes the development of a simple method for its determination using HPLC with UV detection. We used a Waters liquid chromatograph equipped with a Model 490 E multi-wavelength detector, a Model 510 pump and a U6K injector. The separation was performed on a Spherisorb C18 column (200 mm x 4.6 mm ID, 5 microns) with a mobile phase of methanol-0.01 mol/L phosphate buffer-0.5 mol/L tetrabutylammonium bromide (35:65:4, pH 2.50). The flow-rate was 1.0 ml/min and detection was at 294 nm. A specimen (0.2 ml) was spiked with the internal standard (norfloxacin) and deproteinized by adding 1.0 ml methanol. The precipitated mixture was shaken and then centrifuged at 3000 x g for 10 min, the supernatant was evaporated at 75 degrees C under a nitrogen stream. The residue was taken up with 0.4 ml of the mobile phase and 50 microliters aliquots were injected into the system. The minimal detectable concentration in plasma is 20 ng/ml. There is a linear relationship between the peak area ratio over the range of 0.5-4.0 micrograms/ml with r = 0.9999. The method has been applied to assay ofloxacin concentration in human plasma. The pharmacokinetic characteristics were studied. PMID- 1442076 TI - [Transdermal properties of timolol and factors affecting its permeability in vitro]. AB - V-C horizontal diffusion cell has been used to carry out the initial study of timolol across intact and stripped hairless mouse skin and human cadaver skin. Also, we have systematically studied the effect of some factors such as hydration time, medium pH value as well as various transdermal enhancers on the permeability of timolol in vitro. We investigated the determination method of timolol by RP-HPLC using YWG-C18 column with water-acetonitrile-triethylamine (87:13:1) as the mobile phase. The results indicated the feasibility of transdermal absorption of timolol. The permeabilities of timolol raised significantly with properly extending of hydration time, increasing of medium pH and with presence of various kinds of transdermal enhancers. With 10% propylene glycol and 1% azone were used conjunctly, they showed obviously synergistic effects. All these studies contributed theoretically and practically to the further development and utilization of timolol in the form of transdermal patch. PMID- 1442077 TI - [Studies on the chemical constituents of Fritillaria thunbergii Miq. III. Isolation and identification of zhebeinone]. AB - A new C- nor D-homo steroidal alkaloid named zhebeinone was isolated from the bulbs of Fritillaria thunbergii Miq. Its structure was determined by spectral analyses and chemical conversion as 5 alpha, 14 alpha-cevanine-3 beta, 20 beta dihydroxy-6-one or C-27 epimer of peiminine. PMID- 1442078 TI - [Structure of swertiapuniside from Swertia punicea Hemsl]. AB - A new xanthone glycoside, swertiapuniside (V), has been isolated from the whole plant of Swertia punicea Hemsl. The structure was elucidated as 1,5,8-trihydroxy 3-methoxyxanthone-8-O-beta-D-glucopyranosyl (1-6)-O-beta-D-glucopyranoside by means of chemical and spectroscopic data. Four other known xanthones mangiferin (I), bellidifodin (II), 1,3,5,8-tetrahydroxyxanthone (III) and swertinolin (IV) were also identified. PMID- 1442079 TI - [Antitumor activity of new antitumor antibiotic C1027 and its monoclonal antibody assembled conjugate]. AB - C1027, a new macromolecular peptide antitumor antibiotic produced by Streptomyces globisporus C1027, shows extremely potent cytotoxicity to cultured cancer cells. The antibiotic is composed of an apoprotein and a chromophore and the latter serves as the active part of the compound. C1027 was separated into apoprotein and chromophore by methanol extraction and the separated parts can be reconstituted to form the active C1027 molecule in phosphate buffer. For determination of the specificity of C1027 reconstitution, the apoprotein was incubated with epirubicin and the chromophore was incubated with H16, a McAb directed against hepatoma cells. Notably, the reconstitution of C1027 occurred neither between apoprotein and epirubicin nor between chromophore and IgG molecule. In addition, bovine serum albumin showed no competition with C1027 apoprotein in binding to the chromophore. Various methods for linking C1027 to McAb were studied and two kinds of immunoconjugates have been prepared: (1) direct conjugate was made by linking C1027 to McAb, using SPDP as a linker agent, (2) assembled conjugate was made by linking and reconstitution, including 3 steps. Firstly, the chromophore was extracted with methanol and stored at -70 degrees C in drak. Secondly, the apoprotein was conjugated to McAb by SPDP and finally the extracted chromophore was added to the McAb-apoprotein conjugate. Determined by clonogenic assay, the IC50 values for hepatoma cells were 42 pmol/L, and 5.5 pmol/L, respectively, for direct conjugate and assembled conjugate. The IC50 value of M3-C1027 assembled conjugate prepared by linking the irrelevant McAb M3 to C1027 was 1,400 pmol/L.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442080 TI - [Rejection of physico-chemical indices for pathological matrix in a quantitative drug design]. AB - In a quantitative drug design, correlation of coefficient matrix of physico chemical indices Xi is often pathological when these indices are highly correlated. The regression equation of biological activity Y about these indices Xi obtained in this case is not stable. In this paper, a method is given to obtain a stable regression equation: giving a critical valne alpha and finding out the indices among which correlation coefficient is not less than alpha. The following are the rules to reject some of them. If Xi and Xj is highly correlated (magnitude of rij greater than or equal to alpha, rij is the correlation coefficient of Xi and Xj), and magnitude of rin greater than magnitude of rjn (rin and rjn are correlation coefficients of Xi and Xj about Y, respectively), than the index Xj is rejected, otherwise, Xi is rejected. Stable equation can be obtained by stepwise regression with the remaining indices. PMID- 1442081 TI - [Preparation and biological activities of monoclonal antibody-streptonigrin immunoconjugates]. AB - The clinic use of streptonigrin (114B), a highly active antitumor antibiotic, is limited by its detrimental effects on normal tissues. In an attempt to improve its specificity streptonigrin was conjugated to anti-human hepatoma monoclonal antibody 3A5 by four different chemical linkage methods. The first method was via water-soluble carbodiimide (EDCI) to create conjugates (1); in the second, an active ester of streptonigrin was applied as a reactive intermediate (2); and in the other two, spacers were put to use for coupling streptonigrin to McAb 3A5 Dextran T-40 (3) or McAb 3A5-bovin serum albumin (BSA) (4). The conjugates showed biological activities and UV spectral characteristics of streptonigrin and 3A5. As determined by clonogenic assay with human hepatoma BEL-7402 cells for 1 hour exposure, the IC50 for conjugate (2), conjugate (3) and streptonigrin were 0.355 ng/ml, 1.23 ng/ml and 22.4 ng/ml, respectively. The potency of conjugates (2) and (3) were 63-fold and 18-fold stronger than that of free streptonigrin. Clonogenic assay with KB cells which weakly react with 3A5 by Elisa showed that the potency of conjugate (2) and (3) were 11-fold and 13-fold weaker than free streptonigrin, respectively. The results suggest that the conjugates of McAb 3A5 and streptonigrin show specific cytotoxicity to target liver cancer cails. The linkage groups of streptonigrin were also discussed. PMID- 1442082 TI - [Synthesis of O,O'-dialkyl-O''-(5-substituted-3-benzothienglyoxylonitrile oximino) phosphates and thiophosphates]. AB - In order to search for potential molluscicidal synergists, eighteen O,O'-dialkyl O''-(5-substituted-3-benzothienglyoxylonitrile oximino) phosphates and thiophosphates were synthesized. Preliminary biological screening showed that compounds I2,3,7,11,12 combined with sodium pentachlorophenate exhibited significant molluscicidal synergism against snails (Oncomelanis hupensis). PMID- 1442083 TI - [Studies on chemical constituents of the roots of Lantana camara]. AB - Six oligosaccharides (I-VI) and six iridoid glucosides (VII-XII) isolated from the ethanolic extract of Lantana camara roots were identified as stachyose (I), verbascose (II), ajugose (III), verbascotetracose (IV), alpha-D-galac-(1-[-6) alpha-D-galac(-1](3)-6-D-gluc(V ) , alpha-D-galac-(1-6)-alpha-D-galac(-1]-(4)6-D )gluc(VI) , theveside (VII), 8-epiloganin (VIII), shanzhsid methyl ester (IX), theviridoside (X), lamiridoside (XI) and geniposide (XII), on the basis of spectral analysis (1H-NMR, 13C-NMR, FD-MS, GC-MS), physico-chemical constants and preparation of derivatives. V and VI were new compounds named lantanose A and lantanose B, respectively. The others were isolated from this plant for the first time. PMID- 1442084 TI - [System of crystal structure analysis on pc computer--NOMCSDP package]. AB - The package of crystal structure analysis--NOMCSDP (Natural Organic Molecule Crystal Structure Determination Package) Version 1.0 has been developed on the widely used IBM PC computer. It can perform the whole task of X-ray crystal structure analysis, as well as can be used for computing crystal structure on neutron diffraction. NOMCSDP has many advantages--easy operation, less needs for specialized crystallographic knowledge, wide applicability of solving structure, and having all the necessary functions. The inexorable trend of X-ray crystal structure analysis in the course of realizing the wide spread use in determining molecular structure of natural products was discussed and the practical uses of NOMCSDP were illustrated with examples. We hope that this version will play active role in the process of promoting routine use of crystal structure analysis. PMID- 1442085 TI - [Studies on the chemical constituents from Aralia elata]. AB - Eight compounds have been isolated from the root bark of Aralia elata. Their structures have been identified by means of physico-chemical and spectral analysis. They are (6'-O-palmitoyl)-beta-sitosterol-3-O-beta-D-glucoside (A5), silphiosideA (A9), chikusetusaponin Ib (A11), araloside A (A12), araloside C (A15), acanthoside D (B1). Compound A10 is a new natural product, named as araloside A methyl-ester. 3-O-beta-D-glucopyranosyl (1----3)[beta-D-glucopyranosy (1----4)]-beta-D-glucopyranosyl-oleanolic acid-28-O-beta-D-glucopyranoside (A16) is a new compound, named as araloside G. Compounds A5, A9, A10, A11, A16, and B1 were isolated for the first time from the plant. 13C-NMR chemical shifts of compounds A9 and A15 were assigned for the first time. PMID- 1442086 TI - [Studies on the analytical method of a new anti-arrhythmic guan-fu base A in rabbit plasma]. AB - Guan-fu base A, a new antiarrhythmic alkaloid with a structure of C20 diterpenoid, was first isolated from the tuber of Aconitum coreanum (Levl.) Raipaics in China in 1966. An analytical method of GC-ECD has been established in this paper for the determination of its concentration in rabbit plasma in order to study its pharmacokinetics in preclinical pharmacology. Guan-fu base A and the internal standard alprenolol (ALP) was found to react rapidly and quantitatively with trifluoroacetic anhydride (TFAA) to produce derivatives GFA-TFAA and ALP TFAA which were identified by GC-MSD. An optimal GC-ECD system for the separation and determination of the derivatives following the sample preparation was established. There was a wide linear range of the method from 10-2 x 10(4) ng/ml (r = 0.9984). The average recovery of Guan-fu base A from the spiked plasma was 97.52%. The coefficient of variation of between-day and within-day were less than 9% and 7%, respectively. The method was used to determine Guan-fu base A in the plasma of 15 rabbits following intravenous administration of 3 dosages of 0.4, 2 and 10 mg per kg of body weight. PMID- 1442087 TI - [Reversed phase high performance liquid chromatography of tetracyclines]. AB - The present paper describes a quantitative determination method of tetracyclines by reversed phase high performance liquid chromatography. The method used a Waters 10 C18 4.6 nm ID x 250 nm reversed phase column, with a mobile phase composed of 14% acetonitrile-3% dimethylformamide-83% water containing 0.02 mol/L citric acid (pH-2.5), the detector wavelength was set at 350 nm, and the flow rate was maintained at 1.0 ml/min. Demethylchlortetracycline, epi demethylchlortetracycline, demethyltetracycline, epi-demethyltetracycline, tetracycline, epi-tetracycline, chlortetracycline and epi-chlortetracycline can be separated highly efficiently. The tetracyclines and their anhydro- products can be separated on the same column with 15% acetonitrile- 15% dimethylformamide- 70% 0.02 mol/L citric acid as the mobile phase, and detected at UV 270 nm. PMID- 1442088 TI - [Obtaining natural light photostability of drugs from lamp light exposure experiments]. AB - The photostability of vitamin B2, vitamin K3, zinc sulfadiazine and vesnarinone, and the equivalent influences of different light sources on the photostability of the above drugs were studied under natural light and lamp lights. From this study, the photostability of drugs under different light sources can be converted to each other, and the natural light photostability of drugs can be conveniently obtained from lamp light exposure experiments. The relationship between the surface reflectance of the above drugs and the cumulative illumination of different light sources can be formulated as R = A + B(Et) + C/(Et + D) accurately, and the cumulative illumination of different light sources irradiated on the above drugs can be converted to each other equivalently. PMID- 1442089 TI - Determination of arctiin and arctigenin in Fructus Arctii by reverse-phase HPLC. AB - The fruits of Arctium lappa L. is an often-used herbal drug in traditional Chinese medicine for the treatment of common cold caused by wind and heat. This drug contained many constituents, principally arctiin, with arctigenin in smaller amount. In this work, arctiin has been isolated from the fruits of Arctium lappa, and then enzymolyzed into arctigenin. The obtained arctiin and arctigenin were characterized and then used as standards for their determination in the crude drug by HPLC. The method is simple, rapid and accurate. PMID- 1442090 TI - [Simultaneous determination of propafenone and its active metabolite in serum by high performance liquid chromatography]. AB - A rapid, sensitive and simple high performance liquid chromatographic method for the simultaneous determination of propafenone (PPF) and its metabolites (5 hydroxypropafenone, 5-OHP; N-depropylpropafenone, NDP) in serum has been developed. Separation of PPF, 5-OHP and NDP was achieved by reversed phase chromatography using a mobile phase consisting of 57% methanol and 43% 10 mmol/L potassium dibasic phosphate (pH 2.7) at a flow rate of 1.0 ml/min on a 5 microns ODS-C18 column. The eluent was monitored at 254 nm. The method showed a good linearity. The recoveries of PPF, 5-OHP and NDP were found to be 99.54 +/- 2.13%, 100.02 +/- 3.66% and 100.48 +/- 3.10%, respectively. Precision studies for both within day and day-to-day at different concentrations provided RSD values of less than 5%. Some commonly used drugs can be determined in the same procedure without interference except phenytoin. This method is well adapted to the therapeutic monitoring of PPF treated patients, as well as for pharmacokinetic studies. PMID- 1442091 TI - [Pharmacognostical studies on Baibu radix stemonae and allied drugs. IX. Determination and evaluation of total alkaloid content in the roots of Chinese Stemona spp]. AB - An acid-dye colorimetric method was reported for the determination of total alkaloids in 53 samples of Baibu drugs from their growing destricts in 14 provinces and municipalities and its average recovery and its linear range were 96.1% (CV less than 4%) and 20-150 micrograms respectively. The relationship between the total alkaloid content, geographical origins and morphology were discussed. The results showed that: 1. the content of total alkaloids of stemona was 0.26-3.1%; 2. that of Stemona sessilifolia was 0.26-2.17% with the highest content of the sample from Nanyang country in Henan Province; 3. that of S. japonica was 0.83-1.43%; 4. that of S. tuberosa was 0.53-3.1% with the highest content of sample from Hengyang in Hunan Province; 5. that of S. parviflora was 0.22-0.74% with the highest content of sample from Qongzhong in Hainan Province; and 6. that of more yellow, solider and stronger samples was higher than that of any other samples. However, that of all bigger samples in shape was not higher than that of smaller ones. PMID- 1442092 TI - [Surface activity of emulsifiers. Part IV. Determination of the contact angle at the interface of two liquids]. AB - A method has been worked out for the determination of wetting contact angle formed at the interface of oil/water and/or aqueous and oleaginous solutions of surfactants, respectively. Contact angle proved to be an accurate and well reproducible index. The size of contact angle decreased logarithmically along with the concentration of tensids. Several samples of the emulsifier series tested, induced interfacial tension in 1-1.5%, and the wetting contact angle did not decrease further above this concentration. Correlation and a non-linear regression was found between the contact angle and the interfacial tension. PMID- 1442094 TI - Sensitive colorimetric determination of copper (II) ions in some chemicals and multivitamins. AB - A sensitive and selective colorimetric method has been devised for the micro determination of copper (II) ions in pure form, some chemicals and multivitamin preparations. The method depends on the formation of stable blue complexes in ammonia medium peaking at 615 nm between copper (II) ions, oxalyldihydrazide and one of the following aldehydes: 4-nitrobenzaldehyde, 2-nitrocinnamaldehyde and formaldehyde with minimum detection limits 0.1, 0.16 and 1.1 ppm, respectively. Several metal ions do not interfere. The optimum reaction conditions were studied and the results obtained were favorably comparable to the diethyldithiocarbamate method. PMID- 1442093 TI - [Effect of interferon and interferon combined with 3-methylcholanthrene on the mixed function oxidase system in the liver of mice]. AB - The authors have studied the effect of human interferon alpha alone, as well as its effect when co-administered with 3-methylcholanthrene, on the mixed function oxidase system (MFO) of mouse liver. The single interferon alpha treatment did not influence the activities of MFO. However it decreased significantly the enzyme-inducing effect of 3-methylcholanthrene during combined treatment. PMID- 1442095 TI - [Effect of pretreatment with immunomodulating agents on the outcome of lymphocytic choriomeningitis virus infection in athymic (nude) and euthymic mice]. AB - Balb/c (euthymic) and nu/nu (athymic) mice were treated intraperitoneally with TP 4 (a synthetic tetrapeptide, thymopoietin sequence analog, Pharmaceutical Product's Factory Gedeon Richter, Budapest, Hungary) or with Mannozym (0.1% zymosan suspension, Institute for Serobacterological Production and Research, HUMAN, Budapest, Hungary), and were infected intracerebrally with LCM virus. Both of the agents contributed to the development of fatal choriomeningitis, consequently they stimulated the cellular immune response in euthymic mice, but the athymic mice, either treated or not, survived the infection, consequently the agents had no effect on the course of LCM virus infection. The results showed that the cellular immune response stimulating effect by both agents was thymus dependent. Using these agents immunostimulatory effect can be realized only in the presence of the thymus or the T-dependent lymphoid system, respectively. PMID- 1442096 TI - [Analytic and biological standardization of Prunus avium extracts]. AB - Novicardine, the acetonic extract of P. avium peduncle which has advantageous cardiotonic effect, was standardized chemically and biologically. Flavonones, flavones, isoflavones and their glycosides were (methanolbuffer solution eluent, gradient elution) detected by reverse phase HPLC technique. It has been found that substances produced from different varieties of cherry peduncle originated from various lands, have the same components and their ratios are similar, but a contradictory statement could be made in the case of sour cherry. The allowed area ratios belonging to some ingredients were stated with reference to dihydrowogonine-7-O-glucoside. The biological experiments were performed on isolated heart preparations. In the organ bath with Locke's solution content the suspended left atrium and the papillary muscle were driven by rectangular electric impulses of 1 msec duration and of 1.7 Hz frequency, whereas the right atria were beating spontaneously. The result of experiments demonstrated that the standard Novicardine improves the contraction force of heart muscle by some 20 25%, and at the same time doesn't exert influence on the basic electrophysiological parameters and doesn't cause significant changes in heart rate. On the basis of investigation of substances having modified componentratio it was stated that extracts could be isolated which have cardiotonic effect four times stronger than that of Novicardine, on the other hand there were some extracts having negative inotropic effect. These effects were brought into connection with families of compounds (mainly glycosides and aglycones). It seems that the big variety of Novicardine can be assigned to the individual sensitivity of heart preparations, and the ratios of the above mentioned compounds. PMID- 1442097 TI - Increase of blood glucose concentrations in diabetic patients with glucagon eyedrops. AB - Hypoglycemic crisis is a common occurrence in diabetic patients. In order to reverse the hypoglycemia, glucagon eyedrops at concentrations of 2.5%, 5.0%, and 7.5% were instilled to the eyes of diabetic patients who were fasted overnight. The glucagon eyedrops raised the blood glucose efficiently in a dose-dependent manner and peaked at 30 min after drug instillation. At 2.5%, glucagon raised the blood glucose 0.83 mmol.L-1 which exceeded the minimal requirement of 0.56 mmol.L 1 increase in blood glucose level at hypoglycemic crisis. At 5.0% and 7.5%, glucagon eyedrops increased the blood glucose level further to 1.76 and 1.91 mmol.L-1, respectively. These results indicate that glucagon can be delivered effectively through ocular route to raise the systemic blood glucose for the treatment of hypoglycemic crisis. PMID- 1442098 TI - Effects of permeation enhancers BL-9 and Brij-78 on absorption of four peptide eyedrops in rabbits. AB - Systemic absorption of 4 peptide drugs through ocular route was enhanced by permeation enhancers, BL-9 and Brij-78. Gonadorelin (LHRH) was the smallest molecule (M(r) = 1200) and its systemic delivery was most efficiently enhanced by BL-9 (17.0-20.8 times) and Brij-78 (13.9-21.5 times). Although bombesin (M(r) = 1620), atrial natriuretic peptides (ANP) (M(r) = 3240), and adrenocorticotropic hormone (ACTH) (M(r) = 4540) had molecular weight ranged widely, their systemic absorption through ocular route was enhanced by BL-9 (6.1-8.3 times) and Brij-78 (6.5-9.0 times) in about the same degree. BL-9 enhanced systemic absorption of peptide drugs faster and reached peak peptide concentrations in 5-20 min. On the other hand, Brij-78 took 20-60 min to reach to peak concentration of peptide drugs in the blood. These results indicate that systemic delivery of peptide drug through ocular route is a feasible one particularly when the absorption enhancers are used. PMID- 1442099 TI - Effect of dizocilpine maleate on monoamines and their metabolites in rat brain. AB - Systemic (ip) injection of dizocilpine maleate (DM, 0.1 and 0.5 mg.kg-1) increased the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid but did not bring about any noticeable change in the dopamine (DA) level in the striatum and limbic area. DM also increased the levels of norepinephrine in the limbic area and 5-hydroxyindoleacetic acid in the hippocampus. Amphetamine increased DA level and reduced DOPAC level in the striatum and limbic area. The behavioral manifestations revealed that DM predominantly evoked circling behavior and ataxia. The results indicate that the mechanism of the behavioral effect of DM may be different from that of amphetamine. PMID- 1442100 TI - Protective effects of fulvotomentosides on acetaminophen-induced hepatotoxicity. AB - Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effect of Ful on acetaminophen (AA)-induced hepatotoxicity in mice. Ful pretreatment (75-225 mg.kg-1, sc x 3 d) significantly decreased AA (500 mg.kg-1, ip)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Ful pretreatment (225 mg.kg-1, sc x 3 d) decreased hepatic cytochrome P-450, cytochrome b5, and NADPH-cytochrome c reductase by approximately 15-20%. Microsomes from Ful-pretreated mice, incubated in vitro with AA, produced less AA glutathione. A 28% increase in urinary excretion of AA-glucuronide was observed in Ful (150 mg.kg-1, sc x 3 d) pretreated mice. Ful pretreatment had no influence on liver UDP-glucuronic acid concentration, but increased hepatic glucuronyltransferase activity towards AA. In summary, Ful pretreatment protects against AA-induced hepatotoxicity. One of the mechanisms for this protection appears to be the decreased AA toxic activation via P-450, as well as increased detoxication via glucuronidation of AA. PMID- 1442101 TI - Protective effects of fulvotomentosides on cadmium-induced hepatotoxicity. AB - Fulvotomentosides (Ful) is the total saponins of Lonicera fulvotomentosa. In the present study, we examined the effects of Ful on cadmium (CdCl2)-induced acute liver injury in mice. Ful pretreatment (150 mg.kg-1, sc x 3 d) remarkably decreased CdCl2 (3.7 mg Cd.kg-1, iv)-induced liver damage as indicated by serum activities of alanine aminotransferase and sorbitol dehydrogenase. Distribution of Cd to 12 organs and hepatic subcellular fractions was determined 2 h after Cd challenge. Ful pretreatment did not produce a marked shift in the distribution of Cd to various organs, but markedly altered the hepatic subcellular distribution of Cd, with more Cd bound to metallothionein (MT) in the cytosol, less in the nuclear, mitochondrial, and microsomal fractions. Ful pretreatment produced a dose-dependent increase in hepatic MT as determined by the Cd.hemoglobin assay. In conclusion, Ful protected against Cd hepatotoxicity by inducing MT, which binds Cd in the cytosol and lowers the amount of Cd available to other critical organelles and proteins. PMID- 1442102 TI - Neuroprotective effects of phencyclidine on acute cerebral ischemia and reperfusion injury of rabbits. AB - Acute cerebral ischemia and reperfusion injury of rabbits was produced by permanently occluding the vertebral arteries and temporarily clamping the common carotid arteries for 30 min. Phencyclidine [1-(phenylcyclohexyl)piperidine, PCP] 40-80 micrograms.kg-1 icv 30 min before ischemia significantly attenuated the decrease of the total power of electroencephalogram (EEG) within 30 min of ischemia and improved the recovery of brain electric activity following reperfusion. PCP 20-80 micrograms.kg-1 dose-dependently suppressed the creatine kinase (CK) release during cerebral ischemia and reperfusion, and PCP 40-80 micrograms.kg-1 reduced brain ischemic damage. These improvements indicated that PCP has protective effects on acute cerebral ischemia and reperfusion injury. PMID- 1442103 TI - Acetylcholine contents and muscarinic receptor levels in frontal cortex, corpus striatum, and hippocampus of reserpinized rats and mice. AB - The acetylcholine (ACh) levels in rat and mouse frontal cortex increased 155% and 124%, respectively, 24 h after ip reserpine 3 mg.kg-1. Striatal ACh contents, however, were diminished by 47% in rats and 80% in mice. ACh contents elevated 50% and scopolamine (Scop) depleted the ACh by 47% in mouse striatum 12 h following reserpine. Receptor binding assay showed that 24 h after reserpine the Bmax of [3H]quinuclidinyl benzilate ([3H]QNB) binding to muscarinic receptors increased in frontal cortex (by 33% in rats, by 30% in mice) and decreased in striatum (31% in rats, 26% in mice). In mouse hippocampus the ACh contents, Bmax, and affinity of muscarinic receptors lowered 63%, 19%, and 26%, respectively. But these changes were not seen in rat hippocampus. PMID- 1442104 TI - Protective effect of cycloprotobuxine-A against cardiac arrhythmias induced by ouabain. AB - Cycloprotobuxine-A (CPB-A) 1-4 mg.kg-1 iv increased the dose of ouabain required to induce ventricular arrhythmias in guinea pigs. At the equitoxic doses (1/50 LD50), CPB-A was more potent than cyclovirobuxine-D and amiodarone. Pretreatment with reserpine (5 mg.kg-1 ip), vagotomy or pithing spinal cord did not prevent the action of CPB-A, which indicate that the protective effect of CPB-A may be due to its direct action on myocardium without the involvement of nervous system. In isolated guinea pig ventricular muscles, CPB-A 3 mumol.L-1 consistently decreased the amplitude of oscillatory afterpotentials (OAP) and blocked triggered activity elicited by ouabain. At 30 mumol.L-1, CPB-A abolished the appearance of OAP. It seems that one of the mechanisms for the anti-arrhythmic action of CPB-A was a decrease in the amplitude of OAP. PMID- 1442105 TI - Hemodynamic actions of guan-fu base A in anesthetized rats. AB - Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum coreanum in this institute. GFA exhibited anti-arrhythmic effects in various experimental arrhythmia animal models, and bradycardic actions. In this paper, the hemodynamic action of GFA was investigated. GFA 20 mg.kg-1 iv decreased in heart rate from 420 +/- 51 to 305 +/- 60 bpm (P less than 0.05). The changes of SBP, DBP, LVSP, +/- dP/dtmax, and LVEDP were much smaller or insignificant. GFA (1, 3, 10, 30, 60 mg.kg-1 cumulative iv) increased the heart periods (HP) and QT intervals in a dose-dependent manner, accompanied by a small increase in PQ interval, but did not affect QRS complex. The increase in HP from 138 +/- 11 to 321 +/- 48 ms (P less than 0.01) was mainly due to a prolongation of the diastolic period from 22 +/- 12 ms to 156 +/- 46 ms (P less than 0.01). The triple product of HR x LVET x SBP was also decreased with every dose of GFA. This hemodynamic profile suggests that the bradycardic action of GFA can reduce myocardial oxygen consumption and improve myocardial blood supply, which may be of use in certain cardiac patients. PMID- 1442106 TI - Effects of ketanserin on blood pressure variability in conscious spontaneously hypertensive rats. AB - Computerized analysis of blood pressure (BP) was used to study for the effects of ketanserin (Ket) on BP and blood pressure variability (BPV). Rats were instrumented chronically and BP was sampled every 4 ms by a computer from 2:00 to 14:00. Then a single dose of Ket (3 mg.kg-1) was given iv. BP and heart period (HP) were recorded for the next 30 min. The results showed that Ket lowered systolic BP (26.7 kPa to 21.1 kPa), diastolic BP (20.5 kPa to 15.8 kPa), and systolic BPV (1.3 kPa to 0.94 kPa). Otherwise, a positive relationship was found between antihypertensive effects of Ket and BPV. These findings may be of importance in antihypertensive treatment. PMID- 1442107 TI - Effects of microinjection of picrotoxin into posterior hypothalamus on ventricular electric stability. AB - Ventricular fibrillation threshold (VFT), serum potassium, and monophasic action potentials (MAP) have been assessed before and after microinjection of picrotoxin (Pic) into posterior hypothalamus in rabbits. Pic (2 and 3 micrograms) brought about a biphasic effect on VFT, an initial decrease followed by a notable increase. Pretreatment with spinal cord transection almost abolished the descending phase, whereas pretreatment with vagotomy depressed the ascending phase significantly. Following the microinjection of Pic, serum potassium rose up to 5.0 mmol.L-1 at 30 min. The amplitude of MAP (MAPA) and Vmax were lessened in rabbits, while in vagotomized rabbits, the changes of MAP were aggravated, and the duration of MAP was shortened. Phentolamine counteracted the changes of MAP induced by Pic. These results suggested that the initial decrease of VFT caused by Pic derived mainly from the direct action and myocardial ischemia of sympathetic activation, while its subsequent elevation was caused by vagal activation and hyperkalemia. PMID- 1442108 TI - Protective and anti-arrhythmic effects of dauricine and verapamil on acute myocardial infarction in anesthetized dogs. AB - Dauricine (Dau) 5 mg.kg-1 and verapamil (Ver) 0.15 mg.kg-1 iv followed by infusions of 0.1 and 0.01 mg.kg-1.min-1, respectively, for 30 min, depressed the elevated coronary venous blood LDH and CPK after LAD occlusion. Dau produced antagonistic effects on acute myocardial ischemia-induced ventricular ectopic activities (VE) and ventricular tachycardia (VT). The incidences of VE and VT in Ver group and ventricular fibrillation (VF) in both groups tended to descend. The results suggested that Dau and Ver produced marked protective effects on myocardial infarction and antagonized the acute ischemic arrhythmia. PMID- 1442109 TI - Cytotoxic activity of trewiasine in 4 human cancer cell lines and 5 murine tumors. AB - Trewiasine (TWS) is a mytansinoid compound. It possessed a significant cytotoxic activity against various human cancer cell lines in vitro. U937 cells, which were more sensitive to the TWS, required TWS 1 microgram.ml-1 to inhibit cell growth over 90% (P less than 0.01). TWS also showed activities against murine tumors in vivo, such as the ascitic tumors S180, hepatoma, U14, and solid tumor Lewis lung carcinoma. Depression of leukocytes was not seen when mice were given ip TWS 10 or 50 micrograms.kg-1.d-1 x 7 d. TWS 0.1-1 micrograms.ml-1 caused no sister chromatid exchange induction in Chinese hamster cell line V79. PMID- 1442110 TI - Effect of schisandrin B on lipoperoxidative damage to plasma membrane of rat liver in vitro. AB - The effect of schisandrin B (Sin B) on oxygen free radicals--induced lipoperoxidative damage to plasma membrane of rat hepatocytes was investigated. When the plasma membrane of rat hepatocytes was incubated with iron/cysteine or Vit C/NADPH, the production of malondialdehyde (MDA) and consumption of NADPH increased, while the membrane fluidity reduced. Addition of Sin B (3-25 micrograms.ml-1) to the incubation mixture inhibited all these alterations of the plasma membrane induced by iron/cysteine and Vit C/NADPH. The results indicated that Sin B could maintain membrane stability of rat hepatocytes under oxidative stress. PMID- 1442111 TI - Effects of cantharidin on interleukin-2 and interleukin-1 production in mice in vivo. AB - After cantharidin (0.75, 1.5 mg.kg-1) was given ip 3 times every other day in mice, Con A-induced spleen lymphocyte proliferation, as measured by [3H]TdR incorporation assay, was enhanced from 7,978 +/- 1,780 to 36,631 +/- 8,467 and 29,997 +/- 3,788 dpm in both doses. Interleukin-2 and interleukin-1 production were also increased from 11 +/- 4 to 52 +/- 18, 23 +/- 6 U.ml-1 and from 7,628 +/ 1,477 to 14,532 +/- 2,272, 11,515 +/- 2,862 dpm, respectively. These results suggest that cantharidin potentiates immune response through the release of interleukin-2 and interleukin-1. PMID- 1442112 TI - [Effect of habenular nucleus in 5-HT ascending pressor pathways]. AB - The blood pressure was elevated by the electric stimulation of dorsal raphe nucleus in rats. Microinjection of 5-HT (6 micrograms, 3 micrograms) into habenular nucleus induced pressor effect too, but the heart rate was not much changed. Microinjection of procaine hydrochloride (300 micrograms.microliters-1) into both sides of habenular nuclei, the pressor effect induced by stimulation of dorsal raphe nucleus was alleviated obviously (85% blockade). The data suggested that habenular nucleus participates in the pressor effect caused by the excitation of dorsal raphe nucleus, and 5-HT may be one of the neurotransmitters in the action of habenular nucleus participating in cardiovascular regulatory function. PMID- 1442113 TI - [Effects of benzyltetrahydropalmatine on rat portal vein and guinea pig myocardium]. AB - In isolated rat portal vein, benzyltetrahydrophalmatine (BTHP) 0.3-100 mumol.L-1 dose-dependently increased the spontaneous mechanical activity. However, BTHP 300 mumol.L-1 showed an inhibitory effect on the spontaneous contraction. BTHP 200 mumol.L-1 reversed positive staircase phenomenon to negative ones in left atrium of guinea pig and inhibited the amplitude and Vmax and shortened the action potential duration (APD50) of the slow action potentials induced by high K+ (24 mmol.L-1) in guinea pig papillary muscles. BTHP reduced also the contractile force in papillary muscles of guinea pig. These results suggest that BTHP possesses calcium antagonistic effect in high concentration. PMID- 1442114 TI - [Effect of hippocampal injection of oxytocin on shuttle-box avoidance behavior of rats]. AB - Bilateral dorsal hippocampal injection of oxytocin (Oxy, 50 pg, on each side) in rats impaired the acquisition of conditioned avoidance behavior and accelerated the extinction of conditioned avoidance behavior in shuttle-box. The data suggested that the effect of Oxy on shuttle-box conditioned avoidance behavior of rats was at least partly accomplished via the hippocampus; Oxy affected short term memory as well as long-term memory. PMID- 1442115 TI - [Effects of 4-(4"-(2",2",6",6"-tetramethyl-1"-pipe-ridinyloxy) amino)-4' demethylepipodophyllotoxin on nucleic acids, proteins, and DNA strand of L7712 cells in vitro]. AB - The antitumor activity of GP-7, a new spin-labeled epipodophyllotoxin, was studied by liquid scintillation spectrometry. There were many similarities between GP-7 and etoposide. Both GP-7 and etoposide inhibited the incorporation of [3H]TdR, [3H]UR, and [3H]Leu into DNA, RNA, and protein synthesis in leukemia 7712 cells. The inhibition correlated with drug concentration and duration. IC50 of GP-7 and etoposide on DNA synthesis at 24 h were 0.21 and 0.37 micrograms.ml 1, respectively. The inhibition of GP-7 or etoposide on DNA synthesis retained even after the drug were washed out for 3 h. GP-7 and etoposide caused DNA single strand breaks, with a well concentration-response relationship. These data suggest that the inhibition of DNA synthesis by GP-7 or etoposide is likely due to the damage of DNA template and breaking of single-strand DNA. PMID- 1442116 TI - [Effect of artemether against Schistosoma japonicum]. AB - Artemether (beta-methyl ether of artemisinin) first synthesized by Shanghai Institute of Materia Medica, Chinese Academy of Sciences(1), appears in colorless crystal and is more lipid-soluble than artemisinin. When artemether was given ig or im to mice infected with Schistosoma japonicum for 32-35 d at the dosage of 1/10-1/2 LD50. Its effects in the two administration routes were similar. After artemether 200 mg.kg.d-1 ig or 100 mg.kg-1.d-1 im for 1-2 d was given to mice infected with S japonicum cercariae at different intervals, d 7 schistosomules were more susceptible to the drug with worm reduction rates of 73.9-92.0%. The d 35 adult worms also exhibited susceptibility to the drug and the worm reduction rates were 47.0-70.1%, but less susceptibility to the drug in other developmental stages of schistosomes. The major morphological alteration of adult worms induced by artemether was sustained shrinkage accompanied by atrophy and degeneration of the worm's reproductive glands, eg, the testis in males and ovary as well as vitelline gland in females. The in vitro tests indicated that artemether showed apparent effects on different stages of schistosomes only when a higher concentration of 40 micrograms.ml-1 was used. PMID- 1442117 TI - [Pharmacokinetics of puerarin in rats, rabbits, and dogs]. AB - The puerarin was determined by HPLC with fluorescence detection. The plasma concentration-time course of puerarin in rats and dogs after iv was best fitted to a two-compartment open model, while that in rabbits was best fitted to a three compartment open model. Species specificity was found among rats, rabbits, and dogs, calculated with compartment model program. The T1/2 beta after iv puerarin 9 mg.kg-1 in rats, rabbits, and dogs were 11, 21, and 67 min, respectively. There were no significant differences in pharmacokinetic parameters after iv 4.5-30 mg.kg-1 to rabbits and dogs. PMID- 1442118 TI - Effects of graded restriction of perfusion on circulation and metabolism in the working leg; quantification of a human ischaemia-model. AB - An experimental model used with the intention of mimicking the ischaemic condition in patients with arterial obliterative disease was evaluated. The influence of reduced effective perfusion pressure by increased external pressure on leg blood flow and metabolism was determined during exercise in 10 healthy subjects. Catheters were inserted into the right femoral artery and vein and into the left femoral vein. Supine one-legged (n = 5) or two-legged (n = 5) cycle exercise was performed with the subject's legs in a pressure chamber. Zero and three different levels of local supra-atmospheric pressure were applied over the legs: 30, 50 and 60 mmHg. Three submaximal work loads were used: 24, 48 and 72 W/leg. Leg blood flow was measured by the constant-infusion dye-dilution technique. Samples were also drawn from the femoral artery and vein for oxygen saturation and lactate determinations and arterial pressure was recorded. Exercise blood flow decreased progressively with increasing chamber pressure (P less than 0.001). Exposure to 50 mmHg over the working leg led to a mean reduction of blood flow by 16% and venous oxygen saturation by 12 percentage units (P less than 0.05). Lactate release increased with increasing pressure (P less than 0.05). In summary, local application of moderate positive external pressure over the working leg reduces blood flow in a 'dose-dependent' manner, and as a consequence, femoral venous oxygen saturation decreases and lactate release increases. Thus, this method makes it possible to induce graded ischaemia in human skeletal muscle during exercise in a controlled fashion. PMID- 1442119 TI - Bio-energetic changes in human gastrocnemius muscle 1-2 days after strenuous exercise. AB - [31P]magnetic resonance spectroscopy was used to study the metabolic sequelae of intense muscular activity in gastrocnemius of seven subjects 1-2 days after a 67 mile bicycle ride. The muscle was examined at rest, during a test exercise and during recovery from test exercise. Post-ride and pre-ride results were compared. At rest, the ratio of phosphocreatine to ATP (PCr/ATP) was increased post-ride; during test exercise PCr/(PCr+Pi) was lower post-ride; and the recoveries of PCr, Pi and PCr/(PCr+Pi) after test exercise were delayed, with decreased 'overshoot' of PCr/(PCr+Pi) (which is due to recovery of Pi to below its resting value). Mild mitochondrial damage (perhaps due to exposure to high cytosolic [Pi] during the bicycle ride) may explain some of these results. In contrast to reports of largely eccentric exercise there was no increase in resting Pi/ATP. We have thus demonstrated perturbations of muscle bio-energetics 1-2 days after strenuous exercise, in the absence of convincing enzymological evidence of muscle damage. PMID- 1442120 TI - Influence of prostaglandins and a prostaglandin H synthase inhibitor on cervical secretion of the guinea-pig. AB - The modulatory effects of several prostaglandins and a prostaglandin H synthase inhibitor (indomethacin) on basal as well as nerve stimulation induced secretion from the cervical glands of the guinea-pig were studied. Hypogastric nerve stimulation resulted in a secretory response of +113%. Indomethacin dose dependently inhibited this secretory response. Prostaglandins E2, F2 alpha and I2 inhibited and 19-OH prostaglandin E1 reduced nerve stimulation induced secretion. Prostaglandin I2 and 19-OH PGE1 markedly enhanced basal secretion, while indomethacin as well as PGE2 and PGF2 alpha did not induce any secretion of cervical glands. However, PGF2 alpha in combination with the alpha-adrenergic blocker phentolamine resulted in an increase in secretion. The inhibitory effect of prostaglandins on cholinergic secretory innervation might be due to stimulation of adrenergic nerves exerting an inhibitory influence on cholinergic secretomotor innervation. It is suggested that PGI2 and 19-OH PGE1 exert postjunctional stimulatory effects on the secretory lining and that a lack of secretory effect of PGF2 alpha at least in part may be due to stimulatory effects on adrenergic neurons, inhibiting cholinergic secretomotor transmission. Thus, in this in vitro study it is shown that metabolites of the arachidonic acid cascade and a prostaglandin H synthase inhibitor can modulate cervical secretion and thus maybe influence fertilization. PMID- 1442121 TI - Protein kinase C activity in rat renal proximal tubule cells. AB - The presence of protein kinase C (PKC) in proximal tubule cells of the rat kidney is established by means of immunodetection and by the demonstration of calcium- and phospholipid-dependent, staurosporine-inhibitable histone phosphorylation. The calcium-dependence of renal PKC is described. Maximal activation of the enzyme (178.2 and 258.8 pmol P1 mg-1 min-1 for cytosol and membrane respectively) was achieved with 5 microM of Ca2+. Phorbol 12, 13 dibutyrate (PDBu) translocated PKC from cytosol to membrane in a dose- and time-dependent fashion, while 4 alpha phorbol 12,13-didecanoate produced no significant effect on translocation. Cytosolic PKC activity was compared in immature and mature tissues (10- and 40 day-old kidneys). Basal activity was found to be significantly higher (P less than 0.05) in immature cells (272.8 vs. 157.5 pmol Pi mg-1 min-1). PDBu at 10(-6) M for 15 min reduced immunoreactivity in the soluble fraction of both groups, which was accompanied by a significant decrease in kinase activity. We speculate that the high PKC activity in the infant kidney plays a role in cell growth. PMID- 1442122 TI - Metabolic rates of minke whales (Balaenoptera acutorostrata) in cold water. AB - Body temperature, blubber thickness and lung capacity (Vc) were recorded in newly killed minke whales, while respiratory frequency (f) was determined in free swimming animals. Mean deep (thoracic) body temperature was 34.7 +/- 0.8 (SD) degrees C (n = 14). Weighted mean core/blubber interface temperature in animals caught in 2.5-5.5 degrees C water was 28.8 +/- 1.7 degrees C (n = 8). The minimum average rate of sensible heat loss (HLs) was 3.81 +/- 0.53 (SD) W kgw-0.75 (n = 8) in animals with body masses (w) in the range of 1840 to 5740 kg, HLs being inversely proportional to w (HLs = -2.98 10(-4) w +4.89 W kgw-0.75 (n = 8, r2 = 0.73, P less than 0.01)). The average rate of respiratory heat loss (HLr) was 0.26 +/- 0.04 (SD) W kgw-0.75, regardless of w, in the same 8 animals. Total rates of heat loss (HL = HLr+HLs) in 2.5-5.5 degrees C water ranged between 3.40 and 4.87 W kgw-0.75, with an average of 4.06 +/- 0.52 (SD) W kgw-0.75 (n = 8). Estimates of oxygen consumption based on records of f and Ve, and data on oxygen extraction from other cetaceans, yielded a range of metabolic rates which compared nicely with the calculated HL values. PMID- 1442123 TI - Changes in high-energy phosphates in rat skeletal muscle during acute respiratory acidosis. AB - We used 31P magnetic resonance spectroscopy to study changes in phosphorus metabolite concentrations in rat skeletal muscle during respiratory acidosis (14 and 20% inspired CO2) and recovery. As intracellular pH fell (from 7.05 to 6.75 after 20 min of 20% CO2), intracellular [P(i)] increased by up to 50% while phosphocreatine concentration decreased by up to 8%. The sum of all intracellular phosphates remained constant. [ADP] decreased by up to 40% in accordance with the creatine kinase equilibrium but the phosphorylation potential [ATP]/([ADP][P(i)]) was preserved as a result of increased [P(i)]. This adjustment may be a mechanism for maintaining mitochondrial ATP synthesis despite low pH. Eventually this increase in cellular [P(i)] could lead to slow efflux of P(i) from the skeletal muscle cell contributing to the hyperphosphataemia of acute respiratory acidosis. PMID- 1442124 TI - Effects of Amrinone on shortening velocity, force development and ATPase activity of demembranated preparations of rat ventricular myocardium. AB - This study analyses the effects of Amrinone (bipyridine derivative with phosphodiesterase inhibitor properties) on the myofibrillar apparatus of rat myocardium. Thin trabeculae were isolated from the right ventricle and chemically demembranated. Force development and shortening velocity were measured during maximal calcium activations (pCa = 4.45) in control conditions and in the presence of 1-3 mM Amrinone. Maximum shortening velocity was obtained both from extrapolation of the force-velocity curve and with the slack test method. Amrinone was found to significantly reduce maximum shortening velocity and force development. Myofibrils and myosin were prepared from rat ventricular myocardium and their ATPase activity was assessed in control conditions and in the presence of Amrinone (0.3-6 mM). Ca-Mg dependent myofibrillar ATPase activity which was determined at low ionic strength was depressed by Amrinone in a dose-dependent way. Ca-stimulated ATPase activity determined at high ionic strength in myofibril or myosin preparations was not affected. Furthermore, Amrinone did not influence the pCa-ATPase activity curve of the myofibrillar preparations. A comparison between the inhibitory effects of Amrinone on myofibrils prepared from euthyroid rats and myofibrils prepared from hypothyroid rats was carried out. The ATPase activity was significantly less depressed in myofibrils prepared from hypothyroid rats than in those prepared from euthyroid rats. These results provide the first evidence of an effect of Amrinone on ATP splitting and force generation in the myofilament system of cardiac muscle. PMID- 1442125 TI - Force production in voltage-clamped human atrial muscle. AB - Human atrial muscle preparations obtained during open heart surgery were mounted in a sucrose gap. Force and membrane currents were recorded during voltage clamp. After a 20-s rest, 10 clamps from a holding potential of -40 to 0 mV at 1.0 Hz were given. This was followed by a test clamp (called 1) of a varied duration and amplitude and two more test clamps (called 2 and 3) as during the priming period. Peak force of contraction 1 (F1) was independent of clamp duration from 2s to about 100 ms but declined at shorter durations. Peak force of contraction 2 (F2) and 3 (F3) increased with the duration and became potentiated. Increasing the clamp amplitude raised F1 to an optimum value at about +10 mV and there was a decline at higher voltages. Both F2 and F3 increased at higher amplitudes. A conventional bell-shaped current-voltage relation for the second inward current was obtained during clamp 1 with maximum inward current around -10 mV. In control experiments on isolated human myocytes peak current was recorded at somewhat more positive potentials. The relation between F3 and F2 was linear both when duration and amplitude of clamp 1 was varied. The slope of the line, interpreted as a measure of recirculation of activator calcium, was 0.4. It is concluded that force during voltage clamp in human atrial muscle is similarly related to membrane voltage as previously reported for guinea pig and ferret preparations. PMID- 1442126 TI - Intra-neural electrical stimulation of cutaneous nociceptive fibres in humans: effects of different pulse patterns on magnitude of pain. AB - A study was performed to elucidate how different impulse frequencies and impulse patterns in cutaneous nociceptive fibres influence the subjective magnitude of pain. Groups of nociceptive A delta and C fibres were co-activated by electrical intraneural stimulation at constant intensity in cutaneous fascicles of the peroneal nerve in healthy human subjects. The resulting pain sensations were rated on a modified visual analogue scale. Five-second trains were administered randomly at irregular intervals of at least 30 s. Five of the stimulus patterns had regular interpulse intervals, corresponding to frequencies of 1, 2, 4, 10 and 15 Hz, and three other patterns were constructed to mimic to some extent the initially phasic and subsequently slowly adapting discharge patterns which may be encountered in recordings from human nociceptors. The results from these experiments using stimulation frequencies within physiological discharge ranges for human nociceptors indicate that the subjective magnitude of pain increases monotonously as a function of stimulus frequency, and that patterns mimicking nociceptor discharges in response to natural stimuli give rise to greater peak magnitudes of pain than artificial regular patterns with a corresponding number of impulses. PMID- 1442127 TI - Thalamic nociceptive mechanisms in cats, influenced by central conditioning stimuli. AB - Field potentials and single cell activity evoked by tooth pulp (TP) stimulation were studied in the ventrobasal (VB) complex of the cat. The experiments were performed using a conditioning-test paradigm. Evoked cell activity or field potentials following TP stimulation was used as a test. Conditioning stimulus was given to different regions of the thalamic central lateral nucleus (CL). Conditioning electrical stimulation in medial (ML 2.8-3.6 mm) parts of CL induced a depression of the TP evoked response in 10 cells. Stimulation sites in lateral CL (ML 3.6-4.2 mm) induced facilitation in eight cells and decreased activity in seven cells. Tooth pulp evoked field potentials in thalamus were facilitated by a preceding stimulation in lateral CL. Cells in the lateral parts of CL are suggested to induce an increased activity in cells in the VB complex which mediate nociceptive information. This effect is suggested to be mediated via a CL induced disinhibition at a reticular thalamic (RE) or at a VB complex level. The medial parts of CL seem to give a traditional feedback inhibition on VB cells. Such an effect is also suggested to be mediated via the RE complex. The importance of these findings are discussed with relation to changes in the thalamus that may occur following long lasting nociceptive stimulation. PMID- 1442128 TI - Inefficiency of bilateral amygdaloid lesions to reduce the transient motor reactions exhibited by swine during exposure to CO2. AB - The aim of the study was to evaluate from the ethical point of view the importance of transient muscular jerks commonly exhibited by swine at an early stage of pre-slaughter CO2-anaesthesia. The influence of 5 min restraint upon plasma concentrations of adrenaline (A) and noradrenaline (NA) was studied in swine (n = 6) before and after bilateral lesioning of the amygdaloid region of the brain, as were the motor reactions of the same and three other animals during 1 min exposure to 80% CO2. The A and NA responses to the restraint became almost extinguished after amygdaloid lesioning in three of the animals, were reduced by about 50% in one swine, whereas no reduction was seen in the other two animals investigated. The amygdaloid lesioning did not visibly influence the latency for, and the duration and intensity of the muscular jerks manifested by the swine during the CO2-exposure. The results do not favour the possibility that transient motor reactions exhibited by swine during pre-slaughter CO2-exposure are manifestations of emotional stress. Instead, the study indirectly supports the idea that the cause of the muscular jerks may be disinhibition of subcortical motor centres being inactivated by the CO2-anaesthesia somewhat later than neocortical cells normally exerting the inhibition. PMID- 1442129 TI - IGF-I binding and IGF-I expression in regenerating muscle of normal and hypophysectomized rats. AB - Binding of iodinated IGF-I to tissue sections from regenerating muscle was studied by autoradiography in normal and in hypophysectomized rats. Binding of IGF-I was low in control muscle in both groups of animals, but increased transiently about 10-fold during regeneration after injury. Maximal binding occurred later in hypophysectomized rats than in control rats, and there was also a slower regeneration process in these animals. IGF-I, as demonstrated by immunohistochemistry, and IGF-I mRNA, as demonstrated by in situ hybridization, were expressed by the regenerating muscle cells in both groups of animals. It is concluded that locally produced IGF-I is the most likely ligand for IGF-I receptors during muscle regeneration. PMID- 1442130 TI - The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis. AB - We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2 chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments. PMID- 1442131 TI - Power spectral analysis of heart rate and blood pressure variability in anaesthetized dogs. AB - Short-term oscillation of heart rate and blood pressure are mainly regulated by the automatic nervous system. It has been proposed that non-neural factors, such as changes in intrathoracic pressure, can strongly modulate this rhythmicity. Our aim was to evaluate the effect of changing intrathoracic pressure and central autonomic nervous activity on heart rate and blood pressure variability. Evaluation was performed by using spectral analysis techniques with autoregressive modelling. The variability in heart rate and blood pressure remained in animals with open chest or paralysed respiratory muscles. After vagotomy, the variability in heart rate decreased, but not that of blood pressure. Total spinal anaesthesia elicited a decrease in the variability in blood pressure. The pharmacological blockade of alpha- and beta-receptors further decreased both variabilities. It was concluded that in anaesthetized dogs heart rate and blood pressure variability are mainly of central origin and non-neural factors have only minor effect on these central rhythms. High (> 0.15 Hz), medium (0.07-0.15 Hz) and, obviously low (0.00-0.07 Hz) frequency variations in heart rate are mostly mediated vagally. In blood pressure, medium and obviously low frequency variations are modulated by sympathetic nervous system, whereas high frequency variations are secondary to the heart rate variation. PMID- 1442132 TI - Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats. AB - Myocardial capillary exchange capacity was investigated by stereologic and functional techniques in parallel during pressure-overload cardiac hypertrophy and after long-term antihypertensive therapy with the vasodilator felodipine. In 26-week-old female spontaneously hypertensive rats (SHR) blood pressure increased by 25% and left ventricular weight (LVW/BW) increased by 18% compared to Wistar Kyoto rats (WKY). Myocardial capillary surface and volume densities normalized for organ weight were similar in both ventricles for both strains. Moreover, capillary surface density was higher sub-epicardially (EPI) than in the subendocardium (ENDO) in the left ventricle of SHR. Thirteen weeks of felodipine therapy (SHR-Felo) normalized blood pressure without affecting LVW/BW although a transition from concentric to eccentric hypertrophy is known to occur. Myocardial capillary surface and volume densities and the left ventricular ENDO-EPI-gradient in surface density were similar to untreated SHR. However, felodipine-treatment increased right ventricular weight and capillary volume density. Functional capillary exchange was estimated in terms of permeability surface area products (PS) for Cr-EDTA and vitamin B12 and normalized for organ weight. PSCr-EDTA, PSB12 and the ratio PSCr-EDTA/PSB12 (an index of capillary permeability) were similar in SHR and WKY. Furthermore, the relation between functional and stereological indices of exchange capacity was investigated in a multiple linear regression analysis. However, no significant correlation between PS and neither capillary surface nor volume density was found. In conclusion, myocardial capillary exchange capacity was well adapted to the pressure overload cardiac hypertrophy present in female SHR. Despite induction of right ventricular hypertrophy, felodipine-treatment did not affect capillary exchange capacity. Furthermore, when functional and stereologic estimates were performed in parallel, the importance of dynamic factors for myocardial capillary exchange capacity (e.g. heterogeneity) was illustrated. PMID- 1442133 TI - Lipid peroxidation capacities in the myocardium of endurance-trained rats and mice in vitro. AB - The endurance-training programme in Experiment 1 (Exp. 1) consisted of a total swimming time of 149-159 h per male Han Wistar rat and in Experiment 2 (Exp. 2) the male NMRI-mice run on a treadmill at a speed of 25 m min-1 1 h per day, 5 days a week for 3 weeks. One group of the rat hearts was perfused with 0.3 mM cumene hydroperoxide (CumOOH) while the others were fractioned (mitochondria, sarcolemma and sarcoplasmic reticulum) and these cell fractions and homogenates were used to determine the total concentration of peroxidative lipids and the susceptibility to lipid peroxidation. The perfusion with CumOOH caused the release of thiobarbituric acid reactive substances (TBARS) into the perfusate. The release of TBARS from the trained hearts was smaller than that of the control hearts (P < 0.01). The concentration of TBARS was also smaller in the myocardium of the right ventricle of the trained rats (P < 0.01). The concentration of reduced GSH remained at a higher level after the CumOOH perfusion suggesting a better redox state in the hearts of trained animals. The concentration of the lipids susceptible to lipid peroxidation was lower in the homogenates of the trained rat hearts (P < 0.05). However, this decrease could not be explained by any of the tissue fractions used when studied in rat hearts. In Exp. 2 the total concentration of lipids susceptible to peroxidation remained unchanged in the mice hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442134 TI - Vasoconstrictor reactions in spontaneously hypertensive rats versus Wistar Kyoto can be increased or decreased depending on the conditions of perfusion. AB - The reactions of resistance vessels in SHR and WKY hindquarters were compared during saline or blood perfusion. During saline constant-flow perfusion at all initial pressures (80-200 mmHg) sympathetic vasoconstrictor effects were greater in SHR than those in WKY. During perfusion at constant and equal pressure vasoconstrictor responses were greater in SHR vs. WKY only at high pressure--200 mmHg. On the other hand, under constant pressure conditions at lower pressures (80 and 120 mmHg) sympathetic stimulation induced weaker responses in SHR than in WKY, which at, for example, 80 mmHg was the case at every frequency of sympathetic stimulation used (2-20 Hz). Also, the responses to exogenous noradrenaline and vasopressin occurred during perfusion at low (80 mmHg) and for both equal constant-pressure conditions lower in SHR than in WKY. Comparison of sympathetic effects in SHR and WKY during blood hindquarter perfusion revealed similar results. Also, when SHR and WKY responses were compared at their ordinary levels of constant-pressure, sympathetic vasoconstrictor effects in SHR were lower than those in WKY. PMID- 1442135 TI - Effects, release and disposal of endothelin-1 in conscious dogs. AB - Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg-1 min-1) were investigated in conscious dogs. In addition, the disappearance of ET-1 in arterial and central venous plasma after an infusion of 10 ng kg-1 min-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg 1 min-1) and angiotensin II (AII, 2, 5, and 10 ng kg-1 min-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 +/ 0.3 to 243 +/- 23 pg ml-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 +/- 4 to 29 +/- 3 ml min-1 and 87 +/- 16 to 71 +/- 14 mumol min-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t1/2 was 1.1 +/- 0.1 min. Vasopressin increased arterial blood pressure (107 +/- 4 to 136 +/- 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin--in contrast to angiotensin II--is able to increase the plasma concentration of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442136 TI - Polyamines in nerve terminals and secretory granules isolated from neurohypophyses. AB - In isolated nerve terminals from ox neurohypophyses the following concentrations of polyamines [pmol (microgram protein)-1 (mean +/- SEM)] were found: spermine: 2.07 +/- 0.14 (n = 3), spermidine: 0.22 +/- 0.01 (n = 4), putrescine: 0.20 +/- 0.01 (n = 4). In secretory granules isolated from the same tissue, the concentrations were: spermine: 0.57 +/- 0.02 (n = 3), spermidine: 0.07 +/- 0.04 (n = 3), putrescine: 0.13 +/- 0.04 (n = 3). After incubation of isolated nerve terminals with the polyamines, they were taken up as a function of time and concentration, approaching saturation at high concentrations. The kinetic parameters of their synthesizing enzyme, ornithine decarboxylase, in ox neurohypophyseal nerve terminals (apparent Km 0.75 mM and Vmax 22.5 pmol mg protein-1 h-1) were comparable to those previously found in cerebral cortex of rats. When isolated, hemilobes from rat neurohypophyses were incubated in a medium which contained spermidine (5 mM), and were stimulated by 56 mM K+, release of vasopressin was smaller than in control experiments. However, after removal of spermidine and after restimulation, 50 min after initial stimulation, the release was significantly elevated. It is suggested that polyamines may take part in modulation of vasopressin release. PMID- 1442137 TI - Luminal and basolateral uptake and degradation of insulin in the proximal tubules of the dog kidney. AB - In order to determine the major routes of insulin degradation in the body, insulin was labelled with a 'trapped' or 'residualizing' label: [125I]tyramine cellobiose ([125I]TC) and injected intravenously in dogs. In contrast to conventional iodine-labelled insulin (131I-insulin), the [125I]TC-insulin allows measurements of total uptake in specific organs in vivo because the radioactive degradation products do not leave the cells. One h after the injection of trace doses, the amount of radioactivity recovered in the kidney from [125I]TC-insulin was nine times higher than when conventional [131I]insulin was used. In the blood, the amount of acid-precipitable radioactivity was the same for both labelled preparations, indicating similar clearance rates. A comparison of the uptake of insulin in filtering vs. non-filtering (ureter-occluded) kidneys indicated that the uptake of insulin is twice as high through the luminal than through the basolateral cell membrane; after 60 min, 8.9 +/- 0.8% of the injected [125I]TC-insulin dose remained in the filtering kidney and 3.2 +/- 0.2% of the dose was accumulated in the contralateral kidney, with occluded ureter but normal blood perfusion. In both filtering and non-filtering (ureter-occluded) kidneys, the subcellular distributions of [125I]TC-insulin were studied after various times by isopycnic sedimentation in sucrose gradients. No difference between peritubular and tubular uptake was discernible. The intracellular transport was rapid, leading to accumulation of radioactive label in dense lysosomes within 10 min. PMID- 1442138 TI - Changes in muscle fibre type from adolescence to adulthood in women and men. AB - Age-related changes in muscle fibre characteristics have been presented in cross sectional studies previously. The aim of the present study was to investigate longitudinally whether the muscle fibre type composition and muscle fibre area change from adolescence to adulthood. Fifty-five men and 28 women were studied at the age of 16 and again at the age of 27. Biopsies were taken from the vastus lateralis muscle and analysed for fibre types (I, IIA, IIB, IIC) and fibre areas. Different development of fibre type composition with increased age were seen in women and men: the type I percentage tended to increase in the women (51 +/- 9 to 55 +/- 12) and decrease significantly in the men (55 +/- 12 to 48 +/- 13). The fibre areas remained unchanged in both sexes. It is suggested that there is a sex related fibre adaptation to increased age. PMID- 1442139 TI - Neuro-effector characteristics of sweat glands in the human hand activated by irregular stimuli. AB - Intraneural electrical stimulation of cutaneous fascicles in the median nerve was performed in 24 normal subjects and the effects on sweating within the innervation zone were monitored as changes of skin resistance and water vapour partial pressure (wvpp). The aims were: (1) to investigate the response variability between repeated stimulation sequences in the same skin site and between different sites and (2) to compare quantitative effects of regular and irregular stimulation on skin resistance and wvpp. Regional axillary anaesthesia of the brachial plexus eliminated spontaneous and reflex sympathetic activity. With repeated irregular stimulation sequences skin resistance responses from the same skin site varied only slightly between trials. Differences between response curves from two skin sites in the same subject or from different subjects were also small but significantly greater (P < 0.01) than differences between responses to repeated stimulation in the same site. Irregular stimulation with average frequencies of 0.49 Hz and 3.51 Hz gave greater resistance responses than if the same number of stimuli were delivered regularly (P < 0.01). The difference was most pronounced at 0.49 Hz. At an average frequency of 0.49 Hz the stimulation usually evoked no changes of wvpp whereas an average frequency of 3.51 Hz caused an increase of wvpp which was greater with irregular than with regular stimulation in all subjects. We conclude that: (1) sweat responses to sudomotor nerve traffic vary slightly due to local factors in the skin or the terminal nerve endings and (2) irregular sudomotor nerve traffic evokes more sweat than if the same impulses occur regularly. PMID- 1442140 TI - In vivo and in vitro studies on effects of beta-endorphin and naloxone on sex steroids in the water frog, Rana esculenta. AB - The effects of beta-endorphin and its receptor antagonist, naloxone, on progesterone, androgens, and oestradiol-17 beta release in male and female Rana esculenta were studied in vivo and in vitro. In the in vivo experiments the frogs underwent hypophysectomy, gonadectomy or both, or were left intact; the animals were injected with beta-endorphin or naloxone and killed after 15, 30, 90 and 240 min. In the in vitro experiments inter-renal, testis and ovary, all with and without added pituitary, were incubated with beta-endorphin or naloxone for 10, 20, 40 and 80 min. The in vivo and in vitro data from males and females were in agreement. In vivo beta-endorphin increased progesterone in all experimental groups and oestradiol in intact and hypophysectomized frogs, while it decreased androgens in all experimental groups. In vitro beta-endorphin increased progesterone in inter-renal and gonadal tissue, and oestradiol in gonads only, while it decreased androgens in inter-renals and gonads. In vivo and in vitro naloxone induced opposite effects to beta-endorphin. These data suggest that in Rana esculenta, opioids are involved in the modulation of hypothalamo-pituitary inter-renal and gonadal axes. In particular, the data indicate a direct effect of opioids on inter-renal and gonadal sex steroid production. PMID- 1442141 TI - Muscle fibre number following hindlimb immobilization. PMID- 1442142 TI - Glucose in human parotid saliva in response to cold stress. PMID- 1442143 TI - NADPH diaphorase activity and non-adrenergic, non-cholinergic relaxation of the human gastrointestinal tract. PMID- 1442144 TI - Activation of the tubuloglomerular feedback mechanism in an in vitro preparation of the juxtaglomerular apparatus. PMID- 1442145 TI - Training effects on concentrations of immunoreactive superoxide dismutase iso enzymes in human plasma. PMID- 1442146 TI - In vivo and in vitro release of indomethacin from water-soluble and fatty base suppositories. AB - The plasma concentration of indomethacin was measured after the rectal administration of water-soluble and fatty base suppositories in rats. The results were compared with the in vitro indomethacin release from suppositories determined by Paddle method using three different types of membranes: cellulose membrane, artificial sausage membrane and natural sausage membrane. The plasma concentrations of indomethacin during the first 4h after the rectal administration were higher in rats that received water-soluble base suppositories than in those that received fatty base types. When either a cellulose membrane or an artificial sausage membrane of cow protein was used in the Paddle method, the amount of indomethacin released from fatty base suppositories was significantly higher than that from water-soluble base ones. However, the results were reversed when a natural sausage membrane of pig colon was used. The discrepancy in the in vitro experiments using water-soluble base suppositories seemed to be due to the difference of pore size of membrane used. Careful consideration should be given to the membrane used in the Paddle method especially when this method is employed to examine the release of poorly soluble drugs like indomethacin in both water soluble and fatty base suppositories. PMID- 1442147 TI - Histochemical detection of lipid peroxidation in human gastrointestinal, mammary and renal carcinomas. AB - Constitutional lipid peroxidation in randomly selected 32 cases of clinically advanced carcinoma from human gastrointestinal tract (20 cases), breast (8 cases) and kidney (4 cases) was examined histochemically in frozen sections using cold Schiff's reagent. Only two cases of gastrointestinal carcinoma were positive by the reagent. Non-cancerous parenchymal cells were negative. These findings suggest that detectable constitutional lipid peroxidation seldom occurs in either cancerous or normal tissues. The capacity for normal and neoplastic tissues to undergo lipid peroxidation was also studied by incubation with an iron-NADPH pro oxidant system. Normal parenchymal cells showed, to various degrees, a positive reactivity. In gastrointestinal carcinoma, 6 out of 7 cases of well differentiated adenocarcinoma reacted positively, whereas 2 out of 8 cases of moderately to poorly differentiated adenocarcinoma disclosed weakly positive reactions. Mucinous adenocarcinomas (4 cases) were all negative. Signet-ring cell carcinoma (1 case) was positive. One out of 8 cases of breast cancer also showed positive reaction. Four renal cell carcinomas were all negative. Cancer cells have lower capacity to undergo lipid peroxidation than normal cells, when the iron-NADPH pro-oxidant system was employed. In gastrointestinal carcinoma, the ability to undergo lipid peroxidation by the iron-NADPH pro-oxidant seems to be correlated with their histological differentiation. This fact may suggest that differences in lipid composition or the NADPH enzyme system exist between well differentiated and poorly differentiated gastrointestinal malignancies. PMID- 1442148 TI - Effect of taurine concentration on platelet aggregation in gestosis patients with edema, proteinuria and hypertension. AB - To elucidate the relationship between the high concentration of taurine in platelets and platelet aggregation in patients with EPH gestosis (gestosis with edema, proteinuria and hypertension), platelet aggregation and the platelet release response (release of ATP and beta-thromboglobulin) were studied in the washed platelet suspension (PS) obtained from normal pregnant or non-pregnant women and EPH gestosis patients. Platelet aggregation and platelet release response were significantly lower in EPH gestosis patients than in normal pregnant and non-pregnant women. Platelet aggregation, platelet release response induced by ADP and collagen and the aggregation induced by A23187 were inhibited in taurine-loaded PS from non-pregnant women. These results suggest that the decrease of platelet aggregation in EPH gestosis patients was caused by high concentrations of taurine in platelets, which may inhibit the intracellular Ca2+ movement and platelet release response. Therefore, taurine appears to have a protective effect against the hyper-coagulative state in EPH gestosis. PMID- 1442149 TI - Comparison of antitumor activity of new anthracycline analogues, ME2303, KRN8602, and SM5887 using human lung cancer cell lines. AB - In an attempt to predict the clinical activity of newly developed anthracycline analogues, ME2303, KRN8602, and SM5887 in the treatment of lung cancer, we compared antitumor activity of these drugs with that of adriamycin, using six human lung cancer cell lines and two drug-resistant human lung cancer sublines. Taking the pharmacokinetic data into consideration, we evaluated the relative antitumor activity: the ratio of area under the concentration-time curve of each drug to the 50% inhibitory concentration of the drug. Regarding this ratio, ME2303 was more potent than adriamycin, SM5887, and KRN8602. Cross-resistance of the new analogues to adriamycin was investigated using an adriamycin-resistant small cell lung cancer subline, SBC-3/ADM100 and an etoposide-resistant subline, SBC-3/ETP. SBC-3/ADM100 being 106-fold more resistant to adriamycin than the parent SBC-3 showed less resistance to the analogues: 1.80-fold to KRN8602, 3.80 fold to SM5887, and 8.60-fold to ME2303. SBC-3/ETP which was 52.1-fold more resistant to etoposide and 39.5-fold more resistant to adriamycin were also less resistant to the new analogues: 3.27-fold to KRN8602, 9.07-fold to SM5887, and 17.3-fold to ME2303. In conclusion, ME2303 was found to be the most potent agent among drugs tested for the treatment of lung cancer, and KRN8602 can be expected to be beneficial for the treatment of drug-resistant small cell lung cancer. PMID- 1442150 TI - Clinical study of malignant tumors originating in the pelvic region. AB - We evaluated the surgical problems encountered during treatment of 14 patients with malignant tumors originating in the pelvic region at our department. The tumor involved the iliac bone in 6 patients, the ischial bone in 2, the pubic bone in 2, and the gluteal region in 4. Invasion to the sacrum was observed in 7 patients. Twelve patients underwent surgical procedures consisting of intralesional resection in 6, marginal resection in 3, and wide margin resection in 3. Six of the 7 patients with sacral invasion developed local recurrence. Two patients with chondrosarcoma and one with parosteal osteosarcoma survived for 4 or more years, but the mean survival period in those with high grade malignant tumors was 11 months. These findings indicate the difficulties encountered in the treatment of malignant pelvic tumors. PMID- 1442151 TI - Indications and timing of surgery for cholelithiasis associated with valvular heart disease. AB - Twenty patients with cholelithiasis associated with valvular heart disease were studied to assess the need and the optimal time for cholecystectomy. Twelve patients (11 symptomatic and 1 asymptomatic patients) underwent cholecystectomy. The remaining patients were asymptomatic. The levels of the total bilirubin in 9 patients, and of LDH in 15, were higher than normal. In most of the patients, the serum transaminase levels were higher than normal, but in few cases, the levels were higher than 200 IU/l. These abnormal values, however, were not consistently observed in these patients. No clear association between the type and form of valvular heart disease was demonstrated. The type of prostheses used for valve replacement in these patients were ball, tilting disc and leaflet. No significant differences in efficacy were observed among different types of prostheses. The incidence of silent stones is high in patients with valvular heart disease and heart surgery often causes deterioration in patients with cholelithiasis. The recovery of the patients who underwent cholecystectomy before valve replacement were better than those who underwent cholecystectomy after heart surgery. In conclusion, therefore, patients showing any abnormal results in liver function tests should be assessed in detail by abdominal echography and should receive surgical treatment of biliary tract before heart surgery if necessary. PMID- 1442152 TI - Laparoscopic cholecystectomy: report of 42 cases. AB - Our initial experience with laparoscopic cholecystectomy for cholecystitis and cholelithiasis was reviewed in 42 patients and the data were compared with those of 21 patients who underwent conventional open cholecystectomy previously. Only one patient required conversion to an open operation. Three of the 42 patients had minor complications without death in laparoscopic cholecystectomy. The mean time for the laparoscopic cholecystectomy was 100 +/- 40 min, as compared with 79 +/- 21 min for the open cholecystectomy. The average postoperative hospital stay was 11.4 +/- 7.1 days for the laparoscopic procedure and 35.5 +/- 15.4 days for the conventional procedure. The laparoscopic cholecystectomy offers the patients shortened hospitalization and lower complications and can replace the conventional open cholecystectomy in large degree, at least in the uncomplicated cases. PMID- 1442153 TI - Asthma classification by a score calculated from clinical findings and examinations in subjects sensitive to inhalant allergens. AB - Twenty-one patients with atopic asthma were classified into three types according to their symptoms (clinical diagnosis): Ia, simple bronchoconstriction; Ib, bronchoconstriction + hypersecretion; and II, bronchiolar obstruction, and this classification was compared with a classification made according to clinical findings and examinations (score diagnosis). Type Ib asthma was characterized by the increased incidence of eosinophils in bronchoalveolar lavage fluid (BALF), while type II was characterized by ventilatory dysfunction in small airways and the increased incidence of neutrophils in BALF. Four patients, whose expectoration was between 50 and 99ml/day, of the 12 with type Ia assessed by clinical diagnosis were evaluated as type Ib by score diagnosis. One patient with type II by clinical diagnosis was assessed as questionable type II by score diagnosis. In the other 16 patients, the clinical and score diagnoses were the same. PMID- 1442154 TI - Hemodynamic performance of the biventricular bypass system operated in an independent variable rate mode. AB - The present study was undertaken to determine whether a biventricular bypass system operated in an independent variable rate (VR) mode can maintain the entire circulation. Two pusher-plate pumps which incorporated the Hall effect position sensors were used to bypass the right and left ventricles in 10 sheep under fibrillation. The flow distributions of the pump output to the carotid and renal arteries were investigated every 6 h using ultrasonic blood flow meters for 24 h in 5 animals, and the controllability of the VR mode was evaluated in 5 long-term experiments. The carotid artery flow ratio to the pump output decreased significantly from 4.7 +/- 0.8% before the bypass to 2.7 +/- 0.9% after 24 h. However, the renal artery flow ratio did not change throughout the experiments. In the long-term experiments, the animals were kept alive from 3 to 48 days (mean 15.6 days). The mean pump output had been maintained at more than 90 ml/min/kg for the first 7 days. After the surgery, the pump driving conditions were not readjusted in any experiment. The results indicate that the biventricular bypass system operated in the independent VR mode automatically maintains the entire circulation at a satisfactory level. PMID- 1442155 TI - NG-nitro-L-arginine attenuates flow debt repayment in the reactive hyperemic response of the open-chest dog coronary artery: contribution of endothelium derived relaxing factor. AB - To test the hypothesis that the endothelium-derived relaxing factor (EDRF) contributes to coronary vasodilation induced by myocardial ischemia, we examined the effect of NG-nitro-L-arginine (a potent and selective inhibitor of EDRF release) on the coronary reactive hyperemic response in the open-chest dogs. Intracoronary infusion of NG-nitro-L-arginine at a coronary plasma concentration of 5 x 10(-5) M had no effect on hemodynamics and myocardial oxygen metabolism, but attenuated repayment of the flow debt by an average of 20.4% and 20.0% following coronary occlusion for 10 sec and 20 sec, respectively. Concomitant infusion of NG-nitro-L-arginine at the same concentration and 8 phenyltheophylline (a potent adenosine receptor blocker) at a coronary plasma concentration of 10(-5) M further attenuated flow debt repayment following 10 sec and 20 sec of coronary occlusion by 47.7 and 59.4%, respectively. These results indicate that EDRF plays a significant role in the coronary reactive hyperemic response and may cause vasodilation independently of adenosine-mediated vasodilation following coronary occlusion. PMID- 1442156 TI - The role of Kupffer cells in complement activation in D Galactosamine/lipopolysaccharide-induced hepatic injury of rats. AB - To investigate the role of Kupffer cells in complement activation, we used a rat model of acute hepatic injury induced by D-Galactosamine (GalN) and lipopolysaccharide (LPS). In in vivo study, minimal histological changes were observed after i.p. GalN (200 mg/kg) single administration. Complement hemolytic activity (CH 50) decreased to 70% of its initial value 2-3 h after i.p. LPS (1.5 mg/kg) single administration. Massive hepatic necrosis was induced by simultaneous administration of GalN and LPS. After 2-3 h, CH 50 decreased to 70% of its initial value, and deposition of C3 fluorescence (C3) was observed in Kupffer cells. After 4 h, GPT was greatly increased (1286 +/- 240 IU/l), CH 50 was further reduced, and C3 was observed on hepatocyte membranes and in the cytosol. In in vitro study, we used hepatocyte cultures and co-cultures of hepatocytes and Kupffer cells to investigate the participation of GalN, LPS, complement, and Kupffer cells in hepatic cell necrosis. We found no increase of LDH (% leakage) when LPS and complement were added to the medium (22.7 +/- 5.7%). A moderate increase was observed with the addition of GalN (33.2 +/- 2.6%). A remarkable increase was observed only with the addition of GalN, LPS, and complement to the co-culture (50.0 +/- 8.8%). These results suggest that Kupffer cells activated by LPS are very important in promoting acute hepatic injury by complement. PMID- 1442157 TI - Frequency of gamma delta T cells in peripheral blood, synovial fluid, synovial membrane and lungs from patients with rheumatoid arthritis. AB - The percentages and absolute numbers of gamma delta T cells per CD3 positive cells (T cells) in four different compartments, namely peripheral blood, synovial fluid, synovial membrane and lungs from patients with rheumatoid arthritis (RA) and in peripheral blood from healthy controls were studied by two color flow cytometric analysis. The percentages (mean +/- SEM = 6.3 +/- 0.8%, n = 22) and absolute numbers (70 +/- 11/microliters, n = 22) of gamma delta T cells in peripheral blood from RA patients were not different from those of 22 age-matched healthy controls (7.5 +/- 0.9%, 81 +/- 17/microliters, respectively). The gamma delta T cells in peripheral blood from 50 RA patients were, however, significantly decreased in negative correlation with the value of CRP as a marker for inflammation, although they had no correlation with the titer of rheumatoid factor as an autoantibody. The percentages of gamma delta T cells in synovial fluid from 10 patients (3.3 +/- 0.5%, n = 10) or in synovial membrane from 5 patients (4.2 +/- 1.9%, n = 5) and in bronchoalveolar lavage fluid from 6 patients (3.6 +/- 0.8%, n = 6) were not different from those in peripheral blood from the same patients. Thus, gamma delta T cells are not the dominant infiltrating T cell subset in the inflammatory sites of RA patients. PMID- 1442158 TI - Asthma classification by pathophysiology and IgE-mediated allergic reaction: new concepts for classification of asthma. AB - Bronchial asthma was classified by the pathophysiology and by the mechanism of onset of the disease. Forty asthmatics who had serum IgE levels lower than 200 IU/ml were evaluated by two classification methods. 1. In asthma classified by a score based on clinical findings and examinations, the characteristics of the findings and examination results were compared among three asthma types, i.e., Ia. simple broncho-constriction type, Ib. bronchoconstriction+hypersecretion type, and II. bronchiolar obstruction type. Type Ib patients, in addition to manifesting hypersecretion, had a significantly higher proportion of eosinophils in the bronchoalveolar lavage (BAL) fluid compared to other asthma types. Significantly decreased values for ventilatory parameters and an increased proportion of BAL neutrophils were found in type II compared with other asthma types. 2. In a new classification by mechanism of onset, asthma was classified into three types according to the degree of participation of IgE-mediated reactions associated with specific IgE antibodies and serum levels of total IgE: asthma induced by definite IgE-mediated reaction (atopic asthma), possible IgE mediated reactions (asthma), and asthma induced by non-IgE-mediated reaction (asthma syndrome). PMID- 1442159 TI - A case of trans-sternal bilateral thoracotomy for bilateral lung cancer. AB - Trans-sternal bilateral thoracotomy was performed to resect the right upper lobe and the left S1 + 2 + S3, and to complete lymphadenectomy in a 35-year-old female case of lung cancer in whom multiple lesions were suspected. Trans-sternal bilateral thoracotomy was considered to be useful for one-stage surgery in patients in whom bilateral lung cancer is suspected or confirmed, because it provides a sufficient surgical field enabling the resection of lung and lymph nodes. This may be the first case report of trans-sternal bilateral thoracotomy to treat multiple primary lung cancer. PMID- 1442160 TI - Pituitary and ovarian suppression after early follicular and mid-luteal administration of a LHRH agonist in a depot formulation: decapeptyl CR. AB - In order to study its effect on pituitary and ovarian function, a single dose of triptorelin depot (Decapeptyl CR, Ferring) was administered to 12 women in the early follicular (EF,n = 6) or mid-luteal phase (ML,n = 6) of a normal cycle. In all 12 women the initial pituitary and ovarian responses were similar. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) rose to peak values within 48 h, and declined to hypogonadotropic levels within 2 weeks' time. Steroid levels showed a slight to marked rise after injection and fell to hypogonadal values within 1 week. LH suppression was maintained until the 8th week after the injection, while FSH levels rose to normal between the 3rd and 4th week. Estrogen secretion started to be restored in the course of the 7th and 8th week. Menses occurred between the 11th and 13th week after the injection of the drug. This study demonstrates the possibility of rapid induction of a hypogonadotropic and hypogonadal condition in regularly cycling women by administration of a single triptorelin depot. Suppression of pituitary and ovarian function appears to be continued until the 8th week after the injection. PMID- 1442161 TI - The GnRH 10 micrograms test promotes a maximal gonadotropic response in normal women. AB - The authors have compared the results of gonadotropin stimulation with a gonadotropin releasing hormone (GnRH) intravenous bolus of 100 micrograms and of 10 micrograms in a group of eumenorrheic women. They conclude that there are no differences between the responses of the two dosages in normal women. Therefore the authors clarify that the dosage of 10 micrograms of GnRH as a bolus test may be used currently in clinical practice in order to assess gonadotropic function. PMID- 1442162 TI - Auricular acupuncture in the treatment of female infertility. AB - Following a complete gynecologic--endocrinologic workup, 45 infertile women suffering from oligoamenorrhea (n = 27) or luteal insufficiency (n = 18) were treated with auricular acupuncture. Results were compared to those of 45 women who received hormone treatment. Both groups were matched for age, duration of infertility, body mass index, previous pregnancies, menstrual cycle and tubal patency. Women treated with acupuncture had 22 pregnancies, 11 after acupuncture, four spontaneously, and seven after appropriate medication. Women treated with hormones had 20 pregnancies, five spontaneously, and 15 in response to therapy. Four women of each group had abortions. Endometriosis (normal menstrual cycles) was seen in 35% (38%) of the women of each group who failed to respond to therapy with pregnancy. Only 4% of the women who responded to acupuncture or hormone treatment with a pregnancy had endometriosis, and 7% had normal cycles. In addition, women who continued to be infertile after hormone therapy had higher body mass indices and testosterone values than the therapy responders from this group. Women who became pregnant after acupuncture suffered more often from menstrual abnormalities and luteal insufficiency with lower estrogen, thyrotropin (TSH) and dehydroepiandrosterone sulfate (DHEAS) concentrations than the women who achieved pregnancy after hormone treatment. Although the pregnancy rate was similar for both groups, eumenorrheic women treated with acupuncture had adnexitis, endometriosis, out-of-phase endometria and reduced postcoital tests more often than those receiving hormones. Twelve of the 27 women (44%) with menstrual irregularities remained infertile after therapy with acupuncture compared to 15 of the 27 (56%) controls treated with hormones, even though hormone disorders were more pronounced in the acupuncture group. Side-effects were observed only during hormone treatment. Various disorders of the autonomic nervous system normalized during acupuncture. Based on our data, auricular acupuncture seems to offer a valuable alternative therapy for female infertility due to hormone disorders. PMID- 1442163 TI - The effect of combined estrogen/progestogen treatment in women with hyperprolactinemic amenorrhea. AB - Eleven women with hyperprolactinemic amenorrhea were treated with a combined estrogen/progestogen preparation (Loestrin 30) for 3 months as hormone replacement therapy because of estrogen deficiency, with a view to protection against osteoporosis. Serum prolactin levels rose during the 1st month of treatment (p < 0.05) but did not rise significantly further during the 2nd and 3rd months. The levels rose in proportion to pretreatment levels by 28% (median), and fell significantly but not completely during the 1-week treatment-free intervals. After the study period, prolactin values appeared to remain stable in those women who continued longer on treatment, and returned to around pretreatment values in those who stopped. In one woman there was radiological evidence of pituitary tumor growth during treatment. This study shows that estrogen/progestogen treatment in standard contraceptive dosage usually leads to only moderate and non-progressive stimulation of pituitary activity in women with hyperprolactinemic amenorrhea, but occasional excessive growth of a prolactinoma can occur and treatment needs to be monitored. Women with relatively high prolactin levels seem to be at particular risk. Safer variations of estrogen therapy such as lower dosage or combination with a protective low dose of a dopamine agonist should also be considered. PMID- 1442164 TI - Symptom-free interval after triptorelin treatment of uterine fibroids: long-term results. AB - An increasing number of publications document regression of fibroids under treatment with gonadotropin releasing hormone (GnRH) agonists. However, recurrence after stopping treatment regularly counterbalances its benefit. We now report on 28 patients with intramural myomas, treated with triptorelin for 4-6 months and followed for 42-56 months. During or shortly after treatment, six patients entered menopause. In this group, a volume reduction of 71% was achieved and no surgery was needed thereafter. In 22 premenopausal women, a 64% decrease of uterine volumes was obtained at the end of treatment; the long-term reductive effect was 31%. When compared with initial values, a significant decrease was observed at the end of treatment (p = 0.0001) and of follow-up (p < 0.0005). In 13 (of 22) premenopausal patients, surgery was needed after triptorelin treatment for permanent control of fibroids. The remaining nine patients were free of symptoms after 42-56 months, having uteri in situ. These two groups differ significantly in pretreatment uterine volume (p < 0.001) and in reduction rate after therapy (p < 0.01), both parameters being higher in patients who finally needed surgery. In conclusion, triptorelin treatment is definitely beneficial in perimenopausal women and in nearly half of premenopausal women, in whom hysterectomy can be prevented. In the other half, surgery is necessary, despite significant volume reduction. These results need to be corroborated on larger groups of patients. More research is needed to explain different responses to treatment in premenopausal patients. PMID- 1442165 TI - Calcitonin gene-related peptide, the menstrual cycle and premenstrual syndrome. AB - Calcitonin gene-related peptide plasma levels were measured during four different phases of ovulatory menstrual cycles, in eight women suffering from the premenstrual syndrome and in eight controls. No significant fluctuations in calcitonin gene-related peptide levels occurred during the menstrual cycle. Neither were there significant differences in calcitonin gene-related peptide levels between the premenstrual syndrome and control groups. PMID- 1442166 TI - Ovulation induction in in vitro fertilization. PMID- 1442167 TI - Developmental and strain-specific heterogeneity of rat adrenal chromaffin cells recognized by a monoclonal antibody against intact chromogranin B. AB - We have raised a monoclonal antibody (MAB-1E10) reactive with the intact forms but not the processing products of the chromaffin cell vesicle protein chromogranin B (CgB). The antibody recognizes rat and human, but not bovine and chick adrenal chromaffin cells. In addition, MAB-1E10 immunoreactivity was detected in rat PC 12 pheochromocytoma cells and in pituitaries. Several other tissues, including pancreas, small intestine and superior cervical ganglia, which are known to contain CgB in endocrine cells or neurons, respectively, were found not to be reactive with MAB-1E10. Using short-term cultures of dissociated adrenal chromaffin cells from Hannover-Wistar rats, we found that the expression of intact CgB is developmentally regulated. Between embryonic day 19 and postnatal day 40, about 80% of adrenal chromaffin cells--identified by their reactivity with an antibody against the enzyme dopamine-beta-hydroxylase--were found to be reactive with MAB-1E10. The proportion of positive cells subsequently decreased to about 5% at postnatal day 90. In the presence of glucocorticoids, this decrease was reduced to about 45% CgB-positive cells at postnatal day 90. In another rat strain, Sprague-Dawley rats, the proportion of MAB-1E10 immunoreactive chromaffin cells (about 50%) remained constant from birth to adulthood. Our results indicate that CgB is differentially expressed and/or processed in different rat tissues, strains and during development, and furthermore, that expression or processing in rat chromaffin cells might be regulated by glucocorticoids. Intact CgB appears to be a marker for a subpopulation of chromaffin cells, but its function(s) remains to be clarified. PMID- 1442168 TI - Effects of combined pre- and postnatal ethanol exposure (three trimester equivalency) on glial cell development in rat optic nerve. AB - This study evaluated the effects of a combined gestational and 10 day postnatal alcohol exposure (human three trimester equivalency) on the development of glial cells in the rat optic nerve. Pregnant rats were exposed to alcohol via a liquid diet, then their pups were artificially reared and further exposed to alcohol for 10 postnatal days via a gastrostomy fed liquid diet. Control animals, born of pair fed dams, were artificially reared on pair fed isocaloric diets. Optic nerve tissues were prepared for light and electron microscopic studies from animals on gestational days (G) 15 and 20 and postnatal days (P) 5, 10, 15, 20 and 90. There were fewer glial cells per cross-section on day 15 and the cross-sectional areas of optic nerves were smaller on days G20, P15 and P90 in the ethanol exposed animals. There was an alcohol-induced delay in the appearance of immature cells within the oligodendroglia lineage and a decrease in the number of oligodendroglia present at 15 and 20 days, indicating a delay in the maturation of oligodendroglial cells. These effects were compensated for by 90 days. Maturation of the astrocytic cell lineage was generally unaffected by the alcohol although there was evidence of increased numbers of cells in the lineage. There was no consistent indication of alcohol-induced degeneration of glial cells or their organelles. Thus, alcohol exposure for all of gestation and 10 postnatal days in the rat causes a delay in oligodendrocyte maturation but appears to have no long-term effects on the glial cell population of the optic nerve. Such a delay, by contributing to delays in myelin development, could help to explain some of the neurological dysfunctions associated with developmental alcohol exposures. PMID- 1442169 TI - Effects of acetyl-L-carnitine on the survival of adult rat sensory neurons in primary cultures. AB - Acetyl-L-carnitine produces a significant increase in the survival time-course of adult rat sensory neurons maintained in primary cultures up to 40 days. The analysis of our data suggests that 200 microM acetyl-L-carnitine added to the medium, slows down neuronal decay especially in the first 10 days in vitro, sparing a fraction of cells which would otherwise be lost. Patch-clamp recordings from these neurons show that superfusion with acetyl-L-carnitine (100-1000 microM) does not induce any membrane current. In addition an agonist muscarinic effect particularly concerning high-voltage activated calcium channel modulation appears to be ruled out. In conclusion our data favour the role of acetyl-L carnitine in the trophism of sensory neurons in adult rats. In agreement with other in vivo experiments our data reinforce the hypothesis that this substance might be involved in reducing neuronal loss observed in nervous system aging. PMID- 1442170 TI - Synaptic ribbons, spheres and intermediate structures in the developing rat retina. AB - The present study was conducted to investigate the qualitative and quantitative development of synaptic bodies in retinae of Wistar rats during postnatal days 4 28. In addition, the effects of different light regimens and of eye pigmentation on SB numbers were studied. Synaptic bodies were counted and measured in the outer plexiform layer of retinal tissue fixed and processed by routine electron microscopical techniques. At postnatal days 4 and 5, retinae showed only few synaptic bodies. The main numerical development of synaptic bodies occurred between postnatal days 4 and 9, numbers remaining more or less constant thereafter. The intracellular location of synaptic ribbons changed from predominantly cytoplasmic sites to positions at the membrane. In Wistar rats of postnatal day 15 held under a light/dark regimen, synaptic ribbon numbers and lengths were found to be significantly larger at night than at daytime. This was not observed in animals kept under constant darkness. In retinae of a pigmented rat strain, Brown Norway, total numbers of synaptic bodies were similar to those of Wistar rats, whereas the relative proportions of synaptic ribbons and spheres or sphere-like structures, respectively, differed between strains. These results are discussed with regard to synaptic body formation and regulation under the influence of light and eye pigmentation. PMID- 1442171 TI - Correlation between P19 presence and MHC class II expression in human fetal astroglial cells cocultured with HTLV-I donor cells. AB - The possibility of a direct infection of human brain by HTLV-I, has been studied using an in vitro model. Human fetal astroglial cells were cocultivated with irradiated HTLV-I donor cell line MT-2, and assayed for the presence of HTLV-I core protein p19 after 1 week. Fifty-six per cent of GFAP positive astrocytes showed the viral core protein p19 and increased expression of Class II MHC antigens. Electron microscopy of astroglial cells exposed to HTLV-I revealed the presence of vacuoli-like structures containing viral core protein p19. Cell intermediate filament cytoskeleton was also disorganized. Even if this study does not provide direct evidence for virus replication inside astroglial cells, all these findings suggest that HTLV-I can indeed enter the cell and exert a cytopathic effect. Therefore the results of the present study are consistent with the hypothesis that astroglial cells could be involved in demyelination processes occurring in the HTLV-I associated neurological disorders, such as human associated myelopathy and tropical spastic paraparesis. PMID- 1442172 TI - Transcriptional induction of H2 (class I) antigens and beta 2 microglobulin by interferon-gamma in interferon-sensitive and interferon-resistant Friend leukemia cells. AB - The effect of interferons (IFNs) type I (alpha/beta) and type II (gamma) on the stimulation of H2-Dd (class I) and beta 2 microglobulin genes transcription was analysed in IFN-sensitive (w.t.) and IFN-resistant Friend erythroleukemia cells (FLC). Type I IFN enhances the expression of H2-Dd and beta 2 microglobulin genes in w.t. FLC but does not modulate the expression of these genes in clones resistant to IFN-alpha/beta. IFN type II treatment of w.t. and IFN-alpha/beta resistant cell lines results in an increased expression of H2-Dd and beta 2 microglobulin genes, while being ineffective in the cell clone resistant to both types of IFNs. In this cell system the effect(s) of IFN type II is in part mediated by the induction of IFN-beta. The results reported in the present paper suggest that the IFN-gamma is able per se to increase the expression of H2-Dd and beta 2 microglobulin genes; since a reduced but clearly evident stimulation of the expression of these genes was observed in the FLC clone totally resistant to type I IFN. PMID- 1442173 TI - Interferon-caused alterations of poly(A)-polymerase activity levels in established cell lines. PMID- 1442175 TI - Mechanoluminescence: an assay for lymphocyte analysis in neoplasia. AB - We have studied the mechano-electrochemical activation of optical emission (mechanoluminescence, ML) from the surface of lymphocytes. In C57BL/6 mice with B16 melanoma at the terminal stage of tumour growth and after immunotherapy with thymic agents, there is a correlation between light emission and the value of lymphocyte surface charge and titres of thymic serum factor (FTS). PMID- 1442174 TI - A macrophage derived blastogenic factor -MBF- induces cytokines and cytotoxic effectors in human peripheral blood mononuclear cells. AB - A soluble macrophage-derived blastogenic factor, previously reported as MBF, is secreted from macrophages activated with galactose oxidase. It was previously shown that MBF is able to induce IFN-gamma production and proliferation of T lymphocytes. In this study we found that MBF is able to induce in human peripheral blood mononuclear cells (PBMC) production of interleukin 1 (IL-1) beta, interleukin 2 (IL-2) and tumor necrosis factor (TNF) alpha and generation of MHC-unrestricted cytotoxic activity. The induction of killer cells is likely to rely on IFN-gamma production in that in PBMC treated with a monoclonal antibody (Mab) against IFN-gamma, the MBF induced cytotoxic activity was drastically reduced. A comparison of MBF induced cytotoxic effectors with those induced by IL-2 showed that both cytotoxic effectors pertain to NK lineage, in that they were CD3- and CD16+. On the contrary, the precursors of MBF and IL-2 induced killer cells were different; MBF cytotoxic precursor cells were highly sensitive to L-Leucine methyl ester (Leu-OME), a drug able to eliminate monocytes and NK cells, whereas IL-2 cytotoxic precursors were unaffected by this drug. PMID- 1442176 TI - Luminescence from the yeast Candida utilis and comparisons across three genera. AB - Weak luminescence was detected from oxygenated liquid cultures of the yeast Candida utilis during two stages of its growth cycle. The first period of emission occurred during the exponential phase of growth and comprised an ultraviolet band (270-390 nm; ca 19 photons s-1 cm-2 of culture surface) and a visible band (450-620 nm; ca 68 photons s-1 cm-2). The second period of emission occurred late in the stationary phase of growth and was comprised almost entirely of a visible region band (450-620 nm; 6.8 x 10(2) photons s-1 cm-2). No luminescence was observed when the yeast was grown anaerobically. These observations are compared with those previously obtained for two other yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe. The ratios of the intensities of the blue/red emissions in the stationary phase luminescences correlated with the ratio of the saturated/unsaturated lipid content for the three yeasts. This result provided further support for the claim that the stationary phase luminescence arises from the reactions associated with lipid peroxidation. A number of previously suggested sources of the exponential phase luminescence are discussed and rejected. Oxidative side reactions accompanying protein synthesis remain a possible source of that emission. PMID- 1442177 TI - Bioluminescence and chemiluminescence literature--immunoassays and protein blotting assays. PMID- 1442178 TI - [Assessment of iron requirements during treatment of anemia with recombinant human erythropoietin in patients with chronic renal insufficiency under hemodialysis]. AB - Iron deficiency occurs often in patients with recombinant human Erythropoietin (rhEPO) therapy in chronic renal failure (CRF) associated anemia. We have studied 10 patients with CRF on regular hemodialysis (HD), female = 8, male = 2, average age = 49 [32 to 72], time on HD 44.2 +/- 25.0 months. Before starting rhEPO, the mean hemoglobin value was 7.36 +/- 1.29 gr/dl, the mean ferritin 695.4 +/- 276.0 ng/ml, the mean serum iron 160.3 +/- 49.5 micrograms/dl and the mean transferrin saturation 55.3 +/- 12.6%. Transfusional requirements in the 12 months Pre-rhEPO were 10.9 +/- 3.2 units. The rhEPO dose level was 80 U/kg body weight (3 times a week, after HD) in the Correction Period (mean time = 46.7 +/- 18.6 days), being reduced afterwards in order to remain target Hb stable between 10 and 11 gr/dl. Iron deficiency was detected (transferrin iron saturation less than 16% or serum ferritin less than 30 ng/ml) in 5 of the 10 patients. Patients have been divided into two Groups (GI--patients which developed iron deficiency; GII--patients which remained iron replete). There were no significant differences between GI and GII in the serum iron, transferrin and transferrin saturation values of the Pre-rhEPO. Serum ferritin in the Pre-rhEPO was lower in GI than GII (GI = 489.2 +/- 23.6 ng/ml; GII = 901.6 +/- 96.4 ng/ml; p less than 0.01). Falls in the transferrin iron saturation during the Correction Period and 3, 6 and 12 months and in the serum ferritin at 3, 6 and 12 months versus Pre-rhEPO have occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442179 TI - [Skin pathology in kidney transplant recipients]. AB - Since 1990, 82 unselected renal allograft recipients were evaluated in order to establish the incidence of cutaneous disorders. This pathology was related to the period of immunosuppression according to time of transplantation: 0-3 months; 3 12 months; 12-36 months and beyond 36 months. Most of them were on triple immunosuppression (cyclosporine A, azathioprine and prednisone)--(51); Twenty-two also associated anti-timocyte globulin five days after transplantation; 7 were on Azathioprine and Prednisone and two of them associated Cyclosporine with Prednisone. Iatrogenic manifestations were the most common (80.5%) followed by infections in 63.4% and pre-malignant and malignant cutaneous lesions in 13.4%, other types of manifestations were found in 20.7% of patients. A significant incidence of pre-malignant and malignant lesions confirms other reports, making a dermatological surveillance advisable. PMID- 1442180 TI - [Carcinoma of the lung. Review of a caseload of 12 years at a service of internal medicine]. AB - The authors present a retrospective study of medical records of patients with lung cancer, admitted at the Service 1 of Internal Medicine of Santo Antonio dos Capuchos Hospital during a 12 year period (1978-1989). Of the 112 selected patients, 50% had histologic diagnosis, the remaining had strong clinical radiographic, endoscopic and/or autopsic evidence of pulmonary malignancy or malignant cytology in sputum, bronchial secretions or pleural fluid. The clinical symptoms and means of diagnosis are presented and the advanced stage of the disease, at admission, the problems concerning the histologic diagnosis and the high mortality rate (55.4%) are emphasized. PMID- 1442181 TI - [Neurologic manifestations of Behcet disease. Review of the caseload of the Neurology and Dermatology services at the Santa Maria Hospital]. AB - Neurological involvement in a series of patients with Behcet's disease, evaluated at the Departments of Neurology and Dermatology, St. Maria Hospital is reported. Meningoencephalytic or encephalytic were the most common clinical forms, while headache, cerebellar and pyramidal signs were the most prevalent symptoms/signs. On follow-up (range 2-13 years) the majority of the patients had either a progressive or a remitting-progressive course. Magnetic ressonance imaging was the most valuable method of detecting central nervous system lesions. PMID- 1442182 TI - [Incidence of and mortality from malignant tumors inthe municipality of++Vila Nova de Gaia: 1981-1987]. AB - Data from the population based Cancer Registry of Vila Nova de Gaia for the 1981 1987 period are presented. Cancer is becoming a disease increasingly frequent in Portugal, causing progressively higher mortality rates. Population and geographic characteristics of Vila Nova de Gaia country is presented. Information sources of this Registry are hospitals, pathology labs, Health Authority files and death certificates. Net (229.2, 216.6) and standardized for european population (369.9, 245.9) incidence rates are presented for respectively men and women. Comparisons with registries from other countries (e.s.) are made. PMID- 1442183 TI - [Diagnosis of Lepore hemoglobinopathy with DNA analysis]. AB - We illustrate the application of recombinant DNA methods (namely Southern blotting) for the genotype diagnosis of haemoglobin Lepore Boston: the use of the restriction endonucleases PstI and XbaI along with a beta globin gene specific probe make it possible to detect a deletion of approximately 7kb which typically characterizes the delta beta Boston gene. The impact of using such methods in the prenatal diagnosis of major haemoglobinopathies is discussed. PMID- 1442184 TI - [Chronic disease, the chronic patient and his family. Psychosocial impact of diabetes mellitus]. AB - Concerning a revision about the mutual influence between the diabetes, the diabetic and his family, the author reviews the literature about the psychosocial area of the Family Physician content's work. It is also confirmed the high prevalency of the chronic disease and the importance of the family ecosystem, not only as support but also as problem to the bearing person of such type of disease. Studies of chronic disease indicate that family dysfunction is associated with poor health outcomes. The areas which more and better have been studied in this scope are reviewed. Thus, having as backdrop the diabetes management, the family's diabetic influence in general is reviewed, as well as the parental attitudes, the family organization and the family life events. Finally, the health care team role is reviewed and particulary the role of the family physician in the management of this type of patients. It is pointed out, as example of the Family Medicine specific contribution, the improving cooperation with medical treatment from the diabetic. PMID- 1442185 TI - [Research on psychosomatic disease. Various theoretical and methodologic aspects]. AB - This article mentions ther present main lines of psychosomatic research either in what concerns the elimination of the concept of psychosomatic illness, or in what concerns its etiological understanding of the peculiar ways of therapeutic approach. We specify some methodological problems resulting from using several instruments to collect data and measure them. We analyse the theoric relevance of the constructs: depressive equivalents and, specially, the alexithymia one. Starting from the consensual phenomonological description of this construct, we explain its psychodynamic understanding, its neurophysiologic basis and sociocultural determination. We question the relationship between alexithymia and psychosomatic illness. We point out the pertinency of its utilization as a risk or maintainance factor and the possibility of its modelling by ambiance factors. We clarify the main heuristic contributions of this construct to psychosomatic investigation and we analyse, critically and concisely, the validity and fidelity of some instruments of measure built to measure it. It is necessary to pay prior attention to psychosomatic investigation in the health area. We propose lines of investigation to be developed in our country that should have a multidisciplinary perspective. PMID- 1442186 TI - [Gastrinoma localized in the pylorus in a patient with recurrent peptic ulcer]. AB - We report a clinical case of a woman, 56 years old, with a history of duodenal ulcer and esophagitis, under medication with H2 receptors blockers during 3 years. Plasma basal gastrin was near normal levels. A stimulation test with secretin was compatible with gastrinoma. CT scan and selective angiography didn't localize the tumor. At laparotomy we found a pyloric nodule that prove to be the gastrinoma. Eighteen months after surgery the patient is asymptomatic and with a normal endoscopic examination and secretin stimulation test. PMID- 1442188 TI - [I National Congress of echography. Final echoes]. PMID- 1442187 TI - [Neodymium--Yag laser in the recanalization of arterial occlusions]. AB - Failure of the guide-wire to recanalize some arterial total occlusion does not preclude balloon angioplasty. Nowadays there are recanalization devices such as the mechanical atherectomy and Lasers. The following report describes the successful use of the Nd: YG Laser in the recanalization of a common iliac artery total occlusion in a patient with claudication, rendering possible balloon angioplasty and a Palmaz Stent implantation, which is the first case performed in our country. PMID- 1442189 TI - [Ileoanal pouch for the treatment of adenomatous polyposis and ulcerative colitis -clinical and functional results]. AB - The results of the first 9 patients with proctocolectomy and ileal pouch operated on between 1983 and 1990 were analysed. This procedure was carried out in 8 patients with adenomatous polyposis. Three of these patients had an associated rectal cancer and one a degenerated sigmoid polyp. One patient had ulcerative colitis and was previously submitted to a colectomy related with perforated fulminant colitis. Three types of pouches were constructed: 3 S, 3 J and 3W, all with a temporary ileostomy. A circular stapler was used in 2 cases for ileoanal anastomosis. Three postoperative complications were observed: two patients with pouchitis during the presence of a diverting ileostomy and an ileal fistula following ileostomy closure, all medically treated. Clinical and functional results were evaluated 1 to 7 years after the procedure. The average daytime stool frequency was 4 with 1 nocturnal. All patients indicated normal continence. One patient had her professional life affected due to the increased number of defecations. Differences in the clinical results of the patients with S, J and W pouches were not statistically different. The functional results expressed as median and range were as follows: resting and pressure 45 cm H2O (20-60), voluntary anal pressure 70 cm H2O (34-120), compliance 3.70 ml/cm H2O (1.14 11.40), maximal tolerated volume (MTV) 320 ml (110-48) and threshold volume 95 ml (40-170). The MTV values of the groups with J and W pouches were 190 ml (180-200) and 370 ml (340-480), respectively (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442190 TI - [Spinal brucellosis. 4 years of experience]. AB - The Authors retrospectively studied 17 patients who have been admitted to the Infectious Diseases Clinic of Coimbra University Hospital during a four year period and whose final diagnosis was brucellar spondylitis. Clinical, epidemiological, laboratory and imaging features are analyzed, as well as those related to the therapeutic schedules and outcome. Females were more often affected (70.58%) and the mean age was 53.35 +/- 13.82 years. Lumbar spine was most frequently involved and an unusual elevated incidence of paravertebral soft tissue swelling was noticed (23.52%). Two patients were also suffering from neurobrucellosis (11.76%). The preferred therapeutic schedule was rifampin and doxycycline and surgery was performed in one patient. Finally, several comments are made regarding basically the incidence, laboratory and imaging diagnosis, therapeutic aspects and evolution of the disease. The imaging similarities and differences between tuberculous, pyogenic and brucellar spondylitis are briefly approached. PMID- 1442191 TI - [Surgical and trauma patients in a medical intensive care unit]. AB - OBJECTIVE: to characterize and to assess in terms of severity the surgical and trauma patients admitted to a medical intensive care unit (ICU). DESIGN: retrospective study base on clinical records and the ICU computerized database. SETTING: the medical ICU of a tertiary hospital. RESULTS: of the 2468 patients admitted to the ICU in 1989, 289 (11.7%) were surgical or trauma ones. The more frequent reasons for admission were: the need for mechanical ventilation, metabolic problems, and depression of consciousness. Of these 289 patients, 48.1% required mechanical ventilation, 14.9 hemodialysis; 4.8% had a pulmonary artery catheter inserted. Mean APACHE II, TISS and MOF scores were high (20.09 +/- 9.29, 24.17 +/- 11.45 and 5.4 +/- 3.59); they were determined in 79.2, 88.2 and 43.9% of patients respectively. Both APACHE and TISS scores were correlated with mortality. When compared with medical patients, surgical/trauma ones although younger (52.9 +/- 20.7 years versus 55.9 +/- 20.2, p = 0.00152), had a longer mean stay in the ICU (7.63 +/- 12.7 days v. 3.64 +/- 7.61, p = 0.0001), and a higher mortality (also in the ICU) (28.7 v. 16.7, p = 0.0005. COMMENTS: these are seriously ill patients, who are frequently referred to the ICU in late stages of clinical evolution. We propose they should be closely followed, from the earliest possible stage, by medical-surgical teams, in order to benefit from a multidisciplinary approach. PMID- 1442192 TI - [Comas in the emergency room of a central hospital]. AB - The aim of the present prospective work was to study the etiologic diagnosis and prognosis of the comatose patients for whom a neurologic examination is requested. It included 148 consecutive cases admitted to the emergency room of a general hospital. Coma was caused by supratentorial lesions in 38%, subtentorial lesions in 10%, diffuse or metabolic brain dysfunction in 49%, and psychiatric disorder in 1% of the patients. CT scan was the most valuable ancillary exam, modifying the initial etiologic diagnosis in 42% of the cases on whom it was performed. Seventy percent of the patients died. Coma caused by structural lesions had a worse outcome than coma caused by diffuse or metabolic brain dysfunction (intoxications excluded), and this type of coma had a worse outcome than drug-induced coma. The presence of anisocoria, the number of brainstem reflexes present and the pattern of motor response, as well as the Glasgow Coma Scale score, predicted the outcome. PMID- 1442193 TI - Percutaneous splenic embolization of the splenic artery in the treatment of hypersplenism. AB - Percutaneous splenectomy was performed in 6 patients with hypersplenism. Peripheral blood cell counts improved in 5 of the patients. The authors review the indications, technique and complications of percutaneous splenic embolization. It is concluded that medical splenectomy is an effective method particularly to alleviate symptoms of hypersplenism. PMID- 1442194 TI - [Solar radiation--physicochemical aspects]. AB - The solar radiation spectrum and the properties of its components are studied in the present paper. The history of the sun rays before reaching earth surface is analysed. A simplified analysis of the interaction mechanisms of these components with molecules, the energy absorption capabilities of the latter and the expected biological consequences are considered. Special emphasis are given to the properties of ultra-violet and infra-red radiations and their production considered. PMID- 1442195 TI - [Anorexia nervosa and a psychosomatic investigation]. AB - The paper begins with a revision of diagnostic criteria of Anorexia Nervosa (AN), stressing the importance of early diagnosis and transitional forms between AN and Bulimia Nervosa. A retrospective study of 13 female patients with AN, treated during 1990 in Lisbon Psychiatric University Clinica (Hospital de Santa Maria, Lisboa) is then described. The Authors outline some common characteristics of the sample, many difficulties in the early relationship mother-child, shown by maternal unsatisfaction on feeding the baby and with changing of food. Concluding, the Authors point out some directions for eating disorder's investigation, starting with a multidisciplinary work including biological and cultural factors and understanding of individual development and family dynamics. PMID- 1442196 TI - [Apropos of ileoanal anastomosis in ulcerative colitis and intestinal polyps]. PMID- 1442197 TI - [Pulmonary emphysema in a patient with Turner's syndrome]. AB - Turner's Syndrome was first described in 1938 by Henry Turner and has an incidence of 1:3000 live female births. The authors present an unusual case of a 48-year-old woman with late diagnosed Turner's Syndrome. Whose karyotype was (46,X,i(Xq)), associated with a pulmonary emphysema and pulmonary hypertension. The case and the methods of study are presented. Some aspects of this case, namely the hypothesis of an association between the pulmonary emphysema and Turner's Syndrome are discussed. PMID- 1442198 TI - [Emphysematous cholecystitis]. AB - Emphysematous cholecystitis (EC) is a rare and dramatic disease that requires prompt therapeutic procedures. The authors report a case of a 70-year-old-woman, admitted to the Intensive Care Unit for Infectious Diseases of the Santa Maria Hospital, with the diagnosis of EC. The literature on EC is also reviewed. PMID- 1442199 TI - [Limitations and perspectives of teaching and research in basic sciences at the Portuguese Faculties of Medicine]. AB - Well known difficulties of teaching and research lived by basic sciences of the medical school curriculum in Portugal are becoming desperate. Two main problems deserve major concern and urgent solutions: firstly, the recruitment and continuing formation of motivated candidates for teaching and/or research in those areas; secondly, the establishment of adequate economic support that makes those careers in basic teaching and research attractive, along with the provision or creation of the necessary support for both activities. Specific administrative and financial solutions are required from the government, in order to foster a realistic future in the preclinical areas of the medical curricula. PMID- 1442200 TI - Change in bone mass immediately before menopause. AB - A group of 75 healthy women nearing menopause were entered into a longitudinal study of bone mass and bone cell function. All were at least 46 years, were still menstruating, and had premenopausal levels of follicle stimulating hormone (FSH) and estradiol (E2). Bone density measurements of the spine (dual-photon absorptiometry, DPA) and total-body (DPA) and forearm (single-photon absorptiometry, SPA) were made at 6 month intervals along with measurements of FSH and E2 over an average of 2.04 +/- 0.45 years. The annual rate of change in bone mass was determined for each individual by regressing the bone mass measurement at each site at the time of observation. The slopes were pooled, and the percentage annual change was calculated as the mean slope divided by the initial mean bone mass value. The mean rates of change in bone mass were calculated with and without weighting by length of observation. No meaningful differences in the results were seen in the weighted values compared to the unweighted values, and none of the sites showed a slope significantly different from zero. Demonstrated reproducibility and sample size provided sufficient power to detect annual weighted rates of change of 0.81% for spine BMC, 0.69% for spine BMD, 1.31% for forearm BMC, 1.55% for forearm BMC/BW, and 1.09% for total body bone mineral. We conclude that if changes in bone mineral are occurring in women at this age, they are substantially less than 1%/year for spine and not much more for the forearm or total skeleton. PMID- 1442201 TI - Enhancement of osteoinduction by vitamin D metabolites in rachitic host rats. AB - Diaphyseal bone from normal Sprague-Dawley rats was delipidated in chloroform methanol and demineralized in 0.6 N HCl at 4 degrees C. The bones were then implanted for 7-28 days into rats made rachitic by a low-phosphate, vitamin D deficient diet (VDP-) for 3 weeks. Bones from VDP- and normal rats were also implanted into normal hosts. When normal rats were used as the host environment, a consistent sequence of cartilage induction and bone formation was observed. Demineralized rachitic bone (RB) implanted into normal host rats resulted in cartilage and bone induction similar to that seen for normal bone (NB) implants. Transmission electron microscopy of RB in normal hosts revealed morphologically normal chondrocytes and cartilage matrix with normal mineralization. In contrast, implantation of NB in VDP- hosts resulted in delayed chondrogenesis and lack of calcification. Furthermore, similar results were observed when RB was implanted into VDP- hosts. Treatment of VDP- hosts with either 1 alpha-hydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 did not accelerate the sequential appearance of precartilage or cartilage. However, 24,25-(OH)2D3 administered alone or in combination with 1 alpha-OHD3 significantly increased the amount of calcified cartilage observed at 2 weeks postimplantation compared to implants from either untreated VDP-hosts or those treated only with 1 alpha-OHD3. New bone formation was observed at 4 weeks postimplantation in all vitamin D-treated groups as determined by von Kossa staining or direct electron microscope examination. There was no apparent difference in the quantitative or qualitative bone formed within the various vitamin D-treated groups. Serum calcium and phosphorus levels were lower and alkaline phosphatase levels were higher in VDP- hosts compared with normal animals or those treated with vitamin D metabolites. The results of this study show a reduction in the capacity of progenitor cells in VDP- rat hosts to respond to osteoinductive factor(s). This impaired response appears to be corrected by vitamin D metabolites. PMID- 1442202 TI - Evidence for the formation of a complex between osteopontin and osteocalcin. AB - We hypothesize that the mechanisms governing bone formation and remodeling involve the assembly of some of the components of the extracellular matrix into supramolecular complexes. We have examined the associations of osteopontin (OPN) with other proteins isolated from demineralized rat long bones. Three ligand binding techniques were used to demonstrate the formation of complexes between osteopontin and osteocalcin (OCN). Using gel overlay assays, the binding between soluble 125I-OPN and OCN immobilized in acrylamide gels was visualized. Competition for 125I-OPN-OCN complexes was demonstrated when unlabeled OCN enriched bone extract was included in gel overlay solutions. Also, gel overlay assays showed 125I-OCN binding to OPN. Saturable binding was shown in solid-phase filter binding assays, which yielded an equilibrium binding constant of moderately high affinity (approximately 10(-8) M). Specificity of OPN-OCN complex formation was confirmed by measuring binding in the presence of unlabeled OPN and OCN versus a bone-localized serum protein, alpha 2HS-glycoprotein. Finally, the formation of soluble complexes were demonstrated in a modified Hummel-Dreyer gel filtration assay. These results indicate that OPN and OCN form complexes in vitro. The possible functions of OPN-OCN complexes in osteoclast recruitment and attachment are discussed. PMID- 1442203 TI - Advantages of peripheral radiogrametry over dual-photon absorptiometry of the spine in the assessment of prevalence of osteoporotic vertebral fractures in women. AB - Since osteoporosis develops in most postmenopausal women and is probably the most important single factor in the pathogenesis of osteoporotic fractures of the spine, hip, and wrist (and at other sites), methods suitable for mass screening should be developed. In this study of 97 women aged 24-79, measurements of the lumbar spine mineral content by dual-photon absorptiometry (DPA) were compared with the summed combined cortical thickness measurements from radiographs of the radius and metacarpal II (MR). There was good correlation between the two methods (r = 0.90). The correlation of age with MR was higher than with DPA. The correlation of years postmenopause was significant with MR but not with DPA. Taking the -2 SD level of the premenopausal means to be previously established vertebral fracture thresholds, 24% of the DPA measurements, but no MR measurements in patients with vertebral compressions, were above the fracture threshold. Since MR measurement requires taking only two small plain radiographs using ordinary x-ray equipment, it is concluded that this less expensive method is better suited to screening for osteoporotic vertebral fracture risk in postmenopausal women than DPA. PMID- 1442204 TI - Relationship between the location of osteoblastic alkaline phosphatase activity and bone formation in human iliac crest bone. AB - It is not feasible to use in vivo tetracycline double labeling to study bone formation in biopsies taken during the emergency fixation of fractures. We therefore compared the trabecular localization and extent of osteoblastic alkaline phosphatase (AP) perimeters with tetracycline and osteoid perimeters in iliac crest biopsies from 7 women with postmenopausal osteoporosis and 13 women without metabolic bone disease. Fresh biopsies were chilled to -70 degrees C, and triplicate serial unfixed undecalcified cryostat sections were cut and reacted for AP, stained for osteoid, or mounted unstained. At individual remodeling sites, the mineralizing perimeter (M.Pm) was measured as the extent of a double or single label accompanied by greater than or equal to 1 lamella of osteoid and greater than or equal to 1 lamella of mineralized matrix between the mineralization front and the adjacent label. Osteoid perimeters (O.Pm) and AP perimeters (AP.Pm) were also measured. In each biopsy there was good agreement between the location of AP and bone formation (kappa statistic, range 0.71-1.0). The overall sensitivity and specificity of AP as an indicator of the location of bone formation were 0.963 and 0.902, respectively. At the level of the basic multicellular unit, in those samples in which greater than 3 active BMUs were found, there was (1) significant positive correlation between the M.Pm and both AP.Pm and AP-positive O.Pm (except 1 patient) and (2) no significant difference between the M.Pm and AP-positive O.Pm (17 of 18 patients and 18 of 18 patients at the tissue level).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442205 TI - Maintenance of cancellous bone connectivity in primary hyperparathyroidism: trabecular strut analysis. AB - We previously demonstrated an increase in cancellous bone volume and trabecular number in patients with mild primary hyperparathyroidism (PHPT). To test the hypothesis that this increase is due to preservation of cancellous bone architecture, we conducted a trabecular strut analysis using a new method that measures trabecular connectivity. Iliac crest biopsies from 37 patients with PHPT, 14 men (28-68 years) and 23 women (26-68 years), were examined histomorphometrically and compared to cadaveric samples from 24 age-matched subjects, 17 men and 7 women. Two-dimensional indices of cancellous structure- node number (N.Nd), terminus number (N.Tm), node to node (Nd.Nd), node to terminus (Nd.Tm), and terminus to terminus (Tm.Tm) strut lengths, and total strut length (TSL)--were measured and the ratio of node number to terminus number (N.Nd/N.Tm) calculated. TSL, N.Nd, and Nd.Nd were significantly higher in patients than in controls. TSL and Nd.Nd, but not N.Nd or Nd/Tm, decreased significantly with age in PHPT, indicating that age-related bone loss in PHPT occurs without significant loss of trabecular connectivity. Two-dimensional indices reflecting connectivity or the amount of bone, that is, N.Nd, Nd.Nd, N.Nd/N.Tm, and TSL, correlated positively with cancellous bone volume (BV/TV) and trabecular number (Tb.N) and negatively with trabecular spacing (Tb.Sp) in both PHPT and controls. Trabecular thickness (Tb.Th) correlated positively with Nd.Nd and Tb.N and negatively with Tm.Tm in PHPT but not in controls. The present data show that in PHPT there is not only greater cancellous bone volume and trabecular number but preserved trabecular connectivity as well. The data further support the hypothesis that in PHPT cancellous bone architecture is maintained. PMID- 1442206 TI - Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta. AB - Extracellular matrix proteins synthesized by bone cells isolated from 16 patients with different forms of osteogenesis imperfecta (OI) were analyzed in vitro. Specific components of the extracellular matrix by OI and age-matched cultures were investigated by steady-state radiolabeling followed by quantitation of label into specific proteins and comparison of OI cultures to those of age-matched controls. The in vitro proliferation of OI bone cells was found to be lower than that of control cells. In seven patients, abnormalities of the alpha 1(I) and/or alpha 2(I) chains of type I collagen were detected by gel electrophoresis. In two of these patients, the mutations in the COLIA1 and COLIA2 genes have been previously identified. Although the amount of total protein synthesized by the cells in culture was the same for OI bone cells and age-matched control cells, OI bone cells showed a significantly reduced synthesis of not only collagen but also other bone matrix glycoproteins. The synthesis of osteonectin (SPARC/BM40) and three proteoglycans [a large chondroitin sulfate proteoglycan, biglycan (PGI), and decorin (PGII)] was found to be decreased in OI cells. The reduction was most pronounced at the developmental age at which these macromolecules reach maximal levels during normal development. PMID- 1442207 TI - Nitroblue tetrazolium reduction and bone resorption by osteoclasts in vitro inhibited by a manganese-based superoxide dismutase mimic. AB - Oxygen-derived free radicals are produced by osteoclasts. Oxygen radical formation occurs at the osteoclast/bone surface interface. This location next to bone implies that oxygen radicals, including but not limited to superoxide, are needed for bone resorption. Compounds that scavenge superoxide are being developed as pharmaceutical agents to inhibit the damaging effects of oxygen radical formation on tissues. One such scavenger is the Desferal-manganese complex (DMnC). DMnC reduced the amount of formazan staining produced by the interaction of oxygen radicals with nitroblue tetrazolium (NBT) in both individual mouse calvarial osteoclasts in tissue explants and isolated osteoclasts. As a result of the reduced concentrations of oxygen radicals, DMnC inhibited bone resorption by calvarial explants and isolated osteoclasts. Superoxide dismutase (SOD) inhibited NBT reduction and bone resorption by isolated osteoclasts but to a lesser degree than DMnC. Inhibition of bone resorption in the isolated osteoclast system increased in parallel to the concentration of DMnC in cultures. Desferal without Mn had no effect on bone resorption by isolated osteoclasts. These results support the hypothesis that osteoclasts produce oxygen radicals as part of the process of bone resorption. PMID- 1442208 TI - Qualitative defects in natural killer cell function in ia osteopetrotic rats. AB - Recent studies have provided evidence that cells of the immune system and their associated cytokines function in the regulation of bone turnover. The incisors absent (ia) osteopetrotic rat represents a model in which a defect in the immune system and bone resorption can be studied. Osteopetrosis in the ia rat is characterized by a generalized excess accumulation of bone as a result of reduced bone resorption by defective osteoclasts that lack a ruffled border and the ability to exocytose their osteolytic enzymes. Previous attempts to identify associated defects in the ia immune system have proven unsuccessful; ia rats demonstrate normal delayed hypersensitivity, mitogenic activity, and macrophage function. Inasmuch as the skeletal manifestations of the ia mutation may be the result of a defect in exocytosis, related defects may be evident in immune cells utilizing exocytosis of granules or enzymes for their cytolytic function. Natural killer (NK) cells function by such a mechanism. Therefore, these studies were undertaken to evaluate the natural immune system in ia rats. NK activity assessed by 51Cr release assays was significantly reduced in ia animals compared to normal littermates. Mononuclear cells isolated from the peripheral blood of ia rats revealed a significantly greater percentage of large granular lymphocytes than normal littermates. Comparison of NK cell phenotypes using two phenotypic parameters for NK cells (OX8+, OX19- cells and 3.2.3+ cells) revealed that the mononuclear isolates of spleen and peripheral blood of mutant animals had significantly greater percentages of OX8+, OX19- and 3.2.3+ cells than normal controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442209 TI - The bisphosphonate, alendronate, prevents bone loss in ovariectomized baboons. AB - We examined the effect of the amino bisphosphonate alendronate, administered IV every 2 weeks at 0.05 and 0.25 mg/kg for 1 year, on bone loss and parameters related to bone metabolism in ovariectomized baboons. Relative to non-OVX animals, the OVX baboons experienced increased bone turnover, reflected in biochemical and histomorphometric measurements, and bone loss assessed by dual beam absorptiometry in the lumbar spine, which was similar to changes observed in ovariectomized women. Alendronate treatment maintained all parameters of bone turnover at control (nonovariectomized) levels and prevented the bone loss in a dose-dependent manner. We concluded that ovariectomized baboons offer a suitable model for the bone changes observed in ovariectomized women and that these changes can be prevented by sustained administration of an appropriate dose of this aminobisphosphonate. PMID- 1442210 TI - Effect of fluoride on bone and bone cells in ovariectomized rats. AB - To evaluate whether treatment with a mitogenic agent may increase bone formation and bone mass in osteopenia induced by estrogen deficiency, we determined the effect of oral fluoride treatment on bone and bone cells in ovariectomized rats. Sodium fluoride (NaF) was administered to 3-month-old ovariectomized rats 1 day after ovariectomy (OVX) for 1, 3, and 6 months. NaF was given in drinking water at the dose of 1 mg/kg body weight per day. Fluoride administration led to a partial prevention of the bone loss induced by OVX as shown by histologic analysis of tibial metaphysis and by evaluation of femoral calcium content. These beneficial effects of fluoride were more striking at early time points (1 and 3 months postovariectomy) than after 6 months of treatment. The increase in trabecular bone volume in OVX rats treated with fluoride was associated with a rise in the osteoblast surface, which was increased by 60, 72, and 235% at 1, 3, and 6 months postovariectomy compared to untreated OVX rats. In OVX rats and in sham-operated rats plasma osteocalcin was increased in correlation with the osteoblast surface. However, these two parameters were not correlated in OVX rats treated with fluoride. The heat-labile bone-specific alkaline phosphatase in plasma was decreased in OVX rats treated with fluoride compared to OVX rats, suggesting that both the number and the activity of osteoblasts were affected by NaF treatment. To examine the effect of fluoride on the osteocalcin production and the proliferative capacity of bone cells, osteoblastic cells were isolated by collagenase digestion from the bone surface of tibia in treated and untreated OVX rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442211 TI - Localization of parathyroid hormone-related protein mRNA expression in breast cancer and metastatic lesions by in situ hybridization. AB - Parathyroid hormone-related protein (PTHrP) has been identified immunohistochemically in 60% of breast carcinoma and in 92% of breast cancer metastases in bone. To establish whether the localization of the PTHrP antigen reflects protein synthesis and also to investigate the role of PTHrP in metastatic disease, as part of an ongoing study, we used in situ hybridization to study the localization of PTHrP mRNA in a retrospective series of primary breast tumors and their metastatic lesions. Paraffin sections of 17 primary and 26 metastatic lesions, 11 of which were in bone, were available for the study: 10 of the 17 (59%) primary lesions, 8 of 11 (73%) breast cancer metastases to bone, and 3 of 15 (20%) metastases to non-bone sites showed specific localization of PTHrP mRNA. These findings establish that PTHrP is commonly synthesized by primary breast cancers and support previous immunohistochemical studies reporting a higher incidence of PTHrP-positive tumor cells in skeletal metastases than in nonskeletal metastases. PMID- 1442212 TI - Disodium 1-hydroxy-3-(1-pyrrolidinyl)-propylidene-1,1-bisphosphonate (EB-1053) is a potent inhibitor of bone resorption in vitro and in vivo. AB - The ability of the new nitrogen-containing bisphosphonate disodium-1-hydroxy-3-(1 pyrrolidinyl)-propylidene-1,1-bisphosphona te (EB-1053) to inhibit osteoclastic resorption was examined in vitro and in vivo. Results were compared to those obtained with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (pamidronate or APD). In vitro, when tested in osteoclast precursor-dependent systems (fetal mouse metacarpals and a coculture system), EB-1053 suppressed 45Ca release effectively and was found to be about 10 times more potent than pamidronate (ED50 = 2.5 x 10(-7) versus 2.5 x 10(-6) M, respectively). The EB-1053-inhibited osteoclastic resorption could be reversed by treatment with parathyroid hormone (PTH). In vivo, daily subcutaneous injections of EB-1053 to young growing rats for 7 days increased metaphyseal bone mass in tibiae dose dependently. In these experiments EB-1053 was about 50 times more potent than pamidronate. These studies show that EB-1053 is a very potent bisphosphonate that has potential use in the treatment of skeletal disorders. PMID- 1442213 TI - Development expression of bone sialoprotein mRNA in rat mineralized connective tissues. AB - Bone sialoprotein (BSP) is a phosphorylated and sulfated glycoprotein that is a major noncollagenous protein of bone and other mineralizing connective tissues. BSP is characterized by the presence of several polyglutamic acid segments and an RGD motif that mediates cell attachment through a vitronectin-like receptor. Although the precise function of BSP is unknown, the expression of BSP in conjunction with bone formation in vitro indicates a role for this protein in the biomineralization of connective tissues. In this study we used Northern hybridization and in situ hybridization to determine the tissue-specific and developmental expression of BSP during embryogenesis and growth of rat tissues. Analysis of tissues obtained from 13, 17, and 21 day fetuses, and from 4-, 14-, and 100-day-old animals indicates that BSP mRNA expression is restricted to cells actively forming the mineralizing tissues of bone, dentin and cementum. BSP mRNA transcripts were first evident in fully differentiated osteoblasts of 17 day fetal tissues at sites of de novo intramembranous and endochondral bone formation, with maximal expression observed at 21 days of gestation. Thereafter, BSP mRNA levels decreased markedly, and in adult bone hybridization was detected only in the primary spongiosa of long bones. In comparison, mRNAs for osteopontin (OPN), alkaline phosphatase (ALP), and osteocalcin (OC) peaked at 4-14 days postpartum before declining. In the tibiae, Northern hybridization revealed a second peak of mRNA for BSP, ALP, and OPN at 14 days, reflecting an increased osteogenic activity due to the formation of the secondary centers of ossification in the epiphyseal cartilage. In situ hybridization also revealed BSP mRNA in hypertrophic chondrocytes at sites of bone formation, in odontoblasts of the incisor during dentinogenesis, and in cementoblasts during cementogenesis. In view of the restricted distribution and temporal changes in the expression of BSP mRNA that we observed together with the chemical properties of BSP, we believe that this protein has a specific role in mediating the initial stages of connective tissue mineralization. PMID- 1442214 TI - Histomorphometric analysis of resorption and formation in osteoporotics and controls with a mean age of 61 years. PMID- 1442215 TI - Brainstem auditory evoked potentials in patients with mitochondrial encephalomyopathy. AB - Brainstem auditory evoked potentials (BAEPs) were evaluated in three patients with mitochondrial encephalomyopathy belonging to the same family. This study showed marked alterations of BAEPs in all patients: reduction of wave amplitude, poor repeatability of responses in test-retest and abnormalities in wave form and latency. The neuroradiological examinations (CT-scan, MRI) did not show significant structural brain abnormalities. Abnormal BAEPs in our patients may be related to central metabolic disorder rather than hearing loss. PMID- 1442216 TI - Study of the P300 event-related potential through brain mapping in phonological dyslexics. AB - The auditory P300 was studied through brain mapping in 10 phonological dyslexics (7 M and 3 F), who were found to differ significantly from normals in presenting a longer P300 latency and smaller amplitude on the N2-P3 wave. Interesting too was the asymmetry of the P300 distribution between the two hemispheres, with less amplitude on the right. These findings confirm the hypothesis of reduced right hemisphere functioning during the process of information analysis in phonological dyslexics. PMID- 1442217 TI - Indication, efficiency and complications of intrathecal pump supported baclofen treatment in spinal spasticity. AB - In 19 patients, who suffered from severe spinal spasticity of different etiologies and did not respond sufficiently to oral antispastic therapy, intrathecal Baclofen test boli were administered. In 11 patients a DAD (Drug Administration Device) [SynchroMedR Model 8611 H, Medtronic Inc. Minneapolis, USA] was implanted. Catheter dislocation or torsion was the most common complication to be observed in these 11 patients. Long term intrathecal Baclofen application was effective in all patients, as reducing spasticity, flexor spasms and spasm induced pain. In some cases the motor performance ameliorated. PMID- 1442218 TI - Long-term intrathecal baclofen treatment in supraspinal spasticity. AB - Baclofen, a derivate of gamma-amino butyric acid (GABA), is known to be a useful drug in spasticity treatment. To achieve a good therapeutic response higher oral dosages have to be administered related with central side effects. Intrathecal application of Baclofen in microgram range dosages is proved to be effective in spinal spasticity. The efficiency of intrathecal Baclofen in patients suffering from supraspinal spasticity is discussed controversially. We report on 9 patients with long-term intrathecal Baclofen treatment, all of them responding well presenting a marked reduced muscle tone. In most cases an improvement of motor performance and in two cases improved bladder function was observed. The therapeutical dosages administered to patients with supraspinal spasticity exceed those administered to patients with spinal spasticity by approximately 100% without provoking central side effects. Despite the risks connected with this method it has to be considered as treatment of choice in cases of severe supraspinal spasticity. PMID- 1442219 TI - "Premorbid" personality of patients with Parkinson's disease. AB - To elucidate the possible existence of a so called "premorbid parkinsonian personality" we studied 33 patients with Parkinson's disease (PD) and 66 controls who did not differ in age, sex, geographic origin, and cultural level, with the Spanish version of the Minnesota Multiphasic Personality Inventory (MMPI). Females of the PD group obtained significantly higher scores than females of the control group for the scales of hypochondria (p less than 0.01), depression (p less than 0.01), hysteria (p less than 0.05), and social introversion (p less than 0.01). The scores of the males with PD in all of the clinical scales of MMPI did not differ significantly from those of the male controls. These results, despite the difficulty of interpretation of a test done in a retrospective way, would agree with the hypothesis previously suggested of the possible existence of a "premorbid" parkinsonian personality, at least in females. PMID- 1442220 TI - Amoebae free-living. Report of the first Italian case of myelitis. AB - The AA. refer on the first Italian case of amoebae "Limax" primitive myelitis in a 25-year-old man. Microscopical observation showed amoebae free-living, but their cultivation and identification were not possible. The patient recovered because of the propriety of diagnosis and therapy with amphotericin B. PMID- 1442221 TI - Dementia of Alzheimer type (DAT) in a man chronically exposed to pesticides. AB - A patient chronically exposed to pesticides with dementia of Alzheimer type (DAT) is presented. We evaluate the pathogenic role of these substances in the disease and suggest the usefulness of an epidemiological attention on the environmental factors in certain neurodegenerative diseases. PMID- 1442222 TI - [Urologic laparoscopic surgery]. PMID- 1442223 TI - [Therapeutic options in metastatic renal carcinoma]. AB - Within the scope of urogenital tract tumoral diseases, renal adenocarcinoma is the third most frequent neoplasia diagnosed in the adult population. The limited clinical presentations in early analysis and their anarchical behaviour are the cause for 50% to 60% of patients having already developed distant disease at the time of diagnosis. The only curative procedure so far is radical surgery, which is possible when there is a single metastatic site and sometimes even, depending on various factors which will be analyzed, several sites. In these occasions, the traditional therapeutic choices (Hormonotherapy, Chemotherapy, Radiotherapy) have proven to have limited or no efficacy in managing the disease. This fact, together with the successful results obtained in other tumoral processes, have allowed the clinical development of different modalities of Immunotherapy for the management of metastatic renal carcinoma, with results clearly hopeful. This work is a review of the results reported for each of the mentioned therapeutic choices, basically analyzing the role currently played by surgery and immunotherapy in the management of advanced renal carcinoma. PMID- 1442224 TI - [Laparoscopic nephrectomy: a case report]. AB - Presentation and clinical picture outline of a patient who underwent transperitoneal laparoscopy-assisted nephrectomy. The procedure lasted 4 hours and the patient was discharged 72 hours later without incidence or complications. The paper describes the technique (presently unique and for selective indications), as well as the resources that the extensive laparoscopic experience of our group put into practice to perform the first successful laparoscopic nephrectomy in humans in our country. PMID- 1442225 TI - [Current validity of urethroplasty in two stages]. AB - Review of 18 patients with complex urethral stenosis, who underwent a two-stage urethroplasty in our Unit over the last three years. Clinical results have been favourable in all patients and, from the radiological point of view, there has been only one re-stenosis. Complications rate has been low and can be superimposed to that of any urethroplasty procedure. The paper emphasizes the enormous relevance of the care taken between both surgical stages on the procedure's final result. PMID- 1442226 TI - [Ultrasonic retrograde urethrography. Technique. Comparison with radiologic retrograde urethrography]. AB - Using ultrasound scan urethrography (U.S.U.) and radiological retrograde urethrography (R.U.), the anterior urethra has been studied in 61 males in an attempt to establish the best technique to perform U.S.U. and to compare it, from the technical point of view, with R.U. U.S.U. should be made retrogradely filling the urethra with a saline solution, under direct ultrasound guidance, which allows to see the anterior urethra, from the syringe come introduced into the glandular urethra up to the urogenital diaphragm and the beginning of the membranous urethra. Overall, U.S.U. is faster to perform than R.U., nine times cheaper, more comfortable for the patient, and there is no risk of exposure to irradiation or radiological markers. PMID- 1442227 TI - [Endourologic treatment of calyceal diverticulum complicated with lithiasis]. AB - Presentation of 9 cases of calyceal diverticulum symptomatic lithiasis, 6 of which have been treated up to the present time. Of the remaining 3, one patients, in spite of its evolutive character (increased cavity) and moderate pain, prefers to abstain from therapeutic therapy, but undergoes follow-up controls every 6 months; the other 2 cases are waiting endourological treatment. Out of 6 patients who underwent surgery, two cases, who had previously experienced shockwave extracorporeal lithotripsy (SWEL), were advised to have endourological procedures due to persistence of pain and gallstones debris. PMID- 1442228 TI - [Renal carcinoma and non-Hodgkin's lymphoma. A clinical report]. AB - Presentation of one case of a 61-year old male with a non-Hodgkin lymphoma, where a renal cell adenocarcinoma was unexpectedly discovered during and extension study. Review of the pathogenic significance of such association in the light of the various explicative hypothesis of this concurrence. PMID- 1442229 TI - [Renal adenocarcinomas associated with other malignant neoplasms]. AB - The renal adenocarcinoma is not a frequent tumour within the scope of multiple neoplasias, at least in the clinical series. Conversely, it appears at a higher relative rate in the post-mortem series. This paper submits a review of renal adenocarcinoma associated in life to other malignant neoplasias, enumerating their major clinical and epidemiological data. Also, it reviews the literature with regard to frequency and etiology, applying the data to our series. The paper concludes that hypernephroma is not a tumour frequently associated with others in life, given its tendency to be secondary to other primary ones, therefore its development depending on survival to the initial tumour. It also emphasizes the need for adequate anamnesis aimed to detect multi-cancer syndromes and the etiology of multiple neoplasias. Further studies are needed to understand the scope of multiple neoplasias and their relative risk. PMID- 1442230 TI - [Acquired cystic renal disease associated with renal carcinoma: report of 3 cases]. AB - Presentation of three cases of haemodialysis patients with acquired cystic renal disease (ACRD) who, over the course of their illness, developed clear cells renal carcinoma. The paper emphasizes the common association of these two entities and the need to consider ACRD cases as patients at high risk of developing renal neoplasia. PMID- 1442231 TI - [Dermatomyositis as paraneoplastic syndrome of bladder tumor]. AB - The dermatomyositis is a connective tissue disease characterized by changes affecting both the skin and the muscle, appearing most frequently around the fifth and sixth decades and which association to a vesical tumour is very rare. This paper contributes one case of paraneoplastic dermatomyositis associated to infiltrant vesical tumour, presenting erythematous damage in face, nape of the neck and upper thorax, as well as periorbital heliotrope erythema and fingernails base and sides telangiectasia, all of which are typical signs of dermatomyositis. PMID- 1442232 TI - [Bladder amyloidosis]. AB - We present a case of Vesical Amyloidosis (V.A.) in a woman with Rheumatoid Arthritis. Clinical data, other locations and Histochemical findings are consistent with Secondary Amyloidosis. After T.U.R., she was treated with Dimethylsulfoxide (DMSO) and Colchicine. Her severe hematuria disappeared. PMID- 1442233 TI - [Emphysematous cystitis caused by Klebsiella pneumoniae]. AB - Emphysematous cystitis is a very uncommon clinical activity as compared to the high incidence of urinary infections in diabetic patients. The paper explains the pathophysiological mechanisms and updates its clinical and therapeutic diagnostic choices regarding one case of favourable evolution following medical treatment. PMID- 1442234 TI - [Laparoscopic cystoprostatovesiculectomy and ureterosigmoidostomy. Experimental surgical model]. AB - The authors have performed 26 experimental laparoscopic cystoprostatovesiculectomies in pigs, 17 of which were followed by ureterosigmoidostomies, also laparoscopically. Using a 10 mm trocar at the umbilical level (optics), another 10 mm at the hypogastric level (pliers and titanium staple applicator), a third 5 mm in left iliac fossa (pliers) and another 5 mm in right iliac fossa (electric shears), cystectomy is performed with a routine technique: stapling and section of deferents, umbilical arteries, vesical lateral pedicles and prostate-seminal pedicles. A double ligature precedes the section of the urethra in the pelvian fundus. A plier passed within an Amplatz jacket (previously introduced through the anus) assists the laparoscopic ureterosigmoidostomy "in elephant trunk" which is performed by sero muscle suture using 3-zero reabsorbable single-strand material. Overcoming the anatomical differences existing with humans, the illustrated experimental model confirms the possibility of performing this type of procedures in human beings, which would considerably curtail the morbidity associated with this type of surgery. PMID- 1442235 TI - Personality traits and behaviors of alcohol-impaired drivers: a comparison of first and multiple offenders. AB - Using an interview and questionnaire format, 358 driving under the influence of alcohol (DUI) first offenders and 141 DUI multiple offenders were compared on measures of personality traits, drinking behavior and problems, and driving behavior and history. In addition, official driving records for the two groups were compared. Results indicated that multiple offenders were significantly higher in hostility, sensation seeking, psychopathic deviance, mania, and depression than first offenders. Multiple offenders were significantly lower in emotional adjustment and assertiveness. Multiple offenders had significantly more nontraffic arrests, accidents, and traffic tickets than first offenders. They also consumed significantly more alcohol, evidenced more alcohol problems, and had higher BACs at the time of arrest than first offenders. Results are discussed in terms of general problem behavior and implications for intervention and treatment. PMID- 1442236 TI - Readiness for smoking change among middle-aged Finnish men. AB - According to the transtheoretical model of change, smoking cessation attempts are preceded by three stages: precontemplation, contemplation, and preparation. These stages have shown great utility in predicting and impacting on behavior change. This cross-cultural study examined the distribution of the stages within a 33% random sample of middle-aged Finnish men. Of 490 regular smokers, 57.6% were in precontemplation, 29.4% in contemplation, and 13.0% in preparation. Five conceptual clusters were used to predict the stage membership. The number of lifetime quit attempts and the number of 24-h quit attempts in the past 12 months were found to be the best discriminators among the stages. The overall correct classification rate into stages using stepwise discriminant function analysis was 64.0%, substantially better than the chance rate. However, the analysis was successful for precontemplators only. Results showed that most smokers were precontemplators. Previous attempts to reduce smoking provided some predictive information concerning stage membership. Demographics, addiction to smoking, current smoking, smoking environment, and quit history were incomplete predictors of stage membership, as theoretically predicted. PMID- 1442237 TI - Personal and parental alcohol abuse, and victimization in obese binge eaters and nonbingeing obese. AB - Current obesity research has begun to emphasize the importance of pretreatment assessment and more individually tailored treatment protocols. Obese binge eaters have been identified as a subgroup of the obese who do not respond well to standard behavioral treatment programs. We were interested in identifying variables that are important to consider when assessing and treating obese binge eaters. The present study assessed the prevalence of personal alcohol abuse, parental alcohol abuse, and victimization in 62 males and 274 females seeking treatment for obesity. Obese binge eaters (OBE) had significantly greater rates of personal alcohol abuse, parental alcohol abuse, and victimization than the nonbingeing obese (NBO) in our sample. Further studies of the OBE population are recommended. PMID- 1442238 TI - The effects of caffeine and nicotine consumption on mood and somatic variables in a penitentiary inmate population. AB - A sample of 144 inmates from a maximum security penitentiary responded to a request for information regarding their average daily intake of nicotine and caffeine. They also rated the quality of their appetite and sleep, their level of concentration, their mood and specific feelings of anger, anxiety, frustration, and irritability. Factor analysis generated a two-factor solution of these variables, namely general mood state (mood, anxiety, anger, frustration, and irritability) and a somatic state (appetite, concentration, and sleep). Analysis of variance showed an interaction between level of smoking (nonsmokers, low and high cigarette smokers) and caffeine use (moderate vs. high) on the general mood factor. Nonsmokers who consumed high levels of caffeine experienced poorer general mood than any other group. There was a main effect of cigarette smoking status on the somatic factor, such that greater dissatisfaction was associated with greater consumption. Caffeine consumption was generally high, averaging 800 mg of caffeine per day, per inmate, well above the amount considered to be potentially damaging to health. PMID- 1442239 TI - The interaction of sociological and biological factors in adolescent cigarette smoking. AB - This article considers the interaction of social and biological factors in the context of adolescent cigarette smoking. Parent and peer smoking are the sociological variables and testosterone is the biological indicator. The subjects are 212 males and females 12-14 years of age. The findings support the interaction model, suggesting that both sociological and biological factors are necessary for understanding adolescent smoking. PMID- 1442240 TI - Long-term maintenance following attainment of goal weight: a preliminary investigation. AB - The present study sought to determine whether the high relapse rates observed among subjects in fixed length behavioral-based weight loss programs would be lowered if subjects were allowed to continue in treatment until they had reached their desired weights. Five hundred seventeen (517) clients at a commercial weight-loss program were surveyed approximately 1 year posttreatment regarding their current weight status. Of the 267 subjects who responded to the mailed survey, it was found that 82% remained within 10% of their posttreatment weights at the time of the follow-up. Of particular interest was the fact that weight trends during the intervening year suggested subjects were actively and effectively calibrating their weight. It was concluded that the high relapse rates typical for this mode of treatment may be an artifact of premature treatment cessation and further investigation is indeed merited. PMID- 1442241 TI - Developmental level as a predictor of alcoholism treatment response: an attempted replication. AB - Over 12 years ago, a developmental level (DL) cognitive measure derived from the Rorschach was found to be a powerful predictor of alcohol-related outcomes following behaviorally oriented inpatient alcoholism treatment. These findings represent the strongest evidence of a relationship between cognitive functioning and treatment response. The current pilot study attempted to determine whether the large effects previously obtained with the DL measure could be replicated. The Rorschach was administered during the first week of treatment to 20 male alcoholic patients attending 1-month day hospital rehabilitation program. The Addiction Severity Index (ASI) was administered upon entry into treatment and a follow-up ASI was also administered 7 months after treatment entry. A higher DL was found to be significantly related to less recent drinking and intoxication at baseline as well as to lower alcohol-related problem levels in general. However, all of the relationships between DL and alcohol-related behaviors at follow-up were found to be either small or in a direction opposite to that hypothesized. Some of the reasons for the discrepancy between the findings of the current study and the earlier study are discussed. PMID- 1442242 TI - Alcohol abusers' perceptions of the accuracy of their self-reports of drinking: implications for treatment. AB - Several major literature reviews have concluded that alcohol abusers generally give valid self-reports when interviewed under certain conditions. Nevertheless, across all studies a small proportion of alcohol abusers' self-reports continue to be suspect. Sources of invalidity may relate to subject factors or to circumstances under which data are collected. One novel way of gaining information about conditions possibly affecting the accuracy of alcohol abusers' self-reports is to ask the subjects themselves. In the present study, 208 alcohol abusers were asked about (a) how accurately different people they knew or lived with would report their (i.e., the subjects') drinking at different levels (e.g., abstinent, 1-4 drinks) compared to the subjects' own reports; (b) how accurate their own reports would be at different levels of ethanol consumption; and (c) how accurate their own reports would be when interviewed under different conditions (e.g., by phone, their therapist, a researcher, their employer). The results are largely consistent with studies that have empirically examined the validity of alcohol abusers' self-reports. Suggestions for future research and evaluation are offered. PMID- 1442243 TI - Compliance of genetic code with base-composition deflecting pressure. AB - Gene DNAs of different organisms show a wide variation in their G+C content as much as 20% to 80%. This variation has been regarded as the result of the compliance of the genetic code with the base-composition-deflecting mutational pressure. To make possible a quantitative discussion of this genetic code's elasticity, we made a statistical study of the G+C frequency at the 1st, 2nd, and 3rd positions of codons: 4.5 x 10(6) codons in 11,981 protein coding regions in the DNA data base were analyzed. The data were examined quantitatively by using a species-independent universal equation which describes the base frequencies at the three codon sites in terms of the constraint parameters characteristic of the sites and an intersite interaction. By a best fitting procedure between theoretical curves and data points, the constraint parameters and the characteristic G+C contents to which the 1st and the 2nd site base compositions are bound were determined. The base substituting mutation of the coding sequence under the base-composition-deflecting pressure is divided into following three stages of the different compliance from the elastic one to the rigid: 1) the 3rd position of codons change by synonymous substitution; 2) the 1st and then 2nd positions change accompanying amino acid replacement; and 3) in the organisms exposed under an extremely high base composition deflecting pressure, the codon table is forced to be altered. The compliance parameters were derived quantitatively for the first two stages. In conclusion, a simultaneous analysis of data from organisms as divers as virus and man discovered that there is a set of constraints common to species, which governs the frequency of codon bases, and it can be described by a universal equation. PMID- 1442244 TI - Selenium and arsenic in biology: their chemical forms and biological functions. AB - Based on the recent development of analytical methods, sensitive systems for the analysis and speciation of selenium and arsenic have been established. A palladium addition technique was developed for the accurate determination of selenium in biological samples using graphite furnace atomic absorption analysis. For the speciation of the elements, combined methods of HPLC either with ICP-AES or with ICP-MS were found to work well. These systems were applied to the elucidation of the chemical form of the elements in natural samples. Some chemical properties of the selenium-mercury complex in dolphin liver were elucidated: i.e., it was a cationic, water-soluble, low molecular weight compound containing selenium and mercury in a 1:1 molar ratio, and was shown to be different from a known selenium-mercury complex, bis(methylmercuric)selenide. The major selenium compound excreted in human urine was revealed to be other than any of those previously identified (TMSe, selenate, and selenite). TMSe, a suspected major metabolite in urine, was found, if at all, in low levels. The major water soluble, and lipid-soluble arsenic compounds in a brown seaweed, U. pinnatifida (WAKAME), were rigorously identified, and the results were compared with other data on marine algae and animals. The major organic arsenic compounds (termed "arseno-sugars") in marine algae commonly contain 5-deoxy-5-dimethylarsinyl ribofuranoside moiety. There are various kinds of arseno-sugar derivatives containing different side-chains attached to the anomeric position of the sugar, and the distribution of each arsenic species seems to be related to algal species. The arseno-sugar (A-XI) is present in every alga so far examined, is metabolized to lipids, and possibly may play some specific role in the algal cells. On the other hand, the major arsenic compound in fish, crustacea and molluscs has been identified as arsenobetaine, which is an arseno-analog of glycinebetaine, a very common osmo-regulator in living organisms. Arsenobetaine is not detected in marine algae while arseno-sugars are not present in marine animals except for some molluscs which contain both compounds in considerable amounts. Arsenobetaine is present in the urine of human beings who have eaten foods derived from marine animals. PMID- 1442246 TI - Oral contraception noncompliance: the extent of the problem. AB - Compliance has been defined as the extent to which a patient's behavior coincides with the clinical prescription. The lowest expected failure rate of oral contraceptive (OC) use has been suggested to be 0.1%; however, in typical users, the failure rate varies by age, race, and marital status. In some populations in the United States (eg, unmarried black adolescents), the failure rate is 18%; rates that factor in the occurrence of abortions suggest an overall failure rate of 6.2% during the first year of use. If the annual failure rate of 6.2% is assumed, long-term failure rates rapidly approach 25% to 50% (ie, the proportion of users who will experience an unintended pregnancy) over 10 years of use. The gap between the lowest expected failure rate and the failure rates seen in typical users is related in large part to problems of compliance. Compliance with OC use includes both correct daily use and continuing use. Factors that contribute to OC discontinuation include the experience of side effects, fears and misinformation about OC side effects fueled by negative media reports, and intermittent use. There are relatively few data regarding the issue of missed pills and correct use, but studies suggest that adolescents may miss an average of 3 pills a month, and at least 20% to 30% of individuals miss a pill every month. Patients may have difficulty in the transition from one packet of pills to the next, and missed pills that extend the hormone-free interval may contribute to the failure rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442245 TI - Mechanisms for gene conversion and homologous recombination: the double-strand break repair model and the successive half crossing-over model. AB - Two mechanisms for gene conversion and homologous recombination were discussed. (1) The double-strand break repair model. A double-strand break is expanded to a gap, which is then repaired by copying a homologous sequence. The gene conversion is often accompanied by crossing-over of the flanking sequences. We obtained evidence for this model in Red pathway of bacteriophage lambda and RecE pathway of E. coli. (2) The successive half crossing-over model. Half crossing-over leaves one recombinant duplex and one or two end(s) out of two parental duplexes. The resulting ends are, in turn, recombinogenic. Successive rounds of the half crossing-over mechanism explains why apparent plasmid gene conversion in RecF pathway of E. coli is not accompanied by crossing-over. This model can explain chromosomal gene conversion if we assume that the donor is first replicated. Gene conversion during mating-type switching in yeast, antigenic variation in unicellular microorganisms, and chromosomal gene conversion in mammalian somatic cells are explained by this model. Distinguishing between these two mechanisms is important in understanding recombination in yeast and mammalian cells and also in its application to gene targeting. PMID- 1442247 TI - Medical aspects of oral contraceptive discontinuation. AB - Oral contraceptive (OC) compliance is adversely affected by three medical factors: side effects, poor cycle control, and patients' fears of serious diseases. Most physicians recognize these factors but fail to understand their true impact on continuation rates. In one study, half of current OC users who changed brands and half of former OC users cited unwanted side effects as their reason for discontinuation. Moreover, a substantial number of women discontinue OCs without consulting their physicians. Among the so-called nuisance side effects cited by patients, the most prominent are bleeding irregularities. In new patients just beginning OC therapy, bleeding irregularities such as breakthrough bleeding and amenorrhea can lead to a very high discontinuation rate; as many as 50% of new users discontinue OCs before the end of the first year because of such side effects. OC discontinuation rates among other patient populations vary. The problem has not been studied extensively, but existing data show the problem is a large one. One study involving 550 women of various ages and years of OC use confirmed that cycle control problems led many women to discontinue OC use--often resulting in an unplanned pregnancy. Six percent of the women in this study discontinued OC use because of poor cycle control, and 23% of this group experienced subsequent unwanted pregnancies. In contrast, clinical tolerance with the new progestins such as gestodene is good; in one study 86% of patients had normal bleeding patterns. The principal consequences of poor cycle control are loss of confidence in the OC and the physician, increased anxiety, disruption of sexual relations, additional physician calls and visits, pregnancy tests, discontinuation, and noncompliance. The perception that European women have regarding the pill is that it is a reliable method that does not interfere with sexual activities. However, doubts about the safety of OCs influence compliance with the method. While concerns regarding blood clots have diminished, the fear of cancer is still a concern for many women. The androgenic side effects of weight gain, acne,and breast tenderness are particularly troubling for adolescents, who are sensitive to changes in body image. In one recent study, 20% to 25% of women stopped taking OCs because of weight gain or acne, and another 25% stopped because of fear of cancer. The medical component of improving compliance is the physician's choice of OC. Formulations with low, effective doses of hormones and the fewest side effects should be selected. Cycle control and the side-effect profile are improved with the new progestins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1442248 TI - Oral contraceptives and cycle control: a critical review of the literature. AB - Control of spotting and breakthrough bleeding and absence of withdrawal bleeding, collectively termed cycle control, is the single most important determinant of whether a new user of oral contraceptives (OCs) will continue this method. However, information about different OC preparations and how they affect such problems, including the effects of progestogen and estrogen phasing and the components of these hormones, is scant and confusing. Studies cited in this report reveal highly variable rates of bleeding problems in women taking OCs: after 6 months of OC use, the prevalence of spotting varied between 0% and 8.5%; of breakthrough bleeding, 0% and 12.2%; and of amenorrhea, 0% and 5.8%. At least some of this variation is attributable to differing study populations and cultures, study designs, and the manner in which data were collected and reported. However, methodologic weaknesses were common, often involving lack of randomization and blinding, and attrition rates were high. Despite these limitations, it is clear that the frequency of bleeding problems decreases with continuing use of OCs, emphasizing the need for patient reassurance about the transient nature of these problems. In addition, gestodene-containing preparations appear to offer better cycle control than do desogestrel-containing preparations and levonorgestrel-containing preparations better control than norethindrone-containing preparations. However, the strongest lesson to emerge is the need for more rigorous studies to adequately address questions of comparative bleeding problems, particularly with newer triphasic formulations. These conclusions underscore the importance of counseling new OC users about the possibility of bleeding problems, reassuring them that most such problems are temporary, and, that if compliance is maintained, these will not impair contraceptive efficacy. PMID- 1442249 TI - Cultural factors in oral contraceptive compliance. PMID- 1442250 TI - Noncontraceptive benefits of modern low-dose oral contraceptives. AB - Most oral contraceptive formulations in current use contain 50 micrograms or less of ethinyl estradiol and 1 mg or less of the various progestins: norethindrone (0.5-1 mg), norgestrel (0.3-0.5 mg), or levonorgestrel (0.05-0.25 mg) [1]. The new generation of progestins--norgestimate, desogestrel and gestodene--are derived from levonorgestrel, the biologically active enantiomer of norgestrel. These steroids have specific metabolic and pharmacologic activity that allow oral contraception at lower doses than previous progestins. Desogestrel and norgestimate are both prodrugs and must undergo hepatic and gastrointestinal metabolism to become biologically active compounds. Gestodene is immediately and completely bioavailable [2]. For the new formulations containing less than 50 micrograms of ethinyl estradiol, the incidence of complications has decreased. With most of the early medical problems identified, current research can now focus on other aspects of oral contraception such as compliance and OC use failure. Prominent noncontraceptive health benefits have been observed in OC users and represent new directions for future research. When the risk-benefit ratio of OC use is evaluated in healthy women today, it clearly favors the benefits. However, these will not be fully realized without an increase in method compliance. PMID- 1442251 TI - Patient education and understanding: a critical review. AB - In the United Kingdom, family planning services are readily available to all women, regardless of economic status. Oral contraceptives play an important role in this effort, yet studies suggest that many patients still do not understand how to use these agents appropriately. Specifically, poor patient compliance is much more prevalent than initially thought. Factors influencing compliance in UK populations include age, socioeconomic group, education, side effects, packaging, and health care delivery. In order for these medications to be effective among various female populations, there is a need for greater emphasis on patient education about oral contraception. Several possible approaches are discussed. PMID- 1442252 TI - Patient counseling. AB - The success or failure of oral contraceptive (OC) use depends very heavily on the type and extent of the counseling a woman is given both before and during pill administration. If she selects the OC as her method of choice after considering all the options, a clear, detailed, and accurate discussion should ensue about its proper use; any fears that she may have should be explored; and great emphasis should be placed on the advantages and effectiveness of our current pills and, above all, on their numerous health benefits. All her questions should be answered in a thorough and emphatic fashion, and she should be encouraged to ask for additional answers at any time in the future. Finally, if her history reveals that she is at risk for sexually transmitted diseases (STDs), she must be informed that the pill, while highly protective against unplanned pregnancy, will not provide protection against most STDs or HIV infections, and that she should also use condoms and/or a female barrier contraceptive with each act of intercourse. PMID- 1442254 TI - Heparin and Related Polysaccharides. Proceedings of an international meeting. Uppsala, Sweden, September 1-6, 1991. PMID- 1442253 TI - Heparin--an introduction. PMID- 1442255 TI - Two enzymes in one: N-deacetylation and N-sulfation in heparin biosynthesis are catalyzed by the same protein. PMID- 1442256 TI - Metabolism of plasma membrane-associated heparan sulfate proteoglycans. PMID- 1442257 TI - Lysosomal degradation of heparin and heparan sulphate. PMID- 1442258 TI - Heparin protein interactions. PMID- 1442259 TI - Role of protein conformational changes, surface approximation and protein cofactors in heparin-accelerated antithrombin-proteinase reactions. PMID- 1442260 TI - The interaction of glycosaminoglycans with heparin cofactor II: structure and activity of a high-affinity dermatan sulfate hexasaccharide. AB - The binding sites for dermatan sulfate and heparin in HCII overlap but are not identical. This may explain the observation that HCII binds non-specifically to heparin oligosaccharides but preferentially binds to a minor hexasaccharide isolated from dermatan sulfate having the structure shown in Fig. 4B. The tissue distribution of dermatan sulfate molecules containing the high-affinity HCII binding site may regulate HCII activity in vivo. Finally, in the presence of dermatan sulfate or heparin, the N-terminal acidic domain of HCII may interact with the hirudin-binding site of thrombin to produce maximal stimulation of the thrombin-HCII reaction. PMID- 1442261 TI - The interaction between LACI and heparin. PMID- 1442262 TI - Tissue factor pathway inhibitor and heparin. PMID- 1442263 TI - Chemical synthesis and hemisynthesis in the field of glycosaminoglycans. PMID- 1442264 TI - Heparin in the prevention and treatment of arterial thromboembolism. PMID- 1442265 TI - Relationship between dose, anticoagulant effect and the clinical efficacy and safety of heparin. PMID- 1442266 TI - Regulation of protease nexin-1 activity by heparin and heparan sulfate. PMID- 1442267 TI - New approaches for defining sequence specific synthesis of heparan sulfate chains. AB - Mammalian cells synthesize heparan sulfate proteoglycans (HSPG) which consist of core proteins with covalently linked glycosaminoglycans (GAGs) of 50-150 disaccharide units. The GAGs exhibit great structural diversity which arise from differing arrangements of alternate disaccharide units. It has been hypothesized that HSPG may be involved in regulating the most basic aspects of cell biologic systems such as adhesion, proliferation and differentiation. However, considerable doubt exists about the specific nature of the above interactions because of a failure to isolate GAGs of unique monosaccharide sequence with appropriate biologic activities. We have demonstrated that mouse LTA cells synthesize cell surface heparan sulfate proteoglycans with regions of defined monosaccharide sequence that specifically interact with antithrombin (HSPGact). However, it remains unclear how HSPGact can be generated by a biosynthetic pathway with no simple template for directing the ordered assembly of monosaccharide units. To examine this issue, we treated LTA cells with ethylmethane sulfonate and then identified mutants that exhibit decreased antithrombin binding to heparan sulfate chains but possess no gross defects in glycosaminoglycan biosynthesis. After screening 40,000 colonies, we isolated 7 stable mutants which synthesize 8-27% of the wild type HSPGact but produce normal amounts of other HSPG. These mutants are recessive in nature, and fall into at least two different complementation groups. The delineation of the molecular basis of these defects should greatly improve our understanding of how cells synthesize HSPG with regions of defined monosaccharide sequence. PMID- 1442268 TI - Anti-inflammatory effects of heparin and its derivatives: inhibition of complement and of lymphocyte migration. PMID- 1442269 TI - Heparan sulphate proteoglycans: molecular organisation of membrane--associated species and an approach to polysaccharide sequence analysis. PMID- 1442270 TI - Regulation of the gene that encodes the peptide core of heparin proteoglycan and other proteoglycans that are stored in the secretory granules of hematopoietic cells. PMID- 1442271 TI - Structural and functional diversity of the heparan sulfate proteoglycans. PMID- 1442272 TI - Heparan sulfate proteoglycans and signalling in cell adhesion. PMID- 1442273 TI - Animal cell mutants defective in heparan sulfate polymerization. PMID- 1442274 TI - Study design for the prevention of aerodigestive tract cancers. PMID- 1442275 TI - Participant enrollment, participation, and compliance in chemoprevention trials. AB - Chemoprevention trials offer exciting opportunities for decreasing the risk for cancer. Close attention to the recruitment, enrollment, and compliance of participants will aid greatly in both the cooperation of participants and the long-term adherence that are essential for the success of these trials. PMID- 1442276 TI - A population-based trial of beta-carotene chemoprevention of head and neck cancer. PMID- 1442277 TI - Chemoprevention of Barrett's esophagus and oral leukoplakia. PMID- 1442278 TI - Carotene and retinol efficacy trial: lung cancer chemoprevention trial in heavy cigarette smokers and asbestos-exposed workers. CARET Coinvestigators and Staff. PMID- 1442279 TI - An intervention trial in high-risk asbestos-exposed persons. PMID- 1442280 TI - Chemoprevention of aerodigestive epithelial cancers. PMID- 1442281 TI - Epidemiology of vitamin A and aerodigestive cancer. PMID- 1442282 TI - Multiple primary squamous carcinomas of the upper aerodigestive tract. PMID- 1442283 TI - Smokeless tobacco and aerodigestive tract cancers: recent research directions. PMID- 1442284 TI - Hamster lung cancer model of carcinogenesis and chemoprevention. PMID- 1442285 TI - Culture conditions affect expression of the alpha 6 beta 4 integrin associated with aggressive behavior in head and neck cancer. PMID- 1442286 TI - Growth factors and other targets for rational application as intervention agents. PMID- 1442287 TI - Micronuclei as intermediate end points in intervention. PMID- 1442288 TI - Exercise, calories, and fat: future challenges. PMID- 1442289 TI - A model system for studying nutritional interventions on colon tumor growth: effects of marine oil. AB - Lipid nutrition effects were evaluated on the growth of a transplantable colon tumor (CT-26) at various sites in the BALB/c mouse. CT-26 implanted into the back or flank of these mice grew well independent of the quality or quantity of fat in the diet. However, when implanted in the mid-portion of the descending colon, tumor growth was related to the level of dietary saturated (coconut oil) or n-6 unsaturated (safflower oil) fat in the diet. Similar findings were obtained when the tumor was utilized in a pulmonary colonization assay. Dietary marine oil (mainly EPA, and DHA n-3 polyunsaturated oils) was found to markedly impair the growth of CT-26 implanted in the bowel and lung, but not in the back. Thus, CT-26 exhibits nutrition responsiveness at certain sites, but not at others. This may help to explain contradictory findings concerning dietary lipids in certain studies. Inhibition of tumor growth by marine oils may afford preventive or chemotherapeutic implications as its mode of action unfolds. Histologic findings in bowel tumors from mice fed marine oil but not other oils revealed focal areas of necrosis. It is appreciated that arachidonate metabolism is competitively interfered with by EPA in both cyclooxygenase and lipoxygenase pathways. The possibility is raised that the metabolism of marine oils in this model system may generate lipid peroxidation products to a greater extent than n-6 lipids and in turn is associated with focal areas of necrosis. A model system of nutritionally non-responsive and nutritionally responsive sites for the post-promotional growth of a bowel tumor affords the opportunity to explore lipid effects with control and test tumors in hosts fed identical lipid nutriture. PMID- 1442290 TI - Enhancement of pancreatic carcinogenesis by dehydroepiandrosterone. PMID- 1442291 TI - Caloric restriction and experimental carcinogenesis. PMID- 1442292 TI - Breast cancer--the optimal diet. AB - In summary, the evidence based upon global and metabolic epidemiology, and animal studies supported by biologic understanding of the various mechanisms in which dietary fat can affect promotion and progression of breast cancer supports the concept that dietary fat, in particular, certain types of fat, and dietary fiber affect the causation, promotion, and progression of breast cancer. The epidemiologic evidence of the link between breast cancer and dietary fat is still controversial due to methodological problems in designing a valid test. Also a number of studies dealt with the question of fat intake in pre-menopausal women, where admittedly the association is weak. What now needs to be done is to verify the effect of a low-fat diet in post-menopausal breast cancer patients. We suggest that a similar trial on pre-menopausal breast cancer patients in conjunction with ovarian ablation should be conducted. The question to be considered is what in terms of dose, type, and duration of fat and fiber will be required to obtain a measureable effect on the recurrence rate and survival of breast cancer patients. PMID- 1442293 TI - Dietary fat and breast cancer: testing interventions to reduce risks. PMID- 1442294 TI - Effects of voluntary exercise and/or food restriction on pancreatic tumorigenesis in male rats. AB - Studies were undertaken to evaluate the effects of caloric restriction on voluntary exercise in a rat model of pancreatic cancer. Suckling male Lewis rats were initiated with 3 doses (30 mg/kg body weight) of the pancreatic carcinogen azaserine. At 28 days of age they were weaned to one of four experimental protocols; namely, sedentary/ad libitum fed, voluntary exercise/ad libitum fed, sedentary/food restricted, and voluntary exercise/food restricted. Voluntary exercise was provided by free access to running wheels fitted with odometers. Food restriction was intended to be mild, at less than 10% reduction of ad libitum intake. Putative pre-neoplastic pancreatic foci were identified microscopically at 4 months post-azaserine treatment. As previously shown, food restriction led to increased wheel activity, but the increased activity could not be maintained beyond the first half of the post-initiation treatment phase. Additionally, the extensive wheel running occurred only when available food was restricted by greater than 10%. Exercise per se had a lesser effect compared to food restriction on pancreatic tumorigenesis. PMID- 1442295 TI - Possible mechanisms through which dietary lipids, calorie restriction, and exercise modulate breast cancer. PMID- 1442296 TI - Dietary fat, calories, and mammary gland tumorigenesis. AB - In this communication, a vast array of studies designed to examine the relationship between dietary fat and experimental mammary gland tumorigenesis was reviewed and critiqued. It is clear, as reported by many laboratories, that as the fat content of the diet is increased from a low or standard level to a high level, a consistent and substantial increase in the development of rodent mammary gland tumors is observed. The longer the duration the high-fat diet is fed, the greater the enhancing effect on tumorigenesis. Furthermore, the stimulatory effect of a high-fat diet is observed even when fed commencing late in an animal's life. A multitude of studies also have provided evidence that the type of fat can markedly influence the development of rodent mammary gland tumors. In general, high dietary levels of unsaturated fats (e.g., corn oil, sunflower-seed oil) stimulate this tumorigenic process more than high levels of saturated fats (e.g., beef tallow, coconut oil); diets rich in certain fish oils (e.g., Menhaden oil, Max EPA) are often the most inhibitory to this tumorigenic process. Importantly, however, supplementation of saturated fat or fish oil diets with modest amounts of unsaturated fats, e.g., corn oil, often negates the mammary tumor inhibitory activities of these fats. Thus, rather extreme differences in the types of fat are required for a differential in mammary gland tumorigenesis; common proportionate blends of different fats of animal, plant, and/or fish origin are often unable to differentially influence this tumorigenic process. Diets rich in monoenoic fatty acids, e.g., those containing high levels of olive oil, have been examined in a number of studies; results from these studies have been inconsistent. A number of reports suggest that the increase in development of mammary tumors in rodents fed a high-fat diet, compared with those fed a low fat diet, is due to specific metabolic activities of the fat per se, activities independent of a caloric mechanism. Careful analysis of these reports suggest that such a conclusion may not be totally warranted. Indeed, persuasive evidence is accumulating indicating that the major mammary tumor development enhancing activities of a high-fat diet may be via a caloric (energy) mechanism. Caloric restriction, even in animals fed a high-fat diet, significantly suppresses mammary tumor development. Even mild caloric restriction (e.g., 12%) can significantly suppress development of mammary tumors in rodents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1442297 TI - Dietary fat and breast cancer: a search for mechanisms. PMID- 1442298 TI - Selected recent studies of exercise, energy metabolism, body weight, and blood lipids relevant to interpretation and design of studies of exercise and cancer. PMID- 1442299 TI - Former athletes have a lower lifetime occurrence of breast cancer and cancers of the reproductive system. PMID- 1442300 TI - Voluntary exercise and experimental mammary cancer. AB - The results of these studies indicate that voluntary activity suppresses the development of chemically and virally induced primary mammary tumors in rats and mice fed high-fat diets. These diets were chosen to mimic the current U.S. fat consumption of approximately 40% of calories as fat. It remains to be seen if activity exerts a similar suppressive effect on animals fed their customary low fat diet (10% calories as fat). In general, the activity profiles of the female Fischer F-344 and Sprague-Dawley rat and the C3H/o mu j mouse exhibited a similar pattern with an early peak followed by a gradual plateau over time. The effects of activity on body fat composition showed a trend toward a decreased percent of body fat when compared to sedentary animals but a statistically significant decrease was found only in the F-344 female rat. In the DMBA model, carcinogen dose did alter outcome parameters. For example, time to first tumor was extended under low- but not high-DMBA conditions, and, conversely, tumor multiplicity was significantly decreased in the high- but not low-DMBA group. In the NMU model, an inverse association was found between the amount of activity and tumor incidence. A similar association was not found with the DMBA model. The reason for this is uncertain, but further analysis in terms of other parameters such as total tumor number may shed more light on this discrepancy. The suppressive effect of activity on the MMTV-induced mouse mammary tumor is of particular interest since it raises the possibility that activity may exert effects on the process of provirus insertion, and/or oncogene activation--an area of great potential promise in cancer prevention. Activity appeared to enhance the volume and to a lesser degree the number of metastatic foci in the lungs of F-344 retired breeders under high-fat but not medium-fat conditions. In addition, the most active animals in the high-fat group exhibited the greatest volume of metastases. These results, together with those in the NMU model, point to the critical importance of the quantity of voluntary activity an animal engages in and its relation to both primary and secondary cancer prevention. They imply that beyond a certain point of either frequency or intensity, the beneficial effect of exercise may be nullified by competing deleterious effects. The metastases study has also brought to light the importance of dietary fat as a potential intervening variable.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1442301 TI - Effect of amount and type of exercise on experimentally induced breast cancer. AB - It appears that exercise derived by treadmill running can enhance or inhibit the development of mammary cancer depending on the intensity and duration of the activity. The effects of timing of exercise relative to the phases of carcinogenesis and the frequency of exercise on the tumorigenic response in the mammary gland have yet to be studied. What is needed are further investigations of a spectrum of exercise conditions that exert differential effects on measures of physical fitness, energy intake, body composition, and/or the efficiency of utilization of carbohydrate, fat, and protein as energy substrates. This should facilitate identification of critical relationships between physical activity and the risk for cancer. This goal can best be achieved initially through carefully controlled laboratory studies using appropriate experimental systems. There are several mechanisms by which exercise could alter the course of tumor development. A goal in this field should be to first characterize the influence on tumorigenesis of amount and type of exercise that have differential effects on metabolism and thereafter proceed to investigate the basis for the effects observed. Experiments should be designed to dissociate effects of exercise related to local and/or systemic changes induced by skeletal muscle contraction from those attributable to changes in energy expenditure. Ultimately, investigations of the type proposed should allow for determination of whether the quantity and quality of exercise needed to attain health-related benefits for chronic diseases such as cancer differs from what is recommended for fitness benefits. This should also permit formulation of a specific set of recommendations about the amount and type of physical activity that in concert with appropriate dietary practices can significantly reduce the risk for cancer. PMID- 1442302 TI - The influence of physical activity on the incidence of site-specific cancers in college alumni. PMID- 1442303 TI - Modulation of chemical toxicity by modification of caloric intake. AB - Caloric restriction increases maximum achievable lifespan and offsets the time to development of degenerative disease. Part of these desirable effects may result from positive modulation of toxic events. We have shown that when rodents are placed on a diet that is reduced in total calories by 40%, several beneficial changes on biochemical systems which impact on toxicologic processes are positively enhanced. Lipid metabolism is reduced and, therefore, the potential for lipoperoxidation is reduced. Additionally, activity of enzymes that produce free radicals as byproducts (cytochrome P4502C11) are also reduced. Concurrently, we have shown that the "effective" activity of catalase and the activity of superoxide dismutase (which are required for the detoxification of toxic oxygen radicals) are significantly increased by caloric restriction. The activities of enzymes of drug and xenobiotic metabolism are also altered by caloric restriction. The effect upon activity may be to either decrease or increase activity, dependent upon whether the enzyme activates compounds to intermediates which may be more toxic or whether the enzyme acts to reduce toxicity. We have also shown that caloric restriction may affect the initiation stage of carcinogenesis. Aflatoxin B1 binding to hepatic nuclear DNA was reduced by caloric restriction (caloric restriction reduced both major adducts that are formed upon exposure to aflatoxin B1). caloric restriction also reduced cytochrome P4502C11 which converts aflatoxin B1 to its toxic epoxide, and may partly explain the reduction in binding. These results suggest that caloric restriction may, in part, extend the time to development of degenerative disease by altering basic biochemical mechanisms of toxicity. PMID- 1442304 TI - Caloric intake, dietary fat level, and experimental carcinogenesis. PMID- 1442305 TI - Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. PMID- 1442306 TI - Human B lymphocytes: phenotype, proliferation, and differentiation. PMID- 1442307 TI - Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system. PMID- 1442308 TI - Cellular and molecular mechanisms of B lymphocyte tolerance. AB - A paradox of immunology is that the immune system is distributed so widely in the body, as a large number of cells that discharge most of their effector functions as single cells; but, at the same time, the elements of the system are so very interdependent, not only via specialized cell clusters and microenvironments, but also by mobile feedback loops, cellular and molecular. The end result is that one cannot really understand one element of the system without understanding every other, at least to a degree. Certainly, tolerance cannot be isolated from immune activation, nor B cell from T cell tolerance, rendering the task of the reviewer somewhat thankless. This being said, the last few years have seen wonderful progress in our grasp of B cell tolerance, to which the transgenic revolution has contributed a great deal. The fact that B cell tolerance exists as an important component of self-tolerance has been firmly established, as have the limits of the process in terms of both the survival of low-affinity antiself clonotypes and the question of location and concentration of antigen required for tolerance induction. Two processes have been identified as key alternatives: clonal abortion/maturation arrest/deletion and induction of clonal anergy. The latter requires a less strong Ig receptor crosslinking signal, may be partial, and is reversible. Recognition of these facts has prompted both experimentation and speculation on possible functions of the anergic cell. One unsatisfactory area, which we have not addressed because nothing like a consensus has been reached, is T cell-mediated suppression and its possible effects on tolerant states, including anergy induction in B cells. The phenomenology of suppression is too striking to sweep under the carpet, and suppressor T cell memory in particular (Adelstein et al., 1990) requires much more investigation; however, suppression has not been shown to play a major role in any of the best-studied transgenic models. These can readily be explained on the basis of direct interactions between the B cell target for abortion or anergy and the self antigen in question. The biochemical basis of discrimination between immunity and tolerance has also progressed, but not as fast. This is understandable, as so many signaling pathways have to come together for full immune induction, and as immaturity of the signal transduction pathway plays a profound role that must be studied in normal cells, with all the attendant difficulties of cell separation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1442309 TI - Animal models for acquired immunodeficiency syndrome. PMID- 1442310 TI - The vulnerable child: new evidence, new approaches. PMID- 1442311 TI - IgG subclasses. PMID- 1442312 TI - New concepts in otitis media: results of investigations of the Greater Boston Otitis Media Study Group. PMID- 1442313 TI - The evaluation of ear canal, middle ear, temporal bone, and cerebellopontine angle masses in infants, children, and adolescents. AB - Ear canal, middle ear, temporal bone, and CPA angle masses (except for cholesteatomas) are rare in the pediatric population. The physician needs to have a high degree of suspicion for such lesions if a child presents with ear pain unrelated to infection or otorrhea that fails to improve after treatment. A precise diagnosis needs to be made in these children and also in those with hearing loss, vertigo, and facial paralysis. The most useful imaging procedures for ear, temporal bone, and CPA masses are CT and MR imaging. With a suspected vascular lesion, a definitive diagnosis usually can be made by an imaging procedure or angiography. In all cases of mass lesions, except for some aneurysms and infections, a tissue diagnosis must be secured. PMID- 1442314 TI - Lyme disease: ecology, epidemiology, clinical spectrum, and management. PMID- 1442315 TI - Helicobacter pylori, gastritis, and ulcers in pediatrics. AB - Hp now appears to be more than a simple commensal organism in patients with gastritis or peptic ulcer disease. Microbiologic, serologic, and epidemiologic studies all confirm that Hp has an important role in children with abdominal pain. Hp is found in the gastric mucosa of children with histologically proven gastritis or peptic ulcer. The organism can be transmitted from human to human with evidence of colonization, appearance of gastritis, and serum antibody response. Antimicrobial therapy directed at Hp eradicates colonization and resolves symptoms. Hp antibodies appear more frequently in familial clusters and the frequency of antibody positivity increases with age. Children are more likely to have symptomatic disease associated with elevated antibody titers. Recurrence of disease is associated with reappearance of the organism. At the present time, colonization can be detected only by gastric biopsy; however, it may be possible eventually to diagnose or follow infections by obtaining serum antibody titers or urea breath-testing. The natural history of Hp infection is unclear. Although it can cause an acute gastritis, it generally is found in association with chronic gastritis. The increase in seropositivity with age may mean that slow changes evolve over decades or that age cohorts have been infected differentially. How does antral colonization with Hp cause duodenal ulceration? The organism is not found in the duodenum and most patients with gastritis do not develop ulcers. This may be related to changes in acid production and mucosal protection associated with Hp colonization, but few studies have been done. What factors initiate Hp infection? Both volunteers who became colonized first suppressed acid secretion with H2-antagonists. Hypochlorhydria also seems to follow Hp infection in these same studies. The role of diet and drugs, or other environmental and genetic factors, in initiating infection is largely unexplored. An effective means of therapy needs to be developed. Although Hp appears sensitive in vitro to many compounds, it is difficult to eradicate in vivo, especially with monotherapy. Single-drug therapy suppresses the organism, but recurrence rates are high. It is difficult to deliver effective doses of drugs to the mucous niche the organism has selected and concerns about long-term therapy and its side effects persist. Current data suggest no ready solution to the initial case presentation. A child with primary gastritis or duodenal ulcer should be treated first with standard antacid and H2-receptor antagonist therapy. If endoscopy is performed, biopsies of normal-appearing areas of gastric antrum should be stained for Hp and a biopsy urease test should be performed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1442316 TI - Newborn screening for cystic fibrosis. The Cystic Fibrosis Neonatal Screening Study Group. AB - Many questions remain regarding the efficacy, risks, and costs of CF neonatal screening. The major gap in knowledge that must be closed before CF neonatal screening can be recommended generally in the United States concerns the potential long-term medical benefits of initiating treatment in early infancy. It would be premature, in our opinion, to implement mass population screening of newborns for CF until the benefits and risks have been fully defined, and an adequate and logistically feasible testing system developed and/or highly effective therapy for CF lung disease becomes available. It is for this reason we designed a randomized, controlled investigation of CF neonatal screening and implemented this project in Wisconsin during 1985. The fact that 5 years of randomized screening and systematic evaluation of outcome measures have not yet revealed any pulmonary benefits underscores the importance of rigorous investigation to resolve the efficacy issue. In addition to the medical uncertainties, we believe that the ethical issues described herein need to be resolved; this concern pertains not only to the CF patient but also the heterozygote carrier. On the other hand, financial factors and uncertainty about the cost effectiveness of CF neonatal screening do not appear to be dominant issues according to our assessment of current data. Despite the reservations related to the benefit/risk relationship, we expect that the discovery of the CF gene should have a favorable impact on neonatal screening for the disease, as well as for management. PMID- 1442317 TI - Neonatal hemochromatosis. PMID- 1442318 TI - Protein and energy during weaning. PMID- 1442319 TI - Pediatric renal transplantation. PMID- 1442320 TI - Intravenous immunoglobulin in the prevention and treatment of neonatal bacterial sepsis. AB - IVIG has been shown in vitro to enhance many antibody-dependent immunologic functions. In animal models, IVIG enhanced the survival of septic neonates. In humans, preliminary data indicate that prophylactic IVIG may diminish the incidence of bacterial sepsis in VLBW neonates if sufficient doses of the immunoglobulin are administered repeatedly. IVIG administered after the onset of clinical symptoms may improve the survival of septic human neonates. However, the studies designed to assess the efficacy of IVIG to treat established sepsis have employed a small number of subjects and have, overall, provided inconclusive data. IVIG has been tolerated well by neonates, but the safety and long-term consequences of administering IVIG to newborn infants are not yet defined. IVIG will likely serve as a useful adjunct to enhance the antibacterial defenses of newborn infants. Use of IVIG in human neonates remains experimental at this time; therefore, the clinical application of IVIG for the prevention or treatment of neonatal bacterial sepsis should await the development of guidelines to be derived from ongoing multicentered, placebo-controlled clinical trials. PMID- 1442321 TI - Biochemical, structural, and molecular genetic aspects of halophilism. PMID- 1442322 TI - Proton nuclear magnetic resonance studies on hemoglobin: cooperative interactions and partially ligated intermediates. PMID- 1442323 TI - Thermodynamics of structural stability and cooperative folding behavior in proteins. PMID- 1442324 TI - Structure and stability of bovine casein micelles. PMID- 1442325 TI - Dietary manipulation in experimental inflammatory bowel disease. AB - Eicosanoids are major mediators of defensive and inflammatory processes of the gut mucosa. The activity of the eicosanoid system is modulated by neural and hormonal pathways, but local factors acting within the gastrointestinal lumen may also be involved. We have studied the influence of dietary fatty acids on eicosanoid synthesis by the gastrointestinal mucosa. Since omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower or cod liver oil as sources of omega-6 or omega-3 fatty acids, respectively. Rats fed with the cod liver-oil-supplemented diet for four weeks showed high omega-3 and low omega-6 plasma fatty acid levels compared to rats fed with the sunflower oil diet. Synthesis of arachidonic-acid-derived eicosanoids (6-keto-PGF1 alpha, PGE2, TXB2, LTB4, and LTC4) by gastric and intestinal mucosa was found to be lower in the cod liver group as compared to the sunflower group. However, significant generation of eicosapentaenoic-acid-derived eicosanoids (PGE3 and LTC5) was observed only in the cod liver group. We used the (trinitrobenzenesulphonic acid) TNBS model of inflammatory colitis to test the effect of the dietary fat on the development of inflammatory lesions of the bowel. A single intracolonic instillation of the hapten TNBS dissolved in 10% ethanol induces chronic granulomatous lesions of the colonic mucosa that persist for up to 8 weeks. Luminal release of eicosanoid mediators, as measured by intracolonic dialysis, was lower in the cod liver group than in the sunflower group, particularly during the chronic stage of the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442326 TI - Effect of non-steroidal anti-inflammatory drugs on glutathione levels in various organs of rat. AB - Since glutathione (GSH) depletion (about 20% of total GSH content) can impair the cell's defence against the toxic actions of drugs and may lead to cell injury and death, we examined the effect of piroxicam, naproxen and ketoprofen on GSH levels in various organs of the rat (brain, eye, liver, stomach, heart, leg adductor muscle). Ketoprofen in brain and leg adductor muscle dramatically decreases the GSH levels, giving rise to potential cellular toxicity. PMID- 1442327 TI - Use of the rat air pouch model of inflammation to evaluate regional drug delivery. AB - We have used the rat inflammatory air pouch model to investigate some of the pharmacokinetic and pharmacodynamic issues relating to regional drug delivery. S(+)Ibuprofen was administered either intravenously or directly into the air pouch at the same time as the irritant (carrageenan). Serial samples of exudate and plasma were then taken and assayed for drug concentrations and various efficacy markers. Ibuprofen given intrapouch, was found to inhibit in a dose dependent manner the concentration of prostaglandin E2 and the number of white cells in the exudate. Plasma and pouch concentration-time profiles are described for s(+)Ibuprofen: there is evidence for greater drug retention in the pouch than in plasma following regional and systemic delivery. PMID- 1442328 TI - Desferrioxamine potentiated SOD antiinflammatory activity in rat adjuvant arthritis: role of iron and bacterial toxins. AB - In this paper we studied the modulating inflammatory activity of iron in the adjuvant arthritis, taking indomethacin as a standard antiinflammatory drug and a superoxide dismutase derivative (MPEG-SOD) as a scavenger of free radicals. Moreover, we evaluated the changes in potential intestinal pathogens requiring iron for growth, in order to study the role of bacteria in the altered gastrointestinal functions observed during arthritis. We observed a 50% arthritis inhibition on the 14th day with MPEG-SOD plus desferrioxamine, a significant decrease in serum iron in arthritic rats compared to controls, and a significant Cl. perfringens increase on the 28th day in the presence of MPEG-SOD. Our data demonstrate that hypoferremia, in arthritis, is a protective mechanism overall in the early phase and could protect the intestinal tract by inhibiting the development of potential pathogens. PMID- 1442329 TI - Anti-inflammatory effect of tuftsin and its retro-inverso analogue in rat adjuvant arthritis. AB - Tuftsin, an immunostimulating tetrapeptide derived from immunoglobulin heavy chain, and its retro-inverso analogue have been tested in rat adjuvant arthritis. The secondary lesion of rats injected with Freund's adjuvant was significantly inhibited by both the natural and retro-inverso tuftsin administered orally. The retro-inverso analogue was at least tenfold more potent than the parent molecule, suggesting an increased stability to degradation, because of its molecular modification. The anti-inflammatory effect of tuftsin may be due to its ability to modulate macrophage function. PMID- 1442330 TI - Copper supplementation in the rat: preliminary observations on the clinical, hematological and histopathological profile. AB - Complete toxicological examinations in female rats fed an "anti-inflammatory" 200 ppm copper-containing diet for 30 and 58 days were performed. Copper was found to accumulate in liver, kidneys and paws; however, at the hematological, clinical chemical and histopathological levels, this treatment did not seem able to induce any toxic accumulation phenomenon in the examined rats. PMID- 1442331 TI - Time- and dose-related influence of dexamethasone on morphine-induced hypermotility in mice. AB - The effect of interaction between dexamethasone (DEX) and morphine on locomotor activity in mice was investigated. DEX alone (1.0 and 10 mg/kg i.p.) did not affect the locomotor activity of mice when injected immediately before the beginning of the session. DEX (1.0 mg) injected two hours before the session did not modify the activity of mice whereas the higher dose (10 mg) increased it. Morphine alone (30 mg/kp i.p.) induced a consistent increase in the locomotor activity. DEX (1.0 mg) injected at the same time as morphine reduced the morphine hypermotility, whereas that injected two hours before morphine had no influence on morphine hypermotility. DEX (10 mg) consistently potentiated the morphine hypermotility both when administered together and two hours before morphine. We conclude that DEX exerts an important time- and dose-related influence on morphine-induced hyperactivity in mice. PMID- 1442332 TI - Indomethacin-induced enteropathy: effect of the drug regimen on intestinal permeability in rats. AB - To set up and characterize reproducible, long-standing small intestinal inflammation in rats, animals were given three different oral regimens of indomethacin (Ind): a bolus of 10 mg/kg in water and three daily doses of 2, 4, and 8 mg/kg Ind in (a) the drinking water or (b) the standard diet. The effect of Ind on the small intestine was monitored by measuring intestinal permeability (IP). The three-day regimen seemed more suitable than a bolus dose to induce long standing inflammatory modifications in the rat small intestine and Ind administered in the drinking water gave more consistent modifications of IP and more reproducible results than Ind in food. IP seemed a suitable tool for detecting these inflammatory changes in the small-intestinal physiology. This model could be used to assess the effect of new drugs on inflammation. PMID- 1442333 TI - Immunological aspects of inflammatory bowel diseases of the human gut. AB - The gut has a highly specialized immune apparatus, particularly involving the production of protective secretory immunoglobulin A (IgA), but also involving T cell immunity. Secretory IgA plays a major role in preventing antigen uptake, both of infectious and non-infectious types. IgA immune responses are initiated by antigen uptake into specialized lymphoid aggregates such as Peyer's patches, and IgA plasma cell precursors are subsequently distributed throughout the gut and also over other mucosal surfaces. The clinical consequences of perturbation of the local immune system of the gut are surveyed in this article, including the consequences of immunodeficiency and the conditions reflecting an enhanced expression of immunity in the gut mucosa. The potential impact of non-steroidal anti-inflammatory drugs on the local immune system is discussed. PMID- 1442334 TI - Role of Helicobacter pylori in gastritis and duodenitis in man. AB - Although Helicobacter pylori is now accepted as the major aetiological factor in chronic gastritis in man, many of the factors which determine its pathogenicity are unknown. The organism has adapted to survive in the low-pH environment of the stomach, partly through its ability to buffer hydrogen ion by the hydrolysis of urea and by the presence of lectins on its surface, which bind to gastric mucosa and epithelial cells. After attachment, harmful toxins and enzymes have access to the gastric cells and cellular damage and an immune response ensues. In patients with duodenal ulceration, Helicobacter pylori-related gastritis predominantly affects the gastric antrum and has a high prevalence. Excessive gastrin production has been suggested as a potential aetiological factor linking infection with duodenal ulcer development. Perhaps more important is the association between gastric metaplasia of the duodenal epithelium, which is correlated with acid load and is more extreme in H. pylori positive patients with duodenitis. Organisms may subsequently spread from the gastric antrum into areas of gastric metaplasia in the duodenal bulb, leading to areas of chronic duodenitis and ultimately frank ulceration. It should not be overlooked, however, that other factors such as genetic predisposition, blood group, stress, drugs and smoking all have a role to play in the outcome, given the comparatively small number of patients in the general population infected with H. pylori who develop ulcer disease. PMID- 1442335 TI - Interleukin 1 beta (IL-1 beta) release from fresh and cultured colonic mucosa in patients with ulcerative colitis (UC). AB - Interleukin-1, a cytokine produced by macrophages and other tissue cells, has a major role in inflammatory and immunological responses. Increased levels of IL-1 activity have been reported in experimental colitis and in patients with active Crohn's disease (CD) and ulcerative colitis (UC). IL-1 beta release from fresh and cultured colonic biopsies and IL-1 beta plasma concentrations was determined in 15 patients with active UC, 16 with UC in remission and 10 normal control subjects. Biopsies, taken at colonoscopy were weighed, washed in 1 ml of 0.9% sodium chloride solution and then cultured for 24 h in 10% fetal calf serum/RPMI. IL-1 beta activity was determined by ELISA KIT (Cystron Biotechnology) in plasma samples, washing solution and the incubation medium. Very low levels of IL-1 beta were detected only in 3 plasma samples, all from active patients. Significantly more IL-1 beta was released from fresh and cultured colonic mucosa obtained from patients with UC in remission compared to normal mucosa (p less than 0.01). Furthermore, specimens from active UC released significantly more IL-1 beta than those from patients in remission (p less than 0.01). In conclusion, IL-1 may play an important role in mediating the inflammatory response in UC. PMID- 1442336 TI - 15-HETE is the main eicosanoid formed by human colonic mucosa. AB - Eicosanoids were measured in colonic biopsies from eleven patients with active ulcerative colitis and from thirteen controls. Eicosanoid formation was measured after the addition of arachidonic acid and stimulation with calcium ionophore A23187. The 15-lipoxygenase derivative 15-hydroxy-eicosatetraenoic acid (15-HETE) was the predominant product formed in all biopsies. The amount of 15-HETE formed was dependent on the site of biopsy and decreased in the controls in biopsies taken in an aboral direction in the colon. The formation of 15-HETE and that of prostaglandin E2 (PGE2) and PGF2 alpha was proportional to the histologically obtained inflammation score. The role of 15-H(P)ETE as a mediator in ulcerative colitis should, therefore, be considered in addition to the effects of known modulators such as leukotriene B4 (LTB4) and PGE2. PMID- 1442337 TI - Treatment of the mucosa with local anaesthetics in ulcerative colitis. AB - A new paradigm for the treatment of ulcerative colitis has recently been presented: Treatment of the mucosa with lidocaine (2%) enemas for prolonged periods. This therapy was introduced based on the hypothesis that hyperreactive autonomic nerves may play a pathogenetic role in the disease. One hundred consecutive patients have now been treated and the results presented. The proctitis patients all responded to the treatment, despite previous therapeutic failures in more than two-thirds of the cases. They were treated for 3-12 weeks, but 68% had a relapse (observation period 20 months). Of the 49 patients with proctosigmoiditis, two-thirds had chronic symptoms resistant to previous therapy. One of these patients did not respond to lidocaine, but developed fulminant total colitis. The other patient had therapeutic failure with lidocaine but responded well to subsequent cortisone enemas. The patients were treated until the subsets of T-lymphocytes (OKT4+ and OKT8+) disappeared from the mucosa. This occurred in parallel with symptomatic relief and eventual healing in 83% of the patients after treatment for 6-34 weeks. Of all the patients with proctosigmoiditis, 42% presented with recurrent symptoms (observation period 16 months). Of the 17 patients with left-sided colitis, all went primarily into remission within 2-4 months, but 23% had a relapse (observation period 13 months). The 6 patients with total colitis had symptomatic relief and improvement of histology when treated over 3-8 months. One patient had recurrence after 12 months. Treatment with a local anaesthetic in ulcerative colitis is a new approach to mucosal inflammation. The beneficial effects may be due to blockade of certain neural effects, such as epithelial proliferation and shedding and congestion of the mucosal vasculature, with actions on cells of the immune system. PMID- 1442338 TI - Species differences in the pattern of eicosanoids produced by inflamed and non inflamed tissue. AB - The synthesis of 14C labelled arachidonic acid metabolites was measured in colonic tissues obtained from mice, rats, guinea pigs, rabbits, piglets and in colonic biopsies from humans during colonoscopy. The main eicosanoids formed after stimulation with calcium ionophore A23187 were: in humans, 15-hydroxy eicosatetraenoic acid (15-HETE); in mice, 12-HETE; in rats, 12-HETE, 12-hydroxy 5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandin F1 alpha (6kPGF1 alpha); in guinea pigs, PGD2; in rabbits, 6kPGF1 alpha, PGE2 and 15-HETE; and in pigs PGE2 and 12-HETE. In inflamed 15-HETE production was increased in man, HHT and 12-HETE production in rats and overall eicosanoid production in mice. PMID- 1442339 TI - Experimental colitis in mice: effects of olsalazine on eicosanoid production in colonic tissue. AB - In rodents colitis can be induced by adding 2% (w/v) carrageenan (CARR) for 4 weeks or 10% (w/v) dextran sulphate sodium (DSS) for 7 days to their drinking water. These models are suitable to test anti-inflammatory drugs used in inflammatory bowel disease in man. Mice were treated with olsalazine (400 mg/kg body wt) starting 7 days before the DSS or CARR administration. Colonic tissues were incubated with [1-14C]-arachidonic acid and stimulated with A23187 and, thereafter, the pattern of eicosanoids was determined by separation on HPLC. DSS and CARR produced a marked diffuse inflammatory response in the colon and a subsequent 5-fold increase of all eicosanoids after DSS, whereas after CARR only a 2-fold increase of PGs was observed. Olsalazine treatment decreased all cyclooxygenase and lipoxygenase products to baseline levels. PMID- 1442340 TI - Anti-inflammatory and gastrointestinal effects of nabumetone or its active metabolite, 6MNA (6-methoxy-2-naphthylacetic acid): comparison with indomethacin. AB - 6MNA, the active metabolite of the non-acidic anti-inflammatory drug nabumetone, was investigated using intravenous administration for effects on (a) carrageenan paw oedema and gastric irritancy compared to either oral nabumetone or both oral and intravenous indomethacin when given acutely and (b) gastrointestinal irritancy when given in repeat dosing studies. An oral dose of nabumetone or intravenous 6MNA produced effective anti-inflammatory activity together with significant inhibition of paw exudate PGE2. An anti-inflammatory oral dose of nabumetone or intravenous 6MNA produced minimal effects on gastric 6-keto-PGF1 alpha production, with an absence of gastric damage, in contrast to indomethacin. In repeat dose studies, 6MNA failed to induce gastrointestinal damage even at doses where general toxicity was evident. These results show that in the rat 6MNA, the active metabolite of nabumetone, is an effective anti-inflammatory drug but, even in very high intravenous doses, does not have the propensity to induce gastrointestinal damage. PMID- 1442341 TI - EM 405: a new compound with analgesic and anti-inflammatory properties and no gastrointestinal side-effects. AB - EM 405 has analgesic and antitussive effects, probably exerted by noradrenaline uptake inhibition and local anaesthetic actions. It showed anti-inflammatory, which may be due to anti-histaminic and indirect sympathomimetic properties. As oral application of EM 405 did not induce gastrointestinal side effects a possible ulcer preventing action was investigated. EM 405 reduced gastric ulcers induced by ethnology or indomethacin with ED50 values of 45 and 26 mg/kg p.o. Stress-induced ulcer was inhibited with an ED50 of 34 mg/kg. EM 405 reduced basal and stimulated gastric secretion by reducing volume as well as H(+)- and Cl(-) production. Therefore ulcer prevention by EM 405 may be explained by its inhibitory effects on gastric secretion. The results characterise EM 405 as a novel anti-inflammatory compound with ulcer-protective action. PMID- 1442342 TI - Gastrointestinal bleeding associated with the use of non-steroidal, anti inflammatory drugs--symptomatology and clinical course. AB - The symptoms associated with admission for gastrointestinal haemorrhage were studied in relation to the intake of non-steroidal, anti-inflammatory drugs (NSAIDs) within fourteen days prior to admission. In a prospective, two-year study we included only those with bleeding due to gastroduodenal ulcers or haemorrhagic erosive gastritis. In 94 patients with a median age of 74 years, NSAID use was stated in 54, but the symptoms in these subjects (degree of epigastric pain, nausea or heartburn) were no different from those without previous NSAID use. Correspondingly, no difference was seen as to the clinical course of the bleeding. PMID- 1442343 TI - Effect of sulglycotide treatment on cell kinetics alterations induced by aspirin in humans. AB - The effect on gastric epithelial cell proliferation of small doses of aspirin was evaluated in 9 healthy volunteers, with or without administration of sulglycotide, a sulfated glycopeptide with cytoprotective properties. Cell kinetics study was performed by incubation of gastric biopsies with bromodeoxyuridine (BrdU) and immunohistochemistry. A decrease of BrdU-labeling index and a shortening of the height of gastric columns were observed after treatment with aspirin and placebo. No variations were observed after treatment with aspirin and sulglycotide. A decrease of the epithelial cell renewal could be one of the damaging effects of aspirin on the gastric mucosa. The treatment with sulglycotide seems to be effective to prevent this alteration. PMID- 1442344 TI - Influence of steroid treatment's duration in patients with active Crohn's disease. AB - Steroids are very useful drugs in the treatment of active Crohn's disease (CD), but clinical relapses after steroid withdrawal may be very high. We investigated the efficacy of two steroid regimens of different duration in inducing remission and in maintaining it after drug suspension. Patients with active CD were randomly assigned to scheme A, lasting 7 weeks (27 patients), or to scheme B, lasting 15 weeks (27 patients). Remission rates at the end of the treatment were 81% for scheme A and 85% for scheme B. Relapse rates at 6 months after stopping the treatment were 50% (11 patients) and 52% (12 patients), respectively. Remission rates seem not to be influenced by the duration of the treatment, but patients recently treated with steroids showed a higher relapse rate if they received the short-duration treatment. PMID- 1442345 TI - Vasodilator therapy enhances neutrophil tissue migration. AB - Very little is known about the effect of vasoactive substances on migration of polymorphonuclear neutrophils in vivo. We evaluated the effect of oral treatment with isosorbide dinitrate on neutrophil migration into a sterile skin inflammatory focus in man with the use of "skin chamber technique". Isosorbide dinitrate increased the number of neutrophils harvested in the chamber as well as the "granulocyte clearance". Thus, vasoactive agent may increase neutrophil extravasation and subsequent tissue migration. PMID- 1442346 TI - [Quantitative estimation of the relationship between amino acids and cataracts in rat lens]. AB - The concentration of free amino acids and their related compounds has been determined in the lenses of ICR (f) strain rat and in the Wistar strain rat's lenses which were cultured with diethyl maleate. It was supposed that the decrease of cystathionine and the increase of serine in lenses of ICR with aging were related with development of senile cataracts. The increase of cystathionine in lenses cultured were suggested that synthesis of taurine is done by cystathionine pathway. Quantitative changes of amino acids were higher than normal of glutamine, glycine and aspartate in lenses cultured. It was supposed that the changes were the flow in lens from medium for synthesis of glutathione and glucose. PMID- 1442347 TI - [Anticoagulant and fibrinolytic therapies for anterior chamber fibrin following cataract surgery in the rabbit eye]. AB - Effects of anticoagulant or fibrinolytic therapy on anterior chamber fibrin following cataract surgery was evaluated. In one series of experiment, various amounts of antithrombin III (ATIII), an anticoagulant, were injected into the anterior chamber of the rabbit eye immediately after phacoemulsification of the lens. In another series, various amounts of tissue plasminogen activator (TPA), a fibrinolytic agent, were injected into the anterior chamber 24 hours after phacoemulsification when it was filled with fibrin. The extent of the fibrin clot was graded using a slit lamp microscope, and the aqueous flare intensity was determined with a laser cell-flare meter for 2 weeks after operation. The eyes treated with TPA was also examined with light and electron microscopy. ATIII showed an inhibitory effect on fibrin formation, but complete inhibition was not obtained even with the highest concentration used. In contrast, the fibrin clot was completely resolved even with the lowest dose of TPA used, while no side effect such as inflammation or bleeding was seen. Histological examinations revealed no pathological changes in eyes treated with TPA. TPA may be a promising agent for fibrin resolution after cataract surgery. PMID- 1442348 TI - [Changes in retinal blood flow volume in experimental retinal vein compression]. AB - The authors quantitated the retinal blood flow volume during and immediately after experimental compression of the temporal retinal vein in 5 Macaca fuscata monkey eyes. The hydrogen clearance method was used to quantitate the retinal blood flow volume. After placing a microelectrode on the retinal surface, we measured the blood flow volume 4 times at a 15-minute interval. This value served as a baseline for the experiments. Next we compressed the temporal retinal vein near the disc with a 25-gauge needle with a rounded tip under guidance by an indirect ophthalmoscope. We measured the blood flow volume during compression. The compression was maintained for 3 minutes. Further blood flow determination was performed 7 minutes after release of compression and was repeated 4 times at a 15-minute interval. During compression of the temporal retinal vein, the retinal blood flow volume in the area served by the vein decreased by an average of 35%. The flow volume recovered rapidly and remained stable after release of compression. There was no reactive hyperemia. This model appears useful to elucidate the retinal circulation of branch retinal vein occlusion. PMID- 1442349 TI - [Retinal toxicity of intravitreally injected steroids on the rabbit eye]. AB - The retinal toxicity of intravitreally injected steroids, fluorometholone and tetrahydrocortisol, was examined. The concentration of the steroids was 20 mg/ml, and 0.05 ml of each solution were injected into the rabbit vitreous cavity. An equal volume of saline solution was injected as a control. In addition to ophthalmoscopy, intraocular pressure was measured and electroretinography, light microscopy and electron microscopy were performed. The results showed no remarkable changes in all eyes. Fluorometholone and tetrahydrocortisol seem to have neither toxicity to the retina nor adverse effect of elevating intraocular pressure when intravitreally injected with this amount. PMID- 1442350 TI - [Ocular effects of topical instillation of UF-021 ophthalmic solution in healthy volunteers]. AB - Phase I studies, as divided into two stages, were conducted in healthy volunteers with the ophthalmic solution of UF-021, a novel prostaglandin metabolite-related compound, that was reported to exhibit potent intraocular pressure (IOP)-reducing activity in various species of animals. In the first stage, the vehicle as well as UF-021 ophthalmic solutions at concentration of 0.03%, 0.06% and 0.09% were applied topically to the eyes of 8 healthy volunteers to determine their respective effects through observations on the IOP, and local ocular and systemic side effects. In the second stage, 2 dosages of UF-021 ophthalmic solution, 0.06% and 0.12%, were applied topically to 11 healthy volunteers to investigate the IOP reducing activities and local ocular side effects. The results revealed that ophthalmic solutions of UF-021 at concentrations ranging from 0.03% to 0.12% reduced IOP in a dose-dependent manner with neither systemic nor local ocular controversial side effects at those dosage levels. In summary, UF-021 ophthalmic solutions, when administered to healthy volunteers through single instillation, reduced IOP significantly without causing any side effects. PMID- 1442351 TI - [Accommodative resting position and the effect of viewing distance on after effects of accommodation and the pupil]. AB - The resting position of accommodation is determined by the equilibrium established between sympathetic and parasympathetic tone. To accommodate for near objects is brought about by excitation of the parasympathetic, and distant objects call for excitation of the sympathetic system. To investigate accommodation and pupil after-effects following the 10 min visual task with stereoscopic three dimensional image, the measurements of the dynamic responses of accommodation and pupil were made. When the subjects worked at 0.4 m (closer than their resting state) and at 1 m corresponded to their resting positions, the response delay in accommodative relaxation occurred in each condition. When they worked at outside their resting position (1.5 m and 3 m viewing distances), the significant response delay in contraction in the groups of 1.5 m and 3 m, and the increases of accommodation error and the area of miosis were shown. There was a fact that the after-effect on accommodation and pupillary function was different between in the case of tasks given inside and outside their resting positions. PMID- 1442352 TI - [Intraocular lens implantation after glaucoma filtering surgery--time course of changes in intraocular pressure control and filtering blebs]. AB - Cataract extraction and intraocular lens (IOL) implantation were carried out in 45 glaucomatous eyes that had undergone glaucoma filtering surgery. Of these, 37 eyes had primary glaucoma, 2 eyes capsular glaucoma, and 6 eyes secondary glaucoma. The visual acuity after IOL implantation was 0.5 or more in 29 eyes (64%) but in 10 eyes (22%) acuity was 0.1 or less because of advanced optic nerve head damage. To analyze affects of IOL implantation on intraocular pressure (IOP) control and functioning of the filtration bleb in 39 eyes of primary or capsular glaucoma, a life-table analysis with the Kaplan-Meier method was performed. The probability that IOP control does not worsen at 2 years was 43 +/- 7% (SE) in 21 eyes without pre-operative ocular hypotensive medication, 56 +/- 16% in 18 eyes with pre-operative ocular hypotensive medication, 47 +/- 12% in 26 eyes where functioning filtering bleb existed pre-operatively. The probability that the filtering bleb survives 2 years post-operatively was 44 +/- 11%. The present results imply that intensive management of post-operative inflammation and careful IOP follow up are imperative in eyes in which IOL implantation was indicated after undergoing filtration surgery. PMID- 1442353 TI - [Enhanced production of in vitro tumor necrosis factor-alpha from monocytes in Behcet's disease]. AB - In vitro tumor necrosis factor-alpha (TNF-alpha) production from peripheral blood monocytes (PBMC) was investigated among 12 patients (male: 7, female: 5) with uveoretinitis of Behcet's disease and 6 age-matched healthy controls. TNF-alpha production of PBMC after the stimulation with lipopolysaccharides (LPS) was significantly enhanced in Behcet's disease patients with active uveoretinitis (21.5 +/- 2.8 U/ml) compared with both controls (5.7 +/- 1.8 U/ml) (p < 0.01) and inactive cases (5.1 +/- 1.4 U/ml) (p < 0.01). In the cases with active uveoretinitis, TNF-alpha production in the period of ocular attack (7.2 +/- 6.2 U/ml) was significantly lower than that of the post-attack period (24.4 +/- 13.9 U/ml) (p < 0.02). These results may indicate that TNF-alpha plays an important role in the immunopathogenesis of uveoretinitis in Behcet's disease. PMID- 1442354 TI - [Antibody titer to streptococcal and staphylococcal L-form in Behcet's disease and other uveitis]. AB - The antibody titer in serum to Streptococcus pyogenes L-form and Staphylococcus aureus L-form were determined by enzyme-linked immunosorbent assay in 28 patients with Behcet's disease, 31 patients with other uveitis (sarcoidosis: 10, Harada's disease: 5, tuberculosis: 4, rheumatoid arthritis: 4, lues: 2, juvenile rheumatoid arthritis: 2, herpes simplex: 2, trauma: 2) and 16 healthy normal controls. All L-forms were induced by the penicillin disk method. The antibody titer to Streptococcus pyogenes L-form in Behcet's disease was lower than that of other cases of uveitis and controls, and showed significant differences between controls, rheumatoid arthritis, sarcoidosis, tuberculosis and Harada's disease by the Student's t-test. The antibody titer to Staphylococcus aureus L-form in Behcet's disease showed no difference between controls and other cases of uveitis. In each uveitis and controls, and between active and inactive stages of all uveitis, there were no differences between titers. In Behcet's disease, antibody formation to Streptococcus pyogenes L-form may be specifically disturbed. PMID- 1442355 TI - [Low dose cyclosporin treatment for ocular lesions of Behcet's disease]. AB - Cyclosporin is an immunosuppressant that has recently been used for the treatment of Behcet's disease. We evaluated the clinical effect of low doses of cyclosporin (5 mg/kg/day) on 20 patients of Behcet's disease with refractory ocular involvement. The therapeutic effect of cyclosporin was judged by the frequency of ocular inflammatory attacks. It was effective in more than 70% of the patients. On the other hand, it had some adverse side effects such as renal dysfunction, indigestion, and neurological disorders. Most side effects were mild with low dose treatment, but neurological side effects were similar in frequency and severity to those seen with 10 mg/kg/day usage. These findings indicate that low dose cyclosporin (5 mg/kg/day) administration may be acceptable as a standard plan for treatment of Behcet's disease, but that we have to use cyclosporin with great attention to its side effects, especially neurological symptoms. PMID- 1442356 TI - [pO2, pCO2 and acid-base balance in the human vitreous sample]. AB - In order to clarify the physiological profile in vitreous cavity undergoing vitrectomy, both human vitreous and venous blood samples were obtained to measure pO2, pCO2, acid-base balance and potassium. A new collection system was employed to obtain vitreous samples from 15 eyes under local or general anesthesia. The mean vitreous pO2 was higher than that of venous blood, and was affected by irrigative air more than breathed oxygen. Irrigating air was considered to be one of the best methods to supply enough oxygen concentration to the inner retina during the vitrectomy. Although the vitreous pH showed alkalosis during the air irrigation, it was suggested that to protecting the retina, the vitreous bicarbonate buffer was not enough to compensate for the decrease in the vitreous pH. PMID- 1442357 TI - [Postoperative anterior chamber inflammation after posterior chamber intraocular lens implantation concurrent with pars plana vitrectomy and lensectomy]. AB - The authors compared postoperative anterior chamber inflammation of triple procedure; diabetic pars plana vitrectomy, lensectomy with anterior capsule left intact and posterior chamber intraocular lens implantation anterior to anterior capsule, to those of various cataract surgeries with posterior chamber intraocular lens implantation and vitrectomies in diabetic retinopathy eyes. The inflammation was evaluated in terms of the incidence of inflammatory complications (fibrin reaction and posterior synechia of iris), and by periodical measurement of flare counts for postoperative 6 months using a laser flare-cell meter. The inflammation was more intense than those after the following 3 surgeries; phacoemulsification and in the bag intraocular lens implantation after continuous curvilinear capsulorhexis, extracapsular extraction and in the bag intraocular lens implantation after can opener capsulotomy, and vitrectomy alone. The inflammation, however, was less intense compared with that of another method of triple procedure; pars plana vitrectomy, phacoemulsification and in the bag intraocular lens implantation after continuous curvilinear capsulorhexis or can opener capsulotomy, and development of posterior synechia was rarely observed. PMID- 1442358 TI - [Clinical study of venous abnormalities in diabetic retinopathy]. AB - The authors studied 304 eyes (248 cases) affected by diabetic retinopathy in relation to venous abnormalities by ophthalmoscopy, slit lamp examination with contact lens and fluorescein angiography. The posterior pole and surrounding mid peripheral area were examined. The subjects consisted of 225 eyes with pre proliferative and 79 eyes with proliferative retinopathy. Fifty-six eyes (18%) had venous abnormalities: 17 of the 225 eyes (8%) with pre-proliferative retinopathy and 39 of the 79 eyes (49%) with proliferative retinopathy. In the 56 eyes with venous abnormalities. 39 (96%) showed beading. 14 (25%) showed looping and 2 (4%) showed duplication. All eyes which showed looping or duplication had proliferative retinopathy. The locations of the venous abnormalities were analyzed: 42% were in secondary branches, 27% in tertiary branches, 18% in primary branches, 10% in fourth branches and 3% in fifth branches. The portion of the fundus affected was upper temporal, lower temporal, upper nasal and lower nasal in 28%, 22%, 29% and 21%, respectively. Based on our results, eyes with looping or duplication on ophthalmoscopic or slit lamp examination, have an extremely high probability of being in some stage of proliferative retinopathy. Retinopathy should be confirmed by fluorescein angiography and photocoagulation should be performed as quickly as possible. PMID- 1442359 TI - [Analysis of optic nerve head circulation in diabetics using a laser Doppler technique]. AB - The authors measured the red blood cell speed distributions in the capillaries of the optic nerve head using a laser Doppler technique. We calculated the widths of Doppler-broadened frequency spectra of laser light scattered from temporal sites on the optic nerve head in 34 Type I diabetic patients (mean age, 29.5 years; 12 patients having no retinopathy; 22 having background retinopathy) and in 29 age- and sex-matched normal controls. Doppler broadening proportional to the red blood speed was 763 +/- 113 Hz (mean +/- SD) in the diabetics and 912 +/- 167 Hz in the controls. The difference was statistically significant. Mean blood pressure and intraocular pressure in the diabetics were not significantly different compared to controls. Our finding of abnormally low capillary blood speeds suggests that pathologic alterations occur in the microvasculature of the optic nerve head in the early stages of diabetic retinopathy. PMID- 1442360 TI - [Age-related changes in the normal visual field using colored targets]. AB - The authors evaluated the influence of aging on the normal visual field sensitivity and the color visual field sensitivity. The central 5 degrees visual field of 259 normal subjects (ages 10 to 79) was evaluated with Program Macula of the Humphrey Field Analyzer. Visual field sensitivity remained constant, irrespective of age, until 40 years. In contrast, sensitivity decreased linearly with aging after 40 years. The age-related decline of visual field sensitivity was most remarkable using a blue target. Visual field sensitivity gradually decreased toward the peripheral retina measured by white, red and green targets. However, using a blue target, at 1 degree-2 degrees locations from the fovea, sensitivity was the same as foveal sensitivity. There were no statistically significant differences of visual field sensitivity between the lower half of visual field and the upper half, and between the temporal half and the nasal half. At all test locations, the ordering of visual field sensitivity was white > red > blue > green target. PMID- 1442361 TI - [A telescopic system for distance consisting of contact lens and spectacle lens for low vision patients]. AB - A telescopic system for distance consisting of a negative contact lens (-10.0 - 20.0 D) as the eye piece and a positive spectacle lens (+8.0 - +16.0 D) as the objective, a modification of the Galilean telescope was examined. First the system was tried in 15 normal subjects, whose visual acuity was reduced to 20/200 or less by providing several occlusion membranes, and results were compared with customary full correction for distance. The best improvement of their vision by this system was achieved when the dioptric power of the spectacle was between +11.0 D and +13.75 D. This system was then applied to 78 eyes (61 patients) with visual acuity of 20/100 or less. Subjective improvement of vision was found in 55% of those patients' eyes. Eight patients out of 26 patients whose better eye acuity was 20/100 or less wanted to use this system and received prescription to result in the visual improvement, as evidenced by their continued use. This system can provide aid for low vision correction for distance. PMID- 1442362 TI - [Auto recording system for the Goldmann perimeter]. AB - In order to develop a method for converting the Goldmann perimeter data directly for computer storage and evaluation, a recording instrument was designed as a modification of the Goldmann perimeter. By installing the two potentiometers on the pantographic arm and electrical switches, the position of the test target and the setting of the four levers which defines the size and the brightness of the test target were transferred directly to the computer. Accuracy of this recording system is better than 1.3 degree over the entire surface of the chart. This system will make it possible to easily follow changes in the visual fields of the same patient, i.e. shape change, numerical value. PMID- 1442363 TI - [A case of metastatic carcinoma to the retina]. AB - The authors report a case of metastatic carcinoma to the retina. The patient was a 61-year-old man who had an operation for a well-differentiated adenocarcinoma of the rectum. Ophthalmoscopic examination disclosed a single, white, elevated mass lesion surrounded by serous retinal detachment located in the upper part of the macula of the right eye. A few retinal hemorrhages existed around the lesion. Fluorescein angiography revealed partially obscured retinal vessels due to compression by the tumor and arteriovenous anastomosis. Postmortem pathologic examination confirmed metastases to the brain, lung and retina. Microscopic examination showed a retinal lesion and tumor cells in the right eye. Tumor cells, similar to the carcinoma of the rectum, were present only in the neurosensory retina and did not invade the pigmented epithelium or choroid. PMID- 1442364 TI - [Ocular manifestations in a case of infantile cystinosis]. AB - A case of infantile cystinosis was reported. The diagnosis of cystinosis was made by the renal Fanconi syndrome and the ocular findings. The patient showed typical corneal and fundus changes associated with cystinosis. Corneal crystals and fundus pigmentary change were found early in life. The deposition of corneal crystals increased in the course of the disease, especially in the nasal and the temporal sides close to the limbus. By specular microscopy, the corneal crystals were needle-shaped and were larger and more numerous in the superficial layer of the stroma. The same shape of crystals ere found in the corneal endothelium, and the size of endothelial cells was markedly increased. There were also small crystals on the surface of the iris. The entire fundus showed a mottled appearance characterized by mixture of fine granular pigmentation and depigmentation associated with patchy depigmentation in the periphery. On the anterior surface of the retina, a glistening crystal appeared. As the crystal deposition in ocular tissues increases, even after successful peritoneal dialysis, eventual impairment of visual function may be expected. PMID- 1442365 TI - Effects on testosterone, LH and cortisol concentrations, and on testicular ultrasonographic appearance of induced testicular degeneration in bulls. AB - It is well known that heat stress has a detrimental effect on testicular functions. In addition to the alteration of semen quality and testicular damage, reproductive hormone secretion can be altered. The objective of this study was to describe changes in plasma concentrations of testosterone, LH and cortisol, as well as in testicular ultrasonographic appearance after induced testicular degeneration. Four Swedish Red and White bulls, aged 3 years, were used. They were fed according to Swedish standards. The scrotum was covered with an insulation device during 96 h. Semen was collected weekly 3 times before and up to 4 months after insulation. Testicular ultrasonography and clinical genital examination were performed with the same intervals. Heparinized blood samples were taken from the jugular vein at 2 h interval during 24 h every 2 weeks during the study. Blood samples were tested for the content of testosterone, LH and cortisol. Data were analysed, using one way analysis of variance of seminal data, clinical examination data as well as 24 h hormonal output data as percentage of mean individual pretreatment values. The use of a 5 MHz B-mode ultrasound unit did not contribute with an objective estimation of the degree of testicular degeneration. In 3 of the bulls testosterone levels had a tendency to decrease and LH to increase during the time of severe degeneration, whereas an opposite trend was seen during the regenerative phase, changes becoming significant 15 weeks after scrotal insulation. Variation between animals was big. Cortisol levels had a decreasing trend, changes being significant only in individual bulls at 10 and 15 weeks after scrotal insulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442366 TI - Colostral growth factors. Possible role in bovine udder epithelial cell regeneration. AB - Growth of the secretory epithelium during prepartum time, and for a short period after calving, is under hormonal control by estrogen, progesterone and prolactin. The mechanism(s) by which these hormones act is not known but colostrum and milk have been shown to contain different growth promoting substances. In an attempt to unravel these relationships the effect of bovine colostrum on cellular proliferation in vitro have been characterized. Colostral thermostable factors not present in milk nor associated with fat, potently induce the proliferation associated enzyme, ornithine decarboxylase, in fibroblast cell lines. However, mammary epithelial cells appear to proliferate in response to different colostral heat sensitive factor(s) that await further characterization. PMID- 1442367 TI - Mycoplasma hyosynoviae in joints with arthritis in abattoir baconers. AB - The occurrence of Mycoplasma hyosynoviae in synovial fluid of baconers with chronic arthritis was studied at an abattoir. Cultural examination of synovial fluid samples from diseased tarsal joints of 50 animals from 42 herds yielded M. hyosynoviae in 10 cases from 8 herds. Streptococci were found in 6 cases from 6 other herds. M. hyosynoviae antigen was found in 1 of 47 of the samples, and antibody to the mycoplasma was found in 14 of 40 of the samples by ELISA test. The presence of M. hyosynoviae in a joint was usually accompanied by the corresponding antibody. In joints with streptococcal infection antibody to M. hyosynoviae could not be found. PMID- 1442368 TI - Critical difference of some bovine haematological parameters. AB - The purpose of the present study was to calculate the critical difference between 2 analytical results for the red blood cell count (RBC), the white blood cell count (WBC), the haemoglobin concentration (Hb), and the haematocrit (PCV) in blood from Red Danish Dairy cows. The critical difference can help to judge whether the difference between 2 consecutive analytical results from the same animal may be safely ascribed to natural variation or not. To calculate the critical differences, blood samples from 20 clinically healthy lactating cows were collected once daily for 5 consecutive days. The total variance of the analytical results was divided into the component of variance between cows (S2Inter), the component of variance for days within cows (S2Intra), and the component of variance for measurements (S2Anal) using nested analysis of variance. The critical difference was then calculated from S2Intra and S2Anal as 0.61 x 10(12)/l for RBC, 2.2 x 10(9)/l for WBC, 0.79 mmol/l for Hb, and 0.07 for PCV. The critical differences may be used as guidelines to indicate potentially important changes in the parameters. However, the analytical results should not be assessed by the critical differences alone, but should also be compared to the corresponding reference intervals. PMID- 1442369 TI - The use of isophane insulin for the control of diabetes mellitus in dogs. AB - For this study 54 dogs with diabetes mellitus verified by anamnesis, clinical examinations and laboratory analyses were selected in 13 Danish and Swedish small animal clinics. After instruction the owners gave isophane insulin ("Insulin Protaphan Human") injections to the dogs morning and evening followed by a commercial or homemade meal rich in fibers. The veterinarians examined the treated dogs 5 times or more in the 90 day treatment period, preferably in the morning before injection and meal. In all 54 dogs the clinical symptoms disappeared a few days after isophane insulin injections, and 54% of the dogs were clinically healthy within 8 days. Within a month 96% of the dogs were normalized after therapy. Simultaneously the blood glucose levels were normalized in 64% of the dogs within 14 days and in further 21% within 30 days. The urine glucose levels were normalized in 64% of the dogs within 14 days and for further 19% within 30 days. At the end of the study 48 out of the 54 diabetic dogs were clinically healthy, alert and free from symptoms of diabetes. The average dose of isophane insulin was for greater dogs 0.44 units per kg bw twice a day, for small dogs 0.79. Six dogs had been destroyed in the trial period for various reasons. One owner had injection troubles. Another owner was hospitalized and had to get rid of the dog. One dog developed advanced breast cancer, 1 went fierce and 2 developed cataracts. Four dogs had by 1 or 2 occasions shown hypoglycemic symptoms, which quickly disappeared after appropriate adjustments of insulin dosing, feeding schedule and exercise programme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442370 TI - Experimental infections with Cooperia oncophora in calves. A study with two different larval dose levels and dosing regimens. AB - The effect of different larval dose level and dosing regimens on the course of Cooperia oncophora infection in calves was studied. Four groups each of 4 calves were experimentally infected either with 50,000 or 200,000 C. oncophora larvae (L3) given either as single infections or as daily trickle infections. An additional group of calves remained as uninfected controls. The animals were necropsied on week 4 after infection. Mild to moderate clinical signs of parasitic gastroenteritis developed among calves given high doses of larvae, but liveweight gains were not significantly different from those of the uninfected controls. Serum pepsinogen levels of dosed animals were within normal ranges but rose slightly, and on day 14 p.i. they differed significantly from those of the controls. On that occasion, the levels of serum pepsinogen in the trickle infected groups significantly exhibited the levels of the single infected groups. Hypoalbuminaemia was not a feature on any occasion. The various groups did not differ significantly with regard to total worm counts and adult worm counts, but the groups receiving high larval dose harboured significantly more fourth stage larvae than the group receiving low doses of larvae, both in terms of absolute counts and in terms of percentages of total worm burdens. Within the same dose level, there was a tendency of a more even distribution of worms along the small intestine when the infections was given as a single infection compared with a trickle infection. The results indicate that C. oncophora larval dose and dosing regimens may influence the pathogenic effects and to some extent the distribution of the parasite in the small intestine. PMID- 1442371 TI - Coculture of bovine demiembryos prior to freezing. AB - Pregnancy rates after transfer of frozen/thawed bisected embryos, demiembryos, have until now been very low. In the present study it was attempted to improve the freezability rate of demiembryos by culturing them on a monolayer of bovine oviduct epithelial cells (BOEC) prior to freezing. The cultured frozen/thawed demiembryos showed a lower developmental rate than intact embryos. The pregnancy rate (23%) following transfer was not different from the pregnancy rate after transfer of unfrozen demiembryos (26%). The calving rate (4%), however, was significantly lower than the calving rate after transfer of fresh demiembryos (23%). Although the overall pregnancy rate achieved in this study was low, it can be concluded that a co-culture period upon BOEC prior to freezing does not improve the viability of frozen demiembryos. PMID- 1442372 TI - Effect of flunixin meglumine on the endocrine control of luteolysis in the porcine estrous cycle. PMID- 1442373 TI - Neonatal changes in plasma erythropoietin in fast growing pigs. PMID- 1442374 TI - George W. Holmes Lecture. Deep venous thrombosis and pulmonary embolism: correlative evaluation and therapeutic implications. AB - Deep venous thrombosis and pulmonary embolism are significant causes of morbidity and mortality in the United States; estimates range from 120,000 to 150,000 deaths annually. Although usually symptomatic, deep venous thrombosis can be clinically occult, in part due to incomplete obstruction or in part related to duplication, triplication, and fenestration anomalies, primarily of the superficial femoral or popliteal vein. Additionally, pulmonary emboli caused by deep venous thrombosis may be clinically silent. Because of therapeutic implications, especially indications for insertion of inferior vena caval filters, comprehensive assessments of both the disease process (i.e., deep venous thrombosis) and the complication (i.e., pulmonary emboli) are important. Thus, when a pulmonary embolus is the presenting process, correlative assessment of deep venous thrombosis, even in the absence of symptoms or signs in the lower extremity, may be of therapeutic significance. Conversely, when deep venous thrombosis of the lower extremities involving the popliteal or superficial femoral vein is the presenting process, correlative assessment of the pulmonary circulation, even when no pulmonary symptoms or signs are present, may be of therapeutic significance. Relative to the diagnosis of pulmonary embolism, the roles of assays of D-dimer, ventilation-perfusion lung scans, and segmental occlusion studies of the pulmonary circulation are discussed. Finally, the indications for insertion of inferior vena caval filters above the renal veins are presented and examples are shown. PMID- 1442375 TI - Radiation effects on the lung: clinical features, pathology, and imaging findings. PMID- 1442376 TI - Epilepsy: the role of MR imaging. AB - MR is the imaging technique of choice when examining a patient who is having seizures. Detection, localization, and differentiation of structural epileptogenic abnormalities are much better with MR imaging than with CT. MR imaging has a high success rate in identifying hippocampal sclerosis, a common cause of surgically treatable temporal lobe epilepsy. The affected hippocampus is atrophic and hyperintense on long TR images. Functional imaging with single photon emission computed tomography and positron emission tomography is complementary to MR imaging but is not as widely available. In summary, MR imaging has dramatically changed the workup of epilepsy, especially for the patient with medically uncontrollable seizures. As surgical treatment of epilepsy becomes more available, the need for preoperative evaluation with MR imaging will increase. PMID- 1442377 TI - CT appearance of pulmonary tuberculosis in diabetic and immunocompromised patients: comparison with patients who had no underlying disease. AB - OBJECTIVE: It has been stated, but not adequately assessed, that pulmonary tuberculosis in diabetic or immunocompromised patients often has an atypical pattern and distribution. To evaluate the CT features of pulmonary tuberculosis in diabetic or immunocompromised patients compared with patients without underlying disease, we performed this retrospective study. MATERIALS AND METHODS: We reviewed conventional CT scans (n = 100) and high-resolution CT scans (n = 16) of the chest in 110 adult patients with active postprimary tuberculosis. Seventy one patients had no underlying disease, 31 had diabetes mellitus, and eight were immunocompromised. RESULTS: In patients who had no underlying disease, 44 had nodular opacities, 11 had consolidation, and 13 had consolidation with associated loss of volume. Characteristic features of tuberculosis in this group of patients included segmental distribution (97%), satellite lesions (93%), single cavity within any given lesion (95%), and tendency toward architectural distortion and loss of volume. In diabetic and immunocompromised patients, 15 had nodular opacities, seven had consolidation, and 15 had consolidation with associated loss of volume. Diabetic and immunocompromised patients had a high prevalence of nonsegmental distribution (30%) and multiple small cavities within any given lesion (44%). Unusual localization of tuberculosis, including disease confined to the basal segments of the lower lobes, anterior segment of the upper lobes, or right middle lobe, occurred equally in both groups (17% and 18%). CONCLUSION: We conclude that diabetic and immunocompromised patients have a higher prevalence of multiple cavities within any given lesion (p < .01) and of nonsegmental distribution (p < .01) than do patients without underlying disease. PMID- 1442378 TI - CT of fatty thoracic masses. PMID- 1442379 TI - A modified technique for breast compression during needle localization. PMID- 1442380 TI - Imaging of patients with potentially resectable hepatic neoplasms. PMID- 1442381 TI - Nominal dysphasia. PMID- 1442382 TI - Reversed or absent hepatic arterial diastolic flow in liver transplants shown by duplex sonography: a poor predictor of subsequent hepatic artery thrombosis. AB - OBJECTIVE: We studied the value of absent or reversed diastolic flow in the hepatic artery, shown by duplex sonography of recently transplanted livers, in predicting subsequent hepatic artery thrombosis. MATERIALS AND METHODS: We retrospectively reviewed the records of liver transplantations performed in adults during a 3-year period at our institution. Duplex Doppler studies were done within 24 hr after transplantation and subsequently reviewed. The clinical course of all patients with absent or reversed diastolic flow in the hepatic artery immediately after transplantation was evaluated. RESULTS: Of the 160 liver transplants included in this study, 30 had aberrant diastolic flow in the hepatic artery immediately after transplantation. Twenty had reversed flow, and 10 showed no flow in diastole. In this group of 30 transplants, complications developed in six; two were vascular in origin. One of these complications was thrombosis of the hepatic artery 12 months after transplantation. This 3% thrombosis rate is similar to the 4.6% thrombosis rate of the 130 patients who had antegrade diastolic flow in the hepatic artery immediately after transplantation. CONCLUSION: Reversed or absent diastolic flow in the hepatic artery of a recently transplanted liver has no correlation with subsequent hepatic artery thrombosis. PMID- 1442383 TI - Filling defects in the pancreatic duct on endoscopic retrograde pancreatography. AB - Filling defects in the pancreatic duct are a frequent finding during endoscopic retrograde pancreatography (ERP) and have a variety of causes. Some filling defects may be artifactual or related to technical factors and, once their origin is recognized, can be disregarded. Others may be due to acute changes of pancreatitis and should prompt more careful injection of contrast material into the duct. Intraluminal masses may represent calculi or a neoplasm, either of which may require surgery or endoscopic intervention. The exact nature of these filling defects may not be apparent on radiographs, and other studies may be needed. This article reviews our approach to the evaluation of filling defects in the pancreatic duct. PMID- 1442384 TI - Spiral CT of the pancreas with multiplanar display. AB - This essay illustrates the findings obtained with spiral CT imaging in pancreatic disease. Features of spiral CT--fast scanning, dynamic injection of contrast material allowing optimal vessel opacification, and supplemental multiplanar imaging--promise to provide increased accuracy in the diagnosis and staging of pancreatic disease. With further development of continuous (spiral/helical) scanning technology, this technology should expand to cover a wider range of applications. PMID- 1442385 TI - Rupture of the bowel after blunt abdominal trauma: diagnosis with CT. AB - OBJECTIVE: The accuracy of CT in the detection of injuries of the solid viscera after blunt trauma is well established, but the value of CT in diagnosing bowel rupture resulting from blunt trauma is controversial. This study was conducted to determine the sensitivity of CT in diagnosing posttraumatic bowel rupture. SUBJECTS AND METHODS: During a 51-month period, 17 preoperative CT scans were obtained in 16 patients who subsequently had bowel ruptures verified surgically. Both preoperative (prospective) and retrospective CT findings were analyzed in these patients. Retrospective interpretation was made by consensus of two radiologists. RESULTS: Surgically confirmed bowel ruptures occurred in the duodenum (five), ileum (four), jejunum (four), colon (four), and stomach (two). CT findings considered diagnostic of bowel perforation were detected prospectively on 10 (59%) of 17 scans; these included pneumoperitoneum without prior peritoneal lavage (six), mesenteric, intramural, or retroperitoneal free air (six), or direct visualization of discontinuity of the bowel wall or extravasation of luminal contents (four). Prospective CT findings considered suggestive of bowel rupture were present on five (29%) of the 17 scans; these included intraperitoneal fluid of unknown source (three), thickened (> 4-5 mm) bowel wall (two), gross anterior pararenal fluid without a recognized source (one), and a mesenteric-bowel wall hematoma (one). On two of 17 scans, findings were seen in retrospect only; these included free intraperitoneal blood without a source (findings on a second CT scan were diagnostic) and pneumoperitoneum. CT findings diagnostic or suggestive of bowel injury were detected prospectively on 15 (88%) of 17 scans and were noted in all retrospectively. CONCLUSION: CT is sensitive for the diagnosis of bowel rupture resulting from blunt trauma, but careful inspection and technique are required to detect often subtle findings. PMID- 1442386 TI - Replacement of nasogastric suction by retrograde jejunogastric tube drainage in the management of esophagogastric complications. PMID- 1442387 TI - Arteriovenous malformation of the small bowel diagnosed with enteroclysis. PMID- 1442388 TI - Transcatheter placement of a metallic stent for treatment of an occluded H-graft portacaval shunt. PMID- 1442389 TI - The natural history of renal lesions in von Hippel-Lindau disease: a serial CT study in 28 patients. AB - OBJECTIVE: Von Hippel-Lindau disease is a multisystem disorder predisposing to renal cysts and cancer. The growth and development of these renal lesions have not been documented previously. We reviewed serial CT scans to determine the rates and patterns of growth of renal lesions associated with von Hippel-Lindau disease. SUBJECTS AND METHODS: Twenty-eight patients with von Hippel-Lindau disease and renal involvement, including the spectrum from simple cysts to solid masses, had follow-up examinations for at least 1 year (mean, 2.4 years; range, 1 12 years) with serial contrast-enhanced abdominal CT. Renal lesions were measured and characterized. Surgical correlation was available in 12 patients. RESULTS: Two hundred twenty-eight lesions (eight lesions per patient) were detected. On the basis of their CT appearance, 168 lesions (74%) were classified as cysts, 18 (8%) as cysts with solid components, and 42 (18%) as solid masses. Among 12 patients with pathologic confirmation, the solid components of cystic lesions and solid lesions almost always contained renal carcinoma. The majority of cysts remained the same size (71%) or enlarged (20%); 9% became smaller or entirely involuted during the follow-up period. Although it is generally presumed that renal cysts are precursors to cancers, the transformation of a simple cyst to a solid lesion was observed in only two patients. Among the 42 solid lesions, all but two enlarged with time, with a mean doubling time of 10 months. CONCLUSION: The renal lesions associated with von Hippel-Lindau disease exhibited wide differences in growth. The majority of renal cysts grew slowly but some involuted. Transition to solid renal cancer was rare among cysts. Complex cystic and solid lesions contained neoplastic tissue that uniformly enlarged. These data may be used to help predict the progression of renal lesions in von Hippel-Lindau disease. PMID- 1442390 TI - Cystic renal cell carcinoma: CT findings simulating a benign hyperdense cyst. PMID- 1442391 TI - Sonographic findings after surgical ablation of the endometrium. AB - OBJECTIVE: Endometrial ablation is a new surgical technique that is an alternative to hysterectomy in women with dysfunctional uterine bleeding. The endometrium is either coagulated or resected in an attempt to render the patient amenorrheic. Because of the newness of the procedure, no report of radiologic findings after endometrial ablation has been published. Accordingly, the sonographic appearance of the uterus after endometrial ablation is described. MATERIALS AND METHODS: Using transvaginal sonography, we examined a select group of 16 women, seven of whom were symptomatic after endometrial ablation. All patients had a preoperative diagnosis of menorrhagia not responsive to conventional hormonal therapy and no evidence of cancer. RESULTS: In the seven symptomatic patients, sonography showed that postoperatively two had hematometra, one had a nonviable intrauterine pregnancy, and four had residual islands of functioning endometrial tissue alone or in combination with hematometra. In nine asymptomatic patients, postoperative sonography showed seven had normal findings except for leiomyomata and two had residual islands of functioning endometrial tissue. CONCLUSION: Sonographic examination of the uterus after endometrial ablation provides a method for evaluating symptomatic patients and for identifying any remaining endometrium that could later become symptomatic. PMID- 1442392 TI - Early radiology at the University of Texas Medical Branch, Galveston. PMID- 1442393 TI - MR imaging of pelvic masses in women: contrast-enhanced vs unenhanced images. AB - OBJECTIVE: We compared the value of contrast-enhanced MR images with that of T2 weighted MR images in the diagnosis and staging of pelvic masses in women. MATERIALS AND METHODS: The findings on preoperative MR studies of 97 patients with a total of 124 surgically proved lesions were retrospectively analyzed. Unenhanced T1- and T2-weighted spin-echo images were compared with contrast enhanced T1-weighted images. The final diagnosis included benign (36 patients), borderline (six patients), and malignant (15 patients) ovarian masses, fallopian tube masses (15 patients), endometrial tumors (seven patients), cervical carcinomas (32 patients), subserous leiomyomas (11 patients), and two masses of extragenital origin. RESULTS: In the depiction of pelvic lesions, the sensitivity of contrast-enhanced MR imaging (96%) was equal to that of unenhanced T2-weighted imaging (97%). Contrast-enhanced images were useful in the definition of intratumoral architecture and tumor borders of 72 adnexal masses, resulting in better determination of malignancy (accuracy, 95%) than on T2-weighted images (85%). Size of viable tumor, differentiation of tumor from retained fluid, and depth of myometrial invasion of six endometrial carcinomas were most reliably shown on contrast-enhanced images. In the evaluation of cervical carcinoma, overall staging accuracy of contrast-enhanced imaging (80%) was slightly inferior to that of T2-weighted imaging (83%). However, contrast-enhanced images improved assessment of parametrial and organ invasion in seven cases in which findings on T2-weighted MR images were equivocal. Administration of contrast material was not helpful in the evaluation of subserous leiomyomas or masses of extragenital origin. CONCLUSIONS: The findings suggest that when results of unenhanced T1- and T2-weighted MR imaging of pelvic masses are equivocal, contrast-enhanced MR images should be used as supportive and complementary pulse sequences to (1) improve definition of intratumoral architecture and prediction of malignancy in adnexal tumors, (2) stage endometrial carcinoma, and (3) determine tumor extension in cervical carcinoma. PMID- 1442394 TI - Adnexal torsion: diagnosis by using Doppler sonography. PMID- 1442395 TI - Polyethylene osteolysis. PMID- 1442396 TI - Detection of acute avascular necrosis of the femoral head in dogs: dynamic contrast-enhanced MR imaging vs spin-echo and STIR sequences. AB - OBJECTIVE: Spin-echo MR imaging has been shown to be highly sensitive in the detection of avascular necrosis. Very early avascular necrosis can, however, appear normal on MR images. We compared dynamic contrast-enhanced MR imaging with conventional spin-echo and short Tl inversion-recovery (STIR) sequences for detecting acute osteonecrosis in an animal model. MATERIALS AND METHODS: Avascular necrosis was induced unilaterally in the femoral heads of five dogs that were imaged with a 1.5-T system within 3 hr of devascularization. After standard T1-weighted, T2-weighted, and STIR images, gradient-recalled echo images, 28/5 (TR/TE) with a 45 degrees flip angle, were obtained at 6-sec intervals for 90 sec synchronous with the IV administration of 0.2 mmol of gadoteridol per kilogram of body weight at a rate of 2 ml/sec via an automated injector. Two animals were reimaged after 7 days. RESULTS: Spin-echo and STIR images did not show any acute changes in the ischemic femoral heads. In contrast, significant differences were present in the enhancement profiles of the marrow spaces in the normal and ischemic femoral heads (p = .005). Normal marrow was characterized by rapid enhancement, with an average signal intensity increase of 83% peaking at 36 sec; no measurable enhancement was seen in the marrow of the ischemic femoral head. Spin-echo images, obtained 7 days after devascularization (n = 2), showed changes characteristic of avascular necrosis. Dynamic contrast enhanced MR images showed persistent lack of enhancement in the avascular marrow of the ischemic femoral head. A junctional zone, characterized by rapid contrast enhancement in excess of 120% without early washout, was identified at the interface between normal and avascular marrow. CONCLUSION: In this experimental model, dynamic contrast-enhanced MR imaging proved significantly more sensitive than conventional spin-echo and STIR imaging in the detection of acute avascular necrosis. PMID- 1442397 TI - CT findings in a case of exuberant cervical fibrosclerosis. PMID- 1442398 TI - Acute appendicitis in children: value of sonography in detecting perforation. AB - OBJECTIVE: We determined the sonographic features of perforating appendicitis in children in order to determine the best criteria for establishing the diagnosis. MATERIALS AND METHODS: Sonograms of the right lower quadrants of 71 children with proved appendicitis were reviewed to determine the value of sonography in distinguishing between nonperforating and perforating appendicitis. The sonographic signs evaluated included the presence or absence of an appendix, an echogenic submucosal layer, increased periappendiceal echogenicity, free or loculated periappendiceal or pelvic fluid collections, and appendicoliths. The sonographic findings were correlated with the surgical and pathologic findings. RESULTS: Forty-five patients had nonperforating appendicitis, and 26 had perforating appendicitis. A sonographically visible appendix was present in all patients with nonperforating appendicitis and in 10 (38%) of 26 patients with perforation. An echogenic submucosa was noted in 27 (60%) of 45 patients with uncomplicated appendicitis but in only three (30%) of 10 patients with a visible appendix and perforating appendicitis (p < .05). In 19 of 26 patients with perforating appendicitis, sonography showed loculated periappendiceal or pelvic fluid collections; no patient with nonperforating appendicitis had a loculated fluid collection (p < .05). No statistically significant association was found between the presence or absence of perforation and free pelvic fluid, prominent periappendiceal fat, or an appendicolith. CONCLUSION: Our results indicate that sonography can be helpful in the diagnosis of perforating appendicitis. The best predictors of perforation are absence of the echogenic submucosal layer and the presence of a loculated fluid collection. PMID- 1442399 TI - Congenital subglottic hemangioma: frequency of symmetric subglottic narrowing on frontal radiographs of the neck. AB - OBJECTIVE: This study was undertaken to determine how often symmetric subglottic airway narrowing is present in cases of infantile subglottic stenosis and to determine if the radiographic finding has any association with the anatomic location of the hemangioma. MATERIALS AND METHODS: All cases (n = 12) of endoscopically proved subglottic hemangioma from 1976 to 1991 were collected from the records at Children's Hospital of Michigan. In 10 cases, high-kilovoltage magnification studies or frontal radiographs of the neck were available for review by two observers who classified the subglottic narrowing as either symmetric or asymmetric. The radiographic findings in these 10 cases were then compared with the location and extent of the lesion as described endoscopically. RESULTS: In 50% of cases (n = 5), narrowing of the subglottic airway was symmetric. In four of these the hemangioma was either situated on the posterior wall or was circumferential, and in the remaining one an associated marked fibrotic reaction to a lateral wall lesion was present. All other lesions were on the lateral wall, and asymmetric subglottic airway narrowing was consistently shown on radiographs. CONCLUSION: Our results show that subglottic hemangioma often manifests as a symmetric subglottic airway narrowing and that the anatomic location of the hemangioma appears to be associated with the appearance on radiographs. PMID- 1442400 TI - Atresia of the colon in neonates: radiographic findings. PMID- 1442401 TI - Transjugular intrahepatic portosystemic shunt in a child with cystic fibrosis. PMID- 1442402 TI - Determination of magnetization transfer contrast in tissue: an MR imaging study of brain tumors. AB - OBJECTIVE: In this study, the magnetization transfer contrast (MTC) on MR images of several brain tumors and the correlation between MTC and tumors' histologic features were investigated. MTC depends on the extent of magnetization transfer, or cross-relaxation, from tissue water protons to macromolecular protons. On the basis of the known increase of the cross-relaxation rate with increasing molecular weight of protein in protein solutions, the hypothesis that changes in MTC correlate directly with the macromolecular composition of various tumors was tested. SUBJECTS AND METHODS: Preoperative MR images were obtained with a 0.1-T MR system in 40 patients with brain tumors. MTC was correlated with the histologic features and the dry weight of the tumors. The tumors studied included astrocytomas (10), acoustic schwannomas (three), meningiomas (12), pituitary adenomas (10), craniopharyngiomas (two), and hemangioblastomas (three). RESULTS: MTC was 0.43 in normal white matter and 0.42 in normal gray matter, and varied from 0.11 to 0.37 in the tumors. The mean MTC in astrocytomas (0.21 +/- 0.09) was smaller than the mean MTC in the gray matter (p = .0001) or in the other solid tumors (0.34 +/- 0.07 to 0.37 +/- 0.09, p < .002). MTC was larger in high-grade than in low-grade astrocytomas (0.28 +/- 0.05 vs 0.14 +/- 0.04, p = .0005). In meningiomas, MTC correlated with the collagen content of the tumor tissue (r = .95, p = .01). The differences in contents of solids between the solid tumor groups were not significant (p > or = .1, NS). CONCLUSION: When the previously demonstrated correlations between solid content and 1/T1 of the types of tumors studied are taken into consideration, the present results suggest a larger relative contribution from hydrodynamic vs cross-relaxation effects in astrocytomas than in benign tumors or in gray matter. The twofold difference in MTC between low- and high-grade astrocytomas probably reflects the amount of nuclear material in the tumor cells. Collagen content determined the differences in MTC among meningiomas. These results indicate that the major determinant of differences in MTC within these tumor groups is the high-molecular-weight tissue macromolecules, suggesting higher specificity for MTC than for T1 in discriminating between tissues on MR images. PMID- 1442403 TI - Pleomorphic xanthoastrocytoma of the brain: MR findings in six patients. AB - OBJECTIVE: Pleomorphic xanthoastrocytoma is a rare, usually benign brain tumor. This pleomorphic supratentorial tumor involves the leptomeninges and superficial cortex in young patients with seizures. The MR imaging features of this distinct tumor have not been reported. We describe the MR imaging findings in six patients with pathologically proved pleomorphic xanthoastrocytoma. MATERIALS AND METHODS: We retrospectively reviewed the MR images of six patients with pathologically proved pleomorphic xanthoastrocytoma. MR images were reviewed by two neuroradiologists. The pathologic slides of the tumors were reviewed by two neuropathologists. We also analyzed the patients' clinical features. RESULTS: Most of the tumors were cortical based and isointense with gray matter on T1 weighted images and mildly hyperintense on T2-weighted images. All the masses enhanced with contrast material. Cystic components and gyriform and leptomeningeal enhancement were seen occasionally. The tumors occurred in the temporal lobes in four of the six patients. Three patients had seizures, and the other three had headaches. CONCLUSION: Pleomorphic xanthoastrocytoma is a rare, usually benign, cortical-based mass that often enhances intensely with contrast material. The most common location is in the temporal lobes. Seizures and headaches are common clinical features. Familiarity with this lesion is important in the differential diagnosis of enhancing cortical-based masses. PMID- 1442404 TI - Calcification of the trochlear apparatus of the orbit: CT appearance and association with diabetes and age. AB - OBJECTIVE: Calcification can sometimes be observed on CT scans in the region of the trochlear apparatus of the orbit, the cartilaginous structure through which the superior oblique tendon and its sheath pass. We evaluated associations of trochlear calcifications with age and diabetes. MATERIALS AND METHODS: We retrospectively reviewed CT scans of the orbit in 159 patients to identify the presence of trochlear calcifications. The presence or absence of diabetes, duration of diabetes, type of therapy, and presence or absence of neuropathy were determined from medical charts of 139 patients. We calculated the odds ratio of detecting a trochlear calcification and used logistic regression to evaluate the associations of age, sex, and diabetes with trochlear calcification. RESULTS: Trochlear calcifications were present in seven of the 24 diabetic patients and in 10 of the 115 nondiabetic patients. The odds ratio for detecting trochlear calcifications in diabetic vs nondiabetic patients was 4.3 (p < .01). Logistic regression showed univariate associations with trochlear calcification for both increasing age (p < .001) and diabetes mellitus (p < .01). The effect of diabetes on the prevalence of trochlear calcifications was seen predominantly in those less than 40 years old (odds ratio = 24.0, p = .014). Sex, duration of diabetes, insulin dependence, and neuropathy were not significantly associated with an increase in trochlear calcifications. CONCLUSION: The results show that a trochlear calcification seen on CT is a benign condition that may serve as a marker for diabetes in young patients. Trochlear calcifications are observed frequently (25-30%) in persons more than 50 years old. When it is present in patients younger than 40 years, it is strongly associated with diabetes. PMID- 1442405 TI - Do abnormalities of the frontonasal duct cause frontal sinusitis? A CT study in 198 patients. AB - OBJECTIVE: The purpose of the study was to determine the correlation between frontonasal duct abnormalities (narrowing or obstruction caused by hypertrophic mucosa) and frontal sinusitis. This study was based on the hypothesis that abnormalities of the frontonasal duct cause frontal sinusitis by impairing normal drainage of the sinus. MATERIALS AND METHODS: CT studies of 198 consecutive patients with clinical diagnoses of chronic sinusitis were reviewed retrospectively. Criteria for inclusion were (1) no history of sinus surgery or facial trauma and (2) absence of polyps at rhinoscopy. As 37 frontal sinuses were undeveloped, a total of 359 sinuses were evaluated. CT scans were obtained in oblique axial and coronal planes. The following CT features were assessed: (1) the frequency of detection of the frontonasal duct, (2) the appearance of the frontonasal duct: normal vs abnormal (narrowed or obstructed), and (3) the correlations between abnormalities of the frontonasal duct and frontal sinusitis. RESULTS: The frontonasal duct was detected in all 359 cases, either in both CT planes (81%) or only in the axial oblique plane (19%). In 267 (74%) of 359 cases, the duct appeared normal; among these, isolated frontal sinusitis was detected in five cases (2%). In 92 (26%) of 359 cases, the duct was abnormal; it was narrowed in 18 cases (5%) and obstructed in 74 cases (21%). Frontal sinusitis was noted in 78 (85%) of the 92 cases of frontonasal duct abnormalities. The sensitivity and specificity of the correlations between frontonasal duct abnormalities and frontal sinusitis were 98% and 85%, respectively. CONCLUSION: Because our results show a strong correlation between abnormalities of the frontonasal duct and frontal sinusitis, it seems highly probable that abnormalities of the frontonasal duct cause frontal sinusitis. PMID- 1442406 TI - Venous angioma of the brain: history, significance, and imaging findings. PMID- 1442407 TI - Normal anatomy of the hippocampus and adjacent temporal lobe: high-resolution fast spin-echo MR images in volunteers correlated with cadaveric histologic sections. AB - This essay illustrates the appearances of sections of the normal hippocampus and adjacent temporal lobe on high-resolution heavily T2-weighted fast spin-echo MR images and correlates them with histologic sections. We found that this MR examination showed the detailed anatomy of the normal hippocampus in a much shorter time than is possible with conventional spin-echo techniques. The information provided in this essay can be used as a baseline for distinguishing between normal and abnormal hippocampi in a variety of disease states. PMID- 1442408 TI - MR myelography using heavily T2-weighted fast spin-echo pulse sequences with fat presaturation. AB - A new method for generating myelogramlike images of the thecal sac by MR imaging is presented. The method is based on suppressing background signal by using heavily T2-weighted fast spin-echo pulse sequences and obliterating fat signal by presaturation. The resulting slices are then projected into a composite image using a standard maximum intensity projection (MIP) algorithm. The technique is implemented with commercially available hardware and software and yields reproducible high-quality images of the lumbar thecal sac, which show excellent definition of the thecal margins, nerve roots, and nerve root sheaths. This method could replace conventional lumbar myelography and postmyelographic CT studies. PMID- 1442409 TI - Assessment of a neuroradiology picture archiving and communication system in clinical practice. AB - The goal of this study was to determine if our neuroradiology picture archiving and communication system (PACS) is capable of improving the efficiency and function of the management and review of neuroradiologic images. A neuroradiology PACS module developed in our department was evaluated in the clinical environment from February 1990 through July 1991. The overall evaluation focused on three aspects: (1) image delivery performance, (2) system availability, and (3) user acceptance. Image delivery performance was evaluated by analyzing the time spent on each modularized task with both the film-based system and the PACS system. The system availability was examined by observing the downtime occurrence and uptime probability of individual hardware components in the PACS module. User acceptance was evaluated through a survey done with the display workstation. Under regular operating conditions, the PACS outperforms the current film-based operation. The overall PACS module availability is more than 92%, with the display workstation available more than 99% of the time. The overall user acceptance of the system is 3.4 on a four-point ranking scale. This study has demonstrated the full functionality and clinical usefulness of our neuroradiology PACS. On the basis of the results of this study, a large-scale PACS has been designed and implemented in our department. PMID- 1442410 TI - Integration of a personal computer workstation and radiology information system for obstetric sonography. AB - A personal computer workstation has been developed for storage and analysis of obstetric sonographic examinations. The workstation also serves as an interactive data terminal for our radiology information system. A data-base management program locally stores quantitative and descriptive sonographic results. Algorithms are used to analyze growth parameters over serial examinations, plot growth curves, generate a radiologic report, and provide instantaneous diagnostic assistance and suggestions. A bibliographic data-base system containing more than 3000 references (with abstracts) in the obstetric sonographic literature is integrated with the software's analytical functions. A telecommunications software module performs dialogues, such as immediate automatic transcription of the sonographic report, with the radiology information system. An examination summary form, growth curves, and the radiologist's report can be printed or digitally faxed by the workstation after authorization by the radiologist. The workstation has improved the organization of sonographic data, facilitated serial quantitative analysis, supplemented educational resources for our staff radiologists and residents, reduced transcription errors and transcription delays, and shortened to minutes the time necessary to deliver precise examination results to clinicians. This model is suitable for use in many areas in a radiology department. PMID- 1442411 TI - To telephone or not to telephone: how high is the standard? PMID- 1442412 TI - Luetic aneurysm of the innominate artery mimicking a mass in the right side of the anterior mediastinum: MR appearance. PMID- 1442413 TI - A new technique for retrieving catheter fragments in the pulmonary artery. PMID- 1442414 TI - Atypical choledochal cyst. PMID- 1442415 TI - Fat-containing collection adjacent to intrahepatic inferior vena cava: sonographic detection and characterization. PMID- 1442416 TI - Duplicated gall bladder and situs inversus: findings on sonography and scintigraphy. PMID- 1442417 TI - Hydatid cyst of spleen with bull's-eye appearance on imaging. PMID- 1442418 TI - Polyp arising in a colonic diverticulum. PMID- 1442419 TI - Congestive heart failure in a patient with autosomal dominant polycystic kidney disease. PMID- 1442420 TI - Late total closure and caudal migration of an LGM caval filter. PMID- 1442421 TI - Dermoid mesh: a sonographic sign of ovarian teratoma. PMID- 1442422 TI - Stress fracture detected sonographically. PMID- 1442423 TI - Pneumocephalus due to barotrauma: CT demonstration. PMID- 1442424 TI - Extradural schwannoma manifested as an expansile vertebral lesion. PMID- 1442425 TI - Inadvertent intrathecal use of ionic contrast media for myelography. AB - PURPOSE: To describe instances of inadvertent intrathecal injection of ionic contrast media and to consider treatment approaches, and diagnostic and medicolegal issues. METHODS: Ten cases of inadvertent injection, of which nine were reported to the manufacturers/authors and one appeared in the literature, are related with emphasis on similarity of reactions. RESULTS: Six criteria are enumerated and used to coin the term "ascending tonic-clonic seizure syndrome." CONCLUSIONS: Therapeutic possibilities seem limited, but several methods for controlling seizures are suggested. The importance of identifying the contrast material is underscored. Awareness of the grave possibility of administering the wrong contrast material is the first step in avoiding this problem; awareness of the symptoms is the first step toward therapy. PMID- 1442426 TI - High performance liquid chromatography with multiwavelength detection: a technique for identification of iodinated x-ray contrast agents in human body fluids and brain tissue. AB - PURPOSE: Several cases of a severe adverse reaction, referred to as "ascending tonic-clonic seizure syndrome," have been reported after administration of water soluble iodinated x-ray contrast agents for myelographic examinations. Because of the bizarre reactions, the identities of the causative contrast media were questioned. METHODS: Analyses of biologic materials from four of these patients were performed by using reverse-phase high-performance liquid chromatography. The chromatographic system was equipped with a fast-scanning UV-visible detector for the analysis of the UV-spectra of the chromatographic peaks. RESULTS: The analyses revealed that the nonionic contrast agents iohexol or ioversol were not present in detectable amounts in any of the samples. On the other hand, the chromatographic analyses revealed peaks that cochromatographed with and showed the same UV-spectra as the ionic agents diatrizoate, metrizoate, and ioxitalamate. CONCLUSION: The results indicate inadvertent injection of ionic contrast medium in all four cases. PMID- 1442427 TI - Computer-based tutorial in MR imaging. AB - PURPOSE: To test the effectiveness of customized software as a teaching tool to help the novice understand basic physics concepts underlying the creation of MR images via various pulse sequences. METHODS: The authors have developed animating graphic and highly interactive electronic MR audiovisual software for the Macintosh computer in the C programming language, and have integrated it into the classroom setting for teaching MR imaging physics concepts such as T1, T2, T2*, proton density, RF excitation, TR, TE, TI, flip angle, static magnetic field strength, gradient magnetic fields, section thickness, number of phase-encoding gradients, number of excitations, field of view, intersection gap, receiver bandwidth, contrast agent(s), etc. The program interactively demonstrates the effects of these variables upon such imaging objectives as voxel dimensions, section quantity, total scanned volume, signal-to-noise ratio, contrast, contrast to-noise ratios, resolving power, and scan acquisition time. Partial saturation, gradient echo, inversion recovery, and fat-saturation imaging techniques are included. Written posttests on the syllabus covered in our basic MR course were administered to three groups: 43 student professionals (technologist/physicist/radiologist) (control professional group) before, 149 student professionals (exposed professional group) after the addition of the tutorial software into the MR course as an integral part of the teaching process, and a group of 200 pharmaceutical sales staff with little to no prior MR or scientific background (exposed pharmaceutical group). The scores were then evaluated and compared among the groups. One hundred ten students exposed to this software also anonymously rated the software on a 1 to 5 scale (harmful to very helpful, respectively) as to their feeling regarding its role in their MR educational experience and the ease with which they were able to understand the material covered in the basic MR course curriculum. RESULTS: Mean test scores were statistically significantly lower in the Control Professional Group (60%, +/ 2.59 standard error of the mean (SEM)) than in either the Exposed Pharmaceutical (73% +/- 0.75 SEM) or Exposed Professional Groups (77% +/- 0.99 SEM). The mean subjective assessment score regarding the software was 4.8 (scale 1 to 5). CONCLUSION: This custom-developed interactive MR tutorial software is demonstrated to be effective in assisting even those new to MR imaging in understanding the concepts underlying MR imaging physics in a manner that is felt to be significantly more palatable than lectures, articles, and/or textbooks alone. PMID- 1442428 TI - MR proton spectroscopy in multiple sclerosis. AB - PURPOSE: To elucidate the natural history of visualized MR abnormalities in patients with multiple sclerosis using proton spectroscopy. METHODS: MR imaging and proton spectroscopy (1H spectroscopy) were performed on 16 patients with clinically definite multiple sclerosis. All patients received gadopentetate dimeglumine (Gd-DTPA). RESULTS: Decreased levels of N-acetylaspartate (NAA) were demonstrated in 17 out of 21 lesions. No correlation was found between decreased NAA and Gd-DTPA enhancement. In five out of seven enhancing lesions, abnormal 1H spectra with extra peaks (termed marker peaks) at 2.1-2.6 ppm (ranging in absolute concentration from 10-50 mM protons) were observed. In nine out of 14 unenhancing lesions, no elevated marker peaks were observed. In the five other unenhancing lesions, the levels of these marker peaks were generally lower than the enhancing group. No correlation was found between the NAA levels and the levels of the marker peaks. We suggest two distinct biochemical processes: 1) decreased NAA reflecting neuronal cell loss, and 2) elevated marker peaks reflecting ongoing demyelination. CONCLUSIONS: Based upon these observations we infer that 1) the majority of enhancing lesions are demyelinating with extra peaks at 2.1-2.6 ppm representing a marker of this process, 2) enhancing lesions without this marker most likely represent edematous regions without significant demyelination, and 3) demyelination may be long in duration compared with transient blood-brain barrier disruption manifested by Gd-DTPA enhancement. Our results suggest that 1H spectroscopy has the ability to further categorize MR demonstrated enhancing and unenhancing lesions in patients with multiple sclerosis and that it may be more sensitive than contrast enhancement in revealing the true time course of demyelination. PMID- 1442429 TI - MR imaging in acute multiple sclerosis: ringlike appearance in plaques suggesting the presence of paramagnetic free radicals. AB - MR studies in three patients with multiple sclerosis have shown clearly defined rings within plaques of demyelination, having signal characteristics consistent with the presence of paramagnetic material. It is suggested that these appearances represent the presence of free radicals in the macrophage layer forming the margin of an acute plaque. PMID- 1442430 TI - Fulminant multiple sclerosis. PMID- 1442431 TI - Cranial hypertrophic interstitial neuropathy. AB - The authors describe a patient with complex cranial neuropathy caused by pathologically proved hypertrophic interstitial neuropathy. Plain and contrast enhanced MR studies were performed prior to surgical exploration. Surgical complications caused the patient's death and a complete pathology study was done. Though nonspecific, MR proved helpful in determining the extent of disease and areas of anatomic involvement. PMID- 1442432 TI - Temporary balloon occlusion of the carotid artery combined with brain blood flow imaging as a test to predict tolerance prior to permanent carotid sacrifice. AB - PURPOSE: To describe the technique of using SPECT brain blood flow imaging to identify patients at risk for having strokes after balloon or surgical ligation of an internal carotid artery. PATIENTS AND METHODS: 29 patients underwent temporary balloon occlusion of the internal carotid artery and blood flow imaging studies were obtained prior to sacrifice of the vessel; 11 internal carotid arteries were indeed sacrificed and form the basis of our study. Follow-up of these patients ranged from 3 to 65 days. RESULTS: Three groups emerged: group I, patients with symptoms during occlusion and an abnormal blood flow study (one patient); group II, patients with no symptoms during the occlusion but with an unequivocally abnormal blood flow study (two patients); group III, patients without symptoms during occlusion and a normal or slightly abnormal blood flow study (eight patients). CONCLUSION: Carotid sacrifice without initial and temporary balloon occlusion is unnecessarily risky. Imaging of blood flow in the brains of these patients can further improve the safety of occlusion procedures in the internal carotid artery. PMID- 1442433 TI - Delayed venous occlusion following embolotherapy of vascular malformations in the brain. AB - PURPOSE: To describe the nature and features of delayed venous thrombosis following embolization of arteriovenous fistulae. METHODS: Retrospective review of the available clinical history, details of embolization procedures, and results of follow-up angiography were carried out on all embolization procedures performed on high-flow vascular malformations of the brain done at our institution since 1987. RESULTS: Four patients were identified who had delayed (greater than 1 week) venous thrombosis/occlusion after embolization of the malformation associated with neurologic complications. Two patients had arteriovenous fistula and two had vein-of-Galen malformations. These patients had no untoward embolization of the venous outlet as a cause of the venous occlusion. CONCLUSIONS: It is postulated that thrombosis in the arteriovenous fistula group was induced by conversion (due to embolization) of a patulous high flow venous outlet into a slow flow system; in the vein-of-Galen group, the occlusion was thought to be due to high-flow venopathy. PMID- 1442435 TI - Use of the delayed mask for improved demonstration of aneurysms on intraarterial DSA. AB - PURPOSE: We retrospectively explored the use of the delayed mask technique for intraarterial digital subtraction angiography (IADSA) to demonstrate the anatomy of aneurysm necks. METHODS: The delayed mask technique was utilized in 22 patients who had craniotomies for aneurysms demonstrated at angiography. The operative notes were compared to the angiographic findings of both the traditionally masked IADSA and the delayed mask IADSA. In addition, an in vitro model was constructed to examine the relationship between the size of the aneurysm neck and the ability to indirectly define its anatomy by demonstrating the flow jet. RESULTS: In 12 of 22 cases, the delayed mask technique demonstrated a systolic jet that was not demonstrated by traditional subtraction techniques. In nine of 12 cases, the delayed mask technique gave more specific information regarding the size, location, and orientation of the aneurysm neck. CONCLUSION: The delayed mask technique can add important information regarding the anatomy of aneurysm without adding time or risk to the procedure. PMID- 1442434 TI - Color-flow Doppler sonography in the identification of ulcerative plaques in patients with high-grade carotid artery stenosis. AB - PURPOSE: To assess the ability of color-flow Doppler sonography (CFDS) to detect plaque ulcerations in patients who had high-grade to thread-like carotid artery stenosis and who underwent carotid endarterectomy. METHODS: CFDS is a noninvasive diagnostic technique that allows, in addition to spatial visualization of blood flow, the identification of abnormal blood flow patterns such as vortex formation. There is evidence that pathologic anatomic changes in the vascular wall (such as ulcerations) may result in characteristic hemodynamic alterations. Therefore, solely hemodynamic criteria (detection of vortices) were used to diagnose ulceration. The results of preoperative examinations were compared to the intraoperative findings in 89 patients in a prospective and blinded way. RESULTS: CFDS proved highly sensitive (95.3%), specific (93.5%), and accurate (94.0%) for demonstrating ulcerative plaques. CONCLUSION: CFDS may be of significant advantage for examining plaque morphology in patients who have high grade internal carotid artery stenosis, and in whom accurate, noninvasive diagnosis of plaque ulceration was previously difficult, if not impossible. PMID- 1442436 TI - Internal carotid artery occlusion due to idiopathic cranial pachymeningitis. AB - A 35-year-old black woman had a 6-month history of headaches and a 1-month history of abducens nerve palsy. MR showed a mass in the sella and cavernous sinuses with encasement of the carotid artery. The mass enhanced intensely and homogeneously with Gd-DTPA. Arteriography revealed complete occlusion of the left internal carotid artery and severe stenosis of the C5 and C6 segments of the right internal carotid artery. Transsphenoidal biopsy of the mass led to the diagnosis of idiopathic cranial pachymeningitis. PMID- 1442437 TI - Prediction of neurologic outcome in acute spinal cord injury: the role of CT and MR. AB - PURPOSE: 1) To determine whether MR appearances of the spinal cord in acute trauma correlate with clinical prognosis, and 2) to identify other MR and CT prognostic factors in acute spinal trauma. METHODS: Retrospective evaluation of MR, CT, and clinical examinations in 32 acute spinal trauma patients examined between 1987 and 1990. RESULTS: All 21 patients with abnormal spinal cords on MR had complete motor paralysis at presentation, compared to only three of 11 patients with normal cords. Whereas cord transection and hemorrhagic contusion had poor prognoses, 73% of patients with cord edema and 100% of patients with normal cord had useful motor function at outcome. At follow-up MR, areas of cord contusion developed into cysts, while edema resolved, leaving residual areas of myelomalacia. Associated spinal fractures, ligament injury, and cord compression were associated (P < .05) with a worse prognosis. Spondylotic changes were a significant risk factor for spinal cord injury, mediated by cord compression. CONCLUSIONS: MR and CT are valuable techniques for quantifying injury and predicting prognosis in acute spinal trauma. PMID- 1442438 TI - Subfrontal recurrence of medulloblastoma. PMID- 1442439 TI - Unusual subcutaneous sarcoidosis of the face. AB - Two unusual cases of sarcoidosis manifesting as subcutaneous masses of the face are reported: in the first, the lesion occurred at the site of an osteotomy for rhinoplasty and was the initial clinical manifestation of sarcoidosis; in the second, the skin lesion was part of a multisystemic disease. The cases were documented with CT. Sarcoidosis should be added to the differential of soft tissue masses of the face. PMID- 1442440 TI - Perioptic cyst distal to optic nerve meningioma: MR demonstration. AB - Dilation of the subarachnoid space between the distal edge of an optic nerve sheath meningioma and the eyeball has previously been observed during surgery and considered a rare finding. We observed such perioptic cysts in seven patients with optic nerve meningioma and describe the MR features of this finding. PMID- 1442441 TI - Anomalous origin of the posterior inferior cerebellar artery from the internal carotid artery. AB - A rare anomalous origin of the posterior inferior cerebellar artery arising from the internal carotid artery is described. The embryologic explanation postulated is the persistence of a primitive communicating vessel (presegmental artery) between the anterior and posterior circulation. PMID- 1442442 TI - Chordomas of the skull base: MR features. AB - PURPOSE: To characterize the MR features of skull base chordomas with regard to signal intensity, size, position, extension, and Gd-DTPA enhancement. PATIENTS AND METHODS: The MR imaging studies of 28 patients with surgically proven chordomas of the skull base were retrospectively reviewed. Twenty-two of these patients received intravenous administration of Gd-DTPA. RESULTS: On short TR/short TE images, chordomas generally had low to intermediate signal. On long TR/long TE images, chordomas generally had very high signal that was heterogeneous in 79%. After Gd-DTPA administration, all chordomas demonstrated some degree of contrast enhancement. In most cases, enhancement was demonstrated throughout most of each tumor in a heterogeneous pattern. Chordomas were associated with MR findings of displacement and encasement of vessels, and frequent extension into adjacent structures such as the cavernous sinus, sella, nasopharynx, and hypoglossal canal. CONCLUSION: The MR characterization of the position and extent of these neoplasms played an important role in determining the optimal surgical approaches for gross total tumor resection. PMID- 1442443 TI - Highlights of the 30th Annual Meeting of the American Society of Neuroradiology. PMID- 1442444 TI - Highlights of the scientific exhibits of the 30th Annual Meeting of the American Society of Neuroradiology. PMID- 1442445 TI - R. Gilberto Gonzalez, PhD, MD: corecipient of the Cornelius Dyke Award for 1992. PMID- 1442446 TI - Frank J. Lexa, MD: corecipient of the Cornelius Dyke Award for 1992. PMID- 1442447 TI - Pneumosinus dilatans and arachnoid cyst. PMID- 1442448 TI - [Epidemiological study of asthmatic crises in a maternal-child emergency service]. AB - In our region, allergic respiratory diseases affects over 55% of the child up to 5 years. This could be attributed to some peculiarities of our region, such as consanguinity, climate and predominant sensitisation to dermatophagoides mite. We made an epidemiologic study on the bronchospasm urgent cases attended in the Urgency Unit of our Maternal-Child Hospital in Las Palmas. We took 935 patients with a mean age of 32.36 months with acute attacks of bronchospasm, and found no significant difference between patients from the Northern and Southern zones of the island. Bronchospasm cases were more frequently observed in Autumn and Winter. We discuss here about the possible causing agents involved and want to draw attention to the need of education for our patients' parents for them to learn antiasthmatic medication and how to use it, before going to the Urgency Unit of any Hospital. PMID- 1442449 TI - Evaluation of serum total IgE in Chinese allergic children using different assays. AB - Since differences in HLA groups have been found in Chinese populations, as well as differences in the values of total IgE in China, Japan and Thailand, a study has been done in 44 Chinese children, all of them with a history of atopic conditions divided into five groups: asthma, rhinitis, conjunctivitis, allergic bronchitis and atopic dermatitis. 34 of them were positive against D. pteronyssimus, 8 against cats, 3 against dogs and 3 against fish. The only adult patient studied was positive against gramineal plants (all positivities were tested with the prick test). IVT ELISA Screen is performed against 10 allergens, as well as 3 M FAST-Test and 3 M Total IgE FAST Plus Test. The results show that the majority of children had an elevation of the total IgE in the three tests. There is quite a good agreement between FAST and IgE-IVT and a better correlation between IgE-IVT and IgE FAST Plus. The correlation between IgE FAST and IgE FAST Plus was excellent. PMID- 1442450 TI - Reduction in the oral doses of theophylline in asthmatic children during concomitant treatment with ketotifen. AB - Sixteen children with moderate or severe bronchial asthma underwent a double blind study receiving either ketotifen (K) or placebo (P) in order to verify the sparing effect of K on theophylline. The study lasted 18 weeks. Slow release theophylline was administered to all patients at a dose of 300 mg every 12 hours for the first six weeks of the study ("washout"). From the seventh week on, eight patients received K (1 mg, 2x/day) and the others P. The theophylline dose was maintained and reduced every 4 weeks to 200 mg and 100 mg. The initial clinical characteristics were identical in both groups. The serum levels of theophylline decreased below the ideal range (less than 10 mcg/ml) in groups K and P with a 100 mg dose of theophylline. However, in group K patients, fewer reported worsening of symptoms (number of days with cough and/or wheeze, altered daytime or nighttime peak expiratory flow rate and consumption of beta agonist) when compared to group P. Increased PC20 of methacholine only occurred in group K patients. PMID- 1442451 TI - Improvement of fog and exercise-induced bronchoconstriction after local and subcutaneous immunotherapy in mite asthma. AB - We compared the changes of non-specific bronchial hyperreactivity to methacholine, UNDW and exercise in 2 groups of patients with mite asthma treated with local immunotherapy (LIT group: 12 patients) and subcutaneous immunotherapy (SIT group: 8 patients) for 1 year. Bronchial challenges were done 1 week before the beginning and 1 week after the end of 1 year of treatment. The results showed a reduction of bronchial hyperreactivity to methacholine in the LIT group (PD 20FEV1 before: 223 +/- 193, after: 434 +/- 548) but not in the SIT group (PD 20FEV1: before: 143 +/- 188, after: 125 +/- 121) but the difference was not statistically significant. Exercise-induced bronchoconstriction completely disappeared in all the patients of LIT group (8/8) although only in 2 out of 4 patients of SIT group. Water-induced bronchoconstriction improved in 66% of LIT group (4/6) compared with none of SIT group (0/4). We conclude that, with the protocol of the present study, LIT is able to improve, more than SIT, non specific bronchial hyperreactivity evaluated with osmotic stimuli as exercise and UNDW but not with pharmacologic stimuli as methacholine. PMID- 1442452 TI - IgG4 antibodies and bronchial asthma. PMID- 1442453 TI - [Asthma caused by culinary spices]. PMID- 1442454 TI - Physician heal thyself (and thy colleagues). PMID- 1442455 TI - Report QQ of the Board of Trustees (I-91). Health Access America refinements December 1991. PMID- 1442456 TI - Photorefractor for detection of treatable eye disorders in preverbal children. AB - Abnormalities of the optical media or alignment of the eyes during the period of visual immaturity may produce pathologic changes in the brain resulting in the clinical entity of subnormal vision known as amblyopia. Efforts to prevent visual deterioration or restore normal acuity where amblyopia exists require early diagnosis and treatment. Although amblyopia affects between 1% and 5% of children, it is estimated that at most one-fourth of preschool children are screened for this major treatable eye disorder. Simultaneous photography of the corneal and fundus reflex from both eyes using an offaxis flash photorefractor appears to be a practical, efficient, and effective method of eye-screening in pre-verbal children. Previous studies of this modality have dealt with populations referred to ophthalmology centers. We report the results of a masked validation of a commercially available photorefractor in an unselected group of children between the ages of 6 months and 6 years. PMID- 1442457 TI - Health care 2000? PMID- 1442458 TI - The Americans with Disabilities Act. PMID- 1442459 TI - Patient safety and physician advocacy. PMID- 1442460 TI - Contrast sensitivity vision testing. PMID- 1442461 TI - Foreign body mimicking colon cancer. PMID- 1442462 TI - Diary of a week in practice. PMID- 1442463 TI - Parapneumonic empyema in children: diagnosis and management. AB - Parapneumonic effusion can be a significant problem if it is not recognized and treated promptly. The amount of pleural fluid at presentation is usually small and may not be detected on physical examination. If pleural fluid is seen on radiographs, thoracentesis must be performed. Early, free-flowing parapneumonic effusions usually respond clinically to antibiotic therapy without the necessity of draining the pleural space. Distinguishing between exudative effusion and empyema is crucial. Failure of effusion or empyema to respond to the treatment is usually due to failure to adequately drain the pleural space or inappropriate antibiotic therapy. If chest tube drainage does not result in a lower temperature and an appropriate clinical response within a few days, further evaluation by computed tomographic scanning and surgical consultation are indicated. In patients with pleural effusion and empyema that responds poorly to medical and/or surgical therapy, underlying causes or associated debilitating disease should be excluded. PMID- 1442465 TI - Adverse psychiatric effects of systemic glucocorticoid therapy. AB - Glucocorticoid therapy causes psychiatric side effects in many patients. Although psychiatric side effects occur most commonly in women and middle-aged patients, no clinical features have been identified to predict which patients are at risk. The most frequent side effects are mood changes ranging from mild euphoria to hypomania, but other reactions, including depression, dementia and psychosis, are possible. The incidence of psychiatric side effects is directly related to dosage. The mechanism by which glucocorticoids produce psychiatric symptoms is probably multifactorial, including both direct and indirect effects on the brain. Psychiatric symptoms usually resolve with dosage reduction or controlled withdrawal of glucocorticoids, but antipsychotic medication may be indicated if symptoms are severe or prolonged. PMID- 1442464 TI - Sacroiliac sprain: an overlooked cause of back pain. AB - Since sacroiliac sprain syndrome is not a common disorder, it may be overlooked as a cause of low back pain. Even though the sacroiliac joint is very strong, it can incur painful injury. The diagnosis of sacroiliac sprain syndrome requires more than just tenderness on palpation of the sacroiliac area. Certain maneuvers, such as Patrick's test and the sacroiliac compression test, are useful in establishing the diagnosis. Proper treatment consists of bed rest, heat, nonsteroidal anti-inflammatory drugs and muscle relaxants. Physical therapy and manipulation may also help. In recalcitrant cases, injection of the sacroiliac joint with a corticosteroid and a local anesthetic can be effective. PMID- 1442466 TI - Genodermatoses with malignant potential. AB - Disease-associated malignancy may occur in several inherited conditions with dermatologic manifestations. These genodermatoses include nevoid basal cell carcinoma syndrome, Cowden's disease, multiple endocrine neoplasia syndromes, neurofibromatosis and Peutz-Jeghers syndrome. Although most of these genodermatoses are rare, recognition of their cutaneous features can facilitate early diagnosis of the systemic condition and surveillance for neoplasm. Appropriate evaluation of the patient's family, as well as genetic counseling, should be performed when the diagnosis of a genodermatosis with malignant potential is established. PMID- 1442467 TI - Sequelae of minor traumatic brain injury. AB - Minor traumatic brain injury is the most common type of traumatic encephalopathy, with approximately 290,000 to 325,000 new cases occurring each year. Recent research has suggested that both anatomic factors (acceleration-deceleration injury, contusions) and neurotransmitter factors (cholinergic systems) may contribute to the pathologic sequelae. Symptoms may be broadly categorized as physical, behavioral/affective, cognitive and integrative. Patients with mild brain injury may demonstrate significant attention and information-processing impairments in the absence of apparent neurologic problems. Most symptoms abate within the first few months, but a sizable subgroup of patients remain symptomatic up to one year or more. Evidence suggests that patients whose symptoms persist are not simply "neurotic." Rehabilitation efforts should focus on proper evaluation, reassurance, education, support and monitoring of progress. PMID- 1442468 TI - Managing the difficult physician-patient relationship. AB - A difficult physician-patient relationship can have significant consequences for both the physician and the patient. Difficult relationships can lead to frustrating, dissatisfying, adversarial and expensive medical care. The difficult relationship is often a consequence of a breakdown in communication between physician and patient. Specific causes include technical communication barriers, difficulty in discussing certain topics, unmet or violated norms and expectations (both the physician's and the patient's) and a mismatch between the physician's and the patient's personality styles. Management goals for the difficult relationship include maintaining professional self-esteem, maintaining physician patient continuity, minimizing the "medicalization" of the problem by limiting the use of tests and procedures, and minimizing hospitalization and referral. It is also important to remember that although the relationship may continue to be frustrating or conflictual, it can be effectively managed with appropriate strategies. PMID- 1442469 TI - Recommended core educational guidelines for family practice residents. Research and scholarly activity. American Academy of Family Physicians. PMID- 1442470 TI - NIH releases consensus statement on gallstones, bile duct stones and laparoscopic cholecystectomy. PMID- 1442471 TI - Tuberculosis update. PMID- 1442472 TI - Diagnostic hysteroscopy. AB - The hysteroscope is a valuable tool for selective viewing of the uterine cavity and the endocervical canal. With smaller-diameter scopes, hysteroscopy can be performed in the office setting, often without the need for cervical dilatation or local anesthesia. Controlled-rate CO2 insufflators allow safe distention of the uterine cavity with minimal side effects. Indications for office hysteroscopy include the evaluation of abnormal uterine bleeding, genital carcinoma and infertility and the investigation of a "lost" intrauterine device. Hysteroscopy is an adjunct to endometrial sampling, dilatation and curettage, hysterosalpingography and cervical cytology. PMID- 1442473 TI - Expanding applications of the 12-lead ECG in suspected acute infarction. AB - In the setting of acute myocardial infarction, the importance of the 12-lead electrocardiogram has increased tremendously. In addition to facilitating diagnosis of acute ischemic syndromes, including acute myocardial infarction, the 12-lead electrocardiogram may provide invaluable assistance in determining which patients are most suitable for thrombolytic therapy, and it may provide information that is useful in prognostic stratification. PMID- 1442474 TI - The elimination diet as a diagnostic tool. AB - Many family physicians overlook the role that food and food additives play in health problems. An elimination diet is a safe and cost-effective method of evaluating adverse reactions to foods in some patients with common medical problems. Patients whose symptoms improve or clear while they are on the diet are then challenged with the omitted foods one at a time to establish food-symptom relationships. PMID- 1442475 TI - Update on hormone replacement therapy. AB - The well-recognized benefits of hormone replacement therapy include relief of vasomotor symptoms, alleviation of psychogenic manifestations, prevention of atrophic vaginitis, prevention and treatment of osteoporosis, and prevention of cardiovascular disease. Risks can be minimized by proper evaluation and appropriate hormone replacement. When an adequate dosage of estrogen is given, the added progestogen does not adversely affect lipid levels. When progestogens are added to estrogen replacement therapy, the incidence of endometrial cancer is lower in postmenopausal women receiving this form of therapy than in untreated postmenopausal women. Although the risk of breast cancer is a matter of controversy, it does not seem to increase with estrogen therapy; the addition of progestogen may decrease the risk for some women. The prognosis for breast cancer is improved in women receiving hormone replacement therapy. PMID- 1442476 TI - The conservative coronary angioplasty strategy after thrombolysis for acute myocardial infarction: immediate and short-term results. AB - The in-hospital and short-term follow-up results of a conservative coronary angioplasty approach in 354 consecutive patients treated after thrombolysis for acute myocardial infarction were compared with results obtained in 408 control noninfarcted patients treated for the classical indication of myocardial ischemia. Only 20% of the study patients underwent angioplasty during the initial hospitalization period and the clinical success rate was 93% versus 95% in the control group (p = NS). No significant differences in the total number of in hospital untoward events were observed (10.2% and 7.6%, respectively). During a 7.4 +/- 1.5 month follow-up period, the total number of adverse events was only 16.9% in the study patients but it was 27.8% in the control group (p < 0.001). There were no significant differences in death, myocardial infarction, or coronary surgery as individual events, but repeat angioplasty was less frequent in the study group (14.0% versus 21.5%, p < 0.01). Thus in-hospital results in patients undergoing angioplasty on a deferred basis after thrombolysis for myocardial infarction were largely comparable with those results obtained in noninfarcted patients. Moreover, short-term clinical follow-up events were reduced when compared with the control group, an observation apparently largely related to the subgroup without clinical evidence of residual ischemia. PMID- 1442477 TI - Effects of intraaortic balloon pumping on coronary hemodynamics after coronary angioplasty in patients with acute myocardial infarction. AB - It has been reported that intraaortic balloon pumping can prevent reocclusion after coronary angioplasty for acute myocardial infarction. The speculated mechanism has been the production of markedly enhanced diastolic coronary perfusion pressure; however, most studies have reported that intraaortic balloon pumping has little effect on coronary blood flow. To assess the effectiveness of this procedure, we studied 12 patients with acute anterior myocardial infarction who were undergoing coronary angioplasty and intraaortic balloon pumping. After successful angioplasty, coronary blood flow velocity was measured with a coronary Doppler catheter before and during intraaortic balloon pumping. Although mean coronary blood flow velocity was unchanged, intraaortic balloon pumping increased peak coronary blood flow velocity from 34.6 +/- 5.0 cm/sec (mean +/- SEM) to 46.7 +/- 5.8 cm/sec (p < 0.005). Such an increase in peak coronary blood flow velocity seemed to be a mechanism by which intraaortic balloon pumping could prevent reocclusion after coronary angioplasty for acute myocardial infarction. PMID- 1442478 TI - Reduced infarct size in nonreperfused myocardial infarction by combined infusion of isosorbide dinitrate and streptokinase. AB - The value of thrombolytic therapy in myocardial infarction is well established, while any beneficial effect of adjunct therapy is more uncertain. In a double blind, randomized, parallel-group study the effect of combined intravenous infusions of streptokinase and isosorbide dinitrate (ISDN) on enzyme-estimated infarct size was investigated. One hundred consecutive patients with strong clinical and electrocardiographic suspicion of myocardial infarction, admitted to the coronary care unit within 8 hours after the onset of symptoms, were given a streptokinase infusion of 1.5 million units for 1 hour and a titrated dose of ISDN or placebo for 48 hours. From isoenzyme B of creatine kinase (CK-B) values measured every 4 hours, the infarct size was calculated and the possible presence of reperfusion was evaluated. The infarct size in patients receiving ISDN infusion was reduced (p = 0.04, one-sided test) compared with placebo. By subdividing the patients according to whether or not reperfusion had occurred, the infarct size appeared to be similar following ISDN and placebo in patients with reperfusion (419 versus 369 U/L), whereas the infarct size in patients not reperfused was markedly reduced after treatment with ISDN (223 versus 1320 U/L, p = 0.003). In conclusion, the present study demonstrates that the infarct size may be reduced by other means than reperfusion and it supports the use of combined infusion of thrombolytic agents and nitrates in patients with suspected myocardial infarction. PMID- 1442479 TI - Active compression-decompression resuscitation: a novel method of cardiopulmonary resuscitation. AB - Chest compression is an important part of cardiopulmonary resuscitation (CPR), but it only aids circulation during a portion of the compression cycle and has been shown to only minimally increase blood flow to vital organs. The purpose of this study was to quantitate the short-term hemodynamic effects of CPR with a hand-held suction device that incorporates both active compression and decompression of the chest. The suction device was applied to the middle of the sternum and compared with standard manual CPR in eight nonventilated anesthetized dogs. Coronary perfusion pressure, systolic and diastolic aortic pressures, right atrial diastolic pressure, and the velocity time integral (an analog of cardiac output), which were obtained by means of transesophageal pulsed wave Doppler echocardiography from the main pulmonary artery, were measured every 30 seconds during CPR. Minute ventilation was measured over the last minute of each CPR technique. Both active compression-decompression CPR and standard CPR were sequentially performed for 2 minutes in random order 30 seconds after induced ventricular fibrillation. The CPR techniques consisted of 100 compressions per minute, with a compression depth of 1.5 to 2 inches and a 50% duty cycle. Coronary perfusion pressure, velocity time integral (cardiac output analog), minute ventilation, and systolic arterial pressure were all significantly improved by active compression-decompression CPR when compared with standard CPR. We conclude that active compression-decompression CPR is a simple technique that appears to improve coronary perfusion pressure, systolic arterial pressure, cardiac output, and minute ventilation in nonventilated animals when compared with standard CPR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442480 TI - Myocardial hibernation identified by hyperbaric oxygen treatment and echocardiography in postinfarction patients: comparison with exercise thallium scintigraphy. AB - To evaluate the potential for hyperbaric oxygen (HBO) to produce transient improvement in function in areas of myocardium ischemic at rest (hibernating myocardium), 24 patients were studied within 1 week of acute myocardial infarction. Results were compared with single-photon emission computed tomography (SPECT) thallium-201 exercise scintigraphy. Echocardiography demonstrated improved contraction following HBO in 20 of 62 damaged left ventricular segments in 12 of 24 patients. Thirteen of the 28 segments and 9 of the 14 patients showing reversible ischemia on SPECT imaging showed improvement with HBO. There were eight segments with apparently normal resting contraction that showed a reversible thallium defect. Of 42 segments with fixed contraction abnormalities following HBO, eight had reversible thallium defects, four had normal thallium kinetics, and 30 had fixed thallium defects. Thus hyperbaric oxygen can demonstrate improvement in function in some segments of left ventricle after infarction. There is some overlap with viability as determined by thallium studies, but the two techniques may be complementary in describing myocardial ischemia. PMID- 1442481 TI - Long-term follow-up after percutaneous transluminal coronary angioplasty in patients with single-vessel disease. AB - Seven hundred ninety-eight patients with symptomatic single-vessel disease who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1977 and 1985 were reevaluated by questionnaire 78 +/- 23 months after dilatation. Indication for PTCA was stenosis of > or = 70%, anginal symptoms, and objective signs of myocardial ischemia. The immediate success rate was 81.2%, and severe complications occurred in 7.1%, which included two fatal complications (0.3%). Repeat angiograms were performed in 582 of 648 patients who underwent successful dilatation and showed restenosis in 143 cases (24.6%). Within 1 year after the first dilatation, 586 patients had been successfully revascularized by PTCA (i.e., there was no evidence of restenosis or redilatation was successful), and 113 patients had undergone bypass surgery. The remaining 99 patients were treated medically if PTCA was unsuccessful or if restenosis (> or = 70%) that was not amenable to redilatation was present. The 8-year overall survival probability was 91.7%, and cardiac survival was 95.5%. The 8-year event-free survival probability was 52.7% for all patients: 62.5% in patients who had successful PTCA and 14.5% in patients who had unsuccessful PTCA (p = 0.0000). The cardiac survival probabilities of patients with lasting PTCA success at 1 year and of surgically treated patients were significantly better than those of patients who did not have successful revascularization (at 8 years 97.2% and 98.1% vs 88.9%; p < 0.04). Late events (> or = 1 year) occurred more often in patients who did not have successful revascularization compared with patients who had successful PTCA (at 8 years 57.9% were event-free vs 74.4%; p < 0.0001); even fewer late events were observed in surgically treated patients (at 8 years 88.2% were event-free; p < 0.004). Cox's proportional hazards regression analysis revealed left ventricular ejection fraction and revascularization status at 1 year as determinants of overall, cardiac, infarct-free, and event-free survival probabilities. At the time of reevaluation significantly more patients in the successful PTCA subgroup were still free of symptoms or had experienced improvement than patients in the bypass or medical subgroups (86.8% vs 68.9% and 59.5%, respectively; p < 0.0001), and more patients in the successful PTCA subgroup were still working (75.4% vs 53.3% and 56.9%, respectively; p < 0.001). We concluded that patients with single-vessel disease who have undergone successful dilatation have an excellent long-term prognosis with regard to survival, cardiac symptoms, and vocational status.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1442482 TI - Long-term efficacy of triple-vessel angioplasty in patients with severe three vessel coronary artery disease. AB - Between May 1982 and December 1988, a total of 103 patients underwent angioplasty of all three major coronary arteries at a single institution. Angiographic success was achieved in 334 of 352 vessels (95%) and in 441 of 460 lesions (96%). No patients required urgent bypass surgery, and none died during the procedure; six had non-Q wave infarctions. The mean length of follow-up time was 49 +/- 15 months (range 28 to 107 months). There have been 11 deaths, and one patient has undergone cardiac transplantation. Thirty-six patients had a clinical recurrence; 30 had repeat angioplasty and five had bypass surgery. Another nine patients eventually had bypass surgery after the clinical recurrence. At 48 months actuarial event-free rates are myocardial infarction, 98%; bypass surgery, 88%; and death, 89%. Of 86 current survivors, 58 are in functional class O to I, 21 are in class II, and seven are in class III. PMID- 1442483 TI - Aggressive clinical pattern of angina at restenosis following coronary angioplasty in unstable angina. AB - The frequency, clinical pattern, and timing of recurrent angina following successful single-lesion percutaneous transluminal coronary angioplasty (PTCA) was assessed in a consecutive group of 104 patients with stable angina and in 85 with unstable angina. In addition, the relationship between lesion morphology and angiographic features and the pattern of recurrent angina was determined. Restenosis, defined as recurrence of symptoms with > 50% stenosis at the site of PTCA, occurred in 25 (24%) of the stable group and in 23 (27%) of the unstable group (p = NS). The pattern of angina at repeat presentation was aggressive in nature in 8% of the stable group and in 48% of the unstable group (p = 0.002). The time interval between the recurrence of symptoms and repeat coronary angiogram or PTCA was longer in the nonaggressive group than in the aggressive group, 16 +/- 12.1 and 5 +/- 6.8 weeks, respectively (p < 0.003). The key factors predicting the recurrent angina pattern identified by multiple logistic regression analysis were the angina status pre-PTCA (p = 0.001) and the presence of double-vessel disease (p = 0.01). An aggressive pattern of angina at the time of restenosis is frequent in patients with unstable angina at the time of PTCA, and close post-PTCA surveillance is necessary in these patients. PMID- 1442484 TI - Edge detection versus densitometry in the quantitative assessment of stenosis phantoms: an in vivo comparison in porcine coronary arteries. AB - The aim of this study was the in vivo validation and comparison of the geometric and densitometric technique of a computer-assisted automatic quantitative angiographic system (CAAS system). In six Landrace Yorkshire pigs (45 to 55 kg), precision-drilled phantoms with a circular lumen of 0.5, 0.7, 1.0, 1.4, and 1.9 mm were percutaneously introduced into the left anterior descending or left circumflex coronary artery. Twenty-eight coronary angiograms obtained with the phantom in a wedged intracoronary position could be quantitatively analyzed. Minimal lumen diameter, minimal cross-sectional area, percent diameter stenosis, and cross-sectional area stenosis were automatically measured with both the geometric and densitometric technique and were compared with the known phantom dimensions. When minimal lumen diameter was measured using the geometric approach, a nonsignificant underestimation of the phantom size was observed, with a mean difference of -0.06 +/- 0.14 mm. The larger mean difference observed with videodensitometry (-0.11 +/- 0.20 mm) was the result of the failure of the technique to differentiate the low lumen videodensities of two phantoms of smaller size (0.5 and 0.7 mm) from a dense background. Percent cross-sectional area stenosis measured with the two techniques showed a good correlation with the corresponding phantom measurements (mean difference between percent cross sectional area stenosis calculated from the quantitative angiographic measurements and the corresponding phantom dimensions was equal to 2 +/- 6% for both techniques, correlation coefficient = 0.93 with both techniques, SEE = 5% with the geometric technique and 6% with the densitometric approach).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442485 TI - Relationship between septal perfusion, viability, and motion before and after coronary artery bypass surgery. AB - The etiology of abnormal interventricular septal motion occurring after open heart surgery using cardiopulmonary bypass has not been clarified. Intraoperative ischemic septal injury has been proposed as one explanation for this finding. To examine this possibility, resting septal perfusion and viability were studied using rest and redistribution thallium-201 scintigraphy in 16 patients before and after coronary artery bypass surgery. The results were compared with septal motion on preoperative and postoperative resting gated blood pool scans. Preoperatively, septal thallium uptake was normal in 10 of 16 patients, and septal motion was normal in 14 of 16. Postoperatively, septal thallium uptake was normal in 11 of 16 patients, while septal motion was abnormal in all. Thus abnormal postoperative septal motion is usually associated with normal septal perfusion and viability on thallium scans and therefore is not the result of septal ischemic injury in a majority of patients. PMID- 1442486 TI - Detection of restenosis with dobutamine stress test after coronary angioplasty. AB - Dobutamine ECG tests were serially performed before, at 15 days, and at 2 and 6 months after successful coronary angioplasty in 58 patients. The dose of dobutamine was progressively increased from 5 micrograms/kg/min to a maximum of 40 micrograms/kg/min every 5 minutes, with ECG and blood pressure control. Coronary angiography was performed at the end of the study. At 15 days after coronary angioplasty, the dobutamine test was of little value for the diagnosis or prediction of restenosis. At the end of the study, both the presence of angina and the results of the dobutamine test were related to coronary angiography, and their accuracy was calculated for the detection of mild (> or = 50%) and severe (> or = 70%) restenosis or new coronary lesions. The accuracy of angina was 68% for the detection of mild lesions and 70% for that of severe lesions, whereas the accuracy of the dobutamine test was 78% for mild lesions and 80% for severe lesions. It is concluded that the dobutamine stress test is a simple and useful method for the detection of restenosis when it is performed at 2 and 6 months after coronary angioplasty. However, it cannot distinguish between restenosis or new coronary lesions. PMID- 1442487 TI - Metabolic effects of adenosine on regional myocardial ischemia by phosphorus 31 nuclear magnetic resonance spectroscopy. AB - The metabolic effects of adenosine on regionally ischemic myocardium were investigated in an open-chest rabbit model by means of phosphorus 31 nuclear magnetic resonance (NMR) spectroscopy. Sixteen anesthetized New Zealand white rabbits were subjected to thoracotomy; a reversible snare occluder was placed around a large branch of the left circumflex coronary artery, and an NMR surface coil was positioned adjacent to the myocardium perfused by this vessel. The animals were placed in a 2.0 T CSI spectrometer (GE Medical Systems, Fremont, Calif.), and baseline spectra were acquired. Eight animals were treated with intravenous adenosine (25 mg/kg), and eight rabbits served as control subjects. All animals were subjected to a 10-minute period of ischemia followed by a period of reperfusion. NMR spectra were acquired during both intervals. During the occlusion period, expected increases in inorganic phosphate levels and decreases in phosphocreatine levels were observed in both groups; however, inorganic phosphate increased less in adenosine-treated animals (adenosine: 33 +/- 2.8% total spectral area during occlusion vs control: 41 +/- 3.1%) and phosphocreatine diminished less with adenosine (adenosine: 26 +/- 3% vs control: 13 +/- 1.2%; p < 0.002). No significant differences were seen in beta-adenosine triphosphate levels. In both groups the metabolite levels during reperfusion recovered to near baseline values, although phosphocreatine remained slightly higher in the treated group during early reperfusion. An apparent cardioprotective effect of adenosine on relative phosphocreatine and inorganic phosphate levels can be observed in intact rabbits by means of phosphorus 31 NMR spectroscopy. PMID- 1442488 TI - Diagnostic and prognostic value of ambulatory electrocardiographic monitoring. AB - To evaluate the diagnostic and prognostic value of continuous ambulatory ECG (AECG) monitoring, we studied 124 patients with chest pain syndromes by stress myocardial perfusion scintigraphy (MPS) and AECG. MPS was classified as normal or with fixed or reversible defects involving one or more than one vascular territory. Positive AECGs were divided into those with mild (< or = 1.5 mm), moderate (1.5 to 2.5 mm), and severe (> or = 2.5 mm) ST segment displacement. Among 61 patients with a negative AECG, 93% had limited ischemia or normal scintigraphic studies. All 24 patients with moderately or severely positive AECGs had reversible defects on MPS. Among those with severely positive AECGs, nine (75%) had multivessel scintigraphic ischemia. Severe ST segment depression on AECG was highly related to multivessel perfusion defects and to a large amount of myocardium in jeopardy. A negative AECG generally indicated limited or absent ischemia and thus a more benign prognosis. Induced symptoms and the daily ischemic burden were not related to the severity of induced AECG or MPS abnormalities. AECG may provide independent information as to the severity and related risk of ischemia. PMID- 1442489 TI - Power law analysis of the signal-averaged electrocardiogram for identification of patients with ventricular tachycardia: effect of bundle branch block. AB - Signal-averaged ECGs that use time-domain analysis are useful for the identification of patients at risk for ventricular tachycardia (VT). Bundle branch block (BBB) and other conduction defects reduce the value of this approach, but frequency-domain analysis has shown promise in such patients. The purpose of the present study was to examine a new frequency-domain approach to signal-averaged ECGs in patients with and without BBB: power law scaling (PLS). PLS was performed by plotting the power spectrum of the entire signal-averaged ECG on a plot of log power versus log frequency and determining the slope (beta) by least-squares regression. This method was studied in 346 patients. Results of discriminant analysis revealed better sensitivity, specificity, positive predictive value, negative predictive value, and percentage correctly predicted when this method was compared with time-domain indexes. A large proportion of the variance in PLS (19%) was found to be due to findings in patients with VT; whereas the best time-domain index, duration of the filtered QRS signal, explained only 6% of the variance in the group with VT. Mean levels of PLS (+/- standard deviation) were decreased for the group with VT (-3.55 +/- 0.95) as compared with the group without VT (-4.34 +/- 0.59; p < 0.001), suggesting a decrease in the time correlation of the signal. Thus this method of frequency domain analysis of the signal-averaged ECG was useful in identifying patients with sustained VT despite the presence of significant conduction defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442490 TI - Predictors of surgical mortality and long-term results of endocardial resection for drug-refractory ventricular tachycardia. AB - The results of surgical therapy performed in 51 consecutive patients with ventricular tachycardia were reviewed to determine short- and long-term predictors of success of such therapy in preventing recurrences of life threatening ventricular arrhythmias. Of 41 patients (80%) who survived surgery, 40 had postoperative programmed stimulation and, of these patients, 78% (n = 31) had no inducible ventricular tachycardia on no antiarrhythmic therapy. This group had a very low incidence of arrhythmia recurrence, with only one nonfatal episode of ventricular tachycardia after a mean follow-up of 41 +/- 30 months. In contrast, two of the nine patients (22%) who had inducible arrhythmias postoperatively had cardiac arrest (p = 0.12). Multivariate analysis identified two significant predictors of perioperative mortality in our patients: increased duration of cardiopulmonary bypass time and increased baseline pulmonary capillary wedge pressure. It is concluded that (1) patients who do not have inducible ventricular tachycardia after arrhythmia surgery have a very low incidence of recurrent arrhythmia and (2) prolonged time of cardiopulmonary bypass and increased pulmonary capillary wedge pressure are predictive of perioperative mortality. PMID- 1442491 TI - A prospective study of the efficacy and safety of adjuvant metoprolol and xamoterol in combination with amiodarone for resistant ventricular tachycardia associated with impaired left ventricular function. AB - Combination antiarrhythmic drug therapy may be more effective than treatment with a single agent for control of refractory cases of sustained ventricular tachycardia (VT). In a prospective randomized crossover study of 20 patients with impaired left ventricular function (ejection fraction of 28% +/- 8%) and recurrent VT in spite of treatment with amiodarone, we compared the efficacy and safety of adjuvant therapy with metoprolol, 50 mg two times daily and xamoterol, 200 mg two times daily. Metoprolol caused hemodynamic deterioration in five patients, and only one also experienced intolerance to xamoterol. Sustained VT was inducible in all 20 patients who were receiving amiodarone alone but was suppressed or rendered nonsustained in 8 of 20 patients during treatment with amiodarone plus xamoterol and in 6 of 17 patients during treatment with amiodarone plus metoprolol. Addition of xamoterol restored sinus rhythm in four patients who presented with incessant VT, and metoprolol was effective for three of them. Neither beta-blocker significantly altered tachycardia cycle length or any electrophysiologic parameter other than the slowing of the sinus rate. Both beta-blockers suppressed exercise-induced VT in 3 of 4 patients, and addition of xamoterol significantly increased treadmill exercise duration (7.1 +/- 1.8 min) compared with administration of amiodarone alone (3.8 +/- 1.5 min; p < 0.01). Fourteen patients were discharged with prescriptions for amiodarone-beta-blocker combinations. During a mean follow-up period of 13 months (range, 2 to 24 months), there were three cases of recurrent VT (in all patients VT remained inducible) and no sudden deaths.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442492 TI - Subcutaneous lidocaine affects inducibility in programmed electrophysiology testing in children: a follow-up study. AB - Invasive cardiac electrophysiology testing during cardiac catheterization requires local anesthesia at the point of entry for the catheters. Frequently, lidocaine is employed for this purpose. A prospective study completed in 1990 indicated that subcutaneous administration of lidocaine adversely influenced the inducibility of arrhythmias in pediatric patients. Upon completion of that study, lidocaine concentration was reduced from 1% to 0.5%, and extra caution was taken to avoid deep penetration during administration. A follow-up, prospective study was performed to evaluate inducibility under these changed conditions. Because the depressant effect of lidocaine on inducibility was age- and weight-related, the second study group was required to have statistically indistinguishable age and weight distributions from the first group to eliminate these variables as factors in inducibility. A total of 177 subjects were collected in the second group before a periodic random computer match with the first group produced 99 individuals with the required age and weight distributions. Analysis of the electrophysiology tests in the second study revealed that: (1) incidence of inducibility was higher in the second group (58 of 99 versus 43 of 99, p < 0.05); (2) average lidocaine dose per kilogram was lower (1.8 mg/kg versus 3.28 mg/kg, p < 0.0001); (3) average lidocaine serum concentration was also lower (0.58 micrograms/ml versus 1.47 micrograms/ml, p < 0.0003); (4) in contrast to the first study, neither lidocaine dose nor serum concentration had any effect on inducibility. We conclude that the new procedures for lidocaine administration effectively removed lidocaine as a factor in inducibility. PMID- 1442493 TI - Significance of coronary angiography, left heart catheterization, and endomyocardial biopsy for the diagnosis of idiopathic dilated cardiomyopathy. AB - Many physicians assume that a reliable diagnosis of idiopathic dilated cardiomyopathy can be made by noninvasive methods, mainly echocardiography. On the other hand, use of endomyocardial biopsy in those patients who have undergone left heart catheterization and who demonstrate left ventricular dysfunction of unknown origin is increasing. Therefore the purpose of this study was to investigate the yield of that diagnostic strategy in patients with the tentative diagnosis of idiopathic dilated cardiomyopathy. Between 1980 and 1988, 3.2% of our 15,442 patients were diagnosed as having idiopathic dilated cardiomyopathy on the basis of left heart catheterizations and coronary angiograms. Idiopathic dilated cardiomyopathy was diagnosed in 444 patients on the basis of clinical data and results of noninvasive tests before catheterization, but in only 295 of these cases was the diagnosis confirmed by means of coronary angiography and left heart catheterization (predictive value of noninvasive tests is 66%). The remaining 34% of patients demonstrated extensive coronary artery disease (13%), significant valvular heart disease (11%), and other or no heart disease (10%). The diagnostic sensitivity of noninvasive tools (patient history, ECG, stress test, echocardiography) was only 59%. Left heart catheterization can easily be combined with endomyocardial biopsy. With the use of histologic techniques, specific heart muscle diseases were detectable in 3.5% of 209 patients, but in only 1% could therapeutic consequences be determined. Thus coronary angiography and left heart catheterization are mandatory for the correct diagnosis of idiopathic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442494 TI - Point mutations in mitochondrial DNA in patients with hypertrophic cardiomyopathy. AB - Recent advances suggest that mutations in nuclear DNA are involved in the etiology of autosomal dominant hypertrophic cardiomyopathy. Mitochondria have their own DNA, and mutations in mitochondrial DNA have been shown to contribute to the genesis of various diseases. In this study, we developed rapid sequencing methods with the use of a fluorescence-based sequencing system and analyzed total mitochondrial DNA of seven patients with nonautosomal dominant hypertrophic cardiomyopathy. Multiple point mutations were observed in all patients with hypertrophic cardiomyopathy, although some of them were common among the subjects examined and the others are unique to each subject. Point mutations in transfer RNA genes were observed in five of the seven patients, and point mutations that replaced conserved amino acids were also observed. These mutations may result in the impairment of mitochondrial function. According to these results, mutations in mitochondrial DNA may contribute to the genesis of some cases of nonautosomal dominant hypertrophic cardiomyopathy, and our methods may be useful for the detection of point mutations in mitochondrial DNA. PMID- 1442495 TI - Contrasting patterns of arterial and venous dilatation after intravenous captopril in patients with chronic cardiac failure and their relationship to plasma angiotensin II concentrations. AB - A 25 mg intravenous bolus injection of captopril caused an abrupt and rapid decrease in systemic vascular resistance (time to maximum effect 15 minutes), but a more gradual decrease in right atrial pressure (time to maximum effect 75 minutes) in 12 patients with chronic cardiac failure. Plasma angiotensin II concentrations fell significantly, reaching their lowest concentrations at 75 minutes after the injection of captopril, at which time systemic vascular resistance had begun to return toward control values. There was no correlation between the acute arteriodilator response and pretreatment plasma renin activity or plasma angiotensin II concentrations, or the decrease in plasma angiotensin II concentrations. There was a significant correlation between the decrease in plasma angiotensin II concentrations and the decrease in right atrial pressure (r = 0.67, p < 0.05). These findings suggest that in contrast to the venous response to intravenous captopril, the arterial response is not entirely dependent on a decrease in the circulating plasma angiotensin II concentration. PMID- 1442496 TI - Additive myocardial depressant effects of cocaine and ethanol. AB - Although significant morbidity and mortality have been associated with the combined use of cocaine and ethanol, the cardiovascular effects of this combination are unknown. In this study, the effect of ethanol on cocaine-induced cardiovascular alterations was examined in two groups (n = 8 each) of dogs, which were randomized to receive either ethanol (1.68 gm/kg intravenously) or saline solution and cocaine (2 mg/kg intravenously). Ethanol had no effect on heart rate, mean arterial pressure, or rate-pressure product; but it increased ventricular end-diastolic pressure (p < 0.05), reduced coronary diameter (p < 0.02), and decreased ejection fraction by 16% +/- 4% (p < 0.005) from baseline. Cocaine produced increases in mean arterial pressure, rate-pressure product, and left ventricular end-diastolic pressure that were similar in both groups. After administration of cocaine, left ventricular ejection fraction decreased 16% +/- 2% (p < 0.001) from the baseline value in controls and 32% +/- 5% (p < 0.0002 vs baseline; p < 0.01 vs controls) in the ethanol group. Coronary diameter decreased (p < 0.05) in both groups after administration of cocaine; however, there was no difference between groups in the response of coronary circulation to cocaine. Cocaine and ethanol depress myocardial function, and their effects are additive. Failure of ethanol to enhance cocaine-induced coronary vasoconstriction suggests that the additive myocardial depressant effect of this combination is not related to ischemia but rather to a direct toxic effect of these drugs. Individuals who combine ethanol and cocaine may be at increased risk of hemodynamic compromise. PMID- 1442497 TI - Relationship between plasma atrial and brain natriuretic peptide concentration and hemodynamic parameters during percutaneous transvenous mitral valvulotomy in patients with mitral stenosis. AB - Brain natriuretic peptide (BNP), a family of peptides with structural and biologic homologies to previously identified atrial natriuretic peptide (ANP), has been found in human cardiac tissue and plasma. To examine the secretion mechanism of these peptides, we have studied the relationship between their plasma concentrations and hemodynamic parameters before and at 0.5 and 24 hours after percutaneous transvenous mitral commissurotomy (PTMC) in 14 patients with mitral stenosis. We have also investigated the validity of measuring plasma natriuretic peptides as a means for estimating changes in hemodynamic parameters after PTMC. The procedure decreased left atrial pressure (p < 0.01) with an elevation in left ventricular end-diastolic pressure (p < 0.05). Plasma ANP levels decreased significantly after PTMC (before, 64.1 +/- 33.7 fmol/ml; at 0.5 hour, 58.9 +/- 27.7 fmol/ml; at 24 hours, 45.7 +/- 18.3 fmol/ml; p < 0.01), whereas plasma BNP levels remained unchanged after the procedure (before, 5.3 +/- 1.5 fmol/ml; at 0.5 hour, 5.6 +/- 1.9 fmol/ml; at 24 hours, 5.0 +/- 1.9 fmol/ml; p = NS). There was a significant relationship between basal plasma ANP and left atrial pressure (r = 0.88; p < 0.001), and changes in plasma ANP were correlated with those in left atrial pressure (r = 0.69; p < 0.01). Basal plasma BNP was significantly correlated with basal left ventricular end-diastolic pressure (r = 0.65; p < 0.05) but not with the other measured hemodynamic parameters or with plasma volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442498 TI - Quantification of mitral regurgitation with the proximal flow convergence method: a clinical study. AB - Accurate quantitation of valvular incompetence remains an important goal in clinical cardiology. It has been shown previously that when color flow Doppler mapping is used, simple measurements of apparent jet size do not correlate closely with regurgitant flow rate and regurgitant fraction. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Flow rate Q can be calculated as Q = 2 pi r2v(a), where v(a) is the aliasing velocity at a distance r from the orifice. In 54 patients (43 with sinus rhythm and 11 with atrial fibrillation) who had at least mild mitral regurgitation according to semiquantitative assessment, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated with the proximal flow convergence method and compared with values that were obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (Vr) as calculated by the proximal flow convergence method correlated very closely with values that were obtained by the Doppler two-dimensional method, with r = 0.93 (y = 0.95x + 0.55) and delta Vr = -0.3 +/- 4.0 cm3. Regurgitant flow rates (Q) as calculated by both methods showed a similar correlation: r = 0.93 (y = 0.95x + 54) and delta Q = -34 +/- 284 cm3/min. The correlation for regurgitant fraction (RF) as calculated by both techniques showed r = 0.89 (y = 0.98x + 0.006) and delta RF = -0.005 +/- 0.06. All correlations were slightly better for the group of patients with sinus rhythm than for the study group of patients with atrial fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442499 TI - Aortic valve prolapse with aortic regurgitation assessed by Doppler color-flow echocardiography. AB - The incidence of and the Doppler color-flow echocardiographic characteristics of aortic valve prolapse with nonrheumatic aortic regurgitation were examined. Aortic valve prolapse was observed in 21 of 243 patients (15 men and 6 women) with aortic regurgitation as detected by Doppler color-flow echocardiography (rheumatic, 112; nonrheumatic, 131) in 1247 consecutive patients. Patients with aortic valve prolapse included three patients with essential hypertension and one with annuloaortic ectasia. The remaining 17 patients (7% of those with aortic regurgitation) had no other associated cardiovascular disease (idiopathic aortic valve prolapse). Prolapse of the mitral or the tricuspid valve or both was associated with aortic valve prolapse in seven patients. Aortic regurgitation jet was markedly deviated from the axis of left ventricular outflow tract toward the anterior mitral leaflet or the interventricular septum in 17 of 21 (81%) patients with aortic valve prolapse, whereas 28 of 110 (25%) patients with nonrheumatic aortic regurgitation without prolapse and 17 of 112 (15%) patients with rheumatic aortic regurgitation without prolapse showed the deviation of regurgitant jet (p < 0.001). In conclusion, idiopathic aortic valve prolapse is one of the significant causes of aortic regurgitation, and a marked deviation of regurgitant jet is a characteristic Doppler color-flow echocardiographic finding of aortic regurgitation that results from aortic valve prolapse. PMID- 1442500 TI - Isovolumic relaxation time varies predictably with its time constant and aortic and left atrial pressures: implications for the noninvasive evaluation of ventricular relaxation. AB - The isovolumic relaxation time (IVRT) is an important noninvasive index of left ventricular diastolic function. Despite its widespread use, however, the IVRT has not been related analytically to invasive parameters of ventricular function. Establishing such a relationship would make the IVRT more useful by itself and perhaps allow it to be combined more precisely with other noninvasive parameters of ventricular filling. The purpose of this study was to validate such a quantitative relationship. Assuming isovolumic relaxation to be a monoexponential decay of ventricular pressure (pv) to a zero-pressure asymptote, it was postulated that the time interval from aortic valve closure (when pv = p(o)) until mitral valve opening (when pv = left atrial pressure, pA) would be given analytically by IVRT = tau[log(p(o))-log(pA)], where tau is the time constant of isovolumic relaxation and log is to the base e. To test this hypothesis we analyzed data from six canine experiments in which ventricular preload and afterload were controlled nonpharmacologically. In addition, tau was adjusted with the use of beta-adrenergic blockade and calcium infusion, as well as with hypothermia. In each experiment data were collected before and after the surgical formation of mitral stenosis, performed to permit the study of a wide range of left atrial pressures. High-fidelity left atrial, left ventricular, and aortic root pressures were digitized, the IVRT was measured from the aortic dicrotic notch until the left atrioventricular pressure crossover point, and tau was calculated by nonlinear least-squares regression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442501 TI - Doppler assessment of right ventricular filling dynamics in systemic hypertension: comparison with left ventricular filling. AB - To assess right ventricular filling dynamics in systemic hypertension, pulsed Doppler echocardiographic studies were obtained at the tricuspid and mitral anuli in 43 untreated hypertensive patients, aged 23 to 66 years, and in 42 age-matched normotensive control subjects. In hypertensive patients, the ratio of late to early peak filling velocity and atrial filling fraction were higher, while normalized peak filling rate, one third and one half filling fractions were lower, compared with control values. Right ventricular filling dynamics correlated poorly with age in hypertensive patients, and were unrelated to left ventricular mass or left ventricular wall thickness. Weak correlations were only found between right ventricular wall thickness and right ventricular peak late inflow velocity, first half and first third filling fractions. However, right ventricular filling dynamics were closely related to left ventricular filling dynamics in both hypertensive patients (r = 0.49 to 0.82) and normal individuals (r = 0.55 to 0.86). Thus right ventricular filling dynamics are altered in hypertension, independently of left ventricular mass or blood pressure, are weakly related to right ventricular thickness, but remain closely correlated to left ventricular filling dynamics. PMID- 1442502 TI - Cholesterol embolism: an underdiagnosed clinical entity. PMID- 1442503 TI - The clinical relevance of myocardial viability in patient management. AB - This study examined the importance of viability as a clinical issue in 532 patients with angiographically proven CAD who underwent exercise SPECT thallium imaging. Conventional 4-hour delayed images were used to differentiate scar tissue from ischemia (20 segments per patient). There were 90 patients (17%) with normal images, 274 patients (52%) with reversible defects only, and 168 patients (31%) with scar tissue either with or without associated ischemia. The patients with scar tissue were subdivided according to the number of segments with fixed defects and the number of additional reversible defects. There were 114 patients with scar tissue alone or more scar tissue than ischemia. Contrast ventriculography in these 114 patients revealed normal wall motion or ejection fraction in 50 patients. On the basis of results of thallium imaging alone, the issue of viability was probably significant in 114 patients (21%); however, when the ventriculographic data were also included, the issue was significant in only 64 patients (12%) (p < 0.001). Thus myocardial viability is an important issue in 21% of patients with CAD when conventional thallium imaging is used, but this percentage decreases to 12% when wall motion and ejection fraction data are also included. These data may be important in considerations for the need of metabolic imaging and emerging scintigraphic techniques. PMID- 1442504 TI - Cardiac manifestations of the antiphospholipid syndrome. AB - The antiphospholipid syndrome has been associated with multiple cardiac abnormalities. The earliest reports were of valvular disease, including verrucous endocarditis, as well as valvular thickening and insufficiency. Subsequently, antiphospholipid antibodies were implicated in coronary artery disease manifested by premature myocardial infarction and coronary artery bypass graft occlusion. In addition, there have been rare reports of intracardiac thrombi and diffuse cardiomyopathy in association with antiphospholipid antibodies. In this review, we discuss the nature and prevalence of the cardiac manifestations of the antiphospholipid antibody syndrome as well as some of the proposed pathophysiologic mechanisms. We also provide examples from our own experience. The expanding spectrum of cardiac disease associated with antiphospholipid antibodies suggests an important role for these antibodies in certain types of cardiac pathology. PMID- 1442505 TI - Ambulatory (Holter) electrocardiography signal-averaging: a current perspective. AB - Signal-averaging is an emerging new application of the ambulatory ECG. Whereas real-time signal-averaging of the high-resolution ECG has led to the measurement of abnormal QRS complex parameters and to the detection of ventricular late potentials in patients with a history of ventricular tachycardia or fibrillation at increased risk of an arrhythmic event, similar measurements can also be derived from ambulatory ECG tape recordings. This review describes the technical differences between real-time and ambulatory high-resolution ECG signal averaging, and the early clinical studies that correlated measured QRS complex parameters and defined the agreement of late potential detection with the two technologies. Although there appears to be a promising cost-effective benefit from ambulatory ECG signal-averaging, limitations imposed by the technical differences must be recognized, and additional investigation is needed to define the appropriate clinical use and criteria for best diagnostic and prognostic value. PMID- 1442506 TI - Role of perfluorochemical emulsions in the treatment of myocardial reperfusion injury. AB - Perfluorochemicals are substances with small particle size, low viscosity, and high oxygen-carrying capacity. The role of one perfluorochemical preparation. Fluosol, an emulsion of two perfluorocarbons, a detergent Pluronic F-68 (poloxamer 188), and phospholipids on myocardial reperfusion injury was investigated in a closed-chest canine model of regional ischemia. Intracoronary and intravenous infusions of Fluosol in the perireperfusion period significantly reduced infarct size and improved ventricular function in animals that were examined for up to 2 weeks after reperfusion. Fluosol preserved endothelial structure and endothelium-dependent relaxation of large and small vessels. Fluosol reduced neutrophil plugging of capillaries and attenuated neutrophil infiltration into the reperfused bed. Ex vivo studies of neutrophil function demonstrated apparent suppression of chemotaxis and lysozyme degranulation in cells from animals that were treated with Fluosol. However, treatment of cells in vitro manifested enhanced superoxide anion production within 5 minutes of incubation even with low concentrations of Fluosol. This effect was found to be almost entirely attributable to the detergent, Pluronic F-68. The stimulation of neutrophils by Fluosol was found to result directly from phagocytosis and indirectly from activation of the complement cascade. These findings suggest that perfluorochemicals may provide a novel form of therapy to enhance myocardial salvage after successful reperfusion. The mechanism appears to be due to stimulation and subsequent "deactivation" of neutrophils peripherally, which thereby reduces their cytotoxic potential in the reperfused myocardium. The role of the oxygen-carrying ability of the perfluorocarbons in the reduction of reperfusion injury remains to be determined. In a pilot study in human beings, Fluosol that was used as adjunctive therapy with angioplasty has also been shown to improve regional ventricular function. Clinical trials with perfluorochemical emulsions appear warranted to determine the role of reperfusion injury in limiting myocardial salvage in patients who are undergoing pharmacologic or mechanical reperfusion. PMID- 1442507 TI - Visualization of myocardial cellular architecture using acoustic microscopy. AB - The resolution of an ultrasound transducer depends on its frequency. The resolution improves when higher frequency transducers are used. A 1000 MHz transducer has a resolution of approximately 1 micron. Acoustic microscopy utilizes very high-frequency ultrasound (600 to 1000 MHz) to visualize structures on a microscopic level. Unstained, deparaffinized, 5 microns sections of myocardial biopsy specimens from 10 patients were placed on a slide and imaged using an Olympus UH3 scanning acoustic microscope. To compare with light microscopy, the section used for acoustic microscopy was subsequently stained with hematoxylin and eosin and a serial section from the paraffin block was stained with PTAH stain. Myocytes, myofibrils, and interstitial tissue were accurately imaged. Pathologic phenomena such as cell fallout, interstitial fibrosis, and lymphocytic infiltration were identified by acoustic microscopy. Intramural vessels, nuclei of endothelial cells, and the media were clearly identified by this technique. There was close correlation between findings by acoustic microscopy and light microscopy. Acoustic microscopy permitted the visualization of cardiac cellular detail with a resolution similar to that of light microscopy. Unlike light microscopy, acoustic microscopy requires no staining of the specimen. PMID- 1442508 TI - Guidance of directed coronary atherectomy by intracoronary ultrasound imaging. PMID- 1442509 TI - Reversal of silent myocardial ischemia by surgery for isolated anomalous origin of the left anterior descending coronary artery from the pulmonary artery. PMID- 1442510 TI - Percutaneous balloon angioplasty through an anomalous left main coronary artery. PMID- 1442511 TI - Myocardial imaging with technetium 99m sestamibi after exercise-induced ventricular tachycardia. PMID- 1442512 TI - Transient left ventricular dyskinesia as a consequence of myocardial stunning. PMID- 1442513 TI - Mycobacterium avium-intracellulare infection of an automatic implantable cardioverter defibrillator. PMID- 1442514 TI - Successful repair of a pseudoaneurysm originating from a true left ventricular aneurysm. PMID- 1442515 TI - Thallium-201 and gallium 67 single photon emission computed tomographic imaging in cardiac sarcoidosis. PMID- 1442516 TI - Balloon dilatation of primary infundibular stenosis of the right ventricular outflow tract. PMID- 1442517 TI - Diastolic murmur audible without a stethoscope and associated with aortic dissection in Marfan's syndrome. PMID- 1442518 TI - Unique manifestations of congenital coronary artery fistulas. PMID- 1442519 TI - Venous sheath to facilitate cardiac catheterization via the umbilical vein. PMID- 1442520 TI - Use of laryngoscope and esophageal stethoscope to visually direct intraoperative insertion of pediatric transesophageal echocardiographic probe in infants and small children. PMID- 1442521 TI - Transient ischemic attacks after long-term clamshell occluder implantation for closure of atrial septal defect. PMID- 1442522 TI - Pseudoaneurysm of a saphenous vein coronary artery bypass graft with a fistula draining into the right atrium. PMID- 1442523 TI - Exercise testing for stratifying cardiac risk following thrombolytic therapy for acute myocardial infarction. PMID- 1442524 TI - Counseling reduces dispensing accidents. PMID- 1442525 TI - Health care reform: to be or not to be? Part 2: Where are we heading? AB - The call for a new national health care system reflects the inability of the current system to provide access for all, control costs, and maintain quality. In Part 1 of this two-part series (September American Pharmacy, p. 28), the authors discussed the forces driving our current system. PMID- 1442526 TI - Major depression: its recognition and treatment. Part 1: First-generation antidepressants. PMID- 1442527 TI - Ofloxacin is not an antibiotic. PMID- 1442528 TI - DUE software highlights therapeutic issues. AB - Drug use evaluation (DUE) or drug use review (DUR) for the ambulatory care setting is creating many opportunities to improve the pharmaceutical care provided by pharmacists. This study documents one year of peer-review interventions based on a retrospective drug utilization review software system (Qualisure, Q-A, Inc.) that screens patient profiles for a high likelihood of drug therapy problems. Letters are written to physicians and pharmacists providing care to these patients. The software identifies frequent opportunities for selecting therapeutic class alternatives to prescribed agents. Antibiotics, antihistamines, nonsteroidal anti-inflammatory drugs, and antidepressants were the classes for which therapeutic class alternatives were most often recommended. PMID- 1442529 TI - Deborah Thorn: practicing 'academic detailing'. PMID- 1442530 TI - Fecal occult blood testing for colorectal cancer. PMID- 1442531 TI - Unclaimed prescriptions: an overlooked opportunity. AB - Unclaimed prescriptions are an overlooked component of medication noncompliance. Of 21 pharmacies surveyed for prescriptions unclaimed for 30 days or more, pharmacies averaged 21.4 prescriptions each (450 total), with the mean age of 45.6 days. More than 50% of unclaimed prescriptions were new phoned-in prescriptions. Anti-infective agents were the largest class of unclaimed medications, followed by analgesics and respiratory agents. Pharmacists can use unclaimed prescriptions as a basis for increasing their patient-oriented services. PMID- 1442532 TI - Characteristics of Louisiana dispensing physicians. PMID- 1442533 TI - A transition category of drugs: win-win-win-win? PMID- 1442534 TI - Common misconceptions about chronic pain. PMID- 1442535 TI - Counseling in special populations: the elderly patient. AB - This seventh installment in the series on value-added services provides pharmacists with a systematic approach to identifying and meeting the special counseling-related needs of the ambulatory elderly patient. The article describes the physical, mental, and social changes that characteristically accompany the aging process and that create special problems for pharmacists and their elderly patients during the delivery of pharmaceutical care. It also describes a systematic approach that pharmacists can use to evaluate whether their elderly patients need special counseling. Finally, it illustrates how the principles that are discussed can be applied in the practice setting. PMID- 1442536 TI - Purpose of medication will reduce errors. PMID- 1442537 TI - APhA secures pharmacists' right to compound. PMID- 1442538 TI - Treatment of acute diarrhea in children. PMID- 1442539 TI - The pharmacists officentre: providing quality care. PMID- 1442540 TI - OBRA '90 and your pharmacy computer system. PMID- 1442541 TI - Major depression: its recognition and treatment. Part 2. Second-generation and newer antidepressants. PMID- 1442542 TI - Taking the lead at APhA. PMID- 1442544 TI - Turning tragedy into opportunity. PMID- 1442543 TI - Interpreting digoxin concentrations. AB - In all cases, clinical assessment of the patient is the most critical factor in determining dose and interpreting concentrations. When done accurately, laboratory assessment of drug concentrations represents only one source of information. Serum concentrations must be taken into account along with all other relevant clinical data before one can arrive at appropriate management decisions. They must not be considered in isolation and out of context. If the laboratory report is at variance with your clinical judgment, "it will often be the better part of wisdom to question (or reject) the report." PMID- 1442546 TI - Is corporate sponsorship improper? PMID- 1442545 TI - Computer applications for marketing services, monitoring patients. PMID- 1442547 TI - 'Poison pill'. PMID- 1442548 TI - Amid grim projections, hope for an AIDS vaccine. PMID- 1442549 TI - Ask the Pharmacist. PMID- 1442550 TI - Ask the Pharmacist. PMID- 1442551 TI - Health care reform: to be or not to be? Part 1: The motivating forces. PMID- 1442552 TI - Biotechnology: an opportunity for pharmacists. PMID- 1442553 TI - Focus on women: Madison Pharmacy Associates. PMID- 1442554 TI - New federal DUR requirements for pharmacists in 1993. PMID- 1442555 TI - CQI: changing systems to improve quality. PMID- 1442556 TI - Choosing condoms. AB - Condoms for men are currently the most effective of the nonprescription contraceptive methods. They are readily available, simple to use, and relatively inexpensive, and they are not associated with major adverse effects. If used both properly and consistently, condoms can significantly reduce the risk of transmission of HIV and other STDs. The protection offered by the latex condom may be increased by the concurrent use of a vaginal foam or cream containing nonoxynol 9. The practicing pharmacist should know about the variety of condoms available, be able to explain their correct use to maximize effectiveness, and compare condom use with other types of contraceptives. The practitioner should be available to answer patrons' questions and provide counseling on contraceptives and "safe sex" practices. PMID- 1442557 TI - Update on the treatment of Alzheimer's disease. AB - The research and clinical experience of the past decade have provided a wealth of new knowledge about the causes of AD and the treatment of individuals afflicted with this progressive, irreversible illness. Public awareness of the costs of the disease has increased both at a national level and at a family and individual level. Despite these advances, the care and treatment of the AD patient are complex in that the risks of therapy often outweigh benefits. The pharmacists can play a key role by ensuring rational therapy, providing professional support to AD care givers, and serving as a source of information in both the ambulatory and institutional patient settings. PMID- 1442558 TI - EPA's role in worker protection. PMID- 1442559 TI - Lung cancer mortality among industrial workers exposed to formaldehyde: a Poisson regression analysis of the National Cancer Institute Study. AB - The Formaldehyde Institute (FI) sponsored additional Poisson regression analysis of lung cancer mortality data from the joint National Cancer Institute (NCI)/FI cohort study of workers exposed to formaldehyde to investigate the previously reported effects of plant and latency period and to assess the impact of short term workers (under 1 yr employment) on the results. There were 242 lung cancer deaths in this cohort of 20,067 white male workers. With OCMAP software, lung cancer death rates for the white males in this cohort were computed by plant, age, calendar time, and job type for several time-dependent formaldehyde exposures, including formaldehyde exposure in the presence of 12 selected co exposures: ammonia (AM), antioxidants (AN), asbestos (AS), carbon black (CB), dyes/inks/pigments (DY), hexamethylenetetramine (HX), melamine (ME), particulates (PT), phenol (PH), plasticizers (PL), urea/urea compounds (UR), wood dust (WD), and a composite co-exposure (X5) involving AN, HX, ME, PH, and UR.A 1.6-fold increase in lung cancer risk was found, beginning approximately 16-20 yr after first employment in the study plants with no evidence of a differential effect of latency between hourly and salaried workers or among the various categories of formaldehyde exposure as measured by cumulative average intensity or length of exposure. The statistically significant heterogeneity in lung cancer risk among the 10 plants could not be explained by interplant differences in cumulative or average intensity of exposure to formaldehyde, either without regard to co exposures or in the presence of any of the 12 co-exposures considered individually. Plant was not a statistically significant predictor of lung cancer risk when cumulative exposure to the composite X5 was included in the model, suggesting that some component of X5, or a correlate, could at least partly account for the overall heterogeneity. No significant associations were found for cumulative, average, or length of exposure to formaldehyde without regard to co exposure, but positive associations were found for cumulative exposure to formaldehyde in the presence of several co-exposures (AN, HX, ME, PH, and UR). For workers who were never exposed to any of 10 co-exposures associated with an increased lung cancer risk, there was a decreasing pattern of estimated lung cancer risk ratios relative to cumulative formaldehyde exposure. Similar patterns were seen when the analysis was restricted to the long-term workers. Analysis of the internal cohort rates corroborates previous analyses of NCI/FI cohort data in that significant positive associations were found between the risk of lung cancer and cumulative exposure to formaldehyde in the presence of several of the same co exposures. No such associations were found in the absence of these co-exposures. PMID- 1442560 TI - Assessment of multiple markers of environmental tobacco smoke (ETS) in controlled, steady-state atmospheres in a dynamic test chamber. AB - Controlled test atmospheres of sidestream and mixed mainstream/sidestream tobacco smoke were produced in a dynamic test chamber of 16.9 m3 volume. University of Kentucky 1R4F research cigarettes were automatically smoked by a Borgwaldt smoking machine. Different target levels of smoke were attained by varying the number of cigarettes being smoked (one or two cigarettes continuously) and dilution airflow through the chamber (1.6 to 7.4 m3/min). For each level, a "smoke index" was calculated as the number of cigarettes being smoked divided by the dilution flow rate. Ultraviolet light-absorbing particulate matter (UVPM); aerosol counts and size distribution; and concentrations of CO, NO2, NH3, formaldehyde, acetaldehyde, acrolein, and nicotine were determined in the test atmospheres and background dilution air. Parameters exhibiting the highest correlations with smoke index (r2 > 0.98) included UVPM, aerosol counts, formaldehyde, and acetaldehyde. The other parameters were also highly correlated with r2 > 0.9 in each case. Differences in concentration for sidestream and mixed mainstream/sidestream atmospheres were statistically significant for acetaldehyde, formaldehyde, and CO; in each case the level was higher in mixed mainstream/sidestream smoke. These results demonstrate the utility of employing multiple markers for assessment of environmental tobacco smoke levels and for dichotomizing the contributions of sidestream and mainstream smoke to these levels. The generation factors developed in this work can be used for estimating required ventilation rates for attainment of target air quality conditions in smoking rooms. PMID- 1442561 TI - Review of respirator performance testing in the workplace: issues and concerns. AB - Performance capability of respirators has traditionally been evaluated by testing components of the respirator (e.g., filter efficiency), facepiece fit, total inward leakage, or some other measure of performance evaluated under laboratory conditions. In recent years, increased emphasis has been placed on development of test methods suitable for evaluating respirator performance in the workplace. The goal of such testing is to evaluate the level of protection provided by respirators in the work environment. The AIHA Respiratory Protection Committee believes that workplace testing of respirators has the potential to be an excellent tool for increasing knowledge about the effectiveness of respiratory protection. However, a number of technical issues remain to be addressed before optimal test protocols and data analysis methods can be defined. The progress made to date in workplace testing will be reviewed, and broader discussion about key elements that must be considered when developing guidelines for testing respirators in the workplace will be initiated. PMID- 1442562 TI - Determination of program protection factors for half-mask respirators used at a mineral sands separation plant. AB - A study was conducted at a mineral sands separation plant to evaluate the workplace performance of half-mask filter cartridge respirators. Inhalation exposure was estimated by measuring the dust and radioactivity concentration inside the respirator while it was worn or hanging around the worker's neck. The program protection factor was determined by simultaneously measuring inside-mask and ambient (outside-mask) concentrations. A total of 27 tests were conducted, covering three brands of half-mask respirators; facial hair on test subjects ranged from clean-shaven to bearded. Program protection factors varied from 1.8 to 13 for dust exposure and 2.5 to 21 for radioactivity exposure. The geometric mean program protection factor over all tests was 5.1 (geometric standard deviation [GSD] = 1.7) for dust exposure and 7.5 (GSD = 1.7) for radioactivity exposure. A minimum program protection factor of 3.5 could be applied to ambient airborne concentration data to obtain a conservative, but more realistic, estimate of inhalation exposure on a worker category basis. PMID- 1442563 TI - Active noise control: a review of the field. AB - Active noise control (ANC) is the application of the principle of the superposition of waves to noise attenuation problems. Much progress has been made toward applying ANC to narrow-band, low-frequency noise in confined spaces. During this same period, the application of ANC to broad-band noise or noise in three-dimensional spaces has seen little progress because of the recent quantification of serious physical limitations, most importantly, noncausality, stability, spatial mismatch, and the infinite gain controller requirement. ANC employs superposition to induce destructive interference to affect the attenuation of noise. ANC was believed to utilize the mechanism of phase cancellation to achieve the desired attenuation. However, current literature points to other mechanisms that may be operating in ANC. Categories of ANC are one-dimensional field and duct noise, enclosed spaces and interior noise, noise in three-dimensional spaces, and personal hearing protection. Development of active noise control stems from potential advantages in cost, size, and effectiveness. There are two approaches to ANC. In the first, the original sound is processed and injected back into the sound field in antiphase. The second approach is to synthesize a cancelling waveform. ANC of turbulent flow in pipes and ducts is the largest area in the field. Much work into the actual mechanism involved and the causal versus noncausal aspects of system controllers has been done. Fan and propeller noise can be divided into two categories: noise generated directly as the blade passing tones and noise generated as a result of blade tip turbulence inducing vibration in structures. Three-dimensional spaces present a noise environment where physical limitations are magnified and the infinite gain controller requirement is confronted. Personal hearing protection has been shown to be best suited to the control of periodic, low-frequency noise. PMID- 1442564 TI - Health and safety implications of European community 1992 (EC92). Management committee. American Industrial Hygiene Association. AB - Progress toward the implementation of a single, common market in Europe is well underway. European-wide standards and regulations are being formulated to remove the physical, fiscal, and technical barriers to the free movement of goods, services, capital, and people among member states. In 1992, the target year for implementation, members of the European Community are attempting to harmonize their health and safety standards so that each nation is on equal footing. The European Community has given high priority to health and safety to the extent that 1992 has been declared the "year of health and safety in the workforce." The EC-rulemaking bodies have developed requirements for significant hazards, including risk communication and risk assessment. Efforts are underway to develop directives addressing exposure limits, product safety, and environmental protection. The result of this ambitious strategy will present substantial opportunities and challenges for the member countries, American companies with EC based subsidiaries, and any company that sells products in the European market. The end result could have a much farther reaching effect. To emphasize this, I will quote James Tye, president of the British Safety Council, who said, "The European Community will eventually be 700 to 800 million strong as other nations join it. I have no doubt it will be the dominant market in the world, assuredly as far as the field of health and safety is concerned. I also have no doubt that the standards we will be developing in the European Community will be followed by Japan and the United States. PMID- 1442565 TI - Assessment of intermittent trichloroethylene exposure in vapor degreasing. AB - To validate various sampling strategies in assessment of trichloroethylene (TCE) exposure, urine and air samples were obtained from 29 metal workers involved in vapor degreasing. Urinary trichloroacetic acid and trichloroethanol were useful metabolites to estimate TCE exposure on a group basis, but the predictive value of a single urine sample was low when related to the air concentration. With intermittent TCE exposure, the best information is obtained by analyzing both metabolites. PMID- 1442566 TI - Assessing viable myocardium with thallium-201. AB - Patients with chronic coronary artery disease and potentially reversible left ventricular dysfunction can often be successfully identified by one or more clinical indicators of myocardial viability, including regional wall motion, systolic wall thickening, regional myocardial perfusion as determined by perfusion tracers, and redistribution of thallium-201. In some patients, however, viable but "hibernating" myocardium will exist even when none of the above are evident. Myocardial viability in this situation can be detected with a high degree of accuracy by the demonstration of preserved metabolic activity by positron emission tomography (PET) scanning. Additionally, modifications of the standard exercise-redistribution thallium protocol may also produce accurate results. These modifications include late thallium-201 redistribution imaging, performed 8-72 hours following initial thallium injection, and thallium reinjection at rest after early (3-4 hours) or late (8-72 hours) redistribution imaging. These methods can identify viable myocardium in many thallium defects that appear to be irreversible on a standard 3-4 hour redistribution image. In addition, serial imaging after administration of thallium-201 at rest may also provide valuable insights into myocardial viability. These imaging modalities have important practical applications in the evaluation and management of patients with coronary artery disease and left ventricular dysfunction. PMID- 1442567 TI - Myocardial thallium-201 scintigraphy for assessment of viability in patients with severe left ventricular dysfunction. AB - Many patients with ischemic heart disease and depressed left ventricular (LV) function have asynergic zones with sustained microcirculatory perfusion and myocardial metabolic activity that exhibit improved systolic function after coronary revascularization. The 2 predominant noninvasive techniques used to determine myocardial viability in patients with severely depressed LV function are thallium-201 (201Tl) scintigraphy and positron emission tomography (PET). Myocardial extraction of 201Tl is unaltered under experimental conditions of myocardial stunning or short-term hibernation (characterized by decreased flow and ischemic dysfunction). Akinetic or dyskinetic LV wall segments can exhibit normal or near normal 201Tl uptake as long as some residual flow is present. 201Tl scintigraphy can identify viable asynergic segments when performed on patients with severe coronary artery disease who are in the resting state. Many of these patients have initial resting defects that demonstrate delayed redistribution, or mild persistent defects that show improved perfusion and function after revascularization. There is a direct correlation between the extent of 201Tl uptake in zones of severe regional myocardial asynergy and the magnitude of improvement in resting LV ejection fraction after coronary bypass surgery. Rest 201Tl scintigraphy may help in the selection of patients with coronary artery disease and severely depressed LV function who would benefit the most from revascularization. PMID- 1442568 TI - Prognostic value of thallium-201 myocardial perfusion imaging in three primary patient populations. AB - Knowledge of a patient's coronary anatomy alone is often insufficient to predict who will benefit from revascularization. Risk of cardiac events is related more to the presence of viable myocardium supplied by coronary arteries that are hemodynamically significant. Myocardial perfusion imaging with thallium-201 has been shown to reveal the presence and extent of jeopardized viable myocardium. In addition, thallium-201 imaging can demonstrate exercise-induced left ventricular dysfunction, manifested by increased thallium-201 myocardial imaging has important prognostic value in a wide spectrum of patients with coronary artery disease. The use of thallium-201 to predict cardiac events in patients with known or suspected coronary artery disease, in patients following myocardial infarction, and in patients undergoing noncardiac surgery is reviewed. PMID- 1442569 TI - Thallium-201 single-photon emission computed tomography (SPECT) in the assessment of coronary artery disease. AB - Of all currently available techniques, thallium-201 single-photon emission computed tomography (SPECT) is the most time-tested noninvasive method for the detection of coronary artery disease (CAD). Recent pooled data show an overall sensitivity of 90% and a specificity of 70% for thallium-201 SPECT. Of patients with single-vessel coronary disease, 83% are identified by SPECT. Nearly all patients with double- and triple-vessel coronary disease (93% and 95%, respectively) are also identified. Thallium-201 SPECT imaging is also very effective in diagnosing CAD imaging is also very effective in diagnosing CAD using pharmacologic stress testing. In certain patient populations (e.g., in sedentary patients or those using anti-ischemic medications), pharmacologic stress testing with dipyridamole or adenosine may be a logical alternative to exercise testing. Moreover, many patients have physical disabilities that preclude appropriate exercise testing. Intravenous adenosine is a very potent direct coronary vasodilator, with the advantage of an ultrashort half-life, which eliminates the need to administer an antagonist in the majority of patients. In addition, the dosage of adenosine can be adjusted during the infusion, if necessary. The importance of thallium-201 SPECT during exercise or pharmacologic vasodilation transcends diagnosis, since it also plays an important role in the prognostic evaluation of patients with stable angina or postmyocardial infarction. Risk evaluation can be done with submaximal exercise electrocardiographic testing, but there is evidence that the addition of perfusion scintigraphy enhances the ability to predict future risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442570 TI - Comparison of thallium-201 and technetium-99m methoxyisobutyl isonitrile. AB - Thallium-201 (201Tl) is a well-established radionuclide used in myocardial perfusion imaging for assessing the presence and prognostic significance of coronary artery disease. Recently, technetium-99m hexakis-2-methoxyisobutyl isonitrile (99mTc-sestamibi) has become available for the same diagnostic and prognostic procedures. This discussion compares the imaging characteristics and clinical applications of 201Tl with those of 99mTc-sestamibi. There is a strong diagnostic concordance between the 2 agents in symptomatic patients. Various comparative clinical trials have shown in numerous patients that both agents have a similar diagnostic yield in both planar and single-photon emission computed tomography (SPECT) imaging. Because of better image quality of the 99mTc agent, there is a trend toward better specificity and normalcy rate, in comparison to 201Tl. However, when using reinjection imaging protocols, 201Tl retains a unique place as an imaging agent to identify viable myocardium. PMID- 1442571 TI - Usefulness of ultrafast magnetic resonance imaging in healed myocardial infarction. AB - The value of ultrafast magnetic resonance imaging (MRI) in the assessment of dynamic contrast enhancement and myocardial perfusion abnormalities was evaluated in 20 patients with healed myocardial infarction, who also underwent 2 dimensional echocardiography. At baseline and after bolus injection of the paramagnetic contrast agent gadolinium-diethylenetriaminepentaacetic acid (DTPA) (0.04 mmol/kg body weight), single-level short-axis MRI was performed every third RR interval with an acquisition time of 500 ms. Myocardial signal intensities were measured in transmural myocardial regions of interest. After gadolinium-DTPA injection, infarcted and normal myocardium demonstrated a signal intensity enhancement of 50 and 134%, respectively (p < 0.001). A signal intensity of normal relative to infarcted myocardium increased from 1.25 +/- 0.22 (SD) before to 1.91 +/- 0.41 after gadolinium-DTPA (p < 0.001). The rate of signal increase in the infarcted and normal myocardium was 5.17 +/- 2.22 and 18.99 +/- 9.96 s-1 (p < 0.001), respectively. Ultrafast MRI using gadolinium-DTPA bolus administration clearly identifies myocardial perfusion abnormalities in patients with healed myocardial infarction. The infarct site on MRI corresponded with the location of wall motion asynergy determined by echocardiography. It is concluded that gadolinium-DTPA-enhanced ultrafast MRI provides noninvasive assessment of myocardial perfusion in patients with proven coronary artery disease. PMID- 1442572 TI - Placebo effect of nitrate monotherapy for myocardial ischemia. AB - Nitrate monotherapy was assessed by treadmill exercise stress testing in 18 patients with significant but relatively asymptomatic myocardial ischemia who were receiving no other antianginal therapy. In addition, prolonged ambulatory electrocardiographic monitoring was performed in 7 patients with demonstrable ischemia during baseline monitoring. After baseline assessment, 5 treatment periods were used in a random order (each of 1 week duration), incorporating 2 dose levels of transdermal nitrate (10 and 20 mg/24 hours) and isosorbide dinitrate (ISDN) (30 and 60 mg/day in divided doses) with a 10-hour nitrate-free interval every 24 hours, as well as a placebo period using a double-blind technique. All treatment periods (including placebo) showed a significant (p < 0.01) 45 to 69% prolongation in the time to 1 mm ST depression during exercise. Paired baseline times of 231 +/- 28 and 233 +/- 30 seconds increased to 367 +/- 37 seconds with 30 mg/day of ISDN, 393 +/- 37 seconds with 60 mg/day of ISDN, 381 +/- 31 seconds with 10 mg/day of transdermal nitrate, and 372 +/- 33 seconds with 20 mg/day of transdermal nitrate. The value for placebo was 342 +/- 29 seconds, which was not significantly different from active treatment (p > 0.1). Some patients appeared to individually respond to > or = 1 nitrate preparation significantly more than to placebo, but this appeared to be unpredictable and largely independent of dosage level and route of administration. There was a qualitatively similar but statistically insignificant reduction in total ischemic time during ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442573 TI - Prediction of late cardiac events by dipyridamole thallium imaging in patients undergoing elective vascular surgery. AB - Dipyridamole thallium scintigraphy has previously been shown to have prognostic value in the preoperative assessment of patients scheduled to undergo vascular surgery, but its effect on the long-term outcome is less well-defined. In the largest series to date, dipyridamole thallium scanning was performed in 360 patients before elective vascular surgery and survivors were followed for a mean of 31 months. In the 327 patients who underwent vascular surgery, operative death and nonfatal myocardial infarction occurred in 4.9 and 6.7%, respectively. A cardiac event (nonfatal myocardial infarction or cardiac death) occurred in 14.4% of patients with a transient thallium defect, as opposed to 1% with a normal scan (p < 0.001). Logistic regression analysis revealed that the best predictor of a perioperative event was the presence of a reversible thallium defect, elevating the risk by 4.3-fold. Late cardiac events occurred in 53 (15.2%) surgical survivors or nonsurgically treated patients. Patients with a fixed perfusion abnormality had a 24% late event rate, compared with 4.9% in those with a normal dipyridamole thallium study (p < 0.01). Cox analysis demonstrated that a fixed thallium defect was the strongest factor for predicting a late event and increased the relative risk by almost fivefold. A history of congestive heart failure was the only significant variable that contributed additional value to that of a fixed defect alone. Life-table analysis confirmed the strong relation of a fixed defect to cardiac event free survival (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442574 TI - Prognosis of patients with sustained ventricular tachycardia and of survivors of cardiac arrest not inducible by programmed stimulation. AB - The aim of this study was to analyze the long-term clinical outcome of 60 prospectively studied patients with documented sustained ventricular tachyarrhythmia that was not inducible during baseline programmed ventricular stimulation: 39 with cardiac arrest due to noninfarction ventricular fibrillation (VF) and 21 with mild hemodynamically compromising sustained ventricular tachycardia (VT). Left ventricular ejection fraction was 55 +/- 14% in the VF group and 50 +/- 13% in the VT group (difference not significant). Patients were discharged without conventional antiarrhythmic drugs and received only empirical beta-blocker therapy. During a mean follow-up period of 21 +/- 16 months (mean +/ SD), 10 of 60 patients (17%) died suddenly. The actuarial incidence of sudden death at 1 and 4 years was similar in both groups (VF group, 10 and 20%; VT group, 16 and 16%) (p = 0.48). The actuarial incidence of sudden cardiac death was significantly higher in patients with left ventricular ejection fraction < or = 40% than in those with > 40% (1-year incidence in VF group, 40 vs 0%; VT group, 50 vs 0%) (p = 0.005 and p = 0.01, respectively). Multivariate regression analysis identified left ventricular ejection fraction < or = 40% and previous myocardial infarction as the only independent predictor of sudden cardiac death. The occurrence of frequent ventricular pairs during Holter monitoring was the only independent predictor of sustained VT recurrences. It is concluded that patients with sustained ventricular tachyarrhythmia in whom arrhythmia was non inducible during baseline ventricular stimulation and not treated with antiarrhythmic therapy have a favorable outcome if left ventricular ejection fraction is high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442575 TI - Reproducibility of stress redistribution thallium-201 SPECT quantitative indexes of hypoperfused myocardium secondary to coronary artery disease. AB - To determine the reproducibility of quantitative indexes of hypoperfused myocardium by exercise thallium-201 single-photon emission computed tomography, duplicate studies were performed in 16 stable patients within 1 month. Twenty three other patients, with intervals up to 13 months between studies, were retrospectively identified from medical records. Symptoms, weight, heart rate achieved and peak systolic blood pressure during the 2 studies were similar. Maximal counts circumferential profiles' polar maps were generated and divided into 3 vascular territories. The hypoperfused myocardium was defined as the percent stress profile points below the normal level. The observed values were compared between the 2 studies for each patient. Defect size ranged from 0 to 73%. The concordance correlation coefficient (a measure of the closeness of the data points to the line of identity) and mean absolute deviation were 0.94 and 4.5%, respectively, when all patients were considered together, 0.93 and 3.2%, respectively in the reproducibility group, and 0.94 and 5.1%, respectively, in the retrospective group. Inter- and intraobserver reproducibility were also very high. For individual vessels, the concordance correlation coefficients were all > or = 0.89 and the mean absolute deviations between 3.7 and 9%. Thus, in stable patients with repeat thallium studies within a year, the percent hypoperfused myocardium is highly reproducible. PMID- 1442576 TI - Composition of atherosclerotic plaques in the epicardial coronary arteries in juvenile (type I) diabetes mellitus. AB - The composition of atherosclerotic plaques in 331 five-mm segments of the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries of 8 patients with juvenile (mean age at onset, 9 years; mean age at death, 29 years) diabetes mellitus was determined by computerized planimetric analysis. Analysis of all coronary segments disclosed that the plaques consisted primarily of dense (53%) and cellular (38%) fibrous tissue. Pultaceous debris (7%), foam cells (1.2%) and calcific deposits (0.7%) occupied a small percentage of the plaques. Thus, 91% of the coronary plaques in these young diabetic patients consisted of fibrous tissue and nearly all of the remaining 9% consisted of lipid deposits. Analysis of composition according to degrees of cross-sectional luminal narrowing revealed marked increases in dense fibrous tissue (from 31 to 74%), pultaceous debris (from 3 to 12%), and calcific deposits (from 0% to 3%) as the cross-sectional area narrowing increased from < or = 25% to > 75%. Compared with older patients with fatal coronary artery disease, the patients with juvenile diabetes had more dense fibrous tissue and pultaceous debris and less calcific deposits. PMID- 1442577 TI - Effects of infusion of L-arginine into the left anterior descending coronary artery on acetylcholine-induced vasoconstriction of human atheromatous coronary arteries. AB - Hypercholesterolemia and atherosclerosis are conditions associated with impaired endothelium-dependent relaxation. In hypercholesterolemic animals, intravenous administration of L-arginine, the precursor of nitric oxide, normalizes endothelium-dependent vasodilator activity. In the present study, we questioned whether intracoronary administration of L-arginine in patients with coronary artery disease could improve coronary vascular reactivity to acetylcholine. Thirteen hypercholesterolemic patients with diffuse coronary atherosclerosis but nonstenotic lesions of the left anterior descending (LAD) coronary artery were investigated. Quantitative coronary angiography and subselective intracoronary Doppler flow velocity measurements were performed to determine LAD diameters and coronary blood flow. Intracoronary infusion of acetylcholine was performed during 3 consecutive 3-minute periods at incremental rates adjusted to achieve estimated final concentrations of 5 x 10(-7), 10(-6) and 5 x 10(-6) M. After evaluation of the response to acetylcholine, L-arginine was infused into the LAD at the rate of 25 mg/min (10(-3) M) and the same stepwise 3-minute infusions of acetylcholine were repeated during infusion of L-arginine. Infusion of acetylcholine induced a dose-dependent reduction of distal epicardial LAD diameter reaching -48.5 +/- 17% at 5 x 10(-6) M (p < 0.01 vs control values). L-arginine alone had no effect on the distal LAD diameter but attenuated acetylcholine-induced vasoconstriction to 21 +/- 9% at 5 x 10(-6) M acetylcholine (p < 0.01). Coronary blood flow showed a biphasic response to acetylcholine, increasing by 41 +/- 12% at 5 x 10(-7) M (p < 0.01) and decreasing by 21 +/- 13% at 5 x 10(-6) M (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442578 TI - Prognosis with abnormal thallium images in the absence of significant coronary artery disease. AB - In the presence of coronary artery disease (CAD), thallium imaging has been reported to add prognostic information that is independent of coronary anatomy. To investigate the prognostic importance of thallium imaging in the absence of significant CAD, 87 patients (65 men, 22 women) with abnormal thallium images without significant CAD were followed for a median duration of 22 months (range 11 to 50). Tomographic thallium images obtained immediately and 4 hours after exercise were interpreted by 2 experienced observers who graded thallium uptake in 24 segments in 3 views (short axis, horizontal long axis, vertical long axis) on a 5-point scale (normal; mildly, moderately, or severely reduced; absent). All patients had an abnormal thallium study, defined as a reversible defect of at least mild severity or a fixed defect of at least moderate severity seen in > or = 2 views, or a combination of these, and a coronary angiogram with stenosis not > or = 70% in diameter narrowing. Eighty-two patients had at least 1 reversible segment, and 26 patients had defects in > or = 2 coronary artery distributions. During follow-up there were no deaths or myocardial infarctions. Coronary angioplasty and bypass surgery were performed in 2 patients. Three-year survival without myocardial infarction or revascularization was 97%. Patients with abnormal thallium images in the absence of significant CAD have an excellent short-term prognosis. PMID- 1442579 TI - Efficacy and tolerability of simvastatin and pravastatin in patients with primary hypercholesterolemia (multicountry comparative study). The European Study Group. AB - A total of 291 patients with primary hypercholesterolemia [total plasma cholesterol > or = 6.20 mmol/liter (> or = 240 mg/dl)] were enrolled in an open, randomized, parallel, comparative study of simvstatin and pravastatin. All patients started or continued a standard lipid-lowering diet for > or = 6 weeks before entry into the 4-week placebo baseline period. There were 145 patients who received simvastatin and 146 patients who received pravastatin, both at the commonly recommended starting dose of 10 mg once daily, for a treatment period of 6 weeks. Concentrations of total cholesterol in plasma were reduced by 23% with simvastatin, and by 16% with pravastatin. Concentrations of low-density lipoprotein cholesterol in plasma were reduced by 32 and 22%, and high-density lipoprotein cholesterol concentrations were increased by 7 and 5% with simvastatin and pravastatin, respectively. Plasma triglyceride concentrations were reduced by 13% with simvastatin and by 6% with pravastatin. Adverse experiences were similar between treatment groups and both drugs were well tolerated. In each treatment group, 3 patients were withdrawn from the study for clinical adverse experiences; 1 patient in the pravastatin group required a reduction in dose to 5 mg/day because of insomnia. At the commonly recommended starting dose for each, simvastatin had a significantly greater lipid-lowering effect than pravastatin. Both drugs were well tolerated. PMID- 1442580 TI - Frequency and implications of resetting and entrainment with right atrial stimulation in atrial flutter. AB - Thirty-three patients (24 with typical and 9 with atypical flutter-wave morphology) were studied to evaluate the incidence and implications of resetting and entrainment of atrial flutter with right atrial stimulation. Resetting with single extrastimulus was present in 23 cases (group A) and absent in 10 (group B). Most cases of reset flutter were typical (20 of 23). Fixed fusion indicative of entrainment was observed in all 29 cases with pacing trains. Groups A and B did not differ significantly in flutter cycle length (230 +/- 20 vs 223 +/- 19 ms), atrial functional refractory period (165 +/- 18 vs 167 +/- 22 ms) or longest paced cycle length producing entrainment (213 +/- 19 vs 210 +/- 19 ms). In contrast, the return cycle after the longest paced cycle length producing entrainment was significantly shorter in group A (228 +/- 27 vs 284 +/- 56 ms; p = 0.001). The return cycle in group A was virtually identical to the flutter cycle length, whereas in group B it was greater (p = 0.002 compared with group A). Resetting was more frequent in typical than atypical flutter (20 of 24 vs 3 of 9; p = 0.01). Both typical and atypical flutter can be transiently entrained by right atrial pacing. Lack of resetting and longer return cycle, suggesting a longer conduction time between the reentrant circuit and the stimulation site, were mostly observed in atypical flutter. The data suggest a different location for both types of flutter, and may have implications for ablation techniques. A more cautious approach, with more extensive mapping, appears appropriate for ablation attempts of atypical flutter. PMID- 1442581 TI - Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension. AB - The benefit of antihypertensive therapy in reducing cardiovascular morbidity and mortality associated with isolated systolic hypertension has now been established by the Systolic Hypertension in the Elderly Program. However, there is little information about the relative effectiveness of different drug regimens in this condition. This study compared the efficacy and tolerability of 50 mg of atenolol, 10 mg of enalapril, 25 mg of hydrochlorothiazide and 2.5 mg of isradipine in the treatment of isolated systolic hypertension. After a 3-week placebo run-in phase, 24 subjects were randomized into a 4-period double-blind crossover study by use of an orthogonal latin square design. Treatment periods were of 6 weeks' duration with titration to a higher dose after 4 weeks in those not reaching goal blood pressure (BP). Each active treatment was followed by a 3 week placebo washout. Casual clinic and 24-hour ambulatory BP (Accutracker II) were measured at the end of each treatment phase. Routine biochemistry was also performed after the placebo run-in, at the end of each active treatment phase, and after the placebo run-out. Of the 24 subjects entered (mean age 72.3 years, 38% men) 20 completed the whole study. Mean +/- standard deviation of supine clinic and daytime ambulatory BP on entry were 181/79 +/- 21/9 mm Hg and 165/82 +/- 23/15 mm Hg, respectively. All drugs reduced mean casual and ambulatory BP significantly relative to placebo but only hydrochlorothiazide and enalapril produced a consistent hypotensive effect throughout the entire 24-hour period. Isradipine and enalapril exhibited a relatively greater effect on reducing systolic BP than either hydrochlorothiazide or atenolol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442582 TI - Systemic hypertension associated with tricyclic antidepressant treatment in patients with panic disorder. AB - In a sample of 114 patients, 6 patients developed hypertension while taking tricyclic antidepressants. All these patients were diagnosed as having panic disorder, with or without major depression. Half of the 6 patients had a previous diagnosis of hypertension, which had been well controlled by antihypertensive drugs for years. A comparison group of patients with major depression, who had never had panic attacks, had no cases of hypertension induced by these antidepressants. These findings raise the possibility that patients who have panic disorder may experience cardiovascular disregulation that increases their risk for antidepressant-induced hypertension. PMID- 1442583 TI - Persistent hemodynamic improvement with short-term nitrate therapy in patients with chronic congestive heart failure already treated with captopril. AB - To evaluate the therapeutic potential of organic nitrates in patients with chronic congestive heart (CHF) failure already treated with angiotensin converting enzyme (ACE) inhibitors, the temporal hemodynamic effects of oral isosorbide dinitrate, 40 to 120 mg administered every 6 hours to 11 nitrate responders who had been treated with captopril 89 +/- 32 mg/day, were studied. The administration of isosorbide dinitrate resulted in a significant decline in mean right atrial pressure, from 13 +/- 6 mm Hg at baseline (mean value of measurements performed every 2 hours for 24 hours with captopril therapy) to 9 +/ 4 mm Hg at 1 hour with persistent effect for most of the study period. Mean pulmonary artery pressure decreased from 38 +/- 7 mm Hg at baseline to 29 +/- 9 mm Hg at 1 hour, with effect persisting for 24 hours. Mean pulmonary artery wedge pressure also decreased from 24 +/- 6 to 15 +/- 7 mm Hg at 1 hour and remained significantly reduced for 20 hours. Systemic blood pressure demonstrated a transient decrease lasting 2 hours after initiation of therapy which was asymptomatic in all patients. The results of this study demonstrate a preserved vasodilatory effect of organic nitrates in patients already treated with ACE inhibitors. Nitrates mediated improvement in right and left ventricular filling pressures, and reduction of pulmonary hypertension demonstrates a rationale for the use of these therapeutic methods in combination and suggest the need for long term evaluation of the effect of nitrate therapy in patients with chronic CHF already treated with ACE inhibitors. PMID- 1442584 TI - Impaired forearm vasodilation to hyperosmolal stimuli in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy. AB - Patients with congestive heart failure (CHF) have impaired peripheral vasodilation during exercise. Hyperosmolality is one local stimulus that produces vasodilation during exercise in normal subjects. This study addressed the hypothesis that vasodilation to hyperosmolal stimuli is impaired in patients with CHF. Forearm blood flow responses to intrabrachial artery infusions of isoosmolar (280 mosm/kg) and hyperosmolal (480 and 660 mosm/kg) solutions of saline and glucose were compared in 9 patients with CHF and 13 normal subjects. Forearm blood flow was measured by strain gauge plethysmography. In the normal subjects, hyperosmolal infusions of 480 and 660 mosm/kg increased forearm blood flow by 3.12 +/- 0.40 and 6.80 +/- 0.67 ml/min/100 ml forearm volume, respectively (both p < 0.001 compared with isoosmolal infusions). In contrast, in the patients with CHF, these infusions increased forearm blood flow by 2.19 +/- 0.44 and 4.06 +/- 0.92 ml/min/100 ml forearm volume (p < 0.05 normal vs CHF). The impaired forearm blood flow responses in heart failure occurred despite significantly greater (p < 0.05, normal vs CHF) increases in venous osmolality (17.3 +/- 6.5 vs 9.6 +/- 1.3 mosm/kg for the 660 mosm/kg infusion). There were no differences between groups in forearm venous hematocrit, calcium, and sodium or potassium changes during hyperosmolal infusions. It is concluded that peripheral vasodilation to hyperosmolal stimuli is impaired in patients with CHF. PMID- 1442585 TI - Long-term efficacy of physiologic dual-chamber pacing in the treatment of end stage idiopathic dilated cardiomyopathy. AB - The long-term efficacy of physiologic dual-chamber (DDD) pacing in the treatment of end-stage idiopathic dilated cardiomyopathy was evaluated in a longitudinal study of up to 5 years in 17 patients. The considerable clinical improvement achieved after implantation of a pacemaker programmed for DDD pacing at an atrioventricular delay of 100 ms was maintained throughout the follow-up period or until death and was associated with a consistent decrease in New York Heart Association class and an increase in left ventricular ejection fraction. Cardiothoracic ratio, heart rate and echocardiographic dimensions progressively decreased, and systolic and diastolic blood pressures increased. Median survival time was 22 months. During follow-up, 4 patients received donor hearts, 9 had a sudden death at home without defined cause or after a thromboembolic event, and 1 died from adenocarcinoma. Three patients survived the follow-up. No patient needed rehospitalization owing to a worsening of heart failure after pacemaker implantation. An interruption of pacing in DDD mode for 2 to 4 hours was followed within the first months by a marked decrease in left ventricular ejection fraction and an increase in cardiothoracic ratio and echocardiographic dimensions, but this response consistently decreased during follow-up. The data indicate that DDD pacing can be recommended as a useful tool in the long-term treatment of end-stage idiopathic dilated cardiomyopathy, with progressive improvement in cardiac function and a reduction of the dilatation of the left ventricle. PMID- 1442586 TI - Differences in direction-dependent shortening of the left ventricular wall in hypertrophic cardiomyopathy and in systemic hypertension. AB - To determine whether patients with hypertrophic cardiomyopathy (HC) have an altered mode of contraction of the left ventricular (LV) wall related to underlying myocardial abnormalities, geometric changes in the LV wall were analyzed at 2 points of the cardiac cycle (end-diastole and end-systole) using 2 dimensional echocardiography. The relations between meridional and circumferential shortening of the LV midwall, mean wall thickening, and the changes in the short-axis cross-sectional area of the LV wall at the level of chordae tendineae were determined in 18 patients with nonobstructive HC, and were compared with those in 31 normal subjects and 19 patients with essential systemic hypertension. In normal subjects, no significant difference was observed between meridional (16.3 +/- 2.4%) and circumferential (17.1 +/- 4.0%) shortening, whereas cross-sectional LV wall area increased significantly at end-systole (p < 0.001). In patients with hypertension, all measured indexes were not different from those in normal subjects. In contrast, patients with HC had significantly reduced meridional shortening (p < 0.001) and mean wall thickening (p < 0.01). Consequently, a striking difference was observed between meridional (8.9 +/- 2.4%) and circumferential (16.9 +/- 3.2%) shortening (p < 0.001). Furthermore, no increase in cross-sectional LV wall area was observed at end-systole. Thus, echocardiographic detection of direction-dependent contraction can be a useful index for distinguishing HC from systemic hypertension. PMID- 1442587 TI - Myocardial disarray at junction of ventricular septum and left and right ventricular free walls in hypertrophic cardiomyopathy. AB - The abnormality of the myocardium in hearts with hypertrophic cardiomyopathy (HC) was assessed regarding whether the muscle bundle in the mid-wall layer maintains its normal circular and continuous orientation surrounding the left ventricular (LV) cavity. Forty-seven autopsied hearts with HC were examined. The LV wall midway between the base and apex was divided into 6 segments in the transverse plane. Histologically, the circular orientation was destroyed largely or completely due to marked fascicle disarray in 77% of the anterior and posterior junctional segments. In 33% of the middle portion of the ventricular septum and in 34% of the anterior and posterior portions of the LV free wall, the midwall layer showed disarray of muscle fibers or small fascicles. In contrast, the lateral LV free wall was devoid of disarranged fibers in its midwall layer. Myocardial fibrosis usually was predominant in the portion where disarray was marked. There were deep tissue clefts often in the area of junction. In 11 hearts (7 from patients aged > 65 years), the circular unit was intact in almost every segment, as it was in 9 of 10 control hearts. The destruction of the circular unit in the area of septal-free wall junctions in most patients with HC is a previously undescribed morphologic feature of HC. This discontinuity may result from retention of an abnormal fetal myocardial architecture in which the septal latitudinal muscle was continuous with the right ventricular free wall. PMID- 1442588 TI - Intra- and interobserver reproducibility of Doppler-assessed indexes of left ventricular diastolic function in a population-based study (the Framingham Heart Study). AB - The reproducibility of a variety of Doppler indexes of diastolic function in an epidemiologic setting and in atrial fibrillation have not been reported. This study examined the reproducibility of left ventricular inflow in subjects in sinus rhythm (n = 80) and atrial fibrillation (n = 12), randomly selected from the original cohort of the Framingham Heart Study. The following Doppler indexes were assessed for all subjects: peak and integral of early (E) diastolic inflow velocity, acceleration slope and time, deceleration slope and time, and pressure half-time. For subjects in sinus rhythm, the following parameters also were measured: the peak and integral of late (A) diastolic inflow velocity, ratios of peak velocities and integrals E/A, and atrial filling fraction. Intraobserver and interobserver variability were evaluated by statistical methods including Student's t test of the systematic differences (bias), percent bias, correlation coefficients, measurement precision, and percent precision. In subjects in sinus rhythm, although the interobserver bias was statistically significant for most of the parameters, it was < 10% for all but 1 parameter (acceleration time). For the peak and integral measures, the intra- and interobserver correlations were > or = 0.89, with intra- and interobserver percent precision measures within 2.2 to 13.0% of the corresponding mean values. The acceleration, deceleration and pressure half-time measures had somewhat lower correlations (interobserver correlations ranging from 0.59 to 0.96), with percent precision measures further from the corresponding means (interobserver percent precision ranging from 10.1 to 19.5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442589 TI - Effect of omega-3 fatty acids on the vascular response to angiotensin in normotensive men. AB - There is a widespread interest in fish oil as a dietary supplement and possible nonpharmacologic adjunct in the treatment of hypertension. The effect of dietary fish oil on blood pressure is controversial and the effect on systemic hemodynamics and regional vascular reactivity in humans is unknown. To address these questions, a double-blind, placebo-controlled, crossover study on the effect of dietary fish oil substitution was performed during a carefully controlled diet in 8 normotensive men. Systemic hemodynamics and the forearm vascular response to intrabrachial artery infusions of norepinephrine, phentolamine and angiotensin II were obtained. Compared with a safflower oil placebo, dietary fish oil had no effect on cardiac output (6.42 +/- 0.38 vs 6.87 +/- 0.28 liters/min, p = not significant) or 24-hour blood pressure (122/68 +/- 3/3 vs 122/68 +/- 3/2 mm Hg, p = not significant). The vascular response to norepinephrine and phentolamine was unchanged. Fish oil, however, significantly (p < 0.05) reduced forearm vascular resistance responses to angiotensin II. These changes were associated with a reduction in plasma triglycerides (64 +/- 9 vs 39 +/- 4 mg/dl, p = 0.02) and an increase in plasma eicosapentaenoic acid levels (0.51 +/- 0.25 vs 1.72 +/- 0.35 microM, p < 0.05). Substitution of a moderate dose of fish oil for fat in a "Western diet" selectively attenuates the vascular response to angiotensin independently of changes in alpha-adrenergic vasoconstriction or systemic hemodynamics. PMID- 1442590 TI - Comparison of Doppler and two-dimensional echocardiography for assessment of pericardial effusion. AB - Respiratory changes in left ventricular inflow velocities by Doppler echocardiography have been used to assess cardiac tamponade; however, Doppler echocardiography has not been compared to right atrial or right ventricular collapse. Pulsed Doppler echocardiography of left ventricular inflow velocities was performed with respiratory monitoring in 28 patients with small to large pericardial effusions. Ten of the 17 patients (59%) with large effusions had equalization of right-sided diastolic pressures before pericardial drainage. The measurements performed included percent change in left ventricular inflow peak early velocity, isovolumic relaxation time, change in inferior vena cava diameter from apnea to inspiration, and the presence of right atrial and right ventricular collapse. Percent change in early left ventricular inflow velocities significantly correlated with pericardial effusion size (p = 0.001) and right ventricular collapse (p = 0.007), and showed a trend with right atrial collapse (p = 0.10). Pericardial effusions with a left ventricular inflow velocity change > 22% were found to have right-sided equalization at a 95% confidence interval. Our data indicate that the respiratory changes in Doppler echocardiographic parameters are useful in the assessment of pericardial effusion and tamponade. This study concurs with the hypothesis that there is a continuum of hemodynamic compromise in pericardial effusion that is easily detected by Doppler echocardiography. PMID- 1442591 TI - Shock-wave thrombus ablation, a new method for noninvasive mechanical thrombolysis. AB - Successful experimental and clinical experience with thrombus ablation has been attained with high-power acoustic energy delivered in a catheter. The goal of this study was to investigate the feasibility of noninvasive thrombus ablation by focused high-power acoustic energy. The source for high-power acoustic energy was a shock-wave generator in a water tank equipped with an acoustic lens with a fixed focal point at 22.5 cm. Thrombus was prepared in vitro, weighed (0.24 +/- 0.08 g), and inserted in excised human femoral artery segments. The arterial segments wer ligated, positioned at the focal point and then randomized into either test (n = 8) or control (n = 7). An x-ray system verified the 3 dimensional positioning of the arterial segment at the focal point. A 5 MHz ultrasound imaging system continuously visualized the arterial segment at the focal point before, during and after each experiment. The test segments were exposed to shock waves (1,000 shocks/24 kv). The arterial segment content was then flushed and the residual thrombus weighed. The arterial segment and thrombus were fixed and submitted to histologic examination. The test group achieved a significant ablation of thrombus mass (0.25 +/- 0.15 vs 0.07 +/- 0.003 g; p = 0.0001) after application of shock waves. Arterial segments showed no gross or microscopic damage. Ultrasound imaging revealed a localized (1.9 +/- 0.5 cm2), transient (744 +/- 733 ms), cavitation field at the focal point at the time of application of focused shock waves. Thus, focused high-power acoustic energy can effect noninvasive thrombus ablation without apparent damage to the arterial wall.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442592 TI - Role of transesophageal echocardiography in evaluation of pulmonary venous obstruction by paracardiac neoplastic masses. AB - From 71 consecutive patients with paracardiac neoplastic masses who underwent transesophageal echocardiography (TEE), obstruction of individual right upper pulmonary venous flow by compression by contiguous mass was detected by TEE in 4 patients before and disappeared after anti-neoplastic treatments. Pulmonary vein, contiguous neoplastic mass and their relation could be clearly visualized and assessed by TEE. Pulmonary venous obstruction was assessed as moderate degree by combination of Doppler flow characteristics and diameter of pulmonary vein. Before therapy, peak velocities and time-velocity integrals in obstructed right upper pulmonary venous flow were increased, whereas deceleration times of systolic flow were prolonged. After therapy, peak velocities and time-velocity integrals were reduced and deceleration times of systolic flow were shortened, with normalization of the diameter of the right upper pulmonary veins. Thus, TEE may be used to detect and evaluate pulmonary venous obstruction by neoplastic masses and its changes after antineoplastic treatments. PMID- 1442593 TI - Analysis of fractional area change at various levels in the normal left ventricle. PMID- 1442594 TI - Scarring of the left ventricular papillary muscles in sickle-cell disease. PMID- 1442595 TI - Limitations in the assessment of changes of cardiac output by Doppler echocardiography under various hemodynamic conditions. PMID- 1442596 TI - Abnormal electrocardiograms and cardiovascular risk: role of silent myocardial ischemia. Evidence from MRFIT. AB - The Multiple Risk Factor Intervention Trial (MRFIT) was designed as a primary prevention study to test the effect of multifactorial intervention on long-term outcome in men with a combination of risk factors that placed them in the top 10 15 percentiles of risk for coronary artery disease. Of the 12,866 patients in this study, the 3,600 men (about 28%) with abnormalities in the baseline electrocardiogram were prospectively identified. They were expected to be at increased risk for coronary events compared with those without electrocardiographic abnormalities. Analysis of cumulative mortality data following antihypertensive regimens that included high dosages of diuretics revealed an association between electrocardiographic abnormalities at rest and diuretic treatment that related to adverse outcome. When the dosages of the diuretic were lowered, this trend was reversed. It is proposed that diuretic related hypokalemia may predispose patients who may have silent myocardial ischemia to potentially fatal arrhythmias and that use of potassium-sparing antihypertensive regimens be considered in high-risk hypertensive patients. PMID- 1442597 TI - Role of myocardial oxygen demand in the pathogenesis of silent ischemia during daily life. AB - The role of myocardial oxygen demand in the pathogenesis of silent ambulatory myocardial ischemia was evaluated by reviewing and assessing the methods and results of recent studies. The performance of simultaneous ambulatory electrocardiographic and blood pressure monitoring in 25 men with proven coronary artery disease (CAD) revealed significant increases in heart rate and blood pressure (p < 0.001) preceding most silent ischemic events. By plotting the mean heart rate obtained at 5-minute intervals during the 30 minutes before an ischemic event, the ischemic heart rate was shown to be significantly higher (95 +/- 15 vs 74 +/- 11 beats per minute [bpm]; p < 0.01) than the nonischemic heart rate. The evaluation of heart rate changes during ambulatory ischemia (in patients with CAD and ischemia induced by an exercise test using gradual work load increments) showed a significant heart rate increase (> 10 bpm) at 1-5 minutes preceding the onset of ST-segment depression. Heart rate increases during exercise testing according to the gradual work load increments of the National Institutes of Health protocol were compared with the heart rate preceding ischemic events during daily life monitored by ambulatory electrocardiography and were found to be closely related. In contrast, heart rate increases that occurred during exercise testing using the standard Bruce protocol were higher and correlated less with those preceding ischemia in daily life. Heart rate and blood pressure increased significantly in most silent ischemic episodes, indicating that increased myocardial oxygen demand plays a significant role in the pathogenesis of myocardial ischemia during daily life. PMID- 1442598 TI - Use of intracoronary ultrasonography in assessing pharmacotherapy for myocardial ischemia. AB - Intracoronary ultrasonography can provide morphologic and physiologic information on coronary vasomotor responses to pharmacotherapy. Preliminary studies indicate a high correlation between dimensions determined by 2-dimensional echocardiography, angiography, and pathology. Similarly, the emerging data on intracoronary Doppler flow velocity responses beyond atherosclerotic obstructions before, during, and after coronary balloon occlusion will provide further insights into myocardial oxygen supply and its responses to pharmacotherapy during controlled myocardial ischemia. PMID- 1442599 TI - Relation between systemic hypertension and pain perception. AB - To test the hypothesis that hypertension diminishes pain perception, a study was made that evaluated the relation between arterial blood pressure and thermal pain perception in human subjects. The average mean arterial pressure in all 20 men studied (10 hypertensive, 10 normotensive) proved to be significantly related to both thermal pain threshold (p = 0.05) and tolerance (p = 0.003). The difference between normotensive and hypertensive groups in baseline and posttest plasma levels of beta endorphin was also significant (p = 0.02) and indicated an interaction between endogenous opioids and blood pressure. Other recent studies of hypertension in relation to hypalgesia were also reviewed. An increased pain threshold was found in hypertensive versus normotensive rats. In cats, electrical stimulation of vagal afferent nerves (cardiopulmonary baroreceptors) suppresses nociceptive responses, and both pharmacologic elevation of blood pressure and vascular volume expansion produce antinociception. Together with preliminary findings in human studies, these results indicate an interaction between pain controlling and cardiovascular regulatory functions that is probably mediated by the baroreceptor system. PMID- 1442600 TI - Significance of silent myocardial ischemia after coronary artery bypass surgery. AB - The prevalence and prognostic significance of transient myocardial ischemia after coronary artery bypass grafting (CABG) were evaluated. In 3 studies, ischemia was found in an average of 24% of patients by ambulatory electrocardiographic monitoring at 3-12 months after CABG. An average of 36% of patients in 3 other studies experienced ischemic ST-segment depression during exercise testing at 4 50 months after CABG. Of the ischemic episodes, 77% were silent during exercise testing. In the Coronary Artery Surgery Study (CASS) randomized patient subsets, survival at 12 years was significantly lower for patients who had either silent or symptomatic ischemia during exercise testing at 6 months after CABG compared with those who had no ischemia. PMID- 1442601 TI - The Council for Myocardial Ischemia and Infarction: advisory group reports on silent myocardial ischemia, heart rate control, and post-myocardial infarction management. PMID- 1442602 TI - Diagnostic and therapeutic implications: exploration through case discussions. PMID- 1442603 TI - Cardiac allograft arteriopathy: an ischemic burden of a different sort. AB - As heart transplant recipients live longer, an accelerated and distinct form of coronary artery disease develops that adversely affects survival. Indeed, cardiac allograft arteriopathy may be detected in as many as 90% of heart transplant recipients after 5 years. The precise incidence is not easily determined because the disease can be difficult to recognize when noninvasive tests are used; even angiography has substantive limitations. The distinct characteristics of this type of coronary artery disease result in a different form of chronic ischemic syndrome. The angiographic hallmark of allograft arteriopathy is an extensive, diffuse, obliterative process that primarily involves distal, small, subendocardial arteries. Endothelial injury seems to trigger the disease process. The arteriopathy is likely immunologically mediated and promoted or exacerbated by traditional atherosclerotic disease risk factors. Viral infection may be involved as well. To gain a better understanding of allograft arteriopathy, it is worthwhile to review its incidence, pathophysiology, prognosis, prevention, and treatment. PMID- 1442604 TI - Comparison of composition of atherosclerotic plaques in saphenous veins used as aortocoronary bypass conduits with plaques in native coronary arteries in the same men. AB - This study describes quantitatively the components of atherosclerotic plaques in saphenous vein grafts used for aortocoronary bypass and compares the findings with the plaques in the native coronary arteries in the same men. A total of 607 five-mm segments of saphenous veins and 797 five-mm segments of native coronary arteries were examined by computerized planimetric technique in 19 men, aged 39 to 82 years (mean 61), who had survived bypass operation for > 1 year. Comparison of the mean percentages of the plaque components in saphenous vein grafts in place for 14 to 26 months with those of the native coronary arteries revealed significant differences: cellular fibrous tissue, 86 vs 7%; dense fibrous tissue, 13 vs 82%; p < 0.05. As survival time after the bypass operation increased, composition of the plaques in the saphenous veins changed so that by approximately 80 months the amounts of cellular and dense fibrous tissue in both saphenous vein grafts and native coronary arteries were similar: 10 vs 16%, and 75 vs 71%; p = not significant. Thus, by about 7 years after a coronary bypass operation the composition of plaques in saphenous vein grafts is similar to that in the native coronary arteries of the same patients. PMID- 1442605 TI - Markedly increased periprocedure mortality of cardiac catheterization in patients with severe narrowing of the left main coronary artery. AB - In early reports, coronary arteriography in patients with left main (LM) coronary artery disease (CAD) had a substantial risk, but recent reports suggest that arteriography in these subjects is now associated with a low mortality. The present study was performed to examine the periprocedure mortality in patients with LMCAD undergoing catheterization, to compare the periprocedure mortality in these patients with that in subjects with less CAD and to identify the variables associated with pericatheterization mortality in this patient cohort. Of 4,009 patients undergoing elective coronary arteriography from 1978 to 1992, 176 had LMCAD. Of the 10 deaths during or within 24 hours of catheterization, 5 occurred in these 176 subjects. This periprocedure mortality of 2.8% in patients with LMCAD was > 20 times that of those without LMCAD (0.13%). In comparison with the 171 patients with LMCAD who survived, the 5 who died were older (67 +/- 8 vs 58 +/- 12 years), and had more severe LMCAD (92 +/- 10% vs 72 +/- 16%) and a lower cardiac index (1.9 +/- 0.4 vs 2.6 +/- 0.7 liters/min/m2) (p < 0.05 for all 3 variables). Thus, even in the 1980s and early 1990s, patients with LMCAD have a high pericatheterization mortality, especially those who are older and have severe LMCAD. PMID- 1442606 TI - Importance of early and complete reperfusion to achieve myocardial salvage after thrombolysis in acute myocardial infarction. AB - The importance of the timing and completeness of coronary artery reperfusion for limitation of acute myocardial infarction (AMI) size after intravenous thrombolytic therapy was studied in 39 patients. All had electrocardiographic epicardial injury and acute coronary angiography performed < 8 hours after symptom onset. Acutely jeopardized myocardium was estimated at baseline, and before and after angiography by quantitative ST-segment analysis. The AMI size was estimated on the final electrocardiogram by the Selvester QRS score. Left ventricular ejection fraction was measured at the time of acute angiography and before discharge in 31 of these patients. In the 21 patients with normal flow (Thrombolysis in Myocardial Infarction [TIMI] trial grade 3) in the infarct related artery, the amount of jeopardized myocardium decreased from baseline to that before and after angiography (17 to 11 and 11%, respectively; p < 0.00005), and the median final AMI size was reduced (17 to 9%; p = 0.0004). In 6 patients with suboptimal flow (TIMI grade 2), the median amount of jeopardized myocardium decreased slightly from baseline to that before to after angiography (15 to 12%); however, the median final AMI size was not reduced (17%). In 12 patients with no reperfusion (TIMI 0 to 1) flow, the median amount of jeopardized myocardium remained unchanged from baseline to that before angiography (21%), and the final AMI size was not significantly reduced. There was a significant inverse correlation between the change in global left ventricular function and the difference between electrocardiographic estimated jeopardized and final AMI size (rs = -0.53; p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442607 TI - Early and late changes in left ventricular filling after acute myocardial infarction and the effect of infarct size. AB - To characterize the early (1 week) and late (6 weeks) changes in left ventricular (LV) filling pattern associated with acute myocardial infarction (AMI) 45 patients (mean age 65 +/- 2 years) were studied by Doppler echocardiography. Based on clinical criteria, patients were divided into those with large (group L; n = 12) and those with small (group S; n = 33) infarcts and then compared with 16 age-matched control subjects. The following parameters were calculated from the mitral velocity waveform: (1) peak early and peak atrial velocities and their integrals; (2) peak early to atrial velocity ratio and velocity integral ratio; and (3) the pressure half-time of the early wave. One week after AMI, group L showed a decreased atrial and increased early velocity, velocity ratio and integral ratio, whereas the pressure half-time of the early wave was shorter than that in group S and in control subjects. At 6 weeks group L showed a reduction in early velocity, early to atrial velocity ratio and integral ratio, whereas pressure half-time increased. When groups S and L were combined there was a good inverse correlation between pressure half-time and infarct size as measured by peak enzyme release (r = -0.64, p < 0.001). These data suggest that, depending on infarct size, patients exhibit a "restrictive" filling pattern early after the acute event. This is manifested by the greater proportion of filling occurring in early diastole, reflecting an overall increase in chamber stiffness. At 6 weeks, this pattern is less pronounced presumably due to the remodeling process. PMID- 1442608 TI - Dose and test for dipyridamole infusion and cardiac imaging early after uncomplicated acute myocardial infarction. AB - To evaluate the relation of the dose of intravenous dipyridamole on results of thallium and echocardiographic testing, the results of standard- (0.56 mg/kg/4 minutes) versus high- (0.84 mg/kg/10 minutes) dose dipyridamole were obtained 9 +/- 3 days after uncomplicated acute myocardial infarction in 57 patients. New wall motion abnormalities were compared with redistribution of thallium imaging and results of discharge coronary angiography. The sensitivity of thallium in predicting the presence of multivessel coronary artery disease was significantly (p < 0.01) higher (85%) than echocardiography (53%) and was unaffected by the dose. However the sensitivity of echocardiography was better with the higher dose (53 vs 14%). Minor adverse effects occurred in 34 patients (59%) after receiving the high dose and only in 4 patients (7%) after the standard dose (p < 0.001). Thus, thallium-201 scintigraphy during standard-dose dipyridamole infusion is more effective than high-dose dipyridamole echocardiographic testing in safely identifying patients who could benefit from early invasive evaluation and therapy. PMID- 1442609 TI - Exercise-induced S-wave prolongation in left anterior descending coronary artery stenosis. AB - Myocardial ischemia may decrease conduction velocity and produce QRS prolongation in the surface electrocardiogram. In cases with normal intraventricular conduction, areas of the myocardium contributing to the development of the S wave receive blood from all 3 major coronary arteries, whereas in left anterior hemiblock or right bundle branch block, most of the blood supply to the areas of the myocardium contributing to the development of the S wave is from the left anterior descending (LAD) coronary artery. To test the hypothesis that the S wave will be prolonged with exercise only in patients with LAD coronary artery stenosis and left anterior hemiblock or right bundle branch block, 88 patients with normal intraventricular conduction, 66 with left anterior hemiblock and 36 with right bundle branch block were studied. Sixty-four, 32 and 21 patients had LAD, right and left circumflex coronary artery stenoses, respectively. In patients with normal coronary arteries, S-wave duration decreased with exercise regardless of the status of ventricular conduction. In patients with coronary artery disease and normal intraventricular conduction, the S wave was prolonged slightly with exercise, but in those with left anterior hemiblock and right bundle branch block, it was prolonged significantly (12.5 +/- 6 and 10.4 ms, respectively) only in those with LAD, but not in those with circumflex or right coronary artery stenosis. S-wave prolongation in patients with LAD coronary artery stenosis and left anterior hemiblock or right bundle branch block most likely is related to exercise-induced ischemia in the areas of the myocardium contributing to the development of the S wave. PMID- 1442610 TI - Psychological, behavioral and biochemical risk factors for coronary artery disease among American and Italian male corporate managers. AB - Differences in psychological, behavioral and biochemical risk factors for coronary artery disease (CAD) among male corporate managers of 2 countries (United States and Italy), with very different age-specific rates of mortality for CAD were evaluated. In all, 129 American (mean age 43 +/- 7 years) and 80 Italian (mean age 45 +/- 7 years) managers volunteered to participate in this study. Each subject was administered several questionnaires assessing various psychological and behavioral risk factors for CAD, and all 129 Americans and 55 of 80 Italians had their blood drawn between 8:00 and 9:30 AM after overnight fasting for the measurement of plasma levels of dehydroepiandrosterone-sulfate (DHEA-S), total cholesterol, triglycerides, and apolipoproteins A-I and B. Italian managers reported significantly more cynicism and hostility, and less enjoyment in leisure activities than did American ones. Furthermore, 40 Italian (51%) and only 18 American (14%) managers were smokers (this difference being statistically significant). Although no significant differences were found in factors positively related with CAD (cholesterol, triglycerides and apolipoprotein B), there were clear differences in parameters inversely correlated with the incidence of CAD. Italian managers had significantly lower levels of plasma DHEA-S and apolipoprotein A-I than did American ones. In conclusion, this study found that Italian managers had a significantly more unhealthy psychological and behavioral profile than did American ones, and had lower levels of those biochemical parameters (apolipoprotein A-I and DHEA-S) thought to have a protective role against development of CAD. PMID- 1442611 TI - Diagonal earlobe crease as a marker of the presence and extent of coronary atherosclerosis. AB - This study evaluates the association between the presence of diagonal earlobe creases (ELC) and coronary artery disease (CAD). One thousand four hundred twenty four patients (760 men and 664 women, aged 30 to 80 years) were examined for the presence of ELC and classified into 2 groups: group I control--1,086 consecutive patients who denied symptoms of myocardial ischemia and were admitted to a general hospital for other reasons; group II CAD--338 patients with documented CAD (presence of > or = 70% coronary diameter stenosis at angiography). ELC was present in 304 patients (28%) in group I and 220 (65%) in group II (p < 0.0001). The patients were stratified in age groups to isolate the influence of age because the prevalence of ELC and CAD increased with advancing age (p < 0.0001 for both). This association remained statistically significant in all decades, except for patients aged > 70 years. To further remove the confounding effect of different age and sex distributions between the groups, a direct adjustment of the ELC prevalence was performed. When adjusted for age and sex, the prevalence of creases was still 58% higher in patients with CAD than in control subjects (p < 0.001). The presence of ELC was also related to the extent of CAD as measured by the number of major arteries narrowed (p = 0.015). The observed sensitivity of the sign for the diagnosis of CAD was 65%, the specificity 72%, the positive predictive value 42% and the negative predictive value 87%. PMID- 1442612 TI - Significance of noninvasive diagnostic techniques in patients with long QT syndrome. AB - The idiopathic long QT syndrome (LQTS) is an infrequently occurring disorder. Affected patients may have electrocardiographic alterations and are prone to syncope and sudden arrhythmogenic cardiac death. Adequate therapy may improve the prognosis of affected patients significantly. Therefore the early and precise diagnosis of LQTS has major prognostic impact. This study reports the diagnostic significance of standard electrocardiographic techniques and autonomic maneuvers in 14 patients with LQTS. The findings are compared with those of 14 healthy age matched control persons. QTc duration was significantly longer in patients with LQTS during standard 12-lead electrocardiography (489 +/- 56 vs 412 +/- 30 ms, p < 0.005), exercise stress testing (490 +/- 38 vs 409 +/- 18 ms, p < 0.001), cold pressor testing (512 +/- 45 vs 407 +/- 19 ms, p < 0.001), Valsalva maneuver (497 +/- 49 vs 407 +/- 19 ms, p < 0.001), minimal heart rate during 24-hours of ambulatory electrocardiographic recording (482 +/- 69 vs 402 +/- 22 ms, p < 0.01) and maximal heart rate during Holter monitoring (460 +/- 47 vs 411 +/- 27 ms, p < 0.005). Four of 14 patients with LQTS had pathologic findings during ambulatory electrocardiographic monitoring (2 patients with short episodes of torsades de pointes tachyarrhythmia, 1 patient with intermittent sinoatrial block, and 1 patient with intermittent TU-wave alterations), whereas all control persons had normal ambulatory electrocardiographic recordings (p < 0.05). Thus, noninvasive standard electrocardiographic techniques in combination with autonomic maneuvers may contribute significant information for a precise diagnosis in patients with suspected LQTS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442613 TI - Negative dromotropism of adenosine under beta-adrenergic stimulation with isoproterenol. AB - Adenosine depresses atrioventricular (AV) nodal function by binding to specific A1 receptors which activate the acetylcholine, adenosine-regulated potassium current. In addition, adenosine can act to antagonize the effects of beta adrenergic stimulation on AV nodal function. To assess the negative dromotropic effects of adenosine under beta-adrenergic stimulation, 15 patients were studied during clinical electrophysiologic study. During high right atrial pacing at a cycle length of 400 to 600 ms, adenosine was injected intravenously at an initial dose of 0.5 mg followed by a stepwise increment of 0.5 or 1.0 mg given at 5 minute intervals until a maximal dose of 12 mg was achieved or AV block developed. Intravenous isoproterenol (1 to 3 micrograms/min) was then infused to accelerate sinus rate by 20 to 30% during which intravenous injection of incremental doses of adenosine as described was repeated. The AV nodal conduction time (AH interval) was measured at each dose of adenosine. Dose-response curves of AV nodal conduction time (expressed as percent increase in AH interval) were studied during the control state and during isoproterenol infusion. The dose of adenosine required to produce AV nodal Wenckebach block, the increase in the AH interval by 50% (ED50) and the maximal response (Emax) were 3.4 +/- 0.9 mg, 1.8 +/- 0.9 mg and 60 +/- 4%, respectively, in the control state, and 3.7 +/- 0.8 mg, 2.0 +/- 0.7 mg and 56 +/- 4%, respectively, during isoproterenol infusion. No significant changes in ED50, Emax and the dose of adenosine yielding AV nodal Wenckebach block could be demonstrated between the control state and during isoproterenol infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442614 TI - Effects of the class III antiarrhythmic drug dofetilide on ventricular monophasic action potential duration and QT interval dispersion in stable angina pectoris. AB - The effects of intravenous dofetilide on ventricular monophasic action potential duration and effective refractory period at the right ventricular apex and outflow tract were studied in 18 patients (aged 37 to 70 years) with ischemic heart disease. Six patients received low-dose dofetilide as a 3 micrograms/kg loading dose over 15 minutes and a 1.5 micrograms/kg maintenance dose over 45 minutes; 6 received high-dose dofetilide 6 + 3 micrograms/kg and 6 placebo. During atrial pacing at a cycle length of 800 ms high-dose dofetilide prolonged right ventricular apex monophasic action potential duration by 45 ms (16%) and the effective refractory period by 40 ms (16%). At the right ventricular outflow tract, monophasic action potential duration was prolonged by 45 ms (15%) and effective refractory period by 55 ms (21%). During atrial pacing at a cycle length of 500 ms high-dose dofetilide prolonged the right ventricular apex monophasic action potential duration by 40 ms (18%) and the effective refractory period by 43 ms (21%). The right ventricular outflow tract monophasic action potential duration was prolonged by 33 ms (14%) and effective refractory period by 45 ms (21%). Dofetilide produced no increase in the dispersion of repolarization between the 2 sites. During the maintenance infusion QTc prolongation by high-dose dofetilide averaged 43 ms (10%) with no increase of interlead QT dispersion. The effects of dofetilide on QT interval and effective refractory period are shown to be due to a direct effect on action potential duration with no effect on dispersion. No rate dependence of monophasic action potential prolongation was detected at these cycle lengths. PMID- 1442615 TI - Catheter ablation of the atrioventricular junction using radiofrequency energy and a bilateral cardiac approach. AB - Radiofrequency current catheter ablation was used successfully to create complete atrioventricular (AV) block in 60 of 61 patients (98%) with drug refractory supraventricular tachyarrhythmias. The remaining patient developed Mobitz I AV block and is clinically improved (clinical efficacy 100%). In 54 patients (89%), complete AV block was achieved using a right-sided approach. Patients aged > 60 years needed significantly fewer right-sided radiofrequency applications to produce complete AV block (5.3 +/- 5.3 vs 11.1 +/- 10.0; p = 0.009). In 6 of 7 patients with unsuccessful right-sided ablation, a left ventricular approach was used. In each case, 1 to 4 additional radiofrequency applications produced complete AV block. Patients with unsuccessful right-sided ablation were generally younger than those with successful ablation (50 +/- 16 vs 64 +/- 11; p = 0.007). It is concluded that catheter ablation using radiofrequency current is an extremely effective means of producing complete AV block. Older patients appear to be more susceptible to right-sided radiofrequency approaches. Left ventricular ablation easily produces complete AV block in patients refractory to right-sided attempts. PMID- 1442616 TI - Long-term results of percutaneous mitral valvuloplasty with the Inoue balloon catheter. AB - The initial 85 patients who successfully underwent percutaneous mitral valvuloplasty (PMV) with the Inoue balloon catheter at the Guangdong Cardiovascular Institute between November 1985 and November 1988 had a mean follow-up period of 5 +/- 1 year (range 43 to 79 months). Before and after PMV and at follow-up, mean diastolic mitral gradients by the catheter method were 17.5 +/- 6.2, 3.1 +/- 3.3 and 3.3 +/- 3.4 mm Hg, respectively (p < 0.001 before vs after PMV and before vs follow-up; and p > 0.05 after PMV vs follow-up). Mean diastolic mitral gradients by the Doppler method were 18 +/- 6, 8 +/- 5 and 9 +/- 5 mm Hg, respectively (p < 0.001 before vs after PMV and before vs follow-up; and p > 0.05 after PMV vs follow-up). Mean diastolic mitral gradients by the Doppler method were 18 +/- 6, 8 +/- 5 and 9 +/- 5 mm Hg, respectively (p < 0.001 before vs after PMV and before vs follow-up; and p > 0.05 after PMV vs follow-up). Mitral valve areas by the echo-Doppler method were 1.1 +/- 0.3, 2.0 +/- 0.4 and 1.8 +/- 0.5 cm2, respectively (p < 0.001 before vs after PMV and before vs follow up; and p > 0.05 after PMV vs follow-up). Phonocardiographic and vectorcardiographic studies, and cardiopulmonary exercise testing showed significant improvement after PMV and at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442617 TI - A comparison of hospital and community-acquired infective endocarditis. AB - The epidemiology, clinical features, microbiology and outcome of 30 episodes of nosocomial endocarditis occurring over a 13-year period were reviewed and compared with 148 cases of community-acquired endocarditis. Twenty-eight patients (93%) had been in hospital for > 1 week and 10 patients (33%) for > 1 month when they developed endocarditis. Left-sided infection was most frequent; only 3 cases involved the tricuspid valve. Compared with community-acquired infection, patients tended to be older, had a greater incidence of congestive cardiac failure (p = 0.001) or hypotension (p = 0.0008) at presentation and were more likely to have bacteremia after an invasive procedure (83 vs 31%; p < 0.00001). Intravascular devices were the presumed source of bacteremia in 11 cases (37%); the same organism was isolated from both the blood and the suspected source of infection. Staphylococcus aureus was the most frequent causative organism, accounting for 17 episodes (57%), including 4 (13%) due to methicillin-resistant strains. Nosocomial endocarditis had a significantly higher mortality than did community-acquired infection (40 vs 18%; p = 0.02). Eight patients (27%) needed valve replacement. Proper adherence to protocols for management of intravascular devices and appropriate antimicrobial prophylaxis before procedures may have prevented endocarditis in 15 of 30 patients. PMID- 1442618 TI - Active infective endocarditis observed in an Indian hospital 1981-1991. AB - Clinical data from 186 patients (133 males and 53 females) with 190 episodes of infective endocarditis (IE) occurring between January 1981 and July 1991 were studied retrospectively at a large referral hospital in Northern India with the intention of highlighting certain essential differences from those reported in the West. The mean age was much lower (25 +/- SD 12 years, range 2 to 75 years). Rheumatic heart disease was the most frequent underlying heart lesion accounting for 79 patients (42%). This was followed by congenital heart disease in 62 (33%) and normal valve endocarditis in 17 (9%). Twenty-four patients had either aortic regurgitation (n = 15) or mitral regurgitation (n = 9) of uncertain etiology. Prosthetic valve infection and mitral valve prolapse were present in only 2 patients each. A definite predisposing factor could be identified in only 28 patients (15%). Postabortal sepsis and sepsis related to childbirth accounted for 6 and 5 cases, respectively. Only 1 patient had history of intravenous drug abuse. Two-dimensional echocardiography showed vegetations in 121 patients (64%). Blood cultures were positive in only 87 (47%), with a total of 90 microbial isolates. Commonest infecting organisms were staphylococci (37 cases) and streptococci (34 cases). Except for a significantly higher number of patients with neurologic complications in the culture-negative group, there were no differences between patients with culture-positive and culture-negative IE. Of the 190 episodes of IE, the patients had received antibiotics before admission in 110 (58%) instances. A significantly greater number of culture-negative patients had received antibiotics than did culture-positive patients (87 vs 23, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442619 TI - Cardiac dimensions determined by cross-sectional echocardiography in the normal human fetus from 18 weeks to term. AB - Assessment of cardiac dimensions of the chambers, great arteries and veins in the human fetus is important to distinguish abnormal dimensions from normal. This study establishes normal values based on cross-sectional echocardiographic measurements over the gestational period where these measurements may be clinically useful. Ventricular and atrial dimensions were measured from the 4 chamber view, the short-axis dimension immediately below the mitral and tricuspid valve leaflets in diastole, and the long axis from the closed apposed atrioventricular valves to their respective apices. The ventricular walls and septum were measured at the level at which cavity dimensions in diastole were measured, defining both the left and right ventricular wall thickness, as well as that of the ventricular septum. Furthermore, the long axis of the right and left atria was measured from the center of the apposed atrioventricular valve leaflets to the posterior atrial wall, and the sizes of the atrial chambers were defined using their widths at the prospective broadest points through the area of foramen ovale. From a variety of views, diameters were measured at maximal expansion of the main, left and right pulmonary arteries, the ductus arteriosus, and the superior and inferior venae cavae. The data were evaluated longitudinally from 18 weeks to term, and regression analysis was performed using the best fit of a linear or polynomial equation. The data provide a means for evaluating the normal sizes and dimensions of the fetal heart chambers, as well as the thickness of the ventricular walls and septum. PMID- 1442620 TI - Value of transesophageal echocardiography combined with computed tomography for assessing repaired type A aortic dissection. AB - Thirty-two patients with repaired type A aortic dissection were examined by transthoracic echocardiography (TTE) (n = 32), transesophageal echocardiography (TEE) (n = 30), computed tomography (CT) (n = 29), or a combination of all 3, to assess course and complications as a function of the surgical procedure. The mean follow-up period was 55.7 months (range 3 to 132). Surgery consisted of a replacement of the ascending aorta in 25 patients (group 1) with extension to the transverse aorta in 7 (group 2). The transverse diameter of the aorta, the persistence of the false lumen, thrombus formation and flow dynamics in the false lumen were evaluated by TEE. Ten patients (31%) had a dilation in the initial ascending aorta (sinus of Valsalva aneurysm in 6 patients, and a false aneurysm in the other 4). Three of 4 patients with a proximal pseudoaneurysm underwent operation after TEE and CT evaluation. In the descending thoracic aorta, there was good agreement between TEE and CT scan determinations of transverse vessel diameter. Persistence of flow within the false lumen was significantly more frequent in patients with a dilated aorta (p < 0.05), whereas thrombosis was seen more often and false lumen less often in patients with nondilated aorta. No significant differences in vessel status or outcome were observed between the 2 groups, although this may have been due to the small size of group 2. TEE is thus a well-tolerated method for postoperative follow-up of type A aortic dissection whatever the type of surgery. For the upper ascending aorta, CT provided sufficient data. PMID- 1442621 TI - Effectiveness and safety of bolus administration of alteplase in massive pulmonary embolism. AB - Animal studies have demonstrated that thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is accelerated and that bleeding is reduced when rt PA is infused over a short period. Previous clinical studies in patients with venous thromboembolism have shown that rt-PA is an effective thrombolytic agent when administered by continuous infusion over 2 to 24 hours. Clinical experience of bolus rt-PA administration in patients with massive acute pulmonary embolism (PE) is, however, limited. A prospective open study was conducted in which 54 patients with massive PE (Miller index > or = 20 of 34) received a 10-minute infusion of rt-PA at a dose of 1 mg/kg. Perfusion lung scanning was used to assess the change in pulmonary perfusion after drug administration. At 48 hours and 10 days, the mean absolute improvements in the perfusion defect were 11 and 31%, respectively. In addition, a significant clinical improvement occurred within 2 hours in 11 of the 15 shocked patients. Five patients died (9%) as a result of persistent shock (3 patients), neurologic damage (1 patient) or intracranial bleeding (1 patient). Major bleeding occurred in 8 patients (15%). Long-term follow-up information was available for 44 of the 49 discharged patients: 2 had died and 12 (27%) complained of persistent exertional dyspnea, 7 of whom had an associated heart or lung disease or chronic thromboembolism at admission. These results suggest that a bolus regimen of rt-PA could provide a convenient approach to thrombolytic therapy in patients with massive PE.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442622 TI - Course of left ventricular hypertrophy and function in end-stage renal disease after renal transplantation. AB - Cardiovascular complications are frequent and related to left ventricular (LV) hypertrophy and dysfunction in end-stage renal disease. To examine cardiac changes after renal transplantation, 24 hemodialysis patients (18 men and 6 women, age 47 +/- 12 years) were analyzed in a prospective follow-up study with echocardiography immediately before and 41 +/- 30 months after renal transplantation. Mean systolic blood pressure (hemodialysis vs transplantation: 156 +/- 35 vs 144 +/- 15 mm Hg; p = not significant [NS]), as averages of 6 measurements from 2 weeks, remained constant and elevated. The most frequent echocardiographic findings at both assessments were left atrial dilatation (75 vs 79%; p = NS) and LV hypertrophy (71 vs 67%; p = NS). After transplantation, an increase was found in mean left atrial diameter (41 +/- 5 to 44 +/- 5 mm; p < 0.05) and end-diastolic LV diameter (50 +/- 5 to 53 +/- 5 mm; p < 0.05) at constant LV muscle mass (332 +/- 104 vs 329 +/- 94 g; p = NS). LV ejection fraction (58 +/- 10% to 63 +/- 12%; p < 0.02) and stroke volume (98 +/- 26 to 118 +/- 25 ml; p < 0.02) improved. No influence of blood pressure in sporadic morning determinations or of dialysis fistula patency on alterations of LV mass or function was found. Left atrial diameters increased in patients with patent dialysis fistulas (41 +/- 7 to 45 +/- 5 mm; p < 0.05), but not in those with occluded fistulas (41 +/- 7 vs 42 +/- 4 mm; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442623 TI - What is the optimum dose of dipyridamole for cardiac imaging? PMID- 1442624 TI - Effect of a number of coronary arteries significantly narrowed and status of intraventricular conduction on exercise-induced QRS prolongation in coronary artery disease. PMID- 1442625 TI - Operative results after unsuccessful radiofrequency ablation for Wolff-Parkinson White syndrome. PMID- 1442626 TI - A prototype coronary electrode catheter for intracoronary electrogram recording. PMID- 1442627 TI - Effects of acute exposure to altitude (3,460 m) on blood pressure response to dynamic and isometric exercise in men with systemic hypertension. PMID- 1442628 TI - Spontaneous echocardiographic contrast with the carbomedics mitral valve prosthesis. PMID- 1442629 TI - Frequency of left atrial thrombi by transesophageal echocardiography in idiopathic and in ischemic dilated cardiomyopathy. PMID- 1442630 TI - Plasma levels of atrial natriuretic peptide in hypertrophic cardiomyopathy. PMID- 1442631 TI - Supravalvular aortic stenosis after replacement of the ascending aorta. PMID- 1442632 TI - Profound "pacemaker syndrome" in hypertrophic cardiomyopathy. PMID- 1442633 TI - Acronyms of major cardiologic trials. PMID- 1442634 TI - A grading index of serum lipid abnormalities. PMID- 1442635 TI - Hypnotherapy for warts (verruca vulgaris): 41 consecutive cases with 33 cures. AB - Published, controlled studies of the use of hypnosis to cure warts are confined to using direct suggestion in hypnosis (DSIH), with cure rates of 27% to 55%. Prepubertal children respond to DSIH almost without exception, but adults often do not. Clinically, many adults who fail to respond to DSIH will heal with individual hypnoanalytic techniques that cannot be tested against controls. By using hypnoanalysis on those who failed to respond to DSIH, 33 of 41 (80%) consecutive patients were cured, two were lost to follow-up, and six did not respond to treatment. Self-hypnosis was not used. Several illustrative cases are presented. PMID- 1442636 TI - Performance enhancement in physical medicine and rehabilitation. AB - Performance enhancement or mental practice is the "symbolic rehearsal of a physical activity without any gross muscular movements" to facilitate skill acquisition and to increase performance in the production of that physical activity. Performance-enhancement interventions have been well known in the area of sports psychology and medicine. However, clinical applications in physical medicine and rehabilitation have not flourished to the same extent, though the demand for improved physical performance and the acquisition of various motor skills are as important. In this paper I will describe how hypnosis can potentiate mental practice, present a model of mental practice to enhance performance, and describe how to help patients access an ideal performance state of consciousness. PMID- 1442637 TI - The dialogue technique of hypnotic induction. AB - In this paper we describe a technique of hypnotic induction, using a dialogue between two hypnotists. It combines, in principle, the utilization of the patient's unconscious resources (utilization principle) and verbal confusion (confusion principle) to evoke hypnotic responses. The process of the trance induction in the dialogue technique comprises four major stages: (1) preinduction verbal set, (2) unconscious access and utilization, (3) trance ratification and deepening, and (4) trance termination. Clinical experience suggests that the dialogue technique can "mask" the effect of confusion and produce trance states "spontaneously" for patients. Following the theoretical and methodological description of the technique, we also discuss appropriate clinical applications and a case example using the dialogue technique. PMID- 1442638 TI - Suggested posthypnotic amnesia in psychiatric patients and normals. AB - The present study examined both quantitative and qualitative hypnotizability differences among four psychiatric patient groups (dissociative disorder (n = 17), schizophrenic (n = 13), mood disorder (n = 14), and anxiety disorder (n = 14) patients), and normals (college students (n = 63). Dissociative disorder patients earned significantly higher corrected total scores on the Stanford Hypnotic Susceptibility Scale, Form C (mean = 7.94), than all other groups. Likewise, dissociative disorder patients initially recalled significantly fewer items when the posthypnotic amnesia suggestion was in effect (mean = .41) and reversed significantly more items when the suggestion was canceled (mean = 3.82) than all other groups. In contrast, schizophrenic patients recalled significantly fewer items when the amnesia suggestion was in effect (mean = 1.85) and reversed significantly fewer items when it was canceled (mean = .77) than the remaining groups. This qualitative difference between schizophrenic patients and the other groups on the suggested posthypnotic amnesia item was observed even though there were no significant quantitative differences between groups in overall hypnotic responsivity. PMID- 1442639 TI - Hypnotic age regression in an experimental and clinical context. AB - The aim of the present study was to investigate the role of a clinical context in the experience of hypnotic age regression. Twenty-five patients experienced hypnotic age regression in an experimental and clinical context in counterbalanced order. Patients obtained significantly lower scores for experimental age regression than for clinical age regression, in particular when the experimental assessment preceded the clinical assessment of age regression. Moreover, scores for clinical and experimental age regression were only significantly and positively correlated when the clinical assessment of age regression preceded the experimental assessment. These findings give a tentative indication that more patients are able to experience clinical age regression than can be predicted from their responses to an experimental suggestion for hypnotic age regression where almost no opportunities for patient contact or maximizing of hypnotic responsiveness are provided. PMID- 1442640 TI - The psychophysiological investigation of multiple personality disorder: review and update. AB - In 1984 Putnam reviewed the literature on the psychophysiological investigation of multiple personality disorder (MPD). Since his review, a large number of studies have been conducted and reported in the literature and at professional conferences. Currently, psychophysiologic differences reported in the literature include changes in cerebral electrical activity, cerebral blood flow, galvanic skin response, skin temperature, event-related potentials, neuroendocrine profiles, thyroid function, response to medication, perception, visual functioning, visual evoked potentials, and in voice, posture, and motor behavior. We review the new research on the psychophysiological investigation of MPD from published, unpublished, and ongoing studies, and we attempt to place current findings into a conceptual framework. We have noted findings from unpublished and ongoing studies, and, perhaps unfortunately, they represent a large amount of the data presently available. We conclude with a critical analysis of current research methodology and suggestions for future research. PMID- 1442641 TI - Self-hypnosis and computer monitoring in the management of obesity. PMID- 1442642 TI - Hypnosis and weight reduction: which is the cart and which is the horse? AB - Hypnosis has often been described as a useful adjunctive treatment for excess weight. However, the literature shows that very few controlled studies have been conducted in this realm, and none have incorporated the key variables of either the hypnosis components or the weight-reduction components. In this paper I offer a brief review of the literature on hypnosis for weight reduction, present weight reduction outcome data, outline variables common to people with chronic weight problems, and I offer suggestions for future uses of hypnosis within a comprehensive approach to weight reduction rather than as the primary treatment. Suggestions are also made concerning the multiple opportunities for future research using hypnosis in the substance-abuse field. PMID- 1442643 TI - Hypnotizability and recovery from cardiac surgery. AB - We studied 32 coronary bypass patients to examine the effect of hypnosis on recovery from surgery. The patients were assessed for hypnotizability with the Hypnotic Induction Profile (HIP) and assigned to experimental groups with a random stratification procedure to equate for differences in hypnotizability, age, and severity of illness. We taught patients in groups one and two formal hypnosis with different treatment strategies; patients in group three were not taught formal hypnosis or a treatment strategy. Scores on the HIP were significant predictors of recovery, independent of experimental treatment with formal hypnosis. Patients who scored "Midrange" stabilized more quickly in the intensive care unit (ICU) than those who scored "High" or "Low" (p = < .05). Patients who scored "High" had more labile blood pressure in the ICU compared to the "Midrange" and "Lows" (p = < .05). Measured hypnotizability was associated with the recovery sequence from surgery. PMID- 1442644 TI - Pseudomemory and age regression: an exploratory study. AB - Hypnotizable (N = 9) and simulating subjects (N = 8) were age regressed to the previous week's hypnosis session and received a suggestion to hear a phone ring during the earlier session (no phone actually rang). Pseudomemory rates in response to open-ended questions were low in this study (0% hypnotizable and simulating subjects) and in previous research (Lynn, Weekes, & Milano, 1989; 12.5% hypnotizable; 10% simulating subjects) in which the phone-ring suggestion was not embedded in the context of age regression. In response to a forced-choice question, 22.22% of the hypnotizable and 25% of the simulating subjects indicated that the suggested phone ring was an actual event, a pseudomemory rate somewhat higher than our previous study in which none of the subjects reported pseudomemories in response to a forced-choice question. When the occurrence of the target stimulus of a pseudomemory suggestion is publicly verifiable, the pseudomemory rate is low. PMID- 1442645 TI - The effect of prior knowledge of hypnotic items on hypnotic performance and depth. AB - First we exposed experimental subjects to either the hypnotic items they were about to experience or to those items embedded in a longer list of hypnotic items. We then asked them to give item-difficulty ratings prior to administration of a standard group susceptibility scale. Controls received no prior exposure to any hypnotic items. We obtained four dependent measures: hypnotic susceptibility score, an in-hypnosis depth report, Field (1965) Depth Inventory score, and retrospective depth reports. The three groups did not differ significantly on any of the dependent measures. Although this result differs from that of Shor, Pistole, Easton, and Kihlstrom (1984), who found that prior knowledge of items depressed susceptibility scores, this may be due to procedural differences between the two studies. Subjects' self-predictions of item difficulty were poor to modest, and accuracy of predictions was not related to any of the four dependent measures. PMID- 1442646 TI - Construct validity of the Dissociative Experiences Scale: II. Its relationship to hypnotizability. AB - Undergraduates (n = 311) who volunteered to participate in an experiment on "Hypnotizability and Personality" filled out several personality questionnaires (including the Dissociative Experiences Scale; DES), were administered the Harvard Group Scale of Hypnotic Susceptibility (HGSHS), and completed a self rating of hypnotizability. The DES overall score correlated significantly with the HGSHS summary score (r(309) = .12, p < .05, two-tailed) and with subject's self-rating of hypnotizability (r(309) = .13, p < .05, two-tailed). The magnitude of these correlations was similar to that observed in a previous study (.14 & .18) and is also similar in magnitude to the correlations typically observed between the HGSHS and the Tellegen Absorption Scale. The potential clinical implications of these findings are discussed. PMID- 1442647 TI - "Back from the future": a powerful age-progression technique. AB - This paper briefly reviews the benefits of using age-progression techniques in hypnotherapy, followed by a detailed explanation and illustration of the "back from-the-future" technique with two case examples, including their outcome. The patients presented with feelings of helplessness, hopelessness, and a sense of futurelessness. Following the hypnotherapeutic intervention, patients were instructed to take time to reflect on the session and to write down the specific experiences they had on their voyage into the future focusing on their visual images, auditory sensations, experiences with other senses (touch, smell, and taste), as well as thoughts, emotions, and self-perceptions. Follow-up validated that the patients maintained their therapeutic accomplishments several months after the initial interventions. PMID- 1442648 TI - The use of hypnotic age progressions as interventions with acute psychosomatic conditions. AB - Patients with the physical manifestations and physiological disturbances engendered by serious psychosomatic conditions often present with special needs in therapy. On a conscious level, these patients may have pessimistic views of the future, including the specter of imminent death, which, for some, is a real possibility. In this paper we review four clinical cases in which hypnotic age progressions reveal the patients' deepest positive hopes for survival and serve as ego-strengthening, integrating, and prognostic tools in the face of ominous symptoms of physical distress. PMID- 1442649 TI - The use of hypnotic age progressions as prognostic, ego-strengthening, and integrating techniques. AB - Age progression as a hypnotherapeutic technique is mentioned infrequently in the literature when compared with its counterpart, age regression. In this paper we explore the use of progressions, or "views of the future," as prognostic indicators of therapeutic progress and as valuable tools for ego strengthening and for the integration of clinical material. Age progressions vary in the types of suggestions given and can be used to promote growth on multiple levels, facilitating treatment goals and deepening the working-through process. We present six cases in which we used different types of age progressions, and we discuss the significance of the progressions used in each case, within the context of relevant clinical material. We conclude from our observations that the use of hypnotic progressions can be a sustaining, valuable aspect of hypnotherapy, particularly in providing an index of the current direction and progression of the therapy process itself. PMID- 1442650 TI - Protein metabolism and growth of term infants in response to a reduced-protein, 40:60 whey: casein formula with added tryptophan. AB - The effects of an experimental reduced-protein (13 g/L), milk-based formula with a whey-casein ratio of 40:60 and added tryptophan (Trp) (490 mumol/L, or 100 mg/L; EF) were measured by growth and protein biochemistry in term infants from 0 to 12 wk postnatally. Newborn infants (n = 95) were randomly assigned to receive EF or conventional formula (15 g protein/L, whey-casein ratio of 60:40; CF) and compared with 58 breast-fed infants (BF). Growth velocity for weight, length, and head circumference was similar between groups. In 79 infants, blood was sampled preprandially at 4, 8, and 12 wk. For all times, plasma Trp was similar in BF and EF infants (58.4 +/- 10.4 vs 59.5 +/- 14.7 mumol/L, mean +/- SD) but lower in CF infants (53.4 +/- 8.4, P < 0.05). The plasma Trp-large neutral amino acid (AA) ratio was higher with EF than with CF, as was prealbumin (P < 0.05). Formula-fed infants had higher (P < 0.05) plasma urea, prealbumin, total essential AA, branched-chain AA, and threonine than did BF infants. A reduced-protein formula with added Trp resulted in Trp status similar to that in BF infants, without compromising growth or protein biochemistry compared with CF infants. PMID- 1442651 TI - Growth patterns of breast-fed infants in affluent (United States) and poor (Peru) communities: implications for timing of complementary feeding. AB - We compared growth, dietary intake, and morbidity of infants breast-fed for > or = 12 mo from two populations: Davis, CA (n = 46) and Huascar, Peru (n = 52). When compared against WHO reference data (based primarily on formula-fed infants), Huascar infants appeared to falter as early as 3-4 mo, but when compared with Davis breast-fed infants, the curves for weight and length were very similar in girls until 10-12 mo and in boys until 6-9 mo. Thereafter, Huascar infants grew less rapidly than did Davis infants. Breast milk intake was very similar between groups, but in Huascar the amount and nutrient density of complementary foods consumed after 6 mo were lower and morbidity rates were much higher than in Davis. These results indicate that growth faltering of Huascar infants, when judged against breast-fed infants in the United States, occurs primarily after the first 6 mo of life and is not due to poor lactation performance. PMID- 1442652 TI - Trans-fatty acid intake in relation to serum lipid concentrations in adult men. AB - The relation of trans-fatty acid intake to fasting serum lipid concentrations was evaluated in a cross-sectional study of 748 men aged 43-85 y. Multiple-linear regression analysis was used to adjust for age, body mass index, waist-to-hip circumference ratio, smoking status, physical activity, alcohol intake, total energy, dietary cholesterol and linoleic acid, and previous serum cholesterol concentration. Trans-fatty acid intake was directly related to total serum (r = 0.07, P = 0.04) and low-density-lipoprotein cholesterol (LDL) (r = 0.09, P = 0.01), and inversely related to high-density-lipoprotein (HDL) cholesterol (r = 0.08, P = 0.03). Trans-fatty acid intake was positively associated with the ratios of total to HDL cholesterol (r = 0.11, P = 0.002) and LDL to HDL cholesterol (r = 0.12, P = 0.001). The estimated ratios of total to HDL cholesterol were 4.4 and 4.9 for persons at the 10th (2.1 g/d) and 90th (4.9 g/d) percentiles of trans-fatty acid intake, respectively. On the basis of results from other studies, these ratios would correspond to a 27% increase in risk of myocardial infarction. PMID- 1442653 TI - Nutritional effects of feeding a ketoanalogue mixture in growing and adult uremic rats. AB - Insufficient protein diets supplemented with ketoanalogue/essential amino acid (KA/EAA) mixtures are proposed to maintain nutrition and to retard renal deterioration. We compared in growing and in adult uremic rats diets containing limited or usual amounts of protein (12%, 20% for growing rats, and 10% and 16% for adult rats) with diets containing 50% or 60% less casein plus a KA/EAA mixture providing KA at an equimolar amount of removed EAA or at higher amounts. The latter supplement caused stunting, the former caused no anorexia, a slight growth deficit when added to the lowest basal casein diets, and almost normal growth when added to higher casein diets. Growth was normal with EAA supplements. The plasma EAA changes were unrelated to intake and to growth. Thus, KA utilization is maximal, provided that basal protein is sufficient and KA are not in excess. PMID- 1442654 TI - Rice: a high or low glycemic index food? AB - We determined the glycemic (GI) and insulin-index (II) values for 12 rice products, using eight healthy subjects. The products were brown and white versions of three commercial varieties of rice [two varieties with normal amylose content (20%) and the other with 28% amylose], a waxy rice (0-2% amylose), a converted rice, a quick-cooking brown rice, puffed rice cakes, rice pasta, and rice bran. The GI of the rices ranged from 64 +/- 9 to 93 +/- 11, where glucose = 100. The high amylose rice gave a lower GI and II (P < 0.01) than did the normal amylose and waxy-rice varieties. The converted rice and most other rice products gave a high GI. Insulin indices correlated positively with GI (r = 0.75, P < 0.05), although they were lower than expected. These results indicate that many varieties of rice, whether white, brown, or parboiled, should be classified as high GI foods. Only high-amylose varieties are potentially useful in low-GI diets. PMID- 1442655 TI - Calcium supplementation and plasma ferritin concentrations in premenopausal women. AB - The effect of calcium supplement use on iron stores was examined in a randomized controlled study in free-living, healthy, premenopausal women. Of 109 women who completed the study, 52 were in the control group and 57 took two tablets containing 250 mg Ca as the carbonate with each of two meals daily for 12 wk. In all subjects at baseline, plasma ferritin concentrations were positively correlated with heme-iron intake (r = 0.21, P = 0.04), serum iron concentration (r = 0.19, P = 0.04), transferrin saturation (r = 0.31, P = 0.001), and hemoglobin concentration (r = 0.22, P = 0.02), and negatively correlated with total iron-binding capacity (TIBC, r = -0.42, P < 0.001). No significant differences in absolute or percent changes in plasma ferritin concentrations, serum iron concentrations, TIBC, transferrin saturation, hemoglobin concentrations, or hematocrit were observed between the treatment and control groups. Thus, over a 12-wk period, use of 1000 mg Ca as the carbonate daily with meals does not appear to be detrimental to iron stores in healthy, free-living, premenopausal women. PMID- 1442656 TI - Iron status in exercising women: the effect of oral iron therapy vs increased consumption of muscle foods. AB - Forty-seven previously sedentary women participating in a 12-wk moderate aerobic exercise program were randomly assigned to one of four dietary groups: 50-mg/d iron supplement and a low food-iron diet (50 FE + EX), 10-mg/d iron supplement and a low food-iron diet (10 FE + EX), placebo and unrestricted diet (P + EX), and meat supplement and high food-iron diet (M + EX). A sedentary control group (n = 13) received no dietary interventions. Hematocrit, total iron-binding capacity, and hemoglobin, serum iron, serum ferritin, and serum albumin concentrations were measured every 4 wk. Hemoglobin values decreased at the end of 4 wk in all exercising groups compared with the control group. Iron status in the 50 FE + EX and M + EX groups improved after week 4 as indicated by an increase in serum ferritin, serum iron, and hemoglobin concentrations, and a decline in total iron-binding capacity. Thus, short-term, moderate aerobic exercise resulted in compromised iron status that was offset to varying degrees by ingesting iron or meat supplements. However, meat supplements were more effective in protecting hemoglobin and ferritin status than were iron supplements. PMID- 1442657 TI - Guar gum in insulin-dependent diabetes: effects on glycemic control and serum lipoproteins. AB - We examined the effect of guar gum on glycemic control and serum lipid and lipoprotein profiles in mildly hypercholesterolemic patients with insulin dependent diabetes. The study was done in a randomized, double-blind fashion with either guar gum or placebo added to the diet four times per day for 6 wk each. Fasting blood glucose and hemoglobin A1c decreased significantly during the guar gum diet, whereas the diurnal glucose profile was unchanged. In addition, serum low-density-lipoprotein (LDL) cholesterol decreased by 20% and the ratio of LDL cholesterol to high-density-lipoprotein cholesterol by 28% during guar-gum therapy. No changes were seen in the placebo group. In conclusion, guar gum can improve glycemic control and decrease serum LDL-cholesterol concentrations in mildly hypercholesterolemic insulin-dependent diabetic patients and thus reduce risk factors for both micro- and macroangiopathic complications. PMID- 1442658 TI - Guar gum improves insulin sensitivity, blood lipids, blood pressure, and fibrinolysis in healthy men. AB - A double-blind, placebo-controlled, cross-over study was carried out in 25 healthy, nonobese middle-aged men to test the effect of guar gum on glucose and lipid metabolism, blood pressure, and fibrinolysis. Ten grams guar or placebo granulate was given three times a day for 6 wk with a 2-wk run-in before and a wash-out period after. Decreases in fasting blood glucose (P < 0.001), cholesterol (P < 0.001), triglycerides (P < 0.05), plasminogen activator inhibitor-1 activity (P < 0.01), systolic blood pressure (P < 0.01), and diastolic blood pressure (P < 0.001) were seen during guar treatment when compared with placebo. Insulin sensitivity, measured with the euglycemic-clamp technique, increased (P < 0.01), adipose tissue-glucose uptake measured in vitro increased (P < 0.001), and 24-h urinary excretion of sodium and potassium increased (P < 0.001) during guar treatment. Fasting plasma insulin, renin, aldosterone, and fibrinogen concentrations as well as skeletal-muscle electrolytes, urinary catecholamines, and body weight remained unaltered. These findings support a role for guar in the treatment of the metabolic syndrome in which insulin resistance seems to play a pivotal role. PMID- 1442659 TI - New weight guidelines for Americans. PMID- 1442660 TI - Importance of electrode position in bioelectrical impedance analysis. PMID- 1442661 TI - Is 50 kHz the optimal frequency in routine estimation of body water by bio electrical impedance analysis? PMID- 1442662 TI - Protein requirements of adults from an evolutionary perspective. PMID- 1442663 TI - Body-fat measurement in patients with acquired immunodeficiency syndrome: which method should be used? AB - Malnutrition is common in patients with acquired immunodeficiency syndrome (AIDS), which distorts the chemical contents in the fat-free mass (FFM) and alters the assumptions underlying the traditional methods for calculating body fat content so that such measurements may not be accurate. In vivo neutron activation analysis (IVNA) measures FFM independently of the traditional assumptions, thereby providing more accurate measurements of body fat. We compared seven methods for measuring body fat in 18 male patients with AIDS: IVNA, total body water (TBW by 3H2O dilution), total body potassium (TBK by 40K counting), dual-photon absorptiometry (DPA), bioelectrical impedance analysis (BIA), and two well-calibrated anthropometric methods. FatTBW and fatDPA were not significantly different from fatIVNA. FatTBW gave the highest correlation with fatIVNA and the smallest SEE of +/- 1.8% (1.1 kg). The traditional and widely available TBW and the newer DPA method provide reliable estimates of fatIVNA in patients with AIDS. PMID- 1442664 TI - Resting metabolic rate and coronary-heart-disease risk factors in aerobically and resistance-trained women. AB - This cross-sectional study compared physical characteristics, cardiovascular risk factors, and resting metabolic rate (RMR) in a cohort of 82 young women separated into three groups: sedentary (SED, n = 48), aerobically trained (AT, n = 21), and resistance trained (RT, n = 13). Body mass and fat-free mass (FFM) were not different between groups whereas percent body fat was lower in the AT (16.2 +/- 0.7%) and RT (14.7 +/- 0.8%) groups than in the SED group (21.8 +/- 0.8%). There were no between-group differences for blood pressure or blood lipids. RMRs (kJ/min) for the AT (4.31 +/- 0.06) and RT (4.25 +/- 0.09) groups were significantly greater than those for the SED group (3.99 +/- 0.05). When adjusted for differences in FFM, RMRs for the AT group (4.24 +/- 0.05) were different from those of both the RT (4.13 +/- 0.05) and SED (4.05 +/- 0.03) groups; RMRs for the RT and SED groups were not different from each other. No differences were found in cardiovascular risk in young nonobese women of differing exercise status. Aerobic training in young women seems to increase the rate of metabolic activity of resting tissues whereas resistance training does not. PMID- 1442665 TI - Food selection and intake of obese women with binge-eating disorder. AB - We studied food selection and intake of 19 women [body mass index (in kg/m2) > 30] [corrected], 10 of whom met proposed DSM-IV criteria for binge-eating disorder (BED). All subjects ate two multicourse meals in the laboratory, and were given tape-recorded instructions at each meal either to binge or eat in a normal fashion. Subjects with BED consumed significantly more energy than did subjects without BED at both the binge [12,400 vs 8440 kJ (2963 vs 2017 kcal), P < 0.005] and normal [9810 vs 6870 kJ (2343 vs 1640 kcal), P < 0.02] meals. During the binge meal subjects with BED consumed a greater percentage of energy as fat (38.9% vs 33.5%, P < 0.002) and a lesser percentage as protein (11.4% vs 15.4%, P < 0.01) than did subjects without BED. There were no differences in macronutrient composition of food choices between groups in the normal meal. Obese women who meet criteria for BED show differences in both intake and macronutrient composition of food choices from obese women who do not meet these criteria when asked to eat in a laboratory setting, supporting the validity of this new diagnosis. PMID- 1442666 TI - Resting metabolic rate, body-fat distribution, and visceral fat in obese women. AB - Resting metabolic rate (RMR) was evaluated in 27 obese women aged 16-49 y [body mass index (in kg/m2) 27-51] by indirect calorimetry. Visceral and subcutaneous adipose tissue areas, body fat, and fat-free mass (FFM) were measured by a single scan with computed tomography (CT); the waist-hip circumference ratio (W/H) was also used. Comparison between the lowest and the highest RMR quartiles--adjusted for age and FFM--revealed a higher W/H in the highest quartile (0.78 +/- 0.08 vs 0.88 +/- 0.08; P < 0.05). No difference was observed in CT indexes. No differences in W/H were observed after RMR was adjusted for age, FFM, and body fat. Our results point out that RMR, adjusted for FFM and age, correlates with body-fat distribution as evaluated by W/H, but not with visceral fat, as evaluated by CT. Correlations disappeared after RMR was adjusted for body fat as well. PMID- 1442667 TI - Cross-sectional study on the iron and vitamin A status of pregnant women in West Java, Indonesia. AB - A cross-sectional study of the prevalence of iron and vitamin A deficiency in normal pregnant women in West Java, Indonesia, was carried out. Of the 318 women studied, 49.4% were anemic and, according to multiple criteria, 43.5% had iron deficiency anemia, 22.3% had iron-deficient erythropoiesis, and 6.6% had iron depletion. Serum retinol values revealed that 2.5% of the pregnant women were vitamin A deficient and 31% had marginal vitamin A status. The relative dose response test carried out on 45 women showed that 4 (8.9%) had deficient vitamin A liver stores. After gestational stage, parity, and subdistrict were adjusted for, serum retinol concentrations were significantly positively associated (P < 0.01) with hemoglobin concentrations, hematocrit, and serum iron concentrations. The suboptimal vitamin A status associated with nutritional-deficiency anemia suggests that pregnant women in the area should be supplemented not only with iron but also with vitamin A. This proposal should be tested in an intervention study. PMID- 1442668 TI - Evaluation of the impact of weaning food messages on infant feeding practices and child growth in rural Bangladesh. AB - In rural Bangladesh, a community-based weaning intervention used volunteers to teach complementary feeding to families of 62 breast-fed infants aged 6-12 mo. Over 5 mo, treatment children gained on average 0.46 SD (approximately 460 g) more in weight-for-age (WAZ) than the 55 control subjects, and were approximately 0.5 kg heavier at the final measure. The differences were statistically significant (P < 0.001). The percent median weight-for-age (WAPM) of treatment children held steady at 76% of the National Center for Health Statistics' reference, whereas the WAPM of control subjects dropped from 78% to 72%. The increase in percentage points of severe malnutrition (below -3 WAZ) was only 5% in the treatment group compared with 26% in the control subjects. Treatment children consumed a significantly greater percent of their energy and protein requirements from complementary foods than did control subjects. The affordable complementary foods consisted mainly of cereal porridge with oil and brown sugar. These findings suggest that educational interventions teaching families to feed hygienic, simple, cheap, energy-enriched complementary foods to breast-fed infants after 5-6 mo can improve child growth, even under impoverished conditions. PMID- 1442669 TI - H. pylori causes cancer: true or false? PMID- 1442670 TI - Preventing ERCP-induced pancreatitis. PMID- 1442671 TI - Up close and personal: a president's perspective. PMID- 1442672 TI - Advances in enteral nutrition techniques. AB - The increasing use of enteral nutrition in hospitals has led to an expanded role for the gastroenterologist and surgeon in providing enteral access. New concepts in immunonutrition and gut support in critically ill patients have popularized early postoperative feeding. There is an ongoing need to update physicians on the diverse enteral access techniques now available. In addition to standard percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic jejunostomy (PEJ) techniques, this review focuses on reflux prevention through double-lumen feeding-suction tubes, and describes the use of steerable catheters for rapid insertion of nasojejunal and PEJ tubes without endoscopy. Low-profile "button" type devices, one-step button placement, replacement gastrostomy devices, and special enteral techniques for patients with cancer are also reviewed. PMID- 1442673 TI - High prevalence and persistence of cytotoxin-positive Helicobacter pylori strains in a population with high prevalence of atrophic gastritis. AB - Helicobacter pylori is strongly associated with both chronic gastritis and duodenal ulcer. Certain strains of H. pylori produce a vacuolating cytotoxin in vitro. At New Orleans Charity Hospital, concentrated culture supernatants from 119 of 144 (83%) H. pylori strains isolated from 86 patients at high risk of developing gastric cancer, caused vacuolization in HeLa S3 cells. Cytotoxin activity was neutralized by acid (pH 4) and basic (pH 10) solutions and proteases, and was precipitable by (NH4)2SO4, which suggests that the cytotoxin is a protein. In 66 of 86 (76.7%) patients, the H. pylori strains isolated from single or multiple sequential gastric biopsies had a vacuolating cytotoxin. These cytotoxin-positive H. pylori strains were isolated from 69% of patients with diffuse antral gastritis and 89% of patients with chronic atrophic gastritis. The latter lesion is considered a precursor of gastric cancer. The cytotoxicity persisted in sequential biopsies over an interval of several months, indicating persistence of these strains in the gastric mucosa. Fifty-eight percent (7/12) of the sera from cytotoxin-positive H. pylori-infected patients neutralized cytotoxin activity, whereas 20% (1/5) of sera from patients with H. pylori cytotoxin-negative strains and none of five H. pylori-negative patients' sera neutralized cytotoxin activity. The relevance of this cytotoxin in the pathogenesis of H. pylori-induced gastritis requires further study. PMID- 1442674 TI - Manometric and radiologic correlations in achalasia. AB - Achalasia is an esophageal motor disorder distinguished by clinical, radiologic, and manometric features. To evaluate the correlation among these features, we studied 109 achalasia patients. The four most common clinical complaints, the four most commonly encountered radiologic findings, and two manometric parameters were analyzed with a correlation matrix test and a multiple regression analysis. Significant correlation existed among symptoms of dysphagia, regurgitation, and weight loss. In contrast, chest pain inversely correlated with these symptoms. Dysphagia and weight loss significantly correlated with a bird-beak deformity but not with esophageal dilatation or a sigmoid esophagus. Moreover, no significant relationship between lower esophageal sphincter pressure and esophageal dilatation or sphincter pressure and sigmoid esophagus was found. However, in those patients with a resting lower esophageal sphincter pressure greater than 45 mm Hg, a reasonable correlation among clinical, radiologic, and manometric parameters did exist. In conclusion, although in a subset of patients with markedly increased lower esophageal sphincter pressure, a good correlation between clinical, radiologic, and manometric findings exists, such a correlation cannot be established in all of the achalasia patients; esophageal dilatation or a sigmoid esophagus may not be due to a hypertensive sphincter, and their presence must not necessarily be interpreted as an indication of severity of the disease; there is an inverse correlation between chest pain and symptoms of dysphagia, regurgitation, and weight loss; and finally, achalasia and hiatal hernia may coexist in 6% of the patients. PMID- 1442675 TI - Yield of upper endoscopy in the evaluation of asymptomatic patients with Hemoccult-positive stool after a negative colonoscopy. AB - The yield of upper endoscopy in asymptomatic patients with positive fecal occult blood test (FOBT) and a negative colonoscopy was evaluated prospectively in 70 consecutive patients. Significant pathology was diagnosed in 19 patients (27%), eight patients with ulcers, five with arteriovenous malformations, three with esophageal or gastric varices, two with multiple erosions, and two with biopsy proven Barrett's esophagus. Thirteen patients had iron deficiency anemia and demonstrated a 38% prevalence of significant pathology. Fifteen patients on nonsteroidal anti-inflammatory agents had a 30% prevalence of significant pathology. No statistically significant difference was noted between subgroups. In conclusion, asymptomatic patients without a colonic source to explain a positive FOBT often have significant lesions, on upper endoscopy. Iron deficiency anemia did not have an impact on pathology. Because treatment and follow-up plans were altered in many of the cases in which significant pathology was demonstrated, we conclude that upper endoscopy should be seriously considered for all asymptomatic patients with occult gastrointestinal bleeding and a negative colonoscopic examination. PMID- 1442676 TI - Comparison of fecal occult blood tests for detection of gastrointestinal bleeding in pediatric patients. AB - To compare fecal occult blood tests (Hemoccult II, Hemoccult SENSA, HemeSelect) for detecting the presence of occult gastrointestinal bleeding in a pediatric population at high risk, we analyzed stool specimens from 100 children who followed a restricted diet. Forty-two children had upper and 58 lower gastrointestinal sources of bleeding. Positivity rates ranged from 10.8% to 26% dependent upon the occult blood test. Whereas Hemoccult II and Hemoccult SENSA slides detected several positive specimens in upper gastrointestinal bleeding sources, all HemeSelect slides were negative in these subjects. In lower gastrointestinal bleeding, HemeSelect slides were positive in 26.8% of samples as opposed to 15.9% and 17.5% positivity rates for Hemoccult II and Hemoccult SENSA, but this difference was not statistically significant. We conclude that fecal occult blood tests vary, depending upon the origin of bleeding. Our results favor use of Hemoccult SENSA slides for suspected upper gastrointestinal bleeding and HemeSelect slides for lower gastrointestinal bleeding in children. However, if only one all-purpose fecal occult blood test is to be utilized, then our data supports the use of Hemoccult SENSA slides for children. PMID- 1442677 TI - Effect of triglycyl-lysin-vasopressin on quantitative liver function tests in patients with cirrhosis. AB - The effects of vasopressin and of its analogues on liver function, and their possible mechanisms of action, are poorly understood. This study was designed to assess the effect of triglycyl-lysin-vasopressin on liver function, evaluated by two quantitative tests independent of liver blood flow, i.e., indocyanine green intrinsic hepatic clearance and galactose elimination capacity. Indocyanine green intrinsic hepatic clearance and galactose elimination capacity were determined before and after administration of 2 mg triglycyl-lysin-vasopressin to (respectively) 10 and 12 patients with cirrhosis. Eighteen additional patients with cirrhosis were studied before and after infusion of placebo. No significant variation in either test was observed in placebo-treated patients. A significant decrease in indocyanine green intrinsic hepatic clearance, averaging 22%, was observed in patients receiving the drug (p = 0.04). Conversely, galactose elimination capacity remained unchanged after the drug. These results are compatible with the hypothesis that the drug produced a preferential decrease in perfusion in functioning areas of the liver, with relative maintenance of blood flow in non-functioning areas. PMID- 1442678 TI - Seasonal fluctuations in acute upper gastrointestinal bleeding: lack of effect of nonsteroidal anti-inflammatory drugs. AB - The seasonal pattern of community-based acute bleeding from the upper gastrointestinal (UGI) tract was studied prospectively in 1988-1991. Out of 3343 emergency admissions to the Departments of General Surgery, 321 (9.6%) were due to acute UGI bleeding. There was a significant monthly variation in the total number of admissions, as well as in the number of admissions due to acute UGI bleeding (p < 0.0001). However, there was no correlation between the two. Significant seasonal fluctuations were noted both in the absolute number of admissions due to acute UGI bleeding and in the percentage of UGI bleeding admissions of the total number of admissions to the Departments of General Surgery (p = 0.0002). During summer (July through September), the incidence declined significantly to a nadir of 5.5% of total number of admissions in July. The seasonal fluctuation correlated closely with the incidence of duodenal ulcer, but not with that of gastric ulcer. The seasonal pattern was consistent both in patients who had used aspirin or other nonsteroidal anti-inflammatory drugs as well as in those who had not. PMID- 1442679 TI - Is duodenal ulcer a seasonal disease? A retrospective endoscopic study of 3105 patients. AB - The monthly pattern of distribution of endoscopically diagnosed duodenal ulcer disease was evaluated for the years 1975-1989. A retrospective review of 3105 endoscopies performed for peptic disease was recorded and analyzed. Among them, 2020 endoscopies revealed duodenal bulb deformity, and 1035 revealed the presence of acute duodenal ulcer. Chi-square analysis of the data for goodness of fit revealed statistical differences for certain months. Slightly more patients with chronic deformity presented in June and November, whereas more patients with acute duodenal ulcer presented in July, November, and December (p < 0.001). The ratio of acute to chronic disease was nearly constant throughout the year. The Edwards chi 2 test for seasonal trends did not reveal any seasonality (p > 0.75). The differences observed in June-July and November-December, as compared with the rest of the year, were so small that they should not be relied upon for the clinical management of peptic disease. PMID- 1442680 TI - Prospective evaluation of Foley catheter as a replacement gastrostomy tube. AB - Percutaneous endoscopic gastrostomy provides a nonsurgical alternative to enteral feeding. However, the percutaneous endoscopic gastrostomy tube may deteriorate, malfunction, or be accidentally expelled from the stomach, requiring replacement. This prospective study was performed to evaluate the use of an all silicone Foley catheter (Foley) as a replacement feeding gastrostomy in 28 patients requiring replacement gastrostomy. A plastic ring and a retention disc were always placed over the Foley prior to replacement. Foley functioned well without replacement in 19 (68%) patients for a mean of 167 days. It needed to be replaced in nine (32%) patients due to malfunction after a mean of 138 days. Lack of migration of Foley was the most striking finding of our study, in contrast to case reports in the literature. These data suggest that Foley can be safely used as replacement gastrostomy tube. A randomized controlled trial comparing the Foley catheter as a replacement tube with other commercially available devices is needed. PMID- 1442681 TI - Prevalence and significance of Helicobacter pylori in patients with Barrett's esophagus. AB - A retrospective study for assessment of the prevalence of Helicobacter pylori was performed in 107 consecutive patients with columnar-lined epithelium in the esophagus. The presence of hiatal hernia and esophagitis was noted. From 71 patients, biopsy specimens were available for analysis. No difference in the presence or absence of H. pylori was noted, regardless of whether or not there was esophagitis or hiatal hernia. Most H. pylori-positive patients show a low bacterial load in the metaplastic epithelium. It is assumed that the finding of H. pylori in columnar-lined epithelium reflects a shift in the bacterium from the gastric antrum. H. pylori probably has no etiologic role of esophagitis in Barrett's mucosa. PMID- 1442682 TI - Optimal nonsurgical treatment of hemorrhoids: a comparative analysis of infrared coagulation, rubber band ligation, and injection sclerotherapy. AB - Despite an abundance of nonsurgical hemorrhoid therapies, none has been consistently more efficacious. By combining data from multiple clinical trials in a meta-analysis, the present study compared the efficacy and complications of infrared coagulation, injection sclerotherapy, and rubber band ligation to determine the optimal nonoperative hemorrhoid treatment. All published clinical trials comparing the three methods were identified by computer search and review of appropriate English language journals. Five trials studying 863 patients satisfied all inclusion criteria. Results demonstrated that similar numbers of patients were asymptomatic 12 months after treatment, regardless of initial therapy. However, significantly fewer patients undergoing rubber band ligation required additional treatment because symptoms had recurred. Although rubber band ligation demonstrated greater long-term efficacy, it was associated with a significantly higher incidence of posttreatment pain. In contrast, infrared coagulation was associated with both fewer and less severe complications. Thus, when all factors are considered, infrared coagulation may in fact be the optimal nonoperative hemorrhoid treatment. PMID- 1442683 TI - Fistulosphincterotomy in the endoscopic approach to biliary tract diseases. AB - We report our experience with 49 patients who underwent fistulosphincterotomy (FS) after cannulation of the common bile duct (CBD) by standard approaches had failed, due to suspected CBD obstruction. Only 4% of our cases turned out to have no biliary obstruction at all. The morbidity rate was 16%, and the mortality rate was 2%. In our series, FS raised the success rate of CBD cannulation from 90% to 96%. Ninety-five percent of successful cannulations were followed by endoscopic treatment. There were no cases of perforation or hemorrhage, and no difference in the success rate between FS in flat papillas and FS in bulging papillas, thanks, perhaps, to the technique we used. Our findings would indicate that FS is a useful procedure involving additional but not prohibitive risks. Nonetheless, it should be used only when CBD obstruction is strongly suspected and standard methods are not successful. PMID- 1442684 TI - CT-guided needle biopsy of the pancreas: a retrospective analysis of diagnostic accuracy. AB - The purpose of this study was to evaluate the accuracy of percutaneous needle biopsy of the pancreas and to compare its sensitivity with that of simple computerized tomographic (CT) prediction of malignancy. The records of 41 patients who underwent CT-guided percutaneous needle biopsies of the pancreas during a 4-yr period were reviewed retrospectively. Pre-biopsy CT scans were evaluated independently by two experienced radiologists in a blinded fashion. Needle biopsy yielded a correct diagnosis of cancer (sensitivity) in only 45% of patients ultimately found to have a malignancy, whereas the radiologic interpretation alone correctly predicted cancer in 76% of such patients. The negative predictive value of needle biopsy was no better (43%) than the radiologist's CT interpretation alone. Our findings confirm previous observations that percutaneous needle biopsy is an insensitive method of diagnosing pancreatic cancer. In our experience, needle biopsy proved less accurate than expert radiologic interpretation of CT scans alone. PMID- 1442685 TI - Gastrointestinal transit after spinal cord injury: effect of cisapride. AB - Heartburn, bloating, and abdominal discomfort are common problems in patients with spinal cord injury but, despite its clinical significance, little is known about the gastrointestinal effects of spinal transections. To address the potential gastrointestinal pathophysiology of spinal cord injury, we measured mouth-to-cecum transit time (MCTT) in seven subjects with paraplegia and seven with quadriplegia. Gastric emptying was studied in six subjects with quadriplegia. MCTT was significantly prolonged in patients with quadriplegia, an abnormality corrected by the administration of cisapride. Patients with paraplegia, in contrast to those with quadriplegia, have normal mouth-to-cecum transit time. In addition, patients with quadriplegia had neither a prolonged gastric emptying time nor a change in gastric emptying time, with cisapride. Changes in gastrointestinal transit after spinal cord injury and the improvement of mouth-to-cecum transit time in subjects with quadriplegia, but not in those with paraplegia, may be explained by an imbalance between parasympathetic and sympathetic outflows to the gastrointestinal tract in this group of subjects. PMID- 1442686 TI - Endoscopic ultrasonography findings in acute gastric anisakiasis. AB - To clarify the components of the thickened gastric wall in acute gastric anisakiasis, we evaluated endoscopic ultrasonography (EUS) findings of acute gastric anisakiasis. Ten patients with acute gastric anisakiasis underwent endoscopic ultrasonography immediately after anisakiasis was diagnosed by endoscopy. In the acute phase of gastric anisakiasis, endoscopic ultrasonography (EUS) detected a thickening of the gastric wall made of mainly thickened third layer with low echoic changes. When EUS was performed 7 to 11 days later in seven patients, the EUS findings had normalized. We made clear EUS findings in acute gastritis due to gastric anisakiasis. Consequently, we found, by EUS, that the main inflammatory lesion in anisakiasis was in the submucosal layer of gastric wall. PMID- 1442687 TI - Detection of HIV-1 protein and nucleic acid in enterochromaffin cells of HIV-1 seropositive patients. AB - Diarrhea contributes significantly to the morbidity and mortality of patients with the acquired immunodeficiency syndrome (AIDS). Up to 50% of AIDS patients have diarrhea, and an etiologic agent for this cannot be identified in all of them. Recent evidence suggests that enterochromaffin cells may be infected by the human immunodeficiency virus type 1 (HIV-1) and may contribute to the unexplained diarrhea. To test this hypothesis further, endoscopic biopsies of duodena from 22 HIV-1 seropositive patients [17 with diarrhea (> 500 g/day and > 3 bowel movements/day), five without diarrhea] and from 15 normal controls (no HIV risk factors) without diarrhea were studied. Formalin-fixed and paraffin-embedded 5 microns sections were examined by immunocytochemistry, using a monoclonal antibody to the HIV-1 gp41 protein, and by in situ hybridization with a full length biotinylated HIV-1 DNA probe. Positive staining for gp41 was detected in crypt cells, consistent with the location, size, and morphology of enterochromaffin cells, in 11 of 17 HIV-1-seropositive patients with diarrhea, and in none of five without diarrhea. Nucleic acid hybridization staining was performed in five of the 11 patients who had positive gp41 staining; all showed HIV nucleic acid sequences in similar cells. All three of the five patients with positive staining for HIV nucleic acid sequences had diarrhea for which no etiologic agent for diarrhea could be found, and one each had cryptosporidia or microsporidia. No staining was observed in any of the samples from normal control tissues. These results suggest that HIV-1 may infect enterochromaffin cells and possibly alter their function. This, in turn, may contribute to the diarrhea associated with AIDS. PMID- 1442688 TI - Dysgonic fermenter-3: a bacterium associated with diarrhea in immunocompromised hosts. AB - We describe two patients with chronic diarrhea associated with dysgonic fermenter 3 (DF-3) infection. One patient had common variable hypogammaglobulinemia and the other hand chronic idiopathic neutropenia and human immunodeficiency virus infection. Specific stool culture techniques were necessary to isolate DF-3. The organism was sensitive to clindamycin, tetracycline, and trimethoprim sulfamethoxazole. Antibiotic therapy eradicated the organism and the diarrhea resolved in both patients. DF-3 is a little-recognized organism associated with diarrhea in the immunocompromised patient. It should be suspected when routine evaluation and stool cultures are not diagnostic. PMID- 1442689 TI - Pseudomembranous enteritis: rediscovery of a previously well-described entity? PMID- 1442690 TI - Association of gluten-sensitive enteropathy and Crohn's colitis. PMID- 1442691 TI - Crohn's disease associated with cyclic neutropenia. AB - Crohn's disease and neutropenia unrelated to drug therapy is a rare association. We present a case of Crohn's disease associated with cyclic neutropenia. Our patient, observed over 10 yr, is unique due to the lack of recurrent bacterial infections or other associated sequelae of the neutropenic state. There was no consistent association between white blood cell cycling and exacerbations of her Crohn's disease. However, the latter did appear to worsen the neutropenic state. A clear pattern of cyclic neutropenia became apparent only when the disease was quiescent and all medications had been discontinued. We report this case for its value in pursuing clinically and therapeutically appropriate options, including surgery and drugs with neutropenic potential, in patients with Crohn's disease and, possibly, white blood cell abnormalities. PMID- 1442692 TI - Fulminant hepatitis B and delta virus coinfection in AIDS. PMID- 1442693 TI - Acute pancreatitis associated with acute hepatitis A. AB - The etiology of acute pancreatitis is diverse, and unusual causes include several common viral infections. Although pancreatitis has been found at autopsy in patients with fulminant hepatic failure, there have been only a few reports of an association between mild to moderate acute viral hepatitis and acute pancreatitis. A case of acute hepatitis A complicated by acute pancreatitis is presented, and the relevant literature regarding this unusual association is reviewed. PMID- 1442694 TI - Spontaneous splenic rupture complicating acute Q fever. AB - Q fever is usually a self-limited febrile illness that involves the lungs and the liver. Acute complications are rare. We present the case of a 30-yr-old patient with spontaneous splenic rupture during the course of acute Q fever infection. He was admitted to the hospital with high temperature and the radiological signs of an atypical pneumonia. Forty-eight hours after admission, he developed shock. Because of free intraabdominal liquid, a laparatomy was performed that revealed a tear in the enlarged spleen. A splenectomy was performed. The diagnosis of Q fever was established by a significant titer increase in complement fixation test and IgM-ELISA. Serological investigations into the patient's surroundings revealed evidence of Q fever infection in 10 additional persons. Q fever should be taken into account as a possible differential diagnosis in patients with unexplained febrile illness and symptoms of pneumonia. The acute course of Q fever infection can be complicated by splenic rupture. The diagnosis of an acute infection with Coxiella burnetii often requires serologic testing of a second serum sample obtained at least 10 days after the onset of symptoms. Q fever should be ruled out in cases of unexplained splenic rupture particularly in Q fever endemic areas. PMID- 1442695 TI - The treatment of isolated pancreatic metastases from renal cell carcinoma: a surgical review. AB - The pancreas is an uncommon site of metastasis for renal cell carcinoma. Multiple metastasis to the pancreas from a renal cell carcinoma 17 yr after the primary diagnosis is even more uncommon. Such a case, treated by total pancreatectomy, and a review of the relevant literature including all recorded cases of surgically treated pancreatic metastasis of renal cell carcinoma, are presented. PMID- 1442696 TI - Sickle cell crisis and cocaine hepatotoxicity. AB - Hepatic dysfunction occurs in up to 10% of patients with sickle cell crisis; however, hepatic failure is quite unusual. Cocaine hepatotoxicity has recently been recognized in humans with liver biopsies showing varying patterns of necrosis. Most patients reported with cocaine intoxication have rhabdomyolysis with renal failure, and half of the cases have been fatal. A patient with concomitant sickle cell crisis and cocaine intoxication presented with hepatic failure, coagulopathy, and encephalopathy. Transjugular liver biopsy showed focal areas of confluent necrosis and large areas of collapse. Cocaine intoxication should be considered in the differential diagnosis of hepatic failure in patients with sickle cell anemia. PMID- 1442697 TI - Cervical soft tissue metastasis of typical carcinoid tumor preceding diagnosis of ileal primary by 4 years. AB - A solitary cervical metastasis of a typical carcinoid tumor was found in the subcutaneous tissue of an asymptomatic 38-yr-old woman. Investigations failed to disclose the primary site until the 5th yr, when she presented with carcinoid syndrome. Multifocal ileal carcinoid tumors were resected and debulking of abdominal metastases performed. Interferon and somatostatin analogue treatment resulted in remission. Solitary cervical metastasis is an exceedingly rare initial manifestation of a mid-gut carcinoid tumor, and poses a therapeutic dilemma. There are no directions in the literature as to whether a "wait-and-see" approach or exploration surgery is the preferred management when one is confronted by a cervical metastasis of typical carcinoid tumor of unknown primary site. PMID- 1442698 TI - Acute esophageal obstruction: a unique presentation of a giant intramural esophageal leiomyoma. AB - We report the case of a 33-yr-old man who presented with an acute incomplete esophageal obstruction, mimicking food impaction, who was found to have a giant intramural esophageal leiomyoma. The leiomyoma was successfully removed through a longitudinal esophagotomy. This is the first report of a nonpedunculated intramural esophageal leiomyoma presenting as an acute esophageal obstruction. PMID- 1442699 TI - Ascites: to drain or recirculate. PMID- 1442700 TI - Old habits may be hard to break. PMID- 1442701 TI - Colonic motility in ulcerative colitis: muscling in on a mucosal disease? PMID- 1442702 TI - Reflux-associated esophageal spasm. PMID- 1442703 TI - Pepto-Bismol mimicking pancreatic calcification. PMID- 1442704 TI - Guidewire loop formation in common bile duct during biliary manometry. PMID- 1442705 TI - Combined injection and thermal therapy in the management of early post polypectomy bleeding. PMID- 1442706 TI - Natural history of erosive duodenitis. PMID- 1442707 TI - Volvulus of the sigmoid colon associated with eventration of the diaphragm. PMID- 1442708 TI - Gastrostomy tube deterioration and fungal colonization. PMID- 1442709 TI - Percutaneous endoscopic gastrostomy. PMID- 1442710 TI - Chronic urticaria atopic dermatitis and celiac disease. PMID- 1442711 TI - Olsalazine sodium can cause myopia that can be clinically confused with the uveitis of inflammatory bowel disease. PMID- 1442712 TI - Transrectal ultrasonographic demonstration of rectal varices. PMID- 1442713 TI - Gallbladder perforation presenting as significant hyperbilirubinemia. PMID- 1442714 TI - Autoimmunity and genetics contribute to the risk of insulin-dependent diabetes mellitus in families: islet cell antibodies and HLA DQ heterodimers. AB - The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies may be relatively common, it progresses only in those with variant HLA-DQ molecules. PMID- 1442715 TI - The relation of prothrombin times to coronary heart disease risk factors among men aged 31-45 years. AB - Although levels of coagulation factor VII and fibrinogen are predictive of cardiovascular disease, relatively little data describe hemostatic characteristics in healthy populations. The cross-sectional associations between the prothrombin time, a measure of the activity of the extrinsic and common pathways of coagulation, and traits associated with the risk of cardiovascular disease were therefore examined among 3,604 white and 514 black, male, US Army veterans aged 31-45 years. The prothrombin time measurements, performed in 1985 and 1986, were precise, with an intraclass correlation of 0.98 (202 pairs). Overall, the mean prothrombin time was 12.4 seconds (standard deviation, 0.4 seconds), and 11 percent of the men had a value of less than 12 seconds. Many of the observed associations with the prothrombin time paralleled those that have been reported with clotting factor VII and fibrinogen. The mean prothrombin time was 0.15 seconds shorter among whites than among blacks and was 0.2 seconds shorter among current cigarette smokers than among men who had never smoked. Inverse associations were also seen with relative weight and with levels of total cholesterol and triglycerides (r = -0.09 to -0.16). All associations were statistically significant at the 0.01 level, and the examined characteristics could jointly account for about 12 percent of the variability in prothrombin times. Additional data on characteristics related to coagulation may help elucidate the natural history of cardiovascular disease and aid in the design of clinical trials. PMID- 1442716 TI - Leukocyte count correlates in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. AB - Cross-sectional associations between leukocyte count and sociodemographic and cardiovascular risk factors were investigated in 14,679 participants aged 45-64 years in the Atherosclerosis Risk in Communities Study carried out in four US communities in 1986-1989. Leukocyte count was strongly associated with present or past history of cigarette smoking and was higher in males than in females and in white subjects than in black subjects. Among never smokers, no sex differences were evident after adjustment for other risk factors. Race-associated differences were substantially reduced after other factors were taken into account in multivariate analyses. In never smokers, leukocyte count was higher in those who reported poor health, and it was inversely associated with high density lipoprotein cholesterol, forced expiratory volume at 1 second, physical activity, and, among whites, height and socioeconomic indicators. It was directly associated with indices of body weight and body fat, heart rate, blood pressure, hemoglobin, platelet count, uric acid, fasting insulin and glycemia, triglycerides, fibrinogen, antithrombin III, protein C, factors VII and VIII, and von Willebrand factor. The associations of leukocyte count with cardiovascular risk factors may either represent manifestation of subclinical disease or suggest that leukocyte count is part of the causal chain leading to atherosclerosis. Alternatively, the relation of leukocyte count to cardiovascular disease may be confounded by risk factors and thus be noncausal. PMID- 1442717 TI - Postprandial lipemia: reliability in an epidemiologic field study. AB - Ten subjects from the Forsyth County, North Carolina, and Washington County, Maryland, field centers in the Atherosclerosis Risk in Communities Study had two fat tolerance tests within a 10-day period from September 1988 to February 1989 to determine the reproducibility of markers for postprandial lipemia. No significant differences between visits were found in fasting mean plasma lipids, lipoproteins, and apolipoproteins. Postprandial triglycerides and retinyl palmitate were measured at 3.5 and 9.0 hours after the test meal in whole plasma. There were no significant differences in the mean levels of these analytes between visits. The correlation of triglycerides between repeat visits at 9.0 hours (r = 0.87) was stronger than in fasting samples (r = 0.67) or at 3.5 hours (r = 0.69). The mean plasma retinyl palmitate level at 3.5 hours was 15% higher than at the 9.0-hour level. The correlation of repeat measures of retinyl palmitate at 9.0 hours (r = 0.94) was much stronger than at 3.5 hours (r = 0.79). In conclusion, estimates of reliability in postprandial measurements of 9.0-hour triglycerides and retinyl palmitate levels were as strong as fasting lipid measurements of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol, and both postprandial triglyceride measurements exceeded that of fasting triglyceride (r = 0.67). PMID- 1442718 TI - The relation of high density lipoprotein cholesterol and its subfractions to apolipoprotein A-I and fasting triglycerides: the role of environmental factors. The Atherosclerosis Risk in Communities (ARIC) Study. AB - Cross-sectional analysis of four general representative populations of middle aged adults in the United States in 1986-1989 provides estimates of the close relation of high density lipoprotein cholesterol (HDL cholesterol) to its major structural apolipoprotein (apolipoprotein A-I) and to fasting plasma triglyceride levels. HDL cholesterol differences of approximately 0.4 mg were associated with 1-mg differences in apolipoprotein A-I; differences of 20% in HDL cholesterol (reductions) were associated with triglyceride doublings. Variation in apolipoprotein A-I and triglyceride concentration together accounted for 66% of the population variance in HDL cholesterol. The uniformity of this pattern in the four race-sex groups studied suggests an important role of triglyceride cholesterol transfer as a determinant of HDL cholesterol. The fundamental relations observed among HDL cholesterol, apolipoprotein A-I, and triglycerides were unaltered by levels of factors under personal volition. The volitional factors appeared to influence HDL cholesterol indirectly: Obesity and physical activity were affected primarily through their associations with triglycerides, and alcohol use and smoking through associations with apolipoprotein A-I. The association of alcohol use with elevated HDL cholesterol was attenuated in persons with greater body mass. PMID- 1442719 TI - Is stroke mortality on the decline in England? AB - This paper challenges the assumption that mortality from stroke will remain constant or decline over the next few decades. A decline in stroke mortality could be brought about by changes in factors acting close to the time of death (period effect) or by risk factors determined by the generation into which a person is born (cohort effect). Age-specific death rates for stroke (1931-1985) in England and Wales were analyzed to estimate the influence of these different effects. There were significant effects for age, period, and cohort on mortality from stroke with significantly different age and period effects in each sex. The effect of age was linear, with an increasing mortality with age in both sexes. Cohort analysis demonstrated a deceleration away from the previous trend in the mortality rates associated with birth cohorts born after 1880, followed by an acceleration in the trend of mortality rates in cohorts born after 1910. These relative increases in risk for cohorts born after 1910 were offset by a deceleration in mortality associated with periods from around 1951-1954. Since cohort effects are likely to be associated with a lifetime increase in risk of stroke mortality, it is difficult to predict the extent of any long-term fall in stroke incidence. PMID- 1442720 TI - Agreement between maternal interview- and medical record-based gestational age. AB - Agreement between maternal interview- and medical record-based gestational age was assessed by using data from a case-control study of childhood strabismus. The sample consisted of 383 cases of strabismus and their age-matched controls, diagnosed between 1985 and 1986 in Baltimore, Maryland, who were under age 7 years when diagnosed. Medical record-based gestational age was derived, in order of priority, from early ultrasound examination, time from the last menstrual period, pediatric examination, and obstetric examination. The intraclass correlation coefficient, kappa, and mean difference were used to compare agreement between maternal interview- and medical record-based gestational age by maternal and pregnancy characteristics and characteristics related to study design. Overall, 86 percent of mothers were within 2 weeks of the gestational age reported in the medical record. The intraclass correlation coefficient comparing maternal and medical record-based gestational age was 0.83 (95% confidence interval 0.80-0.86). Agreement was positively associated with shorter length of recall, low birth order, and having a neonatal illness related to prematurity. Agreement was poor among mothers of healthy preterm infants. There was a weak positive association between recall and some sociodemographic covariates. There was greater misclassification of prematurity in the controls than in the cases. The results suggest that, in general, women recall gestational age well, which supports the use of gestational age derived from maternal interviews. PMID- 1442721 TI - Maternal nutrition and spontaneous preterm birth. AB - Previous studies suggesting that maternal undernutrition increases the risk of preterm birth have suffered from several methodological shortcomings, including use of total gestational weight gain rather than net rate of gain in maternal tissue, inclusion of induced preterm deliveries, and error-prone gestational age measurements based solely on menstrual dates. The authors have attempted to overcome these shortcomings by investigating the potential etiologic roles of prepregnancy body mass index, net rate of maternal weight gain, height, and a number of other potential biological and sociodemographic determinants of spontaneous (i.e., noninduced) preterm birth in a cohort of 13,102 women with early ultrasound-confirmed gestational age who delivered at the Royal Victoria Hospital in Montreal, Quebec, Canada, between January 1, 1980 and March 31, 1989. Total weight gain, but not body mass index, was highly significantly associated with spontaneous preterm birth, averaging 14.6, 12.5, 9.9, and 9.1 kg, in women delivering at 37 or more, less than 37, less than 34, and less than 32 completed weeks, respectively. Although the relation persisted when weight gain was expressed as an overall rate, it disappeared when the analysis was based on net rate; mean net rates of gain were 0.28, 0.29, 0.27, and 0.27 kg/week, respectively. On the basis of multiple logistic regression analyses, significant determinants of birth at less than 37 weeks included maternal short stature; noncompletion of high school; unmarried status; smoking; diabetes; urinary tract infection within 2 weeks of delivery; prepregnancy hypertension; severe pregnancy induced hypertension; and previous history of preterm delivery, low birth weight, or neonatal death. Most of these factors retained their significance for birth at less than 34 and less than 32 weeks. In fact, the effect of low maternal education was even stronger at these more severe "levels" of preterm birth. The authors conclude that prepregnancy weight-for-height and gestational weight gain are not important determinants of spontaneous preterm birth and that some previous studies have mistaken an effect of shortened gestation for its cause. Other biologic and social determinants, however, indicate priorities for future research and intervention. PMID- 1442722 TI - The geographic structure of measles epidemics in the northeastern United States. AB - The incidence of disease across geographic space often produces distinctive regional patterns. In this paper, a modeling approach to the identification of the factors that shape the patterns is presented, and a procedure for fitting the model to observed data is given. The methodology is illustrated by an application to the geographic structure of measles epidemics among 22 states of the northeastern United States, New York City, and Washington, D.C., from 1962 to 1988. The patterns identified are interpreted in terms of the spatial behavior of measles epidemics in the region, and the implications of the methodology for surveillance and control are considered. PMID- 1442723 TI - Prevalence and incidence of viral hepatitis in health workers in the prehepatitis B vaccination era. AB - To assess the impact of hepatitis B virus on health workers, the authors studied baseline prevalences of hepatitis B serologic markers and undertook prospective surveillance to assess hepatitis B attack rates in 837 health workers and 994 blood-donor controls between 1977 and 1982, before the introduction of hepatitis B vaccine. The baseline prevalence of all hepatitis B markers was 14% in health workers and 6% in controls (p < 0.001); exposure to hepatitis B virus was related to the intensity of blood exposure and its duration. In contrast, the frequency of exposure to hepatitis A virus, a nonblood-borne agent, was lower in health workers (11%) than in controls (16%) (p < 0.01) and increased as a function of age. Multivariate logistic regression analysis identified occupational categories with frequent blood contact, rather than duration of exposure, as being the dominant variable for exposure to hepatitis B virus; for hepatitis A virus exposure, age was the most significant variable. Among health workers susceptible to hepatitis B, the incidence of new definite hepatitis B infections was 1.0% per year in 362 health workers (804 person-years of follow-up observation) with frequent blood contact versus 0% per year in 258 health workers (534 person-years of observation) with limited blood contact (p = 0.017). For definite plus probable cases combined, the incidence of new hepatitis B infections was 1.5% per year versus 0.2% per year for the groups with frequent and limited blood exposures, respectively (p = 0.0013). There were no new cases of hepatitis A or B or seroconversions in controls and only one case of hepatitis A acquired outside the hospital by a health worker. These data confirm the high prevalence of hepatitis B exposure and document in a prospective study the high incidence over time of new hepatitis B virus infections in health workers unprotected by vaccination. Such findings reiterate the need for aggressive vaccination programs in health workers exposed to blood. PMID- 1442724 TI - A foodborne outbreak of gastroenteritis involving two different pathogens. AB - On the evening of October 10, 1990, many of the 474 inmates of a state prison in Florida began to experience symptoms of gastroenteritis. An investigation included interviews with inmates, evaluation of the kitchen and food-handling practices, cultures of leftover food, stool cultures, and cultures from the nares and skin lesions of food handlers. Of the 331 inmates interviewed, 215 (65%) had diarrhea, vomiting, or both. The median incubation period was 5 hours (range, 1 41 hours). Cases with onset of illness 8 or more hours after the evening meal were more likely than those with earlier onset to have had only diarrhea without vomiting (p < 0.001). Eating turkey at the evening meal on October 10 was associated with risk of illness (relative risk = 4.8, 95% confidence interval 1.7 13.7). Cases who became ill within 8 hours of the evening meal and those who became ill later were both more likely to have eaten turkey than those who did not become ill (p < 0.001 and p < 0.007, respectively). Salmonella infantis and enterotoxin-producing Staphylococcus aureus were both isolated from samples of leftover turkey, and S. infantis was isolated from 18 of 20 stool specimens. Cultures of the anterior nares and skin lesions of food handlers grew S. aureus, but phage typing failed to link these strains to the outbreak. Improper food handling practices contributed to the development of this outbreak. This report highlights the importance of recognizing multiple-organism outbreaks, since the authors' recommendations for prevention of more cases depended upon knowing the risks associated with the distinct organisms and the possible sources of contamination. PMID- 1442725 TI - Re: "Homicide and the prevalence of handguns: Canada and the United States, 1976 to 1980". PMID- 1442726 TI - Re: "Homicide and the prevalence of handguns: Canada and the United States, 1976 1980". PMID- 1442727 TI - Re: "Homicide and the prevalence of handguns: Canada and the United States, 1976 1980". PMID- 1442728 TI - Re: "Homicide and the prevalence of handguns: Canada and the United States, 1976 80". PMID- 1442729 TI - Preexisting lung disease and lung cancer among nonsmoking women. AB - Preexisting lung disease was examined as a risk factor for lung cancer in a population-based, case-control study of nonsmoking women in Missouri conducted between June 1, 1986, and April 1, 1991. A history of lung disease was reported by approximately 41% of 618 cases and 35% of 1,402 controls (odds ratio (OR) = 1.2; 95% confidence interval (Cl) 1.0-1.5. The risk was more pronounced when next of-kin interviews were excluded (OR = 1.5). Previous lung disease was significantly related both to adenocarcinoma (OR = 1.4), which accounted for 62% of the cancers, and to all other cell types of lung cancer combined (OR = 1.8). Despite having discontinued smoking for more than 15 years, long-term ex-smokers were at a 2.2-fold risk of lung cancer compared with lifetime nonsmokers. Among lifetime nonsmokers, significant risks were noted for asthma (OR = 2.7) and pneumonia (OR = 1.5). Emphysema (OR = 2.6) and tuberculosis (OR = 2.0) were also significantly related to lung cancer, but only among former smokers. Chronic bronchitis was linked to elevated risks of nonadenocarcinomas only (OR = 2.3). Pleurisy was not reported more frequently by cases than by controls. Approximately 16% of all lung cancers among nonsmoking women could be attributed to previous lung diseases, most notably asthma, pneumonia, emphysema, and tuberculosis. PMID- 1442730 TI - Longitudinal prediction of adult blood pressure from juvenile blood pressure levels. AB - The link between blood pressure measured at juvenile ages (3-18 years) and subsequent adult ages (30 and 50 years) was investigated in a community-based longitudinal study conducted in the San Francisco Bay Area from 1928 to the present. The original sample of 550 persons decreased 61 percent by age 50 years, leaving only 211 persons in the cohort. Blood pressure was measured annually up to age 18 years and each decade thereafter, providing a unique opportunity to link childhood and adult blood pressures over periods of up to 50 years. Juvenile blood pressure measured from age 6 years onward was a positive predictor of blood pressure at age 30 years. Blood pressure measured at age 50 years was predicted best by juvenile pressures measured at early school age and early puberty. The juvenile-adult blood pressure association was partly explained by controlling for smoking and parental history of cardiovascular disease, but was not explained by controlling for juvenile height or body mass. It was stronger in children from blue collar families. The reported correlations probably represent an underestimation of the true strength of the association because of a greater loss to follow-up among subjects with higher blood pressure and the effects of antihypertensive medication in adulthood. PMID- 1442731 TI - Mortality trends in a cohort of homosexual men in New York City, 1978-1988. AB - Trends in mortality related to infection by human immunodeficiency virus type 1 (HIV-1) and to other causes were examined from 1978 to 1988 in a cohort of 8,906 homosexual men who participated in studies of hepatitis B virus infection in the late 1970s in New York City. HIV-related mortality rates increased from 1 per 10,000 person-years in 1980 to 181 per 10,000 person-years in 1986, followed by a plateau from 1986 to 1988. The standardized mortality ratio among white men in the cohort was 3.7 (95% confidence interval (Cl) 3.4-3.9) as compared with white men from across the United States. Higher HIV-related mortality rates were associated with a higher number of sexual partners, a history of gonorrhea and/or syphilis, and serologic markers of infection with hepatitis B virus. After adjustment for demographics and sexual behaviors, the relative risk of mortality for Hispanic men as compared with white men was 1.5 (95% Cl 1.1-1.9). This study illustrates the large excess in mortality among homosexual men over the last decade, with the excess accounted for by deaths from HIV-related diseases. The recent plateau in mortality may be due to the effect of new treatments and/or the decline in new HIV-1 infections among homosexual men. The excess in HIV-related mortality among Hispanic homosexual men was not explained by differences in demographics and factors associated with the sexual transmission of HIV-1. PMID- 1442732 TI - Characteristics of mothers of live infants with congenital syphilis in Florida, 1987-1989. AB - The incidence of congenital syphilis in Florida increased sixfold from 1985 through 1989, and more than 80% of the cases occurred in metropolitan areas of southern Florida. To characterize the population of pregnant women in Florida at high risk of delivering an infant with congenital syphilis, the authors conducted a case-control study using birth certificates. Birth certificates were obtained for 256 of the 344 live infants reported as having congenital syphilis from 1987 through 1989 (74%); the 246 of these infants born in hospitals were matched for hospital and week of birth with an equal number of controls. In conditional multiple logistic regression, the following maternal characteristics were independent risk factors for congenital syphilis: young age, black race, single marital status, absence of a father's name on the birth certificate, previous pregnancy, substance abuse, and lack of prenatal care. Although the national origin of the mother was not a significant risk factor, the infants of black mothers born in the United States were at greater risk than the infants of black mothers born outside the United States. Mothers who had < or = 3 prenatal visits had an increased risk of delivering an infant with congenital syphilis as compared with mothers who had > 3 visits. This study suggests that targeted outreach efforts are necessary to control congenital syphilis and provides guidance for public health intervention activities. PMID- 1442733 TI - Comparative behavioral epidemiology of gonococcal and chlamydial infections among patients attending a Baltimore, Maryland, sexually transmitted disease clinic. AB - Between April 1988 and May 1989, 400 males and 400 females attending a Baltimore, Maryland, sexually transmitted disease clinic were enrolled in a study evaluating and comparing behaviors associated with culture-proven gonococcal or chlamydial infection. The subjects were enrolled consecutively, and were all seen by the same clinician. Among participants of each sex, gonorrhea but not chlamydia was associated with increasing numbers of recent (the past 30 days) sexual partners. Compared with males with neither infection, factors independently associated with increased risk of gonorrhea included age less than 20 years (odds ratio (OR) = 1.93), the presence of genitourinary symptoms (OR = 8.07), and recent exposure to a new sexual partner (OR = 2.78); risk for chlamydial infection in males was associated with genitourinary symptoms (OR = 2.83) and was significantly reduced in those reporting multiple recent (OR = 0.19) or new (OR = 0.07) sexual partners. Among females, age less than 20 years was independently associated with gonococcal (OR = 1.86) and chlamydial (OR = 7.79) infections in comparison with females with neither infection. No other behavioral factors were associated with chlamydial infection for females in this study; however, having a regular sexual partner was associated with significantly elevated risk of gonorrhea (OR = 3.85), while the presence of genital tract symptoms was associated with diminished risk (OR = 0.29) for gonorrhea. These data suggest that there are differences in the behaviors associated with gonorrheal and chlamydial infections and that different strategies may be useful in efforts to control these infections. PMID- 1442734 TI - Behavioral risk factors for injury among rural adolescents. AB - This 3-year, longitudinal, prospective study examined behavioral risk factors for medically attended injuries among a cohort of 758 rural students from Maryland's Eastern Shore region who were 12-14 years of age in 1987. Students were surveyed annually in the eighth, ninth, and tenth grades with a self-administered questionnaire. Information was obtained on the number of injuries experienced, risk-taking behaviors, delinquency, alcohol and drug use, physical exercise and sports, parental supervision, and work experience. Information on the parents' education was obtained from a parental interview. Slightly more than half (53.5%) of the students reported having experienced one or more injuries in the eighth grade as compared with one-third of the students in ninth grade, and 38% of those in the tenth grade. Poisson regression analyses were conducted to examine the association of eighth grade variables with ninth grade injuries and ninth grade variables with tenth grade injuries. Results from these analyses indicated that, in addition to sex and race, a high degree of risk taking, frequent cruising, and having high and low parental supervision in the eighth grade significantly increased the number of injuries in ninth grade. In the tenth grade, risk taking continued to be associated with injuries. In addition, students who reported disciplinary problems in school, working 1-10 hours per week, drinking on 1-2 days during the past month, lifetime use of marijuana equal to 1-5 occasions, and involvement in sports experienced greater numbers of injuries in the tenth grade. PMID- 1442735 TI - Weight loss and mortality in a national cohort of adults, 1971-1987. AB - Although obesity is a risk factor for mortality, evidence that weight loss improves survival is limited. The relation between self-reported previous maximum weight, weight loss, and subsequent mortality was examined in 2,140 men and 2,550 women aged 45-74 years who participated in the First National Health and Nutrition Examination Survey (1971-1975) and survived the next 5 years. Vital status was determined through 1987. Among men and women whose maximum body mass index (weight (kg)/height (m)2) was between 26 and 29, risk of death increased with increasing weight loss, after adjustment for age, race, smoking, parity, preexisting illnesses, and maximum body mass index. Subjects who lost 15% or more of their maximum weight had over twice the mortality risk of those who lost less than 5%. At maximum body mass indices of 29 or higher, mortality risk increased with the amount of weight lost in women, but weight loss of 5% to < 15% appeared to lessen mortality risk in men. Generalization from these results is limited by the older age range of the sample and the inability to adequately distinguish voluntary from involuntary weight loss in this study. However, these findings suggest that prevention of severe overweight may be more generally effective than weight loss in reducing obesity-related mortality in the US population. PMID- 1442736 TI - Performance of two general job-exposure matrices in a study of lung cancer morbidity in the Zutphen cohort. AB - Data from a general population cohort of 878 men from the town of Zutphen, The Netherlands, were used to evaluate the performance of two general job-exposure matrices. Exposures generated by the job-exposure matrices on the basis of job histories were compared. The validity of those exposures was measured against exposures reported by the participants in 1977/1978. The performance of the different exposure measures was assessed in proportional hazards analyses of lung cancer morbidity incidence. The two general job-exposure matrices generally disagreed with regard to exposure classification because of differences in exposure assessment and level of detail of the job axis. When compared with self reported exposures, the sensitivity of both job-exposure matrices was low (on average, below 0.51), while the specificity was generally high (on average, above 0.90). Self-reported exposures to asbestos, pesticides, and welding fumes showed elevated risk ratios for lung cancer which were absent for exposures generated by the two job-exposure matrices. Thus, a population-specific job-exposure matrix is proposed as an alternative to general job-exposure matrices developed elsewhere. Such a matrix can be constructed from the results of in-depth interviews of a job stratified sample of cohort members. Sound validation and documentation of exposure assessment methods used in job-exposure matrices are recommended. PMID- 1442737 TI - Proxy respondents and the validity of occupational and other exposure data. The Selected Cancers Cooperative Study Group. AB - As part of a multicenter cancer case-control study conducted in 1984-1988, a proxy interview was attempted for all cases who were initially interviewed for the study but who died during the 4-year data collection period. To assess the validity of using wives, other relatives, or other informants to obtain information about a subject, the authors compared occupational and other exposure data obtained from 270 male cancer cases and their proxy respondents. The primary focus of the case-control study was on Vietnam military service and exposure to phenoxy herbicides, but cases and their proxy respondents were also asked about occupational and other exposures relevant to the cancers. The accuracy of reporting for specific occupational exposures (e.g., asbestos and formaldehyde) and specific occupations (e.g., dry cleaning and meat packing or processing) was poor, although the latter improved somewhat when only case-spouse pairs were examined. Similarly, there was poor sensitivity in the reporting of herbicide exposure information in farming and other related occupations. In contrast, the reporting of certain demographic characteristics, childhood history characteristics, and use of alcohol and cigarettes was relatively good, and was even better when only case-spouse pairs were examined. The poor quality of proxy information for detailed exposure information suggests the need for careful use and interpretation of proxy information in epidemiologic studies. PMID- 1442738 TI - Computation of relative risk based on simultaneous surveys: an alternative to cohort and case-control studies. AB - If the same information on the distribution of risk factors is available for both the general population and a subset distinguished by some disease outcome, it becomes possible to derive relative risk estimates applicable to the entire population with the assurance that the data upon which the estimates are based is representative of that population. To illustrate this approach, data from the 1986 National Mortality Follow-back Survey and the 1987 National Health Interview Survey were used to compute rate ratios for several causes of death for work in dirtyier as compared with cleaner occupations by three methods commonly employed in cohort and case-control studies: the usual standardized rate ratio, the Mantel Haenszel estimate of the rate ratio, and a multiplicative model fit to an appropriate cross-classification. Properly placed questions in appropriate surveys might very well serve as a substitute for cohort studies and could be performed at less cost and with less overall effort, and completed in a shorter time. Moreover, this approach is less subject to problems of representativeness than cohort and case-control studies. PMID- 1442739 TI - The analysis of regional patterns in health data. I. Distributional considerations. AB - Regional patterns of health data such as cancer incidence rates are often examined for evidence of environmental effects. In this paper, three measures of spatial clustering are evaluated for use with epidemiologic data. In particular, the effects of variation in regional population structure on the distribution of these measures is considered. It is shown that substantial bias occurs if variation in regional population size is ignored (as has occurred in previous analyses). On the other hand, the methods are robust to small case frequencies and to variation in the regional age distribution. It is recommended that these regional differences be routinely taken into account, which can be done with relatively little additional computation. A companion paper (Walter SD. The analysis of regional patterns in health data. II. The power to detect environmental effects. PMID- 1442740 TI - The analysis of regional patterns in health data. II. The power to detect environmental effects. AB - Three measures of spatial clustering (Moran's I, Geary's c, and a rank adjacency statistic, D) were evaluated for their power to detect regional patterns in health data. The patterns represented various environmental effects: a latitude gradient; residence near a contaminated water supply; disease "hot spots"; relation to socioeconomic status and urbanization; and general spatial autocorrelation. While the methods had high power to detect certain patterns, they were also affected by factors such as the shape of the map, its regional structure, and the spatial distribution of explanatory variables. The power was sometimes low, even for strong geographic trends, particularly for D. Moran's I had the highest power most often. We conclude that use of these methods requires careful specification of the anticipated geographic pattern and awareness of idiosyncratic effects in the study of particular maps. PMID- 1442741 TI - Re: "Repeat measurement of case-control data: correcting risk estimates for misclassification due to regression dilution of lipids in transient ischemic attacks and minor ischemic strokes". PMID- 1442742 TI - Re: "Very low birth weight: a problematic cohort for epidemiologic studies of very small or immature neonates". PMID- 1442743 TI - Epidemiology of the post-polio syndrome. AB - A late-onset syndrome, consisting of muscle weakness, muscle pain, and unaccustomed fatigue, has been reported with increasing frequency among former poliomyelitis patients. A population-based cohort of poliomyelitis patients from Allegheny County, Pennsylvania, was traced and surveyed to estimate the prevalence and incidence and to identify determinants of the post-polio syndrome. A questionnaire validated in clinical examinations of 40 cohort members was used in the survey. The prevalence of the post-polio syndrome was 28.5% of all paralytic cases (95% confidence interval 24.4-32.6). The risk of post-polio syndrome was significantly higher among patients who sustained substantial permanent impairment after polio and among females. The incidence did not vary with age at acute onset, acute severity, or level of physical activity after recovery. The strongest determinant of post-polio syndrome onset was the length of the interval following the acute illness, with incidence peaking at 30-34 years. Of all cases of post-polio syndrome, 79% reported no major change in impairment status since onset. This study demonstrates that poliomyelitis patients are not equally susceptible to post-polio syndrome within the interval of 30-40 years after the original illness. For syndrome cases, the onset was associated with new neuromuscular symptoms and functional changes but not with major new impairment. PMID- 1442744 TI - Prevalence of gallstone disease in relation to smoking, alcohol use, obesity, and glucose tolerance: a study of self-defense officials in Japan. AB - Risk factors of gallstone disease were investigated in male self-defense officials who received, between October 1986 and December 1990, a retirement health examination at the Self-Defense Forces Fukuoka Hospital, Fukuoka, Japan. Gallbladder ultrasonography, successfully performed with 2,739 of 2,756 men, found 61 men with gallstones and 38 men with previous removal of the gallbladder; the overall prevalence of gallstone disease was 3.6%. Multiple logistic regression analysis assessed the risk of gallstone disease in relation to smoking, alcohol use, body mass index, glucose tolerance, and rank. Alcohol use was associated with a decreased risk, and body mass index was positively related to gallstone disease. Men with impaired glucose tolerance had a slightly elevated risk, whereas diabetes mellitus was not associated with gallstone disease. Analysis for prevalent gallstones and the postcholecystectomy state showed an inverse association of alcohol use with the latter; a positive association with impaired glucose tolerance was also confined primarily to the latter condition. These findings provide little support for a protective effect of alcohol use in the formation of gallstones. It was inconclusive whether impaired glucose tolerance was associated selectively with postcholecystectomy. PMID- 1442745 TI - Blood pressure reactivity does not correlate with baseline blood pressure or blood pressure change over time in preschool children. AB - Few studies have examined the relation of blood pressure reactivity to subsequent change in blood pressure of preschool children. The authors investigated relations between measurement-induced reactivity, exercise reactivity, and change in blood pressure over 16 months among 140 preschool children (46-67 months of age at baseline, 50.7% female, 92.9% Hispanic). Within-session measurement induced reactivity was defined as the change in blood pressure between the first and the mean of the fourth and fifth readings obtained at each of 11 sessions. Between-session measurement-induced reactivity was defined as the change between mean blood pressure at session 1 and the mean of sessions 2 and 3. Both indices of measurement reactivity displayed poor reproducibility. Exercise reactivity was measured using a treadmill on two occasions and was moderately reproducible. There was no association between measurement and exercise reactivity. The change in systolic blood pressure over time was not associated with any measure of reactivity. The mean diastolic blood pressure did not change over the study period. Neither blood pressure reactivity to measurement nor blood pressure reactivity to exercise appeared to be a useful predictor of change in blood pressure in preschool children during a 16-month period. PMID- 1442746 TI - Physical activity and serum lipids: a cross-sectional population study in eastern Finnish men. AB - The authors studied the association of the type, amount, and intensity of physical activity with serum lipids in 2,492 randomly selected eastern Finnish men aged 42-60 years during 1984-1989, controlling for the major confounding factors. High density lipoprotein cholesterol (HDL cholesterol) and HDL2 cholesterol were associated positively and triglycerides inversely with total, occupational, and leisure time activity in a multivariate regression model (p < 0.001). HDL3 cholesterol was associated positively only with total activity (p < 0.001). The adjusted relative differences in HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, and triglycerides between extreme total (occupational, leisure time) activity quartiles were 10.7% (9.0%, 5.7%), 12.2% (10.3%, 9.5%), 5.9% (2.9%, 0%), and 22.7% (9.2%, 10.4%), respectively. HDL cholesterol and HDL2 cholesterol were the highest and triglycerides the lowest at a conditioning activity intensity of more than 6 metabolic units (p < 0.001). The strongest associations were found for the 24-Hour Recording, which suggests short-term effects of physical activity on serum lipids. The beneficial effects of physical activity on serum lipids appear to be mediated partially by a reduced serum insulin concentration and decreased body adiposity. These data provide further confirmation for the concept that both regular or at least moderate intensity leisure time activity and occupational physical activity have a favorable impact on serum lipids. PMID- 1442747 TI - Does recent alcohol consumption reduce the risk of acute myocardial infarction and coronary death in regular drinkers? AB - This study, conducted in Auckland, New Zealand, over 2 years from March 1986, used a case-control design to investigate the hypothesis that alcohol acutely increases the risk of both nonfatal myocardial infarction and coronary death in the 24 hours after drinking, among regular drinkers. The nonfatal myocardial infarction analyses included 278 male and 60 female cases identified from a population-based coronary heart disease surveillance program and 458 male and 266 female controls randomly selected from the same population matched by age and sex. In the coronary death analyses, 172 male and 16 female coronary death cases from the same surveillance program and a population-based sample of 294 males and 165 females who were age and sex matched were examined. Information on alcohol consumption in the 24 hours before the coronary event in cases and a comparable 24-hour period in controls was collected. Study subjects all drank alcohol regularly at least once per month and were aged 25-64 years. Controls were more likely than cases to report a drinking episode in the 24-hour period examined in both sexes and for fatal and nonfatal disease. After controlling for possible confounding, the authors found that drinkers had a consistently lower estimated risk of both fatal and nonfatal coronary heart disease than participants reporting no alcohol in the previous 24 hours. The odds ratios ranged from 0.75 (95% confidence interval 0.62-0.90) for nonfatal myocardial infarction in men to 0.46 (95% confidence interval 0.19-1.10) for coronary death in women. There were no clear differences in estimated acute risk among those who drank one or two drinks, three or four drinks, or more than four drinks in the 24-hour period. These findings suggest that, contrary to previous speculation, alcohol consumption may acutely reduce coronary heart disease risk. PMID- 1442748 TI - Comparison of long-term dietary recall between cancer cases and noncases. AB - A quantitative history of current dietary intake based on 83 food items was administered by interview to a representative sample of 4,809 subjects in Hawaii in 1977-1979. In 1983-1987, this history was readministered to the 131 original respondents who had subsequently developed cancer, as well as 413 randomly selected subjects who remained cancer free. A surrogate was interviewed when the original subject was unavailable. The repeat interview elicited information about diet at the time of the original interview. The authors found that recall values for macronutrients were consistently higher than original levels for both cases and noncases, which may be due in part to a modification in the administration of the repeat questionnaire. Although there were no marked differences overall between cases and noncases in the ability to recall past diet, differences between the two groups were seen in certain subsets of the sample. In the subgroup with the longest recall interval (8-10 years), cases were not able to recall their diets as well as noncases. Also, the difference between original and recall values was larger for cases with colorectal cancer and all cases diagnosed with distant stage disease, compared with noncases. This was not true for cases of breast and prostate cancer and those with localized or regional disease. The following variables were found to have no significant effect on recall for cases or noncases: sex, age, education, and type of respondent (surrogate or subject). Of the five major ethnic groups included in the study, Japanese had the best recall of their past diets, while respondents reporting a diet change between the interviews had poorer recall than did those who reported no change. These results suggest that differential misclassification in dietary case-control studies may pose a significant problem in certain instances, but that these studies can yield meaningful results with certain constraints on the study population. PMID- 1442749 TI - Cancer of the pancreas and drinking water: a population-based case-control study in Washington County, Maryland. AB - A case-control study was done to assess a potential association between drinking water and pancreatic cancer in Washington County, Maryland. Cases of pancreatic cancer occurring from 1975 through 1989 were identified from the cancer registry. Controls were selected from the private 1975 census of Washington County. There were 101 cases and 206 controls. Chlorinated municipal water was used as a source of drinking water by 79% of cases and 63% of controls, yielding a significant odds ratio of 2.2. Adjustment for age and smoking had almost no effect on the risk, although both age and smoking were independently associated with an increased risk of pancreatic cancer. Although these findings must be interpreted with caution because of limitations in exposure assessment, these results have implications for the prevention of pancreatic cancer because chlorination of water is so widely practiced. PMID- 1442750 TI - Lymphohematopoietic cancer in styrene-butadiene polymerization workers. AB - 1,3-Butadiene and styrene are suspected carcinogens and common chemicals used in the synthesis of rubber. To investigate any potential human hazards from exposure to these chemicals, a case-control study of 59 lymphohematopoietic cancers was conducted within a cohort of male workers employed between 1943 and 1982 in eight North American styrene-butadiene rubber polymer-producing plants. A total of 193 controls were matched to the cases by plant, age, year of hire, duration worked, and survival to time of death of the case. Each job was assigned an estimated exposure rank, and each worker's cumulated rank score was calculated on the basis of the time spent in each job throughout his employment. "Exposure" as a dichotomous variable was defined as a log rank score above the mean of the log scores for the total population of cases and controls within a subtype of cancer. Matched-pair analysis identified a strong association between leukemia and butadiene, with an odds ratio of 9.36 (95% confidence interval 2.05-22.9) and an association between styrene and leukemia (odds ratio = 3.13, 95% confidence interval 0.84-11.2) that did not achieve statistical significance. When exposure to both styrene and butadiene was included in a conditional logistic regression model, the odds ratio for butadiene remained high (odds ratio = 7.39), but the estimated association of leukemia with styrene was small. The results of this study support the hypothesis that exposure to butadiene is associated with the risk of leukemia. There also appears to be an additional risk from work in specific subdivisions of the industry. PMID- 1442751 TI - Use of multiple-cause mortality data in epidemiologic analyses: US rate and proportion files developed by the National Institute for Occupational Safety and Health and the National Cancer Institute. AB - The authors have created US mortality rates (age, sex, race, and calendar-time specific) and proportions, using multiple cause-of-death data, for the years 1960 1989. Multiple cause-of-death data include the usual underlying cause of death from the death certificate as well as contributory causes and other significant conditions. US multiple-cause rates and proportions enable the user to calculate the expected occurrences of disease on the death certificates of a cohort under study. There is an average of 2.66 causes and/or contributory conditions listed on US death certificates, increasing over time from 2.54 in the 1960s to 2.76 in the 1980s. The ratio of multiple-cause listings to underlying cause listings varies by disease, from low ratios for cancers to high ratios for diseases such as diabetes, arthritis, prostate disease, hypertension, pneumoconiosis, and renal disease. Use of these data is illustrated with two cohorts. Multiple-cause analysis (but not underlying cause analysis) revealed twofold significant excesses of renal disease and arthritis among granite cutters. For workers exposed to dioxin, neither multiple-cause nor underlying cause analysis indicated any excess of diabetes, an outcome of a priori interest. Good candidates for multiple-cause analysis are diseases that are of long duration, not necessarily fatal, yet serious enough to be listed on the death certificate. PMID- 1442752 TI - Unspecified injuries on death certificates: a source of bias in injury research. AB - Protective gear (for example, helmets and bulletproof vests) shields certain body regions from damaging energy. Failure to specify on death certificates the body region and nature of fatal injuries compromises the utility of mortality data for epidemiologic or prevention research. Of fatally injured California motorcyclists, 41% had no specific injuries listed on their death certificates in 1988. To examine the implications of this problem, the authors abstracted 186 coroner's or medical examiner's reports from four California counties with over 60% nonspecific injuries and one county with few such injuries. These data were merged with computerized death certificate files and with the Fatal Accident Reporting System. Among the 99 cases with nonspecific injury codes, 68% had head injuries, 63% had chest injuries, 58% had abdominal injuries, and 58% had extremity injuries. Reporting sensitivity in the four problem counties varied from 36% for head injury to less than 5% for abdominal, spinal, and extremity injury. The association between head injury and failure to wear a helmet was statistically significant using the coroner's diagnoses (p = 0.02), but not using death certificate diagnoses (p = 0.17). The value of mortality data to injury researchers would be enhanced by better reporting of the nature of injury on death certificates. PMID- 1442753 TI - Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. AB - To determine whether commonly used psychoactive drugs increase the risk of involvement in motor vehicle crashes for drivers > or = 65 years of age, the authors conducted a retrospective cohort study. Data were obtained from computerized files from the Tennessee Medicaid program, driver's license files, and police reports of injurious crashes. Cohort members were Medicaid enrollees 65-84 years of age who had a valid driver's license during the study period 1984 1988 and who met other criteria designed to exclude persons unlikely to be drivers and to ensure availability of necessary study data. There were 16,262 persons in the study cohort with 38,701 person-years of follow-up and involvement in 495 injurious crashes. For four groups of psychoactive drugs (benzodiazepines, cyclic antidepressants, oral opioid analgesics, and antihistamines), the risk of crash involvement was calculated with Poisson regression models that controlled for demographic characteristics and use of medical care as an indicator of health status. The relative risk of injurious crash involvement for current users of any psychoactive drug was 1.5 (95% confidence interval (CI) 1.2-1.9). This increased risk was confined to benzodiazepines (relative risk = 1.5; 95% CI 1.2-1.9) and cyclic antidepressants (relative risk = 2.2; 95% CI 1.3-3.5). For these drugs, the relative risk increased with dose and was substantial for high doses: 2.4 (95% CI 1.3-4.4) for > or = 20 mg of diazepam and 5.5 (95% CI 2.6-11.6) for > or = 125 mg of amitriptyline. Analysis of data for the crash-involved drivers suggested that these findings were not due to confounding by alcohol use or driving frequency. PMID- 1442754 TI - Depressive symptoms and other psychosocial factors as predictors of stroke in the elderly. AB - The aim of this paper is to assess the influence of selected psychosocial factors as predictors of stroke incidence in a probability sample of noninstitutionalized elderly. The main psychosocial factor of interest was depression. Marital status, social support, social networks, and religiousness were also assessed as potential antecedent or mediating factors. The data were obtained from a prospective longitudinal study based on 2,812 individuals aged 65 years and over living in New Haven, Connecticut. The incidence of stroke was monitored from the baseline interview in 1982 until December 1988. Depression, measured by the Center for Epidemiologic Studies Depression Scale (CES-D), was measured at baseline as were other predictor variables. Univariate Cox regression analyses revealed that higher CES-D scores were predictive of greater stroke incidence (p < 0.05). More frequent attendance at religious services was associated with lower incidence (p < 0.001). CES-D scores were also correlated with many measures of sociodemographic, health, and physical function factors in our multivariate analysis (p < 0.05). When combined with other significant predictor variables such as age, sex, hypertension, diabetes, physical function, and smoking, neither depression nor religious attendance retained its significance. PMID- 1442755 TI - Prevalence and risk determinants of human immunodeficiency virus type 2 (HIV-2) and human immunodeficiency virus type 1 (HIV-1) in west African female prostitutes. AB - The authors studied the prevalence and risk determinants for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in female prostitutes from Dakar (1985-1990), Ziguinchor (1987-1990), and Kaolack (1987-1990), Senegal, West Africa. Each cohort showed a distinct distribution of HIVs: 10.0% HIV-2 and 4.1% HIV-1 in Dakar, 38.1% HIV-2 and 0.4% HIV-1 in Ziguinchor, and 27.4% HIV-2 and 1.3% HIV-1 in Kaolack. In 1,275 female prostitutes from Dakar, increase years of sexual activity and a history of scarification were associated with HIV-2 seropositivity. In contrast, HIV-1 seroprevalence was associated with a shorter duration of prostitution and a history of hospitalization. In 278 female prostitutes from Ziguinchor, HIV-2 seroprevalence was associated with women of Guinea-Bissau nationality and increased years of sexual activity. In 157 female prostitutes from Kaolack, HIV-2 seroprevalence was associated with increased years of sexual activity and a history of never using condoms. The authors also studied the risk determinants for HIV-2 in the 1,280 Senegalese prostitutes pooled from all three sites. Controlling for ethnic group, women from Ziguinchor and Kaolack were more likely to be HIV-2 seropositive as compared with women from the Dakar site. Increased years of sexual activity were associated with HIV-2 seropositivity, while a history of excision and BCG vaccinations decreased the risk of HIV-2 infection. PMID- 1442756 TI - The kidney in hypertensive pregnancies--victim and villain. AB - Many changes in renal function occur in normal pregnancy. Without a proper understanding of these changes, routine clinical investigations may easily be misinterpreted. Women with preeclampsia have further alterations in renal function and, in occasional cases, develop acute renal failure. Understanding of abnormal renal physiology and hormonal changes in these women allows the clinician to interpret biochemical tests appropriately and make proper use of vasodilator therapy with careful attention to volume homeostasis. Women who undertake pregnancy with a primary renal disease, most commonly glomerulonephritis or reflux nephropathy, have a higher risk of adverse fetal and maternal outcomes. Awareness of these risks provides a basis for proper preconceptual counseling, as well as careful monitoring of maternal blood pressure and renal function and fetal growth during such pregnancies. These strategies will optimize the chances of a successful pregnancy outcome for both mother and baby. PMID- 1442757 TI - A randomized, double-blind, placebo-controlled trial to evaluate the effect of enalapril in patients with clinical diabetic nephropathy. AB - It is unknown if the antiproteinuric effect of angiotensin-converting enzyme (ACE) inhibitors reflects attenuation in the rate of progression of diabetic nephropathy. We report the results of a randomized, double-blind clinical trial designed to evaluate the longitudinal (18-month) effect of the ACE inhibitor, enalapril (5 to 40 mg/d), versus a placebo on 24-hour urinary protein excretion and on the rate of progression of renal disease in 33 patients with clinical diabetic nephropathy. Systemic blood pressure was controlled throughout the trial with conventional antihypertensive drugs. Glomerular filtration rate (GFR), determined by Tc99mDTPA renal clearance, and urinary protein excretion were monitored at 3-month intervals. Enalapril, in contrast to placebo therapy, was associated with an initial (40%) and sustained (33%) decrease in urinary protein excretion. Patients randomized to both enalapril or placebo experienced mean decreases in GFR, from 1.01 mL/s/1.73 m2 (61 mL/min/1.73 m2) to 0.85 mL/s/1.73 m2 (51 mL/min/1.73 m2), and from 1.06 mL/s/1.73 m2 (64 mL/min/1.73 m2) to 0.97 mL/s/1.73 m2 (58 mL/min/1.73 m2), respectively. Eleven of 18 patients (61%) randomized to enalapril, and 10 of 15 (66%) patients randomized to placebo, had a decrease in GFR; their rates of progression were -1.18 mL/min/1.73 m2/mo and 1.00 mL/min/1.73 m2/mo, respectively. In the absence of changes in blood pressure, the addition of an ACE inhibitor to patients with clinical diabetic nephropathy could not be shown to confer a unique renal protective effect. A prolonged decrease in 24-hour protein excretion could not be shown to predict attenuation in the progression of established clinical diabetic nephropathy. PMID- 1442758 TI - Lupus anticoagulant in systemic lupus erythematosus: a clinical and renal pathological study. AB - Circulating lupus anticoagulant (LA) is associated with thrombosis in large and small vessels. To determine how often the presence of LA is associated with thrombosis within the renal microcirculation, 33 patients with systemic lupus erythematosus (SLE), renal dysfunction, and LA were identified over a 25-year period (LA group) and 32 patients with renal SLE but with normal gross coagulation screen were matched for age, sex, and biopsy timing (C group). Prevalences of serositis, neuropsychiatric illness, leukopenia, thrombocytopenia, hemolysis, anti-DS-DNA elevation, and complement reduction were similar. Arthritis was less and biologic false-positive (BFP) syphilis serology more common in LA. More LA patients had thrombotic events (LA 39% v C 13%; P = 0.014); bleeding episodes, including postbiopsy, were similar. At biopsy, hypertension (LA 55%, C 41%), serum creatinine (mean +/- SD: LA 186 +/- 168 mumol/L [2.1 +/- 1.9 mg/dL] v C 150 +/- 168 mumol/L [1.7 +/- 1.9 mg/dL]) and proteinuria (LA 2.6 +/- 3.1 g/24 h v C 3.1 +/- 2.7) were similar. Lesions by World Health Organization (WHO) class, activity, and chronicity indices, as well as immunofluorescence (IF) and electron microscopy (EM) findings, were not significantly different. Occlusive glomerular, arteriolar, and arterial fibrin thrombi, along with varying degrees of renal thrombotic microangiopathy, were seen in five of 33 patients with LA, but zero of 32 C patients (P = 0.053); three of these five patients died soon after biopsy. Overall, mortality was not different between LA and C. We conclude that the majority of patients with SLE, renal dysfunction, and LA exhibit renal morphologic findings indistinguishable from patients without LA. However, a significant minority of LA patients have thrombotic microangiopathy in their biopsy, which is accompanied by a worse prognosis. PMID- 1442759 TI - Short-term responsiveness of membranous glomerulopathy to cyclosporine. AB - We administered a 12-week course of cyclosporine (CsA) (4 to 6 mg/kg/24 h) to nephrotic patients with membranous glomerulopathy (MG). Nephrotic patients with minimal change nephropathy (MCN) served as a comparison group. We evaluated the effects of CsA on proteinuria, glomerular function, and the release of cytokines by peripheral blood mononuclear cells in culture. Proteinuria was restored to normal levels within 2 to 4 weeks in MCN. Proteinuria declined from nephrotic to subnephrotic levels (< 3,500 mg/24 h) in 10 of 14 patients with MG, also within 2 to 4 weeks of onset of therapy. The four nonresponders exhibited a rapidly progressive and presumably irreversible form of MG culminating in renal failure. On average, fractional clearances of albumin and IgG declined by 59% and 73% in MG (P < 0.005); corresponding declines in MCN were by 99% (P < .0001). Corresponding rates of glomerular filtration in each glomerular injury remained unchanged. A strong trend for proteinuria to relapse after CsA was withdrawn was evident in both disorders. The release of tumor necrosis factor (TNF)-alpha by mononuclear cells in culture was enhanced in each glomerular injury, both before and after the course of CsA. We conclude that the proteinuria in most cases of MG exhibits a responsiveness to CsA that is qualitatively similar to, but less complete than, that in MCN. The rapidity with which barrier function improves suggests a possible role for cell-mediated immune injury in MG. PMID- 1442760 TI - Dermal patch anesthesia: pain-free puncture of blood access in hemodialysis patients. AB - Clinical application of dermal patch anesthesia to relieve pain at venous cannulation of blood-access was studied in hemodialysis patients. Aqueous gel of 10% lidocaine base with 3% glycyrrhetinic acid monohemiphthalate disodium (GA MHPh 2Na) was applied for 60 minutes to the skin of the patients. Degree of pain was expressed as a pain score. Analgesic effect of the lidocaine gel was evaluated in 16 patients in a placebo-controlled, double-blind, cross-over design by comparing the gel with lidocaine with a placebo gel without lidocaine. The mean pin-prick pain score (1.0 +/- 0.5) in the lidocaine gel patch (n = 16) was significantly lower than that (2.3 +/- 0.3) in the placebo gel patch (P < 0.01). In 8.8% of the patients, blood pressure was elevated after venous cannulation, but this tendency was modified by dermal patch anesthesia with the lidocaine gel. Plasma concentration of lidocaine was under the detection limit of assay (< 0.05 micrograms/mL) after dermal patch anesthesia in six subsequent dialysis treatments. PMID- 1442761 TI - Fungal peritonitis in continuous ambulatory peritoneal dialysis--the Auckland experience. AB - Fungal infection is an uncommon cause of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). We report our center's experience with 38 episodes of fungal peritonitis occurring in 33 patients, out of a total of 503 patients managed on CAPD over 11 1/2 years, and review the relevant literature. Our usual management philosophy has been one of early peritoneal catheter removal without antifungal therapy. In those with worsening clinical features, and in those with persistence of signs and symptoms beyond 48 hours after catheter removal, antifungal drugs were administered. Only five patients received antifungal therapy initially, followed by later catheter removal. Seventy-six percent of patients treated by catheter removal alone (N = 21) and 64% of patients treated by catheter removal followed by antifungal therapy (N = 11) were successfully reestablished on CAPD. A policy of early catheter removal, usually alone, but followed by antifungal therapy in select cases, can be associated with a mortality rate of less than 15% and a high rate of return to effective peritoneal dialysis. PMID- 1442762 TI - Inguinal herniorrhaphy in the continuous ambulatory peritoneal dialysis patient. AB - Inguinal hernia repair in the patient on continuous ambulatory peritoneal dialysis (CAPD) is complicated in theory by an increased potential for recurrence. In addition to the constant increased intraabdominal pressure, chronic renal failure has been shown to impair tissue healing. Controversy exists regarding the waiting period before resuming CAPD postoperatively. A retrospective review of all CAPD patients undergoing inguinal herniorrhaphy was performed. The patient's age, type of repair, duration of renal failure preoperatively, length of time on CAPD postoperatively, and date of resumption of CAPD were recorded. An inpatient and outpatient chart review was performed on all patients. Telephone follow-up was performed on surviving patients. From April 1981 to June 1989, 30 patients underwent 36 inguinal herniorrhaphies while on CAPD. One immediate postoperative death occurred due to underlying cardiac disease. The mean follow-up for surviving patients was 34 months (range, 16 to 91) and for those deceased was 25 months (range, 1 to 60). No recurrent hernias were identified either by extensive inpatient and outpatient chart review, or by direct patient telephone contact in all surviving patients. We conclude that inguinal herniorrhaphy can be safely performed in CAPD patients. Peritoneal dialysis can be initiated immediately after repair in this high-risk group of patients. There is a low risk of recurrence; however, long-term patient survival is not expected due to concurrent underlying medical problems. PMID- 1442763 TI - Fibromuscular dysplasia of the renal arteries associated with antiphospholipid autoantibodies: two case reports. AB - A relationship appears to exist between antiphospholipid autoantibodies (APLA) and vascular occlusion, although the exact mechanism is still a matter of debate. We present and comment on two cases of renal artery occlusion in patients with concomitant presence of arterial fibromuscular dysplasia and high APLA titers. PMID- 1442764 TI - Treatment of antineutrophil cytoplasmic autoantibody-positive systemic vasculitis and glomerulonephritis with pooled intravenous gammaglobulin. AB - Antineutrophil cytoplasmic autoantibody (ANCA) is considered a serological marker for disease activity in patients with ANCA(+) systemic vasculitis. Recently, ANCA has been implicated as a pathogenic antibody that may be associated with neutrophil degranulation and release of lytic enzymes. Since intravenous gammaglobulin (IVIG) is known to contain antiidiotypic antibodies to ANCA, which could decrease the activity of the later, we chose to treat two patients with symptomatic ANCA(+) systemic vasculitis and glomerulonephritis with high-dose IVIG. The first patient, a 66-year-old man, developed rapidly progressive renal failure despite treatment with intravenous (IV) cyclophosphamide. The second patient, a 14-year-old boy, had relapsed 3 months after cessation of treatment with prednisone and cyclophosphamide. Both patients improved dramatically after treatment with IVIG, with the former recovering renal function within 11 days of therapy. In both patients, a concomitant reduction in serum ANCA titers was also observed. The second patient is currently in a sustained remission 14 months after his last IVIG dose on no other medication. These cases provide clinical evidence that IVIG has therapeutic benefit in modifying the immune-mediated injury associated with ANCA(+) systemic vasculitis and glomerulonephritis. In addition, IVIG may provide an additional safe therapeutic option to clinicians treating patient's with ANCA(+) vasculitis and glomerulonephritis who are not responsive to or are experiencing toxicity from conventional therapy. PMID- 1442765 TI - Severe arteriosclerosis in the kidney of a cocaine addict. AB - Cocaine abuse has been associated with sudden cardiac death with coronary artery thrombosis with or without underlying vessel disease. Additional vascular beds thus far implicated in cocaine-associated arteriopathy include thoracic and abdominal aorta, and pulmonary, cerebral, and placental vessels; abnormalities include vasospasm, thrombosis, and accelerated atherosclerosis. We report the case of an adult male cocaine user with severe arteriosclerosis of renal vessels, and suggest that cocaine may also affect the renal vasculature. PMID- 1442766 TI - Unusual glomerular lesion in a patient receiving long-term interferon alpha. AB - A 60-year-old man with long-standing chronic myelogenous leukemia presented with renal insufficiency and proteinuria after more than 6 years of therapy with daily interferon alpha injections. He also manifested unusual skin lesions and a low titer antinuclear antibody (ANA). Percutaneous renal biopsy disclosed an unusual glomerular lesion characterized by global, diffuse, and marked widening of the lamina rara interna, and focal segmental mesangial proliferation. Discontinuation of the drug resulted in resolution of the proteinuria, but not the renal insufficiency. These glomerular changes have not been reported previously as a complication of this form of malignancy and are similar to lesions reported in newborn rats and mice receiving interferon alpha. The potential role of interferon alpha in the development of this glomerular disease is discussed. PMID- 1442767 TI - The natriuretic peptides and their receptors. AB - Atrial natriuretic factor (ANF) is released from the cardiac atrium in response to stretch and acts through receptors to cause an increase in urinary flow and sodium excretion, vasodilatation, and a reduction in blood volume. Recently, two new natriuretic peptides, brain natriuretic peptide (BNP) and C-type natriuretic peptide (C-typeNP), have been isolated, and three different natriuretic peptide receptors have been identified. Two of the receptors, ANP-RGC(A) and ANP-RGC(B), mediate biologic actions. The natural ligand of ANP-RGC(A) is ANF, whereas that of ANP-RGC(B) is C-typeNP. In view of clear differences in ligand specificity and tissue distribution of these receptors, it has been proposed that ANF and its receptor, ANP-RGC(A), and C-typeNP and its receptor, ANP-RGC(B), represent two distinct natriuretic peptide regulatory systems. Whether a separate system exists that incorporates BNP awaits clarification of its natural receptor that mediates a biologic action. The third receptor, ANP-Rc, binds all three natriuretic peptides. Its messenger RNA lacks the guanylyl cyclase sequence present in the mRNA of the other natriuretic peptide receptors, suggesting that the principal function of ANP-Rc is to remove natriuretic peptides from the circulation, that is, to regulate plasma levels of the natriuretic peptides. However, ANP-Rc may also mediate a biologic effect. These findings raise several intriguing questions about the functional role of this family of natriuretic peptides. PMID- 1442768 TI - United States Renal Data System 1992 Annual Data Report. Analytical methods: technical notes. PMID- 1442769 TI - United States Renal Data System. Policy on data release for investigator initiated research August 15, 1992. PMID- 1442770 TI - The USRDS and its database. PMID- 1442771 TI - Patient selection to peritoneal dialysis versus hemodialysis according to comorbid conditions. AB - An historical prospective sample of 2,420 non-diabetic and 1,738 diabetic Medicare patients incident from 1986-87 was analyzed for the selection of patients to peritoneal dialysis (PD) and hemodialysis (HD) according to comorbid factors. Data measuring the degree of comorbidity, describing the major diagnosis leading to end-stage renal disease (ESRD), and reporting other sociodemographic factors for incident ESRD patients were collected in a special study of the USRDS. Patients selected to PD were more likely to be white (greater mortality risk), diabetic (greater mortality risk), and younger (lower mortality risk) than patients assigned to HD. Estimates of the overall level of comorbidity with adjustment for race, gender, diabetes, and age provided evidence of a reduced total count of comorbid factors for PD compared to HD, particularly among diabetic patients under 60 years of age (p < 0.01). Assessment of selected risk factors, with adjustment for age and diabetes, indicated that patients selected to PD were not at greater comorbid risk according to cardiovascular factors but demonstrated a 20 percent increase in the likelihood of peripheral vascular disease (p = 0.02). PMID- 1442772 TI - Mortality of blacks and whites with end-stage renal disease attributed to hypertension. AB - Demographic and mortality analyses were performed for all Medicare black (26,100) and white (31,859) ESRD patients from the USRDS database who were incident between 1977 and 1988, and for whom the reported cause of ESRD was hypertension. Over the years 1977-88, the incidence rates increased markedly. The median age for both black and white incident patients also increased, while the percent of patients who were black decreased over time. Percent survival at one year and five years after onset of ESRD was significantly higher and statistically significant in black patients whose ESRD developed in the middle and older ages, compared to white patients of the same age group. PMID- 1442773 TI - Comorbid conditions and correlations with mortality risk among 3,399 incident hemodialysis patients. AB - The percent distribution of selected comorbid conditions from a national sample of 3,399 Medicare patients starting maintenance hemodialysis in 1986-87 is described. Using the Cox proportional hazards model, the relative mortality risk (RR) was assessed for comorbid conditions at time of ESRD while adjusting for the other comorbid and demographic covariates. Coronary artery disease and congestive heart failure, each present in 41 percent of patients, were associated with RR of 1.22 and 1.26 respectively (p < 0.0005 each). Fifty percent of patients had a serum albumin concentration at onset of ESRD of less than 3.5 gm/dl, and an increased risk of dying. Additionally, patients recorded as undernourished had an elevated risk (RR = 1.34, without adjustment for serum albumin, p < 0.0001). Other factors associated with a statistically significant increased mortality risk (p < 0.005) included older age, diabetes as cause of ESRD (particularly if insulin dependent), history of neoplasm, active smoker, and relatively low serum creatinine concentration. By describing the magnitude of risk associated with comorbid conditions, this study emphasizes the need for preventive efforts during the pre-ESRD stages of renal impairment. Studies are needed to document whether improvement in serum albumin or other comorbid factors before ESRD leads to reduction in mortality risk for ESRD patients. PMID- 1442774 TI - Characteristics of dialysis prescriptions in the US, 1986-1987. AB - We analyzed the dialysis prescription parameters for 4,532 randomly chosen incident Medicare patients who reached end-stage renal disease (ESRD) in 1986-87. Data were abstracted from the patient's record by the ESRD Networks. Dialysis prescription was assessed at one month following onset of ESRD. Eighty-four percent (3,823) of these patients were initially treated with hemodialysis, while the remaining 16 percent (709) were treated initially with continuous ambulatory peritoneal dialysis (CAPD). Average age for hemodialysis patients was 58, which was five years older than the average found for CAPD patients. Black patients were heavier than white patients by three kilograms, on average; black patients also had a somewhat higher body mass index. Hemodialysis prescriptions averaged 2.9 treatments per week, for a total of 9.8 hours of hemodialysis per week. Black patients had a four percent longer hemodialysis prescription (hours) per week than did white patients. Although black patients were heavier than white patients, their prescribed Kt/V was similar to that prescribed for white patients. On average, the prescribed Kt/V was 1.0. Twenty-two percent of patients had a prescribed Kt/V of less than 0.80. Compared to ESRD patients treated in the European Dialysis and Transplant Association (EDTA), the prescription for this sample of incident US hemodialysis patients was 25 percent shorter in total hours per week. Dialyzers were reused in approximately 65 percent of hemodialysis patients. CAPD patients had an average prescription of 52 liters of exchange per week with typically four exchanges per day and two liters per exchange. PMID- 1442775 TI - Catheter-related factors and peritonitis risk in CAPD patients. AB - In a national study of essentially all patients starting CAPD therapy at home during January through June, 1989 (n = 2,807), the peritonitis risk was assessed by patient demographics, connection techniques, and catheter-related factors. The present report focuses on several CAPD catheter-related factors, while adjusting for other patient and facility characteristics using Cox proportional hazards models. This study also provides a description of the actual practice, utilization, and insertion of peritoneal catheters. The relative peritonitis risk, assessed during the 10.5 to 21 month follow-up in days to first peritonitis episode, was increased for single-cuff versus double-cuff catheters (RR = 1.20, p = 0.01) and with use of intraperitoneal drugs (RR = 1.14, p = 0.08). A lateral catheter placement was associated with a reduced relative risk, but this finding deserves further study. No significant association with peritonitis risk was found for catheter design, insertion technique or operator, nor for antibiotic prophylaxis at time of catheter placement. This study defines the magnitude of relative risks in a national sample, and helps direct future work towards reducing the risk of peritonitis and/or catheter loss in CAPD patients. PMID- 1442776 TI - Mortality rate comparisons of never, previously, and currently transplanted ESRD patients. AB - Based on analysis of data for 68,683 end-stage renal disease (ESRD) patients per year (on average) prevalent between 1987-89, we report mortality rates for never (NTD) and previously (PTD) transplanted dialysis patients and for patients with a first functioning cadaveric transplant (Tx). Data are for black and white patients between the ages of 20 and 65. Using death rates for all ESRD patients as the standard and adjusting for age, race, and diagnosis, the standardized mortality ratios (SMRs) were 1.24, 1.35, and 0.37 for NTD, PTD, and Tx patients, respectively (significantly different from 1.0, p < 0.001). In a direct comparison between NTD and PTD patients, the mortality rate among PTD patients was typically 91 percent (p < 0.001) of the rate among NTD patients, although the size of the ratio varied by race, being 81 percent (p < 0.001) and 96 percent (ns) for black and white patients, respectively. This indicates that part of the reduction in mortality among transplant patients relative to dialysis patients might be attributable to selection of healthier patients for transplant, since PTD patients have lower death rates than do similar NTD patients; and that the overall selection mechanism varies by race. PMID- 1442777 TI - Simultaneous kidney-pancreas transplantation versus kidney transplantation alone: patient survival, kidney graft survival, and post-transplant hospitalization. AB - This study compared patient survival, kidney graft survival, and post-transplant hospitalization between patients who received simultaneous kidney and pancreas (SKP) transplants and those who received a kidney transplant alone (KTA). A total of 3,168 diabetic end-stage renal disease (ESRD) patients, ages 18-45, who began their first ESRD treatment between 1981 and 1989 and received their first cadaveric kidney transplant between 1986 and 1989 were selected for study; patient and kidney graft survival were followed until 1 March 1990. Twelve percent (380) of these patients received SKP transplants. No statistically significant difference in patient survival was found between SKP and KTA patients (p = 0.86). Kidney graft survival was statistically significantly higher for SKP patients than KTA patients (p = 0.008). Post-transplant hospitalization rates were statistically significantly higher for SKP patients (p < 0.001), indicating potentially higher post-transplant morbidity among this group. PMID- 1442778 TI - How good are the data? USRDS data validation special study. AB - Four national samples, totaling 1,692 cases selected from ESRD patients incident in 1986 and 1987, were analyzed to document the reliability of the USRDS database. For these cases, the reported data in the USRDS database were compared with on-site source documents (medical records, hospital discharge summary records, transplant summaries, and billing records). The results show an overall agreement rate of 90.6 percent for over 50 variables. Agreement rates on the most important fields range from a low of 87.0 percent for point-in-time variables (eg, modality of treatment at the end of the year), to a high of 94.9 percent for dates (eg, date of birth, death, first ESRD service). The study concludes that (1) appropriate definitions and protocols are needed in the assessment of the primary disease causing ESRD, and (2) formal definition of when the patient becomes an ESRD patient needs review. This study points to the strengths and limitations of the USRDS database and indicates areas that need to be addressed to improve current and future data collection efforts. PMID- 1442779 TI - Completeness and reliability of USRDS data: comparisons with the Michigan Kidney Registry. AB - A census of 12,730 Medicare-eligible ESRD patients identified in the USRDS database as living in Michigan or as having received treatment in Michigan between 1977 and 1987 was compared to the 13,424 ESRD patients listed in the Michigan Kidney Registry (MKR) who were alive between 1977 and 1987. Of 7,600 USRDS patients with both residence and ESRD treatment in Michigan, 97.8 percent were also found in the MKR, thus providing evidence that the USRDS is not overstating the size of the ESRD population. Overall, 11.4 percent of the cases in the MKR could not be matched to the USRDS; however, the rate of matching showed a slight upward trend over time. Subsequent analysis shows that after excluding those cases expected not to be captured by the Medicare system, only 5 percent of MKR cases were left unmatched to USRDS cases. Some of these unmatched cases from the MKR were found to have short follow-ups, while others belong to groups not covered by Medicare without being noted as such by the MKR database. A high level of exact agreement on data elements for cases found in both databases was documented for demographic variables, above 90 percent. However, differences were found between the USRDS and the MKR databases on elements related to treatment history. It is likely that a lower precision of the dates associated with treatment episodes and difficulty in recording short term treatment episodes in the USRDS could account for the differences found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442780 TI - Improvements in data quality in the USRDS database: determining treatment modalities. AB - Past USRDS estimates of the prevalent ESRD population have exceeded the counts reported by the HCFA Annual Facility Surveys. One expects the USRDS estimates to be lower because the Facility Surveys include non-Medicare patients generally not in the USRDS database. The methodology for determining the treatment histories of patients has been modified to define lost to follow-up periods as periods of at least one year during which the patient has no dialysis data and does not have a functioning transplant. Patients are not counted as prevalent when they are in such a lost to follow-up period. This change brings the USRDS year end prevalent counts down to about 94 percent of the Facility Survey counts of total dialysis patients and slightly over the Facility Survey counts of Medicare dialysis patients. This change raises prevalent mortality rates by about seven percent over the rates reported in the 1991 USRDS Annual Data Report. We expect to make further refinements in this methodology. PMID- 1442781 TI - USRDS research studies. PMID- 1442782 TI - Use of death certificates in epidemiological studies, including occupational hazards: discordance with clinical and autopsy findings. AB - There has long been evidence of frequent inaccuracy of death certificates, with significant discordance between such designations and clinical and autopsy data. This exists for occupational diseases as well. The use of statistical rates based on death certificates has been seriously questioned despite their utility for total mortality. Programs to supplement death certificate data, particularly in occupational disease studies, may be helpful, and are reviewed. PMID- 1442783 TI - Use of death certificates in epidemiological studies, including occupational hazards: variations in discordance of different asbestos-associated diseases on best evidence ascertainment. AB - There is extensive information on discordance in general between accuracy of medical diagnoses on death certificate categorization of cause of death and available clinical and histopathological data. This is as true for occupational disease as for other conditions. But occupational illnesses bear a special problem. Discordance is not equal across the board--it may vary with each occupationally related disease, and no single formula can be applied. It may be high for angiosarcoma and low for acute hydrogen sulfide poisoning, low for bladder cancer, high for unsuspected methyl mercury poisoning. We have found that for one agent--asbestos--there were different rates of discordance for different asbestos-related diseases (e.g., lung cancer, mesothelioma, asbestosis, kidney cancer) among 4,951 deaths studied prospectively from 1967 to 1986. Caution is therefore required before accepting generalizations concerning (unstudied) discordance in occupational mortality studies, and in their use in risk assessment models. PMID- 1442784 TI - Death certificates in epidemiological studies, including occupational hazards: inaccuracies in occupational categories. AB - We compared death certificates for asbestos-associated diseases (mesothelioma, lung cancer, asbestosis) in two asbestos workers' cohorts. One (insulation workers) had current or recent employment and a strong, continuing union support system which gave them much information about the effects of asbestos exposure. The second cohort, asbestos factory workers, had no such advantage. The factory had closed almost 30 years before, and its workers had dispersed into many areas of the state and nation. Accuracy of medical diagnosis was comparable in the two groups, but occupational listings were not. Three-quarters of the insulators' death certificates told of asbestos work, while virtually none of the factory workers' certificates provided such information, even for deaths of mesothelioma and asbestosis. The data indicate that disease categories, based on medical and pathological diagnoses, at least for asbestos-associated disease, tend to be accurate. Attempts to identify groups at risk by sorting occupational categories can give variable results, good for those with current exposures, much less satisfactory for those with long-past occupational exposures. PMID- 1442785 TI - Influence of age at death on accuracy of death certificate disease diagnosis: findings in 475 consecutive deaths of mesothelioma among asbestos insulation workers and asbestos factory workers. PMID- 1442786 TI - A case-control study of cancer of the nose and paranasal sinuses and occupational exposures. AB - The association between nasal cancer and various occupations was investigated in a case-control study in the provinces of Verona and Vicenza (northeastern Italy) and Siena (central Italy). Cases of malignant epithelial neoplasm of the nasal cavities and paranasal sinuses diagnosed in the years 1982-1987 in the hospitals of Verona, Legnago, Bussolengo, Vicenza, and Siena comprised the study. Controls were patients admitted to the same hospitals as the cases, with any diagnosis except chronic rhino-sinusal disease and nasal bleeding. Age, gender, residency, and date of admission were taken into account by matching. Cases and controls, or their next of kin, were interviewed or required to fill in a mailed questionnaire; the overall response rate was 70%. Altogether, 78 cases and 254 controls provided information on occupational history. Significantly increased risks were associated (in males) with work in the wood industry (odds ratio [O.R.]: 5.8; 90% confidence interval [C.I.]: (2.2-16) and in the leather industry (6.8; 1.9-25). Textile workers, furnacemen, construction workers, and workers with possible exposure to organic dusts showed increased risks even if statistical significance was not reached. PMID- 1442787 TI - Malignant mesothelioma of the pleura in Trieste, Italy. AB - One hundred and seventy malignant pleural mesotheliomas seen at necropsy at the Institute of Pathological Anatomy of the Trieste University during the period 1968-1987 were reviewed. The series included 153 men and 17 women, aged between 33 and 92 years (median 70 years). Lifetime work histories were obtained from the patients' relatives by personal or telephone interviews in 162 cases. A majority of the male subjects had been employed in "naval" work, 99 people having worked in the ship-building industry, 19 in the navy and merchant marine, and 7 in docks. A variety of trades appeared in the remaining histories. Work histories were indicative of occupational exposure to asbestos in 150 cases. A further 5 patients with negative or insufficient data showed asbestos bodies in routine lung sections and 5 women had a history of domestic exposure. A majority of the patients had had their first exposure before 1950. The intervals between first exposure and death ranged from 14 to 71 years (median 48 years). PMID- 1442788 TI - Acute high dose exposure to benzene in shipyard workers. AB - Fifteen degassers were acutely exposed over several days to high concentrations (> 60 ppm) of benzene during removal of residual fuel (degassing) from shipboard fuel tanks. Medical surveillance evaluation mandated by the Occupational Safety and Health Administration's (OSHA) Benzene Standard initially revealed 11 workers (73%) reporting neurotoxic symptoms while degassing. Workers with more than 2 days (16 hours) of acute exposure were significantly more likely to report dizziness and nausea than those with 2 or fewer days of acute exposure. Repeated laboratory analyses performed over a 4-month period after the acute exposure revealed at least one hematologic abnormality consistent with benzene exposure in 9 (60%) of these degassers. One year later, 6 workers (40%) had persistent abnormalities; an additional worker with normal hematologic parameters at the time of our initial evaluation subsequently developed an abnormality consistent with benzene exposure. Numerous large granular lymphocytes were observed on 6 (40%) of the peripheral blood smears. Despite these laboratory findings, there were no significant associations between the presence of hematologic abnormalities and either the number of hours of acute benzene exposure or the duration of employment as a degasser. Volatilization of benzene from the residual fuel was the suspected source of benzene in the headspace of tanks. Confined space exposure to petroleum products may be exposing workers to benzene at levels above the OSHA Short-Term Exposure Limit (STEL). This situation warrants further study. PMID- 1442789 TI - Study of sperm characteristics in persons occupationally exposed to lead. AB - The sperm characteristics of 38 male workers exposed to lead in a battery factory were studied. Sperm analysis was performed after 4 days of sexual abstinence. Parameters analyzed were: volume, sperm count, motility, and morphology. Exposure levels were estimated by measuring the concentration of lead and delta aminolevulinic acid in the serum. Based on blood lead levels, the tested individuals were divided in three groups: A (12), B (11), and C (15). Significant levels of asthenospermia and teratospermia were found in exposed workers when compared with unexposed controls. Long-term exposure to lead may lead to changes in sperm characteristics and function. PMID- 1442790 TI - Epidemiologic evidence of cancer in aluminum reduction plant workers. AB - This paper reviews the epidemiologic evidence of cancer risks among workers in aluminum reduction plants with emphasis on associations with specific work areas and exposures. Studies of workers manufacturing carbon products outside the aluminum industry were also reviewed since the work environment is similar to that encountered in the carbon area of aluminum plants. We obtained 22 reports from references cited in earlier reviews, through compact disc literature search 1980-1990, and from the Nordic Aluminum Industry's Secretariat for Health, Environment and Safety. Six reports were excluded because the material was included in later studies or because a critical evaluation was impossible. This left 16 publications from 11 separate studies. Work in potrooms with Soderberg electrolytic cells was associated with increased risk of bladder cancer, and the increase was correlated to duration of tar exposure. There was a suggestion of increased risk of leukemias and pancreatic cancers in potroom workers, and of kidney and brain cancers without any clear association with specific exposures or work areas. Singular results showed associations between lung cancer risk and tar exposure in Soderberg plants, and between lung cancer and work in prebake or carbon plants, but interpretation was limited by inadequate data on smoking and asbestos exposure, and by problems connected with the choice of reference populations in these studies. PMID- 1442791 TI - Pneumoconiosis research in South Africa with emphasis on developments in the last quarter century. PMID- 1442792 TI - Was the literature "corrupted"? PMID- 1442793 TI - Health and safety education for worker empowerment. AB - This article introduces a special issue of the American Journal of Industrial Medicine dedicated to innovative approaches to worker education in health and safety. Contributors to this issue describe applications of an "empowerment approach" in a wide variety of institutions and settings throughout the United States and Canada. In this article, empowerment education is presented and contrasted with other training methodologies. The article offers suggestions on how to implement this approach discusses evaluation issues, and summarizes the articles contained in this issue. Explored are preliminary outcomes of using this methodology and implications for developing educational programs in the future. PMID- 1442794 TI - Workshops are not enough: making Right-to-Know training lead to workplace change. AB - The underlying intent of Right-to-Know laws and regulations is to improve workplace conditions through worker empowerment. These regulations require employers to educate their employees about the nature and hazards of toxic substances found in the workplace, and methods to reduce exposure. This paper describes a Right-to-Know training program for over 4,000 local government employees which involved workers, their union, and management in the planning, implementation, and evaluation of the program. A combination of quantitative and qualitative evaluation determined the program was successful at individual, group, and structural levels. The evaluation results suggest that Right-to-Know training programs can make an important contribution to improving workplace health and safety when they are a well-integrated component of a comprehensive safety and health program: they use participatory training methods, they are tailored to address specific conditions faced by the participants, and there is active labor-management collaboration. PMID- 1442795 TI - A participatory workplace health and safety training program for ethylene oxide. AB - The Occupational Safety and Health Administration (OSHA) has regulated ethylene oxide (EtO) on the basis of its acute toxicity and its potential carcinogenic and reproductive effects since 1971. OSHA's 1984 EtO standard and its 1988 revisions focused new attention on health and safety training and other preventive measures. An EtO health and safety training program for hospital sterilization workers was developed by the staff of an independent occupational and environmental health clinic. Participatory and empowerment training methods were central to the approach. Also included were hands-on, demonstration, interactive presentation, and other methods. An EtO Health and Safety Training Manual was developed based on the training experiences. This paper presents the challenges, benefits, and limitations of incorporating participatory and empowerment approaches in the design, implementation, and evaluation of EtO health and safety training. PMID- 1442796 TI - Teaching health and safety: problems and possibilities for learner-centered training. AB - The University of Massachusetts at Lowell Work Environment Department, working jointly with four New England coalitions on occupational safety and health (COSH) groups, has developed and is delivering participatory and learner-centered health and safety training for hazardous waste site workers and emergency responders throughout New England. This consortium has created a technical curriculum for hazardous waste workers accessible to the nonspecialist and which, more importantly, draws upon workers' own experience and knowledge as a source of information, education, and experiential resources. In this article, we examine the goals of the consortium, the applicability of the training method, its successes and failures, and the wider implications such pedagogical techniques have for effective and empowering health and safety training. We conclude that such a teaching technique is a successful means of providing technical knowledge and skills in a positive and rewarding atmosphere. We also conclude, however, that the extent to which this form of education is empowering, as is claimed by many of its proponents, is less clear-cut. PMID- 1442797 TI - Problem-solving in the fields: an action-oriented approach to farmworker education about pesticides. AB - This paper describes two educational programs initiated to address the problems of farmworker pesticide poisoning in Nicaragua and in the United States and Puerto Rico. Both programs utilize a participatory and action-oriented educational methodology known as popular education. The methodology is presented using examples to demonstrate its application to the planning, delivery and evaluation of pesticide education programs. Preliminary outcomes of using this methodology are also explored as well as implications for developing future training programs in the field. PMID- 1442798 TI - Hardware to hard hats: training workers for action (from offices to construction sites). AB - A university-based labor education program provides training to unionists, emphasizing the skills needed by workers and their representatives in order to promote their rights to health and safety on the job. The article describes two examples of this training approach. The first example is a training program for video display terminal (VDT) operators which prepares them to take a leadership role in advancing policies to regulate working conditions for VDT users. The second is a program designed to improve the quality of safety, or "tailgate" meetings in the construction industry by promoting an approach that encourages active worker participation in identifying potential hazards and developing solutions. The methodologies used to achieve action-oriented outcomes are described. PMID- 1442799 TI - "Let's Talk Back": a program to empower laundry workers. AB - Laundry workers have traditionally been offered little input into the ergonomic and health and safety aspects of their jobs. The "Let's Talk Back" program was developed in response to worker demands, in order to empower them to effectively address some of these concerns. The program, endorsed by the union and administered by a hospital ergonomist, provided formal educational sessions, physical demand analyses, and a forum in which to communicate concerns and suggestions for improvements. Language and/or literacy barriers required innovative educational approaches. Management's reluctance to allow the program to interfere with production schedules hindered the efficiency of the program, but probably contributed to the sense of empowerment in the workforce. Through active participation in ergonomic assessments as well as the educational program, workers were able to demonstrate to management that changes were needed. PMID- 1442800 TI - Human immunodeficiency virus/acquired immunodeficiency syndrome training from a union perspective. AB - The authors developed a union sponsored 2-day human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) "train the trainer" program for healthcare workers in the San Francisco Bay Area. The program incorporated the "education for action" approach in an effort to respond to the inadequacies in many traditional, institutional trainings. Service Employees International Union (SEIU) and Labor Occupational Health Program (LOHP) conducted the HIV/AIDS "train the trainer" program for approximately 100 healthcare workers in county public hospitals and community health clinics. After completing the program, these workers went back to their healthcare facilities, or community organizations, and led additional classes on HIV/AIDS transmission and prevention for approximately 600 more people. The goal of the program was to empower healthcare workers to: 1) identify the occupational risks associated with exposure to blood and potentially infectious body fluids at the workplace; 2) develop strategies to reduce those risks; 3) discuss their feelings about caring for an HIV/AIDS patient; and, 4) conduct HIV/AIDS workshops at the workplace. PMID- 1442801 TI - Use of participatory training techniques in a right-to-know train-the-trainer course for New Jersey public employees. AB - The New Jersey Department of Health, in conjunction with the Department of Personnel's Human Resources Development Institute, has developed a Right-to-Know Train-the-Trainer course. In this course, various participatory activities have been utilized since the course's inception in December 1989 to train future trainers who train public employees about recognizing, evaluating, and controlling hazardous substances in their facilities. These participatory training techniques have offered a means by which the trainers can encourage workers to become proactive in making their working conditions safer. With the use of various methods of evaluation, course participants learn the content and develop their skills in the use of participatory training techniques. Though evaluations indicate that participants have a favorable impression of the course, the extent to which these participants take the information back to their worksites has not been formally evaluated. PMID- 1442802 TI - Implementing right-to-know legislation for health care workers in Manitoba: a bipartite sectoral train-the-trainer approach. AB - In October 1988, right-to-know legislation was introduced in Canada. This presented a technical and administrative challenge to the health care sector. With over 170 health care facilities in Manitoba to be brought into compliance, some large, some small, some rural, some urban, a cooperative approach was needed. A labor-management steering committee with representatives from a cross section of facilities as well as the various health care unions was formed to design and implement a train-the-trainer program. A small-group, highly participatory modular program was developed with input from all parties, and delivered across the province by trainers selected jointly by labor and management. The program achieved its goal of assisting member facilities to implement the legislation. Follow-up surveys and discussions with health care workers showed improved understanding of labelling requirements, material safety data sheet interpretation, and requirements for hazard control. This first bipartite program empowered the health care workforce to use its newly acquired right-to-know, and has provided the incentive to implement other cooperative safety and health programs. PMID- 1442803 TI - Evaluating a training-for-action job health and safety program. AB - This paper describes an action research evaluation method developed to assess a worker training program which encourages trainees to use knowledge acquired to correct health and safety problems in their workplaces. The project teaches trainees from the same workplace to identify problem areas collectively using a tool called a Risk Chart and then to prioritize problems to work on with the aid of an Action Plan. Follow-up trainee interviews are conducted to determine what impact the training has on trainees. The methodology is presented and preliminary results are discussed, with particular emphasis on the advantages and limitations of this method. PMID- 1442804 TI - Health and safety education for workers with low-literacy or limited-English skills. AB - Low literacy and limited English proficiency have become a growing concern for health and safety educators. With one-fifth of the workforce reading below an eighth-grade level and possibly another tenth having limited English skills, health and safety educators and unions have increasingly become aware that current training programs often surpass the language and literacy abilities of workers being trained. This article describes the dilemmas facing health and safety professionals in incorporating knowledge about language and literacy skill levels. It documents creative strategies and new programs, largely based on participatory and popular education approaches, to provide training that simultaneously matches worker needs and leads to worker empowerment. PMID- 1442805 TI - Coloring the hazards: risk maps research and education to fight health hazards. PMID- 1442806 TI - Waking up the audience: the use of trigger videos in labor education. AB - Use of trigger videos can enhance union education programs by encouraging an active learning process, in which class members can identify with the problems posed in the video, and are motivated to seek a collective action-oriented solution to those situations which exist in their own workplaces. Such an approach empowers workers to develop their own answers in a supportive and mutually reinforcing context. PMID- 1442807 TI - Three participatory exercises on empowerment used in health and safety training of trainers course in Connecticut. AB - In a training-of-trainers course on health and safety sponsored by the Connecticut Council on Occupational Safety and Health and the Division of Worker Education, Workers' Compensation Commission, various participatory exercises have been utilized to train workers who are then expected to train their co-workers. Three of the exercises, including hazard recognition, tackling apathy, and strategies for change are described. PMID- 1442809 TI - ASHP policy on the acceptance of advertising. PMID- 1442808 TI - Some lessons learned from using participatory methods in asbestos worker training. AB - A nonprofit worker training center changed its teaching methods in response to teacher feelings of burnout, student expressions of boredom, and the requests of new staff members. The paper presents one problem-solving case study that was developed. The author discusses some obstacles to using the case study, and her experiences in overcoming those obstacles. PMID- 1442810 TI - AACP house of delegates vote: colleges to move to sole entry-level Pharm.D. PMID- 1442811 TI - Educational program reduces psychoactive drug use in nursing homes. PMID- 1442812 TI - Changes in FDA drug classification and priority review policy. PMID- 1442813 TI - Ensuring employees' skills. PMID- 1442814 TI - Development of i.v. push guidelines. PMID- 1442815 TI - Expanding pharmacy drug information efforts to counter pharmaceutical marketing. PMID- 1442817 TI - Examining motives for opposition to the sole entry-level Pharm.D. degree. PMID- 1442816 TI - Stability of mitomycin for ophthalmic use. PMID- 1442818 TI - Formalizing a pharmacy student teaching program in an Indian Health Service pharmacy. PMID- 1442819 TI - Transition. PMID- 1442820 TI - The future of health care. AB - Future changes in patient care to curb costs and refocus on health versus medical care are discussed, and efforts at the New England Medical Center (NEMC) to measure patient outcomes and reorganize the delivery of care are described. Medical care is not the only determinant of an individual's health; lifestyle choices and the community also play important roles. The rate of increase in the cost of medical care must be contained. The future of health-care reform will be predicated on packages for the administration of care; for any given condition, all of the elements of medical care would be combined so that clinical and functional outcomes are achieved at a given price (episode-of-illness pricing). The success of medical care should be determined on the basis of the patient's ability to function, not on clinical indicators alone. Also, the prices for new generations of drugs should be determined on whether the new drugs improve patients' quality of life. Health-care professionals in hospitals should not be divided according to their specialties; instead, they should compose multidisciplinary teams that can care for patients over time. NEMC is developing a process and structure in which various health-care professionals work together to design health-care plans that cover a full episode of illness. The future of health care will also be influenced by global trends, including international medical-care inflation, standardization of process and outcome measurements, and a shift in emphasis from medicine to health. The health-care industry is in transition as this country searches for the best way to improve the health and functioning of each citizen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442821 TI - Pharmacy practice in 2040. AB - Pharmacy practice 50 years in the future is discussed. The practice of pharmacy in 2040 will be influenced by many trends and issues, such as increasing cultural diversity, the aging population, evolving drug and information technology, rising drug costs, and increasing third-party coverage. Pharmacy may take one of two paths. In the first scenario, institutional and community practice would drift further apart, with community pharmacy becoming more involved with retailing than with health care. In the second scenario, all pharmacists would become a vital component of an integrated, patient-centered system of health care; pharmacists, like physicians, would be salaried professionals, paid for by health-care programs financed through health insurance. The difference between the two scenarios is the degree to which pharmacists actively participate in their creation: The first will happen if pharmacists do not take action; the second will require a considerable amount of work. If pharmacists wish to see an active system of patient-centered pharmaceutical care in 2040, they must begin to create it now, regardless of their practice setting. Pharmacists must work to create a future in which they are an integral part of the health-care system. PMID- 1442822 TI - ASHP and its customers. PMID- 1442823 TI - ASHP and membership commitment. PMID- 1442824 TI - Antibiotic-impregnated cement use in U.S. hospitals. AB - The results of a survey of the use of antibiotic-impregnated bone cement and cement beads in U.S. hospitals are reported. A random sample of hospitals was selected from all hospitals registered with the American Hospital Association. A questionnaire designed to characterize the extent of use of the products and the degree of pharmacy involvement was mailed to the pharmacy directors at 547 hospitals nationwide. The response rate was 61.7% (336 evaluable returns). Ninety hospitals (26.9%) reported using antibiotic-impregnated bone cement or cement beads. Product use was significantly greater in urban hospitals, hospitals larger than 200 beds, teaching hospitals, and hospitals with pharmaceutical services in the operating rooms. Most facilities using the products were community hospitals. Total hip arthroplasty, total knee arthroplasty, and chronic osteomyelitis were the most common indications for use. Systemic antibiotics were also administered in the great majority of hospitals reporting use of the products. The products were generally used in fewer than one procedure per month. Aminoglycosides and various cephalosporins were the antibiotics most commonly used; most have not been adequately studied for this use. Although nearly all the hospital pharmacies purchased antibiotics for these products, none mixed cement and only two premanufactured antibiotic beads. About one fourth of the hospitals surveyed reported using antibiotic-impregnated bone cement and cement beads, although the total number of patients being treated was small. PMID- 1442825 TI - Pharmaceutical services to evacuated U.S. military dependents. AB - Pharmacy operations on Guam during Operation Fiery Vigil are recounted. In June 1991 Mount Pinatubo, a volcano near Clark Air Base in the Philippines, erupted and forced the evacuation of the base's population. Some 20,000 military dependents were transported to Guam. Those evacuees who needed medical attention- some 2500 of them--were escorted to a temporary medical unit located in and around Andersen Air Force Base and consisting of Army, Navy, and Air Force elements. Full-service health care, including 24-hour pharmaceutical services, was available. A central pharmacy and four satellite pharmacies were established. The four-man pharmacy staff went on 12-hour shifts and made frequent trips to all the medical sites. The pharmacy established and maintained drug stocks and supplies and provided drug information, particularly information on therapeutic equivalents. Constant readiness for emergency drug requests was maintained, and the pharmacy was responsible for transporting drugs. The pharmacy also supported the Army Veterinary Service in processing, quarantining, and caring for 1300 pets. Cold, motion sickness, and sunburn preparations and analgesics accounted for more than half the prescriptions filled. Problems included the sheer number of evacuees, language barriers, the difference in formularies used by the pharmacies in the Philippines and Guam, and the physical and psychological stress to which the evacuees were subjected. Teamwork and coordination among the three U.S. military branches made it possible to satisfy the enormous medical and pharmaceutical needs of dependents evacuated from the Philippines after Mount Pinatubo erupted. PMID- 1442826 TI - How to write and publish scientific papers: scribing information for pharmacists. AB - The principles of writing and publishing scientific papers are outlined. Scientific writing can be both professionally and financially rewarding, but many pharmacists hesitate to write for publication. A primary obstacle is not knowing how to begin. Thoughtful planning is the first and most important step. Before writing a word, the writer should identify the main message, audience, target journal, resource materials, type of manuscript, and authorship. The sections of a paper reporting original research include the title, abstract, introduction, methods, results, discussion, conclusion, references, and tables and figures. Some of these elements also appear in review papers and columns. In general, information given in one section should not duplicate information in another. The writer typically drafts the methods section first, followed by the results, the discussion, and the introduction. Along with intellectual responsibility for the paper, an author must assume various ethical responsibilities, such as ensuring that it contains no plagiarism, that all sources of funding have been acknowledged, and that the paper has not been simultaneously submitted to other journals. To enhance the likelihood of publication, the writer should edit the manuscript carefully and follow the target journal's instructions to contributors. Once the writer has submitted a paper, it must pass the muster of editors and, for peer-reviewed journals, outside experts. Several revisions may be requested before final acceptance. Pharmacists who adhere to the established pattern for writing and submitting scientific papers have the best chance of seeing their work in print. PMID- 1442827 TI - FDA requires further trials for antiendotoxin monoclonal antibody products. PMID- 1442828 TI - FDA urges use of recessed-needle or needleless i.v. administration systems. PMID- 1442829 TI - Dealing with conflict. PMID- 1442830 TI - Promoting safe use of vincristine sulfate. PMID- 1442831 TI - Visual compatibility of diltiazem with commonly used injectable drugs during simulated Y-site administration. PMID- 1442832 TI - A pharmacist in the future? PMID- 1442833 TI - ASHP at 50: organizational precepts. PMID- 1442834 TI - Harvey A. K. Whitney Lecture. Of perceived value. AB - Current issues in pharmacy are discussed and recommendations are made to help pharmacy demonstrate its value in health care. There is a need for pharmacy to actively demonstrate and communicate its value in health care. Educational requirements should reflect the values of the profession. In the debate over the entry-level Pharm.D. degree, the profession must not lose sight of the principal goal of elevating the basic competencies of all pharmacists. Graduate-level education will continue to be valuable, but the degrees and programs should be modified to meet current and future needs. Residency training will become increasingly essential. A well-defined corps of pharmacy technicians is needed. The profession should strive to meet the needs of society rather than confining itself to traditional practice definitions. This will involve increased interaction with patients. Also, pharmacy directors must become more creative in allocating existing resources and building arguments for expansion. When patients recognize the value of pharmacy services, they will seek out and demand those services. Pharmacists must get involved in deliberations regarding health-care reform. They have a responsibility to promote preventive medicine and healthy life-styles. They should actively promote the rational use of all medications. Although tremendous progress has been made in advancing the concept of pharmaceutical care, the profession still has work to do in communicating its value to the public. PMID- 1442835 TI - Mirror to ASHP: 1942-1992. AB - Highlights from the history of ASHP are presented on the occasion of the Society's 50th anniversary. Efforts to organize a formal group representing hospital pharmacists, begun in the 1920s, resulted in the formation of a subsection on hospital pharmacy of the American Pharmaceutical Association in 1936. In 1942, ASHP became a distinct organization affiliated with APhA. The body's goals were to establish minimum standards for pharmaceutical services, ensure a supply of well-qualified hospital pharmacists by providing hospital internships, facilitate information exchange, and foster cost-effective use of medicines. The development of practice standards and periodic surveys of hospital pharmaceutical services, educational efforts and accreditation programs, publications, and ASHP's role in the development of principles for hospital formulary systems are described. ASHP's endorsement of unit dose drug distribution and systems for preparation of intravenous admixtures is discussed. The evolution of pharmacists' clinical roles, their increased involvement in drug therapy decisions and the provision of drug information to patients, and the expanded responsibility implicit in the pharmaceutical care concept are traced. Today's ASHP members can build on the work of yesterday's members to provide better pharmaceutical care. PMID- 1442836 TI - Pharmacokinetic consultation program in a pediatric asthma clinic. AB - The effect of a clinical pharmacokinetic consultation program for theophylline on the outcomes of pediatric patients with asthma was studied. The program was established in 1989 at a pediatric asthma clinic. For each patient visit, a clinical pharmacist recorded demographic, clinical, and medication-related information and counseled the parents. When an adjustment in the theophylline dosage was indicated, the pharmacist calculated the appropriate dosage using population pharmacokinetic values. If the pediatrician requested a measurement of the serum theophylline concentration, the time when the blood sample was drawn relative to the last dose was recorded, an average serum theophylline concentration at steady state and individualized pharmacokinetic values were calculated, and the dosage was adjusted accordingly. Patient data were compared among three stages: (1) the month before and the month of entry into the program, (2) months 5 and 6 after entry, and (3) months 11 and 12 after entry. A total of 44 patients were studied during each of stages 1 and 2, and 29 patients were reviewed during stage 3. There was a significant improvement in wheezing from stage 1 to stage 2 and in exercise tolerance and nocturnal coughing from stage 1 to stage 2 and stage 1 to stage 3. Forced expiratory volume in one second improved significantly from stage 1 to stage 2, and there was a significant reduction in the necessity for hospital visits for the treatment of exacerbations of asthma between stages 1 and 2. The daily weight-adjusted dose of theophylline increased significantly after the program began. Asthmatic children taking theophylline had improvements in outcome variables after pharmacokinetic consultation and medication counseling were initiated. PMID- 1442837 TI - Factors affecting pharmacists' selection of rural or urban practice sites in Nebraska. AB - A questionnaire was used to determine why pharmacists in Nebraska chose urban or rural practice sites and to help the University of Nebraska College of Pharmacy encourage students to consider rural practice. Questionnaires were mailed to 1427 Nebraska pharmacists to gather data about their practice, job satisfaction, location of rearing, location of spouse's rearing, and prepharmacy and clerkship training. Usable responses were sorted into those from urban pharmacists (residing in Omaha and Lincoln and their suburban areas) and those from rural pharmacists (all others). Of the 689 usable responses, 315 (45.7%) were from urban pharmacists and 374 (54.3%) were from rural pharmacists. Of the rural pharmacists, 93% [corrected] grew up in communities of fewer than 100,000 people and 60% grew up in communities of fewer than 5,000 people. Respondents cited income potential, desirability of practice site, influence of spouse and family, and quality of children's schools as factors that most influenced their choice of practice site. Based on the survey results, the University of Nebraska College of Pharmacy took actions to recruit students from rural communities and increase students' exposure to rural practice settings. Pharmacists who were reared or trained in rural areas were more likely to practice in rural Nebraska than pharmacists who had only urban experience. PMID- 1442838 TI - Therapeutic interchange of cefazolin with metronidazole for cefoxitin. AB - The effects on patient outcome and drug therapy costs of a therapeutic interchange program using a cefazolin and metronidazole combination in place of cefoxitin were studied. A therapeutic interchange program was initiated in which the pharmacy department automatically replaced orders for cefoxitin with orders for a cefazolin and metronidazole combination. Data were compared for 100 consecutive patients who received cefoxitin before initiation of the program and the first 100 patients who received cefazolin and metronidazole as part of the program. The impact of the program on therapeutic efficacy, adverse effects associated with therapy, and drug therapy costs was assessed. The two patient groups were similar in age, gender, and white blood cell count. The failure rates for treatment or prophylaxis of infection did not significantly differ between the groups. Duration of therapy and incidence of adverse effects did not significantly differ between the groups. The average cost saving was +72 per patient for treatment with cefazolin and metronidazole instead of cefoxitin. A program for therapeutic interchange of cefazolin and metronidazole in place of cefoxitin demonstrated equivalent efficacy and adverse effects, as well as considerable cost savings. PMID- 1442839 TI - Hospital pharmacy directors' perceptions of job stress in staff pharmacists. PMID- 1442840 TI - Guidelines for the safe handling of excreta contaminated by cytotoxic agents. PMID- 1442841 TI - Hospital's refusal to hire HIV-infected pharmacist without restrictions violates Rehabilitation Act. PMID- 1442842 TI - ASHP reports. Empowering ourselves for professional growth. PMID- 1442843 TI - ASHP reports. A powerful, likely story. PMID- 1442844 TI - ASHP reports. Society achieves income milestone. PMID- 1442845 TI - ASHP reports. Building for the future. PMID- 1442846 TI - ASHP statement on the use of medications for unlabeled uses. PMID- 1442847 TI - ASHP statement on the pharmacy and therapeutics committee. PMID- 1442848 TI - ASHP statement on the pharmacist's responsibility for distribution and control of drug products. PMID- 1442849 TI - Management of syphilis in human immunodeficiency virus-infected patients. PMID- 1442850 TI - Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus. AB - OBJECTIVE: To evaluate the effect of ceftriaxone in treating latent syphilis or asymptomatic neurosyphilis in patients infected with the human immunodeficiency virus (HIV). DESIGN: Follow-up study of patients treated at two HIV-based clinics during 16 months from 1989 to 1991. PATIENTS: Patients were those in whom a clinical diagnosis of latent syphilis or asymptomatic neurosyphilis was made, who received all recommended doses of antimicrobial therapy, and who returned for follow-up visits for 6 or more months. RESULTS: Forty-three patients were treated with ceftriaxone, 1 to 2 g daily for 10 to 14 days. Thirteen underwent lumbar puncture before treatment; 7 (58%) had documented neurosyphilis (pleocytosis in 5, elevated protein levels in 6, VDRL reactive in cerebrospinal fluid [CSF] in 7), and 6 had documented latent syphilis (entirely normal CSF). The remaining 30 were said to have presumed latent syphilis. There was no relation between the diagnosis and the selected dosage of ceftriaxone. Response rates were similar in those who had documented neurosyphilis and documented or presumed latent syphilis. Overall, 28 patients (65%) responded to therapy, 5 (12%) were serofast, 9 (21%) had a serologic relapse, and 1 (2%) who experienced progression to symptomatic neurosyphilis was a therapeutic failure. Thirteen patients received benzathine penicillin for presumed latent syphilis; results were similar to those observed after ceftriaxone therapy, with 8 (62%) responders, 1 (8%) serofast, 2 (15%) relapses, and 2 (15%) failures. CD4 cell counts in responders were not different from those who failed to respond. CONCLUSIONS: Even in the absence of neurologic symptoms, half of the HIV-infected persons who have serologic evidence of syphilis may have neurosyphilis. Although ceftriaxone achieves high serum and CSF levels, 10 to 14 days of treatment with this drug were associated with a 23% failure rate in HIV-infected patients who had latent syphilis or asymptomatic neurosyphilis. Three doses of benzathine penicillin did not have a significantly higher relapse rate and may provide appropriate therapy, at least for documented latent syphilis in persons co-infected with HIV. Studies comparing ceftriaxone with 10 to 14 doses of procaine penicillin are needed to determine the most cost effective treatment for asymptomatic neurosyphilis or presumed latent syphilis in this group of patients. PMID- 1442851 TI - Cardiac involvement in patients with myeloproliferative disorders. AB - INTRODUCTION: To evaluate cardiac involvement in myeloproliferative disorders (MPD), two-dimensional and Doppler echocardiographic studies were performed in 30 patients with MPD. PATIENTS AND METHODS: There were 18 women and 12 men, with an age range from 35 to 76 years. Eighteen patients had polycythemia vera (PV), 8 had essential thrombocythemia (ET), and 4 had agnogenic myeloid metaplasia (AMM). RESULTS: Echocardiography revealed valvular lesions in 19 of 30 patients (63%) compared with only 1 of 22 patients (4.5%) in a control group of patients referred for echocardiography to exclude a cardiac source for idiopathic systemic thromboembolism (chi 2 = 13.39, p < 0.001, by chi 2 test with Yates' correction). Valvular lesions were found in 77% of patients with PV, 50% with ET, and 25% with AMM (p = NS). The aortic and mitral valves were the most commonly involved valves, and the most common echocardiographic lesion was leaflet thickening, which was found in 12 patients (40%), followed by vegetations, which were observed in 5 patients (16%). In their past history, 14 of 30 (47%) MPD patients had arterial or venous thrombosis or embolism. Twelve of 19 (63%) patients with valvular lesions had thromboembolism compared with only 2 of 11 (18%) patients without evidence of valvular lesions (chi 2 = 3.99, p < 0.05, by chi 2 test with Yates' correction). Pulmonary hypertension, unrelated to the severity of valvular disease and probably resulting from pulmonary venous occlusion, was found in four patients (13%). CONCLUSIONS: We conclude that the heart is frequently involved in patients with MPD, particularly when their past history is complicated by a thromboembolic event. Some patients have clinically significant valvular disease. Pulmonary hypertension is another relatively common finding in MPD patients. Echocardiography provides information of clinical significance in MPD patients. A larger number of patients is needed to determine whether the presence of valvular lesions is of prognostic significance and may herald future thromboembolic events. PMID- 1442852 TI - Ascending aorta distensibility abnormalities in hypertensive patients and response to nifedipine administration. AB - PURPOSE: The purpose of the present investigation was to study the distensibility of the ascending aorta in patients with arterial hypertension and normal subjects before and after administration of a calcium antagonist, nifedipine. PATIENTS AND METHODS: The distensibility of the ascending aorta was measured before and after nifedipine administration in 22 male hypertensive patients and 12 age-matched male normotensive subjects. Aortic distensibility was calculated as a function of changes in aortic diameter and pulse pressure, using the formula: 2 x (pulsatile change in aortic diameter)/[(diastolic aortic diameter) x (aortic pulse pressure)]. Aortic diameters were measured by echocardiography and aortic pressures were obtained by catheterization of the ascending aorta. RESULTS: In the basal state, the distensibility of the ascending aorta and aortic strain were lower in hypertensive patients than in normotensive subjects (p < 0.001); the lower aortic distensibility, however, was associated with a greater distending pressure. A good inverse correlation (r = -0.81) was found between mean aortic pressure and aortic distensibility. The aortic distensibility was increased after nifedipine administration in both groups; this increase in aortic distensibility, however, was lower in the patients with hypertension compared with normotensive subjects (p < 0.001). CONCLUSIONS: Aortic distensibility is decreased in patients with arterial hypertension. Nifedipine administration increased the distensibility of the ascending aorta both in patients with arterial hypertension and in normotensive subjects. The increase of aortic distensibility after nifedipine administration was lower in hypertensive patients. PMID- 1442853 TI - Risk factors for coronary artery disease in patients with systemic lupus erythematosus. AB - PURPOSE: To estimate the frequency of and examine risk factors for coronary artery disease (CAD) in patients with systemic lupus erythematosus (SLE) in a prospective longitudinal study. PATIENTS AND METHODS: Patients were SLE are enrolled in The Johns Hopkins Lupus Cohort, a prospective study of outcomes in 229 subjects with SLE. CAD was defined as angina, myocardial infarction, or sudden death. Data on CAD risk factors were obtained prospectively every 3 months and were analyzed using univariate and multiple logistic regression. RESULTS: CAD occurred in 19 (8.3%) of 229 patients with SLE and accounted for 3 (30%) of 10 deaths as of December 31, 1990. Compared to subjects without CAD, those with CAD were more likely to have been older at both diagnosis of SLE (37.1 years versus 28.9 years, p = 0.004) and at entry into the cohort (47.1 years versus 34.7 years, p < 0.0001), to have a longer mean duration of SLE (12.3 years versus 8.1 years, p = 0.013) and a longer mean duration of prednisone use (14.3 years versus 7.2 years, p < 0.0001), to have a higher mean serum cholesterol (271.2 mg/dL versus 214.9 mg/dL, p < 0.0001) or a cholesterol level greater than 200 mg/dL (odds ratio [OR] 14.5, 95% confidence intervals [CI] 1.9, 112.1), and to have both a history of hypertension (OR 3.5, 95% CI 1.3, 9.6) and a history of use of antihypertensive medications (OR 5.5, 95% CI 1.8, 17.2). There were no significant associations with other known CAD risk factors such as smoking, diabetes, family history of CAD, race, or sex, or variables related to steroid therapy including the presence of cushingoid features or ever use of corticosteroids. The best multiple logistic regression model for CAD included age at diagnosis, duration of prednisone use, requirement for antihypertensive treatment, maximum cholesterol level, and obesity (using NHANES-II [National Health and Nutrition Examination Survey] definitions). CONCLUSION: Primary and secondary prevention strategies directed at hypertension, hypercholesterolemia, and obesity, as well as other known CAD risk factors, should be routinely employed in the management of patients with SLE. PMID- 1442854 TI - Tuberculous meningitis in patients with and without human immunodeficiency virus infection. AB - OBJECTIVE: To characterize the symptoms, signs, laboratory findings, and outcome of culture-proven meningitis due to Mycobacterium tuberculosis in patients with and without human immunodeficiency virus (HIV) infection. DESIGN: Retrospective chart review. SETTING: Urban public general hospital in the United States. PATIENTS: Fifteen patients with and 16 without HIV infection. MEASUREMENTS: Demographics, symptoms, physical exam findings, serum sodium, complete blood cell count, CD4+ cell count, cerebrospinal fluid findings, imaging data, and in hospital mortality. MAIN RESULTS: Symptoms, signs, chest radiograph appearance, cerebrospinal fluid cell counts and chemistries, and mortality were similar in both groups (p = NS). Median CD4+ cell counts were lower in HIV-infected patients (median 99/mm3, range 7 to 251, versus 384/mm3, range 171 to 724 in those without HIV infection, p = 0.007). Intracerebral mass lesions were more common in the HIV infected group (60% versus 14% in the uninfected group, p = 0.01), although the presence of a mass did not correlate with focal neurologic deficits, altered level of consciousness, or mortality. CONCLUSION: With the exception of an increased incidence of intracerebral mass lesions in HIV-infected individuals, HIV infection appears to have little impact on the findings and in-hospital mortality of tuberculous meningitis. PMID- 1442855 TI - Microalbuminuria in patients with essential hypertension: effects of several antihypertensive drugs. AB - PURPOSE: Microalbuminuria can be present in 10% to 40% of patients with essential hypertension and is associated with an increased incidence of cardiovascular events. The effect of commonly used antihypertensive agents on urinary albumin excretion (UAE) has not been well established. The aim of this study was to evaluate the effects of a converting enzyme inhibitor, a calcium channel blocker, a beta blocker, and a diuretic on UAE and on creatinine clearance in patients with mild to moderate hypertension. PATIENTS AND METHODS: We prospectively measured UAE prior to and 4 and 8 weeks after treatment with enalapril, nitrendipine, atenolol, or a diuretic in 48 patients with essential hypertension and microalbuminuria. RESULTS: All these agents were equally effective in reducing arterial pressure. However, enalapril but not the other agents significantly decreased UAE. CONCLUSION: Eight weeks of therapy with enalapril may reduce UAE in patients with mild to moderate essential hypertension, whereas other agents, such as nitrendipine, atenolol, or diuretics, had no measurable effect on UAE. The clinical and prognostic significance of these observations remains to be established. PMID- 1442856 TI - Imaging of thoracic Wegener's granulomatosis: the computed tomographic appearance. AB - PURPOSE: Computed tomography (CT) can play a major role in the examination of patients with diffuse infiltrative disorders of the lung. CT patterns of thoracic Wegener's granulomatosis were retrospectively evaluated in this study. The CT appearance was compared with imaging obtained by conventional plain roentgenograms. PATIENTS AND METHODS: Fourteen patients with Wegener's granulomatosis seen during the last 5 years are described. Conventional chest roentgenograms and CT scans from these patients are reviewed. RESULTS: The most frequent manifestation found in the lungs of patients with Wegener's granulomatosis was that of rounded opacities with or without cavitation. This was observed in 7 of 14 patients. Relatively unexpected was the frequent occurrence of bronchovascular bundle cuffing with a quite constant and characteristic bronchocentric distribution. This finding was observed in 5 of 14 patients. Vasculitis sign was demonstrated in 2 of 14 patients. Widespread acinar infiltrates, usually confluent, were common and were seen in 5 of 14 of our patients; in 2 of the patients, these infiltrates were due to diffuse pulmonary hemorrhage. Tracheal stenosis was the cause of sudden acute respiratory failure that was observed in one patient. Pleural disease was present in 3 of 14 patients. Hilar and mediastinal lymphadenopathy was observed in one patient. An interstitial pattern was observed in 3 of 14 patients. CONCLUSIONS: We conclude that an extremely wide spectrum of radiologic findings may be observed in this disease. In 14 patients we found 11 different roentgenographic manifestations; moreover, in 8 patients it was possible to describe more than 1 radiologic manifestation at the same time or during the course of the disease. This observation is not surprising, if we consider the wide variability and broad spectrum of pathologic features in pulmonary Wegener's granulomatosis. Because conventional roentgenograms failed in a great number of cases to visualize the exact pattern and the extent of thoracic involvement, we believe that CT is particularly helpful for the assessment of pulmonary involvement in Wegener's granulomatosis. PMID- 1442857 TI - Physician demographics and the risk of medical malpractice. AB - PURPOSE: This study was undertaken to clarify which, if any, physician demographic characteristics are associated with an increased rate of medical malpractice claims. METHODS: We analyzed the malpractice experience of 9,250 physicians insured for at least 2 years from 1977 to 1987 in the state of New Jersey. After adjusting for years at risk, physician claims per year was categorized into low, medium, and high. RESULTS: Male physicians were three times as likely to be in the high-claims group as female physicians, even after adjusting for other demographic variables (relative risk, 3.1; 99% confidence interval, 2.2 to 4.4). Specialty was strongly associated with claims rate, with neurosurgery, orthopedics, and obstetrics/gynecology having 7 to 12 times the number of claims per year as psychiatry, the specialty with the fewest claims. The rate of claims varied with age (p < 0.001) and peaked at approximately age 40. No association was evident between claims rate and a physician's site of training or type of degree. CONCLUSION: Male physicians are three times as likely to be in a high-claims category as female physicians. We suspect that the most likely explanation for this finding is that women interact more effectively with patients. Understanding the reasons for the variation in claim rates between physicians may lead to the development of methods to reduce the overall rate of malpractice claims. PMID- 1442858 TI - Treatment of supraventricular tachycardias with transcatheter delivery of radiofrequency current. AB - Medical therapy for the treatment of supraventricular tachycardias is frequently ineffective and associated with significant side effects, whereas curative surgical approaches have generally been limited by their considerable morbidity and cost. Greater understanding of the mechanisms underlying supraventricular tachycardias has improved our ability to precisely map endocardial areas critical to arrhythmogenesis. Advances in catheter ablation techniques and particularly the use of radiofrequency current to generate thermal energy for ablation have resulted in dramatic success rates for curative catheter ablation. This review examines the physics of radiofrequency current ablation and its application to the treatment of atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia, and arrhythmias associated with the Wolff-Parkinson-White syndrome. The limitations, risks, and cost-effectiveness of this technique relative to medical and surgical approaches are also evaluated. PMID- 1442859 TI - Admission screening by thyroid function tests in an acute general care teaching hospital. AB - To determine the incidence of unrecognized thyroid disease among admissions to a large acute care university teaching hospital, 364 samples taken on consecutive admissions were assayed for thyroid-stimulating hormone (TSH) and free thyroxine index (FTI). Patients with abnormal test results were further evaluated by determination of antimicrosomal and antithyroglobulin antibodies, and charts were reviewed for evidence of prior diagnosis of thyroid disease, especially severe illness, drug treatment that might affect thyroid function tests, and prior diagnosis of thyroid disease. Results of subsequent thyroid function tests performed during the patient's hospitalization were correlated with the admission serum assays, and data on subsequent testing during the following 6 months were also obtained. A total of 3.9% of patients had significantly depressed TSH, and 11.1% of values were significantly elevated. A total of 11.3% of patients had significantly low FTI values, and 1% had significantly elevated values. A total of 7.4% appeared to have the euthyroid sick syndrome, 5.8% appeared to have unrecognized or undertreated primary thyroid failure, 6% had apparent subclinical hypothyroidism, 2% were thyrotoxic, and 2.8% (all women) had suppressed TSH levels for inapparent reasons. Limiting testing to patients over 49 years of age, or to women, would have missed many individuals with abnormal test results. Considering widespread availability of tests, relative costs, and value of the information obtained, it is suggested that the FTI determination would provide an appropriate screening test for patients in a population such as this entering a large, acute care general hospital. PMID- 1442860 TI - Country doctors of Humble Pie. PMID- 1442861 TI - Abdominal pain and hematologic abnormalities in a 71-year-old woman. PMID- 1442862 TI - Concomitant oculoglandular and ulceroglandular fever due to herpes simplex virus type I. AB - Herpes simplex virus is a commonly encountered infectious agent in clinical practice. The syndromes with which it is usually associated are well described and generally easily recognized. This report documents that two uncommon clinical syndromes, ulceroglandular fever and oculoglandular fever, may be caused by this virus. Our patient's case was even more unusual in that both conditions occurred simultaneously. PMID- 1442863 TI - Digital gangrene following chemotherapy for AIDS-related Kaposi's sarcoma. PMID- 1442864 TI - Is measurement of venous oxygen saturation useful in the diagnosis of cyanide poisoning? PMID- 1442866 TI - Less-recognized risks of blood transfusion. PMID- 1442865 TI - Axillary lymphadenopathy in a healthy population and its relationship to antiperspirants. PMID- 1442867 TI - Tumor necrosis factor in pathogenesis of familial Mediterranean fever. PMID- 1442868 TI - Earlobe crease and coronary artery disease: association or coincidence? PMID- 1442869 TI - Case report: acromegaly and Cushing's disease in a patient with synchronous pituitary adenomas. AB - A 40-year-old white woman presented with hirsutism, amenorrhea, generalized fatigue, diffuse weight gain, acral changes, and coarsened facial features. Physical examination revealed mild diastolic hypertension, acromegalic features, hirsutism, and seborrhea. The growth hormone concentration was elevated and did not suppress after glucose administration. Urinary free cortisol excretion was increased and was not suppressed during a 2 mg low-dose dexamethasone suppression test. Magnetic resonance imaging of the sella demonstrated a 1.3 x 1.2 x 0.8 cm pituitary adenoma. Trans-sphenoidal resection was performed, and portions of the resected tumor were analyzed by routine pathologic methods. Histopathologic and immunohistochemical findings indicated discrete growth hormone- and adrenocorticotropic hormone-producing pituitary adenomas. Coexisting acromegaly and Cushing's syndrome due to pituitary neoplasia was previously reported in two patients. However, to the authors' knowledge, this represents the first description of a patient with acromegaly and Cushing's disease resulting from discrete synchronous adenomas of the pituitary gland as defined by modern histopathologic techniques. PMID- 1442870 TI - Case report: factitious hypoglycemia in diabetic patients. AB - Factitious hypoglycemia (FH) in a diabetic patient represents a difficult diagnostic and costly management problem. An adolescent diabetic with FH is reported. A literature search revealed 10 adolescent and 45 adult diabetic patients with FH. Tests currently available for diagnosis are evaluated. The role of psychiatric therapy in relation to overall management and prognosis is stressed. PMID- 1442871 TI - Case report: acute focal bacterial pyelonephritis (lobar nephronia)--presentation as a palpable abdominal mass. AB - Acute lobar nephronia, or focal pyelonephritis, is an uncommon form of renal infection with a distinct computerized tomographic appearance. A patient is presented with lobar nephronia characterized by fever, flank pain, urosepsis, and painful abdominal mass. Differentiating this condition from abscess or other renal mass is important, because the treatment of lobar nephronia is nonsurgical. The infection responds to antibiotic therapy. PMID- 1442872 TI - Hypertension in blacks: socioeconomic stress and sympathetic nervous system activity. AB - Primary hypertension is almost twice as prevalent among American blacks as among whites. Causes of this increased prevalence of hypertension remain elusive. Elevation of sympathetic nervous system activity, in part secondary to increased levels of socioeconomic stress, is hypothesized as playing a role. Increased sympathetic nervous system activity may increase peripheral vascular resistance directly or through increased vascular reactivity. Microneurography allows direct measurement of peripheral sympathetic nervous system activity. Application of this technique will allow comparison of sympathetic nervous system activity in black and white subjects and provide additional insight into the role of the sympathetic nervous system in the development of hypertension in blacks. PMID- 1442873 TI - Diuretics in the therapy of hypertension: current status. AB - Diuretics were the first effective oral agents for treating hypertension. They have proven to be safe and effective. Recently, they have been scrutinized as possibly being responsible for certain side effects that may increase risk for cardiovascular morbidity and mortality. A careful review of the literature suggests this class of agents warrants continued use as first-line therapy of hypertension, especially in certain demographic groups. However, monitoring of potential baleful effects and a general reduction in dosage are appropriate. Furthermore, selection of other (alternative) agents for monotherapy is advised in certain clinical circumstances. PMID- 1442874 TI - A new twist in the brain-gut axis. AB - Gastrointestinal functions are precisely regulated by hormonal and neural negative feedback loops. In addition to the classic hormonal and vago-vagal reflex mechanisms, these studies indicate that there are direct actions of gut hormones on the dorsal vagal complex. The current data demonstrate that pancreatic polypeptide is released into the circulation by vagal-cholinergic dependent mechanisms. It travels to the brainstem in the circulation, transverses the blood-brain barrier through "leaky" regions of this barrier in the area postrema and nucleus of the tractus solitarius and binds to specific receptors in the dorsal vagal complex. By binding to these sites, pancreatic polypeptide can directly inhibit vagal input to the pancreas and other gastrointestinal organs. These observations provide an anatomic basis to explain why pancreatic polypeptide is a more potent inhibitor of the action of central stimulants of pancreatic secretion than it is of the response to peripheral secretagogues. They also establish a novel mechanism by which gut peptides can influence brain function directly. PMID- 1442875 TI - Commingling and complex segregation analysis of fasting plasma glucose in the Lipid Research Clinics family study. AB - Commingling and segregation patterns of fasting plasma glucose (GL) were examined in family data from 5 clinics (Cincinnati, Stanford, Iowa, Minnesota, and Oklahoma) of the Lipid Research Clinics (LRC) family study. In addition to the primary question of whether there was a major gene for GL, a secondary purpose was to investigate the possibility of genetic heterogeneity among the 5 clinics. No statistical support was found for heterogeneity among clinics, either in the commingling of distributions or in the segregation patterns. For the combined clinics sample, both a major effect and a multifactorial component were significant. However, the major effect (accounting for 73% of the variance) was not found to be consistent with a major gene, as the hypothesis of Mendelian transmission was rejected. The most parsimonious model involved equal transmission probabilities, which suggests that the major effect is not transmitted from parents to offspring. Possible sources of this major non Mendelian effect were explored. The multifactorial component accounted for 10% of the variance in GL levels, and no generational differences were noted. Although our study was unable to provide evidence in favor of a major gene effect, it should be noted that a major gene cannot be firmly refuted. For example, a variety of interactions, such as genotype-dependent age effects, could have masked the transmission probabilities. PMID- 1442876 TI - Study of the etiology of deafness in an institutionalized population in Colombia. AB - To identify causative factors we screened 1,715 deaf individuals from 16 schools for the deaf in Colombia. We found evidence of environmental causation in 579 (33.8%) cases, genetic in 608 (35.4%), and in 528 (30.8%) we were unable to identify the etiology. The degree of hearing loss was severe to profound in 1,238 (72.2%), although in 987 (57.5%) of the deaf population studied the hearing impairment was not noticed until 2 to 5 years of age. The frequent association of deafness with other anomalies underscores the importance of a careful clinical and ophthalmologic evaluation in individuals with hearing loss. Our observations also emphasize the need for programs directed towards the prevention of hearing loss, including primary prevention as well as early diagnosis, investigation of possible genetic causes, and rehabilitation of deaf individuals. PMID- 1442877 TI - Utilization and evaluation of living-related donors for patients with adult polycystic kidney disease. AB - Adult onset polycystic kidney disease (ADPKD) causes 10% of all end-stage renal disease in the United States. Use of living-related donors for renal transplants provides significant advantages over cadaver donors. Presymptomatic testing to determine ADPKD status of potential donors by DNA linkage analysis is potentially more accurate than renal ultrasonography for related donors < 30 years old. To determine the utilization of living donor transplants and linkage studies, a survey was mailed to 202 transplant centers in the United Network of Organ Sharing. The 111 respondents reported 5,026 renal transplants done in 1988 of which 390 (7.8%) involved an ADPKD recipient. Only 7% of these 390 transplants utilized a living-related donor compared to the 20% rate reported for all renal transplants. DNA linkage studies were not used by any of the centers performing related donor transplants in 1988 and only 29% reported provision of risk counseling. We conclude that living-related transplants are underutilized for ADPKD recipients due to conservative transplant policies, concern about the inaccuracy of presymptomatic diagnosis, or decreased availability of asymptomatic donors in these families. DNA linkage analysis is also underutilized due to lack of knowledge of its availability and accuracy, concerns about its cost and misconceptions about the accuracy of ultrasonography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1442878 TI - Patterns of acrorenal malformation associations. AB - Limb and urinary tract defects have frequently been reported to occur together as components of a single acrorenal field defect or in many multiple malformation syndromes. However, the concordance of such anomalies has rarely been studied on a population basis or the relationships between specific limb and renal defects defined. This paper documents the patterns of acrorenal associations seen in over 1,500,000 infants born in Hungary in 1975-1984. In all, 1 in 1,800 infants had a limb deficiency and 9% of these (75 cases) had a urinary tract anomaly. Urinary tract anomalies were most commonly seen with radial ray defects, micromelia and amelia. The commonest recognized patterns were VACTERL association and the cloacal exstrophy and caudal regression sequences. Chromosomal and single gene defects also occurred. Numerical taxonomic techniques delineated six main clusters of patients. Important groupings included micromelia with renal agenesis, split hand/foot with hydronephrosis, and radial ray anomalies with VACTERL defects. The radial ray groups differed in the nature of the VACTERL anomalies seen and with respect to laterality, symmetry, and non-VACTERL anomalies. There was a strong association of bilateral limb defects with bilateral renal anomalies and unilateral with unilateral. Ipsilateral defects tended to occur in typical VACTERL cases, while contralateral defects tended to occur with additional non VACTERL midline anomalies. Although renal and limb anomalies are associated, in almost all cases malformations in other systems are also present. The precise nature of the malformation patterns seen appear to reflect differences in the nature and magnitude of the underlying dysmorphogenetic processes as well as the timing of their effects. PMID- 1442879 TI - Exclusion of human proteoglycan link protein (CRTL1) and type II collagen (COL2A1) genes in pseudoachondroplasia. AB - Patients with pseudoachondroplasia have a skeletal dysplasia with marked short stature. The most common cause of this condition is an autosomal dominant mutation, although autosomal recessive inheritance has been reported. Linkage to 2 cartilage-specific candidate genes, type II collagen (COL2A1) and proteoglycan link protein genes (CRTL1), was tested in 9 autosomal dominant families with pseudoachondroplasia. Tight linkage to these candidate genes was excluded with LOD scores for COL2A1 of -2.45 at theta = 0.05 and for CRTL1 of -7.28 at theta = 0.001. Discordant inheritance of the disease phenotype with each of these genes was also observed. Thus, these 2 candidate genes can be excluded as the cause of disease in these families. PMID- 1442880 TI - Cardiovascular abnormalities in the oculo-auriculo-vertebral spectrum (Goldenhar syndrome). AB - We describe the phenotypic characteristics of 25 individuals with oculo-auriculo vertebral spectrum (OAVS) and its variants, seen in Northern Ireland between 1969 1989, with special reference to cardiovascular defects. We report the type and prevalence of cardiovascular findings and also estimate the minimum prevalence rate of OAVS to be 1 in 45,000. PMID- 1442881 TI - Neonatal hemochromatosis: genetic counseling based on retrospective pathologic diagnosis. AB - We report a case of neonatal hemochromatosis in which the genetic counseling was initiated by, and based on, retrospective pathologic diagnosis. Perinatal or neonatal hemochromatosis is beginning to be recognized as a distinct clinical entity and one of the most common causes of perinatal cirrhosis. The exact mechanism of liver damage and the relationship to adult type hemochromatosis have not been fully clarified. The pattern of fibrosis in the liver plus the abundant iron deposition in the liver and other organs separate this entity pathologically from other causes of neonatal liver failure. We report on a case of neonatal hemochromatosis that was diagnosed on retrospective autopsy review of an infant with supposed hereditary tyrosinemia, when the family presented for genetic counseling. This case emphasizes to the genetic counselor and pathologist the need to consider the diagnosis prenatally, after birth, or at death, as failure to do so would result in the inability to identify families at genetic risk for neonatal hemochromatosis or in mislabeling a family with another inborn error. PMID- 1442882 TI - Boy with a chromosome del (3)(q12q23) and blepharophimosis syndrome. AB - We report on a 6-year-old boy with de novo 46,XY,del(3)(q12q23) and bilateral blepharophimosis, ptosis, epicanthus inversus, in addition to multiple other anomalies. Since 4 previously reported cases of interstitial deletion of 3q involving 3q23 band are clinically similar, we propose this blepharophimosis sequence due to 3q23 deletion as a further "contiguous gene syndrome." PMID- 1442883 TI - Trisomy 22 with congenital diaphragmatic hernia and absence of corpus callosum in a liveborn premature infant. AB - We report on a liveborn premature male with trisomy 22 who had multiple congenital anomalies, including congenital diaphragmatic hernia and absence of corpus callosum. He died of pulmonary hypoplasia associated with diaphragmatic hernia within 12 hours of age. Chromosome analysis by multiple banding techniques based on lymphocyte culture confirmed that he had trisomy 22. This may be the first report of congenital diaphragmatic hernia and isolated absence of corpus callosum associated with trisomy 22. PMID- 1442884 TI - Comparison of phenylketonuric and nonphenylketonuric sibs from untreated pregnancies in a mother with phenylketonuria. AB - Two children, one with phenylketonuria (PKU) and the other nonphenylketonuric, from untreated pregnancies in a mother with PKU provided the opportunity to compare the degree of damage from maternal PKU between these genotypically different fetuses. Both the phenylketonuric offspring and her nonphenylketonuric sib were microcephalic at birth and had congenital anomalies, esophageal atresia in the former and congenital dislocation of the hip in the latter. However, the phenylketonuric child also had intrauterine growth retardation while the nonphenylketonuric sib had normal weight and length at birth. Both children are mentally retarded with an IQ below 50 in the phenylketonuric child despite early dietary treatment for PKU and an IQ of 54 in the nonphenylketonuric sib. Both children also have hypoplasia of the corpus callosum and enlarged cerebral ventricles. This experience and review of the literature indicates that the residual liver phenylalanine hydroxylase activity of a nonphenylketonuric fetus offers little or no protection from damage in untreated maternal PKU. Consequently, the outcome in maternal PKU is likely to depend on control of the maternal biochemical abnormalities in the mother regardless of whether the fetus has or does not have PKU. PMID- 1442885 TI - Golgi-Kopsch silver study of the brain of a patient with untreated phenylketonuria, seizures, and cortical blindness. AB - This report describes the morphological changes observed in the brain of an untreated 27-year-old man with phenylketonuria, cortical blindness, and seizures. Golgi-Kopsch silver, cresyl violet, and hematoxylin and eosin stains were used to study cell structure and organization of the cerebellum, the lateral geniculate nuclei, the visual cortex, frontal cortex, and hippocampus. Extensive neuronal losses occurred in the right lateral geniculate nucleus (LGN), the visual cortex, and hippocampus. The left LGN, cerebellum, and frontal cortex retained neuronal components; there was a reduction in the number of dendritic processes on the Purkinje cells of the PKU subject. The loss of neurons in the LGN and occipital cortex is related to the blindness and the neuronal loss in the hippocampus is related to seizure activity. PMID- 1442886 TI - Molecular detection of a 4p deletion using PCR-based polymorphisms: a technique for the rapid detection of the Wolf-Hirschhorn syndrome. AB - Wolf-Hirschhorn syndrome (WHS) results from a deletion of part of chromosome 4p. The region of 4p consistently deleted in WHS is near the tip of 4p. Two loci in this region D4S95 and D4S125 are associated with highly informative VNTR polymorphisms and were recently converted to allow PCR-based screening. PCR analysis was used successfully to identify a small de novo deletion of 4p in a patient suspected of having WHS. This procedure allows a rapid and accurate confirmation of 4p deletions in cases where cytogenetics alone cannot provide a clear answer. PMID- 1442887 TI - Charcot-Marie-Tooth neuropathy type 1A mutation: apparent crossovers with D17S122 are due to a duplication. AB - A locus for the slow conducting form of Charcot-Marie-Tooth neuropathy (CMT1A) was localised to the proximal short arm of chromosome 17, in band p11.2, distal to D17S58. Linkage studies of CMT1A in 3 large Australian families with the marker loci D17S58, D17S71, and D17S57 suggested the order, pter-CMT1A-D17S71 D17S58-centromere-D17S57. However, the estimate of the recombination fraction between CMT1A and D17S122, also assigned to p11.2, was incompatible with known map distances. The impasse was resolved when the D17S122 genotypes were revised to take into account a dosage effect due to a duplication. After correction of the genotypes, the maximum lod score between CMT1A and D17S122 increased from 0.53 at a recombination fraction of 0.3 to 34.28 at zero recombination. This result emphasizes that genotypes for markers in the p12-p11.2 region should be examined very carefully as ignoring the duplication changes the linkage results dramatically. The fact that no crossovers were found between CMT1A and D17S122 suggests that the duplication may cause the disease phenotype. PMID- 1442888 TI - New syndrome involving the visual, auditory, respiratory, gastrointestinal, and renal systems. AB - A previously undescribed fatal multisystem syndrome involving the eyes, ears, lungs, intestines, and kidneys occurred in sibs. They both presented during early childhood with cataracts, otitis media, intestinal malabsorption, chronic respiratory infection, and failure to thrive. Later, they developed recurrent pneumonia (one was shown to have immotile bronchial cilia) and progressive azotemia leading to end-stage renal disease (ESRD) by late childhood. Both died of overwhelming infection (sepsis, meningitis). An autosomal recessive mode of inheritance is proposed since the normal parents were distant cousins, and 4 other sibs were normal. PMID- 1442889 TI - Biochemical characterization of a pedigree with mitochondrially inherited deafness. AB - A large kindred with a predicted 2-locus inheritance of sensorineural deafness, caused by the combination of a mitochondrial and an autosomal recessive mutation, was examined at the biochemical level. Because of the mitochondrial inheritance of this disease, we looked for defects in the oxidative phosphorylation Complexes I, III, IV, and V, the 4 enzymes that include all of the 13 mitochondrially encoded polypeptides. Biosynthetic labelling of lymphoblastoid cells from deaf patients, unaffected siblings, and an unrelated control showed no difference in size, abundance, rate of synthesis, or chloramphenicol-sensitivity of the mitochondrially encoded subunits. Since overall mitochondrial protein synthesis appears normal, these results suggest that the mitochondrial mutation is unlikely to be in a tRNA or rRNA gene. No change in enzymatic levels was seen in lymphoblastoid mitochondria of the deaf patients, compared to unaffected sibs and controls, for Complexes I and IV. Both affected and unaffected family members showed an increase in Complex III activity compared to controls, which may reflect the mitochondrial DNA shared by maternal relatives, or be due to other genetic differences. Complex V activity was increased in deaf individuals compared to their unaffected sibs. Since the family members share the presumptive mitochondrial mutation, differences between deaf and unaffected individuals likely reflect the nuclear background and suggest that the autosomal recessive mutation may be related to the increase in Complex V activity. These biochemical studies provide a guide for sequence analysis of the patients' mitochondrial DNA and for linkage studies in this kindred. PMID- 1442890 TI - Usefulness of a CACA repeat polymorphism in genotype assignments in Duchenne/Becker muscular dystrophy. AB - RFLP analysis in Duchenne/Becker muscular dystrophy (D/BMD) has been limited by the lack of informative marker loci at the 3' end of the dystrophin gene. Recently a CACA repeat polymorphism was described in the 3' untranslated end of the dystrophin gene which we have found helpful in genotype assignments of D/BMD families when an RFLP approach is required. The CACA repeat marker has 2 common alleles (1 and 2) that are easily visualized by a nonradioactive PCR method followed by polyacrylamide gel electrophoresis. We present 2 families which demonstrate the use of this polymorphism. Since 35-50% of females are heterozygous, this locus is a useful marker in RFLP analysis of D/BMD families. PMID- 1442891 TI - Confirmation of a cryptic unbalanced translocation using whole chromosome fluorescence in situ hybridization. AB - We report on a 7-year-old boy with minor anomalies, growth retardation, and developmental delay with an initial 46,XY,der(18)t(18;?)(q23;?) chromosome constitution. To determine the origin of the additional chromosome segment, several candidate regions were identified including 4q and 18q. Clinical comparison showed more similarities to individuals with partial dup(4q) than to those with a dup(18q). Whole chromosome fluorescence in situ hybridization (FISH) was used to demonstrate the correct origin of the translocated region, clarifying the karyotype as 46,XY,der(18)t(4;18)(q28.2;q22.2), thus generating information of clinical importance. This illustrates the use of whole chromosome FISH to identify chromosome regions that cannot be determined conclusively using standard cytogenetic banding techniques. PMID- 1442892 TI - Update on a family with hand-foot-genital syndrome: hypospadias and urinary tract abnormalities in two boys from the fourth generation. AB - We describe a fourth generation of involvement with hand-foot-genital syndrome. The first 3 generations of this family, which included 5 affected females and no affected males, were reported previously by Verp et al. [1983]. In the fourth generation, 2 affected males are identified. To our knowledge, the findings of bilateral vesicoureteral reflux in one boy and bilateral ureteropelvic junction obstruction in his cousin represent the first reports of urinary tract abnormalities in males with this syndrome. PMID- 1442893 TI - Familial syndrome of endocrine and neuroectodermal abnormalities. AB - We report on a previously undescribed combination of endocrine and neuroectodermal abnormalities in four sibs from Burma. These abnormalities include low growth hormone levels in response to provocative stimuli, delayed puberty associated with prepubertal levels of gonadotropins in the males and pubertal levels of gonadotropins in the females, type II diabetes mellitus with elevated insulin levels, mild mental retardation, sensori-neural deafness, and alopecia without pili torti. They also had a characteristic facial appearance and fleshy hands and feet. This family appears to have a previously undescribed combination of endocrine and neuroectodermal abnormalities. PMID- 1442894 TI - Hepatoerythropoietic porphyria in a woman with short stature and deformed hands. AB - A 23-year-old woman from Honduras was diagnosed to have hepatoerythropoietic porphyria. She had photosensitive skin of early onset, hypertrichosis, and severe scleroderma-like lesions of the hands. Erythrocyte uroporphyrinogen decarboxylase activity was reduced to about 10% of the normal activity. PMID- 1442895 TI - Smallest terminal deletion of the long arm of chromosome 2 in a mildly affected boy. AB - We describe a male twin with the smallest terminal deletion of chromosome 2q [46,XY,del(2)(q37.2)] reported to date. His deletion was confirmed by a fluorescence in situ hybridization study using a probe from the deleted region. Only 3 other cases with larger deletions including 2q37.2-->qter have been reported. Clinical manifestations our patient has in common with them include frontal bossing, long eyelashes, micrognathia, infantile hypotonia and developmental delay. His twin brother is physically and developmentally normal and chromosomes of the parents were normal. The mildness of the phenotype in this patient supports less stringent criteria for cytogenetic study of developmentally impaired individuals. PMID- 1442896 TI - Clinico-pathological conference: a preterm infant with multiple congenital anomalies. AB - A preterm female infant (28 weeks; 880 g) presented with bilateral ectrodactyly of the feet, small cleft palate, esophageal atresia and T-E fistula, multivalvular dysplasia and VSD, thrombocytopenia, and other minor anomalies. Cytogenetic analysis showed trisomy 18. PMID- 1442897 TI - Parental sex effect in spina bifida: a role for genomic imprinting? AB - Fifty families (491 individuals in 137 sibships) with more than one living case of isolated, nonsyndromic spina bifida (SB) were analyzed genetically. There were twice as many gene-carrier females (56) as gene-carrier males (28) (P < 0.005). This was not an artifact of ascertainment bias because the sex ratio of gene carriers was the same whether the pedigree was obtained through the proband's father or mother. Also, this effect was not observed in other disorders analyzed by the same method. Neither was the effect due to differential fertility because the number and sex of affected and unaffected children per gene-carrier parent were not different for male or female gene-carrier parents. There was no evidence that the missing male gene-carriers were lost by selective spontaneous abortion. There was no deficit of male-to-male or male-to-female transmission, excluding simple X-linked or simple mitochondrial inheritance. If genomic imprinting plays a role in the unequal female and male carrier frequencies in SB, penetrance should differ with parental sex. Penetrance was higher for offspring of female parents than of male parents, but the difference was not statistically significant. In addition, both male and female gene-carriers were frequently found in the same pedigree. Thus, the present data suggest a possible role for imprinting in SB. PMID- 1442898 TI - Phenotypic evidence for a common pathogenesis in X-linked deafness pedigrees and in Xq13-q21 deletion related deafness. AB - A structural cochlear abnormality has been observed by high resolution CT scanning in some families where X-linked deafness is segregating. We now present evidence that the same abnormality is present in a deaf patient who has a deletion within Xq21. This observation provides phenotypic evidence that the genotypic basis of deafness is the same in both patient groups. It is also likely that the perilymphatic fluid "gusher" abnormality may be common to both. PMID- 1442899 TI - Craniofacial dysostosis, hypertrichosis, genital hypoplasia, ocular, dental, and digital defects: confirmation of the Gorlin-Chaudhry-Moss syndrome. AB - We report clinical, orofacial and radiological manifestations in a 4-year-old girl and a 33-year-old female with the Gorlin-Chaudhry-Moss (GCM) syndrome. Typical findings in the GCM syndrome are short stature, stocky body build, midface hypoplasia, small eyes, downslanting palpebral fissures, conductive hearing loss, highly arched and narrow palate, malocclusion, abnormally shaped teeth, oligodontia, microdontia, low scalp hairline, hypertrichosis of scalp, face, trunk and limbs and genital hypoplasia. Radiological features include premature synostosis of the coronal suture, brachycephaly, and maxillary under development. Hypoplasia of the distal phalanges of fingers and toes (also present in the 2 original cases) represents a further manifestation of the GCM syndrome. PMID- 1442900 TI - Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells. AB - Five young patients with Niemann-Pick disease type B were treated with repeated implantations of amniotic epithelial cells, as a source of exogenous sphingomyelinase. This treatment abolished the recurrent infections, mainly of the respiratory tract, and led to other improvements of the general conditions of the patients. In particular, we noticed a disappearance of vomiting, a recovery from muscular hypotrophy, and significantly reduced pulmonary distress. In four subjects, who were in a prepuberal state, there was a puberal spurt with a concomitant burst of growth. In two cases, characterized by a greater than normal content of sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Finally, sphingomyelinase activity of peripheral leukocytes, when assayed 0.5 to 4 months after some of the implantations, showed a rise to heterozygous values in 30-40% of the assays. PMID- 1442901 TI - Prader-Willi syndrome in a brother and sister without cytogenetic or detectable molecular genetic abnormality at chromosome 15q11q13. AB - We report on a 12-year-old boy and his 7-year-old sister with the Prader-Willi syndrome. They both had severe initial hypotonia with feeding problems and later developed an increasing appetite. Both sibs have almond-shaped eyes, triangular mouth, hypogonadism, retarded growth, and mental retardation. An older brother suffered from severe hypotonia and died at 7 days of age. The children have normal chromosomes by high-resolution technique and have inherited the same chromosomes 15 short arm polymorphisms from their parents. The family was informative for one of four DNA markers specific for the 15q11q13 region. No deletion was found using this marker. The parents were healthy and unrelated. Autosomal recessive inheritance or a paternally inherited submicroscopic deletion are possible explanations for the sib occurrence in this family. PMID- 1442902 TI - Cartilage-hair-hypoplasia and Hodgkin disease. PMID- 1442903 TI - Pentalogy of Cantrell, ectopia cordis, and frontonasal dysplasia. PMID- 1442904 TI - Waardenburg syndrome and meningocele. PMID- 1442905 TI - Continuous combined conjugated equine estrogen-progestogen therapy: effects of medroxyprogesterone acetate and norethindrone acetate on bleeding patterns and endometrial histologic diagnosis. AB - OBJECTIVES: This study was designed to assess the incidence of amenorrhea with continuous combined therapy by using two different progestogens and to determine whether early bleeding predicts subsequent bleeding and endometrial response. STUDY DESIGN: Seventy-nine postmenopausal women on sequential estrogen progestogen treatment were switched to continuous combined estrogen-progestogen therapy comprising conjugated equine estrogens 0.625 mg daily with either norethindrone acetate 0.35 mg twice daily or medroxyprogesterone acetate 2.5 mg twice daily added continuously for 78 weeks. All bleeding was recorded, and endometrial biopsies were performed at 26 and 78 weeks. RESULTS: Only one third of the women who starting the study had amenorrhea by week 78, but 46 (62%) of these women had withdrawn, mainly because of chronic irregular bleeding. Endometrial atrophy was observed in the majority of biopsy specimens. The two progestogens had similar effects. Bleeding patterns were useful predictors of subsequent bleeding, but not of endometrial response. CONCLUSIONS: Persistent irregular bleeding is common with continuous combined estrogen-progestogen therapy. Women with persistent early bleeding should probably revert to sequential treatment. Regular endometrial sampling is advised. PMID- 1442906 TI - Presacral neurectomy for the treatment of pelvic pain associated with endometriosis: a controlled study. AB - OBJECTIVE: Our objective was to evaluate the efficacy of presacral neurectomy combined with conservative surgery for the treatment of pelvic pain associated with endometriosis. STUDY DESIGN: In a randomized, controlled study performed in a tertiary institution 71 patients with moderate or severe endometriosis and midline dysmenorrhea were randomly assigned to conservative surgery alone (n = 36) or conservative surgery and presacral neurectomy (n = 35). Main outcome measures were relief of dysmenorrhea, pelvic pain, and deep dyspareunia after surgery according to a multidimensional and an analog pain scale. RESULTS: Presacral neurectomy markedly reduced the midline component of menstrual pain, but no statistically significant differences were observed between the two groups in the frequency and severity of dysmenorrhea, pelvic pain, and dyspareunia in the long-term follow-up. After presacral neurectomy, constipation developed or worsened in 13 patients and urinary urgency occurred in three and a painless first stage of labor in two. CONCLUSION: Presacral neurectomy should be combined with conservative surgery for endometriosis only in selected cases. PMID- 1442907 TI - Cold therapy in the management of postoperative cesarean section pain. AB - Sixty-two patients were randomized to receive either localized cold therapy to the cesarean section incision or routine postoperative care. Evaluation of the amount of analgesia requested, infection rate, and length of hospital stay did not show a significant difference between the two groups. There is no objective evidence to show that the use of cold therapy in postoperative cesarean section pain relief is beneficial. PMID- 1442908 TI - The clinical diagnosis of asphyxia responsible for brain damage in the human fetus. AB - OBJECTIVE: Our objective was to review the clinical findings in infants who died in the perinatal period with brain damage attributable to asphyxia. STUDY DESIGN: The neuropathologic findings in 208 perinatal deaths have been reviewed. Thirty cases (22 fetal, eight newborn) had evidence of white matter or neuronal necrosis due to asphyxia. The clinical course of the pregnancy in 22 cases with brain damage attributable to fetal asphyxia were examined. RESULTS: The diagnosis of asphyxia was confounded by several factors: (1) asphyxia may occur at any time in the last half of pregnancy, (2) 50% of the antepartum asphyxia occurred when the pregnancy had no risk factors, (3) periodic fetal assessment in the complicated preterm pregnancies failed to identify the asphyxial episodes in the remaining cases of antepartum asphyxia, and (4) indicators of fetal asphyxia in the cases of intrapartum fetal asphyxia were obtained after the central nervous system injury had occurred. CONCLUSION: These findings highlight the difficulty in the diagnosis of fetal asphyxia at a stage that could permit intervention to prevent brain damage. PMID- 1442909 TI - Perihepatic adhesions: not necessarily pathognomonic of pelvic infection. AB - Perihepatic adhesions are often considered to be associated with pelvic inflammatory disease and subsequent infertility. Seventeen patients out of 100 undergoing elective laparoscopic sterilization had evidence of perihepatic adhesions. Four of the 17 showed evidence of old pelvic inflammatory disease, but only two gave a history of sexually transmitted disease. All patients had a negative gonorrhea culture and 50 also had a negative chlamydia culture before the procedure. These data suggest that perihepatic adhesions may be observed in otherwise normal fertile women, and its presence does not necessarily imply pelvic inflammatory disease or poor fertility. PMID- 1442910 TI - Prophylactic amnioinfusion improves outcome of pregnancy complicated by thick meconium and oligohydramnios. AB - OBJECTIVE: The null hypothesis is that the use of intrapartum amnioinfusion in labors complicated by the presence of thick meconium and oligohydramnios will not decrease the incidence of fetal distress, cesarean delivery, meconium aspiration, or meconium aspiration syndrome. STUDY DESIGN: One hundred seventy term and postterm patients with thick meconium and oligohydramnios were randomly chosen to receive amnioinfusion or standard obstetric care without amnioinfusion. The frequency of fetal distress, cesarean section, meconium aspiration, and meconium aspiration syndrome were subject to chi 2 analysis, Student's t test, or Fisher's exact test. RESULTS: The rate of fetal distress was significantly reduced in the amnioinfusion group compared with controls (three of 85 vs 19 of 85, relative risk 0.15, 95% confidence interval 0.06 to 0.42). The rate of cesarean section for fetal distress was significantly reduced in the amnioinfusion group (two of 85 vs 17 of 85, relative risk 0.118, confidence interval 0.03 to 0.49). The rates of meconium aspiration (four of 85 vs 33 of 85, relative risk 0.12, confidence interval 0.0449 to 0.327) and meconium aspiration syndrome (0 of 85 vs five of 85, relative risk 0.09, confidence interval 0.009 to 0.872) were significantly reduced by amnioinfusion. CONCLUSIONS: Amnioinfusion improves the outcome in pregnancies complicated by thick meconium and oligohydramnios. PMID- 1442911 TI - Spontaneous ovarian hyperstimulation syndrome concomitant with spontaneous pregnancy in a woman with polycystic ovary disease. AB - Ovarian hyperstimulation syndrome has been described after treatment with exogenous gonadotropins, clomiphene citrate, and gonadotropin-releasing hormone. Spontaneous ovarian hyperstimulation syndrome has not been described before, except in association with hypothyroidism. We report on a case associated with spontaneous pregnancy, occurring in a woman with polycystic ovary disease. PMID- 1442912 TI - Screening for Down syndrome with the femur length/biparietal diameter ratio: a new twist of the data. AB - OBJECTIVE: The purpose of this study was to determine the value of discordant morphometric measurements as identifiers of Down syndrome by evaluating the relationship of biparietal diameter, femur length, biparietal diameter/femur length ratio, and cephalic index between a group of fetuses with trisomy 21 and a control population. STUDY DESIGN: Biometric measurements from 48 fetuses with trisomy were reviewed and compared with 107 normal fetuses of similar gestational age. Data were analyzed in 2-week gestational age intervals to determine the effect of gestational age on ultrasonographic detection of Down syndrome. Outcome measures were subject to least-squares linear regression and the t test for analysis. RESULTS: A positive relationship between abnormal morphometric measurements and fetuses with Down syndrome was detected but only during specific weeks of pregnancy. CONCLUSION: Although it appears that biometric measurements may be useful for Down syndrome, further study is needed before its widespread introduction into clinical practice. PMID- 1442913 TI - Rupture of uterine scar with extensive maternal bladder laceration after cocaine abuse. AB - A relationship between cocaine use and extensive rupture of a uterine scar has not been reported. We report such a case with extensive laceration of the maternal urinary bladder occurring after ingestion of cocaine. PMID- 1442914 TI - Comparison of the efficacy of different local anesthetics and techniques of local anesthesia in therapeutic abortions. AB - OBJECTIVES: The objectives of this study were to determine whether carbonated or plain lidocaine provides better pain control during abortions and to determine whether deep injections of lidocaine provide better pain control than regular injections of lidocaine. STUDY DESIGN: Phase 1 was a prospective, randomized, double-blind trial comparing 10 cm3 of 2% carbonated lidocaine with plain lidocaine. In phase 2 the plain lidocaine group in phase 1 was compared prospectively with the next group of patients, in whom a new technique of deep injection was used. A pain scale was administered by the counselor after dilatation and at the end of the procedure. RESULTS: The improvement in pain scores with carbonated lidocaine was 8%. The improvement with the deep injection technique was 25%. CONCLUSION: The improvement in pain scores with deep injection was clinically significant and is recommended. PMID- 1442915 TI - Simultaneous ovarian and intrauterine pregnancy: case report. AB - The simultaneous presence of an ovarian and a normal intrauterine pregnancy is a very rare condition. We report such a case seen as an ovarian cyst during gestation. It was immediately and successfully treated, thus allowing for the normal physiologic continuation of the gestation. PMID- 1442916 TI - Antibodies to Chlamydia trachomatis in sera of women with recurrent spontaneous abortions. AB - OBJECTIVE: The relationship between high-titer immunoglobulin G antibodies to Chlamydia trachomatis and recurrent spontaneous abortions was evaluated. STUDY DESIGN: Sera from the female partners of 258 couples with unexplained infertility, no history of chlamydial infection, and negative cervical cultures were diluted 1:128 and tested for immunoglobulin G antibodies to Chlamydia trachomatis. A subset of patients was also tested for antibodies to cytomegalovirus, cardiolipin, nuclear antigens, lactoferrin, and spermatozoa. RESULTS: Seven (41%) of 17 women with three abortions and 6 (60%) of 10 women with four abortions had chlamydial antibodies as opposed to 20 (13.5%) of 148 with no abortions, 6 (12.8%) of 47 with one abortion, and 4 (12.1%) of 33 with two abortions (p < 0.01). The incidence of > or = 3 spontaneous abortions was 31.8% among women with high-titer chlamydial antibodies and 7.5% among women who had seronegative results (p < 0.001). There was no relation between any of the other antibodies and > or = 3 abortions or antibodies to Chlamydia trachomatis. CONCLUSION: High-titer immunoglobulin G antibody to Chlamydia trachomatis was associated with recurrent spontaneous abortions. The mechanism may involve reactivation of a latent chlamydial infection, endometrial damage from a past chlamydial infection, or an immune response to an epitope shared by a chlamydial and a fetal antigen. PMID- 1442917 TI - Randomized, double-blind study of cefotetan and cefoxitin in post-cesarean section endometritis. AB - OBJECTIVE: The hypothesis of the study is that cefotetan and cefoxitin will be equally efficacious and safe in the treatment of post-cesarean section endometritis. STUDY DESIGN: In a double-blind, randomized manner 140 patients with post-cesarean section endometritis were treated with cefotetan, 2 gm intravenously every 12 hours, or cefoxitin, 2 gm intravenously every 6 hours. They were followed prospectively for clinical response and side effects. Cure rates between the two groups were compared with the chi 2 test. RESULTS: The cure rates were 83% for cefotetan and 79% for cefoxitin (p = 0.56). No patient required a change in therapy due to adverse effects, and no abnormal bleeding occurred. CONCLUSION: In this study cefotetan and cefoxitin appeared equally effective in treating endometritis with no difference in side effects or complications. PMID- 1442918 TI - Interactions between intrauterine contraceptive device use and breast-feeding status at time of intrauterine contraceptive device insertion: analysis of TCu 380A acceptors in developing countries. AB - OBJECTIVE: This paper is a reassessment of earlier findings from a preliminary analysis of data from a multicenter international trial regimen on breast-feeding and non-breast-feeding women in which events related to insertion, expulsion, and removal of the TCu-380A intrauterine contraceptive device (ParaGard 380) were investigated. STUDY DESIGN: Performance of the TCu-380A through 12 months after insertion was compared with life-table rate analysis, chi 2, Fisher exact test, or Student's t test. Variables were events reported during intrauterine contraceptive device insertion and events throughout the 12 months of study participation by breast-feeding status. RESULTS: Breast-feeding among intrauterine contraceptive device users was associated with fewer insertion related complaints and lower removal rates for bleeding and pain. No uterine perforations were reported throughout the study. CONCLUSION: Differences in the performance of the TCu-380A intrauterine contraceptive device suggest physiologic effects associated with lactational amenorrhea. The TCu-380A intrauterine contraceptive device is a viable option for women breast-feeding at the time of intrauterine contraceptive device insertion. PMID- 1442919 TI - Enhanced follicle regulatory protein levels accompany reinitiation of ovulatory function after parturition. AB - OBJECTIVES: We examined the changes in follicle regulatory protein, estrone-3 glucuronide, pregnanediol-3-glucuronide, and luteinizing hormone levels in first morning urine samples from postpartum, fully breast-feeding women to characterize the reemergence of these urinary hormones after pregnancy ovarian quiescence and early postpartum period and to determine whether follicle regulatory protein could be used prospectively to predict the return of fertility. STUDY DESIGN: Twenty-five hundred urine samples collected from six postpartum women were evaluated. Daily urine samples collected from normally cycling women were used to establish normal urinary hormone and hormone metabolite cyclicity. Luteinizing hormone, estrone-3-glucuronide, and pregnanediol-3-glucuronide levels were measured by radioimmunoassay. Follicle regulatory protein level was assayed with a double-antibody enzyme-linked immunosorbent assay. RESULTS: Although follicle regulatory protein levels were found to be very low or undetectable in early postpartum urine, they began to rise with episodes of estrone-3-glucuronide and pregnanediol-3-glucuronide secretion. A chi 2 analysis suggests that increasing urinary follicle regulatory protein levels are most closely associated with the luteal phase of the first menstrual cycles in postpartum women. CONCLUSIONS: These results suggest that follicle regulatory protein is of little value in predicting either the onset of renewed ovarian activity or the fertile period. PMID- 1442920 TI - Immunolocalization of the vasoconstrictor endothelin in human endometrium during the menstrual cycle and in umbilical cord at birth. AB - OBJECTIVE: Our objective was to determine the localization of immunoreactive endothelin in human cyclic endometrium and in umbilical cord during normal delivery and after cesarean section. STUDY DESIGN: Fixed dated endometrial tissue (n = 41) and umbilical cord (n = 6) were subjected to immunohistochemistry with an antiserum cross reacting with endothelin-1, -2 and -3. RESULTS: Low levels of stromal endometrial staining were seen throughout the cycle. The strongest staining was in luminal epithelium throughout the secretory phase and in glandular epithelium in the late-secretory phase. In umbilical cord the most intense immunoreactivity was present on the amnion cells on the outer cord, with some staining in intermittent cells in the Wharton's jelly and in umbilical vein cells. No differences were detected between cord from normal delivery or cesarean section. CONCLUSION: A paracrine role is suggested for endothelin in regulation of endometrial function and a role in vasoconstriction in the umbilical cord at birth. PMID- 1442921 TI - Reduced platelet tritium-labeled imipramine binding sites in women with premenstrual syndrome. AB - OBJECTIVE: We studied the possible role of serotonergic systems in the cause of premenstrual affective symptoms. STUDY DESIGN: The binding of tritium-labeled imipramine to platelets is thought to parallel central nervous system binding and to indicate serotonergic activity. We measured platelet tritium-labeled imipramine binding sites in the follicular and luteal phases in 12 controls and in 9 women with well-documented late luteal phase dysphoric disorder. In statistical analyses we used repeated measures analysis of variance, with Student Newman-Keuls and Duncan's one-tailed t tests, and Pearson's r. RESULTS: The values of subjects with late luteal phase dysphoric disorder were lower than those of controls (F [1,39] = 5.13, p = 0.03). Both follicular and luteal phase level were lower in subjects with late luteal phase dysphoric disorder but reached statistical significance only in the follicular phase. CONCLUSION: Lower platelet tritium-labeled imipramine binding in women with late luteal phase dysphoric disorder supports the hypothesis that alteration of central serotonergic systems may contribute to premenstrual dysphoric symptoms. PMID- 1442922 TI - The development of ultradian rhythms in the human fetus. AB - OBJECTIVE: Our objective was to determine the normal sequence of neurobehavioral development in the human fetus between 14 weeks' gestation and delivery. STUDY DESIGN: The study was performed by longitudinal ultrasonographic observation of 45 low-risk singleton fetuses. RESULTS: During the first half of the midtrimester there was a high rate of spontaneous movement that appeared randomly distributed. By the end of that trimester an increase in the duration of intervals of quiescence resulted in activity appearing cyclically distributed, with the duration of quiet cycles progressively increasing to term. Fetal mouthing and breathing were linked with cyclic behavior from the time of their emergence. Fetal heart rate pattern A could be recognized from around 32 weeks, due to a reduction in baseline variability in quiet cycles after 30 weeks, whereas pattern B could be recognized several weeks earlier. From the time cyclic behavior and heart rate patterns could be recognized, intervals of coincidence of the fetal behavioral state variables increased progressively with advancing gestation. PMID- 1442923 TI - Effect of calcitonin gene-related peptide on the uterine vasculature of the nonpregnant ewe. AB - OBJECTIVES: The current study was designed to evaluate the uterine vascular effects of calcitonin gene-related peptide on the uterine vasculature of nonpregnant sheep and compare them with the effects of prostacyclin. STUDY DESIGN: Five nonpregnant oophorectomized ewes were instrumented with uterine and pulmonary artery flow probes and catheters. Dose-response curves were constructed according to increasing doses of calcitonin gene-related peptide (0.01, 0.03, 0.1, 0.3, 1, and 3, micrograms/min) and prostacyclin (0.03, 0.1, 0.3, 1, 3, and 10 micrograms/min) via 10-minute uterine artery infusions. RESULTS: Both calcitonin gene-related peptide and prostacyclin produced a significant increase in uterine blood flow and a decrease in uterine vascular resistance. Calcitonin gene-related peptide was found to be approximately 17 times more potent than prostacyclin as a vasodilator. Local uterine artery infusions of calcitonin gene related peptide led to significant increases in heart rate but did not alter blood pressure, cardiac output, or total peripheral resistance at the doses tested. In contrast, at doses of prostacyclin that produced similar uterine vasodilatation, prostacyclin led to significant decreases in systemic arterial blood pressure and total peripheral resistance and increases in heart rate and cardiac output. CONCLUSION: These data strongly suggest that calcitonin gene related peptide, an endogenously occurring vasoactive peptide, could play an important role in regulating uterine and systemic hemodynamics. PMID- 1442924 TI - An ultrastructural study of the developing urogenital tract in early human fetuses. AB - OBJECTIVES: This study examines the gonoducts during the ambisexual stage of human fetal development to define their ultrastructural characteristics, including the origin and antomic relationship of the mesonephric and paramesonephric ducts during gonoductal development. STUDY DESIGN: The reproductive tracts from five fetuses ranging in gestational age from 35 to 45 days were processed for ultrastructural examination. The developing mesonephric ducts, paramesonephric ducts, and their surrounding mesenchyme were studied with a Phillips 300 transmission electron microscope. RESULTS: The mesonephric ducts and paramesonephric ducts have distinctive cytoplasmic and cell surface ultrastructural characteristics, as well as different morphologic patterns of epithelial-mesenchymal interaction. Cephalad portions of mesonephric ducts and paramesonephric ducts are separated by mesenchyme, but more caudal aspects move progressively closer until they are juxtaposed but separate. CONCLUSIONS: Early mesonephric ducts and paramesonephric ducts may be distinguished because of their distinctive ultrastructural features; epithelial-mesenchymal interaction may be important in their differentiation and maintenance; both gonoducts retain their morphologic identity throughout, supporting their separate origins. PMID- 1442925 TI - Ethically justified guidelines for family planning interventions to prevent pregnancy in female patients with chronic mental illness. AB - OBJECTIVE: This article proposes ethically justified clinical guidelines for family planning interventions to prevent pregnancy in female patients. STUDY DESIGN: We reviewed literature on family planning and consequences of pregnancy in patients with chronic mental illness and related that literature to ethical principles. RESULTS: Patients with chronic mental illness are ethically unique because they have chronically and variably impaired autonomy. Existing guidelines and proposals for family planning interventions for mentally retarded patients are shown not to apply to such patients. CONCLUSION: Three sets of guidelines for three groups of patients, representing the continuum of chronically and variably impaired autonomy, are proposed: (1) a set of guidelines for patients who can achieve thresholds of autonomy, (2) a set of guidelines for patients irreversibly near thresholds of autonomy, and (3) a set of guidelines for patients irreversibly below thresholds of autonomy. These guidelines should contribute significantly to the quality of obstetric and gynecologic care for female patients with chronic mental illness. PMID- 1442926 TI - Activation of protein kinase C stimulates collagenase production by cultured cells of the cervix of the pregnant guinea pig. AB - OBJECTIVE: Dilatation of the uterine cervix at parturition is achieved by an estrogen-induced, collagenase-mediated degradation of type I collagen in the cervix. The objective was to test the hypothesis that collagenase production in the cervix of pregnant guinea pig in culture is mediated by activation of protein kinase C. STUDY DESIGN: The effects of 17 beta-estradiol, prostaglandin F2 alpha, or activation of protein kinase C by phorbol-12-myristate-13-acetate, 1-stearoyl 2-arachidonyl-sn-glycerol and phospholipase C on collagenase production was studied with primary monolayer cultures of cervical cells from Hartley guinea pigs at 50 days' gestation. Results are analyzed for statistical significance with analysis of variance. RESULTS: Collagenase production is increased twofold to threefold by 17 beta-estradiol, prostaglandin F2 alpha, or activation of protein kinase C. The observed stimulation of collagenase production by 17 beta estradiol and prostaglandin F2 alpha was blocked by the protein kinase C inhibitor 1-(5-isoquinoline sulfonyl) 2-methylpiperazine dihydrochloride. CONCLUSION: Collagenase production in cultured cervical cells of pregnant guinea pig is stimulated by activation of protein kinase C. PMID- 1442927 TI - Hydrogen peroxide and reoxygenation cause prostaglandin-mediated contraction of human placental arteries and veins. AB - OBJECTIVE: Because our previous studies in several vascular preparations suggest that posthypoxic reoxygenation elicits tone responses by generation of hydrogen peroxide we compared the actions of reoxygenation and hydrogen peroxide on isolated human placental arteries and veins. STUDY DESIGN: Endothelium-intact and denuded arteries and veins (1 to 2 mm diameter, from normal term deliveries), incubated under 95% oxygen/5% carbon dioxide or 5% oxygen/5% carbon dioxide (balance nitrogen) and precontracted with 1 to 10 nmol/L U46619, were exposed to hypoxia (95% nitrogen/5% carbon dioxide, PO2 8 to 10 torr) followed by reoxygenation and to 1 to 100 mumol/L hydrogen peroxide in the presence and absence of the inhibitor of prostaglandin biosynthesis, 10 mumol/L indomethacin. RESULTS: In both arteries and veins posthypoxic reoxygenation or exposure to hydrogen peroxide produced vascular contraction that was eliminated or reversed to a modest relaxation by indomethacin, consistent with mediation by prostaglandins. Hypoxia after incubation with 5% oxygen, but not 95% oxygen, caused a modest prostaglandin-independent relaxation. Removal of the endothelium did not alter any of these responses. CONCLUSION: Placental arteries and veins show a similar prostaglandin-mediated contraction to hydrogen peroxide and posthypoxic reoxygenation, consistent with a possible involvement of hydrogen peroxide in the response to reoxygenation. PMID- 1442928 TI - Changes in expression of the cyclooxygenase gene in human fetal membranes and placenta with labor. AB - OBJECTIVE: Our objective was to examine the expression of the gene coding for cyclooxygenase, the central enzyme in prostaglandin synthesis, in human placenta and fetal membranes during pregnancy and before and after labor at term. STUDY DESIGN: Expression of the gene for cyclooxygenase was examined with Northern hybridization to ribonucleic acid from human placenta throughout pregnancy and human amnion and chorion decidua in the late third trimester. RESULTS: Expression was undetectable in trophoblast during the first and second trimesters. Expression in amnion and trophoblast increased 3.5- and 2.5-fold, respectively, in association with labor. CONCLUSIONS: Our results suggest that the increase in prostaglandin synthesis within the uterus that is seen with the onset of labor is associated with an increase in the expression of the gene cyclooxygenase. PMID- 1442929 TI - A novel change in cytologic localization of human chorionic gonadotropin and human placental lactogen in first-trimester placenta in the course of gestation. AB - Cytologic localization of human chorionic gonadotropin and human placental lactogen in developing human early placenta was analyzed by avidin-biotin immunoperoxidase techniques with an affinity-purified polyclonal antibody to beta human chorionic gonadotropin carboxyl terminal peptide and a polyclonal antibody to human placental lactogen. In 4- to 5-week placentas human chorionic gonadotropin and human placental lactogen were found to be primarily localized to cytotrophoblasts, whereas in 6- to 12-week placentas these substances were exclusively localized to syncytiotrophoblast. We previously reported that a similar change in cytologic localization of epidermal growth factor and its receptor from cytotrophoblasts to syncytiotrophoblast in first-trimester placenta appeared between 5 and 6 weeks of gestation. Because epidermal growth factor was demonstrated to stimulate human chorionic gonadotropin and human placental lactogen production by early placental tissues, their simultaneous expression, as well as epidermal growth factor and its receptor in the cytotrophoblast of 4- to 5-week placenta and in the syncytiotrophoblast of 6- to 12-week placenta, implies that human chorionic gonadotropin and human placental lactogen production by first-trimester placenta may be regulated in an autocrine manner, wherein epidermal growth factor may serve as the signal. These findings suggest that in very early placenta, before 6 weeks of gestation, no sequential expression of human chorionic gonadotropin and human placental lactogen closely linked to syncytia formation may exist and that both can be expressed in the cytotrophoblast or undifferentiated stem cell of villous trophoblast in very early placenta. PMID- 1442930 TI - Transforming growth factor-beta opposes the stimulatory effects of interleukin-1 and tumor necrosis factor on amnion cell prostaglandin E2 production: implication for preterm labor. AB - OBJECTIVE: In preterm labor increased concentrations of interleukin-1 and tumor necrosis factor are present in amniotic fluid. These cytokines may promote labor by stimulating the production of prostaglandins by intrauterine tissues. In many biologic processes, transforming growth factor-beta modifies the actions of cytokines. We studied the effect of transforming growth factor-beta on the cytokine-induced prostaglandin E2 production by amnion cells. STUDY DESIGN: Human amnion cells in monolayer culture were treated with interleukin-1, tumor necrosis factor, or vehicle in the presence or absence of transforming growth factor-beta. The prostaglandin E2 production was measured. RESULTS: Transforming growth factor beta decreased the interleukin-1- or tumor necrosis factor-induced prostaglandin E2 production by 70% to 80% and the basal prostaglandin E2 synthesis by 27%. The synergistic stimulation of prostaglandin E2 production by the combination of interleukin-1 with tumor necrosis factor was inhibited by 80% in cells treated with transforming growth factor-beta. Transforming growth factor-beta 1, -beta 2, and -beta 1,2 were equipotent. CONCLUSION: Transforming growth factor-beta suppresses the cytokine-induced prostaglandin E2 production by amnion cells and may be an important factor in maintaining pregnancy in the face of labor promoting cytokines. PMID- 1442931 TI - Mutations of the Ki-ras oncogene in endometrial carcinoma. AB - OBJECTIVE: The purpose of this study was to assess the extent of involvement of the ras oncogene in endometrial carcinoma. STUDY DESIGN: Genomic deoxyribonucleic acid from 30 samples of endometrial carcinoma was examined for point mutations in codons 12, 13, and 61 from the Ha-ras, Ki-ras, and N-ras genes by means of the polymerase chain reaction, slot-blotting, and deoxyribonucleic acid sequencing procedures. RESULTS: An apparent somatic mutation of Ki-ras codon 12 in one of 10 paraffin-embedded tumors was confirmed by deoxyribonucleic acid sequence analysis. Two of 20 frozen endometrial carcinoma specimens were also shown to contain a point mutation in Ki-ras codon 12. No correlation between ras mutation and a number of histologic or clinical parameters was observed. CONCLUSIONS: These data suggest a potential role for Ki-ras codon 12 mutations in the development of some (10%) endometrial cancers. PMID- 1442932 TI - Effect of maternal oxygen administration on fetal oxygenation during graded reduction of umbilical or uterine blood flow in fetal sheep. AB - OBJECTIVE: Effects of maternal oxygen administration on fetal blood gases and on oxygen delivery and consumption during reduced uterine and reduced umbilical blood flows were examined. STUDY DESIGN: In eight pregnant sheep (gestational age 133 +/- 4 days) flow transducers were applied to a uterine and the common umbilical artery. Graded reductions in uterine and umbilical blood flows were achieved by a hypogastric artery snare and a balloon cuff encircling the umbilical cord. Fetal femoral arterial and umbilical venous oxygen contents and flows were measured at varying flow reductions with the ewe breathing air or oxygen. RESULTS: During 75% reduction in umbilical blood flow maternal oxygen administration significantly increased fetal oxygen delivery (6.4 +/- 2.5 to 7.7 +/- 2.3 ml/min/kg) and oxygen consumption (4.3 +/- 1.2 to 5.0 +/- 0.8 ml/min/kg). With similar reduction of uterine flow oxygen administration increased oxygen delivery from 8.3 +/- 2.4 to 12.3 +/- 3.6 and oxygen consumption from 3.3 +/- 0.8 to 4.7 +/- 1.6 ml/min/kg. CONCLUSION: Maternal oxygen inhalation improves fetal oxygenation during umbilical but especially during uterine blood flow reduction. PMID- 1442933 TI - Convulsions in pregnancy in related gorillas. AB - Two related gorillas, the second the granddaughter of the first, had pregnancies complicated by convulsions and edema. They may have suffered from eclampsia, indicating that this is not an exclusively human disease and that in gorillas, as in humans, there is a familial factor. PMID- 1442934 TI - Messenger ribonucleic acid for transforming growth factor-alpha, but not for epidermal growth factor, is expressed in fetal and neonatal mouse brain. AB - OBJECTIVE: Little is known concerning the presence of transforming growth factor alpha in fetal and neonatal tissues. Our objective was to analyze messenger ribonucleic acid expression for transforming growth factor-alpha and epidermal growth factor, the structural and biochemical analog of transforming growth factor-alpha in fetal and neonatal murine brain. STUDY DESIGN: Messenger ribonucleic acid was prepared from whole brains of mice from these developmental stages: embryonic days 14, 15, and 17, postnatal days 0, 4, 10, and adult. Polymerase chain reaction was performed on the complementary deoxyribonucleic acid obtained from reverse transcription of messenger ribonucleic acid with transforming growth factor-alpha and epidermal growth factor primers. In addition, ribonuclease protection assay was used to identify transforming growth factor-alpha transcripts. RESULTS: We found messenger ribonucleic acid encoding transforming growth factor-alpha in all stages of development used. Epidermal growth factor messenger ribonucleic acid was not found in any stage. Ribonuclease protection assay confirmed transforming growth factor-alpha transcripts in these tissues. CONCLUSION: Transforming growth factor-alpha may play an autocrine or paracrine role in the differentiation or maintenance of murine fetal and neonatal brains. PMID- 1442935 TI - Cardiac electromechanical dissociation in the hypoxic fetal sheep may have clinical implications. AB - OBJECTIVES: Our purpose was to determine the sequence of fetal cardiac electrical and mechanical events associated with acute hypoxic acidemia and to correlate those events with terminal fetal heart rate patterns preceding fetal death. STUDY DESIGN: Eight acutely catheterized fetal sheep were rendered hypoxic by placental embolization with microspheres until fetal death occurred. The fetal electrocardiogram, Doppler cardiogram, left ventricular and aortic pressures, and fetal heart rate were continuously recorded. RESULTS: All eight fetuses showed a terminal bradycardia consisting of two phases: an initial phase of falling ventricular pressures, culminating in mechanical asystole, and a subsequent phase after asystole during which the electrocardiographic signal persisted for an average duration of 15.2 +/- 8.7 minutes (range 3.1 to 32.4) and triggered a Hewlett-Packard 8040A monitor to show a heart rate pattern. CONCLUSIONS: The phenomenon of cardiac electromechanical dissociation may be occurring during similar terminal bradycardias that are observed in human labor and explains the delivery of a fresh stillbirth in spite of the recording of an electrocardiographic signal from a scalp electrode. PMID- 1442936 TI - The fetus as an allograft: immunobiologic role of human trophoblasts for fetal survival. AB - OBJECTIVE: The hypothesis of this study is that trophoblasts contribute to the survival of the mammalian fetal allograft. STUDY DESIGN: Immunologic and molecular biologic studies were performed with human trophoblasts or trophoblastic tumor cells to investigate the expression of class I human leukocyte antigens, the susceptibility to natural killer and lymphokine-activated cells, the ontogeny of Fc gamma-receptors, and the production of immunosuppressive factors. RESULTS: Heterogeneous expression of class I human leukocyte antigens on trophoblasts was regulated at transcriptional level. Trophoblasts showed low susceptibility to natural killer and lymphokine-activated cells. Trophoblasts expressed natural killer cell-type Fc gamma-receptor III, which mediates phagocytosis. The trophoblast-derived immunosuppressive factor was very similar to transforming growth factor-beta. CONCLUSION: The trophoblasts, which ultimately form the fetoplacental interface, constitute a major immune barrier for the survival of the allogenic conceptus. PMID- 1442937 TI - Suppression of natural killer cell activity by sera from patients with endometriosis. AB - OBJECTIVE: We determined the effect of sera from patients who have endometriosis on natural killer cell activity. STUDY DESIGN: The natural killer cell activity of lymphocytes from healthy volunteers was examined after incubation with sera from patients who had endometriosis or from controls, with K562 cells used as targets. RESULTS: Lymphocytes treated with sera from patients who had endometriosis expressed significantly lower levels of cytotoxicity compared with lymphocytes treated with control sera. This suppression of cytotoxicity was dose dependent, and the degree of suppression was proportional to the incubation time of the effector cells with the sera. Decreased cytotoxicity after serum treatment was also observed with sera from patients who had been treated with danazol. CONCLUSIONS: These findings show that humoral factors that can inhibit natural killer cell activity in vitro are present in the peripheral blood of patients who have endometriosis; moreover, they suggest that the suppressed natural killer cell activity may allow the development of endometrial cells at ectopic sites. PMID- 1442938 TI - A prospective, controlled multicenter study on the obstetric risks of pregnant women with antiphospholipid antibodies. AB - OBJECTIVES: A prospective, controlled multicenter study was performed to estimate the obstetric risks of antiphospholipid antibodies (the lupus anticoagulant and anticardiolipin antibodies). In addition, the risks of prior thrombosis, obstetric history, systemic lupus erythematosus, and high-dose prednisone treatment were evaluated. STUDY DESIGN: After screening for antiphospholipid antibodies in patients with lupus erythematosus or women with prior fetal loss(es), 59 subsequent pregnancies with and 54 without these antibodies were followed. RESULTS: The presence of the lupus anticoagulant and a history of at least three spontaneous abortions could predict fetal loss (p = 0.032 and 0.001, respectively). In live born infants, a low birth weight could be predicted by the presence of anticardiolipin antibodies (p = 0.034), prior intrauterine fetal death (p = 0.025), and treatment with high-dose prednisone (p = 0.002). No relationships were seen between antiphospholipid antibodies and small-for gestational-age newborns and pregnancy-induced hypertension or preeclampsia. The disappearance of antiphospholipid antibodies during pregnancy was not correlated with live birth. CONCLUSION: It is concluded that the presence of antiphospholipid antibodies is a risk factor for adverse pregnancy outcome. PMID- 1442939 TI - Significance of peritoneal macrophages on fertility in mice. AB - OBJECTIVE: To elucidate the role of peritoneal macrophages in infertility, we investigated how the presence of peritoneal macrophages would affect fecundity in mice. Moreover, we also studied the effects of interleukin-1 on embryonic development. STUDY DESIGN: Mice were administered OK-432 intraperitoneally to induce macrophage infiltration of the peritoneal cavity; ovulation was then induced and animals were mated. On day 13 of gestation, fetuses were counted. After injection of OK-432 or interleukin-1, the mice were mated. Three days later, embryos were collected and the stage of embryo development was determined. RESULTS: In mice given OK-432 (n = 33), four (12%) became pregnant and the mean litter number was 6.0 +/- 3.6, whereas in the control group 23 of 30 mice (77%; p < 0.01) became pregnant and the litter number was 14.1 +/- 5.3 (p < 0.01). OK-432 and interleukin-1 administered intraperitoneally significantly suppressed embryo development (p < 0.01). CONCLUSION: Increased numbers of peritoneal macrophages negatively affect fecundity, probably by suppressing embryonic development. PMID- 1442940 TI - Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis. AB - OBJECTIVE: Our aim was to examine the relationship between the levels of cytokines in peritoneal fluid and its embryo toxicity. STUDY DESIGN: The levels of interleukin-1 and tumor necrosis factor were measured in peritoneal fluid from infertile women who did not have endometriosis (n = 21), who had untreated endometriosis (n = 19), and who had undergone medical treatment for endometriosis (n = 10). Embryo toxicity was investigated in mouse two-cell embryos cocultured with the oviducts in culture media that contained various concentrations of peritoneal fluid. RESULTS: The levels of cytokines were significantly higher in the peritoneal fluid from women who had untreated endometriosis than in women who did not have endometriosis, but they were extremely low in women who had undergone medical treatment with either danazol or buserelin. The peritoneal fluid from women who had untreated endometriosis adversely affected the cleavage of mouse two-cell embryos. After medical treatment the embryo toxicity of the peritoneal fluid was almost undetectable. CONCLUSION: These results offer some theoretic bases in support of medical treatment to improve reproductive performance in infertile women who have endometriosis. PMID- 1442941 TI - Luteinized unruptured follicle in the early stages of endometriosis as a cause of unexplained infertility. AB - OBJECTIVE: We attempted to clarify the relationship between luteinized unruptured follicle, which occurs in the early stages of endometriosis, and unexplained infertility. STUDY DESIGN: Seventy patients who had unexplained infertility were reviewed. RESULTS: Laparoscopic examination showed that 47 patients (67%) had endometriosis; of these, 40 (85%) had minimal or mild disease. The incidence of luteinized unruptured follicle was higher (p < 0.05) in patients who had endometriosis (35%/patient and 25%/cycle) compared with patients who did not have endometriosis (11%/patient and 7%/cycle). Degenerated oocyte cumuli were collected in 6 (43%) of 14 luteinized unruptured follicles diagnosed by transvaginal ultrasound. CONCLUSIONS: These results show that luteinized unruptured follicle is common in patients who have mild or minimal endometriosis and that it may be one of the causes of endometriosis-associated infertility. Transvaginal ultrasound-guided follicular puncture of luteinized unruptured follicle during the mid luteal phase may be useful in establishing a definitive diagnosis of luteinized unruptured follicle. PMID- 1442942 TI - Luteal function in infertile patients with endometriosis. AB - OBJECTIVE: Our purpose was to determine whether infertile patients who have endometriosis show luteal phase defects. STUDY DESIGN: The luteal function in 24 infertile patients who had endometriosis was compared with the luteal function in 20 patients who had unexplained infertility and did not have endometriosis (control). In both groups serum luteinizing hormone, follicle-stimulating hormone, progesterone, and estradiol were assayed every day throughout the menstrual cycle. Endometrial biopsy specimens were obtained from eight patients of the endometriosis group for histologic dating of the endometrium. RESULTS: No significant differences in progesterone levels were observed between these two groups during the mid and late luteal phase. Seven of the eight patients who underwent histologic dating showed a luteal phase pattern, whereas only one patient was out of phase. CONCLUSION: Infertile patients who have endometriosis do not always have luteal phase defects. PMID- 1442943 TI - The impact of endometriosis on the reproductive outcome of infertile patients. AB - OBJECTIVE: We examined whether the presence and severity of endometriosis affect the reproductive outcome of infertile patients. STUDY DESIGN: The conception rates of 2080 infertile women, 1263 who had endometriosis and 817 who did not have endometriosis, were analyzed retrospectively by means of the chi 2 test. Depending on the stage of the disease patients who had endometriosis-associated infertility underwent expectant management, danazol therapy, or minor or major conservative surgery. The patients who failed to conceive after these conventional treatments were enrolled in the in vitro fertilization-embryo transfer program. RESULTS: The conception rates were virtually identical regardless of the presence or absence of endometriosis (30.7% vs 30.0%). The outcome of in vitro fertilization-embryo transfer was not affected either by the presence or the severity of the disease. CONCLUSION: Endometriosis had no impact on the reproductive outcome of infertile patients in this series unless the anatomy of the pelvic organs was heavily distorted, which can occur in the advanced stages of the disease. PMID- 1442944 TI - Myocardial necrosis in a newborn after long-term maternal subcutaneous terbutaline for suppression of premature labor. PMID- 1442945 TI - Fetal choroid plexus cysts and trisomy 18. PMID- 1442946 TI - Laser therapy for intraepithelial cancer of the vagina. PMID- 1442947 TI - Initiation of antepartum testing in the hypertensive gravid woman. PMID- 1442948 TI - Legal thoughts on malpractice claims: causes and prevention. PMID- 1442949 TI - Laparoscopic hysterectomy: reinventing the wheel? PMID- 1442950 TI - Term birth after midtrimester hysterotomy and selective delivery of an acardiac twin. AB - OBJECTIVE: Our aim was to determine whether hysterotomy and selective removal of an acardiac twin could improve the outcome of the "pump" twin. STUDY DESIGN: A literature and case review of the outcome of the acardiac twin malformation was performed. When an acardiac malformation was diagnosed at 19 weeks' gestation the patient was monitored with weekly ultrasonographic examinations. At 23 weeks' gestation, no blood flow could be demonstrated to the acardiac twin and it was thought that the continued presence of the acardiac twin posed a risk to the "pump" twin. A midtrimester hysterotomy was performed and the acardiac twin was delivered. RESULTS: After the midtrimester hysterotomy, the pregnancy progressed to term and a healthy female infant was delivered by elective cesarean section at 37 weeks' gestation. CONCLUSION: Midtrimester hysterotomy may be a useful intervention in cases of twinning when one fetus is a threat to the health of the other. PMID- 1442951 TI - Idiopathic myelofibrosis in pregnancy: a case report and review of the literature. AB - Idiopathic myelofibrosis is a rare myeloproliferative disorder characterized by excessive accumulation of connective tissue in the bone marrow in association with anemia, splenomegaly, and extramedullary hematopoiesis. The cause of this disease is unknown, and the prognosis is generally poor. To our knowledge, this is the first case report of a patient with idiopathic myelofibrosis who carried a term pregnancy. In spite of the increased perinatal risks, a favorable outcome was possible with close antepartum surveillance. PMID- 1442952 TI - Oral contraceptive use and the incidence of cervical intraepithelial neoplasia. AB - OBJECTIVE: Our objective was to examine the relationship between oral contraceptive use and the incidence of cervical intraepithelial neoplasia. STUDY DESIGN: In a prospective follow-up study of 6622 women participating in the Second Tromso Study conducted in 1979 and 1980 in Tromso, Norway, women aged 20 to 49 years answered a questionnaire regarding their smoking history, dietary habits, alcohol consumption, and oral contraceptive use. They were then followed for 10 years with data from the Pathology Registry of the University Hospital. RESULTS: The age-adjusted incidence rate of cervical intraepithelial neoplasia was 897 per 100,000 person years among noncurrent and 1295 per 100,000 person years among current oral contraceptive users as of 1979. After adjusting for age, marital status, smoking, and frequency of alcohol intoxication the relative rate for current users was 1.5 (95% confidence interval 1.1 to 2.1), and the relative rate for past users was 1.4 (95% confidence interval 1.0 to 1.8), as compared with those who had never used oral contraceptives before 1979. CONCLUSION: These findings support the hypothesis that the occurrence of cervical intraepithelial neoplasia is increased by oral contraceptive use. PMID- 1442953 TI - Calcium homeostasis in pregnant women receiving long-term magnesium sulfate therapy for preterm labor. AB - OBJECTIVES: The hypothesis of this study is that calcium homeostasis and bone mineralization are altered in pregnant women receiving long-term therapy with magnesium sulfate as compared with similar women not receiving magnesium sulfate to control preterm labor. STUDY DESIGN: Thirty-nine women between 24 and 32 weeks' gestation, matched for age, race, and duration of bed rest, were enrolled. Indices of calcium homeostasis in serum and urine were measured serially, and bone mineralization of the distal radius was measured at 1 and 11 weeks post partum. RESULTS: Magnesium therapy was administered for a mean duration of 26 +/- 14 days and a cumulative dose of 1405 +/- 963 gm. Serum concentrations of magnesium, phosphorus, and parathyroid hormone increased and those of calcium decreased from baseline values in the magnesium sulfate group and remained uniform throughout the 3-week investigation. The serum magnesium, phosphorus, parathyroid hormone, and calcium concentrations in the control group were unchanged during the study and differed significantly from those in the magnesium sulfate group (p < 0.001). Urinary output of magnesium, calcium, and copper was significantly greater in the magnesium sulfate group than in the control group throughout the study. Urinary losses of calcium in the magnesium sulfate group, approximately 800 to 900 mg/day, were substantial. Although radius bone density 1 week post partum did not differ between groups, the change in bone density from 1 to 11 weeks post partum was significantly lower in the magnesium sulfate group than in controls. CONCLUSIONS: These data suggest that calcium homeostasis is altered during and after long-term magnesium sulfate therapy. The marked, prolonged urinary calcium losses may affect maternal bone mineralization. PMID- 1442954 TI - Nifedipine for treatment of preterm labor: a historic prospective study. AB - OBJECTIVES: The purpose of this study was to ascertain whether adverse fetal and/or neonatal effects occurred during nifedipine treatment of preterm labor and to assess maternal tolerance of nifedipine therapy in patients intolerant of a beta-sympathomimetic agent. STUDY DESIGN: We undertook historic prospective review of medical records of 102 women admitted to an antepartum ward for treatment of preterm labor who received nifedipine. Data were collected regarding maternal side effects, fetal surveillance, and neonatal outcome. RESULTS: The number and severity of reported maternal side effects were significantly reduced when patients were switched from terbutaline to nifedipine. No discontinuance of nifedipine occurred because of maternal side effects. Fetal surveillance testing and neonatal outcome data failed to reveal deleterious in utero effects of nifedipine. CONCLUSIONS: Nifedipine was a well-tolerated and safe tocolytic in this population and warrants further investigation. PMID- 1442955 TI - Nonimmune hydrops fetalis associated with maternal infection with syphilis. AB - Intrauterine infection with syphilis was diagnosed by reactive maternal serologic studies, ultrasonographic findings, and exclusion of other causes in three hydropic fetuses at 31, 34, and 35 weeks' gestation. With penicillin therapy and preterm delivery all infants survived through the perinatal period. Intrauterine infection that follows syphilis is a potentially treatable cause of nonimmune hydrops. PMID- 1442956 TI - Suppression of 24-hour cholecystokinin secretion by oral contraceptives. AB - Weight gain is a common side effect during oral contraceptive use. The secretion of the satiety hormone cholecystokinin was recorded for 24 hours in women before and during treatment with oral contraceptives. During treatment serum profiles of cholecystokinin were clearly suppressed, which might be related to increased appetite and weight gain. PMID- 1442957 TI - Delayed endometrial maturation induced by daily administration of the antiprogestin RU 486: a potential new contraceptive strategy. AB - OBJECTIVE: Our objective was to determine if a progesterone antagonist might interdict the development of a secretory endometrium. STUDY DESIGN: Eleven normally cycling women not at risk for pregnancy received RU 486 (1 mg/day orally) or placebo throughout one menstrual cycle in a randomized, double-blind, crossover fashion. Estradiol, progesterone, and placental protein 14 were measured every 3 days; luteinizing hormone was measured until the midcycle surge was detected. An endometrial biopsy was performed on luteal phase day 7 to 9 and interpreted with Noyes' criteria. Differences between treatment groups were analyzed by the Student t test. RESULTS: RU 486 delayed ovulation, retarded endometrial maturation, and reduced peak levels of placental protein 14 without affecting gonadal steroid production. The abnormalities in endometrial morphology and function are similar to those seen in infertile women with luteal phase defects. CONCLUSION: We hypothesize that this regimen of antiprogestin administration may prevent implantation and offer a novel strategy for fertility control. PMID- 1442958 TI - Antenatal tests of fetal welfare and development at age 2 years. AB - OBJECTIVE: Our objective was to examine the outcomes at 2 years of age of fetuses delivered electively before 34 weeks, studied antenatally with two tests of fetal well-being. STUDY DESIGN: Forty-two fetuses from high-risk pregnancies delivered electively by cesarean section before 34 weeks were stratified into normal versus abnormal subgroups with umbilical Doppler flow velocity waveform and fetal heart rate results. Developmental outcome was assessed at 2 years. Two comparison groups were also selected: 40 matched premature controls delivered spontaneously before 34 weeks and 67 normal babies delivered spontaneously at term. Frequency outcome data were tested with chi 2 analyses and the remainder with analyses of variance. RESULTS: Within the electively delivered study group poor cognitive progress at 2 years was more strongly associated with an abnormal fetal heart rate result than an abnormal Doppler result. Compared with the premature control and normal term groups, electively delivered fetuses were significantly delayed in growth, cognition, and motor development (p < 0.005). CONCLUSIONS: Adverse fetal welfare in a high-risk obstetric sample was associated with poorer outcome at 2 years. However, the whole of the group of fetuses from such high-risk pregnancies showed significant developmental delay compared with normal term children and, more importantly, matched premature infants delivered spontaneously from otherwise uncomplicated pregnancies. PMID- 1442959 TI - Macrosomia in postdates pregnancies: the accuracy of routine ultrasonographic screening. AB - OBJECTIVE: The purpose of this study was to assess the efficacy of routine ultrasonographic assessment of fetal weight in predicting fetal macrosomia in postdates pregnancies. STUDY DESIGN: A total of 519 pregnancies of > or = 41 weeks' duration were subjected to ultrasonographic estimation of fetal weight within 1 week of delivery. Estimated fetal weights were compared with birth weights. Linear regression analysis was performed and prediction limits for estimated fetal weights were generated. RESULTS: Twenty-three percent of infants had birth weights > or = 4000 gm and 4% had birth weights > or = 4500 gm. The mean percent absolute error was 7.7%. At a birth weight of > 3750 gm, the Hadlock model (which uses abdominal circumference and femur length) systematically overestimated the birth weight. The sensitivity, specificity, and positive and negative predictive values for the ultrasonographic diagnosis of macrosomia were 56%, 91%, 64%, and 87%, respectively. The prediction limits generated determine the range of birth weights predicted for a given estimated fetal weight. CONCLUSION: Routine ultrasonographic screening for macrosomia in postdates pregnancies is associated with a relatively low positive predictive value. PMID- 1442960 TI - Retrospective maternal mortality case ascertainment in West Virginia, 1985 to 1989. AB - OBJECTIVE: The death of women from pregnancy-related causes remains a threat to national maternal and child health. Maternal deaths as persistent, albeit rare occurrences are overlooked if vital registration systems are relied on to report such deaths. STUDY DESIGN: Live birth records were matched with death records for women of reproductive age to detect if a woman died within 1 year of delivery. The data for potential cases were reviewed by committee and classified as maternal and nonmaternal deaths. RESULTS: Of all linked birth-death records, 32% were related to pregnancy: 81% were directly related to pregnancy and 19% were indirectly related to pregnancy. The most frequent causes of death were hemorrhage and embolism. Thirty-eight percent of the women were transferred to tertiary hospitals before death. The case ascertainment through this study improved maternal death detection by 100% over official vital statistics. CONCLUSION: Enhanced maternal mortality surveillance increased the detection of maternal death in West Virginia. Case review of these deaths yielded important information useful in shaping the state's perinatal system. PMID- 1442961 TI - Laparoscopic diagnosis and repair of spigelian hernia: report of a case and technique. AB - Spigelian hernia is an uncommon hernia of the abdominal wall. We report a case of acquired spigelian hernia diagnosed and treated by laparoscopy. With more extensive use of laparoscopy to evaluate abdominal pain, the diagnosis of spigelian hernia can be made and repair accomplished without need for open exploratory surgery. PMID- 1442962 TI - Oligohydramnios and megacolon in a fetus with vesicorectal fistula and anal urethral atresia: a case report. AB - Severe oligohydramnios and extremely dilated bowel filled with hyperechogenic material floating in fluid were the ultrasonographic findings in a fetus at 27 weeks' gestation. Vesicorectal communication and urethral-anal atresia permitted urine to empty into the colon, causing megacolon, oligohydramnios, and markedly increased intraabdominal pressure resulting in pulmonary hypoplasia. PMID- 1442963 TI - Pathways to hysterectomy: insights from longitudinal twin research. AB - OBJECTIVE: We hypothesized that genetic influences act on "liability" to hysterectomy, that secular influences might differentially affect relative importance of genetic and environmental influences, and that the sources of genetic influences could be identified from reported risk factors. STUDY DESIGN: Hysterectomy data from an Australia-wide volunteer sample of female adult monozygotic and dizygotic twins are reported. In 1980 through 1982 a mailed questionnaire was completed by 1232 monozygotic female twin pairs and 751 dizygotic female twin pairs (3966 women) from the Australian Twin Register (wave 1). The same twins were surveyed by questionnaire 8 years later (wave 2). RESULTS: A total of 366 had undergone hysterectomy by wave 1 and a further 198 at wave 2. The twin-pair correlations for liability to hysterectomy at wave 1 (0.61 +/- 0.06 for monozygotic and 0.20 +/- 0.11 for dizygotic) and wave 2 (0.65 +/- 0.05 for monozygotic and 0.32 +/- 0.09 for monozygotic) indicated a substantial genetic contribution. Reported risk factors accounted for only 15% of total variance. CONCLUSION: Genetic influences on liability to hysterectomy were substantial and stable across birth cohorts, but the important sources of genetic influence on liability to hysterectomy are yet to be identified. PMID- 1442964 TI - Maternal and fetal hemodynamic effects of autologous blood donation during pregnancy. AB - OBJECTIVES: Our objectives were to describe the maternal and fetal hemodynamic impact of a 1 U acute blood loss during pregnancy and to compare the hemodynamic responses of pregnant women with those of nonpregnant controls. STUDY DESIGN: With Doppler techniques cardiac output and total peripheral vascular resistance were determined in 16 pregnant women in the third trimester and in 16 nonpregnant volunteers before and during orthostatic stress, before and after donation of 450 ml of whole blood. In pregnant women the fetal umbilical artery systolic/diastolic ratio was also determined. Data were subjected to multiple logistic regression analysis. RESULTS: In both groups orthostasis provoked significant decreases in cardiac output and increases in total peripheral vascular resistance. The hemodynamic effects of blood loss were less pronounced and did not significantly change the hemodynamic response to orthostasis in either group. Neither orthostasis nor blood loss caused significant changes in the umbilical systolic/diastolic ratio. CONCLUSION: These data support the hemodynamic safety of uncomplicated autologous blood donation during late pregnancy. PMID- 1442965 TI - First-trimester diagnosis of cystic hygroma--course and outcome. AB - OBJECTIVE: We studied the outcomes of fetuses in whom cystic hygroma was diagnosed in the first trimester of pregnancy through the application of transvaginal ultrasonography. STUDY DESIGN: In the period 1990 to 1991 22 fetuses with cystic hygroma were found. All fetuses had karyotyping and a complete ultrasonographic search for associated anomalies. RESULTS: Aneuploidy was found in seven of 22 fetuses: four trisomy 21, two trisomy 18, and one translocation. Monosomy X was absent in this series. In 15 of 22 cases there was a normal karyotype. In 10 of 15 euploid fetuses the small nonseptated hygroma resolved spontaneously. In four of 15 euploid fetuses other malformations were detected with ultrasonography (i.e., polycystic kidneys, coarctation of the aorta, bladder outlet obstruction, and fetal hydrops). CONCLUSION: Whenever a cystic hygroma is suspected in the antenatal period, even if of small size, a structured and detailed ultrasonographic examination and fetal karyotyping are recommended. PMID- 1442966 TI - Baking powder pica mimicking preeclampsia. AB - We report a case of baking powder pica during pregnancy that was associated with maternal hypertension, hypokalemia, and elevated liver function tests. After discontinuation of baking powder ingestion and correction of electrolyte abnormalities, the blood pressure and the liver function tests normalized. PMID- 1442967 TI - Sterilization needs in the 1990s: the case for quinacrine nonsurgical female sterilization. AB - Much evidence suggests that demand for sterilization is a function of supply of surgical sterilization services in less-developed countries. If such services were greatly expanded, the number of procedures performed would grow dramatically. While the prevalence of sterilization is estimated to increase from 23.5% to 28.8% of married women of reproductive age in the 1990s, there will actually be 106,432,000 more couples of reproductive age at the end of this decade than at its beginning who use either no method or a far less effective method with much lower continuation rates than sterilization--nearly a 20% increase. To achieve a mean sterilization prevalence of 47% of married women of reproductive age in the less-developed world, as now seen in the Republic of Korea and Puerto Rico, the number of sterilizations would need to be more than double the current projection for the 1990s: 328,429,000 rather than 159,000,000. The quinacrine pellet method for nonsurgical female sterilization offers hope that this enormous shortfall in sterilization services can be overcome in this decade. PMID- 1442968 TI - Predictors for live birth after unexplained spontaneous abortions: correlations between immunologic test results, obstetric histories, and outcome of next pregnancy without treatment. AB - Our objective was to determine whether results from tests for maternal serum antinuclear antibodies, cytotoxic antibodies to paternal lymphocytes, parental histocompatibility types, and blocking factors for maternal-paternal mixed lymphocyte reactions were predictive of pregnancy outcome without immunologic treatment. Pregnancy outcome data from 95 women with a history of unexplained recurrent spontaneous abortions who underwent immunologic tests at Jefferson Medical College were evaluated with multiple logistic regression analyses. The number of prior spontaneous abortions, history of another relevant diagnosis, parental sharing of one histocompatibility antigen, and maternal age were related to the outcome of the next pregnancy in women given no immunologic treatment (p = 0.05). No significant correlation was found between results from the immunologic tests or other history characteristics evaluated and outcome of the next pregnancy. The immunologic tests evaluated were not clinically useful predictors of pregnancy outcome. PMID- 1442969 TI - Cigarette smoking and urinary incontinence in women. AB - OBJECTIVE: The goal of this case control study was to evaluate the relationship between smoking and female urinary incontinence. STUDY DESIGN: The study included 606 women whose smoking histories were known; 322 were incontinent and 284 were continent. The condition(s) causing each subject's incontinence was determined by urodynamic testing; 40% of the continent subjects had the same testing. RESULTS: There were highly significant overall differences (p = 0.000009) in the distribution of current, former, and never smokers between incontinent (35%, 16%, 49%) and continent (24%, 8%, 68%) groups. The odds ratio for genuine stress incontinence was 2.20 for former (95% confidence interval 1.18 to 4.11) and 2.48 for current smokers (95% confidence interval 1.60 to 3.84); for motor incontinence it was 2.92 for former (95% confidence interval 1.58 to 5.39) and 1.89 (95% confidence interval 1.19 to 3.02) for current smokers. Increasing daily and lifetime cigarette consumption was associated with an increasing odds ratio for genuine stress incontinence but not for motor incontinence. The increased risk for incontinence was not due to differences in age, parity, weight, or hypoestrogenic status. CONCLUSION: The data establish a strong statistical relationship between current and former cigarette smoking and both stress and motor urinary incontinence in women. PMID- 1442970 TI - Natural history of chronic proteinuria complicating pregnancy. AB - OBJECTIVE: Although the significance of proteinuria is well-documented for pregnancy complicated by preeclampsia or diabetes, protein excretion of up to 300 mg per day is considered normal for uncomplicated pregnancy. Our purpose was to determine the significance of otherwise "asymptomatic" proteinuria identified during pregnancy. STUDY DESIGN: We reviewed the perinatal outcome of 65 pregnancies in 53 women with the following criteria: (1) proteinuria exceeding 500 mg per day, (2) no previously known renal disease, (3) no reversible renal dysfunction, and (4) no evidence for preeclampsia at discovery. RESULTS: Renal insufficiency coexisted in 62% of women, and 40% had chronic hypertension. Excluding 8 abortions, 53 (93%) of 57 pregnancies resulted in live infants; 45% of infants were delivered preterm and 23% had growth retardation. Of these 57 women, 62% demonstrated clinical evidence compatible with superimposed preeclampsia, and although the incidence of preeclampsia was increased with isolated proteinuria (29%), it was increased even more when there was associated chronic hypertension (incidence 100%) or renal insufficiency (incidence 58%). All 21 women who eventually underwent renal biopsy had histologic evidence of renal disease. To date, with only a limited follow-up of these 53 women, 11 (20%) have progressed to end-stage renal disease. CONCLUSION: "Asymptomatic" proteinuria is associated with a number of adverse pregnancy outcomes and serious long-term maternal morbidity. PMID- 1442971 TI - Selective pelvic and periaortic lymphadenectomy does not increase morbidity in surgical staging of endometrial carcinoma. AB - OBJECTIVE: The objective of this study was to retrospectively assess whether there was increased morbidity associated with the addition of selective pelvic and periaortic lymphadenectomy to hysterectomy in patients with endometrial carcinoma. STUDY DESIGN: From 1977 through 1988, 196 patients undergoing selective pelvic and periaortic lymphadenectomy plus hysterectomy were compared with 104 patients who underwent hysterectomy alone for endometrial adenocarcinoma. RESULTS: Only after adjusting for covariates was selective pelvic and periaortic lymphadenectomy associated with a higher estimated blood loss, which increased linearly with weight and was higher for black than for white women. The transfusion rate was similar for the two groups (selective pelvic and periaortic lymphadenectomy 6%, hysterectomy 10%). The mean blood loss was significantly different among the four gynecologic oncology surgeons (range 343 to 652 ml). The operating time primarily depended on patient weight and race, surgeon, and estimated blood loss. Postoperative hospital stay increased significantly with age, surgeon, wound infections, thrombotic events, and serious complications. Selective pelvic and periaortic lymphadenectomy had no effect on wound infections, which were directly related to operating time. Seventy-five (38%) of the selective pelvic and periaortic lymphadenectomy group and 19 (18%) of the hysterectomy group (p < 0.01) received whole-pelvic radiation with no difference in bowel complications (selective pelvic and periaortic lymphadenectomy 2/75, hysterectomy 1/19). The risk of serious complications was associated only with increasing age. CONCLUSION: Selective pelvic and periaortic lymphadenectomy in patients with endometrial carcinoma does not significantly add to morbidity from hysterectomy, which is related primarily to other factors such as patient weight, age, and race; operating time; and surgeon. PMID- 1442972 TI - Does DeLee suction at the perineum prevent meconium aspiration syndrome? AB - OBJECTIVE: We attempted to determine the impact of "early" (before delivery of the chest) oronasopharyngeal DeLee suctioning at the perineum in the prevention of meconium aspiration syndrome and to confirm that meconium aspiration syndrome is a postnatal event. STUDY DESIGN: We compared infants with meconium-stained fluid who underwent "early" oronasopharyngeal DeLee suctioning with a similar group of infants whose airways were suctioned "late" (after chest delivery). Practicing obstetricians did not know the study was being conducted by the pediatric staff, and an independent observer documented whether obstetricians performed "early" or "late" oronasopharyngeal DeLee suctioning. Immediate postnatal tracheal suctioning was performed in both groups. The study was conducted in a private tertiary care center averaging 5800 deliveries annually. A consecutive sample of 438 infants with meconium-stained fluid was analyzed. Of these infants, 221 received "early" oronasopharyngeal DeLee suctioning, while 217 infants were suctioned "late". RESULTS: Of the 438 infants with meconium-stained fluid, meconium aspiration syndrome developed in 38 (9%). These infants had higher rates of fetal distress (i.e., abnormal fetal heart rates) and lower Apgar scores (< or = 6) than infants without meconium aspiration syndrome (58% vs 17% and 65% vs 13%, respectively; p < 0.001). Forty-five percent of the infants with meconium aspiration syndrome had renal failure during the first 20 hours of life. In spite of "early" oronasopharyngeal DeLee suctioning, 53% of the infants in this group had meconium below the vocal cords and meconium aspiration syndrome developed in 7%. The time of oronasopharyngeal DeLee suctioning did not affect the rate of meconium aspiration syndrome or the presence of meconium below the vocal cords. CONCLUSIONS: We concluded that "early" oronasopharyngeal DeLee suctioning at the perineum does not affect the rate of meconium aspiration syndrome. We speculate that meconium aspiration syndrome is predominantly an intrauterine event associated with fetal distress and that meconium in the airways is merely a "marker" of previous fetal hypoxia. PMID- 1442973 TI - Assessment of the renal circulation during pregnancy with color Doppler ultrasonography. AB - OBJECTIVES: A non-invasive method of assessing the renal vasculature during pregnancy would be useful in the management of patients with renal dysfunction resulting from preeclampsia or chronic renal disease. The objectives of this study were to determine (1) whether color ultrasonography during pregnancy facilitates Doppler interrogation of renal and intrarenal arteries, allowing (2) the assessment of differences between waveforms from nonpregnant and pregnant women and (3) the analysis of waveform variability throughout the kidney and between the right and left kidneys. STUDY DESIGN: In a cross-sectional study renal and intrarenal artery flow waveforms were obtained from women in early (12 to 19 weeks; n = 8), mid (20 to 29 weeks; n = 11), and late (30 to 37 weeks; n = 14) pregnancy with eight age-matched, nonpregnant women acting as controls. Waveforms were analyzed for pulsatility index, resistive index, and systolic/diastolic ratio. RESULTS: Left or right renal and upper- and lower-pole interlobar artery waveforms were obtained from all women. The mean pulsatility index values for the nonpregnant women were not significantly different from those women in early, mid, or late pregnancy. In the nonpregnant women, the left renal artery pulsatility index (1.13 +/- 0.13) was greater than the left lower interlobular artery pulsatility index (0.91 +/- 0.08; p < 0.05). During pregnancy renal and interlobar artery pulsatility index values were greater than those for the corresponding interlobular arteries, but the differences were not significant. Mean renal and intrarenal artery pulsatility index values were greater on the right, but the difference was significant only for the lower interlobular artery in midpregnancy. CONCLUSIONS: Pregnancy does not significantly affect renal and intrarenal artery flow waveforms, nor are there significant differences between waveforms from the renal and interlobar arteries. PMID- 1442974 TI - Changes in coagulation and anticoagulation in women taking low-dose triphasic oral contraceptives: a controlled comparative 12-month clinical trial. AB - OBJECTIVE: The effects of two triphasic oral contraceptives on coagulation and anticoagulation factors were compared in a 12-month open-label study. STUDY DESIGN: Fifty-two women (mean age 26 years) were enrolled in and completed the study; 20 had been randomly assigned to receive levonorgestrel plus ethinyl estradiol, 24 had been randomly assigned to receive norethindrone plus ethinyl estradiol, and eight surgically sterile women acted as untreated controls. Coagulation and anticoagulation factors were measured at baseline and during the sixth and twelfth months. RESULTS: Both oral contraceptives produced significant decreases from baseline in prothrombin time and partial thromboplastin time; there were also significant changes in laboratory control times. Factor XII was significantly increased in both oral contraceptive groups after 6 and 12 months. Fibrinogen antigen was significantly increased for norethindrone plus ethinyl estradiol after 6 and 12 months and for levonorgestrel plus ethinyl estradiol after 12 months. Platelet counts were unchanged. There was a significant increase in antithrombin III activity with norethindrone plus ethinyl estradiol at 12 months. Antithrombin III antigen was unchanged with the oral contraceptives; however, significant increases existed for alpha 1-antitrypsin antigen and plasminogen antigen and activity after 6 and 12 months and for alpha 2 macroglobulin antigen after 12 months for both oral contraceptives. alpha 2 Antiplasmin antigen was significantly increased for norethindrone plus ethinyl estradiol at the 12-month evaluation. There were no significant differences between the oral contraceptives for any coagulation or anticoagulation factor, and mean values generally remained within reference ranges. CONCLUSIONS: Levonorgestrel plus ethinyl estradiol and norethindrone plus ethinyl estradiol had equivalent, minimal effects on hemostasis, and changes in coagulation factors appeared to be balanced by changes in anticoagulation factors. PMID- 1442975 TI - Sleep quality in preeclampsia. AB - OBJECTIVE: Our goal was to study the sleep quality in women with preeclampsia with a special reference to nocturnal body movement activity. STUDY DESIGN: Sleep quality was evaluated in nine women with preeclampsia and eight women with normal term pregnancy by means of questionnaires and by recording the nocturnal body movement activity with the static charge-sensitive bed. RESULTS: Subjective sleep complaints were similar in both groups. The total movement time and the total frequency of body movements in bed were, however, significantly increased in the preeclamptic group. CONCLUSION: The study suggests that sleep is impaired in preeclamptic subjects. PMID- 1442976 TI - Reversal of fetal distress by emergency in utero decompression of hydrothorax. AB - OBJECTIVE: The purpose of our study was to determine whether in utero pleural decompression can improve abnormal cardiotocograms resulting from compressive fetal hydrothorax. STUDY DESIGN: We reviewed all cases of fetal hydrothorax referred to our level 3 fetal medicine unit. Highly pathologic cardiotocographic findings were observed in four third-trimester patients. All had mediastinal compression that resulted in skin edema on the upper part of the body. Prenatal therapy was performed on an emergency basis, two with thoracocentesis and two with pleuroamniotic catheters. RESULTS: One patient went into intractable bradycardia on arrival in the department and died in spite of immediate thoracocentesis. The other three recovered, with normal heart rate patterns after pleural decompression. CONCLUSION: Emergency prenatal therapy may reverse fetal distress in utero, allowing time for delivery of uncompromised infants if possible after a complete evaluation of nonimmune hydrops. PMID- 1442977 TI - Serum collagenase levels in relation to the state of the human cervix during pregnancy and labor. AB - OBJECTIVE: The purpose of our study was to investigate the role of collagenase in the cervical ripening and dilatation process in term pregnancy. STUDY DESIGN: Serum samples were obtained from nonpregnant women (n = 5) and term-pregnant women. The term-pregnant women were either admitted for elective cesarean section or labor induction (unfavorable cervix, n = 19; favorable cervix, n = 12) or in spontaneous, active labor (stiff and inelastic cervix, n = 7; soft compliant cervix, n = 8). Statistical analysis was performed with the Student t test. RESULTS: The nonpregnant women had low serum collagenase levels (5.2 +/- 0.7 micrograms collagen digested per minute per 100 ml serum, mean +/- SEM). At term but before labor, women with unripe cervices had higher collagenase levels (10.3 +/- 0.9). The women with ripe cervices had even higher serum collagenase levels (22.9 +/- 4.2; p < 0.001). During labor, women with stiff and inelastic cervices had lower serum collagenase levels compared with women with soft and compliant cervices (12.9 +/- 1.7 vs 28.0 +/- 4.2; p < 0.01). CONCLUSION: Serum collagenase during ripening at term and in active labor increases, supporting its active role in the ripening process. PMID- 1442978 TI - Genetic offspring in patients with vaginal agenesis: specific medical and legal issues. AB - OBJECTIVE: There are new options for genetic offspring in patients with vaginal agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome). The reported world experience to date with genetic offspring of patients with vaginal agenesis consists of five pregnancies (including two reported here and two frozen embryos). The specifics of these cases are presented for discussion. STUDY DESIGN: We present a retrospective description of two women with vaginal agenesis and their matched gestational carriers with positive outcome of two live births. Care was delivered in a private in vitro fertilization and gamete intrafallopian transfer program. RESULTS: In vitro fertilization of oocytes gathered from the genetic mother with vaginal agenesis and sperm from the genetic father were transferred to a gestational carrier. Two live births and one blighted ovum pregnancy resulted. CONCLUSION: Until recently, treatment for patients with vaginal agenesis (Mayer Rokitansky-Kuster-Hauser syndrome) has centered on the creation of a functional vagina. The technology of in vitro fertilization and embryo transfer, allowing for collection of oocytes from the genetic mother, fertilization by the genetic father, and placement into a gestational carrier, enables a woman without a uterus to have her own genetic children. The specific medical and legal issues involved in facilitating genetic offspring in these instances must be considered; these include the initial matching of the genetic parents with the gestational carrier, cycle synchronization for in vitro fertilization and embryo transfer, anatomic difficulties of oocyte retrieval, birth certificate documentation, and the current legal status of a gestational carrier. PMID- 1442979 TI - Fetal plasma erythropoietin concentration in red blood cell-isoimmunized pregnancies. AB - OBJECTIVE: The aim of this study was to investigate the relationship between fetal anemia, plasma erythropoietin concentration, and erythroblastosis in red blood cell-isoimmunized pregnancies. STUDY DESIGN: Fetal plasma erythropoietin concentration in umbilical venous blood samples from 68 red blood cell isoimmunized pregnancies at 18 to 35 weeks' gestation was measured. Measurements were compared with the appropriate reference range with gestation, and associations with blood pH, erythroblast count, and hemoglobin concentration were examined. RESULTS: The mean fetal plasma erythropoietin concentration and erythroblast count in red blood cell-isoimmunized pregnancies were significantly increased only in severe fetal anemia (hemoglobin deficit > 7 gm/dl). Furthermore, some severely anemic fetuses were hydropic and acidemic. The degree of increase in plasma erythropoietin was significantly associated with both fetal acidemia and, more strongly, fetal erythroblastosis. CONCLUSION: These findings suggest that in fetuses from red blood cell-isoimmunized pregnancies the ability to prevent tissue hypoxia is present until anemia becomes severe, presumably by an increase in cardiac output and tissue perfusion. In severe anemia tissue hypoxia occurs, and the data indicate that fetuses respond by increasing erythropoietin production from at least 20 weeks' gestation. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH. PMID- 1442980 TI - Doppler velocimetry and fetal heart rate studies in nephropathic diabetics. AB - OBJECTIVES: Our objectives were to determine in pregnancies complicated by diabetic nephropathy (1) if impedance to flow in the uterine and umbilical arteries is normal and (2) if these fetuses are hypoxemic and acidemic and if they have decreased fetal heart rate variation and Doppler blood flow redistribution. STUDY DESIGN: In a cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London, serial assessment of fetal heart rate variation and Doppler velocimetry of the placental and fetal circulations was undertaken in six pregnancies complicated by diabetic nephropathy. In all cases cordocentesis was performed within 24 hours before delivery for the measurement of umbilical venous blood gases. RESULTS: Cordocentesis demonstrated these fetuses to be hypoxemic and acidemic. The fetal heart rate variation was decreased; however, impedance to flow in the uterine artery was normal, and increased impedance to flow in the umbilical artery with evidence of blood flow redistribution was observed in only one case. CONCLUSIONS: Fetal hypoxemia and acidemia in pregnancies complicated by diabetic nephropathy is not a consequence of impaired placental perfusion, and the degree of metabolic derangement may be obscured by the apparent normal growth and failure of these fetuses to demonstrate blood flow redistribution. PMID- 1442981 TI - Renal pyelectasis in pregnancy: correlative evaluation of fetal and maternal collecting systems. AB - OBJECTIVE: The current study is aimed at assessing the possibility of a statistical relationship between fetal and maternal collecting system dilatation during pregnancy. STUDY DESIGN: Two hundred thirty consecutive pregnant women and their fetuses (20 to 40 weeks' gestation) were simultaneously examined by ultrasonography. The renal collecting systems were measured, and the frequency of dilatation was subjected to chi 2 analysis. The temporal incidence of fetal pyelectasis was compared with the maternal incidence. RESULTS: Dilatation of maternal collecting systems was detected in 91 of 230 patients (40%) and fetal pyelectasis occurred in 60 of 230 (26%). Fetal pyelectasis was 5.6 times more likely to occur in fetuses of mothers with dilated collecting systems. Furthermore, the temporal incidence of fetal pyelectasis throughout pregnancy appeared similar to that of maternal pyelectasis. CONCLUSION: This study points out the existence of a statistically significant association between maternal and fetal collecting system dilatation during pregnancy. PMID- 1442982 TI - Primary ovarian pregnancy successfully treated with methotrexate. PMID- 1442983 TI - Umbilical venous pressure in nonimmune hydrops fetalis: correlation with cardiac size. AB - OBJECTIVES: Our objectives were to examine the relationship between umbilical venous pressure and cardiac size in nonimmune hydrops fetalis and to assess the role of cardiac failure in the pathogenesis of the disease. STUDY DESIGN: Fourteen fetuses with nonimmune hydrops fetalis were investigated in a tertiary referral unit with high-resolution ultrasonography, echocardiography, and fetal blood sampling. Fetal heart size was assessed by measurement of the cardiothoracic ratio. Umbilical venous pressure was measured at the time of fetal blood sampling with a fluid-filled system. RESULTS: The 10 fetuses with elevated umbilical venous pressures had significantly increased cardiothoracic ratios (p = 0.02). These fetuses also had ascites. Four other fetuses had normal-sized hearts, normal umbilical venous pressures, and no ascites. There was a linear relationship between cardiothoracic ratio and umbilical venous pressure (r = 0.75, p = 0.003). CONCLUSION: Measurement of umbilical venous pressure validates cardiothoracic ratio as a noninvasive assessment of cardiac function in nonimmune hydrops. PMID- 1442984 TI - Monitoring of intravascular fetal transfusions with Doppler velocimetry. AB - Intravascular fetal transfusions are occasionally complicated by extravascular deposition of transfused blood or by fetal bradycardia on penetration of the needle into the umbilical cord. It is desirable therefore to continuously monitor the intravascular location of the needle and the fetal heart rate. This can be achieved by Doppler velocimetry of the umbilical vein and artery during the procedure. The technique is easily performed, does not require moving of the ultrasonography transducer, and appears to be time efficient. PMID- 1442985 TI - Reproductive, menstrual, and medical risk factors for endometrial cancer: results from a case-control study. AB - OBJECTIVE: Our objective was to evaluate the risk for endometrial cancer in relation to reproductive, menstrual, and medical factors. STUDY DESIGN: A case control study of 405 endometrial cancer cases and 297 population controls in five areas of the United States enabled risk to be evaluated. RESULTS: A major risk factor was the absence of a prior pregnancy (relative risk 2.8, 95% confidence interval 1.7 to 4.6). The protective effect of pregnancy appeared to reflect the influence of term births, because spontaneous and induced abortions were unrelated to risk. Among nulliparous women infertility was a significant risk factor, with women having sought medical advice having nearly eight times the risk of those without difficulty conceiving. After adjustment for other reproductive characteristics, age at first birth and duration of breast-feeding were not related to risk. CONCLUSIONS: Elevated risks were found for subjects reporting early ages at menarche (relative risk 2.4 for ages < 12 vs > or = 15) and longer days of flow (relative risk 1.9 for > or = 7 vs < 4 days), but there was no relationship with late ages at natural menopause. Height was not associated with risk, but there was a significant relation to weight, with the risk for 200 versus < 125 pounds being 7.2 (95% confidence interval 3.9 to 13.3). After adjustment for weight and other factors, histories of hypertension and gallbladder disease were not significantly related to risk, but an effect of diabetes persisted (relative risk 2.0, 95% confidence interval 1.1 to 3.6). Hirsutism developing at older ages was also significantly related (relative risk 2.0, 95% confidence interval 1.2 to 3.4). PMID- 1442986 TI - Randomized trial of human versus animal species insulin in diabetic pregnant women: improved glycemic control, not fewer antibodies to insulin, influences birth weight. AB - OBJECTIVE: Macrosomia occurs in infants of diabetic mothers in spite of "nearly normal maternal blood glucose levels" with insulin treatment. Insulin antibodies may carry bound insulin into the fetal blood and thus may be associated with fetal hyperinsulinemia and macrosomia in these infants. Our objective was to test the hypothesis that human insulin is associated with lower insulin antibody levels and less macrosomia than is animal species insulin. STUDY DESIGN: Forty three insulin-requiring pregnant (< 20 weeks' gestation) women, previously treated with animal insulin, were randomized to human and animal insulins and studied at weeks 10 through 20, 24, 28, 32, 36, and 38, at delivery, and at 3 months post partum. Infant blood was drawn at delivery (cord) and at 1 day and 3 months post partum 1 hour after a glucose-amino acid challenge. RESULTS: Women receiving human insulin required significantly less insulin per kilogram of body weight and showed significant dampening of glucose excursions (p < 0.05 for each comparison). Infants born to mothers receiving human insulin weighed 2880 +/- 877 gm compared with 3340 +/- 598 gm for infants of women treated with animal insulin (p < 0.05). There was no difference in insulin antibody levels between groups for either mothers or infants. Infants born to mothers receiving human insulin had a 1 hour C-peptide level after the glucose-amino acid challenge at 3 months of age of 0.21 +/- 0.13 pmol/ml compared with 0.32 +/- 0.13 pmol/ml (p = 0.01). CONCLUSION: Administration of human insulin to pregnant diabetic women has a therapeutic advantage over animal insulin, with less maternal hyperglycemia or hypoglycemia, fewer larger-for-gestational-age infants, and less neonatal hyperinsulinemia. Our data do not support the hypothesis that maternal antibodies to insulin influence infant birth weight. PMID- 1442987 TI - Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: correlations with stage and other clinicopathologic features. AB - OBJECTIVE: This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. STUDY DESIGN: One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay and immunohistochemical analysis were used. The immunohistochemical analysis receptor content was estimated semiquantitatively by a total and a cancer immunohistochemical histologic score. Multiple regression analysis was used in testing independence of established correlations. RESULTS: Estrogen and progesterone receptor dextran coated charcoal values and immunohistochemical histologic scores correlated inversely (p < 0.001) with International Federation of Gynecology and Obstetrics grade of tumor. An inverse correlation (p < 0.0001) between clinical stage and dextran-coated charcoal values was independent of International Federation of Gynecology and Obstetrics grade. Age of patient, years since menopause, and previous estrogen treatment were not related to receptor content. In adenomatous hyperplasia high progesterone receptor levels were seen. CONCLUSION: The inverse correlation between clinical stage of endometrial carcinoma and content of estrogen and progesterone receptors may reflect tumor biologic behavior. PMID- 1442988 TI - Effect of fat and fat-free mass deposition during pregnancy on birth weight. AB - OBJECTIVES: The purposes of our study were to describe the patterns and location of fat and fat-free mass deposition during pregnancy and to evaluate their effects on fetal growth. STUDY DESIGN: Our study is a prospective follow-up of 105 healthy pregnant women who were delivered of term infants. Body composition was evaluated eight times during gestation with anthropometric measures and bioimpedance techniques. Body fat and fat-free mass were calculated with equations specifically developed for this population. RESULTS: Total weight gain was 10.0 +/- 3.5 kg; net weight gain was 3.7 +/- 0.31 kg; birth weight was 3211 +/- 467 gm (values are mean +/- SEM). In these women fat was deposited mostly in the thigh and subscapular region for a total of 6.23 +/- 0.19 kg at term. The period of pregnancy of the largest maternal fat deposition per week is between the twentieth and thirtieth weeks. After adjusting by prepregnancy weight, birth weight is associated with maternal changes in thigh skin folds and fat gain before the thirtieth week of gestation. Infants born to mothers with low fat gain before the thirtieth week were 204 gm lighter than infants born to mothers with fat gain > or = 25th percentile of this population. CONCLUSION: Maternal nutritional status at the beginning of gestation and the rate of fat gain early in pregnancy are the two nutritional indicators most strongly associated with fetal growth in this population. PMID- 1442989 TI - Maternal ventricular tachycardia associated with hypomagnesemia. AB - We present a rare case of recurrent sustained maternal ventricular tachycardia associated with hypomagnesemia. The frequency of this arrhythmia was markedly reduced with magnesium sulfate therapy. Both maternal and fetal outcomes were good. To the best of our knowledge this is the first description of maternal ventricular tachycardia that was associated with hypomagnesemia and did not require treatment with conventional antiarrhythmic medications. We discuss the possible underlying pathophysiologic causes of this condition. PMID- 1442991 TI - The effect of placental management at cesarean delivery on operative blood loss. AB - OBJECTIVES: The effect of alternative methods of placental delivery at cesarean section on blood loss has not been reported. The hypothesis of this study was that spontaneous expulsion of the placenta would reduce operative blood loss, compared with that of manual extraction during cesarean delivery. STUDY DESIGN: We prospectively randomized and compared outcomes of 62 gravid women with manual (n = 31) or spontaneous (n = 31) placental delivery at cesarean section. Operative blood loss was measured directly. RESULTS: Blood loss measured at cesarean delivery was greater in the manually delivered group (967 +/- 248 ml) than in the spontaneously delivered group (666 +/- 271 ml, p < 0.0001). The incidence of postpartum endometritis was sevenfold greater in the manual than the spontaneous group (23% vs 3%, respectively; p < 0.05). CONCLUSIONS: We conclude that spontaneous expulsion of the placenta at cesarean delivery results in less operative blood loss and a lower incidence of postoperative endometritis. PMID- 1442990 TI - Maternal floor infarction: relationship to X cells, major basic protein, and adverse perinatal outcome. AB - OBJECTIVE: Maternal floor infarction of the placenta is characterized by gross placental abnormalities and histologic evidence of X-cell proliferation. Previously, pregnancy-associated major basic protein has been localized to the placental X cell and identified at elevated levels in serum and amniotic fluid in all normal pregnancies. Here we test the hypothesis that pregnancy-associated major basic protein is localized to the X cells in maternal floor infarction and that it contributes to the pathophysiologic features of pregnancies complicated by maternal floor infarction. STUDY DESIGN: Seven patients with eight pregnancies complicated by maternal floor infarction were evaluated. We analyzed placental tissue, serum, amniotic fluid, and placental cyst fluid for pregnancy-associated major basic protein. RESULTS: Placental tissue from pregnancies complicated by maternal floor infarction had increased numbers of X cells and fibrinoid material that occupied or surrounded degenerating villi and that stained intensely for pregnancy-associated major basic protein. Serum pregnancy-associated major basic protein levels were variable and likely cannot be used to predict the occurrence of maternal floor infarction. CONCLUSION: Pregnancy-associated major basic protein, a potent cytotoxin, is localized to X cells and is deposited in close proximity to chorionic villi in maternal floor infarction and may contribute to the pathophysiology of this disorder. PMID- 1442992 TI - Depot leuprolide versus danazol in treatment of women with symptomatic endometriosis. I. Efficacy results. AB - OBJECTIVE: We aimed to assess the efficacy of depot leuprolide versus danazol in the treatment of endometriosis. STUDY DESIGN: A double-blind randomized trial of 270 patients from 22 centers compared the pretreatment and posttreatment laparoscopic extent of endometriosis. Pretreatment and posttreatment endometriosis symptoms and signs were assessed with standardized methods. RESULTS: When compared with danazol, leuprolide depot caused a more rapid and profound suppression of estradiol. Leuprolide depot and danazol were similarly efficacious in decreasing the extent of endometriosis, as well as the pain and tenderness associated with endometriosis. CONCLUSION: Depot leuprolide is an effective alternative to danazol in decreasing the extent of endometriosis and endometriosis-related pain. PMID- 1442994 TI - The effect of the menstrual cycle on serum CA 125 levels: a population study. AB - OBJECTIVE: Our objective was to assess the effect of the menstrual cycle on CA 125 levels in a population study. STUDY DESIGN: Serum CA 125 was measured in 1478 women, with day of menstrual cycle noted in 574 women. Repeat examination was performed in women with elevated results, and 40 of these women were tracked by weekly examination of CA 125 levels. RESULTS: A significant difference was demonstrated when midcycle samples were compared with day 1 and day 28 samples (p < 0.05). In spite of this significance the difference was not clinically useful. Elevated serum CA 125 (> 35 U/ml) levels were present in 77 (5.2%) of the premenopausal women. A significant variation was demonstrable with higher CA 125 levels about the time of menstruation in 29 of the 40 women tracked. CONCLUSION: This study suggests that in the population as a whole the effect of the menstrual cycle on serum CA 125 is not clinically significant, but single elevated levels in an individual may represent menstrual fluctuation. PMID- 1442993 TI - Glycated hemoglobin of fractionated erythrocytes, glycated albumin, and plasma fructosamine during pregnancy. AB - OBJECTIVE: To evaluate glucose metabolism during pregnancy, we measured plasma fructosamine, glycated albumin, and the stable glycated hemoglobin of the light and dense erythrocytes. STUDY DESIGN: The abnormal glucose tolerance group comprised patients with gestational diabetes and those with one abnormal value on a 75 gm oral glucose tolerance test. Erythrocyte fractionation was performed by capillary centrifugation. RESULTS: In normal pregnancy glycated hemoglobin of the light erythrocytes was reduced in the second and third trimesters (3.42% +/- 0.62% [mean +/- SD] [n = 306] in the first trimester, 2.15% +/- 0.48% [n = 353] in the second, and 2.06% +/- 0.58% [n = 300] in the third), and dense erythrocytes were higher in the third trimester (first 4.59% +/- 0.46%, second 4.70% +/- 0.49%, third 5.29% +/- 0.73%). Glycated albumin and fructosamine followed a pattern similar to the light erythrocytes. The group with abnormal glucose tolerance had significantly higher levels of glycated hemoglobin of the light erythrocytes in the first and third trimesters and glycated hemoglobin of the dense erythrocytes and glycated albumin in all trimesters. CONCLUSION: The biphasic change in nonfractionated glycated hemoglobin is the sum of the lower glycated hemoglobin of the light erythrocytes and the higher glycated hemoglobin of the dense erythrocytes in late pregnancy. The stable glycated hemoglobin of fractionated erythrocytes and the glycated albumin accurately reflect maternal glucose metabolism during pregnancy. PMID- 1442995 TI - The fetal recoil test. AB - A reassuring fetal recoil test has positive and negative predictive values of 98% and 8%, respectively, for a reactive nonstress test (sensitivity 89%, specificity 33%). Among 21 of 30 subjects in whom recoil was present immediately before delivery, none had umbilical arterial pH values < or = 7.20 versus 5 of 9 (56%) with nonreassuring recoil (p = 0.005). We concluded that a reassuring fetal recoil test is a reliable marker for fetal well-being. PMID- 1442996 TI - Recurrent squamous carcinoma of the vulva. AB - OBJECTIVE: This study reviews experience at Indiana University with recurrent squamous carcinoma of the vulva over an 18-year period from 1971 to 1989. The pattern of recurrence, time interval to recurrence, and efficacy of salvage therapy are evaluated in the context of the primary tumor. STUDY DESIGN: This is a retrospective study of 40 patients, 21 of whom underwent primary therapy for invasive squamous carcinoma of the vulva at Indiana University. RESULTS: Vulvar recurrences were observed in 17 patients (43%), the groin was involved in 12 (30%), whereas pelvic and distant recurrences were observed in 2 (5%) and 9 (22.5%) patients, respectively. Salvage surgery and/or radiotherapy were successful in 25 patients (62.5%) alive from 1 to 144 months (median 8 months) from secondary therapy. Survival after retreatment varied significantly by site of recurrence (p = 0.002), tumor grade (p = 0.009), and interval to recurrence (p < 0.001). Best outcomes were in patients with initial stage I or II disease (International Federation of Gynecology and Obstetrics), grade 1 tumors, local failure, and interval to relapse of > 16 months' duration. Two of 12 patients with groin recurrences were salvaged with surgery and radiotherapy. CONCLUSION: Long-term follow-up of patients with vulvar cancer and careful restaging at the time of recurrence are mandatory. Although local and nodal recurrences may be controlled with surgery and/or radiotherapy, regional recurrences are usually fatal. PMID- 1442997 TI - Contraction monitoring with a manager calculator. AB - A simple manager calculator was used as a contraction monitor, and external parallel registrations were performed on 10 pregnant women in labor with the Psion and other kinds of tocodynamometers. A 94% correlation was found between the simultaneously registered data. PMID- 1442998 TI - Mechanisms of relaxation induced by prostaglandins in isolated canine uterine arteries. AB - OBJECTIVE: Prostaglandins liberated from the uterus in response to chemical and physical stimuli would be important modulators of uterine arterial tone and blood flow. This study was aimed at analyzing mechanisms of vasodilator action of prostaglandins in uterine arteries. STUDY DESIGN: Canine uterine artery strips were suspended in Ringer-Locke solutions for isometric tension recording. RESULTS: Prostaglandin F2 alpha-induced relaxation was reversed to contraction by cyclooxygenase inhibitors and suppressed by tranylcypromine (prostaglandin I2 synthesis inhibitor) or diphloretin phosphate (an inhibitor of prostaglandin F2 alpha and prostaglandin I2 actions) but was unaffected by endothelium denudation. Prostaglandin E2-induced relaxation was not attenuated by indomethacin but was partially inhibited by a nitric oxide synthase inhibitor and endothelium denudation. Relaxation induced by beraprost (prostaglandin I2 analog) was suppressed by diphloretin phosphate but was not influenced by indomethacin and endothelium denudation. CONCLUSION: It appears that prostaglandin F2 alpha induced relaxation is mediated by prostaglandin I2 released from subendothelial tissues, whereas prostaglandin E2-induced relaxation is caused by release of endothelium-derived nitric oxide and also by an endothelium-independent mechanism. PMID- 1442999 TI - Chemotactic factor in the pregnant rabbit uterine cervix. AB - OBJECTIVE: Neutrophil accumulation is one of the characteristic changes observed in uterine cervical stroma at term pregnancy, but chemotactic activity in the tissue is obscure. Our study examined the existence and production of chemotactic factor in the rabbit uterine cervix. STUDY DESIGN: Uterine cervical explants of rabbits at term pregnancy and nonpregnant rabbits were cultured with and without interleukin-1 alpha. Rat neutrophilic chemotaxis in culture media was evaluated with a Boyden chamber. RESULTS: Tissue extract from the pregnant rabbit uterine cervix at term pregnancy contained more chemoattractive activity than the nonpregnant cervix. Production of chemoattractant from cultured rabbit cervical explants at term pregnancy was also higher than that from nonpregnant explants. The addition of interleukin-1 alpha to the culture system promoted its production. This chemoattractant was characterized as a true chemotactic factor and heat-stable and trypsin-sensitive protein with an apparent relative molecular mass of 16,200. So far, these properties are very similar to those of the interleukin-8 family. Rabbit uterine cervical fibroblast is characterized as a chemotactic factor-producing cell in the rabbit uterine cervix. CONCLUSION: These results indicate that interleukin-8-like chemotactic factor participates in the cervical ripening at term pregnancy and that the production of this factor is controlled effectively by interleukin-1. PMID- 1443000 TI - Transient umbilical cord occlusion causes hippocampal damage in the fetal sheep. AB - OBJECTIVE: The purpose of our study was to examine the neuronal outcome after a standardized period of umbilical cord occlusion. STUDY DESIGN: The umbilical cord was clamped for 10 minutes in nine experimental and four control chronically instrumented fetal sheep. Three days later the animals were killed for histologic interpretation. Systemic, electrophysiologic, and neurohistologic effects were compared by analysis of variance. RESULTS: Clamping of the cord resulted in transient severe asphyxia, hypotension (24 +/- 5 mm Hg, p < 0.01), bradycardia (72 +/- 14 beats/min, p < 0.001), depressed electroencephalographic activity (-17 +/- 2 dB, p < 0.001), and an increase in cortical impedance. The electroencephalographic activity was depressed for 5 +/- 2 hours in spite of rapid recovery of arterial oxygen content. Neuronal loss was found in the hippocampus. Neither epileptiform electroencephalographic activity nor infarction were observed. Three animals with poor blood gas levels died during the occlusion. CONCLUSION: An isolated and brief period of umbilical cord occlusion in utero can cause predominantly hippocampal damage without persistent functional changes in cortical activity and with rapid recovery of other potential indicators of fetal asphyxia. PMID- 1443001 TI - Secretion of prolactin and insulin-like growth factor I by decidual explant cultures from pregnancies complicated by intrauterine growth retardation. AB - OBJECTIVES: Prolactin and insulin-like growth factor I secretion elsewhere in the uterus have been shown to decrease when tissue-specific growth is limited. We investigated their secretion by decidual explant cultures from pregnancies complicated by fetal intrauterine growth retardation. STUDY DESIGN: Explant cultures from 13 pregnancies complicated by intrauterine growth retardation and 12 control pregnancies were established in minimal essential medium and media was harvested after 24 hours of culture. Prolactin and insulin-like growth factor I concentrations were determined by radioimmunoassay. Total protein in the media was also measured. Data were analyzed by analyses of variance and linear regression. RESULTS: Decidual prolactin secretion in the pregnancies with intrauterine growth retardation was reduced to 109 +/- 31 ng/100 mg tissue per 24 hours compared with 254 +/- 51 ng in the controls (p = 0.01). Insulin-like growth factor I secretion was reduced to 1.9 +/- 0.6 ng/100 mg tissue per 24 hours from 7.1 +/- 0.9 ng/100 mg in the controls (p < 0.0001). Total protein secretion did not differ between the two groups. Decidual prolactin and insulin-like growth factor I secretion had a highly significant positive correlation (r = 0.71, p = 0.0001). CONCLUSIONS: Our data show that two protein hormones secreted by the maternal decidua are dramatically reduced in intrauterine growth retardation and warrant further investigation into their roles in the intrauterine environment. PMID- 1443002 TI - Human ovarian surface epithelial cells are capable of physically restructuring extracellular matrix. AB - OBJECTIVE: After ovulation the human ovarian surface epithelium proliferates at the wound edges, migrates over the ovulatory defect, and contributes to its repair primarily by the action of proteolytic enzymes and by the deposition of new matrix material. We examined the potential for human ovarian surface epithelial cells to physically remodel extracellular matrix in culture, similar to collagen gel lattice contraction by fibroblasts, a well-known culture model for wound repair, as an additional role of human ovarian surface epithelium in wound repair. STUDY DESIGN: Human ovarian surface epithelium cells from ovarian biopsies of 11 patients were grown in culture and plated onto a combination of collagen gel and rat ovarian surface epithelial-derived extracellular matrix. The degree of matrix contraction was measured as the percentage of the original culture diameter. RESULTS: Human ovarian surface epithelial cells surrounded and contracted the combination of matrices into a dense matrix organoid. The degree of organoid contraction was related to the number of human ovarian surface epithelial cells plated per organoid and to the inclusion of fibroblasts within the collagen gel but was not affected either by adding epidermal growth factor and hydrocortisone to the culture medium or by reducing the serum component of the medium. CONCLUSION: Human ovarian surface epithelial organoids may be useful for the study of normal and abnormal ovarian events such as ovulatory wound repair and cyst formation. PMID- 1443003 TI - Autonomic and arginine vasopressin modulation of the hypoxia-induced atrial natriuretic factor release in immature and mature ovine fetuses. AB - OBJECTIVE: This study investigated the maturational change in the atrial natriuretic factor response to hypoxia in ovine fetuses and the role of the autonomic nervous system and arginine vasopressin in modulating this response. STUDY DESIGN: Chronically catheterized ovine fetuses from 110 to 135 days' gestation were subjected to 30 minutes of hypoxia. The fetuses were either intact, treated with hexamethonium to block the autonomic nervous system, or treated with a pressor antagonist of arginine vasopressin. RESULTS: Hypoxia elevated plasma atrial natriuretic factor levels by 1635 +/- 265 pg/ml in immature fetuses; this response was greater than the increase of 748 +/- 189 pg/ml in mature fetuses (p < 0.0001). Blockade of the autonomic nervous system reduced the atrial natriuretic factor response and suppressed the vascular pressure changes to hypoxia in immature but not in mature fetuses. A vasopressin pressor antagonist suppressed the atrial natriuretic factor but not vascular pressure responses to hypoxia in mature fetuses. CONCLUSIONS: This study demonstrates that the immature fetus manifested a greater atrial natriuretic factor response to hypoxia than did the mature fetus. This enhanced response appeared to be dependent on the modulatory effects of the autonomic nervous system on vascular pressures during hypoxia. In addition, arginine vasopressin appeared to augment the atrial natriuretic factor response to hypoxia in the mature fetus independent of vascular pressure changes. PMID- 1443004 TI - Acute intrauterine hypoxia increases amniotic fluid prostaglandin F metabolites in the pregnant sheep. AB - OBJECTIVE: Amniotic fluid infection promotes cytokine release, prostaglandin production, and premature labor. In several tissues local hypoxia also activates the secretion of cytokines. Many patients initially seen in premature labor carry small-for-gestational-age fetuses, a condition associated with intrauterine hypoxia. The purpose of our study was to determine whether a reduction in placental blood flow and subsequent acute hypoxia affects prostaglandin secretion by the placenta. STUDY DESIGN: We chronically catheterized six pregnant sheep at 120 days of gestation. We placed catheters in the maternal and fetal femoral arteries and in the amniotic fluid cavity. A flow probe and snare were placed around the common uterine artery. RESULTS: A 30-minute uterine circulation occlusion of 30% of its control value produced an increase in prostaglandin F metabolite from 790 +/- 157 to 944 +/- 184 pg/ml within 10 minutes (p < 0.01). Additional uterine blood flow reduction to 60% of control increased the amniotic fluid prostaglandin F metabolites concentration to 894 +/- 202 (p < 0.05, analysis of variance). No increase in mean intrauterine pressure was detected (p > 0.1). CONCLUSIONS: We speculate that the prostaglandin increase in amniotic fluid in response to intrauterine hypoxia could eventually lead to premature labor. Whether the increase in prostaglandins is mediated by changes in cytokines is unknown at the present time. PMID- 1443005 TI - Changes in pupillary diameter in relation to eye-movement and no-eye-movement periods in the human fetus at term. AB - OBJECTIVE: The aim of our study was to reveal whether pupils dilate and constrict in a time sequence in the human fetus and to assess the relationship between changes in pupillary diameter and eye-movement-no-eye-movement periods. STUDY DESIGN: We simultaneously observed pupil and eye movement with real-time ultrasonography in 30 human fetuses at 36 to 41 weeks' gestation. Eighteen were excluded because of data loss. Statistical analysis of pupillary diameter changes were made on the remaining 12 fetuses with the least median of squares regression. RESULTS: Pupillary diameters were found to be differentiated with statistical significance into two groups: 9.7% for the dilated pupil (median 3.0 mm) and 90.3% for the constricted pupil (1.7 mm). The percentage of dilated pupils during the eye-movement period (14.3%) was significantly greater than that during the no-eye-movement period (2.3%; Wilcoxon rank sum test, p < 0.0001). CONCLUSION: These findings indicate a close relation between pupillary dilatation and eye-movement periods in the human term fetus. PMID- 1443006 TI - Early detection of preeclampsia. PMID- 1443007 TI - Anesthesia for neonatal circumcision aids hazard detection. PMID- 1443008 TI - Preterm versus term asphyxia. PMID- 1443009 TI - What is intercurrent eclampsia? PMID- 1443010 TI - Hemorrhagic endovasculitis of the placenta. PMID- 1443011 TI - A modified freehand ultrasonographically guided technique in transabdominal chorionic villus sampling. PMID- 1443012 TI - Pro-life people oppose violence. PMID- 1443013 TI - Community care of corneal ulcers. AB - Because of increasing concern about the appropriate and cost-effective use of eye care services and procedures, several organizations have sought to arrive at practice guidelines or practice patterns from which physicians can draw guidance. To assess the potential effectiveness of such guidelines, we reviewed the care of patients with corneal ulcers. Corneal specialists recommend that cultures be obtained before initiation of treatment. We determined whether ophthalmologists implemented these guidelines by the following: (1) a review of records of 79 patients referred to a tertiary care corneal and external disease service for evaluation of keratitis, and (2) a survey by mail of practicing ophthalmologists. Antibiotic therapy without any cultures was observed in 38 of 79 referred patients with corneal ulcers (48.1%). Our survey of general ophthalmologists disclosed that 274 of 560 patients with corneal ulcers (48.7%) were treated with antibiotics without any cultures being obtained. Compliance with recommended practice in the care of corneal ulcers is poor, as measured with either method. This procedure provides insights into more effective implementation of future practice guidelines. PMID- 1443014 TI - Lattice degeneration of the retina and the pigment dispersion syndrome. AB - Retinal detachment occurs more frequently in patients with pigment dispersion syndrome. We evaluated the incidence of peripheral retinal abnormalities known to predispose to rhegmatogenous retinal detachment in a consecutive series of 60 patients with pigment dispersion syndrome with or without glaucoma. Lattice degeneration was present in at least one eye of 12 patients (20%). Seven patients had bilateral lesions. Full-thickness retinal breaks were found in seven patients (11.7%) and two patients (3.3%) had asymptomatic rhegmatogenous retinal detachments that required scleral buckle procedures. The incidence of lattice degeneration and full-thickness retinal breaks appears to be increased in this group of patients, and may be responsible for the increased risk of rhegmatogenous detachment. PMID- 1443015 TI - Changes in optic disk characteristics and number of nerve fibers in experimental glaucoma. AB - We compared the change in cup/disk ratio and neuroretinal rim area-to-disk area to estimated change in the number of optic nerve fibers in 12 cynomolgus monkeys with unilateral experimental glaucoma. Changes in the cup/disk ratios and neuroretinal rim area-to-disk area were estimated from stereoscopic optic disk photographs that were obtained before and after the development of increased intraocular pressure. Change in the number of optic nerve fibers in the glaucomatous nerves was estimated by comparing them to their fellow normal nerves. A significant linear correlation was present between change in the cup/disk ratios and neuroretinal rim area-to-disk area, and estimated change in the number of optic nerve fibers (r > or = .85; P < .0002). In optic disks with initial cup/disk ratios of 0.2 to 0.3 and neuroretinal rim area-to-disk area of 0.9, an increase in the cup/disk ratio of 0.1 and a decrease of 0.1 in the neuroretinal rim area-to-disk area is associated with a 10% and 9% loss of optic nerve fibers, respectively. PMID- 1443016 TI - The influence of exposure duration in transscleral Nd:YAG laser cyclophotocoagulation. AB - Transscleral cyclophotocoagulation was performed in human autopsy eyes by using three Nd:YAG lasers with different durations of exposure: a pulsed, contact laser with a duration of 0.75 millisecond and a range of one to ten pulses per burst (GLase 106, Sunrise Technologies, Fremont, California); a pulsed, noncontact laser with a duration of 20 milliseconds (Microruptor 2, Lasag Medical Lasers, Thun, Switzerland); and a continuous-wave, contact laser with durations of 700 and 2,000 milliseconds (Microruptor 3, Lasag Medical Lasers, Thun, Switzerland). Tissue responses were observed with a high-magnification videographic recording technique to analyze the immediate, real-time laser effects, and by light microscopy to characterize the laser-induced lesions further. Videographically, both pulsed lasers were noted to cause mild whitening of the pigment epithelium with frequent vaporization and explosive tissue disintegration. Histologically, the 0.75-millisecond pulse typically produced the most marked epithelial disruption, referred to as an explosive-like lesion, whereas the 20-millisecond pulse more often caused moderate tissue disruption with elevation of the epithelial layers in a blister-like lesion. In contrast, the continuous-wave laser was observed videographically to produce prominent tissue whitening and puckering, seen histologically as convolution of the epithelium and coagulation of stroma, which was called a shrinkage-like lesion. Our study suggests that exposure duration influences in vitro tissue response to transscleral Nd:YAG cyclophotocoagulation, although in vivo studies and clinical trials are needed to determine which tissue response is optimum for clinical use. PMID- 1443017 TI - Acquired oculomotor, trochlear, and abducent cranial nerve palsies in pediatric patients. AB - Between January 1966 and December 1988, 160 pediatric patients (age range, 0 to 17 years) were seen at the Mayo Clinic with an acquired oculomotor (35 patients), trochlear (19 patients), abducent (88 patients), or multiple (18 patients) cranial nerve palsy. The clinical findings in the 160 pediatric patients were compared with the results obtained in other reviews of cranial nerve palsies in the pediatric age group and with the adult Mayo Clinic patients with acquired cranial nerve palsies. Trauma was the most common reason for an acquired cranial nerve palsy in our pediatric group. The percentage of patients with an acquired cranial nerve palsy resulting from trauma was significantly greater in the pediatric group (42.5%) than in adults (15.4%) (P < .01). The difference between the percentage of adults (15.2%) and pediatric patients (16.9%) with a cranial nerve palsy secondary to a neoplasm was not statistically significant (P = .28). PMID- 1443018 TI - Development of object vision in infants with permanent cortical visual impairment. AB - We examined 30 infants in whom cortical visual impairment was diagnosed during their first year of life to ascertain prognostic factors for the development of object vision, defined as the ability to recognize faces or hand-held toys. All patients were followed up for a minimum of 12 months. The most common causes of cortical visual impairment in the 30 infants were hydrocephalus in nine infants (30.0%), birth asphyxia or neonatal hypoxia in eight infants (26.7%), intracranial hemorrhage with or without hydrocephalus in seven infants (23.3%), and meningitis in five infants (16.7%). Lack of development of object vision was associated only with hypoxia (P = .013). Findings on ophthalmic examination, an abnormality in the visual pathway on computed tomographic or magnetic resonance scan, and seizures, hydrocephalus, intracranial hemorrhage, meningitis, cerebral palsy, developmental delay, prematurity, microcephaly, and hearing deficit, did not appear to be risk factors for the lack of development of object vision. PMID- 1443019 TI - Ocular findings in Cockayne syndrome. AB - The ocular findings in eight patients with Cockayne syndrome included enophthalmos, hyperopia, poor pupillary dilation, and retinal dystrophy in all patients. Four patients had strabismus. Two patients had cataracts. Three patients had nystagmus. Visual acuity was relatively well preserved in six patients, including a 25-year-old man with a visual acuity of 20/60 in each eye despite advanced retinal pigmentary changes. Failure of DNA and RNA synthesis to recover after ultraviolet light exposure as well as selective loss of repair of transcriptionally active DNA may account for the ocular abnormality in this progeric syndrome. PMID- 1443020 TI - Orbital cellulitis caused by Eikenella corrodens. AB - Eikenella corrodens is a gram-negative, facultative anaerobic bacillus with specific culture and growth requirements and unusual antibacterial susceptibilities. It has only recently been recognized as a human pathogen. Ocular and adnexal infections with this organism are rare especially in children. We treated two children with orbital cellulitis caused by E. corrodens. One was an 8-year-old boy; the other was an 11-year-old girl. Orbital cellulitis in both patients occurred after an upper respiratory tract infection. Sinusitis and a subperiosteal abscess were present in both patients. Eikenella corrodens and Streptococcus viridans were isolated from the boy; E. corrodens was the sole isolate in the girl. Intravenous ampicillin, prolonged hospitalization, and surgical drainage of the orbit were required to control the infection in both patients. Eikenella corrodens must be considered in the differential diagnosis of orbital cellulitis in children, and ophthalmologists must become familiar with the characteristics of this peculiar organism. PMID- 1443021 TI - Diode laser photocoagulation for prethreshold, posterior retinopathy of prematurity. AB - Nine infants with posterior retinopathy of prematurity were treated by using the diode laser through an indirect ophthalmoscopic delivery system. Treatment was commenced as soon as plus disease (defined as tortuosity and dilation of posterior vessels) developed. We defined posterior retinopathy of prematurity as retinopathy of prematurity located in zone 1 (the limits of zone 1 are defined as twice the disk-fovea distance in all directions from the optic disk, that is, an arc of 60 degrees centered on the optic disk) or the posterior one half of zone 2 (zone 2 extends from the edge of zone 1 peripherally to a point tangential to the nasal ora serrata and around to an area near the temporal anatomic equator). Disease regressed in all eyes. These results are encouraging and represent an improvement over the results obtained by allowing these eyes to reach threshold (threshold disease is defined as 5 or more contiguous or 8 total clock hours of neovascularization in zone 1 or 2 in the presence of plus disease) before intervention. PMID- 1443022 TI - Posterior segment changes in membranoproliferative glomerulonephritis. AB - Membranoproliferative glomerulonephritis is a renal disorder characterized by proliferation of cells and changes in the basement membrane of the glomerulus. The disease is divided into three subtypes: type I, characterized by the presence of subendothelial electrondense deposits; type II, characterized by deposition of electrondense material of unknown origin in the lamina densa of the glomerular basement membrane; and type III, characterized by lesions having both type I and type II qualities. Specific posterior segment changes have been reported with membranoproliferative glomerulonephritis type II. We examined three patients with membranoproliferative glomerulonephritis type II and two patients with type III disease. All three patients with type II disease had Bruch's membrane and retinal pigment epithelial changes, whereas both patients with type III disease had normal posterior segments. PMID- 1443023 TI - Posterior capsulotomy as a complication of indirect laser photocoagulation. AB - Two pseudophakic patients with posterior chamber intraocular lens implants and intact posterior capsules underwent indirect laser photocoagulation during their immediate postoperative period (24 and 72 hours postoperatively, respectively). Laser treatment was indicated for a retinal break noted after vitrectomy and scleral buckling in one patient and after peribulbar perforation during cataract extraction in the other patient. Ocular media were hazy because of vitreous haze and hemorrhage in both eyes and higher power laser settings were required to produce adequate chorioretinal burns during photocoagulation. Inadvertent large posterior capsulotomy as a complication was noted in both eyes. High-power settings and hazy ocular media are risk factors toward this complication. We recommend that slit-lamp examination be performed before, during, and after indirect laser treatment, especially when higher power settings are required. PMID- 1443024 TI - Retained lens fragments after phacoemulsification manifesting as marked intraocular inflammation with hypopyon. AB - We reviewed the medical records of four patients with marked intraocular inflammation and hypopyon as the initial manifestation of retained lens fragments after phacoemulsification. The severe inflammatory reaction occurred between one month and one year after the cataract extraction. All four patients underwent pars plana vitrectomy to remove the lens fragments. The vitreous specimens were cultured to rule out infectious endophthalmitis. In all patients, no organisms were isolated from the vitrectomy specimens placed on both aerobic and anaerobic media. All patients had improved vision and resolution of the marked intraocular inflammation after vitrectomy. Echography was useful in establishing the diagnosis in these uncommon cases. PMID- 1443026 TI - Conjunctival involvement in paraneoplastic pemphigus. AB - Paraneoplastic pemphigus is a recently described autoimmune inflammatory mucocutaneous disease associated with an underlying neoplasm. Although histopathologic and direct immunofluorescence findings of involved skin and mucous membranes are consistent with pemphigus vulgaris, indirect immunofluorescence and immunoprecipitation study results are unique. We treated two patients with non-Hodgkin's lymphoma and paraneoplastic pemphigus. Both patients had bilateral bulbar conjunctival hyperemia and diffuse papillary tarsal conjunctival reactions. One patient had sloughing of conjunctival epithelium and the other had tarsal conjunctival cicatrization and forniceal shortening. Histopathologic findings of conjunctivae obtained from both patients were consistent with pemphigus vulgaris. Diffuse deposition of IgG and C3 in the intercellular substance of the conjunctival epithelium was demonstrated by direct immunofluorescence. Indirect immunofluorescence testing disclosed binding of autoantibodies to rodent bladder and intestinal epithelium. Immunoprecipitation disclosed antibodies reactive to Desmoplakin I (250 kd), bullous pemphigoid (230 kd), Desmoplakin II (210 kd) and 190-kd proteins. Ophthalmologists and pathologists should be aware of the conjunctival changes in paraneoplastic pemphigus. PMID- 1443025 TI - Vogt-Koyanagi-Harada syndrome in patients with Cherokee Indian ancestry. AB - Eight patients with Vogt-Koyanagi-Harada syndrome who have Cherokee Indian ancestry ranged from 17 to 49 years of age. Five of the patients were black, three were white. Visual acuity at the time of initial examination ranged from 20/20 to counting fingers. Clinical findings included granulomatous iridocyclitis in six patients, vitreitis in seven patients, disk edema in five patients, exudative retinal detachment in six patients, and multifocal choroidal lesions in all eight patients. All of the patients were treated with systemic corticosteroids, and they recovered visual acuity of 20/40 or better. The seven patients assayed had the HLA-DRw52 haplotype, including five who were homozygous for this allele. This finding may add to the increasing evidence that a class II HLA antigen at a D-related locus may predispose carriers to the development of Vogt-Koyanagi-Harada syndrome. PMID- 1443027 TI - Optic neuropathy in Hodgkin's disease. AB - Hodgkin's disease is a rare cause of infiltrative optic neuropathy, which typically evolves late in the disease course. We managed an unusual case of isolated optic neuropathy in a 21-year-old man occurring during clinical remission from Hodgkin's disease. Radiotherapy and treatment with high-dose systemic corticosteroids resulted in dramatic improvement in vision. Even without other evidence of recurrent disease, acute-onset optic neuropathy in a patient with a history of a lymphoproliferative disorder should raise the question of a reemergence of the malignancy. PMID- 1443028 TI - Divergent approaches to the management of corneal ulcers. PMID- 1443029 TI - Ultrastructure of human immunodeficiency virus in corneal epithelial scraping. PMID- 1443030 TI - Propofol and surgical contamination in strabismus surgery. PMID- 1443031 TI - Vertical fusion amplitude in normal adults. PMID- 1443032 TI - Moraxella infection of a scleral buckle. PMID- 1443033 TI - Intraconjunctival cavitary inclusions of silicone oil complicating retinal detachment repair. PMID- 1443034 TI - Conjunctival concretions. PMID- 1443035 TI - Development of a retinal artery macroaneurysm at the site of a previously detected retinal artery embolus. PMID- 1443036 TI - Nonbacterial thrombotic endocarditis and cortical blindness. PMID- 1443037 TI - Visual recovery after radiation therapy of orbital lymphoma. PMID- 1443038 TI - Successful therapy for trilateral retinoblastoma. PMID- 1443039 TI - Successful therapy for trilateral retinoblastoma. PMID- 1443040 TI - Multifunction endolaser probe. PMID- 1443041 TI - Pulmonary vascular amyloidosis in aged dogs. A new form of spontaneously occurring amyloidosis derived from apolipoprotein AI. AB - The N-terminus of a mutant form of apolipoprotein AI [apoAI] has previously been shown to be the subunit protein of amyloid fibrils in a human kindred with a form of familial amyloid polyneuropathy (FAP, type III) and in a recently reported kindred with a form of non-neuropathic hereditary amyloidosis. In this study, we demonstrate by amino-acid sequence analysis, that a form of vascular amyloidosis occurring in the lungs of aged dogs is derived from a N-terminal fragment of apoAI and that no amino acid substitution is present in this confirmed sequence. This represents the first documentation of apoAI as a precursor for a form of amyloidosis in animals, and provides the first documentation of apoAI as a precursor for amyloid fibrils in a form of age-associated ("senile") amyloidosis. Secondary structure prediction analysis of the N-terminal regions of normal human and dog apoAI indicated a propensity for beta-pleated sheet conformation, and thus amyloidogenesis, in 40 and 45% of the respective sequences. These results suggest that apoAI (like transthyretin) may serve as an amyloid precursor protein for both familial and senile forms of amyloidosis. ApoAI should, therefore, be considered as a potential amyloid precursor when forms of human senile amyloidosis of unknown origin are evaluated. PMID- 1443042 TI - Interleukin-4 may contribute to the abundant T-cell reaction and paucity of neoplastic B cells in T-cell-rich B-cell lymphomas. AB - T-cell-rich B-cell lymphomas (TCRBCLs) are diffuse lymphomas that contain a minority of large neoplastic B cells amidst a majority of non-neoplastic T cells and numerous histiocytes, an unusually pronounced reactive component not seen in most diffuse large B-cell lymphomas (DLBCLs). This reaction may be influenced by various cytokines secreted by lymphoma or reactive cells; therefore, expression of interleukin (IL)-1 beta, IL-2, IL-4, IL-6, and IL-9 was evaluated immunohistochemically on paraffin-embedded sections of 18 TCRBCLs and was compared with that of 15 DLBCLs containing a minority of reactive T cells and to that of seven reactive lymph nodes. Moderate to intense expression of IL-4 was detected in variable numbers of tumor cells and in numerous histiocytes in 16 TCRBCLs. In contrast, intense IL-4 expression in numerous histiocytes was observed in only one of 15 DLBCLs with few T cells. In four other DLBCLs and three reactive nodes, moderate to intense staining for IL-4 was noted only in rare large transformed cells or in occasional histiocytes. Except for one IL-1 beta positive and another IL-9 positive TCRBCL, there was no marking or weak staining only with other cytokine antibodies in the neoplastic and reactive cases studied. The expression of IL-4 in most TCRBCLs, but not in other DLBCLs or in reactive nodes, suggests that this cytokine is one factor involved in the pathobiology of the abundant T-cell reaction and, perhaps, contributes to the paucity of neoplastic B cells in TCRBCLs. PMID- 1443043 TI - Synaptophysin expression in "ependymal tumors" induced by ethyl-nitrosourea in rats. AB - Synaptophysin expression was studied in seven "ependymomas" induced by transplacental administration of ethyl-nitrosourea in rats. In all the cases, strong positivity for synaptophysin was found on tumor cells. This finding supports previous studies suggesting that ENU-induced brain tumors considered to be ependymal neoplasms, are, in fact, primitive neuroectodermal tumors. PMID- 1443044 TI - The rat testicular artery: a model of spontaneous aneurysmal-like structure formation. AB - The straight spermatic and highly convoluted testicular arteries were studied by light microscopy in adult and aging normotensive (NT) and spontaneously hypertensive (SHR) rats. In younger rats, on the internal part of bends of the testicular artery, areas lacking the media similar to classical cerebral arterial medial defects were observed. At the same location, in other bends, structurally defective areas (SDA) constituted by or including medial defects but also lacking the internal elastic lamina and which in some cases evaginated, were present. Structurally defective areas were less numerous in SHR than in NT rats at 6 months, suggesting that intrinsic differences may exist between rat strains. In contrast, in old rats, the number of SDA was higher in hypertensive than in normotensive rats, supporting the role of hemodynamics in SDA formation. With age, SDA enlarged in both rat strains, and most of them became structurally similar to aneurysms, ie, lacking the internal elastic lamina and medial cells and with a dilated lumen, supporting the view that medial defects are sites of aneurysmal structure development. In hypertensive rats, fibrin and lipid deposits occurred within these aneurysmal-like structures. In the straight part of the spermatic artery no such structural modifications occurred, suggesting that either hemodynamics and/or structural development, both dependent on arterial geometry, are determinant in SDA formation. The results are discussed in view of the use of the rat testicular artery as a possible model of the formation of spontaneous aneurysmal-like structures relevant to cerebral aneurysms. PMID- 1443045 TI - Detection of laminin receptor mRNA in human cancer cell lines and colorectal tissues by in situ hybridization. AB - The 67-kd high-affinity laminin receptor (67 LR) is a gene product whose expression appears to be associated with the invasive and metastatic phenotype of a variety of human cancer cells. Northern blot hybridization has been routinely used to quantify the level of 67 LR mRNA from total cellular RNA extracts of homogenized tissue specimens or in vitro grown cell populations. This technique is useful to assess the average expression of the 67 LR mRNA of a particular sample but does not provide information about expression in specific cell types nor about heterogeneity of expression from cell to cell. In this study, we analyzed the expression of 67 LR mRNA in four human cancer cell lines with varying degrees of expression of 67 LR protein (renal cancer A-704, breast carcinoma MCF-7/4 and MCF-7/7, and pancreatic cancer Panc-1) using in situ hybridization performed with 67 LR riboprobes. Total cellular RNA was simultaneously extracted from the cell lines and hybridized on Northern blots with a 67 LR cDNA probe to assess the validity of the mRNA detection by in situ hybridization. Sixty-seven LR mRNA expression was higher in Panc-1 and MCF-7/4 cells than in MCF-7/7 and renal carcinoma A-704. There was a direct correlation (R2 = 0.88) between the in situ hybridization analysis and the mRNA levels detected by Northern blot analysis. The in situ hybridization method showed a heterogeneous expression of the 67 LR mRNA in the four cell lines with different subpopulations of cells showing a range from negative to high levels of the message. Sixteen freshly frozen human colorectal tissues (seven adenocarcinomas, five matched normal mucosae, and four adenomas) were also analyzed by in situ hybridization. The 67 LR mRNA was localized in normal and neoplastic epithelial cells. Adenocarcinoma cells showed a 1.6- to 5-fold higher expression (P < 0.02 according to the Wilcoxon-Mann-Whitney test) than did epithelial colonic cells from normal mucosae or adenomas. The signal tended to be stronger in poorly differentiated carcinomas and carcinomas with metastases than in moderately differentiated and nonmetastatic tumors. We conclude that the high expression of 67 LR mRNA in colorectal tumors is due to an increased production by tumor cells. Furthermore, in situ hybridization is an effective method to detect the expression of LR mRNA in cultured cell lines as well as in frozen tissue sections. PMID- 1443046 TI - Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. AB - This study clarified whether and when the blood-brain barrier in experimental brain metastases is impaired by using hydrosoluble sodium fluorescein (MW 376) as a blood-brain barrier function indicator. Cells from eight human tumor lines (four melanomas, two breast carcinomas, one colon carcinoma, and one renal carcinoma) were inoculated into the internal carotid artery of nude mice. Brain metastases at different stages of development were sampled and the permeability of the blood-brain barrier around the metastases determined. Histologic examination showed two patterns of tumor growth. In the first, tumor cells formed isolated, well-defined nodules in the parenchyma of the brain. In lesions smaller than 0.2 mm2, the blood-brain barrier was intact. In the second, small diffuse nests of tumor cells were distributed throughout the brain parenchyma. The blood brain barrier was intact until the small tumor cell colonies coalesced to form large tumor masses. These results suggest that the permeability of the blood brain barrier varies among different experimental brain metastases and that its function is related to the growth pattern and size of the lesions. PMID- 1443047 TI - Expression of a chimeric helix-loop-helix gene, Id-SCL, in K562 human leukemic cells is associated with nuclear segmentation. AB - We have designed a chimeric gene, Id-SCL, in which the 3' helix-loop-helix encoding portion of the presumptive oncogene SCL/tal is joined to the 5' coding portion of Id, an inhibitory helix-loop-helix gene. The predicted protein product of this chimeric gene contains the helix-loop-helix dimerization domain of SCL/tal, but, lacking a basic DNA binding domain, is predicted to have the inhibitory function of the Id product. Expression of the Id-SCL fusion gene in stably transfected K562 cells reproducibly resulted in nuclear segmentation and depressed growth rates; both of these phenotypic effects demonstrated a dosage dependence on the levels of Id-SCL mRNA and protein expressed in the various clones. Electron microscopy of cells expressing high levels of Id-SCL mRNA showed a significant increase in cytoplasmic perinuclear thin filaments and diminution of marginal heterochromatin in the nuclei. No other changes in hematopoietic differentiation status were observed in association with Id-SCL expression. Expression of intact Id and SCL/tal genes, as well as deletion mutants of Id and SCL/tal, independently transfected into K562 cells, indicated that the nuclear segmentation effect is dependent on the presence of a protein possessing a helix loop-helix domain but lacking a basic domain. Our studies suggest that the balance of transcriptional inhibitory and stimulatory helix-loop-helix proteins in cells may be important determinants of proliferation and of structural organization within cells. PMID- 1443048 TI - Transplant arteriosclerosis in a rat aortic model. AB - Transplant arteriosclerosis (TA) has emerged as an obstacle to the long-term survival of transplanted organs, especially cardiac transplants. The animal models that have been used to study TA have not been fully characterized with regard to features such as the time course of cell proliferation and the sequence of cell types arriving in the developing intimal lesion. We present a model of TA based on a transplanted segment of abdominal aorta that helps address these questions. Two strains of rats (PVG x DA) underwent orthotopic aortic transplantation without immunosuppression and were killed at 14, 20, 40, and 60 days after transplantation. The within-strain control group displayed minimal evidence of cellular rejection with minimal to absent intimal lesions. In contrast, the allograft group showed a linearly increasing intimal lesion, up through 60 days after transplantation. The mechanism of intimal thickening was by an increase in cell number at the earlier time points with the later deposition of extracellular matrix. The early intimal lesion consisted mostly of mononuclear inflammatory cells (45%) with gradually increasing presence of smooth muscle cells (SMC) in the intima between 20 and 60 days. Conversely, the media showed gradual infiltration by macrophage-type cells with virtual loss of all SMC from the media by 40 days. The proliferative index showed a peak of 6% and 8% at 20 days in both the intima and media, respectively, and was preceded by the presence of macrophages. In fact, most of the proliferating cells at the earlier time points were either monocytes/macrophages, or were immediately adjacent to monocyte-/macrophage-rich regions. This straight artery segment model of transplant arteriosclerosis provides an easily quantifiable system in which the effects of different interventions (e.g., immunosuppressive regimens) can be tested. PMID- 1443049 TI - The genesis of the senile plaque. Further evidence in support of its neuronal origin. AB - Senile plaques are among the most conspicuous neuropathologic changes found in the brains of elderly individuals and patients with Alzheimer's disease (AD). The origin of the amyloid beta protein (A beta P) that accumulates in senile plaques continues to be highly controversial. Recently, using quantitative immunohistochemistry and computerized image analysis, we obtained evidence that at least a subset of early ("diffuse") senile plaques originate from neurons. In the current investigation, we employed monoclonal antibodies to A beta P and the same computerized methodology to examine in further detail the quantitative patterns of A beta P deposition in diffuse plaques in a population of intellectually intact elderly individuals. The presence of neurocentric concentration gradients of A beta P accumulation was confirmed in this study. Most significantly, this was the most predominant pattern of early amyloid deposition in the population studied. The highest concentration of A beta P was centered around neuronal cell bodies or their processes, and occasionally along neuronal plasma membranes. Computerized images showed patterns that can be interpreted as a pathogenetic sequence ranging from initial neurogenic concentration gradients centered around one single neuron to larger deposits (diffuse plaques) composed of several "anastomosing" gradients involving several adjacent neurons. It is proposed that the described very early deposits constitute the initial stage in the development of the senile plaque. Although this study does not fully prove that the accumulated A beta P is synthesized in the neuron or neuronal process it surrounds, the images herein presented suggest that neurons are the initial nidus of plaque formation. PMID- 1443051 TI - Cystitis induced by infection with the Lyme disease spirochete, Borrelia burgdorferi, in mice. AB - Previous studies have demonstrated that the urinary bladder is a consistent source for isolating the Lyme disease spirochete, Borrelia burgdorferi, from both experimentally infected and naturally exposed rodents. We examined histopathologic changes in the urinary bladder of different types of rodents experimentally infected with Lyme spirochetes, including BALB/c mice (Mus musculus), nude mice (M. musculus), white-footed mice (Peromyscus leucopus), and grasshopper mice (Onychomys leucogaster). Animals were inoculated intraperitoneally, subcutaneously, or intranasally with low-passaged spirochetes, high-passaged spirochetes, or phosphate-buffered saline. At various times after inoculation, animals were killed and approximately one-half of each urinary bladder and kidney were cultured separately in BSK-II medium while the other half of each organ was prepared for histologic examination. Spirochetes were cultured from the urinary bladder of all 35 mice inoculated with low-passaged spirochetes while we were unable to isolate spirochetes from any kidneys of the same mice. The pathologic changes observed most frequently in the urinary bladder of the infected mice were the presence of lymphoid aggregates, vascular changes, including an increase in the number of vessels and thickening of the vessel walls, and perivascular infiltrates. Our results demonstrate that nearly all individuals (93%) of the four types of mice examined had a cystitis associated with spirochetal infection. PMID- 1443050 TI - Integrin distributions in renal cell carcinomas of various grades of malignancy. AB - We studied 41 renal cell carcinomas, classified according to histologic grades G1 through G3, by indirect immunofluorescence microscopy using a panel of monoclonal antibodies (MAb) against various integrin subunits, and the basement membrane (BM) components laminin and collagen type IV. Selected cases also were immunostained using the avidin-biotin-complex method. The alpha 3 and beta 1 integrin subunits were detected in tumor cells of all the carcinomas. All G1 carcinomas, like normal tubular epithelial cells, expressed the alpha 6 subunit, whereas it was lacking in 20% and 40% of G2 and G3 carcinomas, respectively. Furthermore, when alpha 6 was expressed, a lack of basally polarized organization of the subunit, coupled with disorganization of the BM components, correlated with histologic grade. Another feature that appeared to characterize the more anaplastic tumors was their high level (80%) of the alpha v subunit expression as compared with its absence in the G1 carcinomas. Stromal myofibroblasts, identified by double-labeling with anti-myosin, were often characterized by the expression of the alpha 1, alpha 3, alpha 5 and beta 1 subunits. These results indicate that changes in integrin expression in renal cell carcinomas may be correlated with their degree of histologic malignancy. PMID- 1443052 TI - Anthracyclines selectively decrease alpha cardiac actin mRNA abundance in the rat heart. AB - Anthracyclines are widely used antineoplastic agents, but possess a major side effect of congestive cardiomyopathy. Previously we showed a selective effect of the most commonly used anthracycline, doxorubicin, on decreasing alpha-cardiac (alpha c) actin mRNA abundance in the rat heart. The current studies examined the effects of several anthracyclines (doxorubicin, daunorubicin, and epirubicin) to determine if doxorubicin's previously reported effect on alpha c actin mRNA abundance is: 1) a property shared by other cardiotoxic anthracyclines; 2) selective when compared with a wider spectrum of contractile protein and muscle specific mRNAs; and 3) related to the characteristic ultrastructural alterations, such as loss of myofilaments, seen in anthracycline-induced cardiomyopathy. Results showed a major selective effect of doxorubicin, daunorubicin, and epirubicin on decreasing alpha c actin mRNA abundance when compared with other contractile protein and muscle-specific mRNAs. In addition, ultrastructural examination of myocardium showed contractile alterations, including loss of myofilaments. These results suggest that decreased expression of selected cardiac genes may relate to the molecular mechanism of clinical anthracycline-induced cardiomyopathy. PMID- 1443053 TI - Efficacy of monoclonal antibody against human recombinant tumor necrosis factor in E. coli-challenged swine. AB - Monoclonal antibody against human tumor necrosis factor alpha (TNF MAb) prevents death induced by intravenous gram-negative bacteria or lipopolysaccharide (LPS) in primates. Although these studies have demonstrated that TNF plays a prominent role in the development of lethal septic shock, exploration of dose-response relationships and possible mechanisms of protection have been limited. We addressed these questions in a series of experiments conducted in E. coli challenged pigs. First, we determined that TNF MAb neutralized the cytotoxic activity found in septic pig plasma and in culture media from pig monocytes incubated with LPS. Second, we demonstrated that pretreatment with TNF MAb promotes survival, in a dose-dependent fashion, in an otherwise lethal E. coli bacteremic pig model. The results of the survival study highly correlate (r = 0.96, P < 0.01) the presence of TNF in the circulation with mortality. In an additional series of physiologic monitoring experiments designed to delineate possible mechanisms of protection, the authors demonstrate that TNF MAb pretreatment abrogates the prolonged leukopenia, thrombocytopenia, and microvascular leakiness resulting from intravenous bacterial challenge and maintains arterial blood pressure while diminishing pulmonary edema. These findings may provide a mechanism whereby neutralization of TNF systemically affords protection against the lethal sequelae of bacteremia. PMID- 1443054 TI - Different patterns of macrophage infiltration into allogeneic-murine and xenogeneic-human neoplasms growing in nude mice. AB - This study determined the distribution pattern of tumor-associated macrophages (TAM) in murine and human neoplasms growing subcutaneously in nude mice. Seven different human neoplasms (cancers of the breast, kidney, colon, prostate, lung, and skin, and a melanoma) and five different murine neoplasms (carcinomas of the lung, colon, and kidney, melanoma, and fibrosarcoma) were injected into nude mice. The murine tumors also were injected into syngeneic mice. Tumor-associated macrophages in small and large tumors were studied immunohistochemically by the use of several antibodies, including the macrophage-specific F4/80. The pattern of TAM distribution differed between mouse and human tumors. Regardless of histologic classification, TAM were uniformly distributed throughout all the murine neoplasms growing in syngeneic or nude mice. In the human neoplasms, TAM were found on the periphery of the lesions and in association with fibrous septae. The distribution of TAM in murine and human tumors was associated with a pattern of vascularization as determined by antibodies to basement membrane collagen type IV. Because the pattern of TAM distribution in neoplasms influences their antitumor activity, the data question the validity of the nude mouse model for the study of macrophage infiltration into human neoplasms. PMID- 1443056 TI - The proliferation of rhetoric and the poverty of ideas. PMID- 1443055 TI - A recessive defect in lymphocyte or granulocyte function caused by an integrated transgene. AB - A line of transgenic mice has been identified with a recessive defect in lymphocyte or granulocyte function, presumably as a result of insertional mutagenesis by the integrated transgene. Transgenic mice homozygous for the transgene integrant showed nearly complete absence of lymphocytes in peripheral lymph nodes and Peyer's patches, a severely diminished thymus medulla, and a greatly enlarged spleen. These animals also developed a syndrome characterized by granulocyte and mononuclear infiltrates in numerous tissues, including skin, liver, and lung, and immunoglobulin deposits in kidney glomeruli. Lung infiltrates were specifically localized around large blood vessels and bronchi, accompanied in some cases by destruction of arterial walls. The light scatter profile of spleen lymphocytes suggested an extremely high percentage of blast cells. Because tissue development and morphology appears to be normal in all other tissues observed, the genetic lesion appears to specifically affect the regulation of lymphocyte or granulocyte activation. PMID- 1443057 TI - Bereavement support groups for school-age children: theory, intervention, and case example. AB - Children's bereavement support groups can provide useful surrogate support for families when a parent dies, and may contribute new social meaning for this traumatic event. Theories and techniques for intervention in such groups are presented and their application illustrated via a clinical case history. Results indicate that categorization of children's bereavement should be abandoned in favor of conceptualization in terms of prior adaptation processes. PMID- 1443058 TI - Detachment revisited: the child's reconstruction of a dead parent. AB - During the year following a parent's death, children in a community-based sample were found to have developed an inner construction of the dead parent. This continued, though altered, relationship appeared to facilitate their coping with the loss and with accompanying changes in their lives. Implications for understanding the bereavement process and for interventions focusing on detachment are discussed. PMID- 1443059 TI - Childhood parental death and depression in adulthood: roles of surviving parent and family environment. AB - Among adults who experienced a childhood parental death, measures of depression were influenced by interactions with the surviving parent and by the nature of the family environment after the death. Individuals describing their surviving parent as empathic and warm, and as promoting autonomy, were less likely to report depressive experiences than were others. Less opportunity for participating in the mourning process was also associated with greater risk for depression. PMID- 1443060 TI - Parental death in childhood: perceived vulnerability, and adult depression and anxiety. AB - College students who had experienced the death of a parent during their childhoods perceived themselves as more vulnerable to future losses than did a nonbereaved control group. Perceived vulnerability to loss was identified as a better predictor of adult anxiety and depression than was the early loss itself. Perceived vulnerability to loss is thus implicated in the development of adult psychopathology associated with early loss. PMID- 1443061 TI - Victimization and traumatic injuries among the homeless: associations with alcohol, drug, and mental problems. AB - Data from a 1987 survey of 1,260 homeless adults in New York City show that mental problems and substance dependence were significantly linked to beating and sexual assault among women and to several types of injury and victimization among men. The extremely high rates of victimization and injury underscore a need for greater attention to the safety and welfare of homeless people. PMID- 1443062 TI - Early life experiences and residential stability: a ten-year perspective on sheltered care. AB - The effects of early family losses and disruptions on the ability of seriously mentally disabled individuals to achieve stable living arrangements were investigated. Factors found to predict instability were early losses, early disruptions, psychological symptoms, and youth. Among factors found to predict stability were increased age and a diagnosis of schizophrenia. PMID- 1443063 TI - Recent trauma in psychiatric outpatients. AB - Psychiatric clinic outpatients were screened for recent traumatic events, and post-traumatic symptomatology was evaluated in those reporting occurrence of one or more events within the two years prior to screening. Clear symptoms of post traumatic stress disorder were revealed in 18% of the reporting patients, and the distribution of diagnoses was found to be different in the trauma-reporting group than it was in a comparison diagnostic group. PMID- 1443064 TI - Marital satisfaction among parents of the severely mentally ill living in the community. AB - Factors influencing marital satisfaction among 131 parents of adult offspring with severe mental illness were explored. Those found to be most predictive of marital satisfaction were parents' ability to comfort one another, parents' gender, number of offspring, family income, and interpersonal sensitivity. Implications of these findings for practical and policy approaches to preventive intervention are discussed. PMID- 1443065 TI - Temperament and adjustment in young adulthood: a 15-year longitudinal analysis. AB - The relationship between easy/difficult temperament and adjustment from middle adolescence to young adulthood was examined. Cluster analysis revealed four groups of individuals via composite temperament scores over three points of measurement. Multivariate analyses indicated that extremely difficult temperament was associated with poorer psychosocial functioning in childhood and young adulthood. PMID- 1443066 TI - Long-term effectiveness of a group program for caregivers of frail elderly veterans. AB - Long-term results of an evaluation of a multicomponent support-group program for spouses caring for frail elderly veterans indicated that participants experienced significant reductions in subjective burden. As compared to those of the control group, caregivers' perceptions of their husbands' health improved significantly from pretest to one year, while perceptions of their husbands' functioning on measures of instrumental daily activities showed significantly less deterioration in the period from pretest to posttest. PMID- 1443067 TI - Locus of control as a mediator of negative divorce-related events and adjustment problems in children. AB - Beliefs about whether locus of control mediates the relationship between negative divorce-related events and children's adjustment were explored in a group of 78 children and their primary residential parents. In the children's self-reports of adjustment, locus of control was found to be a partial mediator in the relationship. Analyses of the parents' reports of the children's adjustment did not support a mediational model. PMID- 1443068 TI - Impact on children of abduction by a parent: a review of the literature. AB - It is estimated that 350,000 children are abducted by members of their families annually. A review of the published research reveals that little is known about the impact of this traumatic event on the children. Factors reported to affect their functioning after recovery by the searching parent are identified, and implications for further research are suggested. PMID- 1443069 TI - Functional somatic symptoms: a cross-ethnic comparison. AB - Type, distribution, and comorbidity of functional somatic symptoms were examined in four community samples, three Hispanic and one non-Hispanic white. Important intergroup and intragroup differences between Hispanic and non-Hispanic white groups were identified. Of the four groups, Puerto Rican respondents reported the highest level of somatic symptoms; this finding was apparently independent of sociodemographic factors. PMID- 1443070 TI - Family functions and children's postdivorce adjustment. AB - Data on school-age children of divorced parents were examined to determine which dimensions of family dynamics were most associated with the children's socioemotional adjustment. Those factors found to be most significant were family roles, behavior control, and affective involvement, as well as children's reaction to and insight into the divorce, and conflict in the home after the divorce. Implications for parent education and early intervention are discussed. PMID- 1443072 TI - Creativity: the key to progress. PMID- 1443071 TI - Self-structure in borderline personality disorder. AB - Self-structural theory is applied to the interpersonal aspects of borderline personality disorder. The notion of interpersonal contrasting, a cognitive maneuver, is introduced to account for the sharp changes between divergent self states characteristic of the disorder. The theory and three prototypical self states are illustrated with data from a borderline patient by means of a procedure derived from the theory. PMID- 1443073 TI - Hearing results from endolymphatic sac surgery. AB - This report examines the effect of the endolymphatic shunt on hearing. The study group was drawn from 101 shunt operations for intractable vertigo between 1983 and 1987. Thirty ears met criteria for diagnosis, level of preoperative hearing impairment, and length of follow-up. The control group consisted of 30 ears with symptoms severe enough to prompt recommendations for shunt surgery, but the patients either opted against surgery or improved. The results were analyzed using the 1985 AAO-HNS reporting criteria. When looking at worst postoperative (or worst scores after 2 years of follow-up in controls) compared to worst preoperative (or worst scores in the first 6 months of presentation in controls), we found no significant difference between the study group (average loss of 9 dB pure-tone average [PTA] and 16% speech discrimination [SD]) as compared to the control group (average loss of 3 dB PTA and 10% SD). However, when using the first and last audiograms for the control group, there was a statistically significant difference as compared to the worst preoperative and postoperative scores in the shunt group. Using the first and last scores, the control group had a better outcome (PTA improved 2 dB, SD score dropped 5%). There was no significant difference between groups for percentage of patients whose hearing improved, remained the same, or worsened. In conclusion, the endolymphatic shunt operation did not significantly effect the long-term hearing results. PMID- 1443074 TI - Aberration of the tissue collagenase system in association with otosclerosis. AB - Studies of aural and other body tissues suggest that otosclerosis represents the local manifestation of a general disorder of connective tissue. In particular, collagen abnormalities have been described. We have undertaken a pilot study of the in vivo messenger RNA (mRNA) transcription for procollagenase (precursor of collagenase), as well as for stromelysin and tissue inhibitor of metalloprotease (TIMP), an activator and a specific inhibitor of tissue collagenase activity, respectively. Human skin from individuals with surgically confirmed otosclerosis was compared to skin from their family members (clinically positive and clinically negative) and from unrelated normal controls. Preliminary data indicate that on average there are significantly lower levels of mRNA production for stromelysin among individuals with otosclerosis as compared to all others tested. Similar trends were demonstrated for TIMP and procollagenase, although these did not achieve statistical significance. In addition to suggesting a pathogenetic mechanism for the development of the disease, these data could serve as the basis of possible confirmatory tests for early diagnosis of otosclerosis and as a method for evaluating the genotype of offspring of affected individuals prior to their age of clinical manifestation. This could translate into the application of prophylactic treatment regimens in the future. The proposed abnormalities also suggest candidate genes for otosclerosis. PMID- 1443075 TI - Transcochlear transtentorial approach for removal of large cerebellopontine angle meningiomas. AB - Meningiomas of the cerebellopontine angle (CPA) most often arise from the posterior surface of the petrous pyramid and may extend along the dura to involve the tentorium. Petroclival meningiomas often involve Meckel's cavity and the tentorium. It is impossible to completely remove these large lesions with extension to the supratentorial region by conventional surgical approaches to the CPA such as the suboccipital, middle fossa, or translabyrinthine routes. If total tumor resection is not accomplished, recurrence inevitably follows. A transcochlear approach and actual excision of a large portion of the tentorium allows wide exposure to these large CPA and petroclival meningiomas with supratentorial extension. Thirty-three CPA meningiomas were reviewed from 1976 to 1991. Fourteen patients had tumor extension not only into Meckel's cavity but to the supratentorial region. Ten patients had complete tumor removal, whereas subtotal removal was associated with cavernous sinus invasion. The surgical technique is described in detail with accompanying illustrations. Preoperative symptoms, medical imaging scans, results, and complications are discussed. PMID- 1443076 TI - Labyrinthotomy with streptomycin infusion: early results of a multicenter study. The LSI Multicenter Study Group. AB - Early results for hearing and vertigo are reported for 47 labyrinthotomies with streptomycin infusion (LSI) by 13 coinvestigator-surgeons. Sixty-eight percent of patients had worse hearing after surgery (10 dB or 15% word recognition). Patients with a preoperative pure-tone average better than or equal to 40 dB appeared to suffer less postoperative hearing loss than those with a greater preoperative deficit. Severe to profound postoperative hearing loss was experienced by 27 patients (57%), all of whom had preoperative pure-tone averages worse than 40 dB. Opening the endolymphatic space was associated with a deleterious effect on hearing. Because of persistent vertigo, 17 percent of patients required a secondary procedure during the period of observation. These early results indicate that LSI is associated with a significant risk of postoperative hearing loss. Of the 13 coinvestigator-surgeons, four have stopped using LSI, while one considers his results satisfactory. The remaining surgeons have taken an intermediate position and feel it is useful in selected cases. Longer follow-up is required to judge the efficacy of LSI for controlling vertigo. We are currently studying these long-term results. PMID- 1443077 TI - Retrolabyrinthine transtentorial approach to lesions of the anterior cerebellopontine angle. AB - Various surgical approaches to the cerebellopontine angle have been used for removal of acoustic neuromas. A retrolabyrinthine transtentorial approach has been developed that allows (1) access to the anterior cerebellopontine angle and all portions of the basilar artery, (2) extra dural retraction of the lateral sinus and cerebellum while avoiding the vein of Labbe, and (3) preservation of hearing. This approach allows good exposure of tumor and accurate visualization of cranial nerves. To avoid complications, control of spinal fluid is mandatory and great care must be taken to avoid injury of the cranial nerves. The retrolabyrinthine or translabyrinthine transtentorial approach enables skilled neurosurgeons and neurotologists to gain access to lesions that are located in areas difficult to approach. PMID- 1443078 TI - Differential diagnosis of virus-like particles in the human inner ear. AB - The entire endolymphatic duct and sac as well as the vestibular epithelia were obtained from four patients with Meniere's disease during translabyrinthine (TL) eighth nerve section and from 12 patients undergoing TL resection of acoustic schwannomas. After these specimens were processed for routine transmission electron microscopy (TEM), they were studied for morphologic evidence of viral infection. Although no virus particles were identified, numerous regularly occurring cell components and artifacts were found to morphologically mimic viruses. An atlas of these structures is presented. PMID- 1443079 TI - Aspartame and dizziness: preliminary results of a prospective, nonblinded, prevalence and attempted cross-over study. AB - Aspartame is a low-calorie food sweetener recently approved by the FDA for general human consumption. One of us (AJG) treated a patient whose symptoms of episodic vertigo and continuous unsteadiness resolved upon ceasing aspartame intake. A literature review revealed that although dizziness has been associated with aspartame intake, no systematic study of the problem exists. As an initial attempt to ascertain the prevalence of aspartame-related dizziness in an otolaryngologic clinic, we elected to study prospectively all patients entering with the complaint of vertigo by means of a standardized questionnaire. Those patients determined to consume aspartame were further studied in a nonblinded manner to see if aspartame intake could be correlated to symptomatology. A cross over limb was also attempted, but no patient would participate. This presentation details the case history of the propositus patient and the preliminary results of the currently ongoing prospective study. PMID- 1443080 TI - System identification of perilymphatic fistula in an animal model. AB - An acute animal model has been developed in the chinchilla for the study of perilymphatic fistulas. Micropunctures were made in three sites to simulate bony, round window, and oval window fistulas. The eye movements in response to pressure applied to the external auditory canal were recorded after micropuncture induction and in preoperative controls. The main pressure stimulus was a pseudorandom binary sequence (PRBS) that rapidly changed between plus and minus 200 mm of water. The PRBS stimulus, with its wide frequency bandwidth, produced responses clearly above the preoperative baseline in 78 percent of the runs. The response was better between 0.5 and 3.3 Hz than it was below 0.5 Hz. The direction of horizontal eye movement was toward the side of the fistula with positive pressure applied in 92 percent of the runs. Vertical eye movements were also observed. The ratio of vertical eye displacement to horizontal eye displacement depended upon the site of the micropuncture induction. Thus, such a ratio measurement may be clinically useful in the noninvasive localization of perilymphatic fistulas in humans. PMID- 1443081 TI - Evaluations of 3M/House single-channel and nucleus multichannel cochlear implants. AB - 3M/House single-channel (n = 158) and Nucleus multichannel (n = 71) adult cochlear implant users were surveyed about their devices. In comparison to the 3M/House users, the Nucleus users reported better speech and environmental sounds perception and more hours of daily use. However, Nucleus users also were more likely to report that the expense of upkeep and frequent movement of external parts of their implants were problems. On average, users in both groups were satisfied and felt that their implants had positively affected their lifestyle, enjoyment of social events, and employability. Differences between groups regarding these variables were not found. Multiple regression indicated that the users' ratings of the effects of their implants on speech perception, environmental sounds perception, enjoyment of social events, and lifestyle were all statistically significant predictors of satisfaction. It was concluded that the majority of the users in either group thought their devices provided real world benefits. PMID- 1443082 TI - Reconstruction of the radical mastoid. AB - Open cavity techniques (radical mastoidectomy, canal wall down tympanomastoidectomy, modified radical mastoidectomy) are well established surgical procedures for the treatment of chronic otitis media. Despite their effectiveness in exteriorizing cholesteatoma, they are associated with a 20 to 60 percent incidence of persistent intermittent drainage. In an effort to eliminate this problem, we have employed a Palva flap and medial graft technique to reconstruct the mastoid cavity and middle ear space in those patients with chronically draining ears. Between 1987 and 1990, 28 patients underwent this procedure. Twenty-six of these (93%) had complete obliteration of the mastoid cavity and successful tympanic membrane reconstruction. Two of 28 (7%) had a persistent tympanic membrane perforation and intermittent drainage following their surgery. Based on these results, this procedure is effective in eliminating intermittent drainage associated with the open cavity techniques. The indications for this procedure, the specifics of the surgical technique, and the postoperative results are discussed. PMID- 1443083 TI - Geniculate ganglion: anatomic study with surgical implications. AB - The geniculate ganglion and adjacent segments of the facial nerve were dissected in 11 human temporal bones to study the extent and distribution of ganglion cells. A histologic basis for the use of geniculate ganglionectomy as the treatment for geniculate neuralgia was sought. In 9 of 11 specimens (81.8%), the ganglion cell bodies appeared to be aggregated at the apex of the genu close to the origin of the greater superficial petrosal nerve. The mean ratio of the width of the ganglion cell cluster to the width of the facial nerve trunk at the level of the genu was 0.4. In two specimens, significant anatomic variation was present. One specimen showed extension of cell bodies into the labyrinthine segment of the facial nerve; another specimen showed a single ganglion cell in the region of the genu. These findings lead us to postulate that geniculate ganglionectomy may be ineffective as the sole treatment for certain cases of geniculate neuralgia, and that nervus intermedius section may also be required to achieve a more complete deafferentation. PMID- 1443084 TI - Rhinorrhea after neurotologic surgery. AB - Rhinorrhea after neurotologic surgery may be indicative of a cerebrospinal fluid (CSF) leak or may be secondary to autonomic dysfunction as a result of injury to preganglionic parasympathetic fibers. Differentiation between these two conditions is essential because undetected CSF rhinorrhea may lead to meningitis and death. PMID- 1443085 TI - Meniere's disease in congenital nephrogenic diabetes insipidus: report of two twins. AB - Two cases, twins, affected by congenital nephrogenic diabetes insipidus (CNDI) with a high daily volume of dilute urine excretion and periods of compensatory high levels of antidiuretic hormone (ADH) simultaneously developed a fluctuating Meniere-type hearing loss. It is well known that the kidney and the cochlea are linked by structural and anatomic characteristics, as well as by the physiologic mechanism of electrolytes and fluid regulation. The patients herein described seem to be paradoxical, because they suffered from hydropic hearing loss despite the pathophysiologic mechanism of CNDI and the possible role played by ADH in water regulation in the inner ear. The consequences on Meniere's disease of the different therapeutic regimens followed by the two CNDI patients are discussed. To our knowledge these are the first cases of CNDI with Meniere's disease described in the literature. PMID- 1443086 TI - Very far-advanced otosclerosis. AB - The term very far-advanced otosclerosis is proposed to indicate otosclerotic patients with both bone and air conduction thresholds nonmeasurable on a standard clinical audiometer (blank audiogram). Three of these patients have undergone stapedotomy with satisfactory results. This confirms that cochlear implantation is not the best treatment for all profoundly deaf patients at least with implants available today. Some of the patients with a blank audiogram are better off with exploratory tympanotomy and stapedotomy. PMID- 1443087 TI - Case 1: Bell's palsy and persistent loss of taste. Case 2: Bell's palsy, dramatic recovery with high dose steroid therapy. PMID- 1443088 TI - Management of slowly progressive facial paralysis attributable to a tumor in the temporal bone. PMID- 1443089 TI - Stapedectomy modified by the application of fibrin tissue adhesive. PMID- 1443090 TI - Computed tomography and enamel thickness of maxillary molars of Plio-Pleistocene hominids from Sterkfontein, Swartkrans, and Kromdraai (South Africa): An exploratory study. AB - This paper is one in a series which explores the possibility of using the non destructive CT technique to identify patterns in tooth enamel distribution and structure of hominid molars from Plio-Pleistocene sites in South Africa, notably Swartkrans, Sterkfontein, and Kromdraai. Whereas previous investigators have emphasised gross differences in absolute and relative or average enamel thickness between hominid taxa, the present study highlights differences in enamel thickness over functionally significant regions of the crown. Differences in the distribution of enamel in A. robustus, A. africanus, and Homo sp. are identified through the use of bivariate and multivariate analyses, and are interpreted in terms of dietary regimes. PMID- 1443091 TI - Congenital syphilis in the past: slaves at Newton Plantation, Barbados, West Indies. AB - Hutchinson's incisors and Moon's molars are specific lesions of congenital syphilis. The extensive but fragmentary clinical literature on these conditions describes reduced dimensions and thin enamel in the permanent incisors and first molars, crowding and infolding of the first molar cusps, notching of the upper incisors, and apical hypoplasias of the permanent canines. A Barbados slave cemetery (ca. 1660-1820 AD) includes three individuals with these features, suggesting a frequency at birth of congenital syphilis in the population approaching 10%. These three cases show triple the frequency of all hypoplasias and more than seven times the frequency of pitting hypoplasia present in the remainder of the series. The recognizable congenital syphilis cases account for much of the remarkably high frequency of hypoplasias in the series as a whole. We infer that syphilis contributed substantially to morbidity, infant mortality, and infertility in this population. Presence or absence of congenital syphilis may account for much of the variability in health and mortality seen among nineteenth century African-American populations. PMID- 1443092 TI - Demography of the Hadza, an increasing and high density population of Savanna foragers. AB - This is a report on the demography of the Hadza, a population of East African hunter-gatherers. In it, we describe the results of a census, and our estimation of age structure, survivorship, mean age of women at childbearing, number of live children, total population size and density, and rate of change since 1967. We show that relevant measures fit closely the stable population model North 6 chosen by Dyson to represent Hadza demography in the 1960s. We compare aspects of Hadza demography with surrounding non-Hadza and with the !Kung. Among other things, we find that the Hadza have a higher population density, higher fertility, and a faster population growth rate than do the !Kung. These demographic differences are consistent with our expectations, which were based on differences in the costs and benefits of foraging in the two regions. We also show that Hadza demographic parameters display remarkable consistency over the past 20 years. Since neighboring populations have been encroaching on the area used by the Hadza, and Hadza foragers have been subject to interludes of externally imposed settlement, this consistency is surprising. We discuss some of the implications. PMID- 1443093 TI - Evaluation of lead concentrations in 18th-century Omaha Indian skeletons using ICP-MS. AB - The analysis of skeletal remains of Omaha Indians buried between AD 1780 and 1820 indicated that lead was incorporated in cortical bone. The diagenetic or biogenetic origin of the lead was evaluated by examination of lead isotope ratios of the bones and artifacts, and comparison of lead concentrations in burial soils with those of the bones. The isotopic values of the lead artifacts demonstrate that the lead was mined in the Missouri region. Although the isotope ratios in the bones are not identical with that from the lead artifacts, there is a strong relationship between them. This finding indicates that the lead in the bone was at least partly derived from the artifacts. Because lead artifacts rarely accompanied the burials but lead was ubiquitous in the bones, we suggest a biogenetic origin for the lead. There is also the possibility that some of the lead may have been derived from pigments applied to the corpse during mortuary ritual. PMID- 1443094 TI - Carbon and nitrogen stable isotopic signatures of human dietary change in the Georgia Bight. AB - Measurement of carbon and nitrogen stable isotope ratios (delta 13C and delta 15N) in samples of human bone collagen (n = 93) from a temporal series of four prehistoric (early preagricultural, late preagricultural, early agricultural, late agricultural) and two historic (early contact, late contact) periods from the Georgia Bight, a continental embayment on the southeastern U.S. Atlantic coast, reveals a general temporal trend for less negative delta 13C values and less positive delta 15N values. This trend reflects a concomitant decrease in emphasis on marine resources and increased reliance on C4-based resources, especially maize. This dietary reorientation is most apparent for the early agricultural sample (AD 1150-1300), coinciding with the Mississippian fluorescence in the eastern United States. There is, however, a shift toward the use of C3 (non-maize) foods during the last prehistoric period (AD 1300-1450), which is likely related to environmental stress and social disruption. A heavier use of maize and terrestrial resources in general after the establishment of mission centers on barrier islands is indicated. A reduced dietary breadth during the mission period may have contributed to the extinction of these populations in the eighteenth century. PMID- 1443095 TI - New species of bushbaby from the middle Miocene of Maboko Island, Kenya. AB - A mandible recovered from ca. 15 million year old deposits of Maboko Island, Kenya, represents the first bushbaby known from the middle Miocene. The specimen is from a new species of Komba, a genus previously known from early Miocene occurrences in western Kenya and northeastern Uganda. Komba is revised, with emended diagnoses proposed for the genus, type-species, and referred species. Komba sp. nov. is distinguished by its larger size and differences of molar cusp acuity, buccal cingulum expression, and mental foramen configuration. Contrary to previous opinion, species of Komba probably diverged prior to the last common ancestor of extant Galaginae, and it is unlikely that they represent early stages of living bushbaby species lineages. Although contemporary Progalago is widely regarded as a galagine, aspects of upper molar, lower premolar, and mandibular corpus morphology indicate that it is more closely related to lorisines. Unlike the greater success currently enjoyed by bushbabies, lorisines were more diverse and almost as abundant as galagines in the early Miocene of eastern Africa. PMID- 1443096 TI - Estimation of age structure in anthropological demography. AB - The past decade has produced considerable debate over the feasibility of paleodemographic research, with much attention focusing on the question of reliability of age estimates. We show here that in cases where age is estimated rather than known, the traditional method of assigning individuals to age classes will produce biased estimates of age structure. We demonstrate the effect of this bias both mathematically and by computer simulation, and show how a more appropriate method from the fisheries literature (the "iterated age length key") can be used to estimate age structure. Because it is often the case that ages are also estimated for extant groups, we suggest that our results are relevant to the general field of anthropological demography, and that it is time for us to improve the statistical basis for age structure estimation. We further suggest that the oft noted paucity of older individuals in skeletal collections is a simple result of the use of inappropriate methods of age estimation, and that this problem can be rectified in the future by using maximum likelihood estimates of life table or hazard functions incorporating the uncertainty of age estimates. PMID- 1443097 TI - Association of phospholipase C-delta with a highly enriched preparation of canine sarcolemma. AB - Myocardial synthesis of phosphatidylinositol 4,5-bisphosphate (PIP2) is highly compartmentalized in the sarcolemmal membrane. Sarcolemmal vesicles contain endogenous phospholipase C (PLC), but the identity of sarcolemmal PLC and its relationship to soluble PLC have not been determined previously. Sarcolemmal and cytosolic PLC were prepared from canine myocardium and characterized by DEAE cellulose chromatography and by immunoblotting with monoclonal and polyclonal antibodies to isoenzymes of PLC (PLC beta, PLC gamma, and PLC delta). DEAE cellulose chromatography resolved two forms of cytosolic PLC that were identified as an 85-kDa form of PLC delta and a 145-kDa form of PLC gamma. In contrast, DEAE cellulose chromatography resolved a single form of sarcolemmal PLC that was identified as an 85-kDa form of PLC delta. These data demonstrate that PLC gamma and PLC delta are expressed in canine myocardium and that an 85-kDa form of PLC delta is selectively associated with sites of PIP2 synthesis in a highly enriched preparation of sarcolemma. These data do not exclude the existence of additional isoenzymes of sarcolemmal PLC that may have been removed during isolation of sarcolemmal membranes. PMID- 1443098 TI - Oxygenation-activated K fluxes in trout red blood cells. AB - The effect of oxygenation on the dissipative fluxes of K in trout red blood cells has been determined. Unidirectional influx under low oxygen tension (PO2 = 1 kPa) was 0.56 +/- 0.07 mmol.l-1 packed cells.h-1. Within a few minutes of equilibration with high oxygen tension (PO2 = 120 kPa), influx was increased 14 fold, and this was associated with a progressive loss of KCl and a cell shrinkage. K influx progressively declined over the following 3 h to levels close to those characteristic of cells at low oxygen tension. Replacement of medium Cl by NO3- or methane sulfonate inhibited the stimulation due to high oxygen as did furosemide and low extracellular pH. The oxygenation-stimulated influx was highly volume sensitive, being increased by up to 100% by osmotic swelling and decreased by osmotic shrinkage. By contrast, the small influx under low oxygen tension was unaffected by either Cl replacement or by shrinkage and increased only with extreme swelling. Thus high oxygen tension activated a Cl-dependent and furosemide-sensitive K flux. Once activated, the mechanism was rapidly deactivated on transfer back to low oxygen tension but slowly deactivated when maintained at high PO2. The oxygenation-stimulated flux mechanism promotes a rapid and more complete volume regulatory decrease than in cells at low oxygen tension. PMID- 1443099 TI - Effect of fatigue on rate of isometric force development in mouse fast- and slow twitch muscles. AB - Changes in the rate of isometric force development with fatigue were measured in vitro (25 degrees C) using mouse soleus and extensor digitorum longus (EDL) muscles. Muscles were fatigued using 30 tetanic contractions. Rate of force development was determined from the rate constant of an exponential curve fitted to the rising force phase of a tetanus. For both muscles, when the intertetanus interval was 3 s, maximum isometric force and relaxation rate were significantly reduced in the final tetanus relative to the values in the first tetanus. Rate of force development in soleus muscles transiently increased and then decreased a small amount. The final rate was 92.7 +/- 3.3% (n = 4) of the initial rate. In contrast, the rate of force development in EDL muscles increased to 133.7 +/- 3.3% (n = 4) of the initial rate. This increased rate was evident from the second tetanus of the series, was fully established after 5 tetani, and the magnitude of the increase in rate was inversely proportional to intertetanus interval and was independent of presumed energy expenditure. The enhanced rate decayed with a time constant of 14.3 +/- 2.0 s and was independent of presumed energy expenditure. Most of these observations can be explained by the effects of P(i) on cross bridge kinetics. Other possible mechanisms, involving more rapid activation, are also suggested. PMID- 1443100 TI - Effects of intracellular ions on interleukin-1 beta production by lipopolysaccharide-activated human monocytes. AB - Following the observation that interleukin 1 beta (IL-1 beta) production in lipopolysaccharide (LPS)activated monocytes increases in concert with a rise in intracellular pH (pHi), the role of ion transport in IL-1 beta production was investigated. The amiloride analogue 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na(+)-H+ antiporter, inhibited extracellular IL-1 beta. The replacement of Na+ in the culture medium with sucrose or choline chloride also prevented monocyte activation. The sodium ionophore monensin, in doses from 100 pM to 1 microM, potentiated LPS-stimulated extracellular IL-1 beta when compared with LPS alone. In the absence of LPS activation, monensin by itself at 10 nM stimulated IL-1 beta production to 63%. EIPA at 10 microM inhibited the Na+ influx, the rise in pHi, and intra- and extracellular IL-1 beta production in activated monocytes; this inhibition was reversed by 10 nM monensin. In the absence of bicarbonate, or in the presence of 10 microM 4,4' diisothiocyanostilbene-2,2'-disulfonic acid, the pHi of activated monocytes and the total protein synthesis did not change, but the production of IL-1 beta was inhibited. The data suggest that the stimulated influx of Na+ via the Na(+)-H+ antiporter regulates both pHi and IL-1 beta production in LPS-activated monocytes. The requirement for bicarbonate indicates an additional mechanism(s), separate from the modulation of pHi and intracellular Na+. PMID- 1443101 TI - Chemical modification of Ca(2+)-activated potassium channels of GH3 anterior pituitary cells. AB - The effects of amino group specific reagents were examined on single, large conductance, Ca(2+)-activated, K+ channels in excised membrane patches from GH3 cells. The reagents used include trinitrobenzene sulfonic acid, 4,4' diisothiocyanostilbene-2,2'-disulfonic acid and its 4-acetamido derivative, and sulfophenyl-isothiocyanate. These reagents react covalently with peptide terminal amino groups and the epsilon amino groups of lysine residues, thereby removing positive charge. Internal application of 0.1-1.0 mM reagent to inside-out patches irreversibly increases channel open probability. Single-channel conductance and voltage sensitivity are not affected by modification. Analysis of channel openings and closures shows that the increase in open probability is predominantly due to the loss of long-duration closures of the channel; however, the lengths of long-duration openings are increased. After the modification in the presence of Ca2+ was performed, the channel open probability remains large, regardless of the internal Ca2+ concentration. Transitions among several open and closed states of the modified channel are present in the absence of Ca2+, suggesting that many state transitions are not directly dependent on Ca2+ binding or dissociation. PMID- 1443102 TI - Delayed shortening and shrinkage of cochlear outer hair cells. AB - Slow shortening of cochlear outer hair cells has been speculated to modify cochlear sensitivity. Tetanic electrical field stimulation of isolated outer hair cells from guinea pigs shortened the cells for 2-3 min. Electrical stimulation reduced cell length and volume (-13.5 +/- 1.5 and -37.3 +/- 3.0% of initial values, respectively, n = 16) and decreased the intracellular Cl- concentration. Cytochalasin B (100 microM) inhibited electrical stimulation-induced shortening but not volume reduction. The following chemicals or manipulations inhibited the responses: 10 microM furosemide, 0.1 mM 4,4'-diisothiocyanostilbene-2,2' disulfonic acid (DIDS), 1 mM anthracene-9-carboxylic acid (AC9), 25 mM tetraethylammonium, 2.3 microM charybdotoxin (ChTX), 250 nM omega-conotoxin, and Ca(2+)-free medium. These findings suggest that both electrical stimulation induced shortening and shrinkage of outer hair cells result not only from an actin-mediated contractile force, but also from Cl- efflux through furosemide-, DIDS-, and AC9-sensitive Cl- channels, and K+ efflux through ChTX-sensitive K+ channels. PMID- 1443103 TI - Interaction of TPA and ultraviolet B radiation in regulation of ODC gene expression in rat keratinocytes. AB - Ultraviolet B radiation (UVB) and phorbol esters are known to promote tumor formation in skin; however, the interaction between UVB and phorbol esters in the regulation of gene expression remains incompletely understood. To define the interaction of UVB and phorbol esters in the control of keratinocyte gene expression, we have studied the effects of the phorbol ester 12-O tetradecanoylphorbol-13-acetate (TPA) and UVB on the regulation of ornithine decarboxylase (ODC) gene expression in a rat keratinocyte cell line. Both UVB and TPA alone increased ODC activity and induced the expression of the ODC gene. The combination of UVB and TPA produced a further increment in ODC gene expression at 12 h, but UVB markedly attenuated the TPA induction of ODC mRNA transcripts at 3 h. Protein synthesis inhibition with cycloheximide also induced ODC mRNA transcripts, but did not eliminate the further induction of ODC gene expression by UVB or TPA. No changes in actin gene expression following exposure to TPA/UVB were detected in the same experiments. UVB and TPA alone or in combination had no effect on the transcriptional activity of an ODC-chloramphenicol acetyltransferase fusion gene in transfected rat keratinocytes. The results of these studies suggest a complex posttranscriptional interaction of phorbol esters and UVB in the control of keratinocyte gene expression. PMID- 1443104 TI - Erythrocyte K-Cl cotransport: properties and regulation. AB - Erythrocytes possess a Cl-dependent, Na-independent K transport system cotransporting K and Cl in a 1:1 stoichiometry that is membrane potential independent. This K-Cl cotransporter is stimulated by cell swelling, acidification, Mg depletion, and thiol modification. Cell shrinkage, elevation of cellular divalent ions, thiol alkylation, phosphatase inhibitors, and derivatives of certain loop diuretics and stilbenes are inhibitory. Thus regulation of K-Cl cotransport at the membrane and cytoplasmic levels is highly complex. Basal K-Cl cotransport decreases with cellular maturation, whereas its modes of stimulation and inhibition are variable between species. The physiological inactivation appears to be prevented in low-K animal erythrocytes. In certain human hemoglobinopathies, K-Cl cotransport may be the cause of cellular dehydration and volume decrease. K-Cl cotransport occurs also in nonerythroid cells, such as in epithelial and liver cells of other species. At the threshold of molecular characterization, this comprehensive review places our present understanding of the mechanisms modulating K-Cl cotransport physiologically and pathophysiologically into kinetic and thermodynamic perspectives. PMID- 1443105 TI - Potentiation of twitch contraction in guinea pig ureter by sodium vanadate. AB - The effect of sodium vanadate on action potential and twitch contraction of guinea pig ureter was studied and compared with that of ouabain, elevated K+, low temperature, and a Ca agonist (BAY K 8644), which can be expected to exert certain comparative effects. Sodium vanadate markedly potentiated twitch contraction. Potentiation by vanadate was associated with marked prolongation of relaxation time. Sodium vanadate caused only slight depolarization of the membrane but marked changes in action potential. The duration of action potential was prolonged and the number of oscillatory spike potentials increased. These effects were different from those of other treatments. It is concluded that prolongation of action potential and the increase in the number of spikes are the main cause of potentiation of twitch contraction by sodium vanadate. In addition, inhibition of Ca pump activity of the smooth muscle membrane system by vanadate might also be involved in potentiation of twitch contraction. PMID- 1443106 TI - Kinetics of nucleocytoplasmic Ca2+ transients in DDT1 MF-2 smooth muscle cells. AB - The free calcium concentrations in the nucleus ([Ca2+]n) and in the cytoplasm ([Ca2+]c) of cultured DDT1 MF-2 smooth muscle cells were estimated using the fluorescent dye indo-1. With the use of confocal microscopy, line scans were made during the onset and the differential rise of the Ca2+ signal elicited by the agonists histamine and ATP. The results confirm our earlier findings that in these cells [Ca2+]n at rest was lower than [Ca2+]c. The present experiments show that this gradient over the nuclear envelope was also preserved in Ca(2+)-free solution containing 2 mM EGTA, underlining the selective barrier function of the nuclear envelope. During stimulation with histamine, an early Ca2+ rise in the vicinity of the nuclear envelope was found in contrast to the delayed Ca2+ rise 2 microns away on both sides of the envelope. This suggests the release of Ca2+ stored in the envelope and the perinuclear sarcoplasmic reticulum. The time course for reaching a uniform Ca2+ concentration ([Ca2+]u = [Ca2+]n = [Ca2+]c) in the nuclear and cytosolic compartment varied with the agonist used for stimulation and was dependent on the external Ca2+ concentration. The value of this uniform Ca2+ concentration itself was, however, independent of the type of stimulation. After reaching [Ca2+]u, a further rise occurred with [Ca2+]n becoming larger than [Ca2+]c. It is postulated that a critical Ca2+ concentration must be reached to induce this differential Ca2+ rise by releasing Ca2+ from an intranuclear Ca2+ store. PMID- 1443107 TI - Membrane currents in a calcitonin-secreting human C cell line. AB - The whole cell version of the patch-clamp technique was used to identify and characterize voltage-gated Ca2+, Na+, and K+ currents in the calcitonin-secreting human thyroid TT cell line. Ca2+ current consisted of a single low-voltage activated rapidly inactivating component. The current was one-half maximally activated at a potential of -27 mV, while steady-state voltage-dependent inactivation was one-half complete at -51 mV. The Ca2+ current inactivated with a voltage-dependent time constant that reached a minimum of 16 ms at potentials positive to -15 mV. Deactivation kinetics could also be fit with a single voltage dependent time constant of approximately 2 ms at -80 mV. Replacing Ca2+ with Ba2+ reduced the maximum current by 18 +/- 5% (n = 6). The dihydropyridine Ca2+ agonist (-)BAY K 8644 did not affect the Ca2+ current, but 50 microM Ni2+ reduced it by 81 +/- 0.8% (n = 5). TT cells also possessed tetrodotoxin-sensitive voltage gated Na+ channels and tetraethylammonium-sensitive delayed rectifier type K+ currents. These results indicate that TT cells possess membrane currents necessary for the generation of action potentials. T-type Ca2+ channels are the sole pathway for voltage-dependent Ca2+ entry into these cells and may couple electrical activity to calcitonin secretion. PMID- 1443108 TI - Effect of cytochalasin D on the actin cytoskeleton of the toad bladder epithelial cell. AB - Cytochalasins are widely used to determine the role of actin in cellular processes. Their actions include capping of the barbed end of actin filaments as well as dimer formation, nucleation, and polymerization. We determined the effect of cytochalasin D (CD) on F-actin in the toad urinary bladder, an epithelium in which vasopressin depolymerizes F-actin. At a low concentration (0.25 microM), CD depolymerized F-actin in the unstimulated cell; at higher concentrations, there was a progressive reduction of depolymerization until actual polymerization was seen. Vasopressin plus CD produced no greater depolymerization than vasopressin alone, suggesting that CD and vasopressin act to a large extent on the same pool of F-actin. CD plus vasopressin also enhanced the fusion rate of aggrephores compared with vasopressin alone, indicating that intact actin filaments retard aggrephore fusion. Despite the increase in aggrephore fusion, water flow was not enhanced by CD, confirming previous reports that intact actin filaments are required for water channel emergence or stabilization in the apical membrane. Vasopressin plus 1 microM CD produced a striking increase in microvillar length, direct evidence of the polymerizing action of CD in the cell. PMID- 1443109 TI - In vivo estimation of lactose hydrolysis in premature infants using a dual stable tracer technique. AB - To investigate their putative capacity for lactose digestion, primed continuous orogastric infusions of [1-13C]glucose and D-[1-13C]lactose were administered on consecutive days to five premature infants (30-31 wk gestation, 15-32 days of age), who were fed by orogastric infusions of human milk or formula. By monitoring the plateau isotopic enrichment of plasma glucose using isotopomers containing the entire derivatized glucose molecule or C-2 through C-6, we were able to distinguish label appearing in the peripheral circulation deriving from unmetabolized glucose from that arising from recycled or fermented glucose (or lactose). Isotopic enrichment of the C-1 of glucose, corrected for recycling, was then calculated during each tracer infusion, and the fraction of dietary lactose subjected to in vivo hydrolysis was estimated from these values and the respective tracer infusion rates, assuming similar absorptive and metabolic fates of labeled glucose arising from either tracer. This fraction averaged 1.02 +/- 0.16 (SD), suggesting that lactose digestion is efficient by 34-wk postconceptional age. PMID- 1443110 TI - Heated dorsal hand vein sampling for metabolic studies: a reappraisal. AB - The purpose of the current study was to determine the accuracy of a given heated dorsal hand vein (HDHV) measurement in predicting a simultaneous arterial measurement and to validate this technique for use in stable isotope studies. Twenty catheterizations of the femoral artery, femoral vein, and a dorsal hand vein were performed in 13 healthy male subjects. Simultaneous blood samples were obtained from all three sites during primed continuous infusions of L-[1 13C]leucine (Leu) and L-[ring-2H5]phenylalanine (Phe) in the postabsorptive state, with or without intravenous glucose infusion. Relationships were examined by linear regression analysis, with 95% prediction intervals for femoral arterial values determined using the HDHV-derived values as independent variable. Glucose concentrations and isotopic enrichments of ketoisocaproate (KIC), Leu, and Phe were similar in HDHV- and arterial-derived blood, with slopes between 0.9414 and 1.0008, intercepts not different from zero, and r2 values of 0.7613 or greater (P < 0.05). Intercepts for KIC, Leu, and Phe concentrations all were different from zero (P < 0.05), and slopes ranged between 0.7560 and 0.8625. For each analysis the HDHV sample correlated better with the femoral arterial sample than with the femoral venous sample. These data support the use of HDHV sampling as a surrogate for direct arterial sampling but document significant limitations in the technique. PMID- 1443111 TI - Muscle glucose transport, GLUT-4 content, and degree of exercise training in obese Zucker rats. AB - The effects of high (HI)- and low (LI)-intensity exercise training were examined on insulin-stimulated 3-O-methyl-D-glucose (3-MG) transport and concentration of insulin-regulatable glucose transporter protein (GLUT-4) in the red (fast-twitch oxidative) and white (fast-twitch glycolytic) quadriceps of the obese Zucker rat. Sedentary obese (SED) and lean (LN) Zucker rats were used as controls. 3-MG transport was determined during hindlimb perfusion in the presence of 8 mM 3-MG, 2 mM mannitol, 0.3 mM pyruvate, and 0.5 mU/ml insulin. HI and LI rats displayed greater rates of red quadriceps 3-MG transport and GLUT-4 concentrations than SED rats. No significant differences in rates of 3-MG transport or GLUT-4 concentrations were observed in the red quadriceps of HI and LI rats. There were no differences found in the rates of 3-MG transport in the white quadriceps of HI, LI, and SED rats although the difference between the HI and SED rats approached significance (P < 0.07). The GLUT-4 concentration and citrate synthase activity of HI rats were significantly greater than SED rats. The 3-MG transport rates of LN rats were twofold greater than SED rats regardless of fiber type, but a difference in GLUT-4 content between the LN and SED rats was observed only in the white quadriceps. GLUT-4 content of the obese rats was significantly correlated with citrate synthase activity (r = 0.93) and 3-MG transport (r = 0.82).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443112 TI - Sites of infusion and sampling for measurement of rates of production in steady state. AB - When labeled and unlabeled (endogenously produced) substances enter an organism through different ports of entry, the anatomical location of these entry sites must be taken into account explicitly in calculating rates of appearance. All traditional formulas that are used for calculating rates of appearance are based on the assumption that labeled and unlabeled substances enter by means of the same port. These formulas are, therefore, not in general valid for metabolites such as lactate, where the entry ports differ. In such cases, specific activity will not be uniform throughout the organism even when the labeled and unlabeled substances are both in steady state. One cannot speak of the (unique) specific activity, because none exists. It is useful in these cases to define a distributed specific activity, which is the ratio of the concentration of labeled substance at one anatomical site to the concentration of unlabeled substance at another. We can then show that the rate of appearance for the double steady state (steady tracer infusion method) is given, approximately, as the ratio of the rate of infusion of the labeled substance to a particular distributed specific activity. PMID- 1443113 TI - Suppression of central noradrenergic neuronal activity inhibits hyperglycemia. AB - Hypothalamic noradrenergic neuronal activity (NNA) and hepatic glucose output are stimulated by stress. The aim of the present investigation was to examine whether the blockade of noradrenergic responses to stress might suppress the associated hyperglycemia. Mass spectrometry was used for analysis of norepinephrine (NE) and its neuronal metabolite 3,4-dihydroxyphenylglycol (DHPG) in rat hypothalamus, and the ratio DHPG/NE was used as an index of NNA. Treatment of rats with 2-deoxy-D glucose (500 mg/kg ip, -30 min), yohimbine (10 mg/kg ip, -20 min), or neostigmine (2 micrograms icv, -60 min) increased both NNA and serum glucose (P < 0.05). When rats were additionally pretreated with pentobarbital (60 mg/kg ip; -60 min), the NNA responses were blocked (P < 0.01). At the same time the hyperglycemic responses were also inhibited (P < 0.01). In rats that had reduced NNA due to 7 days "gentling," serum glucose levels were also significantly reduced (P < 0.001) compared with naive controls. The data demonstrate that inhibition of central noradrenergic activity is also associated with an inhibition of hyperglycemia, raising the concept that therapies aimed at reducing central NNA may have a role in the management of diseases with excessive hepatic glucose output such as non insulin-dependent diabetes mellitus. PMID- 1443114 TI - Selective expression of an arachidonate 12-lipoxygenase by pancreatic islet beta cells. AB - The immunohistochemical distribution of arachidonate lipoxygenases in rat pancreas was characterized with specific polyclonal anti-5-lipoxygenase and anti 12-lipoxygenase antibodies. Immunohistochemical analysis of formaldehyde-fixed paraffin-embedded rat pancreas using anti-12-lipoxygenase antibody and biotin avidin-peroxidase detection demonstrated specific staining of islets and no staining of pancreatic exocrine tissue. Less intense staining of pancreatic vascular myocytes and endothelial cells was also observed. Immunoblotting of isolated pancreatic islet extracts with the anti-12-lipoxygenase antibody demonstrated immunoperoxidase staining of a single protein band which comigrated with purified 12-lipoxygenase (relative molecular weight = 72,000) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Dispersed cells prepared from isolated islets and then subjected to fluorescence-activated cell sorting and immunostaining exhibited 12-lipoxygenase antigen in beta-cell populations but not in non-beta-cell (predominantly alpha-cell) populations. Assays of enzymatic activity confirmed that the 12-lipoxygenase-catalyzed conversion of arachidonic acid to 12-hydroxyeicosatetraenoic acid methyl ester occurred only with purified beta-cells and not with islet non-beta-cells. No evidence of 5-lipoxygenase antigen or enzymatic activity was found in purified beta-cells or in islet non-beta-cells. We conclude that rat pancreatic islet beta cells contain an arachidonate 12-lipoxygenase which shares antigenic epitopes with the homologous enzyme contained in tissues from other species. In addition, the selective localization of the 12-lipoxygenase to pancreatic beta-cells and its absence in pancreatic acinar cells and in islet non-beta-cells support observations suggesting that 12-lipoxygenase products may participate in glucose induced insulin secretion from beta-cells. PMID- 1443115 TI - Glucose kinetics following administration of an intravenous fat emulsion to low birth-weight neonates. AB - To evaluate the mechanism(s) of the observed increase in plasma glucose concentration following the administration of an intravenous fat emulsion to the neonate, we measured glucose kinetics in eight low-birth-weight neonates by the prime constant rate infusion technique with D-[6,6-2H2]glucose at a rate of 0.22 +/- 0.01 mumol.kg-1 x min-1 (39.4 +/- 1.3 micrograms.kg-1 x min-1) while the neonates received 32 +/- 5 mumol.kg-1 x min-1 glucose (6.3 +/- 1.1 mg.kg-1 x min 1) plus an amino acid mixture (parenteral alimentation) alone and in combination with an intravenous fat emulsion (Intralipid). Following the latter combination, there were significant increases in plasma glucose concentration [4.07 +/- 0.11 (73 +/- 2 mg/dl) to 5.00 +/- 0.22 mmol/l (90 +/- 4 mg/dl); P < 0.01] and in plasma insulin concentration [72 +/- 14 (10 +/- 2 microU/ml) to 172 +/- 36 pmol/l (24 +/- 5 microU/ml); P < 0.05]. The parenteral alimentation and intravenous fat effusion combination did not affect the glucose production rate: 0.15 +/- 0.05 mumol.kg-1 x min-1 (0.03 +/- 0.01 mg.kg-1 x min-1) during the parenteral alimentation alone and 0.16 +/- 0.05 mumol.kg-1 x min-1 (0.03 +/- 0.01 mg.kg-1 x min-1) when parenteral alimentation was combined with an intravenous fat emulsion. We conclude that the increased plasma glucose concentration seen in association with administration of parenteral alimentation combined with an intravenous fat emulsion to the premature neonate is not due to enhanced glucose production but could be the result of alterations in glucose utilization. PMID- 1443116 TI - Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue. AB - Whole body energy expenditure, thermogenic and metabolic changes in the forearm, and intercellular glucose concentrations in subcutaneous adipose tissue on the abdomen determined by microdialysis were measured during epinephrine infusion in healthy subjects. After a control period, epinephrine was infused at rates of 0.2 and 0.4 nmol.kg-1 x min-1. Whole body resting energy expenditure was 4.36 +/- 0.56 (SD) kJ/min. Energy expenditure increased to 5.14 +/- 0.74 and 5.46 +/- 0.79 kJ/min, respectively (P < 0.001), during the epinephrine infusions. Respiratory exchange ratio was 0.80 +/- 0.04 in the resting state and did not change. Local forearm oxygen uptake was 3.9 +/- 1.3 mumol.100 g-1 x min-1 in the basal period. During epinephrine infusion, it increased to 5.8 +/- 2.1 (P < 0.03) and 7.5 +/- 2.3 mumol.100 g-1 x min-1 (P < 0.001). Local forearm glucose uptake was 0.160 +/- 0.105 mumol.100 g-1 x min-1 and increased to 0.586 +/- 0.445 and 0.760 +/- 0.534 mumol.100 g-1 x min-1 (P < 0.025). The intercellular glucose concentration in the subcutaneous adipose tissue on the abdomen was equal to the arterial concentration in the basal period but did not increase as much during infusion of epinephrine, indicating glucose uptake in adipose tissue in this condition. If it is assumed that forearm skeletal muscle is representative for the average skeletal muscle, it can be calculated that on average 40% of the enhanced whole body oxygen uptake induced by infusion of epinephrine is taking place in skeletal muscle. It is proposed that adipose tissue may contribute to epinephrine-induced thermogenesis. PMID- 1443117 TI - Effects of streptozotocin-induced diabetes on rough endoplasmic reticulum and lysosomes of rat liver. AB - In the absence of amino acids and insulin, ribosome-free regions of the rough endoplasmic reticulum (RER) invaginate to form an autophagosome, which matures into an autolysosome (W. A. Dunn, Jr., J. Cell Biol. 110: 1923-1933, 1990). In this study, biochemical and morphological methods were used to examine the structure and integrity of the RER and the lysosome-vacuolar system in livers of untreated (normal serum insulin) and streptozotocin (STZ)-treated (depressed serum insulin) fed and fasted rats. Degradation of endogenous proteins was increased by 70% in STZ-treated animals. Proteolysis was further enhanced when these animals were deprived of food for 24 h. These alterations in protein turnover were accompanied by increases in the fractional volume of autophagic vacuoles and in the hepatic amounts of three lysosomal hydrolases. These effects of STZ were prevented on administration of insulin. In addition, there was an insulin-dependent 50% loss of RER surface area in livers from STZ-treated rats. This loss of structural RER was accompanied by comparable decreases in the cellular amounts of two RER membrane proteins and one luminal protein, suggesting that the RER was degraded as a unit. Additional losses of RER were observed when STZ-treated rats were fasted. Furthermore, the hepatic amounts of two serum proteins decreased, suggesting the functional capacity of the RER was reduced. Combined, the data suggest that in STZ-induced diabetes the losses in RER are related to enhanced autophagy. PMID- 1443118 TI - Reciprocal feedback regulation of kidney angiotensinogen and renin mRNA expressions by angiotensin II. AB - The present study asks whether angiotensin II (ANG II), a potent inhibitor of renal renin synthesis and release, regulates renal angiotensinogen synthesis. ANG II (or vehicle) was intravenously infused into male Sprague-Dawley rats for 3 days (vehicle or 100, 300, and 1,000 ng.kg-1 x min-1, n = 8/group), significantly increasing mean plasma ANG II concentrations and raising mean arterial blood pressure (MAP). ANG II dose dependently suppressed plasma renin concentration, kidney renin concentration, and renal renin mRNA levels. In contrast, ANG II infusion increased renal angiotensinogen mRNA levels stepwise to 122, 136 (P < 0.05), and 150% (P < 0.05) of control and also increased both liver mRNA levels (P < 0.05) and plasma angiotensinogen concentration (P < 0.05). Three days of angiotensin-converting enzyme inhibition (10 mg.kg-1 x day-1 quinapril in drinking water, n = 8) significantly decreased MAP (P < 0.05) and increased both mean plasma renin concentration (P < 0.05) and renal renin mRNA levels (P < 0.005). Plasma ANG II concentration tended to decrease (not significant), and neither renal nor hepatic angiotensinogen mRNA levels displayed significant difference. However, when data from ANG II-infused and quinapril-treated rats were analyzed together, correlation between plasma ANG II concentrations and renal angiotensinogen mRNA levels was highly significant (P < 0.005, r = 0.585). Thus plasma ANG II upregulates renal angiotensinogen gene expression and downregulates renal renin gene expression, a reciprocal feedback regulation that may have important physiological consequences. PMID- 1443119 TI - Pharmacokinetics of ANF and urodilatin during cANF receptor blockade and neutral endopeptidase inhibition. AB - Urodilatin is a new member of the family of natriuretic peptides. It is of renal origin. Previous reports indicate that urodilatin is natriuretic in lower doses than atrial natriuretic factor (ANF)-(99-126) and that it might be more effective than ANF in the treatment of cardiovascular edema. The present study was designed to compare the pharmacokinetics of the hydrolysis and clearance of 125I-labeled urodilatin and 125I-ANF. In control rats, the volume of distribution (Vss), metabolic clearance rate (MCR), and distribution half-life (distribution t1/2) of urodilatin in plasma were not significantly different from those of ANF. Infusion of clearance (c)ANF-(4-23), a specific ligand for receptors that clear ANF in excess amounts (i.e., a bolus injection of 100 micrograms/kg followed by a continuous infusion of 10 micrograms.kg-1 x min-1), increased the amount of intact peptide in the plasma to the same extent for both urodilatin and ANF. In addition, cANF-(4-23) decreased the Vss and the MCR and increased the distribution t1/2 of both peptides to about the same degree. Prior treatment of rats with SQ-28,603, a specific neutral endopeptidase (NEP; EN 3.4.24.11) inhibitor, was without significant effect on the metabolic clearance of urodilatin, whereas it decreased the clearance of ANF by 65%. Furthermore, an infusion of SQ-28,603 suppressed the appearance of the hydrolytic products of ANF in blood but not of urodilatin. Moreover, the inhibitor increased the total amount of ANF recovered in the kidneys to five times the control values, whereas it did not alter the renal uptake of urodilatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443120 TI - Fasting and postmeal phenylalanine metabolism in mild type 2 diabetes. AB - We have investigated postabsorptive and postprandial phenylalanine kinetics in non-obese type 2 diabetic patients [non-insulin-dependent diabetes mellitus (NIDDM)], using a double-isotope technique and the constant oral administration of a synthetic mixed meal. Fasting and postmeal glucose levels were increased (P < 0.01) in NIDDM (165 +/- 16 to 226 +/- 24 mg/dl), with respect to normal controls (85 +/- 3 to 102 +/- 6 mg/dl). Fasting insulin concentrations were comparable in NIDDM (13 +/- 2 microU/ml) and in normals (12 +/- 2 microU/ml), but after the meal it increased less (P < 0.07) in NIDDM vs. normals (to 36 +/- 5 vs. 56 +/- 12 microU/ml, respectively; P < 0.01 vs. basal for both). Postabsorptive phenylalanine rate of appearance (R(a)) in NIDDM (0.63 +/- 0.08 mumol.kg-1 x min 1) was comparable to that of controls (0.73 +/- 0.05 mumol.kg-1 x min-1, not significant). During the meal, total and endogenous phenylalanine R(a), splanchnic uptake, oxidation, and nonoxidative disposal of the ingested phenylalanine were also comparable in the two groups. These data indicate that fasting and postprandial kinetics of the essential amino acid phenylalanine are normal in NIDDM. PMID- 1443121 TI - Adrenergic regulation of type II 5'-deiodinase circadian rhythm in rat harderian gland. AB - This paper reports on the regulation of the nyctohemeral profile of type II thyroxine 5'-deiodinase (T45'D) activity in the rat harderian gland. Harderian gland T45'D activity exhibits a nighttime increase with maximal values late in the dark period (0200-0400 h) and basal values during the daytime. The nocturnal rise of the deiodinating activity was prevented by either exposure of animals to light at night, injecting the animals with both alpha- and beta-adrenergic receptor blockers, or bilateral superior cervical ganglionectomy (SCGx). However, adrenalectomy did not affet the enzyme activity in the harderian gland. In brown adipose tissue (BAT), where thyroid hormone metabolism is extremely dependent on alpha 1-adrenergic stimulation by blood-circulating catecholamines, adrenalectomy significantly decreased T45'D activity. Deiodinating activities in brain frontal cortex (BFC) and pituitary gland were unaffected by adrenalectomy. Unlike in the harderian gland, SCGx did not modify the T45'D activity in either BAT, BFC, or the pituitary gland. The results suggest that elevated plasma catecholamines are not required for harderian gland T45'D activation and that the nyctohemeral profile of the enzyme activity in the harderian gland is dependent on the noradrenergic input from the superior cervical ganglia. PMID- 1443122 TI - Glucose-induced insulin release in islets of young rats: time-dependent potentiation and effects of 2-bromostearate. AB - The development of glucose-stimulated insulin release and time-dependent potentiation (TDP) has been studied in isolated islets from 7-, 14-, and 21-day old and 3-mo-old rats. Responses were small at 7 days and changed little at 14 days. At 21 days the amount of insulin released in response to glucose was two times that at 14 days but was still less than one-half that released by 3-mo islets. Glucose-induced TDP was absent at 7 days but was present at 21 days. The second phase response to glucose decreased with perifusion time in 7-, 14-, and 21-day islets. In 7- and 21-day islets, high glucose in the presence of 2 bromostearate, an inhibitor of fatty acid oxidation, prevented the time-dependent decrease in responses; in addition, it induced TDP and enhanced TDP in the 7-day and 21-day islets, respectively. The data suggest that, in the young islet, glucose metabolism fails to inhibit fatty acid oxidation as it does in the mature islet and that this leads to a diminished signal for stimulus-secretion coupling. PMID- 1443123 TI - Inhibition of hepatic ketogenesis by tumor necrosis factor-alpha in rats. AB - Tumor necrosis factor-alpha (TNF-alpha) stimulates hepatic lipogenesis. Therefore, it could play a role in the control of ketogenesis. To test this hypothesis, we measured simultaneously free fatty acids (FFA; [1-13C]palmitate) and ketone body (KB; [3,4-13C2]acetoacetate) kinetics, before and after intraperitoneal injection of saline or TNF-alpha, in postabsorptive rats or rats starved for 24 h. In both groups of rats, TNF-alpha injection did not modify insulinemia and induced a moderate increase of FFA concentrations and appearance rates (P < 0.05). Despite increased FFA availability, ketogenesis was impaired after TNF-alpha injection, as shown by lower KB concentrations and appearance rates; this effect was more important in postabsorptive than in starved rats. The percentage of FFA flux used for ketogenesis was decreased by TNF-alpha in the postabsorptive group (P < 0.05) and starved (P < 0.05) rats. In both groups, maximal liver acetyl-coenzyme A carboxylase activity and estimated phosphorylation state were not modified by TNF-alpha injection, but hepatic concentrations of citrate were increased (P < 0.05). This increased citrate level could be related to a mobilization of glucose stored as glycogen since liver glycogen was decreased by TNF-alpha injection (P < 0.05). In conclusion, TNF alpha injection in rats decreased hepatic ketogenesis. This action could be related to an increased mobilization and utilization of carbohydrate stores. PMID- 1443124 TI - Visceral fat accumulation in obese subjects: relation to energy expenditure and response to weight loss. AB - Seventy-eight healthy obese subjects, 40 premenopausal women and 38 men aged 27 51 yr received a 4.2 MJ/day energy-deficit diet for 13 wk. Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) were measured by indirect calorimetry. Abdominal subcutaneous and visceral fat areas were calculated from magnetic resonance imaging scans before and after weight loss. Before weight loss, visceral fat accumulation was positively correlated with higher levels of RMR (P < 0.05) and DIT (P < 0.01) in women but not in men. The mean weight reduction was 12.2 +/- 3.5 (SD) kg. In men but not in women, an initially large visceral fat depot was associated with a reduced loss of weight and total fat mass (P < 0.05). Within each sex, an initial abundance of visceral fat was significantly related to a larger loss of visceral fat (P < 0.001) and in men to a smaller loss of subcutaneous fat (P < 0.05). These results suggest that there may be gender differences in the associations between visceral fat accumulation and components of energy expenditure (RMR and DIT) in obese subjects. Obese subjects with an initial abundance of visceral fat do not lose more body weight but more visceral fat than subjects with less visceral fat. PMID- 1443125 TI - Early metabolic consequences of epidermal growth factor administration to neonatal rats. AB - Daily administration of epidermal growth factor (EGF) to neonatal rodents elicits a classic morphogenetic syndrome. In this study, we examined the early (minutes to hours) consequences of EGF treatment in the neonatal rat (age 0-72 h). Significant findings included a rapid reduction in resting heart rate 4 h after EGF treatment accompanied by a sensitive dose- and age-dependent decrease in systemic oxygen consumption (VO2). Midscapular skin temperature (MST) was measured as a putative noninvasive indicator of brown adipose tissue thermogenesis. As little as 10 ng EGF/g body wt elicited a significant reduction in MST. Both the decrease in VO2 evoked by EGF and the MST response were potentiated by environmental cold exposure. EGF treatment also resulted in rapid (90 min) reductions in circulating levels of glycerol, triglyceride, and cholesterol while increasing serum glucose and arachidonic acid. Other free fatty acids were unaffected. Serum lactate levels were increased by EGF with the same time course as the reduction in VO2. These results provide new biochemical data on the pharmacological actions of EGF and further characterize the EGF-treated neonatal rodent as an intriguing in vivo model of growth factor action. PMID- 1443126 TI - Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans. AB - Leucine has been proposed as an in vivo regulator of protein metabolism, although the evidence for this in humans remains inconclusive. To test this hypothesis, we infused either L-leucine (154 +/- 1 mumol.kg-1 x h-1) or saline intravenously in six healthy men in two separate studies. L-Leucine infusion increased plasma concentrations of leucine and alpha-ketoisocaproate from 112 +/- 6 and 38 +/- 3 mumol/l to 480 +/- 27 (P < 0.001) and 94 +/- 13 mumol/l (P < 0.001), respectively, without any significant change in circulating insulin or C peptide levels. Leucine infusion decreased plasma concentrations of several amino acids and decreased whole body valine flux and valine oxidation (using L-[1-13C]valine as a tracer) and phenylalanine flux (using [2H5]-phenylalanine as a tracer). According to arteriovenous differences across the leg, the net balance of phenylalanine, valine, and lysine shifted toward greater retention during leucine infusion, whereas alanine balance did not change. Valine release and phenylalanine release from the leg (estimated from the dilution of respective tracers) decreased, indicating inhibition of protein degradation by leucine infusion. We conclude that leucine decreases protein degradation in humans and that this decreased protein degradation during leucine infusion contributes to the decrease in plasma essential amino acids. This study suggests a potential role for leucine as a regulator of protein metabolism in humans. PMID- 1443127 TI - Hypertension and insulin resistance: role of sympathetic nervous system activity. AB - The purpose of this study was to test the hypothesis that heightened sympathetic nervous system (SNS) activity contributes to the mechanism by which hypertension is associated with insulin resistance in humans. We performed frequently sampled intravenous glucose tolerance tests to determine tissue sensitivity to metabolic effects of insulin (SI) and measured plasma norepinephrine (NE) levels in 21 normotensive and 14 hypertensive Caucasian subjects. Compared with the normotensive subjects, hypertensive subjects had decreased SI (5.4 +/- 0.5 vs. 4.0 +/- 0.7 x 10(-5) x min-1 x pM-1; P = 0.03) but similar plasma NE levels (normotensive: 1.82 +/- 0.12 vs. hypertensive: 1.73 +/- 0.16 nM; P = 0.23). In a multiple regression model, only body mass index (BMI) and mean arterial blood pressure (MABP) were significant independent predictors of SI [SI = (-0.513)(BMI) + (-0.058)(MABP) + 23.6; r = 0.748; P = 0.0001]; age, plasma glucose, epinephrine, and NE level did not enter this model. As an additional test of this hypothesis, seven hypertensive subjects were restudied after 10 days of guanadrel therapy to determine whether SI would increase during suppression of SNS activity by guanadrel. Despite a significant reduction in plasma NE levels with guanadrel (baseline: 1.63 +/- 0.18 vs. guanadrel: 0.99 +/- 0.14 nM; P = 0.01), there was no significant change in SI (baseline: 2.97 +/- 0.78 vs. guanadrel: 2.41 +/- 0.54 x 10(-5).min-1 x pM-1; analysis of variance P = 0.57). We conclude that, in the Caucasian population we studied, heightened SNS activity is not essential for the insulin resistance observed in hypertensive humans. PMID- 1443128 TI - Endurance training does not enhance total energy expenditure in healthy elderly persons. AB - Physical exercise is prescribed to older individuals to increase cardiovascular fitness and improve body composition. However, there is limited information on the effect of exercise on total energy expenditure (TEE) and its components. We therefore determined the effects of short-term endurance training in 11 elderly volunteers (56-78 years) on changes in 1) TEE, from doubly labeled water; 2) resting metabolic rate (RMR), from respiratory gas analysis, 3) the energy expenditure of physical activity (EEPA), aside from that associated with the training program, and 4) body composition from a combination of body density with total body water. Endurance training increased maximum oxygen consumption (VO2max) by 9% (2.00 +/- 0.67 to 2.17 +/- 0.64 l/min; P < 0.05) and RMR by 11% (1,596 +/- 214 to 1,763 +/- 170 kcal/day; P < 0.01). There was no significant change in TEE (2,408 +/- 478 to 2,479 +/- 497 kcal/day) before and during the last 10 days of endurance training because of a 62% reduction in EEPA (571 +/- 386 to 340 +/- 452 kcal/day; P < 0.01). There was no change in body mass, but fat mass decreased (21.6 +/- 6.6 to 20.7 +/- 6.6 kg; P < 0.05). The increase in fat free mass (49.5 +/- 9.0 to 50.4 +/- 9.1 kg; P < 0.05) was explained by an increase in body water (35.9 +/- 6.5 to 36.8 +/- 6.3 kg; P < 0.05). We conclude that in healthy elderly persons, endurance training enhances cardiovascular fitness, but does not increase TEE because of a compensatory decline in physical activity during the remainder of the day. PMID- 1443129 TI - Precision and accuracy of doubly labeled water energy expenditure by multipoint and two-point methods. AB - Two-point or multipoint, that is the question. Equations are developed to compare the precision and accuracy of energy expenditure, as estimated from doubly labeled water data, when analyzed by the multipoint and two-point methods. The equations convert the enrichments of deuterium and oxygen-18 into their ratio and product, quantities that are less covariant than the two isotopes themselves are. This is important not only for estimating the precision but also as a graphical aid, since the ratios of the enrichments model carbon dioxide production, whereas the enrichment products largely model water turnover. Using data on 12 human subjects from the United Kingdom and The Gambia as examples, the combined precision and accuracy of the multipoint method (CV 3.6%) was found to be appreciably better than the two-point method (CV 5.4%). The bias in the multipoint estimate of body pool size would need to be three times as large as was observed before it canceled out the better precision. PMID- 1443130 TI - Membrane receptors for aldosterone: a novel pathway for mineralocorticoid action. AB - Rapid nongenomic in vitro effects of aldosterone on intracellular electrolytes, cell volume, and Na(+)-H+ antiport have been found in human mononuclear leukocytes (HML). Binding of 125I-labeled aldosterone to plasma membranes of HML shares important features with these functional data. This includes a very low apparent dissociation constant (Kd) of 0.1 nM for both aldosterone and the effect on the Na(+)-H(+)-antiport, a high turnover rate, and the almost exclusive binding selectivity for aldosterone. Dexamethasone, RU 26988, corticosterone, ouabain, amiloride, and 18-hydroxyprogesterone were inactive as ligands. Deoxycorticosterone acetate had an intermediate activity with an apparent Kd of 100 nM. These findings are the first to demonstrate membrane binding of aldosterone being compatible with major aspects of its nongenomic effects. PMID- 1443131 TI - Influence of growth hormone on glucose-glucose 6-phosphate cycle and insulin action in normal humans. AB - Increased activity of the hepatic glucose-glucose 6-phosphate (G/G-6-P) cycle is associated with hepatic and peripheral insulin resistance in acromegaly. To determine whether a similar association occurs after short-term growth hormone (GH) elevation within the physiological range, two-step euglycemic hyperinsulinemic clamps were performed in normal human males after 12-h GH (2.2 ng.kg-1 x h-1) and control infusions. G/G-6-P cycle activity and endogenous glucose production (EGP) were determined by [2-3H]- and [6-3H]-glucose using labeled exogenous glucose infusions and selective enzymatic detritiation. GH increased levels of circulating lipid intermediates despite a twofold increase in basal insulin (P < 0.005), but plasma glucose, EGP, and G/G-6-P cycle activity were unchanged. GH impaired insulin suppression of EGP and lipid intermediates and impaired insulin stimulation of glucose disposal, but G/G-6-P cycle activity was unchanged. We conclude that increased activity of the G/G-6-P cycle does not contribute to the hepatic insulin resistance induced by GH under these conditions but that changes in fatty acid metabolism may be partly responsible for the impairment in hepatic and peripheral insulin action. PMID- 1443132 TI - Mass isotopomer distribution analysis: a technique for measuring biosynthesis and turnover of polymers. AB - Mass isotopomer distribution analysis (MIDA) is a technique for measuring biosynthesis and turnover of polymers in vivo. A stable isotopically enriched precursor is administered, and the relative abundances of different mass isotopomers in the polymer of interest are measured by mass spectrometry (MS). By comparison of statistical distributions predicted from the binomial or multinomial expansion to the pattern of excess isotopomer frequencies observed in the polymer, the enrichment of the biosynthetic precursor subunits (p) for newly synthesized polymers is calculated. MIDA thereby provides a solution to the problem of determining the isotope content in the actual precursor molecules that entered a particular polymeric product (the "true" precursor). The fraction of polymer molecules in a mixture that were newly synthesized during an isotopic experiment (fractional synthesis) can then be calculated. We describe some mathematical characteristics of MIDA and point out certain advantageous features. For example, mathematical estimates of p remain valid even if there does not exist a single anatomic or functional precursor pool. The interpretation of decay curves of endogenously labeled polymers may be improved by the use of higher mass isotopomers, which better fulfill the assumption of flash labeling. By combining fractional synthesis values with rate constants of decay, absolute endogenous synthesis rates can be calculated. Thus, by using probability logic combined with MS analysis, MIDA allows dynamic measurements to be made through analyses on a polymer alone during both isotopic incorporation and decay phases. The method has been applied to fatty acids, cholesterol, and glucose and is potentially applicable to nucleic acids, porphyrins, perhaps proteins, and many other classes of polymers. PMID- 1443133 TI - Role of platelet-activating factor in hepatic responses after bile duct ligation in rats. AB - Role of platelet-activating factor (PAF) as a potential mediator of hepatic pathophysiology was investigated using a rat model of obstructive jaundice. Over a 1-wk course of bile duct ligation, a sixfold increase in tissue levels of PAF (1.57 +/- 0.43 ng/g vs. control 0.24 +/- 0.08 ng/g) occurred in the liver, whereas no change was observed in PAF levels in plasma. Concomitantly, endotoxin was detected in portal blood drawn from jaundiced rats, and antagonism of the putative effect of endotoxin by neomycin plus polymyxin B reduced local PAF concentrations in livers from jaundiced animals. Induction of neutropenia failed to alter the elevated hepatic PAF concentrations. Moreover, a large quantity of PAF was released spontaneously from Kupffer cells isolated from livers derived from jaundiced rats but not from endothelial cells or hepatocytes from the same animals. An in vitro study using cultured Kupffer cells from normal rats indicated that Kupffer cells secreted a significant amount of PAF in response to lipopolysaccharide challenge; pretreatment of cells with polymyxin B prevented this stimulated PAF release. Treatment of animals with either of two PAF receptor antagonists (BN 52021 and WEB 2170) partially prevented the increase in tissue levels of eicosanoids and O2-derived free radicals and partially alleviated liver injury as judged by the appearance of glutamate-pyruvate transaminase in the plasma of jaundiced rats. The present study indicates 1) that endogenous PAF may be an important signaling mediator for the hepatic inflammatory alterations associated with short-term bile duct ligation and 2) that the interaction of Kupffer cells with portal endotoxin is the mechanism by which PAF is produced locally. PMID- 1443134 TI - Ontogenetic development of nutrient transporters in rat intestine. AB - We measured intestinal brush-border uptakes of three sugars and three amino acids, plus intestinal morphometric parameters, in rats from the day of birth until adulthood. Rates of body weight gain had pronounced peaks in the suckling phase and again during weaning, separated by a dip at the onset of weaning. These two peaks coincided with peaks or plateaus in intestinal growth and in glucose (Glc) and proline (Pro) uptake capacities, which may provide the basis for high rates of body growth. Pro uptake declined relative to Glc uptake upon weaning, reflecting decreasing protein needs for growth and decreasing protein intake relative to carbohydrate intake. Fructose (Frc) and lysine uptake increased steeply on weaning, whereas galactose uptake declined relative to that of Glc. Rats prevented from normal weaning by being maintained on dry milk were generally similar to normal rats weaned onto chow. Notably, their Frc uptake still rose steeply on weaning despite low dietary Frc levels, suggesting hard-wired regulation of Frc transporter development. Our in vitro uptakes are similar to modern in vivo values in the same strain of rats. Nutrient uptake capacities exceed normal dietary intakes by only a modest safety margin. PMID- 1443135 TI - Ontogenetic development of nutrient transporters in cat intestine. AB - Cats are unusual among mammals in several features of nutritional ontogeny related to their strict carnivory as adults. Hence we measured intestinal brush border uptakes of three sugars and six amino acids, plus intestinal morphometric parameters, in cats from birth until after weaning. The ratio of amino acid to sugar uptake increases with age, in parallel with the increasing protein/carbohydrate ratio of the natural diet. At weaning, when galactose disappears from the natural diet of cats, the galactose/glucose uptake ratio declines steeply, implying a developmental sequence of multiple aldohexose transporters. Fructose uptake remains low at all ages. Uptakes of arginine (hyperessential to cats) and of lysine are notably high throughout the suckling period. The intense perinatal intestinal hyperplasia observed in many other mammal species is absent in cats. The developmental course of intestinal uptake capacities normalized to metabolic live mass parallels the course of relative body growth rates. The "safety margin" of uptake capacity over intake is greater for essential than nonessential amino acids and is greatest for the hyperessential arginine. PMID- 1443136 TI - Glutathione as a primary osmotic driving force in hepatic bile formation. AB - Indirect evidence suggests that transport of glutathione (GSH) across the canalicular plasma membrane into bile contributes to the formation of the bile acid-independent fraction of bile flow. To directly test this hypothesis, the present study measured bile flow in isolated perfused rat livers whose biliary GSH excretion rate was selectively modulated by administration of GSH monoethyl ester (50, 100, and 200 mumol infused over a 20-min interval), a high dose of GSH itself (550 mumol over 20 min), and the three amino acid components of GSH (70 mumol each) with and without methionine (35 mumol). Animals were starved overnight to decrease hepatic GSH levels, and livers were pretreated with acivicin to inhibit gamma-glutamyl transferase. Livers perfused single pass with Krebs-Henseleit buffer excreted bile acids at a relatively low rate of 1-3 nmol.min-1 x g-1, and this rate was unaffected by agents used to alter biliary GSH efflux. In comparison, basal biliary GSH efflux rates were 8-13 nmol.min-1 x g-1. Administration of the GSH ester produced a dramatic dose-dependent choleresis, a stimulation of biliary GSH excretion, and resulted in the biliary excretion of intact GSH ester. Changes in total biliary GSH excretion and bile flow were temporally and quantitatively related. Infusion of GSH and amino acid supplementation also resulted in higher rates of bile flow and biliary GSH excretion, but their effects were more modest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443137 TI - Constitutive expression of the taurine transporter in a human colon carcinoma cell line. AB - The human colon carcinoma cell line HT-29, when grown to confluence, was found to take up taurine and accumulate it against a concentration gradient from a NaCl containing uptake medium. Replacement of NaCl with choline chloride almost totally abolished the uptake. Taurine uptake was dependent not only on Na+ but also on Cl-, because other anions failed to support the uptake in the presence of Na+. The uptake process was specific for beta-amino acids such as taurine, hypotaurine, and beta-alanine. Apparently, a single transport system with a Michaelis-Menten constant of 10.6 +/- 0.3 microM was responsible for the uptake. Stoichiometric analyses revealed that the Na+:taurine coupling ratio was 2:1, whereas the Cl-:taurine coupling ratio was 1:1. Culture of the cells in the presence of taurine caused downregulation of the uptake system. These cells were also capable of accumulating beta-alanine against a concentration gradient in the presence of NaCl. Beta-Alanine uptake occurred via a single transport system with an apparent Michaelis-Menten constant of 36 +/- 2 microM. Taurine and beta alanine exhibited mutual interaction during uptake. Kinetic experiments strongly suggested that a common transporter was responsible for the uptake of these two beta-amino acids. It is concluded that the HT-29 cells constitutively express the taurine transporter and that this cell line may be a suitable model for investigations of intestinal taurine transporter. PMID- 1443138 TI - Histamine potentiation by hydroxylamines: structure-activity relations; inhibition of diamine oxidase. AB - Hydroxylamines potentiated the responses of the canine colonic epithelium to histamine but not to other agonists such as serotonin or carbachol. We tested the hypothesis that an inhibition of histamine catabolism could explain the observed potentiation. A clear structure activity relation was defined, active compounds having the structure NH2-O-R, R being a simple uncharged aliphatic group. Active compounds delayed the disappearance of histamine from the bathing solutions and inhibited colonic diamine oxidase, an effect mimicked by standard inhibitors aminoguanidine and semicarbazide. Histamine agonists that possessed an imidazole nucleus (2- and 4-methylhistamine) were affected, whereas impromidine, 2 pyridylethylamine, and dimaprit were not. Agonist specificity combined with the enzyme data suggest an inhibition of histamine catabolism as a possible mechanism for the potentiating effects observed. PMID- 1443139 TI - Importance of the liver in plasma clearance of hepatocyte growth factors in rats. AB - After intravenous administration of 125I-labeled hepatocyte growth factor (HGF), trichloroacetic acid-precipitable radioactivity in the plasma disappeared rapidly with an early phase half-life of 4 min. The amounts of 125I-HGF distributed to the liver, adrenal, spleen, kidney, and lung tissues were much greater than those that could be accounted for by distribution to the extracellular space alone. The first-pass removal of 125I-HGF by the liver was approximately 26%; the liver accounted for approximately 70% of early-phase removal. The hepatic handling was also analyzed using a single-pass perfused liver system. The steady-state extraction ratio of tracer 125I-HGF was 0.48 but dropped to 0.23 in the presence of excess HGF (135 pM), demonstrating hepatic removal saturation of HGF. In the presence of excess HGF, the heparin-washable 125I-HGF, the heparin-resistant and acid-washable 125I-HGF, and the internalized 125I-HGF dropped to 54, 31, and 32% of the control values. The presence of at least two binding sites for HGF on the liver cell surfaces was made clear: the heparin-washable site and the heparin resistant and acid-washable binding site, considered to have higher affinity for HGF. The internalization of 125I-HGF was observed to some extent even in the presence of excess HGF and phenylarsine oxide, known to be an inhibitor of polypeptides receptor-mediated endocytosis, suggesting the contribution of a relatively nonspecific internalization mechanism as well as receptor-mediated endocytosis. PMID- 1443140 TI - Intestinal absorption and lymphatic transport of peroxidized lipids in rats: effect of exogenous GSH. AB - We previously found that mucosal glutathione (GSH) plays an important role in the intestinal metabolism of luminal peroxidized lipids [T. Y. Aw, M. W. Williams, and L. Gray. Am. J. Physiol. 262 (Gastrointest. Liver Physiol. 25): G99-G106, 1992]. To determine the effects of exogenous GSH on lipid hydroperoxide elimination under conditions in which mucosal GSH was initially depleted with buthionine sulfoximine (BSO), we infused peroxidized lipid solutions without or with GSH into the proximal intestine of rats and monitored the steady-state output of hydroperoxides in lymph and recovery of luminal hydroperoxides. GSH supplementation in BSO-treated rats resulted in a concentration-dependent attenuation of lymphatic output of peroxidized lipids that was correlated with increases in mucosal GSH. Compared with BSO control, the luminal lipid hydroperoxide contents were significantly lower in GSH-supplemented rats, consistent with enhanced elimination of peroxidized lipids by exogenous GSH. The effect of GSH was ameliorated by the inhibitors of GSH uptake, suggesting that the uptake of GSH is required for promotion of intestinal removal of luminal hydroperoxides. Other thiols, either at comparable or higher concentrations than GSH, were without significant effects on lymphatic transport or luminal recovery of lipid hydroperoxides, indicating that these thiols are poor substitutes for GSH. Overall, the data are consistent with exogenous GSH being a source for cellular reduction of peroxidized lipids. Results from these studies could directly impact on future consideration of therapeutic means to increase cellular antioxidant systems to promote intestinal hydroperoxide detoxication. PMID- 1443141 TI - Symptomatic responses to stimulation of sensory pathways in the jejunum. AB - We hypothesized that intestinal afferent pathways inducing perception may be selectively activated by transmucosal electrical nerve stimulation, without disruption of the intrinsic myoelectrical rhythm. Hence, in 12 healthy subjects we measured perception (by a questionnaire) and jejunal slow wave activity (by electromyography), and we randomly applied for 1 min at 5-min intervals graded electrical (15 Hz, 100 microseconds) and mechanical stimuli (balloon distension) in the jejunum up to the respective discomfort threshold. Electrical and mechanical stimuli induced dose-related perception; the perception and discomfort thresholds were 39 +/- 7 and 63 +/- 6 mA and 31 +/- 3 and 49 +/- 5 ml for electrical and mechanical stimuli, respectively. More than one-half of electrical stimuli elicited clinical-type symptoms (abdominal pressure, fullness, colicky or sharp sensation) similar to those induced by mechanical stimuli; the remaining electrical stimuli (38 +/- 10%) induced paresthesia or flutterlike sensation. Similar types of symptoms were perceived with weak and strong stimuli. Jejunal slow wave activity (11.3 +/- 0.4 cycles/min) was not modified by either stimuli. We conclude that activation of intestinal sensory pathways, either by transmucosal nerve stimulation or via mechanoreceptors, induces a similar dose related symptomatic response, without interfering with the intrinsic myoelectrical activity. PMID- 1443142 TI - Sphincter of Oddi regulates flow by acting as a variable resistor to flow. AB - Two models of transsphincteric flow and a model evaluating pumping activity were established in the anesthetized Australian brush-tailed possum to determine whether the sphincter of Oddi (SO) acts as a resistor or as a pump. A simple model of transsphincteric flow (inflow only) demonstrated that at physiological common bile duct (CBD) pressure, 9.5 +/- 0.3 cmH2O (n = 7), transsphincteric flow occurred between SO pressure waves (n = 10). A second more complex transsphincteric flow model was established that permitted simultaneous measurements of inflow, outflow, CBD pressure, SO basal pressure, SO contraction frequency, and amplitude. At physiological CBD pressure, inflow always equaled outflow (157.0 +/- 11.2 and 156.4 +/- 11.4 microliters/min, respectively; n = 7). The SO displayed regular contractions superimposed on a basal pressure of 1.1 +/- 0.4 mmHg. Contraction amplitude was 12.6 +/- 3.0 mmHg and the frequency was 3.6 +/- 0.4 contractions/min (n = 7). Pressure waves recorded in the CBD corresponded to the SO contractions and reflected SO activity. Transsphincteric flow occurred between SO contractions and was obstructed by these contractions. Stimulation of SO activity (basal pressure and contraction frequency) with intra-arterial injections of motilin (200 ng/kg) or erythromycin (200 micrograms/kg) abolished transsphincteric flow. Reduction in SO contraction frequency to 72.7 +/- 7.2% (P < 0.01, paired t test) after administration of Cisapride (2 mg/kg iv) increased transsphincteric flow to 147.6 +/- 12.3% (n = 7, P < 0.05, paired t test). In six possums, possible SO pumping action was evaluated. A manometer was connected to the CBD, and a second manometer was connected to the duodenum surrounding the papilla.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443143 TI - Effect of increased tissue oxygen uptake on autoregulation in postnatal intestine. AB - To determine whether the rate of tissue oxygen utilization affects pressure-flow autoregulation in an age-dependent fashion in postnatal swine intestine, in vitro gut loops from 3- and 35-day-old swine were subjected to a 35% step reduction in arterial pressure under control conditions, during intra-arterial infusion of 2,4 dinitrophenol (DNP), and 30 min after luminal instillation of predigested artificial swine milk. Autoregulation was quantitated by determining the effect of pressure reduction on vascular resistance, and also by calculating Gf, a flow controlling gain factor that relates pressure and flow. DNP infusion increased oxygen uptake 77 and 58% in gut from 3- and 35-day-old swine, respectively, whereas feeding increased oxygen uptake approximately 50% in both groups. Under control conditions, arterial pressure reduction had no effect on vascular resistance in either group. During DNP infusion and 30 min after feeding, however, intestine from 35- but not from 3-day-old swine demonstrated significant vasodilation in response to pressure reduction. Gf averaged -0.06 +/- 0.11 vs. 0.21 +/- 0.08 (P < 0.05) before vs. DNP infusion, and 0.06 +/- 0.03 vs. 0.22 +/- 0.06 (P < 0.05) before vs. 30 min after feeding in intestine from 35-day-old swine; these increases in Gf indicate that the intensity of the pressure-flow response increased during experimental treatments. In contrast, Gf averaged -0.11 +/- 0.07 vs. -0.23 +/- 0.08 before vs. DNP infusion, and -0.23 +/- 0.06 vs. -0.23 +/- 0.09 before vs. 30 min after feeding in intestine from 3-day-old swine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443144 TI - Structural requirements of peptide YY for biological activity at enteric sites. AB - Peptide YY (PYY) is a colonic hormone consisting of 36 amino acids that is a potent inhibitor of pancreatic exocrine, gastric acid, and insulin secretion. The objective of the present experiments was to characterize the structural requirements of PYY for inhibition of pancreatic exocrine, gastric acid, and insulin secretion, using conscious dogs prepared with gastric and pancreatic fistulas. Intravenous administration of PYY-(1-36), PYY-(3-36), or PYY-(4-36) (400 pmol.kg-1 x h-1) inhibited cholecystokinin-8-stimulated (25 pmol.kg-1 x h-1) pancreatic exocrine secretion (P < 0.05); however, PYY-(1-10), PYY-(1-20), PYY-(6 36), PYY-(10-36), PYY-(13-36), PYY-(24-36), and PYY-(27-36) did not inhibit pancreatic exocrine secretion. Intravenous administration of PYY-(1-36), PYY-(3 36), or PYY-(4-36) (200, 400, 800 pmol.kg-1 x h-1) inhibited pentagastrin (0.5 microgram.kg-1 x h-1)-stimulated gastric acid secretion (P < 0.05), as well as 2 deoxy-D-glucose-stimulated insulin release (75 mg/kg) in a dose-related manner. PYY-(6-36), PYY-(13-36), and [Leu31, Pro34] neuropeptide Y did not inhibit either gastric acid secretion or insulin release. In the gastric acid and insulin secretion bioassays, PYY-(1-36) was significantly more potent than PYY-(3-36) and PYY-(4-36); however, in the pancreatic exocrine secretion bioassay, the inhibitory effects of PYY-(3-36) and PYY-(1-36) did not differ significantly. PYY (4-36) was less potent than PYY-(1-36) on pancreatic exocrine secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443145 TI - Passive autoregulation of portal venous pressure: distensible hepatic resistance. AB - Hepatic resistance to portal blood flow is extremely low and both the pre- and postsinusoidal resistance sites are distensible. Both isolated in situ and in vivo vascular circuitry were used in cats to demonstrate the principle of distensible resistance as a mechanism for the observation that blood flow was able to be decreased from 50 to 20 ml.min-1 x kg-1 while intrahepatic pressure decreased by only 1.4 +/- 0.2 mmHg and portal pressure by 2.0 +/- 0.4 mmHg. Presinusoidal resistance increased by 226% and hepatic venous resistance by 57%, thus accounting for passive autoregulation of portal pressure. The relation between vascular resistance and the distending blood pressure that acts on the resistance is predictable from the relationship IC = R.Pd3, where IC is the index of contractility (does not change passively, but does change with active vascular tone changes), R is vascular resistance (changes actively and passively), and Pd is distending blood pressure (estimated as the average of pressure on either side of the resistance vessels). The relatively minor effect of portal flow on portal pressure is accounted for by a combination of factors including the low basal resistance, the distensible resistance, the hepatic arterial buffer response, and hepatic blood volume compliance. By calculation of IC, the venous distensibility can be quantified and the passive effect of flow changes on portal and intrahepatic pressure determined. PMID- 1443146 TI - Electrophysiological identification of vagally innervated enteric neurons in guinea pig stomach. AB - Myenteric "command neurons" are thought to be the interface between extrinsic and intrinsic controls of gut functions and are thought to be responsible for transmission of vagal impulses to enteric microcircuits. To identify, electrophysiologically, myenteric neurons responding to electrical stimulation of the vagus, we developed an in vitro preparation of the gastric myenteric plexus in which the vagal innervation was preserved. The majority of myenteric neurons [102 of 155 (66%)] received fast excitatory postsynaptic potentials (fEPSPs) after stimulation of the vagus. The proportion of neurons receiving vagal input was highest at the lesser curve (98%) and decreased gradually when recordings were made from neurons located toward the greater curve. Only a small proportion of neurons (4 of 85 cells) showed a slow EPSP after a burst of vagal stimulation. No postsynaptic inhibitory potentials were observed. There was no preferential vagal input to either gastric I, gastric II, or gastric III neurons. The fEPSPs were due to the release of acetylcholine acting postsynaptically on nicotinic receptors. The behavior of the fEPSPs suggests multiple vagal inputs to a majority of myenteric neurons. Our observations call into question the concept of enteric command neurons in favor of a divergent vagal input with widespread modulatory influences over gastric enteric neurotransmission. PMID- 1443147 TI - Helicobacter pylori-associated ammonia production enhances neutrophil-dependent gastric mucosal cell injury. AB - The role of neutrophil and its chlorinated oxidant were investigated in Helicobacter pylori-induced gastric mucosal injury in vitro. Luminol-dependent chemiluminescence (ChL) was used to detect neutrophil-derived oxidants. ChL activity was significantly elevated when neutrophils were incubated in H. pylori, indicating that H. pylori actually elicits oxidative burst of neutrophils. To assess whether H. pylori-activated neutrophils exert the cytotoxicity for gastric mucosal cells, rabbit gastric mucosal cell was monolayered in culture wells and labeled with a fluorescence dye, 2',7'-bis(2-carboxyethyl)-5(6)carboxy fluorescein, which is retained in the intracellular space as long as the cell membrane is intact. Labeled cells were coincubated with neutrophils and H. pylori. We inferred from the cytotoxicity index (specific %cytotoxicity), which was calculated from fluorometrical measurements of supernatant and lysate, that the mucosal cells were significantly damaged by H. pylori-activated neutrophils. This injury was largely attenuated by eliminating urea from the incubation mixture or by acetohydroxamic acid, a potent urease inhibitor. Additionally, the scavengers of neutrophil-derived oxidants, including taurine, methionine, and catalase, also attenuated this injury. Cultured mucosal cells that were exposed to the solution containing monochloramine (an oxidant yielded by reaction of hypochlorous acid and ammonia) were highly damaged compared with cells exposed to hypochlorous acid or hydrogen peroxide at physiological concentrations. These data suggest that H. pylori-activated neutrophils promote gastric mucosal cell injury and that monochloramine plays a unique and important role in this process. PMID- 1443148 TI - A new method for quantitating intracellular transport: application to the thyroid hormone 3,5,3'-triiodothyronine. AB - After entering cells from plasma, molecules must permeate through the cytoplasm before they can be metabolized or excreted. If sufficiently slow, cytoplasmic transport may determine the overall rate of cellular elimination at steady state. Cytoplasmic transport of amphipathic molecules should be particularly slow because of extensive binding to intracellular membranes and proteins. Traditional transport models assume that molecules become instantly available for metabolism and canalicular excretion after entering the cell and thus cannot be used to assess cytoplasmic transport. We therefore extended the traditional multiple indicator dilution (MID) method of Goresky to explicitly incorporate cytoplasmic transport and used the resulting model to estimate the rate constant for cytoplasmic transport of the amphipathic thyroid hormone 3,5,3'-triiodothyronine (T3). We chose T3 because control studies indicated that it is neither metabolized nor excreted during the brief period of an MID experiment (40-90 s). The traditional MID model was unable to account for the data unless we postulated rapid metabolism or excretion of T3. In contrast, the new diffusion MID model fit the data closely without this false assumption and gave values for the influx and efflux rate constants that agreed with previously published data. The half-time for equilibration of T3 across the cytoplasm of the hepatocyte averaged 50 s. This corresponds to an effective cytoplasmic diffusion constant of 3.1 x 10(-8) cm2/s, which is > 100 times slower than expected for free T3 in water. Our results indicate that cytoplasmic transport of this model amphipathic compound is much slower than membrane transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443149 TI - Protein kinase C regulation of IEC-6 cell ornithine decarboxylase. AB - Experiments were performed to immunologically identify protein kinase C (PKC) in cultured IEC-6 cells. Polyclonal antibodies specific to PKC revealed an immunoreactive band of approximately 84 kDa in both cytosolic and solubilized particulate fractions. Treatment with phorbol 12-myristate 13-acetate (PMA; 10 nM x 60 min) increased the intensity of the 84-kDa band by 25% in the solubilized particulate fraction while decreasing it by 36% in the cytosolic fraction. Prolonged 24-h treatment with 300 nM PMA completely abolished the 84-kDa band in both fractions. Isoform-specific antisera demonstrated that alpha- and epsilon isoforms of PKC were expressed in IEC-6 cells. Treatment of quiescent cultures with PMA induced a maximal 400% increase in ornithine decarboxylase (ODC) activity. Similarly, addition of exogenous phospholipase C (PLC) to quiescent cells stimulated ODC activity. Downregulation of PKC with 300 nM PMA x 24 h inhibited basal, serum, and PLC-stimulated ODC activity by 70%. Northern analysis revealed that PKC downregulation was correlated with a marked reduction in ODC mRNA levels, suggesting regulation of ODC enzyme at this level. Despite their ability to modulate ODC activity in quiescent cultures, neither PMA nor PLC induced [3H]thymidine incorporation at 24 h. Furthermore, downregulation of PKC did not attenuate thymidine incorporation. However, chronic PMA treatment caused the cells to contact-inhibit at a 30% lower cell density, 3.16 x 10(6) vs. 2.1 x 10(6) cells/35-mm plate, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443150 TI - Coordination of deglutition and phases of respiration: effect of aging, tachypnea, bolus volume, and chronic obstructive pulmonary disease. AB - The effects of aging, tachypnea, bolus volume, and chronic obstructive pulmonary disease on the coordination of swallowing with the phases of respiration were studied by concurrent respirography and submental surface electromyography. Study findings showed that in young healthy volunteers, during rest, there is preferential coupling of subconscious swallowing with the expiratory phase of continuous respiration. This preferential coupling of swallowing with expiration was found to increase relative to other phases of respiration during water swallows and tachypnea (P < 0.05). Respiratory phase occurrence of swallowing and postdeglutitive resumption of respiration during exacerbation of chronic obstructive pulmonary disease was found to be significantly different compared with the basal state (P < 0.05). Respiratory phase occurrence of subconscious swallowing in the elderly was found to be different from the young (P < 0.05). Position had no significant effect on the coordination of swallowing and phases of respiration. We concluded that in resting young volunteers the majority of deglutitions are coupled with the expiratory phase of swallowing. This coupling is increased in frequency by the presence of a liquid bolus and tachypnea. And finally, age and chronic obstructive pulmonary disease alter this coordination significantly. PMID- 1443151 TI - Caco-2 cell transfection by rat intestinal alkaline phosphatase cDNA increases surfactant-like particles. AB - The rat enterocyte produces a particle with surfactant-like properties (including a whorled appearance, enrichment for dipalmitoyl phosphatidylcholine, and ability to lower surface tension) that also is enriched for intestinal alkaline phosphatase. Human Caco-2 cells grown on polycarbonate filters were utilized to study the secretion of these particles and exhibited whorls and strands of unilamellar membranes, particularly concentrated at the apical pole or near junctional complexes. Concentrated culture medium from these cells separated on continuous NaBr gradients revealed a fraction at density = 1.07 g/l enriched for phosphatidylcholine and intestinal alkaline phosphatase. This fraction contained membranous sheets containing alkaline phosphatase, detected by immunolocalization. Phosphatidylcholine comprised 54% of phospholipid in this fraction, compared with 20% in brush borders. When Caco-2 cells were transfected with cDNA encoding rat intestinal alkaline phosphatase, cellular phosphatase activity increased twofold, but activity in the medium increased 14-fold to > 200 (average 32)-fold. Ultrastructurally, compared with mock-transfected cells or cells transfected with human placental alkaline phosphatase, transfection with rat intestinal alkaline phosphatase cDNA led to intracellular and extracellular accumulation of surfactant-like particles. We conclude that surfactant-like particles are produced by Caco-2 cells, and their production can be enhanced by transfection with a cDNA encoding a protein known to be associated with such particles. PMID- 1443152 TI - Organic cation transport by rat liver plasma membrane vesicles: studies with tetraethylammonium. AB - Recently, an organic cation:H+ antiport was selectively identified on the sinusoidal domain of rat liver with the use of the endogenous organic cation N1 methylnicotinamide (NMN). Absence of NMN+:H+ exchange on canalicular membrane suggested that this transport process was primarily involved in organic cation uptake, leaving the mechanism(s) for organic cation secretion into bile unknown. To further define hepatic organic cation transport, we examined the characteristics of tetraethylammonium (TEA) transport in basolateral (blLPM) and canalicular (cLPM) rat liver plasma membrane vesicles. In cLPM vesicles, under voltage-clamped conditions, an outwardly directed H+ gradient stimulated [14C]TEA uptake compared with [14C]TEA uptake under pH-equilibrated conditions, consistent with electroneutral TEA:H+ exchange. The proton ionophore carbonyl cyanide p trifluoromethoxyphenylhydrazone had no effect on [14C]TEA uptake, demonstrating that pH-dependent [14C]TEA uptake was not the result of a H+ diffusion potential. In the absence of a pH gradient, the intravesicular presence of TEA trans stimulated uptake of [14C]TEA. Procainamide ethobromide (PAEB), vecuronium, and tributylmethylammonium (TBuMA), organic cations selectively excreted in bile, cis inhibited pH-dependent TEA uptake. In contrast, in blLPM vesicles, no pH gradient dependent [14C]TEA uptake was demonstrated. Instead, basolateral [14C]TEA uptake was significantly stimulated by a valinomycin-induced intravesicular-negative K+ diffusion potential. Basolateral [14C]TEA uptake was also cis-inhibited by PAEB, vecuronium, and TBuMA, but not by NMN. Conversely, PAEB, vecuronium, and TBuMA had no effect on basolateral pH-dependent [3H]NMN uptake. These findings suggest that organic cation transport, with TEA as a model quaternary amine, across the canalicular membrane is driven by an electroneutral organic cation:H+ exchange and that the transport of certain organic cations across the basolateral membrane is via a carrier-mediated system stimulated by an inside-negative membrane potential. PMID- 1443153 TI - Biomechanical properties of duodenal wall and duodenal tone during phase I and phase II of the MMC. AB - We used a new method, impedance planimetry, to look at variations in compliance, tone, and distension-induced peristaltic activity during phase I and phase II of the migrating myoelectric complex (MMC) in the human duodenum. A balloon was inflated stepwise with pressures up to 30 cmH2O in the duodenum, while the pressure and balloon cross-sectional area (CSA) were measured simultaneously. The biomechanical wall parameters were calculated from these measurements. Nine duodenal phase IIIs were recorded in six subjects. A balloon pressure of 20 cmH2O induced a smaller CSA in early phase I [266 (236-324) mm2] than in late phase II [385 (276-474) mm2] (P < 0.05). Balloon distensions elicited no contractions in phase I, whereas they increased contractile activity 60% (P < 0.05) proximal to the balloon and 4% distal to the balloon in late phase II. Step distensions in phase I with balloon pressures between 10 and 30 cmH2O increased the CSA from 40 (30-81) to 645 (603-704) mm2. It increased circumferential wall tension from 35 (28-63) to 429 (402-466) mm x cmH2O and the pressure elastic modulus from 9.7 (9.0-14.7) to 33.8 (27.6-33.8) cmH2O, respectively. Thus compliance differs from phase I to phase II. This is most likely caused by increased smooth muscle tone during phase I. Duodenal wall stiffness increases with the balloon pressure applied. PMID- 1443154 TI - Limitations of laser-Doppler velocimetry and reflectance spectrophotometry in estimating gastric mucosal blood flow. AB - This study investigated the accuracy of laser-Doppler flowmetry (LDV) and reflectance spectrophotometry (RS) measurements as an index of blood flow in the gastric mucosa of the rat, in experimental conditions such as pharmacologically induced vasoconstriction, hypoxia, hyperoxia, and acute normovolemic anemia. Hydrogen gas clearance was used as a reference method. After vasopressin infusion, LDV signal and indexes of hemoglobin (IHb) and oxygen (ISO2) content in the gastric mucosa estimated by RS significantly decreased in parallel with the reduction of gastric mucosal blood flow (GMBF). Neither hypoxia (5% O2 administration) nor hyperoxia (100% O2) affected GMBF or LDV signal. However, both IHb and ISO2 significantly decreased or increased after hypoxia or hyperoxia, respectively. Acute normovolemic anemia induced a significant increase in GMBF, while LDV signal and ISO2 remained unchanged. IHb significantly decreased in linear relationship with the decrements in the hematocrit. It is concluded that 1) in pharmacologically induced GMBF changes, LDV and RS correlate with GMBF; 2) when changes in hemoglobin saturation are induced, LDV but not RS reflects GMBF; and 3) in acute normovolemic anemia, neither LDV nor RS reflects changes in GMBF. PMID- 1443155 TI - Sodium- and chloride-conductive pathways in cultured mouse tracheal epithelium. AB - The utility of a transgenic murine model of cystic fibrosis (CF) lung disease will likely depend on whether the mouse's proximal airway epithelium is characterized by Na(+)- and Cl(-)-conductive pathways comparable to those found in human airways. Therefore, the electrophysiological properties of primary cultures of mouse tracheal epithelium (MTE) were investigated using double barreled, Cl(-)-selective microelectrodes. Epithelial cells isolated from freshly excised mouse tracheae formed confluent polarized monolayers on permeable collagen supports and developed significant transepithelial potential differences (approximately -10 mV) within 5-6 days postseeding. Under basal conditions, the MTE monolayers had an equivalent short-circuit current (Ieq) of -21.1 +/- 2.1 microA/cm2 and a transepithelial resistance of 424 +/- 49 omega.cm2. Intracellular measurements indicated that the apical (Va) and basolateral (Vb) membrane potential differences were -16.9 +/- 1.5 and -25.4 +/- 1.5 mV, respectively; apical membrane fractional resistance was 0.36 +/- 0.03; and intracellular Cl- activity was 56.1 +/- 2.3 mM. The presence of an apical Na+ conductance was demonstrated by luminal amiloride application (10(-4)M), which decreased Ieq, hyperpolarized Va, and increased the fractional resistance of the apical membrane. The presence of an apical Cl- conductance was demonstrated by substitution of Cl- with gluconate in the luminal bath, which decreased intracellular Cl- activity and increased the fractional resistance of the apical membrane. Luminal application of ATP (10(-4) M was also found to increase the rate of Cl- secretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443156 TI - Differential systemic and intrapulmonary TNF-alpha production in Candida sepsis during immunosuppression. AB - Candida albicans (CA) increasingly causes septic shock, acute lung injury, and multiple organ damage during immunosuppression-related neutropenia. However, the effects of neutrophil (PMN) depletion on induction of tumor necrosis factor-alpha (TNF) by CA and its potential mediation of Candida septic shock are unknown. We hypothesized that reduced CA uptake by circulating PMNs during cyclophosphamide (CY)-related neutropenia sensitizes to TNF-mediated shock from enhanced cytokine production after phagocytosis by tissue macrophages. Absolute or relative neutropenia (PMNs < or = 500/microliters or 2,500/microliters) was modeled in rats by intraperitoneal CY 4-8 days before 10(9) yeast-phase CA (acute studies < or = 24 h, n = 81 animals) or 10(6) CA (subacute studies < or = 72 h, n = 25). Compared with neutrophil-sufficient rats, absolute neutropenia accelerated hemodynamic collapse and respiratory distress after 10(9) CA, and pulmonary microvascular permeability was amplified. These changes evolved without increased candidemia or elevations in bioactive or antigenic serum TNF, which remained low even at death (42.3 +/- 14.8 U/ml vs. 12.6 +/- 2.9 U/ml for CY + saline, means +/ SE, P = NS). In contrast, significant TNF in lung tissue and bronchoalveolar lavage fluid (BALF) was evident within 6 h in CY + 10(9) CA rats. Electron microscopy confirmed hyphal proliferation into alveoli from yeast within mononuclear cells in lung capillaries. Subacute disseminated candidiasis after 10(6) CA was not associated with elevated serum, lung, or BALF TNF. We conclude that differential systemic and intrapulmonary TNF production occur in CA septic shock during preexisting neutropenia, with compartmentalized TNF production in the lower respiratory tract accompanying yeast-mycelial transformation. Thus TNF is not an obligate mediator of acute candidemic shock or subacute disseminated candidiasis during CY-induced immunosuppression but may initiate pulmonary injury accompanying high-grade candidemia. PMID- 1443157 TI - Expression and regulation of human pulmonary fibroblast-derived monocyte chemotactic peptide-1. AB - Monocyte recruitment is essential for maintenance of normal pulmonary macrophage populations. In addition, acute and chronic inflammatory pulmonary diseases are associated with sequestration of mononuclear phagocytes in the lung. Although alveolar macrophages (AM phi) can secrete a number of potent inflammatory and chemoattractment mediators, these immune cells do not produce monocyte chemotactic peptide (MCP-1) in response to lipopolysaccharide (LPS), tumor necrosis factor (TNF), or interleukin-1 beta (IL-1 beta). The pulmonary fibroblast (PF) may play a pivotal role in monocyte recruitment. In these studies, we demonstrate a time- and dose-dependent production of PF-derived steady-state MCP-1 mRNA, MCP-1 antigen, and monocyte chemotactic bioactivity attributable to MCP-1. In cellular models examining cytokine networks between AM phi and PF, LSP-stimulated AM phi (conditioned media) induced PF-derived steady state MCP-1 mRNA expression that was markedly attenuated by the presence of neutralizing TNF and IL-1 beta antibodies. Furthermore, we showed the dose- and time-dependent suppression of IL-1 beta-stimulated PF-derived MCP-1 by dexamethasone and prostaglandin E2. These findings demonstrated that PF are an important cellular source of MCP-1 and this production of MCP-1 may be influenced by immunomodulators. PMID- 1443158 TI - Murine pulmonary surfactant SP-A gene: cloning, sequence, and transcriptional activity. AB - SP-A is an abundant pulmonary surfactant-associated protein whose expression is controlled in a cell- and developmental-specific manner. To analyze regulation of SP-A gene expression, the murine SP-A gene was cloned and sequenced. The murine DBA/2J gene was approximately 4.6 kb in length comprised of six exons and five introns. Three mRNAs of 3.0, 1.7, and 0.9 kb were detected by Northern blot analysis of murine lung mRNA. Expression of the SP-A mRNAs was first detected at day 15 of gestation and increased dramatically before birth. A single SP-A gene was detected in the DBA/2J mouse genome. SP-A mRNA was detected in lung but not in the gastrointestinal tract, kidney, brain, liver, or heart and was detected by in situ hybridization in bronchial and alveolar cells of the murine lung. Primer extension analysis with a primer to exon three revealed two extension products differing by 9 bp in length, suggesting two closely juxtaposed transcription initiation sites. Chimeric gene(s) containing 1.8 kb of 5' SP-A sequences and the bacterial chloramphenicol acetyltransferase gene were expressed in pulmonary adenocarcinoma cells and in HeLa cells. Expression of the murine SP-A gene is partially controlled by non-cell-selective transcriptionally active sequences. PMID- 1443159 TI - Role and mechanism of thromboxane-induced proliferation of cultured airway smooth muscle cells. AB - Thromboxane (Tx)A2 has been reported to play an important role in modulating airway contractility under various conditions associated with airways inflammation. To identify its potential role in contributing to airway smooth muscle (ASM) hyperplasia, a characteristic feature of asthmatic airways, the mitogenic effect and mechanism of action of TxA2 were investigated in cultured rabbit ASM cells. The stable TxA2 mimetics, carbocyclic TxA2 (CTA2) and U-46619, elicited dose-dependent (10(-12) to 10(-6) M) increases in ASM cell number and induced acute augmentation of intracellular inositol 1,4,5-trisphosphate accumulation. The latter action was blocked by neomycin, a phospholipase C inhibitor; however, neomycin had no effect on the promitogenic action of the TxA2 mimetics. In contrast, TxA2-induced ASM cell proliferation was inhibited by inhibitors of phospholipase A2 and 5-lipoxygenase, as well as blockade of the leukotriene (LT)D4 receptor. Moreover, in complementary studies, we found that exogenous administration of LTD4 (10(-14) to 10(-6) M) potently induced ASM cell proliferation and that the TxA2 mimetics evoked the enhanced release of endogenous leukotrienes from the cultured ASM cells. Taken together, these observations provide new evidence that 1) TxA2 stimulates ASM cell proliferation; 2) the promitogenic effect of TxA2 is associated with activation of phospholipase A2; and 3) the latter mediates ASM cell proliferation via the release and autocrine mitogenic action of leukotrienes. The findings support a potential role for TxA2 in contributing to the characteristic increase in ASM cell mass obtained in asthma and other chronic airway diseases. PMID- 1443160 TI - Characteristics of magnetically separated rat tracheal epithelial cell populations. AB - A simple magnetic separation technique has been developed using lectins specific for two of the cell types found in the tracheal mucosa. The resulting populations of basal and secretory cells were examined for proliferative capacity in culture and in vivo. The basal cell fraction contains the cells that proliferate in culture and respond to 12-O-tetradecanoylphorbol-13-acetate. In addition, the basal cell fraction exhibited the highest proliferative capacity in vivo during the first few days after transplantation. Repopulation of inverted intestinal segments showed that only with suspensions containing a significant proportion of basal cells could a mucociliary lining be established. Segments receiving the same number of unsorted or predominantly mucous secreting cells did not repopulate in vivo. These data support the hypothesis that the basal cell is most likely the stem cell of the tracheal epithelium. PMID- 1443161 TI - Methylene blue inhibits neurogenic cholinergic vasodilator responses in the pulmonary vascular bed of the cat. AB - The effects of methylene blue, an inhibitor of soluble guanylate cyclase, on pulmonary vasodilator responses to efferent vagal stimulation were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. In animals pretreated with reserpine or phenoxybenzamine, under elevated tone conditions, efferent vagal stimulation at frequencies of 2-16 Hz caused stimulus-frequency-dependent decreases in lobar arterial pressure and pulmonary lobar vascular resistance. The vasodilator response to vagal stimulation was reproducible, blocked by atropine, and reduced by methylene blue. Intralobar infusion of methylene blue increased lobar arterial pressure without significantly altering systemic arterial or left atrial pressure. Methylene blue had no significant effect on vasodilator responses to isoproterenol, albuterol, atriopeptin III, lemakalim, adenosine, ATP, and pituitary adenylate cyclase activating polypeptide-27 but significantly decreased vasodilator responses to acetylcholine, nitric oxide (NO), sodium nitroprusside, and the S-nitrosothiol, S nitroso-N-acetyl-penicillamine. The effects of methylene blue on responses to vagal stimulation were reversible and were similar with the addition of a NO synthase inhibitor. The present data suggest that vasodilator responses to cholinergic nerve stimulation involve an increase in the production of guanosine 3',5'-cyclic monophosphate in the pulmonary vascular bed. These results provide additional evidence to support the hypothesis that neurogenically released acetylcholine induces endothelium-dependent, muscarinic, guanylate cyclase mediated vasodilation. PMID- 1443162 TI - Quantitation of alveolar distribution of liposome-entrapped antioxidant enzymes. AB - Liposome-encapsulated Cu,Zn superoxide dismutase (Cu,Zn SOD) and catalase (CAT) were instilled intratracheally in rabbits, and the temporal and spatial distribution of Cu,Zn SOD and CAT within the lung was assessed at the organ and cellular levels. Specific activities of Cu,Zn SOD and CAT were increased in both lung homogenates and isolated alveolar type II pneumocytes. Peak Cu,Zn SOD activities in lung homogenates and alveolar type II cells were observed 4 h after liposome instillation and returned to control levels by 24 h, whereas CAT activities remained significantly above controls. There were no significant differences in liposome distribution or antioxidant enzyme uptake among lung lobes. The distribution of fluorescently labeled Cu,Zn SOD and CAT was assessed with the use of epifluorescence microscopy and digital image processing to determine patterns of cellular incorporation of liposome-entrapped Cu,Zn SOD and CAT within the lung. Although the mean fluorescence intensity of alveoli from rabbits instilled with liposomes containing labeled Cu,Zn SOD and CAT was greater than autofluorescence observed with either no liposome or empty liposome instillation, fluorescence intensity varied between adjacent alveoli. Both fluorescently labeled Cu,Zn SOD and CAT were located cytosolically, and uptake was not limited to alveolar type II pneumocytes. These results demonstrate that a single intratracheal instillation of liposomes can effect increases in Cu,Zn SOD and CAT activities in distal lung cells, including alveolar type I and type II cells and macrophages. PMID- 1443163 TI - Stretching increases calcium influx and efflux in cultured pulmonary arterial smooth muscle cells. AB - To determine the effect of a single static stretch on calcium fluxes in cultured pulmonary arterial smooth muscle cells (PASMC), calcium influx and efflux were evaluated in PASMC on a collagen-coated silicone membrane using 45Ca2+ as a tracer. A single 20% linear stretch of the silicone membrane of 1 min in duration increased calcium uptake by 71%. This effect was partially inhibited by verapamil or gadolinium, but was not altered by staurosporine, pertussis toxin, or removal of extracellular sodium. Stretch-stimulated calcium uptake attenuated over time, such that uptake during the last minute of a 5-min sustained stretch was 46% of that during the first minute of stretch. A single 20% stretch sustained for 6 min caused a 47% increase in calcium efflux, the magnitude of which was linearly related to the degree of cell stretch. Gadolinium and removal of extracellular calcium each partially inhibited stretch-induced calcium efflux. We conclude that a single static stretch of PASMC causes increases in both calcium influx and efflux. Stretch-stimulated calcium influx does not require sodium influx and is mediated in part by a pathway sensitive to both gadolinium and verapamil. Stretch stimulated calcium efflux is due to both calcium influx via a gadolinium sensitive pathway and mobilization of intracellular stores. Because calcium is a key cellular second messenger, these effects of stretch on cellular calcium handling may play a role in the regulation of vascular smooth muscle cell phenotype and function. PMID- 1443164 TI - Surfactant protein C is recycled from the alveoli to the lamellar bodies. AB - To clarify the life cycle of surfactant protein C (SP-C), we obtained alveolar surfactant from 3-day-old rabbits killed 15 h after the tracheal administration of 32P and L-[35S]methionine. Small amounts of this surfactant were administered into the tracheas of 3-day-old rabbits, which were killed after 1 min and 2 and 4 h. We then analyzed the radioactivity associated with SP-C and with saturated phosphatidylcholine (DPPC) in lung lavage fluid and in a lamellar body-rich fraction isolated from the lung homogenate. We found that SP-C and DPPC are both taken up from the alveolar spaces and incorporated into lamellar bodies, but the time courses of reuptake are different. Our results indicate that in the alveoli SP-C is turned over faster than DPPC. PMID- 1443165 TI - Pathways for glucose transport in type II pneumocytes freshly isolated from adult guinea pig lung. AB - Previous in vivo studies of sugar transport across the mature pulmonary epithelium have provided evidence for the existence of a specific phlorizin inhibitable, sodium-dependent transport process for D-glucose, although no direct evidence for the cellular location of this transport system in fresh cells has been shown to date. With the use of elastase digestion and lectin agglutination, a pure preparation of type II alveolar epithelial cells was isolated from adult guinea pig lung. This preparation always contained >90% type II cells and typically showed approximately 85% cell viability 2-3 h after the isolation procedure had begun. At 37 degrees C, cells showed specific [3H]phlorizin binding that was attenuated by D-glucose and completely abolished by sodium replacement. Substantial accumulation of the hexose [14C]methyl alpha-D-glucopyranoside (14C labeled AMG), a substrate specific for the sodium-dependent glucose cotransporter was found in the presence of extracellular sodium; this accumulation above equilibrium was abolished on removal of sodium, addition of phlorizin, or in the presence of a saturating concentration (69 mM) of D-glucose. The apparent inhibition constant (Ki) for glucose inhibition of AMG uptake was 0.4 mM and for phlorizin, 0.5 microM. The Hill plot of sodium activation of AMG uptake gave a coefficient of 2.8, suggesting cooperativeness between sodium and AMG transport. 3-O-[14C]methyl-D-glucose (3-OMG) transport was also blocked by phlorizin. Phloretin, in the presence of phlorizin, slowed the initial rate of entry but did not affect the equilibrium that was attained in the presence of phlorizin alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443166 TI - Protective and specificity-conferring mechanisms of mineralocorticoid action. AB - Several experiments using both the in vivo rat bioassay and the isolated toad bladder preparation have been reported that lend support to the hypothesis that the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), in mineralocorticoid (MC) target tissues, acts as a "protective" mechanism that prevents endogenous glucocorticoids (GCs) from causing MC receptor-mediated effects on Na+ and K+. Additional experiments have also indicated that a second distinct protective mechanism exists that prevents endogenous MCs from eliciting excessive MC receptor-mediated Na+ retention. This second protective mechanism may involve steroid-metabolizing enzymes other than 11 beta-OHSD. Since the specific GC agonist, RU28362, can elicit Na+ retention and K+ secretion, it is possible that a third protective mechanism exists whereby renal 11 beta-OHSD prevents endogenous GCs from eliciting GC receptor-mediated effects on Na+ and K+. PMID- 1443167 TI - Induction and intracellular localization of HSP-72 after renal ischemia. AB - To determine whether heat shock proteins (HSPs) might be active in cellular recovery following transient ischemia, we examined rat kidneys for 70-kDa HSP (HSP-70) mRNA expression, protein elaboration, and intracellular localization after 45 min of renal ischemia and reflow of 15 min, 2, 6, and 24 h. Inducible HSP-70 mRNA is present at 15 min of reperfusion, peaks between 2 and 6 h, and falls by 24 h. Inducible 72-kDa HSP (HSP-72) protein accumulates progressively through 24 h and is found in both soluble and microsomal fractions following ischemia. Within proximal tubules, immunofluorescent localization of HSP-72 is restricted to the apical domain at 15 min, is dispersed through the cytoplasm in a vesicular pattern at 2 and 6 h, and has migrated away from the apical domain at 24 h. A portion of the vesicular HSP-72 is associated with lysosomes; no intranuclear HSP-72 is detected. The course of mRNA induction, protein elaboration, and HSP-72 localization coincides with previously described changes in proximal tubule morphology and polarity following sublethal ischemic injury. HSP-72 may be instrumental in cellular remodeling and restitution of epithelial polarity during recovery from ischemic renal injury. PMID- 1443168 TI - Macrophages mediate adverse effects of cholesterol feeding in experimental nephrosis. AB - We tested whether the deleterious effects of hypercholesterolemia, in a progressive glomerular disease model, may be mediated by infiltrating renal macrophages. A single sublethal dose of whole body X-irradiation (XI) delivered to rats with acute puromycin aminonucleoside (PA) nephrosis fed a high cholesterol (HC) diet resulted in significantly greater inulin and p aminohippurate (PAH) clearances at 11 days after PA without any alterations in circulating lipid levels, in contrast to nonirradiated HC-fed nephrotic controls. This functional protection was associated with significant declines in both glomerular and cortical interstitial macrophage number. Over the course of this 16-wk model, HC-fed PA rats had significantly less albuminuria as well as significantly fewer glomerulosclerosis (GS) lesions and less mesangial matrix expansion at the end of the study despite an equivalent degree of sustained hypercholesterolemia. This data suggests that reducing the infiltrating glomerular and cortical interstitial macrophage burden with XI during acute PA nephrosis, unaccompanied by any hypolipidemic effect, produces not only early salutary effects on renal function but also a significant amelioration of the progressive glomerulopathic features of this model. This is consistent with the hypothesis that the infiltrating renal macrophage, in large part, directly mediates the adverse effects of hypercholesterolemia in this model. PMID- 1443169 TI - Chloride transport in a mathematical model of the rat proximal tubule. AB - The proximal tubule model of this laboratory [Am. J. Physiol. 250 (Renal Fluid Electrolyte Physiol. 19): F860-F873, 1986] has been updated to examine proposed pathways for Cl- transport. Two additional buffer pairs have been added, i.e., HCO2-/H2CO2 and NH3/NH4+. At the luminal cell membrane Cl-/HCO2- and Cl-/HCO3- exchange are considered as pathways for Cl- entry, whereas at the peritubular membrane, Cl- exit occurs by either Na(+)-2HCO3-/Cl- exchange or K(+)-Cl- cotransport. Calculations with this model indicate that absolute proximal reabsorption of both Na+ and Cl- are critically dependent on the rate of luminal Na+/H+ exchange. In contrast, increases in the coefficient for Cl-/HCO2- exchange have little impact on overall Cl- flux, but, by enhancing base secretion, limit the depression of end-proximal HCO3-. Model calculations confirm those of Preisig and Alpern (J. Clin. Invest. 83: 1859-1867, 1989) showing that their measured value of luminal membrane H2CO2 permeability is inadequate to sustain the transcellular Cl- flux as Cl-/HCO2- exchange. Conversely, with sufficiently high H2CO2 permeability, luminal Cl- uptake is enhanced along the tubule, as HCO2- secretion and luminal acidification increase luminal H2CO2 to values severalfold greater than in glomerular filtrate. At the basolateral membrane, the thermodynamic driving force across the Na(+)-2HCO3-/Cl- exchanger is small. Although its contribution to steady-state Cl- exit may be less than the K(+)-Cl- cotransporter, the Na(+)-2HCO3-/Cl- exchanger can be a mechanism by which cytosolic acidification enhances peritubular Cl- transport, when luminal acidification enhances luminal Cl- uptake. A simulation is presented in which impermeant replacement of luminal Na+ leads to enhanced convective Cl- flux across the tight junction and alkalinization of the lateral interspace. In this setting, cytosolic Cl- depletion via the Na(+)-2HCO3-/Cl- exchanger may mimic luminal membrane Na(+)-Cl- cotransport. PMID- 1443170 TI - Rat kidney aldose reductase and aldehyde reductase and polyol production in rat kidney. AB - Mounting evidence indicates that aldose reductase catalyzed reduction of excess glucose to sorbitol initiates the onset of certain diabetic complications. However, the kidney contains a large amount of aldehyde reductase, another NADPH dependent reductase. The study was designed to assess the importance of these reductases to sugar alcohol (polyol) production in the kidney. To study the ability to reduce aldoses to polyols, both aldose and aldehyde reductases were purified from rat kidneys. Incubation studies with purified enzymes clearly demonstrated the polyol formation by both enzymes. Galactose feeding induced polyol accumulation in both medulla and cortex of the rat kidney. Al 1576, a potent inhibitor of both enzymes, reduced this polyol accumulation in both cortex and medulla, while the selective inhibitors Ponalrestat or FK 366 resulted in greater inhibition in medulla than cortex. These results suggest that kidney polyols may be generated by both aldose and aldehyde reductases and that aldehyde reductase contributes to polyol production in the kidney cortex, the predominant site of diabetes-linked kidney lesions. PMID- 1443171 TI - Epidermal growth factor accelerates renal tissue repair in a model of gentamicin nephrotoxicity in rats. AB - Epidermal growth factor (EGF) is a potent mitogen for renal tubular cells that possess specific high-affinity binding sites for this polypeptide. However, actual function of EGF within the kidney remains to be elucidated. We evaluated the effect of exogenous EGF administration on the rate of tubular regeneration in an experimental model of gentamicin (GT) nephrotoxicity. Female Sprague-Dawley rats were anesthetized, and a miniosmotic pump filled with mouse EGF or saline was implanted subcutaneously. Twenty-four hours later, GT (40 mg.kg-1 x 12 h-1 ip) was given for 4 and 8 days. Groups of treated animals and controls were killed either the day after cessation of treatment (days 5 and 9) or 4 and 8 days after the end of 8-day GT administration (days 12 and 16). Cortical GT levels of groups killed at days 5, 9, 12, and 16 were similar in animals infused with saline or EGF. Serum creatinine levels were significantly higher in GT-treated animals infused with EGF or saline and killed at days 9 and 12 compared with saline-treated animals infused with EGF or saline alone (P < 0.01). Blood urea nitrogen (BUN) also increased as a result of GT administration. However, in animals receiving GT and EGF and killed at day 16, mean BUN level was significantly lower (P < 0.01) compared with rats dosed with GT alone. In treated rats, the extent of tubular regeneration, evaluated by the rate of [3H]thymidine incorporation into renal cortical DNA or by the frequency of S-phase cells (histoautoradiography), was increased in a dose- and time-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443172 TI - Erythropoietin metabolism and pharmacokinetics in experimental nephrosis. AB - We studied erythropoietin (EPO) metabolism, regulation, and pharmacokinetics in rats with nephrotic syndrome. Sprague-Dawley rats were randomized into nephrotic (puromycin-induced) and pair-fed control groups. Animals were studied at baseline and after induction of anemia or exposure to hypobaric conditions (32 cmHg). The nephrotic group showed a reduced hematocrit (P < 0.05), a significant urinary EPO excretion, and an inappropriately low plasma EPO. Induction of anemia and exposure to hypoxia resulted in a less pronounced elevation of plasma EPO in the nephrotic group than in the control group (P < 0.05). The blunted plasma EPO response to hypoxia in nephrotic animals was associated with a marked rise in urinary EPO excretion. Pharmacokinetic studies following intravenous injection of recombinant EPO, 100 U/kg, revealed a shorter plasma half-life (t1/2) (P < 0.05), larger apparent volume of distribution (P < 0.05), and greater clearance (P < 0.02) in the nephrotic group than in the controls. Estimated endogenous EPO production rate in nephrotic rats with severe anemia was significantly lower (P < 0.05) than that of equally anemic controls. Thus puromycin-induced nephrotic syndrome is associated with marked urinary loss of EPO, relatively depressed plasma EPO response to anemia and hypoxia, as well as reduced plasma t1/2, increased volume of distribution, and clearance of exogenous EPO. PMID- 1443173 TI - Renal hemodynamic effects of exogenously administered adenosine and polyadenylic acid. AB - Steady-state intrarenal arterial infusion of adenosine (Ado) suggests that there may be both afferent and efferent arteriolar actions of Ado. This study attempts to further differentiate vascular sites of action of Ado during an intrarenal infusion of Ado. We measured the filtration fraction (FF) during intrarenal infusion of Ado (33.3 nmol.kg-1 x min-1) in anesthetized dogs to determine its transient actions on renal hemodynamics. FF remained unchanged from preinfusion levels (0.42 +/- 0.01 vs. 0.46 +/- 0.01, respectively) at a time when renal blood flow (RBF) was significantly decreased (52 +/- 6% of control). During steady state, RBF was 96 +/- 5% of control, while FF was significantly decreased from control (0.27 +/- 0.02). To determine whether vasoconstriction and dilation to Ado are mediated by receptors accessible from intra- or extravascular compartments, two Ado analogues [oligoadenylic acid (oligo[A]), mol wt 5,000, and polyadenylic acid (poly[A]), mol wt > 100,000] were injected into the renal artery, and RBF response was compared with that of Ado. Poly[A] produced a transient vasodilation (42 +/- 6% increase in RBF), whereas oligo[A] produced a transient vasoconstriction (25 +/- 5% decrease in RBF). Responses to steady-state infusion of poly[A] (10 nmol.kg-1 x min-1) were determined in 11 anesthetized sodium-depleted dogs. Poly[A] produced a sustained significant increase in RBF from 2.83 +/- 0.31 to 3.92 +/- 0.40 ml.g-1 x min-1. This decrease in renal vascular resistance was blocked by an intrarenal infusion of the Ado antagonist theophylline (0.5 mumol.kg-1 x min-1, 2.68 +/- 0.38 vs. 2.85 +/- 0.38 ml.g-1 x min-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443174 TI - Folate transport and binding by cultured human proximal tubule cells. AB - Because mechanisms for the renal regulation of folate excretion are poorly understood, a cell culture system representative of the human proximal tubule (HPT) was used for studies of renal folate transport. After confluent cultures of HPT cells were incubated with 3H-labeled folic acid (PteGlu), binding to the apical membrane was determined by an acid removal procedure, and transport was subsequently measured in solubilized cells. Although PteGlu binding was almost all specific (suppressed by excess unlabeled PteGlu), HPT cells transported PteGlu by specific and nonspecific processes. Specific PteGlu binding and transport were both saturable processes, reaching maxima of 0.5 and 0.1 pmol/mg protein, respectively, with half-maximal constants of 12 and 50 nM, respectively. The PteGlu analogues methotrexate and 5-methyltetrahydrofolic acid (5-CH3 H4PteGlu) inhibited both the binding and transport of PteGlu, with 5-CH3-H4PteGlu being more potent (lower half-maximal inhibitory concentration). In contrast, 5 formyltetrahydrofolic acid significantly reduced PteGlu transport at concentrations (100-250 nM) that had no effect on binding. These data suggest that the HPT cells will serve as a good model for studies of renal folate reabsorption. Initial characterization of the transport of folate by HPT cells suggests two distinct processes, binding to a high-affinity membrane folate binding protein followed by a structurally specific transfer into the cell. PMID- 1443175 TI - Interaction of Cl- and other halogens with Cl- transport systems in rabbit cortical collecting duct. AB - We have reported that in the rabbit cortical collecting duct (CCD) we can identify electrophysiologically three distinct cell types; the collecting duct (CD) cell and the alpha- and beta-intercalated (IC) cell. To further characterize the Cl- transport properties of each cell type, we examined the interaction between Cl- and other halogens or SCN- in the isolated and perfused CCD by intracellular microelectrode impalement. The rapid depolarization of the basolateral membrane potential (VB) caused by replacement of bath Cl- with each anion revealed that the sequences of apparent halogen selectivity for the basolateral Cl- conductance were similar in all three cell types. The ranking of Cl- > Br- > F- > I- corresponds to the sequence 5 of Eisenman's series, indicating "strong" interaction of the anions with the selectivity site. The basolateral Cl- conductance of these three cell types may share common characteristics, although I- permeability is less in IC cells than in CD cells. Hyperpolarization of the basolateral membrane of the beta-IC cell upon reduction of luminal Cl- reflects alterations in either Cl- entry across the apical membrane, or Cl- exit across the basolateral membrane, or both. Luminal Cl- replacement with each anion showed that the sequence of the hyperpolarization of the basolateral membrane was I- >> cyclamate = SCN- > F- > Br-, suggesting that I inhibits either apical Cl- entry or basolateral Cl- exit. On the other hand, in the CD cell reduction of the perfusate Cl- by replacement with each anion caused the basolateral membrane to hyperpolarize with a different ranking: cyclamate = F > I- = SCN- > Br-.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443176 TI - Localization of urea and ornithine production along mouse and rabbit nephrons: functional significance. AB - Hydrolysis of arginine into urea and ornithine (Orn) was observed to take place in several segments of the rat nephron including cortical and medullary pars recta of the proximal tubule (PST) and collecting duct (CD). This work was now extended to the adult mouse and rabbit. Representative nephron segments, obtained by microdissection of collagenase-treated kidneys, were incubated with L-[guanido 14C]arginine (216 microM). Addition of urease produced 14CO2 + 2 NH3 from the newly formed urea released in the incubate. 14CO2 was trapped in KOH and counted. In both species, as well as in the rat, the PST was the site of the highest urea + Orn production, with an intensity increasing from cortex to medulla. For other nephron segments, the pattern was not similar in all species. Significant production of urea + Orn was observed in the proximal convoluted tubule and the medullary thick ascending limb in the rabbit, but not in the CD of either the rabbit or the mouse. The functional significance of this urea + Orn production remains unclear. The total amount of urea generated intrarenally by this reaction does not seem sufficient to play a significant role in the urinary concentrating mechanism. It may be assumed that Orn could be further metabolized to polyamines and play a role in maintaining cell integrity and function in the PST, especially in its medullary part, exposed to hypertonicity and poor oxygen supply. PMID- 1443177 TI - Effects of ATP on pre- and postglomerular juxtamedullary microvasculature. AB - Based on evidence that extracellular ATP can influence vascular smooth muscle function in other organ systems, experiments were conducted to characterize the responsiveness of rat juxtamedullary microvascular segments to ATP. Experiments were performed using the in vitro blood-perfused juxtamedullary nephron preparation combined with video microscopy. Pentobarbital-anesthetized rats were pretreated with enalaprilat (2 mg iv) for 30 min before the right kidney was isolated and prepared for study. Renal perfusion pressure was set at 110 mmHg and held constant. Under control conditions, afferent and efferent arteriolar diameters averaged 19.9 +/- 1.4 (n = 19) and 21.6 +/- 1.2 microns (n = 10), respectively. Superfusion with 1, 10, and 100 microM ATP solutions induced sustained dose-dependent afferent vasoconstriction of 8.3 +/- 1.4, 12.8 +/- 1.7, and 12.1 +/- 2.1%, respectively (P < 0.01). Afferent vasoconstrictor responses to ATP were also observed during adenosine receptor blockade. In contrast, efferent arterioles were unresponsive to ATP stimulation even at concentrations as high as 100 microM (P > 0.05). Arcuate and interlobular arterial diameters averaged 82.0 +/- 15.7 (n = 5) and 43.4 +/- 4.5 microns (n = 6), respectively, during control conditions and responded to ATP treatment with a transient vasoconstriction followed by a gradual return to control diameter. Interlobular arteries exhibited a sustained constriction only at the 100 microM concentration (P < 0.05). These data demonstrate that afferent arterioles are more responsive to ATP treatment than other renal microvascular segments and suggest the presence of ATP-sensitive P2x purinoceptors on pre- but not postglomerular juxtamedullary microvascular elements. PMID- 1443178 TI - Comparative sensitivities of isolated rat renal arterioles to endothelin. AB - The specific intrarenal sites and mechanism of endothelin (ET) vascular action are controversial. In this study afferent (AA) and efferent arterioles (EA) were isolated from the kidneys of normal Sprague-Dawley rats. Their respective concentration-dependent changes in lumen diameter in response to ET-1 were compared with those of angiotensin II (ANG II) and norepinephrine (NE). In a second series of experiments, the duration of vasoconstriction to comparable transient submaximal ET-1, ANG II, and NE concentrations in AA and EA was examined. The role of angiotensin II in mediating endothelin vasoconstriction also was examined with the converting-enzyme inhibitor captopril (CAP) and the competitive inhibitor [Sar1,Ala8]ANG II (SAR). The half-maximal constriction concentration (EC50) of ET-1 was less in EA than AA (P < 0.01). EC50 of ET-1 in AA was similar to that of ANG II, but was less than that of NE (P < 0.001). In EA the EC50 of ET-1 was also similar to that of ANG II, but much less than that of NE (P < 0.001). In both AA and EA the duration of ET-1 constriction was at least twice that of ANG II and more than fivefold that of NE. Neither CAP (10(-6) M) nor SAR (10(-7) M) changed the vasoconstrictor response to submaximal concentrations of ET-1 in AA or EA. It is concluded that ET-1 is a potent and prolonged constrictor agonist with a small, but significantly greater, concentration-dependent effect in EA than AA. The constrictor effect of ET-1 does not require ANG II activity. PMID- 1443179 TI - Arginine augments neither albuminuria nor albumin synthesis caused by high protein diets in nephrosis. AB - Dietary protein independently modulates albuminuria (U(Alb)V) and albumin synthesis (AlbSyn) in nephrotic rats. While some amino acids are without effect on renal hemodynamics, arginine (Arg) augments renal blood flow and glomerular filtration rate, increases AlbSyn in tissue culture and isolated perfused livers, and could be one specific amino acid causing both decreased glomerular permselectivity and increased AlbSyn. Nephrotic rats were fed 10% casein (LP); 30% casein (HP); 30% casein with the inhibitor of nitric oxide (NO) synthesis N omega-nitro-L-arginine methyl ester (HP + L-NAME); 10% casein supplemented with Arg and amino acids that are Arg precursors of or are derived from Arg (proline, glutamate, and aspartate) in an amount in the increment between 10 and 30% casein (ArgAA); ArgAA supplemented with NH4 acetate to provide a diet isonitrogenous to 30% casein (ArgAA + NH4); or 10% casein plus an incomplete mixture of amino acids (Inc) containing the increment in histidine, phenylalanine, tryptophan, tyrosine, lysine, glycine, alanine, serine, threonine, cysteine, and methionine provided when the diet was changed from 10 to 30% casein. U(Alb)V increased significantly in HP and by a significantly greater amount in HP + L-NAME, but did not change in LP, ArgAA, or ArgAA + NH4. U(Alb)V tended to increase in Inc, was significantly greater than in LP or in ArgAA + NH4, but less than in HP. AlbSyn ([3H]phenylalanine incorporation) was no different in Inc than in HP, and was significantly greater than in either ArgAA + NH4 or LP. Increased AlbSyn results from increased ingestion of one or more of amino acids in Inc, but not from Arg or its precursors or products or from total dietary nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443180 TI - Renal innervation plays no role in oxygen-dependent control of erythropoietin mRNA levels. AB - To assess the role of renal innervation in O2-dependent control of erythropoietin (EPO) formation, we have determined EPO mRNA levels in both kidneys of unilaterally denervated rats and sham-operated controls using RNase protection. To investigate whether possible effects of renal nerve input are related to the type of hypoxic stimulus and the degree of stimulation, animals were studied under basal conditions, after exposure to normobaric hypoxia (8% O2, 4 h) or CO (0.1%, 4 h), and after acute hemorrhage (decrease in hematocrit from 40.8 +/- 0.5 to 12.7 +/- 0.5% within 7 h; mean +/- SE, n = 6). Serum EPO levels rose on average 22-, 49-, and 48-fold under the three stimuli and were unaffected by unilateral denervation. Renal EPO mRNA levels in unilaterally denervated animals, when expressed in arbitrary units revealed by comparison with an external standard, were 7.0 +/- 1.5 vs. 6.3 +/- 2.0 (normoxia), 432 +/- 136 vs. 451 +/- 156 (normobaric hypoxia), 971 +/- 93 vs. 930 +/- 120 (CO), and 604 +/- 170 vs. 689 +/- 203 (hemorrhagic anemia) in the intact vs. the denervated kidney (mean +/ SE, n = 3). Furthermore, there was no difference between EPO mRNA levels of either kidney of unilaterally denervated animals and levels in sham-operated controls. We conclude that renal nerve input plays no significant role in the control of the EPO gene under both basal and stimulated conditions. PMID- 1443181 TI - Estimation of erythropoietin secretion rate in normal and uremic subjects. AB - We have developed a method for directly estimating the secretion rate of endogenous erythropoietin (EPO) in human subjects. Carrier-free recombinant human EPO was labeled with 125I by the chloramine T method. Human serum albumin was then added prior to removal of free iodide. Seven normal subjects and nine patients with chronic uremia and anemia were studied. Each subject received a bolus of 125I-EPO according to body size and then a constant infusion for 5 h. Secretion rate was calculated as the rate of infusion divided by serum EPO specific activity given by the protein-bound counts divided by the EPO concentration. Serum EPO concentration was significantly higher in the patients than the controls (mean 30.9 pg/ml vs. 11.1 pg/ml, P < 0.05), although all values were within the normal range. Mean EPO secretion rate was 255 in the patients (range 68-1,101) and 190 pg.kg-1 x h-1 in the normal group (range 52-382). This difference was not significant. As the subjects were in a steady state, EPO disappearance/degradation was the same in patients compared with controls despite a relatively hypoplastic marrow. PMID- 1443182 TI - Na(+)-Ca2+ exchanger of rat proximal tubule: gene expression and subcellular localization. AB - The activity of the Na(+)-Ca2+ exchanger, a membrane transporter that mediates Ca2+ efflux, has been described in amphibian and mammalian renal proximal tubules. However, demonstration of cell-specific expression of the Na(+)-Ca2+ exchanger in proximal renal tubules has been restricted to functional assays. In this work, Na(+)-Ca2+ exchanger gene expression in rat proximal tubules was characterized by three additional criteria: functional assay of transport activity in membrane vesicles derived from proximal tubules, expression of specific Na(+)-Ca2+ exchanger protein detected on Western blots, and determination of specific mRNA encoding Na(+)-Ca2+ exchanger protein on Northern blots. A new transport activity assay showed that proximal tubule membranes contained the highest Na(+)-Ca2+ exchanger transport activity reported in renal tissues. In dog renal proximal tubules and sarcolemma, a specific protein of approximately 70 kDa was detected, whereas in rat proximal tubules and sarcolemma, the specific protein approximated 65 kDa and was localized to the basolateral membrane. On Northern blots, a single 7-kb transcript isolated from rat proximal tubules, whole kidney, and heart hybridized under high-stringency conditions with rat heart cDNA. These data indicate that Na(+)-Ca2+ exchanger protein expressed in rat proximal tubule is similar, if not identical, to the cardiac protein. We suggest that the tubular Na(+)-Ca2+ exchanger characterized herein represents the Na(+)-Ca2+ exchanger described in functional assays of renal proximal tubules. PMID- 1443184 TI - A study of regional distribution of renal blood flow using quantitative autoradiography. AB - Quantitative autoradiography utilizing [14C]iodoantipyrine was used to measure regional renal blood flow in anesthetized rats. This technique allowed blood flow in any region of the kidney to be measured with a resolution of 100 microns. There was no significant difference between flow to polar and middle regions of the renal cortex [875 +/- 57 vs. 926 +/- 71 (SE) ml.100 g-1 x mm-1]. Areas of high optical density in renal cortex corresponded to peritubular capillaries. Mean cortical blood flow was three times greater than mean medullary blood flow. Outer medullary blood flow was uniform but significantly higher than inner medullary blood flow (272 +/- 16 vs. 45 +/- 7 ml.100 g-1 x mm-1; P < 0.001). PMID- 1443183 TI - Age-related changes in alpha 1- and alpha 2-chain type IV collagen mRNAs in adult mouse glomeruli: competitive PCR. AB - Studies of age-related changes in glomerular extracellular matrix (ECM) synthesis in normal mice have been hampered by the difficulty of isolating sufficient numbers of intact glomeruli and by the inability to quantify different mRNA species. The purpose of this study was to identify and quantitate the individual mRNAs coding for alpha 1- and alpha 2-chains of type IV collagen in isolated, single glomeruli of normal mice at different ages. These data on normal ECM synthesis were necessary for the understanding of glomerulosclerosis, a condition characterized by excess deposition of collagen. Pools of freshly microdissected adult mouse glomeruli were reverse transcribed in situ, and alpha 1-IV and alpha 2-IV collagen mRNAs were individually amplified by means of specific primers and the polymerase chain reaction (PCR), according to a previously published method. A competitive PCR assay, based on utilization of mutated cDNAs, allowed the reproducible, quantitative, and separate determination of the absolute amounts of both alpha 1-IV and alpha 2-IV mRNAs measured, as their respective cDNAs, in one tenth of one glomerulus. The levels of alpha 1-IV and alpha 2-IV collagen mRNA were 208 +/- 36.0 x 10(-4) and 161.2 +/- 18.6 x 10(-4) amol/glomerulus in 5-wk old mice. There were no significant age-related differences at 8, 12, and 24 wk. The mean levels over this period were 60.2 +/- 4.9 x 10(-4) for alpha 1-IV collagen mRNA and 63.9 +/- 5.8 x 10(-4) amol/glomerulus for alpha 2-IV collagen mRNA. Two of three 24-wk-old mice had mild glomerulosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443185 TI - Organ perfusion by dynamic scintigraphy convection-diffusion tracer kinetics in a phantom. AB - Dynamic scintigraphy is used widely to evaluate qualitatively the perfusion of an organ. Attempts to quantify blood flow to an organ by means of scintigraphic imaging modalities have often employed assumptions that lead to oversimplifying the physiology of the tracer kinetics. We used a mathematical formalism described by W. Perl and F. P. Chinard (Circ. Res. 22: 273-298, 1968), the convection diffusion tracer kinetics, model, for parameter evaluation of flow (F) and volume of distribution (V). This modeling methodology was evaluated using a circulatory phantom with absolute flow measured independently by flowmeter. In a series of 22 phantom experiments with F/V < 0.32 s-1, there was a strong correlation between F and flow probe measurement [r = 0.97; slope = 1.08 +/- 0.06 (SE)]. The theoretical analysis comparing this approach with classical tracer kinetics methods explains both the satisfactory results for F/V using mean transit time and the systematic overestimation of F/V using decay constant methods. PMID- 1443186 TI - Renal expression of the gene for atrial natriuretic factor. AB - To date, atrial natriuretic factor (ANF) mRNA has eluded detection in the mammalian kidney, although we and others have identified ANF protein in the kidney using immunohistochemical and immunoassay techniques. Furthermore, we have demonstrated the synthesis and secretion of the ANF prohormone in the distal cortical nephron of the intact rat kidney and from rat primary cultured renal distal cortical tubular epithelial cells. In the present study, we show that the ANF gene is expressed in the kidney. Amplification of RNA isolated from rat distal cortical tubular epithelial cultures using ANF specific primers produced a 213-bp fragment that specifically hybridized to a 32P-labeled ANF cDNA. We had previously demonstrated these cultures to be enriched for the renal ANF synthetic and secretory cell type. However, we were unable to detect an ANF gene transcript in total rat kidney RNA using the above-mentioned polymerase chain reaction (PCR) conditions. Reanalysis of normal rat kidney PCR products by a second round of PCR amplification using nested primers successfully identified ANF mRNA. Similar to cultured kidney epithelial cells, normal rat kidney expresses ANF mRNA, but at a very low abundance, thus necessitating two rounds of PCR amplification. Further characterization of rat cortical distal tubular epithelia poly(A)+ RNA by Northern analysis revealed two ANF gene transcripts. A 1.0-kb message that comigrated with rat atrial ANF mRNA, and a second larger 1.4-kb transcript. These studies further substantiate the synthesis of ANF in the mammalian kidney. Unlike the mammalian heart, the kidney contains two ANF gene transcripts. PMID- 1443187 TI - Regulatory effect of thromboxane A2 on proliferation of vascular smooth muscle cells from rats. AB - We investigated the regulatory effects of the vasoconstrictor thromboxane A2 on the proliferation of vascular smooth muscle cells (VSMC) from Wistar-Kyoto rats using 9,11-epithio-11,12-methano-thromboxane A2 (STA2), a stable analogue of thromboxane A2. STA2 dose dependently increased incorporation of [3H]thymidine into DNA in randomly cycling VSMC and significantly shortened the doubling time. Cell cycle analysis revealed that the increased cell cycle progression was primarily due to a rapid transition from the DNA synthetic (S) to the G2/mitotic (M) phase. Moreover, STA2 enhanced protein synthesis in VSMC during the G2/M phase, whereas the protein synthesis was unaffected in the G0/G1 period. In fact, STA2 prompted the cells in G2/M phase to synthesize actin, a major cytoskeleton protein. Conversely, inhibition of protein synthesis by puromycin retarded the transition from S to G2/M. In addition, depolymerization of the actin molecules by cytochalasin D offset the quick progression to the G2/M phase by STA2. These data indicate that thromboxane A2 stimulates the cell cycle progression in VSMC primarily through a rapid transition from S to G2/M. This enhanced progression is attributable partly to a rapid buildup of the cytoskeleton proteins during the G2/M period. PMID- 1443188 TI - Hypoxia-elicited contraction of aorta and coronary artery via removal of endothelium-derived nitric oxide. AB - To characterize endothelium-derived contracting factor 1 (EDCF1) released under hypoxia, vascular rings isolated from spontaneously hypertensive rat (SHR) aorta and canine coronary artery were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit buffer. In SHR aorta precontracted with norepinephrine (10(-7) M), severe hypoxia induced an initial increase in tension by 36.7 +/- 7.5% followed by a 56.9 +/- 5.7% relaxation; moderate hypoxia induced only a sustained increase in tension by 20.6 +/- 2.5%. Inhibition of nitric oxide (NO) production with N omega-nitro-L-arginine methyl ester (L-NAME) (10(-3) M) augmented norepinephrine-induced precontraction by 76.1 +/- 12.3% and totally eliminated the hypoxic contraction. In canine coronary arteries precontracted with KCl (30 mM) in the presence of indomethacin (10(-5) M), severe hypoxia caused a sustained increase in tension by 68.9 +/- 7.3%, which was also abolished with L-NAME. When L-NAME (10(-3) M) was given after the precontraction, both of these vessels developed sustained contractions under normoxia and moderate hypoxia. These results suggest that the vasocontraction currently considered to be induced by EDCF1 is not caused by a contracting factor but rather is a contracting phenomenon derived from continuous inhibition of basal NO synthesis during hypoxia. PMID- 1443189 TI - Spectrum analysis of sympathetic nerve activity and blood pressure in conscious rats. AB - This study tests whether the power spectrum of blood pressure (BP) provides information toward the sympathovagal balance of BP control by comparing the BP (femoral arterial catheter) spectrum with the spectrum of the efferent sympathetic nerve activity (SNA, bipolar electrode around splanchnic nerve). A remarkable resemblance between both spectra was found. A high-frequency component (HF) linked to respiration and a slower fluctuation type between 0.15 and 0.6 Hz (LF) were identified. There was a large and significant coherence only in the HF range of the BP and SNA power spectrum (P < 0.01). The phase lag of SNA and BP was roughly 200 ms. The recordings were repeated during pharmacological blockade in nine Wistar-Kyoto rats (WKY) and nine spontaneously hypertensive rats (SHR). alpha 1-Adrenoceptor blockade (prazosin) reduced the proportional LF power of BP in both rat strains (WKY P < 0.01, SHR P < 0.05) in favor of HF (WKY P < 0.01, SHR P < 0.01). Parasympathetic blockade (methylscopolamine) had no effect on proportions of power. Similarly, there were no significant differences in the proportional HF and LF power spectra of WKY and SHR. These data provide direct evidence for a relationship between the BP and SNA power spectra; however, only the acute changes in the sympathetic tone changed the LF-HF relationship. PMID- 1443190 TI - Role of ATP-sensitive potassium channels in ovine fetal pulmonary vascular tone. AB - To study the potential role of ATP-sensitive K+ (K+ATP) channels in fetal pulmonary vasoregulation, we studied the effect of a K+ATP channel agonist, lemakalim, and antagonist, glibenclamide, on the fetal pulmonary circulation in nine chronically instrumented late-gestation fetal lambs. Left pulmonary artery (LPA) blood flow was measured with an electromagnetic flow transducer. Brief (10 min) infusions of lemakalim at 3, 10, and 30 micrograms/min into the LPA produced dose-dependent increases in flow from 68 +/- 7 to 96 +/- 11, 160 +/- 15, and 204 +/- 34 ml/min, respectively. The duration of pulmonary vasodilation after the 10 min infusions of lemakalim at 3, 10, and 30 micrograms/min was 20 +/- 3, 47 +/- 10, and 55 +/- 15 min, respectively. Pulmonary blood pressure and flow did not change with intrapulmonary infusion of glibenclamide (10 mg), a K+ATP channel antagonist. Lemakalim-induced pulmonary vasodilation was not affected by nitro-L arginine (10 mg), a competitive inhibitor of endothelium-dependent relaxing factor, but was blocked by glibenclamide. Prolonged (2 h) intrapulmonary infusions of lemakalim (2-6 micrograms/min) increased pulmonary blood flow by 137%. The increase in pulmonary blood flow was sustained throughout the infusion. Systemic and pulmonary arterial pressures decreased during prolonged infusion. We conclude that K+ATP channels are present in the fetal pulmonary circulation, but do not participate in the regulation of basal pulmonary vascular tone. K+ATP channel activation produces sustained vasodilation that is not mediated by endothelium-derived relaxing factor. We speculate that birth-related stimuli activate K+ATP channels to enhance the pulmonary vasodilation that occurs at birth. PMID- 1443191 TI - Capillary length, tortuosity, and spacing in rat myocardium during cardiac cycle. AB - Microvascular geometry was evaluated in rat left ventricular midmyocardium (male Sprague-Dawley, n = 14), arrested in systole (S) or diastole (D), by bolus injections of CaCl2 or KCl, respectively. The histological method employed in this study allowed for the visualization of capillary pathways from arteriole to venule. Capillary length, as directly measured from terminal arteriole to collecting venule, was not significantly different between S and D groups, averaging 606 +/- 15 microns (pooled mean +/- SE). The capillary length tortuosity, defined as the ratio of the capillary length to the direct arteriovenous distance, was significantly increased in systolic-arrested hearts (S = 1.31 +/- 0.03; D = 1.18 +/- 0.02, P < 0.01). At the level of individual capillary segments, however, there was no increase in tortuosity in systolic arrested hearts (S = 1.17 +/- 0.03; D = 1.16 +/- 0.02). Intercapillary spacing was significantly more uniform in systolic-arrested hearts. These data suggest that in systole, capillary length and tortuosity are generally preserved, and capillary spacing is more uniform, serving to maintain geometric conditions for oxygen supply during the cardiac cycle. PMID- 1443192 TI - Corticoid regulation of atrial natriuretic factor secretion and gene expression. AB - This study investigated the acute effects of glucocorticoids and mineralocorticoids on atrial natriuretic factor (ANF) biosynthesis in vivo. Groups of male Sprague-Dawley rats were injected with 1 mg dexamethasone (Dex), 10 mg deoxycorticosterone acetate (DOCA) or vehicle alone. Different groups were studied after periods of 30 min to 8 h. Plasma and left atrial ANF concentrations and ANF mRNA levels were measured 2-8 h after corticoid injection. From 30 min to 2 h after injection, ANF mRNA was analyzed by quantitative and qualitative assessments. There was a two- to threefold increase in plasma levels of ANF in Dex-treated rats compared with controls at all time periods (P < 0.05). Although ANF plasma levels increased over time following DOCA treatment, they were not significantly different from control values. Dex treatment also increased normalized ANF mRNA levels 77% above control levels during the first 4 h after injection (P < 0.05). Thereafter there was a return of mRNA levels to that seen in controls. There was no qualitative difference in the ANF mRNA at any time as assessed by Northern hybridization. In contrast, DOCA increased ANF mRNA levels only after 8 h (P < 0.05). No significant changes in left atrial ANF content were noted during this study. In a separate study, Dex was administered to isolated left atria in vitro in a superfusion system. Superfusion with 2 x 10(-5) M Dex produced a 40% increase in ANF secretory rate within 20 min (P = 0.036). We conclude that Dex induces a direct rapid increase in ANF mRNA levels and ANF secretion in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443193 TI - Effect of coronary perfusion of heptanol or potassium on conduction and ventricular arrhythmias. AB - Abnormalities in cellular coupling, modulated in part by intracellular gap junctions, have an important role in the genesis of reentrant arrhythmias in the setting of chronic myocardial infarction. The effects of heptanol, which has a relatively selective action on gap junctional resistance at low concentrations, and potassium, which primarily affects active membrane properties, were assessed using a localized intracoronary infusion system in 11 normal dogs in vivo. Both agents caused a dose-related slowing of conduction. Programmed stimulation during potassium infusion resulted in ventricular fibrillation in two of six animals treated with a low dose (5.0-5.5 meq/l) and five of six animals treated with a high dose (7.0-7.5 meq/l). During the infusion of 1.0 mM heptanol, uniform ventricular tachycardia was induced in four of eight animals. Infusion of heptanol, but not potassium, increased the susceptibility to presumably reentrant ventricular tachycardia in normal myocardium. This suggests that agents that affect cellular coupling may have markedly different arrhythmogenic consequences than agents that primarily alter active membrane properties. PMID- 1443194 TI - Prostacyclin rather than endogenous nitric oxide is a tissue protective factor in myocardial ischemia. AB - Nitric oxide (NO) and prostacyclin (PGI2) were determined in effluents of Langendorff-perfused rabbit hearts subjected to 2 h of global low-flow ischemia and subsequent reperfusion. PGI2 release [6-oxo-prostaglandin (PG) F1 alpha] was significantly enhanced during early reperfusion and remained elevated. NO formation was reduced during ischemia but did increase substantially during reperfusion. Indomethacin (3 microM) significantly suppressed ischemia-related 6 oxo-PGF1 alpha and NO release. This was accompanied by severely diminished myocardial recovery. NG-nitro-L-arginine (L-NNA) (100 microM) suppressed NO generation without major effects on 6-oxo-PGF1 alpha generation and cardiac dysfunction but with a remarkable increase in coronary perfusion pressure. These effects of L-NNA were antagonized by L-arginine, whereas the effects of indomethacin were not. There was a substantial loss of creatine kinase specific activity from reperfused ischemic hearts, which was further aggravated by indomethacin but not by L-NNA. These data demonstrate a cardioprotective and endothelium-protective role of PGI2 in myocardial ischemia, which also involves preservation of NO generation. Endogenous NO appears to be important for local regulation of coronary flow. PMID- 1443195 TI - Extracorporeal circuits and autoregulation: effect of albumin coating. AB - Autoregulation of muscle blood flow often is difficult to demonstrate when extracorporeal perfusion is used. This could be caused by contact of blood and foreign material. Accordingly, we tested whether autoregulation is preserved when the system is coated with albumin. Polyurethane tubing between the carotid and distal femoral artery of rats was partially occluded for 1-2 min. With the system uncoated (n = 6 rats) autoregulation was absent. With coated systems (n = 6 rats) the closed-loop gain (Gc) of the apparent autoregulation (0 < Gc < 1) for the pressure range from control (137 +/- 14) to 80 mmHg was 0.40 +/- 0.24 (mean +/- SD). In most cases autoregulation was preceded by a period of "superregulation": after a variable delay flow rose above control. When the distance between occluder and tip of femoral cannula was varied in another group of rats (n = 6), the delay (20-75 s) was linearly related to transit time (10-35 s) of blood. Flow increase thus seemed to be caused by a blood-borne vasodilator originating at the occlusion site and not by a myogenic or metabolic response to decreased pressure and flow. The vasodilator did not originate from the albumin coating. Partial occlusion of an extracorporeal shunt thus can increase flow to the perfused tissue when the system is coated with albumin. The reaction readily disappears when the system is not coated. PMID- 1443196 TI - Hydraulic conductivity of basement membrane with computed values for fiber radius and void volume ratio. AB - The basement membrane contributes to resistance to ultrafiltration of the capillary wall, but efforts to conduct studies of this material have been hindered by difficulty in obtaining homogenous sources and by compression from high filtration pressures. We utilized Matrigel in a conductivity chamber and showed that it reproducibly yielded a specific hydraulic conductivity of (2.247 +/- 0.328) x 10(-14) cm2, which is within 21% of that obtained for porcine glomerular basement membrane by Robinson and Walton (Microvasc. Res. 38: 36-48, 1989). No compression or hysteresis was observed over 5-25 cmH2O pressure difference. Depending on whether data were fit to drag or hydraulic radius fibermatrix models, fiber radius was 0.626-0.696 nm, and void volume ratio varied between 0.826 and 0.846, the former agreeing with the major components of Matrigel. Ready availability of Matrigel, its uniform hydraulic conductivity, and its fit to fibermatrix theory make it ideal to study changes in basement membrane during physiological and pathological changes. Moreover, results of such studies are likely applicable to endothelial barriers, whose luminal and intercellular surfaces are lined with fibrillar materials. PMID- 1443197 TI - Relative responses to luminal and adventitial adenosine in perfused arteries. AB - Responses to luminal and adventitial adenosine were compared in perfused rabbit central ear arteries. Perfused arteries precontracted with 0.5 microM norepinephrine relaxed dose dependently but asymmetrically to luminal and adventitial adenosine. Arteries were more responsive to luminal adenosine in the 0.1- to 1.0-microM range, but they were more responsive to adventitial adenosine at doses > 10 microM. Alternatively, 2-chloroadenosine, a metabolically stable and poorly transported analogue, was equipotent when applied luminally or adventitially. Endothelial damage reduced sensitivity and response asymmetry to luminal and adventitial adenosine. This was consistent with reduced responses to adenosine in luminally rubbed arterial ring segments. Transport inhibition (10 microM dipyridamole) enhanced arterial reactivity to luminal and adventitial adenosine and reduced response asymmetry but was without effect on responses to 2 chloroadenosine. A comparison of the inhibitory effectiveness of adventitial and luminal 8-phenyltheophylline revealed that adventitial antagonist was approximately threefold more effective in inhibiting responses to adventitial adenosine than luminal antagonist (P < 0.05). This "side-dependent" difference was reduced by prolonged antagonist incubation or endothelial removal. The data indicate that adenosine relaxes ear arteries by activation of smooth muscle [half maximum effective concentration (ED50) approximately 11 microM] and endothelial (ED50 approximately 2 microM) receptors. Nevertheless, a sensitive endothelial dependent response does not consistently enhance responses to luminal adenosine in perfused arteries. This appears to be attributable to relative differences in the smooth muscle and endothelium-dependent components of the dilator response and transvascular concentration gradients for luminally and adventitially applied adenosine. A transendothelial diffusion barrier also reduces the ability of luminally applied antagonists to inhibit responses to adventitial adenosine. PMID- 1443198 TI - Reversal by increased CSF [H+] and [K+] of phorbol ester-induced arteriolar constriction in piglets. AB - We determined whether several dilator stimuli could counteract phorbol ester induced constriction of pial arterioles. A closed cranial window was implanted, and the diameter of one pial arteriole was determined by intravital microscopy in newborn pigs. Diameter of one pial arteriole was determined during baseline conditions and topical application of 10(-5) M phorbol 12, 13-dibutyrate (PDB) and during subsequent application of one of the following: arterial hypercapnia (inhalation of 10% CO2), topical application of cerebrospinal fluid with 12 mM K+, or topical application of 10(-5) M isoproterenol in cerebrospinal fluid. PDB constricted the arterioles from 101 +/- 5 to 70 +/- 5 microns (27 +/- 4%; n = 28). During this period of constriction which lasted longer than subsequent interventions (> 90 min), arterial hypercapnia dilated the arterioles by 85 +/- 19% (n = 12), and topical 12 mM K+ dilated the arterioles by 59 +/- 12% and caused vasomotion (n = 7). Despite blockade of direct dilator effects of arterial hypercapnia by indomethacin, arterial hypercapnia still reversed phorbol ester induced constriction, suggesting that acidosis by itself is sufficient to cause this effect. In contrast, topical isoproterenol did not dilate PDB-constricted arterioles (n = 9); however, topical forskolin (2.4 x 10(-7) M) did reverse constriction, implying that protein kinase C activation may interfere with proper functioning of the beta-adrenoceptor. Therefore, increased extracellular fluid levels of K+ and H+, but not isoproterenol, are able to interfere with cerebrovascular consequences of protein kinase C activation. PMID- 1443199 TI - Adenosine improves recovery of postischemic myocardial function via an adenosine A1 receptor mechanism. AB - The effects of adenosine in the nonischemic heart have been shown to be mediated via its binding to extracellular adenosine A1 and A2 receptors located predominantly on myocytes and endothelial cells, respectively. We tested the hypothesis that the beneficial effect of adenosine on postischemic myocardial function is mediated via an adenosine A1 receptor mechanism. Isolated rat hearts perfused at constant pressure (85 cmH2O) were subjected to 30 min of global no flow ischemia (37 degrees C) and 45 min of reperfusion. Hearts treated with adenosine (100 microM) and the adenosine A1 receptor agonist N6 cyclohexyladenosine (CHA; 0.25 microM) recovered 72 +/- 4 and 70 +/- 4% of preischemic left ventricular developed pressures (LVDP), respectively, after 45 min of reperfusion compared with untreated hearts (54 +/- 3% of preischemic LVDP). Adenosine and CHA hearts exhibited greater myocardial ATP contents than control hearts after 10 min of ischemia, but there were no differences in tissue ATP levels after 30 min of ischemia. In contrast, hearts treated with the adenosine A2 receptor agonist phenylaminoadenosine (0.25 microM) failed to demonstrate improved postischemic function (52 +/- 5%). The addition of the A1 selective antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the cardioprotective effect of adenosine (57 +/- 4%). These results suggest that adenosine enhances postischemic myocardial function via an A1 receptor mechanism. PMID- 1443200 TI - Characteristics and origin of myogenic response in isolated mesenteric arterioles. AB - Responses to changes in intravascular pressure of isolated rat mesenteric arterioles were investigated under no-flow conditions. First-, second-, third-, and fourth-generation arterioles were isolated and cannulated. Vascular diameters were measured with an image-shearing device and recorded. The arterioles (except for the first-generation vessels) developed spontaneous tone, corresponding to the step increases in intravascular pressure (from 20 to 160 mmHg, by 20-mmHg steps). For example, at 80 mmHg pressure the mean diameters of first-, second-, third-, and fourth-generation vessels were 286.9 +/- 5.0, 203.4 +/- 8.2, 92.5 +/- 4.6, and 35.6 +/- 4.8 microns, respectively; by use of a Ca(2+)-free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (1 mM) and sodium nitroprusside (SNP; 10(-4) M) the passive diameters of these vessels were 295.6 +/- 6.3, 238.4 +/- 11.7, 120.3 +/- 3.7, and 59.4 +/- 3.1 microns, respectively, demonstrating that the degree of pressure-induced constriction increased with the increasing order of generations (3, 14, 24, and 43%, respectively). The vasoactive function of endothelium and vascular smooth muscle was assessed by the responses of arterioles to acetylcholine (ACh; 10(-6) M) and SNP (10(-7) M) before and after removal of the endothelium with air. After removal of the endothelium, dilation to ACh was abolished while dilation to SNP was retained. Removal of the endothelium did not significantly alter the changes in the diameter of arterioles in response to step increases in intravascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443201 TI - Glycogen depletion-induced lactate reductions attenuate reflex responses in exercising humans. AB - Post leg exercise circulatory arrest (PLE-CA) raises blood pressure (BP) and reduces peak forearm vascular conductance (C). This reflex is evoked by activation of muscle afferents that are often sensitive to lactic acid. We tested the hypothesis that lactic acid reductions induced by muscle glycogen depletion would attenuate the lower-limb metaboreceptor-mediated pressor and forearm vasoconstrictor responses. Eleven subjects had C measured (plethysmography) during post leg exercise circulatory arrest (PLE-CA) (supine bicycle exercise for 9 min, 10 s at 75% VO2max before and after undergoing a glycogen-depletion paradigm (24-h fast followed by 10 min of supine leg exercise at 75% VO2max). In six subjects with lower lactate values, C during PLE-CA was higher after glycogen depletion (0.39 +/- 0.05 vs. 0.21 +/- 0.01 ml.min-1.100 ml-1 x mmHg-1; P < 0.01) and BP was lower (113 +/- 6 vs. 128 +/- 6 mmHg, P < 0.01). In five subjects without attenuated lactate responses, C and BP during PLE-CA were not different. Muscle biopsies (n = 5) demonstrated that the paradigm lowered muscle glycogen concentrations. Thus glycogen depletion-induced reductions in muscle lactate are associated with reduced muscle metaboreceptor-mediated responses. PMID- 1443202 TI - Sarcolemmal Na(+)-Ca2+ exchange activity and exchanger immunoreactivity in developing rabbit hearts. AB - It has been postulated that as a consequence of an underdeveloped sarcoplasmic reticulum, sarcolemmal Na(+)-Ca2+ exchange assumes relatively greater importance in modulating Ca2+ fluxes in the developing heart. To explore this concept, cardiac sarcolemmal vesicles were prepared from late fetal (28-day gestation), newborn (24-48 h), immature (14-16 days), and adult New Zealand White rabbits. Na(+)-dependent Ca2+ uptake was measured by diluting Na(+)-loaded (140 mM) vesicles into Na(+)-free buffer and measuring 45Ca2+ uptake (40 microM Ca2+) by timed quenching and rapid filtration. Vesicles from all four age groups demonstrated Ca2+ uptake curves characteristic of Na(+)-Ca2+ exchange with stimulation by valinomycin and inhibition by amiloride. Initial uptake velocity (measured at 2 s and corrected for the fraction of competent vesicles) was significantly higher in fetal (23.2 +/- 5.5 nmol/mg) and newborn (26.2 +/- 5.9 nmol/mg) than in adult sarcolemmal preparations (7.3 +/- 1.2 nmol/mg). Uptake was intermediate in the 2-wk-old group (13.7 +/- 1.7 nmol/mg). The relative amounts of exchanger protein were compared by quantitating immunoreactivity using a polyclonal antibody to the Na(+)-Ca2+ exchanger. Densitometric scanning of protein slot blots demonstrated approximately 2.5 times more exchanger protein in fetal and newborn sarcolemma than in adult preparations. The relative amount of exchanger protein detected immunologically corresponded with the age-related differences observed in exchanger activity. Thus the cardiac sarcolemmal Na(+) Ca2+ exchanger is abundant and functionally well-developed in the late fetal/early newborn rabbit heart and appears to decline postnatally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443203 TI - Development of cardiac innervation, ventricular fibrillation, and sudden infant death syndrome. AB - The effects of bilateral vagotomy and of right, left, and bilateral stellectomy on sinus node and on ventricular fibrillation threshold (VFT) were assessed in three groups of puppies (1, 3, and 5 wk old) and one group of adult dogs. Heart rate was increased by vagotomy and reduced by right stellectomy in all groups. After vagotomy, VFT did not change in the first week, while it decreased in the third week (-21%, P < 0.0001), in the fifth week (-20%, P < 0.001) and in the adults dogs (-18%, P < 0.005). VFT was not modified by right stellectomy in the first week and in the fifth week (0%, NS), while it decreased in the third week ( 28%, P < 0.05) and in the adults (-32%, P < 0.001). Left stellectomy, performed after right stellectomy, increased VFT in the third week (+52%, P < 0.05), in the fifth week (+62%, P < 0.001), and in the adults (+45%, P < 0.01). Thus removal of either vagal or right cardiac sympathetic activity increases susceptibility to ventricular fibrillation already during the first weeks of life. By contrast, removal of left sympathetic nerves increases cardiac electrical stability. These findings are consistent with the hypothesis that a developmental abnormality in cardiac innervation may play a role in the genesis of some cases of sudden infant death syndrome. PMID- 1443204 TI - Baroreflex regulation of forearm vascular resistance after exercise in hypertensive and normotensive humans. AB - The mechanisms underlying the antihypertensive period following a bout of exercise are not well understood. We examined the aftereffects of exercise on the linear relationship between forearm vascular resistance (FVR) and estimated central venous pressure (CVP) during leg raising and lower body negative pressure to determine whether an alteration of the baroreflex control of FVR was associated with the decreased blood pressure. Blood pressure, forearm blood flow (FBF), and estimated CVP were obtained in 13 hypertensive and 9 normotensive subjects evaluated in a randomized crossover fashion after 30 min of cycle ergometer exercise and after a nonexercise control period. In hypertensive subjects, the reduced blood pressure was accompanied by an increased baseline FBF after exercise. This resulted in a downward shift of the FVR-CVP relationship, while the slope was unchanged. In normotensive subjects, blood pressure and baroreflex control of FVR were unaffected by prior exercise. Four of the hypertensive subjects performed an additional study in which forearm skin was vasodilated with local heating to FVR levels similar to those observed after exercise. Results suggested that the aftereffects of exercise could not be attributed to changes in cutaneous blood flow. We speculate that modulation of the baroreflex control of FVR after exercise contributes to its antihypertensive effect. PMID- 1443205 TI - K+ATP-channel activation causes marked vasodilation in the hypertensive neonatal pig lung. AB - We studied the potential role of ATP-sensitive potassium (K+ATP) channel activation in mediating pulmonary vasodilation in newborn piglets. Piglet lungs (n = 14, ages 1-4 days) were artificially perfused with recirculating Ringer solution containing bovine serum albumin and statistically inflated using 95% O2 5% CO2. We measured pulmonary arterial pressure (Ppa) and distribution of pulmonary vascular resistance (using double-occlusion method). Under resting conditions (Ppa 13.7 +/- 1.6 cmH2O, mean +/- SE), the K+ATP channel agonist BRL 38227 (lemakalim, 10(-7) and 10(-6) M) caused small dose-dependent pulmonary vasodilation. This response was diminished by the K+ATP-channel blocker glibenclamide (10(-5) M). Pretreatment of lungs with indomethacin (10(-5) M) and N omega-nitro-L-arginine (10(-5) M) to inhibit cyclooxygenase- and nitric oxide (NO)-related vasodilation, respectively, resulted in a marked increase in the baseline Ppa to 85.6 +/- 11.2 cmH2O. Injection of BRL 38227 (10(-7) M and 10(-6) M) in these lungs decreased Ppa to 72.5 +/- 8.5 (P < 0.01) and 19.3 +/- 0.9 cmH2O (P < 0.01), respectively; the corresponding times for half-recovery of Ppa (t1/2R) were 5.7 +/- 4.3 and > 20 min. Glibenclamide (10(-5) M) abolished the response to 10(-7) M BRL 38227 and significantly diminished (P < 0.05) the decreases in Ppa and t1/2R in response to 10(-6) M BRL 38227 but not to acetylcholine (10(-10) M). We conclude that activation of K+ATP channels has a minimal role in maintaining basal pulmonary vasomotor tone but is able to induce marked vasodilation when NO and cyclooxygenase-dependent vasodilatory mechanisms are inhibited. PMID- 1443206 TI - Aortic perfusion pressure as early determinant of beta-isomyosin expression in perfused hearts. AB - Pressure overload in vivo induces an increase in cardiac protooncogene and stress protein expression that may initiate the long-term genetic changes observed in hypertrophy. To known whether mechanical stimulus is linked to specific gene transcription, expression of immediate early genes and synthesis of total proteins and myosin heavy chains (MHCs) were studied in beating and KCl-arrested isolated rat hearts perfused for 2 h under various coronary pressures. The main result of this study is that in the beating heart an augmentation of aortic pressure from 60 to 120 mmHg results in a pronounced enhancement of the synthesis of MHC (+59%) and of the expression of the beta-MHC isomyosin mRNA (iso-mRNA; +104%). Also, total protein synthesis and the amounts of poly-(A)+, c-fos, c-myc, and heat-shock protein HSP68 mRNAs were increased. To arrest the heart at 60 mmHg has no effect on total protein synthesis and on the amounts of poly(A)+, alpha MHC and beta-MHC iso-mRNAs, and mRNAs coding for oncoproteins, but the synthesis of MHC decreased by 24%. By contrast with what we have observed in the beating heart, the augmentation of the coronary pressure in the arrested heart stimulates total protein synthesis and increases the amount of poly(A)+, c-fos, c-myc, and HSP68 mRNAs but has no effect on the expression of both MHC iso-mRNAs. In conclusion, the activation of myosin synthesis by high coronary pressure in this model has mainly a pretranslational origin when the heart is beating.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443207 TI - Left ventricular dimensions during hemorrhagic shock measured by biplane cinefluorography. AB - The effects of hemorrhagic shock on left ventricular dimensions and volume were studied in 15 splenectomized dogs. A 42 +/- 1% decrease in total blood volume caused arterial blood pressure to fall 60% (from 120 +/- 5 to 48 +/- 3 mmHg); the first derivative of left ventricular pressure at a developed pressure of 40 mmHg fell 54% (from 1,930 +/- 94 to 905 +/- 93 mmHg/s, P < 0.05). Cardiac output fell 76% due to a 73% decrease in stroke volume; heart rate was unchanged at the end of hemorrhage but increased 50% during 3 h of sustained shock (from 110 +/- 6 to 166 +/- 8 beats/min, P < 0.05). During hemorrhage the septal-lateral and the anterior-posterior end-diastolic dimensions fell to a greater extent (7.8 mm, 21% and 7.0 mm, -18%, respectively) than the apex-base dimension (2.3 mm, -3.3%, P < 0.05). As a result of these dimensional changes, left ventricular end diastolic volume fell 39% (from 48 +/- 2 to 28 +/- 1 cm3, P < 0.01). End-systolic dimensions fell in the same proportion during hemorrhage, resulting in a 30% decrease in end-systolic volume (from 30 +/- 2 to 21 +/- 1 cm3, P < 0.05). After 120 min of sustained shock, all end-diastolic dimensions remained unchanged, but end-systolic dimensions and volume increased significantly from values measured at end hemorrhage (P < 0.05), causing ejection fraction and stroke volume to fall to a greater extent. This study confirms a pronounced reduction in the minor axes of the left ventricle during hemorrhagic shock with subsequent reduction in ventricular function. PMID- 1443208 TI - Tonic sympathetic excitation and vasomotor control from pontine reticular neurons. AB - The pontine reticular formation (PRF) was explored for regions providing tonic control of arterial pressure, heart rate, and activity of sympathetic nerves. In Saffan (alfaxalone-alfadolone)-anesthetized rats, discharge of neurons in the PRF or rostral ventrolateral medulla (RVLM) was inhibited by microinjections of glycine (1 M; 65 +/- 2 nl). PRF blockade caused large, short-lasting (116 +/- 17 s) decreases in arterial pressure and equal decreases in renal (-47 +/- 4%) and splenic (-45 +/- 4%) nerve activity, indicating that PRF neurons contribute to resting control of vasomotor discharge. In contrast, RVLM blockade caused long lasting (41 +/- 3 min) decreases in arterial pressure and unequal decreases in activity of renal (-50 +/- 4%) and splenic (-31 +/- 6%) nerves. The short duration of the responses to PRF blockade could not be attributed to compensation by baroreceptors or by actions specific to glycine. Excitation of PRF neurons with amino acids caused increases as well as decreases in arterial pressure and sympathetic activity, and therefore activated neurons distinct from those that are tonically active. These results identify a source of cardiovascular control in the reticular formation of the pons that provides tonic excitatory drive to sympathetic nerves and that differs from the well-known source in the RVLM. PMID- 1443209 TI - Chronic administration of cardiovascular drugs: altered energetics and transmembrane signaling. AB - The effects of clinically used cardioactive agents in furazolidone-induced cardiomyopathy in the turkey poult have been recently reported, and note-worthy differences in cardioprotective efficacy of adrenergic effectors, calcium channel blockers, and cardiac glycosides have been noted in animal and human studies of heart failure. We therefore investigated the effects of chronic oral administration of cardioactive agents on ventricular tissue from normal turkey poults, and we determined whether these agents altered cardiac function, energetics, or transmembrane signaling pathways in a manner that might contribute to the varying degrees of cardioprotection and therapeutic efficacy reported previously. Creatine content was significantly higher in propranolol- and atenolol-treated animals. There was also higher lactate dehydrogenase and creatine kinase activities, reflecting an overall increase in energy reserve. Treatment with the calcium channel antagonists verapamil and nifedipine produced a significant increase in adenylyl cyclase activity and beta-adrenergic receptor density. Nifedipine treatment resulted in upregulation of both beta-adrenergic receptors and dihydropyridine receptors. This finding was associated with enhanced peak twitch force at all extracellular Ca2+ concentrations. We demonstrate for the first time that clinically used pharmacological agents (nifedipine and propranolol) result in alteration in two transmembrane signaling pathways, with associated alterations in physiological performance. Moreover, agents without cardioprotective effect in furazolidone-induced cardiomyopathy did not induce alterations in transmembrane signaling or energetics in normal hearts. PMID- 1443210 TI - Absence of right ventricular isovolumic relaxation in open-chest anesthetized dogs. AB - During the left ventricular (LV) pump cycle, peak negative first derivative of pressure vs. time (dP/dt) occurs very close to the end of LV ejection, and there is a well-defined isovolumic relaxation period. Despite similarities between the right ventricular (RV) and LV pump cycles, recent studies indicate uncertainty as to whether peak negative RV dP/dt occurs simultaneously with RV end ejection and whether there is an isovolumic relaxation period during the RV pump cycle. To study these questions, we recorded relative timing of peak negative RV dP/dt, RV end ejection, and right atrial-RV pressure crossover in the open-chest anesthetized dog. The data demonstrate that peak negative RV dP/dt occurs an average of 60 ms before end ejection and that there is no RV isovolumic relaxation period. These findings have implications for the possible use of peak negative RV dP/dt as a marker of RV end ejection and for how time constants of pressure decay obtained during RV relaxation can be interpreted. PMID- 1443211 TI - Neural mechanisms regulating neurohypophysial resistance arteries. AB - We defined the extent of vasoactive intestinal polypeptide (VIP) and noradrenergic influences on isolated 100- to 200-microns-diameter vessels from the resistance arterial circulation of the neurohypophysis. A dual extracranial (inferior hypophysial) and intracranial (superior hypophysial) arterial supply to the neurohypophysis was confirmed. The inferior hypophysial artery demonstrates noradrenergic and VIP-like perivascular nerves, whereas the superior hypophysial artery shows primarily VIP-like innervation. Pharmacological sensitivity of the inferior hypophysial to VIP [mean effective dose (ED50) = 10(-8.2) M] and to norepinephrine (ED50 = 10(-5.7) M) was demonstrated. The superior hypophysial reacted only to VIP (ED50 = 10(-8.6) M). The physiological relevance of these findings was tested with transmural nerve stimulation. Frequency-dependent vasodilation of both inferior and superior hypophysial arteries was demonstrated. This dilation could not be blocked with atropine or propranolol. Frequency dependent vasoconstriction was identified in extracranial vessels including the inferior hypophysial artery. This constriction is only partially blocked by prazosin, phentolamine, and guanethidine. When neurohypophysial resistance vessels are compared with larger circle of Willis arteries and similar-size pial vessels of other cerebral regions, they appear to have regionally unique neural mechanisms for regulating blood flow. Specifically whether controlled by periarterial nerves or other tissue influences, the inferior hypophysial artery appears to meet anatomic, pharmacological, and physiological definitions of neural control for both dilator and constrictor activities of flow to the neurohypophysis. PMID- 1443212 TI - An angiographic method for in vivo study of arteries of the circle of Willis in small animals. AB - An X-ray imaging technique designed to allow sequential diameter measurements of the cerebral vessels in intact, anesthetized small animals under relatively physiological conditions is described. The ferret and the rabbit were chosen as potentially useful animal models for studying the cerebrovascular system because of the advantageous anatomic characteristics of these relatively small species. A commercially available and relatively inexpensive X-ray imaging system with a small focal spot provides good spatial resolution. An external carotid perfusion loop allows for 1) the introduction of low-osmolality contrast medium without changing perfusion pressure or flow and 2) measurement of internal carotid and circle of Willis pressures at the same time that the vessel images are obtained. In the present study, detection of small changes in the diameters of the small vessels is facilitated by an algorithm utilizing the X-ray absorption by the entire vessel cross section. This avoids some of the problems of edge detection for small cylindrical vessels wherein the contrast is less than optimal and diminishes as the vessel perimeter is approached. PMID- 1443213 TI - Suction effusion fluid from skin and constituent analysis: new candidate for interstitial fluid. AB - The authors analyzed the constituents of effuse transcutaneous fluid, labeled suction effusion fluid (SEF), and monitored its glucose concentration during glucose loading in rabbits (Japan White, female) under pentobarbital anesthesia. The SEF was sampled by suctioning corneal layer-stripped skin at 400 mmHg absolute pressure. The SEF proved to have nearly the same concentrations as serum for lower-molecular-weight substances such as glucose, creatinine, and urea nitrogens, but not for higher-molecular-weight substances such as serum proteins. The SEF protein concentration was one-fourth that of serum protein. Proteins > 100 kDa molecular mass were barely detectable in the SEF. Monitoring of SEF glucose change every 10 min during intravenous glucose loading was successfully accomplished, and SEF glucose concentration followed blood glucose concentration with a 10-min delay. The SEF was thought to consist of interstitial fluid and/or effuse fluid from small vessels in subcutaneous tissue. PMID- 1443214 TI - L-arginine decreases infarct size caused by middle cerebral arterial occlusion in SHR. AB - L-Arginine, but not D-arginine, serves as a precursor for the synthesis of nitric oxide (NO), a potent dilator of cerebral blood vessels. We examined the effects of administering L-arginine (300 mg/kg ip) on the volume of infarction in two models of focal cerebral ischemia in spontaneously hypertensive rats (SHR). L Arginine was administered before (16 and 3 h) and after (5 min and 2 h) vessel occlusion, and animals were killed 24 h later. L-Arginine treatment decreased infarct size in rats subjected to distal middle cerebral arterial (MCA) plus ipsilateral common carotid arterial (CCA) occlusion by 31% [147 +/- 12 (saline) vs. 101 +/- 9 mm3 (L-arginine), P < 0.05]. D-Arginine, administered according to the same dosage and protocol, was without effect. In the group subjected to proximal MCA occlusion, L-arginine decreased infarction size in the striatum by 28% [47 +/- 5 (saline) vs. 34 +/- 3 mm3 (L-arginine), P < 0.05] and neocortex by 11% [193 +/- 7 (saline) vs. 171 +/- 8 mm3 (L-arginine), P < 0.05]. Changes in blood pressure or other measured physiological parameters did not account for the observed differences. The possible use of L-arginine for the treatment of focal cerebral ischemia merits further investigation. PMID- 1443215 TI - Characterization of norepinephrine-stimulated protein synthesis in rat brown adipocytes. AB - Rat brown adipocytes were incubated for 24 h with or without norepinephrine (NE) in Dulbecco's modified Eagle's medium with albumin, calf serum, and antibiotics. Brown fat cells were viable as defined by unchanged cell morphology, ATP content, or basal and NE-stimulated respiration. However, a 24-h exposure to NE led to a decline in NE-stimulated respiration that was not due to loss of thermogenic capacity. Brown fat cells incubated with or without NE had similar protein, succinate dehydrogenase, and uncoupling protein (UCP) content. These results differ from those observed after food deprivation in rats where loss of mitochondrial proteins occurs within 24 h, suggesting that reduced exposure to NE is not the only factor responsible for brown fat atrophy. NE increased [35S]methionine incorporation into cellular proteins, mitochondrial proteins, and UCP. The effect of NE on cell protein synthesis was inhibited by propranolol but not by prazosin. It was also inhibited 95% by cycloheximide but only partially (50%) by actinomycin D in contrast to NE stimulation of UCP labeling, which required RNA transcription. Chloramphenicol-sensitive protein synthesis was stimulated by NE. These results indicate a trophic action of NE in brown adipocytes exerted both at the level of RNA transcription and translation. PMID- 1443216 TI - Duodenal preabsorptive origin of gustatory alliesthesia in rats. AB - Facial consummatory responses reflecting ingestive and aversive perceptions were studied and quantified in rats chronically implanted with gastric, duodenal, and oral catheters. A gustatory stimulus of 50 microliters of 1.75 mol/l sucrose was injected into the mouth every 5 min for 65 min. At time 0, 0.5 ml containing 0.3 g glucose was injected into the stomach or into the duodenum. Typical ingestive facial consummatory responses were observed in response to sweet stimuli prior to the load. Aversive consummatory responses were observed in response to sweet stimuli after the glucose duodenal load (negative alliesthesia). The gastric load of glucose was not followed by negative alliesthesia in response to sweet oral stimuli. In the last part of the experiment the rats were vagotomized. When the rats were subjected again to the same gustatory sessions, the duodenal load was followed by weak and delayed negative alliesthesia in response to sweet stimuli. These results in rats parallel results obtained in human subjects and reinforce the hypothesis of the existence of a duodenal preabsorptive signal for alimentary alliesthesia. They also suggest that the vagus nerve plays a part in the perception of satiety. PMID- 1443217 TI - Kinetic heterogeneity of Na-D-glucose cotransport in teleost gastrointestinal tract. AB - D-[3H]glucose transport properties of brush-border membrane vesicles (BBMV) of upper intestine and pyloric ceca of the Pacific copper rockfish (Sebastes caurinus) were characterized and compared. Vesicles from both organs exhibited Na dependent, phloridzin-sensitive, carrier-mediated transport systems. Kinetic constants for D-[3H]glucose influx across vesicle membranes were as follows: upper intestine, apparent affinity of glucose (Kt) = 0.14 +/- 0.02 mM, maximal glucose influx (JM) = 1,649 +/- 57 pmol.mg protein-1.10 s-1; pyloric ceca, Kt = 0.58 +/- 0.12 mM, JM = 2,439 +/- 178 pmol.mg protein-1.10 s-1. A hyperbolic relationship, following Michaelis-Menten kinetics, occurred between D-glucose influx and external Na concentration for pyloric ceca, while a sigmoidal function, following Hill cooperativity kinetics (n = 1.71 +/- 0.31), was disclosed between the variables for the intestine. External phloridzin, D glucose, methyl alpha-D-glucopyranoside, and D-galactose were the most potent inhibitors of D-[3H]glucose influx in each organ. Other compounds were generally more inhibitory in vesicles from the pyloric cecum than those of the intestine except for D-mannose which was considerably more potent in the intestine. Results suggest that there may be proximal-to-distal hexose- and Na-binding gradients in the teleost gut for optimizing sugar absorption during passage of food through the gastrointestinal tract. PMID- 1443218 TI - Pulmonary vascular response to anaphylaxis in isolated canine lungs. AB - We determined changes in vascular resistance and microvascular permeability during anaphylactic reaction in isolated canine lungs perfused at constant pressure with autologous blood. In lungs with anaphylaxis induced by an intra arterial injection of Ascaris suum antigen (10 mg), pulmonary vascular resistance and capillary pressure assessed as double occlusion pressure increased transiently by 10 times and 6.3 mmHg, respectively. Pre- to postcapillary vascular resistance ratio decreased from 0.89 +/- 0.05 to 0.21 +/- 0.06, suggesting predominant pulmonary venoconstriction. In lungs perfused in the antidromic direction from the pulmonary vein to the artery, anaphylaxis caused marked precapillary vasoconstriction, consistent with pulmonary venoconstriction. Vascular permeability assessed using the capillary filtration coefficient and isogravimetric capillary pressure did not change significantly for 3 h in either group. No changes were found in any variables in the saline-injected control lungs. The final weight of the anaphylactic lungs was significantly greater than that of the control lungs. Thus we conclude that anaphylaxis in isolated canine lung produces an increase in capillary pressure due to pulmonary venoconstriction without significant changes in vascular permeability. Pulmonary edema accompanied by anaphylactic hypotension may result from an increase in pulmonary hydrostatic intravascular pressure but not an increase in pulmonary vascular permeability. PMID- 1443219 TI - Sex differences in central cholinergic and angiotensinergic control of vasopressin release. AB - In conscious, unrestrained rats, the intracerebroventricular injection of the cholinergic agonist, carbachol, or angiotensin II resulted in the transient stimulation of vasopressin secretion, elevation of mean arterial blood pressure, and reduction of heart rate. After the injection of carbachol (25 ng) into a lateral cerebral ventricle, the plasma vasopressin concentration in male rats was increased to twice that of female rats in each phase of the estrous cycle; mean arterial blood pressure was elevated more in males than females, whereas heart rate fell to the same extent in both sexes. In contrast, the increase in the plasma vasopressin concentration of males after the injection of angiotensin II (20 ng) was one-half that of females, and the hypertensive and bradycardic responses were similar in both sexes. Phase of the female estrous cycle had no effect on the responses to either agent. These findings indicate that central cholinergic and angiotensinergic mechanisms controlling vasopressin release are influenced differently by gender. The role of the gonadal steroid hormones in these mechanisms remains to be determined. PMID- 1443220 TI - Heparin suppresses endothelin-1 action and production in spontaneously hypertensive rats. AB - Previous studies have shown that chronic subcutaneous administration of heparin significantly reduces blood pressure in hypertensive rats. The intracellular mechanisms of how heparin prevents smooth muscle cell proliferation remain unclear. This study was designed to examine whether heparin affects endothelin-1 action and production, to further elucidate the mechanism of the antihypertensive effect of heparin. Four-week treatment with heparin (300 U/day sc) significantly decreased blood pressure in spontaneously hypertensive rats (SHR; 199 +/- 8 vs. 164 +/- 9 mmHg; P < 0.001) and completely blunted pressor response to endothelin 1 in SHR. Heparin treatment did not decrease blood pressure response nor did it attenuate blood pressure responses to endothelin-1 in Wistar-Kyoto rats (WKY). Heparin significantly suppressed endothelin-1-induced increase in intracellular calcium concentration and inositol 1,4,5-trisphosphate level in cultured vascular smooth muscle cells in a dose-dependent manner and endothelin-1 release from cultured endothelial cells. These inhibitions were significantly more pronounced in SHR than in WKY. In conclusion, our findings indicate that the antihypertensive effect of heparin is mediated, at least in part, by the inhibition of endothelin-1 action on vascular smooth muscle cells and endothelin 1 production from endothelial cells. PMID- 1443221 TI - Morphological and physiological correlates with swimming performance in juvenile largemouth bass. AB - Winter- and summer-acclimatized largemouth bass (Micropterus salmoides) were collected from hatchery ponds in eastern Colorado during late winter and midsummer, then challenged with two prolonged swimming performances (step test and constant-velocity endurance). Variation in the step test performances was significantly correlated with variation in the endurance performances in the winter-acclimatized but not in the summer-acclimatized fish. Fourteen physiological and morphological traits were measured on each fish, and correlations among these traits and swimming performance were tested. None of the traits measured were correlated with performance variation in both the winter- and summer-acclimatized fish. The only significant correlate with swimming performance in the summer-acclimatized fish was white muscle lactate dehydrogenase activity (n = 19). Six of the seven factors correlating with winter swimming performance (n = 18-19) could be divided into two categories: traits associated with fasting (condition factor and liver enzymatic activity) and those associated with oxygen delivery (heart mass, heart and red muscle cytochrome oxidase activity). The results of this study suggest that morphological and physiological correlates of swimming performance in juvenile largemouth bass are profoundly influenced by seasonal variation. PMID- 1443222 TI - Cardiovascular responses to nasal water flow in rats are unaffected by chemoreceptor drive. AB - Peripheral chemoreceptors generally play a limited role in the initial development of diving bradycardia in mammals. However, T.F. Huang and Y.I. Peng (Jpn. J. Physiol. 26: 395-401, 1976) reported that peripheral chemoreceptors are very important for manifestation of the diving response in conscious rats. The objectives of this study were to reinvestigate those findings and determine whether the cardiovascular responses to simulated diving in the rat were potentiated during preexisting hypoxia or hypercapnia. Responses to simulated diving were elicited by nasal water flow with concurrent apnea in paralyzed, artificially ventilated Sprague-Dawley rats anesthetized with Innovar. The experiments show that nasal stimulation in the rat results in rapid bradycardia and hypotension and that these responses are not due to laryngeal stimulation. The data also suggest that chemoreceptors do not play a role in the initiation of the responses to simulated diving in rats and that preexisting chemoreceptor drive does not alter the cardiovascular responses. Additionally, we found that concomitant expiratory apnea is necessary to sustain the profound initial cardiovascular changes induced by nasal water flow. PMID- 1443223 TI - Membrane and synaptic activity during anoxia in the isolated turtle cerebellum. AB - Electrical depression in the turtle brain during anoxia has been suggested as a strategy for sparing energy and promoting the extraordinary survival capacity of this tissue. The present study was aimed toward defining the changes in membrane properties during anoxia that may underlie such electrical depression. Studies were conducted in isolated cerebellum from turtle brain. Anoxia caused transmembrane potentials (TMP) to become relatively less polarized in most Purkinje cells. In no cell, however, was TMP depolarized to levels associated with the complete loss of transmembrane ion gradients produced by tissue superfusion with iodoacetate during anoxia. Sodium (and likely calcium) spike thresholds were increased, postsynaptic responses from the major afferent input pathways to Purkinje cells were depressed, and input resistance decreased significantly during anoxia. These changes likely contribute to the sparing of energy needed for ion transport and perhaps other functions that may be directly related to cell survival. PMID- 1443224 TI - Renal medullary interstitial infusion of diltiazem alters sodium and water excretion in rats. AB - The role of renal papillary blood flow in regulation of fluid and electrolyte excretion was examined. The effects of an acute infusion of diltiazem (5 micrograms.kg-1 x min-1) into the renal medullary interstitium on papillary blood flow and sodium and water excretion were studied. Changes of renal blood flow were measured using an electromagnetic flow probe. Cortical and papillary blood flows were measured using laser-Doppler flowmetry. Renal and cortical blood flows were unchanged during medullary interstitial infusion of diltiazem, but papillary blood flow increased 26% (P < 0.05) and remained elevated for 1 h after diltiazem infusion was discontinued. Glomerular filtration rate (GFR) of the infused kidney increased by 21% from a control of 1.0 +/- 0.1 ml.min-1 x g-1 during infusion of diltiazem (P < 0.05), but it returned to control after diltiazem infusion was stopped. Urine flow and sodium excretion increased by 70% (P < 0.05), and fractional sodium excretion rose from 1.5 +/- 0.2 to 2.4 +/- 0.3% of the filtered load during the hour after diltiazem infusion. Renal blood flow, cortical and papillary blood flow, GFR, urine flow, and sodium excretion in the 0.9% sodium chloride vehicle-infused kidney were not significantly altered during the experiment. Intravenous infusion of the same dose of diltiazem (5 micrograms.kg-1 x min-1) increased GFR by 22%, but had no effect on urine flow and sodium excretion. These results indicate that renal medullary interstitial infusion of diltiazem selectively increased renal papillary blood flow, which was associated with an increase of sodium and water excretion. PMID- 1443225 TI - Role of right heart receptors in the control of renin, vasopressin, and cortisol secretion in dogs. AB - We have reported that increased left heart pressure inhibits increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol during arterial hypotension. The goal of this study was to determine whether increases in right heart pressure also inhibited hormonal responses to hypotension. Seven dogs were chronically instrumented with inflatable cuffs around the ascending aorta (AA), the pulmonary artery (PA), and the thoracic inferior vena cava (IVC), as well as with catheters in both atria, the abdominal aorta, and vena cava. The IVC, the PA, and the AA cuffs were inflated on different days to cause step reductions in mean arterial pressure (MAP) of 5, 10, 20, and 30% below control MAP. Graded constriction of the AA caused large increases in left atrial pressure and plasma atrial natriuretic peptide (ANP), but had no effect on plasma AVP or cortisol and caused only a small increase in PRA at the maximal reduction of MAP. Constriction of the IVC reduced both atrial pressures and plasma ANP, but stimulated increases in PRA, AVP, and cortisol. Constriction of the PA increased right atrial pressure and plasma ANP and caused increases in plasma AVP and cortisol that were similar to responses during IVC constriction, but the PRA response was only half (P < 0.05). These results indicate that increasing pressure on the right side of the heart can attenuate the PRA response to hypotension, and suggest that the inhibition is mediated by the rise in plasma ANP. PMID- 1443226 TI - Growth hormone-releasing hormone antibodies suppress sleep and prevent enhancement of sleep after sleep deprivation. AB - Previous reports suggest that the hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep, especially non-rapid-eye-movement sleep (NREMS). To evaluate the role of endogenous GHRH in sleep regulation, the effects of antibodies to rat GHRH (GHRH-ab) were studied on normal sleep, brain temperature (Tbr), and GH secretion in experiment I and on enhanced sleep after sleep deprivation in experiment II. In experiment I, affinity-purified GHRH-ab (50 and 200 micrograms) raised in goats and a control goat immunoglobulin G (IgG) preparation were injected intracerebroventricularly (icv) in rats 1 h before the onset of the light cycle, and sleep-wake activity and Tbr were recorded for the next 12 or 23 h. Both doses of GHRH-ab suppressed NREMS and REMS throughout the light cycle. Sleep durations at night were normal. Electroencephalographic (EEG) slow-wave activity, characterized by EEG slow-wave amplitudes, was reduced after GHRH-ab during both the light and the dark cycles. Plasma GH concentrations measured 6-12 h after injection of GHRH-ab (200 micrograms) were diminished. Both the control IgG and GHRH-ab elicited fever. In experiment II, the sleep-wake activity and Tbr of rats were recorded for 24 h in three experimental conditions: base-line with icv injection of IgG, 3-h sleep deprivation with icv IgG injection, and 3-h sleep deprivation with icv GHRH-ab (200 micrograms). After sleep deprivation (+IgG), a prompt increase in EEG slow-wave activity (power density analysis) and late increases in NREMS and REMS durations were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443227 TI - Exercise-induced cellular alterations in the diaphragm. AB - Limited data exist concerning the effects of exercise training on cellular oxidative capacity in the diaphragm of senescent animals. In this study we examined the changes in cellular oxidative capacity, muscle cell cross-sectional area (CSA), and capillarity within the costal diaphragm of senescent animals after a 10-wk endurance-training program. Twelve 24-mo-old female Fischer 344 rats were divided into either a sedentary control group (n = 6) or exercise training group (n = 6). The trained animals exercised on a motor-driven treadmill (60 min/day, 5 days/wk) at a work rate equal to approximately 55-65% VO2max. Capillaries were identified histologically and fiber types determined using adenosinetriphosphatase (ATPase) histochemistry. Succinate dehydrogenase (SDH) activity and CSA in individual fibers were measured using a computerized image analysis system. Exercise training did not increase (P > 0.05) the capillary-to fiber ratio for any fiber type. However, training significantly decreased CSA (P < 0.05) and increased capillary density (capillary number/CSA) (P < 0.05) in type I, type IIa, and type IIb fibers. Furthermore, exercise training resulted in small but significant increase in SDH activity (P < 0.05) in type I and IIa fibers, whereas training did not alter SDH activity (P > 0.05) in type IIb fibers. These data demonstrate that endurance training in senescent animals results in small relative improvements in both oxidative capacity and capillary density in costal diaphragmatic type I and IIa muscle fibers. The increase in both capillary density and fiber SDH activity was largely due to a reduction in fiber CSA. PMID- 1443228 TI - Effects of aging on entrainment and rate of resynchronization of circadian locomotor activity. AB - The phase angle of entrainment of the circadian rhythm of the locomotor activity rhythm to a light-dark (LD) cycle was examined in young (2-5 mo old) and middle aged (13-16 mo old) hamsters. An age-related phase advance in the onset of locomotor activity relative to lights off was seen during stable entrainment to a 14:10-h LD cycle. In addition, the effects of age on the rate of reentrainment of the circadian rhythm of locomotor activity were examined by subjecting young and middle-aged hamsters to either an 8-h advance or delay shift of the LD cycle. Middle-aged hamsters resynchronized more rapidly after a phase advance of the LD cycle than did young hamsters, whereas young hamsters were able to phase delay more rapidly than middle-aged hamsters. The age-related phase advance of activity onset under entrained conditions, and the alteration of responses in middle-aged hamsters reentraining to a phase-shifted LD cycle, may be due to the shortening of the free-running period of the circadian rhythm of locomotor activity with advancing age that has previously been observed in this species. PMID- 1443229 TI - Irradiance responsivity and unequivocal type-1 phase responsivity of rat circadian activity rhythms. AB - Behavioral, neuropharmacological, and molecular studies of light-induced phase shifting of rodent circadian rhythms evaluate carefully the phase dependence of light responsivity. However, much less information is available regarding the dependence of such effects on the duration and irradiance of the photic stimulus used. In this study, very brief (5-min) white light pulses of 50 microW/cm2 (175 lux) administered to hooded rats elicited unequivocal type-1 phase responsivity, without significant changes in period, and with phase shift variability comparable to that in studies using longer, higher intensity pulses. Irradiance dependence was demonstrated in the phase-delay, phase-advance, and crossover portions of the phase-response curve, with minimal phase shifting seen during the dead zone even at very high irradiance. These results indicate that maximal phase shifting magnitude may be achieved with shorter, less intense photic stimuli than are often used in studies of the neural mechanisms involved in light responsivity of rat circadian rhythms. PMID- 1443230 TI - Influenza virus-induced changes in rabbit sleep and acute phase responses. AB - Systematic investigations of sleep after viral inoculation have not previously been described. In the present study, rabbits were inoculated intravenously (iv) with control allantoic fluid followed by two sequential inoculations of influenza virus at intervals of 24 h. After each i.v. inoculation, sleep and brain temperature (Tbr), as well as leukocyte distributions and serum levels of antiviral activity and ceruloplasmin, were monitored. The first viral inoculation elicited several acute phase responses, including increased non-rapid-eye movement sleep (NREMS), Tbr, serum antiviral activity, and serum ceruloplasmin levels, as well as neutrophilia and lymphopenia. In contrast to the effects of the first inoculation, after the second inoculation of virus, all these acute phase parameters were diminished or absent (the hyporesponsive state). Inoculation of naive rabbits with heat-inactivated virus was similarly ineffective; however, inoculation of this group of rabbits with viable virus 24 h later did induce full-scale acute phase responses. The possible role of cytokines in mediating the acute phase response after influenza viral challenge is discussed. Results support the hypothesis that sleep is a facet of the acute phase response involved in host defense mechanisms. PMID- 1443231 TI - Metabolic adaptation of fetal hindlimb to severe, nonlethal hypoxia. AB - To test the hypothesis that an important aspect of the fetal response to severe, nonlethal hypoxia is a relatively large reduction in oxidative metabolism and small increase in lactate production by organs whose O2 supply is selectively reduced, net fluxes of O2, glucose, pyruvate, lactate, and CO2 derived from fetal plasma lactate carbon [(CO2)PL] were measured across the hindlimb and umbilical circulations in six sheep fetuses before and at 200-260 min of hypoxia. During hypoxia, blood lactate reached a high but steady level (15.2 +/- 2.2 vs. 1.7 +/- 0.2 mM; P < 0.001). Hypoxia was induced by reducing uterine blood flow. Limb O2 uptake and (CO2)PL decreased (P < 0.01) and lactate output increased (P < 0.05) ( 83.1 +/- 13.9, -28.6 +/- 5.0, and +35.7 +/- 13.7 nmol.min-1 x g-1, respectively), while pyruvate and glucose uptakes remained similar to control. The increase in limb glycolysis was approximately 10% of the value that would compensate for the decrease in oxidative energy metabolism. The ratio of limb O2 uptake to fetus O2 uptake decreased significantly (0.247 +/- 0.029 vs. 0.447 +/- 0.036; P < 0.01). In contrast to fetal limb (CO2)PL, fetal (CO2)PL did not decrease. During severe, nonlethal hypoxia, fetal survival depends on uneven and counterbalancing organ O2 uptake and lactate metabolism. PMID- 1443232 TI - Steady-state arterial pressure-urinary output relationships during ovine pregnancy. AB - To determine the effects of long-term changes in sodium intake on mean arterial pressure (MAP) regulation during pregnancy, nonpregnant (n = 16) and 110- to 140 day pregnant (n = 13) ewes received total daily sodium intakes of 10, 30, 100, 400, and 1,200 mmol for 7 days. The sheep were housed in metabolism cages and MAP was monitored 24 h/day. Urinary sodium excretion (UNaV) followed changes in sodium intake, with steady-state levels being achieved with similar degrees of rapidity (2-3 days) in nonpregnant and pregnant sheep. At 10 mmol/day sodium intake, MAP was lower (79 +/- 1 vs. 82 +/- 2 mmHg; P < 0.01) and water intake (2,275 +/- 494 vs. 3,286 +/- 725 ml/day; P < 0.001) and 24-h urine volume (1,454 +/- 279 vs. 2,299 +/- 496 ml/day; P < 0.01) were greater in pregnant sheep. All of these variables exhibited direct relationships with increases in sodium intake. Plasma angiotensin II (pANG II) was increased in pregnancy (10.6 +/- 1.6 vs. 24.5 +/- 6.3 pg/ml; P < 0.001) at 10 mmol/day. Elevation of sodium intake suppressed pANG II to minimal levels in nonpregnant sheep, but to only 25% of the control level in pregnant sheep. During pregnancy, the renal function curve representing the steady-state MAP-UNaV relationship was shifted to lower MAP setpoint, but the sodium sensitivity of MAP was unchanged. Also, the inverse relationship of sodium intake and pANG II was blunted, suggesting a reduced role for ANG II in the maintenance of renal function during pregnancy. PMID- 1443233 TI - Sympathoadrenal-circulatory regulation of arterial pressure during orthostatic stress in young and older men. AB - Our purpose was to test the hypothesis that human aging alters sympathoadrenal circulatory control of arterial blood pressure during orthostasis. Plasma catecholamine and hemodynamic adjustments to two different forms of orthostatic stress, lower body suction (-10 to -50 mmHg) and standing, were determined in 14 young (26 +/- 1 yr) and 13 older (64 +/- 1) healthy, normally active men. During quiet supine rest, cardiac output tended to be lower and systemic vascular resistance higher in the older men, but no other differences were observed. On average, arterial blood pressure was well maintained during both forms of orthostasis in the two groups; the older men actually demonstrated better maintenance of pressure (P < 0.05) and a lesser incidence of orthostatic hypotension than the young men during lower body suction. Despite a blunted reflex tachycardia during orthostatic stress (P < 0.05), cardiac output tended to decrease less in the older men because of a smaller decline in stroke volume (P < 0.05, suction only), whereas the reflex increases in systemic vascular resistance were not different in the two groups. The whole forearm vasoconstrictor response tended to be attenuated in the older men during lower body suction, but was identical in the two groups with standing. Forearm skin vascular resistance was unaltered during lower body suction in both groups. Orthostasis-evoked increases in antecubital venous plasma norepinephrine concentrations were similar in the young and older men, whereas little or no increases in plasma epinephrine concentrations were observed in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443234 TI - Nitric oxide participates in the cerebrovasodilation elicited from cerebellar fastigial nucleus. AB - The endothelium-derived relaxing factor, probably NO, is a potent vasodilator that mediates the vasodilating action of acetylcholine (ACh). We studied whether NO participates in the cholinergic cerebrovasodilation elicited by stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized with halothane and ventilated. FN or pontine reticular formation (PRF) were stimulated through microelectrodes. Hypertension was prevented by spinal cord transection with arterial pressure maintained by intravenous phenylephrine. Cerebral blood flow (CBF) was continuously monitored through a cranial window over the sensory cortex by a laser-Doppler probe. The window was superfused with Ringer solution (pH 7.3 7.4; 37 degrees C). During Ringer superfusion FN stimulation (100 microA; 50 Hz) increased CBF by 90 +/- 7% (n = 27; P < 0.001, analysis of variance and Tukey's test) and PRF stimulation (100 microA; 100 Hz) by 128 +/- 18% (P < 0.001; n = 9). Superfusion with the guanylyl cyclase inhibitor methylene blue (MB) (1 mM) attenuated the CBF increase elicited by FN stimulation by 77 +/- 3% (n = 22; P < 0.001). MB did not affect the CBF increase elicited by PRF stimulation (+98 +/- 18%; n = 9; P > 0.05). Similarly, superfusion with the NO-synthase inhibitor nitro-L-arginine (L-NA) attenuated the CBF increase elicited by FN stimulation ( 67 +/- 3%; n = 14; P < 0.001 from Ringer) but not PRF stimulation (P > 0.05; n = 9). The CBF increases elicited by FN stimulation were not affected by the inactive isomer of nitroarginine, D-NA (P > 0.05; n = 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443235 TI - Changes in regulation of human zinc metabolism with age. AB - To assess changes in zinc metabolism with age, kinetic studies were performed in healthy adults (26 men, 21 women) aged 20-84 yr after a single oral or intravenous bolus of 65Zn. Studies covered two consecutive 9-mo periods while subjects were on a basal dietary intake of approximately 10 mg Zn/day and while taking an additional 100 mg Zn/day orally. Zinc metabolism was analyzed by compartmental analysis using data from plasma, red blood cells, urine, feces, liver, thigh, and whole body [M. E. Wastney, R. L. Aamodt, W. F. Rumble, and R. I. Henkin. Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20): R398 R408, 1986]. Changes in observed and model calculated values of zinc metabolism were assessed on age by regression. During basal state, zinc release from red blood cells decreased with age. During zinc loading, response (defined as change from basal state) of plasma zinc concentration, urinary zinc excretion, and liver zinc increased with age, while response of fraction of zinc taken up by red blood cells decreased with age. In men, response of amount of zinc absorbed increased with age and in women response of fraction of endogenous zinc excreted decreased with age. Four responses that changed with age (urinary excretion, red blood cell exchange, absorption, and endogenous excretion) occurred at previously defined sites of regulation of zinc metabolism. Results show that regulation of zinc metabolism changes with age. PMID- 1443236 TI - Systemic injection of TNF-alpha attenuates fever due to IL-1 beta and LPS in rats. AB - The effect of tumor necrosis factor-alpha (TNF-alpha) on the febrile response to interleukin-1 beta (IL-1 beta) was investigated in rats. While both of these substances are capable of causing fever when injected into rats, an earlier study showed that the injection of antiserum against TNF-alpha enhanced endotoxin [lipopolysaccharide (LPS)] fever, suggesting that physiological levels of circulating TNF may act to limit the magnitude of fever. In the present study, the intraperitoneal injection of 1 microgram/kg of TNF-alpha significantly attenuated the fever due to the intraperitoneal injection of 10 micrograms/kg of IL-1 beta. Higher doses of TNF-alpha (10 and 50 micrograms/kg injected ip) slightly lowered the febrile response to this dose of IL-1 beta, but these changes were not significant. None of these doses of TNF-alpha alone significantly altered body temperature. The injection of 1 microgram/kg of TNF alpha also significantly lowered the febrile response to the intraperitoneal injection of 10 micrograms/kg of LPS. The febrile responses to the preoptic area (POA) or intraperitoneal injection of IL-1 beta were not changed when a nonpyrogenic dose of TNF-alpha was simultaneously injected into the POA. Further studies are needed, however, before we can conclude that TNF does not act in the central nervous system to control the febrile response. These data support the hypothesis that nonpyrogenic levels of TNF act in the systemic circulation to suppress the development of fever. PMID- 1443237 TI - Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration. AB - We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L-cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats. PMID- 1443238 TI - Precocious cessation of intestinal macromolecular transport by synthetic trypsin inhibitor in suckling rats. AB - The effects of repeated oral administration of the synthetic trypsin inhibitor camostat on intestinal macromolecular transport and disaccharidase development were investigated in suckling rats. By daily treatment with camostat, bovine immunoglobulin (Ig) G transport in the intestine declined more rapidly in treated than in control rats. The absorption curve shifted to the left in treated rats 3 days before the controls. Morphological inspection of treated pups showed a decline in the number of epithelial cells that absorb bovine IgG and in their vesicle size from basal to upper regions of the villi. Maltase activity precociously increased with camostat treatment. Chronic subcutaneous injection of camostat did not cause any changes in IgG transport and maltase activity. The depression of IgG transport by oral treatment with camostat was not affected by the cholecystokinin (CCK) receptor antagonist L 364718 and was not inhibited by adrenalectomy. The absorptive responses of IgG and maltase activity were not affected by CCK-8 treatment. These data indicate that oral administration of camostat induces precocious maturation of the small intestine and that the effect is not mediated via endogenous CCK released by camostat. PMID- 1443239 TI - The listening healer in the history of psychological healing. AB - OBJECTIVE: The purpose of this paper is the assessment of the healer's listening as an aspect of the history of caring and curing, with particular attention to its place in psychological healing. METHOD: An extensive range of philosophical, religious, and medical sources from antiquity to the present were studied. RESULTS: Over the centuries, listening has been a crucial aspect of the various endeavors undertaken by healers in the interest of acquiring information from, achieving understanding of, and bringing about healing effects for sufferers. Yet it has been vision rather than hearing that has been emphasized in knowing and understanding, and looking rather than listening that has been emphasized in healing endeavors. Only around the turn of the twentieth century did there emerge the focused study of care in listening, of listening beyond the words themselves, and of the significance of the interested listener as a soothing, empathic force. CONCLUSIONS: The place of listening in depth and with empathy is a crucial element in healing. While the emphasis on looking remains significant in the gathering and appraisal of data, at times it threatens to overwhelm the need for an attentive and concerned listener. There appears to be a natural tension between the two modes that has, in modern times, been translated into a tension between the two modes that has, in modern times, been translated into a tension between a scientific mode of gaining information and a humanistic mode of knowing sufferers. A healer neglects either one at his or her peril--and at the peril of his or her patients. PMID- 1443240 TI - Problems and considerations in the valid assessment of personality disorders. AB - This article reviews evidence for the reliability and diagnostic concordance of structured-interview and self-report questionnaire methods for the diagnosis of personality disorders. The findings of nine studies that compared two or more axis II diagnostic instruments administered to the same groups of subjects are summarized. Across the eight studies with sufficient data, a summary of the overall diagnostic agreement between any two instruments yielded a low reliability (median kappa = 0.25) for making individual personality disorder diagnoses. Diagnostic concordance was lower between self-report questionnaire and interview methods than between interview methods. Comparing dimensional scores of different methods did not appreciably improve the level of agreement. The author concludes that current methods for making personality disorder diagnoses have high reliability but yield diagnoses that are not significantly comparable across methods beyond chance, which is not scientifically acceptable. Sources for the disagreement include variance due to different raters, interview occasions, data sources (self-report versus observer report), information bases obtained, and instrument sensitivity to state effects (e.g., mood). Serious problems in assessment validity may also arise from the yes/no format, which, despite probes for confirmatory examples, may fail to distinguish adequately between sporadic occurrences and longstanding patterns. Efforts should be made to improve and demonstrate the validity of axis II diagnostic methods. One route to increasing validity is to improve the clinical interview, because personality patterns are best revealed by the recurring patterns one finds when taking a systematic history. PMID- 1443241 TI - Measuring the determinants of work values for psychiatrists' services in the resource-based relative value scale study. AB - OBJECTIVE: As part of the Harvard resource-based relative value scale study, the authors investigated how well the codes in the Physician's Current Procedural Terminology, 4th edition, or CPT-4, match psychiatric services to the work involved in evaluating and managing patients and how patient care characteristics affect different levels of psychiatric work. METHOD: A random sample of over 200 psychiatrists and subspecialists was asked to use 68 typical clinical examples or vignettes to evaluate services described by CPT codes. Data were analyzed by multivariate statistical methods. RESULTS: The survey showed that the existing coding system does not adequately describe the work that psychiatrists do. Within a single code (e.g., 90844, individual medical psychotherapy), there was wide (more than twofold) variation in the estimates, from multiple measurements based on different vignettes, of the amount of work represented. Estimates of work values varied significantly according to treatment setting and patient characteristics: psychiatric services in the hospital showed an average work value 25% greater than that for office services; treating new patients involved 18% more effort than treating established patients; and treating patients described as at risk of harming self or others increased the psychiatrists' work effort by 36%. CONCLUSIONS: Revisions in coding evaluation and management services in the new Medicare fee schedule for psychiatric services should be further refined and then implemented. These revisions would bring the coding system into line with psychiatric practice, making it a better way of accounting for the relative work involved in treating patients of varying difficulty. PMID- 1443242 TI - Assessment of lineality in bipolar I linkage studies. AB - OBJECTIVE: To assess lineality in families of bipolar I probands, the authors used direct interviews of family members to reclassify families initially categorized as unilineal by family history. METHOD: The families of 1,800 treated bipolar I probands were screened by the family history method with multiple informants. If the proband had one or more affected sibs and one apparently unaffected parent, the parents (and then other available first- and second-degree relatives) were directly interviewed by psychiatrists. RESULTS: Of the 1,800 families screened, 56 were apparently suitable unilineal families with multiple affected members; 46 families were interviewed directly. After interviews with the parents, 12 families (26.1%) were found to be bilineal. Direct interviews of all available relatives in the 34 remaining families revealed that only 22 (47.8% of the 46 interviewed families) were unilineal or probably unilineal and 12 were probably bilineal. The probably bilineal families had a significantly higher proportion of siblings with unipolar disorder. In addition, the affected sibs from the probably bilineal families tended to have earlier onsets but had significantly fewer symptoms in the most severe depressive episode. CONCLUSIONS: Fewer than 50% of bipolar I families appearing unilineal according to family history were found to be unilineal by direct interviews. The phenotypic differences between the affected sibs from the probably bilineal families and those from the unilineal and probably unilineal families suggest differences in genetic mechanisms. These findings highlight the need to systematically assess lineality in all families considered for bipolar I linkage studies and support the preferential inclusion of unilineal families in linkage studies. PMID- 1443243 TI - Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study. AB - OBJECTIVE: This study investigated whether the distinction between schizoaffective disorder and affective disorders with mood-incongruent psychotic features as described in DSM-III-R is reflected by aggregation of schizophrenia in the families of probands with the former disorder and aggregation of affective disorders mainly among the relatives of probands with the latter type of disorders. METHOD: The probands were 118 inpatients with definite lifetime diagnoses of DSM-III-R schizoaffective disorder or a major mood disorder with incongruent psychotic features according to structured clinical interviews. Diagnostic information on 475 of the probands' first-degree relatives was gathered through direct interviews (with 80% of the living first-degree relatives) or the family history approach. The rates of affective and psychotic disorders among these relatives were then compared with those among the relatives of a comparison group of 109 interviewed individuals from the general population who were matched on sociodemographic factors to the inpatient probands. RESULTS: With regard to the familial aggregation of schizophrenia, the DSM-III-R distinction emerged as valid. However, the risk of unipolar affective disorders was enhanced in the families of all of the subgroups of patients studied. The unipolar/bipolar distinction in both DSM-III-R diagnostic groups was reflected by distinct patterns of bipolar disorders in the relatives. CONCLUSIONS: The results partly support the DSM-III-R dichotomy of schizoaffective disorder and affective disorders with mood-incongruent psychotic features. Although the differences between these two diagnostic groups were significant, the magnitude of the differences remained relatively modest. PMID- 1443244 TI - Reliability of best-estimate diagnosis in genetic linkage studies of major psychoses: results from the Quebec pedigree studies. AB - OBJECTIVE: Diagnostic classification and reliability are critical in genetic linkage studies of schizophrenia and bipolar disorder. To establish an optimal diagnostic procedure, the authors drew 13 methodological elements from 38 major linkage studies and workshop reports. They determined reliability for a consensus best-estimate diagnostic method based on these 13 features. METHOD: Each of 59 subjects from several large multiplex pedigrees, densely affected by either schizophrenia or bipolar disorder, received a best-estimate diagnosis from unblind diagnosticians in the field and also from a panel of four research psychiatrists who were blind to the proband's and relatives' clinical status. The best estimate was based on personal diagnostic interviews, all available medical records, and family history data. RESULTS: The diagnostic concordance between the field team and the blind psychiatric board yielded 78% to 90% agreement for the whole sample (kappa = 0.83-0.88) and 71% to 87% agreement for the subjects given field diagnoses (kappa = 0.76-0.83). The diagnoses made by the unblind field diagnosticians were biased toward a greater severity (or certainty) level in the diagnostic hierarchy (schizophrenic or bipolar) and more consistency with the most prevalent diagnosis affecting the pedigree. CONCLUSION: Since several previous linkage studies used diagnoses made by diagnosticians who were not blind to the status of the probands and the relatives or did not use a consensus best estimate diagnosis, further reliability studies of different aspects of the best estimate method and of its effect on linkage studies are needed. Such research is imperative given the serious impact of diagnostic misclassifications on genetic linkage results. PMID- 1443245 TI - Combined pharmacotherapy and psychotherapy in the acute and continuation treatment of elderly patients with recurrent major depression: a preliminary report. AB - OBJECTIVE: The authors examined the rate of response to the combination of nortriptyline and interpersonal psychotherapy for acute and continuation treatment of elderly patients with recurrent major depression. METHOD: The subjects were 73 elderly patients, 61 of whom completed treatment. Nortriptyline steady-state blood levels were maintained at 80-120 ng/ml, and interpersonal psychotherapy was administered weekly for 9.1 weeks (medium) of acute therapy and was decreased from biweekly to triweekly during 16 weeks of continuation therapy. During acute treatment nonresponding patients also received brief adjunctive pharmacotherapy with lithium or perphenazine. RESULTS: Of the 61 subjects given adequate trials of nortriptyline and interpersonal psychotherapy, 48 (78.7%) achieved full remission (Hamilton depression rating of 10 or lower over 16 weeks of continuation therapy), 10 patients (16.4%) did not respond (Hamilton rating never below 15), and three achieved only partial remission (Hamilton rating of 11 14). Early versus late onset was not associated with a difference in response rate. During the placebo-controlled, double-blind transition to maintenance therapy, 19 (76.0%) of the 25 patients randomly assigned to placebo maintenance conditions showed continued recovery and six relapsed. None of the 24 patients assigned to nortriptyline conditions relapsed. CONCLUSIONS: Use of nortriptyline plus interpersonal psychotherapy for 9.1 weeks (median) of acute and 16 weeks of continuation therapy appears to be associated with good response and relatively low attrition but about a 25% chance of relapse during double-blind discontinuation of nortriptyline. These data require confirmation in a controlled clinical trial of acute and continuation therapy. PMID- 1443246 TI - Religious coping and depression among elderly, hospitalized medically ill men. AB - OBJECTIVE: The investigators examined the frequency of religious coping among older medical inpatients, the characteristics of those who use it, and the relation between this behavior and depression. METHOD: The subjects were 850 men aged 65 years and over, without psychiatric diagnoses, who were consecutively admitted to the medical or neurological services of a southern Veterans Administration medical center. Religious coping was assessed with a three-item index. Depressive symptoms were assessed by self-rating (the Geriatric Depression Scale) and observer rating (the Hamilton Rating Scale for Depression). RESULTS: One out of every five patients reported that religious thought and/or activity was the most important strategy used to cope with illness. Variables that were associated with religious coping included black race, older age, being retired, religious affiliation, high level of social support, infrequent alcohol use, a prior history of psychiatric problems, and higher cognitive functioning. Depressive symptoms were inversely related to religious coping, an association which persisted after other sociodemographic and health correlates were controlled. When 202 men were reevaluated during their subsequent hospital admissions an average of 6 months later, religious coping was the only baseline variable that predicted lower depression scores at follow-up. CONCLUSIONS: These findings suggest that religious coping is a common behavior that is inversely related to depression in hospitalized elderly men. PMID- 1443247 TI - Visual hallucinations in patients with macular degeneration. AB - OBJECTIVE: This study was undertaken to determine the prevalence of visual hallucinations in patients with macular degeneration, describe such hallucinations phenomenologically, and possibly determine factors predisposing to their development. METHOD: Using a case-control design, the authors screened 100 consecutive patients with age-related macular degeneration for visual hallucinations. Each patient with visual hallucinations was matched to the next three patients without hallucinations. The patients and comparison subjects were compared in terms of scores on the Beck Depression Inventory, Eysenck Personality Questionnaire, Telephone Interview for Cognitive Status, and a structured questionnaire including demographic characteristics, family history, and medical and psychiatric history. Ophthalmologic data were obtained by chart review. RESULTS: Of the 100 patients, 13 experienced visual hallucinations. Four variables were significantly associated with having hallucinations: living alone, lower cognition score, history of stroke, and bilaterally worse visual acuity. Hallucinations were not associated with family or personal history of psychiatric disorder or with personality traits. In 11 (84.6%) of the 13 patients, the hallucinations had begun in association with an acute change in vision. CONCLUSION: These results indicate that visual hallucinations are prevalent among patients with macular degeneration. They appear unrelated to primary psychiatric disorder. The predisposing factors of bilaterally worse vision and living alone support an association with sensory deprivation, while history of stroke and worse cognition support a decreased cortical inhibition theory. PMID- 1443248 TI - Elderly Israeli Holocaust survivors during the Persian Gulf War: a study of psychological distress. AB - OBJECTIVE: The aim of the current study was to systematically assess the psychological effects of the Persian Gulf War on a nonclinical group of elderly Israeli civilians with and without a Holocaust background. METHOD: Sixty-one elderly Holocaust survivors and 131 elderly civilians without a Holocaust background completed questionnaires in their homes. Measures included sense of safety, symptoms of psychological distress, and levels of state and trait anxiety. RESULTS: Findings indicate that Holocaust survivors perceived higher levels of danger and reported more symptoms of acute distress than comparison subjects. In addition, they displayed higher levels of both state and trait anxiety. CONCLUSIONS: Findings do not support the notion that prior experience with extreme stress has an inoculating effect that leads to greater resilience in dealing with other forms of stress. On the contrary, Holocaust experience was found to render the elderly more vulnerable rather than less. These findings of greater vulnerability among Holocaust survivors are of particular significance since they stem from a nonclinical group. PMID- 1443249 TI - Utilization of neuropsychiatric diagnostic tests for general hospital patients with mental disorders. AB - OBJECTIVE: The author's goal was to determine the frequency and distribution of neuropsychiatric diagnostic tests provided to general hospital patients with mental disorders. METHOD: Data from the 1989 National Hospital Discharge Survey were analyzed to determine the number, proportion, and general characteristics of 11,628 discharged patients with primary diagnoses of mental disorders who underwent computerized tomography (CT) scanning of the head, EEG, and magnetic resonance imaging (MRI) of the brain. RESULTS: Of the discharged patients with mental disorders, 5.1% had received CT scans, 2.8% had received EEGs, and 0.7% had received MRI. These rates were below the rates for patients discharged with primary diagnoses of neurological disorders but above the rates for patients discharged with primary diagnoses of other medical disorders. Among the patients discharged with mental disorder diagnoses, the likelihood of receiving a CT scan or an EEG was greater if the primary diagnosis was an organic disorder or if the secondary diagnosis was a medical disorder. Patients over age 65 were also more likely to have received a CT scan. Hospital size and location had a modest influence on the likelihood of receiving a CT scan or EEG, but the ownership of the hospital and the patient's source of payment were not significant influences. CONCLUSIONS: Neuropsychiatric diagnostic testing is selectively utilized in the routine treatment of general hospital psychiatric inpatients. Clinical variables rather than institutional or financial variables appear to be the most powerful predictors of which patients are selected to receive these tests. PMID- 1443250 TI - Effect of instructional cues on schizophrenic patients' performance on the Wisconsin Card Sorting Test. AB - OBJECTIVE: Schizophrenic patients are particularly deficient on measures of executive functioning, notably the Wisconsin Card Sorting Test. This study was conducted to determine the efficacy of a cuing strategy in facilitating performance on this cognitive measure of the integrity of prefrontal brain structures and functioning. METHOD: Twenty-four schizophrenic inpatients and 24 demographically matched inpatients with mood disorders were administered the Wisconsin Card Sorting Test either with instructional cues at the beginning of the task or with the standard administration procedure. RESULTS: There was a significant benefit of cues for the patients with affective disorders as well as for the schizophrenic patients. The schizophrenic subjects in the uncued condition maintained poor but stable performance throughout the course of the task. CONCLUSIONS: The study suggests that the deficit in executive functioning of schizophrenic patients may lie in the formation of concepts, not in their application. PMID- 1443251 TI - Physical and sexual abuse histories among children with borderline personality disorder. AB - OBJECTIVE: The purpose of the study was to determine whether a history of physical or sexual abuse is more common in children with borderline personality disorder than in other children evaluated in the same outpatient psychiatric clinic. METHOD: The authors contrasted rates of abuse in 44 children diagnosed with borderline personality disorder and in 100 comparison children. RESULTS: The borderline personality disorder group had a significantly greater prevalence of physical and combined physical/sexual abuse. Sexual abuse rates alone did not differ significantly between groups. CONCLUSIONS: The finding of greater abuse in the group with borderline personality disorder supports the hypothesis that a history of trauma is associated with the disorder. PMID- 1443252 TI - Lithium-discontinuation-induced refractoriness: preliminary observations. AB - The authors used a systematic life-chart methodology to observe four patients with bipolar disorder in whom long periods (6-15 years) of effective lithium prophylaxis were followed by relapses on lithium discontinuation. Once the drug was reinstituted, it was no longer effective. The incidence, predictors, and mechanisms underlying this phenomenon all require further systematic study. The current preliminary observations suggest an additional reason for caution when lithium discontinuation in the well-maintained patient is considered. PMID- 1443253 TI - Side effects and the "blindability" of clinical drug trials. AB - A novel, simple approach to retrospective assessment of "blindability" was applied to data on outpatients in a controlled, double-blind clinical comparison of a putative antidepressant, etoperidone, and placebo. A "blind" evaluator proved capable of discriminating between the active drug and placebo on the basis of reported side effects alone, raising questions about the true blindness of the study. PMID- 1443254 TI - Fluoxetine and suicidal preoccupation. PMID- 1443255 TI - Fluoxetine in depersonalization disorder. PMID- 1443256 TI - Adverse vascular effects associated with fluoxetine. PMID- 1443257 TI - Phenelzine treatment of depression in Parkinson's disease. PMID- 1443258 TI - Antidepressants, panic disorder, and PTSD. PMID- 1443259 TI - Taking chronic fatigue syndrome seriously. PMID- 1443260 TI - Taking chronic fatigue syndrome seriously. PMID- 1443261 TI - Taking chronic fatigue syndrome seriously. PMID- 1443262 TI - Taking chronic fatigue syndrome seriously. PMID- 1443263 TI - Taking chronic fatigue syndrome seriously. PMID- 1443264 TI - Pharmacotherapy of agitation in dementia. PMID- 1443265 TI - ECT and delirium in Parkinson's disease. PMID- 1443266 TI - ECT and delirium in Parkinson's disease. PMID- 1443267 TI - ECT and delirium in Parkinson's disease. PMID- 1443268 TI - A second look at the placebo response. PMID- 1443269 TI - Sociocultural perspectives on substance abuse disorders. PMID- 1443270 TI - Cocaine abstinence: "withdrawal" or residua of chronic intoxication? PMID- 1443271 TI - Does light therapy present an ocular hazard? PMID- 1443272 TI - Patients' appearance and psychopathology. PMID- 1443273 TI - The treatment of an adult survivor of incest: a self psychological perspective. PMID- 1443274 TI - The Wolf-Man case: classical and self-psychological perspectives. AB - Freud's description of his analysis and treatment of the Wolf-Man will be forever regarded as an extraordinary clinical and theoretical achievement. What has been attempted in this paper is to demonstrate how selected aspects of the Wolf-Man case could be interpreted using a self-psychology paradigm. The intent was not to demean Freud or to undermine the theoretical and clinical contributions of drive/structure theory. Rather, I have attempted to show how Freud's analysis and treatment of the Wolf-Man might have been enhanced by a familiarity with more recent developments in psychoanalysis. PMID- 1443275 TI - Psychoanalytic reflections on language distortion and empathic listening. PMID- 1443276 TI - A Fairbairnian object-relations perspective on self-psychology. PMID- 1443277 TI - Reflections on the development of male chauvinism. PMID- 1443278 TI - Psychoanalysis and state terror in Argentina. PMID- 1443279 TI - Will the health care crisis sabotage the practice of psychotherapy? PMID- 1443280 TI - The dissolution of the dyad in psychiatry: implications for the understanding of patient-therapist sexual misconduct. AB - Psychiatry has undergone multiple changes in this century. Some twenty years ago, Kubie describe a move away from patients, particularly in those practitioners involved in academic psychiatry. His concern was warranted; such a trend appears to have involved much of psychiatry. There has been a markedly decreased emphasis in viewing the operative unit of psychiatric inquiry as a dyad of the physician and patient, in which the parties inescapably influence each other. Newer treatments tend to employ the physician as a more independent entity that applies necessary treatment to the patient. Concomitantly, we have seen a trend toward a diminishing focus on sexuality as a primary motivating force in all areas of human endeavor. Freud proposed that libidinal impulses dominated much of our behavior; later psychoanalytic theorists and founders of other modalities of treatment have focused on other sources of motivation. Within the context of a psychiatry less focused on the physician and patient in a dyadic sense, and less focused on sexuality as a universal source of motivation, we have witnessed a marked increase in interest in the sexual misconduct of psychiatrists. Comprehension of this disturbing issue in the service of prevention rests upon reversing these trends. We must attend to the dyad as a bipersonal field serving as the arena for misconduct. We must also parallel our strident disapproval of misconduct with an objective exploration of the dynamics of both parties and the human commonality of sexual feelings. This special section represents such an exploratory effort. PMID- 1443281 TI - Obstacles to the dynamic understanding of therapist-patient sexual relations. AB - Several dynamic resistances appear to interfere with rational and empirically based discourse about therapist-patient sexual misconduct. These resistances include the lure of reductionism and a longing for simplicity; wishes for "political correctness"; gender bias; and confusion about the nature of the trauma in sexual misconduct. We conclude that (1) empirical study may produce unpleasant results; (2) "politically incorrect" models of misconduct merit study with care equal to "politically correct" ones; and (3) those reenactments we call transference-countertransference should be viewed in all their human complexity. Only then will our increased understanding of misconduct offer hope of prevention. PMID- 1443282 TI - Unanswered questions about the criminalization of therapist-patient sex. AB - Even though much has been written about the issue of criminalization of therapist patient sex, many questions about the issue remain unanswered, raising doubts about the wisdom of nationwide adoption of criminalizing legislation. From a philosophical standpoint, we need to understand more fully what thoughts, emotions, and behaviors constitute consent. Furthermore we must determine how much value to give consent in relation to other social values and goals. From a clinical standpoint we still need a better understanding of what constitutes the therapist-patient relationship: what it is and when it is over. We must also examine more carefully the nature of power within a psychotherapeutic relationship. From a legal standpoint we must determine how criminalization affects constitutional privacy rights, as embodied both in state constitutions and the federal Constitution. From an empirical standpoint we need to assess the efficacy of current criminalization statutes and determine their effect on tort compensation for patient victims. We also need to assess the practical application of these statutes by juries. Without more thorough analysis of all the issues raised, the criminalization of patient-therapist sex by state legislatures may in fact cause more harm than good. PMID- 1443283 TI - Risk management in the practice of behavior therapy: boundaries and behavior. AB - Behavior therapy represents a treatment modality widely utilized by clinicians but to date insufficiently examined from the risk-management standpoint. Given that the determination of negligence is dependent on the role of the therapist as proximate cause of the adverse outcome and on the availability of an accepted standard of care from which deviations can be specified, a number of general characteristics of behavior therapy may render its practitioners potentially vulnerable to litigation. These may include its directiveness, its replicability, and its methodologic rigor. Similarly, certain specific behavioral techniques may carry some medicolegal risks, including the use of aversion methods, utilization of family members or other lay cotherapists, response cost, and exposure therapies. In addition, therapeutic boundaries in behavioral treatment may be different from those in psychoanalytic therapy, allowing for therapist practices that might otherwise be considered unusual or in themselves negligent, but the therapist may have a heavier burden of justification in such cases. The authors suggest that recognition of the possibility of adverse results, ongoing and competent informed consent, adequate documentation, willingness to consult, and careful monitoring of treatment outcome may help mitigate the medicolegal risks of these procedures. PMID- 1443284 TI - The prevention of psychotherapist sexual misconduct: avoiding the slippery slope. AB - Therapist sexual misconduct has its genesis in the therapeutic relationship. The mental health professions have long recognized the delicacy with which the therapist must handle the therapeutic relationship, with its power imbalance, inherent vulnerability of the patient, and transference and countertransference reactions. The prevention of sexual contact starts with the careful attention to boundary violations, which, though themselves perhaps not harmful, may escalate into sexualized behavior. Methods of preventing this behavior include the establishment of clear guidelines for practitioners and the expansion of the educational process for therapists, therapists' employers, patients, and other professionals. Last resorts lie in the legal and quasi-legal proceedings available to victims, such as civil suits for damages, criminal complaints, board of licensing complaints, and actions before professional associations. The best method of preventing sexual contact with patients involves respecting the boundaries of the professional relationship and avoidance of the slippery slope. PMID- 1443285 TI - False sexual-abuse allegations by children and adolescents: contextual factors and clinical subtypes. AB - The authors review the empirical literature concerning the frequency of false allegations of sexual abuse as well as the case report literature that describes individual episodes of false allegations in detail. The authors then construct a clinical typology that is derived from the literature and their own clinical experience with similar cases. The specific subtypes of the typology are: (1) False allegation in the context of a custody dispute, (2) false allegations resulting from psychological disturbance on the part of the accuser, (3) false allegation as a conscious manipulation by the child or adolescent and, (4) false allegations based on iatrogenic factors. Clinical examples of each subtype are presented. The case material presented and reviewed indicates the importance of attending to the contextual factors surrounding the allegation and pursuing a detailed comprehensive evaluation that is as free of bias as possible. PMID- 1443286 TI - Professionals' attitudes towards sex between institutionalized patients. AB - Sexual activity among institutionalized patients has always been an issue of concern to institutions. Despite this fact, there has been little consensus about how patient sexuality should be dealt with. Nor have clinical insights with respect to patient sexuality been empirically tested. Given the diversity of beliefs and policies in this area, guidelines concerning sexual activity among hospitalized mental patients seem to be badly needed. We examined the following six factors that we thought might influence staff decisions: (1) the competence of a patient to engage in sexual activity, (2) the degree of consent, (3) the nature of sexual activity (e.g., hugging vs. genital relations), (4) the location of sexual activity (e.g., in bedroom vs. on grounds), (5) the sex of the initiating patient (6) the sex of the other patients. We hypothesized that mental health professionals, both as members of the community at large and as professionals, would have conventional moral views (as defined by Kohlberg) towards sexual activity. Supporting this hypothesis, of the six factors listed above, only location of the sexual activity and form of the sexual activity affected judgements on sexual activity significantly. The professionals interviewed appeared to be most condemning of homosexual acts, and least condemning of hugging. Although we had hypothesized that profession norms of consent and competence would be significant factors, they were not. The core implication of our study is that mental health professionals need training on competence assessment and its use in decision making and must reexamine their own prejudices (e.g., homophobia) to clarify their decision making about institutional policies. PMID- 1443287 TI - Dynamics for communications data. AB - To create a complex dynamical model for a complex system, it is normally necessary to have a directed graph of the network, a dynamical model for each node, and a coupling function for each directed edge. But in many applications, the only observable data consists of communications from one node to another. In this situation, the modeler may infer a complex dynamical model for the network without any explicit knowledge of the independent dynamical behavior of the component systems (nodes). Here we present one procedure for this type of modeling problem, inspired by the attractor reconstruction procedure of chaos theory. Part of this proposal consists of a strategy for computer graphic presentation of the interactive dynamics of the complex system (or social network of dynamical schemes) called a netscope. We can imagine applications to diverse situations, such as decision groups, management, forecasting, international relations, classroom monitoring, therapy (personal, family, group, etc.) and distributed processors, to name a few. PMID- 1443288 TI - On deciphering the book of nature: human communication in psychotherapy. AB - The tools of contemporary applied mathematics reveal important hidden regularities amidst the ongoing interactive feedback phenomena occurring in interactional or dynamical systems in nature where everything affects everything else. Badalamenti and Langs investigate each therapy session as a continuous sequential emergence of interrelated communicative events (or communicative states) which meet the criteria of a dynamical system. Applying mathematical modeling the authors demonstrate how otherwise hidden regularities occurring between patients and therapists become accessible to us that are unavailable to our unaided powers of observation, intuition, and thought. This is a systems or population investigation of clinical interaction that begins in a qualitative or domain mode, but which opens immediately toward statistical and formal modes of discussion. It can lead to statements of properties and laws that meet the criteria of scientific dialogue and validity. It provides the clinician with guidelines for making interpretations and for assessing their immediate subsequent effect. It is distinguished from the essentialist approach at the foundation of traditional clinical thought which provides no access to such feedback phenomena and their properties. Communicative Psychoanalysts have adopted the systems perspective and are evolving a clinical language and treatment based upon its principles and discoveries. PMID- 1443289 TI - Clinical consequences of a formal mode of science of psychoanalysis and psychotherapy. AB - The paper has presented some ways in which existing formal-mode science results are of importance to the practicing clinician. Stress was placed on the quantification and mathematical identification of countertransference difficulties. Formal science results allow for deep insight into the effects of various approaches to doing psychotherapy that have not been previously available. By adding a new dimension to psychoanalytic observation and understanding, formal science studies of the deeper nature of the human mind and of the therapeutic interaction should help in time to lead to major revisions in clinical theory and practice. PMID- 1443290 TI - Psychotherapy with the neuropsychologically impaired adult. AB - Despite opinions to the contrary, psychotherapy can be conducted with probably all but severely brain-impaired patients, albeit with some modification. The challenge is for the clinician to tailor his/her training to meet the needs of brain-impaired patients. There are certain real limitations, however, of neuropsychologically impaired patients that make psychotherapeutic attempts difficult. Assessment of patients' awareness of their losses, and of the implications of these losses is basic to an understanding of the emotional reactions observed. Screening and/or evaluation of certain neuropsychological functions is vital, as these functions have direct impact upon treatment efficacy. Traditionally, brain impairment has been thought to exacerbate premorbid or underlying character traits. An explanation is proposed for this traditional view of "exacerbation of premorbid style," in terms of decreased problem-solving skills, greater rigidity, and inherent increased strain of brain impairment. Neuropsychological deficits may interact with premorbid character types to produce some (predictable) behavioral alterations. Adjustments are required to accommodate to the deficits of brain-impaired patients, while retaining the richness of subjective experience in the clinical interaction. In treating neuropsychologically impaired persons, a model of equilibrium is thus suggested to balance patients' deficits with the therapist's interactions. PMID- 1443291 TI - Working through conflict with self-destructive preschool children. AB - This case history charts the treatment of a preschooler who first presented at the age of three years and ten months with aggressive and self-destructive behaviors. During the initial months of treatment, the therapist focused upon establishing a therapeutic alliance with the child in order to evoke a transference reaction. Compelling evidence of the transference in this case occurred in the ninth month of treatment when the therapist told the child that she would be going on vacation. The child, whose own mother had abandoned him several times, responded with uncharacteristic physical and verbal abuse. Although the child engaged in aggressive and self-destructive play enactments almost from the onset of treatment, these behaviors intensified from the fifth month of treatment onwards, as it became evident that he had entered the working through phase. Aggressive impulses were shown in his manipulation of toys and other objects, and self-destructive episodes emerged in the child's incessant efforts to jump from chairs and tables, as well as in repeated threats to "shoot" himself with a toy gun. The therapist was sensitive to the child's need to continually repeat and gradually modify these behaviors. She permitted their display without exhibiting shock or alarm, but at the same time, expressed concern for the child's safety and reinforced this concern by setting limits on his unacceptable behavior. Gradually, the child's self-destructive and aggressive tendencies abated. Further evidence that the conflict had been worked through was also seen in the child's ability to express a more realistic assessment of his home environment, one which reconciled the conflict between "good" and "bad" impulses. This advancement in perception was demonstrated by the child's verbal recognition that while his mother was capable of doing "bad" things, she was still his mother and he loved her. Prior to the termination of treatment, both the child's grandmother and teachers reported significant improvement in the child's behavior and linguistic abilities. PMID- 1443292 TI - Trends in sexual behavior and the HIV pandemic. PMID- 1443293 TI - Perspectives on HIV/AIDS epidemiology and prevention from the Eighth International Conference on AIDS. AB - The Eighth International AIDS Symposium in Amsterdam, the Netherlands, provided updated scientific and programmatic information on the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) to thousands of interested participants. As in the other scientific areas, the amount of information presented in epidemiology and prevention was overwhelming; however, the scientific progress described was steady but incremental. This commentary summarizes progress made in three selected areas that were highlighted during the meeting's scientific session and a fourth that received widespread media attention: (1) the epidemiology of HIV/AIDS in heterosexual women; (2) tuberculosis as an increasing opportunistic pathogen in HIV-infected persons; (3) prevention research, practice, and policy; and (4) preliminary reports of severe immunodeficiency in persons without evident HIV infection. In order to stem HIV transmission worldwide, a safe and effective vaccine is urgently needed. Currently, in the absence of such a vaccine, it is crucial for all of the world's communities to apply the best science-based prevention methods available. PMID- 1443294 TI - The double bind in science policy and the protection of women from HIV infection. PMID- 1443295 TI - Commentary: methods women can use that may prevent sexually transmitted disease, including HIV. AB - Although sexually transmitted diseases, including human immunodeficiency virus (HIV), are a major concern for women, few prevention messages are targeted specifically to women. Those that are generally stress abstaining, altering the number or selection of partners, and urging partners to use condoms. But these behaviors may be unrealistic for many women, particularly women who are at highest risk for sexually transmitted diseases, because they require significant changes in life-style or depend on male-controlled condom use. Recommendation of contraceptives for prevention of sexually transmitted diseases depends largely on how well specific methods perform under controlled conditions, either in the laboratory or in clinical trials. Observational studies, which better reflect day to-day use, indicate that condoms, barriers, and spermicides, used properly and consistently, can provide substantial protection against various sexually transmitted diseases. Condoms can similarly help protect against HIV, but studies of barriers and spermicides are scant and currently inconclusive. Finally, those methods that are controlled by women are consistently more effective in preventing sexually transmitted diseases. Thus, although condoms used well are still the best choice, the imperative for female-controlled methods indicates that diaphragms and spermicides should receive greater emphasis in prevention messages. PMID- 1443296 TI - Commentary: the quest for women's prophylactic methods--hopes vs science. AB - The companion article by Rosenberg and Gollub in this issue summarizes data from 10 observational studies and concludes that female-controlled contraceptive methods, under typical conditions, are comparable to condoms in preventing sexually transmitted diseases and should be merchandized as such. While we agree that chemical and mechanical contraceptives provide protection against some sexually transmitted diseases, we think the authors have overstated the scientific case for these methods, especially in comparison with the condom. We think the current data remain inconclusive regarding the absolute protection of spermicides against the human immunodeficiency virus and their level of protection--relative to that of the condom--against other sexually transmitted diseases. Three reasons account for our differences: the limitations in the comparative data; the reported adverse effects of spermicides on vaginal conditions, including genital ulcers; and the relative value of condoms, even under typical conditions, in preventing sexually transmitted diseases. For these reasons, we would currently counsel both women and men who practice high-risk sexual behaviors to use condoms as their first line of defense. If this is unacceptable, the female barriers become a fallback position to protect against bacterial sexually transmitted diseases. PMID- 1443297 TI - Community AIDS/HIV risk reduction: the effects of endorsements by popular people in three cities. AB - OBJECTIVES: It is critical to extend community-level acquired immunodeficiency syndrome (AIDS) prevention efforts beyond education alone and to develop models that better encourage behavioral changes. Gay men in small cities are vulnerable to human immunodeficiency virus (HIV) infection due to continued high rates of risk behavior. This research introduced an intervention that trained popular people to serve as behavioral change endorsers to peers sequentially across three different cities. METHODS: Populationwide surveys were conducted of all men patronizing gay clubs in each city to establish risk behavior base rates. After a small cadre of popular "trendsetters" were identified, they received training in approaches for peer education and then contracted to communicate risk reduction recommendations and endorsements to friends. Surveys were repeated at regular intervals in all cities, with the same intervention introduced in lagged fashion across each community. RESULTS: Intervention consistently produced systematic reductions in the population's high-risk behavior (unprotected anal intercourse) of 15% to 29% from baseline levels, with the same pattern of effects sequentially replicated in all three cities. CONCLUSIONS: This constitutes the first controlled, multiple-city test of an HIV prevention model targeting communities. The results support the utility of norm-changing approaches to reduce HIV risk behavior. PMID- 1443298 TI - High-risk sexual behavior and condom use among gay and bisexual African-American men. AB - OBJECTIVES: Little is known about the human immunodeficiency virus (HIV) high risk sexual practices of gay and bisexual African-American men. These data are needed so that better interventions can be developed and implemented in this population. METHODS: The frequency and correlates of unprotected anal intercourse were examined among 250 gay and bisexual African-American men in the San Francisco Bay Area. The cohort was recruited in 1990 from bars, bathhouses, and erotic bookstores, and through African-American gay organizations, street outreach, advertisements in gay mainstream and African-American newspapers, health clinics, and personal referral from other participants. RESULTS: More than 50% of the men in our sample reported having unprotected anal intercourse in the past 6 months, a considerably higher percentage than that among gay White men in San Francisco through 1988 and 1989. Men who practiced unprotected anal intercourse were more likely to be poor, to have been paid for sex, or to have used injection drugs; to have a higher perceived risk of HIV infection; and to report less social support for concerns about risky sexual behavior. Condom norms, condom efficacy, and negative expectations about using condoms predicted these men's failure to use them. CONCLUSION: In the second decade of the acquired immunodeficiency syndrome epidemic, risk reduction programs are still needed for gay and bisexual African-American men. PMID- 1443299 TI - The completeness of AIDS case reporting, 1988: a multisite collaborative surveillance project. AB - OBJECTIVES: The purpose of this study was to evaluate the completeness of acquired immunodeficiency syndrome (AIDS) case reporting. METHODS: Statewide or hospital-specific 1988 medical records were linked with AIDS surveillance in six sites. Medical records were reviewed for persons who had diagnoses suggesting human immunodeficiency virus (HIV) infection or AIDS but were not reported to AIDS surveillance by September 1989. RESULTS: Among 4500 hospitalized persons diagnosed with AIDS through 1988 in the six sites, completeness of reporting was 92% (95% CI = 89%, 96%; range across sites = 89% to 97%). Completeness of reporting was high in males (92%), females (95%), Whites (95%), Blacks (90%), Hispanics (92%), men reporting sexual contact with men (92%), persons reporting injecting-drug use (91%), and persons exposed to HIV through heterosexual contact (99%). In Medicaid enrollees (two states), completeness of reporting was 99% (95% CI = 95%, 99%) in inpatients and 90% (95% CI = 79%, 90%) in outpatients. Of previously reported persons with AIDS, 82% were reported within 5 months of diagnosis. CONCLUSIONS: Completeness of AIDS reporting was high, overall and in each major demographic and HIV exposure group. These results demonstrate that current surveillance data in these six sites provide timely and accurate information regarding persons with AIDS. PMID- 1443300 TI - The reporting of HIV/AIDS deaths in women. AB - OBJECTIVE: This study was undertaken to assess the completeness of vital statistics and case reports of acquired immunodeficiency syndrome (AIDS) in measuring human immunodeficiency virus (HIV)-related mortality in women 15 through 44 years of age. METHODS: We used vital records to determine the number of deaths attributed to HIV infection and excess deaths due to causes that have increased in tandem with the HIV epidemic. RESULTS: In 1988, among women 15 through 44 years of age, there were 1365 deaths with HIV infection listed as the underlying cause, 202 deaths with HIV infection listed as an associated cause, and 149 excess deaths due to conditions highly associated with HIV infection (subtotal = 1716). In addition, there were 780 excess deaths due to causes that may be related to HIV infection or illicit drug use (maximum estimate of HIV related deaths = 2496). Of the deaths that occurred in 1988, 1532 were reported through AIDS surveillance (1668 deaths when adjusted for reporting delays). CONCLUSIONS: Underlying-cause-of-death vital records and AIDS surveillance identified 55% to 80% and 67% to 97%, respectively, of HIV-related deaths in women 15 through 44 years of age in 1988. The wide ranges of these estimates reflect the potential role of both HIV infection and drug use in contributing to excess mortality. PMID- 1443301 TI - Responses to anonymous questionnaires concerning sexual behavior: a method to examine potential biases. AB - OBJECTIVES: Low response rates to voluntary surveys raise questions about how representative the responses are. We compared the behavior and attitudes of responders, willing and reluctant, and nonresponders to anonymous questionnaires about behaviors that might expose participants to the human immunodeficiency virus (HIV). METHODS: Questionnaires were sent to 1080 Danish adults 18 through 59 years including explicit questions about sexual acts and illegal drug use. Identical questionnaires were sent to 3600 other Danes, similarly chosen; packets sent to these persons included cards to be returned separately informing us that they had responded. Questionnaires were sent twice more to nonresponders, who, if they then responded, were considered reluctant responders. One hundred nonresponders were telephoned and asked why they had refused to respond. RESULTS: Enclosing return cards did not affect initial response rate, but prompting boosted replies from 52% to 73%. However, behaviors were generally similar among initial and reluctant responders. One third of nonresponders agreed to respond if we wished (total potential response: 82%). In general, the reasons for nonresponse did not suggest that the life-styles of nonresponders placed them at risk for HIV infection. CONCLUSIONS: This method provides a simple, inexpensive approach to improving response rates and learning about the biases of reluctant responders and nonresponders. PMID- 1443302 TI - Pneumococcal bacteremia in Monroe County, New York. AB - OBJECTIVES: Knowledge of the epidemiology of pneumococcal disease is critical for public health planning, evaluation of preventive strategies, and development of immunization recommendations. METHODS: We studied the incidence and case-fatality rates of pneumococcal bacteremia as a proxy for pneumococcal disease in Monroe County, New York, from 1985 through 1989 by reviewing the laboratory and clinical care records of all cases occurring among residents. RESULTS: There were 671 cases identified, for an overall yearly rate of 18.8 per 100,000. The rates were highest in the very young, in the very old, and in non-White populations. Age specific rates were consistently higher in Blacks than in Whites. Predisposing medical conditions were present in 61% of cases. Case-fatality rates were 15% overall, 27% in those with predisposing medical conditions, and approximately 30% in Blacks older than 55 years and Whites older than 65 years. CONCLUSIONS: This study documents the incidence of and mortality from pneumococcal bacteremia. It supports previous observations that Black populations have an increased risk of invasive pneumococcal infection and suggests that immunization should be considered for Blacks older than 55 years. PMID- 1443303 TI - Disability in occupations in a national sample. AB - OBJECTIVES: We sought to develop lists of jobs whose members reported high and low levels of functional disability. METHODS: Samples of women (n = 6096) and men (n = 3653) were drawn from the National Health and Nutrition Examination Survey I Epidemiological Follow-up. Disability was measured with a modified Stanford Health Assessment Questionnaire. We analyzed women and men separately, and we calculated average disability indices within longest-held occupations while adjusting for age, age-squared, married spouse present, and education. We minimized attrition bias with an econometric technique. RESULTS: From highest to lowest association with disability, the female broad occupations ranking was as follows: farming, no occupation, laborers, service, technicians, operatives, crafts workers, transportation operators, professionals, sales workers, administrative support, and managers. The male broad occupations ranking was as follows: no occupation, farming, operatives, crafts workers, service, technicians, manager, administrative support, sales, and professionals. The highest levels of disability for women and men occurred among nonconstruction laborers, farm workers, twisting machine operators, servants, machinery maintenance workers, mining machine operators, and bus drivers. CONCLUSIONS: Our results suggest that, in understanding levels of functional disability, occupational safety and health play a larger role than is generally assumed. PMID- 1443304 TI - Passive smoking and lung cancer in nonsmoking women. AB - OBJECTIVES: The causes of lung cancer among nonsmokers are not clearly understood. To further evaluate the relation between passive smoke exposure and lung cancer in nonsmoking women, we conducted a population-based, case-control study. METHODS: Case patients (n = 618), identified through the Missouri Cancer Registry for the period 1986 through 1991, included 432 lifetime nonsmokers and 186 ex-smokers who had stopped at least 15 years before diagnosis or who had smoked for less than 1 pack-year. Control subjects (n = 1402) were selected from driver's license and Medicare files. RESULTS: No increased risk of lung cancer was associated with childhood passive smoke exposure. Adulthood analyses showed an increased lung cancer risk for lifetime nonsmokers with exposure of more than 40 pack-years from all household members (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0, 1.8) or from spouses only (OR = 1.3; 95% CI = 1.0, 1.7). When the time-weighted product of pack-years and average hours exposed per day was considered, a 30% excess risk was shown at the highest quartile of exposure among lifetime nonsmokers. CONCLUSIONS: Ours and other recent studies suggest a small but consistent increased risk of lung cancer from passive smoking. Comprehensive actions to limit smoking in public places and worksites are well advised. PMID- 1443305 TI - HIV antibody testing and posttest counseling in the United States: data from the 1989 National Health Interview Survey. AB - To see how successful human immunodeficiency virus (HIV) counseling and testing efforts have been in testing the United States population, particularly among those at increased risk for HIV infection, we analyzed data from the 1989 National Health Interview Survey. Twenty percent of the NHIS sample (or, in terms of the general US population, an estimated 36 million persons) reported having been tested for HIV antibodies, mostly through blood donations. Although persons with increased risk of HIV infection had been tested and counseled at a much higher rate than the general population, the majority of this group had not yet been tested. PMID- 1443306 TI - Decontamination of an HIV-contaminated CPR manikin. AB - There has been a concern that the number of persons engaging in cardiopulmonary resuscitation (CPR) training could decline because of questions about human immunodeficiency virus (HIV-1) transmission. We investigated the theoretical possibility that a CPR manikin might serve as a fomite for HIV-1 transmission. Decontamination protocols were tested by using elevated levels of virus and decreasing decontamination times. Even under these compromising conditions, however, decontamination was effective. PMID- 1443307 TI - Trends in prevalences of behavioral risk factors: recent Hawaiian experience. AB - Recent time trends were studied for the prevalences of behavioral risk factors in Hawaii during the 5-year period from 1986 through 1990. The presence of linear time trend was analyzed by the multiple logistic regression method on weighted data, adjusting for confounding factors. The risk factors studied were seatbelt nonuse, lack of exercise, obesity, hypertension, smoking, acute drinking, chronic drinking, and driving while intoxicated. Seatbelt nonuse showed a significant decline, from 8.6% to 4.8%, with a mean annual decrease of 0.9 percentage point. Lack of exercise and obesity increased steadily, from 48.0% to 62.4% and from 16.7% to 21.6%, respectively, with respective annual mean increases of 3.3 and 1.4 percentage points. PMID- 1443308 TI - Predictors of shelter use among low-income families: psychiatric history, substance abuse, and victimization. AB - For poor housed and homeless families in New York City, NY, we examined the degree to which psychiatric and substance-abuse problems and victimization placed the families at elevated risk of requiring emergency housing, and we documented the prevalence of such problems. These problems were infrequently reported by both groups. However, past mental hospitalization, treatment in a detoxification center, childhood sexual abuse, and adult physical abuse were associated with increased risk of homelessness. PMID- 1443309 TI - Cumulative trauma disorders of the hand and wrist in the auto industry. AB - Surveillance for cumulative trauma disorders (CTDs) of the hand and wrist was carried out in five US automotive plants from 1985 to 1986, using Occupational Safety and Health Administration (OSHA) Form 200 injury and illness logs and medical insurance claims. Results using both record sources indicated that hand and wrist disorders may be more common in foundries than in other types of automotive plants. Similarly, in assembly plants, employees in certain departments appeared to be at higher risk for CTDs. Although our results are based on small numbers of cases, they suggest plants and departments that might be targeted for more detailed investigation. PMID- 1443310 TI - A quality-of-life method for estimating the value of avoided morbidity. AB - We developed a quality-of-life method for valuing changes in health status. Our model determines changes in health attributes for different illnesses and then estimates the dollar value of the corresponding welfare losses. We used our quality-of-life approach to estimate willingness to pay to avoid asthma, a headache, a cough, bronchitis, and arthritis. Estimates derived using our method are similar to those obtained from more expensive and restrictive traditional methods. PMID- 1443311 TI - The Supreme Court, abortion, and the jurisprudence of class. AB - The US Supreme Court's decision in Planned Parenthood of Southeastern Pennsylvania v Casey both protects a woman's liberty to choose to terminate her pregnancy and permits the state to make it more difficult for her to exercise her choice. In their opinion on the case, Justices O'Connor, Kennedy, and Souter eloquently defend constitutional protection of the right to make intimate decisions like continuing or ending a pregnancy. At the same time, they permit the state to try to persuade pregnant women not to have abortions and to make abortion harder to obtain and more costly, as long as the state's methods do not create an "undue burden" on the decision. Any restriction on abortion is a burden; whether it is "undue" (and therefore unconstitutional) depends on one's circumstances. The Court appears to view the difference between an undue burden and mere inconvenience from the perspective of privilege. The restrictions that were upheld may not significantly affect middle-class access to abortion, but they could prove insurmountable for many less privileged women. PMID- 1443312 TI - The validity of self-reported condom use. PMID- 1443313 TI - Community health and odor pollution regulation. PMID- 1443314 TI - Arthroscopic treatment of sports-related synovitis of the ankle. AB - We describe nine cases of sports-related synovitis of the ankle joint with a followup of 24 to 44 months (average, 30.9). It affects young athletes and occurs after episodes of acute or recurrent inversion ankle sprains or undisplaced ankle fractures. The patients complain of morning pain and stiffness along with increased pain and swelling with attempted athletic participation. All ankles were stable and all failed to respond to at least 6 months of conservative treatment. The technetium bone scans were positive in eight of the cases. During arthroscopy, a hypertrophic anterior-chamber synovitis was found and treated by arthroscopic partial synovectomy. The results were excellent in eight of the patients in whom symptoms resolved, allowing full return to their previous sports, and fair in one case. The only complication was one superficial wound infection. PMID- 1443315 TI - Loss of motion after anterior cruciate ligament reconstruction. AB - We did a retrospective review and follow-up examination to investigate the incidence, risk factors, and outcome of patients who developed loss of motion after arthroscopic anterior cruciate ligament reconstruction. Two hundred forty four patients with a minimum followup of 1 year were reviewed. Loss of motion (defined as a loss of extension of more than 10 degrees or flexion of less than 125 degrees) was identified in 27 patients for an overall incidence of 11.1%. Factors associated with loss of motion included acute reconstruction (less than 1 month from initial injury), male sex, and concomitant medial collateral ligament repair or posterior oblique ligament reefing or both. Twenty-one patients required surgery to regain their motion; three patients required a second procedure. Twenty-one of 27 patients with loss of motion underwent a detailed followup and were compared with 24 randomly chosen controls who had a normal range of motion after anterior cruciate ligament reconstruction. At followup, patients who experienced loss of motion had a significant decrease in noninvolved to involved knee extension and flexion compared to the control patients. There was no difference between our patients and the controls regarding patellofemoral problems, anterior knee laxity, and functional strength. Sixty-seven percent of patients with loss of motion had a good or excellent result in comparison to 80% of the controls. PMID- 1443316 TI - Anterior cruciate ligament reconstruction using a composite collagenous prosthesis. A biomechanical and histologic study in rabbits. AB - We evaluated a prototype composite collagenous anterior cruciate ligament replacement device designed to possess the advantages of biological grafts and synthetic materials. Collagenous anterior cruciate ligament prostheses were made by embedding 225 reconstituted type I collagen fibers in a type I collagen matrix, and placing polymethylmethacrylate bone fixation plugs on the ends. The collagenous prosthesis was used to replace the anterior cruciate ligament of 31 mature rabbits. At 4 and 20 weeks postimplantation, histologic and mechanical studies were performed on the developing neoligament tissue, and compared to values for the contralateral sham-operated control. At 4 weeks, neoligament tissue infiltrated the collagen fibers of the prostheses. The tibial bone tunnel attachment site contained new bone approaching the fibrous neoligament. The glutaraldehyde-treated prosthetic fibers appeared intact, while the carbodiimide treated prosthetic fibers began to resorb. The ultimate load and ultimate tensile strength of femur-neoligament-tibia complexes had decreased. At 20 weeks, glutaraldehyde-treated fibers appeared partially intact; in contrast, the carbodiimide-treated prostheses appeared to be completely degraded, and were replaced by organized, crimped neoligament tissue. The ultimate tensile strength and ultimate load increased substantially due to deposition and remodeling of neoligament tissue. The neoligament ultimate load was 2 to 4 times the initial load value of the prosthesis. Implantation of a resorbable, composite collagenous anterior cruciate ligament prosthesis encourages the development of functional neoligament tissue. Studies are underway to optimize the mechanical and biological properties of the prostheses. PMID- 1443317 TI - Cryotherapy-induced nerve injury. AB - Cryotherapy is a frequently used therapeutic modality in the treatment of athletic injuries. Peripheral nerve injury can result from the use of cryotherapy and cause temporary disability for the athlete. Six cases of peripheral nerve injury are reviewed. All cases resolved spontaneously. To avoid this complication, one should consider the location of major peripheral nerves, the thickness of the overlying subcutaneous fat, and the duration of tissue cooling. PMID- 1443318 TI - Extensor mechanism function after patellar tendon graft harvest for anterior cruciate ligament reconstruction. AB - We evaluated extensor mechanism function in 10 patients after they had arthroscopically assisted ACL reconstruction using the central third of the patellar tendon. The patients were randomly selected 12 to 24 months after reconstruction. All had rehabilitation where range of motion was initiated within the 1st postoperative week. All patients stated that they were satisfied and considered their knee to be stable. The KT-1000 maximum measurements (30 to 40 pounds) averaged an increase of 1.7 mm when compared with the opposite knee. Subjective complaints, such as anterior knee pain, grating, and weakness, were common and only 3 of 10 patients returned to all of their preinjury sports. Persistent radiographic abnormalities were common. Physical examination and functional testing also revealed persistent dysfunction of the extensor mechanism in patients with radiographic abnormalities. Isokinetic testing at 60 deg/sec showed an average quadriceps deficit of 18% compared to the normal extremity. Axial computed tomography scans revealed significant decrease in quadriceps cross sectional area. Magnetic resonance imaging and computed tomography confirmed persistent defects at the harvest site; there was significant anterior knee scar formation in these patients. Despite achieving ligamentous stability, patients still experienced permanent weakness, functional deficits, patellar chondrosis, and pain after ACL reconstruction using the central one-third of the patellar tendon. PMID- 1443319 TI - Quadriceps femoris muscle activity in patellofemoral pain syndrome. AB - To elucidate and attempt to dissociate the two mechanisms, neuromuscular and mechanical, underlying patellofemoral pain syndrome, 18 subjects, divided into two groups based on a diagnosis of patellofemoral pain syndrome and the knee Q angle, were studied. The control group was asymptomatic and exhibited a normal Q angle (mean, 8.25 degrees), whereas the other group, diagnosed as patellofemoral pain syndrome patients, reported knee pain and had an above-normal Q angle (mean, 21.05 degrees). All subjects were tested for isometric maximum knee extension at 90 degrees, 30 degrees, and 15 degrees of knee flexion while they were seated in a special restraining chair. During testing, surface electromyography at the oblique and long fibers of the vastus medialis, and at the vastus lateralis were recorded along with the knee moment of force. The integrated electromyographic signals associated with the peak torque for all of the vastus muscles, along with the vastus medialis obliquus:vastus lateralis and vastus medialis longus:vastus lateralis activity ratios showed no significant differences between groups nor between the three angles, suggesting that all vasti measured were consistently active throughout the studied range of motion. This suggests that the neural drive was not affected in the patellofemoral pain syndrome patients. However, when the five patients showing the largest Q angles were isolated, they revealed a significantly smaller vastus medialis obliquus:vastus lateralis ratio when compared to the other group. The same ratio was also significantly smaller at 15 degrees compared to 90 degrees.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443320 TI - Os trigonum impingement in dancers. AB - Sixteen patients underwent surgical excision of an impinging ossicle through a posterior lateral approach. Twelve of these patients (15 ankles) were available for followup and were retrospectively surveyed at an average of 28 months after surgery. There were 9 women and 3 men. Nine were professional ballet dancers and 3 were students of advanced ballet schools. Preoperative symptoms included pain localized to the posterior ankle, limitation of motion, weakness, swelling, or neurologic changes associated with dance activities. All patients were severely hampered in their dance participation and had failed nonsurgical therapies. Postoperatively, all patients followed an aggressive rehabilitation protocol. All had improvement in their impingement symptoms; eight (67%) still had occasional discomfort. All professional dancers returned to unrestricted dance activity. The mean time to full activity was 3 months. One patient had a superficial wound infection requiring antibiotic treatment and another suffered a transient tibial nerve neurapraxia. Both of these complications resolved without sequelae. We conclude that posterior ankle impingement in ballet dancers, caused by an os trigonum and resistant to nonsurgical therapies, is effectively treated with simple excision of the offending structure. PMID- 1443321 TI - Meniscal repair using fibrin sealant and endothelial cell growth factor. An experimental study in dogs. AB - The effect of fibrin sealant and endothelial cell growth factor on the healing of defects of the avascular portion of canine menisci was investigated in 30 menisci of 15 adult mongrel dogs. The defects were treated in one of three ways: Group 1, the defect was left empty; Group 2, the defect was filled with fibrin sealant; and Group 3, the defect was filled with fibrin sealant and endothelial cell growth factor. The healing process was evaluated macroscopically and histologically at intervals of 1, 2, 6, 12, and 24 weeks. The average percentage of each defect that was filled with connective tissue was 5% in Group 1, 76.6% in Group 2, and 89.4% in Group 3. In the early phase of this repair, the extrinsic pannus-like tissue that contained many capillary vessels extended from the meniscosynovial junction into the defect. Subsequently, organized fibrous connective tissue was formed, which had changed to cartilaginous tissue at 12 to 24 weeks. The combination of fibrin sealant and endothelial cell growth factor enhanced the neovascularization and formation of granulation tissue, which accounted for the increased healing level in the avascular portion of the meniscus. PMID- 1443322 TI - Patterns of meniscal injury associated with acute anterior cruciate ligament injury in skiers. AB - To determine if the incidence and patterns of meniscal injury associated with acute anterior cruciate ligament injury in skiers are different from those seen in individuals injured in nonskiing athletic activities, we reviewed the records of 150 patients with acute anterior cruciate ligament injuries. All patients had undergone arthroscopic evaluation within 21 days from the time of injury. There were 75 individuals who were injured while skiing and 75 individuals who sustained an injury in some other high-load athletic activity. Associated meniscal injury was documented at the time of arthroscopy and characterized by location, region, zone, depth, shape, size, and stability. Thirty-one of 75 skiers had an associated meniscal injury as compared to 47 of 75 of the nonskiers. This suggested a strong trend of decreased incidence of meniscal injury in the skier group, but the nonskiers had a higher incidence of major meniscal tears that required repair or partial meniscectomy. The location of the meniscal tear was also significantly different. The incidence of isolated lateral meniscal injury in skiers was higher than in nonskiers. There was a strong trend of increased incidence of medial meniscal involvement in the nonskiers than in the skiers. While there was no difference in the zone or region of tear between the two groups, the skier group was more likely to have a longitudinal tear of the posterior horn of the lateral meniscus. In both groups, lateral meniscal tears were more likely to require conservative treatment or partial meniscectomy while medial meniscal tears were more likely to be repaired than excised. PMID- 1443323 TI - Fluoroscopic evaluation for subtle shoulder instability. AB - Fifty patients with unilateral shoulder symptoms and a variety of diagnoses were evaluated with stress testing of both shoulders under general anesthesia using fluoroscopic documentation just before surgery. An axillary lateral view of the glenohumeral joint was taken in neutral rotation and 90 degrees of abduction; this was termed "neutral position." Anterior and posterior translational stresses were then applied and spot radiographs taken. Measurements were made and the translation was expressed as a percentage of displacement of the humeral head with respect to the glenoid. The asymptomatic side was used as a control. We determined that up to 14% anterior translation and up to 37% posterior translation is normal. Using these guidelines, attempts were made to confirm or predict the presence of stability or instability. Thirty-one patients were correctly identified as stable; 14 were correctly identified as unstable. Three patients with anterior shoulder pain were classified as unstable and found to have Bankart lesions at surgery. Overall, specificity was 100% and sensitivity was 93%. Using discriminant function analysis, a difference score of 10% between the symptomatic and control shoulder was generated. This was useful in eliminating interobserver variations in the examination for predicting stability or instability. We recommend this examination as a valuable adjunct to confirm the presence and direction of shoulder instability and predict subtle instability patterns in patients with recalcitrant undiagnosed shoulder pain. PMID- 1443324 TI - Snow skiing injuries in physically disabled skiers. AB - This study, through retrospective review, examines the injury rate of selected disable skiing populations in general and as compared to able-bodied skiers in areas where comparison was possible. Data on disabled skiers gathered from instructional programs at multiple sites indicate that the disabled skier had a very low rate of injury occurrence. Where comparison could be make, it was found that there was no significant difference in overall injury rates between able bodied and physically disabled skiers. Disabled skiers appear to sustain less severe injuries, and they do not show the trend in increasing injury rates that able-bodied skiers in this study show. In addition, the uphill transport of skiers with a disability who use sit- or mono-skis was examined in one large program and found to be efficient and exceedingly safe, with no injuries reported. A major limitation of this study is the inconsistency in methods of data collection and reporting. There is a need for further prospective studies in the general able-bodied and disabled skiing populations with direct comparisons of rate, location and severity of injury, type of disability, and experience level of the skier. We hope that this study will stimulate more ski areas to allow disabled skiers on their slopes, even it limited to participation in supervised, instructional programs. PMID- 1443325 TI - Healing of the patellar tendon autograft after posterior cruciate ligament reconstruction--a process of ligamentization? An experimental study in a sheep model. AB - Forty-eight skeletally mature sheep underwent posterior cruciate ligament reconstruction with free patellar tendon autografts in one knee; the contralateral knee served as a control. Immediate rehabilitation without immobilization followed. Autograft healing was evaluated by histologic, roentgenographic, and biomechanical techniques up to 2 years postoperatively. After implantation, the autograft tissue underwent necrosis and degeneration, followed by a gradual healing process comprising revascularization, cellular migration, and formation of an extracellular matrix. The autograft bone pegs were osseously incorporated by 6 weeks. After an initial loss of strength, the material properties of the operated knee recovered to only about one-third that of the control. Better alignment of the collagen fiber bundles resulted in increased material properties, up to approximately 50% of the control at 52 weeks. After 2 years, the autograft tissue was found to differ structurally and mechanically from a ligament, suggesting that the autograft may never approach normal ligament characteristics. Degenerative alterations, the wide-spread presence of type III collagen, and abnormal accumulations of glycosaminoglycans in the autograft correlated with a maximum stress of 60% and an elastic modulus of 70% of the control. Although ligamentization was not seen, the staging of autograft healing into different phases based on distinct morphologic manifestations (necrosis, revitalization, collagen formation, and remodeling) and correlating with changing mechanical properties may provide a rationale for rehabilitation protocols with a realistic evaluation of the loading capacity of the replacement tissue. PMID- 1443326 TI - In vitro comparison of over-the-top and through-the-condyle anterior cruciate ligament reconstructions. AB - Knee kinematics, during standard knee examination maneuvers, were measured on 15 fresh cadaveric knees in their normal state and after isolated sectioning of the anterior cruciate ligament using a six degree of freedom electrogoniometer. Proximal iliotibial band autografts were used to perform two anterior cruciate ligament reconstructions on the cadaveric knees: an over-the-top reconstruction and a through-the-condyle procedure. Both of these reconstructions reduced the abnormal anterior translation of the anterior cruciate ligament-deficient knee seen in Lachman testing. However, neither reconstruction restored the normal anterior translation. In addition, other motions remained uncorrected: 1) the internal rotation due to internal torque at full extension; 2) coupled anterior translation during internal rotation at full extension; and 3) coupled medial translation with anterior translation in Lachman testing. There were no statistical differences noted in the joint kinematics created by either reconstruction. PMID- 1443327 TI - Incidence of injury in Texas high school football. AB - This study was undertaken to determine the incidence of injury in high school football based on evaluation of 100 high schools in the State of Texas during a single football season (1989). Certified athletic trainers were the initial medical professionals providing on-site diagnosis and treatment of all injuries. An injury was defined as: 1) an incident causing an athlete to miss all or part of a single practice or game; 2) any incident treated by a physician; and 3) all head injuries reported to the athletic trainer. Data were collected that allowed calculation of the time of exposure to injury per athlete in the sample. There was 75.5% participation in the study by the certified athletic trainers in the 100 schools. A total of 4399 athletes in varsity football programs participated in the study. There were 2228 injuries, as defined in the study, during the period of study, giving an incidence of injury of 0.506 injury per athlete per year. Severe injuries--those requiring hospitalization--were found in 137 cases, for an incidence rate of 0.031 injury per athlete per year. The incidence of reportable defined injury was calculated to be 0.003 injury per hour of exposure per student athlete. The knee was found to be the most commonly injured anatomic site; the ankle ranked second. PMID- 1443328 TI - Human torque velocity adaptations to sprint, endurance, or combined modes of training. AB - We had groups of athletes perform sprint and endurance run training independently or concurrently for 8 weeks to examine the voluntary in vivo mechanical responses to each type of training. Pre- and posttraining angle-specific peak torque during knee extension and flexion were determined at 0, 0.84, 1.65, 2.51, 3.35, 4.19, and 5.03 radian.sec-1 and normalized for lean body mass. Knee extension torque in the sprint-trained group increased across all test velocities, the endurance trained group increased at 2.51, 3.34, 4.19, and 5.03 radian.sec-1, and the group performing the combined training showed no change at any velocity. Knee flexion torque of the sprint and combined groups decreased at 0.84, 1.65, and 2.51 radian.sec-1. Knee flexion torque in the sprint-trained group also decreased at 0 radian.sec-1 and in the combined group at 3.34 radian.sec-1. Knee flexion torque in the endurance-trained group showed no change at any velocity of contraction. Mean knee flexion:extension ratios across the test velocities significantly decreased in the sprint-trained group. Knee extension endurance during 30 seconds of maximal contractions significantly increased in all groups. Only the sprint trained group showed a significant increase in endurance of the knee flexors. These data suggest that changes in the voluntary in vivo mechanical characteristics of knee extensor and flexor skeletal muscles are specific to the type of run training performed. PMID- 1443329 TI - Ruptures of the pectoralis major muscle. An anatomic and clinical analysis. AB - We evaluated 12 patients with 14 ruptures of the pectoralis major muscle to compare surgical and conservative management of this injury. Because 9 of the injuries occurred while weight lifting, we performed an anatomic study on human hemithorax specimens during a simulated bench press to determine the mechanism of this rare occurrence. Excursion of individual pectoralis muscle fibers was measured at seven points along the broad muscle origin by the use of fine wires connected to the humeral insertion and to dial gauges on the study apparatus. Excursions in the concentric and eccentric phases of the lift were expressed as a percentage of resting fiber length. The short, inferior fibers of the muscle lengthened disproportionately during the final 30 degrees of humeral extension. We concluded that the inferior fibers have a mechanical disadvantage in the final portion of the eccentric phase of the lift, and application of high loads to these maximally stretched fibers produces rupture. We repaired five acute and two chronic ruptures, and measured peak torque and work production against the contralateral side using Cybex isokinetic testing. Surgically treated patients showed comparable torque and work measurements, while conservatively treated individuals demonstrated and marked deficit in both peak torque and work/repetition. We recommend repair of complete pectoralis muscle ruptures in active patients who require maximum strength in vocational or avocational activities. PMID- 1443330 TI - Reconstruction of the lateral ankle ligaments. A biomechanical analysis. AB - The purpose of this study was to perform a biomechanical analysis of several commonly performed operative procedures used to stabilize the lateral ankle. We performed the Evans, Watson-Jones, and Chrisman-Snook procedures on 15 cadaveric ankles and tested the ankles for stability, motion, and isometry of graft placement. The Evans procedure allowed increased anterior displacement, internal rotation, and tilt of the talus when compared to ankles with intact ligaments. Subtalar joint motion was restricted by the Evans procedure. The Watson-Jones procedure controlled internal rotation and anterior displacement of the talus, but was less effective in controlling talar tilt and also restricted subtalar joint motion. The Chrisman-Snook procedure allowed increased internal rotation and anterior displacement of the talus when compared to ankles with intact ligaments. The procedure was effective in limiting talar tilt, but restricted subtalar joint motion. Based on the biomechanical data obtained, we devised a lateral ankle reconstruction with bone tunnels that reproduce the anatomic orientation of both the anterior talofibular and calcaneofibular ligaments. This ankle ligament reconstruction resists anterior displacement, internal rotation, and talar tilt without restricting subtalar joint motion. CLINICAL RELEVANCE: We found considerable mechanical differences among the more commonly performed lateral ankle reconstructions. It is possible to locate bone tunnels and graft placement so that a more anatomic configuration is achieved. PMID- 1443331 TI - Ultrasound examination of soft tissue injury of the lower limb in athletes. AB - We performed ultrasonography on 32 athletes complaining of intense pain in a swollen and tender thigh or calf after a contusion or stretching trauma. The ultrasonogram was used to visualize the presence and size of a suspected hematoma. The findings included the following: 7 patients with a circumscribed, anechoic lesion compatible with a liquefied hematoma; 10 patients with a circumscribed lesion of mixed echogenicity compatible with areas of liquefied hematoma, coagulated blood, and edema; and 15 patients with a diffuse change in echogenicity of the whole muscle. The circumscribed liquefied, and mixed hematoma were more common after contusion trauma, while the diffuse type was more common after injury caused by stretching. Ultrasonography is useful in localizing the hematoma and in characterizing the different types. Differentiation is important in diagnosis and choice of treatment. PMID- 1443332 TI - Echographic and Doppler screening of the forearm arteries in professional volleyball players. AB - We evaluated nine professional volleyball players by clinical, echographic, and Doppler technique examination of the forearm and digital arteries to determine vascular damage caused by repeated trauma. The results of these tests showed that one-third of the subjects had vascular lesions in the right hand; only one of these was symptomatic. This suggests that noninvasive screening should be recommended and included in the regular medical check-ups of professional athletes in whom repeated trauma to the hand is likely, such as volleyball players. PMID- 1443333 TI - A biomechanical analysis of solvent-dehydrated and freeze-dried human fascia lata allografts. A preliminary report. AB - This study compares the basic mechanical properties of two groups of commercially available fascia lata allografts processed by different means (solvent-dehydrated and sterilized via gamma radiation, and freeze-dried without secondary sterilization). The results reveal significantly (P less than 0.05) higher stiffness, higher maximum load to failure, and higher maximum load per unit width of graft with the solvent-dried as opposed to the freeze-dried fascia lata. Subsections of individual solvent-dried specimens were also more uniform in their mechanical properties than those of the freeze-dried allografts. CLINICAL RELEVANCE: Fascia lata is used as a graft material in a variety of orthopaedic procedures. Allograft fascia lata offers an increased cross-sectional area of material and eliminates the morbidity associated with the harvesting of autologous tissues. However, the structural uniformity of such large grafts has been questioned. Processing techniques used in the sterilization and storage of such grafts is varied and represents a potential source of variation in the mechanical properties of allograft specimens. The results of this study suggest that a commercially available solvent-dehydrated form of fascia lata provides a more suitable grafting material than freeze-dried specimens obtained from tissue banks. PMID- 1443334 TI - Patellar osteochondral fracture: the unforeseen hazard of golf. PMID- 1443335 TI - Fracture of the supracondylar femur after anterior cruciate ligament reconstruction using patellar tendon and iliotibial band tenodesis. A case report. PMID- 1443336 TI - Lateral plantar nerve entrapment: foot pain in a power lifter. PMID- 1443337 TI - Sudden death in a young athlete. A case report. PMID- 1443338 TI - Purification of native dengue-2 viral proteins and the ability of purified proteins to protect mice. AB - Both the envelope structural protein and the non-structural NS1 protein have been purified from the flavivirus dengue-2 by high-pressure liquid chromatography. These purified proteins maintain their reactivity with monoclonal antibodies. When tested in mice, the envelope protein elicited neutralizing antibodies and partially protected the animals against a lethal viral challenge. The mice responded to the non-structural protein by producing antibodies; however, these antibodies were not neutralizing and the mice were not protected. PMID- 1443339 TI - Antibodies to the major merozoite surface coat protein of Plasmodium falciparum (gp195) in a human population living in a malaria-endemic area of the Philippines. AB - The seroprevalence of naturally acquired antibodies against Plasmodium falciparum merozoite surface protein gp195 was assessed in 726 individuals living in the Napsan region of Palawan in The Philippines. Antibodies against gp195 were detected using parasite-derived antigens in an enzyme-linked immunosorbent assay. The lowest seroprevalence of anti-gp195 antibodies (45%) was found in the 0-4 year-old age group. By 10-19 years of age, the seroprevalence of anti-gp195 antibodies had leveled off at approximately 90%. Anti-gp195 antibody titers were determined for 59 randomly selected individuals using parasite-derived gp195 and two yeast recombinant polypeptides corresponding to the N-terminal (195A) and C terminal (p42) processing fragments of gp195. For each antigen, the lowest antibody titers were found in the 0-4-year-old age group. The 5-9-year-old age group had anti-gp195 antibody titers comparable with the older age groups. Immunoblotting experiments with parasite-derived gp195 revealed that all serum samples tested had detectable antibodies to the 195-kD gp195 precursor molecule and the 83-kD N-terminal processing fragment. Individuals with anti-gp195 titers greater than 1:400 had antibodies against both the N-terminal and C-terminal processing fragments of gp195. These results suggest that the gp195 C-terminal region may be less immunogenic than the N-terminal region when presented on the parasite surface during natural malaria infections. PMID- 1443340 TI - Characterization of naturally acquired antibodies to the non-repetitive flanking regions of the circumsporozoite protein of Plasmodium falciparum. AB - Antibody responses to the circumsporozoite (CS) protein of Plasmodium falciparum have previously been reported against the central repeating tetrapeptides of this protein. Segments of the protein flanking the repeat region also contain B-cell epitopes, but specific antibody responses have not been previously characterized. Longitudinal serum sets from 16 Thai adults who developed acute falciparum malaria were selected to represent a spectrum of antibody response to the repeat region (R32). These sera were assayed by enzyme-linked immunosorbent assay using as capture antigen a recombinant fusion protein, NS1(81)RLF, which contains both flanking regions, but lacks the NANP and NVDP repeats of the P. falciparum CS protein. Antibody responses to the repeatless flanking (RLF) regions were observed in all subjects, including five individuals who lacked detectable anti R32 antibody responses. Anti-RLF antibody responses induced by natural infection appear to be short-lived and of low-to-moderate magnitude. Thus, if anti-RLF antibodies prove to be protective, derived vaccine candidates may require presentation of these epitopes with adjuvants or delivery systems that enhance immunogenicity. PMID- 1443341 TI - Rapid in vivo detection of chloroquine resistance by the Quantitative Buffy Coat Malaria Diagnosis System. AB - The use of the Giemsa-stained thick blood smear for the diagnosis of malaria has not been supplanted since the discovery of the parasite by A. Laveran in 1880. Recently, a new direct diagnosis technique, the Quantitative Buffy Coat (QBC)* Malaria Diagnosis System, has been developed. We compared this technique with the thick blood smear diagnosis in a study of the efficacy of chloroquine therapy in Zaire. A total of 815 subjects were screened; 71 participated in the trial. They were given chloroquine at a dose of 25 mg/kg of body weight over three days and were examined for parasitemia two and seven days after treatment. Chloroquine resistance was detected in 38% of the subjects by thick blood smear and in 45% by the QBC test. Of greater interest was the time required for each diagnosis: an average of 17 min was required to examine microscopic fields with 1,000 leukocytes by thick blood smear analysis compared with less than one min by the QBC system. In addition, we did not observe diminished attention from fatigue by microscopists using the QBC system despite the large number of tests conducted. We conclude that the QBC system is an important tool for studies of drug resistance. PMID- 1443342 TI - Detection of Cryptosporidium parvum DNA in fixed, paraffin-embedded tissue by the polymerase chain reaction. AB - The objective of this project was to demonstrate detection of Cryptosporidium parvum DNA in fixed, paraffin-embedded tissue using the polymerase chain reaction (PCR). DNA was purified from six samples of fixed, paraffin-embedded tissue that were histologically positive for C. parvum and used in the PCR. Previously developed oligonucleotide primers specific for C. parvum were used to amplify a 452-base target sequence, and a 20-base synthetic probe labeled with digoxigenin 11-dUTP was used to detect the amplification product by chemiluminescence. All six samples were positive by PCR; negative controls showed no amplification or hybridization. This approach could provide a sensitive and specific method for detection of parasite material in fixed, paraffin-embedded tissue samples, and prove to be of significant value in retrospective studies of archival material. PMID- 1443343 TI - Diagnosis of Encephalitozoon cuniculi infection by western blot and the use of cross-reactive antigens for the possible detection of microsporidiosis in humans. AB - Microsporidia are very primitive, eukaryotic, obligate, intracellular, protozoan parasites. Encephalitozoon cuniculi, a microsporidian originally described from a rabbit infection, has been described in humans as well as in many species of laboratory animals. We report the detection of E. cuniculi by Western blotting in a rabbit with torticollis that was obtained from an Encephalitozoon-free colony. Cross-reactivity of this serum was observed with antigens prepared from several genera of microsporidia. Identical Western blotting patterns were obtained with sera obtained from a rabbit immunized with E. cuniculi that was purified from tissue culture cells. In addition, we were able to demonstrate cross-reactivity between E. cuniculi rabbit antisera and Enterocytozoon bieneusi antigens by indirect immunofluorescent assay techniques in human intestinal biopsy samples. These cross-reactions between microsporidia may be useful in developing diagnostic tests for non-cultivatable microsporidia such as Enterocytozoon bieneusi. PMID- 1443344 TI - Improved diagnostic performance of the circulating antigen assay in human schistosomiasis by parallel testing for circulating anodic and cathodic antigens in serum and urine. AB - Serum and urine levels of two Schistosoma circulating antigens, the circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA), were determined by monoclonal antibody-based enzyme-linked immunosorbent assays in 56 Egyptian patients infected with S. mansoni and in 12 patients infected with both S. mansoni and S. haematobium. Both CAA and CCA could be specifically demonstrated in 82% and 88% of the serum samples and in 88% and 87% of the urine samples, respectively. While complete specificity was maintained, sensitivity was increased to a range of 91-98% by parallel use of the two circulating antigen assays, i.e., an individual with a positive titer for at least one of the assays was considered to be infected. A combination of CAA and CCA determinations in urine samples only resulted in a sensitivity of 94%. However, the highest sensitivity was achieved when the serum-CCA assay was combined with the urine-CCA assay (98%) or with the urine-CAA assay (97%). Sensitivity could not be increased further by combining more than two tests. A significant correlation was demonstrated between the level of circulating antigen and the number of parasite eggs in feces in each of the four assays. In addition, the levels of CAA and CCA in serum and urine were significantly correlated with each other. Our results indicate that diagnosis of schistosome infections by detection of circulating antigens can be significantly improved by parallel testing for multiple antigens. PMID- 1443345 TI - Tuberculous peritonitis in Egypt: the value of laparoscopy in diagnosis. AB - Abdominal laparoscopy was performed on 200 patients with undiagnosed ascites. It was unsuccessful in one patient with tuberculous peritonitis because of extensive adhesions. A presumptive diagnosis of tuberculous peritonitis based on clinical findings and peritoneal tubercles or adhesions visualized during laparoscopy was made in 90 of these patients. The diagnosis was confirmed in 88 by histopathology, bacteriology, or therapeutic response. Two of the 109 remaining patients who had other presumptive diagnoses made during laparoscopy were eventually confirmed to be cases of tuberculous peritonitis. Of 91 patients with tuberculous peritonitis included in this series, 79% were females, with the majority (79%) of them being of child-bearing age. Half had been ill for longer than one month. The most frequent complaints were abdominal pain, fever, anorexia, night sweats, abdominal swelling, and weight loss. Ascites, fever, wasting, pallor, and abdominal tenderness were common findings. Ultrasonography demonstrated ascites in all patients who underwent this procedure; 21% also had adhesions. Pleural effusion was present in 15% and pulmonary tuberculosis was detected in only two patients. Biopsy samples taken during laparoscopy showed that 60% had noncaseous granulomas and 33% had caseous granulomas. Mycobacterium tuberculosis was detected in 77%, with guinea pig inoculation having the highest sensitivity, followed by culture, and lastly by acid-fast smear. Mycobacterium tuberculosis was isolated more easily from biopsy samples than from ascitic fluid. Nine of 20 M. tuberculosis isolates that were identified as to species were M. bovis. Tuberculous peritonitis, a frequent cause of febrile ascites in Egyptian women, was easily diagnosed by histopathologic and bacteriologic studies of biopsy samples taken at laparoscopy. All patients responded rapidly to antituberculosis therapy. PMID- 1443346 TI - Field evaluation of an enzyme-linked immunosorbent assay for estimating the sporozoite rate in Anopheles albimanus. AB - We have verified for specimens of Anopheles albimanus that an enzyme-linked immunosorbent assay (ELISA) used to assess Plasmodium vivax and P. falciparum sporozoite antigen rates gives results comparable to the salivary gland dissection method for estimating sporozoite rates. For 14,150 adults of An. albimanus, captured at five locations in Guatemala, we report sporozoite antigen rates of 0.03-0.57%, which correlate with the malaria prevalences at the study sites. We also present data that suggest that specimens of An. albimanus for the ELISA can be obtained more efficiently by cattle corral collections than by the human bait capture method. PMID- 1443347 TI - Effect of Plasmodium falciparum on blood feeding behavior of naturally infected Anopheles mosquitoes in western Kenya. AB - Feeding behavior was compared between infected and uninfected field-collected groups of Anopheles gambiae sensu lato and An. funestus from western Kenya. A significantly greater percentage (81%) of Plasmodium falciparum-infected An. gambiae s.l. females probed on experimental hosts (hamsters) than did uninfected females (38%). Among those females that initiated probing, there was no effect of infection status on the ability to take a bloodmeal. Plasmodium falciparum infected An. gambiae s.l. probed more often (mean = 4.0) and for a longer time (mean = 277 sec) than did their uninfected counterparts (mean = 2.4 probes and mean probing time = 214 sec). Results for the small number of An. funestus that fed followed the same trend. Among infected An. gambiae s.l. females, there was no effect of sporozoite density on either the number of probes made or the total probing time. Among uninfected females, there was no difference in feeding behavior between nulliparous and parous females. In laboratory experiments, female age had no effect on blood-feeding behavior. Our findings provide evidence that natural malaria infection modifies the feeding behavior of Anopheles females. PMID- 1443348 TI - Circumsporozoite antibody as a serologic marker of Plasmodium falciparum transmission. AB - In a longitudinal study of a malaria-endemic village in southeastern Thailand, circumsporozoite (CS) antibody to sporozoites of Plasmodium falciparum was measured by an enzyme-linked immunosorbent assay to determine its usefulness as a seroepidemiologic marker of malaria transmission. The CS anti-(NANP)n antibody level and prevalence during a 25-month period paralleled the pattern of seasonal transmission consistent with conventional parasitologic and entomologic measurements. The prevalence and level of antibody decreased during the non transmission wet season, and increased over a 1-2-month transition period between the end of monsoon rains and the onset of dry conditions, an interval of maximum vector activity. Antibody increased with age in the population. The prevalence of antibody to the asexual blood stage as measured by conventional indirect fluorescent antibody assay did not coincide with changes in transmission and was sustained throughout the study period. Thus, CS antibody appeared to reflect the relative population exposure to mosquito inoculation of P. falciparum sporozoites and provided a useful measure of malaria transmission dynamics. PMID- 1443349 TI - Schistosoma mansoni infection in diapausing Biomphalaria glabrata snails: studies of temperature and genetic influences on diapausing behavior. AB - Snails that are capable of undergoing diapause can circumvent unfavorable environmental conditions, including long periods of drought. Studies were performed to investigate possible temperature and/or genetic factors that may trigger lamella formation and diapausing behavior. The influence of diapause in Biomphalaria glabrata snails on susceptibility to Schistosoma mansoni infection and levels of cercarial production was also investigated. Rearing temperatures of 23 degrees C or higher did not induce lamella formation or diapause, regardless of the parental phenotype. However, substantial percentages of progeny from lamellated or lamellated/diapausing parental snails developed lamellae at 18 degrees C and underwent diapause. Only a small percentage of offspring from nonlamellated parents formed lamellae at this temperature. Juvenile snails exposed just prior to diapause, or immediately following a diapause period of three weeks, were highly susceptible to infection by S. mansoni miracidia. Snails that underwent diapause produced comparable or only slightly fewer cercariae than did nondiapausing snails. These studies indicate that diapause in B. glabrata does little to decrease a snail's ability to act as an intermediate host for S. mansoni or to interrupt the development of the parasite. For these reasons, we believe that greater attention should be given to diapausing snail populations when planning field surveys or mollusciciding programs. PMID- 1443350 TI - Albendazole in the treatment of onchocerciasis: double-blind clinical trial in Venezuela. AB - A double-blind clinical trial was conducted in Monagas State, Venezuela to assess the tolerance and efficacy of albendazole in the therapy of Onchocerca volvulus infection. Forty-nine patients (26 treated and 23 controls) received a 10-day course of albendazole (400 mg/day) or a placebo. Consistent with the excellent tolerance observed, albendazole did not kill microfilariae. However, analysis of changes in microfilarial densities (mf/mg of skin) over one year showed that albendazole was active against O. volvulus, presumably by interfering with embryogenesis. The nature, degree, and duration of this effect remain to be determined. PMID- 1443351 TI - In vitro activity of halofantrine and its relationship to other standard antimalarial drugs against African isolates and clones of Plasmodium falciparum. AB - The in vitro activity of halofantrine was studied in chloroquine-susceptible and chloroquine-resistant African clones of Plasmodium falciparum over a period of six months. The susceptibility level remained stable in both clones. The chloroquine-susceptible clone (50% inhibitory concentration [IC50] 6.88 nM) was less susceptible to halofantrine than the chloroquine-resistant clone (IC50 2.98 nM). Using an isotopic semimicro drug susceptibility test, the in vitro activity of halofantrine was compared with the activities of chloroquine, quinine, and mefloquine to study the cross-resistance patterns against 76 African isolates of P. falciparum isolated from cases of malaria imported into France. Chloroquine resistant isolates (n = 47) were significantly less susceptible to quinine (IC50 234 nM), but were more susceptible to both mefloquine (IC50 3.20 nM) and halofantrine (IC50 1.14 nM) compared with the chloroquine-susceptible isolates (n = 29; IC50 147 nM for quinine, 7.16 nM for mefloquine, and 2.62 nM for halofantrine). A significant positive correlation was found between the activities of chloroquine and quinine and between those of mefloquine and halofantrine, indicating cross-resistance between these drugs, while a negative correlation was observed between chloroquine and mefloquine or halofantrine. The responses to quinine and mefloquine or halofantrine showed no correlation with each other. These results reinforce the importance of a cautious use of antimalarial drugs in Africa. PMID- 1443352 TI - A Symposium: Antibiotic Prophylaxis for Surgical Infections. PMID- 1443353 TI - Comparative study of single-dose cefotaxime and multiple doses of cefoxitin and cefazolin as prophylaxis in gynecologic surgery. AB - In this comparative, randomized, multicenter trial, 273 patients scheduled for gynecologic surgery were studied: 87 received a single 1-g dose of cefotaxime 30 minutes before surgery; 81 were given a 1-g dose of cefoxitin 30 minutes before surgery and 1 g every 6 hours for 24 hours after surgery (total dose 4 g); and 105 received a 1-g dose of cefazolin 30 minutes before surgery, followed by 1 g every 8 hours for 48 hours (total dose 6 g). Patients who received cefotaxime had a significantly lower incidence of postoperative fever compared with those treated with cefoxitin or cefazolin (p < 0.01). The incidence of positive urinary cultures was lower in the cefotaxime and cefazolin groups when compared with the cefoxitin group (p < 0.01 and p < 0.05, respectively). The results of this study confirm the efficacy of cefotaxime as prophylaxis in surgical infections and demonstrate that single-dose cefotaxime is more effective than a four-dose regimen of cefoxitin. PMID- 1443354 TI - New clinical data on the prophylaxis of infections in abdominal, gynecologic, and urologic surgery. Multicenter Study Group. AB - Two dose schedules of the antibiotic cefotaxime were compared in a prospective, randomized 226-center study of 3,670 patients undergoing abdominal, gynecologic, and urologic surgery. Schedule A consisted of a single preoperative dose and schedule B consisted of one preoperative dose followed by two postoperative doses. There was no significant difference in the frequency of wound infection or bacteriuria between the two schedules. Schedule B was associated with a significantly higher incidence of postoperative pyrexia, further antibiotic therapy, local side effects, and extended hospital stay. One dose probably has less impact on the intestinal flora. Therefore, single-dose cefotaxime is as effective and less costly when compared with multiple-dose cefotaxime for common surgical procedures lasting less than 3 hours. PMID- 1443355 TI - Which prophylactic regimen for which surgical procedure? AB - For optimal prevention of infection subsequent to a surgical intervention, it is necessary to follow a series of general principles, including the classification of the type of surgical intervention, the characteristics of the antibiotic used, and the route and the time of its administration. Moreover, with reference to the different types of surgery, other factors assume importance: the etiology of the infection and the ability of the antibiotic to achieve adequate levels in the tissues at the beginning of the infective process. In general abdominal, biliary, and obstetric-gynecologic surgery, which covers many clean-contaminated and contaminated interventions for which antibiotic prophylaxis has been shown to be the most effective, the etiology is often mixed (aerobic and anaerobic flora) with a predominance of gram-negative microorganisms. Thus, an appropriate prophylactic regimen must consider a third-generation cephalosporin, such as cefotaxime, that is effective against most gram-negative bacteria, in particular against Klebsiella pneumoniae. Acylureido penicillins can also be used because of their activity against enterococci, gram-positive microorganisms that are also causes of infection in this area of surgical intervention. Combining an antimicrobial such as clindamycin or metronidazole, which are particularly active against anaerobes, may be recommended as well. In urologic surgery, most infections are caused by Enterobacteriaceae; in addition to the antimicrobial spectrum, the ability of the antibiotic to concentrate adequately in the urine and renal tissue must also be considered. Beta-lactam antibiotics are the agents of choice, in particular, third-generation cephalosporins, aztreonam, and acylureido penicillins. In cardiac, orthopedic, and partially in neurologic surgery, where most infections are due to gram-positive bacteria (primarily methicillin-resistant staphylococci), antibiotic prophylaxis should include a glycopeptide agent (teicoplanin, vancomycin). In the field of surgical prophylaxis, more experience has been accumulated with cefotaxime, used as a short-course regimen or as a convenient single dose, than with any other newer cephalosporin. Cefotaxime's broad spectrum of action provides coverage against most potential pathogens and, when used as a single dose, is both convenient and cost-effective. PMID- 1443356 TI - Timing of antibiotic prophylaxis with cefotaxime for prostatic resection: better in the operative period or at urethral catheter removal? AB - There are two critical moments for the development of severe infectious complications following transurethral prostatectomy (TURP): the operative and immediate postoperative periods, and the day that the postoperative drainage catheter is removed. To optimize the timing of antibiotic prophylaxis with cefotaxime, two prospective randomized studies were conducted in patients with preoperatively sterile urine. In Study 1, all patients (n = 50) received cefotaxime 1 g intramuscular (i.m.) 1 hour preoperatively and were then randomized to receive either a second identical dose of cefotaxime 1 hour before catheter removal 24 hours later, or no further antibiotic treatment. In Study 2, patients (n = 89) were randomized to receive either cefotaxime 1 g i.m. 1 hour preoperatively or no preoperative antibiotic, after which all received cefotaxime 1 g i.m. 1 hour before catheter removal. Results were compared using identical evaluation criteria for infection in both studies: incidence of fever (temperature > 38 degrees C), bacteriuria (10(5) organisms/mL) and positive blood cultures, and duration of hospital stay (days). In Study 1, infection was significantly reduced with respect to all parameters in the group receiving two doses of cefotaxime, and total drug treatment costs were halved. In Study 2, the groups did not differ with respect to any parameter. We conclude that a single dose of cefotaxime 1 g i.m. 1 hour preoperatively provides inadequate cover for urethral catheter removal 24 hours later, and that prophylaxis with a single dose of cefotaxime 1 g i.m. 1 hour before catheter removal is just as effective as two doses given 1 hour preoperatively and 1 hour before catheter removal. Prophylactic coverage is essential during the action of removing the catheter and the time immediately following the operation. Long-term antibiotic coverage (24 hours or more) is not necessary. Thus, following TURP in patients with preoperatively sterile urine undergoing continuous bladder irrigation for 24 hours postoperatively, the optimal dose schedule for antibiotic prophylaxis with cefotaxime is a single 1-g dose given i.m. 1 hour before catheter removal. PMID- 1443357 TI - A reassessment of the activity of the third-generation cephalosporins against anaerobes and Staphylococcus aureus. AB - The in vitro activity of cefotaxime (CTX) alone and in combination with its metabolite desacetylcefotaxime (dCTX) was evaluated against 106 isolates of Bacteroides species. and 32 strains of Staphylococcus aureus. All strains were recovered from infected tissues of diabetic patients. Addition of dCTX to the parent compound markedly increased the inhibitory activity against Bacteroides species in general and Bacteroides fragilis and Bacteroides vulgatus in particular. No effect of the combination of both agents on Bacteroides thetaiotaomicron or Bacteroides ovatus was observed; 50% of B. fragilis infections were susceptible to CTX alone and 81% became susceptible to CTX plus dCTX. In addition, a partial synergistic interaction against 20 strains of B. fragilis resulted in a four- to nine-fold reduction in the minimal inhibitory concentration (MIC) after dCTX was added to CTX. Interestingly, 10 of 20 strains that exhibited an MIC of 64-128 micrograms/mL with CTX alone became very susceptible after the combination of parent and metabolite. This favorable positive interaction of both agents was also observed with S. aureus; a two- to four-fold reduction in MIC values was observed when dCTX was added. PMID- 1443358 TI - Cefotaxime is extensively used for surgical prophylaxis. AB - Cefotaxime, a broad-spectrum third-generation cephalosporin, has been extensively used worldwide for chemotherapy of serious infections. Based on the characteristics of its antimicrobial spectrum, low incidence of allergy, and lack of adverse effects, cefotaxime has been used successfully for prophylaxis of a number of different surgical procedures. Extensive data have been accumulated for single-dose or short-course cefotaxime prophylaxis regimens. These cefotaxime regimens have been demonstrated to be very effective and inexpensive. For this article, over 11,500 published cefotaxime prophylaxis cases are reviewed (10,500 control cases) and 98 references are cited. Single-dose cefotaxime was clearly indicated for hysterectomies, cesarean sections, upper gastrointestinal cases, bone and joint operations, biliary tract procedures, transurethral resections, open urologic surgeries, and some vascular procedures. Short-course (3-4 doses) may be required for colorectal resections, cardiac surgeries, head and neck surgeries, organ transplants, specific pediatric surgical cases, and for some patients with compromised immune function, regardless of origin. Cefotaxime has reduced wound morbidity of contaminated abdominal operations to < 10%. This change from multiple-dose regimens to the single-dose or short-course regimens, enabled by cefotaxime use, decreases the risk of inducing or selecting bacterial resistance; the change would generate a significant reduction in hospital costs. Surgeons should not hesitate to employ cefotaxime and other third-generation cephalosporins with proven limited-dose indications to greatly benefit their patients and the hospital environment. PMID- 1443359 TI - Measuring the cost-effectiveness of antibiotic prophylaxis in surgery. AB - Cost-effectiveness analysis is primarily a decision-making aid for budget holders. The first questions that must be answered are: Costs to whom? Effects on whom? Ideally cost-effectiveness analysis should address these questions separately from the perspective of the hospital, the community health services, the patient, and society in general. However, it may not always be practical to perform such a wide-ranging study. Moreover, if the decision maker is primarily concerned with the hospital budget, it is tempting to confine the detailed analysis to items that affect that budget. A good analysis should acknowledge these inevitable limitations and explicitly state whose perspective is being used. Even if a detailed study of community health services is not possible, the analysis should include some evidence about the likely impact of the program on others outside the immediate sphere of the budget holder. Two situations commonly arise in applying cost-effectiveness analysis to surgical prophylaxis: (a) The prophylaxis is more expensive than current practice and its costs must be justified, e.g., the use of a more expensive drug for a recognized indication or the introduction of prophylaxis for a new indication. (b) The prophylaxis is cheaper than current practice and must be shown to be as cost-effective, e.g., the use of a single-dose prophylaxis instead of multiple-dose regimens or the administration of an oral dose instead of an intravenous dose. We believe that cost-effectiveness analysis adds a useful extra dimension to the evaluation of surgical prophylaxis. PMID- 1443360 TI - Current perspectives on antibiotic use in the treatment of surgical infections. AB - Infections that involve the attention of the surgeon include those that require operations for cure as well as those that complicate emergency and elective surgical procedures. Mechanical correction is of paramount importance in the eradication of such infections with antibiotics serving an adjuvant role, primarily to clear lymphatics and prevent bacteremia and seeding of distant sites. Review of the current hospital antibiotic susceptibility profile is important to determine likely sensitivity to expected pathogens. Infection of the urinary tract remains the most common nosocomial infection, but in surgical patients the severe infections are pneumonia, fasciitis, and peritonitis. Often caused by the gram-negative Enterobacteriaceae, empiric broad spectrum antibiotic therapy is initiated after cultures are obtained. Bacterial infection of the respiratory tract is often difficult to diagnose in severely ill patients because the underlying fever, leukocytosis, and chest X-ray changes are often nonspecific. Reliance on sputum gram stain and culture is important to guide antibiotic therapy. Empiric treatment of peritonitis requires knowledge of the normal enteric flora and the likely pathogenic organisms. The most lethal agent against obligate anaerobic organisms is atmospheric oxygen, yet antibiotic coverage against these organisms appears wise, particularly when debridement or resection will be delayed or not performed. Staphylococcus aureus is still the most commonly cultured organism from our Surgical Intensive Care Unit and Burn Unit and S. aureus is often responsible for central line and burn wound infection. For patients in septic shock, we favor administration of a broad spectrum penicillin or cephalosporin combined with an aminoglycoside, with subsequent narrowing of the antibiotic spectrum based on culture results. Antibiotic efficacy, toxicity, efficiency, and cost all must be weighed in the decision-making process. PMID- 1443361 TI - Infections in the surgical setting: epidemiology and effect of treatment with cefotaxime in a multicenter trial including 3,032 patients. AB - Hospital-acquired infections still represent a serious threat to the surgical patient. A nationwide survey of 259 Italian surgical wards involving 11,343 patients was conducted in October 1988. Hospital-acquired infections were recorded in 565 (5%) patients: the microorganisms most commonly involved were gram-negative rods (60% of all isolates), 41% of the infected patients presented one or more intrinsic predisposing factor, and 65% had undergone some invasive procedure. The studied group represented 23% of all surgical patients in the country on the days of the survey. Following the epidemiologic survey, an open multicenter study was conducted in the same wards to evaluate the efficacy and tolerability of cefotaxime (1 g, 2 or 3 times per day) in the treatment of nosocomial surgical infections. Among 3,032 evaluable patients, 1,295 intra abdominal, 610 wound and soft tissue, 554 urinary, and 367 respiratory infections were observed. Treatment was judged to be clinically effective in 94% of patients, and side effects, mostly involving the gastrointestinal tract, were observed in 1.4% of patients; but interruption of the treatment was required only in 19 patients (0.6%). This study confirms that cefotaxime, after over a decade of use, retains high efficacy in the treatment for nosocomial infections and induces a low rate of side effects. PMID- 1443362 TI - Everything you wanted to know about Graves' disease. AB - Graves' disease is an autoimmune thyroid disease characterized by a genetic predisposition, an increased incidence in young women, the presence of thyroid stimulating immunoglobulins, and an uncertain etiology. The onset occasionally follows a frightening episode in the patient's life or separation from a loved one. On physical examination, the patient has a diffuse goiter with secondary hyperthyroidism, a noninfiltrative/infiltrative ophthalmopathy, and, on occasion, an infiltrative dermopathy. Atypical symptoms, signs, and presentations such as "apathetic thyrotoxicosis" are not rare and may delay the diagnosis in some patients. The diagnosis is confirmed by elevations of bound thyroxine (T4), free T4, or bound triiodothyronine in the presence of thyroid-stimulating hormone levels of less than 0.1 mU/L. When the diagnosis is suspected, but unclear, the thyrotropin-releasing hormone stimulation test is indicated. Medical therapy must be long-term when propylthiouracil or methimazole is used, and results in only 25% to 50% remissions at 1 to 2 years. Radioactive iodine therapy has resulted in a need for retreatment in 25% to 33.7% of patients in the past, and hypothyroidism occurs in 70% to 100% of treated patients at 10 years, depending on the dose. Evolving changes in operative technique have led to a 95% to 100% cure rate with complications such as reoperation for hemorrhage (0% to 1.3%), recurrent nerve palsy (0% to 4.5%), and permanent hypocalcemia (0% to 0.6%) at extraordinarily low levels in experienced hands. Greater than 90% of patients have remained euthyroid 2 years after thyroidectomy in several series. Surgery continues to offer the highest cure rate in the shortest period of time. PMID- 1443363 TI - Occult fever in surgical intensive care unit patients is seldom caused by sinusitis. AB - Febrile intensive care unit (ICU) patients were evaluated prospectively for sinusitis. Of 598 admissions, 26 patients with transnasal cannulas, ICU stays over 48 hours, and occult fevers were identified. These 26 underwent physical examinations and sinus computed tomographic (CT) scans. Maxillary centeses and cultures were done in patients with CT abnormalities. Patients with positive scans had nasal tubes removed and received decongestants. Scans were abnormal in 19 (73%). All patients with major CT changes had positive maxillary taps. Most infections were polymicrobial; enteric bacilli were common. Fever resolved with nonoperative care in 18 (95%) patients; in only 1 patient was fever primarily from sinusitis. Sinus CT scans are often abnormal in ICU patients with occult fevers and transnasal cannulas. Pneumatic otoscopy can serve as a screening tool. Most patients respond to nonoperative management. Remote infections are often present. Although radiographic nosocomial ICU sinusitis is common, it is seldom the sole source of fever or the proximate cause of significant morbidity. PMID- 1443364 TI - Are modified radical mastectomies done for T1 breast cancers because of surgeon's advice or patient's choice? AB - Clinical trials show that T1 breast cancers are equally well treated with breast conserving surgery as with modified radical mastectomy. However, the Colorado Central Cancer Registry indicates that, for the past 5 years, the majority of women (72%) with T1 breast cancer in Colorado have undergone modified radical mastectomies. A questionnaire was sent to 175 general surgeons to determine the reasons for the high number of modified radical mastectomies still being performed. The results indicate that one group of surgeons (34% of those responding) believes each type of surgery has equal survival rates but unknowingly influences the patient to choose modified radical mastectomy, with a subtly biased presentation. Education of both surgeons and patients is needed to increase the number of patients with T1 breast lesions who can benefit from breast-conserving therapy. PMID- 1443365 TI - Risk of major elective operation after myocardial revascularization. AB - Although an increased surgical risk of ischemic myocardial disease is widely accepted, amelioration of this risk after coronary artery bypass is poorly defined. We compared the outcomes of major elective general and peripheral vascular operations in 181 patients with prior coronary artery bypass grafting (CABG) with outcomes in an age-, gender-, and procedure-matched group without prior CABG (NOCABG). Despite the perception of a greater operative risk in the CABG patients (more CABG patients in American Society of Anesthesiologists [ASA] class III and fewer in ASA class I, p < 0.001), mortality (1.1% CABG versus 2.8% NOCABG) and morbidity (18.8% CABG versus 18.5% NOCABG) rates in the two groups were not significantly different. For patients who have undergone successful CABG, it appears that: (1) the risk of subsequent elective major general and vascular surgical operations is similar to that of an age-, gender-, and procedure-matched cohort, and (2) the mortality rate after elective operations is low. PMID- 1443366 TI - Advantages of the Papillon protocol in the preoperative treatment of rectal carcinoma. AB - Standard treatment for advanced rectal carcinoma currently includes surgery, radiotherapy, and chemotherapy. Although there are theoretic advantages to preoperative irradiation, it is often not performed because of the prolonged delay of surgery and the purported increase in perioperative complications. A pilot study was undertaken at our institution to evaluate a treatment protocol advocated by Dr. Papillon that offers a shorter treatment time and less patient morbidity than conventional preoperative therapy for rectal carcinoma. Twenty patients with rectal cancer underwent the preoperative regimen that consisted of 3,000 cGy delivered in 10 fractions over 12 days with concomitant 5-fluorouracil and mitomycin-C. Complications were acceptable. Local recurrence was lower than in most reported trials, and survival rates were comparable. Additional benefits of the protocol include lower radiation morbidity to the patient and a decreased delay between diagnosis and surgery. PMID- 1443367 TI - Virulent diverticular disease in young obese men. AB - Recent treatment of young patients (aged 40 years or less) with complicated diverticulitis prompted us to review our experience. During a 9-year period ending in December 1990, 61 of 238 patients treated for acute diverticulitis were 40 years of age or younger. The younger patients were primarily obese Hispanic males in whom the correct diagnosis was frequently missed. Younger patients more frequently required an operation on an urgent basis for complications of diverticulitis during the initial hospitalization. The most common indication for operation in young patients was perforation compared with recurrent disease for the older age group. The younger group had a sevenfold incidence of enteric fistulas complicating their acute episode of diverticulitis. Our data suggest that diverticular disease in young patients is more common and more likely to require early surgical intervention than previously noted. In addition, obesity may represent an important etiologic factor in the development of diverticular disease. PMID- 1443368 TI - Reoperation in patients with the short bowel syndrome. AB - The clinical courses of 53 adult patients with the short bowel syndrome (SBS) were evaluated to determine the incidence of and indications for reoperation. Mesenteric vascular disease (23 patients) and malignancy/irradiation (18 patients) were the most frequent causes of resection. Early reoperation was necessary in nine (17%) patients, primarily for intestinal complications. Twenty (53%) of the 38 patients leaving the hospital required a later abdominal procedure during the mean follow-up of 30 months (range: 2 to 108 months). Three (33%) of nine patients with ulcer disease had gastric resection. Six (21%) of 28 patients at risk for cholelithiasis developed symptoms. Four of these patients underwent cholecystectomy, and three others had a prophylactic cholecystectomy. Ten patients underwent ostomy closure or formation. Intestinal disease necessitated stricturoplasty (three), serosal patch (one), minimal resection (three), or takedown of an ileal conduit (one). Twenty-four (63%) of 38 patients with SBS received home total parenteral nutrition for a mean of 22 months (range: 2 to 105 months). Eleven patients required more than 1 vascular access procedure, and 4 had more than 3 procedures. Patients with the SBS frequently require reoperation for intestinal conditions, cholelithiasis, peptic ulceration, and vascular access. Prophylactic cholecystectomy and strategies for preserving intestinal length are important considerations in these patients. PMID- 1443369 TI - A case-control study of late recurrence of malignant melanoma. AB - Late recurrence of malignant melanoma is uncommon but appears to be a growing problem. It is unclear whether late recurrence has a better prognosis than early recurrence. Since the answer may influence treatment, we compared recurrence sites and subsequent survival in 35 patients with disease-free intervals of 72 to 240 months (median: 127 months) with 35 case-controls who had relapse at 4 to 56 months (median: 26.7 months). The distribution of recurrence sites in early relapse was 66% in regional nodes or soft tissue and 34% in distant soft tissue or viscera. In late relapse, this distribution was 49% in regional nodes or soft tissue and 51% in distant soft tissue or viscera (no significant differences). Median survival for patients with early and late recurrences in regional nodes or soft tissue was 26 and 44 months, respectively (no significant differences); 5 year survival was 27% and 33%, respectively (no significant differences). Median survival was similar for early or late relapse in distant soft tissue or viscera (8 and 10 months, respectively), as was 5-year survival (0% and 6%, respectively). These results suggest that the metastatic pattern and survival after recurrence are similar for patients with early and late recurring melanoma. PMID- 1443370 TI - Operative morbidity and risk factor assessment in melanoma patients undergoing inguinal lymph node dissection. AB - A series of 168 patients who underwent 177 inguinal lymph node dissections from 1979 to 1989 were retrospectively reviewed to determine the incidence and severity of postoperative complications as well as the perioperative risk factors associated with them. Operative mortality was 0%, whereas the incidence of moderate to severe wound infection was 11%, skin flap problems 0%, seromas 6%, and hemorrhage 3%. The occurrence of a wound complication increased the average hospital stay from 11 to 12 days. Multivariate risk factor analysis revealed age older than 50, male sex, and smoking to be significant risk factors for developing a wound infection. The use of prophylactic antibiotics and the duration of closed suction catheter drainage were not predictive of wound complications. Overall, 44% of patients experienced some postoperative edema, with only 7% of patients having 1+ edema that lasted longer than 6 months. Combined ilioinguinal lymph node dissection increased the chance of developing moderate to severe edema. These risk factors identify patients at high risk for morbidity, which should lead to improved perioperative care. PMID- 1443371 TI - The elderly burn patient. AB - During a 16-year period, 547 patients who were older than 64 years of age with a mean total body surface area (TBSA) (third-degree burns) of 25% were treated. Etiologies were flame/flash in 81% of patients, scald in 11%, solids in 7%, and electrical/chemical in 1%. Seventeen percent of patients had significant causal factors. An inhalation injury was present in 13% of patients, and the mortality in these patients was 100%. Burn excision was performed 239 times in 165 patients. The majority of excisions were for full-thickness burns. Excision did not improve overall survival in patients with third-degree burns of 0% to 10%, but the length of stay (LOS) in excised and nonexcised survivors was improved (9 versus 21 days, respectively). The LOS and survival were not significantly different in patients with burns between 11% and 20%. Postburn complications occurred in 28% of patients. Overall mortality was 50% (mean age: 77 years; TBSA: 40%). There were no survivors with over 47% TBSA burns. The leading cause of death was pulmonary sepsis. Most surviving patients returned to a satisfactory lifestyle after discharge. PMID- 1443372 TI - Management of blunt hepatic injuries. AB - Sixty-three consecutive patients with blunt hepatic trauma were examined. Twenty four patients underwent immediate operation, and 39 patients were evaluated by computed tomography (CT), of whom 17 underwent operation. Ten patients had no hepatic abnormalities on CT and had operations for associated injuries. Liver injuries were noted in the remaining seven patients, but CT underestimated the injury in four patients. A large hemoperitoneum was present in all seven patients by CT, and the average transfusion was 10 U during initial resuscitation. Twenty two patients with grade I to III injuries and a small to moderate hemoperitoneum were managed nonoperatively. Six of these patients had transfusions during resuscitation. Only one patient received more than 2 U. There were no deaths and no major complications related to the liver injury. Most patients had repeat CT at 1 week, which demonstrated stable or improving injuries. CT may underestimate the degree of liver injury. Nonoperative management is appropriate in stable patients with grade I to III injuries and a small to moderate hemoperitoneum. These patients should require no more than 2 U of blood, and repeat scans should demonstrate a stable injury. PMID- 1443373 TI - Hematuria as a predictor of abdominal injury after blunt trauma. AB - Among the 1,484 patients included in the Renal Trauma Project with evidence of blunt trauma and hematuria, 160 patients were found to have both hematuria and a significant intra-abdominal injury not related to the genitourinary system. The incidence of abdominal injury generally increased with the degree of hematuria, approaching 24% in patients with gross hematuria. For each category of degree of hematuria, patients with shock had a significantly higher incidence of abdominal injury (p < 0.05) than patients without shock. The incidence of abdominal injury in patients with microscopic hematuria and shock was 29%, and it was 65% for patients with both gross hematuria and shock. All patients with gross hematuria after blunt abdominal trauma and all patients with microscopic hematuria and a history of shock should be evaluated for both urologic and extra-renal abdominal injuries. PMID- 1443374 TI - How much monitoring is needed for basilar skull fractures? AB - Basilar skull fractures account for approximately 19% of all skull fractures. There have been little data published concerning the need for intensive care monitoring in this injury. We retrospectively studied 259 patients admitted to our trauma center over an 8-year period with a diagnosis of basilar skull fracture. All patients were evaluated with cranial computed tomographic (CT) scans. These patients were admitted to the trauma service, and neurosurgical consultation was obtained in all cases. The diagnosis was made by clinical signs in 207 patients (80%), by CT scan in 47 (18%), and by plain films in 5 (2%). Ninety-two patients (group I) had intracranial pathology in addition to basilar skull fracture. Twenty-one patients in this group underwent craniotomy. In this group, the morbidity and mortality rates were 11% and 7%, respectively. Forty four patients (group II) had no intracranial pathology and a Glasgow Coma Score (GCS) of less than 13. The morbidity was 2%, and the mortality was 2%. One hundred twenty-three patients (group III) had no intracranial pathology on CT scan and a GCS of 13 or greater. The complication rate in this group was 1%, and there was no neurologically related mortality. Patients who are admitted with a diagnosis of basilar skull fracture and who have a GCS of 13 or greater with no intracranial pathology on CT can be managed without intensive care monitoring. PMID- 1443375 TI - What are the contraindications for laparoscopic cholecystectomy? AB - Acute cholecystitis, morbid obesity, and previous upper abdominal surgery have been reported as relative contraindications to laparoscopic cholecystectomy. An analysis of 706 laparoscopic cholecystectomies performed at our institution was undertaken to determine if these relative contraindications led to increased morbidity, an increased rate of conversion to the open technique, or longer operating time. One hundred ninety-seven patients demonstrated one or more relative contraindications to laparoscopic cholecystectomy. Morbidity was not increased in patients with these risk factors, but conversion to open cholecystectomy was required in a greater percentage of patients with acute cholecystitis. We favor an attempt at laparoscopic cholecystectomy in patients with these risk factors; however, they should be counseled as to the increased risk of conversion to open cholecystectomy in the presence of acute cholecystitis. PMID- 1443376 TI - Parathyroid pathology in an intrathyroidal position. AB - A systematic approach based on the embryology of the parathyroid glands should allow for the appropriate identification of both normal and abnormal glands at the time of parathyroidectomy. The exact role of subtotal thyroidectomy as part of this approach remains in question because of the low incidence of intrathyroidal adenomas reported in the past. From 1978 to 1992, 97 cervical explorations were performed in 96 patients (mean age: 56 years) with hyperparathyroidism. Four patients (4%) were found to have intrathyroidal parathyroid adenomas and were cured by ipsilateral partial or subtotal thyroid lobectomy on the side of a missing gland. One parathyroid adenoma completely replaced the right lobe of the thyroid, whereas two inferior and one superior intrathyroidal adenomas were found in the remaining three patients. The 4% incidence of intrathyroidal adenomas is higher than that reported in most series and suggests that this entity may be a more common cause of failed parathyroid explorations than is currently thought. Ipsilateral thyrotomy or subtotal thyroid lobectomy continues to be a potentially curative procedure for hyperparathyroidism when there is a missing and presumably diseased superior or inferior gland. PMID- 1443377 TI - Efficacy of selective intrabronchial air insufflation in acute lobar collapse. AB - Flexible fiberoptic bronchoscopy (FFB) to remove mucous plugs followed by selective intrabronchial air insufflation (SII) to expand the atelectatic lung was used in 17 surgical intensive care unit (SICU) patients with pulmonary lobar collapse. Thirteen patients were admitted for acute trauma, and the remainder were elderly postoperative patients. Lobar collapses occurred on SICU days 1 to 18 (mean +/- SEM: 5 +/- 1 days), and duration ranged from 4 to 258 hours (mean: 77 +/- 18 hours). Indications for FFB with SII included critical hypoxemia in 5 patients, worsening collapse in 2, and failure to respond to aggressive respiratory care in 10 (59%). FFB with SII was effective in 14 (82%) patients: 10 achieved full lung re-expansion, and 4 partial lung re-expansion. When lobar collapse was of less than 72 hours' duration, 92% (12 of 13) of patients had lungs re-expanded compared with 50% (2 of 4) whose collapse existed for more than 72 hours. The mean PaO2/FIO2 (fraction inspired oxygen) ratio was 135 +/- 18 prior to FFB with SII and increased to 205 +/- 21 after FFB with SII. Complications were minor and clinically insignificant. In conclusion, SII appears to be a simple, safe, effective adjunct to FFB in the treatment of SICU patients with pulmonary lobar collapse. PMID- 1443378 TI - Contribution of routine intraoperative completion arteriography to early infrainguinal bypass patency. AB - To determine the clinical utility of routine intraoperative completion arteriography, we prospectively evaluated 214 consecutive infrainguinal bypass grafts (209 reversed-vein and 5 polytetrafluoroethylene grafts) performed from July 1987 to August 1991. Visual inspection, pulse palpation, and continuous-wave Doppler examination were performed in all cases. At least 1 completion arteriogram was obtained in 213 cases (99%). The bypasses were to the popliteal artery in 130 cases and to the tibial or pedal arteries in 84 cases. Graft patency was confirmed at 30 days in all patients by ankle-brachial index determinations (greater than 0.2 increase) and duplex scan-derived peak-systolic flow velocities (greater than 45 cm/s). Significant technical problems requiring revision were identified in 18 grafts (8%), including 6% of popliteal grafts and 12% of tibial/pedal grafts. Only three of these problems were suspected by pulse palpation or continuous-wave Doppler examination. The intraoperative angiographic findings leading to revision included distal anastomotic stenoses (n = 6), distal arterial disease requiring sequential bypass (n = 4), mid-graft valvular or branch ligature stenoses (n = 4), distal arterial thrombosis (n = 2), and graft kink or twist (n = 2). Thirty-day primary patency was 99% (129 of 130) for femoropopliteal grafts and 93% (78 of 84) for femorodistal grafts. Secondary patency was 100% (130 of 130) and 96% (81 of 84), respectively. Primary patency was 89% (16 of 18) for those grafts that required intraoperative revision based on arteriographic findings. We conclude that routine completion arteriography is an excellent method of ensuring the intraoperative technical adequacy of infrainguinal bypass. The test is easy to perform, reproducible, and should be considered the "gold standard" for intraoperative bypass assessment. Prior to adopting angioscopy or duplex scanning for intraoperative surveillance, randomized, controlled validation studies against angiography should be performed. PMID- 1443379 TI - Effect of surgical manipulation of polytetrafluoroethylene grafts on microstructural properties and healing characteristics. AB - The effects on graft healing of alterations in the microstructure of polytetrafluoroethylene (PTFE) grafts induced by surgical instruments have not been fully elucidated. This study evaluates changes in the structural and physical properties of PTFE grafts resulting from the intentional application of commonly used surgical instruments and the influence of these changes on cellular ingrowth. The extent of cellular ingrowth into intact (10, 30, and 60 microns unreinforced and 30 microns reinforced [R]) and structurally compromised PTFE grafts (30 reinforced and 60 microns nonreinforced) implanted subcutaneously in Sprague-Dawley (n = 14) rats was evaluated at 7 and 21 days. The thrombogenicity of 10-, 30-, 60-, and 80-microns intact graft segments was determined gravimetrically after suspension in the internal jugular vein of dogs for 90 minutes. Cellular ingrowth consisting of fibroblasts, macrophages, and microvessels was directly related to porosity and was most extensive in 60 microns uncompromised graft segments, being 7-, 17-, and 20-fold greater than was observed in 60- and 30R-microns compromised grafts and undamaged 10-microns grafts, respectively. There was a direct relationship between porosity and thrombogenicity of intact graft segments suspended in the jugular vein. The amount of thrombus adherent to 80-microns graft segments was eightfold greater compared with 10-microns grafts. Manipulation of PTFE with surgical instruments significantly impairs healing and may be a possible etiologic factor in the poor long-term performance of these grafts. PMID- 1443380 TI - Vascular complications of the intra-aortic balloon pump. AB - The lower extremity complications of 100 consecutive patients who required the placement of an intra-aortic balloon pump (IABP) during a 3-year period were studied. Indications for the IABP included hypotension during cardiac catheterization (33%) or coronary angioplasty (13%), hemodynamic instability after open heart surgery (35%), unstable angina (5%), and cardiac arrest (14%). The incidence of IABP morbidity was 29%. Complications included ischemia (25%), bleeding (2%), lymph fistula (1%), and femoral neuropathy (1%). Twenty patients required 1 or more surgical interventions for lower extremity vascular complications. The majority of patients who underwent operation (70%) had significant pre-existing arterial occlusive disease. Local femoral artery reconstruction or repair was performed in 18 patients. Two patients had adjunctive bypasses. Continued IABP support was required in four patients after treatment of complications. One patient (1%) had an above-knee amputation. Limb ischemia was treated nonoperatively by removal of the IABP in five patients. Color-flow duplex scans were useful in distinguishing hematomas from pseudoaneurysms as well as for assessing femoral artery flow. We conclude that: (1) limb ischemia remains the primary complication of the IABP; (2) pre-insertion documentation of the severity of existing peripheral arterial disease by noninvasive studies may aid in the management of subsequent acute limb ischemia; (3) femoral artery thrombectomy or endarterectomy is usually sufficient for revascularization; and (4) noninvasive color flow studies are an important diagnostic tool in the nonoperative management of limb complications. PMID- 1443381 TI - Concentration of refluxed acid and esophageal mucosal injury. AB - The hallmark of gastroesophageal reflux disease (GERD) is an increase in esophageal exposure to gastric juice. This exposure can result in complications such as esophagitis, stricture, and Barrett's esophagus. The aim of this study is to determine if there are specific pH exposure patterns that are associated with the development of these complications. The 24-hour esophageal pH data for 50 normal subjects and 154 patients with proven GERD were analyzed for time spent at different pH intervals. Increased esophageal acid exposure at a given interval occurred when the cumulative time of exposure exceeded the 95th percentile of that measured in the 50 normal subjects for that interval. The greatest prevalence of mucosal damage was found in the those patients with increased esophageal exposure to pH 0 to 2, corresponding to the known pKa of pepsin. This exposure was not related to a hypersecretory state. In addition, mucosal injury was associated with an increased esophageal exposure to pH 7 to 8. We conclude that mucosal injury in patients with GERD is related to the exposure time to gastric juice with a pH of less than 2 or greater than 7. PMID- 1443382 TI - Changing clinical spectrum of spontaneous pneumothorax. AB - The epidemiology and etiology of spontaneous pneumothorax (SP) are shifting away from the predominance of subpleural bleb disease as emphasized by most reports since that of Kjaergaard (Sweden, 1932). We conducted a retrospective review of all patients admitted to a large urban hospital with the diagnosis of SP over the past 8 years. Of 120 patients, 32 had the acquired immunodeficiency syndrome (AIDS) (group 1, 26.6%), 43 patients had classic subpleural bleb disease or chronic obstructive pulmonary disease with blebs (group 2, 35.8%), and 45 patients had nonbleb disease exclusive of AIDS (group 3, 37.5%). These three groups were studied with respect to primary success rates with differing modalities of therapy. Bilateral SP occurred in 34% of group 1 patients, 2% of group 2 patients, and 11% of group 3 patients. The in-hospital mortality was 34% in group 1 compared with 2% in group 2 and 4% in group 3. Thirty-four percent of group 1 patients had recurrent SP compared with 16% of group 2 patients and 8% of group 3 patients. This report describes the changing etiology and epidemiology of SP in a large urban hospital from 1983 to 1991 and represents the largest single institution report of AIDS-related pneumothorax. Standardized therapy was shown to have predictably favorable results in patients with bleb disease and nonbleb disease exclusive of AIDS. SP in patients with AIDS was associated with a high mortality rate and primary treatment failure; small-bore catheters and nondrainage therapies have a very limited role in these patients. PMID- 1443383 TI - Conservative versus surgical management of chylothorax. AB - Chylothorax is a potentially life-threatening disorder that has profound respiratory, nutritional, and immunologic consequences. Treatment for this problem is controversial, and the results have been variable. From 1985 to 1990, 29 patients (16 males, 13 females; mean age: 20.1 years; range: 5 days to 76.8 years) were diagnosed as having chylothorax (18 right, 6 left, 5 bilateral). Etiologies included surgical trauma (26) and nonsurgical trauma (3). Initial conservative treatment consisted of tube thoracostomy drainage (mean duration: 13.3 days; range: 1 to 62 days; mean total volume: 4,030 mL) and dietary modification (low-fat diet, total parenteral nutrition). This resulted in resolution of the chylothorax in 23 patients (79% success), although 2 patients died of unrelated causes while hospitalized (myocardial infarction and cardiopulmonary arrest). Five adult patients and one infant (21%) required ligation of the thoracic duct, with resolution of the chylothorax in all six (100% success). Despite successful duct closure, one infant died of respiratory failure unrelated to the operation, and one adult died as the result of a cerebrovascular accident 6 weeks postoperatively, yielding an operative mortality of 33% and an overall mortality of 14% (4 of 29). Our experience demonstrates that initial treatment of chylothorax with thoracostomy drainage and dietary modification is successful in the majority of patients and is not associated with high morbidity or mortality rates. Surgical intervention for chylothoraces that fail to respond to initial conservative measures will be required in a minority of patients but appears to be associated with a higher risk of complications. PMID- 1443384 TI - Diffuse biliary tract injury after orthotopic liver transplantation. AB - An unusual type of diffuse biliary tract injury after liver transplantation that is characterized by multiple intrahepatic biliary strictures, ductal dilatations, fluid collections, or intrahepatic abscesses has been identified. Over a 5-year period, a total of 10 patients (2%) developed diffuse intrahepatic biliary injury with established vascular patency and no obvious source for their biliary tract pathology. All patients received livers preserved in University of Wisconsin solution with a mean preservation time of 16 hours. This biliary tract injury was associated with the presence of severe preservation injury and Roux limb biliary reconstruction. Of the 10 patients, 5 were treated nonoperatively with multiple stricture dilations and stent placements, 3 underwent retransplantation, 1 was treated operatively with hepaticojejunostomy, and 1 died of sepsis. This study suggests that this complication appears to be related to preservation injury and that the etiology may be ischemic in origin. PMID- 1443385 TI - Current experience with renal transplantation across the ABO barrier. AB - Solid organ transplantation has traditionally been governed by the rules of blood group compatibility. Thus, it has been demonstrated that crossing the ABO blood group barrier generally results in hyperacute rejection. However, the A2 subtype of the blood group A is a weaker antigen. Under certain circumstances, organs from donors with blood group A2 can be transplanted across the ABO blood group barrier into recipients of O or B blood type. Since 1986, 33 patients including 24 blood group O and 9 blood group B patients received A2 (30) or A2B (3) donor kidneys. Both cadaver donor (31) and living-related grafts (2) have been undertaken. The mean follow-up since transplantation for the 21 patients with functioning grafts is 36 months, with a 67.2% current graft survival. Immunosuppression for these transplants consisted of azathioprine, prednisone, and cyclosporine, often in combination with prophylactic OKT3 or antilymphocyte globulin as protocol dictated. Special immunosuppressive protocols such as splenectomy or plasmapheresis were not used. The serum of the potential recipient was analyzed for immunoglobulin G (IgG) and immunoglobulin M (IgM) forms of antibody against A1 and A2 red blood cells. There is a strong correlation between a low (less than or equal to 1:8) anti-A1 IgG titer and both early and long-term graft function. Recipients with an IgG titer greater than 1:8 in the pretransplant serum had a much higher incidence of early graft failure. We no longer recommend transplantation of A2 kidneys into O or B recipients with a pretransplant titer of greater than 1:8 but found that recipients with low titers have graft function rates essentially equal to those of ABO-compatible patients. Patients with blood group B have, over time, lower anti-A IgG titers than do blood group O patients. In addition, the graft survival among blood group B patients is 89% compared with 58% among group O recipients. This may be due to the generally low titers found in blood group B recipients. Since instituting a policy in 1988 of not transplanting the kidney when the anti-A IgG titer is greater than 1:8, the survival in O patients is 88%. We recommend the screening of all organ donors with blood group A for the A2 subgroup and believe that transplantation can be safely and successfully performed in certain patients with blood group O or B.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1443386 TI - Surgical complications in solitary pancreas and combined pancreas-kidney transplantations. AB - The benefits of pancreas transplantation (PT) must be weighed against the morbidity associated with the operative procedure and long-term immunosuppression. Over a 32-month period, we performed 73 PTs including 61 combined pancreas-kidney transplants (PKT) and 12 solitary PTs. In the PKT group, 25 reoperations were performed in 18 patients (29.5%) at a mean of 39 +/- 12 days after transplant. In the solitary PT group, 16 reoperations were performed in 8 recipients (66.7%, p = 0.03) at a mean of 87 +/- 12 days after PT (p < 0.01). In the PKT group, pancreas allograft survival was 93.4%. Vascular thrombosis resulted in the loss of two pancreas allografts. In the solitary PT group, pancreas allograft survival was 50% (p < 0.001), with 6 transplant pancreatectomies performed for either infectious (5) or vascular (1) complications. Surgical complications after PT are common (35.6% in this series), occur earlier in patients who undergo PKT, and are more frequent and morbid in patients undergoing solitary PT, especially after a previous kidney transplant. An aggressive surgical approach can lead to a high rate of pancreas allograft salvage without jeopardizing either the patient or the renal allograft. PMID- 1443387 TI - Referred otalgia. AB - Referred otalgia is a challenging symptom, with the burden on the physician to identify the source. Only by careful patient history and physical examination can all causes in this extensive differential diagnosis be excluded. In the absence of primary otologic pathology, referred pain from a head and neck carcinoma must be considered foremost and ruled out. PMID- 1443388 TI - Bone autografting of the craniofacial skeleton: clinical and biological considerations. PMID- 1443389 TI - Superiorly based trapezius flap for emergency carotid artery coverage. PMID- 1443390 TI - Is biofeedback effective for chronic tinnitus? An intensive study with seven subjects. AB - PURPOSE: This study was developed to test the hypothesis that intensive biofeedback and relaxation training may favorably affect chronic tinnitus. PATIENTS AND METHODS: Seven subjects with chronic tinnitus of moderate to severe intensity engaged in an intensive 5-month program of weekly, individual 90 minute sessions. All individuals attained a high standard of proficiency following training by a biofeedback specialist. A biofeedback unit was provided each subject for daily practice. Audiometric matching of tinnitus pitch and loudness and subjective comparisons of tinnitus loudness were conducted before and after every session. RESULT: Audiometric evaluation showed no changes in tinnitus loudness. Nevertheless, all subjects gained satisfaction from the training. Three reported substantial psychological benefits in coping with tinnitus, two described moderate improvement, and two experienced modest gains. CONCLUSIONS: These results highlight the role of psychological factors in tinnitus management and indicate that biofeedback-relaxation training may be useful therapy for coping with stresses of tinnitus. PMID- 1443391 TI - Thyroid dysfunction after radiation therapy in head and neck cancer patients. AB - INTRODUCTION: The reported incidence of hypothyroidism following surgery and/or radiation therapy for head and neck cancer varies widely. Most patients undergo thyroid lobectomy during laryngectomy. Standard radiation treatment portals often include the thyroid gland. The insidious development of hypothyroidism may be misdiagnosed. This study examines the incidence of thyroid dysfunction in the setting of head and neck cancer therapy. MATERIALS AND METHODS: Thyroid function tests were performed on 100 consecutive patients treated in the head and neck tumor clinic. Statistical inferences on proportions were made using chi-square analysis. RESULTS: Therapy included surgery only (10 patients), radiation therapy only (28 patients), and combined therapy (62 patients). These patients experienced thyroid dysfunction in 0%, 29%, and 45% of individuals respectively. These differences were statistically significant (P < .05). The highest rate of dysfunction (69%) was associated with patients undergoing laryngectomy and radiation therapy. When laryngectomy was not performed, thyroid dysfunction occurred in 28%. CONCLUSION: The likelihood of thyroid dysfunction after radiation therapy is high particularly when combined with surgery in which thyroid lobectomy is performed and the contralateral lobe is potentially devascularized. These results suggest that radiation therapy is a primary factor in alteration of thyroid function. We recommend that routine thyroid function testing be part of follow-up of all head and neck cancer patients. PMID- 1443392 TI - Squamous cell carcinoma of the lower lip. AB - PURPOSE: Most patients with squamous cell carcinoma of the lower lip present with early disease and follow a rather indolent clinical course. Determinant 5-year survival rates range from 85% to 95%. This study was undertaken in an attempt to gain insight into the cause of failure in those few patients who develop recurrent disease. PATIENTS AND METHODS: A retrospective review was completed on patients treated between 1964 and 1990. Patients were staged according to the American Joint Committee. Patients with no palpable adenopathy had either a unilateral or bilateral suprahyoid dissection performed. Patients with palpable adenopathy underwent radical neck dissection. All patients were followed for evidence of recurrent disease. RESULTS: The records of 92 patients treated surgically for squamous cell carcinoma of the lower lip were available and complete. Palpable adenopathy was present in 38 patients; however, only 8 of these patients (21%) were histologically positive. Of the 54 patients judged to be free of disease, 3 (5.5%) had histologic evidence of metastasis. Overall, the incidence of cervical metastasis was 12%. CONCLUSION: The incidence of cervical metastasis in patients with squamous cell carcinoma of the lip is low; however, these data suggest that the size of the primary tumor does not correlate closely with predicting the incidence of regional lymph node metastases. PMID- 1443393 TI - Effects of recurrent otitis media in infancy on auditory perception and speech. AB - INTRODUCTION: Recurrent otitis media is commonly encountered in children before 3 years of age. Conductive hearing loss up to 40 dB is frequently associated with suppurative otitis media. Good hearing is believed to be critical to the development of normal language. This study was undertaken to evaluate the effect of recurrent otitis media on auditory perception and speech. PATIENTS AND METHODS: The experimental group consisted of 33 children with a history of at least three episodes of acute otitis media before 2 years of age. A control group of 29 children experienced one or fewer episodes of otitis media in the first 2 years of age. At the time of investigation, all children were 8 to 10 years of age and had attended similar pre-school, kindergarten, and elementary school programs. None showed evidence of mental retardation nor behavioral or emotional disorders. Speech ability was assessed by a battery of tests specific for Slovene language. Subtests of the Wechsler Intelligence Scale for Children were used as well as the Reading and Writing Test. RESULTS: Auditory perception disorders were evident in 88% of children investigated who had a history of at least three episodes of otitis media by 2 years of age. Decreased auditory stimulation during the time of auditory maturation could prevent the development of these functions completely. No statistically significant differences were observed in the development of articulation. These observations underscore the importance of early management of recurrent otitis media during the first 2 years of age. PMID- 1443394 TI - Thornwaldt cysts. PMID- 1443395 TI - Tympanogenic labyrinthitis and meningitis. PMID- 1443396 TI - Complications of endoscopic sinus surgery. PMID- 1443397 TI - Neuronal ceroid-lipofuscinoses: the current status. AB - In view of the epidemiological connotation of childhood neuronal ceroid lipofuscinosis (NCL) as one of the most frequent progressive lysosomal diseases and neurodegenerative disorders in children, the recognition of the individual clinical forms of childhood NCL is still based on invasive diagnostic electronmicroscopy which, currently, may be applied also for prenatal diagnosis. Like other inherited disorders, the NCL group has finally also benefited from the genetic breakthroughs of localization of the genes for infantile NCL and juvenile NCL on chromosomes 1 and 16, respectively. This review concerns recent advances in morphological studies, broadening of the clinical spectrum of childhood NCL, new biochemical findings, and preliminary therapeutic results. Hereditary animal models, largely for human juvenile NCL, have been successfully employed in elucidation of the nosology of NCL, but the basic defect in human, canine and ovine NCL remains unknown. PMID- 1443398 TI - Myelination of the optic radiation in Leber congenital amaurosis. AB - We have studied the myelination of the visual pathway by magnetic resonance imaging in seven children (aged 5 months to 16 years) with Leber congenital amaurosis. The corpus geniculatum laterale and the retrogeniculate optic radiation had a normal appearance on MRI in all patients. Therefore we conclude that normal myelination of the optic radiation, as it can be grossly assessed by MRI, can take place even with absent or greatly reduced visual sensory input. PMID- 1443399 TI - Epileptic electroencephalographic abnormalities and developmental dysphasias: a study of 32 patients. AB - The relationships between severe developmental dysphasias and epilepsy were analysed in 32 patients with congenital dysphasias. The mean age was 8 years 2 months; 19 of 32 had never had seizures; 9 had had occasional seizures; 4 were epileptic. Twenty-two of 32 had normal repeated standard EEGs, but 10 (2 of which never had seizures) showed epileptic interictal discharges. During prolonged EEG after sleep deprivation, epileptic abnormalities were observed in 13 of the 32 cases (4 of which never had seizures). The overall night sleep recordings showed epileptic abnormalities in 30 of the 32 cases (17 of which had never had seizures). The epileptic interictal abnormalities varied considerably in intensity and aspect in the same patient from one examination to another. Developmentally aphasic children show a higher incidence of abnormal EEG than expected, particularly during overall night recordings. In most cases, the physiopathology of the language disturbance might be identical to that in Landau Kleffner syndrome. PMID- 1443400 TI - Serum creatine-kinase-BB concentration in very low birth weight babies with posthemorrhagic ventricular dilatation. AB - The association between measurements of lateral ventricle dilatation determined by serial ultrasound and brain specific creatine-kinase isoenzyme patterns (CK BB) is studied in 60 very low birth weight preterm neonates of 1,500 g birth weight or 32 weeks gestation or less. The patients were divided into three groups according to cranial ultrasonographic findings: Group A (n = 20) had isolated peri-intraventricular hemorrhage (PIVH); group B (n = 20) had PIVH and dilated ventricles (VM); group C (n = 20) were normal matched preterms and formed the control group. Compared to control babies or those with isolated PIVH, high serum concentrations of CK-BB were observed after birth in babies with persistent dilated ventricles at two weeks postnatal age (p less than 0.01). No difference was found between CK-BB levels of babies with isolated PIVH and control group (p greater than 0.05). We suggest that an elevated CK-BB value is found in babies with persistent ventricular dilatation suggesting severe and diffuse brain damage after post-hemorrhagic ventriculomegaly (VM). PMID- 1443401 TI - Relationship between benign epilepsy of children with centro-temporal EEG foci and febrile convulsions. AB - In order to clarify the relationship between benign epilepsy of children with centro-temporal EEG foci (BECCT) and febrile convulsions (FC), we compared the previous and family histories of FC of one hundred children with BECCT, aged 3 years to 13 years, with those of 100 non-epileptic controls matched for age and sex. The incidences of FC in children with BECCT and non-epileptic controls were 18% and 8%, respectively (P less than 0.05). Forty-eight children (48%) with BECCT and 21 (21%) non-epileptic controls had positive family histories of FC within third-degree relatives (P less than 0.001). Of the fourteen pairs of siblings, one of each having BECCT and the other FC, we conducted an EEG examination in 7 siblings. All of these 7 siblings exhibited rolandic discharges (RD) on EEG. These observations strongly suggested a genetic link between BECCT and FC. PMID- 1443402 TI - Electrophysiological study of four patients with Fisher syndrome: a mechanism of areflexia. AB - Electrophysiological studies were performed on four patients with the Fisher syndrome (two 4-year-old boys, a 5-year-old boy and a 9-year-old girl). Motor nerve conduction velocity (MNCV), nerve action potential, F wave, H reflex and T reflex were measured at the stage when areflexia was present but ataxia and ophthalmoplegia had recovered. MNCV and SNCV by compound mixed nerve potential were normal in all our patients. The amplitude of the muscle responses (M responses) and compound mixed nerve action potentials were also within normal limits. The latencies of the F waves and F wave conduction velocities were normal. However, H-reflexes and T-reflexes were absent in all four cases. Our results suggested that areflexia in the Fisher syndrome is attributed to the desynchronization of the impulses or the partial conduction block of GIa fibers. PMID- 1443403 TI - Visuo-perceptual impairment and cerebral lesions in spastic diplegia with preterm birth. AB - Eighteen cases of spastic diplegia (SD) ranging in age from 5 year 4 month to 9 year 5 month with preterm birth were studied to clarify the relationship between visuo-perceptual impairment and their cerebral lesions. All underwent neuropsychological examinations including the Frostig developmental test of visual perception, Tanaka-Binet or Suzuki-Binet intelligence test, and MRI examination. Cerebral lesions were detected in all subjects, and the volume of the peritrigonal white matter of the parietal and occipital lobes was significantly correlated with the visuo-perceptual impairment (r = 0.74, in the axial plane; r = 0.64, in the coronal plane). We propose that visuo-perceptual impairment is caused by cerebral lesions and that the measurement of peritrigonal white matter by MRI is useful for detecting potential visuo-perceptual impairment at an early age. PMID- 1443404 TI - Tuberous sclerosis and Down syndrome: a casual association? AB - This paper reports on the clinical, neurophysiological and neuroradiological characteristics of a patient with Down syndrome unusually associated with tuberous sclerosis. In particular, epilepsy is investigated in detail and its polygraphic study and etiopathological factors are discussed. The most interesting findings are those related to the presence of a structural abnormality of the rolandic-parietal cortex, bilaterally, in the form of pachygyria. PMID- 1443405 TI - Vascular dysplasia in Down syndrome: a possible relationship to moyamoya disease. AB - The brain of a child with Down syndrome (DS) and vascular abnormalities is described. Neuropathological examination showed a large cerebral infarction. In the circle of Willis there was hypoplasia of the left middle and posterior communicating cerebral arteries, and microscopically there was thickening of intima and focal disruption of internal elastica in some areas of the circle of Willis. Several reports suggest that the incidence of moyamoya disease is higher in children with DS than in other children. The high incidence of congenital heart disease in DS suggests an abnormality of vascular development that may manifest intracranially as a structural vascular defect, creating a vulnerability to unknown factors important in the pathogenesis of the moyamoya abnormality. PMID- 1443406 TI - Spontaneous occlusion of the circle of Willis (cerebrovascular moyamoya disease): with special reference to its clinicopathological identity. PMID- 1443407 TI - Spontaneous occlusion of the circle of Willis (cerebrovascular moyamoya disease): with special reference to its disease entity and etiological controversy. PMID- 1443408 TI - Moyamoya disease (syndrome) and the Down syndrome. PMID- 1443409 TI - Ring 14 chromosome with complex partial seizures: a case report. AB - A two-year-old girl was found to have a ring 14 chromosome: [46, XX, r(14) (P13 q32.3)]. Her development, including verbal ability, was retarded, her CT scan displayed a low density area anterior to the left temporal lobe, and she suffered from complex partial seizures. Focal central nervous system abnormalities may be present in patients with ring 14 chromosome, and their seizures are not exclusively of the primary generalized type. This is the first case with ring 14 chromosome and complex partial seizures. PMID- 1443410 TI - Cortical reflex myoclonus associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS): a case report. AB - A 9-year-old female MELAS patient with myoclonus is reported, with emphasis on the results of electrophysiological studies of the myoclonus. At age 5 years she experienced a stroke-like episode, and a diagnosis of MELAS was made at age 6 years on the basis of muscle biopsy findings. At age 9 years spontaneous and segmental myoclonus, predominantly affecting the upper extremities, developed because of complications. Electrophysiological examination, including of somatosensory-evoked potentials (SEPs) and averaged EMG for long loop reflexes, revealed so-called "giant SEP" and enhanced long loop reflexes reflecting cortical hyperexicitability. Jerk-locked averaging yielded no myoclonus related spikes, but myoclonus-contingent 4-5 Hz theta bursts appeared. These findings suggest that some types of MELAS may be associated with cortical types of myoclonus. PMID- 1443411 TI - Cerebral aneurysms in children. AB - Childhood intracranial saccular aneurysms are rare, accounting for only 0.6-4.6% of all aneurysms. This paper presents two such cases. A 12-year-old boy developed sudden severe headaches. CT indicated subarachnoid hemorrhage in the bilateral sylvian fissure. Angiography failed to demonstrate any vascular lesions. Repeat angiography, however, revealed a 2 mm aneurysm on the right A-1. A miniclip was successfully applied to obliterate the aneurysm. The postoperative course was uneventful. In the second case, a 3-year-old boy, CT incidentally revealed a bullet-shaped high density area. Angiography demonstrated a large aneurysm arising from the insular portion of the prefrontal branch of middle cerebral artery. This large aneurysm with a broad-based neck was successfully clipped, employing the angioplastic and/or tandem clipping, despite the fact the prefrontal artery unfortunately was compromised in postoperative angiography. The patient was doing well postoperatively. Spontaneous subarachnoid hemorrhage (SAH) in childhood is uncommon. However, when children with SAH is encountered, angiography should be performed repeatedly even if the first angiogram does not demonstrate any vascular abnormality. Childhood aneurysms are increasingly being found incidentally in CT scans. The differences between child and adult aneurysms in regard to site, size, sex predominance, clinical features, and surgical outcome are discussed. PMID- 1443412 TI - A case of Hallervorden-Spatz disease: progressive and intractable dystonia controlled by bilateral thalamotomy. AB - We present a 10-year-old girl with Hallervorden-Spatz disease diagnosed clinically from the neurological manifestations and the characteristic MRI findings. Her main symptom, dystonia, was progressive and resistant to medication, but this dystonia was controlled by bilateral thalamotomy. No clinical progression of the symptoms was recognized at 21 months from the last operation. PMID- 1443413 TI - A search for X-chromosome uniparental disomy and DNA rearrangements in the Rett syndrome. AB - The cause of the Rett syndrome remains unknown but is thought to be related to X chromosome abnormalities. Restriction fragment length polymorphism analysis was employed to search for X-chromosome DNA rearrangements and uniparental disomy in 16 probands and their families. Eighteen different probes, each specific for an area on either the long or the short arm of the X-chromosome, were used. DNA rearrangements were not detected at any of the tested loci. In addition, at each informative locus evidence of both maternal and paternal contributions was found in all probands. Thus, no evidence of either chromosomal abnormality or uniparental disomy was found in the population studied. If uniparental disomy is indeed a causative genetic mechanism for the Rett syndrome, its occurrence may only be infrequent. PMID- 1443414 TI - An answer to F. Andermann's letter about our case report: bilateral porencephalic defect in a newborn after injection of benzol during pregnancy. PMID- 1443415 TI - Fetal alcohol syndrome: a case report of neuropsychological, MRI and EEG assessment of two children. AB - Neuropsychological, neuroanatomical, and electrophysiological data are presented on two subjects with fetal alcohol syndrome (FAS). Both boys had intelligence quotients in the mentally deficient range and were found to have several other severe, specific deficits. Magnetic resonance imaging showed abnormalities of the corpus callosum, and reductions in the size of the basal ganglia and thalamic structures. No focal abnormalities were noted in the electroencephalogram records, although the electroencephalograms of both boys were moderately abnormal for their age group. A multidisciplinary approach to the study of FAS, hopefully will lead to a more unified concept of the disorder and perhaps indicate specific areas of vulnerability. PMID- 1443416 TI - Review of the safety of disulfiram among dually diagnosed patients by Larson et al. PMID- 1443417 TI - Chronic ethanol treatment induces H2O2 production selectively in pericentral regions of the liver lobule. AB - Chronic treatment with ethanol damages pericentral regions of the liver selectively, and reactive oxygen species such as H2O2 may be involved in the mechanism of hepatotoxicity. To test this idea, the effect of chronic treatment with ethanol on rates of H2O2 production was measured in tissue cylinders isolated from periportal and pericentral regions of livers from ethanol-treated rats. Rates of hydrogen peroxide production, assessed from the oxidation of methanol to formaldehyde by catalase-H2O2, were similar in tissue cylinders isolated from periportal regions in control and ethanol-treated rats. In contrast, rates of H2O2 production were over 4-fold higher in tissue isolated from pericentral regions of livers from ethanol-treated than control animals (1.7 +/- 0.5 vs. 0.4 +/- 0.3 nmol/min/mg protein, respectively). Rates of H2O2 generating acyl CoA oxidase activity were equivalent in tissue cylinders from periportal regions of livers from both groups (approximately 2 nmol/min/mg protein), but were over 2-fold higher in tissue cylinders from pericentral regions of livers from ethanol-treated rats than from controls. In contrast, catalase activity was increased nearly 2-fold in homogenates from both periportal and pericentral regions by ethanol treatment while glutathione peroxidase activity was decreased significantly in both regions. These data demonstrate that ethanol increases H2O2 generation in pericentral regions of the liver lobule in part by elevating rates of peroxisomal beta-oxidation of acyl CoA compounds and are consistent with the hypothesis that local increases in H2O2 production may be involved in the mechanism of ethanol-induced hepatotoxicity. PMID- 1443418 TI - Isolation and identification of phytoestrogens from beer. AB - Two estrogenic substances of plant origin have been identified in beer using gas chromatography/mass spectrometry. These phytoestrogens, daidzein and genistein, have previously been shown to be biologically active in animals. Confirming the presence of biologically active phytoestrogens in beer and their possible presence in other beverages, suggests that there may be clinically significant effects related to sustained exposure to phytoestrogens contained in alcoholic beverages. PMID- 1443419 TI - Modification of resistance to Streptococcus pneumoniae by dietary ethanol, immunization, and murine retroviral infection. AB - Hallmarks of the acquired immune deficiency syndrome (AIDS) are immunologic alterations, frequently associated with opportunistic infections. To study such associations, LP-BM5 murine retrovirus infection was used as a murine model of AIDS. Retrovirally infected and uninfected mice were fed a 5% (v/v) ethanol diet for 55 days and then fed a 7% v/v ethanol diet for the final 7 days to assert the role of ethanol as a cofactor in development of murine AIDS. There was a reduction in polymorphonuclear neutrophils count in ethanol-fed groups. Neutrophils increased in retrovirus-infected groups, except those vaccinated 10 days before challenge with live bacteria. The percentage of splenic lymphocytes in the retrovirus-infected group was reduced in comparison with controls. Survival of the mice challenged intraperitoneally with Streptococcus pneumoniae was increased by vaccination and suppressed by dietary alcohol. Retrovirus infection caused a much faster death rate after bacterial challenge than nonretrovirus infected controls. Vaccination played an important role in delaying the death rate in all treated groups. Transferring spleen cells from healthy, unimmunized mice also enabled the retrovirally infected mice to survive the bacterial infection longer. Enhancement of resistance to S. pneumoniae by vaccination and transfer of immunocompetent cells to mice immunosuppressed by retroviral infection show the potential to use immunomodulation to affect disease resistance in AIDS. PMID- 1443420 TI - Ethanol intake of chickens treated with fenfluramine, fluoxetine, and dietary tryptophan. AB - Male, white leghorn chickens fed a standard diet with or without tryptophan supplementation were treated with single injections of 8 mg/kg fenfluramine in one series of experiments, or 8 mg/kg fluoxetine in another series. The birds had been food- and water-deprived prior to injection. They were offered, following the drug or saline injection, water, a 5% ethanol solution, or an isocaloric sucrose solution (8.75%) for 1 hr. Both fluoxetine and fenfluramine significantly reduced consumption of the ethanol solution, an effect exacerbated by tryptophan supplementation. Water or sucrose solution intake was also significantly reduced, but significantly less so than ethanol after fenfluramine injection. Since the birds drank significantly more of the sucrose solution after saline injection than of water, the consumption decrease caused by fenfluramine resulted, nevertheless, in a higher intake than that of either water or ethanol. Body temperature was decreased by ethanol intake and/or fluoxetine injection. Fenfluramine injection had an opposite, body temperature-increasing effect. It appears that both fenfluramine and fluoxetine decrease ethanol intake in a manner more specific than for water or sucrose, and that this effect is amplified by dietary tryptophan supplementation. PMID- 1443421 TI - Surface exposure of synaptosomal gangliosides from long-sleep and short-sleep mice. AB - A galactose oxidase/NaB[3H]4 technique was used to examine the relative surface exposure of gangliosides from whole brain synaptosomes of long-sleep (LS) and short-sleep (SS) mice. The surface exposure of the monosialoganglioside, GM1, did not differ between the two lines. Surface exposure of the polysialogangliosides GD1a, GD1b, and GT1b, however, was significantly greater in LS synaptosomes than in SS. Hydrolysis of the polysialogangliosides by neuraminidase to the end product, GM1, at early time periods occurred more rapidly in LS than in SS synaptosomes. Upon exposure to either 250 mM or 50 mM ethanol, LS synaptosomal ganglioside surface exposure was decreased, but that of SS was increased. Pairwise comparisons of the individual ganglioside classes indicated that the decrease in LS synaptosomal ganglioside surface exposure was attributable to decreases in the polysialogangliosides, compared with controls. The ethanol induced increase in SS synaptosomal ganglioside surface exposure, however, was mainly due to an increased surface exposure of only GD1a. These results suggest that intrinsic differences in the surface exposure of gangliosides and/or the magnitude and direction of ethanol-induced changes in ganglioside surface distribution may reflect biophysical or modulatory mechanisms by which this class of compounds modifies membrane sensitivity to ethanol. These results suggest that further studies should be performed to determine whether gangliosides are factors in genetically determined sensitivity to ethanol. PMID- 1443423 TI - Highlights of the RSA symposium on enzymes of alcohol metabolism. PMID- 1443422 TI - FTIR evidence for alcohol binding and dehydration in phospholipid and ganglioside micelles. AB - We theorize that intoxicants and modern anesthetics bind at the membrane-water interface and displace (dehydrate) bound water molecules by breaking the hydrogen bonds. We tested this hypothesis by examining the effect of butanol on the binding of water to the polar regions of lipids in reversed micelles. Understanding the mechanisms of intoxication requires studies in physiologically relevant systems such as systems containing sialoglycoconjugates, especially gangliosides, which concentrate in the synapses of neural tissue. Therefore, we compared butanol effects on phospholipid with effects on ganglioside. Hydrogen bond breaking activity of 1-butanol was studied in reversed micelles made of dipalmitoylphosphotidylcholine (DPPC), ganglioside (GM1 and GT1b) or the lipid mixture in a D2O-CCl4 medium. Fourier transform infrared spectroscopy (FTIR) data indicated that 1-butanol binds to DPPC and to gangliosides. Adding GM1 to the DPPC micelles introduces a new binding site for the alcohol. GT1b binds more butanol than GM1, because of more binding sites provided by extra sialic acid moieties. Spectral red shifts indicate that both water and butanol bind to the C = O group of sialic acid. Butanol partially releases the surface-bound water by disrupting hydrogen bonds, as indicated by an appearance of a sharp new free OD stretching band of the released D2O molecules. However, control studies with lipid-free systems in CCl4 revealed that a free OD peak could occur from a deuterium exchange reaction between D2O and 1-butanol(ol-h).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443424 TI - Effect of calcitonin on the alcohol drinking of rats. AB - Previous work has shown that calcitonin inhibits eating by rats and that it affects several neurotransmitter systems suspected to play a role in alcohol consumption. The present study was an initial test of whether calcitonin does affect voluntary alcohol consumption by male Wistar rats with prolonged alcohol experience. Calcitonin (20 IU/kg) or saline was injected subcutaneously on 10 consecutive days when the rats (n = 20) had continual access to 10% (v/v) ethanol solution, and to food and water. Using a cross-over design, the effects of 40 IU/kg calcitonin vs. saline were then examined in a second 10-day treatment period. Similar patterns of effects were obtained with both calcitonin doses, but the patterns differed with alcohol, food, and water intake. Alcohol drinking showed biphasic changes with both doses, producing highly significant Treatment x Day interactions (p < 1E-10 and p = 6E-7): it was significantly reduced on the first day of calcitonin treatment and significantly increased on the last few days. Food intake was reduced on all calcitonin days although most markedly on the first. Water drinking was not altered on the first calcitonin day, but was greatly increased on the second, then gradually returned toward the baseline. In a second experiment, the animals were switched to 1 hr of alcohol access per day, and calcitonin (20 IU/kg) was administered periodically to one group 4 hr before the alcohol access. Alcohol drinking was significantly reduced in all cases when the calcitonin injection was preceded by at least 1 day without calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443425 TI - Evidence for normal feedback inhibition of triiodothyronine on the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in abstinent male alcoholics. AB - Disturbances in the hypothalamic-pituitary-thyroid (HPT) axis have been reported in abstinent, noncirrhotic alcoholics, including a reduction in thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) and reductions in triiodothyronine (T3). Some evidence has suggested that a portion of alcoholics may also exhibit a disturbance in the feedback inhibition of thyroid hormone on TSH release. To evaluate the function of the HPT axis negative feedback system in abstinent, noncirrhotic alcoholic men we compared the TSH response with TRH before and after a standard suppressive dose of T3. Ten alcoholic subjects were studied and compared with four control subjects from a previous study and to literature values. The mean percent reduction in TSH response in the alcoholic subjects of 74 +/- 7% was almost identical to the 71 +/- 9% reduction observed in normal subjects. The present findings indicate that noncirrhotic, abstinent alcoholic men exhibit normal suppression of the TSH response to TRH following T3. PMID- 1443426 TI - The effects of maternal ethanol consumption on lactational transfer of immunity to Trichinella spiralis in rats. AB - Transient immunity to the intestinal parasite Trichinella spiralis can be transferred from the mother to the neonate during lactation. The goal of this study was to determine whether maternal ingestion of ethanol during pregnancy and lactation inhibited expression of anti- T. spiralis immunity in nursing pups. Groups of female rats were infected with 1000 T. spiralis L1 larva, mated, and fed either ethanol-containing or isocaloric liquid diets and maintained on diets through pregnancy and lactation or were fed the liquid diets for 30 days before T. spiralis infection, mated, and maintained on diets through pregnancy and lactation. Pups were challenged orally with 200 T. spiralis larva at 14 days postdelivery (preweaning period) or 21 days postdelivery (postweaning period) and were sacrificed either 3 or 8 days after respective challenge. Intestinal worm counts and serum titers of anti-T. spiralis IgG antibodies were determined for each pup. No difference in the number of intestinal worms between pups of ethanol treated and pair-fed dams that received ethanol diet after T. spiralis infection was observed in the preweaning period. This was also true of pups from the dams sacrificed at 3 days after challenge in the postweaning period. However, similar pups sacrificed at 8 days after challenge showed significantly higher worm counts (decreased immunity) relative to their pair-fed controls. Pups of dams that received ethanol containing diet 30 days prior to T. spiralis-infection showed significantly higher numbers of intestinal worms relative to pair-fed pups at both the preweaning and postweaning periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443427 TI - Lactation and prolactin release in foster dams suckling prenatally ethanol exposed pups. AB - The effect of prenatal ethanol exposure on lactation was studied employing prenatally ethanol-exposed pups transferred to foster dams following parturition. During pregnancy, from day 8 to term, dams consumed either standard laboratory chow (ad libitum control), or liquid diets containing 0%, 17.5%, or 35% ethanol derived calories (EDC). To equalize caloric intake, the 0% and 17.5% EDC groups were pair-fed to rats in 35% EDC group. Following delivery, pups born to dams fed with laboratory chow (control) or liquid diets containing 0, 17.5, or 35% EDC were adjusted to eight per litter and transferred to foster dams, which had been fed laboratory chow and water ad libitum throughout pregnancy. Foster dams were implanted with an atrial catheter on day 3 of lactation. On days 6 (early lactation) and 10 (midlactation), following separation of litters from dams for a 6-hr period, a baseline blood sample was removed via a catheter extension. Pups were weighed and returned to the dams. Subsequent blood samples were obtained 10, 30, 60, 120, and 180 min after initiation of suckling. Suckling latency and the amount of milk consumed during the 3-hr suckling were also determined. Litters were weighed on days 2, 6, 10, and 21. The prolactin surge in foster dams in response to suckling by prenatally ethanol-exposed pups was not altered on day 6 of lactation. On day 10, after the initial rise, suckling-induced prolactin was amplified in dams suckled by prenatally ethanol-exposed pups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443428 TI - Chronic ethanol and cocaine-induced hepatotoxicity: effects of vitamin E supplementation. AB - The mechanisms of chronic cocaine toxicity and its potentiation by ethanol were investigated. Cocaine was administered to male C57BL/6 mice (20 mg/kg by peritoneal injection twice a day) alone or in combination with ethanol-containing diets (26% of total calories) supplied with a normal (20 IU/liter) or high content (170 IU/liter) of vitamin E. Liver levels of vitamin E, reduced glutathione, ascorbic acid, and hydroxyproline were measured. Accumulation of thiobarbituric acid-reactive substances, after in vitro stimulation of lipid peroxidation by Fe3+/ADP/ascorbate system, was measured as an index of susceptibility of hepatic membranes to oxidative stress. Plasma alanine aminotransferase, lethality, liver weight, and liver/body weight ratio were determined to assess the extent of liver toxicity. Consumption of ethanol exacerbated liver toxicity induced by cocaine treatments and reduced survival, but ethanol or cocaine treatments alone caused no or only modest mortality. Ethanol potentiated cocaine-induced accumulation of collagen in the liver and depletion of ascorbic acid. Hepatotoxicity induced by the combined ethanol plus cocaine treatment was not accompanied by a decrease in intracellular vitamin E or glutathione content. There were no changes in the basic levels and in the rate of accumulation of thiobarbituric acid-reactive substances in liver homogenates under the lipid peroxidation-stimulating system in vitro. The toxic effects of ethanol and cocaine were not reduced by the ingestion of vitamin E during short term exposure of 21 days of treatment. PMID- 1443429 TI - Enzymatic production of acetaldehyde from ethanol in rat brain tissue. AB - The capacity for the brain to produce acetaldehyde (AcHO) from ethanol was determined in rat brain homogenates. Rat brains were perfused with saline-heparin solution and homogenized in a phosphate buffer. Varying amounts of tissue were incubated with ethanol (0-100 mM) for periods of up to 60 min. The reaction was stopped by the addition of desferrioxamine and ice-cold perchloric acid. Supernatants were treated with dinitrophenylhydrazine reagent, extracted with isooctane in the presence of an internal standard, and the derivatives were separated by HPLC. The addition of 4-methyl pyrazole (an alcohol dehydrogenase inhibitor) or metyrapone (a cytochrome P450 inhibitor) had no effect on the amount of recovered AcHO. On the other hand, treatment with the catalase inhibitors sodium azide, cyanamide, or 3-amino-1,2,4-triazole blocked the production of AcHO while the addition of exogenous peroxide or a peroxide generating system enhanced the production of AcHO. Overall, these results suggest that AcHO may be produced in the brain during alcohol intoxication, through the action of the enzyme catalase. PMID- 1443430 TI - Differences in hepatic microsomal cytochrome P-450 isoenzyme induction by pyrazole, chronic ethanol, 3-methylcholanthrene, and phenobarbital in high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats. AB - High and low alcohol sensitivity (HAS and LAS) rats have been selected for their differences in ethanol-induced sleep time. Liver monooxygenase activities were studied in HAS and LAS rats before and after treatments with known inducers such as chronic ethanol, pyrazole, 3-methylcholanthrene (3-MC) and phenobarbital (PB) to determine whether the selection procedure also selected for differences in the cytochrome P-450 (P-450) inducibility. This previously has been shown with long sleep (LS) and short sleep (SS) mice, which were selected using a similar criterion. 3-MC and PB, in conjunction with chronic ethanol treatment, were used in order to evaluate the interactions of ethanol with these inducers. Prior to treatment, total P-450 content was slightly lower in LAS than in HAS rats. However, both lines displayed the same microsomal monooxygenase activities related to different P-450 isozymes. This was demonstrated by ethoxyresorufin deethylation (EROD) for cytochrome P-450 1A1 (CYP1A1), acetanilide hydroxylation (ACET) for CYP1A2, pentoxyresorufin dealkylation (PROD) for CYP2B, 1-butanol oxidation (BUTAN) and N-nitrosodimethylamine demethylation (NDMA) for CYP2E1. After the different treatments, HAS rats did not differ from LAS rats in their CYP2E1 inducibility. However, pyrazole, PB and 3-MC treatment led to differences in CYP1A and CYP2B monooxygenase activities between the two lines. The enhancement of PROD by pyrazole treatment was less prominent in LAS (1.7-fold of the control value) than in HAS rats (3.8-fold).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443431 TI - A gastric alcohol dehydrogenase in the baboon: purification and properties of a 'high-Km' enzyme, consistent with a role in 'first pass' alcohol metabolism. AB - The major isozyme of alcohol dehydrogenase in baboon stomach, ADH3, has been purified to homogeneity and characterized with a range of alcohol and aldehyde substrates. Using kcat/Km values as an indication of substrate efficacy, medium chain length aliphatic alcohols and aldehydes were identified as the preferred substrates. ADH3 showed 'high-Km' properties with respect to ethanol, and is expected to significantly contribute to 'first-pass' metabolism of alcohol. The enzyme exhibited more than two orders of magnitude higher turnover of substrate than the baboon liver 'low-Km' ADH, and may play a role in the rapid metabolism of a wide range of ingested alcohols in the diet. PMID- 1443432 TI - Alcohol-induced inhibition of LH secretion in intact and gonadectomized male and female rats: possible mechanisms. AB - Alcohol (EtOH) is reported to decrease gonadotropin secretion, but the mechanisms mediating these changes are not fully understood. The present study examined the ability of acutely or chronically administered EtOH to alter plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in both male and female rats, and correlated these changes with blood EtOH levels (BALs); investigated possible changes in the pituitary responsiveness of animals exposed to EtOH; and probed the role of the paraventricular nucleus (PVN) of the hypothalamus in mediating alcohol-induced decreases in plasma LH levels. The injection of 0.5 g EtOH/kg was accompanied by significantly higher BALs in females compared with males. This dose of alcohol did not alter rectal temperature, and only significantly (p < or = 0.01) decreased plasma LH levels in female rats. These findings were not altered by removal of gonadal steroids. Administration of 2.0 g EtOH/kg was followed by BALs that were comparable in both groups of rats at the 1- and 2-hr time-points, but were significantly (p < or = 0.01) higher in females 3 hr after treatment. Rectal T measurably decreased in all rats injected with 2 g EtOH/kg, though intact females showed the greatest change. This alcohol treatment also significantly (p < or = 0.01) inhibited immunoreactive LH release in both sexes, but there were no measurable changes in FSH values at any time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443433 TI - Chronic ethanol consumption induces accumulation of proteins in the liver Golgi apparatus and decreases galactosyltransferase activity. AB - The effect of chronic ethanol consumption on labeled glycoprotein secretion and galactosyltransferase activity has been analyzed in cis- and trans-Golgi apparatus fractions isolated from rat liver. Rats were injected intraperitoneally with 3H-leucine, after different chase periods (30, 60, 180 min), and the radioactivity of the different subcellular fractions as well as of the isolated Golgi apparatus was measured. Chronic alcohol treatment induces an increase in liver weight as well as an enhancement of total liver protein. Ethanol treatment produces a significant accumulation of labeled proteins in isolated Golgi apparatus fractions after a 60- and 180-min chase. An accumulation of labeled proteins in the cytosolic fraction was observed only after 180 min. The alcohol treatment also induces a significant decrease in the activity of galactosyltransferase in both liver homogenate and Golgi apparatus fractions. These results suggest that an impairment of Golgi apparatus functions, including glycosylation and glycoprotein trafficking, could be one of the mechanisms involved in the accumulation of hepatic protein and thus in the pathogenesis of alcohol-induced injury in the liver of chronic ethanol-consuming animals. PMID- 1443434 TI - Outcome in subjects with alcohol-provoked seizures. AB - The outcome in 165 subjects with either an unknown (n = 93) or an alcohol-related (n = 72) seizure etiology, admitted to the emergency room of a general hospital in 1977-1978, was assessed after 10 years on the basis of subsequent hospital records and death-certificate-based mortality data. Alcohol and/or drug poisoning was the most frequent cause of death in the group with alcohol-related seizures. Sixty-four percent of the deaths in this group were directly related to alcohol abuse. The crude mortality was 45.8 (expected 8.6)/100 persons/10 years in the group with alcohol-related seizures and 15.1 (expected 6.0)/100 persons/10 years in the other group, the odds ratio between the groups being 4.8. Twenty percent of those with an unknown seizure etiology were found to show alcohol-related seizures, while the seizure etiology remained unknown in 59%, and a specific etiology other than alcohol abuse was revealed in 21% during the follow-up period. We conclude that alcohol abuse is an important, though often undetected, seizure etiology carrying a poor prognosis. The difference in mortality between the groups was due more to alcoholism than to seizures. There was no difference in mortality between those with a first alcohol-related seizure and those with previous alcohol-related seizures. PMID- 1443435 TI - The Alcohol Clinical Index in lower socioeconomic alcohol-dependent men. AB - The Alcohol Clinical Index, consisting of a 17-item Clinical Signs checklist and a 13-item Medical History questionnaire, was designed to provide an economic screening instrument for alcoholism not subject to self-report biases. There has been little validation work with this instrument. We therefore administered the Alcohol Clinical Index to a group of 40 alcohol-dependent men undergoing treatment at a VA Medical Center and a group of 17 nonalcoholic men being treated at an outpatient medical clinic at the same facility. The Clinical Signs checklist had high sensitivity, but poor specificity. Overall accuracy was 70% for a threshold score from 1 to 5. The Medical History questionnaire had more moderate sensitivity, but 100% specificity for a cutoff score of 2 or more. At a cutoff of 2, it had an overall accuracy of 84%. The high specificity of the Medical History questionnaire suggests that it could be used to help discriminate between alcoholics and nonalcoholics. Further study of these measures and individual items within the measures is recommended with different groups of alcohol users and nonusers. PMID- 1443436 TI - Dose-ranging study of depot disulfiram in alcohol abusers. AB - The object of this early Phase 2 study was to determine the dosage of depot disulfiram (DSF) required to induce sustained sensitivity to alcohol. Sixteen abstinent alcohol abusers were studied in an unblinded ascending-dose trial of DSF suspended in either (1) 5% methylcellulose or (2) 0.1% polysorbate 80. Five pairs of subjects received a single subcutaneous dose of Formulation A (1.0, 2.0, 2.5, 3.0, or 3.5 g). Three pairs were treated with Formulation B (60, 75, or 90 mg/kg) plus an oral loading dose of DSF (15 mg/kg). Subjects were challenged with oral alcohol (0.15 g/kg) before treatment, and on days 7, 14, 21, and 28. Subjective and objective responses to alcohol challenges (skin temperature, breath acetaldehyde, pulse rate, and blood pressure) were measured, and mobilization of DSF was assessed by carbon disulfide levels in breath. Treatment with Formulation B (75 or 90 mg/kg) plus an oral-loading dose (15 mg/kg) was consistently followed by sustained sensitivity to alcohol. Some subjects experienced the subjective and objective features of the DSF-ethanol reaction for 28 days, but these reactions achieved statistical significance only on day 7 for objective changes and on days 7 and 14 for subjective discomfort. Breath carbon disulfide was detectable until day 28 in all subjects receiving more than 1.0 g DSF, demonstrating sustained release of the drug. Treatment with depot DSF merits further study for its potential benefits in chronic alcohol abuse. PMID- 1443437 TI - Ascites as a marker for the hyperdynamic heart of Laennec's cirrhosis. AB - The purpose of this study was to determine the relation of the circulatory findings of cirrhosis to hepatic decompensation. Twenty individuals with biopsy proven cirrhosis and 15 aged-matched controls underwent echocardiographic evaluation of cardiac function. Cardiac dimensions and indices derived from echocardiograms were related to various measures of liver decompensation. Cirrhotics had a higher heart rate, left ventricular end-diastolic volume, left ventricular ejection fraction, and cardiac output and a lower mean blood pressure and peripheral resistance than aged-matched subjects. On multiple regression analyses mean blood pressure, peripheral resistance, and cardiac output were all found to be related to estimates of ascites. Also, cirrhotics with ascites had a lower peripheral resistance than those without this finding. CONCLUSION: In clinically stable patients with cirrhosis, the presence of ascites indicates an intense vasodilatory state with a hyperdynamic circulation. PMID- 1443438 TI - Relationship of insulin resistance to protein-energy malnutrition in patients with alcoholic liver cirrhosis: effect of short-term nutritional support. AB - Protein-energy malnutrition (PEM) and insulin resistance (IR) are common features of alcoholic liver cirrhosis (ALC). In order to determine a relationship between them, nutritional status and glucose homeostasis were studied in 26 patients with ALC. Nutritional status was assessed through dietary, anthropometric, and biological parameters. An IR index (M/I) was obtained from the euglycemic insulin clamp technique. M/I was significantly correlated with accurate markers of PEM (albumin, transthyretin, and retinol-binding protein) but not with other markers of liver dysfunction. Nine patients were studied before and after nutritional support: M/I was significantly improved as were serum markers of PEM. Other markers of liver dysfunction were also significantly improved. These findings suggest that PEM could be responsible, in part, for IR in patients with ALC who are frequently malnourished. Moreover, nutritional support improved insulin sensitivity in these patients. PMID- 1443439 TI - Brain morphologic characteristics of cirrhotic alcoholics and cirrhotic nonalcoholics: an MRI study. AB - Cirrhotic alcoholics, cirrhotic nonalcoholics, and normal controls were compared on planimetric and subjective ratings of the MRI of the brain. The results indicated that the cirrhotic alcoholics exhibited more gross pathology than the nonalcoholic cirrhotics on ratings of frontal, parietal, and cerebellar atrophy; however, these groups were more similar to each other than they were different on planimetric measurements. The results are discussed in terms of the etiology and localization of the neuropathologic sequelae found commonly among alcoholics. PMID- 1443440 TI - Oral magnesium supplementation improves metabolic variables and muscle strength in alcoholics. AB - Magnesium deficiency is common among chronic alcoholics, but the knowledge of oral magnesium supplementation to this group is limited. We, therefore, randomized 49 chronic alcoholics, moderate to heavy drinkers for at least 10 years to receive oral magnesium or placebo treatment for 6 weeks according to a double-blind protocol. Effects on metabolic variables and muscle strength were analyzed. Significant reduction of aspartate-aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen after magnesium, whereas no change was observed with placebo. Bilirubin decreased in both groups. Serum Na, Ca, and P increased significantly during magnesium therapy compared with no statistically significant change in the placebo group. Serum K and Mg increased slightly after magnesium supplementation and decreased in the placebo group, resulting in a significant difference between the two groups at the end of the study. Muscle strength increased significantly during magnesium treatment, contrasting to no change with placebo. Blood pressure, heart rate, hematological variables, serum lipids (cholesterol, HDL, TG), glucose tolerance, and creatinine were unchanged in the two groups after treatment. Alcohol consumption was similar before and during the trial and does not explain the differences between the two groups The results shows that short-term oral magnesium therapy may improve liver cell function, electrolyte status, and muscle strength in chronic alcoholics. PMID- 1443441 TI - Subjective feelings of alcohol intoxication in Asians with genetic variations of ALDH2 alleles. AB - Asian-American men who possess ALDH2*2 alleles and who experience a facial flush after consuming alcohol were carefully matched on drinking history and demographic variables with nonflushing Asian males with only ALDH2*1 alleles. Each man was tested following placebo and a challenge dose of 0.75 ml/kg alcohol. Following alcohol, flushers reported experiencing significantly more positive feelings of intoxication than nonflushers, despite equivalent blood alcohol concentrations. These data suggest that Asians who flush after drinking, particularly those with ALDH2*1/2*2 genotype, have a more intense, although not necessarily a more negative, response to alcohol than comparable nonflushing Asians. This alcohol sensitivity reaction that many Asian flushers experience may contribute to their lower tendency to drink excessively, even though their response to alcohol is not predominantly negative. PMID- 1443442 TI - The short-term psychological health of alcoholic and non-alcoholic liver transplant recipients. AB - In response to limited resources and overwhelming clinical need, we previously developed an approach to alcoholic patient selection for liver transplant based on factors reported to predict short- and long-term sobriety in prospective studies of alcoholics. The present study reports follow-up data comparing alcohol dependent (n = 22, DSM-3-R criteria) and non-dependent (n = 39) subjects followed from 6 months to 3 years post-transplant. Nine percent of the alcoholics had returned to symptomatic drinking with 14% reporting some exposure to ethyl alcohol. Nearly half (46%) of the non-alcoholic group reported occasional social alcohol use. The alcoholic patients were less likely to be in their first marriage and more likely to be asked about alcohol use at follow-up clinic visits. In most other respects the two groups resembled each other more often than they differed. The alcoholic group reported continued high rates of prognostic factors associated with long-term abstinence although the content of these shifted noticeably between pre- and postoperative assessment. Members of both groups reported high frequencies of medication side effects, of missed doses of medications, and of depressive symptoms. Most felt the transplant had improved their lives but had brought on significant financial burden. There were no differences in subjective appraisals of either psychological or physical health between the two groups. These follow-up data suggest that carefully selected alcohol dependent patients will do as well as non-dependent patients after liver transplant. PMID- 1443443 TI - Atopic eczema: role of microorganisms on the skin surface. AB - The pathophysiology of atopic eczema (AE) is still poorly understood. One possible concept favors IgE-mediated reactivity towards allergens that enter the skin from the outside or through the blood. Microorganisms of the cutaneous flora also might represent a stimulus for allergic skin reactions. Abnormal bacterial skin colonization is a characteristic feature of AE. Staphylococcus aureus (S. aureus) is the most common pathogen. Binding to host cells involves special receptors, such as fibronectin or laminin. Specific IgE antibodies to S. aureus can be detected in the blood. Whereas the clinical relevance of anti staphylococcal antibodies is still controversial, specific IgE antibodies to Pityrosporum species as well as positive type I prick test reactions to these yeasts seem to correlate with the intensity of eczematous lesions in the head and neck regions of patients with AE. Both antimicrobial and antifungal treatment has been shown helpful in some cases of AE. PMID- 1443444 TI - T-cell receptor V elements regulate murine IgE production and airways responsiveness. PMID- 1443445 TI - Serum IgE levels and allergic spectra in immigrants to Sweden. AB - We evaluated the allergy status of 134 immigrants from Asia, Africa, the Middle East and South America, who were referred to our clinic during the past 10 years. Fifty Swedish patients were used for comparison. When the atopy state was not taken into account, no significant difference was found between the two groups with respect to total IgE levels. However, IgE levels of non-atopic immigrants were significantly higher than the IgE levels of non-atopic Swedes. While there was no significant difference in IgE levels between atopic and non-atopic immigrants, this difference was significant in Swedish patients. In general, IgE levels of immigrants showed a decline with time and reached approximately the same levels as for the Swedish patients in 10.5 years. In the immigrant group atopic women had a considerably lower IgE level than the atopic men. Among the atopics there were no differences between sexes. In Swedes and immigrants pollen was the most common group of allergens. The spectrum of allergy in the immigrant group changed with time in Sweden, and gradually became more similar to the Swedish spectrum. Skin and/or RAST positivity to birch increased from 16% within 2.5 years to 53% after more than 10.5 years in Sweden. Our data indicate that environmental factors rather than hereditary differences determine the IgE state. Within a few years the immunologic status of immigrants adapts to the new environment. PMID- 1443446 TI - Clinical and immunological effects of immunotherapy with alum-absorbed grass allergoid in grass-pollen-induced hay fever. AB - A double-blind, placebo-controlled study of immunotherapy was conducted in 19 patients with grass-pollen hay fever to evaluate the efficacy and safety of a formalinized depot grass allergoid. The patients were assessed before and during IT by clinical (symptom-medication scores during the grass- pollen season, specific nasal and skin reactivity) and immunological (specific IgE, IgG, IgG1 and IgG4 antibodies) parameters. High doses of grass allergoid, corresponding to a cumulative pre-seasonal dosage of 46,050 PNU, were administered, with only one systemic reaction. The actively treated patients had significantly lower symptom medication scores than placebo (p less than 0.01) during the month of May and showed a significant decrease in specific skin (p less than 0.01) and nasal (p less than 0.05) reactivity, and a significant early increase in specific IgE (p less than 0.01), IgG (p less than 0.0005), IgG1 (p less than 0.001) and IgG4 (p less than 0.05), with a subsequent decrease of IgE and IgG1. No differences were detected in any of these parameters in the placebo group. A correlation was found between high IgG4/IgG1 ratio and the specific skin reactivity decrease (r = 0.691, p less than 0.05), whereas a high IgG4/IgG1 ratio was associated with higher symptom-medication scores (r = 0.654, p less than 0.05). Possible explanations of these apparent discrepancies are proposed. PMID- 1443447 TI - Is atopy a risk factor for the use of contact lenses? AB - We studied the tolerance of soft contact lenses (CL) in 24 atopic (16 with hay fever) and 52 non-atopic subjects with a mean age of 20 years. They were examined when they first came to an ophthalmologist to have CL and re-examined after an average of 1.7 years. All subjects were allowed to use CL throughout the year, including the pollen season. Of the 76 subjects, 31 (41%) reported some kind of eye symptoms during the use of CL. Six subjects (8%) had stopped using CL because of symptoms. Altogether, in 29/76 subjects (38%) some objective sign was detected in the examination, confirming the subjective symptoms (conjunctivitis 16, keratoconjunctivitis 8, increased limbal blood vessels 4, and eczema palpebrae 1). Fourteen of the 24 atopics (58%) had experienced symptoms compared with 17 of the 52 non-atopics (33%) (p = 0.034). Eleven atopics had seasonal eye symptoms, and eight of them (73%) had problems with CL use. Eosinophils and neutrophils found in the conjunctival scrapings at the first examination appeared to predict poor CL tolerance when the occurrence of symptoms in different groups was first compared by bivariate analysis. The risk factors that could predict poor CL tolerance were also evaluated, with logistic regression analysis controlling potential confounders. History of an atopic condition increased 5-fold the risk of experiencing various external eye symptoms during the use of CL. We conclude that seasonal atopic allergy is a especially risk factor for wearing soft contact lenses, and their use should be restricted during the season. PMID- 1443448 TI - Specific IgE antibodies to vespids in the course of immunotherapy with Vespula germanica administered to patients sensitized to Polistes dominulus. AB - Sera from a group of 12 patients with anaphylactic reactions to vespids were studied. Field observations and RAST values suggested that the offending insect was Polistes dominulus (PD). Specific IgE antibodies to PD appeared in all cases and to Vespula germanica (VG) in nine. Absorption studies in these basal sera showed that IgE antibodies to VG were due to cross-reactivity with PD. The RAST value to both venoms was higher after immunotherapy (IT) in six cases. IgE antibodies increased to determinants common to both vespids, and in 41% of the cases to specific epitopes of VG venom allergens not initially detected in the basal sera. In one case antibodies increased only to VG without a corresponding rise to PD. These results indicate that if the correct venom to which the individuals are sensitized is not administered IgE antibodies may appear which were not initially detected in the patients' sera. The levels of these antibodies declined during the course of IT. PMID- 1443449 TI - Circulatory basophilia in guinea pigs with delayed-type hypersensitivity. Topical antigenic provocation induces circulatory basophilia. AB - Circulatory basophilia could be induced in inbred guinea pigs systematically immunized with ovalbumin and consequently provoked repeatedly with dissolved ovalbumin applied onto the mucosa of the nares or the outer eye. The degree of the increase in circulatory basophil granulocytes depended on the adjuvant used and was significantly more pronounced after immunization with Freund's complete adjuvant than with alhydrogel (Al(OH)3). The degree of basophilia was also dependent on the animal strain, but different in two strains selected for high asthma trait. PMID- 1443450 TI - Protective effect of different doses of terfenadine on the conjunctival provocation test. AB - The protective effect of terfenadine on inflammatory processes following the early phase of conjunctival provocation tests by specific allergen was assessed in 24 patients suffering from seasonal allergic rhinoconjunctivitis, in a single blind, randomized, placebo-controlled, parallel-group study. Patients were randomly assigned to four treatment groups, each being given terfenadine 60, 120, 180 mg daily, or placebo, respectively, for 7 days, out of the pollen season. Clinical severity (burning, itching, lacrimation and hyperemia), and number of inflammatory cells obtained by conjunctival scraping (neutrophils, eosinophils, lymphocytes, and monocytes) were evaluated before and after treatment. Pre treatment with terfenadine resulted in a significantly higher allergen threshold dose than placebo (p less than 0.01), regardless of drug dose. Patients given terfenadine experienced a significant reduction (p less than 0.03) in conjunctival symptom severity, as compared with placebo, following conjunctival challenge. Accordingly, the number of inflammatory cells in terfenadine-treated patients was significantly lower (p less than 0.01) than in the placebo-treated after the conjunctival provocation test. The results of this study suggest that terfenadine has a significant protective effect on the early-phase cellular and clinical events of conjunctival reaction induced by allergen challenge in atopic patients. PMID- 1443451 TI - A double-blind comparison of nasal budesonide and oral astemizole for the treatment of perennial rhinitis. AB - Sixty-nine outpatients with symptomatic perennial rhinitis were recruited to this double-blind, parallel-group study to compare budesonide nasal spray with oral astemizole. Following a 1-week run-in on placebo, 67 patients achieved a mean daily total symptom score of at least 4 (scoring for each symptom was 0 = none, 1 = mild, 2 = moderate, 3 = severe), and were randomized to study treatments - 33 to budesonide, 100 micrograms in each nostril morning and evening, and 34 to astemizole, one 10-mg tablet each morning, for a period of 4 weeks. No antihistamine preparations other than eye drops and no corticosteroids were permitted during the active treatment period. Patients recorded symptoms of blocked nose, runny nose, sneezing, itchy nose, sore eyes or runny eyes in diary cards each evening before retiring. Diary card data showed that there was significantly greater improvement in blocked nose, runny nose and runny eyes during the first 2 weeks of budesonide treatment than during the same period on astemizole. A similar, although non-significant, trend was observed for sneezing and itchy nose, but there was no apparent difference in the reporting of sore eyes. After 4 weeks, blocked nose and runny nose remained significantly less troublesome in the budesonide group. Both treatments were well-tolerated and no major adverse effects were reported. Patient ratings for treatment efficacy were significantly higher for budesonide than astemizole at both 2 weeks and 4 weeks. PMID- 1443452 TI - Local nasal immunotherapy in allergic rhinitis to Parietaria. A double-blind controlled study. AB - Preseasonal local nasal immunotherapy (LNIT) by means of an extract in macronized powder form has been studied in allergic rhinitis to parietaria. Twenty-four Parietaria-sensitive patients have been studied for 18 weeks in a double-blind controlled trial. Subjects were selected on the basis of a positive skin test, RAST and intranasal challenge to Parietaria antigen. Three eight-patient groups were randomly planned: the first group was given native Parietaria product, the second modified Parietaria product, and the third placebo. During the pollen season no difference was observed in mean weekly symptom score between the three groups, while the mean weekly medication score was significantly lower in the treated groups than the control group. Only the treated groups showed a significant increase in specific nasal threshold to Parietaria after treatment. Adverse reactions to LNIT, limited to the upper respiratory tract, occurred rarely and did not interfere with the dose schedule. This study indicates that LNIT in powder form may be a suitable alternative to the traditional subcutaneous immunotherapy in terms of clinical efficacy and safety. PMID- 1443453 TI - Conjunctival provocation test: high clinical reproducibility but little local temperature change. AB - Ten atopic and five healthy individuals participated in eight conjunctival provocation tests (CPT) in an effort to improve the CPT procedure. Results were evaluated by thermography and the use of conventional criteria under various conditions. Due to considerable spontaneous variability and change in temperature already after instillation of diluent, thermography was not sensitive enough to identify positive CPT results. The precision of the CPT was within one 10-log step in all tests and in all patients. Itching appeared before erythema in 83% of subjects and within 5-8 min after instillation of the allergen. This was true also when only one eye was used for the CPT. We therefore conclude that the CPT procedure can be used in one eye every 5-8 min when indicated in clinical routine and that it is a safe, precise method. PMID- 1443454 TI - Pulmonary tuberculosis in patients treated with inhaled beclomethasone. AB - Inhaled beclomethasone dipropionate (BDP) has been used with few side-effects in the treatment of bronchial asthma for 2 decades. Until now the manifestation of tuberculosis (TB) in patients on inhaled BDP has not been reported. Eight patients with allergic asthma, of a total of 548 asthmatics (1.46%) seen over a 2 year period, developed active TB following the use of inhaled BDP. All were sputum-positive for acid-fast bacilli (AFB) on smear and/or culture, all responded well to a combination of anti-TB drugs, and none showed evidence of immunological or pituitary-adrenal suppression. Two patients agreed to a repeat administration of BDP; both developed TB again within 2 weeks and are again on anti-TB treatment. PMID- 1443455 TI - Early and late-phase asthmatic reactions: a hypothesis. AB - Why might a foreign particle, exercise or fog inhalation precipitate two asthmatic reactions? It is reasonable to suspect that asthmatic patients develop two reactions because healthy subjects may also develop two physiological responses to the same stimuli. This suggestion is supported by the observation that living things have developed adaptative systems to confront either sudden or persistent changes in the environment or within the internal milieu. The results of several studies suggest that the early phase response (EPR) usually involves cells which are normal residents of the respiratory epithelium (mast cells) and pre-formed substances (histamine), whereas cells participating in the late phase reaction (LPR) are recruited from the circulation (eosinophils, basophils and T cells). Up to now most of the studies of the EPR and LPR have been addressed to detecting a cell or metabolite abnormality. This simplistic approach would probably not improve the knowledge of the mechanisms involved in asthmatic responses. Since the presence of isolated or dual responses seems to depend on the intensity and duration of the stimuli it is reasonable to suspect that EPR and LPR are the result of an excessive adaptative response of the bodies of asthmatics to sudden and prolonged/strong stimuli, respectively. PMID- 1443456 TI - Nasal memory T lymphocytes capable of producing IL-4 in the allergic reaction. AB - This paper reports the presence of memory T cells in the nasal mucosa of allergic patients. The demonstration of CD4+/CD29+ (CD4+/CD45RO+) T lymphocytes, which are capable of interleukin-4 production, can indicate a complementary cell-mediated regulatory mechanism for mast cell proliferation and IgE synthesis in human nasal allergy. No substantial IgE production can be obtained in the absence of IL-4. Therefore, the existence of IL-4 producing cells on site in the nasal mucosa of allergic subjects probably implies a complementary interaction between cytokines and different immunocompetent nasal cells in the regulation of B cells and IgE synthesis. PMID- 1443457 TI - Hypersensitivity to trimethoprim. AB - We present two patients who experienced life-threatening immediate reactions and one patient who developed generalized urticaria following oral administration of trimethoprim (TMP) and sulfamethoxazole (SMX) combination. Skin prick tests with TMP were positive in the three patients. No patients reacted to skin prick tests with SMX. No significant levels of IgE antibodies to TMP were found by RAST in the serum of the patients. Normal subjects used as controls did not react to any of these tests. Single-blind, placebo-controlled oral challenges were positive with TMP and negative with SMX in all patients. These results suggest that the three patients developed type I hypersensitivity reactions to TMP. In our patients skin prick tests with TMP were useful in TMP hypersensitivity diagnosis. PMID- 1443458 TI - Recurrent pericarditis: a rare complication of allergen immunotherapy. AB - We report on a 29-year-old woman suffering from hay fever due to grass and olive tree pollens. She developed recurrent pericarditis during her first course of immunotherapy with an alum-adsorbed pollen extract. A causal relationship was established between the allergen injections and the acute pericarditis episodes on two consecutive occasions, which presented with blood eosinophilia. Blood cultures and serological tests for microorganisms were negative. There were no signs of autoimmune disease or systemic vasculitis. To the best of our knowledge, allergen immunotherapy-induced pericarditis has not been previously reported. PMID- 1443459 TI - [Skin melanomas of the head and neck: therapeutic value of cervical lymphatic dissection]. AB - There is a conflicting evidence regarding the value of a regional lymph node dissection in early clinical stages of head and neck Melanomas. The AA. reviewed the clinical histories of 500 patients presenting a malignant melanoma localized in the head and neck region and treated in their Hospital between 1967 and 1987. Results showed that the prophylactic neck dissection is necessary for lesions between 0.75 and 1.5 mm in thickness, whereas in tumours with a depth of invasion greater than 1.5 mm the outcome of the disease is not improved by the prophylactic neck dissection. PMID- 1443460 TI - [Review of ORL manifestations in AIDS. Case series at the Arnau de Vilanova Hospital, Lleida]. AB - The majority of patients suffering AIDS-syndrome present with ENT aspects, being the most prevalent lateral adenopathy of the neck firstly, followed by thrush, pharyngo-esophageal candidiasis and herpes simplex. Differences regarding the distribution in percentage in risk groups are signaled by the AA. between their own statistics and those of the americans writers. PMID- 1443461 TI - [Diagnostic and therapeutic management in malignant neck tumors of unknown origin. Our experience in the last 5 years]. AB - The AA. analyzed 37 cases of metastatic neck cancer from unknown primary sites treated at the Oncologic Unit from 1986 to October 1991. This group account for 7 percent of total cervicofacial tumors seen. Factors that affected survival include the symptoms of consult, the control of cervical disease after treatment and surgery. The survival was 50 percent at two years and the rate of neck disease control amounted to 57.7 percent. PMID- 1443462 TI - [Sarcoidosis as a cause of paralysis of the recurrent laryngeal nerve. Presentation of a case]. AB - A patient with Sarcoidosis presented with hoarseness in the course of the disease, caused by mediastinal adenopathies compressing the left recurrent laryngeal nerve. Vocal cord paralysis is an unusual complication of sarcoidosis. We have found in the consulted worldwide bibliography on the subject only four cases of sarcoidosis with mediastinal enlarged lymph nodes causing compression of the left recurrent nerve and subsequently vocal paralysis. PMID- 1443463 TI - [Iatrogenic foreign body of the esophagus]. AB - The AA. report the case of a 79 years-old patient suffering an esophageal stenosis managed with intubation (Celestin's tube). This instance shows the good tolerance of the prosthesis by the patient as well as the undue of its stay. And by the way, the simplicity of its removal with a rigid esophagoscope, as was the present case. The paper contemplates a brief review of the indications for esophageal intubation and possible complications when dealing with organic stenosis of the esophagus. PMID- 1443464 TI - [Characteristics of subglottic and glottic-subglottic carcinomas]. AB - The 14 subglottic and glottic-subglottic carcinomas treated in the Otolaryngologic Department of the AA. between 1984 and 1989 are reviewed. Check of literature about subglottic carcinomas. PMID- 1443465 TI - [Prognostic value of histopathological parameters in epidermoid carcinoma of the vocal cords in T-1 stage]. AB - In this paper are studied macro- and microscopically, 14 histopathologic parameters belonging to 37 patients suffering from vocal cord squamous cell carcinoma, stage T-la. All patients were submitted to cordectomy and followed up during a 5 years term, as a minimum. A discriminant analysis was performed in order to establish the relation between histopathologic parameters and local failure. Only two of them were statistically significative (p < 0.01): the structural type and the differential degree of tumor cells. The histopathological study allowed the prediction of 82 percent of local recurrences. PMID- 1443466 TI - [Prolactinoma as atypical tumor of the nasopharynx]. AB - The paper deals with a Prolactinoma case appearing as a swelling of the rhinopharynx, which developed cephalgia related to the nasal blockade as solitary symptom. Recite of the main clinical characteristics, diagnostic process and therapeutics of this condition. The differential diagnosis with other tumors situated in the sellar space or in the rhinopharynx, is also considered. PMID- 1443467 TI - [Thyroid gland stimulation test in Reinke's edema. A study of 28 patients]. AB - In order to clarify the correlation between Reinke's oedema and thyreopathies, we performed a study on 28 patients affected by polypoid degeneration of the vocal cords. Every patient had a complete check-up concerning the otorhino laryngological either endocrinological aspects, in particular blood laboratory tests including the routine ones and RIA for T3, T4, FT3, FT4, hGT, antibodies and TSH under stimulation of the TRH. 22 patients showed to be affected by subclinical hypothyroidism; 5 patients did not show a substantial increase of the TSH to the TRH stimulation; one patient was affected by hypothyroidism. Our experience clearly shows that subclinical hypothyroidism is the organic pathology more frequently correlated with Reinke's oedema. PMID- 1443468 TI - [Histiocytoid hemangioma]. AB - Angiolymphoid hyperplasia with eosinophilia is a multisystemic disease characterized mainly by cutaneous nodules, vascular proliferation with atypical histiocytoid endothelial cells and numerous eosinophiles, often with blood eosinophilia. It use to recur "in situ" and persist after surgical excision. The AA. review the literature about this rare tumor and present the clinical and histopathological features of a case of Angiolymphoid hyperplasia with eosinophilia of the tongue. PMID- 1443469 TI - Twin challenges. PMID- 1443470 TI - Does the laryngeal mask airway compromise cricoid pressure? AB - The laryngeal mask airway was inserted in 10 cadavers. At postmortem the chest was opened and an infusion set primed with a dilute barium solution was inserted into the oesophagus and ligated in place. A cricoid force of 43 N was then applied and the infusion set was positioned so that when the clamp was opened it generated a pressure of 7.8 kPa within the oesophagus. The cricoid pressure was able to stop the flow of fluid into the oesophagus. This demonstrates that cricoid pressure is effective in preventing reflux at intragastric pressures which are encountered clinically and the presence of the laryngeal mask airway does not compromise this. PMID- 1443471 TI - Unconscious learning during anaesthesia. AB - Forty-three surgical patients were, during general anaesthesia, presented (via headphones) with either statements about common facts of some years ago (group A), or new verbal associations, i.e. the names of fictitious, nonfamous people (group B). None had any recall of intra-operative events. In a postoperative test of indirect memory, patients in group A answered more questions about the 'common facts' correctly than those in group B (p < 0.005), which reflects the activation of pre-existing knowledge. Furthermore, patients in group B designated more 'nonfamous names' as famous (thus falsely attributing fame) than patients in group A (p < 0.001), which demonstrates that information-processing during anaesthesia can also take place as unconscious learning. PMID- 1443472 TI - The influence of arm position and cardiac output on bolus clearance from the arm. AB - The importance of arm position and cardiac output on the clearance of a bolus injection from the arm was assessed in 63 patients using technetium-99m. Injections were made in the left arm which was either adducted, abducted or adducted with the forearm flexed over the lower chest. The clearance of isotope was assessed by measuring the amount of radioactivity remaining in the arm at 10 s intervals and calculating it as a fraction of the injected dose. The clearance of Tc-99m was significantly faster and more complete from the abducted arm than from the adducted arm. There was no correlation between clearance and cardiac output. PMID- 1443473 TI - Cannulation of the internal jugular vein. The very high approach. AB - A new approach to internal jugular vein catheterisation in the neck (the 'very high' approach) was used in 335 patients over a 12-month period. The success rate was 100% and there were no complications. It proved to be an easy technique to learn and may be particularly useful in difficult and emergency situations. PMID- 1443474 TI - Six months of shivering in a district general hospital. AB - Of 2595 patients admitted to a recovery room in Derbyshire Royal Infirmary over a 6-month period, 164 (6.3%) shivered postoperatively. Data regarding the anaesthetic techniques to which these patients had been subjected were gathered from the Derby Anaesthetic Audit System. Subsequent analysis demonstrated the importance of a number of factors that led to shivering, including male gender, anaesthetic techniques involving spontaneous ventilation, and anticholinergic premedication. The administration of pethidine, alfentanil or morphine intra operatively reduced the incidence of shivering postoperatively. PMID- 1443475 TI - The laryngeal mask airway in infants. AB - Clinical and fibreoptic assessment of positioning of the size 1 laryngeal mask airway was performed in 50 infants. A clinically patent airway was obtained in 47 patients at the first attempt, but perfect positioning, as assessed by fibreoptic laryngoscopy, was found in only 22 instances. Despite an airway initially patent, delayed airway obstruction occurred in 12 infants. It is concluded that clinical airway patency does not guarantee ideal positioning of LMA in infants, and that care should be taken to ensure continued airway patency because of the tendency of the LMA position to deteriorate in this group of children. PMID- 1443476 TI - Profound hypotension following intravenous codeine phosphate. Three case reports and some recommendations. AB - Three adults are described who developed life-threatening hypotension following intravenous codeine phosphate. It is recommended that codeine phosphate should not be given intravenously to adults. PMID- 1443477 TI - Repeated unilateral epidural blockade. AB - Unilateral epidural analgesia occurring in a parturient three times in successive pregnancies is reported. Possible causes are reviewed, and clinical and radiological evidence in support of the most likely explanation are presented. PMID- 1443478 TI - Profound desaturation following vomiting on induction. A case for routine pre oxygenation. AB - Whilst participating in a clinical trial, a patient vomited during induction of anaesthesia. Subsequent analysis of the continuous record of oxygen saturation showed precipitous desaturation. PMID- 1443479 TI - Anaphylactoid reaction to propofol. AB - A case of an anaphylactoid reaction following the induction of anaesthesia is reported. Subsequent intradermal testing suggested propofol to be the causative agent. PMID- 1443480 TI - Anaesthetic machine checking practices. A survey. AB - Forty anaesthetists, of all grades, were interviewed without prior warning and questioned about the checks they had performed on their anaesthetic equipment before use. The results reveal that a substantial percentage (up to 41%) of anaesthetists perform inadequate checks. Furthermore, of those that do, few follow the Association of Anaesthetists of Great Britain and Ireland's recent guidelines. PMID- 1443481 TI - Evaluation of the Level 1 Hotline blood warmer. AB - The Level 1 Hotline warmer is a new type of fluid warmer, developed specifically for use with low flows. It was found to be effective at flows between 1 ml.min-1 and 75 ml.min-1. PMID- 1443482 TI - The extensometer--use in spontaneously ventilating awake volunteers. AB - The extensometer is a new device with potential in the field of respiratory pattern analysis. This paper describes the physical principles upon which the extensometer depends and also assesses its performance as a noninvasive respiratory monitor in respect of its ability to measure tidal volume and to determine obstructive breathing patterns in awake volunteers in the supine position over a limited time period. Further developments of the device are outlined and the current status of torso transducers in anaesthesia and intensive care are discussed. PMID- 1443483 TI - An evaluation of the gum elastic bougie. Intubation times and incidence of sore throat. AB - This study was designed to evaluate the routine use of a gum elastic bougie for tracheal intubation. The median time to intubation with the gum elastic bougie while simulating an 'epiglottis only' view was only 10 s longer than the time taken during conventional intubation with an optimum view. Three of the patients required a gum elastic bougie-assisted intubation after attempts at conventional visual intubation had failed. There was no significant difference in the incidence of postoperative sore throat and hoarseness between the two groups. We recommend that anaesthetists should use the gum elastic bougie whenever a good view of the glottis is not immediately obtained. PMID- 1443484 TI - The Mancunian way. AB - The authors have examined early records of the administration of ether anaesthesia in Manchester and the lives of several medical men involved in these events. Charles Strange, a dentist and chemist, in a letter to the Manchester Guardian published on 14 January 1847, described a self-administration of ether for dental extraction, but George Bowring, a surgeon, subsequently claimed the first anaesthetic administered by a doctor in Manchester. The merits of these claims are discussed in the light of the circumstances surrounding these events. PMID- 1443485 TI - Plasma concentrations of flumazenil during liver transplantation. AB - Six patients were given flumazenil (1 mg) during the anhepatic period of liver transplantation. We found higher mean plasma flumazenil concentrations during the anhepatic period than occurred in patients with hepatic cirrhosis. It was only possible to measure plasma flumazenil concentrations in four patients after revascularisation of the donor liver. Of these, elimination half-lives could be calculated in only three patients (normal in one and prolonged in two). In these two patients the elimination half-lives were prolonged to the same extent as in patients with fulminant hepatic failure. The changes during the anhepatic period occur because the liver contributes to the central volume of distribution. After revascularisation of the donor organ the prolonged half-lives indicate that transplanted livers may not recover normal metabolic functions immediately. PMID- 1443486 TI - Local anaesthetic: does it really reduce the pain of insertion of all sizes of venous cannula? AB - A recent study performed in this department showed that a subcutaneous injection of local anaesthetic was significantly less painful than the insertion of a 22 gauge venous cannula. However, our colleagues remained sceptical that local anaesthetic infiltration would eliminate the pain of cannulation. Consequently a further study was undertaken to compare the pain of cannulation with and without the use of local anaesthetic. The results show that pain of cannulation is significantly (p < 0.003) reduced after subcutaneous infiltration with 1% lignocaine when compared to cannulation without local infiltration. Persistent discomfort at the site of cannulation was eliminated by the use of local anaesthetic. PMID- 1443487 TI - Day case laparoscopy. A comparison of two anaesthetic techniques using the laryngeal mask during spontaneous breathing. AB - Forty women undergoing day case laparoscopy were randomly allocated to receive either an inhalational or total intravenous anaesthetic. All patients breathed spontaneously through a Brain laryngeal mask. There were no clinically significant cardiovascular or respiratory differences between the two techniques. No episodes of clinical aspiration occurred and there were no peri-operative arrhythmias. We conclude that spontaneous respiration with a laryngeal mask is a safe and effective method of anaesthesia for laparoscopy provided certain guidelines are followed. PMID- 1443488 TI - An audit of induction of anaesthesia in neonates and small infants using pulse oximetry. AB - The frequency and severity of hypoxaemia during induction of anaesthesia in neonates and small infants at the Norfolk and Norwich Hospital, a district general hospital, was compared, using pulse oximetry, with that of the nearest specialist hospital, the Queen Elizabeth Hospital for Sick Children in London. There were differences in staffing and the choice of anaesthetic techniques between the hospitals. One third of the patients in both hospitals experienced desaturation of more than 5% (moderate or severe hypoxaemia) at one or more recordings during induction. The highest incidence of hypoxaemia was associated with awake intubation. There was no statistical difference in the incidence or severity of hypoxaemia between the hospitals. In the district general hospital, moderate or severe hypoxaemia of greater than 30 s duration was more likely if an anaesthetist with a regular paediatric operating list was not present at induction (p < 0.01). PMID- 1443489 TI - Patient controlled analgesia--assessment of machine feedback to patients. AB - The effect of varying patient-controlled analgesia machine feedback was studied in two groups of patients following a standard surgical procedure using patient controlled analgesia with morphine to control postoperative pain. Analgesic demands, morphine consumption, pain scores and side effects were compared and comments from the patients were noted. There was no significant difference between those whose machines signalled only successful demands compared with those who had every demand acknowledged. The patients in the former group appreciated the extra input and the nursing staff found this machine configuration to be less disturbing to the ward. There was no evidence of a clinically useful placebo effect in the latter group. PMID- 1443490 TI - Spinal anaesthesia for urological surgery. A survey of failure rate, postdural puncture headache and patient satisfaction. AB - A survey was conducted on 100 consecutive patients who underwent spinal anaesthesia in our urology operating theatres. Details of the spinal technique were recorded in the operating theatre. In 25% of patients, more than one attempt at subarachnoid puncture was required and 16% of this group went on to require general anaesthesia. The patients were visited between 24 and 48 h postoperatively by one of the authors. On questioning, 24% of patients reported a headache, which had the characteristics associated with dural puncture; 62% of these headaches were described as moderate or severe and lasted between 12 and 24 h. Patients were significantly (p < 0.05) more likely to develop a postdural puncture headache if more than one attempt at subarachnoid puncture was made. PMID- 1443491 TI - Shivering. PMID- 1443492 TI - Chemical meningism after lumbar facet joint block. PMID- 1443493 TI - Use of calcium chloride for propranolol overdose. PMID- 1443494 TI - Anaesthesia in the neuroleptic malignant syndrome. PMID- 1443495 TI - Airway obstruction and the laryngeal mask airway in paediatric radiotherapy. PMID- 1443496 TI - Laryngomalacia--a specific indication for the laryngeal mask? PMID- 1443497 TI - Spurious end-tidal CO2 diagnosed by capnogram. PMID- 1443498 TI - Failure of an Ohmeda OAV 7750 ventilator. PMID- 1443499 TI - Partial failure of a Servo 900C ventilator. PMID- 1443500 TI - Ventilators, circle systems and respirometers. PMID- 1443501 TI - Pulmonary oedema due to fentanyl? PMID- 1443502 TI - Atrial fibrillation after electroconvulsive therapy. PMID- 1443503 TI - Are the hazards associated with glass syringes justified? PMID- 1443504 TI - Nalbuphine--an analgesic with unique built-in safety feature. PMID- 1443505 TI - Sugi absorbent swabs, dacrocystorhinostomy and partial respiratory obstruction. PMID- 1443506 TI - [S-(+)-ketamine. The beginning of a new ketamine era?]. PMID- 1443507 TI - [The action of S-(+)-ketamine on serum catecholamine and cortisol. A comparison with ketamine racemate]. AB - The S(+)-isomer of ketamine has about twice the anaesthetic potency of the commercially available racemic mixture of ketamine. It is assumed that the known side-effects of ketamine are significantly reduced when administering half the usual dose with the same pharmacodynamic effect [17, 25]. The aim of the present study was to determine the haemodynamic effects, the catecholamine and cortisol plasma levels after administration of equally potent doses of S-(+)-Ketamine and racemic mixture of ketamine. In addition, the effect of premedication with i.v. midazolam was assessed. METHOD. After approval by the ethics committee and written informed consent, 30 healthy male volunteers were randomly allocated to three groups (n = 10). Group 1 received 2 mg/kg ketamine racemate, group 2 1 mg/kg S-(+)-Ketamine, and group 3 1 mg/kg S-(+)-Ketamine 5 min after i.v. premedication with 0.1 mg/kg midazolam. Non-invasive blood pressure (BP) and heart rate (HR) were continuously recorded. Blood samples were drawn 7 min before, and 2, 4, 8, 16, 32, 64 and 128 min after drug administration. Plasma epinephrine and norepinephrine (NE) levels were determined by HPLC and cortisol plasma levels by RIA. Data were analysed with the Kruskal-Wallis test (P < or = 0.05) for differences between groups. RESULTS. HR and BP showed a significant rise after injection of racemate and isomer, without any significant differences between groups. This was also seen for norepinephrine and cortical plasma levels. Epinephrine levels, however, differed between groups, showing a significant rise after racemate compared to isomer. Premedication with midazolam, in contrast, blunted major haemodynamic and hormonal changes. DISCUSSION. The haemodynamic changes did not differ between the racemate and isomer group despite a reduced isomer dose. HR and BP rise were similar, although epinephrine levels were significantly lower after isomer than racemate. Hence we assume that the increase in the haemodynamic parameters were mainly caused by NE. Midazolam apparently prevented the centrally mediated sympathetic stimulation caused by ketamine and its isomers. Therefore, i.v. premedication with midazolam should be applied when racemate or isomer is used, especially in high-risk cardiac patients. PMID- 1443508 TI - [Studies using S-(+)-ketamine on probands. Computerized EEG-analysis and transcranial Doppler ultrasonography]. AB - It has been shown in the recent literature that the anaesthetic potency of the ketamine isomer S(+)-ketamine is twice that of the racemic mixture used in clinical practice. METHODS. With approval of the local ethics committee, we investigated the effects of a bolus injection of 2 mg/kg racemic ketamine or 1 mg/kg S(+)-ketamine, respectively, on the electroencephalogram (EEG) and transcranial Doppler sonography (TCD) of the middle cerebral artery in ten healthy volunteers by means of a randomised, double-blind, cross-over design. Spectral edge frequency, total activity and activity of the alpha, beta, delta, and theta bands were assessed by bihemispheric leads using the Neurotrac system before (MZP 1) and 1, 3, 5, 10, 15, 30, 60, and 120 min after injection (MZP 2 9). Simultaneously, systolic (Vs-MCA), diastolic (Vd-MCA), and mean (Vm-MCA) blood flow velocities in the middle cerebral artery and pulsatility (Vs-Vd)/Vm were recorded. Statistics consisted of two-dimensional analysis of variance with P < 0.05 considered as significant. RESULTS. Racemic ketamine and S(+)-ketamine produced comparable effects on the EEG. Theta- and beta-activities increased between the 1st and 10th min after injection and returned to near baseline values thereafter. 120 min after injection, the absolute delta- and theta-activities were higher following racemic ketamine when compared to the S(+)-ketamine group. However, significant differences between the groups could not be confirmed statistically. TCD variables changed considerably in the course of the study without intergroup differences. Compared to the baseline values, Vs-MCA, Vd-MCA, and Vm-MCA increased significantly for the first 15 min after injection with a maximum at MZP 3. The pulsatility of the obtained Doppler waveform (Vs-Vd)/Vm showed significant decreases at MZP 2-4. CONCLUSIONS. In our study, both racemic ketamine and its isomer S(+)-ketamine produced similar EEG changes consistent with the data from earlier studies. However, the relative lower proportion of slow EEG activity at the end of the study might indicate a better recovery of cortical function following S(+)-ketamine than after racemic ketamine. Assuming a close relationship between cerebral blood flow velocity and cerebral blood flow, our TCD results suggest that both racemic ketamine and S(+)-ketamine will considerably increase cerebral blood flow in spontaneously breathing volunteers. Such an effect has been observed by others and, at least partly, can be explained by a concomitant increase in arterial carbon dioxide partial pressure. PMID- 1443509 TI - [Ketamine racemate or S-(+)-ketamine and midazolam. The effect on vigilance, efficacy and subjective findings]. AB - Ketamine is a racemic mixture containing equal amounts of optical isomers that have almost identical pharmacokinetic properties but different pharmacodynamic effects. The S-(+)-isomer of ketamine has about twice the anaesthetic and analgesic potency of the racemic ketamine preparation and is judged to induce less psychic emergence reactions and to be followed by a more rapid recovery of vigilance. The present study was designed to assess whether the S-(+)-isomer of ketamine is superior to the racemic mixture in cardiovascular characteristics, emergence reactions and cognitive functions, and whether side effects may be reduced or prevented by administration of midazolam prior to injection of S-(+) ketamine. METHODS. Following ethics committee approval and informed consent, 30 volunteers were randomly allocated in this double-blind study to three groups of 10 each. Group 1 received 2 mg/kg bw racemic ketamine, group 2, 1 mg/kg bw S-(+) ketamine and group 3, 1 mg/kg bw S-(+)-ketamine after premedication with 0.1 mg/kg midazolam i.v. Cardiovascular changes, state of vigilance, cognitive performance, subjective mood and acceptance of anaesthesia were assessed by means of haemodynamic routine monitoring, electroencephalography (EEG), psychometric tests and interview. RESULTS. The increases in mean arterial pressure and heart rate following the injection of racemic ketamine and S-(+)-ketamine were identical and the differences from baseline values significant after both. Premedication with midazolam ensured stable haemodynamics after injection of S (+)-ketamine. EEG analysis displayed the characteristic changes well known from ketamine anaesthesia for both racemic and S-(+)-ketamine. The vigilosomnoscript showed an identical profile of vigilance up to 30 min after injection of both drugs. The vigilance status after 125 min was less impaired by S-(+)-ketamine than by racemic ketamine. Psychological assessment showed a prompter recovery of visual attentiveness and sensorimotor performance in the S-(+)-ketamine group. Subjective mood was judged by the volunteers to be significantly better after S (+)-ketamine, and volunteers found S-(+)-ketamine to be more acceptable than racemic ketamine. The frequency of dreams was the same after both drugs. No unpleasant dreams were reported after S-(+)-ketamine, but one of the volunteers who received racemic ketamine had uncomfortable dreams. Midazolam prevented any unpleasant emergence sequelae. On the other hand, the cognitive performance could not be restored to the baseline values until at least 240 min after injection of S-(+)-ketamine, because of the sedative effects of midazolam. DISCUSSION. These results suggest that S-(+)-ketamine offers the advantages of faster recovery of cognitive performance, greater acceptance by the volunteers and identical depth of anaesthesia after injection of half the dose compared with racemic ketamine. The clinical use of S-(+)-ketamine therefore seems to be justified. Premedication with benzodiazepines, e.g. midazolam, is essential. The dose to be administered, however, should be carefully selected in order not to abolish the positive effect of S-(+)-ketamine on vigilance by the sedative effects of the benzodiazepine. PMID- 1443510 TI - [The simultaneous determination of ketamine and midazolam using high pressure liquid chromatography and UV detection (HPLC/UV)]. AB - In order to prevent some negative side effects of ketamine during "dissociative anaesthesia", this substance is regularly combined with benzodiazepines, e.g., midazolam. This study was undertaken to develop a simple and effective method for the simultaneous detection of ketamine and midazolam in plasma by high-pressure liquid chromatography with UV-detection (HPLC/UV). METHODS. The chromatographic system consisted of a 300 x 3.9-mm C18 column for reversed-phase chromatography and a mobile phase of 30% acetonitrile and 70% 0.05 M sodium phosphate buffer, pH 4.45. The flow rate was 1 ml/min. UV-detection took place at a wavelength of 210 nm. Blood samples were preferably taken from a central venous or arterial line. After plasma separation, 1 microgram (100 microliters) etidocaine was added to 1 ml plasma as an internal standard. The samples were alkalinised and extracted with ether, followed by back-extraction of the organic phase in 250 microliters 0.05 N sulphuric acid; 50 microliters of this solution was injected into the system. RESULTS. Sample preparation by trained personnel was reliable and led to adequate results. Separation of ketamine and midazolam was very satisfactory. Standard curves for both drugs were linear from 15-4000 ng/ml (ketamine r = 0.9998; midazolam r = 0.9996). Recovery rates for ketamine in plasma were above 95%, for midazolam 70%-75%. Coefficients of variation for ketamine in plasma were between 0.6% and 1.3%, for midazolam between 2.0% and 2.6%. The detection limit was lower than 5 ng/ml. CONCLUSION. The method is suitable for clinical practice and allows the simultaneous detection of two anaesthetics in wide-spread combined use. PMID- 1443511 TI - [Cerebral effects of ketanserin. The influence on hemodynamics and brain metabolism]. AB - Ketanserin, a 5HT2- and alpha 1-receptor antagonist, decreases blood pressure by decreasing systemic vascular resistance without causing reflex cardiac stimulation, while cardiac output remains unchanged. To date, little is known about the effects of ketanserin on cerebral haemodynamics and cerebral metabolism. According to a recently published study, ketanserin seems not to impair cerebral blood flow autoregulation in man. The present study was designed to investigate the influence of ketanserin on cerebral circulation and metabolism, and the cerebrovascular response to CO2 in man. METHODS. Twenty male patients between 44 and 67 years of age who were scheduled for coronary artery bypass surgery were randomly allocated to one of two groups. In group 1 measurements were performed after induction of anaesthesia during normocapnia (p(a) CO2 approximately 40 mm Hg) and hypocapnia (p(a) CO2 approximately 30 mm Hg). Then, ketanserin was given at a bolus dose of 0.3 mg.kg-1 followed by an infusion of 0.06 mg.kg-1.h-1 and measurements were repeated under hypocapnic and normocapnic conditions. Patients of group 2 were hyperventilated at first, then normoventilated. Afterwards, ketanserin was administered at the above-mentioned dose and measurements were again performed during normocapnia and hypocapnia. Cerebral blood flow (CBF) was measured using the argon wash-in technique. Cerebral venous blood was obtained from a catheter in the superior bulb of the right internal jugular vein. Cerebral perfusion pressure (CPP) was calculated by subtracting jugular bulb pressure from mean arterial pressure and cerebral vascular resistance (CVR) by dividing CPP by CBF. Cerebral metabolic rates of oxygen, glucose, and lactate were calculated by multiplying the arterial-cerebral venous oxygen and substrate differences by CBF. RESULTS AND DISCUSSION. Ketanserin decreased CPP by 16% to about 60 mm Hg. Cerebral blood flow remained unchanged as a result of an insignificant decline in CVR. Hyperventilation increased CVR by 32%, while CBF decreased by 27% to the same value that had been obtained during hypocapnia without ketanserin. The percentage changes in CBF per mm Hg change in CO2 were 1.45%/mm Hg (group 1 and 2.91%/mm Hg (group 2), respectively, without ketanserin and 1.98%/mm Hg and 2.22%/mm Hg with ketanserin. As CO2-responsiveness with ketanserin was higher in group 1 but lower in group 2 than without ketanserin, the direction in which ventilation was changed rather than ketanserin was responsible for these changes in CO2-responsiveness. Neither during normocapnia nor during hypocapnia did ketanserin have any effects on cerebral metabolic activity. Thus, it can be concluded that ketanserin does not impair CBF regulation and metabolism and that cerebral vascular responsiveness to hypocapnia is preserved. PMID- 1443512 TI - [Continuous peridural anesthesia in abdominal surgery. An alternative for elderly patients]. AB - Being advanced in years is not in itself a high risk in anaesthesia; however, altered pharmacokinetics and pharmacodynamics, mental dysfunction and the administration of anaesthetics complicate the postoperative period. In order to examine the problem of sedation in elderly patients, we studied the effects and side effects of continuous peridural anaesthesia for abdominal surgery. METHODS. On the day before surgery we inserted a peridural catheter (Perifix 400, Braun, Melsungen, FRG) between T-12 and L-4 in 52 patients in a sitting position (mean age 69.3 +/- 10.9 years) using the loss-of-resistance technique. If no signs of spinal anaesthesia became apparent, the exact position of the catheter was determined using 9 or 10 ml bupivacaine 0.5%. Next day, after premedication with atropine, pethidine or midazolam, 20-25 ml bupivacaine 0.5% was instilled through the peridural catheter. During surgery patients were sedated using a small dose of propofol. We also insufflated oxygen (2 l/min). Blood pressure, heart rate, and blood gases were monitored and electrocardiography and pulse oximetry performed. As postoperative pain therapy, we administered morphine through the peridural catheter at intervals of 8 h. For statistical evaluation we used Wilcoxon's test. RESULTS. An adequate degree of analgesia was found between T-4 and T-7 and abdominal muscle relaxation was satisfactory. Heart rate decreased by 10.3% after the administration of local anaesthetics. After surgery had begun, blood pressure decreased over a period of 30 min (systolic by 20.5% and diastolic by 14.2%) but it remained constant at this level during the rest of the operation (see Fig. 1). Neither of these side effects was significant. Oxygen saturation and blood gases were normal. During the operation, a mean dose of 325 mg propofol/h was necessary to maintain sedation. After surgery all patients were awake, suffered no pain and had complete amnesia with regard to the operation. The postoperative peridural dosage of 5 mg morphine (three times in 24 h) was very effective. Because some patients vomited we used between 50 and 100 mg tramadol (four times in 24 h) instead of morphine. Early mobilization of patients was possible and there were no pulmonary complications such as pneumonia. CONCLUSIONS. If carried out by an experienced physician, continuous peridural anaesthesia can be an alternative method in abdominal surgery for elderly patients. We see advantages in the minimal disturbance of pulmonary and mental function, in the minimal amount of sedation required and in the successful postoperative pain therapy. PMID- 1443513 TI - [Combined sciatic 3-in-1 block. Application in lower limb orthopedic surgery]. AB - The effects of increasing the maximum prescribed volume of 50 ml lidocaine 1% to 65 ml in a combined sciatic 3-in-1 block were investigated in 25 adult patients. The goal of the study was (1) to show possible increase in the success rate and (2) to determine if toxic plasma levels of local anaesthetic would be reached. Further more, we wanted to find out if there were any side-effects. The patients were divided into three groups according to body weight: group I, 50-69 kg (n = 7); group II, 70-80 kg (n = 9); group III, over 80 kg (n = 9). Besides clinical observation, the plasma levels of local-anaesthetic were determined over a 90-min period. RESULTS. Following the neural blockade, the obturator nerve was the first to be rendered insensitive after 4.8 +/- 3.6 min, followed by the saphenous (7.2 +/- 4.4 min) and femoral nerves, and finally by the lateral femoral cutaneous nerve after 12.5 +/- 5.3 min. Around the knees, the motor blockade was complete after 11.9 + 4.3 min and around the hips 11.2 +/- 4.6 min. Intraoperatively, one of these 25 patients needed an additional general anaesthetic, as he did not tolerate the Esmarch cuff. The postoperative analgesia in 24 patients lasted 268 +/- 55 min; the patient who had a general anaesthetic in addition had a postoperative analgesia of 315 min. Group I showed levels of mean 2.04 +/- 0.64 microns/ml, group II 1.84 +/- 0.38 microns/ml and group III 1.69 +/- 0.63 microns/ml. There were no statistical differences between the three groups. CONCLUSION. Increasing the dosage of lidocaine from 500 to 650 mg makes the block very successful without any toxic side-effects. PMID- 1443514 TI - [Obstructive respiration disorders. An aneurysm of the ventilator tubing during general anesthesia]. AB - Technical problems during anaesthesia are important causes of anaesthesia-related deaths and brain damage. During general endotracheal anaesthesia for ophthalmic surgery (41-year-old man, ASA 1) we observed an increase in inspiratory pressure without other clinical changes. Disconnection and ventilation with a resuscitation bag showed normal inspiratory pressures. Inspection demonstrated an obstruction due to an aneurysm of the inner layer of the inspiratory tubing. The classification of this rare blockage of ventilation differs in the literature (pressure, hypoventilation, hypercarbia). In addition, it demonstrates the principal problem of clinical decision-making during anaesthesia based on monitoring information. Strategies for responding to alarms indicating hazards of ventilation must be based on immediate restoration of sufficient ventilation, and not primarily on detecting the cause. PMID- 1443515 TI - [Comments on the paper by H.-J Hartung and Th. Luiz. Total spinal anesthesia]. PMID- 1443516 TI - [Comments on the paper by T. Menges et al. Methods of limiting the use of donor blood]. PMID- 1443517 TI - [Positive end-expiratory pressure (PEEP)]. AB - PEEP has become a widely used ventilatory technique. The beneficial effects of PEEP were first described in asphyctic neonates, and it was later used in the treatment of cardiogenic pulmonary edema. Since the 1970s PEEP has been well established for the treatment of ARDS; the technique is also used for scoring the degree of severity of ARDS. Two mechanisms have been identified to explain pulmonary function and gas exchange following PEEP therapy: increasing FRC and alveolar recruitment. Both factors result in improvement in the ventilation/perfusion ratio with a consequent decrease in the intrapulmonary right-to-left shunt fraction. PEEP should be used in cardiogenic pulmonary edema as well as in ARDS; there are few contraindications. To choose the individual level of PEEP, PEEP should be titrated in 3- to 5-cm increments and its effects on haemodynamic function, pulmonary gas exchange and respiratory mechanics taken into account. In this article the effects of PEEP, its use and abuse are reviewed from a practical point of view. PMID- 1443518 TI - Quantitation of CoASH and acyl-CoA. PMID- 1443519 TI - Investigation of noncalcium interactions of fura-2 by classical and synchronous fluorescence spectroscopy. AB - Several authors have reported unexpected intracellular spectra of both indo-1 and fura-2. One of the major methodological problems in the evaluation of calcium concentration using fluorescent probes is that it is assumed that only two forms of the dyes are detectable within the cells. We show in this study of fura-2 properties that this calcium probe is pH-sensitive and able to bind to cellular proteins. The excitation spectra of protonated and protein-bound forms of fura-2 exhibit a maximum in the same region as that associated with the calcium-free form (i.e., near 365 nm). The very small shift in the excitation spectra upon proton or protein binding precludes the use of classical methods to determine the spectral composition of mixtures of several forms of fura-2. We therefore used the synchronous fluorescence technique to detect the protein-bound form of fura-2 selectively, in order to assess the pH dependence of the fura-2/protein interaction. The nonspecific binding of fura-2 to proteins is reinforced at acidic pH and inhibited by calcium. The fact that the same type of interaction was found between fura-2 and poly-L-lysine suggests that it could be mediated by basic amino acids. Because of the strong overlap of the excitation spectrum of the unprotonated free fura-2 with those associated with the protonated and protein-bound forms, a cytoplasmic acidification may lead to an artifactual measurement of low calcium levels. PMID- 1443520 TI - Factors controlling variability in measurements of the transient gene expression in electroporated protoplasts of wheat callus. AB - Factors controlling variability in enzyme transient expression assays have been investigated in electroporated protoplasts isolated from wheat embryogenic and nonembryogenic calli. The level of variation was reduced to a minimum through the optimization of the beta-glucuronidase measurements in the pellet and the supernatant of the homogenized protoplasts, by expressing the data on the basis of the number of protoplasts found to be viable immediately before the assay and on the amount of protein in the pellet and supernatant. Protoplast separation on the basis of size was also useful in eliminating some of the variation resulting from the heterogeneity of the callus used. Efforts to partially synchronize the callus tissue by auxin starvation have not resulted in a significant decrease of this variation. Our results indicate that the level of variation in enzyme transient activity in protoplasts resulting from calli can be reduced by implementation of the experimental techniques presented here. PMID- 1443521 TI - Effect of covalent modification on the binding of cholera toxin B subunit to ileal brush border surfaces. AB - A competitive binding assay has been developed to determine how modifications to the B subunit of cholera toxin affect the binding affinity of the subunit for an ileal brush border membrane surface. The Ricinus communis120 agglutinin (RCA120) specifically binds to terminal beta-D-galactosyl residues such as those found in oligosaccharide side chains of glycoproteins and ganglioside GM1. Conditions were designed to produce binding competition between the B subunit of cholera toxin and the RCA120 agglutinin. Displacement of RCA120 from brush border surfaces was proportional to the concentration of B subunit added. This assay was used to study the effect of modification of B subunit on competitive binding affinity for the ileal brush border surface. The B subunit of cholera toxin was modified by coupling an average of five sulfhydryl groups to each B subunit molecule and by reaction of the SH-modified B subunit with liposomes containing a surface maleimide group attached to phosphatidylethanolamine. SH-modified B subunit was approximately 200-fold more effective than native B subunit in displacing lectin from brush border surfaces in the competitive binding assay. The enhanced binding activity was retained on covalent attachment of the modified B subunit to the liposome surface. We conclude that the B subunit of cholera toxin may be a useful targeting agent for directing liposomes to cell surfaces that contain a ganglioside GM1 ligand. PMID- 1443522 TI - The measurement of negative charge content in cartilage using a colloid titration technique. AB - A colloid titration technique has been used to determine the sulfate and carboxylate content of various glycosaminoglycans and has been validated by comparing the results with data obtained using well-established techniques. The method has been applied to the measurement of the negative charge content of cartilage slices at various depths from the articular surface and to the determination of sulfate and carboxylate contents in bovine nasal septa. Titrations of nasal septa were performed on milled cartilage, on cartilage digested with papain and on proteoglycans purified by cesium chloride gradient centrifugation of guanidinium chloride extracts. The sulfate content was similar for all three preparations (0.5 mu eq per milligram dry cartilage). However, the carboxylate content determined on milled cartilage was 40% higher than that obtained for cartilage digested with papain or for purified proteoglycans; this implies the possible contribution of carboxyl groups from structural glycoproteins present in the extracellular matrix. The carboxylate content determined on purified proteoglycans was in excellent agreement with values calculated from chemical analyses. PMID- 1443523 TI - Fluorometric assay of 25-hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 in plasma. AB - The first practical fluorometric assay of plasma 25-hydroxyvitamin D3 (25-OH-D3) and 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) is described. The method uses a highly fluorescent dienophile, 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4 dihydroquinoxalyl)ethyl]-1, 2,4- triazoline-3,5-dione (DMEQ-TAD), to fluorescence label vitamin D. Vitamin D metabolites were roughly purified with a short cartridge column followed by HPLC, labeled with DMEQ-TAD, and the product was analyzed on HPLC. In the assay of 25-OH-D3 the new fluorometric method was compared with the HPLC-uv method and was confirmed to be as accurate and reliable (CV, 4-5%) as the HPLC-uv method. Plasma 24,25-(OH)2D3 was accurately assayed by the HPLC-FL method, where the standard addition method was successfully used to calculate the overall recovery. PMID- 1443524 TI - Simultaneous determination of sugar incorporation into glycosphingolipids and glycoproteins. AB - We assessed inhibitors of glycosylation by simultaneous determination of [14C]Gal incorporated into glycosphingolipids and glycoproteins as well as of [3H]Leu incorporated into proteins of intact cells. After metabolic labeling in 96-well plates in the presence or absence of a test substance, cells were collected on glass-fiber filters. The lipid components were extracted from the filter and radioactivities of both extract and filter determined. The reliability of the procedure was tested with different drugs. Using the glucocerebroside synthetase inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP; 5 microM), glycolipid biosynthesis was shown to be reduced to 50% in the murine T-cell EL-4 6.1 line, whereas glycosylation of proteins was not disturbed. With 0.5 microM tunicamycin, the glycosylation of proteins was 50% of that in the control. The procedure was also able to detect various specific effects: the inhibition of protein glycosylation with D-glucosamine and castanospermine, the inhibition of glycosphingolipid biosynthesis with L-cycloserine, and a slight enhancement of glycosphingolipid biosynthesis with conduritol B epoxide and castanospermine. Within a series of N-acyl homologs of PDMP the inhibitory potency increased with chain length. In contrast, these homologs were equipotent by enzymatic in vitro assays. PMID- 1443525 TI - Quantitation of positional isomers of deuterium-labeled glucose by gas chromatography/mass spectrometry. AB - A method for determining the site and extent of deuterium (D) labeling of glucose by GC/MS and mass fragmentography was developed. Under chemical and electron impact ionization, ion clusters m/z 328, 242, 217, 212, and 187 of glucose aldonitrile pentaacetate and m/z 331 and 169 of pentaacetate derivative were produced. From the mass spectra of 13C- and D-labeled reference compounds, glucose carbon and hydrogen (C-H) positions included in these fragments were deduced to be m/z 328 = C1-C6, 2,3,4,5,6,6-H6; m/z 331 = C1-C6, 1,2,3,4,5,6,6-H7; m/z 169 = C1-C6, 1,3,4,5,6,6-H6; m/z 187 = C3-C6, 3,4,5,6,6-H5; m/z 212 = C1-C5, 2,3,4,5-H4; m/z 217 = C4-C6, 4,5,6,6-H4; and m/z 242 = C1-C4, 2,3,4-H3. After correction for isotope discrimination and deuterium-hydrogen exchange, the D enrichment of these fragments can be quantitated using selective ion monitoring, and the D enrichment of all C-H positions can be obtained by the difference in enrichment of the corresponding ion pairs. The validity of this approach was tested by examining D enrichment of known mixtures of 1-d1-, 2-d1-, 3-d1-, and 5,6,6-d3-glucose with unlabeled glucose and D enrichment of perdeuterated glucose using these fragments. This method was used to determine deuterium incorporation in C1 through C6 of blood glucose in fasted (24 h) rats infused with deuterated water. The distribution of deuterium was similar to that found by Postle and Bloxham (1980, Biochem. J. 192, 65-73). Approximately one deuterium atom was incorporated into C5 and only 75% deuterium atom was incorporated into C2. The enrichment of C2 and C6 of glucose relative to that of water indicated that 74 +/ 9% of plasma glucose was newly formed 4 h after the onset of deuterium infusion, and gluconeogenesis accounted for about 76 +/- 7% of the glucose 6-phosphate flux. PMID- 1443526 TI - A specific peroxidase-coupled activity stain for diamine oxidases. AB - A specific peroxidase-coupled activity staining method for diamine oxidase (DAO) was developed. Diaminobenzidine was found to inhibit DAO and to give rise to unspecific staining. Among several other reagents 4-Cl-1-naphthol was found to be most suitable. Using specific activity staining DAO could be visualized in polyacrylamide gels as a high-molecular-weight complex, which could be dissociated by Tween 20 but not by NP-40, Triton X-100, or Chaps. PMID- 1443527 TI - Synthesis of [2-3H-ethyl]S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine and its use in covalent-binding studies. AB - Metabolism of S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) yields chlorofluorothioacetyl fluoride, which reacts with cellular proteins to form stable lysine adducts. Little is known about the subcellular localization of these protein adducts or about their role in CTFC-induced nephrotoxicity. A method for the synthesis of CTFC and other cysteine S-conjugates labeled with 3H at the S-alkyl or S-alkenyl position would be useful in studies of S-conjugate metabolism and toxicity. Reaction of L-cysteine, chlorotrifluoroethene, 1,8 diazabicyclo[5.4.0]undec-7-ene, and 3H-labeled water followed by repeated crystallization yielded radiochemically pure [3H]CTFC (235 mg, 20% yield; sp act 1.07 x 10(9) Bq/mmol), which was identical to CTFC by TLC, 1H NMR, and 19F NMR. 3H NMR revealed a doublet of triplets at 6.5 ppm with geminal and vicinal T-F couplings of 51.5 and 6.0 Hz, respectively, consistent with the proposed structure. When 2H-labeled water was used, [2H]CTFC was formed, and its structure was confirmed by 1H and 19F NMR, FAB-MS, and TLC. Analysis of renal and hepatic subcellular fractions of rats given 1, 10, or 100 mumol/kg [3H]CTFC showed a dose dependent binding of 3H-containing metabolites to liver and kidney proteins. PMID- 1443528 TI - An enzyme-reactor for electrochemical monitoring of choline and acetylcholine: applications in high-performance liquid chromatography, brain tissue, microdialysis and cerebrospinal fluid. AB - A sandwich-type enzyme reactor in which the enzymes are physically immobilized in a minimal dead space between two cellulose membranes, resulting in improved sensitivity, was developed for the electro-chemical detection of choline (Ch) and acetylcholine (ACh). The reactor contains the enzymes choline oxidase with or without acetylcholine esterase, for the detection of ACh and Ch, respectively. For the HPLC analysis of Ch and ACh the detection system was coupled post column. Levels of Ch and ACh of rat striatum tissue and human cerebrospinal fluid were found to be similar to those determined with published methods. Because of low back pressure--a further advantage of the reactor--the detection system could also be directly coupled to the outlet of a microdialysis device, allowing the on line real-time measurement of extracellular brain Ch. The versatility of the enzyme reactor for the monitoring of analytes in HPLC eluates, flow injection analysis, with or without prepurification, is emphasized. The usefulness of the reactor-detector system in biomedical applications is illustrated by the measurement of increases of rat striatal extracellular Ch following cardiac arrest. PMID- 1443529 TI - A potential pitfall in protein kinase assay: phosphocellulose paper as an unreliable adsorbent of produced phosphopeptides. AB - The ability of phosphocellulose paper to retain phosphorylated peptides containing basic amino acid residues was investigated. Some peptide substrates that are commonly used for three different protein kinases were tested. The adsorption onto phosphocellulose paper was strongly dependent on the amino acid composition of the peptides. None of the phosphopeptides studied was adsorbed completely, the amount bound varied from 7 to 93%. Phosphopeptides containing two basic amino acids each differed remarkably in the degree of binding to the phosphocellulose paper (40% RRASVA, 60% FRRLSI, and 80% HRASV was bound). The results presented here indicate that data from phosphorylation experiments obtained so far for different peptides using the phosphocellulose paper method should be judged with caution. PMID- 1443530 TI - Use of bacterial and firefly luciferases as reporter genes in DEAE-dextran mediated transfection of mammalian cells. AB - The aim of this study was to compare three different luciferase genes by placing them in a single reporter vector and expressing them in the same mammalian cell type. The luciferase genes investigated were the luc genes from the fireflies Photinus pyralis (PP) and Luciola mingrelica (LM) and the lux AB5 gene, a translational fusion of the two subunits of the bacterial luciferase from Vibrio harveyi (VH). The chloramphenicol acetyltransferase (CAT) gene was also included in this study for comparison. The performances of the assay methods of the corresponding enzymes were evaluated using reference materials and the results of the expressed enzymes following transfection were calculated using calibration curves. All of the bioluminescent assays possess high reproducibility both within and between the batches (less than 15%). The comparison of the assay methods shows that firefly luciferases have the highest detection sensitivity (0.05 and 0.08 amol for PP and LM, respectively) whereas the VH bacterial luciferase has 5 amol and CAT 100 amol. On the other hand, the transfection of the various plasmids shows that the content of the expressed enzyme within the cells is much higher for CAT than for the other luciferase genes. VH luciferase is expressed at very low levels in mammalian cells due to the relatively high temperature of growing of the mammalian cells that seems to impair the correct folding of the active enzyme. PP and LM luciferases are both expressed at picomolar level but usually 10 to 70 times less in content with respect to CAT within the transfected cells. On the basis of these results the overall improvement in sensitivity related to the use of firefly luciferases as reporter genes in mammalian cells is about 30 to 50 times with respect to that of CAT. PMID- 1443531 TI - Quantification of peptide aldehyde ligands immobilized for the affinity chromatography of endopeptidases. AB - A method is described for quantification of aldehyde and aldehyde semicarbazone groups attached to an insoluble matrix. Semicarbazones are converted to aldehydes, and the aldehydes are coupled with 4-phenylazoaniline. The excess reagent is washed off, and the remainder then displaced with salicylaldehyde. The quantity of the phenylazoaniline/salicylaldehyde adduct is determined spectrophotometrically, allowing the calculation of the amount of aldehyde or semicarbazone per unit volume of the matrix. Analyses by the new method show that four matrices offered commercially for this type of immobilization differ greatly in coupling capacity and stability of the conjugate under conditions of affinity chromatography. PMID- 1443532 TI - Modification of the bicinchoninic acid protein assay to eliminate lipid interference in determining lipoprotein protein content. AB - The bicinchoninic acid (BCA) assay method for the determination of protein has been investigated for its utility in measuring the protein content of plasma lipoproteins. Although other methods, principally those based on the method of Lowry et al. (1951, J. Biol. Chem. 193, 265-275) have been extensively used for this purpose, the tolerance of the BCA method to many commonly encountered detergents and buffers offers a definite advantage over the Lowry-based methods. In this study, lipoprotein protein values obtained by the BCA method were compared to a standard modification of the Lowry et al. procedure since this assay forms the basis of much of the relevant literature. The standard BCA assay was found to overestimate the protein content of very low density lipoprotein by approximately 70% and low density lipoprotein by approximately 30%; high density lipoprotein values compared favorably. Overestimations by the BCA assay paralleled the relative phospholipid content of the lipoprotein fractions. This apparent lipid effect was eliminated by the addition of 2% sodium dodecyl sulfate to samples prior to the analysis. In the presence of this detergent, BCA assay measurements for these three lipoprotein fractions were 97, 90, and 98%, respectively, of the reference assay values. PMID- 1443533 TI - Ion-spray tandem mass spectrometry in peptide synthesis: structural characterization of minor by-products in the synthesis of ACP(65-74). AB - Ion-spray triple quadrupole mass spectrometry was used to investigate the products from the solid phase synthesis of the decapeptide (H)-Val-Gln-Ala-Ala Ile-Asp-Tyr-Ile-Asn-Gly-(OH) [acyl carrier protein(65-74)]. The target sequence was assembled in stepwise fashion from the C-terminal using Boc chemistry on a Bly-OCH2-Pam-copoly(styrenedivinylbenzene) resin. The product was deprotected and cleaved from the resin by treatment with HF/p-cresol for 1 h at 0 degrees C. The crude product was analyzed by reverse-phase HPLC and contained a single major peptide component, one significant minor (late-eluting) component and several trace-level peptide by-products. The components were separated by HPLC and the fractions directly analyzed by mass spectrometry and tandem mass spectrometry. The major product was confirmed as the desired ACP(65-74). The significant minor component was apparently from incomplete deprotection of Asp70, an artifact of this particular experiment. The trace by-products were found to arise from succinimide formation at Asp70, succinimide formation at Asn73, acylation of the Tyr71 side chain phenolic hydroxyl leading to a branched heptadecapeptide, and tert-butylation of the decapeptide. The possible origins of these by-products are discussed in light of known peptide chemistry. Also notable was the absence, to very low detection levels, of by-products frequently reported to occur in peptide synthesis, illustrating the high degree of refinement and the accuracy of currently used synthetic methods. PMID- 1443534 TI - Synthesis and properties of N-bromoacetyl-L-thyroxine. AB - A one-step bromoacetylation of L-thyroxine (T4) produces N-bromoacetyl-L thyroxine (BrAcT4) in good yield. The reaction product is best purified by high speed countercurrent chromatography. While HPLC is satisfactory only for purification of microgram and submicrogram quantities, amounts ranging from about 1 ng to 1 g of BrAcT4 can be processed by high-speed countercurrent chromatography (HSCCC), a method which we have previously used for the purification of N-bromoacetyl-3,3',5-triiodo-L-thyronine (BrAcT3). Operating conditions for the one-step synthesis of BrAcT4 and BrAcT3 differ due to differences in solubility and reactivity of the two hormones. BrAcT4 purified by HSCCC and shown to be pure by analytical HPLC has been characterized by alpha max and epsilon max in the near and far uv in several solvents, mass spectrum, 1H NMR spectrum, TLC in three solvent systems, retention time in reverse-phase HPLC (C18) in relation to the retention times of two internal standards, 3,3',5 triiodo-L-thyronine and T4, and melting point. Corresponding data for BrAcT3, not previously reported, have also been determined. The described procedure can provide not only substantial amounts of highly purified BrAcT4 for competition studies, but also 125I-labeled BrAcT4 of high specific activity for affinity labeling. Since solutions of BrAcT4 and of BrAcT3 undergo partial decomposition on evaporation to dryness, suitable procedures for the preparation of these hormones in solid form and for storage in solutions have been devised. PMID- 1443535 TI - A flow-cytometric method for the separation and quantitation of normal and apoptotic thymocytes. AB - Using flow cytometry, we describe a method for separating and quantifying normal and apoptotic thymocytes. Apoptosis was induced in isolated thymocytes from immature rats by treatment with the glucocorticoid dexamethasone or the antitumor agent etoposide. Subsequent incubation with the vital bisbenzimidazole dye Hoechst 33342 and the DNA intercalating agent propidium iodide enabled three distinct populations of cells to be identified and sorted by flow cytometry. Dead cells fluoresced red due to propidium iodide whereas normal and apoptotic cells fluoresced blue due to Hoechst 33342. Apoptotic cells were distinguished from normal thymocytes both by their higher intensity of blue fluorescence and by their smaller size as determined by a reduction in forward light scatter. The larger cells, with low blue fluorescence, showed normal thymocyte morphology by electron microscopy and the absence of any DNA fragmentation as measured by agarose gel electrophoresis. In contrast, the smaller cells showed both the morphological characteristics of apoptosis and extensive internucleosomal fragmentation of DNA to multiples of approximately 180 bp. Using this method, a time-dependent induction of apoptosis by dexamethasone, which was inhibited by cycloheximide, actinomycin D, and aurin tricarboxylate, was observed. The method should facilitate mechanistic studies on the induction of apoptosis in thymocytes. PMID- 1443536 TI - Selective enrichment and characterization of high affinity ligands from collections of random peptides on filamentous phage. AB - Large collections of random peptides can be expressed on the N-terminus of the pIII protein of filamentous phage and screened for binding to antibodies and other receptors. In our previous work with a monoclonal antibody (3E7) (Cwirla et al., Proc. Natl. Acad. Sci. USA 87, 6378-6382, 1990), we showed that a high proportion of the selected peptides had relatively low affinity (Kd's greater than 1 microM). Here we describe conditions for selective enrichment of phage expressing high affinity peptides. This is done by allowing the phage to interact with a low concentration of 3E7 Fab followed by extensive washing to allow dissociation of phage-bearing peptides with low affinity. These affinity selection conditions were applied to the pool of phage previously selected using a high concentration of IgG. A phage clone with the known high affinity ligand YGGFL (Kd 7.1 nM) and several other closely related peptides were isolated. The dissociation rate of 125I-3E7 Fab from several phage clones approximated that of phage expressing YGGFL. A good correlation was found between the dissociation rate of the peptides found on phage and the equilibrium binding constants of chemically synthesized peptides. The strategy of using a low concentration of receptor and extensive washing to select phage-bearing high affinity peptides, combined with assays to determine the specificity and relative affinity of peptides on isolated phage clones, should be generally applicable in using the peptides-on-phage system for discovery of high affinity receptor ligands. PMID- 1443537 TI - Novel synthesis of S-nitrosoglutathione and degradation by human neutrophils. AB - S-nitrosoglutathione (SNO-GSH), a stable derivative of nitric oxide, is an endothelium-derived relaxation factor, which provokes vasodilation, inhibits platelet aggregation, and inhibits neutrophil (PMN) superoxide anion (O2+) generation. We have established a novel method for synthesis of S nitrosoglutathione using a column containing S-nitrosothiol covalently attached to agarose. S-nitrosoglutathione was a product as assessed after separation using C-18 reverse-phase HPLC and absorption spectroscopy. We examined the stability of SNO-GSH in the presence or absence of PMN. The half-life (mercuric acid diazotization) of SNO-GSH in Hepes was greater than 60 min. The addition of resting PMN did not affect the T1/2 of SNO-GSH. PMN exposed to N-fMet-Leu-Phe (FMLP, 10(-7) M) reduced measurable SNO-GSH (15 microM) at 5 min (48 +/- 5.0% control, P less than 0.05). Incubation (5 min, 37 degrees C) of PMN with 10 microM tenidap (an anti-inflammatory drug which inhibits PMN activation) before addition of FMLP blocked the PMN-dependent degradation of SNO-GSH (42 +/- 3 vs 78 +/- 1.3% control, P = 0.01). We confirmed the recovery of SNO-GSH through measurements by bioassay (platelet aggregation) and HPLC analysis. The degradation of S-nitrosothiols by activated neutrophils may reverse the inhibitory effect of S-nitrosothiols on PMN functions and contribute to tissue injury at sites of inflammation. PMID- 1443538 TI - Development of an avidin-biotin competitive inhibition assay and validation of its use for the quantitation of human intervertebral disc serine proteinase inhibitory proteins. AB - A simple convenient method has been developed for the quantitation of serine proteinase inhibitors (SPIs) in tissue extracts. The method is based on the competitive binding to trypsin and chymotrypsin immobilized using glutaraldehyde on 96-well microtiter plate wells of native SPIs and a biotinylated secretory proteinase inhibitor (SLPI) standard. The bound SLPI standard was visualized using an avidin-alkaline phosphatase conjugate and inhibition curves were determined using absorbancy measurements at 405 nm. The standard assay had a range between 0.02 and 1 microgram SLPI/well and a lower detection limit of 20 ng SLPI/well; an improved microassay had a detection limit of 2 ng SLPI/well. Only active free inhibitor was detected in the assay since denatured and/or enzyme inhibitor complexes did not bind to the plates. A range of SPI species was demonstrable in human bronchial mucus and intervertebral disc SPI samples using this technique. Quantitation of SPI levels in a number of intervertebral disc samples indicated that the SPIs were depleted in degenerate discs compared to nondegenerate discs (P less than 0.05, n = 12). Since the immobilized trypsin and chymotrypsin microplates used in this assay may be prepared in advance (and are stable at 4 degrees C for at least 1 month) the remaining two steps of the assay (the inhibition step and visualization) may be completed in 2-3 h; thus the assay is simple, convenient, and fast. All reagents (other than the biotinylated SLPI standard) are readily available commercially, and in principle the assay could be adapted to other systems provided defined biotinylated standards were available. PMID- 1443539 TI - High-performance liquid chromatographic assays for free and phosphorylated derivatives of the creatine analogues beta-guanidopropionic acid and 1-carboxy methyl-2-iminoimidazolidine (cyclocreatine). AB - Creatine and phosphocreatine are substrates for creatine kinase which is a key enzyme involved in energy transfer within the cell. Analogues of creatine have been fed to animals to determine the role this enzyme plays in energy metabolism, but progress in interpretation has been hampered by the lack of quantitative techniques to determine tissue content of these compounds. We describe the separation and quantitation of substituted guanidino compounds and their phosphorylated forms by high-performance liquid chromatography. First, a cation exchange column is used to assay free creatine and its unphosphorylated analogues, and then phosphocreatine and its phosphorylated analogues as well as adenylate content (AMP, ADP, ATP) are assayed on an anion-exchange column. These methods have proven successful in measuring the chemical contents of these compounds in neutralized perchloric acid extracts of mammalian skeletal muscles. The sensitivity of this method ranges from 50 to 200 pmol, which is adequate to provide information from tissue extracts of 5- to 10-mg samples. PMID- 1443540 TI - Sulfated proteoglycans of rabbit aorta: selective extraction and alternative method for glycosaminoglycan moiety analysis. AB - Three different solutions containing urea, guanidine hydrochloride, or a detergent mixture were used to extract proteoglycan molecules (PG) metabolically labeled with 35S from normal rabbit aortic tissue. The size distribution of whole sulfated PG and the glycosaminoglycan (GAG) compositions in the three extracts were compared and found to be characteristically determined by the type of solution used for extraction. The spectrum of sulfated PG isolated by each solution was maintained at consecutive extractions of the tissue, even if this was used after another type of solution. The extracts obtained by using the urea- or guanidine-containing solutions contained similar, rather balanced populations of large and small PG, while the detergent-containing buffer was found to preferentially extract smaller, heparan sulfate-rich aortic PG. The selectivity of various extracting solutions could be exploited to obtain preparations enriched in certain types of sulfated PG. On the other hand, one could obtain a larger variety of 35S-labeled PG from the tissue by consecutively using two solutions with different capacities of extraction. The distribution of GAG moieties among PG populations, separated by size chromatography, was investigated by one of the commonly used methods and by a new method. The standard method is based on comparison of the chromatographic profiles of the extract before and after enzymatic digestions, requiring several chromatographic runs for a sample. In the alternative method proposed, the fractions obtained after a single chromatographic separation are adsorbed onto a support membrane. Processing of the whole membrane by GAG-specific, enzymatic treatments allows simultaneous assessment of GAG types in each fraction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443541 TI - Application of a novel apparatus, the quartz chemical analyzer, to the determination of endotoxin in blood. AB - A novel apparatus called a quartz chemical analyzer (QCA) has been developed using a quartz crystal resonator. This apparatus measures sample viscosity changes based on resonant frequency changes of the quartz crystal. The apparatus was used to determine bacterial endotoxin concentrations by monitoring the gelation reaction of Limulus amebocyte lysate. The QCA determined endotoxin concentrations with good accuracy and reproducibility in the range of 0.001-3 EU/ml for endotoxin standard (JP XII). For endotoxin determination in human whole blood and plasma samples, the inhibitory reaction was eliminated by pretreatment of a fourfold dilution at 60 degrees C and incubation for 30 min. There are many advantages of the QCA method compared with the turbidimetric and chromogenic methods. For example, QCA can measure sample viscosity changes with high sensitivity and accuracy because QCA detects minor resonant frequency changes and the frequency data give a numerical value for easy quantitation. QCA can examine turbid samples, and the required quantities of samples and reagents are small, since the quartz crystal detects sample viscosity changes directly. The endotoxin determination time may be shortened by raising the reaction temperature, and QCA can detect other types of coagulation reactions. PMID- 1443542 TI - Quantitation of low levels of IgM by electroimmunoassay. PMID- 1443544 TI - Custom-made adapters in silicone rubber for low-speed centrifugation. PMID- 1443543 TI - A means of distinguishing between specific hybridoma cDNA and cDNA of the myeloma cell fusion partner. PMID- 1443545 TI - A general method for the detection and quantitation of antigens in solubilized cells using radiolabeled Fab fragment. PMID- 1443546 TI - Spectroscopic quantitation of organic isothiocyanates by cyclocondensation with vicinal dithiols. AB - Organic isothiocyanates are widely distributed in plants and are responsible for a variety of beneficial and toxic biological effects. No direct and generic method for quantitating isothiocyanates has been described. Under mild conditions nearly all organic isothiocyanates (R-NCS) react quantitatively with an excess of vicinal dithiols to give rise to five-membered cyclic condensation products with release of the corresponding free amines (R-NH2). The products of the condensation of propyl-NCS with 1,2-ethanedithiol, 2,3-dimercaptopropanol, and 1,2-benzenedithiol have been isolated and identified as 1,3-dithiolane-2-thione, 4-hydroxymethyl-1,3-dithiolane-2-thione, and 1,3-benzodithiole-2-thione, respectively. Since 1,3-benzodithiole-2-thione (lambda max 365 nm and alpha m 23,000 M-1 cm-1) can be sensitively measured spectroscopically, the reaction of organic isothiocyanates with 1,2-benzenedithiol has been developed for analytical purposes. All aliphatic and aromatic isothiocyanates tested (except tert-butyl and other tertiary isothiocyanates) reacted quantitatively with an excess of 1,2 benzenedithiol. Thiocyanates, cyanates, isocyanates, cyanides, or related compounds did not interfere with this reaction under assay conditions. The method can be used to measure 1 nmol or less of pure isothiocyanates or isothiocyanates in crude mixtures. It can also be used to measure isothiocyanates in chromatographic fractions obtained from plant extracts and for the assay of the rate of cleavage of glucosinolates by myrosinase (thioglucoside glucohydrolase; EC 3.2.3.1). PMID- 1443547 TI - An electrophoresis-based assay for glycosyltransferase activity. AB - Polyacrylamide gel electrophoresis (PAGE) and capillary zone electrophoresis (CZE) were used to measure the activity of glycosyltransferases. Acceptor molecules were prepared by reductive amination of the monopotassium 7-amino-1,3 naphthalenedisulfonic acid (AGA) Schiff base with sugars. The resulting sugar conjugates were purified by gradient PAGE and recovered using semidry electrotransfer into a positively charged nylon membrane. The beta(1--- 4)galactosyltransferase was shown, by PAGE analysis, to transfer a beta galactosyl residue to the AGA conjugate of beta-D-GlcNAc-(1----4)-beta-D-GlcNAc (1----4)-D-GlcNAc (compound 4). Similarly, alpha(1----2)fucosyltransferase isolated from porcine submaxillary glands was shown to transfer fucose from GDP fucose to the AGA conjugate of beta-D-Gal-(1----4)-beta-D-GlcNAc-(1----6)-D-Gal (compound 5). This conjugate (compound 5) was also an acceptor for the alpha(1--- 3/4)fucosyltransferase partially purified from human milk. The latter reaction was followed by both gradient PAGE and CZE, having sensitivities of 200 pmol and 80 fmol, respectively. PMID- 1443548 TI - High-performance capillary electrophoresis of glycoproteins: the use of modifiers of electroosmotic flow for analysis of microheterogeneity. AB - High-performance capillary electrophoresis (HPCE) is rapidly gaining acceptance as an analytical tool for the study of biological macromolecules. In the present study, the utility of HPCE for separation of glycoproteins is highlighted using a pure ovalbumin preparation. Ovalbumin, the 43-kDa glycoprotein of avian egg white, is known to be heterogeneous in nature with at least nine different carbohydrate structures having been identified on the single Asn residue. HPCE separation in an 87-cm capillary containing borate buffer and 1 mM putrescine resolves five major protein peaks in less than 30 min under nondenaturing conditions. This effect appears to be specific to glycoproteins since analysis of the nonglycosylated protein carbonic anhydrase under the same conditions showed no enhanced separation. The sodium borate buffer is proposed to play a key role in the separation by preferentially complexing with the diols of specific carbohydrate moieties on ovalbumin. Addition of putrescine enhances resolution by slowing bulk flow through the capillary and allowing electrophoretic separation of what is deduced to be closely related glycoforms of ovalbumin. Dephosphorylation of the ovalbumin with either calf intestinal alkaline phosphatase or potato acid phosphatase results in a shift of all peaks to a more rapid migration time and is consistent with a loss of negative charge. This suggests that all major ovalbumin isoforms are phosphorylated to the same degree and that heterology among ovalbumin isoforms resides solely in the carbohydrate structure. The enhanced resolution obtained with the employment of longer capillaries and modifiers of endo-osmotic flow was not restricted to ovalbumin since partial resolution of pepsin isoforms was observed under the same conditions. PMID- 1443549 TI - Detection of receptor-ligand interactions using surface plasmon resonance: model studies employing the HIV-1 gp120/CD4 interaction. AB - Surface plasmon resonance (SPR), a label-free, real time optical detection principle, has been investigated for its potential to detect and quantitate macromolecular ligand-ligate interactions. As model systems, the interactions of the HIV-1 envelope glycoprotein, gp120, and the monoclonal antibody L-71, with a soluble form of the T-cell receptor CD4 (sCD4), were investigated. In an effort to demonstrate potential analytical applications of this technology, operational characteristics of the SPR instrumentation (BIAcore, Pharmacia) including stability of the sensing surface and reproducibility in the measurement of such macromolecular interactions were investigated. In addition, the ability to detect and quantitate sCD4 directly from unfractionated cell culture supernatants, such as Streptomyces lividans, was investigated. The results demonstrate that SPR has potential in quantitating macromolecular interactions in both purified and crude samples and that the reproducibility in, and sensitivity of, such determinations is comparable to other techniques. PMID- 1443550 TI - Immobilization chemistries suitable for use in the BIAcore surface plasmon resonance detector. AB - Surface plasmon resonance detectors, such as the BIAcore instrument produced by Pharmacia, show promise for the detection and quantitation of macromolecular interactions in a label-free mode. Such detectors rely on the covalent immobilization of one of the interacting species onto the sensing surface. To date, the only published chemistry for this purpose is reaction of primary amino containing ligands with an N-hydroxysuccinimide (NHS) ester-activated surface. In an effort to increase the versatility of the BIAcore with respect to immobilizing ligands, we undertook an investigation of activation chemistries compatible with this system. Using readily available reagents, we demonstrated that the carboxylated dextran-coated sensing surface could be easily converted to functions other than NHS-esters, including amine-activated, hydrazine-activated, and sulfhydryl-activated surfaces. In addition, use was made of the streptavidin/biotin interaction to probe chemical modifications of the sensing surface, by employing specifically modified biotin derivatives. PMID- 1443551 TI - High-performance liquid chromatographic separation with electrochemical detection of amino acids focusing on neurochemical application. AB - Twenty-three amino acids and dipeptides, including compounds of neurochemical interest, are measured by high-performance liquid chromatography using electrochemical detection after precolumn derivatization with o phthalaldehyde/beta-mercaptoethanol. The method uses a multistep polarity gradient system and the entire separation is performed in less than 23 min of analysis. The minimum detectable quantity was 0.66 pmol injected, corresponding to 50 nM concentration in the sample; the response was linear in the tested range of 1.33-1333 pmol (0.1-100 microM). Relative standard deviations ranged from 0.75 to 6.089% for area measurements (mean, 2.33) and from 0.209 to 0.779% for retention times (mean, 0.546). Examples of application of the method to analysis of biological samples such as rat brain homogenate and human cerebrospinal fluid are shown. PMID- 1443552 TI - Same-day batch measurement of glycine betaine, carnitine, and other betaines in biological material. AB - Glycine betaine, carnitine, carnitine esters, butyrobetaine, and proline betaine (stachydrine) concentrations in biological materials can be reliably measured in 100-microliters samples, with a detection limit below 1 mumol/liter. The procedure is suitable for batches of more than 30 specimens and it is possible to obtain a single result within 2 h. The betaines are extracted into an acetonitrile:methanol mixture, dried with anhydrous disodium hydrogen phosphate containing argentous oxide. The 4-bromophenacyl ester derivatives are formed using 4-bromophenacyl triflate as reagent, in the presence of solid magnesium oxide as base. The derivatives are separated by high-performance chromatography on a silica column, in a mixed partition and ion-exchange mode. PMID- 1443553 TI - Analysis of individual-site binding data. AB - Individual-site isotherms add experimental data which may allow for a more detailed definition of the parameters in a system with interacting binding sites. Individual-site isotherms accomplish the following: (A) In general, they define little more than the total or combined isotherm except to reveal the existence of different sites. (B) Under the limiting conditions of symmetrical interactions in two site systems they define: (1) the ratio of the unperturbed or intrinsic binding constants rather than their actual values, (2) the unperturbed shape of the total isotherm, that is, the shape of the total isotherm if there were no ligand dependent interactions between the sites, and (3) the perturbation of the shape of the total isotherm derived from interactions between the sites. (C) They do not define the nature of the interactions; that is, they do not resolve the free energies of the interactions between the sites. (D) When some assumptions about the nature of the interactions are made they may aid in defining some free energies of interaction between the sites. PMID- 1443554 TI - A method for determination of N-glycosylation sites in glycoproteins by collision induced dissociation analysis in fast atom bombardment mass spectrometry: identification of the positions of carbohydrate-linked asparagine in recombinant alpha-amylase by treatment with peptide-N-glycosidase F in 18O-labeled water. AB - Previously, a combined use of fast atom bombardment (FAB) mass spectrometry and peptide N-glycosidase F, an enzyme that cleaves the beta-aspartylglycosylamine linkage of Asn-linked carbohydrates, was successfully applied to identification of N-glycosylation sites in a glycoprotein with the known or DNA-derived sequence (S. A. Carr and G. D. Roberts, 1986, Anal. Biochem. 157, 396-406). Here, we extended the method for easier identification of N-glycosylation sites in a glycoprotein even with unknown sequence. The glycoprotein is digested with peptide-N-glycosidase F in buffer containing 40 at% H2 18O, to yield a deglycosylated protein whose carbohydrate-linked Asn residues are converted to Asp partly labeled with 18O at their beta-carboxyl group during this digestion. The deglycosylated protein is further digested with proteolytic enzymes in an appropriate buffer prepared with normal water, and then peptides are separated on a reversed-phase column by HPLC. Peptides in which carbohydrate-linked Asn has been converted to Asp show a pair of signals ([M + 1]+ and [M + 3]+) in FAB mass spectra due to the partial incorporation of 18O into the beta-carboxyl groups of Asp residues, while the other peptides show normal isotopic ion distributions. Thus, both formally N-glycosylated peptides and, using collision-induced dissociation analysis, N-glycosylation sites can be identified. The application of the present method to the determination of N-glycosylation sites in a recombinant glycoprotein, Bacillus licheniformis alpha-amylase, is described. PMID- 1443555 TI - A mass spectrometric method for measuring glycerol levels and enrichments in plasma using 13C and 2H stable isotopic tracers. AB - The stable isotope tracer [1,1,2,3,3,-2H5]glycerol has been commonly used as a tracer to measure glycerol kinetics and lipolysis in vivo. The method for measuring samples using the trimethylsilyl derivative and electron impact gas chromatograph-mass spectrometry retains only three of the five deuteriums, resulting in the possibility of incorrectly identifying the whole glycerol tracer molecule. This reports preparation of glycerol as the heptafluorobutyrl derivative and measurement by negative ion chemical ionization gas chromatography mass spectrometry to produce a derivative with an intense molecular ion that retains all five deuterium labels. Thus the heptafluorobutyrl derivative analyzed by negative ion mass spectrometry overcomes the problems associated with fragmentation and loss of the isotopic label. Glycerol concentration using a labeled internal standard can be determined in plasma with a precision of 3%. Nanomole amounts of glycerol can be analyzed for 13C or 2H enrichments with a precision of +/- 0.14 mol% excess isotope. This simple, sensitive method for measuring glycerol levels and stable isotopic enrichment in plasma uses a simple extraction procedure and requires a minimal volume of plasma (less than 300 microliters). PMID- 1443556 TI - Analysis of reactive carbonyls in the expired air of transgenic mice. AB - Methods for the determination of trace levels of volatile carbonyl compounds in air expired from mice were developed and validated. Tumor bearing transgenic mice or nontransgenic control mice were placed into a glass chamber through which air was passed continuously at 90 ml/min for 1 h. The effluent gas stream was bubbled into an aqueous cysteamine solution or an aqueous methylhydrazine solution. Formaldehyde, acetaldehyde, and acetone in expired air were derivatized to thiazolidine with cysteamine and malonaldehyde was derivatized to 1-methyl-2 pyrazole with methylhydrazine. The derivatized compounds were analyzed by capillary gas chromatography with flame photometric or nitrogen-phosphorous specific detection. The lowest level quantitated was 4 micrograms/ml thiazolidine, equivalent to 1.35 micrograms/ml formaldehyde. Formaldehyde was recovered at a level of 1356 +/- 234 nmol/kg0.75 (mean +/- SD) from mice with tumors and 898 +/- 97 nmol/kg0.75 from mice without tumors, suggesting that tumor bearing transgenic mice expired significantly more formaldehyde than did tumor free controls. Amounts of expired acetaldehyde and acetone were not different among mice. Malonaldehyde was not detected in either group of mice. PMID- 1443557 TI - Efficient precipitation and accurate quantitation of detergent-solubilized membrane proteins. AB - The protein assay method of I. Polacheck and E. Cabib (Anal. Biochem. 117, 311 314, 1981) has been modified to provide a general method for quantitating protein samples in the presence of detergents. Dilute detergent-solubilized membrane proteins, by using ribonucleic acid as a carrier, have been efficiently precipitated here by trichloroacetic acid (TCA) in the presence of sodium dodecyl sulfate (SDS). Washing the pellets once with TCA solution has removed most of the reagents present in the original sample. The washed sample could then be quantitated by the Lowry method (O. J. Lowry, N. J. Rosebrough, A. L. Farr, and R. J. Randall, J. Biol. Chem. 193, 265-275, 1951). This procedure could be used to assay protein solutions of a concentration as low as 5 micrograms/ml in the presence of the following reagents: Triton X-100, Triton X-114, Tween 20, N octylglucoside, deoxycholate, cholate, Thesit, octanoyl-N-methylglucamide, isotridecylpoly (ethyleneglycoether)n, Nonidet P-40, glucose, methyl-D glucopyranoside, methyl-D-mannopyranoside, N-acetyl-glucosamine, Mn2+, Ca2+, Mg2+, and many buffer reagents. Proteins solubilized from porcine brain myelin sheath and synaptic plasma membranes were quantitated by amino acid analysis and by the TCA/SDS precipitation method described here. The resultant protein concentrations were almost identical. The results have suggested this TCA/SDS precipitation method to be useful for quantitating dilute protein samples containing high concentrations of detergents and other reagents commonly employed in studying membrane proteins. PMID- 1443559 TI - A polymerase chain reaction-based method for isolation of gene-specific sequences from the interferon-alpha gene cluster. AB - The interferon-alpha gene is a gene family of over 20 distinct genes having 80 95% homology with one another at a nucleotide level. Because of the high homology in the gene cluster, the available interferon-alpha gene probes can hybridize to multiple bands of different size on Southern blot analysis of restricted human genomic DNA. We used the polymerase chain reaction with the primers synthesized from Alu repetitive sequence and the conserved sequences of the interferon-alpha gene cluster to generate specific probes for individual interferon-alpha genes. The amplification products were subcloned into a plasmid vector and analyzed by DNA sequencing and Southern blotting of the restricted human placental DNA. One clone, which derived from interferon-alpha 14 gene, produced a single 5.2-kb band in Southern blots of the HindIII-restricted human placental DNA. This stands in contrast to the 10 bands of different size that were detected with a cDNA for the interferon-alpha I' gene. Our results indicate that a polymerase chain reaction based method can be used to isolate gene-specific sequences from the interferon alpha gene cluster. Since a variety of human cancers has been found to have the complete or partial deletion of the interferon-alpha gene cluster, the gene specific probe generated by this method may aid in determining the breakpoints in the vicinity of the gene cluster. PMID- 1443558 TI - Selective 5' modification of T7 RNA polymerase transcripts. AB - We have developed two methods for selective 5' modification of RNAs generated by enzymatic synthesis using T7 RNA polymerase. The first method involves a two-step procedure. Transcription reactions are performed under standard conditions except that GTP is replaced by GTP gamma S. Since the polymerase initiates transcription with GTP, every transcript contains a 5' gamma-thiophosphate group which is modified with the thiol-specific reagent of choice (e.g., iodoacetyl dansyl derivative) in the second step. In an alternative method, transcription and modification reactions are carried out in a single step, using a mixture of dansylated GTP and GTP. Under the appropriate conditions, dansylated GTP effectively competes with GTP in the initiation reaction but does not substantially inhibit the elongation reaction. Yields of fluorescent 64-mer RNA ranging from 30 to 70% of the total transcription product have been obtained using these methods in combination with HPLC purification. This approach is amenable to large scale synthesis reactions and can be used to produce a wide variety of 5'-modified RNAs of virtually any size for structural or functional studies. PMID- 1443560 TI - A strategy for generating monoclonal antibodies against recombinant baculovirus produced proteins: application to the Bcl-2 oncoprotein. AB - A strategy is described for production of monoclonal antibodies against recombinant proteins that are produced using the baculovirus expression system and that requires no prior purification of the protein of interest. Crude lysates prepared from cultured Sf9 insect cells infected with recombinant or control baculoviruses are absorbed to nitrocellulose filters and used in a dot immunobinding assay for screening hybridomas. The monoclonal antibody-producing hybridomas are derived by immunization of mice with a synthetic peptide corresponding to a hydrophilic region in the recombinant protein of interest. By using the baculovirus-produced recombinant protein as the screening antigen and by comparing antibody binding to filters containing control Sf9 lysates, hybridomas are identified that produce monoclonal antibodies with specific reactivity for the recombinant protein of interest and that can then subsequently be used to assist in the large-scale purification of the recombinant protein from baculovirus-infected cells. We applied this method to recombinant 26-kDa human Bcl-2 (B-cell lymphoma/leukemia-2), an integral membrane oncoprotein that regulates programmed cell death ("apoptosis") in hematolymphoid cells through unknown mechanisms. Two mouse monoclonal antibodies were produced that specifically bound the recombinant Bcl-2 baculoprotein in both solution and solid phase assays. PMID- 1443561 TI - The use of streptavidin-biotinylglycans as a tool for characterization of oligosaccharide-binding specificity of lectin. AB - A new rapid and sensitive method for characterizing lectin specificity using streptavidin-biotinylglycans as a tool is presented. This assay is analogous to enzyme immunoassay and takes advantage of the strong, irreversible adsorption of streptavidin to the wells of the chambers of titer plates. A series of streptavidin-biotinylglycans was first coated on a microtiter plate, and then one of six lectins, concanavalin A, wheat germ agglutinin, Phaseolus vulgaris (red kidney bean) erythro-agglutinin, Lens culinaris (lentil) agglutinin, Datura stramoniun agglutinin, or Sambucus nigra (elderberry bark) agglutinin coupled to horseradish peroxidase, was added. After incubation and thorough washing, only the lectin bound to a complementary glycan remained and could be detected and quantified by the peroxidase reaction. It was established that the lectins retained their oligosaccharide-binding specificities after coupling to the peroxidase, that the binding was inhibited by addition of the corresponding sugar inhibitors, and that the color intensity produced by the enzyme reaction is proportional to the amount of lectin-peroxidase bound to biotinylglycan complexed with streptavidin immobilized on the plate. As an example, it was found that the peroxidase-D. stramoniun agglutinin conjugate strongly bound biotinylglycans, GlcNAc3-Man5-R, GalGlcNAc3Man5-R, and GlcNAc3-4Man3-R (R = GlcNAc2-[6 (biotinamido)hexanoyl]-Asn). As little as 10 pmol/ml of lectin was detected. With the growing availability of biotinylglycans, the method should represent a reliable and simple procedure for screening lectin-oligosaccharide recognition qualitatively and quantitatively. PMID- 1443562 TI - Noncolorimetric measurement of cell activity in three-dimensional histoculture using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide: the pixel image analysis of formazan crystals. AB - We describe a novel system for measuring the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) reduction in three-dimensional histoculture which is no longer dependent on colorimetric determination of extracted formazan, but rather is based on a pixel image analysis of formazan crystals, and which allows intratumor heterogeneity to be taken into account. The MTT test is based on the enzymatic reduction of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl) 2,5-dipheniltetrazolium bromide to formazan crystals by living, metabolically active cells, but not in dead cells. The reaction was carried out in situ in six well plates on gel-supported histocultured human tumors. After a 24-h incubation with different drugs the tumors were incubated with a solution of MTT. Frozen sections of the tumor pieces were made and the slides were then stained with a propidium iodide solution, whose fluorescence is proportional to the number of cells present. We demonstrate here that the formazan crystals, formed by MTT reduction, reflect polarized light and that this can be quantified by using an image analysis system based on bright-pixel quantitation directly on a frozen section of the original tissue. Combined with the use of the fluorescent dye propidium iodide, also measured by pixel analysis, we can express a ratio between the total amount of MTT reduction and the total number of cells present in the specimen that expresses the effect of drugs on the histocultured tumors. Since histology is well maintained in histoculture it is possible to take into account the heterogeneity present in the tumor with regard to drug response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443563 TI - An in vivo assay for measuring the recombination potential between DNA sequences in mammalian cells. AB - Mammalian intermolecular recombination vectors that place the recombination junction within the intron of a selectable marker gene are presented. Many of the previously reported recombination assays require that recombination occur homologously and that they occur within the coding region of the selectable marker. This vector system involves the use of a human thymidine kinase (tk) minigene and measures the recombination frequency between any chosen DNA sequences, in mammalian thymidine kinase negative cells. The tk minigene is divided into a 5' vector and a 3' vector. In the 5' vector, the DNA sequence of interest is inserted in the proximal portion of tk intron 2. In the 3' vector, the DNA sequence of interest is inserted in the intron sequence between the proteolipid protein exon 2 and tk exons 3-7. Recombination through the DNA sequences of interest, either homologous or illegitimate, will reconstruct a functional tk minigene. The recombination junction is spliced out of the transcribed mRNA and thymidine kinase positive cells can be selected in hypoxanthine-aminopterin-thymidine medium. We have tested these vectors to measure the recombination potential of two Alu repetitive sequences (BLUR 8 and BLUR 11) against a control DNA sequence. BLUR 8 and BLUR 11 do not seem to recombine at a significantly higher frequency over that of the control DNA sequence. These recombination vectors display similar sensitivity to previous recombination systems, but allow tremendous flexibility in the choice of potentially recombinogenic sequences. PMID- 1443564 TI - A reverse-phase HPLC assay for measuring the interaction of polyene macrolide antifungal agents with sterols. AB - A quick and simple affinity chromatography method for gauging the interaction of polyene antifungal agents with sterols has been developed. The required affinity columns are prepared from a standard C-18 reverse-phase HPLC column by injecting a measured quantity of sterol under conditions where it is completely retained. After the assay, the sterol is eluted with a less polar solvent and the column reused. By comparing the elution volume of a polyene injected onto the sterol free column (Ve) with that of the polyene injected onto the sterol-doped column (V), an association constant (Ka) for the polyene-sterol complex was determined. Association constants of different amphotericin B-sterol and pimaricin-sterol complexes were determined and correlated with the polyene's ability to induce membrane permeability and its antifungal properties. This procedure provides a new tool for screening polyene macrolides for antifungal therapy. PMID- 1443565 TI - Quantitative and qualitative analysis of amplified DNA sequences by a competitive hybridization assay. AB - The presence of allelic sequence variations in DNA fragments can be easily detected by measuring the extent of DNA strand exchange between test double stranded PCR products (target) and labeled standard double-stranded PCR products (probe). Under selected hybridization conditions, sequences identical to the probe decreased the formation of double-labeled hybrid, whereas differing sequences were not efficient enough to compete with the regeneration of the probe. A single base substitution in the target DNA increased the percentage of remaining double-labeled probe. A general procedure involving denaturation and hybridization in solution under different temperature conditions or using different probes enabled sequence identification. The degree of regeneration of double-labeled probe was determined using a bioluminescent assay. We evaluated the specificity of this method with two probes (108 and 131 bp) and several targets with different base substitutions. PMID- 1443566 TI - An in vitro method for radiolabeling proteins with 35S. AB - The radiolytic decomposition products of [35S]-methionine have been used to radiolabel proteins in vitro. The process occurs in a time-, temperature-, and pH dependent manner. Maximum labeling of bovine serum albumin occurs after a 24 h incubation at 37 degrees C and pH 8.5. Once incorporated, the radiolabel cannot be removed by extended incubation at various temperatures, multiple freeze/thaw cycles, or boiling, indicating that the 35S moiety is covalently attached to the protein. A wide variety of proteins have been radiolabeled. The method is simple to perform and yields radiolabeled proteins of high specific activity. PMID- 1443567 TI - A method for [3H]mannose labeling of Asn-linked oligosaccharides on recombinant glycoproteins synthesized in Xenopus oocytes. AB - We have developed an efficient method for labeling the Asn-linked oligosaccharides of recombinant glycoproteins synthesized in Xenopus laevis oocytes. By coinjecting GDP-[3,4-(3)H]mannose with mRNA for human cathepsin D, it was possible to incorporate as much as 1800 cpm per oocyte into each of the two Asn-linked oligosaccharides of this glycoprotein. Overall, about 50% of the microinjected GDP-[3,4-(3)H]mannose was incorporated into Asn-linked oligosaccharides, a 10-fold greater value than that obtained when [2-(3)H]mannose was microinjected. Less than 10% of the injected GDP-[3,4-(3)H]mannose was metabolized to water or converted to amino acids. This technique should facilitate studies of Asn-linked oligosaccharide biosynthesis, processing, and structure in recombinant proteins synthesized in Xenopus oocytes. PMID- 1443568 TI - Two-dimensional mapping of N-glycosidically linked asialo-oligosaccharides from glycoproteins as reductively pyridylaminated derivatives using dual separation modes of high-performance capillary electrophoresis. AB - N-Glycosidically linked oligosaccharides were released from glycoproteins by digestion with trypsin followed by hydrazinolysis and subsequently re-N acetylated and reductively pyridylaminated. Derivatives of sialic acid-containing oligosaccharides were further desialylated with neuraminidase. The final derivatives of asialo-oligosaccharides were analyzed by capillary zone electrophoresis in two carriers, an acidic phosphate buffer and an alkaline borate buffer. The former carrier allowed direct zone electrophoresis as cationic immonium ions, accordingly size-dependent separation, whereas the latter realized indirect electrophoresis as anionic borate complexes, i.e., separation based on the structural variation in outermost monosaccharide residues. Two-dimensional plots of relative mobilities of the derivatives in these dual separation modes to reductively pyridylaminated glucose provided a good tool for identification of oligosaccharides. PMID- 1443569 TI - Electroporation-mediated gene transfer efficiency is reduced by linear plasmid carrier DNAs. AB - Carrier DNA has generally been found to stimulate DNA-mediated gene transfer of Chinese hamster ovary (CHO) cells by calcium phosphate coprecipitation. In studies employing electroporation, however, we observed that linear plasmid DNA was inhibitory to the transfection of CHO cells. This unexpected result prompted us to explore the effects of various types and forms of plasmid, cosmid, and chromosomal DNAs on transfection efficiencies. Both carrier DNA form and type were found to influence transfection efficiencies. Circular and linear forms of plasmid carrier DNA had opposite effects: circular plasmids increased and linear plasmids decreased transfection efficiencies. These effects were independent of homology with the selected plasmid and are probably independent of homologous recombination mechanisms. Bacterial genomic DNA failed to stimulate transfection, while calf thymus and cosmid DNA consisting primarily of human sequences stimulated transfection significantly. Our results have importance for plasmid based experiments in mammalian cells such as those involving the induction of interplasmid homologous recombination. PMID- 1443570 TI - Analytical methods for identifying and quantitating deamidated sialic acid (2 keto-3-deoxy-D-glycero-D-galactonononic acid) and alpha 2----8-linked poly(oligo)nonulosonate residues in glycoconjugates. AB - In 1986 we reported the natural occurrence of deaminated neuraminic acid (2-keto 3-deoxy-D-glycero-D-galactonononic acid, KDN) in fish egg glycoprotein. Subsequently, we have shown that many types of sialic acid as well as KDN occur in polymeric chains, poly(oligo)-Sia and poly(oligo)KDN in nature. In this study we demonstrate that the conventional colorimetric and gas-liquid chromatographic methods used in the analysis of sialic acid can be applied to analysis of these new nonulosonate and poly(oligo)nonulosonates. We report that the thiobarbituric acid reaction can be used to analyze both free and bound KDN, but gives lower extinction values when applied to poly(oligo)KDN without prior hydrolysis. Further, the published hydrolytic and/or methanolytic procedures are suitable to release the terminal sialic acid residues, but are not appropriate for quantitative release of the nonulosonic acids from poly(oligo)nonulosonates. A new gas-liquid chromatographic procedure for the identification-quantitation of nonulosonates in poly(oligo)meric forms is described. PMID- 1443571 TI - Determination of lectin characteristics by a novel agglutination technique. AB - A technique generally applicable for the determination of lectin characteristics is described. A sensitive light transmission/scattering method was adapted for the determination of lectin levels and lectin activity. Applying this procedure Geodia cydonium lectin-mediated agglutination was studied in an agglutimeter device using erythrocytes and even T-lymphocytes. In the Geodia lectin/T lymphocyte system chosen, (i) a lectin concentration as low as 0.57 micrograms/ml could be measured accurately, (ii) the observed cell agglutination velocity constant with a maximal value of 0.75 min-1 was calculated, and (iii) the size of the agglutinates at a given lectin concentration and time period was estimated. The Geodia lectin activity was determined in parallel also in the erythrocyte system. Here, compared to the lectin/T-lymphocyte system the agglutination efficiency of the Geodia lectin-mediated agglutination was more than 10-fold higher and the lowest detectable lectin concentration was 0.06 micrograms/ml. Compared to the hemagglutination assay the lectin/erythrocyte system turns out to be more sensitive and to give much more information on agglutination behavior; this conclusion is supported by additional data using a second lectin isolated from Pellina semitubulosa. The superiority of the agglutination method described here over other known methods must be seen in its accuracy; moreover more lectin characteristics can be determined. PMID- 1443572 TI - An unexpected side reaction in the guaiacol assay for peroxidase. AB - In routine guaiacol assays for thyroid peroxidase and lactoperoxidase employing a newly purchased bottle of guaiacol from Aldrich Chemical Co., we were surprised to find the formation of a blue color instead of the expected amber color classically associated with this assay. This was observed also with horseradish, myelo-, and cytochrome c peroxidase. The blue color (Amax approximately 650 nm) was not formed with guaiacol reagents obtained from two other chemical companies, nor was it seen with a bottle of old Aldrich guaiacol that had been in use in the laboratory for more than 10 years. In the present investigation we provide evidence that formation of the blue color is closely associated with the presence of a low concentration of catechol (approximately 0.5 mol%) in the new Aldrich guaiacol reagent. Catechol itself, even in much higher concentration, is a very weak donor for peroxidase, forming a light pink color. The blue color in Aldrich new guaiacol is not formed to the exclusion of 470-nm-absorbing product(s). Formation of the latter is, however, inhibited, and use of Aldrich new guaiacol for assay leads to low values for peroxidase activity. Other dihydroxyphenols (resorcinol and hydroquinone) do not mimic the action of catechol in formation of the blue color. Resorcinol is a very potent inhibitor of peroxidation of guaiacol. Possible schemes are proposed for formation of the products that may be associated with the amber and blue colors. PMID- 1443573 TI - Speciation of tissue and cellular iron with on-line detection by inductively coupled plasma-mass spectrometry. AB - Iron accumulating to excess in tissues of humans and animal models occurs mainly as complexes with transferrin, ferritin, other hemoproteins, and insoluble hemosiderin particles. To determine the distribution of Fe amongst these molecular species, we have used inductively coupled plasma-mass spectrometry as a means of on-line, isotope-specific detection for their liquid chromatographic separation. The stable isotope 57Fe is a suitable isotope for monitoring the Fe content of each fraction, and its availability at high isotopic enrichment makes it an attractive choice for tracer studies when the use of a radioisotope is undesirable, e.g., in human subjects. The detection system offers the advantages of high sensitivity (detection limits in the parts per billion range), a wide dynamic range (linearity of the calibration curve over several orders of magnitude), and on-line analysis facilitating real-time evaluation of the chromatographic separation, in addition to isotope-specific information. The Fe distributions in healthy rat livers, liver and heart tissue from Fe-loaded human subjects, and human hepatocyte cultures are reported. The ferritin:hemosiderin ratio in these samples is shown to be an indicator of the degree of Fe loading and correlates well with that determined by Zeeman-corrected electrothermal atomic absorption as an alternative means of detection. PMID- 1443574 TI - Spectrophotometric measurement of flavin-containing monooxygenase activity in freshly isolated rat hepatocytes and their cultures. AB - The determination of the mixed function flavin-containing monooxygenase activity in rat liver and in hepatocytes and their cultures by spectrophotometric measurement of the oxygenation of methimazole is complicated by an inhibition caused by some of the reagents used during this method. Optimal conditions were determined for measuring this enzyme activity in microsomal preparations of rat liver and its hepatocytes. Optimal flavin-containing monooxygenase activities were obtained for measurements performed in a 0.25 M N-[2-hydroxy-1,1 bis(hydroxymethyl)ethyl]glycine-EDTA buffer at pH 8.7 and at a methimazole concentration of 2 mM. Data are also presented which show that no interferences caused by either cytochrome P450-dependent enzymes or by the reduction of methimazole disulfide by glutathione have to be taken into account when determining methimazole oxygenation. Finally, the above assay was also used to study flavin-containing monooxygenase activity in primary monolayer cultures of hepatocytes for 6 days. PMID- 1443575 TI - Mutational analysis by a combined application of the multiple restriction fragment-single strand conformation polymorphism and the direct linear amplification DNA sequencing protocols. AB - We describe here an improved procedure for polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) for rapid mutational detection. To circumvent the restriction of having to analyze relatively short PCR fragments, restriction endonucleases were used to cleave a longer PCR product and the mixture of fragments was analyzed directly in SSCP gel electrophoresis. This multiple restriction fragment (MRF)-SSCP protocol was demonstrated by the detection of a 4-bp deletion in codons 41-42 and a point mutation in the IVS-2 sequence of the human beta-globin gene. The MRF-SSCP or the standard SSCP protocol was then combined with the linear amplification DNA sequencing (LADS) procedure for direct analysis of the PCR products without further purification for an exact characterization of the mutations detected. In the LADS analysis, homo- or heterozygosity of a mutation was easily distinguished by the appearance of a single- or double-lane band in the sequencing gel. The choice of isotope used and different labeling methods were compared and were found, in some cases, to produce SSCP patterns of different complexities. The combined MRF-SSCP/LADS protocol permits rapid mutational analysis of a large number of clinical samples using only very small amounts of materials and can easily be adopted for nonisotopic clinical applications. PMID- 1443576 TI - Assay for O6-alkylguanine-DNA-alkyltransferase using oligonucleotides containing O6-methylguanine in a BamHI recognition site as substrate. AB - Double-stranded oligonucleotides, 40 bases in length containing an O6 methylguanine in a BamHI restriction site, were developed as substrates for the determination of human O6-alkylguanine-DNA-alkyltransferase (AGT). The assay proved highly sensitive and quantitative. After incubation of the 5'-end-labeled oligonucleotides with cell homogenates of peripheral blood lymphocytes, the DNA was digested with BamHI. Cleavage with this restriction enzyme did not occur in the O6-methylguanine-containing oligonucleotide unless the fragment was repaired. The cleaved oligonucleotide was separated from the intact parent oligonucleotide by reverse-phase high-performance liquid chromatography. Calculation of the AGT content was achieved by integrating the radioactivity of the peak corresponding to the digested fragment, which is equal to the molar amount of repaired oligonucleotide and corresponds directly to the molar AGT content in the lymphocyte homogenate. PMID- 1443577 TI - Pineal and plasma melatonin as determined by high-performance liquid chromatography with electrochemical detection. AB - A rapid and sensitive method for the routine quantitative determination of melatonin in pineal and plasma is described. The assay used reversed-phase high performance liquid chromatography (RP-HPLC) separation combined with either amperometric (system A) or coulometric (system B) detection. The method gave satisfactory reproducibility and accuracy, and detection limits for melatonin were as low as 8.5 pg (system A) and 1 pg (system B). This high sensitivity, together with the short analysis time (less than 10 min), and the simplicity of sample procedure make the present RP-HPLC method suitable for a wide range of studies concerning melatonin measurements. Melatonin values obtained in this study from both rat pineal and human plasma agree with those reported previously, and clearly determined a circadian pattern. PMID- 1443578 TI - Detection of Clostridium botulinum toxin A using a fiber optic-based biosensor. AB - A rapid, sensitive, analytical method for the detection of Clostridium botulinum toxin has been developed. The fiber optic-based biosensor utilizes the evanescent wave of a tapered optical fiber for signal discrimination. A 50 mW argon-ion laser, which generates laser light at 514 nm, is used in conjunction with an optical fiber probe that is tapered at the distal end. Antibodies specific for C. botulinum are covalently attached to the surface of the tapered fiber. The principle of the system is a sandwich immunoassay using rhodamine-labeled polyclonal anti-toxin A immunoglobin G (IgG) antibodies for generation of the specific fluorescent signal. Various anti-toxin antibodies were immobilized to the fibers. Affinity-purified polyclonal horse anti-toxin A antibodies performed better than the IgG fraction from the same horse serum or than the monoclonal anti-toxin A antibody BA11-3. Botulinum toxin could be detected within a minute, at concentrations as low as 5 ng/ml. The reaction was highly specific and no response was observed against tetanus toxin. PMID- 1443579 TI - Reversible immobilization of antibodies on magnetic beads. AB - A streptavidin-biotin system was utilized to prepare an antibody-polyadenylic acid conjugate which was subsequently attached to commercially available magnetic beads, Dynabeads oligo(dT)25. Biotinylated polyadenylic acid was combined with streptavidin and the resulting polyadenylic acid-streptavidin was conjugated with an antibody-biotin derivative. The immobilized antibody-polyadenylic acid conjugate was separated from the reaction mixture by hybridization with complementary oligonucleotide immobilized on the surface of Dynabeads oligo(dT)25. The immobilized antibody-polyadenylic acid can be released from the carrier, utilizing low-ionic-strength buffers. The system is intended to be utilized in cell sorting, using immobilized antibodies against cell surface antigens. Dissociation of antibody-containing conjugate from magnetic beads is essential for the isolation of viable cells via positive cell sorting. PMID- 1443580 TI - Analysis of the biogenic amines in the central nervous system of the tobacco hornworm by high-performance liquid chromatography with 16-sensor electrochemical detection. AB - A method was developed to analyze biogenic amines in extracts of the central nervous system of the tobacco hornworm, Manduca sexta by high-performance liquid chromatography with 16-sensor electrochemical detection (n-EC-HPLC). The amines, precursors, and metabolites were separated in two dimensions. The first dimension involves separation based upon retention time by reversed-phase HPLC, while the second dimension involves separation based upon the characteristic oxidation potentials achieved by n-EC. Biogenic amine identification was based upon maximum oxidation potential and peak height ratios in addition to retention time. The improved resolving power of this method allows for a simplified sample preparation procedure and simultaneous determination of a wide range of compounds, including phenylethylamine, catecholamines, indoleamines, and some of their precursors and metabolites. PMID- 1443581 TI - Determination of nicotinamide phosphoribosyltransferase activity in human erythrocytes: high-performance liquid chromatography-linked method. AB - A radiochemical reverse-phase-high-performance liquid chromatography-linked method to measure the activity of nicotinamide phosphoribosyltransferase (EC 2.4.2.12) in crude lysates of human red blood cells is described. The apparent Km for nicotinamide was in the micromolar range, much lower than that described in human erythrocytes in the past. The enzyme activity in crude hemolysates was found to be extremely low (21 +/- 3.5 nmol x h-1 x g-1 Hb); nevertheless, the low Km for nicotinamide might account for the production of pyridine nucleotides reported by us for intact erythrocytes incubated at low, physiological concentrations of this substrate. PMID- 1443582 TI - Method for estimation of benzo[a]pyrene DNA adducts. AB - Polycyclic aromatic hydrocarbons, e.g., benzo[a]pyrene (B(a)P) are known carcinogens/mutagens. These compounds may be metabolized by the P450 mixed function monooxygenase to more nucleophilic compounds which may form adducts to the cellular macromolecules, e.g., DNA, RNA, and proteins. We have used synchronous fluorescence scanning for the assay of DNA adduct formation. In our earlier work with in vitro exposed human lymphocytes we estimated the adduct formation (femtomoles B(a)P per microgram DNA) to be higher than that estimated by other workers. We suggested that this difference may be related to the DNA isolation method used. In order to elucidate these differences we compared DNA adduct formation in human lymphocytes where DNA was isolated by the two different methods, i.e., using phenol extraction or the Gene Clean method. The data demonstrate that the phenol extraction procedure gives a yield of adducts per microgram DNA lower than that obtained by the Gene Clean method. The principle of the Gene Clean method for DNA isolation is protein denaturation by means of NaI followed by catching of DNA by absorption on silica particles. In contrast, the phenol extraction method is based upon phenol-mediated denaturation of proteins in the cell lysate leaving the hydrophilic nucleotides in the aqueous phase. However, during adduct formation more lipophilic adducts derived from DNA may redistribute between the aqueous phase and the phenol phase. In support of this theory we found higher adduct concentration per microgram DNA by the Gene Clean method 40 to 60 times than that found by the phenol method.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443583 TI - Effect of temperature on the spectral properties of coenzyme F420 and related compounds. AB - The uv-visible spectra of 7,8-didemethyl-8-hydroxy-5-deazaflavin-5' phosphoryllactyl glutamate (coenzyme F420), a naturally occurring 5-deazaflavin derivative, in three different buffers changed with a rise in temperature; the effect on the extinction coefficient at 420 nm (epsilon 420) was as follows: In phosphate-buffered solutions at pH less than 7.5, the epsilon 420 increased (at pH 5.0 for a temperature shift from 15 to 60 degrees C, delta epsilon 420 was +87%), but between pH 7.5 and 8, epsilon 420 changed very little. At pH greater than 8.0 in phosphate- or borate-buffered solutions, epsilon 420 decreased slightly. In morpholineethanesulfonic acid (Mes)-buffered F420 solutions at pH 5 and 5.5, epsilon 420 changed very little, whereas at pH 6-8, the epsilon 420 decreased. Absorbance of F420 at 401 nm in phosphate buffer at pH 5 to 9 was not significantly affected by temperature. Changes in epsilon 420 due to temperature change corresponded to changes in the pKa of 8-OH of the deazaflavin molecule; studies with adenylated F420 showed that the 8-OH of F420 was responsible for these changes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443584 TI - Interactions in affinity partition studied using fluorescence spectroscopy. AB - Fluorescence titration has been used to determine the binding constant and number of binding sites for the textile triazine dye Procion Yellow HE-3G to lactate dehydrogenase from rabbit muscle (E.C. 1.1.1.27). Triazine dye was either free in solution or attached to one of the polymer carriers, polyethylene glycol or dextran. Titrations were performed in solutions of buffer, dextran, and polyethylene glycol. Aqueous two-phase systems composed of polyethylene glycol and dextran were prepared and the binding constant and number of binding sites for ligand polyethylene glycol-Procion Yellow to lactate dehydrogenase were determined in both upper and lower phases of these systems. Affinity partition of lactate dehydrogenase in a PEG-dextran system was also performed using PEG Procion Yellow as ligand, and partition coefficients of lactate dehydrogenase showed good agreement with theoretical partition coefficients calculated from the binding constant and number of binding sites obtained from fluorescence titration. The advantage of using fluorescence titration to determine affinity of a polymer ligand for a protein is that measurement of binding strength can be made in the actual environment encountered by protein-ligand complex during the purification process. PMID- 1443585 TI - A comparison of substrates for quantifying the signal from a nonradiolabeled DNA probe. AB - A method for measuring the amount of a nonradiolabeled DNA probe using four detection substrates is described. In preliminary experiments, digoxygenin labeled DNA was bound to neutral, nylon membranes and detected with anti digoxygenin antibodies conjugated to alkaline phosphatase. Four substrates [4 nitrophenyl phosphate, 4-methylumbelliferyl phosphate, AttoPhos, and adamantyl 1, 2-dioxetane phosphate (AMPPD)] were assessed for use in a quantitative hybridization assay. Only AttoPhos and AMPPD were found to have detection limits in the low picogram range and to respond linearly to DNA concentrations ranging from 0 to 1250 pg. In subsequent experiments, a 200-bp DNA probe cloned from the marine bacterium Pseudomonas perfectomarina 23S rRNA gene was hybridized to P. perfectomarina genomic DNA and total RNA. The amount of hybridized probe was determined using AttoPhos. Finally, a digoxygenin-labeled oligonucleotide was probed against genomic DNA. Linearity with respect to DNA concentration was observed using both the 200-bp fragment and the oligonucleotide as probes with a final target detection limit of 166 fg. This study demonstrates the substrate AttoPhos can be used to quantify the amount of nonradiolabeled probe hybridized to target with sufficient sensitivity for very dilute samples, such as environmental samples. PMID- 1443586 TI - Synthesis of N,N-dilactitol ethylenediamine: a versatile spacer for attachment of residualizing labels to protein. PMID- 1443587 TI - Iron contamination in adenosine triphosphate: a warning. PMID- 1443588 TI - Measurement of the activity of individual respiratory chain complexes in isolated fibroblast mitochondria. PMID- 1443589 TI - Why, when, and how biochemists should use least squares. AB - One of the most commonly used methods for the analysis of experimental data in the biochemical literature is nonlinear least squares (regression). This group of methods are also commonly misused. The purpose of this article is to review the assumptions inherent in the use of least-squares techniques and how these assumptions govern the ways that least-squares techniques can and should be used. Since these assumptions pertain to the nature of the experimental data to be analyzed they also dictate many aspects of the data collection protocol. The examination of these assumptions includes a discussion of questions like: Why would a biochemist want to use nonlinear least-squares techniques? When is it appropriate for a biochemist to use nonlinear least-squares techniques? What confidence can be assigned to the results of a nonlinear least-squares analysis? PMID- 1443590 TI - Semipreparative isolation of individual cyanobacterial heterocyst-type glycolipids by reverse-phase high-performance liquid chromatography. AB - Procedures are described for the quantitative, semi-preparative isolation of individual cyanobacterial heterocyst-type glycolipids (HGs) by reverse-phase HPLC (RP-HPLC) and the modifications to conventional techniques necessary to prevent significant HG losses during sample preparation. Total lipids are obtained from cultures of nitrogen-fixing cyanobacteria by triplicate extraction with 200 packed-cell volumes of chloroform/methanol (1/1, v/v), filtered, and redissolved in chloroform for loading onto a short disposable column of acid-washed silica. After removal of neutral lipids, pigments, and the majority of monogalactosyldiacylglycerol with chloroform and chloroform/acetone, HGs are eluted along with other complex lipids in methanol. The complex lipids are then fractionated by TLC and the HGs isolated as two classes of differing mobilities. The individual components of each class are then resolved by isocratic elution with methanol/water (91/9, v/v) from a C18 RP-HPLC column with refractive index detection. Samples of up to approximately 1.0 mg lipid can be completely separated and the major components isolated in high purity from a single run. Structural studies on the major HG of Nostoc azollae show it to be the glycosylated hexacosane-1,3,25-triol found by others in Anabaena cylindrica. PMID- 1443591 TI - Separation and purification of dolichol and dolichyl phosphate by anion-exchange paper chromatography: application to cultured cells. AB - Dolichyl phosphate, dolichol C80-105 (dolichol 17:dihydroheptadecaprenol-dolichol 21:dihydrohexeicosaprenol), and dolichol C55 (dolichol 11:dihydroundecaprenol) were separated by anion-exchange paper chromatography. Squalene, sterols, phospholipids, anionic glycolipids, and glycerol did not migrate as dolichyl phosphate, dolichol C80-105, and dolichol C55 under our elution conditions. However, since the Rf of triglycerides was similar to that of dolichol C80-105, saponification, prior to chromatography, removed traces of triglycerides. Silica gel thin-layer chromatography (TLC) allowed the separation of dolichol C80-105 from dolichol C55, whereas dolichyl phosphate was eluted with other lipids. Incubation of spontaneously transformed cells derived from rat astrocytes primary cultures with [2-14C]acetate, saponification of the extracted lipids, and anion exchange paper chromatography revealed the presence of radioactive dolichyl phosphate and dolichol C80-105 (15 pmol/mg protein). Extraction of labeled dolichyl phosphate followed by acid phosphatase treatment and subsequent analysis on TLC confirmed the identity of dolichyl phosphate since all the radioactivity was associated with dolichol C55. Treatment of the transformed cells with 30 microM 7-ketocholesterol or 7 beta-hydroxycholesterol stimulated markedly (two- to threefold) the incorporation of [2-14C]-acetate in both dolichol C80-105 and dolichyl phosphate. These data demonstrate that anion-exchange paper chromatography is technically suitable for the separation and analysis of dolichol C55, dolichol C80-105, and dolichyl phosphate in cultured cells prelabeled with radioactive precursors. PMID- 1443592 TI - A method for specific analysis of free fatty acids in biological samples by capillary gas chromatography. AB - The present report describes a simple method to selectively extract free fatty acids and analyze them by capillary gas-liquid chromatography. The procedure is based on the use of fumed silicon dioxide. In the presence of plasma, this material induces a rapid rise in the viscosity of the mixture and presents the ability to trap large particles such as emulsified lipids and lipoproteins. Albumin-bound fatty acids are thus left in the aqueous media. We present applications of our procedure for the analysis of free fatty acids in 0.2 ml of plasma from rat or human. By comparison with the method utilizing thin-layer chromatography for the separation of fatty acids and gas chromatography analysis, the present method has been found to be reliable and simple. The recovery of linoleic acid was 92.1 +/- 8.2%, a value which is about twice better than that obtained with the procedure using thin-layer chromatography. In particular, long chain polyunsaturated fatty acids were better preserved. Our procedure does not require the use of organic solvents and its simplicity and reproducibility make it suitable for routine specific determination of the composition of free fatty acids in biological samples. PMID- 1443593 TI - A fluorometric assay for cholesterol reductase activity. AB - A fluorometric method for the assay of cholesterol reductase activity from pea leaves (Pisum sativum) is presented. This method is based on the decrease in relative fluorescence occurring as a result of the oxidation of NADH when cholesterol is reduced catalytically to coprostanol by cholesterol reductase. The reaction mixture consisted of micellar cholesterol, NADH, and cytosol of pea leaves in a phosphate buffer. After incubation for 1 h, the reaction mixture were diluted with 2-(N-cyclohexylamino)ethanesulfonic acid buffer (50 mM, pH 10.0) to an appropriate concentration for NADH quantification. The relative fluorescence was measured at an excitation wavelength of 360 nm and at an emission wavelength of 460 nm. This fluorometric method is relatively rapid, simple, and inexpensive. The results obtained show close correlation (R = 0.997) with those obtained by the more time-consuming and expensive radiometric method for assay of cholesterol reductase activity. Results suggest that the fluorometric method is useful for the accurate determination of cholesterol reductase activity in biological specimens. PMID- 1443594 TI - Identification of glycerophosphorylcholine in mussel ovarian extracts by two dimensional nuclear magnetic resonance. AB - The abundance of the "phosphodiester" peak in differentiating or proliferating tissues, including reproductive organs and tumors, warrants further investigations of its metabolic role(s), which would require a rigorous confirmation of its identity. The assignment of this peak to glycerophosphorylcholine in 31P NMR spectra of biological samples has been largely based on chemical shift, which can result in ambiguities. We employed a combination of two-dimensional 31P-1H heteronuclear shift correlation and 1H total correlation spectroscopies to trace the spin connectivities of glycerophosphorylcholine and thus to identify its structure directly from crude ovarian extracts of mussels without ambiguities and the need for extensive purification. This approach can be applied generally to the identification of molecules containing heteroatoms in crude tissue extracts. PMID- 1443595 TI - The quantitative analysis of endogenous folate catabolites in human urine. AB - In man folates are catabolized and excreted as inactive cleaved degradation products, a mixture of pteridines and p-aminobenzoylglutamate (pABGlu) or its acetamido derivative (apABGlu). The daily rate of excretion represents the inescapable use of the vitamin in metabolic activity and thus has implications for determining the recommended dietary allowance for the vitamin. Furthermore, the rate of catabolism has been suggested to rise during pregnancy and in certain disease states. A method is described for the quantitative extraction and assay of the folate catabolites pABGlu and apABGlu in human urine. Aliquots of 24-h urine collections are acidified and applied to columns of Dowex 50W cation exchange resin. The catabolites are selectively batch-eluted with increasing concentrations of HCl. The fraction containing pABGlu is diazotized and then applied to a C18 Sep Pak column for further purification and concentration. The fraction containing apABGlu was deacetylated and reapplied to the Dowex column and then treated identically to the pABGlu fraction. The methanolic concentrates of both extracts were evaporated to dryness and reconstituted with water and pABGlu was regenerated by reductive cleavage of the diazotized material with Zn/HCl. The extracts of the two catabolites were separated by reverse-phase HPLC using a Radial Pak C18 column. Recovery of isolated material was monitored by the addition of high specific activity tritiated labels of both compounds added as internal standards to all urine aliquots prior to purification and analysis. PMID- 1443596 TI - A coupled assay for UDP-GlcNAc:Gal beta 1-3GalNAc-R beta 1,6-N acetylglucosaminyltransferase (GlcNAc to GalNAc). AB - UDP-GlcNAc:Gal beta 1-3GalNAc-R beta 1,6-N-acetylglucosaminyltransferase (GlcNAc to GalNAc) (i.e., core 2 GlcNAc-T) is a developmentally regulated enzyme of the O linked oligosaccharide biosynthesis pathway. We have developed a coupled-enzyme assay for core 2 GlcNAc-T that is approximately 100 times more sensitive than the standard assay using UDP-[3H]GlcNAc as a sugar donor. Core 2 GlcNAc-T reactions were performed using unlabeled UDP-GlcNAc donor and Gal beta 1-3GalNAc alpha paranitrophenyl (pNp) as acceptor. The product, Gal beta 1-3(GlcNAc beta 1 6)GalNAc alpha-pNp was then further reacted with purified bovine beta 1-4Gal-T and UDP-[3H]Gal to produce Gal beta 1-3([3H]Gal beta 1-4GlcNAc beta 1-6) GalNAc alpha-pNp, which was separated on an Ultrahydrogel HPLC column. Approximately 10% of the available GlcNAc-terminating acceptor was substituted in the Gal-T reaction, allowing 1 pmol of product to be readily detected. The increased sensitivity of the coupled assay should facilitate studies of core 2 GlcNAc-T activity where material is limiting or specific activity is low. PMID- 1443597 TI - A nonradioactive biochemical characterization of membrane proteins using enhanced chemiluminescence. AB - Here we demonstrate a nonradioactive immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) technique which replaces the standard practice of isotopic protein labeling by iodination or metabolic tagging in the analysis of membrane proteins. The technique has proved extremely valuable in the biochemical analysis of small quantities of frozen, pathological tissue. Membranes were prepared from Dx3 (a human melanoma cell line), C6 (a rat glial cell line), and osteoclastoma (a human giant cell tumor of bone). The membranes were labeled with biotin and immunoprecipitated with a variety of antibodies to the vitronectin receptor (VNR). The VNR proteins were resolved by SDS-PAGE and immunoblotted onto nitrocellulose paper. The biotinylated protein was visualized using streptavidin horseradish peroxidase and enhanced chemiluminescence (ECL). Film exposures ranged from 15 min to 16 h. Good visualization of the VNR, yielding the typical heterodimeric receptor of 90 and 150 kDa, was given. Signals generated were high and background noise low with a 30-min film exposure. An overnight exposure increased the detection of weaker bands. In conclusion, biotinylation of membrane proteins proved a satisfactory label for immunoprecipitation and SDS-PAGE analysis. The ECL development stage was extremely flexible with visualization of strong and weak signals. The method has several advantages over a conventional radioactive immunoprecipitation in that it is relatively inexpensive, simple, quick and nonhazardous. PMID- 1443598 TI - Quantitative mapping of the N-linked sialyloligosaccharides of recombinant erythropoietin: combination of direct high-performance anion-exchange chromatography and 2-aminopyridine derivatization. AB - A rapid quantitative analysis of the sialylated N-linked oligosaccharides of recombinant erythropoietin (EPO) expressed in Chinese hamster ovary (CHO) cells has been developed. The procedure utilizes a glycoamidase (glycopeptidase F) to release all of the N-linked oligosaccharides from the native glycoprotein, followed by direct chromatographic analysis using high-performance anion-exchange chromatography (HPAEC) with pulsed amperometric detection. The eight sialyloligosaccharides isolated from HPAEC were characterized by derivatizing with 2-aminopyridine followed by two-dimensional HPLC mapping of the pyridylaminated asialooligosaccharides (Tomiya et al., 1988, Anal. Biochem. 171, 73-90). Seven kinds of complex-type asialooligosaccharides were identified ranging from a biantennary structure to N-acetyllactosamine-extended tetraantennary structure. Approximately 3% of the terminal galactose residues of the oligosaccharides released from EPO were not sialylated whereas 97% contained an alpha(2-->3)-linked sialic acid. Quantitative oligosaccharide mapping of four different lots of EPO from CHO cells was performed to quantify the molar balance and distribution of the N-linked oligosaccharides. The sialyloligosaccharides were distributed with approximately 5% disialylated (single type), 20% trisialylated (six types), and 75% tetrasialylated (four types) oligosaccharides with an average molar recovery of 85% starting from 750 pmol of EPO. PMID- 1443599 TI - An ultrasensitive human immunodeficiency virus type 1 protease radioimmuno rate assay with a potential for monitoring blood levels of protease inhibitors in acquired immunodeficiency disease syndrome patients. AB - The angiotensin I-based peptide Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Glu Glu-Ser yields angiotensin I (Ang I) and Leu-Glu-Glu-Ser upon hydrolysis by the human immunodeficiency virus type 1 (HIV-1) protease, but not by human renin. N terminal sequencing of the reaction products showed that the HIV-1 protease cleaved exclusively at the Leu-Leu bond. The rate of Ang I formation can be measured by a radioimmunoassay, since the parent peptide has minimal cross reactivity in this assay. The rate of enzymatic hydrolysis is maximal at pH 4.5 5.0 and at an ionic strength of 1 M. At 37 degrees C, 0.1 M Na acetate buffer, pH 5.0, 1 M NaCl, 10% glycerol, 5% ethylene glycol, 1 mg/ml bovine serum albumin, and 3 mM EDTA, the reaction obeys Michaelis-Menten type kinetics with Km = 17.2 +/- 3.5 microM and kcat = 2.30 +/- 0.33 min-1. The activity assay readily quantitates as little as 0.25 nM of HIV-1 protease. The production of Ang I by the HIV-1 protease is inhibited in the presence of a HIV-1 protease inhibitor. The newly discovered substrate is relatively insensitive to human or monkey serum. Therefore, the effect of sera from 20 patients with advanced acquired immunodeficiency disease syndrome (AIDS) on Ang I production in the above assay system was examined. Results of this study indicate that it may be possible to adapt the above Ang I-based system to determine blood levels of HIV-1 protease inhibitors in AIDS patients during clinical trials. PMID- 1443600 TI - Preparation of DNA topoisomers by RP-18 high-performance liquid chromatography. AB - A method for the separation of superhelical DNA on the basis of superhelical density by reverse-phase HPLC on RP-18 columns is described. The technique can be used to prepare superhelical DNA in milligram amounts and narrow topoisomer distributions in 0.1 mg amounts. We show example separations of the plasmids pUC18 (2687 bp) and pi AN13 (895 bp). While the best separation for pUC18 yields topoisomer distributions of two or three major components, the small plasmid can be separated into single topoisomer fractions. The basis of the separation is probably an interaction of partially opened bases with the hydrophobic column matrix. This hypothesis is supported by the elution behavior of DNA fragments on this column: DNA fragments with sticky ends, even at a length of several hundred base pairs, elute at much higher methanol concentrations than blunt-ended fragments. PMID- 1443601 TI - Characterization of yeast cultivations by steric sedimentation field-flow fractionation. AB - The characterization and quantification of biomass is often time consuming and dependent on the cultivation media and gives no detailed information between cell size and shape and their productivity. By monitoring the bioprocess with steric sedimentation field-flow fractionation (Sd/StFFF) in combination with laser light scattering, not only cell growth, but also the variation of cell size and shape during the cultivation, can be observed. In this work, the feasibility of separating and characterizing cell populations by steric sedimentation field-flow fractionation is demonstrated by its application to three different yeast cultivation broths. For this purpose samples which were collected at different cultivation times were injected into an FFF system. Fractograms were obtained in less than 4 min. Due to the relatively high resolution of the method, a cell sample could be fractionated in several subpopulations differing in their size as well as in their number of buds. PMID- 1443602 TI - Quantitative derivatization and high-performance liquid chromatographic analysis of cyanobacterial heterocyst-type glycolipids. AB - Procedures are described for the rapid and quantitative analysis of cyanobacterial heterocyst-type glycolipids (HGs) by normal-phase HPLC of their per-O-benzoylated derivatives. Total lipids are obtained from 1 ml of nitrogen fixing cyanobacterial culture by triplicate extraction with chloroform/methanol, 1/1 (v/v), and the HGs are isolated from other complex lipids by preparative silica gel TLC. A C18 solid-phase extraction cartridge is used to ensure quantitative salt-free recovery of the HGs, and the purified glycolipids are then rendered uv-absorbing by a per-O-benzoylation derivatization reaction for which optimal conditions have been established. Derivatives are analyzed within 12 min on a 3-microns silica HPLC column using a linear gradient of 2-propanol in n hexane and uv monitoring at 230 nm. The reaction product was also used to determine the relative proportions of the glucosyl and galactosyl epimers of individual members of this class of glycolipid. PMID- 1443603 TI - High-performance liquid chromatography-fluorescence assay of pyruvic acid to determine cysteine conjugate beta-lyase activity: application to S-1,2 dichlorovinyl-L-cysteine and S-2-benzothiazolyl-L-cysteine. AB - An HPLC-fluorescence assay has been developed for the determination of the activity of rat renal cytosolic cysteine conjugate beta-lyase. The method is based on isocratic HPLC separation and fluorescence detection of pyruvic acid, derivatized with o-phenylenediamine (OPD), and is shown to be rapid, specific, and very sensitive. The assay has been evaluated with two model substrates for rat renal cytosolic beta-lyase, notably S-1,2-dichorovinyl-L-cysteine (DCVC) and S-2-benzothiazolyl-L-cysteine (BTC). Equimolar formation of pyruvic acid and 2 mercaptobenzothiazole, a chromophoric thiol, indicated that pyruvic acid formation actually reflects the beta-elimination activity of beta-lyase during the beta-elimination of BTC. From this it follows that the pyruvic acid assay can be applied to the measurement of the beta-elimination activity of this enzyme, independent of the presence of chromophoric groups or radiolabels in substrates. Due to the large linear range and the very high sensitivity of the present HPLC fluorescence assay (detection limit, 7.5 pmol of pyruvic acid), both good and poor substrates of beta-lyase can be measured. Enzyme kinetic data are presented for the model substrates BTC and DCVC and for four structurally related S-2,2 difluoroethyl-L-cysteine conjugates. PMID- 1443604 TI - Sequencing of peptides and proteins from the carboxy terminus. AB - A new chemical method for carboxy-terminal (C-terminal) protein sequencing has been developed. This approach has been successfully used to sequence 5 residues of standard proteins and 5 to 10 residues of synthetic peptides at low nanomole levels. The sequencing procedure consists of converting the C-terminal amino acid into a thiohydantoin (TH) derivative, followed by transformation of the TH into a good leaving group by alkylation. Next, the alkylated TH is cleaved mildly and efficiently with (N = C V S)- anion, which simultaneously forms a TH on the newly truncated protein or peptide. Thus, after the initial TH derivatization, there is no return to a free carboxyl group at the C-terminus. An additional benefit of this method is that the alkylating moiety can be chosen with a variety of properties allowing for variation in the detection method. This chemistry has been adapted to automated protein sequencers with a cycle time of about 1 h. PMID- 1443605 TI - Quantitative determination of hydroxy fatty acids as an indicator of in vivo lipid peroxidation: oxidation products of arachidonic and docosapentaenoic acids in rat liver after exposure to carbon tetrachloride. AB - An improved gas chromatography-mass spectrometry method has been applied to the quantitation of both in vitro and in vivo products of lipid peroxidation in rat liver stimulated with carbon tetrachloride. The method avoids problems of autoxidation of unsaturated fatty acids during sample preparation, and the sensitivity permits assays on as little as 1 mg of tissue. This permits small samples of tissue to be obtained by biopsy from the same organ, thus making it possible to perform in vivo time studies on a single animal. Lipids from whole tissue or cell preparations are simultaneously extracted and reduced by catalytic hydrogenation and then saponified and derivatized to their pentafluorobenzyl esters and trimethylsilyl ethers. Quantitation is accomplished by negative ion chemical ionization gas chromatography-mass spectrometry, using either deuterated compounds or naturally occurring fatty acid metabolites as internal standards. Hydroxy fatty acids which result from reduction of the hydroperoxides of arachidonic and docosapentaenoic acids are found to increase within 20 min after exposure of liver or hepatocyte suspensions to carbon tetrachloride. PMID- 1443606 TI - Immunoaffinity chromatography using electroelution. AB - Immunoaffinity chromatography and electroelution of protein from solid-phase matrices are two powerful tools often used to purify proteins. In this study, we combined these two techniques and found that antigen was effectively recovered from immunoaffinity resins by electroelution. Yields ranged from 90.5% to 62.8%, with a mean of 74.0 +/- 7.4% (mean +/- standard deviation). A major portion of the eluate, 79.4 +/- 13.1%, was concentrated in a volume of 100 microliters and 94.0 +/- 2.0% was recovered in 200 microliters, even when 1 ml of resin was used. Electroelution had no major effect on the electrophoretic mobility of the antigen. Two distinct antigens, a relatively hydrophilic 230-kDa protein and a hydrophobic 28-kDa protein were successfully electroeluted. In addition two types of immunoaffinity resins, monoclonal antibody covalently linked to CNBr-activated Sepharose or immobilized protein A, were found to be compatible with this method. PMID- 1443607 TI - Affinity electrophoretic detection of primary amino groups in nucleic acids: application to modified bases of tRNA and to aminoacylation. AB - Thiolation of primary amino groups in tRNA with the heterobifunctional reagent N succinimidyl 3-(2-pyridyldithio)propionate gives rise to species which are retarded during electrophoresis in organomercury-containing polyacrylamide gels. Since such amino groups occur, as far as is known, only as part of the modified bases 3-(3-amino-3-carboxypropyl)uridine and N-2-(5-amino-5 carboxypentyl)cytidine or as the alpha-amino group of aminoacylated tRNAs, this extension of the principle of affinity electrophoresis can be used for the detection and analysis of a specific functional group in both single tRNA species and in a mixed population. The strength of the interaction may be quantified and provides information on the chemical environment/conformation of the derivatized bases. PMID- 1443609 TI - A novel spectroscopic titration method for determining the dissociation constant and stoichiometry of protein-ligand complex. AB - We offer a new titration protocol for determining the dissociation constant and binding stoichiometry of protein-ligand complex, detectable by spectroscopic methods. This approach neither is limited to the range of protein or ligand concentrations employed during titration experiment nor relies on precise determinations of the titration "endpoint," i.e., the maximal signal changes upon saturation of protein by ligand (or vice versa). In this procedure, a fixed concentration of protein (or ligand) is titrated by increasing volumes of a stock ligand (or protein) solution, and the changes in the spectroscopic signal are recorded after each addition of the titrant. The signal for interaction between protein and ligand first increases, reaches a maximum value, and then starts decreasing due to dilution effect. The volume of the titrant required to achieve the maximum signal changes is utilized to calculate the dissociation constant and the binding stoichiometry of the protein-ligand complex according to the theoretical relationships developed herein. This procedure has been tested for the interaction of avidin with a chromophoric biotin analogue, 2-(4' hydroxyazobenzene)benzoic acid by following the absorption signal of their interaction at 500 nm. The widespread applicability of this procedure to protein ligand complexes detected by other spectroscopic techniques and its advantages over conventional methods are discussed. PMID- 1443608 TI - A quantitative microassay of carbohydrate-mediated cell adhesion to glycoconjugates immobilized on polystyrene plates. AB - A microadhesion assay that allows the quantitative determination of carbohydrate mediated cell adhesion to glycoconjugates immobilized on 96-well polystyrene plates has been developed. After dislodging nonadherent cells by centrifugation, specifically bound cells are quantified by colorimetric analysis of a blue formazan product generated from the dye 3-(4,5-dimethylthiazol-2-yl-2,5 diphenyltetrazolium bromide by enzymatic reduction. Carbohydrate specificity of the cell adhesion was demonstrated by inhibition analyses and the general applicability of the assay was proved with indicator cells of three different origins: mouse fibrosarcoma cells, Chang liver cells, and human breast carcinoma cells (MDA-MB 231). PMID- 1443610 TI - The use of capillary electrophoresis in a micropreparative mode: methods and applications. AB - The ability to collect sufficient quantities of analytes from capillary electrophoresis for subsequent analyses is demonstrated. Fractions collected have been analyzed using the following techniques: capillary electrophoresis, mass spectrometry, and protein sequencing. Fractions can be collected directly into small volumes of buffer or directly onto membrane surfaces. Relevant parameters such as capillary diameter, mass loading, and separation parameters are addressed. PMID- 1443611 TI - A steady-state kinetic method for the verification of the rapid-equilibrium assumption in allosteric enzymes. AB - A method for testing the validity of the rapid-equilibrium assumption as it might apply to allosteric enzymes using exclusively steady-state kinetic data is presented. The method is based upon a recognition that the ratio of apparent dissociation constants for the allosteric ligand, obtained under conditions of limiting and saturating substrate concentration, must yield the thermodynamic value for the coupling parameter between the substrate and allosteric ligand even in the general steady-state case. If this value is found to be equal to the apparent coupling parameter determined from the ratio of limiting values of the Michaelis constant for substrate obtained in the absence and saturating presence of the allosteric ligand, then the substrate can be correctly viewed as effectively achieving a binding equilibrium with the enzyme in the steady-state. The utility and limitations of this method are demonstrated by examining the ADP activation of beef heart mitochondrial NAD-dependent isocitrate dehydrogenase. PMID- 1443612 TI - Selection of COS cell mutants defective in the biosynthesis of heparan sulfate proteoglycan. AB - A simple procedure using human basic fibroblast growth factor (FGF) was utilized for the selection of COS cell mutants with defects in the biosynthesis or expression of heparan sulfate proteoglycan (HSPG). Our approach was based on the strong binding affinity exhibited by COS cells to human basic FGF that had been adsorbed to plastic dishes. Cell binding to basic FGF could be inhibited by heparin and heparan sulfate (HS), but not by chondroitin sulfate, dermatan sulfate, keratan sulfate, or hyaluronic acid, suggesting that the cell binding involved an interaction between basic FGF and cell surface heparin-like molecules. COS cells were treated with ethyl methanesulfonate and four stable mutants were subsequently isolated that did not bind strongly to basic FGF adsorbed to plastic. These mutants cell lines (CM-2, CM-8, CM-9, and CM-15) exhibited significantly reduced 35SO4 incorporation into HS (40-70% depending on the cellular pool analyzed). In one of these cell lines, CM-15, the incorporation of [6-3H]glucosamine into HS was unaltered, suggesting that the extent of oligosaccharide polymerization was equivalent to that observed for the wild-type cells. Structural analysis revealed that N-sulfated glucosamine residues were present much less frequently in HS derived from these cells as compared with that derived from wild-type cells. Furthermore, CM-15 was found to be three-fold deficient in HS N-sulfotransferase activity, but contained wild-type levels of HS O-sulfotransferase activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443613 TI - A method for measuring H2O2 based on the potentiation of peroxidative NADPH oxidation by superoxide dismutase and scopoletin. AB - NADPH oxidation catalyzed by horseradish peroxidase is considerably increased by scopoletin and superoxide dismutase. These effects were used to develop a method for measuring H2O2 in a horseradish peroxidase, superoxide dismutase, and scopoletin system by measuring the NADPH oxidation rate. The optimal concentration of each reactant was determined. H2O2 could be detected and measured when it was present free in the medium or when it was produced by an H2O2-generating system, such as glucose-glucose oxidase or NADPH oxidase from thyroid plasma membranes. H2O2 was measured either by taking aliquots of the incubation medium or by placing NADPH directly in the medium and following the kinetics of NADPH oxidation. This latter approach required smaller amounts of biological material. In contrast to other methods, the H2O2 which is measured is regenerated. This method is 10 times more sensitive than the standard scopoletin method for H2O2 measurement and will detect a H2O2 production rate as low as 0.2 nmol per hour. The method is particularly suitable for biological systems in which small quantities of biological material are available. PMID- 1443614 TI - Effect of formaldehyde on the efficiency of hybridization of DNA immobilized on nitrocellulose filters. AB - We report in this study that under certain conditions formaldehyde interacts with DNA and makes it more efficient for hybridization on nitrocellulose filters. Hybridization signals of formaldehyde-treated DNA are stronger (up to 10 fold) as compared with that of the heat- or alkali-denatured DNA. Various parameters of the DNA-formaldehyde reaction are optimized as follows: (a) 6 x SSC, 10% formaldehyde, 60 degrees C, 20-30 min, reaction volume 10-200 microliters or (b) 6 x SSC, 5% formaldehyde, 98 degrees C, 15 min, reaction volume 10-200 microliters. Treatment of agarose gels after electrophoresis with formaldehyde improved both the transfer of DNA and the efficiency of hybridization. The following conditions are recommended for gel treatment: denaturation in 0.3 N NaOH, 1 M NaCl followed by neutralization with 0.5 M phosphate buffer, pH 7.0, containing 10% formaldehyde at 60 degrees C for 20 min. PMID- 1443615 TI - The mapping by high-pH anion-exchange chromatography with pulsed amperometric detection and capillary electrophoresis of the carbohydrate moieties of human plasma alpha 1-acid glycoprotein. AB - The reducing oligosaccharides released from alpha 1-acid glycoprotein (AGP) by conventional hydrazinolysis have been analyzed by two different mapping techniques, using high-pH anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) and capillary electrophoresis (CE) with uv detection at 190 nm. The CE measurements proved about 4000 times more sensitive than the measurements by HPAE-PAD. The N-glycan pool was fractionated by Mono Q anion exchange chromatography, and individual fractions so obtained were desialylated using Vibrio cholerae neuraminidase. The resulting asialo-N-glycans were further analyzed by HPAE-PAD, revealing 2 major, 4 intermediate, and 4 small peaks and at least 3 spikes, which counted for at least 13 different asialo-N-glycans. The carbohydrate structures were tentatively assigned by comparison of the Mono Q separated N-glycans with the known AGP carbohydrate structures and known structures contained in a mapping database that allows structural assignment of N glycans by mere comparison of retention times. In addition to the hitherto known AGP carbohydrate structures, we have tentatively identified a number of sulfated N-glycans that are currently being analyzed in more detail. We have also compared the glycan pools recovered from AGP using hydrazinolysis and glycopeptidase F (PNGase F). Approximately 40 distinct peaks could be detected in the hydrazinolysis-derived N-glycan pool by either technique (HPAE-PAD and CE), while about 30 distinct peaks were detected in the N-glycan pool derived by PNGase F digestion of the tryptic AGP digest of the same batch of AGP. These differences were attributed to an increased desialylation (approximately 3 mol%) during hydrazinolysis, based on the detection by HPAE-PAD and CE of free sialic acid and monosialylated oligosaccharides in the glycan pool derived by conventional hydrazinolysis. The integrity of the N-glycans' chitobiose core was examined by 500-MHz 1H NMR spectoscopy. The hydrazinolysis procedure could be optimized such that the hydrazinolysis-derived N-glycan pool was chromatographically essentially identical to the PNGase F-derived N-glycan pool. Hydrazinolysis proved best, with practically no loss of N-acetlylneuraminic acid and the closest resemblance to the PNGase F-derived N-glycan pool, using an automated apparatus. Notably, it was recognized that, in our hands, PNGase F digestion in the presence of sodium dodecyl sulfate resulted in partial desialylation of the liberated N-glycans. PMID- 1443616 TI - Dynamically modified, biospecific optical fiber sensor for riboflavin binding protein based on hydrophobically associated 3-octylriboflavin. AB - A new approach to the production of optical fiber sensors is described which is based on a dynamic modification procedure. In this approach, the optical fiber surface is rendered hydrophobic through the covalent attachment of a C18 moiety. Specific sensing ligands are then associated with this surface through either their inherent or designed hydrophobicity. To investigate the feasibility of the approach, an optical fiber sensor has been constructed for riboflavin binding protein in which 3-octylriboflavin is associated with the fiber surface. Fluorescence quenching occurs upon binding of the protein to the immobilized riboflavin derivative. The sensor possesses a minimum measurable quantity of 7.3 pmol of binding protein in a probe volume which is less than 10 microL. With this approach, the sensing surface was repetitively regenerated 15 times over a 1-h period with less than a 5% variation in sensor-to-sensor performance. The approach is general, and with minor variations it can be used in a variety of sensing situations. PMID- 1443617 TI - Analysis of free intracellular nucleotides using high-performance capillary electrophoresis. AB - High-performance capillary electrophoresis (HPCE) with UV absorbance detection (254 nm) has been applied for analyzing intracellular free ribonucleotides. The nucleotide profiles obtained from peripheral blood lymphocytes differ from those obtained from Molt4 human leukemic cells. With a 140 mM borate buffer, pH 9.4, a nearly complete profile can be obtained in 25 min. HPCE has comparable resolution to that of high-performance liquid chromatography (HPLC) but is faster in terms of time per sample run (25 min vs 45 min) and requires much less sample (nanoliter range for HPCE vs microliter range for HPLC). PMID- 1443618 TI - Automated rate nephelometric determination of apolipoproteins AI and B in human serum by consecutive addition of antibodies. AB - A precise, rapid, automated, rate nephelometric immunoassay for apolipoprotein AI (APA) and apolipoprotein B (APB) is described. Both analytes are determined by a "one-pot" procedure which uses consecutive addition of the corresponding antibodies. Poly(oxyethylene) type nonionic surfactants are used to selectively inhibit the APB reaction after the maximum reaction rate has been reached and to enhance the APA immunoreactivity. The assay range for APA is 0.3-3.8 g/L and for APB 0.2-3.0 g/L. The new assay was compared to commercial rate nephelometric methodology. Both methods were shown to be mutually unbiased for APA and APB determinations in human serum. PMID- 1443619 TI - Voltammetric measurement of oxygen in single neurons using platinized carbon ring electrodes. AB - Naflon-coated ultrasmall platinum ring electrodes have been implanted in the giant dopamine neuron of the pond snail Planorbis corneus, and the oxygen concentration inside these single neurons has been estimated. Experimental data suggest that the intracellular oxygen level in the identified dopamine neuron of P. corneus is approximately 0.032 mM. The oxygen concentration immediately outside the cell (ca. 10 microns away from the cell) is 0.041 mM. Furthermore, staircase voltammetry can be used to monitor dynamic changes in oxygen concentration inside the cell after bathing with Ringer's solution saturated with air/oxygen. Data obtained for intracellular oxygen concentrations suggest that intracellular oxygen consumption is increased following potassium chloride induced stimulation of these cells. PMID- 1443620 TI - Background correction by wavelength modulation for pulsed-laser-excited atomic fluorescence spectrometry. AB - Instrumentation was constructed to modulate the dye laser wavelength for background correction in laser-excited atomic fluorescence spectrometry (LEAFS). To achieve wavelength modulation a piezoelectric pusher was used to drive the wavelength tuning mirror in a laboratory-constructed grazing incidence dye laser. The laser pulses were synchronized with the piezoelectric pusher movement so that alternate laser pulses measured the atomic fluorescence signal at the analytical atomic spectral line (on-line) and the background signal at a wavelength displaced to one side of the atomic line (off-line). The background-corrected signal was obtained by subtracting the off-line "background" from the on-line "signal plus background". The spectral line width (fwhm) of the dye laser was 0.003 nm, while the wavelength modulation interval was controllable over the range from 0 to 0.2 nm with a spectral resolution limited only by the spectral line width of the laser. This type of background correction could, in principle, be applied to other types of tunable lasers such as pulsed Ti: sapphire lasers. The performance of background correction by wavelength modulation (WM) was demonstrated by measurement of sodium resonance fluorescence in an air-acetylene flame and by thallium nonresonance fluorescence in a graphite furnace. The experimental data indicated that the wavelength modulation corrected, effectively and quantitatively, for flame background, blackbody emission from a graphite furnace, and scatter of laser radiation off aluminum chloride (1 mg/mL as AI) matrix particles in both the furnace and the flame. Analytical results were in good agreement with certified values for the determination of sodium in standard reference materials by the use of modulated LEAFS. PMID- 1443621 TI - Bioanalytical applications of partitioning in aqueous polymer two-phase systems. PMID- 1443622 TI - Time-of-flight mass spectrometry for the structural analysis of biological molecules. PMID- 1443623 TI - Use of capillary zone electrophoresis to evaluate the binding of anionic carbohydrates to synthetic peptides derived from human serum amyloid P component. AB - Capillary zone electrophoresis was used to study interactions between anionic carbohydrates and synthetic peptides derived from the heparin-binding region of human serum amyloid P component. The method involves quantitation of unbound peptides after a charge-dependent electrophoretic separation of the peptide carbohydrate mixture. The concentrations of free peptide were determined by extrapolating the obtained peak areas of the peptide in the presence of ligand to a standard curve. Dissociation constants in the 10(-5) M range were determined, and differences in binding affinity of various peptide modifications were illustrated. The assay requires minute amounts of material (sample volume is 7-15 nL), and as long as the reactants are soluble at the chosen conditions, no modifications or special characteristics of the interacting molecules are needed for their identification. It should be possible to use electrophoretic separation in capillaries to evaluate the binding of peptides to any ligand as long as the differences in charge/mass ratio between free and complexed peptide are of a sufficient magnitude as in the peptide-heparin binding demonstrated here. PMID- 1443624 TI - Detection of antistreptolysin O antibody: application of an initial rate method of latex piezoelectric immunoassay. AB - Latex plezoelectric immunoassay (LPEIA) is a new latex immunoassay using a plezoelectric quartz crystal (Kurosawa et al. Chem. Pharm. Bull. 1990, 38, 1117). This assay requires no immobilization of antigen or antibody on an electrode surface of a plezoelectric crystal, while the immobilization is indispensable for ordinary immunoassays using a plezoelectric crystal as a microbalance. The present paper improves a previous method (end-point analysis) by introducing the initial rate method using a batch cell; reduction of assay volume (1.2 mL) and shortening of assay time (2-3 min) were achieved. This assay was applied to the detection of antistreptolysin O antibody (ASO) in serum. The frequency change was proportional to the ASO concentration up to 1040 IU mL-1, and the method has good sensitivity for actual clinical application. The volume of serum required for the assay was 0.02 mL. Twenty-four clinical specimens were analyzed with this LPEIA, and the values obtained were compared with those obtained with a turbidimetric latex agglutination method. The correlation coefficient between these values was 0.950 (P < 0.01). PMID- 1443625 TI - Quantitative determination of glucose in blood plasma and in fruit juices by combined WATR-CPMG 1H NMR spectroscopy. AB - The quantitative analysis of pure glucose solution < or = 225 mM (< or = 40.8 mg/mL) in 90/10 H2O/D2O was successfully completed in dilute aqueous solution by the WATR-CPMG method whereby the T2 of the water resonance is manipulated by the WATR method followed by elimination of the water peak by the CPMG pulse sequence. The method was applied to the quantitative analysis of total glucose in blood plasma from human subjects undergoing the oral glucose tolerance test in the teaching hospital, and the results were compared to those obtained using a standard glucose oxidase method in a hospital chemical pathology laboratory. The accuracy of the results obtained using the WATR-CPMG method were generally within 5% of the glucose oxidase method. The coefficient of variation was determined to be better than 4% using plasma samples of diabetic subjects. Application to the quantitative analysis of orange and guava juice was also successfully demonstrated. PMID- 1443626 TI - On-line coupling of in vivo microdialysis with tandem mass spectrometry. AB - The capability of interfacing in vivo microdialysis with mass spectrometry has been demonstrated. The goal of this research was to demonstrate the feasibility of real-time analysis in biological systems using microdialysis in combination with tandem mass spectrometry (MS/MS). Microdialysis sampling was accomplished by surgically implanting a small microdialysis probe into a tissue or area of interest. Molecules diffuse through the membrane of the microdialysis probe due to concentration differences. These molecules are collected in a sample loop and analyzed by tandem mass spectrometry. Sequential injections can be made in as little as 2 min. This capability is advantageous in the study of molecules with very rapid elimination rates. Tris(2-chloroethyl)phosphate (TRCP) was used as a model compound in the development of this analytical technique. As an example of an application of the microdialysis/MS/MS technique, plasma concentration vs time curves were obtained and compared with the plasma concentration profiles obtained using conventional studies. For the microdialysis/MS/MS studies, the average slope from three animals was -0.086 min-1. In comparison, the average slope from four animals from the conventional studies was -0.035 min-1. PMID- 1443627 TI - Penicillin sensor based on a microarray electrode coated with pH-responsive polypyrrole. PMID- 1443628 TI - Purification of beta-cyclodextrin. PMID- 1443629 TI - The fountain cell: a tool for flow-based spectroscopies. PMID- 1443630 TI - Human in vivo percutaneous absorptiometry using the laser-photoacoustic method. PMID- 1443631 TI - Spectrophotometric enzyme-amplified immunoassay for thyroid stimulating hormone. AB - Thyroid stimulating hormone (TSH) regulates the function of the thyroid gland. Its determination at low concentrations in serum is useful in the diagnosis of hyperthyroidism. In this paper, it is detected using a spectrophotometric enzyme amplified immunoassay. The reporter enzyme is alkaline phosphatase and its substrate is flavin adenine dinucleotide phosphate (FADP). Reaction with alkaline phosphatase converts FADP into flavin adenine dinucleotide (FAD), which, unlike FADP, re-activates apo-D-amino acid oxidase (apo-AOD). Re-activation of apo-AOD allows the product of the reporter enzyme to be amplified. The lower limit of detection for TSH by this method is 0.06 microU cm-3. This compares with 0.54 microU cm-3 for an identical assay in which p-nitrophenyl phosphate was the substrate for alkaline phosphatase. Contaminating alkaline phosphatase was removed from the reagents by affinity chromatography. PMID- 1443632 TI - Determination of ultrafiltrable zinc in human milk by electrothermal atomic absorption spectrometry. AB - Percentages of non-protein-bound zinc in human milk have been reported by different workers, but ultrafiltration and zinc determination in human milk have not been comprehensively examined. However, zinc contamination and zinc membrane binding have been described for the determination of non-protein-bound zinc in serum. In this work, ultrafiltration was studied in terms of zinc contamination and zinc membrane binding. An MPS-1 micropartition system fitted with a YMT membrane was used. Zinc contamination was found to be less than 276 nmol dm-3 and the zinc recovery was 85 +/- 4%. The conditions for electrothermal atomic absorption spectrometry were also studied. The detection limit was found to be 26.4 nmol dm-3 and the upper linear range was 4 mumol dm-3. The precision varied from 3% (within-run) to 17% (between-run). The recovery of standard additions was 95 +/- 7% (n = 30, different human milk ultrafiltrate samples). Physiological values varied from 0.46 to 84 mumol dm-3 (4-56% of zinc in whole human milk). Expressed in mumol dm-3, zinc in human milk ultrafiltrate decreased slightly through the lactation period, whereas expressed as a percentage of the total zinc in milk, zinc in human milk ultrafiltrate remained constant from day 2 to day 69 post partum. PMID- 1443633 TI - Determination of ascorbic acid in pharmaceuticals and urine by reverse flow injection. AB - Two reverse flow injection (FI) methods, using spectrophotometric detection, are proposed for the determination of ascorbic acid. Both methods are based on its reaction with the ethylenediaminetetraacetic acid-CoIII complex in a medium of 5% diethylamine. In the first method, using the peak-height FI technique, ascorbic acid is determined over the range from 2 x 10(-4) to 5 x 10(-3) mol dm-3 and in the second, using the peak-width FI method, the working range is extended (2 x 10(-3)-5 x 10(-2) mol dm-3). Both FI methods were applied to the determination of ascorbic acid in pharmaceuticals while the peak-height FI technique was also used to determine ascorbic acid in urine. PMID- 1443634 TI - Scanning probe microscopies for high-resolution characterization of electrochemical sensors. Plenary lecture. AB - A better understanding of tailored electrodes and electrochemical sensors requires a more detailed picture of their surfaces. New scanning probe techniques, such as scanning tunnelling or scanning bioelectrochemical microscopies, offer unique opportunities for high-resolution in situ characterization of tailored electrodebased sensors. Scanning tunnelling microscopy provides valuable information on the topography of pre-treated surfaces, the heterogeneity of composite electrodes, the morphology of electropolymerized films, the packing arrangement of adsorbed monolayers and the microdistribution of immobilized biological components. Scanning bioelectrochemical microscopy is shown to be extremely useful for the mapping of localized biological activity and the monitoring of dynamic biological events. Valuable insights are achieved by correlating the structural features with the preparation/modification conditions and the subsequent sensing performance. Such correlations can facilitate the predictive design of increasingly better sensors. PMID- 1443636 TI - Spectrofluorimetric determination of tetracycline and anhydrotetracycline in serum and urine. AB - A spectrofluorimetric method, involving alkaline degradation and formation of a magnesium complex, is described for the determination of tetracycline (TC) and anhydrotetracycline (ATC) in their mixed solution. Tetracycline is degraded and determined in alkaline solution. This treatment of ATC produces almost no fluorescence, but a fluorescent magnesium complex forms at pH 7.5. Several synthetic samples of TC and ATC, with TC:ATC ratios ranging from 50:1 to 1:50, were analysed. The recoveries of TC and ATC are about 71-76 and 61-63% in serum, respectively, and are all about 100% in urine. PMID- 1443635 TI - Determination of lithium at ultratrace levels in biological fluids by flame atomic emission spectrometry. Use of first-derivative spectrometry. AB - The use of zero-order and first-derivative flame emission spectrometry has been investigated for the determination of basal concentrations of lithium in serum and urine at the microgram dm-3 level. No significant matrix effect was observed; however, it was necessary to make use of background correction techniques. Two or three wavelength measurements and first-derivative spectrometry were used for this purpose; both methods gave similar results. Detection limits for serum of approximately 0.09 micrograms dm-3 were found by both zero-order and first derivative emission measurements, while normal lithium levels were found to be 29.3 and 1.17 micrograms dm-3 for urine and serum, respectively. PMID- 1443638 TI - Pyrolysis-gas chromatography-mass spectrometry of a series of bile acid sequestrants. AB - Pyrolysis of a series of polymers based on polystyrene and used as bile acid sequestrants produced characteristic mixtures of compounds which were analysed by gas chromatography-mass spectrometry. The nature of the substituent groups was clearly apparent while the polymer backbone gave rise to representative styrenes. The reproducibility of the results was examined by experimenting with the temperature of pyrolysis. It was found that at low temperatures very little fragmentation of the polystyrene backbone occurred but the substituents were still released in high yield. The orientation of the various substituted styrenes generated by pyrolysis was confirmed by the use of gas chromatography with infrared and mass spectrometric detection. PMID- 1443637 TI - Microbiological assay of avoparcin in animal feeds and pre-mixes--co-operative study. AB - A microbiological method for the determination of the antibiotic growth promoter avoparcin in animal feeds and pre-mixes was first published in 1979. The existing method has been applied to new matrices as commercial use of avoparcin has spread. Problems with the existing analytical procedure have been reported, particularly in Germany. This paper identifies the causes of the problems and includes revisions to the existing analytical procedure. The testing of these revisions in co-operative studies with up to five German official laboratories is also reported. PMID- 1443639 TI - Determination of 4,4'-methylenebis(2-chloroaniline) in urine using capillary gas chromatography and negative ion chemical ionization mass spectrometry. AB - A highly sensitive and specific gas chromatographic-mass spectrometric (GC-MS) assay for the determination of 4,4'-methylenebis(2-chloroaniline) (MBOCA) in urine is reported. It is based on the solvent extraction of the hydrolysed MBOCA conjugates, together with deuterium-labelled benzidine-d8 added as an internal standard, and a two-phase derivatization procedure involving use of pentafluoropropionic anhydride in the presence of ammonia as the phase-transfer catalyst. The reaction is complete within 2 min at room temperature. The pentafluoropropyl derivatives are determined by use of capillary column GC-MS with selected-ion monitoring in the negative ion chemical ionization mode. The lower limit of detection for MBOCA was 1 microgram dm-3 and the calibration graph showed linearity between 10 and 250 micrograms dm-3. The recovery of the analyte added to pooled urine was above 86%. Thirty urine specimens from workers employed in a polyurethane-producing plant were analysed for MBOCA by this method. PMID- 1443640 TI - Micellar electrokinetic capillary chromatography of amoxycillin and related molecules. AB - A micellar electrokinetic capillary chromatographic method has been developed for the qualitative assay of amoxycillin and its degradation products and clavulanic acid. Together with amoxycillin the latter acid is an important constituent in the antibiotic Augmentin. The analytical procedure is fast and analytes can be identified both from their migration times and from changes in migration time observed either at different pH values or in electropherograms run in H2O and D2O based buffers of the same acidity. PMID- 1443641 TI - Simultaneous determination of some antibacterial drugs in isosensitest broth using high-performance liquid chromatography with solid-phase extraction. AB - A method is described for the simultaneous determination of combinations of some antibacterial drugs in a matrix of isosensitest broth. A double solid-phase extraction procedure is described in which trimethoprim and dibromopropamidine isethionate together with 4-chlorophenylbiguanide as internal standard are freed from endogenous components by a cation-exchange extraction cartridge and subsequently removed and individually separated by reversed-phase ion-pair chromatography. Sulfadiazine, sulfamerazine and p-aminobenzoic acid, unretained by ion exchange, are similarly isolated for chromatography by adsorption on a CH bonded phase cartridge and individually assayed using the same chromatographic system. The rationale of the pre-treatment and chromatography is described and the quantitative aspects of the analyses of selected combinations of these drugs are reported. PMID- 1443642 TI - Report of two co-operative trials of a gel permeation chromatographic method for the isolation of pesticide residues from oils and fats. Committee for Analytical Methods for Residues of Pesticides in Foodstuffs of the Ministry of Agriculture, Fisheries and Food. AB - A gel permeation chromatographic (GPC) method for the determination of pesticide residues in fats and oils was subjected to two co-operative trials. Results for organochlorine pesticides (beta-HCH, gamma-HCH, dieldrin, p,p'-DDE and heptachlor) were compared with those obtained using an alumina column clean-up method. No significant differences in the mean values were found between the two techniques using the t-test (5% significance level). Horrat values demonstrated acceptable inter- and intralaboratory precisions for both clean-up techniques. Two organophosphorus pesticides (diazinon and propetamphos) and the synthetic pyrethroid deltamethrin were also determined using the GPC method. However, these compounds were not recoverable using the alumina column method, so no comparisons between the two methods were possible. PMID- 1443643 TI - Flow injection spectrophotometric determination of the antibiotic ciprofloxacin in drug formulations. AB - A flow injection spectrophotometric method for the assay of ciprofloxacin was developed. The method was based on the chelation of iron(III) with the drug in 0.023 mol dm-3 sulfuric acid solution in a 72 cm long coil and the brown-red complex produced was monitored at 447 nm. The super modified simplex computer program was employed for the optimization of the system and chemical parameters with respect to throughput and sensitivity as a measure of system performance. A working range for ciprofloxacin determination of 50-500 ppm for a 110 mm3 sample size with an optimum of 250 samples per hour was achieved with a relative standard deviation of less than 0.92%. The method was successfully applied to the determination of ciprofloxacin in drug formulations. PMID- 1443644 TI - [Bernd Vollmerhaus on his 65th birthday]. PMID- 1443645 TI - [The estimation of the age of the female ibex (Capra ibex ibex L.) by skeletal development]. AB - In female ibex up to an age of six years, a sufficiently accurate age determination can be made based on the degree of skeletal ossification and length of the bones (s. Table 2). Definitive ossification of the epiphyseal discs with the body of the vertebrae in the female ibex is not complete at end of the growth period. Observations with regard to sex-related dimorphism of the skeleton will not be possible until corresponding investigations have been carried out on the buck. PMID- 1443646 TI - [The biological valence of the motion in the radioulnar joints of the cat and dog]. AB - Whereas Kolwe described and measured pronation and supination in the cat as early as 1920, the present study deals with rotation of the lower limb of the cat and dog from both comparative and functional aspects. Active supination predominates in cats during climbing and the capture of prey; in the canine passive supination and rotation of the lower limb are used in conjunction with directional changes involved in the chase. The difference in the extent of inward rotation between long- and short-legged breeds of dogs underscores this hypothesis. PMID- 1443647 TI - [Differentiation of the ruminal epithelium of cattle during intrauterine development]. AB - The prenatal development of the bovine ruminal epithelium was studied with light- and electronmicroscopical techniques. During the period of the nonstratified epithelium a pseudostratified epithelium is found in the dorso-cranial part, whereas the other areas possess a one-layered epithelium, which is, like the pseudostratified epithelium, transformed to a multilayered epithelium from the 7th week onwards. From the 9th week the period of the stratified epithelium starts with the formation of the stratum profundum and stratum superficiale. First signs of keratinization are seen in the superficial cells from 2.3 months onwards. With 4 months fetal cornified cells can be identified, with 5.5 months a single-layered stratum basale is seen on the differentiating papillar connective tissue, and the superficial cells are transformed to balloon-cells. In suprapapillar areas, a stratum spinosum is formed at the prenatal age of 7.5 months. During epitheliogenesis a horizontal and vertical differentiation of the cells can be observed. The first one includes the differentiation of undifferentiated, embryonal cells to the basal cells of the stratum profundum, the latter the development of the basal cells to spinous cells and then to fetal cornified and balloon-cells. The ultrastructural changes during the process of keratinization were especially considered. PMID- 1443648 TI - [Development and cell differentiation of the motor nucleus of the facial nerve of cattle]. AB - The early development, cell-migration and cell-differentiation of the nucleus motorius nervi facialis were studied in 32 bovine embryos with a CRL of 1 to 53 cm by light microscopical techniques. The ventro-medial cell column, a transitory embryonic formation, can be regarded as the origin of the nucleus. From there migrating cells can be demonstrated up to a CRL of 2.7 cm. With 3.8 cm CRL the cells are confined to their definitive location. From 5 cm CRL onwards a subdivision into 4 subnuclei can be seen. By succeeding maturation processes the nucleus of fetuses with 53 CRL acquires the topographical and cellular appearance of mature animals. With the electron microscope the cell-differentiation of the early stages (2.5 and 3.6 cm CRL) was demonstrated. Additionally the ventro medial cell column was studied. The vertical columnar organisation of the neurons of the nucleus facialis shows besides longitudinal orientated guiding structures the migration process which is taken place at a CRL of 2.5 cm. Synaptogenic cell contact are seen from 3.6 cm SSL. At this stage the migration of cells has come to an end. PMID- 1443649 TI - [Typical presentation of the common tendon sheath of the M. flexor hallucis longus and the M. tibialis caudalis in the horse]. AB - The possibilities for imaging soft tissue structures, especially fluid-filled cavities such as articulations, bursae or tendon sheaths, have been improved markedly by sonography in recent years. Ultrasonic examinations were performed on the common tendon sheath of the musculus flexor hallucis longus and the musculus tibialis caudalis, from the medioplantar aspect of the tarsus, in 12 sound adult draft- and warm blood horses, and in 5 animals with a distended common sheath. The diagnostic precision of the sonographic examination of the tendon sheath is excellent and is superior to conventional radiography. A nuclear magnetic resonance tomogram of an isolated equine tarsus is presented for comparison method. PMID- 1443650 TI - [The heterogenicity of the vascular endothelium]. AB - The vascular endothelium has long been considered to be a homogeneous cell type. It is only recently that its remarkable heterogeneity has been shown. The selective and organ-specific adhesion of cells of the immune system, of metastasizing tumor cells and of microorganisms underscores the central position of the endothelium between the circulation and each organ. The use of antibodies and lectins led to the recognition of species-, organ-, and age-specific endothelial cell surface receptors. Identification of the endothelial adhesion molecules and -mechanisms, which are part of the "endothelial organ- and tissue address" would lead to the possibility of blocking the adhesion of cells, such as e.g. tumor cells. PMID- 1443651 TI - [Detection of lectin binding sites in the trophoblast of cattle during early pregnancy]. AB - In the present study we report on the histotopographical distribution of lectin binding sites in the trophoblasts of day 18 to day 40 bovine embryos, using the FITC-labeled lectins BPA, Con A, DBA, GS I, GS II, MPA, PNA, SBA, UEA I and WGA. Lectin binding sites localized in giant binucleate cells differ from those localized in uninucleate cells, indicating changes in the biochemical structure of cell surfaces taking place during differentiation. In the trophoblast of the day 40 embryo, a distinct staining of uninucleate cells was seen after incubation with GS I, Con A and MPA, demonstrating N-acetylgalactosamine (GS I), Mannose (Con A) and Galactose (MPA) moieties, whereas giant binucleate cells showed intense reactions after incubation with DBA and WGA, indicating presence of N acetylgalactosamine (DBA) and N-acetylglucosamine (WGA). GS II (specific for N acetylglucosamine), SBA (specific for N-acetylgalactosamine) and UEA I (specific for L-Fucose) showed no affinity toward any of the examined tissues. We assume, that carbohydrate moieties in trophoblast cells play an important role in fetomaternal cell-cell adhesion and cell migration during implantation and placentation period. PMID- 1443652 TI - [Lysosomal structures in the intestinal epithelium of mammals during their pre- and postnatal development. A micromorphometric-functional synopsis]. AB - The first lysosomes appear in the stratified embryonic intestinal epithelium during its transition into the simple columnar form. This occurs concurrently with the initial villogenesis. Lysosomes situated basally in the epithelium are presumably the precursor of the first giant lysosomes in the lower small intestine of rodents. Immediately after establishment of the simple configuration a special form of secondary lysosomes can be observed, i.e. glycogenosomes, in the ephemerally existing huge glycogen containing areas. During subsequent fetal intestinal development one observes two events in the epithelial cells, which are the same in principle but differ in one essential point, while they exhibit partially impressive structures. On the one hand there are autophagic degenerative lysosomal processes in the villous epithelium until birth, that lead to a surface without villi in the large intestine, where they occur particularly frequently. On the other hand giant lysosomes originate perinatally in the lower small intestine as well as in the caecum and colon ascendens, in which protein molecules, which were transported by a system of inframicrovillar membranes, are lysosomally degraded, which can be defined as a heterophagic event. PMID- 1443655 TI - Structural relationships between the endothelial actin system and the underlying elastic layer in the distal interlobular artery of the rat kidney. AB - The structure of the intracellular actin filaments and the extracellular matrices was studied in the distal interlobular arteries in the rat kidney, employing three different morphological techniques, including rhodamine-phalloidin staining of cryosections, resorcin-fuchsin staining of paraffin sections, and a cold dehydration procedure for electron microscopy. The endothelial cells possess longitudinally running stress fibers. The inner elastic layer is composed of meshworks of elastic fibers encompassing numerous pores. The smooth muscle cells containing abundant actin filaments are arranged circumferentially around the vascular axis. The endothelial stress fibers are found mainly in the basal half of the endothelial cells, and anchor onto the basal cell membranes. The elastic meshworks send off longitudinal branch fibers to contact the endothelial cell membranes at the anchoring sites of stress fibers. In addition circumferential branches run toward the smooth muscle cells. The functional significance of the intracellular contractile apparatus and the extracellular tensile component in small arteries was discussed. PMID- 1443653 TI - Immunohistochemistry of cholinergic receptors. AB - Acetylcholine and its receptors are involved in a variety of important signal transduction processes. As shown here paradigmatically for the human neuromuscular junction and the cerebral cortex, acetylcholine receptors can be visualized immunohistochemically at the cellular and subcellular level under physiological and pathological conditions. At normal motor endplates nicotinic cholinoceptors are localized at the surface of the postsynaptic junctional folds. In myasthenic syndromes investigation of muscle biopsies enables the diagnosis of receptor deficiencies at the ultrastructural level. In normal cerebral cortex pyramidal neurons are equipped with both nicotinic and muscarinic acetylcholine receptors localized to postsynaptic densities. In neuropsychiatric diseases cholinoceptor expression can be monitored at the cellular level by quantitative assessment of immunolabeled cortical neurons. PMID- 1443654 TI - An atlas of glycine- and GABA-like immunoreactivity and colocalization in the cochlear nuclear complex of the guinea pig. AB - The distribution and colocalization of gamma-aminobutyric acid (GABA)- and glycine-like immunoreactivity in the cochlear nuclear complex of the guinea pig have been studied to produce a light microscopic atlas. The method used was based on post-embedding immunocytochemistry in pairs of 0.5-micron-thick plastic sections treated with polyclonal antibodies against conjugated GABA and glycine respectively. Immunoreactive cells, presumably short axon neurones, predominated in the dorsal cochlear nucleus, with mostly single-GABA-labelled cells in the superficial layer, double-labelled in the middle, and single-glycine-labelled in the deep layers. A few large single-glycine-labelled cells, interpreted as commissural neurons, occurred in the ventral nucleus. Scattered double-labelled cells, probably Golgi cells, were seen in the granule cell domain. Immunolabeled puncta of all three staining categories occurred in large numbers throughout the complex, apposed to somata and in the neuropil, showing a differential distribution onto different types of neuron. Three immunolabeled tracts were noted: the tuberculoventral tract, the commissural acoustic stria, and the trapezoidal descending fibres. Most of the fibres in these tracts were single labelled for glycine, although in the last mentioned tract single-GABA- and double-labelled fibres were also found. Some of the immunolabeled cell types described here are proposed as the origins of the similarly labelled puncta and fibres on the basis of known intrinsic connections. PMID- 1443656 TI - Postnatal development of zinc-containing cells and neuropil in the visual cortex of the mouse. AB - The postnatal development of zinc-containing synaptic boutons and their cells of origin in the visual cortex of a pigmented mouse is described. Two phases can be distinguished. During the early phase zinc-containing neuropil is first apparent by postnatal day 3. By day 7 a light, but distinct neuropil staining sketches the primary and secondary visual cortices. The primary visual area contains light precipitate in layers V and VI as well as the monocular portion of layer II/III. The secondary visual areas contain slightly denser precipitate in layers II/III through VI. The transition to the second phase is marked by a large increase in precipitate density by day 11. Thereafter, the intensity of the neuropil staining increases to day 28, first in layer II/III and then in layer V, as the adult pattern of neuropil staining gradually develops. In the primary visual cortex precipitate is dense in layers II/III and V, moderate in layer VI, and sparse in layers I and IV. In the secondary visual areas the precipitate is dense in layers II/III and V and moderate in the lower portion of layer I and in layers IV and VI. Cells of origin of zinc-containing boutons are visible by the end of the second postnatal week in layer II/III of the secondary visual cortex. By 21 days of age the pattern of staining in the mature mouse is established, and cells in layers II/III and VI are labeled in both the primary and secondary visual cortices. The developmental sequence of zinc-containing cells and neuropil does not preclude an involvement of zinc in the postnatal regulation of NMDA receptor function. PMID- 1443657 TI - Enhancement of muscle regeneration in the rat gastrocnemius muscle by low energy laser irradiation. AB - The effect of low-energy laser (He-Ne) irradiation on the rate of skeletal muscle regeneration after partial excision of the rat gastrocnemius muscle was studied using quantitative histological morphometric methods. The injured zones of the experimental rats were subjected to direct He-Ne laser (632.8 nm wavelength) irradiation (6.0 mW for 2.3 min) immediately following injury and once daily thereafter for 5 days. Muscles that were injured as above and subjected to red or room light irradiation served as a control group. The volume fraction (percent of total volume of injured zone) of the mononucleated cells in the injured zone decreased gradually with time after injury, but more rapidly in the laser irradiated muscles than in the control. At 3 days post-injury the myotubes in the laser-irradiated muscles populated a significantly higher percentage (13.9 +/- 1.1%) of the injured area than in the control muscles (7.8 +/- 1.0%). The volume fraction of the young myofibers in the laser irradiated muscles exceeded 30.6 +/- 2.2% and 49.6 +/- 5.6% at 8 and 11 days post-injury, respectively, while in control muscles these structures comprised only 9.6 +/- 1.0% and 27.2 +/- 3.8% of the injured zone at 8 and 11 days after injury, respectively. It is concluded that He-Ne laser irradiation during the regeneration process promotes muscle maturation in the injured zone following partial excision of the rat gastrocnemius muscle. PMID- 1443658 TI - Local signalling in dermomyotomal cell type specification. AB - The development and differentiation of the avian myotome was studied after removal of the neural tube, including neural crest, and after replacement of dorsal half-somites by ventral half-somites. Results show that in the absence of neural tissue myoblast differentiation within the somites does not take place. Ventral half-somites are able to undergo muscle differentiation if they were grafted in place of dorsal half somites. It is suggested that local signals must be responsible for the dorsalisation of the newly formed somite including myoblast differentiation. Neural crest cells are discussed as possible sources of these signals. PMID- 1443659 TI - Expression of alpha-tropomyosin during cardiac development in the chick embryo. AB - A new monoclonal antibody (mAb) that recognizes alpha-tropomyosin in cardiac muscle cells was used in a qualitative (polyacrylamide gel electrophoresis and indirect immunofluorescence) and quantitative (fluorescence-activated cell sorting) study of the expression of this protein during heart development. alpha Tropomyosin expression was weak in early stages of chick embryo development (Hamburger and Hamilton stage 18), and increased steadily until Hamburger Hamilton stage 40. In early stages, the protein was found mainly in cytoplasm, whereas by the final stages, it was more abundant in the cytoskeletal compartment. The mAb cross-reacted with alpha-tropomyosin in smooth and striated muscle cells from chickens, mice, and humans, but did not cross-react with nonmuscle tropomyosin. PMID- 1443660 TI - Effects of prostaglandin inhibition on the bone activities associated with the spontaneous drift of molar teeth in the rat. AB - Little is known about local bone regulation that enables spontaneous molar tooth drift. In this study the role of prostaglandins (PGs) were investigated in the rat by inhibiting PG-synthesis with indomethacin (7 mg/kg/d). Untreated animals were killed at the start of the experiment, while treated ones were killed after 3, 7, or 14 days of treatment. Mandibles were processed for histomorphometry without demineralization. Changes in osteoclasts and extent of the different steps of the bone remodeling sequence (resorption, reversal, and formation) were assessed along the remodeling side of the socket of the buccal root of the first molar. The total number of osteoclasts decreased after 7 days of PG inhibition (P < 0.01 vs controls) and then partially recovered. This change was due to a sharp decrease in active cells on day 7 (P < 0.01), while inactive cells remained unchanged throughout the experimental period. The extent of resorption fell on day 7 (P < 0.01) and then recovered almost to the control level on day 14. Reversal at first increased insignificantly and thereafter decreased (P < 0.02) for the remaining 7 days. Formation was modified only on day 14; at that time it had doubled compared with controls. These results show that PGs are involved in the local regulation of bone remodeling accompanying tooth drift. Resorption inhibition was partial, indicating that other factors participate with PGs in this regulation; in addition, the trend to recovery observed at the end of the experimental period suggests that these factors can take over from PGs to achieve the necessary remodeling of the socket. PMID- 1443661 TI - Adaptation of cancellous bone to aging and immobilization in growing rats. AB - Two-and-half-month-old female rats were subjected to right hindlimb immobilization or served as controls for 0, 1, 2, 8, 14, and 20 weeks. The right hindlimb was immobilized by bandaging it against the abdomen, thus unloading it. Cancellous bone histomorphometry was performed on microradiographs and double fluorescent labeled 20 microns sections of the distal femoral metaphyses. Primary spongiosa bone loss occurred rapidly by 2 weeks, and secondary spongiosa bone loss occurred rapidly by 8 weeks of immobilization, and then equilibrated at 60% less bone mass than age-related controls. The negative bone balance induced by immobilization was caused by transient increase in bone resorption, decrease in bone formation, and longitudinal bone growth. The dynamic data of secondary spongiosa cancellous bone showed that percent eroded perimeter was transiently elevated by 55 to 82% between 1 and 8 weeks, percent labeled perimeter was transiently depressed by 32% to 50% between 1 and 14 weeks, mineral apposition rate was depressed by 23% and 19% at 1 and 2 weeks, and bone formation rate-bone area referent was transiently depressed by 35% and 59% at 1 and 2 weeks. All the above parameters were at age-related control levels by 20 weeks of immobilization. However, bone formation rate-tissue area referent was depressed ( 65%) throughout the study. Immobilization depressed completely longitudinal bone growth by 2 weeks and remained so. Only 0.65 mm of new metaphysis was generated in the immobilized versus 2.1 mm in controls during the study period. The immobilization induced an early cancellous bone loss which equilibrated at a new steady state with less bone and a normal (age-related control) bone turnover rate. When these findings were compared to an earlier study of 9-month-old virgin females subjected to right hindlimb immobilization up to 26 weeks, we found the adaptive responses of the cancellous bone were identical except that they occurred earlier and equilibrated sooner in younger rats. PMID- 1443662 TI - Elastic fibers in the duct system of the rat submandibular salivary gland. AB - The submandibular salivary gland originates from the floor of the mouth whose mucosa contains elastic fibers. Therefore, such fibers were sought in the duct system of the derivative organ. In adult rats, light microscopy has indeed revealed fine, circumferential, elastic fibers near the basement membrane of the duct epithelium. In the larger extralobular ducts, they were separated from several layers of longitudinal elastic fibers by a capillary-rich zone sparse in elastic fibers except for fine angular ones. More peripherally, larger angular appearing fibers were frequently present near the submandibular parasympathetic ganglia in the duct wall. As duct diameter decreased, elastic fiber size and number diminished. Intralobularly, the smaller striated ducts, granular and intercalated ducts, and acini generally lacked such fibers. Electron microscopy of the extraglandular portion of the main duct revealed fibrils extending from both fibroblasts and elastic fibers that were close to the epithelium. Microfibrils coursed from them toward the lamina densa. Anchoring filaments joined the lamina densa to the basal plasma membrane of the epithelium. Elastic fibers also appeared to connect to both capillaries and collagen via finer intermediate structures. These associations might permit dynamic interactions of fibroblasts, fibers, smaller fibrillar components, vasa, and the duct epithelium. This interplay could occur during feeding and grooming when tongue protrusion and neck extension stretch the submandibular duct and the gland itself. As a result, the tensile forces engendered could modify cell geometry and the calibers of the larger ducts' lumens and intercellular spaces, thus affecting the flow and composition of salivary secretion. PMID- 1443663 TI - Morphology of the kidney of the platypus (Ornithorhynchus anatinus: Monotremata). AB - The platypus kidney shows morphological similarities to those of other mammals. Macroscopically, the cortex is easily distinguishable from the fairly wide medulla. Within the medulla, no clear border is observed between the inner and outer zones. Light and transmission electron microscopically, the glomeruli show quite similar architecture to those of other mammals; however, the glomerular lobulation is very clear. The glomerular tufts are rather simple, but capillary lumen varies widely in size, which is one of the unique features of the platypus kidney. The urinary tubule is generally similar to that of human and other mammals in shape and segmentation; however, the staining specificities of histochemical reactions and the shape of epithelial cells of the Henle's loop differ from those of other mammals. The most conspicuous features are: 1) although no protein casts are found in the tubular lumina, epithelial cells of the proximal convoluted tubule (PCT) have numerous electron-dense vesicles as in human nephrotic kidneys; and 2) the platypus Henle's loop consists of the thick epithelial cells similar to the mammalian type nephron of birds. As compared to those of other mammals such as humans and rats, our observations suggest that the platypus kidney is less developed, in terms of evolution. PMID- 1443664 TI - Cystogenesis of the ovarian antral follicle of the rat: ultrastructural changes and hormonal profile following the administration of dehydroepiandrosterone. AB - Immature 27-day-old female Sprague-Dawley rats were administered daily subcutaneous injections of dehydroepiandrosterone (DHEA, 5 mg/100 g BW) to induce the formation of ovarian follicular cysts. Groups of rats were killed on days 0, 10, 15, 20, 25, and 30. Ovaries from each group of rats were processed for light and electron microscopy and for follicular or cystic fluid hormone analysis. Normal antral follicle fluid, PMSG-treated preovulatory follicular fluid, and cystic fluids were analyzed for progesterone (P), estrone (E1), estradiol (E2), testosterone (T), delta 4-androstenedione (delta 4-A), 5 alpha dihydrotestosterone (DHT), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin (PRL). DHEA induced anovulation, acyclicity, and the formation of follicular cysts. In certain antral follicles, there was a dramatic increase in the quantities of smooth endoplasmic reticulum (SER) in the granulosa cells and many mitochondria had tubular cristae. Further depletion of granulosa cell number was associated with intense blebbing of the cytoplasm into the follicle antrum. Formation of the ovarian follicular cyst was completed when the entire cyst was lined by a single layer of transformed granulosa cells in contact via adhering, gap, and tight junctions. These cells had little cytoplasm, mitochondria with lamellar cristae, vast basal and apical bands of microfilaments, and an extensive array of smooth-surfaced endocytotic invaginations on the basal plasma membrane. These endocytotic pits may subsequently form smooth-surfaced vesicles and thereby serve as one mechanism for moving fluid from the ovarian interstitium into the cyst. Theca interna cells were rarely observed in the peripheral regions of the cyst. Abundant smooth muscle cells were located beneath the basement membrane of the epithelial cells comprising the cyst wall. These acquired morphological and physiological features may ensure persistence of the ovarian cyst and thus potentiate a chronic pathological condition. In this study it was also shown that progesterone, estrone, and estradiol as well as androgen concentration increased in the follicle after PMSG treatment. With DHEA treatment, the follicular cystic fluid concentrations of these steroids progressively increased to extremely high levels concurrent with the development of the follicular cysts.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1443665 TI - Changes in histochemical distribution of cell surface heparan sulfate proteoglycan in mouse uterus during the estrous cycle and early pregnancy. AB - We have investigated the changes in immunolocalization of a cell surface heparan sulfate proteoglycan (HSPG) in the mouse uterus during the estrous cycle and at the time of implantation in early pregnancy. A monoclonal antibody prepared against syndecan, a cell surface HSPG from mouse mammary epithelium (gift of Dr. M. Bernfield), was reacted with unfixed and fixed frozen sections of uteri from normally cycling, 3.5 and 4.5 days pregnant, and estradiol-treated immature and ovariectomized mature mice. A polyclonal antibody prepared against basal lamina HSPG from Engelbreth-Holm-Swarm (EHS) tumor cells (gift of Dr. John Hassell) was used as a positive control. The latter showed no variation during the estrous cycle or early pregnancy. Localization of syndecan in uterine epithelium changed from basolateral to predominantly basal as the cycle progressed from metestrus toward estrus. A similar pattern was seen in immature and ovariectomized mature females that had received estradiol injections. With the onset of pregnancy, the basolateral localization became progressively less intense from 3.5 days through 4.5 days of pregnancy. Thus, cell surface HSPG distribution is modulated by hormonally dependent changes in cycling and pregnant mice, supporting previous suggestions that early pregnancy in mice is accompanied by a turnover and rearrangement of uterine epithelial cell surface. PMID- 1443666 TI - Structural analysis of fetal rat lung development. AB - The primary aim of this morphological investigation was to elaborate a concept allowing us to coherently define reference spaces for morphometric analysis of fetal lung development. Beyond this quantitative goal, morphological analysis of cell types, definition of compartments, and reflection about the prospective fate of their constituents provided per se new insights into the developmental processes. Lungs of rat fetuses aged 17-23 days and newborns aged 20 hours were fixed with an osmium tetroxide and glutaraldehyde mixture and their volume determined. Left lungs were embedded in Epon and investigated by light and electron microscopy. The right lung of one animal per group was embedded in methacrylate and step sections obtained to precisely locate the airways within the mesenchyme. The various cell types, their topographical relationships, and their morphological alterations with ongoing development were analyzed with regard to their prospective potentials of differentiation. The developing lung could be partitioned into four zones further subdivided into defined compartments. Zone I forms a superficial mantle around the lobes and the future acini. Consisting of primitive mesenchymal cells, it represents a zone of growth which disappears with the onset of the saccular stage. Zone II is mainly a zone of differentiation. Its interstitium stains intensely due to a dense population of dark cells. Up to gestational day 19, zone II contains future conductive airways with their vessels. After day 21, it comprises the whole prospective gas exchange region. Zones III and IV contain the elements of the airway tree and vascular system, zone IV corresponding to the most proximal generations with an adventitial layer. For all differentiation processes, a centrifugal directionality is manifested. PMID- 1443667 TI - Ultrastructure and immunocytochemistry of the neuroepithelial bodies in the lung of the tiger salamander, Ambystoma tigrinum (Urodela, Amphibia). AB - Light and electron microscopy of the lungs of Ambystoma tigrinum (Urodela) revealed a relatively complex pattern of the neuroendocrine (NE) cells. In the apical parts of smaller septa single NE cells not associated with nerve fibres were covered and surrounded by pneumocytes. The larger septa possessed small areas of ciliated epithelium, in which the NE cells were grouped in a form of neuroepithelial bodies (NEB) consisting of 3-5 cells and covered by goblet cells. NE cells possessed a large nucleus with patches of condensed chromatin, clear cytoplasm, and membrane-bound vesicles of variable morphology and size, containing an electron dense interior surrounded by a lucent space. The size of these dense core vesicles (DCV) ranged from 70-140 nm, while rarely the larger ones exhibited a diameter of 300-600 nm. In some NEB a second type of NE cells was observed for the first time in an amphibian species: these cells communicated with the air space and exhibited on their surface microvilli and a single modified cilium with a 8 + 1 microtubule arrangement. Their cytoplasm contained two types of DCV: dense core granules with a diameter of 140-260 nm and vesicles 320-700 nm in diameter with a moderately electron dense interior. The NEB were associated with intracorpuscular, sensory nerve terminals morphologically afferent and efferent. By immunocytochemistry, the NE cells revealed the presence of serotonin, met-enkephalin, and leu-enkephalin. A paracrine and chemoreceptor role is proposed for NEB of Ambystoma tigrinum. PMID- 1443668 TI - Comparative study of sexual dimorphism of the innominate bone in rodents and amphibians. AB - Sexual dimorphism in the shape of the innominate bone was demonstrated in the rat, mouse, Chinese hamster (Cricetulus griseus), frog (Ranna nigromaculata), and newt (Cynops pyrrhogaster) with a computer-assisted morphometric technique. In the rat, mouse, and hamster, ratios of ischium and pubis widths to the innominate bone length (INL) were larger in the males than in the females; however, the ratio of pubis length to INL was larger in the females than in the males. In the frog, the ratio of distance between the upper edge of the acetabulum and the lower edge of the pubis to INL was larger in males than in females. In the newt, ratios of width of ischiopubis and the longitudinal length of the ischiopubis to INL were larger in females than in males. PMID- 1443669 TI - Lymphoid cells in the harderian gland of the rodent Octodon degus. AB - The Harderian gland of the degu (Octodon degus) is composed of tubulo-alveolar secretory units that share most of morphological features found in the Harderian glands of other rodents. However, a peculiar characteristic observed in the glands of female degus is the existence of lymphoid cell clusters within the connective tissue surrounding the secretory adenomeres. Lymphocytes and lymphoblasts are found associated with blood vessels and especially with nerve bundles in the medullary region of the gland. Occasionally, macrophages and plasma cells are also observed. Although the Golgi apparatus appears well developed, the ultrastructural characteristics of most of these lymphoid elements correspond to those of inactive lymphocytes. Unmyelinated fibers containing clear and dense-core vesicles are found closely related to lymphocytes. On some occasions, lymphocytes present extensive areas of apposition with structures resembling intercellular junctions. The analogy of the lymphoid clusters reported in this study with those described in the avian Harderian gland is discussed. PMID- 1443670 TI - Distribution of p21ras in postimplantation rat embryos. AB - Expression of ras cellular oncogenes during the early postimplantation period in the rat was investigated using immunohistochemistry to p21ras. A broad spectrum polyclonal antibody recognizing N-, Ha- and Ki- forms of p21ras was used in an indirect avidin-biotin-peroxidase (ABC) technique. Positive staining indicating the presence of p21ras was found in embryos from 6.5 to 12 days embryonic age. In early egg cylinders (6.5 days), positive staining for p21ras was observed on the ectoplacental cone, primitive ectoderm and trophectoderm, while primitive endoderm and parietal endoderm appeared paler. In later egg cylinder stages (7.5 days), strong positive staining was observed in the primitive embryonic ectoderm and ectoplacental cone, but parietal and visceral endoderm still appeared to be devoid of positive staining. As development proceeded during primitive streak stages, the visceral and parietal endoderm became positively stained. By 10 days, all tissues appeared to be positive for p21ras, with strong staining appearing in the heart and neural elements. Therefore, p21ras does not appear to be ubiquitous in the rat conceptus prior to gastrulation, but shows differential distribution, appearing later in endodermal derivatives. Possibly p21ras is involved in determination of the ectodermal and endodermal lineages. PMID- 1443671 TI - Localization of extracellular matrix components in developing mouse salivary glands by confocal microscopy. AB - The importance of the extracellular matrix (ECM) in epithelial-mesenchymal interactions in developing organisms is well established. Proteoglycans and interstitial collagens are required for the growth, morphogenesis, and differentiation of epithelial organs and the distribution of these molecules has been described. However, much less is known about other ECM macromolecules in developing epithelial organs. We used confocal microscopy to examine the distribution of laminin, heparan sulfate (BM-1) proteoglycan, fibronectin, and collagen types I, IV, and V, in mouse embryonic salivary glands. Organ rudiments were isolated from gestational day 13 mouse embryos and cultured for 24, 48, or 72 hours. Whole mounts were stained by indirect immunofluorescence and then examined using a Zeiss Laser Scan Microscope. We found that each ECM component examined had a distinct distribution and that the distribution of some molecules varied with culture time. Laminin was mainly restricted to the basement membrane. BM-1 proteoglycan was concentrated in the basement membrane and also formed a fine network throughout the mesenchyme. Type IV collagen was mainly located in the basement membrane of the epithelium, but it was also present throughout the mesenchyme. Type V collagen was distributed throughout the mesenchyme at 24 hours, but at 48 hours was principally located in the basement membrane. Type I collagen was distributed throughout the mesenchyme at all culture times, and accumulated in the clefts and particularly at the epithelial-mesenchymal interface as time in culture increased. Fibronectin was observed throughout the mesenchyme at all times. PMID- 1443672 TI - Hemizona assay and its impact on the identification and treatment of human sperm dysfunctions. AB - The HZA, a functional test for human gamete interaction, has become a useful and valuable experimental tool for physiological and cellular analysis of the early events leading to fertilization. The analysis of the conventional semen parameters with emphasis on sperm morphology (as judged by strict criteria) and motion characteristics (evaluated by computer assisted analysis) constitutes the first obligatory step for a critical evaluation of male-factor patients. Patients in whom fertilization disorders are suspected should be evaluated through bioassays of sperm function of established accuracy. The HZA, a bioassay of sperm zona binding capacity is here proven to be highly predictive of IVF outcome. Ultimately, our increasing knowledge of sperm biology and dysfunction will provide a basis for a better diagnosis (membrane receptor defects and metabolic/biochemical abnormalities?) as well as better therapeutic interventions in patients with sperm disorders. It seems likely that the HZA may be eventually replaced by a standardized test kit in which recombinant human DNA-derived zona receptors mimic the natural function of the hemizonae currently used. This ZP3 reagent may also be a useful antigen for contraceptive development. The HZA therefore constitutes a useful adjuvant in the armentarium for the diagnosis and therapy of male-factor patients. PMID- 1443673 TI - Evaluation of bovine cervical mucus penetration as a test of human spermatozoal function for an in vitro fertilization programme. AB - Thirty-two couples participating in an in vitro fertilization (IVF) programme were evaluated as regards the prognostic value on fertilization of spermatozoal performance through flat capillary tubes filled with standardized midcycle bovine cervical mucus (Penetrak, Serono Diagnostics, Surrey, UK). A statistically significant correlation (P < 0.033) was observed between the distance travelled by the neat spermatozoa in the mucus and the % penetration of oocytes at IVF. There were also significant correlations between motility and progression (P < 0.004) and a borderline correlation between progression and the Penetrak results (P < 0.098). There was no significant difference between the Penetrak distances travelled between the 9 who conceived (33.4 mm) and the 23 who did not (29.9 mm). While the test does add to the knowledge of fertilization potential, the results extrapolated to a larger series would give false positive rates of 25% and false negative rates of 11%. The absence of a clear end point renders the Penetrak mucus penetration test insufficiently accurate to be used as a main measure of the male factor when advising for or against IVF therapy. PMID- 1443674 TI - Comparison of semen analysis between the two Hamilton-Thorn semen analysers. AB - This study was designed to assess the reproducibility of the computer-assisted semen analysis (CASA) system. Semen specimens from 41 suspected subfertile patients were analysed on two identical Hamilton-Thorn Motility analysers (HTM, model 2030, version 7). Specimens were analysed after liquefaction at 37 degrees C for 30 min on two HTMs adjusted to the same gate settings and by using the same semen droplet loaded on a Makler counting chamber prewarmed at 37 degrees C. Significant differences were seen in the total sperm count (P < 0.0004), motile sperm count (P < 0.004), amplitude of lateral head displacement (P < 0.0001), linearity (P < 0.01), and beat cross frequency (P < 0.0001) between the two HTMs. No significant differences between the two machines was seen in the case of other sperm motion parameters: percentage motility, average path velocity, straightline velocity, curvilinear velocity, straightness, and progressive motility. Our results indicate that the reproducibility of several semen parameters analysed by HTM is poor, and steps to remedy this problem are necessary. PMID- 1443675 TI - Effect of multiple centrifugations on the evaluation of the acrosome reaction in human spermatozoa. AB - This study was undertaken to assess the effect of multiple centrifugations on the human acrosome reaction and in vitro fertilizing ability. Semen samples were obtained from sperm donors and from patients participating in our in vitro fertilization programme. Measured sperm samples were centrifuged twice (400xg for 5 min) before or after the induction of the acrosome reaction with calcium ionophore A23187 and before the insemination of oocytes. The samples obtained from the sperm donors were used to measure the acrosomal loss by means of indirect immunofluorescence (T6 monoclonal antibody) and the patient samples were used to assess fertilizing ability and cleavage. Samples centrifuged twice before the chemical induction of the acrosome reaction exhibited significantly elevated levels of acrosomal loss (mean = 46%) as compared to the controls (23%). However, the fertilization (P = 0.688) and cleavage (P = 0.187) rates were not significantly different between the controls and the centrifuged samples. The present study has shown that the centrifugation of motility enriched (swim-up) samples may also modify the acrosomal membrane complex, without compromising fertilizing potential. PMID- 1443676 TI - On the glandular origin of seminal plasma lipids in man. AB - The aim of this study is to examine the glandular origin of seminal fluid lipids in man. The triglycerides, the total cholesterol, the non-esterified fatty acid and the total phospholipids were measured in seminal plasma of vasectomized patients (n = 8) and control subjects (n = 15). The same parameters were measured in seminal plasma collected in three fractions from split ejaculates (n = 10). The total cholesterol and the non-esterified fatty acid are principally prostatic in origin. The phospholipids are secreted by the epididymis but also by the prostate. The origin of the triglycerides seems to be very varied. PMID- 1443677 TI - Andrological study of an intersex ram. AB - An anatomic, histologic, and cytogenetic study was carried out on a young single born ram of 'Bergamasca' breed. At an anatomical level the subject, with anomalous presence of horns adherent to the head, presented hypoplastic testicles descended in two distinct scrotal sacs, hypospadias and small penioid body. The histopathologic analysis showed atrophy of the testicular parenchyma while at a cytogenetic level, sexual chromosome mosaicism was found with XX and XY cells, both at lymphocytic (73%-54, XX; 27%-54, XY) and fibroblastic level. Therefore this finding cannot be explained simply referring to freemartinism. PMID- 1443678 TI - Morphometric and ultrastructural studies on the rat testis following administration of antiserum to human seminal plasma inhibin. AB - A study was undertaken to see the effects of antiserum to human seminal plasma inhibin (hSPI) on the morphology of rat testis. Morphometric, light microscopic, and ultrastructural studies were done on rat testis after 4, 8, and 12 weeks of administration of antiserum to hSPI. Daily sperm production rate was also estimated by histometric method. The light microscopic analysis showed a slight decrease in tubular diameter which was not significant. The degenerative changes in the tubules were marked after 12 weeks of treatment. The daily sperm production rate was reduced by 50% after 12 weeks of treatment. The ultrastructural study revealed phagocytosis of elongated spermatids and spermatozoa enclosed in a vacuole surrounded by Sertoli cells. The Sertoli cells were dedifferentiated into an immature type. The spermatogonia were not affected. The treatment with antiserum to hSPI alters testicular morphology at the spermatid and mature spermatozoa level. Since treatment with AshSPI is known to elevate the FSH level it appears that the morphological changes correlate with the endocrine status. PMID- 1443679 TI - Hemodynamic and organ blood flow responses to halothane and sevoflurane anesthesia during spontaneous ventilation. AB - This study compared systemic hemodynamic and organ blood flow responses to equipotent concentrations of halothane and sevoflurane during spontaneous ventilation in the rat. The MAC values for halothane and sevoflurane were determined. Cardiac output and organ blood flows were measured using radiolabeled microspheres. Measurements were obtained in awake rats (control values) and at 1.0 MAC halothane or sevoflurane. The MAC values (mean +/- SEM) for halothane and sevoflurane were 1.10% +/- 0.05% and 2.40% +/- 0.05%, respectively. The PaCO2 increased to a similar extent in both groups compared with control values. During halothane anesthesia, heart rate decreased by 12% (P < 0.01), cardiac index by 26% (P < 0.01), and mean arterial blood pressure by 18% (P < 0.01) compared with control values. Stroke volume index and systemic vascular resistance did not change. During sevoflurane anesthesia, hemodynamic variables remained unchanged compared with control values. Coronary blood flow decreased by 21% (P < 0.01) and renal blood flow by 18% (P < 0.01) at 1.0 MAC halothane, whereas both remained unchanged at 1.0 MAC sevoflurane. Cerebral blood flow increased to a greater extent with halothane (63%; P < 0.01) than with sevoflurane (35%; P < 0.05). During halothane anesthesia, hepatic arterial blood flow increased by 48% (P < 0.01), whereas portal tributary blood flow decreased by 28% (P < 0.01). During sevoflurane anesthesia, hepatic arterial blood flow increased by 70% (P < 0.01) without a concomitant reduction in portal tributary blood flow. Total liver blood flow decreased only with halothane (16%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443680 TI - Halothane enhances pulmonary artery endothelial eicosanoid release. AB - To determine whether anesthetics alter endothelial eicosanoid release, cultured bovine pulmonary artery endothelial cells were studied during constant flow and pressure perfusion at two oxygen tensions (hypoxia, 50 +/- 2 mm Hg; normoxia, 144 +/- 5 mm Hg; mean +/- SEM) with and without 1% halothane. Endothelialized microcarriers containing approximately 5 x 10(6) cells were loaded into cartridges and perfused (3 mL/min) with Krebs' solution (pH 7.4, at 37 degrees C) equilibrated with each gas mixture. Eicosanoids (6-keto prostaglandin F1 alpha, thromboxane B2, and total peptidoleukotrienes [C4, D4, E4, F4]) were measured by radioimmunoassay and quantified per gram of cellular protein per minute. Eicosanoid release did not vary over time. The 6-keto prostaglandin F1 alpha release increased during hypoxia (normoxia 291 +/- 27 vs hypoxia 395 +/- 35 ng.min-1 x g protein-1; P < 0.01). Halothane (H) increased release of each eicosanoid during both normoxia and hypoxia: 6-keto prostaglandin F1 alpha normoxia 291 +/- 27 versus normoxia + H 356 +/- 32 ng.min-1 x g protein-1, hypoxia 395 +/- 35 versus hypoxia + H 464 +/- 40 ng.min-1 x g protein-1, P < 0.05; thromboxane B2-normoxia 19 +/- 2 versus normoxia + H26 +/- 2 ng.min-1 x g protein-1, hypoxia 20 +/- 2 versus hypoxia + H 38 +/- 5 ng.min-1 x g protein-1, P < 0.001; leukotriene-normoxia 363 +/- 35 versus normoxia + H 489 +/- 52 ng.min-1 x g protein-1, hypoxia 329 +/- 29 versus hypoxia + H 455 +/- 39 ng.min-1 x g protein-1, P = 0.001.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443681 TI - Acute toxic delirium in a patient using transdermal fentanyl. PMID- 1443682 TI - Electroencephalographic monitoring of cerebral function during asystole and successful cardiopulmonary resuscitation. PMID- 1443683 TI - Chiari I malformation presenting as recurrent spinal headache. PMID- 1443684 TI - Acute respiratory failure in a patient with acute leukemia undergoing minor surgery. PMID- 1443685 TI - Change of ectopic supraventricular tachycardia to sinus rhythm during administration of propofol. PMID- 1443686 TI - Epidural anesthesia in a parturient patient with congenital absence of the inferior vena cava. PMID- 1443687 TI - Glossopharyngeal nerve block for carotid sinus syndrome. PMID- 1443688 TI - Dorsal primary ramus nerve block for treatment of low back pain after epidural analgesia. PMID- 1443689 TI - Continuous stellate ganglion blockade for reflex sympathetic dystrophy. PMID- 1443690 TI - Oculopharyngeal dystrophy: an approach to anesthetic management. PMID- 1443691 TI - Bilateral interpleural injection of lidocaine after bilateral lung surgery through median sternotomy in four patients. PMID- 1443692 TI - A fractured epidural needle: case report and study. PMID- 1443693 TI - Extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation is still a relatively new technology that has recently achieved recognition after initial clinical disappointment in the late 1970s. At present, it is considered standard therapy for the full-term infant with PPHN who fails CMV and extraordinary, heroic therapy for older children and adults with ARF or cardiac failure, or both. Currently, the emphasis is on developing new technologies for increasing safety and effectiveness. Areas of interest include heparinless circuits, carotid artery reconstruction, improved monitoring, and expanding applications of VV ECMO. As ECMO becomes safer and more effective, it is believed that new and expanding patient populations will emerge to include premature infants, earlier intervention in term infants, and more liberal application to pediatric and adult populations. PMID- 1443694 TI - Local anesthetic-sensitive electrodes: preparation of coated-wire electrodes and their basic properties in vitro. AB - Coated-wire electrodes with local anesthetic (LA) cation-selective membranes were prepared, and their properties in vitro were investigated. Copper wires (0.8-mm diameter) were coated with gel membranes of 110 mg of poly(vinyl chloride), 5 mg of ion pairs of tetraphenylborate anion with LA cation, 100 mg of dioctylphtalate, and 1.5 mL of tetrahydrofuran. This was the composition determined to be most suitable. Their electromotive force relative to an Ag/AgCl electrode was measured in LA solutions. The lidocaine, dibucaine, and mepivacaine electrodes all showed good Nernstian response at 25 degrees C in aqueous solutions in the concentration ranges of 1 x 10(-4) to 1 x 10(-2) mol/L, 4 x 10( 5) to 1 x 10(-2) mol/L, and 5 x 10(-5) to 1 x 10(-2) mol/L, respectively. The response time was within 10 s. The electrode potential decreased as the pH in the solution increased, with a corresponding decrease of the protonated form of LA. The hydrophobic nature of the LA was closely related to the electromotive force and to the selectivity of the electrode toward various LA cations. Dibucaine, the most hydrophobic, had the highest electrode potential. The more hydrophobic the LA of the electrode, the less it is interfered with by other LA molecules. The more hydrophobic the interferent cation, the more it acts on the electrode potential. The electrode system could also measure LA in human plasma at 37 degrees C, although the responsiveness was depressed in the low concentration range owing to binding of LA to the serum protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443695 TI - The genioglossus muscle belongs not to inspiratory but to expiratory muscle? PMID- 1443696 TI - Intravenous halothane--questions remain. PMID- 1443697 TI - Removal of a tenacious epidural catheter. PMID- 1443698 TI - Cyclosporine A and cardiopulmonary bypass. PMID- 1443699 TI - Touchscreen technology: potential source of cross-infections. PMID- 1443700 TI - Laryngeal mask airway in cervical spine injuries. PMID- 1443701 TI - Epidural kits: incompatible contents. PMID- 1443702 TI - Is your scavenger system functional? PMID- 1443703 TI - Package inserts and other dosage guidelines are especially useful with new analgesics and new analgesic delivery systems. PMID- 1443704 TI - Propofol requirements for induction of anesthesia in children of different age groups. AB - To demonstrate any age-related differences in propofol requirements for induction of anesthesia, 150 healthy children aged 3-5 yr (n = 50), 6-9 yr (n = 50), and 10 15 yr (n = 50) scheduled for outpatient surgery were randomly assigned to receive an induction dose of propofol of 1.5, 2.0, 2.5, 3.0, or 3.5 mg/kg. To limit pain during injection, alfentanil (5 micrograms/kg) was administered before the propofol. Patients were classified as asleep or not asleep 30 s after the propofol. Incidence of excitation, injection pain, and apnea during induction of anesthesia were noted; arterial blood pressure and heart rate were recorded for 5 min after induction. More than 95% of the children were asleep in the dose groups receiving > or = 2.5 mg/kg. The number of patients falling asleep after receiving 1.5 mg/kg of propofol increased significantly with increasing age (P < 0.05); the difference between the oldest and the youngest age groups was the most significant (P < 0.05). Significant decreases in mean arterial blood pressure and heart rate occurred after induction in all dose and age groups without any systematic intergroup differences. Apnea occurred more frequently in older children (P < 0.01) and with larger doses (P < 0.01). The most frequent side effect was erythema near the site of injection, and its occurrence was dose dependent. The authors conclude that 2.5 mg/kg of propofol, if preceded by 5 micrograms/kg of alfentanil, is an appropriate induction dose for children aged 3 15 yr and that the sleep response to 1.5 mg/kg is more in older children. PMID- 1443705 TI - Effectiveness of preoperative sedation with rectal midazolam, ketamine, or their combination in young children. AB - To determine which of three types of rectal sedation was most effective preoperatively in facilitating parental separation and intravenous cannulation in young children, 100 children 3.0 +/- 1.7 (mean +/- SD) yr of age were randomly assigned to four equal groups. One group (M-K-A) received rectal midazolam (0.5 mg/kg), ketamine (3 mg/kg), and atropine (0.02 mg/kg). The other sedation groups received the same doses of midazolam and atropine (M-A) or ketamine and atropine (K-A) alone, and the control group (A) received only rectal atropine. Most children in either the M-K-A (100%) or M-A (92%) groups separated easily from their parents without struggling or crying, significantly more than in the K-A (60%) or A (64%) groups. However, more children in the M-K-A group (44%) were asleep during separation than in the M-A group (8%; P < 0.05). Only 20% of the children in the M-A or M-K-A groups cried during intravenous catheter placement, significantly less than in the K-A (56%) or A (92%) groups. Intravenous catheter placement was also successful significantly more often in the M-A (80%) and M-K-A (84%) groups than in the K-A (48%) or A (40%) groups. Complications were similar among the groups, but there was evidence that midazolam prolonged recovery time in some patients. Rectal midazolam with or without ketamine is a useful technique when intravenous catheter placement before induction of anesthesia is desired. PMID- 1443706 TI - Plasma lidocaine concentrations during epidural blockade with isoflurane or halothane anesthesia. AB - Because isoflurane maintains hepatic blood flow at higher flows than halothane, we proposed that the elimination of lidocaine would be different between these two volatile anesthetics. The plasma lidocaine concentrations were determined in 14 female patients undergoing epidural blockade plus isoflurane anesthesia and compared with those obtained during halothane anesthesia for lower abdominal surgery. General anesthesia was maintained with isoflurane (0.46% +/- 0.04% [mean +/- SE] inspired, n = 7) or halothane (0.48% +/- 0.05% inspired, n = 7) and 67% nitrous oxide in oxygen. All patients received 2% lidocaine solution, 10 mL as a bolus dose and continuous administration at a rate of 10 mL/h, through the epidural catheter. The plasma lidocaine concentrations over 180 min after the epidural injection in patients receiving isoflurane were similar to those in patients receiving halothane. The results suggest that low inspired concentrations of isoflurane do not reduce plasma lidocaine concentrations in patients during epidural blockade, compared with halothane. PMID- 1443707 TI - A rat sciatic nerve model for independent assessment of sensory and motor block induced by local anesthetics. AB - The purpose of this study was to develop a reliable model to independently quantify motor and sensory block produced by local anesthetics. The sciatic nerve was blocked in 52 rats by injecting 0.2 mL of 0.125%, 0.25%, 0.5%, or 0.75% bupivacaine (n = 13 for each concentration). Accurate needle placement was achieved using a nerve stimulator at 0.2 mA and 1 Hz. Ten control rats received 0.9% saline (n = 5) or sham nerve stimulation (n = 5). Motor block was assessed by measuring hindpaw grip strength with a dynamometer. Sensory block was determined by measuring hindpaw withdrawal latency from radiant heat. The intensity of both motor and sensory block measured at 30-min intervals was plotted against time until full recovery to obtain the area under the curve. Intergroup comparisons using analysis of variance showed increasing area under the curve with increasing concentrations of bupivacaine for motor blocks (P < 0.05 for all intergroup comparisons except 0.5% vs 0.75%) and sensory blocks (P < 0.05 for all intergroup comparisons). Normal saline or sham nerve stimulation did not result in any motor or sensory block. PMID- 1443708 TI - Lumbar subarachnoid ethylenediaminetetraacetate induces hindlimb tetanic contractions in rats: prevention by CaCl2 pretreatment; observation of spinal nerve root degeneration. AB - Disodium ethylenediaminetetraacetate (Na2EDTA) has replaced sodium bisulfite as the antioxidant in 2-chloroprocaine, Nesacaine CE. This study was undertaken to determine whether this new formulation has neurotoxic effects when administered in the subarachnoid space. Sprague-Dawley rats receiving subarachnoid injections of 1.5 mM or higher concentrations of Na2EDTA immediately initiated a circling behavior that was followed by the development of tetanic contractions of the hindlimbs lasting for 15-20 min. The tetanic contractions were followed by a brief period of hindlimb paralysis. Pretreatment of rats by subarachnoid injections of 1 mM CaCl2 prevented the development of tetanic contractions and paralysis of the hindlimb. Histologic examination of animals receiving Na2EDTA revealed moderate to severe focal degenerative changes in spinal nerve roots. Control rats receiving subarachnoid injections of normal saline solution did not develop tetanic contraction nor pathological changes on light microscopy. These results suggest that the preservative used in Nesacaine-MPF may be neurotoxic. PMID- 1443709 TI - Prolongation of epidural anesthesia using a lipid drug carrier with procaine, lidocaine, and tetracaine. AB - This study evaluated the effect of a lipid drug carrier (iophendylate) on epidural anesthesia. The intensity and duration of motor blockade produced by aqueous and lipid preparations of local anesthetics were assessed in rabbits with long-term indwelling catheters in the epidural space. Motor blockades produced by procaine (1%, 2%, and 4%), lidocaine (1%, 2%, and 4%), and tetracaine (0.5%, 1%, and 2%) in normal saline solution were compared with the effects produced by equimolar amounts of the drug solutions in iophendylate. Procaine (4%) in aqueous solution produced motor blockade lasting 30 +/- 3.54 min (mean +/- SD) versus 84 +/- 4.18 min in lipid solution. Lidocaine (2% and 4%) in aqueous solution produced motor blockade lasting 41 +/- 4.18 and 65 +/- 6.12 min versus 39 +/- 4.18 and 118 +/- 10.1 min, respectively, in lipid solution. Aqueous tetracaine (0.5%, 1%, and 2%) produced motor blockade of 106 +/- 9.62, 189 +/- 6.52, and 273 +/- 26.8 min versus 284 +/- 14.7, 335 +/- 15.8, and 365 +/- 26.9 min, respectively, in their lipid counterparts. A control group of animals that received normal saline solution or iophendylate alone did not exhibit motor blockade. These results may be attributed to sustained release of local anesthetics from the lipid vehicle. Hence, lipid drug carriers may be effective in prolonging epidural anesthesia. PMID- 1443710 TI - Subblocking concentrations of local anesthetics: effects on impulse generation and conduction in single myelinated sciatic nerve axons in frog. AB - Phenomena seen in axons exposed to subblocking doses serve as the basis for interpreting clinical and behavioral observations during onset and recovery of peripheral nerve block. To delineate the changes in excitability and in impulse conduction caused by subblocking concentrations of local anesthetics (LAs) in myelinated peripheral nerve fibers, LAs were applied to excised frog sciatic nerves while impulse conduction was monitored in single axons. For concentrations ranging from 0.01 to 1.2 times the LA concentration needed to block impulse conduction, three measures of susceptibility to LA were made to quantify the action of the drugs on "resting" fibers (firing rates < or = 0.5 Hz): the increase in the threshold for electrical activation of impulses, the increase in conduction latency reflecting the slowing of impulse conduction in the region exposed to LA, and the "critical blocking concentration" of LA just sufficient to prevent impulse conduction in the recorded fiber. Wide interfiber variation in these variables was observed (e.g., for lidocaine, latency increases at block ranged from 66% to 257% of control, blocking concentrations ranged from 0.29 to 1.40 mM), which was not correlated with fiber diameter (as indicated by resting conduction velocity). Mathematical modeling of impulse conduction in fibers exposed to LA demonstrated that the interfiber variation in susceptibility to LA block could result from interfiber differences in the density of sodium and potassium channels. The effects of LA were also studied in active fibers (firing rates > 0.5 Hz). Local anesthetics reversibly inhibited two normally occurring afteroscillations in membrane threshold related to afterpotentials following an impulse. These were "superexcitability," a transient lowering of threshold lasting as long as 1 s, and "depression," a phase of raised threshold peaking within 2-4 s after an impulse and recovering slowly over several minutes. Impulse activity also transiently increased the apparent potency of LAs. Such "use dependent" increases in threshold and decreases in conduction velocity showed kinetics that were agent specific, lasting 1 s after a burst of impulses for lidocaine and lasting > 10 s for bupivacaine. At low concentrations, within the range of nontoxic plasma concentrations after systemic administration, the predominant actions of LAs on conducting fibers were transient decreases in excitability and conduction velocity in combination with a reduction of intrinsic oscillatory aftereffects of impulse discharge. These effects may degrade decoding of information in discharge patterns without actually blocking conduction of infrequent impulses, suggesting how functional blockade of coordinated movement and perception may occur even without complete blockade of impulse conduction. PMID- 1443711 TI - Central nervous system toxicity of local anesthetic mixtures in the rat. AB - Local anesthetics are often administered as mixtures during regional anesthesia. This study investigated whether a synergistic or antagonistic interaction between amide/amide or amide/ester local anesthetic combinations is present with respect to central nervous system toxicity. For surgical preparation, rats were anesthetized with 0.8% halothane in 30% O2/balance N2O and mechanically ventilated. Mean arterial blood pressure and the electroencephalogram were continuously monitored. After surgery, the halothane was discontinued for 15 min. An intravenous infusion of solutions containing lidocaine alone, bupivacaine alone, or any of three mixtures of the two drugs was then begun and continued at a fixed rate until seizure activity was observed on the electroencephalogram. Total administered doses of both drugs were compared by isobolographic analysis. After a similar protocol, a second experiment was performed evaluating lidocaine, tetracaine, or any of three mixtures of those two drugs. In both experiments, normocapnia, normoxia, and normothermia were maintained for all rats. For mixtures of lidocaine/bupivacaine (P = 0.40) and lidocaine/tetracaine (P = 0.24), there was no evidence that a significant degree of either synergism or antagonism was present. At the onset of seizures, mean arterial pressure was lowest in the lidocaine-alone groups in both experiments. Increasing doses of either bupivacaine or tetracaine (with correspondingly decreasing doses of lidocaine) were associated with greater mean arterial pressure values at onset of seizures. We conclude that central nervous system toxic effects of amide/amide or amide/ester anesthetic combinations, such as might occur during accidental intravascular injection, are no more than when the drugs are administered alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443712 TI - Locomotor activity after recovery from hypnosis: midazolam-morphine versus midazolam. AB - This study was performed to test the hypothesis that sedation after recovery from pharmacologic hypnosis is less pronounced if hypnosis is induced with a midazolam morphine combination compared with midazolam administered alone. Loss of the righting reflex was used as an index for the hypnotic effect and reduction of locomotor activity as an index for the sedative effect. One group of rats received midazolam (20 mg/kg i.v) and another group an equipotent (in relation to the hypnotic ef.fect) combination of midazolam (4 mg/kg i.v.) and morphine (1.3 mg/kg i.v.). The duration of loss of the righting reflex in the midazolam and midazolam-morphine groups was 30 +/- 3 and 28 +/- 2 min, respectively (mean +/- SE). The difference between the groups in locomotor activity after recovery from hypnosis was very pronounced. The locomotor activity in the midazolam-morphine group at 1 and 2 h was seven and five times greater, respectively, than in the midazolam group (P < 0.005). The profound difference in locomotor activity for the two treatment groups was explained on the basis of the difference in the outcomes of midazolam-morphine interactions with regard to hypnosis (synergism) and sedation (summation). When the animals recovered from hypnosis, the synergism of the drug interaction ceased to be a contributing factor. PMID- 1443713 TI - Thermoregulatory vasoconstriction during propofol/nitrous oxide anesthesia in humans: threshold and oxyhemoglobin saturation. AB - To determine the thermoregulatory effects of propofol and nitrous oxide, we measured the threshold for peripheral vasoconstriction in seven volunteers over a total of 13 study days. We also evaluated the effect of vasoconstriction on oxyhemoglobin saturation (SpO2). Anesthesia was induced with an intravenous bolus dose of propofol (2 mg/kg), followed by an infusion of 180 micrograms.kg-1 x min 1 for 15 min, and maintained with 60% nitrous oxide and propofol (80-160 micrograms.kg-1 x min-1). Central and skin surface temperatures and SpO2 (using two different pulse oximeters) were measured continuously; plasma propofol concentrations and arterial PO2 were measured at 15-min intervals. Volunteers were cooled with a circulating water blanket until definitive peripheral vasoconstriction was detected. The tympanic membrane temperature triggering vasoconstriction was considered the thermoregulatory threshold. Vasoconstriction developed on seven study days during propofol/nitrous oxide anesthesia at a central temperature of 33.3 +/- 1.0 degrees C (mean +/- SD) and plasma propofol concentration of 3.9 +/- 1.1 micrograms/mL. The thresholds during anesthesia were significantly lower than those during the control period (36.7 +/- 0.3 degrees C), but the correlation between plasma propofol concentrations and vasoconstriction thresholds was poor. On the remaining six study days, vasoconstriction did not develop despite central temperatures ranging from 32.1 to 32.7 degrees C. Corresponding propofol concentrations were 4.1-10.9 micrograms/mL. These data suggest that anesthesia with propofol, in typical clinical concentrations, and 60% nitrous oxide substantially inhibits thermoregulatory vasoconstriction. Vasoconstriction increased SpO2 by approximately 2% without a significant concomitant change in PO2. The observed increase in SpO2 probably reflects decreased transmission of arterial pulsations to venous blood in the finger. PMID- 1443714 TI - Alfentanil-induced hypermetabolism, seizure, and histopathology in rat brain. AB - We evaluated the effect of alfentanil on hippocampal glucose utilization and histopathology associated with alfentanil-induced seizures. Three separate experiments were performed. First, anesthetized, paralyzed Long-Evans rats (n = 15; 5 rats per group) were mechanically ventilated and randomly assigned to three groups: (a) control, 70% N2O and 30% O2 continued for 1 h; (b) low-dose alfentanil (150 micrograms/kg i.v. bolus), followed by infusion at 15 micrograms.kg-1 x min-1 for 1 h without N2O; or (c) high-dose alfentanil (1000 micrograms/kg i.v. bolus), followed by infusion at 100 micrograms.kg-1 x min-1 for 1 h without N2O. After 1 h, [6-14C]glucose was injected intravenously for autoradiography. With high-dose alfentanil, there was increased glucose utilization in the ventral hippocampus and the lateral septal nucleus. In the second experiment, anesthetized, paralyzed Sprague-Dawley rats (n = 12; 4 rats per group) were mechanically ventilated, underwent insertion of hippocampal depth electrodes, and were randomly assigned to three groups: (a) control, 70% N2O and 30% O2; (b) low-dose alfentanil (150 micrograms/kg i.v. bolus), with 70% N2O and 30% O2; or (c) high-dose alfentanil (1000 micrograms/kg i.v. bolus), with 70% N2O and 30% O2. An epileptiform pattern was observed on hippocampal and subdermal electroencephalographic recordings in both alfentanil groups. In the third experiment, anesthetized, paralyzed Sprague-Dawley rats (n = 20) were mechanically ventilated and assigned to two groups: (a) control, 70% N2O and 30% O2 (n = 5) or 100% O2 (n = 5) continued for 1 h; or (b) alfentanil (2000 micrograms/kg i.v. bolus), followed by infusion at 33.3 micrograms.kg-1 x min-1 for 1 h with 100% O2. After tracheal extubation, the rats recovered overnight. Light-microscopic evaluation revealed hippocampal or amygdaloid damage in 6 of the 10 alfentanil-treated rats. High doses of alfentanil administered to rats can produce limbic system seizure activity with hypermetabolism associated with neuropathologic lesions. PMID- 1443715 TI - Time-course of respiratory depression after an alfentanil infusion-based anesthetic. AB - Postoperative respiratory depression after alfentanil administration has been described in several case reports. The effects of a prolonged alfentanil infusion on the CO2 response curve or cognitive function have not been studied. Twenty-one ASA physical status I or II patients were studied after a prolonged alfentanil infusion (> 90 min) to determine the incidence of postoperative respiratory depression, arterial O2 desaturation, and impairment of cognitive function. Each patient's recovery was observed at 30-min intervals for evidence of respiratory depression (utilizing the Read CO2 rebreathing method), desaturation by pulse oximetry (severe desaturation defined as arterial O2 saturation < 90%), and cognitive function (utilizing Trieger dot and digit substitution tests). Plasma samples were also examined for secondary elevations in alfentanil plasma concentrations. Significant depression of the CO2 response curve and cognitive function was found up to 1 h postoperatively. Arterial O2 desaturation was seen in 11 of 21 patients (52%). No correlation was found between arterial O2 desaturation and cognitive function scores or CO2 rebreathing results. Increased depression of the CO2 response curve was not necessarily associated with severe desaturation episodes. A secondary increase in plasma alfentanil concentration was detected in 5 of the 21 patients (24%), but these patients did not experience further depression of the CO2 response curve. We conclude that prolonged alfentanil administration may result in severe arterial O2 desaturation with significant depression of the hypercapnic respiratory drive during the first hour in the postanesthesia care unit, even though the majority of our patients were easily aroused in response to verbal stimuli. PMID- 1443716 TI - R-phenylisopropyl-adenosine increases spinal cord blood flow after intrathecal injection in the rat. AB - The A1-adenosine receptor agonist, R-phenylisopropyl-adenosine (R-PIA), demonstrated antinociceptive properties in animal studies after intrathecal administration. In the evaluation of a drug for possible spinal injection in humans, the effects of intrathecal R-PIA on spinal cord blood flow (SCBF) were investigated using the laser-Doppler flow-metry technique in anesthetized rats. In low doses (0.1-1 nmol), no change in SCBF was recorded, whereas larger doses (10-100 nmol) caused a significant increase in SCBF. No change in systemic arterial blood pressure could be seen, except for a decrease after administration of the largest dose of R-PIA (100 nmol). It is concluded that R-PIA in doses of 10 nmol and larger induces an increase in SCBF after intrathecal injection in anesthetized rats and that an increase in blood flow is seen before any effect on the systemic circulation is detected. It can also be deduced that the antinociceptive effects of R-PIA after intrathecal injection are not a consequence of spinal ischemia and that disturbances in local blood flow cannot be expected to constitute a neurotoxic factor. PMID- 1443717 TI - Changes in functional residual capacity and regional diaphragm lengths after upper abdominal surgery in anesthetized dogs. AB - The respiratory performance of the diaphragm may be altered by changes in mechanical or neural factors, or both, induced by upper abdominal surgery. We conducted this study to examine the effects of upper abdominal surgery on postoperative respiratory function. We studied resting lengths of four diaphragm regions, three in the costal and one in the crural diaphragm, with biplane video roentgenography in six dogs immediately after upper abdominal surgery and up to 30 days postoperatively. Functional residual capacity was 16.7% smaller immediately after surgery compared with values obtained in the same animals after 30 days. Simultaneously measured resting lengths of each of the diaphragm regions immediately after surgery were longer, on average by 8.3%, than 30 days postoperatively. During the postoperative course, resting diaphragm lengths gradually and uniformly decreased as functional residual capacity increased. Phrenic nerve stimulation in four other dogs immediately after identical surgery resulted in large diaphragm shortening (from 42% to 55%), indicating that neither the diaphragm nor phrenic nerves were injured by the surgical manipulation. We hypothesize that respiratory dysfunction after upper abdominal surgery may be, at least in part, attributed to a decreased central drive for breathing caused by activation of the afferent limb of an inhibitory reflex owing to stretching of the diaphragm. PMID- 1443718 TI - Direct measurement of nitrous oxide MAC and neurologic monitoring in rats during anesthesia under hyperbaric conditions. AB - The minimum alveolar concentration (MAC) of nitrous oxide necessary to prevent purposeful movement in rats has not been directly measured; rather, it has been extrapolated because the required partial pressure exceeds 760 mm Hg, or 1 atm absolute pressure (ATA). Values reported have ranged from 1.36 to 2.20 ATA (136 220 vol%, or 1034-1672 mm Hg). By maintaining general anesthesia at 2.25 ATA (1710 mm Hg), we directly measured the nitrous oxide MAC in 17 Long-Evans rats during mechanical ventilation and monitoring of two-channel electroencephalogram, compressed spectral array and cortical evoked potentials, electrocardiograph, and respiratory and anesthetic gases by mass spectrometry. After a minimal stabilization period of 30 min during ventilation by 1.8 ATA nitrous oxide and 0.45 ATA oxygen, MAC measurements were begun. Each rat was given up to three noxious electrical stimulations of 50 V by 10-ms-duration pulses at 50/s for 45 s. The partial pressure of nitrous oxide was decreased by approximately 10% after each negative response. The MAC was taken as the nitrous oxide concentration midway between that at which there was no response and that at which the rat moved purposefully. The nitrous oxide MAC in Long-Evans rats was determined to be 1.55 +/- 0.16 ATA (mean +/- SD). Hyperbaric nitrous oxide decreased electroencephalogram wave frequency to a predominantly theta rhythm of increased amplitude. Cortical evoked potentials had decreased wave amplitudes and increased latencies with increasing partial pressures > 0.75 ATA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443719 TI - A comparative study of blood warmer performance. AB - Massive transfusions of refrigerator-temperature blood may induce hypothermia and life-threatening arrhythmias; for this reason a variety of devices have been developed for rapid blood warming. Blood warmers available in the United States use one of three warming technologies: dry heat, water bath, or countercurrent heat exchange. In the current study we evaluated blood warmers representative of each technology for speed and extent of heat transfer: the Fenwal blood warmer (Fenwal Laboratories; dry heat), the DW-1000 (American Pharmaseal Co.; dry heat), the FloTem IIe (DataChem Inc.; dry heat), the Hemokinetitherm (Dupaco Inc.; water bath), and the H250 and H500 (Level 1 Technologies; countercurrent heat exchange). Only one countercurrent heat instrument (the H500) was able to heat blood > or = 33 degrees C at target flow rates > or = 250 ml/min. Dry heat and water bath blood warmers were unable to warm blood > or = 33 degrees C at target flow rates > or = 100 ml/min. High resistance to flow with the proprietary tubing required for one instrument (the Hemokinetitherm) prevented tests of blood warming at rates > 150 ml/min. We found that instruments that used countercurrent technology warmed blood and saline more effectively than did blood warmers that used either dry heat or water bath technology. Our study also demonstrated the need for close control and standardization of experimental conditions in the evaluation of blood warming devices. PMID- 1443720 TI - Use of the laryngeal mask for tracheal intubation in patients at increased risk of aspiration of gastric contents. PMID- 1443721 TI - Neuromuscular blockade in a patient with active dermatomyositis. PMID- 1443722 TI - The effect of positive end-expiratory pressure on right-to-left shunting at the atrial level as documented by transesophageal echocardiography. PMID- 1443723 TI - Sexual illusions and propofol sedation. PMID- 1443724 TI - An epidemic of hypoxemia in two intensive care units: cause and human response. PMID- 1443725 TI - Lethal progression of heart block after prosthesis cementing with methylmethacrylate. PMID- 1443726 TI - Unconsciousness and apnea complicating parascalene brachial plexus block: possible subarachnoid block. PMID- 1443727 TI - Development of an acute withdrawal syndrome following the cessation of intrathecal baclofen in a patient with spasticity. PMID- 1443728 TI - Value of the laryngeal mask airway during thoracotomy. PMID- 1443729 TI - High-frequency oscillation may be useful in perioperative respiratory management of neonates with congenital cystic adenomatoid malformation. PMID- 1443730 TI - Memory during anesthesia. PMID- 1443731 TI - Partially paralyzed: a personal experience. PMID- 1443732 TI - Intractable cardiac arrest in children given succinylcholine. PMID- 1443733 TI - A double tube technique of adult fiberoptic assisted tracheal intubation. PMID- 1443734 TI - Laryngeal mask airway. Indications and contraindications. PMID- 1443735 TI - Volotrauma and the intravenous oxygenator in patients with adult respiratory distress syndrome. PMID- 1443736 TI - Use of the laryngeal mask airway as an alternative to a face mask during outpatient arthroscopy. AB - The laryngeal mask airway (LMA) has recently become available in the United States, and several authors have suggested that it is superior to an anesthesia mask. To test this hypothesis, 64 patients undergoing outpatient arthroscopic knee surgery were randomly assigned to have anesthesia maintained via either a laryngeal mask airway (LMA) (n = 31) or a standard face mask (n = 33). Anesthesia was induced with fentanyl 1 microgram.kg-1 and propofol 2 mg.kg-1 and maintained with a variable-rate propofol infusion (50-180 micrograms.kg-1 x min) and nitrous oxide 67% in oxygen. The LMA was inserted without difficulty by inexperienced anesthesiologists in 90% of the patients. Problems associated with airway management were more common in patients in the face mask (control) group. Episodes of hemoglobin oxygen desaturation (< 95%) occurred in 52% of patients in the face mask group compared to only 13% in the LMA group (P < 0.05). Intraoperative airway manipulations were required in 15% of face mask patients (vs. 3% of the LMA group), and difficulties in maintaining an airway were reported by 24% of the resident anesthesiologists caring for patients in the face mask group (vs. none in the LMA group) (P < 0.05). Insertion of the LMA was not associated with any acute changes in hemodynamic values. Intraoperative hemodynamic values and anesthetic requirements did not differ significantly between the two treatment groups. There were no significant differences in the emergence and recovery times or in the incidence of postoperative sore throats between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443737 TI - Clinical trials of an intravenous oxygenator in patients with adult respiratory distress syndrome. AB - In patients with severe adult respiratory distress syndrome, mechanical ventilation may not be able to ensure gas exchange sufficient to sustain life. We report the use of an intravenous oxygenator (IVOX) in five patients who were suffering from severe adult respiratory distress syndrome as a result of aspiration, fat embolism, or pneumonia. IVOX was used in an attempt to provide supplemental transfer of CO2 and O2 and thereby reduce O2 toxicity and barotrauma. All patients were tracheally intubated, sedated, and chemically paralyzed and had a PaO2 < 60 mmHg when the lungs were ventilated with an FIO2 = 1.0 and a positive end expiratory pressure of > or = 5 cmH2O. The right common femoral vein was located surgically, and the patient was systemically anticoagulated with heparin. A hollow introducer tube was inserted into the right common femoral vein, and the furled IVOX was passed into the inferior vena cava and advanced until the tip was in the lower portion of the superior vena cava. IVOX use ranged from 2 h to 4 days. In this group of patients, IVOX gas exchange ranged from 21 to 87 ml x min-1 of CO2 and from 28 to 85 ml x min-1 of O2. One of the five patients survived and was discharged from the hospital. The IVOX transferred up to 28% of metabolic gas-exchange requirements. One patient with a small vena cava showed signs of caval obstruction. Three other patients demonstrated signs of a septic syndrome after the device was inserted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443738 TI - Clonidine reduces sympathetic activity but maintains baroreflex responses in normotensive humans. AB - Clonidine, an alpha 2-adrenergic agonist, has been shown to modify the hemodynamic responses to surgery. To examine further the mechanism underlying this action, we evaluated the neurocirculatory effects of oral clonidine and the ability of clonidine to alter the hemodynamic and sympathetic responses to a noxious stimulus (cold pressor test) and to baroreceptor perturbations in nine healthy men (ages 20-29 yr). Heart rate (ECG), blood pressure (radial artery catheter), central venous pressure (jugular vein), and cardiac output (impedance cardiography) were monitored before and after oral clonidine (0.3 mg) or placebo. Plasma norepinephrine was measured with high-performance liquid chromatography. Sympathetic nerve activity (SNA) to skeletal muscle blood vessels was recorded from a Tungsten needle positioned within the peroneal nerve. Baroreceptor testing was carried out by intravenous bolus injections of nitroprusside (100 micrograms) followed 60 s later by intravenous phenylephrine (150 micrograms). The slope of the linear relationship between the change in R-R interval versus the change in mean pressure (cardiac baroslope) or change in SNA versus change in diastolic pressure (sympathetic baroslope) was determined at baseline and 75 min after clonidine or placebo. In addition, peak responses to the cold pressor test (60-s hand immersion in ice water) were determined at the same intervals. Clonidine progressively decreased blood pressure and muscle SNA over the 75-min session. Clonidine subtly reduced the sympathoexcitation produced by the cold pressor test but did not alter the gain of the baroreceptor reflex regulating cardiac interval or peripheral SNA; baroslope relationships were simply shifted leftward (to operate at lower pressures).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443739 TI - The influence of propofol with and without nitrous oxide on cerebral blood flow velocity and CO2 reactivity in humans. AB - The cerebrovascular response to CO2 has been reported to be preserved during propofol anesthesia, but no comparison with awake control values has been made, and the additional influence of N2O has not been investigated. Using the noninvasive technique of transcranial Doppler ultrasonography, this study investigated the cerebrovascular response to varying levels of PaCO2 while awake and during anesthesia with propofol and propofol/N2O. Seven adults without systemic diseases undergoing nonneurologic surgery were studied. A pulsed-wave Doppler monitor was used to measure the mean middle cerebral artery flow velocity (Vmca) during varying levels of PaCO2 (25-55 mmHg) under the following conditions: 1) awake; 2) propofol 2.5 mg.kg-1 bolus followed by continuous infusion of 150 micrograms.kg-1.min-1; and 3) propofol as in the condition above plus 70% N2O. During the awake study condition, hypocapnia was induced by voluntary hyperventilation, and hypercapnia was induced with rebreathing of 7% CO2 in a closed circuit. During the anesthetized study conditions, hypocapnia and hypercapnia were induced by adjustment of minute ventilation. A minimum of five to six simultaneous Vmca and PaCO2 measurements were obtained under each of the study conditions. Systemic blood pressure was monitored via a radial arterial catheter, and phenylephrine was administered if mean arterial blood pressure decreased below 60 mmHg (phenylephrine was used in three of five patients in the propofol-N2O group). Linear regression and analysis of covariance were used for statistical analysis of Vmca-PaCO2 relationships.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443740 TI - Inhaled nitric oxide after mitral valve replacement in patients with chronic pulmonary artery hypertension. AB - Patients with mitral valve disease can develop pulmonary artery hypertension that persists after mitral valve replacement. In 1987, nitric oxide (NO) was reported to be an important factor accounting for the biologic activity of endothelium derived relaxing factor. Inhaled NO was subsequently reported to be a selective pulmonary vasodilator in animals and patients. Therefore we investigated the vasodilating effect of inhaled NO in patients with mild pulmonary artery hypertension after mitral valve replacement. Six patients who underwent mitral valve replacement for mitral stenosis presented with a mean pulmonary artery pressure greater than 25 mmHg within 24 h after surgery. During mechanical ventilation at FIO2 0.5, NO (36.8-38.4 ppm) was breathed for 10 min. Hemodynamic data were recorded before NO, after 10 min of NO inhalation, and 30 min after the end of NO inhalation. Statistically significant (P < 0.05) hemodynamic response to inhaled NO included a transient decrease in systolic (-10%), diastolic (-8%), and mean (-10%) pulmonary artery pressures; a decrease in pulmonary vascular resistance (-22%); an increase in mixed venous hemoglobin O2 saturation (+6%); and a decrease in arteriovenous O2 content difference (-7%). During NO inhalation, there was no change in systemic arterial or pulmonary wedge pressures. Methemoglobin levels remained < 1%. Inhalation of this concentration of NO for 10 min causes transient pulmonary artery vasodilation and hemodynamic improvement in patients with mild chronic pulmonary artery hypertension after mitral valve replacement. PMID- 1443741 TI - A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia. AB - A number of recent studies have suggested that the analgesic effects of highly lipid-soluble opioids are similar when these agents are administered either epidurally or intravenously. We sought to test whether the lipid-soluble opioid sufentanil was more effective when administered intrathecally than when administered epidurally or intravenously. Twenty-four women during active labor received sufentanil 10 micrograms either intrathecally (n = 9), epidurally (n = 8), or intravenously (n = 7), using a combined spinal-epidural technique. The sufentanil was administered alone, without concomitant local anesthetics. Analgesia was assessed using the visual analogue score as well as the time elapsed from the administration of study drug to the patient's request for additional analgesia via the epidural catheter (bupivacaine 0.25%). The median duration of analgesia (median, interquartile range) was 84 (70-92) min in the intrathecal group, 30 (23-32) min in the epidural group, and 34 (17-30) min in the intravenous group (P < 0.001). The intrathecal group showed rapid and significant decrease in visual analogue scale scores, whereas visual analogue scale scores in the other two groups did not decrease and remained significantly elevated compared to those of the intrathecal group at all observation points. Side effects were limited to pruritus in 3 patients (2 moderate and 1 severe) in the intrathecal group. No patient developed post-dural puncture headache. We conclude that sufentanil 10 micrograms intrathecally provides rapid and effective analgesia of 1-2-h duration during labor. Epidural and intravenous use of this dose of sufentanil did not provide evidence of satisfactory analgesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443742 TI - Effects of isoflurane and nitrous oxide in subanesthetic concentrations on memory and responsiveness in volunteers. AB - Awareness, defined as conscious memory during anesthesia, has been a problem in anesthesia practice. To determine the effect of isoflurane and nitrous oxide (N2O) on memory, 17 healthy adult volunteers were randomly assigned to receive isoflurane or N2O and received the alternate agent 1-2 weeks later. Each volunteer was studied at four end-tidal concentrations of each agent, consecutively 0.15, 0.3, 0.45, and 0.15 times the minimum alveolar concentration (MAC) for isoflurane or 0.3, 0.45, 0.6, and 0.3 times MAC for N2O. After 15-min equilibration at each end-tidal concentration, volunteers were tested for voluntary response to command and were presented with verbal information to be recalled after anesthesia. Volunteers were interviewed on the day after the study and tested for conscious and unconscious memory of the information presented during anesthetic administration. MAC-awake (the end-tidal concentration preventing voluntary response in 50% of volunteers) was 0.38 (0.35-0.42) times MAC for isoflurane and 0.64 (0.61-0.68) MAC for N2O (means, 95% confidence limits), indicating isoflurane to be more potent than N2O in suppressing voluntary response (P = .0001). Memory data were analyzed in 12 volunteers who completed the study and in whom the allocation of information to be recalled was counterbalanced among agents and concentrations of agents. Memory was decreased by increasing concentrations of both agents. Conscious memory of the information presented during anesthetic administration was prevented by 0.45 MAC isoflurane but not completely prevented by 0.6 MAC N2O. Unconscious memory (defined as memory of information without conscious recognition) occurred during administration of both agents and was prevented by 0.45 MAC isoflurane but not by 0.6 MAC N2O. Isoflurane was more potent in suppressing memory than MAC-equivalent concentrations of N2O. Using models of the relationship between dose of agent and suppression of memory, a dose of both agents was estimated that suppressed memory by 50% (ED50). The ED50 was 0.20 MAC for isoflurane (95% confidence intervals, 0.15-0.25), and 0.50 MAC for N2O (95% confidence intervals 0.43-0.55). We conclude that isoflurane and N2O suppress memory in a dose-dependent manner, and that isoflurane is more potent in preventing memory and voluntary response to command than MAC-equivalent concentrations of N2O. PMID- 1443743 TI - Pharmacokinetics of rocuronium bromide (ORG 9426) in patients with normal renal function or patients undergoing cadaver renal transplantation. AB - To determine the effect of end-stage renal disease on the pharmacokinetics of reocuronium bromide (ORG 9426), a new nondepolarizing monoquaternary steroidal neuromuscular blocking drug, the authors administered 600 micrograms/kg rocuronium (2 x ED95) intravenously to ten patients undergoing cadaver renal transplantation and ten healthy patients undergoing elective minor surgery (controls). All patients were anesthetized with nitrous oxide (50-70% in oxygen) and isoflurane (end-tidal concentrations of 1.2 +/- 0.5% and 0.8 +/- 0.2%, mean +/- SD, for control and transplant groups, respectively). Plasma concentrations of rocuronium were determined by capillary gas chromatography. A population-based pharmacokinetic analysis (NONMEM) was used to determine typical values, standard errors, and interindividual variability for the pharmacokinetic parameters and to determine whether these values differed between control and renal transplant patients. Total plasma clearance (2.89 +/- 0.25 ml.kg-1.min-1, mean +/- SE) and volume of the central compartment (76.9 +/- 10.6 ml/kg) did not differ between control and renal transplant patients, whereas volume of distribution at steady state was greater in renal transplant patients (264 +/- 19 ml/kg) than in control patients (207 +/- 14 ml/kg). This resulted in a longer elimination half life in renal transplant patients (97.2 +/- 17.3 min) compared to controls (70.9 +/- 4.7 min). The authors conclude that renal failure and renal transplantation alter the distribution but not the clearance of rocuronium. PMID- 1443744 TI - Prevalence of latex sensitization among hospital physicians occupationally exposed to latex gloves. AB - Patients undergoing surgery who have a history of occupational exposure to latex gloves may be predisposed to intraoperative anaphylaxis caused by latex allergy. Thus, medical personnel who routinely wear latex gloves may be at higher risk than the general population. The prevalence of latex sensitization has not been reported previously among physicians using latex gloves in a North American hospital setting. Using a latex skin prick test (SPT), we determined the prevalence of latex sensitization among 101 staff anesthesiologists, radiologists, and surgeons who regularly use latex gloves and among 100 atopic controls who were not occupationally exposed to latex gloves. Latex SPT was positive in 10 of 101 physicians (rho = 0.099; 95% confidence interval [CI] 0.041, 0.157) and 3 of 100 controls. Subgroup analysis showed that 9 of 38 atopic physicians were SPT-positive (rho = 0.237; 95% CI 0.102, 0.372). Atopic physicians were more likely to be latex SPT-positive than either nonatopic physicians or atopic controls (atopic vs. nonatopic physicians: P = 0.0006, odds ratio = 19.2, 95% CI 15.4, 23.1; atopic physicians vs. atopic controls: P = 0.0005, odds ratio = 9.1, 95% CI 7.5, 11.6). We conclude that compared to nonatopic physicians exposed to latex, or nonexposed atopic controls, atopic physicians who wear latex gloves are at increased risk of latex allergy. PMID- 1443745 TI - Respiratory interaction after spinal anesthesia and sedation with midazolam. AB - The combined use of midazolam and spinal anesthesia is common in clinical practice. Despite the known potential for each to alter ventilation, the effect of their interaction has not been examined. Nineteen healthy volunteers were studied to assess the impact of intravenous midazolam (0.05 or 0.075 mg/kg), spinal anesthesia (T3-T8; mean level, T6), and their combination on resting ventilation and ventilatory responses to progressive hyperoxic hypercapnia. Resting ventilatory pattern was altered significantly by each condition. Midazolam caused a 29% decrease in resting tidal volume and a 24% decrease in mean inspiratory flow rate, while respiratory frequency increased by 14% and minute ventilation remained unchanged. By contrast, spinal anesthesia alone caused a 32% increase in tidal volume, a 24% increase in mean inspiratory flow rate, and a 13% increase in minute ventilation accompanied by a 14% decrease in respiratory frequency. The combination of midazolam and spinal anesthesia caused a significant decrease in minute ventilation (19%), tidal volume (28%), and mean inspiratory flow rate (27%), all of which were significantly more than the predicted sum of the individual interventions. Midazolam and spinal anesthesia each produced a significant decrease in hypercapnic ventilatory response slope, whereas their combination provoked no net change in hypercapnic ventilatory response slope. Interpretation of the hypercapnic ventilatory response data was complicated by shifts in the position of the ventilatory response curve, particularly under the spinal anesthesia condition. It is concluded that intravenous midazolam depresses resting ventilation, spinal anesthesia stimulates resting ventilation, and their combination has a modest synergistic effect of depressing resting ventilation. PMID- 1443746 TI - The antiemetic effect of lorazepam after outpatient strabismus surgery in children. AB - The high incidence of postoperative emesis after strabismus surgery in pediatric outpatients can be reduced by the prophylactic administration of droperidol 75 micrograms/kg intravenously. However, this may be associated with profound sedation, delayed discharge, dysphoria, agitation, and extrapyramidal symptoms in this population. Because lorazepam used as an antiemetic in children during chemotherapy decreased the incidence of nausea and vomiting, we compared the antiemetic effects of lorazepam and droperidol in a randomized, double-blind, placebo-controlled study of 129 healthy children undergoing surgical correction of strabismus. The children, aged 1-13 yr, were randomly allocated into three groups. The children in group 1 received droperidol 75 micrograms/kg intravenously; those in group 2 received lorazepam 10 micrograms/kg intravenously; and those in group 3 received placebo. Anesthesia consisted of halothane, nitrous oxide in oxygen, and atracurium. Study drugs were administered intravenously after induction of anesthesia but before surgery. In children 3-13 yr old, administration of either lorazepam or droperidol was associated with a lower (P < 0.024) incidence of postoperative vomiting. There was no difference between the antiemetic effect of lorazepam and that of droperidol. The incidence of postoperative agitation was greater in the droperidol group (P < 0.001) than in the lorazepam and placebo groups. Postdischarge vomiting was less (P < 0.009) in children younger than 3 yr of age. Lorazepam, similar to droperidol, has an antiemetic effect in outpatient children 3-13 yr old undergoing strabismus correction, but it is associated with less postoperative agitation than is droperidol. PMID- 1443747 TI - No correlation between quantitative electroencephalographic measurements and movement response to noxious stimuli during isoflurane anesthesia in rats. AB - A meaningful use of the electroencephalogram (EEG) for monitoring depth of anesthesia has proven elusive. Although changes in the EEG with changing anesthetic dose or concentration have been noted for 60 yr, it has been difficult to demonstrate reliable, quantitative correlation between the EEG and other physiologic measures of anesthetic depth. We attempted to correlate several quantitative EEG measurements in rats, including average amplitude, spectral edge frequency, and burst suppression ratio, with the movement response to supramaximal noxious stimulation. We anesthetized 21 Sprague-Dawley rats with isoflurane 1.5% and allowed them to breathe spontaneously. After equilibration, EEG was recorded for off-line analysis; then a noxious stimulation was delivered with a tail clamp and the somatic response noted. Isoflurane concentration was adjusted up and down, and the EEG and movement response to tail clamp were assessed at each level until the minimum alveolar concentration was determined in each rat. We found no EEG dose response to increasing inspired concentrations of isoflurane, except for an increasing degree of burst suppression. We found no difference in any parameter between rats that responded and those that did not respond to stimuli at a given concentration of isoflurane. Finally, we found that the presence of burst suppression did not predict lack of response. PMID- 1443748 TI - The general anesthetic potency of propofol and its dependence on hydrostatic pressure. AB - Although plasma concentrations of propofol during anesthesia are well known, the free concentration remains unknown because of uncertainties regarding plasma protein binding, interaction with other protein-bound substances, the level of binding to its lipid carrier, and the use of adjuvants. At elevated surrounding pressure, all general anesthetics require higher concentrations to reach adequate levels of anesthesia. To determine the anesthetic potency of propofol at equilibrium conditions and to study the effects of pressure on propofol-induced anesthesia, Rana pipiens tadpoles were exposed to different concentrations of pure, not emulsified, propofol in aqueous solution. Anesthesia was defined as loss of the righting reflex. Ten animals per concentration were used, and each experiment was conducted twice. Pressure experiments were performed with nonanesthetized tadpoles and urethane-anesthetized tadpoles as control groups. Propofol concentrations were measured spectrophotometrically. At 1 atmosphere absolute (atm abs), a semilogarithmic sigmoidal concentration-response curve was obtained with a half-maximal effect of propofol at 2.2 +/- 0.22 microM (EC50; mean +/- SE). Increased pressure shifted the concentration-response curve to the right. The EC50 increased linearly with increasing pressure up to 121 atm abs (EC50 at 121 atm abs = 4.1 +/- 0.41 microM). For pressure greater than 121 atm abs, an increased excitability of the tadpoles made it difficult to distinguish the righting reflex from involuntary movements. The saturated solubility of propofol in aqueous solution was found to be 1.0 +/- 0.02 mM (mean +/- SD), and the octanol/water partition coefficient was 4,300 +/- 280. Propofol adhered to the correlation between anesthetic potency and octanol/water partition coefficient exhibited by other general anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443749 TI - Local anesthetic-induced conduction block and nerve fiber injury in streptozotocin-diabetic rats. AB - Patients with diabetes may have peripheral neuropathy, which may have clinical implications for the use of regional nerve block. The effects of local anesthetics on nerve conduction and nerve fiber injury were tested in control rats and at 4 weeks after the onset of diabetes in rats injected with streptozotocin (50 mg/kg intraperitoneally). Nerve conduction was assessed by recording evoked electrical activity in hindpaw muscles following ipsilateral electrical stimulation of the sciatic nerve near the hip. Block of motor nerve conduction was quantified by recording the amplitude of the evoked response at 1 min intervals for up to 15 min after the injection of 500 microliters 1% lidocaine HCl or procaine HCl into the midthigh next to the sciatic nerve. In control animals, procaine was much less effective than lidocaine in producing conduction block. The rate and magnitude of lidocaine-induced conduction block were not significantly different between control and diabetic groups. However, conduction block due to procaine was sufficiently enhanced in diabetic rats to become comparable to that of lidocaine-treated control nerves. Long-lasting injury was assessed in sciatic nerve harvested 2 days after the extraneural injection of saline or 2 or 4% lidocaine HCl. Using a light microscope with a superimposed grid, nerve edema was quantified as the proportion of intersection points falling on extracellular space. Lidocaine induced edema in both control and diabetic nerves, but 4% lidocaine induced significantly more edema in diabetic nerves than in controls. Nerve fiber injury, based on light microscopic scoring of axonal degeneration and demyelination, was not observed in saline treated nerves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443750 TI - Effects of propofol and thiopental in isolated rat aorta and pulmonary artery. AB - This study was performed to determine if direct arterial dilating actions of propofol contribute to the drug's hypotensive actions. The effects of propofol were compared with those of thiopental on isolated vascular ring preparations from rat thoracic aorta and pulmonary artery. Thoracic aortic ring responses were evaluated in the presence and absence of endothelium, indomethacin, and N omega nitro-L-arginine methyl ester (LNAME; a specific inhibitor of endothelium-derived relaxing factor-nitric oxide [EDRF/NO] synthase). Pulmonary artery responses were investigated with intact endothelium. After the induction of active isometric force by a predetermined EC50 dose of phenylephrine for each ring, effects of propofol (30, 100, 300 microM) and thiopental (10, 30, 100 microM) were examined. Propofol caused significant vasodilation in endothelium-intact, endothelium denuded, and LNAME-treated aortic rings. In the endothelium-intact aortic and pulmonary artery rings, the initial vasodilation due to 30 and 100 microM propofol showed gradual and partial recovery over 15 min; 300 microM propofol caused sustained vasodilation. Endothelium-denuded rings and LNAME-pretreated endothelium-intact rings showed constant and sustained vasodilation with all propofol concentrations. Propofol also caused marked vasodilation in pulmonary arteries. In contrast, thiopental had no vasodilating effect in aortic or pulmonary artery preparations. In control experiments, propofol vehicle (Intralipid) also had no effect on vascular rings. Indomethacin pretreatment induced a dose-dependent vasoconstriction by thiopental in endothelium-intact rings and decreased the vasodilation due to propofol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443751 TI - Direct effects of propofol on myocardial contractility in in situ canine hearts. AB - The pronounced decrease in arterial blood pressure evident during anesthetic induction with propofol has raised the possibility that propofol has a direct negative inotropic effect. Previous attempts to evaluate this mechanism in vivo have been inconclusive because of confounding variables associated with intravenous administration of propofol. Accordingly, in the current study, steady state changes in myocardial contractility and related hemodynamic parameters were assessed during intracoronary infusions of propofol in seven open-chest dogs anesthetized with fentanyl and midazolam. The left anterior descending coronary artery (LAD) was cannulated and perfused at controlled pressure (100 mmHg) with normal arterial blood. In LAD-perfused myocardium, contractility was evaluated from measurements of percent segmental shortening (%SS) obtained with ultrasonic crystals. Coronary blood flow in LAD was measured electromagnetically and used to calculate myocardial oxygen consumption (MVO2; Fick principle) and coronary propofol concentration. Propofol was infused into the LAD at 150, 300, 600, and 1,200 micrograms/min (P-150, P-300, P-600, P-1,200). These infusion rates yielded calculated blood concentrations of 7 +/- 1, 15 +/- 1, 26 +/- 2, and 50 +/- 5 micrograms.ml-1, respectively. The calculated blood concentrations at P-150 were in the clinical range, whereas those at P-300, P-600, and P-1,200 were supratherapeutic. P-150 had no effect on %SS, whereas higher infusion rates caused decreases in %SS. Changes in MVO2 by propofol generally paralleled changes in %SS. At P-150 and P-300, coronary blood flow was proportional to MVO2, whereas at P-600 and P-1,200, coronary blood flow was in excess of the prevailing MVO2, resulting in increased coronary venous oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443752 TI - Sleep disruption and increased apneas after pontine microinjection of morphine. AB - The medial pontine reticular formation (mPRF) is a cholinoceptive brain stem region known to play a key role in regulating rapid eye movement (REM) sleep and state-dependent ventilatory depression. Numerous lines of evidence have shown that opioids inhibit both cholinergic neurotransmission and REM sleep. The present study examined the hypothesis that morphine applied to the cholinoceptive mPRF would inhibit REM sleep and alter ventilation. In six cats, guide cannulas were chronically implanted to permit pontine microinjection of morphine sulfate, naloxone, and the cholinergic agonist carbachol. After each mPRF microinjection, 2-h polygraphic recordings quantified respiratory frequency and the percent of time spent in states of wakefulness, non-REM sleep, and REM sleep. The results show that mPRF administration of morphine significantly inhibited REM sleep and that this REM sleep inhibitory effect was blocked by pretreating the mPRF with naloxone. Apneic episodes were increased after injection of morphine alone, and the apneas were decreased by the cholinergic agonist carbachol. The results also demonstrated that the ability of microinjected morphine to inhibit REM sleep was dose-dependent and site-dependent. Considered together, the site-localization, pharmacologic blocking, and dose-response data support the hypothesis that specific regions of the mPRF can contribute to the long-recognized ability of morphine to inhibit REM sleep and alter respiratory control. PMID- 1443753 TI - Histologic examination of the rat central nervous system after intrathecal administration of human beta-endorphin. AB - The objective of this study was to evaluate histologically the toxicity of human beta-endorphin on the rat central nervous system after intrathecal administration. Animals received a single injection of 5 micrograms (n = 9) or 50 micrograms (n = 10) on each of four consecutive days, while others received 50 micrograms (n = 8) as a single dose. The control groups received either physiologic saline (n = 10) during each of four consecutive days or had sham operations (n = 4). Tests for nociception (tail-flick latency), motor function, and reflexes (righting reflex, eye-blink reflex, and inclined plane) were performed 5, 15, 30, 60, and 120 min after injection. Both dosages produced a dose-dependent impact on these parameters. In the 50-micrograms group, there were no significant differences in analgesia between the first and the fourth doses injected. The 50-micrograms dose produced catalepsy in some animals. All changes returned to baseline within 24 h. One animal in the 50-micrograms group developed hind limb paralysis after a single injection. Histologic sections from brain, brain stem, and spinal cord were prepared. No changes in histology were found except for that in the paretic animal, which had anoxic changes in the hippocampus and other cortical areas. Human beta-endorphin produced no neurotoxicity. The effect on nociception, reflexes, and motor function confirmed the results of previous studies. PMID- 1443754 TI - Impact on knowledge and practice of a multiregional long-term care facility infection control training program. AB - BACKGROUND: Few affordable training opportunities are specifically designed for the long-term care facility infection control practitioner. There is also little evidence of the success of training in improving infection control practices. The Nebraska Infection Control Network developed a 2-day basic skills training program for Midwestern long-term care facility infection control practitioners that was later disseminated to eastern and western training sites. In this study we examined the effectiveness of the training program in terms of trainee knowledge and practice. METHODS: From 1986 to 1990, a total of 17 courses conducted at the three sites were attended by a total of 266 infection control practitioners. Trainees completed a 40-item multiple choice test before and after training to evaluate their knowledge gain. Implementation of eight key infection control practices and time devoted to infection control duties were measured before training and at 3 and 12 months after training. Implementation of infection control practices was also evaluated in a second study, with infection control practitioners randomly assigned to trained and wait-control conditions. RESULTS: Significant increases after training were found at each site for both knowledge and implementation measures. These increases were maintained at 12 months follow-up. Time devoted to infection control duties increased significantly at the midwest and western sites but not at the eastern site. In the second study, significant differences were found between the trained and the wait-control group in use of infection control practices, providing evidence for a causal relationship between training and increased use of practices. CONCLUSIONS: The training program was effective in producing improvements in knowledge and implementation of recommended infection control practices in long term care facilities. These improvements were consistent across three diverse geographic areas. There were some specific geographic differences. PMID- 1443755 TI - A retrospective study of nosocomial pneumonia at a long-term care facility. AB - BACKGROUND: Results of a passive surveillance system (pneumonia confirmed by x ray examination) suggested that in 1989 a total of 187 cases of nosocomial pneumonia had occurred at the Canandaigua Veterans Administration Medical Center among 250 long-term care patients. METHODS: A retrospective study was undertaken to validate cases and to enumerate risk factors. A chart review showed that 136 of 187 cases (72%) met predetermined criteria for nosocomial pneumonia. RESULTS: Three nursing units characterized as at high risk had a pneumonia rate of 1.90 per 1000 patient days, as compared with a rate of 0.70 cases per 1000 patient days on the two other units. There were no differences in age, mean white blood cell count, or clinical symptoms between high- and average-risk patients. Two thirds of all patients had a history of chronic aspiration. High-risk patients were more likely to be confined to bed, to have a debilitating neurologic disease, and to require tube feedings. Twenty percent of patients on high-risk units died of nosocomial pneumonia or with nosocomial pneumonia as a contributory factor. CONCLUSIONS: Facility-associated pneumonia is an important cause of morbidity and mortality in long-term care facilities. PMID- 1443756 TI - Bacteremia in transplant recipients: a prospective study of demographics, etiologic agents, risk factors, and outcomes. AB - BACKGROUND: Bacteremic infections are a major cause of death among organ transplant recipients. We sought to identify the risk factors associated with death and examine the timing of the bacteremic episode after operation to recognize patients who may benefit from perioperative prophylactic antibiotic therapy. METHODS: A total of 125 episodes of bacteremia or fungemia in 16 heart, 26 kidney, and 70 liver recipients were monitored prospectively in 1 year. RESULTS: The urinary tract was the most frequent portal for kidney recipients, the gastrointestinal and biliary tracts were frequent for liver recipients, and the lung was frequent in heart recipients. Heart and liver recipients were more severely ill at the time of bacteremia and had bacteremia sooner after operation. Death at 14 days after onset of bacteremia was 33% in heart recipients, 24% in liver recipients, and 11% in kidney recipients. Risk of death was associated with the severity of the underlying condition of the transplant recipient, the source of the bacteremia, and the microbial agent. Pseudomonas aeruginosa and Enterobacter species had fatality rates of 47% and 63%, respectively. P. aeruginosa and Enterobacter were also most commonly associated with failures of perioperative antibiotic prophylaxis. CONCLUSIONS: There are distinct clinical patterns of bacteremia in transplant recipients. The emergence of P. aeruginosa and Enterobacter species in the immediate postoperative period appeared to be a significant cause of morbidity and death among transplant recipients. PMID- 1443757 TI - Emergence and control of methicillin-resistant Staphylococcus aureus in a children's hospital and pediatric long-term care facility. AB - BACKGROUND: After a 6-year quiescence, methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 30 patients in a children's hospital and a pediatric long-term care facility from November 1987 through April 1989. After six nosocomial cases had occurred at the children's hospital, increased infection control measures directed at MRSA were initiated in August 1988. Because MRSA had been identified in three patients in the pediatric long-term care facility within 24 hours of their admission to the children's hospital, other patients transferred from the pediatric long-term care facility to the children's hospital were isolated and screened for MRSA. METHODS: We reviewed the medical records of these patients and evaluated their response to therapy with rifampin alone or in combination with trimethoprim-sulfamethoxazole. RESULTS: In the 8-month period after initiation of infection control measures, MRSA was identified in 10 residents of the pediatric long-term care facility; there was also one nosocomial children's hospital case. Phage typing showed that one MRSA strain predominated in patients at the pediatric long-term care facility but did not implicate this strain as the source for MRSA introduction into the children's hospital. Of 16 patients with MRSA who completed therapy and were available for follow-up, 13 (81%) had elimination of colonization. CONCLUSION: Prompt institution of MRSA surveillance, barrier isolation, and therapy to eliminate colonization should be considered in hospitals with a new introduction of MRSA. PMID- 1443758 TI - The problem of transfusion-associated acquired immunodeficiency syndrome in Africa: a quantitative approach. AB - BACKGROUND: Transfusion-associated AIDS accounts for 10% of all cases of AIDS in Africa. The risk of HIV-1 contamination in transfusions continues to exist, even in countries where blood products are screened, because of limitations in test sensitivity, human error, and the window period. Furthermore, 30 African countries do not screen all of their blood products because of resource limitations. METHODS: This study used decision analysis to compare the survival outcomes of severely anemic patients who are transfused with those of patients who are not transfused. Sensitivity analyses were performed. RESULTS: When 5% of the blood supply is HIV-1 contaminated, every patient with a 6.6% or greater risk of dying from anemia should be transfused. Detailed results are provided for a wide range of HIV-1 contamination rates. CONCLUSIONS: This study provides a method for developing and evaluating locality-specific transfusion guidelines. This method can be applied to other regions, including the United States, and to other diseases transmitted by blood products. PMID- 1443759 TI - Design and dissemination of a multiregional long-term care infection control training program. AB - Long-term care facilities have only recently begun to receive attention in the area of infection control. A training program was developed in Nebraska to help supply practitioners with knowledge and techniques designed specifically for the long-term care environment. This program's success led to its implementation in other regions. The regional extensions of the program were designed to operate with independent faculty but standardized course materials. PMID- 1443760 TI - Determinants of failure in superficial femoral artery angioplasty. AB - Although results of iliac artery balloon angioplasty have been shown to be good, there are much less data regarding initial success and durability of superficial femoral artery (SFA) dilation. The authors retrospectively reviewed the results of 22 patients treated for 27 SFA lesions between 1981 and 1986. Mean age was 64.5 years (fifty-five to seventy-six). Results were analyzed with respect to initial, early (< twelve months), and late (> twelve months) angiographic and clinical success. Indications were claudication (22), nonhealing ulcer (3), and rest pain (2). Mean follow-up was 30.9 months; 100% at one year and 92% at two years. Initial failure occurred in 9 (33%) lesions. There were 2 early and 2 late failures for a cumulative patency rate of 90.3% and 78% at one and two years, respectively. Predictors of clinical failure were: (1) initial--age, SFA occlusion, and angioplasty rating; (2) early--age, SFA occlusion, degree of atherosclerosis, and angioplasty rating; (3) late--angioplasty rating. There were 3 complications (11%). The authors conclude that: (1) 33% of attempted SFA angioplasties were initially unsuccessful and that the cumulative patency rate was 78% at two years. (2) Age is predictive of initial and early failure; SFA occlusion, of initial and early failure; degree of atherosclerosis, of early failure; and angioplasty appearance, of initial, early, and late failures. (3) Complications did not result in limb loss or require surgery. PMID- 1443761 TI - Immediate anticoagulation for intracardiac thrombus in acute cardioembolic stroke. AB - To assess the efficacy of immediate anticoagulation therapy on intracardiac thrombus formation in acute cardioembolic stroke, serial two-dimensional echocardiographic examinations were performed in 25 patients with acute cardioembolic stroke. Anticoagulation therapy was commenced within two days of onset in 7 patients (group A) but not in 18 patients (group B). Appearance or enlargement of intracardiac thrombi were not detected in group A but were noted in 7 patients (39%) of group B. Recurrence of systemic embolism was demonstrated in 3 patients (17%) of group B. There were no serious hemorrhagic complications in either group. Immediate anticoagulation could, therefore, be effective in preventing intracardiac thrombus formation and the consequent recurrence of systemic embolization in acute cardioembolic stroke. Because the study was preliminary and not randomized, further randomized study is desirable to establish the efficacy of immediate anticoagulation therapy. PMID- 1443762 TI - Procion yellow fluorescent microscopy: a new method of studying arterial and venous pathology. AB - A new means of studying vessel wall pathology is presented. This technique utilizes Procion yellow, a vital fluorescent dye, to stain and delineate the connective elements, matrix, and elastic tissue within the arterial wall. In addition, penetration of the dye into cells provides evidence of membrane pathology. A canine model was used, and clamped segments of femoral artery were stained and examined. The appreciation of this approach for the examination of the vessel wall shows alterations in tissue elements that have not been reported previously. This technique makes possible a unique means of studying connective tissue elements as well as membrane integrity. PMID- 1443764 TI - Vascular effects of noise. AB - The possible vascular effects of noise were studied. A study of the carotid vessels was made with Doppler ultrasonography in two groups of subjects exposed to various intensity of noise. The following data were studied: age, blood pressure, serum cholesterol, blood glucose, smoking habits, excess weight, electrocardiographic anomalies, family history of vascular disease, connection with duration of exposure and the type of noise and with audiometric deficits, and cerebrovascular modifications after postural changes and after a stress test. The control group comprised subjects not exposed to noise. The findings confirm that noise does play a role in causing vascular modifications that can be detected early by use of Doppler ultrasonography. This technique is predictive and could be useful in screening campaigns, following the method suggested here. PMID- 1443763 TI - Microcirculation in systemic hypertension. AB - In 40 patients with idiopathic systemic hypertension, skin blood flow was evaluated with laser-Doppler flowmetry, transcutaneous measurements of partial pressure of oxygen (PO2) and partial pressure of carbon dioxide (PCO2), and determination of capillary permeability before and after treatment with nifedipine (10 mg tid for four weeks). Also 35 normal subjects matched for age and sex distribution were studied. Before treatment, microcirculatory studies showed a significant decrease in skin flow and venoarteriolar response in hypertensive patients in comparison with normal subjects. Moreover, PO2, PCO2, and capillary permeability were significantly lower in hypertensives. All these microcirculatory parameters significantly increased after nifedipine treatment while both systolic and diastolic pressures decreased. In conclusion, laser Doppler flowmetry used with other microcirculatory techniques was able to discriminate between normal subjects and hypertensive patients, and it was able to show the improvement in the microcirculation after nifedipine treatment. PMID- 1443765 TI - Assessment of valvular regurgitation using cine magnetic resonance imaging coupled with phase compensation technique: comparison with Doppler color flow mapping. AB - To elucidate whether or not a newly developed technique in cinematic-displayed (cine) magnetic resonance imaging (MRI) can improve the semiquantitative evaluation of valvular regurgitant flow, 20 patients with valvular lesions were studied. Three pulse sequences of cine MRI, ie, standard, short echo time (TE), and rephasing scans, were compared with reference obtained by Doppler color flow mapping. Short TE technique and rephasing scan technique improved image quality remarkably as compared with standard technique. Each of the three cine MRI techniques showed good correlation with the Doppler method (p < 0.001). However, short TE and rephasing scan techniques gave a faithful estimation of the extent as compared with the Doppler method, whereas standard technique overestimated the regurgitation. Thus, cine magnetic resonance imaging with phase compensation technique can be utilized for the semiquantitative assessment of valvular regurgitation in a manner similar to that of Doppler color flow mapping. PMID- 1443766 TI - Lymphoscintigraphy of head-and-neck cancer. AB - To achieve the visualization of regional lymph nodes by lymphoscintigraphy, 21 patients with head-and-neck cancer were studied with the aid of 99mTc-labeled rhenium sulfur colloid (99mTc Re). Four injection sites were selected; the injections were given into the subcutaneous tissue of the parietal area of 11 patients, into the submucosa of the retromolar area of 6 patients, into the subcutaneous tissue of the postauricular area of 2 patients, and into the thyroid glands of 2 patients. Lymphoscintigraphy was done three hours after the injection. The cervical regions were visible in 85.7% of the patients on the affected side and in 90.5% on the healthy side. The visualization comprised the following regions: submental, submandibular, deep cervical, accessory, and supraclavicular regions. In total, 102 nodes were visualized on the affected side (average 4.8 per patient) and 110 nodes in the healthy side (average 5.5). Histologically, 15 of 21 patients had lymph nodes metastases and 6 did not. Of these 21 patients, 66.7% (14/21) had confirmed lymph node metastases in the visualized regions. This technique appears to be a relatively easy and efficient method of imaging the regional lymph nodes in head-and-neck cancer both before treatment and after neck surgery. PMID- 1443767 TI - Role of the captopril test in renovascular hypertension: a case report. AB - This article reports the case of a rapidly severe stenosis of the right renal artery, causing uncontrolled hypertension. After failure of a percutaneous transluminal renal angioplasty, which provoked the thrombosis of the vessel, a surgical revascularization was performed after +/- eighteen hours of renal ischemia. Blood pressure, blood urea nitrogen and serum creatinine returned to normal values. A dramatic improvement of the right renal function was attested at the hippuran scintigraphy after a dose test of captopril. The results of renographic studies obtained in this clinical case underline the role of the captopril radionuclide test in detection and follow-up after treatment of renovascular hypertension. PMID- 1443768 TI - A case of ventricular tachycardia refractory to medical treatment related to a cystic mass in left ventricle--a case report. AB - This is a case report of a twenty-two-year-old woman who had attacks of ventricular tachycardia that could be prevented by the use of various antiarrhythmic drugs for three months. Electrophysiologic study showed that the mechanism of the tachycardia was "reentry." In cardiac catheterization a non contractile mass having calcification was seen on the apical portion of the left ventricle. Angiographically, the mass resembled a diverticulum. Recurrence of attacks was terminated by resection of this mass, which had a cystic appearance. PMID- 1443769 TI - Pulmonary artery catheterization: the right heart should not be left out--a case report. AB - Tricuspid valve stenosis in the setting of endocarditis is associated with a high morbidity. Diagnostic approaches incorporate a high clinical index of suspicion, echocardiographic evidence, and inferences about hemodynamic data derived from pulmonary artery catheterization. As demonstrated by the case presented herein, inadequate initial evaluation of right-sided pressures delayed the diagnosis and treatment of prosthetic tricuspid valve stenosis. PMID- 1443770 TI - Local thrombolysis and percutaneous transluminal venoplasty for the venous complications of thoracic outlet syndrome: case report. PMID- 1443771 TI - Biochemical evidence of the expression of two major histocompatibility complex class I genes on bovine peripheral blood mononuclear cells. AB - For a long time, the bovine major histocompatibility complex (MHC) (BoLA) class I region was characterized, rather uniquely among mammalian species, as having one expressed locus. Recent reports have suggested otherwise. Selective immunoprecipitation and molecular characterization of products enable a decisive answer to the question of whether there is indeed more than one locus expressed. Therefore, we characterized serologically defined w10 encoding haplotypes in European and African cattle by immunoprecipitation of [35S]-methionine-labelled peripheral blood mononuclear cells (PBMC), followed by one- and two-dimensional isoelectric focusing (1D/2D-IEF) of cell lysates. Monoclonal antibodies (mAb) used were directed against either human class I monomorphic determinants (W6/32 and B1.1G6) or bovine polymorphic determinants expressed on products encoded by serologically defined w10 encoding haplotypes of Boran and Friesian cattle. Sequential immunoprecipitations with W6/32 and B1.1G6 using lysates of PBMC of British Friesian cattle, revealed that from this haplotype W6/32 precipitated one product, whereas B1.1G6 precipitated two products. The product precipitated in addition appeared to be the one that was selectively precipitated by the mAb directed against polymorphic determinants on a product of w10 encoding haplotypes. Additionally, peptide maps of protease V8-digested precipitates showed that this particular 'w10' associated product was distinctly different from the product recognized by W6/32. Thus, we suggest that the two products are distinct gene products and that the product with higher pI is associated with the serologically defined A-locus product, whereas the product with lower pI is the putative second locus product. In the African Boran breed, variants of the serologically defined w10 specificity were found on the basis of IEF typing. These variants appeared to be associated with different second locus products. Therefore, we conclude that serologically defined w10 encoding haplotypes encode at least two independent class I locus products, expressed on normal bovine PBMC. In IEF analysis the additional use of mAb recognizing polymorphic determinants on serologically defined A-locus products highly facilitated the detection and typing of second locus products. PMID- 1443772 TI - Cloning of highly polymorphic microsatellites in the horse. AB - We have isolated equine microsatellites by screening a genomic library with (TG)n and (TC)n probes. TG microsatellites were found to be more abundant than TC repeats, with an estimated frequency of one per 100,000bp. Sequence analysis of eight TG-positive clones revealed varying structures of the repeat regions; perfect stretches of TG repeats, imperfect stretches of TG repeats and compound regions of TG and TC repeats. Five loci were analysed by PCR and showed extensive polymorphism; three to seven alleles and heterozygosities of 0.40-0.76 were observed when screening 20-30 unrelated individuals. The high degree of polymorphism, their abundance and the possibility of automating the typing procedure make these loci ideal for standardized paternity testing in the horse. Furthermore, we demonstrate that single hairs can be used as starting material for the PCR analysis. PMID- 1443773 TI - Genetic polymorphism and close linkage of two plasma protein loci in dogs. AB - By using a simple method of two-dimensional horizontal electrophoresis, phenotypes of an unidentified plasma protein (PA4) were determined in 967 dogs belonging to 43 different breeds. Two codominant, autosomal alleles (F and S) of PA4 were reported. While many of the breeds of middle and north-eastern Asia (akita inu, Alaskan malamute, chow chow, samoyed, Siberian husky and Tibetan terrier) showed a substantial frequency (0.1 to 0.6) of the S allele, a majority of the European breeds had only the F allele. Evidence was provided that the PA4 locus is closely linked to the plasma pretransferrin 1 locus (PRT1). No recombinant was observed in 45 informative offspring studied. In nearly all breeds, the PA4 S allele was almost always in coupling phase with the PRT1 F allele. PMID- 1443774 TI - Genetic distances estimated from DNA fingerprints in crosses of white Plymouth Rock chickens. AB - Crosses were produced between two lines of White Plymouth Rock chickens, one of which had been selected for low 8-week body weight for 31 generations (L) and the other of which was a bantam population (B). The parental lines, reciprocal F1s, reciprocal F2s and all possible back-crosses to each parental line (total of 16 populations) were available for study. Blood was obtained from 10 females within each population. DNA was extracted from blood mixes (equal amounts of blood from each individual) for each population, and from blood samples of each individual in the two parental lines. Fourteen line-specific DNA fingerprint (DFP) bands (those bands present in one parental population, but not in the other parental population) were analysed (eight from line L and six from line B). Regression analyses were conducted to compare the known proportion of genomic contribution from each parental population with values based on relative band intensity obtained with a scanning densitometer. The resulting regression coefficient of 1.004 demonstrated that DFP analysis of relative band intensity is an effective method of estimating the relative proportion of genome contributed by parental populations. PMID- 1443775 TI - Rapid beta-lactoglobulin genotyping of cattle using the polymerase chain reaction. AB - A polymerase chain reaction (PCR) assay has been developed for genotyping beta lactoglobulin A and B variants in dairy cattle. Either blood or semen samples can be used as a source of DNA. The method is accurate, faster than Southern blot analyses and should prove a useful tool in breeding programmes. PMID- 1443776 TI - Detection of a three-allele single strand conformation polymorphism (SSCP) in the fourth intron of the bovine growth hormone gene. PMID- 1443777 TI - Ovine and bovine dinucleotide repeat polymorphism at the MAF46 locus. PMID- 1443778 TI - Ovine dinucleotide repeat polymorphism at the MAF209 locus. PMID- 1443779 TI - ILSTS002: a polymorphic bovine microsatellite. PMID- 1443780 TI - Ovine dinucleotide repeat polymorphism at the MAF70 locus. PMID- 1443781 TI - Ovine dinucleotide repeat polymorphism at the MAF33 locus. PMID- 1443782 TI - Ovine dinucleotide repeat polymorphism at the MAF50 locus. PMID- 1443783 TI - Alloreactive T-cell recognition of bovine major histocompatibility complex class II products defined by one-dimensional isoelectric focusing. AB - T-cell recognition of bovine MHC (BoLA) class II antigens was investigated in relation to BoLA class II polymorphisms defined by one-dimensional isoelectric focusing (1D-IEF). One-way mixed lymphocyte reactions (MLRs), and allospecific cell lines and clones were used. In general, T-cell responses correlated with the 1D-IEF defined haplotypes (EDF types). However, with MLRs some responses appeared to be associated with BoLA class I differences. All combinations of responder stimulator pairs produced alloreactive T-cell responses both in MLR and in generation of allolines/clones. Thus allospecific lines and clones were generated to all EDF types tested. Splits in the IEF typing were observed with EDF6 and EDF3, indicating that distinct BoLA class II haplotypes are not necessarily distinguished by 1D-IEF alone. Furthermore, the patterns of reactivity with EDF3 expressing cells were complex with the T-cell specificities splitting EDF3 into several distinct types. Also, in some cases it was clear that more than one T cell specificity per EDF type was detectable. Thus, allospecific lines and clones provide complementary and additional information to the 1D-IEF typing for polymorphism of the BoLA class II complex. This extra information is particularly important in terms of the functional significance of the BoLA complex for antigen presentation and immune response gene effects. PMID- 1443784 TI - [Sialic acid deficiency transferrin: a very promising biological marker, sensitive to chronic alcoholism]. AB - Chronical alcohol ingestion may induce conformational molecular modifications of plasma transferrin: alcohol modifies the content of its carbohydrates. The abnormal transferrin contains reduced amounts of carbohydrates, especially sialic acid, constituting its terminal trisaccharides biantennary chains. Plasma levels of partly deficient or asialotransferrin increase in chronically drinkers. In English speaking countries, it is called carbohydrate deficient transferrin or CDT. A positive correlation is obtained between the plasmatic concentration of CDT and the amount of ingested alcohol. Positivity and sensitivity of CDT are superior to those other usual biological parameters. The CDT quantitation may be proposed for the detection and the follow-up of alcohol drinkers, in order to evaluate the degree of intoxication, and during the period of withdrawal. PMID- 1443785 TI - [Variations of plasma Willebrand factor and fibrinogen in coronary pathology]. AB - In order to determine a marker of prethrombotic states, reliable and easy to measure, we studied 200 patients under 60 years of age admitted to hospital for a precordial chest pain. Four groups were established: transmural myocardial infarction, acute infarction without Q wave, unstable angina and atypical chest pain. Fibrinogen, von Willebrand factor, cholesterol, and triglyceride levels were measured as well as the white cell and platelet counts. There was a statistically significant correlation between transmural myocardial infarction and increased levels of fibrinogen, von Willebrand factor and white blood cells. Von Willebrand factor was already increased in the acute phase of transmural infarction, reached a maximum on the fifth day and then decreased slowly during the following ten days. This study suggests that plasma von Willebrand factor could be a reliable marker of transmural myocardial infarction in the acute phase or during the two weeks following the thrombotic event. PMID- 1443786 TI - [Assay of micronuclei in binucleated T-lymphocytes. Analysis of the distribution and variation factors in a population of 100 subjects]. AB - The authors analysed micronuclei levels distribution in lymphocytes of 100 non occupationally exposed subjects and studied the effect of age, sex and smoking of donors on the distribution. Results showed that micronucleated cells were distributed according to a normal distribution (average = 9.5 +/- 4 micronucleated cells in 1,000 binucleated lymphocytes). Age and sex of donors had no effect on the distribution but, concerning smoking, the results showed that micronuclei levels were correlated to the number of cigarettes daily smoked. PMID- 1443787 TI - [Comparison of different methods for serum folate assay]. AB - Folates were determined in 148 patient sera, using four different methods: a microbiological assay (Reference Method), two radioassays (Magic B12 FOL [NB] and SimulTRAC SNB no boil kits) and a non isotopic competition method (Magic Lite kit). Folate mean varied according to the methods 10.0 nmol.l-1 (reference method), 12.2 nmol.l-1 (Magic Lite), 8.7 nmol.l-1 (Magic B12 FOL [NB]) and 10.8 nmol.l-1 (SimulTRAC SNB NO boil). Poor correlations were also noted (0.83 < r < 0.95, figures 1 and 2). Differences between methods were explained according to the literature. PMID- 1443788 TI - [Evaluation of the immunoenzyme test (Elisa) in detecting Clostiridium difficile toxin A in fecal samples]. AB - Currently, the method of choice in diagnosis of Clostridium difficile-associated intestinal diseases is the detection of toxin B in fecal specimens. This method is long (72 h) and can be realized in laboratories which have tissue culture facilities. Commercial agglutination test have been evaluated but they lack in specificity. An immunoenzymatic test has been recently commercialized for detection of toxin A. We have compared the results of this assay on 275 fecal specimens from patients suspected of having Clostridium difficile-associated intestinal diseases with the results obtained with the cytotoxicity test and the culture. Of the 275 fecal specimens, 58 were positive in cytotoxicity and 53 in Elisa. The overall sensitivity and specificity of the Elisa compared with cytotoxicity were 89.5% and 99.0% respectively. The immunoenzymatic test detecting Clostridium difficile toxin A is an easy test to perform in 2 h 15; it displays a good correlation with detection of toxin B and can be very useful in daily laboratory diagnosis. PMID- 1443789 TI - International Federation of Clinical Chemistry, Scientific Division, Committee on Quantities and Units. Quantities and units for centrifugation in the clinical laboratory. PMID- 1443790 TI - International Federation of Clinical Chemistry, Scientific Division, Committee on Quantities and Units. Quantities and units for electrophoresis in the clinical laboratory. PMID- 1443791 TI - Erythrocyte metabolic alterations in type I diabetes: relationship to metabolic control. AB - Erythrocytes from young type I diabetic patients (n = 11), incubated in their plasma in anaerobic conditions, exhibited higher glucose consumption than cells from controls (n = 11). This increased metabolic activity is believed to reflect erythrocyte alterations dependent on the degree of metabolic control, as glucose consumption was significantly correlated to glycosylated haemoglobin (HbA1) and to glucose levels (P < 0.05 and P < 0.01 respectively). Red cell hexokinase (HK) and pyruvate kinase (PK) activities were similar in both groups whereas phosphofructokinase (PFK) activity was slightly higher in patients' cells (P < 0.05). No difference was found between patients and controls for red cell ATP and 2.3 diphosphoglycerate (2.3 DPG) levels. However, the concentrations of these glycolytic products seem also closely related to the glucose homeostasis in diabetes. Indeed, within the diabetic group, ATP levels showed a negative relationship with glucose level (P < 0.05) and 2.3 DPG a positive relationship with HbA1 (P < 0.05). In conclusion, higher glycolytic activity is present in young diabetic red cells. This activity as well as ATP and 2.3 DPG levels are related to the degree of short- or long-term diabetic control. These findings stress the importance of a careful metabolic control to avoid haematological disturbances. PMID- 1443792 TI - [Rapid identification of Candida albicans: evaluation of "Rapidec albicans". Study of 444 yeast strains]. AB - Rapid identification of Candida albicans is of great importance as it is the most frequently isolated yeast pathogen. Rapidec albicans, a new 2-h micromethod, performs two fluorescent enzymatic activities: hexosaminidase and proline arylamidase. A total of 444 yeast strains (334 from type culture collections and 110 from recent clinical isolates) were tested. The sensitivity was 98.5% and the specificity 95.8%. When only considering the clinical strains, 47/47 Candida albicans were identified by Rapidec albicans (sensitivity 100%) but only 43/47 by the germ tube test (sensitivity 91.5%). The specificities of the two tests were respectively 98.2% and 100%. This new system is therefore very efficient for the routine diagnosis of Candida albicans in the clinical field. It is easier and quicker than the germ tube test. PMID- 1443793 TI - [Electrophoresis of biological fluids with low protein concentration: application to the cerebrospinal fluid]. PMID- 1443794 TI - [Metabolism of amino acids and urea cycle: animal models of enzymopathies]. AB - This article is a review of the animal models which have been described until now for the inborn errors of amino acid metabolism and urea cycle. Two approaches have been explored to obtain such animal models: firstly oral or parenteral administration of the amino acid(s) accumulated in some enzymatic defects of the amino acid catabolism or urea cycle--specific enzymatic inhibitors have sometimes been used; secondly, the genetic approach, which is often the best method. Systematic screening of rat or mouse mutants obtained by experimental mutagenesis was performed in some cases. The relationships between the metabolic disturbances observed either in the inborn errors of metabolism or in the experimental models are discussed as well as the origin of the discrepancies often observed between human and animal syndromes. PMID- 1443795 TI - [Optimization of a spectrophotometry assay of total and oxidized blood glutathione: comparison with a fluorimetric method]. AB - We developed a method for the enzymatic assay of glutathione which is easy to practice, rapid, specific, based on the reaction of the thiol group of glutathione with dithiobis-nitrobenzoic acid after the action of glutathione reductase in the presence of NADPH. This spectrophotometric technique allowed, on the one hand, the determination of total glutathione and on the other hand, that of oxidized glutathione (disulfide), after the blockage of reduced glutathione by 2-vinyl-pyridine. The improvements of the assay of blood glutathione concerned the sample preparation, the reaction sensitivity, thanks to a better definition of the optimal pH and a reduction ot the blockage time by 2-vinyl-pyridine in well defined operating conditions. We compared the performances of our technique with a fluorimetric method. We used our method for the determination of total and oxidized blood glutathione in a control population. PMID- 1443796 TI - [Determination of mannitol and lactulose in urine by capillary gas chromatography]. AB - Gas capillary chromatography (GCC) determination of mannitol and lactulose in urine after oral intake is a method for assessing the intestinal permeability in various bowel diseases. The method proposed, using gas capillary chromatography with flame ionization detection after silylation of urine residue, gives good results: coefficients of variation varied from 6 to 8.7% for mannitol and 7.5 to 13.7% for lactulose. Detection limit was 5 mg/l for both compounds. PMID- 1443797 TI - [Serum creatinine assay: results of a multicentric study with 16 analytical systems]. AB - During a multicenter evaluation, 16 methods for creatinine measurement have been tested according to the guidelines of the Societe francaise de biologie clinique (SFBC) protocol. Kinetic Jaffe methods, widely used in France, performed on different analytical systems (Astra Beckman, IL 508, RA 1000 Technicon, Hitachi 704, 705, 717 Boehringer, Fara Roche, Progress Kone, Kem-O-Mat Coulter, Perspective France Monitor) have been compared to a continuous flow method with aqueous standards, to enzymatic methods using creatinine amidohydrolase with a colorimetric measurement (Boehringer and Ektachem Kodak) and to an HPLC method. Reproducibility, estimated with four different control sera, proved to be unsatisfactory in some cases as compared to current criteria for imprecision (less than +/- 10 mumol/l for intralaboratory and less than +/- 20 mumol/l for interlaboratory imprecision). The same selected patients sera covering the whole range of physiopathological concentrations have been analyzed with each method, and compared with the continuous flow results. Differences are more dependent on the sample than on the calibrators. The influences of haemolysis, bilirubin, acetoacetate, albumin, lipids, glucose, and some cephalosporins have been evaluated with spiked human sera. Haemolysed, turbid and jaundiced patient samples have been analyzed as well. The results vary according to the analytical procedure. This study took place in the implementation of a selected method for routine purpose with special regards to interferences and an acceptable imprecision. The method must satisfy the physicians' demands in the renal function exploration, especially in kidney-transplant patients. PMID- 1443798 TI - [Malaria in the Dunkerque hospital center from December 1979 to December 1990]. AB - Seventy-one cases of malaria were diagnosed in the hospital of Dunkerque from 1979 to 1990. Forty-five patients have been infected in the Comores islands. Among the 24 other imported cases, 17 (71%) have been contaminated in Western or Central Africa. One case of congenital malaria and one of malaria acquired by blood transfusion are also reported. Plasmodium falciparum was detected in 84.5% of the patients. The four human species were found among the Comorians. Two cases with abnormal forms of Plasmodium vivax were observed. PMID- 1443799 TI - [Perforation of the esophagus during attempted endotracheal intubation]. AB - A case is reported of oesophageal perforation which occurred during an attempt to carry out endotracheal intubation. A 54-year-old female patient was scheduled for mastectomy. She had no clinical features likely to predict a difficult endotracheal intubation. After induction with thiopentone, phenoperidine and suxamethonium, three attempts were made to carry out tracheal intubation with a Mallinckrodt Lo-pro tube, internal diameter 7.5 mm. During the third attempt, the oesophagus was accidentally intubated. The diagnosis was made before any insufflation was carried out. Another anaesthetist took over, and intubated the patient. At that time, there was left-sided cervical emphysema which quickly spread. An oesophageal perforation was suspected, and the patient was given 500 mg of metronidazole and 1 g of cefotetan. Postoperatively, the antibiotics were continued, and the patient had nothing by mouth. Oesophagography showed a posterior fistula in the upper third. Conservative treatment was continued until the seventh day, when another oesophagography was carried out. This showed that the perforation had completely healed. This rather rare complication of endotracheal intubation may have a poor prognosis if it results in mediastinitis. The diagnosis and prognosis of this complication and its treatment, whether conservative or surgical, are discussed. PMID- 1443800 TI - [Pulmonary pasteurellosis in a young patient with multiple trauma]. AB - A case is reported of an 18-year-old male patient who had a road traffic accident, with head and chest injuries. The patient was admitted to the surgical intensive care unit 24 h later because of an alteration of his level of consciousness. He required artificial ventilation. Five days later, he developed right-sided lower lobe pneumonia, treated with positive end-expiratory pressure. A Gram negative organism was found on bronchial brushing, but not in haemocultures. It was identified as Pasteurella multocida, sensitive to beta lactamines, but not to amikacin. Cefotaxime, which had been started immediately after the arrival of the Gram stain result, was continued. Artificial ventilation was discontinued on day 12, and the patient left the unit on day 15. The patient was probably a P. multocida carrier, being in close contact with animals before his accident. This bacteria is often found in infected animal bite wounds. Pneumonia due to this bacteria usually occurs in immunodepressed patients, which was not the case here. PMID- 1443801 TI - [Fatal poisoning caused by African viper's bite (Echis carinatus)]. AB - The case is reported of a 44-year-old European who was bitten on the foot in Djibouti, probably by an African viper. Unusually, there wasn't any pain, nor any cardiovascular collapse nor any local swelling. An oedema of the lower limb started the day afterwards. Two days after the bite, the patient presented a generalized haemorrhagic syndrome, which led to his admission. There was a consumption of fibrinogen and prothrombin, without any decrease in the platelet count. Heparin was started (100 IU.kg-1.day-1), as well as fluid replacement (albumin, fresh frozen plasma, packed red cells). This allowed him to be transferred to France, where he arrived in anuria, with hyperpyrexia, and severe lower limb oedema and a haemorrhagic syndrome. There was a major extensive retroperitoneal haematoma spreading to the perineum. The four limbs were ischaemic. The patient's condition continued to worsen, developing hypoxic pulmonary oedema. He died on the seventh day after the bite, during a session of haemodialysis, from cardiovascular failure resistant to all the usual drugs. The principles of anti-venom therapy are recalled. Indeed, this should be started early enough and relies on large amounts of serum (greater than 50 ml). PMID- 1443802 TI - [Cardiac herniation and sub-herniation. Complication of intrapericardial pneumonectomy]. AB - Two cases are reported of cardiac herniation complicating intrapericardial pneumonectomy in the early postoperative period. Both patients had a radical pneumonectomy for right-sided bronchial carcinoma invading, in one patient, the carina and the superior vena cava. The pericardial defect, made necessary by the surgical procedure, had not been closed in either patient. About two hours after the end of surgery, both patients, lying supine, developed a state of shock, with tachycardia and arterial hypotension. The diagnosis of cardiac herniation was made in both cases on the chest film. Placing the patient on his left side was only partly efficient in one patient, slowing the heart rate from 160 b.min-1 to 120 b.min-1 and increasing the systolic blood pressure (from 60 mmHg to 80 mmHg). Both patients therefore required to be operated on again. In one patient, the heart had completely herniated through the pericardial defect, and had turned to the right side about the vena caval axis; in the other patient, partly improved by being turned to his left, the heart had returned to its normal position. The pericardial defects were closed in both cases with a strip of dura mater previously treated with 2 (ethyl-mercurithiol-5-benzoxazol) carboxylic acid. The immediate postoperative course was uneventful. Unexpected symptoms and sign occurring in the early postoperative period after intrapericardial pneumonectomy must imperatively lead to carrying out a chest X-ray. PMID- 1443803 TI - [Intravenous immunoglobulins in Guillain-Barre syndrome]. PMID- 1443804 TI - [The family physician must be involved in the follow-up of ambulatory surgery]. PMID- 1443805 TI - [Are incidents of epidural and spinal anesthesia more frequent during training?]. PMID- 1443806 TI - [Nerve block for surgery of the hip in a patient with severe aortic valve stenosis]. PMID- 1443807 TI - [ORL laryngeal mask]. PMID- 1443808 TI - [Propofol versus etomidate in short-time urologic surgery]. AB - Thirty patients, scheduled for short urological surgical procedures and ranked ASA 1 or 2, were randomly assigned to two homogenous groups. In group P, they were given a 2 mg.kg-1 bolus of propofol and 10 micrograms.kg-1 of alfentanil, followed by a continuous infusion of propofol (5 mg.kg-1.h-1) and 5 micrograms.kg 1 doses of alfentanil. In group E, they were given a 0.3 mg.kg-1 bolus of etomidate, followed by an infusion (1.5 mg.kg-1.h-1). The doses of alfentanil were the same as in group P. Further doses of either propofol (0.5 mg.kg-1) or etomidate (0.2 mg.kg-1) were used should anaesthesia prove not to be deep enough. The patients were not intubated, and breathed spontaneously. Surgery lasted a mean of 18.3 +/- 11.8 min (group P) and 18.8 +/- 9.4 min (group E). The following parameters were studied: the amount of each agent required for maintenance of anaesthesia, the duration of apnoea at induction, the quality of anaesthesia and of muscle relaxation, adverse effects (coughing, trismus, restlessness, nausea, vomiting), the time required for recovery, and its quality. In group P, there was a 27% decrease in arterial pressure, without any tachycardia or hypoxia, together with a quick recovery of excellent quality. On the other hand, in group E, there was little or no haemodynamic alteration, but there often was a trismus at induction. Hypoxia also occurred during induction with etomidate, being severe enough in one case to require tracheal intubation and artificial ventilation. The reasons for this hypoxia seemed to be the apnoea and the trismus, which tends to hinder assisted ventilation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443809 TI - [8th consensus conference on resuscitation and emergency medicine. Weaning from mechanical ventilation in adults, predominant neurologic and muscular diseases excluded]. PMID- 1443810 TI - [Impairment of deglutition reflex after prolonged intubation]. AB - This study was designed to assess the swallowing reflex after an endotracheal intubation of more than 24 h, as well as the influence of age and duration of intubation on swallowing. Twenty patients (aged 58 +/- 17 years) who had been intubated for more than 24 h were compared with fifteen others (63.1 +/- 16.7 years), who had never been intubated. All had a nasogastric tube. Swallowing was assessed after administration of 0.25, 0.5, 0.75 and 1 ml volumes of normal saline, in a random sequence, into the epipharynx through a thin catheter passing through the nostril after extubation (E0), and then at 1 (E1), 8 (E8), 24 (E24) and 48 h (E48) in the extubated patients, and once in the control patients. Swallowing responses were identified by an electromyogram of the floor of the oral cavity. The efficiency of the swallowing reflex was assessed by the delay between instillation and the first swallowing response obtained, and the number of swallows recorded during the first 15 seconds following each injection. There was a significant increase in swallowing delay in intubated patients for volumes less than 1 ml during the first three measurements. Recovery occurred for 0.5 and 0.75 ml at E24 and E48, when compared with the control group. However, delay remained increased throughout the study for 0.25 ml. The number of swallows was the same in both groups for each volume tested. There was no correlation between increased delay and age or duration of intubation. These data confirmed that prolonged endotracheal intubation impairs the swallowing reflex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443811 TI - [Analgesic effect of ibuprofen in pain after episiotomy]. AB - The relief of post-episiotomy pain was investigated in three groups of women, ranked ASA 1 or 2, using either a single dose of 400 mg of ibuprofen (n = 31), or 1 g of paracetamol (n = 28) or placebo (n = 31). Pain intensity was assessed with a visual analogic scale, a verbal scale and pain relief scores after half an hour, 1, 2, 3, 4, 5 and 6 h. The day after treatment, patients rated the quality of pain relief, and were asked whether they wished to take again the same drug for the same type of pain. In the placebo and paracetamol groups, respectively 22 and 16 patients asked for usual treatment before the sixth hour, whereas only 5 did so in the ibuprofen group (p less than 0.001). Ibuprofen was more effective after one hour than either of the other two drugs, whatever the scale or parameter used. In the ibuprofen group, the lower pain score was observed at the third hour. At six hours, the pain score did not differ from that three hours earlier. On the day after treatment, 22 patients from the ibuprofen group considered pain relief to have been good or excellent, versus 8 and 5 in the paracetamol and placebo groups respectively (p less than 0.001). Similarly, 24 patients from the ibuprofen group would accept the same drug again for the same type of pain, as opposed to 8 and 5 from the paracetamol and placebo groups respectively (p less than 0.01). The only side-effect reported was abdominal pain in one patient (placebo group).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443812 TI - [Sedation with propofol and fentanyl in patients under intensive care]. AB - This study investigated the efficacy of a constant rate infusion of propofol and fentanyl in thirty patients requiring artificial ventilation for more than 24 h. A loading dose, which differed according to the patient's age, was administered over a 30 min period: 2.5 mg.kg-1 for patients less than 50 (G1) (n = 9), 2 mg.kg 1 for patients between 50 and 60 years old (G2) (n = 9), and 1.5 mg.kg-1 for patients over 60 (G3) (n = 12). This was followed by an infusion of 3 mg.kg-1.h-1 in G1 and G2, and 2 mg.kg-1.h-1 in G3. A 1 microgram.kg-1.h-1 infusion of fentanyl was also given. The degree of sedation was assessed with the Ramsay scale before starting, after induction, and every four hours thereafter. When this proved to be insufficient, the dose of propofol was increased by 0.5 mg.kg 1.h-1 as well as that of fentanyl by 0.5 microgram.kg-1.h-1. Heart rate, mean arterial blood pressure, blood propofol, creatinine, transaminase and lipid levels, and urine output were measured before, during, and after the infusion. The blood propofol level increased during the infusion, being correlated to the doses given (r = 0.64, p less than 0.001). Sedation lasted 91.7 +/- 57.7 h. After stopping the infusion of propofol, mean recovery times were 7.5 +/- 5.9 min (G1), 11.4 +/- 11.4 min, and 14.4 +/- 13.5 min (G3) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443813 TI - [Gastroesophageal reflux with combined caudal and halothane anesthesia in children]. AB - Sixteen children, aged 2 to 5 years and ranked ASA 1, were included in this study assessing gastro-oesophageal reflux occurring under halothane anaesthesia, before and during, caudal anaesthesia. They were scheduled for surgery below the umbilicus lasting 1 to 5 h. After premedication with oral hydroxyzine (2 mg.kg-1) and intravenous atropine (10 micrograms.kg-1), induction was carried out with 3% halothane. A gastro-oesophageal pH probe was inserted via the nose after calibration at 37 degrees C. A neutral pH for the oesophageal electrode and an acid pH for the gastric one demonstrated the correct position of the probe. The pH was then registered every 4 s. The probe was left in situ until the patient left the recovery room. The caudal anaesthesia catheter was then inserted with the patient lying on his left side. Caudal anaesthesia was began with 2.5 mg.kg-1 of plain bupivacaine and 5 mg.kg-1 of plain lidocaine. When the patient was lying supine again, narcosis was maintained with 0.5% halothane and 50% nitrous oxide. A dose of 1.5 mg.kg-1 of bupivacaine was injected every 30 to 45 min. None of the children displayed any respiratory signs (coughing, dyspnoea, bronchospasm, cyanosis) during the combined anaesthetic. Two episodes of asymptomatic gastro oesophageal reflux were revealed by this method, one lasting 7 minutes and occurring during insertion of the caudal catheter, and the other, lasting 4 minutes, during recovery. There were no pulmonary sequels. There was excellent respiratory and haemodynamic stability throughout. The two episodes seemed to have been triggered off by rapid displacement of the patient and too deep an anaesthetic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443814 TI - [Effects of halogenated anesthetics on splanchnic hemodynamic in normo- and hypovolemic cirrhotic rats]. AB - The effects of 1 MAC of either halothane, enflurane or isoflurane on splanchnic haemodynamics were studied in cirrhotic rats that were either normovolaemic or hypovolaemic from haemorrhage. A group of conscious rats acted as the control group. Bile duct ligation had been carried out in all the rats four weeks previously to induce cirrhosis. At the time of the study, all the rats were anaesthetized with ether for catheterization of the left femoral artery and vein, and the left ventricle via the right carotid. The control group was allowed to awake. When the other rats started to recover, they were artificially ventilated with room air and 1 MAC of the halogenated agent. Heart rate and mean arterial blood pressure were monitored continuously. Once the animals had remained steady for one hour, 1.25 ml of blood for 100 g body weight was removed over a 10 min period. PaO2, PaCO2, arterial pH, heart rate, mean arterial blood pressure, cardiac index and regional blood flows (RBF) were measured before, and thirty minutes after the haemorrhage. Cardiac output and RBF were measured using the radioactive-labelled microsphere method. Only 32 animals were finally included, eight in each group. Splanchnic, portal and hepatic arterial blood flows were similar in conscious rats and in those receiving isoflurane or halothane, and were higher than in those receiving enflurane. The lowest splanchnic and portal venous blood flows were found in those rats receiving enflurane. After haemorrhage, these RBF decreased significantly in all groups except in the enflurane group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443815 TI - [Monochromatic infrared halogenated gas analyzer and handling errors]. AB - Monochromatic infrared gas spectrometers cannot identify volatile agents. Such an analyser (Capnomac, Datex) was tested while performing two errors: a) erroneous selection of the agent on the analyser, the vaporizer being filled with the correct agent; b) total or partial filling of the vaporizer (Vapor 19, Drager) with an incorrect agent, the analyser being set for the agent the vaporizer was specified for. Three agents were studied, halothane (H), enflurane (E) and isoflurane (I). Each experiment was made in triplicate, the vaporizer being dried out between each. In case of erroneous selection on the analyser, differences between E and I were very small. When H was erroneously selected, the concentration displayed was six times higher, and when E or I was selected instead of H, the concentration displayed was six times lower than expected. In the 3.3-3.5 m band, H transmittance was six times higher than those of E and I. The agent selection control changes the gain so as to correct for the selected agent (gain for H: 12.0, E: 2.24, I: 1.89). In case of erroneous filling of the vaporizer, the concentration displayed was always different from that expected. When E or I was delivered with an H vaporizer, the analyser being set on H, the concentration displayed was 3 to 9 times higher than the concentration that had been set. On the other hand, when H was delivered with an E or I vaporizer, the analyser being set to E or I, the concentration displayed was 4 to 8 times lower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443816 TI - [Desflurane (I 653) and sevoflurane: halogenated anesthetics of the future?]. AB - Sevoflurane is an halogenated methyl isopropyl ether. It is potent, non explosive and non flammable. It reacts with soda lime to form traces of a related ether which has not been shown to have any toxic effect on animals chronically exposed to it in a closed system. Induction of anaesthesia with sevoflurane is rapid and smooth, as predicted by a blood/gas partition coefficient of about 0.6 and an acceptable odour which allows the use of concentrations of up to 10%. Its MAC has been reported to vary between 1.7 and 2.3 vol %. Sevoflurane causes dose dependent cardiovascular and respiratory depression. Its effect on the cerebral circulation is similar to that of isoflurane. The extent of biotransformation is similar to that of enflurane, but its low solubility and rapid elimination confine this to the period of inhalation. No toxic effects on the kidneys, liver and haematopoietic system have been found. Desflurane is a fluorinated methyl ether, structurally very similar to isoflurane. It is non flammable and non explosive at clinical concentrations. It is more stable in the presence of soda lime than any of the volatile anaesthetic agents available. This agent must be delivered with a thermostated vaporizer within a closed circle system, as its boiling point is 23.5 degrees C. Desflurane is less potent than isoflurane. Its MAC has been estimated to be about 7.2 vol % in man. Desflurane did not lead to any liver, lung or kidney injury in laboratory rats, even during hypoxia and enzyme induction. Desflurane undergoes little biotransformation, although the presence of volatile metabolites or covalent tissue-bound products cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443817 TI - [Is posterior lumbar epidural space partitioned?]. AB - The anatomy of the posterior lumbar epidural space (PLES) has been extensively studied. Besides the anatomists, surgeons, radiologists and anaesthetists have taken an interest in this. However, because each one has considered the PLES from his own specialist field, descriptions are not always concordant. In particular, the reality of a medial partition in the PLES has been suggested by epidurography and intraoperative observations. Lewit and Sereghy and Luyendijk opened the debate by reporting, on antero-posterior epidurographic films, a clear-cut, medial, vertical and narrow picture which partitioned the PLES. However, this was not constant. Savolaine et al. also recognized this partition on epidurographic CT scans. During laminectomies, Luyendijk has taken photographs of a medial fold of the dura mater which appeared to hold it to the posterior vertebral arch, being collapsed on either side of the midline. He named it "plica mediana dorsalis durae matris" (PMD). Several anaesthetists considered that this could explain why epidural analgesia sometimes acted on one side only. Husemeyer and White, and Harrison et al., have tried to confirm this experimentally by making casts with polymerizing resins in cadavers. They did not get very convincing results. Blomberg also tried to see this space by epiduroscopy in the cadaver. Unfortunately, for technical reasons, his photographs were of poor quality. He, however, reported having seen each time the PMD and a band of connective tissue fixing it to the vertebral arch in the midline. However, all these anatomical studies used methods which alter the natural structures. Their results are therefore questionable. The PLES is a virtual space. Histological studies have shown that it is filled with fatty tissue between the dura and the vertebral arch. It is therefore conceivable that any liquid injected into the PLES, such as contrast medium or local anaesthetic, must push back the dura, the only tissue which can move to give it any room. The fatty tissue could therefore be compressed and take any of the shapes which have been described on epidurography. On the other hand, should it be torn, it seems this fatty tissue could make up these haphazard fibrous tracts tensed between the dura and the vertebral arch, such as described in classical anatomy, as Bonica recalled. These can be clearly seen during surgical and anatomical dissections, and during endoscopies carried out on cadavers with sufficient optical means, as opposed to the medial fibrous band fixing the dura to the vertebral arch.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1443818 TI - [Vascular effects of ketamine during anesthesia with diazepam and fentanyl]. AB - Twenty-six adults undergoing elective cardiac surgery were anaesthetized with diazepam and fentanyl (induction with 200 micrograms.kg-1 and 30 micrograms.kg-1 respectively, maintenance with incremental doses). Normothermic constant perfusion output cardiopulmonary bypass was carried out with a membrane oxygenator, haemodilution with Ringer's lactate solution, and cardioplegia with St. Thomas's Hospital solution. The patients were randomly assigned to two groups. They were given either 2 mg.kg-1 of ketamine (group 1) or placebo (5 ml of normal saline) (group 2) via the venous line of the oxygenator. The non pulsatile flow was then kept at a steady rate of 2.41 x min-1.m-2, and no other infusion or treatment was started during the study period (ten minutes). The mean arterial pressure and blood reservoir level were measured every min during this period. The systemic vascular resistances did not change significantly in either group, but remained 27% lower in the ketamine group than in the placebo group (p less than 0.01). The blood reservoir level was 37% higher in the ketamine group (p less than 0.01), suggesting a decreased venous capacitance. It is therefore concluded that ketamine leads to venous constriction, and probably arterial dilation, during fentanyl-diazepam anaesthesia and normothermic cardiopulmonary bypass. The venous effects of ketamine could explain why it is usually well tolerated in hypovolaemic states. PMID- 1443819 TI - [Penile block in adults]. AB - A block of the penile nerves provides a sensory blockade of the penis. In adults, surgery can thus be carried out on the foreskin, glans, corpus cavernosum, corpus spongiosum or penile urethra. The two dorsal nerves of the penis can be blocked by two different routes. In the median technique, only one injection is performed in the subpubic space, near the posterior inferior aspect of the symphysis. In the bilateral technique, each penile nerve is blocked separately at the level of the penile root. Whichever technique is used, additional subcutaneous infiltration of the penile root improves the quality of analgesia. Bupivacaine without adrenaline is used at a concentration of 0.25% or 0.5%. In the median technique, bilateral diffusion of the anaesthetic solution has been demonstrated in ten patients by adding contrast medium to the anaesthetic solution. On the other hand, contralateral diffusion was only found in six of ten patients after an unilateral injection. These results substantiate the value of the bilateral technique in the adult. Both techniques were used in a group of 80 patients, aged 17 to 87 years. In 47 patients no other agent was administered, while the remaining 33 had either additional sedation or a general anaesthetic. Among the latter, three had a partial failure of the block. Postoperative analgesia, which was of excellent quality, covered an average of 10 hours. Neither local nor general incident occurred. Penile block is a reliable technique for regional anaesthesia. Because it is easy to carry out, and comfortable for the patient, this technique may be suggested to adults requiring penile surgery. PMID- 1443820 TI - [Is preoperative systematic chest x-ray useful in general surgery? A multicenter prospective study of 3959 patients. ACAPEM. Association des Chirurgiens de l'Assistance Publique pour les Evaluations Medicales]. AB - In order to define which patients may not require a routine preoperative chest X ray, a prospective multicenter study was carried out. It included 3,959 consecutive fifteen, or more, year-old patients, free from any cancer, scheduled for a general or gastrointestinal surgical procedure other than thoracotomy, and had a plain chest X-ray beforehand. This investigation was prescribed before surgery, either by the surgeon or the anaesthetist. Patients were classified according to selected risk factors: age, smoking, emergency surgery, a past history of lung, heart or vascular disease, abnormal clinical findings related to the cardiovascular and respiratory systems, and a previous chest film made less than one year before. There were 2,092 patients in Group I (no risk factors), 916 in group II (one risk factor), 645 in Group III (two risk factors), and 276 in group IV (three risk factors). Three endpoints were selected: a modification of operative schedule or anaesthetic technique, a change in surgical procedure, and the diagnosis of postoperative complications. A rate of 23.2% of preoperative chest films were considered to be abnormal. This rate increased with age and the number of risk factors: 6.2% in Group I and 72.5% in Group IV. Surgical and anaesthetic procedures were modified as a result of the chest X-ray in only 0.5% of patients: 0.1% in Group I, 0.3% in Group II, 1.2% in Group III and 1.4% in Group IV. When pulmonary or cardiac complications did occur after the surgery, the preoperative chest film was of no help for making this diagnosis in more than 50% of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443821 TI - [Disclosure of protein C deficiency with pulmonary embolism followed by cardiac arrest during the recovery period]. AB - A case of unexpected cardiac arrest occurring in a 17-year-old male patient is reported. The patient had been admitted after sustaining hand trauma. A first emergency surgical procedure was carried out, followed about three weeks later by another one. No incidents occurred during or after either of these two operations. A third procedure was required about two months after the accident (free toe graft to the thumb of the left hand). The twelve-hour operation was carried out under general anaesthesia and axillary block. The patient was given intravenous heparin (800 IU.h-1) during the procedure on the arm. The patient recovered quickly, and was extubated before his transfer to the recovery room. Fifteen minutes later, the patient's heart rate decreased to 40 b.min-1, followed by a transient cardiorespiratory arrest. The suspicion of pulmonary embolism was confirmed by pulmonary scintigraphy. Thrombolysis was carried out with 2,000 IU.kg-1.h-1 of urokinase for a 72 h period, combined with continuous heparin administration (16 to 36 x 10(3) IU.day-1). The patient recovered after one week. No thrombophlebitis was found for origin of the emboli. Biological investigations carried out both before and after 10 minutes of anoxia revealed a normal fibrinolytic system, but a deficit in protein C (62% antigen, 64% activity). Two years after the episode of pulmonary embolism, the patient, still taking acenocoumarol, remained free from any sequela. Current perioperative management of patients with a known protein C deficit is discussed. PMID- 1443822 TI - Bioelectrodes. In honor of Dr. H.P. Schwan's 40 years of scientific research. PMID- 1443823 TI - A brief history of bioelectrodes. AB - The history of bioelectrodes is intimately associated with electrochemistry in general, through studies on electrode polarization. Electrode polarization was first recognized and studied in the early 1800s, and scientific studies in this area have continued since that time. Experimental and theoretical work on bioelectrodes, electrode polarization, and relevant electrochemistry of electrode phenomena, is traced from 1826 to Schwan's recent electrode work. PMID- 1443824 TI - Linear and nonlinear electrode polarization and biological materials. AB - Electrode polarization is a major nuisance while determining dielectric properties of cell and particle suspensions and tissues, particularly at low frequencies. Understanding of these interfacial phenomena and appropriate modelling are essential in order to correct for its distortion of the dielectric properties of the sample of interest. I survey the following topics, concentrating on contributions from our laboratory: Linear properties of electrode polarization and relevant models. Effects of electrode polarization on sample impedance. Effects of sample on polarization impedance. Techniques of correction. Extension of linear to nonlinear models Harmonics generated in the nonlinear range. PMID- 1443825 TI - Impedance spectroscopy. AB - Impedance spectroscopy (IS) is a general term that subsumes the small-signal measurement of the linear electrical response of a material of interest (including electrode effects) and the subsequent analysis of the response to yield useful information about the physicochemical properties of the system. Analysis is generally carried out in the frequency domain, although measurements are sometimes made in the time domain and then Fourier transformed to the frequency domain. IS is by no means limited to the measurement and analysis of data at the impedance level (e.g., impedance vs. frequency) but may involve any of the four basic immittance levels: thus, most generally, IS stands for immittance spectroscopy. PMID- 1443826 TI - A physical interpretation of Schwan's limit current of linearity. AB - In this the second of a series of papers on the nonlinearity of the electrode electrolyte interface impedance, the wealth of experimental observations which exists in the literature on AC impedance nonlinearity is physically interpreted. The interface impedance is well represented by the parallel combination of a constant phase angle impedance and a charge transfer resistance. The charge transfer resistance is the major source of the observed nonlinearities. As a result, the current limit of linearity, iL, increases with frequency such that iL is proportional to omega beta. The series resistance, Rs, of the interface impedance initially increases with applied signal amplitude, reaches a maximum and then decreases. The series reactance, Xs, decreases monotonically with signal amplitude. PMID- 1443827 TI - Analysis of polarization dynamics by singularity decomposition method. AB - The driving point immittance (impedance or admittance) function is commonly used in electrical characterization of polarized materials and interfaces. The immittance function typically attenuates following a power function dependence on frequency. This fact has been recognized as a macroscopic dynamical property manifested by strongly interacting dielectric, viscoelastic and magnetic materials and interfaces between different conducting substances. Linear interfacial polarization processes which occur at metal electrode-electrolyte interfaces have been represented by the Fractional Power Pole [FPP] function in single or multiple stages. The FPP function is referred to as the Davidson-Cole function in the dielectrics literature. A related function widely used in mathematical modeling of dielectric and viscoelastic polarization dynamics is the Cole-Cole function. The fractional power factor which parametrizes the FPP or the Davidson-Cole function has been shown earlier to equal the logarithmic ratio of the locations of the pole-zero singularities. In this paper we first review a modified form of the singularity decomposition of the FPP function accomplished within a prescribed error range. The distribution spectrum and the corresponding simulation by a cascade R-C network, as opposed to the synthesis by a ladder R-C network, are readily obtained as the next step in the simulation. The method is then applied to decompose the Cole-Cole function; the pole-zero placement of the singularity function is determined and the equivalent cascade R-C network is synthesized. PMID- 1443828 TI - The admittance of the interface between a metal electrode and an aqueous electrolyte solution: some problems and pitfalls. AB - Electrochemical admittance measurements have become popular as a convenient, non invasive method for the study of interfacial properties of the metal-solution interface. However, uncritical use of this technique (as of any other) can lead one astray. Here, then, some of the complicating factors and common problems will be discussed. PMID- 1443829 TI - Electrode-electrolyte interface impedance: experiments and model. AB - The impedance of the junction between a solid or aqueous electrolyte and a metal electrode at which no charge transfer processes occur (blocking contacts) follows closely the constant phase angle form, Z = A(j omega)-n, over a wide frequency range, where A is a constant, and the frequency exponent n is typically in the range of 0.7 to 0.95. Several models have been proposed in which the magnitude of the frequency exponent n is related by a simple expression to the fractal dimension d of the rough electrode surface. But experiments with aqueous H2SO4 and roughened platinum and silicon electrodes show that there is no simple relationship, if any at all, between n and d when d is determined from the analysis of one dimensional surface profiles. Moreover, n is not a simple function of the average roughness of the electrode. In order to gain some insight into the effect of electrode topography and the interface impedance, a model for the response of the interface to a constant voltage pulse was constructed. This model is based on the idea that, following a pulse, locally concentrated regions of ions accumulate rapidly at the tips of large protrusions on the electrode surface which screens deeper regions of the electrode from the field driven flux of mobile ions. After this rapid charging, ions are able to reach the deeper, screened regions of the electrode by diffusion, and it is this diffusive process that gives rise to the observed t1-n dependence of the charge collected. Computer simulations, similar to the diffusion limited aggregation model, using measured profiles as fixed (non-growing) clusters, gave exponents n in good agreement with experiment. PMID- 1443830 TI - Impedances of thin and layered systems: cells with even or odd numbers of interfaces. AB - Impedance data, e.g., system responses, from perturbing small amplitude applied sinusoid signals of near DC to high kilohertz frequencies, give chemical information. Analysis of frequency-dependent imaginary and real impedance proceeds from equivalent analog circuit elements to chemical and physical significance determined from many model systems. Already, it is possible to interpret bulk transport processes, surface kinetic effects, diffusion phenomena, and dependencies on the type of contacts: symmetric ion contact, symmetric metal contact or asymmetric metal-ion interfaces, and cell design; even (battery or sensor) and odd numbered (constrained junction or immiscible liquid) interfaces in a system. These analyses cover the chemical origins, locations and meanings of the lumped resistances, capacitances and transmission lines that are introduced by engineers in their strict analog interpretations of the impedance data. Examples cover simple ohmic, simple diffusive behavior, complex behavior with surface interfacial kinetics or surface resistances, and with finite (nonblocking) or infinite (blocking) DC impedance. High and low frequency responses may show so-called constant phase element character that suggests fractal behavior. Low frequency data occasionally appear in the second quadrant of impedance plane plots. These results are caused by negative capacitances and resistances. In this paper, chemical interpretations of analog circuit elements are mainly based on theory and observations of thin cells of electrolytes and solid and liquid films (membranes) that are ionic or mixed ionic/electronic conductors. The information should carry over into thickened, gelled, and tissue electrolyte phases and serve as a basis for medically-oriented, perhaps diagnostic impedance measurement applications already pioneered by Herman Schwan. PMID- 1443831 TI - Electrode recovery potential. AB - In some instances the same electrodes are used for stimulation and then for recording a bioelectric event immediately after the stimulus. However, after the current pulse there remains an electrode potential that decays quasiexponentially. We have designated this falling potential the electrode recovery potential. This study investigated the recovery potentials of single electrodes of rhodium, stainless steel, platinum and platinum-iridium in contact with 0.9% saline at room temperature (25 degrees C) over a current density ranging from 0.1 to 100 mA/cm2 using a constant-current pulse. In all cases, with increasing current density, there was a decrease in the time for the electrode potential to fall to one half of the immediate post-stimulus value. Above about 20 mA/cm2 the decrease in recovery time was smooth with increasing current density. Below 20 mA/cm2, the recovery time was slightly irregular. The shortest recovery times were for platinum and platinum-iridium. The largest decrease in recovery time with increasing current density was for stainless steel, which decreased 10 fold from 0.1 to 100 mA/cm2. The recovery time for rhodium decreased about three-and-one half fold over the same current density range. It was found that the waveform of the recovery potential is not a simple exponential because the Warburg and Faradic components of the electrode-electrolyte interface are current-density dependent. In general, for all current densities studied (0.1-100 mA/cm2), there was a sudden initial fall in electrode potential with cessation of current flow, followed by a very gradual nonexponential decrease in potential. PMID- 1443832 TI - Biocompatibility considerations at stimulating electrode interfaces. AB - The choice of biocompatible stimulating electrodes for various biomedical applications varies with the type of electrode-tissue interface, biomolecules present, electrolyte background, preparation of electrode, interfacial potential, current density, electrode material, porosity, geometry, and inflammatory response. Illustrative examples are given to demonstrate the importance of these parameters. Topics discussed are: A) DC electrodes applied to partially keratinized epithelial membranes; B) Variation of the electrical impedance and biocompatibility of stimulating electrodes with electrode potential and surrounding pH; C) Influence of electrode geometry, porosity and pore size on biocompatibility; D) Body defense mechanisms at the sites of implantable stimulating electrodes; E) Thrombus formation at stimulating electrode interfaces and F) Sterilization of electrodes to ensure biocompatibility. PMID- 1443833 TI - Utility of serum interleukin-6 for diagnosis of invasive bacterial disease in children. AB - STUDY OBJECTIVE: To evaluate measurement of interleukin-6 as a diagnostic test for the presence and severity of invasive bacterial disease. DESIGN: Prospective measurement of interleukin-6 in children with signs of sepsis. (Controls, retrospective from serum bank.) SETTING: Emergency department of an urban children's hospital. PARTICIPANTS: Twenty children with clinical signs of sepsis and 50 other febrile infants and toddlers with negative blood cultures. RESULTS: Eleven of the 20 patients had bacteriologically documented infections: four with meningitis and two with bacteremia caused by Neisseria meningitidis, three with meningitis caused by Haemophilus influenzae type b, and one each with meningitis and bacteremia caused by Streptococcus pneumoniae. Ten of these 11 had detectable interleukin-6. The geometric mean interleukin-6 level in these culture-positive patients was 407 pg/mL (95% confidence interval, 108 to 1,545); all three children with levels of more than 300 pg/mL developed septic shock, and one died. One of nine culture-negative patients with clinical signs of sepsis had detectable serum interleukin-6 (166 pg/mL), but none of 50 other febrile children without occult bacteremia did. The detection of interleukin-6 had a sensitivity of 91% and a specificity of 98% for invasive bacterial disease. CONCLUSION: High levels of interleukin-6 occur in children with septic shock, and the presence of interleukin-6 in serum is predictive for the isolation of bacteria from blood and/or spinal fluid. PMID- 1443834 TI - Septic arthritis versus transient synovitis of the hip: the value of screening laboratory tests. AB - STUDY OBJECTIVE: To determine the diagnostic value of screening laboratory and initial body temperature data in differentiating septic arthritis of the hip from transient synovitis of the hip in children who present to the emergency department with a complaint of hip pain. DESIGN: Retrospective review of cases of septic arthritis of the hip and transient synovitis of the hip in a 1:2.5 ratio. SETTING: An urban regional children's hospital with 20,000 annual ED visits. RESULTS: Ninety-four children with transient synovitis of the hip and 38 children with septic arthritis of the hip were identified. The children with septic arthritis of the hip had a significantly higher initial temperature (38.1 C versus 37.2 C, P = .000014), mean erythrocyte sedimentation rate (44 mm/hr versus 19 mm/hr, P = .000001), and mean WBC count (13,200/mm3 versus 11,200/mm3, P = .02). However, the degree of overlap in these variables was large. The combination of an erythrocyte sedimentation rate of more than 20 mm/hr and/or a temperature of more than 37.5 C identified 97% of all cases of septic arthritis of the hip. CONCLUSION: There is clinically significant overlap in the erythrocyte sedimentation rate, temperature, and WBC count in children with septic arthritis of the hip versus transient synovitis of the hip. All children with an irritable hip without a clearly identified source who have an erythrocyte sedimentation rate of more than 20 mm/hr or a temperature of more than 37.5 C should be considered for diagnostic hip aspiration. PMID- 1443835 TI - Plain abdominal radiography in the detection of major disease in children: a prospective analysis. AB - STUDY OBJECTIVE: To prospectively evaluate previously described high-yield clinical criteria for obtaining plain abdominal radiographs in the emergency evaluation of children. DESIGN: Prospective, observational study. SETTING: Emergency departments of a university medical center and an affiliated county hospital. PARTICIPANTS: Three hundred fifty-four children 15 years old or younger who underwent plain abdominal radiography during a one-year period. METHODS AND MEASUREMENTS: Physicians ordering plain abdominal radiographs completed data forms that included historical and physical examination information before viewing films. At a later date, records of all patients were reviewed for radiologist interpretation and final diagnosis. The data were analyzed to determine the sensitivity, specificity, and predictive values of previously described high-yield criteria (from a retrospective series) in detecting radiographs that were diagnostic or suggestive of "major" abdominal disease. MAIN RESULTS: Sixty-one patients (17%) had major diseases potentially requiring procedural intervention (eg, appendicitis, ingested foreign bodies, and intussusception), whereas 296 patients (83%) had minor diseases not requiring procedural intervention (eg, gastroenteritis and nonabdominal diagnoses). The presence of any of the following features--prior abdominal surgery, foreign body ingestion, abnormal bowel sounds, abdominal distention, or peritoneal signs--was 93% sensitive and 40% specific in detecting diagnostic or suggestive radiographs in patients with major disease. Positive and negative predictive values were 11% and 99%, respectively. If only these criteria had been used to obtain radiographs, 38% of films would have been omitted (at an estimated savings of $20,000) with only two suggestive radiographs missed. CONCLUSION: Our results suggest that restricting abdominal radiographs to patients with at least one of these five high-yield clinical features will detect most diagnostic and suggestive radiographs in children with major abdominal diseases. PMID- 1443836 TI - Prehospital intravenous access in children. AB - STUDY OBJECTIVE: To examine the ability of a unified metropolitan paramedic system to provide IV access in children when indicated. DESIGN: Retrospective, descriptive clinical study. SETTING: A large metropolitan area in Canada. PARTICIPANTS: Five hundred thirteen children from birth through 18 years of age who were transported by paramedics. MEASUREMENTS: Indications for IV access, rates of successful placement, and time to achieve access were determined. Criteria for IV line placement were developed and applied retrospectively. MAIN RESULTS: Intravenous line attempts were made in 300 children (58%). Intravenous line placement was obtained in 253 (84% of the patients attempted). One hundred fifty-nine children met criteria for IV placement in the field. Six of these children were clinically dead and received no on-scene resuscitative efforts and were excluded from data analysis. Of the remaining 153 children who met criteria, 122 (80%) had IV attempts made, and 104 (68%) had an IV line placed successfully. For children who met the criteria for IV placement, a significantly smaller proportion of children younger than 6 years had an IV line placed successfully (49%) compared with children 6 years or older (75%) (P < .005). Two subgroups of children who met criteria were examined: children with vital signs absent and trauma patients. For those who belonged to the subgroup with vital signs absent, a significantly smaller proportion of children younger than 6 years had an IV line placed successfully (43%) compared with children 6 years or older (92%) (P < .01) Eighty-four percent of patients who met criteria and who had one IV line successfully placed received only one IV line attempt, and 87% of patients who met criteria and who had two IV lines placed successfully received only two attempts. CONCLUSION: Although paramedics had an 84% success rate at establishing IV lines in children in the field, half the children younger than 6 years who required intravascular access did not receive an IV line in the prehospital setting. Multiple IV line attempts should be discouraged because additional attempts yield little benefit and may prolong transport times. PMID- 1443837 TI - Adrenaline-cocaine gel topical anesthetic for dermal laceration repair in children. AB - STUDY OBJECTIVE: To evaluate the anesthetic efficacy of a gel form of adrenaline cocaine topical medication for minor dermal laceration repair. DESIGN: Unblinded, prospective. SETTING: An urban pediatric emergency department. TYPE OF PARTICIPANTS: Thirty-five children aged 20 months to 18 years with lacerations of the face, outer lip, and scalp. INTERVENTIONS: All received adrenaline-cocaine gel made by mixing 1.5 mL of conventional adrenaline-cocaine liquid (adrenaline, 1:2,000; cocaine, 11.8%) with 0.15 g of methylcellulose powder (an inert emulsifying agent). MEASUREMENTS AND MAIN RESULTS: Lacerations were located on the face or outer lip in 25 patients and on the scalp in ten patients. Larger lacerations (length of more than 5 cm and/or depth of more than 5 mm) occurred in nine patients. The average dose of adrenaline-cocaine gel applied per laceration was 0.35 mL (containing 40 mg cocaine). One hundred ninety-five sutures were placed (175 cutaneous, 20 subcutaneous); 192 (98.5%) were placed without eliciting any pain. There were no observed adverse reactions with adrenaline cocaine gel administration or reported complications of wound healing in any patient. CONCLUSION: Adrenaline-cocaine gel preparation provides excellent anesthetic efficacy for minor dermal lacerations in children. Compared with conventional adrenaline-cocaine liquid, adrenaline-cocaine gel may be advantageous in reducing the total cocaine requirement and may diminish the risk for adverse reactions that can result from runoff of liquid medication onto mucosal or ocular surfaces. PMID- 1443838 TI - Analysis of the clinical variables driving decision in an artificial neural network trained to identify the presence of myocardial infarction. AB - STUDY OBJECTIVE: To determine which clinical variables drive the output of an artificial neural network trained to identify the presence of myocardial infarction. DESIGN: Partial output analysis. SETTING: Tertiary university teaching center. PARTICIPANTS: Seven hundred six patients more than 18 years old presenting with anterior chest pain. MEASUREMENTS: Differential network output analysis. MAIN RESULTS: A methodology was developed as the first step in measuring the impact input clinical variables have on the output (diagnosis) of an artificial neural network trained to identify the presence of acute myocardial infarction. The methodology revealed that the network used the presence of ECG findings, as well as the presence of rales, syncope, jugular venous distension, response to trinitroglycerin, and nausea and vomiting, as major predictive sources. Although this first-step analysis studied individual variables, it must be stated that the network comes to clinical closure based on the settings of all variables in a pattern and that the impact of a single variable cannot be taken out of the context of a pattern. CONCLUSION: An artificial neural network trained to recognize the presence of myocardial infarction appears to place diagnostic importance on clinical variables that have not been shown previously to be highly predictive for infarction. PMID- 1443839 TI - Serial ECGs are less accurate than serial CK-MB results for emergency department diagnosis of myocardial infarction. AB - HYPOTHESIS: Serial creatine kinase-MB (CK-MB) levels provide more accurate predictive information regarding myocardial infarction than serial ECGs in emergency department patients with chest discomfort and no ST-segment elevation on the initial ECG. DESIGN: Prospective, observational study. SETTING: University hospital and university-affiliated Veterans Affairs Medical Center EDs. PARTICIPANTS: Two hundred sixty-one patients 30 years or older with chest discomfort warranting an ECG and consenting to observation. Exclusions included hemodynamic or rhythm instability and ST-segment elevation of 0.1 mV or more in two or more electrically contiguous leads at presentation. MEASUREMENTS: ECGs were obtained at presentation and three to four hours after presentation. Significant serial ECG changes sought on comparison of initial and three- to four hour ECGs were 0.05 mV or more ST elevation or depression, Q-wave development, or T-wave inversion changes in two or more electrically contiguous leads. CK-MB levels were obtained at presentation and hourly for three hours (positive level, 8 or more ng/mL). Myocardial infarction was determined by record review and was based on independent CK-MB measurements. RESULTS: Twenty-eight (11%) patients were diagnosed with a myocardial infarction. Thirty-eight (15%) patients had a serial ECG change. Eleven of the myocardial infarction patients (39%) had a serial ECG change compared with 27 (12%) of the non-myocardial infarction patients (P < .001). Sensitivities and specificities of a serial ECG change versus serial CK-MBs for myocardial infarction were 39% versus 68% (sensitivity) and 88% versus 95% (specificity), respectively. Serial CK-MBs were more accurate than a serial ECG change for predicting myocardial infarction (P < .03). CONCLUSION: Serial changes in ECGs during a three- to four-hour interval were associated with the diagnosis of myocardial infarction but were infrequent and less accurate than serial CK-MB levels obtained for the same interval. PMID- 1443840 TI - Efficacy and safety of transcutaneous low-impedance cardiac pacing in human volunteers using conventional polymeric defibrillation pads. AB - STUDY OBJECTIVES: To assess the safety and efficacy of transcutaneous cardiac pacing using low-impedance defibrillation-type, self-adhesive polymer electrode pads positioned in the same anatomic sites typical of such pad placement in emergency defibrillation attempts. DESIGN: Prospective, randomized, single blinded normal subject investigation. METHODS: Thirty healthy unmedicated adult volunteers of both sexes were paced transcutaneously to the threshold of capture and beyond by an intensity factor of 125%. A commercial defibrillator-pacer operating in demand mode had its rate set-point higher than the subjects' base line rate by 125%. Threshold was established as the pulse current required to effect 75% captured beats. Pacing was continued at the 125% level for two minutes, during which subjective discomfort levels were recorded on a 1-to-5 pain scale. RESULTS: All subjects but one were able to complete the study as designed. The single exception complained of intolerable pain early in the two-minute trial. Capture current had a mean value of 80 mA while the pain assessment averaged 3.2 on our five-point scale. No subject showed any untoward cardiovascular effects either during or after the study. CONCLUSION: In normal human volunteers, transcutaneous cardiac pacing with low-impedance polymer pad electrodes is safe. By extrapolation from this study population, it is sufficiently effective to accommodate successfully the vast majority of clinical circumstances likely to be encountered in emergency medicine. PMID- 1443841 TI - Low-risk criteria for cervical-spine radiography in blunt trauma: a prospective study. AB - STUDY HYPOTHESIS: Cervical-spine radiography does not need to be performed on selected blunt trauma patients who are awake, alert, nonintoxicated, do not complain of midline neck pain, and have no tenderness over the bony cervical spine. STUDY POPULATION: One thousand consecutive patients seen in the UCLA Emergency Medicine Center with a chief complaint of blunt trauma, for whom cervical-spine films were ordered and for whom prospective data questionnaires were completed. METHODS: Clinicians completed data forms for each patient before radiograph results were known. Data items included mechanism of injury, evidence of intoxication, presence of cervical-spine pain and/or tenderness, level of alertness, presence of focal neurologic deficits, and presence of other severely painful injuries unrelated to the cervical spine. Physicians were also asked to estimate likelihood of significant cervical-spine injury. RESULTS: Twenty-seven patients with cervical-spine fracture were among the 974 patients for whom data forms were completed. A number of findings were statistically more common in the group of patients with fracture than without, but no single or paired findings identified all patients with fracture. All 27 patients with fracture had at least one of the following four characteristics: midline neck tenderness, evidence of intoxication, altered level of alertness, or a severely painful injury elsewhere. Three hundred fifty-three of 947 (37.3%) patients without cervical-spine fracture had none of these findings. CONCLUSION: Cervical-spine radiology may not be necessary in patients without spinous tenderness in the neck, intoxication, altered level of alertness, or other severely painful injury. A policy to limit films in such patients would have decreased film ordering by more than one third in this series, while identifying all patients with fracture. PMID- 1443842 TI - What is a neural network? PMID- 1443843 TI - New horizons: emergency medicine at sea. PMID- 1443844 TI - Incidence of agonal respirations in sudden cardiac arrest. AB - STUDY OBJECTIVE: To discover the frequency of agonal respirations in cardiac arrest calls, the ways callers describe them, and discharge rates associated with agonal respirations. DESIGN: We reviewed taped recordings of calls reporting cardiac arrests and emergency medical technician and paramedic incident reports for 1991. Arrests after arrival of emergency medical services were excluded. SETTING: King County, Washington, excluding the city of Seattle. PARTICIPANTS: Four hundred forty-five persons with out-of-hospital cardiac arrests receiving emergency medical services. INTERVENTIONS: Telephone CPR, emergency medical technicians-defibrillation, and advanced life support by paramedics. MEASUREMENTS AND MAIN RESULTS: Any attempts at breathing described by callers were identified, as well as whether agonal respirations could be heard by dispatcher, emergency medical technicians, or paramedics. Agonal respirations occurred in 40% of 445 out-of-hospital cardiac arrests. Callers described agonal breathing in a variety of ways. Agonal respirations were present in 46% of arrests caused by cardiac etiology compared with 32% in other etiologies (P < .01). Fifty-five percent of witnessed arrests had agonal activity compared with 16% of unwitnessed arrests (P < .001). Agonal respirations occurred in 56% of arrests with a rhythm of ventricular fibrillation compared with 34% of cases with a nonventricular fibrillation rhythm (P < .001). Twenty-seven percent of patients with agonal respirations were discharged alive compared with 9% without them (P < .001). CONCLUSION: There is a high incidence of agonal activity associated with out-of hospital cardiac arrest. Presence of agonal respirations is associated with increased survival. These findings have implications for public CPR training programs and emergency dispatcher telephone CPR programs. PMID- 1443845 TI - Prevention of hyperbaric-associated middle ear barotrauma. AB - STUDY OBJECTIVE: To determine the efficacy of topical nasal decongestant in the prevention of middle ear barotrauma in patients undergoing hyperbaric oxygen therapy. DESIGN: Prospective, parallel, double-blind, randomized trial. SETTING: University-affiliated community hospital emergency department with hyperbaric oxygen facilities. PARTICIPANTS: Sixty patients undergoing hyperbaric oxygen therapy; 30 subjects in each treatment arm. INTERVENTIONS: After randomization, consenting patients were given two sprays of oxymetazoline hydrochloride or sterile water, 15 minutes before hyperbaric oxygen therapy. Collected data included patient demographics, ear examinations before and after hyperbaric oxygen treatment, and subjective ear complaints. The otoscopic appearance of the tympanic membrane was graded according to the amount of hemorrhage in the eardrum, with Teed scores ranging from 0 (symptoms only) to 5 (gross hemorrhage and rupture). RESULTS: The treatment groups were similar with regard to age, sex, and medical history. Ear discomfort during hyperbaric oxygen therapy was present in 63% (19 of 30) of those receiving oxymetazoline versus 67% (20 of 30) of the control group (P = .99). Likewise, both groups had similar Teed scores after hyperbaric oxygen therapy (P = .88). No adverse effects were noted. CONCLUSION: The results of this pilot study suggest that topical decongestants may not be effective in preventing middle ear barotrauma during hyperbaric oxygen therapy. PMID- 1443846 TI - Use of transcutaneous electrical nerve stimulation for fingertip analgesia: a pilot study. AB - STUDY OBJECTIVES: To determine if transcutaneous electrical nerve stimulation (TENS) can produce fingertip analgesia. DESIGN: Randomized, crossover trial. PARTICIPANTS: Fifteen healthy volunteers, naive to the technique of TENS. INTERVENTIONS: TENS stimulation was applied to the middle and ring fingers of each subject's hands by means of small carbon electrodes placed over the digital nerves. Patients received one fingertip puncture from a mechanically driven sterile lancet device to each digit corresponding to one of four conditions: sham, one minute of TENS, ten minutes of TENS, and 20 minutes of TENS. The TENS unit was operated in the "burst" mode, with two eight-pulse burst groups per second (pulse width, 225 mu sec; pulse frequency, 80 Hz). The order of the conditions and the finger used for each condition were assigned randomly. The pain of each puncture was rated on a 10-cm visual-analog scale. Data were analyzed using a repeated-measures analysis of variance with Duncan's multiple comparisons procedure. MEASUREMENTS AND RESULTS: Mean visual-analog scale scores decreased sequentially from sham in each experimental condition: one minute of TENS, 24.4% (P < .025); ten minutes of TENS, 28.2% (P < .025); and 20 minutes of TENS, 55.7% (P < 10(-6)). Two patients had total anesthesia of the fingertip (visual-analog scale = 0 cm) in the 20-minute TENS condition. CONCLUSION: TENS significantly reduces the pain of lancet-induced trauma to the fingertip. Further studies are warranted to determine if this technique is useful clinically as an alternative or adjunct to digital nerve block anesthesia for fingertip surgical procedures. PMID- 1443847 TI - Shipboard medicine: a new niche for emergency medicine. AB - STUDY OBJECTIVES: To describe the spectrum of illness that presents to shipboard hospitals and thereby recommend optimal qualifications for the ship's medical personnel. DESIGN: Retrospective review of medical logs from two cruise ships' hospitals. SETTINGS: Two passenger cruise ships, with seven-to-ten day cruises in the Caribbean. PARTICIPANTS: All patients presenting to the ships' hospitals from January 4, 1989, to June 10, 1989, on one ship and from October 13, 1990, to November 10, 1990, on another ship. METHODS: Analysis of ship medical logs with regard to patient complaint, diagnosis, and treatment. RESULTS: Of 1,547 new patient visits, 12% were related to injuries and 88% to medical problems; 97% of visits were noncritical, and 3% required immediate emergency intervention. Among these were four cardiac arrests, two stab wounds, two serious ocular injuries, one closed-head injury, and one near-drowning. Five patients required endotracheal intubation. CONCLUSION: There is a sizeable number of visits to ships' hospitals by patients with acute and serious problems of a wide variety. Physicians and nurses with significant emergency training or experience are best qualified to deal with this broad spectrum of patient problems in this isolated environment. PMID- 1443848 TI - Simpson's paradox and clinical trials: what you find is not necessarily what you prove. AB - Expensive clinical trials have become the gold standard for evaluating the efficacy of promising new therapeutic agents. Full exploration of the collected data is routine to maximize the yield of the information available. However, potential methodologic flaws in these extensive analyses may not be appreciated by investigators or readers. One such problem with subgroup analyses is discussed, using hypothetical examples and data from a recently completed clinical trial of brain resuscitation as illustrations. PMID- 1443849 TI - Collapse of a young athlete. PMID- 1443850 TI - Adenosine in the treatment of paroxysmal supraventricular tachycardia in children. AB - Intravenous bolus adenosine was given to four pediatric patients aged 1 month to 8 years who had paroxysmal supraventricular tachycardia that had not responded to conventional medical therapy. Adenosine (one to three doses) was successful in converting the arrhythmia to normal sinus rhythm in all four cases, and no side effects of the drug were noted. PMID- 1443851 TI - Bilateral cortical blindness: an unusual presentation of bacterial endocarditis. AB - We report the case of a 37-year-old woman who presented to the emergency department with the initial complaint of complete blindness. The patient was found to have bilateral ruptured occipital mycotic aneurysms as a sequela of bacterial endocarditis. This case is unique in several aspects. Although blindness may be a presenting neurologic symptom, it is exceedingly rare. To our knowledge, bilateral cortical blindness secondary to mycotic aneurysm rupture has not been reported previously. PMID- 1443852 TI - Spontaneous renal artery thrombosis associated with altered mental status. AB - Renal artery thrombosis is much less common than renal artery occlusion by emboli. When it does occur, it is usually a result of blunt abdominal trauma or a thrombus superimposed on an atherosclerotic plaque. Numerous other factors have been associated with renal artery thrombosis. Spontaneous renal artery thrombosis is a rare phenomenon in itself. This case represents spontaneous renal artery thrombosis associated with an altered mental status. Clinical features with suspected etiologies are reviewed. Recommendations for future evaluations are given. PMID- 1443853 TI - Aortic saddle embolus presenting with transient lower extremity paresthesia. AB - We report the case of a 58-year-old woman who developed acute onset of bilateral lower-extremity numbness and difficulty ambulating at home. On presentation to the emergency department, however, the patient's symptoms essentially had resolved. An aortic saddle embolus was suspected based on the patient's cardiac history and the absence of distal pulses in the lower extremities. This case illustrates that even with vague or resolving complaints, a high index of suspicion should be maintained for the diagnosis of aortic saddle embolus based on the patient's medical history and on physical examination. PMID- 1443854 TI - Clinically occult presentation of comminuted intertrochanteric hip fractures. AB - Hip fractures in awake patients are rarely subtle in their clinical presentation. We report two cases of occult, comminuted, intertrochanteric hip fractures that occurred in awake, elderly patients who were brought to the emergency department for evaluation of other medical conditions. Neither patient complained of hip pain, and both were transported to the ED without spinal immobilization. Physical examination revealed no sign of hip fracture. Patient 1 was scheduled for admission and just prior to transfer out of the ED developed hip pain. Patient 2 was admitted for workup of possible transient ischemic attack and approximately 2.5 hours after admission complained of hip pain. Radiographs of both patients revealed comminuted intertrochanteric hip fractures. In an elderly, nonambulatory patient who may have fallen prior to evaluation, routine radiographs of the pelvis and hip should be performed followed by plain tomography, computed tomography, bone scan, or magnetic resonance imaging as indicated to rule out occult hip fracture. Even comminuted intertrochanteric hip fractures can present in an occult fashion; therefore, a high index of suspicion must be maintained for these injuries. PMID- 1443855 TI - Verifying endotracheal tube placement in children. PMID- 1443856 TI - Topical antibiotics for all wounds? PMID- 1443857 TI - Usefulness of a diagnostic test. PMID- 1443858 TI - Psychological factors in abortion. A review. AB - Psychological research is increasingly involved in debates regarding abortion. While recognizing the diversity of ethical and moral issues intertwined with abortion, the American Psychological Association (APA) has focused its involvement on psychological factors, most recently by appointing an expert panel to review the literature on psychological effects. This article notes the history of APA involvement and reports on the panel's conclusions. It presents evidence that abortion is not likely to be followed by severe psychological responses and that psychological aspects can best be understood within a framework of normal stress and coping rather than a model of psychopathology. Correlates of more negative responses following abortion are also discussed. PMID- 1443859 TI - Broken hearts or broken bonds. Love and death in historical perspective. AB - Psychological theories and practices frequently neglect the extent to which their subject matter is historically and culturally defined. This issue is explored in the context of theories and therapies related to bereavement. Contemporary orientations emphasize the importance of breaking bonds with the deceased and the return of survivors to autonomous lifestyles. Placing the orientation in cultural and historical context reveals that it is largely a product of a modernist worldview. Within the romanticist ethos of the preceding century, such breaking of bonds would destroy one's identity and the meaning of life. In light of contemporary variations in subcultural meanings and values, a postmodern view is suggested in which reflexive responsibility is focal. PMID- 1443860 TI - ANCAs aweigh. PMID- 1443861 TI - Effect of tidal volume on gas exchange and oxygen transport in the adult respiratory distress syndrome. AB - The effect of tidal volume (VT) on gas exchange and oxygen delivery (DO2) was studied in nine patients with adult respiratory distress syndrome (ARDS) and in 10 postoperative open-heart surgery patients (CABG). During controlled mechanical ventilation, VT was initially 10 to 12 ml/kg, followed by an increase and reduction of 25% (1.25 VT and 0.75 VT, respectively). In both groups of patients, dead space (VD) correlated strongly with VT (p < 0.001), while the VD/VT ratio was independent of VT. PaO2 tended to increase in CABG patients and decrease in ARDS patients at 1.25 VT. Arterial oxygen saturation (SaO2) did not change at 1.25 VT but decreased at 0.75 VT (p < 0.001) in the ARDS group. Venous admixture (QS/QT) decreased with 1.25 VT and increased with 0.75 VT (p < 0.001). A relatively larger increase in cardiac output compensated for the increased QS/QT and the reduced SaO2, resulting in significantly higher DO2 with 0.75 VT (p < 0.01). A lower VT resulted in improved balance between pulmonary gas exchange and whole body oxygen supply. PMID- 1443862 TI - Use of a measurement of pulmonary hyperinflation to control the level of mechanical ventilation in patients with acute severe asthma. AB - Mechanical ventilation causes significant morbidity and mortality in patients with severe asthma. Hypoventilation may reduce this morbidity and mortality, but indicators to guide the degree of hypoventilation are unclear. We used a measure of pulmonary hyperinflation to assess the degree of airflow obstruction and to guide the extent and duration of hypoventilation. Ten patients who required mechanical ventilation for acute severe asthma were studied. All were sedated, paralyzed, and given an initial minute ventilation (VE) of 200 ml/kg/min. End inspiratory lung volume (VEI) above FRC was measured from the total exhaled gas volume during 40 to 60 s of apnea. VEI was used to regulate VE to a safe level (VEsafe), irrespective of PaCO2, by reducing the rate when VEI was > 20 ml/kg and increasing it when VEI was < 20 ml/kg. Each patient was weaned when VEsafe resulted in PaCO2 < or = 40 mm Hg (the weaning point). FRC was measured computer analysis of anterior and lateral chest radiographs taken at the end of apnea. Using the weaning point criterion, 2 patients (PaCO2 < 40 mm Hg) were weaned shortly after arrival. The remaining eight (initial PaCO2, 63 +/- 17 mm Hg) continued hypoventilation until the weaning point was reached (30 +/- 29 h). The weaning point was reached by the VE required for PaCO2 40 mm Hg decreasing concurrent with the VEsafe increasing. All but 1 patient were successfully weaned within 24 h of the weaning point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443863 TI - Plasma elastin-derived peptide levels in normal adults, children, and emphysematous subjects. Physiologic and computed tomographic scan correlates. AB - Pulmonary emphysema is likely to be the result of elastic tissue digestion by unrestrained elastase activity in the lung. Elastin breakdown by elastases results in the release of soluble elastin fragments (EDP), which may be measured in plasma by an ELISA. Plasma EDP levels measured using an ELISA were determined in the following groups: disease-free children (n = 24), 0.162 +/- 0.082 ng/ml; disease-free adult nonsmokers (n = 114), 1.74 +/- 0.8 ng/ml; smokers (n = 68), 2.76 +/- 4.59 ng/ml; reformed smokers (n = 43), 1.91 +/- 1.14 ng/ml. Adults with established pulmonary emphysema (n = 50), as defined by bullous formation on the chest radiograph, had levels of 50.83 +/- 24.8 ng/ml, significantly higher than the disease-free groups at p < 0.01. Pulmonary emphysema can be reflected by pulmonary function tests, especially those that measure the pulmonary elastic properties, and by computed tomographic (CT) scan percent emphysema score. We therefore examined the relationship of plasma EDP to these other indicators of pulmonary emphysema in a separate group of 26 subjects using elastic recoil measurements (K), and a further group of 30 subjects with CT scan percent emphysema score. A significant correlation of p < 0.001 was shown for plasma EDP and K and a significant correlation of p < 0.01 was shown for plasma EDP and CT scan percent emphysema score, these correlations suggesting that plasma EDP levels are indicators of the loss of pulmonary distensibility and of mild to moderate pulmonary emphysema. These findings suggest that pulmonary emphysema is characterized by active elastin breakdown. PMID- 1443864 TI - Formoterol compared with beclomethasone and placebo on allergen-induced asthmatic responses. AB - Formoterol is a new long-acting beta 2-agonist. We compared the protective effect of 24 micrograms formoterol with 200 micrograms beclomethasone and placebo on inhaled allergen-induced asthmatic responses in mild stable asthmatic subjects. We measured airflow rates, histamine airway responsiveness, cell counts from sputum and peripheral blood, and markers of lymphocyte and eosinophil activation. Adjustments were made for the confounding effect of bronchodilatation produced by formoterol in comparisons using a control inhalation of normal saline. Formoterol caused bronchodilation and inhibition of histamine airway responsiveness for at least 24 h. It completely inhibited the early asthmatic responses when beclomethasone had no effect. Control comparisons of the effect of formoterol and beclomethasone on the allergen-induced late asthmatic response and increase in histamine responsiveness showed each to be equally effective but not to inhibit the responses completely. Formoterol caused bronchodilation in addition to preventing bronchoconstriction. Both drugs inhibited the rise in serum eosinophil cationic protein 24 h after allergen, but neither inhibited the allergen-induced increases in sputum or blood eosinophils or CD25+ lymphocytes. These results suggest that formoterol modifies allergen-induced airway responses through functional antagonism rather than the inhibition of inflammatory cell infiltration. PMID- 1443865 TI - Increased oxygen species generation in blood monocytes of asthmatic patients. AB - Besides eosinophils, inflammatory processes in asthma are characterized by an infiltration of inflammatory cells, including mononuclear phagocytes, such as alveolar macrophages (AM) and blood monocytes, in the airways. Monocyte activation has been observed in the blood after exercise or allergen-induced asthma. Stimulated AM in chronic and stable asthmatic patients have been shown to release oxygen species. We thus investigated the intensity of the activation of monocytes from 18 asthmatic patients compared with 18 healthy subjects. Oxygen species release was analyzed for monocytes in suspension by chemiluminescence using a luminometer and for monocytes maintained in adherence using conventional assay and video imaging camera. Circulating blood monocytes in suspension from asthmatic patients and control subjects showed the same baseline free radical release. Monocytes in suspension from asthmatic patients were more stimulatable by PMA: specifically, monocytes release more H2O and peaks of O2-. are sooner; moreover, peaks of total free radical release are higher, and this plateau is sustained. Compared with monocytes from control subjects, those from asthmatic patients evaluated after adherence show a higher baseline for O2-. and higher total free radical release. Monocytes from asthmatic patients spontaneously release more O2-. over time in nonstimulated cells and release more O2-. with PMA stimulation; they show the same peak level total free radical release as those from control subjects after stimulation. SOD activity analysis on adherent monocytes was lower in asthmatic compared with control subjects. These data show that monocytes from asthmatic patients were activated compared with control monocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443866 TI - Impairment of airway mucociliary transport by Pseudomonas aeruginosa products. Role of oxygen radicals. AB - We previously showed that the supernatant of a Pseudomonas aeruginosa (PA) culture and its constituents pyocyanin and 1-hydroxyphenazine inhibit ciliary activity of dispersed tracheal epithelial cells in vitro via the generation of oxygen radicals by phagocytes. In the present study, we wished to determine if tracheal mucus velocity (TMV) is also impaired by PA supernatant and if oxygen radicals have a mediating role. In conscious sheep, TMV (measured with a radiographic method) was determined before and serially following aerosol challenge with the cell-free supernatant of a PA culture or unconditioned culture medium (control). TMV decreased from a mean (+/- SEM) baseline of 6.7 +/- 1.1 mm/min (n = 6) by 29, 35, and 25% at 0.5, 3, and 24 h after challenge, respectively (p < 0.05), and returned to baseline 1 wk later (-6%, p = NS). Control medium had no effect on TMV (maximum decrease by 15% at 0.5 h). Aerosolized catalase blunted the effect of PA supernatant on TMV. To determine if the impairment of TMV involved ciliary inhibition, tissues were mounted in a chamber and ciliary beat frequency (CBF) and surface liquid velocity (SLV) were measured with a microscopic method. PA supernatant decreased both CBF (maximum mean decrease 12%; n = 5, p < 0.05) and SLV (maximum mean decrease 78%; n = 5, p < 0.05) in a dose-dependent fashion, with a correlation between the two parameters; these effects were blocked by catalase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443867 TI - Prostanoids inhibit release of endogenous norepinephrine from rat isolated trachea. AB - Prostanoids, of epithelial origin, are known as modulators of several processes in the airways. The present study examined whether prostanoids are involved in the local control of sympathetic neurotransmission. The release of endogenous norepinephrine from rat isolated tracheae was evoked by electrical field stimulation (3 Hz, 540 pulses) in the presence of yohimbine, desipramine, and tyrosine. In different series of experiments, indomethacin (3 mumol/L) increased the evoked release of endogenous norepinephrine by 70 to 80%. In the presence of indomethacin, prostaglandin E2 (PGE2) and several prostanoid receptor agonists inhibited the evoked release of norepinephrine in a concentration-dependent manner, maximally by 60 to 70%. According to the concentration producing 35% inhibition of norepinephrine release (half-maximal effect), the following rank order of potencies was observed (EC35): nocloprost (8 nmol/L), sulprostone (30 nmol/L), PGE2 (308 nmol/L), iloprost (2 mumol/L), and U46619 (> 10 mumol/L). The EP1 receptor antagonist AH 6809 (3 mumol/L) had no effect on the evoked norepinephrine release and did not affect the inhibitory effect of 1 mumol/L of sulprostone. In the absence of indomethacin, the inhibitory effect of PGE2 was similar to that observed in the presence of indomethacin. After removal of the epithelium, the evoked norepinephrine release was markedly reduced. However, no significant effect of indomethacin was observed in epithelium-denuded tracheae. In conclusion, norepinephrine release in the rat trachea is inhibited via prostaglandin receptors that have the pharmacologic characteristics of the EP3 subtype. Endogenous eicosanoids, most likely of epithelial origin, are involved in the local control of the release of norepinephrine. PMID- 1443868 TI - Angiotensin II-1 receptor-mediated Cl secretion by canine tracheal epithelium. AB - To elucidate the effect of angiotensin II (AII) on ion transport function of airway epithelium, we studied the bioelectrical properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. Addition of AII to submucosal solution in Ussing chambers increased the short-circuit current (ISC) in a dose-dependent fashion, the maximal increase from the baseline value and the concentration required to produce a half-maximal effect being 5.2 +/- 0.5 microA/cm2 (p < 0.001) and 10(-6) M, respectively. In contrast, mucosal AII had little effect. The AII-induced increase in ISC was not altered by the AII-2 receptor antagonist EXP655 but was depressed by the AII-1 receptor antagonist DuP 753. Diphenylamine-2-carboxylate, Cl-free medium, indomethacin, the phospholipase A2 inhibitor mepacrine, and the methyltransferase inhibitor 3-deazaadenosine reduced the change in ISC, whereas amiloride and the lipoxygenase inhibitor AA 861 did not. Addition of AII to the submucosal but not the mucosal side increased the release of prostaglandin E2, an effect that was abolished by DuP 753. These results suggest that AII may interact with the submucosal AII-1 receptor and stimulate Cl secretion across tracheal epithelium through the mobilization of arachidonic acid and the release of prostaglandin E2. PMID- 1443869 TI - Furosemide differentially relaxes airway and vascular smooth muscle in fetal, newborn, and adult guinea pigs. AB - Furosemide, an inhibitor of Cl-dependent Na+,K+ cotransport, is the most frequently used diuretic in newborns. Recently, furosemide was also demonstrated to decrease bronchial hyper-responsiveness in adults, although little is known about the direct effect of furosemide on smooth muscle of immature animals. This in vitro study was designed to determine the action of furosemide on airway and vascular smooth muscle during ontogeny. Extrathoracic trachea (ET), main stem bronchi, main pulmonary artery, and thoracic aorta ring segments from fetal, newborn, and adult Hartley albino guinea pigs were suspended in HEPES solution for measurement of isometric tension. Furosemide (30 or 300 microM) was administered after preconstriction with an ED35-70 concentration of histamine or acetylcholine for airway and ED40-100 concentration of norepinephrine for vessels. Furosemide (30 microM) caused significant relaxation of airway smooth muscle at all ages. After histamine-induced preconstriction, fetal airway segments exhibited greatest relaxation (183 +/- 28%), with newborn airway demonstrating 123 +/- 15% relaxation and modest relaxation seen in adults (40 +/- 4%). This pattern was similar for both ET and bronchus and appeared greater for histamine compared with ACh preconstriction. Epithelial removal slightly enhanced relaxation. Furosemide also relaxed pulmonary artery segments, but at a 10-fold higher concentration. In striking contrast to the pattern seen in airway, adult pulmonary artery relaxed more than newborn and newborn, more than fetus. Cyclooxygenase blockade and endothelium removal did not change pulmonary artery relaxation. Furosemide did not significantly relax aorta after NE preconstriction. Taken together, these results suggest that furosemide may be more effective in relaxing airway compared with vascular smooth muscle, and the ontogeny of these responses indicates a greater efficacy and selectivity in airways of immature animals. PMID- 1443870 TI - Effects of natriuretic peptides and neutral endopeptidase 24.11 inhibition in isolated perfused rat lung. AB - We have studied the acute effect of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) on pulmonary vascular tone in normoxia and acute hypoxia in the absence and presence of a specific inhibitor of neutral endopeptidase 24.11 (NEI, UK 73, 967, candoxatrilat; Pfizer) in the isolated and blood-perfused rat lung preparation. Baseline pulmonary artery pressure (Ppa) was 16.4 +/- 0.3 mm Hg in lungs from normoxic control rats and 22.5 +/- 0.3 mm Hg in lungs from rats kept in hypoxia (FIO2 = 10%) for 7 days. Acute hypoxic pulmonary vasoconstriction (HPV delta Ppa) was similar in normoxic control rats (9.5 +/- 0.6 mm Hg) and chronically hypoxic rats (9.8 +/- 0.9 mm Hg). NEI at 0.07 and 0.2 mg had no effect on baseline Ppa or HPV delta Ppa. Synthetic BNP at 10 nM had no effect on baseline Ppa but produced a 2.8 +/- 0.2 mm Hg reduction in HPV delta Ppa alone and 2.7 +/- 0.2 mm Hg reduction in the presence of 0.07 mg NEI in normoxic control rats. In contrast, ANP at 10 nM produced a significantly greater decrease in HPV delta Ppa in the presence of 0.07 mg NEI (4.8 +/- 0.3 mm Hg, p < 0.05) compared with ANP alone (2.9 +/- 0.4 mm Hg), and similar results were also observed in chronically hypoxic rats. Thus, BNP has a vasodilator effect similar to that of ANP in the pulmonary circulation. Inhibition of neutral endopeptidase 24.11 augments the effects of ANP on HPV but does not influence the pulmonary vascular responses to BNP. PMID- 1443871 TI - Effects of in utero phrenic nerve section on the development of collagen and elastin in lamb lungs. AB - Interference with fetal breathing movements is known to retard morphologic development of the lung and to reduce compliance. We hypothesized that the lower compliance might be in part due to effects on lung structural proteins. We studied the effects of phrenic nerve section in utero on lung compliance and on the lung contents of collagen, elastin, and DNA. At 110 to 112 days of gestation, one fetal lamb in each of 12 twin pregnancies had either both phrenic nerves cut (PX) or a sham operation (S). The other twin was left unoperated (Upx, Us) as a control. They were killed 14 to 22 days later, and the concentrations in lung parenchyma of collagen (as hydroxyproline HPro), elastin, and DNA were measured, together with lung compliance and dry and wet weight. Paired comparisons were made (PX versus Upx and S versus Us). Both operated groups (PX, S) had smaller lungs with lower water content than did their unoperated twins. Absolute static compliance in PX was reduced, but compliance relative to lung weight was unchanged, and there was no significant difference between S and Us. There were no significant effects of PX on the concentrations of HPro, elastin, and DNA, or on the elastin/collagen ratio. Compliance was not correlated with either HPro or elastin content. HPro content increased significantly with gestational age in all groups. It is concluded that phrenic nerve section retards the increase of lung compliance and possibly air space, but it does not affect the overall rate of lung cell proliferation or of deposition of elastin or collagen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443872 TI - Ventilation and gaseous metabolism in infants born at high altitude, and their responses to hyperoxia. AB - Hyperventilation and decreased metabolic rate are commonly observed in newborns during acute hypoxia; whether these responses are also present during sustained hypoxia is not known. We asked whether infants at high altitude had higher ventilation and lower metabolism than lowlanders. Ventilation (VE), oxygen consumption (VO2), and carbon dioxide production (VCO2) were measured in newborn (< 1 day old) full-term infants in La Paz (altitude 3,800 m; inspired oxygen pressure [PIO2], 92 mm Hg) and in Santa Cruz (altitude, 400 m; PIO2, 141 mm Hg), Bolivia. Each group consisted of 30 infants selected to have similar body weight. The mothers, Amerindians and mestizos, were born in the corresponding cities or at equivalent altitudes. Despite the lower inspired oxygen concentration in La Paz (0.107 ml STPD O2/ml BTPS air) than in Santa Cruz (0.164), neither VE nor VO2 or VCO2 differed between the two groups. The breathing pattern was deeper and slower at high altitude. From the values of VE and VO2 it was calculated that high-altitude infants extracted more O2 (+62%) from the inspired air than did the lowlanders. When given pure O2 to breathe, both groups of infants similarly increased VE and gaseous metabolism; even during hyperoxia, however, the ventilatory O2 extraction was higher (+50%) in the highlanders. We conclude that, contrary to what is observed in acute hypoxia, infants at high altitude maintain metabolic rate with no major alterations in VE. The ability to use a greater fraction of the inspired O2 at high altitude probably results from functional and structural alterations stimulated by fetal hypoxia. PMID- 1443873 TI - Characterization of gamma/delta T-lymphocytes in the peripheral blood of patients with active tuberculosis. A comparison with normal subjects and patients with sarcoidosis. AB - Studies in experimental animals have suggested that gamma/delta T-cells play an important role in the immune response against mycobacteria, but evidence for the participation of these cells in the course of human tuberculosis remains fragmentary. We have evaluated the number and state of activation of gamma/delta T-cells in the peripheral blood of patients with active tuberculosis using two color cytofluorometry, and we have sought evidence that these cells might play a role in the impaired responses to recall antigens seen in some patients by comparing the proliferation of blood T-lymphocytes before and after removing gamma/delta T-cells by panning. Results were compared with those obtained for cells from normal subjects and from patients with sarcoidosis. The proportion and absolute number of circulating CD3+ gamma/delta T-cells were not significantly different comparing blood from patients with tuberculosis and that from control subjects [54.6 +/- 39.9 (n = 17) and 59.1 +/- 30.2 cells/microliters (n = 10), respectively, p > 0.2], and the proportion of cells expressing receptors using the V delta 1 variable region remained unchanged in patients with tuberculosis. Few gamma/delta T-cells from patients with tuberculosis expressed surface antigens associated with activation (IL-2R, < 1%; HLA-DR, 2.6 +/- 3.4%). Four of 15 patients with sarcoidosis had a proportion of gamma/delta T-cells that was outside the range observed in normal subjects, but the absolute number of CD3+ gamma/delta T-lymphocytes was not different comparing the two groups (p > 0.2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443874 TI - Dissociation between dyspnea and respiratory effort. AB - Breathlessness induced by hypercapnia may be related to the sensation of respiratory effort or to the central or peripheral effects of CO2. To examine the relationship among breathlessness, respiratory effort, and hypercapnia, we studied eight normal naive subjects. By using a visual feedback system, subjects maintained a constant ventilation of 50-60 L/min. PETCO2 was held at 40 mm Hg during the first 2 min of each trial (control period), then for 4 min (test period) was either kept at 40 mm Hg or elevated to 50 mm Hg. At the end of each control and test period, subjects were asked to give separate ratings for dyspnea (an unpleasant urge to breathe) and for the sense of respiratory effort (analogous to lifting a weight) on a 50-cm visual analog scale. Hypercapnia was associated with a significant reduction in effort ratings (-7.3 +/- 6.4, mean +/- SD, p < 0.05) and a concomitant increase in dyspnea (+6.6 +/- 6.0, p < 0.05). We conclude that dyspnea associated with hypercapnia is dissociated from changes in respiratory effort, and that CO2 has a direct central effect that leads to breathlessness. Our data also suggest that the sense of effort at a given level of ventilation is less when the ventilation is the result of "reflex" stimuli to breathe rather than "voluntary" signals to the respiratory muscles. PMID- 1443875 TI - Evidence of acute diaphragmatic fatigue in a "natural" condition. The diaphragm during labor. AB - Acute diaphragmatic fatigue has been experimentally shown to occur in normal healthy subjects and in patients with chronic obstructive pulmonary disease by asking them to modify their pattern of breathing or to breathe against high inspiratory resistances. During the expulsive period of labor women are asked periodically to make strong expulsive efforts and to sustain them isometrically for many seconds; this is likely to produce "natural" diaphragmatic fatigue. To investigate whether this was the case, six women were studied in the delivery room from the moment of the rupture of the amnion until delivery of the infant occurred. The development of diaphragmatic fatigue was assessed both by measuring the static maximal inspiratory pressure (MIP) and by analyzing the electromyographic power spectrum of the diaphragm (H/L ratio). The majority of contractions were concentrated in the expulsive period of labor. MIP, recorded in the supine position, significantly decreased from 103.2 +/- 17.2 cm H2O (at the beginning of the expulsive period) to 73.8 +/- 10.1 cm H2O (after the delivery). The H/L ratio fell progressively during the expulsive period; after the delivery, it was 59.2 +/- 15.7% of the value recorded at the beginning of the expulsive period. This study demonstrates that (1) the diaphragm is active in the expulsive efforts during labor and (2) the tension developed and the time each contraction is maintained may lead to the development of diaphragmatic fatigue. Therefore, we provide evidence of acute diaphragmatic fatigue in a natural condition. PMID- 1443876 TI - Adult criteria for obstructive sleep apnea do not identify children with serious obstruction. AB - Although obstructive sleep apnea (OSA) occurs in the pediatric population, diagnostic criteria have not been established. Since criteria for adult OSA are well established, we asked whether commonly used adult criteria, such as the apnea index (based on the number of obstructive apnea [OA] events per hour), would identify children with serious sleep-related upper airway obstruction. Polysomnographic data were analyzed from 20 children (ages 8 months to 16 yr) with clinical evidence of upper airway obstruction during sleep (loud snoring and labored breathing) and who had cyclic oscillations of oxyhemoglobin saturation (SaO2) during sleep. The overnight studies included sleep state (EEG, EOG, and EMG), SaO2, ECG, nasal (end-tidal CO2) and oral (thermistor) airflow, chest and abdominal movement (inductance plethysmography), and video camera and behavioral observations. Measurements included the number of obstructive events > or = 10 s, the number of desaturations (> or = 5% decrease lasting > or = 5 s), the number of desaturation episodes to < 90%, < 85%, and < 80% lasting > 5 s, and the percentage of sleep time with SaO2 values < 90%. Gas exchange was impaired as evidenced by cyclic decreases in SaO2 and elevated PETCO2 values (maximum value 58 +/- 6 mm Hg). The children experienced 175 +/- 168 (range 6 to 609) episodes of decreased SaO2 > 5%, with an average minimum SaO2 of 66 +/- 13% (range 30 to 85%). The average number of apnea events was only 1.9 +/- 3.2 events/h (range 0 to 10.4).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443877 TI - Normal polysomnographic values for children and adolescents. AB - Although polysomnography is routinely performed to evaluate children and adolescents with sleep-disordered breathing, normal polysomnographic values for the pediatric age group have not yet been established. We therefore performed overnight polysomnography in 50 normal children and adolescents (mean age 9.7 +/- 4.6 SD yr, range 1.1 to 17.4 yr). Of the children 56% were male. Chest wall motion, ECG, oronasal airflow, end-tidal PCO2 (PETCO2), arterial oxygen saturation (SaO2), and electrooculogram were monitored. Children had 0.1 +/- 0.5 (range 0 to 3.1) obstructive apneas per hour of total sleep time, with only 18% of children having any obstructive apneas. No child had obstructive apneas > 10 s in duration. Of the children 30% had central apneas > or = 10 s in duration, and one child had a central apnea associated with SaO2 < 90%. Peak PETCO2 was 46 +/- 4 mm Hg (range 38 to 53 mm Hg), and hypoventilation (PETCO2 > 45 mm Hg) occurred for 7 +/- 19% total sleep time (range 0 to 91%). The SaO2 nadir was 96 +/- 2% (range 89 to 98%), with only one child desaturating below 90% in association with a central apnea. We conclude that polysomnographic results in the pediatric age group differ from those in adults. Recommendations for normal polysomnographic criteria are given. PMID- 1443878 TI - A specific and potent pressor effect of hypoxia in patients with sleep apnea. AB - A hypoxic ramp test (to 75% arterial oxygen saturation) during the awake state was performed in 17 patients with obstructive sleep apnea (OSA). Blood pressure was monitored with an indwelling arterial line (radial artery), and the ventilatory response to eucapnic hypoxia was determined. Eight of the patients were normotensive. The remaining nine hypertensive patients were studied after a 3-wk washout of antihypertensive medication. Compared with a nonmatched group of normotensive nonsnoring control subjects in whom hypoxemia did not affect blood pressure, all OSA patients showed various degrees of pressor responses during hypoxia. The pressor response was of similar magnitude in normotensive and hypertensive patients with OSA. There was a significant relationship between the ventilatory and the pressor responses to hypoxia (p = 0.03) that was similar in both normotensive and hypertensive patients. Although disease severity expressed as apnea index (number of apneas per hour of sleep) or minimum arterial oxygen saturation reached during the overnight recording correlated with the magnitude of the pressor response (p = 0.03 and 0.045, respectively), the ventilatory response to hypoxia was unrelated to disease severity. Hypoxemia induced a similar increase in heart rate in controls and in normotensive patients, but an attenuated heart rate response was seen at the nadir of oxygen saturation in hypertensive subjects (p < 0.05). These data demonstrate that patients with obstructive sleep apneas have a pressor response to hypoxia. This response is likely to be involved in the blood pressure swings seen during apnea in patients with OSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443879 TI - Temperature thresholds in the oropharynx of patients with obstructive sleep apnea syndrome. AB - The temperature thresholds for warmth and cold were determined on the oropharyngeal mucosa of 15 patients with obstructive sleep apnea syndrome (OSAS) and 15 age-matched nonsnoring control subjects. We found that six of the patients with OSAS were not able to detect either the upper (50 degrees C) or lower (25 degrees C) temperature limits of the test when recording from the tonsillar pillar, whereas all control subjects detected the temperature change within the measuring range. The OSAS patients showed a statistically significant higher threshold for warmth on the anterior tonsillar pillar, 46.8 degrees C (95% confidence interval 45.2-48.4) versus 42.5 degrees C (41.3-43.8) for the control subjects (p = 0.0006). The same was found on the tip of the tongue-40.1 degrees C (38.7-41.6) for OSAS patients and 38.2 degrees C (37.1-39.4) for the control subjects (p = 0.036). Determination of temperature thresholds on the skin is an established method of detecting a neuropathy. We speculate that patients with OSAS suffer from a neuropathy in the pharynx caused by prolonged and progressive trauma to the pharyngeal structures from vibration induced by snoring and/or stretching of the structures during apneas. A neuropathy may interfere with the normal stabilizing function of the pharyngeal muscles and with the local reflex mechanism preventing the upper airway from collapsing during inspiration. It is thus possible that snoring itself, by inducing a neuropathy in the pharynx, may contribute to the sequence of events that transform a snorer into a patient suffering from OSAS. PMID- 1443880 TI - Respiratory short-term poststimulus potentiation (after-discharge) in patients with obstructive sleep apnea. AB - In conscious normal humans after a brief hypoxic ventilatory stimulus, ventilation slowly decays to baseline and does not undershoot though the subjects are hyperoxic and hypocapnic. This phenomenon is attributed to short-term poststimulus potentiation (STP), which may be an important factor promoting ventilatory stability by preventing periodic breathing. It has been proposed that obstructive sleep apnea (OSA) is a variant of periodic breathing, with obstruction occurring when ventilatory drive is low. If this were the case, patients with OSA might have reduced STP. To test this, seven normal adults and 12 patients with OSA (mean apnea index, 52.4 +/- 6.9 SE events/h) were studied. Ventilation (VI) was measured in awake seated subjects during 30 to 45 s of exposure to hypoxia (end-tidal O2: 50 mm Hg) followed by hyperoxia. A total of 57 hypoxic-hyperoxic runs were analyzed (36 in the patients and 21 in the normal subjects). During hypoxia VI increased and end-tidal CO2 decreased by similar amounts in both groups. In normal subjects after hypoxia there was a gradual decay in VI to prehypoxic levels without an undershoot. In patients, there was on average a ventilatory undershoot at 35 s of hyperoxia, with a mean VI of 83% of baseline. The undershoot was due mainly to a decrease in tidal volume, which was significantly lower than that of the normal subjects for several seconds. These changes were particularly prominent in seven patients who were not different from the others in terms of baseline characteristics, hypoxic responses, and OSA severity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443881 TI - The effect of triazolam on the arousal response to airway occlusion during sleep in normal subjects. AB - The purpose of this study was to assess the effect of triazolam (0.25 mg) on the arousal response to airway occlusion during nonrapid eye movement sleep in normal subjects. Six male subjects (mean age +/- SD, 28.1 +/- 7.1 yr) had their arousal response tested by occluding a mask covering the nose with the mouth sealed. After an adaptation night, subjects were studied on two consecutive nights. They ingested triazolam (0.25 mg) or placebo one-half hour before bedtime in a randomized double-blind crossover manner. Mask occlusion was performed 1 to 4 h after triazolam/placebo ingestion while the subjects breathed a mixture of air and oxygen adjusted to produce an arterial oxygen saturation of 98%. The maximal deflections in airway pressure were measured at a supraglottic location during airway occlusion to reflect the degree of inspiratory effort. The time to arousal (mean +/- SEM) was significantly longer on triazolam nights (32.0 +/- 5.2 versus 22.6 +/- 3.2 s, p < 0.01). The maximal airway suction pressure preceding arousal was higher on triazolam nights (26.5 +/- 2.0 cm H2O versus 20.0 +/- 1.2 cm H2O, p < 0.02). Conversely, the rate of increase in inspiratory effort (maximal pressure) during occlusion was not decreased by triazolam. We conclude that triazolam prolongs the time to arousal following airway occlusion by increasing the arousal threshold. PMID- 1443882 TI - Effects of surgical correction of nasal obstruction in the treatment of obstructive sleep apnea. AB - Negative upper airway pressure is thought to play a key role in the pathophysiology of obstructive sleep apnea. Because nasal resistance contributes to the increase of the transpharyngeal pressure gradient, we evaluated the effects of nasal surgery on sleep-related breathing abnormalities in 20 adults with obstructive sleep apnea. Polysomnographic studies were done before (baseline), and 2 to 3 mo after surgery (septoplasty, turbinectomy, and/or polypectomy). Nasal resistances were measured at these visits in 14 patients. Cephalometric measurements were obtained before surgery. Cephalometric abnormalities consisted in an increase in the distance from the mandibular plane to the hyoid bone (MP-H), a decrease in the space between the base of the tongue and the posterior soft tissues (PAS), a retroposition of the mandibule, and an increase in the length of the soft palate. Body weight did not change between the two studies. Nasal resistance decreased significantly after nasal surgery. The composition of the total sleep time spent in the rapid eye movement stage increased from 11.5 +/- 1.3% (mean +/- SEM) to 14 +/- 1.2% after surgery. For the group as the whole, there was no difference between baseline and postsurgical values in the frequency of respiratory disturbances (39.8 +/- 6.1, 36.8 +/- 5.9 n/h), the total apnea time (17.8 +/- 4.2, 15.4 +/- 2.8), the distribution of the apnea time within the different apnea types (obstructive and nonobstructive), and the severity of the nocturnal desaturations. Interestingly, apnea and apnea plus hypopnea indices returned to normal values (< 5 and 10, respectively) in four subjects with normal posterior soft tissues and mandibular plane to the hyoid bone distances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443883 TI - Fiber type and regional differences in oxidative capacity and glycogen content in the hamster diaphragm. AB - The purpose of this study was to define variability of the oxidative capacity and glycogen content between different fiber types and regions of the hamster diaphragm. Using histochemical and microphotometric techniques, the oxidative capacity (identified by nicotinamide-adenine dinucleotide tetrazolium reductase reaction end product) and glycogen levels (identified by the periodic acid-Schiff stain test) were examined in three myofibrillar ATPase (M-ATPase) fiber types and four diaphragmatic regions: sternal, anterior costal, thoracic surface of the crural (thor/crur), and abdominal surface of the crural (abd/crur). Most regional differences were found between the crus and the rest of the diaphragm. There were no differences in the oxidative capacity between diaphragmatic regions in the types 1 and 2a fibers, but the type 2b fibers in the thor/crur region had the greatest oxidative capacity and the 2b fiber in the sternal region had the lowest oxidative capacity. There were differences in glycogen content between diaphragmatic regions for all of the three M-ATPase fiber types. Variability in oxidative capacity between fiber types was demonstrated in all regions except the thor/crur region. Variation in glycogen content between fiber types was only demonstrated in the two surfaces of the crus. The type 2b fiber demonstrated the most differences from types 1 and 2a fibers in oxidative capacity and glycogen content in the different diaphragmatic regions, whereas the types 1 and 2a fibers demonstrated few differences from each other in these features across the different diaphragmatic regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443884 TI - Lung oxidant changes after zymosan peritonitis: relationship between physiologic and biochemical changes. AB - Our purpose was to determine the effect of non-bacteria-dependent systemic inflammation on the degree and time course of lung oxidant activity and antioxidant defenses, comparing these changes with lung, physiologic, and histologic alterations. Adult male rats were given intraperitoneal zymosan (0.7 mg/g body weight) and were fluid resuscitated. Oxidant changes were measured as lung tissue oxidized glutathione (GSSG) and malondialdehyde (MDA) content, antioxidant defenses as tissue reduced glutathione (GSH), and catalase. Animals were killed at 4, 12, and 24 h, and at 5, 10, and 30 days. Lung data were compared with that found in liver. We noted a 45% mortality in the first 18 to 36 h with all remaining animals surviving. In the first 24 h, we noted a doubling of lung MDA and an 80% conversion of tissue GSH to GSSG compared with less than 5% in control animals, indicating a severe oxidant stress. These findings corresponded with marked increase in lung neutrophils. Arterial pressure (PaO2) was significantly decreased from a control of 95 +/- 4 mm Hg to 80 +/- 5 mm Hg and 75 +/- 4 mm Hg at Days 5 and 10, respectively, but returned toward control by 30 days. Lung GSSG and MDA remained significantly increased for the 30-day period, whereas amounts of the antioxidants, catalase, and GSH returned to control after 24 h. The ongoing oxidant stress corresponded with marked mononuclear cell infiltration and interstitial thickening, which persisted over the 30-day period even after peritonitis had completely resolved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443885 TI - The effect of aerosolized recombinant human granulocyte macrophage colony stimulating factor on lung leukocytes in nonhuman primates. AB - The number and function of myeloid cells in the lungs are critical determinants of health and disease. To examine whether these cells can be modulated in vivo by a colony-stimulating factor (CSF), recombinant human granulocyte macrophage-CSF (GM-CSF) was given to cynomolgus monkeys by either continuous intravenous infusion (7,200 U/kg/day) for 2 wk or by aerosol exposure to 10(7) U on 1 or 2 consecutive days. At intervals after the initiation of GM-CSF administration, animals underwent bronchoalveolar lavage (BAL) and had peripheral blood sampled to characterize changes in lung and circulating phagocytic cells. Compared with animals exposed to bovine serum albumin, there was an increase in the total number of BAL cells retrieved. This increase was greatest in animals receiving aerosolized GM-CSF, and it was the result of more macrophages and neutrophils. Both lung macrophages and blood neutrophils from animals exposed to aerosolized GM-CSF exhibited an augmented respiratory burst in response to phorbol myristate acetate. Lung macrophages from GM-CSF-exposed animals exhibited increased capacity to bind and/or ingest opsonized and unopsonized Staphylococcus aureus. Despite functional activation of lung phagocytic cells, biochemical analyses of BAL fluid for markers of lung injury revealed an increase in only some parameters in the GM-CSF group. Intravenous administration of GM-CSF had the expected effect on augmenting the number of myeloid cells in the bloodstream. Aerosolized GM-CSF produced a transient effect on circulating myeloid cell number between 3 and 5 days after exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443886 TI - Hyperoxia-induced airway remodeling in immature rats. Correlation with airway responsiveness. AB - We recently found that exposure of 21-day-old rats to hyperoxia (> 95% O2 for 8 days) significantly increased in vivo airway cholinergic responsiveness and that O2 exposure also increased airway epithelial and smooth muscle layer thicknesses in a separate cohort of animals. There was substantial variation in the magnitude of both the functional and structural responses to hyperoxia. The present study was designed to test whether the magnitude of O2-induced airway remodeling could account for individual differences in airway responsiveness after O2 exposure, as well as for the difference in responsiveness between air- and O2-exposed animals. We assessed in vivo airway responsiveness to aerosolized acetylcholine (ACh) and airway architecture in 14 O2- and 5 air-exposed, immature rats. Total respiratory system resistance was determined using a plethysmographic method. The mean thicknesses and fractional areas of the airway epithelial and smooth muscle layers were determined by contour tracing using a digitizing pad and microcomputer. Both the small (circumference < 1,000 microns) and central (circumference 1,000 to 4,000 microns) airways were studied. For O2-exposed rats, individual values of EC200 ACh correlated negatively with small airway smooth muscle layer thickness (r = -0.59, p < 0.05; ANOVA), small airway smooth muscle layer fractional area (r = -0.75, p < 0.01), small airway epithelial thickness (r = -0.54, p < 0.05), small airway epithelial fractional area (r = -0.69, p < 0.01), and central airway smooth muscle layer thickness (r = -0.53, p < 0.05). When both air- and O2-exposed animals were considered, EC200 ACh correlated negatively with all eight parameters of airway layer thickness and fractional area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443887 TI - Bradykinin causes airway hyperresponsiveness and enhances maximal airway narrowing. Role of microvascular leakage and airway edema. AB - The relationship between bronchial edema and airway responsiveness was studied in cats in situ. Five cats were exsanguinated, and the bronchial arteries were perfused. We monitored pulmonary resistance (RL), and the provocative dose of acetylcholine (ACh) required to produce a 300% increase in RL (PD300) was determined. Bronchial vascular permeability was measured by quantifying extravasation of Evans blue (EB) dye. Bradykinin (BK) and ACh were administered via the bronchial arteries to increase leakage and bronchoconstriction, respectively. BK preperfusion (for 30 min) significantly increased bronchial vascular permeability to four times the control values (p < 0.05). BK preperfusion did not alter baseline RL but caused hyperresponsiveness to ACh, with log [PD300 (mole)] of -6.53 +/- 0.42 (mean +/- SD) and -6.90 +/- 0.30, before and after BK, respectively (p < 0.01). Furthermore, the maximal airway narrowing after BK was 58% higher than before BK (p < 0.01). Histologic study showed peribronchial edema after BK. The enhancement of maximal airway narrowing was significantly correlated with the degree of EB dye extravasation. These results suggest that BK causes airway hyperresponsiveness to ACh and increases maximal airway narrowing, possibly because of airway edema. PMID- 1443888 TI - Bronchoconstriction and airway microvascular leakage in guinea pigs sensitized with trimellitic anhydride. AB - We have developed a guinea pig model of immediate airway responses following intradermal sensitization with free trimellitic anhydride (TMA). Guinea pigs were given an intradermal injection with either 0.1 ml of 0.3% TMA in corn oil (n = 8) or 0.1 ml of corn oil alone (n = 6). A guinea pig serum albumin conjugate of trimellitic anhydride (TMA-GPSA) was prepared with a substitution ratio of 21:1. All sensitized guinea pigs had raised specific serum IgG1 antibodies (ELISA), and IgE antibodies were detected in six of the eight sensitized guinea pigs by passive cutaneous anaphylaxis. On Days 21 to 28, guinea pigs were anesthetized, tracheostomized, and ventilated. Evans blue dye (20 mg/ml), an albumin marker, was injected intravenously to quantify airway microvascular leakage (MVL). TMA GPSA (50 microliters; 1%) in saline was instilled into the trachea. Lung resistance (RL) was measured for 6 min. The guinea pigs were killed, and the lungs were removed. Peak RL (cm H2O/ml x s-1) was significantly increased in sensitized guinea pigs from 0.26 +/- 0.01, mean +/- SEM to 21.3 +/- 6.9 (p < 0.05), compared with nonsensitized guinea pigs. There was a significant increase in Evans blue at all levels of the tracheobronchial tree in sensitized guinea pigs compared with the controls (p < 0.005). The site of MVL was localized to the postcapillary venules as assessed by extravasation of intravascular Monastral blue dye. We conclude that intradermal sensitization of guinea pigs to TMA induces a polyclonal immune response, associated with bronchoconstriction and airway microvascular leakage, when challenged specifically with TMA GPSA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443889 TI - Bronchial hyperreactivity after inhalation of trimellitic anhydride dust in guinea pigs after intradermal sensitization to the free hapten. AB - We have developed in the guinea pig, an animal model of bronchial hyperreactivity provoked by inhalation of trimellitic anhydride (TMA) dust, a known cause of occupational asthma in humans, after intradermal sensitization to the free hapten. Male Dunkin-Hartley guinea pigs (n = 6) were injected intradermally with 0.1 ml of 30% TMA in corn oil. Control animals (n = 7) were injected with 0.1 ml corn oil alone. On Days 21 to 28 after sensitization, guinea pigs were challenged (nose only) to 12 mg/m3 of inhalable TMA dust for 30 min. Bronchial reactivity was measured in sensitized animals and in control animals at 8 h after exposure to the dust. We also measured bronchial reactivity in sensitized exposed guinea pigs at 2 h (n = 5) and at 24 h (n = 5). Pulmonary inflation pressure (PIP) was used to assess bronchopulmonary response. Blood samples were taken for assessment of IgG-1 antibodies to TMA conjugated to guinea-pig albumin. The concentration of acetylcholine required to induce a 100% increase in PIP was used to assess bronchial reactivity. The lungs were eviscerated for histologic examination. All guinea pigs injected intradermally with TMA had high titers of specific IgG-1 antibodies to TMA conjugated to guinea-pig albumin. There was a significant increase in bronchial reactivity in sensitized guinea pigs 8 h after exposure to the TMA dust compared with that in the control animals. There was also a significant eosinophilic inflammatory influx in the subepithelium of the sensitized groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443890 TI - Relationship among mediators, inflammation, and volume history with antigen versus hyperpnea challenge in guinea pigs. AB - Paralyzed mechanically ventilated guinea pigs constricted to a similar degree by either isocapnic hyperpnea or antigen challenge display significantly different lung resistance (RL) volume history responses to a deep breath. We compared bronchoalveolar lavage (BAL) mediator profiles, BAL total protein concentrations, and tissue histopathology of antigen-constricted (AC), hyperpnea-constricted (HC), and control guinea pigs to determine whether patterns of volume history near peak constriction could be related to specific patterns of lung mediators, indices of microvascular leakage, or severity of tissue inflammation assessed pathologically. Methacholine constricted (MC) animals served as a second control group for assessing the effects of direct smooth-muscle contraction on indices of inflammation and volume history responses. Our results show that despite similar baseline and postchallenge RL, HC and MC animals displayed significant constriction reversal after a deep lung inflation, whereas AC animals did not. BAL concentrations of prostaglandin D2(PGD2), thromboxane B2 (TxB2), and leukotriene C4/D4/E4 (slow reacting substance of anaphylaxis, SRSA) were significantly elevated in both AC and HC animals compared with control and MC animals, with AC and HC BAL differing only with respect to PGD2 values (AC 2.4 fold higher). BAL total protein in AC animals was significantly greater than in HC, MC, and control animals. Histopathology showed significant peribronchial and interstitial cellular inflammation in AC animal specimens, whereas specimens from HC animals had little or no inflammation. Differences in volume history responses observed between equally constricted AC, HC, and MC animals may be due to differences in airway and/or parenchymal microvascular leak and cellular inflammation. PMID- 1443891 TI - Increased expression of endothelin in bronchial epithelial cells of asthmatic patients and effect of corticosteroids. AB - We have previously demonstrated that human bronchial smooth muscle cells possess specific binding sites for the potent bronchoconstrictive peptide endothelin 1 and that primary cultures of human bronchial epithelial cells constitutively produce an endothelin-like material that binds to smooth muscle cell receptors with a kinetic ability analogous to that shown by the authentic peptide. To evaluate the potential role of airway epithelium-derived endothelin in the pathogenesis of asthma, we have examined here the expression of endothelin in the bronchial epithelial cells of 6 patients with symptomatic asthma and reversible airflow obstruction. The epithelial cells of 5 normal volunteers and 5 patients with chronic bronchitis and airflow obstruction unaffected by bronchodilators were tested as controls. The bronchial epithelial cells of all the asthmatic patients expressed preproendothelin 1 mRNA, as assessed by in situ hybridization, and released high amounts of mature and biologically active endothelin during a 48-h period of incubation (radioimmunoassay). By contrast, the epithelial cells from normal donors did not contain preproendothelin 1 transcripts, and the endothelin-like material in their supernatants was invariably below the detection limit of the assay. Only a few cells from 2 patients with chronic bronchitis expressed preproendothelin mRNA and endothelin immunoreactivity. When hydrocortisone (10(-6)M) was added to the culture medium of asthmatic bronchial epithelial cells for 48 h, the release of immunoreactive endothelin significantly decreased (p < 0.025), but the numbers of cells expressing preproendothelin 1 mRNA did not change to the same extent. PMID- 1443892 TI - Miliary Mycobacterium bovis induced by intravesical bacille Calmette-Guerin immunotherapy. AB - Intravesical instillation of bacille Calmette-Guerin (BCG), an attenuated strain of Mycobacterium bovis, is the treatment of choice for many patients with bladder cancer. In a small percentage, this therapy is associated with systemic side effects including pneumonitis. It is uncertain whether these systemic manifestations are due to dissemination of infection or due to hypersensitivity, an etiologic distinction that has important therapeutic implications. We report the first case in which miliary M. bovis was proven to be the responsible mechanism, by culture of M. bovis biovar BCG from a transbronchial lung biopsy and complete resolution on anti-tuberculous chemotherapy. PMID- 1443893 TI - Emphysema: the first two centuries--and beyond. A historical overview, with suggestions for future research: Part 1. PMID- 1443895 TI - Reporting the reproducibility of spirometry results. PMID- 1443894 TI - Effects of cigarette smoking on rate of loss of pulmonary function in adults: a longitudinal assessment. AB - Data from a random sample of 8,191 men and women selected in six U.S. cities and examined on three occasions over a 6-yr follow-up period were analyzed by longitudinal methods to describe the effects of smoking history and current smoking behavior on rate of loss of pulmonary function during adult life. Former smokers had age- and height-adjusted rates of decline (34.3 ml/yr for men and 29.6 ml/yr for women) comparable with those of never smokers (37.8 ml/yr for men and 29.0 ml/yr for women) but much smaller than those of continuing smokers (52.9 ml/yr for men and 38.0 ml/yr for women). The accelerated rate of loss of FEV1 among smokers depended linearly on the number of cigarettes smoked per day during the interval between examinations. The estimated increase in rate of loss associated with smoking was 12.6 ml/yr per pack/day for men and 7.2 ml/yr per pack/day for women. These longitudinal estimates of the effects of smoking were approximately 50% larger than estimates obtained from cross-sectional analysis of the initial pulmonary function examination. Men who started smoking had accelerated rates of loss (55.9 ml/yr) as did women (43.1 ml/yr). Smokers who stopped smoking between examinations had reduced declines (41.2 ml/yr for men and 28.7 ml/yr for women) compared with continuing smokers. The age-specific rates of loss suggest that the benefits of cessation may be greatest among the youngest smokers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1443896 TI - Pseudomonas adherence to rat tracheal epithelium. PMID- 1443897 TI - Lung function testing: selection of reference values and interpretative strategies. PMID- 1443898 TI - Adrenergic and cholinergic regulation of bronchial vascular tone. AB - The autonomic nervous system plays a vital role in the regulation of vasomotor tone. Previous studies of systemic arteries and veins have shown that the classic autonomic neurotransmitters, norepinephrine and acetylcholine, act on smooth muscle, adrenergic nerve endings, and endothelial cells in the blood vessel wall to regulate vasomotor tone. Similar studies with isolated tissues indicate that bronchial arteries are innervated by adrenergic neurons and that norepinephrine activates postjunctional alpha 1-adrenoceptors to cause smooth muscle contraction. Isolated canine bronchial arteries fail to relax in response to beta adrenoceptor agonists, and they do not contract when exposed to acetylcholine. This lack of responsiveness may be species-specific, however, since isolated bronchial arteries from other species respond to these agonists. Acetylcholine causes endothelium-dependent relaxation of bronchial arteries in vitro; this response is mediated by endothelial M3-muscarinic receptors. The role of the endothelium in mediating responses to adrenergic agonists, as well as the prejunctional effects of norepinephrine and acetylcholine on adrenergic nerve endings, remain to be explored in isolated bronchial arteries. PMID- 1443899 TI - Lymph and blood flow responses in central airways. AB - The lymphatic drainage of the lung has been used as a quantitation of pulmonary microvascular fluid flux in normal animals and after various forms of injury. This review supports the importance of the bronchial microvasculature in the formation of lung lymph. Proof that the lymph drainage of the lung comes from the pulmonary circuit has been based on the finding of an elevation of lymph flow when the pulmonary venous pressure is elevated. This proof is wanting since recent work demonstrates that the venous drainage of the intrapulmonary bronchi flows into the pulmonary vascular system at the precapillary level. The administration of endotoxin induces an elevation of lung lymph. The bronchial circuit may play a role in this response since it is likewise exposed to the high pulmonary pressures induced by endotoxin, and there is evidence that ischemia/reperfusion injury to the airway occurs with endotoxin administration. After acute lung injury from smoke inhalation, lung lymph flow is markedly elevated. The lymph drainage from the airway may play an important role in this response. Bronchial blood flow is markedly increased after inhalation injury and there is airway edema. The increases in lung lymph flow and extravascular lung water are markedly reduced by occlusion of the bronchial artery. These data support the need for additional study of the role of the bronchial circulation in the formation of lung lymph. PMID- 1443900 TI - Effect of airway blood flow on airflow. AB - Resistance to gas flow of an airway is a function of both airway smooth muscle tone and thickness of the airway wall internal to the outer ring of airway smooth muscle. Schematically, the increase in airway resistance caused by shortening of airway smooth muscle may be potentiated by a concomitant increase in airway wall thickness caused by vasodilation of the bronchial vessels and/or microvascular leakage. Conversely, bronchial vasoconstriction may limit to some extent the increase in resistance to gas flow caused by airway smooth muscle shortening and/or congestion and edema of the airway wall. Many endogenous paracrine mediators, putatively involved in asthma and bronchial hyperresponsiveness, have both bronchomotor and vascular effects. The overall effects on resistance to airflow of endogenous or exogenous agents depend not only upon pre-existing airway smooth muscle tone and pre-existing condition of bronchial vessels but also upon two factors that facilitate microvascular leakage, namely, inflammation of the airway wall and outflow pressure of the bronchial circulation, which is close to left atrial pressure. PMID- 1443901 TI - Microvascular function. Transvascular exchange of fluid in the airways. AB - Fluid exchange in the airway microcirculation is presented relative to whether the airway epithelium is in an absorbing or a secreting state. The effects of increasing microvascular pressures and damaging the endothelial barrier are also examined relative to fluid dynamics and lymph flow, especially with regard to "filtration secretion." The microvessel pressure profile of the tracheal circulation is discussed relative to our recent data and to the published literature. These micropuncture data indicate that the major resistance to tracheal blood flow resides in arterioles with diameters less than 50 microns. It is hoped that this review will stimulate research on the airway microcirculation since the available data on the physiology and biophysics of circulation in the large and small airways are insufficient to define the microcirculatory exchange characteristics in this capillary bed. PMID- 1443902 TI - Cellular and intercellular transport pathways in exchange vessels. AB - The endothelium of lung alveolar capillaries is of the continuous type, that of airway exchange vessels (capillaries and pericytic venules) includes both continuous and fenestrated types. Water and small lipophilic solutes penetrate via the endothelial cells (cell membrane pathway) as well as through intercellular junctions. Hydrophilic solutes are limited to junctional pathways and cytoplasmic vesicles. Permeation of hydrophilic solutes is progressively restricted with increasing molecular size, as by a sieve, with many openings 8 nm and a few 40 to 60 nm wide. In response to local tissue injury or to certain chemical mediators, larger junctional pathways may be opened, greatly increasing permeability to large molecules. Both alveolar capillaries and airway exchange vessels exhibit this response, but the effective stimuli may differ (e.g., alveolar capillaries are insensitive to histamine and bradykinin). Hydrophilic solutes are transported by diffusion, convection, and vesicular exchange (transcytosis). For small ions and molecules (radii < 2 nm), diffusion is the dominant transport mode; contributions of convection and transcytosis are negligibly small. Because diffusion decreases with increasing molecular size, all three mechanisms may contribute substantially to transport of large molecules (radii > 2 nm). Fenestrated endothelia have higher hydraulic conductivities and are more permeable to small ions and molecules than are continuous endothelia. However, their permeabilities to plasma proteins are about the same. Lung alveolar capillary endothelium has lower hydraulic conductivity and lower solute permeabilities than do other continuous endothelia (heart, skeletal muscle). Airway exchange vessel endothelium has about the same permeability to serum albumin as alveolar capillary endothelium. PMID- 1443903 TI - Physiologic control. Anatomy and physiology of the airway circulation. AB - Both for the nose and the lower airways there is an extensive subepithelial capillary network. That for the nose is fenestrated, and this is true for the tracheobronchial tree of rats, guinea pigs, and hamsters, and for that of human asthmatics. However, healthy humans, dogs, and sheep have capillaries without fenestrations except for those close to neuroepithelial bodies and submucosal glands. Deeper in the mucosa there is a capacitance system of vessels, conspicuous in the nose but present also in the lower airways of rabbits and sheep and, to a lesser extent, in those of dogs and humans. Both for the nose and the lower airways, parasympathetic nerves are vasodilator, sympathetic nerves are vasoconstrictor, and sensory nerves are able to release dilator neuropeptides. Most inflammatory and immunologic mediators are vasodilator. A conspicuous difference between the nasal and lower airway vasculatures is the presence of arteriovenous anastomoses only in the former. Countercurrent mechanisms also exist in the nose to increase its efficiency in air conditioning, but they have not been established for the trachea. The pulmonary vasculature could be part of such a system for the bronchi. Distension of the airway vasculature thickens the mucosa, probably both by vascular distension and by edema formation. The latter can lead to exudation into the airway lumen. These processes have not been well quantitated, and the balance sheet of capillary and capacitance vessel volumes, interstitial liquid volume, and exudate volume needs to be worked out in physiologic and pathologic conditions. PMID- 1443904 TI - The transport of albumin: a critique of the vesicular system in transendothelial transport. AB - Although albumin circulating in the plasma can exchange with the contents of the extensive vesicular system of microvascular endothelium, the mechanism and quantitative significance of vesicular transport remains unclear. It has recently been shown that transport of electron opaque tracers can occur via the vesicular system, but the detailed ultrastructure is inconsistent with the transcytotic shuttling of single vesicles. Although most physiologic measurements show a major degree of convective coupling in the microvascular permeation of perfused tissues, recent reports suggest that convective coupling is low when albumin escapes from the intact circulation. Because albumin clearance in these studies is consistent with values calculated from ferritin-labeling of vesicles in perfused microvessels, the possibility remains that macromolecular transendothelial transport occurs through transient communications within the vesicular system. PMID- 1443905 TI - Turnover of hyaluronan in the microcirculation. AB - Hyaluronan in skin, lung, and intestine turns over within a few days and catabolism takes place locally in the tissues, in local lymph nodes, and in the liver. Hyaluronan will affect microcirculatory exchange through its influence on interstitial volume exclusion, hydraulic conductivity, and diffusivity of macromolecules. Prolonged increase in interstitial fluid flux in intestine has been shown to reduce the hyaluronan content, which in turn increases hydraulic conductivity and diffusivity of macromolecules. PMID- 1443906 TI - Infections intensify neurogenic plasma extravasation in the airway mucosa. AB - Stimulation of sensory nerves in the airway mucosa of the rat evokes the release of inflammatory peptides such as substance P, which can increase microvascular permeability, resulting in a phenomenon known as neurogenic plasma extravasation. The change in vascular permeability is mediated by NK-1 receptors and is caused by the formation of gaps between endothelial cells of postcapillary venules and small collecting venules, which are the same vessels as are affected by inflammatory mediators such as histamine and bradykinin. Respiratory tract infections caused by Sendai virus or Mycoplasma pulmonis can intensify neurogenic plasma extravasation in the airway mucosa, as indicated by the amount of microvascular leakage evoked by substance P or capsaicin. M. pulmonis infections can produce a 30-fold increase in the magnitude of neurogenic plasma extravasation, which is evident 4 wk after infection and may be permanent. A proliferation of venules in the airway mucosa and heightened sensitivity of these vessels to inflammatory mediators are key elements of the increase in plasma extravasation. Exposure of M. pulmonis-infected rats to ammonia exacerbates the infections and further augments the responsiveness of mucosal venules to inflammatory mediators. Despite this increased responsiveness, the vessels are not abnormally leaky in the absence of inflammatory stimuli. These findings emphasize the importance of airway infections as factors that can cause a potent, long-lasting increase in the sensitivity of the microvasculature of the airway mucosa to inflammatory mediators. PMID- 1443907 TI - Endothelial cell biology. Adhesion molecules involved in the microvascular inflammatory response. AB - Accumulation of leukocytes in tissues is essential for effective host defense. To fulfill this role the cell must interact with and penetrate the vessel wall and migrate in the tissue. It is now clear that cell adhesion molecules play a crucial role in orchestrating these processes. A number of families of such adhesion molecules that mediate the interaction of circulating leukocytes and vascular endothelial cells have been identified. These include the leukocyte integrins, the selectins, members of the immunoglobulin family, and certain carbohydrates. Studies in vitro have elucidated which of these adhesion molecules are important in the interaction of different leukocyte classes with the endothelium under both basal and stimulated conditions. With the aid of monoclonal antibodies, the role that these molecules play in the interaction of inflammatory cells in the microvasculature in vivo is being assessed. Studies to date have demonstrated the key role of cell adhesion molecules in inflammation. PMID- 1443908 TI - The role of the endothelial cell in leukotriene biosynthesis. AB - Endothelial cells do not contain 5-lipoxygenase and thus are unable to generate LTA4 from arachidonate. Nonetheless, endothelial cells may play an important role in leukotriene synthesis by virtue of their ability to metabolize LTA4 derived from activated polymorphonuclear leukocytes (PMNL) and to modulate PMNL 5 lipoxygenase activity. Porcine aortic endothelial cells were found to metabolize exogenous LTA4 to LTC4, and under some conditions human umbilical vein endothelial cells have been found to generate LTB4. Production of LTB4 by these cells appears to be under poorly understood cellular control, and it remains a controversial area of research. Under physiologic conditions, endothelial cells are in constant contact with circulating PMNL, which are known to generate substantial amounts of LTA4. When these two cell types are coincubated in vitro, clear evidence of transcellular metabolism of PMNL-derived LTA4 to LTC4 by endothelial cells is found. Coincubations produce from two to greater than 10 times more LTC4 than either cell alone. In contrast to these findings, when these cells were activated by the receptor-mediated agonist fMLP, evidence for an endothelial cell inhibition of PMNL 5-lipoxygenase was obtained. Rather than augmentation of LTC4 production, as seen with A23187 activation, coincubation activated by fMLP generated significantly less LTC4 (0.23 +/- 0.08 versus 0.75 +/ 0.39 pmol/10(7) cells). The endothelial cell inhibition was removed when these cells were pretreated with aspirin, suggesting that their major cyclooxygenase product, prostacyclin, acts as a feedback regulator of LT synthesis. When cyclooxygenase was blocked, significant transcellular LTC4 synthesis was once again apparent (1.66 +/- 0.44 pmol/10(7) cells). PMID- 1443909 TI - Heat and water exchange in human airways. AB - The intrathoracic airways of humans play a prominent part in conditioning inspired air. During inspiration the air is warmed and humidified by the movement of heat and water from the mucosa as a direct function of the temperature and vapor pressure gradients that exist. In this process, the mucosa is cooled. During expiration, the gradients are reversed, and heat and water are given back into the airways. At low levels of ventilation, most of the conditioning process takes place in the upper air passages; however, as ventilation rises, more and more of the tracheobronchial tree becomes involved, and incompletely conditioned air penetrates deeply into the distal airways before it is brought to equilibrium with body conditions. It is likely that the heat required to condition the inspired air is derived from the bronchial circulation, but this has not yet been definitely proved. In normal persons, the thermal events associated with the conditioning of inspired air do not produce any changes in pulmonary mechanics. In contrast, in asthmatics, the airway cooling of hyperpnea and the rapid rewarming that develops when hyperpnea is terminated evoke bronchoconstriction. PMID- 1443910 TI - [Vertical transmission of HIV virus infection. Questions and answers for the 90's]. PMID- 1443911 TI - [Pertussis. Study of an epidemic]. AB - Forty-six children seen during 1989 with the clinical diagnosis of Pertussis are reviewed in this study. In 64.5% of the cases the Bordet-Gengou medium nasopharyngeal culture was positive for B. pertussis. Two age groups showed more susceptibility to B. pertussis, children under one year of age (70%) and of more than five years of age (20%). The disease was of more severity among infants younger than two months of age (apnea, choking spells, etc.). Most infants needed to be admitted to the hospital. All patients received therapy with erythromycin, salbutamol (80%) and general supportive medical care. No deaths or other medical sequelae were observed. PMID- 1443912 TI - [Evaluation of microalbuminuria in children]. AB - Microalbuminuria has been shown to be important for the diagnosis and prognosis of glomerular nephropathy. A few studies in normal healthy children were performed. The concentration of albumin was determined in 171 samples of the first morning urine by an immunoturbidimetric method. Microalbumin/creatinine ratio values were 4.07 +/- 0.11 mg/mmol, 1.16 +/- 0.10 mg/mmol and 0.88 +/- 0.11 mg/mmol in children of ages 4 days-1 year, 1-7 years and 7-15 years, respectively. We found a negative inverse correlation (r = 0.31; p < 0.05) between age and microalbumin/creatinine ratio. PMID- 1443913 TI - [Modification of the calculation of risk factors in women, possible carriers of Duchenne muscular dystrophy, based on CPK levels]. AB - We have analyzed the CPK levels in 44 carriers of DMD women, previously diagnosed by using molecular techniques (from a risk population of 133 women), and compare them with the CPK levels of 138 women of a control population. The results obtained show that values higher than the normal level (> 250 mU/ml) are compatible compatible in 99% of the cases with the carrier status (21 women of the carrier population and 1 women of the control population showed values higher than 250 mU/ml). On the other hand, normal values do not distinguish between the healthy and carrier populations (22 women of the carrier population showed normal CPK levels). These results can be very useful in genetic counselling, especially in centers where it is not possible to apply recombinant-DNA techniques. PMID- 1443914 TI - [A new method for the measurement of the anatomical development of the muscle complex of the anus in children with anorectal malformations]. AB - We present a new method for the measurement of the anorectal muscle complex. We studied 40 children with anorectal malformation (14 low and 16 high). Taking the perineal TAC with a rectal probe and quotient called "C": [formula: see text] A "C" value less than 0.31 indicates little development of the anus muscle complex. In 10/26 patients with high malformation, "C" was less than 0.31. All of these patients had fecal incontinence. PMID- 1443915 TI - [Intussusception in the Pediatric Hospital of Coimbra. 13-year results]. AB - We present the results from 233 consecutive patients treated for intussusception at the Children's Hospital of Coimbra over a 13-year period (between 1/6/77 and 31/5/90). Males outnumbered females (66.5% vs 33.5%) and 87.9% of the cases occurred within the first year of life. Among the presenting signs and symptoms, abdominal pain occurred in 87.9% and vomiting in 81.5%. The presence of currant jelly stools was less common, but noted in 67.3%. Hydrostatic barium enema was performed in 94.4% of the patients with the aim being both diagnostic and therapeutic, successful reduction was achieved in 57.7%. One hundred and twenty one patients were operated on with specific pathologic lesion found in 11.5% of them. Complications occurred only in the group submitted to surgery. Six children were reoperated on. Most intussusceptions were of the ileocecocolic variety. The overall recurrence rate was 3.8% (3% recurrent intussusceptions followed barium enema reduction and 0.8% followed manual reduction). Mortality rate was 2.5% (1.7% related to intussusception). PMID- 1443916 TI - [Lipid profiles of children and adolescents in Madrid]. AB - We have studied 2,224 children and adolescents of both sexes, ranging between 2 and 18 years of age, at five schools in the city of Madrid. We determined the lipid profile: total cholesterol (T-C), cholesterol bound to high density lipoproteins (HDL-C), cholesterol bound to low density lipoproteins (LDL-C), cholesterol bound to very low density lipoproteins (VLDL-C), triglycerides (TG), apolipoprotein AI and apolipoprotein B100 (Apo A1 and Apo B100, respectively). In relationship to age and sex, in males, as age increases, there is an elevation in LDL-C and TG and a diminution in T-C, HDL-C, Apo AI and Apo B100. There are no changes in VLDL-C. In females, there is a diminution in LDL-C, TG, Apo-B100 and an increase in HDL-C, Apo AI and T-C, with the increase in T-C being found only in those older than 15 years. PMID- 1443917 TI - [Breast feeding in a metropolitan area: (I). Analysis of the current situation]. AB - In order to elaborate a program to promote breast-feeding, it is necessary to know in advance the difficulties encountered by the mothers in the target population. For this purpose, we surveyed a sample of 400 mothers who were representative of those who gave birth in Mostoles in 1989. We found that 56% of the mothers did not exceed two months of breast-feeding. Breast-feeding was shorter in low-income families. Its duration was influenced by the husband's and grandmother's opinions and also by previous failure with elder siblings. Mothers made their choice of feeding method before getting pregnant. We also found that most health professionals acted unsatisfactorily. Other unfavorable factors included excessive insecurity of the mother and misinformation. PMID- 1443918 TI - [Breast feeding in a metropolitan area: (II). Design for a promotion program]. AB - Because of the importance of breast-feeding in the health of both the mother and child, and taking into consideration its poor situation at the present time, it seems fully justified to start a program to promote breast-feeding. This program basically will consist of training health professionals and in the improvement of both the mother's and hospital's practices. It is necessary to motivate health authorities and to curb the excess in formula promotion. Mass-media should be employed for the promotion of breast-feeding and a system should be implemented to obtain a proper record of the duration of breast-feeding. PMID- 1443919 TI - [Children at risk. Our experience]. AB - Seventy children in a situation of risk, evaluated and treated in the Social Work Unit of the Children's Hospital "Virgen del Rocio" over a period of 22 months, were analyzed. Of these children, 89% corresponded to low-middle, low or very low social classes. The most common problems included those of the family (77.1%) with history of maltreatment and unwanted pregnancies being the most prevalent problems. In second place was the personal pathology of the parents (74.2%), with mental disorders and alcoholism being the main causes, followed by drug addiction and delinquency. Social factors (57.1%), which included predominantly unemployment and illiteracy, were the next most common finding. The final factor was the personal pathology of the child (10%). The consequences of the risk situation are described, emphasizing the psychic and treatment carried out. Final comments are made underlining the importance of awareness and professional training, multiprofessional teams, means of detecting and intervention into the problems, manpower and material as well as how to carry out studies in this area. PMID- 1443920 TI - [Early diagnosis of HIV infection in children born to seropositive mothers]. AB - We have studied 70 children, born to HIV seropositive mothers, since the first trimester of life and every three months thereafter. The virological markers we used in the diagnosis included: 1) p24 antigen detection. 2) Autochthonous production of antibodies detected by Western Blot technique. 3) HIV isolation. 4) Specific determination of IgM antibodies. In infected children under 15 months of age, p24 antigen was positive in 78%, HIV was isolated in 75% and autochthonous production of antibodies occurred in 50%. IgM specific antibodies were detected in 92%, but these were also detected in the 33% of the children who seroreverted. In seroreverted children, the other three virological markers were negative. The problems due to the low sensitivity in p24 antigen detection, HIV isolation and the detection of autochthonous production of antibodies, as well as the low specificity of the IgM detection, means that it is necessary to simultaneously use several techniques in the diagnosis of these children. PMID- 1443921 TI - [Neurofibromatosis as a cause of arterial hypertension in children]. AB - Hypertension can complicate the course of neurofibromatosis. When it appears in adulthood (after 18 years of age) it is usually due to pheochromocytoma, but in children the cause is a stenotic lesion of the renal arteries or the suprarenal aorta. Its treatment follows the general principles used in the treatment of the more common forms of renovascular hypertension. We report four patients that developed renovascular hypertension after being diagnosed of neurofibromatosis, they had different localizations of the stenotic lesion, and the diverse types of surgical treatment are analyzed. PMID- 1443922 TI - [Diagnostic evaluation of cervical adenopathies in childhood]. AB - Between 1985 and 1990, 45 children were studied in an inpatient basis hospital because of cervical lymphadenopathy. This was the most important clinical sign in these patients. Forty-three had true adenitis. In the others, one was submaxillitis and one a sarcoma. The age range was from 2.1 to 13.3 years. Seven children (16%) had neoplastic adenitis (2 papillary carcinoma of the thyroid, 4 Hodgkin's lymphoma and one non-Hodgkin's lymphoma). Thirty-six patients had benign disorders (18 mononucleosis infections, 7 nonspecific adenitis, 5 infections of mycobacteria, 2 of toxoplasma and 2 of rickettsia, one cervical Whipple and one desmopathic adenitis). We did no find any differences related to age or morphological characteristics of the lymph nodes. The evolution time in patients with malignant tumors was 16.4 weeks and 9.6 weeks in the benign group. All of the cases with supraclavicular location had a lymphoma. The mean LDH in patients with malignant tumors was 214 U/L and 614 U/L in those with non malignant tumors (p < 0.01). PMID- 1443923 TI - [Hepatitis associated with measles virus]. PMID- 1443924 TI - [Shwachman syndrome: apropos of a case of atypical presentation]. PMID- 1443925 TI - [Congenital esophageal stenosis associated with H-shaped tracheo-esophageal fistula]. PMID- 1443926 TI - [Gianotti-Crosti syndrome]. PMID- 1443927 TI - [Incontinentia pigmenti]. PMID- 1443928 TI - [Recovery from delayed puberty in a case of prolactinoma]. PMID- 1443929 TI - [Cutaneous cellular hemangioma in childhood, clinical and pathological peculiarities of the tumor]. PMID- 1443930 TI - [Cardiac tamponade and central venous catheterization]. PMID- 1443931 TI - [Treatment of tuberculosis in children and adolescents]. PMID- 1443932 TI - [Primary dyslipoproteinemias in a child-adolescent population of Aragon detected by two methods: selective search and targeted search]. AB - A series of 439 children (245 boys and 194 girls) ranged between 2.0 and 18.0 years of age have been studied January 1987 to April 1990. They belonged to four groups: I) 306 children (163 boys and 143 girls), "control group"; II) 31 children (22 boys and 9 girls) whose parents had some type of dyslipoproteinemia (HPDLP); III) 38 children (24 boys and 14 girls) whose fathers were survivors of myocardial infarction occurred before 55 years of age (HPCI); and IV) 43 children (23 boys and 20 girls) who had, at least in two occasions, more than three months of time separated between then, over 200 mg/dL of total serum cholesterol levels detected by opportunist search (HDC). For children's identification of risk factors to develop atherosclerotic disease during adult life, two different types of strategy has been utilised. One, "selective search", taking into account children of groups II (HPDLP) and III (HPCI). Other, "opportunist search", taking into consideration children of group IV (HDC). The most frequent primary dyslipoproteinemia between the families of children with high serum levels has been Polygenic Hypercholesterolemia (HP). In the second place were both Familial Hypercholesterolemia (HF) an Familial Combined Hyperlipidemia (HFC). A family with Mixed Hyperlipidemia (HM) was also identified. Familial aggregation, with relation to serum lipid levels, were detected in children of the three groups: HPDLP, HPCI and HDC, as it is reported by another authors. Our results suggest the genetic alterations may contribute to the presence of different types of dyslipoproteinemia in children. PMID- 1443933 TI - [Poliomyelitis vaccination and immunization status of school children. School Health Team of the Center of Health Promotion]. AB - This study presents the results of a vaccination inquire in 2,078 schoolchildren: 807 students in the first year of General Basic Education (G.B.E.) and 1,227 students in the last year of G.B.E. attending public and private schools of the Council of Madrid. The presence of antibodies against the three polio-viruses was determined in 1,509 schoolchildren. About 68.3% of the students received the complete schedule of vaccinations, with 84.7% belonging the group of children in the first year of G.B.E. and 51.2% belonging to that in the last year of G.B.E. (p < 0.01). The percentage of children immunized against the three polioviruses was 92.7%, with 94% of the students in the first year of G.B.E. being immunized and 92% of those in the last year of G.B.E. (p < 0.01). We found differences in the immunization rate between those students receiving more or less than three doses of vaccine. We compared our study with other seroepidemiologic studies undertaken in our country. PMID- 1443934 TI - [Neonatal care in a primary health care center]. AB - Small Madrid community hospitals (less than 100 deliveries annually) were the site of approximately 14% of the hospital births in 1990. The quality and quantity of services provided by our unit, considered to be of the first of primary level, are presented. The study period was 2.5 years long and 1,339 newborns were attended. The mean stay in the neonatal unit was 4.44 days (+/- 3.8 days). The cesarean section rate was 17%. The incidence of newborns with a weight less than 2,000 g was 1.5%, while those with a weight of more than 4,000 g was 5.47%. Almost 25% of the newborns were transferred to the neonatal ward and 1.79% were transferred to a third level hospital (neonatal intensive care), where three of them died. The mortality rate in our hospital was null. With rational guidelines, the primary centers can provide valuable services in a community perinatal care system. PMID- 1443935 TI - [Dog bites in children. Epidemiologic and clinical study of 144 cases]. AB - We have done a prospective study of 144 cases of dog bites in children between 1 and 13 years of age that were attended at the Emergency Department of the "Miguel Servet" Children's Hospital of Zaragoza over a period of 30 months. The average child is an 8 year old boy who is bitten at 4 p.m. in the lower limbs by a dog belonging to either the family, a neighbor, or to some friends. The dog of unknown breed and the German shepherd are those most frequently involved (39.5% and 22.2%, respectively). There is a low incidence of infection (4.8%). The attacks were provoked by petting in 52.7%; therefore, we recommend not to get close to the animals even if they are known. In our area, 83.3% of the children are correctly vaccinated. Finally, we compare our results with other studies and we suggest that it is of great interest to establish measures in order to reduce the incidence of dog bites. PMID- 1443936 TI - [Radiological parameters indicating normalization of bone lesions in Langerhans cell histiocytosis]. AB - The signs predicting radiological healing were studied in 35 bone lesions of 12 children with Langerhans' cell histiocytosis. The earliest and more frequent radiological signs predicting healing were a decrease in size (52%), the change from a non-sclerotic lesion to one with sclerosis (41%) and the loss of distinct margins of the lesions (29%) three months after diagnosis. The first of these signs was statistically significant after three months of follow-up, the last two after 12 months. The trabecular pattern was a late (one case after 2 years) and infrequent (observed in only 24% of lesions) sign of radiological healing. PMID- 1443937 TI - [Cardiovascular risk in the pediatric population. Plasma fatty acid levels]. AB - Thirty-seven offspring of patients who had acute myocardial infarctions were investigated. Serum fatty acids of the whole plasma lipids were evaluated within the frame of a full biochemical assessment. Baseline values were obtained and the children were subsequently put on appropriate diets and advised to cut-out smoking and alcohol. The same values were obtained following one year on such a regimen. Results were compared with those found in a control group. Baseline palmitoleic and dihomogammalinolenic acid serum levels were significantly raised in the study group. Values of palmitoleic, but not of dihomogammalinolenic acid, had returned to normal by the reassessment one year later. PMID- 1443938 TI - [Blood lipids in children up to 12 years of age in a rural population from Extremadura]. AB - We have studied the levels of total cholesterol and triglycerides in 398 children of both sexes, ranging in age from birth until 12 years, in a rural population from Extremadura (Spain). The measurements have been made when analyses were indicated for other reasons. We obtained the following mean values: Total cholesterol = 170.8 +/- 37.0 mg/dl in boys and 172.6 +/- 31.7 mg/dl in girls. Of these children, 43.5% had levels over the limit of 175 mg/dl. Triglycerides = 75.1 +/- 33.5 mg/dl in boys and 71.1 +/- 36.2 mg/dl in girls. In 14.2% of the children this value was over 100 mg/dl. The lipoprotein levels did not present any significant differences with respect to sex until 12 years of age. We compare our results to those of other authors. PMID- 1443939 TI - [Celiac disease and short stature in children]. AB - Celiac disease (CD) is a known cause of short stature and sometimes, this is its only symptom. The aim of this work was to determine the incidence of CD in children with short stature. We studied 178 infants with short stature and with no gastrointestinal symptoms. Serum IgA antigliadin antibodies were determined in all of them. We found a pathological titer in ten of these patients. Peroral intestinal biopsy was performed on these children, with nine showing no alterations and only one having subtotal villus atrophy that was compatible with CD. Therefore, the incidence of CD in this population is about 0.56%, which is much lower than the incidence shown by other authors. PMID- 1443940 TI - [Dermatitis herpetiformis vs. celiac disease]. AB - Twenty-nine patients affected with dermatitis herpetiformis (HD), all of whom were on a diet including gluten, were investigated for symptoms of enteropathy. Of these patients, 71% presented severe intestinal lesions, indistinguishable from those found in coeliac disease (CD). However, there were little other clinical manifestations of this finding since only three children in this group had weight and height < or = P3. Of the remaining children, 18% had moderate intestinal atrophy and 10% had normal mucosa or mucosa with negligible changes. When changed to a gluten free diet, the intestinal lesions subsided, dermic lesions disappeared in 17 patients, improved in 8 others and remained the same in the other three patients that were still on variable diets. A study of human leukocyte antigens (HLA) class II showed a total association with Dqw2 and 85% association to DR3, which was identical to the coeliac disease control group. These findings lead one to conclude that HD and CD are different clinical expressions of the same sensitivity to gluten which is associated to an immunological disorder with a common genetic base linked to certain HLA molecules. PMID- 1443941 TI - [Objective evaluation of a pediatric intensive care unit without continuous attendance (I)]. AB - Eight-hundred and nine consecutive admissions have been reexamined by means of analysis of record cards made out at the moment of discharge from the ICU, in which, among other data, the TISS and PSI maximum for the first six hours from admission are included. The results obtained are the following: 50% of the admissions were classified as medium care (PSI < 5, TISS < 20), 28% were grade IV (PSI > 12, TISS > 40), and half were of grade III with a PSI of 9.38 and a TISS of 20.29. The overall mortality was 8.9%. However, the mortality for grades III+IV was 13.4% and gave a good correlation with the PSI, but not with the TISS. The PSI/TISS ratio was 0.45 and the predicted mortality rate according to the PSI was 6.1% for grade III and greater than 12% for grade IV. We conclude the following: (1) Of the illness, 28% were grade IV. (2) We observed a deficient PSI/TISS ratio. (3) The evaluation has to be done by objective means in which the capability of carrying out different methodologies has not been taken into account. PMID- 1443942 TI - [Preoperative ultrasonic diagnosis in hepatic hamartoma]. PMID- 1443943 TI - [Hemimegalencephaly. Presentation of a case uncommon in neonatal age]. PMID- 1443944 TI - [Ingestion of alkaline batteries: a better alternative for their extraction]. PMID- 1443945 TI - [Septo-optic dysplasia: absence of the hypophysial stalk in the MRI image]. PMID- 1443946 TI - [Mucocele: a form of manifestation of cystic fibrosis in childhood. Review of the literature]. PMID- 1443947 TI - [Benign familial hyperphosphatasemia]. PMID- 1443948 TI - [Acquired angular deformity of the index finger due to fingersucking]. PMID- 1443949 TI - Postoperative hyponatremic encephalopathy in menstruant women. AB - OBJECTIVES: To determine factors associated with the development of encephalopathy and with its clinical course in patients with postoperative hyponatremia. SETTING: Consultation and referral services of two university medical centers and community hospitals. DESIGN: Case-control study (risk factors for encephalopathy) and cohort study (clinical course among patients with encephalopathy). PATIENTS: Case patients included 65 adults with postoperative hyponatremic encephalopathy; controls included 674 adult patients who had postoperative hyponatremia without encephalopathy and who were selected from 76,678 consecutive adult surgical inpatients. MEASUREMENTS: Age, gender, menstrual status, neurologic symptoms, time to development and degree of hyponatremia, arterial blood gas determinations, serum chemistries, morbidity and mortality. RESULTS: Case patients included 40 women (62%) and 25 men (38%) (P > 0.05); controls included 367 women (54%) and 307 men (46%) (P > 0.1). Of the 34 case patients who developed permanent brain damage or died, 33 (97%) were women (P < 0.001). Among the women with brain damage, 25 (76%) were menstruant (P < 0.001). The relative risk for death or permanent brain damage from hyponatremic encephalopathy in women compared with men was 28 (95% Cl, 5 to 141) and in menstruant women compared with postmenopausal women, 26 (Cl, 11 to 62). Arterial PO2 at diagnosis was significantly lower in female than in male case patients (34 +/- 5 compared with 91 +/- 3 mm Hg; P < 0.001). Further, of the 38 case patients who had respiratory arrest before the diagnosis of hyponatremic encephalopathy, 36 (95%) were women. Extent of or time to development of hyponatremia did not correlate with subsequent brain damage (P > 0.1). CONCLUSIONS: Women and men are equally likely to develop hyponatremia and hyponatremic encephalopathy after surgery. However, when hyponatremic encephalopathy develops, menstruant women are about 25 times more likely to die or have permanent brain damage compared with either men or postmenopausal women. PMID- 1443950 TI - Causes of persistent dizziness. A prospective study of 100 patients in ambulatory care. AB - OBJECTIVE: To determine the causes of persistent dizziness in outpatients. DESIGN: Consecutive adult outpatients presenting with a chief complaint of dizziness. SETTING: Four clinics (internal medicine, walk-in, emergency room, and neurology) in a teaching hospital. PATIENTS: Of 185 patients presenting during the 10-month study period, 51 (28%) had minimal or no dizziness at 2-week follow up. Of the remaining 134 patients, 100 completed the study protocol (mean age, 62 years; range, 20 to 85 years). MEASUREMENTS: Evaluation included a detailed study questionnaire, standardized physical examination, vestibular testing by a neuro ophthalmologist, laboratory tests, audiometry, and a structured psychiatric interview. Data were abstracted onto a standard form and reviewed by three raters. Raters independently assigned diagnoses using explicit criteria, with the final cause determined by consensus. RESULTS: Primary causes of dizziness included vestibular disorders (54 patients), psychiatric disorders (16 patients), presyncope (6 patients), dysequilibrium (2 patients), and hyperventilation (1 patient); dizziness was multicausal in 13 patients and of unknown cause in 8 patients. Many of those with a single primary cause, however, had at least one other condition contributing to their dizziness; only 52% of patients had a single "pure" cause. Thirty patients had a potentially treatable primary cause, the most common being benign positional vertigo (BPV) (16%) and psychiatric disorders (6%). Central vestibulopathies detected in 10 patients were presumably vascular or idiopathic in origin. No brain tumors or cardiac arrhythmias were found. CONCLUSIONS: Vestibular disease and psychiatric disorders are the most common causes of persistent dizziness in outpatients. In about 50% of patients with dizziness, more than one factor causes or aggravates symptoms. Life threatening causes were rare, even in our elderly population. PMID- 1443951 TI - Effect of HIV antibody testing and AIDS education on communication about HIV risk and sexual behavior. A randomized, controlled trial in college students. AB - OBJECTIVE: To evaluate the effects of human immunodeficiency virus (HIV) antibody testing and education about HIV infection on communication about sexual risk behaviors for HIV transmission. DESIGN: Randomized, controlled trial with three arms. SETTING: University student health center. PATIENTS: Of 2196 heterosexual university students attending the student health clinic for medical care, 435 were interested in education about HIV and HIV testing and were randomly assigned to three groups. Follow-up at 6 months was done in 370 subjects (85%): 90 control subjects, 144 subjects who received education alone, and 136 subjects who received education plus HIV testing. MEASUREMENTS AND RESULTS: Subjects who received HIV testing plus education questioned sexual partners about their HIV status more than subjects receiving education alone or those in the control group (56%, 42%, and 41% of subjects, respectively; P = 0.01). No consistent differences among groups in the number of sexual partners or in the use of condoms were found at follow-up. CONCLUSIONS: Heterosexual university students who received education about HIV infection plus HIV testing had increased communication with sexual partners about the risk for HIV infection after 6 months. Further reduction in risk behaviors for HIV transmission may require additional interventions in this population. PMID- 1443952 TI - Stunned myocardium in the toxic shock syndrome. PMID- 1443953 TI - Myocardial stunning after electroconvulsive therapy. PMID- 1443954 TI - Measured enthusiasm: does the method of reporting trial results alter perceptions of therapeutic effectiveness? AB - OBJECTIVE: To compare clinicians' ratings of therapeutic effectiveness when different trial end points were presented as percent reductions in relative compared with absolute risk and as numbers of patients treated to avoid one adverse outcome. DESIGN: Survey, with random allocation of two questionnaires. SETTING: Toronto teaching hospitals. RESPONDENTS: Convenience sample of 100 faculty and housestaff in internal medicine and family medicine. INTERVENTION: One questionnaire presented results for three end points of the Helsinki Heart Study as separate drug trials using only absolute differences in events; the other showed the same end points as relative differences. Both questionnaires included a fourth "trial," showing person-years of treatment needed to prevent one myocardial infarction. MAIN OUTCOME MEASURE: The "trials" were each rated on an 11-point scale, from treatment "harmful" to "very effective." RESULTS: Respondents' ratings of effectiveness varied with the end point. Controlling for end point, ratings of effectiveness by the 50 participants receiving absolute event data were lower than those by 50 participants responding to relative risk reductions (P < 0.001); however, no end-point difference was more than 0.6 scale points. For a "trial" reporting that 77 persons were treated for 5 years to prevent one myocardial infarction, mean ratings were 2.3 or 1.8 scale points lower, respectively (both P < 0.001), than when the same data were shown as relative or absolute risk reductions. CONCLUSIONS: Clinicians' views of drug therapies are affected by the common use of relative risk reductions in both trial reports and advertisements, by end-point emphasis, and, above all, by underuse of summary measures that relate treatment burden to therapeutic yields in a clinically relevant manner. PMID- 1443955 TI - Transesophageal echocardiography in the evaluation of stroke. AB - OBJECTIVE: To review the current role of transesophageal echocardiography in the evaluation of stroke. DATA IDENTIFICATION: Articles examining the role of transesophageal echocardiography for evaluation of patients with stroke were identified using computer and bibliography searches. STUDY SELECTION: All English language articles that provided full details on patient selection criteria, methods, and study design were reviewed. RESULTS OF DATA ANALYSIS: Cardiogenic embolism is frequently an uncertain diagnosis merely inferred by finding a potential cardiac source. Transthoracic echocardiography has had a low yield in screening unselected patients with stroke. Several series of patients with stroke have been reported comparing transthoracic and transesophageal echocardiography. Potential cardiac sources of embolism were consistently identified in many more patients by transesophageal echocardiography. Many findings are, however, of uncertain significance; these include spontaneous echo contrast, patent foramen ovale, filamentous strands on the mitral valve, and atrial septal aneurysm. CONCLUSIONS: Transesophageal echocardiography is most helpful in patients with stroke who are less than 45 years of age and in those without clinical evidence of heart disease. The indications for its use in the evaluation of stroke remain controversial. Further studies are needed using transesophageal echocardiography in patients with stroke and in control groups, not only to determine the natural history of transesophageal, echocardiographically detected abnormalities but also to evaluate treatment options. PMID- 1443956 TI - Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I). AB - PURPOSE: To review the clinical, epidemiologic, immunologic, and virologic aspects of the chronic myelopathy associated with human T-cell leukemia/lymphoma virus type I (HTLV-I), currently called tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). DATA IDENTIFICATION: Studies done after 1985, when TSP/HAM was first recognized, were identified by a computer search using MEDLARS II and CANCERLIT. Additional information was acquired from personal files and bibliographies of existing literature. STUDY SELECTION: A total of 400 articles, 90 book chapters, and 150 abstracts from meetings covering all aspects of HTLV-I and neurologic diseases were critically analyzed, and information from 250 publications was included. RESULTS OF DATA ANALYSIS: TSP/HAM is present in most HTLV-I endemic areas, with a prevalence ranging from 5.1 to 128 per 100,000 inhabitants. Up to 20% of patients develop TSP/HAM after transfusion of HTLV-I contaminated blood. Pathologic characteristics indicate a chronic meningomyelitis. The clinical features consist of a chronic progressive spastic paraparesis or paraplegia, sphincter disturbances, and minimal sensory loss. Supraspinal and peripheral nerve involvement is sometimes observed. High titers of HTLV-I-specific antibodies are present in the serum and cerebrospinal fluid. The high level of humoral and cellular immunologic response and the association of TSP/HAM with other immunologic diseases suggest an immune-mediated process. Corticosteroids and immunosuppressor treatment usually result in only short-term improvement. CONCLUSION: TSP/HAM is a common neurologic disease in many parts of the world. All patients with chronic progressive myelopathies should be tested for serum and cerebrospinal fluid HTLV-I-specific antibodies. Systematic screening of blood donors for HTLV-I is necessary to help prevent the dissemination of the virus and the occurrence of post-transfusional cases. PMID- 1443957 TI - American College of Physicians Ethics Manual. Third edition. AB - Medicine, law, and social values are not static and must be re-examined periodically. This edition of the ACP Ethics Manual covers emerging issues in medical ethics and revisits some old issues. The overview of the evolution of medical ethics, which appeared in previous editions of the Manual, has been eliminated to allow more space for the consideration of today's ethical dilemmas. Other changes include a revised chapter on end-of-life care, discussion of physician-assisted suicide, revised sections on conflicts of interest and on medical risk to the physician and patient, given developments in human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS), and discussion of sexual contact between physician and patient. A statement on disclosure of errors and a section on care of the physician's family have also been added. The sections on confidential information told by a patient's family or friend to the physician; on physician-pharmaceutical industry relations; on physicians in training; and on the impaired physician have been expanded. Sections on advertising, peer review, and resource allocation have been revised. The literature of biomedical ethics expands at a rate that does not allow a bibliography to remain current, so an exhaustive list of references or suggested readings is not included in this manual. Instead, only cited references are listed. PMID- 1443958 TI - Breast cancer screening among women from 65 to 74 years of age in 1987-88 and 1991. NCI Breast Cancer Screening Consortium. AB - OBJECTIVE: To compare breast cancer screening rates from the 1991 survey with data from 1987-88 for women aged 65 to 74. DESIGN: Surveys of women from five communities. SETTINGS: Five control communities of the National Cancer Institute's Breast Cancer Screening Consortium. PARTICIPANTS: White, non-Hispanic women, ages 65 to 74; 499 in 1987-88 and 2156 in 1991. Response rates for the first survey wave ranged by area from 65% to 77% and for the second survey wave, from 62% to 85%. MAIN OUTCOME MEASURE: Mammogram and clinical breast examination during the past year and performance of monthly breast self examination, with the screening rates in wave 2 directly standardized to the income and education distribution of wave 1 in each area. RESULTS: Mammography use between waves increased significantly (P < 0.05 after adjusting for education, income, and age) in all but one area (from 19% to 33% in wave 1 to 35% to 59% in wave 2). Among women who had a mammogram, the percent who also had a clinical breast examination decreased between waves from 95% to 85% (P = 0.001). CONCLUSIONS: Mammography in older women increased dramatically over 3 years, although the use of clinical breast examination may be decreasing. PMID- 1443959 TI - A proposed trial of amiodarone for atrial fibrillation. PMID- 1443960 TI - AIDS-associated illness and HIV negativity. PMID- 1443961 TI - Internal medicine curriculum reform. PMID- 1443962 TI - Internal medicine curriculum reform. PMID- 1443963 TI - Internal medicine curriculum reform. PMID- 1443964 TI - Internal medicine curriculum reform. PMID- 1443965 TI - Internal medicine curriculum reform. PMID- 1443966 TI - Handicapping the handicapped. PMID- 1443967 TI - Internal medicine curriculum reform. PMID- 1443968 TI - Emotional support and survival after myocardial infarction. A prospective, population-based study of the elderly. AB - OBJECTIVE: To compare the survival of elderly patients hospitalized for acute myocardial infarction who have emotional support with that of patients who lack such support, while controlling for severity of disease, comorbidity, and functional status. DESIGN: A prospective, community-based cohort study. SETTING: Two hospitals in New Haven, Connecticut. PATIENTS: Men (n = 100) and women (n = 94) 65 years of age or more hospitalized for acute myocardial infarction between 1982 and 1988. MEASUREMENTS: Social support, age, gender, race, education, marital status, living arrangements, presence of depression, smoking history, weight, and physical function were assessed prospectively using questionnaires. The presence of congestive heart failure, pulmonary edema, and cardiogenic shock; the position of infarction; in-hospital complications; and history of myocardial infarction were assessed using medical records. Comorbidity was defined using an index based on the presence of eight conditions. RESULTS: Of 194 patients, 76 (39%) died in the first 6 months after myocardial infarction. In multiple logistic regression analyses, lack of emotional support was significantly associated with 6-month mortality (odds ratio, 2.9; 95% CI, 1.2 to 6.9) after controlling for severity of myocardial infarction, comorbidity, risk factors such as smoking and hypertension, and sociodemographic factors. CONCLUSIONS: When emotional support was assessed before myocardial infarction, it was independently related to risk for death in the subsequent 6 months. PMID- 1443969 TI - Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. AB - OBJECTIVE: To determine whether simultaneous ingestion of ferrous sulfate and thyroxine reduces the efficacy of thyroid hormone in patients with primary hypothyroidism. DESIGN: Uncontrolled clinical trial. SETTING: Outpatient research clinic of a tertiary care center. PATIENTS: Fourteen patients with established primary hypothyroidism on stable thyroxine replacement. INTERVENTION: All patients were instructed to ingest simultaneously, a 300-mg ferrous sulfate tablet and their usual thyroxine dose every day for 12 weeks. RESULTS: After 12 weeks of ferrous sulfate ingestion with thyroxine, the mean level of serum thyrotropin (thyroid stimulating hormone, TSH) rose from 1.6 +/- 0.4 to 5.4 +/- 2.8 mU/L (P < 0.01), but the free thyroxine index did not change significantly. Subjective evaluation using a clinical score showed that nine patients had an increase in symptoms and signs of hypothyroidism; the mean score for the 14 patients changed from 0 to 1.3 +/- 0.4 (P = 0.011). When iron and thyroxine were mixed together in vitro, a poorly soluble purple complex appeared that indicated the binding of iron to thyroxine. CONCLUSIONS: Simultaneous ingestion of ferrous sulfate and thyroxine causes a variable reduction in thyroxine efficacy that is clinically significant in some patients. The interaction is probably caused by the binding of iron to thyroxine. PMID- 1443970 TI - Myxedema-associated cardiogenic shock treated with intravenous triiodothyronine. PMID- 1443971 TI - Hormone therapy to prevent disease and prolong life in postmenopausal women. AB - PURPOSE: To critically review the risks and benefits of hormone therapy for asymptomatic postmenopausal women who are considering long-term hormone therapy to prevent disease or to prolong life. DATA SOURCES: Review of the English language literature since 1970 on the effect of estrogen therapy and estrogen plus progestin therapy on endometrial cancer, breast cancer, coronary heart disease, osteoporosis, and stroke. We used standard meta-analytic statistical methods to pool estimates from studies to determine summary relative risks for these diseases in hormone users and modified lifetable methods to estimate changes in lifetime probability and life expectancy due to use of hormone regimens. RESULTS: There is evidence that estrogen therapy decreases risk for coronary heart disease and for hip fracture, but long-term estrogen therapy increases risk for endometrial cancer and may be associated with a small increase in risk for breast cancer. The increase in endometrial cancer risk can probably be avoided by adding a progestin to the estrogen regimen for women who have a uterus, but the effects of combination hormones on risk for other diseases has not been adequately studied. We present estimates for changes in lifetime probabilities of disease and life expectancy due to hormone therapy in women who have had a hysterectomy; with coronary heart disease; and at increased risk for coronary heart disease, hip fracture, and breast cancer. CONCLUSIONS: Hormone therapy should probably be recommended for women who have had a hysterectomy and for those with coronary heart disease or at high risk for coronary heart disease. For other women, the best course of action is unclear. PMID- 1443972 TI - Guidelines for counseling postmenopausal women about preventive hormone therapy. American College of Physicians. PMID- 1443973 TI - Kath. PMID- 1443974 TI - The pathogenesis of gastroesophageal reflux disease: a challenge in clinical physiology. PMID- 1443975 TI - Asymptomatic ventricular arrhythmias in healthy persons: smoke or smoke screen? PMID- 1443976 TI - Diagnosing the irritable bowel syndrome. PMID- 1443977 TI - Diagnosing the irritable bowel syndrome. PMID- 1443978 TI - Acromegaly and pituitary carcinoma. PMID- 1443979 TI - Diclofenac-induced isolated myonecrosis and the Nicolau syndrome. PMID- 1443980 TI - Paresthesias and mefloquine prophylaxis. PMID- 1443981 TI - Consistency in prescription writing. PMID- 1443983 TI - "Playing God" as an act of hope. PMID- 1443982 TI - Physicians and cost control. PMID- 1443984 TI - Determinants of gastroesophageal junction incompetence: hiatal hernia, lower esophageal sphincter, or both? AB - OBJECTIVE: To examine the effects of hiatal hernia and lower esophageal sphincter (LES) pressure on the competence of the gastroesophageal junction under conditions of abrupt increases in intra-abdominal pressure. DESIGN: Acute experiments. SETTING: University-hospital-based gastroenterology practice. PARTICIPANTS: Sixteen asymptomatic volunteers and 34 patients with endoscopic findings suggestive of hiatal hernia. INTERVENTION: A series of eight provocative maneuvers entailing abrupt changes in intra-abdominal pressure. MEASUREMENTS: Five radiographic measurements relevant to the presence and extent of hiatal hernia were made from videotaped barium-swallow examinations. Lower esophageal sphincter pressure was measured immediately before each maneuver. The percentage of maneuvers that resulted in gastroesophageal reflux was calculated as the reflux score. A stepwise regression analysis was then used to model the relation between measured variables of the gastroesophageal junction (manometric and radiographic) with reflux score. RESULTS: Patients with hiatal hernia had substantially higher reflux scores and lower LES pressures than either patients without hernias or volunteers. In diminishing order of significance, the terms in the model of susceptibility to reflux were axial length of hernia measured between swallows; LES pressure; and an interaction term in which a progressive increase occurred in the risk for reflux associated with a hypotensive lower esophageal sphincter as hernia size increased. CONCLUSIONS: Gastroesophageal junction competence during abrupt increases in intra-abdominal pressure is compromised by both hiatal hernia and low LES pressure. These factors interact with each other to determine susceptibility to reflux. PMID- 1443985 TI - Kidney transplantation from living unrelated donors. AB - OBJECTIVE: To compare patient and graft survival of recipients of kidneys from living, unrelated donors (LUDs); cadaveric donors; and living, related donors (LRDs) matched for zero (mismatched), one, or two (identical) haplotypes. DESIGN: Cohort study. SETTING: Sixty-three renal transplantation centers affiliated with the Brazilian Transplantation Registry (accounting for more than 95% of the transplantation activity in Brazil). PATIENTS: Patients having renal transplantation between January 1987 and March 1991. Of 2892 patients, 165 (6%) received transplants from LUDs; 964 (33%), from cadaveric donors; 183 (6%), from zero haplotype, HLA-matched LRDs; 1259 (44%), from one haplotype-matched LRDs; and 321 (11%), from two haplotype-matched LRDs. MEASUREMENTS: Patient and graft survival. Patients were followed for an average of 15.8 months. RESULTS: After adjustment for age, race, diagnosis of primary disease, history of previous transplantation, cyclosporine use, and number of transplants from LUDs per center, patient survival did not differ statistically for recipients of kidneys from LUDs and recipients of cadaveric kidneys (risk ratio [RR], 1.16; 95% Cl, 0.68 to 1.98). Little difference was seen between the adjusted death rate for recipients of zero haplotype-matched LRDs and recipients of cadaveric kidneys (RR, 1.13; Cl, 0.69 to 1.87). Similarly, in a multivariate analysis, recipients of kidneys taken from LUDs and zero haplotype-matched LRDs had a risk for graft failure that did not differ statistically from that of cadaveric kidney recipients (RR, 0.74; Cl, 0.45 to 1.22 and RR, 0.82; Cl, 0.53 to 1.25, respectively). CONCLUSIONS: Graft survival for recipients of kidneys from LUDs is similar to that from zero haplotype-matched LRDs and is at least as good as that achieved with cadaveric transplants. PMID- 1443986 TI - Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. AB - OBJECTIVE: To determine whether the presence of anticardiolipin antibodies is a risk factor for ischemic stroke and venous thrombosis in healthy adult men. DESIGN: A nested, case-control study in a prospective cohort. SETTING: A nationwide study of physicians. PARTICIPANTS: The study sample was drawn from the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 male physicians. At entry, 68% of the participants submitted plasma samples that were subsequently frozen at -80 degrees C. During 60.2 months of follow-up, follow-up for nonfatal outcomes was 99.7% complete and ascertainment of fatal outcomes was 100% complete. We identified men with documented ischemic stroke, deep venous thrombosis of the leg, or pulmonary embolus and for whom a plasma sample was available. A control was matched by age, smoking history, and length of follow-up to each of the 100 patients with ischemic stroke and the 90 patients with deep venous thrombosis or pulmonary embolus. MEASUREMENTS: Plasma samples were assessed for IgG anticardiolipin antibodies by enzyme-linked immunosorbent assay. The mean anticardiolipin antibody titers of the case patients in the two diagnostic groups (ischemic stroke; venous thrombosis or pulmonary embolus) were compared with those of the control groups, and relative risks were calculated for patients in increasing percentile categories of anticardiolipin antibodies by conditional logistic regression. RESULTS: The anticardiolipin antibody titers were higher in case patients with deep venous thrombosis and pulmonary embolus than in their matched controls (P = 0.01). Persons with anticardiolipin antibody titers above the 95th percentile had a relative risk for developing deep venous thrombosis or pulmonary embolus of 5.3 (95% CI, 1.55 to 18.3; P = 0.01). The anticardiolipin antibody titers in case patients with ischemic stroke and controls were not significantly different (P > 0.2), and no clear trend of higher risks among those with elevated levels of anticardiolipin antibodies was observed. CONCLUSION: An anticardiolipin antibody level above the 95th percentile is an important risk factor for deep venous thrombosis or pulmonary embolus but not for ischemic stroke in healthy adult men. PMID- 1443987 TI - [Rectal cancer. Introduction]. PMID- 1443988 TI - [Forms of the diffusion of rectal cancer and principles of surgical radicality]. PMID- 1443989 TI - [Role of lymph node excision in the treatment of rectal cancer]. PMID- 1443990 TI - [Low anterior resection in the curative surgical treatment of rectal cancer]. AB - Abdominoperineal resection for rectal cancer are being performed with decreasing frequency in favour of sphincter-saving resections. It remains to be demonstrated that sphincter preservation has not resulted in compromised local disease control and survival. For this purpose 342 patients with rectal carcinoma have been studied. A curative resection has been carried out in 232. Sphincter-saving procedure was performed whenever possible: the length of margin of resection was at least 2 cm. The operation were: 71 abdominoperineal excisions (AP), 147 anterior resections (AR), 14 transanal excisions. The thirty-days mortality was 7 patients (9.9%) for AP and 5 (3.4%) for AR. Local recurrence was: AP 10 cases (15.6%), AR 16 cases (11.3%); for tumors 4-8 cm from anal verge recurrence was 17.1% for AP, 16.2% for AR. Concerning staging, local recurrence was more common in the Dukes C stage (24.3%) than in the Dukes B (10.2%) or in the Dukes A (3.8%). 5 years survival after AP was 62.2 percent and after AR 67.9 percent. Concluding, in our experience, there was no relationship between local recurrence or survival and type of curative surgery (AP or AR). Local recurrence and survival were only related to tumor stage: lateral tumor extension in these advanced and aggressive lesions appears to be the major determinant of local recurrence. Further investigations are necessary to determine whether the addition of adjuvant radiotherapy or of extended abdomino-iliac lymphadenectomy should be able to improve the results. PMID- 1443991 TI - [Colorectal anastomosis by mechanical suture: a personal technique]. PMID- 1443992 TI - [Trans-suture mechanical colorectal anastomosis in the treatment of rectal cancer. Apropos of 78 cases]. PMID- 1443993 TI - [Usefulness of a colonic reservoir and colo-anal anastomosis after resection for cancer of the 1/3 mid-rectum]. PMID- 1443994 TI - [Role of local excisions in the treatment of rectal cancer]. PMID- 1443995 TI - [Physiopathological changes after interventions for rectal cancer]. PMID- 1443996 TI - [Surgery of liver metastases secondary to colorectal carcinoma]. PMID- 1443997 TI - [Treatment of liver metastases of rectal cancer]. PMID- 1443998 TI - [Adjuvant treatment in rectal cancer]. PMID- 1443999 TI - [Thyroid carcinoma. Criteria for the selection of surgical treatment]. AB - Surgery is still today the first choice treatment in the thyroid neoplasm. The authors examined 37 patients with thyroid cancer out of 389 thyroidal operation performed in the period 1982-85 at the Institute of Surgical Pathology II and Surgical Clinic of University of Bari. The pro-operation screening was scintigraphy, US study and needle biopsy. In 23 case, with positive cytology examination and/or clinical malignancy the performed operation was total extracapsular thyroidectomy. Other nine patients underwent lobectomy and in 2 cases the operation chosen was sub-total strumectomy completed by thyroidectomy after histologically proved malignancy. The laterocervical lymphadenectomy was done only in the case of nodes involvement. Operative mortality was 0 and post operative stay was about 6 days. The extracapsular total thyroidectomy is the first choice operation for cancer. Nevertheless recently some Authors proposed less destructive operation in the small differentiated type cancers with good results. PMID- 1444000 TI - [Use of ceftizoxime in the prevention of postoperative infections]. PMID- 1444001 TI - [Neopterin and interleukin 2 soluble receptors as biochemical markers of cellular immune response to surgical trauma]. AB - In 67 patients submitted to surgical procedures serum neopterin (NPT) and Interleukin 2 soluble receptors (IL2R) were evaluated at the end of the operation as well as 24, 48, 72 hours later. Thirty seven of the subjects (Group B) had undergone minor surgery (average time of operation: 40 +/- 10 min.), thirty (Group A) had undergone major surgery (average time: 180 +/- 30 min.). The results showed elevated NPT and IL2R levels in the latter cases and, in particular, 48 and 72 h after surgery. Neopterin levels were positively correlated with IL2R (r = 0.548 p < 0.01). These data suggest an activation of the cellular immune response which parallels the magnitude and length of surgical trauma. Thus NPT and IL2R levels could represent biochemical markers of postoperative disorders of the immune homeostasis. PMID- 1444002 TI - [Bibliographic information retrieval]. PMID- 1444003 TI - [Lupus pericarditis]. PMID- 1444004 TI - [Rheumatoid pericarditis]. PMID- 1444005 TI - [Interstitial pneumopathies of systemic diseases. Definition and nosology]. PMID- 1444006 TI - [Interstitial pneumopathies of systemic diseases. Clinical aspects]. PMID- 1444007 TI - [Valvulopathies in connectivitis]. PMID- 1444008 TI - [Bronchiolitis obliterans and systemic diseases]. PMID- 1444009 TI - [Apparently primary pulmonary arterial hypertension complicating systemic diseases. Epidemiological survey and review of the literature]. PMID- 1444010 TI - [Pulmonary filariasis: clinical and therapeutic aspects]. PMID- 1444011 TI - [Splenomegaly in a woman who had lived in Africa for 32 years]. PMID- 1444012 TI - [Value of experimental use of praziquantel in cases of isolated cerebral cysticercosis and follow-up of the evolution by MRI]. PMID- 1444013 TI - [Multiple intracranial syphilitic gummas]. PMID- 1444014 TI - [Purulent pericarditis revealing esophageal cancer]. PMID- 1444015 TI - [Bone metastasis of prostatic origin with pseudo-sarcomatous form. Apropos of a case with monomelic localization]. PMID- 1444016 TI - [Medical Society of Paris Hospitals. Medicine as an intellectual model in ancient Greece]. PMID- 1444017 TI - Beyond deficiency. New views on the function and health effects of vitamins. Introduction. PMID- 1444018 TI - Role of nutrients in delaying cataracts. PMID- 1444019 TI - Influence of vitamins E and B6 on immune response. PMID- 1444020 TI - Antioxidant vitamins and prevention of lung disease. AB - Although the evidence for oxidative stress for air pollution in the human lung is fragmentary, the hypothesis that oxidative stress is an important, if not the sole, mechanism of toxicity of oxidizing air pollutants and tobacco smoke is compelling and growing. First, biochemical mechanisms have been worked out for oxidation of lung lipids by the gas phase of cigarette smoke, NO2 and O3. The oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is more effective in preventing oxidation by NO2, and vitamin E is more effective against O3. Second, multiple species of experimental animals develop lung disease similar to human bronchitis and emphysema from exposure to NO2 and O3, respectively. The development of these diseases occurs over a near lifetime exposure when the levels of NO2 or O3 are at near ambient air pollution values. Third, isolated human cells are protected against oxidative damage from NO2 and O3 by both vitamins C and E. Fourth, the vitamin C level in the lung either declines on exposure to NO2 for short-term exposures or increases on chronic cigarette smoke exposure. The effects of cigarette smoking on serum vitamin C is apparently complex and may be related to the daily intake of vitamin C as well as smoking. Serum vitamin C levels may be poor indicators of lung demands when daily vitamin C intakes are above 100 mg/day. Fifth, vitamin C supplementation protects against the effects of ambient levels of air pollution in adults as measured by histamine challenge. An augmented response to histamine challenge may represent increased lung permeability brought about by air pollution. In experimental animal and human experiments, the amount of vitamin C or E that afforded protection was in excess of the current recommended dietary allowance. Although animal studies do not provide evidence for complete protection against NO2 or O3, they do illustrate that current recommended daily allowances are inadequate for maximum protection against air pollution levels to which over 100 million Americans are exposed. The problem of air pollution and its effects on humans is truly of global concern. Air pollution is not restricted to North America or Japan where it was first recognized, but is a major public health problem in Europe as well. When data are available, air pollution probably will be shown to be a major public health problem in all urban areas of the world.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1444021 TI - Effects of drugs on vitamin needs. PMID- 1444022 TI - Influence of HIV infection on vitamin status and requirements. PMID- 1444023 TI - Effect of vitamin C on transient increase of bronchial responsiveness in conditions affecting the airways. PMID- 1444024 TI - Measles-induced vitamin A deficiency. PMID- 1444025 TI - The effects of vitamins B12, B6, and folate on blood homocysteine levels. AB - The interaction between plasma homocysteine levels and vitamins B6, B12, and folate is an exciting field and one that has gathered great momentum over the past few years, with the recognition that homocysteine probably plays an important role in occlusive vascular disease. Our understanding in this field is greatly advanced compared to just a few years ago. There are a number of important issues, however, that will need to be addressed in the future if we are to develop a sufficient knowledge base to effectively minimize the risk of occlusive vascular disease ascribable to hyperhomocysteinemia. These include (1) definitive evidence that homocysteine is the actual agent that mediates accelerated occlusive vascular disease and the mechanism by which this occurs; (2) an understanding of what constitutes a pathologic elevation in homocysteine (is there a threshold concentration in the plasma below which no vascular injury occurs? is the peak concentration achieved the critical determinant of injury, or is the area under the curve, or some other feature, more important?); (3) understanding what synergies might exist by adding B6 or B12 to a regimen of folate supplementation (what doses are most appropriate? will toxologic issues limit the utility of supplementation?); and (4) determining the circumstances where reduction of plasma homocysteine will retard or reverse the process of occlusive vascular disease. PMID- 1444026 TI - Relationship of vitamin C status to cholesterol and blood pressure. PMID- 1444027 TI - Physiological importance of extra-hepatic vitamin K-dependent carboxylation reactions. PMID- 1444028 TI - Ischemia: reperfusion injury and restenosis after coronary angioplasty. AB - Percutaneous transluminal coronary angioplasty (PTCA) is a very effective technology that allows, without surgery, successful mechanical revascularization of acutely or chronically obstructed coronary arteries. The success of PTCA in patients with acute myocardial infarction or unstable angina is questioned by early coronary reocclusion and by so-called reperfusion injury. In a biochemical context, reperfusion injury occurs as a very complex interaction between the different tissues that build heart muscle. Free radicals play a pivotal role and initiate a deleterious cascade of events after reperfusion. Protective mechanisms such as superoxide dismutase, glutathione peroxidase, and catalase are normally present in the cell to prevent damage by free radicals. Endothelial cells have a greater number of specific physiologic and metabolic functions and influence the microcirculatory flow. In the presence of exogenous glucose, coronary endothelial cells show a pronounced lactate production under well-oxygenated conditions. Low energy demand and high glycolytic activity may be the cause of why the coronary endothelium is less severely injured than the cardiomyocytes in the ischemic and anoxic heart. The success of PTCA in patients with chronically obstructed coronary arteries (stable angina) is questioned by vessel occlusion and restenosis. Restenosis is a very complex process involving clinical, morphological, procedural, regional flow-dependent, and biological determinants. Early platelet deposition, formation of mural thrombus, coronary vasospasm, and elastic recoil forces of stretched vessel wall may contribute to early restenosis in the first days after PTCA, but the peak incidence of restenosis occurs between two and three months after PTCA. Intimal hyperplasia or proliferation of smooth muscle cells is believed to be the fundamental process of restenosis. To solve the problem of restenosis, much effort has been expended, which includes several technical and pharmacological approaches. Pharmacological strategies, systemically or locally administered, aim at increased vasomotor tone, platelet function, smooth muscle cell proliferation/migration, and fibrocollagenous healing. Up to now none of the proposed drugs has been able to reduce the restenosis rate. There is experimental evidence for a claim that the antioxidant functions of vitamins (E, C, and beta-carotene) may prevent restenosis post-PTCA. Until recently, in most post-PTCA restenosis trials the angiographic analyses were not performed using computerized measurement methods. In order to assess the efficacy of acute or long-term interventions on the natural course or acute complications of coronary artery disease, quantitative measures have been introduced and validated that make use of digital coronary angiography and computerized image processing techniques.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1444029 TI - Influence of antioxidant vitamins on LDL oxidation. PMID- 1444030 TI - Dietary antioxidants and cardiovascular disease. PMID- 1444031 TI - Potential role of beta-carotene and antioxidant vitamins in the prevention of oral cancer. PMID- 1444032 TI - Vitamin E and cancer: epidemiology. PMID- 1444033 TI - Vitamin C status and cancer. Epidemiologic evidence of reduced risk. PMID- 1444034 TI - Safety issues regarding the use of vitamin supplements. PMID- 1444035 TI - Interaction of riboflavin with zinc bioavailability. PMID- 1444036 TI - Effect of short-term feeding of barley oil extract containing naturally occurring tocotrienols on the immune response of rats. PMID- 1444037 TI - Qualitative relationship of dietary and plasma carotenoids in human beings. PMID- 1444038 TI - Omega-3 fatty acid supplementation stimulates alpha-tocopherol incorporation in erythrocyte membranes in adult men. PMID- 1444039 TI - Biochemical, morphological, and functional aspects of systemic and local vitamin A deficiency in the respiratory tract. PMID- 1444040 TI - Crystalloid lysozyme inclusions in Paneth cells of vitamin A-deficient rats. PMID- 1444041 TI - The influence of antioxidants on the enhanced respiratory burst reaction in smokers. PMID- 1444042 TI - Vitamin B6. Reservoirs, receptors, and red-cell reactions. PMID- 1444043 TI - Ascorbic acid supplements and blood pressure. A four-week pilot study. PMID- 1444045 TI - Psychological disorders as early symptoms of a mild-to-moderate vitamin deficiency. PMID- 1444044 TI - The hematological and electrophysiological effects of cobalamin. Deficiency secondary to vegetarian diets. PMID- 1444046 TI - Vitamin E and skeletal muscle contracture in vitro. PMID- 1444047 TI - Plasma folate adequacy as determined by homocysteine level. PMID- 1444048 TI - Antioxidant response to exercise-induced oxidative stress and protection by vitamin E. PMID- 1444049 TI - Antioxidant status and free radical-induced oxidative damage of sickle erythrocytes. PMID- 1444050 TI - Vitamin E inhibits the carcinogenicity of N-nitrosomethylbenzylamine. PMID- 1444051 TI - Folate status and pregnancy outcome. PMID- 1444052 TI - The relation between low-fat intake and vitamin status in a free-living cohort of preschoolers. PMID- 1444053 TI - Dietary vitamin B6 and vitamin C. Influence on immune response and disease resistance in Atlantic salmon (Salmo salar). PMID- 1444054 TI - Ascorbic acid bioavailability in humans. Ascorbic acid in plasma, serum, and urine. PMID- 1444055 TI - Effects of supplemental vitamin E on cancer growth and promotion during murine AIDS. PMID- 1444056 TI - Effects of antioxidant vitamins C, E, and beta-carotene on immune functions in MRL/lpr mice and rats. PMID- 1444057 TI - Selective biodiscrimination of alpha-tocopherol stereoisomers. Similar enrichment of all 2R forms in rat tissues after oral all-rac-alpha-tocopheryl acetate. PMID- 1444058 TI - Vitamin E prevents side effects of high doses of vitamin A in chicks. PMID- 1444059 TI - Regulatory role of oxidized and reduced pteroylpolyglutamates. PMID- 1444060 TI - Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. AB - Tocopherols and tocotrienols (vitamin E) and ascorbic acid (vitamin C) as well as the carotenoids react with free radicals, notably peroxyl radicals, and with singlet molecular oxygen (1O2), this being the basis of their function as antioxidants. RRR-alpha-tocopherol is the major peroxyl radical scavenger in biological lipid phases such as membranes or low-density lipoproteins (LDL). L Ascorbate is present in aqueous compartments (e.g. cytosol, plasma, and other body fluids) and can reduce the tocopheroxyl radical; it also has a number of metabolically important cofactor functions in enzyme reactions, notably hydroxylations. Upon oxidation, these micronutrients need to be regenerated in the biological setting, hence the need for further coupling to nonradical reducing systems such as glutathione/glutathione disulfide, dihydrolipoate/lipoate, or NADPH/NADP+ and NADH/NAD+. Carotenoids, notably beta carotene and lycopene as well as oxycarotenoids (e.g. zeaxanthin and lutein), exert antioxidant functions in lipid phases by free-radical or 1O2 quenching. There are pronounced differences in tissue carotenoid patterns, extending also to the distribution between the all-trans and various cis isomers of the respective carotenoids. Antioxidant functions are associated with lowering DNA damage, malignant transformation, and other parameters of cell damage in vitro as well as epidemiologically with lowered incidence of certain types of cancer and degenerative diseases, such as ischemic heart disease and cataract. They are of importance in the process of aging. Reactive oxygen species occur in tissues and cells and can damage DNA, proteins, carbohydrates, and lipids. These potentially deleterious reactions are controlled in part by antioxidants that eliminate prooxidants and scavenge free radicals. Their ability as antioxidants to quench radicals and 1O2 may explain some anticancer properties of the carotenoids independent of their provitamin A activity, but other functions may play a role as well. Tocopherols are the most abundant and efficient scavengers of peroxyl radicals in biological membranes. The water-soluble antioxidant vitamin C can reduce tocopheroxyl radicals directly or indirectly and thus support the antioxidant activity of vitamin E; such functions can be performed also by other appropriate reducing compounds such as glutathione (GSH) or dihydrolipoate. The biological efficacy of the antioxidants is also determined by their biokinetics. PMID- 1444061 TI - Localized deficiencies of folic acid in aerodigestive tissues. AB - The notion that requirements for folic acid may be higher in some tissues than others, resulting in localized deficiencies in spite of blood levels in the normal range was first suggested by the observation of megaloblastic changes in the cervical epithelium that responded to folate supplementation. Theoretically, such deficiencies may arise from elevated folate turnover in response to rapid tissue proliferation or repair; inactivation or alteration of its function by external agents such as tobacco, alcohol, or drugs; or altered metabolism or tissue uptake caused by an inborn error. Marginal dietary intake could aggravate these effects on cells at risk. Evidence for the possible existence of localized folate deficiencies in the aerodigestive tract includes lower circulating folate levels in smokers as compared with nonsmokers; yet lower circulating levels in smokers with bronchial metaplasia; lower folate levels in scrapings of the buccal mucosa of smokers than non-smokers; apparent improvement in bronchial atypical metaplasia in smokers supplemented with folic acid; lower erythrocyte folate levels and higher prevalence of cellular features compatible with folate deficiency in geographic areas and individuals in South Africa at high risk for esophageal cancer; and a trend toward a lower prevalence of colonic dysplasia in ulcerative colitis patients who use folic acid supplements. These observations, as well as animal and in vitro studies, also suggest that folate deficiency may be co-carcinogenic. Further research in this area will be aided by the development of animal models of localized folate deficiency and of methodologies capable of measuring folate levels in minute quantities of tissues and exfoliated cells. PMID- 1444062 TI - Vitamin E. Neurochemistry and implications for neurodegeneration in Parkinson's disease. AB - Recently there has been a great deal of interest in the potential therapeutic use of supplemental vitamin E in amelioration of diseases of the nervous system. Even though many studies have provided encouraging results, the mechanism of any beneficial effect remains elusive. Experimental studies suggest that the presence of high levels of vitamin E in tissues prior to injury is essential for biological efficacy because administration of the vitamin after insult is often ineffective. The rationale for this phenomenon is unknown at present. Some of the remaining areas of investigation include the biochemical interaction of vitamin E with other biological antioxidant substances such as vitamin C and sulfhydryl compounds; the relative potencies of different molecular forms of tocopherols, such as trienols and various optical isomers; and the optimal dosage and mode of administration of the most potent tocopherol molecule. Future research on these and other topics will shed more light on the effective use of vitamin E in neurodegeneration. PMID- 1444063 TI - A study of the performance and comparability of the sampling response to cotton dust of work area and personal sampling techniques. AB - In order to compare and contrast the sampling response to cotton dust of two forms of dust sampling 85 work areas were identified over a 2-year period for investigation in eight Lancashire spinning mills. Three hundred and five work area dust samples were undertaken and 252 personal dust samples were performed. Operatives who spent a minimum of 80% of their working shift in the area in which work area sampling was also performed were selected for personal sampling. Work area dust exposures have recently shown an upward trend, with highest concentrations occurring in the ring spinning room (median 1.15 mg m-3, range 0.82-2.06). Personal dust samples showed a reduction in dust exposures as cotton processing progressed, from a high in the opening room (median value of 6.24 mg m 3, range 1.0-41.5) to a minimum of 1.02 mg m-3 (range 0.30-0.93) in the winding room. The ratio of measured personal sampling dust exposure to work area sampling exposure was used to compare the relative performance of the two techniques. This ratio was highest in the early processes. There was a 7.8-fold difference in measurement between the two techniques in the opening processes, falling to 4.9 in carding and 4.2 in the other card-room processes. However in ring spinning the ratio was only 1.4, suggesting a degree of comparability in the methods at this stage of processing. The value rose to 2.5 for the last stage (winding). Respiratory disease is known to occur predominantly in the early stages of processing (opening and carding) where high dust concentrations are found using the personal technique. These data support the use of personal sampling for setting exposure limits to cotton dust in preference to the current recommended method using work area sampling techniques, which may significantly underestimate dust exposure in the high risk work areas and is outdated. PMID- 1444064 TI - Occupational exposure to carbon monoxide and sulphur dioxide during the manufacture of carbon black. AB - The manufacture of carbon black is known to generate carbon monoxide and sulphur dioxide in the 'production gas' and the pyrolysis products of the 'production gas', respectively. Adverse health effects have been reported as associated with both contaminants (coronary heart disease with carbon monoxide and respiratory morbidity with sulphur dioxide). A major cross-sectional and longitudinal respiratory morbidity study is being conducted to assess the effects of exposure to carbon black on lung function, on chest X-rays and on responses to a questionnaire. The questionnaire includes questions on respiratory and cardiovascular symptoms, so that information regarding confounding exposure is essential. The working population of 18 manufacturing plants in seven European Countries was split into 13 job title numbers (1-13) which were then amalgamated into five job categories (A-E), with an appropriate (statistically) number of samples taken from each plant-job category. In total, 1322 carbon monoxide samples and 1301 sulphur dioxide samples were taken, using actively pumped longterm colorimetric tubes. In the majority of cases, more than half of the samples in each plant-job category were either zero or trace, thereby preventing the accurate estimation of the average exposure. The highest median carbon monoxide concentration was from the amalgamated data from all 18 plants in job number 9 (furnace operators), the highest median sulphur dioxide concentration was only 'trace'. The large number of zero and trace values also precluded the generation of current and retrospective exposure indices. PMID- 1444065 TI - Assessment of dermal and inhalation exposure to zineb/maneb in the cultivation of flower bulbs. AB - In bulb farming the use of pesticides for crop protection and bulb disinfection is extensive. To estimate long-term occupational exposure to pesticides, generic levels of exposure specific to the method of working were needed. In order to derive these values, dermal and inhalation exposure to the fungicide mixture zineb/maneb was assessed for different methods of mixing and loading a wettable powder formulation. Further, dermal exposure was also assessed for two methods of disinfection of bulbs. Observed exposure was expressed in terms of method specific levels of exposure, which makes it possible to compare exposure resulting from different methods of working, with respect to the amount of pesticide handled, or whether ladling the pesticide with a scoop or dipping the bulbs using baskets resulted in high exposure. Moreover, the relative importance of dermal and inhalation exposure routes was estimated. The results show that during mixing and loading with bare hands dermal exposure is by far the greater contributor (greater than 99%) to the total estimated exposure. Comparing these results and also some preliminary results of the dermal protection provided by working gloves, with tentative health-based limit values of exposure, emphasize the need for a programme on appropriate dermal protection. PMID- 1444066 TI - Solvent exposure and related work practices amongst apprentice spray painters in automotive body repair workshops. AB - As part of a multidisciplinary study into the health effects of solvents, workplace assessments and airborne solvent vapour monitoring was conducted in 46 spray painting workshops in the Sydney metropolitan area. Breathing-zone samples were taken from 50 apprentices and 14 experienced spray painters. An interview schedule was developed to obtain information about the use of acrylic or two-pack paint systems, the use of engineering controls, the use of personal protective equipment and the availability of material safety data sheets. Contaminants typical of the chemical products used in this industry were encountered (aromatic hydrocarbons, C5-C7 aliphatic hydrocarbons, ketones, esters). The results of airborne solvent monitoring indicate a total solvent exposure in the range 1-99% of a combined Worksafe Australia exposure standard, with a mean of 19%. Solvent exposure was highest when spraying acrylic paint in the open workshop and lowest when spraying two pack paint in a spray booth. Much the same personal protective equipment was available in all workshops, but wide variation in its use was observed. Material safety data sheets were not observed in any of the workshops. PMID- 1444067 TI - A pilot study to evaluate Japanese standard radiographs of pneumoconioses (1982) according to the ILO 1980 International Classification of Radiographs of Pneumoconioses. AB - The Japanese Classification of Radiographs of Pneumoconioses (JC) is characterized by its own standard films, including limit films which are defined to represent the upper limit of category 0 or the lower limit of category 1. This pilot study was aimed at evaluating the JC standard radiographs according to the ILO 1980 International Classification of Radiographs of Pneumoconioses (IC) in which some of the JC standards were read according to the IC by two groups of experienced British workers, four non-medically qualified (NM panel) and six medically qualified (MQ panel). The Japanese standard limit films, with rounded opacities of category 0/1 or 1/0, were classified by both groups as having lower categories in the IC than in the JC. With the standard mid-category films showing rounded or irregular opacities, the NM panel tended to produce higher categories than the MQ panel. From reading results by both panels, however, it may be said that the JC mid-category standards agree with the IC in terms of category. PMID- 1444068 TI - Occupational exposure to carbon black in its manufacture. AB - Carbon black is manufactured by the vapour phase pyrolysis of heavy aromatic hydrocarbon feedstocks. Its manufacture is worldwide and the majority of its production is for use in the rubber industry especially tyre manufacture. Its carbonaceous nature has led many to investigate the occurrence of exposure related medical conditions. To quantify any such relationships, it is necessary to assess exposure accurately. As part of such an epidemiological investigation survey involving the measurement both of respirable and of total inhalable carbon black was undertaken in 18 plants in seven European countries between mid-1987 and mid-1989. A total of 1298 respirable samples (SIMPEDS cyclone) and 1317 total inhalable samples (IOM head) were taken and deemed of sufficient quality for inclusion in the study. The distributions of the time-weighted average values were assessed and found to be best described by a log-normal distribution, and so exposure is characterized by geometric means and standard deviations. The data are presented in terms of 13 separate job titles for both dust fractions and shows a wide variation between job titles, with the highest mean exposure experienced by the site cleaners, and 30% of the samples taken from the warehouse packers being in excess of the relevant countries' occupational exposure limits for total inhalable dust. The quality and extent of this data allows both for comparison with exposure standards and for generation of occupational exposure indices, which will be presented in another paper (Gardiner et al., in preparation). PMID- 1444069 TI - Determination of exposure to cobalt and nickel in the atmosphere in the hard metal industry. AB - Cobalt and nickel, matrices of hard metal, have been shown to be respiratory sensitizers. Airborne dust at hard metal-grinding worksites in a factor with a work-force of about 180 grinders was analysed for cobalt and nickel. The electron microscopic X-ray microanalysis of airborne dust particles demonstrated that they had the same metallic components as hard metal products. Andersen sampling revealed that 66% of total dust was respirable (< 7 microns). Consecutive personal sampling for individuals indicated log-normally distributed concentrations of total dust and cobalt. Of the workers surveyed, 12% (16 out of 133) were exposed to cobalt at more than 50 micrograms m-3, while 1.5% (two out of 133) were exposed to nickel concentrations of more than 50 micrograms m-3. A correlation between cobalt exposure concentrations and nickel concentrations for individuals was significant and positive. Further improvement of the working environment is necessary because of the hazard caused by exposure to cobalt and nickel. PMID- 1444070 TI - Occupational exposure to chromium, copper and arsenic during work with impregnated wood in joinery shops. AB - CCA-impregnated timber contains copper, chromium and arsenic (CCA), and occupational exposure to wood dust as well as the CCA compounds may occur in work with such timber. Dust from commercially available impregnated wood has been found to contain hexavalent chromium, which is regarded as a carcinogen. Apart from determinations of the total amounts of the CCA compounds, specific determination of hexavalent chromium is therefore essential. Selective methods have been applied for control of the work environment in six joinery shops. The mean exposure to wood dust was found to be below 1 mg m-3. The mean airborne concentration of arsenic around various types of joinery machines was in the range from 0.54 to 3.1 micrograms m-3. No hexavalent chromium was detected in any samples and no increased concentrations of arsenic were found in urine from the workers. The presence of arsenic in the work-room air must be considered for appropriate assessment of the occupational environment in joinery shops. PMID- 1444071 TI - Pulmonary clearance of fibrous and angular SiC particulates in the sheep model of pneumoconiosis. AB - Both angular and fibrous SiC (carborundum) particulates can be emitted by SiC production operations. Carborundum pneumoconiosis is now recognized as an occupational lung disease with specific pathological features. These were previously reproduced in the sheep model of pneumoconiosis with fibrous SiC but not with angular SiC. To further document this question, the pulmonary retention in the sheep of the two morphological types was studied. Animals were injected in the tracheal lobe with equal mass (100 mg) of particulates prepared from SiC materials taken in the field. Particles were measured by analytical transmission electron microscopy in samples of bronchoalveolar lavage fluids (BAL) obtained at months 2, 4, 6 and 8 after the injection. They were also measured in samples of lung parenchyma obtained at month 8. Measurements in BAL and in lung samples both indicated a much lower retention for fibrous than for angular SiC. The retention rate in lung parenchyma at month 8 was 30 times lower for fibrous SiC. The half life of decrease of concentrations was 3.4 times shorter for fibrous SiC. Other data in the literature support the notion that fine fibres are cleared more effectively than coarser angular particles. PMID- 1444072 TI - Clinical results of glaucoma surgery using the White glaucoma pump shunt. AB - The findings are reported in 37 patients with refractory glaucoma who were treated with the White glaucoma pump shunt for 6 months to 2 years (average follow-up, 14 months). Thirty-three patients (89%) had an intraocular pressure 22mmHg after six months and beyond, with or without medications. The decrease in intraocular pressure ranged from 24 to 33mmHg. Visual acuity improved in 12 patients, remained the same in 18 patients, and decreased in seven patients (all decreases were caused by progression of unrelated ocular disease). PMID- 1444073 TI - Biometric aspects of diffractive multifocal intraocular lenses. AB - A retrospective biometric study was done on 132 patients with diffractive multifocal intraocular lenses. The two principal focal points induced by the intraocular lens were refracted for distance in each patient. The difference in diopters between the refractions was obtained, and the A constant (SRK formula series) and anterior chamber depth (ACD, Binkhorst formula) were calculated. Our results showed the A constant was 116.46. This value was consistent and not affected by the axial length of the eye in the 22mm to 24.5mm range. In patients who had emmetropia with the intraocular lens power implanted alone, the constant was equal to 116.3. The ACD was 3.94mm. This value was lower in shorter eyes and higher than 3.94mm in longer eyes. On the basis of the data obtained, when the SRK-II formula is used, an A constant of 116.4 should be used in preoperative biometric calculations. PMID- 1444074 TI - Bilateral inferotemporal dialysis in identical twins. AB - Retinal detachment associated with inferotemporal dialysis comprises approximately 10% of all retinal detachments. We describe the cases of two patients with bilateral inferotemporal dialyses who were identical twins. This finding suggests that genetic factors play a role in some cases of inferotemporal dialysis. One of the twins was asymptomatic, stressing the importance of examining other family members of patients with nontraumatic retinal dialysis. We believe that the cause of inferotemporal dialysis is multifactorial and there is a definite subpopulation in which a genetic predisposition is present. PMID- 1444075 TI - Idiopathic preretinal macular gliosis: a retrospective study of 200 patients. AB - The charts of the last 200 patients with idiopathic preretinal macular gliosis (IPRMG) seen in the Retina Service of Montefiore Medical Center, Albert Einstein College of Medicine, were reviewed. We found that IPRMG is a disease of older people, tends to have a nonprogressive course, and rarely causes severe visual loss. In our series, 91.5% of the patients were older than 50 years of age, 80% of eyes lost less than two lines of vision, and only 4% of eyes had a visual acuity 20/200. PMID- 1444076 TI - Trabeculectomy with 5-fluorouracil subsequent to circular buckling operation and cataract extraction. AB - Six patients, each with one eye that had previously undergone circular buckling surgery for the repair of retinal detachment before or followed by cataract extraction with or without intraocular lens implantation, underwent trabeculectomy with 5-fluorouracil (5-FU) for intractable glaucoma. Surgery was done through scarred subconjunctival tissues that were excised partially. The total doses of 5-FU ranged from 65 to 100mg (mean +/- standard deviation, 84.2 +/ 13.2mg) Eight to 47 months later, intraocular pressures were 18mmHg in five eyes, two of which were not receiving hypotensive medications. In the sixth eye, the intraocular pressure was 26mmHg with maximum hypotensive treatment. Intraocular pressures in the six eyes were significantly lower postoperatively than preoperatively (P < .05). This preliminary study suggests that filtering surgery with 5-FU may be beneficial after intraocular operations even in eyes where it is done through postoperative scarred subconjunctival tissues. PMID- 1444077 TI - False-positive magnetic resonance imaging of a metastatic carcinoma simulating a malignant melanoma. AB - Previous studies have shown the value of magnetic resonance imaging (MRI) in the diagnosis of malignant melanoma of the choroid. We describe the case of a patient with a choroidal mass whose MRI study was characteristic of malignant melanoma. Subsequently the eye was enucleated. However, on histopathologic examination, the mass was a metastatic carcinoma to the choroid. This false-positive study makes us question the value of MRI in the diagnosis of malignant melanoma of the choroid. PMID- 1444078 TI - Radiotherapy resolves leukemic involvement of the optic nerves. AB - A 40-year-old woman with acute lymphoblastic leukemia had a visual disturbance OD. The optic disc was slightly swollen in the right fundus, and blast cells in the cerebrospinal fluid were found. Radiotherapy to the brain and orbit resolved these findings. Five months later, visual acuity decreased OS. Radiotherapy also was effective in treating the leukemic involvement of the optic nerve. PMID- 1444079 TI - Farnsworth-Munsell 100-hue test for patients with diabetes mellitus. AB - We evaluated 164 eyes of 87 patients with diabetes mellitus compared with 50 eyes from 25 healthy subjects as the control group. We compared 87 patients with diabetes mellitus (164 eyes) in relation to their duration of diabetes, fundus findings, visual acuity, and color vision defects. In all patients, color vision defects were determined using the Farnsworth-Munsell 100-hue test, and the total error score was established on the basis of age norms from subjects without diabetes. No color vision defect was detected in the control group. In the diabetic group, fundus degeneration and color vision defects were observed and correlated with the duration of diabetes. The dominant color defect was of the blue-yellow type. PMID- 1444080 TI - Typical ocular coloboma affects three generations in one family. AB - We found bilateral colobomas of the iris, choroid, retina, and optic nerve head in a son, mother, and grandmother in one pedigree. This represents a rare incidence of typical ocular coloboma in three generations. PMID- 1444081 TI - Sneezing as a cause of acute angle-closure glaucoma. AB - We report the case of a patient who had an attack of acute angle-closure glaucoma precipitated by sneezing, probably as a result of a sudden increase in venous back pressure. This young woman had a history of allergic sinusitis. PMID- 1444082 TI - New applications of the neodymium: yttrium aluminum garnet laser in the Q switched mode: experimental results. AB - We describe the interaction of the neodymium: yttrium aluminum garnet (Nd:YAG) laser energy with intraocular lenses using the laser in the Q-switched mode. Using this method, it is possible to treat opacities that eventually might occur at the level of the visual axis on the optic faces of polymethylmethacrylate intraocular lenses (IOLs) if safety parameters (perfect focusing, use of additional lenses, and slight and continuous movement of the focal point of the laser) are followed. However, it is not possible to treat the silicone IOLs with the Nd:YAG laser because the threshold values for damage to the IOL are lower than the energy values required for destroying the capsular opacities on the optic axis. PMID- 1444083 TI - Atropine after trabeculectomy. AB - Thirty-eight patients requiring trabeculectomy for control of open-angle glaucoma were randomized into two groups. One group received topical atropine immediately after trabeculectomy; the second group began treatment on the first postoperative day. The two groups were compared over the first three postoperative days. The theoretic benefit of atropine instillation immediately after trabeculectomy is discussed. Our results showed no significant difference between the two groups except there was a significantly larger pupil diameter in the treated group on the first postoperative day. PMID- 1444084 TI - Digital fundus imaging of subretinal neovascularization. AB - Digital fundus imaging was used for fluorescein angiography in patients with subretinal neovascularization. After laser treatment, digital red-free photographs were obtained and compared against pretreatment angiogram frames to determine the margins of treatment. This technique allowed instant review of images and confirmation of complete laser treatment of the lesions. Of 15 eyes treated and followed for at least one year, there were two eyes with early recurrences (13%). A total of five eyes had recurrences during the follow-up period (33%). Digital imaging is a useful tool for treating subretinal neovascularization. PMID- 1444085 TI - Endothelin does not affect experimentally induced corneal neovascularization. AB - Endothelin, a potent vasoconstrictor, was found to be ineffective in the treatment of experimentally induced corneal neovascularization. Endothelin was administered topically, subconjunctivally, and intraluminally in serial concentrations ranging from 0.0005 to 5.0 micrograms/mL in New Zealand white rabbits without effect. Electron microscopy of the neovascular cornea revealed the vessels consisted only of endothelin and pericytes. Hence, the vessels were not responsive to endothelin because they lacked contractile smooth muscle. PMID- 1444086 TI - [Reduction laryngoplasty by external approach for glottic incompetence. Current role, demonstration of its efficacy by objective analysis of parameters of vocal quality]. AB - Authors talk about the place of surgical treatments with cervicotomy in abducted vocal cord, about the statistics of the department of Phoniatrics of the Hospital Edouard Herriot in Lyon. These techniques have actually a marginal place. But the analysis of a recent case shows us that endoscopic treatment for vocal fold augmentation with biomaterials such as collagen or teflon can fail. So ENT surgeons have to absolutely know the Guerrier's technique to improve the quality of the voice when injectable biomaterials fail. With the description of this case, we will describe the objective analysis methods of the voice parameters that we use in the department. PMID- 1444087 TI - [Reconstruction of the mandibular arch using free vascularized iliac and scapular grafts. Arguments in favor of using scapular grafts]. AB - In 12 cases of surgically removed mandibular symphysis malignancies, the bone and mouth floor were reconstructed using osteo-musculocutaneous flaps from the iliac crest or free osteo-cutaneous scapular flaps. In our experience, the latter provide the best results. Removed in dorsal decubitus, they allow floor replacement. During the dissection of the tumor site, we also preserve labial and clin structures, which favours a good restoration of phonation and swallowing. PMID- 1444088 TI - [Long-term esophageal and oropharyngeal pH-metry in ORL manifestations of gastroesophageal reflux in children]. AB - Several studies published over the last few years have pointed out the importance of gastroesophageal reflux (GER) in the pathogenesis of certain cases of chronic or recurrent pharyngo-laryngitis. While the presence of an acid reflux at the level of the pharyngo-larynx has recently been demonstrated in certain cases, the real incidence and pathogenic impact of this reflux is not precisely known. A new technique of continuous 24 hour bi-level monitoring of endoluminal pH in the esophagus and the oro/hypopharynx has made it possible to observe the variations in acid-base balance in contact with the pathological mucosa. 21 patients, 2 months to 7.5 years old, presenting recurrent episodes of pharyngitis or laryngitis, underwent continuous pH monitoring during a 24 hour hospitalization. 6 control subjects, 1 month to 13 years old, presenting no chronic or recurrent ear, head or neck pathology and no sign or symptom of GER were subjected to the same monitoring regimen. A statistically significant difference between the 2 groups is evident for most of the parameters analysed. The most discriminative parameter is the fraction of the total recording time where the pharyngeal readings remain under ph6 (p < 0.0005). These results demonstrate that, in this clinical condition, acid of gastroesophageal origin is in contact with the pharyngeal mucosa. This suggests that the acid has a causal role in the pathological changes observed in the pharyngolaryngeal mucosa. PMID- 1444089 TI - [Exposure of the facial recess through the ear canal. Value in posterosuperior retraction pockets (initial results)]. AB - 19 patients had surgery for progressive [17] and/or symptomatic [2] posterior attic retraction pockets involving the facial recess. Exposition of the suprapyramidal region was obtained after endaural incision by thinning the posterior wall of the ear canal and removing the posterior-superior portion of the tympanic sulcus. This technique is less complicated than intact canal wall tympanoplasty with mastoidectomy. Yet gives similar functional results. After a mean follow-up of 20.3 months, we have observed no residual cholesteatoma and no recurrent retraction pockets. Unlike posterior tympanoplasty, this technique makes it possible to meticulously remove the osteitic bone invariably found in the facial recess when there is infection of the retraction pocket. PMID- 1444090 TI - [Improvement of clinical results by digitalization of a single channel cochlear implant]. AB - For 1973 we have been among the first to claim the multichannel cochlear implant superiority regarding single channel efficacy. However we actually thing that single channel cochlear implant is indispensable in case of total ossified cochlea, and very useful when efficacy/coast ratio must be considered. In order to narrow the gap between multi and single channel device efficacy, we used the new microprocessors possibilities to digitalize the analogic emietter of the single channel system, which we designed in 1987. Owing to a PC keyboard the new emietter allows the speech therapist to select the frequency band width of the input signal, and to determine the threshold level and the dynamic value as a function of six steps values of the stimulus wave frequency. These improvements supply the patient with a better speech intelligibility excepted for vowels discrimination. Comparison of clinical results obtained through the two analogic and digital systems are reported on 4 post lingually and 4 pre lingually deaf patients. PMID- 1444091 TI - [Indications and results of cochlear implants in young children]. AB - In order to determine the criteria for patient selection and the preoperative prognostic factors for hearing recovery after cochlear implants in young totally dead children, the results of hearing rehabilitation were studied in 15 children who had undergone cochlear implantation at from 2 to 9 years of age. The choice of implant is determined by the permeability of the cochlear duct. A multi-system should be used, except when the cochlea is totally ossified. The reliability and efficacy of mono and multi system implants make it possible to offer a solution to the urgent therapeutic problems posed by total deafness in the young child. PMID- 1444092 TI - [Value and control possibilities of the vertebral artery in tumor surgery at the base of the skull]. AB - Following anatomical description of the third segment of the vertebral artery (from C2 to the foramen magnum), the surgical techniques which permit to expose and control this artery at this level are presented. Choice is between the posterior approach in sitting or procubitus position and the lateral approach in supine position. The former is mainly applied on intradural tumors or prolongments and the latter on extradural tumors. These techniques were utilized on more than 60 cases including for the most frequent types meningiomas, neurinomas, paragangliomas and osseous tumors and were associated with a very low morbidity and mortality. PMID- 1444093 TI - [Local immunologic system of the nose and paranasal sinuses]. AB - The mucus membranes of the nasal chambers may be compared to a local immune system which has been called the NALT. The submucosa contains a lymphoid infiltration of T-helpers, T-suppressors and a set of plasma cells capable of synthetizing four IgG subgroups, IgM, IgA and IgD. The IgA plasma cells are most numerous. There is no local synthesis of IgE. Macrophages and langerhans' giant cells are present. The epithelium is an immunological entity which is composed, in addition to secretory cells, of uliated cells, lymphocytes, and M cells. The epithelium is able to synthesize secretory component and allows the transport of IgA and IgM into the secretions. The NALT has multiple immunological functions: antigenic information, humoral immune response, and expression of local cellular immunity. Modifications in T lymphocyte subpopulations are observed in allergic rhinitis. Secreted interleukins modify the local efflux and affluence of effector cells (mastocytes and eosinophils). Abnormalities of the NALT are characteristic of deficiency in humoral IgA and IgG subgroups. The possible presence of alterations of cellular immunity in chronic rhinosinusitis has been suggested. PMID- 1444094 TI - Point-touch technique of botulinum toxin injection for the treatment of spasmodic dysphonia. AB - Intralaryngeal injections of botulinum toxin (Botox), under electromyographic guidance, have emerged as an effective treatment for adductor spasmodic dysphonia. To remain effective, these injections must be repeated every 3 to 9 months as the symptoms recur. One drawback to the current method is the need for electromyographic confirmation of needle placement into the thyroarytenoid muscle. This report describes an anatomic approach to Botox injection that requires only flexible nasopharyngeal endoscopy and careful evaluation of the anatomic landmarks. This technique has been used successfully on 13 patients, and objective pretreatment and posttreatment measures are reported. PMID- 1444095 TI - Quantitative mapping of the effect of botulinum toxin injections in the thyroarytenoid muscle. AB - Spasmodic dysphonia has been successfully treated by thyroarytenoid muscle injections of botulinum toxin (Botox) with dosages ranging from 0.625 to 25 U. In some patients, excessive paralysis with resulting breathiness and aspiration have been noted. In order to maximize the efficiency of Botox injections, the histologic effects of various Botox dosages were examined in the dog. Nine canine thyroarytenoid muscles were injected with 0.5 to 12.5 U of Botox. After 24 hours, the recurrent laryngeal nerve to the injected muscle was electrically stimulated in order to deplete the glycogen within the muscle fibers. Frozen sections of this muscle were then stained for glycogen. Those fibers that retained their glycogen were presumed paralyzed by the Botox injection. The extent of paralysis was found to be dose-related from 1.0 to 7.5 U. At 10 U and above the muscle was completely paralyzed. Spread of the toxin to the lateral cricoarytenoid muscle was seen at doses as low as 1.0 U. Clearly, doses less than 10 U appear sufficient for clinical paralysis. PMID- 1444096 TI - Continuous positive airway pressure as a promoter of laryngospasm during halothane anesthesia. AB - Twenty mongrel dogs were anesthetized with halothane 2.0%, 1.25%, 0.94%, and 0.63% in oxygen. Thyroarytenoid (TA) and posterior cricoarytenoid (PCA) electromyography (EMG) tracings were recorded with the animal at rest, following mechanical irritation of the glottis, and during 20 mm Hg continuous positive airway pressure (CPAP) following either airway occlusion or hyperventilation. Adductor laryngospasm was defined as continuous tonic TA EMG activity, silent PCA EMG, and vocal cord adduction. Abductor laryngospasm was defined as continuous tonic PCA EMG activity, silent TA EMG, and vocal cord abduction. Combined laryngospasm was defined as continuous tonic PCA and TA EMG activity, with variable vocal cord position. The incidence of adductor laryngospasm following mechanical irritation was 30% to 50%. The combined incidence of laryngospasm during application of CPAP following airway occlusion or hyperventilation was 25% to 50%, and differed from the incidence of irritation-induced adductor laryngospasm by 5% or less at the same anesthetic level. Continuous positive airway pressure appears to be a stimulant of laryngeal muscle spasm comparable to mechanical irritation of the glottis. PMID- 1444097 TI - Laryngotracheal reconstruction in adults with the sternocleidomastoid myoperiosteal flap. AB - Subglottic or tracheal reconstruction may be required in cases of subglottic stenosis, invasive thyroid carcinoma, or trauma. The sternocleidomastoid myoperiosteal flap uses clavicular periosteum on a muscle pedicle to provide vascularity. Clavicular periosteum is fibrous and durable and will conform to the shape of the trachea, forming bone to provide stability to the airway. The procedure is relatively simple and involves single-stage reconstruction. Success has been achieved in reconstruction of long-standing subglottic and/or tracheal stenosis and in cases of extreme tracheal defects. On the basis of 8 years' experience with this flap, we present the results from a series of 26 patients who underwent subglottic or tracheal reconstruction with the sternocleidomastoid myoperiosteal flap. Twenty-five of the 26 patients were successfully decannulated. Complications have been expanded to include one case of osteomyelitis of the sternum with mediastinitis, and 1 patient required revision. Subsequently, modifications of technique and patient management have been adopted. The complications compare favorably in frequency and in seriousness with those of other techniques for laryngotracheal reconstruction. We describe additional experience with this procedure and longer follow-up to establish its position as a first-line reconstructive approach for widespread clinical use. PMID- 1444098 TI - Detection of regulatory factors of lymphokine-activated killer cell activity in head and neck cancer patients treated with interleukin-2 and interferon alpha. AB - Interleukin-2 (IL-2) and interferon-alpha (INF-alpha) are biologic modifiers that have met with limited clinical success in the treatment of human malignancies. We conducted a phase 2 trial of IL-2-IFN-alpha in patients with advanced or unresectable squamous cell carcinoma of the upper aerodigestive tract. Two patients were analyzed sequentially for serum induction phase-blocking factors of lymphokine-activated killer (LAK) cell activity in their therapy. Serum also modulated LAK activity independent of autologous or allogeneic effector cells. Significantly inhibitory serum samples were stable in multiple freezings and thawings. Heat-treating the inhibitory serum, at 56 degrees C for 30 minutes, only partially removed the serum inhibitory capacity. Sequential analysis of p55 and p75, subunits of IL-2 receptors, showed that absence of effector cell lytic activity was associated with markedly decreased fluorescence of the IL-2Rp75 subunit only. No significant alteration of the IL-2Rp55 subunit occurred with therapy. These studies support the theory that lymphocyte and multiple serum factors, developing during IL-2-IFN-alpha therapy, regulate the induction of in vitro LAK activity. Further understanding of these factors may lead to improvements in biologic modifier therapy. PMID- 1444099 TI - Bilateral choanal atresia associated with malformation of the anterior skull base: embryogenesis and clinical implications. AB - A number of craniofacial and systemic malformations have been described in association with choanal atresia. We report a case of bilateral choanal atresia associated with congenital absence of the cribriform plate, crista galli, and perpendicular plate of the ethmoid bone. The anterior skull base defect was detected by using high-resolution computed tomography with three-dimensional reconstructions. The findings support the mesodermal flow theory of choanal atresia, in which there is excess migration of neural crest cells into the developing nasal septum and posterior choanae. This occurs at the expense of cells that would otherwise form the rest of the ethmoid complex. Clinical implications include the need for adequate preoperative imaging of the anterior skull base and consideration of potential intracranial complications during surgical repair. PMID- 1444100 TI - Laryngeal adenocarcinoma, not otherwise specified, treated with carbon dioxide laser excision and postoperative radiotherapy. AB - Glandular carcinomas of the larynx are aggressive neoplasms that comprise less than 1% of all laryngeal malignancies. Adenocarcinoma, not otherwise specified, is the most common histologic type. The rarity of these lesions has prohibited clarification of definitive therapy. Traditionally, radical surgery is performed because of the usually high stage at presentation and the relative insensitivity to radiotherapy. A case of glottic T1 adenocarcinoma, not otherwise specified, is reported. The tumor presented clinically as a vocal fold granuloma. The treatment modalities included endoscopic excision with the carbon dioxide laser and postoperative radiotherapy. The patient has been followed up for 39 months without evidence of recurrence or metastases. The current literature is reviewed in regard to treatment of laryngeal glandular carcinomas. PMID- 1444101 TI - Facial canal dehiscence: histologic study and computer reconstruction. AB - The incidence, location, shape, and dimensions of dehiscences in the facial canal to the middle ear space were studied in 160 temporal bones obtained from 129 individuals 24 gestational weeks to 109 years of age at death by means of light microscopy and our computer reconstruction and measurement method. Dehiscences were observed in 95 of the 129 individuals (74%) and in 119 of the 160 bones (74%). The incidence was found to be quite high among fetuses and newborns, lowest in individuals in their twenties and then again quite high in the geriatric population (chi 2 test, chi 2 = 5.45 and 4.41, p < .05). The most frequent site of dehiscence was the oval window area, particularly in its posterior half (57% of all ears) on the inferior to inferomedial aspects of the canal; these dehiscences were clearly demonstrated in reconstructed images. The incidence of dehiscence in the area of the cochleariform process was 16%, and all these dehiscences were on the lateral to superolateral aspect of the canal. The second genu area and the mastoid portion were sites of dehiscence in 21% and 18%, respectively, of specimens; more than half of the dehiscences in the second genu area and mastoid portion were on the lateral to anterolateral and posterior aspects of the facial canal, respectively. The shape of the dehiscence tended to be oval in the oval window area, but rather irregular in the other areas. The dehiscences ranged from 0.4 to 2.64 mm in length, from 0.12 to 1.59 mm in width, and from 0.03 to 1.87 mm2 in surface area. The proximity of these dehiscences to the field of otologic surgery is stressed. PMID- 1444102 TI - Skull base dumbbell tumor: surgical experience with two adolescents. AB - Pediatric skull base tumors are rare and until recently were considered unresectable. We present two patients with tumors of similar anatomic position with an extracranial component in the infratemporal fossa and parapharyngeal space, an isthmus at the foramen ovale, and a superior component in the middle cranial fossa in the region of the cavernous sinus. A 15-year-old girl experienced contiguous spread of a spindle cell sarcoma; an 18-year-old boy developed a chondrosarcoma. A middle fossa approach provided the advantage of surgical avoidance of structures such as the middle ear and mastoid, facial nerve, and mandible. Postoperative recovery was rapid. Our impression is that preoperative carotid artery occlusion and a middle fossa approach for tumor resection can be performed in a young patient with acceptable morbidity and at least short-term benefit. Surgery can, therefore, provide an additional therapeutic approach to complement irradiation and chemotherapy. PMID- 1444103 TI - Rat model for a vascularized laryngeal allograft. AB - A new rat model was developed to reexamine the potential for laryngeal transplantation. The final anatomic derivation evolved from two earlier developmental phases. The first model had only a single arterial anastomosis; the second had an end-to-end arterial anastomosis with an end-to-end arteriovenous shunt. The final product employed an end-to-side arterial shunt and an end-to side arteriovenous shunt for revascularization. The allografts were sited in tandem with the intact recipient larynges and were not innervated. A total of 16 animals were studied in phase 3; 2 died and the remaining 14 had a 64% arterial patency at intervals of 1 to 14 days. Our purpose is to detail the relevant technical considerations of this new model and compare it with historical controls. PMID- 1444104 TI - Magnetic resonance angiography of synchronous bilateral carotid body paragangliomas and bilateral vagal paragangliomas. PMID- 1444105 TI - Embryoma (sialoblastoma) of salivary glands. AB - There are four clinicopathologic categories of the exclusively major salivary gland tumors that present in the perinatal period. The two with the smallest representation among the 20 cases reported to date are those with a hamartomalike appearance and those with benign adult equivalents--the pleomorphic and monomorphic adenomas. Five cases have been undifferentiated or basaloid salivary carcinomas. Embryomas (sialoblastomas) are the most numerous. These tumors manifest a histologic phenotype like that of the epithelial anlage of the salivary glands, albeit in an arrested state of differentiation. PMID- 1444106 TI - [Primary cutaneous lymphoma, with the exception of mycosis fungoides]. AB - Cutaneous lymphomas other than mycosis fungoides (MF) form a rare and heterogeneous group. Their clinical behavior remains largely unknown. In this study, the clinical, immunohistological characteristics and follow-up data of 27 well-documented cases of primary cutaneous lymphomas other than MF, limited to the skin (stage IE) were reviewed. The tumors were divided into large-cell lymphomas (LCL) (21/27 = 77 p. 100) and small-cell lymphomas (SML) (6/27 = 23 p. 100). A B-cell phenotype was most often expressed by cutaneous lymphomas (23/27 = 85 p. 100). The clinical course of cutaneous lymphoma was closely dependent upon the histological subtype. Fourteen patients with LCL were treated by radiotherapy alone. Nine patients (64 p. 100) relapsed within two years post-treatment. Seven of them relapsed in the skin outside the initial site, suggesting that radiotherapy alone is not an adequate treatment for these patients. The preliminary results concerning 7 other patients with LCL treated with an initial third generation polychemotherapy regimen are presented. PMID- 1444107 TI - [Atypical cutaneous mycobacterium diseases. Results of a national survey]. AB - We report the results of a retrospective inquiry concerning atypical cutaneous mycobacterioses in France over the last 5 years. Ninety-two cases were observed, contracted from aquariums (50 p. 100), in swimming pools (4.4 p. 100) and as a result of mesotherapy (15.2 p. 100); 66.3 p. 100 of the patients had no other pathology; 17.4 p. 100 were immunodepressed. Bacteriological examination was positive in 44.7 p. 100 of the cases; swabbing, scratching and punturing were better than biopsy to obtain a bacteriological culture. Mycobacteria were identified in 59.8 p. 100 of the cultures. In order of frequency, the pathogens were Mycobacterium marinum (from aquariums), M. chelonae (from iatrogenic lesions) and M. avium-intracellulare (in immunodepression). M. fortuitum, M. ulcerans, M. flavescens, M. haemophilum and M. kansasii were rare. The formation of epithelial giant-cell granulomas was observed in patients without any other pathology. Non-specific infiltration was found in patients with immunodepression and bacteriological examination was often positive in those with non-specific infiltrates. The treatment of atypical cutaneous mycobacterioses is always difficult; third generation tetracyclines and antibacterial combinations are often prescribed, but the results of in vitro tests are not reproducible in vivo. New antibiotics, such as clarithromycin, quinolones, ansamycin and clofazimine, are currently being tested. PMID- 1444108 TI - [Cutaneous reactions to cold of buttocks and thighs]. PMID- 1444109 TI - [Basex paraneoplastic acrokeratosis associated with acquired ichthyosis, pigmentation disorders and pruritus: a late disclosure of laryngeal neoplasms]. PMID- 1444110 TI - [Polyvalent intravenous immunoglobulins: their use in dermatology]. PMID- 1444112 TI - [Apropos of systemic scleroderma and pregnancy]. PMID- 1444111 TI - [How to treat molluscum contagiosum of eyelids when curettage and liquid nitrogen may be hazardous?]. PMID- 1444113 TI - [A case for diagnosis: scleroatrophic lichen of the glans]. PMID- 1444114 TI - [Varicella and pregnancy]. PMID- 1444115 TI - [Risks of topical treatments in pregnancy]. PMID- 1444116 TI - [Facial granuloma]. PMID- 1444117 TI - [Treatment of discoid lupus erythematosus]. PMID- 1444118 TI - [Treatment of molluscum contagiosum (except in AIDS)]. PMID- 1444119 TI - [The green and the red in pharmacy]. AB - The green colour is historically used as a symbolic mark for the French Pharmacy. Green and red are important for the labelling of dangerous and toxic drugs respectively. Etymological channels about green and red are studied for many words belonging to the pharmaceutical vocabulary and the authorized dying matters. Discussion is led in the field of the semantic signification in Pharmacy at several times. PMID- 1444120 TI - [Immunocompetence in the elderly]. AB - Ageing is associated with a progressive decline of the immune systems, characterized by impaired T cells and changes in the antigenic repertory related to both the humoral and cell-mediated immune responses. The major alterations have been demonstrated in the T cells which undergo functional changes, such as a decrease in precursor frequencies of helper and cytotoxic T-cells, and accumulation of T cells which does not respond to activators. In general, T cell dependent, cell-mediated responses decline with age. The elderly are at great risk for low consumption of proteins and of several micronutrients, such as zinc or vitamins C, E and B6 which play a critical role in the maintenance of normal immune function. As a consequence, the incidence of inflammatory and infectious disease, auto-immune disorders, cutaneous pathological changes, and skin cancers increases. Morbidity and mortality rates due to tetanus, pulmonary infections and influenza remain high in elderly populations. Depressing the rate of immunosenescence and restoring a normal immunocompetence in the elderly may involve improved nutrition through proteins, micronutrients and vitamins, and should deal with the economic and psychosocial problems of the elderly. Vaccinations against tetanus, pneumococcus and influenza proved to be efficacious and well-tolerated. Consequently, they should be applied systematically to non protected elderly individuals. PMID- 1444121 TI - [Towards a status of pharmacists responsible to humanitarian associations?]. AB - The creation and aims of ANPCM (Association Nationale Pharmaceutique pour la Collecte des Medicaments = National Chemists for Drug Collection) are recalled. In 1988, only a simple letter of the French Ministry of Health gave recommendations concerning left unemployed drugs. A clear codification of the status of the Responsible Chemist of Humanitarian Associations Collecting Drugs should therefore be useful. PMID- 1444122 TI - [Comparative study of absorbent dressings]. AB - The quality of six absorbent dressings of fluffy padding has been compared. The study show one variability of the quality of products which can influence on scarred up the wounds. The part of hospital pharmacist in the choice of this articles is very important. PMID- 1444123 TI - [5-Fluoro (3H) pyrimidine-4-ones: synthesis, reactivity and pharmacological properties]. AB - Fourteen fluoro pyrimidine-4-ones, four fluoro bispyrimidine-4-ones and two fluoro pyrimidine-4-ones with fused ring have been prepared. The reactivity of the carbonyl group of two pyrimidine-4-ones phosphorus oxychloride was studied. The 4-chloro pyrimidines reacted with ammonia or morpholine giving 4-substituted pyrimidines. Eight compounds are evaluated for their anti-inflammatory and anti convulsivant properties: they were found to be weakly active against oedema and three of them protected rats form tonic convulsions. PMID- 1444124 TI - Facial video image processing: standard facial image capturing, software modification, development of a surgical plan, and comparison of presurgical and postsurgical results. AB - Video imaging is a maturing technology that will challenge the 35-mm photograph in its usefulness to the plastic surgeon. Computer modification of a patient image communicates to the patient a reconstructive plan. A comparison of the presurgical and postsurgical images keenly sensitizes the surgeon to the results of surgical technique. The equipment required for video imaging also provides a powerful tool for creation of presentation graphic prints (for publication), 35 mm slides, and, with additional software, educational video tapes. I describe here a video method for standard alignment of patients. The preoperative and modified patient image (surgical plan) is compared with the postoperative image to determine the degree of success in achieving the reconstructive goals. Comparison of standardized presurgical and postsurgical images offers the surgeon greater objectivity in his analysis of the surgical technique than is possible by comparison of clinical photographs. The value of video imaging to the reconstructive surgeon magnifies the success (or disappointment) of surgical technique. PMID- 1444125 TI - Soft-tissue reconstruction of the face: a comparison of dermal-fat grafting and vascularized tissue transfer. AB - Eight patients treated with dermal-fat grafts and 8 patients treated with vascularized tissue transfer were retrospectively reviewed to determine the efficacy of the two methods in the treatment of the soft-tissue defects in Romberg's disease, clefting syndromes including hemifacial microsomia, and traumatic defects. Follow-up averaged 4 years and ranged from 1 to 9 years for the vascularized transfers and 1.5 to 11 years for the dermal-fat grafts. Both techniques were able to provide enduring augmentation. The vascularized transfers were able to provide a greater amount of augmentation. We conclude that dermal fat grafting is a satisfactory technique for mild to moderate defects, but that vascularized transfers are required for moderate to severe defects. PMID- 1444126 TI - Bipedicled fasciocutaneous flaps in the lower extremity. AB - It is well known that a bipedicled skin flap permits survival of longer flaps due to the secondary recruitment of vascularity. Inclusion of the deep fascia with such a flap, obeying the principles of the single-pedicled fasciocutaneous flap, provides even greater security for the immediate transposition of yet larger or riskier flaps without the need for delay maneuvers. This variation is especially valuable for the management of difficult wounds encountered in the lower extremity when no other local options may be available. Thirteen local bipedicled fasciocutaneous flaps including both vertical and horizontal orientations, without isolation of any discrete fascial perforators, have been successfully used for soft tissue coverage in the distal leg and ankle with only three (23%) minor complications as untoward sequelae. Another major advantage of this bipedicled version of the fasciocutaneous flap was that the inclusion of a distal pedicle simultaneously may be designed to prevent bone or tendon exposure at the donor site that otherwise frequently is a concern with a unipedicled flap. PMID- 1444127 TI - The chondromucosal sleeve for the secondary correction of the unilateral cleft lip nasal deformity. AB - We present a new procedure for the secondary correction of the cleft lower lateral cartilage in the unilateral cleft lip nose deformity. A chondromucosal sleeve based entirely on mucosa is combined with an open rhinoplasty to facilitate a medial to lateral rotation of the cleft lower lateral cartilage. In 52 patients, we have found that this technique improved the results of the deformity and is more successful than lateral to medial rotation procedures alone. The chondromucosal sleeve adds to the medial to lateral rotation techniques the ability to obtain a controllable and reproducible result. PMID- 1444128 TI - Distally based turnover flap and preputium plasty for distal hypospadias repair: a preliminary report. AB - A surgical procedure for hypospadias correction using a proximally based turnover flap, glanuloplasty, and preputium plasty is described. The flap is vertically disposed and distally based on the external urethral meatus, and the shape is spatulated. It is dissected from proximal to distal, turned over, and sutured to the glans to reconstruct the missing portion of urethra. A glanuloplasty is performed and the preputium is restored by careful reconstruction of its inner and outer surface. The technique is useful in distal penile and glanular hypospadias without chordee or meatal stenosis. Very good functional and aesthetic results, and no complications, were obtained with this technique. Preliminary results and a 3-year follow-up are presented and discussed in this report. PMID- 1444129 TI - A venous thrombosis technique for experimental thrombolytic therapy. AB - A technique for the experimental creation of a venous thrombus in the rat is described. This technique involves a circumferential stretching of the intima, which maximizes intraluminal collagen exposure without complete separation of the vessel wall. This thrombotic method was 94.4% effective at complete vessel occlusion after 24 hours in 40 treated veins. This model is of particular interest in the in vivo evaluation of thrombolytic agents in the laboratory setting and as an adjunct to thrombotic complications in microsurgery. PMID- 1444130 TI - Cutaneous vascular anatomy of the thoracic region of the dorsum and its role in flap design in the rat. AB - The cutaneous vascular anatomy of the proximal one-half of the dorsum (the thoracic region) and its role in flap design was studied in the rat. The investigation included anatomical dissection, ink injection into the axial artery, and flap harvesting in live animals. Anatomical dissection and india ink injection of the thoracic region revealed that the skin derives its principal blood supply from the lateral thoracic artery. The cutaneous vascular territory of the lateral thoracic artery was defined as follows: the medial border, along the midline of the back from the level of the inferior angle of the scapula to the lower border of the last rib; the lateral border, anterior axillary line corresponding with the length of the medial border; the cephalic border, a line joining the medial and lateral border at the level of the inferior angle of the scapula; and the caudal border, a line corresponding to the lower border of the last rib. Bilateral vascular pedicle island cutaneous flaps were harvested in living rats based on the vascular territory demarcated by India ink injection. All flaps survived; hence, this flap is reliable, with consistent vascularity, and is easy to harvest, and therefore, can be used as a vascular pedicle experimental model to study flap hemodynamics. PMID- 1444131 TI - Squamous cell carcinoma following breast augmentation. AB - Controversy over the safety of breast implants has increased significantly over the past several years. Several companies have discontinued their manufacture of silicone implants. Although there have been reports of breast cancer developing in a patient who previously had undergone breast augmentation, a review of the literature has failed to reveal a patient with cancer arising from the breast implant capsule. We present a woman with squamous cell carcinoma apparently arising from an implant capsule 15 years after breast augmentation. PMID- 1444132 TI - Tissue expansion of sensate skin for pressure sores. AB - The surgical treatment of pressure sores has improved with the development of many techniques to provide coverage of these defects. Few deliver sensate coverage. This report describes tissue expansion of back skin to provide definitive sensate coverage of a pressure sore, thereby preventing its recurrence. Follow-up of 5.5 years is presented with a review of the literature. PMID- 1444133 TI - Restoration of the mandible by full-thickness calvarial bone flap. AB - Two patients with reconstruction of a massive mandibular defect with vascularized full-thickness calvarial bone flaps are reported. In Patient 1, the mandibular body developed osteomyelitis and once was replaced with a metallic prosthesis. The prosthesis later perforated the skin and was removed. Full-thickness calvarial bone flaps were elevated bilaterally to reconstruct the mandibular body. In Patient 2, the mandible was totally destroyed by invasion of squamous cell carcinoma. The lower one-half of the face was resected and replaced with a large island scalp flap with full-thickness calvarial bone. PMID- 1444134 TI - Misdiagnoses: a timely reminder. AB - This case report of an occult infection masquerading as palindromic arthritis was misdiagnosed for almost 2 years. The episodic bouts of erysipelas were not obvious, and it was even suggested that the silicone implanted 7 years previously could possibly be inciting an autoimmune disease. Approximately 2 years after the onset of the recurrent episodes of fever, myalgias, and arthralgias, coagulase negative staphylococci were found residing in the valve stems of bilumen breast implants, which were removed. The symptom complex disappeared and has not recurred. PMID- 1444135 TI - Benign mesodermal tumors producing nasal deformity. AB - Tumors of neurogenic (ectodermal) origin are well-described causes of nasal deformity. We present a patient with a benign mesodermal tumor (unclassified spindle cell) producing nasal deformity. A retrospective review of the two senior authors' records provided an additional three patients with nonvascular benign mesodermal nasal masses (fibroma and leiomyoma). Benign mesodermal masses can occur in the midline of the nose and need to be differentiated from dermoids and gliomas. Misdiagnosis is the rule. Excisional biopsy is required for definitive diagnosis. In addition, excisional biopsy is curative and can help to minimize the subsequent nasal deformity if performed early in the disease process. Immunohistochemical and electron microscopy may be required for comprehensive diagnosis and treatment. PMID- 1444136 TI - Reconstruction of facial contour deformity with the buccal fat pad flap. AB - The primary goal in unilateral facial reconstruction is to mirror, with three dimensional or volume symmetry considerations, the contralateral normal structures in form and function. This case study indicates that, along with other proved options, the buccal fat pad can successfully be used to add small to moderate volume in facial reconstructions. PMID- 1444137 TI - Abdominoplasty following colostomy. AB - An abdominoplasty was performed on a 57-year-old woman, 5 years after she had undergone a permanent colostomy for ulcerative colitis. The abdominoplasty was performed in an attempt to reduce the increased abdominal girth thought to be responsible for excess leakage of effluent from the colostomy site with changes in posture and increased abdominal pressure. A simple abdominoplasty flap was designed to decrease the excess abdominal tissue without impinging on the colostomy site. The result was dramatic in accomplishing the set-out goals. An added bonus was a reversal of preoperative urinary incontinence. This outcome is thought to be a result of more efficient voiding after abdominal muscle plication and stabilization. PMID- 1444138 TI - Prediction of nipple viability following reduction mammoplasty using laser Doppler flowmetry. AB - The assessment of viability of a pedicled nipple-areola complex after reduction mammoplasty frequently may be frustrating due to equivocal clinical signs of adequate blood flow. Although conversion to a composite graft is always a safe option, the aesthetic result may be inferior. An objective monitor might be beneficial to maximize the surgical outcome while minimizing the risk of nipple necrosis. Laser Doppler flowmetry provides a safe, simple, and noninvasive objective monitor that allows continuous intra-operative or postoperative evaluation of nipple perfusion. An evaluation of 31 nipples in 16 patients undergoing breast reduction based solely on the surgeon's judgment would have resulted in 9 false positive or negative results as compared with 3 using the laser Doppler. Four nipples that may otherwise have been converted to free grafts were instead preserved. However, conclusions from this data limit the laser Doppler as a valuable supplement, but not a replacement, for experienced clinical acumen. PMID- 1444139 TI - The use of bifid nasolabial flaps in the reconstruction of the nose and columella. AB - The repair of defects involving the tip of the nose and columella still pose a problem in reconstructive surgery. The use of bifid nasolabial flaps versus other reconstructive methods is discussed in this article. PMID- 1444140 TI - Lower facial recontouring in craniofacial asymmetry. AB - The secondary correction of facial asymmetry due to early posterior cranial deformation is presented. The combination of mandibular skeletal reduction of the gonial angle and inferior border, masseter muscle thinning, and auricular setback can be an effective camouflage technique when the facial skeleton and occlusion do not require repositioning. PMID- 1444141 TI - Nasal tampon packing in rhinoplasty: a simple and safe method of hemostasis. AB - To absorb bleeding and pack the nasal cavities after rhinoplasty, a sterile commercial vaginal tampon was used. It has the following advantages: high absorbency, round configuration, and safety removal cord included to preclude gliding into the nasopharynx. PMID- 1444142 TI - Vector-running subcuticular sutures in high-tension and high-mobility areas. AB - Routine cuticular sutures pierce the epidermis, and if left in place long enough, will noticeably scarify, a process called "tracking." Alternatively, the running subcuticular suture has the advantage of minimizing suture tracking, especially following a prolonged usage, because it does not pierce the epidermis along most of its course. A "hybrid" modification of these two sutures, described herein, allows for prolonged tight closure under high tension in high-movement areas, avoidance of tracking, and rapidity of placement. This innovation is called the vector-running subcuticular suture. PMID- 1444143 TI - Of elephants and periprosthetic cancers. PMID- 1444144 TI - Re: Structure and construction: the system of skin flaps. PMID- 1444145 TI - Re: The polyurethane foam covering the Meme Breast Prosthesis: a biomedical breakthrough or a biomaterial tar baby? PMID- 1444146 TI - [HIV infection. Natural history, classification, treatment and occupational risk]. PMID- 1444147 TI - [Ambulatory surgery. Apropos of an experience in hand surgery]. PMID- 1444148 TI - [Peroperative cholangiography in cholelithiasis. Results of a multivariate analysis]. AB - This study was done to select patients with a low risk of common bile duct (CBD) stones in whom operative cholangiography could be avoided. Operative cholangiography was performed upon 511 patients. Two different groups of patients were identified: patients with CBD stones visualized by CBD exploration (n = 90) and patients with no CBD stones at the time of operative cholangiography (n = 42). Multivariate analysis (stepwise logistic regression) showed that five variables were correlated with the presence of CBD stones: size of CBD equal to or greater than 12 millimeters, gallstones equal to or less than 10 millimeters, advanced age, chronic or acute cholecystitis and pas history of biliary colic. Using a scoring system, a group of patients with a low risk (less than 2%) of CBD stones could be easily determined. In this group of patients, operative cholangiography may be avoided. PMID- 1444149 TI - [Hartmann's procedure. A retrospective study of 86 cases]. AB - The purpose of this retrospective study is to define current indications and results of Hartmann's procedure (H). From 1978 to 1989, 86 H were performed, 52 (60%) as emergency surgery. Indications were: colo-rectal cancer (37): 15 complicated and 22 as an elective procedure, diverticular disease acute or complicated (24), ischemic colitis (10), volvulus of the pelvic colon (5), inflammatory bowel disease (4), colonic perforation (3), traumatic hematoma of the sigmoid mesocolon (1). Fourteen patients died after operation (mean age: 79). There was no death after elective H for cancer. Post-operative complications were numerous: pulmonary (25%), abdominal would sepsis or disruption (21%), rectal strump leakage (14%), the later being harmless due to the associated Mickulicz drainage. Seven patients were reoperated on for necrosis of the colonic stoma. Mean initial hospital stay was 31 days. Restoration of the gastrointestinal continuity was done in 27 cases (37% of the surviving patients, 76% of the diverticular diseases). The authors conclude that for complicated diverticular disease H procedure improves survival without preferable continuity. For cancer, H procedure is permanently compromising gastrointestinal in the elderly to hazardous low anastomosis, and to palliative abdomino-perineal resection. PMID- 1444150 TI - [Supramalleolar derotation osteotomy for torsion of the leg in children and adolescents. Techniques and results: apropos of 22 patients (32 legs)]. AB - We have performed 32 supramalleolar osteotomies described by Mc Nicol to correct excessive internal or external tibial torsion in 22 patients (aged from 4 to 8 years, with different indications, with a follow-up of 16 months to 7 years). The consolidation of the osteotomy was obtained in 6 weeks. Eighteen patients (27 osteotomy) have a good result, 2 results are fair and 2 patients have a poor result. The indications for correction of excessive internal or external tibial torsion are very uncommon, and reserved to cases with functional disorbility of fitting appliances, or unaesthetic or uncomfortable gait. PMID- 1444151 TI - [Echo-endoscopy of the digestive system]. AB - Endoscopic ultrasonography of the gastrointestinal tract allows a precise ultrasound study of the accessible gastrointestinal walls (oesophagus, stomach, duodenum, rectum) and, through these walls, of the adjacent organs (lymph nodes, posterior mediastinum, pancreas, extrahepatic biliary ducts and perirectal region). This method is better than computerized tomography to evaluate the local and regional extension of oesophageal and cardial carcinomas producing little or no stenosis and of gastric and rectum carcinomas and lymphomas. It is the examination of choice to detect a perianastomotic recurrence of these cancers and to evaluate submucosal tumors of the gastrointestinal tract. This method, with no morbidity, is better than computerized tomography or ultrasonography in the aetiological diagnosis of obstacles in the biliary tract and in the diagnosis and pretherapeutic assessment of pancreatic cancer or endocrine tumors. PMID- 1444152 TI - [Intraperitoneal resorbable mesh in the prevention of postoperative wound dehiscence. A comparative study]. AB - The purpose of this study was to compare efficiency of polyamide mesh externally applied to the skin and intraperitoneal resorbable mesh of polyglactine 910, for the prevention of wound dehiscence. Two consecutive and homogenous groups of 100 patients, operated by the same surgical team and presenting one or more risk factors of evisceration, were retrospectively compared. Use of intraperitoneal polyglactine mesh, significantly reduced rate of wound dehiscence (4% vs 13%), lowered frequency of reoperation in eviscerated patients (25% vs 61%), but did not improve prognosis of this complication (50% mortality). Potential effect of resorbable mesh on late fascial disruption remains controversial. PMID- 1444153 TI - [Darier-Ferrand dermatofibroma. An unusual tumor of the soft tissues]. AB - Darier and Ferrand dermatofibroma is a rare skin tumour arising in the dermal connective tissue. It has a slow course over several years and presents very unusual histological features. It is characterised by a marked potential for local recurrence, frequently multiple due to insufficient primary resection. It has a very low metastatic potential. Its diagnosis is difficult but essential in order to perform an appropriate surgical procedure which ensures its excellent prognosis. PMID- 1444154 TI - [Peristomal pyoderma gangrenosum after colectomy for Crohn disease. Successful medical treatment]. AB - A case of Pyoderma gangrenosum with two different abdominal sites in a female patient suffering from colonic Crohn's disease is presented. Local trauma on the midline scar of an incisional hernia and around the stoma were the possible triggering factors. Despite the major abdominal wall defect and an infected parietal collection, steroid therapy was very effective without the need for surgery. PMID- 1444155 TI - [Endometriosis and diaphragmatic defect in catamenial pneumothorax]. AB - Two cases of catamenial pneumothorax are reported, a rare condition characterized by its sudden occurrence in a female patient between the ages of 30 and 40 years, always at the onset of the menstrual cycle. Its exact origin is unknown, but the frequent co-existence of endometriosis and a defect in the diaphragm suggests that endometriosis may be important in the etiology both of the pneumothorax and the diaphragmatic lesion. Pelvic endometriosis was present in both our patients, one of whom also had diaphragmatic endometriosis. The treatment of the pneumothorax in both our cases consisted of pleural decortication with excellent results so far. PMID- 1444156 TI - [Evaluation of the arrhythmogenic potential 3 months after myocardial infarction]. AB - An evaluation of the ventricular arrhythmia potential was conducted 3 months after a myocardial infarction (anterior n = 32, inferior n = 58) in 90 patients with a group mean age of 58 +/- 9.3 years, using 24-hour ambulatory ECG monitoring, an exercise test, recording of late ventricular potentials and programmed right ventricular stimulation. Eighteen patients (20%) had a ventricular extrasystole > or = Lown grade III on the Holter, which was more frequent in patients with ventricular dyskinesia (41% vs 15%; p < 0.05); 10 patients (11.1%) had ventricular extrasystoles > or = Lown grade III during the exercise test; 19 patients had late ventricular potentials. Programmed ventricular stimulation induced monomorphic ventricular tachycardia in 10 patients (11.1%) (sustained, n = 5, unsustained n = 5) and the prevalence of late ventricular potentials was higher in this group (60% vs 16.2%; p < 0.01). In the medium term (32 months), 2 patients had died: one suddenly and the other of a recurrence of myocardial infarction. Five patients had an episode of spontaneous ventricular tachycardia. The risk of sudden death or ventricular tachycardia was higher in patients with late ventricular potentials (positive predictive value = 21%) and in patients with electro-induced ventricular tachycardia (positive predictive value = 66%). In the absence of late ventricular potentials, the risk of a serious arrhythmic event is slight (2.8%). After myocardial infarction, the presence of late ventricular potentials can be used to isolate a group of patients with a high risk of serious ventricular arrhythmia; this risk is higher if programmed ventricular stimulation triggers monomorphic ventricular tachycardia. PMID- 1444157 TI - [Nocturnal-diurnal changes of norepinephrine blood levels in patients with chronic cardiac insufficiency. Practical values]. AB - The purpose of this study was to investigate circadian changes in noradrenaline (norepinephrine) levels in patients presenting with congestive heart failure. Eighteen patients were investigated with a group mean age of 66 years, 12 in NYHA class III and 6 in class IV. The cause of the heart failure was ischemia in 7 cases, valvular in 1 case and idiopathic in the other 10 cases. The mean follow up time of the disease was 3.9 years. Six healthy volunteers were investigated following the same protocol. Blood samples were taken while the patient was lying down over a period of 24 hours, after installing a peripheral venous catheter. The assay was carried out by means of high performance liquid chromatography with electrochemical detection. In the controls, the mean noradrenaline level (norepinephrine) was 220 +/- 62 pg/ml, with daytime peaks. The heart failure patients showed a high mean level (230 +/- 404 pg/ml), with less daytime variability than the controls (92% vs 127%; p < 0.05). The 8 a.m. value was reproducible, and there was close correlation between this value and the mean value for the 24 hours (p < 0.001). Thus, the morning sample provides a good estimation of the levels over the 24 hours. PMID- 1444158 TI - [Predictive factors of regularization and maintenance of sinus rhythm in chronic atrial fibrillation]. AB - The aim in treating chronic atrial fibrillation, is not limited to simply achieving immediate regularization. What matters, is sustaining the sinus rhythm. The various methods of regularization, using either medical procedures or cardioversion, involve constraints and risks. Investigation of the relapse predicting factor is of great value in evaluating the benefit/risk ratio. For regularization, the absence ultrasound signs of heart disease, an undilated left atrium, recent atrial fibrillation and all forms of heart disease which are curable, albeit surgically, are indicative of success. With regard to prophylaxis, relapses occur more frequently in cases involving mitral valve disease, long-standing atrial fibrillation or a dilated left atrium. PMID- 1444159 TI - [Extracorporeal circulation in acute ischemia of the lower limb with late detection]. AB - The authors report a case of acute limb ischemia in a 19 years old patient seen at 9 hours of the injury. They describe a technique of "washing-reperfusion" by a cardio-pulmonary limb bypass (CPLB). Blood pH and kaliema measurements during CPLB were noted. The good clinical result except on the initial nerves deficit, should lead to think that this technique could take a place in the treatment of acute limb ischemia seen lately. PMID- 1444160 TI - [Apropos of a rare cause of torsades de pointe: hypokalemia caused by dietary deficiency]. AB - The authors report a case of wave burst arrhythmia in a young immigrant woman of Laotian origin aged 32. The main cause of the arrhythmia was related to potassium deficiency of dietary origin. Some contributory factors may have had a promoting effect: theophylline treatment, beta-mimetics and adrenaline (epinephrine). This case can therefore be related to the cases of wave burst arrhythmia and hypokalemia previously reported in anorexic subjects. This case suggests that special attention should be paid to the diet of some ethnic groups who have been displaced by economic causes. Their very unusual dietary habits may induce or aggravate hypokalemia, which may also be promoted in some cases by drugs. Some treatments should therefore be introduced with caution in this context due to the potential risk of inducing severe arrhythmia. PMID- 1444161 TI - [Efficacy of the combination of nicardipine-enalapril and atenolol in severe hypertension secondary to chronic renal disease]. AB - The antihypertensive efficacy of combination therapy with N-E-A was evaluated during 6 months in 15 patients with hypertension associated with mild to moderate kidney failure. After 6 months a significant reduction of SBP and DBP (p < 0.001), with improvement of creatinine clearance and with no adverse effects on ECG, heart rate and routine laboratory tests test, was observed in 3 patients treated with N 20 mg x 2/d + E 10 mg/d + A 50 mg/d and in 8 patients treated with N 20 mg x 3 + E 10 mg x 2, + A 50 mg x 2. Four patients did not respond to this therapy. PMID- 1444162 TI - [The beginnings of the International Cardiology Society]. PMID- 1444163 TI - The diagnosis of diabetes mellitus, including gestational diabetes. PMID- 1444164 TI - Reference values of serum and urine creatinine, and of creatinine clearance by a new enzymatic method. AB - A new, totally enzymatic procedure for the determination of creatinine in serum and urine, using creatinine amidohydrolase, creatine amidinohydrolase, sarcosine oxidase and formaldehyde dehydrogenase is described. The assay was adapted to a discontinuous analyser with each analysis requiring only 20 microL of serum or 3 microL of urine. Analytical recovery of creatinine in serum and urine averaged 100.6%. Within-run and between-run precision studies gave coefficients of variation of 1.1% and 1.8%, respectively, for a serum with mean values of 83 mumol/L (9.4 mg/L) creatinine. Creatinine concentrations in serum and urine were measured by this procedure, in Japanese children and adults. The reference intervals for serum creatinine concentrations in adults were 55-96 mumol/L (6.2 10.9 mg/L) in men and 40-66 mumol/L (4.5-7.5 mg/L) in women, and for urine, 9.46 19.01 mmol/day (1070-2150 mg/day) in men and 6.75-10.61 mmol/day (764-1200 mg/day) in women. The reference intervals of creatinine clearance were 88.0-176.4 mL/min in men and 75.7-173.0 mL/min in women. PMID- 1444165 TI - The steatocrit: an improved procedure. AB - The steatocrit is a simple and easily repeated assay for measuring the fat content of infants' stools. However, we and others have experienced technical difficulties in its use. Three modifications were therefore made to the original procedure: incorporation of a lipid-soluble dye, improved homogenization and a heating step. The modified method was used to measure the stool fat content of young children with and without clinical steatorrhoea. Validation of the modified steatocrit is presented, together with examples of its application to both clinical research and clinical practice. PMID- 1444166 TI - Comparison of post-mortem urinary and vitreous humour organic acids. AB - We have analysed organic acid profiles in 74 samples of post-mortem vitreous humour from the sudden infant death syndrome and compared the profiles to those obtained from the corresponding urine or bladder wall swab. There was a high degree of correlation indicating that vitreous humour analysis in high-risk infants is an appropriate analytical strategy when urine is not available. In our patient sample two infants had evidence of abnormal methylmalonic acid metabolism, one had glyceric aciduria (and elevated levels of vitreous humour glyceric acid), one had evidence of pre-existing liver damage as judged by the presence of 4-hydroxyphenyllactic acid, one had a non-ketotic dicarboxylic aciduria indicating inhibited fatty acid oxidation and two patients had significant long-chain 3-hydroxydicarboxylic acids and evidence of paracetamol ingestion. PMID- 1444167 TI - Investigation of the use of impermeable fluid barriers between pelleted and supernatant enzyme activity in a pseudohomogeneous enzyme immunoassay. AB - We have investigated the feasibility of performing an automated pseudohomogeneous enzyme immunoassay in which a separation step is not apparent to the user. This was achieved using a layer of silicone fluid, which is immiscible with aqueous solutions, as a physical barrier between the pelleted and supernatant enzyme. Initially we produced a manual assay based on the Serozyme T4 assay to demonstrate the feasibility of the approach. This assay showed good precision, parallelism and correlated with 'in house' results on patients' samples. Production of a fully automated assay was made difficult by the design of available equipment but none the less we demonstrated the feasibility of the automated approach by producing a standard curve for T4. PMID- 1444168 TI - New automated nonisotopic immunoassays for free thyroxin: effect of albumin and thyroxin-binding globulin concentrations. AB - Recently, nonisotopic (often automated) immunoassays for measuring serum free thyroxin (FT4) have become available. Though more costly than radioimmunoassays, they are considerably more convenient. We studied the influence of endogenous albumin and thyroxin-binding globulin concentration on five automated, nonisotopic methods of measuring FT4 [Enzymun on ES300 (one-step), Stratus I and II (essentially two-step), Delfia (two-step), and IMx (two-step)] in a mixed patient population. We observed that they (a) are influenced very little by endogenous serum binding proteins and (b) seem to have sufficient within-run precision to justify performing single measurements on patients' specimens. PMID- 1444169 TI - Method comparison--a different approach. AB - The commonly accepted method of analysing data from method comparison studies is regression analysis, a method which has limitations. This study illustrates the use of a graphical presentation of data, the difference plot, which can be used as an alternative to least squares regression analysis. The data from comparison studies performed on five methods were analysed both by Deming's regression analysis, with calculation of the correlation coefficient, and by the difference plot. The results show that in most cases much more relevant information was obtained from the difference plot. PMID- 1444170 TI - Failure to induce reactive hypoglycaemia by drinking whisky and a mixer in Glaswegian alcoholic patients. PMID- 1444171 TI - Evaluation of a new rapid immunometric method for the measurement of the MB isoenzyme of creatine kinase in serum. PMID- 1444172 TI - Performance of the Beckman Diatrac gel electrophoresis method for the measurement of HbA1c. PMID- 1444173 TI - TmP/GFR and ionized calcium in the management of severe hypophosphataemia. PMID- 1444174 TI - Positive interference. PMID- 1444175 TI - Screening for hyperlipidaemia in diabetics. PMID- 1444176 TI - [Insulin resistance and polycystic ovary syndrome]. AB - The causes and consequences of the insulin resistance that accompanies the polycystic ovary Syndrome (PCOS) are still controversial. The hyperandrogenism does not appear any more as a causal factor but on the contrary is likely to be a consequence, via the ovarian effects of hyperinsulinism. These are still not clearly understood in their molecular aspects, but their reality is undoubtful in view of some clinical studies which showed an improvement following by the reduction of hyperinsulinism. Therefore, the aetiopathogenic role of the insulin resistance in PCOS becomes more and more obvious but it cannot be split from the likely implication of the intra-ovarian growth factors, and more especially the IGF 1 which could act synergistically with it. Moreover, the presence of LH seems to be still a pre-requisite to the ovarian action of insulin. The therapeutical incidences of these hypothesis are obvious and should improve in the next future the medical management of PCOS. PMID- 1444177 TI - The influence of oxytocin, vasopressin and their analogues on progesterone and testosterone production by porcine granulosa cells in vitro. AB - Effects of nonapeptide hormones and some of their chemical analogues on progesterone and testosterone production by culture of porcine granulosa cells have been investigated. Oxytocin (0.01-10 IU/ml), arginine-8-vasopressin (0.01-10 micrograms/ml), arginine-8-vasotocin (0.01-10 micrograms/ml) and, in a lesser degree, 2-0-methyl-tyrosine (deamino-1-karba)-oxytocin (0.01-10 micrograms/ml, but no 1-deamino-8-vasopressin (0.01-10 micrograms/ml) stimulated a progesterone surge. Testosterone production was significantly stimulated by oxytocin and inhibited by vasopressin or vasotocin additions. 2-0-methyl-tyrosine (deamino-1 karba)-oxytocin or 1-deamino-8-vasopressin had little or no effect on testosterone secretion. The present results suggest the existence of a direct influence of nonapeptide hormones on porcine ovarian progestagen and androgen production. PMID- 1444178 TI - [Cholecystokinin, neurotensin and corticotropin-releasing factor, three important anorexic peptides]. AB - This paper updates the informations on the three most important anorexigenic peptides: cholecystokinin, neurotensin and corticotropin-releasing factor. Their peripheral and/or central effects on food and water intakes as well as on dietary preferences are detailed. Their mechanisms of action and regulation are examined. This includes the interactions with classical neurotransmitters (norepinephrine, dopamine, etc...) as well as the description of the brain nuclei and neuronal networks involved. Finally, their variations in disturbed feeding behavior (hyperphagia, anorexia) in man or in animal models are reviewed. PMID- 1444179 TI - [Evaluation of nuclear magnetic resonance imaging in tridimensional acquisition in the investigation of prolactin microadenoma]. AB - Twenty one patients with suspected prolactin-secreting microadenoma were evaluated with MRI. MRI is the most sensitive means for detecting focal microadenomas. In these patients who were clinically and endocrinologically considered to harbor a microadenoma, MR detected a focal pituitary signal abnormality in 100% when the patients had not previously taken bromocriptine therapy. On the other hand MR demonstrated a focal abnormality in only 30% of cases when the patients had been on dopamine agonist therapy: the MRI findings in the group of bromocriptine treated patients are not affected by neither the duration and dosage of the therapy or the delay between MR examination and the bromocriptine therapy discontinuation. Among the 9 cases in which MRI did not demonstrate a focal abnormality, MRI was strictly normal in 3 cases only; MR showed a localized expansion of the subarachnoid space in two cases; the pituitary gland was large and round, and had a homogeneous signal in one case; the pituitary gland had a heterogeneous signal in 3 cases. In our study the microadenoma had a high signal intensity on the precontrast T1 weighted sequence in 5 cases. The focal abnormality was not seen on the precontrast MR images in 2 cases. The microadenoma enhanced in 3 cases on the postcontrast three dimensional MR images. This MR technique allows thin section slices (1 mm) and therefore the detection of small focal abnormality of the pituitary gland (2.5 x 3 mm). Thus three points have to the emphasized: a) MRI always detected a microadenoma when the patients had never received a bromocriptine therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444180 TI - [Measurement of impedance of hepatic tissue transformed by pathological process. A preliminary communication]. AB - Intrahepatic impedance was measured using a special electrode in 44 patients, 38 of whom identified abnormalities of the hepatic parenchyma. Impedance values were compared with ultrasound findings and with the histological results of needle biopsy. Impedance was relatively unaffected in the presence of cirrhosis (n = 7) or chronic hepatitis (n = 5). It was markedly decreased in the presence of cysts (n = 4) and of hepatocarcinoma (n = 4). Values were variable in secondary carcinoma of the liver (n = 16). This preliminary study suggests that the measurement of intrahepatic impedance could contribute to the etiological diagnosis of hepatic tumour lesions. PMID- 1444181 TI - [Hepatic amebiasis in a metropolis. Apropos of 9 cases]. AB - From 1981 to 1990 nine patients suffering from amebic liver abscess were under observation at the Tours hospital. Hepatic amebiasis is scarce in France. Most of the subjects have stayed in endemic areas. Most of the time patients are male adults suffering from fever and abdominal pains. In most cases the liver ultrasonography shows a single cut of the right lobe with variable and non specific aspects. Once the diagnosis has been given a metronidazole treatment must be prescribed. The diagnosis will be confirmed by serology reactions. Clinical supervision is essential. The clinical effectiveness of the treatment is spectacular. Comparatively it will take about six months until serology reactions and liver ultrasonography get back to normal. Management of hepatic amebiasis need exceptionally echo-guided percutaneous puncture or surgery. PMID- 1444182 TI - [Gastric metastasis of breast cancer occurring after a cancer-free interval of 30 years]. AB - The authors report the case of a 75-year-old female patient who presented with a deterioration in her general health and epigastralgia 30 years after mastectomy for cancer. The findings of an exhaustive assessment was normal apart from an inflammatory syndrome with hyperleukocytosis and subcardial ulceration, which gave negative endoscopic biopsies. The patient underwent surgery and the total gastrectomy ablation demonstrated that this was a metastasis of a mammary adenoma. Follow-up for two years did not reveal any recurrence. The mean time to the development of gastric metastases of breast cancers is 2 to 4 years. Life expectancy appears to be greater the longer this latency time. The usual blood borne spread explains why endoscopic biopsies may be falsely reassuring, since the first layers to be affected are the serous and submucosal layers. Localized forms may simulate ulcers; nodular forms are more appropriate for curative surgery than the more common infiltrating forms (which resemble linitis). These infiltrating forms are often combined with peritoneal damage and/or extradigestive metastases. PMID- 1444183 TI - [Hiccup caused by epigastric compression in a hemiplegic patient]. AB - The authors report the case of a patient with permanent, refractory hiccup, resistant at all classical treatment methods. Hiccup was due to compression of the epigastric region by the left fist of the patient immobilised by a spastic hemiplegia. Passive mobilisation of the diseased upper limb resulted in the disappearance of hiccup. PMID- 1444184 TI - [Antibiotic-induced diarrhea. Recent data]. PMID- 1444186 TI - [Sphincter preservation in the treatment of rectal cancer]. PMID- 1444185 TI - Anal endosonography. AB - Endosonography of the anal canal is capable of imaging the internal and external sphincters in detail. Abnormalities of thickness may be seen in the internal sphincters and defects in both. The examination is indicated in the investigation of incontinence and anal pain, and may be of value in anal sepsis and malignancy. PMID- 1444187 TI - [Should subdivision of regressive ischemic colitis be envisaged?]. AB - The term "regressive ischemic colitis" is generally accepted and refers to acute hemorrhagic colitis which may occur at any age and recovers spontaneously in most cases, sometimes leaving colonic stenosis due to scarring. Critical analysis of the literature reveals that there is no formal diagnostic criterion for this condition and no real proof that the mechanism is ischemic, particularly in young subjects who have no vascular disorder or hemodynamic triggering factor. The number of clinical, radiological, endoscopic and even histological similarities between regressive ischemic colitis and some forms of infectious colitis, particularly due to enterohemorrhagic E. coli O157:H7 and hemorrhagic colitis due to penicillin derivatives and non-steroid anti-inflammatory drugs is also striking. These observations logically lead us to wonder whether the term "regressive ischemic colitis" does really correspond to a well-defined entity rather than to a group of acute colitis of miscellaneous etiology but with many common features. PMID- 1444188 TI - [Epidemiology and prevention of colorectal cancer]. AB - Colorectal carcinoma is very common in western countries. It is in the front line of malignant pathology in France. The estimated number of new cases is almost 26,000 per year. The role played by diet in the onset of colorectal carcinomas is well established. The majority of studies indicate the protective role played by green vegetables. The role of other factors remains controversial: protective role of fibres, calcium and vitamins and favorizing role of fats, proteins, red meat, alcohol and calorie intake. The role of bile salts in increasing the size of adenomas and their malignant change is accepted. A number of therapeutic trials have involved modifications in bile salt concentrations. These should enable the proposal of a primary prevention strategy. The early detection of carcinomas and the secondary prevention of colorectal carcinoma (by detection of the adenomas which precede a high proportion of carcinomas) are areas of great interest. Detection of occult blood in stools as a mass screening test is currently being evaluated. Methods used to obtain a high participation rate among the population vary from one country to another, but are now well-defined. It will be necessary to wait for 2 years before being able to determine the effect on mortality and an even longer period to evaluate the effect on the incidence of colorectal carcinoma. PMID- 1444189 TI - The role of granulocyte-macrophage colony-stimulating factor in induction of monocytic differentiation of HL-60 cells: synergistic interaction with 1 alpha, 25-dihydroxyvitamin D3 and interferon-gamma in inducing interleukin-1 beta. AB - 1 alpha, 25-Dihydroxyvitamin D3 (D3) (100 nM) and interferon-gamma (IFN-gamma) (100 U/ml) cooperatively inhibited the proliferation of HL-60 cells, and synergistically induced their monocytic differentiation. The growth-promoting effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) (10 ng/ml) was inhibited appreciably by D3 and slightly by IFN-gamma. Despite the clear difference in their effects on growth of HL-60 cells, both IFN-gamma and GM-CSF in combination with D3 induced cell cycle changes, decreasing the number of cells in the S phase and increasing their percentage in the G1/0 phase. GM-CSF alone had no effect on differentiation, but enhanced differentiation induced by D3 distinctly though to a limited extent, and also enhanced monocytic differentiation, including morphological changes of HL-60 cells in the presence of D3 and IFN-gamma. GM-CSF as well as D3 and IFN-gamma induced interleukin-1 beta (IL-1 beta) production by the HL-60 cells, clearly indicating their importance in differentiation of these cells. IFN-gamma and GM-CSF had mutually potentiating effects and induced maximum IL-1 beta production in response to lipopolysaccharide (LPS) in the presence of D3. Thus despite its growth-promoting effect, GM-CSF is a potential inducer of monocytic differentiation of human myeloid leukemia cells, because in cooperation with IFN-gamma it induced monocyte macrophage differentiation of HL-60 cells in the presence of D3. PMID- 1444190 TI - Stimulation by estrogen and progesterone of the in vivo growth of transformed murine Leydig cells only at the limited early phase of growth. AB - B-1 F is a cell line established from estrogen-responsive murine Leydig cell tumor and maintained in vitro. We investigated the effects of steroid hormones on the growth of tumors produced by the inoculation of B-1 F cells into mice. When tumor tissues were transplanted into castrated male mice, injections of estradiol 17 beta (E2) or progesterone shortened the period before tumors became palpable, but did not affect the growth rates of tumors after tumors became palpable. Injections of E2 or progesterone from the time when tumors became palpable did not affect the growth of tumors, and the discontinuation of injections of E2 or progesterone during the middle growth phase showed no effect on the growth of tumors. E2 or progesterone also did not increase the mitotic indices of tumors after they became palpable. E2 and progesterone did not stimulate the proliferation of dispersed tumor cells in vitro. The present results suggested that steroid hormones might exert their actions only at the limited early phase of growth of transplanted steroid hormone-responsive tumors in vivo. PMID- 1444191 TI - Antineoplastic activities and cytotoxicity of 1-acyl and 1,2-diacyl-1,2,4 triazolidine-3,5-diones in murine and human tissue culture cells. AB - 1-Acyl- and 1,2-diacyl-1,2,4-triazolidine-3,5-diones were found to be potent cytotoxic agents in murine and human cancer cell lines, e.g. L1210, P388, Tmolt3, colon adenocarcinoma, Hela cells and glioma. In vivo activity was demonstrated at 8 mg/kg/day against Ehrlich ascites carcinoma growth. In L1210 cells, 1-acetyl-4 phenyl-1,2,4-triazolidine-3,5-dione, 41, reduced DNA synthesis significantly with moderate reduction in RNA synthesis. Enzyme sites in L1210 cells which were markedly affected were m- and r-RNA polymerase, PRPP amidotransferase, IMP dehydrogenase, dihydrofolate reductase, thymidine, TMP and TDP kinases. Kinetic studies suggest the inhibition of rate limiting enzymes in the purine pathway by 41 was responsible for its cytotoxicity. Acute toxicity studies in mice indicated 41 was safe for therapeutic use at 20, 50, and 100 mg/ky/day. PMID- 1444192 TI - An experimental model for the study of thermochemotherapy in vivo. AB - Human melanomas serially passaged in nude mice as xenotransplants were used as models for the study of the effects of thermochemotherapy of human malignant tumours in vivo. Three such melanomas, one (BRO) fast-growing, one (SCH) slow growing, and one (BEL) of intermediate growth rate, were chosen. One group was left untreated as a control, one received chemotherapy (cyclophosphamide), one received hyperthermia, and one a combination of both treatments. In all three tumours, the best results were obtained associating chemotherapy with hyperthermia. The fastest growing tumor responded more than the slower, which responded better than the slowest. This model should prove useful in testing the effectiveness of anticancer agents used in association with hyperthermia. PMID- 1444193 TI - Correlation of drug response in human tumors histocultured in vitro with an image analysis MTT end point and in vivo xenografted in nude mice. AB - We have in this study used the 3-(4,5-dimethyl-2- thiazoyl) -2,5-diphenyl 2-H tetrazolium bromide (MTT) end point in our histoculture drug-response assay. We have previously demonstrated that the formazan crystals formed by MTT reduction by mitochondrial succinate dehydrogenase reflect polarized light and can be measured by pixel analysis in intact tissue. The results described here indicate a total specificity of 93.8% and a total accuracy of 74.6% of the MTT end point for drug response in histoculture correlating with nine different human xenograft tumors grown in nude mice with respect to the in vivo drug response data. This in vitro system allows prediction of positive and negative responses to drugs, with a rate of 70% and 71.8%, respectively. The system described here has potential for clinical use because of the possibility of simultaneous description of the MTT values and heterogeneous response to drugs within individual tumors. PMID- 1444194 TI - Chemosensitivity testing of clinical gastrointestinal cancers using histoculture and the MTT end-point. AB - Three-dimensional histoculture with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl 2H tetrazolium bromide (MTT) end-point was utilized for chemosensitivity testing of 100 clinical gastrointestinal cancers and the results were compared with those obtained with cell-suspension culture with the MTT end-point. Of the 100 surgical specimens, 91 were evaluable using histoculture assay and 66 were evaluable using the cell-suspension assay. When the assay results were compared with historical frequency of clinical response to chemotherapy, the results of the histoculture assay showed a closer correlation than those of the cell-suspension assay. Therefore, the histoculture assay seems to have a higher evaluability rate and a closer correlation with clinical chemosensitivity of gastrointestinal cancers than the cell-suspension assay. PMID- 1444195 TI - Improved immunohistochemical detection of p53 protein in paraffin--embedded tissues reveals elevated levels in most head and neck and lung carcinomas: correlation with clinicopathological parameters. AB - We have analyzed the expression of the p53 tumor suppressor gene in paraffin embedded sections of normal and malignant head and neck and lung tumors by immunohistochemistry using the PAb 1801 monoclonal antibody (MAb). The PAb 1801 does not consistently detect its p53 epitope in tissue fixed in 10% buffered formaldehyde. However, the antibody is effective in AMeX-fixed specimens, thereby permitting the improved morphologic localization of p53 phosphoprotein in paraffin embedded tissue. Of 33 primary head and neck carcinomas analyzed from AMeX-fixed, paraffin-embedded sections, 21 (64%) showed heterogeneous staining with PAb 1801. All 33 normal samples of head and neck tissues were negative. Similarly, 13 out of 20 lung carcinomas (65%) showed heterogeneous staining while none of normal lung tissues were positive. The data indicate a strong positive correlation between p53 detection by PAb 1801 and carcinomas of the head and neck and of lung. However, there was no obvious correlation between p53 staining and the number of involved nodes, the stage of disease or the degree of differentiation in these carcinomas. PMID- 1444196 TI - Extensive liver metastasis from human colon cancer in nude and scid mice after orthotopic onplantation of histologically-intact human colon carcinoma tissue. AB - Clinically-relevant animal models of human cancer are greatly needed for the study of human cancer biology and the development of new cancer therapeutics and diagnostics. We report here that by orthotopically transplanting histologically intact human colon cancer to the colon of the immunodeficient nude and scid mouse mutants that extensive local growth and liver metastases occur consistently even after extensive in vivo orthotopic passage. We demonstrate that the liver metastases arise by hematogenous spread. The models described in this report for human colon cancer should prove useful for individual cancer patients as well as for basic and applied studies to develop improved treatment. PMID- 1444197 TI - A patient-like metastasizing model of human lung adenocarcinoma constructed via thoracotomy in nude mice. AB - A new nude-mouse metastasizing orthotopic transplant model of human adenocarcinoma of the lung is described. Histologically-intact human A549 adenocarcinoma lung tumors were transplanted to the left lung of nude mice via a thoracotomy procedure we have developed. The transplanted tumors grew extensively locally and metastasized to the opposite lung, lymph nodes and other clinically relevant sites. The results described indicate the model developed could have clinical relevance and contrast with models of the A549 lung adenocarcinoma constructed orthotopically with injections of cell suspensions which result in low metastatic potential. PMID- 1444198 TI - Augmentation of antineoplastic effects by the combination of recombinant human tumor necrosis factor and mitoxantrone on primary culture of human ovarian cancer cells. AB - Recombinant human tumor Necrosis Factor (rHuTNF) produced dose-dependent cytotoxicity against human ovarian cancer cells, OSC and OMC, obtained from fresh ascites. A combination of rHuTNF and the topoisomerase II inhibitor, Mitoxantrone, produced dose-dependent synergistic cytotoxicity on OSC and OMC cells. When OMC cells were incubated simultaneously for one hour with rHuTNF and Mitoxantrone, increased numbers of DNA single-strands breaks were produced. rHuTNF alone did not induce DNA single-strands breaks. These data are consistent with a role for topoisomerase-linked DNA lesions in the rHuTNF mediated potentiation of killing cells by Mitoxantrone. PMID- 1444199 TI - Clinical stage I and II endometrial carcinoma: multivariate analysis of prognostic factors. AB - In 221 patients with FIGO stage I and II endometrial carcinoma, the impact on survival of age at diagnosis, menopausal status, FIGO stage, myometrial invasion, tumor grade and histology was evaluated by univariate and multivariate analysis. At a median follow-up of 50 months (range 45-210), 42 patients had died, and therefore overall survival was 81% (179/221). Univariate analysis showed that age, menopausal status and histology did not influence survival, whereas FIGO stage, myometrial invasion and tumor grade were important prognostic factors. Multivariate analysis showed that tumor grade had a significant and independent impact on survival and confirmed that FIGO stage is the most important parameter influencing survival. PMID- 1444200 TI - Enhanced chromosomal fragility in neuroblastoma: correlation with poor prognosis. AB - In a previous study we demonstrated spontaneous fragility and hypersensitivity to fragile site induction by aphidicolin in lymphocytes from some neuroblastoma patients and their parents. Here we report data based on a total of 40 patients and 37 families. Possible correlations between higher sensitivity to aphidicolin and a variety of personal and clinical characteristics were verified. Patients with a poor prognosis generally proved to be more susceptible to fragile site induction. PMID- 1444201 TI - Relationship between pi-electron distribution and anticancer activity of benzo[a]phenothiazines. AB - In order to study the correlation between the anti-tumor activity of benzo[a]phenothiazines and the electron densities, the Huckel orbital method and modified-neglect-of-diatomic overlap (MNDO) orbital method were used. 9-Methyl 12H-benzo[a]phenothiazine (2), which showed the most potent anticancer activity among benzo[a]phenothiazines, had the highest charge of nitrogen atom (QN), L region (QL) and M-region (QM) in the molecule. The other derivatives, which showed weaker anticancer activity, had a much reduced value of these charges (QN, QL, QM). The data suggest that stability of pi-electron in 1 benzene ring and 1 naphthalene ring in the benzo[a]phenothiazine skeleton might be responsible for the induction of anticancer activity. PMID- 1444202 TI - Complications of total gastrectomy for gastric cancer--with special reference to anastomotic failure. AB - We have reviewed the data on patients totally gastrectomized for gastric cancer during a 12 year period at our hospital. Our findings are summarized, as follows: 1. Advanced cases (stage III, IV) accounted for 85.4% (276/323) of them. Combined resection of other organs was performed on 87.6% of them. Twelve percent of the patients had peritoneal dissemination of P2 or higher grade and 5.9% hepatic metastases of H1 or higher grade. 2. Roux-en Y anastomosis was the most frequent (83.3%) reconstructive procedure. There were a total of 124 episodes of postoperative complications in 76 cases (23.5%). The lung and liver were often involved. Twenty-four cases (7.4%) suffered from postoperative anastomotic failure, which developed commonly at the site of oesophago-jejunostomy. Major leakage from this portion was the cause of death in 62.5% of the cases. The mortality rate was not notably different between the groups subjected to different reconstructive procedures or between the autosuture group (using an EEA stapler) and the hand suture group. The incidence of death due to the surgical intervention was 1.9%. 4. The 5-year survival after total gastrectomy was 25.2%, which was not necessarily satisfactory. However, it was significantly higher in the curative resection group than in the non-curative resection group (40.2% vs 3.3%). PMID- 1444203 TI - An oligomer complementary to the 5' end region of MDR1 gene decreases resistance to doxorubicin of human adenocarcinoma-resistant cells. AB - Acquired resistance to doxorubicin and other anti-cancer drugs is generally dependent on gene amplification of a specific nucleotide sequence, the MDR1 gene. Verapamil, cyclosporin and other drugs have been used to circumvent the resistance in experimental models in vitro and/or in vivo. We have attempted to reverse the MDR phenotype by treating human adenocarcinoma resistant cells with 20 mers of synthetic unmodified oligodeoxynucleotide MDR1 antisenses. Five ODNs towards different mRNA regions and three different schedules of ODN antisense administration were tested. We found that FCS concentration greatly influenced the stability of ODN, whereas heat-inactivated FCS had no effect. The kinetics of ODN cellular uptake suggest the presence of a saturable receptor. Among the five antisense ODNs used, the most efficient was the oligomer (ODN-1) complementary to 20 bases upstream of the AUG initiation codon. No effect was observed with antisense complementary to the nucleotide binding sites. Administration of ODN-1 every 12 hr for 72 hr partially reversed the MDR phenotype. Approximately 60% of the cells lost their resistance to doxorubicin and did not form colonies in the presence of the drug. The MDR1 mRNA was transiently down-regulated so that the level of gp170 was slightly reduced. The incomplete switch off of MDR1 gene expression may be ascribed to the large abundance and great stability of MDR1 messenger RNA. Moreover, the inactivity of the two ODNs complementary to the NBS protein domains suggests that translation inhibition is ineffective. It is likely that ODN-4 and ODN-5 complement a large number of mRNAs competing for duplex formation, because these sequences are highly conserved among many proteins. PMID- 1444204 TI - A decision support system for predicting a recurrence of breast cancer; a prospective study of serum tumour markers TAG 12, CA 15-3 and MCA. AB - The aim of the present study was to evaluate the clinical value of the preoperative serum tumour markers TAG 12, CA 15-3 and MCA in predicting a recurrence of breast cancer patients. The sensitivity of the TAG 12 test was 54%, that of the CA 15-3 test 15% and that of the MCA test 15% in predicting a recurrence of breast cancer. The most important predictor of breast cancer recurrence was TAG 12. In order to evaluate the contributions of different tumour marker serum test, a stepwise discriminant analysis was carried out. The discriminant function (DF) is DF = TAG 12 x 0.061 - CA 15-3 x 0.1336 - 0.396. The sensitivity of the DF in detecting recurrence of breast cancer was 63% with a specificity of 90% and an efficiency of 75%. In conclusion, the results indicate that a new tumour marker TAG 12 is superior to CA 15-3 and MCA in predicting breast cancer recurrence. In this study the discriminant function including TAG 12 and CA 15-3 was superior to single preoperative tumour marker tests. The results speak for the use of a decision support system to aid in predicting a recurrence of breast cancer. PMID- 1444205 TI - A novel triple label method validates the double label technique of defining cell cycle kinetics in HL-60 cells. AB - HL-60 cells were sequentially labeled with the thymidine analogues iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU). The labeling index (LI), the duration of S-phase (Ts) and the total cell cycle time (Tc) were measured immediately. It was therefore possible to predict the next time when the single versus double labeled cells would re-enter the S-phase. In our study, the Tc was calculated to be 20 hours. The third label, tritiated thymidine (3HTdR), was introduced at the predicted time of 20 hours to confirm the validity of the previously calculated Tc. The actual percentage of cells which were labeled by (3HTdR) was very similar to the predicted value. We conclude, therefore, that the calculated cell cycle time correlated well with the actual cell cycle time, at least in a controlled in vitro culture system. This novel triple label method validates our double-label technique developed for cell cycle measurements. PMID- 1444206 TI - Polyamine deprivation enhances antitumoral efficacy of chemotherapy. AB - We reported previously that polyamine deprivation by feeding a polyamine deficient diet combined with gastrointestinal tract decontamination and polyamine oxidase inhibition considerably enhanced the antitumoral effect of DFMO, a selective inhibitor of ornithine decarboxylase. The combination of polyamine deprivation and administration of well established cytotoxic drugs was expected to improve further the antitumoral effect of polyamine deprivation in Lewis lung carcinoma grafted in mice. Simultaneous treatment, i.e. administration of the cytotoxic drugs during the polyamine deprivation regimen, reduced tumor growth, but enhanced toxic effects. By alternating treatment and polyamine deprivation (1st day methotrexate (1.7 mg/kg), 2nd day cyclophosphamide (90 mg/kg), 3rd day vindesine (0.25 mg/kg), followed by five days of polyamine deprivation), tumor growth was reduced by 90% and an increase of 64% in the survival time of the animals was observed, demonstrating that a significant enhancement of the efficacy of chemotherapy was achieved without concomitant enhancement of toxic effects. PMID- 1444207 TI - A comparison of biochemical and immunohistochemical assessment of EGFR expression in ovarian cancer. AB - The presence of epidermal growth factor receptor (EGFR) was determined both by immunohistochemistry and ligand binding assay in 118 samples from 96 cases of ovarian cancer. EGFR was present in 47.5% of tumours biochemically and in 39.8% of tumours analysed immunohistochemically. The concordance rate for the techniques varied between 40% in endometrioid carcinomas to 85.7% in undifferentiated carcinomas with an overall concordance of 69.5% (p < 0.001). There was no significant difference between the presence of the high, low or high plus low affinity receptor components and tumour immunoreactivity. Although the ligand binding assay is more sensitive than immunohistochemistry for detecting the epidermal growth factor receptor, some cases are positive only on immunohistochemical screening. We would recommend that both techniques should be performed in prospective studies in order to elucidate the role of EGFR expression in ovarian cancer. PMID- 1444208 TI - Agrimoniin, an antitumor tannin of Agrimonia pilosa Ledeb., induces interleukin 1. AB - The induction of interleukin-1 (IL-1) by agrimoniin, a tannin of Agrimonia pilosa Ledeb., in human peripheral blood mononuclear cells (PBMC) in vitro and in mouse adherent peritoneal exudate cells (PEC) in vivo was studied. A significant amount of IL-1 beta in the culture supernatant of the human PBMC stimulated with agrimoniin was detected with an enzyme-linked immunoadherent assay. Agrimoniin induced IL-1 beta secretion dose- and time-dependently. The adherent PEC from mice intraperitoneally injected with agrimoniin (10 mg/kg) also secreted IL-1 4 days later. These results suggest that agrimoniin, a plant tannin, is a novel cytokine inducer. PMID- 1444209 TI - Immunomodulating effects of the hydrolysis products of formosanin C and beta ecdysone from Paris formosana Hayata. AB - Formosanin C (PF-3, I), a diosgenin glycoside with four sugars isolated from Paris formosana Hayata as main constituent, significantly showed immunomodulating effects on the proliferative response of mouse lymphocytes to concanavalin A (Con A). The partialy hydrolysis products of formosanin C, dioscin (II) and prosapogenin A of dioscin (III), also increased 3H-thymidine incorporation of Con A-stimulated lymphocytes maximally at 0.01 micrograms/ml, whereas formosanin C did so at 0.0001 micrograms/ml. However, trillin (IV) and diosgenin (V) obtained from the partial hydrolysis of formosanin C had no effects on these immune responses. Evidently, the immunomodulating activities increased in the order of increasing polarity. Probably the solubility in water was a factor. This demonstrated that the sugar moiety in the structure of formosanin C (I) displays a very important pattern for the effect on the proliferative response of mouse lymphocytes to Con A. On the other hand, these hydrolysis products at higher concentrations of 1 and 10 micrograms/ml reduced the cytotoxic effects on spleen cells as compared with formosanin C. The other constituent, beta-ecdysone (VI) isolated from the stems of Paris formosana Hayata also increased 3H-thymidine incorporation of Con A-stimulated splenocytes. At the concentration of 0.001 micrograms/ml, the stimulation index of beta-ecdysone (2) is higher than that of formosanin C (1.65), and at the concentration of 100 micrograms/ml, beta-ecdysone had no cytotoxicity for normal spleen cells whereas formosanin C at the lower concentration of 10 micrograms/ml showed cytotoxicity. Based on this study, beta ecdysone (VI) is therefore a better immunomodulator than formosanin C. PMID- 1444210 TI - Opposite effects of dehydroepiandrosterone on the growth of 7,12 dimethylbenz(a)anthracene-induced rat mammary carcinomas. AB - The effect of dehydroepiandrosterone (DHEA) (2 mg, twice daily p.o.) on the growth of the dimethylbenz (a) anthracene (DMBA)-induced mammary carcinoma was studied in intact and ovariectomized adult female rats. DHEA treatment stimulated the tumor growth in ovariectomized animals. Conversely, the tumors of intact rats treated with DHEA progressed to a lesser extent than those of intact untreated animals (p < 0.01). Plasma levels of DHEA were higher in DHEA-fed than in untreated animals (p < .01), whereas E2 concentrations were unchanged after DHEA administration. Estrogen receptor (ER) concentrations in tumor tissue of ovariectomized animals given DHEA were no different form those found in intact rats, whereas ER were undetectable in untreated ovariectomized rats. The data indicate that DHEA stimulates the growth of DMBA-induced mammary tumors in ovariectomized rats, while it reduces the tumor progression in intact animals. PMID- 1444211 TI - Cytogenetic and corresponding flow cytometric DNA analysis of renal cell neoplasms. AB - Results of flow cytometric DNA content and cytogenetic analyses of six neoplasms representing the spectrum of the morphologic subtypes of renal cell neoplasms are compared. Flow cytometric determinations of DNA diploidy and near diploidy in two renal cortical neoplasms correlated with modal chromosome numbers; however, in three of four neoplasms with a highly aneuploid DNA content, the modal chromosome numbers indicated diploidy or near-diploidy. Our data suggest that the short-term culture conditions used in cytogenetic analysis may favor growth of cells with diploid or near-diploid DNA content. This may explain the discrepancy frequently observed between results obtained using flow cytometry and karyotyping after short-term culture. We also observed (1) abnormalities in the short arm of chromosome 3 in all three nonpapillary neoplasms, (both clear and granular cell types); (2) aberrations in chromosomes 3 and 17 in the two papillary tumors; and (3) normal chromosome 3 in the presence of various random karyotypic anomalies including telomeric associations and a pseudo-diploid modal chromosome number in the only oncocytic neoplasm studied. PMID- 1444212 TI - Effects of high and low single dose irradiation on glioma spheroid invasion into normal rat brain tissue in vitro. AB - The effects of radiation on direction on directional migration in monolayer cultures and brain tissue invasion by two glioblastoma cell lines (D-54 MG, D-247 MG) were investigated. The Leksell Gamma Unit was the radiation source and invasion was registered in an in vitro invasion assay developed in our laboratory. As tumor spheroids and brain tissue aggregates were treated simultaneously in cocultures; the effects of radiation on the interaction between the two tissues could be investigated. Tumor spheroids from both cell lines retained their ability to invade and destroy normal brain tissue, even after irradiation with 47.6 Gy. However, while the D-54 MG tumor spheroids showed a dose-dependent reduction of invasion, tumor spheroids from the D-247 MG cell line did not. In addition, radiation produced a dose dependent inhibition of directional migration of cells from D-54 MG spheroids. A similar significant inhibition of directional migration was found in D-247 MG, but it was not dose dependent. Transmission electron microscopy revealed a loosening of the neuropil in the brain tissue of irradiated cocultures. However, this structural change did not seem to affect the invasiveness of the tumor. In this preliminary study, irradiation could not prevent invasion of two different glioblastoma cell lines into fetal rat brain tissue. Further studies using the same technique may help to understand the influence of ionizing radiation upon the invasion process in gliomas. PMID- 1444213 TI - Clinical, histological and quantitative prognostic factors in cutaneous malignant melanoma. AB - A retrospective study including 55 cutaneous melanoma patients with 9.5 years follow-up was carried out to assess the significance of various prognostic factors. The histological samples were evaluated according to Clark's and Breslow's classifications and six nuclear features were measured by interactive morphometry. Mitotic activity was assessed by two different methods: mitotic activity index (MAI) and volume corrected mitotic index (M/V index). The overall disease-related five-year survival of patients was 76.4%. TNM stage (p = 0.0001), sex (p = 0.0024), M/V index (p = 0.003), standard deviation of nuclear form factor (p = 0.023), MAI (p = 0.02), shortest nuclear axis (p = 0.023) and Breslow's classification (p = 0.044) predicted survival in univariate analysis. A multivariate analysis including clinical, histological and morphometric features pointed the Clark's classification as the most important predictor of survival (p = 0.002), while the other variables included had no independent prognostic value. The prognostic importance of mitotic indices and morphometric features is clearly a subject for further studies in superficial melanomas. PMID- 1444214 TI - Effects of dietary fatty acid composition on tumor growth and metastasis. AB - Unsaturated fatty acids of the n-6 and n-3 class have been shown to affect tumor growth and metastasis. The very long chain polyunsaturated fatty acids of the n-3 family, e.g. eicosapentaenoic acids (C20:5n-3) and docosahexaenoic acids (C22:5n 3), have an inhibiting effect on tumor growth. Metastasis is promoted by n-6 polyunsaturated fatty acids, e.g. linoleic acid (C18:2n-6) and gamma-linolenic acid (C18:3n-6). The mechanisms of promotion and inhibition are described in the present review. The mechanisms of lipid peroxidation, which appears to be an important factor in the inhibition of tumor growth, are discussed. Lipid peroxidation is induced by polyunsaturated fatty acids involving autoperoxidation a.o. and the enzymes cytochrome P450, cyclooxygenase and lipoxygenase. In tumor cells these enzymes are decreased in activity but at present the reason for this reduction is not known. Lipid peroxidation products such as hydroxyeicosatetraenoic acids (HETES), hydroperoxy eicosatetraenoic acids (HPETES) and malondialdehyde may have a regulating effect on DNA duplication enzymes (e.g. polymerases). Prostaglandin synthesis in tumor cells and macrophages is also affected by polyunsaturated fatty acids. The fish oil fatty acids are known to reduce prostaglandin synthesis by competing with arachidonic acid for the enzyme cyclooxygenase. However, fish oil fatty acids have an antagonistic effect on cyclooxygenase. Polyunsaturated fatty acids also have an effect on the immune system and particularly on macrophages. Macrophages, but also T-cells and B-cells, are inhibited by prostaglandins such as PGE2, while immunosuppressor cells are stimulated by PGE2. PMID- 1444215 TI - Growth effects of tamoxifen on Lovo colon carcinoma cells and cultured cells from normal colonic mucosa. AB - The growth effects of tamoxifen (TAM) were studied using normal and malignant colonic epithelial cells. Addition of TAM (0.8 to 10 microM) to cultured normal human colon epithelial cells and Lovo colon adenocarcinoma cells produced a dose response decrease in growth of 42 to 76%. Histamine (1 to 10 microM) did not affect cell growth and did not negate the TAM effect. Calmodulin (2 micrograms/ml) totally blocked growth inhibitory effects of a calmodulin antagonist, trifluoperazine (10 microM), but did not block the TAM inhibitory effect. These data suggest that antiestrogen binding sites (AEBS) may play an important role in the growth-inhibitory effects of TAM on colon cells. Competition with estrogen and antagonism with histamine or calmodulin do not appear to be significant in this regard. PMID- 1444216 TI - Histological and quantitative prognostic factors in transitional cell bladder cancer treated by cystectomy. AB - A cohort of 103 transitional cell bladder tumours (TCC) treated by cystectomy was followed up over 9 years. Patients treated with radiation and cystectomy had a more unfavorable prognosis than patients treated by cystectomy alone (p < 0.0001). Old patients had an unfavorable prognosis after cystectomy, whereas none of the patients under the age of 50 died of TCC after cystectomy (p = 0.027). WHO grade (p = 0.002), high mitotic rate (p = 0.012) and nodular growth pattern (p = 0.004) were signs of ominous disease outcome in univariate survival analysis. Dense inflammatory cell infiltrates in the tumour itself or around invasive tumour cells were signs of good prognosis after cystectomy (p = 0.001) in a multivariate analysis. Clinical stage or nuclear morphometric factors had no independent prognostic value after cystectomy. The results clearly show that the intrinsic malignancy of TCC and host defence mechanisms together determine the prognosis after cystectomy. The evaluation of malignant features in TCC alone is an insufficient means of predicting prognosis in invasive TCC and the analysis of host immune response should be included in the prognostic evaluation. PMID- 1444217 TI - DNA ploidy, S-phase fraction and mitotic indices as prognostic predictors of female breast cancer. AB - DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour diameter (p < 0.001), M/V index (p = 0.006) and the year of treatment (p = 0.08) were independent predictors. The results show that tumour diameter, pN status and proliferative activity of cancer cells are important prognostic factors in breast cancer. Of the proliferation indices, M/V index and SPF are equally powerful predictors, and the use of M/V index is advocated due to simplicity of the assessment. PMID- 1444218 TI - Southern travelling habits with special reference to tumour site in Swedish melanoma patients. AB - Southern travelling habits were recorded for 127 melanoma patients from southern parts of Sweden (the 56th latitude), 55 thyroid cancer patients, 100 non Hodgkin's patients and 794 healthy controls from the same region. Melanoma patients were found to travel significantly more often south of the 45th latitude, as compared with patients with non-Hodgkin's lymphoma or thyroid carcinoma (RR = 2.2 for a difference of + 10 trips), and with the healthy controls (RR = 1.4 for a difference of + 10 trips). Considering men and women separately, the difference was significant only for men. Patients with melanoma had a higher educational level than the tumour controls and the healthy controls (p < 0.001 and p < 0.001 respectively). There was a significant correlation between high travelling frequency and high education. An increased risk related to southern travelling was present for patients with melanoma on the extremities and head and neck, as well as for patients with truncal melanoma. These findings support the concept that acute exposure to sunburn may be a risk factor for malignant melanoma. PMID- 1444219 TI - Thermal effects on DNA synthesis in bone marrow cells of patients with acute myeloblastic leukemia. AB - It has been known that thymidylate synthetase (TS) and thymidine kinase (TK) are DNA-synthesizing enzymes via the de novo and salvage pathways, respectively, in pyrimidine metabolism, and an immunological method using a monoclonal antibody to bromodeoxyuridine (BrdU) is useful for the detection of S-phase cells. We investigated the effects of hyperthermia on DNA synthesis in bone marrow cells obtained from patients with acute myeloblastic leukemia. TK isozymes in bone marrow cells of patients with acute myeloblastic leukemia were separated into two types, i.e., fetal type isozyme in cytosolic cell fraction and adult type isozyme in mitochondrial cell fraction. Heating at over 43 degrees C as a hyperthermia markedly suppressed enzyme activity of fetal type TK isozyme and number of S phase cells labelled with BrdU, but not activities of adult type TK isozyme and TS. These results indicate that hyperthermia may regulate the proliferation of S phase cells by the suppression of salvage synthesis of DNA. PMID- 1444220 TI - Modulation by l-leucovorin of 1-hexylcarbamoyl-5-fluorouracil antitumor activity on human gastric and colon carcinomas serially transplanted into nude mice. AB - Experimental biochemical modulation of 1-hexylcarbamoyl-5-fluorouracil (HCFU) with l-leucovorin (LV) was carried out using human gastric (H-111) and colon (Co 4) carcinoma xenografts serially transplanted into nude mice. Thirty-five or 70 mg/kg HCFU dissolved in 0.2 ml of 1% hydroxymethyl cellulose was administered po daily for 3 weeks except Sundays, and 50, 100, 200 or 300 mg/kg LV dissolved in 0.2 ml physiological saline was administered po 30 min before administration of HCFU. The biochemically modulated antitumor activity was evaluated in terms of actual tumor weight, the relative mean tumor weight and the degree of inhibition of thymidylate synthetase (TS) in the tumors at the end of the experiments, assayed according to the method of Spears et al. Although 35 mg/kg HCFU was ineffective against gastric carcinoma H-111, combination with 200 or 300 mg/kg LV resulted in a positive antitumor effect of HCFU on this strain without any increase of side effects in terms of body weight loss and mouse mortality. The colon carcinoma strain Co-4 showed marginal sensitivity to HCFU (35 mg/kg) alone, but 50 or 100 mg/kg LV modulated the antitumor activity of HCFU on Co-4 to produce a significant positive effect without any increase in toxicity, and HCFU administered with 100 mg/kg LV was more effective than the maximum tolerated dose of HCFU (70 mg/kg) alone. The TS inhibition rate was closely related to the biochemical modulation of HCFU antitumor activity by LV, suggesting that the modulation involves an increase of the ternary complex of TS, 5,10-methylene tetrahydrofolate from LV and 5-fluorodeoxyuridine 5'-monophosphate (FdUMP). Combination of HCFU and LV is therefore thought to be useful in increasing the antitumor activity of HCFU on gastrointestinal carcinomas without enhancing its toxicity. PMID- 1444221 TI - Prognostic factors in node positive primary breast cancer patients treated with adjuvant CMF. AB - The influence of various patient and disease-related parameters on survival (S) and disease-free survival (DFS) in 217 node positive primary breast cancer patients treated with surgery followed by adjuvant i.v. cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) was evaluated by univariate and multivariate analyses. Five year actuarial S and DFS were 73.3% and 54.8%, respectively. Univariate analysis revealed that patient age, number of involved axillary nodes and ER status had a significant impact on both S and DFS. PgR positive tumors had improved DFS but no S difference was observed. Menopausal status predicted S but not DFS. Primary tumor size and CMF-induced amenorrhea did not predict disease outcome. Multivariate analysis demonstrated that only degree of nodal involvement and PgR status had independent significant impact on prognosis. Both S and DFS are significantly influenced by the number of involved nodes, whereas improved DFS but not S was evident in patients with PgR positive tumors. PMID- 1444222 TI - Effect of calcium-modifying agents on the growth of human gastric carcinoma cells in vitro. AB - The antiproliferative effects of various calcium-modifying agents were investigated in human AGS gastric carcinoma cells in culture. Variation of the extracellular calcium concentration, achieved by addition of calcium to the growth medium or binding of calcium to the calcium-chelating agent EDTA, appeared to have little influence on growth of the tumor cells. In contrast, the calcium antagonist verapamil, the calcium ionophore A 23.187 and the calmodulin antagonist W 7, agents supposed to interfere with the regulation of the intracellular calcium concentration, all exerted marked growth inhibiting effects. Our results provide evidence for an important role of intracellular calcium-dependent mechanisms in growth regulation of the human gastric adenocarcinoma cell line AGS. PMID- 1444223 TI - Proliferative effect of dexamethasone on a human glioblastoma cell line (HU 197) is mediated by glucocorticoid receptors. AB - The relationship between Dexamethasone proliferative activity and the presence of glucocorticoid receptors was studied on a human glioblastoma cell line (HU 197). For this purpose, the 17 beta-Carboxamide steroid DXB, a glucocorticoid antagonist that competes with Dexamethasone for binding to the intracellular glucocorticoid receptor but does not trigger the glucocorticoid effect, was used. Concurrent treatments with Dexamethasone and DXB caused an inhibition of the proliferative effect obtained by Dexamethasone. The results obtained demonstrated that the Dexamethasone activity on cell proliferation is a specific receptor mediated effect. PMID- 1444224 TI - Synergistic cytotoxic effects of tumor necrosis factor, interferon-gamma and tamoxifen on breast cancer cell lines. AB - The combined effects of recombinant human tumor necrosis factor (TNF), interferon gamma (IFN) and tamoxifen (TAM) on the proliferation of human breast cancer cell lines were investigated. In estrogen receptor positive MCF-7 cells, relatively resistant to TAM or TNF, cytotoxicity significantly increased in combinations of TNF and IFN, and of a cytokine and TAM. The cytotoxicity of TNF increased when cells were pretreated with IFN, but not vice versa. Sequential treatment with IFN following TNF and TAM also exhibited significant antiproliferative effect on both cell lines. The combined or sequential cytokines and TAM treatments are possible modalities to overcome breast cancers unresponsive to endocrine treatment. PMID- 1444225 TI - Cytotoxic action of cyclosporins on human tumor cell lines is not dependent on immunosuppressive activity. AB - The cytotoxic activity of cyclosporin A (CsA) and the three non-immuno suppressive CsA analogues B3-243, WO-039 and B3-665 were studied in tumor cell lines representing both classical and atypical forms of multidrug resistance (MDR): T-ALL GM3639 L100 cells selected for vincristine (vcr) resistance and displaying characteristics of classical MDR, including P-glycoprotein (pgp) expression and increased drug efflux which can be inhibited by pgp blockers (e.g. verapamil), and U-1285/ADR, a small cell lung cancer (SCLC) cell line selected for doxorubicin resistance which lacks pgp, is insensitive to pgp-blockers and shows cross resistance to cis-platinum. At 1 micrograms/ml CsA was the most active agent in reversing Vcr resistance in L100 cells followed by B3-243 and WO 039, with no effect of B3-665. Parental LO cells were only marginally sensitized to Vcr by these agents. No reversing effect of any cyclosporin was observed in the U-1285/ADR or its parental cell line. Compared to LO cells, L100 cells showed a marked hypersensitivity to CsA > B3-243 > WO-039 with B3-665 being inactive. No collateral sensitivity was observed for cyclosporins in U-1285/ADR cells. Although of different magnitude, the pattern of cytotoxic activity for the different cyclosporins alone closely parallelled that of L100 cells for U-1285, U1285/ADR and LO cells. The results indicate that not only the collateral sensitivity in classical MDR but also the cytotoxic actions of cyclosporins per se on tumor cells alone are independent of immunosuppressive activity. The results also suggest a structure-activity relationship for cyclosporin-induced cytotoxicity similar to, but independent of, MDR reversing activity. PMID- 1444226 TI - Modulation of DNA damage by vitamin A in developing Sprague-Dawley rats. AB - Prenatal and neonatal Sprague-Dawley rats were given a diet deficient in or with an excess of Vitamin A and at the age of 55 days female progeny were treated with a single i.g. dose of 80 mg/kg DMBA or 50 mg/kg MNU. Under these experimental conditions it was found that the exposure of perinatal rats to a diet containing an excess of Vitamin A caused a decrease in the amount of DMBA- and MNU-induced DNA damage in the mammary gland and the liver of the female offspring. When diets were deficient in Vitamin A there was a dual effect in terms of DNA damage detected in the same organs, namely DMBA caused an amount of DNA damage comparable to controls, while the extent of DNA damage induced by MNU greatly increased in both organs. These results indicate that Vitamin A can permanently change the sensitivity of adult progeny to chemically induced DNA damage when it is given to pregnant and lactating females. PMID- 1444227 TI - Relation between the hormonal and epidemiological aspects of ovarian cancer patients in Japan. AB - We compared the hormonal and epidemiological aspects of ovarian cancer patients in search of the etiology of this neoplasia. Case-control studies of Japanese women with and without cancer were conducted in parallel, with regard to both the excretion of 14 urinary steroids and the pertinent physical and physiological parameters. The results obtained are as follows: 1) premenopausal ovarian cancer patients before and after radical ovariectomy and postmenopausal-postoperative patients were associated with a specified steroid deviation profile characterized by a combination of general depression of androgens, progestins and corticosteroids with sole rescue of tetrahydrocortisol (THF) in urine. 2) The deviation profile of postmenopausal-preoperative cancer patients was distinguished from the 3 partner profiles by its preservation of normalcy in the excretions of androgen and progestin in urine. 3) Ovarian cancer patients were associated with growth retardation, when compared with urban healthy controls and patients with either breast cancer or endometrial cancer by the age-matching method. Ovarian cancer patients were also less fertile than age-matched normal controls, and were as infertile as age-matched patients with either breast cancer or endometrial cancer. 4) Epidemiological evidence was presented to suggest that the incidence of ovarian cancer in Japan was increasing in parallel with the recent increase of social tension in Japan. The possible relevance of the hormonal characteristics of ovarian cancer patients to both the epidemiological characteristics of the same cancer patients and the genesis of this neoplasia is discussed in the light of the 2-step carcinogenesis theory. PMID- 1444228 TI - Does surgical stress cause tumor metastasis? AB - The purpose of this study was to test the validity of our working hypothesis that the stress of radical surgery may affect the prognosis of a cancer patient by precipitating hematogenous tumor metastasis, and that enhancement of this type of tumor metastasis is mediated by an increase of glucocorticoid activity that is induced in a cancer patient by surgical stress. Practically, we looked for the presence of glucocorticosteroid excess in cervical cancer patients in the course of radical surgery, and also tested the possible impact of glucocorticoid excess on the development of tumor metastasis in mice with i.v. inoculated Ehrlich ascites clone 1 tumor cells. The results obtained indicated that: 1) a state of glucocorticoid excess was observed in cancer patients at an early stage of postoperative convalescence. 2) Development of lung metastasis of blood-borne Ehrlich ascites tumor cells was facilitated in mice by hydrocortisone pretreatment--a substitute for surgical stress conditioning. 3) In the enhancement of lung metastasis, the hormone was found to induce constriction of the lung capillary lumen on the one hand, and acceleration of microvillus growth of the tumor cell surface on the other hand two morphological changes that may facilitate intrapulmonary retention of tumor cells. 4) Cyclophosphamide, as tested in a series of adjuvant chemotherapy experiments, was effective in either retarding or arresting the progress of tumor metastasis in hydrocortisone conditioned mice. The possible impact of surgical stress on the spread of blood borne tumor cells to the lung and liver, as well as on the therapeutic effect of cyclophosphamide for the prevention of postoperative micrometastasis, is discussed in the light of glucocorticoid actions on its target tissues. PMID- 1444230 TI - Nucleolar organiser regions (AgNORs) related to histopathological characteristics and survival in prostatic adenocarcinoma. AB - The number of silver stained nucleolar organiser regions (AgNORs) was assessed in biopsy specimens of 78 patients with prostatic adenocarcinoma followed up for a mean of 15.6 years. The number of Ag-NORs was related to histological features, clinical stage, DNA ploidy, S-phase fraction (SPF) and clinical outcome. In 31/36 (86%) of grade I tumours on average less than 3.5 AgNORs/nucleus were present, whereas of grade III tumours 8/18 (44%) showed usually more than 3.5 Ag NORs/nucleus (p = 0.0163). The number of Ag-NORs was significantly related to mean nuclear area (NA) (p = 0.017) and to SD of nuclear area (p = 0.05). The Ag NORs were not related significantly to clinical stage, perineural infiltration, lymphatic infiltration, DNA ploidy, SPF, G2 fraction or M/V index, although there was a clear trend between the variables. In survival analysis, the degree of lymphatic infiltration (LI) (P = 0.009) predicted survival, whereas AgNORs had no significant prognostic value albeit a trend was observed. In T1-T2 tumours, histological grade (p = 0.05), PNI (p = 0.04) and SPF (p = 0.0076) predicted survival. PMID- 1444229 TI - Cytostatic effect of homo-aza-steroidal esters in vivo and in vitro. Structure activity relationships. AB - The p-[N,N-bis (2-chloroethyl)amino]phenylacetate esters of 3 beta-hydroxy-N methyl-17 alpha-aza-D-homo-5 alpha-androstan-17-one and 3 beta-hydroxy-17 alpha aza-D-homo-5 alpha-androstane have been prepared and their antitumor activity evaluated against L1210 leukemia, P388 leukemia, Ehrlich ascites tumor (EAT) and Lewis Lung Carcinoma (LLC). The results are compared with those of the p-[N,N-bis (2-chloroethyl)amino]phenylacetate of 3 beta-hydroxy-17 alpha-aza-D-homo- 5 alpha androstan-17-one. The above compounds were also tested in vitro against L1210, P 388, EAT and BHX cell cultures. All compounds were found to be active and their structure-activity relationship is discussed. PMID- 1444231 TI - Flow cytometric DNA characteristics of radiation colitis--a preliminary study. AB - The DNA status of 12 rectal biopsies, taken during the investigation of radiation proctitis, was investigated. Of these six were in the acute phase and six in the chronic phase. All of the acute biopsies had diploid DNA, despite bizarre histological epithelial cell appearances. Two of the chronic phase biopsies were to have aneuploid DNA profiles. This finding may be relevant to the increased risk of malignancy in irradiated tissues. PMID- 1444232 TI - Non-toxic sensitization of cancer chemotherapy by combined vitamin C and K3 pretreatment in a mouse tumor resistant to oncovin. AB - The effects of combined vitamin C and K3 i.p. injected 3 hours before i.p. administration of single dose of oncovin, to which the ascites liver tumor in mouse (T.L.T.) was completely resistant, were investigated. This pretreatment sensitized the tumor resistant to oncovin, whereas a separate pretreatment with vitamin C or K3 alone was without any effect. This tumor sensitization to the chemotherapy was completely suppressed by catalase pretreatment, thus indicating that hydrogen peroxide generation with subsequent oxidative stress and its consequences may be involved here. Since this sensitization was without any increased general and organ toxicity, its possible introduction into classical protocols of human cancer treatment would be without any supplementary risk. PMID- 1444233 TI - The relationship between cellular ether glycerophospholipid content and sensitivity of cancer cells to 1-O-octadecyl-2-O-methyl-glycerophosphocholine. AB - Cancer cells are more susceptible to the growth-inhibitory effects of alkyl lysophospholipids than normal cells, but the mechanism of this selectivity is unknown. In this study we have investigated the hypothesis that the sensitivity of cells to alkyl lysophospholipids is related to the cellular ether lipid content. The order of decreasing sensitivity of the cells to the growth inhibitory effect of 1-O-octadecyl-2-O-methyl-glycerophosphocholine (ET-18-OCH3) was MCF 7 > T84 > Malme 3M > A427 > A549, while the order of decreasing ether phospholipid content as a proportion of the total phospholipid was T84 > A427 = A549 = Malme 3M > MCF7. There was also no correlation between ET-18-OCH3 sensitivity and the proportion of ether lipid in the cholineglycerophospholipid or ethanolamineglycerophospholipid classes. Our results clearly indicate that the postulated relationship between ether phospholipid content and ET-18-OCH3 susceptibility may have very limited applicability and is unlikely to be the underlying reason for the selective effects of alkyl lysophospholipids. PMID- 1444234 TI - Inhibition of tumor induction in tobacco by Agrobacterium tumefaciens and nodulation induced by Rhizobium meliloti in the presence of phenothiazines and structurally related compounds. AB - Plasmids of Agrobacterium tumefaciens and Rhizobium meliloti carrying Kanamycin resistance genes were eliminated from 1.4 to 0.2% of the growing bacterial cultures by promethazine and imipramine. As a result of plasmid elimination, the A. tumefaciens plasmidless isolate was not able to induce crown gall tumor on tobacco plants. The plasmidless R. meliloti strain failed to induce nodule formation on alfalfa plants. The efficiency of nodulation was decreased when the bacteria were grown in the presence of the drugs. The antiplasmid effects of the drugs were not prevented by opines, (nopaline and octopine) in Escherichia coli F'lac cells. PMID- 1444235 TI - Relation between the hormonal and epidemiological aspects of esophageal cancer in Japan. AB - Esophageal cancer with endemic distribution of high-risk areas in the world is also known to be more prevalent in the male--and in the aged-populations than in their counterparts. The hormonal characteristics of esophageal cancer patients and the geographical distribution of high and low-risk areas in Japan were comparatively investigated in search of the etiology of this neoplasia. A case control study of 14 urinary steroids indicated that cancer patients of both sexes were associated with an acceleration of cortisone to hydrocortisone conversion within their bodies. Evidence was presented to suggest that the above state of glucocorticoid excess could be related to the production of hyperplasia as well as malignant transformation in the epithelial cells of the esophagus. The 10 highest risk areas and the 7 lowest risk areas were clearly separated by the 2 fault lines of the Japan Islands, a finding to suggest that some microelements of the soil play a role in conditioning the cancer risk. The possible linkage of the observed hormonal characteristics of Japanese patients to both the geochemistry of the soil and the genesis of this neoplasia is discussed in the light of the competitive relationship between the intake of vitamin C and endogenous nitrosation. PMID- 1444236 TI - The response of breast cancer cells to steroid and peptide growth factors. AB - Four breast cancer cell lines covering a wide range of receptor characteristics were examined for their growth responses to oestradiol, insulin, EGF and the anti oestrogen, tamoxifen. Stimulated cellular growth using both the MTT assay and 3H thymidine incorporation into DNA, was measured against controls grown in a steroid reduced environment. The ER positive MCF-7 cell line showed clear growth responses to E2, insulin and EGF. This was also demonstrated, although to a lesser extent in the ZR-75-1 line which expresses lower levels of ER. In combination, these factors gave an additive growth response but the addition of EGF to maximal concentrations of insulin and oestradiol produced no further increase in growth. In contrast to these results, the two ER negative cell lines examined, MCF-7 Adr and MDA-MB-231 showed no growth response to exogenously applied steroids and in the case of MCF-7 Adr high concentrations of EGF were able to inhibit the growth of this cell line. They also showed high rates of growth in a steroid depleted environment which tends to suggest these cells are growing autonomously through autocrine growth factor induction. PMID- 1444237 TI - Age-related decrease in transplantability of human tumours in nu/nu mice. AB - Experiments were designed to assess age-related changes in the transplantability of human tumours xenografted in congenitally athymic (nu/nu) mice. It has been found that the number of progressively growing human tumour xenografts decreased significantly with increasing age of BALB/c nu/nu recipients. These findings, taken together with a previously recognized increase in the frequency of endogenous interleukin 2 (IL-2)-producing cells with age of nu/nu mice, prompted us to investigate whether administration of exogenous IL-2 to young adult nu/nu mice could change the transplantability of human tumours in the mice. Peritumoral administration of exogenous interleukin 2 to 8-week-old nu/nu mice inhibited the growth of the human tumour xenografts. In vitro activation of nu/nu splenocytes with exogenous Il-2 resulted in the generation of killer cells which have been found to be cytolytic when allowed to react with human tumour targets in 51Cr cytotoxicity assay. In addition, it has been found that the percentage of IL-2 activated Thy 1.2+ and ASGM1+ cells substantially increased with increasing age of nu/nu spleen cell donors. These findings are compatible with the hypothesis that the observed age-related decrease in takes of human tumour xenografts might be determined by the increasing level of IL-2 production and subsequent maturation of IL-2-dependent effector cells. PMID- 1444238 TI - Pharmacology, bio-analysis and pharmacokinetics of the vinca alkaloids and semi synthetic derivatives (review). AB - Vinca alkaloids have been used as chemotherapeutic agents now for over three decades. Especially during recent years, the development of a considerable number of semi-synthetic derivatives, showing attractive properties in preclinical or clinical investigations, has been reported. In this paper we shall give a critical review of the investigations presented on this matter. PMID- 1444239 TI - Prevention of myelosuppression does not improve the therapeutic efficacy of chemo immunotherapy. AB - This study was designed to investigate whether the prevention of doxorubicin (DOX) induced myelosuppression could further improve the therapeutic efficacy of chemoimmunotherapy with DOX, interleukin-2 (IL-2) and interferon gamma (IFN gamma). The antitumour activity of systemic IL-2/IFN-gamma immunotherapy in combination with DOX administered either systemically, regionally or on ion exchange microspheres, was assessed in WAG rats bearing hind limb solid colonic adenocarcinoma implants. Whilst the use of microspheres to transport DOX clearly avoided the myelosuppression, systemic and renal toxicity associated with the use of free DOX, it did not provide any therapeutic advantage over chemo immunotherapy with free systemic or regional drug. PMID- 1444240 TI - Detection of K-ras mutations by denaturing gradient gel electrophoresis (DGGE): a study on pancreatic cancer. AB - In pancreatic neoplasias mutations in the first exon (codon 12) of K-ras gene occur at high frequency and seem to have a diagnostic significance. We set up the DGGE conditions to search for these mutations in pancreatic tumor sample DNAs. All samples were directly classified by simply comparing their DGGE patterns with those of control cell lines carrying known K-ras base substitutions. We found a mutation frequency of 73% in pancreatic adenocarcinoma, whereas no mutations were observed in benign lesions. The non-isotopic method we used turned out to be rapid and sensitive. DGGE could therefore be utilized for the detection of K-ras mutations in pancreatic lesions, to evaluate their actual or potential malignancy. In general, DGGE could be useful for K-ras gene screening on pathological tissue samples. PMID- 1444241 TI - Analysis of c-myc oncogene in human esophageal carcinoma: immunohistochemistry, in situ hybridization and northern and Southern blot studies. AB - We have examined the c-myc gene expression and the gene organization in resected human esophageal squamous cell carcinomas, and in the adjacent normal esophageal mucosa from 20 patients undergoing radical surgery. Immunohistochemistry of p62c myc was compared with that of proliferating cell nuclear antigen (PCNA) in order to examine the biologic significance of p62c-myc. Relative c-myc expression detected by Northern blot analysis ranged from 0.41 to 2.8, but the degree of c myc expression did not correlate with other clinicopathological prognostic parameters. In sity hybridization localized the elevated c-myc mRNA expression to tumor cells and basal and parabasal cells of the adjacent normal mucosa. Immunohistochemistry showed altered localization of p62c-myc, i.e., both cytoplasmic and nuclear immunostaining in advanced carcinomas. c-myc immunoreactivity exhibited wider distribution compared with that of PCNA, a cell cycle related antigen, which may indicate induction of cell proliferation by p62c myc. DNA hybridization showed mild amplification in one out of 17 tumors and no evidence of gene rearrangement. There was no distinct correlation between the results of Northern or Southern blot analysis and the results of in situ hybridization or immunohistochemistry. Gene alteration of the c-myc locus, as well as overexpression of the c-myc oncogene, appeared to be limited, and analysis of the c-myc gene yielded limited prognostic value in human esophageal carcinomas. PMID- 1444242 TI - Influence of radiation treatment on serum transferrin and tumor necrosis factor alpha. AB - This study deals with the effect of radiation treatment (RT) on serum transferrin and tumor necrosis factor-alpha (TNF-alpha) in patients with malignant tumors. In 21 patients who received 36-60 Gy in 20 to 30 sessions of RT, serum transferrin and TNF-alpha were determined pre-RT, after 10 to 15 sessions (middle of RT) and after 20 to 30 sessions (end of RT). The values of serum transferrin pre-RT were significantly higher than those in the middle and at the end of RT (p < 0.001). The values of TNF-alpha were increased by RT and were significantly higher at the end of RT as compared to the pre-RT values (p < 0.05). The values of serum transferrin and TNF-alpha show a tendency to negative correlation, either as a whole or separately pre- and under-RT. However, no correlation was statistically significant. PMID- 1444243 TI - [Prenatal screening in utero of urinary abnormalities. Management]. AB - The major benefit of antenatal ultrasonography is to allow early diagnosis of urinary tract malformations before postnatal infection worsens the prognosis. In the majority of cases, there is a unilateral and moderate dilatation requiring a check-up only during the second week of life; treatment subsequently depends on the etiology of the uropathy and the consequences on the kidney. Unilateral severe dilatations and bilateral, but moderate, dilatations must be managed immediately after birth in a pediatric surgical center. In the rare cases of severe bilateral obstructive uropathy, in utero decompression by catheterisation or surgery is now considered to be uselessly invasive, considering that renal dysplasia is already present when the malformation is detected. PMID- 1444244 TI - [Ureteroceles]. AB - Four types of ureteroceles are described: A) ureterocele with single ureter (10%); B) ureterocele with total duplication and intra-vesical development (10%); C) ureterocele with total duplication and extra-vesical development (62%); D) ureterocele with ectopic ureter (3%). Most ureteroceles are now detected by antenatal ultrasonography, allowing early management. The treatment of types A and B is simple depending on the status of the above kidney and ureter: abstention, meatomy, ureterocelectomy with ureteral reimplantation, nephrectomy. In type C, the upper kidney is always destroyed. Two treatments are proposed: upper pole nephrectomy with ureterocelectomy which is a difficult but safe procedure, upper pole nephrectomy with aspiration of the ureterocele which is called the "simplified technique" but requires reoperation in 40% cases. The complicated forms may require either meatotomy for decompression, or diversion by percutaneous nephrostomy. Strangulation of the ureterocele constitutes an emergency. PMID- 1444245 TI - [Enuresis]. AB - The word "enuresis" is the greek word for incontinence. Enuresis has to be considered as a symptom and not as a disease. We have to keep in mind that urine leaking may be due to an anatomical anomaly (epispadias, ectopic ureter, spinal coral lesion, urethral obstacle) in which case treatment of the underlying disease constitutes treatment of enuresis. Nevertheless, enuresis is isolated in 95% of cases. Three groups are defined depending on whether the bladder is normal, hyperactive or retentionnist with bladder-sphincter dyssynergia. We emphasize the frequency of coexistence of these three aspects and the gravity of a wrong diagnosis. The onset or presence of bladder-sphincter dyssynergia is a major concern for the pediatric urologist due to its severity and the difficulties of treatment. PMID- 1444246 TI - [Treatment of idiopathic vesico-ureteral reflux in children]. AB - Vesicoureteral reflux is the principal cause of pyelonephritis in children. Medical treatment is designed to prevent the development of renal parenchymal scars, as these lesions are irreversible and frequently interfere with growth of the kidney. Treatment must therefore be specific and sufficiently prolonged. In infants under the age of 2 years, reflux may resolve in 50% of cases as the ureterovesical junction develops. During this period, treatment consisting of alternating antiseptics should be proposed to prevent the development of pyelonephritis. In all other cases, reflux must be corrected. Two techniques can be proposed at the present time: surgery which gives 98% immediate and permanent good results, using Cohen's technique, and injection of Teflon, which is much less reliable, with risks of distant dissemination, particularly to the brain, and the possibility of developing ureteric stenosis and bladder stones. These problems have led many paediatric urologists to abandon endoscopic treatment. PMID- 1444247 TI - [Current treatment of bladder exstrophy]. AB - The treatment of vesical exstrophy has greatly improved over the last twenty years. The most important progresses are: closing the bladder before the 72nd hour of life; iliac osteotomy allowing fusion of the pubis when closing the bladder; lengthening of the penis by liberation of the corpora cavernosa; entero cystoplasty when the reconstructed bladder is too small. Most surgeons practice the same timing for the different operations. Urinary and genital anomalies can be cured at the same time. In relation to urinary problems, about 80% of cases achieve good continence. An urinary diversion, using "Coffey's" technique, must be performed in the presence of incontinence. Concerning genital problems in boys and girls, reconstructive surgery allows restoration of almost normal genital organs. Intercourse seems to be satisfactory in most cases. There is a high sterility rate in men. PMID- 1444248 TI - [Cystoplasties in children]. AB - Whenever the reservoir function of the bladder is impaired (neuropathic bladder and exstrophy), an enterocystoplasty constitutes a satisfactory solution in children to enlarge the bladder. The various techniques must take into account the degree of alteration of the bladder. The bowel segment must be detubularized, regardless of its origin. The main challenge is to obtain adequate peripheral resistance with easy voiding and filling of the bladder without urine leak, particularly in boys. In girls, the combination of enterocystoplasty and Gobbel Stockel procedure ensures perfect continence between two self-catheterisations. PMID- 1444249 TI - [Renal transplantation in children. Surgical aspects]. AB - The renal transplantation in children has some specificities: urologic anomalies (vesico ureteral reflux, posterior urethral valves) are frequently the cause of the renal failure, and necessitate a thorough surgical preparation before transplantation (nephrectomy, reconstitution of urinary tract). The child must have a sterile, compliant and continent urinary tract on the day of the operation. In small children (< 15 kg), it is often necessary to operate through a transperitoneal incision, especially if the donor is an adult: the anastomoses will then concern the aorta and vena cava. The results are good, even better than in adults, except for very young children (under six years of age). Transplantation with living related donor (LRD) give the best results. Currently, the graft survival is 87% to 90% after three years with LRD, versus 65 to 77% with cadaveric donors. PMID- 1444250 TI - Science and politics: tensions between the head and the heart. PMID- 1444251 TI - Control of cell density and pattern by intercellular signaling in Myxococcus development. AB - Myxococcus xanthus cells feed, move, and develop cooperatively. Genetic, biochemical, and cell mosaic studies demonstrate that cells coordinate their multicellular behavior by transmission of intercellular signals. Starvation for amino acids at sufficiently high density on a solid surface initiates a series of events culminating in the formation of a multicellular structure called a fruiting body filled with dormant, environmentally resistant spores. This review discusses how myxobacteria use extracellular signals to sequentially check the density and arrangement of cells at different stages during development. For at least one early and one late developmental signal, cell density determines the efficiency of intercellular signaling. In turn, proper signaling insures that the appropriate cell density exists, thus controlling the progress of multicellular development in M. xanthus. PMID- 1444252 TI - Genetics of ribosomally synthesized peptide antibiotics. AB - In recent years many peptide antibiotics have been shown to be ribosomally synthesized. Among these are many microcins, produced by diverse strains of gram negative bacteria. While the structures and modes of action of these peptide antibiotics vary widely, many of them share several important features. Their synthesis is often induced by the cessation of growth. In addition, many of them undergo unusual posttranslational modifications to yield the mature molecule, which is often exported from the cell by a dedicated export apparatus. The genes involved in modification and export of the peptide antibiotics are generally found adjacent to the structural gene and are under the same regulation. The results supporting these conclusions are reviewed and discussed in this chapter. PMID- 1444253 TI - Molecular biology of methanogens. AB - Methanogens are a very diverse group of the Archaea (Archaebacteria). Their genomic DNAs range from 26 to 68 mol% G+C; they exhibit all known prokaryotic morphologies and inhabit anaerobic environments as varied as the human gut and deep-sea volcanic vents. They are, nevertheless, unified by their ability to gain energy by reducing CO, CO2, formate, methanol, methylamines, or acetate to methane. Methanogen genes are reviewed and analyzed in terms of their organization, structure, and expression and are compared with their bacterial (eubacterial) and eukaryal (eukaryotic) counterparts. Many methanogens are thermophiles, and some are hyperthermophiles. The influence of these extreme environments on their macromolecular structures is also addressed. Methanogens are oxygen-sensitive, fastidious anaerobes, and therefore their experimental manipulation in research laboratories has been very limited. The majority of the information currently available describing their molecular biology has been gained by gene cloning. With improvements in anaerobic handling procedures, this is beginning to change, and several experimentally tractable regulated systems of gene expression in methanogens are discussed. Anaerobic biodegradation terminating in methane biogenesis is an established, economically very important biotechnology used world-wide both to reduce waste and to generate fuel-grade biogas. The substantial progress made over the past decade, reviewed here, in understanding the molecular biology of methanogens should now provide a data base for considering genetic approaches to improving this process. PMID- 1444254 TI - The biology and genetics of the genus Rhodococcus. AB - The genus Rhodococcus is a unique taxon consisting of microorganisms that exhibit broad metabolic diversity, particularly to hydrophobic compounds such as hydrocarbons, chlorinated phenolics, steroids, lignin, coal, and petroleum. Advances in chemical, numerical, and molecular systematic methods have contributed greatly to the circumspection of the rhodococci, including the development of diagnostic fluoregenic probes for improved biochemical profiling and identification. Bioprocessing systems employing various Rhodococcus strains are operational for industrial and environmental applications. Such applications include production of acrylic acid and acrylamide, steroid conversions, and bioremediation of chlorinated hydrocarbons and phenolics. Progress on the genetic systems of the rhodococci is rather limited, although a number of plasmids, cloning vectors, and DNA transfer systems have been reported recently, such that progress should be rapid. Certain members of the genus Rhodococcus are known pathogens for humans, animals, and plants. Recent trends indicate that rhodococci of animal origin are opportunistic human pathogens, indicating the need for a greatly improved recognition and understanding of the virulence factors associated with the genus Rhodococcus. PMID- 1444255 TI - Biodiversity as a source of innovation in biotechnology. AB - The object of this article is to draw attention to the significance of microbial diversity as a major resource for biotechnological products and processes. The topic is approached from two complementary standpoints. First, an attempt is made to assess the extent of biodiversity, particularly microbial diversity. In this context, the application of the modern techniques of molecular biology is enabling the detection of hitherto completely unknown groups of microbes and, also, is revealing the extent of genetic diversity within microbial taxa. The case is made for the establishment of sound microbial taxonomies both on the basis of satisfying fundamental scientific needs, and for designing effective isolation strategies. The impact of an ecological approach to search and discovery of novel organisms and properties also is emphasized and illustrated. Second, the question of screening a collection of appropriate microorganisms for the desired attributes is considered. The focus here is placed on modern intelligent or targeted screening, and on the power of molecular biology to extend the range of screening options. Discussions of microbial ecology or diversity only rarely touch upon questions of gene pool conservation. The point made here is that loss of biodiversity should be as ominous for microbiologists and biotechnologists as it is to conservationists. The article concludes with thoughts on some means of conserving microbial diversity. PMID- 1444256 TI - The structure and replication of hepatitis delta virus. AB - Hepatitis delta virus exists in nature as a satellite of hepatitis B virus. This review emphasizes studies during the past few years that have clarified much about this satellite relationship. Many unique and intriguing features have been assigned to delta and its replication. In addition, certain unresolved questions are emphasized, and consideration is even given to the application of delta as a vector. PMID- 1444257 TI - The electron-transport proteins of hydroxylating bacterial dioxygenases. AB - The degradation of aromatic compounds by aerobic bacteria frequently begins with the dihydroxylation of the substrate by nonheme iron-containing dioxygenases. These enzymes consist of two or three soluble proteins that interact to form an electron-transport chain that transfers electrons from reduced nucleotides (NADH) via flavin and [2Fe-2S] redox centers to a terminal dioxygenase. The dioxygenases may be classified in terms of the number of constituent components and the nature of the redox centers. Class I consists of two-component enzymes in which the first protein is a reductase containing both a flavin and a [2Fe-2S] redox center and the second component is the oxygenase; Class II consists of three-component enzymes in which the flavin and [2Fe-2S] redox centers of the reductase are on a separate flavoprotein and ferredoxin, respectively; and Class III consists of three-component enzymes in which the reductase contains both a flavin and [2Fe 2S] redox center but also requires a second [2Fe-2S] center on a ferredoxin for electron transfer to the terminal oxygenase. Further subdivision is based on the the type of flavin (FMN or FAD) in the reductase, the coordination of the [2Fe 2S] center in the ferredoxin, and the number of terminal oxygenase subunits. From the deduced amino acid sequence of several dioxygenases the ligands involved in the coordination of the nucleotides, iron-sulfur centers, and mononuclear nonheme iron active site are proposed. On the basis of their spectroscopic properties and unusually high redox potentials, the [2Fe-2S] clusters of the ferredoxins and terminal oxygenases have been assigned to the class of Rieske-type iron-sulfur proteins. The iron atoms in the Rieske iron-sulfur cluster are coordinated to the protein by two histidine nitrogens and two cysteine sulfurs. PMID- 1444258 TI - Exopolysaccharides in plant-bacterial interactions. AB - Rhizobial plant symbionts and bacterial plant pathogens produce exopolysaccharides that often play essential roles in the plant interaction. Many of these exopolysaccharides are acidic heteropolysaccharides that have repeating subunit structures with carbohydrate and noncarbohydrate substituents, while others are homopolysaccharides such as alginate, levan, cellulose, and glucan. While the homopolysaccharides are synthesized by mechanisms that vary with the particular polysaccharide, the heteropolysaccharides as a rule are synthesized by subunit assembly from nucleotide diphosphate-sugar precursors on a membrane-bound lipid carrier followed by polymerization and secretion. Many mutants in exopolysaccharide synthesis have been isolated, and in several cases this has led to the identification of genes that function in particular steps of biosynthesis, as well as in regulation of exopolysaccharide biosynthesis. The genetic regulation of exopolysaccharide synthesis in many plant pathogens is complex, perhaps reflecting the various niches, free living and in planta, in which exopolysaccharides function. In some cases, exopolysaccharide synthesis is regulated coordinately with other virulence factors, and in other cases separately. Regulatory genes that have homology to the two-component sensor and transcriptional effector systems are a common motif. In Rhizobium species, exopolysaccharide synthesis is regulated by transcriptional as well as posttranslational mechanisms. Exopolysaccharides function differently in the root nodule symbiosis versus plant pathogenesis. Specific Rhizobium exopolysaccharide structures promote nodule development and invasion in legumes that form indeterminate nodules. In plant pathogenesis, less specific mechanisms of pathogenesis occur: exopolysaccharides cause wilting by blocking xylem vessels, are partly responsible for water-soaked lesions, and may also aid in invasion, growth, and survival in plant tissues. PMID- 1444259 TI - Double-stranded and single-stranded RNA viruses of Saccharomyces cerevisiae. AB - Yeast RNA viruses include L-A (and its toxin-encoding satellites M1, M2, ...) and L-BC dsRNA viruses and the single-stranded replicons 20S RNA and 23S RNA. L-A has a single-segment 4.6-kb linear genome encoding a major coat protein (gag) and its RNA-dependent RNA polymerase (pol), the latter expressed as a gag-pol fusion protein formed by a -1 ribosomal frameshift. In vitro replication, transcription, and binding systems for L-A have been used to define cis sites necessary for packaging and replication of viral RNA. Cellular functions that promote viral replication include the MAK3-encoded N-acetyltransferase whose modification of the gag N terminus is necessary for L-A virus assembly. The toxins encoded by the M satellite RNAs are processed by enzymes (KEX1 and KEX2, for killer expression) whose study led to discovery of mammalian hormone-processing enzymes. 20S RNA is an apparently naked circular RNA replicon (with a dsRNA form called W) encoding a RNA polymerase-like molecule. Its copy number is induced 10,000-fold in 1% potassium acetate, and it is subject to the same SKI antiviral system that represses L-A, L-BC, and M dsRNA copy number. PMID- 1444260 TI - Genetics of Campylobacter and Helicobacter. AB - This article reviews the current state of genetic analysis of Campylobacter and Helicobacter. Chromosomal genes cloned from Campylobacter and Helicobacter species are listed along with the method used to identify the cloned gene. Campylobacter plasmid genes that have been cloned and expressed in Escherichia coli and that specify resistance to tetracycline, kanamycin, or chloramphenicol are presented. This review also examines our current knowledge of genetic exchange in Campylobacter, including conjugative plasmid transfer, natural transformation, electrotransformation, and bacteriophage transduction. In Helicobacter, natural transformation has been described and both plasmids and bacteriophages have been observed. Plasmid cloning vectors have been constructed for Campylobacter. Available vectors are discussed and restriction maps of some useful vectors that we have constructed are included. The genome sizes of C. jejuni and C. coli are approximately 1.7 megabases (Mb), whereas the genome size of H. pylori ranges from 1.60 to 1.73 Mb. The positions of various genes on the C. jejuni and C. coli genome maps have been determined using both homologous and heterologous DNA probes. Genomic maps of these organisms are presented. PMID- 1444261 TI - Autoregulatory factors and communication in actinomycetes. AB - The ability to produce a wide variety of secondary metabolites and a mycelial form of growth that develops into spores are two biological aspects characteristic of the gram-positive bacterial genus Streptomyces. Secondary metabolism and cell differentiation are controlled by diffusible low-molecular weight chemical substances called autoregulators. A-factor, the representative of the autoregulators, triggers streptomycin production and aerial-mycelium formation in Streptomyces griseus. A-factor exerts its regulatory function with the aid of a receptor protein that itself acts as a repressor-type regulator. The A-factor signal via the A-factor-receptor protein is transferred to downstream genes, such as streptomycin-production genes and sporulation genes, through multiple regulatory genes in a complex regulatory cascade. Thus, A-factor can be termed a "microbial hormone." This review deals with the A-factor-regulatory cascade as a model system for other autoregulators. The biosynthesis of A-factor, the structures and characteristics of other autoregulators, and the importance of these autoregulators in the ecosystem are also included. PMID- 1444262 TI - Genetics of competition for nodulation of legumes. AB - An economically important problem in microbial ecology concerns the efficacy of rhizobial inoculants for the formation of nitrogen-fixing root nodules on legume crop plants such as soybean, alfalfa, and clover. Some strains of rhizobia can increase symbiotic nitrogen fixation under controlled conditions. However, attempts to improve nitrogen fixation under agricultural conditions with such strains often fail, usually as a result of the presence of indigenous rhizobia limiting nodulation by the inoculum strains. This problem is referred to as the Rhizobium competition problem, and molecular genetics is being used to address the problem from two perspectives. First, the host specificity of rhizobia is being characterized with the long term goal of developing strains that can nodulate a very strain-specific host-legume genotype. Second, the genetic basis of competitiveness in several strains is being examined. Genetic determinants of nodulation competitiveness have been isolated and mechanisms for their stable integration into the genome of superior nitrogen-fixing strains have been developed. Several phenotypes have been identified as playing an important role in nodulation competitiveness including antibiosis, motility, speed of nodulation, cell-surface characteristics, and nodulation efficiency. Several solutions to this problem are likely to result from these strategies and will be useful for certain legumes in specific locations. PMID- 1444263 TI - Positive regulation in the gram-positive bacterium: Bacillus subtilis. AB - Temporally and environmentally regulated gene expression in prokaryotes occurs primarily at the level of transcription initiation. Two main modes of regulation have been described, including either the binding of a repressor that blocks transcription or the interaction of a positive regulator with the transcription complex, leading to transcription initiation. Several classes can be distinguished among positive regulators according to their mechanisms of action. This review describes the different types of positive regulators identified in Bacillus subtilis, a gram-positive bacterium. These include accessory regulatory polypeptides, classical positive regulators that bind to target sites located just upstream from the promoter, ambiactive regulators that can act both positively and negatively, antiterminators, two-component signal transduction systems, and positive regulators associated with specific secondary sigma factors. PMID- 1444264 TI - Penicillin and cephalosporin biosynthetic genes: structure, organization, regulation, and evolution. AB - Penicillins and cephalosporins are produced by a wide variety of microorganisms, including some filamentous fungi, many gram-positive streptomycetes, and a few gram-negative unicellular bacteria. All produce these beta-lactam antibiotics by essentially the same biosynthetic pathway. Recently, most of the penicillin and cephalosporin biosynthetic genes have been cloned, sequenced, and expressed. The biosynthetic genes code for enzymes that possess multifunctional peptide synthetase, cyclase, epimerase, expandase, hydroxylase, lysine aminotransferase, and acetyltransferase activities and are organized in chromosomal gene clusters and coordinately expressed. DNA hybridization screens of streptomycetes demonstrate that beta-lactam biosynthetic genes may be more widespread in nature than is indicated by conventional antibiotic screens. They offer the possibility of expanding the search for organisms with potential to make new beta-lactam antibiotics. Attempts to improve current yields of beta-lactams in production strains by introducing into them additional copies of biosynthetic genes have been partially successful. Comparative sequence analysis of bacterial and fungal beta-lactam biosynthetic genes show they share very high sequence identity. A model that explains the similarity of biosynthetic genes from an evolutionary standpoint assumes horizontal gene-transfer between the two groups of organisms. Indirect evidence suggests the transfer occurred from the bacteria to the fungi. PMID- 1444265 TI - Signaling and host range variation in nodulation. AB - Rhizobium, Bradyrhizobium, and Azorhizobium strains, collectively referred to as rhizobia, elicit on their leguminous hosts, in a specific manner, the formation of nodules in which they fix nitrogen. Rhizobial nod genes, which determine host specificity, infection, and nodulation, are involved in the exchange of low molecular weight signal molecules between the plant and the bacteria as follows. Transcription of the nod operons is under the control of NodD regulatory proteins, which are specifically activated by plant flavonoid signals. The common and species-specific structural nod genes are involved in turn in the synthesis of specific lipo-oligosaccharides that signal back to the plant to elicit root hair deformations, cortical-cell divisions, and nodule-meristem formation. PMID- 1444266 TI - The natural history and pathogenesis of HIV infection. AB - Infection with human immunodeficiency virus (HIV) results in progressive deterioration of the cell-mediated immune system characterized by T-helper-cell dysfunction and loss in the face of signs of generalized immune-system activation. The final stage of HIV disease, AIDS, has a myriad of opportunistic infections and malignancies as its hallmarks. The causal relationship between HIV and this complex disease pattern is clear but the mechanisms by which it occurs are not well understood. There are a number of new developments in our understanding of the natural history of HIV infection from a laboratory standpoint. Our review of this information raises further questions as to the validity of the conventional "cytopathic" model and all its direct descendants. In response to these conflicts, we have developed and present an alternative hypothesis in which AIDS pathogenesis, in all its manifestations, is seen as the outcome of one central process, excess immune activation generated by the interaction of virus with the CD4 receptor. The implications of this hypothesis on therapy of HIV infections are discussed. PMID- 1444267 TI - Functional and evolutionary relationships among diverse oxygenases. AB - Oxygenases that incorporate one or two atoms of dioxygen into substrates are found in many metabolic pathways. In this article, representative oxygenases, principally those found in bacterial pathways for the degradation of hydrocarbons, are reviewed. Monooxygenases, discussed in this chapter, incorporate one hydroxyl group into substrates. In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of NAD(P)H. Dioxygenases catalyze the incorporation of two atoms of dioxygen into substrates. Two types of dioxygenases, aromatic-ring dioxygenases and aromatic-ring-cleavage dioxygenases, are discussed. The aromatic ring dioxygenases incorporate two hydroxyl groups into aromatic substrates, and cis-diols are formed. This reaction also requires NAD(P)H as an electron donor. Aromatic-ring-cleavage dioxygenases incorporate two atoms of dioxygen into aromatic substrates, and the aromatic ring is cleaved. This reaction does not require an external reductant. All the oxygenases possess a cofactor, a transition metal, flavin or pteridine, that interacts with dioxygen. The concerted reactions between dioxygen and carbon in organic compounds are spin forbidden. The cofactor is used to overcome this restriction. For the oxygenases that require the NAD(P)H cofactor, the enzyme reaction is separated into two steps, the oxidation of NAD(P)H to generate two reducing equivalents, and the hydroxylation of substrates. Flavoprotein hydroxylases that catalyze the monohydroxylation of the aromatic ring carry out these two reactions on a single polypeptide chain. In other oxygenases, the NAD(P)H oxidation and a hydroxylation reaction are catalyzed by two separate polypeptides that are linked by a short electron-transport chain. Two reducing equivalents generated by the oxidation of NAD(P)H are transferred through the electron-transport chain to the cofactor on a hydroxylase component that they reduce. Dioxygen couples with the reduced cofactor and subsequently hydroxylates substrates. The electron-transport chains associated with oxygenases contain at least two redox centers. The first redox center is usually a flavin, while the second is an iron-sulfur cluster. The electron transport is initiated by a single two-electron transfer from NAD(P)H to a flavin, followed by two single-electron transfers from the flavin to an iron sulfur cluster. The primary sequences of many oxygenases have been determined, and according to their sequence similarities, the oxygenases can be grouped into several protein families. Among proteins of the same family, the sequences in regions involved in cofactor binding are strongly conserved. Local sequence similarities are also observed among oxygenases from different families, primarily in regions involved in cofactor binding. PMID- 1444268 TI - Arrest of bacterial DNA replication. AB - The chromosomes of both gram-positive and gram-negative bacteria contain sites that arrest the progression of DNA replication forks. These replication-arrest sites limit the end of the replication cycle to a particular region of the chromosome, called the terminus region. Replication arrest is mediated by protein DNA complexes that show polarity of function: they arrest DNA replication from one direction only. This paper reviews our current knowledge of the replication arrest complexes of Bacillus subtilis and Escherichia coli and examines possibilities for the function and mechanism of action of these complexes within the bacterial cell. PMID- 1444269 TI - The lipophosphoglycan of Leishmania parasites. AB - Protozoan parasites of the genus Leishmania have the remarkable ability to avoid destruction in the hostile environments they encounter throughout their life cycle. The molecular details of how these pathogens persevere with impunity under harsh conditions are beginning to be understood. The fact that Leishmania parasites have adapted to not only survive, but to proliferate probably is due to the protection conferred by specialized molecules on the parasite's cell surface. One such macromolecule is a novel glycoconjugate called lipophosphoglycan. This heterogeneous, lipid-containing polysaccharide is the major surface molecule of the parasite and has been implicated in a surprisingly large number of functions that may contribute the the parasite's pathogenesis. This review emphasizes the structural aspects of lipophosphoglycan and its possible functions and biosynthesis. PMID- 1444270 TI - Human immunodeficiency virus and the central nervous system. AB - Neurological disease frequently complicates HIV-1 infection. In addition to opportunistic infections, a syndrome of combined cognitive and motor impairment, referred to as the AIDS dementia complex, has been recognized. While presumed to relate to HIV-1 itself, the pathogenesis of this syndrome remains uncertain. Because of the limited extent of productive brain HIV-1 infection in many cases, and because such infection involves macrophages and microglia rather than cells of neuroectodermal origin, current speculation centers on indirect mechanisms of brain injury including virus- or cell-coded neurotoxins. We review clinical and laboratory studies and also describe models of the interaction of HIV-1 and immune responses that might account for brain injury. PMID- 1444271 TI - Metabolism and functions of trypanothione in the Kinetoplastida. AB - Trypanosomatids differ from all other organisms in their ability to conjugate the sulfur-containing tripeptide, glutathione, and the polyamine, spermidine, to form trypanothione [N1,N8-bis(glutathionyl)spermidine]. Together with the NADPH dependent flavoprotein, trypanothione reductase, the dithiol form of trypanothione provides an intracellular reducing environment in these parasites, substituting for glutathione and glutathione reductase found in the mammalian host. Trypanothione and its related enzymes are involved in defense against damage by oxidants, certain heavy metals, and possibly xenobiotics. Trypanothione and its metabolic precursor, glutathionylspermidine, are also implicated in the modulation of spermidine levels during growth. Several existing trypanocidal drugs interact with the trypanothione system, suggesting that trypanothione metabolism may be a good target for the development of new drugs. The purification and properties of three key enzymes (glutathionylspermidine synthetase, trypanothione synthetase, and trypanothione reductase) are discussed, and the catalytic mechanism, substrate-specificity, and the three-dimensional structure of trypanothione reductase are compared to that of glutathione reductase. PMID- 1444272 TI - Replication cycle of Bacillus subtilis hydroxymethyluracil-containing phages. AB - The present review focuses on phage 2C, a member of a family of virulent phages that multiply in Bacillus subtilis. The best known members of this group are SPO1, phi e, H1, 2C, SP8, and SP82, the genomes of which are made of double stranded DNA of about 150 kilobase pairs (kbp). The two DNA strands have different buoyant densities. Moreover, thymine (T) is completely replaced by hydroxymethyluracil (hmUra). Comparison of the phage DNAs has shown that both base substitutions and deletions have contributed to the evolution of their genomes. In addition, all of the hmUra-phage genomes contain colinear redundant ends, amounting to 10% of total bases. Two lines of evidence suggest that the redundant ends of 2C DNA, in spite of extensive homology, contain unique sequences. Further studies focused on DNA replication during the lytic cycle. The semiconservative replication of the infecting viral genome is followed by extensive recombination. At the level of replication forks, viral DNA synthesis is discontinuous on both strands during the whole cycle. Deoxythymidinetriphosphate, required for viral DNA synthesis in permeabilized infected bacteria, was incorporated in small amounts into phage DNA. The putative primary origin of replication has been cloned and localized on the viral genome. Some viral promoters have been successfully cloned in Escherichia coli. These sequences, however, did not promote transcription in B. subtilis. The abnormal base might be required for promoter activity in the natural host. PMID- 1444273 TI - The anthropological evidence for change through Romanisation of the Poundbury population. AB - Poundbury Camp cemetery was in use for about 500 Years and was the burial ground for an Iron Age Durotrigian group, a rural Roman settlement and an urban Romano British community. Low variance of metrical characters and persistence of familial traits in the three groups suggest a continuity of the population and in situ growth. However evidence for an anthropological response to the cultural romanisation of the population has been found in a number of skeletal traits including squatting which was most often adopted by Durotrigian females. Dietary changes are indicted by variation in concentrations of trace elements, including lead, in the bones. PMID- 1444274 TI - Ancient skeletal remains of the Canary Islands: bone histology and chemical analysis. AB - Prehispanic burials from the Canary Islands are often well preserved. Many of the bodies are mummified, most of them were not interred, but deposited in caves. Bone histological and trace element analysis of 117 skeletons of the prehispanic period of the Canary Islands was performed. In some of the islands we have found a high prevalence of osteoporosis, whereas in others, histomorphometrically assessed trabecular bone mass (TBM) (in undecalcified iliac crest specimens) was in the normal range. Bone trace elements analysis have shown high bone S(r), Mg and Mn, and low Fe, Zn and Cu in those skeletons with a more reduced TBM. These facts speak for a relative protein-calorie malnutrition and a consumption of a mainly vegetarian diet. This is especially marked in the skeletons from Gran Canaria. PMID- 1444275 TI - Anthropometrical study of the Asmat (Irian Jaya). AB - An anthropometric study in the Asmat population, a coastal group of Papua living in the south-western part of Irian Jaya (Indonesian New Guinea) covered 318 subjects of both sexes, belonging to four different villages (Basim, Senggo, Ewer and Piramanak) of the Asmat region. The dimensions and derived indices, describing body, head and face morphology as well as body composition show the Asmat to be slender and muscular, with shoulders, chest and pelvis of medium dimensions and with long legs in relation to the trunk. They are dolichocephalic with narrow faces and rather large noses. Comparisons of the four Asmat groups indicate the importance of geographic position on size of the subjects and the similarities detected between the groups by discriminant and principal component analysis. PMID- 1444276 TI - [The color and structure of the human iris. 2. Studies of 200 twins]. AB - Subject of the present report is an investigation of the heredity of 30 iris characteristics. The material basis of this sample of twins (100 monozygotic and 100 dizygotic pairs), the largest ever taken as a basis for the purpose of iris research, consists of standardized colour photographs of the examined persons' irises and iris-microscopic observations. The pairs of twins are compared to 100 non-related casual pairs in order to render a better estimation of the degree of heredity of the features possible. On every occasion several classes were constituted for the concordance verification. These classes result from the number of the classes of the forms of markedness and present different levels of similarity. The different distribution of the twin pairs and the control pairs on the concordance classes are always examined for their statistical significance, and for each group of pairs a concordance value is computed. The intervals between the concordance values of the monozygotic and dizygotic pairs and the control pairs indicate the degree of heredity of the investigated feature. Taking all the compiled factors and conditions into consideration, an evaluation of the features as heredity features is made. Though a hereditary component can be observed for all iris characteristics, only about a third could be called heredity features. Quantity of pigment and the hitherto undescribed limiting layer folds were evaluated as "very good", whereas pigment colour in the fine analysis, quality of the anterior stroma leaf, frequency of iris crypts and iris frill position were judged as "good". Tone of blue, markedness of Woelfflin nodules, quantity and markedness of contractional rings could be evaluated as "moderately good" as to their heredity. On the basis of the prior concordance investigations for each of the 300 pairs, a "similarity index" and a "concordance index" were computed in order to arrive at evidence as to the degree of similarity of the single pairs; i.e. in order to detect the limits of the similarity between non-identical twins and the dissimilarity between identical twins. This concluding investigations lead to the question of the possibility of a diagnosis of genetic identicalness solely on the basis of the comparison of irises. PMID- 1444277 TI - Discipline of nursing. PMID- 1444278 TI - The real and the ideal. PMID- 1444279 TI - Fighting back: promoting emancipatory nursing actions. AB - Poverty, education, and social problems are inextricably linked to health concerns and cannot be addressed in isolation from each other. Nurses are being challenged to care for clients who are socially, politically, and economically disadvantaged. The model of emancipatory nursing actions is derived from the work of Freire, Habermas, and Katz and presented as a practice model in guiding nurses to begin choosing actions that seek to help people fight back from the depths of their despair, rather than helping people cope and adapt to their oppression. Emancipatory interventions are provided to help nurses launch a new direction toward freeing their clients, rather than herding them through an uncaring and disjointed health and social service system. PMID- 1444280 TI - Conceptual and methodological issues in nurse case management research. AB - Conceptual and methodological issues facing researchers who are studying the process and outcomes of nurse case management are identified. The evolution of a research program designed to understand and evaluate one model of nurse case management is described as an example of responding to these issues. The development of a body of knowledge around nurse case management is essential to assure the expansion of this role and to justify reimbursement through current and evolving insurance mechanisms. PMID- 1444281 TI - Nursing care partnerships at the Denver Nursing Project in Human Caring: an application and extension of caring theory in practice. AB - Jean Watson's theory of nursing as the art and science of human caring provides the framework for practice at the Denver Nursing Project in Human Caring, a nurse managed center for people living with HIV/AIDS. The purpose of this article is to describe the development, implementation, and evaluation of a new model of nursing practice at the Caring Center, called nursing care partnerships. Client and nurse narrative accounts are presented as a means of grounding the reader in the care partners' relationships that are formed during the journey of HIV/AIDS. PMID- 1444282 TI - Components of nurse innovation: a model from acute care hospitals. AB - Components that promote nurse innovation in acute care hospitals are explicated in the Acute Care Nursing Innovation Model. Grounded in nursing care delivery systems and excellent management-organizations perspectives, nurse executives and 30 nurse "intrapreneurs" from 10 innovative hospitals spanning the United States shared their experiences and insights through semistructured, tape-recorded telephone interviews. Guided by interpretive interactionist strategies, the essential components, characteristics, and interrelationships are conceptualized and described so that others may be successful in their innovative endeavors. Successful innovation is dependent on the fit between and among the components; the better the fit, the more likely the innovation will succeed. PMID- 1444283 TI - Parse's theory as a model for practice: the cutting edge. AB - If nursing practice is the performing art of the science of nursing, then practice is guided by nursing theory and cannot be considered separately from it. Nursing theory based practice is the cutting edge of the discipline. Practice methods reflect the beliefs and values of the theories from which they evolve. Nurses' values and beliefs about human beings and health are incarnated in the way they practice. This article presents Parse's theory of human becoming as a model for practice; explicates the beliefs, values, and ethic of the practice method; analyzes the logical coherence of theory and method; illustrates the pragmatics of the method, and gives evidence of its soundness. The theory research-practice triad developed by Parse articulates a paradigmatic view of the discipline as a whole with a view of the human being as a living unity freely choosing personal meanings in life situations. Parse's practice methodology provides nurses with a way of practicing with a focus on the quality of life as it is humanly lived. It is presented here as the practice component of an emergent theory-research-practice tradition on the cutting edge of nursing science. PMID- 1444284 TI - Family nursing practice paradigm perspectives and diagnostic approaches. AB - Family nursing practice reflects different belief systems about the nature of the family and family health. Competing belief systems (paradigms) are examined as they relate to the concepts of concern to family nursing. Using a family case study, divergent diagnostic approaches emerging from the paradigms are described and demonstrated. Implications are delineated for the further development of family nursing practice. PMID- 1444285 TI - Nursing practice model for maternal role sufficiency. AB - In 1975 Meleis set forth a conceptual framework for nursing practice centered on the concepts of role insufficiency and role supplementation. Later, Millor introduced a parental role sufficiency model for nursing research in child abuse and neglect. Based on the works of Meleis and Millor, a nursing practice model is proposed that focuses on maternal role sufficiency. It includes assessment of prenatal characteristics, measurement of developmental and health-illness outcomes, and preventive role supplementation intervention. PMID- 1444287 TI - Pharmacokinetic-interaction study of didanosine and ranitidine in patients seropositive for human immunodeficiency virus. AB - The potential pharmacokinetic interactions between didanosine, an acid-labile antiretroviral agent, and ranitidine, an H2-receptor antagonist, were evaluated by a crossover study of 12 male patients seropositive for the human immunodeficiency virus. Single oral doses of 375 mg of didanosine, formulated as a citrate-phosphate-buffered sachet, or of 150 mg of ranitidine were administered alone or in combination (ranitidine was given 2 h prior to didanosine). Serial blood samples and total urinary output were collected after each treatment and analyzed for didanosine and/or ranitidine by validated high-performance liquid chromatography-UV assay methods. Pharmacokinetic parameters were calculated by noncompartmental methods. There were significant increases in mean area under the curve from time zero to infinity and mean urinary recovery for didanosine given in combination with ranitidine compared with those for didanosine alone. There were no significant differences between didanosine coadministered with ranitidine and didanosine alone in the respective mean peak concentrations in plasma, times to peak, elimination half-lives, or renal clearances. The mean area under the curve for ranitidine given with didanosine was significantly less than that for ranitidine given alone. There were no significant differences between the mean peak concentrations in plasma, times to peak, elimination half-lives, renal clearances, or urinary recovery values for ranitidine coadministered with didanosine and values for ranitidine given alone. These data demonstrate that administration of didanosine 2 h after ranitidine will result in a minor increase in the bioavailability of didanosine. A modification in the dose of didanosine or ranitidine is not necessary if the dose of ranitidine precedes that of didanosine by 2 h. PMID- 1444286 TI - Pharmacokinetic and pharmacodynamic requirements for antibiotic therapy of experimental endocarditis. PMID- 1444288 TI - CP-72,588, a semisynthetic analog of the polyether ionophore UK-58,582 with increased anticoccidial potency. AB - We have employed semisynthesis to enhance the anticoccidial potency of a polyether ionophore. CP-72,588 is the alpha-methyl analog of the fermentation derived polyether ionophore UK-58,852. The parent ionophore required a dose of 15 ppm to achieve anticoccidial efficacy in chickens equivalent to that of salinomycin at 60 ppm. CP-72,588 demonstrated substantially improved potency, with efficacy at 5 to 7.5 ppm. The intrinsic antimicrobial potencies of the two ionophores are similar; however, CP-72,588 was found in chicken tissues at higher levels than those of the parent ionophore when each was administered at the same dose (8 ppm). The enhanced potency of CP-72,588 may be partially due to enhanced uptake into tissues. PMID- 1444289 TI - Comparative study of pharmacokinetics and serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin. AB - We compared the pharmacokinetics and the serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin. Fifteen healthy volunteers received 1 g of cefpirome, ceftazidime, and ceftriaxone intravenously, 500 mg of imipenem-cilastatin intravenously, and 500 mg of ciprofloxacin orally. High-performance liquid chromatographic assays were used to quantitate unchanged antibiotic in plasma and urine. Serum bactericidal activities were determined against six clinical isolates each of Staphylococcus aureus, Enterobacter cloacae, and Pseudomonas aeruginosa by using a modified microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196 204, 1977). Overall, cefpirome exhibited pharmacokinetics similar to those of ceftazidime: half-life (t1/2), 1.95 h; concentration at 1 h (C1h), 47 to 49 micrograms/ml for both antibiotics. Ceftriaxone displayed the longest t1/2 (7.65 h) and the highest C1h (137.8 micrograms/ml), while we observed the shortest t1/2 (1.05 h) and the lowest C1h (19.85 micrograms/ml) with imipenem. At 1 h, cefpirome and, even more so, imipenem showed significantly better serum bactericidal activities against S. aureus (1:273 and 1:80) than did the other antibiotics (P less than 0.0005; analysis of variance with randomized block design and Bonferroni correction). Against E. cloacae, we observed the highest serum bactericidal titers at 1 h with cefpirome, and this superiority vis-a-vis the other antibiotics tested was maintained for up to 8 h after dosing. Ceftazidime remained the most active agent tested against P. aeruginosa (serum bactericidal activity titers, 1:43 at 1 h) up to 8 h. In summary, the study showed that cefpirome and imipenem provide more potent serum bactericidal activities than do broad-spectrum cephalosporins against S. aureus; thus, both of these antibiotics should be adequate against serious S. aureus infections. In addition, cefpirome appears to be a promising alternative for treatment of infections caused by E. cloacae and P. aeruginosa. PMID- 1444290 TI - Effects of sub-MICs of antibiotics on cell surface characteristics and virulence of Pasteurella multocida. AB - The effects of sub-MICs of certain antibiotics, namely, penicillin G, tetracycline, and trimethoprim-sulfamethoxazole, on the cell surface characteristics and the virulences of two toxigenic isolates of Pasteurella multocida representing capsular types A and D were evaluated. Expression of proteins, in particular, outer membrane proteins and iron-regulated proteins, was not affected by exposure of bacterial cells to low concentrations of antibiotics. However, exposition of surface antigens was modified by sub-MICs of the antibiotics tested. The lipopolysaccharide profile of one isolate (capsular type D) was altered by penicillin G. Sub-MICs of penicillin G and tetracycline diminished the virulence of the capsular type A isolate and adherence to porcine tracheal rings of the capsular type D isolate. Production of dermonecrotic toxin was not affected by sub-MICs of the antibiotics tested. Our results indicate that growth of P. multocida in the presence of low concentrations of antibiotics seems to have, depending on the isolate, profound effects on cell surface characteristics, with concomitant effects on adherence or virulence. Our results also indicate that production of dermonecrotic toxin, an important virulence factor of P. multocida isolates associated with porcine atrophic rhinitis, was not affected by sub-MICs of the antibiotics studied. PMID- 1444291 TI - Penetration of cefpodoxime proxetil in lung parenchyma and epithelial lining fluid of noninfected patients. AB - The pulmonary disposition of cefpodoxime was studied in 12 patients with pulmonary opacities after a single oral dose of 260 mg of cefpodoxime-proxetil, which is equivalent to 200 mg of cefpodoxime. Blood and lung tissue samples were collected during surgery, and bronchoalveolar lavage was carried out 3 h (group A) or 6 h (group B) after drug administration. Urea was used as an endogenous marker for measurement of the volume of epithelial lining fluid (ELF). Concentrations were measured by using a microbiological assay. The mean concentrations of cefpodoxime in plasma, ELF, and lung tissue were, respectively, 1.85 +/- 0.82 mg/liter, 0.22 +/- 0.13 mg/liter, and 0.89 +/- 0.80 mg/kg of body weight in group A and 1.40 +/- 1.25 mg/liter, 0.12 +/- 0.14 mg/liter, and 0.84 +/ 0.61 mg/kg in group B. Concentrations in lung parenchyma 6 h after dosing were at least equal to or above the MICs for 90% of the strains of most organisms commonly found in respiratory tract infections, whereas data for ELF suggest levels of drug insufficient to inhibit bacteria. PMID- 1444292 TI - Microbiological efficacy and pharmacokinetics of prophylactic antibiotics in liver transplant patients. AB - The pharmacokinetics of perioperative systemic antibiotics and the microbiological effectiveness of oral nonabsorbable antibiotics started immediately prior to surgery were studied in 18 adult patients undergoing liver transplantation. All patients received cefotaxime, 2 g intravenously, at 6-h intervals during surgery and then at 8-h intervals thereafter for 48 h; eight patients also received ampicillin at the same dose and schedule. This regimen produced levels of antibiotics in blood that appeared appropriate for prophylaxis. The first dose peak (68 +/- 18 micrograms/ml) and trough (6.9 +/- 4.7 micrograms/ml) levels of cefotaxime in serum and the first dose peak (73 +/- 22 micrograms/ml) and trough (4.1 +/- 2.3 micrograms/ml) levels of ampicillin in serum, which were assayed by high-performance liquid chromatography, were similar to levels reported in normal volunteers, despite mean intraoperative blood loss of 3.3 liters and fluid replacement of 21 liters. On postoperative days 1 and 2, the levels of cefotaxime and ampicillin were maintained at or above 0.9 and 1.3 micrograms/ml, respectively, with little accumulation. By random assignment, 8 patients received systemic antibiotics alone and 10 patients received systemic antibiotics plus a 3-week regimen of oral nonabsorbable antibiotics (gentamicin, polymyxin E, and nystatin) beginning when a donor liver was procured. Pre- and postoperative cultures of rectum, throat, and gastric aspirate samples showed persistence of aerobic gram-negative bacilli for the first 2 postoperative weeks in about half of the patients in each group. Failure of the regimen of oral nonabsorbable antibiotics to supplement cefotaxime in eradicating aerobic gram negative bacilli from stools probably results from impaired peristalsis during and after surgery and warrants earlier initiation of the regimen. PMID- 1444293 TI - Endotoxin concentration in neutropenic patients with suspected gram-negative sepsis: correlation with clinical outcome and determination of anti-endotoxin core antibodies during therapy with polyclonal immunoglobulin M-enriched immunoglobulins. AB - We carried out a study in patients with severe neutropenia from hematologic malignancy and suspected gram-negative sepsis to evaluate the clinical significance of endotoxin concentrations in plasma before and during a therapeutic intervention with a human polyclonal immunoglobulin M (IgM)-enriched immunoglobulin preparation (Pentaglobin; Biotest, Dreieich, Germany). Twenty-one patients with acute leukemia or non-Hodgkin's lymphoma entered the study upon the development of clinical signs of gram-negative sepsis and received the IgM enriched immunoglobulin preparation every 6 h for 3 days (total dose, 1.3 liter with 7.8 g of IgM, 7.8 g of IgA, and 49.4 g of IgG), in addition to standardized antibiotic treatment. Concentrations of endotoxin and IgM and IgG antibodies against lipid A and Re lipopolysaccharide (LPS) in plasma were determined by a modified chromogenic Limulus amebocyte lysate test and semiquantitative enzyme linked immunosorbent assay, respectively, before each immunoglobulin infusion and during the following 25 days. Seventeen patients were endotoxin positive; in five of these patients, gram-negative infection was confirmed by microbiologic findings. Prior to therapy, endotoxemia correlated significantly with the occurrence of fever, and a quantitative correlation between the endotoxin concentration and body temperature was found during the individual course of infection in 8 of the 17 patients. Overall mortality from endotoxin-positive sepsis was 41% (7 of 17) and 64% (7 of 11) in patients with symptoms of septic shock. Nonsurvivors had significantly higher maximum concentration of endotoxin in plasma compared with those of survivors at the first study day (median of 126 versus 34 pg/ml; P < 0.05) and during the whole septic episode (median of 126 versus 61 pg/ml; P < 0.05). In survivors, immunoglobulin therapy resulted in a significant decrease in endotoxin levels in plasma within the initial 18-h treatment period, from a pretreatment median value of 28 pg/ml to a value of 8 pg/ml (P< 0.05). In the seven patients who died from uncontrollable infection, no effect of therapy on endotoxin levels in plasma was observed. IgM and IgG antibodies against lipid A and Re LPS increased significantly under immunoglobulin treatment, with significant correlations between antibodies against lipid A and Re LPS. These data strongly suggest a prognostic significance of the endotoxin levels in plasma and a potential effect of treatment with a polyclonal IgM-enriched immunoglobulin preparation. Further studies are needed to substantiate these findings and to assess the impact on the clinical course by way of a prospective placebo-controlled clinical trial. PMID- 1444294 TI - Effect of beta-lactams on peptidoglycan metabolism of Haemophilus influenzae grown in animals. AB - We have examined bacterial determinants that influence beta-lactam activity in Haemophilus influenzae cells cultivated in a system that reproduces in vivo growth conditions. Bacteria grown in diffusion chambers were recovered from the peritoneal cavities of rats, and their cell properties were compared with those of bacteria grown in broth cultures by various tests performed in vitro. The rate of peptidoglycan synthesis was measured as the incorporation of [14C]alanine into cell wall material in the presence of chloramphenicol. The total incorporation of [14C]alanine into peptidoglycan was markedly increased in cells grown in rats prior to the assay but was efficiently reduced by the beta-lactams. The extent of cross-linking was lower in the peptidoglycan of in vivo-grown bacteria, as estimated by sodium dodecyl sulfate- to trichloroacetic acid-insoluble radioactive cell wall material ratios. A whole-cell labeling assay with 125I penicillin was used to characterize the penicillin-binding proteins (PBPs). Four PBPs showed a striking reduction in the binding of the labeled penicillin in cells grown in rats. Such changes resembled the PBP alterations seen in beta lactamase-negative clinical strains that were resistant to the beta-lactams. Although ampicillin and moxalactam showed delayed inhibitory activities in vitro for cells collected from rats, cells recovered from beta-lactam-treated rats showed evidence of antibiotic effectiveness (binding of the beta-lactams to PBPs in vivo and altered morphology), and the killing of cells exposed to antibiotics in broth or in peritoneal fluid was equally good. Finally, the frequencies of spontaneous resistance or tolerance to ampicillin or moxalactam were estimated, and there was no significant difference for in vitro- or in vivo-grown cells. These data demonstrated that the cultivation of H. influenzae in animals created changes in PBPs and the overall peptidoglycan metabolism. Such alterations did not impair the bactericidal activities of the beta-lactams, although they resulted in delayed bacterial inhibition, a phenomenon that may have important consequences in antibiotherapy. PMID- 1444295 TI - Central nervous system targeting of 2',3'-dideoxyinosine via adenosine deaminase activated 6-halo-dideoxypurine prodrugs. AB - AIDS dementia complex is a neurologic disorder, characterized by increasingly severe cognitive, behavioral, and motor impairment, which is associated with human immunodeficiency virus (HIV) infection in the central nervous system (CNS). Many of the dideoxynucleosides effective systemically in the treatment of HIV infections, such as 2',3'-dideoxyinosine (ddI), exhibit limited penetration into the CNS and limited or variable effectiveness in reversing the symptoms of AIDS dementia. Thus, approaches for increasing the CNS uptake of ddI and other dideoxynucleosides are needed. The CNS uptake of a series of 6-halo-2',3' dideoxypurine ribofuranosides (6-halo-ddPs) previously shown to be active against HIV because of their conversion to ddI through the action of adenosine deaminase was examined in rats. In vitro studies in rat blood and brain tissue homogenate suggested a favorable selectivity for bioconversion in brain tissue, but with bioconversion half-lives varying widely within the series. In vivo infusions of 6 chloro-ddP (6-Cl-ddP), 6-bromo-ddP (6-Br-ddP), and 6-iodo-ddP (6-I-ddP) resulted in significant increases (20- to 34-fold) in the ddI concentration ratios in brain parenchyma/plasma when compared with those after an infusion of ddI alone. Absolute concentrations of ddI in brain parenchyma were increased 10- and 4-fold, respectively, following 30-min infusions of 6-Cl-ddP or 6-Br-ddP, but were 2.4 fold lower after an infusion of 6-I-ddP relative to that after a control infusion of ddI. Detailed studies of the plasma pharmacokinetics, CNS uptake kinetics, and bioconversion of 6-Cl-ddP were conducted to compare in vivo transport and bioconversion parameters with those predicted from in vitro measurements and to rationalize the efficiency of CNS delivery of ddI from 6-Cl-ddP. The results show that increased lipophilicity alone does not ensure that a given prodrug will deliver higher levels of a parent compound to the CNS. Both the selectivity and absolute rate of bioconversion in the brain are important factors. PMID- 1444296 TI - Modes of action and inhibitory activities of new siderophore-beta-lactam conjugates that use specific iron uptake pathways for entry into bacteria. AB - We describe here the mechanism of inhibition of two new siderophore-beta-lactam conjugates against Escherichia coli X580. One conjugate is a spermidine-based catechol siderophore-carbacephalosporin (JAM-2-263), and the other is an N5 acetyl-N5-hydroxy-L-ornithine tripeptide hydroxamate siderophore carbacephalosporin (EKD-3-88). In an agar diffusion test, both conjugates produced large inhibitory zones against strain X580. Resistant strains (i.e., JAMR and EKDR) could be isolated after exposure of X580 to the conjugates JAM-2 263 and EKD-3-88, respectively. No cross-resistance was observed in these individual isolates. JAMR and EKDR were studied further to elucidate the mechanism of inhibition of each conjugated drug. The affinities of JAM-2-263 and EKD-3-88 for penicillin-binding proteins (PBPs) of isolated inner membranes were determined by a competition assay with 125I-penicillin V. JAM-2-263 targeted primarily PBPs 1A/B and 5/6, while EKD-3-88 targeted PBPs 1A/B and 3. Strains X580, JAMR, and EKDR showed similar PBP affinities for the conjugates. However, marked changes were observed in the iron-regulated outer membrane proteins of resistant isolates grown on agar plates depleted of iron. EKDR lost the expression of FhuA (78 kDa) and its sensitivity to phages T1 and T5, whereas JAMR lost the expression of Cir (74 kDa) and its sensitivity to colicin Ia. These results revealed the requirement of FhuA and Cir for the inhibitory activities of EKD-3-88 and JAM-2-263, respectively. In an antibiotic diffusion assay, ferrichrome (1 microM) strongly antagonized the activities of both conjugates against X580 and JAMR, including the residual activity of JAM-2-263 against JAMR. However, the susceptibility of strain EKDR lacking the ferrichrome receptor (FhuA ) to the two conjugates remained the same in the presence of ferrichrome. The antagonistic effect of ferrichrome on the activity of JAM-2-263 may also indicate a role for FhuA in the activity of this beta-lactam conjugate. A FhuA- Cir- double mutant confirmed this hypothesis, since it showed a higher level of resistance to JAM-2-263. To reproduce iron-restricted in vivo growth conditions, we grew X580 and EKDR cells in diffusion chambers implanted in the peritoneal cavities of rats. Strain EKDR showed impaired growth in such a cultivation system. This is the first report of beta-lactam drug transport into E. coli cells that involves the FhuA outer membrane protein. PMID- 1444297 TI - Analysis of multiply antimicrobial-resistant isolates of Streptococcus pneumoniae from the United States. AB - Streptococcus pneumoniae isolates resistant to penicillin, chloramphenicol, tetracycline and sulfamethoxazole-trimethroprim are being recovered with increasing frequency in the United States. We analyzed the penicillin-binding proteins (PBPs), multilocus enzyme electrophoresis (MLEE) genotypes, and ribotypes of 22 multiresistant serotype 23F isolates of S. pneumoniae from the United States and 1 isolate each from Spain and South Africa. Also included were seven multiresistant isolates of other serotypes, three penicillin-resistant but chloramphenicol-susceptible serotype 23F isolates, and two penicillin-susceptible isolates (one penicillin-susceptible isolate was serotype 23F). Fifteen of the 22 multiresistant isolates from the United States and the isolates from Spain and South Africa had identical PBP patterns, MLEE profiles, and ribotypes. Six of the remaining seven multiresistant isolates were related by PBP pattern, but demonstrated slightly different MLEE and/or ribotype profiles, possibly because of acquisition of additional resistance markers (four of the six isolates were also resistant to erythromycin). The remaining multiresistant serotype 23F isolate had a unique PBP pattern and ribotype and was only distantly related to the other pneumococcal isolates by MLEE analysis. The PBP patterns, MLEE profiles, and ribotypes of the multiresistant serotype 23F isolates were easily distinguished from those of six multiresistant isolates of other serotypes; three other penicillin-resistant, chloramphenicol-susceptible, serotype 23F isolates; and two penicillin-susceptible isolates. One exception was a multiresistant serotype 19A isolate that was highly related to the clonal group by PBP pattern and MLEE analysis and that had a ribotype similar to those of the other erythromycin-resistant serotype 23F isolates. MLEE analysis and ribotyping were more discriminating than were the PBP patterns in discerning strain differences. These data strongly suggest that a multiresistant clone of S. pneumoniae serotype 23F that is related to multiresistant isolates from Spain and South Africa has become disseminated in the United States. Clinicians should be alerted to the spread of these multiresistant strains in the United States. PMID- 1444298 TI - Prospective study of oral teicoplanin versus oral vancomycin for therapy of pseudomembranous colitis and Clostridium difficile-associated diarrhea. AB - A prospective, randomized study comparing oral teicoplanin with oral vancomycin in the treatment of pseudomembranous colitis (PMC) and Clostridium difficile associated diarrhea (CDAD) was performed. Teicoplanin was administered at a dosage of 100 mg twice a day for 10 days, and vancomycin was administered at a dosage of 500 mg four times a day for 10 days. CDAD was diagnosed by demonstrating both C. difficile and cytotoxin in the feces of symptomatic patients (more than three loose stools per day). The diagnosis of PMC was also based on colonoscopy. Cytotoxin assay and cultures were checked in all patients 7 to 10 days after discontinuation of therapy and 25 to 30 days thereafter. Of the 51 patients enrolled, 46 were judged to be assessable. Among these, 26 received teicoplanin and 20 received vancomycin. At enrollment, both groups were comparable in terms of age, sex, occurrence of PMC or CDAD, and previous antibiotic treatment. Eighteen of the 20 patients in the vancomycin group and 10 of the 26 patients in the teicoplanin group had previously undergone surgery (P = 0.0004). Treatment resulted in the clinical cure of 20 (100%) vancomycin and 25 (96.2%) teicoplanin patients (P = 0.56). After discontinuation of therapy, clinical symptoms recurred in four (20%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.21). Posttherapy asymptomatic C. difficile carriage (positive follow-up cultures without any clinical symptoms) occurred in five (25%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.11).Overall, 9 of 20 (45%) vancomycin patients and 5 of 26 (19.2%) teicoplanin patients (P=0.059) appeared not to be cleared of C. difficile after treatment. No adverse effects related to vancomycin or teicoplanin therapy were observed. PMID- 1444300 TI - Absence of synergistic activity between ampicillin and vancomycin against highly vancomycin-resistant enterococci. AB - The emergence of clinical enterococcal isolates resistant to both ampicillin and vancomycin is a cause of great concern, as there are few therapeutic alternatives for treatment of infections caused by such organisms. We evaluated the effects of the combination of ampicillin with vancomycin against vancomycin-resistant clinical enterococcal isolates. Using both the checkerboard technique and time kill curves, we examined 28 strains of enterococci (17 Enterococcus faecalis and 11 Enterococcus faecium strains) with different levels of resistance to vancomycin. Of these, 15 strains were also highly gentamicin resistant, and 9 demonstrated resistance to ampicillin. Only seven strains of E. faecalis were inhibited synergistically by the combination of vancomycin with ampicillin, and even then, the concentrations of vancomycin at which synergism was demonstrated were above levels achievable in serum. None of the ampicillin-resistant isolates (all E. faecium) were inhibited synergistically at any concentration of the drugs. In no instance was bactericidal synergism observed, and in most cases the combination resulted in less killing than with ampicillin alone. Antagonism was not observed at clinically relevant concentrations. The results of this study suggest that the combination of vancomycin with ampicillin has little to offer against these emerging pathogens. PMID- 1444299 TI - Antimicrobial susceptibilities and beta-lactamase characterization of Capnocytophaga species. AB - Capnocytophaga species have been associated with a wide variety of infections in both immunocompetent and immunocompromised patients. On the basis of data from antimicrobial susceptibility studies, beta-lactam antibiotics have been considered efficacious therapy. Six of 19 isolates from primarily clinical sources across Canada demonstrated beta-lactamase production, and agar dilution susceptibility testing showed broad resistance to beta-lactam antibiotics. For the beta-lactamase producing isolates, clavulanate reduced the MIC of amoxicillin for 90% of the strains tested by 64-fold. Isolates were highly susceptible to clindamycin, imipenem, and ciprofloxacin. Characterization of the beta-lactamases produced by two of these isolates (Van1 and Van2) was performed. Isoelectric focusing revealed an identical isoelectric point of 5.6 for both enzymes, but they had markedly different relative hydrolysis efficiencies, and different conditions were required to extract the enzymes. This study demonstrates the production of different types of beta-lactamases by Capnocytophaga spp. and suggests the need to screen all clinical isolates of Capnocytophaga spp. for the presence of beta-lactamases. PMID- 1444301 TI - Subcellular localization of tobramycin and vancomycin given alone and in combination in proximal tubular cells, determined by immunogold labeling. AB - The subcellular localization of tobramycin and vancomycin in the renal cortices of rats was determined with ultrathin sections by immunogold labeling. Four groups of four rats each were treated for 10 days with saline (NaCl, 0.9%), tobramycin at dosages of 20 mg/kg of body weight per 12 h intraperitoneally, vancomycin at dosages of 25 mg/kg/12 h subcutaneously, or the combination tobramycin-vancomycin. On day 11, the animals were killed, and cubes of renal cortex were fixed overnight in phosphate-buffered glutaraldehyde (0.5%), dehydrated in ethanol, and embedded in Araldite 502 resin. Ultrathin sections were made and incubated with sheep antitobramycin antibody followed by protein A gold (15-nm diameter) complex or rabbit antivancomycin antibody followed by gold (30-nm diameter)-labeled goat anti-rabbit antibody. For the double labeling, incubations were made on opposite sides of the grid. Tobramycin was detected over the lysosomes of proximal tubular cells, but the labeling was concentrated into small areas in the matrix of the lysosomes. Vancomycin was seen over the lysosomes of proximal tubular cells and was distributed uniformly throughout the matrix of the lysosomes. In rats treated with tobramycin-vancomycin, both drugs were still detected in lysosomes of proximal tubular cells. It is concluded that tobramycin and vancomycin accumulate in lysosomes of proximal tubular cells throughout 10 days of treatment and that vancomycin has no effect on the subcellular distribution of tobramycin. PMID- 1444302 TI - Pharmacodynamic interaction between RP 59500 and gram-positive bacteria infecting fibrin clots. AB - The fibrin clot penetration and in vivo bactericidal activity of RP 59500, a new semisynthetic streptogramin, for two Staphylococcus aureus strains (one methicillin resistant and the other methicillin susceptible), two Staphylococcus epidermidis strains (one methicillin resistant and the other methicillin susceptible), and one Enterococcus faecalis strain were evaluated. The clots, inserted subcutaneously, were infected with a mean of 10(8) CFU of the pathogen per g. For each strain, groups of four rabbits received a single intravenous injection of 50 mg of RP 59500 per kg of body weight over 30 min. The mean peak level of RP 59500 in serum in the infected rabbits was 61.9 +/- 6.3 micrograms/ml. The drug was detectable in serum at a level of 0.8 micrograms/ml up to 4 h after administration. The mean peak fibrin clot drug level at 1 h was 3.3 +/- 0.1 micrograms/g. At 6 h, the level in clots was 1.2 +/- 0.1 micrograms/g. The mean half-life in serum in infected rabbits was 0.34 +/- 0.01 h, while in clots the drug exhibited a longer half-life of 3.8 +/- 0.4 h. In vivo, this new streptogramin sterilized the clots infected with the two S. aureus strains studied in less than 1 h and induced a marked reduction in colony counts of the two S. epidermidis strains studied for up to 24 h. The activity of the streptogramin against E. faecalis was limited. These results suggest that RP 59500 should be further evaluated for the treatment of infection with methicillin resistant staphylococci. PMID- 1444303 TI - Cloning and DNA sequence analysis of an aac(3)-Vb gene from Serratia marcescens. AB - The AAC(3)-V resistance mechanism is characterized by high-level resistance to the aminoglycosides gentamicin, netilmicin, 2'-N-ethylnetilmicin, and 6'-N ethylnetilmicin and moderate resistance levels to tobramycin. Serratia marcescens 82041944 contains an AA(3)-V resistance mechanism as determined from aminoglycoside resistance profiles. This strain, however, does not exhibit hybridization with a probe derived from the previously cloned aac(3)-Va gene, (R. Allmansberger, B. Brau, and W. Piepersberg, Mol. Gen. Genet. 198:514-520, 1985). High-pressure liquid chromatography analysis of the acetylation products of sisomicin carried out by extracts of S. marcescens 82041944 have demonstrated the presence of an AAC(3) enzyme. We have cloned the gene encoding this acetyltransferase and have designated it aac(3)-Vb. Nucleotide sequence comparisons show that the aac(3)-Va and aac(3)-Vb genes are 72% identical. The predicted AAC(3)-Vb protein is 28,782 Da. Comparisons of the deduced amino acid sequences show 75% identity and 84% similarity between the AAC(3)-Va and AAC(3) Vb proteins. The use of a DNA fragment internal to the aac(3)-Vb as a hybridization probe demonstrated that the aac(3)-Vb gene is very rare in clinical isolates possessing an AAC(3)-V mechanism. PMID- 1444304 TI - Serum and blister fluid pharmacokinetics and bactericidal activities of ampicillin-sulbactam, cefotetan, cefoxitin, ceftizoxime, and ticarcillin clavulanate. AB - Ampicillin-sulbactam, ticarcillin-clavulanate, cefoxitin, cefotetan, and ceftizoxime are promoted for the treatment of mixed aerobic-anaerobic bacterial infections. Their activities have been compared in vitro but not in vivo. In order to assess the in vivo activities of these agents in serum and interstitial fluid, we administered single, intravenous doses of these antimicrobial agents to healthy subjects. Concentrations of the antimicrobial agents in serum and suction induced blister fluid and bactericidal activity were measured by high-pressure liquid chromatography and the standard methodology of the National Committee for Clinical Laboratory Standards, respectively. The organisms used for bactericidal activity tests were one isolate each of Staphylococcus aureus, Klebsiella pneumoniae, and Bacteroides fragilis. Pharmacokinetic parameters in serum and blister fluid were similar to those derived in other investigations. Of note were the high and prolonged concentrations of ticarcillin and cefotetan in blister fluid, despite high-level serum protein binding. The bactericidal activities in serum and blister fluid reflected the relative in vitro activities and kinetic dispositions of the various antimicrobial agents except for the bactericidal activity of cefotetan, which was substantially lower in blister fluid than serum, despite a blister fluid:serum area under the concentration-time curve ratio of 1.5. Similarly, the activity of ticarcillin-clavulanate in blister fluid was also substantially less than would have been predicted by the blister fluid:serum ratio of the area under the concentration-time curve of 1.1, possibly because of the low concentrations of clavulanate in blister fluid. The rankings of the in vivo bactericidal activities of the five drugs were as follows: for S. aureus, ampicillin-sulbactam > ticarcillin-clavulanate > ceftizoxime > cefoxitin > cefotetan; for K. pneumoniae, ceftizoxime > cefotetan > ampicillin-sulbactam = ticarcillin-clavulanate > cefoxitin; and for B.fragilis, ticarcillin-clavulanate > cefotetan > ceftizoxime > ampicillin-sulbactam = cefoxitin. PMID- 1444305 TI - Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B. AB - Using an in vitro model of intravascular infection, we examined the effects of exposure to subinhibitory concentrations of fluconazole and amphotericin B on the ability of Candida albicans to adhere to and damage human umbilical vein endothelial cells. Incubation of the organisms for 18 h in 0.5x the MICs of fluconazole and amphotericin B inhibited endothelial cell adherence by 22 and 91%, respectively (P less than 0.001 for each drug). Candida-induced endothelial cell injury was also decreased by exposing the organisms to the antifungal drugs while in contact with the endothelial cells. Fluconazole inhibited damage by approximately 50% at concentrations ranging from 0.25x to 5x the MIC (P less than 0.01 for each concentration). Exposure to amphotericin B at 0.5x the MIC completely blocked the ability of the organisms to injure endothelial cells. The capacities of the antifungal agents to inhibit endothelial cell injury paralleled their abilities to suppress candidal germination. Organisms exposed to up to 5x the MIC of fluconazole had diminished, but still detectable, germ tube production and elongation, whereas incubation in 0.5x the MIC of amphotericin B completely abrogated germination. In addition to their direct effects on the growth of C. albicans, fluconazole and amphotericin B may decrease the ability of the fungus to disseminate hematogenously by inhibiting the organisms' capacity to adhere to and injure endothelial cells. PMID- 1444306 TI - Intravenous and oral zidovudine pharmacokinetics and coagulation effects in asymptomatic human immunodeficiency virus-infected hemophilia patients. AB - Pharmacokinetic and coagulation studies were carried out over a 12-week period with 11 asymptomatic hemophilia patients with human immunodeficiency virus infection receiving zidovudine (ZDV). The patients received 300 mg every 4 h while awake (the accepted dose at the time of this study); consecutive 24-h intravenous (i.v.) and 12-h oral pharmacokinetic studies were conducted at weeks 1, 6, and 12. Coagulation studies were conducted at weeks 0, 4, 8, and 12. The numbers of units of factors VIII and IX and cryoprecipitate transfused during the 12-week periods before, during, and after ZDV treatment were recorded. Following i.v. and oral ZDV administration, the concentration in plasma declined rapidly over the first 4 h, and in some patients, ZDV was still detectable at 4 to 10 h. The i.v. total clearances (means +/- standard deviations) were 14.9 +/- 7.3, 11.2 +/- 3.7, and 15.1 +/- 4.7 ml/min/kg of body weight. The i.v. distribution volumes were 1.08 +/- 0.5, 1.0 +/- 0.4, and 1.65 +/- 1.4 liters/kg. The bioavailabilities were 0.54 +/- 0.22, 0.46 +/- 0.19, and 0.59 +/- 0.13 at weeks 1, 6, and 12, respectively. The pattern of ZDV-glucuronide (GZDV) disposition was similar to that of ZDV, and the peak plasma GZDV-to-ZDV ratio was higher after oral dosing, consistent with first-pass metabolism. In some individuals, up to 33% of an i.v. dose was excreted unchanged. At weeks 6 and 12, greater than 300 mg of total ZDV (GZDV plus ZDV) was recovered in the urine of some patients, suggesting tissue redistribution. Concentration in plasma after oral ZDV administration were variable, both within and between patients. The von Willebrand antigen level consistently decreased throughout the study but was not accompanied by a parallel change in ristocetin cofactor A activity, and no clinical adverse effects on coagulation were noted. This study demonstrates that ZDV can be used in hemophilia patients without worsening of their bleeding tendencies. The clinical significance of decreased ZDV clearance and the prolonged terminal elimination phase of ZDV will require further study with patients receiving chronic ZDV. PMID- 1444307 TI - Sequence analysis of the beta-lactamase repressor from Staphylococcus aureus and hybridization studies with two beta-lactamase-producing isolates of Enterococcus faecalis. AB - The putative beta-lactamase (Bla) repressor gene, blaI, from the staphylococcal plasmid pI524 was isolated, and the DNA sequence was determined. The sequence of blaI was found to be identical to the blaI sequence from pI9789 (blaI blaZ seg 1), a plasmid related to pI524. A blaI probe from pI524 was hybridized with plasmid and genomic DNA from Bla+ Enterococcus faecalis isolates HH22 and PA. The Bla structural gene of HH22 has been previously shown to be of staphylococcal origin, but DNA homologous to the staphylococcal Bla repressor was not found, indicating that the constitutive production of beta-lactamase in these E. faecalis isolates may be the result of a missing repressor protein. PMID- 1444308 TI - Effects of antacids, ferrous sulfate, and ranitidine on absorption of DR-3355 in humans. AB - This study examined the effects of widely used antacids (aluminum hydroxide, magnesium oxide, and calcium carbonate), ferrous sulfate, and ranitidine on the absorption of a fluorinated quinolone, (-)-(S)-9-fluoro-3-methyl-10-(4-methyl-1 piperazinyl)-7-oxo-2,3-dihydro- 7H- pyrido-[1,2,3,-de][1,4]benzoxazine-6 carboxylic acid hemihydrate (DR-3355), in healthy male volunteers enrolled in three separate randomized crossover studies. Study 1 used 100-mg doses of DR-3355 and concurrent doses of aluminum hydroxide (1 g) or magnesium oxide (500 mg), while study 2 used DR-3355 (100 mg) and concurrent ferrous sulfate (160 mg) or calcium carbonate (1 g). Study 3 used DR-3355 (100 mg) and concurrent ranitidine (150 mg). Each study included control doses of DR-3355 (100 mg) alone. When aluminum hydroxide, ferrous sulfate, and magnesium oxide were coadministered with DR-3355, the relative bioavailability of DR-3355 was decreased to 56, 81, and 78%, respectively, of that for DR-3355 (100 mg) alone. Urinary excretion of DR 3355 was also significantly decreased by coadministration of these drugs. Thus, the magnitude of the decrease in the area under the concentration-time curve for DR-3355 varied among antacids, and the ranking of their inhibitory effects correlated with previously reported rankings of stability constants for chelate formation. DR-3355 bioavailability was not influenced by the concurrent administration of calcium carbonate and ranitidine, indicating that changes in gastric pH do not affect DR-3355 absorption. PMID- 1444309 TI - Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production. AB - Recent reports have demonstrated an immunomodulating activity of dehydroepiandrosterone (DHEA) different from that described for glucocorticoids. The present study was designed to test DHEA's activity in endotoxic shock and to investigate its effect on endotoxin-induced production of tumor necrosis factor (TNF). Mortality of CD-1 mice exposed to a lethal dose of lipopolysaccharide (LPS; 800 micrograms per mouse) was reduced from 95 to 24% by treatment with a single dose of DHEA, given 5 min before LPS. LPS administration resulted in high levels of TNF, a response that was significantly blocked by DHEA, both in vivo and in vitro. DHEA treatment also reduced LPS-induced increments in serum corticosterone levels, a parameter considered not to be mediated by TNF. In another experimental model, mice sensitized with D-galactosamine, followed by administration of recombinant human TNF, were subjected to 89% mortality rate, which was reduced to 55% in DHEA-treated mice. These data show that DHEA protects mice from endotoxin lethality. The protective effect is probably mediated by reduction of TNF production as well as by effecting both TNF-induced and non-TNF induced phenomena. PMID- 1444310 TI - Pharmacokinetics of 18F-labeled fleroxacin in rabbits with Escherichia coli infections, studied with positron emission tomography. AB - 18F-labeled fleroxacin was used to measure the pharmacokinetics of fleroxacin in healthy and infected animals by positron emission tomography (PET) and tissue radioactivity measurements. In all experiments, a pharmacological dose of unlabeled drug (10 mg/kg) was coinjected with the tracer. The pharmacokinetics of [18F]fleroxacin was measured in groups of healthy mice (n = six per group) at 10, 30, 60, and 120 min after injection and in groups of rats with Escherichia coli thigh infections (n = six per group) at 60 and 120 min after injection by radioactivity measurements in excised tissues. In healthy rabbits (n = 4) and in rabbits with E. coli thigh infections (n = 4), tissue concentrations of drug were determined by serial PET imaging over 2 h; after the final image was acquired, animals were sacrificed and concentrations measured by PET were compared with the results of tissue radioactivity measurements. In all three species, there was rapid equilibration of [18F]fleroxacin to significant concentrations in most peripheral organs; low concentrations of drug were detected in the brain. Accumulations of radiolabeled drug in infected and healthy thigh muscles were similar. Peak concentrations of drug of more than three times the MIC for 90% of members of the family Enterobacteriaceae (greater than 100-fold for most organisms) were achieved in all tissues except brain and remained above this level for more than 2 h. Especially high peak concentrations were achieved in the kidney (greater than 75 micrograms/g), liver (greater than 50 micrograms/g), blood (greater than 25 micrograms/g), and bone and lung (greater than 10 micrograms/g). Since the MICs for 90% of all Enterobacteriaceae are <2 micrograms/ml, fleroxacin should be particularly useful in treating gram-negative infections affecting these tissues. In contrast, the low concentration of drug delivered to the brain should limit the toxicity of the drug for the central nervous system. PMID- 1444311 TI - Effects of the aggregation state of amphotericin B on its toxicity to mice. AB - Amphotericin B (AmB) is a very effective antifungal agent for most systemic fungal infections. However, the relatively high toxicity of this drug imposes limits on its clinical usefulness. Most of the current work in this field is devoted to the search for less-toxic formulations of the drug. Here we describe the effects of three surfactants, one anionic and the other two nonionic, on the aggregation state of AmB in solutions which were injected intravenously into mice. The degree of aggregation of AmB was monitored spectroscopically and by light scattering. The toxicity was expressed as percentage of survivors. These results were compared with those obtained with doses of AmB the same as those present in a commercial formulation of AmB, Fungizone. Two surfactants, lauryl sucrose and sodium deoxycholate, used at concentrations which induced monomerization of AmB, substantially decreased the acute toxicity of AmB to mice. Conversely, the third surfactant, Tween 80, showed a synergistic potentiation of the toxicity of the antibiotic. A good correlation was found between the in vivo toxicity and the aggregation state of AmB in injected solutions. Solutions in which AmB was almost entirely monomeric were half as toxic after 24 h and about six times less toxic after 1 week than the corresponding solutions of Fungizone. PMID- 1444312 TI - Use of Tn5lac to study expression of genes required for production of the antibiotic TA. AB - The beta-galactosidase activities arising from Tn5lac insertions in several genes required for antibiotic TA production were measured under different growth conditions. In all of the non-TA-producing mutants, the beta-galactosidase specific activity was higher when the cells were grown in nutrient-limited 0.5CTS medium (0.5% Casitone plus alanine, serine, and glucose) than in rich 2CT medium (2% Casitone). One of the mutants, 420, had low beta-galactosidase specific activity in both media. The other seven mutants containing inserts in genes essential for TA production had specific activities of 139 to 367 U/mg of protein in 0.5CTS medium and 11 to 48 U/mg of protein in 2CT medium. The beta galactosidase specific activities of two strains, 1030 and 420, increased during exponential growth in 0.5CTS medium. The beta-galactosidase specific activities of both strains increased greatly when the cells were grown in the presence of magnesium phosphate, which traps ammonium ions. The Tn5lac insertions in 1030 and 420 were used to screen for mutants with increased levels of transcription. An N methyl-N'-nitro-N-nitrosoguanidine-induced mutation in 1030 that mapped 17 kb from the omega 1010 insert increased the specific activity of beta-galactosidase 21 times in 2CT medium. The regulatory mutation appears to release the repression caused by 2CT medium. A UV-induced mutation in 420 increased the beta galactosidase specific activity 1.4 to 2.4 times. Medium conditions that affect the transcription of TA genes are discussed in terms of enhanced antibiotic TA production. PMID- 1444313 TI - Low-dose trimethoprim-sulfamethoxazole alone and in association with zidovudine for prevention and treatment of murine Pneumocystis carinii pneumonia. AB - Low-dose trimethoprim-sulfamethoxazole (TMP-SMX) alone was found to be as effective as low-dose TMP-SMX plus zidovudine and standard-dose TMP-SMX alone in preventing and treating Pneumocystis carinii pneumonia (PCP) in an immunosuppressed-rat model. Zidovudine alone had no preventive or curative effect on PCP. We conclude that the initially reported reduced incidence of PCP in human immunodeficiency virus-infected patients treated with zidovudine alone is not due to anti-P. carinii activity of zidovudine. Furthermore, the clinical efficacy of low-dose TMP-SMX for the prevention and treatment of PCP should be further investigated. PMID- 1444314 TI - Effects of diclofenac on ceftriaxone pharmacokinetics in humans. AB - The effects of diclofenac, a nonsteroidal antiinflammatory drug, on the biliary and urinary excretion of ceftriaxone were evaluated in subjects with a T drain in the common bile duct. The kinetic study was carried out on the sixth postoperative day of treatment with ceftriaxone alone (2 g intravenously; group 1) or ceftriaxone combined with diclofenac (50 mg every 12 h orally from postoperative days 3 to 6; group 2). A significant increase in the elimination half-life of ceftriaxone was observed in group 2 patients. Diclofenac caused a significant rise in ceftriaxone biliary excretion. This increase was not sufficient to balance the significant deficit of urinary excretion of ceftriaxone. PMID- 1444315 TI - In vivo expression of in vitro anticoccidial activity. AB - Large-scale screening has led to the identification of several experimental compounds that have very potent intrinsic activity against coccidia, but the lack of translation to in vivo efficacy has been a major hurdle in developing such leads into effective new drugs. We developed methods to explore the impact of oral availability and appropriate distribution in tissue, both of which are potentially important factors in the expression of activity in vivo. For the compounds that we examined, neither oral absorption nor distribution to the site of infection appeared to be the critical barrier to in vivo expression of intrinsic anticoccidial activity. Elucidation of the nature of additional factors that might be involved could assist greatly in the identification of useful new anticoccidial agents. PMID- 1444317 TI - Activities of newer fluoroquinolones against Shigella sonnei. AB - The activities of six fluoroquinolones were determined for 117 separate strains of Shigella sonnei. The order of increasing activity (MICs for 90% of strains tested) was enoxacin (0.25 micrograms/ml), temafloxacin (0.032 micrograms/ml), sparfloxacin (0.016 micrograms/ml), CI-960 (0.008 micrograms/ml), ciprofloxacin (0.008 micrograms/ml), and PD-131628-2 (0.008 micrograms/ml). These data, along with results of killing and mutational rate studies, showed that all six fluoroquinolones were highly inhibitory against S. sonnei and five fluoroquinolones were rapidly and persistently bactericidal. PMID- 1444316 TI - Bactericidal activity of ramoplanin against antibiotic-resistant enterococci. AB - Ramoplanin, a new lipoglycodepsipeptide antibiotic, was uniformly active against 65 strains of enterococci, including strains highly resistant to vancomycin, penicillin G, and gentamicin. MBCs were usually within a fourfold dilution of the MICs. In time-kill studies, ramoplanin alone demonstrated dose-dependent bactericidal activity against enterococcal strains that resisted killing by vancomycin or penicillin in combination with gentamicin. PMID- 1444318 TI - Phase I study of antilipopolysaccharide human monoclonal antibody MAB-T88. AB - Monoclonal antibody MAB-T88 is a human monoclonal immunoglobulin M antibody directed at the lipopolysaccharide of gram-negative bacteria. In this study, nine patients who were expected to become neutropenic from antineoplastic chemotherapy received an infusion of MAB-T88, three patients at each of three doses: 1, 4, and 8 mg/kg of body weight. MAB-T88 was shown to be safe, with an effective half-life in plasma of 25.4 h, and no patient developed immunoglobulin G antibody to MAB T88. PMID- 1444319 TI - Ticarcillin-clavulanic acid zone size criteria. PMID- 1444320 TI - Novel nucleoside strategies for anti-HIV and anti-HSV therapy. AB - This mini-review describes the structure-activity relationships of several series of new nucleoside analogues. It also points to the possibilities of finding new molecular modifications which could lead to antivirals with activity both against human immunodeficiency viruses (HIV) and herpesviruses. PMID- 1444321 TI - Anti-HIV-1 activity of 3'-azido-3'-deoxythymidine (AZT) in primary mononuclear phagocytes. AB - Conflicting data have been reported on ability of 3'-azido-3'-deoxythymidine (AZT) to protect mononuclear phagocytes from HIV-1 infection. We compared the antiviral potency of AZT in three types of primary human mononuclear phagocytes: peripheral blood monocytes, monocyte-derived macrophages (in vitro differentiated) and alveolar macrophages (in vivo differentiated). To establish highly-productive virus infection, purified cells (greater than 99%) from healthy donors were challenged with the macrophage-tropic HTLV-IIIBa-L strain at input multiplicities ranging from 0.05 to 20 TCID50 per cell. AZT (0.1 nM-10 microM) was added immediately after infection and either continued for the duration of the experiment or stopped 1-7 days after infection. The kinetics of HIV-1Ba-L replication were assessed by measuring p24 antigen production on days 4-28 post infection. Continuous treatment with AZT reproducibly inhibited viral replication in a concentration-dependent manner in all three cell types. The IC90 of AZT was 0.04 microM in blood monocytes, 0.009 microM in monocyte-derived macrophages, and 0.0001 microM in alveolar macrophages (mean of 3-4 donors for each cell type). AZT was not cytotoxic at less than 10 microM as assessed by cell viability, cell protein, and interferon-gamma-activated H2O2-release. In experiments in which AZT treatment was stopped after infection, viral replication resumed after a lag of 7 14 days and increased exponentially toward control levels. This occurred despite initial inhibition of virus production to below the limit of p24 detection (approximately 50 pg/ml). These results indicate that AZT is a potent inhibitor of HIV-1 replication in primary mononuclear phagocytes regardless of the stage of cell differentiation, and that AZT is most active in tissue (alveolar) macrophages. AZT does not irreversibly block infection of mononuclear phagocytes, however, as viral replication resumes after removal of AZT. PMID- 1444322 TI - Use of a standardized cell culture assay to assess activities of nucleoside analogs against hepatitis B virus replication. AB - A cell culture system for the evaluation of compounds which inhibit HBV replication (Korba and Milman, Antiviral Res. 15:217, 1991) has been developed into a standardized assay. Toxicity of test compounds was assessed by the uptake of neutral red dye under culture and treatment conditions which were identical to those used for the antiviral assays. A total of 667 separate cultures of 2.2.15 cells were evaluated for this study. In 86 untreated cell cultures, representing 15 experiments over a 24-month period, the levels of extracellular HBV virion DNA and intracellular HBV DNA forms were found to vary by less than 2.5-fold overall. Virion DNA in serum and intracellular viral DNA replication intermediates [RI] are the two most reliable and commonly followed markers of hepadnavirus replication in patients and experimental animals. In these assays, levels of extracellular HBV virion DNA and intracellular HBV RI were well correlated in 2.2.15 cells. Less correlation was observed between the levels of HBV virion DNA and the 3.2-kb episomal HBV genomes present in the cells. A threshold level of 22 37 intracellular replicating HBV genomes appeared to be required before virions were detected in the culture medium. The activities of several 2'-substituted and 3'-substituted deoxynucleoside analogs against HBV replication were compared using this standardized assay. Dideoxycytosine [ddC] and dideoxyguanosine [ddG] were the most selective 2',3'-dideoxynucleosides against HBV in 2.2.15 cells. Substitution of fluorine at the 2' position abolished the antiviral activity of ddC, but enhanced the selective antiviral activities of dideoxythymidine and dideoxyuracil. Several 2'-fluorinated pyrimidine arabinosyl furanosides, reported to be potent (but toxic) inhibitors of hepadnaviruses in vivo, demonstrated relatively low selective antiviral activities in 2.2.15 cells. The current data base allows for validation of any given set of test evaluations through statistical analysis of both the positive and the negative treatment controls present in each experiment; thus, relevant comparisons of the selectivity of anti HBV activities for different compounds examined in future experiments can be made. PMID- 1444323 TI - Zidovudine inhibits hepatitis B virus replication. AB - Hepatitis B virus DNA polymerase is a viral enzyme that can use viral DNA as well as viral RNA as a template for DNA synthesis. Since both activities are essential for the production of new virus particles, blocking of this enzyme should reduce viral replication. In the present study the in vitro effect of zidovudine triphosphate on hepatitis B virus DNA polymerase activity and the in vivo effect of zidovudine on viral replication in chronic HBsAg-positive patients are investigated. Zidovudine triphosphate inhibited in vitro DNA polymerase activity by 50% at a concentration of 0.3 microM. Serum DNA polymerase activity was significantly reduced in 7 patients who received zidovudine (200 mg orally 4 times daily) for one week. A dose-response effect was suggested by the results found for 6 patients who received 100 mg, 200 mg and 300 mg orally 4 times daily for one week with 2 drug-free weeks between each course. We conclude that zidovudine may be of value for non-responders to alpha-interferon therapy or patients with high initial levels of viral replication prior to the start of interferon treatment. PMID- 1444324 TI - Unexpected adverse reactions during a clinical trial in rural west Africa. AB - Ribavirin has been used widely in various clinical trials, without significant adverse effects beyond reversible, mild anemia. Since 1978 intravenous ribavirin has been used to treat Lassa fever in a remote area of Eastern Sierra Leone, West Africa. In March 1991, brief episodes of rigors in patients receiving ribavirin were reported. An immediate investigation found that 27/93 patients (29%) had records in 1990/91 of at least one episode, the strongest association being with survival of Lassa fever (P = 0.0001). The occurrence or number of rigors in an individual patient was unassociated with sex, age, weight, volume of loading dose, cumulative dose, administration of other drugs, use of intravenous lines or heparin traps. In a review of 12 years of ribavirin administration, 74/2117 injections sampled (3.5%) were associated with a record of rigors. Most occurred before 08.00 h (P less than 0.0001), between 0 and 30 min after injection, lasted 2-45 min, and clustered towards the end of the treatment course (P less than 0.0001). There was no association with drug lot or individual vials. Drug was being given as a bolus (less than 1 min). Since slowing the infusion rate, no further episodes have been reported. Epidemiologic techniques are important tools in rapid assessment of unexpected events particularly when conducting trials in remote locations. PMID- 1444325 TI - New hypoxanthine nucleosides with RNA antiviral activity. AB - A series of novel C-2 functionalized hypoxanthine and purine ribonucleosides have been synthesized and evaluated against exotic RNA viruses of the family or genus alpha, arena, flavi, and rhabdo. Both specific and broad-spectrum antiviral activities were discovered but only with hypoxanthine nucleosides. PMID- 1444326 TI - Animal models for anti-AIDS therapy. AB - Primate and non-primate species have been used to study the pathobiology of the simian immunodeficiency virus (SIV) and of the human immunodeficiency virus type 1 (HIV-1), respectively, and to develop new therapeutic regimes. Transgenic mice which express either the entire HIV-1 provirus or subgenomic fragments have been used to analyze viral gene products in vivo and may serve as models for the development of agents targeted to select viral functions. Chimeric mice which were created by transplanting human hematolymphoid cells into mice suffering from congenital severe combined immunodeficiency (scid/scid or so called SCID mice), can be infected with HIV-1 and allow one to study the entire HIV-1 replicative cycle. Type C murine leukemia virus models have been used to develop new prophylactic and therapeutic strategies but their use is restricted to the evaluation of select antiviral drug inhibition, targeted to retroviral genes common to both Lentivirinae and Oncovirinae. The role of various animal model systems in the development of anti-HIV-1 and anti-AIDS therapies is summarized. PMID- 1444327 TI - In vivo anti-influenza virus activity of plant flavonoids possessing inhibitory activity for influenza virus sialidase. AB - Isoscutellarein (5,7,8,4'-tetrahydroxyflavone) from the leaf of Scutellaria baicalensis non-competitively inhibited (IC50, 20 microM) the hydrolysis of sodium p-nitrophenyl-N-acetyl-alpha-D-neuraminate by influenza virus sialidase with an apparent Ki value of 41 microM. Negligible inhibitory activity was observed for mouse liver sialidase at a concentration of 79 microM. Isoscutellarein also inhibited the replication of influenza virus A/WSN/33 in Madin-Darby bovine kidney cells with 50% virus inhibitory dose at 16 nmol/well and influenza virus A/PR/8/34 in the allantoic sac of embryonated egg with little toxic effects. The flavone showed significant anti-influenza virus activity in vitro similar to isoscutellarein-8-methylether (F36) (Nagai, T., Miyaichi, Y., Tomimori, T., Suzuki, Y. and Yamada H., 1990, Chem. Pharm. Bull. 38, 1329-1332), and more potent virucidal activity in ovo than F36. However, F36 completely prevented proliferation of mouse-adapted influenza virus A/PR/8/34 in mouse lung by the intranasal (0.5 mg/kg) and intraperitoneal (4 mg/kg) administrations, and it was more potent than the known anti-influenza virus substance, amantadine. Intranasal administration of F36 (0.5 mg/kg) also protected mice against a lethal influenza virus A/PR/8/34 infection. Isoscutellarein significantly inhibited lung virus proliferation when administered intranasally or orally to mice. F36 and isoscutellarein showed negligible toxic effect against mice. These results suggested that flavones, which have potent influenza virus sialidase inhibitory activity, have anti-influenza virus activity in vivo. PMID- 1444328 TI - Murine retroviral disease-enhancing effects of a pyrimidinone immunomodulator. AB - (B10.A x A/WySn)F1 mice, infected with the Friend virus (FV) complex, were used as a predictive therapeutic model for AIDS. These infected mice exhibit many of the viral and immunologic manifestations of AIDS. Bropirimine (2-amino-5-bromo-6 phenyl-4[3H]pyrimidinone, ABPP) is an immunomodulating compound which has been shown to inhibit other viral infections. Oral (per os treatment) dosages of ABPP ranging from 50 to 400 mg/kg/day for 3 days resulted in increased numbers of infectious centers in the infected mice and increased splenomegaly and percentage of Ig+ (B cells) in spleens of infected and uninfected mice. Decreased percentages of total Thy-1.2+ (total T) cells and L3T4+ (T-helper) cells were seen in both uninfected and infected mice and a slightly decreased percentage of Ly-2+ (T-suppressor/cytotoxic) cells was observed in spleens of the infected mice. No effect on Ly2+ cells in spleens of uninfected mice was found. Intraperitoneal injection, single or multiple, of 20-200 mg/kg ABPP prior to FV injection resulted in increased spleen weights but had no effect on numbers of infectious centers in the spleens or on FV antibody titers in the plasma. Intraperitoneal treatment of uninfected mice with ABPP resulted in slight or no changes in percentages of Thy-1.2+, L3T4+ and Ly-2+ cells. Mice receiving multiple exposures of ABPP had an increase in percentage of splenic B cells and a depressed response to the T cell mitogen PHA. Treatment with ABPP induced the production of interferon (IFN); however, a state of hyporesponsive IFN production was seen following multiple administrations of ABPP. These data suggest that the immunomodulator ABPP may have an enhancing effect on this retroviral disease. PMID- 1444330 TI - Special issue: Molecular biology of Saccharomyces. PMID- 1444329 TI - Rational approaches to the design of antiviral agents based on S-adenosyl-L homocysteine hydrolase as a molecular target. PMID- 1444331 TI - The RAS-adenylate cyclase pathway and cell cycle control in Saccharomyces cerevisiae. AB - The cell cycle of Saccharomyces cerevisiae contains a decision point in G1 called 'start', which is composed of two specific sites. Nutrient-starved cells arrest at the first site while pheromone-treated cells arrest at the second site. Functioning of the RAS-adenylate cyclase pathway is required for progression over the nutrient-starvation site while overactivation of the pathway renders the cells unable to arrest at this site. However, progression of cycling cells over the nutrient-starvation site does not appear to be triggered by the RAS-adenylate cyclase pathway in response to a specific stimulus, such as an exogenous nutrient. The essential function of the pathway appears to be limited to provision of a basal level of cAMP. cAMP-dependent protein kinase rather than cAMP might be the universal integrator of nutrient availability in yeast. On the other hand stimulation of the pathway in glucose-derepressed yeast cells by rapidly-fermented sugars, such as glucose, is well documented and might play a role in the control of the transition from gluconeogenic growth to fermentative growth. The initial trigger of this signalling pathway is proposed to reside in a 'glucose sensing complex' which has both a function in controlling the influx of glucose into the cell and in activating in addition to the RAS-adenylate cyclase pathway all other glucose-induced regulatory pathways in yeast. Two crucial problems remaining to be solved with respect to cell cycle control are the nature of the connection between the RAS-adenylate cyclase pathway and nitrogen-source induced progression over the nutrient-starvation site of 'start' and second the nature of the downstream processes linking the RAS-adenylate cyclase pathway to Cyclin/CDC28 controlled progression over the pheromone site of 'start'. PMID- 1444332 TI - Genetic approaches to the study of mitochondrial biogenesis in yeast. AB - In contrast to most other organisms, the yeast Saccharomyces cerevisiae can survive without functional mitochondria. This ability has been exploited in genetic approaches to the study of mitochondrial biogenesis. In the last two decades, mitochondrial genetics have made major contributions to the identification of genes on the mitochondrial genome, the mapping of these genes and the establishment of structure-function relationships in the products they encode. In parallel, more than 200 complementation groups, corresponding to as many nuclear genes necessary for mitochondrial function or biogenesis have been described. Many of the latter are required for post-transcriptional events in mitochondrial gene expression, including the processing of mitochondrial pre RNAs, the translation of mitochondrial mRNAs, or the assembly of mitochondrial translation products into the membrane. The aim of this review is to describe the genetic approaches used to unravel the intricacies of mitochondrial biogenesis and to summarize recent insights gained from their application. PMID- 1444333 TI - Global regulators of chromosome function in yeast. AB - In the yeast Saccharomyces cerevisiae, several abundant, sequence-specific DNA binding proteins are involved in multiple aspects of chromosome function. In addition to functioning as transcriptional activators of a large number of yeast genes, they are also involved in transcriptional silencing, the initiation of DNA replication, centromere function and regulation of telomere length. This review will consider each of these proteins, focusing on what is known about the mechanisms of their multiple functions. PMID- 1444334 TI - Nuclear transport and nuclear pores in yeast. AB - The central features of nuclear import have been conserved during evolution. In yeast the nuclear accumulation of proteins follows the same selective and active transport mechanisms known from higher eukaryotes. Yeast nuclear proteins contain nuclear localization sequences (NLS) which are presumably recognized by receptors in the cytoplasm and the nuclear envelope. Subsequent to this recognition step, nuclear proteins are translocated into the nucleus via the nuclear pore complexes. The structure of the yeast nuclear pore complex resembles that of higher eukaryotes. Recently, the first putative components of the yeast nuclear import machinery have been cloned and sequenced. The genetically amenable yeast system allows for an efficient structural and functional analysis of these components. Due to the evolutionary conservation potential insights into the nuclear import mechanisms in yeast can be transferred to higher eukaryotes. Thus, yeast can be considered as a eukaryotic model system to study nuclear transport. PMID- 1444335 TI - The genetics of nuclear pre-mRNA splicing: a complex story. AB - The occurrence of introns in nuclear precursor RNAs (pre-mRNAs) is widespread in eukaryotes, and the splicing process that removes them is basically the same in yeasts as it is in higher eukaryotes. Splicing takes place in a very large, multi component complex, the splicesome, and biochemical studies have been complicated by the large number of splicing factors involved. This review describes how genetic approaches used to study RNA splicing in Saccharomyces cerevisiae have complemented the biochemical studies and led to rapid advances in the field. PMID- 1444336 TI - Molecular biology of translation in yeast. AB - The combination of genetic, molecular and biochemical approaches have made the yeast Saccharomyces cerevisiae a convenient organism to study translation. The sequence similarity of translation factors from yeast and other organisms suggests a high degree of conservation in the translational machineries. This view is also strengthened by a functional analogy of some proteins implicated in translation. Beautiful genetic experiments have confirmed existing models and added new insights in the mechanism of translation. This review summarizes recent experiments using yeast as a model system for the analysis of this complex process. PMID- 1444337 TI - Peroxisome biogenesis in Saccharomyces cerevisiae. AB - The observation that peroxisomes of Saccharomyces cerevisiae can be induced by oleic acid has opened the possibility to investigate the biogenesis of these organelles in a biochemically and genetically well characterized organism. Only few enzymes have been identified as peroxisomal proteins in Saccharomyces cerevisiae so far; the three enzymes involved in beta-oxidation of fatty acids, enzymes of the glyoxylate cycle, catalase A and the PAS3 gene product have been unequivocally assigned to the peroxisomal compartment. However, more proteins are expected to be constituents of the peroxisomes in Saccharomyces cerevisiae. Mutagenesis of Saccharomyces cerevisiae cells gave rise to mutants unable to use oleic acid as sole carbon source. These mutants could be divided in two groups: those with defects in structural genes of beta-oxidation enzymes (fox-mutants) and those with defects in peroxisomal assembly (pas-mutants). All fox-mutants possess morphologically normal peroxisomes and can be assigned to one of three complementation groups (FOX1, 2, 3). All three FOX genes have been cloned and characterized. The pas-mutants isolated are distributed among 13 complementation groups and represent 3 different classes: peroxisomes are either morphologically not detectable (type I) or present but non-proliferating (type II). Mislocalization concerns all peroxisomal proteins in cells of these two classes. The third class of mutants contains peroxisomes normal in size and number, however, distinct peroxisomal matrix proteins are mislocalized (type III). Five additional complementation groups were found in the laboratory of H.F. Tabak. Not all PAS genes have been cloned and characterized so far, and only for few of them the function could be deduced from sequence comparisons. Proliferation of microbodies is repressed by glucose, derepressed by non-fermentable carbon sources and fully induced by oleic acid. The regulation of four genes encoding peroxisomal proteins (PAS1, CTA1, FOX2, FOX3) occurs on the transcriptional level and reflects the morphological observations: repression by glucose and induction by oleic acid. Moreover, trans-acting factors like ADR1, SNF1 and SNF4, all involved in derepression of various cellular processes, have been demonstrated to affect transcriptional regulation of genes encoding peroxisomal proteins. The peroxisomal import machinery seems to be conserved between different organisms as indicated by import of heterologous proteins into microbodies of different host cells. In addition, many peroxisomal proteins contain C-terminal targeting signals. However, more than one import route into peroxisomes does exist.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1444338 TI - Heterologous protein production in yeast. AB - The exploitation of recombinant DNA technology to engineer expression systems for heterologous proteins represented a major task within the field of biotechnology during the last decade. Yeasts attracted the attention of molecular biologists because of properties most favourable for their use as hosts in heterologous protein production. Yeasts follow the general eukaryotic posttranslational modification pattern of expressed polypeptides, exhibit the ability to secrete heterologous proteins and benefit from an established fermentation technology. Aside from the baker's yeast Saccharomyces cerevisiae, an increasing number of alternative non-Saccharomyces yeast species are used as expression systems in basic research and for an industrial application. In the following review a selection from the different yeast systems is described and compared. PMID- 1444339 TI - The pheromone signal pathway in Saccharomyces cerevisiae. AB - Haploid cells of the yeast Saccharomyces cerevisiae normally undergo a budding life cycle, but after binding the appropriate mating pheromone they undergo a different developmental pathway that leads to conjugation. This intercellular communication between the two mating types activates a signal transduction pathway that stimulates the diverse physiological changes required for conjugation, such as induction of cell surface agglutinins, cell division arrest in G1, morphogenesis to form a conjugation tube, and cell fusion. The components of this pathway include a G protein-coupled receptor, several protein kinases, and a pheromone-responsive transcription factor. The molecular mechanisms that transduce the pheromone signal are remarkably similar to the mechanisms of hormone signaling used in multicellular organisms. Thus, the analysis of the pheromone signal pathway in yeast directly contributes to the study of cell growth and development in other eukaryotic organisms. PMID- 1444340 TI - Who's listening to whom? PMID- 1444341 TI - Hurricanes Andrew and Iniki are still with us. PMID- 1444342 TI - One solution for pressure sores. PMID- 1444343 TI - Surgical glove study questioned. PMID- 1444344 TI - Board approves formation of two Specialty Assemblies, proposed revisions to 'AORN Official Statement on RN First Assistant'. PMID- 1444345 TI - Project 2000. The difference between conceptual models, practice models. PMID- 1444346 TI - Solving the mystery of perioperative nursing. An OR Nurse Week program. PMID- 1444347 TI - The mentoring relationship. PMID- 1444348 TI - Covert actions by a coworker. Identification, consequences, solutions. AB - Saboteurs cannot survive if overt communication exists. Open lines of communication discourage unethical behavior and make it difficult for saboteurs to cause problems. Managers must learn to confront problems directly and then move on. Employees should be encouraged to practice direct, open communication and not to repeat rumors and gossip. Also, it is important to provide overt support for overt communication and behavior. Supporting directness is one way to discourage sabotage. Everyone involved needs to remember that it is easy to blame the messenger, but saboteurs cannot continue to practice deceit if others are not willing to listen to and encourage their continuous gossip. PMID- 1444349 TI - Workaholism. Learning self-care to prevent burnout. PMID- 1444350 TI - Argon beam coagulation. New directions in surgery. PMID- 1444351 TI - Compartment syndrome. A closer look at etiology, treatment. PMID- 1444352 TI - Anatomy of a lawsuit. PMID- 1444353 TI - Recommended practices. Skin preparation of patients. Association of Operating Room Nurses. PMID- 1444354 TI - Isolation of Trypanosoma cruzi from blood by histopaque and continuous percoll gradient centrifugations. AB - Separation of the blood forms of trypanosomes from the blood of infected animals is difficult, especially in the case of Trypanosoma cruzi Y strain. Two procedures to isolate the Y strain blood forms of T. cruzi using polyvinyl pyrrolidone-coated silica (percoll) and histopaque are reported in this study. The recovery rates of parasites were 16 +/- 5 and 68 +/- 16%, respectively. The parasites isolated by these methods presented normal motility and morphology and were infective to albino mice with prepatent periods, parasitemia curves, and polymorphism patterns during the infection that were similar to those of control parasites. In addition, the preservation of surface antigens was confirmed by immunocytochemical studies. PMID- 1444355 TI - Purification and general biochemical properties of thermostable pullulanase from Bacillus stearothermophilus G-82. AB - Thermostable extracellular pullulanase, produced by Bacillus stearothermophilus G 82 was purified to homogeneity from supernatants of continuous culture by ultrafiltration, ammonium sulphate precipitation, chromatography on Sephadex G 100, and DEAE cellulose. A mol wt of 53,000 was determined by gel filtration and 56,000 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The isoelectric point (pI) was 4.2. The pullulanase contained predominantly acidic amino acids. The enzyme was optimally active at a temperature of 60 degrees C and pH 7.0. It preserved 100% of its activity after 10 min treatment at 60 degrees C. The thermostability was considerably increased in the presence of pullulan. Ca2+ did not increase activity or thermostability. Enzyme activity was fully inhibited by N-bromosuccinimide and partially by phenylmethylsulfonyl fluoride. Bacillus stearothermophilus G-82 pullulanase was able to hydrolyze alpha 1-6 as well as alpha 1-4 glucosidic bonds in pullulan, amylopectin, amylose, glycogen, and dextrin. The enzyme showed highest affinity to pullulan (Km = 0.14). PMID- 1444356 TI - Immobilized triosephosphate isomerases. A comparative study. AB - Pig muscle triosephosphate isomerase was covalently attached to polyacrylamide and silica-based supports possessing carboxylic or aldehyde functional groups or activated with p-benzoquinone. A silica-based support activated with p benzoquinone proved to be the most advantageous. There were no profound alterations in the catalytic properties as a result of the immobilization. The immobilization enhanced the resistance against urea and heat treatment. At the start of the treatments, the enzyme was activated. The extent of activation depended on the pH, and on the buffer and salt concentrations. Increase of the ionic strength decreased or eliminated the activation. The phosphate ion had a specific effect on the thermal inactivation. PMID- 1444357 TI - A simple method for detection of monoclonal isotypes. AB - A simple rapid method of enzyme labeled anti-isotype assay (ELIA) for detection of monoclonal isotype on hybridoma cells is proposed. This alternative method was first carried out on hybridoma cell lines 147C11 and 257C11 produced against Trypanosoma cruzi and male accessory secretion of Panstrongylus megistus, respectively. The monoclonal antibodies produced by these hybridoma were characterized by this method as IgM (147C11) and IgG1 (257C23) isotypes, allowing evaluation of isotype without having to wait until the concentration of antibody present in the supernatant itself rises. Results were confirmed by Ouchterlony immunodiffusion. The proposed method offers the advantages of a permanent rapid procedure for light microscopy. PMID- 1444358 TI - Uptake of ammonia by Saccharomyces cerevisiae carrying the plasmid pCYG4 related with ammonia assimilation. AB - Batch culture experiments involving ammonia uptake in Saccharomyces cerevisiae BC55 pCYG4 have been carried out. This strain carries the plasmid pCYG4 that directs substantial overproduction of NADP-GDH, conferring an 11-fold increase in activity. The wild type cells had a specific growth rate greater than BC55 pCYG4. The ammonia uptake was practically the same until 15 h of growth. However, the amount of ammonia hydroxide added during growth (60 h) was two and half times greater in the BC55 pCYG4 than wild type cells. The results suggest that the presence of the plasmid pCYG4 can increase the amount of ammonia taken by the cells, but not the amount of biomass. PMID- 1444359 TI - Quantitation of E. coli protein impurities in recombinant human interferon-gamma. AB - A multiple antigen ELISA for E. coli proteins (ECPs) that may be present in purified recombinant human interferon-gamma (rIFN-gamma) was developed. SDS-PAGE and Western blotting analyses showed that the assay antibodies reacted with a wide spectrum of ECPs in the standard and with ECPs in a production run. In spike recovery studies, rIFN-gamma at concentrations of 0.05 mg/mL and higher augmented the immunoreactivity of the ECPs in the standard curve (1.3-40.0 ng ECPs/mL) by approx 50%. To determine ECP content in purified rIFN-gamma, 0.2 mg/mL of rIFN gamma was added to the standard curve diluent to compensate for enhanced immunoreactivity. The assay was precise (interassay precision of ECP controls < or = 4.1 %CV) and accurate with recoveries of 111-115% of expected for ECPs (15 40 ng/mL) spiked into purified rIFN-gamma (1 mg/mL). Linearity of dilution for ECPs spiked into rIFN-gamma was obtained (r = 0.999). Moreover, linearity of dilution was obtained for ECPs in "in-process" samples, demonstrating the required condition of antibody excess for this type of multiple antigen ELISA. ECPs were not detectable in several purified lots of rIFN-gamma. Therefore, these lots contained < 1.3 ppm ECPs. PMID- 1444360 TI - Fungal biodegradation of lignopolystyrene graft copolymers. AB - White rot basidiomycetes were able to biodegrade styrene (1-phenylethene) graft copolymers of lignin containing different proportions of lignin and polystyrene [poly(1-phenylethylene)]. The biodegradation tests were run on lignin-styrene copolymerization products which contained 10.3, 32.2, and 50.4% (wt/wt) lignin. The polymer samples were incubated with the white rot fungi Pleurotus ostreatus, Phanerochaete chrysosporium, and Trametes versicolor and the brown rot fungus Gloeophyllum trabeum. White rot fungi degraded the plastic samples at a rate which increased with increasing lignin content in the copolymer sample. Both polystyrene and lignin components of the copolymer were readily degraded. Polystyrene pellets were not degradable in these tests. Degradation was verified for both incubated and control samples by weight loss, quantitative UV spectrophotometric analysis of both lignin and styrene residues, scanning electron microscopy of the plastic surface, and the presence of enzymes active in degradation during incubation. Brown rot fungus did not affect any of the plastics. White rot fungi produced and secreted oxidative enzymes associated with lignin degradation in liquid media during incubation with lignin-polystyrene copolymer. PMID- 1444361 TI - Toxin production by Fusarium species from sugar beets and natural occurrence of zearalenone in beets and beet fibers. AB - Fifty-five Fusarium isolates belonging to nine species were collected from fungus invaded tissue of stored sugar beets and identified as F. acuminatum (11 isolates), F. avenaceum (1 isolate), F. culmorum (1 isolate), F. equiseti (23 isolates), F. graminearum (4 isolates), F. oxysporum (1 isolate), F. solani (4 isolates), F. sporotrichioides (7 isolates), and F. subglutinans (2 isolates). All isolates were cultured on autoclaved rice grains and assayed for toxicity by feeding weanling female rats the ground-rice cultures of the isolates in a 50% mixture with a regular diet for 5 days. Fifty-eight percent of the isolates were acutely toxic to rats, 26% caused hematuria, 18% caused hemorrhages, and 29% caused uterine enlargement. In most cases, toxicity could not be accounted for by the known toxins found. The following mycotoxins were found in extracts of the rice cultures: zearalenone (22 to 6,282 micrograms/g), chlamydosporol (HM-8) (68 to 4,708 micrograms/g), moniliformin (45 to 400 micrograms/g), deoxynivalenol (10 to 34 micrograms/g), 15-acetyldeoxynivalenol (5 to 10 micrograms/g), diacetoxyscirpenol (22 to 63 micrograms/g), monoacetoxyscirpenol (21 to 26 micrograms/g), scirpenetriol (24 micrograms/g), T-2 toxin (4 to 425 micrograms/g), HT-2 toxin (2 to 284 micrograms/g), neosolaniol (2 to 250 micrograms/g), and T-2 tetraol (4 to 12 micrograms/g). F. equiseti was the predominant species found on visibly molded beets in the field. Six of 25 moldy sugar beet root samples collected in the field contained zearalenone in concentrations ranging between 12 and 391 ng/g, whereas 10 samples from commercial stockpiles were negative for zearalenone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444362 TI - Seasonal incidence of Vibrio vulnificus in the Great Bay estuary of New Hampshire and Maine. AB - Vibrio vulnificus, a normal bacterial inhabitant of estuaries, is of concern because it can be a potent human pathogen, causing septicemia, wound infections, and gastrointestinal disease in susceptible hosts. From May 1989 through December 1990, oysters and/or water were obtained from six areas in the Great Bay estuary of New Hampshire and Maine. Water was also sampled from three freshwater sites that lead into these areas. V. vulnificus was first detected in the estuary in early July and remained present through September. V. vulnificus was isolated routinely during this period from oysters and water of the Squamscott, Piscataqua, and Oyster Rivers but was only isolated twice from the oysters or water of the Great Bay itself. This study determined that there was a strong correlation (by analysis of variance) between temperature, salinity, and the presence of V. vulnificus in water and oysters. However, other unidentified factors appear to influence its presence in certain areas of the estuary. PMID- 1444363 TI - Enhanced octadecane dispersion and biodegradation by a Pseudomonas rhamnolipid surfactant (biosurfactant). AB - A microbial surfactant (biosurfactant) was investigated for its potential to enhance bioavailability and, hence, the biodegradation of octadecane. The rhamnolipid biosurfactant used in this study was extracted from culture supernatants after growth of Pseudomonas aeruginosa ATCC 9027 in phosphate limited proteose peptone-glucose-ammonium salts medium. Dispersion of octadecane in aqueous solutions was dramatically enhanced by 300 mg of the rhamnolipid biosurfactant per liter, increasing by a factor of more than 4 orders of magnitude, from 0.009 to > 250 mg/liter. The relative enhancement of octadecane dispersion was much greater at low rhamnolipid concentrations than at high concentrations. Rhamnolipid-enhanced octadecane dispersion was found to be dependent on pH and shaking speed. Biodegradation experiments done with an initial octadecane concentration of 1,500 mg/liter showed that 20% of the octadecane was mineralized in 84 h in the presence of 300 mg of rhamnolipid per liter, compared with only 5% octadecane mineralization when no surfactant was present. These results indicate that rhamnolipids may have potential for facilitating the bioremediation of sites contaminated with hydrocarbons having limited water solubility. PMID- 1444364 TI - Purification and properties of 3-hydroxybutyryl-coenzyme A dehydrogenase from Clostridium beijerinckii ("Clostridium butylicum") NRRL B593. AB - The enzyme 3-hydroxybutyryl-coenzyme A (CoA) dehydrogenase has been purified 45 fold to apparent homogeneity from the solvent-producing anaerobe Clostridium beijerinckii NRRL B593. The identities of 34 of the N-terminal 35 amino acid residues have been determined. The enzyme exhibited a native M(r) of 213,000 and a subunit M(r) of 30,800. It is specific for the (S)-enantiomer of 3 hydroxybutyryl-CoA. Michaelis constants for NADH and acetoacetyl-CoA were 8.6 and 14 microM, respectively. The maximum velocity of the enzyme was 540 mumol min-1 mg-1 for the reduction of acetoacetyl-CoA with NADH. The enzyme could use either NAD(H) or NADP(H) as a cosubstrate; however, kcat/Km for the NADH-linked reaction was much higher than the apparent value for the NADPH-linked reaction. Also, NAD(H)-linked activity was less sensitive to changes in pH than NADP(H)-linked activity was. In the presence of 9.5 microM NADH, the enzyme was inhibited by acetoacetyl-CoA at concentrations as low as 20 microM, but the inhibition was relieved as the concentration of NADH was increased, suggesting a possible mechanism for modulating the energy efficiency during growth. PMID- 1444365 TI - Collapse of the proton motive force in Listeria monocytogenes caused by a bacteriocin produced by Pediococcus acidilactici. AB - The effect of pediocin JD, a bacteriocin produced by Pediococcus acidilactici JD1 23, on the proton motive force and proton permeability of resting whole cells of Listeria monocytogenes Scott A was determined. Control cells, treated with trypsin-inactivated bacteriocin at a pH of 5.3 to 6.1, maintained a pH gradient and a membrane potential of approximately 0.65 pH unit and 75 mV, respectively. However, these gradients were rapidly dissipated in cells after exposure to pediocin JD, even though no cell lysis had occurred. The pH gradient and membrane potential of the producer cells were also unaffected by the bacteriocin. Whole cells treated with bacteriocin were twice as permeable to protons as control cells were. The results suggest that the inhibitory action of pediocin JD against L. monocytogenes is directed at the cytoplasmic membrane and that inhibition of L. monocytogenes may be caused by the collapse of one or both of the individual components of the proton motive force. PMID- 1444366 TI - Phenotypic, antigenic, and molecular characterization of Pasteurella piscicida strains isolated from fish. AB - We compared Pasteurella piscicida strains isolated from different fish species in several European countries with strains isolated in Japan and the United States. The taxonomic analysis revealed that, regardless of the geographic origin and source of isolation, all the strains exhibited the same biochemical and physiological characteristics. Serological assays with different rabbit antisera demonstrated a high level of antigenic similarity among strains, with cross agglutination titers of 20,480 to 40,960. This serological homogeneity was supported by the lipopolysaccharide (LPS) and membrane protein profiles. All the P. piscicida strains had the same electrophoretic LPS pattern, showing O side chains with a ladder-like structure, and shared at least four major outer membrane proteins, of 20, 30, 42, and 53 kDa. Western blot (immunoblot) analysis with LPS and protein indicated that all the P. piscicida strains are immunologically related. In addition, the chromosomal DNA fingerprint patterns obtained for the European strains with the enzymes EcoRI and BamHI were practically identical to those of the Japanese and U.S. strains. Although some differences were found in the plasmid profiles of P. piscicida, a large number of strains possessed in common plasmid bands of 20 and 7 MDa. In addition, a plasmid of 50 MDa was present in the majority of the European strains. Restriction endonuclease analysis demonstrated the genetic homology of the plasmid bands shared by most of the European strains. All the P. piscicida strains had the same drug resistance patterns, indicating that a correlation between plasmid carriage and resistance to a specific antimicrobial agent cannot be established. The high levels of phenotypic, serological, and genetic homogeneity found among the P. piscicida strains should facilitate the development of DNA probes with diagnostic purposes as well as the design of effective vaccines. PMID- 1444367 TI - Evaluation of data transformations used with the square root and schoolfield models for predicting bacterial growth rate. AB - A comparison was made between mathematical variations of the square root and Schoolfield models for predicting growth rate as a function of temperature. The statistical consequences of square root and natural logarithm transformations of growth rate use in several variations of the Schoolfield and square root models were examined. Growth rate variances of Yersinia enterocolitica in brain heart infusion broth increased as a function of temperature. The ability of the two data transformations to correct for the heterogeneity of variance was evaluated. A natural logarithm transformation of growth rate was more effective than a square root transformation at correcting for the heterogeneity of variance. The square root model was more accurate than the Schoolfield model when both models used natural logarithm transformation. PMID- 1444368 TI - Evaluation of synergism among Bacillus thuringiensis toxins. AB - A simple test for synergism among toxins is described and applied to previously reported data on independent and joint toxicities of insecticidal proteins from Bacillus thuringiensis. The analysis shows synergism between a 27-kDa (CytA) toxin and 130- or 65-kDa (CryIV) toxins from B. thuringiensis subsp. israelensis against Aedes aegypti larvae. No positive synergism between 130- and 65-kDa toxins or among three CryIA toxins tested against seven species of Lepidoptera occurred. Comparisons with the original interpretations of these data show one case in which synergism occurred but was reported previously as absent and two cases that were not synergistic but were reported previously as suggestive of synergism. These results show that lack of an appropriate test for synergism can produce misleading conclusions. The methods described here can be used to test for synergistic effects of any poisons. PMID- 1444369 TI - Novel method to extract large amounts of bacteriocins from lactic acid bacteria. AB - Antimicrobial peptides, bacteriocins, produced by lactic acid bacteria were adsorbed on the cells of producing strains and other gram-positive bacteria. pH was a crucial factor in determining the degree of adsorption of these peptides onto cell surfaces. In general, between 93 and 100% of the bacteriocin molecules were adsorbed at pHs near 6.0, and the lowest (< or = 5%) adsorption took place at pH 1.5 to 2.0. On the basis of this property, a novel isolation method was developed for bacteriocins from four genera of lactic acid bacteria. By using this method we made preparations of pediocin AcH, nisin, sakacin A, and leuconocin Lcm1 that were potent and concentrated. This method produced a higher yield than isolation procedures, which rely on precipitation of the bacteriocins from the cell-free culture liquor. It is simple and can be used to produce large quantities of bacteriocins from lactic acid bacteria to be used as food biopreservatives. PMID- 1444370 TI - Expression and transfer of engineered catabolic pathways harbored by Pseudomonas spp. introduced into activated sludge microcosms. AB - Two genetically engineered microorganisms (GEMs), Pseudomonas sp. strain B13 FR1(pFRC20P) (FR120) and Pseudomonas putida KT2440(pWWO-EB62) (EB62), were introduced into activated sludge microcosms that had the level of aeration, nutrient makeup, and microbial community structure of activated sludge reactors. FR120 contains an experimentally assembled ortho cleavage route for simultaneous degradation of 3-chlorobenzoate (3CB) and 4-methyl benzoate (4MB); EB62 contains a derivative TOL plasmid-encoded degradative pathway for toluene experimentally evolved so that it additionally processes 4-ethyl benzoate (4EB). Experiments assessed survival of the GEMs, their ability to degrade target substrates, and lateral transfer of plasmid-encoded recombinant DNA. GEMs added at initial densities of 10(6) to 10(7) bacteria per ml of activated sludge declined to stable population densities of 10(4) to 10(5) bacteria per ml. FR120 degraded combinations of 3CB and 4MB (1 mM each) following 3 days of adaptation in the microcosms. Indigenous microorganisms required an 8-day adaptation period before degradation of 4MB was observed; 3CB was degraded only after the concentration of 4MB was much reduced. The indigenous microbial community was killed when both compounds were present at concentrations of 4.0 mM. However, in parallel microcosms containing FR120, the microbial community maintained a normal density of viable cells. Indigenous microbes readily degraded 4EB (2 mM), and EB62 did not significantly increase the observed rate of degradation. In filter matings, transfer of pFRC20P, which specifies mobilization but not transfer functions, from FR120 to P. putida UWC1 was not detectable (< 10(-7) transconjugants per donor cell).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444371 TI - Inhibition of alkylbenzene biodegradation under denitrifying conditions by using the acetylene block technique. AB - Addition of acetylene to microcosms simultaneously amended with nitrate and alkylbenzenes resulted in inhibition of the rate of alkylbenzene biodegradation under denitrifying conditions. Toluene, xylenes, and 1,2,4-trimethylbenzene were recalcitrant, whereas ethylbenzene was degraded at a slower rate than usual. Benzene was not degraded in either case. Addition of acetylene to microcosms preexposed to nitrate and alkylbenzenes produced similar inhibition. These data indicate that the activities of microorganisms that degrade alkylbenzenes under denitrifying conditions may be suppressed if the standard acetylene block technique is used to verify denitrifying activity. PMID- 1444372 TI - Cloning and expression of the aspartate carbamoyltransferase gene from Treponema denticola. AB - Treponema denticola seems to play a central role in the etiology of human periodontal disease. We have cloned an antigenic protein-coding sequence from T. denticola ATCC 33520. The protein-coding region was found to be a 3-kbp HindIII HindIII fragment. The open reading frame consists of 1,426 bp and codes for a protein with an M(r) of 54,919. The deduced amino acid sequence showed 33.8% homology with that of the aspartate carbamoyltransferase of Escherichia coli. The gene products showed aspartate carbamoyltransferase activity. PMID- 1444373 TI - Microbial transformation of benzocyclobutene to benzocyclobutene-1-ol and benzocyclobutene-1-one. AB - Oxidation of benzocyclobutene by intact cells of Pseudomonas fluorescens 127-68 XVII, containing naphthalene dioxygenase, yielded exclusively benzylic oxidation products; benzocyclobutene-1-ol and benzocyclobutene-1-one. No evidence for incorporation of oxygen into the aromatic ring was found. PMID- 1444374 TI - Stereospecific hydroxylation of indan by Escherichia coli containing the cloned toluene dioxygenase genes from Pseudomonas putida F1. AB - Escherichia coli JM109(pDTG601), containing the todC1C2BA genes encoding toluene dioxygenase from Pseudomonas putida F1, oxidizes indan to (-)-(1R)-indanol (83% R) and trans-1,3-indandiol. Under similar conditions, P. putida F39/D oxidizes indan to (-)-(1R)-indanol (96% R), 1-indanone, and trans-1,3-indandiol. The differences in the enantiomeric composition of the 1-indanols formed by the two organisms are due to the presence of a 1-indanol dehydrogenase in P. putida F39/D that preferentially oxidizes (+)-(1S)-indanol. PMID- 1444375 TI - Occurrence of tributyltin-tolerant bacteria in tributyltin- or cadmium-containing seawater. AB - Tributyltin chloride (TBTCl)-tolerant bacteria accounted for 90% of the flora in natural seawater to which TBTCl was added. These tolerant bacteria were insensitive to 250 nmol of TBTCl per disc, and all were Vibrio species. Total counts of viable bacteria did not decrease upon storage of the TBTCl-treated seawater, indicating that enrichment of tolerant strains took place. Addition of CdSO4 to seawater resulted in the occurrence of TBTCl-tolerant bacteria as well as Cd-tolerant bacteria, suggesting some correlation of Cd tolerance and TBTCl tolerance. PMID- 1444376 TI - Amplification of DNA from native populations of soil bacteria by using the polymerase chain reaction. AB - Specific DNA sequences from native bacterial populations present in soil, sediment, and sand samples were amplified by using the polymerase chain reaction with primers for either "universal" eubacterial 16S rRNA genes or mercury resistance (mer) genes. With standard amplification conditions, 1.5-kb rDNA fragments from all 12 samples examined and from as little as 5 micrograms of soil were reproducibly amplified. A 1-kb mer fragment from one soil sample was also amplified. The identity of these amplified fragments was confirmed by DNA-DNA hybridization. PMID- 1444377 TI - Use of an oligonucleotide probe to detect Vibrio parahaemolyticus in artificially contaminated oysters. AB - A 26-mer oligonucleotide specific to Vibrio parahaemolyticus was synthesized from a 1,275-bp thermostable direct hemolysin (tdh) gene. This oligonucleotide probe specifically reacted with DNA from 89 of 95 V. parahaemolyticus isolates but not with DNA from other vibrios or other enteric and nonenteric organisms (n = 48). The probe hybridized with Southern blots of 0.5-kb HindIII-restricted chromosomal DNA fragments from all but five V. parahaemolyticus test isolates. The probe could be used to directly identify V. parahaemolyticus in artificially contaminated food without an isolation step. PMID- 1444378 TI - Stabilization of botulinum toxin type A during lyophilization. AB - Botulinum toxin for medical use is diluted to very low concentrations (nanograms per milliliter); when it is preserved by lyophilization, considerable loss of activity can occur. In the present study, conditions that gave > 90% recovery of the toxicity after lyophilization of solutions containing 20 to 1,000 mouse 50% lethal doses per ml were found. Toxicity was recovered upon drying 0.1 ml of toxin solution when the pH was maintained below 7 and bovine or human serum albumins were used as stabilizers. Various other substances tested with albumin, including glucose, sucrose, trehalose, mannitol, glycine, and cellibiose, did not increase recovery on drying. PMID- 1444379 TI - Cloning of a creatinase gene from Pseudomonas putida in Escherichia coli by using an indicator plate. AB - A genomic library of Pseudomonas putida DNA was constructed by using plasmid pBR322. Transformants of Escherichia coli in combination with Proteus mirabilis cells grown on creatinase test plates were screened for creatinase activity; transformants were considered positive for creatinase activity if a red-pink zone appeared around the colonies. One creatinase-positive clone was further analyzed, and the gene was reduced to a 2.7-kb DNA fragment. A unique protein band (with a molecular weight of approximately 50,000) was observed in recombinant E. coli by minicell analysis. PMID- 1444380 TI - Detection and enumeration of bacteria in soil by direct DNA extraction and polymerase chain reaction. AB - In order to develop a rapid and specific detection test for bacteria in soil, we improved a method based on the polymerase chain reaction (PCR). Each step of the protocol, including direct lysis of cells, DNA purification, and PCR amplification, was optimized. To increase the efficiency of lysis, a step particularly critical for some microorganisms which resist classical techniques, we used small soil samples (100 mg) and various lytic treatments, including sonication, microwave heating, and thermal shocks. Purification of nucleic acids was achieved by passage through up to three Elutip d columns. Finally, PCR amplifications were optimized via biphasic protocols using booster conditions, lower denaturation temperatures, and addition of formamide. Two microorganisms were used as models: Agrobacterium tumefaciens, which is naturally absent from the soil used and was inoculated to calibrate the validity of the protocol, and Frankia spp., an actinomycete indigenous to the soil used. Specific primers were characterized either in the plasmid-borne vir genes for A. tumefaciens or in the variable regions of the 16S ribosomal gene for Frankia spp. Specific detection of the inoculated A. tumefaciens strain was routinely obtained when inocula ranged from 10(7) to 10(3) cells. Moreover, the strong correlation we observed between the size of the inocula and the results of the PCR reactions permitted assessment of the validity of the protocol in enumerating the number of microbial cells present in a soil sample. This allowed us to estimate the indigenous population of Frankia spp. at 0.2 x 10(5) genomes (i.e., amplifiable target sequences) per g of soil. PMID- 1444381 TI - Physiological properties of a Pseudomonas strain which grows with p-xylene in a two-phase (organic-aqueous) medium. AB - Pseudomonas putida Idaho utilizes toluene, m-xylene, p-xylene, 1,2,4 trimethylbenzene, and 3-ethyltoluene as growth substrates when these hydrocarbons are provided in a two-phase system at 5 to 50% (vol/vol). Growth also occurs on Luria-Bertani medium in the presence of a wide range of organic solvents. The ability of the organism to grow in the presence of organic solvents is correlated with the logarithm of the octanol-water partition coefficient, with dimethyl phthalate (log P(OCT) = 2.3) being the most polar solvent tolerated. During growth with p-xylene (20% [vol/vol]), there was an initial lag period accompanied by cell death, which was followed by a period of exponential growth. The stationary phase of growth was characterized by a dramatic decrease in cell viability, although cell dry weight and turbidity measurements slowly increased. Electron micrographs revealed that during growth in the presence of p-xylene, the outer cell membrane becomes convoluted and membrane fragments are shed into the culture medium. At the same time, the cytoplasmic membrane invaginates, forming vesicles, and becomes disorganized. Electron-dense intracellular inclusions were observed in cells grown with p-xylene (20% [vol/vol]) and p-xylene vapors, which are not present in cells grown with succinate. Attempts to demonstrate the presence of plasmid DNA in P. putida Idaho were negative. However, polarographic studies indicated that the organism utilizes the same pathway for the degradation of toluene, m-xylene, and p-xylene as that used by P. putida mt-2 which contains the TOL plasmid pWWO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444382 TI - Metabolism of toxic pyrrolizidine alkaloids from tansy ragwort (Senecio jacobaea) in ovine ruminal fluid under anaerobic conditions. AB - The ability of ovine ruminal fluid to metabolize pyrrolizidine alkaloid (PA) from Senecio jacobaea under anaerobic conditions was evaluated. Four fistulated sheep fed PA served as individual sources of ruminal fluid, which was incubated in a defined minimal salts medium under two different anaerobic conditions, denitrifying and methanogenic. Anaerobic cultures amended with ovine ruminal fluids (20%), PA (100 micrograms/ml), and a defined minimal salts medium were monitored for a period of several days. These cultures revealed that while PA was not depleted in sterile, autoclaved controls or under denitrifying conditions, it was metabolized during periods of active methanogenesis under methanogenic conditions. In addition, samples of ruminal fluid were separated by differential centrifugation under anaerobic conditions, and the resultant supernatants were tested for their ability to metabolize PA as compared with those of the respective uncentrifuged control fluids. Uncentrifuged controls exhibited a PA depletion rate of -4.04 +/- 0.17 micrograms of PA per ml per h. Supernatants 1 (centrifuged at 41 x g for 2 min), 2 (centrifuged at 166 x g for 5 min), and 3 (centrifuged at 1,500 x g for 10 min) exhibited significantly slower depletion rates, with slopes of data representing -1.64 +/- 0.16, -1.44 +/- 0.16, and -1.48 +/- 0.16 micrograms of PA metabolized per ml per h, respectively, demonstrating no statistically significant difference among the supernatant cultures. Microscopic evaluations revealed that protozoa were present in the control whole ruminal fluid and to a lesser extent in supernatant 1, while supernatants 2 and 3 contained only bacteria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444383 TI - Hydrodynamic effects on microcapillary motility and chemotaxis assays of Methylosinus trichosporium OB3b. AB - A study of the random motility and chemotaxis of Methylosinus trichosporium OB3b was conducted by using Palleroni-chamber microcapillary assay procedures. Under the growth conditions employed, this methanotroph was observed qualitatively with a microscope to be either slightly motile or essentially nonmotile. However, the cells did not not respond in the microcapillary assays in the manner expected for nonmotile Brownian particles. As a consequence, several hydrodynamic effects on these Palleroni microcapillary assays were uncovered. In the random-motility microcapillary assay, nondiffusive cell accumulations occurred that were strongly dependent upon cell concentration. An apparent minimal random-motility coefficient (mu) for this bacterial cell of 1.0 x 10(-7) cm2/s was estimated from microcapillary assays. A simple alternative spectrophotometric assay, based upon gravitational settling, was developed and shown to be an improvement over the Palleroni microcapillary motility assay for M. trichosporium OB3b in that it yielded a more-accurate threefold-lower random-motility coefficient. In addition, it provided a calculation of the gravitational-settling velocity. In the chemotaxis microcapillary assay, the apparent chemotactic responses were strongest for the highest test-chemical concentrations in the microcapillaries, were correlated with microcapillary fluid density, and were strongly dependent upon the microcapillary volume. A simple method to establish the maximal concentration of a chemical that can be tested and to quantify any contributions of abiotic convection is described. Investigators should be aware of the potential problems due to density-driven convection when using these commonly employed microcapillary assays for studying cells which have low motilities. PMID- 1444384 TI - Biodegradation of diphenyl ether and its monohalogenated derivatives by Sphingomonas sp. strain SS3. AB - The bacterium Sphingomonas sp. strain SS3, which utilizes diphenyl ether and its 4-fluoro, 4-chloro, and (to a considerably lesser extent) 4-bromo derivatives as sole sources of carbon and energy, was enriched from soil samples of an industrial waste deposit. The bacterium showed cometabolic activities toward all other isomeric monohalogenated diphenyl ethers. During diphenyl ether degradation in batch culture experiments, phenol and catechol were produced as intermediates which were then channeled into the 3-oxoadipate pathway. The initial step in the degradation follows the recently discovered mechanism of 1,2-dioxygenation, which yields unstable phenolic hemiacetals from diphenyl ether structures. Oxidation of the structure-related dibenzo-p-dioxin yielded 2-(2-hydroxyphenoxy)-muconate upon ortho cleavage of the intermediate 2,2',3-trihydroxydiphenyl ether. Formation of phenol, catechol, halophenol, and halocatechol from the conversion of monohalogenated diphenyl ethers gives evidence for a nonspecific attack of the dioxygenating enzyme system. PMID- 1444385 TI - Genetic analysis of a locus on the Bacteroides ovatus chromosome which contains xylan utilization genes. AB - Bacteroides ovatus, a gram-negative obligate anaerobe found in the human colon, can utilize xylan as a sole source of carbohydrate. Previously, a 3.8-kbp segment of B. ovatus chromosomal DNA, which contained genes encoding a xylanase (xylI) and a bifunctional xylosidase-arabinosidase (xsa), was cloned, and expression of the two genes was studied in Escherichia coli (T. Whitehead and R. Hespell, J. Bacteriol. 172:2408-2412, 1990). In the present study, we have used segments of the cloned region to construct insertional disruptions in the B. ovatus chromosomal locus containing these two genes. Analysis of these insertional mutants demonstrated that (i) xylI and xsa are probably part of the same operon, with xylI upstream of xsa, (ii) the true B. ovatus promoter was not cloned on the 3.5-kbp DNA fragment which expressed xylanase and xylosidase in E. coli, (iii) there is at least one gene upstream of xylI which could encode an arabinosidase, and (iv) xylosidase rather than xylanase may be a rate-limiting step in xylan utilization. Insertional mutations in the xylI-xsa locus reduced the rate of growth on xylan, but the concentration of residual sugars at the end of growth was the same as that with the wild type. Thus, a slower rate of growth on xylan was not accompanied by less extensive digestion of xylan. Mutants in which xylI had been disrupted still expressed some xylanase activity. This second activity was associated with membranes and produced xylose from xylan, whereas the xylI gene product partitioned primarily with the soluble fraction and produced xylobiose from xylan. PMID- 1444386 TI - Virulence characteristics of clinical and environmental isolates of Vibrio vulnificus. AB - Twenty-four randomly selected clinical and environmental Vibrio vulnificus isolates were tested for virulence in iron-overloaded mice (250 mg of iron dextran per kg of body weight). The log10 50% lethal doses of 17 isolates were lower by greater than or equal to 3.5 log10 units in iron-overloaded mice than in control mice. These isolates were classified as virulent. The 50% lethal doses of these virulent isolates were also lower in mice that were immunosuppressed by treatment with cyclophosphamide (150 mg/kg). Four of the seven isolates initially classified as avirulent were virulent in mice that were simultaneously iron overloaded and immunosuppressed. These isolates were classified as moderately virulent. The remaining three isolates were avirulent under all conditions. The incidence of virulent strains among clinical and environmental isolates did not differ. The virulent isolates produced high titers of hemolysin, were resistant to inactivation by serum complement, produced phenolate siderophore, and utilized transferrin-bound iron. The moderately virulent isolates differed from the virulent isolates only in their increased sensitivity to inactivation by serum complement. The avirulent isolates differed from those of the other two classes in their inability to either produce significant amounts of phenolate siderophore or utilize transferrin-bound iron. A modified agar plate diffusion method for transferrin-bound iron utilization was developed to differentiate the two classes of virulent isolates from the avirulent isolates in vitro. PMID- 1444387 TI - A model study of factors involved in adhesion of Pseudomonas fluorescens to meat. AB - A study was undertaken to investigate the factors involved in the adhesion of Pseudomonas fluorescens to model meat surfaces (tendon slices). Adhesion was fast (less than 2.5 min) and was not suppressed by killing the cells with UV, gamma rays, or heat, indicating that physiological activity was not required. In various salt solutions (NaCl, KCl, CaCl2, MgCl2), adhesion increased with increasing ionic strength up to 10 to 100 mM, suggesting that, at low ionic strengths, electrostatic interactions were involved in the adhesion process. At higher ionic strengths (greater than 10 to 100 mM) or in the presence of Al3+ ions, adhesion was sharply reduced. Selectively blocking of carboxyl or amino groups at the cell surface by chemical means did not affect adhesion. These groups are therefore not directly involved in an adhesive bond with tendon. Given a sufficient cell concentration (10(10) CFU.ml-1) in the adhesion medium, the surface of tendon was almost entirely covered with adherent bacteria. This suggests that if the adhesion is specific, the attachment sites on the tendon surface must be located within collagen or proteoglycan molecules. PMID- 1444388 TI - Loss of allosteric control but retention of the bifunctional catalytic competence of a fusion protein formed by excision of 260 base pairs from the 3' terminus of pheA from Erwinia herbicola. AB - A bifunctional protein denoted as the P protein and encoded by pheA is widely present in purple gram-negative bacteria. This P protein carries catalytic domains that specify chorismate mutase (CM-P) and prephenate dehydratase. The instability of a recombinant plasmid carrying a pheA insert cloned from Erwinia herbicola resulted in a loss of 260 bp plus the TAA stop codon from the 3' terminus of pheA. The plasmid carrying the truncated pheA gene (denoted pheA*) was able to complement an Escherichia coli pheA auxotroph. pheA* was shown to be a chimera composed of the residual 5' part of pheA (901 bp) and a 5-bp fragment from the pUC18 vector. The new fusion protein (PheA*) retained both chorismate mutase and prephenate dehydratase activities. PheA* had a calculated subunit molecular weight of 33,574, in comparison to the 43,182-molecular-weight subunit size of PheA. The deletion did not affect the ability of PheA* to assume the native dimeric configuration of PheA. Both the CM-P and prephenate dehydratase components of PheA* were insensitive to L-phenylalanine inhibition, in contrast to the corresponding components of PheA. L-Phenylalanine protected both catalytic activities of PheA from thermal inactivation, and this protective effect of L phenylalanine upon the PheA* activities was lost. PheA* was more stable than PheA to thermal inactivation; this was more pronounced for prephenate dehydratase than for CM-P. In the presence of dithiothreitol, the differential resistance of PheA* prephenate dehydratase to thermal inactivation was particularly striking.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444389 TI - Heritability of fumonisin B1 production in Gibberella fujikuroi mating population A. AB - Fumonisins are mycotoxins produced by strains belonging to several different mating populations of Gibberella fujikuroi (anamorphs, Fusarium section Liseola), a major pathogen of maize and sorghum worldwide. We studied the heritability of fumonisin production in mating population A by crossing fumonisin-producing strains collected from maize and sorghum in the United States with fumonisin nonproducing strains collected from maize in Nepal. Random ascospore and tetrad progeny from three of these crosses were analyzed by gas chromatography-mass spectrometry and high-performance liquid chromatography for their ability to produce fumonisins on autoclaved cracked maize. In all three crosses, the ability to produce fumonisins, predominately fumonisin B1, segregated as a single gene or group of closely linked genes. Intercrosses between appropriate progeny and parents were poorly fertile, so we could not determine if the apparent single genes that were segregating in each of these crosses were allelic with one another. Mating type and spore-killer traits were scored in some crosses, and each segregated, as expected, as a single gene that was unlinked to the ability to produce fumonisins. We conclude that G. fujikuroi mating population A provides a powerful genetic system for the study of this important fungal toxin. PMID- 1444390 TI - Cloning and nucleotide sequence of the gene coding for aspartokinase II from a thermophilic methylotrophic Bacillus sp. AB - The structural gene coding for the lysine-sensitive aspartokinase II of the methylotrophic thermotolerant Bacillus sp. strain MGA3 was cloned from a genomic library by complementation of an Escherichia coli auxotrophic mutant lacking all three aspartokinase isozymes. The nucleotide sequence of the entire 2.2-kb PstI fragment was determined, and a single open reading frame coding for the aspartokinase II enzyme was found. Aspartokinase II was shown to be an alpha 2 beta 2 tetramer (M(r) 122,000) with the beta subunit (M(r) 18,000) encoded within the alpha subunit (M(r) 45,000) in the samea reading frame. The enzyme was purified, and the N-terminal sequences of the alpha and beta subunits were identical with those predicted from the gene sequences. The predicted amino acid sequence was 76% identical with the sequence of the Bacillus subtilis aspartokinase II. The transcription initiation site was located approximately 350 bp upstream of the translation start site, and putative promoter regions at -10 (TATGCT) and -35 (ATGACA) were identified. A 300-nucleotide intervening sequence between the transcription initiation and translational start sites suggests a possible attenuation mechanism for the regulation of transcription of this enzyme in the presence of lysine. PMID- 1444391 TI - Quantitative spectrophotometric assay for staphylococcal lipase. AB - We report the development of a specific spectrophotometric assay for the quantitative determination of lipase activity in Staphylococcus aureus. The assay is based on the rate of clearance of a tributyrin emulsion, and it can detect as little as 1.0 micrograms of purified Pseudomonas lipase per ml. By comparison with the reaction rates obtained with Pseudomonas lipase, we calculated that S. aureus PS54C and S6C produce approximately 15 and 60 micrograms of extracellular lipase per ml, respectively. Neither PS54, which is lysogenized with the converting bacteriophage L54a and is consequently lipase negative (Lip-), nor KS1905, a Lip- transpositional mutant of strain S6C, was positive in our spectrophotometric assay. The specificity of the spectrophotometric tributyrin assay was confirmed with a triolein plate assay; supernatants from S6C and PS54C hydrolyzed triolein, while supernatants from PS54 and KSI905 did not. In contrast to the results of the spectrophotometric tributyrin assay, all enzyme preparations tested (including commercially purified esterase) were positive when examined by a tributyrin plate assay. The lack of specificity in the tributyrin plate assay emphasizes the need to interpret the results of tributyrin lipolysis kinetically for assessing lipase activity in S. aureus. PMID- 1444392 TI - Immunological demonstration of a unique 3,4-dihydroxyphenylacetate 2,3 dioxygenase in soil Arthrobacter strains. AB - Many bacteria biosynthesize 3,4-dihydroxyphenylacetate 2,3-dioxygenases for growth on aromatic acids, but gram-negative organisms have been most extensively studied. A gram-positive strain containing 2,3-dioxygenase activity was identified as Arthrobacter strain Mn-1. The 2,3-dioxygenase from strain Mn-1 was purified to homogeneity by fast protein liquid chromatography with a Mono Q anion exchange column. Rabbit polyclonal antidioxygenase antibodies were prepared. Ouchterlony double-diffusion and Western blotting (immunoblotting) protocols were used to probe the distribution of the Mn-1 dioxygenase antigen in soil bacteria. Fourteen 2,3-dioxygenase-containing Bacillus and Pseudomonas strains did not contain immunologically cross-reactive proteins. Six of eight Arthrobacter strains contained 2,3-dioxygenase activity, and all of them produced cross reactive proteins. The data presented here suggest that a unique type of dioxygenase is geographically widespread but is taxonomically confined to Arthrobacter soil bacteria. PMID- 1444393 TI - 16S rRNA-based probes and polymerase chain reaction method to detect Listeria monocytogenes cells added to foods. AB - A rapid polymerase chain reaction (PCR) method was developed for detection of Listeria monocytogenes in foods. This method used a pair of primers based on a unique region in the 16S rRNA sequence of L. monocytogenes, which were previously reported by us to yield a specific nucleic acid probe. Our method included use of a shorter denaturing time, a shorter annealing time, a rapid transition, and an increase in the number of cycles, resulting in good sensitivity. Just 3 h for PCR plus 1 h for electrophoresis was required. Additional time for DNA isolation and DNA hybridization was not needed. This method detected as few as 2 to 20 CFU of L. monocytogenes in pure cultures and as few as 4 to 40 CFU of L. monocytogenes in inoculated (10(8) CFU), diluted food samples. Seven of eight foods, including four poultry products, gave positive results. Only one food sample, soft cheese, gave interference. An internal probe hybridization test was used to confirm that the PCR products were from L. monocytogenes. A specificity test indicated that this PCR method was positive for all 13 strains of L. monocytogenes tested but negative for the other 6 species of Listeria, including 6 strains of L. innocua, and negative for 17 other gram-positive and gram-negative bacteria tested. PMID- 1444394 TI - Genetic relatedness of Bradyrhizobium japonicum field isolates as revealed by repeated sequences and various other characteristics. AB - Forty-nine isolates of Bradyrhizobium japonicum indigenous to a field where soybeans were grown for 45 years without inoculation were characterized by using four DNA hybridization probes from B. japonicum. nifDK-specific hybridization clearly divided the isolates into two divergent groups. Diversity in repeated sequence (RS)-specific hybridization was observed; 44 isolates derived from 41 nodules were divided into 33 different RS fingerprint groups. Cluster analysis showed that the RS fingerprints were correlated with the nif and hup genotypes. We found multiple bands of RS-specific hybridization for two isolates that differed from the patterns of the other isolates. These results suggest that RS fingerprinting is a valuable tool for evaluating the genetic structure of indigenous B. japonicum populations. PMID- 1444395 TI - Effects of Beauveria bassiana on embryos of the inland silverside fish (Menidia beryllina). AB - A chemical toxicity and teratogenicity test was adapted to assess potential adverse effects of a microbial pest control agent on a nontarget fish. Developing embryos of the inland silverside, Menidia beryllina, were exposed to conidiospores of the insect-pathogenic fungus Beauveria bassiana. Embryo rupture and death were observed. Embryo rupture did not always result in death, nor was death always associated with embryo rupture. Adherence of spores to the chorion, followed by germination and penetration by the germ tube, probably caused the embryos to rupture. Statistically significant (P less than or equal to 0.05) responses were observed in tests in which conidiospore concentrations were greater than or equal to 8.3 x 10(4) or less than or equal to 1.5 x 10(6)/ml. Conidiospores treated with a dispersant (biological detergent) showed significantly less binding (P less than or equal to 0.01) to embryos than did untreated spores. Both detergent-treated and heat-killed spores failed to cause significant adverse effects. PMID- 1444396 TI - Heat and cold shock protein synthesis in arctic and temperate strains of rhizobia. AB - We compared heat shock proteins (HSPs) and cold shock proteins (CSPs) produced by different species of Rhizobium having different growth temperature ranges. Several HSPs and CSPs were induced when cells of three arctic (psychrotrophic) and three temperate (mesophilic) strains of rhizobia were shifted from their optimal growth temperatures (arctic, 25 degrees C; temperate, 30 degrees C) to shock temperatures outside their growth temperature ranges. At heat shock temperatures, three major HSPs of high molecular weight (106,900, 83,100, and 59,500) were present in all strains for all shock treatments (29, 32, 36.4, 38.4, 40.7, 41.4, and 46.4 degrees C), with the exception of temperate strains exposed to 46.4 degrees C, in which no protein synthesis was detected. Cell survival of arctic and temperate strains decreased markedly with the increase of shock temperature and was only 1% at 46.4 degrees C. Under cold shock conditions, five proteins (52.0, 38.0, 23.4, 22.7, and 11.1 kDa) were always present for all treatments (-2, -5, and -10 degrees C) in arctic strains. Among temperate strains, five CSPs (56.1, 37.1, 34.4, 17.3, and 11.1 kDa) were present at temperatures down to 0 degrees C. The 34.4- and the 11.1-kDa components were present in all temperate strains at -5 degrees C and in one strain at -10 degrees C. Survival of all strains decreased with cold shock temperatures but was always higher than 50%. These results show that rhizobia can synthesize proteins at temperatures not permissive for growth. In all shock treatments, no correspondence between the number of HSPs or CSPs produced and rhizobial survival was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444397 TI - Screening for microorganisms producing D-malate from maleate. AB - More than 300 microorganisms were screened for their ability to convert maleate into D-malate as a result of the action of maleate hydratase. Accumulation of fumarate during incubation of permeabilized cells with maleate was shown to be indicative of one of the two enzymes known to transform maleate. The ratio in which fumarate and malate accumulated could be used to estimate the enantiomeric composition of the malate formed. Many strains (n = 128) were found to be capable of converting maleate to D-malate with an enantiomeric purity of more than 97%. Pseudomonas pseudoalcaligenes NCIMB 9867 was selected for more detailed studies. Although this strain was not able to grow on maleate, permeabilized cells were able to degrade maleate to undetectable levels, with a concomitant formation of D malate. The D-malate was formed with an enantiomeric purity of more than 99.97%. PMID- 1444398 TI - Induction of melanin biosynthesis in Vibrio cholerae. AB - Vibrio cholerae synthesized the pigment melanin in response to specific physiological conditions that were stressful to the bacterium. Pigmentation was induced when V. cholerae was subjected to hyperosmotic stress in conjunction with elevated growth temperatures (above 30 degrees C). The salt concentration tolerated by V. cholerae was lowered by additional abiotic factors such as acidic starting pH of the growth medium and limitation of organic nutrients. Although the amount of toxin detected in the culture supernatant decreased significantly in response to stressful culture conditions, no correlation between the physiological conditions that induced melanogenesis and expression of OmpU or cholera toxin was detected. Since conditions that induce melanin production in V. cholerae occur in both the aquatic environment and the human host, it is possible that melanogenesis has a specific function with respect to the survival of the bacterium in these habitats. PMID- 1444399 TI - Formation of poly(hydroxybutyrate-co-hydroxyvalerate) by Azotobacter vinelandii UWD. AB - Azotobacter vinelandii UWD formed polyhydroxyalkanoate (PHA) copolymers containing beta-hydroxybutyrate and beta-hydroxyvalerate (HV) when grown in a medium containing glucose as the primary C source and valerate (pentanoate) as a precursor. Copolymer was not formed when propionate was added to the glucose medium but was formed when heptanoate, nonanoate, or trans-2-pentenoate was present. Optimal levels of HV were formed when valerate was added at the time of maximum PHA synthesis, although HV incorporation was not dependent on glucose catabolism. HV content in the polymer was increased from 17 to 24 mol% by adding 10 to 40 mM valerate to glucose medium, but HV insertion into the polymer occurred at a fixed rate. Similarly, the addition of valerate to a fed-batch culture of strain UWD in beet molasses in a fermentor produced 19 to 22 g of polymer per liter, containing 8.5 to 23 mol% HV after 38 to 40 h. The synthesis of HV in these cultures also occurred at a fixed rate (2.3 to 2.8 mol% h-1), while the maximum PHA production rate was 1.1 g liter-1 h-1. During synthesis of copolymer in batch or fed-batch culture, the yield from conversion of glucose into PHA (YP/S) remained at maximum theoretical efficiency (greater than or equal to 0.33 g of PHA per g of glucose consumed). Up to 45 mol% C source, but the PHA produced amounted to less than 1 g/liter. The combination of 30 mM valerate as a sole C source and 0.5 mM 4-pentenoate increased the HV content in the polymer to 52 mol%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444400 TI - Isolation and characterization of an anaerobic chlorophenol-transforming bacterium. AB - An obligately anaerobic bacterium which transforms several chlorinated phenols was isolated. Dechlorination of the substituents ortho to the phenolic OH group was preferred, while removal of a meta-substituted chlorine was observed only with 3,5-dichlorophenol. The bacterium was a gram-positive, endospore-forming, motile, slightly curved rod. Sulfate was not reduced. Nitrate was reduced via nitrite to ammonium. The bacterium is related to the genus Clostridium. The highest growth rate was obtained in a medium containing pyruvate and yeast extract. Pyruvate supported growth as the sole source of carbon, and the fermentation of pyruvate produced almost equimolar amounts of acetate. PMID- 1444401 TI - Characterization of a novel Pseudomonas sp. that mineralizes high concentrations of pentachlorophenol. AB - A pentachlorophenol (PCP)-mineralizing bacterium was isolated from polluted soil and identified as Pseudomonas sp. strain RA2. In batch cultures, Pseudomonas sp. strain RA2 used PCP as its sole source of carbon and energy and was capable of completely degrading this compound as indicated by radiotracer studies, stoichiometric release of chloride, and biomass formation. Pseudomonas sp. strain RA2 was able to mineralize a higher concentration of PCP (160 mg liter-1) than any previously reported PCP-degrading pseudomonad. At a PCP concentration of 200 mg liter-1, cell growth was completely inhibited and PCP was not degraded, although an active population of Pseudomonas sp. RA2 was still present in these cultures after 2 weeks. The inhibitory effect of PCP was partially attributable to its effect on the growth rate of Pseudomonas sp. strain RA2. The highest specific growth rate (mu = 0.09 h-1) was reached at a PCP concentration of 40 mg liter-1 but decreased at higher or lower PCP concentrations, with the lowest mu (0.05 h-1) occurring at 150 mg liter-1. Despite this reduction in growth rate, total biomass production was proportional to PCP concentration at all PCP concentrations degraded by Pseudomonas sp. RA2. In contrast, final cell density was reduced to below expected values at PCP concentrations greater than 100 mg liter-1. These results indicate that, in addition to its effect as an uncoupler of oxidative phosphorylation, PCP may also inhibit cell division in Pseudomonas sp. strain RA2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444402 TI - Metal regulation of siderophore synthesis in Pseudomonas aeruginosa and functional effects of siderophore-metal complexes. AB - Pseudomonas aeruginosa synthesizes two siderophores, pyochelin and pyoverdin, characterized by widely different structures, physicochemical properties, and affinities for Fe(III). Titration experiments showed that pyochelin, which is endowed with a relatively low affinity for Fe(III), binds other transition metals, such as Cu(II), Co(II), Mo(VI), and Ni(II), with appreciable affinity. In line with these observations, Fe(III) and Co(II) at 10 microM or Mo(VI), Ni(II), and Cu(II) at 100 microM repressed pyochelin synthesis and reduced expression of iron-regulated outer membrane proteins of 75, 68, and 14 kDa. In contrast, pyoverdin synthesis and expression of the 80-kDa receptor protein were affected only by Fe(III). All of the metals tested, except Mo(VI), significantly promoted P. aeruginosa growth in metal-poor medium; Mo(VI), Ni(II), and Co(II) were more efficient as pyochelin complexes than the free metal ions and the siderophore. The observed correlation between the affinity of pyochelin for Fe(III), Co(II), and Mo(VI) and the functional effects of these metals indicates that pyochelin may play a role in their delivery to P. aeruginosa. PMID- 1444403 TI - Formation of unilamellar liposomes from total polar lipid extracts of methanogens. AB - Unilamellar liposomes were formed by controlled detergent dialysis of mixed micelles consisting of acetone-insoluble total polar lipids extracted from various methanogens and the detergent n-octyl-beta-D-glucopyranoside. The final liposome populations were studied by dynamic light scattering and electron microscopy. Unilamellar liposomes with mean diameters smaller than 100 nm were obtained with lipid extracts of Methanococcus voltae, Methanosarcina mazei, Methanosaeta concilii, and Methanococcus jannaschii (grown at 50 degrees C), whereas larger (greater than 100-nm) unilamellar liposomes were obtained with lipid extracts of M. jannaschii grown at 65 degrees C. These liposomes were shown to be closed intact vesicles capable of retaining entrapped [14C]sucrose for extended periods of time. With the exception of Methanospirillum hungatei liposomes, all size distributions of the different liposome populations were fairly homogeneous. PMID- 1444404 TI - Dynamic mathematical model to predict microbial growth and inactivation during food processing. AB - Many sigmoidal functions to describe a bacterial growth curve as an explicit function of time have been reported in the literature. Furthermore, several expressions have been proposed to model the influence of temperature on the main characteristics of this growth curve: maximum specific growth rate, lag time, and asymptotic level. However, as the predictive value of such explicit models is most often guaranteed only at a constant temperature within the temperature range of microbial growth, they are less appropriate in optimization studies of a whole production and distribution chain. In this paper a dynamic mathematical model--a first-order differential equation--has been derived, describing the bacterial population as a function of both time and temperature. Furthermore, the inactivation of the population at temperatures above the maximum temperature for growth has been incorporated. In the special case of a constant temperature, the solution coincides exactly with the corresponding Gompertz model, which has been validated in several recent reports. However, the main advantage of this dynamic model is its ability to deal with time-varying temperatures, over the whole temperature range of growth and inactivation. As such, it is an essential building block in (time-saving) simulation studies to design, e.g., optimal temperature-time profiles with respect to microbial safety of a production and distribution chain of chilled foods. PMID- 1444405 TI - Isolation and characterization of a fluorene-degrading bacterium: identification of ring oxidation and ring fission products. AB - An Arthrobacter sp. strain, F101, able to use fluorene as the sole source of carbon and energy, was isolated from sludge from an oil refinery wastewater treatment plant. During growth in the presence of fluorene, four major metabolites were detected and isolated by thin-layer chromatography and high performance liquid chromatography. 9-Fluorenol, 9H-fluoren-9-one, and 3,4 dihydrocoumarin were identified by UV spectra, mass spectrometry, and 300-MHz proton nuclear magnetic resonance. The fourth metabolite has been characterized, but precise identification was not possible. Since strain F101 is not able to grow with fluorenone, two different pathways of fluorene biodegradation are suggested: one supports cell growth and produces 3,4-dihydrocoumarin as an intermediate and probably the unidentified metabolite, and the other produces 9 fluorenol and 9H-fluoren-9-one and appears to be a dead-end route. PMID- 1444406 TI - Physiological studies of chloramine resistance developed by Klebsiella pneumoniae under low-nutrient growth conditions. AB - This study investigated the physiological mechanisms of resistance to chloramines developed by Klebsiella pneumoniae grown in a nutrient-limited environment. Growth under these conditions resulted in cells that were smaller than cells grown under high-nutrient conditions and extensively aggregated. Cellular aggregates ranged from 10 to more than 10,000 cells per aggregate, with a mean population aggregate size of 90 cells. This aggregation may have been facilitated by the presence of extracellular polymer material. By using glucose as a reference of capsule content, it was determined that growth under low-nutrient conditions produced cells with 8 x 10(-14) to 41 x 10(-14) g of carbohydrate per cell, with a mean +/- standard deviation of 27 x 10(-14) +/- 16 x 10(-14) g of carbohydrate per cell. In comparison, growth under high-nutrient conditions resulted in 2.7 x 10(-14) to 5.9 x 10(-14) g of carbohydrate per cell, with a mean and standard deviation of 4.3 x 10(-14) +/- 1.2 x 10(-14) g of carbohydrate per cell. Cell wall and cell membrane lipids also varied with growth conditions. The ratio of saturated to unsaturated fatty acids in cells grown under low nutrient conditions was approximately five times greater than that in cells grown under high-nutrient conditions, suggesting possible differences in membrane permeability. An analysis of sulfhydryl (-SH) groups revealed no quantitative difference with respect to growth conditions. However, upon exposure to chloramines, only 33% of the -SH groups of cells grown under low-nutrient conditions were oxidized, compared with 80% oxidization of -SH groups in cells grown under high-nutrient conditions. The reduced effectiveness of chloramine oxidization of -SH groups in cells grown under low-nutrient conditions may be due to restricted penetration of chloramines into the cells, conformational changes of enzymes, or a combination of both factors. The results of this study suggest that chloramine resistance developed under low-nutrient growth conditions may be a function of multiple physiological factors, including cellular aggregation and protection of sulfhydryl groups within the cell. PMID- 1444407 TI - Degradation of 2,4-dinitrophenol by two Rhodococcus erythropolis strains, HL 24-1 and HL 24-2. AB - Two Rhodococcus erythropolis strains, HL 24-1 and HL 24-2, were isolated from soil and river water by their abilities to utilize 2,4-dinitrophenol (0.5 mM) as the sole source of nitrogen. Although succinate was supplied as a carbon and energy source during selection, both isolates could utilize 2,4-dinitrophenol also as the sole source of carbon. Both strains metabolized 2,4-dinitrophenol under concomitant liberation of stoichiometric amounts of nitrite and 4,6 dinitrohexanoate as a minor dead-end metabolite. PMID- 1444408 TI - Initial hydrogenation during catabolism of picric acid by Rhodococcus erythropolis HL 24-2. AB - Rhodococcus erythropolis HL 24-2, which was originally isolated as a 2,4 dinitrophenol-degrading bacterium, could also utilize picric acid as a nitrogen source after spontaneous mutation. During growth, the mutant HL PM-1 transiently accumulated an orange-red metabolite, which was identified as a hydride Meisenheimer complex of picric acid. This complex was formed as the initial metabolite and further converted with concomitant liberation of nitrite. 2,4,6 Trinitrocyclohexanone was identified as a dead-end metabolite of the degradation of picric acid, indicating the addition of two hydride ions to picric acid. PMID- 1444409 TI - Distribution of viruses in the Chesapeake Bay. AB - High virus counts were found in water samples collected from the Chesapeake Bay. Viruses were enumerated by ultracentrifugation of water samples onto grids which were visualized by transmission electron microscopy. Virus counts in September 1990, April 1991, June 1991, August 1991, and October 1991 ranged between 2.6 x 10(6) and 1.4 x 10(8) viruses ml-1 with a mean of 2.5 x 10(7) viruses ml-1. Virus counts were usually at least three times higher than direct bacterial counts in corresponding samples. Virus counts in August and October were significantly higher than at the other sampling times, whereas bacterial counts were significantly lower at that time, yielding mean virus-to-bacterium ratios of 12.6 and 25.6, respectively. From analysis of morphology of the virus particles, it is concluded that a large proportion of the viruses are bacteriophages. The high virus counts obtained in this study suggest that viruses may be an important factor affecting bacterial populations in the Chesapeake Bay, with implications for gene transfer in natural aquatic bacterial populations and release of genetically engineered microorganisms to estuarine and coastal environments. PMID- 1444410 TI - DNA amplification polymorphisms of the cultivated mushroom Agaricus bisporus. AB - Single 10-bp primers were used to generate random amplified polymorphic DNA (RAPD) markers from commercial and wild strains of the cultivated mushroom Agaricus bisporus via the polymerase chain reaction. Of 20 primers tested, 19 amplified A. bisporus DNA, each producing 5 to 15 scorable markers ranging from 0.5 to 3.0 kbp. RAPD markers identified seven distinct genotypes among eight heterokaryotic strains; two of the commercial strains were shown to be related to each other through single-spore descent. Homokaryons recovered from protoplast regenerants of heterokaryotic strains carried a subset of the RAPD markers found in the heterokaryon, and both of the haploid nuclei from two heterokaryons were distinguishable. RAPD markers also served to verify the creation of a hybrid heterokaryon and to analyze meiotic progeny from this new strain: most of the basidiospores displayed RAPD fingerprints identical to that of the parental heterokaryon, although a few selected slow growers were homoallelic at a number of loci that were heteroallelic in the parent, suggesting that they represented rare homokaryotic basidiospores; crossover events between a RAPD marker locus and its respective centromere appeared to be infrequent. These results demonstrate that RAPD markers provide an efficient alternative for strain fingerprinting and a versatile tool for genetic studies and manipulations of A. bisporus. PMID- 1444411 TI - Effect of pseudobactin 358 production by Pseudomonas putida WCS358 on suppression of fusarium wilt of carnations by nonpathogenic Fusarium oxysporum Fo47. AB - Nonpathogenic Fusarium oxysporum Fo47b10 combined with Pseudomonas putida WCS358 efficiently suppressed fusarium wilt of carnations grown in soilless culture. This suppression was significantly higher than that obtained by inoculation of either antagonistic microorganism alone. The increased suppression obtained by Fo47b10 combined with WCS358 only occurred when Fo47b10 was introduced at a density high enough (at least 10 times higher than that of the pathogen) to be efficient on its own. P. putida WCS358 had no effect on disease severity when inoculated on its own but significantly improved the control achieved with nonpathogenic F. oxysporum Fo47b10. In contrast, a siderophore-negative mutant of WCS358 had no effect on disease severity even in the presence of Fo47b10. Since the densities of both bacterial strains at the root level were similar, the difference between the wild-type WCS358 and the siderophore-negative mutant with regard to the control of fusarium wilt was related to the production of pseudobactin 358. The production of pseudobactin 358 appeared to be responsible for the increased suppression by Fo47b10 combined with WCS358 relative to that with Fo47b10 alone. PMID- 1444412 TI - Organophosphonate utilization by the wild-type strain of Pseudomonas fluorescens. AB - The wild-type strain of Pseudomonas fluorescens was found to utilize a range of structurally diverse organophosphonates as its sole carbon or nitrogen sources. Representative compounds included aminoalkylphosphonates, hydroxyalkylphosphonates, oxoalkylphosphonates, and phosphono dipeptides. Among them, amino(phenyl)methylphosphonate,2-aminoethylphosphonate, aminomethylphosphonate, diisopropyl 9-aminofluoren-9-ylphosphonate, and 2 oxoalkylphosphonates were used by P. fluorescens as its sole sources of phosphorus. Only slight growth was observed on the herbicide glyphosate (N phosphonomethylglycine), which was metabolized to aminomethylphosphonate. Neither phosphinothricin nor its dialanyl tripeptide, bialaphos, supported growth of P. fluorescens. The possible mechanisms of organophosphonate degradation by this strain are discussed. PMID- 1444413 TI - Degradation of phenanthrene by Phanerochaete chrysosporium occurs under ligninolytic as well as nonligninolytic conditions. AB - In order to delineate the roles of lignin and manganese peroxidases in the degradation of polycyclic aromatic hydrocarbons by Phanerochaete chrysosporium, the biodegradation of phenanthrene (chosen as a model for polycyclic aromatic hydrocarbons) was investigated. The disappearance of phenanthrene from the extracellular medium and mycelia was determined by using gas chromatography. The disappearance of phenanthrene from cultures of wild-type strains BKM-F1767 (ATCC 24725) and ME446 (ATCC 34541) under ligninolytic (low-nitrogen) as well as nonligninolytic (high-nitrogen) conditions was observed. The study was extended to two homokaryotic (basidiospore-derived) isolates of strain ME446. Both homokaryotic isolates, ME446-B19 (which produces lignin and manganese peroxidases only in low-nitrogen medium) and ME446-B5 (which totally lacks lignin and manganese peroxidase activities), caused the disappearance of phenanthrene when grown in low- as well as high-nitrogen media. Moreover, lignin and manganese peroxidase activities were not detected in any of the cultures incubated in the presence of phenanthrene. Additionally, the mineralization of phenanthrene was observed even under nonligninolytic conditions. The results collectively indicate that lignin and manganese peroxidases are not essential for the degradation of phenanthrene by P. chrysosporium. The observation that phenanthrene degradation occurs under nonligninolytic conditions suggests that the potential of P. chrysosporium for degradation of certain environmental pollutants is not limited to nutrient starvation conditions. PMID- 1444414 TI - Identification of individual prokaryotic cells by using enzyme-labeled, rRNA targeted oligonucleotide probes. AB - A method to microscopically detect and identify individual cells of members of the domains Bacteria and Archaea is presented. rRNA-targeted oligonucleotides were 5' end labeled with the enzyme horseradish peroxidase and used for whole cell hybridization. Specifically bound probe was visualized by the enzymatic formation of an intracellular precipitate from the substrate diaminobenzidine. Permeation of the enzyme-labeled probe into whole fixed cells of gram-negative bacteria required their pretreatment with lysozyme-EDTA, whereas permeability of some archaebacterial cells was improved by addition of detergent to the hybridization buffer. Hitherto we had not achieved penetration of enzyme-labeled probe into gram-positive bacteria and yeast cells. This method should be a valuable tool for identification of suitable prokaryotic cells in environments with elevated background fluorescence or in situations in which an epifluorescence microscope is not available. PMID- 1444415 TI - Importance of unattached bacteria and bacteria attached to sediment in determining potentials for degradation of xenobiotic organic contaminants in an aerobic aquifer. AB - The bacterial abundance, distribution, and degradation potential (in terms of degradation versus lack of degradation) for four xenobiotic compounds in an aerobic aquifer sediment have been examined in laboratory and field experiments. The xenobiotic compounds studied were benzene, toluene, o-xylene, and naphthalene (all at concentrations of approximately 120 micrograms/liter). The aerobic degradation experiments ran for approximately 90 days at 10 degrees C, which corresponded to the groundwater temperature. At the end of the experiment, the major part of the microbial biomass, quantified as acridine orange direct counts, was attached to the groundwater sediment (18 x 10(6) to 25 x 10(6) cells per g [dry weight], and only a minor part was unattached in the groundwater (0.6 x 10(6) to 5.5 x 10(6) cells per ml). Experiments involving aquifer sediment suspensions showed identical degradation potentials in the laboratory and in the field. However, laboratory experiments involving only groundwater (excluding aquifer sediment) showed less degradation potential than in situ experiments involving only groundwater, indicating that the manipulation or approach of the laboratory experiments could affect the determination of the degradation potentials. No differences were observed between the groundwater-only and the sediment compartments in the in situ experiments in the ability to degrade the compounds, but the maximum degradation rates were substantially lower in the groundwater-only compartment. Preparations used in laboratory experiments for studying the degradation potential for xenobiotic organic contaminants should contain sediment to obtain the highest numbers of bacteria as well as the broadest and most stable degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444416 TI - Routine procedures for isolation and identification of enterococci and fecal streptococci. AB - Over the past 6 years, a revised classification of the streptococci and enterococci, based primarily on molecular techniques such as 16S rRNA sequencing and DNA-DNA hybridization, emerged. However, little attention was placed on routine physiological tests that could be used in food and clinical laboratories to differentiate between species of a new genus, Enterococcus, and fecal Streptococcus spp. The purpose of this study was to devise a convenient and reliable system to identify enterococci and fecal streptococci by using conventional procedures. Fifty-nine strains of 13 Enterococcus spp., including the type strains and many strains used by previous investigators, were characterized by using conventional tube tests, the API Rapid Strep system, and MicroScan Pos ID panels. Results were compared with each other and with previously published results. A comparison of conventional tube tests versus published tube test results yielded 17 discrepancies. Although not all tests were done with each of the three systems, 28 discrepancies between results obtained with the API system and those obtained with conventional tube tests were found. There were 24 discrepancies between results obtained with the MicroScan Pos ID panel and those obtained with conventional tube tests. There were 12 discrepancies between the results with the API Rapid Strep system and those with the MicroScan Pos ID panels. We devised flow charts of key tests that might be used to identify cultures without resorting to nucleic acid analysis and other labor- and equipment-intensive analyses. PMID- 1444417 TI - Lysogeny and bacteriocinogeny in Xenorhabdus nematophilus and other Xenorhabdus spp. AB - Induction by mitomycin or high-temperature treatment resulted in the production of bacteriocins and phages in both phases of Xenorhabdus nematophilus A24, indicating lysogeny. Phage DNA purified from X. nematophilus A24 hybridized to several fragments of DraI-digested A24 chromosomal DNA, confirming that the phage genome was incorporated into the bacterial chromosome. Bacteriocins and phages were detected in cultures of most other Xenorhabdus spp. after mitomycin or high temperature treatment. Xenorhabdus luminescens K80 was not lysed by these treatments, and no phages were seen associated with this strain. However, bacteriocins were detected in limited quantities in all Xenorhabdus cultures, including X. luminescens K80, without any induction. X. nematophilus A24 bacteriocins were antagonistic for other Xenorhabdus species but not for A24 or other strains of X. nematophilus. PMID- 1444418 TI - Cometabolic degradation of chlorinated alkenes by alkene monooxygenase in a propylene-grown Xanthobacter strain. AB - Propylene-grown Xanthobacter cells (strain Py2) degraded several chlorinated alkenes of environmental concern, including trichloroethylene, 1-chloroethylene (vinyl chloride), cis- and trans-1,2-dichloroethylene, 1,3-dichloropropylene, and 2,3-dichloropropylene. 1,1-Dichloroethylene was not degraded efficiently, while tetrachloroethylene was not degraded. The role of alkene monooxygenase in catalyzing chlorinated alkene degradations was established by demonstrating that glucose-grown cells which lack alkene monooxygenase and propylene-grown cells in which alkene monooxygenase was selectively inactivated by propyne were unable to degrade the compounds. C2 and C3 chlorinated alkanes were not oxidized by alkene monooxygenase, but a number of these compounds were inhibitors of propylene and ethylene oxidation, suggesting that they compete for binding to the enzyme. A number of metabolites enhanced the rate of degradation of chlorinated alkenes, including propylene oxide, propionaldehyde, and glucose. Propylene stimulated chlorinated alkene oxidation slightly when present at a low concentration but became inhibitory at higher concentrations. Toxic effects associated with chlorinated alkene oxidations were determined by measuring the propylene oxidation and propylene oxide-dependent O2 uptake rates of cells previously incubated with chlorinated alkenes. Compounds which were substrates for alkene monooxygenase exhibited various levels of toxicity, with 1,1-dichloroethylene and trichloroethylene being the most potent inactivators of propylene oxidation and 1,3- and 2,3-dichloropropylene being the most potent inactivators of propylene oxide-dependent O2 uptake. No toxic effects were seen when cells were incubated with chlorinated alkenes anaerobically, indicating that the product(s) of chlorinated alkene oxidation mediates toxicity. PMID- 1444419 TI - Genomic analysis of Pediococcus starter cultures used to control Listeria monocytogenes in turkey summer sausage. AB - The pulsed-field technique of clamped homogeneous electric field electrophoresis was employed to characterize and size genomic DNA of three pediocin-producing (Ped+) and two non-pediocin-producing (Ped-) strains of Pediococcus acidilactici. Comparison of genomic fingerprints obtained by digestion with the low-frequency cleavage endonuclease AscI revealed identical restriction profiles for four of the five strains analyzed. Summation of results for 10 individually sized AscI fragments estimated the genome length to be 1,861 kb for the four strains (H, PAC1.0, PO2, and JBL1350) with identical fingerprints. Genomic analysis of the pediocin-sensitive, plasmid-free strain P. acidilactici LB42 with the unique fingerprint revealed nine AscI fragments and a genome length of about 2,133 kb. Ped- (JBL1350) and Ped+ (JBL1095) starter cultures (one each) were used to separately prepare turkey summer sausage coinoculated with a four-strain Listeria monocytogenes mixture (ca. 10(5) CFU/g). The starter cultures produced equivalent amounts of acid during fermentation, but counts of L. monocytogenes were reduced to a greater extent in the presence of the Ped+ starter culture (3.4 log10 unit decrease) than in the presence of the Ped- starter culture (0.9 log10 unit decrease). Although no listeriae were recovered from sausages following the cook/shower, appreciable pediocin activity was recovered from sausages prepared with the Ped+ strain for at least 60 days during storage at 4 degrees C. The results of this study revealed genomic similarities among pediococcal starter cultures and established that pediocins produced during fermentation provide an additional measure of safety against listerial proliferation in turkey summer sausage. PMID- 1444420 TI - Role of heterotrophic bacteria in complete mineralization of trichloroethylene by Methylocystis sp. strain M. AB - Biodegradation experiments with radioactively labeled trichloroethylene showed that 32% of the radioactive carbon was converted to glyoxylic acid, dichloroacetic acid and trichloroacetic acid and that the same percentage was converted to CO2 and CO after 140 h of incubation by a pure culture of a type II methane-utilizing bacterium, Methylocystis sp. strain M, isolated from a mixed culture, MU-81, in our laboratory. In contrast, these water-soluble (14C)trichloroethylene degradation products were completely or partially degraded further and converted to CO2 by the MU-81 mixed culture. This phenomenon was attributed to the presence of a heterotrophic bacterium (strain DA4), which was identified as Xanthobacter autotrophicus, in the MU-81 culture. The results indicate that the heterotrophic bacteria play an important role in complete trichloroethylene degradation by methanotrophs. PMID- 1444421 TI - Hexadecane mineralization in oxygen-controlled sediment-seawater cultivations with autochthonous microorganisms. AB - Laboratory studies investigated the influence of dissolved oxygen tension (DOT) on microbial degradation of hexadecane in cultures with sediment-seawater suspensions. With a fermentor system, it was possible to adjust and regulate different oxic conditions (DOTs between 0.4 and 80% of oxygen saturation) as well as anoxia. The effects of DOT reduction on the amount and rate of hexadecane degraded and on the degree of mineralization and on the production of biomass were investigated. When the DOT was reduced from 80% to 5%, no dependence of the investigated parameters on the oxygen concentration was found. The amount of hexadecane degraded was constant, with an average value of 86% of the initially applied amount. The degradation rate was constant even down to 1% DOT, with an average value of 0.15 mg of hexadecane per g of sediment per h (16.2 mg liter-1 h 1). The mean degree of mineralization was 70% of the initially applied hexadecane, and biomass production reached a value of about 1.5 g per g of hexadecane consumed. A significant influence on the degradation process was detected only with DOTs below 1%. The degree of mineralization and the amount of degraded hexadecane decreased, whereas the degradation rate was still unaffected. Under anoxic conditions, no hexadecane degradation occurred within 190 h. The fact that the hexadecane biodegradation rate was constant down to at least 0.04% DOT shows that the actual oxygen concentration is of minor importance as long as the oxygen supply is high enough to guarantee the oxygen-dependent degradation step. PMID- 1444422 TI - Metabolism of hexadecyltrimethylammonium chloride in Pseudomonas strain B1. AB - A bacterium (strain B1) utilizing hexadecyltrimethylammonium chloride as a carbon and energy source was isolated from activated sludge and tentatively identified as a Pseudomonas sp. This bacterium only grew on alkyltrimethylammonium salts (C12 to C22) and possible intermediates of hexadecyltrimethylammonium chloride breakdown such as hexadecanoate and acetate. Pseudomonas strain B1 did not grow on amines. Simultaneous adaptation studies suggested that the bacterium oxidized only the alkyl chain of hexadecyltrimethylammonium chloride. This was confirmed by the stoichiometric formation of trimethylamine from hexadecyltrimethylammonium chloride. The initial hexadecyltrimethylammonium chloride oxygenase activity, measured by its ability to form trimethylamine, was NAD(P)H and O2 dependent. Finally, assays of aldehyde dehydrogenase, hexadecanoyl-coenzyme A dehydrogenase, and isocitrate lyase in cell extracts revealed the potential of Pseudomonas strain B1 to metabolize the alkyl chain via beta-oxidation. PMID- 1444423 TI - Establishment of polychlorinated biphenyl-degrading enrichment culture with predominantly meta dechlorination. AB - Enrichment of polychlorinated biphenyl (PCB)-dechlorinating microorganisms from PCB-contaminated sediments from the Upper Hudson River, N.Y., was attempted. The enrichment strategy was to use pyruvate as the electron donor and dechlorination of Aroclor 1242 as the electron acceptor. The enrichment medium also contained non-PCB-contaminated Hudson River sediments, which were required for the PCB dechlorinating activity. An enrichment culture (that had stable PCBT dechlorinating activity over nine serial transfers during 1 year) was established under these conditions; however, the rate of dechlorination did not increase after the second serial transfer. Dechlorination occurred primarily from the meta positions of the biphenyl molecule. Hydrogen could be substituted for pyruvate as the electron donor with equal activity, but when acetate was used as the electron donor a delay in dechlorination was observed. Sulfate and bromethane sulfonate inhibited dechlorination activity. The pyruvate-Aroclor 1242 enrichment also dechlorinated Aroclors 1248, 1254, and 1260; the extent of chlorine removed was the greatest for Aroclor 1254. For comparison, nonautoclaved non-PCB-contaminated Hudson River sediments used in the assay also dechlorinated Aroclors, but only after 12 to 16 weeks of incubation. This suggests that PCB-dechlorinating organisms were also present in these sediments but in numbers lower than those in the enrichment culture. PMID- 1444424 TI - Detection of virulence factors in culturable Escherichia coli isolates from water samples by DNA probes and recovery of toxin-bearing strains in minimal o nitrophenol-beta-D-galactopyranoside-4-methylumbelliferyl-beta-D-g luc uronide media. AB - A total of 449 Escherichia coli isolates in treated and raw water sources were submitted to DNA-DNA hybridization using seven different DNA probes to detect homology to sequences that code for Shiga-like toxins I and II; heat-stabile and heat-labile toxins, adherence factors EAF and eae, and the fimbrial antigen of entero-hemorrhagic E. coli. Fifty-nine (13%) of the isolates demonstrated homology with one or more specific DNA probes. More than 50% of the isolates in treated water were not recovered in MMO-4-methylumbelliferyl-beta-D-glucuronide media designed for detection of this indicator. PMID- 1444425 TI - A new assay for lignin-type peroxidases employing the dye azure B. AB - The discovery in 1983 of fungal "ligninases" capable of catalyzing the peroxidation of nonphenolic aromatic lignin components has been seen as a major advance in understanding how certain basidiomycete fungi can completely degrade lignin. The ability of these lignin-type peroxidases to covert millimolar concentrations of veratryl alcohol to veratraldehyde, indicated by a change in the A310 of veratraldehyde, has become the standard assay for routine quantitation of LP activity. A new assay based on the oxidation of micromolar concentrations of the dye Azure B is presented. Although it is as simple and rapid as the veratryl alcohol assay, it appears to overcome some of the shortcomings of that assay. In particular, interference from UV- and short wavelength visible-light-absorbing materials is greatly reduced and assay specificity is improved. PMID- 1444426 TI - Enhanced biodegradation of phenanthrene in oil tar-contaminated soils supplemented with Phanerochaete chrysosporium. AB - In recent years, the white rot fungus Phanerochaete chrysosporium has shown promise as an organism suitable for the breakdown of a broad spectrum of environmental pollutants, including polynuclear aromatic hydrocarbons (PAHs). The focus of this study was to determine whether P. chrysosporium could effectively operate in an actual field sample of oil tar-contaminated soil. The soil was loaded with [14C]phenanthrene to serve as a model compound representative of the PAHs. Soil with the native flora present under static, aerobic conditions with buffering (pH 5.0 to 5.5) displayed full mineralization on the order of 20% in 21 days. The addition of P. chrysosporium was synergistic, with full mineralization on the order of 38% in 21 days. In addition to full mineralization, there was an increase in the proportion of radiolabelled polar extractives, both soluble and bound, in the presence of P. chrysosporium. From this study, it is apparent that the native soil microflora can be prompted into full mineralization of PAHs in some contaminated soils and that this mineralization can be enhanced when supplemented with the white rot fungus P. chrysosporium. With further refinement, this system may prove an effective bioremediation technology for soils contaminated with PAHs. PMID- 1444427 TI - Rates of inactivation of waterborne coliphages by monochloramine. AB - A sophisticated water quality monitoring program was established to evaluate virus removal through Denver's 1-million-gal (ca. 4-million-liter)/day Direct Potable Reuse Demonstration Plant. As a comparison point for the reuse demonstration plant, Denver's main water treatment facility was also monitored for coliphage organisms. Through the routine monitoring of the main plant, it was discovered that coliphage organisms were escaping the water treatment processes. Monochloramine residuals and contact times (CT values) required to achieve 99% inactivation were determined for coliphage organisms entering and leaving this conventional water treatment plant. The coliphage tested in the effluent waters had higher CT values on the average than those of the influent waters. CT values established for some of these coliphages suggest that monochloramine alone is not capable of removing 2 orders of magnitude of these specific organisms in a typical water treatment facility. Electron micrographs revealed one distinct type of phage capable of escaping the water treatment processes and three distinct types of phages in all. PMID- 1444428 TI - Characterization of transcription initiation and termination signals of the proteinase genes of Lactococcus lactis Wg2 and enhancement of proteolysis in L. lactis. AB - The transcription initiation signals of the prtP and prtM genes specifying the proteolytic activity of Lactococcus lactis subsp. cremoris Wg2 were mapped by primer extension. The strength of these promoters was analyzed with promoter screening vector pGKV410, and they appeared to be weaker than previously isolated promoters of strain Wg2. In addition, a putative transcription terminator downstream of the prtP gene was characterized by using the terminator-screening vector pGKV259. The putative terminator decreased the transcription activity of lactococcal promoter P59 by approximately 70% in both Bacillus subtilis and L. lactis. Deletion of a part of the stem-loop structure of the terminator decreased the negative effect on transcription, indicating that the structure could indeed function as a terminator of transcription. The proteolytic activity of the lactococcal host was enhanced by placing the originally oppositely oriented prt genes in tandem and replacing the relatively weak promoters upstream of the prt genes with the stronger promoter, P32, from the chromosome of L. lactis Wg2. PMID- 1444429 TI - Metabolic and energetic control of Pseudomonas mendocina growth during transitions from aerobic to oxygen-limited conditions in chemostat cultures. AB - Several metabolic fluxes were analyzed during gradual transitions from aerobic to oxygen-limited conditions in chemostat cultures of Pseudomonas mendocina growing in synthetic medium at a dilution rate of 0.25 h-1. P. mendocina growth was glucose limited at high oxygen partial pressures (70 and 20% pO2) and exhibited an oxidative type of metabolism characterized by respiratory quotient (RQ) values of 1.0. A similar RQ value was obtained at low pO2 (2%), and detectable levels of acetic, formic, and lactic acids were determined in the extracellular medium. RQs of 0.9 +/- 0.12 were found at 70% pO2 for growth rates ranging from 0.025 to 0.5 h-1. At high pO2, the control coefficients of oxygen on catabolic fluxes were 0.19 and 0.22 for O2 uptake and CO2 production, respectively. At low pO2 (2%), the catabolic and anabolic fluxes were highly controlled by oxygen. P. mendocina showed a mixed-type fermentative metabolism when nitrogen was flushed into chemostat cultures. Ethanol and acetic, lactic, and formic acids were excreted and represented 7.5% of the total carbon recovered. Approximately 50% of the carbon was found as uronic acids in the extracellular medium. Physiological studies were performed under microaerophilic conditions (nitrogen flushing) in continuous cultures for a wide range of growth rates (0.03 to 0.5 h-1). A cell population, able to exhibit a near-maximum theoretical yield of ATP (YmaxATP = 25 g/mol) with a number of ATP molecules formed during the transfer of an electron towards oxygen along the respiration chain (P/O ratio) of 3, appears to have adapted to microaerophilic conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444430 TI - Evidence of hydrolytic route for anaerobic cyanide degradation. AB - Products observed during anaerobic cyanide transformation are consistent with a hydrolytic pathway (HCN + H2O <--> HCONH2 + H2O <--> HCOOH + NH3). Formate, the most frequently observed product, was generally converted to bicarbonate. Formamide was rapidly hydrolyzed to formate upon exposure to the anaerobic consortium but was not detected as an intermediate of cyanide transformation. PMID- 1444431 TI - Identification of geosmin as a volatile metabolite of Penicillium expansum. AB - Cultures of Penicillium expansum produce a musty, earthy odor. Geosmin [1,10 trans-dimethyl-trans(9)-decalol] was identified by gas chromatography-mass spectrometry from headspace samples of P. expansum cultures. Olfactory comparison of P. expansum cultures with a geosmin standard indicated geosmin is the primary component of the odor associated with P. expansum. PMID- 1444432 TI - Evaluation of the ability of primary selective enrichment to resuscitate heat injured and freeze-injured Listeria monocytogenes cells. AB - Resuscitation rates of injured Listeria monocytogenes on conventional selective Listeria enrichment broth and nonselective Trypticase soy broth containing 0.6% yeast extract were compared. Cells were heated to 60 degrees C for 5 min or frozen at -20 degrees C for 7 days. Inoculation of Trypticase soy broth-yeast extract with the stressed cells resulted in growth that was superior to that in Listeria enrichment broth. Injured cells were fully recovered at 6 to 8 h. PMID- 1444433 TI - A simple method to test condoms for penetration by viruses. AB - A method by which virus penetration through condoms can be tested with simple, inexpensive equipment is described. The method uses chi X174 bacteriophage as the challenge virus and physiologically relevant pressure. Penetration by 0.1 microliters (or less) of challenge suspension can be readily detected. As examples, latex and natural-membrane condoms were examined. PMID- 1444434 TI - Plasmids in Listeria monocytogenes in relation to cadmium resistance. AB - One hundred and seventy-three unrelated Listeria monocytogenes strains isolated from humans, animals, the environment, and food were analyzed for the presence of plasmids. Extrachromosomal DNA was found in 28% of the strains. Plasmid DNA was extracted more frequently from L. monocytogenes serogroup 1 strains (35%) than from serogroup 4 strains (15%). Among strains from food and the environment, 40% and 29%, respectively, harbored plasmids, whereas only 13% of the strains from humans and animals with listeriosis bore plasmids. We also investigated the susceptibility of 90 strains to seven antibiotics and four heavy-metal salts. No antibiotic resistance could be detected, but 95.3% of the plasmid-positive strains and only 12.7% of the plasmid-negative strains were resistant to cadmium. The plasmid-determined genetic basis of cadmium resistance was proven by conjugation between strains of L. monocytogenes and by cure of the plasmid. This is the first time that plasmids of L. monocytogenes have been shown to be associated with cadmium resistance. PMID- 1444435 TI - Rapid determination of members of the family Enterobacteriaceae in drinking water by an immunological assay using a monoclonal antibody against enterobacterial common antigen. AB - An immunological method for the detection of members of the family Enterobacteriaceae in drinking water was developed. The method was based on a sandwich enzyme-linked immunosorbent assay (ELISA) with monoclonal antibody immunoglobulin G2a 898 against enterobacterial common antigen. The enterobacterial common antigen sandwich ELISA combined with selective preenrichment culture could be performed in only 24 h. Six hundred sixty-eight water samples from a variety of German public water supplies were screened to verify the effectiveness of the new method. Ninety-eight percent of the results obtained by the immunological method could be confirmed by conventional microbiological methods. The immunological method proved to be considerably faster and more specific and sensitive than the standard method specified by the German drinking water regulations. PMID- 1444436 TI - Metabolic by-products of anaerobic toluene degradation by sulfate-reducing enrichment cultures. AB - Two dead-end metabolites of anaerobic toluene transformation, benzylsuccinic acid and benzylfumaric acid, accumulated in sulfate-reducing enrichment cultures that were fed toluene as the sole carbon source. Stable isotope-labeled toluene and gas chromatography-mass spectrometry were used to confirm that the compounds resulted from toluene metabolism. The two metabolites constituted less than 10% of the toluene carbon (over 80% was mineralized to carbon dioxide, according to a previous study). This study demonstrates that the novel nonproductive pathway proposed by Evans and coworkers (P. J. Evans, W. Ling, B. Goldschmidt, E. R. Ritter, and L. Y. Young, Appl. Environ. Microbiol. 58:496-501, 1992) for a denitrifying pure culture applies to disparate anaerobic bacteria. PMID- 1444437 TI - Influence of 2,4,6-trinitrotoluene (TNT) concentration on the degradation of TNT in explosive-contaminated soils by the white rot fungus Phanerochaete chrysosporium. AB - The ability of Phanerochaete chrysosporium to bioremediate TNT (2,4,6 trinitrotoluene) in a soil containing 12,000 ppm of TNT and the explosives RDX (hexahydro-1,3,5-trinitro-1,3,5- triazine; 3,000 ppm) and HMX (octahydro-1,3,5,7 tetranitro-1,3,5,7-tetrazocine; 300 ppm) was investigated. The fungus did not grow in malt extract broth containing more than 0.02% (wt/vol; 24 ppm of TNT) soil. Pure TNT or explosives extracted from the soil were degraded by P. chrysosporium spore-inoculated cultures at TNT concentrations of up to 20 ppm. Mycelium-inoculated cultures degraded 100 ppm of TNT, but further growth was inhibited above 20 ppm. In malt extract broth, spore-inoculated cultures mineralized 10% of added [14C]TNT (5 ppm) in 27 days at 37 degrees C. No mineralization occurred during [14C]TNT biotransformation by mycelium-inoculated cultures, although the TNT was transformed. PMID- 1444438 TI - Comparison of selected methods for the enumeration of fecal coliforms and Escherichia coli in shellfish. AB - In a comparison of five selected methods for the enumeration of fecal coliforms and Escherichia coli in naturally contaminated and sewage-seeded mussels (Choromytilus spp.) and oysters (Ostrea spp.), a spread-plate procedure with mFC agar without rosolic acid and preincubation proved the method of choice for routine quality assessment. PMID- 1444439 TI - Acetate oxidation by dissimilatory Fe(III) reducers. PMID- 1444440 TI - Purification and characterization of dihydrobenzophenanthridine oxidase from elicited Sanguinaria canadensis cell cultures. AB - Upon treatment of Papaveracea cells with fungal elicitors, the biosynthesis of benzo[c]phenanthridine alkaloids is induced. Dihydrobenzophenanthridine oxidase, which catalyzes a later step in the biogenesis of these alkaloids, is one of the enzymes whose activity is elevated in the process. Here we report the 211-fold purification of the oxidase from elicited Sanguinaria canadensis by a combination of ammonium sulfate fractionation, DEAE-Sephadex, CM-Sephadex, Sephadex G-200, and either phenyl Superose or gel filtration chromatography. The purified enzyme utilized molecular oxygen to oxidize dihydrosanguinarine to sanguinarine with concomitant formation of hydrogen peroxide. A pH optimum of 7.0, Vmax of 27 nkat/mg protein, and apparent Km of 6.0 microM for dihydrosanguinarine were determined. Dihydrochelerythrine was also found to be a substrate for the purified enzyme, displaying an apparent Km of 10 microM. However, neither dihydronorsanguinarine nor the indole alkaloid ajmalicine was oxidized, indicating that the enzyme has some substrate specificity. Apparent molecular weight estimates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the most purified enzyme preparation obtained contained a major component of 77 kDa and two minor components between 59 and 67 kDa that can be associated with oxidase activity. Purified enzyme preparations possessed activity that was inhibited by sodium diethyldithiocarbamate, sodium azide, potassium cyanide, 1,4-DL-dithiothreitol, and mercaptoethanol. PMID- 1444441 TI - Reactions of thrombin-serpin complexes with thrombospondin. AB - Activated platelets release proteins that form stable complexes with thrombin (J. J. Miller, P. C. Browne, and T. C. Detwiler, Biochem. Biophys. Res. Commun. 151, 9-15, 1988). A working model for the reaction (P. C. Browne, J. J. Miller, and T. C. Detwiler, Arch. Biochem. Biophys. 265, 534-538, 1988) includes a dissociable complex of thrombin with released platelet protease nexin, leading to formation of a nondissociable thrombin-nexin complex that then becomes disulfide linked to thrombospondin. This disulfide-linked complex is converted back to the thrombin nexin complex by reduction of disulfide bonds. Results that allow elaboration on this model are presented. After longer periods of incubation or after incubation with higher concentrations of thrombin, the amount of thrombin complexed with thrombospondin exceeded the amount of thrombin-nexin complex recovered after reduction of disulfide bonds. When the reaction mixture included inhibitors of formation of the thrombin-nexin complex, a slow formation of the thrombin thrombospondin complex was observed. It was concluded that there is a nexin independent as well as the faster nexin-dependent disulfide linkage of thrombin to thrombospondin. Addition of thrombin-antithrombin III complexes to the supernatant solution of activated platelets also led to complexes with thrombospondin, demonstrating that serpins other than platelet protease nexin facilitate incorporation of thrombin into complexes with thrombospondin. By heparin affinity chromatography, it was shown that thrombin-nexin complexes dissociably associate with thrombospondin prior to formation of disulfide-linked complexes. These observations are incorporated into a more detailed model of the reaction. PMID- 1444442 TI - Monomaleimidogold labeling of the gamma subunit of the Escherichia coli F1 ATPase examined by cryoelectron microscopy. AB - A novel approach for locating sites of interest in a protein complex has been developed using monomaleimidonanogold (MMN). The Escherichia coli F1 ATPase, when prepared without the delta subunit, contains only a single reactive cysteine on one of the three copies of the alpha subunit. This site was reacted with MMN and the gold cluster visualized on the protein complex by cryoelectron microscopy. Additional sites for modification with MMN were added by introducing cysteine residues through site-directed mutagenesis. Labeling of two mutants, gamma S8-C and gamma T106-C, in which Ser8 and Thr106, respectively, had been replaced by a cysteine, placed the gold cluster on the central mass that is seen in the hexagonal projection of the ECF1 complex. The results establish that the central mass contains the N-terminal part of the gamma subunit. PMID- 1444443 TI - Post-transcriptional regulation of mouse renal cytochrome P450 2E1 by testosterone. AB - Our previous studies demonstrated that the sex-related difference in renal metabolism of N-nitrosodimethylamine in C3H/HeJ mouse was due to the sexual dichotomy of cytochrome P450 2E1 (P450 2E1) and that renal P450 2E1 in female mouse was inducible by testosterone. The present study demonstrates that the sex related difference in renal P450 2E1 and the testosterone-mediated regulation also occurred in other mouse strains studied. The time- and dose-responses in the testosterone-mediated regulation of P450 2E1 were characterized. 19 Nortestosterone, an analog of testosterone, was shown to have an effect on the regulation of mouse renal P450 2E1 similar to that of testosterone. Testicular feminized mice (Tfm, a mouse strain devoid of functional androgen receptors) had about only one-tenth the renal P450 2E1 mRNA level as the wild-type male mice and testosterone treatment of the Tfm mice had no effect on the level of renal P450 2E1 mRNA. The result suggests that androgen receptor plays an important role in the sex- and testosterone-related regulation of mouse renal P450 2E1. To study the mechanism of the sex-related and testosterone-mediated regulation of P450 2E1 mRNA in mouse kidney, the transcription rate of the P450 2E1 gene was measured by a nuclear run-on transcription assay. Although the kidneys of male and testosterone-treated female mice had much higher steady-state levels of P450 2E1 mRNA, their transcription rates of the P450 2E1 gene were not higher than the kidneys of untreated female mice. This result suggests that the sex- and testosterone-related regulation of mouse renal P450 2E1 is predominantly at the post-transcriptional level. PMID- 1444444 TI - Interaction of mitochondrially bound rat brain hexokinase with intramitochondrial compartments of ATP generated by oxidative phosphorylation and creatine kinase. AB - Previous work led to the conclusion that, during oxidative phosphorylation, mitochondrially bound hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) from rat brain was dependent on intramitochondrially compartmented ATP as substrate. The present study demonstrated that, when oxidative phosphorylation was functioning concurrently, mitochondrial creatine kinase could also generate intramitochondrial ATP serving as substrate for hexokinase. In the absence of concurrent oxidative phosphorylation, the kinetics of glucose phosphorylation with ATP generated by creatine kinase were not consistent with the supply of ATP from a saturable intramitochondrial compartment as formed during oxidative phosphorylation. Evidence for intramitochondrially compartmented ATP, generated by creatine kinase, was obtained; this was distinct from compartmented ATP generated by oxidative phosphorylation in terms of kinetics of generation of the compartment and its capacity, sensitivity to release by carboxyatractyloside, and sensitivity to disruption by digitonin. That oxidative phosphorylation did induce a dependence on intramitochondrial ATP as a substrate was further indicated by the observation that, although the initial rate of glucose phosphorylation by mitochondrial hexokinase depended on the extramitochondrial concentration of ATP present at the time oxidative phosphorylation was initiated, a final steady state rate of glucose phosphorylation was attained that was independent of extramitochondrial ATP levels. These and previous results emphasize the probable importance of nucleotide compartmentation in regulation of cerebral glycolytic and oxidative metabolism. PMID- 1444445 TI - Effects of ligands on reduction of oxygen by vanadium(IV) and vanadium(III). AB - V(IV) and V(III) reduce molecular oxygen with increasing rates as the pH is raised from 6.0 to 7.4. Under all conditions tested, V(IV) is the more efficient reductant. EDTA and ATP generally inhibit the reduction of oxygen by V(III) and V(IV). In contrast, desferrioxamine accelerates the reduction of oxygen by V(IV) but with decreasing effectiveness at pH 7.4 compared to pH 6.0, while desferrioxamine accelerates the reduction of oxygen by V(III) only at pH 6.0. Histidine enhances the reduction of oxygen by V(IV) at pH 7.0 and 7.4. The observed rates of oxygen reduction by V(III) and V(IV) imply that the intracellular distribution of vanadium among its redox states reflects not an equilibrium but a steady state. PMID- 1444446 TI - Inactivation of Escherichia coli 2-amino-3-ketobutyrate CoA ligase by phenylglyoxal and identification of an active-site arginine peptide. AB - Treatment of homogeneous preparations of 2-amino-3-ketobutyrate CoA ligase from Escherichia coli, a pyridoxal 5'-phosphate-dependent enzyme, with phenylglyoxal, 4-(oxyacetyl)phenoxyacetic acid, 2,3-butanedione, or 1,2-cyclohexanedione results in a time- and concentration-dependent loss of enzymatic activity. Phenylglyoxal in 50 mM phosphate buffer (pH 7.0) is the most effective modifier, causing > 95% inactivation within 20 min at 25 degrees C. Controls establish that this inactivation is not due to modifier-induced dissociation or photoinduced nonspecific alteration of the ligase. The substrate, acetyl CoA, or the coenzyme, pyridoxal 5'-phosphate, gives > 50% protection against inactivation. Enzyme partially inactivated by phenylglyoxal has the same Km value for glycine but the Vmax decreases in proportion to the observed level of inactivation. Whereas the native apoligase shows good recovery of activity with time in parallel with an increase in 428-nm absorptivity when incubated with pyridoxal 5'-phosphate, no such effects are seen with the phenylglyoxal-modified apoligase. Reaction of the enzyme with [14C]phenylglyoxal allowed for the isolation of a peptide which, by amino acid composition and sequencing data, was found to correspond to residues 349-378 in the intact enzyme. These results indicate that arginine residue-366 and/or residue-368 in the primary structure of E. coli 2-amino-3-ketobutyrate ligase is at the active site. PMID- 1444447 TI - Catalytic properties of the human cytochrome P450 2E1 produced by cDNA expression in mammalian cells. AB - A full-length cDNA encoding human cytochrome P450 2E1 was expressed in mammalian cell lines using the vaccinia virus expression system. Immunoblot analysis showed that the expressed protein reacted with a polyclonal antibody against rat 2E1 and comigrated with P450 2E1 from human liver microsomes. P450 2E1 expressed in Hep G2 cells, a human cell line which contains both cytochrome b5 and NADPH:P450 oxidoreductase, was able to metabolize several known P450 2E1 substrates: N nitrosodimethylamine (NDMA), N-nitrosomethylbenzylamine (NMBzA), p-nitrophenol, phenol, and acetaminophen. Apparent Km and Vmax values for NDMA demethylation were 22 microM and 173 pmol/min/mg microsomal protein, respectively. P450 2E1 expressed in TK-143 cells, which do not contain b5, displayed Km and Vmax values of 31 microM and 34 pmol/min/mg microsomal protein, respectively. Incorporation of purified rat liver b5 into TK-143 microsomes increased the Vmax 2.2-fold and decreased the Km to 22 microM. Addition of b5 to Hep G2 microsomes resulted in a 1.6-fold increase in Vmax, but showed no effect on the Km. P450 2E1 expressed in Hep G2 cells was shown to metabolize NMBzA with a Km of 47 microM and Vmax of 213 pmol/min/mg microsomal protein. Addition of b5 lowered the Km to 27 microM, but had no effect on Vmax. These results demonstrate conclusively that P450 2E1 is responsible for the low Km forms of NDMA demethylase and NMBzA debenzylase observed in liver microsomes and that these activities are affected by cytochrome b5. PMID- 1444448 TI - Hormonal regulation of rat renal cytochrome P450s by androgen and the pituitary. AB - The hormonal regulation of rat renal cytochrome P450s, P450 4A2 (K-5) and K-2, was investigated. The level of P450 4A2 in male rats was five times that in female rats and accounted for some 90% of total cytochrome P450, measured photometrically. Lauric acid omega- and (omega-1)-hydroxylation activities of renal microsomes of male rats were also higher than those of female rats. The sex differences in lauric acid hydroxylation activity seemed to arise from the differences in P450 4A2 concentrations, according to an immunochemical study. P450 K-2 was a female-dominant form in rat kidneys. The level of P450 K-2 in renal microsomes of male rats was one-tenth that of P450 4A2. Castration of male rats decreased the levels of P450 4A2 and treatment of castrated male rats with testosterone reversed the decrease. The castration of male rats decreased the lauric acid hydroxylation of the renal microsomes to the level of female rats. The administration of testosterone to castrated male rats reversed the decrease. Hypophysectomy of male rats decreased the level of P450 4A2 and the administration of growth hormone reversed the decrease when intermittent injections mimicking the male secretory pattern were given, although continuous administration mimicking the female secretory pattern did not. Castration of male rats did not affect the level of P450 K-2, but testosterone decreased its level. Hypophysectomy of male rats increased the level of P450 K-2 and growth hormone decreased its level in hypophysectomized rats. These results suggested that the expression of P450 4A2 was regulated by androgen or growth hormone and regulation of P450 4A2 was different from that of P450 K-2. To explore the regulation of renal cytochrome P450 further, testosterone was given to control (intact) or hypophysectomized adult female rats. P450 4A2 was induced in the kidneys of both control and hypophysectomized female rats to close to the level of male rats. Thus, P450 4A2 was directly regulated by testosterone as well as growth hormone, and the regulation of the male-dominant form in rat kidneys was different from that of the male-specific form in the rat liver, which is regulated mostly by growth hormone. PMID- 1444449 TI - Direct electrochemistry of thioredoxins and glutathione at a lipid bilayer modified electrode. AB - By using direct electrochemical analysis we have established that the reduction of Escherichia coli thioredoxin (EcT), T4 thioredoxin (T4T), and glutathione (GSSG) occurs at a self-assembled lipid bilayer-modified gold electrode via two separate one-electron processes. The first electron transfer has half-wave potentials of -0.05 +/- 0.01, -0.07 +/- 0.01, and -0.06 +/- 0.01 V, whereas the second one has values of -0.48 +/- 0.01, -0.39 +/- 0.01, and -0.45 +/- 0.01 V, for EcT, T4T, and GSSG, respectively. The scan-rate dependence of the cyclic voltammetry indicates, for both waves, that the process of electron transfer is dominated by a bulk diffusion of free species to and from the electrode, and that strongly adsorbed species do not significantly contribute at the scan rates used. The voltage separation of the peak currents indicates a quasi-reversible electron transfer process with an electrochemical rate constant which is larger for the second (lower potential) electron than for the first one. Using the above half wave potentials of the one-electron steps, one can calculate a thermodynamic half wave potential for the two-electron reduction processes. The values of these potentials are -0.265, -0.23, and -0.25 V for EcT, T4T, and GSSG, respectively. These are in excellent agreement with literature values obtained from equilibrium measurements of enzyme-catalyzed reactions involving these species. It is quite clear from these results that lipid bilayer-modified electrodes provide a biocompatible and direct means of efficiently carrying out electrochemical reactions with sulfur-based redox systems, as we have previously shown to be the case with metalloproteins. PMID- 1444450 TI - Human mitochondrial aldehyde dehydrogenase substrate specificity: comparison of esterase with dehydrogenase reaction. AB - Substrate specificity of human mitochondrial low Km aldehyde dehydrogenase (EC 1.2.1.3) E2 isozyme has been investigated employing p-nitrophenyl esters of acyl groups of two to six carbon atoms and comparing with that of aldehydes of one to eight carbon atoms. The esterase reaction was studied under three conditions: in the absence of coenzyme, in the presence of NAD (1 mM), and in the presence of NADH (160 microM). The maximal velocity of the esterase reaction with p nitrophenyl acetate and propionate as substrates in the presence of NAD was 3.9 4.7 times faster than that of the dehydrogenase reaction. Under all other conditions the velocities of dehydrogenase and esterase reactions were similar; the lowest kcat was for p-nitrophenyl butyrate in the presence of NAD. Stimulation of esterase activity by coenzymes was confined to esters of short acyl chain length; with longer acyl chain lengths or increased bulkiness (p nitrophenyl guanidinobenzoate) no effect or even inhibition was observed. Comparison of kinetic constants for esters demonstrates that p-nitrophenyl butyrate is the worst substrate of all esters tested, suggesting that the active site topography is uniquely unfavorable for p-nitrophenyl butyrate. This fact is, however, not reflected in kinetic constants for butyraldehyde, which is a good substrate. The substrate specificity profile as determined by comparison of kcat/Km ratios was found to be quite different for aldehydes and esters. For aldehydes kcat/Km ratios increased with the increase of chain length; with esters under all three conditions, a V-shaped curve was produced with a minimum at p nitrophenyl butyrate. PMID- 1444451 TI - Effects of temperature acclimation on the expression of hepatic cytochrome P4501A mRNA and protein in the fish Fundulus heteroclitus. AB - Previous studies showed that hydrocarbon induction of hepatic microsomal monooxygenase activity is attenuated in the teleost fish Fundulus heteroclitus acclimated to low temperature. The basis of that attenuation, and the effects of temperature on monooxygenase activity, were examined by analyzing liver cytochrome P4501A (CYP1A) mRNA, protein, and catalytic activity in control and beta-naphthoflavone (BNF)-treated F. heteroclitus acclimated to 6 or 16 degrees C. There were no temperature-related differences in total P450 content, NADPH cytochrome c (P450) reductase activity, ethoxyresorufin O-deethylase (EROD) activity, or immunoquantified CYP1A content in hepatic microsomes of untreated fish. Fish acclimated to 16 degrees C and given a single intraperitoneal injection of BNF exhibited a rapid rise and fall in CYP1A mRNA content and an induction of EROD activity and CYP1A protein that was undiminished over 7 days. Similarly treated fish acclimated at 6 degrees C showed an increase in CYP1A mRNA content greater than that in 16 degrees C fish, but with no significant increase in EROD activity or CYP1A content over 7 days. Examined over a longer term, microsomal EROD activity was significantly induced by BNF in fish at both temperatures; activity peaked at 5-7 days in 16 degrees C fish, while in 6 degrees C fish the activity continued to rise slowly over 25 days. However, the greatest activity reached in 6 degrees C fish (0.68 nmol/min/mg) was less than half that seen in the warmer animals (1.46 nmol/min/mg). Immunodetectable CYP1A content showed the same trend as EROD activity, and the turnover number (nmol product formed/min/nmol CYP1A) for EROD activity was about the same in all groups, indicating that concentration of the catalyst alone could account for the different patterns of microsomal activity. CYP1A mRNA content was again induced to a similar degree by BNF in both the 6 and the 16 degrees C fish; the apparent half-life of the mRNA was substantially longer in cold-acclimated than in warm acclimated BNF-treated fish. Comparing the levels of CYP1A mRNA and protein at the two acclimation temperatures following BNF treatment indicates that translational activity, rather than transcriptional activity, is the sensitive point in the effect of temperature on CYP1A induction in these fish. PMID- 1444452 TI - Ethanol and oleate inhibition of alpha-ketoisovalerate and 3-hydroxyisobutyrate metabolism by isolated hepatocytes. AB - Ethanol inhibited glucose synthesis from alpha-ketoisovalerate by isolated rat hepatocytes without significant inhibition of flux through the branched-chain alpha-ketoacid dehydrogenase complex. Accumulation of 3-hydroxyisobutyrate, an intermediate in the catabolism of alpha-ketoisovalerate, was increased by ethanol, indicating inhibition of flux at the level of 3-hydroxyisobutyrate dehydrogenase. 3-Hydroxybutyrate caused the same effects as ethanol, suggesting inhibition was a consequence of an increase in the mitochondrial NADH/NAD+ ratio. Flux through the 3-hydroxyisobutyrate dehydrogenase was more sensitive to regulation by the mitochondrial NADH/NAD+ ratio than flux through the branched chain alpha-ketoacid dehydrogenase. Oleate also inhibited glucose synthesis from alpha-ketoisovalerate, but marked inhibition of flux through the branched-chain alpha-ketoacid dehydrogenase complex was caused by this substrate. PMID- 1444453 TI - Biosynthesis of monoterpenes: inhibition of (+)-pinene and (-)-pinene cyclases by thia and aza analogs of the 4R- and 4S-alpha-terpinyl carbocation. AB - (+)-Pinene cyclase (synthase) from Salvia officinalis leaf catalyzes the cyclization of geranyl pyrophosphate, via (3R)-linalyl pyrophosphate and the (4R) alpha-terpinyl cation, to (+)-alpha-pinene and to lesser quantities of stereochemically related monoterpene olefins, whereas (-)-pinene cyclase converts the same achiral precursor, via (3S)-linalyl pyrophosphate and the (4S)-alpha terpinyl cation, to (-)-alpha-pinene and (-)-beta-pinene and to lesser amounts of related olefins. Racemic thia analogs of the linalyl and alpha-terpinyl carbocation intermediates of the reaction sequence were previously shown to be good uncompetitive inhibitors of monoterpene cyclases, and inhibition was synergized by the presence of inorganic pyrophosphate. These results suggested that the normal reaction proceeds through a series of carbocation:pyrophosphate anion paired intermediates. Both the (4R)- and the (4S)-thia and -aza analogs of the alpha-terpinyl cation were prepared and tested as inhibitors with the antipodal pinene cyclases, both in the absence and in the presence of inorganic pyrophosphate. Although the inhibition kinetics were complex, cooperative binding of the analogs and inorganic pyrophosphate was demonstrated, consistent with ion pairing of intermediates in the course of the normal reaction. Based on the antipodal reactions catalyzed by the pinene cyclases, stereochemical differentiation between the (4R)- and the (4S)-analogs was anticipated; however, neither enzyme effectively distinguished between enantiomers of the thia and aza analogs of the alpha-terpinyl carbocation. Enantioselectivity in the enzymatic conversion of (RS)-alpha-terpinyl pyrophosphate to limonene by the pinene cyclases was also examined. Consistent with the results obtained with the thia and aza analogs, the pinene cyclases were unable to discriminate between enantiomers of alpha-terpinyl pyrophosphate in this unusual reaction. Either the alpha-terpinyl antipodes are too similar to allow differentiation by the pinene cyclases, or these enzymes lack an inherent requirement to distinguish the (4R)- and (4S)-forms because they encounter only one enantiomer in the course of the normal reaction from geranyl pyrophosphate. PMID- 1444454 TI - Evidence for an essential histidine residue in 4S-limonene synthase and other terpene cyclases. AB - (4S)-Limonene synthase, isolated from glandular trichome secretory cell preparations of Mentha x piperita (peppermint) leaves, catalyzes the metal ion dependent cyclization of geranyl pyrophosphate, via 3S-linalyl pyrophosphate, to (-)-(4S)-limonene as the principal product. Treatment of this terpene cyclase with the histidine-directed reagent diethyl pyrocarbonate at a concentration of 0.25 mM resulted in 50% loss of enzyme activity, and this activity could be completely restored by treatment of the preparation with 5 mM hydroxylamine. Inhibition with diethyl pyrocarbonate was distinguished from inhibition with thiol-directed reagents by protection studies with histidine and cysteine carried out at varying pH. Inactivation of the cyclase by dye-sensitized photooxidation in the presence of rose bengal gave further indication of the presence of a readily modified histidine residue. Protection of the enzyme against inhibition with diethyl pyrocarbonate was afforded by the substrate geranyl pyrophosphate in the presence of Mn2+, and by the sulfonium ion analog of the linalyl carbocation intermediate of the reaction in the presence of inorganic pyrophosphate plus Mn2+, suggesting that an essential histidine residue is located at or near the active site. Similar studies on the inhibition of other monoterpene and sesquiterpene cyclases with diethyl pyrocarbonate suggest that a histidine residue (or residues) may play an important role in catalysis by this class of enzymes. PMID- 1444455 TI - Sublethal oxidant stress induces a reversible increase in intracellular calcium dependent on NAD(P)H oxidation in rat alveolar macrophages. AB - A concentration-dependent elevation of intracellular calcium ([Ca2+]i) and oxidation of NAD(P)H occurred in alveolar macrophages during exposure to sublethal tert-butylhydroperoxide concentrations (tBOOH) (< or = 100 microM in 1 ml with 1 x 10(6) cells). Oxidation of NAD(P)H preceded a rise in [Ca2+]i. The elevation of [Ca2+]i was reversible at < 50 microM tBOOH exposure and the return to the steady state [Ca2+]i correlated temporally with repletion of NAD(P)H. At > 50 microM tBOOH, the changes in NAD(P)H and [Ca2+]i were sustained. The relative contributions of NADPH and NADH oxidation were examined by varying the substrates supplying reducing equivalents and by inhibiting glutathione reductase activity. The results suggested that at < 50 microM tBOOH, oxidation of NADPH predominated, while at > 50 microM tBOOH, NADH oxidation predominated. A complex relationship between the relative roles of NADPH and NADH oxidation and the elevation of [Ca2+]i was revealed: (i) reversible oxidation of NADPH is associated with the initial and reversible elevation of [Ca2+]i at < 50 microM tBOOH; (ii) the sustained elevation of [Ca2+]i at > 50 microM tBOOH correlates with the sustained oxidation of NADH; and (iii) the changes in [Ca2+]i did not depend on influx of extracellular Ca2+. We speculate that at low tBOOH, Ca2+ was released from the NADPH/NADP(+)-sensitive mitochondrial Ca2+ pool while higher tBOOH caused additional Ca2+ release from GSH/GSSG-sensitive nonmitochondrial Ca2+ pools with sustained elevation of [Ca2+]i due to decreased mitochondrial Ca2+ reuptake. PMID- 1444456 TI - Regulation of sex pheromone biosynthesis in the housefly, Musca domestica: relative contribution of the elongation and reductive steps. AB - The regulation of production of the sex pheromone (Z)-9-tricosene (Z9-23:Hy) in the housefly, Musca domestica, was studied by examining the chain length specificity of the fatty acyl-CoA elongation reactions and the reductive conversion of fatty acyl-CoAs to alkenes in 1- and 4-day-old male and female houseflies. Microsomal preparations from 4-day-old female insects produced as the predominant alkene Z9-23:Hy when incubated with malonyl-CoA, NADPH, and [9,10 3H2]oleoyl-CoA (18:1-CoA), whereas microsomal preparations from 4-day-old male insects produced predominantly (Z)-9-heptacosene (Z9-27:Hy). These are the major alkenes produced in vivo by Day 4 females and males, respectively. Microsomes prepared from both Day 1 males and Day 1 females produced Z9-27:Hy as the major alkene from labeled 18:1-CoA. This is the major alkene produced in vivo by both sexes at Day 1. An examination of the chain length specificity of the elongation reactions showed that microsomes prepared from Day 4 male insects readily elongated both 18:1-CoA and 15-[15,16-3H2]tetracosenoyl-CoA (24:1-CoA) to 28 carbon moieties, whereas microsomes from Day 4 female insects did not efficiently elongate either substrate beyond 24 carbons. With high substrate concentrations, microsomes prepared from male insects converted 24:1-CoA to Z9-23:Hy more efficiently than did those from females, whereas under lower and presumably more physiological substrate concentrations, microsomes from females had slightly higher activity than did those from males. Taken together, these data show that the regulation of the chain length of the alkenes, and thus sex pheromone production, in the housefly resides predominantly in the elongation reactions and not in the step which converts the fatty acyl-CoA to hydrocarbon. PMID- 1444457 TI - Differentiation of HL-60 cells by phorbol ester is correlated with up-regulation of protein kinase C-alpha. AB - To clarify the mechanism of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced macrophage-like differentiation of HL-60 cells, we investigated the correlation between the effects of protein kinase C (PKC) inhibitors on the induction of markers of TPA-induced differentiation and those on suggested critical steps of the differentiation. H-7, sphingosine, and trifluoroperazine significantly suppressed TPA-induced cell adhesion but their effects on the induction of acid phosphatase and nonspecific esterase differed among the inhibitors. The three inhibitors failed to affect on TPA-induced annexin I expression. In contrast, staurosporine markedly suppressed the induction of all these markers. The effects of the inhibitors on some suggested critical steps of the differentiation, a rapid phosphorylation of specific proteins, a rapid membrane association of PKC, and down-regulation of PKC at 18 h after addition of TPA, were not correlated with those on the differentiation marker induction. Only the effect of the inhibitors on up-regulation of PKC-alpha was closely correlated with TPA-induced annexin I expression; staurosporine inhibited up-regulation of PKC-alpha but other inhibitors did not similarly affect the induction of annexin I expression. These results suggest that PKC-alpha is intimately related to macrophage-like differentiation of HL-60 cells by TPA. PMID- 1444458 TI - Differential effects of iron and inflammation on ferritin synthesis on free and membrane-bound polyribosomes of rat liver. AB - We have examined the distribution of ferritin mRNA to free and endoplasmic reticulum (ER)-bound liver polyribosomes during inflammation and iron treatment of rats. Postnuclear tissue supernatants were fractionated on a discontinuous sucrose gradient developed to separate free and bound polyribosomes. Total RNA recovered averaged 3.2 mg/g tissue, 40% of which was with ER and 30% with the free polyribosomes, about 25% being with the postribosomal/RNP fraction. Slot blot hybridization of equal portions of RNA revealed that 12 h after injection of turpentine to induce inflammation, ferritin mRNA was concentrated on the ER-bound polyribosomes, while it was concentrated on the free polyribosomes 2 h after injection of ferric ammonium citrate. Differences were highly significant, based on multiple determinations and densitometry. Profiles of ferritin mRNA distribution on linear sucrose gradients corroborated the differential findings. Concentrations of total ferritin mRNA per gram liver doubled with iron treatment but were not significantly different 12 h after turpentine treatment. At the same time point after turpentine, ferritin protein synthesis was increased twofold, as measured by the 1 h incorporation of [14C]leucine. We conclude that a significant portion of ferritin mRNA always associates with the ER-bound polyribosomes, and that inflammation and iron differentially alter the polysomal distribution of ferritin mRNA, suggesting that two different kinds of mRNA may be involved. PMID- 1444459 TI - Mechanism of activation of the NAD-malic enzyme from Ascaris suum by fumarate. AB - The mechanism of activation of the NAD-malic enzyme from Ascaris suum by fumarate has been probed using initial velocity studies, deuterium isotope effects, and isotope partitioning of the E:Mg:malate complex. Fumarate exerts its activating effect by decreasing the off-rate for malate from the E:Mg:malate and E:NAD:Mg:malate complexes. Fumarate is a positive heterotropic effector of the NAD-malic enzyme at low concentrations (K act approximately 0.05 mM) and an inhibitor competitive against malate (Ki approximately 25 mM). The activation by fumarate results in a decrease in the Ki malate and an increase in V/K malate of about 2-fold, while the maximum velocity remains constant. Isotope partitioning studies of E:Mg:[14C]malate indicate that the presence of fumarate results in a decrease in the malate off-rate constant by about 2.2-fold. The deuterium isotope effects on V and V/K malate are both 1.6 +/- 0.1 in the absence of fumarate, while in the presence of 0.5 mM fumarate DV is 1.6 +/- 0.1 and D(V/K malate) is 1.1 +/- 0.1. These data are also consistent with a decrease in the off-rate for malate from E:NAD:Mg:malate, resulting in an increase in the forward commitment factor for malate and manifested as a lower value for D(V/K malate). There is a discrimination between active and activator sites for the binding of dicarboxylic acids, with the activator site preferring the extended configuration of 4-carbon dicarboxylic acids, while the active site prefers a configuration in which the 4 carboxyl is twisted out of the C1-C3 plane. The physiologic importance and regulatory properties of fumarate in the parasite are also discussed. PMID- 1444460 TI - Lec15 cells transfer glucosylated oligosaccharides to protein. AB - B4-2-1 cells (Lec15 cells) are Chinese hamster ovary cells deficient in mannosylphosphoryldolichol synthase activity. They synthesize the truncated lipid intermediate Man5GlcNAc2-P-P-dolichol rather than the Glc3Man9GlcNAc2-P-P dolichol synthesized by wild-type cells. In this report we present evidence that these cells did synthesize glucosylated Man5GlcNAc2-P-P-dolichol, but this species represented only a minor fraction of the labeled oligosaccharide-lipid. On the other hand, glucosylated oligosaccharides were a major species transferred to protein in these cells, showing that in vivo, glucosylated oligosaccharides are preferentially transferred to protein. The truncated oligosaccharides found in B4-2-1 cells were removed from the protein by N-glycanase treatment, since they were resistant to both endo-beta-N-acetylglucosaminidase H and F activity. B4-2-1 cells processed the glucosylated, truncated oligosaccharides transferred to G protein of vesicular stomatitis virus, leading to infectious virus. PMID- 1444461 TI - Glutathione S-transferases of human lung: characterization and evaluation of the protective role of the alpha-class isozymes against lipid peroxidation. AB - Glutathione S-transferase (GST) isozymes of human lung have been purified, characterized, quantitated, and, based on their structural and immunological profiles, identified with their respective classes. The tau-, mu-, and alpha class GSTs represented 94, 3, and 3% activities of total human lung GSTs toward CDNB, respectively, and 60, 10, and 30% of total GST protein, respectively. Both the mu- and the alpha-class GSTs of human lung exhibited heterogeneity. The two mu-class GSTs of human lung had pI values of 6.5 and 6.25 and were differentially expressed in humans. Significant differences were seen between the kinetic properties of these two isozymes and also between the lung and liver mu-class GSTs. The alpha-class GST isozymes of lung resolved into three peaks during isoelectric focusing corresponding to pI values of 9.2, 8.95, and 8.8. All three alpha-class GSTs isozymes had blocked N-termini and were immunologically similar to human liver alpha-class GSTs. Peptide fingerprints generated by SV-8 protease digestion and CNBr cleavage indicated minor structural differences between the liver and the lung alpha-class GSTs. The three alpha-class GSTs of lung expressed glutathione peroxidase activities toward the hydroperoxides of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylglycerol, with Km values in the range of 22 to 87 microM and Vmax values in the range of 67-120 mol/mol/min, indicating the involvement of the alpha-class GSTs in the protection mechanisms against peroxidation. All three classes of lung GSTs expressed activities toward leukotriene A4 methyl ester and epoxy stearic acid but the mu class GSTs had relatively higher activities toward these substrates. PMID- 1444462 TI - Molecular cloning of the chicken gizzard telokin gene and cDNA. AB - Telokin is a protein which consiste of the C-terminal portion of smooth muscle myosin light chain kinase (MLCK) (M. Ito, R. Dabrowska, V. Guerriero, Jr., and D. J. Hartshone (1989) J. Biol. Chem. 264, 13971-13974). In this study, the chicken gizzard telokin cDNA and gene were cloned and analyzed. The telokin cDNA coded 157 amino acid residues which were completely identical to the C-terminal portion of the amino acid sequence of chicken gizzard MLCK. The telokin gene was coded in a 6.3-kb EcoRI genomic fragment and it consisted of three exons. The 5'-leader sequence of the telokin cDNA and genomic sequence revealed that the telokin gene was included in the MLCK gene and the transcription started in the intronic sequence of the MLCK gene. The analysis of the telokin gene suggests that the telokin expression was under the control of an independent promotor. Northern blotting and the reverse transcriptase-polymerase chain reaction methods revealed that telokin was expressed not only in chicken gizzard but also in chicken heart, lung, intestine, and skeletal muscle although the levels of the expression in the latter were much less than that in the gizzard. PMID- 1444463 TI - Tissue-specific expression, induction, and inhibition through metabolic intermediate-complex formation of guinea pig cytochrome P450 belonging to the CYP2B subfamily. AB - The tissue-specific expression and induction of P450GP-1, a constitutive form of cytochrome P450 of the guinea pig classified into the CYP2B subfamily, were studied. Prior to these studies, a P450 form (P450GP-1 PB) was purified from phenobarbital-treated guinea pigs and the properties were compared with those of the P450GP-1. This form was judged to be the same as P450GP-1 existing in untreated animals by comparisons of their N-terminal amino acid sequences, peptide maps, and affinities toward anti-P450GP-1 antibody. Immunostaining of P450GP-1 revealed that the lung and small intestine as well as the liver of untreated guinea pigs contain P450GP-1, while none or only small amounts of this P450 form were observed in the kidney, heart, spleen, urinary bladder, and testis. The amount of liver P450GP-1 protein expressed in untreated guinea pigs was estimated to be 19.4% of the total cytochrome P450 and this form was increased 1.7-fold by phenobarbital treatment. Similarly, intestinal P450GP-1 was increased by phenobarbital treatment. However, lung P450GP-1 was not increased by the treatment. It was also observed that the liver P450GP-1 is induced with SKF 525A to the same extent as with phenobarbital. On the other hand, dexamethsone, p,p'-dichlorodiphenyltrichloroethane, and isosafrole showed no or only a weak ability to increase the liver P450GP-1 content. The drug-metabolizing activities in the liver microsomes of SKF-525A-pretreated guinea pigs were lower than those in phenobarbital-treated animals, although the P450GP-1 protein was induced equally by these treatments. The low activities of SKF-525A-treated animals in the drug metabolisms were attributed to the formation of the metabolic intermediate complex between P450GP-1 and SKF-525A metabolite. These results permitted us to conclude that the tissue specificity in the expression of guinea pig P450 belonging to the CYP2B subfamily and the inducibility with chemicals are similar to those of rat CYP2B1, although the constitutive expression of guinea pig liver P450GP-1 is much higher than that of CYP2B1. PMID- 1444464 TI - Binding of pulmonary surfactant protein A to galactosylceramide and asialo-GM2. AB - The binding of pulmonary surfactant protein A (SP-A) to glycolipids was examined in the present study. The direct binding of SP-A on a thin-layer chromatogram was visualized using 125I-SP-A as a probe. 125I-SP-A bound to galactosylceramide and asialo-GM2, but failed to exhibit significant binding to GM1, GM2, asialo-GM1, sulfatide, and Forssman antigen. The study of 125I-SP-A binding to glycolipids coated onto microtiter wells also revealed that SP-A bound to galactosylceramide and asialo-GM2. SP-A bound to galactosylceramides with non-hydroxy or hydroxy fatty acids, but showed no binding to either glucosylceramide or galactosylsphingosine. Excess native SP-A competed with 125I-SP-A for the binding to asialo-GM2 and galactosylceramide. Specific antibody to rat SP-A inhibited 125I-SP-A binding to glycolipids. In spite of chelation of Ca2+ with EDTA or EGTA, SP-A retained a significant binding to glycolipids. Inclusion of excess monosaccharides in the binding buffer reduced the glycolipid binding of SP-A, but failed to achieve complete abolishment. The oligosaccharide isolated from asialo GM2 is also effective at reducing 125I-SP-A binding to the solid-phase asialo GM2. From these data, we conclude that SP-A binds to galactosylceramide and asialo-GM2, and that both saccharide and ceramide moieties in the glycolipid molecule are important for the binding of SP-A to glycolipids. PMID- 1444465 TI - Synthesis of high-affinity, hydrophobic monosaccharide derivatives and study of their interaction with concanavalin A, the pea, the lentil, and fava bean lectins. AB - Concanavalin A (Con A) and agglutinins from the pea (PSA), lentil (LCH), and fava bean (VFA) constitute a group of D-mannose/D-glucose binding legume lectins. In addition to their sugar binding specificity, these lectins also contain sites that bind hydrophobic ligands. The present study explores a class of nonpolar binding sites reportedly present adjacent to the carbohydrate binding site in PSA, LCH, and VFA. A series of 2-O- and 3-O-substituted nitrobenzoyl and nitrobenzyl derivatives of methyl alpha-D-glucopyranoside and methyl alpha-D mannopyranoside were synthesized. Evaluation of their binding to Con A, PSA, LCH, and VFA was carried out by the technique of hapten inhibition of precipitation reaction. The hapten inhibition assay results reveal that the presence of a methyl or methylene group at the O-2 or O-3 position of the sugar is essential for hydrophobic interaction with PSA, LCH, and VFA. The substitution of methyl by nitrobenzyl leads to enhanced binding (1.7-16.7 times for the 2-O-substituted compounds and 7.9-40.5 times for the 3-O-substituted compounds) with the m nitrobenzyl group contributing to maximum binding. A hydrophobic interaction is also involved between Con A and 2-O-nitrobenzyl derivatives, resulting in enhanced binding, but the corresponding 3-O-isomers bind poorly due probably to steric reasons. These results may be rationalized on the basis of the recently published X-ray data of Con A and VFA. The nitrobenzyl derivatives, after transformation to their azido analogs, have potential applications in the photoaffinity labeling of these lectins. PMID- 1444466 TI - Effects of cationic polypeptides on the activity, substrate interaction, and autophosphorylation of casein kinase II: a study with calmodulin. AB - The effects of basic polypeptides on the ability of casein kinase II to phosphorylate an exogenous substrate (calmodulin) are correlated with steady state autophosphorylation of the alpha- and beta-subunits of casein kinase II. Polylysine and polyarginine increase autophosphorylation of the alpha-subunit with a concomitant decrease in beta-subunit phosphorylation, while enhancing casein kinase II-stimulated phosphorylation of calmodulin over 100-fold. The highly basic carboxyl terminal segment of the endogenous p21c-Ki-ras has similar effects on the phosphorylation of calmodulin and the alpha- and beta-subunits of casein kinase II. Altering the concentration of cationic polypeptides produces a biphasic effect on the phosphorylation of both calmodulin and the alpha-subunit, which correlate positively with each other but do not correlate with beta-subunit phosphorylation. When the KCl concentration is changed, casein kinase II activity correlates positively only with alpha-subunit phosphorylation. In contrast, the biphasic response of calmodulin phosphorylation by casein kinase II at different Ca2+ concentrations correlates positively with both alpha- and beta-subunit phosphorylation. Therefore, in the presence of basic protein activators, the rate of phosphorylation of a substrate, calmodulin, correlates with steady-state phosphorylation of the alpha-subunit, but not with the beta-subunit under all conditions tested. Endogenous cationic factors may modulate the in vivo activity of casein kinase II and alter the interaction of the enzyme with specific intracellular substrates. PMID- 1444467 TI - Identification of arginyl residues involved in the binding of ferredoxin-NADP+ reductase from Anabaena sp. PCC 7119 to its substrates. AB - Ferredoxin-NADP+ reductase from the cyanobacterium Anabaena sp. PCC 7119 was chemically modified by the alpha-dicarbonyl reagent phenylglyoxal. The studies of the inactivation by this compound, which is specific for arginyl residues, of both the diaphorase and NADPH-cytochrome c reductase activities, characteristic of the enzyme, are indicative of the involvement of at least one group of this kind in the binding site of NADP+ and a second one implicated in the interaction with ferredoxin. After specific cleavage of a FNR sample incubated with [7 14C]phenylglyoxal, two major labeled peptides were identified. The peptide which exhibited the higher degree of modification corresponded to residues 208-242. It contained four arginine residues but only two of them were the target of the modification: Arg224 and Arg233. Protection studies with protein substrates and sequence comparison with other reductases allow us to propose that these residues in Anabaena sp. PCC 7119 FNR must be involved in the interaction with the pyridine nucleotide. The second peptide corresponds to residues 75-103 and although it contains three arginine residues, Arg77 is the only one that exhibits the modification. This residue seems to be a key one in the interaction of this reductase with ferredoxin. PMID- 1444468 TI - The MgATPase activity of rat cardiac sarcoplasmic reticulum is a function of the calcium ATPase protein. AB - Magnesium-dependent ATPase (MgATPase) activity is associated with many E1-E2 or P type transport ATPases including the sarcoplasmic reticulum (SR) calcium ATPase. The SR isolated from rat heart has a MgATPase activity which is 6-12 times faster than the MgATPase activity of the SR isolated from dog heart. To determine the origin of the high MgATPase activity of rat heart SR, we compared and contrasted cardiac SR isolated from both species. The preparations were similar in the following ways: (i) contamination by other organelles; (ii) the comigration of MgATPase activity with calcium-dependent ATPase (CaATPase) activity through a sucrose gradient; (iii) a similar ATPase activity sensitivity to pH and ATP concentration; (iv) the high and similar of sensitivity of ATPase activity to detergent; and (v) a similar protein profile. In both preparations, a single protein in the 105,000-Da region of polyacrylamide gels was phosphorylated by ATP, and the phosphorylated species was an acylphosphate formed in the presence and absence of calcium. Dimethyl sulfoxide, which slows acylphosphoenzyme breakdown, markedly inhibited both CaATPase and MgATPase activities of both preparations but not other enzyme activities. Importantly, the specific inhibitor of the SR calcium pump, thapsigargin, completely inhibited the CaATPase activity with an I50 of 6-7 nM; however, a higher concentration (I50 of 2 microM) was required to inhibit the MgATPase activity of the rat cardiac SR. These results provide evidence that the MgATPase activity of rat cardiac SR is part of the enzyme cycle of the calcium ATPase protein. PMID- 1444469 TI - Effects of mutations at residue 309 of the large subunit of ribulosebisphosphate carboxylase from Synechococcus PCC 6301. AB - Previous studies [G. S. Hudson et al. (1989) J. Biol. Chem. 265, 808-814] showed that the faster turnover rates and lower affinities for CO2 of ribulosebisphosphate carboxylase/oxygenases from C4 plants, compared to C3 and C3/C4 plants, were specified by the chloroplast-encoded large subunits. In pairs of closely related C3 and C4 species from three genera, these kinetic changes were accompanied by only three to six amino acid residue substitutions, depending on the genus. None of these substitutions occurred near the active site and only one, 309Met (C3) to Ile (C4), was common to all three genera. Unlike the plant carboxylases, the highly homologous enzyme from the cyanobacterium Synechococcus PCC 6301 folds and assembles properly when its rbcL and rbcS genes are coexpressed in Escherichia coli. Furthermore, the cyanobacterial enzyme has Ile at position 309 of the large subunit, a high turnover number, and a poor affinity for CO2. 309Ile was replaced with Met and several other residues by site-directed mutagenesis of the cyanobacterial rbcL. Met and Leu were tolerated at this position with no alteration in the kinetic or structural properties of the assembled holoenzyme. However, substitution with Val, Gly, Trp, or Arg prevented the assembly of the subunits. The indifference to Met or Ile at this position, as well as the tolerance for Leu which is not observed with any natural ribulosebisphosphate carboxylase, leads to the conclusion that either the 309Met/Ile substitution has no effect on the kinetic properties of the plant enzyme, despite the correlation apparent in previous studies, or the cyanobacterial enzyme is sufficiently different from the plant enzyme in other respects that the influence of residue 309 is masked. PMID- 1444470 TI - The interaction of Trolox C, a water-soluble vitamin E analog, with ferrylmyoglobin: reduction of the oxoferryl moiety. AB - The oxidation of the heme iron of metmyoglobin by H2O2 yields an oxo ferryl complex (FeIV = O), similar to Compound II of peroxidases, as well as a protein radical; this high oxidation state of myoglobin is known as ferrylmyoglobin. The interaction of Trolox, a water-soluble vitamin E analog, with ferrylmyoglobin entailed two sequential one-electron oxidations of the phenolic antioxidant with intermediate formation of a phenoxyl radical and accumulation of a quinone end product. These oxidation reactions were linked to individual reductions of ferrylmyoglobin to metmyoglobin, as indicated by the value of the relationship [metmyoglobin]formed/[Trolox]consumed: 1.92 +/- 0.28. The Trolox-mediated reduction of ferrylmyoglobin to metmyoglobin could proceed directly, i.e., electron transfer from the phenolic-OH group in Trolox to the oxoferryl moiety, or indirectly, i.e., sequential electron transfer from Trolox to a protein radical to the oxoferryl moiety. The former mechanism is supported by the finding that the high oxidation heme iron is reduced under conditions where the tyrosyl residues are blocked by o-acetylation and when hemin is substituted for myoglobin. The latter mechanism is consistent with the following observations: (a) the EPR signal ascribed to the protein radical is suppressed by Trolox, with the concomitant appearance of the EPR spectrum of the Trolox phenoxyl radical and (b) the rate of ferrylmyoglobin reduction by Trolox is decreased with increasing number of tyrosyl residues in the proteins of horse myoglobin (titrated by o acetylation) and sperm whale myoglobin. The apparent discrepancy between these observations can be reconciled by considering that both electrophilic centers in ferrylmyoglobin--the oxoferryl heme moiety and the protein radical--function independently of each other and that recovery of ferrylmyoglobin by Trolox could be effected through the tyrosyl residues, albeit at slower rates. The mechanistic aspects of these results are discussed in terms of the two main redox transitions in the myoglobin molecule encompassing valence changes of the heme iron and electron transfer of the tyrosyl residue in the protein and linked to the two sequential one-electron oxidations of Trolox. PMID- 1444471 TI - Activation of protein kinase C isozymes by contractile stimuli in arterial smooth muscle. AB - Protein kinase C (PKC) has been proposed to be involved in the regulation of vascular smooth muscle (VSM) contractile activity. However, little is known in detail about the activation of this kinase or specific isozymes of this kinase by contractile stimuli in VSM. As an index of PKC activation, Ca(2+)- and phospholipid-dependent histone IIIS kinase activity was measured in the particulate fraction from individual strips of isometrically contracting carotid arterial smooth muscle. Phorbol 12,13-dibutyrate (PDB) increased PKC activity in the particulate fraction (155% over resting value by 15 min) with a time course which paralleled or preceded force development. Stimulation with the agonist histamine (10(-5) M) resulted in rapid increases in both force and particulate fraction PKC activity which was maximal by 2 min (increase of 139%) and partially sustained over 45 min (increase of 41%). KCl (109 mM), which evokes a sustained contractile response, caused a slow increase (124% by 45 min) in particulate fraction PKC activity. No significant increases in activator-independent histone kinase activity were observed in response to any stimulus tested. PKC alpha and PKC beta were identified as the principal Ca2+/phospholipid-dependent PKC isozymes expressed in this tissue. In unstimulated arterial tissue, the ratio of immunodetectable isozyme content (alpha:beta) was estimated to be 1:1 in the particulate and 1.5:1 in the cytosolic fractions. Upon stimulation with each of the three contractile stimuli, particulate fraction PKC content assessed by immunoblotting increased with a time course and to an extent comparable to the observed changes in PKC activity. There was no evidence of differential regulation of the PKC alpha or -beta isozymes by PDB compared to the other contractile stimuli. These results indicate that diverse contractile stimuli are capable of tonically activating PKC in preparations of functional smooth muscle, and are consistent with a functional role for PKC alpha and/or -beta in the regulation of normal smooth muscle contractile activity. PMID- 1444472 TI - Antioxidant effect of manganese. AB - The antioxidant effects of manganese and other transition metals were studied as the inhibition of microsomal lipid peroxidation and crocin bleaching by peroxyl radicals. The peroxyl radical scavenging capacity was measured by competition kinetics analysis. While Zn(II), Ni(II), and Fe(II) were almost completely ineffective, Mn(II) and Co(II) showed a free radical scavenging capacity, exhibiting relative rate constant ratios respectively of 0.513 and 0.287. This indicates that Mn(II) is by far the most active. Therefore, the chain-breaking antioxidant capacity of Mn(II) seems to be related to the rapid quenching of peroxyl radicals according to the reaction R-OO. + Mn(II) + H(+)-->ROOH+Mn(III). The antioxidant mechanism is discussed considering the different reduction potentials of the examined cations. PMID- 1444473 TI - The specificity and elastinolytic activities of bovine cathepsins S and H. AB - Cathepsins S and H were purified from bovine spleen and their catalytic properties compared. The enzymes were shown to be similar by chromatographic properties and by the ability to hydrolyze Bz-Phe-Val-Arg-NHMec. They could however be distinguished by the fact that cathepsin S reacted with Z-[125I]Tyr Ala-CHN2 and hydrolyzed Z-Phe-Arg-NHMec whereas cathepsin H did not. The substrate and inhibitor specificities of cathepsin H suggest that unlike cathepsins B, L, and S, it cannot accommodate peptides with aromatic side chains in P2. Cathepsins L and S can accommodate the aromatic side chain of tyrosine in P1 readily, whereas cathepsins H and B cannot. The specificities of each enzyme for synthetic substrates and inhibitors have enabled the construction of models of the architecture of the active sites of the mammalian cysteine proteinases which clearly show the differences between the four enzymes. A significant characteristic of cathepsin S is that it can hydrolyze insoluble elastin at both acidic and neutral pH; this distinguishes it from all of the other lysosomal proteinases. PMID- 1444474 TI - Studies on the holoenzyme biogenesis of the spinach ferredoxin-NADP+ reductase. AB - An expression plasmid, pPreFNR, in which the DNA sequence coding for the spinach ferredoxin-NADP+ reductase precursor was under the control of prokaryotic transcription and translation initiation signals has been constructed. The plasmid directed the synthesis in Escherichia coli of a 43-kDa immunoreactive polypeptide which could be identified with the reductase preprotein. Analyses of bacterial extracts showed that the precursor was unstable and devoid of catalytic activities, suggesting that the presence of the transit peptide would not allow the assembly in E. coli of an active preholoenzyme. Furthermore, the reductase precursor was found to undergo a processing in E. coli. The proteolysed form, which retained 13 of the 55 residues of the transit peptide, was active, suggesting that removal of the first 42 residues of the presequence enabled the protein to properly fold and to bind the FAD prosthetic group in the bacterial host, as it was previously shown in the case of the mature form of the spinach reductase. PMID- 1444475 TI - Akazara scallop troponin C: Ca(2+)-induced conformational change and interaction with rabbit troponin subunits. AB - The number of specific Ca2+ bound to Akazara scallop troponin C was estimated to be 0.7 with an apparent binding constant of 5 x 10(5) M-1 (T. Ojima and K. Nishita, 1986, J. Biol. Chem. 261, 16749-16754). In the present paper, we report on the Ca(2+)-induced conformational changes in the troponin C and the interaction of the troponin C with rabbit troponin subunits. The Ca2+ binding to the troponin C caused a marked change in difference uv absorption spectra and a retardation of elution on Sephacryl S-200 gel filtration. However, its circular dichroism spectrum was hardly changed by the Ca2+ binding. These results suggest that the Ca2+ binding to the troponin C induced changes predominantly in tertiary structure rather than in secondary structure. Akazara scallop troponin C was shown to be able to bind to rabbit troponin I-Cellulofine affinity column, but the affinity was not greatly increased by Ca2+ unlike the case of rabbit troponin C. On hybridizing with rabbit troponin T and I, Akazara scallop troponin C was shown to be incapable of substituting rabbit troponin C; i.e., the hybrid troponin strongly inhibited the Mg-ATPase activity of rabbit actomyosin tropomyosin irrespective of the presence or absence of Ca2+, thus recovering no Ca2+ sensitivity. PMID- 1444476 TI - Crystal structure of peroxynitrite-modified bovine Cu,Zn superoxide dismutase. AB - The crystal structure of bovine Cu,Zn superoxide dismutase modified with peroxynitrite (ONOO-) was determined by X-ray diffraction, utilizing the existing three-dimensional model of the native structure deposited in the Brookhaven Protein Data Bank (J. A. Tainer et al., J. Mol. Biol. 160, 181-217, 1982). The native structure and the modified derivative were refined to R factors of 19.0 and 18.7% respectively using diffraction data from 6.0 to 2.5 A. The major result after reaction with peroxynitrite was the appearance of electron density 1.45 A from a single epsilon carbon of Tyr-108, the only tyrosine residue in the sequence. Tyr-108 is a solvent-exposed residue 18 A from the copper atom in the active site. The electron density was consistent with nitration of Tyr-108 at one of the epsilon carbons to form 3-nitrotyrosine. We propose that the nitration occurs in solution by transfer of a nitronium-like species from the active site on one superoxide dismutase dimer to the Tyr-108 of a second dimer. PMID- 1444477 TI - Binding of cytosolic aconitase to the iron responsive element of porcine mitochondrial aconitase mRNA. AB - The 5' end of porcine mitochondrial aconitase mRNA contains an iron responsive element (IRE)-like secondary structure (T. Dandekar, R. Stripecke, N. K. Gray, B. Goosen, A. Constable, H. E. Johansson, and M. W. Hentze (1991) EMBO J. 10, 1903 1909). A protein from a liver extract binds to a mitochondrial aconitase RNA probe and supports the identification of this sequence as an IRE. Purified cytosolic aconitase but not the mitochondrial enzyme binds to this IRE as well as to a ferritin IRE. All forms of cytosolic aconitase, [4Fe-4S] enzyme, [3Fe-4S] enzyme and apoenzyme bind with similar affinity. A Kd of 0.25 nM was calculated for the apoaconitase-IRE interaction from Scatchard analysis. These results support the conclusion that cytosolic aconitase is an IRE-binding protein which may regulate translation of mitochondrial aconitase mRNA. PMID- 1444478 TI - CA074 methyl ester: a proinhibitor for intracellular cathepsin B. AB - The specificity of compound CA074 [N-(L-3-trans-propylcarbamoyloxirane-2 carbonyl)-L-isoleucyl-L-pro line] for the inactivation of cathepsin B was quantified in in vitro measurements with cysteine endopeptidases from cattle, it being found that the compound is a very rapid inactivator of cathepsin B (rate constant 112,000 M-1.s-1), with barely detectable action on cathepsins H, L, and S or m-calpain. Conversion of the proline carboxyl group of the inhibitor to the methyl ester virtually abolished the effect on cathepsin B, and a possible explanation for the importance of the carboxyl is presented on the basis of the tertiary structure of cathepsin B. It was found that CA074 methyl ester (1 microM, 3 h) caused selective inactivation of the intracellular cathepsin B of human gingival fibroblasts in culture, in contrast to other available agents, and we suggest that CA074 methyl ester will be of value in the elucidation of the biological functions of cathepsin B. PMID- 1444479 TI - [Present status of gene diagnosis in cancer]. AB - Advances in molecular genetics in the past decade enabled us to analyze the cause of mendelian disorders at molecular level and a variety of mutations, not only in point mutations and deletion in exons but also in those occurred in regulatory elements or in RNA processing have been precisely identified. Such a variety of mutations may constitute variable clinical manifestations even in the simple mendelian disorders. On the other hand, pathogenesis of common diseases is much complicated and remains greatly to be elucidated. However, if we could use the strategies applied in the past few years for mendelian disorders, it seems to be not difficult to approach them. It is recommended to categorize a certain disease into subgroups for distinguishing their heterogenous phenotypes by clinical, biochemical and other properties. Owing to the success in making a subgroup (FAB classification), many subtype-specific translocations were found in leukemia, and then, rearrangement of relevant genes is also being shown. The best example is seen in chronic myelocytic leukemia. Since rearrangement of ABL and BCR was shown and both genes were cloned, detection of minimal residual diseases after intensive treatment became possible at 10(-6) level using RT-PCR technique. Recently developed interphase cytogenetics using FISH has visualized Ph1 translocation in metaphase cells and also in round nuclei, suggesting a potential use in monitoring the effect of certain drugs during treatment. Furthermore, very selective targeting therapy is being devised using antisense DNA. PMID- 1444480 TI - [New analogues of methotrexate]. AB - New antifolate antimetabolites are currently developed and three analogues of methotrexate (MTX) (Trimetrexate, Edatrexate, TNP-351) are undergoing clinical trials in Japan. Trimetrexate characteristically enters cells primarily by passive transport, which is different from the mechanism of MTX. The increased therapeutic efficacy of Edatrexate is expected, because of the higher concentration of polyglutamates than MTX in tumor cells. TNP-351 is a novel antifolate, which has a different chemical structure from other antifolates. The current state of clinical trials of three antifolates and the indications for chemotherapy of lung cancer are reviewed. PMID- 1444481 TI - [Enhancement of the effects of anticancer agents on B16 melanoma cells by combination with cepharanthine--I. Alkaloids]. AB - The anticancer effect of a podophyllotoxin derivative, etoposide (ETOP), and the vinca alkaloids, vincristine (VCR) and vindesine (VDS), on the colony forming efficiency (CFE) of B16 melanoma cells, and the CFE inhibition by the combination with a biscoclaurine alkaloid, Cepharanthine (Ceph) were studied in vitro. By combination with Ceph, CFE was reduced about 44% for ETOP, 31% for VCR and 30% for VDS compared to CFE without Ceph. Therefore, the effect of each anticancer agent was enhanced by combination with Ceph, especially that of Ceph and ETOP. The combination effect was greater when the low concentration of the agents was used. From the present study, the combination of ETOP and Ceph appears to be the more effective form of treatment. PMID- 1444482 TI - [Enhancement of the effects of anticancer agents on B16 melanoma cells by combination with cepharanthine--II. Antimetabolite, alkylating agent, nitrosourea]. AB - We have studied chemotherapy enhancement by the combination of the biscoclaurine alkaloid, Cepharanthine (Ceph), using the inhibition of colony forming efficiency (CFE) of B16 melanoma cells in vitro. Hydroxyurea, antimetabolite, showed a time dependent inhibition of CFE, and the combination with Ceph enhanced CFE inhibition by 29%, which is stable and independent of the treatment time. Dacarbazine, a biological alkylating agent, given with Ceph showed a time dependent inhibition of CFE (43%). MCNU, a nitrosourea, with Ceph showed the greatest inhibition of CFE (67%) among the anticancer agents used. The CFE inhibition was time-dependent and required a higher concentration of MCNU. In this series of studies using CFE inhibition of B16 melanoma cells in vitro, etoposide showed the best effect by the combination with Ceph, which seems to be a candidate for in vivo evaluation. PMID- 1444483 TI - [Concentration of 5-fluorouracil in the blood and tissues of gastric and colo rectal cancer patients after oral administration of UFT]. AB - UFT is given to the patients with digestive cancer from the time before operation to prevent intra- and post-operative cancer dissemination and metastases. UFT (400 mg/day in terms of tegafur) was given preoperatively for 1-6 days in 6 patients with gastric cancer and 13 with colorectal cancer. The interval between the last administration and the beginning of the operation was 3.9 +/- 1.5 hours (mean +/- SD). The concentrations of tegafur, 5-FU, and uracil in the blood collected at the time of tumor resection were 9.68, 0.017, and 0.08 microgram/ml, respectively. In the patients with gastric cancer 5-FU concentration was 5.5 times higher in the normal mucosa, 3.3 times in lymph nodes, and 10.7 times in the tumor tissues than in the blood. In colorectal cancer patients, also, the 5 FU concentration was 5.6, 8.3 and 20.8 times higher in the normal mucosa, lymph nodes, and the tumor tissue, respectively, than in the blood. The 5-FU concentration in gastric cancer and colorectal cancer tissues decreased with time after administration of UFT but remained above the effective concentration 1.5-7 hours after administration of 200 mg. The tissue concentrations of FT-207, uracil, and 5-FU were correlated with each other. PMID- 1444484 TI - [Blood concentrations of futraful, uracil and 5-fluorouracil (5-FU) after UFT administration in the various reconstructions after gastrectomy. Saitama UFT Research Group]. AB - The study was undertaken in the total of 58 gastric cancer patients among which 17 of Billroth (BI), 14 of Billroth II (B II) anastomosis after subtotal gastrectomy, and 7 of jejunal interposition, 9 of double tract and 11 of Roux en Y anastomosis after total gastrectomy were included. Blood samples were taken before 200 mg of per oral UFT administration and after 1, 2, 3, 5 and 7hrs. consecutively. The blood Futraful (FT) level in the total gastrectomy groups reached peak concentration within 1hr and kept in relatively high level during the observation period of 7hrs. The time to maximum FT concentration delayed in almost of B I and a few of B II patients. The concentration curves of uracil (URA) and 5-FU were similar in shape, revealing steep increase and decrease except B I anastomosis which showed gentle course. The plotted maximum concentrations of URA and 5-FU in the every type of reconstruction showed a significant correlation in the regression line. In the analysis of AUC, URA/FT was under 10%, suggesting the longer retention of the unmetabolite type of FT and early disappearance of URA. The ratio of 5-FU/FT was indifferent in each reconstruction. 5-FU/URA was higher in subtotal rather than total gastrectomy groups. From the data obtained, blood concentration of 5-FU after UFT administration was considered to depend on the emptying status in the gastrectomies. And moreover, it depended on blood URA level, since FT from which 5-FU was derived, was kept still sufficiently remained during observation period. PMID- 1444485 TI - [A study of urinary tegafur, 5-fluorouracil (5-FU) and uracil concentrations in the cases of gastric carcinoma for the confirmation of drug-taking compliance after UFT oral administration]. AB - We have measured urinary tegafur (FT), 5-FU and uracil concentrations after UFT oral administration (300 mg daily for 7 days) to confirm drug-taking compliance in the 17 cases undergone gastrectomy. Urinary FT and 5-FU concentrations reached to the plateau 2 and 3 days after administration, respectively, and were maintained until the day after termination of administration. Subsequently, FT and 5-FU concentrations also decreased about 50% at 2 day, 20% at 3 day, 10% of the plateau values at 4 day after termination, respectively. The mean plateau value of urinary FT was 12.9 +/- 6.8 micrograms/dl, and that of urinary 5-FU was 0.67 +/- 0.50 microgram/dl. On the other hand, uracil concentration, was not different before and after administration because of the uracil being present endogenously. Therefore, it was suggested that measurement of urinary FT and 5-FU concentrations is useful for confirmation of UFT-taking compliance. PMID- 1444486 TI - [Intraperitoneal administration of cisplatin (CDDP) for advanced or recurrent gastric cancer with peritoneal dissemination]. AB - This study was undertaken in order to evaluate the effect of intraperitoneal administration of CDDP on fourteen patients with peritoneal dissemination of advanced or recurrent gastric cancer. The procedure was used together specific hydration transfusion and diuretics. Two patients showed a complete response and 5 patients a partial response. Following this therapy, 2 patients have survived for more than 6 months. Alimentary symptoms (nausea, vomiting) were found but renal toxicity and serious myelosuppression were not recognized in all patients. PMID- 1444487 TI - [Clinical evaluation of intra-arterial methotrexate, vinblastine, doxorubicin and cis-platinum for bladder cancer]. AB - Chemotherapy regimens including Methotrexate, Vinblastine. Doxorubicin and Cis platinum (M-VAC) have shown objective responses in more than 50% of uroepithelial tumors. And intra-arterial chemotherapy can theoretically increase the drug concentration delivered to the tumor with maximum efficacy and less toxicity. In this report we review our experience at Matsuyama Red Cross Hospital between September 1987 and February 1991 using intra-arterial M-VAC in 21 evaluable patients with bladder cancer. Response was observed in 62% of the treated patients, two with complete remission and eleven with partial remission. WBC nadir and platelet nadir were mild to moderate. Other adverse effects such as mucositis, hair loss and creatinine elevation were seen in a small number of patients. Intra-arterial M-VAC can be one of the most useful forms of chemotherapy for patients with bladder cancer. PMID- 1444488 TI - [Maintenance chemotherapy using UFT and FT for gynecological malignant tumors. The Gunma Prefectural Society for Study of Chemotherapy for Gynecological Cancer]. AB - The Gunma Prefectural Society for Study of Chemotherapy for Gynecological Cancer made a comparative study on postoperative supplementary chemotherapy including UFT and FT-E for gynecological malignant tumors. The number of cases registered totaled 182, which was broken down into ovarian cancer 53 cases, uterine cervical cancer 89 cases and endometrial cancer 30 cases. Complete cases among them consisted of ovarian cancer 53 cases, uterine cervical cancer 86 cases and endometrial cancer 27 cases for a total of 166 cases. Ovarian cancer was stratified into the completely and incompletely removed cases, uterine cervical cancer into postoperative non-irradiated and irradiated cases and endometrial cancer into the positive metastasis (+) group and negative metastasis (-) group. Then the UFT administration group and FT-E administration group were compared for postoperative survival. There were control groups for both ovarian and endometrial cancer. UFT administration showed a significant improvement in the survival rate (P < 0.05) compared to the FT-E administration group in the cases of ovarian cancer completely removed and the cases of endometrial cancer irradiated after operation. No significant difference was observed between other groups compared. The incidence of side effects was 20.6% (20/97) in the UFT administration group and 3.6% (2/55) in the FT-E group. Neither group showed any serious side effects. PMID- 1444489 TI - [PMUE therapy (CDDP, MMC, UFT, etoposide) for advanced gastric cancer--a case report]. AB - CDDP, MMC, UFT and Etoposide (PMUE)-combined therapy was given to a 62-year-old man with advanced gastric carcinoma. PMUE therapy consists of i.v. injection of CDDP 75 mg/m2 and MMC 10 mg/body on day 1, i.v. injection of Etoposide 50 mg/body on days 3, 4 and 5 and consecutive daily administration of UFT 400 mg/body, with 3 weeks as one course. He was admitted for Borrmann type 3 gastric carcinoma with multiple liver metastasis, lymph node metastases and peritoneal dissemination, the underwent total gastrectomy with R2 lymph node dissection. He was treated four times with this therapy after sensitivity test for carcinostatic agents (SDI test), which resulted in complete remission, as confirmed by CT scan and second look operation. The patient has currently been free of disease, and we conclude that this PMUE therapy is extremely effective for advanced gastric carcinoma. PMID- 1444490 TI - [A case of gastric cancer with multiple liver metastases effectively treated with PMUE (CDDP, MMC, UFT, etoposide) hepatic arterial chemotherapy]. AB - A 62-year-old male patient with progressive gastric cancer and multiple liver metastases (H3, P0, ss gamma, n4) underwent total gastrectomy (R1). After 2 years and 2 months, he was re-hospitalized with epigastric tumor caused by re manifestation of liver metastasis as well as inappetence. Since a large focus of liver metastasis and intraportal tumor embolism was identified, a continuous intraarterial infusion tube utilizing Infuse-A-Port was inserted in the hepatic artery. After conducting 2 cycles of PMUE intra-arterial chemotherapy, the tumor size was reduced by 84% (PR); and CEA, which had been high upon rehospitalization, recovered to the normal level. After discharge, the patient has been receiving 5-FU arterial infusion as an outpatient and undergoing UFT oral chemotherapy. The efficacy has continued and he has been well for 3 years since operation. Often operations for gastric cancer accompanied with multiple liver metastasis meet with little success, and almost no case of prolonged survival has been reported. In this case, the effectiveness of PMUE arterial infusion chemotherapy was clear, the patient has been well for 3 years since operation, and is an interesting example with seemingly good prospects for long survival. PMID- 1444491 TI - [A five-year-survival case in which complete response was recognized after combined chemotherapy using 5-fluorouracil, adriamycin and mitomycin C (FAM) for unresectable gastric cancer]. AB - FAM (5-fluorouracil, adriamycin, mitomycin C) therapy was performed on a 65-year old man with unresectable gastric cancer. Cancer cells have not been recognized by endoscopic biopsy after the patient's complete response. He is alive without metastasis of recurrence for five years. PMID- 1444492 TI - [Two cases of pulmonary metastasis of colorectal cancer successfully treated with oral 5'-DFUR]. AB - Two patients with pulmonary metastasis of colorectal cancer, who had previously undergone radical resection of primary tumor, were orally administered 5'-DFUR at 1,200 mg per day. Complete responses were obtained in both. The duration of response was 42 and 13 weeks, respectively. Some side effects such as diarrhea and aguesia were found in each patient, but the treatment could be continued after temporary suspension for a while or by decreasing the dosage. We concluded that pulmonary metastasis of colorectal cancer can respond remarkably to oral administration of 5'-DFUR at 1,200 mg per day, if the tumor cells have sensitivity to this drug. PMID- 1444493 TI - [A case report of bone metastasis diagnosed by MRI and effectively treated with UFT after breast conserving therapy for breast cancer]. AB - A 66-year-old woman with left breast cancer (medullary carcinoma; T1cN1M0; Stage II A) was treated with breast conserving therapy combined with lumpectomy, radiotherapy, chemotherapy and endocrine therapy beginning in March, 1990. She complained of back pain and was diagnosed as having bone metastasis to the lower thoracic spine by bone scintigram and MRI examination in September, 1990. Oral administration of UFT (300 mg/day) was started, and 5 months later, back pain disappeared; nineteen months later, no definite findings of bone metastasis were observed on bone scintigram and MRI. It was concluded that long-term oral administration of UFT is an effective remedy for bone metastasis after breast conserving therapy for breast cancer. PMID- 1444494 TI - [A case of advanced breast cancer with multiple organ metastases successfully treated by tamoxifen]. AB - A 66-year-old postmenopausal woman presented in June 1991 with a giant ulcerated left breast tumor. She had discovered the tumor two years previously, but had never visited any medical institution. She was diagnosed as advanced breast cancer with multiple lung metastases, bone metastasis, and both supraclavicular lymph node metastases by physical examination, fine needle aspiration cytology, chest X-P, and bone scintigraphy. Incisional biopsy, performed to confirm the histological type of breast cancer and to evaluate estrogen and progesterone receptor (ER and PgR) status, revealed solid-tubular carcinoma. Both ER and PgR were highly positive at 322.6 and 228.0 fmol/mg protein, respectively. Therefore, endocrine therapy was chosen to treat this advanced breast cancer patient, although she had multiple organ metastases. Twenty mg of Tamoxifen a day was administered per os. After treatment with tamoxifen, the size of ulceration started to decreased and the dyspnea caused by multiple lung metastases was reduced. Eight weeks after, she showed partial response (PR) determined from the size of the ulceration and chest X-P. She has been maintaining PR for more than 9 months. Thus, Tamoxifen was shown to be very effective for this case of advanced breast cancer with multiple organ metastases. PMID- 1444495 TI - [A case of jejunal vein thrombosis due to medroxyprogesterone acetate]. AB - The patient was a 68-year-old woman with advanced breast cancer which had been treated by modified radical mastectomy two years and nine months earlier. After the surgery, tamoxifen citrate (TAM) was orally administered in addition to various types of chemotherapy. Because the patient complained of nausea and weight loss, medroxyprogesterone acetate (MPA) was orally administered instead of TAM. The patient complained of intense abdominal pain on the 35th day of administration. Laparotomy was then performed for her acute abdominal problem. Because necrosis from bleeding due to jejunal vein thrombosis was observed in the jejunum for about 15 cm, resection of the jejunum was carried out. Histological observation demonstrated thrombosis in the vein, and cellular infiltration around the thrombosis. The postoperative prognosis has been favorable and the postoperative course is now being monitored at our clinic (2 months after surgery). The patient has no complications such as diabetes mellitus or hypercholesterolemia. The thrombosis observed in the jejunal vein, which is a rare site for it on the 35th day of MPA administration was induced by MPA. Due attention must be paid to the formation of thrombosis when using MPA. PMID- 1444496 TI - [Production of bone resorption stimulating factor by adult T-cell leukemia cells]. PMID- 1444497 TI - [Comparative changes in hepatic function induced by transhepatic arterial chemoimmunoembolization among liver cancer patients]. PMID- 1444498 TI - [Hydrea, an effective drug for chronic myelogenous leukemia]. AB - Hydroxycarbamide (the brand name: Hydrea) was found effective to chronic myelogenous leukemia (CML) in Japan. In the preclinical study, this compound was active against mouse leukemia L 1210 and inhibited DNA synthesis. Clinically, Hydrea was given orally at the daily dose of 500-2,000 mg, dividing 1-3 times. For the maintenance therapy after remission induction, daily dose of 500-1,000 mg was given, dividing 1-2 times. As for the side effects, myelosuppression, disturbance of the gastro-intestinal tract and temporal liver and renal dysfunctions were observed. The response rate in the remission-induction therapy was as high as 92.1%. PMID- 1444499 TI - Pemphigus foliaceus. Use of antimalarial agents as adjuvant therapy. PMID- 1444500 TI - Systemic steroids with or without 2% topical minoxidil in the treatment of alopecia areata. AB - BACKGROUND AND DESIGN: Thirty-two patients with mild to extensive alopecia areata, including 16 patients with alopecia totalis or universalis, entered a randomized, controlled trial of a 6-week taper of prednisone followed by either 2% topical minoxidil or vehicle applied three times daily for an additional 14 weeks. The results of this study were compared with an open trial of 48 patients with alopecia areata treated with a similar taper of prednisone with concomitant 2% topical minoxidil applied twice daily. Only terminal hair growth was considered and was quantitated as 1% to 24%, 25% to 49%, 50% to 74%, and 75% to 100%: only those with more than 25% terminal hair regrowth were considered to have had an objective response. RESULTS: At the end of 6 weeks of prednisone, 47% (15/32) of patients had more than 25% regrowth, including nine of 20 patients who had had at least 75% hair loss at baseline. Side effects of prednisone were primarily weight gain and mood changes/emotional lability. At 3 months, six of seven minoxidil-treated patients vs one of six vehicle-treated patients who had an objective response to prednisone maintained or augmented this hair growth: at the 20-week visit, these numbers were three of seven and zero of four patients, respectively. In the open trial, objective hair growth with prednisone was 30%, related to the extent of hair loss at baseline, and this growth persisted in more than 50% of patients at 6 months with the use of 2% topical minoxidil. CONCLUSIONS: A 6-week taper of prednisone offers potential for more than 25% regrowth in 30% to 47% of patients with alopecia areata with predictable and transient side effects. Two percent topical minoxidil three times daily appears to help limit poststeroid hair loss. PMID- 1444501 TI - Serologic markers of gluten-sensitive enteropathy in bullous diseases. AB - BACKGROUND AND DESIGN: Dermatitis herpetiformis (DH) is characterized immunologically by the presence of IgA immune deposits in the skin and by the presence of various serum antibodies. Of these, antibodies to gliadin, reticulin, and endomysium have been found to be significant. There are, however, conflicting reports as to the exact specificity and sensitivity of these serologic markers in diagnosing DH. We examined the disease specificity of these three antibody markers in 14 patients with DH, in 98 patients with pemphigus and pemphigoid, and in 26 normal subjects. Reticulin and endomysium antibodies were detected by indirect immunofluorescence and gliadin antibodies by means of the enzyme-linked immunosorbent assay method. RESULTS: Among the various bullous diseases, endomysial and reticulin antibodies were found to be disease specific for DH. Endomysial antibodies occurred in twice the number of DH patients (72%) compared with the occurrence of reticulin antibodies (36%). Antigliadin antibodies were detected in two thirds of DH patients and were not disease specific since increased frequencies of these antibodies were also detected in patients with pemphigus and pemphigoid. CONCLUSION: These studies support the earlier findings of the high degree of specificity of endomysial antibodies for DH and, thus, help to differentiate DH from other bullous disorders. PMID- 1444502 TI - Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa 2b therapy. AB - BACKGROUND AND DESIGN: Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS: Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS: This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result. PMID- 1444503 TI - U1RNP antibody-positive neonatal lupus. A report of two cases with immunogenetic studies. AB - BACKGROUND: Neonatal lupus erythematosus (NLE) is a distinct subset of lupus characterized by cutaneous findings (50%), cardiac conduction defects (50%), and autoantibodies to Ro (SS-A) antigen. HLA typing studies of Ro (SS-A) antibody positive mothers of infants with NLE have shown an association with the HLA-DR3 phenotype. We report the clinical and serologic features of two infant-mother pairs who are U1RNP antibody positive and Ro (SS-A) antibody negative. HLA typing is reported on these infants, their mothers, and two additional infant-mother pairs with U1RNP antibody-positive lupus whose clinical features have been reported previously. OBSERVATIONS: Cutaneous findings included malar erythema, annular and polycyclic plaques, and scales that resolved with residual telangiectasia and hyperpigmentation 6 months after birth. Systemic abnormalities, including complete heart block, were absent. HLA typing revealed HLA-DR3 in two of four mothers, HLA-DR4 and HLA-DRw53 in two of four mothers, and either HLA-DQ1 or HLA-DQ3 in four of four mothers. No distinct HLA associations were seen in the three infants examined. CONCLUSIONS: The spectrum of cutaneous disease in U1RNP antibody-positive infants is similar to Ro (SS-A) antibody positive infants with NLE. Complete heart block was not a feature of U1RNP antibody-positive NLE. HLA typing studies show a more diverse immunogenetic pattern in U1RNP antibody-positive mothers of infants with NLE compared with Ro (SS-A) antibody-positive mothers. PMID- 1444504 TI - Vesicular erythema migrans. AB - BACKGROUND: Lyme disease is the most common vector-borne disease in the United States. The characteristic rash, erythema migrans, is an early sign of the disease. Clinical criteria remain the "gold standard" for diagnosis at this stage of illness. OBSERVATIONS: Five (8%) of 65 patients with erythema migrans seen in a Lyme disease diagnostic center in Westchester County, New York, had a lesion with vesicles. Borrelia burgdorferi was cultured from two of five. In one case the positive culture came from a swab of the blister fluid. CONCLUSIONS: Recognition of erythema migrans and its variants is important, since early treatment of Lyme disease may prevent late complications. Vesicular erythema migrans should be added to the differential diagnosis of inflammatory vesicular rashes in the appropriate clinical setting. PMID- 1444505 TI - Two cases of transfusion-associated graft-vs-host disease after open heart surgery. AB - BACKGROUND: Some cases of blood transfusion-associated (TA) graft-vs-host disease (GVHD) in immunocompetent patients have been reported, but those dermatologic findings were not precisely mentioned. We describe patients with clinicopathologically TA-GVHD and compare TA-GVHD and acute GVHD after bone marrow transplantation. OBSERVATIONS: Two cases of TA-GVHD after open heart surgery are reported. In both immunocompetent patients, severe erythema multiformelike skin rash developed over the entire body, followed by fever, diarrhea, jaundice, transaminitis, pancytopenia, and marrow alpasia approximately 10 days after operation. The rash in one patient changed from erythema multiformelike to toxic epidermal necrolysis at death. Skin biopsy specimens revealed eosinophilic bodies, basal vacuolation, and exocytosis in the epidermis. Eosinophilic bodies tend to appear in the upper epidermis. Immunohistochemistry studies revealed that infiltrating cells were CD4 and CD8. While acute GVHD in immunosuppressed patients who have undergone bone marrow transplantations often shows lichenoid histologic features, TA-GVHD in our patients who were immunocompetent may resemble severe erythema multiforme or toxic epidermal necrolysis. The difference in TA-GVHD may be related to lack of host modification by immunosuppression. CONCLUSIONS: Irradiation of the blood products should be required in open heart surgery, for TA-GVHD in immunocompetent patients is almost always fatal. PMID- 1444506 TI - Dermatology in France. PMID- 1444507 TI - Immune dysregulation in atopic eczema. AB - BACKGROUND: In this review, present knowledge of atopic eczema immunopathogenesis is summarized, emphasizing recent new findings. Systemic abnormalities in cell mediated immunity have not been demonstrated firmly in patients with atopic eczema. Within the skin itself, there is evidence for decreased cell-mediated immunity, which is partially correlated with the severity of skin disease. Atopic eczema, however, cannot be regarded as a direct result of decreased cutaneous cell-mediated immunity, since immunophenotyping studies have revealed activated T cells as well as dendritic cells within involved skin. In addition, disease marker studies in peripheral blood indicate vigorous T-cell activation in atopic dermatitis. OBSERVATIONS: The original observation of IgE molecules on the membranes of Langerhans cells may indicate trapping of IgE allergen complexes, their processing, and subsequent presentation to allergen-specific T cells within involved skin. Recent findings as to the abnormal regulation of IgE synthesis in atopy point to a preferential expansion of interleukin 4 and interleukin 5 producing allergen-specific T cells, leading to increased production of interleukin 4 and thus increased levels of allergen-specific IgE. We have prepared atopic skin as well as peripheral blood-derived T-cell clones and determined their specificity and cytokine production profile. Results indicate in situ production of interleukin 4 and interleukin 5 within involved skin in response to environmental antigens. CONCLUSIONS: These new findings as to the basis of IgE dysregulation in atopy, as well as to the identification of an abnormal cytokine secretion pattern by T cells presumed to be central in immunopathogenesis of atopy-related disorders, suggest a distorted and cytokine mediated self-perpetuating response of the skin immune system to environmental allergen(s) in the pathogenesis of skin disease in atopy. These observations may have important implications for the development of new therapies for atopic eczema. PMID- 1444508 TI - Photoallergic contact dermatitis. Results of photopatch testing in New York, 1985 to 1990. AB - BACKGROUND: Over a 6-year period, 187 patients with a history of photosensitivity were photopatch tested using standard techniques. Seventy-six patients were male and 111 were female. Most patients were white (151 patients). Two thirds of the patients were between the ages of 31 and 60 years. OBSERVATION: Testing revealed a total of 63 positive reactions: 14 plain contact, 41 photocontact, and eight combined contact and photocontact in 37 (20%) patients. Careful history taking resulted in a diagnosis of clinically relevant photoallergic contact dermatitis in 54% of these 37 patients or 11% (20) of the total tested. Ten of the relevant responses were due to fragrance ingredients (musk ambrette and 6-methylcoumarin); 18 were due to sunscreen agents (nine to p-aminobenzoic acid and esters, nine to oxybenzone). The fragrance reactions occurred in the early years of the study (1985, 1986, and 1987) while the sunscreen agents accounted for all but two of the 14 positive reactions in the last 3 years of the study (1988, 1989, and 1990). CONCLUSION: These data suggest that the incidence of photoallergy due to fragrances is declining, while reactions to sunscreen agents, in particular oxybenzone, are increasing. This trend may reflect an altered use pattern by the general population for products containing these chemicals. PMID- 1444509 TI - Alopecia areata. A review of therapy, efficacy, safety, and mechanism. AB - Although it is clear from the foregoing that some of the drugs and chemicals used to treat severe alopecia areata are efficacious to some degree, it is impossible to draw any meaningful comparisons among the data outlined in Tables 1 and 2. Virtually all of the studies were designed differently. Differences in chronicity and extent of disease as well as history of previous treatment resistance may significantly affect efficacy data even as two investigators compare the same drug. Drug-induced hair regrowth in alopecia areata may be very slow; a cosmetic response may take 1 to 2 years to achieve. Efficacy determinations made at shorter intervals may, therefore, not reflect true therapeutic potential. Efficacy end points vary significantly and need to be standardized. From a practical standpoint, scalp hair coverage that is deemed by the patient to be cosmetically acceptable seems to be a reasonable efficacy end point to report. Maintenance of cosmetic effect with continued treatment and/or following discontinuation of treatment also is useful to document. Table 3 outlines my approach to therapy of alopecia areata. Topical treatments often must be used for as long as 3 months before evidence of regrowth can be seen. In my experience with severe disease, if topical treatments cannot control a flare or induce regrowth, then the patient will often require either lengthy or frequent courses of systemic steroids. In my experience, prednisone doses as low as 20 mg/d may be associated with aseptic neurosis of the hip or severe gastrointestinal bleeding. Severe alopecia areata is a disease for which all therapies are, at best, palliative and, at worst, potentially harmful to patients who are usually otherwise very healthy. The psychosocial significance of this disease is enormous. The insights shared by a long-time sufferer of the disease mirror those expressed by the many patients with whom I have worked during the past 12 years. Three key elements to effectively treat the patient are (1) to help the patient understand the disease; (2) to encourage the patient to share his or her feelings with the physician, family, friends, and other sufferers of the disease; and (3) to help the patient to maintain a sense of hope for future scientific knowledge and treatment of the disease. With a thorough knowledge of the potential benefits and risks of each treatment or combination treatment, the physician with the patient's understanding and cooperation may then embark on what may be in severe cases a lengthy and sometimes unproductive therapeutic process. PMID- 1444510 TI - Symmetrical retroauricular papules. Basal cell carcinoma. PMID- 1444511 TI - Multiple red nodules on lower abdomen. Metastatic carcinoma of the prostate. PMID- 1444512 TI - The subtleties of Mohs surgery. PMID- 1444513 TI - Redefinition of Mohs surgery. PMID- 1444514 TI - Topical cyclosporine in the treatment of vulvar lichen sclerosus: clinical, histologic, and immunohistochemical findings. PMID- 1444515 TI - Congenital trichoid keratosis of the scalp. PMID- 1444516 TI - Toxic epidermal necrolysis after hepatic transplantation. PMID- 1444517 TI - Parity, polypregnancy, paternity, and PUPPP. PMID- 1444518 TI - Hair casts: a clinical and morphologic control study. PMID- 1444519 TI - Drug abuse in children and adolescents: an update. PMID- 1444520 TI - Consent to treatment in childhood. PMID- 1444521 TI - Molluscum contagiosum. PMID- 1444522 TI - Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants. AB - A randomised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1, proteins induced by vitamin K absence (PIVKA-II), and clotting factors. Two groups of about 165 healthy breast fed infants who received at random 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age. Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group, blood coagulability, activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups. At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable. At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5% of infants. Therefore, a repeated oral prophylaxis will be necessary to completely prevent (biochemical) vitamin K deficiency beyond the age of 1 month. PMID- 1444523 TI - Oscillations of body temperature at night. AB - There is increasing evidence that overheating is a contributing factor for some cot deaths. One hypothesis is that infant thermoregulation is closely related to respiratory control. To test this hypothesis it was necessary to determine the normal pattern of body temperature in the developing infant. A system has been designed and built to record continuously temperature signals from ambient, rectal, and various skin site sensors. Overnight studies were performed on 30 infants aged between 2 and 26 weeks in a hospital ward. Various time and frequency domain analyses of the temperature data have been developed. Analysis of body temperature rhythms has confirmed patterns during sleep which mature with age. In addition a periodic oscillation of body temperature has been found with a cycle of approximately one hour. This oscillation may reflect sleep state and its further study may give an insight into control of infant thermoregulation and the integration of this control with that of breathing and the cardiovascular system. PMID- 1444524 TI - Factors affecting the development of night time temperature rhythms. AB - The rectal temperature of 26 infants between 6 and 16 weeks old was monitored continuously for one night each week. Rectal temperature always decreased with sleep but the minimum temperature attained changed with age. Some time between 8 and 16 weeks old the minimum sleeping rectal temperature decreased abruptly from around 36.8 degrees C to around 36.4 degrees C. This change was complete within one week and did not normally revert unless the infant became ill. Some infants changed as early as 8 weeks old, others not until 16 weeks. Breast fed infants changed significantly earlier than bottle fed infants. Girls changed significantly earlier than boys. First born infants changed significantly earlier than second or subsequent infants. Early changes were significantly more likely to be sleeping lateral or supine, and to have older mothers. They tended to come from more affluent families. There was no association between the time of change and the thermal environment in which the infant slept or the number of episodes of minor illness in the early weeks of life. PMID- 1444525 TI - Paediatric cardiac transplantation with steroid-sparing maintenance immunosuppression. AB - In order to determine the results of steroid-sparing maintenance immunosuppression in paediatric patients who have undergone orthotopic heart transplantation (OHT), a retrospective study was undertaken in 12 children and five infants (median age 3.5 years). Preoperative diagnoses were cardiomyopathy in seven and congenital heart disease in 10 patients. Immunosuppression was induced by cyclosporin, azathioprine, methylprednisolone, and antihuman lymphocyte immune globulin. It was maintained with cyclosporin and azathioprine. After induction, five patients received no further steroids. The remainder, except one, required only pulses for rejection (13 episodes or 0.51 episodes/patient year). Long term complications included hypertension in six, and renal impairment in three children. There were no early or late deaths from infection. Actuarial survival was 94% at one year. Of the children followed up for more than one year, all demonstrated an increase in height SD scores (mean (SD) -2.15 (1.35) to -1.15 (1.16)). We conclude that a steroid-sparing maintenance immunosuppression regimen can be successfully employed in paediatric OHT, and that significant catch-up growth can be achieved postoperatively. PMID- 1444526 TI - Intravenous immunoglobulin in HIV-I infected haemophilic patients. AB - In order to evaluate the efficacy of intravenous immunoglobulin (IVIG) in the early stages of HIV infection (patients without AIDS or AIDS related complex) a prospective controlled open trial was conducted in 36 patients (age 6-19 years) with haemophilia. Eighteen patients received 0.3 g/kg IVIG at two week intervals; 18 patients served as controls. Major criteria for the evaluation were progression of HIV disease assessed by the modified Brodt/Helm classification, number of infectious events and HIV associated thrombocytopenia, and the CD4+ T cell count. After 24 months of evaluation seven patients in the IVIG group and five patients in the control group deteriorated according to their staging, with one patient in each group developing AIDS. Thrombocytopenia and infectious events, but no severe bacterial infections, occurred in both groups in similar numbers. The absolute CD4+ T cell count decreased by 284/microliters in the IVIG group and by 143/microliters in the control group respectively (mean values). The statistical analysis of these criteria did not reveal any significant difference. In conclusion, IVIG was not effective in the early stages of HIV infection in patients with haemophilia. IVIG did not slow down the progression of HIV disease and did not prevent the development of an immunodeficiency as assessed by the CD4+ T cell count. PMID- 1444527 TI - Gastrointestinal complications of gastrocystoplasty. AB - The cases are reported of five children with chronic renal failure who underwent gastrocystoplasty for a variety of urological disorders. Gastrocystoplasty comprises the transplantation of a vascularised segment of stomach to the bladder to form an augmented neobladder. The patients had gastrointestinal complications after the operation, including considerable weight loss in all five patients, accompanied by marked failure to thrive in four of the five patients, and food aversion, feeding intolerance, dumping syndrome, delayed gastric emptying, and oesophagitis in two patients. Three of the five patients developed severe abdominal pain and haemorrhagic cystitis secondary to gastric acid secretion in the neobladder from the transplanted gastric pedicle. Nutritional and pharmacological interventions were used to manage the gastrointestinal problems. Explanations are offered for the pathophysiology of the observed complications of gastrocystoplasty. It is believed that the use of this procedure in infants and children, particularly those with chronic renal failure and uraemia, warrants caution until successful long term follow up and experience with this procedure have been reported. PMID- 1444528 TI - Prepubertal height velocity references over a wide age range. AB - In order to correct height velocities for the confounders age and sex, SD scores can be calculated using the mean and the SD of the height velocity in the normal population. However, current methods are inappropriate for prepubertal children in the age range in which puberty occurs, because reference groups then consist of a mixed prepubertal/pubertal population. The mathematical infancy-childhood puberty (ICP) model opens up the possibility of dissecting the puberty component from the total growth curve. New references for height velocity for prepubertal children calculated over a 12 month interval up to the ages of 15.5 years (boys) and 13.5 years (girls) have been constructed on the basis of adaptations of the ICP model and the Swedish longitudinal growth study. PMID- 1444530 TI - Centiles for adult head circumference. AB - Reference range for head circumference on the Tanner charts do not go beyond age 16. In this study the head circumference and heights of 354 adults in two British centres were measured. The centile charts constructed from these measurements show that adult head circumference is related to height. The mean head circumference of a male of average height is above the 97th centile for a 16 year old on the Tanner charts. The paediatric charts are therefore inappropriate for use in adult males. PMID- 1444529 TI - Bone age, social deprivation, and single parent families. AB - It is well known that deprivation affects bone growth. The study was set up to investigate what aspects of deprivation are of greatest importance. Bone ages of 1593 child trauma patients aged 0-19 years from Middlesbrough General Hospital, Cleveland, were related to local authority ward indices of socioeconomic status (51 wards). After adjustment for chronological age and sex, the mean bone ages in each ward were highly significantly negatively associated with five ward indices of deprivation: the rate of single parent families, low care ownership, unemployment, rented housing, and overcrowding. There was a mean four month deficit in bone age among children living in wards with the highest single parent family rates. The inverse association between deprivation and bone age is unlikely to be causal throughout childhood, as older and younger children were affected to the same extent. However the bone age deficit could be caused by deprivation retarding skeletal maturation during a critical period in early life. PMID- 1444531 TI - Immunisation status in inner London primary schools. AB - In one inner London district health authority, the immunisation status of children attending their routine school entry health interview was reviewed over four terms. During the course of these interviews, school nurses completed a questionnaire with parents that asked for their child's immunisation history and details of family and social background. Parental reporting of immunisation history was compared with district health authority records. Only 56% of children reviewed were found to be fully immunised, although a substantial number (386) of the 513 partially immunised children required only a preschool booster. Four percent (54) of the children had received no immunisations; a disproportionately high number of these were recent immigrants. Mechanisms for identifying unimmunised children before they enter communal groups need to be established. PMID- 1444532 TI - An audit of preschool vision screening. AB - An audit was carried out to clarify the dispute surrounding the vision screening test at 3.5 years. The uptake was 53.5%, sensitivity 77%, specificity 96%, and positive predictive value 50%. In particular the uptake was poor and the test needed a clear policy for the future. PMID- 1444533 TI - Microfollicular thyroid adenoma and congenital goitrous hypothyroidism. AB - Three patients with congenital goitrous hypothyroidism are reported. They were treated with adequate thyroxine replacement and developed well defined microfollicular thyroid adenomas despite being euthyroid clinically and biochemically throughout their clinical course. Patients with congenital goitrous hypothyroidism appear to be at increased risk of developing thyroid adenoma in childhood despite the use of replacement thyroxine treatment in physiological doses. PMID- 1444534 TI - Oral hairy leukoplakia in vertically and horizontally acquired HIV infection. PMID- 1444535 TI - Building a combined child health service. PMID- 1444536 TI - Consultative work in child and adolescent psychiatry. PMID- 1444537 TI - Statistics from the inside. 7. Regression and correlation. PMID- 1444538 TI - Recent advances in understanding muscular dystrophy. PMID- 1444539 TI - Investigation of metabolic disorders resembling Reye's syndrome. AB - Ten per cent of patients initially reported with Reye's syndrome in the British Isles (1981-91) were subsequently found to have an underlying inherited metabolic disorder (IMD). There was also evidence to suggest that other cases may not have been recognised. The range of metabolic disorders that mimic Reye's syndrome is wide and specialist, often complex, investigations are required to make a specific diagnosis. Those patients presenting with Reye's syndrome-like illness but also with one or more clinical features suggestive of an IMD require particular attention and detailed investigation. Recommendations for specimen collection and investigation are presented. PMID- 1444540 TI - Relationship between urinary and serum growth hormone and pubertal status. PMID- 1444541 TI - Malnutrition in children with cancer. PMID- 1444542 TI - Intravenous volume replacement: which fluid and why? PMID- 1444543 TI - Pediatrics in the accident and emergency department. PMID- 1444544 TI - Herpes simplex virus infection in pregnancy. PMID- 1444545 TI - Kidney function in the very low birthweight infant. PMID- 1444546 TI - Renal function in sick very low birthweight infants: 1. Glomerular filtration rate. AB - A total of 135 measurements of polyfructoside clearance as a measure of glomerular filtration rate (GFR) were made in 39 infants of 25.5-33 weeks' gestation, birth weight 720-2000 g, between the ages of 0.5 and 33 days. GRF was related to postconceptional age and increased exponentially from geometric mean 0.59 ml/min at 26 weeks' postconceptional age to 1.40 ml/min at 33 weeks. GFR in the first week and GFR at later ages were the same for a given postconceptional age. GFR was the same in sick infants with severe ventilatory failure as in less ill infants. There was no evidence that GFR was influenced by nitrogen input. GFR increases postnatally in a preprogrammed way irrespective of other postnatal events. When factored by body weight GFR in the first week increased only little from arithmetic mean 0.70 ml/min/kg at 26 weeks to 0.84 ml/min/kg at 33 weeks, but older infants often had a falsely high GFR per kg when they lost weight in the first week or two after birth or failed to gain weight later. PMID- 1444547 TI - Renal function in sick very low birthweight infants: 2. Urea and creatinine excretion. AB - Plasma urea and creatinine concentrations and urea and creatinine clearances and excretion were measured in a sample of 40 infants of 25.5-33 weeks' gestation, birth weight 720-2000 g, between the ages of 0.5 and 33 days. Creatinine excretion rate was between 60 and 120 mumol/kg/day in the first five postnatal weeks (mean 90.5) and was independent of sex or growth retardation. This can be used in clinical practice to estimate instantaneous urine flow rate V, if the creatinine concentration is measured in a randomly voided urine sample, from the formula V = 90.5/urine creatinine, with 95% confidence limits +/- 39%. There is a wide range of plasma creatinine at all gestations and ages decreasing from range 75-130 mumol/l in the first two days to 35-80 mumol/l at 3 weeks of age. Plasma urea is a poor indicator of glomerular filtration rate (GFR) in sick preterm infants. GFR (ml/min/kg) can be estimated from plasma creatinine from the formula GFR = 69.2/plasma creatinine but this estimate is imprecise with 95% confidence limits +/- 46%. Urea:creatinine clearance ratio was usually less than 1.0 (range 0.18 to 1.5) and was lower when the urine flow rate was low. Urea excretion was up to 17 mmol/kg/day in the first two weeks, higher in the more immature infants. These high levels were paralleled by a high plasma urea concentration, up to 18 mmol/l. A high plasma urea is not necessarily associated with renal failure or dehydration. PMID- 1444548 TI - Renal function in sick very low birthweight infants: 3. Sodium, potassium, and water excretion. AB - Renal excretion of sodium, water, and potassium was measured on 434 occasions in a sample of 40 infants of 25.5-33 weeks' gestation, birth weight 720-2000 g, between the ages of 0.5 and 36 days. Water excretion varied between 1% and 30% of the glomerular filtration rate, or 15-350 ml/kg/day, and varied widely from day to day in individual infants. Nearly all infants became hyponatraemic before or after the first postnatal week. There were a few instances of hypernatraemia in the first week caused by high insensible water loss. There were high levels of sodium excretion up to 16% of filtered sodium, or 21 mmol/kg/day, in the first two postnatal weeks. Highest levels of sodium excretion were seen in the most immature infants in the first week. In most infants sodium excretion increased either in the first week or later before a subsequent decline. Potassium excretion was often high in the first week, as much as 96% of filtered potassium, or 5 mmol/kg/day, and is associated with early hyperkalaemia. PMID- 1444549 TI - Renal function in sick very low birthweight infants: 4. Glucose excretion. AB - Renal glucose excretion was measured on 239 occasions in a sample of 36 infants of 25.5-33 weeks' gestation, birth weight 720-2000 g, between the ages of 0.5 and 32 days. Glucose was invariably present in urine from the first day. Fractional glucose excretion varied widely from 0.1% to 90% of filtered glucose and glucose excretion rate was up to 15.5 mmol/kg/day and was higher in the most immature infants, especially below 28 weeks' gestation. The highest values were in association with hyperglycaemia between 5 and 15 days but there was no consistent plasma glucose threshold with frequent glucose spillage at normal blood glucose concentrations. There was some correlation with sodium excretion in the first week suggesting that in the absence of hyperglycaemia with a normal filtered glucose load, glucose excretion is caused by proximal tubular immaturity. PMID- 1444550 TI - Simultaneous measurement of preductal and postductal oxygen saturation by pulse oximetry in hyaline membrane disease. AB - Preductal and postductal oxygen saturation were compared in 20 ventilated preterm infants with hyaline membrane disease to establish the frequency of right to left shunting and to assess the accuracy of postductus arteriosus blood gas sampling. One hundred and thirty eight comparisons were made and the frequency of right to left shunting was 17% (95% confidence interval 12 to 25%). Shunting episodes with possible preductal hyperoxia occurred far less commonly on a maximum of 5% of occasions. The findings in infants under 1000 g and of 24-28 weeks' gestation were not significantly different from larger or more mature infants. Shunting occurred significantly more frequently in very ill infants who subsequently died as a result of respiratory disease. PMID- 1444551 TI - Effect of patency of the ductus arteriosus on blood pressure in very preterm infants. AB - Forty one preterm infants (birth weight < 1500 g) were studied by daily Doppler echocardiography for the first week of life to examine the effect of a haemodynamically significant ductus arteriosus (HSDA) on systemic blood pressure. Hourly records of blood pressure were averaged for each infant to produce a 24 hour mean value and the infants were then allocated to groups according to whether, by echocardiographic criteria, there was a HSDA on that day. In infants from 1000 to 1500 g the differences in all parameters of blood pressure between those with and without a HSDA were not significant. In infants < 1000 g the mean blood pressure was significantly less in the infants with a HSDA throughout the first week of life. Systolic blood pressure was reduced by as much as diastolic blood pressure and as a result the pulse pressure did not differ. Infants < 1000 g with a HSDA were given more plasma and a greater number received inotropic support. Gestational age, respiratory disease severity, and complication rates did not differ between those with and without a HSDA. The possibility of a clinically silent HSDA should be considered before large amounts of plasma volume expanders are given to treat hypotension in infants < 1000 g. PMID- 1444552 TI - Annual audit of neonatal morbidity in preterm infants. AB - Annual odds ratios, standardised for known confounding variables, were used to examine trends in major neonatal morbidities among 3220 preterm infants of less than 35 weeks' gestation admitted to a regional referral centre between 1980 and 1991. Despite improved survival, the risk of major cerebral haemorrhage, ventriculoperitoneal shunt insertion, and necrotising enterocolitis was unchanged. A recent reduction in risk of pneumothorax and persistence of the arterial duct was noted. An increased risk for chronic lung disease over time could be accounted for by increased survival, although a similar increase in risk for infection remained unexplained. PMID- 1444553 TI - Prediction of neurodevelopmental outcome in the preterm infant: short latency cortical somatosensory evoked potentials compared with cranial ultrasound. AB - One hundred and twenty six preterm infants, with a gestational age of 34 weeks or less, were studied to compare the predictive value of somatosensory evoked potentials (SEPs) with that of cranial ultrasound. A normal N1 latency was no guarantee of a normal outcome, nor did a persistently delayed N1 latency always correlate with a poor outcome. As a predictor of cerebral palsy, SEPs had a sensitivity of 44% and a specificity of 92%. The presence of a large haemorrhage (grade IIb/III) or cystic leukomalacia on cranial ultrasound predicted cerebral palsy with a sensitivity of 73.6% and a specificity of 83.1%. These results demonstrate that the role of SEPs recorded after median nerve stimulation is limited in preterm infants. PMID- 1444554 TI - Membrane humidification--a new method for humidification of respiratory gases in ventilator treatment of neonates. AB - A humidifier system for neonatology that functions according to the 'membrane humidification' principle was subjected to a performance test in our laboratory. Humidification and heating of the respiratory gases took place in a module consisting of a net of hollow fibres placed inside the incubator. In 18 measurement combinations flow, respiratory gas temperature, and incubator temperature were varied. At respiratory gas temperatures within the range of 33 37 degrees C the minimum international standard for the absolute air humidity in the respiratory gas was achieved or exceeded in all measurements. No controlled clinical tests regarding the importance and long term effects of different temperatures and different humidity levels in the inspiratory air are yet available for the ventilation treatment of neonates. PMID- 1444555 TI - Randomised controlled trial of colloid infusions in hypotensive preterm infants. AB - Colloid infusions are often given to treat hypotension in preterm infants. The aim of this work was to assess whether it was the amount of protein or the volume of the colloid infused which accounted for the observed increase in blood pressure. Sixty preterm infants were randomised (20 in each group) to receive 5 ml/kg 20% albumin, 15 ml/kg fresh frozen plasma, or 15 ml/kg 4.5% albumin. All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids. The infants were randomised when hypotensive (systolic blood pressure less than 40 mm Hg for two hours). There was no significant difference in the blood pressure of the three groups before or one hour after beginning the infusion. The mean increase in blood pressure one hour after completing the infusion, however, was significantly lower in infants receiving 20% albumin: 9% compared with 17% in the group receiving 4.5% albumin, and 19% in the group receiving fresh frozen plasma. It is concluded that the volume infused rather than albumin load is important in producing a sustained increase in blood pressure. PMID- 1444556 TI - Cardiac tumours in intrauterine life. AB - Since 1980, 11 examples of cardiac tumour have been detected in the fetus out of a total of 794 congenital cardiac malformations. Patients were referred because of fetal hydrops in two, a family history of tuberous sclerosis in two, and because of the detection of a tumour mass during a scan at the local hospital in seven. The gestational age range at presentation was from 20-34 weeks. Of eight fetuses where death occurred, the histological type was rhabdomyoma in seven and teratoma in one. In seven cases, the lesion appeared single and in four there were multiple tumours. In two of the cases of rhabdomyoma, other family members had evidence of tuberous sclerosis. Termination of pregnancy took place in four cases; of seven continuing pregnancies, spontaneous intrauterine death occurred in four, and three children are still alive. Two of the three survivors has the clinical picture of tuberous sclerosis. The last case is as yet only 1 month old. In summary, even where the lesion is single, the most likely diagnosis in fetal cardiac tumour is rhabdomyoma, with associated tuberous sclerosis. However, the characteristic features of this latter condition may not become evident until some months after birth. PMID- 1444557 TI - Changes in the plasma aminogram of parenterally fed infants treated with dexamethasone for bronchopulmonary dysplasia. AB - A substantial increase in the plasma concentration of most amino acids was observed in 59 preterm infants with chronic lung disease soon after the initiation of dexamethasone therapy. The size of increase appeared to be dose related. This phenomenon is likely to be the result of steroid induced protein catabolism. Interestingly, neither phenylalanine nor tyrosine concentrations were significantly increased. PMID- 1444558 TI - Coagulation screening tests in high risk neonates: a prospective cohort study. AB - Forty seven infants in a prospective cohort of 170 high risk neonates without signs of overt bleeding had abnormal coagulation screening tests within 36 hours of birth. Early thrombocytopenia was a better predictor of prolonged prothrombin times and hypofibrinogenemia than very low birth weight, fetal growth retardation, or poor five minute Apgar scores. PMID- 1444560 TI - Recovery of intralipid from lumbar puncture after migration of saphenous vein catheter. AB - A term female infant was admitted to the intensive care unit with the diagnosis of tetralogy of Fallot with critical pulmonary stenosis. On the seventh day of life a long saphenous line was inserted that remained without complications until seven days later when the infant appeared septic. A lumbar puncture demonstrated the presence of intra-lipid in the cerebrospinal fluid that we interpreted as due to migration of the saphenous catheter. The child had an uneventful recovery. PMID- 1444559 TI - Clinical application of urine antigen detection in early onset group B streptococcal disease. AB - The aim of this study was to test the sensitivity and specificity of antigen detection for group B streptococcus (GBS) from the urine of neonates with early onset GBS sepsis. GBS sepsis was defined as early (< 48 hours) signs of sepsis in a neonate colonised with GBS. Neonates of 26 weeks' gestation or more, considered at risk for sepsis, were prospectively investigated for one year. Investigations included culture of superficial swabs to assess colonisation, blood culture, and the Wellcogen Strep B latex particle agglutination test on urine. Of 188 neonates investigated, 17 (9%) had GBS sepsis. The urine antigen test had a sensitivity of 88% and specificity of 98%. The positive predictive value was 79% and the negative predictive value 99%. Blood culture was positive in only five neonates (29%). The annual incidence of GBS sepsis was 4.0 per 1000 and of blood culture positive GBS disease was 1.2 per 1000 live births. Three neonates died. The application of the urine antigen test of clinical neonatal practice is discussed. PMID- 1444561 TI - Meconium ileus in the absence of cystic fibrosis. AB - Although meconium ileus in the absence of cystic fibrosis is considered a rare event, it was found that eight of 37 (21.6%) newborn infants with meconium ileus had no laboratory or clinical evidence of cystic fibrosis. PMID- 1444562 TI - Validation of a portable indirect calorimetry system for measurement of energy expenditure in sick preterm infants. AB - A portable indirect calorimeter adapted from adult use was validated for use in preterm infants. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were subsequently measured in 16 preterm infants breathing spontaneously in room air (canopy mode) and in nine preterm infants receiving intermittent positive pressure ventilation (ventilator mode). Validation of the system was performed using a gas injection technique with nitrogen to simulate VO2 and carbon dioxide for VCO2. Mean errors in validation of the canopy mode were 1.4% and 0.2% for VO2 and VCO2 with limits of agreement of 0.6 (+2SD) ml/min and -1.3 (-2SD) ml/min, and 0.9 (+2SD) ml/min and -2.3 (-2SD) ml/min respectively. In validation of the ventilator mode mean errors were -1.8% and -5.05% for VO2 and VCO2 with limits of agreement of 1.02 (+2SD) ml/min and -0.74 (-2SD) ml/min, and 0.93 (+2SD) ml/min and -1.45 (-2SD) ml/min respectively. Values of VO2 and VCO2 in 16 preterm infants in the canopy mode were 6.2 ml/kg/min (0.5 1SD) and 6.7 ml/kg/min (0.6 1SD) and in nine preterm infants in the ventilator mode 4.98 ml/kg/min (1.09 1SD) and 4.74 ml/min/kg (1.08 1SD) respectively. Mean energy expenditure was 45.5 kcal (191 kJ)kg/day for infants measured in the canopy mode and 35.5 kcal (149 kJ)/kg/day for ventilated infants. This metabolic system can be adapted for use in the newborn but accuracy is reduced when it is used in those weighing less than 1000 g. PMID- 1444563 TI - Fatal perinatal nephropathy with onset in intrauterine life. AB - A girl, born at 29 weeks' gestation, died of renal failure aged 16 days. Postmortem histology showed diffuse mesangial sclerosis with failure of development of the cortex. This is an unusual cause of neonatal renal failure, and it demonstrates the effect of disease arising in utero and influencing the development of the kidney. PMID- 1444564 TI - When will my baby go home? AB - The length of stay of preterm babies discharged from a neonatal nursery was determined and the predictive value of perinatal factors on the duration of stay was assessed on 762 preterm Salford born babies admitted to Hope Hospital neonatal unit between April 1986 and November 1990. The data were analysed using multiple logistical regression and forward stepwise regression analysis. Babies were discharged at a median (quartile range) postconceptional age of 36.3 (35.3 37.6) weeks. Seventeen factors were found to be strongly predictive of discharge date. The most significant predictive factor was gestational age accounting for 40% of variability compared with respiratory difficulties (6%), low birth weight (4%), sepsis (2%), and metabolic problems (1%). Most babies are discharged at approximately the same postconceptional age despite variations in their clinical course. Gestational age at birth is the most powerful predictive factor of time of discharge. PMID- 1444565 TI - Intermittent ductal patency in healthy newborn infants: demonstration by colour Doppler flow mapping. AB - Colour Doppler flow mapping was used to determine the time of closure of the arterial duct in 51 healthy newborn infants. Initial time of closure corresponded with previous reports: 20% on the first day, 82% by the second day, 96% by the third day, and 100% by the fourth day. Twenty infants were delivered by caesarean section and followed up for seven days even if the duct had apparently closed; in six intermittent patency was demonstrated with flow in the third, fourth or fifth day, although earlier functional closure had been observed. All were found to be closed on the sixth and seventh days. It is necessary to be aware of the phenomenon of intermittent closure in any study determining or assessing the effect of any intervention on ductal patency. PMID- 1444566 TI - Neonatal meningococcal conjunctivitis associated with meningococcal meningitis. AB - Two infants are described in whom identical strains of meningococcus were isolated from both the eyes and the cerebrospinal fluid. This suggests that the eye may be a portal of entry in at least some cases of perinatally acquired neonatal meningococcal disease and has important implications for the management of purulent conjunctivitis in the newborn. PMID- 1444567 TI - Development of audit measures and guidelines for good practice in the management of neonatal respiratory distress syndrome. Report of a Joint Working Group of the British Association of Perinatal Medicine and the Research Unit of the Royal College of Physicians. PMID- 1444568 TI - Diagnosis and management of inborn errors of metabolism--an update. PMID- 1444569 TI - Initial experience of screening for retinopathy of prematurity. PMID- 1444571 TI - Felix Wurtz of Basel (1518-75) and clubfeet. PMID- 1444570 TI - The unreactive fetal heart rate. PMID- 1444572 TI - Renal candidiasis in the preterm infant. PMID- 1444573 TI - Stillbirths and non-lethal abnormalities--a mechanism of death? PMID- 1444574 TI - Clinical, light and electron microscopic features of recessive ichthyosis congenita type III. AB - The recessively inherited congenital ichthyoses have ultrastructural features which indicate abnormal epidermal lipid metabolism. The ultrastructural markers of the three recessive congenital ichthyosis groups are lipid droplets in horny layers (type I), cholesterol clefts (type II) and membrane structures (type III). We describe six patients from five families belonging to the last group. The variable clinical phenotype alone does not allow the delineation of this disease, but together with the ultrastructural characteristics the subtype is unequivocal. In addition to the membrane structures, half of the cases showed abnormal keratinosomes and vesicular complexes. Membrane-bound vacuoles and needle-like slits were exceptionally found. The onset of the ichthyosis was variable, in contrast to other patients described under the heading recessive congenital ichthyosis. PMID- 1444575 TI - Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha. AB - The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna. PMID- 1444576 TI - Increase in types IV and VI collagen in cherry haemangiomas. AB - The capillaries in cherry haemangiomas show perivascular hyalinized sheaths. In order to clarify the nature of this sheath material, the extracellular matrix of cherry haemangiomas from 20 normal volunteers (age range 30-64 years) was investigated using immunohistochemical and electronmicroscopical methods. Antibodies against collagen types III, IV and VI and laminin were used. Hyaluronic acid was visualized using the hyaluronic acid binding region of the cartilage proteoglycan as ligand. Electronmicroscopically, the sheaths contained multilaminated basement membrane-like material, collagen fibres 20-25 nm thick with a periodicity of 67 nm and broad-banded aggregates with a periodicity of 100 nm (zebra bodies or fibrous long-spacing fibres). Immunohistochemically, type IV collagen was stained throughout the whole sheath material. Staining for laminin was more confined to the endothelial side of the sheath. Intense staining for type III collagen and hyaluronic acid was found in the connective tissue of the subpapillary layer and between the cherry haemangioma capillaries. Much weaker staining for type III collagen and no staining for hyaluronic acid were found invariably in an area 4-10 microns thick directly around the capillaries. Both sheath material and intercapillary connective tissue of the haemangiomas showed pronounced staining for collagen type VI. Immunogold staining revealed that type VI collagen was localized to microfibrils 5-6 nm thick and to the broad-banded aggregates with 100 nm periodicity. These findings further underline the assumption that the broad-banded aggregates consist of type VI collagen. PMID- 1444578 TI - Effects of cepharanthine and minoxidil on proliferation, differentiation and keratinization of cultured cells from the murine hair apparatus. AB - The effects of cepharanthine and minoxidil on proliferation, differentiation and keratinization of cultured cells from the murine hair apparatus were examined electron microscopically. Both cepharanthine and minoxidil stimulated cell proliferation and delayed initiation of differentiation and keratinization of the cultured cells. On day 6, most control cells (87%) cultured in a 0.03 mM calcium medium without cepharanthine and minoxidil were differentiated into several subpopulations corresponding to those of in vivo cell layers of the hair apparatus, while most of the cells cultured with cepharanthine (71%) or minoxidil (70%) were still immature. On day 13, the number of degenerated cells increased (63%) in the control culture, whereas in the culture treated with cepharanthine or minoxidil, cell degeneration scarcely occurred (5% and 8%, respectively). Differentiated cells having tonofilaments were often observed in the cepharanthine- and minoxidil-treated cultures (76% and 72%, respectively). Elevation of extracellular calcium up to 1.0 mM induced keratinization (34%) in the control culture on day 6, while no keratinized cells were observed in the cepharanthine- or minoxidil-treated culture. On day 13 keratinization similarly occurred in the cultures with cepharanthine (30%) or minoxidil (48%). These results show that both cepharanthine and minoxidil may directly influence proliferation, differentiation and keratinization of cultured cells from the hair apparatus. PMID- 1444577 TI - Immunochemical detection of unrepaired cyclobutane-type pyrimidine dimers of DNAs extracted from human skin tumours. AB - Unrepaired cyclobutane-type pyrimidine dimers of DNA extracted from human skin tumours were examined by an immunoblotting method using polyclonal antibodies raised against UV-irradiated calf thymus DNA. A total of 40 DNA samples extracted from seven SCC lesions, two AK lesions, two lymphomas, one basal cell epithelioma, one eccrine poroma, one neurofibroma of Recklinghausen's disease, on verruca vulgaris, four femoral normal skins and white blood cells of 21 humans were studied by immunoblotting using this antibody. Two of the 40 DNAs examined, one from facial actinic keratosis (AK) and one from a squamous cell carcinoma (SCC) which developed form facial AK formed immunoprecipitates. It was found, using photoreactivation enzyme plus visible light, that both immunoprecipitates were cyclobutane-type pyrimidine dimers. In addition, immunofluorescent studies on AK tissue were positive in an immunoblotting assay and revealed that the unremoved photodamage in DNA remained in the nucleus of AK cells. These findings indicate that these tumour cells may be deficient in the enzyme function for repairing photoproduct damage. The unrepaired cyclobutane-type pyrimidine dimer in AK cells might reflect the genetic process in multistage carcinogenesis as well as in xeroderma pigmentosum. PMID- 1444579 TI - A murine in vitro model of allergic contact dermatitis to sesquiterpene alpha methylene-gamma-butyrolactones. AB - The use of a lymphocyte transformation test (LTT) to provide evidence of allergic contact dermatitis was investigated. The haptens studied were alantolactone and isoalantolactone, two moderate allergens from Inula helenium L., a decorative and medicinal plant. Only alantolactone showed a significant response in vivo and in vitro in mice sensitized epicutaneously, without using Freund's complete adjuvant. Isoalantolactone did not show any sensitizing capacity in the murine model studied. The comparison of in vitro lymphocyte proliferation and in vivo allergenic capacity showed a good correlation and clearly demonstrates that, of the two sesquiterpene lactones, alantolactone is the better sensitizer. PMID- 1444580 TI - Basal lamina-like material and hemidesmosome-like structures associated with dermal papilla cells in the normal human anagen hair follicle. PMID- 1444581 TI - Immunohistochemical localization of calmodulin in normal human epidermis. PMID- 1444582 TI - The analysis of IgG subclasses of anti-intercellular antibodies in pemphigus by an immunoblot technique. PMID- 1444583 TI - Increased immunoreactive interleukin-5 levels in blister fluids of bullous pemphigoid. PMID- 1444585 TI - Structural changes of proteins in fish red blood cells after copper and mercury treatment. PMID- 1444584 TI - Ultrastructural changes in Dunaliella minuta following acute and chronic exposure to copper and cadmium. AB - The ultrastructural changes taking place after short-term acute exposure to copper, cadmium and a combination of the two metals were examined. Additionally, the effects of long-term (8 months) exposure to ambient concentrations of these metals were investigated. Exposure to 0.34 microM cadmium affected the photosynthetic potential of this alga, by reducing the relative volume of the chloroplast by 23.27%. It also led to 74.6% increase in the relative volume of starch granules. Cells challenged with 0.34 microM cadmium and 7.57 microM copper had 33.49% larger volumes than controls, and their relative lipid volumes increased by 170%. In contrast, the relative volume of their pyrenoids decreased by 41.46%. Similar results were obtained after chronic exposure to 4.9 x 10(-4) microM copper with the relative volume of the pyrenoid being 28% smaller than the controls. PMID- 1444586 TI - Heavy metal and selenium concentrations in black skimmers (Rynchops niger): gender differences. AB - Most studies of heavy metals and selenium have not examined or have failed to find differences in concentrations in the tissues of birds as a function of size or sex. Heavy metal and selenium concentrations were analyzed in breast feathers of adult black skimmers Rynchops niger, a species with marked sexual size dimorphism in which males average 35% heavier than females. Females had significantly higher concentrations of lead and cadmium than males, but there were no gender differences in mercury, selenium, chromium, manganese, and copper despite the marked sexual dimorphism in body size. There were no significant correlations of bird weight or wing length and metal and selenium concentrations, and few correlations among metal and selenium concentrations in the feathers. PMID- 1444587 TI - Heavy metal and selenium levels in young cattle egrets from nesting colonies in the northeastern United States, Puerto Rico, and Egypt. AB - Colonially-nesting species of herons and egrets breed mainly in coastal areas, along rivers or near other large bodies of water. Such areas are also preferred for human development, exposing nesting birds to various pollutants. From 1989 1991, the concentrations of heavy metals and selenium were studied in the feathers of fledgling cattle egrets Bubulcus ibis, a terrestrially-feeding insectivore, from New York and Delaware in the northeastern United States, from Puerto Rico, and from Egypt. There were geographic differences in the concentrations of lead, mercury, cadmium, manganese, selenium, and chromium in the feathers of these egrets. Lead levels were 41 times higher in the feathers of cattle egrets from Cairo compared to the other sites. This difference was attributed to the continuing use of leaded gasoline and the dense automobile traffic in Cairo. However, other differences remain unexplained. Similarly, levels of chromium and manganese were also higher in Cairo than at any other sites. Cadmium levels were similar at all places except for higher levels in eastern Puerto Rico. Mercury concentrations were twelve times higher in the feathers of cattle egrets at Aswan compared to Cairo. In Puerto Rico, we also compared levels in adult cattle egrets with young and found higher concentrations of mercury and manganese, but lower concentrations of selenium in the adults. Using feathers from young cattle egrets is a potentially sensitive tool for biomonitoring for metals, especially lead, since they reflect the local area surrounding the breeding colony. PMID- 1444588 TI - The toxicity of selenium in experimental freshwater ponds. PMID- 1444589 TI - Subchronic toxicity and reproduction effects of tri-n-butyltin oxide in Japanese quail. AB - A subchronic toxicity/reproduction study was performed in Japanese quails that were fed a diet containing 0, 24, 60, and 150 mg tri-n-butyltin oxide (TBTO) per kg basal diet for 6 weeks. Eggs produced during the 6 weeks of treatment were incubated and hatched, and chicks hatched from eggs collected in weeks 5 and 6 of exposure were reared for 2 weeks. In parent quail, neither diminished food consumption nor any overt toxic or histopathologic signs were observed following exposure to TBTO. A statistically significant decrease in hatch-ability and increase in percent of chicks found dead in the shell were observed following TBTO exposure at concentrations of 60 and 150 mg/kg food. However, no significant, adverse effects were recorded on total egg production, eggshell thickness and cracked eggs. Blood chemistry parameters of birds measured at the last day of TBTO treatment revealed a statistically significant decrease in serum aspartate aminotransferase (ASAT) enzyme activity among both sexes in all treatment groups. In addition, a statistically significant dose-related decrease in serum calcium level was observed in females only, while serum follicle stimulating hormone (FSH) levels were statistically significantly reduced in male birds in all treatment groups (approximately 50% of the controls). Moreover, a significant decrease in hepatic microsomal 7-ethoxyresorufin (EROD) activity was recorded in females fed 24 and 60 mg TBTO/kg diet and males fed 60 and 150 mg TBTO/kg diet, whereas pentoxyresorufin-o-deetylase (PROD) activity was only significantly decreased in males fed 150 mg TBTO/kg diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444590 TI - Hydrolysis of ochratoxin A by the microbial activity of digesta in the gastrointestinal tract of rats. AB - This study established the influence of dietary neomycin sulphate on the rate of hydrolysis of ochratoxin A (OA) by digesta from the intestine, and its effect on the excretion of OA and its hydrolyzed metabolite, alpha ochratoxin (O alpha), in the urine and feces of the rat. The first in vitro study demonstrated that digesta from the cecum and the large intestine were able to hydrolyze OA whereas digesta from the small intestine and stomach had very low hydrolytic activity against this substrate. Homogenates of the liver had no hydrolytic activity. The second in vivo study demonstrated that digesta from the large intestine and cecum of the neomycin treated rats was much less effective (P < 0.001) in promoting the hydrolysis of OA than digesta from the control rats. Neomycin when added directly to the in vitro system, however, did not affect the rate at which OA was hydrolyzed. In a third study, OA was administered in vivo to control and neomycin treated rats. Rats fed the neomycin containing diet compared to those fed the control diet had a higher concentration (P < 0.005) of blood OA, and a greater cumulative excretion of OA plus O alpha over the entire 5 day collection period in the feces (P < 0.0001) and a corresponding decrease in the cumulative excretion of OA plus O alpha in the urine (P < 0.0001). Individually, there was a marked increase in cumulative fecal excretion of OA (P < 0.05) and a corresponding decrease in excretion of O alpha (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444591 TI - Disposition, behavior, and toxicity of methylcyclopentadienyl manganese tricarbonyl in the mouse. AB - The disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT), a potential substitute for lead in gasoline, was studied to investigate the different adverse effects in ddY mice after chronic oral administration at 0.5 g/kg in food for 12 months. There was no significant difference in intake between the control mice and the mice exposed to MMT (MMT group), but those given MMT suppressed weight significantly. The manganese content in the organs of the MMT group was 4.4-1.5 times significantly higher than that of the control group. In the MMT group, the manganese content was highest in the kidney, followed by the liver, thyroid gland, sublingual gland, and prostate gland. The blood manganese level in the MMT group was about 8 times higher than that in the control group. The urinary excretion of manganese in the MMT group was 5.4% of the daily oral intake. The organometallic form of the manganese involved is apparently absorbed more readily than inorganic forms. The stronger toxicity of MMT to the tissue than that of inorganic manganese is attributed to the significantly higher blood and tissue levels of manganese in the MMT group. PMID- 1444592 TI - Temporal scales in ecological risk assessment. AB - The process of human health risk assessment (HRA) was formalized in 1983 by the National Research Council to include hazard identification, dose-response analyses, exposure assessment and risk characterization. Risk assessment for ecologic endpoints is emerging as a new discipline. Although environmental impact statements have been conducted for many years, ecologists, managers and policy makers are beginning to formalize the process in terms of risk, and are adapting the HRA paradigm to ecological risk assessment (ERA). In this paper it is suggested that the temporal scales of the two processes differ, and that these differences should be incorporated in ecological risk assessment. Even when HRA techniques are applied to a single non-human species there are temporal variations including: (1) different and often variable life spans, (2) unpredictable lengths of lifestages and different metamorphic stages, and (3) indeterminate growth in some species. When these differences are considered for multispecies assemblages, the impact on the food web will result in exposures of differing magnitudes affecting different species. The challenges for ERA include developing general principles for estimating or predicting exposure to critical life stages of the dominant species in an ecosystem, and establishing the appropriate temporal scales for predicting impacts or evaluating outcomes. PMID- 1444593 TI - Aircraft noise annoyance and average versus maximum noise levels. AB - A questionnaire study was performed in seven areas located around the airports of Landvetter and Save, Gothenburg, in an attempt to elucidate the extent of annoyance in populations exposed to aircraft noise. Noise exposure was estimated as the energy equivalent level (Aircraft Noise Level--FBN) or as the number of aircraft with levels that exceeded 70 dBA, combined with the maximum noise level. The results were compared with data obtained from the earlier Scandinavian Aircraft Noise Investigation. The results supported the conclusion that the annoyance reaction is better related to the number of aircraft and the maximum noise level than to energy equivalent levels for noise exposure. PMID- 1444594 TI - Bone lead measurements in patients with chronic renal disease studied over time. AB - Results of longitudinal studies that involved the measurement of lead by different methodologies are presented for two groups of patients with chronic renal disease. Methodologies for all patients included x-ray fluorescence measurements of finger-bone lead. These measurements were conducted 5 y apart for one group of patients (n = 15). Initial measurements for the other group (n = 15) were supplemented by bone lead levels obtained either from skull at craniotomy or from skull, and sometimes rib, at autopsy. Most subjects also underwent ethylenediaminetetraacetic acid (specifically CaNa2 EDTA) lead-mobilization testing. A correlation between rate of decrease in finger-bone lead and immunoreactive parathormone levels was suggested. Renal patients were compared with age-matched controls, and their bone half-lives did not differ. The data are discussed and related to other results obtained from clinical and nonclinical populations in which trabecular and cortical bones were studied, and our results were consistent with evidence that more rapid turnover of lead occurs in trabecular bone than in cortical bone. No support was found for the hypothesis that patients who undergo renal dialysis accumulate lead in bone. PMID- 1444595 TI - Effect of low-level body burdens of lead on the mental development of children: limitations of meta-analysis in a review of longitudinal data. AB - The effect of low-level body burdens of lead on the intelligence of children, as measured by intelligence quotient (IQ), was assessed. We reviewed 35 reports from five longitudinal studies conducted in the United States and Australia. In each of these studies, infants were followed for 58 mo or less. The study populations consisted of low- and middle-socioeconomic-class infants who had low-level exposure to environmental lead. Blood-lead levels were measured in a standard fashion at various times, beginning in the prenatal period, and intelligence was first measured at 6 mo of age and was followed by subsequent assessments. Studies were assessed for quality by a review panel blinded to the identity of the investigators and their affiliations. Efforts were made to pool the data with meta-analytic techniques, but efforts were unsuccessful because the methods used to analyze and report data were inconsistent. Inconsistencies were as follows: (a) there were few instances in which IQ and blood-lead levels were measured at comparable times in different studies; (b) incompatibilities existed among the studies, including differences in independent variables, data transformations, and statistical parameters reported; (c) results conflicted when measurement intervals were comparable (i.e., heterogeneity); (d) patterns of regression and correlation coefficients were inconsistent; and (e) data were insufficient to interconvert the parameters reported. Consequently, definitive conclusions regarding the effect of low-level body burdens of lead on IQ could not be determined from the longitudinal data. Examination of the weight of the evidence from this and other studies, however, suggests an adverse relationship of lead on the intelligence of children. PMID- 1444596 TI - Impact of environmental cadmium pollution on cadmium exposure and body burden. AB - The body burden of cadmium, as estimated from 24-h urine cadmium levels, was determined in 1,523 subjects who were not occupationally exposed and who lived in five areas of Belgium. Urinary cadmium levels differed significantly with place of residence. These differences persisted after standardization for the other significant determinants (i.e., age, body mass index, smoking habits, social class, alcohol consumption, and menopause). The highest 24-h urine cadmium levels were found in subjects who lived in areas that contained cadmium-polluted soils. The body burden overload has been attributed mainly to the consumption of locally grown vegetables and the use of contaminated well water for cooking and drinking. Blood cadmium levels were also dependent on place of residence. However, the geographical differences in blood cadmium did not parallel those of urine cadmium. Blood cadmium is more influenced by recent exposure; therefore, this latter observation might reflect the recent implementation of preventive measures in some areas. PMID- 1444597 TI - Decrease in blood cadmium levels over time in Belgium. AB - During the time period from 1984 to 1988, blood cadmium concentration decreased by 56% in 31 males who were not occupationally exposed to cadmium and who lived in a Belgian urban area where there existed nonferrous industries. A 40% decrease in blood cadmium concentration was also observed in an independent cross sectional survey conducted in 1985 and 1988 among 412 subjects who lived in a rural area. This latter decrease persisted when the main determinants of blood cadmium concentration--gender, age, and tobacco--were allowed for. The results presented are consistent with a decrease in environmental cadmium exposure in Belgium. PMID- 1444598 TI - Exposure to environmental tobacco smoke in the household and urinary cotinine excretion, heavy metals retention, and lung function. AB - The relationship between urinary levels of cotinine (U-cotinine) and arsenic (U As), blood levels of cadmium (B-Cd), blood levels of lead (B-Pb), lung function, and questionnaire data on smoking habits were studied in 107 parents and their 46 children (7-10 y of age). There was a statistically significant relationship between the reported amount of tobacco smoked and U-cotinine levels. Nonsmokers who were married to persons who smoked had three times higher U-cotinine levels than nonsmokers whose spouses did not smoke. There was a significant association between the number of parents who smoked in the family and the U-cotinine levels of children. If only one parent smoked, maternal smoking was of greater importance than paternal smoking. There was also an association between U cotinine and B-Cd. A study of lung function in the children revealed that vital capacity and functional residual capacity (corrected for sex, age, and height) increased as the number of parents who smoked increased. Therefore, the present study showed that (1) U-cotinine was a useful index of active smoking and environmental tobacco smoke exposure in adults and children, (2) U-cotinine was associated with the blood concentration of cadmium, and (3) environmental tobacco smoke exposure was associated with changes in lung function of children. PMID- 1444599 TI - Respiratory health effects of alkali dust in residents near desiccated Old Wives Lake. AB - Several years of drought have contributed to the desiccation of Old Wives Lake, a shallow, alkaline lake in southern Saskatchewan. The prevailing northwest wind, which blows across the 177-km2 dry lake bed, has generated airborne sodium sulfate, silt, and clay. Residents have reported nasal, eye, and respiratory irritation. A cross-sectional design that included 300 controls and 300 exposed subjects elucidated the potential adverse respiratory health effects of exposure to blowing alkali salt and dust. An increased prevalence of current cough, current wheeze, chronic cough, chronic wheeze, chronic eye irritation, and chronic nasal irritation was identified in the exposed population. Smoking adjusted odds ratios were consistent with the prevalence ratios. Lung function did not differ between the exposed and the control populations. Rainfall during the study period reduced airborne dust levels and may have precluded demonstration of previously reported adverse effects. PMID- 1444600 TI - Lead acetate does not impair secretion of Sertoli cell function marker proteins in the adult Sprague Dawley rat. AB - This study was conducted to determine the effects of lead on Sertoli cell function. Androgen binding protein and inhibin in testicular fluids and classical parameters of the hypothalamic-pituitary-gonadal axis were measured in adult male rats. For 10 wk, the rats were given water that contained 0.05%, 0.1%, 0.5%, and 1% lead acetate. Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels in all animals that ingested lead were normal at the middle and end of the experiment, as was the pituitary content of follicle-stimulating hormone and luteinizing hormone. Histologic examination revealed no disruption of spermatogenesis. Distribution of androgen binding protein in serum, seminiferous tubular fluid, and interstitial fluid was normal, as was the concentration of inhibin in interstitial fluid and seminiferous tubular fluid. However, a significant increase in epididymal androgen binding protein level and a decrease in seminal vesicle weight were observed in rats that ingested water containing 1% lead acetate. These results suggest that the effect of lead on spermatogenesis is not marked in adult Sprague Dawley rats, nor does Sertoli cell function appear to be affected adversely. Lead has been reported to alter in vitro metabolic function of Sertoli cells obtained from 16- to 21-d-old Sprague Dawley rats, and the Sertoli cells of juvenile animals may be more susceptible to lead than those of adult animals. The significant decrease in seminal vesicle weight and the abnormal epididymal androgen binding protein content indicate that lead could affect the male reproductive function in Sprague Dawley rats via its action on male accessory organs. PMID- 1444601 TI - Nitrogen dioxide exposure and urinary excretion of hydroxyproline and desmosine. AB - The relationship between average and peak personal exposure to nitrogen dioxide and urinary excretion of hydroxyproline and desmosine was investigated in a population of preschool children and their mothers. Weekly average personal nitrogen dioxide exposures for subjects who resided in homes with one or more potential nitrogen dioxide source (e.g., a kerosene space heater, gas stove, or tobacco smoke) ranged between 16.3 and 50.6 ppb (30.6 and 95.1 micrograms/m3) for children and between 16.9 and 44.1 ppb (12.8 and 82.9 micrograms/m3) for mothers. In these individuals, the hydroxyproline-to-creatinine and desmosine-to creatinine ratios were unrelated to personal nitrogen dioxide exposure--even though continuous monitoring documented home nitrogen dioxide concentration peaks of 100-475 ppb lasting up to 100 h in duration. Significantly higher hydroxyproline-to-creatinine and desmosine-to-creatinine ratios were observed in children, compared with mothers (p < .001 and .003, respectively). PMID- 1444603 TI - Environmental odor pollution. PMID- 1444602 TI - On the bioavailability of methyl isocyanate in the Bhopal gas leak. PMID- 1444604 TI - [The American Confederation of Urology and the 5th centennial]. PMID- 1444605 TI - [Telesurgery]. PMID- 1444606 TI - [Stress urinary incontinence. Our results with the Burch's technique]. AB - The aim of the surgical procedures utilized in the treatment of stress urinary incontinence (SUI) is to correct the posterior ureterovesical angle defect, thereby improving transmission of intraabdominal pressures to the urethra. We report our experience on 61 patients that had been diagnosed with SUI at our service from June 1984 to December 1990. Treatment was by the same operative procedure (Burch Technique) in all patients. The methods of exploration and the prognostic factors that might influence the outcome of the procedure are described. The short-term (3 months) success rate was 95%, the medium-term (1 year) 85.7% and the long-term (5 years) 77.1%. We underscore the convenience of prophylactic heparin therapy to prevent possible thromboembolic complications. PMID- 1444607 TI - [Spontaneous perirenal hematoma]. AB - We report 10 cases of spontaneous perirenal hematoma that had been treated from 1974 to 1992. Retroperitoneal hemorrhage was secondary to renal disease in 7 cases, perirenal in 2 and extrarenal in 1. The etiology of the condition is analyzed in detail and the diagnostic usefulness of the different radiologic examinations are discussed. Making a preoperative diagnosis permits a more adequate surgical strategy. PMID- 1444608 TI - [Bladder tumors: false recurrences]. AB - The use of the new cytostatics for prophylactic therapy of superficial bladder tumor recurrence has been associated with fibrino-necrotic ulcers and eosinophilic cystitis. We underscore the problems in making the differential diagnosis which sometimes present with true tumor necrosis. We describe the characteristic features of both pathological conditions which permit these to be recognized before endoscopic maneuvers are performed. Their presenting features and course are analyzed. PMID- 1444609 TI - [Mitoxantrone (MTX) versus mitomycin C (MMC) in the ablative treatment of Ta, T1 superficial bladder tumors. Phase III, randomized prospective study]. AB - A prospective randomized study was conducted to determine the ablation capacity of mitoxantrone in Ta-T1 superficial bladder tumors versus mitomycin C, a drug whose intravesical ablation properties are well-known. Fifty-seven patients comprised the study. The tumor was not completely resected when the patient underwent TUR. This residual tumor was used as control. The patients were treated with either 20 mg Mitoxantrone or 40 mg mitomycin C weekly for 8 weeks and two other instillations every 15 days in 50 ml saline solution. Response to therapy was evaluated between the 4th and 8th week and classified as complete response (CR), defined as no gross and microscopic evidence of residual tumor, or no response (NR) or therapeutic failure. CR was observed in 77.7% of the patients treated with mitomycin C and in 50% in those that had been treated with Mitoxantrone. Treatment was discontinued because of side effects in 15% of the patients treated with mitomycin C and in 63.4% of those who received Mitoxantrone. We can conclude from the results of the present study that Mitoxantrone is a useful agent for ablation therapy of superficial bladder tumors, although the high incidence of severe side effects warrants its limited use and at high dilutions. PMID- 1444610 TI - [Incidence of tumor pathology in a consecutive series of 497 kidney transplants in 431 patients]. AB - From 1975 to 1989, 497 kidneys were transplanted in 431 patients. In this series, 12 tumors were observed in 11 patients (2.7%). There was a prevalence of skin tumors over the other tumor types (33%). The mean time of tumor presentation was 49 months post-transplantation. We investigated the possible influence of immunosuppression on tumor presentation. In our series, immunosuppression therapy was modified in only one case (Kaposi's syndrome), and the initial dose was maintained in the remaining tumors. Of the 11 patients, 5 have died and the remaining 6 patients are alive with a mean follow-up of 34 months. PMID- 1444611 TI - [Clinico-therapeutic classification of urinary lithiasis]. AB - Urinary lithiasis is a millenary disease for which different classifications have been developed: clinical, etiopathogenic, crystallographic, etc. The introduction of endoscopic surgery and extracorporeal lithotripsy in the last decade has created the need for a clinicotherapeutic classification as manifested by Rocco, Griffith, Tisselius, and other authors. We have developed the CEP/LTS-X classification, which evaluates the stone characteristics (C) [location and form (L), size (T), consistency (S) and number (X)], the excretory tract (E) and the renal parenchyma (P), and permits classifying the urinary calculus as LTS renal calculus types I, II, III, IV; LTS ureteral calculus types I, II, III; and LTS vesical and ureteral calculi types I and II, with related general characteristics that permit indicating treatment for each type: in situ ESWL or complementary endourological techniques, endoscopic or open surgery, alone or in combination. PMID- 1444612 TI - [Ureteral tamponade in the treatment of urinary fistula: our experience]. AB - Surgical correction is the treatment of choice for urinary fistulas. However, there are circumstances that advise against the use of this approach, basically when patient general condition is poor or life expectancy short; i. e., in the presence of an underlying malignant pelvic disease. In these cases, urinary diversion by percutaneous nephrostomy will suffice, although sepsis or derangement of electrolyte balance may sometimes develop due to the fistulous defect. Occlusion of the pyelo-ureteric junction and percutaneous drainage is a solution that causes no major complications. Two patients who could not be submitted to conventional surgery were treated by the foregoing procedure. Both patients have been followed for more than two years. The first case was a male who had undergone abdominoperineal resection due to carcinoma of the sigmoid colon. He developed stress ulcers, pulmonary thromboembolism, sepsis, paralytic ileus and bilateral ureteral fistula. The second case was an insulin-dependent female diabetic who had previously received radiotherapy to the pelvis. She developed a large vesicocutaneous fistula and public osteomyelitis after drainage of an inguinal abscess. Patient tolerance was good and no major complications were observed. In our view this palliative procedure should be considered in the management of patients with urinary fistula whose life expectancy is short. Its application can be extended to patients with inoperable carcinoma of the bladder or prostate and important symptoms. PMID- 1444613 TI - [Ureteral revascularization in kidney transplantation. Report of a case]. AB - We present uretero-pyeloplasty as a new surgical approach to stricture of the pyelo-ureteric junction in the transplant recipient. The foregoing is more frequently found in kidneys that are placed in the inverted anatomic position. The surgical procedure is performed without difficulty and at the same time permits us to evidence the presence of a new ureteral revascularization from the recipient after the interruption of vascular supply of the donor kidney. PMID- 1444614 TI - [Nephrectomy following treatment with ESWL of staghorn lithiasis complicated with urinoma]. AB - We report on a female patient that had undergone extracorporeal shock wave lithotripsy for a staghorn stone. We describe the endourological maneuvers that were performed, but had failed to avoid nephrectomy due to renal fistula with urinoma. PMID- 1444615 TI - [Normal echographic anatomy of the penis and the perineum]. AB - Sonourethrography has recently become available for evaluating the urethra. To perform this procedure correctly, precise knowledge of the ultrasound anatomy of the penis and perineum is required. Sixty-one males were studied using the 7.5 Mhz ultrasound transducer. During sonographic evaluation the site where the suspensory ligament of the penis is attached must be identified routinely. The nothc of the compressor nudae muscle in the posterior bulbous urethra can be visualized occasionally. The origin of the membranous urethra and urogenital diaphragm can be identified upon visualizing the entire urethral bulb and the cavernous bulb muscle. PMID- 1444616 TI - [Bilateral renal lymphoma]. AB - Lymphomas can present as a solid tumor mass in one or both kidneys or compromise renal function directly or indirectly. Lymphoma should be discarded before performing surgical excision of a rapidly growing renal mass, particularly if involvement is bilateral. Reducing the renal mass may lead to difficulty in instituting specific chemotherapy for this tumor type. PMID- 1444617 TI - [Non-venereal sclerosing lymphangitis of the penis]. AB - Non-venereal sclerosing lymphangitis of the penis is a rare condition that affects the distal lymphatics of this organ. It has been reported to be frequently associated with trauma to this area and, although it has a minimum inflammatory component, its etiology is unknown. A serpinginous nodular lesion in the sulcus coronarius penis may be observed by the patient. Because it is generally self-limiting, treatment is initially conservative and surgical excision is performed only if symptomatic lesions persist. The present study reports an additional case. The literature is reviewed and the possible etiopathogenic mechanisms and therapeutic alternatives are discussed. PMID- 1444618 TI - [Bladder schistosomiasis: presentation of a new case]. AB - We report a case of urinary schistosomiasis involving only the bladder and mimicking a transitional cell pseudotumor. We describe the clinical and pathological features and discuss the diagnosis, medical and surgical treatment of this disease entity whose incidence is slowly increasing in black immigrants of the Maresme area of Barcelona. PMID- 1444619 TI - [Liposarcoma of spermatic cord. A rare urologic tumor]. AB - Malignant paratesticular tumors are uncommon. Of these, liposarcoma of the spermatic cord constitutes a rare tumor type with a good prognosis. It has a high rate of survival over 5 years. Inguinal orchiectomy generally suffices, although patients should be followed closely since local recurrence is not uncommon. The present study briefly reviews the literature on spermatic cord liposarcoma and reports an additional case that was treated exclusively by radical orchiectomy. Four years postoperatively the patient continues to be tumor-free. PMID- 1444620 TI - [Acute adrenal hemorrhage and contralateral renal adenocarcinoma]. AB - We report a case of spontaneous retroperitoneal hematoma from rupture of the right adrenal in a patient with asymptomatic left renal adenocarcinoma that had been incidentally detected during evaluation to determine the cause of the retroperitoneal hematoma. PMID- 1444621 TI - How serious is knee osteoarthritis? PMID- 1444622 TI - Radiological progression of osteoarthritis: an 11 year follow up study of the knee. AB - A follow up study was carried out in 1990 on 169 well documented patients initially presenting with osteoarthritis of the hands or knees between 1975 and 1977. Radiographic change in the knee was used as the outcome measure. Sixty three subjects had paired knee radiographs a mean of 11 years apart and were 69 (range 52-87) years old at follow up. Thirty subjects were known to have died, 28 were untraceable, and 48 were traced but did not have paired films available. The films were read independently and blind to time sequence by two observers using five different radiological scoring methods. Most of the knees did not increase in Kellgren and Lawrence grade, with only 33% deteriorating over the time period. The results were similar when a subject was categorised by their worst knee. When a more sensitive global score on paired films was used 50% of knees showed a slight deterioration and 10% improved. Visual analogue pain scores remained unchanged. Those with knee pain at baseline had a greater chance of progressing, as did those with existing osteoarthritis in the contralateral knee. These results suggest that most patients with osteoarthritis attending rheumatology clinics do not deteriorate radiographically or symptomatically over an 11 year period. More work is needed in the selection and early detection of subjects with a poor prognosis and in focusing early intervention on this high risk group. PMID- 1444623 TI - Radiographic patterns and associations of osteoarthritis of the hip. AB - A number of patterns of osteoarthritis of the hip are described, though studies are conflicting with respect to the frequency of such patterns and their associations. Two hundred and eleven patients (133 women, 78 men; mean age 66 years, range 29-86) referred to hospital with osteoarthritis of the hip were studied. Involvement was unilateral in 108 (51%) and bilateral in 89 (42%); 14 (7%) had undergone arthroplasty and were presenting with osteoarthritis hips). Sixty one per cent of hips had severe, 28% moderate, and 11% mild changes (Kellgren grade). Superior pole migration occurred in 82% (46% superolateral, 25% intermediate, 11% superomedial), medial/axial migration occurred in only 8%, and in 10% the pattern was indeterminate. In bilateral osteoarthritis of the hip the pattern was generally symmetrical. Superomedial and medial/axial patterns were proportionately more common in women, whereas superlateral osteoarthritis predominated in men. No association was found between multiple clinical nodes, radiographic polyarticular interphalangeal or first carpometacarpal osteoarthritis and any migration pattern. Any interphalangeal osteoarthritis was negatively associated with medial migration. Only 40% of hips could be categorised as hypertrophic or atrophic; chondrocalcinosis at any site was associated with atrophic osteoarthritis; no associations were seen with Forestier's disease. This large survey confirms the association between chondrocalcinosis and atrophic osteoarthritis of the hip. Importantly it suggests that gender, rather than associated osteoarthritis at other sites, is a major determinant of the pattern of osteoarthritis of the hip. PMID- 1444624 TI - Exercise induced release of von Willebrand factor: evidence for hypoxic reperfusion microvascular injury in rheumatoid arthritis. AB - Experimental evidence suggests that rheumatoid synovitis may be perpetuated by the generation of reactive oxygen species during hypoxic reperfusion injury. The latter occurs because increased intra-articular pressure during exercise exceeds synovial capillary perfusion pressure, impairing blood flow. The object of this study was to establish a marker for and the mechanism of synovial hypoxic reperfusion injury. Von Willebrand factor (vWF) is only released from endothelial cells and platelets and is an in vivo and in vitro marker of endothelial injury. In vivo exercise induced changes in plasma vWF were therefore investigated in patients with rheumatoid arthritis (RA) compared with controls and in vitro vWF release by human umbilical vein endothelial cells subjected to hypoxia reperfusion. Pre-exercise plasma vWF levels were 1001 and 817 IU/l, increasing after exercise to 1658 and 845 IU/l in patients with RA and controls respectively. Von Willebrand factor release from human umbilical vein endothelial cells followed a biphasic pattern, occurring during both hypoxia and reperfusion. Hypoxia reperfusion induced vWF release by human umbilical vein endothelial cells in vitro suggests that exercise induced vWF release in patients with RA is best explained by synovial hypoxic reperfusion injury. This study supports evidence that generation of reactive oxygen species plays a principal part in synovial hypoxic reperfusion injury and suggests vWF as a useful marker of this phenomenon. PMID- 1444625 TI - Relative contribution of contact and complement activation to inflammatory reactions in arthritic joints. AB - Although both the complement and contact system are thought to contribute to the inflammatory reaction in arthritic joints, only activation of complement has so far been well established, whereas contact activation and its contribution to arthritis has not been systematically explored. Complement and contact activation were assessed in 71 patients with inflammatory arthropathies and 11 with osteoarthritis using sensitive assays for C3a, and C1-inhibitor (C1INH) kallikrein and C1INH-factor XIIa complexes respectively. Increased plasma concentrations of kallikrein-and factor XIIa-C1INH complexes were found in two and seven of the 71 patients with inflammatory arthropathies, respectively, and in none of the patients with osteoarthritis. Increased synovial fluid concentrations of kallikrein and factor XIIa complexes occurred in 13 and 15 patients with inflammatory joint diseases respectively, and in two patients with osteoarthritis. Contact system parameters did not correlate with clinical symptoms, local activity, or neutrophil activation. In contrast, synovial fluid concentrations of C3a and C1INH-C1 complexes were increased in all patients and in 20 patients with inflammatory arthropathies respectively, and were higher in patients with a higher local activity score. Synovial fluid C3a correlated with parameters of neutrophil activation such as lactoferrin. Increased plasma concentrations of C3a and C1INH-C1 complexes occurred in 13 and 11 patients with inflammatory joint diseases, and in one and two patients with osteoarthritis respectively. Plasma concentrations of C3a correlated with the number of painful joints. Thus contact activation occurs only sporadically in patients with arthritis and contributes little if anything to the local inflammatory reaction and neutrophil activation. These latter events are significantly related to the extent of complement activation. PMID- 1444626 TI - Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases. AB - Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss. PMID- 1444628 TI - Central nervous system systemic lupus erythematosus mimicking progressive multifocal leucoencephalopathy. AB - The case is reported of a patient with central nervous system systemic lupus erythematosus (SLE) with features of progressive multifocal leucoencephalopathy (PML) seen clinically and by magnetic resonance imaging. A brain biopsy sample showed microinfarcts. The use of magnetic resonance imaging and IgG synthesis rates in evaluating central nervous system lupus, the co-occurrence of SLE and PML, and the differentiation of these entities by magnetic resonance imaging and by histology are considered. PMID- 1444627 TI - Measurement of HLA class I expression in ankylosing spondylitis. AB - The importance of HLA-B27 in the pathogenesis of ankylosing spondylitis is uncertain: current evidence favours a role for the B27 molecule itself. The possibility that quantitative differences in HLA-B27 expression may exist between patients with ankylosing spondylitis, family members, and control subjects positive for B27 was examined using appropriate monoclonal antibodies, flow cytometry, and a 'model lymphocyte' coated with a known number of mouse immunoglobulin binding sites. No differences were found between the groups. HLA A2, examined for comparison, was expressed in greater amounts than HLA-B27, but each contributed only 10-20% of the total class I antigens. Homozygotes expressed twice the amount of antigen expressed by heterozygotes. Synovial lymphocytes expressed more class I antigens than peripheral lymphocytes. PMID- 1444629 TI - Mixed connective tissue disease presenting as a left sided pleural effusion. AB - Mixed connective tissue disease (MCTD) usually occurs in women aged 13-50 years. Pleural effusion is rarely the presenting feature of this disease. The case is reported here of a male patient with MCTD who presented at the age of 79 years with a left sided pleural effusion. PMID- 1444630 TI - Scleromyxoedema with features of systemic sclerosis. AB - The case is described of a patient with scleromyxoedema with features typical of systemic sclerosis. The features were so characteristic that the disease was misdiagnosed as systemic sclerosis. A brief review of the association of the two diseases is given. PMID- 1444631 TI - Retrocalcaneal bursitis in juvenile chronic arthritis. AB - Retrocalcaneal bursitis has been described in various adult rheumatic diseases and septic bursitis unrelated to previous bursal disease has been reported in children. The case is reported here of a girl with juvenile chronic arthritis who developed non-septic retrocalcaneal bursitis; the diagnosis was suggested by a combination of clinical and radiographic studies and was confirmed by ultrasonography. PMID- 1444632 TI - The 'GALS' locomotor screen. AB - The locomotor system is complex and difficult to examine. A selective clinical process to detect important locomotor abnormalities and functional disability could prove valuable. A screen based on a tested 'minimal' history and examination system is described, together with a simple method of recording. The screen is fast and easy to perform. As well as providing a useful introduction to examination of the locomotor system, the screen includes objective observation of functional movements relevant to activities of daily living. Its inclusion in the undergraduate clerking repertoire could improve junior doctors' awareness and recognition of rheumatic disease and general disability. It could also provide a valuable screening test for use in general practice. PMID- 1444633 TI - Mycoplasmas and arthritis. PMID- 1444634 TI - The venous footpump: influence on tissue perfusion and prevention of venous thrombosis. PMID- 1444635 TI - Methotrexate, pneumonitis, and infection. PMID- 1444636 TI - Methotrexate, pneumonitis, and infection. PMID- 1444637 TI - The antiphospholipid syndrome: a syndrome in evolution. PMID- 1444638 TI - Anticardiolipin antibodies and renovascular hypertension. PMID- 1444639 TI - von Willebrand factor antigen in giant cell arteritis. PMID- 1444640 TI - Renal cell carcinoma with acute monarthritis. PMID- 1444641 TI - Systemic mastocytosis and Sjogren's syndrome. PMID- 1444642 TI - Unusual rhombencephalitis in relapsing polychondritis. PMID- 1444643 TI - Continuing evolution in the approach to severe liver trauma. PMID- 1444644 TI - Continuing evolution in the approach to severe liver trauma. AB - Surgical and radiologic techniques from computed tomography (CT) scanning and embolization to temporary gauze packing and mesh hepatorrhaphy have been developed to make the management of severe liver injuries more effective. Surgical approaches for severe liver trauma have been oriented to two major consequences of these injuries: hemorrhage and infection. Early attempts at hemorrhagic control found benefit only in temporary intrahepatic gauze packing. The subsequent recognition of complications after liver injury blamed the practice of packing, which then remained unused for more than 30 years. Yet more aggressive attempts at controlling hemorrhage without temporary packing failed to improve results. Temporary perihepatic gauze packing therefore has been reintroduced, but this is probably an imperfect solution. Mesh hepatorrhaphy may control bleeding without many of the adverse effects of packing. Fourteen patients are reported with severe liver injuries who have undergone mesh hepatorrhaphy, bringing the current reported experience with mesh hepatorrhaphy to 24, with a combined mortality rate of 37.5%. Thus far, it appears that only juxtacaval injuries fail to have their hemorrhage controlled with mesh hepatorrhaphy, but many believe that these injuries may be controlled by perihepatic packing. Prophylactic drainage of severe liver injuries is a concept for which there is little evidence of benefit. Furthermore, recent radiologic developments appear capable of draining those collections that do occasionally develop in the postoperative period. The ultimate challenge of liver transplantation for trauma has been attempted, but the experience is thus far very limited. PMID- 1444645 TI - Tumor necrosis factor alpha inhibits hepatocyte mitochondrial respiration. AB - Although direct cytotoxicity is a well-established phenomenon of tumor necrosis factor alpha (TNF alpha)-induced tissue damage, the intracellular events leading to cell death are still poorly understood. To study the cytotoxic effects of TNF alpha on normal parenchymal cells, rat hepatocytes were purified and incubated with various concentrations of TNF alpha. Mitochondrial respiration, total protein synthesis, and enzyme release were measured to assess metabolic performance and cell integrity. Treatment with TNF alpha suppressed mitochondrial respiration in a concentration-dependent fashion, resulting in a reduction of the activity of complex I of the respiratory chain to 67.0 +/- 3.5% of that of untreated hepatocytes by 2000 U/mL TNF alpha. Under these conditions protein synthesis and the release of intracellular enzymes were significantly increased. Both hepatocellular enzyme release and inhibition of mitochondrial respiration appear to be associated with the generation of reactive oxygen intermediates by the hepatocyte itself, because oxygen radical scavengers prevented these adverse effects of TNF alpha. Inhibition of protein synthesis by cycloheximide as well as addition of cyclic adenosine monophosphate synergistically enhanced the suppression of mitochondrial respiration by TNF alpha, resulting in complex I activity of 6.9 +/- 1.6% and 24.9 +/- 2.9% of that of untreated cells. These data indicate that inhibition of mitochondrial respiration is one of the mechanisms by which TNF alpha induces tissue injury. PMID- 1444646 TI - Rapid increase in plasma levels of atrial natriuretic peptide after common bile duct ligation in the rabbit. AB - Previous studies have shown that common bile duct ligation in the rabbit is followed by a reduction of the extracellular water compartment. To further elucidate the mechanisms leading to volume depletion in this model, water and sodium balances and changes in plasma concentrations of atrial natriuretic peptide (ANP), vasopressin (ADH), plasma renin activity (PRA) and aldosterone (Ald) were investigated during the first 4 days after common bile duct ligation (group OJ,) or sham operation (group SO). Water and chow intakes were lower in group OJ (148 +/- 30 versus 226 +/- 40 mL/4 days; p = 0.004 and 12 +/- 9 versus 171 +/- 40 g/4 days; p = 0.0001). There were no differences in urine output. Sodium urinary losses were marginally higher in group OJ (12.4 +/- 7 versus 6.7 +/- 5 mEq/4 days; p = 0.06). Water balance was lower in group OJ (-50 +/- 56 versus 101 +/- 71 mL/4 days; p = 0.0001). At 24 hours, plasma ANP (41 +/- 7 versus 10.7 +/- 1 fmol/mL, p = 0.0001), ADH (21.8 +/- 7 versus 12.3 +/- 6 pg/mL, p = 0.008) and Ald (14.5 +/- 5 versus 3.7 +/- 3 ng/dL, p = 0.001) were higher in group OJ. These alterations persisted 72 hours after bile duct ligation, when a concomitant increase in PRA (10.7 +/- 5 versus 3 +/- 1.6 ng/dL, p = 0.006) was also observed. A group of pair-fed pair-watered sham-operated controls (group SO2, n = 13) showed a metabolic profile similar to group OJ but a low ANP concentration. Multiple venous sampling in five rabbits 24 hours after bile duct ligation showed the highest plasma levels of ANP in the aorta and infrarenal vena cava. These results suggest that common bile duct ligation in the rabbit is followed by marked hypodipsia and hypophagia, possibly mediated by ANP, leading to isotonic volume depletion and secondary activation of the water and sodium retaining hormones. PMID- 1444647 TI - Immunohistochemical characteristics of human milk-fat globule antibodies in predicting chest wall and distant metastasis after mastectomy for localized cancer of the breast. AB - Because postoperative radiation reduces chest wall metastasis after mastectomy, it is important to identify patients in whom it might develop. Pathologic and immunohistochemical features in 59 patients with chest wall metastasis were compared with characteristics in disease-free patients and patients with systemic metastases without chest wall metastasis. Immunohistochemical studies with human milk-fat globule (HMFG)-2 were not predictive, but a membrane reaction with HMFG 1 was associated with fewer systemic metastases and tumors, in which most of the cells reacted with the antibody had significantly decreased likelihood of chest wall metastasis. Antigenic concordance between the primary breast cancer and the chest wall metastasis was demonstrated. Neither tumor size nor axillary node metastasis predicted development of chest wall metastasis, but systemic metastases were less common when fewer than four nodes were involved, the primary tumor was well differentiated, and estrogen receptors were positive. PMID- 1444648 TI - Congenital diaphragmatic hernia. Stabilization and repair on ECMO. AB - Availability of extracorporeal membrane oxygenation (ECMO) support and the potential advantages of delayed repair of congenital diaphragmatic hernia (CDH) have led several centers to delay CDH repair, using ECMO support if necessary. This study reviews the combined experience of five ECMO centers with infants who underwent stabilization with ECMO and repair of CDH while still on ECMO. All infants were symptomatic at birth, with a mean arterial oxygen pressure (PaO2) of 34 mmHg on institution of bypass despite maximal ventilatory support. A total of 42 infants were repaired on ECMO, with 18 (43%) surviving. Seven infants had total absence of the diaphragm, and 28 required a prosthetic patch to close the defect. Only five infants ever achieved a best postductal PaO2 over 100 mmHg before institution of ECMO. Prematurity was a significant risk factor, with no infants younger than 37 weeks of age surviving. Significant hemorrhage on bypass was also a hallmark of a poor outcome, with 10 of the 24 nonsurvivors requiring five thoracotomies and six laparotomies to control bleeding, whereas only one survivor required a thoracotomy to control bleeding. In follow-up, nine of the 18 survivors (50%) have developed recurrent herniation and seven (43%) have significant gastroesophageal reflux. Importantly, five of the 18 survivors were in the extremely high-risk group who never achieved a PaO2 over 100 mmHg or an arterial carbon dioxide pressure (PaCO2) less than 40 mmHg before the institution of ECMO. In conclusion, preoperative stabilization with ECMO and repair on bypass may allow some high-risk infants to survive. Surviving infants will require long term follow-up because many will require secondary operations. PMID- 1444649 TI - The effect of pancreatic polypeptide on glucose disposal after surgical alterations of the pancreas. AB - Surgical alterations of the pancreas result in anatomic changes that can affect postoperative glucose metabolism. Pancreas transplantation results in reduction of beta-cell mass, systemic release of insulin, and denervation. The authors hypothesized that such alterations affect peripheral glucose disposal to induce an "insensitivity" to endogenously (systemically) released insulin. Additionally, they hypothesized that surgically induced deficiency of the postprandial hormone, pancreatic polypeptide, might contribute to altered glucose disposal. The authors studied two surgical models in dogs known to be devoid of pancreatic polypeptide- 70% proximal pancreatectomy (PPx) and PPx plus distal pancreas autotransplantation (PAT/B). Oral glucose challenge and euglycemic hyperinsulinemic clamp studies were performed before and after a 16-day "pulsed" infusion of pancreatic polypeptide. Both surgical procedures resulted in elevations in the integrated glucose response after oral glucose, which was not affected by pancreatic polypeptide infusion. Euglycemic clamp studies showed decreased hepatic glucose output (Ra) and overall glucose disposal (Rd) in the fasted state for both surgical groups. The transplant animals demonstrated significant decreases in Rd during the hyperinsulinemic challenge (3.2 +/- 0.01 versus 5.7 +/- 0.01 mg/kg/minute at 60 to 120 minutes for PAT/B versus control). After 16 days of pancreatic polypeptide infusion, however, basal Ra, as well as basal and 60- to 120-minute Rd values, were returned to control values in the transplant group. The authors conclude that pancreas transplantation results in altered glucose disposal, possibly due to an altered effectiveness of systemically released insulin. They conclude that pancreatic polypeptide is an important modulator of peripheral insulin action. Therefore, the role of pancreatic polypeptide must be taken into account when evaluating postoperative glucose metabolism in canine models of pancreas transplantation. PMID- 1444650 TI - Surgical strategies in esophageal carcinoma with emphasis on radical lymphadenectomy. AB - From 1975 through 1988, 257 patients with carcinoma of the thoracic esophagus have been treated in our department. Operability was 90% (232/257); overall resectability, 77% (198/257), and for the operated group, 85% (198/232). Hospital mortality rate was 9.6% but decreased to 3% over the period 1986 to 1988. There were 65% squamous cell epitheliomas and 35% adenocarcinomas. Tumor, nodes, and metastases (pTNM) staging was as follows: stage I, 11.6%; stage II, 23.2%; stage III, 37.9%; stage IV, 27.3%. Overall survival rate was 62.5% at 1 year, 42.4% at 2 years, and 30% at 5 years. According to the pTNM staging, 5-year survival was 90% for stage I, 56% for stage II, 15.3% for stage III, and 0 for stage IV. There were no statistically significant differences according to tumor localization, pathologic type, sex, or age. Introducing extensive resection and extended lymphadenectomy seems to improve significantly survival in patients in whom an operation with curative intention was performed, the 1 year survival rate being 90.8% versus 72%; 2-year survival, 81% versus 46%; and 5-year survival, 48.5% versus 41% for radical and nonradical resections, respectively. Based on multivariate Cox regression analysis, only TNM stage and presence or absence of lymph nodes are important factors in predicting survival: stage 1 tumors have lower risk, and involvement of lymph nodes creates higher risk. Using this analysis, there was only for the patients with involved lymph nodes (N1) a significantly better prognosis when a radical lymph node dissection was performed (p = 0.0055). Barrett adenocarcinomas have no worse prognosis than other esophageal carcinomas, with a 5-year survival rate of 91.5% if lymph nodes are negative, and a 54% overall 5-year survival rate. Functional results after restoration of continuity with gastric tubulation were judged excellent to very good in 86.5% at 1 year, but infra-aortic anastomoses have a much higher incidence of peptic esophagitis: 53% versus 8% for cervical anastomoses. From this study it can be concluded that in experienced hands surgery today offers the best chances for optimal staging, potential cure, and prolonged high-quality palliation. PMID- 1444651 TI - Vascularized tissue transfer for closure of irradiated wounds after soft tissue sarcoma resection. AB - During the years 1985 to 1989, 82 patients were included in the soft tissue sarcoma protocol. Preoperative irradiation (50-54 Gy) was performed in all patients before tumor extirpation. Microwave hyperthermia was performed in conjunction with radiation in patients who had gross tumor remaining after initial biopsy. Primary closure with vascularized tissue (flaps) in lieu of conventional wound closure by skin approximation led to less complications (19% versus 51%), fewer secondary procedures for wound closure (10% versus 35%), shorter average hospitalization (15 versus 48 days) and greater limb salvage rate (97% versus 91%). The authors conclude that vascularized tissue (flaps) for primary wound closure in irradiated tissue leads to improved wound healing, and should be considered the procedure of choice for heavily irradiated soft tissue sarcoma defects. PMID- 1444652 TI - A prospective evaluation of plasma-TFE and expanded PTFE grafts for routine and early use as vascular access during hemodialysis. AB - The use of prosthetic grafts as vascular access for chronic hemodialysis is frequently necessary in patients with end-stage renal disease. Most commonly, expanded polytetrafluoroethylene (e-PTFE) has been employed because of ease of handling, tissue inertness, and acceptable long-term patency. Delay in use to allow for tissue ingrowth, however, has often required placement of temporary access devices. The authors have undertaken evaluation of a new material, plasma polymerized woven dacron Plasma-TFE, in a prospective randomized trial (Plasma TFE VA) to compare clinical behavior against e-PTFE grafts, and we have used the Plasma-TFE grafts in an additional group of patients (Plasma-TFE AVA) as early access (within 1 week of implantation). Twenty-one Plasma-TFE grafts were implanted in 19 patients and 19 e-PTFE grafts were implanted in 17 patients in a prospective randomized fashion. Additionally, 31 Plasma-TFE grafts were implanted in 31 nonrandomized patients for early access. Primary patency rates in Plasma TFE VA and e-PTFE grafts were equivalent at 12 months (0.471 and 0.556). When Plasma-TFE AVA primary patency was included (0.621), comparisons were not statistically significant (p = 0.50). Similarly, secondary patency rates among the three groups did not differ (cumulative proportion patent at 12 months: Plasma-TFE VA 0.403, e-PTFE 0.658, Plasma-TFE AVA 0.510). In considering after revision patency after graft thrombosis, however, the Plasma-TFE grafts (both VA and AVA) performed significantly more poorly (p = 0.027) than e-PTFE grafts. Incidence of graft infection, wound infection, arm edema, hematoma from use, and occurrence of distal limb ischemia between Plasma-TFE (VA and AVA) and e-PTFE did not differ statistically. The authors conclude that Plasma-TFE compares favorably to e-PTFE with respect to primary and secondary patency and nonthrombotic complications, even with early use. Plasma-TFE does not perform as well as e PTFE, however, after graft thrombosis. PMID- 1444653 TI - Logistics and technique for combined hepatic-intestinal retrieval. AB - During a 13-month period, en bloc liver-small bowel cadaveric grafts were procured for seven children and one adult. All liver grafts functioned immediately, and all but one of the recipient patients recovered. Return of absorptive small bowel function was slow, but the integrity of the bacterial intestinal barrier was not disrupted. The described technique allows the procurement of other abdominothoracic organs, with the exception of the whole pancreas. PMID- 1444654 TI - Sex differences in gallstone pancreatitis. PMID- 1444655 TI - Brachytherapy enhanced the local control of soft-tissue sarcomas, but failed to enhance survival. PMID- 1444656 TI - Comparison of amputation with limb-sparing operations for adult soft tissue sarcoma of the extremity. PMID- 1444657 TI - Human liver regeneration after major hepatectomy. PMID- 1444658 TI - [The development of bacterial resistance and the role of clavulanic acid]. PMID- 1444659 TI - [Changes in the bacterial resistance to beta-lactam antibiotics and the ways to overcome it]. PMID- 1444660 TI - [Augmentin: the world-wide experience in its clinical use]. PMID- 1444661 TI - [The treatment of severe infections]. PMID- 1444662 TI - [The pharmacokinetics, dosage, tolerance, side effects and safety of the preparation Augmentin (a combination of amoxicillin and clavulanic acid)]. PMID- 1444663 TI - [The efficacy of Augmentin in suppurative complications in neurosurgery]. AB - The results of clinical and laboratory studies on the use of augmentin in severe purulent complications after neurosurgical operations are presented. The laboratory studies carried out with the use of an automatic system Cobas Bact (Roch) showed that the numbers of the augmentin resistant strains of Staphylococcus and Enterobacteriaceae among the pathogens were 47 and an average of 64.5%, respectively. Gram-negative bacteria resistant to augmentin were 1.5 to 2 times less frequent than those resistant to amoxycillin. Still, they were much more frequent than those resistant to cefotaxime and ceftriaxone. Clinical efficacy of augmentin was studied in treatment of 39 patients with various affections of the brain such as tumors, trauma, vascular malformations and inflammatory processes. The postoperative complications were represented by meningitis, pneumonia, sepsis and their associations. The use of augmentin in the severe intra- and extracranial complications was favourable in 82.1% of the cases. PMID- 1444664 TI - [Augmentin in the clinical picture of infectious diseases]. AB - Augmentin is a new combination manufactured by Smith Kline Beecham (Great Britain). It is composed of amoxycillin and clavulanic acid and has antibacterial activity. Augmentin was used in clinical trials in the therapy of 50 adult patients with suppurations after surgical operations on the organs of the abdominal cavity, general staphylococcal infections, pneumonia and prophylactically during the preoperative period. It was also used in the treatment of 30 children patients with bronchopulmonary affections and inflammatory otorhinolaryngological diseases. The clinical trials were performed in the Clinic of Infectious Diseases of the N. G. Gabrichevskii Moscow Research Institute of Epidemiology and Microbiology. For comparison ampicillin was used in the trials. Augmentin was shown to be an efficient formulation with antibacterial activity which could be successfully used in the parenteral therapy of severe affections due to organisms sensitive to it. In the treatment of the children patients with pneumonia augmentin by its therapeutic efficacy proved to be superior to ampicillin. The tolerance of augmentin was good. PMID- 1444665 TI - [Augmentin in the combined therapy of puerperal diseases]. AB - Augmentin was used in treatment of mild forms of postnatal endometritis and serous mastitis. Augmentin tablets proved to be efficient in endometritis due to enterobacteria and obligate nonsporulating anaerobes and mastitis due to Staphylococcus aureus strains sensitive to the preparation. No adverse events were recorded. It was shown that in the treatment of mild postnatal infections the augmentin tablets were not inferior by their activity of combinations of antibiotics against aerobic and anaerobic microflora. PMID- 1444666 TI - [A clinico-laboratory assessment of the efficacy of an Augmentin suspension in treating children with suppurative-inflammatory diseases caused by opportunistic bacteria]. AB - Augmentin suspension (amoxycillin+clavulanic acid) was estimated in clinico laboratory studies with respect to children suffering from pyoinflammatory diseases of various localization and its high efficacy was shown. Good and satisfactory results were recorded in 96.3 per cent of the cases in the treatment (monotherapy) and afterwards in the patients, adverse reactions such as nausea and vomiting being recorded only in 1 patient. The therapy with augmentin led to normalization of the microflora of the upper respiratory tract mucosa and a 1.5 fold increase in the neutrophil engulfment index. PMID- 1444667 TI - [Augmentin]. PMID- 1444668 TI - [The efficacy of Augmentin in treating gonorrheal infection]. PMID- 1444669 TI - [The antimicrobial activity of Augmentin (amoxicillin/clavulanic acid) compared to other antibacterial agents]. AB - Sensitivity of clinical strains of gram-positive and gram-negative bacteria to Augmentin was studied in comparison to other antibiotics. Augmentin was shown to be advantageous in the level and spectrum of its antibacterial activity over ampicillin and other broad-spectrum antibiotics. PMID- 1444670 TI - [A comparative analysis of the immunochemical determination of gentamycin by fluorescence polarization and quenching]. AB - A polarization fluorescence immunoassay (PFIA) for gentamicin with using a set of reagents made in this country was developed. One ml of fluorescein-labeled gentamicin (50 nM) and 100 microliters of antiserum are added to 50 microliters of the sample and the fluorescence polarization is measured. The time of the assay is 10 to 15 minutes, the range of the measurable concentrations is 0 to 800 ng/ml, the sensitivity of the method is 5 ng/ml and the accuracy is 5.8-10.3 per cent. A fluorescence quenching immunoassay (FQIA) for gentamicin was also developed. Determination of gentamicin by the FQIA does not require the use of a specific polarization fluorimeter. Its linear calibrating dependence is more convenient. However, its accuracy and sensitivity are 3 times lower than those of the PFIA. PMID- 1444671 TI - [The clinical significance and methodological problems in determining bacterial sensitivity/resistance to antiseptics]. PMID- 1444672 TI - [The theoretical and practical aspects of the problem of antibiotic resistance]. PMID- 1444673 TI - [The effect of the pathogenetic characteristics of an infection on the efficacy of chemotherapy]. PMID- 1444674 TI - [Comparative research on Augmentin]. PMID- 1444675 TI - Cardiopulmonary resuscitation in chronically ill patients in the intensive care unit. Does poor outcome justify withholding cardiopulmonary resuscitation from this group? PMID- 1444676 TI - Living with Hippocrates in a changing medical world, with particular reference to the patient-physician relationship. PMID- 1444677 TI - The rationale of magnesium supplementation in acute myocardial infarction. A review of the literature. PMID- 1444678 TI - Blue toe syndrome. Causes and management. AB - The sudden development of cyanotic lesions on the feet may be a result of atheroembolic disease or a number of medical conditions. A careful history and physical examination, basic laboratory tests, and noninvasive vascular assessment usually distinguish between medical and surgical causes and direct the choice of further investigations. Specific therapy is often available for medical conditions causing this syndrome. The management of atheroembolic disease is more controversial. In particular, further research is necessary to determine which patients need surgical intervention and which patients can be managed safely by medical therapy. PMID- 1444679 TI - Physical restraints in the practice of medicine. Current concepts. AB - OBJECTIVE: This article reviews the current status of the utilization of physical restraints in the practice of medicine. Based on current data from the reference sources, appropriate guidelines for the utilization of physical restraints in the practice of medicine are presented. DATA SOURCES: A review of the current literature as referenced in the article. Only English-language references were used. STUDY DESIGN: Articles were selected based on a review of articles from Index Medicus, English-language only. Articles were reviewed by the author for validity and appropriateness. DATA EXTRACTION: The guidelines of data quality, validity, and appropriateness were applied to all articles by the author. DATA SYNTHESIS: Restraints are frequently used in the practice of medicine. As many as 85% of nursing home patients will be restrained at some time and up to 17% of hospitalized medical patients will be restrained. This treatment is not always appropriate but there are no current guidelines available for the practicing physician to assist him or her in these decisions. The current use of physical restraints is discussed. The risks of restraints are reviewed and the reasons for restraint use are cited. The question regarding the efficacy of restraints is directly addressed for each of the situations in which restraints are most commonly used. The ethical and legal considerations concerning the use of restraints are reviewed, current concepts are summarized, and guidelines for improved usage of restraints are suggested. CONCLUSIONS: Despite their extensive use, there is virtually no evidence to support the efficacy of restraints. The risks of using mechanical restraints are numerous and well documented. The detrimental psychologic impact of restraints needs to be emphasized. Restraints are inappropriately used if employed because of fear of liability should a patient fall. The proper approach to the patient at risk of falling is to address the contributing factors that place the patient at risk and, where possible, correct them. Restraints are overused in medicine. Guidelines are given to help improve the employment of this potentially harmful practice. PMID- 1444680 TI - Resource utilization among intensive care patients. Managed care vs traditional insurance. AB - BACKGROUND: There is considerable evidence that members of managed care organizations use fewer hospital resources than patients covered by traditional health insurance. While intensive care might seem to be an unlikely setting for such differences to exist, the relationship between health coverage and use of intensive care has not been examined. METHODS: We conducted a cross-sectional analysis of consecutive intensive care unit admissions at a regional tertiary care teaching hospital. Patients in managed care plans (n = 159) and with traditional insurance (n = 389) were compared with respect to length of stay, hospital charges, charges for specific services, and use of mechanical ventilation. The analysis controlled for severity of illness, as measured by the Mortality Probability Model, case mix, and mortality. The whole sample as well as subsamples representing medical, emergency surgery, and elective surgery patients were examined. RESULTS: The managed care group, on average, had short stays (both hospital and intensive care unit), lower charges, and less use of mechanical ventilation than the traditionally insured group. Average differences of about 30% to 40% were observed. The finding held for the whole sample as well as the medical and emergency surgery subsamples. The differences were more pronounced in the patients with lowest severity of illness. CONCLUSION: Even in a setting where there would appear to be relatively little room for discretion in treatment decisions, incentives associated with type of health insurance seemed to affect resource use. PMID- 1444681 TI - From data to policy ... to politics. The Minnesotans health care plan for universal access to care. AB - Calls for major reform of the health care delivery system have been sounded at both the state and federal level. However, given the lack of consensus on health care reform at a federal level, more than half of the states are developing initiatives for universal access to care. In 1989, the Minnesota legislature created the Health Care Access Commission to develop a blueprint for universal access in Minnesota. To assist this effort, we studied the extent and nature of uninsurance and underinsurance within the state. In this article we report the findings of that study and discuss how the findings were first used to develop recommendations for universal access legislation. We then describe the fate of the legislation. Finally, we describe the veto and the creation of HealthRight, the recently enacted plan for health care reform bill in Minnesota. This plan simultaneously expands access to care and aims to contain health care costs. PMID- 1444682 TI - Screening women of childbearing age for human immunodeficiency virus. A cost benefit analysis. AB - In light of the increasing problem of perinatal human immunodeficiency virus (HIV) transmission, the issue of screening women for HIV is receiving considerable attention. We analyzed the costs and benefits of screening women of childbearing age for HIV. The analysis was based on a dynamic model of the HIV epidemic that incorporated disease transmission and progression, behavioral changes, and effects of screening and counseling. We found that the primary benefit of screening programs targeted to women of childbearing age lies not in the prevention of HIV infection in their newborns but in the prevention of infection in their adult contacts. Because of this benefit, screening medium- and high-risk women is likely to be cost-beneficial over a wide range of assumptions about program cost and behavioral changes in response to screening. PMID- 1444683 TI - Physicians' attitudes toward mandatory workplace urine drug testing. AB - BACKGROUND: Workplace drug testing programs are being increasingly implemented in both the public and private sectors, and health care workers are unlikely to be excluded from such testing. METHODS: A survey of attending physicians' attitudes toward mandatory hospital-based urine drug testing was undertaken in a medium sized, midwestern county. RESULTS: Seventy-four percent (272/368) of the sample responded. Seventy-two percent of the subjects believed physician drug use to be a minor or nonexistent problem, 38% lacked confidence in the testing procedure, and 60% believed that testing infringed on the physician's right to privacy; yet 87% would submit to testing if required by a hospital. Forty-five percent of respondents agreed with the policy of mandatory testing for physicians with hospital privileges, 34% disagreed, and 21% were uncertain. Respondents were more supportive of mandatory testing of other health care and non-health care occupations than for themselves. Support for testing was greatest for illicit drugs. If implemented, physicians preferred mandatory testing to be performed by hospital medical staff independent of hospital administration. CONCLUSIONS: Further education and discussion within the physician community appears to be necessary before widespread mandatory workplace urine drug testing of physicians is implemented. PMID- 1444684 TI - Dialysis support of patients with primary systemic amyloidosis. A study of 211 patients. AB - BACKGROUND: The study assessed dialysis support in patients with primary systemic amyloidosis without associated multiple myeloma in whom renal insufficiency developed. METHODS: The study group consisted of 211 patients with biopsy-proved primary systemic amyloidosis examined at the Mayo Clinic, Rochester, Minn. No patient was lost to follow-up. RESULTS: Thirty-seven (18%) of the patients received dialysis therapy. Of those presenting with renal amyloid, one third received dialysis. The median time from diagnosis to initiation of dialysis was 13.8 months. The median survival for patients from the start of dialysis was 8.2 months. There was no survival difference between hemodialysis (n = 27) and peritoneal dialysis (n = 10). The most important predictors of which patients would ultimately require dialysis were the 24-hour urinary protein loss and serum creatinine values at the time amyloidosis was diagnosed. None of the patients seen at diagnosis with a normal serum creatinine value and proteinuria of less than 2 g/d required dialysis during follow-up. Of the 37 patients who received dialysis, 31 died, and 21 of the 31 died as a result of extrarenal progression of their systemic amyloidosis. Fifteen of the 31 deaths were a result of cardiac amyloidosis. All long-term survivors had normal echocardiograms without evidence of amyloid. CONCLUSION: Eighteen percent of patients with primary amyloidosis undergo dialysis. The 24-hour urinary protein loss and creatinine values are helpful in predicting which patients eventually will require dialysis. The median survival for patients starting dialysis is less than 1 year. Patients whose two dimensional echocardiograms are normal are most likely to derive long-term benefit from dialysis. PMID- 1444685 TI - Occupation and risk of nonfatal myocardial infarction. AB - BACKGROUND: While some analytic studies have suggested that individuals in occupations representing higher compared with lower socioeconomic status have a decreased risk of coronary heart disease, it is unclear whether occupation itself has an etiologic role in the development of coronary heart disease or whether differences in as yet uncontrolled coronary risk factors may account for these differences in risk. METHODS: White-collar vs blue-collar occupation and risk of coronary heart disease was evaluated among 230 male patients hospitalized for a first myocardial infarction and 222 control subjects of the same age, sex, and neighborhood of residence. Information on coronary risk factors was obtained from home interviews, and blood specimens were drawn to test lipid and lipoprotein levels. Usual occupation was dichotomized into white-collar and blue-collar occupation according to the Edwards' classification. RESULTS: The relative risk of myocardial infarction of white-collar compared with blue-collar workers was 0.74 (95% confidence interval, 0.46 to 1.19) after controlling for age, cigarette smoking, family history of premature myocardial infarction, history of treatment for high blood pressure, body mass index, history of diabetes, alcohol consumption, type A personality, leisure-time physical activity, total calories, and percentage of calories consumed as saturated fat. However, there was no residual association after control for high-density lipoprotein cholesterol yielding a relative risk of 0.98 (95% confidence interval, 0.59 to 1.63). CONCLUSIONS: These results suggest that white-collar occupation per se does not appear to protect from coronary heart disease. Any apparent protective effect on myocardial infarction that has been previously observed in white-collar compared with blue-collar workers may be attributable to differences in high-density lipoprotein cholesterol levels. PMID- 1444686 TI - Lack of age-related differences in the clinical presentation of digoxin toxicity. AB - BACKGROUND: Digoxin toxicity occurs most commonly among the elderly. While the clinical syndrome of digoxin toxicity is well understood, how toxic manifestations change with age is not known. METHODS: We performed secondary analysis of data from a postmarketing surveillance study of patients with life threatening digoxin toxicity treated with digoxin antibody therapy. Patients receiving long-term maintenance digoxin therapy and aged 55 years or older were divided into four age groups: 55 to 64, 65 to 74, 75 to 84, and 85 years and older (n = 45, 167, 183, and 83, respectively) and compared with regard to presenting manifestations, digoxin dosing, serum potassium and digoxin levels, and renal function. RESULTS: The prevalence of high-degree atrioventricular block showed an increasing but nonsignificant trend with age (40%, 40%, 42%, and 47%, respectively). Age-related trends in high-degree atrioventricular block were stronger among men than women and even stronger among men with underlying cardiac ischemia. The proportion of subjects with nausea/vomiting as a toxic manifestation did not consistently change with age (42%, 48%, 48%, and 46%, respectively). There were no age-related differences in degree of renal impairment or maintenance dose, but maintenance dose decreased with increasing renal impairment. CONCLUSIONS: Among patients with life-threatening digoxin toxicity, there is no age-related difference in clinical presentation. PMID- 1444687 TI - Risk of age-related fractures in patients with primary hyperparathyroidism. AB - BACKGROUND: Bone mass is reduced, but the influence of primary hyperparathyroidism (HPT) on fracture risk is controversial. We addressed this issue in a population-based retrospective cohort study. METHODS: Ninety residents of Rochester, Minn, were first diagnosed with HPT in 1965 through 1976 and an equal number of age- and sex-matched control subjects from the community were identified. Fractures were assessed through review of each subject's complete (inpatient and outpatient) medical records in the community. RESULTS: Prior to the date of diagnosis, Rochester residents with HPT were more likely to have a history of fractures than were matched control subjects from the same population (30% vs 18%). Subsequently, 36% of cases and 31% of control subjects experienced one or more new fractures during 1072 person-years of follow-up; survival free of a new fracture was almost the same in the two groups. Women had more fractures than men, and fracture rates increased with age. Fractures appeared to be somewhat more frequent in those with baseline serum calcium levels of 2.74 mmol/L or more, in those with comorbid conditions possibly due to HPT and in those who did not undergo parathyroidectomy, but these differences were not statistically significant. In a multivariate analysis, only age at diagnosis was an independent predictor of fracture risk, with a 36% increase in risk per 10-year increase in age. CONCLUSIONS: Overall fracture risk was increased prior to diagnosis of HPT but not afterward. Because the numbers involved were small, however, we cannot exclude an increased likelihood of fractures in certain subgroups of HPT patients. PMID- 1444688 TI - High incidence rates of invasive pneumococcal disease in the White Mountain Apache population. AB - OBJECTIVE: In this article we determine the incidence and clinical spectrum of invasive pneumococcal disease in the White Mountain Apache population, a group known to have a high incidence of invasive disease due to Haemophilus influenzae type b. DESIGN: Patients from whom cultures of normally sterile body sites yielded Streptococcus pneumoniae were identified retrospectively through review of hospital laboratory records from a 6.8-year period. Clinical data were reviewed and incidence rates were computed. SETTING: The Whiteriver Indian Health Service Hospital is located on the 1.7-million-acre White Mountain Apache Reservation in eastern Arizona. PATIENTS: Approximately 10,000 members of the White Mountain Apache Tribe reside on or near the reservation and receive health care through the Whiteriver Indian Health Service Hospital. OUTCOME MEASURES: The average annual incidence rates of invasive pneumococcal disease were calculated and clinical characteristics were reviewed. RESULTS: One hundred thirty-eight cases of invasive pneumococcal disease were identified. The average annual incidence rate was 207 per 100,000 population, and 156 per 100,000 population when adjusted for age by direct standardization to the 1988 US population. The incidence rate was highest in children between 1 and 2 years--2396 per 100,000. The overall case-fatality rate was 5%. Pneumococcal pneumonia was the diagnosis in 79% of the patients 5 years of age or older. Alcohol abuse, identified in 66% of the cases in adults, was the most common underlying medical condition. CONCLUSION: The incidence rates in White Mountain Apaches are the highest reported for any population. A vaccine effective in children would greatly benefit this population. PMID- 1444689 TI - Acquired immunodeficiency syndrome/human immunodeficiency virus risk behavior among gay men in small cities. Findings of a 16-city national sample. AB - BACKGROUND: Most research on acquired immunodeficiency syndrome has been conducted in several of the country's largest cities, and little is known about the current level of human immunodeficiency virus risk taking among gay men in other geographical areas. The purpose of this study was to determine the frequency of risk behavior practices among gay men in smaller communities. METHOD: A large sample of men who patronized gay bars in 16 small and moderate size cities drawn from six states in four different regions of the country was surveyed to determine the frequency of high-risk behavior and factors influencing risk taking. Eighty-five percent of men in all cities' bars completed all survey measures. The community samples were 1991 men; mean age, 31.3 years; mean education, 10.6 years; 90% were white and 10% were of other ethnicities. All participants provided detailed information on their sexual behavior practices over the preceding 2 months and completed measures assessing their perceived peer norms concerning safer sex practices and risk avoidance, intentions to avoid risk, personal risk estimation, acquired immunodeficiency syndrome risk knowledge, perceived threat of acquired immunodeficiency syndrome/human immunodeficiency virus, and serostatus testing history. RESULTS: High-risk patterns were still common among gay men in these smaller cities; nearly one third of all men had engaged in unprotected anal intercourse an average of eight times in the past 2 months, usually outside monogamous relationships. High-risk behavior was most strongly associated with beliefs that safer sex practices would not be well accepted by peers, weak intentions to use condoms, underestimation of personal vulnerability to the acquired immunodeficiency syndrome, younger age, and higher levels of overall sexual activity. Nine percent of men tested said they were seropositive. CONCLUSIONS: Growing human immunodeficiency virus prevalence and continued high rates of risk behavior indicate that a new "front line" for human immunodeficiency virus prevention among homosexually active men has shifted to the country's smaller cities. Community prevention efforts in these areas are urgently needed to avert sharp increases in future human immunodeficiency virus infections in this population. PMID- 1444690 TI - Purulent otitis media in adults. AB - While the bacterial origin of otitis media has been studied extensively in children, there are few data regarding adults with this disease. We undertook this study to identify the incidence, prevalence, and bacteriologic origin of purulent otitis media in adults. This was accomplished through a review of the English-language literature on adult otitis media and a retrospective review of adult patients with this disease who were hospitalized at our institution. Results of literature review indicate that Streptococcus pneumoniae and Haemophilus influenzae are the most common causes of otitis media in ambulatory adults, but this illness is uncommon, with an incidence of only 0.25%. Hospitalized patients in whom this diagnosis was established suffered a variety of serious suppurative complications such as mastoiditis, meningitis, or brain abscess. Otalgia and fever were the most common symptoms noted in this patient population. Further studies of adult otitis media need to be performed to determine bacteriologic, symptomatic, and high-risk patient groups. PMID- 1444691 TI - Outcome of cardiopulmonary resuscitation in the intensive care setting. AB - BACKGROUND: Although cardiopulmonary resuscitation (CPR) has been shown to be most effective in a monitored setting, previous studies have focused primarily on patients with acute cardiac events rather than chronic progressive disease. This study examined the outcome of CPR in the medical and surgical intensive care units where patients often have acute illness superimposed on chronic underlying conditions. METHODS: We present a retrospective chart review of all patients undergoing CPR in medical and surgical intensive care units during a 2-year period. RESULTS: One hundred fourteen charts were reviewed. Patient mean age was 59 years. The primary underlying disease was malignancy in 29 (25%), vascular disease in 20 (18%), chronic liver disease in eight (7%), end-stage renal disease in six (5%), chronic obstructive pulmonary disease in five (5%), and other conditions in 46 (40%) patients. Although 50 (44%) of the patients were initially resuscitated, only six (5%) ultimately survived to hospital discharge. Only one of 29 patients with malignancy and one of 39 septic patients survived. Age, sex, and Acute Physiology and Chronic Health Evaluation II scores were similar among survivors and nonsurvivors. Furthermore, four of the six survivors died within 1 year of discharge, and the two others had severe disabilities. CONCLUSIONS: Patients with chronic medical conditions undergoing CPR even in an intensive care unit setting seldom survive to hospital discharge. Even among the few survivors, the near term prognosis is poor. Therefore, the decision to perform CPR should take into account underlying chronic medical conditions and not merely the setting of the arrest. PMID- 1444692 TI - Life-sustaining interventions in frail elderly persons. Talking about choices. AB - BACKGROUND: Engaging older persons in consideration of use of life-sustaining measures, such as cardiopulmonary resuscitation, tube feeding, and urgent intubation, is widely recommended, yet uncommon. METHODS: We studied the short term impact of a physician-initiated discussion, geared toward guiding informed decision-making, with 20 frail elderly homebound patients. A battery of psychologic rating scales was administered in a pre-post design. Eighteen subjects completed the protocol. Fifteen of the mentally capable surviving subjects were reinterviewed 18 months following the initial discussion to evaluate durability of their decisions. RESULTS: Most welcomed the discussion and clear choices regarding future care usually emerged. Depression rating scales decreased slightly for the entire sample. For the subgroup having relatively internal locus of control, there was an increase in life satisfaction scores. No patient demonstrated signs of emotional trauma consequent to the discussion. On follow-up, several patients were indecisive about their choices. CONCLUSION: Involvement of these patients in decision-making appeared to have no adverse effects, and, for some, it was therapeutic, possibly through enhancement of personal control. Durability of their decisions was not a consistent finding, however. PMID- 1444693 TI - Ranitidine pharmacokinetics and adverse central nervous system reactions. AB - BACKGROUND: Treatment with histamine2-receptor antagonists has been associated with adverse central nervous system reactions (CNS-ADRs). Previous studies of cimetidine have shown an association between CNS-ADRs and high cimetidine drug levels. While case reports of ranitidine CNS-ADRs have appeared, we wanted to study a series of patients, some of whom were critically ill, for the presence of CNS-ADRs and to correlate these with ranitidine pharmacokinetics. METHODS: A prospective, observational, open study included 163 consecutive patients, of whom 41 met entry criteria. A nonlinear least-squares regression analysis was used to establish a ranitidine pharmacokinetic dosing model. Ranitidine levels were determined by a high-performance liquid chromatographic assay. Individual ranitidine pharmacokinetics were determined by means of a bayesian model. Observations on 13 possible CNS-ADRs were recorded. The CNS-ADRs were evaluated by the Naranjo rating system. RESULTS: Ranitidine-associated CNS-ADRs, particularly lethargy, confusion, somnolence, and disorientation, occurred more frequently in patients with renal function impairment, and these were associated with higher peak concentrations, average plasma concentrations, and area under the curve. CONCLUSIONS: Ranitidine, when given in conventional doses, can cause CNS-ADRs, particularly in older patients who have substantial renal function impairment. These CNS-ADRs occur as a consequence of altered ranitidine disposition. Ranitidine doses should be reduced when renal function impairment is present, and patients should be carefully observed for CNS-ADRs. PMID- 1444694 TI - Biguanide-associated lactic acidosis. Case report and review of the literature. AB - PURPOSE: The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis. PATIENT: We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia. RESULTS: Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital. CONCLUSIONS: Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications. PMID- 1444695 TI - 'Diaphragmlike' stricture and ulcer of the colon during diclofenac treatment. AB - Diclofenac sodium is a widely used enteric-coated nonsteroidal anti-inflammatory drug. We describe a woman with Hemoccult-positive stools and iron deficiency anemia who developed both a colonic ulcer and a "diaphragm-like" colonic stricture while taking enteric-coated diclofenac. These lesions were evident on colonoscopy but not on barium studies. Biopsy specimens of the ulcer and stricture revealed particulate matter that was indistinguishable from diclofenac pill fragments by electron microscopy. Discontinuation of diclofenac therapy resulted in resolution of anemia and Hemoccult-positive stools. We conclude that (1) enteric-coated diclofenac is associated with both colonic ulcers and diaphragm-like colonic strictures; (2) the pathophysiologic mechanism for the development of both ulcers and strictures may involve a direct action of diclofenac within these lesions; (3) colonoscopy may be superior to barium studies in evaluating patients receiving diclofenac who have iron deficiency anemia and/or Hemoccult-positive stools. PMID- 1444696 TI - Refractory potassium repletion due to magnesium deficiency. PMID- 1444697 TI - The effect of smoking on elderly drivers. PMID- 1444698 TI - Significance of drug interactions with rifampin in Pneumocystis carinii pneumonia prophylaxis. PMID- 1444699 TI - Toxicology as a discipline of internal medicine: the time has come. PMID- 1444700 TI - [Recent advancement in surgical treatment for esophageal cancer]. PMID- 1444701 TI - Improved survival in mice with diet-induced pancreatitis treated with new potent protease inhibitor, E-3123 and a broad spectrum antibiotic, cefmetazole. AB - This study was designed to evaluate the infectious factor in the pathogenesis of acute pancreatitis and the effects of a combination therapy with a new potent protease inhibitor, E-3123, and a broad spectrum antibiotic cefmetazole (CMZ) in mice with CDE diet-induced severe acute pancreatitis. Combination therapy with E 3123 and CMZ showed significant protective effects against the high mortality rate, increased serum amylase and ascitic fluid amylase levels, pancreatic amylase and lysosomal enzyme content, plasma endotoxin levels, redistribution of lysosomal enzyme from the lysosomal to the zymogen fraction, lysosomal and mitochondrial fragility, and also improved the histological findings when compared with the E-3123 alone. These results suggest that infections factors play an important role in the development of severe acute pancreatitis and that protease inhibitors in combination with antibiotics may be clinically beneficial. PMID- 1444702 TI - Protective effects of combined therapy with a protease inhibitor, ONO 3307, and a xanthine oxidase inhibitor, allopurinol on temporary ischaemic model of pancreatitis in rats. AB - The protective effect of a new potent protease inhibitor, ONO 3307, in combination with a xanthine oxidase inhibitor, allopurinol, was tested in pancreatico-biliary duct obstruction (PBDO) with temporary pancreatic ischemia in rats. After PBDO with ischemia, we observed hyperamylasemia, pancreatic edema, congestion of amylase and lysosomal enzyme cathepsin B as well as impaired output of amylase and cathepsin B into the pancreatic juice and a redistribution of lysosomal enzyme from the lysosomal fraction to the zymogen fraction. The administration of ONO 3307 plus allopurinol almost completely prevented the pancreatic injuries induced by PBDO with ischemia. These results indicate the important roles of temporary pancreatic ischemia in the pathogenesis of pancreatic damage and the usefulness of combination therapy with a new potent protease inhibitor and xanthine oxidase inhibitor in the protection against clinical acute pancreatitis. PMID- 1444703 TI - [Protective effect of prostaglandin E2 on cerulein-induced rat pancreatitis]. AB - In order to clarify the effect of prostaglandin E2 (PGE2) on cerulein-induced rat pancreatitis, we investigated the interaction of PGE2 with cerulein or secretin. Intravenous infusion of 10 micrograms/kg.h cerulein inhibited external secretion of the pancreas from one hour and caused macroscopic edema at 3 hours. Administration of PGE2 relieved the inhibitory effect of supramaximal dose of cerulein and decreased the pancreatic edema. The 100 micrograms/kg.hr PGE2 had no significant effect on the pancreatic juice volume and amylase secretion stimulated with 0.2 micrograms/kg.hr of cerulein. Intravenous injection of 100 micrograms/kg PGE2 inhibited both the volume and amylase secretion of pancreatic juice stimulated with 1 U/kg.h of secretin. The protective effect of PGE2 on cerulein-induced pancreatitis was not the stimulation on secretion but caused the cytoprotective effect of PG such as stabilization of cytoplasmic and lysosomal membrane. PMID- 1444704 TI - [Cystic falx meningioma: report of a case with difficulty in radiologic diagnosis]. AB - A case of cystic falx meningioma in the frontal region in which preoperative neuroradiologic diagnosis was difficult is reported. This 33-year-old man had suffered from epileptic seizures three times in one month. Physical and neurological examinations on admission were normal. A cystic mass with a small nodule was found on CT in the frontal region. Thin wall was enhanced smoothly and the nodule attached to the falx was enhanced heterogeneously. The mass was considered to be an extra-axial lesion on MRI. The right anterior falcine artery seemed to feed the mass. Bifrontal craniotomy was performed. Cyst was evacuated, and a soft reddish mass was subtotally removed. Cyst fluid was yellowish and protein content was 3.5 g/dl. Histopathological diagnosis was a meningotheliomatous meningioma and tumor cells were present also in the thin cyst wall. At the second operation the mass was completely removed, cyst wall inclusive. When we encounter a cystic mass in the sites of predilection of meningiomas, we have to consider the possibility of a cystic meningioma. If the mass has meningeal vascularization, a correct diagnosis is not difficult. Taking the location of the mass into consideration, an accurate interpretation of CT and MRI findings indicating extra-axial nature of the mass is indispensable. PMID- 1444705 TI - [Possibilities for using bedside cards as secondary comparison in trace element studies with the PCR technique]. AB - When fresh blood is not available as a control in stain investigations extracted teeth, hair, preserved tissue samples, histological slides, cigarette butts or used stamps can also be used. This paper reports on a stain investigation performed 7 months after the death of the victim, where a bedside card from the medical records was successfully employed as a control blood sample. In a series of 10 bedside cards up to 9 years old, the investigation with the PCR method showed recognizable patterns in the STR systems SE 33 and TC 11. Matching patterns could be found from the 4 sections of each card (anti A, anti B, anti AB and anti D). A comparison of the oldest card with a fresh blood sample of the patient also showed matching patterns. AMPFLPs were successful with more recent cards. Using the PCR method typing of bedside cards from medical records up to 10 years old can be used in stain investigations. PMID- 1444706 TI - [Modern image documentation in forensic medicine]. PMID- 1444707 TI - [Frankfurt am Main--the German capital of crime?]. PMID- 1444708 TI - [Morphologic patterns in suicidal stab injuries of the neck]. AB - Stabs into the neck are seen very seldom in connection with suicide. If there are features typical of suicide, the medico-legal analysis of the pathomorphological findings essentially may contribute to the differentiation from homicidal injuries. On the basis of the observations already published and three own cases an attempt is made to derive criteria of self-infliction for differential diagnosis from the autopsy findings. Concomitant injuries and combination with another method of suicide have turned out to be important indications of self infliction. PMID- 1444709 TI - [Suicide with chloroquine combined with maprotiline and trimipramine]. AB - Report on suicide with chloroquine in combination with maprotiline and trimipramine. Chloroquine and his metabolite monodesethylchloroquine could be determined in organs and body fluids. The highest organ-concentrations of chloroquine were found in liver and kidney. The survival time and dose are discussed. PMID- 1444710 TI - [Gunshot injury caused by a training bullet]. AB - In the course of a scuffle a 50-year old man has been shot by a revolver. The culprit and witnesses state, there has been only one shot, whereas the victim declared having been shot twice. The medico-legal investigation revealed a gunshot wound that passed through the left thigh, a grazing shot of the right hand and a superficial lesion of the skin at the forehead with sprinkled gunshot residue in the epidermis. The investigation confirmed the statement of the victim: the first shot to the forehead was caused by a plastic training cartridge, the second to the right hand and thigh by a cartridge loaded with an ordinary bullet. PMID- 1444711 TI - [Aspiration of gastric contents in hanging with typical position of the strangulation cord and free suspension]. AB - Among 193 cases of hanging from the years 1978 to 1991 examined in the institute of Forensic Medicine of the Freie Universitat Berlin 8 cases with an aspiration of stomach contents had been reported. Herefrom 3 cases were hanging in a "typical" position (suspension point at the back of the head, free suspension of the hanging body) and did not undergo resuscitation. By free suspension of the hanging body the observed massive aspiration of gastric contents only can be explained by an at least partly open connecting passage between the laryngeal entry and the entrance of the oesophagus. The post mortem flowing in of stomach contents as well as a post mortem gastro-oesophageal peristalsis seem not to be able for explicating the findings. Differences in important parameters (e.g. gastric contents, alcoholization) to the cases of hanging without aspiration were not found. Even by free suspension of the body, running noose and point of suspension in the back of the neck sometimes the connection between larynx and oesophagus may stay open, especially when by emesis a high pressure is produced by the stomach. PMID- 1444712 TI - Emodin O-methyltransferase from Aspergillus terreus. AB - Emodin O-methyltransferase, an enzyme catalyzing methylation of the 8-hydroxy group of emodin, was identified in the mould Aspergillus terreus IMI 16043, a (+) geodin producing strain. The enzyme catalyzed the formation of questin from emodin and S-adenosyl-L-methionine. By chromatography on DEAE-cellulose, Phenyl Sepharose, Q-Sepharose, Hydroxyapatite, and CM-cellulose, emodin O methyltransferase was purified to apparent homogeneity. The purified protein had a molecular weight of 322 kDa as estimated by gel filtration and 53.6 kDa as estimated by gel electrophoresis under denaturing conditions, suggesting that the active enzyme was a homohexamer. The enzyme showed pI 4.4 and optimum pH 7-8. Magnesium ion or manganese ion was not an absolute requirement, nor increased the enzyme activity. The enzyme had strict substrate specificity and very low Km values for both emodin (3.4 x 10(-7) M) and S-adenosyl-L-methionine (4.1 x 10(-6) M). PMID- 1444713 TI - A strictly anaerobic nitrate-reducing bacterium growing with resorcinol and other aromatic compounds. AB - With resorcinol as sole source of energy and organic carbon, two stains of gram negative, nitrate-reducing bacteria were isolated under strictly anaerobic conditions. Strain LuBRes1 was facultatively anaerobic and catalase- and superoxide dismutase-positive. This strain was affiliated with Alcaligenes denitrificans on the basis of substrate utilization spectrum and peritrichous flagellation. Strain LuFRes1 could grow only under anaerobic conditions with oxidized nitrogen compounds as electron acceptor. Cells were catalase-negative but superoxide dismutase-positive. Since this strain was apparently an obligate nitrate reducer, it could not be grouped with any existing genus. Resorcinol was completely oxidized to CO2 by both strains. Neither an enzyme activity reducing or hydrolyzing the resorcinol molecule, nor an acyl-CoA-synthetase activating resorcylic acids or benzoate was detected in cell-free extracts of cells grown with resorcinol. In dense cell suspensions, both strains produced a compound which was identified as 5-oxo-2-hexenoic acid by mass spectrometric analysis. This would indicate a direct, hydrolytic cleavage of the resorcinol nucleus without initial reduction. PMID- 1444714 TI - Light and the recovery from heat shock induce the synthesis of 38 kDa mitochondrial proteins in Neurospora crassa. AB - The effect of light on the protein synthesis pattern in the mitochondria of Neurospora crassa was examined by in vivo labelling with [35S]-methionine and two dimensional gel electrophoresis. A brief 5-min illumination induced the rapid and transient synthesis of a 38-kDa protein. White collar-mutants were not stimulated to synthesize this protein by light. A protein of a similar molecular weight and isoelectrical point was synthesized during recovery from heat shock. PMID- 1444715 TI - The effect of pH on the heat production and membrane resistance of Streptococcus bovis. AB - Non-growing cultures of Streptococcus bovis JB1 which were incubated in 2-[N moropholino] ethane-sulfonic acid (MES)-phosphate buffer (pH 6.8) and glucose (2 g/l) produced heat at a rate of 0.17 mW/mg protein, and this rate was proportional to the enthalpy change of the homolactic fermentation. Since the growth-independent heat production could be eliminated by dicyclohexylcarbodiimide (DCCD), an inhibitor of F1F0 ATPases, it appeared that virtually all of the energy was being used to counteract proton flux through the cell membrane. When the pH was decreased from 6.8 to 5.8, heat production and glucose consumption increased, the electrical potential (delta psi) declined, the chemical gradient of protons (Z delta pH) increased, and there was a small increase in total protonmotive force (delta p). Further decreases in pH (5.8 to 4.5) caused a marked decrease in heat production and glucose consumption even though there was only a small decline in membrane voltage. Based on the enthalpy of ATP (4 kcal or 16.8 kJ/mol), it appeared that 38% of the wattage was passing through the cell membrane. The relationship between membrane voltage and membrane wattage or glucose consumption was non-linear (non-ohmic), and it appeared that the resistance of the membrane to current flow was not constant. Based on the electrical formula, resistance = voltage2/wattage and resistance = voltage/amperage, there was a marked increase in membrane resistance when the pH was less than 6.0. The increase in membrane resistance at low pH allowed S. bovis to maintain its membrane potential and expend less energy when its ability to ferment glucose was impaired. PMID- 1444716 TI - An Escherichia coli mutant containing only demethylmenaquinone, but no menaquinone: effects on fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate respiration. AB - The mutant strain AN70 (ubiE) of Escherichia coli which is known to lack ubiquinone (Young IG et al. 1971), was analyzed for menaquinone (MK) and demethylmenaquinone (DMK) contents. In contrast to the wild-type, strain AN70 contained only DMK, but no MK. The mutant strain was able to grow with fumarate, trimethylamine N-oxide (TMAO) and dimethylsulfoxide (DMSO), but not with nitrate as electron acceptor. The membranes catalyzed anaerobic respiration with fumarate and TMAO at 69 and 74% of wild-type rates. DMSO respiration was reduced to 38% of wild-type activities and nitrate respiration was missing (less than or equal to 8% of wild-type), although the respective enzymes were present in wild-type rates. The results complement earlier findings which demonstrated a role for DMK only in TMAO respiration (Wissenbach et al. 1990). It is concluded, that DMK (in addition to MK) can serve as a redox mediator in fumarate, TMAO and to some extent in DMSO respiration, but not in nitrate respiration. In strain AN70 (ubiE) the lack of ubiquinone (Q) is due to a defect in a specific methylation step of Q biosynthesis. Synthesis of MK from DMK appears to depend on the same gene (ubiE). PMID- 1444717 TI - Isopropylbenzene (cumene)--a new substrate for the isolation of trichloroethene degrading bacteria. AB - Various bacterial isolates from enrichments with isopropylbenzene (cumene), toluene or phenol as carbon and energy sources were tested as to their potential to oxidize trichloroethene (TCE). In contrast to toluene and phenol, all isolates enriched on isopropylbenzene were able to oxidize TCE. Two isolates, strain JR1 and strain BD1, were identified as Pseudomonas spec. and as Rhodococcus erythropolis, respectively. TCE oxidation was accompanied by the liberation of stoichiometric amounts of chloride. Initial TCE oxidation rate increased proportional to the substrate concentration from 25 to 200 microM TCE. Maximal initial TCE-degradation rates found here were 4 to 5 nmol.min-1.mg protein-1. The TCE degradation rate decreased with time. The two isolates showed a temperature optimum for TCE degradation between 10 and 20 degrees C. In addition to TCE, R. erythropolis BD1 degraded only cis- and trans-dichloroethene whereas Pseudomonas spec. JR1 was able to oxidize also 1,1-dichloroethene, vinyl chloride, trichloroethane, and 1,2-dichloroethane. PMID- 1444718 TI - N5-methyltetrahydromethanopterin: coenzyme M methyltransferase in methanogenic archaebacteria is a membrane protein. AB - An assay is described that allows the direct measurement of the enzyme activity catalyzing the transfer of the methyl group from N5-methyltetrahydromethanopterin (CH3-H4MPT) to coenzyme M (H-S-CoM) in methanogenic archaebacteria. With this method the topology, the partial purification, and the catalytic properties of the methyltransferase in methanol- and acetate-grown Methanosarcina barkeri and in H2/CO(2)-grown Methanobacterium thermoautotrophicum were studied. The enzyme activity was found to be associated almost completely with the membrane fraction and to require detergents for solubilization. The transferase activity in methanol-grown M. barkeri was studied in detail. The membrane fraction exhibited a specific activity of CH3-S-CoM formation from CH3-H4MPT (apparent Km = 50 microM) and H-S-CoM (apparent Km = 250 microM) of approximately 0.6 mumol.min 1.mg protein-1. For activity the presence of Ti(III) citrate (apparent Km = 15 microM) and of ATP (apparent Km = 30 microM) were required in catalytic amounts. Ti(III) could be substituted by reduced ferredoxin. ATP could not be substituted by AMP, CTP, GTP, S-adenosylmethionine, or by ATP analogues. The membrane fraction was methylated by CH3-H4MPT in the absence of H-S-CoM. This methylation was dependent on Ti(III) and ATP. The methylated membrane fraction catalyzed the methyltransfer from CH3-H4MPT to H-S-CoM in the absence of ATP and Ti(III). Demethylation in the presence of H-S-CoM also did not require Ti(III) or ATP. Based on these findings a mechanism for the methyltransfer reaction and for the activation of the enzyme is proposed. PMID- 1444719 TI - Genes for a second terminal oxidase in Bradyrhizobium japonicum. AB - Bradyrhizobium japonicum possesses a mitochondria-like respiratory chain terminating with an aa3-type cytochrome c oxidase. The gene for subunit I of this enzyme (coxA) had been identified and cloned previously via heterologous hybridization using a Paracoccus denitrificans DNA probe. In the course of these studies, another B. japonicum DNA region was discovered which apparently encoded a second terminal oxidase that was different from cytochrome aa3 but also belonged to the superfamily of heme/copper oxidases. Nucleotide sequence analysis revealed a cluster of at least four genes, coxMNOP, organized most probably in an operon. The predicted coxM gene product shared significant similarity with subunit II of cytochrome c oxidases from other organisms: in particular, all of the proposed CuA ligands were conserved as well as three of the four acidic amino acid residues that might be involved in the binding of cytochrome c. The coxN gene encoded a polypeptide with about 40% sequence identity with subunit I representatives including the previously found CoxA protein: the six presumed histidine ligands of the prosthetic groups (two hemes and CuB) were strictly conserved. A remarkable feature of the DNA sequence was the presence of two genes, coxO and coxP, whose products were both homologous to subunit III proteins. A B. japonicum coxN mutant strain was created by marker exchange mutagenesis which, however, exhibited no obvious defects in free-living, aerobic growth or in root nodule symbiosis with soybean. This shows that the coxMNOP genes are not essential for respiration in the N2 fixing bacteroid. PMID- 1444720 TI - Purification and characterization of a methanol-induced cobamide-containing protein from Sporomusa ovata. AB - The major cobamide-containing protein from methanol-utilizing Sporomusa ovata was 8-fold enriched to apparent homogeneity. The protein exhibited a molecular mass of 40 kDa and of 38 kDa determined by gel filtration and by SDS-polyacrylamide gel electrophoresis, respectively. This finding indicates a monomeric protein structure. Monospecific polyclonal antisera raised against the protein did not cross react with another cobamide-containing protein from Sporomusa cells. Only the 40 kDa cobamide-containing protein was induced by methanol, since proteins from cells grown on 3,4-dimethoxybenzoate, betaine H2/CO2, or fructose showed faint or no cross reaction. Hence, the 40 kDa cobamide-containing protein is presumably involved in the methyl-transfer reaction of the methanol metabolism. The purified enzyme revealed 1.1 mol of p-cresolyl cobamide per mol of protein, but it lacked of iron-sulfur centers. Remarkably, the cofactor was firmly bound to its protein. PMID- 1444721 TI - Neuroendocrine response to L-5-hydroxytryptophan challenge in prepubertal major depression. Depressed vs normal children. AB - The neuroendocrine response to L-5-hydroxytryptophan was compared in 37 prepubertal children who met the Research Diagnostic Criteria for major depressive disorder with that in 23 normal children with no lifetime history of any psychiatric disorder and very low rates of depression in both first- and second-degree relatives. Intravenous L-5-hydroxytryptophan (0.8 mg/kg) was given over a 1-hour interval after preloading with oral carbidopa, an inhibitor of peripheral but not central L-5-hydroxytryptophan metabolism. L-5 Hydroxytryptophan, a precursor of serotonin, increases serotonin turnover in the central nervous system when given after carbidopa. Seven (19%) of the 37 children with major depressive disorder and two (9%) of the 23 normal children had nausea or vomiting and therefore did not complete the full infusion. They were subsequently excluded from data analysis. After this stimulation, prolactin, cortisol, and growth hormone secretion were compared between diagnostic groups. The depressed children secreted significantly less cortisol (effect size, 0.70) and significantly more prolactin (effect size, 0.83). There was a sex-by diagnosis interaction in prolactin response to L-5-hydroxytryptophan and, on examination, the prolactin hypersecretion was seen in depressed girls but not in depressed boys compared with same-sex controls. There was no significant stimulation of growth hormone in either group. These findings are consistent with dysregulation of central serotonergic systems in childhood major depression. PMID- 1444722 TI - Neuroendocrine responses to m-chlorophenylpiperazine and L-tryptophan in bulimia. AB - Preclinical and clinical evidence supports a theory of serotonin (5 hydroxytryptamine [5-HT]) dysregulation in bulimia. We therefore studied the prolactin (PRL) and cortisol responses following challenges with the postsynaptic 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg orally, the 5 HT precursor L-tryptophan, 100 mg/kg intravenously, and placebo in a group of 28 normal weight bulimic patients and 16 healthy controls. Patients with bulimia, regardless of the presence of major depression, had significantly blunted PRL responses following m-CPP administration compared with those in controls. In contrast, only bulimic patients with concurrent major depression had significantly blunted PRL responses following L-tryptophan administration compared with those in nondepressed bulimic patients and controls. Cortisol responses following m-CPP were not significantly different for bulimic patients vs controls, although there was a trend toward blunted cortisol responses following L-tryptophan administration in the depressed bulimic patients. These differences in neuroendocrine responses were not related to differences in age, percent of average body weight, medications, time of day, peak plasma drug levels, or baseline estradiol levels. Seasonal variations in PRL responses to both agents were identified, although covariation for season did not alter the group differences. The PRL responses following m-CPP administration were inversely correlated to baseline cortisol levels in the bulimic patients, but not in the controls, suggesting a dampening effect by hypothalamic-pituitary-adrenal axis dysfunction on postsynaptic 5-HT receptor sensitivity. The reasons for the differing hormonal responses to these two serotonergic agents may relate to differential involvement of presynaptic and postsynaptic mechanisms, 5-HT receptor subtypes, and anatomical loci of action. The blunted PRL responses to m CPP administration suggest that postsynaptic 5-HT receptor sensitivity is altered in bulimia nervosa, and that similar alterations in 5-HT receptors at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms. PMID- 1444723 TI - Effect of axis II diagnoses on treatment outcome with clomipramine in 55 patients with obsessive-compulsive disorder. AB - We used the Structured Interview for DSM-III Personality Disorders to diagnose DSM-III personality disorders systematically in 55 patients with obsessive compulsive disorder in the active-treatment cell of a controlled trial of clomipramine hydrochloride. Patients with a cluster A personality disorder had significantly higher obsessive-compulsive disorder severity scores at baseline, and the number of personality disorders was strongly related to baseline severity of obsessive-compulsive disorder symptoms. At the conclusion of the 12-week study, we found no significant difference in treatment outcome with clomipramine between those patients with at least one personality disorder and those with no personality disorders. However, the presence of schizotypal, borderline, and avoidant personality disorders, along with total number of personality disorders, did predict poorer treatment outcome. These variables were strongly related to having at least one cluster A personality disorder diagnosis, which was also a strong predictor of poorer outcome. Implications of these findings are discussed. PMID- 1444724 TI - Anxiogenic effects of caffeine in patients with anxiety disorders. AB - The effects on measures of anxiety from two doses of oral caffeine (250 and 500 mg) and placebo were compared in 12 patients with generalized anxiety disorder (GAD), 12 patients with panic disorder, and 12 normal subjects. Caffeine produced significantly less decrease in electroencephalographic alpha wave activity, greater decrease in N1-P2 auditory evoked potential amplitude, and greater increased in skin conductance level, systolic and diastolic blood pressure, critical fusion flicker frequency, and self-ratings of anxiety and sweating in patients with GAD than in normal patients. Patients with panic disorder showed different reactivity than normal patients did with respect to electroencephalographic alpha waves, N2 latency, N2-P2 auditory evoked potential amplitude, and physical tiredness but were less reactive than patients with GAD on several variables. It is concluded that patients with GAD are abnormally sensitive to caffeine and that the data support the view that panic disorder is a separable disorder from GAD. PMID- 1444725 TI - Physiologic responses to loud tones in Israeli patients with posttraumatic stress disorder. AB - Orbicularis oculi (eye blink) electromyogram, skin conductance, and heart rate responses to 15 consecutive 95-dB, 500-millisecond, 1000-Hz tones with 0 millisecond rise and fall times were measured in 14 patients with posttraumatic stress disorder, 14 patients with other anxiety disorders, 15 mentally healthy subjects with past traumatic experiences, and 19 mentally healthy subjects with no trauma history. The patients with posttraumatic stress disorder showed significantly larger skin conductance and heart rate responses and a trend toward larger electromyogram responses to the tones than every other group. These effects were not explained by subjective anxiety, resting physiologic arousal, physiologic arousal preceding the tone trials, or initial physiologic responsivity. The group with posttraumatic stress disorder was the only one that failed to show habituation of skin conductance responses. PMID- 1444726 TI - Naltrexone and coping skills therapy for alcohol dependence. A controlled study. AB - Ninety-seven alcohol-dependent patients were treated for 12 weeks in a double blind, placebo-controlled study evaluating naltrexone and two manual guided psychotherapies in the treatment of alcohol dependence. Patients were randomized to receive either naltrexone or placebo and either coping skills/relapse prevention therapy or a supportive therapy designed to support the patient's own efforts at abstinence without teaching specific coping skills. Naltrexone proved superior to placebo in measures of drinking and alcohol-related problems, including abstention rates, number of drinking days, relapse, and severity of alcohol-related problems. Medication interacted with the type of psychotherapy received. The cumulative rate of abstinence was highest for patients treated with naltrexone and supportive therapy. For those patients who initiated drinking, however, patients who received naltrexone and coping skills therapy were the least likely to relapse. PMID- 1444727 TI - Desipramine treatment of cocaine dependence in methadone-maintained patients. AB - We performed a double-blind, placebo-controlled, randomized 12-week trial of desipramine hydrochloride treatment of cocaine dependence among methadone maintained patients. Fifty-nine patients completed the 12-week medication trial (36 received desipramine and 23 received placebo), and 94% were recontacted 1, 3, and 6 months after treatment. There were significantly more dropouts in the desipramine than in the placebo group. Baseline to 12-week comparisons of Addiction Severity Index interview data indicated that both groups showed improvements. At 12 weeks, the desipramine group showed significantly better psychiatric status than the placebo group but did not differ from the placebo group on any of 21 other outcome measures, including cocaine use. During the 12 week medication phase and at the 1-month follow-up evaluation, urine toxicology screenings showed no significant difference between groups, but the placebo group had significantly less cocaine use at both the 3- and 6-month follow-up points. We conclude that desipramine has few benefits with regard to control of cocaine use in this population. PMID- 1444728 TI - Pharmacotherapy for cocaine-abusing methadone-maintained patients using amantadine or desipramine. AB - In a double-blind, placebo-controlled 12-week randomized clinical trial, we compared amantadine hydrochloride (300 mg/d; n = 33), desipramine hydrochloride (150 mg/d; n = 30), and placebo (n = 31) in the treatment of cocaine-abusing methadone-maintained patients. Treatment retention and medication compliance were excellent, with more than 75% of the patients completing the full 12-week trial. Although reported cocaine abuse was significantly lower in the medicated groups compared with the placebo group at week 4, this difference became nonsignificant at week 8, and no difference was found in cocaine-free urine samples. Future studies of amantadine and desipramine treatment in these patients should consider alternatives to methadone hydrochloride, such as buprenorphine hydrochloride, and the selection of more homogeneous patient subgroups, such as depressed cocaine abusers. PMID- 1444729 TI - New pharmacotherapies for cocaine dependence ... revisited. PMID- 1444730 TI - Drugs for cocaine dependence: not easy. PMID- 1444731 TI - Geographic variations in the prevalence of schizophrenia. PMID- 1444732 TI - Autofluorescent Charcot-Leyden crystals. PMID- 1444733 TI - Paneth cell-like change of the prostate. PMID- 1444734 TI - HMB-45 staining in pigmented pheochromocytoma. PMID- 1444735 TI - The time is now. Checklists for surgical pathology reports. PMID- 1444736 TI - New safety considerations for the acquired immunodeficiency syndrome autopsy. PMID- 1444737 TI - Autopsies and attitudes. Where do we go from here? PMID- 1444738 TI - Interinstitutional assessment of colorectal carcinoma surgical pathology report adequacy. A College of American Pathologists Q-Probes study of practice patterns from 532 laboratories and 15,940 reports. AB - In 1991, the College of American Pathologist's Q-Probes Quality Improvement Program evaluated practices in 532 institutions for pathologic information provided in surgical pathology reports of 15,940 resected primary colorectal carcinomas. Participating institutions studied their last 30 completed cases and were from the United States (98%), Canada (1.5%), and Australia (0.4%). The influence of various institutional differences and other practice patterns were analyzed to determine factors associated with an increased institutional likelihood of providing information on pathology reports. The one practice significantly associated with increased likelihood of providing complete oncologic pathology information on eight of 11 gross and microscopic information items surveyed was the use of a standard report form or checklist. Other institutional differences bearing inconsistent associations included teaching institution status, presence of pathology residency, use of microscopic descriptions, institution bedsize category, and performance of DNA ploidy analysis. The development and adoption of a standardized report form or checklist for each case is a simple but effective means to assure report adequacy and consistent communication of oncologic pathology information. In conjunction with accompanying criteria for its accurate use, this process can be considered a practice guideline or practice parameter that can be extended to the surgical pathology examination of all resected malignant neoplasms. PMID- 1444739 TI - Confidentiality of human immunodeficiency virus status on autopsy reports. Council on Ethical and Judicial Affairs, American Medical Association. AB - The medical profession has long recognized the need to maintain the confidentiality of a patient's medical condition, particularly when stigmatizing conditions, like human immunodeficiency virus infections, are involved. The obligation to maintain confidentiality continues after the death of the patient. At the same time, there may be public health concerns that justify limited disclosure of a deceased person's human immunodeficiency virus status. This report provides guidelines that balance the need for confidentiality with public health concerns when a deceased person infected with the human immunodeficiency virus undergoes an autopsy. PMID- 1444740 TI - Postmortem recovery of human immunodeficiency virus type 1 from plasma and mononuclear cells. Implications for occupational exposure. AB - OBJECTIVE: To determine the ability to recover human immunodeficiency virus type 1 (HIV-1) from the plasma and mononuclear cell (MNC) fractions of postmortem blood samples from patients with the acquired immunodeficiency syndrome. DESIGN: Blood was randomly cultured post mortem from 41 patients with the acquired immunodeficiency syndrome. Plasma and MNC cultures were performed as well as serum antigen assays. Evaluation parameters included MNC recovery, MNC viability, time of sample collection after death, time of inoculation of coculture following sample acquisition, and storage conditions of the body (ie, refrigeration vs nonrefrigeration). SETTING: Blood samples were obtained from patients with the acquired immunodeficiency syndrome being prepared for burial at metropolitan area funeral homes. PATIENTS: Postmortem samples were obtained from 41 patients with the acquired immunodeficiency syndrome. MAIN OUTCOME MEASURE: Virus recovery from either cells or plasma. RESULTS: Human immunodeficiency virus type 1 was recovered from 21 (51%) of 41 patients at 0.5 to 21.25 hours postmortem. Recovery of HIV-1 from plasma and/or MNC fractions was variable with 6 (15%) of 41 plasma+/MNC+, 12 (29%) of 41 plasma-/MNC+, three (7%) of 41 plasma+/MNC-, and 20 (49%) of 41 plasma-/MNC-. Plasma p24 levels (> 30 pg/mL) were detectable in 14 (48%) of 37 samples tested. Of those culture-positive patients, seven (33%) of 21 were refrigerated compared with the culture-negative group in which 10 (50%) of 20 were refrigerated. Time from death until specimen acquisition was the only factor significantly associated with recovery of HIV-1. CONCLUSION: These results should be useful for health care workers and others exposed to postmortem blood from HIV-infected individuals and should lead to changes in the processing practices of morticians and/or pathologists for HIV-1-infected cadavers. PMID- 1444741 TI - A decade of acceptable autopsy rates. Does concordance of clinician and pathologist views explain relative success? AB - In an attempt to better understand the basis and significance of an annual autopsy rate consistently over 45% for the past decade, we recently investigated the attitudes and practices of 36 pathologists and 176 clinicians in our institution with respect to the function of the autopsy service and the utility of the autopsy. The autopsy report was "not used in a consistent manner" by 57% of clinical respondents. Several clinicians thought that autopsy reports were too long (20%) and too slow (38%), but not with the frequency that pathologists did, 73% and 58%, respectively. Significantly more pathologists than clinicians believed autopsy rates have fallen over the past 20 years because (1) people think that everything about the deceased is already known, (2) medical students are poorly educated about the autopsy, (3) pathologists have diminished interest, (4) physicians fear litigation, (5) physicians fear "being wrong," (6) pathologists lack financial incentives, and (7) Joint Commission on Accreditation of Healthcare Organizations requirement is not in place. Perceptions regarding the frequency of major discrepancies between clinical and autopsy findings were comparable, 17% and 13%, for pathologists and clinicians, respectively. Our "high" institutional autopsy rate does not reflect concordance of perceptions expressed by clinicians and pathologists and, thus, other factors may be important in the maintenance of an acceptable rate. PMID- 1444742 TI - Autopsy-determined causes of death following cardiac transplantation. A study of 81 patients and literature review. AB - The principal and contributory causes of death in 81 autopsied heart transplant patients who died at Groote Schuur Hospital, Cape Town, South Africa, were investigated and subdivided according to the immunosuppressive regimen used as well as the postoperative survival period. Mean graft survival was 488 days. Chronic rejection (30%), infection (23%), and acute rejection (20%) were the most common principal causes of death. Both fatal and nonfatal infections involved the lung predominantly. A review of the literature revealed 198 other autopsied heart transplant patients whose principal cause of death could be analyzed; infection accounted for almost half of these latter deaths, followed by acute and chronic rejection. Contributory causes of death in the 81 patients were as follows: infection (17%), acute rejection (16%), chronic rejection (14%), miscellaneous conditions (14%), embolism (14%), pancreatitis (11%), peptic ulcer (9%), inadequate donor heart (3%), and malignancy (1%). We conclude that infection, together with acute and/or chronic rejection, are still the major causes of death in heart transplant patients. PMID- 1444743 TI - Attitudes of funeral directors and embalmers toward autopsy. AB - Although physician and family attitudes toward autopsy have been suggested as factors leading to declining autopsy rates, attitudes of funeral directors and embalmers toward autopsy have not been studied. We surveyed members of the Illinois Funeral Directors Association concerning beliefs about the purposes of autopsy, problems they experienced with autopsied cases, and the advice they gave to family members about permitting autopsy. Three hundred eight (42.2%) of 730 funeral directors and embalmers responded to the questionnaire. Although 80.3% believed that autopsy served a purpose, 46.4% had counseled families not to permit autopsy, and 16.6% did so more than half the time. Perceived difficulty in embalming autopsied cases (odds ratio, 2.3), family concern about the risk of disfigurement (odds ratio, 1.9 to 2.2), having attempted to talk to a pathologist or hospital administrator about a poorly performed autopsy (odds ratio, 2.0), and belief in the purpose of autopsy (odds ratio, 0.38), were significant independent predictors of counseling against autopsy. Of funeral directors who counseled against autopsy, 28.3% reported that families never permitted autopsy, and 39.4% reported that families only occasionally permitted autopsy, in cases where they had counseled against it. Funeral directors from Illinois counties with 1989 medical certificate case autopsy rates of less than 5% counseled against autopsy more frequently than funeral directors from counties with higher autopsy rates. We conclude that although most funeral directors and embalmers believe in the purposes of the autopsy, difficulties in embalming autopsied cases, and family concern about the risk of disfigurement, may lead members of the funeral profession to counsel against autopsy, and that such advice may influence families not to permit an autopsy. PMID- 1444744 TI - Accumulation of brown adipose tissue and nutritional status. A prospective study of 366 consecutive autopsies. AB - Increased amounts of brown adipose tissue have been reported to occur in association with several diseases. The objective of the present study was to determine whether brown adipose tissue accumulation is related to nutritional status. Histologic sections of periadrenal tissue prospectively obtained at consecutive autopsies from 366 adults were examined. The cases were separated into three groups: malnourished (101 autopsies), normotrophic (128 autopsies), and obese (137 autopsies), according to the Quetelet index. Of these patients, 89 had brown adipose tissue accumulation, 35 were malnourished, 32 were normotrophic, and 22 were obese. The results showed a correlation between brown adipose tissue and patient nutritional status and a higher brown adipose tissue accumulation in malnourished patients. Cardiovascular disease was the most common type of illness present in the cases with brown adipose tissue accumulation. PMID- 1444745 TI - The Bethesda System. A proposal for reporting abnormal cervical smears based on the reproducibility of cytopathologic diagnoses. AB - In the Bethesda System, noninvasive squamous abnormalities are classified as atypical squamous cells of undetermined significance (ASQUS), low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions. The Bethesda System eliminates two diagnostic distinctions that are made in the dysplasia/carcinoma in situ and cervical intraepithelial neoplasia (CIN) classifications, CIN1 vs koilocytotic atypia and CIN2 vs CIN3, and maintains three others, negative vs ASQUS, ASQUS vs koilocytotic atypia, and CIN1 vs CIN2. To determine whether the diagnostic distinctions preserved in the Bethesda System are made more consistently than those eliminated, we analyzed the interobserver reproducibility of two cytopathologists in classifying 257 smears. The findings indicate that the distinctions retained in the Bethesda System are more reproducible than those eliminated. Specifically, cases classified as koilocytotic atypia were distinguished from CIN1 no more reproducibly than predicted by chance, whereas CIN2 and CIN3 were distinguished as consistently as any other pair of diagnoses examined. In 13 cases in which there was interobserver discordance, one reviewer classified the smear as ASQUS and the other reviewer diagnosed CIN2 or CIN3. The findings in this study suggest that smears showing koilocytotic atypia and/or CIN1 may be reported as low-grade squamous intraepithelial lesions without further specification. In contrast, smears showing high-grade squamous intraepithelial lesions may be further classified as CIN2 or CIN3 in accordance with the Bethesda guidelines. Since the diagnosis of ASQUS is applied to smears showing a wide spectrum of changes, management of patients with the diagnosis of ASQUS will be facilitated by providing an explanatory note and/or recommendations when appropriate. PMID- 1444746 TI - The effectiveness of cytologic evaluation of products of conception. AB - In therapeutic abortions, the major issue of concern to physicians and patients is the documentation of an intrauterine pregnancy and its successful termination. We describe an inexpensive cytologic approach by which results can be obtained in a few hours and a permanent method of documentation provided. Three hundred cases of therapeutic abortion were evaluated by the cytologic method, and 93.7% of cases were positive, ie, they demonstrated the presence of nucleated red blood cells and/or placental villi. By routine histologic examination, 96.3% of the cases were positive. In only 2% of cases was the cytologic finding negative and the histologic finding positive. If the histologic finding is also negative, we recommend, based on our data, that the patient be reevaluated. PMID- 1444747 TI - Sudden death associated with aortitis and fibrosclerosing disease of the conduction system. AB - Aortitis is known to complicate a number of autoimmune diseases and syphilis. In most patients with autoimmune disease, arthritis is the initial presentation followed by aortic insufficiency. We report two cases of ostensibly healthy, middle-aged men in whom the initial manifestation of aortitis was sudden death. In each patient, there was extension of inflammation from the aorta into the atrioventricular node. These cases emphasize the importance of examining the conducting system in cases of sudden death associated with aortitis and no grossly evident cause of death. To our knowledge, this is the first report of aortitis presenting as sudden death. PMID- 1444748 TI - Architectural remodeling of lung allografts in acute and chronic rejection. AB - The mesenchymal and extracellular matrix alterations that occur in acute and chronic rejection of the lung allograft were studied immunohistochemically, utilizing a wide panel of antibodies. In early rejection, perivascular and peribronchiolar mononuclear infiltrates were associated with basement membrane disruption of the vessels and airways and an ingrowth of muscle-specific actin-, vimentin-positive, desmin-negative spindle cells accompanied by type IV collagenase-positive histiocytes. Subsequent fibrous scarring was manifested by perforation and reduplication of the basement membrane of airways and vessels and dense collagen deposition, primarily type III. As has been suggested in idiopathic pulmonary fibrosis, the fragmentation of basement membranes and the deposition of collagen IV and laminin by mesenchymal cells in vessels and airways may reflect the irreversible fibrosis responsible for allograft dysfunction. PMID- 1444749 TI - Mammary origin of metastases. Immunohistochemical determination. AB - Zinc-alpha 2-glycoprotein, gross cystic disease fluid protein 15, and estrogen receptors are expressed in a great proportion of breast carcinomas. These markers were investigated by immunohistochemistry in 28 metastases from breast carcinomas and for comparison on 24 metastases from other carcinomas. A group of 83 primary nonmammary tumors was also studied. Most (> 96%) breast carcinoma metastases expressed one or several markers, while all metastases of other origins were negative. This sensitive and apparently specific immunostaining proved to be of great utility in cases in which the mammary origin of metastases was difficult to establish. In four axillary lymph node metastases, it even led to the discovery of an occult homolateral breast carcinoma that was not detectable by clinical and mammographic investigations. This study indicates that the combined use of zinc alpha 2-glycoprotein, gross cystic disease fluid protein 15, and estrogenic receptors represents a useful immunostaining technique that can help the pathologist in determining the origin of breast carcinoma metastases. PMID- 1444750 TI - Uterine leiomyoblastoma (epithelioid leiomyoma) neoplasm of low-grade malignancy. A histopathologic study. AB - Uterine leiomyoblastomas are neoplasms of smooth muscle origin, which despite their benign histopathologic characteristics, have been shown to invade locally, metastasize, and recur, resulting in the patient's death. In an effort to define possible cellular changes that could explain the disparity between histopathologic features and biologic behavior, we have studied a series of three uterine leiomyoblastomas that, in routine sections, exhibited benign morphological characteristics. A detailed histopathologic study revealed, in all three cases, randomly distributed clusters of neoplastic cells with overt malignant features, such as cellular and nuclear atypia, abnormal mitoses, local infiltrating tendencies, and vascular invasion. These findings suggest that uterine leiomyoblastomas should be viewed as neoplasms of low-grade malignancy of a distinct clinicopathologic entity. PMID- 1444751 TI - Primary malignant melanoma of the urinary bladder. AB - Primary malignant melanoma is an unusual neoplasm in the urinary bladder that is infrequently found in association with melanosis. We report a case of bladder invasive malignant melanoma with melanosis in which the melanosis exhibited melanocytic atypia extending through to melanoma in situ and was diagnosed by immunohistochemical techniques using a monoclonal antibody, HMB-45. To our knowledge, such findings have not been reported previously. PMID- 1444752 TI - Primary carcinoid tumor of the urinary bladder. AB - A 62-year-old woman who presented with urinary frequency and microscopic hematuria was found to have a 1.2 x 1.0 x 0.6-cm polypoid carcinoid tumor of the urinary bladder. The tissue resected from the base after removal of the polypoid lesion disclosed a small focus of residual carcinoid tumor, associated with Brunn's epithelial nests, cystitis cystica, and cystitis glandularis. Tumor cells exhibited strong argyrophilia and weak argentaffinity. Immunohistochemical staining reactions were strongly positive for chromogranin and serotonin, and electron microscopy revealed characteristic dense-core granules. Flow cytometric evaluation revealed an aneuploid cell population with a DNA index of 1.20. PMID- 1444753 TI - Epidermal growth factor receptor expression in Barrett's esophagus. AB - Six cases of known Barrett's esophagus were examined immunohistochemically for the presence of epidermal growth factor receptor. All cases showed expression of epidermal growth factor receptor in intestinal metaplastic Barrett's epithelium, the most common form of Barrett's change. Expression of epidermal growth factor receptor may be important in neoplastic transformation in Barrett's esophagus, possibly by an autocrine mechanism. Alternatively, epidermal growth factor receptor expression in intestinal metaplastic Barrett's epithelium may represent a nonneoplastic regenerative phenomenon as seen at other sites within the gastrointestinal tract. Further larger studies are required to assess the clinical significance of these findings. PMID- 1444754 TI - Dissection of the aorta and coronary arteries associated with acute cocaine intoxication. AB - Acute myocardial ischemia, cardiac arrhythmias, and conduction disturbances are the most common cardiovascular complications of cocaine and its alkaloidal freebase "crack." Cocaine abuse-related acute aortic dissection has been reported only rarely: three cases in the last 5 years. Described herein, to our knowledge, is the first case of cocaine intoxication-associated acute aortic dissection that also involved the coronary arteries, causing sudden death. PMID- 1444755 TI - Eosinophil-mediated bile duct stricture. A case studied by immunohistochemistry. AB - Major basic protein accounts for the majority of the protein within the eosinophilic granule. Utilizing immunohistochemical staining for major basic protein, we have demonstrated the dominant role of the eosinophil in a reversible bile duct stricture. PMID- 1444756 TI - Nitroimidazoles, XIV: Synthesis of 4-nitroimidazoles with 1-substituents containing acid, ester or phenol functions, and radiosensitizing efficiency of some of these compounds. AB - 1,4-Dinitroimidazole and 1,4-dinitro-2-methylimidazole were reacted with aminocarboxylic acids and their esters, aminosulfonic acids, and aminophenol to obtain the corresponding 1-substituted-4-nitroimidazoles. The radiosensitizing efficiency of some esters of 2-(4-nitro-1-imidazolyl)alkanecarboxylic acids was tested. PMID- 1444757 TI - [Synthesis and cytostatic effect of 2-phenyl-3-alkyl(aryl)-2,3-dihydro 1,3,2(lambda-5)- benzoxazaphosphorine-4-one derivatives]. AB - Preparation of 2,3-dihydro-1,3,2-benzoxazaphosphorin-4-one derivatives and their 2-oxo derivatives is described. Compounds 1 and 12 have anticancer activity. PMID- 1444758 TI - Influence of [6S]-N5-formyltetrahydrofolic acid on the bioavailability of 5 fluorouracil combined with interferon-alpha-2b. PMID- 1444759 TI - [2-Amino-3-cyano-dihydroindol-5-ones. 2. The biological activity of a new class of compounds]. AB - 2-Amino-3-cyano-dihydroindol-5-ones 2 and 3 are formed by reaction of 2 Aminopyrrole-3-carbonitriles 1 with acetylenic acid esters. In various biological test systems they behave as cytotoxic agents. PMID- 1444760 TI - [2-Amino-3-cyano-dihydroindol-5-ones. 3. The chemical reactivity of a new class of compounds]. AB - The chemical reactivity of cytotoxic 5-indolone derivatives is examined in order to get ideas about their behaviour in biological systems. Dienone-phenol rearrangement preserving the indole ring system could not be achieved, aromatization of 1b gives the phenol derivative 3 alpha. In diluted NaOH ester hydrolysis occurs (1a,b----4a,b). Hydrolysis in conc. H2SO4 yields the amides 5a,b,d. In ethanolic HCl the ammonium salts 6a,b,d are formed. Acylation of 1a to 8 reveals the endocyclic N-atom as the nucleophilic center. Benzaldehyde being a strong electrophile adds to 1b in position 4. Weaker electrophiles such as dimethyl acetylenedicarboxylate (ADC) only react with the amides 5b,d to give 11 and 12. Nucleophiles (water, ethanol, n-propylamine) add to the delta 6-double bond yielding 14-16. PMID- 1444761 TI - Assessment of anti-HIV activity of some benzimidazolylthiazoles. AB - Benzimidazolylthiazoles 2 were synthesized by condensing 1H-benzimidazole-2 acetonitrile (1) with sulphur and isothiocyanates. The syntheses of the Schiff bases 3, thioureas 4, and thiazolopyrimido[1,6-a]benzimidazoles 5 and 6 are also described. Seven compounds were evaluated in vitro against human HIV, however, no significant activity was observed with any of these compounds. PMID- 1444762 TI - Studies on annelated [1,4]benzothiazines and [1,5]benzothiazepines, V. Synthesis and biological activity of N-2 alkylamino derivatives of 4,5-dihydro-s triazolo[3,4-d]-1,5-benzothiazepine. AB - The synthesis of a new series of N-2 alkylamino derivatives of 4,5-dihydro-s triazolo[3,4-d]-1,5-benzothiazepine has been accomplished starting from 2,3 dihydro-1,5-benzothiazepin-4(5H)ones and their 2-methyl and 2-aryl derivatives. All the compounds were tested in vitro for their antimicrobial activity, but none of them showed remarkable activity. The tricyclic compounds 7a-j, 8a-j, 9a-j, 10a j, and 11a-j were also screened for their CNS activity in mice and several of them showed interesting activity. PMID- 1444763 TI - Biotransformation of the sympathomimetic tetraminol in vitro. AB - On incubation with the postmitochondrial fraction of the liver homogenate of rabbits, guinea-pigs, rats, and mice in the presence of NADPH and oxygen, the alpha-sympathomimetic trans-3-(2-hydroxyethylamino)-5,8-dimethoxy-1,2,3,4 tetrahydro-2-n aphthol (Tetraminol, 1) is preferentially O-demethylated in position 8, yielding metabolite 3. In male rats O-demethylation is stronger than in females. PMID- 1444764 TI - [Enantioselective biotransformation of a new theophylline derivative]. AB - Reductive amination of 4 with (RS)-2 is an improved method to obtain 7-((RS)2 ((RS)-1-Methyl-2-phenyl-ethylamino)propyl)-theophylline (3) (ratio of diastereomers 1:1) compared with SN-displacement of proxyphyllintosylate with (RS)-2 (ratio of diastereomers 9:1). Due to steric hindrance 3 is no noteworthy prodrug for the intermediate formation of (RS)-2 in rats. The enantioselectivity of 2 after a single oral dose of 3 is determined in 24-h urine by HPLC on a Cyclobond-column using the isoindole derivatives, formed from o-phthalaldehyde, thioglycolic acid, and 2. The R(-)-amphetamine isomer is formed to a lesser amount (34.8%, range 32-37%) than the S(+)-isomer (65.2%, range 63-68%). PMID- 1444765 TI - Benzo[b]thiophenes, II: Novel benzo[b]thienylhydrazine and 1,3,4-oxadiazole derivatives as potential antidepressant agents. AB - Three novel series of benzo[b]thiophene derivatives bearing various hydrazone, hydrazine and 1,3,4-oxadiazole moieties were synthesized as potential antidepressant agents. 22 Compounds were evaluated for their in vitro inhibitory effect on monoamine oxidase enzyme (MAO) type A. Several compounds inhibited MAO stronger than pargyline hydrochloride. Maximum inhibitions of 83% and 90% were observed with 1-benzyl-2-(3-chlorobenzo[b]thienyl-2-carbonyl)hydrazine (24) and 1 [2-(4-chlorophenyl)ethyl]-2-(3-chlorobenzo[b]thienyl-2- carbonyl)hydrazine (35), respectively. PMID- 1444766 TI - New acylthiosemicarbazides, thiazolidinones, and 1,3,4-oxadiazoles as possible anticonvulsants. PMID- 1444767 TI - Urological long-term follow-up in women with spinal cord injuries. AB - One hundred eight women and 434 men admitted with spinal cord injuries between 1973 and 1987 were observed prospectively to determine the effects of age, sex, neurological classification, and method of bladder management method on renal function and urological complications. The primary method of bladder management for women throughout the study period was indwelling urethral catheterization as compared to condom drainage for their male counterparts. Renal function was determined by effective renal plasma flow and urological complications were determined by clinical symptoms and/or objective findings on intravenous pyelography (IVP). Analysis reveals that as in the general population advancing age and being female were significantly associated with lower ERPF (p < .05). Only in men were neurological classification (quadriplegia) and bladder management (ileoconduit) associated with significant decreases in ERPF (p < .05). Furthermore, women and men showed no significant differences in urological complication rates. From the data it can be concluded that there is no particular method of bladder management for women that necessarily leads to impaired renal function. PMID- 1444768 TI - Subscapular nerve block in the painful hemiplegic shoulder. AB - Shoulder pain frequently superimposes substantial disability on a limb already limited by hemiplegia. The subscapularis muscle is a major internal rotator of the shoulder and, therefore, plays a role in the flexor synergy pattern commonly seen in spastic hemiplegia. Thirteen patients with spastic hemiplegia, limited range of motion, and painful shoulders underwent percutaneous phenol blocks to the nerves to the subscapularis. Patients' ages ranged from 22 to 76 (x 46 years) and the duration of hemiplegia from two to 13 months. Immediate and significant (p < 0.01) improvements in range of motion were observed in abduction (21 degrees), flexion (40 degrees), and external rotation (38 degrees). Relief of pain was also noted with the previously painful movement. Subscapularis nerve block is a new and potentially useful technique in the management of the painful hemiplegic shoulder. PMID- 1444769 TI - Phenol block for hip flexor muscle spasticity under ultrasonic monitoring. AB - Hip flexor spasticity, which is often associated with central nervous system (CNS) diseases, is a major impediment in rehabilitation. In order to cope with this problem, lumbar nerve blocking techniques developed by Meelhuysen and major and minor psoas muscle blocking techniques developed by Awad have been used in combination with physical therapies. Based on these techniques, we conducted major and minor psoas muscle phenol block (motor point block or intramuscular nerve block) under ultrasonic monitoring. Phenol block was conducted in nine patients with cerebral infarction (13 blocking procedures) and three with spinal cord injuries (six blocking procedures) while keeping them in a lateral position with the operation side upside. The beginning of the femoral nerves and part of the lumbar artery were visualized by ultrasound in some patients. As a result of the improvement of hip flexor spasticity, the range of hip joint motion (determined by the Mundale technique, prone hip extension and Thomas test) improved shortly after blocking. When physical therapy was conducted after blocking, improvement of skin care management was observed in eight cases, ability to keep in a stable sitting position in nine, improvement of a standing posture in three, increases in the ability to walk in two and alleviation of pain in three. Although nerve block is reported to result in hematoma, decreases in muscle force, pain, cystic/rectal disorders and hypogonadism, we have observed no such complication in our patients. PMID- 1444770 TI - Associated movement in hemiplegia: the effects of force exerted, limb usage and inhibitory training. AB - The intensity of associated movement or motor overflow in the contralateral limb during a unimanual task was evaluated in postacute traumatic brain injured (TBI) young adults with left side hemiplegia and age-matched controls. Both groups demonstrated increased overflow with increasing active limb force, although the trend was for greater overflow to occur in the TBI group, particularly when the spastic limb was active. Following three successive days of inhibitory training with electromyographic feedback, TBI subjects were able to significantly reduce the amount of overflow in the contralateral limb, greater inhibition occurring in the noninvolved limb during spastic limb movement. The results are discussed in terms of a dual model of inhibitory control and the role of such processes in uncoupling the limbs for independent limb usage. PMID- 1444771 TI - Negative transfer of training following brief practice of elbow tracking movements with electromyographic feedback from spastic antagonists. AB - This study aimed to overcome gaps in the literature by investigating effects of EMG feedback provided specifically from spastic muscles during antagonist phases of active movement, while controlling for the effects of practicing the movement and while testing for transfer of training without confounding several transfer phenomena. In a single training session, two groups of stroke patients practiced a pursuit tracking task by following a moving target with elbow flexion and extension, simultaneously attempting to reduce the activity of elbow flexors. Both groups tracked the target more accurately following training. Transfer tests failed to demonstrate effects of feedback on accuracy of tracking or on electromyographic activity during performance of the practiced task without feedback. Moreover, the group that was trained with electromyographic feedback exhibited negative transfer on variants of the practiced task: tracking faster or less predictable targets. PMID- 1444772 TI - Concentric versus combined concentric-eccentric isokinetic training programs: effect on peak torque of human quadriceps femoris muscle. AB - To determine the effects of isokinetic resistance training of the quadriceps, 25 male volunteers were randomly assigned to five training groups: Concentric Slow (CS), Concentric Fast (CF), Concentric-Eccentric Slow (MS), Concentric-Eccentric Fast (MF), and Control (C). In training, subjects performed 20 contractions of each quadriceps using either 60 degrees/sec or 180 degrees/sec, for both sides, five days per week for 12 weeks. Testing consisted of measurement of peak torque, at intervals of 60 degrees/sec across a spectrum of velocities ranging from plus to minus 240 degrees/sec, at 0, 4, 8, and 12 weeks. Repeated MANOVA using planned comparisons showed that all trained subjects made significant peak torque gains (p < .05), but that the gains made by MS and MF were greater. These findings suggest that the addition of an eccentric training component to a concentric isokinetic training program may allow greater peak torque gains regardless of the velocity. PMID- 1444773 TI - Relationship between two measures of upper extremity strength: manual muscle test compared to hand-held myometry. AB - One hundred and twenty-two individuals with spinal cord injuries at levels C4-6, Frankel classifications A through D, were evaluated to determine the relationship between the manual muscle test (MMT) and hand-held myometry as accurate methods for measuring muscular strength. More specifically, this study attempted to define a range of myometry scores that could be correlated with discrete MMT grades. It also investigated which of the two modalities (MMT or hand-held myometry) is the best reflection of improvement in muscle strength over time. Sequential motor strength examinations using both modalities were performed at 72 hours, one week, and two weeks post SCI and then one, two, three, four, six, 12, 18, and 24 months post injury. The data analyses included calculations of Spearman ranked correlations, analyses of variance, and linear regressions. Results showed that 22 of 24 correlations between MMT and myometry were significant at p values less than .001. The range of myometry measurements for a particular MMT grade appears to be most specific for MMT scores less than 4 (ie, poor-plus to good), and less specific for MMT scores greater than or equal to 4. The results of this study also indicate that myometry measurements detect increases in strength over time, which are not reflected by changes in MMT scores. PMID- 1444774 TI - Osteoarthritis of the hand and wrist in the post poliomyelitis population. AB - People with a chronic motor disability of the legs become increasingly more dependent upon their upper limbs for mobility and self-care skills as they age. Many of them complain of hand and wrist pain. A cross-sectional study of 61 post poliomyelitis survivors was done to determine the prevalence of osteoarthritis within this population and to determine any inherent risk factors. Each subject underwent a radiographic evaluation of both hands and wrist as well as a detailed physical examination. A questionnaire was used to ascertain a history of hand activity, use of canes/crutches, walkers and wheelchairs. The mean age of the population sample was 49 +/- 6 with a mean duration of disability of 35 +/- 4 years. The prevalence of moderate or severe osteoarthritis of either the hand or wrist was 13% whereas the prevalence was 68% when cases with mild arthritic changes were also included. The risk factors associated with hand and wrist osteoarthritis in this population included age, lower limb weakness, use of an assistive devices, and severity of disability. PMID- 1444775 TI - Clinical and laboratory measures of postural balance in an elderly population. AB - The objective of this cross-sectional study was to compare scores on the Balance Scale with laboratory measures of postural sway and other clinical measures of balance and mobility. Thirty-one elderly subjects were assessed on the clinical measures and the laboratory tests of postural sway while standing still and in response to pseudorandom movements of the platform. The average correlation between the Balance Scale and the spontaneous sway measures was -.55. It was slightly lower (r = -.38) for the same parameters measured during the pseudorandom tests. There were high correlations between the Balance Scale and the Balance Sub-Scale developed by Tinetti (r = .91), Barthel Mobility sub-scale (r = .67), and timed "Up and Go" (r = -.76). The Balance Scale was the most efficient measure (effect size > 1) to statistically discriminate between subjects according to their use of each type of mobility aide (walker, cane, no aids). These data contribute to existing information on the performance of the Balance Scale and supports the validity of the Balance Scale in this geriatric population. PMID- 1444776 TI - Aerobic capacity with two leg work versus one leg plus both arms work in men with peripheral vascular disease. AB - The purpose of this pilot study was to examine the correlation between ergometry in men with peripheral vascular disease exercising with both legs and with one leg and both arms. Fifteen men with peripheral vascular disease performed three symptom-limited exercise tests on an ergometer that could be operated from a wheelchair with both legs or with one leg and both arms. The three exercise conditions were both legs (arms stabilized), left leg plus both arms, and right leg plus both arms. The exercise parameters compared were maximum oxygen consumption, maximum heart rate, and duration of exercise. Blood pressure was monitored at two-minute intervals and oxygen saturation and electrocardiogram were monitored continuously. The mean VO2 max +/- standard deviation for both legs, right leg plus both arms, and left leg plus both arms were 14.36 +/- 6.15, 14.86 +/- 4.09, 14.01 +/- 4.14 ml O2/kg-min, respectively. The mean duration of exercise +/- standard deviation were 12.01 +/- 5.74, 10.94 +/- 4.68, and 9.81 +/- 4.70 minutes respectively. The mean maximum heart rate +/- standard deviation were 126 +/- 24, 137 +/- 23, 136 +/- 23, respectively for the same exercise conditions. The Pearson Correlation Coefficients for VO2 for both legs versus right leg plus both arms and left leg plus both arms were .639 and .873, respectively. The Pearson Correlation Coefficients for duration of exercise for both legs versus right leg plus both arms and left leg plus both arms were .837 and .877, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444777 TI - Functional electrical stimulation leg cycle ergometer exercise: training effects on cardiorespiratory responses of spinal cord injured subjects at rest and during submaximal exercise. AB - This study investigated the cardiorespiratory (CR) responses at rest and during submaximal (0-W) functional electrical stimulation (FES)-induced leg cycle ergometer (LCE) exercise prior to and following a progressive intensity FES-LCEa exercise training program in spinal cord injured (SCI) subjects. Seven quadriplegics and six paraplegics participated in FES-LCE training three sessions per week for approximately 12 weeks (36 sessions). Monitored CR responses, including oxygen uptake (VO2), pulmonary ventilation (VE), respiratory exchange ratio (RER), arteriovenous O2 difference (a-vO2), blood pressure (BP), heart rate (HR), stroke volume (SV), total peripheral resistance (TPR), and cardiac output (Q), were determined before and after training. Power output (PO) increased significantly (p < .05) over the duration of the training program, indicating increased in strength and endurance of the paralyzed muscles used. Respiratory responses were not significantly altered by training in both groups. FES-LCE training significantly increased resting HR and SBP in quadriplegics and lowered SBP, DBP, and MAP in paraplegics. In both groups, HR and BP during submaximal exercise significantly decreased and SV and Q significantly increased after completion of the training program. These results suggest that FES-LCE training improves peripheral muscular and central cardiovascular fitness in SCI subjects. Posttraining HR and BP may also be more stable in quadriplegics and alleviate hypotension. This therapeutic exercise may ultimately lead to improved rehabilitation outcome and reduced stress during activities of daily living, and possibly reduce the risks for secondary CR disabilities. PMID- 1444778 TI - Heterotopic ossification in children with burns: two case reports. AB - Heterotopic ossification is the formation of ectopic bone in soft tissue, and has been reported as a rare complication in pediatric burn patients. At our hospital, two 86% body surface area burn patients developed heterotopic ossification in the shoulder, elbows, distal femur, proximal tibia, fibula, and ribs approximately four months after the burn injury. These two rare and unusual cases are presented documenting the clinical involvement, radiological studies, laboratory data, as well as treatment of their heterotopic ossification. Discussion will focus on the incidence, diagnosis, pathophysiology, and treatment of heterotopic ossification in burn patients and how this information relates to the specific diagnosis and management of the complication of heterotopic ossification in the burn child. PMID- 1444779 TI - Suprascapular neuropathy during progressive resistive exercises in a cardiac rehabilitation program. AB - A 56-year-old man developed left shoulder pain three weeks after starting a cardiac rehabilitation program, which consisted of submaximal aerobic and progressive resistive exercises. Pain in the left shoulder intensified and weakness developed one week later. He sought medical attention ten weeks after the onset. Physical examination showed only weakness of left shoulder abduction and external rotation with mild atrophy of the left supraspinatus and infraspinatus muscles. Electrodiagnostic study showed fibrillation potentials and positive sharp waves in the left supraspinatus and infraspinatus muscles with delayed conduction to the supraspinatus. The left suprascapular notch was injected with local steroid. Within one week, improvement occurred, and one month later the patient was pain free and stronger. The motor latency returned to normal, and no fibrillations nor positive waves were seen. The patient returned to his previous functional level. Suprascapular neuropathy should be considered as a cause of shoulder pain and weakness in a person involved in any strengthening exercise program. A steroid injection of the suprascapular notch performed early may avoid the need for surgery. PMID- 1444780 TI - Anterior tarsal tunnel syndrome. AB - Anterior tarsal tunnel syndrome is a rarely reported entrapment neuropathy of the deep peroneal nerve under the extensor retinaculum at the ankle. The roof of the tunnel is the inferior extensor retinaculum. The floor is the fascia overlying the talus and navicular. Within the tunnel are four tendons, an artery, a vein, and the deep peroneal nerve. Two patients with foot pain and dysesthesias had prolonged peroneal distal latencies with reduced amplitudes from the extensor digitorum brevis (EDB). Electromyographic (EMG) abnormalities were confined to the EDB. Both patients underwent surgical decompression of the anterior tarsal tunnel with reduction of their pain and dysesthesias. If present, an accessory peroneal nerve, which does not go through the tunnel, can mask EMG findings in the EDB. Diagnosing anterior tarsal tunnel syndrome can also be difficult if there is a tendency to assume that fibrillation potentials in the EDB are due to shoe wear and prolonged peroneal latencies to cool extremities. PMID- 1444781 TI - An alternative bent-knee prosthesis. AB - Prosthetic fitting in patients with below-knee amputations and concurrent knee flexion contractures poses inherent difficulties to the prosthetic rehabilitation team. The standard bent-knee prosthesis is bulky and awkward. It treats the patient functionally as a knee disarticulation and yields no potential for improving the patient's degree of contracture. This paper describes a case report with an alternative to the bent-knee prosthesis that not only offered improved function relative to the standard bent-knee prosthesis, but also acted therapeutically by reducing the patient's knee-flexion contracture. PMID- 1444782 TI - Relegating "CVA" to the dust bin. PMID- 1444783 TI - Laparoscopic surgery. A difference. PMID- 1444784 TI - Laparoscopic hernia repair. The socioeconomic tyranny of surgical technology. PMID- 1444785 TI - Surgical oncology in the 21st century. PMID- 1444786 TI - Extended indications for functional limb-sparing surgery in extremity sarcoma using complex reconstruction. AB - From 1980 to 1991, 29 patients underwent complex reconstruction following extremity sarcoma resection. Soft tissue was the site of origin in 15 patients (52%) and bone was the site of origin in 14 patients (48%), with 20 sarcomas (69%) in the lower extremity. Resection consisted of the following procedures: extended anatomical soft-tissue resections (21 patients [72%]), bone resections (18 patients [62%]), and joint resections (14 patients [48%]). Reconstruction involved the following: myocutaneous flaps (20 patients [69%]), joint prosthesis (eight patients [28%]), and bone reconstruction (15 patients [52%]). There was no surgical mortality; one patient required an amputation owing to surgical complications. The site of the first failure was local (four [31%] of 13 patients), lung (five patients [38%]), others (four patients [31%]). At a median follow-up of 23 months, 18 patients (62%) had no evidence of disease, 27 (93%) had no local disease, 21 (72%) had good extremity function, three (10%) had major disabilities, and five (17%) underwent amputations. Local control improved when the margin of resection was larger than 10 mm. Disease-free survival was 67% at 3 years. Overall survival was 51% at 5 years. Tumor size was an independent predictor of overall survival. Local recurrence did not affect overall survival. PMID- 1444787 TI - Pulmonary resection for metastatic breast cancer. AB - Thirty-three patients treated primarily with surgical excision of pulmonary metastases from breast cancer were compared with 30 patients treated primarily with systemic chemohormonal therapy. Treatment for patients in the surgical group included pulmonary resection alone in 20, resection plus adjuvant systemic therapy in nine, and resection plus adjuvant radiation therapy in four. Treatment for patients in the medical group included systemic therapy alone in 22 and systemic therapy plus local radiation therapy in eight. Mean survival in the surgical group was significantly longer than that in the medical group, even when only those patients who manifested single pulmonary nodules were compared (58 months vs 34 months). The overall 5-year survival rate after treatment of lung metastasis was significantly greater for the surgical group than for the medical group (36% vs 11%). The results of this study indicate that surgical resection should be considered in patients with breast cancer who develop operable pulmonary metastases without evidence for concomitant extrapulmonary disease. In selected patients, such therapy may result in a survival benefit. PMID- 1444788 TI - Management of small soft-tissue sarcoma of the extremity in adults. AB - To determine the significance of small (< or = 5 cm in diameter) soft-tissue sarcoma of the extremity, 174 adult patients were identified from information that had been entered prospectively into a database of 1742 patients between July 1982 and December 1990. Median follow-up was 48 months. The majority of tumors were high grade (n = 114; 66%). Local recurrence (n = 17) was seen in patients with both high-grade (11%) and low-grade tumors (7%). Distant metastases were seen in 7% of high-grade tumors and in no low-grade tumors. The overall 5-year survival rate was 94% for all patients. Grade, depth, location, type of operation, and sex did not affect 5-year survival or local recurrence-free survival. Neither postoperative adjuvant chemotherapy nor radiation therapy resulted in superior 5-year survival or local recurrence-free survival when compared with no postoperative treatment. The prognosis of these lesions is favorable, and no additional prognostic factors were identified. Inclusion of these patients into adjuvant therapy trials examining survival is inappropriate. PMID- 1444789 TI - The James Ewing Lecture. PMID- 1444790 TI - Molecular surgery for cancer. AB - Advances in the understanding of the process of carcinogenesis may allow prevention, diagnosis, and treatment of cancer to be approached at the molecular level. Studies in our laboratory show that growth factors (transforming growth factor alpha), dominant oncogenes (HER-2/erb B2 and K-ras), and tumor suppressor genes (p53) are functionally important in the maintenance of the malignant phenotype of human non-small-cell lung cancer cells. Application of these findings to clinical problems include the identification of p53 mutations as markers for malignant change in Barrett's epithelium, the use of discordant p53 mutations to diagnose second primary malignant neoplasms in patients with head and neck cancer, and the potential for therapy by the reversal of genetic lesions. PMID- 1444791 TI - Relationship between disease-free interval and survival in patients with recurrent melanoma. AB - A total of 2468 patients with recurrent melanoma were subdivided on the basis of disease-free interval: group 1 had recurrences within 1 year (n = 810), group 2 at years 1 to 3 (n = 1001), group 3 at years 3 to 5 (n = 363), group 4 at years 5 to 10 (n = 329), and group 5 after 10 years (n = 145). Ten-year survivals were 21%, 23%, 25%, 28%, and 35%, respectively. Patients who had recurrences within 1 year had a decreased median survival compared with those who had later recurrences, although the differences were not clinically significant (only 6 to 8 months). Survival was improved for the few patients who had recurrences longer than 10 years from diagnosis. However, for the majority of patients, who had recurrences between 1 and 10 years, the disease-free interval did not predict subsequent survival. The data support the hypothesis that malignant cells can exist in a state of relative quiescence for extended periods. Once disease reactivation occurs, however, the subsequent survival is relatively predictable and is independent of the initial period of tumor dormancy. PMID- 1444792 TI - The natural history of mammographic calcifications subjected to interval follow up. AB - The purpose of this investigation was to determine the natural history and risk of malignancy associated with isolated indeterminate microcalcifications subjected to interval follow-up. During a 2-year study, 91 patients were identified with indeterminate microcalcifications alone. Specific roentgenographic features of the calcifications were evaluated on initial and follow-up mammograms. During a mean follow-up of 36 months, 19 (21%) of the women exhibited mammographic changes. Ten patients (11%) with suspicious changes underwent a needle-directed biopsy 6 to 30 months after the initial mammographic screening. Five women (5.5%) were diagnosed as having breast carcinoma; three had invasive ductal carcinoma and two had purely intraductal lesions. Four patients had axillary lymph node dissections and no metastatic disease was found. We found no significant differences in the roentgenographic features associated with malignant vs benign lesions apart from an increased overall estimation of the probability of malignancy rating in the five patients with breast carcinoma. We recommend that patients be followed up with mammography at regular intervals for at least 18 months following recognition of indeterminate microcalcifications. PMID- 1444793 TI - Effect of supplemental dietary glutamine on methotrexate concentrations in tumors. AB - This study evaluated the effects of supplemental dietary glutamine (GLN) on methotrexate sodium concentrations in tumors and serum of sarcoma-bearing rats following the initiation of methotrexate. After randomization to a GLN diet (+GLN) or GLN-free diet (-GLN), tumor-bearing rats received 20 mg/kg of methotrexate sodium by intraperitoneal injection. The provision of supplemental GLN in the diet increased methotrexate concentrations in tumor tissues at 24 and 48 hours (38.0 +/- 0.20 nmol/g for the +GLN group vs 28.8 +/- 0.10 nmol/g for the -GLN group and 35.6 +/- 0.18 nmol/g for the +GLN group vs 32.5 +/- 0.16 nmol/g for the -GLN group, respectively). Arterial methotrexate levels were elevated only at 48 hours (0.147 +/- 0.007 microns/L for the +GLN group vs 0.120 +/- 0.006 microns/L for the -GLN group). Tumor morphometrics were not different between the groups but significantly greater tumor volume loss was seen even at 24 hours ( 2.41 +/- 1.3 cm3 for the +GLN group vs -0.016 +/- 0.9 cm3 for the -GLN group). Tumor glutaminase activity was suppressed in both groups at 48 hours, but more so in the +GLN group (0.94 +/- 0.13 mumol/g per hour for the +GLN group vs 1.47 +/- 0.22 mumol/g per hour for the -GLN group). This study suggests that GLN may have therapeutic as well as nutritional benefit in oncology patients. PMID- 1444794 TI - 99mTc-IMMU-4 monoclonal antibody scan in colorectal cancer. A prospective study. AB - A blinded prospective study of 34 patients with colorectal adenocarcinoma using the Fab' fragment of the anticarcinoembryonic antigen monoclonal antibody type IMMU-4 labeled with technetium 99m was conducted to compare, on a lesion-by lesion basis, the findings of radioimmunoscintigraphy, preoperative computed tomography, and exploratory celiotomy. Of 115 lesions detected at surgery, 113 were adenocarcinoma. Radioimmunoscintigraphy detected 59 lesions and computed tomography detected 62; both studies combined detected 72. Twenty-nine (54%) lesions missed by radioimmunoscintigraphy and 24 (45%) missed by computed tomography were 1 cm or smaller. When both studies were combined, the sensitivities were 90%, 24%, and 42%, and the specificities were 52%, 86%, and 61% for hepatic, extrahepatic intra-abdominal, and pelvic lesions, respectively. In 10 patients, additional information obtained with the radioimmunoscintigram could have altered the treatment of these patients. In this study, radioimmunodetection scan was complementary to computed tomographic scan in the examination of patients with colorectal carcinoma. PMID- 1444795 TI - Hepatic metastasis alters the immune function of murine liver nonparenchymal cells. AB - To examine the effect of a single hepatic focus of metastatic colon tumor on the immune function of liver non-parenchymal cells (NPCs) from C57Bl/6 mice, we injected 2.5 x 10(5) liver-derived murine colon adenocarcinoma (LD-MCA-38) cells beneath the liver capsule. Three weeks following injection of the tumor cells, the immune function of the NPCs was studied. The NPCs from tumor-bearing mice exhibited increased cytotoxic and proliferative activity. The NPCs from tumor bearing mice also contained a greater percentage of CD8+ and T-cell receptor gamma/delta+ liver-associated T lymphocytes. Levels of interleukin 6 and tumor necrosis factor were increased in the NPC supernatant, and interleukin 6 levels were increased in serum from tumor-bearing mice. We conclude that the presence of a single hepatic focus of metastatic tumor results in augmented immune function of murine liver NPCs. PMID- 1444796 TI - Cholera toxin pretreatment protects against tumor necrosis factor lethality without compromising tumor response to therapy. AB - Antitumor therapy with tumor necrosis factor is limited by systemic toxic effects. We studied whether cholera toxin, a bacterial exotoxin that adenosine diphosphate-ribosylates the alpha-subunit of Gs proteins, could separate the lethal from the antitumor effects of tumor necrosis factor. A single dose of intravenous cholera toxin protected non-tumor-bearing mice from a lethal dose of Escherichia coli endotoxin administered 6 or 24 hours later. On the basis of these results, tumor-bearing mice were randomized to receive either cholera toxin or saline, followed 6 hours later by either human tumor necrosis factor (400 micrograms/kg) or saline. Tumor-bearing mice pretreated with cholera toxin had (1) reduced treatment-related mortality (0/11 vs 5/11 for saline controls) and (2) tumor regression similar to that of controls. In a separate experiment in tumor-bearing mice, intravenous human tumor necrosis factor treatment induced an increase in serum levels of murine tumor necrosis factor to a peak of 500 pg/mL at 1 hour in saline-pretreated controls, while a similar increase could not be detected in those mice pretreated with cholera toxin. These results suggest that pretreatment with cholera toxin can reduce the endogenous tumor necrosis factor response to administered tumor necrosis factor and separate the lethal from the antitumor effects. Cholera toxin may prove to be a useful tool for investigating the mechanisms underlying the varied effects of tumor necrosis factor. PMID- 1444797 TI - Surgical resection following interleukin 2 therapy for metastatic renal cell carcinoma prolongs remission. AB - Records of 399 patients with metastatic renal cell carcinoma treated with interleukin 2 with or without lymphokine-activated killer cell immunotherapy enrolled in 14 separate clinical trials from multiple institutions were reviewed to determine whether patients with a partial response to interleukin 2 therapy would benefit from surgical resection of residual tumor. Sixty-two patients demonstrated objective responses (15.5%), 18 (4.5%) complete and 44 (11.0%) partial. Eleven patients underwent resection of residual tumor in the lung, kidney, retroperitoneum, or pelvis so that they had "surgically no evidence of disease" (SNED). Of these, 10 had partial responses, and one patient with progressive disease had a complete response. Comparison of response duration showed no difference between the complete response and SNED groups, but there was a significant difference between each of these groups and the partial response group. At this writing, all 11 patients in the SNED group remained alive without evidence of disease (median follow-up, 21 months). In contrast, only 14 patients (76%) with complete responses and 15 patients (35%) with partial responses remained free of disease progression. Enhanced survival of the complete response and SNED groups compared with the partial response group borders on significance and awaits longer follow-up. These data suggest that surgical resection, if technically feasible, may benefit patients who show a partial response to interleukin 2 treatment for metastatic renal cell carcinoma. PMID- 1444798 TI - Surgical glove powders bind latex antigens. AB - Latex surgical gloves have recently been identified as a potential source of allergens. Much of the current information suggests that the soluble proteins in latex may cause significant reactions in sensitive individuals. The starch powders used as a lubricant on some latex gloves have also been identified as potential allergens in some patients. In this study, we determined these powders to act as potential carriers of latex allergens. We have produced a polyclonal antiserum to be used as a reagent to study latex proteins. By Western blot analysis, we identified a significant interaction between latex proteins and starch powders. The binding of latex proteins to starch particles results in a glove particle that may have an increased potential to act as an allergen. The latex protein-starch particles represent a potential mechanism for exposure and sensitization of health care workers to latex allergens. Elimination of these particles from the operating room should reduce the route of sensitization and the potential for adverse reactions to latex. PMID- 1444799 TI - A new procedure for management of extrahepatic portal obstruction. Proximal splenic-left intrahepatic portal shunt. AB - For management of obstruction of the extrahepatic portal trunk in patients with healthy livers, we designed an end-to-side anastomosis between the proximal splenic vein and the umbilical portion of the left intrahepatic portal vein and performed a splenectomy to relieve portal hypertension, treat hypersplenism, and restore hepatic portal flow. To our knowledge, no other procedure more adeptly restores original hepatic blood flow. Creation of an anastomosis between the coronary vein and umbilical portion of the left intrahepatic portal vein is an alternative method. PMID- 1444800 TI - Massive intra-abdominal hemorrhage from a hepatic laceration caused by vomiting. AB - We present a case report of a previously undocumented incident of massive hemoperitoneum from a liver laceration secondary to vomiting. The patient presented with the complaint of vomiting and abdominal pain. Computed tomography revealed perihepatic and perisplenic fluid collections. With this evidence and a rapidly falling hematocrit, she underwent emergency laparotomy. Intraoperative findings included 3 L of blood in the abdomen and a liver laceration at the juncture of the liver and the falciform ligament. PMID- 1444801 TI - Studies on the prenatal toxicity of toluene in rabbits following inhalation exposure and proposal of a pregnancy guidance value. AB - Prenatal toxicity of toluene was determined in two separate studies by inhalation exposure of Himalayan rabbits. In the first study 15 artificially inseminated females per group were exposed to 30, 100, or 300 ppm and in the second study 20 artificially inseminated females per group inhaled 100 or 500 ppm. In each case the rabbits were exposed for 6 hours per day from day 6 post-insemination (p.i.) to day 18 p.i. The respective controls inhaled conditioned clean air under the same exposure conditions. No signs of maternal toxicity were observed. All data obtained on gestational parameters were found to be within the variation range reported for this rabbit strain. The fetal external, soft tissue and skeletal findings were seen in toluene exposed fetuses in a frequency similar to the corresponding and/or historical controls. Differences observed between the groups were not concentration dependent and were considered incidental rather than compound related. Therefore, toluene was not embryotoxic, fetotoxic, or teratogenic for rabbits exposed during the period of organogenesis. The highest concentration tested under these conditions (500 ppm) was found to be a no observable-adverse-effect level (NOAEL) for both the adult and the fetal Himalayan rabbit. Based on these and previous results of animal studies of prenatal toxicity, a safety or uncertainty factor approach is considered for setting limits of exposure for women at workplaces. A pregnancy guidance value of 20 ppm is proposed. PMID- 1444802 TI - Auditory degeneration after exposure to toluene in two genotypes of mice. AB - Two inbred strains of mice, CBA/Ca (with a moderate hearing loss starting late in life) and C57BL/6J (with an early onset of spontaneous auditory degeneration), were exposed to toluene by inhalation (1000 ppm, 12 h/day, 7 days) at either 1 or 6 months of age. Thresholds of auditory brainstem response (ABR) were measured 3 5 days after exposure and assessed repeatedly up to the age of 16 months (C57) or 23 months (CBA). Both strains of mice exposed to toluene at 1 month of age showed a mild loss of sensitivity at a high frequency (31.5 kHz) shortly after exposure. With increasing age, toluene exposure had little effect on the aging process of the auditory system in CBA mice but accelerated age-related hearing loss in C57 mice. The results indicate that toluene exposure can aggravate auditory deterioration only in mice with a strong genetic predisposition to spontaneously precocious age-related hearing loss. PMID- 1444803 TI - Effects of p,p'-DDE and some other chlorinated hydrocarbons on the formation of prostaglandins by the avian eggshell gland mucosa. AB - Some structurally related chlorinated hydrocarbons were investigated for their effects on the production of prostaglandins by the eggshell gland mucosa of ducks and domestic fowl. Formation of PGF2 alpha, PGE2 and TxB2 by homogenates of domestic fowl eggshell gland mucosa was significantly inhibited by in vitro addition of p,p'-DDE, Arochlor 1242 and, to a lesser extent, Arochlor 1260, but not by p,p'-DDT and o,p'-DDE. Comparatively, in duck eggshell gland mucosa homogenates, synthesis of the same prostaglandins was somewhat more sensitive to inhibition by 5 microM p,p'-DDE added in vitro. Eggshell gland mucosa synthesized significantly more PGF2 alpha, PGE2 and TxB2 than did the mucosa of the magnum and isthmus regions of the oviduct. Duck eggshell gland mucosa homogenates synthesized significantly more prostaglandins than similar homogenates from the domestic fowl, and, considering the former synthesis of PGF2 alpha was significantly higher when ducks were slaughtered at 08:00 than at 16:00 hours. In ducks, dietary administration of 40 ppm, p,p'-DDE for 45 days resulted in 21% eggshell thinning compared to the contemporary control values. This treatment also resulted in notable effects in homogenates of the eggshell gland mucosa, as compared to controls: Ca2+ uptake was reduced by 43%, synthesis of PGF2 alpha, PGE2 and TxB2 was reduced by 26%, 38% and 53%, respectively; the Ca content was increased to 145%. The role of p,p'-DDE in inhibiting prostaglandin formation in the eggshell gland is discussed as a mechanism of the eggshell thinning action of this chlorinated hydrocarbon. PMID- 1444804 TI - Manganese induced brain lesions in Macaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging. AB - A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [11C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [11C]-raclopride, demonstrating D2 dopamine receptors, and [11C]-L-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [11C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [11C]-L-dopa decarboxylation was not significantly altered indicating a sparing of [11C]-L-dopa decarboxylation during manganese poisoning. A transient decrease of [11C]-raclopride binding occurred but at the end of the study D2-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i.e. before a reversal of the manganese accumulation. PMID- 1444805 TI - Paracetamol toxicity in hamster isolated hepatocytes: the increase in cytosolic calcium accompanies, rather than precedes, loss of viability. AB - Paracetamol is cytotoxic to hamster isolated hepatocytes by a mechanism that does not involve an early increase in [Ca2+]i. Although an increase in [Ca2+]i does occur, it accompanies rather than precedes, loss of viability. Studies with the ionophore, 4-bromo-A23187, suggest that although sustained elevations of [Ca2+]i per se can initiate cell death, this occurs at levels of [Ca2+]i only above 500 nM. This concentration was not achieved on exposure of cells to a cytotoxic concentration of paracetamol for 30 min. The [Ca2+]i-response of hepatocytes to vasopressin stimulation was not altered by exposing the cells to toxic concentrations of paracetamol. This demonstrates that paracetamol does not cause any impairment in the mobilisation or redistribution of Ca2+. The role of elevated levels of [Ca2+]i in mediating chemically-induced cell-killing requires re-evaluation. PMID- 1444806 TI - Effects of the oxazolidinedione anticonvulsants trimethadione and dimethadione and the barbiturate homolog 5,5-dimethylbarbituric acid on N-nitrosodiethylamine initiated renal and hepatic carcinogenesis in the F344/NCr rat. AB - The oxazolidinedione anticonvulsant trimethadione (3,5,5-trimethyl-2,4 oxazolidinedione, TMO) as well as its major metabolite, dimethadione (5,5 dimethyl-2,4-oxazolidinedione, DMO), and a structural analog from the barbiturate series, 5,5-dimethylbarbituric acid (DMB), were fed to F344/NCr male rats previously given a single initiating injection of N-nitrosodiethylamine (NDEA). The known promoter, phenobarbital (5-ethyl-5-phenylbarbituric acid, PB), was employed in this study as a positive control. At dosage levels equimolar to 500 ppm PB, none of the three compounds promoted development of hepatocellular adenomas or carcinomas, in contrast to PB. The two oxazolidinedione analogs and DMB caused minimal or no induction of cytochrome P450 isozyme 2B1 (CYP2B1) mediated alkoxyresorufin O-dealkylase activities following short-term (2 weeks) feeding to separate groups of 6-week-old male F344/NCr rats, in contrast to the dramatic induction caused by PB. Promotion of neither thyroid nor renal neoplasia was observed following prolonged feeding of any of the tested compounds, although a significantly higher frequency of premalignant renal cortical tubular lesions (dysplasias) was seen in rats exposed to TMO following NDEA initiation than in those treated with NDEA alone. These studies provide important additional data on structure/liver tumor promoting activity relationships, and yield further evidence that within this group of structurally related anticonvulsants, it is possible to separate anticonvulsant activity from tumor promoting activity in the rat liver. PMID- 1444807 TI - Acute infection of mice with highly virulent group B streptococci as a host resistance model for immunotoxicity assessment. AB - This report describes a unique model for immunotoxicity evaluation in mice. The model is adapted from previously described mouse models for group B streptococcus (GBS) infections in human neonates. In this disease as well as a number of human diseases caused by highly virulent pathogens, the mechanisms of innate immunity are unable to protect the host, and survival is strictly dependent on acquired immunity. Unlike other host resistance models widely used in immunotoxicity studies, the GBS model utilizes bacteria that are highly virulent for mice (LD50 = 5-17 colony forming units). GBS is not virulent for adult humans and can be safely handled with typical precautions. Acquired immunity in the GBS model is induced during a 2 week period by two injections of heat-killed GBS. The immunizing doses are the minimum which will allow survival of 80-100% of mice in response to challenge with an otherwise lethal dose of live GBS (100 bacteria). Administration of the immunotoxic agents cyclophosphamide, carrageenan, or cobra venom factor during the immunization period and/or shortly before challenge significantly suppressed host resistance. For example, the composite mortality rate for unimmunized mice was 98% and the rate for immunized mice was 8.5%. For all groups treated with cyclophosphamide (one 75 mg/kg dose 48 h before each immunization) the mean mortality was 41 +/- 18%. The consistency of the model was evaluated by repetition of several treatments in independent experiments, and the model's consistency is comparable to that of other host resistance models.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444808 TI - Decrease of epinephrine-induced arrhythmia threshold in ethanol exposed rats. AB - An association between cardiac arrhythmias and ethanol use has been observed for some time. The sympathetic nervous system presumably plays an important role in the manifestation of cardiovascular ethanol responses. Therefore, we investigated the effects of ethanol treatment on epinephrine-induced arrhythmias. Female Wistar rats received 10 vol% ethanol or 2.5% glucose (control group) in their drinking water for 45 days. In ether anesthetized animals of both groups epinephrine (10 micrograms/kg.min) was infused via a lateral tail vein. The threshold dose for arrhythmias after epinephrine infusion (mainly 2nd and 3rd degree AV-blocks) was reduced beginning 2 days after the start of the ethanol treatment and the incidence of AV-blocks during epinephrine infusion was increased. During the ethanol treatment the prohypertensive epinephrine effect was slightly increased. The reflex bradycardia was not changed after repeated epinephrine infusion by ethanol treatment, whereas it was nearly abolished in the control group. No blood ethanol could be detected during the time of epinephrine infusion (9-12 a.m.), but determinations at 11 p.m. yielded a concentration of 0.13 +/- 0.02 mg/g. The results show that the epinephrine-induced bradyarrhythmia threshold is reduced and the frequency of arrhythmic events is augmented in rats exposed to ethanol in the drinking fluid. PMID- 1444809 TI - Cellular toxicity of toluene on mouse gamete cells and preimplantation embryos. AB - Toluene is an aromatic hydrocarbon, which has been used in the paint, lacquer and glue industry. It has been detected in municipal water supplies. Previous mouse in vivo studies indicated that toluene administrated by gavage increased the embryonic mortality. The present in vitro study demonstrated that a concentration of toluene higher than 8.67 micrograms/ml not only decreased sperm motility and inhibited fertilization, but also significantly increased preimplantation embryo degeneration. At lower levels no effects were observed and the adverse effect levels were approximately 780 fold higher than reported levels in municipal water supplies. PMID- 1444810 TI - Hair analysis for drugs of abuse. V. The facility in incorporation of cocaine into hair over its major metabolites, benzoylecgonine and ecgonine methyl ester. AB - We studied the incorporation of cocaine (COC), benzoylecgonine (BE) and ecgonine methyl ester (EME) into hair from blood. At first, the time courses of three drugs in rat plasma following i.p. administration of cocaine were investigated over 360 min. AUCs of COC, BE and EME in plasma were 14.2, 60.7 and 53.4 micrograms/ml/min, respectively. In contrast, the concentrations of the three compounds in hair were 16.4, 1.7 and 0.8 ng/mg. In spite of that, the AUC of COC in plasma was much lower than that of the other two compounds in plasma, the concentration of COC in hair was much higher than that of the other two compounds. The incorporation of COC into hair was much greater than that of BE and EME. If the incorporation of drugs from blood into hair is compared by [concentration in hair]/[AUC in plasma], that of COC, BE and EME is represented by 77:1.9:1. Our results suggest that the incorporation of drugs into hair from blood unexpectedly depends upon the physical properties of each drug. PMID- 1444811 TI - Statistical analysis of toxicokinetic data by nonlinear regression (example: inhalation pharmacokinetics of propylene) PMID- 1444812 TI - A national validation study of the acute-toxic-class method--an alternative to the LD50 test. AB - In a national collaborative study an alternative to the classical LD50 test--the acute-toxic-class method--was validated. With this testing procedure mortality ranges are determined between defined dose levels that are used for classification and labelling in the European Community. The results were compared with LD50 data obtained from the literature which were categorized according to the defined dose levels. The results of this collaborative study have shown that the acute-toxic-class method allows allocation to the toxicity classes of very toxic, toxic, harmful and unclassified in the same manner as on the basis of the classical LD50 tests. The acute-toxic-class method uses fewer animals and subjects fewer animals to pain and distress than the LD50 test and yields the same information on toxic signs in the treated animals. Identical classifications were obtained by the six participating laboratories in 86% of the tests. This demonstrates that the acute-toxic-class method results in excellent reproducibility in comparison to the classical LD50 test and that this new method is a reliable alternative to the LD50 test. PMID- 1444813 TI - Comparative toxicity of four chlorinated dibenzo-p-dioxins (CDDs) and their mixture. Part I: Acute toxicity and toxic equivalency factors (TEFs). AB - There is presently no scientifically proven method to assess the toxicity of environmental samples containing complex mixtures of chlorinated dibenzo-p dioxins (CDDs) of known composition. Their risk assessment is currently based on the interim concept of toxicity equivalency factors (TEFs), with the unproven assumption that all interactions of CDDs are additive. To address this problem we conducted acute toxicity studies with four different CDDs, viz 2,3,7,8 tetrachlorodibenzo-p-dioxin (tetra-CDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (penta-CDD), 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (hexa-CDD) and 1,2,3,4,6,7,8 heptachlorodibenzo-p-dioxin (hepta-CDD), all containing chlorine substituents in the crucial 2,3,7,8-positions. The homologues, dissolved in corn oil/acetone, were administered to groups of five male Sprague Dawley rats at several doses (at least three) by gastric intubation. The obtained mortality data were employed to calculate the LD20,50 and 80 for each homologue. These data were subsequently used to prepare equipotent doses (expected mortality of 20, 50 and 80%) of a mixture containing all four homologues, each of them contributing one fourth of the toxicity, under the assumption of additive toxicity. The obtained LD50 value and (TEF) was for tetra-CDD 43 micrograms/kg (1), penta-CDD 206 micrograms/kg (0.2) hexa-CDD 887 micrograms/kg (0.05) and hepta-CDD 6325 micrograms/kg (0.007), respectively. The dose-response to the mixture confirmed the hypothesis of strict additivity in the acute toxicity of the four CDD homologues. PMID- 1444814 TI - Spontaneous neoplasms in aged Sprague-Dawley rats. AB - Incidence of neoplastic lesions in untreated Sprague-Dawley rats (1340 males and 1329 females) used as controls in 17 carcinogenicity studies are tabulated and evaluated. In male rats, the most common neoplasms were benign pheochromocytomas and keratoacanthomas (4.0% in each case) followed by pancreatic islet cell adenomas (3.7%), thyroid parafollicular cell adenomas (3.6%), fibromas and squamous cell papillomas of the skin and hepatocellular adenomas (2.0% in each), malignant lymphoma lymphocytic (1.9%), histiocytic sarcomas (1.4%), and adrenal cortical adenomas (1.2%). In female rats, the most common neoplasms were of mammary gland origin (31.3%: fibroadenoma 19.0%, adenocarcinomas 8.8%, and adenomas 3.5%) followed by thyroid parafollicular cell adenomas (2.9%), uterine endometrial stromal polyps (2.6%), adrenal cortical adenomas (1.9%), malignant lymphoma lymphocytic (1.6%), fibromas in the skin (1.3%), and pancreatic islet cell adenoma (1.1%). Metastases were observed from pheochromocytomas, hepatocellular carcinomas, nephroblastomas, renal pelvis transitional cell carcinoma, interstitial cell tumor and seminoma of the testes, Zymbal's gland adenocarcinomas, and mammary adenocarcinomas. PMID- 1444815 TI - Poisoning with 2,4-dichlorophenoxyacetic acid treated by hemodialysis. AB - In this paper four patients are presented who had been poisoned by 2,4 dichlorophenoxyacetic acid (2,4-D). The first patient, aged 51 years, had attempted to commit suicide by taking orally 400 ml of a 40% solution of 2,4-D. He was admitted in a coma, 6.5 h after poisoning. Extracorporal hemodialysis was performed and the course of the illness was satisfactory. The second patient, aged 80 years, had accidentally drunk 100 ml of a 40% solution of 2,4-D. He was admitted in a coma a few hours after poisoning. Hemodialysis and resin hemoperfusion were performed and the course of the illness was satisfactory. Prior to the above therapy the patient had a 2,4-D serum concentration of 177 mg/100 ml. 2,4-D clearance was 56.3 ml/min during this therapy. The third patient, aged 24 years, had drunk 200 ml of a 40% solution of 2,4-D in a suicide attempt, and paraquat poisoning was also suspected. He was admitted 10 h after poisoning and immediately hemodialysis and hemoperfusion were carried out: the course of the illness was satisfactory. On admittance the concentration of 2,4-D in serum was 122.5 mg/100 ml, and clearance was 72.9 ml/min during treatment. The fourth patient, aged 50 years, had accidentally drunk 100-200 ml of a 40% solution of 2,4-D. He was admitted in a coma 3 h after poisoning. Hemodialysis was performed and the course of the illness was satisfactory. On admittance the concentration of 2,4-D in serum was 37 mg/100 ml and clearance was 68.7 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444817 TI - [A new counting method of airborne Japanese cedar (Cryptomeria japonica) pollen allergens by immunoblotting using anti-Cry j I monoclonal antibody]. AB - We produced monoclonal antibodies against the major allergen of Japanese cedar (Cryptomeria japonica) pollen, Cry j I. KW-S10 antibody reacted only with Japanese cedar pollen and KW-S91 antibody reacted to most angiospermae pollens as well as Japanese cedar pollen. Using these antibodies, we devised a new counting method of Japanese cedar pollen allergen particles by an immunoblotting technique. Airborne pollen allergens were collected on vaseline coated glass slides or Burkard's sampling tape and were transferred onto polyvinylidene difluoride (PVDF) membranes. The membranes were treated with anti-Cry j I monoclonal antibody conjugated with alkaline phosphatase. Pollen allergens were detected as spots on the membranes after staining with phosphatase substrate (BCIP/NBT). This method using KW-S10 antibody measured only the amounts of allergen from Japanese cedar pollen, while with KW-S91 antibody, the method measured the amounts of pollens which have antigenicity in common with Japanese cedar pollen. PMID- 1444816 TI - Kinetics and renal effects of formic acid in occupationally exposed farmers. AB - Twelve male farmers (38 +/- 14 years of age, mean +/- SD) were exposed to 7.3 +/- 2.2 mg formic acid/m3 for 8 h in the silage making (mean +/- SD, N = 12). Each gave urine samples immediately, 15 h and 30 h after the end of the exposure. The excretion of formate was linearly related to the exposure 15 and 30 h after the exposure. Exposure increased renal ammoniagenesis and urinary calcium at 30 h post-exposure. Both biochemical effects may be explained by the interaction of formic acid with the oxidative metabolism of renal tubular cells, as formic acid is a known inhibitor of the cytochrome oxidase. In view of these renal effects, the current hygienic limits may not entirely protect exposed individuals. PMID- 1444818 TI - [Study of liver function in babies with atopic dermatitis by using 13C-methacetin breath test]. AB - We measured serum GOT levels in babies with atopic dermatitis and food allergy. Two hundred and fourteen babies (133 male, 18 female, under 2 years of age) who first visited the Department of Allergy in the National Children's Hospital were examined. Their serum GOT levels were higher than normal; the younger they were, the higher the serum GOT levels were. We carried out the 13-methacetin breath test (MBT) on 11 babies with atopic dermatitis and high serum GOT levels as well as 5 normal babies to estimate their hepatic microsomal function. 13C-methacetin was administered (0.5 mg/kg) orally, and breath was collected at 30 minutes before and immediately before administration. After administration it was collected at 15 minute intervals for the first hour and 45 minute intervals for 90 consecutive minutes afterwards. The level of 13CO2 in their breath was determined with a mass spectrometer. The peak level of 13CO2 excretion (%dose/hr) in the atopic babies with high serum GOT levels was lower and the time required for 13CO2 excretion to reach its maximum level was longer than in normal babies. Also their 13CO2 clearance rate (%/hr) was lower. These results suggested that there was some relationship between atopic dermatitis and liver dysfunction in babies. PMID- 1444819 TI - [Efficacy of early use of continuous isoproterenol inhalation therapy for severe asthma attacks in children]. AB - The aim of this study was to evaluate the efficacy and safety of continuous isoproterenol inhalation therapy for asthma attacks in children. We used l-body isoproterenol (Proternol L) in 22 children with 32 episodes of severe attacks. One of them did not respond to this therapy, and two had complications (atelectasis and pneumothorax). Twenty-nine cases were divided into three subgroups according to their clinical scores; A) scores less than or equal to 4, which meant that they were in the early stage of severe attack (n = 9), B) scores 5-6, which meant impending respiratory failure (n = 17), C) scores greater than or equal to 7, which meant respiratory failure (n = 3). The values of SpO2 at the start of this therapy were 94.8, 91.5, 82.0%, respectively. The more severe their attacks were, the lower their SpO2 levels were. The periods until their scores became zero were 0.78, 6.3, 17.2 hours, respectively. There were significant differences between each period respectively (p less than 0.001, p less than 0.01). Heart rates decreased when their symptoms improved, and other adverse effects were not detected. These results suggest that this therapy is effective and safe for children with severe asthma attacks, especially in the early stage. PMID- 1444820 TI - [A study of skin test with regard to age differences and agreement with positive results from the RAST and ELISA methods]. AB - Skin tests of the scratch type were performed on 132 asthmatic patients with 28 allergens. The threshold titers of skin test, RAST and ELISA of house dust, HD mites, Japanese cedar pollen, ragweed pollen and orchard grass pollen were included. The main skin-positive allergens among the patients were as follows: house dust, HD mites, Japanese cedar pollen, orchard grass pollen, timothy grass pollen and ragweed pollen. There are age differences on skin-positive rates among 4 age groups of the patients; 90% of the patients under 40 years old groups reacted positively to any of 28 allergens, while half number of the patients groups over 40 years old reacted positively to the allergens. According to the quantitative analysis between threshold titers of skin test and RAST titers using house dust and HD mites allergens, specific IgE production shall be decreased in the patients over 40 years old. Using 5 main allergens above mentioned, the agreements of positive responses between three methods were compared. RAST positive responses correlated well with the skin test results, while ELISA positive responses correlated rather poorly with the skin test results. However, correlation between RAST and ELISA results was relatively good. The correlation of positive responses to house dust and HD mites by the three methods was very good, but there were some cases where positive responses were obtained by only one of the methods. PMID- 1444821 TI - [The dysfunction of human peripheral blood dendritic cells on concanavalin A induced T cell responses in patients with systemic lupus erythematosus]. AB - The accessory cell (AC) functions of peripheral blood dendritic cells (PDC) in concanavalin A (Con A)-induced T cell proliferation were investigated in patients with systemic lupus erythematosus (SLE). In Con A-induced T cell proliferation using added autologous PDC, AC activity was present in SLE patients (p less than 0.01). The Con A-induced T cell proliferation, however, was significantly lower in SLE patients than in normal subjects (p less than 0.01), and the level of decrease became greater with increased activity of the disease (p less than 0.01). In investigating the Con A-induced T cell proliferation using added allogeneic PDC, we compared T cells from SLE patients + PDC from normal subjects or T cells from normal subjects + PDC from SLE patients with T cells + allogeneic PDC both from normal subjects. The former two combinations showed significantly reduced T cell proliferation in active SLE (p less than 0.01 for each), while no significant differences were found for inactive SLE. The above results suggest that the reduced function of PDC as AC may be involved in reduced Con A-induced T cell proliferation in patients with active SLE. PMID- 1444822 TI - Is a trypsin-like protease of mites a Der f III allergen? AB - A trypsin-like protease was purified from mite (Dermatophagoides farinae) fecal extract. In SDS-PAGE, the mite trypsin-like protease showed a single band at 34 kD. The purified trypsin-like protease possessed potent allergenic activity. Both the twenty N-terminal amino acid sequence and the amino acid composition of the purified protease were very similar to those of Der f III. These data strongly suggest that the trypsin-like protease in the mite is a Der f III allergen. PMID- 1444823 TI - [Immunity, allergy and aging]. PMID- 1444824 TI - [The inhibitory effects of anti-asthmatic agents on ethanol-induced bronchoconstriction in Japanese asthmatic patients]. AB - Asthmatic symptoms are worsened after drinking small amounts of alcoholic beverages in Japanese asthmatic patients. Our previous results showed that the ingestion of pure ethanol caused a fall in FEV1.0 in about half of the Japanese asthmatics we studied. We studied the inhibitory effects of pretreatment with three kinds of anti-asthmatic agents on ethanol-induced bronchoconstriction in six Japanese asthmatic patients. We tested oral cyproheptadine hydrochloride (8 mg), which is an anti histamine agent, inhaled disodium cromoglycate (2 mg), which has an inhibitory effect on the release of chemical mediators from mast cells, and inhaled atropine sulfate (3 mg), which is an anti-cholinergic agent. Pretreatment with cyproheptadine significantly inhibited the fall in FEV1.0 120 minutes after ethanol challenge (p less than 0.05). Inhaled DSCG had significant inhibitory effects on the fall in FEV1.0 15 and 30 minutes after ethanol challenge (p less than 0.05). Inhaled atropine had no inhibitory effect. These results suggest that histamine, released from mast cells, plays an important role in ethanol induced bronchoconstriction in Japanese asthmatic patients. PMID- 1444825 TI - [Proposal of a new classification of adult bronchial asthma--child onset asthma, adult onset asthma and adult relapse asthma. Project Team for Research into Adult Bronchial Asthma in Japan]. AB - The first nationwide research into adult bronchial asthma in Japan proposed a new classification of adult asthma. Adult asthma was categorized into child onset asthma, adult onset asthma and adult relapse asthma. The frequency of child onset asthma, adult onset asthma and adult relapse asthma in adult asthma was 11.2%, 77.3% and 3.7%, respectively. The frequency of child onset asthma decreased markedly in the older age group. On the other hand, the frequency of adult onset asthma increased, and reached more than 90%, in the older age group. The frequency of the following factors: atopic asthma, complications with other atopic diseases, mild asthma, male patients, experience of mechanical ventilation, visits to night clinics and oxygen therapy on acute attack, was significantly higher in the child onset asthma group than in the adult onset asthma group. The frequency of infectious type, aspirin intolerance, steroid dependent asthma, severe asthma and regular medication was significantly higher in the adult onset asthma group. Adult relapse asthma seemed to fall between these two groups. Based on the above observations, we proposed a new classification of adult asthma which includes child onset asthma, adult onset asthma and adult relapse asthma. PMID- 1444826 TI - [Studies of lymphocyte activation on late asthmatic response in adult asthma]. AB - Late asthmatic response (LAR) as well as delayed asthmatic response (DeAR) is an important clinical characteristic in adult severe asthma. These responses might be based on cell to cell interaction following lymphocyte activation. Therefore, to clarify the pathogenesis of LAR, we studied the lymphocyte functions of adult asthmatics with LAR provoked by inhalation of house dust and Candida antigen. The results revealed that mite antigen-specific lymphocyte blastogenesis, IL-2 and ECF production were significantly higher in asthmatics with LAR provoked by house dust antigen than in normal subjects and asthmatics with IAR by house dust and LAR by Candida, though there was no significant difference in NCF. Candida antigen-specific lymphocyte blastogenesis, IL-2, ECF and NCF production were significantly higher in asthmatics with LAR provoked by Candida antigen than in normal subjects and asthmatics with IAR or LAR provoked by house dust. There was a positive correlation between Candida antigen-specific IL-2 and NCF production in asthmatics with LAR provoked by Candida antigen. These results suggest that antigen-specific lymphocyte activation may play an important role in the pathogenesis of LAR, especially in asthmatics with LAR provoked by Candida antigen, and that LAR and DeAR should be considered inclusively as cell-mediated allergy. PMID- 1444827 TI - [Diagnosis of food allergy based on rectal mucosal cytology]. AB - We performed rectal and/or oral challenge tests on 8 patients with suspected but unproven diagnosis of food allergy based on detailed medical history and findings from radioallergosorbent tests (RAST). The cells appearing in the rectal mucosal smear serially for 48 hours after allergen challenge were examined. The following results were obtained: 1) Significant numbers of not only eosinophils but also mast cells appeared in the rectal smears after challenges with suspected-food allergens, but not with unrelated foods. This confirmed the antigen-specificity of the method. 2) In some cases, the appearance of mast cells and eosinophils was bimodal, suggesting the existence of a later allergic response in addition to an immediate-type reaction. 3) The food-specific appearance of mast cells and eosinophils was observed in association with clinical symptoms after challenge, even in patients whose IgE antibodies to the allergen were negative or commercially unavailable. In conclusion, we propose that rectal mucosal cytology in conjunction with rectal and/or oral challenge tests is a reliable and objective method to diagnose unproven or suspected food allergy. PMID- 1444828 TI - [Evaluation of Oriton IgE, a new kit for measurement of allergen specific IgE antibodies]. AB - To determine whether Oriton IgE kit, a new kit for the measurement of allergen specific IgE antibodies, is useful in screening allergen-specific antibody, we measured the titers of IgE antibodies against 11 different allergens (house dust 2, Dermatophagoides farinae, Japanese cedar, ragweed pollen, egg white, milk, cat epithelium, dog epithelium, Candida, Alternaria and Aspergillus) with the Oriton IgE kit, and the results were compared to those of intradermal tests and RAST in 103 allergic patients and 10 normal subjects. There was a clear correlation between IgE antibody titers measured by the Oriton IgE kit and the RAST. The correlation coefficient was 0.76 (p less than 0.01) and the total correspondence rate was 85.9%. We also found strong correlation between the Oriton IgE kit and RAST in IgE antibody titer against 5 different allergens, Dermatophagoides farinae, Japanese cedar, ragweed pollen, egg white and Candida. The correlation coefficient was over 0.70. The correspondence rate, sensitivity and specificity of the Oriton IgE kit to intradermal tests was 71.8%, 45.3% and 87.8% respectively. The sensitivity of the Oriton IgE kit was slightly higher, while the specificity was slightly higher in RAST, although the differences were not statistically significant between these methods. Correspondence rate of the Oriton IgE kit was similar to that of RAST. These results suggested that the Oriton IgE kit is useful in screening allergen specific IgE antibodies. PMID- 1444829 TI - [Evaluation of the sensitized condition of patients with allergic diseases in Okinawa using the MAST allergy system]. AB - We determined, using the MAST system, specific IgE antibodies to allergens in the circulating blood of 127 patients with bronchial asthma, allergic rhinitis and atopic dermatitis in Okinawa. The positive rates to inhalant allergens in all patients examined by the MAST system were as follows: Dermatophagoides farinae 65%, house dust 58%, cat epithelium 17% and Japanese cedar 9%. In addition, the positive rates to food allergens found in all patients were as follows: wheat 16%, shrimp 14%, egg white, rice and crab 12%. The average number of positive allergens in the patients with atopic dermatitis was larger than that in those with allergic respiratory diseases only. The above five specific IgE antibodies were detected simultaneously in 12 (9%) of the 127 patients. In addition, the average number of overlapping positive allergens was 2.0 in all patients. From these results, it was suggested that the number of overlapping positive allergens in patients on Okinawa is smaller than in other areas of Japan as compared with other papers. PMID- 1444830 TI - [Time course of drug concentrations in nebulizers and nebulized solutions]. AB - The drug concentrations in nebulizers and nebulized solutions generated by the ultrasonic nebulizer OMRON NE-U10B and the jet nebulizer INSPIRON NEBULIZER 002305 were examined. With the ultrasonic nebulizer, increases in the concentrations of saline, DSCG and isoproterenol in the nebulizer were observed; the concentrations of those in the nebulized solutions also increased. The increase was most dramatic just before the solution was emptied. No degradations of DSCG or isoproterenol were detected in the nebulized solutions, indicating that these drugs are stable against ultrasonic nebulization. An increase in the drug concentrations in the jet nebulizer was also observed. The concentrations of the nebulized solutions also increased, but the concentrations in the nebulized solution were lower than those in the nebulizer at any time. On inhalation therapy, it is important to give consideration to these concentration changes. The nebulizer should not, for example, be refilled with a new drug solution. PMID- 1444831 TI - [Itching and allergic diseases]. PMID- 1444832 TI - [A rapid measuring technique for allergen-induced IL2 responsiveness of lymphocytes by the propidium iodide-staining method. Detection of the etiological antigen in patients with allergic diseases]. AB - A method for rapidly measuring the interleukin 2 (IL-2)-responsiveness of allergen-stimulated lymphocytes has been newly developed using propidium iodide (PI) staining and drawing ink quenching of the fluid medium fluorescence. There was a linear correlation between the number of PI-stained cells and the fluorescence intensity. The background was less than 5 percent. This fluorochromasia assay reflected the cell number for the quantitative measurement of lymphocyte proliferation. Antigen-activated patient cells added to IL2, showed greater increase in 3H-TdR uptake than IL-2-untreated cells, and were capable of acquiring IL2 responsiveness. Increased numbers of the cells were observed by both the PI- and trypan blue-staining methods. In contrast, unstimulated cells also showed increased 3H-TdR uptake response without increased cell numbers on stimulation with r-IL2 by a 6.8 to 19.3 fold stimulation index compared to the antigen-activated cells. The results indicated that the unstimulated cells in addition with r-IL2 still remained in the initial phase of the DNA-synthetic (S) period through the cell cycle, whereas the activated cells had passed through the post-synthetic gap (C2) and/or cell division at mitosis (M). 3H-TdR uptake of cultured cells usually demonstrates the presence of antigen-sensitized lymphocytes by in vitro proliferative response, and shows an increased stimulation index in 4 or 7 day cultured cells on stimulation with allergens. However, proliferation of some cell populations decreased; furthermore no distinct differences in cell proliferation between allergic and normal lymphocytes were observed, as is usual in this assay, although the present method was capable of measuring increased-IL2 responsiveness of patient lymphocytes. The results indicate that the 3H-TdR uptake method can not be substituted for cell enumeration in the evaluation of the antigen-specificity of induced-IL2 responsiveness of activated cells. Therefore, cell enumeration using the PI staining method may be preferable in this system. The induced response was observed in lymphocytes from patients with atopic dermatitis, bronchial asthma and/or allergic rhinitis specifically on stimulation with the antigen causing clinical symptoms. The results obtained using the PI-staining method were very similar to those in previous reports where the trypan blue staining method was employed. The present method appears to be capable of rapidly screening etiological antigens for disease and easily monitoring clinical activity. PMID- 1444833 TI - [Inhibition of Cls activity by methylprednisolone]. AB - From a clinical study it was found that serum ClINH activity increased 6 hours after methylprednisolone (MP) pulse therapy in all the patients we studied with connective tissue diseases. Furthermore plasma ClINH-Cls complex decreased after pulse therapy. These phenomena lead us to investigate the effect of MP on Cls. 1) When a constant amount of Cls (8 micrograms/ml) was incubated with several concentrations of MP (2-50 mg/ml), the Cls activity of consuming C4 hemolysis was inhibited by MP in a dose-dependent manner. 2) MP inhibited consumption of C2 as well as C4 by Cls in a dose-dependent manner, even when MP had been removed by dialysis following incubation with Cls. These experimental data suggested that the trace amounts of Cls generated by immune complexes could be inhibited by long circulation of MP even at low concentrations in vivo, and resulted in a decrease of ClINH consumption and ClINH-Cls complex formation. These results indicated that the inhibition of Cls activity is one of the most important mechanisms in the process of the anti-inflammatory effect of MP in vivo. PMID- 1444834 TI - [A relationship between the annual onset day of Japanese cedar pollinosis and pollen dispersion]. AB - A statistical analysis of the annual day of onset of Japanese cedar pollinosis was carried out on a total of 305 patients seen at the out-patient clinic for allergic diseases in the Department of Otorhinolaryngology of Kyoto Prefectural University of Medicine between 1989 and 1991 (3 years). The day of onset varied among individuals and was distributed over a period of about one month, in patient number statistics, however, a clear single peak was seen for all 3 years. The day of onset in most patients showed tendency to peak after January 1, i.e., when the maximum temperature integral is approximately 450 degrees C, on warm days where the maximum temperature exceeds 15 degrees C, on days where there is little rain, and on days when there is a strong southerly wind. This peak onset day is about 3 weeks after first day of pollen count, or 3 or 4 days before the first dispersion peak, which corresponds to the day on which pollen dispersion begins in earnest. Furthermore, it was found that there was a drastic increase in the attack rate (from 10% to more than 50%) in pollinosis patients about 1 week before the peak day of onset. By the first dispersion peak, 70-80% of the patients had experienced an attack. The results of the present study may be useful in pollen forecasting and in treating early pollinosis in the dispersion season. PMID- 1444835 TI - [Allergy to casein hydrolysate formula. A study of sensitizing allergen]. AB - A six-month old baby, who had been fed for 2 months with casein hydrolysate formula (MA-1) for treatment of milk allergy, developed diarrhea. The baby's RAST score for milk was negative. IgE antibodies to MA-1 but not to MA-1 depleted of lipid (fat-free MA-1), were demonstrated by enzyme-linked immunosorbent assay (ELISA). It was confirmed by the appearance of numerous mast cells and eosinophils in a rectal smear taken after challenge with MA-1 (but not detected after challenge with fat-free MA-1) that some component in the lipid of MA-1 must be an allergen in this patient. PMID- 1444836 TI - [A case of food-dependent anaphylaxis induced by alcohol]. AB - A 35-year-old male doctor experienced an anaphylactic reaction of urticaria, unconsciousness and hypotension one hour after taking a meal including crab meat and alcohol (beer 350 ml+Japanese sake 100 ml). He recovered within several hours after emergency treatment. Another attack occurred 6 months later after taking a meal including crab meat and alcohol. Serum IgE showed 3073 IU/ml. IgE-RAST and skin tests were positive for crab. A crab meat plus alcohol challenge test revealed a slight increase in plasma histamine level. This is a rare case of food (crab meat)-dependent anaphylaxis possibly induced by alcohol. PMID- 1444837 TI - [Role of opioid peptide in rheumatoid arthritis--detection of beta-endorphin in synovial tissue]. AB - The presence of beta-endorphin (beta-end) was immunohistologically identified in synovial tissue samples biopsied from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The amount of beta-end in culture supernatants of synovial tissue explants was also determined by RIA. beta-end was strongly detected in mainly superficial synovial cells, vascular endothelial cells and a few synovial interstitial cells in RA patients, but not in OA patients. In RA patients the beta-end concentration was significantly higher in the supernatants of tissue explants (26.4 +/- 8.3 pg/ml) than in the plasma of the same patients (15.3 +/- 2.5 pg/ml) (p < 0.01). Using isolated synovial cells, the beta-end concentration in the culture supernatants of non-adherent cells (19.4 pg/ml) was higher than that of adherent cells (4.0 pg/ml). It is suggested that beta-end is produced by non-adherent cells such as lymphocytes and neutrophils in addition to synovial lining cells and endothelial cells and may play some role in the pathology of RA synovial inflammation. PMID- 1444838 TI - Proteoglycan obtained from bovine aorta suppress thrombin-induced platelet aggregation. AB - Proteoglycan (PG), isolated and purified from bovine aorta (intima-media), consisted of 68.6% chondroitin 4/6-sulfate (CS 4/6-S), 30% dermatan sulfate (DS), 1.4% heparan sulfate (HS), and a trace of hyaluronic acid (HA). PG did not affect platelet aggregation induced by ADP, collagen, and epinephrine, but inhibited that induced by thrombin. Of the standard GAGs investigated, hyaluronic acid (HA) and CS-4/6-S slightly inhibited only thrombin-induced platelet aggregation. However, PG and standard GAGs did not affect the thrombin induced aggregation of washed platelets. The effect of PG after papain digestion on thrombin-induced platelet aggregation was less potent than that before. It is suggested by the results of this study that PG in the aorta inactivates plasma thrombin, probably by inhibiting thrombin activators or potentiating substances which inactivate thrombin and that these effect of PG would be mainly due to PG-DS and partly due to PG-HS. PMID- 1444839 TI - Metabolic aspects of endothelial cells cultured from rat aortae. AB - We measured the lactate production, oxygen uptake and ATP in aortic endothelial cells cultured from young Wistar female rats. For these experiments, thoracic aortae were removed from the animals, minced into small pieces and transferred onto culture plates, to which a growth factor was added. When the endothelial cells had proliferated, the original pieces were removed from the culture and the remaining cells were subcultured until the 3rd passage. Regarding the growth curves of the 3rd passage, a logarithmic growth phase (Pg) was found from the 2nd to the 7th days and a stationary phase (Ps) followed thereafter. The ATP levels in the Pg and Ps were unchanged. Rates of lactate production and oxygen uptake were higher in the Pg than in the Ps. Only in the Ps was an interrelationship between these estimations found, suggesting that the confluent state exhibits metabolic cooperation between the cells in culture. PMID- 1444840 TI - Parenteral lipid emulsion-induced atherosclerosis in the obese Zucker rat and its lean littermate. AB - We have shown previously that parenterally-administered lipid emulsions can be utilized to induce early atherosclerosis in the aortas of Sprague-Dawley rats. In order to evaluate the effect of obesity on lipid-induced atherogenesis, we have utilized this same approach in the present study to demonstrate that i.v. infusions of the parenteral lipid emulsion, Lipofundin-S, will induce in the genetically obese Zucker rat and its lean littermate aortic endothelial and myofibroelastic changes indicative of early atherogenesis. Four groups of rats were used: 1) obese controls, 2) obese lipid-infused, 3) lean littermate controls, and 4) lean littermate lipid-infused. Observations were made with light and transmission electron microscopy (TEM), using qualitative morphological criteria to evaluate the results. Based on the fact that both untreated control and Lipofundin-S-induced atherosclerosis was more frequent and generally more advanced in the obese animals than in their respective lean counterparts, it appears that the obese Zucker rat is more susceptible to both spontaneous and hyperlipidemia-induced atherosclerosis than its respective lean littermate. Thus, obesity in these animals, as might be the case in humans, could potentiate an atherogenic process already enhanced by hyperlipidemia. PMID- 1444841 TI - [Monoclonal antibodies to neuron-specific enolase in phenotyping lung cancer]. AB - Morphological assessment of two samples of monoclonal antibodies (mcAB) to gamma unit of neurospecific human enolase (NSE) is performed. It is established that mcABs interact in the tissue sections with neurons of the brain and spinal cord, gangliocytes of the central and peripheral nervous system this proving their specificity. 56 cases of lung carcinoma are studied using these mcABs; endocrine carcinoma was found in 11 cases, nonendocrine--in 45 cases. Neuroendocrine differentiation is revealed in 8 of 45 cases of non-small cell carcinoma; in all observations of small cell carcinoma NSE was found. PMID- 1444842 TI - [Morphologic characteristics of microadenomas of the large intestine]. AB - Tissue and cellular atypia, changes of the mucus chemical composition, protein secreting function, ATPase activity, differentiation of the epithelial cells and DNA replication with the widening of proliferation zone were registered morphologically in colon microadenomas. A pronounced increase of labelled small lymphocytes capable of proliferation is observed in the stroma. Fibrocytes are practically absent, fibroblasts are represented by young 3H-labelled forms. All these changes are considered as dysplastic. PMID- 1444843 TI - [Pathomorphologic verification of the prenatal diagnosis of developmental defects in trimester II fetuses]. AB - 153 foetuses were studied obtained after the artificial abortion for genetical indications. The scheme of the material investigation is given. Isolated, systemic and multiple defects were found in 39.0, 12.1 and 48.9%, respectively, and the contribution of the syndrome forms in the multiple developmental disturbances was 60.9%. The interruption of the pregnancy in 2% of cases was assessed as unfounded: as a consequence of hyperdiagnosis and in cases of treatable defects. The frequency of the discrepancy between prenatal and pathology diagnoses was 31.8% including hyperdiagnosis of the defect (1.3%), nosological disagreement (13.3%), the lack of diagnosis of the additional defects detectable during II trimester by present ultrasound methods (17.2%). The efficacy of the work of the prenatal diagnostic centre is, according to the authors, the number of justified interruptions of pregnancy (98% in this study). PMID- 1444844 TI - [Metastasizing chondroblastoma of the trachea]. PMID- 1444845 TI - [Results of the discussion of diagnosis]. PMID- 1444846 TI - [From the teacher's letters (30 years since the death of Sh. I. Krinitskii)]. PMID- 1444847 TI - [Autoimmunization and autoimmune diseases]. AB - Autoimmunization is understood as a type of immune reactions to the unchanged autoantigens only. Autoimmune processes can be subdivided into the physiological ("sanitary" and regulatory) and pathological ones. Physiological processes are of importance in supporting natural immunological tolerance while pathological processes develop on the basis of the physiological ones in presence of various defects of suppressive mechanisms of the immune system. Pathological processes are the basis of the autoimmune diseases and diseases with secondary autoimmune disturbances. The distinction between organo-specific and organo-nonspecific autoimmune diseases can be taken as their preliminary tentative classification. PMID- 1444848 TI - [Epidemiology and prevention of major cardiovascular diseases]. AB - Analysis of the situation in the Russian Federation indicates that despite a small downward tendency, cardiovascular diseases (CVD) remain a leading cause of death among the population. Epidemiology studies of major CVD risk factors detected their high prevalence in several cities of the Republic despite noticeable geographic differences. The claim that prevention of CVD should be started from childhood remains still declarative and needs further large comprehensive studies. The accomplished research prevention programmes turned out to be feasible at community level and allowed one to develop organizational forms of their realization. To bring these projects into everyday life is a challenge as it involves many social problems. PMID- 1444849 TI - [Ultrastructure of pulmonary squamous cell carcinoma as a prognostic factor in surgical treatment]. AB - 163 operated on patients were divided into 2 groups: the 1st group--those surviving 5 years without recurrence (44.2%) and the 2nd group--those dying earlier from the tumour progression (55.8%). Central carcinoma was in 104, peripheral one in 59 cases. The number of dark cells (DC) and the degree of desmosome development revealed ultrastructurally have the greatest practical importance as the favourable course in the 1st group was associated with the absence or low number of DC (7%) and the high number of desmosomes (89%). These indices were found in the 2nd group in 86 and 41%, respectively. Both indices are of independent importance and are not associated with the spread of the carcinoma. The level of DC is of greater importance. Prognosis of the squamous cell carcinoma is the worse the higher is DC number in the tumour and the lower the desmosome number. PMID- 1444850 TI - [Clinical morphology of chronic myeloid leukemia]. AB - The morphological features of chronic myeloid leukemia at different stages of the disease were specified basing on the study of bone marrow punch biopsies of 239 patients, surgically removed spleens of 32 patients, marginal liver biopsies of 22 patients and 69 autopsies. It was found valid to distinguish two histological variants: granulocytic and granulocytic-megakaryocytic. It was shown that in the latter form of leukemia myelofibrosis, primarily of reticulin type, often tends to develop. The granulocytic-megakaryocytic variant and the diffuse myelofibrosis were found to be related to the morphological manifestations of unfavourable prognosis of chronic myeloid leukemia. The accumulation of blast cells in the central parts of bone marrow cavities, as revealed in the punch biopsies is the indication of the beginning of the blast transformation. PMID- 1444851 TI - [Immunopathologic study of the myocardium in dilated cardiomyopathy]. AB - Myocardial tissues of patients with dilated cardiomyopathy were studied by immunofluorescence. While immunoglobulin A fixation was observed in myocardial capillary wall and cardiomyocyte sarcolemma in the majority of patients (11 of 12), immunoglobulin G and C3 complement component were a rare finding. In the vessel wall of heart allografts immunoglobulin A fixation occurred 3-6 days after transplantation. As a result of the intensive immunosuppressive therapy which was used after the operation immunoglobulin A disappeared from heart allografts within 4-5 weeks. Immunoglobulin A fixation in the heart of patients with dilated cardiomyopathy is attributed to the anti-tissue or antivirus antibodies and probably is involved in the development of this disease. PMID- 1444852 TI - [Changes in the human uterine vascular bed in myoma]. AB - With scanning and transmission electron microscopy characteristic changes in the endothelial lining of myometrial vessels of uterus affected with myoma were revealed. In the presence of longitudinally oriented folds and microgrowths on the luminal surface in a healthy myometrial part, a number of changes were observed in the myoma vessels. These included the disappearance of cell surface derivatives, disturbance of tight junction of endothelial cells borders, the rise of cells over the endothelial monolayer and formation of crateriform pits. The partition of the endothelial cells on myoma vessels was accompanied by the disturbance of the microvesicular transendothelial transport. PMID- 1444853 TI - [Computer program for the analysis of clinical diagnostic errors based on a pathology database]. AB - The program is tested on the material of 882 autopsy protocols. All parts of clinical and pathology diagnoses were included into the generation of the data base. Automatized analysis allowed to assess main characteristics of the patient material with a histogram demonstration of group statistics according to all positions considered as well as to obtain information on the influence of more complex pathology diagnosis of a main disease, sex and age on the frequency of clinical diagnosis mistakes. PMID- 1444854 TI - [Cystinosis in an adult]. AB - The paper reports a case of cystinosis with the involvement of kidneys, myocardium and liver in a female of 43. Late development of kidney failure might be due to a partial deficiency of the enzyme responsible for a cystine transport in the cell. PMID- 1444855 TI - [Role of iatrogeny in pathologic diagnosis]. PMID- 1444856 TI - [Re-examination of diagnosis formulation, assessment of clinical diagnosis quality and pathology documentation]. PMID- 1444857 TI - [Designation of giant mononuclear cells in tuberculosis]. PMID- 1444858 TI - [Proteins associated with nucleolar organizer regions: practical application in tumor histopathology and relationship to biological properties of the tumor]. AB - The argyrophilic staining of nucleolar organizer regions (AgNOR) has been found to be of increasing use in routine and experimental histopathology in the study of certain neoplastic lesions. The AgNOR reaction demonstrates the presence of argyrophilic non-histone proteins within NORs. The number of detectable NORs depends on several factors: the level of transcriptional activity, the number of NOR-bearing chromosomes in the karyotype, and the stage of the cell cycle in which they are sought. In man, five chromosomes have NORs, and these areas are the sites which hybridize with rRNA and are of importance with respect to the ultimate synthesis of protein. The results of AgNORs might be more informative if this technique would be applied simultaneously in cytological and histological specimens for each patient. It may also be important to examine the AgNORs profiles in stromal cells. PMID- 1444859 TI - [Incidence of malignant tumors in Russia and their prevention]. AB - Cancer incidence statistics in the Russian Federation and the evidence from epidemiological and experimental studies suggest that the priority in primary prevention of cancer should be given to smoking control. Discontinuation of smoking may prevent in Russia annually about 80,000 cases of cancer, or about 25% of all newly diagnosed cases of cancer in 1989 (excluding skin squamous and basal cell carcinoma). Another very important direction of cancer prevention in Russia is modification of diet in favour of increased consumption of fresh fruit and vegetables. The elimination of occupational carcinogens or a decrease in exposure to them would result in an important decrease in the incidence of certain cancers in highly industrialized areas. A decrease in the exposure to carcinogens in ambient air and the protection from exposure to ionizing radiation are of some, although limited, importance in cancer prevention. PMID- 1444860 TI - [Anatomical limitations for the performance of angioplasty in coronary multivessel disease]. AB - PURPOSE: To study anatomical limitation of coronary angioplasty, as alternative therapy in patients with multivessel disease and submitted to bypass surgery. METHODS: In 380 patients with multivessel disease and submitted to previous coronary bypass surgery, age ranged from 41 to 72 (average = 51) years, being 68% males. The following parameters were analyzed in the coronary arteriographies: anatomic aspects of the coronary arteries and distribution of the atherosclerotic stenosis. The patients were arranged in accordance to the criteria: complete revascularization, incomplete and no indication for coronary angioplasty. RESULTS: The patients were arranged in 3 different groups: I-80 (21%) patients included those in whom complete revascularization would be possible; II--55 (14.5%) patients in whom only incomplete revascularization but satisfactory would be possible and III--245 (65.5%) those patients in whom coronary angioplasty would no have indication. The data referind the patients of groups I and II were analyzed together--135 (35.5%) and arranged according to the number of arteries involved. It was observed: two vessel disease--71.8%, three vessel--18.6% and 4 or more vessel--9.6%. In group III it was observed 51.0% of the patients with 3 or more vessel disease. The major factors to contra indicate coronary angioplasty in group III included: chronic coronary obstruction 99 (40.4%); diffuse disease 11 (4.5%); technical difficulties 10 (4.1%); left main coronary artery obstruction 5 (2%) or when two or more causes were combined 120 (49%). CONCLUSIONS: Patients with multivessel disease and classic indication for coronary bypass surgery, have a basic limitation for angioplasty due to several anatomic factors. However, coronary angioplasty could be beneficial for a selected group of patients (35.5%) whenever a complete or incomplete revascularization could be obtained. PMID- 1444861 TI - [Electrocardiographic changes in accidental hypothermia]. AB - PURPOSE: Electrocardiographic alterations were evaluated in a group of accidental hypothermia patients, and correlated with values of core temperature, pH and plasmatic concentrations of Na+, K+ and Cl-. METHODS: Conventional 12-lead surface electrocardiograms were obtained in a group of 32 patients with accidental hypothermia after involuntary cold exposure. Cardiac arrhythmias, QRS configuration, ST-T segment and T wave alterations were analyzed. pH, Na+, K+ and Cl- serum concentrations were simultaneously measured. Electrocardiogram and electrolyte abnormalities were then correlated with the core temperature. RESULTS: Twenty-eight patients had abnormal electrocardiogram (90.6%). Sinus bradycardia and idioventricular rhythm were observed in 11 and 3 patients respectively. QT interval enlargement was found in 24 patients and Osborn wave in 28 cases. Altered T waves expressing an abnormal repolarization were observed in 23 cases. A significant negative correlation was obtained when J wave amplitude was correlated with core temperature levels. CONCLUSION: Hypothermia produces electrocardiographic abnormalities characterized by Osborn waves. Other minor findings include sinus bradycardia, idioventricular rhythm and long QT intervals. PMID- 1444862 TI - [Permanent heart valve prosthesis: half a century of search]. PMID- 1444863 TI - [Occlusion of patent ductus using the Rashkind system. Initial experience]. AB - Three patients were submitted to the Rashkind device technique for closure of a patent ductus arteriosus. The percutaneous transvenous technique was employed in every cases. A 12 mm prosthesis was utilized in one case and 17 mm prostheses in the other two cases. In the first case, after temporary occlusion of the ductus arteriosus, the prostheses was removed due to the technical impossibility of evaluation of the proximal umbrella position. In the second and third cases, the prostheses were duly liberated in the proper position, thus occluding the defects. This technique does not require general anesthesia, is indicated in patients over 6 kgs of body weight, and is a therapeutic alternative to the habitual surgical procedure. PMID- 1444864 TI - [Dissection in an adult with dilatation of the ascendent aorta diagnosed in childhood]. AB - Dilatation of the ascending aorta is relatively infrequent during childhood. Besides the Marfan syndrome, the congenital origin should be considered. We report a patient with dilatation of the ascending aorta diagnosed at the age of 10 who presented acute aortic dissection and rupture after a 13-year period of follow-up. Several aspects of the proper diagnosis are discussed. PMID- 1444865 TI - [Malignant schwannoma metastasizing to the heart]. AB - We introduce the case of a 34-year-old male with a malignant metastasizing tumor in the heart associated with skin manifestations. The patient was submitted to heart surgery to resect the tumor. The correct diagnosis was done by pathological findings and immunohistochemical methods and showed, malignant schwannoma. PMID- 1444866 TI - [Fracture of endocardial electrode at the tricuspid valve level]. AB - Female, 72 years old, had a permanent pacemaker system with endocardial pacing lead, and developed fracture of electrode at the point of passage across the tricuspid valve with episodes of asystole. PMID- 1444867 TI - [Kawasaki disease in Pernambuco, Brazil. Considerations on a case seen in a general hospital]. AB - The first case of Kawasaki disease in Pernambuco, Brazil, is described. An 18 month-old by presenting with fever, adenomegaly and mucocutaneous rash, had right and left coronary arteries dilation and aneurysm detected on echocardiography. Treated with a high dosage of aspirin, the patient is asymptomatic after a 7 month follow-up, with regression of coronary lesions. PMID- 1444868 TI - [A 22-year-old pregnant woman with respiratory deficiency of 10-day duration]. PMID- 1444869 TI - [Mapping with Technetium-99 methoxy-isobutyl isonitrile at the bedside after coronary thrombolysis]. AB - PURPOSE: To evaluate the feasibility of bedside Technetium99-methoxy-isobutyl isonitrile (99mTc-MIBI) cardiac imaging to assess perfusion after thrombolytic therapy (TT) for myocardial infarction (MI). METHODS: We studied 9 patients (mean age 59 +/- 9 years) submitted to TT with 100 mg of rt-PA in 90 minutes within the 6 hours of the onset of MI with subsequent angiography. 99mTc-MIBI was injected intravenously in a doses of 740 MBq immediately before TT start. Imaging was performed in three moments: study 1--as soon as the TT finished, study 2--3-18 hours after TT; study 3--7-10 days after TT. A perfusion score was established in each study and then compared to determine the perfusion patterns after TT. We compared through linear regression, the perfusion score with left ventricle ejection fraction, and with CKMB enzymatic peak. RESULTS: All patients had a patent infarct related artery. The perfusion score of study 1 varied from 12 to 22, mean 15.8 +/- 3.7, and correlated with ejection fraction (r = 0.9, p < 0.01) and peak CKMB (r = 0.78, p = 0.03). Four (44%) patients presented perfusion score improvement in study 2 (varied from 12 to 23, mean 16.8 +/- 4.3) and 8 (88%) in study 3 (varied from 12 to 28, mean 19.0 +/- 4.3). CONCLUSION: Bedside 99mTc-MIBI cardiac imaging is useful to quantify myocardial area under risk before TT, and to identify the late (7 to 10 days) benefit of TT. PMID- 1444870 TI - [Coronary insufficiency and heparin]. PMID- 1444871 TI - [Isradipine: a Brazilian multicenter study for the evaluation of the efficacy and safety in the treatment of mild and moderate arterial hypertension]. AB - PURPOSE: To evaluate the efficacy and tolerability of isradipine, a new dihydropyridine calcium antagonist, in the treatment of mild-to-moderate hypertension. PATIENTS AND METHODS: One hundred and eighty outpatients with different races, who had supine and orthostatic diastolic blood pressure (DBP) > or = 95 mmHg and < or = 115 mmHg, with a mean age of 52.03 +/- 11.47 years, 70 men, 110 women; underwent the study. After a two-week wash-out period patients received isradipine 2.5 mg b.i.d. for 90 days. Follow-up visits were performed at the 30th, 60th and 90th days of treatment. RESULTS: At the end of treatment (90 days), a statistically significant decrease (p < 0.05) in SBP and DBP in supine position was observed. A mean SBP was reduced from 159.28 +/- 16.99 to 142.51 +/- 15.12, and mean DBP declined from 101.49 +/- 6.82 to 86.63 +/- 7.40. Heart rate, weight, electrocardiograms and laboratory tests did not shows significant changes during treatment when compared to baseline evaluation. The most frequent related side effects (headache and dizziness with nausea) were transient, and at the end of the study 96.7% of the patients did not have any complaint. However, two patients were withdrawn from the trial because of important headache. CONCLUSION: Isradipine 2.5 mg by oral route, b.i.d. has shown to be effective and well tolerated in the treatment of mild-to-moderate hypertension in patients of both sexes and several ages and races. PMID- 1444873 TI - [Non-ischemic electrocardiographic changes]. PMID- 1444872 TI - [Unstable angina: comparison of the effects of diltiazem and propranolol]. AB - PURPOSE: To evaluate the effects of diltiazem and propranolol in patients with unstable angina. METHODS: Fifty-six patients with unstable angina, mean age of 55.4 +/- 8.5, 41 men and 15 women, were evaluated in a randomized, double-blind study of two groups of patients treated with diltiazem or propranolol at total daily doses of 180 mg and 120 mg respectively during the first 48 hours. After that the total daily doses was adjusted to 240 mg and 160 mg, respectively, until the 7th day. The first 48 hours, four times daily, clinical evaluation, CKMB data, ECG were obtained and two times daily until 7th day. A coronary arteriography was done on study entry. RESULTS: A significative reduction of angina crisis number, duration, intensity and the number of sublingual nitrates doses were observed equally in both groups. The SAP, DAP, HR and RR did not show statistical differences between groups. Individual groups analysis showed significative reductions of SAP, DAP and HR in propranolol group. The CKMB data, ECG alterations and coronary arteriography characteristics were similar. CONCLUSION: Both drugs were effective for the unstable angina treatment. PMID- 1444874 TI - Cardiovascular investigation in elderly patients with transient unresponsiveness. PMID- 1444875 TI - Human T lymphotropic virus type I-associated myelopathy. A report of 10 patients born in the United States. AB - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) (tropical spastic paraparesis/HAM) has rarely been reported in the United States. We present 10 well-documented cases with positive Western immunoblot test results and polymerase chain reactions for HTLV-I. The clinical and laboratory features of these American-born patients resemble those previously reported series of tropical spastic paraparesis and HAM from the Caribbean and Japan, but important differences were observed. In our study there were equal numbers of whites and blacks and of men and women. Age at onset was younger than that reported from the Caribbean and Japan. Rate of progression to paraparesis varied but was more rapid than previously reported. Half were transfusion recipients but six had multiple sexual partners, with one regularly interacting with prostitutes and reporting a history of drug abuse. Although more rapid progression was seen in the transfusion recipients, this did not explain the earlier age of onset in this group of patients. The HTLV-I, and the associated myelopathy, are endemic in Florida, suggesting that immigration from, and proximity, to the Caribbean basin are contributing risk factors. PMID- 1444876 TI - Reduction of the substantia nigra width and motor decline in aging and Parkinson's disease. AB - We studied the functional significance of the involutional and degenerative changes in the substantia nigra as seen on magnetic resonance imaging. The width of the pars compacta correlated with motor performance in both healthy elderly subjects and idiopathic Parkinson's disease groups. Patients exhibited significant reduction of the width of the pars compacta and the level of this reduction correlated strongly with the clinical status evaluated by the Unified Parkinson's Disease Rating Scale. These results suggest that pars compacta shrinkage may account for a substantial part of the structural substratum of motor decline in the elderly. Moreover, an analysis of the relationship of the midbrain damage with specific symptoms in Parkinson's disease could contribute to a better understanding of the pathogenesis of this degenerative process. PMID- 1444877 TI - Effect of long-term therapy on the pharmacodynamics of levodopa. Relation to on off phenomenon. AB - To determine how the response to levodopa is altered by long-term therapy, we examined the dose response to 2-hour infusions of levodopa in three groups of parkinsonian patients: those who were previously untreated, those who exhibited stable responses, and those who exhibited fluctuating responses to levodopa therapy, using tapping speed as an index of bradykinesia. The baseline tapping speed was greater in the patients with stable responses than in the untreated patients, probably representing a "long-duration response" to levodopa therapy. A "short-duration response," indicated by an increase in tapping speed lasting hours, was observed in most patients in all groups. The onset of the short duration effect was more rapid and the incremental increase in tapping speed was twice as large in the patients with fluctuating responses compared with the untreated patients and patients with stable responses. The duration of the short duration effect was greatest in the untreated group but did not differ between the groups with stable and fluctuating responses. Dyskinesia was not observed in any of the de novo patients but was observed in three of 12 patients with stable responses and eight of nine patients with fluctuating responses to levodopa therapy. Dyskinesia appeared before or with the antiparkinsonian effects in patients with stable responses, giving no indication of a higher threshold for dyskinesia in these patients compared with those with fluctuating responses. The plasma half-life clearance, volume of distribution, and maximum plasma concentrations of levodopa did not differ among groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444878 TI - Apomorphine test for dopaminergic responsiveness in patients with previously untreated Parkinson's disease. AB - We prospectively examined the predictive value of the apomorphine test for the therapeutic efficacy of sustained oral levodopa treatment in 62 patients with de novo Parkinson syndrome (no additional neurological deficit) who had not previously been treated with dopaminergic medication. Patients received 2 to 5 mg of apomorphine hydrochloride subcutaneously and a subsequent trial of oral levodopa of at least 3 months' duration. In three patients, response to apomorphine could not be evaluated owing to side effects experienced during the test. In the remaining 59 patients, the best predictor of response to oral levodopa was the apomorphine-induced relative decrease in the scores on the motor examination part of the Unified Parkinson Disease Rating Scale (UPDRS). At a cutoff value of 20% improvement in UPDRS scores, the test predicted the response to levodopa correctly in 50 patients (85%). The sensitivity of the test was 90%, specificity 88%. The positive predictive value was 95%. However, seven of 19 apomorphine test-negative patients experienced a good (n = 4) or partial (n = 3) improvement with levodopa therapy. Thus, the negative predictive value was only 63%. We conclude that response to apomorphine has a high predictive value for response to sustained oral levodopa treatment in most previously untreated patients, but a negative test should not preclude an adequate trial of oral levodopa. PMID- 1444879 TI - Treatment trial of oxiracetam in Alzheimer's disease. AB - Twenty-four carefully assessed patients with probable Alzheimer's disease were enrolled in a double-blind, placebo-controlled treatment study of oxiracetam, a nootropic agent reported to improve memory performance in patients with dementia. A broad battery of neuropsychological tests failed to reveal any improvement in the treated group or in any treated patient when individual test scores were analyzed. These findings indicate that oxiracetam is ineffective in reducing cognitive impairment due to Alzheimer's disease. PMID- 1444880 TI - Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. AB - Acetyl levocarnitine hydrochloride has been reported to retard dementia in patients with Alzheimer's disease. In a double-blind, parallel design, placebo controlled pilot study of 30 mild to moderately demented patients with probable Alzheimer's disease, tests of memory, attention, language, visuospatial, and constructional abilities were administered, and the level of acetyl levocarnitine was measured in the cerebrospinal fluid. Patients were then randomly assigned to receive acetyl levocarnitine hydrochloride (2.5 g/d for 3 months followed by 3 g/d for 3 months) or placebo. After 6 months, the acetyl levocarnitine group demonstrated significantly less deterioration in timed cancellation tasks and Digit Span (forward) and a trend toward less deterioration in a timed verbal fluency task. No differences were found in any other neuropsychological test results. A subgroup with the lowest baseline scores, receiving acetyl levocarnitine, had significantly less deterioration on the verbal memory test and a significant increase in cerebrospinal fluid acetyl levocarnitine levels compared with those receiving placebo. These results suggest that acetyl levocarnitine may retard the deterioration in some cognitive areas in patients with Alzheimer's disease and stress the need for a larger study of this drug. PMID- 1444881 TI - Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer's disease. Pathophysiologic implications. AB - Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD. PMID- 1444882 TI - Agraphia in dementia of the Alzheimer type. AB - This study describes graphic errors made in writing a simple sentence in 368 healthy older adults and individuals in different stages of dementia of the Alzheimer type. Errors of agraphia were present in both healthy and demented people and, in general, increased with the severity of dementia. The errors of agraphia were not correlated with measures of aphasia or psychometric measures of language and motor performance. Writing skill may represent procedural memory, and agraphia errors indicate alterations in long-term memory in dementia of the Alzheimer type. PMID- 1444883 TI - Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease. AB - OBJECTIVE: To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. DESIGN: Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months. SETTING: Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. SUBJECTS: Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. INTERVENTIONS: None. OUTCOME MEASURES: Onset of chorea and imaging results. RESULTS: The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. CONCLUSIONS: The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism. PMID- 1444884 TI - Neurologic and neuropsychological manifestations of human immunodeficiency virus infection in intravenous drug users without acquired immunodeficiency syndrome. Relationship to head injury. AB - We examined 99 human immunodeficiency virus (HIV)-negative and 122 HIV-positive intravenous drug users (IVDUs) without acquired immunodeficiency syndrome (AIDS) to determine whether HIV-positive IVDUs had more neurologic and neuropsychological impairment than their HIV-negative counterparts. Controlling for age, education, drug use, history of head injury, and interactions between head injury and HIV status and drug use, HIV-positive subjects had more extrapyramidal signs and frontal release signs. These findings persisted when asymptomatic HIV-positive subjects without systemic signs of infection and HIV negative subjects were compared. Neurologic findings were more severe in those with more systemic illness. Among those reporting a history of head injury with loss of consciousness, neuropsychological performance was significantly worse in the HIV-positive subjects, and this increased with severity of illness. This was not true in the group without head injury, suggesting an interaction between history of head injury and the seropositive state. No relationship was noted between head injury and either drug use or HIV state. Therefore, subtle neurologic and neuropsychological abnormalities may precede clinical evidence of AIDS in IVDUs and may be more evident in those with head injury. PMID- 1444885 TI - Alcohol exacerbates behavioral and neurochemical effects of rat spinal cord trauma. AB - Acute alcohol intoxication may exacerbate the consequences of central nervous system trauma, although the mechanism is uncertain. Effects of acute ethanol administration on behavioral and neurochemical changes were examined in rats after traumatic spinal cord injury. Survival rates were reduced and posttraumatic neurologic function worsened in ethanol-treated as compared with saline-treated controls. Ethanol-treated rats had significantly lower tissue levels of excitatory amino acids and higher levels of free fatty acids, thromboxane, and lactic acid than did controls. Tissue magnesium concentration was significantly reduced by trauma and recovered more slowly in ethanol-treated rats. Enhanced phospholipid hydrolysis with free fatty acid and thromboxane accumulation, increased release of excitatory amino acids, and decreased tissue magnesium levels may each serve to worsen secondary tissue damage and diminish neurologic recovery after spinal cord injury associated with acute alcohol intoxication. PMID- 1444886 TI - Distinct syndromes of hemineglect. AB - Hemineglect was assessed in 34 patients with right-hemisphere stroke using a letter-cancellation task and a line bisection task. No significant correlation (r = .39) was found between scores on the two tests. Ten patients who showed neglect on the cancellation task but performed normally on line bisection had frontal or deep lesions. Eleven patients with posterior lesions deviated rightward on line bisection; several of these had minimal or no cancellation deficit. A nonmotor task involving judgment of a bisected line was also performed abnormally by six patients with line bisection shift, suggesting that such shift does not result from a motor response asymmetry. We propose that separable components of the neglect syndrome may be associated with damage to discrete areas of the nondominant hemisphere. PMID- 1444887 TI - Flexor plantar responses in children with upper motor neuron lesions. AB - The usual plantar response in upper motor neuron lesions is extensor. As flexor responses were seen in a number of children with these lesions, a formal study was undertaken to assess the plantar reflex in affected children. Fifty-seven children with spastic cerebral palsy were examined. Ten had hemiplegias, so a total of 104 limbs were tested. Eighty-four (80.8%) of these had flexor and 12 (11%) had extensor responses. Half (3.9%) of the remaining eight responses were mute and half were variable. While exceptions to the extensor rule are known, this marked predominance of flexor responses is unusual. This may be the result of damage inflicted on the immature nervous system before full connections and myelination have been completed. Further studies, involving children who have sustained brain damage at different ages, will be needed to elucidate the various mechanisms involved. PMID- 1444888 TI - Acute intracranial lesions and respiratory sinus arrhythmia. AB - We studied the effects of acute intracranial lesions on the respiratory sinus arrhythmia (RSA) with the use of computerized measurements of the ratio of expiratory to inspiratory R-R intervals. The RSA was reduced below the 95th percentile for age in 20 of 27 patients, an average of 2 days after an acute event. Only four patients, without neurological deficits, had a normal RSA. Two patients, with signs of secondary brain-stem compression from a mass, had an increased RSA, without the bradycardia that is usually associated with Cushing's response. Twenty-three patients had their respiratory rate controlled by positive pressure ventilation during testing, and our preliminary findings suggested that this was not responsible for reducing the RSA. Acute intracranial lesions caused a diminished RSA, perhaps by reducing supratentorial influences on vagal cardioinhibitory activity. In contrast, once signs of secondary brain-stem compression occur, the RSA is greatly increased while the heart rate remains unchanged, offering a possible method of noninvasive monitoring for this complication. PMID- 1444890 TI - Perception of forces exerted by jaw and thumb. AB - By comparing the results of force matching between the jaw and the thumbs, whether subjects have any knowledge about the magnitude of exerted forces irrespective of the motor system was studied. Subjects were asked to match isometric forces of their own choice exerted by flexion of one of the thumbs with the jaw, and the other way around. The results were compared with control experiments in which subjects matched forces exerted by flexion of one of the thumbs with the other thumb and vice versa. None of the subjects was able to match correctly in all experimental conditions. All subjects displayed inconsistent matching behaviour, showing a mixture of correct matching and mismatching. This holds both for absolute matches (in N), and for matches relative to the maximal forces. The results show that knowledge about the magnitude of exerted forces is different for the jaw and the thumbs. Sensations about isometric forces exerted by the jaw or the thumbs are different within each subject and from subject to subject. PMID- 1444889 TI - Maintenance of amelogenin gene expression by transformed epithelial cells of mouse enamel organ. AB - Electroporation was used to introduce foreign genes into cells derived from the mouse enamel organ epithelia (EOE). Optimal conditions for this electroporation were established. The introduction of a plasmid construct bearing the coding region for the large T-antigen from polyoma virus into EOE cells permitted the establishment of a derivative cell line that has the following characteristics: (1) the cells could be passaged many times; (2) they expressed a keratin containing cytoskeleton; and (3) approx. 60% of the cells expressed amelogenin, a tissue-specific gene product unique to ameloblasts. Potential uses for such a cell line include analysis of: (1) the upstream regulatory regions required for temporally and spatially restricted expression of amelogenin; (2) the post translational modification of amelogenin in synchronized cells and (3) the organization and biomineralization of enamel extracellular matrix in monolayer culture. PMID- 1444891 TI - Effects of epidermal growth factor and transforming growth factor-beta on insulin induced differentiation in rat dental pulp cells. AB - An established pulp cell line (RPC-C2A) was used to study the regulatory effect of insulin on dentinogenesis. Insulin increased alkaline phosphatase activity and the incorporation of [2,3-3H]-proline into collagenase-digestible protein, whereas [3H]-thymidine incorporation by the cells was inhibited by insulin. The enhancing effect of insulin on alkaline phosphatase activity was inhibited by epidermal growth factor (EGF) or transforming growth factor-beta (TGF-beta). The stimulatory effect of insulin on collagen synthesis was also inhibited when insulin was combined with EGF, but was accelerated by the addition of TGF-beta. Inhibitory effects of insulin on the [3H]-thymidine incorporation were potentiated by EGF, though EGF alone strongly increased the effect; whereas the addition of TGF-beta had no significant effect on the insulin action. These findings suggest that insulin may be concerned with the differentiation of pulp cells in dentinogenesis and that EGF or TGF-beta regulate the insulin effects. PMID- 1444892 TI - Comparison of the effects of galactose and glucose on the pH responses of human dental plaque, salivary sediment and pure cultures of oral bacteria. AB - Comparisons made in dental plaque in vivo demonstrated that galactose produces a significantly smaller decrease in pH than does glucose. In vitro studies with plaque, salivary sediment and pure cultures of oral bacteria done in the absence of intraoral factors such as flowing saliva confirmed this lesser acidogenicity of galactose. Pure culture showed that most of the bacteria tested produce a moderate to large decrease with glucose but only a few do so with galactose; most produced a moderate to little or no pH response with this sugar. This suggested that the smaller decreases in pH seen in plaque in vivo with galactose were largely due to bacterial differences, basically that resident micro-organisms individually have less galactolytic than glucolytic capability. Variance in capability was attributed to differences in membrane transport processes and metabolic pathways normally available to bacteria for galactose and glucose catabolism. In the in vitro experiments, because plaque and sediment can produce base as readily as they can produce acid, the nitrogenous substrates identified earlier as major stimulants of base formation, urea and arginine, were concurrently examined for their attenuating effects on the galactose and glucose pH responses. These showed, consistent with its lesser acidogenicity, that galactose could be countered more readily in its ability to reduce the pH by either of these two base-forming substrates than could glucose. The effects were different with urea and with arginine, urea attenuation occurred sooner and arginine attenuation later in both plaque and sediment. The corresponding acid base pH profiles for pure cultures were different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1444893 TI - Isolation of granule proteins from cells of the dental follicle and stellate reticulum of rat mandibular molars. AB - The presence of a dental follicle is required for eruption of teeth of limited eruption but it is uncertain if any molecules indigenous to the follicle regulate this eruption. However, electron-dense granules of unknown composition and function are present in the fibroblasts of the dental follicle of rat molars, as well as the adjacent stellate reticulum, before and during tooth eruption. Here the granules have been isolated; two proteins, of 167 and 200 kDa, have been determined by biochemical and immunological methods to be major components of the granules. PMID- 1444894 TI - Granule proteins of the dental follicle and stellate reticulum inhibit tooth eruption and eyelid opening in postnatal rats. AB - Electron-dense granules within cells of the dental follicle and stellate reticulum of rat mandibular molars can be isolated; their major components are 167 and 200 kDa proteins. Injecting these granule proteins into postnatal rats results in a delay of incisor eruption and eyelid separation. These inhibitory effects were most pronounced with the 167 kDa protein (a delay of 3 days in incisor eruption and of 2 days in eyelid opening) and were opposite to the stimulatory effects of epidermal growth factor. Thus, these granules may play an inhibitory part in tooth eruption. PMID- 1444895 TI - Task-related behavior of motor units in different regions of the human masseter muscle. AB - Muscle activity patterns appear to vary regionally in the human masseter. However, studies of motor-unit (MU) behaviour in the masseter have been hampered by the absence of a reliable technique for locating needle-electrode recording sites. Here, voluntary MU behaviour patterns were examined in verified regions of the muscle. Activity was recorded from 50 stereotactically mapped masseter MUs. Initially, the task specificity of each MU was determined. Then for each task, the lowest sustainable firing frequency (LSFF) was reached by slow increases and decreases in voluntary firing rate, followed by sustained firing at the lowest possible rate. Pulse-discrimination and digital sampling of consecutive interspike intervals were used to measure the LSFF for each task to which the MU contributed. All MUs fired continuously during the performance of 2-6 separate tooth-contact and postural tasks. There were significant differences between LSFFs for the tasks performed by 47 units. Masseter MU task profiles appear to vary regionally, and are dependent on jaw position, the bite point along the tooth row, and the direction of effort. Descending neural drive to masseter MUs thus seems to be highly task dependent, even when the unit firing rate is controlled voluntarily at its LSFF. PMID- 1444896 TI - Masticatory muscle fatigue: endurance times and spectral changes in the electromyogram during the production of sustained bite forces. AB - The purpose of this experiment was to determine if the characteristics of fatigue observed in the limb muscle system are also evident in the muscles of mastication, specifically, the masseter and temporalis. Surface electrodes were placed bilaterally over the masseter and temporalis muscles of 10 adults. Each subject was instructed to maintain maximal and six levels of submaximal incisal bite forces for as long as possible. The power density spectrum of the electromyographic signals for each muscle was calculated at the onset and failure of the task. The decrease in endurance time with an increase in bite force followed a pattern similar to that in limb muscles, and each muscle was characterized by a consistent reduction in the mean power frequency of the power density spectrum and a variable change in r.m.s. power. The variability of changes in r.m.s. power (which is inconsistent with changes found in the limb muscles) was explained in terms of either changes in motor-unit firing rate or the muscle's relative contribution to the generation of bite force. The analyses also demonstrated a curvilinear relationship between bite force and r.m.s. power, but no relationship between bite force and the mean power frequency of the power density spectrum. PMID- 1444897 TI - Contamination of human gingival crevicular fluid by plaque and saliva. AB - Dental plaque and saliva are both possible contaminants of gingival crevicular fluid (GCF). Plaque samples from 12 sites in four subjects who had allowed plaque to accumulate for 24-48 h were quantified using the Plaque Index and then transferred to filter paper strips for fluid volume determination using the Periotron 6000. The mean volume of fluid for plaque scores of 0 was 0.02 (+/- 0.01) microliter, whereas for plaque scores of 3 the mean volume was 0.15 (+/- 0.07) microliters. In a clinical study, GCF samples, from 19/184 subjects (10.4%) were assessed as contaminated or suspected to be contaminated with saliva, but only 28/1740 strips (1.6%) were placed in these categories of contamination. An assay to confirm salivary contamination was established, using an immunochemical, double-antibody method with sheep anti-human salivary alpha-amylase followed by peroxidase-conjugated rabbit anti-sheep immunoglobulin. The detection threshold of the assay was 7.5 ng of alpha-amylase, which represents approx. 15-25 nl of saliva. The assay was evaluated on 90 GCF samples categorized as 'known' (n = 16), 'suspected' (n = 16), or 'not' contaminated (n = 58) with saliva; 81.25, 50 61.5 and 5.2-8.6%, respectively, were positive for salivary alpha-amylase. In some GCF samples salivary contamination was in excess of 50%. It was concluded that GCF samples seen to be contaminated with saliva should be discarded, whereas samples considered free from contamination may be used with confidence. Samples suspected of contamination may require an alpha-amylase assay before further analysis. PMID- 1444898 TI - Relationship between size of distal accessory tubercles and hypocones in permanent maxillary molar crowns of southern Africans. AB - The relationships between total occlusal crown area and the basal cusp areas of the accessory distal tubercle (C5) and the hypocone were analysed in molars of complete upper tooth rows of a southern African sample. While non-parametric tests between hypocone and C5 sizes did not yield statistically significant results, analyses of metrical data revealed a trend towards compensatory interaction between both cusps. Contrary to previous reports the size of C5 was found to be independent of total crown area. As enamel is thickest on cusp tips there may be a functional reason for the frequency of occurrence of the distal accessory tubercle. The pattern of distribution of the hypocone and C5 within a tooth row may be related to the occlusal wear pattern in Homo, which exhibits a marked lingual slope of wear in anterior molars and a horizontal or even buccal slope in posterior teeth. PMID- 1444899 TI - The effects of magnesium and fluoride on the hydrolysis of octacalcium phosphate. AB - The adsorption of Mg ions on octacalcium phosphate (OCP) and its effect on OCP hydrolysis, with and without F, were studied. The Mg adsorption isotherm was fitted by the Langmuir model with an affinity constant of 0.74 ml/mumol and maximum number of sites, 31.19 mumol/g. The hydrolysis rates were measured in a pH stat by titration of base and were strongly temperature dependent. The products were examined by X-ray diffraction and chemical analysis. OCP hydrolysis takes place in two stages: the fast initial process, which is attributed to the surface topotactical conversion, followed by the main, slower process, which involves the nucleation and crystal growth. Mg ions, as 1 mmol/l MgCl2, prevented the initial surface reaction and decreased the nucleation rate dramatically and the growth rate slightly; F increased the rates of surface reaction and both the nucleation and crystal growth processes. The Ca/P ratio (1.53) and the line broadening in the X-ray diffraction patterns of the apatitic products were not significantly affected by the F. Mg also did not affect the Ca/P ratio and the line broadening at (002) diffraction, but decreased the line broadening at (310) diffraction. PMID- 1444900 TI - Enhancement by cyclosporin A of metastasis from hamster cheek pouch carcinoma. AB - Daily intravenous administration of 50 mg/kg cyclosporin A (CsA), after excision of cheek pouch tumors induced with 9,10-dimethyl-1,2-benzanthracene (DMBA), enhanced the incidence of cervical lymph node metastasis to 93%, a significant increase over the rates observed for animals receiving a dosage of 25 mg/kg (43%), and for control animals receiving no CsA (40%). No significant effect was evident on the growth rates of the metastasized tumour cells in the lymph node. PMID- 1444901 TI - Zinc and macular degeneration. PMID- 1444902 TI - The Collaborative Corneal Transplantation Studies. PMID- 1444904 TI - Radial keratotomy and corneal scarring. PMID- 1444903 TI - Corneal endothelial toxicity of DexSol corneal storage medium supplemented with povidone-iodine. PMID- 1444905 TI - Sterile stromal melt of epikeratoplasty lenticule. PMID- 1444906 TI - Polymegethism of the corneal endothelium in an eye with long-standing ptosis. PMID- 1444907 TI - Conjunctival photocoagulation in Sturge-Weber syndrome. PMID- 1444908 TI - Physicians refer 9% of patients. PMID- 1444909 TI - Screening preschool children to detect visual and ocular disorders. PMID- 1444910 TI - The increased risk of ulcerative keratitis among disposable soft contact lens users. AB - Previous controlled studies on contact lens-associated ulcerative keratitis were performed before the widespread use of disposable contact lenses. Therefore, a controlled study was undertaken to determine the relative risk of ulcerative keratitis among users of disposable soft contact lenses compared with the risk among users of other lens types. Forty-six consecutive cases of contact lens associated ulcerative keratitis were identified between January 1990 and June 1992 at a corneal specialty practice in western Michigan. Five controls, matched to each case patient according to the dispensing data and prescribing practitioner, were obtained for 42 cases (91%). Users of daily-wear rigid gas permeable lenses had the lowest risk of developing ulcerative keratitis. Relative to users of daily-wear soft contact lenses, users of extended-wear soft contact lens had an age-adjusted and sex-adjusted relative risk of 1.87 (95% confidence interval, 0.61 to 5.71). Disposable soft contact lens users had the highest risk of developing ulcerative keratitis, with an adjusted relative risk of 14.16 (95% confidence interval, 5.47 to 37.63) compared with daily-wear soft contact lens users and 7.66 (95% confidence interval, 2.27 to 25.83) compared with conventional extended-wear soft contact lens users. PMID- 1444911 TI - Risks of keratitis and patterns of use with disposable contact lenses. AB - Disposable soft contact lenses have been marketed as a safer alternative to conventional soft lenses. We undertook a case-control study of patients attending the casualty unit of an eye hospital to quantify the relative risk of keratitis in disposable lens wear and to establish associated patterns of use. All eligible contact lens users were identified and asked to complete a questionnaire (n=242). Keratitis, microbial or sterile, was the most common complication in disposable lens users, occurring in 16 of 41 subjects. The relative risks for all lens types were estimated by comparison with rigid lenses (the referent). Both extended- and daily-wear disposable lenses were associated with higher risks of keratitis than other lens types including conventional extended-wear lenses. Poor hygiene, disinfectant system failure, and lens type may all account for these statistically significant trends. PMID- 1444912 TI - Electro-oculography in autosomal dominant vitreoretinochoroidopathy. AB - Thirteen members of a family presumed to be harboring the gene for autosomal dominant vitreoretinochoroidopathy were examined. In four affected members, electro-oculography demonstrated marked reduction of the Arden ratio (range, 1.1 to 1.5; normal, > or = 1.8), despite electroretinographic evidence of mildly affected rod function and normal cone function. These findings suggested that a diffuse disturbance of the photoreceptor-pigment epithelium complex may have been present prior to wide-spread loss of photoreceptor function in the affected members of this family. As in previously described families, the pattern of inheritance appeared consistent with autosomal dominance. PMID- 1444913 TI - Foveal cone electroretinograms in patients with central visual loss of unexplained etiology. AB - Foveal cone electroretinograms (ERGs) were recorded in five patients (aged 24 to 66 years) referred because of central visual loss of unexplained etiology. These patients had no family history of visual loss and no diagnostic fundus abnormalities seen on ophthalmoscopy or fluorescein angiography. Foveal cone ERGs were elicited with a 4 degrees white stimulus flickering at 42 Hz centered within a steady 10 degrees white surround presented through the dilated pupil to the fovea by a hand-held, dual-beam stimulator-ophthalmoscope. All five patients showed reduced foveal cone ERG amplitudes. Their abnormal responses were similar to those previously reported in cases of clinically apparent macular degeneration and contrasted with previously reported normal responses in patients with optic atrophy or strabismic amblyopia. The progressive loss of central vision as determined by history and these subnormal foveal cone ERG amplitudes suggest that these patients have a form of macular degeneration. PMID- 1444914 TI - Standardized full-field electroretinography. Normal values and their variation with age. AB - Full-field electroretinograms were obtained in 269 normal subjects with the International Standardization Protocol endorsed by the International Society for Clinical Electrophysiology of Vision and the National Retinitis Pigmentosa Foundation Inc. Log rod and cone amplitudes decreased exponentially with age in adults; amplitudes declined to one half those in the young adult level (ages 15 to 24 years) by ages 69 and 70 years for rod and cone responses, respectively. B wave implicit times increased with age for all responses. Lower limits of normal peak-to-peak amplitude and upper limits of normal b-wave implicit time (P < .05) were determined for each decade from birth to age 79 years. Naka-Rushton functions relating rod peak-to-peak amplitude to retinal illuminance were determined in 50 normal subjects. A significant decline in the log maximum asymptotic amplitude with age accounted for most of the amplitude decline in the standard protocol rod response. The average value of log k, the semisaturation constant, was only 0.1 log unit higher at age 70 years than at age 20 years, consistent with previous studies showing little decrease in photopigment optical density with age. PMID- 1444915 TI - Leber's hereditary optic neuropathy. Clinical manifestations of the 3460 mutation. AB - Leber's hereditary optic neuropathy is associated with three different point mutations of mitochondrial DNA that appear to be pathogenetic for the disease. These mutations affect nucleotide positions 3460, 11,778, and 15,257. We reviewed the clinical characteristics of 12 visually symptomatic patients from nine families with the 3460 mutation and compared them with previously published characteristics of symptomatic patients with the 11,778 mutation. The patients with the 3460 mutation were similar to the patients with the 11,778 mutation in most clinical parameters. However, the patients with the 3460 mutation had a higher incidence of visual recovery (20% vs 4%, P = .001), a higher percentage of pedigrees with more than one affected family member (78% vs 43%, P = .011), and a greater frequency of tobacco and alcohol abuse. The difference in visual prognosis between these two mutations and the need for modification of possible risk factors provide added significance to genetic testing for Leber's hereditary optic neuropathy. PMID- 1444916 TI - Ocular findings associated with rhodopsin gene codon 267 and codon 190 mutations in dominant retinitis pigmentosa. AB - Two members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-thymine mutation in the second nucleotide of codon 267 in the rhodopsin gene that resulted in a proline-to-leucine change. Two members of another family with autosomal dominant retinitis pigmentosa showed a guanine-to thymine mutation in the first nucleotide of codon 190 in the rhodopsin gene that resulted in an aspartate-to-tyrosine change. Three members from a third family with autosomal dominant retinitis pigmentosa were also found to have a mutation in codon 190; however, this guanine-to-adenine mutation in the first nucleotide of codon 190 resulted in an aspartate-to-asparagine change. The relatively less severe functional retinal impairment in our patients with a transmembrane codon 267 rhodopsin gene mutation is generally comparable with that observed in a previously described codon 58 transmembrane mutation. The two families with different intradiscal codon 190 mutations showed a considerable difference in severity of their disease. PMID- 1444917 TI - Procollagen II gene mutation in Stickler syndrome. AB - Four affected members of a family with Stickler syndrome were found to have a single base-pair deletion resulting in a translational frameshift in exon 40 of the procollagen II (COL2A1) gene on chromosome 12. This mutation was not seen in any of five clinically unaffected family members or in any of 15 unrelated control patients. All affected members had distinctly abnormal vitreous syneresis and all had retinal perivascular pigmentation. Retinal detachments occurred in three of the four affected patients. Three of the four affected patients had peripheral cortical "wedge" cataracts, and the fourth had extensive nuclear sclerosis. Abnormalities of the soft palate were found in all four affected patients. All patients reported severe joint pains, and epiphyseal dysplasia was found radiographically in all patients. PMID- 1444918 TI - The absorption of mixtures of air and perfluoropropane after pars plana vitrectomy. AB - The duration of mixtures of perfluoropropane and air (0% to 20% C3F8) were analyzed in 206 eyes following pars plana vitrectomy for a variety of vitreoretinal disorders using a noninvasive model for calculating the intraocular gas bubble volume. The accuracy of the noninvasive model was tested by comparing the estimated bubble volume with the actual volume withdrawn from 12 eyes with intraocular gas bubbles undergoing a subsequent vitrectomy. The method for estimating intraocular bubble volume had a mean difference between the actual and estimated bubble volume of 0.1 +/- 0.35 mL. The half-life of air (0% C3F8) was 1.3 +/- 0.1 days; 5% C3F8, 4.2 +/- 0.1 days; 10% C3F8, 6.5 +/- 0.2 days; 15% C3F8, 8.0 +/- 0.6 days; and 20% C3F8, 12.5 +/- 1.1 days. The difference between each half-life was statistically significant (P < .01). Linear regression analysis of the half-lives of C3F8 mixtures of up to 20% C3F8 showed a linear increase in half-lives with increasing concentrations of C3F8. The duration of intraocular gas tamponade can be controlled by selecting the appropriate concentration of air and C3F8. PMID- 1444919 TI - Eyelid anatomy revisited. Dynamic high-resolution magnetic resonance images of Whitnall's ligament and upper eyelid structures with the use of a surface coil. AB - We used a new radiofrequency surface coil and complementary software in eyelid magnetic resonance imaging. This custom-designed coil allows visualization of the eyelid structures in submillimeter resolution, providing detailed delineation of such structures as the orbital septum, levator aponeurosis, Muller's muscle, and orbital septa. The effect of Whitnall's ligament on the levator aponeurosis can be observed as a "tenting" of the aponeurosis; the change in vector force is persistent in upgaze and downgaze. This technology will allow accurate dynamic studies of eyelid anatomy in patients with various anatomically based eyelid diseases, before and after surgery, making it possible to test in vivo longstanding theories of normal and pathologic eyelid physiology. PMID- 1444920 TI - Nonulcerative complications of contact lens wear. Relative risks for different lens types. AB - A case-control study was used to evaluate the relative risk (RR) of acute contact lens-related disorders. The study sample comprised new patients wearing contact lens presenting at the accident and emergency department at Moorfields Eye Hospital, London, England, in 12 months. Disorders were classified by pathogenesis. Compared with gas-permeable hard contact lenses (the referent), extended-wear soft contact lenses were related to the largest overall RR for any complication (2.7 [95% confidence limits, 1.73, 4.16]), whereas for daily wear soft contact lenses the overall RR was 1.3 (confidence limits, 1.0, 1.72). Relative risks were greatest for extended-wear soft contact lens wearers with metabolic disorders (2.1 [confidence limits, 1.28, 3.4]) and for such wearers with sterile infiltrates (2.4 [confidence limits, 1.22, 4.84]). Among those using daily wear contact lenses, RR was highest for those with toxic/hypersensitivity disorders (5.9 [95% confidence limits, 3.27, 10.49]). Severe complications involving greater morbidity occurred more frequently with extended-wear soft contact lenses. This could be reduced by selecting a more appropriate lens type to correct low refractive errors. PMID- 1444921 TI - Binocular fusion and stereopsis associated with early surgery for monocular congenital cataracts. AB - Despite improved visual acuity results in infants undergoing early surgery for monocular congenital cataracts, virtually all reports indicate a lack of binocular vision and the presence of strabismus in these patients. We report herein the presence of motor fusion and stereopsis in patients who have undergone early surgery for monocular congenital cataracts. Of 13 patients with congenital cataracts who were operated on by age 9 weeks, five (38%) had essentially straight eyes and evidence of motor fusion with a minimum of 1 year of follow-up. Three (60%) of five patients demonstrated sensory fusion, two with Titmus testing and one with Randot Stereo Acuity (Stereo Optical Co Inc, Chicago, Ill) of 250 seconds of arc. We conclude that binocular fusion and stereo visual acuity are obtainable in patients with monocular congenital cataracts. PMID- 1444922 TI - Optic nerve aplasia. AB - Optic nerve aplasia is a rare congenital defect invariably associated with other ocular or systemic disorders. We examined a 3-year-old girl with monocular microphthalmos who had optic nerve aplasia on histopathologic examination of the eye after enucleation. Magnetic resonance imaging verified the presence of unilateral optic nerve aplasia, and demonstrated hemichiasmal hypoplasia on the affected side and bilateral optic tracts. The visually evoked cortical response revealed increased signals over the occipital cortex ipsilateral to the aplastic nerve, suggesting misdirection of axons from the temporal retina of the normal eye. The visual pathway in unilateral optic nerve aplasia may assume a primitive form of neuronal organization characterized by an increase in contralateral retinogeniculostriate projection. PMID- 1444923 TI - Toxicity of intravitreous ceftazidime in primate retina. AB - Squirrel monkeys were anesthetized and given intravitreous injections of 0.1 mL of balanced salt solution containing 0 mg (two eyes), 1 mg (three eyes), 2.25 mg (three eyes), or 10 mg (three eyes) of ceftazidime, a third-generation cephalosporin that provides excellent coverage for gram-negative infections. Ophthalmoscopic examinations were performed 48 hours after the injections and results were completely normal in all eyes except for those that were injected with 10 mg of ceftazidime, all three of which showed the appearance of cystic change in the macula. The monkeys were killed and the eyes were removed and examined by light and electron microscopy. All eyes were normal by light microscopy except for those injected with 10 mg of ceftazidime, which showed disruption of photoreceptors (primarily outer segments) in the foveas with cystic changes in all three and macular holes in two of three. Electron microscopy showed mild swelling of mitochondria and perinuclear halos around photoreceptor nuclei in both control eyes and in eyes injected with 1 and 2.25 mg. An eye injected with 10 mg showed severe damage to central photoreceptor outer segments consisting of disruption of plasma membranes and accumulation of intracytoplasmic granular material. Inner segments showed mild changes and there was loss of apical microvilli of the retinal pigmented epithelium. The inner retina was normal. These data suggest that high doses of intravitreous ceftazidime show toxicity primarily to photoreceptor cells, but a dose of 2.25 mg is safe as studied in this model and can be used instead of intravitreous aminoglycosides that have a narrow therapeutic window. PMID- 1444924 TI - Histopathologic characteristics of diode laser-induced chorioretinal adhesions for experimental retinal detachment in rabbit eyes. AB - A retinal break and localized retinal detachment were induced in 10 rabbit eyes. The retinal break was treated within regions of detached retina using diode laser transscleral retinopexy (four eyes), diode laser indirect ophthalmoscopy (two eyes), or retinocryopexy (two eyes). Two eyes were left as untreated controls. The clinical and histopathologic effects were studied 1 day and 3 weeks after initial treatment. Suitable chorioretinal adhesions were induced with all treatment modalities. The extent of tissue effects was greater in cryopexy and smaller in laser treatment. The histopathologic characteristics of the lesions induced by diode laser indirect ophthalmoscopy were similar to those seen with transscleral diode treatment and were more focal than those seen with cryopexy. Transscleral and transpupillary diode laser photocoagulation were effective in inducing chorioretinal adhesions in detached retina in this experimental model in rabbits. PMID- 1444925 TI - Morphometric analysis of macular photoreceptors and ganglion cells in retinas with retinitis pigmentosa. AB - There have been a number of histopathologic studies of retinas that were taken post mortem from patients with retinitis pigmentosa (RP), but few have addressed the question of transneuronal degeneration of ganglion cells secondary to photoreceptor death. We studied sectioned maculae that were obtained from 41 patients with different genetic forms of RP: autosomal dominant (n = 11); X linked (n = 9); and simplex (n = 21). We also studied sectioned maculae that were taken from 20 age-matched normal subjects. We counted cell bodies in the photoreceptor and ganglion cell layers at 100-microns (0.35 degrees) intervals from the foveola to 1500-microns eccentricity and compared the mean cell counts among each group with RP. Each RP type had significantly fewer (P < .05) photoreceptors than those of the control group at each 100-microns interval. At eccentricities of 700 to 1500 microns, the retinas with X-linked and autosomal dominant RP had significantly fewer (P < .05) ganglion cells than those of the control group; the simplex RP mean ganglion cell counts were significantly lower (P < .05) than those of the control group, from 1000 to 1500 microns. The mean photoreceptor and ganglion cell counts had a .43 correlation (P < .001) in the zone of 700 to 1500 microns, consistent with transneuronal ganglion cell degeneration. Current experimental attempts to restore vision in diseased retinas by simulating or replacing photoreceptors are based on the premise that ganglion cells are retained after photoreceptor death. Our findings support this assumption. PMID- 1444926 TI - Subcutaneous air after closure of a tracheocutaneous fistula. PMID- 1444927 TI - Cataract extraction in eyes filled with silicone oil. AB - A surgical technique for cataract extraction in eyes filled with silicone oil was developed that has two major objectives: removal of the entire cataractous lens and complete preservation of the silicone oil volume. A regular extracapsular cataract extraction or phacoemulsification is performed, and the incision is closed with the final sutures. All steps are performed under continuous positive pressure achieved with an anterior chamber maintainer connected to a bottle of balanced saline solution. An inferior basal iridectomy is created with a vitrectomy probe, and the posterior capsule is then slowly pulled out through the limbal incision with intraocular forceps, again under positive pressure, in an eye that is actually a closed system, without any loss of silicone. This step results in transformation of the extracapsular cataract extraction condition into an intracapsular cataract extraction condition. The described technique was successfully performed in nine eyes. In the younger patients, the whole procedure was completed through two very small limbal openings. PMID- 1444928 TI - Repair of inadvertent conjunctival filtering blebs with a scleral flap. AB - We describe a new technique to correct inadvertent conjunctival filtering blebs. This method creates a partial-thickness scleral flap to seal the region of the excised fistula. Closure of this flap with sutures permanently covers the fistula and eliminates any route for recurrence of the bleb or downgrowth of epithelium. No complications have been associated with this procedure, which has been used in more than 10 cases during the last 3 years. PMID- 1444929 TI - The mouse as a model for human audition. A review of the literature. AB - The mouse has several distinct advantages as an experimental model for human audition. Mice and humans express a similar presbyacusic and ototraumatic pattern. Several genetic mouse models also exist for conditions resembling human auditory disorders, such as otosclerosis. This paper reviews the strains of inbred mice (e.g. the CBA/J) which have recently been used as models for the normal human auditory system, describing their deficiencies. It is suggested that the F1 offspring of CBA/CaJ and AU/SsJ inbred mice would have advantages over existing models. PMID- 1444930 TI - Auditory brainstem function of the F1 offspring of the cross of CBA/CaJ and AU/SsJ inbred mice. AB - Inbred strains of laboratory mice have several distinct advantages as models for examining conditions that influence the human auditory system, but the CBA/J mouse which has most often been used as a normal model has recently been found to have several disadvantages. This paper is the first report of the auditory brainstem responses (ABRs) of the F1 offspring of CBA/CaJ and AU/SsJ parents. At midlife, high-frequency ABR thresholds are lower in the F1 than in either parental genotype. Tuning curves obtained by forward masking of the ABR also display heterosis, i.e. they are narrower in the F1 than in either parental strain. PMID- 1444931 TI - Influence of masker bandwidth on binaural masking level differences. AB - Masking level differences (MLDs) were investigated using masking noise with 160 Hz (amplitude-modulated noise) and 600 Hz (filtered-random noise) bandwidth. One hundred normally hearing subjects received the MLD test under both types of noise. Significant differences between noise types were observed in both N0S pi and N pi S0 conditions; MLDs were larger in amplitude-modulated noise. Consideration of these differences would indicate that older MLD norms based solely on filtered-random noise are invalid for amplitude-modulated noise especially where bandwidth differences in the noise exist. Were the norms for 600 Hz-wide filtered-random noise to be applied to results of MLD testing performed using 160-Hz-wide amplitude-modulated noise, patients with lesions in the central auditory pathway might exhibit normal or borderline normal results. Clinical MLD norms established on one type of noise should not be used to interpret MLD results obtained using a different type of noise. PMID- 1444932 TI - Effect of hearing aids on speech perception in noisy situations. AB - Hearing-impaired people often complain about poor speech intelligibility when they are in noisy surroundings. Several authors have published data suggesting that hearing aids add distortion to the signal and thus make speech less intelligible. Given the tendency of people to speak louder in competing noise, it means that some patients might understand better in such circumstances without an aid than with an aid. The present study investigated the effect of modern commercial hearing aids on the ability of patients to understand speech monaurally in noisy circumstances. The results in general showed speech to be equally understandable with and without an aid if the effects of presentation level (amplification) are excluded. The results, however, varied considerably between patients. Statistical analysis showed that the variance could be explained primarily by the degree of high-frequency loss and the slope of the audiogram. Patients with steep sloping audiograms understand better and patients with a conductive hearing loss component understand less in noisy circumstances with a hearing aid. Speech intelligibility in noisy situations did not correlate at all with the hearing loss averaged over the mid-frequencies (500, 1,000 and 2,000 Hz) but it did correlate with the high-frequency hearing loss (2,000 and 4,000 Hz) and the slope of the audiogram, indicating the importance of high frequency emphasis in hearing aids. PMID- 1444933 TI - Cooperation of hearing-impaired elderly subjects for participation in a hearing screening program. AB - Presbyacusis, the auditory disorder which accompanies the aging process, is well known. However, the practical assistance available to alleviate the breakdown in the communication ability of the older person is unsatisfactory, and provision for public awareness of a rehabilitation strategy has not yet been established in many countries. Four hundred and ninety-eight elderly subjects, aged 65-94 years, were hearing tested in different setups, a geriatric nursing home and in the community. It was found that the need for rehabilitation was high and the willingness to participate in a hearing screening program was low even though the rehabilitation treatment was provided without charge. PMID- 1444934 TI - Natural vowel perception by patients with the ineraid cochlear implant. AB - Vowel recognition was tested in 10 patients using the Ineraid cochlear implant. The vowels were produced by a male speaker in the context 'heed, hid, head, had, hawed, hood, who'd, hud' and 'heard'. Performance varied from 34 to 93% correct. A descriptive feature system for the vowels was determined from an acoustic analysis. An information transfer analysis of these features suggested that information about the first formant frequency, vowel duration and fundamental frequency was transmitted. Information about the second and third formant frequency was transmitted less well. A sequential information transmission analysis suggested that the features of the first formant and duration accounted for nearly 80% of the information transmitted. The fundamental frequency and second formant frequency information accounted for an additional 8%. Information provided by the third formant frequency was largely redundant. PMID- 1444935 TI - Medical record content: recurring area of concern in hospital analysis. AB - This article reports on an analysis of 109 hospitals that received recommendations for improvement within their Medical Record Service when surveyed by the Australian Council on Health Care Standards (ACHS) in 1990. Seventy-five per cent of Medical Record Service recommendations made at an earlier survey had been fully implemented and 17% partially implemented by hospitals at the time of their next survey in 1990. The major area receiving recommendations for improvement was medical record content. Other areas of concern were quality assurance, organization and administration, and space for research and work within the service. Certain aspects of medical record content also appeared to be resistant to change from one survey to the next. PMID- 1444936 TI - Trends and projections for day only admissions in NSW acute hospitals. AB - The rapid increase in the number of day only admissions during the last decade has led to an increased awareness of this type of hospital admission. Health planners are now interested in which procedures are causing the increase in the day only activity and how best to accommodate it in the future. To address these issues, routinely collected hospital data were used to analyse trends in day only admissions and to extrapolate future demand via regression models. The results suggest that day only admissions will constitute 45% of all admissions to NSW acute hospitals by the year 2001. Detailed review of patient caseloads suggest that 13.5% of all patients will be potentially treatable through day surgery units, as opposed to general wards, by 2001. Assuming 80% of these potential patients actually do get treated in day surgery units, then the workload generated could be accommodated within 30 day surgery facilities. PMID- 1444937 TI - Medical audit of hysterectomy in the Hunter Area of New South Wales. AB - A computer search in the New South Wales (NSW) Department of Health statistical data base was made to obtain the medical record numbers of patients who had had hysterectomies in the public or private hospitals of the Hunter Area of the State during the years 1987-89. The medical records of patients so identified were then extracted and reviewed by a medical team. The age at and the principal indication for hysterectomy were noted in each case and these data were then compared with those for the rest of NSW. The hysterectomy rate in the Hunter Area was 66.5 per 10,000 women aged 15 years or more, compared with a rate of 33.8 per 10,000 in the rest of NSW. When the 9.04% of hysterectomies performed on patients whose domicile was outside the Hunter Area were excluded, the corrected hysterectomy rate for the area was 57.46 per 10,000 women. The commonest indications for hysterectomy were menorrhagia (25.4%) and fibroids (15.32%). The limitations of this kind of retrospective study are discussed and suggestions are made for an improved methodology to be used in a future study. PMID- 1444938 TI - Introducing a quality of service programme to hospital orderly staff. AB - Recent reshaping of health provision throughout New Zealand has brought many changes to virtually every area of the service. In some instances this has required a totally fresh approach with a different way of thinking. In others, it has meant the adaptation and remodelling of existing structures and approaches. This paper gives a brief overview of the West Auckland Health District Quality of Service Programme and, in particular, its introduction to the orderly service at Waitakere Hospital. PMID- 1444939 TI - Windows of opportunities available in tight economic times. AB - The Royal Victorian Eye and Ear Hospital has developed a culture around the Accreditation process and quality assurance. All staff members are regularly challenged to ask themselves the question, 'What are we doing now that we could do better?' During the financial year 1990-91, over 350 quality assurance programmes were undertaken addressing more than 150 individual issues. Many aspects of a clinical nature were addressed and these will be dealt with briefly. The main focus of this paper is to indicate the windows of opportunity available to hospitals in tight economic times. Programmes were undertaken in every department throughout the hospital and, in the financial year under review, savings of $351,589 were not only identified but accomplished. These savings are ongoing during the next 5 years and will amount to approximately $1.75 million. The Auxiliaries of The Royal Victorian Eye and Ear Hospital have assisted the hospital and over the last 10 years have raised $2.5 million without any direct public appeals. PMID- 1444940 TI - Use of the Injury Severity Score to monitor diagnostic accuracy in the early assessment of road trauma. AB - A retrospective review of 279 hospital admissions at two Melbourne hospitals was conducted to develop a method for identifying diagnostic error using the Injury Severity Score (ISS) as a model for clinical audit. Two scores were calculated for each patient, the first according to injuries diagnosed on initial assessment in the Emergency Department and the second according to final, confirmed diagnoses upon discharge from hospital. Diagnostic errors were identified as discrepancies between the initial and final scores. ISS discrepancies were found in 48 cases (17.2%). Some were clinically significant errors of diagnosis while others reflected inaccurate injury description or record keeping. Abdominal injuries were the most frequently missed, followed in decreasing order by spinal, thoracic, extremities (limbs), head/face and external injuries (skin and subcutaneous tissues). The frequency and pattern of injury misdiagnosis concurs with the findings of other studies. The diagnostic error rate was found to increase with injury severity and with the number of anatomic body regions involved. The authors suggest that comparing initial and final ISS provides a convenient mechanism for the audit of early diagnosis in trauma cases. PMID- 1444941 TI - The tunnel restoration--nine years of clinical experience using capsulated glass ionomer cements. Case report. AB - The clinical potential of the tunnel restoration is restrained by perceived difficulties of access to proximal caries and lack of long-term clinical data. This paper describes a technique that affords proximal access similar to that of a standard Class II cavity preparation and provides an evaluation of a technique, using capsulated glass ionomer cements. It is supported by more than nine years of clinical experience that confirms the viability of this procedure as an alternative to conventional Class II cavity restorations for initial proximal lesions. PMID- 1444942 TI - Excessive bleeding following minor trauma. Case report. PMID- 1444943 TI - Microsurgical repair of nerves injured during third molar surgery. AB - The inferior dental and lingual nerves are in close proximity to the mandibular third molar. In approximately 5 per cent of cases of the surgical removal of this tooth one or other of these nerves may be injured. In most cases the injury is reversible but in 1 per cent a distressing dysaesthesia may occur. The diagnosis of the sensory deficit is made by repeated sensory testing. If there is no improvement by six to nine months then complete spontaneous recovery will not occur. These irreversible nerve injuries can be successfully treated microsurgically. PMID- 1444944 TI - Facial palsy in the dental surgery. Case report and review. AB - Facial palsy is a relatively uncommon condition with a variety of causes including dental intervention. A brief history of two cases of facial palsy with dental implications is presented. The aetiology of facial palsy is reviewed and the management of such cases is discussed. The option of immediate treatment of Bell's palsy with prednisone is stressed. PMID- 1444945 TI - A clinical evaluation of three topical anaesthetic agents. AB - This study compared the efficacy of EMLA 5% Cream, Xylocaine 5% (lignocaine 5 per cent) and NUM (benzocaine 15 per cent, amethocaine 1.7 per cent) to a placebo in reducing the pain experience during needle insertion. In a random, double blind study three groups of twenty volunteers each had a paired topical anaesthetic/placebo placed bilaterally in the buccal sulcus of the upper premolar regions for two minutes, followed by the insertion of a standard 27 gauge needle to a depth of 5 mm. Pain experience was measured with visual analogue scales. Results showed that all three agents significantly reduced pain when compared with the placebo--EMLA (p less than 0.002); Xylocaine (p less than 0.05); NUM (p less than 0.005). PMID- 1444946 TI - Some parameters for testing deformation of elastomeric impression materials. AB - Because of conflicting published data, the temperature rise in four elastomeric materials was measured with a thermistor during setting in the oral cavity and in metal and plastic moulds of varying shapes and volumes for 'elastic set' specimens. The clinical temperature rise was 2-3 degrees C higher in the molar region than anteriorly, except for the polysiloxane. The temperature range attained in the set materials varied from 29 degrees C to nearly 35 degrees C for clinical and in vitro specimens. The average time taken by a group of operators to remove this type of impression from the mouth was five seconds. In a custom tray with light and heavy viscosity materials, the syringe material layer was only 0-0.15 mm thick and, essentially, the heavy viscosity material provided the elastic components for the impression. PMID- 1444947 TI - The effect of interface adhesion, water immersion and anatomical notches on the mechanical properties of denture base resins reinforced with continuous high performance polyethylene fibres. AB - Previous work has presented a study of the mechanical properties of denture base resins reinforced with a new type of high performance fibre. It is now shown that the substantial improvements demonstrated in those composites remain largely unaffected by a watery environment, anatomical notches, moulding pressure and other factors of denture construction. The understanding of the reinforced resins is here complemented with a detailed study of the interface strength, taking into account the various couplings occurring within the system. PMID- 1444948 TI - Choice of toothbrush: a survey of dentists' personal preferences and recommendations for patients. AB - Data on dentists' choice of toothbrush brand/type for personal use and their recommendations for patients were obtained by means of a questionnaire. Seventy nine per cent of dentists surveyed received free samples, with Oral-B comprising 33 per cent of all such samples, followed by Colgate (16 per cent) and Tek (13 per cent). Fifty-three per cent of dentists surveyed indicated they used all free samples received. Sixty-two per cent of dentists do not consider that different brushes differ significantly in their plaque-removing ability. Therefore, while an effective toothbrushing technique is important, selection of the 'correct toothbrush' from the wide range available may not be critical. The results of the present investigation provide information that is relevant to dental health education and can be applied at the chairside as well as at the broader community level. PMID- 1444949 TI - Survey of continuing dental education attendance in Western Australia. AB - A survey of attendance at continuing dental education courses convened by the University Postgraduate Dental Education Committee, University of Western Australia, and the Australian Dental Association. Western Australian Branch was collated for one calendar year. Attendances were compared relating to the number of dentists registered in the State, ADA membership, metropolitan versus rural dentists and the number of courses attended. The mandatory and voluntary options for continuing dental education are discussed in the light of the survey findings. PMID- 1444950 TI - Clinical note no. 11. Mechanical properties in bending of shape-memory wires. PMID- 1444951 TI - Effectiveness and efficiency. PMID- 1444952 TI - 'Hot pulp' syndrome. PMID- 1444953 TI - Finishing techniques for amalgam restorations: clinical assessment at three years. AB - Use of the optimum finishing technique for an amalgam restoration may enhance the marginal integrity of the restoration and discourage its unnecessary early replacement. Two hundred and twenty-eight high copper amalgam restorations in 56 patients were evaluated, using clinical assessment criteria, up to three years after placement. Each patient had received at least one carved-only amalgam, at least one immediately finished restoration, and at least one amalgam that was polished at a subsequent appointment. Regardless of the finishing technique, the restorations exhibited similar marginal integrity up to three years after placement. Polished restorations were found to have substantially superior surface texture and less likelihood of surface discoloration. No evidence was found to support the use of immediate finishing techniques. The clinical significance of these findings, with respect to the need to polish amalgam restorations, is discussed. PMID- 1444954 TI - Complications associated with maxillary nerve block anaesthesia via the greater palatine canal. AB - This paper documents the type, frequency and duration of complications associated with regional anaesthesia of the maxillary nerve via the greater palatine canal in a series of 101 patients treated in the Oral Surgery Department, United Dental Hospital of Sydney. PMID- 1444955 TI - Comparative elasticity tests for elastomeric (non putty) impression materials. AB - This study was conducted to evaluate the methods used for measuring the elastic recovery of various elastomeric impression materials. One brand from each chemical group was selected to allow relative ranking of the results from each deforming test mode. For compression tests, the polysulphide and silicone specimens made in metal moulds gave significantly less set than those made in acrylic moulds; this was not so for the polysiloxane and polyether specimens. For polysulphide and polyether materials, the set in compression was greater using the BSI balanced beam method than for an optical method without inertia or load effects; this was not so for silicone or polysiloxane materials. The elastic recovery of the materials did not alter significantly after ten minutes of strain release, except in tensile tests, where the elastic recovery continued to change for twenty minutes. The rank ordering of the deformation set showed a relative correlation for the compression test, a new tensile test method, and bend and torsion testing methods. Thus only one method is needed to determine set per cent. PMID- 1444956 TI - Prosthodontic procedures for implant reconstruction. 1. Diagnostic procedures. AB - The University of Sydney Dental School and more recently the Implant Centre have been treating patients with the Branemark Osseointegration Implant System since 1981. Success depends on close cooperation between surgeon and prosthodontist. This paper describes specific prosthodontic treatment planning procedures based on a general knowledge of prosthodontics, and detailed methods for determining the position, length and alignments of the implants for a specific case by the use of radiographic and surgical templates. PMID- 1444957 TI - The adverse effects of dental restorative materials--a review. AB - Several materials used in dentistry are described as biomaterials. Owing to the intimate contact of these materials with the oral tissues, they should possess a high degree of biocompatibility. However, some materials may exhibit adverse effects, causing both local and general pathological changes, even though the occurrence seems to be relatively low. It is, therefore, the dentist's responsibility to be aware of the potential adverse effects of these materials and to take precautions to protect the patient form such effects. The purpose of this article is to review the potential adverse effects of some commonly used restorative materials, mainly with regard to patients. PMID- 1444958 TI - Effect of gels containing stannous fluoride on oral bacteria--an in vitro study. AB - The purposes of this investigation were to evaluate and compare the antimicrobial effect of (1) twelve 0.4 per cent stannous fluoride (SnF2) commercial products and (2) different concentrations of SnF2 (range = 0.02 to 3.28 per cent). The antibacterial inhibitory effect of various SnF2 gels was evaluated as to their effectiveness against oral plaque bacteria including strains of S. mutans, S. sanguis, S. sobrinus, A. viscosus, A. actinomycetemcomitans, and B. intermedius. When twelve different commercial preparations of 0.4 per cent SnF2 were compared for inhibitory effect on plaque bacteria, several of the SnF2 preparations were significantly more effective in inhibiting oral bacteria (p < 0.05). With increasing concentration of SnF2, there was a comparable increase in the inhibitory effect on the oral bacteria tested (r2 ranged from 0.867 to 0.996). SnF2 at a concentration of 0.4 per cent had a similar antibacterial effect to 0.12 per cent chlorhexidine. This in vitro study demonstrated that certain SnF2 products are highly effective in inhibiting the growth of bacteria often found in plaque, and this inhibitory effect is directly related to the concentration of the SnF2. PMID- 1444959 TI - The grading of practical examinations in complete denture technology. AB - The problems associated with the grading of practical examinations are discussed and statistical analyses of two gradings are presented. Consideration is given to the difficulties of failing students who may wish to transfer to another faculty and a recommendation is made for the introduction of non-graded passes. PMID- 1444960 TI - Some social characteristics and background of first-year dental students, University of Sydney, 1976-85. AB - This paper presents some information, derived by questionnaire, on the social characteristics and background of 1148 first-year dental students at the University of Sydney for the years 1976-1985. Student entry age was 19.4 years; 27 per cent were female; 36 per cent of fathers and 24 per cent of mothers were professionals and 37 per cent of fathers and 11 per cent of mothers had attended university; parents of female students had higher educational levels than parents of male students; 55 per cent had medicine as the course of first preference. Eighty-five per cent of students entered dentistry from high school with 78 per cent from Sydney. Characteristics of students showed little change over the period 1976-1985. Some changes noted were an increase in the number of female students with fewer living in their parents' home; increase in number of students from government schools; decrease in foreign students but an increase in students (Australian citizens, or residents) born overseas, and of different ethnic backgrounds. PMID- 1444961 TI - Dental caries and periodontal disease in Fiji. AB - A national oral survey was conducted in Fiji in 1985/86. The results showed that the prevalence of caries was generally low and most commonly affected pit and fissure surfaces. Comparisons with previous surveys in 1948 and 1965 showed that the prevalence had fallen in primary teeth but remained relatively constant in permanent teeth. There were significant variations in prevalence between residential locations but not between ethnic groups. Periodontal disease was found to be a major public health problem. Except for the percentage of young children with caries-free dentitions, the current status of oral health in Fiji was generally better than that proposed in the WHO goals for the year 2000. The training of dental hygienists to help in the prevention of both dental caries and periodontal disease is discussed. PMID- 1444962 TI - Acrylic resins reinforced with highly drawn linear polyethylene woven fibres. 1. Construction of upper denture bases. AB - This paper presents a detailed description of the construction of complete acrylic upper dentures reinforced with highly drawn linear polyethylene fibres. The work forms part of a continuing project to elucidate the properties and potential of the new system. PMID- 1444963 TI - Sedation for dental procedures. PMID- 1444964 TI - Federation Dentaire Internationale policy statement on mercury and amalgam in dentistry. PMID- 1444965 TI - Name the spot. National Skin Cancer Awareness Week 23 to 29 November. PMID- 1444966 TI - Multiple sclerosis--making the diagnosis. AB - Although intensive research into all aspects of MS in the past 50 years has led to a great deal of information about pathological processes that may relate to its causation and expression, the disease is still an enigma--one of the greatest unsolved problems in medicine. Recent advances in neuroimaging and the ability to measure conduction in CNS pathways (evoked potentials) reveal subclinical effects, complementing clinical examination and frequently enabling a firm diagnosis in earlier phases of the disease than hitherto. In some situations earlier conclusive diagnosis facilitates management. But this is by no means invariably so. Clinical criteria continue to be paramount; investigative findings are supportive rather than being primarily diagnostic in their own right. Integrating this information at any one time for the maximum benefit of the patient tests knowledge and judgement. PMID- 1444967 TI - Is it Parkinson's disease? AB - The diagnosis of idiopathic Parkinson's disease is based on clinical assessment and is also a diagnosis of exclusion. A number of neurodegenerative disorders have signs in common with Parkinson's disease and are referred to as parkinsonisms. The physical findings that help to make an early diagnosis of Parkinson's disease and the atypical features that make another disease more likely are presented. PMID- 1444968 TI - Some problems in the management of the spinal cord injured patient at home. PMID- 1444969 TI - Dizziness--organic or functional? AB - The author discusses a specific case to illustrate the problem of chronic, uncompensated asymmetrical vestibular function, which can present with seemingly bizarre symptoms. Simple guidelines to distinguish between organic and functional dizziness are offered. PMID- 1444970 TI - Gait disturbances. AB - Walking is a complex motor skill and is governed by a number of interlinked pathways from the cortex above to the muscles below. The author outlines some of the important features in the history and examination of the patient with a gait disorder. PMID- 1444971 TI - Diabetes in an elderly population. A controlled study of morbidity and outcomes. AB - OBJECTIVE: To determine in an elderly diabetic population the frequency of vascular and related disorders, the mortality, and outcomes compared with a matched control group. SETTING: The Queen Elizabeth Geriatric Centre, Ballarat, Victoria. METHOD: The medical records of all diabetics admitted between 1982 and 1987 inclusive, and a control group matched for age, sex and ward of admission were studied retrospectively. The presence of associated conditions and outcome parameters were entered in to a database and analysed statistically. RESULTS: Increased prevalence in individuals with diabetes of ischaemic heart disease (2.0:1.0), cerebrovascualr accident (1.9:1.0) and hypertension (1.5:1.0). Similar death rate, cumulative bed days, discharge destination and use of discharge services. CONCLUSION: Despite the more frequent presence of clinical vascular disease, an elderly population with diabetes had the same outcomes as matched controls and did not require more bed occupancy or use of community based services. PMID- 1444972 TI - An analysis of funding for general practice research in Australia. AB - OBJECTIVE: To describe the current status of funding for general practice research in Australia. DESIGN: A descriptive survey analysing funding arrangements of research projects included in a national research database, established by the Royal Australian College of General Practitioners. SETTING AND PARTICIPANTS: Research projects involving, or directly related to, general practice that had commenced in Australia since 1 January, 1989. Responses were specifically sought from all universities, the Family Medicine Programme and the Royal Australian College of General Practitioners. MAIN OUTCOME MEASURES: Extent and source(s) of funding received or requested, or both; relationship of funding received to the following: qualification and affiliations of the principal investigator; submission of the research project towards a higher degree; subject area(s) covered by the research; study design method used; and duration of project. RESULTS: A total of 237 projects from 130 principal investigators were included in the analysis. Of these, 149 (63%) had been submitted for funding and 98 (66%) had been successful. The amount of funding ranged between $300 and $855,600. The most common source of funding was the General Practice Evaluation Programme. Research contributing towards a higher degree was associated with successfully receiving funding. Other variables, including the study design and study area, were not significantly associated with an increased success of funding. CONCLUSIONS: The total amount of funds spent on general practice research is still small, relative to the size of the workforce. However, over half of general practice research undertaken in Australia is not submitted for funding. Of the research that is submitted, the success rate of receiving funds is high. PMID- 1444973 TI - Fit-ins. Even a bad day has lessons for us. AB - It is a bad day at the office. Four patients present with intractable dilemmas: two exhibit self abusing behaviour, and the other two behave in ways that affect others. What can the GP do in these circumstances? PMID- 1444974 TI - ST elevation and review. PMID- 1444975 TI - Endotracheal and intraosseous drug administration for paediatric CPR. AB - The endotracheal and intraosseous routes are alternatives to the intravenous route of access to the circulation during emergency resuscitation. Adrenaline, lignocaine and atropine are readily absorbed from the respiratory tract via an endotracheal tube. All drugs and resuscitative fluids can be infused into the tibial bone marrow using an intraosseous needle. PMID- 1444976 TI - Clinical nutrition in primary health care. AB - Nutritional diagnosis and management are important aspects of general practice. This information, which is presented in two parts, offers the general practitioner a practical framework and an approach to nutritional advice. Part 1 outlines the clinical conditions and principles involved in nutritional diagnosis with a management approach to macrovascular disease and obesity. Part 2 covers protein malnutrition, eating disorders, osteoporosis, nutrient toxicity, cancer, inherited metabolic disorders, nutrient deficiency and diabetes mellitus. This material is based on a seminar organised by Kellogg (Australia) Pty Ltd in Melbourne in 1989 and the material is reproduced with the kind permission of Kellogg (Australia) Pty Ltd. PMID- 1444977 TI - Back posture and lifting--for older women. PMID- 1444979 TI - One and one make nothing. PMID- 1444978 TI - Variety pack. PMID- 1444980 TI - Fingertip dressing. PMID- 1444981 TI - Rural doctors. PMID- 1444982 TI - Patient education. Nipple problems while breastfeeding. PMID- 1444983 TI - Treatment of heart failure. PMID- 1444984 TI - Andrew Pattison meeting the challenge of medicine today. AB - The common thread of medical education tends to tie up the many diverse interests that constitute Andrew Pattison's working week. Although he has diversified into health education for the masses through his Doctor Toby books and his talkback radio segments, he maintains contact with his grassroots through his general practice patients. PMID- 1444985 TI - Fluids for non-dehydrated children with 'gastro'. PMID- 1444986 TI - Sexual violence. PMID- 1444987 TI - Shelf life of drugs. PMID- 1444988 TI - Spouses Support Group. PMID- 1444989 TI - Scrutinising nationalised medicine. PMID- 1444990 TI - Query on homosexual statistics. PMID- 1444991 TI - Comment on Vietnam veteran syndrome. PMID- 1444992 TI - Payments--a matter of choice. PMID- 1444993 TI - General practice--has it got a future? PMID- 1444994 TI - Common non pigmented skin cancer. AB - The scope of this article does not include many other non melanocytic skin cancers such as angiosarcoma, B cell lymphoma and atypical fibroxanthoma. These are the less common skin cancers, but no less important. If there is any doubt whether a lesion represents a skin cancer, biopsy is mandatory to establish a histopathological diagnosis so that treatment can ensue. PMID- 1444995 TI - Systemic diseases and the skin. AB - Skin lesions often give important diagnostic clues to underlying systemic disorders. A brief overview is given of the types of cutaneous presentations that may be related to an underlying organic disease. PMID- 1444996 TI - Cottonwool babies. A case history. AB - Although the adage 'common things occur commonly' is certainly true, especially in a general practice situation, there are occasions when rare or uncommon problems present themselves. In these situations the learning curve of the patient and doctor may be parallel but there is still a lot the family doctor can do to ease the suffering of the family and help in the adjustment phase. Epidermolysis bullosa can be a cruel, disfiguring and at times lethal disease, however, as Michael's case illustrates, patients deserve assessment on their own merits and with the right support and care 'cottonwool' babies can lead full and purposeful lives. PMID- 1444997 TI - Paediatric dermatology. AB - The format of this collection of skin conditions allows for only a brief discussion of the aetiology and appearance of each entity. Most of them are common skin conditions. Referring to a dermatology reference book will make this presentation more valuable. PMID- 1444998 TI - New approaches to acne. AB - In recent years, a greater understanding of the pathogenesis and improved treatment regimens have enhanced our ability to control this common and often distressing condition. The author presents a brief outline of its pathogenesis followed by a systematic approach to treatment. PMID- 1444999 TI - Psoriasis--treatment options. AB - Psoriasis can be a disfiguring and psychologically disturbing condition. Although a cure is not possible, treatment options offer relief and often remission for the patient willing to comply with them. The author looks at those options. PMID- 1445000 TI - Clinical nutrition in primary health care. Part 2: Assessment, diagnosis, presentation and management. AB - Nutritional diagnosis and management are important aspects of general practice. This information, presented in two parts, offers the general practitioner a practical framework and a approach to nutritional advice. Part 2 covers protein malnutrition, eating disorders, osteoporosis, nutrient toxicity, cancer, inherited metabolic disorders, nutrient deficiency and diabetes mellitus. (Part I, outlining the clinical conditions and principles involved in nutritional diagnosis with a management approach to macrovascular disease and obesity, appeared in the October issue of Australian Family Physician.) PMID- 1445001 TI - Whiplash injury: misconceptions and remedies. AB - Misconceptions about whiplash injury and its common course are discussed. Different patient populations appear to suffer to varying degrees and social copying is evident in certain groups--features shared with the Australian 1983 to 1985 'epidemic' of 'repetitive strain syndrome'. Psychosocial factors and overtreatment delay recovery. Family physicians have the opportunity to properly assess and manage most patients. Wasteful therapy must be discouraged, and self care and patient responsibility encouraged. PMID- 1445002 TI - ST depression and review. PMID- 1445003 TI - An interpractice visit study. AB - In general terms the tests are performed to monitor disease or therapy, to help in reaching or excluding a diagnosis, and to screen for significantly treatable abnormalities in apparently healthy people either in the population at large (as in hyperlipidaemia) or in a specific risk group, for example, relatives of colorectal cancer sufferers. The result of the test gives some indication of its value in diagnosis. A preponderance of abnormal results suggest that it adds little to the clinical acumen of the observer, while in the opposite situation a high proportion of normal results suggest that it is being wrongly applied. Where the purpose is monitoring, the survey should throw some light on the value and frequency of use of the test. How often does the discerning general practitioner order routine electrolytes, serum digoxin levels, thyroid function tests? And, more significantly, how often should this be done? General practitioners are the appropriate people who can find out and establish an accepted standard. In screening it should be possible to demonstrate both the value of the test in terms of detection rate (ratio of normal to abnormal results) and the efforts of an individual practitioner in preventive medicine expressed as proportion of total work load. Suitably expanded it could be extended to discover the proportion of the total population at risk that is being reached by screening. This writer believes that general practice lacks a published body of knowledge culled from its collective experience on which it can call when challenged by colleagues, government or even hostile barristers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445004 TI - Acute otitis media. PMID- 1445005 TI - Easy bruising and bleeding. AB - The first steps in the identification of the cause of a bleeding disorder is careful evaluation of the patient's haemostatic competence and an assessment of the personal and family histories. Laboratory assessment should be guided by the clinical impression. PMID- 1445006 TI - Mini mental state examination. PMID- 1445007 TI - Slings (Part 1). PMID- 1445008 TI - Patient education. Footcare in diabetes. PMID- 1445009 TI - Hugh Carpenter. International general practitioner. AB - Hugh Carpenter's interests in general practice have been cosmopolitan and challenging. After seven years as a solo country general practitioner in Tasmania and then as State Director of the Family Medicine Programme in Tasmania, he was appointed to positions in China (1987-1990) and Moscow. His special interests are medical education and bilateral international medical relations, especially between China and Australia, and Great Britain with Russia, Bulgaria and Romania. PMID- 1445010 TI - A matter of chance. PMID- 1445011 TI - Glimpses of a cruel world. PMID- 1445012 TI - Assessing new drugs. PMID- 1445013 TI - Health care crisis in Africa. PMID- 1445014 TI - ANF in Japan. PMID- 1445015 TI - Nurse and the law. Informed consent and self-determination. PMID- 1445016 TI - The third age. A documentation model. PMID- 1445017 TI - Quality assurance and the Royal Australasian College of Physicians. PMID- 1445018 TI - Lipoprotein(a): a new independent risk factor for atherosclerosis. PMID- 1445019 TI - Lipoprotein(a) concentration in diabetes: relationship to proteinuria and diabetes control. AB - Diabetic patients are at increased risk of cardiovascular disease, particularly when proteinuria is present. Lipoprotein(a)[Lp(a)] levels were assessed in 37 patients with insulin dependent (IDDM) and in 75 patients with non-insulin dependent (NIDDM) diabetes who showed varying degrees of proteinuria and glycaemic control. Median Lp(a) in 112 diabetic patients was significantly greater than in 116 healthy controls (113 vs 48 mg/L; p less than 0.01). 86 of the patients had first morning urine albumin concentration less than 30 mg/L (normoalbuminuria = NA), 16 patients 30-200 mg/L (microalbuminuria = MA) and ten patients greater than 200 mg/L (albuminuria = ALB). There was no significant difference in median Lp(a) concentration between the three groups (NA = 108, MA = 163, ALB = 98 mg/L; p greater than 0.5). No significant difference in median Lp(a) or NIDDM treated with oral agents and/or diet (120, 98, 115 mg/L respectively; p greater than 0.7). When the 86 NA patients were divided on the basis of median fructosamine concentration (357 mumol/L), no significant difference was found in median Lp(a) levels between those grouped below or above this median (98 mg/L vs 118 mg/L; p greater than 0.5). Across all diabetics studied there was no significant correlation present between Lp(a) and urinary protein or glycaemic control. These cross-sectional results suggest that median Lp(a) concentration is increased in both IDDM and NIDDM patients, but this increase is not related to the degree of proteinuria or short-term glycaemic control. PMID- 1445020 TI - Semi-quantitative determination of microalbuminuria by urinary dipstick. AB - Microalbuminuria predicts subsequent clinical nephropathy and mortality in diabetic patients. This study was undertaken to determine the usefulness of a new immunochemical urinary dipstick test (Micral-Test, Boehringer Mannheim, GmbH Mannheim, Germany) in identifying urinary albumin concentrations within the microalbuminuric range (urinary albumin concentration 20-200 mg/L). Twenty-four hour urine specimens were collected from 298 consecutive diabetic outpatients. Micral-Test was performed by two laboratory scientists blinded to each other's results and those of radioimmunoassay (RIA) and immunoturbidimetry on the same specimen. When compared with RIA, Micral-Test had an overall sensitivity of 92.2%, specificity of 92.3% and positive predictive value of 86.4%. However, at the threshold value of 20 mg/1 Micral-Test showed false positive results in 37.8% of samples when compared with RIA. Similar results were obtained when Micral-Test was compared with immunoturbidimetry. We conclude that Micral-Test is a useful screening method for the detection of microalbuminuria. We suggest that positive tests be confirmed by a timed urine collection using established methodology and that patients whose Micral-Test is negative be subjected to annual retesting. PMID- 1445021 TI - The value of complement measurements in the assessment of lupus activity. AB - The complement system was studied prospectively in 29 patients, predominantly renal (25), with systemic lupus erythematosus (SLE) to examine the value of complement assays in the distinction between active and inactive disease. Disease activity was evaluated primarily by clinical, biochemical and histological parameters which were obtained at the time of assessment. Fourteen patients had active disease, as assessed by clinical and laboratory criteria. C1q, C4, C4a, C2, C3, C3a, C5, total haemolytic activity (CH50) and complement inhibitors were measured in each patient. The ratios of C4a:C4 and C3a:C3 were also calculated. Values for all components except C5 were different between control subjects and active patients while only CH50 was different between inactive patients and controls. All parameters except C4a:C4 and C5 were different between active and inactive patients. There was a highly significant difference in the number of active patients with reduced levels of C2, C3 and C3a:C3 compared to inactive patients (i.e. p less than 0.001) whereas lesser or no difference was observed for other parameters. The concentration of complement inhibitors was elevated in both groups. We conclude that, among readily available complement parameters, C2 and C3 provide the best assessment of disease activity in patients with SLE. PMID- 1445022 TI - Coronary artery disease in Asians. AB - From available studies, there appears to be a racial preponderance of coronary artery disease (CAD) among Indians when compared to other ethnic groups. We found that this racial difference exists even in a young Asian population with premature atherosclerosis. In this small series, these racial differences could not be explained by the commonly known risk factors for coronary artery disease- smoking, hypertension, diabetes and hypercholesterolaemia, findings similar to those found in older patients elsewhere. Only fasting triglyceride levels were significantly higher among young Indians compared to non Indians (p less than 0.02) although the importance of this finding as a risk factor for CAD remains controversial. The majority of these young patients were treated medically and their one year survival was good. PMID- 1445023 TI - The prevalence of asthma in Victorian adults. AB - To determine the prevalence of asthma in Victorian adults, we carried out a cross sectional postal survey utilising a new screening questionnaire which gathered data on self reported respiratory symptoms, whether asthma had been diagnosed and, if so, how it had been treated. Questionnaires were returned by 2198 (72%) of 3095 adults selected randomly from the Victorian electoral roll, an adequate response rate. The reported prevalences of individual asthmatic symptoms in the last 12 months ranged from 8% for nocturnal wheeze to 22% for current wheeze. Thirteen per cent of respondents had ever had asthma, 7% had experienced an attack within the last 12 months and 6% were currently taking medication. The high prevalence of asthma revealed by our study has major implications for the planning of health services. PMID- 1445024 TI - Reoperation for recurrent coronary artery disease--a ten year experience. AB - The need for reoperation caused by recurrence of coronary artery disease is becoming increasingly common. Although reoperation is more difficult and time consuming, with careful surgical technique it can be carried out with the same mortality as that described by many units for primary coronary artery bypass grafting (1.2-2.0%). In the 172 patients described here, who had coronary artery reoperations between 1981 and 1990, there were two in-hospital deaths (1.2%). There were three postoperative bleeds which required return to theatre. No patient suffered a postoperative neurological deficit or postoperative myocardial infarction. These reoperations comprised 6.9% of the 2497 coronary artery operations carried out in the same period. Follow-up disclosed eight late deaths, from five-62 months after operation; all survivors claim to be symptomatically improved. Consideration should be given to the potential problems of reoperation when carrying out primary myocardial revascularisation. PMID- 1445025 TI - Anabolic steroid abuse and toxicology. PMID- 1445026 TI - Does sulphinpyrazone reduce haemolysis from prosthetic heart valves? PMID- 1445027 TI - NSAID prescribing information. PMID- 1445028 TI - Diagnosing acute myocardial infarction. PMID- 1445029 TI - The use of the polymerase chain reaction in the identification of a high oxygen affinity haemoglobin--Hb Finlandia. PMID- 1445030 TI - RSI revisited. PMID- 1445031 TI - Australian and New Zealand Society of Nuclear Medicine, 23rd annual scientific meeting. Adelaide, South Australia, 3-6 May 1992. Abstracts. PMID- 1445032 TI - A mucosal barrier of gastric surfactant identified in the human stomach. AB - Using a special fixation procedure avoiding glutaraldehyde, an oligolamellar lining has been demonstrated by electronmicroscopy on the luminal surface of the human stomach and, with more lamellations, on the epithelial surfaces of oxyntic ducts and parietal cells. These results indicate that, in the human stomach, there is indeed a gastric mucosal barrier consisting of a multi-laminated structure of surface-active phospholipid (SAPL). This gastric surfactant is probably produced in parietal cells and surface mucus cells in which lamellar bodies and some prominent multi-focal lamellated agglomerates of SAPL were prevalent. These findings of a gastric mucosal barrier similar in structure and function to a very thin polyethylene liner are compatible with previous information about the hydrophobicity of the gastric mucosa, the clinical correlation of hydrophobicity with peptic ulceration and the action of barrier breakers (including Helicobacter pylori). It is speculated that the administration of exogenous gastric surfactant in various forms may be effective for inexpensive long-term maintenance of the ulcer patient treated acutely by more conventional means. PMID- 1445033 TI - Vitamin therapy for acute leukaemia. PMID- 1445034 TI - All-trans retinoic acid in the treatment of acute promyelocytic leukaemia. AB - All-trans-retinoic acid (ATRA) is known to induce differentiation of promyelocytes in vitro and also to induce remission of acute promyelocytic leukaemia in vivo. We treated 11 patients with poor prognosis acute promyelocytic leukaemia (APL) with ATRA and obtained seven complete and one partial remission. Remissions took one to three months to achieve and were associated with adverse effects including dry skin and bone pain. In eight patients the white cell count rose above 20 x 10(9)/L within the first ten days of retinoic acid treatment and this was associated with the development of pulmonary leukostasis in three patients which was fatal in one. Another two patients died of intracranial haemorrhage also within the first ten days. ATRA is a promising new agent in the induction therapy of this particular category of acute leukaemia. PMID- 1445035 TI - Neuroendocrine protein 7B2 in Prader-Willi syndrome. AB - 7B2 is a neuroendocrine polypeptide of unknown function, the gene for which is sited near or within the chromosomal region deleted in Prader-Willi syndrome and Angelman's syndrome. Plasma immunoreactive 7B2 levels were measured in 26 individuals with Prader-Willi syndrome, and appropriate controls. Plasma 7B2 levels were within normal limits compared to the control groups, in adults with Prader-Willi syndrome. 7B2 levels in children with Prader-Willi syndrome were higher, this age-dependent variation having been previously reported in normal children. PMID- 1445036 TI - Phrenic nerve pacing in two young quadriplegic ventilator-dependent patients. AB - Patients who survive high cervical injury are usually dependent on mechanical ventilation and tracheostomy if the lesion above C3 is complete. We report our experience with phrenic nerve pacing (PNP) to achieve ventilator-independence in two young quadriplegic patients. A diaphragm conditioning programme, and combination of low frequency electrophrenic stimulation within each inspiratory burst and low breathing frequency enabled both patients initially to achieve continuous 24 hour ventilation independent of mechanical ventilation. One patient reverted to overnight mechanical ventilation (six hours) after three years. PNP should be considered in ventilator dependent patients with high cervical injury to achieve independence and improve quality of life. PMID- 1445037 TI - Substantia nigra degeneration in motor neurone disease: a quantitative study. AB - There is increasing evidence of degeneration of nerve cells other than motor neurones in sporadic motor neurone disease (MND). Sporadic MND is occasionally associated with Parkinsonism. The aim of this study was to determine whether neuronal loss occurs in the substantia nigra of MND patients. Case records and pathological material from 14 patients with MND were reviewed. No patient had Parkinsonism documented. Sections of substantia nigra from the patients and 14 age/sex matched controls were analysed by neuronal and macrophage quantitation. The mean number of pigmented neurones at one standard level of substantia nigra was 863 in cases and 1094 in controls (p < 0.02); on average 21% (95% CI, 7-35%) fewer in the cases. The mean number of macrophages containing neuromelanin in cases was 106 and in controls 45 (p < 0.02). The results indicate that patients with MND have degeneration of the substantia nigra. Thus MND should be considered as a type of multiple system atrophy in which the motor neurone bears the brunt of the disease. The implication of this to the relationship between classical MND and MND with Parkinsonism-Dementia of the Western Pacific is discussed. PMID- 1445038 TI - Streptococcus pneumoniae: how common is penicillin resistance in Australia? AB - Streptococcus pneumoniae in the past were uniformly susceptible to penicillin. Increasing levels of resistance are now seen worldwide. To define the prevalence of this resistance in Australia, a collaborative study was carried out on all pneumococcal isolates at 15 large metropolitan teaching hospitals. During 1989 details of results of penicillin testing using routine methods were recorded. Isolates found resistant to penicillin were forwarded to Woden Valley Hospital for determination of penicillin minimum inhibitory concentration (MIC). All invasive isolates from five of these hospitals were also forwarded during 1989 and 1990 for MIC testing. Of the 1822 isolates tested, 31 (1.7%) were recorded as penicillin resistant. However, only 16 of 22 resistant isolates forwarded for MIC testing had MICs of > or = 0.1 mg/L confirmed. After adjustment to account for discrepancies with different laboratory testing methods we calculated the likely penicillin resistance to be 1% of isolates. Two of 105 invasive strains tested were found to be penicillin resistant. We conclude that penicillin-resistant S. pneumoniae isolates, including isolates from invasive sites, are found in Australia. All of these isolates had an MIC between 0.1 and 1 mg/L and are thus regarded as 'intermediately' penicillin resistant isolates. No high level resistance (MIC > or = 2 mg/L) was observed. Ongoing surveillance is essential to detect changes in resistance patterns and prevalence, as this will have implications for the empiric treatment of serious disease caused by S. pneumoniae. PMID- 1445039 TI - The practice of forensic medicine in Australasia: a review. PMID- 1445040 TI - Computerised management of an oral anticoagulant clinic. PMID- 1445041 TI - Alpha-1-antitrypsin replacement therapy--an early Australian experience. PMID- 1445042 TI - Ciprofloxacin associated bilateral achilles tendon rupture. PMID- 1445043 TI - Strychnine poisoning: an uncommon cause of convulsions. PMID- 1445044 TI - Asymptomatic primary hyperparathyroidism: the case for surgical management. PMID- 1445045 TI - IgG RF production in viral diseases. PMID- 1445046 TI - Intramedullary spinal cord sarcoidosis presenting with urinary retention. PMID- 1445047 TI - Safety of post-menopausal hormone replacement. PMID- 1445048 TI - Safety of post-menopausal hormone replacement. PMID- 1445049 TI - Safety of post-menopausal hormone replacement. PMID- 1445050 TI - Monoclonal gammopathy as a clue to the presence of thyroid lymphoma associated with auto-immune thyroiditis. PMID- 1445051 TI - Spongiotic (eczematous-type) dermatitis after inhaled budesonide. PMID- 1445052 TI - Fulminant viral hepatitis B in a small lymphocytic lymphoma patient. PMID- 1445053 TI - A survey of interhospital transfer of head-injured patients with inadequately treated life-threatening extracranial injuries. AB - A 12 month prospective study was undertaken to determine the frequency of untreated life-threatening extracranial injuries in patients transferred to a major trauma centre because of head injury. Of the 43 patients transferred (15 with isolated head injury and 28 with multiple injuries), four (9%) had an untreated life-threatening extracranial injury, which caused death in two. All four patients with untreated extracranial injuries were transferred from hospitals with general surgical staff and facilities. In three of the patients (none with a major head injury), the extracranial injuries were recognized at the referring hospital, but were left untreated in the rush to transfer the patient to a neurosurgical facility. In the fourth patient, who had a severe head injury, recurrent hypotension from a ruptured spleen was mistakenly ascribed to a scalp wound. The series shows that the dangerous practice of hurriedly transferring patients to trauma centres because of actual or perceived head injuries, while leaving major extracranial injuries untreated, continues despite warnings in the literature and the efforts of the Royal Australasian College of Surgeons through the Early Management of Severe Trauma programme. PMID- 1445054 TI - Controversies in the management of brainstem cavernous angioma: report of two cases. AB - Two cases of cavernous angioma involving the medulla oblongata are presented. Both cases underwent surgical excision with excellent outcome. The use of surgery via craniectomy is contrasted with stereotactic radiosurgery in light of the known natural history of the lesions. As a result, it is suggested that surgical excision provides immediate protection from the risks of recurrent haemorrhage, establishes a tissue diagnosis, allows complete removal at the primary intervention, avoids complications of radiation-induced damage and is performed more easily in these vascular anomalies due to the presence of a capsule with surrounding gliotic tissue. Additionally, it is implied that the natural history of lesions in this region is still unclear. For these reasons, it is suggested that surgical excision should be the primary therapeutic intervention for cavernous angiomata that involve the brainstem. PMID- 1445055 TI - Pars interarticularis stress and disc degeneration in cricket's potent strike force: the fast bowler. AB - Cricket fast bowlers are the potent strike force in a multidiscipline team. They subject their spines to repetitive sagittal plane and rotatory movements over many years. The effect of this repetitive stress has not previously been analysed. This study examined 20 former fast bowlers to determine the incidence of spondylolysis, spondylolisthesis and degenerative change. Fast bowlers are noted to have an increased incidence of spondylolysis. A mixed front/side bowling style involving more lumbar hyperextension or rotation has significant association with spondylolysis when compared with side-on bowling styles. There was a high incidence of radiological thoracolumbar degenerative facet joint and disc disease in former fast bowlers. PMID- 1445056 TI - Rehabilitation of lower limb amputees and some implications for surgical management. AB - Aspects of peri-operative management, amputation level and rehabilitation of the lower limb amputee are reported in the context of a review of a rehabilitation service for amputees which includes an integrated prosthetic service. Two hundred admissions were reviewed and some complex cases described. It is concluded that: a very close liaison between the surgeon and the rehabilitation team (ideally with preoperative consultation) is in the patient's best interests; any person previously walking (or a potential walker) should be considered for a trial of prosthetic walking; an integrated prosthetic service enhances the efficiency of the rehabilitation service; and that modification of the current Artificial Limb Scheme to allow manufacture of first definitive limbs in prosthetic rehabilitation units would further enhance service to patients. PMID- 1445057 TI - Splenic abscess. AB - Isolated splenic abscess is an uncommon condition. Seven cases seen between 1980 and 1990 are reviewed. The clinical presentation is non-specific and diagnosis is usually delayed. Computerized tomography allowed for accurate diagnosis in all cases. Pseudomonas species as a causative organism is reported to be rare, but were present in three of the present cases. Antibiotic therapy alone is insufficient and splenectomy remains the treatment of choice. PMID- 1445058 TI - Corporeal penile plication for correction of erectile penile deformity. AB - Penile curvature causing functional impairment of sexual intercourse is uncommon but a number of patients are significantly inconvenienced by this condition. Seven patients who had marked erectile deviation were treated with surgical plication for their penile deformity. Mean follow-up was 16 months (range 3-48 months) and no postoperative complications were encountered. In six cases the penis has remained straight. In one patient recurrence of deformity occurred 12 months after corporeal plication. The simplicity of the corporeal plication technique with the low incidence of associated complications makes it an attractive surgical alternative for the treatment of penile erectile deformity. PMID- 1445059 TI - Perineal proctectomy for rectal prolapse in elderly and debilitated patients. AB - This paper details the indications, operative technique and results of perineal proctectomy in the management of complete rectal prolapse in a high risk, elderly and debilitated group of patients. Eighteen procedures were performed by one surgeon (A.L.P.) on 16 consecutive patients over a 5 year period. Data collection was via: (i) retrospective analysis of hospital and office records; and (ii) response to a postal questionnaire by the patient, a relative or attending nursing staff. There were 14 females and two males with a mean age of 81 years. All patients had significant associated medical conditions. The interval from the time of a surgical procedure until review varied from 3 to 37 months with a mean follow-up period of 16 months. Total hospital stay varied between 6 and 20 days with a mean of 7 days. Eleven procedures were performed under general anaesthesia and seven under spinal anaesthesia. There was no postoperative mortality. One patient suffered an anastomotic haemorrhage that required operative intervention and another patient suffered a rectal stricture that necessitated dilatation. Two patients were re-operated for recurrent symptomatic prolapses at 34 and 36 months after the initial procedure. Continence improved in seven patients, worsened in one and was unchanged in the remaining patients. Fifteen of 16 patients were considered to have had a successful result from the operation with satisfactory control of the symptom of rectal prolapse. Perineal proctectomy is a low risk operative procedure for the elderly and debilitated group of patients in controlling complete rectal prolapse. If the condition recurs, the procedure can be repeated with equally low morbidity. PMID- 1445060 TI - Hurthle cell neoplasms of the thyroid gland revisited. AB - Hurthle cell tumours (benign and malignant) have been regarded as lesions with uncertain biological behaviour. However recent clinico-pathological studies have shown that they should be categorized as benign or malignant on the basis of capsular and/or vascular invasion, like other differentiated thyroid neoplasms. The fact that the tumours are composed of Hurthle cells is irrelevant. Currently, histological parameters do not seem to predict biological behaviour of Hurthle cell carcinomas. PMID- 1445061 TI - Vault prolapse: a new approach. PMID- 1445062 TI - The transanal resectoscope: an under-used instrument? AB - The use of the urological resectoscope in the treatment of rectal tumours has been described in detail. We report the use of the purpose built transanal resectoscope in the treatment of 34 patients. Fourteen patients had villous adenomas and all but one were relieved of symptoms. Of 20 patients with rectal carcinoma, three presented with acute intestinal obstruction and three had rectal stump recurrences. Palliation was excellent in patients with general symptoms, but the results were disappointing for rectal stump recurrences. Transanal resection (TAR) is a novel form of treatment for patients with rectal obstruction. Two patients in this study had their obstruction successfully relieved by transanal resection alone. This allowed formal bowel preparation and full pre-operative assessment. We feel that this technique is under-used and that the results of treatment justify more widespread acceptance of the procedure. PMID- 1445063 TI - A case of primary mesenteric fibromatosis. AB - A case of primary mesenteric fibromatosis is reported and the current modalities of therapy are discussed. Surgery is the primary mode of treatment. Other modalities should be reserved for gross local residual disease and for unresectable recurrence. PMID- 1445064 TI - Dieulafoy's ulcer: a palpable entity? AB - Two cases of Dieulafoy's ulcer are reported. Diagnosis was delayed but successful surgical treatment was achieved once the lesion was located by palpation. PMID- 1445065 TI - Delayed cerebrospinal fluid rhinorrhoea: a case report. AB - Post-traumatic cerebrospinal fluid (CSF) rhinorrhoea is a well recognized complication of closed head injury. Most cases occur soon after injury and a delay in presentation of more than 1 month is unusual. A case is reported of CSF rhinorrhoea presenting 15 years after initial trauma which was complicated by meningitis after 12 months. The management of this condition is reviewed. PMID- 1445066 TI - Central venous thrombophlebitis diagnosed by computerized tomography scanning. AB - A case is described in which computerized tomography scanning aided in a prompt diagnosis and assessment of an intravenous catheter-induced septic thrombus. Computerized tomography scanning detected gas bubbles within the thrombus, which extended from the right subclavian vein into the superior vena cava, and retrograde propagation of the thrombus into the right internal jugular vein. Computerized tomography scanning also helped in the assessment of the amount of deep tissue swelling present and the competence of the upper respiratory tract. PMID- 1445067 TI - Late complication of jejunal bypass: a case report. PMID- 1445068 TI - Spontaneous knotting of a pigtail ureteric stent in the ureter requiring percutaneous removal. AB - Insertion of a ureteric stent is a common procedure in urologic practice. Ureteric stenting may be performed for: ureteric obstruction, benign or malignant: to prevent ureteric obstruction from stone fragments after extracorporeal shockwave lithotripsy (ESWL); or to prevent leakage from the upper urinary tract. A case of spontaneous knotting of a ureteric stent in situ is reported. Although this complication has been reported previously it is rare. PMID- 1445069 TI - Ovine nasal zygomycosis caused by Conidiobolus incongruus. AB - About 700 sheep died on 52 farms in north-western New South Wales and south western Queensland over a 3 mo period. Affected animals had a marked asymmetrical swelling of the face, extending from the nostril to just anterior to the eyes. They lost condition rapidly and died within 7 to 10 days. At necropsy there was a unilateral severe necrogranulomatous rhinitis with extension of inflammation into the adjacent subcutaneous tissue, nasal septum and hard palate. Metastatic lesions were present in the draining lymph nodes and in the thorax. Histological changes consisted of a granulomatous reaction with numerous eosinophilic foci of necrosis and a diffuse, heavy, mixed inflammatory cell response. Many vessels had segmental necrosis and thrombosis. Fungal hyphae were numerous, particularly within or associated with necrotic foci. Conidiobolus incongruus was isolated from nasal tissues, parotid and submandibular lymph nodes and pulmonary lesions. PMID- 1445070 TI - A comparison of the pathogenicity of two strains of hog cholera virus. 1. Clinical and pathological studies. AB - The virulence of a strain of hog cholera virus isolated during an outbreak of mild disease in pigs in New South Wales in 1960/61 (the NSW strain) was compared over 11 days with that of a virulent strain by inoculating 8 pigs with each virus and comparing the ensuing clinical signs and pathology. Both viruses caused persistent pyrexia and leukopenia, the NSW strain 4 to 5 days and the virulent strain 3 days, after inoculation. Few other clinical signs were observed in the pigs inoculated with the NSW strain. In contrast, all pigs inoculated with the virulent strain became progressively depressed and incoordinated, and were killed between days 6 and 9. Bronchopneumonia and swollen, reddened lymph nodes were observed in pigs inoculated with both viruses. Few other gross lesions were observed with the NSW strain, but some pigs receiving the virulent strain had pustules in the tonsil and the anterior oesophagus, petechial haemorrhages in the kidney, and small infarcts at the margins of the spleen. There were marked differences in the histopathology, both in the variety of organs affected and the severity of lesions in individual organs. Suppurative bronchopneumonia occurred in both groups. Other changes in the pigs affected with the NSW strain were colitis, mild cerebral vasculitis, necrosis, haemorrhage and neutrophil infiltration in some lymph nodes and spleens. In pigs infected with virulent virus the cerebral vasculitis was so severe that there was necrosis of cells within the vessel walls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445071 TI - A comparison of the pathogenicity of two strains of hog cholera virus. 2. Virological studies. AB - Quantitative and qualitative differences were demonstrated in the amount of virus in a range of tissues from pigs infected with either the Weybridge or New South Wales (NSW) strains of hog cholera (HC) virus. The titre of the Weybridge strain in samples, as assessed by either virus titration in cell culture or by the density of specific fluorescing cells in tissue sections, was higher than that for the NSW strain. This correlated with the greater severity of the clinico pathological syndrome induced by the Weybridge strain. The implications of the differences in the virus content of tissues in the diagnosis of HC is discussed as is the use of monoclonal antibodies to differentiate HC and bovine virus diarrhoea viruses. PMID- 1445072 TI - Evaluation of an enzyme-linked immunosorbent assay for the detection of Mycoplasma hyopneumoniae antibody in porcine serum. AB - An enzyme-linked immunosorbent assay (ELISA) for detecting antibody to Mycoplasma hyopneumoniae in porcine serum is described. The results are presented as an ELISA ratio, calculated by dividing the absorbance of the test sample by the mean absorbance of control negative sera. In known infected pigs, the ELISA ratio was highest when the serum concentration applied to the ELISA plate was diluted 1 in 20 in PBS - Tween. Mean ELISA ratios ranged from 1.2 +/- 0.3 for pigs without porcine enzootic pneumonia (PEP) lesions to 5.5 +/- 1.5 for pigs observed with a PEP lesion reacting positively with immunofluorescent histopathology. Pigs observed with typical PEP lesions at slaughter, but not confirmed by immunofluorescent histopathology had a mean ELISA ratio of 4.9 +/- 1.7. The ELISA was highly sensitive (95.6%) and specific (98.8%) when pig sera from commercial piggeries of known M hyopneumoniae infection status were assessed. No cross reactivity with serum from a pig hyperimmunised with killed M flocculare was detected, and reactivity with serum from another pig hyperimmunised with killed M hyorhinis showed only weak cross-reactivity, which failed to reach the ELISA positive threshold (ELISA ratio 3) for M hyopneumoniae. PMID- 1445073 TI - Perennial ryegrass staggers in fallow deer (Dama dama). PMID- 1445074 TI - Complications of dystocia in a mare. PMID- 1445075 TI - An immunohistochemical study of plasma albumin extravasation in the brain of mice after the administration of Clostridium perfringens type D epsilon toxin. PMID- 1445076 TI - Bovine spongiform encephalopathy and Australia. PMID- 1445077 TI - Management of land and livestock contaminated with polychlorinated biphenyls. AB - Investigations were conducted on several small neighbouring beef cattle and sheep farms that were found to be contaminated with polychlorinated biphenyls (PCBs). The residues detected contained about 62% w/w chlorine and soil concentrations ranged from 0.35 to 1.9 mg/kg. Beef cattle and sheep grazing the contaminated land had PCB concentrations in their fat of 0.3 to 1.7 mg/kg and 0.19 to 0.45 mg/kg, respectively. The concentration of PCBs in the caudal fat of cattle was 0.3 to 2 times the concentration of PCBs in the land they were grazing and was positively related to stocking rates. PCBs were present in milk fat from cattle at about the same concentration as in caudal fat, and lactation appeared to contribute to decontamination. Wool grease from sheep contained about 1 to 2 times the concentration of PCBs in subcutaneous fat. Calves of contaminated cows also became contaminated. The half-life for decontamination of PCBs in a group of 8 young female beef cattle was calculated at 13 months. PCBs were detected in pasture samples at concentrations ranging from less than 0.01 mg/kg to 0.12 mg/kg. However, PCBs were not detected in any sample of hay cut from these paddocks. In 4 sheep fed a sole ration of this hay, traces of PCBs were detected in their fat following 89 days of feeding. Grazing livestock for meat production on land contaminated with PCBs is not recommended because livestock readily acquire residues, and PCBs persist in soil and livestock for long periods. Grazing sheep for wool production on land contaminated with PCBs may be an option. PMID- 1445078 TI - Failure of a single postpartum prostaglandin treatment to improve the reproductive performance of dairy cows. AB - A study was conducted to evaluate the effects of postpartum prostaglandin treatment on reproduction in 3 seasonal calving dairy herds. Recently calved lactating dairy cows were paired on herd, age, calving date and previous production index. One cow in each of the 196 pairs received a single intramuscular injection of 25 mg of the prostaglandin analogue, dinoprost, between 14 and 28 days after calving. Subsequent reproduction was monitored. Within each herd and overall, there was no significant effect of treatment on the intervals from calving to first service, mating start date to first service, calving to conception, mating start date to conception and first service to conception. Treatment also had no significant effect on 21-day submission and pregnancy rates, on the proportion of each group not pregnant at the end of mating, and on first service pregnancy rates. Responses to treatment did not vary between cows calving within 50 days of mating start date and earlier calving cows or between cows aged less than 5 years and older cows. PMID- 1445079 TI - Salivary and plasma cortisol as an index of stress in goats. AB - Total assayable cortisol in plasma was highly correlated (r = 0.97) with physiologically active free cortisol in plasma after routine management procedures in 1- to 3-weeks-old goats. Transport of adult goats caused significant increases (P less than 0.001) in free cortisol in saliva and in free and total cortisol in plasma. No difference (P greater than 0.05) between concentrations of free cortisol in saliva and in plasma was apparent before or after transport. The results demonstrated that the salivary cortisol method is a useful measure of stress in adult goats, and that the relationship between free and total cortisol in plasma, and the adrenocortical response to transport, appear to be similar in sheep and goats. PMID- 1445080 TI - Locomotor effects in sheep of alkaloids identified in Australian Tribulus terrestris. AB - Fresh, mature, ungrazed Tribulus terrestris plant material was subjected to a standard alkaloid extraction procedure. The extract was fractionated by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Two major alkaloid fractions were demonstrated. These fractions were identified by means of TLC, ultraviolet spectrofluorimetry (UVS) and HPLC, as the beta carboline indoleamines harmane and norharmane. The extractable alkaloid content was determined to be 44 mg/kg dry matter. Synthetic harmane and norharmane were administered subcutaneously to sheep at a dose rate of 54 mg/kg. Both compounds caused similar nervous effects. The main effect observed was limb paresis, which in some sheep was body side blased. The clinical signs observed in the experimental sheep were consistent with those described for naturally occurring cases of Tribulus terrestris staggers. It was proposed that harmane and norharmane accumulate in tryptamine-associated neurones of the central nervous system, during months of tribulus ingestion, and gradually interact irreversibly with a specific neuronal gene DNA sequence. PMID- 1445081 TI - Mechanisms underlying Phalaris aquatica "sudden death" syndrome in sheep. AB - Twenty outbreaks of Phalaris aquatica "sudden death" syndrome in sheep were investigated between 1981 and 1991. Four were confirmed and one was suspected, to be a cardiac disorder; 5 were confirmed and 3 were suspected, to be a polioencephalomalacic disorder; the aetiology of the remaining 7 outbreaks could not be determined. Potentially toxic levels of hydrocyanic acid (20 to 36 mg/100 g) were measured in the 3 toxic phalaris pastures tested. The measurement of potentially toxic levels of nitrate nitrogen (2920 micrograms/g) in toxic phalaris pastures by others, was noted. It is suggested that phalaris "sudden death" syndrome could have as many as 4 different underlying mechanisms, and that these might reflect the presence in the plant of a cardio-respiratory toxin, a thiaminase and amine co-substate, cyanogenic compounds, and nitrate compounds. PMID- 1445082 TI - Serological response of vaccinated sheep after challenge with Corynebacterium pseudotuberculosis. PMID- 1445084 TI - Spongiform encephalopathy in an imported cheetah (Acinonyx jubatus). PMID- 1445083 TI - Angiostrongylosis in dogs in Sydney. PMID- 1445085 TI - Lupinosis in yearling cattle. PMID- 1445086 TI - Bovine cranial zygomycosis caused by Saksenaea vasiformis. PMID- 1445087 TI - Occupational contact dermatitis in New South Wales. AB - Five hundred and seventy patients with occupational contact dermatitis (OCD) were seen between 1984 and 1990 at the Skin and Cancer Foundation in Sydney. Data derived from these patients demonstrated that hairdressing, food, construction and the medical industries were the most at risk of OCD. The hairdressing and food industries had a high percentage of apprentices suffering OCD whilst the 35 to 44 year age bracket was most at risk in the construction industry. Allergic contact dermatitis was responsible for 38.2% of cases. The main allergens were chromate, thiuram, epoxy resin, nickel and cobalt. A third (33.9%) of patients were atopic. The average time lost from work was 16 days each year and the calculated yearly cost of OCD in New South Wales was approximately $12 million. PMID- 1445088 TI - Skin reactions to diltiazem. AB - A survey of Australian dermatologists was conducted into skin reactions observed to diltiazem. These have included: erythema multiforme, subcorneal pustular dermatosis, photosensitive erythroderma, macular exanthem, allergic vasculitis and urticarial vasculitis. The range of clinical and histopathological features are described. A review of the literature is presented. Photosensitive erythroderma and urticarial vasculitis have not, to our knowledge, been reported in the literature previously. PMID- 1445089 TI - Keratoderma hereditaria mutilans. Etretinate treatment and electron microscope studies. AB - Keratoderma hereditaria mutilans is a rare inherited cornification disorder characterized by hyperkeratosis of palms and soles with a characteristic "honey comb" appearance, keratotic constriction furrows of one or more digits (pseudo ainhum) and threatening spontaneous amputation. Approximately 30 cases have been reported, but the ultrastructural features have not been well characterized. In this article, we describe the clinical, histologic, and ultrastructural findings in our patient. A biopsy specimen taken before treatment with etretinate showed hyperkeratosis with a well-preserved granular layer and acanthosis. Ultrastructural examination disclosed that the spinous cells and granular cells contained marked swollen mitochondria, many desmosomes, and that corneocytes contained many membrane coating granules (MCG) and lipid like vacuoles. After initiation of treatment, considerable clinical improvement was observed, but without significant histologic modification. The principal post-treatment ultrastructural changes were the reduction of mitochondrial swelling in spinous and granular cells and the reduction in the number of MCG in corneocytes. The intercellular spaces showed increased amounts of fine and coarse granular substances. Stimulation of Langerhans cells was observed. Marginal band formation occurred normally after treatment. PMID- 1445090 TI - Familial non-diabetic necrobiosis lipoidica. AB - Necrobiosis lipoidica (NL) is a cutaneous disorder with distinctive clinical and morphologic characteristics. It is associated with diabetes mellitus in two thirds of cases. The aetiology and pathogenesis of NL are unknown but familial cases of NL seem to be extremely rare. We report the occurrence of NL in two sisters with normal glucose tolerance. PMID- 1445091 TI - Hormonally exacerbated hereditary angioedema. AB - Hereditary angioedema is a rare disorder which is associated with an inherited deficiency of the inhibitor of the activated first component of complement. Genetic transmission occurs in an autosomal dominant manner. Affected patients are heterozygotes, and their deficiency is incomplete, many of them having up to 20% of the normal amount of the inhibitor. We describe two cases of C1 esterase inhibitor deficiency occurring in a mother and daughter in whom the symptoms appeared to be related to the menstrual cycle or the taking of the oral contraceptive pill. Although both features have been mentioned in the literature, to the best of our knowledge premenstrual exacerbations have not been documented previously. We examined the likely basis of hormonally exacerbated hereditary angioedema. PMID- 1445092 TI - Pilomatrix carcinoma of the scalp. AB - A matrical carcinoma (pilomatrix carcinoma) of the scalp is described--the first reported case in this site. This malignant hair follicle tumour must be distinguished histologically from benign pilomatricoma and proliferating trichilemmal tumour, which can have similar features. PMID- 1445093 TI - Infantile pyoderma gangrenosum. AB - A six month old female infant with pyoderma gangrenosum is reported. Pyoderma gangrenosum in an infant is rare. The child responded to pulse therapy with intravenous dexamethasone and intralesional triamcinolone acetonide. PMID- 1445094 TI - Superficial mycoses in Saudi Arabia. AB - Between June 1988 and December 1990, 1018 cases of superficial mycoses were investigated. Diagnosis was confirmed by microscopic examination in 503 cases and the causal agent was isolated in 490 cases. Tinea capitis accounted for 47.7% (92.5% in children below 10 years of age). The frequency of other clinical types in descending order was pityriasis versicolor 25.8%, tinea corporis 9%, onychomycosis 5.8%, tinea pedis 4%, intertrigo 3.9% and tinea cruris 2.8%. Erythrasma was encountered three times and mixed piedra and trichomycosis axillaris once. Microsporum canis was the commonest aetiological agent, responsible for 46.9% of ringworm infections. Malassezia furfur was the next most common agent (26.5%) followed by Candida albicans (8.6%) and Trichophyton violaceum (8.2%). Other species were found less frequently. T.simii was isolated from four cases of tinea cruris and one each of tinea capitis and tinea corporis, and Piedraia hortae and Trichosporon beigelii from a case of mixed piedra infection. PMID- 1445095 TI - Occupational skin disease. Skin and Cancer Foundation: 4th April 1992. PMID- 1445096 TI - Dermatology 2000--facing the challenges. Canberra, 24-27 October 1991. PMID- 1445097 TI - Management of venous ulcers. PMID- 1445098 TI - Psoriasis, chronic benign familial pemphigus, and dysplastic naevus syndrome in a family. PMID- 1445099 TI - A peculiar pruriginous dermatoses with gross reticular pigmentation. PMID- 1445100 TI - A comparison between M.R.I. and C.T. in acute spinal trauma. AB - Magnetic Resonance Imaging (MRI) at 0.3T and Computed Tomography (CT) were compared in the retrospective evaluation of 34 patients with acute spinal cord injury. MRI was highly accurate in the imaging of vertebral body fracture, and spondylitic changes, and is the method of choice for imaging ligament injury, traumatic disc protrusion and spinal cord compression. It was also useful for the identification of subtle subluxations in the sagittal plane. CT remains the method of choice for imaging neural arch fractures. MRI at 0.3T is a valid technique for assessing patients with acute spinal trauma. PMID- 1445101 TI - A comparison between M.R.I. and C.T. in the investigation of neurological deterioration in longstanding spinal trauma. AB - MRI at 0.3T and CT with myelographic contrast (CTM) were compared in the retrospective evaluation of 35 patients investigated for the development of new neurological symptoms following longstanding spinal cord injury. Compared with MRI, CTM was relatively accurate for the demonstration of spinal cord compression, but failed to identify 23% of patients with spinal cord atrophy, and 43% of patients with post-traumatic syrinx formation. However, 5 patients had unsatisfactory MR imaging, either due to motion or metallic artifact, and in 3 of these, CTM demonstrated a syrinx. Although MRI is the method of choice in the investigation of this problem, CTM may still be required for patients with an unsatisfactory MR examination. Magnetic Resonance (MR) imaging is now an established technique for imaging the spine, with accurate depiction of the spinal cord, as well as the adjacent soft tissues (1, 2). However, the cost of this technique, and its as yet limited availability in Australasia, has resulted in the necessity to demonstrate its superiority over other imaging modalities for any specific clinical problem (3). One of the major areas of impact of MR has been in the investigation of the problem of acute neurological deterioration in patients with past spinal trauma (4, 5, 6). Some of these patients will have treatable causes of deterioration, either a post-traumatic syrinx, or spinal cord compression (6), and MR can be used to image these conditions (7), which, until recently, were investigated with computed tomography with myelographic contrast medium (CTM), (8, 9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445102 TI - Cardiovascular evaluation in Turner syndrome: utility of MR imaging. AB - Forty patients with karyotypically proven Turner syndrome were prospectively studied using magnetic resonance imaging (MRI) and echocardiography in order to determine the frequency of cardiovascular anomalies and to assess the utility of both imaging modalities as methods for cardiovascular evaluation in Turner syndrome. Cardiovascular anomalies were found in 45% of patients. A high absolute prevalence of bicuspid aortic valve (17.5%) and aortic coarctation (12.5%) were observed relative to comparable series. Of clinically significant abnormalities, three of five aortic coarctations and four of five ascending aortic dilatations were solely MRI detected and not evident at echocardiographic examination. MRI is thus seen as a valuable adjunct to echocardiography in the cardiovascular evaluation of Turner syndrome patients. The usefulness of MRI primarily relates to its ability to provide excellent visualisation of the entire thoracic aorta where a large proportion of clinically significant anomalies occur in Turner syndrome. PMID- 1445103 TI - Liver CT: a practical approach to dynamic contrast enhancement. AB - The aim of this study was to establish a practical, simple protocol that reliably produces high quality dynamic incremental computed tomography (CT) of the liver. We reviewed 90 patients randomly allocated into six different protocols. All had preliminary unenhanced scans followed by a dynamic incremental CT of the liver. An initial delay of 30 seconds was used from the commencement of the injection of Iopamiro 370. The groups were: 1. Pump infusion (a) 100 mls at 2 mls/sec scanning inferosuperiorly. (b) 100 mls at 2 mls/sec scanning superoinferiorly. (c) 100 mls at 1 ml/sec scanning inferosuperiorly. (d) 50 mls at 1 ml/sec scanning inferosuperiorly. 2. 40 mls hand injected bolus followed immediately by 60 ml pump infusion at 1.3 mls/sec scanning inferosuperiorly. 3. 50 mls hand injected bolus scanning inferosuperiorly. The parameters recorded were the degree of hepatic parenchymal and hepatic venous enhancement and the aortic--IVC difference at the last slice through the liver, all measured in Hounsfield units. The protocols using 100 mls of contrast produced approximately twice the parenchymal and hepatic venous enhancement compared with those using 50 mls. Approximately 60 90% of examinations using 100 mls produced scans through the entire liver during the bolus or nonequilibrium phase, deemed the most sensitive for the detection of focal lesions, compared with 13-33% of those using 50 mls. Equally satisfactory results were obtained using the relatively inexpensive Biotel power injector preceded by a 40 ml hand injected bolus, compared with using an Angiomat angiography infusion pump.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445104 TI - The perivertebral collar--a new sign in lymphoproliferative malignancies. AB - Nine patients with lymphoproliferative malignancies, one of whom had not been previously diagnosed, were found on CT examination for back pain to have partial or complete soft tissue perivertebral collars. The thoracic and or lumbar regions were involved in all. Only 3 had gross bony changes at the time, and in others the changes appeared so innocuous that in combination with the vague clinical symptoms their significance was underestimated. Five patients ultimately had episodes of cord compression, and in all nine the appearance of this spinal lesion appeared to be of grave prognostic significance. All 9 were dead within 1 year of the presentation of their spinal lesions. The observation of a perivertebral collar in the context of a known or suspected lymphoproliferative malignancy should therefore raise the strong suspicion of spinal involvement. The vertebrae should be examined on bone windows and the contents of the spinal canal on narrow windows to assess bony and epidural spread. PMID- 1445105 TI - Pulmonary arteriovenous malformations: pathology, clinical features and treatment with balloon and coil occlusion. AB - This paper discusses the cases of 5 patients who have had therapeutic occlusion of their pulmonary arteriovenous malformations (PAVM) performed radiologically at Alfred Hospital in the past 4 years. The salient pathological, clinical and radiological features of PAVM are also presented. PMID- 1445107 TI - An evaluation of the effect of processing conditions on mammographic film contrast, fog levels and speed. AB - While it is well established that extended development times and temperatures will increase mammographic film contrast and speed (1), little work has been done to date in extending this work to encompass all common screen-film types and to study the effect of processing chemistry variations on contrast speed results. This paper reports on four locally available mammographic films which, after exposure in conditions that closely simulate clinical conditions, have been developed with four different development chemicals as a function of development temperature and time. Three development times were used (23, 32 and 42 seconds) in combination with four development temperatures (32, 34, 36 and 38 degrees). The results support the previously published result of increased speed and contrast with extending development time and temperature. It was further found that, for some film types, the film contrast varied significantly over film density when developed with extended processing. Other film types, however, maintained high contrasts over large film density ranges. In some cases the increased contrast was accompanied by elevated film fog levels. The development of mammographic films in non recommended chemistries produced varying results, mostly detrimental, which demonstrated that selection of development chemistry as well as optimal development times and temperatures, is critical for good film performance. PMID- 1445106 TI - Accelerated thrombolysis facilitated by direct puncture of occluded prosthetic femoral grafts. AB - Inability to access occluded grafts is a major limitation to successful thrombolysis and may even preclude it. This paper addresses the problem and offers a new technique of direct puncture of prosthetic grafts through which thrombolysis and angioplasty can be performed. These techniques resulted in accelerated thrombolysis in all 15 patients studied with no failures due to inability to attain graft access. PMID- 1445108 TI - Cleido-cranial dysostosis--skeletal abnormalities. PMID- 1445109 TI - Iodine-125 irradiation of choroidal melanoma: clinical experience from the Prince of Wales and Sydney Eye Hospitals. AB - We examined the records of 53 patients treated for choroidal melanoma between 1985 and 1989. The aim of this study was to assess the safety and short-term results of iodine-125 episcleral plaque therapy. There were 28 males and 25 females, aged 20 to 77 years (median 61 years), treated for single tumours with a median diameter of 9 mm (range 5 to 15 mm) and with a median thickness of 4 mm (range 2 to 10 mm). The plaques containing iodine-125 seeds were chosen according to tumour size: 10 mm (16 patients); 15 mm (36 patients); 20 mm (one patient). All patients are alive at last follow-up (median 1.3 years, range 4 months to 3.3 years). Four patients underwent enucleation for melanoma progression. Thirty patients have developed some type of complication (more than one complication occurred in the same eye in 12 patients): retinitis (19), optic neuropathy (7); cataract (4), rubeosis iridis (2). Overall, visual acuity deteriorated in 32 patients, remained stable in 12 patients and improved in 9 patients. Iodine-125 plaque therapy appears to offer patients good prospects of tumour control and preservation of useful vision. PMID- 1445110 TI - Primary squamous cell carcinoma of the breast. AB - A patient with pure primary squamous cell carcinoma (SCC) of the breast is reported. The patient was a 72 year old female who presented with a 4 month history of an enlarging left breast mass. Surgery involved a radical mastectomy and this was followed by post-operative radiotherapy and chemotherapy. The patient died of extensive metastatic disease some four months after surgery. The various characteristics of SCC of the breast are briefly discussed. A sub-group of SCC of the breast is identified among reported cases in which the clinical course is characterised by a very rapid growth, extremely aggressive behaviour and early metastasis. PMID- 1445111 TI - Percutaneous drainage of a thigh haematoma: case report of an unusual radiographic appearance. AB - We present a case of fat necrosis in the thigh of a ten year old girl, resulting in unusual multiple, ovoid filling defects seen in the residual cavity following drainage of a subcutaneous haematoma. No similar cases have been found on review of the literature. The appearance is described to aid diagnosis at the time of initial cavity drainage, avoiding the need for further investigation. PMID- 1445112 TI - Multifocal metachronous osteogenic sarcoma. PMID- 1445113 TI - Bilateral spondylolysis and associated dysplasia of C6. AB - Cervical spondylolysis is a rare condition, characterised by the presence of a corticated cleft between the superior and inferior articular facets of the articular mass (1). This defect involves the cervical equivalent of the pars interarticularis of the lumbar spine. Associated dysplastic changes are present, suggesting that the lesion is congenital (1 and 2). This case report describes bilateral spondylolysis and associated dysplasia of C6 in an 18 year old female. The importance of this lesion lies in its differentiation from the more serious articular mass fracture or dislocation (1). PMID- 1445114 TI - Post-laminectomy pseudomeningocele: an unusual cause of bone erosion. AB - Pseudomeningocele is a rare complication of laminectomy, which can cause recurrent back pain with or without radicular signs. A case of bone erosion of the posterior vertebral elements by a pseudomeningocele is discussed. PMID- 1445115 TI - Sonographic appearance of plasmacytoma of the testis. AB - A case of solitary extramedullary plasmacytoma of the testis is presented demonstrating the appearances on ultrasound. The clinical implications of this diagnosis are discussed. PMID- 1445116 TI - Scintigraphic diagnosis and computed tomographic localization of an accessory spleen following relapse of chronic immune thrombocytopaenia. AB - Chronic immune thrombocytopaenia is an immunologically mediated disorder resulting in disordered platelet kinetics and potentially life-threatening thrombocytopaenia. Failure of medical therapy is an indication for splenectomy, and responses are seen in 80% of patients following this procedure. An important cause of relapse following splenectomy is the presence of an accessory spleen. We describe a patient with Hodgkin's Disease who developed chronic immune thrombocytopaenia despite previous splenectomy. A remission was induced with immunosuppressive therapy, but he later relapsed. An accessory spleen was detected using 99mTc denatured red blood cells and localized using computed tomography (CT). Resection of the accessory spleen resulted in clinical remission. Accessory spleens are often small in size. Combined modality imaging is recommended in the evaluation of patients with a possible accessory spleen. PMID- 1445117 TI - Intrathoracic right kidney diagnosed by ultrasound. AB - Intrathoracic kidneys are rare. A case is described in which the initial intravenous urogram performed for prostatism appeared to show a non-functioning right kidney. A subsequent ultrasound examination revealed that the right kidney was situated in the right hemithorax, well above the liver. Pelvic ectopic kidneys are common and standard teaching is to perform a full length film should an immediate or 5 minute renal area radiograph suggest an absent/non-functioning kidney. With the increasing use of ultrasound in the initial assessment of patients with prostatism, the possible intrathoracic location of a kidney should be remembered when there is failure to demonstrate a kidney in the abdomen or pelvis. PMID- 1445118 TI - How should a waiting list for treatment be managed? PMID- 1445119 TI - The editor's back. PMID- 1445120 TI - Editor's case quiz (3). Cholecystoduodenal fistula. PMID- 1445121 TI - Maternal mortality in Australia. PMID- 1445122 TI - Jaundice: clinical practice in 88,000 liveborn infants. AB - We reviewed jaundiced infants born between 1971 and 1989. Jaundice was diagnosed in infants whose serum bilirubin level was found to be 154 umol/l or greater. Of 88,137 livebirths, 10,944 (12.4%) were jaundiced. The most common aetiological factor was prematurity (20.3%), followed by ABO erythroblastosis (5.5%), sepsis (1.8%), Rh erythroblastosis (1.8%), bruising (1.3%), multifactorial (1.0%) and glucose-6-phosphate dehydrogenase deficiency (0.5%). In the remainder (67.8%) no cause was found or inadequate investigations were performed to determine a cause. During the period under review there was a significant increase (r = 0.91) in the proportion of newborn infants with jaundice of prematurity, in those not investigated (r = 0.92) and a decrease in the proportion with bruising (r = 0.90) as the cause. Phototherapy was used on 4,126 (37.7%) infants and exchange transfusion performed on 248 (2.3%). Causes of jaundice in infants requiring exchange transfusion were Rh erythroblastosis (108, 43.6%), ABO erythroblastosis (58, 23.4%), jaundice of prematurity (44, 17.7%) and a variety of causes in the remaining 38 (15.3%). Death occurred in 164 (1.5%) infants. In only 7 (4.3%), however, was the death possibly related to hyperbilirubinaemia or its treatment (Rh erythroblastosis (4), necrotizing enterocolitis following exchange transfusion (2) and pulmonary haemorrhage following exchange transfusion (1)). Phototherapy proved safe with no deaths attributable to its use. PMID- 1445123 TI - Is there a lower limit for birth-weight/gestational age and antenatal steroid therapy? AB - The aim of this study was to determine if there is a lower limit for birth weight/gestational age below which antenatal steroid therapy may not improve fetal survival. The association between antenatal steroid therapy and survival to 2 years of age was assessed in 2 cohorts of children of birth-weight below 800 g or of gestational ages below 27 weeks. Antenatal steroid therapy was associated with significantly higher survival rates in infants of birth-weight 500-599 g and 700-799 g, and at gestational ages of 25 and 26 weeks. There were few survivors before 25 weeks and none below 500 g birth-weight. After adjustment for extraneous prognostic variables, antenatal steroid therapy was associated overall with approximately a doubling of the survival rates of infants of birth-weight 500-799 g, and of gestational ages 24-26 weeks. In the absence of maternal contraindications, if the goal is to deliver a surviving infant, this study suggests that the obstetrician may assist the survival chances of the tiniest and most immature infants by treating the mother with steroids before birth, with no apparent lower limit of birth-weight or gestational age. PMID- 1445124 TI - Clinical versus ultrasound estimation of fetal weight. AB - A prospective study was carried out on 50 patients who had their fetal weight estimated by 3 clinicians of different seniority and compared to the ultrasound estimated fetal weights using 3 different formulas. All the patients delivered within 24 hours of their clinical and ultrasound estimates. A wide range of birth weights (1,800-4,500 g) was estimated among the 3 different races (Malay, Chinese and Indians). The results showed that there was no significant difference in birth-weight estimation amongst the 3 clinicians as well as between the 3 ultrasound formulas used. There was however significant difference between these 2 groups when compared with the actual birthweight with clinical estimation being superior to ultrasound estimation in our population. This level of significance did not extend beyond 4,000 g fetal weight (actual) thus making both clinical and ultrasound estimation of fetal weight equally accurate after 4,000 g. This has important implications for developing countries where there is a lack of technologically advanced ultrasound machines capable of doing sophisticated functions like fetal weight estimations but has experienced clinicians who could perform this function equally well if not better. PMID- 1445125 TI - An assessment of key aetiological factors associated with preterm birth and perinatal mortality. AB - The 4 main causes of preterm births in 303 women with consecutive deliveries in Flinders Medical Centre were premature rupture of the membranes (39%), spontaneous preterm labour (22%), pregnancy-induced hypertension (17%) and antepartum haemorrhage (12%). Premature rupture of the membranes occurred with equal frequency in singleton and multiple pregnancies and there was no difference in the frequency of this cause between the pregnancies with live outcomes and those with perinatal deaths. Spontaneous preterm labour was more common in multiple pregnancies (39%) than in singleton pregnancies (22%). One in 3 of the preterm births and 79% of the pregnancies with perinatal deaths occurred at less than 32 weeks' gestation. As it is unlikely that any single obstetric and social intervention will be able to reduce these causes of preterm birth research must continue to find markers to predict premature rupture of the membranes and spontaneous preterm labour. PMID- 1445126 TI - Rates of caesarean section and neonatal mortality. AB - A comparison of the yearly statistics of National Maternity Hospital (Dublin) and University Hospital (Newark) was undertaken for the years 1983-1989. The findings appear to indicate that after the elimination of major confounding factors, the substantially higher rates of Caesarean section in Newark (17.5% versus 5.8%) did not bring about a measurable reduction in the rate of neonatal losses. The impact of paediatric care upon the respective neonatal outcomes could not be assessed on the ground of the reviewed data. PMID- 1445127 TI - The influence of maternal age on cesarean section rates. AB - Caesarean section rates have risen in recent years and this has led to concern. Significantly different Caesarean section rates have been reported between different teaching hospitals. This study compares the Caesarean section rates between 2 Sydney teaching hospitals draining populations from different areas of Sydney. Raw figures showed significantly different Caesarean section rates (22.5% at Royal North Shore Hospital compared with 18.3% at Westmead Hospital). Each hospital has a significantly different case mix when maternal ages are compared. When Caesarean section rates were corrected for maternal age and parity, there was no significant difference. As maternal age is an important factor influencing Caesarean section rates, future reports on obstetric services should consider this factor in making comparisons. PMID- 1445128 TI - Symptoms and signs with scar rupture--value of uterine activity measurements. AB - To evaluate the symptoms and signs of scar rupture with special reference to intrauterine pressure measurement a retrospective analysis of labour records of those women who had trial of labour with a previous Caesarean scar in the National University Hospital over a period of 6 years (1985-1990) was carried out. Known symptoms and signs associated with scar rupture, cardiotocographic tracings and fetal and maternal outcome in these patients were studied. Of the 1,018 women with previous Caesarean scar (4.2% of our pregnant population at term) 722 (70.9%) had trial of labour; 70% delivered vaginally. There were 4 (0.55%) incomplete and 5 (0.69%) complete scar ruptures. All 9 women had an oxytocin infusion; 3 were diagnosed postdelivery (all 3 had complete ruptures); 3 of the 6 who had rupture prior to delivery had sudden reduction in uterine activity, 1 had scar pain and prolonged bradycardia and 2 had no symptoms or signs. Continuous cardiotocography with intrauterine pressure measurements may help to identify scar rupture early and may be of value especially in those who have an oxytocin infusion. PMID- 1445129 TI - Vaginal delivery after caesarean section. AB - In a prospective study of 318 consecutive pregnancies complicated by previous Caesarean section, 193 (61%) had an elective repeat Caesarean section, 125 (39%) had a trial of labour and 80 (64%) of these women achieved a vaginal delivery. The incidence of uterine rupture was 0.8% (1 of 125). The vaginal delivery rate was not influenced by the indication for the first Caesarean section (including cephalopelvic disproportion), birth-weight, health insurance status, use of epidural analgesia or oxytocin in labour. Perinatal morbidity was unaffected by the mode of delivery and maternal morbidity was comparable following elective and emergency repeat Caesarean section. Patients having a vaginal deliver spent significantly less time in hospital. We conclude that vaginal delivery after lower segment Caesarean section is safe and should be considered in most patients after a critical review of the indication for the first Caesarean section. PMID- 1445130 TI - Narcotic addiction in pregnancy with adverse maternal and perinatal outcome. AB - A retrospective case controlled study was carried out on 51 Chinese gravidas who had abused narcotics and who were delivered in a teaching hospital in Hong Kong. Heroin was the most commonly abused drug. The number of patients who changed from heroin to methadone was small. The major antenatal complications were late antenatal booking (average 28 weeks), prematurity (41%), small for gestational age baby (27.5%), antepartum haemorrhage (13.7%) and high prevalence of venereal disease (23.5%). The babies born to drug addicted mothers were on average 629 g lighter at birth, 5 cm smaller in head circumference and 7 cm shorter in body length. Neonatal withdrawal symptoms occurred in 83% of all drug exposed neonates. The perinatal mortality rate was 19.6 per 1,000 total birth which was 2.5 times that of the control group. There was one maternal death in our series. Drug addiction in pregnancy poses a major risk to both mother and child. PMID- 1445131 TI - Intrapartum fetal stimulation testing. AB - Intrapartum vibroacoustic stimulation testing (VAST) had a sensitivity of 100%, a specificity of 59.6% and a positive predictive value of 27.6% for the detection of fetal acidosis in this study of 60 cases. The use of VAST could significantly reduce the requirement for fetal capillary blood sampling. However, fetal scalp stimulation (FSS) was found to be an unreliable test to exclude fetal acidosis. PMID- 1445132 TI - Doppler ultrasound in pregnancies with hypertension. AB - Doppler studies of the arcuate and umbilical arteries were performed longitudinally commencing at 24 weeks or less, in 29 pregnant women with chronic hypertension. The hypothesis was that pregnant women with chronic hypertension who develop superimposed gestational proteinuric hypertension and/or deliver small for gestational age babies are those who have abnormal arcuate and/or umbilical flow velocity waveforms. Abnormal arcuate waveforms occurred in 7 women and abnormal umbilical waveforms in 12. Nine babies were small for gestational age, and 6 of them had abnormal arcuate waveforms. Abnormal arcuate waveforms were significantly associated with the delivery of a small for gestational age baby (p = .001) and identified those babies where early delivery was necessary for fetal reasons. All small for gestational age babies had abnormal umbilical waveforms. Superadded gestational proteinuria (or preeclampsia) occurred in 8 pregnancies, however, only 3 had abnormal arcuate waveforms. An abnormal arcuate waveform did not predict the later development of gestational proteinuria. An abnormal umbilical waveform however, was associated with the subsequent development of gestational proteinuria. We consider that these findings need to be confirmed in a larger study. PMID- 1445133 TI - The effect of consanguinity on pregnancy-induced hypertension. AB - The aetiology of pregnancy induced hypertension (PIH) is unknown. Either an immunological or a genetic disorder are considered likely, with possibly an interaction between the two. If this were true, homozygosity would play an important role. Though consanguinity is believed to play a protective role, the effect of inbreeding on PIH has been inadequately studied. In South India consanguinity is common (26%). We prospectively studied 814 primigravidas of whom 213 had consanguineous marriages. The proportion of women who developed PIH was compared in the 2 groups of women with consanguineous and nonconsanguineous marriages. The odds of a patient with PIH being consanguineous was 1.12 with a 95% confidence interval of 0.72-1.75. Our observations suggest that consanguinity does not influence the incidence of PIH. PMID- 1445134 TI - Norethisterone and gestational diabetes. AB - In a single practice during the 21 years 1971-1991, the incidence of gestational diabetes in pregnancies in which norethisterone was prescribed was 32.4% (22 of 69) in comparison with 7.1% in pregnancies in which the women did not take norethisterone (137 of 1,684) (p < 0.001). Gestational diabetes was no less severe (degree of hyperglycaemia, need for insulin therapy) when associated with norethisterone. However, follow-up revealed that gestational diabetes when associated with norethisterone had a lesser risk of emerging diabetes mellitus and impaired glucose tolerance. Masculinization of a female fetus occurred in 5 of 39 (12.8%) exposed to norethisterone; all were cases of clitoral hypertrophy not requiring surgical treatment. Norethisterone in these 69 pregnancies accounted for 33.3% (5 of 15) cases of clitoral hypertrophy diagnosed in 100,756 consecutive births. PMID- 1445135 TI - Clitoral hypertrophy and other forms of ambiguous genitalia in the labour ward. PMID- 1445136 TI - Hypothyroidism complicating pregnancy. AB - In this report we describe 26 pregnancies complicated by hypothyroidism cared for over 6.5 years at AIIMS, New Delhi. In 2 women hypothyroidism was diagnosed during pregnancy; others were diagnosed before pregnancy and continued to receive thyroxine replacement therapy throughout pregnancy. The thyroxine treatment needed readjustment in 7 (26.9%) pregnancies to maintain euthyroidism. Maternal complications included anaemia (23.0%), pregnancy induced hypertension (26.9%), postpartum haemorrhage (7.7%), intrauterine growth retardation (15.4%), postdatism (30.8%), and deficient lactation (19.2%). Perinatal mortality was 3.9%. No case of stillbirth occurred probably because of intensive fetal monitoring and timely termination of pregnancies on evidence of intrauterine fetal compromise. One neonatal death occurred due to fetal thyrotoxicosis. In these cases close surveillance during pregnancy is needed to maintain optimum thyroid hormone concentration, and intensive fetal monitoring is required to achieve a good perinatal outcome. PMID- 1445137 TI - Indomethacin for the treatment of polyhydramnios: a case of constriction of the ductus arteriosus. AB - Prenatal administration of indomethacin for the treatment of polyhydramnios at 27 weeks' gestation resulted in the rapid restoration of normal amniotic fluid volume. However, after 16 days therapy, fetal echocardiography revealed constriction of the fetal ductus arteriosus which did not reverse during the 17 days after the therapy was discontinued. The constriction resulted in right heart failure but no long-term effects on the infant after birth. Indomethacin is a powerful treatment for polyhydramnios but its use requires close monitoring of the fetal heart. PMID- 1445138 TI - Campylobacter jejuni in pregnancy. AB - Case notes of pregnancies with proven Campylobacter jejuni infections were collected from 2 Queensland teaching hospitals and reviewed. Of these cases, 2 pregnancies (3 fetuses) resulted in stillbirths, 2 neonates required treatment with antibiotic therapy within 2 days of birth, while the remaining 2 pregnancies were treated at the time of the infection and were not associated with adverse outcome. Maternal Campylobacter infection should be actively sought for in the patient with suspected infectious diarrhoea. PMID- 1445139 TI - Pregnancy following infertility. AB - Pregnancies of 112 patients who had conceived after a history of a minimum of 2 years of infertility were compared to an equal number of matching controls without prior infertility to find out any risk of increased pregnancy complications. These patients were at a significantly higher risk of developing first trimester bleeding, antepartum haemorrhage and intrauterine fetal death. Also there were higher rates of preterm delivery and Caesarean section. The patients in the study group had a significantly higher number of stillborn babies. The incidence of other complications such as ectopic pregnancy, multiple pregnancy, and medical complications was also higher in these patients but the difference was not statistically significant. PMID- 1445140 TI - Diagnostic value of magnetic resonance imaging in gynaecology. AB - In this study 23 patients with various gynaecological pathologies were evaluated. Ultrasonography and magnetic resonance imaging were performed in all cases, but only 14 were evaluated with computed tomography. On the basis of ultrasonography, 4 patients were labelled as having malignant ovarian tumours, however, this diagnosis was confirmed by magnetic resonance imaging in only 1 of the 4. Magnetic resonance imaging also determined the correct diagnosis in a patient with endometrioma whereas computed tomography showed only a simple cyst, and ultrasonography diagnosed a subserous myoma. Tumour was demonstrated by magnetic resonance imaging in 2 patients with cervical carcinoma although computed tomography and ultrasonography had previously shown no tumour mass in these patients. It was concluded that magnetic resonance imaging is much superior to computed tomography and ultrasonography in gynaecological diagnosis. This advantage results from the correct detection of the contents of ovarian cysts, the number and localization of uterine leiomyomas in T2 scans, invasion of uterine malignancies and differential diagnosis of subserous uterine leiomyomas from ovarian tumours. PMID- 1445141 TI - The boldest procedure possible for checking the bleeding--a new look at an old operation, and a series of 13 cases from an Australian hospital. AB - Ligation of the internal iliac (hypogastric) arteries in cases of massive obstetric and gynaecological haemorrhage can be a life-saving operation, but it has never been widely practised in the British gynaecological tradition. There may be historical reasons for this. A series of 13 cases is presented from one Australian hospital over a 5-year period, and a very low rate of Caesarean hysterectomy is demonstrated. A wider knowledge of the technique is recommended. Alternative methods of management, including angiographic embolization and the use of prostaglandins are discussed. PMID- 1445142 TI - Primary adjunctive whole abdominal radiotherapy in epithelial ovarian cancer: results of 10-years' experience. AB - During a 10-year period from January 1, 1979, 59 patients out of a total of 203 undergoing definitive treatment for epithelial ovarian cancer were managed with primary adjuvant whole abdominal radiotherapy after initial cytoreductive surgery. The median survival of this group was 53 months. The serious morbidity rate was approximately 8% with 4 laparotomies for bowel complications and 1 death following radiation related liver failure. This form of adjuvant therapy in appropriately selected patients with minimal residual disease merits further evaluation against other forms of therapy such as systemic or intraperitoneal chemotherapy. PMID- 1445143 TI - Urethral instability. AB - Urethral instability is still evolving as a clinical entity. Using pressure variation of 15 cm water or more at the point of maximum urethral pressure (MUP), urethral pressure profilometry on patients referred for urodynamic assessment for lower urinary tract symptoms revealed urethral instability in 6.4% of 608 patients. The close association between urethral and detrusor instability was noted. Urethral instability appears to be a cause of frequency and urgency of micturition, and its presence increase the risk of urinary incontinence. PMID- 1445144 TI - Eisenmenger syndrome in pregnancy. PMID- 1445145 TI - Thrombotic thrombocytopenic purpura in pregnancy. PMID- 1445146 TI - Transabdominal ultrasound assessment of cervical dilatation in preterm labour. PMID- 1445148 TI - Endometrial ablation under local analgesia. PMID- 1445147 TI - Uterine rupture after induction of labour for intrauterine death using the prostaglandin E2 analogue sulprostone. PMID- 1445149 TI - Haematometra--a complication of endometrial ablation. PMID- 1445150 TI - Balance and gait analysis after 30 days -6 degrees bed rest: influence of lower body negative-pressure sessions. AB - Five volunteers took part in -6 degrees head-down bed-rest experiments for 30 d. In the first experiment, three subjects underwent several sessions of lower-body negative-pressure (LBNP) per day, with two others serving as controls. In the second, the LBNP group of the first experiment became the control and vice versa. Two experimental protocols analyzed the bed-rest-induced modifications of balance and gait and the efficiency of LBNP in counteracting these modifications. A kymographic method allowed the measurement of walking parameters. Anteroposterior and lateral sways were successively studied with both a force platform (static condition) and a rocking platform (dynamic condition). The tests were performed 2 d before the bed-rest period, and over the 1st, 3rd and 4th days of the recovery period. When the subjects were controls, bed rest decreased step length, walking velocity, and balance stability. LBNP completely counteracted the bed-rest induced modifications of gait and static balance and of dynamic balance for the lateral sway. As LBNP was ineffective in counteracting the modifications of the anteroposterior sway, dynamic balance deficiency was independent of the beneficial effect of LBNP on the decreased orthostatic tolerance induced by -6 degrees head-down bed rest. The results indicate that head-down bed rest, like spaceflight, induces certain sensorimotor changes involved in the decrease of gait and balance performance. PMID- 1445151 TI - Hyperbaric oxygen treatment for carbon monoxide poisoning in pregnancy: a case report. AB - Carbon monoxide (CO) poisoning is one of the most common forms of poisoning in the United States. When CO poisoning occurs in the pregnant patient, it is extremely toxic to the mother and fetus in terms of central nervous system disorders and delayed central nervous system sequelae. Controversy exists in treating the pregnant patient with hyperbaric oxygen (HBO) because of the unknown effects of high partial pressures of oxygen on the fetus. HBO therapy is beneficial in CO poisoning because of its effect of first increasing oxygen concentration and causing a shift in the oxygen dissociation curve from the left to the right. Second, by causing a diminished CO interaction with cytochrome oxidase, HBO allows mitochondria to use oxygen more effectively. Third, HBO may reduce lipid peroxidation which may be responsible for neurological deterioration and delayed central nervous system sequelae. Fourth, decreased CO influence through HBO may reduce changes in the myocardium as a result of CO poisoning, if cardiovascular disease is already present. A case study of successful HBO therapy used during pregnancy is presented and effects of CO on the fetus are discussed. PMID- 1445152 TI - Psychiatric diagnoses aboard an aircraft carrier. AB - A descriptive study was conducted for 150 consecutive patients with a psychiatric diagnosis evaluated over 11 months by the medical staff onboard an aircraft carrier. Patients with sole diagnosis of alcohol abuse or dependence were excluded. Axis II diagnoses, or personality disorders, were more common (N = 120) than Axis I diagnoses (N = 46). The most common Axis I diagnoses were adjustment disorder and major depression. Axis II diagnoses were significantly more likely (OR = 7.33, 95% CI 4.45-12.16, p = 0.000) in sailors less than 23 years of age compared to ship's population. Suicide behavior was demonstrated in 68% (102/150) of the patient population. This study emphasized the requirement for extensive psychiatric training for the clinical aerospace medicine specialists providing operational support to aircraft carrier crews. PMID- 1445153 TI - Radiated electric field measurements in U.S. Army helicopters. AB - Aircraft systems and medical devices generate electromagnetic fields. Electromagnetic interference (EMI) can cause faulty operation of aircraft systems or medical devices and endanger patients or aircraft crewmembers. A ground and inflight study was conducted to describe the electromagnetic fields in typical operations. Broadband isotropic field sensors measured electric fields from 5 kHz to 3 MHz, 3 to 500 MHz, and 0.5 MHz to 6 GHz. Fields were measured at 0.5 m space intervals in JOH-58A, JUH-1H, and JUH-60A helicopters with systems off, operating RPM, 5-ft hover, 50-ft hover, and cruise. Electric fields in the environment were homogeneous and less than 0.1 V/m. Fields in the helicopters increased during ascent, but remained less than 2 V/m except during radio transmissions. EMI effect of the Physio Control Lifepack 8 was demonstrated during FM radio transmission. The results are useful in evaluating electromagnetic emissions and predicting operations that may result in an inflight malfunction of a medical device or aircraft system. PMID- 1445154 TI - Potential hazards of high anti-Gz suit protection. AB - Although balanced positive pressure breathing increases protection by G suits and reduces fatigue during sustained high Gz exposures, it does not prevent dependent pulmonary right-to-left shunts (arterial hypoxemia) and potentially dangerous distention of nondependent alveoli. An incident of acute incapacitating mediastinal emphysema in a healthy young man during a sustained exposure to 5.5 Gx documents this possibility. This, plus neurogenic bradycardia during sustained high Gz exposures without pressure breathing, suggests that testing of full counterpressure to neck level suits at sustained > 9 Gz exposures may be hazardous. Fully instrumented studies of animal surrogates with comparable thoracic dimensions are indicated. PMID- 1445155 TI - Say no to drugs of abuse. PMID- 1445156 TI - Anniversary congratulations. PMID- 1445157 TI - Pilot performance with blood alcohol concentrations below 0.04%. AB - The effects of a low (less than 0.04%) BAC on pilot performance were investigated in a series of four experiments in which pilots flew a light aircraft simulator under alcohol and placebo conditions. The mean BACs of subjects when starting and finishing the test sessions were 0.037% and 0.028%, respectively. Two of the experiments involved demanding flight tasks under instrument meteorological conditions: complicated departure, holding, and approach procedures in one case; and VOR-use intersection problems in the other. The other two experiments involved ILS approaches under turbulence, cross wind, and simulated wind shear conditions that imposed heavy control-task loads on the pilots. Significant alcohol effects were found, but only under the heaviest workload conditions. During posttest interviews 75% of the pilots reported physical and/or mental effects due to alcohol. PMID- 1445158 TI - Success rate analysis of Navy SERGRAD flight training. AB - SERGRADS are selectively retained graduates of Naval Flight Training who become flight instructors during their first tour as Naval Aviators. A perception exists that SERGRADS have more difficulties than newly designated pilots during subsequent training in the Fleet Replacement Squadrons (FRS). A preliminary inquiry at the F/A-18 FRS revealed that former SERGRADS appear to experience a higher rate of failure on their initial carrier qualification attempt during FRS training. This study examined the SERGRAD experience and compared their performance to trainees from other sources. Although significant differences were found between groups for Fleet Replacement Squadron flight grades and Training Command composite grades, no significant differences were found between the groups for Training Command carrier qualification grades or Fleet Replacement Squadron carrier qualification. Thus, the data do not support the hypothesis that SERGRADS have more problems or are poorer aviators than F/A-18 students from other sources. PMID- 1445159 TI - Time to detection of circulating microbubbles as a risk factor for symptoms of altitude decompression sickness. AB - This study investigated the association between time at onset of circulating microbubbles (CMB) and symptoms of altitude decompression sickness (DCS), using Cox proportional hazard regression models. The study population consisted of 125 individuals who participated in direct ascent, simulated extravehicular activities profiles. Using individual CMB status as a time-dependent variable, we found that the hazard for symptoms increased significantly (at the end of 180 min at altitude) in the presence of CMB (Hazard Ratio = 29.59; 95% confidence interval [95% CI] = 7.66-114.27), compared to no CMB. Further examination was conducted on the subgroup of individuals who developed microbubbles during the test (n = 49), by using Cox regression. Individuals with late onset of CMB (> 60 min at altitude) showed a significantly reduced risk of symptoms (hazard ratio = 0.92; 95% CI = 0.89-0.95), compared to those with early onset (< or = 60 min), while controlling for other risk factors. We conclude that time to detection of circulating microbubbles is an independent determinant of symptoms of DCS. PMID- 1445160 TI - Failure of the straight-line DCS boundary when extrapolated to the hypobaric realm. AB - The lowest pressure (P2) to which a diver can ascend without developing decompression sickness (DCS) after becoming equilibrated at some higher pressure (P1) is described by a straight line with a negative y-intercept. We tested whether extrapolation of such a line also predicts safe decompression to altitude. We substituted tissue nitrogen pressure (P1N2) calculated for a compartment with a 360-min half-time for P1 values; this allows data from hypobaric exposures to be plotted on a P2 vs. P1N2 graph, even if the subject breathes oxygen before ascent. In literature sources, we found 40 reports of human exposures in hypobaric chambers that fell in the region of a P2 vs. P1N2 plot where the extrapolation from hyperbaric data predicted that the decompression should be free of DCS. Of 4,576 exposures, 785 persons suffered decompression sickness (17%), indicating that extrapolation of the diver line to altitude is not valid. Over the pressure range spanned by human hypobaric exposures and hyperbaric air exposures, the best separation between no DCS and DCS on a P2 vs. P1N2 plot seems to be a curve which approximates a straight line in the hyperbaric region but bends toward the origin in the hypobaric region. PMID- 1445161 TI - Electromyographic activity while performing the anti-G straining maneuver during high sustained acceleration. AB - The purpose of this study was to measure the muscle activity during performance of the anti-G straining maneuver (AGSM) at high sustained acceleration stress (+Gz = head-to-foot inertial loading). Ten males were exposed on three separation occasions to a rapid onset rate of 6 + Gz. Subjects wore standard United States Air Force (USAF) anti-G trousers and performed the AGSM until perceived fatigue or until achieving light loss criteria. During each exposure, surface electromyography (EMG) was recorded from the erector spinae, external oblique, bicep femoris, vastus lateralis, and lateral gastrocnemius muscles. The normalized root-mean squares (RMS) and mean power frequency (MPF) for each muscle were calculated and tested for significant differences with an analysis of variance (ANOVA) procedure. The results of this study showed that mean amplitude decreased during the AGSM (35.40%) while MPF showed no significant change. The EMG amplitude of lower extremity muscles decreased (61.45%) while the amplitude of trunk muscles decreased slightly (3.45%). These results indicate that during the performance of the AGSM, motor unit recruitment in lower extremity muscles decrease without evidence of fatigue. PMID- 1445162 TI - The effects of hypoxia on auditory reaction time and P300 latency. AB - A predominant feature of hypoxia is that it slows information processing. Evidence is accumulating that early visual mechanisms are an important locus of this slowing. Audition is believed to be insensitive to hypoxia, implying relatively less slowing with auditory stimuli. Subjects breathed air or a low oxygen mixture (65% arterial oxyhemoglobin saturation) while RT (reaction time) and the EEG were collected to oddball binaural tone pips at 500 Hz, 1000 Hz, and 4000 Hz. Hypoxia slowed RT and the event-related brain potential P300 in a correlated manner and by an identical amount that was generally independent of frequency. On the assumption that P300 indexes the time to evaluate a stimulus and RT indexes this time plus the time to select and execute a response, stimulus evaluation is implicated as a major locus of slowing in this experiment. The amount of slowing was comparable to that found previously with RT and P300 to visual stimuli. It may be that audition is more sensitive to hypoxia than is currently believed, at least where the speed of processing is concerned. PMID- 1445163 TI - Seasonal effects on human physiological adaptation factors, thermotolerance and plasma fibronectin. AB - Plasma fibronectin (PF) influences shock survival and basal levels increase with active conditioning that improves human physiological adaptation factors (PAF) and thermotolerance (TT). To evaluate further PF's relationship with PAF and TT, the effects of passive conditioning with seasonal change (spring vs. summer) in New England on PAF, TT, basal PF level and PF level during hot-humid exercise (HHE; bicycling; 40 +/- 4% VO2max; 35 degrees C; 70% rh; 45 min) were examined in male subjects (28.2 +/- 1.6 years; N = 7; values are means +/- SE). The spring and summer studies were separated by 2 months. In addition, 2 months prior to the spring study, a winter basal PF pre-screening was conducted. Winter (287 +/- 36 micrograms/ml), spring (272 +/- 21 micrograms/ml), and summer (278 +/- 19 micrograms/ml) basal PF levels were similar. The PF response during HHE was unremarkable with seasonal change. PAF were improved, since blood volume (6266 +/ 276 vs. 5895 +/- 251 ml), plasma volume (3896 +/- 198 vs. 3601 +/- 165 ml) and HHE sweat rate (18.7 +/- 5.5 vs. 12.9 +/- 6.4 ml/min) were elevated (p < 0.05) in the summer compared to the spring. However, this was not accompanied by improved TT, since spring and summer rectal temperatures during HHE were similar, while summer heart rate was elevated (p < 0.05) compared to the spring. In contrast to active conditioning, passively-induced improvements in PAF were not associated with elevations in TT or PF level. Unlike PAF, PF elevations might only occur when the conditioning resulted in increased TT, which suggests a potential for PF as a TT marker. PMID- 1445164 TI - Accuracy of aimed arm movements in changed gravity. AB - We studied the accuracy of aimed arm movements in normal gravity, and during the hypergravity (hyper-G) and microgravity (micro-G) episodes of KC-135 parabolic flights. Subjects pointed at mirror-viewed targets without sight of their arm, and final pointing position was measured by a digitizing pad. Compared with the normal gravity (normal-G) baseline, subjects pointed consistently higher in hyper G, and still higher in micro-G. Results were not different if subjects viewed targets only during normal-G and pointed at their memorized position under changed gravity (changed-G); this suggests that the "elevator illusion" played a minor role in our study. The observed impairments were attributed to degraded proprioceptive feedback and/or inappropriate motor programs in changed-G. Pointing accuracy improved movement-to-movement but not parabola-to-parabola, indicating that prolonged exposure is needed for sustained adaptation. PMID- 1445165 TI - Effects of acute exercise on attenuated vagal baroreflex function during bed rest. AB - We measured carotid baroreceptor-cardiac reflex responses in six healthy men, 24 h before and 24 h after a bout of leg exercise during 6 degrees head-down bed rest to determine if depressed vagal baroreflex function associated with exposure to microgravity environments could be reversed by a single exposure to acute intense exercise. Baroreflex responses were measured before bed rest and on day 7 of bed rest. An exercise bout consisting of dynamic and isometric actions of the quadriceps at graded speeds and resistances was performed on day 8 of bed rest and measurements of baroreflex response were repeated 24 h later. Vagally mediated cardiac responses were provoked with ramped neck pressure-suction sequences comprising pressure elevations to +40 mm Hg, followed by serial, R-wave triggered 15 mm Hg reductions, to -65 mm Hg. Baroreceptor stimulus-cardiac response relationships were derived by plotting each R-R interval as a function of systolic pressure less the neck chamber pressure applied during the interval. Compared with pre-bed rest baseline measurements, 7 d of bed rest decreased the gain (maximum slope) of the baroreflex stimulus-response relationship by 16.8 +/- 3.4% (p < 0.05). On day 9 of bed rest, 24 h after exercise, the maximum slope of the baroreflex stimulus-response relationship was increased (p < 0.05) by 10.7 +/ 3.7% above pre-bed rest levels and 34.3 +/- 7.9% above bed rest day 7. Our data verify that vagally-mediated baroreflex function is depressed by exposure to simulated microgravity and demonstrate that this effect can be acutely reversed by exposure to a single bout of intense exercise. PMID- 1445166 TI - Liver disease, carbohydrate metabolism and diabetes. PMID- 1445167 TI - Chronic pancreatitis and diabetes. AB - Chronic pancreatitis is defined by a persistent destruction of the pancreatic parenchyma replaced by fibrosis. The lesions generally start in the exocrine gland, islets being attacked later in the fibrosis. The two most frequent forms are: 1. Chronic calcifying pancreatitis which is a pancreatic lithiasis responsible for more than 95% of chronic pancreatitis. In its most frequent form, calculi are built up of more than 98% calcium salts together with fibres of a degraded residue of lithostathine, a secretory protein. This disease is related (i) in most countries to alcohol, protein, fat and tobacco and (ii) in certain tropical countries to malnutrition (low-fat, low-protein diet) for some generations. A causative role for cassava and kwashiorkor is improbable. The mechanism of calcium precipitation is partly explained by the calcium-saturation of pancreatic juice and the decreased biosynthesis of lithostathine S, the secretory protein preventing crystallization. As a rule, diabetes (and steatorrhoea) appear after a clinical evolution characterized by recurrent attacks of upper abdominal pain, generally lasting some days with transiently increased concentrations of pancreatic enzymes in serum. When diabetes appears, pain frequently disappears. Complications are mostly observed in the first 10 years of clinical evolution. 2. Obstructive pancreatitis is due to an obstacle (tumours, scars) in the pancreatic duct. It is rarely a cause of diabetes. Diabetes due to chronic pancreatitis is characterized by the low incidence of ketosis and the high incidence of insulin-induced hypoglycaemia. Patients are generally thin. Serum insulin levels, either basal or stimulated, are decreased. Glucagon is less affected. Angiopathies and retinopathies are less frequent than in non-insulin-dependent diabetes. Neural complications are fairly frequent. The diagnosis is generally easy because diabetes appears at a late stage of the disease. The treatment generally requires insulin. PMID- 1445168 TI - Diabetes secondary to tropical calcific pancreatitis. PMID- 1445169 TI - Diabetes mellitus and cystic fibrosis. AB - There is a high prevalence of diabetes mellitus in patients with CF and this is likely to increase in the future as more patients are surviving into adult life. In view of this all CF clinics should routinely screen for diabetes mellitus. The prevalence of diabetes mellitus in adult CF patients is higher than in children, and the onset is commonly insidious. The diabetes seen in CF is not classical Type 1 diabetes or Type 2 diabetes and could more helpfully be called cystic fibrosis-related diabetes (CFRD). Treatment is by oral hypoglycaemic agents or insulin. It is not appropriate to control patients by diet alone. Dietary advice to CF diabetic patients is not the same as that given to non-CF diabetic patients. Microvascular complications have now been reported and careful monitoring of all CF patients with diabetes should be undertaken. PMID- 1445170 TI - Haemochromatosis and diabetes. PMID- 1445171 TI - Growth hormone disorders and secondary diabetes. PMID- 1445172 TI - Diabetes and adrenal disease. AB - Disorders of the adrenal cortex and medulla can result in glucose intolerance or overt diabetes mellitus. Cushing's syndrome, characterized by excessive secretion of glucocorticoids, impairs glucose tolerance primarily by causing insulin resistance at the post-receptor level. On the other hand, phaeochromocytoma and hyperaldosteronism, via the respective actions of catecholamines and hypokalaemia on the pancreatic beta-cell, impair glucose tolerance primarily by inhibiting insulin release. The glucose intolerance associated with these adrenal disorders is usually only mild to moderate in severity. Marked hyperglycaemia, glycosuria, and polyuria are uncommon and ketosis is rare. Moreover, the late complications of diabetes mellitus are distinctly uncommon in patients with these disorders, and the prognosis for morbidity and death is usually that of the underlying disease and not that of diabetes mellitus. The impaired glucose tolerance induced by all three of these adrenal disorders usually returns to normal once the underlying aetiology has been cured. These factors must guide the clinician in treatment of these secondary forms of diabetes, and suggest that tight (near normal) blood glucose control may not be an appropriate goal in patients with these disorders. The relationship between adrenal androgens and glucose tolerance is more uncertain. Several studies in humans have demonstrated an acute decline in serum concentrations of the adrenal steroids DHEA and DHEA-sulfate in response to experimentally-induced hyperinsulinaemia, but the regulatory role of insulin on adrenal androgen metabolism in normal physiology or disease remains speculative. In several animal models DHEA appears to exert potent anti-obesity and anti-diabetogenic actions, but such effects have yet to be demonstrated in humans. Human studies of DHEA are limited, and more research needs to be conducted to determine whether the observations made in animal models will prove applicable to man. PMID- 1445173 TI - Drug-induced diabetes. AB - The only drugs which commonly cause diabetes during therapeutic use are the anti hypertensive vasodilator diazoxide, and corticosteroids in high doses such as those used to palliate intracranial tumours. Thiazide diuretics have in the past been used in higher doses than necessary to treat hypertension, and the lower doses now used probably carry only a slight risk of inducing diabetes. The risk from beta-blockers is also quite small, but there is some evidence that thiazides combined with beta-blockers may be more likely to cause diabetes than either drug alone. The combination is probably best avoided in patients with a family history of non-insulin-dependent diabetes. The effect of the low-oestrogen combined oral contraceptive pill seems to be slight, and it presents a risk only to women who have had gestational diabetes. Bodybuilders who take enormous doses of anabolic androgens can develop impaired glucose tolerance. Several drugs, including theophylline, aspirin, isoniazid and nalidixic acid can cause transient hyperglycaemia in overdosage, but only streptozotocin, alloxan and the rodenticide Vacor are likely to cause permanent diabetes. PMID- 1445174 TI - Diabetes secondary to genetic disorders. AB - Diabetes may be associated with many genetic disorders. The scientific importance of these often rare disorders resides in the insight they may provide into the possible mechanisms of common diabetes. The type of diabetes varies in these syndromes. Non-insulin-dependent diabetes (NIDDM), clinically similar to common NIDDM, may be found in some syndromes (e.g. Werner's syndrome). In others there may be considerable insulin resistance, such as that present in ataxia telangiectasia. Extreme insulin resistance due to abnormal insulin receptor function is found in the Mendenhall syndrome. The mechanism of diabetes is more obscure in acute intermittent porphyria (AIP), although haem deficiency affecting the cytochrome chain raises interesting possibilities. In glycogen storage disease type I, the diabetes is associated with insulinopenia, following an earlier period in the disease when hypoglycaemia is the rule. IDDM, clinically similar to the common form, is present in the autoimmune polyglandular syndromes. Although a change in the lean:fat ratio is common in many neuromuscular disorders, mechanisms other than insulin resistance would seem to operate. The increased incidence of diabetes in heterozygotes for some of these genetic disorders raises the possibility that many common diabetics are, in fact, heterozygotes for some other disorder. The increased frequency of diabetes in Klinefelter's syndrome, Turner's syndrome and possibly Down's syndrome leads to the hypothesis that non-disjunction may, in some way be associated with the predisposition to diabetes. In several syndromes there is an increased incidence of diabetes in otherwise unaffected relatives of individuals with these syndromes. It is impossible to assess what proportion of common NIDDM or IDDM is made up of heterozygotes for these genetic syndromes. PMID- 1445175 TI - APUDomas and diabetes mellitus. PMID- 1445176 TI - Incidence of trypanosomes and productivity of settled Fulani cattle in Anambra State, southern Nigeria. AB - In the tropical rain forest zone of Southern Nigeria Fulani zebus were investigated for the incidence of trypanosomes. The animals had been settled in this area for at least 3 years. Although cattle in the southern part of the country exhibited a significantly higher incidence of trypanosomes than cattle in the northern parts they are more robust and healthier and showed a higher reproductive performance than cattle in Northern Nigeria. Thus the tse-tse fly attacks are no hindrance to cattle production in Southern Nigeria, Anambra State. PMID- 1445177 TI - Some physiological aspects of repeat breeding in Holstein Friesians and its improvement under Egyptian environment. AB - The serum albumin concentration and the albumin-globulin ratio had a significant effect on the rate of repeat breeding. In repeat breeders, low concentrations were found of albumin, progesterone, phosphorus, zinc, and glucose. The glycogen content of the cervical mucus was significantly lower in the repeat breeders. Treating repeat breeders with prostaglandin F2 alpha had positive effects on the parameter values. PMID- 1445178 TI - Adenine phosphoribosyl transferase polymorphism in baboons. AB - Two allelic isozymes of adenine phosphoribosyl transferase (APRT) were detected by starch gel electrophoresis of baboon hemolysates. Extensive family data verified autosomal codominant inheritance. The gene frequencies of five subspecies of baboons differed significantly. The activity of erythrocyte APRT is sufficiently high to enable the use of this enzyme as a sensitive marker for assessing chimerism in research involving bone marrow transplantation. PMID- 1445180 TI - The relationship between homozygosity level and animal physiology: iron content of plasma and whole blood as well as total iron binding capacity by transferrin (TIBC) in rats of various inbreeding coefficient. AB - Male and female wild Norway rats (Rattus norvegicus Erxleben) and male and female albino outbred rats (Ipf:RIZ) were crossbred. These animals were the control, noninbred group (0% inbred). By systematic full-sib mating, two experimental groups (50 and 91% of inbred) were raised. Half of each group (both males and females) was exposed to physical stress (3 days of starvation and 3 hr of swimming). The other half of each group was ether anesthetized to collect blood. The iron content of plasma and whole blood, as well as the total iron binding capacity, was determined by the Atom-Spec method. A significant decrease in the iron content of plasma and whole blood as well as the TIBC was observed by an increase in the inbreeding coefficient. Stress significantly influenced the iron content of plasma and whole blood as well as the TIBC, whereas the sex of the rats affected the whole-blood iron concentration and TIBC. Moreover, some double interactions had an impact on the iron content and TIBC. The interactions were as follows: plasma--inbreeding level and stress; whole blood--sex and stress; and TIBC--inbreeding level and sex. PMID- 1445179 TI - A polymorphism detected in a variable number of tandem repeats (VNTR) of the seminal vesicle secretion (SVS) IV gene in inbred rats. AB - The second intron of the rat SVS IV gene contains a tandem repeat region of 20-bp sequences. This region was amplified using the polymerase chain reaction to detect variations. Three alleles, characterized by amplified fragments of 750, 490, and 390 bp, respectively, were found in 24 strains examined. This variation segregated in F1 and backcross progeny in an autosomal codominant manner. We tentatively designated this locus Svs-4. Analysis of linkages between the Svs-4 locus and other loci revealed that it was closely linked to the Svp-1 (less than 2.9%) and the a (10.0 +/- 6.7%) loci, which belong to rat linkage group IV. The Svp-1 and Svs-4 loci, however, were differently distributed among the inbred rat strains. PMID- 1445181 TI - Analysis of L-alanine:2-oxoglutarate aminotransferase isozymes in maize. AB - Isozyme analysis of L-alanine:2-oxoglutarate aminotransferase (ALT) in maize indicates that there are three genes encoding this enzyme activity. Two of the gene products interact with each other to form heterodimers, while the third gene product does not interact with the other two. Another isozyme that appears after gel electrophoresis and ALT staining is shown to be glutamate dehydrogenase-1. Anaerobic treatment does not result in increased ALT levels, indicating that the previously reported increase in alanine levels caused by this treatment may be due to increases in the level of pyruvate, a substrate of ALT. PMID- 1445182 TI - Heterogeneity of the hemoglobin of the Ohrid trout (Salmo L. typicus). AB - We have analyzed the hemoglobins of five individual trout from the Ohrid Lake (Salmo L. typicus) by electrophoretic methods, by reversed-phase high-performance liquid chromatography, and by limited structural analyses. The two major classes of hemoglobin are type I (35% of total) and type IV (65%). Type IV is the major oxygen-transporting hemoglobin; it consists of three types of beta chain (in about equal quantities) and three types of alpha chain (one major and two minor types). Several structural differences have been observed between these three beta (IV) chains and between the three alpha (IV) chains, suggesting a complex genetic system governing the synthesis of these proteins. Moreover, a few amino acid substitutions occur at positions involved in contacts between chains, which suggests that differences in oxygen affinity may exist between these various type IV hemoglobins. Type I hemoglobin is less complex because it contains one type of beta chain and two alpha chains; the latter two differ in numerous positions, suggesting duplications of the alpha (I)-globin gene. The alpha and beta chains of type I hemoglobin differ considerably from the alpha and beta chains of type IV hemoglobin, indicating the existence of alpha (I)- and beta (I)-globin genes separate from the alpha (IV)- and beta (IV)-globin genes. PMID- 1445183 TI - Epidermolysis bullosa simplex: expression of gelatinase activity in cultured human skin fibroblasts. AB - We have measured the baseline level of gelatinase in fibroblast-conditioned medium from 41 Scandinavian individuals. They comprised 12 healthy persons, 11 individuals with the skin disorder dominant epidermolysis bullosa simplex (DEBS), 16 patients with other types of epidermolysis bullosa (EB) and 2 siblings with prolidase deficiency. These results divide the cell strains into those with low and those with high activity levels. Although this dual biochemical trait occurred in all the groups of individuals, the high-activity trait was more frequent among the DEBS patients. The localized DEBS forms showed an elevated activity level, in contrast to the previously reported generalized DEBS Kobner forms. Although a high level was found in some individuals with other EB forms, the high incidence in four families with localized DEBS Weber-Cockayne (eight of eight) and a single family with generalized DEBS--mottled pigmentation (two of two) may result from a close linkage between an EB gene and a gene responsible for the biochemical trait. In addition, in the single complete family tested, the level of gelatinase activity in cultured fibroblasts seemed to be regulated by codominant alleles or genes. A raised baseline level of gelatinase activity in cultured skin fibroblasts may be the result of either an altered expression of gelatinase or an allelic variant of this enzyme with increased specific activity. Further studies of gelatinase in cultured fibroblasts may provide insight into the regulatory mechanism and genetics behind this activity and allow formal linkage studies versus DEBS. PMID- 1445184 TI - Esterase-29 (ES-29): biochemical characterization and control by two independent gene loci of a testosterone-dependent mouse serum esterase. AB - Biochemistry and genetics of a testosterone-dependent murine serum esterase designated esterase-29 (ES-29) are described. The enzyme was identified after disc electrophoresis and subsequent staining for esterase using alpha-naphthyl acetate as the substrate. It was inhibited by bis-p-nitrophenyl phosphate and was resistant to p-chlorophenylsulphonate and hence was classified as carboxylesterase EC3.1.1.1. The molecular mass was estimated to be about 130 kDa. It was shown that ES-29 is under the control of two independent genes. The first, termed Es-29, is suggested to be a structural locus, linked to the cluster-2 esterase loci on chromosome 8. Three alleles at Es-29, Es-29a, Es-29b, and Es-29c are distinguished, which determine absence (SEG/1), strong activity (BALB/cJ), and low activity (MOLH/Fre), respectively. The second locus, termed Mse-1 (serum esterase modifying factor), was found to be closely linked to Pre-2 on chromosome 12 and is suggested to be a modifying or regulatory gene. Two alleles were distinguished, Mse-1a (BALB/cJ) and Mse-1m (MOL3/JA, Cas-Bgr), which determine whether ES-29 appears as a single band or a double band, respectively. Mse-1m is dominant to Mse-1a. PMID- 1445185 TI - Both chloroplast and mitochondrial NADH dehydrogenase subunit 5 genes are transcribed in pea. PMID- 1445186 TI - Allozyme variation in bumble bees (Hymenoptera: Apidae). AB - Allozyme variation at an average of 37.3 loci was assessed in queens of 16 Bombus and 2 Psithyrus bumble bee species from North America. The mean expected heterozygosity (H) for the Bombus species was 0.008 +/- 0.006 (95% confidence limits) and that for the Psithyrus was 0.007 +/- 0.007. These levels are significantly lower than found in other Hymenoptera but are comparable to those found in previous studies of bumble bees based on far fewer loci. Neutral mutation and random genetic drift can account for the observed variation, but this implies a very small effective population size for species of bumble bees. PMID- 1445188 TI - Inheritance of malate dehydrogenase nulls in soybean. AB - Three chlorophyll-deficient mutants (CD-1, CD-2, and CD-3), derived from the progeny of independent germinal revertants from the w4-mutable soybean line [Glycine max (L.) Merrill], were characterized genetically. Electrophoretic analyses indicated that these lines lacked two of three mitochondrial malate dehydrogenase isozymes (MDH-). The absence of two MDH bands was conditioned by a recessive allele at a locus designated Mdh1. All three CDs were allelic to each other and to T253, a Harosoy isoline y20-k2 MDH- from the Genetic Type Collection. The MDH- phenotype and the yellow-green plant phenotype were each inherited as single recessive alleles. No recombination between the two traits was found in nine F2 populations from crosses of the CDs by wild-type soybean lines. Complete linkage of the Mdh1 and y20 loci suggested that the mutations in the chlorophyll-deficient lines were deletions. Phenotypic differences among the CDs suggested that the deletions may have different endpoints. The chromosomal aberrations were not large enough to affect transmission of y20 and Mdh1 mutant alleles through the pollen or ovule. CD-1, CD-2, and CD-3 were added to the Soybean Genetic Type Collection as T323, T324, and T325, respectively. PMID- 1445187 TI - Chinook salmon NADP(+)-dependent cytosolic isocitrate dehydrogenase: electrophoretic and genetic dissection of a complex isozyme system and geographic patterns of variation. AB - Species in the genus Oncorhynchus express complicated isocitrate dehydrogenase (IDHP) isozyme patterns in many tissues. Subcellular localization experiments show that the electrophoretically distinct isozymes of low anodal mobility expressed predominantly in skeletal and heart muscle are mitochondrial forms (mIDHP), while the more anodal, complex isolocus isozyme system predominant in liver and eye is cytosolic (sIDHP). The two loci encoding sIDHP isozymes are considered isoloci because the most common allele at one of these loci cannot be separated electrophoretically from the most common allele of the other. Over 12 electrophoretically detectable alleles are segregating at the two sIDHP* loci in chinook salmon. Careful electrophoretic comparisons of the sIDHP isozyme patterns of muscle, eye, and liver extracts of heterozygotes reveal marked differences between the tissues with regard to both relative isozyme staining and the expression of several common alleles. Presumed single-dose heterozygotes at the sIDHP isolocus isozyme system exhibit approximate 9:6:1 ratios of staining intensity in liver and eye, while they exhibit approximate 1:2:1 ratios in skeletal muscle. The former proportions are consistent with the equal expression of two loci (isolocus expression), while the latter are consistent with the expression of a single locus. Screening of over 10,000 fish from spawning populations and mixed-stock fishery samples revealed that certain variant alleles (*127, *50) are detectable only in liver and eye, while other alleles (*129, *94, and *74) are strongly expressed in muscle, eye, and liver. The simplest explanation for these observations is that the "isolocus" sIDHP system of chinook salmon (and that of steelhead and rainbow trout) results from the expression of two distinct loci (sIDHP-1* and sIDHP-2*) that have the same common allele (as defined by electrophoretic mobility). IDHP expression in skeletal muscle is due to the nearly exclusive expression of the sIDHP-1* locus, while IDHP expression in eye and liver tissues is due to high levels of expression of both sIDHP-1* and sIDHP-2*--giving rise to the isolocus situation in these latter tissues. Direct inheritance studies confirm this model of two genetically independent (disomic) loci encoding sIDHP in chinook salmon. Extensive geographic surveys of chinook salmon populations from California to British Columbia reveal marked differences in allele frequencies at both sIDHP-1* and sIDHP-2* and considerably more interpopulation differentiation than was recognized previously when sIDHP was treated as an isolocus system with only five recognized alleles.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1445189 TI - Comparison of the rates of muscle protein metabolism between the domestic and the wild coturnix quail. PMID- 1445190 TI - Assignment of 6-phosphogluconate dehydrogenase and malate dehydrogenase to chromosome 3 of Anopheles stephensi. AB - Genetics and linkage analysis of 6-phosphogluconate dehydrogenase (6-PGD) and malate dehydrogenase (MDH) have been investigated in Anopheles stephensi. Both these markers were found to be autosomal and linked and have been assigned to linkage group III. Two mutant markers, Black larva (Bl) and golden-yellow larva (gy), were used to establish the map distances, and the current sequence of loci on chromosome 3 is as follows: Bl (3.75)-gy (14.53)-Mdh-2 (49.83)-6-pgd. PMID- 1445191 TI - Isolation of a Drosophila gene encoding glutathione S-transferase. AB - We have isolated a Drosophila gene, DmGST-2, that encodes glutathione S transferase, a homo- or heterodimeric enzyme thought to be involved in detoxification of xenobiotics, including known carcinogens. The encoded protein has a primary sequence that is more similar to mammalian placental and nematode GSTs than that of a previously described Drosophila GST gene, herein referred to as DmGST-1. We provide a physical map of the gene and show that it specifies at least two mRNAs, measuring 1.9 and 1.6 kb, which differ only in the lengths of their 3' untranslated regions. Both of the mRNAs are present during all developmental stages. In situ hybridization of the DmGST-2 gene to larval polytene chromosomes places it within the 53F subdivision of chromosome 2, and Southern blotting to chromosomal DNA indicates that the gene has no close relatives within the Drosophila genome. Our results make possible molecular genetic approaches for further elaborating the function of glutathione S transferases in insect development and physiology, in the metabolism of plant toxins, and in conferring insecticide resistance. PMID- 1445193 TI - A positive regulator of the ribosomal protein gene, beta factor, belongs to the ETS oncoprotein family. AB - The beta factor, which interacts with the rpL32 promoter, binds to the sequence 5'-GAGCCGGAAGTG and trans-activates this gene. Comparison of the DNA sequences bound by the beta factor with those bound by other known DNA-binding proteins revealed that the ETS proteins interact with similar DNA sequences. Consequently we have examined the relationship of the beta factor to the several ETS proteins so far reported. Antibody and oligonucleotide competition experiments, performed by using electrophoretic shift analysis, revealed that the beta factor contains ETS epitopes and that it is immunologically related to both of the GA-binding proteins (GABPs), implying that the beta factor may consist of two separate protein subunits. PMID- 1445194 TI - Purification and characterization of a carboxylesterase involved in insecticide resistance from the mosquito Culex quinquefasciatus. AB - A carboxylesterase (EC 3.1.1.1) involved in organophosphate insecticide resistance has been purified and characterized from the mosquito Culex quinquefasciatus. The monomeric enzyme has M(r) of 67,000 and a pI of 5.2. It hydrolysed medium-chain-length mono- and di-acylglycerols in addition to xenobiotic esters. Kinetic constants determined for four insecticides, temephos, chlorpyrifos, fenitrothion and propoxur indicate the rates of acylation and the affinities of binding of the insecticides to this carboxylesterase are important. This supports the major role of the A2 carboxylesterase is the sequestration of the insecticide with a minor role in the slow turnover of the insecticide. PMID- 1445192 TI - Regulation of the synthesis, processing and translocation of lipoprotein lipase. PMID- 1445195 TI - Importance of the structural zinc atom for the stability of yeast alcohol dehydrogenase. AB - Yeast alcohol dehydrogenase is a tetrameric enzyme containing zinc. Initially we confirmed the presence of two zinc atoms per subunit. Incubation of the enzyme with increasing concentrations of dithiothreitol, a method for partial chelation, allowed first the reduction of four disulphide bridges per enzyme, but eventually was sufficient to chelate the structural zinc atom without having any effect on the zinc located in the active site. The enzyme activity was not affected but the enzyme became very sensitive to heat denaturation. Chelation by EDTA was also performed. Given its location at an external position in the globular protein, protected in each subunit by one disulphide bridge, the results establish that the second zinc atom present on each enzymic subunit plays a prominent conformational role, probably by stabilizing the tertiary structure of yeast alcohol dehydrogenase. Recovery experiments were performed by incubation of the native enzyme, or the dithiothreitol-treated enzyme, with a small amount of Zn2+. A stabilization effect was found when the structural zinc was re-incorporated after its removal by dithiothreitol. In all cases a large increase in activity was also observed, which was much greater than that expected based on the amount of re-incorporated zinc atom, suggesting the re-activation of some inactive commercial enzyme which had lost some of its original catalytic zinc atoms. PMID- 1445196 TI - The effect of metal ions on the activity and thermostability of the extracellular proteinase from a thermophilic Bacillus, strain EA.1. AB - The proteinase from the extremely thermophilic Bacillus strain EA.1 exhibits maximum stability at a pH of approx. 6.5. In the presence of calcium ions the half-life at 95 degrees C of the enzyme at this pH was 17 min, and loss of activity followed first-order decay kinetics. The role of metal ions in the activity and stability of the enzyme was studied using the holoenzyme, the metal depleted apoenzyme, and a zinc-enriched apoenzyme preparation. Zinc and calcium ions were the preferred bivalent cations for the active site and stabilization site(s) respectively. Stabilization by metal ions was not in itself a highly stringent process, but ions other than calcium which stabilized the enzyme generally had a concomitant inhibitory effect on activity. Inhibition and stabilization of the enzyme by cations were concentration-dependent effects and certain ions activated the apoenzyme but not the holoenzyme. Manganese(II) ions conferred some stability and also activated the enzyme, but in the latter case were not as effective as zinc ions. The results are discussed with reference to the ionic radii, co-ordination number and preferred ligand donors of the ions. Mercury(II) ions severely compromised enzyme activity and stability, and the effects of thiol-reactive agents suggest that thiol groups also have a role in enzyme integrity. PMID- 1445198 TI - Graphic analysis of relaxation times of enzyme-catalysed reactions. An extension of the graphic method of King and Altman. AB - An extension of the graphic method of King & Altman (1956) (J. Phys. Chem. 60, 1375-1378) is applied to the analysis of relaxation times of enzyme-catalysed reactions and a simple graphic method is presented. Clear-cut graphs, simple drawing, easy operation (without the need to perform the usual complex mathematical operations), and reliable results are the main characteristics of this kind of graphic method. A system of enzyme-catalysed reactions (E <--> ES <- > EP) is used as the actual example for illustrating the graphic method. PMID- 1445197 TI - Primary structure of beta s-crystallin from human lens. AB - The complete primary structure of beta s-crystallin from human lens is reported. The sequence was elucidated by automatic Edman degradation of tryptic and CNBr peptides. The blocked N-terminal dipeptide was identified by fast-atom bombardment mass spectroscopy. The sequence comparison with other members of crystallin family reveals a closer relationship to human gamma-crystallin (53% identity) than with beta A3/A1 crystallin (37% identity). The structure, evolutionary characteristics and role of beta s-crystallin in lens are discussed. PMID- 1445199 TI - Developmental regulation and neuronal expression of the mRNA of rat n-chimaerin, a p21rac GAP:cDNA sequence. AB - Human n-chimaerin is a GTPase-activating protein (GAP) for p21rac and a phorbol ester receptor. We have isolated rat n-chimaerin cDNA and investigated the cellular and developmental pattern of mRNA expression in the brain. There is extensive sequence conservation with human n-chimaerin in the coding region and the first 400 nucleotides of the 3'-untranslated region (UTR) (90% and 83% identity respectively). The rat cDNA encodes an additional 35 N-terminal amino acids compared with the reported human cDNA, which has a 5'-UTR sequence inversion and a 41-nucleotide deletion including the putative initiator methionine. The rat cDNA encodes a 334-amino acid protein (38200 M(r), pI 8.04) with 97% amino acid sequence identity with the human protein, after correction of the human 5'-DNA sequence. n-Chimaerin mRNA was detectable in embryonic rat brain at day 15 and increased in amount postnatally from birth to 20 days, coincident with cellular differentiation and synaptogenesis. n-Chimaerin mRNA is restricted to neurons, with highest concentrations in hippocampal pyramidal cells, granule cells of the dentate gyrus and cortical neurons. In the cerebellum the mRNA was detected only in Purkinje neurons. The pattern and specificity of mRNA expression suggests an important role for n-chimaerin in neuronal signal-transduction mechanisms. PMID- 1445200 TI - Characterization of an ATP-driven H+ pump in human placental brush-border membrane vesicles. AB - The presence of an ATP-driven H+ pump as measured by H+ uptake upon addition of ATP was not demonstrable in human placental brush-border membrane vesicles when used in their native form, owing to their right-side-out orientation. However, the presence of the H+ pump in these membranes became evident when the membrane vesicles were transiently exposed to 1% cholate, with subsequent removal of the detergent to re-form the vesicles. Apparently, cholate pretreatment reoriented the H+ pump from an inward-facing configuration to outward-facing. Consequently, H+ uptake in response to externally added ATP was easily demonstrable in these cholate-pretreated vesicles by using the delta pH indicator Acridine Orange. In addition, bafilomycin A1-sensitive ATPase activity was measurable in cholate pretreated vesicles, but not in native intact vesicles, indicating reorientation of the H+ pump. The reoriented H+ pump was electrogenic because H+ uptake was stimulated by an inside-negative anion-diffusion potential or when the vesicles were voltage-clamped. ATP supported H+ uptake with an apparent Km of 260 microM. ITP and GTP supported the pump activity partially, whereas CTP and UTP did not. Mg2+ and Mn2+ were the most preferred bivalent cations. Co2+ and Zn2+ showed partial activity, whereas Ca2+ and Ba2+ showed little or no activity. The pump was inhibited by nanomolar concentrations of bafilomycin A1 and micromolar concentrations of N-ethylmaleimide, p-chloromercuribenzenesulphonate, NN dicyclohexylcarbodi-imide and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, but was relatively insensitive to oligomycin, vanadate and NaN3. The inhibition by N ethylmaleimide was protectable by ATP. It is concluded that human placental brush border membranes possess an ATP-driven H+ pump and that, on the basis of its characteristics, it belongs to the class of vacuolar (V-type) H+ pumps. PMID- 1445201 TI - Differential uptake of [3H]guanosine by nucleoside transporter subtypes in Ehrlich ascites tumour cells. AB - Intracellular metabolism of [3H]guanosine was minimal (< 15%) during the first 22 s of incubation, and hence reasonable estimates of initial-rate influx kinetics could be derived by using metabolically active cells. Na(+)-dependent concentrative [3H]guanosine uptake was not observed. Data suggest that [3H]guanosine was accumulated primarily via the nitrobenzylthioguanosine (NBTGR) sensitive subtype of facilitated nucleoside transporter. Incubation of cells with 100 nM-NBTGR significantly decreased the potency of guanosine as an inhibitor of [3H]uridine influx. The Vmax. for [3H]guanosine influx (9.2 pmol/s per microliters) was significantly lower than that for [3H]uridine influx (16 pmol/s per microliters). The Km for transporter-mediated [3H]guanosine influx determined in the presence of 100 nM-NBTGR was 16-fold higher (1780 microM) than that determined in its absence, whereas the Km for [3H]uridine influx was shifted by only 2-fold. In other respects, the cellular accumulations of [3H]guanosine and [3H]uridine were similar; both had Km values of approx. 140 microM for total mediated influx, and both were inhibited similarly by other nucleosides and transport inhibitors. These characteristics, and the fact that guanosine is an endogenous nucleoside, suggest that [3H]guanosine may prove useful as a poorly metabolized, relatively selective, substrate for study of the NBTGR-sensitive nucleoside transport systems of mammalian cells. PMID- 1445202 TI - Evidence for lithium-sensitive inositol 4,5-bisphosphate accumulation in muscarinic cholinoceptor-stimulated cerebral-cortex slices. AB - Stimulation of [3H]inositol-prelabelled rat cerebral-cortex slices with carbachol results in the accumulation of four [3H]inositol bisphosphate isomeric species, Ins(1,3)P2, Ins(1,4)P2, Ins(3,4)P2 and Ins(4,5)P2. Although the last isomer ran as a minor peak on h.p.l.c., its accumulation was dramatically enhanced in the presence of Li+ (1 mM), such that at 30 min it represented almost 35% of the total bisphosphate fraction. The accumulation of Ins(4,5)P2 appeared to be very sensitive to Li+ (EC50 = 94 +/- 3 microM), strongly implicating a Li(+)-sensitive metabolism. Evidence for this is provided from the rapid but Li(+)-sensitive decay of Ins(4,5)P2 when muscarinic-receptor stimulation is antagonized by atropine at a time when accumulations have reached a new steady state. Manipulation of phospholipase D by activators and inhibitors of protein kinase C did not suggest a role for phospholipase D hydrolysis of PtdInsP2 in the formation of Ins(4,5)P2. Attempts to reveal Ins(4,5)P2 metabolism, or indeed its synthesis from Ins(1,4,5)P3, were not successful with broken cell preparations and strongly suggest discrete compartmentation of inositol phosphate metabolism in the intact cell. PMID- 1445203 TI - Characterization of a Gi-protein from Trypanosoma cruzi epimastigote membranes. AB - A guanosine 5'-[gamma-[35S]thio]triphosphate-binding activity was detergent extracted from Trypanosoma cruzi membranes. This binding activity was co-eluted from gel-filtration columns with a factor which, in a heterologous reconstitution system, blocks glucagon stimulation of adenylate cyclase activity in liver membranes. ADP-ribosylation of these membranes by pertussis toxin eliminated this blocking capacity. Incubation of T. cruzi membranes with activated pertussis toxin and [adenylate-32P]NAD+ led to the incorporation of radioactivity into a labelled product with an apparent M(r) of approx. 43,000. Crude membranes were electrophoresed on SDS/polyacrylamide gels and analysed, by Western blotting, with GA/1 anti-alpha common, AS/7 anti-alpha t, anti-alpha i1 and anti-alpha i2 polyclonal antibodies. These procedures led to the identification of a specific polypeptide band of about 43 kDa. Another polypeptide reacting with the SW/1 anti beta antibody, of about 30 kDa, was also detected in the membrane fraction. PMID- 1445204 TI - A model for adenosine transport and metabolism. AB - 1. A model is presented for adenosine transport and metabolism in different steady states. The model considers steady-state equations for metabolic enzymes based on information from the literature on their kinetic behaviour. 2. Assuming that extracellular adenosine and inosine are translocated by three transporters, we have devised rate equations for these nucleoside transporters which are valid when both nucleosides are present. Since the Na(+)-independent transporter can either incorporate nucleosides into the cell or release them, various conditions have been simulated in which inosine was either incorporated or released. 3. Control analyses are reported which show that the fluxes towards intracellular adenine nucleosides are controlled by ecto-5'-nucleotidase in some circumstances and by the nucleoside transporters in others. The nucleoside transporter is responsible for five fluxes (two Na+ dependent adenosine transport mechanisms, a Na(+)-dependent inosine transport, a Na(+)-independent adenosine transport and a Na(+)-independent inosine influx or efflux) but the control is not always positive for all these fluxes. The control patterns of these five fluxes indicate that, in the presence of extracellular adenosine and inosine, the intracellular metabolism of adenine derivatives would be highly dependent on the extracellular and intracellular concentrations of both nucleosides, on the ectoenzymes (5' nucleotidase and adenosine deaminase) and on the transporter. 4. Predictions of the model were examined. The results indicate that a change in one independent variable (extracellular AMP concentration) makes the system evolve towards a new steady state which is far from the initial one and has a different control pattern. In contrast, simulation of inhibition of the carriers produces only slight modification of the fluxes since the concentrations of the metabolites change to counteract the effect. Thus, for instance, a 50% inhibition of the three carriers does not affect the flux towards intracellular adenine nucleotides. Finally, our model has confirmed that the evolution of the concentration of extracellular adenosine, when an increase in extracellular AMP is produced, agrees with the behaviour expected for a neurohormone. PMID- 1445205 TI - A strategy for increasing an in vivo flux by genetic manipulations. The tryptophan system of yeast. AB - Decreases in enzyme activity often have little effect on the flux carried by the pathway. Similarly, up-modulation of single genes, and hence of the dependent enzyme concentrations, is frequently found to be ineffective in increasing the flux in the pathway in which the enzyme occurs. This insensitivity to enzyme variation is demonstrated experimentally for five separate enzymes in the tryptophan synthesis system of yeast, first by down-modulation of the gene dose and secondly by increasing the dose using multi-copy vectors. Such a lack of response is discussed in terms of the concepts of metabolic control analysis. When these five enzymes, however, were simultaneously increased by a multi-copy vector carrying all five genes, a substantial elevation of the flux to tryptophan was observed. These findings revealed a new phenomenon, namely the more than additive effects on the flux of simultaneous elevations of several enzyme activities. PMID- 1445206 TI - Determining stability of proteins from guanidinium chloride transition curves. AB - The guanidinium chloride (GdmCl) denaturation of RNAase A, lysozyme and metmyoglobin was investigated at several pH values by using absorbance measurements at 287, 300 and 409 nm respectively. From these measurements the free-energy change on denaturation, delta Gapp., was calculated, assuming a two state mechanism, and values of delta Gapp. at zero concentration of the denaturant were measured. For each protein all delta Gapp. values were adjusted to pH 7.00 by using the appropriate relationship between delta Gapp. and pH. Dependence of the adjusted delta Gapp. value on GdmCl concentration increases for metmyoglobin and decreases for the other two proteins as the denaturant concentration decreases. It has been shown that these are expected results if the presence of the acid-denatured state during the GdmCl denaturation of proteins is considered. PMID- 1445207 TI - Overexpression, purification and characterization of the Escherichia coli MelR transcription activator protein. AB - The gene encoding Escherichia coli MelR protein has been cloned in the expression vector pJLA502. MelR has been overexpressed, substantially purified and shown to bind to DNA fragments carrying the melAB promoter. A truncated version of the melR gene, encoding the C-terminal half of MelR, was also cloned into pJLA502; the protein product of this truncated gene binds to the melAB promoter but was not overproduced. A number of amino acid substitutions were made in the recognition helices of two putative helix-turn-helix motifs in the C-terminal part of MelR, and the effects of these mutations on MelR-dependent transcription initiation at the melAB promoter have been measured. PMID- 1445208 TI - Studies on the binding of the Escherichia coli MelR transcription activator protein to operator sequences at the MelAB promoter. AB - Escherichia coli MelR protein binds to two sites located upstream of the melAB transcription start site. Although both sites are required for optimal melibiose dependent expression from the melAB promoter, some MelR-dependent expression is found if the upstream site is deleted or if the spacing between the two sites is altered. Gel retardation assays have been exploited to study MelR binding to a DNA fragment carrying just the upstream site. Methylation interference analysis was used to identify one guanine (at -104) which is important for MelR binding. Mutational analysis confirmed the importance of this base and revealed a second position (at -110) where mutations interfere with melAB promoter activity. Experiments using potassium permanganate as a probe suggested that the DNA sequence around -110 adopts a distorted conformation. We propose that the mutation at -104 alters MelR binding by interfering with a direct contact, whereas the mutation at -110 primarily affects DNA conformation. The binding of purified MelR protein to a melAB promoter fragment carrying both binding sites has also been studied: binding results in four retarded bands in gel assays. Methylation interference experiments have been exploited to identify the binding sites occupied in each complex. Although both binding sites share a common 18 bp sequence, MelR binding to the more upstream site is stronger. We could find no evidence for co-operative interactions between MelR and RNA polymerase and no major effects of melibiose. Some evidence for melibiose-dependent distortion in complexes between MelR and the melAB promoter is discussed. PMID- 1445209 TI - Iron and aluminium in relation to brain ferritin in normal individuals and Alzheimer's-disease and chronic renal-dialysis patients. AB - Ferritin has been isolated and its subunit composition, iron and aluminium content determined in the cerebral cortex and cerebellum of normal individuals and in the cerebral cortex of Alzheimer's-disease and renal-dialysis patients. An e.l.i.s.a. for ferritin has been developed and the ferritin, non-haem iron and aluminium content of the parietal cortex were determined in normal individuals and Alzheimer's-disease patients. It was found that ferritin from the cerebral cortex and cerebellum of normal individuals had a high H-subunit content, similar to that of heart ferritin. The subunit composition of ferritin isolated from the cerebral cortex was not significantly altered in Alzheimer's-disease or renal dialysis patients. Ferritin from the cerebral cortex of normal individuals had only approx. 1500 atoms of iron per molecule and the iron content of ferritin was not significantly changed in Alzheimer's-disease or renal-dialysis patients. Ferritin isolated from the cerebral cortex of normal, Alzheimer's-disease and renal-dialysis patients had less than 9 atoms of aluminium per molecule. The failure to find increased concentrations of aluminium associated with ferritin in dialysis patients, who had markedly increased concentrations of aluminium in the cerebral cortex, shows that aluminium does not accumulate in ferritin in vivo. This has important implications for the toxicity of aluminium, since it implies that cells are unable to detoxify aluminium by the same mechanism as that available for iron. Comparison of the concentrations of ferritin, aluminium and iron in the parietal cortex from normal and Alzheimer's-disease patients showed that, whereas the concentration of aluminium was not increased, both ferritin and iron were significantly increased in Alzheimer's disease. PMID- 1445210 TI - Interaction of aluminium citrate with horse spleen ferritin. AB - Horse spleen ferritin was found to bind aluminium poorly after equilibrium dialysis with buffered aluminium citrate solutions. Not more than 10 aluminium atoms/ferritin molecule were bound from a 25 microM-aluminium solution, pH 7.4, and the degree of binding was dependent on the method used to prepare the aluminium citrate solution. Up to 120 aluminium atoms/molecule were bound when ferritin iron cores were reconstituted by the addition of 3000 Fe atoms to apoferritin in the presence of aluminium citrate. Comparison of previously published binding constants of ferritin and citrate for aluminium suggests that, in the cell, the prevalence of small ligands effectively prevents the association of large amounts of aluminium with ferritin. PMID- 1445211 TI - Bivalent-metal binding to CheY protein. Effect on protein conformation. AB - CheY is a 14 kDa cytoplasmic protein that is activated by the transfer of a phosphoryl moiety to Asp-57 from phosphoCheA during signal transduction in bacterial chemotaxis. It has been established that metal ions are necessary for the autophosphorylation of CheA, the transfer of phosphate from phosphoCheA to CheY and the autodephosphorylation of phosphoCheY. In this work, paramagnetic relaxation enhancement has been used in conjunction with one- and two-dimensional n.m.r. to study the interaction of CheY with bivalent metal ions. These studies have led to the discovery of two conformations of the protein in water, corresponding to the metal-free and the metal-bound states. Binding of bivalent cations like Mg2+, Ca2+, Sr2+, Zn2+ and Mn2+ results in a conformational change from the metal-free to the metal-bound state. Preliminary assignments of the aromatic proton resonances are reported. Comparison of phase-sensitive double quantum-filtered COSY, homonuclear Hartmann-Hahn coherence transfer and nuclear Overhauser enhancement spectra from the metal-bound and metal-free protein indicates that Trp-58, Thr-87 and Tyr-106 are particularly affected by the conformational change involved, and that this change is limited to a small number of residues. In addition, homonuclear Hartmann-Hahn coherence transfer experiments with paramagnetic Mn2+ show significant suppression of cross-peaks associated with Trp-58 and several neighbouring residues. Comparison of the distances estimated using n.m.r. with the CheY crystal structure indicates that the n.m.r. results are consistent with bivalent metal binding at the cluster of aspartic acid residues that includes Asp-13 and Asp-57. These studies also demonstrate the utility of paramagnetic metal-induced relaxation in conjunction with two-dimensional n.m.r. measurements for exploring ligand-binding sites. PMID- 1445212 TI - Activation of the GTP-binding protein Gq by rhodopsin in squid photoreceptors. AB - Photoaffinity labelling by a GTP analogue has been used to identify a 42 kDa band as the major G alpha subunit in squid photoreceptor membranes, recently identified by partial sequence analysis to be a member of the Gq sub-group of GTP binding proteins [Pottinger, Ryba, Keen & Findlay (1991) Biochem. J. 279, 323 326]. Guanine-nucleotide-binding displacement analysis gave a stoichiometry of 1 G-protein per 12.5 rhodopsin molecules, the same as in vertebrate rod photoreceptors. Binding was not detected above background in the dark, but was rapidly activated by light. Unlike vertebrate transducin, this G-protein is very temperature-sensitive. GTP binding is maximal at temperatures less than 10 degrees C and is much decreased after several minutes above 18 degrees C. The light-stimulated GTPase rate is maximal around 10 degrees C, above which the loss of binding sites counteracts the increase in hydrolytic rate per site. Earlier studies described light-sensitive G alpha components of 40 and 45 kDa, by ADP ribosylation in the presence of cholera and pertussis toxins. These are now shown to be very minor components, as the prolonged treatment at elevated temperature required for ADP-ribosylation is sufficient to inactivate the major G alpha totally. Unlike the minor G alpha components, the 42 kDa G alpha is not inhibited by Ca2+. PMID- 1445213 TI - Expression of transfected stathmin cDNA reveals novel phosphorylated forms associated with developmental and functional cell regulation. AB - Stathmin is a ubiquitous, highly conserved phosphoprotein, which most likely acts as an intracellular relay integrating various transduction pathways triggered by extracellular signals. Two post-translational isoforms (alpha and beta) have been previously identified whose increasingly phosphorylated forms migrate as a set of isoelectric variant spots (molecular mass 19 kDa; pI 6.2-5.6) on two-dimensional electrophoretic gels. In parallel with the phosphorylation of these forms of stathmin, two sets of three proteins migrating with slightly higher apparent molecular masses (21 and 23 kDa respectively) also incorporated radioactive phosphate in response to cell regulation through various transduction pathways. These phosphoproteins, previously referred to as proteins '16' and '17', share several biochemical properties with stathmin and are recognized by antibodies directed to stathmin or to stathmin peptides. Furthermore, when rat stathmin cDNA was transfected into mouse myogenic C2 cells, it directed the expression of protein sets 16 and 17 together with the 19 kDa forms of stathmin, as detected with a species-specific anti-stathmin antiserum. Proteins 16 and 17 are thus novel phosphorylated derivatives of stathmin, encoded by the same cDNA as its previously identified 19 kDa forms. These results increase the known complexity and diversity of stathmin patterns, which may yield the molecular support for its proposed role as a relay integrating various signals which regulate the proliferation, differentiation and functions of cells during development and adult life. PMID- 1445214 TI - Interaction of GTPase-activating protein with p21ras, measured using a continuous assay for inorganic phosphate release. AB - The mechanism of GTPase-activating protein (GAP) activation of p21ras GTP hydrolysis has been investigated by measuring the kinetics of release of Pi during the hydrolysis. The measurement uses a continuous spectroscopic assay for Pi, based on a guanosine analogue, 2-amino-6-mercapto-7-methylpurine ribonucleoside, as substrate for purine nucleoside phosphorylase [Webb, M.R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4884-4887]. This phosphorolysis gives an absorbance increase at 360 nm, so that when the reaction is coupled to GTP hydrolysis, the change in absorbance gives the total amount of Pi released from the p21ras. The rate of the absorbance increase gives the GTPase activity. This provides a non-radioactive method of determining p21ras concentration and GAP activity. It was used to determine the interaction of GAP with wild-type p21ras and two mutants (Leu-61/Ser-186 and Asp-12), all in the GTP (or guanosine 5'-[ beta gamma-imido]triphosphate) form. The Leu-61/Ser-186 mutant binds 10-fold tighter than does the wild-type protein. The Asp-12 mutant binds to GAP with the same affinity as the wild-type protein. A novel GTPase activity was characterized whereby the EDTA-induced nucleotide release and GAP-activated cleavage of bound GTP leads to steady-state turnover of GTP hydrolysis. An assay for GAP is described based on this activity. PMID- 1445215 TI - A Raman study of the binding of Fe(III) to ATP and AMP. AB - ATP-Fe and AMP-Fe complexes in water (H2O and 2H2O) at pH 7.5 were studied using Raman spectroscopy. Parallel and perpendicular polarization spectra were recorded in the spectral range 200-1650 cm-1, and the depolarization ratios for most of the bands were calculated. The changes in the frequencies, intensities and depolarization ratios of the ATP and AMP bands after the addition of FeCl3 showed that the adenine moiety, in addition to the phosphate(s), was involved in the binding of Fe to both ATP and AMP. Direct interactions of Fe(III) with the phosphate chain and the N-7 nitrogen and indirect interaction (via water molecules) with the amide group were proposed for the ATP-Fe complex. In contrast, direct interaction with the phosphate group and indirect interaction with the amide group were observed for the AMP-Fe complex. The different interactions of the two complexes suggest an 'anti' conformation for the ATP-Fe complex and a 'syn' conformation for the AMP-Fe complex. The strong binding of Fe to ATP compared with AMP and the difference in the conformation of the ATP-Fe and the AMP-Fe complexes may be significant in the pathway of Fe release in mitochondria. PMID- 1445216 TI - Kinetics of the monomer-dimer reaction of yeast hexokinase PI. AB - Kinetic studies of the glucose-dependent monomer-dimer reaction of yeast hexokinase PI at pH 8.0 in the presence of 0.1 M-KCl have been carried out using the fluorescence temperature-jump technique. A slow-relaxation effect was observed which was attributed from its dependence on enzyme concentration to the monomer-dimer reaction; the reciprocal relaxation times tau-1 varied from 3 s-1 at low concentrations of glucose to 42 s-1 at saturating concentrations. Rate constants for association (kass.) and dissociation (kdiss.) were determined as a function of glucose concentration using values of the equilibrium association constant of the monomer-dimer reaction derived from sedimentation ultracentrifugation studies under similar conditions, and also from the dependence of tau-2 on enzyme concentration. kass. was almost independent of glucose concentration and its value (2 x 10(5) M-1.s-1) was close to that expected for a diffusion-controlled process. The influence of glucose on the monomer-dimer reaction is entirely due to effects on kdiss., which increases from 0.21 s-1 in the absence of glucose to 25 s-1 at saturating concentrations. The monomer and dimer forms of hexokinase have different affinities and Km values for glucose, and the results reported here imply that there may be a significant lag in the response of the monomer-dimer reaction to changes in glucose concentrations in vivo with consequent hysteretic effects on the hexokinase activity. PMID- 1445217 TI - Purification and characterization of a diptericin homologue from Sarcophaga peregrina (flesh fly). AB - A protein with a molecular mass of 8 kDa was found to be synthesized specifically when the fat-body from injured Sarcophaga peregrina larvae was cultured in vitro. This protein was purified from the haemolymph of the injured larvae to near homogeneity. Partial amino acid sequencing revealed that this protein is a diptericin homologue. It showed bactericidal activity on growing, but not resting Escherichia coli cells. E. coli cells become elongated on treatment with this protein. PMID- 1445218 TI - Identification of calreticulin isoforms in the central nervous system. AB - In the present paper we report the cloning and sequencing of the cDNA encoding two calreticulin isoforms from Xenopus laevis central nervous system. The two isoforms display 93% identity at the amino acid level. The predicted amino acid sequences of the amphibian calreticulins are very similar (76%) to those of mammalian liver and skeletal muscle. Xenopus laevis calreticulins are characterized by a very acidic c-terminal domain endowed with the endoplasmic reticulum retention signal KDEL. The cDNAs of both clones encode an N glycosylation consensus sequence. A third clone of calreticulin was also identified. The restriction map of this clone was clearly distinct from that of the two sequenced clones. These results indicate the existence of multiple calreticulin isoforms in the central nervous system and open questions about their functional role in different cells and/or subcellular compartments. PMID- 1445219 TI - Mechanisms of thermoinactivation of endoglucanase I from Trichoderma reesei QM 9414. AB - The mechanism of irreversible thermoinactivation of endoglucanase I from Trichoderma reesei has been determined at 70 degrees C at the pH of maximum enzyme activity. The time-course of thermoinactivation did not follow first-order kinetics and kinetic constants of the process were dependent on enzyme concentration, suggesting that aggregation was the main process leading to irreversible inactivation. The enzyme was extremely resistant to urea, which in fact seemed to stabilize it against temperature. Disulphide exchange, deamidation and hydrolysis of peptide bonds were also responsible for the loss of enzyme activity at 70 degrees C. PMID- 1445220 TI - Production and interferon-gamma-mediated regulation of complement component C2 and factors B and D by the astroglioma cell line U105-MG. AB - In this paper, we demonstrate the synthesis of the complement component C2 and factors B and D by the human astroglioma cell line U105-MG. All three components were structurally and antigenically similar to their serum counterparts, as determined by biosynthetic labelling studies or Western blot analysis. Northern blot analysis demonstrated that the mRNAs of all three components had the same apparent sizes as the equivalent mRNAs from hepatocyte and monocyte cell lines. Interestingly, U105-MG cells produce two C2 transcripts with sizes of approximately 2.8 and 2.3 kb. Interferon-gamma (IFN-gamma) enhanced the expression of C2 and factor B mRNA and protein in a dose- and time-dependent fashion, while factor D expression was refractory to IFN-gamma. IFN-gamma appeared to predominantly enhance the expression of the large (2.8 kb) C2 transcript. Kinetic studies demonstrated peak C2 and factor B expression in 48 h in response to IFN-gamma, similar to the acute-phase response of factor B in serum. These data are the first to demonstrate the synthesis of C2 and factor D by astroglioma cells. Combined with previous reports documenting the synthesis of C3 by astrocytes, our data suggest that endogenous synthesis of complement proteins, and particularly of alternative pathway activation components (C3, factors B and D), may play an important role in host defence in the central nervous system. PMID- 1445221 TI - Overproduction of the pyruvate dehydrogenase multienzyme complex of Escherichia coli and site-directed substitutions in the E1p and E2p subunits. AB - The aceEF-lpd operon of Escherichia coli encodes the pyruvate dehydrogenase (E1p), dihydrolipoamide acetyltransferase (E2p) and dihydrolipoamide dehydrogenase (E3) subunits of the pyruvate dehydrogenase multienzyme complex (PDH complex). An isopropyl beta-D-thiogalactopyranoside-inducible expression system was developed for amplifying fully lipoylated wild-type and mutant PDH complexes to over 30% of soluble protein. The extent of lipoylation was related to the degree of aeration during amplification. The specific activities of the isolated PDH complexes and the E1p component were 50-75% of the values normally observed for the unamplified complex. This could be due to altered stoichiometries of the overproduced complexes (higher E3 and lower E1p contents) or inactivation of E1p. The chaperonin, GroEL, was identified as a contaminant which copurifies with the complex. Site-directed substitutions of an invariant glycine residue (G231A, G231S and G231M) in the putative thiamine pyrophosphate binding fold of the E1p component had no effect on the production of high molecular-mass PDH complexes but their E1p and PDH complex activities were very low or undetectable, indicating that G231 is essential for the structural or catalytic integrity of E1p. A minor correction to the nucleotide sequence, which leads to the insertion of an isoleucine residue immediately after residue 273, was made. Substitution of the conserved histidine and arginine residues (H602 and R603) in the putative active-site motif of the E2p subunit confirmed that H602 of the E. coli E2p is essential, whereas R603 could be replaced without inactivating E2p. Deletions affecting putative secondary structural elements at the boundary of the E2p catalytic domain inhibited catalytic activity without affecting the assembly of the E2p core or its ability to bind E1p, indicating that the latter functions are determined elsewhere in the domain. The results further consolidate the view that chloramphenicol acetyltransferase serves as a useful structural and functional model for the catalytic domain of the lipoate acyltransferases. PMID- 1445222 TI - Involvement of caldesmon at the actin-myosin interface. AB - Addition of myosin subfragment 1 (S-1) to the actin-caldesmon binary complex, which forms bundles of actin filaments resulted in the formation of actin/caldesmon-decorated filaments [Harricane, Bonet-Kerrache, Cavadore & Mornet (1991) Eur. J. Biochem. 196, 219-224]. The present data provide further evidence that caldesmon and S-1 compete for a common actin-binding region and demonstrate that a change occurs in the actin-myosin interface induced by caldesmon. S-1 digested by trypsin, which has an actin affinity 100-fold weaker than that of native S-1, was efficiently removed from actin by caldesmon, but not completely dissociated. This particular ternary complex was stabilized by chemical cross linking with carbodi-imide, which does not have any spacer arm, and revealed contact interfaces between the different protein components. Cross-linking experiments showed that the presence of caldesmon had no effect on stabilization of actin-(20 kDa domain), whereas the actin-(50 kDa domain) covalent association was significantly decreased, to the point of being virtually abolished. PMID- 1445223 TI - Structural features of the low-molecular-mass human salivary mucin. AB - The low-molecular-mass human salivary mucin has at least two isoforms, MG2a and MG2b, that differ primarily in their sialic acid and fucose content. In this study, we characterize further these isoforms, particularly their peptide moieties. Trypsin digests of MG2a and MG2b yielded high- and low-molecular-mass glycopeptides following gel filtration on Sephacryl S-300. The larger glycopeptides from MG2a and MG2b had similar amino acid compositions and identical N-terminal sequences, suggesting common structural features between their peptides. An oligonucleotide probe generated from the amino acid sequence of the smaller glycopeptide from MG2a was employed in Northern-blot analysis. This probe specifically hybridized to two mRNA species from human submandibular and sublingual glands. A cDNA clone selected from a human submandibular gland cDNA expression library with antibody generated against deglycosylated MG2a also hybridized to these two mRNA species. In both cases, the larger mRNA was polydisperse, and the hybridization signal was more intense in the sublingual gland. In addition, the N-terminal amino acid sequence of the larger glycopeptide was found to be part of one of the selected MG2 cDNA clones. PMID- 1445224 TI - Cellular distribution of nuclear factor kappa B binding activity in rat liver. AB - The cellular localization of nuclear factor kappa B (NF-kappa B) binding activity in rat liver has been investigated using electrophoretic mobility shift assay on extracts of highly purified hepatocytes and Kupffer cells obtained from liver perfused in vivo with collagenase. Constitutive NF-kappa B binding activity was demonstrated in nuclear extracts of control Kupffer cells, and this was not apparently influenced by injection of lipopolysaccharide (LPS) into rats 24 h before perfusion. In contrast, little nuclear NF-kappa B binding activity was present in hepatocytes from control animals, although there was detectable inactive, inhibitor-bound, NF-kappa B in the cytoplasm. However, nuclear NF-kappa B binding activity was increased in hepatocytes from LPS-treated animals and after in vitro culture of control rat hepatocytes. Thus NF-kappa B binding activity has been demonstrated in highly purified hepatocytes and appears to be inducible both in vivo and in vitro. These findings support a role for NF-kappa B in hepatocyte gene regulation which may be important in the modulation of the hepatic acute phase response. PMID- 1445225 TI - Characteristics of phosphorylated and non-phosphorylated dentine phosphoprotein. AB - Heterogeneity among the odontoblast-specific, highly phosphorylated acidic protein dentine phosphoprotein (DPP) obtained from different species has been reported by several investigators. In the present study, the apparent molecular mass variations in rabbit and mouse DPP were investigated. Extracellular matrix (ECM) DPPs were isolated and characterized. Primary gene products, before post translational phosphorylation, were analysed based upon translation products produced in a rabbit reticulocyte lysate cell-free system using a polyclonal mouse anti-DPP antibody. Nascent non-phosphorylated DPPs were also identified from intracellular protein extracts. Mouse and rabbit ECM phosphoproteins exhibited a 10 kDa difference in size. However, nascent intracellular or translation products from both species showed the same lower molecular mass (approx. 45 kDa). Furthermore, Northern-blot analysis showed a single mRNA of the same size in both species (approx. 1.6 kb) which contains information for a protein no larger than 50 kDa. Our results indicate that the difference in molecular mass (or electrophoretic behaviour) among DPPs from different species is due to post-translational modifications, in this case phosphorylation. PMID- 1445226 TI - Lysosomal cysteine endopeptidases mediate interleukin 1-stimulated cartilage proteoglycan degradation. AB - The peptidyl diazomethane inactivator of cysteine endopeptidases, benzyloxycarbonyl-Tyr-Ala-CHN2, was tested as an inhibitor of interleukin 1 alpha stimulated release of proteoglycan from bovine nasal septum cartilage explants. Like the previously tested epoxidyl peptide proinhibitor trans-epoxysuccinyl leucylamido-(3-methyl)butane ethyl ester, it proved to be an effective inhibitor of proteoglycan release from cartilage, with significant inhibition at a concentration of 1 microM. The inhibition did not seem to be due to a general toxic effect. The rates of inactivation of the bovine cysteine endopeptidases by the peptidyl diazomethane, the epoxidyl peptide proinhibitor and its active form were determined. Benzyloxycarbonyl-Tyr-Ala-CHN2 proved to be a rapid inactivator of cathepsins L, S and B, but reacted much more slowly with cathepsin H and calpain. Thus it would appear that the latter two enzymes are not implicated in proteoglycan release in our test system. The peptidyl diazomethane and epoxidyl peptide proinhibitor (above) were also tested for their effects on three other interleukin 1-mediated cellular events, namely epidermal growth factor receptor transmodulation, and interleukin 6 and prostaglandin E2 production. In all cases the inactivators did not interfere with the response to interleukin 1 in human gingival fibroblasts. We conclude that one or more of the lysosomal cysteine endopeptidases cathepsins B, L and S mediate interleukin 1-stimulated cartilage proteoglycan degradation without affecting signal transduction. PMID- 1445227 TI - Hirulog-1 and -B2 thrombin specificity. PMID- 1445228 TI - Fluorescence of peptide N-terminal 2-oxoacyl and quinoxaline derivatives. AB - A peptide reacts with glyoxalic acid resulting in transamination of the N terminal residue to form a 2-oxoacyl group. This further reacts with o phenylenediamine, leading to a quinoxaline derivative of the original N-terminal amino acid, which is cleavable in mild acid [Dixon & Fields (1972) Methods Enzymol. 25, 409-419]. The 2-oxoacyl peptides are weakly fluorescent with emission maxima around 410 nm and excitation maxima at about 320 nm, depending on the nature and length of the peptide. Formation of the quinoxaline derivative results in a marked increase of fluorescence, with emission maximum of 363 nm when excited at 303 nm. The fluorescence properties of these derivatives change with the nature and length of the peptides and are affected by the presence of organic solvents, NaCl and denaturants. It is suggested that such fluorescent derivatives could be used as probes for the study of the conformation of the N terminal region of peptides and proteins. PMID- 1445229 TI - Bicarbonate-dependent ATP cleavage catalysed by pyruvate carboxylase in the absence of pyruvate. AB - Preparations of pyruvate carboxylase catalyse the cleavage of MgATP in the absence of pyruvate and acetyl-CoA. The rate of this cleavage is higher in the presence of HCO3- than in its absence. Incubation of the enzyme preparations with an excess of the pyruvate carboxylase inhibitor, avidin, completely abolishes the pyruvate carboxylating activity of the enzyme preparations but only abolishes the HCO3(-)-dependent MgATP cleaving activity, with no effect on the HCO3(-) independent ATPase activity. The HCO3(-)-dependent MgATP cleavage is also sensitive to inhibition by a pyruvate carboxylase inhibitor, oxamate, and the dependence of the reaction on the free Mg2+ concentration is similar to that of the pyruvate-carboxylation reaction, whereas the HCO3(-)-independent MgATP cleavage is not dependent on the concentration of free Mg2+ in the range tested. This indicates that MgATP cleavage by pyruvate carboxylase is entirely dependent on the presence of HCO3- and that there may be a low level of ATPase contamination in the enzyme preparations. In addition, inhibition of the HCO3(-) dependent MgATP cleavage by both avidin and oxamate indicate that although biotin does not directly participate in the reaction, its presence is required in that part of the active site of the enzyme. The rate of HCO3(-)-dependent MgATP cleavage is about 0.07% of that of the full pyruvate carboxylation reaction under similar conditions with saturating substrates. The reaction mechanism is sequential with respect to MgATP and HCO3- addition and Mg2+ adds at equilibrium before MgATP. Acetyl-CoA stimulates the HCO3(-)-dependent MgATP cleavage at low MgATP concentrations, with the stimulation being greater at low Mg2+ concentrations. At high levels of MgATP in the presence of acetyl-CoA, substrate inhibition is evident and is more pronounced at increasing concentrations of Mg2+. This inhibition appears to be, at least in part, caused by inhibition of decarboxylation of the enzyme-carboxybiotin complex by the binding to this complex of Mg2+ and MgATP, which probably act to reduce the rate of movement of carboxybiotin from the site of the MgATP cleavage reaction to that of the pyruvate carboxylation reaction where it is unstable and decarboxylates. PMID- 1445231 TI - Tissue distribution of mRNA for heparin-binding epidermal growth factor. AB - Heparin-binding epidermal growth factor (HB-EGF) is a recently identified member of the EGF family. Mature HB-EGF is processed from a larger transmembrane precursor which can itself act as a cell-surface receptor for the internalization of diphtheria toxin into eukaryotic cells. However, to date there is no information available on the distribution of HB-EGF in mammalian tissues. We have therefore used reverse-transcription PCR to analyse the expression of HB-EGF mRNA in a wide range of tissues. HB-EGF transcripts were detected in RNA isolated from 15 of the 22 tissues obtained from adult pigs, which is consistent with the ability of diphtheria toxin to affect many body tissues. PMID- 1445232 TI - Investigation of the first step of biotin biosynthesis in Bacillus sphaericus. Purification and characterization of the pimeloyl-CoA synthase, and uptake of pimelate. AB - The pimeloyl-CoA synthase from Bacillus sphaericus has been purified to homogeneity from an overproducing strain of Escherichia coli. The purification yielded milligram quantities of the synthase with a specific activity of 1 unit/mg of protein. Analysis of the products showed that this enzyme catalysed the transformation of pimelate into pimeloyl-CoA with concomitant hydrolysis of ATP to AMP. Using a continuous spectrophotometric assay, we have examined the catalytic properties of the pure enzyme. The pH profile under Vmax. conditions showed a maximum around 8.5. Apparent Km values for pimelate, CoASH, ATP.Mg2- and Mg2+ were respectively 145 microM, 33 microM, 170 microM and 2.3 mM. The enzyme was inhibited by Mg2+ above 10 mM. This acid-CoA ligase exhibited a very sharp substrate specificity, e.g. neither GTP nor pimelate analogues (di- or mono carboxylic acids) were processed. The bivalent metal ion requirement was also investigated: Mn2+ (73%) and Co2+ (32%) but not Ca2+ could replace Mg2+. The enzyme was inhibited by metal chelators such as 1,10-phenanthroline and EDTA. The synthase was a homodimer with a 28,000-M(r) subunit. N-Terminal sequencing definitely proved that this enzyme was encoded by the bioW gene. A careful study of pimelate uptake by B. sphaericus, E. coli and Pseudomonas dentrificans showed that this metabolite crossed the membrane of these microorganisms by passive diffusion, ruling out the involvement of the bioX gene product as pimelate carrier. PMID- 1445230 TI - Molecular structures of glycoprotein hormones and functions of their carbohydrate components. PMID- 1445233 TI - Exocytosis in electropermeabilized neutrophils. Responsiveness to calcium and guanosine 5'-[gamma-thio]triphosphate. AB - Electropermeabilized neutrophils were used to study the exocytotic response in rabbit neutrophils. Enzyme release from electropermeabilized neutrophils could be induced by elevating the Ca2+ concentration. Ca(2+)-induced secretion was significantly enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP[S]) in a concentration-dependent manner. The effect of GTP[S] could be blocked by guanosine 5'-[beta-thio]diphosphate (GDP[S]) and was not affected by pertussis toxin. GTP[S] did not induce enzyme release in the absence of Ca2+. Induction of an exocytotic response did not require addition of ATP. However, neutrophils permeabilized in the absence of ATP became refractory to stimulation due to a reduction in their affinity for Ca2+. Responsiveness to the effectors Ca2+ or Ca2+ + GTP[S] could be prolonged or restored by ATP. ATP was not the only agent that prolonged responsiveness; other nucleotides and inorganic phosphates were also effective. The protein kinase C inhibitors staurosporine and 1-O-hexadecyl-2 methyl-sn-glycerol did not inhibit exocytosis and had only a small effect on the prolongation and restoration of responsiveness by ATP. A hypothesis is presented suggesting that the loss of responsiveness is caused by dephosphorylation and that the restoration or prolongation of responsiveness is not mediated by protein kinase C. It is possible that an as yet unidentified Ca(2+)-binding protein is dephosphorylated, resulting in a decrease in Ca2+ affinity. PMID- 1445234 TI - Secretion of 72 kDa type IV collagenase/gelatinase by cultured human lipocytes. Analysis of gene expression, protein synthesis and proteinase activity. AB - The matrix metalloproteinases play an important role in matrix degradation, but there is limited information about this family of enzymes in either normal or diseased human liver. In this study, we have examined the synthesis of a 72 kDa type IV collagenase/gelatinase by human hepatic lipocytes in primary culture. Hepatic lipocytes were isolated from wedges of normal human donor liver by Pronase/collagenase perfusion, purified by density-gradient centrifugation, and established in primary culture on uncoated plastic. By Northern-blot analysis, the total RNA extracted from cultured human lipocytes was found to contain 3.4 kb mRNA for the 72 kDa type IV collagenase/gelatinase. Low levels of expression of this mRNA were observed in freshly isolated lipocytes but expression increased with the duration of lipocyte culture. Using anti-human 72 kDa type IV collagenase/gelatinase IgG, synthesized enzyme was immunolocalized to monensin treated human lipocyte cultures. De novo synthesis and secretion of 72 kDa type IV collagenase/gelatinase were confirmed by immunoprecipitation of radiolabelled enzyme from medium obtained from [35S]methionine-treated cells. Activity of the secreted enzyme was demonstrated by gelatin-zymography and by degradation of soluble, radiolabelled [14C]gelatin. The enzyme was released both in active and latent pro-enzyme forms and its inhibition profile was that of a metalloproteinase. These studies indicate that cultured human hepatic lipocytes express the gene for the 72 kDa type IV collagenase/gelatinase, and secrete this enzyme, particularly in prolonged primary culture. As this enzyme exhibits degradative activity against basement membrane collagen, its release by activated hepatic lipocytes in the space of Disse could lead to disruption of the normal subendothelial liver matrix. It is suggested that this enzyme may have an important role in human liver injury and fibrosis. PMID- 1445235 TI - Cytostasis induced in L1210 murine leukaemia cells by the S-adenosyl-L-methionine decarboxylase inhibitor 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine may be due to hypusine depletion. AB - The effects of inhibition of the capacity to form spermidine and spermine on cell growth were investigated using murine leukaemia L1210 cells and 5'-([(Z)-4-amino 2-butenyl]methylamino)-5'-deoxyadenosine (MDL 73811, AbeAdo), an enzyme-activated irreversible inhibitor of S-adenosyl-L-methionine decarboxylase. Putrescine levels were increased 80-fold, and spermidine and spermine levels were greatly reduced after a 3-day exposure to a maximally inhibitory dose of 10 microM AbeAdo. Addition of AbeAdo to the culture medium inhibited the growth of L1210 cells measured 3 days later in a dose-dependent manner, but, even at a dose of 10 microM, which was maximally effective, exposure to AbeAdo was not immediately cytostatic. However, the growth rate of L1210 cells chronically exposed to 10 microM-AbeAdo declined steadily until day 12, when the cells stopped growing. L1210 cells exposed to AbeAdo for 12 days could not be rescued from cytostasis by removal of the drug from the culture, but could be rescued by exposure to exogenous spermidine or spermine, indicating that the growth-inhibitory effects of AbeAdo were a result of spermidine and/or spermine depletion. It is suggested that elevated intracellular putrescine in AbeAdo-treated cells sustained limited growth in the absence of physiological levels of spermidine and spermine until certain critical and specific physiological role(s) fulfilled by spermidine (and/or spermine) became deficient resulting in cytostasis. N-(3-Aminopropyl)-1,4 diamino-cis-but-2-ene, a spermidine analogue that is a substrate for deoxyhypusine synthase, was able to mimic the effects of spermidine in reversing AbeAdo-induced cytostasis. Spermidine analogues such as 5,5-dimethylspermidine, which are not substrates for deoxyhypusine synthase, were not active in this way. These results provide evidence that the formation of hypusine in the protein synthesis initiation factor eIF-5A may be a critical role of spermidine essential for cell growth. PMID- 1445236 TI - Purification and characterization of a vitamin D3 25-hydroxylase from pig liver microsomes. AB - A cytochrome P-450 which catalyses 25-hydroxylation of vitamin D3 has been purified to apparent homogeneity from pig liver microsomes. The specific content of cytochrome P-450 was 12 nmol.mg of protein-1, and the preparation showed a single band with an apparent M(r) of 50,500 upon SDS/PAGE. A monoclonal antibody raised against the vitamin D3 25-hydroxylase reacted strongly with the purified 25-hydroxylating cytochrome P-450 from pig kidney microsomes [Bergman & Postlind (1990) Biochem. J. 270, 345-350]. The liver enzyme showed structural and functional properties very similar to those of the kidney enzyme. The two enzymes differed with respect to only one of the first 16 N-terminal amino acids. The vitamin D3 25-hydroxylase in pig liver microsomes exhibited a turnover and an apparent Km for 25-hydroxylation of vitamin D3 which were of the same order of magnitude as those of a well-characterized male-specific 25-hydroxylating cytochrome P-450 in rat liver microsomes. The two enzymes differed structurally. The pig liver enzyme was, in contrast to the rat liver enzyme, not sex-specific, and did not catalyse 16 alpha-hydroxylation of testosterone. These properties of the 25-hydroxylase in rat liver microsomes have led to questions on the role of microsomal 25-hydroxylation of vitamin D3. It is concluded that studies on microsomal 25-hydroxylation with the rat may be misleading. The results of the present study show that the pig appears to be a representative species for evaluation of vitamin D3 hydroxylases in other mammals, including man. PMID- 1445237 TI - Disruption of prosomes by some bivalent metal ions results in the loss of their multicatalytic proteinase activity and cancels the nuclease resistance of prosomal RNA. AB - Prosomes are ribonucleoprotein particles constituted by a variable set of about 20 proteins found associated with untranslated mRNA. In addition, they contain a small RNA, the presence of which has been an issue of controversy for a long time. The intact particles have a multicatalytic proteinase (MCP) activity and are very stable; we have never observed autodigestion of the particle by its intrinsic proteinase activity. Surprisingly it was found that Zn2+ and Cu2+ ions at concentrations of 0.1-1 mM disrupt the prosome particles isolated from HeLa cells and duck erythroblasts and abolish instantaneously its MCP activity, without altering the two-dimensional electrophoretic pattern of the constituent proteins. Fe2+, however, seems to induce autodegradation rather than dissociation of the prosome constituents. Most interestingly, protein or oligopeptide substrates protect the particle and its proteinase activity from disruption by Zn2+ or Cu2+. Nuclease-digestion assays reveal that the prosomal RNA, which is largely resistant in the intact particle, becomes digestible after dissociation of prosomes by Zn2+. These data give, for the first time, unambiguous proof of the presence of an RNA in the particle. Furthermore, they demonstrate a structure function relationship between the complex and its enzyme activity, which seems to be based on the particle as an entity and not on the single constituent proteins. PMID- 1445238 TI - Characterization of a calsequestrin-like protein from sea-urchin eggs. AB - Following our studies on the identification of a calsequestrin-like protein (CSLP) from sea-urchin eggs [Oberdorf, Lebeche, Head & Kaminer (1988) J. Biol Chem. 263, 6806-6809], we have characterized its Ca(2+)-binding properties and identified it as a glycoprotein. The molecule binds 23 mol of Ca2+/mol of protein, as determined by equilibrium dialysis. This is in the range reported for cardiac calsequestrin but is about half the binding capacity of striated muscle calsequestrin. The affinities of the CSLP for Ca2+ are decreased by increasing KCl concentrations (20-250 mM) and the presence of Mg2+ (3 mM) in the medium: the half-maximal binding values varied from 1.62 to 5.77 mM. Hill coefficients indicated mild co-operativity in the Ca2+ binding. Ca2+ (1-8 mM)-induced u.v. difference spectra and intrinsic fluorescence changes suggest a net exposure of aromatic residues to an aqueous environment. C.d. measurements showed minor Ca(2+)-induced changes in alpha-helical and beta-sheet content of less than 10%. These spectral changes are distinctly different from those found in muscle calsequestrin. Immunoblotting studies showed that the CSLP is distinct from calreticulin, a low-affinity Ca(2+)-binding protein. PMID- 1445239 TI - Extracellular fatty acids are not utilized directly for the synthesis of very-low density lipoprotein in primary cultures of rat hepatocytes. AB - In hepatocytes cultured in the presence of oleate (initial concn. 0.75 mM), the secretion of very-low-density lipoprotein (VLDL) triacylglycerol and, to a lesser extent, apoprotein B (apoB) increased with time, whereas there was a large decline in the extracellular concentration of fatty acid. There was thus no synchronous relationship between the extracellular fatty acid concentration and the secretion of VLDL. Rather, the appearance of VLDL in the medium was dependent on the intracellular triacylglycerol concentration. At a given concentration of extracellular fatty acid, cells depleted of triacylglycerol secreted less VLDL triacylglycerol and apoB than did control cells. A similar pattern was observed for triacylglycerol newly synthesized from extracellular [3H]oleate. By contrast, the synthesis and output of ketone bodies were directly dependent on the fatty acid concentration of the medium. These results suggest that, at least for oleic acid, extracellular fatty acids are not utilized directly for VLDL assembly, but first enter a temporary intracellular storage pool of triacylglycerol, which is the immediate precursor of secreted triacylglycerol. The size of this pool then determines the rate of secretion of VLDL triacylglycerol apoB. Ketogenesis, on the other hand, relies mainly on the direct utilization of extracellular fatty acids. PMID- 1445240 TI - Sequence of a novel cytochrome CYP2B cDNA coding for a protein which is expressed in a sebaceous gland, but not in the liver. AB - The major phenobarbital-inducible rat hepatic cytochromes P-450, CYP2B1 and CYP2B2, are the paradigmatic members of a cytochrome P-450 gene subfamily that contains at least seven additional members. Specific oligonucleotide probes for these genomic members of the CYP2B subfamily were used to assess their tissue specific expression. In Northern-blot analysis a probe specific to gene 4 (which is designated now as CYP2B12) hybridized to a single mRNA present in the preputial gland, an organ which is used as a model for sebaceous glands, but did not hybridize to mRNA isolated from the liver or from five other tissues of untreated or Aroclor 1254-treated rats. The cDNA sequence for the CYP2B12 RNA was determined from overlapping cDNA clones and contained a long open reading frame of 1476 bp. The nucleotide sequence of the CYP2B12 cDNA was 85% similar to the sequence of the CYP2B1 cDNA in its coding region and was different from any CYP2B cDNA characterized until now. The cDNA-derived primary structure of the CYP2B12 protein contains a signal sequence for its insertion into the endoplasmic reticulum and the putative haem-binding site characteristic of cytochromes P-450. A part of the potential haem pocket of CYP2B12 was identical with a similar structure in a bacterial protocatechuate dioxygenase. In immunoblot analysis of preputial-gland microsomes, antibodies against CYP2B1 recognized a single abundant protein with a lower apparent molecular mass than that of CYP2B1. Our results demonstrate that the CYP2B12 protein has the potential to be enzymically active and are the first demonstration that a member of the CYP2B subfamily is expressed exclusively and at high levels in an extrahepatic organ. PMID- 1445241 TI - Crystal structure of papain-E64-c complex. Binding diversity of E64-c to papain S2 and S3 subsites. AB - In order to investigate the binding mode of E64-c (a synthetic cysteine proteinase inhibitor) to papain at the atomic level, the crystal structure of the complex was analysed by X-ray diffraction at 1.9 A (1 A is expressed in SI units as 0.1 nm) resolution. The crystal has a space group P2(1)2(1)2(1) with a = 43.37, b = 102.34 and c = 49.95 A. A total of 21,135 observed reflections were collected from the same crystal, and 14811 unique reflections of up to 1.9 A resolution [Fo > 3 sigma(Fo)] were used for the structure solution and refinement. The papain structure was determined by means of the molecular replacement method, and then the inhibitor was observed on a (2 magnitude of Fo magnitude of Fc) difference Fourier map. The complex structure was finally refined to R = 19.4% including 207 solvent molecules. Although this complex crystal (Form II) was polymorphous as compared with the previously analysed one (Form I), the binding modes of leucine and isoamylamide moieties of E64-c were significantly different from each other. By the calculation of accessible surface area for each complex atom, these two different binding modes were both shown to be tight enough to prevent the access of solvent molecules to the papain active site. With respect to the E64-c-papain binding mode, molecular-dynamics simulations proposed two kinds of stationary states which were derived from the crystal structures of Forms I and II. One of these, which corresponds to the binding mode simulated from Form I, was essentially the same as that observed in the crystal structure, and the other was somewhat different from the crystal structure of Form II, especially with respect to the binding of the isoamylamide moiety with the papain S subsites. The substrate specificity for the papain active site is discussed on the basis of the present results. PMID- 1445242 TI - The stereochemical course of sulphuryl transfer catalysed by arylsulphatase II from Aspergillus oryzae. AB - Phenyl [(R)-16O,17O,18O]sulphate was synthesized and used to study the stereochemical course of sulphuryl transfer to p-cresol catalysed by arylsulphatase II from Aspergillus oryzae. The reaction was shown to proceed with retention of configuration at the sulphur atom, providing evidence for the involvement of a sulpho-enzyme intermediate on the reaction pathway. PMID- 1445243 TI - Real-time study of the urea cycle using 15N n.m.r. in the isolated perfused rat liver. AB - 1. Isolated rat liver was perfused with 10 mM-15NH4Cl, 5 mM-lactate and 1 mM ornithine, or with 3 mM-[15N]alanine and 1 mM-ornithine, in haemoglobin-free medium. The liver was physiologically stable for over 3 h and synthesized urea at the rate of 1.15 mumol.min-1.g of liver-1 (15NH4(+)-perfused) or 0.41 mumol.min 1.g-1 ([15N]alanine-perfused). 2. The perfused liver was continuously monitored by 15N n.m.r. spectroscopy at 20.27 MHz for 15N. Well-resolved 15N resonances of precursors and intermediates of the urea cycle, present at tissue concentrations of 0.2-3.0 mumol/g, were observed from the intact liver in 5-40 min of acquisition. Key metabolites in liver extract and the final perfusion medium were analysed by n.m.r. and by biochemical assays to determine fractional 15N enrichment and the total 15N recovery. 3. In 15NH4(+)-perfused liver (n = 6), 15N incorporation into glutamate and alanine (1.0-1.3 mumol/g), as well as progressive formation of [15N2]urea, was observed during the first 2 h of perfusion. In the second and third hour, hepatic concentrations of [omega 15N]citrulline and [omega,omega'-15N]argininosuccinate increased to n.m.r. detectable levels (0.3-0.9 mumol/g). The [15N]aspartate pool was large in the absence of added ornithine, but on its addition was rapidly incorporated into argininosuccinate (n = 3). 4. In [15N]alanine-perfused liver, major metabolites were [15N]glutamate, [gamma-15N]glutamine and [15N]urea. Urea-cycle intermediates were undetectable. 5. The results suggest that, in intact liver provided with excess ammonia, low concentrations of cytosolic argininosuccinate synthetase and argininosuccinate lyase limited the rate of metabolite flux in the urea cycle. By contrast, in alanine-perfused liver at a physiological rate of urea synthesis, mitochondrial carbamoylphosphate synthetase was rate-limiting. 6. The potential utility of 15N n.m.r. for study of metabolite channelling through urea-cycle enzymes in intact liver is discussed. PMID- 1445244 TI - Zn(2+)-heparin interaction studied by potentiometric titration. AB - Measurement of the decrease in pH that accompanies the addition of Zn2+ to heparin in solution provided an indirect method of examining cation-polyanion interaction. Construction of plots analogous to isothermal saturation binding plots revealed the existence, for defined conditions of interaction, of a [heparin]-independent direct proportionality between the fraction of the maximal pH change occurring and the [Zn2+]/[heparin disaccharide] ratio. This accords with results from polarimetric examination of Ca(2+)- and Cu(2+)-heparin interactions. It suggests that, under the conditions used, cation-heparin interaction may result in the formation of a complex that exists in a colloid like phase, between which and the aqueous phase, exchange of cations does not follow simple solution-phase reversible equilibrium thermodynamic behaviour. The results suggest that the putative Zn(2+)-containing complex is less stable in the presence of NaCl than is the corresponding Ca(2+)-containing complex. Addition of Zn2+ to low concentrations of heparins is accompanied by the usual decrease in pH, followed by a removal of H+ from solution as the [Zn2+]/[heparin disaccharide] ratio increases, suggesting dissolution of the putative complex. This reversal of the initial pH change was not seen for most other cation-heparin interactions under the conditions studied. PMID- 1445246 TI - Characterization and purification of a novel dATP-binding protein in eukaryotes. AB - We characterized and purified an acidic dATP-binding protein, which, in its active form, resides in the nuclear fraction of a range of cells from mammals (including pig liver) and baker's yeast (Saccharomyces cerevisiae). This protein exhibits a high degree of specificity for the deoxy form of the naturally occurring nucleoside triphosphates and shows a marked preference for the purine deoxynucleoside triphosphates dATP and dGTP. The protein cleaves the terminal phosphate of dATP and appears to retain the dADP moiety of the nucleotide in a reaction that is resistant to both SDS and 8 M-urea. Fractionation of the nuclear preparation followed by non-denaturing PAGE and SDS/PAGE electrophoresis was sufficient to produce pure protein. The occurrence of this activity in all nuclei tested suggests that it plays an important role in nuclear metabolism. The specificity of the enzyme for deoxynucleoside triphosphates further suggests a role for this enzyme in DNA replication or repair, but the acidity of the protein argues against a direct interaction with DNA, and, indeed, the catalytic activity is not modulated by the inclusion of DNA in a variety of physical forms. PMID- 1445245 TI - Purification and characterization of an acetone-inducible cytochrome P-450 from hamster liver microsomes. AB - A form of cytochrome P-450 has been purified to electrophoretic homogeneity from the hepatic microsomes of Syrian golden hamsters treated with acetone. This P-450 form, designated ha P-450j, had an M(r) of approximately 55,000, bound dimethyl sulphoxide and exhibited a CO-reduced absorbance maximum at 451 nm. The absolute spectra of its oxidized form indicated that ha P-450j was predominantly in the low-spin state. In a reconstituted system, ha P-450j showed relatively low catalytic activities towards 7-ethoxycoumarin, 7-ethoxyresorufin, aminopyrine, ethylmorphine and benzphetamine, whereas it catalysed the oxidation of aniline, acetone and thiobenzamide with a high catalytic-centre activity. In addition, ha P-450j catalysed at a high rate the high-affinity component of dimethylnitrosamine N-demethylase; in contrast, only the low-affinity component of diethylnitrosamine N-de-ethylase was efficiently catalysed. The addition of cytochrome b5 to the reconstitution system decreased the Km value for dimethylnitrosamine N-demethylase by a factor of 5 and increased the Vmax. value, and slightly enhanced the other activities. Thiobenzamide and diethyldithiocarbamate were found to be the most effective inhibitors of the ha-P 450j-dependent aniline hydroxylation. Polyclonal antibodies against rat P-450j recognized ha P-450j in immunoblots of control and treated hamster liver microsomes. Treatment of hamsters with acetone increased the apparent abundance of ha P-450j in microsomes, whereas phenobarbital and beta-naphthoflavone did not induce it. Analysis of N-terminal amino acid sequences demonstrated that ha P 450j has a high degree of sequence identity with rat P-450j. All the evidence presented in this study indicates that ha P-450j could represent the hamster orthologue of the previously described CYP2E1(s) of other species. PMID- 1445247 TI - Evaluation of hydrogen-bonding and enantiomeric P2-S2 hydrophobic contacts in dynamic aspects of molecular recognition by papain. AB - 1. 2-(N'-Acetyl-D-phenylalanyl)hydroxyethyl 2'-pyridyl disulphide (compound IV) (m.p. 59 degrees C; [alpha]D20 -6.6 degrees (c 1.2 in methanol)) was synthesized. 2. The results of a study of the pH-dependence of the second-order rate constant (k) for its reaction with the catalytic-site thiol group (Cys-25) of papain (EC 3.4.22.2) together with analogous kinetic data for the reactions of related time dependent inhibitors, notably the L-enantiomer of compound (IV) (compound III) and the L- and D-enantiomers of 2-(N'-acetylphenylalanylamino)ethyl 2'-pyridyl disulphide (compounds I and II respectively), were used to assess the contributions of the (P1)-NH ... O = C < (Asp-158) and (P2) > C = O ... H-N-(Gly 66) hydrogen bonds and enantiomeric P2-S2 hydrophobic contacts in two manifestations of dynamic molecular recognition in papain-ligand association: (a) signalling to the catalytic-site region to provide for a (His-159)-IM(+)-H assisted transition state and (b) the dependence of P2-S2 stereoselectivity on hydrogen-bonding interactions outside the S2 subsite. The analysis involved determination of the reactivities of individual ionization states of the reactions (pH-independent rate constants, k) and associated macroscopic pKa values and difference kinetic specificity energies (delta delta GKS = RT1n(k1/k2), where k1 is the pH-independent second-order rate constant for reaction with one inhibitor and k2 is the analogous rate constant in the same ionization state for reaction with another inhibitor so that, when the structural change provides that k2 > k1, delta delta GKS is positive. 3. The kinetic data further illuminate the nature of the interdependence of binding interactions in papain first noted by Kowlessur, Topham, Thomas, O'Driscoll, Templeton & Brocklehurst [(1989) Biochem. J. 258, 755-764] in the S2 subsite, S1-S2 intersubsite and catalytic-site regions. Of particular note is the apparent dependence of the binding of the N-Ac-D-Phe moiety on the binding of the leaving group to (His-159)-Im+H and the fact that the resulting rate enhancement is more effective when (P1)-N-H is absent than when it is present. This result revealed by kinetic analysis goes beyond the conclusion suggested by model building that it is possible to make all of the binding contacts in complexes involving the D enantiomers [(II) and (IV)] as in those involving the L-enantiomers [(I) and (III)].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1445248 TI - Taurolithocholate-induced Ca2+ release is inhibited by phorbol esters in isolated hepatocytes. AB - The monohydroxy bile acid taurolithocholate (TLC) causes a rapid and transient increase in free cytosolic Ca2+ concentration ([Ca2+]i) in suspensions of rat hepatocytes similar to that elicited by the InsP3-dependent hormone vasopressin. The effect of the bile acid is due to a mobilization of Ca2+, independent of InsP3, from the endoplasmic reticulum (ER). Short-term preincubation of cells with the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), which activates protein kinase C (PKC), blocked the increase in [Ca2+]i induced by TLC, but did not alter that mediated by vasopressin. We obtained the following results, indicating that the effect of PMA is mediated by the activation of PKC. (1) Phorbol esters were effective over a concentration range where they activate PKC (IC50 = 0.5 nM); (2) phorbol esters that do not activate PKC did not inhibit the effects of TLC; (3) the permeant analogue oleoylacetylglycerol mimicked the inhibitory effect of PMA; (4) lastly, the inhibition of the TLC-induced Ca2+ mobilization by phorbol esters was partially prevented by preincubating the cells with the PKC inhibitors H7 and AMG-C16. Preincubating hepatocytes with PMA had no effect on the cell uptake of labelled TLC, indicating that the phorbol ester does not interfere with the transport system responsible for the accumulation of bile acids. In saponin-treated liver cells, PMA added before or after permeabilization failed to abolish TLC-induced Ca2+ release from the ER. The possibility is discussed that PMA, via PKC activation, may alter the intracellular binding or the transfer of bile acids in the liver. PMID- 1445249 TI - Characterization of the binding of plasminogen activators to plasma membranes from human liver. AB - The binding of tissue-type plasminogen activator (t-PA) to membranes prepared from human liver was investigated, and a specific, saturable, high-affinity binding site (Kd = 3.4 nM) was identified. The binding of t-PA to liver membranes was not affected by an excess of D-mannose or D-galactose, or by active urokinase (u-PA), whereas binding of t-PA to membranes prepared from human HepG2 hepatoma cells was inhibited by u-PA. HepG2-membrane-bound t-PA was fully complexed to PA inhibitor 1 (PAI-1), whereas liver-membrane-bound t-PA was not complexed. Gel filtration on Sephacryl S300 of membrane proteins solubilized in deoxycholate revealed that high-affinity t-PA binding activity elutes at an apparent molecular mass of 40 kDa. Monoclonal antibodies specific for the growth factor and the kringle 2 domains inhibited the binding of t-PA to liver membranes and the catabolism of t-PA by rat hepatoma cells. Human liver membranes also bound u-PA; binding was inhibited by pro-u-PA, the N-terminal fragment of u-PA, but not by the 33 kDa form of u-PA or by t-PA. Our results show that human liver membranes contain a specific 40 kDa binding protein for t-PA that is different from the PAI 1-dependent receptor described on HepG2 cells and the mannose receptor isolated from human liver. PMID- 1445250 TI - Mitogen-induced tyrosine phosphorylation of 41 kDa and 43 kDa proteins. Potential role in integrating multiple mitogenic signalling pathways. AB - We have examined the possible involvement of pertussis toxin (PT)-sensitive GTP binding protein and protein kinase C (PKC) in mitogen-induced tyrosine phosphorylation of the 41 kDa and 43 kDa cytosol proteins using PT-pretreated (inactivation of PT-sensitive GTP-binding protein) or phorbol 12-myristate 13 acetate (PMA)-pretreated (depletion of PKC) mouse fibroblasts. The effects of the inactivation of PT-sensitive GTP-binding protein and the depletion of PKC on mitogen-stimulated tyrosine phosphorylation of the proteins were similar and varied significantly and systematically in response to growth factors. The important finding was that such inhibitory effects of PT-sensitive GTP-binding protein inactivation and PKC depletion on protein tyrosine phosphorylation induced by each mitogen always correlated well with their inhibitory effects on each mitogen-stimulated DNA synthesis. Although the extent of platelet-derived growth-factor-induced phosphorylation of the proteins was decreased to approx. 50% in PT- and PMA-pretreated cells compared with native cells, protein phosphorylation itself was not affected and occurred at identical sites on each protein in native, PT- and PMA-pretreated cells. These results suggest that: (1) 41 kDa and 43 kDa proteins are located downstream of PT-sensitive GTP-binding protein and PKC in the mitogenic signalling pathways of growth factors, (2) protein phosphorylation occurs via a cascade of events which includes the activation of the receptor tyrosine kinases, PKC and other unidentified kinase(s) which directly participate(s) in the phosphorylation of the 41 kDa and 43 kDa proteins, and (3) their phosphorylation may play an important role in integrating multiple mitogenic signalling pathways. PMID- 1445251 TI - Kinetics of activation of the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein. AB - The activation of transcription initiation from the P4 promoter of pBR322 by the Escherichia coli cyclic AMP receptor protein (CRP) has been investigated using a fluorescence abortive initiation assay. The effect of the cyclic-AMP/CRP complex on the linear P4 promoter was to increase the initial binding (KB) of RNA polymerase to the promoter by about a factor of 10, but the rate of isomerization of closed to open complex (kf) was unaffected. One molecule of CRP per promoter was required for activation, and the concentration of cyclic AMP producing half maximal stimulation was about 7-8 microM. Supercoiling caused a 2-3-fold increase in the rate of isomerization of the CRP-activated promoter, but weakened the initial binding of polymerase by about one order of magnitude. The unactivated supercoiled promoter was too weak to allow reliable assessment of kinetic parameters against the high background rate originating from the rest of the plasmid. PMID- 1445252 TI - Site-directed mutagenesis of the leech-derived factor Xa inhibitor antistasin. Probing of the reactive site. AB - Antistasin (ATS) is a leech-derived 119-amino-acid protein which exhibits potent and highly selective inhibition of coagulation Factor Xa. It inhibits Factor Xa according to a common mechanism of serine-proteinase inhibitors in which a conformationally rigid substrate-like reactive site is presented to the enzyme. In this study a recombinant version of ATS was expressed and purified utilizing a yeast expression system in order to probe the reactive site P1 (Arg-34) and P1' (Val-35) residues by site-directed mutagenesis. The results demonstrate the requirement for a positively charged residue in the P1 position of ATS, with an arginine residue preferred over a lysine, yielding K1 values of 61 pM and 1.28 nM respectively. Mutation of the P1 arginine residue to the non-polar amino acid leucine abolished its inhibitory potency toward Factor Xa. The role of the C terminal domain of ATS, which shares significant amino acid sequence identity with the N-terminal domain, was investigated by creating a second reactive site in the corresponding position of the C-terminal domain. The inhibitory activity of this mutant demonstrated that the C-terminal domain of ATS is not folded into the proper conformation necessary to create a functional inhibitory domain. PMID- 1445253 TI - An evolutionary perspective on glutathione transferases inferred from class-theta glutathione transferase cDNA sequences. AB - We report the cDNA sequence for rat glutathione transferase (GST) subunit 5, which is one of at least three class Theta subunits in this species. This sequence, when compared with that of subunit 12 recently published by Ogura, Nishiyama, Okada, Kajita, Narihata, Watabe, Hiratsuka & Watabe [(1991) Biochem. Biophys. Res. Commun. 181, 1294-1300] proves that Theta is a separate multigene class of GST with little amino acid sequence identity with Mu-, Alpha- or Pi class enzymes. The amino acid sequence identity of class-Theta subunits is highly conserved in rat, the fruitfly Drosophila, maize (Zea mays) and Methylobacterium, which suggests that this family is representative of the ancient progenitor GST gene and originates from the endosymbioses of a purple bacterium leading to the mitochondrion. The high conservation of class Theta brings into prominence that Alpha-, Mu- and Pi-class enzymes, which are not present in plants, derive from a Theta-class gene duplication before the divergence of fungi and animals and, given the binding properties of the Alpha-, Mu- and Pi-classes, suggests a role for these in the evolution of fungi and animals. PMID- 1445254 TI - Purification and properties of DNA polymerase from Bacillus caldotenax. AB - A thermostable DNA polymerase was prepared from Bacillus caldotenax by using a four-step chromatography procedure. The protein exists as a monomer of M(r) 94,000, has a pI of 4.9 and has no associated 3'-5' or 5'-3'-exonuclease activities or endonuclease activity. The temperature optimum of the enzyme was about 70 degrees C and the pH for maximum activity was about 7.5. The enzyme has an absolute requirement for a bivalent cation, and maximum activity was obtained at the unusually high concentration of 70 mM-MgCl2. Mg2+ could be replaced by MnCl2 or CoCl2, with decreased activity, at the lower optimal concentrations of 1 mM and 2.5 mM respectively. Enzyme activity was inhibited in the presence of 2',3'-dideoxy-TTP, arabinosyl-CTP and aphidicolin. Enzyme activity was stimulated with KCl concentrations of about 100 mM, and concentrations of univalent salts above about 150 mM inhibited activity. The enzyme could use activated calf thymus DNA, poly(dA).p(dT)10 or primed single-stranded phage M13 DNA as a template and maximum activity was obtained with poly(dA).p(dT)10. The enzyme was inactive on unprimed single-stranded DNA, double-stranded DNA and polyribonucleotide template/primer. The apparent Km values for individual dNTPs, determined with the other dNTPs at saturating concentrations, were 5.7 microM (dCTP), 6.3 microM (dATP, dGTP) and 6.4 microM (dTTP). The Km value for the overall incorporation of each dNTP from an equimolar mixture of all four dNTPs was 24.7 microM. The kcat. value was about 1.05 s-1. The kcat./Km value was 0.16-0.18 M-1.s-1 for individual dNTPs and 0.04 for the incorporation of an equimolar mixture of all four dNTPs. Some of the properties of the enzyme show it may be classified as an alpha-Type DNA polymerase. PMID- 1445255 TI - The Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent high affinity phorbol ester receptor. AB - The Caenorhabditis elegans unc-13 mutant is a member of a class of mutants that have un-coordinated movement. Mutations of the unc-13 gene cause diverse defects in C. elegans, including abnormal neuronal connections and modified synaptic transmission in the nervous system. unc-13 cDNA encodes a protein (UNC-13) of 1734 amino acid residues with a predicted molecular mass of 198 kDa and sequence identity to the C1/C2 regions but not to the catalytic domain of the ubiquitously expressed protein kinase C family [Maruyama & Brenner (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 5729-5733]. To characterize the phorbol ester binding site of the UNC-13 protein, cDNA encoding the C1/C2-like regions (amino acid residues 546 940) was expressed in Escherichia coli and the 43 kDa recombinant protein was purified. Phorbol ester binding to the 43 kDa protein was zinc- and phospholipid dependent, stereospecific and of high affinity (Kd 67 nM). UNC-13 specific antisera detected a protein of approx. 190 kDa in wild-type (N2) but not in mutant (e1019) C. elegans cell extracts. We conclude that UNC-13 represents a novel class of phorbol ester receptor. PMID- 1445256 TI - Molecular-dynamics investigation of molecular flexibility in ligand binding. AB - The molecular flexibility of an inhibitor in ligand-binding process has been investigated by the mass-weighted molecular-dynamics simulation, a computational method adopted from the standard molecular-dynamics simulation and one by which the conformational space of a biomolecular system over potential energy barriers can be sampled effectively. The bimolecular complex of the aspartyl proteinase from Rhizopus chinensis, rhizopuspepsin, and an octapeptide inhibitor was previously studied in a mass-weighted molecular-dynamics simulation; the study has been extended for investigating the molecular flexibility in ligand binding. A series of mass-weighted molecular-dynamics simulations was carried out in which libration of the inhibitor dihedral angles was parametrically controlled, and threshold values of dihedral angle libration amplitudes were observed from monitoring the sampling of the enzyme binding pocket by the inhibitor in the simulations. The computational results are consistent with the general notion of molecular-flexibility requirement for ligand binding; the freedom of dihedral rotations of side-chain groups was found to be particularly important for ligand binding. Thus the critical degree of molecular flexibility which would contribute to effective enzyme inhibition can be obtained precisely from the modified molecular-dynamics simulations; the procedure described herein represents a first step toward providing quantitative measures of such a molecular-flexibility index for inhibitor molecules that have been otherwise targeted for optimal protein ligand interactions. PMID- 1445257 TI - Protein kinase C phosphorylation of cardiac troponin T decreases Ca(2+)-dependent actomyosin MgATPase activity and troponin T binding to tropomyosin-F-actin complex. AB - Effects of phosphorylation of bovine cardiac troponin T (TnT) by protein kinase C on the Ca(2+)-stimulated MgATPase activity of reconstituted actomyosin complex and the binding of TnT to tropomyosin(Tm)-F-actin were investigated. The Ca(2+) stimulated MgATPase of actomyosin containing phosphorylated TnT (1.8 mol of P/mol), compared with that containing unphosphorylated TnT, was decreased by up to 48%. Phosphorylation of TnT also decreased (up to 48%) its maximum binding to Tm-F-actin, which was accompanied by a decrease (up to 3.5-fold) in its apparent binding affinity. The findings indicate that the effects of phosphorylated TnT in decreasing actomyosin MgATPase might be secondary to its decreased interactions with the other components of the thin filament, representing a new mechanism underlying the negative inotropic responses of various cardiac preparations to protein kinase C-activating phorbol esters. PMID- 1445258 TI - Characterization of three osteogenesis imperfecta collagen alpha 1(I) glycine to serine mutations demonstrating a position-dependent gradient of phenotypic severity. AB - Type I collagen alpha 1(I) glycine to serine substitutions, resulting from G-to-A mutations, were defined in three cases of osteogenesis imperfecta (OI). The Gly substitutions displayed a gradient of phenotypic severity according to the location of the mutation in the collagen triple helix. The most C-terminal of these, Gly565 to Ser, led to the lethal perinatal (type II) form of OI, whereas the more N-terminal mutations, Gly415 and Gly352 to Ser, led to severe OI (type III/IV) and moderate OI (type IVB) respectively. These data support the notion that glycine substitutions towards the C-terminus of the alpha 1(I) or alpha 2(I) chains will be more clinically severe than those towards the N-terminus. This results from the more disruptive effect of the mutations at the C-terminus on helix initiation and C- and N-terminal helix directional propagation. This generalization must be modified by considering the nature of the glycine substitution and the surrounding amino acid sequence, since the helix is composed of subdomains of differing stability which will affect the ability of helix re nucleation and propagation. PMID- 1445259 TI - Evidence for dissociation of gluconeogenesis stimulated by non-esterified fatty acids and changes in fructose 2,6-bisphosphate in cultured rat hepatocytes. AB - In order to examine the role of fructose 2,6-bisphosphate (Fru-2,6-P2) in non esterified-fatty-acid-stimulated gluconeogenesis, Fru-2,6-P2 levels were measured in cultured rat hepatocytes under conditions mimicking the fasted state. After addition of either 1.5 mM-palmitate or 10 nM-glucagon, [U-14C]lactate incorporation into glucose increased 2-fold, but only glucagon suppressed Fru-2,6 P2. Prevention of palmitate oxidation with a carnitine palmitoyltransferase-I inhibitor (2-bromopalmitate) diminished glucose production and Fru-2,6-P2 levels. Addition of exogenous glucose to the media increased Fru-2,6-P2 in a dose-related manner, which was further augmented by addition of palmitate. When Fru-2,6-P2 levels were examined in cells cultured under conditions mimicking the fed state (significantly higher basal Fru-2,6-P2 levels and lower glucose production), palmitate oxidation was associated with a significant fall in Fru-2,6-P2. In conclusion, the present studies have demonstrated a dissociation between fatty acid-stimulated gluconeogenesis and changes in Fru-2,6-P2 in cultured rat hepatocytes. Further experiments suggest that the accumulation of intracellular hexose 6-phosphate as a result of fatty-acid-stimulated gluconeogenesis masks a putative inhibitory effect of fatty acids on Fru-2,6-P2 concentrations. PMID- 1445260 TI - Substrate specificity and distribution of UDP-GalNAc:sialylparagloboside N acetylgalactosaminyltransferase in the human stomach. AB - The detailed substrate specificity of the UDP-GalNAc:sialylparagloboside N acetylgalactosaminyltransferase to form the Sd(a+) blood group active carbohydrate determinant GalNAc beta 1-4(NeuAc alpha 2-3)Gal was studied using a membrane fraction prepared from human gastric fundic mucosa. Various sialosylated oligosaccharides and gangliosides were examined as acceptor substrates. Oligosaccharide substrates were fluorescence-labelled with 2-aminopyridine, and the transferase activity was quantified by h.p.l.c. using a reversed-phase column. The structures of the products were determined by glycosidase degradation and proton n.m.r. 3'-Sialyl-lactose (II3NeuAcLac), 3'-sialyl-lactotetraose (IV3NeuAcLc4), and 3'-sialyl-lactoneotetraose (IV3NeuAcnLc4) were good substrates for the beta 1-4GalNAc transferase in gastric fundic mucosa, but 6'-sialyl lactoneotetraose (IV6NeuAcnLc4) or 6'-sialyl-lactose (II6NeuAcLac) were not. Gangliosides with a terminal NeuAc alpha 2-3Gal residue such as GM3, sialylparagloboside, GM1b and GD1a were also studied. The activity of beta 1 4GalNAc transfer to sialylparagloboside was much higher than that to GM2, GM1b or GD1a in spite of them having the same terminal residue. Measurement of the activity of the beta 1-4GalNAc transferase in biopsy specimens demonstrated that the activity was localized in gastric fundic mucosa and was absent in pyloric mucosa, intestinal metaplasia and gastric cancer tissue. Thus the beta 1-4GalNAc transferase present specifically in fundic mucosa required a NeuAc alpha 2-3Gal residue connected to either type-1-chain or type-2-chain oligosaccharides. In glycolipids, the acceptor specificity was restricted to NeuAc alpha 2-3Gal beta 1 4GlcNAc because the NeuAc alpha 2-3Gal beta 1-3GalNAc structure in ganglio-series glycolipids was not a good acceptor substrate. PMID- 1445261 TI - The binding of amide substrate analogues to phospholipase A2. Studies by 13C nuclear-magnetic-resonance and infrared spectroscopy. AB - (R)-(2-dodecanamidoisohexyl)phosphocholine (DAHPC), labelled with 13C at the amide carbonyl group, has been synthesized and its binding to bovine pancreatic phospholipase A2 (PLA2) studied by n.m.r. and i.r. spectroscopy. Two-dimensional 1H-n.m.r. spectra show that, in the presence of Ca2+, DAHPC binds to the active site of the enzyme in a similar manner to other phospholipid amide substrate analogues. The environment of the labelled carbonyl group has been investigated by a combination of 13C n.m.r. and difference-Fourier-transform i.r. spectroscopy. The carbonyl resonance shifts 3 p.p.m. downfield on the binding of DAHPC to PLA2. The carbonyl absorption frequency decreases by 14-18 cm-1, accompanied by a marked sharpening of the absorption band. These results indicate that the carbonyl bond undergoes significant polarization in the enzyme-ligand complex, facilitated by the enzyme-bound Ca2+ ion. This suggests that ground state strain is likely to promote catalysis in the case of substrate binding. Simple calculations, based on the i.r. data, indicate that the carbonyl bond is weakened by 5-9 kJ.mol-1. This is the first report of observation of the amide vibration of a bound ligand against the strong background of protein amide vibrations. PMID- 1445262 TI - Guanine nucleotide is essential and Ca2+ is a modulator in the exocytotic reaction of permeabilized rat mast cells. AB - Exocytosis from metabolically depleted permeabilized rat mast cells was measured in response to provision of Ca2+ and guanine nucleotide [GTP or guanosine 5' [gamma-thio]triphosphate (GTP[S])]. For cells permeabilized in simple salt solutions (NaCl), both of these effectors were required to induce secretion. Exclusion of Mg2+ caused an increase in both the sensitivity of the system to GTP and the extent of secretion elicited, while having no such effects on secretion induced by GTP[S]. The effect of Mg2+ depletion on the ability of GTP to stimulate secretion is probably due to the dependence on Mg2+ of the GTPase activity of GE (a postulated GTP-binding protein which mediates exocytosis). This argues that a persistent stimulus to the G-protein is required to support secretion. Affinity for both GTP[S] and GTP is enhanced when the cells are permeabilized in zwitterionic electrolytes (glutamate, gamma-aminobutyric acid, glycine) instead of NaCl. Under these conditions, secretion occurs in response to provision of either GTP[S] [in the effective absence of Ca2+ (pCa 9)] or Ca2+ (in the absence of guanine nucleotide). Secretion induced by GTP[S] is strongly promoted by the presence of Mg2+ at concentrations in the millimolar range; this promotion by Mg2+ declines as the concentration of Ca2+ is elevated towards pCa 7. At pCa 6, Mg2+ is without effect. Ca(2+)-induced secretion requires the provision of MgATP. Since this is further enhanced by low concentrations (< 100 microM) and then inhibited by high concentrations of GDP, the essential role of ATP is likely to be in the maintenance of GTP via transphosphorylation by a nucleoside diphosphate kinase reaction. Thus, under conditions of high affinity (glutamate environment), GTP[S] alone is capable of inducing exocytosis. Ca2+ acts in concert with guanine nucleotides: it enhances the rate and extent of secretion and increases the affinity for Mg2+ and guanine nucleotides in the activation of the GTP-binding protein (GE) which regulates exocytosis. PMID- 1445263 TI - Characterization of GLUT3 protein expressed in Chinese hamster ovary cells. AB - We have expressed GLUT3 protein, an isoform of a facilitative glucose transporter, in Chinese hamster ovary cells by transfection of its cDNA using an expression vector. The expressed GLUT3 protein was detected by Western-blot analysis as a broad band of 45-65 kDa, indicating intensive glycosylation of the protein. The expressed GLUT3 protein was observed, by immunofluorescence staining, to be located mainly at the plasma membrane, and its expression was associated with a marked increase in glucose-transport activity. Kinetic analysis revealed that the Km value of GLUT3 protein for 3-O-methylglucose uptake was approx. 35% of that of GLUT1 protein, whereas the Km value of GLUT3 protein for 2 deoxy-D-glucose uptake was very similar to that of GLUT1 protein. The Vmax. value of GLUT3 protein for 3-O-methylglucose and 2-deoxyglucose uptake was approx. 20 50% of that of GLUT1 protein. GLUT3 protein was well photolabelled with [3H]cytochalasin B or a mannose derivative, 2-N-4-[3H](1-azi-2,2,2 trifluoroethyl)benzoyl-1,3-bis-(D-mannos -4-yloxy)-2- propylamine. Thus GLUT3 protein has very similar characteristics to GLUT1 protein including its subcellular localization, but exhibits lower Km and Vmax. values for 3-O methylglucose uptake. PMID- 1445264 TI - Trehalase from male accessory gland of an insect, Tenebrio molitor. cDNA sequencing and developmental profile of the gene expression. AB - A cDNA of alpha alpha-trehalase (EC 3.2.1.28) from a cDNA library of male bean shaped accessory gland of the mealworm beetle, Tenebrio molitor, has been isolated by the homology screening approach. Sequence analysis of the cDNA (1830 bp) revealed that the cDNA encoded a protein of 555 amino acids with a calculated M(r) of 64457. The deduced amino acid sequence had significant similarities to rabbit small intestine and Escherichia coli trehalases. Northern blotting and semi-quantitative PCR analyses revealed that a trehalase transcript with about 2.0 kb was abundant in bean-shaped accessory glands. In the glands, the amount of trehalase transcript increased from 1 to 2 days after adult ecdysis. These tissue and stage-specific gene expressions of trehalase corresponded to the tissue- and stage-specificity of trehalase activity. PMID- 1445265 TI - Involvement of intracellular Ca2+ and K+ in dissipation of the mitochondrial membrane potential and cell death induced by extracellular ATP in hepatocytes. AB - Isolated rat hepatocytes were incubated with extracellular ATP to induce a prolonged increase in intracellular Ca2+ ([Ca2+]i) and a loss of viability within 2 h. By using video-intensified fluorescence microscopy, the effects of exposure to extracellular ATP on [Ca2+]i, mitochondrial membrane potential (MMP) and cell viability were determined simultaneously in individual living hepatocytes. The increase in [Ca2+]i on exposure to ATP was followed by a decreasing MMP; there were big differences between individual cells. Complete loss of the MMP occurred before cell death was observed. Omission of K+ from the incubation medium decreased the cytotoxicity of ATP; under these conditions, intracellular K+ was decreased by more than 80%. Treatment with nigericin also depleted intracellular K+ and decreased ATP-induced toxicity. Protection against loss of viability by means of a decrease in intracellular [K+] was reflected by maintenance of the MMP. These observations suggest that ATP-induced cell death may be caused by a mechanism that has been described for isolated mitochondria: after an increase in Ca2+ levels, a K+ influx into mitochondria is induced, which finally disrupts the MMP and leads to cell death. PMID- 1445266 TI - Structural differences between heparan sulphates of proteoglycan involved in the formation of basement membranes in vivo by Lewis-lung-carcinoma-derived cloned cells with different metastatic potentials. AB - This study addresses the characterization of heparan sulphates of the basement membrane proteoglycans in tumour formed after the subcutaneous implantation of Lewis-lung-carcinoma-derived different metastatic clones (P29, LM12-3 and LM60-D6 clones with low, medium and high metastatic potentials respectively). Heparan sulphate proteoglycans (125-158 micrograms of hexuronate/g dry weight of tissue) were isolated from chondroitin ABC lyase digests of a proteoglycan fraction obtained after DEAE-Sephacel chromatography of tissue extracts. The proteoglycans were separated into three molecular species by Sepharose CL-4B chromatography followed by CsCl-density-gradient centrifugation: large proteoglycans with an estimated M(r) of 820,000-130,000, which consisted of two components with low (< 1.34 g/ml; PGII-M) and high (> 1.37 g/ml; PGII-B) density, and a small proteoglycan with an M(r) of less than 80,000 (PGIII). Of these, only the PGII-M proteoglycan (34-37 micrograms of hexuronate/g dry weight) reacted with the antiserum against proteoglycan of Engelbreth-Holm-Swarm-tumour basement membrane, and represented, therefore, a basement-membrane proteoglycan. Digestion with heparan sulphate lyases I and II of the heparan sulphates (M(r) 36,000) from the PGII-M proteoglycan of the three tumours resulted in almost complete depolymerization to give six unsaturated disaccharides identified as 2-acetamido 2-deoxy-4-O-(4-deoxy-alpha-L-threo-hex-4-enopyranosyluron ic acid)-D-glucose, 2 acetamido-2-deoxy-4-O-(4-deoxy-alpha-L-threo-hex-4-enopyranosyluron ic acid)-6-O sulpho-D-glucose, 2-deoxy-2-sulphamino-4-O-(4-deoxy-alpha-L-threo-hex-4-enopyrano syluronic acid)-D-glucose, 2-deoxy-2-sulphamino-4-O-(4-deoxy-alpha-L-threo-hex-4 enopyrano syluronic acid)-6-O-sulpho-D-glucose, 2-deoxy-2-sulphamino-4-O-(4-deoxy 2-O-sulpho-alpha-L-threo-hex-4- enopyranosyluronic acid)-D-glucose and 2-deoxy-2 sulphamino-4-O-(4-deoxy-2-O-sulpho-alpha-L-threo-hex-4- enopyranosyluronic acid) 6-O-sulpho-D-glucose. Comparison of the relative amounts of these disaccharides produced from the three tumour-derived heparan sulphates demonstrated that the degree of sulphation of the heparan sulphates correlated with the degree of morphological organization of the tumour basement membranes; the heparan sulphate from the more highly metastatic tumour with more highly organized basement membrane exhibited a higher degree of overall sulphation along the glycosaminoglycan chains, which was due to an increased content of the three repeating disaccharides having 6-O-sulphated glucosamine residues. PMID- 1445267 TI - Isolation and partial characterization of heparan sulphate proteoglycans from human hepatic amyloid. AB - Proteoglycans were isolated from human amyloidotic liver by extraction with guanidine, followed by trichloroacetic acid precipitation, DEAE-Sephacel ion exchange chromatography, and Sepharose CL-6B gel chromatography. A significant portion of the material was found to be free chondroitin/dermatan sulphate chains (30%), whereas the predominant part was heparan sulphate proteoglycan (HSPG) (70%). The approx. molecular mass of the HSPG was 200 kDa, as measured by gel electrophoresis and gel chromatography. The molecular mass of the core protein was shown to be 60 kDa by SDS/PAGE following de-aminative cleavage of the heparan sulphate chains. The heparan sulphate chains were liberated from the core protein by alkali treatment and found to have a molecular mass of approx. 35 kDa by Sepharose CL-6B gel chromatography. The core protein was shown, by immunoblotting, to react with a monoclonal antibody against bovine basement membrane HSPG. The presence of HSPG in amyloid deposits was further confirmed by immunohistochemistry on tissue sections from amyloidotic liver using the same antibody. PMID- 1445268 TI - Partial purification of a 6-methyladenine mRNA methyltransferase which modifies internal adenine residues. AB - Two forms of a 6-methyladenine mRNA methyltransferase have been partially purified using a T7 transcript coding for mouse dihydrofolate reductase as an RNA substrate. Both enzyme forms modify internal adenine residues within the RNA substrate. The enzymes were purified 357- and 37-fold respectively from nuclear salt extracts prepared from HeLa cells using DEAE-cellulose and phosphocellulose chromatography. The activity of the first form of the enzyme eluted from DEAE cellulose (major form) was at least 3-fold greater than that of the second (minor form). H.p.l.c. analysis of the hydrolysed, methylated mRNA substrates demonstrated that both forms of the enzyme produced only 6-methyladenine. The two forms of the enzyme differed in their RNA substrate specificity as well as in the dependence for a 5' cap structure. The 6-methyladenine mRNA methyltransferase activity was found to be elevated in HeLa nuclei as compared with nuclear extracts from rat kidney and brain. Enzymic activity could not be detected in nuclei from either normal rat liver or regenerating rat liver. In the case of the HeLa cell, activity could only be detected in nuclear extracts, with a small amount in the ribosomal fraction. Other HeLa subcellular fractions were void of activity. PMID- 1445269 TI - A recombinant hybrid anaphylatoxin with dual C3a/C5a activity. AB - By site-directed mutagenesis of a human complement factor C5a cDNA clone, we have designed a hybrid anaphylatoxin in which three amino acid residues in the C terminal sequence of human C5a were exchanged to create the native C-terminal human C3a (hC3a) sequence Leu-Gly-Leu-Ala-Arg. This hybrid anaphylatoxin rC5a-(1 69)-LGLAR exhibited true C3a and C5a activity when tested in the guinea pig ileum contraction assay. Quantitative measurements of ATP release from guinea pig platelets revealed about 1% intrinsic C3a activity for this hybrid, while the C5a activity was essentially unchanged. Competitive binding assays confirmed that the rC5a-(1-69)-LGLAR mutant was able to displace radioiodinated rhC5a with a KI of approx. 40 nM and hC3a with a KI of approx. 3.7 microM from guinea pig platelets. Since the C-termini of both human C3a and C5a anaphylatoxins are known to interact with their respective receptors, we conclude that the same peptidic sequence, LGLAR, is able to bind to and activate two different receptors, the C3a receptor as well as the C5a receptor. This clone provides a novel tool for the identification of further receptor-binding residues in both anaphylatoxins, since any mutants may be tested for altered C3a and C5a activity simultaneously. PMID- 1445270 TI - Properties of a partially purified phosphodimethylethanolamine methyltransferase from rat brain cytosol. AB - The presence of cytosolic S-adenosylmethionine-dependent N-methyltransferase(s) activity(ies) capable of converting phosphoethanolamine into phosphocholine has been recently demonstrated in the rat brain. At least two enzymes are involved in the methylation of phosphoethanolamine to phosphocholine and these are separable by ammonium sulphate fractionation. The enzyme catalysing the last step of this methylation process is present in the 50-80% ammonium sulphate fraction. A 220 fold purified enzyme has been obtained with sequentially employed Q-Sepharose fast flow and octyl-Sepharose CL4B column chromatography. The maximum enzyme activity was at pH 9.5. The Km values for S-adenosylmethionine, the methyl donor, and phosphodimethylethanolamine, the methyl acceptor, were 125 microM and 750 microM respectively. This phosphodimethylethanolamine N-methyltransferase was found to be calcium-dependent, with a 4-fold increase in activity at 0.5 mM CaCl2. S-Adenosylhomocysteine at 0.5 mM caused 100% inhibition of the activity. The effects of various structural analogues on the phosphodimethylethanolamine N methyltransferase activity were also investigated and these results suggest that the enzyme is specific to the substrate. These results provide evidence for the existence of the pathway for the methylation of phosphoethanolamine to phosphocholine in rat brain cytosol. PMID- 1445272 TI - The fate of the prosegment in the acute-phase and programmed synthesis of sapecin, an antibacterial peptide of the flesh fly (Sarcophaga peregrina). AB - The nucleotide sequence of sapecin cDNA suggested that this antibacterial peptide of the flesh fly (Sarcophaga peregrina) is produced from preprosapecin by post translational processing. We examined the production of sapecin and its prosegment by radioimmunoassay under two different physiological conditions in which its gene is activated, assuming that the prosegment has some biological role. Results suggested that the prosegment is degraded selectively during production of sapecin. We also found that imaginal discs synthesize sapecin when cultured in the presence of 20-hydroxyecdysone. PMID- 1445271 TI - Functional alterations of type I insulin-like growth factor receptor in placenta of diabetic rats. AB - The presence of type I insulin-like growth factor (IGF-I) receptors on placental membranes led to the hypothesis that these receptors might play a critical role in the rapid growth of this organ. Diabetes induces feto-placental overgrowth, but it is not known whether it modifies IGF-I receptor activity in fetal and/or placental tissues. To answer this question, we have partially purified and characterized placental receptors from normal and streptozotocin-induced diabetic rats. In normal rats, binding of 125I-IGF-I to a 140 kDa protein corresponding to the alpha subunit of the receptor was observed in cross-linking experiments performed under reducing conditions. Stimulation by IGF-I induces the autophosphorylation of a 105 kDa phosphoprotein representing the beta subunit of the receptor. In rats made hyperglycaemic and insulinopenic by streptozotocin injection on day 1 of pregnancy, placental IGF-I receptor-binding parameters were not different from controls on day 20 of pregnancy. In contrast, the autophosphorylation and kinase activity of IGF-I receptors of diabetic rats were increased 2-3-fold in the basal state and after IGF-I stimulation. The present study indicates that the rat placental IGF-I receptor possesses structural characteristics similar to that reported for fetal-rat muscle, and suggests that the high-molecular-mass beta subunit could represent a type of receptor specifically expressed during prenatal development. In addition, it clearly demonstrates that diabetes induces functional alterations in IGF-I receptor kinase activity that may play a major role in the placental overgrowth in diabetic pregnancy. PMID- 1445273 TI - Primary structure and mitochondrial import in vitro of the 20.9 kDa subunit of complex I from Neurospora crassa. AB - The 20.9 kDa subunit of NADH:ubiquinone oxidoreductase (complex I) from Neurospora crassa is a nuclear-coded component of the hydrophobic arm of the enzyme. We have determined the primary structure of this subunit by sequencing a full-length cDNA and a cleavage product of the isolated polypeptide. The deduced protein sequence is 189 amino acid residues long and contains a putative membrane spanning domain. Striking similarity over a 60 amino-acid-residue domain with the M (matrix) protein of para-influenza virus was found. No other relationship with already known sequences could be detected, leaving the function of this subunit in complex I still undefined. The biogenetic pathway of this polypeptide was studied using a mitochondrial import system in vitro. The 20.9 kDa subunit synthesized in vitro is efficiently imported into isolated mitochondria, where it obtains distinct features of the endogenous subunit. Our results suggest that the 20.9 kDa polypeptide is made on cytosolic ribosomes lacking a cleavable targeting sequence, interacts with the mitochondrial outer membrane (in a process that does not require an energized inner membrane), and is imported into mitochondria at contact sites. The 20.9 kDa subunit is then inserted into the inner membrane acquiring a topology similar to that of the already assembled subunit. PMID- 1445274 TI - Immunological detection of degradation intermediates of skeletal-muscle glycogen phosphorylase in vitro and in vivo. AB - Over 95% of the pyridoxal phosphate (PLP) in skeletal is bound to one protein, glycogen phosphorylase. This, and the fact that phosphorylase constitutes approx. 5% of the soluble protein in skeletal muscle, introduce the possibility that PLP might be used as a specific label to identify degradation intermediates of the enzyme. In this investigation, we have developed immunological methods, using a monoclonal antibody to PLP and polyclonal antibodies to phosphorylase, to detect degradation intermediates in vitro and in vivo. We have identified a family of degradation intermediates of glycogen phosphorylase in the high-speed-supernatant fraction of mouse skeletal muscle. These peptides react with both types of antibodies and are in the size and concentration range expected for degradation intermediates in a model in which the committed step is followed by rapid clearance of the products. Changes in amounts of degradation intermediates are examined in physiological or pathological conditions in which the rate of degradation of phosphorylase is altered. PMID- 1445276 TI - Structural comparison between the mitochondrial aralkyl-CoA and arylacetyl-CoA N acyltransferases. AB - The aralkyl and arylacetyl transferases were purified to homogeneity from bovine kidney by a slight modification of a previous procedure. The M(r) of the arylacetyl transferase was estimated to be 33,500 by SDS/PAGE and that of the aralkyl transferase to be 33,750 by a combination of SDS/PAGE and gel-filtration analysis. N-Terminal-sequence analysis indicated a blocked N-terminus for the arylacetyl transferase and gave the following sequence for the aralkyl transferase: M-F-L-L-Q-G-A-Q-M-L-Q-M-L-E-K. Amino acid analysis revealed differences in composition between the two enzymes. Most notable was the fact that the aralkyl transferase had more methionine and leucine. This difference could be partially accounted for by assuming that the methionine-and-leucine-rich N-terminus was missing from the arylacetyl transferase. Chemical cleavage of the two enzymes at methionine residues using CNBr gave rise to several peptides for each enzyme. N-Terminal-sequence analysis of the 8000-M(r) peptide from the arylacetyl transferase gave a sequence with 69% similarity to the 9000-M(r) peptide from the aralkyl transferase. This was taken to indicate a common origin for the two enzymes. PMID- 1445275 TI - Glycation (non-enzymic glycosylation) inactivates glutathione reductase. AB - Non-enzymic binding of sugars to proteins (glycation) is a common biological phenomenon that is increased in diabetes. Most work has been directed towards structural proteins which may be present for many years and would continue to accumulate sugar residues. As glycation is a non-specific reaction, other proteins such as enzymes will also be susceptible to glycation and could well display altered activity. We investigated the effect of various sugars whose concentrations increase in diabetes in insulin-independent tissues on glutathione reductase, an enzyme that maintains the GSH level in cells. Glucose, glucose 6 phosphate and fructose all displayed a time-dependent inhibition of glutathione reductase activity, suggesting that these sugars glycate this enzyme. Aspirin gave some protection against the loss of activity induced by glucose. PMID- 1445277 TI - Effects of insulin and phorbol esters on subcellular distribution of protein kinase C isoforms in rat adipocytes. AB - Effects of insulin and phorbol esters on subcellular distribution of protein kinase C (PKC) isoforms were examined in rat adipocytes. Both agonists provoked rapid decreases in cytosolic, and/or increases in membrane, immunoreactive PKC alpha, PKC-beta, PKC-gamma, and PKC-epsilon. Effects of phorbol esters on PKC alpha redistribution to the plasma membrane, however, were much greater than those of insulin. In contrast, insulin, but not phorbol esters, stimulated the translocation of PKC-beta to the plasma membrane, and provoked changes in PKC zeta redistribution. Neither agonist altered subcellular distribution of PKC delta, which was detected only in membrane fractions. Our findings indicate that insulin and phorbol esters have overlapping and distinctly different effects on the subcellular redistribution of specific PKC isoforms. PMID- 1445278 TI - Cell surface accessibility of GLUT4 glucose transporters in insulin-stimulated rat adipose cells. Modulation by isoprenaline and adenosine. AB - Insulin-stimulated glucose transport activity in rat adipocytes is inhibited by isoprenaline and enhanced by adenosine. Both of these effects occur without corresponding changes in the subcellular distribution of the GLUT4 glucose transporter isoform. In this paper, we have utilized the impermeant, exofacial bis-mannose glucose transporter-specific photolabel, 2-N-4-(1-azi-2,2,2 trifluoroethyl)benzoyl-1,3-bis-(D-mannos- 4-yloxy)-2-propylamine (ATB-BMPA) [Clark & Holman (1990) Biochem. J. 269, 615-622], to examine the cell surface accessibility of GLUT4 glucose transporters under these conditions. Compared with cells treated with insulin alone, adenosine in the presence of insulin increased the accessibility of GLUT4 to the extracellular photolabel by approximately 25%, consistent with its enhancement of insulin-stimulated glucose transport activity; the plasma membrane concentration of GLUT4 as assessed by Western blotting was unchanged. Conversely, isoprenaline, in the absence of adenosine, promoted a time dependent (t1/2 approximately 2 min) decrease in the accessibility of insulin stimulated cell surface GLUT4 of > 50%, which directly correlated with the observed inhibition of transport activity; the plasma membrane concentration of GLUT4 decreased by 0-15%. Photolabelling the corresponding plasma membranes revealed that these alterations in the ability of the photolabel to bind to GLUT4 are transient, as the levels of both photolabel incorporation and plasma membrane glucose transport activity were consistent with the observed GLUT4 concentration. These data suggest that insulin-stimulated GLUT4 glucose transporters can exist in two distinct states within the adipocyte plasma membrane, one which is functional and accessible to extracellular substrate, and one which is non functional and unable to bind extracellular substrate. These effects are only observed in the intact adipocyte and are not retained in plasma membranes isolated from these cells when analysed for their ability to transport glucose or bind photolabel. PMID- 1445279 TI - First determination of the secondary structure of purified factor VIII light chain. AB - The first analysis of the secondary structure of human factor VIII light chain was performed by c.d. spectroscopy. The purification process described in this paper allowed us to obtain the large amounts of purified factor VIII light chains required for c.d. experiments. Since this 80 kDa protein is non-covalently associated with a heavy chain to form the active molecule, isolated factor VIII light chains were obtained after immunoadsorption and dissociation of the immobilized active complexes by EDTA. Furthermore, factor VIII light chains were discriminated from the residual active complexes and the free heavy chains by a final ion-exchange-chromatography step. This f.p.l.c. analysis showed that factor VIII light chains were less electronegative than the active complexes. The results of conformational analysis by c.d. show that the protein possesses a high degree of regular secondary structure (58%) with approx. 22% of alpha-helix and 36% of beta-strand structures. The protein was completely unfolded by 3 M guanidine hydrochloride. The results obtained from the analysis of c.d. spectra were compared with those predicted from three different statistical methods based on amino-acid sequence. The secondary structure information obtained from these methods was in good agreement with the c.d. results. These results were comparable with the secondary structure prediction of ceruloplasmin, a protein known to show sequence identity to factor VIII. PMID- 1445280 TI - Heterogeneity of L-alanine transport systems in brush-border membrane vesicles from rat placenta during late gestation. AB - The placental uptake of L-alanine was studied by using purified brush-border membrane vesicles from rat trophoblasts. Saturation curves were carried out at 37 degrees C in buffers containing 100 mM (zero-trans)-NaSCN, -NaCl, -KSCN, -KCl, or -N-methyl-D-glucamine gluconate. The uncorrected uptake results were fitted by non-linear regression analysis to an equation involving one diffusional component either one or two saturable Michaelian transport terms. In the presence of NaCl, two distinct L-alanine transport systems were distinguished, named respectively System 1 (S-1; Vm1 about 760 pmol/s per mg of protein; KT1 = 0.5 mM) and System 2 (S-2; Vm2 about 1700 pmol/s per mg; KT2 = 9 mM). In contrast, in the presence of K+ (KCl = KSCN) or in the absence of any alkali-metal ions (N-methyl-D-glucamine gluconate), only one saturable system was apparent, which we identify as S-2. When Na+ is present, S-1, but not S-2, appears to be rheogenic, since its maximal transport capacity significantly increases in the presence of an inside-negative membrane potential, created either by replacing Cl- with the permeant anion thiocyanate (NaSCN > NaCl) or by applying an appropriate K+ gradient and valinomycin. alpha-(Methylamino)isobutyrate (methyl-AIB) appears to be a substrate of S-1, but not of S-2. For reasons that remain to be explained, however, methyl-AIB inhibits S-2. We conclude that S-1 represents a truly Na(+) dependent mechanism, where Na+ behaves as an obligatory activator, whereas S-2 cannot discriminate between Na+ and K+, although its activity is higher in the presence of alkali-metal ions than in their absence (Na+ = K+ > N-methyl-D glucammonium ion). S-2 appears to be fully developed 2 days before birth, whereas S-1 undergoes a capacity-type activation between days 19.5 and 21.5 of gestation, i.e. its apparent Vmax. nearly doubles, whereas its KT remains constant. PMID- 1445281 TI - Kinetic analysis of internalization, recycling and redistribution of atrial natriuretic factor-receptor complex in cultured vascular smooth-muscle cells. Ligand-dependent receptor down-regulation. AB - The kinetics of internalization, sequestration and metabolic degradation of atrial natriuretic factor (ANF)-receptor complex were studied in rat thoracic aortic smooth-muscle (RTASM) cells. These parameters were directly determined by measuring 125I-ANF binding to total, intracellular and cell-surface receptors. Pretreatment of cells with the lysosomotropic agent chloroquine and the energy depleter dinitrophenol led to an increase in the intracellular 125I-ANF radioactivity. After 60 min incubation at 37 degrees C, cell-associated 125I-ANF radioactivity fell rapidly in chloroquine-treated cells (> 85%) compared with the controls (< 45%). 125I-ANF radioactivity increased to a peak of 65% of the initial level within 15 min in chloroquine-treated cells compared with only 22% in the control cells. During the initial incubation period at 37 degrees C, chloroquine inhibited the release of both intact and degraded 125I-ANF in a time dependent manner. However, at later incubation times, the effect of chloroquine was diminished and release of both degraded and intact ligand was resumed. Extracellular unlabelled ANF did not affect the release of degraded 125I-ANF but it accelerated the release of intact ANF by a retroendocytotic mechanism. After the endocytosis, about 30-40% of ANF receptors were restored to the cell surface from the internalized pool of receptors. The restoration was blocked by chloroquine or dinitrophenol but not by cycloheximide. Exposure of RTASM cells to unlabelled ANF resulted in a time- and concentration-dependent loss of ANF receptors. Unlabelled ANF (10 nM) induced a loss of more than 52% of 125I-ANF binding, and a complete loss occurred at micromolar concentrations. It is inferred that ANF-induced down-regulation of its receptor resulted primarily from an increased rate in internalization and metabolic degradation of ligand-receptor complex by receptor-mediated endocytotic mechanisms. PMID- 1445282 TI - Oxidation of monohydric phenol substrates by tyrosinase. An oximetric study. AB - The purity of commercially available mushroom tyrosinase was investigated by non denaturing PAGE. Most of the protein in the preparation migrated as a single band under these conditions. This band contained both tyrosinase and dopa oxidase activity. No other activity of either classification was found in the preparation. Oxygen consumption by tyrosinase during oxidation of the monohydric phenol substrates tyrosine and 4-hydroxyanisole (4HA) was monitored by oximetry in order to determine the stoichiometry of the reactions. For complete oxidation, the molar ratio of oxygen: 4HA was 1:1. Under identical conditions, oxidation of tyrosine required 1.5 mol of oxygen/mol of tyrosine. The additional oxygen uptake during tyrosine oxidation is due to the internal cyclization of dopaquinone to form cyclodopa, which undergoes a redox reaction with dopaquinone to form dopachrome and dopa, which is then oxidized by the enzyme, leading to an additional 0.5 mol of oxygen/mol of original substrate. Oxygen consumption for complete oxidation of 200 nmol of 4HA was constant over a range of concentrations of tyrosinase of 33-330 units/ml of substrate. The maximum rate of reaction was directly proportional to the concentration of tyrosinase, whereas the length of the lag phase decreased non-linearly with increasing tyrosinase concentration. Activation of the enzyme by exposure to citrate was not seen, nor was the lag phase abolished by exposure of the enzyme to low pH. Michaelis-Menten analysis of tyrosinase in which the lag phase is abolished by pre-exposure of the enzyme to a low concentration of dithiothreitol gave Km values for tyrosine and 4HA of 153 and 20 microM respectively. PMID- 1445283 TI - Enhanced expression of inhibitory guanine nucleotide regulatory protein in spontaneously hypertensive rats. Relationship to adenylate cyclase inhibition. AB - We have previously shown that the stimulatory effects of guanine nucleotides, N ethylcarboxamide-adenosine and other agonists on adenylate cyclase activity were diminished in aorta and heart sarcolemma of spontaneously hypertensive rats (SHR) [Anand-Srivastava (1988) Biochem. Pharmacol. 37, 3017-3022]. In the present studies, we have examined whether the decreased response of these agonists is due to the defective GTP-binding proteins (G-proteins) which couple the receptors to adenylate cyclase, and have therefore measured the levels of G-proteins in aorta and heart from SHR and their respective Wistar-Kyoto (WKY) controls by using pertussis toxin (PT)- and cholera toxin (CT)-catalysed ADP-ribosylations and immunoblotting techniques using specific antibodies against G-proteins. The labelling with [32P]NAD+ and PT identified a 40/41 kDa protein in heart and aorta from WKY and SHR and was significantly increased in the hearts (approximately 100%) and aorta (approximately 30-40%), from SHR as compared with WKY. Immunoblotting revealed an increase in the levels of the G-protein alpha-subunits Gi alpha-2 and Gi alpha-3 in heart and Gi alpha-2 in aorta, whereas no change in Go alpha was observed in heart from SHR and WKY. On the other hand, no differences were observed in CT labelling or immunoblotting of stimulatory G protein (Gs) in heart and aorta from WKY and SHR. In addition, CT stimulated the adenylate cyclase activity in heart sarcolemma from WKY and SHR to a similar extent. These results were correlated with adenylate cyclase inhibition and stimulation by various hormones. Angiotensin II (AII), atrial natriuretic factor (ANF) and oxotremorine-mediated inhibition was found to be greater in SHR as compared with WKY, whereas the stimulatory effects of adrenaline, isoprenaline, dopamine and forskolin were diminished in SHR aorta as compared to WKY. These results indicate that regulatory protein G(i) is more expressed in SHR, which may be associated with the decreased responsiveness of stimulatory hormones and increased sensitivity of inhibitory hormones to stimulate/inhibit adenylate cyclase activity. It may thus be suggested that the enhanced G(i) activity may be one of the mechanisms responsible for the diminished vascular tone and impaired myocardial functions in hypertension. PMID- 1445284 TI - Secretion by overexpression and purification of the water-soluble Streptomyces K15 DD-transpeptidase/penicillin-binding protein. AB - Though synthesized with a cleavable signal peptide and devoid of membrane anchors, the 262-amino-acid-residue Streptomyces K15 DD-transpeptidase/penicillin binding protein is membrane-bound. Overexpression in Streptomyces lividans resulted in the export of an appreciable amount of the synthesized protein (4 mg/litre of culture supernatant). The water-soluble enzyme was purified close to protein homogeneity with a yield of 75%. It requires the presence of 0.5 M-NaCl to remain soluble. It is indistinguishable from the detergent-extract wild-type enzyme with respect to molecular mass, thermostability, transpeptidase activity and penicillin-binding capacity. PMID- 1445285 TI - Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth-muscle cell proliferation. AB - We investigated the influence of two structurally unrelated inhibitors of matrix degrading metalloproteinases, Ro 31-4724 and Ro 31-7467, on the primary proliferation of smooth-muscle cells from rabbit aortic explants. Both agents inhibited proliferation in a concentration-dependent manner, but did not affect cell viability. Smooth-muscle cells grown out from explants secreted 95 kDa and 72 kDa gelatinase enzymes that were also inhibited in a concentration-dependent manner by Ro 31-4724 and Ro 31-7467. Interstitial collagenase and stromelysin were not detected. We conclude that metalloproteinases are likely to be involved in the initiation of smooth-muscle proliferation. PMID- 1445286 TI - How the EcoRI endonuclease recognizes and cleaves DNA. AB - One popular recombinant DNA tool is the EcoRI endonuclease, which cleaves DNA at GAATTC sites and serves as a paradigm for sequence specific DNA-enzyme interactions. The recently revised X-ray crystal structure of an EcoRI-DNA complex reveals EcoRI employs novel DNA recognition motifs, a four alpha-helix bundle and two extended chains, which project into the major groove to contact substrate purines and pyrimidines. Interestingly, pyrimidine contacts had been predicted based on genetic and biochemical studies. Current work focuses on the EcoRI active site structure, enzyme and substrate conformational changes during catalysis, and host-restriction system interactions. PMID- 1445287 TI - The matrix-degrading metalloproteinases. AB - The matrix-degrading metalloproteinases are an intriguing family of enzymes that have evolved to digest specific extracellular matrix components. The expression of these enzymes is very highly regulated and can be controlled transcriptionally by a number of growth factors, tumor promoters, oncogenes, and hormones. It is suggested that the coordinated regulation of matrix metalloproteinases and their inhibitors by these agents modify the integrity of the extracellular matrix. These modifications may, at least in part, be responsible for mediating the effects of these factors on complex physiological processes. PMID- 1445288 TI - Oscillations and waves of cytosolic calcium: insights from theoretical models. AB - Oscillations in cytosolic Ca2+ occur in a wide variety of cells, either spontaneously or as a result of external stimulation. This process is often accompanied by intracellular Ca2+ waves. A number of theoretical models have been proposed to account for the periodic generation and spatial propagation of Ca2+ signals. These models are reviewed and their predictions compared with experimental observations. Models for Ca2+ oscillations can be distinguished according to whether or not they rely on the concomitant, periodic variation in inositol 1,4,5-trisphosphate. Such a variation, however, is not required in models based on Ca(2+)-induced Ca2+ release. When Ca2+ diffusion is incorporated into these models, propagating waves of cytosolic Ca2+ arise, with profiles and rates comparable to those seen in the experiments. PMID- 1445289 TI - Use of the HPRT gene and the HAT selection technique in DNA-mediated transformation of mammalian cells: first steps toward developing hybridoma techniques and gene therapy. AB - In 1956, I decided to apply my experience in microbial genetics to developing analogous systems for human cell lines, including the selection of mutants with either a loss or gain of a biochemical function. For instance, mutants resistant to azahypoxanthine showed a loss of the HPRT enzyme (hypoxanthine phosphoribosyl transferase), whereas gain of the same enzyme was accomplished by blocking de novo purine biosynthesis with aminopterin, while supplying hypoxanthine and thymine (HAT selection). Using HAT selection, we: (i) genetically transformed HPRT- mutant cells to HPRT+ wild type by using DNA extracted from HPRT+ cells, and (ii) selected HPRT+ hybrid cells by fusing HPRT- D98/AH2 cells with skin cells. These approaches, which we dubbed in 1962 as a 'first step toward gene therapy', contributed to the later development of (i) cell fusion techniques, (ii) the development of monoclonal antibodies, (iii) routine transformation of mammalian cells with cloned genes, and (iv) methods for creating transgenic organisms. PMID- 1445290 TI - A real mouse for your computer. PMID- 1445291 TI - Two reactions are simultaneously catalyzed by a single enzyme: the arginine dependent simultaneous formation of two products, ethylene and succinate, from 2 oxoglutarate by an enzyme from Pseudomonas syringae. AB - A single enzyme isolated from Pseudomonas syringae pv. phaseolicola PK2 simultaneously catalyzed two reactions, namely, the formation of ethylene and succinate from 2-oxoglutarate, at a molar ratio of 2:1. In the main reaction, 2 oxoglutarate was dioxygenated to produce one molecule of ethylene and three molecules of carbon dioxide. In the sub-reaction, both 2-oxoglutarate and L arginine were mono-oxygenated to yield succinate plus carbon dioxide and L hydroxyarginine, respectively, the latter being further transformed to guanidine and L-delta 1-pyrroline-5-carboxylate. We propose a dual-circuit mechanism for the entire reaction, in which the binding of L-arginine and 2-oxoglutarate in a Schiff-base structure generates a common intermediate for two reactions. PMID- 1445292 TI - Double antenna structure of chicken prolactin receptor deduced from the cDNA sequence. AB - Chicken prolactin receptor (cPRLR) deciphered from the cDNA sequence showed a unique double antenna structure in its extracellular domain. The predicted cPRLR preprotein was composed of 831 amino acids and contained a signal peptide and a transmembrane region. The extracellular domain comprised 438 residues, and was divided into two tandemly repeated, highly homologous units, each of which corresponded to the extracellular domains of mammalian prolactin receptors. Both extracellular units of cPRLR possessed two structural features characteristic of the ligand binding units of cytokine/prolactin receptor family, namely two pairs of cysteine residues and a WSXWS motif. These findings strongly suggest that cPRLR contains two repeated ligand binding units, that is a double antenna structure. The cPRLR gene is expressed in a wide range of tissues of laying hen. PMID- 1445293 TI - Fatty acid-enhanced binding of flavin mononucleotide to bacterial luciferase measured by steady-state fluorescence. AB - Bacterial luciferase catalyzes the oxidation of reduced flavin mononucleotide and tetradecanal resulting in the emission of light. We have investigated the interactions of a recombinant luciferase from a terrestrial bacterium Xenorhabdus luminescens with the reaction products, FMN and myristic acid, using steady-state fluorescence spectroscopy. Quenching of the intrinsic fluorescence and FMN fluorescence on binding of FMN to luciferase was found to be greatly stimulated in the presence of myristic acid, corresponding to a reduction of more than 30 fold in the FMN dissociation constant of the enzyme. In addition, the FMN luciferase complex exhibits distinct fatty acid-dependent fluorescence properties. These results indicate that luciferase forms a ternary complex with FMN and myristic acid with a significantly different conformation from that of the binary FMN-luciferase complex. PMID- 1445294 TI - Enhancing effect of wortmannin on muscarinic stimulation of phospholipase D in rat pheochromocytoma PC12 cells. AB - Wortmannin, a specific inhibitor of myosin light chain kinase (MLCK), enhanced carbachol-induced formation of [3H]phosphatidylethanol ([3H]PEt), a marker of phospholipase D (PLD) activity, in [3H]palmitic acid-labeled PC12 cells. The apparent EC50 value was 1.5 microM, and the effect was maximal at 3 microM and slightly attenuated at higher concentration. Wortmannin alone had no significant effect on [3H]PEt formation. The enhancing effect of wortmannin was observed at the initial increasing phase of [3H]PEt formation but not at the subsequent plateau phase. Wortmannin enhanced also phorbol ester-induced PLD activation. Although the precise mechanism remains to be clarified, these results suggest that MLCK may be involved in PLD regulation in PC12 cells. PMID- 1445295 TI - Structural analysis of human pyruvate kinase L-gene and identification of the promoter activity in erythroid cells. AB - The human pyruvate kinase (PK) L-gene is organized in 12 exons over 9.5 kilobases, and the first and second exons are specifically transcribed to the R- and L-type PK mRNA. The 5'-flanking region upstream the first exon has two CAC boxes and four GATA motifs within 250 bp from the translational initiation codon. Comparison with the rat L-gene revealed four well-conserved elements in the region. The transient transfection demonstrated that the 270-bp upstream region was a powerful promoter in K562 cells, whereas deletion of the distal 150-bp sequences, which included three GATA motifs, resulted in drastic reduction of the activity. When the hypersensitive site 2 of the human beta-globin gene locus was joined to the promoter, the activity of the proximal 120-bp region was enhanced. We concluded that the proximal 120-bp region had a basal promoter activity and that the distal 150-bp region acted as an enhancer in erythroid cells. PMID- 1445296 TI - Cloning of a human DNA sequence that restores expression of hepatic functions in a dedifferentiated rat hepatoma cell. AB - In a study of the regulation of gene expression in liver cells, a strain of dedifferentiated cells (C2) derived from the rat hepatoma line H4IIEC3 was transfected with DNA from human liver. After growth of these C2 variants in a glucose-free medium, revertants were selected which were characterized by the expression of a complete set of liver functions. A 4.3 kb human DNA sequence was detected with an Alu sequence probe in cells of four independent revertant clones and was shown to be an extrachromosomal, covalently closed duplex DNA. This molecule, called HALF1 for reversion inducing sequence, was cloned and transfected into C2 cells. Analyses of the transfectants indicated a correlation between the introduction of this cloned genomic human DNA sequence and the recovery of hepatic traits. PMID- 1445297 TI - Cell killing and induction of manganous superoxide dismutase by tumor necrosis factor-alpha is mediated by lipoxygenase metabolites of arachidonic acid. AB - The signalling pathways utilized by tumor necrosis factor-a (TNF) to elicit its actions have been examined in TA1 adipogenic cells. A role for lipoxygenase metabolites of arachidonic acid as mediators of TNF action in the induction of c fos has been described. In this paper we report that acute cytotoxicity elicited by TNF, in the presence of cycloheximide (CHX), also utilizes this pathway since inhibitors of lipoxygenase action fully prevent TNF/CHX killing of several cell lines. Our data reveal that TNF induction of manganous superoxide dismutase (MnSOD) is also dependent upon lipoxygenase activity. Radical scavengers such as NAC and PDTC prevent TNF/CHX-induced cell killing and reduce MnSOD induction by TNF. Therefore, cell death by TNF/CHX treatment occurs via a pathway in which lipoxygenase products directly or indirectly operate via the generation of superoxide anions. PMID- 1445298 TI - Regulation of human cardiac myosin heavy chain genes: the effect of catecholamine. AB - The 5'-flanking regions of the alpha- and beta-cardiac myosin heavy chain (MyHC) genes were excised from the cosmid human genomic clones using Hind III and Xbal for the alpha-MyHC gene, and the Hind III and Hind III sites for the beta-MyHC gene. These fragments were linked to chloramphenicol acetyl transferase (CAT) vector to generate a chimeric fusion gene. These fusion genes were subsequently transfected to neonatal rat cardiac cultured cells to analyze the CAT activity. The alpha-MyHC gene is preferentially expressed as compared to the beta-MyHC. In the presence of norepinephrine (NE) the beta-MyHC gene is remarkably induced (within 24 hours following the addition of norepinephrine to the cardiocyte culture). However, the alpha-MyHC is also induced. Specific alpha andrenergic antagonists such as terazosin (Tz) partially suppressed both the alpha- and beta MyHC genes as revealed by the CAT activity. These findings suggest that catecholamine does activate the human cardiac MyHC genes but does not differentiate the specific expression of either the alpha- or beta-MyHC genes. PMID- 1445299 TI - Glycosylation of annexin I and annexin II. AB - Human placental annexin I and annexin II were shown to be glycosylated by one dimensional affinity blotting with the lectin concanavalin A, which recognizes D mannose and D-glucose residues. Further evidence that annexin I and annexin II are glycosylated was provided by the finding that these proteins incorporated D [2,6-3H]mannose and D-[6-3H]glucose when they were biosynthesized by the human squamous carcinoma cell line SqCC/Y1. Annexin I and annexin II could be rapidly purified from a human placental membrane extract by concanavalin A-Sepharose, which indicated that these proteins contain two biantennary mannosyl residues. PMID- 1445300 TI - Rapid structural changes in nerve fibers evoked by electric current pulses. AB - Using the garfish olfactory nerve, the time-courses of lateral expansion (swelling) and birefringence changes in nerve fibers have been examined at the site of application of electric current pulses. The effects of various chemical agents on these non-electrical signs of rapid structural changes in the nerve fibers have been examined. These studies have shown that a pulse of outwardly directed current through the superficial layer evokes a fast increase, followed by a slow, gradual increase, in the water-content of the nerve fibers. The full significance of these findings in studies of the process of nerve excitation is discussed. PMID- 1445301 TI - Intracellular signal transduction for interleukin-1 beta-induced endothelin production in human umbilical vein endothelial cells. AB - The authors investigated the intracellular signal transduction for interleukin (IL)-1 beta-induced endothelin (ET) production by endothelial cells from cultured human umbilical vein (HUVEC). Cultured HUVEC released immunoreactive (iR)-ET into the media in a time-dependent manner and a significant increase of iR-ET production was observed by the addition of IL-1 beta. The stimulating effect of IL-1 beta on iR-ET production was respectively inhibited by protein kinase C (C kinase) inhibitor (H-7), Ca-calmodulin inhibitor (W-7), cyclic AMP-dependent protein kinase (A kinase) inhibitor (H-8) and tyrosine kinase inhibitor (genistain) in a dose-dependent fashion. The data suggested that intracellular signal transduction for IL-1 beta-induced iR-ET production were via such pathways as C kinase, A kinase, Ca-calmodulin and tyrosine kinase in combination or independently, though possible mediation by other pathways cannot be ruled out. PMID- 1445302 TI - Isolation and primary structure of urotensin II from the brain of a tetrapod, the frog Rana ridibunda. AB - A peptide related to urotensin II has been isolated in pure form from an extract of the brain of the European green frog, Rana ridibunda. The primary structure of the peptide was established as Ala-Gly-Asn-Leu-Ser-Glu-Cys-Phe-Trp-Lys-Tyr-Cys Val and this sequence was confirmed by chemical synthesis. Frog urotensin II contains an additional amino acid residue compared with fish urotensin II peptides but the structure of the cyclic region of the molecule has been fully conserved. The data show that urotensin II is not confined to the caudal neurosecretory system of fish but is present in the central nervous system of a tetrapod. PMID- 1445303 TI - NG-monomethyl-L-arginine causes nitric oxide synthesis in isolated arterial rings: trouble in paradise. AB - Arginine analogs are commonly used as inhibitors of the synthesis of endothelium derived relaxing factor, nitric oxide. However, their effect on nitric oxide levels is rarely measured. Using a chemiluminescence assay for nitric oxide, we found that NG-monomethyl-L-arginine enhanced, rather than reduced, nitric oxide synthesis in pulmonary arterial and aortic rings. NG-monomethyl-L-arginine inhibited relaxation to the endothelium-dependent vasodilator A23187 in aortic but not pulmonary arterial rings. In contrast, N omega-nitro-L-arginine did not stimulate nitric oxide synthesis and it inhibited relaxation to A23187 in all rings. We conclude that NG-monomethyl-L-arginine is a partial agonist for nitric oxide synthesis. PMID- 1445304 TI - Comparison of the aflatoxin B1-8,9-epoxide conjugating activities of two bacterially expressed alpha class glutathione S-transferase isozymes from mouse and rat. AB - The complementary DNAs of rat glutathione S-transferase (GST, EC 2.5.1.18) Yc1 and of mouse Yc were expressed from a prokaryotic expression vector in E. coli. The purified proteins were analyzed for their activity toward aflatoxin B1-8,9 epoxide (AFBO), the reactive intermediate of the fungal mycotoxin aflatoxin B1 (AFB). The mouse Yc isozyme had about 50-fold higher conjugating activity toward AFBO than the rat Yc1 isozyme (144 nmol/mg/min versus 3.3 nmol/mg/min). The rat Yc1 isozyme had specific activities toward 1-chloro-2,4-dinitrobenzene, cumene hydroperoxide and ethacrynic acid of 10.7, 0.98 and 0.92 mumol/mg/min, respectively, whereas the mouse Yc isozyme had specific activities of 5.7, 2.1 and 0.1 mumol/mg/min for these substrates, respectively. These data provide further support for the hypothesis that the constitutive presence of the alpha class GST Yc isozyme in mouse liver protects mice from the hepatocarcinogenic effects of aflatoxin B1. PMID- 1445305 TI - Reduction-driven polypeptide folding by the delta Tt mechanism. AB - Poly(Gly-Val-Gly-Val-Pro), i.e., poly(GVGVP), exhibits composition and solute dependence of Tt, the temperature of the inverse temperature transition at which hydrophobic folding and assembly occur on raising the temperature. Importantly, a means whereby the value of Tt is lowered from above to below the working temperature becomes an isothermal means of driving folding and assembly, i.e., of achieving free energy transduction. Using poly[0.73(GVGVP),0.27(GK[NMeN]GVP)] where [NMeN] indicates N-methyl nicotinamide attached to the epsilon-NH2 of the Lys(K) residue, chemical and electrochemical reductions are found to remarkably lower the value of Tt; reduction can drive hydrophobic folding and assembly as effectively as decreasing ionization. Changing the redox state of a protein becomes yet another means of achieving free energy transduction by the delta Tt mechanism. PMID- 1445306 TI - Cholesterol ozonation products as biomarkers for ozone exposure in rats. AB - Cholesterol, 1, which is present in both the lung lining fluid and cell membranes of lung tissue, reacts with ozone in aqueous systems to give 3 beta-hydroxy-5-oxo 5,6-secocholestan-6-al (2) as the major product. Reaction of 2 with 2,4 dinitrophenyl hydrazine (DNPH) in aqueous solutions, liposomes or lung extracts affords the anti and syn DNPH derivatives of 2 (3b and 3c) and of the rearrangement product 3,5-dihydroxy-B-norcholestane-6-carboxaldehyde (3a). These derivatives also are detected in lung tissue extracts from rats exposed to 1.3 ppm ozone for 12 hr. PMID- 1445307 TI - Non-peptidic anti-AIDS agents: inhibition of HIV-1 proteinase by disulfonates. AB - Based upon an earlier observation that sodium docosanedioate (NaO2C-(CH2)20 CO2NA) weakly inhibits HIV-1 proteinase (IC50 12 microM), we have identified a class of more potent inhibitors (sulfonic acids) of this enzyme which are likewise dianionic at pH 5-6.5. Many of the compounds were moderately strong inhibitors of the enzyme (IC50 40nM-10 microM) and some have previously been shown to have anti-HIV activity in lymphocytes. Proteinase inhibition was dependent on the separation between sulfonate/carboxylate substituents, consistent with the hypothesis that negative charged ends of an inhibitor might form ionic bonds with Arg 8 and Arg 108 located at either end of the substrate binding groove of the enzyme. The binding mode remains to be established by structure elucidation. Results for enzyme inhibition are presented along with structure-activity relationships and evidence for pH dependent inhibition. The general observations reported here may be useful for developing more potent and selective non-peptidic proteinase inhibitors. PMID- 1445308 TI - Flavones are inhibitors of HIV-1 proteinase. AB - Substituted gamma-chromones were found to weakly inhibit HIV-1 proteinase, an important enzyme in the replication and processing of the AIDS virus. Chromones bearing hydroxyl substituents and a phenolic group at the 2-position (flavones) were the most active compounds and structure-activity relationships for a limited series of flavone inhibitors are presented. Dixon plots are reported and a possible mechanism for flavone-induced inhibition is proposed. The results are also compared with those for some structurally related non-peptidic inhibitors of HIV-1 proteinase. Since some flavonoid compounds have already been shown to have antiviral activity against AIDS, the present observations of anti-HIV-1 proteinase activity may be particularly significant. PMID- 1445309 TI - Heat stress of cultured GC cells enhances triiodothyronine-induced growth hormone production by action within the 5'-flanking region of the rat growth hormone gene. AB - We studied the effect of incubation at 41 C on a clone of GC cells that had previously been stably transfected with a gene construct, pGHXGPT, containing 1800 to +8 of the rat growth hormone promoter fused to the structural gene for E. Coli xanthine guanine phosphoribosyl-transferase. The effect of incubation of the clone containing pGHXGPT at 41 C was to enhance triiodothyronine induction of growth hormone secretion (2-fold, p < 0.01) and of xanthine quanine phosphoribosyl-transferase activity (3-fold, p < 0.01). We conclude that the increase in triiodothyronine-induced growth hormone production during heat stress occurs by stimulation of the growth hormone promoter. PMID- 1445310 TI - Processing of atriopeptin prohormone by nonmyocytic atrial cells. AB - Atriopeptin (AP) is synthesized and stored in the mammalian atria as a 126 amino acid prohormone (AP126). Upon secretion, the prohormone undergoes site specific proteolysis within the atria to yield the carboxyl terminal 28 amino acid hormone (AP28). The atrial cell responsible for AP126 bioactivation has not yet been determined. Primary neonatal rat atrial cell cultures were generated with and without depletion of nonmyocytic cells. The molecular form of AP detected in the conditioned media of mixed cultures was determined to be AP126. Addition of dexamethasone to these cultures resulted in the appearance of a peptide that co migrated with AP28. In contrast, no AP126 processing was detected in the conditioned media of myocyte enriched cultures when grown in the presence of dexamethasone. Readdition of nonmyocytic atrial cells to myocyte enriched cultures successfully reconstituted the steroid induced AP126 processing. Incubation of recombinant AP126argarg with nonmyocytic atrial cell cultures resulted in the generation of AP28argarg. We conclude that a nonmyocytic atrial cell is responsible for AP126 processing in vitro. PMID- 1445311 TI - N epsilon(gamma-glutamyl)lysine crosslinks in the blood clot of the horseshoe crab, Limulus polyphemus. AB - Clots were allowed to form in samples of whole blood taken from the American horseshoe crab, Limulus polyphemus, in the absence and presence of dansylcadaverine (16), and were analyzed for their contents of N epsilon(gamma glutamyl)lysine and gamma-glutamyl-dansylcadaverine. Clots obtained without dansylcadaverine yielded significant amounts of N epsilon(gamma-glutamyl)lysine product. Clots formed in the presence of dansylcadaverine yielded only gamma glutamyl-dansylcadaverine. Formation of these products reflects on the activity of transglutaminase released from the blood cells during coagulation. PMID- 1445312 TI - A peptide sequence on carcinoembryonic antigen binds to a 80kD protein on Kupffer cells. AB - Clearance of carcinoembryonic antigen (CEA) from the circulation is by binding to Kupffer cells in the liver. We have shown that CEA binding to Kupffer cells occurs via a peptide sequence YPELPK representing amino acids 107-112 of the CEA sequence. This peptide sequence is located in the region between the N-terminal and the first immunoglobulin like loop domain. Using native CEA and peptides containing this sequence complexed with a heterobifunctional crosslinking agent and ligand blotting with biotinylated CEA and NCA we have shown binding to an 80kD protein on the Kupffer cell surface. This binding protein may be important in the development of hepatic metastases. PMID- 1445313 TI - Interaction of dopamine-beta-monooxygenase with chromaffin granule membrane lipids. AB - The interaction between bovine adrenal medullary dopamine-beta-monooxygenase and liposomes from chromaffin granule membrane lipids as a function of pH, lipid and salt concentration was studied by ultracentrifugation. Efficient adsorption of dopamine-beta-monooxygenase to liposomes occurs in the pH range 5.0-6.5 and at low ionic strength. The adsorption was not detected in the case of apoenzyme. The membrane dopamine-beta-monooxygenase forms a complex with liposomes more effective than soluble does. The data obtained lead to certain conclusions about the specificity of complex between the enzyme and liposomes. PMID- 1445314 TI - Determination of hippocampal protein kinase C using a frozen tissue method: comparison of synaptosomal and total activity in C57BL/6 and DBA/2 mice. AB - A slow freeze/fast thaw tissue preparation gave analogous hippocampal protein kinase C (PKC) activity to a fresh tissue preparation in both C57BL/6 and DBA/2 mice. Both the frozen and fresh preparations demonstrated a 28% reduction in membrane-bound PKC activity in DBA compared to C57 mice which supports our previous findings (14). This DBA-associated reduction was found only in total PKC and not synaptosomal PKC activity suggesting that the PKC difference between C57 and DBA mice may be primarily postsynaptic. This investigation shows that (1) PKC activity obtained from a slow freeze/fast thaw preparation is analogous to activity obtained from fresh tissue and (2) analysis of PKC activity in both a total and synaptosomal preparation may provide additional characterization of PKC differences such as that observed between C57 and DBA mice. PMID- 1445315 TI - The binding of plasminogen fragments to cultured human umbilical vein endothelial cells. AB - Glu-plasminogen, kringle 1-5, kringle 1-3, and miniplasminogen exhibited strong binding to human umbilical vein endothelial cells (HUVEC). On the other hand, no significant binding was obtained with microplasminogen and kringle 4. Kringle 1-5 and miniplasminogen, which both contained kringle 5, specifically inhibited the binding of plasminogen to HUVEC while kringle 1-3 did not. The results implied plasminogen molecule contained at least two binding sites, with which it interacted HUVEC. The stronger binding site was located in kringle 5 and the weaker one was in kringle 1-3. Kringle 4 and the active site domain exhibited no significant binding to HUVEC. The interaction of plasminogen with HUVEC is mainly through binding site on kringle 5. PMID- 1445316 TI - Single-stranded DNA of 5'-upstream region of the rolC gene interacts with nuclear proteins of carrot cell cultures. AB - Using the gel retardation assay, proteins of carrot cells capable of binding to a single-stranded DNA of 5'-upstream region of the rolC gene were found. From competition experiments, these DNA-protein interactions were specific to single stranded nucleotide sequence of Ava S fragment (from -94 bp to +23 bp relative to the transcription initiation site). Methylation interference experiments showed that G residue at the position of -41 bases on the bottom strand was important for DNA-protein binding. This residue was located between CAAT box and TATAA box. Such specific interaction between single-stranded DNA and nuclear proteins may play a role in transcription by RNA polymerase II. PMID- 1445317 TI - Oxidation of nitric oxide by oxygen in biological systems monitored by porphyrinic sensor. AB - A porphyrinic sensor was used to monitor the reaction of nitric oxide (NO) with oxygen. In the absence of biological material, the reaction rate is independent of the initial concentration of NO (zero order) and depends only on O2 concentration (first order). At physiologic concentration of NO and O2, the half life of nitric oxide is in order of minutes and decreased to seconds only in the presence of biological material (intact cells). PMID- 1445318 TI - Selective endothelial growth inhibition by tetracyclines that inhibit collagenase. AB - The potential of angiogenesis inhibitors as therapy for human diseases is limited by a lack of clinically available agents. We investigated the mechanism of the anti-angiogenesis effects of minocycline, a commonly used drug, and several derivatives. Endothelial cell proliferation was inhibited by several of these compounds. We found that inhibition was associated with inhibition of collagenase, did not require antibiotic activity, and was not related to cytotoxicity. Other microvessel-associated cells were unaffected. This endothelial antiproliferative effect is a potential mechanism of the anti angiogenic activity of minocycline. PMID- 1445319 TI - Kinetics of the sodium-dependent glutamine transporter in human intestinal cell confluent monolayers. AB - The intestinal epithelium metabolism of glutamine plays a critical role in inter organ nitrogen flow. Although it is known that glutamine is the primary oxidative energy source and nucleotide precursor in intestinal cells, the luminal uptake of glutamine by the apical surface of enterocytes is poorly understood. In this study we have uncovered the sodium-dependent transporter system responsible for L glutamine uptake by the apical membrane of a human intestinal epithelial cell line. The sodium-dependent Michaelis constant (Km) = 247 +/- 45 microM glutamine, and Jmax = 4.44 +/- 0.65 x 10(-9) mole min-1(mg protein)-1 (37 degrees C). Glutamine shares the transporter with alanine, as demonstrated by unlabeled glutamine inhibition of [3H]alanine uptake kinetics with a purely competitive type inhibition pattern, and glutamine inhibition Ki = 205 +/- 18 microM by Dixon analysis. The inhibition pattern for a series of amino acid analogs indicated that this intestinal apical membrane sodium-dependent transporter for glutamine is distinct from any other transport system found in membranes of non-intestinal cells. PMID- 1445320 TI - Casein kinase II-catalysed phosphorylation of calmodulin is altered by amino acid deletions in the central helix of calmodulin. AB - Calmodulin is phosphorylated by casein kinase II on Thr-79, Ser-81, Ser-101 and Thr-117. To determine the consensus sequences for casein kinase II in intact calmodulin, we examined casein kinase II-mediated phosphorylation of engineered calmodulins with 1-4 deletions in the central helical region (positions 81-84). Total casein kinase II-catalyzed phosphate incorporation into all deleted calmodulins was similar to control calmodulin. Neither CaM delta 84 (Glu-84 deleted) nor CaM delta 81-84 (Ser-81 to Glu-84 deleted) has phosphate incorporated into Thr-79 or Ser-81, but both exhibit increased phosphorylation of residues Ser-101 and Thr-117. These data suggest that phosphoserine in the +2 position may be a specificity determinant for casein kinase II in intact proteins and/or secondary structures are important in substrate recognition by casein kinase II. PMID- 1445321 TI - Tetracyclines inhibit intracellular muscle proteolysis in vitro. AB - Tetracycline antibiotics (TETs) have a recently discovered novel action: inhibition of extracellular metalloproteinase activity, especially that of collagenase and gelatinase. This property, now confirmed in 8 different laboratories using > 40 tissue sources, includes natural and semi-synthetic TETs as well as a chemically modified TET (CMT) devoid of antimicrobial activity. We have used 14C-Tyr biosynthetically labelled intracellular proteins in L-6 myoblast culture as a test system to assess intracellular proteolysis. Starvation accelerates proteolysis, which can be suppressed by agents such as insulin or serum. Minocycline, doxycycline, and CMT all retarded the rate of intracellular protein degradation in a dose dependent manner. These agents also demonstrated marked synergism with insulin. A CMT derivative (pyrazole) stripped of one of its metal chelation sites and lacking anti-collagenase activity, also lost its antiproteolytic effect. CMT at physiologic concentrations (< or = 5 micrograms/ml) had no effect on protein synthesis, but at 15 micrograms/ml (pharmacologic), a suppressive effect was noted. These findings demonstrate that TETs can inhibit protein degradation as well as synthesis in a mammalian muscle derived cell line. PMID- 1445322 TI - Selective inhibition of protein tyrosine phosphatase activities by H2O2 and vanadate in vitro. AB - Acute (10-30 min) treatment of intact rat hepatoma (Fao) cells with H2O2, inhibits in vivo protein tyrosine phosphatase activity. Vanadate markedly potentiates this effect although it has only trivial effects of its own. Here we show that H2O2 inhibits a protein tyrosine phosphatase activity, but not a p nitro phenyl phosphate hydrolysing activity, in cytosolic extracts of these cells. This effect is completely reversed by 10 mM dithiothreitol. Other oxidants have similar inhibitory effects. Vanadate inhibits the protein tyrosine phosphatase activity in vitro, and its effects are additive with those of H2O2. These findings suggest that H2O2 and vanadate interact with the protein tyrosine phosphatases at two independent sites. They also suggest that in intact cells H2O2 has a direct inhibitory effect on protein tyrosine phosphatase activity and an indirect effect of facilitating the entry of vanadate. PMID- 1445323 TI - Identification of sialic acids in cell adhesion molecule, contact site A from Dictyostelium discoideum. AB - It has been believed that Dictyostelium discoideum cell membranes contain no sialic acid. In this study, however, we found that contact site A, the cell adhesion molecule of D. discoideum, is a major glycoprotein containing sialic acids. This suggests that sialic acid in non-reducing terminal plays an important role in the cell adhesion in which contact site A is involved. PMID- 1445324 TI - Insulin and lipogenesis in rat adipocytes. I. Effect of insulin incubation on lipid synthesis by isolated rat adipocytes. AB - To assess the effect of insulin on lipid synthesis in isolated rat adipocytes, cells were preincubated for 3 h with high concentrations (16.6 nM) of the hormone and lipogenesis measured through 14C-acetate incorporation into lipids, analyzing at the same time the activity of some lipogenic enzymes. It was found that insulin induced not only a decrease in the number of insulin receptors but a 30% loss in basal and insulin-stimulated acetate incorporation into total lipids as well as a decrease in the activities of enzymes related to the novo fatty acid synthesis pathway as malic enzyme and glucose-6-phosphate dehydrogenase. PMID- 1445325 TI - Molecular cloning in Escherichia coli, expression, and nucleotide sequence of the gene for the ethylene-forming enzyme of Pseudomonas syringae pv. phaseolicola PK2. AB - The gene for the ethylene-forming enzyme of Pseudomonas syringae pv. phaseolicola PK2 was found to be encoded by an indigenous plasmid, designated pPSP1. The gene for the ethylene-forming enzyme was cloned and expressed in Escherichia coli JM109. Nucleotide sequence analysis of the clone revealed an open reading frame that encodes 350 amino acids (mol. wt. 39,444). In a comparison with other proteins, the homology score for the entire amino-acid sequence of the ethylene forming enzyme of Pseudomonas syringae versus ethylene-forming enzymes from plants and 2-oxoglutarate-dependent dioxygenases was low. However, functionally significant regions are conserved. PMID- 1445326 TI - A 16 amino acid synthetic peptide derived from human C3d triggers proliferation and specific tyrosine phosphorylation of transformed CR2-positive human lymphocytes and of normal resting B lymphocytes. AB - We demonstrate herein that p16, a 16 amino acid synthetic peptide derived from human C3d, which carried LYNVEA sequence of C3d reacting with CR2 and C3d present in trypsin-cleaved C3, triggered "in vitro" and "in vivo" phosphorylations and "in vitro" proliferation of human B lymphocytes, depending on the stage of cell differentiation. Indeed, p16 and C3dT induced "in vivo" tyrosine phosphorylation of pp105 and "in vitro" proliferation only of CR2-positive and not of CR2 negative cell lines. In addition, p16 and C3dT also induced "in vivo" tyrosine phosphorylation of pp100 and "in vitro" proliferation of only small dense resting B lymphocytes and not other B lymphocyte subpopulations nor T lymphocytes. These data suggest that induction of pp100 and pp105 phosphorylation by p16 and C3dT could represent an early event associated with expression of CR2 in the regulation of human B lymphocyte proliferation. PMID- 1445327 TI - HIV-1 protease inhibitors containing statine: inhibitory potency and antiviral activity. AB - Several series of chemically different inhibitors of the HIV-1 aspartyl protease have been described. Nevertheless despite the high in vitro potency showed, in most cases these inhibitors are unable to inhibit viral replication in infected cells. Penetration of the inhibitors across the cell membrane might account for their low antiviral activity. The relationship between inhibitory potency, antiviral activity and chemical structures of a series of oligopeptides containing statine or statine derivatives are presented here. PMID- 1445328 TI - Statine based tripeptides as potent inhibitors of HIV-1 replication. AB - Starting from highly potent HIV-1 protease pepstatine analog inhibitors, we have tried to find the minimum consensus sequence which is necessary to conserve anti protease potency and antiviral activity. We describe here some statine based tripeptides which exhibit high affinity for the protease and are able to inhibit the reproductive cycle of HIV-1 in MT-4-infected cells. PMID- 1445329 TI - Production and ligand-binding characteristics of the soluble form of murine erythropoietin receptor. AB - A recombinant soluble form (sEPO-R) of erythropoietin (EPO) receptor (EPO-R) was produced by Chinese hamster ovary cells and isolated in high yield with the EPO fixed gel. Ligand binding assays were done using three methods; precipitation of sEPO-R radiolabeled EPO complex and competition of sEPO-R for the binding of radiolabeled EPO with the cellular EPO-R. The results showed a Kd of 17 nM which was much lower than those for cellular EPO-R. One N-glycosylation site exists in sEPO-R but the glycosylation did not affect the binding affinity to EPO. A complex with a molecular size that corresponded to a 1:1 complex of EPO and sEPO R was detected. PMID- 1445330 TI - Preferential cyclization of 2,3(S):22(S),23-dioxidosqualene by mammalian 2,3 oxidosqualene-lanosterol cyclase. AB - Kinetic studies on the cyclization of 2,3(S)-oxido and 2,3(S):22(S),23 dioxido[14C]squalene catalyzed by liver oxidosqualene-lanosterol cyclase revealed a specificity (in terms of V/Km) of the enzyme for the diepoxide. The specificity ratio was dependent on the enzyme preparation, i.e. purified or microsomal, and was highest (about 5) with the microsomal enzyme in the presence of supernatant protein factors. These results explain why, in the presence of cyclase inhibitors, the squalene epoxides can be channeled into a cholesterol biosynthesis regulatory pathway via 24(S),25-epoxylanosterol and 24(S),25 epoxycholesterol. PMID- 1445331 TI - Sequence and methylation in the beta/A4 region of the rabbit amyloid precursor protein gene. AB - Alzheimer's disease is characterized by the accumulation of the beta/A4 fragment of the amyloid precursor protein in the hippocampal regions of the brain. We report here the isolation of genomic clones carrying exons 15, 16 and 17 of the beta/A4 coding region of the rabbit amyloid precursor protein gene. The complete sequence of these exons predicts that all three peptides are identical to their human counterparts. An unexpectedly high concentration of CpG dinucleotides seen in exon 15 were conserved and continued into the intron 15 region. MspI/HpaII southern blot analysis revealed the presence of a number of methylated CpG dinucleotides in the cloned region of the gene. These data suggest that the rabbit amyloid precursor protein gene could provide a new and useful model for the study of this important gene. PMID- 1445332 TI - A synthetic peptide corresponding to 86-93 of the human type I IL-1 receptor binds human recombinant IL-1 (alpha and beta) and inhibits IL-1 actions in vitro and in vivo. AB - A synthetic peptide corresponding to 86-93 of the human type I IL-1 receptor and its analogues bound human recombinant (hr) IL-1 (alpha and beta) and inhibited dose-dependently both Con A-stimulated proliferation of mouse spleen cells and hrIL-1 beta-stimulated formation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells in rat bone marrow cell cultures. Furthermore, hrIL 1 beta-induced mouse paw edema was dose-dependently inhibited by systemic administration (ip) of the synthetic peptide. These results suggest that one of the IL-1 binding sites of the human type I IL-1 receptor comes to the region of 86-93 and the synthetic peptide having the ability to bind hrIL-1 (alpha and beta) blocks the biological activities of exogenous hrIL-1 beta and endogenous mouse IL-1. PMID- 1445333 TI - The measurement of activin/EDF in mouse serum: evidence for extragonadal production. AB - Many studies have shown that activin/EDF mediates local physiological events at various sites. In this study, the authors confirmed the presence of activin in mouse serum by high performance liquid chromatography (HPLC) monitored by a specific bioassay. The retention time of the active fraction in HPLC was identical to that of authentic activin A, and the activity was neutralized by follistatin. That the serum activin levels in ovariectomized and aged mice were decreased suggests that the serum activin was generated partly by ovary (35%), but also by extragonadal organs. Activin and inhibin are structurally closely related, and both are involved in many physiological processes including control of follicle stimulating hormone secretion by the pituitary. The regulation of serum activin, however, appeared to differ from that of inhibin. PMID- 1445334 TI - Identification of a highly conserved region at the 5' flank of the phospholamban gene. AB - Phospholamban is a protein that regulates the activity of the sarcoplasmic reticulum Ca(2+)-ATPase. The rat phospholamban gene contains a single intron of 6.5 kilobases which interrupts the 5' untranslated region. Primer extension and nuclease mapping analysis identified a major transcription initiation site 87 nucleotides upstream of the first exon/intron junction. A highly conserved region was identified at the 5' flank of the phospholamban gene. This region contained a TATA motif at position -52 which bound nuclear extract, and a consensus CAAT motif at position -76. This highly conserved region may be important in the regulation of basal transcriptional activity. PMID- 1445335 TI - Analysis of IL-2 functional structure by multiple cysteine substitutions. AB - IL-2 has three cysteine residues. The cysteines at positions 58 and 105 of active IL-2 form an intramolecular disulfide bond while that at position 125 remains as a free form. To evaluate the importance of correct disulfide bond, mutant proteins (muteins) that have triple and double substitutions of cysteines with alanines, namely A58/105/125 and A58/125, were made by polymerase chain reaction method respectively. Thymidine incorporation assay on CTLL-2 cells showed that although these two muteins were only 0.5-2.0% as potent as that of wild type IL 2, they were 50-200 fold more active than A58, a mutein that has substitution of cysteine at position 58 with alanine. Binding inhibition study showed that the relative affinity of muteins A58/125 and A58/105/125 for high affinity IL-2 receptors was 5-25 fold higher than that of A58. These results suggest that the dramatic decrease in the activity of mutein A58 may result from the formation of an incorrect disulfide bond between the cysteines at positions 105 and 125. PMID- 1445336 TI - Atrial natriuretic peptide: direct effects on human red blood cell dynamics. AB - The ability to deform is an important feature of red blood cells (RBCs) for performing their function of oxygen delivery. Little is known about the hormonal regulation of RBC deformability. Here we report that human atrial natriuretic peptide (ANP) acts directly on human RBCs leading to the elevation of local bending fluctuations of the cell membrane. These changes are accompanied by an increase in the filterability of RBCs. These ANP effects were mimicked by cyclic GMP analogues, suggesting modulation of local membrane bending fluctuations and RBC filterability via a cyclic GMP-dependent pathway. The effect of ANP on the mechanical properties of RBCs suggests that ANP may increase the passage red blood cells through capillaries resulting in an improved oxygen delivery to the tissues. PMID- 1445337 TI - Elemental analysis of growth plate cartilage by synchrotron-radiation-induced X ray emission (SRIXE). AB - The elemental composition of growth plate cartilage from calf scapula has been studied by means of SRIXE. X-ray emission spectra were obtained from the resting, hypertrophic and calcified regions of cartilage; then, each element was mapped with a lateral definition of about 10 microns x 10 microns. Evidence was found for a homogeneous distribution of the elements in resting cartilage compared to changes in local concentration of some atoms in the hypertrophic-calcified tissue. In this zone Ca, Sr, Ni, Zn, S, reach the maximal concentration at the calcification front while Cu shows a uniform distribution. A Zn distribution similar to that of the Zn-containing enzyme alkaline phosphatase, the key enzyme of calcification, is found. PMID- 1445338 TI - Stimulation of phospholipase C by a mutationally activated G protein alpha 16 subunit. AB - Alpha 16, a member of the alpha q subfamily of G protein alpha subunits, was recently identified in human hematopoietic cells. In order to elucidate the function of this novel alpha subunit, we cloned and mutagenized its cDNA to obtain a constitutively active protein. COS-1 cells were transfected with both wild-type and mutant cDNAs. Expression was confirmed by immunoblotting using a rabbit antiserum raised against the C-terminal decapeptide of alpha 16. The constitutively activated mutant alpha 16-R186C caused a two-fold increase in the formation of inositol trisphosphate in intact COS-1 cells, while the wild-type alpha 16 subunit had no effect. We conclude that alpha 16 is involved in coupling cell surface receptors of human hematopoietic cells to stimulation of phospholipase C. PMID- 1445339 TI - Identification and preliminary characterization of two human digitalis-like substances that are structurally related to digoxin and ouabain. AB - In order to characterize the structure of endogenous digitalis-like immunoreactive factor (DLIF), we utilized peritoneal dialysis fluid from patients with chronic renal failure as a source of endogenous digitalis-like immunoreactive factor (DLIF), and subjected it to one-step ion exchange chromatography, followed by one step reverse HPLC. Crude dialysis fluid contained 0.09 ng/ml of DLIF, and using Amberlite XAD-2 chromatography we extracted 110 ng of DLIF from 800 ml of dialysis fluid. By applying this partially purified DLIF to our HPLC system, we discerned three peaks of DLIF activity, with retention times of 34, 58 and 63 minutes. The first peak overlapped the elution profile of ouabain, and the third peak co-eluted precisely with digoxin. The second DLIF peak was not in proximity to any of the digitalis-like markers employed. Thus, our results indicate that DLIF isolated from peritoneal dialysis fluid exists in three distinct forms, one of which resembles ouabain, and one which is identical to digoxin. PMID- 1445340 TI - [125I]EXP985: a highly potent and specific nonpeptide radioligand antagonist for the AT1 angiotensin receptor. AB - [125I]EXP985 is the first nonpeptide radioligand with high specific activity for the AT1 angiotensin receptor. The biochemical and pharmacological profiles of this ligand were determined using either ligand-receptor binding techniques in rat adrenal cortical microsomes or cellular Ca2+ mobilization in rat smooth muscle cells. Specific binding with 0.1 nM [125I]EXP985 increased slowly with time reaching an equilibrium at 60 min of incubation (22 degrees C). Scatchard analysis of the inhibition/binding data revealed a single class of binding sites having a Kd of 1.49 +/- 0.06 nM and a Bmax of 3.6 +/- 0.1 pmol/mg protein. These sites were saturable and the ligand-receptor complex dissociated with a t1/2 of 58 min. The binding was inhibited by Ang peptides with the following order of potency and IC50 (nM): Ang II (3.7) > Ang III (69) > Ang I (3650), and by the nonpeptide AT1 receptor antagonist, losartan, with an IC50 of 3.2 nM. PD123177, an AT2 selective antagonist, showed minimal inhibitory effect. Specific binding of [125I]EXP985 was found on rat aortic smooth cells. Ang II-induced Ca2+ mobilization in these cells was blocked by EXP985 in a noncompetitive manner. These data show that [125I]EXP985 (or its unlabeled) is a potent and highly specific radioligand or noncompetitive antagonist which represents a novel tool to further our understanding of the biochemistry of AT1 receptors. PMID- 1445341 TI - Differential regulation of phospholipase A2 by cytokines inhibiting bone formation and mineralization. AB - Treatment of fetal rat calvarial cells with interleukin-1 alpha, tumor necrosis factor-alpha, transforming growth factor-beta 1, or group II phospholipase A2 inhibits the number of bone nodules formed in long-term cultures. These same mediators also inhibit the mineralization of fully developed bone nodules in a time and dose-dependent fashion. The pro-inflammatory cytokines interleukin-1 alpha and tumor necrosis factor-alpha cause a dose-dependent induction of rat calvarial cell phospholipase A2-II mRNA levels, suggesting that their effects on bone formation may be mediated indirectly by activation of this enzyme. In contrast, transforming growth factor-beta 1, which has more potent effects on bone formation than interleukin-1 alpha or tumor necrosis factor-alpha, suppresses basal levels of phospholipase A2-II mRNA, indicating a different mechanism of action for this cytokine. PMID- 1445342 TI - Escherichia coli genes involved in cell survival during dormancy: role of oxidative stress. AB - When Escherichia coli cells reach stationary phase of growth, specific gene products are synthesized that protect cells while dormant. "Aged" cells may remain viable in cultures for years. For example, agar cultures stored for 38 years still had more than 10(5) viable cells/ml. However, when specific mutants were cultured, the population of these mutants dropped sharply after 4-10 days. This defect is termed "Stationary-Phase-Death". Each mutant strain was hypersensitive to near-ultraviolet radiation and other oxidative agents. Bovine catalase rescued many of the mutants from death in dormancy, suggesting that specific gene products protect "aged" cells against oxidative damage. PMID- 1445343 TI - Crystalline beta-cyclodextrin.12H2O reversibly dehydrates to beta cyclodextrin.10.5 H2O under ambient conditions. AB - In contact with mother liquor, crystalline beta-cyclodextrin (beta-CD) hydrate has composition approximately beta-CD.12H2O. If crystals are dried at ambient conditions (18 degrees C, approximately 50% humidity), the unit cell volume diminishes approximately 30 to 50 A3. X-ray structure analysis of a dry crystal (0.89 A resolution, 4617 data, R = 0.059) showed the composition beta-CD.10.5 H2O, with approximately 5.5 water molecules in the beta-CD cavity (7 partially and 2 fully occupied sites) and approximately 5.0 between the beta-CD molecules. The positions of the beta-CD host and of most of the hydration waters are conserved during dehydration, but the occupancies of the waters in the beta-CD cavity diminish. Dry crystals put into solvent re-hydrate to the original form. The mechanism of de- and re-hydration is not evident. PMID- 1445344 TI - c-fos, c-jun and c-myc expressions are not growth rate limiting for the human MCF 7 breast cancer cells. AB - Insulin-like growth factor I (IGF-I) was 3 times more potent in pagating MCF-7 cell proliferation than epidermal growth factor (EGF). IGF-I stimulated c-fos mRNA expression about 5 times less than EGF. Both growth factors were equipotent in inducing c-jun and c-myc mRNA expressions. The protein level of c-Myc correlated with the mRNA level. IGF-I and EGF stimulated the transcriptional activity dependent on the phorbol 12-myristate 13-acetate-responsive element (TRE) to the same extent, when measured by the chloramphenicol acetyl transferase activity of a transiently transfected multiple TRE construct. These results strongly indicate that the expression levels of the measured proto-oncogenes do not correlate with the increase of growth stimulation by IGF-I and EGF and are not growth rate limiting for the human MCF-7 breast cancer cells. PMID- 1445345 TI - Activators of protein kinase C induce p34cdc2 histone H1 kinase stimulation in Swiss 3T3 fibroblasts. AB - Phorbol-12,13-dibutyrate and 1,2-dioctanoylglycerol, activators of protein kinase C (PKC) that stimulate DNA synthesis in serum-deprived Swiss 3T3 fibroblasts, induce histone H1 kinase activity associated with anti-cdc2 immunoprecipitates after a lag period of 15h, a time point close to G1/S boundary of the cell cycle in these cells. Downregulation of PKC does not affect the basal cdc2 kinase activity, but potently inhibits both phorbol dibutyrate- and dioctanoylglycerol induced cdc2 kinase activation. Phorbol dibutyrate induces a dramatic increase in the p34cdc2 protein level as well as the appearance of p35-p36 forms of cdc2 on Western blot. In PKC-downregulated cells, the p34 form of cdc2 remains elevated but p35-p36 forms do not appear upon phorbol dibutyrate stimulation. These results demonstrate that PKC activation leads to cdc2 kinase activation in mitogenically responsive Swiss 3T3 cells, and strongly suggest that both expression of p34cdc2 protein and its posttranslational modification(s) are involved in this process. Western blot analysis of PKC isozymes suggests that either PKC alpha, PKC delta or PKC epsilon may be involved in p34cdc2 kinase activation and mitogenesis. PMID- 1445346 TI - Induction of Krox-20 expression after focal cerebral ischemia. AB - Krox-20 is one of the transcription factors of "zinc finger" family. The expression of Krox-20 was investigated in a rat focal cerebral ischemia model by Northern blot analysis and in situ hybridization. Northern blot analysis showed that ischemia for 30 min which caused little cortical infarction induced a 29 fold increase in Krox-20 mRNA signal exclusively in the ischemic cortex. Ischemia for 90 min which led to large cortical infarction induced Krox-20 mRNA not only in the ischemic cortex but also in the ipsilateral hippocampus. The induction of Krox-20 mRNA was rapid, transient and appeared to be controlled at the transcriptional level, as indicated by nuclear run-on assays. The regional induction of Krox-20 mRNA was further confirmed by in situ hybridization. These results suggest that the expression of transcription factor genes may play a role in the post-ischemic changes of the injured brain. PMID- 1445347 TI - Mutational analysis of third cytoplasmic loop domains in G-protein coupling of the HM1 muscarinic receptor. AB - We measured dose-response curves for carbachol stimulation of phosphatidyl inositol (PI) turnover with mutants of the Hm1 muscarinic cholinergic receptor having various deletions from amino acids 219 to 358 of the large third intracellular (i3) loop (208 to 366). These deletions had only small or no effects on the ability of Hm1 transfected into HEK 293 cells to stimulate PI turnover. This result indicates that only small regions of 9 to 11 amino acids adjacent to trans-membrane domains (TMDs) 5 and 6 can be directly involved in G protein coupling. Point mutations were constructed to test the role of charged amino acids in these junctions. A triple point mutation of Hm1 (E214 A/ E216K/ E221 K), which mimics the charge distribution in Hm2 (negatively coupled to cAMP) over the first 14 amino acids of i3, and a double point mutation in the N terminal junction, K359A/K361A, both failed to affect carbachol stimulated PI turnover. Therefore, charge distribution in the loop junctions appears to play a minor role in G protein coupling of Hm1 in HEK 293 cells. PMID- 1445348 TI - Human trifunctional protein deficiency: a new disorder of mitochondrial fatty acid beta-oxidation. AB - In this paper we report the identification of a new disorder of mitochondrial fatty acid beta-oxidation in a patient which presented with clear manifestations of a mitochondrial beta-oxidation disorder. Subsequent studies in fibroblasts revealed an impairment in palmitate beta-oxidation and in addition, a combined deficiency of long-chain enoyl-CoA hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-oxoacyl-CoA thiolase. The recent identification of a multifunctional, membrane-bound beta-oxidation enzyme protein catalyzing all these three enzyme activities (Carpenter et al. (1992) Biochem. Biophys. Res. Commun. 183, 443-448; Uchida et al. (1992) J. Biol. Chem. 267, 1034-1041) suggested an underlying basis for this peculiar combination of three enzyme deficiencies. We show by means of size-exclusion chromatography that there is, indeed, a deficiency of the multifunctional beta-oxidation enzyme protein in this patient. PMID- 1445349 TI - Multiple cis-acting elements of the proximal promoter region are required for basal level transcription of the H1(0) histone gene. AB - Basal level transcription of the mouse histone H1(0) gene is mediated by 531 base pairs of the promoter region. Deletion of the most distal upstream 80 bp of this fragment reduces transcription to very low values. By in vitro footprinting we demonstrate now that multiple factors bind to the DNA fragment localized between the 80 bp and the cap nucleotide. In addition to the presence of motifs for the binding of SP1, H1-box, H4TF-2 and TATA-box-factors, other not yet described protein-binding elements were identified. Internal deletions in the wild type promoter enclosing these motifs strongly restrict transcription. Furthermore, when one of these motifs was modified by site-directed mutagenesis a strong impairment of transcription followed. Thus for basal level transcription, in addition to the 80 bp distal fragment, cis-acting elements localized in the 450 bp proximal promoter region are required. PMID- 1445350 TI - Intracellular [Ca2+] and K+ and Cl- efflux responses in submandibular cells of neonatal and adult rats. AB - The effects of graded doses (5 x 10(-8) to 10(-5)) acetylcholine on intracellular Ca2+ and on 86Rb and 36Cl efflux were compared in submandibular cell clusters of 1 and 7 day-old and adult rats. Initial Ca2+ peaks were similar at agonists concentrations lower than 10(-7) M but the release of Rb+ and Cl- were smaller in cells of young animals. At higher agonist concentrations, Ca2+ peaks were higher in immature cells; however, initial Cl- (but not Rb+) efflux was similar to that of mature cells. Plateau Ca2+ levels were independent of age and agonist concentrations but the content of Cl- and Rb+ varied greatly and differences between age groups were less evident. These data confirm a dissociation between intracellular Ca2+ levels and Ca(2+)-mediated ion transport in immature salivary cells. PMID- 1445351 TI - In vitro induction of cecropin genes--an immune response in a Drosophila blood cell line. AB - The Drosophila melanogaster cell line mbn-2 was explored as a model system to study insect immune responses in vitro. This cell line is of blood cell origin, derived from larval hemocytes of the mutant lethal (2) malignant blood neoplasm (1(2)mbn). The mbn-2 cells respond to microbial substances by the activation of cecropin genes, coding for bactericidal peptides. The response is stronger than that previously described for SL2 cells, and four other tested Drosophila cell lines were totally unresponsive. Bacterial lipopolysaccharide, algal laminarin (a beta-1,3-glucan), and bacterial flagellin were strong inducers, bacterial peptidoglycan fragments gave a weaker response, whereas a formyl-methionine containing peptide had no effect. Experiments with different drugs indicate that the response may be mediated by a G protein, but not by protein kinase C or eicosanoids, and that it requires a protein factor with a high rate of turnover. PMID- 1445352 TI - PI-specific phospholipase C "alpha" from sheep seminal vesicles is a proteolytic fragment of PI-PLC delta. AB - Phosphatidylinositide-specific phospholipase C enzymes (PLCs) catalyze the conversion of the phosphoinositides to biologically important signal transducing molecules. These enzymes may be grouped into "families" which share similar structures and modes of regulation. The existence of a structurally distinct family of PLC termed "alpha" has been recently called into question. In the current paper we show by immunoblotting experiments that PLC "alpha" from sheep seminal vesicles is recognized by monoclonal antibodies raised against the delta 1 isoform of bovine brain PLC, and appears to be derived from a higher molecular weight band at 85 kDa. We also show that antibodies raised against PLC alpha efficiently immunoprecipitate the 85-kDa PLC delta 1 isoform from bovine brain and Chinese hamster lung fibroblasts. These data provide strong evidence that the PLC alpha from sheep seminal vesicles is a proteolytic fragment of PLC delta 1. Thus, there is still no conclusive evidence for a separate "alpha" class of PLC. PMID- 1445353 TI - Platelet derived growth factor induces c-fos and c-myc mRNA in rat aortic smooth muscle cells in primary culture without elevation of intracellular Ca2+ concentration. AB - Platelet derived growth factor (PDGF) has been shown to induce c-fos and c-myc proto-oncogenes. In the present study, we investigated the effects of genistein, a tyrosine kinase inhibitor, and NiCl2, a Ca2+ influx blocker, on PDGF-induced Ca2+ transient and on expression of c-fos and c-myc mRNA. In the presence of extracellular Ca2+, PDGF induced elevation of intracellular Ca2+ concentration ([Ca2+]i) and increases in c-fos and c-myc mRNA, as detected by reverse transcription polymerase chain reaction (RT-PCR) and Northern hybridization. PDGF induced [Ca2+]i elevation was composed of an initial transient increase (first component) followed by steady state elevation (second component). Genistein (10 microM) blocked the 1st, but not the 2nd, component of [Ca2+]i elevation induced by PDGF. NiCl2 (1 mM) and removal of extracellular Ca2+ inhibited the 2nd, but not the 1st, component. In the presence of 10 microM genistein and 1 mM NiCl2, PDGF induced c-fos and c-myc mRNA, although the [Ca2+]i elevation could be completely blocked by these two agents. These results indicate that elevation of [Ca2+]i is not a prerequisite condition for PDGF to induce c-fos and/or c-myc mRNA in rat aortic smooth muscle cells in primary culture. PMID- 1445355 TI - Molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor transcript. AB - In the present study, we report the molecular cloning and sequencing of an alternatively spliced form of the human thyrotropin receptor (hTSHR) mRNA transcript, which has previously been detected on Northern blot analysis of human thyroid cells. The smaller hTSHR cDNA, designated hTSHR cDNA-I, is approximately 1 kb in size and encodes a protein of 253 amino acids. Comparison of the nucleotide sequence of hTSHR cDNA-I with available hTSHR genomic sequence data reveals that the cDNA-I contains exons 1-8 and unidentified DNA tract, presumably an intron. Thus, the hTSHR cDNA-I encodes for the N-terminal half of the extracellular domain of the hTSHR (approximately 60%). The truncated TSHR-I may be secreted and function as a TSH binding protein. PMID- 1445354 TI - Specific blockade of basic fibroblast growth factor gene expression in endothelial cells by antisense oligonucleotide. AB - The migration and proliferation of endothelial cells play a pivotal role in various vascular diseases. To elucidate the role of endogenous basic fibroblast growth factor (bFGF) produced within endothelial cells on cell growth, we introduced the antisense oligonucleotide complementary to bFGF mRNA into cultured bovine aortic endothelial cells by cationic liposome to block the production of autocrine bFGF. The treatment of the endothelial cells with the specific antisense oligomer efficiently inhibited the synthesis of bFGF with the concomitant suppression of endothelial proliferation, indicating the significant role of bFGF as an endothelial growth promotor. The neutralizing antibody against bFGF had no inhibition on basal DNA synthesis of the endothelial cells, in contrast to marked suppressive action of bFGF antisense oligomer. The results provide the new analytic and therapeutic implications in the use of the antisense methodology for the study of vascular biology. PMID- 1445356 TI - Unusual pressure dependence of the lateral motion of pyrene-labeled phosphatidylcholine in bipolar lipid vesicles. AB - The lateral mobility of a pyrene-labeled phosphatidylcholine probe in liposomes containing archaebacterial bipolar lipids has been studied isothermally as a function of pressure. The pressure-dependence of the probe mobility, R, is found to be slightly positive or zero in the temperature range of 17 - 48 degrees C. At temperatures > 48 degrees C, R becomes negative and decreases with temperature. The data indicate that lateral mobility only becomes appreciable at high temperatures. In addition, the R values obtained with other lipid membranes are much lower than that obtained with bipolar liposomes, implying that the membranes of archaebacterial liposomes are laterally immobile, as compared to other lipid membranes. PMID- 1445357 TI - Models of stratum corneum intercellular membranes: the sphingolipid headgroup is a determinant of phase behavior in mixed lipid dispersions. AB - During formation of the intercellular membranes of mammalian stratum corneum, sphingomyelin and glucosylceramide are converted enzymatically to ceramide. To model in isolation the possible effect of such a lipid modification on the phase behavior of the ensemble, we used proton and deuterium nuclear magnetic resonance to compare an equimolar dispersion of bovine brain sphingomyelin, cholesterol, and perdeuterated palmitic acid (at pH 6.2), with an equivalent dispersion in which bovine brain ceramide was substituted for sphingomyelin. While the sphingomyelin dispersions remain in a homogeneous fluid lamellar phase from 20-75 degrees C under these conditions, those containing ceramide display complex polymorphism. PMID- 1445358 TI - Alternative splicing of the mouse amelogenin primary RNA transcript contributes to amelogenin heterogeneity. AB - A heterogeneous population of amelogenin proteins is derived from a single copy of the mouse amelogenin gene. To investigate the one gene--multiple protein enigma, we designed a study to distinguish between alternative splicing and proteolytic cleavage models. A pulse of [35S]methionine labeling demonstrated that multiple amelogenins are synthesized concurrently, a result consistent with an alternative splicing mechanism. Using reverse transcription and polymerase chain reaction we cloned a segment from the 5' end of a mouse amelogenin mRNA and connected it to a previously isolated abbreviated cDNA clone. Four additional cDNAs derived from alternatively spliced amelogenin mRNAs have been cloned and characterized. The five transcripts encode amelogenins 180, 156, 141, 74, and 59 amino acids in length. PMID- 1445359 TI - Studies of the relationship between cell proliferation and cell death. II. Early gene expression during concanavalin A-induced proliferation or dexamethasone induced apoptosis of rat thymocytes. AB - Several data in the literature suggest that an intriguing relationship exists between cell proliferation and cell death. Accordingly, we studied the early expression of different genes in the same cells, i.e. rat thymocytes, undergoing cell proliferation upon stimulation with Concanavalin A or cell death following dexamethasone treatment. We showed that an early accumulation of c-fos, c-jun and c-myc mRNA occurred in both phenomena but with different kinetics. It can be speculated that the early induction of nuclear oncogenes is necessary to allow the later induction of other genes probably regulated at the transcriptional level by the AP-1 complex and/or by Myc protein. The accumulation of the transcript for another gene, i.e. poly(ADP-ribose)polymerase, an enzyme responsible for posttranslational modifications of several nuclear proteins, could instead be related to chromatin modifications occurring in both processes. PMID- 1445360 TI - Enhanced production of platelet-activating factor in stimulated rat leukocytes pretreated with triacsin C, A novel acyl-coA synthetase inhibitor. AB - Triacsin C, a product of Streptmyces sp. SK-1894, was previously reported as an inhibitor of long chain acyl-CoA synthetase. Pretreatment with triacsin C (500 nM) for 1h enhanced production of platelet-activating factor in rat neutrophils, followed by stimulation with A23187 or fMLP. Amount of lyso-PAF was also augumented. Triacsin C alone did not increase PAF content and did not modulate enzymatic activities of acytransferase, cholinephosphotransferase, acetylhydrolase, acetyltransferase or phospholipase A2. These results suggest that triacsin C might enhance supply of substrate for PAF synthesis, i.e. accumulation of lyso-PAF by interfering reacylation pathway. PMID- 1445361 TI - Characterization of high mobility group protein binding to cisplatin-damaged DNA. AB - cis-Diamminedichloroplatinum (II) (cisplatin, CDDP) is a widely used chemotherapeutic agent. While many tumors are highly responsive to CDDP, certain tumors are resistant to this drug, limiting its efficacy. The anti-tumor activity of CDDP is believed to result from its coordination bonding to chromosomal DNA. Alterations in tumor cell sensitivity to CDDP may result from the presence or absence of protein(s) which specifically recognize CDDP-damaged DNA. We have developed a damaged-DNA affinity precipitation assay that allows the direct identification of cellular proteins that bind to CDDP-damaged DNA. Using this procedure, we have identified several proteins which specifically bind to CDDP damaged DNA. Two of these proteins have been identified as high mobility group proteins (HMG) 1 and 2 in the current report, we have characterized the binding of these proteins to CDDP-DNA. The calculated Kd of binding to CDDP-damaged DNA was 3.27 x 10(-10) for HMG1 and 1.87 x 10(-10) for HMG2. Using highly specific chemical modifying reagents, we have determined that Cys residues play an important role in protein binding. We also observed that HMG2 will bind to DNA modified with carboplatin and iproplatin although to a lesser extent than to DNA damaged with CDDP. Thus, our results indicate that HMG 2 binds with high affinity to DNA modified with therapeutically active platinum compounds. In addition, our findings suggest that thiol groups play an essential role in the binding of HMG1 and HMG2 to CDDP-DNA. PMID- 1445362 TI - Phospholipase A2 activity is not involved in the tumor necrosis factor-triggered apoptotic DNA fragmentation in bovine aortic endothelial cells. AB - Using the arachidonic acid release as a probe of phospholipase A2 activity, we tested the involvement of this enzyme in the TNF-triggered apoptotic cell death in the bovine aortic endothelial cells. We observed that TNF induced a liberation of arachidonic acid from these cells which was comparable to that obtained from the L929 cells. An augmentation of the amount of released arachidonic acid or the reduction of the TNF-stimulated phospholipase A2 activity did not modify the TNF induced DNA fragmentation in the endothelial cells. We suggest that these events are not required for TNF apoptotic cytotoxicity in the endothelial cells. PMID- 1445363 TI - Human neutrophil proteinase 3: mapping of the substrate binding site using peptidyl thiobenzyl esters. AB - A series of peptidyl thiobenzyl esters was used to map the active site of human leukocyte proteinase 3. The steady-state kinetics parameters reveal the following features regarding the substrate specificity of proteinase 3 and its putative active site: (a) the preferred P1 residue is a small hydrophobic amino acid such as aminobutyric acid, norvaline, valine or alanine (in decreasing order of preference); (b) the enzyme has an extended active site; and (c) its active site is similar to that of the related serine proteinases leukocyte elastase and leukocyte cathepsin G. PMID- 1445364 TI - Up-regulation of MSH receptors by MSH in Cloudman melanoma cells. AB - MSH can up-regulate MSH binding capacity of cultured Cloudman melanoma cells in a dose- and time-dependent fashion. Binding is mediated through proteins exhibiting an apparent molecular weight of 50-53kDa, consistent with previous studies implicating them as the principal MSH receptors on Cloudman cells. Pre-incubation of cells with MSH stimulates expression of the receptor proteins both on the plasma membrane surface as well as in internal sites associated with coated vesicles. The effects of MSH are additive with those of UV light, suggesting that UV and MSH might stimulate receptor expression through separate mechanisms. PMID- 1445365 TI - Evidence that a ryanodine receptor triggers signal transduction in the osteoclast. AB - We have investigated the effect of the alkaloid ryanodine on the release of intracellularly stored Ca2+ in response to activation of the osteoclast Ca2+ receptor by the surrogate agonist, Ni2+, Ni2+ (6 mM) in the presence of ethylene glycol bis-(aminoethyl ether) tetraacetic acid (EGTA) (1.2 mM) and valinomycin (5 microM) induced a transient elevation of cytosolic [Ca2+] in fura 2-loaded osteoclasts. This transient was superimposed upon a small steady elevation of cytosolic [Ca2+] induced by the initial application of valinomycin alone. Ryanodine (10 microM) completely abolished such responsiveness. However, cytosolic [Ca2+] transients were restored when osteoclasts were depolarized by the extracellular inclusion of 100 mM-[K+] in the same solution. Thus, we demonstrate a sensitivity of the osteoclast signal transduction system to ryanodine for the first time to our knowledge. PMID- 1445366 TI - Molecular cloning and characterization of rabbit pancreatic triglyceride lipase. AB - Pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) has been cloned from a gt11 cDNA library made from poly A+ RNA of adult rabbit pancreas. Pancreatic lipase (PL) assists the absorption of dietary triglycerides by hydrolyzing them at 1 and 3 positions to free fatty acids and 2-monoacylglycerol in the presence of bile acids and colipase in the intestinal lumen. Since rabbits are classifically used for the study of the diet induced changes in the lipid metabolism, as a prelude to studying the diet and age dependent changes in the expression of this enzyme, a full length PL cDNA clone was obtained from its pancreas. The coding region of rabbit pancreatic lipase cDNA consists of 1407 base pairs contained in an open reading frame encoding 469 amino acids including the 16 that constitute the signal peptide. Northern blot analysis revealed a band around 1.5 kb. When rabbit enzyme is compared to other species, an over all homology of 70-80% was observed at the nucleotide level. High homology in the amino acid sequence and composition is also apparent between rabbit and other species like dog (65%), pig (76%) and rat (63%). Highest homology is found to be around active-site serine. The regions of homology with other species may help to define sites of interaction of lipase with co-lipase. PMID- 1445367 TI - Identification of jun-B as third member in human antioxidant response element nuclear proteins complex. AB - Deletion mutagenesis in human NAD(P)H:Quinone Oxidoreductase (NQO1) gene and transfection studies into mammalian cells identified a segment of DNA designated as human Antioxidant Response Element (hARE) responsible for high basal expression in tumor cells and its induction by beta-naphthoflavone (beta-NF). The twenty four base pairs of the hARE contains an essential cis-element AP1 binding site and has been shown to bind to jun-D and c-fos proteins from mouse hepatoma (Hepa-1) nuclear extract. In the present report, we have identified jun-B as the third major protein in the hARE-Hepa-1 proteins complex observed in the band shift assays. PMID- 1445368 TI - The role of protein kinase C in the induction of nitric oxide synthesis by murine macrophages. AB - The role of protein kinase C (PKC) in the induction of nitric oxide synthesis by interferon-gamma (IFN-gamma) was investigated using two murine macrophage cell lines, J774 and RAW 264.7. Nitric oxide (NO) production was markedly reduced by a PKC inhibitor, Ro31-8220 in a dose-dependent manner. Incubation of cells with IFN gamma resulted in translocation of PKC to the cell membrane. Prolonged incubation of cells with a high concentration of phorbol ester, which down-regulated PKC activity, also reduced nitric oxide production. These findings provide evidence that PKC is involved in the induction of nitric oxide synthesis by IFN-gamma. PMID- 1445369 TI - Isolation of a novel nuclear glycoprotein from pig kidney. AB - A nuclear glycoprotein with an apparent Mr of 66,000 Da has been isolated from pig kidney chromatin after extraction with urea, guanidine-HCl and 2 M NaCl, and some of its structural features have been characterized. It belongs to the group of N-glycosylated proteins, which in the nucleus has so far received little attention. From its monosaccharide composition and recognition by lectins its oligosaccharides appear to be of high mannose and/or hybrid types. Some properties of its protein moiety suggest that it has a role in the packing of the DNA loops in the condensed chromatin. PMID- 1445370 TI - Calcium uptake by liver mitochondria from hypothyroid rats is inhibited in vitro by triiodothyronine. AB - The rate of Ca2+ uptake by liver mitochondria from hypothyroid and euthyroid rats was determined as a function of the mitochondrial membrane potential (delta psi). At large values of delta psi Ca2+ uptake was a linear function of delta psi and its dependence on delta psi was the same in mitochondria from euthyroid and hypothyroid rats. However, at small values of delta psi the rates of Ca2+ uptake for mitochondria from euthyroid or hypothyroid rats deviated slightly from each other. Triiodothyronine (T3), at a concentration of 10 nM, inhibited the rate of Ca2+ uptake in vitro, suggesting that T3 in vivo may regulate mitochondrial Ca2+ transport and thus alter the matrix free Ca2+ concentration, which has control over respiration. PMID- 1445371 TI - Purification and properties of urease from the cyanobacterium Anabaena cylindrica. AB - A purification procedure has been developed by which urease activity in extracts from the cyanobacterium Anabaena cylindrica was enriched 500-fold. The procedure involves MgSO4 precipitation at 55 degrees C and chromatography on hydroxylapatite and diethylaminoethyl sephadex. Its molecular weight was measured by sedimentation equilibrium in an airfuge to be 197,000 +/- 2000 with an estimated subunit molecular weight of 32,000 as determined by polyacrylamide gel electrophoresis. The pH- and temperature-dependence of the enzyme were determined and the activity found to be optimal at pH 8 and 30 degrees C, respectively. The concentration-dependence of the activation of the enzyme by Mg++ was measured, as were the effects on activity of a range of other metal ions. PMID- 1445372 TI - Effect of endotoxin on rat liver regeneration after partial hepatectomy. AB - Lipopolysaccharide administered intraperitoneally to rats just after partial (70%) hepatectomy at the dose from 0.04 to 4 mg/kg body weight inhibited the induction of thymidylate synthase and thymidine kinase which are rate-determining enzymes of DNA synthesis, resulting in the impairment of DNA synthesis in the regenerating liver. This effect may be due to the hepato-toxic nature of endotoxin. PMID- 1445373 TI - Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit. AB - An electrophoretic variant of lactate dehydrogenase-A (M) subunit was discovered in a patient with multiple myeloma. DNA analysis of the variant allele revealed a nucleotide substitution (transition) of C to T at codon 314 (CGT-TGT), and this mutation resulted in the replacement of an arginine by a cysteine (R314C). This amino acid replacement affects the net charge of the subunit and makes the LDH-A variant have a faster electrophoretic mobility. The responsible missense mutation created a new restriction site, AGGCCT, which can be simply detected by endonuclease AatI digestion. In addition, four synonymous substitutions with no amino-acid replacements were found at codons 51, 119, 163 and 175 in the LDH-A gene from the patient. PMID- 1445374 TI - Age-specific development of malate-aspartate shuttle in the liver and kidney of mice. AB - The activities of malate-aspartate shuttle enzymes were measured in the liver and kidney of 15-, 30-, and 60-day old mice. The results indicate that the activities (U/mg protein) of both isoenzymes (cytosolic and mitochondrial) of both malate dehydrogenase and aspartate aminotransferase are significantly higher in the liver of 15-day old mice than in the liver of 30- and 60-day old animals. However, the shuttle enzymes showed a peak value in the kidney of 30-day old mice. In vitro reconstitution of malate-aspartate shuttle showed a similar pattern of activity in the tissues studied. These findings suggest that the activity of malate-aspartate shuttle is expressed differentially in these tissues of mice at different postnatal ages. PMID- 1445375 TI - Changes in ADP-ribosylation of rho-related protein by exoenzyme C3 from Clostridium botulinum with maturation in rat testis. AB - A rho-related protein, which was ADP-ribosylated by exoenzyme C3 from Clostridium botulinum, was found in both cytosol and membrane fractions of the testes of adult rats. This protein was observed in the cytosol fraction of the testes already in the newborn, did not significantly change in level up to about 7 weeks, and thereafter became clearly reduced. In the membrane fraction, in contrast, the protein was not found in the newborn rats. These observations suggest that there are some relationships between the maturation of the testes and changes in the subcellular distribution of this rho-related protein. PMID- 1445376 TI - Six-base deletion occurring in messages of human cytochrome P-450 in the CYP2C subfamily results in reduction of tolbutamide hydroxylase activity. AB - We isolated and expressed a clone, hPA6, possibly corresponding to the CYP2C9 cDNA. Compared with the other CYP2C9 cDNA clones, hPA6 showed a 6-nucleotide deletion near its middle. From the same cDNA library, we could also isolate another cDNA clone, named hPA22, which retained the 6 bases. For clarification of the effect of the 2-amino acid deletion resulting from the 6-base deletion on enzymatic activities, both clones were expressed in yeast. The expressed enzymes showed tolbutamide hydroxylase activities, and these activities were inhibited by antibodies against P-450-HM2, a probable CYP2C9. The activity of the enzyme encoded by hPA6 was lower than that encoded by hPA22; thus the 2-amino acid deletion in the CYP2C9 reduced the enzymatic activity. PMID- 1445377 TI - Cell proliferation-related production of matrix metalloproteinases 1 (tissue collagenase) and 3 (stromelysin) by cultured human rheumatoid synovial fibroblasts. AB - We investigated the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and insulin on the cell proliferation of and the production of matrix metalloproteinases (MMPs) by rheumatoid synovial fibroblasts in order to determine the role of these agents in rheumatoid arthritis. PDGF stimulated rheumatoid synovial fibroblasts to increase DNA synthesis and the production of precursor forms of MMP-1 of M(r) = 53,000 and -3 of M(r) = 57,000. EGF and insulin also increased DNA synthesis and the production of these enzymes, but the amount of DNA or MMPs was smaller than that induced by PDGF. Since the production of matrix macromolecules and their degradation is essential for the remodelling of synovial tissue in rheumatoid arthritis, these data suggest that the production of MMP-1 and-3 by rheumatoid synovial fibroblasts in relation to cell proliferation plays an important role in the pathological process of rheumatoid arthritis. PMID- 1445378 TI - Decrease in immunoreactivity and vasoactivity of endothelin-1 after exposure to oxygen. AB - Endothelin-1 (ET-1) caused a dose-dependent contraction of porcine coronary arterial rings. Preincubation of ET-1 in oxygenated Krebs solution at 37 degrees C resulted in a progressive loss of the contractile activity and immunoreactivity of ET-1. The half-life of ET-1 contractile activity in oxygenated and non oxygenated buffer was 16.1 and 86.6 min., respectively. The molecular weight of ET-1 exposed to oxygen was identical to that of ET-1. These results indicate that during the contraction of smooth muscle preparations the levels of ET-1 in the tissue bath are steadily decreasing due to exposure to high pO2 levels. PMID- 1445379 TI - Purification and partial characterization of a trypsin inhibitor from chick skeletal muscle. AB - A protein capable of inhibiting trypsin and a number of other serine proteases was purified from chicken skeletal muscle. It has an apparent molecular weight of 64,000 as determined by gel filtration. The inhibitor molecule binds trypsin at a molar ratio of 1:1 to form a stable complex, in which trypsin can be completely inhibited. In this complex, the inhibitor is extensively digested by trypsin but retains its inhibitory activity and tertiary structure by intramolecular disulfide bonds. In addition, its activity was found to markedly increase during development of embryonic muscle. The physiological role of this inhibitor, however, remains unknown. PMID- 1445380 TI - Cu(2+)-induced lipid oxidation in plasma: questionable relation between cholesterol oxidation and LDL modification. AB - Oxidatively modified low-density lipoproteins (LDL) may be involved in the process of cholesterol deposition in arteries. Because of their cytotoxicity, oxysterols resulting from cholesterol oxidation could be a contributing factor in this process. Studies in this area have generally been performed on purified LDL, but in our research whole plasma was exposed to the oxidizing action of copper. Oxidation of the ring structure, which is at the origin of oxysterols, apparently occurs once most polyunsaturated fatty acids have disappeared. Hydrated LDL density reaches a value identical to that obtained during oxidation of LDL by endothelial cells, whereas the ring structure remains unmodified. PMID- 1445381 TI - Allosteric activation by nucleotides of the inactive by phosphatase ornithine decarboxylase of Escherichia coli. AB - ODC was purified to homogeneity from E. coli K12 MG1655 strain transformed with a pBR322 plasmid carrying the ODC gene. This preparation was homogeneous as it was analyzed by SDS-polyacrylamide gel electrophoresis. From this preparation the amino-terminal sequence analysis was obtained. The native ODC of E. coli is activated by ATP, GTP, CTP and UTP at 10(-3) M concentration to around 170-300%. Our results indicate that the recombinant ODC is activated only by GTP and UTP at 10(-3) M 370% and 300%, respectively. When the recombinant ODC was incubated with calf intestine alkaline phosphatase, this inactive ODC can be reversibly activated allosterically only by GTP or UTP at a concentration of 10(-6) or 10( 5) M. That GTP or UTP can allosterically convert the inactive form of ODC to an active form suggests that these analogues may be the in vivo physiological regulators of ODC. PMID- 1445382 TI - Characterization of bovine heparin-binding neurotrophic factor (HBNF): assignment of disulfide bonds. AB - The topology of the disulfides in native heparin-binding neurotrophic factor (HBNF) isolated from bovine brain was studied by proteolytic digestion using trypsin, Asp-N endoproteinase and chymotrypsin and peptide mapping. Disulfide linked peptides were identified by automated Edman degradation. It has been shown that there are disulfide bonds between Cys15-Cys44, Cys23-Cys53, Cys30-Cys57, Cys67-Cys99 and Cys77-Cys109. PMID- 1445383 TI - Studies on variations of glycoproteins and lysosomal hydrolases in human uterine cervical carcinoma. AB - Variations of glycoprotein components such as hexose, hexosamine, and sialic acid and lysosomal glycosidases such as beta-D-glucosidase, beta-D-galactosidase, and N-acetyl-beta-D-glucosaminidase were studied in the tumor tissue from various stages of cervical carcinoma of the uterus. Carbohydrate components of glycoprotein were found to be markedly reduced, and the reduction was very much significant in hexosamine and sialic acid in the advanced stages. Lysosomal glycosidases exhibited a significant increase, and among them N-acetyl-beta-D glucosaminidase exhibited a prominent increase, in the advanced stages of cervical carcinoma of the uterus. PMID- 1445384 TI - Occurrence of free D-aspartic acid in marine macroalgae. AB - The biologically rare D-aspartic acid was found in extracts of marine macroalgae. DL-aspartic acid was isolated from the Phaeophyta, Hizikia fusiformis, by ion exchange chromatography, and crystallized from aqueous ethanol. It was characterized by optical-rotatory-dispersion analysis and reversed-phase HPLC analysis. The crystal consisted of equal amounts of D and L isomers. The presence of free D-aspartic acid was verified in 15 species from among 20 species of marine macroalgae by the same method (HPLC). Generally, Phaeophyta contained a high concentration of D-aspartic acid in contrast with the low concentration in Phycophyta and Rhodophyta. Particularly in Costaria costata, Hizikia fusiformis and Sargassum yezoensis, belonging to Phaeophyta, D-aspartic acid was found in concentrations proportional to those of L-aspartic acid. PMID- 1445385 TI - Anticoagulant action of rare earth metals. AB - Some of the lanthanides, the rare earth metals, lanthanum (La), cerium (Ce), neodymium (Nd), samarium (Sm), terbium (Tb), dysprosium (Dy), erbium (Er) and ytterbium (Yb) prolonged the clotting time of normal human plasma in a dose dependent manner when clotting was induced either by thromboplastin or by kaolin in the presence of cephalin and Ca2+. They also prolonged the activated factor X induced clotting time of platelet-rich plasma. The amidolytic activities of activated factor X and thrombin progressively decreased with increasing amount of rare earth metals. These results suggested that the rare earth metals appear to show their anticoagulant effect with mechanisms in part the inhibition of the enzymatic activities of both activated factor X and thrombin. PMID- 1445386 TI - Action of a nuclease from rat nuclei on UV-irradiated DNA. AB - An Mg(2+)-dependent nuclease was highly purified from rat-liver nuclei. The nuclease activity was enhanced in ultraviolet light (UV)-irradiated dsDNA, but not in unirradiated dsDNA. Irrespective of UV irradiation, ssDNA was readily cleaved by this enzyme. UV-irradiated plasmid DNA was incubated with this enzyme and subjected to the template primer activity assay with a Klenow polymerase. With increasing incubation time, the activity was enhanced in the circular relaxed and linear forms, but not in the superhelical form. These results implied that this enzyme excises UV-damaged sites in dsDNA to form single strand gaps for repair synthesis. PMID- 1445387 TI - Insulin and IGF1 receptors in a model renal epithelium: receptor localization and characterization. AB - Insulin and IGF1 stimulate transepithelial Na+ transport in the urinary bladder of the toad Bufo marinus, a model renal epithelium. The signal transduction mechanisms for the natriferic action are unknown. Ultrastructural techniques were used to localize both receptors and ligands in the epithelium. Electron microscopy using gold-labelled anti-insulin or anti-IGF1 receptor antibodies demonstrated the majority of the insulin receptors were associated with the basolateral membrane while IGF1 receptors were found on basolateral and apical membranes. Both insulin and IGF1 receptors were found in endosomes and on the membranes surrounding subapical granules. In intact tissues incubated with iodinated IGF1 or insulin, both ligands were associated with the basolateral membrane. IGF1 was internalized to a greater extent than insulin and only IGF1 accumulated in cell nuclei. PMID- 1445388 TI - Polymeric ovotransferrin and its ability to bind and deliver iron to chick-embryo red blood cells. AB - Polymeric forms of hen ovotransferrin have been obtained by storage at 4 degrees C for 5 years or at 57 degrees C for 14 days and fractionated as dimers and tetramers by gel filtration on Sephadex. The ability of tyrosine to undergo nitration was reduced in the tetrameric protein, so that one could hypothesize that dityrosine formation is somewhat responsible of such polymerization process. Experimental data on the biological functionality showed that: i) dimeric ovotransferrin was able neither to bind nor to deliver iron; ii) tetrameric ovotransferrin was able to bind but not to deliver iron. PMID- 1445389 TI - Cholera toxin diminishes tyrosine kinase activity of the insulin receptor. AB - We have examined the effect of cholera toxin (CT) on the insulin receptor tyrosine kinase. Incubation of intact rat hepatoma cells FaO with CT (1 microgram/ml/2h) inhibited insulin-induced receptor autophosphorylation by 30% in vivo. This effect persisted after receptor purification in vitro. CT did not alter hormone binding of the insulin receptor, indicating that the toxin affects signal transduction of insulin at the level of the receptor kinase. Experiments using chinese hamster ovary (CHO) cells transfected either with the human insulin receptor (HIR) or a mutant lacking the last 43 amino acids of the receptor beta subunit (HIR delta CT) showed, that the carboxy-terminal tail of the insulin receptor does not play a role in the suppressive effect of the toxin on the insulin receptor kinase. PMID- 1445390 TI - Relationship between Ca2+ and L-asparagine in the induction of ornithine decarboxylase in H-35 rat hepatoma cells. AB - The activity of ornithine decarboxylase (ODC) in H-35 hepatoma cells depleted of Ca2+ by washing with 2 mM EGTA increased 35-fold after incubating for 4 h in a simple salt-glucose solution containing 10 mM L-asparagine and only if Ca2+ was replenished. Actinomycin D (5 micrograms/ml) and cycloheximide (20 microM) reduced the stimulatory effect by 84 and 100% respectively. Increase of active enzyme protein was also demonstrated by a 3-fold increase in alpha difluoromethylornithine binding. Asparagine prolonged the half-life of induced ODC by 20% whereas Ca2+ reduced it by 32%. The observed inductive effects are not accounted for entirely by a direct influence of Ca2+ and asparagine on the turnover of ODC protein. These factors are likely to be parts of a signalling pathway leading to amplification of cellular ODC. PMID- 1445391 TI - Detection and characterization of mRNA and proteins encoded by human rab2 low molecular weight GTP-binding protein gene. AB - Three RNA species of 3.5, 2.4 and 1.4 kb were detected in all human hematopoietic, fibroblastic and tumor cell lines examined, as the mRNA of human rab2 gene presumably involved in intracellular transport. The mRNA differed in the length of the 3'-non-translated regions due to termination and/or processing at the alternative polyadenylation sites. The 1.4-kb rab2 RNA was predominant in Molt-4 and U-937 of mononuclear cell origin, while the 2.4-kb RNA was dominant in the other cells examined. The degradation of all rab2 RNA was similar and as slow as beta-actin RNA. The rab2 proteins were ubiquitously detected in the human cells as two phosphorylated peptides of major pp24rab2 and minor pp25rab2. pp25rab2 was slightly more phosphorylated than pp24rab2. Both rab2 proteins were abundantly detected in neural PC12 and NB3 cells, and mostly pp24rab2 was produced in the other human and rodent cells. PMID- 1445392 TI - Urea synthesis in rats fed diet containing kidney beans. AB - When rats were fed a diet containing kidney bean (Phaesolus vulgaris) urea excretion was increased 3-5 fold. Isolated liver mitochondria from rats fed the kidney bean diet produced 40% more citrulline in the presence of arginine than mitochondria isolated from control rats. Mitochondrial activities of urea cycle enzymes and N-acetylglutamate synthetase were similar in animals fed diets containing kidney bean or lactalbumin. The possible mechanisms causing acute urea production in rats fed with kidney bean are discussed. PMID- 1445393 TI - Interactions between the dopamine D2 receptor and GTP-binding proteins. AB - The dopamine D2 receptor in bovine brain striatum exists in a high- and a low affinity state for dopamine. The high-affinity state is believed to arise from coupling with a guanine nucleotide-binding protein, to be disrupted by the addition of GTP. We found that antibodies specific to the C-terminal region of the alpha-subunit of Go and Gi cause a shift from high- towards low-affinity, demonstrating that the C-terminus of G alpha is involved in the receptor G protein contact. Purification of the D2 receptor by affinity chromatography via immobilized agonists or antagonists results in the copurification of both Go and Gi proteins. However, this copurification is of a nonspecific nature and prevents the detection of putative specific receptor.G protein complexes. PMID- 1445394 TI - Changes in membrane fluidity during human liver development. AB - The physico-chemical properties of the hepatic plasma membrane during prenatal period of development and in adult human liver were studied. Fluorescence polarization studies using the lipid probe pyrene, clearly demonstrated a significant reduction in the membrane fluidity with liver maturation. Lipid analysis showed an age dependent reduction in lipid/protein ratio while there was an increase in membrane cholesterol throughout the prenatal period and in adult human liver which decreased the membrane fluidity. Hepatic plasma membrane from prenatal liver also showed a decrease in phosphatidyl choline/phosphatidyl ethanolamine ratio and an increase in sphingomyelin/phosphatidyl choline ratio. These results suggest that there is a gradual decrease in lipid content and membrane fluidity during the prenatal period of development which might regulate the differentiation of membrane associated function in human liver. PMID- 1445395 TI - Relationship between serum lipid peroxidation products in hypercholesterolemic subjects and vitamin E status. AB - The relationship of serum lipid peroxidation products in hypercholesterolemic subjects to their vitamin E intake was examined in 15 such subjects with no other associated significant disease process in a 3 month trial with vitamin E supplementation. These patients with elevated serum cholesterol levels also have elevated thiobarbituric acid reactive substances (TBARS) and lipid oxidation products (LOPS). Vitamin E supplementation of 800 IU daily normalized the lipid peroxidation products but did not significantly change serum lipids. PMID- 1445396 TI - Purification and characterization of N-acetyl-alpha-D-galactosaminidase from Gallus domesticus. AB - Exoglycosidases modify carbohydrate epitopes on glycoproteins and glycolipids. The N-acetyl-alpha-D-galactosaminidase from the domestic chicken, Gallus domesticus, is an important exoglycosidase which degrades the human blood group A epitope. This enzyme has never been demonstrably purified or thoroughly characterized. We have developed a technique to purify this enzyme to homogeneity. The isolated enzyme has a molecular weight of 49.1 kDa by SDS PAGE and 145.0 kDa by gel filtration. The enzyme is highly selective for PNP-N-acetyl alpha-D-galactosaminide and is inactive against other low molecular weight substrates. The enzyme hydrolyzes the terminal N-acetyl-alpha-D-galactosaminide residues from blood group A2 erythrocytes. Protease activity is below detectable limits. The enzyme has a pH optima of 3.7, a pI of 8.15, is relatively unaffected by ionic strength, and is stable at 4 degrees C. PMID- 1445397 TI - Purification of a membraneous actin binding protein from bovine adrenal medulla. AB - An actin binding protein having a molecular mass of 39,000 was purified from the Triton extract of bovine adrenal medulla membrane fraction using DNase I affinity column and following chromatographies. Specific antibody was produced against the protein and immunoblotting analysis of tissue extract showed the purified protein was not a breakdown product of a larger protein and also showed the presence of this protein in bovine adrenal medullary chromaffin cells and rat pheochromocytoma cells (PC12). An immunoblotting analysis of membrane fractions treated with nucleotides and their analogues showed that this protein was specifically solubilized in the presence of GTP gamma-S. PMID- 1445399 TI - The Archaebacteria: biochemistry and biotechnology. PMID- 1445398 TI - Purification and properties of 2,3-dihydroxy-p-cumate-3,4-dioxygenase from Bacillus species. AB - 2,3-Dihydroxy-p-cumate-3,4-dioxygenase, an enzyme involved in the catabolism of p cymene, was purified to homogeneity from Bacillus species by affinity chromatography. Purification of the dioxygenase allowed the observation of the immediate ring cleavage product of 2,3-dihydroxy-p-cumate. The enzyme was optimally active at pH 8.2 and at 35 degrees C. The Km value for 2,3-dihydroxy-p cumate was 32 microM. The enzyme had a broad substrate specificity for 3 substituted catechols. The activity of the enzyme was inhibited by heavy metals, sulphydryl inhibitors, iron-chelating agents, and substrate analogues. Fe2+ was suggested as a cofactor. PMID- 1445400 TI - What are the archaebacteria and why are they important? PMID- 1445401 TI - Halophilic malate dehydrogenase--a case history of biophysical investigations: ultracentrifugation, light-, X-ray- and neutron scattering. AB - Halophilic malate dehydrogenase (hMDH) from Haloarcula marismortui has been isolated, purified and characterized by biochemical and biophysical solution studies. A stabilization mechanism at extremely high concentrations of salt, based on the formation of co-operative hydrate bonds between the protein and hydrated salt ions, was suggested from thermodynamic analysis of native enzyme solutions. Recently the gene coding for hMDH was isolated and sequenced and an active enzyme cloned (F. Cendrin, J. Chroboczek, G. Zaccai, H. Eisenberg and M. Mevarech, unpublished work). A study of the crystal structure of hMDH in a high salt physiological medium is in progress (O. Butbul-Dym & J. Sussman, personal communication). Here we discuss in depth implications of these recent developments on our earlier results. PMID- 1445402 TI - Proteins from hyperthermophilic archaea: stability towards covalent modification of the peptide chain. PMID- 1445403 TI - Biotechnological potential of halobacteria. AB - The extremely halophilic archaebacteria (halobacteria) became an early focus of scientific interest owing to their role in salted food deterioration. In more recent times their peculiar physiology involving extreme adaptation to the salt environment and other unique features have allowed the development of other applied interests. Their similarities to eukaryotic cells at the level of cell division justifies their use in the prescreening for anti-cancer drugs, and some of their antigens could be used for cancer diagnosis. Their unique retinal proteins can be used as light-biosensors and the use of the purple membrane (pm) as reversible holographic medium has already been developed. Halobacterial enzymes are an extremely tough raw material for enzyme technology, particularly for applications in which the reaction mixture has very low water activity. Thanks to their peculiar lipids and to the production of polysaccharides by some halobacteria, their cultures could be used for enhanced oil recovery. Some halobacteria are excellent producers of industrially interesting biopolymers. The use of halobacteria as producers of polyhydroxyalkanoates, biological polyesters such as poly-3-hydroxybutyrate, with the properties of biodegradable thermoplastics, is being considered. PMID- 1445404 TI - Enzymes from thermophilic archaebacteria: current and future applications in biotechnology. AB - The one guaranteed property of enzymes isolated from extremely thermophilic micro organisms is their thermostability. Most significantly, almost any such enzyme will be more thermostable than the functionally similar enzyme from a lower temperature source. Thermostability is not an isolated property: resistance to heat denaturation imparts stability to a number of other denaturing influences (detergents, organic solvents, etc). These characteristics of hyperthermophilic enzymes are the most likely basis for the development of new biotechnological applications. A limited number of hyperthermophilic enzymes have found application in specialist biotechnological applications; others have visible potential in growing areas of biotechnology. Existing and potential applications are discussed using DNA manipulation enzymes, dehydrogenases, and esterases as examples. PMID- 1445405 TI - Thermoacidophilic archaebacteria: potential applications. PMID- 1445406 TI - Biotechnological potential of methanogens. AB - Methane produced microbiologically is currently used as an energy source, especially by cities and industries, albeit at a level far below its potential; the incentive is currently to save money on disposal costs for waste problems. Anaerobic digestion can be helpful in degrading several halogenated hydrocarbon wastes, and methanogens are partly responsible. Ethane instead of methane may be a future product of interest. Some pure cultures of methanogens may be suitable for production of B-12, or perhaps the speciality biochemical F420, a 5 deazaflavin of interest to both methanogen and streptomyces researchers. Methanogens can cause a variety of problems, including biocorrosion, increased atmospheric methane, and ruminant nutrition loss. Studies of tropical wetlands, including rice paddies and swamps, and the study of a variety of ruminants in the tropics are particularly interesting and appropriate at this time, with respect to methane produced in these ecosystems. In some cases, it may be possible to control methane production by the use of inhibitors or ecological control mechanisms. PMID- 1445407 TI - Where next with the archaebacteria? PMID- 1445408 TI - Bioenergetics and autotrophic carbon metabolism of chemolithotrophic archaebacteria. PMID- 1445409 TI - Biochemistry of methanogenesis. PMID- 1445410 TI - Archaebacterial lipids: structure, biosynthesis and function. AB - The foregoing review of membrane lipids in archaebacteria has revealed a remarkable variety of polar lipids classes, including phospholipids, glycolipids, phosphoglycolipids and sulpholipids, all derived from the one basic core structure, diphytanylglycerol (1) and an equally remarkable set of novel pathways for their biosynthesis. Even with the relatively limited knowledge that we have of the physical properties of these lipids, it is clear that they are well adapted as membrane components to the particular environmental conditions of the three groups of archaebacteria, extreme halophiles, methanogens, and thermoacidophiles. However, much remains to be learned concerning the precise asymmetric arrangement of the lipids in the membrane bilayers or monolayers, the interaction of the lipids with the membrane proteins, and the function of this membrane lipid asymmetry with respect to ion transport, permeability to nutrients, proton transport and conductance, and energy transduction. Perhaps then these unusual lipids will not appear so strange and our knowledge of them will help us to understand the function of the more familiar lipids in the eubacteria and eukaryotes. PMID- 1445411 TI - The enzymology of archaebacterial pathways of central metabolism. AB - From a comparison of the pathways of central metabolism in the archaebacteria, eubacteria and eukaryotes, it is clear that the basic pathways were established before the divergence of the three kingdoms, but that the notable differences may provide important clues to their evolution. From these comparisons, enzymes found in all evolutionary groups have been chosen for detailed structural studies; given the range of extreme phenotypes found within the archaebacteria, these studies will be crucial to our understanding of the structural basis for protein stability and how such features may be engineered into a protein of choice. PMID- 1445412 TI - Progress in developing the genetics of the halobacteria. PMID- 1445413 TI - RNA polymerases and transcription in archaebacteria. PMID- 1445414 TI - Structure, function and evolution of the archaeal ribosome. PMID- 1445415 TI - Chromosome structure and DNA topology in extremely thermophilic archaebacteria. PMID- 1445416 TI - Alternative functional relationships between ELF field exposure and possible health effects: report on an expert workshop. AB - If exposure to 60 Hz fields poses risks to public health, the relationship between exposure and risk may involve something other than the product of field strength and time. Such alternative possible relations, or "effects functions," are of great interest to epidemiologists, engineers, risk analysts, and regulators. A structured survey and workshop were used to explore whether leading researchers in bioelectromagnetics share similar views about alternative possible effects functions. Substantial agreement was found about several effects functions in a few specific contexts such as calcium-ion efflux and cell signalling, and biosynthesis pathways. No significant agreement emerged in many other contexts. No effects function possibilities were ruled out. Further effort of this sort was judged unlikely to yield greater consensus until more complete scientific understanding becomes available. However, a series of structured workshops on research planning and priority setting were judged to hold great potential for useful results. PMID- 1445417 TI - Rats are not aversive when exposed to 60-Hz magnetic fields at 3.03 mT. AB - Thirty-two male rats were tested in two replicates of an experiment to determine whether body currents induced by 60-Hz magnetic fields might lead to avoidance behavior comparable to that which results from exposure to strong 60-Hz electric fields. The test apparatus was a two-compartment Plexiglas shuttlebox enclosed in a sound-attenuating plywood chamber, which in turn was encompassed by two copper bus bars that, when energized, served as a source of 60-Hz magnetic fields. Location of the rat, and traverse activity in the shuttlebox were monitored by nine infra-red photo detectors equally spaced along the length of the apparatus. Rats were divided into 2 groups: 1 group of rats (n = 8 per group per replicate) was sham exposed while rats in the other group (n = 8 per group per replicate) were exposed to a 3.03 mT (30.3 G), 60-Hz magnetic field whenever they traversed to or were located on the side (L or R) predetermined as the exposed side. To control artifact incident to side preference, the side exposed (L or R) was alternated over the exposed rats. Each rat was tested individually in a 1-h session. A 2-factor ANOVA (exposed vs. control, replicate 1 vs. replicate 2) failed to reveal any significant effects due to either factor or to an interaction between factors. These data demonstrate that rats do not avoid exposure to 60-Hz magnetic fields at a flux density of 3.03 mT and further imply that the avoidance by rats of high level 60-Hz electric fields is mediated by something other than the internal body currents induced by the exposure. PMID- 1445418 TI - Relative-risk-estimate bias and loss of power in the Mantel test for trend resulting from the use of magnetic-field point-in-time ("spot") measurements in epidemiological studies based on an ordinal exposure scale. AB - We assessed the merits of various point-in-time ("spot") measurement protocols in case-control studies based on an ordinal exposure scale. After classifying a number of houses on the basis of prolonged monitoring of the ambient, extremely low frequency (ELF) magnetic field, we determined the probability of misclassification for each "spot" measurement protocol. We calculated the effect of this misclassification on the relative risk estimates and on the Mantel test for trend. We found that classification based on a small group of point-in-time measurements allows an adequate estimate of the relative risk, although the statistical significance of the dose-response gradient may be seriously underestimated. However, the use of automated ambient-field monitors, which results in loss of information on spatial variability, can lead to similar consequences. Therefore, manually collected point-in-time measurements remain a viable option for exposure assessment. PMID- 1445419 TI - Increased sensitivity of the non-human primate eye to microwave radiation following ophthalmic drug pretreatment. AB - Previous studies in our laboratory have established that pulsed microwaves at 2.45 GHz and 10 mW/cm2 are associated with production of corneal endothelial lesions and with disruption of the blood-aqueous barrier in the non-human primate eye. In the study reported here we examined ocular damage in monkeys (M. mulatta and M. fascicularis) following topical treatment with one of two ophthalmic drugs (timolol maleate and pilocarpine) that preceded exposure to pulsed microwaves. Anesthetized monkeys were sham exposed or exposed to pulsed, 2.45 GHz microwaves (10 microseconds, 100 pps) at average power densities of 0.2, 1, 5, 10, or 15 mW/cm2 4 h a day for 3 consecutive days (respective SARs were 0.052, 0.26, 1.3, 2.6, and 3.9 W/kg). Immediately before microwave exposure, one or both eyes were treated topically with one drop of 0.5% timolol maleate or of 2% pilocarpine. Following administration of a drug, we observed a significant reduction in the power-density threshold (from 10 to 1 mW/cm2) for induction of corneal endothelial lesions and for increased vascular permeability of the iris. Diagnostic procedures (in vivo specular microscopy and fluorescein iris angiography) were performed following each exposure protocol. In addition, increased vascular permeability was confirmed with horseradish peroxidase tracer techniques. Although we did not measure intraocular temperatures in experimental animals, the results suggest that a mechanism other than significant heating of the eye is involved. Our data indicate that pulsed microwaves at an average SAR of 0.26 W/kg, if administered after pretreatment with ophthalmic drugs, can produce significant ocular effects in the anesthetized primate. PMID- 1445420 TI - Effects of a 30 kV/m, 60 Hz electric field on the social behavior of baboons: a crossover experiment. AB - Using a crossover experimental design, we evaluated our earlier findings that exposure to a 30 kV/m, 60 Hz electric field for 12 hours per day, 7 days per week for 6 weeks produced significant changes in the performance rates of social behaviors among young adult male baboons. In the crossover experiment, the former control group was exposed to a 30 kV/m, 60 Hz electric field for 3 weeks. Only an extremely small, incidental magnetic field was generated by the exposure apparatus. We found that electric-field exposure again produced increases in the performance rates that index Passive Affinity, Tension, and Stereotypy. These findings, combined with results from our other electric-field experiments, indicate that exposure to strong electric fields, in the absence of associated magnetic fields, consistently produces effects that are expressed as increases in rates of performance of social behaviors in young adult male baboons. PMID- 1445421 TI - Uniform magnetic fields and double-wrapped coil systems: improved techniques for the design of bioelectromagnetic experiments. AB - A common mistake in biomagnetic experimentation is the assumption that Helmholtz coils provide uniform magnetic fields; this is true only for a limited volume at their center. Substantial improvements on this design have been made during the past 140 years with systems of three, four, and five coils. Numerical comparisons of the field uniformity generated by these designs are made here, along with a table of construction details and recommendations for their use in experiments in which large volumes of uniform intensity magnetic exposures are needed. Double wrapping, or systems of bifilar windings, can also help control for the non magnetic effects of the electric coils used in many experiments. In this design, each coil is wrapped in parallel with two separate, adjacent strands of copper wire, rather than the single strand used normally. If currents are flowing in antiparallel directions, the magnetic fields generated by each strand will cancel and yield virtually no external magnetic field, whereas parallel currents will yield an external field. Both cases will produce similar non-magnetic effects of ohmic heating, and simple measures can reduce the small vibration and electric field differences. Control experiments can then be designed such that the only major difference between treated and untreated groups is the presence or absence of the magnetic field. Double-wrapped coils also facilitate the use of truly double-blind protocol, as the same apparatus can be used either for experimental or control groups. PMID- 1445422 TI - Small integrating meter for assessing long-term exposure to magnetic fields. AB - A small, lightweight meter has been developed for magnetic-field measurements, particularly those needed for exposure-assessment purposes. This meter, known as the AMEX-3D, continuously measures all three axes of magnetic-flux density and electronically combines the data into a single estimate of cumulative exposure to the root-mean-square (rms) resultant flux density. The AMEX-3D weighs about 120 g, measures 2.7 cm x 5.1 cm x 10.2 cm, and is battery powered. Two panel-mounted jacks are provided for measuring battery voltage and for reading cumulative exposure data from the unit. The instrument has, within 3 dB, a flat response to magnetic flux densities at all frequencies in its 30-1,000 Hz bandwidth. A detailed analysis of error sources in the AMEX-3D leads to an estimate of +/- 20% as the accuracy of the instrument over its dynamic range, which extends from 0.02 to 15 microT. The AMEX-3D was tested in the field by asking electric-utility distribution linemen to wear AMEX-3D and EMDEX meters simultaneously while working. Agreement between the two measures of exposure was excellent. PMID- 1445423 TI - Statistical review of the henhouse experiments: the effects of a pulsed magnetic field on chick embryos. AB - This paper analyzes data from a study conducted by the United States Office of Naval Research on the effects of pulsed magnetic fields on chick embryos. The experiment involved incubation of eggs under carefully controlled conditions in six different laboratories. The original analysis included inappropriate statistical methodology for analyzing the experimental results. Since the conclusions from this study rest so heavily on the results of statistical analyses, choosing the proper methodology is imperative. The major aim of this paper then is to introduce more appropriate analytic tools and illustrate their use in the present context. Qualitatively our results agree with those of the original analysis; our findings about interactions between effects, however, makes interpretation of these effects more subtle. We apply linear logistic modeling to counts of damaged embryos, using as covariates factors corresponding to exposure, laboratory, incubator, run, and measurements of background radiation. This facilitates estimation of the size of the effects. The effects of laboratory, incubator, and run are explored both as fixed and random effects. We find statistically significant exposure and laboratory effects, in accordance with the original study. However, we also find that the inter-laboratory variation in exposure effect is at least as large as the exposure effect itself. The presence of such effects fundamentally alters the interpretation of the fitted model, as is graphically presented. PMID- 1445424 TI - Whole-body microwave dosimetry based on a single, gradient-layer calorimeter. AB - A simple, cost-effective, and accurate technique to measure the whole-body averaged specific absorption rate (SAR) in Sprague-Dawley rat carcasses by a single-gradient-layer calorimeter is described. The results of SAR determinations showed a highly linear relation between the average power density of the incident field (1.25 GHz) and the normalized heat loading of the carcasses. PMID- 1445425 TI - Currents induced in a model of a rat exposed to EMP in a parallel-plate line: calculations and experimental results. PMID- 1445426 TI - [Site-directed chemical restriction of a single-stranded DNA fragment by an alkylating derivative of the tetranucleotide d(pApGpCpA) in the presence of tetranucleotide effectors]. AB - Alkylation of a single-stranded DNA 302-mer by a 5'-O-phosphoryl-[4-(N-2 chloroethyl-N-methylamino)benzyl]amide derivative of the tetradeoxyribonucleotide d(pApGpCpA) in the presence of 3',5'-di-N-(2-hydroxyethyl) phenazinium derivatives of tetranucleotides as effectors led to specific chemical cleavage of the target at the guanosine residues of the sites ... pTpGppT. The reagent can be selectively addressed to one of three alkylation sites with the aid of a pair of tetranucleotide effectors flanking the chemically reactive tetranucleotide in the complex with the target DNA. The yield of the cleavage depends on the concentration of both the reagent and effectors, and can be enhanced, if a chain of two or more effectors from each side of the reagent is used. In this case, 3',5'-di-Phn-tetranucleotide effectors are to immediately flank the reagent. PMID- 1445427 TI - [Study of the spatial structure of the duplex (Phn NH(CH2)NH)pd(CCAAACA).pd(TGTTTGGC) with covalently bound 10-(2 hydroxyethyl)phenazine by in aqueous solution by 2D-(1)H-NMR and by limited molecular mechanics]. AB - Detailed investigation of the spatial structure of duplex (Phn-NH(CH2)2NH) x pd(CCAAACA).pd(TGTTTGGC) having a covalently linked N-(2-hydroxyethyl)-phenazine in aqueous solution was continued by means of one- and two-dimensional 1H-NMR spectroscopy. Distances between the protons of the oligonucleotides as well as distances between the phenazinium and the nearest nucleotide groups protons were determined from the series of one-dimensional NOE experiments. The effective correlation time tau c determined for some proton pairs shows the phenazinium fragment to have greater internal motion than the heterocyclic bases. The deoxyribose protons coupling constants show the sugars to be in 2'-endo conformation. The restrained molecular mechanics have yielded a possible structure of duplex in the aqueous solution fitting the experimental set of interproton distances. PMID- 1445428 TI - [Directed mutagenesis of genes of some plant proteins]. AB - Mutagenesis of two previously cloned plant genes, maize storage protein cZ22B1 gene and barley Photosystem II protein D1 gene (psbA), was carried out. To improve the nutritional quality of zein, the DNA region corresponding to the protein sixth alpha-helix rod was substituted by a synthetic segment bearing three codon changes for Lys. Additional stabilization of this helix was achieved by three more codon changes for Glu. By means of oligonucleotide directed mutagenesis five different copies of psbA gene were obtained, bearing single codon change of Ser264 (wild type) for Gly, Ala, Cys, Asn, and Thr, respectively. These constructs can be used for studying functional topography of protein D1 and core region. PMID- 1445429 TI - [Physico-chemical and immunochemical characteristics of molecular forms of carcinoembryonic antigen (CEA) not bound with concanavalin A]. AB - A molecular form of CEA non-binding Con A (CEAnC) was isolated from colon adenocarcinoma metastases in liver as a fraction of CEA having no affinity to Con A-Sepharose. CEAnC was shown to be immunochemically identical to CEA, but to differ substantially with regard to the amino acid and sugar composition, and structure of the sugar moiety, possibly containing non only N-, but also O glycosyl carbohydrate chains. The antigens studied were also found to possess different spatial structures. The differences between CEA and CEAnC suggest CEAnC to be a new molecular form of CEA. PMID- 1445430 TI - [Protection of naturally susceptible animals against foot-and-mouth disease with a peptide, synthesized on a lysine matrix]. AB - A peptide VP1-(142-158)-MAP (Multiple antigen peptide system) consisting of two parts: a lysine matrix made up of three levels of lysine residues coupled with each other and amino acid sequence 142-158 of VP1 of FMD virus strain A(22)550- has been synthesized. Guinea-pigs inoculated with 20 mkg of the peptide incorporated with Freund's complete adjuvant were protected against challenge with 500 ID50 of homologous FMD virus. Sheep were immunized with a single inoculation of the peptide in a dose of 1.0 mg. Cattle inoculated twice with 1.5 mg of the peptide with incomplete adjuvant on the basis of synthetic oil developed high virus-specific antibody titres both after the first (5.3-7.6 log2 ND50/0.1 ml) and the second inoculation (10.2-11.0 log2 ND50/0.1 ml). The peptide immunized animals were resistant to challenge with homologous virulent virus in a dose of 10(4) ID50. The immunogenic and protective capacities of the peptide VP1 (142-158)-MAP were shown to be greater as compared with those of its linear analogue-peptide VP1-(141-160). PMID- 1445431 TI - [Transformation products of vitamin E and its analog--chroman C1 in an oxidizing ethyl linoleate medium]. AB - Spirodimers, dimers, quinones of alpha-tocopherol and chroman C1 have been synthesized by the alpha-tocopherol and chroman Ci oxidation with K3[Fe(CN)6] and FeCl3. Products of the oxidative transformation of alpha-tocopherol and chroman Ci, viz. dimers, quinones and trimers, in the media of ethyllinoleate and nonane have been identified by HPLC, TLC, UV, IR and 1H NMR spectroscopy. The mechanism of the transformation and modifying activity of chromans under various oxidation conditions are discussed with regards to the experimental data. PMID- 1445432 TI - [Molecular and crystalline structure of 3'-methylamino-2',3' dideoxyribosylthymine--a potential inhibitor of HIV]. AB - The structure of 3'-methylamino-2',3'-dideoxyribosylthymine [ddT(3'NHMe)] was determined by X-ray analysis. The space group is P2(1)2(1)2(1). Cell dimensions are: a 5.132(1), b 13.718(1), c 16.947(2) A, V 1193.2 A3, Z 4. The structure was solved by directed methods and refined by the full-matrix least square method to R 4.8%. The molecule of ddT(3'NHMe) has anti-conformation with respect to the glycosidic bond (chi (O4'-C1'-N1-C2) = -106.7 degrees), C3'-endo-C4'-exo puckering of the sugar moiety (P -28.8 degrees, psi m -31.5 degrees) and gauche gauche conformation about exocyclic C4'-C5' bond (psi(C3'-C4'-C5'-O5') 45.8 degrees). The structure of ddT(3'NHMe) was compared with those of 3'-amino-3' deoxythymidine, 3'-azido-3'-deoxythymidine and natural thymidine. PMID- 1445433 TI - [Achievements and prospects of the directed search for antiviral agents in the nucleoside series and their derivatives]. AB - Recent advances of antiviral drug design among nucleosides and their derivatives have been summarized. The first chapter deals with the history of nucleic acids components and further developments in this area. Next part discusses the mechanism of action of biologically active nucleosides: 2',3'-dideoxynucleosides, acyclic analogues, phosphonate derivatives and nucleoside antibiotics. The third chapter describes planning of complicated synthesis of nucleoside analogues from branched-chain sugars and stereo-specific formation of glycosidic bond upon synthesis of ribonucleoside and 2'-deoxyribonucleoside. The last part outlines further perspectives, i. e. preparation of antiviral compounds and use of nucleoside analogues in oligonucleotide synthesis. PMID- 1445434 TI - [The mechanism of anticholinesterase action of acetylene organophosphorus inhibitors]. AB - Introduction of the triple bond in the leaving group of the organophosphorus inhibitor molecule gives a sharp raise of the inhibitor activity but does not change principal characteristics of the cholinesterase inhibition mechanism. The reactivation experiments suggest that inactivation of cholinesterases by these compounds occurs due to phosphorylating of the serine hydroxyl by the corresponding phosphoric acid. A close similarity was shown between acetylenic and saturated organophosphorus inhibitors in altering ka upon change of pH and tetraalkylammonium ions action. It is demonstrated that S-alkynyl esters of thioacetic acid are slowly hydrolyzed by acetylcholinesterase and cholinesterase without irreversible inhibition of the enzymes. PMID- 1445435 TI - [Pepsin in the enzymatic synthesis of esters and n-nitroanilide peptides]. AB - Pepsin was shown to catalyze synthesis of esters or p-nitroanilides tri-, tetra-, penta- and hexapeptides of general formula Z-X-Y-B, where X = Ala-Phe, Phe-Met, Ala-Ala-Glu, Ala-Ala-Phe, Ala-Ala-Leu, Ala-Ala-Trp, Ala-Ala-Met. Y = Ala, Leu, Val, Phe, Arg, Ala-Ala, Gly-Gly, Leu-Ala-Ala, Phe-Ala-Ala. B = OMe, pNA. The reactions were carried out in dimethylformamide-water solutions at pH 4.6 by equimolar ratio of amino- and carboxyl components (with the exception of Arg-pNA taken in 2-fold excess). The amount of pepsin in the reaction approached 1:1700 enzyme: substrate molar ratio although it might be improved--up to 1:3.10(5) for relatively long peptides. PMID- 1445437 TI - [Preparation of 5-(125)iodine-2'-deoxyuridine triphosphate and incorporation of the labeled nucleotide into DNA by polymerase chain reaction]. AB - Radioiodine was substituted into deoxyuridine triphosphate by radioiodination of 5-mercuri-2'-deoxyuridine triphosphate. The purified 125I-nucleotide was incorporated into DNA in reactions by the protocol of the polymerase chain reaction. The incorporation of the radioactive nucleotide required added thymidine triphosphate for the synthesis of full length molecules during the one minute elongation period. The iodine substituent in the DNA remained covalently bound during both heat and alkaline denaturation. PMID- 1445436 TI - [Synthesis and expression in Escherichia coli of the gene for the albumin-binding domain of Streptococcus protein G]. AB - The chemical-enzymatic synthesis of a gene coding for A2B2 repeats of the albumin binding domain of streptococcal protein G has been accomplished. The codon usage of the natural gene has been modified to adapt an artificial sequence for the efficient translation in E. coli. The gene (238 b.p.) was cloned in the polylinker plasmid pUCL1 and then fused in frame to the 3'-terminus of the gene for the IgG-binding domain of staphylococcal protein A, which was earlier cloned in the expression plasmid pUCL2. A fused polypeptide composed of the E and B domains of protein A and A2B2 repeats of protein G was produced in E. coli cells under the lac promoter control. The resulted product was isolated by affinity chromatography on IgG-sepharose and (or) albumin-sepharose. PMID- 1445438 TI - [Change in the cleavage site of synthetic substrates of SsoII restriction endonucleases upon introduction of non-nucleotide inserts in the recognition segment]. AB - The cleavage of synthetic DNA duplexes containing 1,3-propanediol, 1,2-dideoxy-D ribofuranose or 9-[1'-hydroxy-2'-(hydroxymethyl)ethoxy]methylguanine (glG) residues instead of one of dG residues or one of the nucleosides of the central base pair of the recognition site by SsoII restriction endonuclease (decreases CCNGG) has been studied. It is found that the non-nucleotide insertions (except for glG) result in a change of the SsoII cleavage site and an increase of the efficiency of the cleavage. The novel noncanonical cleavage occurs at the phosphodiester bond adjoining the non-nucleotide insert from the 5'-end. PMID- 1445439 TI - Informed consent and the prescription of nonsteroidal antiinflammatory drugs. AB - OBJECTIVE: To examine disclosure of side effects of nonsteroidal antiinflammatory drugs (NSAIDs) and to identify patient- and physician-specific factors associated with greater disclosure. METHODS: Forty-six encounters between rheumatologists and new adult outpatients who were prescribed an NSAID they had not been taking prior to the visit were audiotaped. Reviewers coded the NSAID prescribed, specific side effects mentioned, demographic features of patients and physicians, and patient clinical characteristics. Neither patients nor physicians were aware that side effect disclosure was being studied. RESULTS: A mean of 1.7 side effects was mentioned per encounter. Epigastric discomfort was mentioned in 72% of encounters, while other side effects, including hepatic, renal, hematologic, or central nervous system effects, were mentioned in < or = 15% of encounters. Three factors were identified as independent predictors of less disclosure of side effects: senior clinician (versus less experienced), patient not taking another NSAID immediately prior to the visit, and patient age < 40. Increased disclosure by less experienced clinicians occurred exclusively with patients who were taking another NSAID prior to the visit. CONCLUSION: Disclosure of side effects other than epigastric discomfort to patients who are prescribed a new NSAID is limited. Patients not taking NSAIDs previously, who presumably have the most to gain from such discussions, are told the least. These results have implications with regard to doctor-patient decision-making and malpractice litigation in the outpatient setting. PMID- 1445440 TI - Informed consent. PMID- 1445441 TI - Psychological well-being among people with recently diagnosed rheumatoid arthritis. Do self-perceptions of abilities make a difference? AB - OBJECTIVE: Satisfaction with abilities and perceived importance of abilities are 2 factors involved in the process of self-evaluation. We examined the role that these factors play in adjustment to rheumatoid arthritis (RA). METHODS: Data were collected, via telephone interview and mailed questionnaire, from 234 individuals with recently diagnosed RA. Disease severity information was obtained from participants' physicians. RESULTS: Consistent with study hypotheses, satisfaction was associated with psychological well-being only among those who viewed as very important the abilities being evaluated. CONCLUSION: These findings increase understanding of the conditions under which low levels of satisfaction are likely to be associated with psychological distress. PMID- 1445442 TI - Coping with arthritis. Current status and critique. AB - Our understanding of the complex role of coping in the psychological adjustment to arthritis has improved over the past decade. Studies have consistently demonstrated a relationship between certain coping strategies and psychological outcomes. However, unresolved problems in the methodology and theory concerning these studies cloud the picture, limiting the conclusions that can be drawn. There are general problems with the ways in which coping has been conceptualized and measured by researchers evaluating stress and coping, and there are problems more specific to the ways coping concepts and measures have been used to study patients with arthritis. A complete understanding of the relationship between coping and mental health in this population would have important theoretical and clinical implications. Such studies would serve as a model for investigations of stress and coping in patients with other illnesses, and would point to effective psychosocial interventions for improving the quality of life for this population. PMID- 1445443 TI - Defective hypothalamic response to immune and inflammatory stimuli in patients with rheumatoid arthritis. AB - OBJECTIVE: To determine the integrity of the hypothalamic-pituitary-adrenal (HPA) axis responses to immune/inflammatory stimuli in patients with rheumatoid arthritis (RA). METHODS: Diurnal secretion of cortisol and the cytokine and cortisol responses to surgery were studied in subjects with active RA, in subjects with chronic osteomyelitis (OM), and in subjects with noninflammatory arthritis, who served as controls. RESULTS: Patients with RA had a defective HPA response, as evidenced by a diurnal cortisol rhythm of secretion which was at the lower limit of normal in contrast to those with OM, and a failure to increase cortisol secretion following surgery, despite high levels of interleukin-1 beta (IL-1 beta) and IL-6. The corticotropin-releasing hormone stimulation test in the RA patients showed normal results, thus suggesting a hypothalamic defect, but normal pituitary and adrenal function. CONCLUSION: These findings suggest that RA patients have an abnormality of the HPA axis response to immune/inflammatory stimuli which may reside in the hypothalamus. This hypothalamic abnormality may be an additional, and hitherto unrecognized, factor in the pathogenesis of RA. PMID- 1445444 TI - Scientific workshop on the biology and pathology of acquired connective tissue diseases. PMID- 1445445 TI - Regulation of synovial cell growth. Coexpression of transforming growth factor beta and basic fibroblast growth factor by cultured synovial cells. AB - OBJECTIVE: To demonstrate expression of transforming growth factor beta (TGF beta) and basic fibroblast growth factor (bFGF) by cultured rheumatoid arthritis (RA) synovial cells and to investigate their role as synovial cell mitogens. METHODS: Polypeptide growth factors were detected and identified by immunocytochemical staining and Western blot analysis. Messenger RNA (mRNA) transcripts encoding TGF beta and bFGF were identified by polymerase chain reaction analysis. The influence of neutralizing growth factor monoclonal antibodies (MAb) on RA synovial cell growth was investigated. TGF beta bioactivity was determined by Mv1Lu assay. RESULTS: Lysates of RA, as compared with normal, synovial cells contained greater amounts of TGF beta and bFGF. Western blot analysis identified a single TGF beta band (MW approximately 25 kd) in each of the cell lysates examined. Western blot analysis using MAb DE6 identified a doublet of bFGF bands (MW approximately 18.0 kd) in normal synovial cell lysates and 4 bFGF bands (MW approximately 18.0, 22.0, 22.6, and 25.2 kd) in RA synovial cell lysates. RA and normal synovial cells expressed mRNA transcripts encoding TGF beta 1 but not TGF beta 2, and FGF-2 (basic FGF). Additional mRNA transcripts encoding FGF-5 and FGF-7 were expressed by RA, but not normal, synovial cells in culture. In contrast to MAb 1D11.16, which caused a dose dependent decrease in RA synovial cell growth, MAb DG2 (up to 100 micrograms/ml) had no effect on cell growth. CONCLUSION: RA and normal synovial cells cultured in serum-free medium express TGF beta 1 and native bFGF. However, only RA synovial cells in culture express higher molecular weight isoforms of bFGF. TGF beta 1 appears to regulate synovial cell growth in vitro through an external autocrine loop. Despite expression of high-affinity bFGF receptors on cultured synovial cells, the mechanisms by which bFGF modulates synovial cell growth are unknown. PMID- 1445446 TI - Quantitation of chondroitin 4-sulfate and chondroitin 6-sulfate in pathologic joint fluid. AB - OBJECTIVE: To investigate the correlation between joint disease and the composition of chondroitin sulfate in the joint fluid, unsaturated disaccharide isomers of chondroitin 4-sulfate (delta di-4S) and chondroitin 6-sulfate (delta di-6S) were measured in joint fluids obtained from patients with osteoarthritis (OA), rheumatoid arthritis (RA), or traumatic arthritis (TA). METHODS: These pathologic joint fluids were digested with chondroitinase ABC, and the delta di 4S and delta di-6S produced were determined by high performance liquid chromatography combined with fluorometry. RESULTS: Total content of delta di-4S plus delta di-6S was 71.8 +/- 30.0 nmoles/ml (mean +/- SD) in OA, 55.4 +/- 29.3 nmoles/ml in RA, and 211 +/- 149 nmoles/ml in TA joint fluids. The ratio of delta di-6S to delta di-4S was 3.81 +/- 0.992 in OA, 1.13 +/- 0.527 in RA, and 5.75 +/- 2.46 in TA joint fluids. Differences between groups were statistically significant. CONCLUSION: These results strongly suggest that the levels of chondroitin sulfate isomers and the delta di-6S: delta di-4S ratio in joint fluid reflect the proteoglycan metabolism of joint tissues, particularly of articular cartilage; hence, they could be used to diagnose joint diseases and to predict articular cartilage destruction from such joint diseases. PMID- 1445447 TI - Calcium-dependent cysteine proteinase (calpain) in human arthritic synovial joints. AB - OBJECTIVE: To study the roles of calpains in the synovial joint in rheumatoid arthritis (RA) and osteoarthritis (OA) and to verify the hypothesis that calpains present in the synovial fluid come from the synovium. METHODS: We performed immunohistochemical, biochemical, and immunoblotting analyses for calpains in synovial tissues, synovial cell cultures, and synovial fluids. RESULTS: Immunohistochemical staining of RA synovium demonstrated specific cytoplasmic staining of cells in the synovial lining layer, storomal fibroblasts, and endothelial cells. OA synovium showed almost the same intensity and distribution of calpain staining. DEAE-cellulose chromatography of RA and OA synovial extracts and synovial fluids showed a peak of caseinolytic activity attributable to calpain, as well as an inhibitory peak of calpastatin, a specific inhibitor protein of calpains. Immunoblotting using the anticalpain antibody from the calpain peak of RA and OA synovium and synovial fluid showed identity with the heavy subunit of calpain (80 kd). Similarly, calpain existed in the same form (80 kd) in conditioned media (supernatant) obtained from synovial cell cultures, as well as in the synoviocytes. The total specific activity of the 2 calpains in the synovial fluid of RA patients was higher than that of calpastatin. CONCLUSION: The findings suggest that the extracellular appearance of calpains could be due to the secretion of these proteins from the synovial cells and that calpains may play a role in cartilage damage of RA and OA that occurs in synovial joints. PMID- 1445448 TI - Efficacy and safety of 10-deazaaminopterin in the treatment of rheumatoid arthritis. A one-year continuation, double-blind study. AB - OBJECTIVE: To determine the long-term safety and efficacy of 10-deazaaminopterin (10-DAM) in the treatment of rheumatoid arthritis (RA). METHODS: A 1-year continuation of an initial 15-week randomized, double-blind clinical trial of 10 DAM and methotrexate (MTX). RESULTS: 10-DAM (n = 10) and MTX (n = 8) had comparable safety and efficacy profiles. One 10-DAM-treated and 2 MTX-treated patients experienced transient side effects; 1 MTX-treated patient experienced recurrent nausea and discontinued MTX. CONCLUSION: 10-DAM appears to be as beneficial and as safe as MTX for the treatment of RA. PMID- 1445449 TI - The treatment of Wegener's granulomatosis with glucocorticoids and methotrexate. AB - OBJECTIVE: To identify alternatives to daily low-dose cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG). METHODS: An open-label pilot study of weekly low-dose methotrexate (MTX) plus glucocorticoids (GC) for treatment of patients with WG was performed. Twenty-nine patients who did not have immediately life-threatening disease were included. Outcome was determined by clinical characteristics, pathologic findings, course of illness, laboratory and radiographic findings, and successful withdrawal of GC therapy. RESULTS: Weekly administration of MTX (at a mean stable dosage of 20 mg) and GC resulted in marked improvement in 76% of the 29 patients. Remission was achieved in 69% of the patients, 7% improved but had intermittent smoldering disease that precluded total withdrawal of GC, and 17% had progressive disease within 2-6 months of starting the study treatment. Two patients who initially achieved remission later had relapses after GC was discontinued. Of those who remain in remission (mean followup time 14.5 months), 72% have not required GC for a mean period of 10 months. CONCLUSION: Although standard therapy for WG (daily CYC and GC) has dramatically improved outcome in this often-fatal disease, treatment morbidity has led to attempts to identify effective interventions that have less toxicity. Weekly low-dose MTX was shown in this study to be a feasible alternative to CYC in patients whose illness was not immediately life-threatening or in whom prior CYC treatment was ineffective or produced serious toxicity. Although these results are preliminary, they are encouraging and justify further studies in which MTX, CYC, and other alternative therapeutic approaches are compared concurrently. PMID- 1445450 TI - Quantitative electroencephalography. A new approach to the diagnosis of cerebral dysfunction in systemic lupus erythematosus. AB - OBJECTIVE: Neuropsychiatric manifestations are common in patients with systemic lupus erythematosus (SLE), but accurate diagnosis is often difficult. We conducted a prospective study to determine the utility of neurometric quantitative electroencephalography (QEEG) as an indicator of cerebral dysfunction in SLE patients. METHODS: Fifty-two SLE patients were divided into 4 groups based on the results of neuropsychiatric evaluations. These included patients with objective evidence of neuropsychiatric SLE (NPSLE), patients with neuropsychiatric symptoms, patients with no evidence of NPSLE, and patients with a prior history of NPSLE: All QEEG findings were compared with data in an age regressed normative database and with findings in an independent sample of normal subjects. RESULTS: QEEG sensitivity was 87%, and specificity was 75%. QEEG results were abnormal in 74% of the SLE patients with neuropsychiatric symptoms and in 28% of the patients with no evidence of active NPSLE: QEEG profiles varied as a function of the severity and type of neuropsychiatric manifestation present. Within this patient population, QEEG was more sensitive than magnetic resonance imaging, computed tomography scanning, or conventional EEG. CONCLUSION: Neurometric QEEG may be a sensitive indicator of cerebral dysfunction in patients with NPSLE and can differentiate patients with diverse neuropsychiatric manifestations. When combined with a careful clinical history and evaluation, QEEG provides information that may be useful for the early detection of NPSLE and for serial evaluation of disease activity and treatment efficacy. PMID- 1445451 TI - The spectrum of pericardial tamponade in systemic lupus erythematosus. Report of ten patients. AB - OBJECTIVE: To describe the range of clinical manifestations and the outcome of pericardial tamponade in patients with systemic lupus erythematosus (SLE). METHODS: Patients with pericarditis and with pericardial tamponade were identified from our computerized database of 395 SLE patients. Medical records were reviewed to establish activity of SLE at the time of tamponade, as well as clinical and laboratory features, treatment, and outcome of the tamponade. RESULTS: Pericarditis occurred in 75 patients (19%), with 11 episodes of tamponade in 10 of them (13%; 2.5% of entire series). Tamponade was the initial manifestation of SLE in 4 patients. Seven episodes occurred during active lupus, with nephritis present in 6. Signs of venous congestion, including ascites and facial or peripheral edema, were the most common manifestation of tamponade. Pericardial fluid was exudative, and pericardial tissue demonstrated a range of findings including fibrinous and fibrotic changes, acute and chronic inflammatory infiltrates, and vascular proliferation. Tamponade was fatal in 1 patient, and 2 patients each had recurrent effusions and pericardial thickening. CONCLUSION: Pericardial tamponade may occur at any point in the course of SLE, and should be considered in patients with unexplained signs of venous congestion. The differential diagnosis includes active SLE, uremia, and infection. Treatment with high-dose steroids and either pericardiocentesis or placement of a pericardial window is indicated, but recurrent effusions or pericardial thickening may develop. PMID- 1445452 TI - The effect of cyclosporin A on early and late stages of experimental lupus. AB - OBJECTIVE: To investigate the effect of cyclosporin A (CSA) on the development of lupus in an experimental model. METHODS: Lupus was induced in naive mice following injection of a human anti-double-stranded DNA (anti-dsDNA) monoclonal antibody carrying the 16/6 idiotype (Id). CSA was injected into the mice at an early stage of the disease (2 months after immunization) and at a late stage (4 months after immunization). RESULTS: CSA was found to have a suppressive effect on autoantibody production, as well as on the appearance of other disease manifestations, in the mice with lupus. The effects of the drug were more prominent when the mice were treated at an early stage. This was reflected by a dramatic decrease, to normal levels, in autoantibodies to dsDNA, histones, cardiolipin, Sm, RNP, SS-A/Ro, SS-B/La, and anti-DNA 16/6 Id. Similar effects on the erythrocyte sedimentation rate, white blood cell count, and urinary protein levels were noted. These data were supported by electron microscopy analysis showing a lack of immunoglobulin deposition in the kidneys of mice in which treatment was started early. CONCLUSION: This study demonstrates that, similar to findings in other autoimmune conditions (e.g., insulin-dependent diabetes mellitus), administration of CSA at an early stage in systemic lupus erythematosus may be more beneficial than if the drug is given at a later stage. PMID- 1445453 TI - Cardiac involvement in systemic sclerosis. AB - OBJECTIVE: To assess the incidence and extent of cardiac involvement in systemic sclerosis (SSc) patients with no apparent cardiac symptoms. METHODS: Surface electrocardiography, ambulatory electrocardiography, radionuclide ventriculography, myocardial scintigraphy, and echocardiography were performed in 18 patients. RESULTS: These studies demonstrated ventricular tachycardia in 1 patient, nonsustained ventricular tachycardia in 5, supraventricular tachycardia in 6, decreased left ventricular ejection fraction in 2, decreased right ventricular ejection fraction in 8, and stress-induced reversible myocardial perfusion abnormalities in 6. CONCLUSION: These observations demonstrate a high rate of cardiac abnormalities in SSc patients without cardiac symptoms. PMID- 1445454 TI - Restricted junctional usage of T cell receptor V beta 2 and V beta 13 genes, which are overrepresented on infiltrating T cells in the lips of patients with Sjogren's syndrome. AB - OBJECTIVE: To analyze the clonality of T cell receptor (TCR) V beta 2- and V beta 13-positive T cells, which are predominantly expressed in the lips of patients with Sjogren's syndrome (SS). METHODS: The junctional sequences of complementary DNA clones encoding TCR V beta 2 and V beta 13 genes were determined by the polymerase chain reaction. Forty-one V beta 2 and 45 V beta 13 clones established from the lips of 3 SS patients were sequenced. RESULTS: The V beta 2/J beta 2.3 pair was enriched in 2 of the 3 patients (44% and 46% of the clones, respectively), and the V beta 13/J beta 2.1 sequence was dominant in 2 of the 3 (23% and 45%). These pairs were not used preferentially in peripheral blood lymphocytes from the same patients. CONCLUSION: Infiltrating V beta 2- and V beta 13-positive T cells from the lips of all 3 patients with SS were polyclonal, but the junctional usage of cells from 2 lip samples was restricted, compared with cells from peripheral blood. This suggests that not all expanded cells from the lips of SS patients are stimulated by superantigens. PMID- 1445455 TI - Serum anti-SS-B/La and IgA rheumatoid factor are markers of salivary gland disease activity in primary Sjogren's syndrome. AB - OBJECTIVE: To identify serologic markers of salivary gland disease activity in 43 patients with primary Sjogren's syndrome. METHODS: Comparison of salivary gland biopsies (focus scores) and flow rates with serum concentrations of IgA and IgM rheumatoid factor (RF), total serum IgG, serum anti-SS-B/La antibodies, and the erythrocyte sedimentation rate. RESULTS: Serum anti-SS-B/La antibody levels correlated with focus scores (rs = 0.477, P < 0.0025). Serum IgA-RF concentrations correlated inversely with stimulated parotid gland salivary flow rates (rs = -0.394, P < 0.01). CONCLUSION: Measuring serum levels of anti-SS-B/La and IgA-RF would be useful when monitoring salivary responses in therapeutic trials, especially in patients with minimal salivary function. PMID- 1445456 TI - Antineutrophil cytoplasmic autoantibody-associated vasculitis presenting as Sjogren's syndrome. AB - A 63-year-old woman, in whom a diagnosis of Sjogren's syndrome was initially made, proved to have systemic vasculitis with salivary gland involvement and necrotizing and crescentic glomerulonephritis. Antineutrophil cytoplasmic autoantibodies (ANCA) against myeloperoxidase were positive. ANCA-associated vasculitis should be considered in the differential diagnosis of Sjogren's syndrome. A positive finding on immunoassay for ANCA against myeloperoxidase or proteinase 3 may help establish the diagnosis. PMID- 1445457 TI - Heavy and light chain composition of serum IgA and IgA rheumatoid factor in Henoch-Schonlein purpura. AB - OBJECTIVE: To characterize the heavy and light chain composition of serum IgA and IgA rheumatoid factor (RF) in 34 children with Henoch-Schonlein purpura (HSP). METHODS: Serum IgA and IgA subclass concentrations were measured by radial immunodiffusion. IgA-RF and the light chain composition of serum IgA and IgA-RF were determined by enzyme immunoassay. RESULTS: Serum IgA and IgA1 concentrations were higher in HSP patients than controls (P = 0.0001), but there was no difference in IgA2 concentrations between the two groups. IgA-RF was present in 19 of 34 HSP patients; it was composed predominantly of IgA1. The kappa:lambda ratio of serum IgA was virtually identical in patients and controls, but the kappa:lambda ratio of IgA-RF was significantly higher than that of the serum IgA from the 19 IgA-RF seropositive patients (P = 0.0003). CONCLUSION: Serum IgA1 is preferentially increased in children with HSP, but the light chain composition of IgA is not different from that in controls. IgA-RF is common in HSP; it is composed predominantly of IgA1 and it is enriched in kappa light chains. PMID- 1445458 TI - Suppression of renal disease and arthritis, and prolongation of survival in MRL lpr mice treated with an extract of Tripterygium wilfordii Hook f. AB - OBJECTIVE: Treatment of MRL-lpr/lpr mice with Tripterygium wilfordii Hook f (TWHf) to evaluate its effects on mortality, renal disease, and arthritis. METHODS: Mice were fed water (group A, control), TWHf (group B), or first water and then TWHf (group C) from age 7 weeks until age 21 weeks. RESULTS: Arthritis and glomerulonephritis were decreased in groups B and C mice, and survival was increased in group B mice. CONCLUSION: TWHf decreases the mortality rate, and severity of glomerulonephritis and arthritis in MRL-lpr/lpr mice. PMID- 1445460 TI - Radiologic vignette. Primary Madelung's deformity. PMID- 1445459 TI - Premature death with bladder outlet obstruction and hyperprolactinemia in New Zealand black X New Zealand white mice treated with ethinyl estradiol and 17 beta estradiol. AB - OBJECTIVE: To determine causes of death, estrogen toxicity, and hyperprolactinemia in a murine model of systemic lupus erythematosus (SLE). METHODS: Female New Zealand Black x New Zealand White (NZB x NZW) mice were implanted with ethinyl estradiol, 17 beta-estradiol, or empty capsules (controls). RESULTS: Estrogen-treated mice developed striking hyperprolactinemia and died prematurely with genitourinary complications. CONCLUSION: Implanted estrogens, including 17 beta-estradiol in a dose reported previously to stimulate SLE, contribute to premature death in NZB x NZW mice, through toxic effects. Estrogen therapy increases the level of prolactin, an immunostimulatory hormone. PMID- 1445461 TI - Management of asymptomatic Borrelia burgdorferi infection. PMID- 1445462 TI - Specific binding of lipocortin-1 (annexin I) to monocytes and neutrophils is decreased in rheumatoid arthritis. PMID- 1445463 TI - Genotypes of polymorphic arylamine N-acetyltransferase in systemic lupus erythematosus. PMID- 1445464 TI - Tophaceous gout as a fungating mass. PMID- 1445465 TI - T cell activation through CD3 molecules in patients with systemic lupus erythematosus. PMID- 1445466 TI - Interleukin-6 in scleroderma: comment on the article by Needleman et al. PMID- 1445467 TI - Sjogren's syndrome and assays for retroviral proteins: reply. PMID- 1445468 TI - Sjogren's syndrome and retroviral protein reactivity: reply. PMID- 1445469 TI - Auranofin, methotrexate, but no placebo: comment on the article by Williams et al. PMID- 1445470 TI - Are there subsets of autoantibodies to nuclear lamins? PMID- 1445471 TI - In vitro studies on the influence of L-ascorbic acid 2-[3,4-dihydro- 2,5,7,8 tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6yl-hy drogen phosphate] potassium salt on lipid peroxidation and phospholipase A2 activity. AB - The effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2- (4,8,12 trimethyltridecyl)-2H-1-benzopyran-6yl-hydrogen phosphate] potassium salt (EPC K1, CAS 127061-56-7), a new compound for ischemia-reperfusion injuries, on lipid peroxidation and phospholipase A2 activity were studied in vitro using rat brain homogenates and human plasma. EPC-K1 inhibited phospholipase A2 activity in human plasma in a concentration-dependent manner (IC50 = 7.3 x 10(-4) mol/l), whereas a mixture of alpha-tocopherol and ascorbic acid did not exhibit this effect. In rat brain homogenates, EPC-K1 also inhibited lipid peroxidation in a concentration dependent manner (IC50 = 2.3 x 10(-6) mol/l). alpha-Tocopherol was less active than EPC-K1. These properties of EPC-K1 suggest that EPC-K1 may prove useful in the treatment of ischemia-reperfusion injuries. PMID- 1445472 TI - Enhancement of nerve fibre regeneration by nucleotides after peripheral nerve crush damage. Electrophysiologic and morphometric investigations. AB - The effect of nucleotide administration on the regeneration of myelinated nerve fibres following crush injury to the sciatic nerve of the rat was studied using both morphometric and electroneurophysiologic techniques. After a standardized localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UMP), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively. Observations were made after 20, 40 and 60 days of nerve regeneration for comparison with age-matched crushed or nonoperated controls. Electroneurophysiologic studies of right sural nerves were performed as single fibre measurements. Morphometry was performed on semithin transverse sections of the right common peroneal nerve with a fully automatic interactive image analysis system. Forty days after crush injury the single fibre conduction velocity of all type II afferents in the UMP/CMP treated group was significantly accelerated. There was a trend (10% greater than or equal to p greater than or equal to 5%) to increase of mean efferent single nerve fibre function at this time. Morphometry of nerve fibres revealed a trend to enlargement of mean fibre area and mean fibre diameter related to increased myelin area and myelin thickness. After 60 days, there was a trend to increase of single fibre conduction velocity of all type II afferents in the UMP/CMP treated group. Automated morphometry revealed a significant increase for the following parameters: fibre area, fibre diameter, myelin area, myelin thickness and axon area.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445473 TI - Effects of nicorandil on regional cerebral blood flow in patients with chronic cerebral infarction. Preliminary communication. AB - The effect of a single oral dose of nicorandil (N-2-(hydroxyethyl)-nicotinamide nitrate, CAS 65141-46-0) on the regional cerebral blood flow (rCBF) was studied in 9 patients with cerebral infarction. The rCBF was measured by the Xe-133 inhalation method before and after a single oral 10 mg dose of nicorandil. Mean arterial blood pressure (MABP) was mildly but significantly decreased. PeCO2 did not change significantly. Mean rCBF was significantly increased by 20.9% after administration of nicorandil (p less than 0.05). No significant correlation between percentage change in the MABP and percentage change in the rCBF was observed. These results indicate that nicorandil is not just a coronary vasodilator, but also possesses beneficial effects on the cerebral circulation in patients with cerebral infarction. PMID- 1445474 TI - Pretreatment anxiety level as differential predictor in outpatients with panic disorder. AB - The pretreatment anxiety level is supposed to be a very important unspecific treatment factor. Main purpose of this study is to test whether the patients' pretreatment anxiety level is a general or a specific predictor of treatment response and whether mildly, moderately, and severely anxious patients can be differentially characterized by other diagnostic and clinical variables. 103 patients (37 males, 66 females; mean +/- sd age 35.6 +/- 9.5 years), a subsample of the Second Phase of the Cross-National Collaborative Panic Study, were included in the present study. A high positive correlation of initial anxiousness with the number of panic attacks at the end of treatment was found, moreover high positive correlations with most other baseline assessments. Initially severely anxious patients are the severest ill patients with the least treatment response, and that in all treatment groups. The pretreatment anxiety level predicts the number of panic attacks as well as the degree of avoidance behavior in both drug groups, whereas it predicts anticipatory anxiety intensity in the placebo group. PMID- 1445475 TI - Use of an in vitro absorption model system for predicting sustained release of verapamil. AB - It is shown that it is possible to characterize sustained release formulations in vitro using not only dissolution data but also an absorption model system. The mean dissolution time (MDT) has been shown to be a suitable parameter for evaluating sustained release formulations in vitro. t1/2 and mean residence time (MRT) have been shown to be convenient pharmacokinetic parameters for characterizing sustained release formulations. For comparing in vitro and in vivo results the quotients MDT normal/MDT retard and MRT normal/MRT retard do seem to be useful. PMID- 1445476 TI - Controlled study on the therapeutic efficacy of propionyl-L-carnitine in patients with congestive heart failure. AB - A double-blind phase II study of propionyl-L-carnitine (CAS 17298-37-2) versus placebo was carried out on a group of 60 patients with mild to moderate (II and III NYHA class) congestive heart failure. The group was made up of men and women aged between 48 and 73 years in chronic treatment with digitalis and diuretics for at least 3 months and who still displayed symptoms. Thirty of these patients were chosen randomly and for 180 days, 500 mg of propionyl-L-carnitine was orally administered, 3 times a day in addition to their usual treatment. At basal conditions and after 30, 90 and 180 days the maximum exercise time was evaluated using an exercise tolerance test performed on an ergometer bicycle and the left ventricular ejection fraction was tested by means of bidimensional echocardiography. After one month of treatment, the patients treated with propionyl-L-carnitine, compared to the control group, showed significant increases in the values of both tests, increases which became even more evident after 90 and 180 days. At the stated times the increases in the maximum exercise time were 16.4%, 22.9%, and 25.9%, respectively. The ventricular ejection fraction increased by 8.4%, 11.6% and 13.6%, respectively. On the basis of these results, having studied the particular mechanism of action of propionyl-L carnitine the authors conclude that it represents a drug of undoubted therapeutic interest in patients with congestive heart failure, in whom it could be efficaciously administered along with a standard pharmacological therapy. PMID- 1445477 TI - Pharmacokinetics and antihypertensive effect of oral pelanserin in renal hypertensive dogs. AB - The pharmacokinetics and antihypertensive effect of pelanserin (CAS 2208-51-7), a 5-HT2- and alpha 1-antagonist, were studied during repetitive administration (0.5 mg/kg, p.o., b.i.d.) in renal hypertensive dogs. After the first dose, pelanserin was absorbed reaching a Cmax value of 39.6 +/- 9.01 ng/ml at a tmax of 2.58 +/- 0.74 h. The steady state of plasma levels was reached between the 3rd and 15th doses of pelanserin. Pharmacokinetic parameters calculated after the 47th dose of pelanserin were Cmax(ss) of 147.15 +/- 35.88 ng/ml at a tmax(ss) of 3.17 +/- 1.02 h, AUC(0-12 h) of 593.80 +/- 106.96 ng.h/ml and a terminal half-life of 18.02 +/- 2.94 h. The accumulation ratio determined as Cmin(ss)/Cmin1 was 2.36 +/- 0.43 and was similar to that calculated in basis to the terminal half-life 2.67 +/- 0.37. On the other hand, pelanserin produced blood pressure decrease with two different profiles. After the first dose an acute antihypertensive effect was observed which reached a maximum of 20 mmHg in about 3 h; then blood pressure recovered gradually arriving to basal values at 12 h. When administered repetitively, pelanserin produced a gradual reduction in blood pressure which reached its maximum at 15 days. After the last dose, blood pressure basal values were about 20 mmHg lower than pretreatment levels and remained almost unchanged during 48 h after the last dose. It is concluded that pelanserin pharmacokinetic and pharmacodynamic profiles in dogs are adequate for an antihypertensive agent, therefore this drug possesses potential therapeutic usefulness in the treatment of hypertension. PMID- 1445478 TI - Relative efficacy and safety of loratadine, hydroxyzine, and placebo in chronic idiopathic urticaria. AB - The efficacy and safety of a new non-sedating antihistamine, loratadine (Clarityn, CAS 79794-75-5) 10 mg q.d., was compared to the classical antihistamine, hydroxyzine 25 mg t.i.d. and placebo in a 4-week (optional 12 week) randomized, double-blind, multi-center study in 203 patients with chronic idiopathic urticaria. Efficacy evaluations included weekly physician and patient assessments of pruritus, overall disease condition, and therapeutic response to treatment. Loratadine and hydroxyzine were significantly more effective than placebo and clinically comparable to each other as measured by all efficacy evaluations at each visit. Loratadine was safe and well tolerated with sedation and dry mouth similar to placebo and significantly less than hydroxyzine. PMID- 1445479 TI - Percutaneous absorption of methylprednisolone aceponate after single and multiple dermal application as ointment in male volunteers. AB - Six healthy, elderly volunteers were treated once daily with Advantan ointment containing 0.1% of methylprednisolone aceponate (MPA, CAS 86401-95-8) in an area dose of 5 mg ointment/cm2 on a marked area of 80 cm2 of intact skin on the back for 14 days. The ointments used for treatment on days 1 and 8 contained 14C-MPA with a specific radioactivity of 2.5 MBq/mg MPA. Following the radioactive pulse doses, the concentrations of 3H-radioactivity in plasma and urine were monitored up to 48 h and 7 days, respectively. The concentration of 14C-radioactivity in the plasma did not exceed the limit of detection of 0.3 ng MPA-equiv./ml. Percutaneous absorption of MPA through intact skin was small (les than 1%) and did not change during repeated application, indicating that the penetration barrier is not influenced by the drug or the vehicle. PMID- 1445480 TI - Hypolipidaemic activity of a novel acyclic ansamycin derivative. Synthesis and pharmacokinetic and pharmacodynamic studies in rodents. AB - Certain classes of the antibacterial agent rifamycin SV have recently been shown to possess marked hypolipidaemic activity. An acyclic oxazolylrifamycin has been prepared and its hypolipidaemic properties evaluated; it was found to be significantly more potent when administered orally to Wistar and Sprague-Dawley rats than other previously described rifamycin hypolipidaemics. The plasma decay rate of a bolus of intravenously administered 125I-LDL (low density lipoprotein) was significantly greater in treated rats than in rats receiving vehicle alone, compatible with a drug-induced increase in LDL catabolism. A bolus of radiolabelled drug was rapidly removed from the circulation by the liver, the presumed target organ. Compound 3 constitutes the first example of a new class of acyclic hypolipidaemic ansamycins. PMID- 1445481 TI - Influence of protein binding on the metabolic clearance rate of synthetic progestins in the rat liver perfusion model. AB - Levonorgestrel (LN), 3-Keto-desogestrel (KDG), norethisterone (NET), and gestodene (GST) were investigated in the recirculating rat liver perfusion model. Progestins were dissolved in buffered salt solution (MI), BSA containing (MII) or HSA and sex hormone binding globulin (SHBG) containing medium (MIII) at a concentration of about 60 ng/ml. Each 3-5 female rat livers were perfused with MI, MII, and MIII for 1 h. Perfusion medium, liver biopsies and total bile were analyzed for progestin levels by specific radioimmunoassays. Protein binding characteristics were determined in media and tissue. In all experiments bile (remaining liver) contained less than 1% (3%) of respective progestin dose demonstrating an almost complete biotransformation of all drugs by rat livers, irrespective of used medium. With MI, metabolic clearance rates (MCRs) and half lives (t1/2) were not different for the four progestins. With MII, the actual progestin levels were generally higher than with MI, but half-lives were not changed. MCRs were close to the perfusion rate at the start of experiments but decreased to about 50%. MCRs of free and total drug levels were identical. Protein binding of 70-80% did not change with time. With MIII, the half-lives increased 1.5 fold (NET), 2.8 fold (KDG), 3.1 fold (GST) and 3.2 fold (LN) and MCRs accounted for 50-70% of perfusion rate at the beginning. The time courses of further MCR decreases were different for the various progestins and can be attributed to differences in specific binding of drugs to SHBG. Clearly, the presence of SHBG in MIII induced a shift of drug from liver tissue into the perfusion medium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445482 TI - Pharmacokinetics and serum protein binding of gestodene and 3-keto-desogestrel in women after single oral administration of two different contraceptive formulations. AB - Two low-dose oral contraceptives, both containing the same dose of ethinyl estradiol (EE2, CAS 57-63-6) but different progestins--gestodene (CAS 60282-87-3) and desogestrel (CAS 54024-22-5), respectively--were administered to 18 women in a single dose, cross-over study. The serum concentrations of gestodene (GEST, one of the components of Femovan) and 3-keto-desogestrel (KDG) have been measured by specific radioimmuno-assays and the pharmacokinetics of both progestins were assessed. The serum protein binding of both compounds was also investigated and although the free fraction was the same for GEST and KDG, the distribution with respect to the binding proteins albumin and sex hormone binding globulin (SHBG) was slightly different. GEST was mainly bound to SHBG, while KDG was predominantly bound to albumin. Maximum concentrations of GEST were observed after 0.7 +/- 0.2 h and amounted to 4.9 +/- 2.4 ng/ml. A biphasic pattern of disposition was observed, with half lives of 0.13 +/- 0.06 h and 14.6 +/- 4.2 h, respectively. The AUC was 32.9 +/- 18.3 ng.ml-1.h. For KDG, maximum serum levels of 1.7 +/- 0.8 ng/ml were observed 1.5 +/- 0.8 h post administration. Drug levels declined with half-lives of 0.5 +/- 0.2 h and 17.0 +/- 9.3 h, respectively, and the AUC was 15.2 +/- 10.9 ng.ml-1.h. PMID- 1445483 TI - Pharmacokinetics and serum protein binding of 3-keto-desogestrel in women during three cycles of treatment with a low-dose combination oral contraceptive. AB - The serum concentrations of 3-keto-desogestrel have been measured in 43 women who took a low-dose oral contraceptive containing 30 micrograms ethinyl estradiol (CAS 57-63-6) together with 150 micrograms desogestrel (CAS 54024-22-5) for a period of 3 months. Basic pharmacokinetic parameters, like Cmax, tmax and AUC, as well as the serum protein binding of 3-keto-desogestrel were determined on days 1, 10 and 21 of the first and the third treatment cycle, respectively. During cycle one, Cmax, AUC(0-4h) and AUC(0-24h) values on day 1 were 1.9 +/- 0.7 ng/ml, 3.9 +/- 1.3 ng.ml-1.h and 12.4 +/- 5.7 ng.ml-1.h, respectively. These values increased to 4.7 +/- 2.0 ng/ml, 12.1 +/- 5.6 ng.ml-1.h and 47.3 +/- 26.0 ng.ml 1.h on day 21. Within cycle 3, a similar, although less steep increase was observed for these parameters and there was practically no difference in the values of corresponding parameters on day 21 of both cycles. Throughout treatment, there was a redistribution of 3-keto-desogestrel with respect to the binding proteins albumin and sex hormone binding globulin (SHBG). During cycle 1, the free fraction decreased from 1.8% on day 1 to 1.1% on day 21, and the SHBG bound fraction increased at the same time from 40% to 62%, mainly at the expense of the albumin-bound fraction. During cycle 3, there were only minor changes as compared to cycle one. The observed changes in the serum protein binding were related to an increase in SHBG levels during the treatment period. PMID- 1445484 TI - Pharmacokinetics and protein binding of gestodene under treatment with a low-dose combination oral contraceptive for three months. AB - The serum concentrations of gestodene (CAS 60282-87-3) as well as the binding of this progestin to serum proteins were studied in 40 women who took a low-dose oral contraceptive (Femovan, Femodene) containing 30 micrograms ethinyl estradiol (CAS 57-63-6) and 75 micrograms gestodene for 3 months. On days 1, 10, and 21 of the first and the third treatment cycle, respectively, 7 blood samples were drawn before and up to 4 h after pill intake; additional samples were taken prior to morning ingestion of pill on days 2, 5, 11, 15 and 22 of these cycles. Gestodene levels were measured by means of a specific radioimmunoassay and were evaluated for Cmax, tmax, and AUC up to 4 and 24 h. Independent of the test day and the treatment cycle studied, mean maximum gestodene serum levels were found about 0.8 to 0.9 h after pill intake. During the first treatment cycle, mean values of Cmax, AUC(0-4h), and AUC(0-24h) amounted to 4.3 ng.ml-1, 9.3 ng.ml-1.h, and 27.3 ng.ml-1.h on test day 1; these values increased by 250-400% and by 300-500%, respectively, when days 10 and 21 were compared to day 1. On day 1 of the third treatment cycle, these pharmacokinetic parameters were higher by almost a factor of two as compared to the corresponding data obtained on the beginning of the first cycle whereas the increase of these values between day 1 and the subsequent test days (200-300%) was slightly lower in cycle 3 as compared to cycle 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445485 TI - Synthesis of the orally macrofilaricidal and stable glycerolipidic prodrug of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl)amino)phenylalaninoyl)gl ycerol. AB - A new strategy is presented to develop macrofilaricidal compounds orally administered and able to concentrate in the lymphatic system. A diglyceride derivative of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2'' chloroethyl)amino)phenylalaninoyl)gl y cerol, was synthesized. The esterification of melphalan by 1,3-dipalmitin allowed chemical stabilization of the alkylating agent in aqueous dispersion. No degradation of this prodrug was observed after a 3-month storage of an aqueous dispersion at 4 degrees C. The filaricidal activity of the prodrug was compared with those of melphalan in vitro against adults, infective larvae and microfilariae of Molinema dessetae, and evaluated in vivo on Molinema dessetae infected Proechimy oris. In vitro, melphalan and the glycerolipidic prodrug were inactive against microfilariae but active at 1 mmol/l against infective larvae and adults. In vivo studies were performed with rodents subcutaneously inoculated with infective larvae from Aedes aegypti. The number of macrofilariae was significantly reduced following treatment with a single oral dose of the alkylating agent prodrug (0.082 mmol/kg). PMID- 1445486 TI - In vitro activity of taurolidine, chlorophenol-camphor-menthol and chlorhexidine against oral pathogenic microorganisms. AB - The antimicrobial activity of taurolidine (Taurolin, CAS 19388-87-5), a synthetic broad-spectrum antimicrobial agent and anti-toxin, and two conventional antiseptics, chlorophenol-camphor-menthol (CCM) and chlorhexidine digluconate (CHX) were compared using the serial dilution test on 10 potential oral pathogenic bacterial species. The minimum inhibitory and minimum bactericidal concentrations were lowest for CHX (MIC 0.03-0.12 mg/ml), followed by taurolidine (MIC 0.12-0.5 mg/ml) and CCM (MIC 0.5-2.0 mg/ml). However, if both bacterial efficacy and cytotoxicity are considered, only taurolidine achieves extensive bactericidal activity with tissue tolerability. PMID- 1445487 TI - Pharmacokinetics of nicotine and cotinine after application of two different nicotine patches under steady state conditions. AB - Tobacco use has resulted in major health related problems world-wide. Transdermal nicotine replacement therapy is one of the most promising strategies in smoking cessation. In the present trial the pharmacokinetic properties of two matrix patches (A and B) were characterized and compared after daily application on day 4. Predose nicotine concentrations on day 4 with patch B were higher than with patch A (12.7 +/- 9.5 ng/ml vs. 8.3 +/- 5.3 ng/ml). With patch A there was a steeper increase up to the peak level, followed by a decline gradually up to 24 h. 24 h after application predose levels were reached again, demonstrating absence of significant accumulation of nicotine. The calculated elimination half lives of nicotine (3.4 +/- 1.8 h after patch A and 3.3 +/- 2.0 h after patch B) were longer than after i.v. application (published values range from 40 to 120 min). Under steady state cotinine concentrations remained constant. PMID- 1445488 TI - Resistance mechanisms in murine tumors with acquired multidrug resistance. AB - Mechanisms of multidrug resistance were studied in murine leukemia (L 1210) and sarcoma (Sa 180) tumors after pretreatment with anthracyclines in vivo. Despite identical pretreatment protocols, a considerable difference in the level of resistance between L 1210 and Sa 180 tumors was noted (for doxorubicin: 45-fold versus 340-fold; for daunorubicin: 51-fold versus 275-fold). However, no difference in mdr 1 gene-amplification and the overexpression of mdr 1-RNA or P glycoprotein was demonstrated. None of these parameters did increase by further treatment with a higher concentration of anthracyclines. Resistant sublines of Sa 180 revealed an overexpression of glutathione S-transferase-pi (GST-pi) in comparison to the parental line, whereas in sensitive and resistant sublines of L 1210 tumors the expression of GST-pi was similar. In order to study whether trifluoperazine can reverse the P-glycoprotein mediated component of multidrug resistance, trifluoperazine and doxorubicin were tested in vitro in L 1210 and Sa 180 cells. In contrast to the complete reversal of resistance in L 1210 tumors, resistance in Sa 180 was only partly circumvented. However, by buthionine sulfoximine treatment, the toxicity of multidrug resistant Sa 180 tumors could be increased. It was possible to reverse the resistance of Sa 180 tumors completely by trifluoperazine plus buthionine sulfoximine. Thus, multidrug-resistant Sa 180 tumors express different defense mechanisms whereas L 1210 tumors express only one defense mechanism (P-glycoprotein). PMID- 1445489 TI - Distribution of low density lipoprotein in the branch and non-branch regions of the aorta. AB - Atherosclerosis occurs focally in branch segments of the artery. Understanding why these segments are more susceptible to the development of the disease is at the root of understanding atherogenesis. We investigated accumulation of low density lipoprotein (LDL) in the branch and non-branch regions of the aorta to determine why the disease develops in branch regions. Abdominal aortas and their major branches were harvested from 36 rabbits. Rabbit LDL was prepared from whole blood and radiolabeled with 125I. The aorta was incubated with radiolabeled LDL in the lumen at 37 degrees C, under intraluminal pressure of 2-3 mmHg, for 1 h. Disks of 1.8 mm diameter were punched from the branch and non-branch regions of the aorta, cryosectioned and the sections counted in a gamma counter. Protein bound radioactivity was determined by TCA precipitation. LDL accumulation was highest towards the aortic intima and declined sharply towards the media. LDL accumulation at any given depth was higher in the branch than non-branch region. LDL accumulation in the intimal-medial sections was 87% higher in the branch than non-branch region. Total LDL accumulation in the branch was almost twice that in the non-branch region. Mean LDL accumulation was also greater in the branch than non-branch region. The aorta was significantly thicker at the branch. LDL distribution profiles indicate that LDL is present in a greater concentration and over a greater depth in the branch than non-branch region. The tendency of the branch region to accumulate LDL in greater amounts may explain its susceptibility to atherosclerotic lesion development. PMID- 1445490 TI - Effect of low-dose probucol therapy on LDL oxidation and the plasma lipoprotein profile in male volunteers. AB - The effect of 4 months of low-dose probucol treatment (250 mg/day) on LDL oxidation and on plasma-HDL cholesterol was studied in a prospective, double blind, randomized, placebo-controlled trial involving 26 male volunteers. LDL samples isolated at baseline and at 4 months were subjected to in vitro tests of LDL oxidation, involving copper-catalyzed, time-course experiments. For the placebo group, LDL oxidation did not significantly change over the 4-month period. However, in the probucol group, LDL oxidation was significantly inhibited at 4 months, as evidenced by assays measuring conjugated diene formation, lipid peroxide production and altered electrophoretic mobility of oxidized LDL. In fact, in the probucol group the 'lag-phase' of oxidation was prolonged 2.7-fold. Neither probucol nor placebo had a significant effect on plasma HDL-cholesterol: in the probucol group HDL-cholesterol fell from 37.7 +/- 7.4 mg/dl to 34.2 +/- 8.3 mg/dl (percentage decrease -8.9), while in the placebo group plasma HDL cholesterol levels were 42.4 +/- 8.3 mg/dl and 40.9 +/- 7.0 mg/dl at baseline and 4 months (percentage decrease -2.7). Therefore, a low dose of probucol (250 mg/day) given daily seems to afford protection against the oxidative modification of LDL, and does not appear to exert any substantial effect on the plasma lipoprotein profile. PMID- 1445491 TI - Transforming growth factor-beta 1 and interleukin-1 beta stimulate LDL receptor activity in Hep G2 cells. AB - The effect of transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 beta (IL-1 beta) on LDL receptor in Hep G2 cells was investigated. A greater than two-fold stimulation of the binding and internalisation of [125I]-labelled LDL at 37 degrees C was observed after an 18-h incubation of the cells with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml compared with control cells. Scatchard analysis of the binding of [125I]-labelled LDL at 4 degrees C after an 18-h incubation of the cells with 1170 units/ml IL-1 beta and 5 ng/ml TGF-beta 1 showed that they were both acting primarily by increasing LDL receptor number. The increase in LDL receptor activity could not be attributed to an increase in cell proliferation as TGF-beta 1 at concentrations from 0.05 ng/ml to 50 ng/ml had no significant effect on either cell number or [3H]thymidine incorporation into DNA whilst IL-1 beta inhibited DNA synthesis by more than 80% at a concentration of 11,700 units/ml but had significant effect on cell number. Cholesterol biosynthesis from [14C]acetate, in contrast to the stimulation of LDL receptor activity, was inhibited by approximately two-fold by incubation with TGF beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml. PMID- 1445492 TI - Paradoxical response of plasma lipoprotein(a) in patients undergoing cardiopulmonary bypass. AB - Plasma lipid, lipoprotein and apolipoprotein levels are known to decrease after major surgery. Coronary artery bypass surgery additionally involves use of extracorporeal circulation by use of a cardiopulmonary bypass pump, which necessitates hemodilution due to saline dextrose infusion to prime the pump. To investigate changes in lipids, lipoproteins and apolipoproteins as well as changes in C-reactive protein and albumin we conducted a study on 22 patients undergoing cardiac surgery involving cardiopulmonary bypass. Timed arterial blood samples were taken before, during and after cardiopulmonary bypass. At the onset and during cardiopulmonary bypass a rapid and significant fall was observed in all lipids and lipoproteins except lipoprotein(a) with recovery to near basal levels by 72 h for cholesterol, triglycerides, high density lipoprotein cholesterol and albumin, while apolipoproteins AI and B remained below basal levels during the postoperative period up to 72 h. In contrast, lipoprotein(a) levels increased at the onset, doubled during cardiopulmonary bypass and remained elevated postoperatively. On the other hand, C-reactive protein levels fell at the onset and during cardiopulmonary bypass but they became markedly elevated postoperatively. When results were corrected for hemodilution, the response patterns remained unchanged. As lipoprotein(a) is both atherogenic and thrombogenic, its elevation during cardiopulmonary bypass may be clinically important. PMID- 1445493 TI - Acute physical exercise alters apolipoprotein E and C-III concentrations of apo E rich very low density lipoprotein fraction. AB - To evaluate the influence of exercise on the apolipoprotein (apo) composition of very low density lipoprotein (VLDL) subfractions, we exercised 6 sedentary men for 30 min, 1 h after a fatty meal. VLDL fractions from samples drawn 4, 6 and 8 h post-prandially were separated from pre-stained plasma by high performance liquid chromatography and fractionated to apo E-poor (heparin-unbound) and apo E rich (heparin-bound) fractions. The postprandial peak area (volts) and apo E, C II and C-III concentrations (mg/dl) of post-exercise VLDL fractions were compared with corresponding postprandial values obtained at rest. Plasma triglycerides (TG) levels (mg/dl) were significantly lower 4 (P < 0.05), 6 (P < 0.02) and 8 h (p < 0.05) postprandially; the apo E-poor VLDL fraction was not modified by exercise and its apo concentrations were in the low range of detection; the apo E rich VLDL peak area significantly decreased 4 (P < 0.01), 6 (P < 0.01) and 8 h (P < 0.05) postprandially; the apo E concentration of apo E-rich VLDL was significantly lower 4 (P < 0.02) and 6 h (P < 0.05) postprandially; the apo C-III concentration of apo E-rich VLDL significantly increased, 4 and 6 h postprandially (P < 0.05). Apo E-rich VLDL is, presumably, the metabolically active fraction of the particle and may regulate plasma TG level following exercise. The metabolic role of apo E-poor VLDL remains to be defined. PMID- 1445494 TI - Probucol reduces plasma lipid peroxides in man. AB - Although primarily used as a lipid lowering drug, probucol also possesses anti oxidant activity and has been shown in animal models to inhibit or delay the progression of atherosclerosis. It has been suggested that this anti atherosclerotic effect may occur through inhibition of free radical oxidation of low density lipoprotein. The aim of this study was to investigate the effects of probucol on free radical activity in hyperlipidaemic patients. Plasma lipid peroxides were measured before probucol treatment, at 4 and 12 weeks treatment and then 4 weeks after stopping probucol. Lipid peroxide concentrations were significantly reduced during and 4 weeks after stopping treatment with probucol, when compared with baseline values. There were no changes in plasma vitamin E concentrations. The results of this study indicate that probucol reduces lipid peroxidation in patients, an effect which may occur through a free radical scavenging action. PMID- 1445495 TI - Hageman factor and risk of myocardial infarction in middle-aged men. AB - In order to evaluate whether Hageman factor (XII) is increased in survivors of myocardial infarction and whether this in turn influences factor VII coagulant activity (VIIc), we examined the coagulation and lipoprotein profiles in 82 subjects, 51 of whom had a definite history of myocardial infarction and 31 healthy volunteers invited from a local general practice register for a cardiovascular screen. Both serum cholesterol (P = 0.03) and plasma fibrinogen levels (P = 0.02) were significantly elevated in cases compared with controls. There were no significant differences in coagulant activities, and in particular factor XII concentration was not significantly different between groups. Furthermore, in 47 of the subjects, 28 of whom had a history of myocardial infarction, a more detailed analysis, including measurement of VIIc after overnight incubation of plasma at 4 degrees C, was undertaken. Approximately half the subjects in either group showed some evidence of activation, though history of myocardial infarction was not in itself a significant predictor of this. All measures of XII concentration related positively to VIIc after cold activation, the strongest being the measure of amidolytic activity following activation of factor XII (XIIAm) (r = 0.5, P < 0.01). In addition, XIIa, a measure of activity due to enzymes derived from factor XII, related strongly to many of the measured lipoprotein variables, particularly VLDL cholesterol and triglycerides, supporting the hypothesis that negatively charged molecules such as free fatty acids on larger lipoprotein particles provide the contact surface necessary to activate factor XII. The findings confirm the importance of this alternative pathway in leading to activation of factor VII. PMID- 1445496 TI - Interferon-gamma suppresses PDGF production from THP-1 cells and blood monocyte derived macrophages. AB - Involvement of the immunological mechanisms in atherogenesis has recently been suggested by immunohistological detection of macrophages and T lymphocytes in atherosclerotic lesions. In the present study, we have investigated the regulatory effect of interferon-gamma (IFN-gamma), a cytokine secreted by activated T cells, on the production and secretion of platelet-derived growth factor (PDGF) from macrophages in culture. The human monocytic leukemia cell line, THP-1, was treated with phorbol 12-myristate 13-acetate (PMA) for 24 h to induce macrophage differentiation and PDGF production, and then various doses of recombinant human IFN-gamma (0-1000 I.U./ml) were added to the culture. After 48 h, the conditioned medium and the cells were harvested and analyzed for PDGF production. PDGF-dependent mitogenic activity in the conditioned medium, estimated by neutralization of mitogenic activity with anti-PDGF antibody, was suppressed by IFN-gamma treatment. Radioimmunoassays for PDGF also revealed a decrease in both PDGF-AA and -BB in the conditioned medium with IFN-gamma treatment, whereas neither total cell DNA as an indication of cell number nor overall protein synthesis based on [3H]leucine incorporation were decreased. Northern analysis of total RNA extracted from the cells demonstrated that IFN gamma suppressed the level of PDGF mRNA. Analysis of mRNA degradation in the presence of actinomycin D demonstrated that the decrease in PDGF mRNA was not due to enhanced degradation of mRNA. A similar inhibitory effect of IFN-gamma on PDGF mRNA levels was also found in monocyte-derived macrophages cultured in the presence of granulocyte-macrophage colony stimulating factor. These results suggest that IFN-gamma modulates production and secretion of PDGF from macrophages and that the functions of macrophages in atherogenesis may be regulated by the cellular interactions between T cells and macrophages through the action of cytokines such as IFN-gamma. PMID- 1445497 TI - An oxidative mechanism is involved in high glucose-induced serum protein modification causing inhibition of endothelial cell proliferation. AB - In order to investigate the role of hyperglycemia on the development of atherosclerosis in diabetics, the effects of high glucose-induced modification of serum factors on the proliferation of bovine carotid artery endothelial cells were studied. Dialysates of high glucose-treated serum inhibit cell growth in a time- and glucose concentration-dependent manner. With 6 weeks of pretreatment, 16.7 mM glucose causes a 47.2% inhibition in cell growth compared to 5.6 mM glucose (P < 0.001). Pretreatment of serum in the presence of reduced glutathione (0.5-1.0 mM), an antioxidant, significantly prevents the high glucose-induced inhibition without inhibiting the formation of early non-enzymatic glycosylation products. Dithiothreitol (7.5 mM) treatment after preincubation with glucose fully restores the glucose-induced inhibition. When the dialysates are fractionated according to molecular mass, the high glucose-induced inhibition is maximal in the MW fraction above 100 kDa. These data suggest that high glucose conditions facilitate the susceptibility of serum proteins to sulfhydryl oxidation forming disulfide crosslinks and this oxidative process may contribute to the inhibition of endothelial cell proliferation. PMID- 1445498 TI - Homocysteine catabolism: levels of 3 enzymes in cultured human vascular endothelium and their relevance to vascular disease. AB - Elevated plasma homocysteine enhances the risk of thrombosis and premature arteriosclerosis. We have assessed the activity of the 3 prime enzymes of homocysteine metabolism in cultured human venous endothelial cells, in a study of their possible protective roles. In cells from 4 individuals, cultured in Dulbecco's modified Eagle medium, the mean activity +/- S.D. of cystathionine beta-synthase (nmol of product/h per mg of cell protein, at 37 degrees C) was 3.58 +/- 3.11 at pH 8.6. The assay used was our newly developed amino acid analyser-based procedure. The activity of 5-methyltetrahydrofolate:homocysteine methyltransferase at pH 7.4 was 4.12 +/- 1.25 and betaine:homocysteine methyltransferase (BHMT) was undetectable (< 1.4 nmol/h per mg protein). Cells were also cultured in a medium aimed at stimulating methionine biosynthesis, containing methionine-deficient Dulbecco's modified Eagle medium to which L homocystine (100 mumol/l) and methylcobalamin (1 mumol/l) had been added. In these cells 5-methyltetrahydrofolate:homocysteine methyltransferase activity increased to 7.95 +/- 1.45, P < 0.001, there was a non-significant decrease in cystathionine beta-synthase activity to 2.16 +/- 1.52 and BHMT activity was still undetectable. These cells were more resistant to in vitro homocysteine-induced detachment than were cells from the same line cultured in Dulbecco's modified Eagle medium alone. Our findings establish that human endothelial cells express 2 of the 3 primary enzymes of homocysteine catabolism. They suggest that persons who are deficient in cystathionine beta-synthase or 5 methyltetrahydrofolate:homocysteine methyltransferase activity may not only develop homocysteinemia, but also have vascular endothelium which is more susceptible to damage by homocysteine than persons with normal enzyme levels. PMID- 1445499 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 1-1992. A 34-year-old woman with dyspnea and multiple small cystic areas in the lungs. PMID- 1445500 TI - Results of a randomized trial of partner notification in cases of HIV infection in North Carolina. AB - BACKGROUND: We sought to compare two methods of notifying sex partners of subjects infected with the human immunodeficiency virus (HIV) or persons who had shared needles with them (needle-sharing partners): "patient referral," in which the responsibility for notifying partners was left to the patient, and "provider referral," in which providers attempted to notify partners. METHODS: Names of sex partners and needle-sharing partners and information on how to locate them were obtained from consenting HIV-infected subjects identified in the HIV-testing programs at three public health departments in North Carolina. The subjects were randomly assigned to a patient-referral group (in which patients had the initial responsibility for notifying their partners) or a provider-referral group (in which the study counselor notified the partners). The success of attempts to notify partners was monitored by means of interviews with counselors conducted both in the field and at the health department. RESULTS: Of 534 HIV-positive persons identified at the health departments, 247 (46 percent) did not return for counseling after the test, 8 were counseled outside the study, and 117 (22 percent) were ineligible. Of the 162 invited to participate, 88 (54 percent) declined and 74 (46 percent) agreed. The subjects were mostly male (69 percent), black (87 percent), homosexual or bisexual (76 percent of the men), and had a median age of 30 years. Thirty-nine were assigned to the provider-referral group and 35 to the patient-referral group. In the provider-referral group 78 of 157 partners (50 percent) were successfully notified, whereas in the patient-referral group only 10 of 153 (7 percent) were notified. Of the partners notified by the counselors, 94 percent were not aware that they had been exposed to HIV. Overall, 23 percent of the partners notified and tested were HIV-positive. CONCLUSIONS: In this trial, leaving the notification of partners up to the subjects (patient referral) was quite ineffective, despite the North Carolina law requiring that partners be notified. Partner notification by public health counselors (provider referral) was significantly more effective. Although the effectiveness of notification procedures is constrained by the accuracy of the information provided by HIV-infected patients, counselors who notify the partners of an infected patient can refer them to educational, medical, and support services targeted to persons at high risk for HIV infection and may encourage the adoption of less risky behavior. PMID- 1445501 TI - Nicotine enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. AB - Epidemiologic evidence of an inverse relationship between cigarette smoking and Parkinson's disease suggests that a component of cigarette smoke protects against nigrostriatal degeneration. Nicotine, a major component of cigarette smoke, is similar in chemical structure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and is metabolized in part by the same enzymes that detoxify MPTP. We investigated the effect of chronic nicotine on MPTP neurotoxicity in two strains of mice and found that nicotine increases rather than decreases MPTP toxicity. These results are not compatible with the hypothesis that nicotine is that component of cigarette smoke that protects against nigrostriatal degeneration, at least in the MPTP experimental model of Parkinson's disease. PMID- 1445502 TI - Inhalation fever: a proposed unifying term for febrile reactions to inhalation of noxious substances. PMID- 1445503 TI - Combined spinal-epidural anesthesia using the CSEN. PMID- 1445504 TI - What is pediatrics?: prenatal medicine to young adult care. PMID- 1445505 TI - Endoscopic transanal resection of large villous tumours of the rectum. AB - Endoscopic transanal resection (ETAR) is an innovative approach in the management of low lying tumours of the rectum. We report our experience of this technique in six elderly patients (mean age 74 years) with large villous adenomas, situated between 2 and 12 cm from the anal verge. There were no complications. One patient with a circumferential tumour has been spared the more conventional operation of abdominoperineal excision. Follow-up ranged from 6 to 30 months (mean 16 months) during which two recurrences were detected. These were adequately treated by further ETARs. It is concluded that ETAR is a simple and well-tolerated procedure and is a useful addition to the surgeon's armamentarium. PMID- 1445506 TI - Assessment of the use of disposable skin staplers in bowel anastomoses to reduce laparotomy time in penetrating ballistic injury to the abdomen. PMID- 1445507 TI - Clonal origin of bladder cancer. AB - BACKGROUND: Patients with cancer of the urinary bladder often present with metachronous tumors, appearing at different times and at different sites in the bladder. This observation has been attributed to a "field defect" in the bladder that allows the independent transformation of epithelial cells at a number of sites. We tested this hypothesis using molecular genetic techniques. METHODS: We examined 13 tumors from cystectomy specimens from four women, using a method that analyzes the pattern of X-chromosome inactivation to determine whether the tumors were derived from the same precursor cell. In addition, we analyzed allelic loss on autosomes to determine whether different tumors had the same genetic alterations. The alterations evaluated included the loss of chromosome 9q sequences (commonly found in superficial bladder tumors) and the loss of 17p and 18q sequences (usually found only in advanced tumors). RESULTS: For each patient studied, all the tumors had inactivation of the same X chromosome, whereas normal bladder mucosa cells had random patterns of inactivation. Moreover, each tumor that could be evaluated from a given patient had lost the same allele on chromosome 9q, suggesting that the loss of this allele preceded the spread of neoplastic cells elsewhere in the bladder. The losses of chromosome 17p and 18q alleles, which are late events in tumor progression, were not common to different tumors from the same patient. CONCLUSIONS: A number of bladder tumors can arise from the uncontrolled spread of a single transformed cell. These tumors can then grow independently with variable subsequent genetic alterations. PMID- 1445508 TI - Laparoscopic cholecystectomy in perspective. PMID- 1445509 TI - Factors influencing cosmetic outcome and complication risk after conservative surgery and radiotherapy for early-stage breast carcinoma. AB - PURPOSE: The study was undertaken to assess the relationship among cosmesis and complications to factors related to disease presentation, surgical and radiotherapeutic technique, and adjuvant systemic therapy in conservative treatment for early-stage breast carcinoma. PATIENTS AND METHODS: Between 1982 and 1988, 234 women with stage I/II breast carcinoma were treated with conservation therapy by a highly standardized protocol of limited excision and radiotherapy. Radiation boost and/or reexcision were determined by careful quantitation of the normal tissue margin around the primary tumor. Boosts to 20 Gy were preferentially performed with interstitial iridium-192 (192Ir) implants. Axillary node dissections were performed in all patients aged less than 70 years. Adjuvant therapy consisted of cyclophosphamide, methotrexate, (doxorubicin), and fluorouracil (CM[A]F) six to eight times for node-positive premenopausal women and tamoxifen for node-positive or -negative postmenopausal women. Median follow up was 50 months (range, 20 to 80 months). Cosmesis was graded by defined criteria, and complications were individually scored. RESULTS: Factors found to impact cosmesis adversely were palpable tumors (P = .046), volume of breast tissue resected (P = .027), reexcision of the tumor bed (P = .01), number of radiation fields (P = .03), radiation boost (P = .01), and chest wall separation (P = .01). There was a trend toward worse cosmesis (P = .062) in patients receiving tamoxifen. Cosmesis was not adversely affected by interstitial implant in spite of a higher prescribed dose. Factors influencing complication risk were axillary node dissection (P = .02), number of lymph nodes harvested (P = .05), and chemotherapy (P = .03). CONCLUSIONS: Optimal cosmesis and minimal complication risk require careful attention to the technical details of surgery and radiotherapy. The impact of systemic therapies needs to be more thoroughly examined. PMID- 1445510 TI - The centre thought to control sensory and motor activity in the early history of medicine. AB - In Ancient Greek medicine the heart instead of the brain was sometimes thought to be the organ co-ordinating sensory and motor activity. The history of the origin of this erroneous idea is outlined. The relative importance of observations and theory in early medical investigations is discussed, and the anatomical dissections leading to the establishment of the brain as the centre of sensory and motor function are described. PMID- 1445511 TI - Meatoscopy: a simple technique to examine the distal anterior urethra in men. AB - A common problem is to determine the site of the base of meatal warts in men and if the lesions will be suitable for the treatments available in genitourinary medicine (GUM) or sexually transmitted diseases (STD) clinics. Formal endoscopy requires sterile conditions and is therefore an expensive procedure. A simple safe cheap alternative is meatoscopy using an auroscope with inflation. This allows inspection of the anterior urethra to a depth of 5 or 6 cm. With this technique 175 examinations were performed on 153 patients. Warts were confined to the lips in 27 (56%) of 48 patients with meatal warts; in an additional 5 patients with meatal warts the warts arose from deep in the fossa navicularis and in 16 patients with meatal warts there were additional warts in the fossa navicularis invisible on clinical examination. No urethral warts were seen in 103 patients without meatal warts, comprising 47 patients with external genital warts and 56 without any warts. It is concluded that meatoscopy should be undertaken in all patients with meatal warts to determine the site of their base and to assess if there are any more proximal warts. This should be done as soon as the meatal warts are seen, and urethritis has been excluded, so that appropriate treatment can be planned. PMID- 1445512 TI - Surgery for stroke: an update. AB - Carotid endarterectomy was the most common vascular procedure in the USA in the 1980s. The last decade has witnessed a much-needed critical reappraisal of its role. Results from recent large-scale trials are now reported and will have a great influence on patient management. PMID- 1445514 TI - Oral sex and recurrent vulvo-vaginal candidiasis. PMID- 1445513 TI - Medical Research Council trial of treatment of hypertension in older adults: principal results. MRC Working Party. AB - OBJECTIVE: To establish whether treatment with diuretic or beta blocker in hypertensive older adults reduces risk of stroke, coronary heart disease, and death. DESIGN: Randomised, placebo controlled, single blind trial. SETTING: 226 general practices in the MRC general practice research framework. SUBJECTS: 4396 patients aged 65-74 randomised to receive diuretic, beta blocker, or placebo. Patients had mean systolic pressures of 160-209 mm Hg and mean diastolic pressures less than 115 mm Hg during an eight week run in and were not taking antihypertensive treatment. INTERVENTION: Patients were randomised to atenolol 50 mg daily; hydrochlorothiazide 25 mg or 50 mg plus amiloride 2.5 mg or 5 mg daily; or placebo. The regimens were adjusted to achieve specified target pressures. Mean follow up was 5.8 years. MAIN OUTCOME MEASURES: Strokes, coronary events, and deaths from all causes. RESULTS: Both treatments reduced blood pressure below the level in the placebo group. Compared with the placebo group, actively treated subjects (diuretic and beta blocker groups combined) had a 25% (95% confidence interval 3% to 42%) reduction in stroke (p = 0.04), 19% (-2% to 36%) reduction in coronary events (p = 0.08), and 17% (2% to 29%) reduction in all cardiovascular events (p = 0.03). After adjusting for baseline characteristics the diuretic group had significantly reduced risks of stroke (31% (3% to 51%) p = 0.04), coronary events (44% (21% to 60%), p = 0.0009), and all cardiovascular events (35% (17% to 49%), p = 0.0005) compared with the placebo group. The beta blocker group showed no significant reductions in these end points. The reduction in strokes was mainly in non-smokers taking the diuretic. CONCLUSION: Hydrochlorothiazide and amiloride reduce the risk of stroke, coronary events, and all cardiovascular events in older hypertensive adults. PMID- 1445515 TI - Lingual nerve injury following laryngoscopy. PMID- 1445516 TI - Advanced Chinese NiTi alloy wire and clinical observations. AB - Chinese NiTi wire was studied on the bench with six other nickel-titanium-alloy wires. Bending and torsional tests were conducted and temperatures of phase transformation compared. The Chinese NiTi wire was found to have a low stiffness, high springback and constant bending and torsional moments on unloading, in a very large deformation region. It can produce a gentle, nearly constant force. These factors make it desirable for clinical application. Included in this paper are clinical observations of case selected from over 100 patients in current treatment with Chinese NiTi wires. Chinese NiTi wire reduced the leveling and alignment phase of treatment without discomfort to the patient. Chinese NiTi wire can be used in both children and adults. PMID- 1445517 TI - Bacteremia and fungemia of unknown origin in adults. AB - Two hundred fifteen (23%) of 955 episodes of bacteremia (defined as including fungemia) detected in adult patients during 2 years were of unknown origin. Sixty six percent of episodes of unknown origin were hospital acquired. The median age of patients with bacteremia of unknown origin was 65 years, and their most common underlying disorders were solid malignancy (28% of patients) and diabetes mellitus (18%). Only three factors were associated with bacteremia of unknown origin (as opposed to episodes with a known source): peripheral venous catheterization, hemodialysis, and plasmapheresis. Gram-negative bacteria were isolated from the blood in 62% of episodes of unknown origin; 10% of episodes were polymicrobial. Staphylococci were isolated from 67% of patients undergoing hemodialysis and from 37% of those with diabetes; Pseudomonas species from 15% of patients with hospital-acquired episodes; and Candida species from 21% of patients with a central venous catheter. Fifteen percent of episodes in cancer patients were polymicrobial. Empirical antibiotic treatment was inappropriate in 49% of episodes of unknown origin and in 35% of episodes with a known source (P less than .001). Death rates were 44% and 25% in episodes of unknown and known origin, respectively. An unknown source of bacteremia was independently associated with a fatal outcome. PMID- 1445518 TI - The strange case of Ms Elizabeth Trevers who was affrighted to an astonishment. PMID- 1445519 TI - Trying times for human insulin. AB - The introduction of human insulin to treat diabetics seemed straightforward. What can account for the problems that have followed? PMID- 1445520 TI - Maimers, killers, and the universal death rate. PMID- 1445521 TI - The causes of low back pain. PMID- 1445522 TI - Ethical responsibilities toward wildlife. PMID- 1445523 TI - The comparative strengths of commercial glass-ionomer cements with and without metal additions. AB - Metal reinforced glass-ionomer cements are said to possess superior mechanical properties when compared to non-metal reinforced glass-ionomer cements. However, the literature to date does not always support this view, owing to the variety of materials and test methods employed. In this study the mechanical properties of three reinforced and three standard materials were tested using the standard specification tests of compressive and diametral strength in addition to tensile strength using the four point bend test. The tensile strength was also measured using the shell test in order that this test, which on theoretical grounds is more suited to these materials, may be evaluated. Six specimens of each material were prepared for each of the test modalities resulting in the conclusion that the addition of metal to glass-ionomer cements can markedly increase the strength of the materials. However, the method of fusing the metal to the glass rather than by simple addition does not produce any advantages in strength. In this evaluation one reinforced material was significantly stronger than all other materials in all four test modalities. The compressive strength test which appears in most standards does not appear to be very discriminatory. Of the tensile tests, which have more clinical significance, the results of the diametral strength tests, which are included in some standards, appear to be at variance with the other two tensile tests, suggesting that the flexural or shell test would be more appropriate. PMID- 1445524 TI - Interpreting Canada: models, mind-sets, and myths. PMID- 1445525 TI - Pneumococcal vaccine for Olympic athletes and visitors to Spain. PMID- 1445526 TI - ABC of colorectal diseases. Investigation of colorectal disorders. PMID- 1445527 TI - Study of diagnostic accord between general practitioners and an ophthalmologist. AB - OBJECTIVES: To identify diagnostic accord and disagreement between general practitioners and an ophthalmologist and thereby determine how undergraduate and non-specialist postgraduate ophthalmic training could be improved. DESIGN: Comparison of diagnosis of presenting conditions by general practitioners and one ophthalmologist in patients consulting general practitioners for ophthalmic problems during March 1989 to February 1990. SETTING: 12 general practices in west Nottingham. PATIENTS: 1474 patients presenting to the study general practitioners with new ophthalmic conditions or new episodes of recurrent conditions. MAIN OUTCOME MEASURES: Diagnoses of general practitioners and ophthalmologist. RESULTS: 1121 (76%) of patients with eye problems agreed to see the ophthalmologist and most were seen within three days. Sufficient data for comparison were available on 1103 patients. Diagnostic agreement was found in 638 cases (58%), but potentially serious misdiagnosis was found in only 15 cases; management in three of these cases would have ensured later identification. Most commonly confused conditions were infective and allergic conjunctivitis, blepharitis, and dry eyes. General practitioners assessed visual acuity in only 114 cases yet eight of the 15 patients seriously misdiagnosed had reduced acuity, an important diagnostic sign. CONCLUSIONS: Most ophthalmic disease seen in general practice does not require specialised equipment for diagnosis. Most cases of misdiagnosis have no serious consequences for the patient. Undergraduate and postgraduate training in ophthalmology should ensure that common conditions can be easily differentiated and more serious conditions identified and referred. PMID- 1445528 TI - Long-term weight control: the National Heart, Lung, and Blood Institute funded multimodal intervention study. PMID- 1445529 TI - U.S. health care dilemma. Some suggestions for solution. PMID- 1445530 TI - The sealants question. PMID- 1445531 TI - A new link in the brain's defenses. PMID- 1445532 TI - Cigarette smoking and small irregular opacities. PMID- 1445533 TI - [Hepatitis B and C, HIV-1 and HIV-2 infections in the gypsy population]. PMID- 1445534 TI - Benefits of violence prevention for African-American youth. PMID- 1445535 TI - Public health heresy. PMID- 1445536 TI - Hospital admission and benzodiazepine use. PMID- 1445537 TI - Site distribution of colorectal cancer. PMID- 1445538 TI - Gastrointestinal lipoma. PMID- 1445539 TI - Treatment of leg ulcers with allogeneic cultured keratinocyte-collagen dressings. PMID- 1445540 TI - Testing for fecal occult blood. PMID- 1445541 TI - Radiographic ordering agreement. PMID- 1445542 TI - Nursing perspective is critical part of NP graduate education. PMID- 1445543 TI - The impact of managed care on physicians. PMID- 1445544 TI - The evidence that a serotonergic mechanism plays an important role in cryogenic brain injury: are the results conclusive? PMID- 1445545 TI - International reference preparation for anti-measles serum. PMID- 1445546 TI - Hypoxia after dental anaesthesia. PMID- 1445547 TI - Irrational and pregnant. PMID- 1445548 TI - Opinions on responsibility toward wildlife. PMID- 1445549 TI - The value of secondary healing. PMID- 1445550 TI - Secondary healing after Mohs chemosurgery. PMID- 1445551 TI - Calcitonin gene-related peptide (CGRP) may significantly alleviate the vasospasm that often follows subarachnoid hemorrhage. PMID- 1445552 TI - Use of fibrin glue for partial nephrectomy. PMID- 1445553 TI - Umbilical artery flow velocity after vibratory acoustic stimulation. PMID- 1445554 TI - Predicting difficult intubation. PMID- 1445555 TI - Timing of surgery in congenital diaphragmatic hernia. PMID- 1445556 TI - Endoscopic transanal resection of large villous tumours of the rectum. PMID- 1445557 TI - 'The comparative strengths of commercial glass ionomer cements with and without metal additions'. PMID- 1445558 TI - Electrocoagulation in intrameatal warts. PMID- 1445559 TI - Antimicrobial prophylaxis in gynecologic and obstetric surgery. PMID- 1445560 TI - Group C streptococci: a current view. PMID- 1445561 TI - Ethical problems in genetic linkage studies. PMID- 1445562 TI - Physician ownership/referral arrangements. PMID- 1445563 TI - Diagnostic coronary arteriography. PMID- 1445564 TI - Caudate hyperdensities. PMID- 1445565 TI - Small sac size as a predictor of poor fetal outcome. PMID- 1445566 TI - Implantation of the tongue and floor of mouth--what factors really do contribute to necrosis? PMID- 1445567 TI - Re: Which dressing for split-thickness skin graft donor sites? PMID- 1445568 TI - Nucleotide sequence analysis and serologic characterization of the Mycobacterium intracellulare homologue of the Mycobacterium tuberculosis 19 kDa antigen. AB - Disseminated Mycobacterium avium/Mycobacterium intracellulare complex (MAC) disease is a frequent complication in patients with the acquired immune deficiency syndrome (AIDS). In this report, we present the nucleotide sequence of the M. intracellulare MI22 gene. Computer sequence comparisons reveal that the MI22 gene, which encodes a serologically active protein, has 78% DNA sequence identity and 77% protein sequence identity with the seroreactive 19 kDa Mycobacterium tuberculosis lipoprotein antigen. Southern blot hybridizations indicate that an MI22 gene probe binds similar-sized restriction fragments in M. tuberculosis and M. intracellular genomic DNA. In addition, immunoblot analyses demonstrate that MI22 is recognized by sera from tuberculosis patients. These data further support the existence of 19 kDa MAC and M. tuberculosis protein homologues. Phase partitioning experiments and the presence of a consensus lipid modification site in the deduced MI22 protein sequence strongly suggest that M122 is also a lipoprotein. Comparative analyses of these mycobacterial antigenic homologues may provide the basis for the design of species-specific diagnostic reagents. PMID- 1445569 TI - Take two spider webs & call me in the morning. Southern folk medicine. PMID- 1445570 TI - Transdifferentiation of macrophages into fibroblasts as a result of Schistosoma mansoni infection. AB - The possibility of transdifferentiation of macrophages into fibroblasts which could be at the origin of fibrotic tissue in schistosome-infected mice was studied using immunocytochemical techniques. Macrophage cell samples extracted from the peritoneal cavity of schistosome-infected mice were fractionated on a Percoll gradient. The cultures were purified by treatment with a trypsin solution to eliminate any fibroblasts possibly collected along with the macrophages. Immunocytochemical methods were then used to characterize the cells at different points in time. The fibroblastic property of the morphologically transformed cells was confirmed by their positive labeling with the anti-procollagen antibody. However, these cells still possessed the mac-1 and mac-2 antigens which characterize the monomacrophage line. PMID- 1445571 TI - ECT and delirium in Parkinson's disease. PMID- 1445572 TI - For and against Eusol. PMID- 1445573 TI - MRC trial of treating hypertension in older adults. PMID- 1445574 TI - Altitude induced illness. PMID- 1445576 TI - Best interests. PMID- 1445575 TI - House dust mite avoidance--the right way to go forward. PMID- 1445577 TI - Clozapine treatment of polydipsia: a prolactin connection? PMID- 1445578 TI - Compensation for injury--re-appraisal. PMID- 1445579 TI - Charges of sexual harassment at NIMH. PMID- 1445580 TI - SEC22 and SLY2 are identical. PMID- 1445581 TI - U.S. health care dilemma. PMID- 1445582 TI - Increase in kidney 8-hydroxydeoxyguanosine level with the progression of renal failure. PMID- 1445583 TI - Magnetic resonance imaging in the evaluation of knee injuries. PMID- 1445584 TI - Reliability of the slope of the end-systolic pressure-volume relationship as individual index of myocardial inotropic state. PMID- 1445585 TI - Doctors and control of major releases of chemicals. PMID- 1445586 TI - Hazards of transmission of HIV during invasive procedures. PMID- 1445587 TI - Organophosphorus compound poisoning. PMID- 1445588 TI - Flow cytometry in the study of the interaction between murine macrophages and the protozoan parasite Leishmania amazonensis. AB - A flow cytometry method was adapted to study interaction between murine macrophages and Leishmania amazonensis. Using this method it was possible to detect internalization of parasites through an increase in macrophage granularity (side scatter), with the latter indicating the presence of parasites inside parasitophorus vacuoles. A quenching technique was used to confirm the feasibility of the method and to distinguish between internalized and externally attached parasites. Experiments using fixed-labeled and killed-unlabeled parasites gave similar results, demonstrating that granularity was an adequate parameter in the study of parasite-macrophage interaction, when compared with labeling methods. Experiments that measured internalization using only the increase in macrophage granularity as an indicator showed that living L. amazonensis was internalized to a greater extent than killed-unlabeled parasites. This finding suggests that the parasite has an active role in the process of internalization. The 2 methods in combination, flow cytometry and labeling, can be used to study murine peritoneal cell-L. amazonensis interactions and to sort phagocytosing and nonphagocytosing subpopulations of macrophages for further studies. PMID- 1445589 TI - Hypophosphataemia, delirium and cardiac arrhythmia in anorexia nervosa. PMID- 1445590 TI - Surgical management of spastic diplegia. PMID- 1445591 TI - Alcohol and addictions. PMID- 1445592 TI - Manchonnage--an aortic anastomotic ePTFE sleeve. PMID- 1445593 TI - Ideal versus operational values for health care. PMID- 1445594 TI - Sleep disturbance in children with growth hormone deficiency. AB - We examined the effects of growth hormone (GH) deficiency on sleep development by performing all-night polysomnography in three female children with GH deficiency (GHD). The percentage of REM sleep seemed to be reduced before the treatment in 2 cases, and human GH (hGH) compensation slightly increased it. Submental twitch movements (mTMs), i.e., body movements during sleep localized in the submental muscle and lasting less than 0.5 seconds, were commonly disturbed in the three patients. Rapid eye movements in REM sleep (REMs) were reduced before the therapy in one case, this decrease being reversed on hGH compensation. REMs also seemed to increase after hGH treatment in the other two cases. Dopamines and cholinergic muscarinic agonists can cause GH release, while mTMs and REMs might be related to dopaminergic and cholinergic systems in the human brain. It is intriguing that GHD, and the disturbance of mTMs and REMs coexisted in children with GHD. Since a relatively poor social outcome in patients with GHD has been reported, even after hGH compensation, it is important to monitor their neurological development by means of evaluation of their sleep disturbance. PMID- 1445595 TI - Inhibition of rat tissue kallikrein gene family members by rat kallikrein-binding protein and alpha 1-proteinase inhibitor. AB - The regulation of tissue kallikrein activity by plasma serine proteinase inhibitors (serpins) was investigated by measuring the association rate constants of six tissue-kallikrein family members isolated from the rat submandibular gland, with rat kallikrein-binding protein (rKBP) and alpha 1-proteinase inhibitor (alpha 1-PI). Both these serpins inhibited kallikreins rK2, rK7, rK8, rK9 and rK10 with association rate constants in the 10(3)-10(4) M-1.s-1 range, whereas only 'true' tissue kallikrein rK1 was not susceptible to alpha 1-PI. This results in slow inhibition of rK1 by plasma serpins, which could explain why this kallikrein is the only member of the gene family identified so far that induces a transient decrease in blood pressure when injected in minute amounts into the circulation. PMID- 1445596 TI - Mother-to-infant transmission of human immunodeficiency virus by breast milk: presumed innocent or presumed guilty? AB - This article reviews the virological and epidemiological data available on transmission of the human immunodeficiency virus type 1 (HIV-1) by breast milk. Colostrum and breast milk are considered major modes of transmission for many animal retroviruses as well as human T-cell leukemia virus, mainly as the consequence of ingestion of infected cells. Several cases that strongly suggest transmission of HIV-1 through breast-feeding have now been reported. In addition, recent evidence suggests that postpartum HIV-1 seroconversion of a mother may be associated with a high risk of postnatal transmission to offspring via breast milk. Preventive measures such as pasteurization of breast milk have not been fully examined. While the World Health Organization continues to promote breast feeding in areas where no safe alternative exists, the Centers for Disease Control recommends that American women who are infected by HIV-1 not practice breast-feeding if a safe alternative is available. Large-scale, carefully controlled, prospective studies of the risk of HIV-1 infection associated with breast-feeding are of the utmost priority. Feasible and ethically acceptable feeding alternatives should be developed for countries where formula feeding has a strong negative effect on child morbidity and mortality. PMID- 1445597 TI - Clinical breast cancer, new developments in selection and endocrine treatment of patients. AB - Breast cancer is the most common malignant tumor among women, comprising an estimated 24% of all cancer cases and 18% of all cancer deaths. At least half of the patients with primary breast cancer will ultimately die by metastatic disease. The tumor characteristics, the natural course of the disease and the response to therapy vary strongly. A number of recently detected cell biological parameters such as oncogenes/suppressor genes, growth factors and secretory proteins are more or less important prognostic factors, because they influence the characteristics and behavior of a tumor with respect to metastatic pattern, extent of cellular differentiation, growth rate and response to treatment. However, there is no clear consensus how best to identify patients at high or low risk. In our experience c-myc amplification and pS2 protein are strong prognosticators for relapse rate, while in advanced disease (apart from a negative estrogen/progesterone receptor/pS2 status) amplification of HER2/neu is a good prognosticator for failure to endocrine therapy. In the diagnosis of breast cancer, in vivo imaging of tumors by labeled hormones or other factors also forms a new development which might have implications for treatment too. With respect to treatment both endocrine and chemotherapy can cure a minority of patients with micrometastases, but in patients with advanced disease only a prolongation of (progression-free) survival can be reached. Response rates decrease with increasing tumor load. In the past decade a number of interesting new endocrine agents has been developed such as new (pure) (anti)steroidal agents, vitamins, aromatase inhibitors, analogs of peptide hormones, prolactin inhibitors and growth factor antagonists. However, less is known on the (potential) interaction between hormones, chemotherapeutic agents, retinoids, cytokins, growth factor antagonists and irradiation. Rapid detection of new powerful combination therapies are needed to improve treatment results during the nineties. PMID- 1445598 TI - Pharmacological profile of TCV-309--a potent PAF antagonist. AB - TCV-309 potently and specifically inhibited the diverse biological actions of PAF such as platelet aggregation, hypotension, increased vascular permeability, bronchoconstriction and death. TCV-309 did not cause hemolysis or vascular irritation. TCV-309 showed beneficial effects on experimental endotoxic shock, anaphylactic shock and disseminated intravascular coagulation. PMID- 1445599 TI - Postantibiotic effect of amikacin and rifapentine against Mycobacterium avium complex. AB - Postantibiotic effect (PAE) has received little attention in the therapy of chronic intracellular infections, such as those caused by mycobacteria. Amikacin is active therapeutically against Mycobacterium avium complex, even though serum levels exceed the MIC for only a few hours. To determine the PAE of amikacin and rifapentine for M. avium, bacteria were exposed to concentrations of 1x, 4x, and 10x the MIC of each drug for up to 120 min. Regrowth of M. avium was compared with similarly diluted untreated cultures. No PAE was observed on an inoculum of 10(4) bacteria when rifapentine was used at 5x MIC, although a slight inhibition of growth was obtained at 10x MIC for 2 h. For amikacin, PAE was observed up to 48 h at concentrations of 4x and 8x MIC and exposure times of 30-120 min. A PAE of 22 h was seen with 10(7) cfu of M. avium during incubation for 30 min with amikacin at 4x MIC. These results show that amikacin, unlike rifapentine, has a long PAE against M. avium. PMID- 1445600 TI - Cloning of a subunit of yeast RNA polymerase II transcription factor b and CTD kinase. AB - Yeast RNA polymerase II initiation factor b copurifies with three polypeptides of 85, 73, and 50 kilodaltons and with a protein kinase that phosphorylates the carboxyl-terminal repeat domain (CTD) of the largest polymerase subunit. The gene that encodes the 73-kilodalton polypeptide, designated TFB1, was cloned and found to be essential for cell growth. The deduced protein sequence exhibits no similarity to those of protein kinases. However, the sequence is similar to that of the 62-kilodalton subunit of the HeLa transcription factor BFT2, suggesting that this factor is the human counterpart of yeast factor b. Immunoprecipitation experiments using antibodies to the TFB1 gene product demonstrate that the transcriptional and CTD kinase activities of factor b are closely associated with an oligomer of the three polypeptides. Photoaffinity labeling with 3'-O-(4 benzoyl)benzoyl-ATP (adenosine triphosphate) identified an ATP-binding site in the 85-kilodalton polypeptide, suggesting that the 85-kilodalton subunit contains the catalytic domain of the kinase. PMID- 1445601 TI - [European network of quality assurance in nursing]. PMID- 1445602 TI - [Nursing care of the elderly. Moral and ethical problems]. AB - The article deals with moral and ethical issues involved in nursing care of the elderly during their hospitalization. Nursing interventions resulted in iatrogenic complications as well as nursing dilemmas are also discussed. PMID- 1445603 TI - [Chronic hemodialysis treatment of patients older than 74 years. An epidemiological study in 16 renal units in Northern Greece]. AB - In a review of 1057 patients who started receiving chronic haemodialysis treatment during the last decade in 16 renal units of Northern Greece only 25 patients (2.36%) were found to be older than 74 years at start of haemodialysis treatment. The most common cardiovascular problems in these elderly patients were angina pectoris in 9 and difficulties in fistula creation in 10 patients. Arterial hypertension was present in 7 patients. The first year survival rate was 55.5%. Cardiovascular episodes were the commonest cause of death among the 14 patients who died. We conclude that during the last decade in Northern Greece, among patients receiving chronic haemodialysis treatment, only a few started treatment after the age of 74 years and although they had significant cardiac and vascular problems their first year survival rate was acceptable. PMID- 1445604 TI - [Effects of acute myocardial infarction on the patient's and the family's way of life]. AB - During the last decade, the relation between psychosocial factors and patient's personality in front of the risk of an acute myocardial infarction and his health progress after the infarction has fully been investigated. The patient's personality and a number of factors related to his job-carrier and family environment have been proved to be very important. The effect of patient's behaviour, educational level, social and psychological status in the progress of coronary heart disease have especially pointed out. The myocardial infarction is a serious disease which can alter the patient and his close family's way of life due to its financial among the other consequences. This influences the members of the family as an entity and alters their life in many ways. The present study aims to investigate how the myocardial infarction as an expected or unexpected event affects differently and at which degree the behaviour of patient's family. PMID- 1445606 TI - [Nursing care research on the evaluation of elderly patients]. AB - Research in nursing of elderly patients refers to the investigation of their special needs as well as the context and methods for this kind of care to be provided. Reports published on nursing needs are rare. Clinical nursing evaluation of elderly patients and relevant research studies are briefly reviewed. PMID- 1445605 TI - [Study of clean versus aseptic technique of tracheotomy care based on the level of pulmonary infection]. AB - The purpose of this research study was to determine whether the clean technique of tracheotomy care is the same, or more, secure from the aseptic, by testing the difference in the level of postoperative pulmonary infection between tracheotomized patients receiving aseptic and those receiving clean tracheotomy care. The sample consisted of 103 patients with tracheotomy (transient or permanent) from ENT or IC units of four big hospitals of Athens. The level of the patient's pulmonary infection was defined using the Weighted Level of Pulmonary Infection Tool, which was constructed especially for this research study. The data were analysed using the x2 statistical test, and the coefficients phi, Cramer's V and Kendall's, while, with the same statistics, the relationship between certain important external variables and the dependent variable was examined. The findings indicated that no statistically significant difference exists between clean and aseptic technique as to the level of pulmonary infection when used for tracheotomy postoperative care of tracheotomized patients. PMID- 1445607 TI - [The present status of interpleural analgesia]. AB - Since the introduction of interpleural administration of local anaesthetics by Kvalheim and Reiestad in 1984, this technique has been applied to treat postoperative pain after cholecystectomy, renal, thoracic and unilateral abdominal surgery. Other indications are pain control in patients who suffered multiple rib fractures and in patients with chronic pain due to pathological processes in the pancreas. Due to the fact that interpleural analgesia is considered a new anaesthetic procedure, a number of questions still have to be answered regarding the mechanism of action, the appropriate local anaesthetic solution to be employed and, most importantly, the benefit/risk ratio associated with this technique. The purpose of this review article is to give a detailed account of the knowledge and obtained clinical experiences present to date regarding interpleural analgesia, and to give a critical evaluation of this method. PMID- 1445608 TI - [Anaphylactoid reactions to muscle relaxants]. AB - Anaphylactoid (i. e. anaphylactic-like) reactions have been estimated to occur in between one in 600 and one in 1,000 general anaesthesias. Two thirds of these reactions are caused by neuromuscular blocking drugs used during anaesthesia. An anaphylactoid potential is inherent in all muscle relaxants, albeit to a varied extent, reflecting an obligatory feature of their molecular structure (quaternary ammonium groups) and common physicochemical characteristics. Hence, also newer relaxants are not void of anaphylactoid risk. In Britain, the recent availability of drug-specific radioallergosorbent tests (RAST) has initiated much controversy on preanaesthetic antibody screening and possible medicolegal consequences. Since every anaesthetist must expect to be faced with such an unforeseen and occasionally life-threatening reaction, the characteristic clinical manifestations, basic therapeutic strategies and current opinion on underlying pathophysiological mechanisms are summarized in this review article. Based on the recommendations of the British National Adverse Anaesthetic Reaction Advisory Service (NAARAS), essential diagnostic procedures during and after anaphylactoid events are discussed. Finally, prophylactic precautions including the preoperative administration of H1- and H2-antihistamines are recommended. PMID- 1445609 TI - [Nifedipine prolongs a neuromuscular blockade caused by atracurium]. AB - Calcium entry blockers are now widely employed in the treatment of cardiovascular diseases and perioperative hypertension. In patients with coronary heart disease nifedipine therapy should be continued perioperatively to avoid coronary artery spasm. Animal experiments have demonstrated that calcium entry blockers potentiate the neuromuscular blockade induced by nondepolarizing blocking agents. In patients, an atracurium-induced neuromuscular depression is prolonged by intravenous nifedipine. In this prospective clinical study we evaluated the effect of chronic oral nifedipine therapy on the duration of neuromuscular block by atracurium. Sixty patients anaesthetized with isoflurane in nitrous oxide/oxygen were recruited for this study. Thirty of these were on chronic oral nifedipine therapy and received their normal morning dose before premedication. The control consisted of 30 patients of similar age and status but not taking any calcium entry blockers. Monitoring included noninvasive blood pressure, heart rate, pharyngeal temperature, physical breathing parameters and neuromuscular transmission with a Datex Relaxograph TM ("train of four"-principle). After inducing hypnosis 0.5 mg/kg atracurium were administered for muscular relaxation. The duration of block from administration of the relaxant to recovery of first twitch height (T1) to 25% of control twitch height was registered as duration of initial block. When T1 reached 25% a repetition dose of 0.2 mg/kg atracurium was injected. The time till recovery of T1 to 25% was recorded as the duration of the repetition dose. Results were compared using Student's t-test for unpaired data. There was a significant prolongation of the duration of initial block from 38 min +/- 10 min in the control group to 46 min +/- 8 min in the therapy group (P < 0.01). The duration of the repetition dose rose from 30 min +/- 8 min in the control group to 38 min +/- 7 min in the therapy group (P < 0.001). Daily nifedipine doses varied from 10 mg in the morning to 40 mg divided into single doses with no influence on the prolongation of neuromuscular block. Our results confirm previous assumptions of synergistic effects of nifedipine and neuromuscular blocking drugs in patients. Chronic oral nifedipine therapy potentiates neuromuscular blockade by atracurium as does nifedipine intravenously. This effect should be considered in the treatment of cardiovascular diseases with nifedipine in the perioperative period. PMID- 1445610 TI - Pyrazolo[3,4-d][1,2,3]triazole-1-carboxamides and 5-alkylaminopyrazolo[3,4 d]oxazoles: synthesis and evaluation of the in vitro antifungal activity. AB - A series of N-alkyl-N'-(4-diazo-5-pyrazolyl)-ureas (4) was thermally and photochemically converted into pyrazolo [3,4-d][1,2,3]triazole derivatives (5,6) and 5-alkylaminopyrazolo[3,4-d]oxazoles (7) respectively. The products were tested for in vitro antifungal activity against Fusarium culmorum, Botrytis cinerea, Phoma betae, Pythium ultimum, Sclerotinia minor and Rhizoctonia solani. The MIC and ED50 values of compound (6) against some of the test fungi were comparable to those of the reference fungicides iprodione and mancozeb. PMID- 1445611 TI - Pyrimidoacridine derivatives as potential antitumor agents. AB - A series of some N-alkylaminoalkyl derivatives of pyrimido[5,6,1-d,e]acridine 1,3,7-trione (3) was synthesized as new potential antitumor drugs, starting from the suitable 9,10-dihydro-9-oxo-4-acridinecarboxamides and using phosgene as cyclizing agent. 1-(9,10-dihydro-9-oxo-4-acridinecarbonyl)-3-alkyl-2-imidazolido nes were also obtained as side products. The final products 3 and some carboxamides were tested "in vitro" against L 1210 leukemia and "in vivo" against P388 leukemia. Of the tested compounds, one is active "in vivo", another shows significant cytotoxic activity "in vitro", but is inactive or toxic "in vivo". PMID- 1445612 TI - Studies on anti-Candida agents with a pyrrole moiety. Synthesis and microbiological activity of some [(1-alkyl),(1-aryl) and (1-benzyl)-5-aryl-3 carboxamido-2-methyl]pyrrole derivatives. AB - The synthesis of some [(1-alkyl),(1-aryl) and (1-benzyl)-5-aryl-3-carboxamido-2 methyl]pyrrole derivatives is reported. Their activity against Candida strains has been assessed and the structure-activity relationships for these compounds are discussed. PMID- 1445613 TI - Synthesis and antimycobacterial activity of some 2-pyridinecarboxyamidrazone derivatives. AB - A series of N1-aryliden-2-pyridincarboxyamidrazone derivatives was prepared. Some of the synthesized compounds showed interesting in vitro antimycobacterial activity against some strains of Mycobacterium and clinical isolates of Mycobacterium tuberculosis. PMID- 1445614 TI - Simultaneous determination of amiodarone and desethylamiodarone in human plasma by high performance liquid chromatography. AB - A rapid, sensitive and specific reversed phase HPLC method for the simultaneous assay of amiodarone and its major metabolite desethylamiodarone in human serum has been developed. This method is suitable for pharmacokinetic studies and for monitoring of the drug and metabolite concentrations in serum of patients on both short and long-term therapy with amiodarone. PMID- 1445615 TI - Stability study of cloxacillin in an oily suspension, by high performance liquid chromatography. AB - A high performance liquid chromatography method, using spectrophotometric detection (254 nm) has been developed for the analysis of cloxacillin in an oily suspension. Analysis was performed by isocratic elution with 0.02M potassium dihydrogen phosphate solution, methanol, 50/50 (V/V). The method was specific, linear, accurate (99.8 +/- 1.4%) and precise (less than 1.0%). A stability study of cloxacillin in the formulation, showed that about 10% degradation occurred for 6 months storage at room temperature, when lyophilized sodium cloxacillin was used. On the contrary, when sodium cloxacillin obtained by precipitation from non aqueous solvent was used, about 6% degradation appeared in the drug for 3 years storage in the same conditions. PMID- 1445616 TI - HPLC detection of thioperamide from biological samples and its determination in rat blood and brain after systemic administration. AB - Thioperamide is a potent and selective antagonist on histamine H3 receptors. A method for its isolation and quantitation by HPLC from rat plasma and brain samples has been developed. Using this technique, thioperamide concentrations in rat plasma and brain were measured after systemic administration, in order to evaluate its persistence in blood and its ability to cross the blood-brain barrier. We observed that, at a dose of 60 mg/Kg, thioperamide undergoes a slow elimination from plasma, with a half-life of 10 hours, and can readily cross the blood-brain barrier. PMID- 1445617 TI - Simultaneous quantitative determination of calcium leucovorin and parabens in lyophilized ampoules by derivative spectroscopy. AB - A simple and rapid procedure for quantitation of Calcium Leucovorin and parabens simultaneously in lyophilized ampoules formulation by "zero crossing" first-order derivative spectroscopy was developed. The ampoules content was dissolved in a mixture water/ethanol (50/50) and first-derivative spectra were recorded. The absolute values of the derivative at 312 nm for the determination of Calcium Leucovorin and between 244 and 246 nm for the determination of parabens were measured. The method is linear, quantitative and reproducible. PMID- 1445618 TI - Researches on psychotropic agents. IV. Synthesis and neuropsychopharmacological effects of 1,3,4,14 b-tetrahydro-10-methyl-2H,10H- pyrazino[2,1-d] pyrrolo[1,2 b][1,2,5]benzotriazepine and its derivatives. AB - The synthesis and neuropsychopharmacological properties of new 1,3,4,14b tetrahydro-2H,10H-pyrazino [2,1-d] pyrrolo [1,2-b] [1,2,5] benzotriazepine derivatives related to antidepressant agent aptazepine are reported. The new derivatives displayed sedative-miorelaxant activity in mice, but no significant antagonist effect on clonidine blockade of phenylquinone-induced abdominal constriction. Among test compounds 4a, 4l and 4n showed high antinociceptive effect on the hot-plate test and compound 4e protected from death and convulsion all the electroshocked animals. PMID- 1445619 TI - Linking cellular injury to gene expression and human proliferative disorders: examples with the PDGF genes. PMID- 1445620 TI - Mutational analysis of a dominant oncogene (c-Ki-ras-2) and a tumor suppressor gene (p53) in hamster lung tumorigenesis. AB - In human lung cancers, alterations of both a dominant oncogene (ras) and a tumor suppressor gene (p53) have been identified. Polymerase chain reaction (PCR) analysis of mRNA was used to amplify the c-Ki-ras-2 and p53 genes from Syrian golden hamsters. The PCR products were confirmed by predicted-size analysis, probing with nonradioactive (biotin-labeled) oligonucleotides, and direct sequencing. Lung tumors were produced in hamsters by repeated injections of 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Of six tumors examined, three (50%) had mutations in codon 12 of Ki-ras. Examination of the conserved regions of p53 revealed no mutations. We conclude that NNK-induced carcinogenesis in the hamster results in characteristic alterations of Ki-ras but may not necessarily involve the p53 gene. PMID- 1445621 TI - Role of activator protein-1 and methylation function in 12-O-tetradecanoylphorbol 13-acetate--mediated inhibition of differentiation of Friend erythroleukemia cells. AB - Friend erythroleukemia cells (FELCs) differentiate after hexamethylene-bis acetamide treatment. This differentiation is characterized by an increase in beta globin gene expression that is followed by appearance of the hemoglobin. Phorbol ester tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibit differentiation of TPA-sensitive cells but not TPA-resistant cells. We have shown that the increase in beta-globin expression is inhibited by TPA in a TPA-sensitive clone but not in a TPA-resistant clone. To study the molecular mechanisms of regulation of gene expression by TPA, we examined the possible involvement of gene methylation and the TPA-responsive element (TRE). Both clones showed similar patterns of methylation around the beta-globin gene. Moreover, TPA induced TRE binding and TRE enhancer activity were similar in both variants. These results suggest that the TPA inhibition of induced differentiation may not be explained by regulation of the methylation state. The activator protein-1 also does not play a crucial role in the sensitivity of FELCs to TPA. PMID- 1445622 TI - 12-O-tetradecanoylphorbol-13-acetate--induced levels of AP-1 proteins: a 46-kDa protein immunoprecipitated by anti-fra-1 and induced in promotion-resistant but not promotion-sensitive JB6 cells. AB - Neoplastic transformation and transcriptional activation by activator protein-1 (AP-1) complex are stimulated by tumor-promoting agents in promotion-sensitive (P+) but not promotion-resistant (P-) mouse epidermal JB6 cells in culture. This implicates AP-1 as a specific regulator of signal transduction pathways in the promotion phase of neoplastic transformation. We therefore hypothesized that the defective P- responsiveness may be due to limiting levels of AP-1 protein components in those cells. In this investigation, steady-state levels of AP-1 protein components were measured by immunoprecipitating proteins from 12-O tetradecanoylphorbol-13-acetate (TPA)-treated P+ and P- cells to discern what may limit the AP-1 response. Whereas the AP-1 proteins junB, junD, and fosB did not show differential basal or TPA-inducible levels in P+ and P- cells, a 46-kDa species precipitated by anti-fra-1 antibody was TPA-inducible in P- cells but not in P+ cells, and c-jun protein was present at higher levels in TPA-treated and untreated P+ cells than in P- cells. These data raise the possibility that the 46 kDa fra-1-related protein may be a negative modulator of AP-1 activity and suggest that elevated levels of this 46-kDa species and limiting levels of c-jun may significantly impair AP-1 function or transformation response in P- cells or both. PMID- 1445623 TI - Simplified dosing and monitoring of vancomycin for the burn care clinician. AB - Vancomycin has excellent activity against Gram-positive bacteria and is often selected for use in the infected burn patient. Because of multiple-compartment pharmacokinetics, vancomycin serum concentrations can decrease dramatically in a short time period following the end of an intravenous infusion. This accounts for the widely divergent recommendations for serum vancomycin peak concentrations, e.g. from 15 mg/l up to 80 mg/l, when the time for blood sampling following the end of intravenous infusion is different. It is in general not necessary to monitor vancomycin peak concentrations, not only because its toxic potential is overrated but also because potential toxicity and therapeutic efficacy are correlated with trough concentrations. Post-distribution 'peak' concentrations are generally only useful for determining the optimal dosing interval for patients with impaired renal function. A dosing and monitoring paradigm for vancomycin therapy in burned adults has been devised for burn care clinicians. It provides suggested dose and dosing intervals based on body weight and creatinine clearance, with specific recommendations for regimen modification based upon the results of trough serum concentration determinations. PMID- 1445624 TI - Dynamic balance changes between elastase and antiprotease in the early stages after smoke inhalation injury. AB - Following the use of a rabbit smoke inhalation injury model established in this institute, there were marked reductions in elastase activities in neutrophils and alveolar macrophages; rapid increases in elastase activity in broncho-alveolar lavage fluid (BALF); reductions of serum trypsin inhibitory capacity; a decrease of Pao2 and an increase of PaCO2, and marked increases of lung water volume. Significant correlations were found between the increased extravascular lung water content and the rising elastase activity in BALF. It seems probable that the imbalance between elastase and antiprotease played an important role in the development of acute lung injury after smoke inhalation. PMID- 1445625 TI - Predicting survival in burned patients. AB - Data pertaining to 562 consecutive admissions for burn treatment were analysed to identify factors related to survival. Besides socioeconomic, demographic and burn related variables, three indices to measure burn severity, were proposed and evaluated with the help of multiple regression and discriminant analyses. The results of multiple regression analysis showed that one of the proposed indices, total burned surface (TBS), based on presence or absence of burn injury on 11 different body sites, turned out to be the best single predictor of survival. TBS alone accounted for 64.5 per cent of the total variance in survival variable. Combined use of TBS with type and severity of burn, age, sex, etc. did not appreciably raise the value of R2. The results of the discriminant analysis yielded a cut-off point of 20 TBS score which provided maximum separation between survivors and fatalities. Using this cut-off point (20 per cent) the TBS index provided the correct prediction of the eventual survival status in about 93 per cent of 562 patients. This cut-off point score of 20 was cross-validated on an independent sample of 924 cases. The prediction in 79 per cent of patients could be made correctly. PMID- 1445626 TI - Cutaneous copper and zinc losses in burns. AB - To measure the exudative cutaneous copper (Cu) and zinc (Zn) losses in burns, 10 patients, aged 36 +/- 9 years (mean +/- s.d.) with burns covering 33 +/- 10 per cent of the total body surface area, were studied from the first postburn day (D1) until D7. All intakes and losses were analysed for Cu, Zn and nitrogen (N) content. Cutaneous losses were extracted from textiles surrounding the patients. Urinary excretions were 0.12 +/- 0.06mg/24h for Cu, 0.9 +/- 0.6mg/24h for Zn, and 14.1 +/- 4.4g/24h for N. Mean daily exudative losses through wound seepage from D1 to D7 were 4.7 +/- 2.1mg/24h for Cu, 27.1 +/- 14.4mg/24h for Zn, and 8.7 +/- 3.8g/24h for N. The cumulated mean losses over 7 days were 37mg for Cu, and 212mg for Zn, representing respectively 20-40 per cent and 5-10 per cent of normal body content. Serum Cu and Zn levels were strongly depressed. The urinary Cu/N ratios correlated with clinical improvement. We conclude that the exudative Cu and Zn losses during the first week postburn contribute significantly to the increased nutrient requirements in burns. PMID- 1445627 TI - Formation of gastrocnemius [3H]polyinositol phosphates in response to burn trauma. AB - The purpose of this report was to see if changes in polyinositol phosphates occurred with increasing percentage body surface area (% BSA) burn. Burn injury was applied to predefined areas of the dorsal and ventral skin surface of mice. After a 10-min stimulation period involving muscle twitch, polyinositol phosphate levels at 3 weeks postburn were measured by the incorporation of myo[2 3H]inositol with separation of the phosphates by anion-exchange chromatography. Analysis of variance was used for all statistical evaluations. In gastrocnemius muscle an increase (P < 0.001) occurred for levels of [3H]inositol, inositol-1, phosphate (I1P), and inositol-1,4,5-trisphosphate (I1,4,5P3) for the 50 per cent BSA burn group. However, levels of inositol-1;4,biphosphate (I1,4P2) decreased (P < 0.001). Positive correlations were found between [3H]inositol, I1P and IP3 and 50 per cent BSA burn. A negative correlation between I1,4P2 and percentage BSA burn was found. These data provide evidence that polyinositol phosphate metabolism in skeletal muscle was altered due to large burn size. PMID- 1445628 TI - Effect of chronic interleukin-2 treatment on RES phagocytic activity in the rat. AB - The effect of chronic interleukin-2 (IL-2) injection upon reticuloendothelial system (RES) function in the rat has been determined. Seven-day treatments with two doses of human recombinant IL-2 resulted in a dramatic reduction in the phagocytic uptake of the liver and spleen, while increasing the weight of both organs. There were dramatic histological changes in the intestine, liver and spleen as well. These results suggest that the chronic use of IL-2 can result in hepatic dysfunction, which is associated with altered RES phagocytic function. PMID- 1445629 TI - Microskin grafting of rabbit skin wounds with Biobrane overlay. AB - Biobrane was used to overlay micrografts and the wound using the microskin grafting technique with an expansion ratio of 10:1 in 16 rabbits. The rabbits were divided randomly into four groups, with four rabbits in each group, for evaluating the wound conditions on days 7, 10, 12 and 14. Histological examination of the removed Biobrane showed a variable degree of entrapment of inflammatory cells within the nylon fabric. Biobrane adhered well to the wounds although many wrinkles containing fluid accumulations were noted on day 7. By 10, 12 and 14 days all the wounds become dry and their Biobrane adhered completely. Histological examination of the grafted wound on day 7 showed active proliferation and spread of micrografts. In the later groups, the neoepidermis increased in thickness and differentiated into skin with a normal texture. On day 10, the wounds were almost completely resurfaced with neoepithelium. The growth of these grafts progressed smoothly as the adherent Biobrane was kept on the wound for 12 or 14 days. In these animal studies, the overlain Biobrane provided favourable conditions for the successful growth of micrografts. PMID- 1445630 TI - Fibrin glue in the treatment of dorsal hand burns. AB - This paper analyses two groups of patients with only dorsal hand burns: groups I contains patients with a total of 15 burned hands and group II patients with 12 hand burns. The patients in group I were all treated by full sheet skin grafts using a two-component fibrin glue. Patients in group II underwent the traditional operative treatment without fibrin glue and the same postoperative physical therapy programme. After follow-up periods of 6-11 months (group I) and 12-21 months (group II), we investigated in both groups, grip strength, key pinch, mobility, two-point discrimination and with the Semmes-Weinstein monofilaments. Our results prove that after the respective follow-up periods group I patients developed far better results for two-point discrimination, touch recognition and mobility. PMID- 1445631 TI - Increased survival rate in patients with massive burns. AB - A review of 113 patients with massive burns treated in our centre from 1970 to 1989 is presented. There were 57 adults patients with massive burns (> or = 50 per cent TBSA) in 1980-89 who were compared with 56 patients with similar massive burns in the period between 1970 and 1979. The results show a significant improvement (P < 0.01) in survival rate of the more recent patients. The increased survival rate is attributed to improvements in the early treatment of inhalation injury, sepsis and multiorgan failure. PMID- 1445632 TI - Wound healing of burns in rats treated with a new amino acid copolymer membrane. AB - A new amino acid copolymer (leucine + methylglutamate) membrane which is moderately permeable to water vapour, impermeable to bacteria, non-biodegradable and stable, has been developed as a burn wound covering. In an experimental model in the rat, excised burn lesions were covered either with the membrane or with conventional petrolatum-impregnated gauze. Morphometric analyses and histological investigations performed on days 7, 14, 21 and 42, suggested a significantly increased rate of healing for wounds covered with the polymeric membrane as compared with those covered with impregnated gauze. No wound dessication, fluid retention or exudate was observed under the membrane due to its moderate permeability to water vapour. The wounds covered with impregnated gauze also showed a marked inflammatory response in the granulation tissue, which remained even at day 42. This appearance was very different from a normal dermis or a polymeric membrane treated dermis. PMID- 1445633 TI - A technique of haemostasis of the extremities after debridement of burn wounds. AB - A technique used to achieve prompt haemostasis in burned wounds of the extremities is described. After tangential debridement using a tourniquet, thrombin solution (1000 units in 1 ml of saline solution) is applied on the entire wound. Immediately after removing the tourniquet; the wound is tightly wrapped with a thin plastic film and a pressure bandage over the entire wound. The pressure bandage is kept on for approximately 10 min after removing the tourniquet. With this procedure, haemostasis of the capillary oozing can be promptly and completely achieved. Furthermore, arterial and venous haemostasis can also be achieved, with clots present at the arterial and venous haemorrhagic points. As these clots can be removed easily, ligation or electrocoagulation is necessary. This technique is especially useful for haemostasis in a wound of the extremity after tangential excision leading to decreasing blood loss. PMID- 1445634 TI - Burns as a result of domestic accidents and their prevention. AB - Over a 1-year period (October 1990 to October 1991), 100 patients with burns due to domestic accidents have been admitted to our Burn Unit. The total number of burn admissions was 238. There is a relative abundance of data in the burn literature, clearly depicting local characteristics and peculiarities in different countries or societies. Our purpose is to present some statistical, epidemiological and socioeconomic data from Greek society, as well as to compare data from other countries. PMID- 1445635 TI - Experience of a chemical burn due to 3,5-dichloro 2,4,6-trifluoropyridine. AB - An example is reported of a burn caused by cutaneous exposure to 3,5-dichloro 2,4,6-trifluoropyridine (DCTFP) involving 25 per cent of the body surface. A striking feature was the development of the appearance of the burn over the first 72h postinjury. Healing was nevertheless spontaneous. The management of the injury is discussed. PMID- 1445636 TI - Burns of the skull with underlying intracranial meningioma. AB - A 68-year-old white-skinned male fell head first into a fireplace while having a seizure. Extensive burns of the skull were sustained requiring removal of the necrotic bone. The patient had an underlying meningioma. Healing of the skull was obtained using a latissimus dorsi flap. After the scalp was completely healed, the meningioma was successfully resected with significant improvement in the patient's mental function. PMID- 1445637 TI - Trapezius myocutaneous flap for reconstruction of a large scalp defect following the excision of postburn scar carcinoma (Marjolin's ulcer). AB - The successful use of a trapezius myocutaneous flap to cover a large scalp defect resulting from the excision of a postburn Marjolin's ulcer is described. The exposed dura was covered with a good functional and cosmetic result. PMID- 1445638 TI - Accidental pressure cooker lid blow-out. PMID- 1445639 TI - [Resources and quality of Chinese drug guipi]. PMID- 1445640 TI - [Macrological identification of Chinese drug dangshen (radix Codonopsis)]. AB - Macrological characters of 17 reference crude drugs from Codonopsis and Campanumoea were observed. Identification of 110 samples collected from 18 provinces of China indicated that more than 70 percent of the commercial Dangshen is derived from Codonopsis pilosula. PMID- 1445641 TI - [Identification of Chinese traditional drug baijiangcao by ultraviolet spectrum]. PMID- 1445642 TI - [Growth regularities of yujin (Curcuma longa L.)]. AB - Based on the characteristics of leaf, root and tuber growth as well as dry matter accumulation, the ontogeny of Yujin is divided into 4 stages. The growth and correlation among the leaf, root and tuber as well as accumulation of essential oils and curcumins have also been studied. PMID- 1445643 TI - [Determination of magnolol and honokiol in different processed samples of houpo by HPLC method]. AB - HPLC was applied to determine and compare 17 samples of Houpo processed in different ways: sauted with ginger juice, dipped with ginger juice, boiled with ginger juice, and so on. The results provide a scientific basis for screening the best processing technology of Houpo. PMID- 1445644 TI - [Thin layer chromatography for identification of 9 species of traditional Chinese medicine in baihe gujin tang granules]. AB - Baihe Gujin Tang granules are mainly composed of nine species of traditional Chinese medicine and other admixtures, so the composition is very complex. In order to confirm the presence of each traditional Chinese medicine in the preparation, a thin layer chromatographic method was developed successfully for analysis of Scrophulariae, Platycodon, Paeoniae and Glycyrrhizae. PMID- 1445645 TI - [Granule-making technology for preparing luohanguo chrysanthemum granule medicine with orthogonal design]. AB - L9 (3(4)) orthogonal design was adopted to inspect the consumption of white sugar, water and ethanol and the duration of raw material mixing in relation to the granule-attaining rate in preparing Luohanguo-Chrysanthemum granule medicine. The result shows that with a consumption of 170 kg of white sugar, 6000 ml of water and 800 ml of ethanol and a duration of 8 minutes, the granule attaining rate reaches about 80%. PMID- 1445646 TI - [Chemical constituents of Lysionotus]. PMID- 1445647 TI - [Chemical constituents of Actinidia kolomikta (Rupr. et Maxim.) Planch]. AB - Two crystalline components I and II were isolated from the roots of Actinidia kolomikta. I was identified as delta 7-stigmasterol and II was named alpha kolomiktriose and elucidated as 2, 3-di-0-beta-D-galactopyranosyl-alpha-D galactopyranose on the basis of spectral data (13C NMR, 1H NMR, IR and EI-MS). PMID- 1445648 TI - [Chemical components of the leaves of Pistacia Chinensis Bge]. AB - Six compounds have been isolated from the leaves of Pistacia chinensis, a species of Anacardiaceae family. Their structures were identified on the basis of UV, IR, NMR, and MS as gallic acid, m-digallic acid, quercetin, 6-0-galloyl arbutin quercitrin and quercetin-3-0(6''-galloyl)-beta-D-glucosides. PMID- 1445649 TI - [Pharmacokinetics of sinomenine by HPLC]. AB - Pharmacokinetics of sinomenine in rabbit was studied by reverse-phase HPLC method. After i.v. injection of 20 mg/kg of sinomenine to rabbits, the pharmacokinetic characteristics were found to fit a two-compartment open model. PMID- 1445650 TI - [The effects of dachengqi decoction, shaogan decoction, emodin and sennoside on the histamine level of intestinal mucosa in intestinally obstructed rats]. AB - The experimental intestinal obstruction model was made by partly ligating the ileum in rat. The histamine levels of obstruction groups (8.14 +/- 2.28 micrograms/g) were obviously lower than those of control groups (P < 0.01). After administration of Dachengqi decoction, Shaogan decoction, emodin and sennoside, the levels of histamine were significantly higher than those of obstruction groups, but there were no significant differences as compared with control groups. PMID- 1445651 TI - [Hypoglycemic effect of fructus Ligustri Lucidi]. AB - The decoction of Fructus Ligustri Lucidi (FLL) 15.30 g/kg ig for 10 days significantly decreased the blood glucose level in normal mice. FLL 30 g/kg before or after the treatment of alloxan also decreased the blood glucose level in alloxan diabetic mice. The elevation of blood glucose level induced by adrenaline or glucose was antagonized by FLL. PMID- 1445652 TI - [A survey of adverse effects of Chinese herbal drugs in China, 1915-1990]. PMID- 1445653 TI - A new role for the cerebellum in cognitive operations. AB - Over the last 2 centuries, the predominant view of the cerebellum has been that it is part of a motor control system. Evidence is now presented that the neocerebellum, the evolutionarily newest region of the cerebellum, may also be involved in a key mental operation: the voluntary shift of selective attention between sensory modalities. It is theorized that this newly recognized function may operate via previously described sensory modulation properties of the cerebellum and its many connections with areas known to be important for selective attention, such as the pulvinar, the superior colliculus, and the parietal and frontal cortices. PMID- 1445654 TI - Cerebellar stimulation as an unconditioned stimulus in classical conditioning. AB - Rabbits were implanted with chronic stimulating electrodes in white matter underlying lobule HVI of the cerebellar cortex. Stimulation elicited movements of the face or neck and, when paired with a tone conditioned stimulus (CS), produced learning comparable to that seen with peripheral unconditioned stimuli (USs). CS alone trials produced extinction. Reinstatement of paired trials produced reacquisition with savings. Additional groups received either explicitly or randomly unpaired CS-US trials before paired conditioning. Low-frequency responding during these sessions indicated that the paired training results were associative and not due to pseudoconditioning or sensitization. Explicitly unpaired sessions retarded learning on subsequent paired trials compared with groups that received either randomly unpaired or no CS-US preexposure. These results are interpreted in terms of the role of the cerebellum and associated pathways in classical conditioning of motor responses. PMID- 1445655 TI - Hippocampus, fimbria-fornix, amygdala, and memory: object discriminations in rats. AB - Rats with lesions of the fimbria-fornix, hippocampus, or hippocampus and amygdala were tested in object discriminations commonly used with monkeys. Two 1-pair object discriminations were learned preoperatively and tested postoperatively. Additional postoperative testing included acquisition of a third 1-pair object discrimination, an 8-pair concurrent object discrimination, and spatial alternation. All lesions impaired performance in the 8-pair object discrimination and in spatial alternation but not in the 1-pair object discriminations. Data from this study and from previous studies indicate that the hippocampus in both rats and monkeys has an important role in the mnemonic processes required for concurrent object discriminations and that variations of the procedure for concurrent object discriminations can be an effective tool for investigating hippocampal function. PMID- 1445656 TI - Complementary roles of the orbital prefrontal cortex and the perirhinal entorhinal cortices in an odor-guided delayed-nonmatching-to-sample task. AB - Continuing efforts toward designing odor-guided tasks for rats that are similar in memory demands to tasks used typically with primates have resulted in the development of a continuous delayed-nonmatching-to-sample (cDNM) task that is guided by olfactory stimuli. The results indicate that normal subjects acquire the cDNM task rapidly and that subsequent performance deteriorates with increases in memory delay or interitem interference. Moreover, different aspects of cDNM performance were shown to be differentially sensitive to selective lesions of the orbitofrontal and parahippocampal areas. Orbitofrontal cortex lesions disproportionately impaired cDNM acquisition; delay performance was impaired only under conditions of elevated levels of interitem interference. Combined perirhinal and entorhinal cortical lesions had no effect on cDNM acquisition but impaired cDNM performance at longer delays across all levels of interference. Fornix lesions did not impair either acquisition of cDNM or subsequent performance across long delays and increased interference. This pattern of impaired and spared capacities is similar to that observed in monkeys after lesions of analogous areas and is consistent with the notion that the prefrontal cortical system contributes preferentially to learning general task "rules" such as the nonmatching rule that is inherent in cDNM, whereas the perirhinal and entorhinal cortical areas are involved in the intermediate-term maintenance of memories for specific information. PMID- 1445657 TI - Increased training in an aversively motivated task attenuates the memory impairing effects of posttraining N-methyl-D-aspartate-induced amygdala lesions. AB - This study was designed to examine the effect of variations in the amount of preoperative training on the retention deficit produced by posttraining lesions of the amygdaloid complex (AC). Rats received 1, 10, or 20 training trials in a footshock-motivated escape task 7 days before receiving N-methyl-D-aspartate lesions of the AC. Inhibitory avoidance retention performance, which was measured 4 days postoperatively, indicated that increased training improved retention in AC-lesioned animals as well as in control animals. The retention performance of AC-lesioned animals was impaired when compared with that of controls; however, the impairment was partially attenuated by increased preoperative training. The finding that AC-lesioned animals displayed greater locomotor activity on the retention test compared with nonlesioned controls suggests that the increased activity may have contributed to the impaired inhibitory avoidance retention performance. Two days after the retention test, some of the AC-lesioned animals were subsequently trained on a continuous multiple-trial inhibitory avoidance response in the same apparatus. AC lesions did not block acquisition or retention of the task. These findings suggest that the amygdala may not be a critical site for the permanent changes mediating stimulus-affect associations based on extensive training. PMID- 1445658 TI - Effects of unilateral parietal lesions on spatial localization in the rat. AB - In the first of two experiments, rats with left or right parietal lesions and controls were tested in place and landmark navigation in the water maize. Right parietal lesions resulted in deficits in both tasks, but especially landmark navigation. Lateralized effects appeared mainly in latency to find the platform. Experiment 2 investigated the role of the corpus callosum. Split-brain rats with unilateral parietal lesions were tested on the same two tasks. Place and landmark deficits were particularly severe, but lateralization was weaker. Callosum section had its own effect, impairing the learning of both tasks. There appear to be additive effects of unilateral cortical lesions and bisection of the hemispheres. The impairment from left lesions equaled the right-lesion deficit because of the interruption of compensatory information from the intact right hemisphere and the effect of callosum section itself. PMID- 1445659 TI - Effects of prenatal exposure to cocaine on conditional discrimination learning in adult rats. AB - Adult male rats that were gestationally exposed to cocaine and control offspring were trained on an instrumental conditioning task for assessment of the acquisition and reversal of an appetitive conditional discrimination based on olfactory cues. Offspring were derived from Sprague-Dawley dams that had received subcutaneous injections of 40 mg/kg/3 cc cocaine hydrochloride (C40) daily on Gestational Days 8-20, pair-fed (PF) dams that were injected with saline, nutritional control dams (NC) that had received saline injections, and nontreated control dams (LC). There were no differences among the prenatal treatment groups in acquisition of the barpress response or response rate throughout all phases of training. All prenatal treatment groups required approximately the same number of sessions to criterion on the initial odor discrimination. In contrast, adult C40 offspring required more sessions to acquire the reversal of the conditional discrimination than did animals from the other treatment groups (PF, NC, and LC). In addition, even at criterion performance for acquisition of the reversal discrimination, C40 animals exhibited lower accuracy on the first 10 responses and made significantly more errors before the first reward. Taken together with previous results, these findings suggest that gestational exposure to cocaine results in long-lasting alterations in performance on conditioning tasks that are evident early in life and that persist into adulthood. PMID- 1445660 TI - Circadian modulation of the rat acoustic startle response. AB - The acoustic startle response (ASR) of male rats was measured during several sessions over a 24-hr period in both a light-dark cycle and a constant-dark condition. Each session consisted of 10 trials each at 80, 90, 100, 110, and 120 dB white noise. The results indicate robust daily and circadian modulation of ASR amplitude that consist of an approximately twofold nocturnal increase at eliciting-stimuli intensities above 80 dB. Similar results were observed in female rats in constant-dark conditions. To determine whether daily changes in auditory thresholds were responsible for the observed modulation, ASR reflex modification procedures were used. These procedures were designed to measure auditory thresholds at frequencies of 10 and 40 kHz at several times of day. The results suggest a lack of significant circadian differences in auditory thresholds at these frequencies. This study demonstrates a novel role of the rat circadian system in the modulation of ASR amplitude. PMID- 1445661 TI - The habenular complex mediates hormonal stimulation of maternal behavior in rats. AB - The role of the habenular complex (Hbc) in the hormonal onset and nonhormonal maintenance of maternal behavior in rats was examined. In Experiment 1, bilateral lesions were produced in the Hbc on Gestational Day (GD) 12. On GD 16, animals were hysterectomized-ovariectomized and given estradiol benzoate (EB); they were then tested for maternal behavior 48 hr later. Hbc lesions delayed the appearance of all components of maternal behavior for several days. In Experiment 2, large Hbc lesions that were produced on Postpartum Day 4 caused only 1- or 2-day deficits in maternal behavior. These data suggest that the Hbc mediates the hormonal onset of maternal behavior. During the postpartum period, however, the importance of the Hbc for maternal behavior diminishes as the hormones of pregnancy become less important. PMID- 1445663 TI - Executive summary of the AIDS Research Advisory Committee. The staff of the National Institute of Allergy and Infectious Diseases. PMID- 1445662 TI - Opioid control of the fetal stretch response: implications for the first suckling episode. AB - Upon their first experience with milk, fetal rats express a stretch response that is similar to the postnatal behavior exhibited by infant rats at the nipple. Fetuses also possess a functional opioid system that is activated by prenatal milk exposure. The opioid receptor antagonist naloxone and the specific kappa antagonist nor-binaltorphimine blocked the stretch response and prevented the increase in rearlimb activity that is typically induced by milk. The mu antagonist beta-funaltrexamine blocked the stretch while permitting the expression of rearlimb activity. The kappa agonist U50,488 promoted rearlimb activity in the absence of milk, whereas the mu agonist [D-Ala2,NMe-Phe4,Gly5-ol] enkephalin (DAMGO) exerted little influence on fetal behavior. Fetuses pretreated with U50,488 stretched to nonmilk stimuli (saline or lemon), but fetuses pretreated with DAMGO did not. Opioid activation is part of a chain of events that culminates in the fetal stretch response and may be important in promoting milk ingestion during the newborn's first suckling episode. PMID- 1445664 TI - Phase I cancer trials: limitations and implications. AB - The goal of Phase I clinical trials is to establish a maximum tolerated dose (MTD) and a tolerable dose range for future efficacy testing. Various issues include schedule of drug delivery, starting dose, number of patients to be tested, pitfalls in the selection of MTD, risk:benefit ethical issues, and the problems introduced by patient heterogeneity. Statistical evaluation of various Phase I strategies illustrate the limitations of various approaches in terms of patient expectations regarding efficacy and the scientific goals of such trials. Patients should be given the opportunity to receive the drug at more than one single dose level. PMID- 1445665 TI - A gelonin-containing immunotoxin directed against human breast carcinoma. AB - Toxins may be specifically directed to tumor cells and the toxins' potency greatly increased by covalent conjugation to monoclonal antibodies recognizing tumor-associated antigens. Antibody 15A8, an immunoglobulin G1 (IgG1) subclass anti-human breast carcinoma murine monoclonal antibody and gelonin, a plant toxin, were covalently modified with N-succimindyl 3-(2-pyridyldithio) proprionate and iminothiolane, respectively, and allowed to cross-link. 15A8 gelonin conjugates were purified from unreacted antibody and free gelonin by gel filtration and blue sepharose chromatography. Analysis by sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that the final product contained two bands corresponding to antibody:gelonin conjugates of 1:1 (predominant) and 1:2. There were no contaminating amounts of free antibody or free toxin in the preparation. The yield of the final purified 15A8-gelonin conjugate was approximately 20% based on the amount of starting antibody. The protein synthesis inhibitory activity of the immunoconjugate was assessed by in vitro rabbit reticulocyte translation assay. This functional activity was normalized to that of unmodified gelonin for use in in vitro antiproliferative assays against antigen-negative (Hs294t human melanoma) and antigen-positive (ME-180 human cervical carcinoma) cell lines. Antigen-negative Hs294t cells incubated for 72 hours with 15A8-gelonin immunotoxin showed no increased cytotoxicity compared with HS294t cells exposed to free gelonin alone. However, the immunotoxin was preferentially toxic to antigen-positive ME-180 cells; over 5 logs greater cell kill was observed after 72 hours exposure to 15A8-gelonin than after the same exposure to gelonin alone. Various lysosomotropic agents augmented 15A8-gelonin cytotoxicity; the most effective potentiating agent appeared to be monensin. In addition, the chemotherapeutic agents L-phenylalanine mustard (L-PAM), 5 fluorouracil, vincristine, and bleomycin, and the biological response modifiers interferon-alpha and tumor necrosis factor-alpha were shown to augment 15A8 gelonin cytotoxicity. Should in vivo pharmacology and therapeutic studies confirm these in vitro findings, 15A8-gelonin conjugate may be a potent agent for therapy of cancer in man. PMID- 1445666 TI - Our experience with interferon alpha: renal cell carcinoma. AB - Our 3-year clinical experience using recombinant interferon (rIFN) alpha-C in patients with metastatic renal cell carcinoma (RCC) is summarized. This type of IFN is a new subspecies of the IFN-alpha protein family. Its specific activity is 1-2 x 10(9) U/mg protein, the highest among IFN-alpha species presently available. Pharmacokinetic study indicated good bioavailability of the preparation from the intramuscular injection. A phase II study was performed to assess the response rate related to rIFN-alpha C at a low dosage. A dose of 3 x 10(6) U daily was administered, followed by 3 x 10(6) U/m2 every other day to avoid severe toxicity. Among 33 treated patients, a partial remission rate of 9.7% and stable disease rate of 25.8% were achieved. Side effects were usually mild and the treatment was well tolerated by the patients. However, mental deterioration and behavioral changes were observed in five patients with RCC treated by rIFN-alpha C and were related to neurotoxicity of IFN. The role of vinblastine in addition to IFN in the treatment of RCC was assessed in nine patients who had failed on IFN alone. No response was observed. It appeared that vinblastine had little if any effect in being added to IFN as second-line therapy. We conclude that rIFN-alpha C has moderate activity in the treatment of RCC. Familiarity with the possible toxicity of this agent will lead to more careful management of patients. PMID- 1445667 TI - Our experience with interferon alpha: metastatic malignant melanoma. AB - Interferon-alpha and dacarbazine combination is a milestone in the treatment of metastatic malignant melanoma. Objective response rate ranged from 3% to 25%. Our phase II study included 34 patients; the overall response was 29.4%. Median time of survival of the responders was significantly longer than that of the nonresponders. Nine of the 34 patients had previously progressed on interleukin-2 (IL-2) and dacarbazine treatment, or had been withdrawn because of unacceptable toxicity. Two patients (22.2%) achieved partial responses. There seemed to be no cross-resistance between the two biologic response modifiers. Successful treatment of melanoma patients by interferon resulted in complete disappearance of all extracerebral lesions, but left the brain vulnerable to involvement by metastases, and was frequently a site of relapse. Brain irradiation is suggested by several investigators to prevent cerebral involvement. Ongoing protocols are an adjuvant treatment for high-risk patients and combination of interferon-alpha, IL-2, dacarbazine and cisplatinum for metastatic melanoma after failure of interferon-dacarbazine regimen. PMID- 1445668 TI - Interferon-alpha induced autoimmune hepatitis in a patient with Philadelphia chromosome-positive chronic myeloid leukemia with cytogenetically normal T lymphocytes. AB - We report the occurrence of autoimmune hepatitis after treatment with interferon alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia. Cytogenetic and molecular genetic studies of the T lymphocytes in this patient demonstrated that the T lymphocytes were not part of the leukemic clone. The role of interferon in the production of autoimmune abnormalities is reviewed. PMID- 1445669 TI - Phytochemicals potentiate interleukin-2 generated lymphokine-activated killer cell cytotoxicity against murine renal cell carcinoma. AB - The success of adoptive immunotherapy using recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in several cancers has been hampered by severe toxicity associated with high doses of rIL-2. Methods that reduce the dosage of rIL-2 without loss of clinical efficacy are needed. In this study we determined the in vitro effect of a phytochemical immune modulator, Astragalus membranaceus (AM), and two fractions isolated by high-performance liquid chromatography on the cytotoxicity of rIL-2-generated LAK cells against a murine renal cell carcinoma. Our results indicated a 10-fold potentiation of rIL-2 generated LAK cell cytotoxicity manifested by tumor cell lysis of 88% in the group with 100 U/ml of rIL-2 plus AM versus 86% in the group with 1,000 U/ml of rIL-2 alone. Potentiation was obtained with the purified fractions as well. A significantly reduced number of LAK cells was required to achieve the tumor cytotoxicity after LAK cell generation with rIL-2 plus the phytochemicals as compared with rIL-2 alone. Our data indicate that AM is an effective immune modulator, capable of potentiating in vitro the antitumor activity of rIL-2 generated LAK cells. PMID- 1445670 TI - Application of Corynebacterium cutis lysate as an immune stimulant in cattle. AB - An ultrasonicated lysate of Corynebacterium cutis (Ultracorn, Virbac, France) was administered to 10-day-old calves, 5-month-old calves, and pregnant dams kept under Egyptian environmental conditions. Ninety-five calves and 50 dams were used in the study. All animals were treated with 2 ml/100 kg body weight of killed C cutis. Its effects on body weight gain and on calf mortality and morbidity were recorded. The results obtained showed that treated calves had greater weight gains, reduced susceptibility to common viral pathogens, and lower mortality. When given simultaneously with rinderpest vaccine, an immunopotentiating or adjuvant effect was seen. Thus, treated calves had higher neutralizing antibody titers to rinderpest as compared with untreated calves. When administered to pregnant cows in the last month of pregnancy, the offspring of these animals had higher birth weight, better weight gain, and reduced morbidity. PMID- 1445671 TI - Recombinant interleukin-2 significantly increases the survival of mice with peritonitis, but not acute Staphylococcus aureus peritoneal infection. AB - The effect of recombinant interleukin 2 (rIL-2) on survival of mice with peritonitis and acute Staphylococcus aureus strain 5/2 infection was studied. rIL 2 was ineffective in the case of acute infection when administered simultaneously with LD95 dose of bacteria. The antibiotics (gentamycin or a combination of penicillin and streptomycin) administered in the same fashion cured 100% of animals. rIL-2 proved to be a potent healing agent in the two of three models of S aureus peritonitis. In this case animals received bacteria at days 0 and 2, 4, or 6. rIL-2 was injected at day 0 (group 1), days 0 and 2 (group 2), and days 0, 2, and 4 (group 3). Treatment with rIL-2 was ineffective in group 1; however, in groups 2 and 3 rIL-2 increased the survival up to 90% (in comparison with 30% in the untreated animals of group 2 and 64% in group 3). On the contrary, administration of antibiotics instead of rIL-2 in the group 3 decreased survival to 25%. The perspectives of rIL-2 use in the treatment of bacterial peritonitis, including purous ones, and the cases complicated by immunodepression, are discussed. PMID- 1445672 TI - Structure of sp-9-hydroxy-9-pivaloylfluorene, product of base-catalyzed autoxidation of ap-9-pivaloylfluorene. AB - 1-(9-Hydroxyfluoren-9-yl)-2,2-dimethyl-1-propanone, C18H18O2, M(r) = 266.34, orthorhombic, Pbcn, a = 18.917 (10), b = 11.843 (8), c = 13.177 (7) A, V = 2952 (5) A3, Z = 8, Dx = 1.198 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 0.72 cm-1, F(000) = 1136, T = 296 K, R = 0.044 for 1042 unique observed reflections. Conversion of ap-9-pivaloylfluorene, ap-(I), into lithiated (I)-9-anion followed by the addition of MeOH, then H2O, led to unexpected hydroxylation to provide 20 40% of sp-9-hydroxy-9-pivaloyfluorene, sp-(II), and 60-80% recovery of ap-(I). The singular sp conformation of (II) in solution suggested by NMR was confirmed in the crystalline state by X-ray diffraction which showed the O(1)-C(9)-C(10) O(2) torsion angle approximately 0 degrees and the C(10) = O(2)...H(9)-O(1) non bonding distance 1.95 (4) A, suggesting strong intramolecular hydrogen bonding in this conformation. PMID- 1445673 TI - Absolute configuration of (-)-alpha-acetylmethadol hydrochloride. AB - beta-[2-(Dimethylamino)propyl]-alpha-ethyl-beta-phenylbenzeneethanol+ ++ acetate ester hydrochloride, C23H32NO2+. Cl-.H2O, M(r) = 407.9, monoclinic, P2(1), a = 15.608 (4), b = 8.637 (2), c = 17.273 (5) A, beta = 97.71 (2) degrees, V = 2307.4 (1) A3, Z = 4 (two methadol hydrochlorides and two water molecules per asymmetric unit), Dx = 1.17 Mg m-3, lambda (Cu K alpha) = 1.54184 A, mu = 1.64 mm-1, F(000) = 880, T = 295 K, final R = 0.069, wR = 0.064 for 2559 independent observed reflections. Both asymmetric C atoms in the two independent methadol molecules are 'S'. Of the two N-H moieties one acts as a hydrogen-bond donor to a Cl atom (N-H = 1.21, H...Cl = 1.85, N...Cl = 3.03 A, N-H...Cl = 162.3 degrees) and the other is a donor to a water molecule (N-H = 0.90, H...O = 2.06, N...O = 2.80 A, N H...O = 138.2 degrees). In addition, both water molecules hydrogen bond to both Cl atoms with O...Cl distances in the range 3.06-3.36 A. A comparison of torsion angles for the two independent methadol molecules indicates that there is very little stereochemical similarity between them. PMID- 1445674 TI - Structure of cis,cis-4,6-diphenyl-2-(2-propenyl)-1,3-dioxa-2-phosphorinane 2 oxide. AB - C18H19O3P, M(r) = 314.32, monoclinic, P2(1)/n, a = 5.726 (6), b = 14.234 (7), c = 20.08 (1) A, beta = 92.54 (7) degrees, V = 1635 (4) A3, Z = 4, Dx = 1.277 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 1.71 cm-1, F(000) = 664, T = 296 K, R = 0.042, 1813 unique observed reflections. The X-ray structure determination of the title compound shows that the dioxaphosphorinane ring has a chair conformation in which the phosphoryl O atom (P=O) is equatorial, which explains the absence of substantial NMR deshielding by its P=O group on H(4) and H(6), which are axial. PMID- 1445675 TI - Structure of a chiral intermediate in the synthesis of (+)-19-epiajmalicine. AB - [2S*-(2 beta,3 alpha,6 alpha,12b beta)]-Methyl 3-acetyl-1,2,3,4,6,7,12,12b octahydro-6-methoxycarbonyl-indolo+ ++[2,3-a] quinolizine-3-ethanoate, C22H26N2O5, M(r) = 398.46, orthorhombic, P2(1)2(1)2(1), a = 9.463 (2), b = 11.251 (3), c = 18.871 (6) A, V = 2009.2 (9) A3, Z = 4, Dx = 1.32 g cm-3 (178 K), lambda(Mo K alpha) = 0.7107 A, mu = 0.8762 cm-1, F(000) = 848, T = 178 K, R = 0.0536 for 1673 reflections [Fo > or = 6 sigma (Fo)]. Molecules are hydrogen bonded along the 2(1)-screw axis parallel to a. The hydrogen-bond geometric parameters for N12-H12...O19 (related by 0.5 + x, 1.5 - y, 1 - z) are N...O 2.986 (6), H...O 2.30 (5) A, N-H...O 161 (5) degrees. The C and D rings are trans fused with ring-junction torsion angles of -39.6 (5) and 63.8 (5) degrees for C12a-C12b N5-C6 and C1-C12b-N5-C4, respectively. The conformation of the C ring is half chair with N5 and C6 -0.168 (4) and 0.552 (5) A, respectively, out of the plane defined by the remaining four atoms of the ring. The D ring is in the chair conformation. PMID- 1445676 TI - (2S-[2 alpha,3 alpha,3a beta,6 beta(R*),7 alpha, 7a alpha])-6-(3-benzyloxy-2 propyl)-2-hydroxy-2,3,7-trimethylhexahydro-4H- furo [3,2-c]pyran-4-one, a rearrangement product of pyranone derivatives in the tirandamycin A series. AB - The six- and five-membered heterocyclic rings are cis-fused and adopt twist-boat and half-chair conformations, respectively. The average bond distances are: Csp3 Csp3 1.520 (6), Csp3-Csp2 1.494 (6), C-Cbenz 1.360 (10) and Csp3-O 1.425 (5) A; the C = O and Csp2-O bond lengths are 1.214 (5) and 1.324 (5) A, respectively. PMID- 1445677 TI - Structure of pentaamminechlororuthenium(III) bisulfate tetrahydrate. AB - [RuCl(NH3)5](HSO4)2.4H2O, M(r) = 487.88, triclinic, P1, a = 10.0422 (5), b = 14.1044 (7), c = 6.3273 (6) A, alpha = 100.369 (5), beta = 98.655 (6), gamma = 81.354 (4) degree, V = 864.5 (3) A3, Z = 2, Dm = 1.86 (1), D chi = 1.874 g cm-3, lambda(MO K alpha) = 0.71073 A, mu = 13.3 cm-1, F(000) = 498, T = 296 (1) K, R = 0.025 for 4622 unique reflections with I greater than 3 sigma(I). The structure contains (NH3)5RuCl2+ cations, bisulfate anions and solvate water molecules all linked by an extensive hydrogen-bonding network. Each Ru ion is coordinated in a distorted octahedral fashion by five ammonia molecules and a chloride ion. The Ru -Cl distance [2.3742 (5) A] is typical for RuIII--Cl linkages. The Ru--NH3 distances span a narrow range [2.096 (2)-2.119 (2) A] and provide no evidence for a trans effect. PMID- 1445678 TI - A chiral N-crotonyloxazolidinone Diels-Alder adduct. AB - (4S)-4-Benzyl-3-[(4S,5S)-(1-methoxy-5-methylcyclohexen-4- yl)carbonyl]-2 oxazolidinone, C19H23NO4, M(r) = 329.40, monoclinic, P2(1), a = 11.453 (3), b = 7.163 (4), c = 11.929 (2) A, beta = 111.86 (2) degree, V = 908.3 (5) A3, Z = 2, D chi = 1.20 g cm-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.79 cm-1, F(000) = 352, T = 297 K, R = 0.034 for 885 reflections with Fo2 greater than 0. The molecule is extended in the crystal; there is a small twist, -13.1 (2) degree, about the amide-like C--N bond joining the oxazolidinone ring to the carbonyl group. The configurations at the two optical centers in the cyclohexene ring confirm the anticipated stereospecificity of the Diels-Alder cycloaddition synthesis. PMID- 1445679 TI - Structure of 2,5:3,4-dianhydro-D-altritol. AB - 3,6-Dioxabicyclo[3.1.0]hexane-2,4-dimethanol, C6H10O4, M(r) = 146.1, orthorhombic, P2(1)2(1)2(1), a = 7.6209 (2), b = 9.1292 (3), c = 9.6135 (5) A, V = 668.8 (1) A3, Z = 4, Dx = 1.451 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 1.15 cm-1, F(000) = 312, T = 298 K, R = 0.029 for 1280 observations with I greater than 3 sigma(I) (of 1695 unique data). The tetrahydrofuran ring has the envelope conformation, OE, with P of 94.3 degrees and tau m = 24.0 degrees. C atoms deviate from their best plane by +/- 0.0006 (1) to 0.010 (1) A, and the O atom lies 0.331 (1) A from that plane. The epoxide O atom is syn to the tetrahydrofuran O atom. Each hydroxy group is involved in intermolecular hydrogen bonding both as donor and acceptor. The two hydrogen bonds have O...O distances of 2.743 (1) and 2.729 (1) A, and angles about H of 166.3 (12) and 172 (2) degrees, respectively. PMID- 1445681 TI - 3D structure determination from electron-microscope images: electron crystallography of staurolite. AB - Resolution of better than 2 A has been obtained in many crystals by high resolution electron microscopy. Although this resolution is sufficient to resolve interatomic spacings, structures are traditionally interpreted by comparing experimental images with contrast calculations. A drawback of this method is that images are 2D projections in which information is invariably obscured by overlap of atoms. 3D electron crystallography, developed by biophysicists to study proteins, has been used to investigate the crystal structure of staurolite. Amplitudes and phases of structure factors are obtained experimentally from high resolution images (JEOL ARM 1000 at the National Center for Electron Microscopy at LBL), taken in different directions from thin regions where dynamic scattering is minimal. From images in five orientations (containing 59 independent reflections to a resolution of 1.38 A), a 3D electron potential map is constructed which resolves clearly all cations (Al, Si, Fe, including those with partial occupancy) and all O atoms. This method has great potential in crystal structure determinations of small domains in heterogeneous crystals which are inaccessible to X-ray analysis. It is estimated that 3D structure determinations should be possible on regions only about ten unit cells wide and should resolve not only atom positions but also site occupancies. The method is also applicable to space-group determination. PMID- 1445680 TI - Structure of a tricyclic subunit of manzamine A. AB - (4a alpha,7a beta,10a beta)-2-Benzyl-1,2,3,4,4a,7,7a,8,9,10-decahydro-8,8- dimethylpyrrolo[2,3-i]isoquinolinium iodide, C20H29N2+.I-, M(r) = 424.37, monoclinic, P2(1)/n, a = 9.441 (4), b = 10.378 (4), c = 20.023 (9) A, beta = 91.56 (3) degrees, V = 1961 (1) A3, Z = 4, Dx = 1.44 g cm-3 (188 K), lambda(Mo K alpha) = 0.7107 A, mu = 16.16 cm-1, F(000) = 864, T = 188 K, R = 0.0288 for 3070 reflections [Fo greater than or equal to 4 sigma(Fo)]. The crystal structure determination was undertaken in order to establish the configuration around C10a. The rings of the isoquinoline group are trans, with the pyrrole moiety cis fused. The A ring is in the chair conformation, while the cyclohexene ring, B, is in the boat conformation owing to the cis fusion of the five-membered pyrrole ring. The pyrrole ring, C, assumes the half-chair conformation. The C-N bonds of the quaternary N atom, N8, are longer than those of the tertiary N atom, N2 [1.517 (2) for N8 and 1.463 (2) A for N2]. PMID- 1445682 TI - Polarized dispersion, glide-rule-forbidden reflections and phase determination in barium bromate monohydrate. AB - Reflections forbidden by a glide-plane rule are observed in diffraction experiments with a crystal of barium bromate monohydrate using linearly polarized synchrotron radiation with wavelength near the bromine K-absorption edge. Their intensities change with azimuth in agreement with equations derived using a tensor model of the anomalous scattering of the bromate ion and are consistent in scale with earlier measurements of that tensor in sodium bromate. The intensity of each forbidden h0l reflection gives the magnitude and phase of the bromine part of the structure factor of the allowed 2h,0,2l reflection. The x and z coordinates of the Br atom determined from such data for 11 reflections are within 0.02 A of those from two crystal structure determinations. PMID- 1445683 TI - Improving multiple isomorphous replacement phasing by heavy-atom refinement using solvent-flattened phases. AB - Solvent flattening of macromolecular MIR electron density maps is frequently used to improve the quality of the phases and the interpretability of resultant electron density maps. A new method is presented by which the heavy-atom parameters of isomorphous derivatives are refined against these same solvent flattened phases and is shown to enhance convergence of the parameters by decoupling heavy-atom-parameter adjustment from parent-phase calculation. This approach is described here in the first example of its application in the solution of the glutaminyl-tRNA synthetase-tRNA(Gln)-ATP co-crystal structure. PMID- 1445684 TI - Heavy-atom refinement against solvent-flattened phases. AB - A new algorithm for refinement of heavy-atom parameters is defined by an iterative procedure where external phases are provided by density modification. This algorithm is applied to two cases, tRNA(Asp) and the complex between tRNA(Asp) and aspartyl-tRNA synthetase. In the first case, where the structure was solved by multiple isomorphous replacement (MIR) methods, it was found that the new method gives accurate values for the native-derivative scale and four occupancy of heavy-atom sites. Position refinement was more delicate and it needed to be handled in a restricted resolution range. In the second case, where a similar method was used in the early stages of solving the phase problem, it slightly decreased the phase error. It was followed by an improvement of the density-modification masks, which led to better maps at higher resolution. PMID- 1445685 TI - A gas-chromatographic determination of the ppb levels of volatile halogenated hydrocarbons in water for injections. AB - Some volatile halogenated hydrocarbons have been found in commercial large volume parenterals (LVPs) prepared from untreated or treated (disinfected) water. To monitor the presence of volatile halogenated hydrocarbons in the source water and also in the water for injections, a low cost and sufficiently simple procedure has been developed, specifically for the following components: 1,1,1 trichloroethane, 1,1,2 trichloroethylene, 1,1,2,2 tetrachloroethylene, carbon tetrachloride, chloroform, dichlorobromomethane and dibromochloromethane. A Head space technique coupled with ECD-gaschromatography was used. The procedure is thoroughly discussed in the article, including the results of a ring test for a preliminary validation of this method. PMID- 1445686 TI - New oral system for timing-release of drugs. AB - Polymeric barriers applied by compression have already been used to control drug release rate from matrix tablets. In this paper, polymeric barrier layers, used to prepare and develop a new device able to release the drug after a programmable period of time, are described. Some matrix core formulations, containing Trapidil or Sodium Diclofenac as a model drug, were dry-coated using either a swellable or an erodible shell. This coating prevents drug release from the core until the polymeric layer is not completely eroded or swollen. The time-lag can be modified by changing the barrier formulation and/or the coating thickness. Also drug release profiles (release rate and kinetics), can be widely modified changing the barrier layer characteristics. PMID- 1445687 TI - [A new inclusion complex of silibinin and beta-cyclodextrins: in vitro dissolution kinetics and in vivo absorption in comparison with traditional formulations]. AB - The very low bioavailability of silybinin, the main constituent of silymarin, so far prevented the development of an oral pharmaceutical specialty based on this active ingredient. To overcome this difficulty, an inclusion complex between Silybinin and beta-Cyclodextrin was prepared. The new complex was compared in vitro tests (dissolution rate) and in a in vivo test (rat bile elimination) with silybinin, silymarin and one traditional formulation based on silybinin. The results show a dramatic increase in the dissolution rate of the complex (> 90% within 5 min) respect to the silybinin that confirm to be practically insoluble (< 5%). The in vivo results agree with the dissolution rates; after administration of the silybinin complex p.o., the silybinin concentration in the rat bile was near 20 times more than after administration of silybinin as is or in a traditional formulation. In the last two cases, the silybinin concentration was even 6 times less than after administration of the same amount of silymarin. These data show that the beta-CD complex solved the problem of the bioavailability of silybinin which, in the traditional formulation utilised as reference, proved to be not bioavailable. PMID- 1445688 TI - Stability of phenobarbital sodium in liquid pharmaceutical preparations. AB - Shelf-lives of liquid pharmaceutical preparations (injectable and oral solution) containing phenobarbital sodium, commercially available in Brazil, were predicted by accelerated stability test using isothermal method (at 37 degrees C, 50 degrees C and 75 degrees C). Data obtained in high temperature studies using Arrhenius relation were applied to predict shelf-lives at room temperature. The shelf-lives were calculated by linear regression analysis. UV difference spectrophotometry was used for phenobarbital determination. Thin-layer chromatography was used for separation and identification of phenylethylacethylurea, the main degradation product of phenobarbital. PMID- 1445690 TI - The microbial controls of antiseptics and disinfectants by membrane filtration: experimental evaluation of the interferences. AB - Microbiological investigations made by membrane filtration method on antiseptics and disinfectants demonstrated that the filtering membranes present very frequently a remarkable antimicrobial activity, even after washing with 300 ml of peptone water according to the guidelines of the Pharmacopoeia. The observed phenomena (appearance of inhibition zones, disappearance or decrease of the number of colonies forming units, release of antimicrobial properties to the cultural broths) can seriously diminish the validity of microbiological controls of antiseptics and disinfectants. PMID- 1445689 TI - Standardization of process parameters for salbutamol sulphate microcapsules coated with cellulose acetate phthalate and computation of in-vitro release kinetics. AB - Salbutamol sulphate, a bronchodilatatory drug for asthma, is encapsulated by Emulsion-Solvent-Evaporation technique using cellulose acetatephthalate as coating polymeric material. Different process parameters like Stirring Speed, Drug-Polymer Ratio, Solvent-Polymer Ratio, Internal Phase-External Phase Ratio, Effects of Temperature, and of Surfactants have been studied to standardise the process. At optimal condition of process parameters maximum encapsulation efficiency is obtained and microcapsules produced are free flowing and spherical. The dissolution of the microcapsules is carried out and the data obtained from in vitro dissolution profile are computed in the light of different kinetic models. Diffusion coefficient (Da) and diffusivity rate constant (KBL) are evaluated with the help of Baker-Lonsdale model. PMID- 1445691 TI - [Pharmacology of escin, a saponin from Aesculus hyppocastanum L. II. Pharmacodynamics of escin. Chapter I]. PMID- 1445692 TI - Oncogene activation in rheumatoid synovium. AB - Rheumatoid arthritis (RA) is a chronic systemic disorder that is dominated by the debilitating sequelae associated with the progressive destruction of articular joints. The molecular and cellular basis of rheumatoid joint destruction is characterized by an abnormal expression of oncogenes modulating cellular proliferation and the induction of lysosomal and metalloproteinases. Based on the observation that the synovial hyperplasia in RA is associated with the proliferation of transformed-appearing synovial lining cells and an overexpression of such oncogenes, the possibility that a hitherto unknown HTLV related retrovirus is involved in the etiopathogenesis of RA is discussed. PMID- 1445693 TI - Factors affecting quantitative assessment of Pseudomonas aeruginosa adherence to buccal epithelial cells. AB - The influence of experimental protocol on estimation of adherence of P. aeruginosa to buccal epithelial cells is highlighted. Use of membrane filtration to remove non-adherent bacteria was significantly affected by membrane pore size and rinse volume, but was not affected by inoculum size or test isolate. Even with optimum filtration conditions, over 58% of the non-adherent bacterial population were retained on the filters. Separation of non-adherent bacteria was greatly improved when density centrifugation was employed, with less than 30% of non-adherent bacteria present in the buccal epithelial suspension. Adherence values measured by a radiological and fluorometric method were significantly higher than those determined by microscopic counting. Radiological assays had the lowest variance. Gradient centrifugation was used to prepare a standard suspension of buccal epithelial cells. However, cells collected on different days showed significantly different adherence measurements. Adherence of bacteria to trypsinized buccal epithelial cells and to buccal epithelial cells from cystic fibrosis patients was similar, whereas adherence to normal buccal epithelial cells was significantly lower. PMID- 1445694 TI - Descriptive epidemiology of infections due to thermotolerant Campylobacter spp. in Norway, 1979-1988. AB - This report reviews the first ten years of Campylobacter surveillance in Norway. During 1979-1988, a total of 3,545 isolates of thermotolerant Campylobacter spp. were reported. The isolation rate increased from 1.8 per 100,000 persons per year in 1979 to 13.1 in 1988. The highest isolation rate for both sexes occurred during the first five years of life (31.0 per 100,000). A smaller second peak was detected in the age group 15-24 years (11.1 per 100,000). The male-to-female ratio was 1.52:1 for infants less than five years of age, compared with a ratio of 1.35:1 for all ages combined. Thirty-eight percent of the infections had most probably been acquired abroad. The isolation rate in urban areas (12.4 per 100,000) was over twice that observed in rural agricultural municipalities (5.5 per 100,000). However, this difference was largely due to a higher proportion of imported cases in urban areas, only small variations in isolation rate were observed when imported cases were excluded. The seasonal distribution of Campylobacter isolates showed a peak during the warm months of the year. Travel activity during summer holidays did not account for this trend, since the summer peak became even more pronounced when imported cases were excluded. A north-south gradient in the seasonality was observed; when domestic cases were considered, the summer peak became more accentuated with increasing latitude reaching a maximum in subarctic areas. This might be explained by corresponding variations in occurrence of campylobacters in surface water sources. PMID- 1445695 TI - Capsular polysaccharide is linked to the outer surface of type 6A pneumococcal cell walls. AB - The in situ attachment of capsular polysaccharide of type 6A pneumococci was examined by immunoelectron microscopy using anti-type 6A monoclonal antibody. The result discloses an asymmetrical cross-section of pneumococcal cell walls because capsular polysaccharides are located on the outer surface of the walls only, in contrast to the cell wall polysaccharide, which has been shown to be located on both surfaces. PMID- 1445696 TI - Serum levels of fetal antigen 2 in hyperthyroidism and primary hyperparathyroidism. AB - Serum concentration of fetal antigen 2 (FA2) in patients with hyperthyroidism (n = 18) (median: 12.9 mAU/l; range: 3.2-22.4 mAU/l) was significantly (p < 0.002) higher than in age- and sex-matched healthy controls (median: 4.1 mAU FA2/l; range: 2.4-10.0 mAU FA2/l). Serum FA2 was positively correlated with thyroxine (T4) (Rs = 0.51; p < 0.05), triiodothyronine (T3) (Rs = 0.64; p < 0.01), bone-Gla protein (BGP) (Rs = 0.70; p < 0.01), total alkaline phosphatase (total-AP) (Rs = 0.62; p < 0.01), bone isoenzyme alkaline phosphatase (bone-AP) (Rs = 0.63; p < 0.01), N-terminal procollagen type III (PIIINP) (Rs = 0.65; p < 0.01) and urine OH-proline (OHP) (Rs = 0.79; p < 0.01). In patients with hyperparathyroidism the pretreatment levels of FA2 (n = 8) (median: 17.6 mAU/l; range: 5.2-35.0 mAU/l) were significantly (p < 0.001) higher than those of age- and sex-matched controls (median: 3.7 mAU FA2/l; range: 3.4-9.0 mAU/l). The pretreatment level of FA2 was positively correlated with the parathyroid hormone (PTH) (Rs = 0.80; p < 0.05). Following surgical treatment the serum concentrations of FA2, PTH, and BGP decreased compared to pretreatment levels and the fall in these three parameters revealed parallelism. These data indicate that serum FA2 can be used as a marker in the evaluation of metabolic bone diseases. PMID- 1445697 TI - Haemagglutination patterns of Helicobacter pylori. Frequency of sialic acid specific and non-sialic acid-specific haemagglutinins. AB - Thirty-two Helicobacter pylori strains were screened for haemagglutination (HA) activity with erythrocytes of 11 different animal species. Twenty-three strains (72%) that agglutinated human erythrocytes exhibited a broad-spectrum HA profile. Human, guinea pig and bovine erythrocytes high in sialoglycoconjugates were strongly agglutinated by most strains. Except for two, seven strains (22%) that did not agglutinate human erythrocytes exhibited a narrow-spectrum HA profile, commonly not inhibitable by sialoglycoconjugates or N-acetylneuraminlactose (NANLac). Strains were classified into three major HA classes. HA of 10 strains (31%) in class I was inhibited by different combinations of NANLac, orosomucoid or fetuin, but not by asialofetuin, suggesting the presence of sialic acid specific HAs probably recognizing NeuAc alpha-(2-3)- Gal isomer. Twelve strains (38%) in class II exhibited a different receptor specificity binding to different combinations of NANLac, orosomucoid and fetuin, as well as asialofetuin. No inhibition was observed with 10 strains (31%) in class III; thus, this receptor seems different from both the other classes. Of 21 strains (66%) in classes I and II, HA of 11 strains (34%) was inhibited with NANLac, 14 strains (44%) with orosomucoid and 15 strains (47%) with fetuin. The great heterogeneity observed in HA patterns indicates that the HAs of different strains may recognize a heterogeneous class of sialoglycoconjugates on the erythrocyte membrane. PMID- 1445698 TI - Ultrastructural morphometric analysis of human blood platelets exposed to minimal handling procedures. AB - A detailed morphometric study of normal human blood platelets is described. The purpose has been to evaluate the morphological characteristics of platelets exposed to minimal handling procedures in order to obtain an optimal basis for the appraisal of platelets in disease. Blood from 10 healthy volunteers was collected directly into buffered glutaraldehyde and processed for electron microscopy. This platelet fixation procedure resulted in excellent preservation of resting platelet ultrastructure with one exception: the dense bodies. Compared to platelets fixed following washing procedures, our directly fixed platelets comprised fewer pseudopods and contained more glycogen. An unexpected feature of the open canalicular system was the apparent release of blisters interpreted as microvesicles. Employing a computerized image analyzer, 300 of the platelets were examined morphologically. The morphometric data thus obtained were analyzed statistically, resulting in a set of standard values for morphological characteristics of human platelets which we have found useful in subsequent evaluations of platelet morphology in disease. Significant inter-individual variance was, however, detected in two instances, in the section area of the alpha granules, as well as the area fraction of platelet sections occupied by channels of the open canalicular system (OCS). This should be taken into consideration when appraising platelet ultrastructure in health and disease. PMID- 1445699 TI - Tumours in Iceland. 16. Malignant tumours of the stomach. Histological classification and description of epidemiological changes in a high-risk population during 30 years. AB - Iceland is one of the high-risk countries for stomach cancer. During the period 1955-84 the incidence declined from 76 to 28 per 10(5) p.a. for males and from 30 to 12 for females. Tissue material from the primary site in 978 males and 448 females was available for histological typing. By the WHO classification tubular carcinoma was most frequent in both sexes, 66% in males and 63% in females, and signet-ring carcinoma second, 13% in males and 16% in females. By the Lauren classification in males 78.1% were intestinal and 16.5% diffuse carcinomas, and in females 73.1% were intestinal and 20.7% diffuse carcinomas. The decline in stomach cancer in Icelanders has mostly affected the intestinal type of tumour (Lauren) and the tubular type of tumour (WHO). Diffuse type tumours (Lauren) have declined slightly. This supports the theory that intestinal carcinomas are more influenced by environmental and especially dietary factors, and that diffuse carcinomas are more influenced by other as yet unknown factors. For epidemiological studies both histological classifications have their value, the WHO especially in that it is based on standard histopathological criteria and the Lauren especially in that it only includes two tumour types. The WHO classification can roughly be transcribed to the Lauren classification as tubular, mucinous and papillary carcinomas fall into the group of intestinal tumours, and signet-ring and more than half of undifferentiated carcinomas into the group of diffuse tumours. PMID- 1445700 TI - Tumours in Iceland. 17. Malignant tumours of the oesophagus. Histological classification and epidemiological considerations. AB - We studied all primary malignancies of the oesophagus diagnosed in Iceland between 1955 and 1984 and reclassified tumours where histological material was available using the WHO classification system. Of a total of 329 tumours diagnosed in the time period, seven were excluded for various reasons. Of the remaining 322 tumours, 178 were in males and 144 in females. The age standardized incidence was 5.3/10(5) for males and 3.1/10(5) for females. The incidence of oesophageal tumours decreased for both sexes during the time period under investigation. Of 250 reclassified tumours (142 in males and 108 in females), squamous cell carcinomas comprised 81.6%. If the undifferentiated tumours are excluded, the squamous group accounted for 89.1% of the remaining tumours. Small cell carcinomas comprised 3.2% of all cases, which was higher than expected. Most of the tumours appear to be located in the middle part of the oesophagus. The vast majority of resected tumours extended through the wall of the oesophagus. A relatively higher proportion of tumours was confined to the submucosal or muscular layers in the latter half of the period. In conclusion, the epidemiological data in our study appear to resemble what is observed in the other Nordic countries for oesophageal tumours, except for slightly higher overall incidence in Iceland, especially for women. PMID- 1445701 TI - Detection of gastrin mRNA by in situ hybridization using radioactive- and digoxigenin-labelled probes: a comparative study. AB - The hormone gastrin is mainly produced by the G cells of the antral mucosa and plays a major role in the regulation of digestive mucosal growth. Since it permits identification of cell types containing mRNA, in situ hybridization (ISH) appears to be an interesting method for studying gastrin-producing tissues. In this study, in situ detection of gastrin mRNA has been carried out on frozen sections of four human normal antral mucosa samples and of six colonic carcinomas removed from patients with high levels of plasma gastrin, using a gastrin oligonucleotidic DNA probe. We have compared the results provided respectively by the [35s] labelling and the digoxigenin labelling of the synthetic probe. Positive cells were found in each normal sample analysed with radioactive- as well as digoxigenin-labelled antisense probes. The total number of cells expressing gastrin mRNA appeared slightly higher with the [35s]-labelled probe, while the digoxigenin-labelled probe gave a better definition of positive signals. In contrast, neither radioactive nor cold probes gave positive signals in the six colonic carcinoma samples, although gastrin expression had been demonstrated in these tumours using a reverse transcriptase-PCR method. These results show that, although ISH does not seem sensitive enough to allow the detection of very low levels of gastrin expression, it would appear to be a reliable method for visualizing gastrin mRNA in human antral mucosa. PMID- 1445702 TI - beta-lactamases in Shigella. AB - The occurrence of resistance and production of beta-lactamases was investigated in 60 Shigella strains. Ampicillin resistance was found in 28 (47%) of the isolates, the resistance being more frequent in Sh. flexneri than in Sh. sonnei. All strains were susceptible to cefotaxime, mecillinam, and ciprofloxacin. The beta-lactamases produced by Shigella were similar to TEM-1, OXA-1, or the low level chromosomally mediated cephalosporinase produced by Escherichia coli. The beta-lactamases produced by Sh. flexneri were most often the OXA-1-like enzymes. PMID- 1445703 TI - Factors to be considered in the evaluation of bioavailability and bioequivalence of topical formulations. AB - In this paper, an attempt is made to find functional definitions of bioavailability and bioequivalence for topical products and to examine critical factors that influence topical bioavailability and bioequivalence. A physical model approach for quantifying the problem and increasing our understanding is presented here. The key assumptions are (1) that the target site is in the lower epidermis (basal layer) or in the dermis, and (2) that it is the thermodynamic activity (i.e., the free drug concentration, C*, of the active drug species) at the target site that is the true correlate of drug effectiveness. Studies initiated to implement the physical model approach involved first validating a 'three-tiered' model for finite dose drug uptake/transport in skin with experimentally determined input parameters (partition coefficient, K, and steady state permeability coefficients, P, for the stratum corneum, viable epidermis, and dermis). Hydrocortisone was used as the model drug with hairless guinea pig skin as the model membrane. The physical model is used to show, via the C* concept, how formulation factors may influence bioavailability and bioequivalence. Finally, a method is presented for predicting the efficacy of topical formulations employing appropriate in vitro data and physical model calculations. PMID- 1445705 TI - Topical and systemic absorption of sodium pyrithione following topical application to the nails of the rhesus monkey. AB - A study was performed to investigate the local penetration into the nail, the systemic absorption into the rest of the body, and the routes of excretion of sodium pyrithione following topical application to the nail. Approximately 20 microliters of a film-forming 3% sodium 14C-pyrithione solution was applied once daily to 5 fingernails and 5 toenails of 4 rhesus monkeys for 6 or 7 days. Following dose removal on study day 7, 2 animals were sacrificed, and the treated nails were analyzed for radioactivity. The other 2 monkeys received the topical dose for 1 more day and were monitored during the postdosing period. Sodium 14C pyrithione was absorbed slowly into and across the nail following topical application, with the nails serving as reservoirs for the drug. Further evidence of the slow movement of sodium pyrithione across the nail was provided by peak plasma 14C equivalents obtained on day 9, 1 day after the last dose had been removed from the nails. Only slight drug concentrations were measurable in plasma, with no radioactivity observed beyond day 12. The urinary excretion data exhibited a delay in peak urinary excretion (days 8 and 9), and an elimination half-life of 2 days, so that approximately 90% of the absorbed drug was eliminated within 1 week following treatment. Including a minor excretion pathway through the feces, total excretion as a percent of dosage was 8.5%, indicating that less than 10% of the applied topical dose of sodium pyrithione was absorbed systemically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445704 TI - Absorption and metabolism of topically applied testosterone in an organotypic skin culture. AB - The Living Skin Equivalent (LSE) is an organotypic coculture of human dermal fibroblasts in a collagen-containing matrix and a stratified epidermis composed of human epidermal keratinocytes. In order to establish the feasibility of using this in vitro system as a model for cutaneous biotransformation, the metabolic fate of topically applied testosterone (T) was monitored in the LSE. After a 24 hour exposure period (37 degrees C) to radiolabelled T, LSE extracts analyzed by high-performance thin-layer chromatography showed that approximately 50% of the applied T had been metabolized. Identified metabolites included bands which comigrated with polar metabolites and products of T 5 alpha-reductase. The general distribution of the observed metabolites was similar to that obtained using biopsied human skin. The rates of T penetration (32 degrees C) through the LSE were monitored after application of T in two vehicles (water and petrolatum) and yielded permeability constants (Kps) of 29 and 1.6 x 10(-3) cm/h, respectively. These Kp values were 4- to 6-fold higher than those reported for human abdominal skin, and reflect the vehicle-related shift in penetration seen in human skin. The Kp values for two additional steroids, estradiol and hydrocortisone, and for T were also determined at 22 degrees C and compared to published Kp values. These Kp values in the LSE were, respectively, 63-, 187- and 35-fold higher than those reported for human skin. The data suggest that compared to human skin the LSE has only a partial barrier function to the passage of test chemicals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445706 TI - The possibility of lidocaine ion pair absorption through excised hairless mouse skin. AB - The purpose of the present research was to test the ion pair absorption hypothesis with respect to the topical route of drug delivery. The experiment consisted of preparing various lidocaine-n-alkanoate ion pairs, then characterizing them by proton magnetic resonance spectroscopy, elemental analysis and conductivity. Percutaneous absorption studies through excised hairless mouse skin were carried out using ethanolic solution of radiolabeled 14C-lidocaine octanoate, 14C-lidocaine-decanoate and 14C-lidocaine-dodecanoate. Studies were conducted under steady-state conditions using Bronaugh's flow-through apparatus and normal saline as the receptor fluid. Ethanolic solution of a lidocaine base served as a control. The apparent differences in flux between lidocaine and the various ion pairs were statistically significant (p less than 0.05). The differences among the fluxes of the various ion pairs were not statistically significant (p greater than 0.05), nor were the differences in lag times (p greater than 0.05). The difference between the flux values of lidocaine-1-14C dodecanoate and 14C-lidocaine-dodecanoate infers that lidocaine-dodecanoate did not cross the excised, full-thickness, hairless mouse skin as an intact 1:1 ion pair. The formation of weakly associated ion pairs was suggested by the apparent low-association constants (Ka = 15-17 liters/mol) obtained at 25 degrees C in methanol by conductometric analysis. PMID- 1445707 TI - In vivo microdialysis estimation of histamine in human skin. AB - Microdialysis, a new bioanalytical sampling technique, enables the measurement of substances in the extracellular space. This study investigates the use of the technique in the in vivo measurement of histamine levels in human skin. Microdialysis probes are equipped at the tip with a semipermeable polycarbonate membrane which permits the passive diffusion of substances. 16 probes were inserted, via a guide, into the skin of the ventral forearm of 8 patients or volunteers. The probe was perfused at a flow of 5 microliters/min, with samples being collected at intervals of 10 min and analysed by RIA technique. The mean histamine level in the first 10-min sample following probe insertion was 39.4 nM. The mean histamine value fell with successive 10-min samples (8.8, 4.6, 2.3 nM). An equilibration period of 40 min following probe insertion is suggested for histamine studies, where provocation of the skin is to be performed. Microdialysis appears to be a promising new tool for quantitative and chronological studies of cutaneous inflammatory mediators. PMID- 1445708 TI - Repeated application of dinitrochlorobenzene to the ears of sensitized guinea pigs: a preliminary characterization of a potential new animal model for contact eczema in humans. AB - We have evaluated a subchronic model of contact hypersensitivity in the guinea pig to mimic human chronic/recurrent eczema. Repeated challenges of the ears of previously sensitized guinea pigs with 0.1% dinitrochlorobenzene (once a week for 4 weeks) induced a typical oedema response, which increased during the first 48 h after each challenge. Crusts were detectable (48 h after challenge) and histological observations (72 h after challenge) revealed hyperplasia, papillomatosis, hyperkeratosis and some mononuclear cell infiltrates in the dermis. In agreement with clinical observations in humans, topical treatment of challenged animals with corticosteroid (1% hydrocortisone) reduced the oedema, hyperplasia, papillomatosis, and leucocyte infiltrates, while application of 5% bufexamac (a non-steroidal drug) was associated with a slight enhancement of the inflammatory response. Thus, this model presents clinical and histological similarities with human eczema. Its pharmacological relevance is also suggested, although further investigations are required to better define its selectivity. PMID- 1445709 TI - [Carpal tunnel syndrome: clinical , electromyographic and therapeutic aspects]. PMID- 1445710 TI - [The results of drug holiday in Parkinson's disease]. AB - The transitory suppression of L-dopa in patients with advanced Parkinson's disease improves motor response upon reintroduction of the drug although this improvement is not constant. The degree and duration of clinical improvement obtained following L-dopa drug holiday were studied and the factors which may intervene in the result of 32 patients with Parkinson's disease were analyzed. Improvement was found in 100% (24.9 +/- 6.7%) with significant differences being observed in the degree of disability (p < 0.05) and the final decrease of the doses of L-dopa (p < 0.05). Improvement was maintained during 10.3 +/- 7.9 weeks. Linear regression studies did not show any relation between the length of the drug holiday, longer than 4 days, and the degree and maintenance of improvement or final decrease of the doses of L-dopa. The authors consider this procedure useful in patients with important fluctuations in treatment response or with important refractory side effects to other measures. PMID- 1445711 TI - [Carotid surgery in Spain. Analysis of 2 national inquiries]. PMID- 1445712 TI - [Treatment with ubiquinone in Kearns-Sayre syndrome. Improvement in ocular motility and visual evoked potentials]. AB - In 1985 Ogasahara observed that treatment with ubiquinone produced improvement in the cardiac conduction and the metabolism of the lactic and pyruvic acids in the Kearns-Sayre syndrome. The results of the administration of 150 mg/day of ubiquinone for 3 years in a patient diagnosed with the Kearns-Sayre syndrome is described. The patient improved notably in strength, ocular movement, visual evoked potentials and in the metabolism of lactic and pyruvic acids. Other beneficial effects reported in the literature have been improvement of ataxia and the somato-sensitive evoked potentials. No side effects have been described. PMID- 1445713 TI - [Rhombencephalitis caused by Listeria monocytogenes]. AB - The observation of an abscess in the brain stem and cerebellum due to Listeria monocytogenes is presented. The patient was a 55 year old diabetic, alcoholic, gastrectomized male in whom a febrile and meningeal syndrome developed. Three days later he had a progressive unilateral dysfunction of the cranial nerves. The cerebrospinal fluid showed pleocytosis of the polymorphonuclear cells, an increase in proteins and low glucose in relation with the glycemia. No parenchymatous lesion was observed upon emergency computerized tomography. Magnetic resonance imaging showed a hyper-signal lesion in the brain stem and cerebellum with a contrast enhancement in ring. Following antibiotic treatment the clinical evolution of the patient was favorable with slight focal sequelae persistent at discharge. A review of the epidemiology, clinical manifestations and treatment of this infection is carried out. PMID- 1445714 TI - [Binswanger disease and antiphospholipid antibodies]. PMID- 1445715 TI - [Primary cerebral T-cell lymphoma in a previously healthy patient]. PMID- 1445716 TI - [Cryptococcal meningitis in an immunocompetent patient: efficacy of fluconazole]. PMID- 1445717 TI - [Painful ophthalmoplegia associated with infectious mononucleosis]. PMID- 1445718 TI - [Agenesia of the corpus callosum associated with cerebellar vascular malformation]. PMID- 1445719 TI - [Sneddon's syndrome and antiphospholipid antibodies]. PMID- 1445720 TI - [Neurophysiologic evaluation in patients with Behcet's disease]. PMID- 1445721 TI - Amino acid substitution of proteins coded for in mitochondrial DNA during mammalian evolution. AB - Three Markov models (Dayhoff, Proportional and Poisson models; Hasegawa et al., 1992a) for amino acid substitution during evolution were used for maximum likelihood analyses of proteins coded for in mitochondrial DNA in estimating a phylogenetic tree among human, bovine and murids (mouse and rat) with chicken as an outgroup. It turned out that Dayhoff model is the most appropriate model among the alternatives in approximating the amino acid substitutions of proteins coded for in mitochondrial DNA. In spite of the presence of the complete sequence data of mitochondrial genomes, we could not resolve the trichotomy among human, bovine and murids, probably because the time length separating two branching events among these three lines was short and because chicken is too distant from mammals to be used as an outgroup. It was suggested that the average substitution rate of amino acids coded for in mitochondrial DNA is lower along the bovine line than those along the human or murid lines. Advantages of amino acid sequence analysis over nucleotide sequence analysis in phylogenetic study were discussed. PMID- 1445722 TI - Compensatory changes in silver-stainability of nucleolar organizer regions in mice. AB - Silver-stainability of nucleolar organizer regions (NORs) that contain genes for ribosomal RNA (rDNA) was investigated using two mouse strains, BALB/cCrSlc and MOA, and their hybrid progeny. The patterns of segregation of the rDNA clusters were analyzed in terms of chromosomal C-banding and by use of a polymorphic probe for the variable region in backcrossed N2 and N3 individuals. The results indicate that the intensity of Ag-NOR staining is stably inherited in most of the rDNA clusters, irrespective of different genetic backgrounds. In some clusters, such as those on chromosome 12 of BALB/cCrSlc, a modulation of the intensity is observed. This modulation seems to be due to compensatory activation via a change in the number of actively transcribed genes. The change from silver-negative to silver-positive staining of the NOR of chromosome 12 of BALB/cCrSlc was correlated with demethylation of the genes. PMID- 1445723 TI - Cytological mapping of Om mutants of Drosophila ananassae. AB - Semidominant, optic morphology (Om) mutants in Drosophila ananassae have been genetically mapped to at least 25 loci throughout the genome (Hinton, 1984; 1988). Among them, four X-linked Om mutants were proved to be associated with the insertion of a transposable element, tom (Shrimpton et al., 1986; Tanda et al., 1988). In the present study, cytological mapping of autosomal Om mutants was carried out by in situ hybridization to polytene chromosomes using a cloned tom element as a probe. The cytological site for each autosomal Om mutant has been determined to a single band of the salivary gland chromosomes. PMID- 1445724 TI - Radiation from Chernobyl and risk of childhood leukaemia. PMID- 1445725 TI - Trends in mortality from malignant cutaneous melanoma in The Netherlands, 1950 1988. AB - This paper presents an analysis of trends in mortality from malignant melanoma of the skin in The Netherlands, 1950-1988. Statistical analyses show that time period effects are needed to describe the mortality trends in The Netherlands. Because this contrasts with reports from other countries, in which the trends were ascribed to a cohort effect only, log-linear models including the three factors age, time period and birth cohort, were fitted to the data. To be able to separate time period effects from birth cohort effects we assumed a mathematical function for the mortality rates in relation to age. The results obtained in this way indicate that time period effects increased up to 1970. An increase of birth cohort effects is seen for cohorts born between 1900 and 1955. For cohorts born after 1955 the mortality from melanoma seems to decrease. The most plausible explanation for the time period effect probably is improvement in death certification. PMID- 1445726 TI - Diet and colorectal cancer: results of two case-control studies in Russia. AB - Two case-control studies of diet and colorectal cancer were conducted in Moscow and Khabarovsk. The Moscow study comprised 100 cases of colorectal cancer and 100 neighbourhood controls. The Khabarovsk study consisted of 117 cases of colorectal cancer and 117 population controls. A history of the usual dietary intake one year prior to interview was taken using a food frequency questionnaire. Effects were adjusted in analysis for energy intake and education. Significantly reduced risks were observed with high intakes of cellulose (P = 0.001), beta-carotene (P = 0.002), vitamin C (P = 0.007), polyunsaturated fatty acids (PUFA) (P = 0.004), cholesterol (P = 0.04), and with a high ratio of PUFA to saturated fatty acids (SFA) (P = 0.002). Significant increases in risk were observed in association with high ratios of intakes of protein to cellulose (P = 0.002) and of fat to cellulose (P = 0.008). High intake of total fat was associated with non significant decrease in the risk (P = 0.12), while high intake of SFA resulted in statistically non-significant increase in risk (P = 0.40). Significant reductions in risk were associated with high frequencies of consumption of vegetables (P = 0.001) and fruit (P = 0.009). There were results suggestive of a decreased risk with a high frequency of milk consumption (P = 0.06) and an increased risk in association with a ratio of meat to vegetable frequencies (P = 0.09). After adjustment among factors effecting risk of colorectal cancer statistically significant increase in the risk was seen only for protein/cellulose ratio and significant protective effect for PUFA/SFA ratio, beta-carotene and vegetable consumption. PMID- 1445727 TI - Metabolic response of AH13r rat tumours to cyclophosphamide as monitored by pO2 and pH semi-microelectrodes. AB - The composition of the microenvironment has an important influence on the cellular response to cytotoxic agents. Using pH and pO2 semi-microelectrodes, we have monitored metabolic changes in AH13r rat tumours as a function of time after subcurative chemotherapy. Prior to therapy, tumours contained large areas considered hypoxic (mean pO2 approximately 4 mmHg) and are characterised by a marked accumulation of acidic metabolites (mean pH 6.65). Administration of cyclophosphamide (40 mg/kg body weight) resulted in tumour regression to 15% of pretreatment volumes and a growth delay of 12 days. Concomitant with volume reduction, tumours became reoxygenated (mean pO2 approximately 7 mmHg), with maximum values being reached within 2-4 days, paralleled by a shift of pH to more alkaline values (0.17 U on average). These changes coincided with the development of subtotal necrosis. During early tumour regrowth, the pH and pO2 histograms returned to control values. These data corroborate and extend the results of previous studies in which noninvasive techniques had been applied for the monitoring of treatment-induced metabolic changes in malignant tumours in vivo. In addition, these results support the notion that the effectiveness of anticancer therapy might be improved by selecting and scheduling therapeutic agents in consideration of physiological changes caused by preceding courses of treatment. PMID- 1445728 TI - Survival trends for neuroblastoma patients in Finland: negative reflections on screening. AB - Based on 257 neuroblastoma patients in the age group 0-14 years and reported to the Finnish Cancer Registry, the 5-year cumulative survival rates have improved from 15% in the 1950s to 57% in 1980-1986. The potential benefit of screening for neuroblastoma was assessed on the basis of these nationwide survival trends. It is likely that any decrease in the overall neuroblastoma mortality due to screening would be small, because the survival rates of the Finnish neuroblastoma patients are already, even without screening, similar to those in Japan, which has a nationwide public health policy to screen for neuroblastoma. PMID- 1445729 TI - Effect of dequalinium on K1735-M2 melanoma cell growth, directional migration and invasion in vitro. AB - Cationic lipophilic compounds have an antiproliferative effect on certain tumour systems in vitro and in vivo. We have investigated whether the cationic lipophilic compound dequalinium affects not only proliferation but also motility and invasion of the highly metastatic and highly invasive melanoma cell line K1735-M2. Proliferation was assessed in monolayer cultures and in multicellular spheroids, motility was estimated in the assay of directional migration, and invasiveness was tested through confrontation cultures of tumour multicellular spheroids with embryonic chick heart tissue evaluated by computerized image analysis. 2 mumol/l dequalinium impaired melanoma cell proliferation, reduced directional migration and significantly blocked invasion in vitro. On the ultrastructural level, dequalinium caused obvious changes in mitochondria of both melanoma and embryonic chick heart cells. The mechanisms of the antiproliferative, antimigrating and antiinvasive effects remain to be determined. Inhibition of protein kinase C, calmodulin antagonism, DNA intercalation and/or direct effects on mitochondrial functions may be considered. PMID- 1445730 TI - Long-term stability of 5-fluorouracil and folinic acid admixtures. AB - 5-Fluorouracil (5-FU) and d,1-folinic acid (FA) are used in association to treat a wide variety of malignancies. The stability and the compatibility of 5-FU and FA in combination in intravenous admixtures were studied under various storage conditions and with drug concentrations matching their clinical use (0.9% sodium chloride, 5% dextrose, protected from light or not). 5-FU and FA concentrations (mg/ml) were 6.5 or 50 and 4.0 or 30.8, respectively. Successive aliquots of the drugs mixtures were withdrawn during 60 h from 500 ml glass bottles and 500 ml polyvinyl chloride (PVC) bags (at room temperature) and during 120 h from cassettes (at 32 degrees C). Drug concentrations were measured by high performance liquid chromatography. For all conditions tested, the changes in 5-FU and FA relative to the initial concentrations remained within the assay reproducibility (10%). In complement, infrared Fourier transformation spectrophotometry has not shown a significant fixation of FA or 5-FU on the PVC bags, in all tested conditions. Under the conditions examined above 5-FU and FA can be mixed in the same container for their use in cancer chemotherapy. This can have practical consequences by simplifying the widely used treatment protocols associating 5-FU and FA. PMID- 1445731 TI - Serum osteocalcin in the management of myeloma. AB - We have measured serum osteocalcin, a vitamin K-dependent glycoprotein synthesised by osteoblasts in 62 patients, 49 with myeloma, 26 at presentation and 23 previously treated, 7 with Waldenstrom's macroglobulinaemia (WM), and 6 with monoclonal gammopathy of uncertain significance (MGUS). Osteocalcin levels were normal in WM and MGUS. High values were found in 5/26 (19%) patients with myeloma at presentation. There was no relationship between serum osteocalcin and stage of disease. Osteocalcin was normal in all patients in plateau phase, falling to low levels in relapsed patients who failed to respond to further treatment. Serum osteocalcin may be a useful indicator of bone metabolism in myeloma. PMID- 1445732 TI - Phase II study of fotemustine in advanced soft tissue sarcomas. A trial of the EORTC Soft Tissue and Bone Sarcoma Group. PMID- 1445733 TI - CA 15.3 determination in patients with breast cancer: clinical utility for the detection of distant metastases. AB - In 81 healthy women, 26 pregnant women, 25 patients with fibrocystic disease and 144 breast cancer patients, the overall diagnostic sensitivity and specificity of the CA 15.3 test was 27 and 97%, respectively. The positive and negative predictive values were 93 and 43%. In 150 node-negative patients taking part in a chemoprevention trial CA 15.3 was assayed at baseline and every 4 months for a median follow-up of 24 months (range 4-48). In these patients, 5 had local recurrences, 1 had a regional recurrence, 9 had distant metastases and 3 developed cancer in the contralateral breast. Among the patients with recurrences, those with distant metastases showed the highest ratio of CA 15.3 increase (8/9); in local and regional recurrences, this ratio was lower (2/6). The patients with contralateral breast cancer had no significant increase in CA 15.3. Patients in whom metastases were detected showed an increase in CA 15.3 4 48 months before clinical or instrumental detection of the metastases. PMID- 1445734 TI - Diethylstilboestrol: II, pharmacology, toxicology and carcinogenicity in experimental animals. AB - Diethylstilboestrol (DES) exerts several toxic effects in experimental animals, by mechanisms which are still unclear. The genotoxicity of the drug has been attributed to a quinone metabolite and is mainly clastogenic, including sister chromatid exchange, unscheduled DNA synthesis, chromosomal aberrations, disruption of mitotic spindle and aneuploidy. There is evidence that genotoxic effects may occur also transplacentally. Intrauterine and early postnatal exposure to DES can cause a variety of dysplasias. In the offspring of female mice exposed to DES during pregnancy, histological changes are observed in the vaginal and cervical epithelium, the endometrium, the ovary, the testis and the epididymis. Prenatal exposure of rats to DES led to decreased litter size and to urethrovaginal cloaca, penile and testicular hypoplasia, and cryptorchidism. Vaginal ridging, vaginal adenosis, testicular hypoplasia and cryptorchidism have been observed in rhesus monkeys following prenatal exposure. There is sufficient evidence that diethylstilboestrol is carcinogenic in experimental animals, after either prenatal or postnatal exposure. Mice show a similar type of carcinogenicity to that observed in humans, target organs being vagina, cervix, uterus, ovary, mammary gland and testis. In rats, prenatal exposure to DES produces mostly mammary and pituitary tumours, but also some tumours of the vagina. Hamsters develop tumours of vagina, cervix, endometrium, epididymis, testis, liver and kidney. DES induces ovarian papillary carcinomas in dogs, and malignant uterine mesotheliomas in squirrel monkeys. Some experimental evidence points to the possibility of a transgenerational carcinogenic effect, since prenatal treatment of mice with DES is followed by an increased incidence of uterine and ovarian carcinomas in the second-generation descendants. Experimental results could have been used to predict the adverse effects of DES observed in humans in the early 1970s: DES had been reported to be carcinogenic in mice in the 1930s, while experiments in the 1960s had provided evidence that exposure during pregnancy could result in an increased cancer risk in the progeny. PMID- 1445735 TI - Long term effects of tamoxifen. Biological effects of Tamoxifen Working Party. AB - A total of 153 breast cancer patients who participated in two trials of adjuvant tamoxifen and who had not recurred were recruited into a study of the long term effects of tamoxifen. There were 60 controls (no tamoxifen), 73 ex-users (mostly for 2 years) and 20 current users (median treatment duration 72 months) and the median follow-up time was 7 years. A wide ranging study of lipids, hormones, bone density and haemostasis was undertaken. When compared with controls, current users had lower cholesterol levels (especially low density cholesterol), and increased triglyceride levels. Thyroid hormones were higher and sex hormone binding globulin was almost doubled. Bone density was non-significantly higher, clotting times were slightly shorter and fibrinogen and antithrombin III levels were reduced. However few of these changes persisted in ex-users, suggesting that most of the biological effects of treatment are reversible on cessation of treatment. This is reassuring for potentially negative side-effects, but also indicates that potentially positive 'side-effects' such as cholesterol lowering only occur while on active treatment. PMID- 1445736 TI - Role of mitochondria in carcinogenesis. PMID- 1445738 TI - Left handedness and breast cancer. PMID- 1445737 TI - Left handedness and breast cancer risk. PMID- 1445739 TI - Cell kinetics in management of ovarian cancer. PMID- 1445740 TI - Chemotherapy induced amenorrhoea in a randomised trial of adjuvant chemotherapy duration in breast cancer. AB - We have previously reported the results of a clinical trial in patients with stage II breast cancer which compared a 12 week chemohormonal regimen with a 36 week chemotherapy regimen. Both pre and post menopausal women were entered. The 12 week regimen was inferior both in terms of disease-free survival and overall survival. The effect of chemotherapy on menstrual function was prospectively documented in 95 of 114 premenopausal women at 3 of the 4 participating centres. 67 of the 95 women (70.5%) developed permanent amenorrhoea. There was a statistically significant difference in the rate of induced amenorrhea between the 12 week and the 36 week groups; 23/42 vs. 44/53, respectively (P = 0.003). Recurrence and mortality rates were lower in the patients who became amenorrheic; 38% vs. 57% (P = 0.03) and 18% vs. 32% (P = 0.17), respectively. Similar trends were observed within treatment groups. The effect of induced amenorrhoea on outcome was seen predominantly in patients under 40 years old. These results suggest that the induction of ovarian failure is a potential mechanism for the observed effect of adjuvant chemotherapy in these patients. The difference in the ovarian failure rates between groups may be a possible explanation for the inferiority of the 12 week regimen. PMID- 1445741 TI - Early stage Hodgkin's disease: ten-year results of a non-randomised study with radiotherapy alone or combined with MOPP. AB - From September 1976 to June 1982, 201 consecutive patients with stage I (A and B) IIA Hodgkin's disease were stratified in two groups according to prognostic factors. The F group included 116 patients with favourable presentation: they were staged with laparotomy and treated with subtotal or total nodal radiotherapy alone. The U group included 85 cases with unfavourable presentation who were staged by laparoscopy and treated with 3MOPP (mechlorethamine, vincristine, procarbazine, prednisone)-radiotherapy-3MOPP. At 10 years the F group showed a freedom from progression (FFP) of 71% with significant difference between stage I and II (85% vs. 59%; P = 0.003) and an overall survival of 84%. The results of the U group were: FFP 83%, overall survival 74%, and the findings were not influenced by stage. FFP in patients with bulky vs. not bulky lymphoma was 70% vs. 87% (P = 0.04). No secondary acute non-lymphocytic leukaemia developed among patients treated with radiotherapy and in continuous complete remission, while acute leukaemia occurred in the F group patients who received salvage chemotherapy (4 of 31 cases) and in the U group (3 of 85 cases). Present results confirm the usefulness of radiotherapy alone in favourable pathological stage IA. All other disease stages will require a different strategy that should consist of radiotherapy combined with short-term effective regimens, such as ABVD (doxorubicin, bleomycin, vinblastine and decarbazine) or VBM (vinblastine, bleomycin and methotrexate) to reduce the incidence of MOPP-associated gonadal dysfunction and leukaemogenesis. PMID- 1445742 TI - Prognosis of lymphoma from a fine-needle aspirate. AB - The prognostic value of S-phase fraction (SPF) determined by flow cytometry from a fine-needle aspirate was investigated in a prospective series of 52 non-Hodgkin lymphomas. The aspirates were drawn either at diagnosis (n = 16) or at lymphoma recurrence (n = 36). Patients with lymphoma with a large SPF (> 10%, n = 24) had only a 21% 3-year survival rate corrected for intercurrent deaths as calculated from the date of aspiration, whereas a smaller SPF was associated with a 71% 3 year survival rate (n = 28, P = 0.0009). SPF size also correlated with Working Formulation grading (P = 0.002). In a multivariate analysis the relative risk of death from lymphomas with a large SPF was 4.01 (1.60-10.1), whereas histological grading, age, and sex had no additional independent prognostic value. SPF determined from a fine needle aspirate had unexpectedly good prognostic value, and the result suggests that the method is of clinical importance. PMID- 1445743 TI - Anticancer drug screening and discovery in the 1990s: a European perspective. PMID- 1445744 TI - A pilot study of intensive cyclophosphamide, epirubicin and fluorouracil in patients with axillary node positive or locally advanced breast cancer. AB - A multicentre pilot study has been conducted to determine an intensive regimen of cyclophosphamide, epirubicin, and fluorouracil which was tolerable and acceptable to patients with node positive breast cancer. Consecutive patients with operable axillary node positive breast cancer (T1-3, N1-2, M0), 266 patients, or locally advanced breast cancer (T4), 22 patients, were treated with cyclophosphamide post operatively for 14 days and epirubicin and fluorouracil, both intravenously on days 1 and 8. Each cycle was repeated monthly for 6 months. Dosages were increased according to predetermined guidelines. Outcome measures were admission to hospital for febrile neutropenia and change in cardiac function as assessed by radionuclide angiography. The first 46 patients were treated at the doses of cyclophosphamide = 75 mg/m2, epirubicin = 50 mg/m2, fluorouracil = 375 mg/m2 (level 1), then 42 patients at cyclophosphamide = 75 mg/m2, epirubicin = 50 mg/m2 and fluorouracil = 500 mg/m2 (level 2), 69 patients at cyclophosphamide = 75 mg/m2, epirubicin = 60 mg/m2, and fluorouracil = 500 mg/m2 (level 3), and 42 patients at cyclophosphamide = 75 mg/m2, epirubicin = 70 mg/m2, and fluorouracil = 500 mg/m2 with concurrent antibiotics (level 4). The rates of febrile neutropenia were 8.7% (level 1), 7.1% (level 2), 18.8% (level 3), and 31% (level 4), respectively, P = 0.002. Accrual to level 4 was discontinued according to study guidelines and a further 89 patients were recruited at level 3 dosages with antibiotic prophylaxis (level 3a), resulting in a 5.6% rate of febrile neutropenia. The difference in febrile neutropenia rates between levels 3 and 3a was statistically significant. There were no toxic deaths and 2 cases of heart failure. In conclusion, through a careful dose-finding study in patients with operable or locally advanced breast cancer, an intensive epirubicin-containing adjuvant regimen has been established which is presently being compared with standard CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy in a randomised trial. In addition, this study suggests that antibiotic prophylaxis reduces the risk of febrile neutropenia in breast cancer patients receiving intensive chemotherapy. PMID- 1445745 TI - Prognostic importance of various clinicopathological features in papillary thyroid carcinoma. AB - The influence of various pathological features on tumour recurrences and cancer deaths has been studied in 173 consecutive cases of surgically treated papillary thyroid carcinoma recorded in 1971-1985. During the follow-up (median 7.3 years), 18.6% of the 161 radically treated patients had recurrent disease, and 8.7% died of thyroid cancer. In the univariate life-table analysis, recurrence-free survival was significantly related to age, pTNM category, tumour size, presence of certain growth patterns, tumour necrosis, tumour infiltration in surrounding thyroid tissue and thyroid gland capsule, lymph node metastases, presence of extra-nodal tumour growth and number of positive lymph nodes, whereas only tumour diameter, thyroid gland capsular infiltration and presence of extra-nodal tumour growth remained as significant prognostic factors in the multivariate analysis. Regarding thyroid cancer deaths, sex, age, pTNM category, radicality of surgical treatment, tumour diameter, macroscopic appearance, cellular atypia, tumour necrosis, thyroid gland capsular infiltration, vascular invasion, extra-thyroidal extension and lymph node metastases were all significant variables in the univariate analysis. However, only sex, age, radicality of surgical treatment and vascular invasion were found to be significant predictors of thyroid cancer deaths in the final multivariate Cox model, whereas cellular atypia and necrosis showed a borderline significance. Our study thus documents the independent importance of certain histological features for morbidity and mortality in surgically treated cases of papillary thyroid cancer. PMID- 1445746 TI - Treatment of melphalan-resistant multiple myeloma with vincristine, BCNU, doxorubicin, and high-dose dexamethasone (VBAD). AB - A total of 65 patients (35 male/30 female) with multiple myeloma primarily (33) or secondarily (32) resistant to melphalan and prednisone were treated with vincristine, carmustine (BCNU), doxorubicin, and high-dose dexamethasone (VBAD) at 4-week intervals. Among 60 evaluable patients the overall response was 36.6% (21.6% objective response plus 15% improvements). The response rate was significantly higher in primarily resistant patients than in those becoming resistant after a prior response (48.4 vs. 24.1%, P < 0.05). The median duration of response was 17.5 months. When survival of responders and non-responders were compared by the conventional method, a highly significant difference was observed (P < 0.001). However, using the Mantel and Byar procedure and the landmark method, only a trend for longer survival in the responders was registered. These results indicate that although VBAD is effective in at least one third of patients with advanced multiple myeloma resistant to melphalan, its impact on survival is limited. PMID- 1445747 TI - Prediction of superficial bladder cancer by nuclear image analysis. AB - A cohort of 270 superficial transitional cell bladder tumours (Ta-T1) was followed-up for over 8 years. WHO grade, papillary status and six nuclear factors were related to progression, recurrence-free survival (RFS) and bladder cancer related survival (BS) during the follow-up period. Mean nuclear area (NA), standard deviation of nuclear area (SDNA), nuclear perimetry (PE), standard deviation of nuclear perimetry (SDPE), shortest nuclear axis (Dmin) and longest nuclear axis (Dmax) were significantly related to WHO grade and papillary status (P < 0.0001). All the nuclear factors were related significantly to progression in univariate analysis (P < 0.01) whereas in a multivariate analysis WHO grade (P < 0.0001) and papillary status (P = 0.048) included independent prognostic information. RFS was related to PE (P = 0.009), SDPE (P = 0.013), Dmin (P = 0.021), Dmax (P = 0.028) and SDNA (P = 0.029). In papillary tumours SDPE (P = 0.007) and Dmin (P = 0.024) predicted RFS. BS was related to WHO grade, papillary status, NA, SDNA, PE, Dmax, Dmin (all P < 0.0001) and to SDPE (P = 0.003). In papillary tumours PE (P < 0.0001), Dmax (P = 0.0022), Dmin (P = 0.0027), WHO grade (P = 0.0036), NA (P = 0.0005), SDNA (P = 0.0355) and SDPE (P = 0.0718) predicted BS. In multivariate analysis SDPE (P = 0.029) predicted RFS and survival was related to WHO grade (P < 0.001) and PE (P = 0.014) independently. In papillary tumours only Dmax (P = 0.001) predicted survival independently. The results show that superficial papillary transitional cell bladder tumours can be efficiently categorised into prognostic groups by nuclear image analysis and the results provide a new classification system for superficial papillary bladder tumours. Tumours with high nuclear factor values should be considered for radical primary therapy and adjuvant therapy after transurethral resections. PMID- 1445748 TI - Tissue polypeptide antigen in breast cancer cytosol: a new effective prognostic indicator. AB - Since 1982 we have been evaluating oestrogen and progesterone receptors (PgR), cathepsin D and the cytosolic levels of the tumour marker, tissue polypeptide antigen (TPA), in 257 patients radically resected for breast cancer (follow-up 24 81 months). TPA was measured by an immunoradiometric assay previously validated for cytosol. No significant associations were found between cytosolic TPA and age, tumour size, lymph-node status, receptor status and cathepsin D. TPA+ cases showed a significantly longer disease-free survival (DFS) and overall survival (OS) than TPA-patients (log-rank P < 0.0001). The prognostic value of cytosolic TPA was also demonstrated after stratification by nodal status, PgR and cathepsin D. The prognostic value of TPA was independent of the other prognostic indicators, being the most powerful among the evaluated indices (Cox multivariate analysis: chi 2 15.5 for DFS, 11.4 for OS). We conclude that cytosolic TPA is a powerful additional prognostic factor in primary breast cancer. Its prognostic role should therefore be extensively evaluated. PMID- 1445749 TI - Tumour infiltrating lymphocytes as an independent prognostic factor in transitional cell bladder cancer. AB - The prognostic value of tumour infiltrating lymphocytes (TIL) was assessed in a cohort of 514 patients with a transitional cell bladder cancer (TCC) during a follow up period of over 9 years. The density of TIL were positively correlated to WHO grade (P < 0.0001), non-papillary growth architecture (P < 0.0001), morphometric nuclear factors (P < 0.007) and volume corrected mitotic index (M/V index) (P < 0.0001). Dense TIL predicted progression in Ta-T1 tumours (P < 0.0006) whereas in a multivariate analysis they had no independent predictive value. Dense TIL were related to short recurrence-free survival in Ta-T1 tumours in a univariate analysis (P = 0.06) as well as in a multivariate analysis (P = 0.005). Dense TIL predicted unfavourable prognosis in the entire cohort (P = 0.0316) and in papillary tumours (P = 0.062) whereas in nodular tumours TIL were a sign of good prognosis (P = 0.0141). Also in T3-T4 tumours TIL were related to less aggressive behaviour of TCC (P = 0.0259). In a multivariate analysis including clinical stage (T-category), WHO grade, papillary status, six morphometric nuclear factors and M/V index dense TIL were a highly significant indicator of a favourable prognosis (P = 0.007). Particularly TIL categorized rapidly proliferating TCC into prognostic groups (P = 0.001). The results show that TIL are a sign of efficient host defence mechanisms in TCC and TIL predict a favourable prognosis in invasive TCC. PMID- 1445750 TI - Relations between epidermal growth factor receptor and oestrogen and progesterone receptors in breast cancers of premenopausal and postmenopausal patients in Kuwait. AB - The levels of cell membrane epidermal growth factor receptor EGFR and cytosol (c) and nuclear (n), oestrogen (E) and progesterone (P) receptors (R) were determined in 132 specimens of primary breast cancers. In the tumours of postmenopausal women an inverse significant correlation was demonstrated between the concentrations of EGFR vs. ERc, ERn, and PRc while no such correlation was noted in the tumours of premenopausal women. Premenopausal and postmenopausal EGFR positive tumours (> or = 10 fmol/mg membrane protein) could be regarded as homogenous with respect to the concentration of ER and PR whose mean values were low and without being significantly different. EGFR negative tumours were heterogeneous with respect to the ER and PR concentrations. Postmenopausal EGFR negative (< 10 fmol/mg membrane protein) tumours had evidently higher mean values of ER and PR than premenopausal EGFR negative tumours, but these differences were statistically significant for oestrogen receptors only. The levels of ER and PR of premenopausal EGFR negative tumours were approximated to the corresponding levels of EGFR positive tumours. PMID- 1445751 TI - Childhood leukaemia following the Chernobyl accident: the European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS). AB - The objective of the European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) is to investigate trends in incidence rates of childhood leukaemia and lymphoma in Europe, in relation to the exposure to radiation which resulted from the accident at the Chernobyl nuclear power plant in April 1986. In this first report, the incidence of leukaemia in children aged 0-14 is presented from cancer registries in 20 European countries for the period 1980-1988. Risk of leukaemia in 1987-1988 (8-32 months post-accident) relative to that before 1986, is compared with estimated average dose of radiation received by the population in 30 geographic areas. The observed changes in incidence do not relate to exposure. The period of follow-up is so far rather brief, and the study is planned to continue for at least 10 years. PMID- 1445752 TI - In vitro and in vivo antitumoral activity of alkylphosphonates. AB - Hexadecylphosphocholine is a new antitumour agent with a highly selective activity in chemically induced mammary tumours. It was suggested, that hexadecylphosphocholine is a pro-drug, cleavable by phospholipases C and/or D, creating hexadecanol or hexadecylphosphate as the active principle. To test this hypothesis, the antineoplastic activity of three alkylphosphonates, cleavable either by phospholipase C or D, are compared with those of the parent compound, hexadecylphosphocholine. Cell culture experiments, in which radiolabelled alkylphosphonates were incubated with a neoplastic cell line, showed no metabolism even after 3 days of incubation. In in vivo experiments with dimethylbenzanthracene-induced rat mammary carcinomas, all three alkylphosphonates showed antineoplastic activity, although none of them reached the high activity of hexadecylphosphocholine. These results indicate that the antitumoral activity of alkylphosphocholines and alkyl lysophosphatidylcholines is due to direct toxicity and not dependent on metabolism by phospholipases C or D or related enzymes. PMID- 1445753 TI - Influence of aw value and storage temperature on the multiplication and enterotoxin formation of staphylococci in dry-cured raw hams. AB - Growth and enterotoxin A production in dry-cured raw ham, with different aw and pH values, was investigated for Staphylococcus aureus strain FRJ-100 over a temperature range of 20-35 degrees C when stored for up to 7 days. Enterotoxin production took place at all temperatures tested in the meat of ham that was cured, but not dried (aw 0.95). In dry-cured raw ham with an aw-value of about 0.92, and stored at 20 degrees C, no enterotoxin production was detectable within the 7-day storage period, whereas enterotoxin was produced at the higher temperatures. In ham with an aw of about 0.89, enterotoxin was produced only when stored for 7 days at 35 degrees C. Critical points for S. aureus multiplication and enterotoxin-formation during production and storage of dry-cured raw ham are discussed. PMID- 1445754 TI - Detection of Clostridium botulinum in natural sweetening. AB - Various sugar products were examined for contamination with C. botulinum spores. Type A, B and C spores were detected in three of 56 samples of sugar for apiculture, which may attest the significance of bee-feed as a source of contamination of honey. The heavy contamination of honey with C. botulinum spores sometimes encountered, however, can not be explained unless some other factors, e.g., that allowing germination and multiplication of the spores somewhere during honey production, are found. Type A spores were detected in some samples of raw sugar and molasses and also in two of 41 samples of brown sugar lump, but not in refined sugar or other various samples taken at a sugar factory or in sugar cane left on the field in Okinawa. The fact that some natural sweetenings are contaminated with C. botulinum spores, even in low concentrations, may be food hygienically important. PMID- 1445755 TI - Fungi causing thread mould spoilage of vacuum packaged Cheddar cheese during maturation. AB - Thread mould is a defect which occurs sporadically in maturing vacuum packaged Cheddar cheese, caused by the growth of fungi in folds and wrinkles of the plastic film in which the cheese is packaged. Fungi were isolated and identified from 110 Cheddar cheese blocks exhibiting typical thread mould defects. The major causative species were found to be Cladosporium cladosporioides, Penicillium commune, C. herbarum, P. glabrum and a Phoma species. Yeasts were also frequently isolated from the cheese, the majority belonging to the genus Candida. Fungal species which can cause thread mould defects were also found in the cheese factory environment, on cheesemaking equipment, in air, and in curd and whey, providing a wide range of potential sources of contamination. PMID- 1445756 TI - Variation in growth kinetics and phenotype of Aeromonas spp. from clinical, meat processing and fleshfood sources. AB - Sixty-four strains of motile aeromonads (A. hydrophila, A. sobria and A. caviae), isolated from clinical meat processing and ready-to-eat fleshfood sources, and the A. hydrophila type strain were tested with respect to their growth kinetics at 4 degrees C and 37 degrees C, and the reported indicators of pathogenicity: autoagglutination and haemolysis (tested using a CAMP reaction). Between the species, A. caviae grew the fastest at 37 degrees C and had the highest percentage of strains not able to grow at 4 degrees C (after 200 h incubation). Within the species, food-derived strains of A. hydrophila were better adapted to growth at lower temperatures than those from clinical or meat processing sources. Clinical strains of A. hydrophila autoagglutinated more frequently than those from other sources, but not differences in CAMP reactions were noted. Aeromonas caviae and A. sobria isolates appeared to be homogeneous with respect to growth kinetics at the temperatures tested. A comparison of the growth kinetics of the A. hydrophila type strain and a food-derived A. hydrophila strain clearly reflected the latter's enhanced ability to grow at low temperatures. PMID- 1445757 TI - Identification and characterization of two bacteriocin-producing strains of Lactococcus lactis isolated from vegetables. AB - Isolated from mixed salad and fermented carrots, 123 strains of lactic acid bacteria were screened for bacteriocin production. Two strains, D53 and 23, identified as Lactococcus lactis by DNA-DNA hybridizations, produced heat stable bacteriocins which were resistant to trypsin and pepsin, but were inactivated by alpha-chymotrypsin and proteinase K. The bacteriocins were active from pH 2 to 9 and inhibited species of Listeria, Lactobacillus, Lactococcus, Pediococcus, Leuconostoc, Carnobacterium, Bacillus and Staphylococcus. Strain D53 produced bacteriocin at pH values of 4.5-8.0 and from 10 to 37 degrees C. PMID- 1445758 TI - Incidence of Listeria monocytogenes in fresh foods in Barcelona (Spain). AB - From September 1989 to March 1990, a study of Listeria spp. was carried out on 311 samples of raw foodstuffs from markets and other establishments in the city of Barcelona. These foodstuffs included vegetables (103 samples), minced meats from pork, beef and poultry (168 samples) and bivalve molluscs (40 samples). L. monocytogenes was isolated in 7.8% of the vegetable samples, 17.3% of the minced meats and in 7.5% of bivalve molluscs. The most frequent serovars were 1/2 and 4. Other species isolated were L. innocua, L. welschimeri and L. seeligeri. PMID- 1445759 TI - The incidence of Listeria species in retail foods in Japan. AB - Meat, fish and vegetable products obtained at retail shops in or around Tokyo were examined for Listeria contamination. Listeria spp. were isolated from 43 (56.6%) out of 76 samples of meat products. L. monocytogenes occurred in 26 (34%) of the samples, L. monocytogenes was isolated from 7 (6.1%) out of 114 samples of fish and fish products including 'ready-to-eat' foods. Listeria was not isolated from any of 21 samples of vegetable and vegetable product including 'ready-to eat' foods investigated. PMID- 1445760 TI - The ability of the ropy slime-producing lactic acid bacteria to form ropy colonies on different culture media and at different incubation temperatures and atmospheres. AB - The ability of the ropy slime-producing lactic acid bacteria to form ropy colonies aerobically and anaerobically on APT, MRS, MRS-S and Rogosa SL agars at 15, 20 and 30 degrees C was tested. Wide variation was observed in the proportion of ropy colonies produced with different culture methods and different test periods. The percentage of viscous colonies was usually highest at 15 degrees C. No suitable uniform method for all strains was found; and the results varied according to the bacterial strain studied. For testing purposes, use of the method producing the highest proportion of ropy colonies for each bacterial strain is recommended. PMID- 1445761 TI - Classification of ropy slime-producing lactic acid bacteria based on DNA-DNA homology, and identification of Lactobacillus sake and Leuconostoc amelibiosum as dominant spoilage organisms in meat products. AB - The classification of lactic acid bacteria able to cause ropy slime on vacuum packed cooked meat products was carried out based on DNA-DNA homology. The ropy slime-producing lactobacilli were identified as strains of Lactobacillus sake and the ropy slime-producing leuconostocs, such as Leuconostoc amelibiosum and Leuconostoc mesenteroides. PMID- 1445762 TI - Decontamination with lactic acid/sodium lactate buffer in combination with modified atmosphere packaging effects on the shelf life of fresh poultry. AB - The effect of the treatment with various concentrations (2%, 5%, 7.5% and 10% w/v) of lactic acid/sodium lactate buffer (pH 3.0) combined with modified atmosphere packaging (MAP) (90% CO2/10% O2) on the shelf life and organoleptic quality of fresh chicken legs stored at 6 degrees C was investigated. The CO2 concentration of all samples packed in modified atmosphere (MA) decreased during the first 3 days of storage, followed by a gradual increase after the third day, while O2 showed a corresponding decrease. The buffering capacity of the buffer systems seem to be sufficient to maintain a low pH of the skin during storage. Legs treated with 2, 5, 7.5, and 10% (w/v) lactic acid/sodium lactate buffer (pH 3.0) combined with MAP have a shelf life at 6 degrees C of 14, 15, 16 and 17 days, respectively. The shelf life when the product was not treated with lactic acid was 1, 2.3 and 4 days shorter, respectively. PMID- 1445763 TI - Incidence and coincidence of Listeria spp., motile aeromonads and Yersinia enterocolitica on ready-to-eat fleshfoods. AB - A survey for the presence of Listeria spp., Yersinia enterocolitica and motile aeromonads in 203 samples of ready-to-eat fleshfoods purchased from retail outlets was conducted. Overall, 39.4%, 3.4% and 23.2% of samples were positive for the presence of Listeria spp., Y. enterocolitica and motile aeromonads respectively. Two factors have been identified as contributing to contamination of fleshfoods by these cold-tolerant bacteria. These are (i) the method of sale; delicatessen-bought foods were notably more contaminated than similar products bought pre-packaged, and (ii) the method of preservation. For motile aeromonads fermented foods were the least contaminated, whereas smoked and cooked products had similar incidence rates. For L. monocytogenes, significantly more (41.9%) smoked products were contaminated than fleshfoods preserved by other methods. For Y. enterocolitica, only cooked products were contaminated. In the case of cooked fleshfoods it must be assumed that most contamination occurs post-cooking and that contamination rates are increased by poor food handling procedures. Of the three possible pairwise combinations of these organisms, the coincidence of Y. enterocolitica and motile aeromonads was the only one that differed significantly from a random distribution (P less than 0.001), indicating that fleshfoods contaminated with Y. enterocolitica are probably also contaminated by motile aeromonads. PMID- 1445764 TI - Is any strain of Listeria monocytogenes detected in food a health risk? AB - Listeria spp. have been isolated from various food items. This fact does not mean in any case a true health risk. A balanced appraisal should be based on quantitative as well as qualitative aspects. Actually, there is still an open debate whether a limited number of Listeria has to be tolerated at least in certain food items. In addition, the pathogenic potency of an isolate may be put into account. Pathogenicity of various Listeria spp. definitely varies. Most Listeria spp., except Listeria monocytogenes, can be regarded as harmless to man. Also, not all strains of L. monocytogenes are pathogenic: rough variants possess only reduced virulence; non-hemolytic mutants have completely lost their pathogenic potency. Furthermore, several other virulence factors may be lost under natural conditions, so that among the majority of hemolytic, pathogenic isolates there may be others which are non-pathogenic or of low virulence only. Unfortunately, these strains actually cannot be recognized and characterized by common laboratory tests, so that animal pathogenicity seems to be the only way to get a final conclusion on the health risk of an isolate of L. monocytogenes from any food. The problem raised by this is which animal test is able to predict a true health risk either for normal hosts or for immunocompromised patients? PMID- 1445765 TI - Characterization and partial purification of a bacteriocin produced by Leuconostoc carnosum LA44A. AB - Twenty Leuconostoc strains isolated from vacuum packaged Vienna-type sausages were screened for antagonistic activity against various Gram-positive organisms (including Listeria spp.). One of the three strains exhibiting inhibitory activity was chosen for further investigation. This strain was identified as Leuc. carnosum and the inhibitory substance produced was named carnosin. Carnosin was inactivated by trypsin but not by catalase or other non-proteolytic enzymes tested. Carnosin retained activity after heating at 100 degrees C for 20 min, whereas heating at 121 degrees C for 15 min resulted in complete loss of activity. Carnosin was active at pH values ranging from 2 to 9. Carnosin activity was not detectable until cells were in the late log-phase of growth. At low temperatures (4 degrees C), higher cell densities were required before carnosin activity could be detected. Carnosin was active against various lactic acid bacteria, Enterococcus faecalis and Enterococcus faecium and against Listeria spp. Difficulties in purification were reduced by growing Leuc. carnosum in a modified MRS medium, having 50% of the normal peptone concentration and no Tween or meat extract. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of partially purified carnosin indicated that it has a molecular mass between 2510 and 6000 Da. Yet, retention of activity after exhaustive dialysis suggested a molecular mass > 14kDa. It is hypothesized that carnosin forms large active complexes which can be dissociated to small (active) components. PMID- 1445766 TI - Evaluation of the MPN, Anderson-Baird-Parker, Petrifilm E. coli and Fluorocult ECD method for enumeration of Escherichia coli in foods of animal origin. AB - Commercially available beta-D-glucuronidase (GUR) based methods, Petrifilm E. coli (PEC) and Fluorocult ECD (FECD), and ISO standard MPN and Anderson-Baird Parker (ABP) procedures were evaluated for routine enumeration of E. coli in naturally contaminated foods of animal origin. The methods concerned were classifiable in a sequence of best qualities for: production, MPN > ABP = PEC = FECD; costs, FECD > ABP = PEC > MPN; time per measurement, ABP = PEC = FECD > MPN; practical use, PEC > FECD > ABP > MPN; detection at low contamination, MPN > ABP = PEC > FECD. The ABP and PEC method appeared useful for routine counting of E. coli in raw meat, poultry and meat products, whereas the MPN procedure turned out to be more sensitive, however, impractical and considerably more expensive. The FECD method was inexpensive although suitable for the enumeration of E. coli at higher contamination level (> 50 cfu/g). The indole and MUG indicators both applied to demonstrate E. coli with the ABP or FECD method proved to be equal in specificity. PMID- 1445767 TI - Heat-resistant fungi in the soil. AB - The occurrence of heat-resistant fungi has been demonstrated in samples of soil from the Slovak Republic. The heat-resistant species isolated were Byssochlamys nivea, Dichotomomyces cejpii, Eupenicillium baarnense, Neosartorya fischeri, Talaromyces avellaneus, Tal. bacillisporus, Tal. emersonii, Tal. flavus, Tal. trachyspermus, Tal. wortmanii, Botryotrichum piluliferum, Gilmaniella humicola and Nodulisporium sp. Some of them were isolated for the first time from Czechoslovakian soil. For the various soil samples examined, the occurrence of heat-resistant fungi varied qualitatively and quantitatively. Further research is needed to identify conditions affecting the occurrence of heat-resistant fungi in soil. PMID- 1445768 TI - Sakacin M, a bacteriocin-like substance from Lactobacillus sake 148. AB - The antagonistic activity of Lactobacillus sake 148 was evaluated during its growth on complex broth media and in a semisynthetic defined medium (SDM) with various supplements. The antagonistic activity was a growth-associated property, being detected and quantified when L. sake 148 was grown at either 4, 8, 16, 25 or 32 degrees C. The concentrated culture supernatant of L. sake 148 was subjected to purification by lyophilization and gel filtration. The purification procedure resulted in a small increase in its specific activity (7-fold) and in a low recovery of the original inhibitory activity (8%). Gel filtration analysis of the partially purified activity on Sephadex G-50 revealed an apparent molecular weight of 4640. The partially purified antagonistic activity of L. sake 148 was destroyed by treatment with proteolytic enzymes. However, the antagonistic activity was resistant to heat, having D-values at 121, 135 and 150 degrees C of 23.8, 17.4 and 15.2 min, respectively. PMID- 1445769 TI - Is thermotolerance correlated to heat-shock protein synthesis in Lactococcus lactis subsp. lactis? AB - Exposure of Lactococcus lactis subsp. lactis cells to a heat shock at 40 degrees C for 30 min induces thermotolerance, the increased ability of bacterial cells to survive exposure to lethal temperature (52 degrees C for 25 min). This transient state of thermal resistance is accompanied, as in Escherichia coli, by the synthesis of a new set of specific proteins termed heat-shock proteins (Hsps). Pre-treatment of the bacterial cells by antibiotics (streptomycin, spiramycin, kanamycin and erythromycin) known to act on translation, induces the major Hsps synthesis but no thermal protection; conversely, puromycin and amino acid analogues treatments, known to produce abnormal and incomplete peptides, triggers the thermotolerance state without inducing significant Hsps synthesis. These results demonstrate that heat-shock response and induced thermotolerance are not tightly correlated phenomena in L. lactis subsp. lactis. PMID- 1445770 TI - Mycological condition of maize products. AB - Maize and maize-related products were investigated in a collaborative study for viable moulds and antigenic extracellular polysaccharides (EPS) produced by Aspergillus and Penicillium species. In addition, the samples were tested for the presence of aflatoxin B1. All maize products, with the exception of the heat processed products, contained viable moulds on an average of (log10 values) 3.3 +/- 0.7 colony-forming units per gram. In most samples a mixed mould flora was present. Species of the genus Fusarium were dominant, followed by Aspergillus, Eurotium and Penicillium. The mould colony count correlated positively with the presence of antigenic extracellular polysaccharides produced by species of Aspergillus and Penicillium. Gamma irradiation did not affect the detection of antigenic extracellular polysaccharides. Aflatoxin B1 was detected in two out of 35 samples; these contained 0.6 and 0.8 microgram/kg. From one of these aflatoxin B1-containing samples, Aspergillus flavus was isolated. PMID- 1445771 TI - Differentiation of Listeria monocytogenes isolates by using plasmid profiling and multilocus enzyme electrophoresis. AB - Three hundred and seven Listeria monocytogenes isolates from various origins (clinical sources, raw chicken, seafoods, dairy and meat products and processing environments) were screened for plasmids. The overall frequency of L. monocytogenes isolates containing plasmids was 77%. The highest percentages of plasmid positive isolates were found from meat (89%), chicken (81%) and dairy products (64%), while clinical isolates had the lowest plasmid percentage (28%). Seven sizes of plasmids (21, 24, 27, 35, 40, 47 and 52 MDa) were distinguished. All sizes were represented in the meat isolates, clinical isolates contained only two of the plasmid sizes, while several different sizes of plasmids were found in the isolates from other origins. Plasmid profiling divided the isolates into ten plasmid pattern types. Multilocus enzyme electrophoresis of 75 isolates demonstrated 12 distinctive multilocus genotypes (ETs) which clustered into two groups: cluster A including serotype 1 and 4 isolates, and isolates not typable by Difco antisera serotype 1 and 4, and cluster B containing only serotype 1 isolates. No relationship between ETs and plasmid profiles could be demonstrated. PMID- 1445772 TI - Removal of Yersinia enterocolitica from fresh parsley by washing with acetic acid or vinegar. AB - Different washing procedures and solutions were applied to fresh parsley and the effect on artificially contaminated Y. enterocolitica and the natural population of aerobic bacteria was determined. Dipping the parsley containing 10(7) Y. enterocolitica per gram into the 2% (v/v) acetic acid or 40% (v/v) vinegar solutions for 15 min exerted pronounced bactericidal effect against this organism. No viable aerobic bacteria were recovered after 30 min dip in 5% (v/v) acetic acid, whereas vinegar led to 3-6 log10 cycles decrease in the number of aerobic bacteria depending on vinegar concentration and holding time. PMID- 1445773 TI - Impedance detection of Salmonella in processed animal protein and meat. AB - The impedance technique showed a detection rate (95%) equal to that of conventional enrichment for raw meat contaminated with Salmonella. For processed animal protein samples impedance was less sensitive. A commercially available Easter and Gibson impedance medium used for the selective enrichment of salmonellae proved superior to the laboratory prepared equivalent for the detection of Salmonella in processed animal protein. The rate of false-positive results with the impedance technique was high. PMID- 1445774 TI - ABMT shows no benefits for three high-risk cancers. PMID- 1445775 TI - Gene mapping may yield insights into breast cancer development. PMID- 1445776 TI - Cell therapy may be useful in BMT, HIV, and kidney cancer. PMID- 1445777 TI - Pros and cons of fluoxetine for the depressed cancer patient. AB - When major depression develops in patients with cancer, specific antidepressant treatment should be initiated. Fluoxetine (Prozac) is one of several effective treatments for depression; it is currently the most frequently prescribed antidepressant in the United States. Unfortunately, the information from studies and reports regarding the use of fluoxetine in patients with cancer is limited. This article reviews the properties, drug interactions, and side-effect profiles of fluoxetine and the other antidepressants most relevant to the care of cancer patients. Also discussed are strategies for the prudent prescription of fluoxetine, the tricyclic antidepressants, and the psychostimulants in depressed cancer patients. PMID- 1445778 TI - The human genome project and clinical medicine. AB - Genetic research has already begun to pay clinical dividends, as investigators have successfully isolated disease genes, including those responsible for Duchenne muscular dystrophy, cystic fibrosis, and the fragile X syndrome. This last disorder appears to be associated with the progressive amplification of a short, repeated DNA sequence, a mechanism that may also occur at other cytogenetically fragile sites and in other genetic disorders or neoplasias. This article reviews genetic mapping techniques being used by the Human Genome Project, methods for identifying disease genes, and clinical applications. It also includes discussions of mutation detection, diagnosis, and gene therapy. PMID- 1445779 TI - Adjuvant therapy of rectal cancer. AB - The treatment of rectal cancer has gradually evolved based on our knowledge of the failure patterns. Although results with surgery alone are good in patients with disease limited to the bowel wall and with no lymph node spread, surgery alone is less effective for more advanced disease. Treatment strategies that combine pelvic radiation therapy and 5-fluorouracil-based chemotherapy regimens have significantly improved local recurrence rates and overall survival results for patients with disease extending through the bowel wall or those with positive lymph nodes. Recent studies suggest that methyl CCNU can be dropped from chemotherapy regimens without loss of efficacy. Newer strategies being investigated include modulations of 5-fluorouracil with agents such as leucovorin and levamisole, possibly in combination, and continuous infusions of 5 fluorouracil. PMID- 1445780 TI - Isolation and characterization of cDNA encoding a spicule matrix protein in Hemicentrotus pulcherrimus micromeres. AB - A cDNA clone, termed pHPSMC, was obtained from the Japanese sea urchin Hemicentrotus pulcherrimus, and it was found to be highly homologous in sequence to the spicule matrix protein cDNA of Strongylocentrotus purpuratus (Sucov et al., Dev. Biol. 120: 507-519, 1987). During early embryogenesis, mRNA complementary to pHPSMC appeared in gastrulae and remained at a similar level until the pluteus stage. In situ hybridization revealed that the mRNA was localized exclusively in primary mesenchyme cells in gastrulae. pHPSMC mRNA was detected in micromeres in vitro after 48 h of culture, but it was not found in blastomeres immediately after isolation. These features suggested that pHPSMC represents the spicule matrix protein cDNA cognate in Hemicentrotus pulcherrimus. In the derived polypeptide, we detected a domain containing a tandemly repeated 13-amino acid sequence as did Sucov et al. (1987). Unexpectedly, the sequence of the repeated element was completely different from that originally reported for Strongylocentrotus purpuratus, but it was very similar to the corrected sequence that appeared recently. PMID- 1445781 TI - Hydrocortisone perturbs the cell proliferation pattern during feather morphogenesis: evidence for disturbance of cephalocaudal orientation. AB - In this study, we have monitored the spatial distribution of S-phase cells during successive stages of normal feather morphogenesis using the specific marker BrdU. We also disturbed the development program by administration of hydrocortisone on the chorioallantoic membrane of 6.5-day chick embryos and examined the resulting pattern of BrdU incorporation. Our results show that a specific spatio-temporal pattern of cell proliferation occurs during successive stages of feather development and that this pattern accounts for the growth of feather buds according to the cephalocaudal orientation. Our experimental analysis showed that the stage-dependent alteration of feather morphogenesis (as shown by Zust, Ann. Embryol. Morphogen. 4, 1971 and confirmed by Demarchez et al., Dev. Biol. 106, 1984), is based on a stage-dependent alteration of the proliferation pattern in the epidermis. Forty-eight hours after treatment, non-induced epidermis ceases DNA synthesis and is unable to form placodes. Induced epidermis at the placodal and dermal condensation stages fails to produce the cohorts of S-phase cells responsible for the caudal outgrowth and the slanting shape of the buds. These young buds display anarchic proliferation in the whole epidermis possibly resulting in the appearance of "curly" feathers. Together, these results show the importance of the spatial pattern of ectodermal and mesodermal cell proliferation during the normal feather morphogenesis. Moreover, they corroborate the particular role of epidermis both in the establishment of feather rudiments and in the cephalocaudal orientation of the feathers. PMID- 1445782 TI - Purification and localization of p10, a novel protein that increases in nymphal regenerating legs of Periplaneta americana (American cockroach). AB - Content of a protein with a molecular mass of 10 kDa (p10) was found to increase significantly in regenerating legs of the American cockroach (Periplaneta americana). This protein was purified to homogeneity from a homogenate of regenerating legs. Partial amino acid sequencing indicated that p10 is a novel protein. Immunoblotting showed that its content in regenerating legs was 30 times that in normal legs, and decreased significantly when leg regeneration was complete. An immunofluorescence study revealed that p10 localizes exclusively on the external side of newly formed epidermis of regenerating legs. PMID- 1445783 TI - Analysis of a unique molecule responsible for regeneration and stabilization of differentiated state of tissue cells. AB - In Wolffian regeneration in the newt, a functional lens can be regenerated through cellular transdifferentiation of the pigmented epithelium of the mid dorsal marginal iris. A novel monoclonal antibody, 2NI-36 mAb, generated in our laboratory has been utilized as a highly useful probe to study newt lens regeneration. The antigen molecule against this 2NI-36 mAb (2NI-36) became temporarily undetectable only at the site of lens regeneration. Moreover, the ventral iris pieces expressed the ability to differentiate a lens when pretreated with this monoclonal antibody and implanted in lentectomized eyes (Eguchi, Cell Differ. Dev. 25, Suppl., 1988). We have investigated the distribution of 2NI-36 in newt tissues. 2NI-36 was not specific to iris pigmented epithelium and distributed in many different kinds of mesodermal tissues, including dermis, blood vessel, mesonephros and so forth. 2NI-36 was also detected in either cell surface or intercellular spaces of cultured pigmented epithelial cells when they organized an epithelial cell sheet. Western blot analysis showed that 2NI-36 had the molecular weight of 50-200kD and was completely digested by trypsin, suggesting that 2NI-36 was a glycoprotein with many carbohydrate chains. It was also revealed by Western blot analysis that all the tissues in which 2NI-36 could be detected expressed this molecule similar to that in the iris epithelium. We expect that 2NI-36 is a glycoprotein expressed by various newt tissues and is functional to stabilize the differentiated state of each tissue cell in the same way as observed in the iris pigmented epithelial cells. PMID- 1445784 TI - Expression and distribution of regeneration-responsive molecule during normal development of the newt, Cynops pyrrhogaster. AB - We have investigated the expression and distribution of the regeneration responsive molecule, 2NI-36, the loss of which is responsible for initiation of dedifferentiation of dorsal marginal iris pigmented epithelial cells to regenerate a lens. In the process of the normal development of the newt, the expression of 2NI-36 could not be detected in embryos at the early developmental stages, i.e., cleavages, gastrulation and neurulation, nor through later developmental stages to tail-bud, even though organogenesis was occurring. 2NI-36 was not detectable in any tissues until embryos reached developmental stage 40 (before hatching). In hatched larvae around developmental stage 46, strong expression of 2NI-36 was observed in several tissues including the vascular endothelium, the pigmented epithelium and the inner layer of skin epidermis. Moreover, 2NI-36 was present on the cell surface of these tissue cells. In conclusion, when the embryos hatch out to become swimming larvae that can feed by themselves, 2NI-36 begins to be expressed in some kinds of differentiated tissues. These results suggest that the function of 2NI-36 might be related to the completion of morphogenesis in development and also to the stabilization of the differentiated state of newly formed tissue cells. PMID- 1445785 TI - Post-fertilization changes in Discoglossus pictus (Anura) eggs result in the formation of a capsular chamber where the egg rotates. AB - Discoglossus pictus is one of the few anurans with an egg where a capsular chamber forms as a consequence of fertilization; the egg with its vitelline envelope rotates in this chamber according to gravity. We investigated the formation of the capsular chamber through various experimental cytochemical and ultrastructural approaches, and found that it is the product of plug liquefaction. The plug is a lens-shaped jelly coat typical of Discoglossus, and covering only part of the egg animal half. About 15 min after fertilization, granular material coming from the egg enters the plug, which gradually dissolves and, once liquefied, reorganizes itself around the entire egg, thus forming the chamber. This process goes through stages of rearrangement of the 25-A- and 250-A thick filaments which constitute the plug matrix. The material entering the plug derives from the exocytosis of two vacuole types, with electron transparent and granular PAS-positive contents. Liquefaction of the plug correlates with the reduction of disulfide bonds present in its matrix. Furthermore, in vitro tests showed that the substances released from the egg are active in selectively dissolving only the plug, and lose activity upon boiling. PMID- 1445786 TI - Alterations in biosynthetic accumulation of collagen types I and III during growth and morphogenesis of embryonic mouse salivary glands. AB - We examined the biosynthetic patterns of interstitial collagens in mouse embryonic submandibular and sublingual glands cultured in vitro. Rudiments explanted on day 13 of gestation and cultured for 24, 48, and 72 h all synthesized collagen types I, III, and V. However, while the total incorporation of label into collagenous proteins did not change over the three-day culture period, the rate of accumulation of newly synthesized types I and III did change. At 24 h, the ratio of newly synthesized collagen types I:III was approximately 2, whereas at 72 h, the ratio was approximately 5. These data suggest that collagen types I and III may be important in initiation of branching in this organ, but that type I may become dominant in the later stages of development and in maintenance of the adult organ. PMID- 1445787 TI - Relationship between innervation and forelimb regenerative capacity in the postmetamorphic pond frog Rana brevipoda porosa. AB - The limb regenerative capacity and the quantity of innervation (the percentage of a cross-sectional area of amputation forelimb stump occupied by nerves) in the pond frog, Rana brevipoda porosa, was investigated in postmetamorphic froglets and adults of various sizes by means of amputating forelimbs through the zeugopodium. Nearly all the amputated limbs of newly metamorphosed froglets, 18 19 mm in snout-vent length, showed heteromorphic regeneration. However, the larger the body size, the lower the presence of limb regeneration. Limb regenerative capacity was completely lost in froglets and adults with snout-vents larger than 35 mm. The quantity of innervation of limbs was highest in newly metamorphosed froglets, gradually decreasing with growth. The nerve quantity in adults with a snout-vent length between 60-67 mm was approximately half that of the froglets. When the nerve supply was augmented by deviating ipsilateral sciatic nerve bundles to the forelimb stump, almost all limbs, which were usually non-regenerative with normal innervation, regenerated heteromorphically. These results show that the decline in limb regenerative capacity during postmetamorphic growth is in part attributable to the reduction in innervation levels to below the threshold level required for regeneration. PMID- 1445788 TI - Study of yolk precursor transport in the avian ovary with the use of horseradish peroxidase. AB - Ovaries of adult Japanese quails were exposed in vivo to the exogenous protein horseradish peroxidase (HRP) for varying lengths of time to investigate ultrastructurally the permeability of the wall of these follicles, the protein uptake capacity of granulosa and oocyte and the kinetics of protein uptake in different stages. There is a sudden increase in permeability of the follicle wall from previtellogenesis to vitellogenesis. This is not due to a loss of sealing (tight) junctions in the granulosa cell layer, but is probably related to a permeability change in the basement membrane. The transition from the slow growth phase to the rapid growth during vitellogenesis is accompanied by a limited widening of the intercellular channels and the concomitant development of a complex endocytotic apparatus in the ooplasm. The slowing down of yolk deposition during the last day before ovulation is accompanied by a narrowing of the intercellular channel width. The granulosa cells show a high intracellular HRP uptake during intermediary yolk formation. Transcytosis through the granulosa cannot be excluded but is probably a minor pathway at certain stages. The light microscopically detectable uptake of HRP by the oocyte coincides with the start of exogenous vitellogenesis. After 90 sec of exposure to HRP (intravenous injection) the tracer can be found in the intercellular channels of the granulosa and in superficially located yolk spheres. On the other hand it takes 10 min for the tracer to traverse the cortex of the oocyte. PMID- 1445789 TI - N-glycosylated proteins interfere with the first cellular migrations in early chick embryo. AB - Cell adhesion and migration properties which are known to play a crucial role in developmental events seem to be modulated by variations in glycosylation of glycoproteins. In the chick embryo, the extracellular matrix (ECM) appears as a loose meshwork of fibrillar material in the space between the epiblast and the hypoblast shortly before the first major cell migrations start. Chick embryos treated with tunicamycin (TN), a specific inhibitor of N-linked glycosylation of proteins, show little or no ECM, diminished cell adhesion and a dramatic alteration in the architecture of the epiblast and of the hypoblast. The first major cell migrations which signal the onset of PS and gastrula formation are inhibited irreversibly in these embryos. Tunicamycin induces a substantial change in the labeling pattern with change in mobility of some polypeptides and with the induction or marked accentuation of multiple charged species (isoforms) of polypeptides different from these already present in the control blastoderm. The N-linked glycosylation of protein(s) that are synthesized during the interaction of the epiblast and of the hypoblast seem to play a critical role in cell adhesion and in the morphogenetic movements of gastrulation in the early chick embryo. PMID- 1445790 TI - Unilateral renal agenesis in chick embryos: a model for chronic renal insufficiency. AB - Although renal agenesis and dysgenesis are relatively common and significant birth defects, no animal model to date has been utilized to adequately study these developmental pathologies. Blockage of the migration of the mesonephric duct in Day 2 chick embryos results in unilateral renal agenesis (URA) on the operated side, thus providing a model of chronic renal insufficiency. Embryos with URA respond with an increase in the rate of growth of the remaining meso- and metanephric kidney. The allometric scaling of single (left) kidney weight to total body weight in control embryos is KM = 3.48M0.98 compared to KM = 3.02M1.16 in embryos with URA. In addition, embryos with URA exhibit a progressively polycystic mesonephros with distinct glomerulonephritis and expansion of the renal tubules. These renal changes are insufficient for normal urine (allantoic fluid) production and oliguria persists throughout incubation. While mortality is unaffected by URA in embryos up to Day 14 of incubation, there is a steady increase in mortality after Day 14; no chick embryo with URA lives beyond Day 18 of the 21-day incubation period. PMID- 1445791 TI - The human placenta becomes haemochorial at the 13th week of pregnancy. AB - Histological specimens of recent implantation sites are the basis of our current concept on human embryo implantation and placental development. In the Carnegie Collection maternal red blood cells were detected early in the primitive intervillous space (10th-12th day after conception). These cells were localized to the trophoblastic lacunae and originated from distended peripheral maternal sinusoids (Kaufmann, 1981). The classical theory states that progressively more and more maternal vessels are tapped. A true maternal blood flow is established around the 29th day. Dynamic investigations of human placental development in vivo are scarce and hampered by ethical considerations and the absolute requirement to refrain from using non aggressive and potentially harmful techniques. Despite these limitations such studies provide new insights that surprisingly contradict our previously and seemingly definitely established knowledge of the early phases of placental vascularization, and lead us to conclude that there is an absence of maternal blood circulation in the intervillous placental space (IVS) during the 12 first weeks of human pregnancy. PMID- 1445792 TI - Advances in the detection of ploidy differences in cancer by in situ hybridization. AB - Three main techniques allow the detection of changes in the cellular genomic content. The karyotyping procedure on metaphase spreads can give specific information on chromosome number and structural chromosome changes, but analyses are restricted to a limited number of chromosome spreads. Furthermore, cell culturing of (in particular solid) cancer specimens can result in selection of a minor tumour cell population with a high proliferative capacity. On the other hand, flow cytometry allows the analyses of large numbers of cells, but does not detect small variations in the DNA content or structural changes. The fluorescent in situ hybridization (FISH) procedure combines the advantages of the two former procedures, in that relatively large numbers of cells can be analysed easily and specific chromosomal changes can be detected. PMID- 1445793 TI - Identification and fate of a marker chromosome in methotrexate-resistant V79,B7 cells by flow karyotyping and sorting, metaphase analysis and in situ hybridization. AB - The chromosomes from a methotrexate (MTX)-resistant and its parental V79,B7 Chinese hamster cell line were analysed by the combined use of flow karyotyping and sorting, metaphase analysis and in situ hybridization with a probe for the dihydrofolate reductase (DHFR) gene responsible for methotrexate resistance. A marker chromosome with an elongated arm carrying the amplified DHFR gene was identified by in situ hybridization of metaphase cells of the methotrexate resistant line. In the flow karyotype the marker chromosome was found as an additional peak with a higher DNA content compared with the largest chromosome of the sensitive line. This was additionally verified by G-banding of the chromosomes sorted from the marker peak. Several other chromosomal rearrangements not associated with the amplified gene could be identified in the methotrexate resistant line by the combined use of flow karyotyping and metaphase analysis. The fate of the original marker chromosome was studied in cells growing several weeks in the absence of methotrexate, comparing flow karyotyping and metaphase analysis. The original marker chromosome was lost in about 50% of the cells after 5 weeks and in about 60% of the cells after 8 weeks; between 80 and 90% of the cells, however, contained marker chromosomes of various sizes. The MTX-resistance decreased in parallel during loss of the original marker chromosome. In conclusion, the study shows that the power of cytogenetic analysis is improved by the combined use of conventional cytogenetics, molecular cytogenetics and flow cytometry. PMID- 1445794 TI - Spontaneous regression of residual tumour burden: prediction by Monte Carlo simulation. AB - Current cancer treatment protocols are designed to release the tumour burden down to a small number of cells. In this study, we use Monte Carlo simulations to show that small populations of cells with intrinsic cell loss rates comparable to the cell loss rates observed clinically in human tumours, may regress spontaneously. Large populations of cells tend to grow under the same conditions of cell loss that result in extinction of small clones. Furthermore, minor variations in the intrinsic cell death probability near 0.50 result in large differences in the number of surviving cells calculated at the 100th generation. When Monte Carlo simulations of clonal growth resulted in clones with large populations (> 50 cells), the population as a whole behaved in a deterministic fashion (logarithmic growth) similar to those observed in clinically observed neoplasms and consistent with other published models of tumour growth. These findings provide a plausible explanation for the clinically observed failure of tumours to recur in instances where tumour burden remains following cancer therapy. The findings also demonstrate the usefulness of the Monte Carlo method to simulate biologic events in populations where the fate of each member of a population can be modeled probabilistically. PMID- 1445795 TI - S phase, an evolutionary chromatin condensation state from G1 to G2, in a breast epithelial cell line. AB - In order to better understand the changes in DNA organization during the cell cycle, we quantified the chromatin texture of breast epithelial cells and followed its evolution through a cell cycle. The diversity of quiescent cell states led us to limit this study to proliferating cell phases, and to choose a cell line with no G0 cells, the MDA AG cell line. We recently developed a methodology for characterizing in situ the cell cycle of breast epithelial cell lines using a cell image processor. This method is based on 15 densitometric and texture parameters computed on individual Feulgen-stained nuclei and on multiparametric analysis of the resulting data. Chromatin pattern assessment is based on nine texture parameters measured from grey-level co-occurrence and run length section matrices. In the present study, texture parameter computation showed gradual and progressive modifications of nuclear texture. While discrimination of G1, G2 and M phases was possible, we could not discriminate G1 from S and S from G2. The chromatin pattern (defined by these nine parameters) in the G1 and early S phases, on the one hand, and in the late S and G2 phases, on the other hand, were similar. The parameter values of cells in the S phase progressively increased from G1 to G2. Two interphase chromatin condensation states were distinguished in these breast cells: a base state characteristic of a prereplicative stage and a very granular state characteristic of a postreplicative stage. We hypothesized that S cells are a blend of these two states, the evolution of a non-duplicated state toward a duplicated one. PMID- 1445796 TI - Flow cytometric analysis of the cell cycle in chronic gastritis. AB - Flow cytometric cell cycle analysis was recorded in gastric biopsy specimens from patients with normal gastric mucosa (GM), superficial gastritis (SG) and chronic atrophic gastritis (CAG). Cell-cycle analysis showed significantly higher percentages of cells in S- and S+G2/M-phase in CAG than in SG and normal GM (P < 0.0001). Moreover, CAG with severe or moderate atrophy showed significantly higher percentages of cells in S-phase (P < 0.05) and S+G2/M-phase (P < 0.02) than CAG with mild atrophy in antrum. In fundus, even if this increase was observed, it did not reach statistical significance. Consideration of concomitant pathologic findings such as oesophagite, gastric or duodenal ulcer, duodenite or benign polyp allowed a better differentiation of CAG both in antrum and in fundus. Significantly higher S-phase was observed in CAG with severe or moderate atrophy than in CAG with mild atrophy (P < 0.05). No statistically significant results were observed in patients with normal gastric mucosa or chronic gastritis and a concomitant pathologic finding. PMID- 1445797 TI - Nuclear DNA ploidy in mammary carcinomas; using nuclear size as co-parameter reveals more complex patterns. AB - Static DNA measurements using nuclear size as a co-parameter have been made on cell populations from 106 consecutive patients with proper imprints from fresh tumour tissues or fine-needle aspirates. When DNA content is plotted against the nuclear size of each individual cancer cell in a scatter diagram, different patterns are found. These patterns indicate the presence of subpopulations, which may be overlooked using conventional flow cytometric analysis or other techniques relying only on the nuclear DNA content. The presence of these subpopulations might, in addition, interfere with a correct definition and estimation of the percentage of S-phase cells. PMID- 1445798 TI - Induction of AP-1 transcription factor components during T-cell activation by interleukin 1 and phorbol esters. AB - We have examined the effect of interleukin 1 (IL-1) and phorbol esters [12-O tetradecanoylphorbol-13-acetate (TPA)] on the expression of various components of the AP-1 transcription factor complex during T-cell activation. We previously found that a chloramphenicol acetyltransferase reporter gene driven by the collagenase TPA responsive element was expressed upon stimulation of T-cells by TPA and that this expression was enhanced when IL-1 was added as a costimulant; IL-1 alone had no effect on TPA responsive element-chloramphenicol acetyltransferase expression. In this study, we have found that stimulation of T cells by IL-1 and TPA is accompanied by activation of a subset of immediate early genes that comprise the AP-1 transcription factor complex. junB and fosB were rapidly induced following stimulation with TPA. Although the levels of other fos related mRNAs were also elevated, their maximal induction was delayed by approximately 5 h. IL-1 alone had little or no effect, but enhanced TPA induced transcription and steady-state levels of these mRNAs. The expression of fos and jun during T-cell activation was accompanied by increased specific binding of JunB, FosB, and fos-related antigen containing complexes to the TPA responsive element. These findings indicate that the synergistic effect of IL-1 and TPA on AP-1 mediated gene expression is due, in part, to the ability of IL-1 to enhance the expression of genes encoding specific AP-1 transcription factor components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445799 TI - Analysis of glutathione transferase P gene regulation with liver cells in primary culture. AB - Glutathione transferase P (GST-P) gene is specifically and highly activated during rat chemical hepatocarcinogenesis. We have previously cloned the GST-P gene and have identified putative regulatory regions. To further explore regulatory mechanisms, deletion constructs of the GST-P gene fused to the chloramphenicol acetyltransferase (CAT) structural gene were introduced into primary cultured rat hepatocytes by electroporation, and their activity was determined. The expression of the GST-P-CAT fusion gene is quite low in these cells as compared to that in both a rat fibroblast cell line, 3Y1 cells, and a rat hepatoma cell line, dRLh84. The presence of the strong enhancer GPEI did not elicit any enhancing activity at its original position, or when it was located 3' of the CAT gene, although this element does enhance CAT activity significantly when located adjacent to the promoter. Cotransfection of neither c-jun nor c-fos expression vector, nor both vectors, could enhance the CAT activity, even though GPEI consists of two phorbol ester response element-like sites. Furthermore, the expression of jun family gene was not correlated with GST-P gene expression either in primary cultured hepatocytes or in hepatoma cell lines. PMID- 1445800 TI - The ERGB/Fli-1 gene: isolation and characterization of a new member of the family of human ETS transcription factors. AB - All cellular ets proteins contain a region of high amino acid identity to those found in the last two exons of the ets-1 gene (C domain). We have identified and characterized a new member of the human ETS gene family, ERGB. The ERGB gene shows extensive amino acid identity to the human ERG and the mouse Fli-1 genes. The ERGB gene is found to be transcriptionally active in a variety of human cell lines and tissues, in contrast to the more restrictive expression pattern of the ERG gene. The ERGB gene encodes for a 3.2-kilobase mRNA containing an open reading frame of 451 amino acids. The ERGB gene, like human ETS1, is located on chromosome 11 and is transposed to chromosome 4 as a result of the translocation t(4;11) associated with leukemia. Pulse-field gel analysis suggests that ETS1 and ERGB are more than 200 kilobases apart. Similar to the other members of the ets family (ets 1, ets 2), this new member is also able to trans-activate transcription of a reporter gene linked to the ETS-binding sequences derived from either the GATA-1 promoter or an optimal Ets-binding site. PMID- 1445801 TI - Signal transduction defect appears to be the cause of rat prostate cancer cell fibroblast growth factor insensitivity. AB - Using monolayer cultures of clonally isolated C3 and T5 rat prostate cancer cells, we determined that acidic (aFGF) and basic (bFGF) fibroblast growth factors profoundly enhanced T5 cell thymidine incorporation with half-maximum stimulation at 0.53 and 0.35 ng/ml, respectively. In contrast, aFGF or bFGF enhancement of C3 cell thymidine incorporation was about 5% of that of T5 cells, and effects were principally mitogen concentration independent. Saturation analyses and cross-linking studies established that both C3 and T5 cells contained high-affinity FGF receptors of 120 and 145 kilodaltons and that receptor content and Kd of C3 and T5 cells were comparable. aFGF or bFGF stimulation of T5 cell thymidine incorporation profoundly decreased as cell plating density was reduced from 1.5 x 10(5) to 1.0 x 10(4) cells/well. The modest response of C3 cells to either aFGF or bFGF also decreased as cell plating density was reduced. Because heparin preserves FGF biological activity and enhances bFGF binding to high-affinity FGF receptors, we examined the effect of heparin on FGF stimulation of C3 cell thymidine incorporation. We found that changes in cell plating density and/or medium heparin concentration had variable, inconsistent effects. These were C3 cell plating density associated and included inhibition or modest enhancement of FGF effects. Binding analyses established that high-affinity bFGF binding of C3 and T5 cells immediately prior to assessing FGF-stimulated thymidine incorporation was comparable and independent of cell plating density, implying that C3 cell FGF insensitivity was not attributable to differences in C3 and T5 cell FGF receptor content at the time of mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445802 TI - Myb expression is higher in malignant human colonic carcinoma and premalignant adenomatous polyps than in normal mucosa. AB - Expression of the protooncogene c-Myb protein was assessed in normal mucosa and in tumor samples resected from six patients. We found that the tumor samples always expressed higher levels of full length Myb protein than the normal tissue. This contrasts with the situation in c-myb-associated hemopoietic malignancies of the mouse and chicken, in which Myb proteins are generally amino or carboxyl truncated. Tissues from five patients with colonic adenomatous polyps were also examined and found to express levels of Myb that were, in general, intermediate between those found in normal tissues and tumors. Of particular interest is that the more dysplastic polyps displayed higher Myb levels. In one patient with carcinoma and multiple colonic polyps, some polyps had intermediate levels of Myb, whereas one polyp with carcinoma in situ expressed tumor-like levels of Myb. To directly test the hypothesis that Myb expression may be important in determining the rate of colonic cell proliferation, we examined three colonic carcinoma cell lines and one polyp cell line. We found that the cell lines with the most rapid doubling times exhibited the highest Myb levels. In addition, we show that antisense myb oligonucleotides retard the proliferation of one of these colonic cell lines which expresses the highest level of Myb. PMID- 1445804 TI - Growth factors, receptor kinases, and protein tyrosine phosphatases in normal and malignant melanocytes. AB - Normal human melanocyte proliferation and differentiation is dependent on stimulation of one of three growth factor/receptor systems. They are fibroblast growth factor (FGF), hepatocyte growth factor (HGF), and mast cell growth factor (MGF), which activate the FGF receptor, c-Met, and c-Kit, respectively, known to be receptor tyrosine kinases. In contrast, human melanoma cells from primary nodular and metastatic lesions grow autonomously partially because of inappropriate production of basic FGF (bFGF) and continuous activation of the bFGF-receptor kinase. Activation of transmembrane receptor tyrosine kinases in melanocytes stimulates not only proliferation but also the expression of pigmentation. Melanoma cells constitutively express several tyrosyl phosphorylated proteins that in normal melanocytes are stimulated in response to growth factors. This high level of phosphorylation was not due to either the presence of constitutively active Kit kinase and Met kinase nor to the absence of any of several known protein tyrosine phosphatases. Because bFGF by itself does not transform melanocytes to melanomas, there must be additional cooperating factors that confer the malignant phenotype to pigment cells. PMID- 1445803 TI - Protein kinase C beta gene expression is associated with susceptibility of human promyelocytic leukemia cells to phorbol ester-induced differentiation. AB - To study the signal transduction pathway leading to phorbol 12-myristate 13 acetate (PMA)-induced differentiation in human promyelocytic HL-60 leukemia cells, we examined the expression of protein kinase C (PKC) isozyme genes in HL 60 cells that are susceptible or resistant to PMA-induced differentiation. The PKC-alpha, -beta, -gamma, -delta, epsilon, and -zeta transcript levels were assessed by Northern blotting, and the PKC-alpha, -beta, and -gamma protein levels were examined by immunoblotting. The PMA-resistant cell variants HL-525 and HL-534 were found to be deficient in the PKC-beta isozyme RNA and protein as compared with the PMA-susceptible HL-60 and HL-205 cell lines. In addition, a "delta-like" PKC RNA species identified in these cells demonstrated a reduced abundance in the HL-525 and HL-534 cells. Southern blot analysis indicated that the observed reduction in PKC-beta gene expression does not appear to be due to a gross deletion or rearrangement of the gene. The expression of the early response genes junB, c-fos, and c-jun was attenuated in PMA-treated HL-525 and HL-534 cells as compared to the PMA-treated HL-60 and HL-205 cells. These results suggest that the signal transduction pathway that leads to PMA-induced differentiation in the HL-60 cell system requires PKC-beta and/or delta-like PKC for the proper expression of the early response genes, and ultimately the expression of genes that define the mature state. PMID- 1445805 TI - Proinflammatory and antiinflammatory cytokines in multiple sclerosis and central nervous system acquired immunodeficiency syndrome. AB - While certain cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), IL-6, and transforming growth factor-beta (TGF-beta) may be involved in pro- and anti-inflammatory events in the central nervous system (CNS) of patients with multiple sclerosis (MS) and CNS acquired immunodeficiency syndrome (AIDS), there is not uniform consensus as to whether they are elevated or even detectable in all compartments of the body such as serum, cerebrospinal fluid (CSF), and tissue. Furthermore, if they are elevated in these diseases, there are no data as to whether they regulate the disease process itself. Myelin damage in MS is a punctate demyelination; in AIDS, it is a diffuse myelin pallor or dysmyelination. Oligodendrocytes are destroyed in MS but not CNS AIDS, suggesting a different mechanism for myelin loss in the two diseases. These different pathologies may provide clues about the role of macrophages, microglia, and/or the toxic products they produce in putatively giving rise to myelin damage. The stimuli that trigger such a destructive response by macrophages or glial cells and/or the regulation of the toxic events in the two diseases we would predict to be different. In MS, an effector cell-mediated lesion production and oligodendrocyte cell destruction seem to occur. We hypothesize that the effector is the inflammatory blood macrophage and/or microglial cell induced and promoted to its cytotoxic activity by a collaboration of neurotransmitters and cytokines. In CNS AIDS, virus-induced toxic products of glia and their diffusion through white and gray matter areas of the brain have been suggested. Such soluble mediators would then compromise metabolic processes of neurons and glia without widespread target cell loss. PMID- 1445806 TI - Interactions of cytokines with the hypothalamus-pituitary axis. AB - Major humoral mechanisms include the endocrine and immune systems, and there is substantial literature describing interactions between these systems during infection and inflammatory processes. Within the brain, such interactions are less well known. One major brain function altered during infection and inflammation and by several endocrine hormones is sleep. These changes in sleep provide a useful illustration of the interactions between cytokines and the hypothalamus-pituitary axis (HPA). Experimental evidence is reviewed that illustrates the interaction of cytokines, especially interleukin-1 (IL-1), with the HPA in regard to their effect on sleep. The evidence linking IL-1, growth hormone-releasing hormone/growth hormone, and corticotropin-releasing hormone to sleep regulation is reviewed. There is also evidence that shows that these two major sleep-regulatory systems are linked to each other. PMID- 1445807 TI - Natural regulators of T-cell lymphokine production in vivo. AB - The mammalian immune system possesses the intrinsic capacity to evoke a wide variety of functionally distinct effector mechanisms following stimulation by a particular antigenic substance. Such diversity in available responses is absolutely essential to the immunocompetent host, which must continually deal with a diverse set of potential pathogens within its ever-changing environment. The development of appropriate types of immune responses, therefore, represents a highly dynamic process that requires that an equivalent consideration be given to a large array of components, any one of which is capable of modulating the final outcome. While the nature and complexity of the antigen(s), plus the intracellular or extracellular mode of presentation, provide specificity and some selection to the developing process, the route of antigen entry, as well as the physiological status of the host at the time of antigen insult, also contribute significantly to the formation of any immune response. The overall objective of this article is to introduce the concept that platelet-derived growth factor (PDGF) (either preformed or synthesized in response to stimulation), plus a number of steroid hormones (some of which are end-organ metabolized at local tissue sites), can all play significant roles in the genesis of immunologic responses in vivo. PMID- 1445808 TI - Presentation of three different viral peptides is determined by common structural features of the human lymphocyte antigen-A2.1 molecule. AB - To assess whether similar or dissimilar molecular features of class I human lymphocyte antigen (HLA) molecules determine the presentation of structurally diverse peptides, we have examined the influence of different pockets within the HLA-A2.1 molecule on the presentation of three different viral peptides. The influenza virus M1 58-66, HTLV-I Tax peptide 12-19, and HCMV gB 619-628 are minimal peptides that induce HLA-A2.1-restricted non-cross-reactive CTL responses. The influence of distinct structural features of HLA-A2.1 on peptide presentation was analyzed using a panel of 14 HLA-A2 mutants each with single amino acid substitutions in one of six pockets that are located in the peptide binding site. Ten of the 14 mutants showed concordant effects on the presentation of all three peptides to their peptide-specific CTL lines. Four of the mutants had a negative effect on the presentation of only one or two of these viral peptides. These findings indicate that common structural features in HLA-A2 determine the binding and conformation of different peptides, and help to provide a plausible explanation for how diverse peptides bind to HLA-A2. PMID- 1445809 TI - Immunobiology of primary murine melanomas. AB - Primary cutaneous melanomas can be induced in inbred mice by applying a dose of dimethylbenz[a]anthracene to the skin of 4-day-old mice, and then applying repeated doses of a tumor promoter to the same site over a long period of time. Preliminary experiments suggest that the final incidence of melanomas is strongly influenced by the age at which the initiating dose of carcinogen is applied. Melanomas induced by this method in C3H mice are immunogenic and exhibit a high degree of cross-reactivity when tested by immunization and challenge in vivo. Exposing the mice to ultraviolet (UV) radiation during carcinogenesis dramatically accelerates the appearance of melanoma. We are attempting to determine how UV radiation potentiates melanoma induction by studying the growth of melanoma cells transplanted into UV-irradiated skin. Our studies suggest that UV irradiation accelerates the outgrowth of melanoma cells by means of a local, immunosuppressive effect on the skin. However, this effect is distinct from the ability of UV irradiation to alter epidermal Langerhans cells and interfere with the induction of contact hypersensitivity responses. We postulate that UV irradiation augments melanoma development by interfering with the efferent arm of the immune response in the UV-irradiated site. PMID- 1445810 TI - Tumor-specific antigens of mouse tumors. AB - This article reviews the serological analysis of cell surface antigens of chemically induced sarcomas of murine origin. This analysis, which was aimed at molecular characterization of the highly restricted tumor specific transplantation antigens of sarcomas, led to the initial biochemical identification and characterization of p53. The results of this early study clearly pointed to p53 as playing a key role in cellular proliferation and transformation. Current research of the tumor-specific or -associated antigens of chemically-induced sarcomas and melanomas of murine origin is also discussed. PMID- 1445811 TI - The use of congenitally immunodeficient mice to study human tumor metastases and immunotherapy. AB - Congenitally immunodeficient strains of mice have proven valuable in the development of relevant models to study human tumor biology, metastases, and immunotherapy. Local invasion and extensive multiorgan metastases in athymic mice have been obtained following orthotopic implantation or onplantation of histologically intact fragments of human tumors. In C.B-17 severe combined immunodeficient (SCID) mice or in triple immunodeficient, beige/nude/xid (BNX) mice, the development and spread of inoculated human leukemia/lymphoma and/or melanoma have mimicked, in some cases, those observed in patients. Reports of reconstitution of SCID and BNX mice with human myeloid or lymphoid cells have suggested that these models might be useful for the study of human immune responses to autologous tumors in vivo. The severe immunocompromised status of these mice have also led to evaluations of the therapeutic efficacy of adoptively transferred, tumor-reactive human T cells. In this report, we review the pertinent information currently available on the use of congenitally immunodeficient mice in studies of human cancer biology and treatment. PMID- 1445812 TI - In vitro growth patterns of normal human melanocytes and melanocytes from different stages of melanoma progression. AB - Based on the clinicopathological classification of distinct stages of tumor progression in the melanocytic system, we have investigated the in vitro growth patterns and requirements of normal melanocytes and melanocytes isolated from different lesions of melanoma progression. Normal melanocytes depend on a combination of insulin-like growth factor (IGF-I) or insulin, 12-O-tetradecanoyl phorbol-13-acetate (TPA), alpha-melanocyte stimulating hormone (alpha-MSH), and basic fibroblast growth factor (bFGF) for in vitro proliferation. Nevus cells display a reduced need for TPA and are largely independent of bFGF. Both melanocytes and nevus cells have a finite lifespan in vitro and show no spontaneous transformation, whereas melanoma cells can be grown indefinitely in vitro. Cells from primary melanomas require only IGF-I or insulin for continuous growth, and metastatic melanoma cells can proliferate in base medium without addition of any growth factors or proteins. This progressive growth autonomy is paralleled by an increased competence for endogenous growth factor production. Among these growth factors, bFGF and melanoma growth-stimulatory activity (MGSA) act in an autocrine fashion. Melanoma-derived growth factors without apparent autocrine function, such as platelet-derived growth factor A and B (PDGF-A and PDGF-B) and transforming growth factor-alpha (TGF-alpha), might still be important for melanoma growth by stimulating surrounding normal fibroblasts, endothelial cells, or keratinocytes to secrete growth-promoting factors. The significance of growth factors such as transforming growth factor-beta (TGF-beta) and melanoma-inhibiting activity II (MIA II), which have a potentially negative autocrine function, remains unknown. The successful propagation of melanocytic cells of all stages of melanoma progression has yielded valuable insight into the mechanisms of growth regulation and malignant transformation. PMID- 1445813 TI - Recognition of shared melanoma antigens by human tumor-infiltrating lymphocytes. AB - We have established that melanomas express shared tumor antigens (Ags) that can be recognized by T cells if presented in the context of self-MHC molecules. Tumor infiltrating lymphocytes (TILs) from six melanoma patients were tested for lysis of large panels of HLA-matched or unmatched targets representing a variety of tissue types. Lysis was specific for allogeneic melanomas sharing at least one HLA-A, -B, or -C Ag with TILs, and demonstrated commonly expressed tumor Ags. Similar findings were obtained when cytokine secretion by TILs was used to indicate specific Ag recognition. Transfection of the HLA-A2.1 gene into HLA-A2- melanoma lines conferred susceptibility to lysis by HLA-A2 restricted melanoma TILs, demonstrating expression of common tumor Ags among patients of diverse HLA types. These findings have important implications for developing broadly applicable cancer immunotherapies such as vaccines. PMID- 1445814 TI - The effect of environmental temperature and humidity on 24 h energy expenditure in men. AB - The effects of environmental temperature and humidity and their interaction on 24 h energy expenditure were measured using whole-body indirect calorimetry in eight normal-weight young men who wore standardized light clothing and followed a controlled activity regimen. A randomized-block experimental design was used, with temperature effects assessed by measurements at 20, 23, 26 and 30 degrees, while humidity was altered from ambient (50-65% relative humidity) to high (80 93% relative humidity) at 20 and 30 degrees only. There was no significant effect of humidity on 24 h energy expenditure at the two extreme temperatures in this range, though when periods of sleep and exercise were excluded the energy expenditure at high humidity was significantly higher than that ambient humidity (P < 0.02). The effect of temperature at ambient humidity levels showed lower values at 23 and 26 degrees than at 20 and 30 degrees (P < 0.02). The effect of temperature was not equally apparent in all components of the 24 h energy expenditure, as sleeping metabolic rate and the energy cost of walking and cycling showed no significant effect of temperature over this range. This raises the possibility that the effects of temperature are attributable to behavioural changes during the waking portion of the day rather than any non-shivering thermogenic mechanisms at tissue level. PMID- 1445815 TI - Compensatory growth in broiler chicks fed on Lemna gibba. AB - The growth of broiler chickens on diets containing various levels of Lemna gibba was evaluated. Groups of broiler chicks were fed on diets containing 0-400 g Lemna gibba/kg for 3 weeks. These chickens were then changed to standard diets for a further 2 weeks. As the level of Lemna gibba increased, feed consumption and weight gain decreased. However, when diets were changed to the standard diet, compensatory growth was observed. In a second experiment, diets were formulated with a metabolizable energy of 5.02 MJ (1200 kcal)/kg Lemna gibba and included a finer-milled Lemna gibba. Chickens were fed on diets containing 0-300 g Lemna gibba/kg for 4 weeks. Each group was then divided into two subgroups. For the next 2 weeks one of these sub-groups was maintained on the experimental (Lemna gibba) diets (LL), while the other sub-group was changed to a standard diet (LS). Bird fed at levels above 150 g Lemna gibba/kg had decreased consumption and weight gain. These birds when changed to a standard diet tended to have increased weight gain compared with chickens continuously fed standard rations. LS birds had significantly higher weight gains and feed consumption and lower feed conversion than LL birds. In contrast to older birds, chicks fed on Lemna gibba at high concentrations showed growth retardation. When changed back to a standard diet they demonstrated normal or compensatory growth. PMID- 1445816 TI - Effects of repeated gestation and lactation on milk n-6 fatty acid composition in rats fed on a diet rich in 18:2n-6 or 18:3n-6. AB - The present study examined the effect of repeated gestation and lactation on the levels of long-chain n-6 polyunsaturated fatty acids in rat milk fat, and examined whether such levels might be modulated by supplementing the diet of the lactating dams with either (g/kg) 50 safflower oil (SFO; containing 800 g 18:2n 6/kg), or 50 evening primrose oil (EPO; containing 720 g 18:2n-6 and 90 g 18:3n 6/kg). The milk was collected at three different times (days 1, 8 and 15) in each given lactation period from female Sprague-Dawley rats which were successively bred for four pregnancies and lactations. Results showed that dietary fat and breeding frequency had no significant effects on milk triacylglycerol content, but they modified the pattern of milk fatty acids in both triacylglycerol and phospholipid fractions. After three or four successive breedings rats fed on EPO produced milk containing less saturated but more monounsaturated and polyunsaturated fatty acids compared with those fed on SFO. During the course of lactation the levels of n-6 metabolites, e.g. 18:3n-6, 20:3n-6 and 20:4n-6, in milk fat declined progressively. However, they were consistently higher in the EPO group than in the SFO group. These findings suggest that the levels of long chain n-6 metabolites in the milk fat may be increased through supplementing the maternal diet with 18:3n-6. PMID- 1445817 TI - The intake, digestion and protein degradation of grazed herbage by early-weaned lambs. AB - Sixty-four intact lambs and twenty-four lambs fitted with a duodenal cannula were weaned at 6 weeks of age and grazed pure species swards of either lucerne (Medicago sativa), white clover ((Trifolium repens), ryegrass (Lolium perenne) or prairie grass (Bromus catharticus) for 6 weeks. Intake and duodenal digesta flow were estimated when lambs were 8 and 12 weeks of age. Lambs grazing the two legume species grew at a similar rate, as did lambs grazing the two grass species. Legumes promoted a 38% higher growth rate than grasses. The higher growth rate of lambs grazing legumes was associated with a 36% higher digestible organic matter intake (DOMI; 29.5 and 21.7 g/kg body-weight per d for legume and grass respectively) and a 33% higher duodenal non-ammonia-nitrogen (NAN) flow (1.22 and 0.92 g/kg body-weight per d respectively). There was no species difference in the site of organic matter digestion; on average 0.56 of DOMI was apparently digested in the rumen and 0.77 of DOMI was truly digested in the rumen. There was no difference in duodenal NAN flow, relative to DOMI (average, 43 g/kg) or to organic matter apparently digested in the rumen (80 g/kg). Similarly, there was no difference in microbial N flow relative to duodenal NAN (0.50 g/g) and organic matter apparently (41 g/kg) or truly (29 g/kg) digested in the rumen. It was concluded that the higher growth rates achieved by lambs grazing legumes were due to higher intakes which increased the total quantity of nutrients supplied despite more protein being lost in the rumen of lambs consuming legumes. PMID- 1445818 TI - Acetylation of peptides inhibits their degradation by rumen micro-organisms. AB - Proteins and peptides were acetylated using acetic anhydride in order to block their N-terminal amino groups and thereby to prevent their hydrolysis by rumen microbial aminopeptidases. The effects of acetylation on peptide breakdown and ammonia production were determined by incubating unmodified and acetylated substrates with sheep rumen micro-organisms in vitro. Ammonia production from casein and lactalbumin was affected little by acetylation, but acetylation of the corresponding enzymic hydrolysates caused ammonia production to be more than halved after 3-6 h incubation. Estimation of peptides remaining in rumen fluid showed that the decreased ammonia production was a consequence of peptides being hydrolysed more slowly. Acetylated Ala-Ala, Ala-Ala-Ala (Ala3), Leu-Gly-Gly, Phe Gly-Gly and Val-Gly-Ser-Glu survived incubation with rumen fluid in vitro for 6 h, whereas almost none of the corresponding unmodified peptides was present at 6 h. The protection afforded to larger pure peptides was less reliable: for example, 72% of acetylated bradykinin was hydrolysed after 1 h. N-Acetyl Ala3 had only a minor inhibitory effect on the breakdown of Ala3 and Ala4, suggesting that although acetyl peptides were broken down more slowly than unmodified peptides they did not inhibit peptidase activity. PMID- 1445819 TI - Responses in tissue protein synthesis to sub- and supra-maintenance intake in young growing sheep: comparison of large-dose and continuous-infusion techniques. AB - In ten lambs (average live weight 33 kg), five offered 300 g/d (approximately 0.6 x maintenance; L) and five 900 g/d (1.8 x maintenance; H), tissue protein synthesis was measured by three procedures simultaneously. The techniques involved continuous infusion of [U-14C]phenylalanine and [1-13C]leucine over 7-8 h followed by a terminal large dose of [15N]phenylalanine during the last 30 or 60 min. Rates of protein synthesis were then calculated based on the free amino acid or oxo-acid isotopic activity in either arterial, iliac venous blood or tissue homogenate for the continuous-infusion studies, or on plasma or tissue homogenate for the large-dose procedure. For muscle (> 99%), and to a lesser extent skin (85-93%), effective flood conditions were achieved with the [15N]phenylalanine but were either not established or maintained for liver and tissues of the gastrointestinal tract (< 50%). The large dose of phenylalanine also caused changes in the concentration and isotopic activity of blood leucine and 4-methyl-2-oxo-pentanoate. Based on the assumption that the large-dose procedure yields the closest value for the true rate of protein synthesis (L 1.97%/d, H 2.85%/d) then, for muscle, only values based on the homogenate as precursor gave comparable results for both leucine (L 1.83%/d, H 3.01%/d) and phenylalanine (L 1.67%/d, H 2.71%/d) continuous infusion. The values based on the arterial or venous amino or oxo-acid were significantly less, more so at the lower intake. In contrast, for skin, a tissue dominated by export protein synthesis, values from the large-dose procedure (L 6.37%/d, H 10.98%/d) were similar to those derived with arterial or venous metabolites as precursor (L 5.23 and 6.93%/d, H 9.98 and 11.71%/d for leucine), but much less than those based on homogenate data. Based on the large-dose technique, protein synthesis increased with intake in muscle (P < 0.001), skin (P = 0.009) and liver (26.7 v. 30.5%/d; P = 0.029). The contributions of muscle and skin to total protein synthesis were approximately equal. The incremental efficiency of conversion for muscle of synthesized protein into deposition appeared to be similar to values reported for rodents. PMID- 1445820 TI - Effect of food intake on hind-limb and whole-body protein metabolism in young growing sheep: chronic studies based on arterio-venous techniques. AB - Whole-body protein synthesis, estimated by the irreversible loss rate procedure, and hind-leg protein metabolism determined by arterio-venous techniques were monitored in response to three nutritional conditions (approximately 0.6, 1.2 and 1.8 x energy maintenance (M)) in ten wether lambs (33 kg average live weight). In all lambs and treatments measurements were based on radiolabelled phenylalanine, but the terminal procedures (five at 0.6 x M and five at 1.8 x M) also included infusion of [1-13C]leucine; this permitted comparison of amino acids catabolized (leucine) and non-metabolized (phenylalanine) by the hind-limb tissues. Whole body protein synthesis increased with intake and the relationship with energy expenditure was slightly lower than that reported previously for pigs and cattle. The efficiency of protein retention:protein synthesis did not exceed 0.25 between the two intake extremes. Effects of intake on amino acid oxidation were similar to those observed for cattle. Hind-limb protein synthesis also increased significantly (P < 0.001) in response to intake. Estimates of protein gain, from net uptake values, indicated that the tissues made a greater proportional contribution to total protein retention above M and to protein loss below M, emphasizing the role played by muscle tissue in providing mobile protein stores. The rates of protein synthesis calculated depended on the selection of precursor (blood) metabolite, but rates based on leucine always exceeded those based on phenylalanine when precursor from the same pool was selected. The incremental efficiency of protein retained:protein synthesis was apparently unity between 0.6 and 1.2 x M but 0.3 from 1.2 to 1.8 x M. Blood flow through the iliac artery was also proportional to intake. Leucine and oxo-acid catabolism to carbon dioxide increased with intake such that the metabolic fate of the amino acid was distributed in the proportion 2:1 between protein gain and oxidation. The rates of oxidation were only 1-3% the reported capacity of the rate-limiting dehydrogenase enzyme in muscle, but sufficient enzyme activity resides in the hind-limb adipose tissue to account for such catabolism. PMID- 1445821 TI - Impairment of cysteine synthesis from methionine in rats exposed to surgical stress. AB - The activity of liver cystathionase (EC 4.4.1.1) was decreased after 3 d of stress induced by surgery. The rate of L-cysteine synthesis from L-methionine was significantly higher in isolated hepatocytes from controls than in hepatocytes from rats suffering from surgical stress. The half-life of L-[2(n)-3H]methionine was significantly higher in rats submitted to surgical stress than in controls. Plasma L-methionine:L-cystine ratio was higher in stressed rats than in controls. L-cystine uptake was significantly increased in the surgically-stressed rats when compared with the controls. All these facts are consistent with the hypothesis that the observed inhibition of cystathionase is physiologically important and that L-cysteine might be considered as an essential amino acid in cases of surgical stress. PMID- 1445822 TI - The cholesterol-raising effect of coffee in the Syrian hamster. AB - Adult male Syrian hamsters were fed on a high-fat diet with or without access to boiled coffee. Plasma total, low-density-lipoprotein- and high-density lipoprotein-cholesterol and triacylglycerol concentrations were increased by the coffee and very-low-density-lipoprotein-cholesterol concentrations were lowered. It is concluded that the Syrian hamster is a suitable animal model in which to study the hypercholesterolaemic effect of coffee. PMID- 1445823 TI - Lipid composition and fluidity of the erythrocyte membrane in copper-deficient rats. AB - The influence of dietary copper on lipid composition, phospholipid fatty acid and protein profiles and fluidity of the erythrocyte membranes of rats is reported. In general Cu deficiency in rats induced some changes in the phospholipid-fatty acid profile of erythrocyte membranes when compared with Cu-adequate animals. Stearic (18:0) and docosadienoic (22:2n-3) acids contents, for example, were significantly increased (P < 0.001) while oleic (18:1n-9) and linolenic (18:3n-3) acid contents were significantly depressed (P < 0.001) as a result of Cu deficiency. Moreover the cholesterol:phospholipids molar ratio and the cholesterol (mol):membrane proteins (mg) ratio in Cu-deficient rats were, to different degrees, significantly lower than in animals fed on Cu-adequate diets. In addition, diets deficient in Cu led to a reduction in erythrocyte membrane fluidity (P < 0.001) as assessed by the intramolecular excimer fluorescence of 1,3-di(1-pyrenyl) propane. However, no significant alteration in the phospholipid:protein ratio was observed as a result of differences in dietary treatment. The pattern of erythrocyte membrane proteins obtained with sodium dodecyl sulphate-polyacrylamide gel electrophoresis did not seem to be influenced by Cu-deficient diets. PMID- 1445824 TI - Glycaemic index of conventional carbohydrate meals. AB - The glycaemic index (GI) and the triacylglycerol response were measured in thirty non-insulin-dependent diabetes mellitus patients given 50 g portions of five different conventional Indian meals containing semolina (Triticum aestivum) cooked by two different methods, or combinations of semolina and pulse (black gram dhal (Phaseolus mungo), green gram dhal (Phaseolus aureus) or Bengal gram dhal (Cicer arietum)). There were no significant differences among meals in mean GI except for meals based on roasted semolina or semolina-black gram dhal. Compared with the blood glucose response for a 50 g glucose load, only meals based on steam-cooked semolina and semolina-Bengal gram dhal elicited a significantly lower response at 1 h postprandially, and only meals based on semolina-black gram dhal at 2 h postprandially. No significant differences were found among the meals in the triacylglycerol-response. PMID- 1445825 TI - The effects of feed intake and purified cellulose on the endogenous ileal amino acid flow in growing pigs. AB - The effects of level of feed intake (0.8, 1.2 and 1.6 kg/d) and body-weight of the pig (49 and 92 kg) in Expt 1, and dietary neutral-detergent fibre (NDF; 30, 60, 90, 120 and 150 g/kg) in Expt 2 on the endogenous ileal flow of amino acids (AA) and nitrogen were studied with protein-free diets into which purified wood cellulose was incorporated at the expense of maize starch. In Expt 1, one of the protein-free diets containing 90 g NDF/kg was used. Female pigs were fitted with a simple 'T' cannula at the terminal ileum. In Expt 1, the endogenous ileal AA and N flow, expressed as g/kg dry matter (DM) intake, decreased significantly (P < 0.05) with increasing DM intake, except for proline. By contrast, the values expressed as g/d remained constant. There was no significant difference in endogenous ileal flow (P > 0.05) between initial body-weights of 45 and 90 kg except for histidine, isoleucine, phenylalanine, threonine, valine and serine, in which the ileal flow determined at the higher body-weight was significantly higher (P < 0.05). In Expt 2, the effects of dietary cellulose levels on the endogenous ileal flow of AA and N were not significant (P > 0.05), although the values tended to increase as dietary cellulose levels increased for most AA and for N. It is concluded that the daily endogenous ileal flow of AA and N remains relatively similar at different DM intake and cellulose levels. Therefore, correction of apparent ileal digestibility of AA and N to the true ileal digestibility should be made with the endogenous ileal flow values expressed on a daily amount basis, not the values expressed on a DM intake basis. PMID- 1445826 TI - The effects of ispaghula on rat caecal fermentation and stool output. AB - The colonic fermentation of ispaghula, a mucilage from Plantago ovata composed mainly of arabinoxylans, and its effects on stool output and caecal metabolism were investigated. Four groups of eight rats were fed on a basal diet (45 g non starch polysaccharides/kg) for 28 d. The diet was then supplemented with ispaghula (g/kg; 0, 5, 15 or 50) for 28 d. Ispaghula increased stool dry weight and apparent wet weight but faecal water-holding capacity (amount of water held per g dry faecal material at 0.2 mPa) was unchanged. The extent of faecal drying in the metabolism cages was measured for rats fed on the basal diet and 50 g ispaghula/kg diet. At the faecal output levels encountered, only an 8% loss of wet weight would be predicted over 24 h and this was independent of diet. Faecal short-chain fatty acid (SCFA) concentration did not change but SCFA output increased. The molar proportion of SCFA as propionic acid increased and faecal pH was reduced. Values from pooled faecal samples suggested that approximately 50% of the ingested ispaghula was excreted by the 50 g ispaghula/kg diet group. Diaminopimelic acid (a constituent of bacterial cells) concentrations fell but output was unchanged indicating no change in bacterial mass. Similar changes were seen in the caecal contents but caecal pH and SCFA were unaffected. Ispaghula increased both caecal and colonic tissue wet weight and colonic length. Our results suggest that ispaghula is partly fermented in the rat caecum and colon, and loses its water-holding capacity. However, it is still an effective stool bulker and acts mainly by increasing faecal water by some unknown mechanism. PMID- 1445827 TI - Comparison of the effects of cassava (Manihot esculenta Crantz) organic cyanide and inorganic cyanide on muscle and bone development in a Nigerian breed of dog. AB - Effects of cassava (Manihot esculenta Crantz)-borne organic cyanide and inorganic cyanide in the form of sodium cyanide on bone and muscle development were investigated in eighteen dogs of Nigerian breed. After 16 weeks of stabilization in the laboratory from the time of purchase when the dogs were fed on the same diet, they were randomly assigned to three experimental groups of six dogs each. The control group was fed on rice while the other two groups were fed on either cassava (gari) or rice plus cyanide. The three diets were made isoenergetic and isonitrogenous by varying the quantity of meat incorporated into them. The results obtained after 14 weeks of feeding the respective diets indicated that there was retardation of muscle development in the gari-fed dogs. This may have resulted from gluconeogenesis from muscle protein associated with suppression of production of insulin by the pancreas in this group. The results indicated also that the effects of inorganic dietary cyanides on muscle development were different. Both forms of dietary cyanides, however, had no adverse effect on bone development. PMID- 1445828 TI - Nutritional outcome and immunocompetence in mice fed on a diet containing raw field beans (Vicia faba, var. minor) as the source of protein. AB - Feeding growth mice on diets containing raw field beans (Vicia faba var. minor) as the only source of protein brought about an impairment in growth, muscle mass and liver weight. No changes in food consumption were observed, but the food intake:weight gain ratio was increased in those animals. Plasma protein, triacylglycerols and cholesterol values were not affected by the dietary treatment although serum glucose and zinc levels fell after legume intake as well as the number of circulating erythrocytes. The relative enlargement of thymus and spleen in the legume-fed mice was apparently accompanied by a reduction in the cell number and an increase in cell size, while the protein synthesis capacity followed differentiated patterns in both tissues when assessed through protein, DNA and RNA determinations. The haemagglutination titres and the number of rosette-forming cells were lower in those animals fed on the field bean diet as well as the splenic lymphocyte responses to phytohaemagglutinin, Concanavalin A or lipopolysaccharide mitogens used to evaluate the functional status of T and B lymphocytes. The present study describes, apparently for the first time in mice, the involvement of field bean intake in some immunological disturbances affecting both humoral- and cell-mediated aspects of the immune response. PMID- 1445829 TI - Influence of low dietary lipid content on anorexia and [14C]glucose uptake in the intestine of zinc-deficient mice. AB - Zinc deficiency was induced in adult male mice by feeding them for 8 weeks on a purified semi-synthetic Zn-deficient diet (ZD) containing 90 g lipid/kg (60 g maize oil plus 30 g cod-liver oil). One group was then fed on a low-lipid Zn deficient diet (ZDLR) containing 30 g cod-liver oil/kg as the sole lipid source for a further 8 weeks. At the end of the experiment the stomach clearance rate, daily food intake, body-weight gain and [14C]glucose uptake in the intestine were significantly higher in group ZDLR than in mice that continued eating the Zn deficient lipid-adequate diet ZD, and were comparable to results for a group given a Zn-supplemented diet. These results suggest that the pathogenesis of anorexia, nutrient malabsorption and growth retardation are secondary to lipid malabsorption resulting from Zn deficiency. PMID- 1445830 TI - Erythrocytes, erythrocyte membranes, neutrophils and platelets as biopsy materials for the assessment of zinc status in humans. AB - During a controlled zinc depletion-repletion study, fifteen men aged 25.3 (SD 3.3) years were fed on a low-Zn diet with high phytate:Zn and phytate x calcium:Zn molar ratios for 7 weeks, followed by a 2 week repletion period when 30 mg supplemental Zn/d was given. Changes in plasma, urine, and hair Zn concentrations, taste acuity, and cellular immune response confirmed the development of mild Zn deficiency. Zn concentrations in neutrophils, platelets, erythrocytes and erythrocyte membranes, mean platelet volume, and activities of alkaline phosphatase (EC 3.1.3.1) and alpha-D-mannosidase (EC 3.2.1.24) in neutrophils did not respond to changes in Zn status. In contrast, alkaline phosphatase activity in erythrocyte membranes showed a significant decline which was consistent in all subjects (nmol product formed/min per mg protein; baseline v. 7-week Zn depletion, 0.656 (SD 0.279) v. 0.506 (SD 0.230), at 7 weeks; P < 0.05); neutral phosphatase activity remained unchanged. Alkaline phosphatase activity in erythrocyte membranes may be a potential index of Zn status in humans. PMID- 1445831 TI - Efficacy of massive oral doses of retinyl palmitate and mango (Mangifera indica L.) consumption to correct an existing vitamin A deficiency in Senegalese children. AB - Administration of large oral doses of retinyl palmitate has become the most widely practised vitamin A deficiency prevention strategy in developing countries. We conducted a follow-up study among 220 Senegalese children aged 2-7 years suffering from moderate undernutrition to determine the efficacy of vitamin A treatment on their vitamin A status assessed by biochemical and cytological (impression cytology with transfer) methods. The first examination (T = 0 m[onth]) was carried out during April 1989, before the mango (Mangifera indica L,) harvest. The second examination (T = 2 m) was carried out 2 months after vitamin A treatment during June 1989 when ripe mangoes become widely available. Conjunctival cells of the eyes of the children with or without ocular inflammation were responsive to vitamin A administration (P < 0.01). There was a significant increase (P < 0.001) in mean serum retinol and beta-carotene levels between T = 0 m and T = 2 m. Mean serum retinol-binding protein (RBP) and transthyretin (TTR) levels did not differ significantly (P > 0.05) at T = 0 m and T = 2 m. Despite the intake of vitamin A, 54% of the children who had abnormal cytology at T = 0 m remained abnormal at T = 2 m. This was due to inadequate levels of TTR and RBP, presumably due to the cereal diet eaten by the Senegalese population. children with abnormal eye cytology had lower serum retinol levels than those with normal eyes at T = 0 m, and beta-carotene values did not correlate with eye cytological abnormalities at T = 0 m. Children with normal cytology had higher serum retinol and also beta-carotene levels than those with abnormal cytology after massive oral doses of vitamin A and consumption of mangoes at T = 2 m. Retinyl palmitate may, therefore, only lead to partial cytological improvement due to a lack of retinol-carrier proteins but dietary beta-carotene may also be involved. PMID- 1445832 TI - Importance of specific adenosine N7-nitrogens for efficient cleavage by a hammerhead ribozyme. A model for magnesium binding. AB - Five modified hammerhead ribozyme/substrate complexes have been prepared in which individual adenosine N7-nitrogens have been excised. The modified complexes were chemically synthesized with the substitution of a single 7-deazaadenosine (c7A) base analogue for residues A11, A14, A26, A27, or A28. Two of the base analogues, c7A11 and c7A14, occur in a 19-mer ribozyme, while the remaining three residues, c7A26, c7A27, and c7A28, are present in a 24-mer substrate. Under stoichiometric conditions, four of the complexes are cleaved with relatively little change in rate when compared with that of the native complex. However, the relative rate for the c7A11 complex is some 35-fold slower than that of the native complex. Steady-state kinetic analyses indicate that the cleavage efficiencies, as measured by kcat/KM, for the c7A14, c7A26, c7A27, and c7A28 complexes are reduced 18-fold, 10-fold, 34-fold, and 16-fold, respectively. These reductions in cleavage efficiency are primarily a result of lower kcat values. By comparison, the cleavage efficiency of the c7A11 complex is reduced more than 200-fold relative to that of the native complex, again primarily as a result of a lower kcat value. The results suggest that the N7-nitrogen of A11 in the hammerhead ribozyme/substrate complex is critical for efficient cleavage activity. The results of the present work, in combination with those from previous reports, indicate that five critical functional groups are located within the tetrameric sequence G10A11U12G13. A preliminary model for the binding of a single magnesium cofactor to this portion of the sequence is proposed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445833 TI - PKC epsilon is involved in granulocyte-macrophage colony-stimulating factor signal transduction: evidence from microphysiometry and antisense oligonucleotide experiments. AB - We have used microphysiometry and antisense methodology to show that the epsilon isoenzyme of protein kinase C (PKC) is involved in the signal transduction pathway of granulocyte-macrophage colony-stimulating factor (GM-CSF) in a human bone marrow cell line, TF-1. These cells require GM-CSF or a related cytokine for proliferation. When the cells are appropriately exposed to GM-CSF, they exhibit a burst of metabolic activity that can be detected on the time scale of minutes in the microphysiometer, a biosensor-based instrument that measures the rate at which cells excrete protons. These cells express PKC alpha and -epsilon, as determined by Western blot analysis. Treatment with isoenzyme-specific antisense oligonucleotides inhibits expression appropriately, but only inhibition of PKC epsilon appreciably diminishes the burst of metabolic activity induced by GM-CSF. Consistent with the involvement of PKC epsilon, GM-CSF appears to activate phospholipase D and does not cause a detectable increase in cytosolic [Ca2+]. PMID- 1445834 TI - A repair system for 8-oxo-7,8-dihydrodeoxyguanine. AB - Active oxygen species can damage DNA and may play a role in aging and carcinogenesis. We have tested MutY glycosylase for activity on undamaged mispairs as well as mispairs formed with the oxidatively damaged substrates, 8 oxo-7,8-dihydrodeoxyguanine (GO) or 8-oxo-7,8-dihydrodeoxyadenine (AO). MutY acts as a glycosylase on four of the heteroduplexes tested, A/G, A/GO, A/C, and A/AO, removing the undamaged adenine from each substrate. Genetic data suggest that the primary substrate for MutY glycosylase in vivo is the A/GO mispair. We present biochemical evidence demonstrating that MutY glycosylase is an important part of a repair system that includes the MutM and MutT proteins. The GO repair system is dedicated to the repair of the oxidatively damaged guanine and the mutations it can induce. PMID- 1445835 TI - Evidence that a minor groove-binding peptide and a major groove-binding protein can simultaneously occupy a common site on DNA. AB - Affinity cleaving proteins have been synthesized based on the DNA-binding domain of the yeast transcriptional activator GCN4 with the DNA cleaving moiety Fe.EDTA attached at the NH2 terminus [Oakley, M. G., & Dervan, P. B. (1990) Science 248, 847]. Cleavage patterns generated by Fe-EDTA-GCN4(226-281) bound to the DNA sites 5'-CTGACTAAT-3' and 5'-ATGACTCTT-3' reveal that the NH2 termini of the GCN4 DNA binding domain are located in the major groove of DNA, 9-10 base pairs apart, consistent with a Y-shaped dimeric structure. 1-Methylimidazole-2-carboxamide netropsin (2-ImN) is a designed synthetic peptide which binds in the minor groove of DNA at 5'-TGACT-3' sites as an antiparallel, side-by-side dimer [Mrksich, M., Wade, W. S., Dwyer, T. J., Geierstanger, B. H., Wemmer, D.E., & Dervan, P. B. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 7586]. Through the use of Fe.EDTA GCN4(226-281) as a sequence-specific footprinting agent, it is shown that the dimeric protein GCN4-(226-281) and the dimeric peptide 2-ImN can simultaneously occupy their common binding site in the major and minor grooves of DNA, respectively. The association constants for 2-ImN in the presence and in the absence of Fe.EDTA-GCN4(226-281) are found to be similar, suggesting that the binding of the two dimers is not cooperative. PMID- 1445836 TI - Photoreactions of thymine and thymidine with N-acetyltyrosine. AB - We report here the photoinduced formation of a thymine-N-acetyltyrosine adduct. Irradiation of dilute solutions of thymine in the presence of N-acetyltyrosine (NAT) leads to the formation of N-acetyl-4-hydroxy-3-(6-hydrothymin-5 yl)phenylalanine (I), isolated as a mixture of the 5R and 5S diastereoisomers; the photoreaction occurs when irradiation is done either at lambda = 254 nm or at wavelengths of lambda > 290 nm. Irradiation of thymidine in the presence of NAT and of thymine in the presence of tyrosine leads to analogous photoadducts. The photoreaction of thymine with NAT is completely quenched by oxygen and cannot be sensitized by acetone. The likely mechanism involves initial photoionization of the amino acid and deprotonation to form the phenoxyl radical. Thymine then probably captures the released aqueous electron, leading to protonation at C6 of the resulting radical anion. Combination of the phenoxyl and 5,6-dihydrothymin-5 yl radicals would then lead to formation of the final products. The quantum yield for production of the thymine-NAT adduct at pH 7.8 was estimated to be about 5.5 x 10(-4), while a value of 2.3 x 10(-3) was estimated for production of corresponding thymidine adduct at pH 8.1. The dependence of the quantum yield for adduct formation on pH has been determined for both the thymine and thymidine reactions with NAT; the maxima in the quantum yield profiles occur at pH 8-8.5, while appreciable values were measured at pH 7.5. We have also demonstrated that a similar reaction occurs when tyrosine is located within a peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445837 TI - Influence of pH on the equilibrium association constants for oligodeoxyribonucleotide-directed triple helix formation at single DNA sites. AB - The energetics of oligodeoxyribonucleotide-directed triple helix formation for the pyrimidine.purine.pyrimidine structural motif were determined over the pH range 5.8-7.6 at 22 degrees C (100 mM Na+ and 1 mM spermine) using quantitative affinity cleavage titration. The equilibrium binding constants for 5' TTTTTCTCTCTCTCT-3' (1) and 5'-TTTTTm5CTm5CTm5CTm5CTm5CT-3' (2, m5C is 2'-deoxy-5 methylcytidine) increased by 10- and 20-fold, respectively, from pH 7.6 to 5.8, indicating that the corresponding triple-helical complexes are stabilized by 1.4 and 1.7 kcal.mol-1, respectively, at the lower pH. Replacement of the five cytosine residues in 1 with 5-methylcytosine residues to yield 2 affords a stabilization of the triple helix by 0.1-0.4 kcal.mol-1 over the pH range 5.8 7.6. An analysis of these data in terms of a quantitative model for a general pH dependent equilibrium transition revealed that pyrimidine oligonucleotides with cytidine and 5-methylcytidine form local triple-helical structures with apparent pKa's of 5.5 (C+GC triplets) and 5.7 (m5C+GC triplets), respectively, and that the oligonucleotides should bind to single sites on large DNA with apparent affinity constants of approximately 10(6) M-1 even above neutral pH. PMID- 1445838 TI - A magnesium-induced conformational transition in the loop of a DNA analog of the yeast tRNA(Phe) anticodon is dependent on RNA-like modifications of the bases of the stem. AB - Two single-stranded DNA heptadecamers corresponding to the yeast tRNA(Phe) anticodon stem-loop were synthesized, and the solution structures of the oligonucleotides, d(CCAGACTGAAGATCTGG) and d(CCAGACTGAAGAU-m5C-UGG), were investigated using spectroscopic methods. The second, or modified, base sequence differs from that of DNA by RNA-like modifications at three positions; dT residues were replaced at positions 13 and 15 with dU, and the dC at position 14 with d(m5C), corresponding to positions where these nucleosides occur in tRNA(Phe). Both oligonucleotides form intramolecular structures at pH 7 in the absence of Mg2+ and undergo monophasic thermal denaturation transitions (Tm = 47 degrees C). However, in the presence of 10 mM Mg2+, the modified DNa adopted a structure that exhibited a biphasic "melting" transition (Tm values of 23 and 52 degrees C) whereas the unmodified DNA structure exhibited a monophasic denaturation (Tm = 52 degrees C). The low-temperature, Mg(2+)-dependent structural transition of the modified DNA was also detected using circular dichroism (CD) spectroscopy. No such transition was exhibited by the unmodified DNA. This transition, unique to the modified DNA, was dependent on divalent cations and occurred most efficiently with Mg2+; however, Ca2+ also stabilized the alternative conformation at low temperature. NMR studies showed that the predominant structure of the modified DNA in sodium phosphate (pH 7) buffer in the absence of Mg2+ was a hairpin containing a 7-nucleotide loop and a stem composed of 3 stable base pairs. In the Mg(2+)-stabilized conformation, the loop became a two-base turn due to the formation of two additional base pairs across the loop.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445839 TI - The role of 5-methylcytidine in the anticodon arm of yeast tRNA(Phe): site specific Mg2+ binding and coupled conformational transition in DNA analogs. AB - The tDNA(Phe)AC, d(CCAGACTGAAGAU13m5C14U15GG), with a DNA sequence similar to that of the anticodon stem and loop of yeast tRNA(Phe), forms a stem and loop structure and has an Mg(2+)-induced structural transition that was not exhibited by an unmodified tDNA(Phe)AC d(T13C14T15) [Guenther, R. H., Hardin, C. C., Sierzputowska-Gracz, H., Dao, V., & Agris, P. F. (1992) Biochemistry (preceding paper in this issue)]. Three tDNA(Phe)AC molecules having m5C14, tDNA(Phe)AC d(U13m5C14U15), d(U13m5C14T15), and d(T13,5C14U15), also exhibited Mg(2+)-induced structural transitions and biphasic thermal transitions (Tm approximately 23.5 and 52 degrees C), as monitored by CD and UV spectroscopy. Three other tDNA(Phe)AC, d(T13C14T15), d(U13C14U15), and d(A7;U13m5C14U15) in which T7 was replaced with an A, thereby negating the T7.A10 base pair across the anticodon loop, had no Mg(2+)-induced structural transitions and only monophasic thermal transitions (Tm of approximately 52 degrees C). The tDNA(Phe)AC d(U13m5C14U15) had a single, strong Mg2+ binding site with a Kd of 1.09 x 10(-6) M and a delta G of -7.75 kcal/mol associated with the Mg(2+)-induced structural transition. In thermal denaturation of tDNA(Phe)AC d(U13m5C14U15), the 1H NMR signal assigned to the imino proton of the A5.dU13 base pair at the bottom of the anticodon stem could no longer be detected at a temperature corresponding to that of the loss of the Mg(2+)-induced conformation from the CD spectrum. Therefore, we place the magnesium in the upper part of the tDNA hairpin loop near the A5.dU13 base pair, a location similar to that in the X-ray crystal structure of native, yeast tRNA(Phe).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445840 TI - Cyclopropane fatty acid synthase of Escherichia coli: deduced amino acid sequence, purification, and studies of the enzyme active site. AB - Cyclopropane fatty acid (CFA) synthase of Escherichia coli catalyzes a modification of the acyl chains of phospholipid bilayers. We report (i) identification of the CFA synthase protein, (ii) overproduction (> 600-fold) and purification to essential homogeneity of the enzyme, and (iii) the amino acid sequence of CFA synthase as deduced from the nucleotide sequence of the cfa gene. CFA synthase was overproduced by use of the T7 promoter/RNA polymerase system under closely defined conditions. The enzyme was readily purified by a two-step procedure requiring only ammonium sulfate fractionation and binding to phospholipid vesicles followed by flotation in sucrose density gradients. The deduced amino acid sequence predicts a protein of 43,913 Da (382 residues) that lacks long hydrophobic segments. The CFA synthase sequence has no significant similarity to known proteins except for sequences found in other enzymes that utilize S-adenosyl-L-methionine. We also report inhibitor studies of the enzyme active site. PMID- 1445841 TI - Effects of mutations near the bacteriochlorophylls in reaction centers from Rhodobacter sphaeroides. AB - Mutations were made in four residues near the bacteriochlorophyll cofactors of the photosynthetic reaction center from Rhodobacter sphaeroides. These mutations, L131 Leu to His and M160 Leu to His, near the dimer bacteriochlorophylls, and M203 Gly to Asp and L177 Ile to Asp, near the monomer bacteriochlorophylls, were designed to result in the placement of a hydrogen bond donor group near the ring V keto carbonyl of each bacteriochlorophyll. Perturbations of the electronic structures of the bacteriochlorophylls in the mutants are indicated by additional resolved transitions in the bacteriochlorophyll absorption bands in steady-state low-temperature and time-resolved room temperature spectra in three of the resulting mutant reaction centers. The major effect of the two mutations near the dimer was an increase up to 80 mV in the donor oxidation-reduction midpoint potential. Correspondingly, the calculated free energy difference between the excited state of the primary donor and the initial charge separated state decreased by up to 55 mV, the initial forward electron-transfer rate was up to 4 times slower, and the rate of charge recombination between the primary quinone and the donor was approximately 30% faster in these two mutants compared to the wild type. The two mutations near the monomer bacteriochlorophylls had minor changes of 25 mV or less in the donor oxidation-reduction potential, but the mutation close to the monomer bacteriochlorophyll on the active branch resulted in a roughly 3-fold decrease in the rate of the initial electron transfer. PMID- 1445842 TI - 13C magic angle spinning NMR study of the light-induced and temperature-dependent changes in Rhodobacter sphaeroides R26 reaction centers enriched in [4' 13C]tyrosine. AB - Solid-state 13C magic angle spinning (MAS) NMR has been used to investigate detergent-solubilized photosynthetic reaction centers of Rhodobacter sphaeroides R26, selectively enriched in [4-13C]-tyrosine. The reaction centers were frozen, in the dark and while subject to intense illumination, and studied at temperatures between approximately 215 and approximately 260 K. The signal consists of at least seven narrow lines superimposed on a broad doublet. The chemical shift anisotropy is similar to that for crystalline tyrosine. The two narrowest resonances, corresponding to signals from individual tyrosines, are 28 +/- 5 Hz wide, comparable to what is observed for quaternary carbons in linearly elastic organic solids. The line width as well as the chemical shift of these signals is essentially independent of temperature. This provides strong evidence for an unusually ordered, well-shielded, and structurally, electrostatically, and thermodynamically stable interior of the protein complex without structural heterogeneities. As the temperature is lowered, additional signal from the labels develops and the natural abundance resonances from the detergent broaden, providing evidence for considerable flexibility at the exterior of the protein complex and in the detergent belt at the higher temperatures. In addition, the NMR provides evidence for an electrostatically uniform and neutral complex, since the total dispersion in isotropic shifts for the labels is < 5 ppm and corresponds to electron density variations of less than 0.03 electronic equivalents with respect to tyrosine in the solid state or in solution. When the sample is frozen while subject to intense illumination, a substantial part of the protein is brought into the charge-separated state P.+QA.-. At least three sharp resonances, including the narrowest lines, are substantially reduced in intensity. It is argued that this effect is caused by the electronic spin density associated with the oxidized primary donor P.+. These results strongly suggest that the environment of the special pair is extremely rigid and question the role of protein conformational distortions during the primary photoprocess. PMID- 1445843 TI - Qy-excitation resonance Raman scattering from the special pair in Rhodobacter sphaeroides reaction centers. Implications for primary charge separation. AB - Qy-excitation resonance Raman (RR) spectra are reported for reaction centers (RCs) from Rhodobacter sphaeroides 2.4.1. The RR spectra were acquired for both chemically reduced and oxidized RCs at 25 and 201 K by using a variety of excitation wavelengths in the range 800-920 nm. This range spans the Qy absorption bands of the special pair (P) and the accessory bacteriochlorophylls (BChls). The RR studies indicate that both P and the accessory BChls exhibit rich RR spectra in the 30-1800-cm-1 region. For both types of pigments, at least 20 bands are observed in the 30-750-cm-1 range. Although the frequencies of the modes of P and the accessory BChls are different, it is possible to make one-to one correlations of the bands observed for the two types of pigments. This result suggests that the vibronically active low-frequency modes of P are derived from monomer-like vibrations (although they may be coupled monomer-like modes) rather than being vibrations resulting from the additional degrees of freedom present in the dimer. A plausible set of vibrational assignments for the low-frequency modes of both P and the accessory BChls is proposed on the basis of a semiempirical normal coordinate calculation. Comparison of the RR intensities of the low frequency modes of P with those of the analogous modes of the accessory BChls indicates that the intensities of the modes of the former pigments are considerably larger than those of the latter. Collectively, the spectral data indicate that a large number of low-frequency modes of P are strongly coupled to the Qy electronic transition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445844 TI - Interaction of CPa-1 with the manganese-stabilizing protein of photosystem II: identification of domains on CPa-1 which are shielded from N-hydroxysuccinimide biotinylation by the manganese-stabilizing protein. AB - The structural organization of photosystem II proteins has been investigated by use of the amino group-labeling reagent N-hydroxysuccinimidobiotin (NHS-biotin) and calcium chloride-washed photosystem II membranes. We have previously shown that the presence of the extrinsic, manganese-stabilizing protein on photosystem II membranes prevents the modification of lysyl residues located on the chlorophyll protein CPa-1 (CP-47) by NHS-biotin [Bricker, T. M., Odom, W. R., & Queirolo, C. B. (1988) FEBS Lett. 231, 111-117]. Upon removal of the manganese stabilizing protein by calcium chloride-washing, CPa-1 can be specifically modified by treatment with NHS-biotin. Preparative quantities of biotinylated CPa 1 were subjected to chemical cleavage with cyanogen bromide. Two major biotinylated peptides were identified with apparent molecular masses of 11.8 and 15.7 kDa. N-terminal sequence analysis of these peptides indicated that the 11.8 kDa peptide was 232G-330M and that the 15.7-kDa peptide was 360P-508V. The 15.7 kDa CNBr peptide was subjected to limited tryptic digestion. The two smallest tryptic fragments identified migrated at apparent molecular masses of 9.1 (nonbiotinylated) and 7.5 kDa (biotinylated). N-terminal sequence analysis and examination of the predicted amino acid sequences of these peptides suggest that the 9.1-kDa fragment was 422R-508V and that the 7.5-kDa fragment was 360P-421A. These results strongly suggest that two NHS-biotinylated domains, 304K-321K and 389K-419K, become exposed on CPa-1 when the manganese-stabilizing protein is removed by CaCl2 treatment. Both of these domains lie in the large extrinsic loop E of CPa-1. PMID- 1445845 TI - Photosystem II function and integrity in spite of drastic protein changes in a conserved region of the D2 protein. AB - D1 and D2 are structurally related proteins forming the core of the photosystem II reaction center. The two proteins have several loop regions including an extended stroma-exposed loop between transmembrane helix D and parallel helix de. This loop (the D-de loop) is phylogenetically conserved in both proteins. The role of the D-de loop in photosystem II was studied in Synechocystis sp. PCC 6803 by constructing a chimeric D2 protein in which the stroma-exposed loop of D1 replaced that of D2. In one of the transgenic lines, a single-base deletion shifted the reading frame of the chimeric gene leading to loss of D2 accumulation and photosystem II assembly. Selection for spontaneous reversion to photoautotrophy yielded several suppressor mutants, five of which were analyzed. In all, further frameshifts in the inserted loop piece restored the original reading frame allowing readthrough to the normal carboxy terminus. However, the sequences in the restored D-de loop varied widely among the mutants. Changes ranged from a deletion of one amino acid residue to an insertion of 31, while the net charge of the D-de loop increased by up to 12 units. Mutant electron transfer rates and photoautotrophic growth were only mildly affected as compared to wild type. Nevertheless, in all mutants, the hydropathy profile of the stroma-exposed D-de loop region maintained its hydrophilic character including turns in similar locations. We conclude that the stroma-exposed, D-de loop of the D2 protein can accommodate drastic composition and size changes without extensive functional consequences in photosystem II.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445846 TI - Oligomeric properties of alpha-dendrotoxin-sensitive potassium ion channels purified from bovine brain. AB - Neuronal acceptors for alpha-dendrotoxin (alpha-DTX) have recently been purified from mammalian brain and shown to consist of two classes of subunit, a larger (approximately 78,000 M(r)) protein (alpha) whose N-terminal sequence is identical to that of a cloned, alpha-DTX-sensitive K+ channel, and a novel M(r) 39,000 (beta) polypeptide of unknown function. However, little information is available regarding the oligomeric composition of these native molecules. By sedimentation analysis of alpha-DTX acceptors isolated from bovine cortex, two species have been identified. A minority of these oligomers contain only the larger protein, while the vast majority possess both subunits. Based on accurate determination of the molecular weights of these two forms it is proposed that alpha-DTX-sensitive K+ channels exist as alpha 4 beta 4 complexes because this combination gives the best fit to the experimental data. PMID- 1445847 TI - Acidic interaction of the colicin A pore-forming domain with model membranes of Escherichia coli lipids results in a large perturbation of acyl chain order and stabilization of the bilayer. AB - 2H and 31P NMR techniques were used to study the effects on acyl chain order and lipid organization of the well-characterized pore-forming domain of colicin A (20 kDa thermolytic fragment of colicin A) upon insertion in model membrane systems derived from the Escherichia coli fatty acid auxotrophic strain K 1059, which was grown in the presence of [11,11-2H2]-labeled oleic acid. Addition of the protein to dispersions of the E. coli total lipid extract, in a 1/70 molar ratio of peptide to lipids, resulted in a large pH-dependent decrease in quadrupolar splitting of the 2H NMR spectra. The decrease of the quadrupolar splitting obtained at the various pH values was correlated with the pH dependence of the insertion of the protein in monolayer films using the same E. coli lipid extracts. The pK governing the perturbing effects on the order of the fatty acyl chains was around 5, in agreement with the values of the pH-dependent conformational changes of the pore-forming domain of colicin A required for membrane insertion as reported by van der Goot et al. [(1991) Nature 354, 408 410]. 31P NMR measurements show that the bilayer organization remains intact upon addition of the protein to dispersions of lipid extract. Surprisingly, 31P NMR measurements as a function of temperature indicate that the pore-forming domain of colicin A even stabilizes bilayer lipid structure at pH 4. Both the large effect of the protein on acyl chain order and its bilayer-stabilizing activity are indicative of a surface localization of the protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445848 TI - Cell-surface fucosylation and magnetic resonance spectroscopy characterization of human malignant colorectal cells. AB - Proton (1H) magnetic resonance spectroscopy (MRS) has been used to distinguish lowly and highly tumorigenic human malignant colorectal cell lines based on differences in lipid, choline, and fucose resonances. The spectral patterns were comparable with those obtained for human colorectal biopsy specimens, indicating that cells grown in vitro are suitable for documenting colorectal tumor biology. For the first time, two-dimensional (2D) correlation spectroscopy (COSY) has been used to assess the fucosylation state on the surface of intact viable cells, and differences were recorded between the highly and lowly tumorigenic cell lines. Four methyl-methine cross-peaks were assigned to covalently linked fucose on the basis of increases in volume following the addition of free fucose. Both cell lines incorporated the same amount of exogenous free fucose as determined chemically, but the COSY spectra indicated that the fucose was distributed differently by each cell line. Of the four sites containing MR-visible bound fucose, one was common to both cell lines, two characteristic of the highly tumorigenic line, and the remaining site unique to the lowly tumorigenic cells. Material released from the highly tumorigenic cells in response to increased cell density was also fucosylated (whereas shed material from lowly tumorigenic cells was not), suggesting a biological role for shed fucosylated antigens in tumor aggression. PMID- 1445849 TI - Structure of a novel sulfate-containing mycobacterial glycolipid. AB - We described previously the unusual structures of the two major C-mycoside glycopeptidolipids from Mycobacterium fortuitum biovar. peregrinum. More polar glycolipids, potentially more interesting in terms of antigenicity, were also present in the strains. A combination of FAB mass spectrometry, NMR, chemical analyses, and radiolabeling was successfully applied to these glycolipids to arrive at the unexpected and novel structure for the more polar compound. This consisted of the "orthodox" basic structure of the apolar C-mycosides, modified at the alaninol end by the presence of a sulfate group on position 2 of a 3,4-di O-methylrhamnosyl residue. This novel and second class of sulfate-containing mycobacterial glycolipid may provide a chemical basis for the differentiation and classification of members of the M. fortuitum complex, the main group causing human diseases among the many fast-growing mycobacteria widely distributed in nature. PMID- 1445850 TI - Regulation of the concentration of pre beta high-density lipoprotein in normal plasma by cell membranes and lecithin-cholesterol acyltransferase activity. AB - A minor fraction of plasma high-density lipoprotein (pre beta-1 HDL) has been shown to promote cholesterol efflux from peripheral cell membranes [Castro, G. R., & Fielding, C. J. (1988) Biochemistry 27, 25-29]. When isolated native plasma is incubated at 37 degrees C, this fraction is specifically decreased. On the other hand, the level of plasma pre beta-1 HDL is fully protected in the presence of even very low levels of fibroblasts, vascular smooth muscle cells, or macrophages. Blood cells were completely inactive in maintaining plasma pre beta 1 HDL levels in the absence of peripheral cells, even at the relatively high levels present in whole blood. The loss of pre beta-1 observed in isolated plasma was dependent upon lecithin-cholesterol acyltransferase (LCAT) activity. These data suggest that reverse cholesterol transport catalyzed by pre beta-1 HDL, and subsequent LCAT-mediated cholesterol esterification, is directly dependent upon the interaction between this HDL species and competent peripheral cells. PMID- 1445851 TI - Interactions of retinol with binding proteins: studies with retinol-binding protein and with transthyretin. AB - The interactions within the molecular complex in which retinol circulates in blood were studied. To monitor binding between retinol-binding protein (RBP) and transthyretin (TTR), TTR was labeled with a long-lived fluorescence probe (pyrene). Changes in the rotational volume of TTR following its association with RBP were monitored by fluorescence anisotropy of the probe. Titration of TTR with holo-RBP revealed the presence of 1.5 binding sites characterized by a dissociation constant Kd = 0.07 microM. At 0.15 M NaCl, binding of RBP to TTR showed an absolute requirement for the native ligand, retinol. At higher ionic strength (0.5 M NaCl), RBP complexed with retinal also bound to TTR with high affinity (Kd = 0.134 microM). RBP containing retinoic acid did not bind to TTR even at the high salt concentration. The data suggest that the TTR binding site on RBP is in close proximity to the retinoid binding site and that the head group of retinoic acid, when bound to RBP, presents steric hindrance for the interactions with TTR. The implications of the data for selectivity in retinoid transport in the circulation are discussed. The kinetics of the steps leading to complete dissociation of the retinol-RBP-TTR complex was also studied. The first step of this process was dissociation of retinol, which had a rate constant of 0.06/min. Following loss of retinol, the two proteins dissociate. The rate of dissociation is slow (k = 0.055/h), however, indicating that the complex apo-RBP TTR will be an important factor in regulating serum levels of retinol. PMID- 1445852 TI - Mechanism of binding of the new antimitotic drug MDL 27048 to the colchicine site of tubulin: equilibrium studies. AB - MDL 27048 [trans-1-(2,5-dimethoxyphenyl)-3-[4-(dimethylamino)phenyl]-2- methyl-2 propen-1-one] fluoresces when bound to tubulin but not in solution. This effect has been investigated and found to be mimicked by viscous solvents. Therefore, MDL 27048 appears to be a fluorescent compound whose intramolecular rotational relaxation varies as a function of microenvironment viscosity. The binding parameters of MDL 27048 to tubulin have been firmly established by fluorescence of the ligand, quenching of the protein fluorescence, and gel equilibrium chromatography. The apparent binding equilibrium constant was (2.75 +/- 0.45) x 10(6)M-1, and the binding site number was 0.81 +/- 0.12 (10 mM sodium phosphate 0.1 mM GTP, pH 7.0, at 25 degrees C). The binding is exothermic. The binding of MDL 27048 overlaps the colchicine and podophyllotoxin binding sites. Binding of MDL 27048 to the colchicine site was also measured by competition with MTC [2 methoxy-5-(2,3,4-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-one] , a well characterized reversibly binding probe of the colchicine site [Andreu et al. (1984) Biochemistry 23, 1742-1752; Bane et al., (1984) J. Biol. Chem. 259, 7391 7398]. In contrast with close analogues of colchicine, MDL 27048 and podophyllotoxin neither affected the far-ultraviolet circular dichroism spectrum of tubulin, within experimental error, nor induced tubulin GTPase activity. Like podophyllotoxin, an excess of MDL 27048 over tubulin induced no abnormal cooperative polymerization of tubulin, which is characteristic of colchicine binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445853 TI - Fluorescence stopped-flow study of the interaction of tubulin with the antimitotic drug MDL 27048. AB - The kinetics of the binding of MDL 27048 to tubulin have been studied by fluorescence stopped flow. The binding is accompanied by a fluorescence increase. The time course can be described by a sum of two exponentials, assumed to be due to the presence of two major tubulin isoforms. The observed rate constants depend in a nonlinear way on the concentration of MDL in pseudo-first-order conditions. This concentration dependence can be described by the presence of a fast equilibrium of low affinity, followed by an isomerization of the initial complex. The dissociation kinetics have been studied by displacement experiments, in which MTC was used as a competitive ligand. The reaction enthalpy change for the first binding equilibrium and the activation energies for the forward and reverse steps of the isomerization were determined from the temperature dependence. This was possible for the two tubulin isotype populations. The kinetics of the binding of MDL to tubulin are slowed down in the presence of 3',4',5' trimethoxyacetophenone, a fast binding analog of the colchicine A-ring, but are not influenced by the binding of tropolone methyl ether, indicating that the binding site of MDL has the A-subsite in common with colchicine, but not the C subsite. PMID- 1445854 TI - Rat insulin-degrading enzyme: cleavage pattern of the natriuretic peptide hormones ANP, BNP, and CNP revealed by HPLC and mass spectrometry. AB - The degradation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) by insulin-degrading enzyme (IDE) has been investigated. As revealed by high-performance liquid chromatography, all three peptides are sequentially cleaved at a limited number of sites, the latter of which were identified by mass spectrometric analyses. The studies revealed that ANP is preferred as substrate over BNP and CNP. ANP degradation is rapidly initiated by hydrolysis at the Ser25-Phe26 bond. Three additional cleavage sites were identified in ANP after prolonged incubation with IDE; in contrast, three and two bonds were hydrolyzed in BNP and CNP, respectively. Analysis of the nine cleavage sites shows a preference for basic or hydrophobic amino acid residues on the carboxyl side of a cleaved peptide bond. In contrast to most of the peptide fragments generated by IDE activity, the initial ANP cleavage product, F-R-Y, is rapidly degraded further by cleavage of the R-Y bond. Cross-linking studies with 125I-ANP in the presence of sulfhydryl-modifying agent indicate that IDE activity is inhibited at the level of initial substrate binding whereas metal-ion chelating agents only prevent hydrolysis. On the basis of its structural and enzymatic properties, IDE exhibits striking similarity to a number of recently described endopeptidases. PMID- 1445855 TI - Determination of the solution structure of a platelet-adhesion peptide of von Willebrand factor. AB - Two-dimensional nuclear magnetic resonance (NMR) spectroscopy in combination with distance geometry (DG) and dynamical simulated annealing (DSA) calculations have been used to determine the tertiary solution structure of a synthetic 29-residue fragment of von Willebrand factor (vWF). This fragment (D514-E542) represents an adhesion site on vWF for its platelet receptor, the glycoprotein Ib-IX complex (GP Ib-IX). The NMR data yielded 109 interproton distance measurements and two chi 1 dihedral angle constraints for use in DG and DSA calculations. Most prominent in the calculated family of solution structures was an amphipathic, right-handed alpha-helix in the C-terminal segment of the peptide. We propose that this highly structured region may be important for the specific molecular interaction of vWF with the GP Ib-IX complex. PMID- 1445856 TI - Perturbation of the equilibrium between open and closed conformations of the periplasmic C4-dicarboxylate binding protein from Rhodobacter capsulatus. AB - A kinetic and thermodynamic analysis has been carried out on the conformational transitions of the periplasmic C4-dicarboxylate binding protein (DctP) from the photosynthetic bacterium Rhodobacter capsulatus. This protein is distinct from other periplasmic binding proteins characterized to date in that the transition between the putative closed-unliganded (BP1) and open-unliganded (BP2) conformations is slow compared to the rate of ligand binding [Walmsley, A. R., Shaw, J. G., & Kelly, D. J. (1992) J. Biol. Chem. 276, 8064-8072]. Using stopped flow fluorescence techniques, we have probed the conformational dynamics of the closed to open transition of DctP in the absence and presence of ligand. Both the forward rate constant for the BP1 to BP2 interconversion (k1) and the fumarate dissociation rate constant (k-3) were found to increase in a biphasic manner between pH 5 and pH 11. The data were fitted to a two-pKa function which gave pKa values of 10.3 and 5.4 for the BP1 to BP2 interconversion and 8.9 and 4.5 for the closed-liganded (BP3L) to open-liganded (BP2L) transition. An increase in ionic strength at constant pH resulted in a hyperbolic increase in both k1 and k-3 to maximal rates that were similar in each case to the values obtained in pH variation experiments. Measurement of the temperature dependencies of k1 and k-3 also gave similar activation energies. Gibbs free energy, enthalpy, and entropy changes were determined for the open to closed transitions of DctP in both the presence and absence of ligand.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445857 TI - Cooperative oxygen binding, subunit assembly, and sulfhydryl reaction kinetics of the eight cyanomet intermediate ligation states of human hemoglobin. AB - Correlations between the energetics of cooperativity and quaternary structural probes have recently been made for the intermediate ligation states of Hb [Daugherty et al. (1991) Proc. Natl. Acad. Sci. US 88, 1110-1114]. This has led to a "molecular code" which translates configurations of the 10 ligation states into switch points of quaternary transition according to a "symmetry rule"; T-->R quaternary structure change is governed by the presence of at least one heme-site ligand on each of the alpha beta dimeric half-molecules within the tetramer [see Ackers et al. (1992) Science 255, 54-63, for summary]. In order to further explore this and other features of the cooperative mechanism, we have used oxygen binding to probe the energetics and cooperativities for the vacant sites of the cyanomet ligation species. We have also probed structural aspects of all eight cyanomet ligation intermediates by means of sulfhydryl reaction kinetics. Our oxygen binding results, obtained from a combination of direct and indirect methods, demonstrate the same combinatorial aspect to cooperativity that is predicted by the symmetry rule. Overall oxygen affinities of the two singly ligated species (alpha +CN beta)(alpha beta) and (alpha beta +CN)(alpha beta) were found to be identical (pmedian = 2.4 Torr). In contrast, the doubly-ligated species exhibited two distinct patterns of oxygen equilibria: the asymmetric species (alpha +CN beta +CN)(alpha beta) showed very high cooperativity (nmax = 1.94) and low affinity (pmedian = 6.0 Torr), while the other three doubly-ligated species showed diminished cooperativity (nmax = 1.23) and considerably higher oxygen affinity (pmedian = 0.4 Torr). Extremely high oxygen affinities were found for the triply-ligated species (alpha +CN beta +CN)(alpha beta +CN) and (alpha +CN beta +CN)(alpha +CN beta) (pmedian = 0.2 Torr). Their oxygen binding free energies are considerably more favorable than those of the alpha and beta subunits within the dissociated alpha beta dimer, demonstrating directly the quaternary enhancement effect, i.e., enhanced oxygen affinity at the last binding step of tetramer relative to the dissociated protomers. Oxygen binding free energies measured for the alpha subunit within the isolated (alpha beta +CN) dimer and for the beta subunit within the isolated (alpha +CN beta) dimer sum to the free energy for binding two oxygens to normal hemoglobin dimers (-16.3 +/- 0.2 versus -16.7 +/- 0.2, respectively), arguing against cooperativity in the isolated dimer. Correlations were established between cooperative free energies of the 10 cyanomet ligation microstates and the kinetics for reacting their free sulfhydryl groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1445858 TI - Temperature and guanidine hydrochloride dependence of the structural stability of ribonuclease T1. AB - The thermal unfolding of ribonuclease T1 has been studied by high-sensitivity differential scanning calorimetry as a function of temperature, [GuHCl], and scanning rate. The destabilizing effect of GuHCl has revealed that the kinetics of the unfolding transition become extremely slow as the transition temperature decreases. At pH 5.3 and zero GuHCl, the unfolding transition is centered at 59.1 degrees C; upon increasing the GuHCl concentration, the transition occurs at lower temperatures and exhibits progressively slower kinetics; so, for example, at 3 M GuHCl, the transition temperature is 40.6 degrees C and is characterized by a time constant close to 10 min. Under all conditions studied (pH 5.3, pH 7.0, [GuHCl] < 3 M), the transition is thermodynamically reversible. The slow kinetics of the transition induce significant distortions in the shape of the transition profiles that can be mistakenly interpreted as deviations from a two-state mechanism. Determination of the thermodynamic parameters from the calorimetric data has required the development of an analytical formalism that explicitly includes the thermodynamics as well as the kinetics of the transition. Using this formalism, it is shown that a two-state slow-kinetics model is capable of accurately describing the structural stability of ribonuclease T1 as a function of temperature, GuHCl concentration, and scanning rate. Multidimensional analysis of the calorimetric data has been used to estimate the intrinsic thermodynamic parameters for protein stability, the interaction parameters with GuHCl, and the time constant for the unfolding transition and its temperature dependence. PMID- 1445859 TI - The hydrophobic core of Escherichia coli thioredoxin shows a high tolerance to nonconservative single amino acid substitutions. AB - A set of single amino acid substitutions has been constructed at positions Leu42 and Leu78 in the hydrophobic core of Escherichia coli thioredoxin. This protein is required for the in vivo assembly of filamentous bacteriophages such as M13. Almost all the mutants retain this activity regardless of the change in size, hydrophobic nature, or charge of the substitution. Determination of the free energies of unfolding of the mutants containing charged residues shows that these are significantly destabilized as would be expected from simple considerations of the hydrophobic effect. Thioredoxin therefore represents a class of proteins where the often observed correlation between a particular biological activity and thermodynamic stability is not evident for single mutants in the all-or-none assay used. Native thioredoxin is very stable. Thus, structurally single mutants may not perturb the folding equilibrium or the dynamic behavior sufficiently for the effects to be sensed in vivo. PMID- 1445860 TI - Synthesis of 3'-C-methyladenosine and 3'-C-methyluridine diphosphates and their interaction with the ribonucleoside diphosphate reductase from Corynebacterium nephridii. AB - Two nucleoside diphosphate analogs, 3'-C-methyl-ADP and 3'-C-methyl-UDP, have been tested as substrate and/or allosteric effectors using the adenosylcobalamin dependent ribonucleoside diphosphate reductase of Corynebacterium nephridii. Neither analog was a substrate for the reductase. However, they did function as allosteric effectors and as inhibitors of the reduction of ADP and UDP, respectively. The nucleotide analogs did not stimulate the hydrogen exchange reaction between [5'-3H2]adenosylcobalamin and the solvent, indicating that the cleavage of the 3'-carbon-hydrogen bond is a prerequisite for the exchange reaction. A reinvestigation of the requirements for the exchange reaction revealed that the deoxyribonucleoside diphosphate products are very effective promoters of this reaction. Indeed, the deoxyribonucleoside diphosphates were found to be more effective in promoting the exchange reaction than the ribonucleoside diphosphate substrates. In contrast, the deoxyribonucleoside triphosphate effectors, dATP, dUTP, and dTTP, were only marginally effective as promoters of this reaction. PMID- 1445861 TI - Role of serine 214 and tyrosine 171, components of the S2 subsite of alpha-lytic protease, in catalysis. AB - The function of a hydrogen bond network, comprised of the hydroxyl groups of Tyr 171 and Ser 214, in the hydrophobic S2 subsite of alpha-lytic protease, was investigated by mutagenesis and the kinetics of a substrate analog series. To study the catalytic role of the Tyr 171 and Ser 214 hydroxyl groups, Tyr 171 was converted to phenylalanine (Y171F) and Ser 214 to alanine (S214A). The double mutant (Y171F: S214A) also was generated. The single S214A and double Y171F:S214A mutations cause differential effects on catalysis and proenzyme processing. For S214A, kcat/Km is (4.9 x 10(3))-fold lower than that of wild type and proenzyme processing is blocked. For the double mutant (Y171F:S214A), kcat/Km is 82-fold lower than that of wild type and proenzyme processing occurs. In Y171F, kcat/Km is 34-fold lower than that of wild type, and the proenzyme is processed. The data indicate that Ser 214, although conserved among serine proteases and hydrogen bonded to the catalytic triad [Brayer, G. D., Delbaere, L. T. J., & James, M. N. G. (1979) J. Mol. Biol. 131, 743], is not essential for catalytic function in alpha-lytic protease. A substrate series (in which peptide length is varied) established that the mutations (Y171F and Y171F:S214A) do not alter enzyme substrate interactions in subsites other than S2. The pH dependence of kcat/Km for Y171F and Y171F:S214A has changed less than 0.5 unit from that of wild type; this suggests the catalytic triad is unperturbed. In wild type, hydrophobic interactions at S2 increase kcat/Km by up to (1.2 x 10(3))-fold with no effect on Km.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445862 TI - Purification and characterization of the human stromelysin catalytic domain expressed in Escherichia coli. AB - Human stromelysin is a member of the matrix metalloproteinase family involved in connective tissue degradation. The stromelysin catalytic domain (SCD) lacking both propeptide and C-terminal fragment was expressed in Escherichia coli in soluble and insoluble forms. The insoluble SCD was refolded to the active form in high yield. The protein showed remarkable thermal stability and was able to cleave a thiopeptolide substrate and its natural substrate proteoglycan. The stable and active 20-kDa protein provides an opportunity to elucidate the structure as well as the mechanism of catalysis and inhibition for matrix metalloproteinases. PMID- 1445863 TI - Energy transfer (deazaflavin-->FADH2) and electron transfer (FADH2-->T <> T) kinetics in Anacystis nidulans photolyase. AB - DNA photolyases catalyze the photocycloreversion of cyclobutane pyrimidine dimers. The enzyme from the cyanobacterium Anacystis nidulans contains two chromophores, 1,5-dihydroflavin adenine dinucleotide (FADH2) and 7,8-didemethyl-8 hydroxy-5-deazariboflavin (8-HDF). The photophysical/photochemical reactions leading to DNA repair were investigated by using time-resolved and steady-state fluorescence spectroscopy. It was found that the excited singlet state of 8-HDF transfers energy to FADH2 at a rate of 1.9 x 10(10) s-1 and a quantum yield of 0.98. Using the Forster equation for long-range energy transfer and assuming random orientations of the donor and acceptor the interchromophore distance was calculated to be 15 A. The excited singlet FADH2 which forms either by energy transfer from 8-HDF or by direct absorption of a photon has a lifetime of 1.8 ns in the absence of substrate and 0.14 ns in the presence of the photodimer indicating electron transfer from the FADH2 excited singlet state to the dimer at a rate of 6.5 x 10(9) s-1 and quantum efficiency of 92%. PMID- 1445864 TI - Glutamate 1-semialdehyde aminotransferase: anomalous enantiomeric reaction and enzyme mechanism. AB - Glutamate 1-semialdehyde aminotransferase (GSA-AT) catalyzes near 50% conversion of the racemic mixture of GSA to 5-aminolevulinate (ALA), indicating quantitative use of the L-glutamate-derived natural (S)-enantiomer as substrate. This enzymic reaction has been extensively studied with (R,S)-GSA because it is readily purified in high yields following ozonolysis of racemic 4-vinyl-4-aminobutyric acid. However upon addition of (R,S)-GSA, GSA-aminotransferase is converted to the pyridoxal-P or internal aldimine form (418 nm) and not rapidly cycled back to the original pyridoxamine-P, as predicted by the rate of product (ALA) accumulation. Addition of the putative intermediate, (R,S)-4,5-diaminovalerate (DAVA), eliminates this rapid conversion of the enzyme by (R,S)-GSA to the internal aldimine and stimulates initial rates of ALA synthesis (2-3-fold) and results in corresponding increases in apparent equilibrium concentrations of ALA. These results indicate that DAVA is rate limiting and suggest anomalous reactivity of (R)-GSA. Steady-state and spectral kinetic experiments with individual purified enantiomers confirm anomalous reactivity of (R)-GSA: in the case of (S)-GSA, spectral changes are lesser in amplitude and at least 1 or 2 orders of magnitude more rapid. Only (S)-GSA yielded significant amounts of ALA. Since (R)-GSA is an apparent substrate in the first half-reaction, the resulting (R)-DAVA is either inactive or a poor substrate in the second half-reaction. PMID- 1445865 TI - Iron metabolism--new perspectives in view. PMID- 1445866 TI - Cooperative binding is not required for activation of muscle phosphorylase. AB - Muscle and liver glycogen phosphorylase isozymes differ in their responsiveness to the activating ligand AMP. The muscle enzyme, which supplies glucose in response to strenuous activity, binds AMP cooperatively, and its enzymatic activity becomes greatly enhanced. The liver isozyme regulates the level of blood glucose, and AMP is not the primary activator. In muscle glycogen phosphorylase, the residue proline 48 links two secondary structural elements that bind AMP. This amino acid residue is replaced with a threonine in the liver isozyme; unlike the muscle enzyme, liver binds AMP noncooperatively, and the enzymatic activity is not greatly increased. We have substituted proline 48 in the muscle enzyme with threonine, alanine, and glycine and characterized the recombinant enzymes kinetically and structurally to determine if proline at this position is critical for cooperative AMP binding and activation. Importantly, all of the engineered enzymes were fully activated by phosphorylation, indicating that enzymatic activity was not compromised. Only the mutant enzyme with alanine at position 48 responds like the wild-type enzyme to the presence of AMP, indicating that proline is not absolutely required for full cooperative activation. The substitution of either threonine or glycine at this position, however, creates enzymes that no longer bind AMP cooperatively. The enzyme with threonine at position 48 further mimics the liver enzyme, in that the maximal enzymatic activity is also reduced. Significantly, the glycine substitution caused the enzyme to be fully activated by AMP, although binding was not cooperative. The hyperactivation of the glycine mutant by AMP suggests that the total free energy of activation has decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445867 TI - Tracking conformational states in allosteric transitions of phosphorylase. AB - An intrinsic molecular property of a protein domain can be determined by calculating its principal axes from the inertia tensor matrix. The mass-weighted principal axes can be used to calculate an ellipsoid representing the shape of the protein domain, providing an easy means of visualizing domain movements. Most importantly, the mass-weighted principal axes provide an intuitive means of characterizing domain relationships within a protein, as well as the disposition of domains in different protein conformers. Thus, this method provides a simple, quantitative description of differences of domain positions within various protein structures. We show the utility of this method by characterizing the quaternary and tertiary differences as observed in eight structures of phosphorylated or dephosphorylated glycogen phosphorylase with different effectors bound. This analysis revealed domain movements which were characteristic of the activated phosphorylase structures. The monomers of the phosphorylase dimer were found to move apart by a 2.5-A translation and to rotate apart, in three orthogonal directions, by a minimum of 3.2 degrees. Analysis of the three domains within the phosphorylase monomer showed that both simple and complex domain movements occur and that multiple domain configurations are energetically stable. We suggest that the C-terminal domain of phosphorylase moves along a simple path in the transition from an inactive to active conformation. The direction of translation and rotation is consistent, but the magnitude is variable. In contrast, this analysis showed that the activation domain did not behave as a rigid body, and therefore, the motion of this domain is not as easily characterized. PMID- 1445868 TI - Crystal structure of papain-succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide complex at 1.7-A resolution: noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors. AB - Succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide corresponding to a common sequence of endogenous thiol protease inhibitors is a noncompetitive reversible inhibitor of papain. In order to elucidate the binding mode of the inhibitor at the atomic level, its complex with papain was crystallized at ca. pH 7.0 using the hanging drop method, and the crystal structure was analyzed at 1.7-A resolution. The crystal has space group P2(1)2(1)2(1), with a = 43.09, b = 102.32, c = 49.69 A, and Z = 4. A total of 47,215 observed reflections were collected on the imaging plates using the same single crystal, and 19,833 unique reflections with Fo > sigma (Fo) were used for structure determination and refinement. The papain structure was determined by use of the atomic coordinates of papain previously reported, and then refined by the X-PLOR program. The inhibitor molecule was located on a difference Fourier map and fitted into the electron density with the aid of computer graphics. The complex structure was finally refined to R = 19.6% including 118 solvent molecules. The X-ray analysis of the complex crystal shows that the inhibitor is located at the R-domain side, not in the center of the binding site created by the R- and L-domains of papain. Such a binding mode of the inhibitor explains well the biological behavior that the inhibitor exhibits against papain. Comparison with the structure of papain-stefin B complex indicates that the structure of the Gln-Val-Val-Ala-Gly sequence itself is not necessarily the essential requisite for inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445869 TI - Structural comparison suggests that thermolysin and related neutral proteases undergo hinge-bending motion during catalysis. AB - Crystal structures are known for three members of the bacterial neutral protease family: thermolysin from Bacillus thermoproteolyticus (TLN), the neutral protease from Bacillus cereus (NEU), and the elastase of Pseudomonas aeruginosa (PAE), both in free and ligand-bound forms. Each enzyme consists of an N-terminal and C terminal domain with the active site formed at the junction of the two domains. Comparison of the different molecules reveals that the structure within each domain is well conserved, but there are substantial hinge-bending displacements (up to 16 degrees) of one domain relative to the other. These domain motions can be correlated with the presence or absence of bound inhibitor, as was previously observed in the specific example of PAE [Thayer, M.M., Flaherty, K.M., & McKay, D.B. (1991) J. Biol. Chem. 266, 2864-2871]. The binding of inhibitor appears to be associated with a reduction of the domain hinge-bending angle by 6-14 degrees and a closure of the "jaws" of the active site cleft by about 2 A. Crystallographic refinement of the structure of thermolysin suggests that electron density seen in the active site of the enzyme in the original structure determination probably corresponds to a bound dipeptide. Thus, the crystal structure appears to correspond to an enzyme-inhibitor or enzyme-product complex, rather than the free enzyme, as has previously been assumed. PMID- 1445870 TI - Role of histidine-40 in ribonuclease T1 catalysis: three-dimensionalstructures of the partially active His40Lys mutant. AB - Histidine-40 is known to participate in phosphodiester transesterification catalyzed by the enzyme ribonuclease T1. A mutant enzyme with a lysine replacing the histidine-40 (His40Lys RNase T1) retains considerable catalytic activity [Steyaert, J., Hallenga, K., Wyns, L., & Stanssens, P. (1990) Biochemistry 29, 9064-9072]. We report on the crystal structures of His40Lys RNase T1 containing a phosphate anion and a guanosine 2'-phosphate inhibitor in the active site, respectively. Similar to previously described structures, the phosphate containing crystals are of space group P2(1)2(1)2(1), with one molecule per asymmetric unit (a = 48.27 A, b = 46.50 A, c = 41.14 A). The complex with 2'-GMP crystallized in the lower symmetry space group P2(1), with two molecules per asymmetric unit (a = 49.20 A, b = 48.19 A, c = 40.16 A, beta = 90.26). The crystal structures have been solved at 1.8- and 2.0-A resolution yielding R values of 14.5% and 16.0%, respectively. Comparison of these His40Lys structures with the corresponding wild-type structures, containing 2'-GMP [Arni, R., Heinemann, U., Tokuoka, R., & Saenger, W. (1988) J. Biol. Chem. 263, 15358-15368] and vanadate [Kostrewa, D., Hui-Woog Choe, Heinemann, U., & Saenger, W. (1989) Biochemistry 28, 7692-7600] in the active site, respectively, leads to the following conclusions. First, the His40Lys mutation causes no significant changes in the overall structure of RNase T1; second, the Lys40 side chains in the mutant structures occupy roughly the same space as His40 in the corresponding wild-type RNase T1 structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445871 TI - 4Ca2+.troponin C forms dimers in solution at neutral pH that dissociate upon binding various peptides: small-angle X-ray scattering studies of peptide-induced structural changes. AB - Small-angle X-ray scattering data have been measured for rabbit skeletal muscle troponin C and its complexes with the venom peptides melittin and mastoparan as well as synthetic peptides based on regions of the troponin I sequence implicated in troponin C binding. At the neutral pH used in this study (pH 6.8), troponin C shows a tendency to form dimers in the presence of 4 mol equiv of Ca2+, but is monomeric in solution when 2 or less mol equiv of Ca2+ is present. The 4Ca2+.troponin C dimers dissociate upon binding melittin, mastoparan, and peptides based on residues 96-115, 1-30, and 1-40 in the troponin I sequence. This result suggests that the peptide-binding sites overlap with the regions of contact between troponin C molecules forming a dimer. Like the structurally homologous calcium-binding protein calmodulin, troponin C shows conformational flexibility upon binding different peptides. Upon binding melittin, troponin C contracts in a similar manner to calmodulin when it binds peptides known to form amphiphilic helices (e.g., melittin, mastoparan, or MLCK-I). In contrast, mastoparan binding to troponin C does not result in a contracted structure. The scattering data indicate troponin C also remains in an extended structure upon binding the inhibitory peptides having the same sequence as residues 96-115 in troponin I. PMID- 1445872 TI - NMR studies of defensin antimicrobial peptides. 1. Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1. AB - Two-dimensional nuclear magnetic resonance spectroscopy has been used to make resonance assignments of the proton spectra of two defensin antimicrobial peptides, human neutrophil peptide HNP-1 and rabbit neutrophil peptide NP-2. The secondary structures of these peptides were determined from analysis of the proton-proton NOEs and from the positions of slowly exchanging amide protons. Both peptides contain a long stretch of a double-stranded antiparallel beta-sheet in a hairpin conformation that contains a beta-bulge, a short region of triple stranded beta-sheet, and several tight turns. The NMR results clearly show that HNP-1 forms a dimer or higher order aggregate in solution and that Pro8 exists as a cis peptide bond. The NMR data on these peptides are compared with NMR data for a homologous peptide NP-5 [Bach, A. C., Selsted, M. E., & Pardi, A. (1987) Biochemistry 26, 4389-4397]. Analysis of the conformation-dependent proton chemical shifts shows that it is not possible to confidently judge the structural similarity of the three defensins from chemical shift data alone. However, comparison of the 3JHN alpha coupling constants in NP-2 and NP-5 indicates that the backbone conformations for these peptides are very similar. A more detailed comparison of the solution conformations of the defensins peptides is made in the following paper in this issue where the NMR data are used as input for distance geometry and molecular dynamics calculations to determine the three-dimensional structures of HNP-1 and NP-2. PMID- 1445873 TI - NMR studies of defensin antimicrobial peptides. 2. Three-dimensional structures of rabbit NP-2 and human HNP-1. AB - The solution structure of two homologous naturally occurring antimicrobial peptides, rabbit defensin NP-2 and human defensin HNP-1, have been determined by two-dimensional nuclear magnetic resonance spectroscopy, distance geometry, and restrained molecular dynamics calculations. The structure of these defensins consists of an antiparallel beta-sheet in a hairpin conformation, a short region of triple-stranded beta-sheet, several tight turns, and a loop region that has a well-defined local structure but with a global orientation that is not well defined with respect to the rest of the molecule. The solution structures of these two peptides are compared with the solution and crystal structures of two other homologous defensins. The structures for the defensins are also compared with known structures of other naturally occurring antimicrobial peptides. PMID- 1445874 TI - Mutation of the heme-binding crevice of flavocytochrome b2 from Saccharomyces cerevisiae: altered heme potential and absence of redox cooperativity between heme and FMN centers. AB - Kinetic and thermodynamic properties of yeast flavocytochrome b2 (EC 1.1.2.3) are modified by the product pyruvate, which binds to the flavosemiquinone (FSQ) form of the prosthetic flavin and decreases the thermodynamic driving force for electron transfer from FSQ to heme. Pyruvate inhibits flavocytochrome b2, but the catalytic competence of pyruvate-ligated FSQ in intramolecular electron transfer to heme is unclear; one kinetic study suggested pyruvate prevented this reaction [Tegoni, M, Janot J.-M., & Labeyrie, F. (1990) Eur. J. Biochem. 190, 329-342], while laser flash photolysis indicated pyruvate was essential [Walker, M. C., & Tollin, G. (1991) Biochemistry 30, 5546-5555]. To address this problem, wild-type (WT) and mutant (L36I) flavocytochromes b2 have been expressed in Escherichia coli. Both forms incorporated heme and FMN prosthetic groups and were catalytically active. The mutation L36I was a conservative substitution within the heme-binding crevice and was designed to alter the midpoint potential (Em) of the heme to alter the pyruvate-FSQ/heme equilibrium. Potentiometric titrations yielded Em values (pH 7.0, 25 degrees C) of +8 and -28 mV for WT and L36I forms, respectively. The FMN midpoint potentials in the absence of pyruvate (-58 mV, n = 2) were identical within experimental error in WT and L36I species and were also identical (+5 mV, n = 1) in the presence of pyruvate. These results indicated the absence of redox cooperativity between FMN and heme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445875 TI - Genetic variants in the putidaredoxin-cytochrome P-450cam electron-transfer complex: identification of the residue responsible for redox-state-dependent conformers. AB - Camphor is hydroxylated in Pseudomonas putida by a three-component system comprised of an oxidase, cytochrome P-450cam, and a two-protein electron-transfer chain, putidaredoxin and putidaredoxin reductase [Tyson et al. (1972) J. Biol. Chem. 274, 5777-5784]. The enzymatic removal of putidaredoxin's C-terminal tryptophan is known to cause a much reduced rate of enzymatic activity in the reconstituted camphor hydroxylase system [Sligar et al. (1974) Proc. Natl. Acad. Sci. U.S.A. 71, 3906-3910]. To further study the role of tryptophan in the association and/or electron-transfer reactions of putidaredoxin, the gene coding for the iron-sulfur protein was altered so that the tryptophan codon was either deleted or replaced by Phe, Tyr, Asp, Leu, Val, or Lys. Although the initial evaluation of these variant proteins [Davies et al. (1990) J. Am. Chem. Soc. 112, 7396-7398] showed much reduced velocities of electron transfer between P-450cam and the nonaromatic C-terminal proteins, the relative contributions of the binding specificity and intracomplex electron-transfer rates were not addressed. We report here a complete kinetic characterization of these proteins where the dependence of the rate constant on the putidaredoxin concentration was used to determine the intracomplex electron-transfer rate constants and the association energies for all the putidaredoxins in both oxidation states. The sum of forward and reverse intracomplex electron-transfer rate constants varies from 4.90 s-1 for the Lys C-terminal variant to 172 s-1 for the native protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445876 TI - A kinetic study of the folding of staphylococcal nuclease using size-exclusion chromatography. AB - The kinetics of the hydrodynamic volume change accompanying the reversible unfolding of staphylococcal nuclease have been observed by size-exclusion chromatography at 4 degrees C and pH 7.0 using the denaturant guanidine hydrochloride. The observed chromatographic profiles have been simulated by a six component unfolding/refolding mechanism using a consistent set of equilibrium and kinetic parameters. The native protein is an equilibrium mixture of the cis and trans isomers of the peptide bond preceding proline-117. The native conformation containing the cis isomer dominates the equilibrium mixture, is more stable, and unfolds more slowly at its transition midpoint. The denatured protein is an equilibrium mixture of at least four components, the cis/trans isomers of proline 117 and one of the five remaining prolines. The dominant refolding pathway is initiated from the denatured component containing the trans isomer of proline 117. The six-component mechanism is consistent with tryptophan fluorescence kinetic measurements of the wild-type protein and with chromatographic measurements of a mutant P117G protein. PMID- 1445877 TI - Slowly interchanging conformers of bovine neurophysin-I in the unliganded dimeric state. AB - The effect of neurophysin dimerization on Tyr-49, a residue adjacent to the hormone-binding site, was investigated by proton NMR in order to analyze the basis of the dimerization-induced increase in neurophysin hormone affinity. Dimerization-induced changes in Tyr-49 resonances, in two unliganded bovine neurophysins, suggested that Tyr-49 perturbation is an intrinsic consequence of dimerization, although Tyr-49 is distant from the monomer-monomer interface in the crystalline liganded state. To determine whether this perturbation reflects a conformational difference between liganded and unliganded states that places Tyr 49 at the interface in the unliganded state, or a dimerization-induced change in secondary (2 degrees) or tertiary (3 degrees) structure, the more general structural consequences of dimerization were further analyzed. No change in 2 degrees structure upon dimerization was demonstrable by CD. On the other hand, a general similarity of regions involved in dimerization in unliganded and liganded states was indicated by NMR evidence of participation of His-80 and Phe-35 in dimerization in the unliganded state; both residues are at the interface in the crystal structure and distant from Tyr-49. Consistent with a lack of direct participation of Tyr-49 at the monomer-monomer interface, dimerization induced at least two distinct slowly exchanging environmental states for the 3.5 ring protons of Tyr-49 without significantly increased dipolar broadening relative to the monomer. Two environments were also found in the dimer of des-1-8 neurophysin I for the methyl protons of Thr-9, another residue distant from the monomer monomer interface and close to the binding site in the liganded state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445878 TI - Identification of the ubiquinone-binding site of NADH:ubiquinone oxidoreductase (complex I) from Neurospora crassa. AB - In order to localize the ubiquinone-binding site of complex I (NADH:ubiquinone oxidoreductase), a novel photoreactive ubiquinone analogue (Q0C7ArN3) has been synthesized. It is shown that the direct chemical precursor of this analogue (Q0C7ArNO2) and the analogue itself are accepted as substrates in an enzyme assay utilizing ubiquinone-depleted mitochondrial membranes of Neurospora crassa. The activity of the enzyme applying these derivatives is inhibited by 50% at a concentration of 9 and 20 microM rotenone. Photoaffinity labeling experiments were performed with both isolated complex I and whole mitochondrial membranes of N. crassa under various conditions. In each of these experiments a protein subunit with an apparent molecular mass of about 9.5 kDa was labeled with high specificity. Radioactive labeling was totally prevented by the addition of ubiquinone-2 at concentrations higher than 500 microM but was not affected by comparable concentrations of rotenone or other hydrophobic substances. In the labeling experiments using whole membranes, the labeling signal was dramatically increased in the presence of 1.5 mM NADH. These results strongly suggest that the ubiquinone analogue interacts specifically with the enzyme. PMID- 1445879 TI - Characterization of the 9.5-kDa ubiquinone-binding protein of NADH:ubiquinone oxidoreductase (complex I) from Neurospora crassa. AB - A small polypeptide subunit of the NADH:ubiquinone reductase (complex I) from Neurospora crassa has been identified by photoaffinity labeling to participate in the binding of ubiquinone [Heinrich, H., & Werner, S. (1992) Biochemistry (preceding paper in this issue)]. This polypeptide is further characterized by its primary structure and by an assessment of its localization within complex I. A lambda gt11 cDNA expression library was screened using a specific antibody directed against this individual subunit of complex I. Two groups of clones, coding for polypeptide subunits of the appropriate apparent molecular weight, were isolated. One group was shown to contain the relevant recombinants. The derived amino acid sequence for the 9.5-kDa ubiquinone-binding polypeptide shows a similarity with a putative ubiquinol-binding subunit (also a 9.5-kDa polypeptide) from complex III of bovine heart [Usui, S., Yu, L., & Tu, C.-A. (1990) Biochemistry 29, 4618-4626]. The polypeptide has a hydrophobic stretch of a sufficient length to span the membrane. It resists against extraction with NaBr or Na2CO3, and therefore probably is buried in the so-called hydrophobic membrane portion of complex I. This nuclearly-encoded subunit lacks a typical cleavable presequence and is imported into isolated mitochondria by a membrane potential dependent process. PMID- 1445880 TI - Photooxidation of cytochrome b559 in oxygen-evolving photosystem II. AB - Cytochrome b559 (cyt b559) is an intrinsic and essential component of the photosystem II (PSII) protein complex, but its function, stoichiometry, and electron-transfer kinetics in the physiological system are not well-defined. In this study, we have used flash-detection optical spectroscopy to measure the kinetics and yields of photooxidation and dark reduction of cyt b559 in untreated, O2-evolving PSII-enriched membranes at room temperature. The dark redox states of cyt b559 and the primary electron acceptor, QA, were determined over the pH range 5.0-8.5. Both the fraction of dark-oxidized cyt b559 and dark reduced QA increased with increasing acidity. Consistent with these results, an acid-induced drop in pH from 8.5 to 4.9 in a dark-adapted sample caused the oxidation of cyt b559, indicating a shift in the redox state during the dark reequilibration. As expected from the dark redox state of cyt b559, the rate and extent of photooxidation of cyt b559 during continuous illumination decreased toward more acidic pH values. After a single, saturating flash, the rate of photooxidation of cyt b559 was of the same order of magnitude as the rate of S2QA charge recombination. In untreated PSII samples at pH 8.0 with 42% of cyt b559 oxidized and 15% of QA reduced in the dark, 4.7% of one copy of cyt b559 was photooxidized after one flash with a t1/2 of 540 +/- 90 ms. On the basis of our previous work [Buser, C. A., Thompson, L. K., Diner, B. A., & Brudvig, G. W (1990) Biochemistry 29, 8977] and the data presented here, we conclude that Sn+1, YZ., and P680+ are in redox equilibrium and cyt b559 (and YD) are oxidized via P680+. After a period of illumination sufficient to fully reduce the plastoquinone pool, we also observed the pH-dependent dark reduction of photooxidized cyt b559, where the rate of reduction decreased with decreasing pH and was not observed at pH < 6.4. To determine the direct source of reductant to oxidized cyt b559, we studied the dark reduction of cyt b559 and the reduction of the PQ pool as a function of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) concentration. We find that DCMU inhibits the reduction of cyt b559 under conditions where the plastoquinone pool and QA are reduced. We conclude that QB-. (H+) or QBH2 is the most likely source of the electron required for the reduction of oxidized cyt b559.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1445881 TI - Escherichia coli F1-ATPase can use GTP-nonchaseable bound adenine nucleotide to synthesize ATP in dimethyl sulfoxide. AB - Escherichia coli F1-ATPase contained 3 mol of tightly-bound adenine nucleotide/mol enzyme. A further 3 mol could be loaded by incubation of the enzyme with ATP. The unloaded enzyme was designated as a F1[2,1] type on the basis of the ability of GTP to displace 1 mol of adenine nucleotide/mol of F1 [Kironde, F.A.S., & Cross, R.L. (1986) J. Biol. Chem. 261, 12544-12549]. The loaded enzyme was designated F1[3,3] since GTP could displace 3 of the 6 mol of bound adenine nucleotide/mol of F1. Incubation of F1[2,1], F1[2,0], and F1[3,0] with phosphate in the presence of 30% (v/v) dimethyl sulfoxide led to the synthesis of ATP from endogenous bound ADP. Hydrolysis of newly synthesized ATP occurred on transfer of the F1 from 30% (v/v) dimethyl sulfoxide to an entirely aqueous medium. Thus, synthesis and hydrolysis of ATP can occur at GTP nonchaseable adenine nucleotide binding sites, and these sites in dimethyl sulfoxide are not necessarily equivalent to noncatalytic sites. PMID- 1445882 TI - Site-directed mutagenesis of the CPa-1 protein of photosystem II: alteration of the basic residue pair 384,385R to 384,385G leads to a defect associated with the oxygen-evolving complex. AB - The psbB gene encodes the intrinsic chlorophyll-a binding protein CPa-1 (CP-47), a component of photosystem II in higher plants, algae, and cyanobacteria. Oligonucleotide-directed mutagenesis was used to introduce mutations into a segment of the psbB gene encoding the large extrinsic loop region of CPa-1 in the cyanobacterium Synechocystis sp. PCC 6803. Altered psbB genes were introduced into a mutant recipient strain (DEL-1) of Synechocystis in which the genomic psbB gene had been partially deleted. Initial target sites for mutagenesis were absolutely conserved basic residue pairs occurring within the large extrinsic loop. One mutation, RR384385GG, produced a strain with impaired photosystem II activity. This strain exhibited growth characteristics comparable to controls. However, at saturating light intensities this mutant strain evolved oxygen at only 50% of the rate of the control strains. Quantum yield measurements at low light intensities indicated that the mutant had 30% fewer fully functional photosystem II centers than do control strains of Synechocystis. Immunological analysis of a number of photosystem II protein components indicated that the mutant accumulates normal quantities of photosystem II proteins and that the ratio of photosystem II to photosystem I proteins is comparable to that found in control strains. Upon exposure to high light intensities the mutant cells exhibited a markedly increased susceptibility to photoinactivation. However, Tris treated thylakoid membranes from both the mutant and wild-type exhibited comparable rates of photoinactivation. Thylakoid membranes isolated from RR384385GG exhibited only 15% of the H2O to 2,6-dichlorophenolindophenol electron transport rate observed in wild-type strains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445884 TI - Kinetic properties of enzyme populations in vivo: alkaline phosphatase of the Escherichia coli periplasm. AB - Studies were conducted to determine the role that diffusion may play in the in vivo kinetics of the Escherichia coli periplasmic enzyme, alkaline phosphatase (AP, encoded by the gene pho A). Passive diffusion of solutes, from solution into the periplasm, is thought to occur mainly through porins in the outer membrane. The outer membrane therefore serves as a diffusion barrier separating a population of periplasmic enzymes from bulk substrate. E. coli strains containing a plasmid with the pho A gene linked to the lac promoter were used in this study in order to vary the amount of enzyme per cell. Alkaline phosphatase assays were conducted with intact cells, and the substrate concentration at half-maximum velocity (normally the Km for the enzyme) was determined as a function of enzyme concentration per cell. The results showed that diffusion of substrate to the enzyme caused as much as a 1000-fold change in this parameter, compared to that of purified enzyme. This suggested that diffusion was the rate-limiting step of the enzymatic reaction in these cells. In agreement with this type of reaction, Eadie-Hofstee and Lineweaver-Burk plots were not linear. At their extremes, these plots represented two types of kinetics. At high substrate concentration, equilibrium of substrate between bulk solution and the periplasm was achieved, and the kinetic properties conformed to Michaelis-Menten. At low substrate concentrations, there were a large number of free (unbound) enzymes, and each substrate molecule that entered the periplasm, through the diffusion barrier, resulted in product formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445883 TI - Role of internal thermodynamics in determining hydrogen tunneling in enzyme catalyzed hydrogen transfer reactions. AB - Previous investigations have indicated a role for hydrogen tunneling in the yeast alcohol dehydrogenase catalyzed oxidation of benzyl alcohol [Cha, Y., Murray, C. J., & Klinman, J. P. (1989) Science 243, 1325] and the bovine plasma amine oxidase catalyzed oxidation of benzylamine [Grant, K.L., & Klinman, J. P. (1989) Biochemistry 28,6597]. In the present studies, values of protium to tritium and deuterium to tritium isotope effects and their temperature dependencies have been measured using ring-substituted substrates for yeast alcohol dehydrogenase and bovine plasma amine oxidase, revealing tunneling in each case. The results of these studies indicate that hydrogen tunneling is a general phenomenon and is not limited to enzyme reactions with degenerate energy levels for bound substrates and products. An analysis of internal thermodynamics in the yeast alcohol dehydrogenase reaction shows that tunneling occurs when delta H degrees is endothermic and that the degree of tunneling appears to increase as delta H degrees decreases toward zero. PMID- 1445885 TI - MgATP and fructose 6-phosphate interactions with phosphofructokinase from Escherichia coli. AB - A thermodynamic linked-function analysis is presented of the interactions of MgATP and fructose 6-phosphate (Fru-6-P) with phosphofructokinase (PFK) from Escherichia coli in the absence of allosteric effectors. MgATP and Fru-6-P are shown to bind in random fashion by product inhibition of the back-reaction as well as by the kinetically competent binding of each ligand individually as monitored by the consequent changes in the intrinsic fluorescence of E. coli PFK. When Fru-6-P is saturating, the dissociation of MgATP is sufficiently slow that it cannot achieve a binding equilibrium in the steady state, causing the observed Km (49 microM) to significantly exceed the Kd (1.7 microM) deduced from a thermodynamic linkage analysis. The following features distinguish the interactions of MgATP and Fru-6-P with E. coli PFK: MgATP and Fru-6-P antagonize each other's binding to the enzyme in a saturable manner with an overall apparent coupling free energy equal to +2.5 kcal/mol at 25 degrees C; MgATP induces positive cooperativity in the Fru-6-P binding profile, with the Hill coefficient calculated from the Fru-6-P binding curves reaching a maximum of 3.6 when MgATP is saturating; and MgATP exhibits substrate inhibition at low concentrations of Fru-6-P. Simulations based upon the rate equation pertaining to a two-active site, two-substrate dimer indicate that these features can all result from two independent couplings: an antagonistic MgATP-Fru-6-P coupling extending at least in part between active sites and a MgATP-induced Fru-6-P-Fru-6-P coupling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445886 TI - Roles of residues 129 and 209 in the alteration by cytochrome b5 of hydroxylase activities in mouse 2A P450S. AB - Cytochrome b5 stimulates the coumarin 7-hydroxylation activity of P450coh. A mutation of Arg-129 in P450coh, however, abolishes the stimulation. Moreover, this mutant P450coh binds loosely to cytochrome b5-conjugated Sepharose 4B, whereas wild-type P450coh binds tightly. Consistent with this, the mutation increases the Ka value for b5 binding approximately 6-fold. The identity of residue 209 also alters the stimulation of the activity of P450coh depending on the type of the substrates used and products formed. Coumarin 7-hydroxylation activity is greatly stimulated by cytochrome b5 only when Phe is at position 209, while cytochrome b5 stimulates testosterone hydroxylation activity of P450coh in which Phe, Asn, Ser or Lys substitutes residue 209. P450coh changes its rate of hydrogen peroxide formation depending on the identity of residue 209 and substrate used. Cytochrome b5 decreases the hydrogen peroxide formation of some P450coh whose activities are stimulated by the cytochrome; however, the decrease does not always result in stimulating the activity. The results indicate, therefore, that residues 129 and 209 play different roles in stimulating P450coh activity by cytochrome b5; Arg-129 is a key residue in the cytochrome b5-binding domain and is essential for the stimulation. Residue 209, however, alters the efficiency of electron transport for substrate oxidation as a residue which resides near the sixth ligand of heme and in the substrate-binding site. PMID- 1445887 TI - Donor-acceptor tetrahydrochrysenes, inherently fluorescent, high-affinity ligands for the estrogen receptor: binding and fluorescence characteristics and fluorometric assay of receptor. AB - We have examined the binding behavior and fluorescence characteristics of a series of novel ligands for the estrogen receptor (ER). These ligands are derivatives of 5,6,11,12-tetrahydrochrysene (THC), a structure that embodies a stilbene chromophore, found in many nonsteroidal estrogens, within a rigid tetracyclic system where it cannot easily be distorted from planarity, thus providing the conjugation and rigidity required for efficient fluorescence. Additional steric bulk, as trans-disposed ethyl substituents at the internal C-5 and C-11 positions, is required for the highest relative binding affinity (RBA), and the trans-5,11-diethyl-2,8-dihydroxy-THC derivative binds to ER with an affinity greater than that of estradiol. The replacement of one of the phenolic hydroxyl groups of this THC derivative with an electron-withdrawing group (COMe, COOMe, CONH2, CN, or NO2) yields unsymmetrical THCs with binding affinities 15 40% that of estradiol (E2). The fluorescence emission shifts from about 380 nm for the dihydroxy THC to 475-688 nm for the donor-acceptor THCs. The emission of these donor-acceptor THCs is highly solvatochromic and shifts to longer wavelengths as the solvent polarity increases. In ethanol, the fluorescence quantum yield of the first four of these compounds is high (phi f = 0.43-0.69), but the fifth compound, the nitro-THC, is almost nonemissive in protic solvents. When they are incubated with protein solutions containing ER (approximately 10( 9) M), the emission from the donor-acceptor THCs bound specifically to ER is in the 500-570-nm range, whereas fluorescence from non-receptor-bound fluorophores is in the 425-460-nm range. Thus, fluorescence from these probes bound specifically to ER could be measured under equilibrium conditions as well as after the removal of free and non-receptor-bound material by treatment with charcoal-dextran. This is one of the first demonstrations of ligands whose fluorescence is distinctly different when free, when bound to ER, or when bound to non-receptor proteins. It is also the first demonstration of ER assay by fluorescence under equilibrium conditions. PMID- 1445888 TI - Tissue-specific alternative splicing of the first exon generates two types of mRNAs in human aromatic L-amino acid decarboxylase. AB - Aromatic-L-amino-acid decarboxylase (AADC) is an enzyme that plays an essential role in synthesizing catecholamines and serotonin in neuronal and endocrine tissues. AADC has also been detected in other nonneuronal tissues including liver and kidney, although its physiological role in nonneuronal tissues has not yet been defined. Previously we have cloned a human AADC cDNA from a neuronal tissue (pheochromocytoma) [Ichinose, H., Kurosawa, Y., Titani, K., Fujita, K., & Nagatsu, T. (1989) Biochem. Biophys. Res. Commun. 164, 1024-1030] and the corresponding genomic DNA [Sumi-Ichinose, C., Ichinose, H., Takahashi, E., Hori, T., & Nagatsu, T. (1992) Biochemistry 31, 2229-2238]. Here we present isolation and characterization of AADC cDNA and genomic DNA from a nonneuronal tissue (human liver). The nonneuronal and neuronal AADC mRNAs differed only in the region corresponding to the untranslated first exon. The first exon for the nonneuronal-type mRNA was located 4.2 kilobases upstream to that for the neuronal type mRNA and 22 kilobases from exon 2, to which it is spliced. Determination of the transcription initiation site indicated that the length of the nonneuronal type exon 1 was 200 bp. A TATA box-like motif was located between positions -26 and -20 from the transcription initiation site. These results showed that an alternative usage of the first exon in the 5'-untranslated regions produces two types of mRNAs in AADC and suggested that alternative splicing would regulate the tissue-specific expression of AADC. PMID- 1445889 TI - Requirement of zymogen modification for activation of porcine plasminogen. AB - In physiological salt solutions, porcine plasminogen is refractory to activation by urokinase or trypsin and to proteolysis at Lys77 by plasmin or trypsin. Plasminogen becomes a substrate for urokinase (at Arg560), plasmin (at Lys77), and trypsin (at both bonds) if chloride ion is removed or if 6-aminohexanoate (2.5 mmol/L) is added. Irrespective of salts, activation of des(1-77)plasminogen is as efficient as activation of des(kringle1-4)plasminogen and is inhibited 50% by 2.5 mmol/L 6-aminohexanoate. In solutions lacking chloride or containing 6 aminohexanoate, plasminogen, des(1-77)plasminogen, and des(kringle1-4)plasminogen show no tendency to saturate urokinase in physiologically relevant concentrations (10 mumol/L). The findings are interpreted as indicating that plasminogen requires modification, either by proteolysis or by ligands, for activation. PMID- 1445890 TI - Direct measurement of the weak interactions between a mouse Fc receptor (Fc gamma RII) and IgG1 in the absence and presence of hapten: a total internal reflection fluorescence microscopy study. AB - Total internal reflection fluorescence microscopy (TIRFM) has been used to directly measure the weak dissociation constants of IgG with a mouse IgG receptor (moFc gamma RII) that has been purified and reconstituted into substrate supported planar membranes. Dissociation constants were measured for three different mouse monoclonal anti-dinitrophenyl (DNP) IgG1 antibodies and for polyclonal mouse IgG, in the absence and presence of saturating amounts of hapten (DNP-glycine). The dissociation constant for polyclonal mouse IgG was 3 microM, which agrees well with previous results. The dissociation constants for the three monoclonal antibodies with moFc gamma RII ranged from 2 microM to 3 microM and were not statistically different, suggesting that changes in moFc gamma RII dissociation constants which may exist within the IgG1 subclass are less than the error of the TIRFM measurements (approximately 20%). The measured IgG1-moFc gamma RII dissociation constants were not different for individual monoclonal antibodies in the absence or presence of saturating concentrations of DNP glycine, directly showing that possible allosteric changes which might occur upon hapten binding and affect the equilibrium characteristics of Fc receptor binding are small. This work demonstrates a new approach for quantitatively examining the effects of solution components on weak receptor-ligand interactions. PMID- 1445891 TI - Energetics of thrombin-fibrinogen interaction. AB - The kinetic mechanism of thrombin-fibrinogen interaction has been elucidated by steady-state measurements of synthetic substrate hydrolysis by human alpha thrombin in the presence of human fibrinogen used as a competitive inhibitor and sucrose used as a viscogenic agent. Sucrose greatly affects the FKm for thrombin fibrinogen interaction, without altering the intrinsic properties of the system. Under conditions of pH 7.5 and 0.1 M NaCl, fibrinogen behaves like a sticky substrate for thrombin, with acylation being comparable to dissociation in the temperature range 20-37 degrees C. In the same temperature range, deacylation is much faster than acylation. The van't Hoff enthalpy of binding for thrombin fibrinogen interaction is -24 +/- 3 kcal/mol and the entropy is -55 +/- 11 cal mol-1 deg-1. A chemical compensation effect is present in the binding of fibrinogen and synthetic amide substrates to thrombin, with the delta H and delta G values being linked through a linear relationship. PMID- 1445892 TI - FTIR spectroscopic studies of the conformation and amide hydrogen exchange of a peptide model of the hydrophobic transmembrane alpha-helices of membrane proteins. AB - The conformation and amide hydrogen exchangeability of the hydrophobic peptide Lys2-Gly-Leu24-Lys2-Ala-amide were studied by Fourier transform infrared spectroscopy. In these studies information on the secondary structure of the peptide was obtained from an examination of the contours of both the amide I and amide II absorption bands. The conformationally sensitive amide I and amide II regions of the infrared spectra suggest that the peptide is predominantly alpha helical and that it contains some non-alpha-helical structures which are probably in an extended conformation. Studies of the exchangeability of the amide protons of the peptide indicate that there are two populations of amide protons which differ markedly with respect to their exchangeability with the bulk solvent phase, whether the peptide is dissolved in methanol or dispersed in hydrated lipid bilayers. One population of amide protons is very readily exchangeable, and our data suggest that it arises primarily but not exclusively from the extended regions of the peptide. The other population exchanges very slowly with the bulk solvent and appears to originate entirely from the alpha-helical domain of the peptide. This latter population is virtually unexchangeable when the peptide is dispersed in hydrated phosphatidylcholine bilayers but can be largely exchanged when the peptide is solubilized with methanol. We suggest that this slowly exchanging population of amide protons arises from the central part of the hydrophobic polyleucine core which forms a very stable alpha-helix that would be deeply buried in the hydrophobic domain of hydrated lipid bilayers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445893 TI - Interaction of a peptide model of a hydrophobic transmembrane alpha-helical segment of a membrane protein with phosphatidylcholine bilayers: differential scanning calorimetric and FTIR spectroscopic studies. AB - High-sensitivity differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy were used to study the interaction of a synthetic model hydrophobic peptide, Lys2-Gly-Leu24-Lys2-Ala-amide, and members of the homologous series of n-saturated diacylphosphatidylcholines. In the low range of peptide mole fractions, the DSC thermograms exhibited by the lipid/peptide mixtures are resolvable into two components. One of these components is fairly narrow, highly cooperative, and exhibits properties which are similar to but not identical with those of the pure lipid. In addition, the fractional contribution of this component to the total enthalpy change, the peak transition temperature, and cooperativity decrease with an increase in peptide concentration, more or less independently of acyl chain length. The other component is very broad and predominates in the high range of peptide concentration. These two components have been assigned to the chain-melting phase transitions of populations of bulk lipid and peptide-associated lipid, respectively. Moreover, when the mean hydrophobic thickness of the PC bilayer is less than the peptide hydrophobic length, the peptide-associated lipid melts at higher temperatures than does the bulk lipid and vice versa. In addition, the chain-melting enthalpy of the broad endotherm does not decrease to zero even at high peptide concentrations, suggesting that this peptide reduces but do not abolish the cooperative gel/liquid-crystalline phase transition of the lipids with which it is in contact. Our DSC results indicate that the width of the phase transition observed at high peptide concentration is inversely but discontinuously related to hydrocarbon chain length and that gel phase immiscibility occurs when the hydrophobic thickness of the bilayer greatly exceeds the hydrophobic length of the peptide. The FTIR spectroscopic data indicate that the peptide forms a very stable alpha-helix under all of our experimental conditions but that small distortions of its alpha-helical conformation are induced in response to any mismatch between peptide hydrophobic length and bilayer hydrophobic thickness. These results also indicate that the peptide alters the conformational disposition of the acyl chains in contact with it and that the resultant conformational changes in the lipid hydrocarbon chains tend to minimize the extent of mismatch of peptide hydrophobic length and bilayer hydrophobic thickness. PMID- 1445894 TI - Are membrane enzymes regulated by the viscosity of the membrane environment? AB - We have examined the idea that membrane enzymes are regulated by the viscosity of surrounding lipids using data compiled from the literature for the effect of the change in membrane viscosity ([symbol: see text]) at the gel- to liquid-crystal phase transition on the activities of several enzymes. The analysis was not extended explicitly to the problem of viscosity-dependent regulation of membrane enzymes in liquid-crystalline lipids because of the absence of exact data for values of [symbol: see text] in liquid-crystalline phases of variable composition. For most membrane enzymes studied, energies of activation are discontinuous, while kcat is continuous, at the main-phase transition. We consider that the energy of activation contains terms related to the height of the chemical barrier to reaction and terms due to the mechanical properties of the bilayer, such as the work of expansion during the catalytic cycle and the temperature dependence of [symbol: see text]. We find that the differences in energies of activation, above and below the break points in Arrhenius plots, are orders of magnitude larger than can be accounted for by the above mechanical factors. Thus, discontinuities in energies of activation at the phase transition appear to reflect changes in the chemical barrier to reaction, which is independent of [symbol: see text]. The theorectical analysis indicates too that values of [symbol: see text] for bilayers in the liquid-crystalline phase would have to be several orders of magnitude larger than those for gel phases in order to provide a basis for viscosity-dependent regulation of membrane enzymes in liquid-crystalline phases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445895 TI - Cloning of the gene coding for a human receptor for formyl peptides. Characterization of a promoter region and evidence for polymorphic expression. AB - Recently we reported that, in HL-60 cells, transcription of the formyl peptide receptor (FPR) gene can be up- and downregulated by agents that induce differentiation of HL-60 cells into neutrophils. To begin studying the mechanisms involved in regulation of FPR gene expression, we cloned two human cDNAs and the gene coding for FPR. The genomic clone (pINF14) contained a 14.5-kb insert. A 2.7 kb EcoRI fragment was obtained from pINF14 that hybridized with an FPR open reading frame probe. The EcoRI fragment was sequenced and found to contain an intronless FPR open reading frame. Sequence alignment of the EcoRI genomic fragment with the FPR cDNA revealed that the first 31 bases of 5' untranslated FPR cDNA were not represented in the genomic fragment. Furthermore, a splicing consensus sequence was present in the genomic fragment at the site of divergence with the cDNA sequence. Restriction mapping and Southern blot analysis identified a 121-bp fragment that contained the sequence corresponding to the first 31 bases of 5' untranslated FPR cDNA. An additional (previously undescribed) 15-bp cDNA sequence in the 5' end of FPR were identified using an anchored polymerase chain reaction. This sequence was also contained in the genomic 121-bp fragment. This 121-bp fragment was located 5.2 kb (intron) upstream of the FPR open reading frame. It contained an unusual TATA box and displayed transcriptional activity in vitro and in vivo. Potential binding sites for AP-1 and glucocorticoid receptor were identified upstream of the putative TATA box.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445896 TI - Effects of the presence of an aldehydic abasic site on the thermal stability and rates of helix opening and closing of duplex DNA. AB - The presence of an abasic site in duplex DNA lowers the thermodynamic stability, as monitored by the optical melting temperature, and decreases the rate of imino proton exchange with water, by about an order of magnitude, as monitored by direct measurement of both the exchange lifetimes and the imino proton T1S. The exchange lifetimes of the imino protons with water as a function of base catalyst concentration were analyzed to determine the origin of the effect of the abasic site on imino exchange lifetimes. Analysis of the results showed that the helix opening rate is not significantly changed by the presence of an abasic site. The differences in exchange lifetimes are attributed to a faster helix closing rate in the presence of an abasic site. The faster rate of helix closing may be an important contribution to the stability of abasic sites in duplex DNA to base catalyzed elimination reaction. It is noted that duplex DNAs containing analogues of the aldehydic abasic site apparently do not exhibit these exchange lifetime effects. PMID- 1445897 TI - Base-selective oxidation and cleavage of DNA by photochemical cosensitized electron transfer. AB - A photochemical mechanism for single-strand cleavage of DNA is proposed in which a photoexcited intercalator transfers an electron to an externally bound cosensitizer. Once formed, the oxidized intercalator oxidizes an adjacent base, creating a charge-separated complex from which reactions leading to cleavage of the sugar-phosphate backbone occur in competition with back electron transfer. Using ethidium bromide (EB) as the intercalator and methyl viologen (MV) as the externally bound cosensitizer, a 10-fold enhancement in the rate of single-strand break formation was found in pBR322 DNA over that for EB alone using 488-nm excitation. The rate of cleavage correlated with the amount of MV bound to DNA. In accord with the expected redox properties of the one-electron-oxidized EB and the DNA bases, cleavage occurs selectively at guanines. Although the reaction proceeds in nitrogen-purged solutions, the rate of cleavage in air-saturated solutions was enhanced 2-fold. Treatment of irradiated samples with alkali leads to a 2-fold increase in the yield of single-strand breaks. These results support a mechanism in which cleavage occurs by selective oxidation of guanines in DNA, initiated by photochemical cosensitized electron transfer from intercalated EB to externally bound MV, and may provide a basis for the development of light activated base-selective DNA cleaving agents. PMID- 1445898 TI - Oxygen radical-mediated DNA damage by redox-active Cr(III) complexes. AB - The mechanism of DNA damage induced by Cr(III) complexes is currently unknown even though it is considered to be the ultimate biologically active oxidation state of chromium. In this study, we have employed the Salmonella reversion assay to identify mutagenic Cr(III) complexes. Cyclic voltammetry was used to differentiate the redox kinetics between mutagenic and selected nonmutagenic Cr(III) species. Plasmid relaxation of supercoiled DNA was employed to show in vitro interactions with plasmid DNA and correlate the interactions with the electrochemical behavior and biological activity. The results of this study demonstrate that the mutagenic Cr(III) complexes identified in the Salmonella reversion assay display characteristics of reversibility and positive shifts of the Cr(III)/Cr(II) redox couple consistent with the ability of these Cr(III) complexes to serve as cyclical electron donors in a Fenton-like reaction. These same mutagenic complexes display an ability to relax supercoiled DNA in vitro, presumably by the induction of single-strand breaks. Nonmutagenic complexes were selected to test different ligands to determine how the ligand directs the activity of Cr(III) complexes. All nonmutagenic complexes tested thus far have shown classical irreversibility, more negative reduction potentials, and an inability to relax supercoiled plasmid DNA. These results suggest that the mechanism by which chromium complexes potentiate mutagenesis involves an oxygen radical as an active intermediate. These data also demonstrate the effect of associated ligands with regard to the ability of a metal to generate an active redox center. PMID- 1445899 TI - Substituent position dictates the intercalative DNA-binding mode for anthracene 9,10-dione antitumor drugs. AB - Molecular modeling studies [Islam, S.A., Neidle, S., Gandecha, B.M., Partridge, M., Patterson, L.H., & Brown, J.R. (1985) J. Med. Chem. 28, 857-864] have suggested that anthracene-9,10-dione (anthraquinone) derivatives substituted at the 1,4 and 1,8 positions with-NH(CH2)2NH(CH2CH3)2+ side chains intercalate with DNA with both substituents in the same groove (classical intercalation) while a similarly substituted 1,5 derivative intercalates in a threading mode with one side chain in each groove. Modeling studies also suggested that anthracene-9,10 dione (anthraquinone) derivatives substituted at the 2,6 positions with NHCO(CH2)R (where R is a cationic group) should bind to DNA by the threading mode, and several such derivatives have been synthesized [Agbandjie, M., Jenkins, T.C., McKenna, R., Reszka, A., & Neidle, S. (1992) J. Med. Chem. 35, 1418-1429]. We have conducted stopped-flow kinetics association and dissociation experiments on the interaction of these anthraquinones with calf thymus DNA and with DNA polymers with alternating AT and GC base pairs to experimentally determine the binding mode and how the threading mode affects intercalation rates relative to similarly substituted classical intercalators. The binding modes, determined by analysis of relative rates, energies of activation, and effects of salt concentration on association and dissociation rate constants, agree completely with the modes predicted by molecular modeling methods. Association and dissociation rate constants for the threading mode are approximately a factor of 10 lower than constants for the classical intercalation mode, and the two modes, thus, have similar binding constants. Variations in rate constants for changes in cationic substituents at the 2 and 6 positions of the anthraquinone ring were surprisingly small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445900 TI - Elsamicin A can convert the Z-form of poly[d(G-C)] and poly[(G-m5C)] back to B form DNA. AB - The interaction of poly[(G-C)] and poly[d(G-m5C)] with the antitumor antibiotic elsamicin A, which binds to alternating guanine + cytosine tracts in DNA, has been studied under the B and Z conformations. Both the rate and the extent of the B-to-Z transition are diminished by the antibiotic, as inferred by spectroscopic methods under ionic conditions that otherwise favor the left-handed conformation of the polynucleotides. Moreover, elsamicin converts the Z-form DNA back to the B form. The circular dichroism data indicate that elsamicin binds to poly[d(G-C)] and poly[d(G-m5C)] to form a right-handed bound elsamicin region(s). The transition can be followed by changes of the molar ellipticity at 250 nm, thus providing a convenient wavelength to monitor the Z-to-B conformational change of the polymers as elsamicin is added. The elsamicin A effect might be explained by a model in which the antibiotic binds preferently to a B-form DNA, playing a role as an allosteric effector on the equilibrium between the B and Z conformations, thus favoring the right-handed one. PMID- 1445901 TI - Purification and characterization of a Neu5Ac alpha 2-->6Gal beta 1-->4GlcNAc and HSO3(-)-->6Gal beta 1-->GlcNAc specific lectin in tuberous roots of Trichosanthes japonica. AB - Two lectins were purified from tuberous roots of Trichosanthes japonica. The major lectin, which was named TJA-II, interacted with Fuc alpha 1-->2Gal beta/GalNAc beta 1-->groups, and the other one, which passed through a porcine stomach mucin-Sepharose 4B column, was purified by sequential chromatography on a human alpha 1-antitrypsin-Sepharose 4B column and named TJA-I. The molecular mass of TJA-I was determined to be 70 kDa by sodium dodecyl sulfate gel electrophoresis. TJA-I is a heterodimer of 38-kDa (36-kDa) and 32-kDa (30-kDa) subunits with disulfide linkage(s), and the difference between 38 and 36 kDa, and between 32 and 30 kDa, is due to secondary degradation of the carboxyl-terminal side. It was determined by equilibrium dialysis that TJA-I has four equal binding sites per molecule, and the association constant toward tritium-labeled Neu5Ac alpha 2-->6Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4GlcOT is Ka = 8.0 x 10(5) M-1. The precise carbohydrate binding specificity was studied using hemagglutinating inhibition assay and immobilized TJA-I. A series of oligosaccharides possessing a Neu5Ac alpha 2-->6Gal beta 1-->4GlcNAc or HSO3(-)- >6Gal beta 1-->4GlcNAc group showed tremendously stronger binding ability than oligosaccharides with a Gal beta 1-->4GlcNAc group, indicating that TJA-I basically recognizes an N-acetyllactosamine residue and that the binding strength increases on substitution of the beta-galactosyl residue at the C-6 position with a sialic acid or sulfate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445902 TI - Determination of the glycosylation patterns, disulfide linkages, and protein heterogeneities of baculovirus-expressed mouse interleukin-3 by mass spectrometry. AB - The primary structure of mouse interleukin-3 (IL-3) expressed by recombinant baculovirus-infected silkworm (Bombyx mori) larvae was analyzed by subjecting isolated IL-3 derived peptides to liquid secondary ion mass spectrometry. Two species of IL-3 were isolated from the silkworm hemolymph by reverse-phase high pressure liquid chromatography. The major component has M(r)20-22 x 10(3) as determined by SDS-PAGE. Liquid secondary ion mass spectrometric analysis was carried out on the reduced tryptic and endopeptidase lysyl-C peptides of glycosylated and deglycosylated IL-3. These studies provided evidence that (1) Asn-16 is heterogeneously glycosylated with four different oligosaccharides, (2) Asn-86 is either nonglycosylated or has attached to it one oligosaccharide, (3) the N-glycosylation sites Asn-44 and Asn-51 are not glycosylated, and (4) there is no O-glycosylation. Liquid secondary ion mass spectrometric analysis of the unreduced tryptic peptides provided evidence for disulfide linkages between Cys 140 and Cys-79 or Cys-80 and between Cys-17 and Cys-79 or Cys-80. In comparison to the major component, a minor IL-3 species (M(r) 17-19 x 10(3) by SDS-PAGE) isolated from the hemolymph showed no difference with respect to the glycosylation pattern or the disulfide linkages, but it was cleaved between Ala 127 and Ser-128, and only a disulfide linkage between Cys-140 and Cys-79 or Cys 80 held the molecule together.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445903 TI - Interfacial conformation of dipalmitoylglycerol and dipalmitoylphosphatidylcholine in phospholipid bilayers. AB - Diacylglycerols are minor constituents of membrane lipids, yet are essential in the activation and membrane association of protein kinase C. Solid-state 13C NMR experiments have been used to characterize the orientation of the glycerol backbone of dipalmitoylglycerol (DPG) and dipalmitoylphosphatidylcholine (DPPC) in egg phosphatidylcholine (PC) bilayers. The 13C NMR spectra of both DPG and DPPC specifically 13C-labeled at the sn-2 chain carbonyl exhibit a single narrow resonance (approximately 2 ppm) in liquid-crystalline egg PC bilayers. In contrast, specific 13C-labeling of both the sn-1 and sn-2 chain carbonyls results in an additional broad component (24-32 ppm) with an axially symmetric line shape. These data reveal that DPG has a distinct motionally-averaged structure in PC bilayers that is similar to that of DPPC and is not significantly affected by the absence of the large polar PC headgroup. The NMR line shapes are roughly consistent with the results of previous FTIR and NMR studies that indicate the sn 1 chain extends from the C1 carbon of the glycerol backbone into the hydrophobic interior of the bilayer, while the sn-2 chain first extends parallel to the bilayer surface and incorporates a bend at the ester linkage in order to keep the sn-1 and sn-2 chains parallel. However, the data suggest that the time-averaged orientation of the glycerol backbone is tilted from the bilayer normal, in contrast to the nearly parallel orientation observed in the crystal structures of phosphatidylcholines and phosphatidylethanolamines or the perpendicular orientation observed in the crystal structures of diacylglycerols. PMID- 1445904 TI - Origin of the chlorophyll b formyl oxygen in Chlorella vulgaris. AB - Chlorophyll (Chl) b is an accessory light-harvesting pigment of plants and chlorophyte algae. Chl b differs from Chl a in that the 3-methyl group on ring B of chl a is replaced by a 3-formyl group on Chl b. The present study determined the biosynthetic origin of the Chl b formyl oxygen in in vivo labeling experiments. A mutant strain of the unicellular chlorophyte Chlorella vulgaris, which can not synthesize Chls when cultured in the dark but rapidly greens when transferred to the light, was grown in the dark for several generations to deplete Chls, and then the cells were transferred to the light and allowed to form Chls in a controlled atmosphere containing 18O2. Chl a and Chl b were purified from the cells and analyzed by high-resolution mass spectroscopy. Analysis of the mass spectra indicated that over 76% of the Chl a molecules had incorporated an atom of 18O. For Chl b, 58% of the molecules had incorporated an atom of 18O at one position and 34% of the molecules had incorporated an atom of 18O at a second position. These results demonstrate that the isocyclic ring keto oxygen of both Chl a and Chl b, as well as the formyl oxygen of Chl b, is derived from O2. PMID- 1445905 TI - Structure of the hirulog 3-thrombin complex and nature of the S' subsites of substrates and inhibitors. AB - The X-ray crystallographic structure of the human alpha-thrombin complex with hirulog 3 (a potent, noncleavable hirudin-based peptide of the "hirulog" class containing a beta-homoarginine at the scissile bond), which is isomorphous with that of the hirugen-thrombin crystal structure, was solved at 2.3-A resolution by starting with a model for thrombin derived from the hirugen-thrombin complex and was refined by restrained least squares methods (R = 0.132). Residues of hirulog 3 were well-defined in the electron density, which included most of the pentaglycine linker and the C-terminal helical turn that was disordered in a related structure of thrombin with hirulog 1. The interactions of D-Phe1'-Pro2' beta-homoArg3' with the active site of thrombin were essentially identical to those of related structures of PPACK- (D-Phe-Pro-Arg chloromethyl ketone) and hirulog 1-thrombin, with the guanidinium function of the arginyl P1 residue forming a hydrogen-bonding ion pair with Asp189 of the S1 site. A noticeable shift in the CA atom of beta-homoArg3' due to the methylene insertion displaces the scissile bond from attack by Ser195, thus imparting proteolytic stability to the beta-homoArg hirulog derivative. Resolution of the pentaglycine spacer, linking N- and C-terminal functional domains into a single oligopeptide bivalent inhibitor, permitted delineation of corresponding S' subsites of thrombin. The position of Gly4' (P1') is stabilized by three hydrogen bonds with His57, Lys60F, and Ser195, while the conformational angles maintained in a strained, nonallowed configuration for non-glycyl amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445906 TI - Calcium-linked self-association of human complement C1s. AB - The weight-average molecular weight of C1s, an activated serine protease subcomponent of human complement C1, has been measured by means of sedimentation equilibrium over a wide range of both protein and calcium ion concentrations. The combined data may be accounted for quantitatively by a simple model for Ca(2+) dependent self-association of C1s to a dimer. According to this model, the monomer contains a single Ca2+ binding site with K approximately equal to 3 x 10(5) M-1, and the dimer contains three independent Ca binding sites, two having a Ca2+ affinity lower than that of the monomer (K approximately equal to 3 x 10(4) M-1). The third binding site in the dimer, which presumably lies at the interface between the two amino-terminal alpha domains, has a higher Ca2+ affinity (K approximately equal to 1 x 10(8) M-1) and provides the driving force for C1s dimerization in the presence of calcium. PMID- 1445907 TI - Thrombin is a Na(+)-activated enzyme. AB - The amidase activity of human alpha-thrombin has been studied at steady state as a function of the concentration of several chloride salts, at a constant ionic strength I = 0.2 M. All kinetic steps of the catalytic mechanism of the enzyme have been solved by studies conducted as a function of relative viscosity of the solution. Among all monovalent cations, Na+ is the most effective in activating thrombin catalysis. This effect is observed with different amide substrates and also with gamma-thrombin, a proteolytic derivative of the native enzyme which has little clotting activity but retains amidase activity toward small synthetic substrates. The specific effects observed as a function of Na+ concentration are indicative of a binding interaction of this monovalent cation with the enzyme. The basis of this interaction has been explored by measurements of substrate hydrolysis collected in a three-dimensional matrix of substrate concentration, relative viscosity, and Na+ concentration, keeping the ionic strength constant with an inert cation such as choline or tetraethylammonium. The data have globally been analyzed in terms of a kinetic linkage scheme where Na+ plays the role of an allosteric effector. The properties of the enzyme change drastically upon binding of Na+, with substrate binding and dissociation, as well as deacylation, occurring on a time scale which is 1 order of magnitude faster. The apparent association constants for Na+ binding to the various intermediate forms of the enzyme have all been resolved from analysis of experimental data and are in the range of 50-100 M-1 at 25 degrees C. Studies conducted at different temperatures, in the range 15-35 degrees C, have revealed the enthalpic and entropic components of Na+ binding to the enzyme. The results obtained from steady-state measurements are supported by independent measurements of the intrinsic fluorescence of the enzyme as a function of Na+ concentration at a constant ionic strength I = 0.2 M, over the temperature range 15-35 degrees C. These measurements are indicative of a drastic conformational change of the enzyme upon Na+ binding to a single site. The energetics of Na+ binding derived from analysis of fluorescence measurements agree very well with those derived independently from steady-state determinations. It is proposed that thrombin exists in two conformations, slow and fast, and that the slow-->fast transition is triggered by binding of a monovalent cation. The high specificity in thrombin activation found in the case of Na+ is the result of its higher affinity compared to all other monovalent cations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1445908 TI - Photoreaction of bacteriorhodopsin at high pH: origins of the slow decay component of M. AB - The absorption spectrum of light-adapted purple membrane in 3 M KCl is dependent on temperature even in the room temperature region. Temperature-induced difference spectra at various pH values suggested that the trans isomer of bacteriorhodopsin, bR570, is in thermal and/or photodynamic equilibrium with several different conformers. The major second conformer occurring at neutral pH had the same spectroscopic properties as the 13-cis isomer, and its content at 35 degrees C was estimated to be more than 20%. Heterogeneity in the protein conformation became more significant above pH8, where temperature-induced difference spectra exhibited a negative peak at 580 nm and a positive peak at 296 nm. This absorption change is very similar to that observed upon the formation of the N intermediate, suggesting that an N-like conformer occurs at high pH and temperature. A significant temperature dependence was also seen in the M decay kinetics at high pH, which were described by two decay components; i.e., the fast decaying M (Mf) was predominant at low temperature, but the amplitude of the slow component (M(s)) increased with increasing temperature. It is suggested that M(s) is generated upon excitation of the N-like conformer, in which the residue (Asp 96) usually acting as a proton donor to the Schiff base is deprotonated. The N like conformer could be N itself, because M(s) was enhanced when N was accumulated by background light. A strong correlation between the amplitude of M(s) and the concentration of N was also revealed by the accumulation kinetics of Mf, M(s), and N after the onset of continuous actinic light.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445909 TI - Partial reactions of bacterial D-amino acid transaminase with asparagine substituted for the lysine that binds coenzyme pyridoxal 5'-phosphate. AB - In bacterial D-amino acid transaminase (EC 2.6.1.21) replacement of Lys-145, which is covalently linked to the coenzyme pyridoxal 5'-phosphate in the wild type enzyme, by an Asn residue gave a mutant enzyme (K145N) that slowly performed each half-reaction, as determined by spectral measurements. With the wild-type enzyme, the kinetics of these events were so rapid that pre-steady-state conditions were needed for their determination. The internal aldimine between coenzyme and Lys-145 was rapidly reduced with NaCNBH3 in the wild-type enzyme, whereas in the mutant enzyme the coenzyme, which is not covalently linked to the protein, was more resistant to reduction; the reduced forms of both wild-type and mutant enzymes were inactive. With large amounts of the K145N mutant enzyme and either amino acid or keto acid substrate alone, the formation of some reaction intermediates, i.e., the external aldimine with D-alanine and the ketimine with alpha-ketoglutarate, can be measured by conventional spectroscopy. Suicide substrates also induced slow spectral shifts of the E-PLP form of the enzyme. For the K145N enzyme, exogenous amines affected only the rate of the transaldimination but not the removal of the alpha-proton of the substrate. These results suggest that in the mutant enzyme some amino acid side chain other than Lys-145 performs this function. In order to identify this site, the K145N mutant enzyme was completely inactivated by the radiolabeled suicide substrate D-serine. Peptide mapping of tryptic digests showed that Lys-267 was the modified site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445910 TI - DNA ligase I from Saccharomyces cerevisiae: physical and biochemical characterization of the CDC9 gene product. AB - Genetic studies have previously demonstrated that the Saccharomyces cerevisiae CDC9 gene product, which is functionally homologous to mammalian DNA ligase I, is required for DNA replication and is also involved in DNA repair and genetic recombination. In the present study we have purified the yeast enzyme. When measured under denaturing conditions, Cdc9 protein has a polypeptide molecular mass of 87 kDa. The native form of the enzyme is an 80-kDa asymmetric monomer. Both estimates are in good agreement with the M(r) = 84,406 predicted from the translated sequence of the CDC9 gene. Cdc9 DNA ligase acts via the same basic reaction mechanism employed by all known ATP-dependent DNA ligases. The catalytic functions reside in a 70-kDa C-terminal domain that is conserved in mammalian DNA ligase I and in Cdc17 DNA ligase from Schizosaccharomyces pombe. The ATP analog ATP alpha S inhibits the ligation reaction, although Cdc9 protein does form an enzyme-thioadenylate intermediate. Since Cdc9 DNA ligase exhibited the same substrate specificity as mammalian DNA ligase I, this enzyme can be considered to be the DNA ligase I of S. cerevisiae. There is genetic evidence suggesting that DNA ligase may be directly involved in error-prone DNA repair. We examined the ability of Cdc9 DNA ligase to join nicks with mismatches at the termini. Mismatches at the 5' termini of nicks had very little effect on ligation, whereas mismatches opposite a purine at 3' termini inhibited DNA ligation. The joining of DNA molecules with mismatched termini by DNA ligase may be responsible for the generation of mutations. PMID- 1445911 TI - Substrate specificity of the isoprenylated protein endoprotease. AB - Proteins containing a CAAX motif at their carboxyl termini are subject to isoprenylation at the cysteine residue. Proteolytic trimming of isoprenylated proteins is essential in the activation of these proteins. A microsomal endopeptidase activity has been identified which cleaves all-trans farnesylated cysteine containing tetrapeptides between the modified residue and the adjacent amino acid to liberate the modified cysteine residue and an intact tripeptide. Structure/activity studies are reported here on this endopeptidase activity which are consistent with the premise that this protease is identical to the one normally involved in the cellular isoprenylation pathway. The protease only processes peptides which possess an isoprenyl moiety. Within the isoprenyl series, the enzyme hydrolyzes all-trans-farnesyl-, all-trans-geranylgeranyl-, and geranyl-containing peptides. The protease also recognizes the AAX sequence, because the protease behaves either stereospecifically or stereoselectively with respect to the individual amino acids of the tripeptide. The enzyme only measurably hydrolyzes isoprenylated peptides possessing L-amino acids at C and A. On the other hand, there is a small but measurable hydrolysis of isoprenylated peptides containing a D-amino acid at X. PMID- 1445912 TI - Solvent isotope partitioning: a new kinetic tool for the determination of desorption rates of reactant water from enzyme-substrate complexes in proteases. AB - The rates of desorption of the substrate water from the binary enzyme-H2O and ternary enzyme-H2O-(peptide)substrate complexes for the two hydrolases, porcine pepsin and thermolysin, have been investigated using a novel technique, solvent isotope partitioning. The experimental design of this method was based on the protocol of Rose et al. [Rose, I. A., O'Connell, E. L., Litwin, S., & BarTana, J. (1974) J. Biol. Chem. 249, 5163-5168] wherein the binary enzyme-H2(18)O complex established in the "pulse" solution was diluted into a "chase" solution containing variable concentrations of peptide substrates in a large pool of H2(16)O. The extent of trapping of H2(18)O within the respective E-H2(18)O and E H2(18)O-(peptide)substrate complexes was determined from mass spectrometric analysis of the hydrolytic products. Our data have shown that the substrate water molecule of pepsin is not exclusively retained in the catalytic cycle and it desorbs from the apo- and substrate-bound complexes at rates that are at least 10 and 4 times faster, respectively, than that of product formation. Similarly, the low trapping of H2(18)O in the carboxylic product of the thermolysin reaction is a consequence of the ready desorption of H2(18)O from the ternary E-H2(18)O (peptide)substrate complex and the binary E-H2(18)O complex. We attribute these results to the loss of the reactant water molecule due to desolvation of the enzyme's active site upon substrate binding. PMID- 1445913 TI - Intramolecular subunit interactions between insulin and insulin-like growth factor 1 alpha beta half-receptors induced by ligand and Mn/MgATP binding. AB - We have previously demonstrated that isolated insulin and IGF-1 alpha beta half receptors can be reconstituted into a functional alpha 2 beta 2 hybrid receptor complex [Treadway et al. (1989) J. Biol. Chem. 264, 21450-21453]. In the present study, we have examined this assembly process by determining the effect of ligand occupancy and Mn/MgATP binding on the dimerization of mutant and wild-type insulin and IGF-1 alpha beta half-receptors. IGF-1 or Mn/MgAMPPCP binding to wild type IGF-1 alpha beta half-receptors resulted in the specific assembly of the alpha beta half-receptors into an alpha 2 beta 2 heterotetrameric IGF-1 holoreceptor complex. Similarly, insulin binding to the kinase-deficient mutant (A/K1018) insulin alpha beta half-receptor also resulted in the specific assembly into an alpha 2 beta 2 holoreceptor complex. In contrast, Mn/MgAMPPCP treatment of A/K1018 mutant insulin alpha beta half-receptors did not induce heterotetramer assembly, consistent with the inability of this mutant receptor to bind ATP. The ability of the insulin alpha beta receptors to assemble with the IGF-1 alpha beta half-receptors was used to examine the intermolecular subunit interactions responsible for dimerization. In the presence of Mn/MgAMPPCP, the wild-type insulin and wild-type IGF-1 alpha beta half-receptors were observed to assemble into an insulin/IGF-1 alpha 2 beta 2 hybrid receptor complex. Similarly, a combination of insulin and IGF-1 induced hybrid receptor formation between wild type IGF-1 and A/K1018 mutant insulin alpha beta half-receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445914 TI - An investigation of the sequence-specific interaction of cis diamminedichloroplatinum(II) and four analogues, including two acridine-tethered complexes, with DNA inside human cells. AB - The sequence specificity of DNA damage caused by cis-diamminedichloroplatinum(II) (cisplatin) and four analogues in human (HeLa) cells was studied using Taq DNA polymerase and a linear amplification system. The primer extension is inhibited by the drug-DNA adducts, and hence the sites of these lesions can be analyzed on DNA sequencing gels. The repetitive alphoid DNA was used as the target DNA in human cells. A comparison was made between adduct formation in human cells and in purified DNA. The sequence-specific position and relative intensity of damage was similar in both systems for cisplatin, dichloro(ethylenediammine)platinum(II) (PtenCl2), and N-[3-N-(ethylenediamino)propyl]acridine-4-carboxamidedichloropl atinum(II) (4AcC3PtenCl2). However, no DNA damage could be detected in cells for trans-diamminedichloroplatinum(II) (transPt) or N-[3-N (ethylenediamino)propyl]acridine-2-carboxamide-dichloroplat inum(II) (2AcC3PtenCl2) despite the ability of these latter analogues to damage purified DNA. Cisplatin, PtenCl2, and 4AcC3PtenCl2, which significantly damaged DNA inside cells, also show antitumor activity in mouse models. However, transPt and 2AcC3PtenCl2, which did not detectably damage DNA inside cells, did not show such antitumor activity. This correlation between intracellular DNA damaging ability and in vivo antitumor activity indicates the potential use of the human cells/Taq DNA polymerase/linear amplification technique as a convenient method for screening new cisplatin analogues for useful chemotherapeutic activity. PMID- 1445915 TI - Sequence specificity of psoralen photobinding to DNA: a quantitative approach. AB - The effects of different DNA sequences on the photoreaction of various furocoumarin derivatives was investigated from a quantitative point of view using a number of self-complementary oligonucleotides. These contained 5'-TA and 5'-AT residues, having various flanking sequences. The furocoumarins included classical bifunctional derivatives, such as 8-methoxy- and 5-methoxypsoralen, as well as monofunctional compounds, such as angelicin and benzopsoralen. Taking into an account the thermodynamic constant for noncovalent binding of each psoralen to each DNA sequence, the rate constants for the photobinding process to each fragment were evaluated. The extent of photoreaction is greatly affected by the DNA sequence examined. While sequences of the type 5'-(GTAC)n are quite reactive towards all furocoumarins, 5'-TATA exhibited a reduced rate of photobinding using monofunctional psoralens. In addition terminal 5'-TA groups were the least reactive with 5- and 8-methoxypsoralen, but not with angelicin or benzopsoralen. Also 5'-AT-containing fragments exhibited remarkably variable responses toward monofunctional or bifunctional psoralen derivatives. As a general trend the photoreactivity rate of the former is less sequence-sensitive, the ratio between maximum and minimum being less than 2 for the examined fragments. The same ratio is about 3.4 for 8-methoxypsoralen and 6.2 for 5-methoxypsoralen. This approach, in combination with footprinting studies, appears to be quite useful for a quantitative investigation of the process of covalent binding of psoralens to specific sites in DNA. PMID- 1445916 TI - Secondary structure and interactions of the packaged dsDNA genome of bacteriophage P22 investigated by Raman difference spectroscopy. AB - Vibrational spectra of the double-stranded DNA genome of bacteriophage P22 in packaged and unpackaged states are compared by digital difference Raman spectroscopy. The difference Raman spectrum, which is sensitive to structural changes at the level of < 2% of a given nucleotide type, reveals the effects of packaging upon sugar pucker, glycosyl orientation, phosphodiester geometry, base pairing, base stacking, and the electrostatic environment of DNA phosphate groups. For both packaged and unpackaged states, the experiments were performed on aqueous solutions at 25 degrees C containing effective P22 DNA concentrations of 30-50 mg/mL in 200 mM NaCl + 10 mM MgCl2 + 10 mM Tris at pH 7.5. At the experimental conditions employed, the B-form secondary structure of unpackaged P22 DNA is minimally perturbed by packaging the viral genome in the virion capsid. However, the electrostatic environment of DNA phosphates is dramatically altered with packaging. Specifically, we find the following: (1) C2'-endo sugar pucker and anti glycosyl orientations are conserved for all nucleosides. (2) Watson-Crick base pairing is essentially completely retained. (3) Alternative secondary structures, whether right- (A or C form) or left-handed (Z form), are not evident in either the packaged or unpackaged viral genome. (4) Small Raman hyperchromic effects (< 10%) observed for certain marker bands of dG, dA, and dT in the packaged state of P22 DNA suggest slightly reduced base-stacking interactions with packaging. These are consistent with previously reported UV hyperchromic effects, but the Raman spectrum shows that they are not associated with either base unpairing or strand separation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445917 TI - Secondary structure of the self-cleaving RNA of hepatitis delta virus: applications to catalytic RNA design. AB - A model for the secondary structure of the self-cleaving RNA from hepatitis delta virus was tested. Specific base changes were introduced in each of four regions with the potential for base-pairing (stems I-IV), and for each variant sequence, a rate constant for cleavage was determined. In each stem, mutations that would interfere with Watson-Crick base-pairing also reduced the first-order rate constants by 10-10(4)-fold relative to the unmodified version. Within stems I and II and a shortened form of stem IV, compensatory changes resulted in rates of cleavage equal to or greater than the unaltered ribozyme sequence. Stem III compensatory mutants cleaved faster than the uncompensated mutants although they were not as active as the natural sequence, suggesting additional sequence dependent requirements within this region. Structure probing of RNA containing the stem II mutations provided an independent confirmation of stem II in the ribozyme. The predictive value of the model was tested by designing two trans acting ribozymes which were circularly permuted composites of genomic, antigenomic, and unique sequences. The core of these two catalytic RNAs was the same, but they otherwise differed in that, in one of them, a constraining tetraloop sequence was added to stem II. Both ribozymes catalyzed the trans cleavage of a substrate oligoribonucleotide, thus providing additional evidence for stem II and the proposed structure in general. PMID- 1445918 TI - Amino acid-specific ADP-ribosylation: structural characterization and chemical differentiation of ADP-ribose-cysteine adducts formed nonenzymatically and in a pertussis toxin-catalyzed reaction. AB - ADP-ribosylation is a posttranslational modification of proteins by amino acid specific ADP-ribosyltransferases. Both pertussis toxin and eukaryotic enzymes ADP ribosylate cysteine residues in proteins and also, it has been suggested, free cysteine. Analysis of the reaction mechanisms of cysteine-specific ADP ribosyltransferases revealed that free ADP-ribose combined nonenzymatically with cysteine. L- and D-cysteine, L-cysteine methyl ester, and cysteamine reacted with ADP-ribose, but alanine, serine, lysine, arginine, N-acetyl-L-cysteine, 2 mercaptoethanol, dithiothreitol, and glutathione did not. The 1H NMR spectrum of the product, along with the requirement for both free sulfhydryl and amino groups of cysteine, suggested that the reaction produced a thiazolidine linkage. ADP ribosylthiazolidine was labile to hydroxylamine and mercuric ion, unlike the ADP ribosylcysteine formed by pertussis toxin and NAD in guanine nucleotide-binding (G-) proteins, which is labile to mercuric ion but stable in hydroxylamine. In the absence of G-proteins but in the presence of NAD and cysteine, pertussis toxin generated a hydroxylamine-sensitive product, suggesting that a free ADP ribose intermediate, expected to be formed by the NADase activity of the toxin, reacted with cysteine. Chemical analysis, or the use of alternative thiol acceptors lacking a free amine, is necessary to distinguish the enzymatic formation of ADP-ribosylcysteine from nonenzymatic formation of ADP ribosylthiazolidine, thereby differentiating putative NAD:cysteine ADP ribosyltransferases from NAD glycohydrolases. PMID- 1445919 TI - Conformational properties of the beta(400-436) and beta(400-445) C-terminal peptides of porcine brain tubulin. AB - Two peptides from the C-terminal region of the major beta-tubulin isotype (400 436 and 400-445) that include the critical areas for interaction with MAP2 and tau were examined to determine their conformations in aqueous solution. Despite a high theoretical potential for alpha-helix formation, CD spectroscopy showed that these peptides consisted primarily of random coil with some reverse turn. This was unaffected by the presence of counterions to the negatively charged side chains (Ca2+, Mg2+), but did change when the side-chain charges were neutralized by lowering the pH; under these conditions, the alpha-helix content of the longer peptide rose to 25% and the C-terminal truncated peptide to 15%. The peptides also adopt alpha-helical structure in the presence of trifluoroethanol, the truncated peptide again attaining a lower maximum percentage. The beta(400-445) peptide was also studied by 1-D and 2-D NMR techniques. The results indicate that at pH 5.6 or 7 in an aqueous solution the peptide is extremely flexible and lacks regular secondary structure, consistent with the CD results. Both peptides inhibited microtubule-associated protein-stimulated tubulin assembly, with the longer peptide being about 4 times as inhibitory as the smaller peptide. Neither was inhibitory in the absence of microtubule-associated proteins, indicating that interaction with this species was necessary for inhibition. The greater activity of the longer peptide could be due to the extra negative charges in this peptide and/or the greater tendency of this peptide to form an alpha-helical structure under the appropriate conditions. PMID- 1445920 TI - Calcium-dependent regulation of caldesmon by an 11-kDa smooth muscle calcium binding protein, caltropin. AB - Caldesmon from chicken gizzard muscle has been examined for its ability to interact with caltropin using affinity chromatography and the fluorescent probe acrylodan. The action of caltropin on the inhibitory effect of caldesmon on actomyosin ATPase was also studied. Like calmodulin, caltropin could release the inhibitory effect of caldesmon in the presence of Ca2+. Complete reversal was obtained when 1 mol of caltropin was added per mol of caldesmon. When caldesmon was applied to caltropin-Sepharose in the presence of Ca2+, most of the caldesmon was bound to the column and could be eluted with EGTA, indicating that there is a direct interaction between caldesmon and caltropin. Acrylodan-labeled caldesmon, when excited at 375 nm, had an emission maximum at 504 nm. Addition of caltropin in the presence of Ca2+ resulted in a nearly 50% increase in fluorescence intensity, and this was accompanied by a blue shift in the emission maximum (i.e., lambda em,max 492 nm), suggesting that the probe now occupies a more nonpolar environment. Titration of caltropin with labeled caldesmon indicated a strong affinity for this protein (Kd was in the order of 8 x 10(-8)-2 x 10(-7) M). However, when caltropin was added to labeled caldesmon in the presence of EGTA, there was no indication of any interaction. Caltropin was at least as potent as calmodulin, if not better, in reversing the inhibitory effect of caldesmon in the presence of calcium, making it a potential Ca2+ factor in regulating caldesmon in smooth muscle. PMID- 1445921 TI - Binding of Ca2+ to sulfogalactosylceramide and the sequential effects on the lipid dynamics. AB - Sulfogalactosylceramide (SGC) is a sulfoglycolipid commonly found in epithelial cells and most animal germ cells. Its cellular function in sperm is unknown, although it has been implicated in cation transport in epithelial cells. The purpose of this study was to determine the lipid dynamic effects of Ca2+ binding to SGC. High-pressure Fourier transform infrared spectroscopy was used in this study. Our spectral results showed that Ca2+ bound to the sulfate moiety of SGC. Moreover, Ca2+ binding weakened the hydrogen bonding of the polar head region of SGC and the hydrocarbon chains became more disordered as revealed by an increase in the correlation field splitting pressure of SGC. Consequently, Ca2+ binding to SGC would increase the fluidity of SGC multibilayers. However, the presence of an alpha-hydroxyl group on the SGC fatty acid was found to strengthen the hydrogen bonding of the polar head region and as a consequence reduced the Ca(2+)-enhanced hydrocarbon chain disorder. Experimental approaches, described in this paper, serve as a model for further studies of the effects of Ca2+ binding on the dynamics of membranes containing SGC or other sulfatides. PMID- 1445922 TI - Charge repulsion in the conformational stability of melittin. AB - Electrostatic repulsion between positively charged groups has been suggested to be critical in determining the conformation of melittin. To clarify the role of repulsive forces, we prepared a series of succinylated melittins, an acetylated melittin, and a synthetic melittin mutant, with various degrees of charge repulsion. The conformation of the melittin derivatives was examined by far-UV circular dichroism under various conditions of pH and salt at 20 degrees C. The stability of the tetrameric helical state was found to be dependent on the net charge of the peptides. The charge repulsive forces destabilized the helical state of intact melittin by 600 cal/(charge.mol of tetramer). This value was close to the corresponding one (450 cal/(charge.mol)) obtained for the acidic molten globule of horse cytochrome c [Goto, Y., & Nishikiori, S. (1991) J. Mol. Biol. 222, 679-686], which has a molecular weight and a net charge comparable to those of the tetrameric melittin. Small-angle X-ray scattering of the tetrameric melittin and the molten globule of cytochrome c showed that the two states are also comparable to each other in the radius of gyration. These results suggest that the contribution of electrostatic repulsion to the conformational stability of melittin is similar to that of the molten globule. PMID- 1445923 TI - Three-dimensional nuclear magnetic resonance structures of mouse epidermal growth factor in acidic and physiological pH solutions. AB - The three-dimensional structures of epidermal growth factors (EGF) previously reported were all in acidic solutions (pH 2.0-3.2), at which pHs EGF cannot bind to the receptor. Here we studied the structure of mouse EGF at pH 6.8, where EGF is physiologically active, and compared it with the structure at pH 2.0 by CD and NMR. From pH dependence of CD spectra and a comparison between the chemical shifts of the proton resonances at pH 6.8 and 2.0, the conformations at two pHs were found to be nearly identical except for the C-terminal tail region. The three-dimensional structures at pH 6.8 and 2.0 were determined independently by a combination of two-dimensional 1H NMR and stimulated annealing calculations using the program XPLOR. The calculations were based on 261 distance constraints at pH 6.8 and 355 distance and 24 torsion angle constraints at pH 2.0. The conformational difference of the C-terminal domain (residues 33-50) was detected between the two structures, which were supported by CD and the chemical shift comparison. The positions of the side chains of Leu47, Arg48, Trp49, and Trp50 are changed probably by the effect of the deprotonation of Asp46. Considering the fact that Leu47 is essential in EGF binding to the receptor, this conformational difference may be important in receptor recognition. PMID- 1445924 TI - Nonlocal structural perturbations in a mutant human insulin: sequential resonance assignment and 13C-isotope-aided 2D-NMR studies of [PheB24-->Gly]insulin with implications for receptor recognition. AB - Insulin's mechanism of receptor binding is not well understood despite extensive study by mutagenesis and X-ray crystallography. Of particular interest are "anomalous" analogues whose bioactivities are not readily rationalized by crystal structures. Here the structure and dynamics of one such analogue (GlyB24-insulin) are investigated by circular dichroism (CD) and isotope-aided 2D-NMR spectroscopy. The mutant insulin retains near-native receptor-binding affinity despite a nonconservative substitution (PheB24-->Gly) in the receptor-binding surface. Relative to native insulin, GlyB24-insulin exhibits reduced dimerization; the monomer (the active species) exhibits partial loss of ordered structure, as indicated by CD studies and motional narrowing of selected 1H-NMR resonance. 2D-NMR studies demonstrate that the B-chain beta-turn (residues B20 23) and beta-strand (residues B24-B28) are destabilized; essentially native alpha helical secondary structure (residues A3-A8, A13-A18, and B9-B19) is otherwise maintained. 13C-Isotope-edited NOESY studies demonstrate that long-range contacts observed between the B-chain beta-strand and the alpha-helical core in native insulin are absent in the mutant. Implications for the mechanism of insulin's interaction with its receptor are discussed. PMID- 1445925 TI - Proton NMR investigation of the oxidized three-iron clusters in the ferredoxins from the hyperthermophilic archae Pyrococcus furiosus and Thermococcus litoralis. AB - The 3Fe forms of ferredoxins (Fd) from the hyperthermophilic archaebacteria Pyrococcus furiosus (Pf) and Thermococcus litoralis (Tl) have been investigated by 1H NMR. A combination of one-dimensional nuclear Overhauser and two dimensional NOESY and bond correlation spectroscopy provides the assignment of the aromatic residues, one conserved valine, and the location of the signals for each of the three cysteines coordinated to the clusters. Dipolar contacts between the Trp 2 and Tyr 46 in Pf Fd and from an invariant phenylalanine to an invariant valine and a cluster cysteine in both Fd confirm a folding pattern for these proteins that is very similar to that of the crystallographically characterized ferredoxin from the mesophile Desulfovibro gigas. The sequence-specific assignment of the buried cysteine near the invariant phenylalanine has been made. The temperature dependence of the contact-shifted cysteinyl residues reveals a distinct 2:1 asymmetry in the magnetic coupling among the three high-spin ferric ions, in that one cysteine exhibits Curie behavior, while the other two cysteines display anti-Curie behavior. These magnetic properties are rationalized qualitatively on the basis of a magnetic coupling scheme where two iron couple to yield an intermediate spin of 2 which couples to the remaining S = 5/2 iron to yield the total cluster spin 1/2. This magnetic asymmetry appears to be a characteristic feature of oxidized 3 Fe clusters. Pf Fd also undergoes a dynamic equilibrium between two alternate forms that differ slightly in the environment of two of the coordinated cysteines. Analysis of the pattern of the contact shifts for the three cysteines in the two ferredoxins suggests that the cysteine coordinated to the unique iron does not have the same sequence origin. PMID- 1445926 TI - Glycine transformation of Ca2+ oscillations into a sustained increase parallels potentiation of insulin release. AB - Increase of the glucose concentration from 3 to 11 mM resulted in a triphasic release of insulin from perifused ob/ob-mouse beta-cells. A slight inhibition was followed after 2 min by a marked peak and a less pronounced sustained response. At the lower glucose concentration glycine had only marginal effects. However, in the presence of 11 mM glucose, 1-10 mM glycine triggered an immediate and dose dependent response with an initial peak of insulin release followed by sustained stimulation. In individual beta-cells, rise of the glucose concentration from 3 to 11 mM induced initial lowering of the cytoplasmic Ca2+ concentration ([Ca2+]i) followed by large amplitude oscillations from a level of 50-90 nM to peak values exceeding 300 nM. Already at a concentration of 1 mM, glycine transformed the oscillatory pattern into a sustained level with increase of time-average [Ca2+]i. This elevation became more pronounced in the presence of 10 mM glycine. The effects of glycine on insulin release and [Ca2+]i required extracellular Na+ and were reproduced with the N-methyl analogue sarcosine. It is suggested that glycine potentiation of secretion reflects the elevation of time-average [Ca2+]i both by increased entry and reduced elimination of the cation from the cytoplasm. PMID- 1445927 TI - Modulation of mitomycin C resistance by glutathione transferase inhibitor ethacrynic acid. AB - This study was undertaken to elucidate the mechanism(s) of cross-resistance (4.9 fold) to mitomycin C (MMC) in a multi-drug-resistant cell line, P388/R-84. Intracellular accumulation of MMC by sensitive (P388/S) and P388/R-84 cells was comparable. Despite a 32% reduction in NADPH cytochrome P-450 reductase activity (responsible for MMC activation) in P388/R-84 cells, the rate of MMC bio reduction by sensitive and resistant cells was similar. These results suggested that MMC resistance in P388/R-84 cell line must depend on factors other than impaired drug accumulation or bio-activation. Recent studies suggest that glutathione transferase (GST) dependent drug detoxification also contributes to cellular resistance of a variety of alkylating agents. Even though overexpression of GST has been noted in some MMC resistant tumor cells, it is not known if its level affects sensitivity to MMC. We have, therefore, determined the effect of ethacrynic acid (an inhibitor of GST activity) treatment on MMC cytotoxicity in P388/R-84 cells, which have about 2-fold higher GST activity than P388/S cells. The IC50 value for the inhibition of GST activity in vitro by ethacrynic acid (EA) was 16.5 microM (5 micrograms/ml). A depletion in intracellular GSH was also observed by treating P388/R-84 cells with EA alone or in combination with MMC. A non-toxic concentration of EA (1 microgram/ml; 3.3 microM) increased MMC cytotoxicity by 36% in P388/R-84 cells. MMC cytotoxicity was increased 2-fold by EA treatment in glutathione (GSH)-depleted P388/R-84 cells. These results suggest that GST mediated drug inactivation may represent another important mechanism of MMC resistance. PMID- 1445928 TI - The interaction of tetanus toxin with intact bovine adrenal chromaffin cells: binding of toxin and subsequent inhibition of catecholamine release. AB - Tetanus toxin (about 1 nM) inhibits 70% of the nicotine-evoked release of catecholamines from intact adrenal medullary chromaffin cells after 20 h of incubation and 30% of the K(+)-evoked release. Inhibition of Ca(2+)-evoked release from detergent-permeabilized cells requires higher concentrations of toxin (about 1 microM) toxin, but is maximal after 12 min. Preincubation of the intact cells with ganglioside GT1 in the absence of toxin also inhibits evoked secretion. 125I-labelled toxin bound specifically to these cells; the binding capacity was greater at pH 6 (about 1 pmol toxin/mg cell protein) than at pH 7.4 (about 0.25 pmol). In both cases there were at least two binding components: one of high affinity (Kd about 1 nM) accounting for about 20% of total binding and one of lower affinity (Kd 10-20 nM). Preincubation of the cells with ganglioside increased the binding capacity, but did not affect the Kd of the lower affinity component. Similar observations could be made when binding was measured immunocytochemically. Extraction of gangliosides from chromaffin cells and overlay experiments with radiolabelled toxin showed that, as well as GM3, the major ganglioside component of chromaffin cell membranes, a ganglioside having the chromatographic mobility of GT1 was a major ligand for toxin. PMID- 1445929 TI - Inhibition of platelet adhesion and thrombus formation on a collagen-coated surface by novel carbamoylpiperidine antiplatelet agents. AB - The inhibitory effect of two novel antiplatelet agents, 1,10-bis[3-(N,N diethylcarbamoyl)piperidino]decane dihydrobromide (G-110) and 1,6-bis[3-(N,N diethylcarbamoyl)piperidino]hexane dihydrobromide (G-112), on platelet adhesion and subsequent aggregation on collagen-coated surface was evaluated under controlled flow. Glass coverslips coated with bovine fibrillar collagen type I were exposed to heparinized human whole blood that had been preincubated with either aqueous solutions of one of the two carbamoylpiperidine congeners or corresponding amounts (1.0-4.0 microliters/ml blood) of distilled water, at a wall shear rate of 1000 s-1, in a parallel-plate perfusion chamber. Epifluorescence video microscopy with a microphotometric measurement technique was used to visualize and quantify deposition of fluorescently-labeled platelets from flowing whole blood onto the collagen-coated surface. At concentrations of 100 and 200 microM, G-110 inhibited platelet accumulation by 30 +/- 9% (+/- S.E.) and 63 +/- 3% (+/- S.E.), respectively; while G-112 reduced platelet deposition by 19 +/- 3% (+/- S.E.) and 31 +/- 2% (+/- S.E.) at concentrations of 200 and 400 microM, respectively. Digital image processing techniques were used to analyze the dynamics of thrombus growth on the collagen-coated surfaces. It was found that the compounds reduced the rate of thrombus growth by impeding both surface coverage and the number of platelets per thrombus in a concentration-dependent manner. This study, together with others on related compounds GT-12, BPAT-117 and BPAT-143, corroborates the nature of pivotal features in the molecular structure of carbamoylpiperidine and nipecotoylpiperazine derivatives which enhance desirable antithrombotic effects, e.g. intramolecular distance between two tertiary amines (ring nitrogens) and levels of hydrophobicity. PMID- 1445930 TI - Effects of cycloheximide, brefeldin A, suramin, heparin and primaquine on proteoglycan and glycosaminoglycan biosynthesis in human embryonic skin fibroblasts. AB - (1) We have isolated radiolabelled proteoglycans and glycosaminoglycans produced by human embryonic skin fibroblasts in the presence of (a) cycloheximide to inhibit protein synthesis or (b) brefeldin A to impede transport between the endoplasmic reticulum and the Golgi complex or (c) suramin, heparin or primaquine to interfere with internalization, recycling and degradation. Effects on glycosaminoglycan synthesis were assayed separately by using exogenous p nitrophenyl beta-D-xylopyranoside (and [3H]galactose) or 125I-labelled p hydroxyphenyl beta-D-xylopyranoside as initiators. (2) Inhibition of protein synthesis or blocking of transport to the Golgi complex prevented production of most of the proteoglycans with one exception: Cell-associated heparan sulphate proteoglycan was still produced at 20% of the control level. (3) Treatment with suramin or heparin resulted in decreased deposition of proteoglycan in the pericellular matrix but increased accumulation of cell-associated proteoglycan. Primaquine blocked all proteoglycan synthesis. (4) In the presence of cycloheximide, exogenous beta-D-xyloside initiated galactosaminoglycan production. In contrast, in brefeldin A-treated cells, synthesis was completely abolished. Not even formation of the linkage-region trisaccharide could be detected. (5) These results suggest that exogenous xyloside enters the endoplasmic reticulum and is subsequently transported to the trans-Golgi complex where all further steps involved in glycosaminoglycan assembly takes place. (6) Heparan sulphate proteoglycan produced by brefeldin A-treated cells could be derived from (a) an intracellular pool of preformed core protein located to the trans-Golgi complex, or (b) resident proteoglycan that was either deglycanated/reglycanated or chain-extended. As combined treatment with suramin and brefeldin A markedly reduced cell-associated proteoglycan production, the latter possibility is favoured. PMID- 1445931 TI - Nicotinic acetylcholine receptors of the central nervous system of Drosophila. PMID- 1445932 TI - Molecular dynamics of luteinizing hormone receptors on rat luteal cells. AB - To better understand the in situ organization of the luteinizing hormone receptor on rat luteal cells, we have examined the molecular motions of this receptor following binding of ovine luteinizing hormone (oLH) or human chorionic gonadotropin (hCG). Fluorescence photobleaching recovery (FPR) measurements of LH receptor lateral diffusion were performed using tetramethylrhodamine isothiocyanate (TRITC)-derivatized oLH or hCG as a probe. These experiments indicate that TRITC-oLH occupied LH receptors on luteal cells obtained from superovulated female rats have a lateral diffusion coefficient D of (1.7 +/- 0.6).10(-10) cm2s-1 at 27 degrees C with fluorescence recovery after photobleaching of 46 +/- 5%. In similar experiments, binding of TRITC-hCG caused a significant decrease in LH receptor lateral diffusion; fluorescence recovery after photobleaching was less than 20%. To determine whether hCG-occupied receptors might exist in large aggregates, we measured the rotational correlation times (RCT) of hCG and oLH bound to the LH receptor on intact cells using single cell polarized fluorescence depletion (PFD). At 4 degrees C, LH receptors occupied by eosin isothiocyanate (EITC)-hCG exhibited a slower RCT (64 microseconds) than did receptors occupied by EITC-oLH (43 microseconds). At this temperature both TRITC-oLH and TRITC-hCG occupied LH receptors were laterally immobile. These FPR and PFD results suggest that the molecular motions of the luteal cell LH receptor are significantly modulated by the subtle structural differences in various bound gonadotropins. PMID- 1445933 TI - trans-5-prostaglandin E2 stimulates plasminogen activation by tissue-type plasminogen activator. AB - The effect of trans-5-prostaglandin E2 (trans-PGE2) on fibrinolysis was examined in vitro using synthetic chromogenic substrate S-2251. trans-PGE2 was found to enhance plasminogen (PLG) activation mediated by tissue-type plasminogen activator (tPA). The enhancing effect was dependent on the concentration of trans PGE2. cis-PGE2 and the other PGs (PGE1 and PGI2) did not show such an effect as trans-PGE2, despite to the fact that their structures are similar to that of trans-PGE2. trans-Configuration around the double bond at the 5-position seems to be important in the enhancement of the fibrinolytic activity. PMID- 1445934 TI - Activators of protein kinase C decrease serotonin transport in human platelets. AB - Treatment of human platelets with activators of protein kinase C (PKC) for 5-20 min resulted in substantial reductions in the rate of platelet serotonin (5-HT) transport. The mean Vmax observed after 5 min treatment with 1 microM 4-beta-12 tetradecanoylphorbol 13-acetate (beta-TPA) was 66% (n = 16, P = 0.0001) of the control value. 5 min of treatment with 1 microM mezerein reduced uptake to 78% (n = 3, P = 0.01) of control. Both beta-TPA and mezerein had little effect on the Km of transport and had EC50 values of approx. 100 mM when a 20-min treatment period was used. The maximum effects of both were reached at approx. 20 min and could be blocked with staurospine. The beta-TPA effect was stereospecific, as alpha-TPA did not alter platelet 5-HT uptake. Although the PKC activators may have altered transmembrane ion-gradients for Na+ and Cl-, which are co-transported with 5-HT, minimizing ion-gradient changes had little effect on the observed reductions in transport. The PKC activators also had little or no effect on platelet 5-HT release or on the number (Bmax) of 5-HT transporters expressed at the platelet surface. The data indicate that PKC activation may down-regulate the activity of the 5-HT transporter in platelets. Apparently, most of this effect is mediated through mechanisms other than changes in ion-gradients, reductions in the number of available transporters, or increased 5-HT release. The apparent regulation of 5-HT transport by PKC may have important implications in platelet and neuronal functioning. PMID- 1445935 TI - Phytohormonal regulation of S-adenosylmethionine synthetase by gibberellic acid in wheat aleurones. AB - Gibberellic acid (GA3) brought about a 3-fold stimulation of AdoMet synthetase activity in wheat aleurones. At the qualitative level, three isozymes of AdoMet synthetase were observed by DE-52 chromatography in GA3-treated wheat aleurones. In contrast, the control wheat aleurones showed a single isozyme. Thus the phytohormone (GA3, 1 microM) induced two additional isozymes of AdoMet synthetase in wheat aleurones. The activity of all the three isozymes in GA3-treated aleurones was considerably decreased by the simultaneous presence of abscisic acid (ABA, 10 microM). Cycloheximide (20 micrograms/ml) also significantly lowered the levels of the three isozymes of AdoMet synthetase in Ga3-treated aleurones, thereby suggesting the requirement of de-novo protein synthesis for the complete induction of isozymes. However, wheat aleurones excised from embryonated wheat seeds, did not require the application of GA3 for the induction of two additional isozymes of AdoMet synthetase. Apparently, the transport of GA3 from the embryo to aleurones induced two new isozymes of AdoMet synthetase. Three isozymes of AdoMet synthetase were also observed in wheat embryos excised from germinated wheat grains, without exogenous application of GA3. The molecular weight of all the three isozymes of AdoMet synthetase in wheat system is 181,000. The molecular weight of the subunit of the enzyme is 84,000. The dimeric nature of AdoMet synthetase was established by SDS-PAGE analysis of the purified enzyme. In-vitro hybridization of two flanking isozymic peaks I and III by NaCl-freeze thaw method resulted in the appearance of an additional middle activity peak (isozyme II). However, no additional isozymic peaks were generated when isozymic peaks I and III were individually given a freeze-thaw treatment. Thus the flanking isozymic peaks I and III represent homodimers that differed in their net charge. In contrast, the middle isozymic activity peak II, when subjected to NaCl freeze-thaw treatments yielded two additional isozymic peaks, I and III, thereby suggesting its heterodimeric nature. We envisage that the three isozymes in GA3 treated wheat aleurone layers are formed by the random dimerization of two classes of enzyme subunits. The two enzyme subunits which differ in their net charge could be the product of two genes of AdoMet synthetase (SAM1 and SAM2). Based on this assumption, we propose that a single isozyme I in water imbibed control wheat aleurones is the product of SAM1 gene of AdoMet synthetase. The occurrence of three isozymes in GA3-treated aleurones could be ascribed to the expression of an alternate gene of AdoMet synthetase (SAM2 gene).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1445936 TI - Conservation of sequences of subunits of mitochondrial complex I and their relationships with other proteins. PMID- 1445937 TI - Thermoluminescence and flash-induced oxygen yield in herbicide resistant mutants of the D1 protein in Synechococcus PCC7942. AB - Several strains of Synechococcus PCC7942 carrying point mutations in the gene psbA were studied by thermoluminescence and polarographic measurement of flash induced oxygen yield. The following results were obtained: (a) Replacement of Ser 264 in D1 by Ala (mutant Di1) or Gly (mutant G264) resulting in DCMU and atrazine resistance leads to a downshift of the thermoluminescence (TL) B-band peak temperature from 40 degrees C in wild-type thylakoids to about 30 degrees C. In dark adapted samples of both mutants the TL and oxygen yield pattern induced by a train of single turnover flashes were strongly damped indicative of a high miss factor. (b) In contrast to Ser-264 mutants, replacement of Phe-255 in D1 by Tyr (mutant Tyr5) induced strong resistance to atrazine but not to DCMU and did not affect the peak termperature of the B-band and the flash-induced TL and oxygen yield patterns. In this respect mutant Tyr5 resembles the wild type. (c) No significant differences have been found between strains with single site mutations in psbAI and normal psbAII/psbAIII genes, and strains with same mutations in psbAI but additional deletion of psbAII and psbAIII. Obviously in strains were psbAI is present, PS II complexes containing gene products of psbAII and psbAIII are not assembled in detectable amounts. (d) Strains with double mutations at positions 264 and 255 display a downshift of the B-band peak temperature. Their oscillatory patterns of B-band intensity and oxygen yield are highly damped. This behaviour is similar to strains D1 and G264 which are modified at position 264 only. We extend reports on additivity of mutation effects on herbicide binding to binding of QB. (e) Mutations at the QB site not only influence the binding of QB and herbicides but also change the thermoluminescence quantum yield and the lifetimes of the redox states S2 and S3 of the water oxidase. This finding might indicate long ranging effects on Photosystem II exerted by structural modifications of the QB site. From these data we conclude that Ser-264 is essential for binding of atrazine, DCMU and QB, whereas Phe-255 is involved in atrazine binding and its substitution by Tyr does not markedly affect QB or DCMU binding in Synechococcus PCC7942. PMID- 1445938 TI - Added subunit beta of CF1 as well as gamma/delta/epsilon restore photophosphorylation in partially CF1-depleted thylakoids. AB - We investigated the ability of subunits beta, gamma, delta, and epsilon of CF1, the F1-ATPase of chloroplasts, to interact with exposed CF0 in EDTA-treated, partially CF1-depleted thylakoid membranes. We measured the ability of subunits beta, gamma, delta, and epsilon to stimulate the rate of photophosphorylation under continuous light and, for subunit beta, also the ability to diminish the proton leakage through exposed CF0 by deceleration of the decay of electrochromic absorption transients under flashing light. The greatest effect was caused by subunit beta, followed by gamma/delta/epsilon. Pairwise combinations of gamma, delta, and epsilon or each of these subunits alone were only marginally effective. Subunit gamma from the thermophilic bacterium PS 3 in combination with chloroplast delta and epsilon was as effective as chloroplast gamma. The finding that the small CF1 subunits in concert and the beta subunit by itself specifically interacted with the exposed proton channel CF0, qualifies the previous concept of subunit delta acting particularly as a plug to the open CF0 channel. The interactions between the channel and the catalytic portion of the enzyme seem to involve most of the small, and at least beta of the large subunits. PMID- 1445939 TI - The effect of delta mu H+ on the interaction of rotenone with complex I of submitochondrial particles. AB - The inhibition by rotenone of the forward (NADH-oxidase) and reverse (delta mu H(+)-dependent succinate-NAD+ reductase activities of submitochondrial vesicles was measured. The inhibition of NADH-oxidase, measured in the presence of uncoupler, followed a monophasic inhibition curve with Ki < or = 2 nM. The reverse electron flow was only partially (40%) inhibited at these rotenone concentrations. The rest of the activity was less sensitive to the inhibitor (Ki approximately 30 nM). The lower affinity for the inhibitor of the reverse electron flow is a consequence of enhanced rate of rotenone dissociation caused by the high delta mu H+ value required for this reaction. The analysis of the results indicates that the AS-SMP preparation consists of two subpopulations: one with a relatively low degree of coupling, which exhibits high sensitivity to rotenone and the other which is highly coupled with lower affinity to the inhibitor. PMID- 1445940 TI - Prediction of transmembrane topology of F0 proteins from Escherichia coli F1F0 ATP synthase using variational and hydrophobic moment analyses. AB - The a subunit, a membrane protein from the E. coli F1F0 ATP synthase has been examined by Fourier analysis of hydrophobicity and of amino-acid residue variation. The amino-acid sequences of homologous subunits from Vibrio alginolyticus, Saccharomyces cerevisiae, Neurospora crassa, Aspergillus nidulans, Schizosaccharomyces pombe and Candida parapsilosis were used in the variability analysis. By Fourier analysis of sequence variation, two transmembrane helices are predicted to have one face in contact with membrane lipids, while the other spans are predicted to be more shielded from the lipids by protein. By Fourier analysis of hydrophobicity, six amphipathic alpha-helical segments are predicted in extra-membrane regions, including the region from Glu-196 to Asn-214. Fourier analysis of sequence variation in the b- and the c-subunits of the Escherichia coli F1F0 ATP synthase indicates that the single transmembrane span of the b subunit and the C-terminal span of the c subunit each have a face in contact with membrane lipids. On the basis of this analysis topographical models for the a- and c-subunits and for the F0 complex are proposed. PMID- 1445941 TI - Microtubule organization by cross-linking and bundling proteins. AB - To understand microtubule function the factors regulating their spatial organization and their interaction with cellular organelles, including other microtubules, must be elucidated. Many proteins are implicated in these organizational events and the known consequences of their actions within the cell are increasing. For example, the function of microtubule bundles at the surfaces of polarized cells has recently received attention, as has the action in cortical rotation of a transient arrangement of microtubules found beneath the vegetal surface of fertilized frog eggs. The in vivo association of microtubules during early Xenopus oogenesis has added interest as microtubules bundled in cell-free extracts are protected against the action of a severing protein found in this animal. A 52 kDa F-actin bundling protein purified from Physarum polycephalum organizes microtubules and causes the cobundling of microtubules and microfilaments. These observations, in concert with others that are presented, emphasize the diversity within the family of microtubule cross-linking proteins. The challenge is to determine which proteins are relevant from a physiological perspective, to ascertain their molecular mechanisms of action and to describe how they affect cytoplasmic organization and cell function. To realize this objective, the proteins which cross-link and bundle microtubules must be investigated by techniques which reveal different but related aspects of their properties. Cloning and sequencing of genes for cross-linking proteins, their subcellular localization especially as microtubule-related changes in cell morphology are occurring and the application of genetic studies are necessary. Study of the neural MAP provides the best example of just how powerful current experimental approaches are and at the same time shows their limits. The neural MAP have long been noted for their enhancement of tubulin assembly and microtubule stability. Their spatial distribution has been studied during the morphogenesis of neural cells. Sequencing of cloned genes has revealed the functional domains of neural MAP including carboxy-terminal microtubule-binding sites. Similarities to microtubule binding proteins from other cell types stimulate interest in the neural MAP and further suggest their importance in microtubule organization. For example, MAP4 enjoys a wide cellular distribution and has microtubule-binding sequences very similar to those in the neural MAP. Moreover, the nontubulin proteins of marginal bands are immunologically related to neural MAP, indicating shared structural/functional domains. Even with these findings the mechanism by which neural MAP cross-link microtubules remains uncertain. Indeed, some researchers express doubt that microtubule cross-linking is actually a function of neural MAP in vivo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1445943 TI - Purine nucleoside phosphorylase from bovine lens: purification and properties. AB - Purine nucleoside phosphorylase (purine nucleoside: orthophosphate ribosyltransferase, EC 2.4.2.1) was purified 38,750-fold to apparent electrophoretic homogeneity from bovine ocular lens. The enzyme appears to be a homotrimer with a molecular weight of 97,000, and displays non-linear kinetics with concave downward curvature in double-reciprocal plots with orthophosphate as variable substrate. The analysis of the kinetic parameters of bovine lens purine nucleoside phosphorylase, determined both for the phosphorolytic activity on nucleosides and for ribosylating activity on purine bases, indicates the occurrence of a rapid equilibrium random Bi-Bi mechanism with formation of abortive complexes. The effect of pH on the enzyme activity and on the sensitivity of the enzyme to photoinactivation, as well as the effect of thiol reagents on the enzyme activity and stability, strongly suggest the involvement of histidine and cysteine residues in the active site. From the measurements of the kinetic parameters at different temperatures, heats of formation of the enzyme-substrate complex for guanosine, guanine, orthophosphate and ribose 1 phosphate were determined. Activation energies of 15,250 and 14,650 cal/mol were obtained for phosphorolysis and synthesis of guanosine, respectively. PMID- 1445942 TI - Multinuclear NMR studies of the trp-repressor. AB - The binding of the corepressor, L-tryptophan, to the Escherichia coli trp aporepressor in solution has been examined by 13C- and 19F-NMR spectroscopy. The binding of a number of tryptophan analogues have been studied by equilibrium dialysis. Evidence is presented that support the crystallographic studies (Schevitz, R. W., Otwinowski, Z., Joachimiak, A., Lawson, C. L. and Sigler, P. B. (1985) Nature 317, 782-786) that Val-58 is within the ring currents of the bound tryptophan and also close in space to the indole 5'-position, on the basis of heteronuclear 19F(1H)-NOE experiments. The tryptophan carboxylate is in hydrogen bonding distance to a highly positively charged residue, probably Arg-54 and this bond strengthens on formation of the trp-repressor-DNA complex. PMID- 1445944 TI - An immunochemical assay model system for the sensitive detection of pyruvate dehydrogenase complex (PDHc) and its decarboxylating subunit pyruvate dehydrogenase (E1). AB - An immunochemical enzyme immunoassay model system was developed and compared for maximum sensitivity with a radioimmunoassay method and the classic enzyme activity method for the detection of pyruvate dehydrogenase complex (PDHc) and its decarboxylating subunit, pyruvate dehydrogenase (E1), isolated from Escherichia coli. Cross-linked large molecular weight antibody-enzyme conjugate systems are compared with heterobifunctional singular antibody conjugates substituted with high levels of horseradish peroxidase. Both polyclonal and monoclonal antibodies generated to the Escherichia coli PDHc and E1 antigens were used to develop a double-antibody sandwich microtiter plate enzyme-linked immunosorbent assay. It is demonstrated that a double sandwich immunochemical assay system can be quantitative for PDHc, can detect PDHc in crude cell lysates and has levels of sensitivity of 2.0.10(-16) mol for the detection of PDHc. This assay model system provides specific antibody selection criteria and coupling methods needed to select specific antisera that cross-react with human PDHc. This rapid and sensitive immunochemical assay method clearly demonstrates that sensitive mass assay systems can be developed for the detection of PDHc. Different from Western blot, this methodology could be used to generate mass assays which could be applied to the rapid detection of mammalian antigens (employing the corresponding antibodies) implicated in a number of pyruvate dehydrogenase deficiencies associated with human disorders. PMID- 1445945 TI - Nucleophile specificity in alpha-chymotrypsin- and subtilisin-(Bacillus subtilis strain 72) catalyzed reactions. AB - Nucleophilic properties of amino-acid amides were studied systematically in acyl transfer reactions catalyzed by alpha-chymotrypsin and subtilisin from Bacillus subtilis strain 72 (subtilisin 72) using Mal-L-Ala-L-Ala-L-PheOMe as the acyl group donor. In alpha-chymotrypsin-catalyzed reactions, the nucleophile reactivities increase in the following order: D-AlaNH2 < GlyNH2 < L-AlaNH2 < L SerNH2 < L-ThrNH2 < L-HisNH2 < L-ValNH2 < L-LeuNH2 < L-TrpNH2 < L-MetNH2 < L NvaNH2 < L-PheNH2 < L-IleNH2 < L-TyrNH2 < L-ArgNH2. In reactions catalyzed by subtilisin 72, the reactivities increase as follows: L-LeuNH2 < L-IleNH2 < L ThrNH2 < L-ArgNH2 < L-TrpNH2 < L-NvaNH2 < L-ValNH2 < L-MetNH2 < L-AlaNH2 < L SerNH2 < D-AlaNH2 < GlyNH2. In alpha-chymotrypsin-catalyzed reactions, hydrophobic interactions are entirely responsible for the differences between the reactivity of the nucleophiles for amides of all the amino-acids tested with the exception of D-AlaNH2, L-ArgNH2 and L-TyrNH2. In reactions catalyzed by subtilisin 72, amino-acid side-chain characteristics and the nucleophile reactivities are not related. The data obtained show the low selectivity of the S1' subsite of subtilisin 72 and high specificity of this subsite in alpha chymotrypsin. PMID- 1445946 TI - Purification and characterization of a low M(r) GTP-binding protein, c25KG, from human platelet membranes. AB - A low M(r) GTP-binding protein with a M(r) of 26,000 has been purified from a sodium cholate extract of human platelet membranes by using an antibody raised against a synthetic peptide of c25KG, which was previously purified from human platelet cytosol (Nagata, N., et al. (1989) J. Biol. Chem. 264, 17000-17005). The M(r) of membranous c25KG (m-c25KG) was slightly higher than that from cytosolic c25KG (M(r) 25,000) and calculated to be 26,000. It was suggested that m-c25KG contains an equimolar amount of GDP. The purified protein could bind approx. 1 mol of [35S]guanosine 5'-O-(thiotriphosphate)(GTP gamma S)/mol of protein, with a Kd value of 50 nM. [35S]GTP gamma S-binding to this protein was inhibited by GTP and GDP, but not by ATP and ADP, showing that the binding is specific for guanine. In the presence of 10 mM Mg2+, the dissociation of [8,5'-3H]GDP from the m-c25KG occurred with a rate of 0.01 min-1. The rate of release of Pi from [gamma 32P]GTP-bound m-c25KG was calculated to be 0.03 min-1. These results indicate that c25KG is also present in membrane fraction of human platelet which has very similar biochemical properties in those of the cytosolic type. PMID- 1445947 TI - Expression of a hyperthermophilic aspartate aminotransferase in Escherichia coli. AB - The gene for an archaebacterial hyperthermophilic enzyme, aspartate aminotransferase from Sulfolobus solfataricus (AspATSs), was expressed in Escherichia coli and the enzyme purified to homogeneity. A suitable expression vector and host strain were selected and culture conditions were optimized so that 6-7 mg of pure enzyme per litre of culture were obtained repeatedly. The recombinant enzyme and the authentic AspATSs are indistinguishable: in fact, they have the same molecular weight, estimated by means of SDS-PAGE and gel filtration, the same Km values for 2-oxo-glutarate and cysteine sulphinate and the same UV-visible spectra. Moreover, recombinant AspATSs is thermophilic and thermostable just as the enzyme extracted from Sulfolobus solfataricus. The protocol described may be used to produce thermostable arachaebacterial enzymes in mesophilic hosts. PMID- 1445948 TI - Plant cytosolic pyruvate kinase: a kinetic study. AB - The kinetic properties of cytosolic pyruvate kinase (PKc) from germinating castor oil seeds (COS) have been investigated. From experiments in which the free Mg2+ concentration was varied at constant levels of either the complexed or free forms of the substrates it was determined that the true substrates are the free forms of both phosphoenolpyruvate (PEP) and ADP. This conclusion is corroborated by the quenching of intrinsic PKC tryptophan fluorescence by free PEP and ADP. Mg2+ is bound as the free bivalent cation but is likely released as MgATP. The fluorescence data, substrate interaction kinetics, and pattern of inhibition by products and substrate analogues (adenosine 5'-O-(2-thiodiphosphate) for ADP and phenyl phosphate for PEP) are compatible with a sequential, compulsory-ordered, Tri-Bi type kinetic reaction mechanism. PEP is the leading substrate, and pyruvate the last product to abandon the enzyme. The dissociation constant and limiting Km for free PEP (8.2 to 22 and 38 microM, respectively) and the limiting Km for free ADP (2.9 microM) are considerably lower than those reported for the non-plant enzyme. The results indicate that COS PKc exists naturally in an activated state, similar to the fructose 1,6-bisphosphate-activated yeast enzyme. This deduction is consistent with a previous study (F.E. Podesta and W.C. Plaxton (1991) Biochem. J. 279, 495-501) that failed to identify any allosteric activators for the COS PKc, but which proposed a regulatory mechanism based upon ATP levels and pH-dependent alterations in the enzyme's response to various metabolite inhibitors. As plant phosphofructokinases display potent inhibition by PEP, the overall rate of glycolytic flux from hexose 6-phosphate to pyruvate in the plant cytosol will ultimately depend upon variations in PEP levels brought about by the regulation of PKc. PMID- 1445949 TI - Catalytic oxidation of 2,4,5-trihydroxyphenylalanine by tyrosinase: identification and evolution of intermediates. AB - The oxidation of 3,4-dihydroxyphenylalanine (dopa) by O2 catalyzed by tyrosinase yields 4-(2-carboxy-2-aminoethyl)-1,2-benzoquinone, with its amino group protonated (o-dopaquinone-H+). This evolves non-enzymatically through two branches (cyclization and/or hydroxylation), whose respective operations are determined by pH. The hydroxylation branch of o-dopaquinone-H+ only operates significantly at pH < or = 5.0 and involves the accumulation of 2,4,5 trihydroxyphenylalanine (topa), which has been detected by high-performance liquid chromatography (HPLC). This last compound is also a substrate of tyrosinase. The oxidation of topa by both tyrosinase and periodate yields 5-(2 carboxy-2-aminoethyl)-4-hydroxy-1,2-benzoquinone, with its amino group protonated (o-topaquinone-H+), which is red (RTQH) (lambda max 272-485 nm) at pH 7.0 and yellow (TTQH) (lambda max 265-390 nm) at pH 3.0. This is based on pKa 4.5 of the 2-OH group of the benzene ring of o-topaquinone-H+, as derived from spectrophotometric and HPLC assays. At physiological pH, RTQH undergoes deprotonation of the ammonium group of the side chain to yields RTQ, which cyclize into 2-carboxy-2,3-dihydroxyindolen-5,6-quinone (dopachrome), with a 1:1 stoichiometry and first-order kinetics. The evolution of RTQH has been analyzed by spectrophotometry, HPLC, cyclic voltammetry and constant potential electrolytic assays. From HPLC assays, the value of the first-order constant for the evolution of RTQH at pH 7.0 (kRTQHapp 4.83 x 10(-5) s-1), as well as of the rate constant for the cyclization step of RTQ (kRTQc 2.53 x 10(-3) s-1) were determined. PMID- 1445950 TI - Glycyrrhetinic acid bound to 11 beta-hydroxysteroid dehydrogenase in rat liver microsomes. AB - A binding protein which exhibits high affinity to [3H]glycyrrhetinic-acid in the rat liver microsomal fraction was solubilized with 0.2% Triton DF-18 and then purified to homogeneity. The equilibrium dissociation constant of the [3H]glycyrrhetinic-acid binding reaction and the maximal concentration for the binding of the purified protein, as determined by Scatchard plot analysis, were 27.6 nM and 7.79 nmol/mg protein, respectively. The molecular mass of the subunit (34 kDa) and 30 amino acids of N-terminal sequence of the purified protein were entirely the same as those of the reported 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). In each purification step, the recovery and purification (fold) of the glycyrrhetinic-acid binding activity corresponded to the values of 11 beta HSD activity. These results show that the purified [3H]glycyrrhetinic-acid binding protein is 11 beta-HSD. From the molecular mass of 11 beta-HSD (135 kDa) and the maximal concentration of the binding site, it was calculated that one glycyrrhetinic acid molecule binds to one 11 beta-HSD molecule. The inhibitory effects of various glycyrrhetinic-acid derivatives on [3H]glycyrrhetinic acid binding and 11 beta-HSD activity indicate that the C30-carboxyl and C11-carbonyl groups of glycyrrhetinic acid are the principal structures for the 11 beta-HSD inhibition. PMID- 1445951 TI - A 1H-NMR study of the interactions between rat tissue kallikrein and two peptide inhibitors. AB - The 1H-NMR spectra have been obtained for rat submandibular kallikrein in the absence and presence of inhibitors. Two competitive inhibitors were investigated, the tripeptide leupeptin (a potent inhibitor with Ki 0.5 microM) and a hexapeptide (a much weaker, substrate-analogue inhibitor with Ki 380 microM). Analysis of the NMR spectra showed that binding of leupeptin to kallikrein led to a change in the conformation of the enzyme, whereas binding of the substrate analogue to the enzyme produced no such change and may have resulted in a conformational change of the inhibitor. PMID- 1445952 TI - What methods of pediatric pain management can be incorporated into a generalist's anesthesia practice? AB - Historically, pain in ill and injured pediatric patients has not been recognized or attended to. Subsequently, children often suffer in silence. Caretakers are often fearful to intervene aggressively to alleviate pain. A critical evaluation and integrative approach to the treatment of pediatric pain has only recently emerged, and curricula addressing the physiologic, behavioral, and biochemical differences related to pain has only recently been instituted in some medical schools and pediatric training programs. Children deserve special consideration in pain management since they may not be capable of comprehending the need for painful procedures and may not have learned strategies to cope with them. The importance of a comprehensive evaluation can not be overstated. The anesthetist can be of great assistance in pain management of the pediatric surgical patient by assessing his patient's postoperative pain needs and planning his/her anesthetic technique and recovery room course accordingly. Research in pediatric pain is still in its infancy, with crucial issues yet to be addressed. One of the most important is how to individualize the treatment of pain. We also need to learn more about children's natural coping styles and how parents and health care providers can enhance their effectiveness in contributing to the therapeutic team. It is hoped that readers will notice their patient's behaviors a little more closely, think about the extent of their private suffering, and become willing to offer a more studied, justifiable, and aggressive approach to pediatric pain management. PMID- 1445953 TI - A study of six common neuroanesthesia cases. AB - Certified Registered Nurse Anesthetists (CRNAs) provide anesthesia to a wide spectrum of patients, including those undergoing various neurosurgical procedures. While some CRNAs specialize in neuroanesthesia, most are involved on a more episodic basis. Using a case study format, this article reviews the pathophysiology associated with six common neurologic conditions the general practice CRNA may encounter. Important anesthesia considerations for each condition are discussed. PMID- 1445954 TI - Central anticholinergic syndrome in a pediatric patient following transdermal scopolamine patch placement. AB - A 9-year-old child was admitted to the hospital with congenital left ureteropelvic junction obstruction with massive left pyelocaliectasis and underwent dismembered pyeloplasty of the left kidney under general anesthesia without complications. Postoperatively, the child was placed on patient controlled analgesia, with morphine as the drug of choice. The patient was discharged to the ward with adequate pain control and no complaints of nausea or vomiting. Once on the ward, a transdermal scopolamine patch was placed for nausea and vomiting. More than 24 hours after patch placement, the child experienced central anticholinergic syndrome (CAS) with hallucinations and incontinence. The scopolamine patch was promptly removed, and all symptoms of CAS rapidly ceased. A transdermal scopolamine patch should not be used in the pediatric population, and with extreme caution in the elderly. Treatment of CAS includes prompt removal of the patch, cleansing of the area, and possible physostigmine administration. PMID- 1445955 TI - Ketorolac as a preoperative nonnarcotic analgesic to enhance anesthesia and postanesthesia recovery. AB - The benefits of using ketorolac as a preoperative intramuscular (IM) non-narcotic analgesic are described and illustrated by the presentation of two case reports. Case Summary--Patient 1: A 53-year-old female who had experienced refractory nausea and vomiting after six previous exposures to anesthesia presented for outpatient ureteroscopy and dilatation of strictures. Instead of using an opiate narcotic, ketorolac 60 mg IM was given 1 hour before induction as the analgesic portion of anesthesia. Case Summary--Patient 2: A 65-year-old male with mild chronic obstructive lung disease presented for extracorporeal shock wave lithotripsy (ESWL). To avoid the respiratory depression associated with opioid narcotics, ketorolac 60 mg IM was given as an analgesic 1 hour before the ESWL procedure. PMID- 1445957 TI - Representation by organized labor unions may no longer be an effective solution to providing employment security to CRNAs in the 1990s. PMID- 1445956 TI - Professional wake-up call: health care reform legislation. PMID- 1445958 TI - Changed purine nucleotide concentrations and enzyme activities in erythrocytes of haemodialysis patients undergoing erythropoietin therapy. AB - Therapy of renal anaemia in haemodialysis patients with chronic renal failure by application of recombinant human erythropoietin leads to an increase of the haematocrit. Rejuvenation of the erythrocyte population results in a decrease of the median density (D50), an increase of cell age-dependent enzyme activities, such as aspartate aminotransferase, and elevated concentrations of purine nucleotides in the erythrocytes. After density gradient separation of erythrocyte populations into cell age-dependent fractions, the concentrations of adenosine-5' triphosphate, guanosine-5'-triphosphate and guanosine-5'-diphosphate were be found to be elevated by 25-100% in all cell fractions from haemodialysis patients, compared with a healthy control group. Therapy of haemodialysis patients with recombinant human erythropoietin leads to further increase (65%) of ATP in the younger (low density) cells, but not in the older (high density) cells. The elevated concentrations of ATP and total adenine nucleotides during recombinant human erythropoietin therapy possibly result in improved deformability of erythrocytes. The data point to an enhancement of the proportion of younger erythrocytes, but not to an improvement of the reduced life span of erythrocytes of haemodialysis patients during therapy with recombinant human erythropoietin. PMID- 1445959 TI - Comparison of markers of coagulation activation in patients under oral anticoagulation at different levels. AB - Three groups of patients receiving oral anticoagulation treatment were evaluated. The groups consisted of patients with mechanical heart valve prosthesis (n = 60), patients after coronary bypass graft surgery (n = 60) and patients using oral anticoagulation after deep venous thrombosis or pulmonary embolism (n = 60). The patient groups were subdivided into three groups of 20 patients, each group receiving different levels of oral anticoagulation as indicated by the international normalized ratio (INR). Prothrombin fragment 1 + 2, thrombin antithrombin III complexes and fibrin monomers were determined as coagulation activation makers. The prothrombin fragments 1 + 2 were INR dependent in all groups whereas the thrombin-antithrombin III values were only INR dependent in the group of patients with mechanical heart valve prosthesis. For fibrin monomers no correlation with the INR levels could be found. These results indicate that prothrombin fragment 1 + 2 is the only laboratory quantity of the three, which provides a suitable index of low thrombin activity during anticoagulation therapy. PMID- 1445960 TI - Coagulation and fibrinolysis markers in seminal plasma of patients under evaluation for involuntary childlessness. AB - Semen specimens from four groups of patients were evaluated for coagulation and fibrinolysis factors: a group of patients with infertile semen and involuntary childlessness (n = 35), a group with fertile semen and involuntary childlessness (n = 39), a group with fertile semen and proven fertility before vasectomy (n = 34) and a group with infertile semen after vasectomy (n = 147). The third patient group with proven fertility before vasectomy was considered as a control group. Only small amounts of fibrinogen, factor VIII:c, plasminogen, antithrombin III, fibrin monomers and plasminogen activator inhibitor-1 were detected in seminal plasma. The thrombin-antithrombin III, D-dimer and tissue plasminogen activator regular concentrations were measured and the D-dimer/thrombin-antithrombin III ratios calculated. The reference ranges were assessed and the quantities were compared in the different patient groups. Significant differences were demonstrated between the prevasectomy group (= control group) and both the postvasectomy and the infertility groups with respect to D-dimer and D dimer/thrombin-antithrombin III ratio. We conclude that both coagulation and fibrinolysis play a part in coagulum formation and liquefaction of seminal plasma. The balance between coagulation and fibrinolysis (expressed as D dimer/thrombin-antithrombin III ratio) was significantly different between the control group and the three patient groups. The coagulation/fibrinolysis balance was impaired in the semen from post vasectomy patients and from those with involuntary childlessness and the D-dimer/thrombin-antithrombin III ratios in both these patient groups were very similar. PMID- 1445961 TI - Structural and functional characterization of plasma fibronectin in patients with essential mixed cryoglobulinaemia. AB - Experimental studies suggest that plasma fibronectin may be involved in the cryoprecipitation of cryoglobulins in essential mixed cryoglobulinaemia; reduced plasma concentrations of the glycoprotein have been shown in the disease. The present work was undertaken in order to verify this latter finding and to detect a possible structural alteration of plasma fibronectin as result of enzymatic digestion of the molecule in vivo. This could, in turn, induce a decreased reactivity of the protein in immunometric assays and a reduced opsonic activity, which is normally due to the affinity of fibronectin to the C1q component of complement. Moreover, since a polymorphic variant of fibronectin has been described in plasma during experimental vascular injury and in patients with autoimmune vascular diseases, the aim of this study was also to verify the presence of a polymorphism of the glycoprotein in cryoglobulinaemic vasculitis. Twenty seven patients with essential mixed cryoglobulinaemia and 26 normal subjects were included in the study. Significantly reduced concentrations of plasma fibronectin, as assessed by ELISA, were found in patients when compared with controls (231.7 +/- 15.3 vs 316.1 +/- 16.6 mg/l, P less than 0.0002). In contrast, when affinity-purified plasma fibronectin from 10 patients with essential mixed cryoglobulinaemia and 8 healthy subjects were analysed by western blotting, employing a panel of five monoclonal antibodies to different regions of the molecule, no differences were observed between patients and controls, suggesting integrity of the glycoprotein in the disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1445962 TI - Enzymes of the pentose phosphate pathway in glutathione-regulated membrane protection in beta-thalassaemia. AB - The mass concentrations of whole blood reduced glutathione and catalytic activity concentrations of the enzymes, glucose-6-phosphate dehydrogenase (EC 1.1.1.49), glutathione reductase (EC 1.6.4.2) and glutathione peroxidase (EC 1.11.9) were analysed in 25 cases of homozygous beta-thalassaemia, 20 cases of heterozygous beta-thalassaemia and 10 controls. The results showed a significant elevation of reduced glutathione and enzymes of the pentose phosphate pathway in homozygous beta-thalassaemia, indicating the existence of an enzyme-regulated glutathione turnover system in the overt state to combat the augmented red cell membrane damage due to auto-oxidant threat. However, in heterozygous beta-thalassaemia, reduced glutathione was increased, but there was no similar elevation of enzymes except for glutathione peroxidase. PMID- 1445963 TI - Multicentre evaluation of a two-step automated enzyme immunoassay of free thyroxine. AB - The two-step enzymatic immunoassay of free thyroxine (IMx FT4, Abbott Laboratories, Chicago, IL) was studied in three centres. The assay involved a fluorimetric measurement and took 45 minutes using a completely automated procedure. The results were compared with those from the free thyroxine two-step radioimmunoassay and with the "calculation" of free thyroxine. The analytical precision was found to be excellent if the analyser was correctly set. The IMx FT4 assay seemed unaffected by increased concentrations of albumin and of non esterified fatty acids (oleic acid) up to 5 mmol/l. The euthyroid reference interval, defined as that including 95% of 194 control subjects, was 12-21 pmol/l. A limited overlap existed between euthyroid and hyperthyroid patients, but a larger one was seen between the euthyroid and hypothyroid population, the latter including subclinical hypothyroidism. IMx FT4 results agreed well when compared with those from two-step radioimmunoassays. The IMx FT4 technique gave rise to a low percentage of elevated results in patients being treated with heparin, but was undisturbed by autoantibodies to thyroxine and triiodothyronine which were present in one hypothyroid patient. PMID- 1445964 TI - Proposal of standard methods for the determination of enzyme catalytic concentrations in serum and plasma at 37 degrees C. III. Glutamate dehydrogenase (L-glutamate: NAD(P)+ oxidoreductase (deaminating), EC 1.4.1.3). Working Group on Enzymes. PMID- 1445965 TI - Ziskind-Somerfeld Research Award 1992. Endogenous biochemical abnormalities in affective illness: therapeutic versus pathogenic. AB - Examination of the neurobiology of psychiatric illness in general, and of affective disorders in particular, reveals a variety of associated biochemical abnormalities. These have generally been assumed to be part of the pathological process or secondary to it, and thus deserving of therapeutic efforts aimed at reversal. However, recent clinical and preclinical data suggest that some alterations occurring in the affective disorders may be compensatory and adaptive; that is, part of an endogenous therapeutic mechanism rather than part of the evolving disease process. For example, the symptom of sleep loss in depression seems to fall under this rubric inasmuch as sleep deprivation induces mood improvement in depressed patients. Preclinical data are presented that another primary pathological process--the occurrence of kindled seizures--can evoke endogenous compensatory processes that are either anticonvulsant in their own right, or enable the anticonvulsant effects of a drug such as carbamazepine. It may be that some biochemical abnormalities occurring in affective illness are similarly adaptive. As one example, increased thyrotropin-releasing hormone (TRH) has been reported in the cerebrospinal fluid (CSF) of depressed patients. This elevation of TRH and the resulting neuroendocrine profile may be part of an endogenous counter-regulatory process aimed at mood improvement. Again, preclinical seizure models are supportive in that TRH not only is induced following repeated seizures, but also exerts anticonvulsant effects on these same seizures. In an analogous fashion, TRH elevations in depressed patients may also exert ameliorating effects on depressive symptomatology. This formulation presents directly testable hypotheses that could importantly impact on our understanding of the pathophysiology of affective disorders, and suggests novel therapeutic strategies through the enhancement of endogenous compensatory mechanisms. PMID- 1445966 TI - Cardiovascular, neuroendocrine, and sedative responses to four graded doses of clonidine in a placebo-controlled study. AB - Effects of four doses of the alpha 2-receptor agonist clonidine (CLO) (0.25, 0.5, 1, and 2 micrograms/kg IV) and placebo were studied in seven healthy men who volunteered in a double-blind randomized design in order to delineate possible presynaptic and postsynaptic components in the mechanism of action of CLO. Blood pressure, heart rate, plasma noradrenaline (NOR), plasma 3-methoxy-4 hydroxyphenylglycol (MHPG), plasma growth hormone (GH), and subjective sedation were monitored for a period of 1 hr following infusion of CLO. NOR and MHPG were also analyzed in urine, collected at 1 and 4 hr after the infusions. Dose dependent decrements were observed in systolic and diastolic blood pressure and plasma NOR levels, and dose-dependent increases in subjective sedation and plasma GH. CLO did not influence plasma MHPG levels, whereas only urinary MHPG excretion was reduced 4 hr after infusion of 2 micrograms/kg CLO. Because no obvious differences between dose-response relations of plasma NOR (believed to be a presynaptic and peripheral effect), blood pressure (believed to be mainly a central presynaptic and postsynaptic effect), and subjective sedation (believed to be a central and probably postsynaptic effect) were observed, our results do not provide simple parameters to discern the multiple mechanisms of action of CLO. However, at a dose of 0.5 micrograms/kg CLO (a dose lower than that generally used) clear effects on plasma NOR, blood pressure, and sedation, but not on plasma GH (a central postsynaptic effect) or urinary MHPG (a presynaptic effect), were observed. When using CLO as a challenge test in psychiatric disorders, a design with 0.5 micrograms/kg CLO, in addition to the traditional 2 micrograms/kg CLO, may provide more information to characterize discrete abnormalities in the noradrenergic system at the level of the brainstem, the pituitary, or the peripheral sympathetic nervous system. PMID- 1445967 TI - Pain perception in self-injurious patients with borderline personality disorder. AB - Pain ratings during the cold pressor test were significantly lower in female inpatients with borderline personality disorder who report that they do not experience pain during self-injury (BPD-NP group, n = 11), compared with similar patients who report that they do experience pain during self-injury (BPD-P group, n = 11), and normal female subjects (n = 6). Pain ratings were not significantly different in the BPD-P and normal control groups. Self-report ratings of depression, anger, anxiety, and confusion were significantly lower, and ratings of vigor significantly higher following the cold pressor test in the BPD-NP group, but not in the BPD-P group. Only anxiety was significantly lower in the normal control group following the cold pressor test. The implications and limitations of these preliminary findings are discussed. PMID- 1445968 TI - Beta endorphin levels during heroin, methadone, buprenorphine, and naloxone challenges: preliminary findings. AB - Beta endorphin (BE) is a polypeptide agonist for the brain's endogenous opioid system. Levels of BE are elevated by opioid antagonists such as naloxone and depressed by short-acting agonists such as heroin and morphine; they become normalized during steady-state methadone. Buprenorphine (BUP) is a partial opioid agonist whose effects on BE levels were examined in six former heroin addicts and 14 methadone-maintained patients before and after being switched to sublingual BUP 2 mg daily for 1 month. In six former methadone-treated subjects BE levels also were measured after stopping BUP and after naloxone challenge. Levels of BE were not significantly lower in subjects started on BUP after stopping heroin (n = 6) (8.0 versus 8.1 ng/ml) or in subjects started on BUP after stopping methadone (n = 14) (11.6 vs 15.6 ng/ml). However, BE levels were lower on BUP than after naloxone challenge (n = 6) (7.0 versus 34.9 ng/ml). Levels of BE did not significantly change between the first 2 weeks ("early") and "later," although BE levels on methadone significantly correlated with BE levels on BUP in the "early" but not the "later" phase. The BE levels on BUP also did not differ from BE levels of unmedicated normals. PMID- 1445969 TI - Neuropsychological function and REM sleep in schizophrenic patients. AB - To test the hypothesis that rapid eye movement (REM) sleep in schizophrenic patients is associated with cognitive function, we studied 18 schizophrenic inpatients by means of electroencephalograms taken during sleep in their own hospital beds after a minimum 2-wk medication withdrawal period. Patients underwent neuropsychological tests to measure memory function and other aspects of cognitive performance. REM sleep measures demonstrated positive and negative correlations with cognition and memory measures, depending on when REM occurred after sleep onset. Minutes of REM sleep and REM density in the first period correlated negatively with performance, while REM minutes occurring after the first REM period correlated positively with neuropsychological performance. Further work should test whether phasic REM sleep regulation at the beginning of the night plays a compensatory role for neuropsychological dysfunction in schizophrenics. PMID- 1445970 TI - Lactate sensitivity in sleeping panic disorder patients and healthy controls. PMID- 1445971 TI - Intravenous cocaine challenges during naltrexone maintenance: a preliminary study. PMID- 1445972 TI - Infections caused by Chlamydia pneumoniae strain TWAR. PMID- 1445973 TI - Impaired activity of natural killer cells in patients with acute brucellosis. AB - Researchers have claimed that natural killer (NK) cells are involved in the mechanisms of defense of the host against infections. We have investigated the activity of NK cells in peripheral blood mononuclear cells (PBMNC) from 12 patients for whom acute brucellar infection has been diagnosed and from 14 healthy controls. The sera of eight of the patients were also analyzed 3 months after initiation of a 45-day course of antibiotic treatment, at which time they had no evidence of relapse. PBMNC from patients with acute brucellar infection showed a significantly depressed NK cell activity (P < .01) when compared with those from healthy controls; this depressed activity was not related to a deficient number of NK cells since the numbers of CD56+ and CD16+ cells present in PBMNC were similar in patients and controls. Incubation of PBMNC from patients with acute brucellar infection with recombinant interleukin-2, but not with interferon-gamma, can correct this impaired cytotoxic activity. In treated patients, there was a significant enhancement (P < .05) and normalization of the previously defective NK cell activity. It is concluded that acute brucellar infection is associated with a deficient cytotoxic activity of NK cells that can be overcome by in vitro incubation with interleukin-2 and that reverts to normal after antibiotic treatment. PMID- 1445974 TI - Anaerobic osteomyelitis in patients with Gaucher's disease. AB - Bone involvement in patients with Gaucher's disease is common, and some of its clinical manifestations may resemble acute osteomyelitis. In addition, many studies have emphasized the high risk of secondary infection when surgical procedures are performed at the site of the involved bone. Nevertheless, these infections have never been well documented in the literature. Presentation of a patient with Gaucher's disease and osteomyelitis due to Prevotella (Bacteroides) melaninogenica provided us the opportunity to review 10 other similar case reports documented in the literature since 1966. This review suggests that acute hematogenic osteomyelitis is an uncommon complication of Gaucher's disease, but it is of interest that in most cases it is due to unusual organisms, particularly anaerobes. PMID- 1445975 TI - Imported malaria in the Bronx: review of 51 cases recorded from 1986 to 1991. AB - The cases of 51 patients with malaria seen at the Albert Einstein College of Medicine hospitals from January 1986 to June 1991 are reviewed. Thirty-five patients acquired infection on journeys to their country of origin. Of these 35 patients, 83% of whom had lived in the United States for > or = 2 years, only 17% received antimalarial prophylaxis. Ten of the 51 patients were born and raised in the United States, and 70% received prophylaxis (P < .01). Six of the 51 patients were visitors to the United States from areas endemic for malaria. Overall, 64% of patients acquired malaria in West Africa, south of the Sahara; 20% in Asia; 8% in Ecuador; 6% in Haiti; and 4% in the Middle East. The majority of infections were due to Plasmodium falciparum. Six patients traveled to a zone endemic for malaria while pregnant, and none received prophylaxis. In nine of 13 patients who received prophylaxis, there was inadequate dosing or poor compliance. Individuals born in regions endemic for malaria are at high risk of acquiring malaria on return to their countries of origin and are less aware of the need for malaria prophylaxis than are other travelers. PMID- 1445976 TI - Azole therapy for trichosporonosis: clinical evaluation of eight patients, experimental therapy for murine infection, and review. AB - We studied the in vivo antifungal activity of azoles in humans and in a murine model of disseminated trichosporonosis. Eight patients infected with Trichosporon species were treated with fluconazole, SCH 39304, or miconazole for 2-26 weeks. Four patients had fungemia, two patients had disseminated trichosporonosis, and one patient each had soft-tissue infection and cystitis. Response of trichosporonosis to azoles was seen in all eight patients, although one patient died with disseminated aspergillosis while still receiving SCH 39304. A literature review indicated that responses to ketoconazole or miconazole were noted in four patients with trichosporonosis. In the experimental infection, amphotericin B, SCH 39304, and fluconazole were effective in prolonging survival and reducing fungal counts in the kidneys of mice infected with a clinical strain of Trichosporon beigelii. Fluconazole but not amphotericin B prolonged survival of mice infected with a clinical strain of Trichosporon capitatum. We conclude that azoles represent effective therapy for infection with Trichosporon species. PMID- 1445977 TI - Persistence of serum antibodies to Borrelia burgdorferi in patients treated for Lyme disease. AB - To determine if antibodies to Borrelia burgdorferi persist after antibiotic treatment, we recalled 32 patients with Lyme disease from a primary care practice a mean of 16 months after treatment and analyzed initial and follow-up serum samples by ELISA and immunoblot assays. Of the eight patients whose initial serum specimens were positive for IgM antibody by ELISA, three had positive titers of IgM antibody at follow-up; of the 23 patients whose initial serum specimens were positive for IgG antibody by ELISA, 19 had positive titers of IgG at follow-up. Of the five patients whose initial serum specimens were positive for IgM antibody by immunoblot, two had positive titers of IgM antibody at follow-up; of the 30 patients whose initial serum specimens were positive for IgG antibody by immunoblot, 29 had positive titers of IgG antibody at follow-up. The bands on the IgG immunoblot remained remarkably constant during the period from analysis of the initial specimen to that of the follow-up specimen. Nine of the 32 patients had persistent or recurrent symptoms, and ELISA and immunoblot were not helpful for identifying these nine patients. PMID- 1445978 TI - Capsular types of Streptococcus pneumoniae isolated from blood and CSF during 1982-1987. AB - Knowledge about the type distribution of Streptococcus pneumoniae is fundamental to ensure an effective formulation of pneumococcal vaccine, especially with the possibility of producing a polysaccharide-protein-conjugated vaccine for the prevention of invasive disease in children. During the 6-year period 1982-1987, we received and typed 10,298 isolates from patients with invasive pneumococcal disease: 7,812 (76%) from blood and 2,486 (24%) from CSF. Of all isolates, 81% were recovered from individuals in Europe and 23% were from children. In order of frequency, S. pneumoniae types 6A + 6B, 14, 18C, 19F, 1, 7F, 23F, 19A, 4, and 5 were most commonly isolated from children, and types 3, 1, 14, 7F, 4, 6A + 6B, 8, 23F, 9V, and 19F, from adults. The pneumococcal types in the currently available 23-valent vaccine represented 87% of all isolates in this study, but the proportion of vaccine types varied somewhat with age and source. In all pneumococcal groups included in the vaccine, the vaccine types represented > 80% of the isolates, except in groups 6, 15, and 18. PMID- 1445979 TI - Extraparenchymal neurocysticercosis: report of five cases and review of management. AB - Neurocysticercosis due to parenchymal cysts carries a good prognosis regardless of therapy. Extraparenchymal neurocysticercosis (including ventricular, spinal, and subarachnoid types) carries a poorer prognosis. Most extraparenchymal cases present with hydrocephalus. Medical treatment alone in doses and schedules developed for parenchymal disease is frequently unsuccessful. For ventricular disease, most cases can be managed with shunting procedures either alone or together with the administration of antiparasitic agents (e.g., praziquantel or albendazole), without extirpation of the cysts. Subarachnoid disease was formerly associated with a case fatality rate of about 50%. However, with the combination of shunting procedures for hydrocephalus, antiparasitic agents, and, in some cases, surgical extirpation of the cysts, the prognosis is much improved. Spinal cysticercosis can be either leptomeningeal (which responds like subarachnoid disease) or intramedullary. For all forms of neurocysticercosis, the role of antiparasitic agents needs to be better defined. PMID- 1445980 TI - Chronic fatigue syndrome. AB - Chronic fatigue syndrome (CFS) is defined by symptoms and diagnosed without any objective diagnostic tests. Risk factors for developing CFS may include infection, psychiatric disorders, and allergies. Modest dysfunction of multiple organ systems, including the immune, central nervous, endocrine, and muscular systems, have been identified in cases of CFS. Symptoms of various organic, psychiatric, and poorly understood disorders overlap those of CFS. There is no known cure for CFS; however, exercise, counseling, and medications may provide symptomatic relief. PMID- 1445981 TI - beta-Lactam resistance in gram-negative bacteria: global trends and clinical impact. AB - Microbial drug resistance is an inescapable consequence of the utilization of antimicrobial agents in a given environment. Nowhere is the importance of resistance more evident than among agents of the beta-lactam family. Trends toward increased resistance can be seen among fastidious gram-negative bacteria like Haemophilus influenzae, where ampicillin resistance varies from 1% to 64% globally. For Escherichia coli, ampicillin resistance has risen to > or = 50% in high-risk populations, and resistance to third-generation cephalosporins is now being seen in certain areas. Inducible beta-lactamases have been responsible for increasing multiple beta-lactam resistance among certain Enterobacteriaceae and Pseudomonas aeruginosa, and this has been associated with increased use of newer cephalosporins. Xanthomonas maltophilia with its two inducible beta-lactamases is becoming an increasingly important nosocomial pathogen, especially in areas of heavy imipenem utilization. Only through the recognition of factors associated with increasing resistance and the mechanisms responsible can strategies be designed for minimizing beta-lactam resistance. PMID- 1445982 TI - Antibiotic-induced release of endotoxin: a reappraisal. AB - A three- to 20-fold increase in the total concentration of endotoxin occurs as a consequence of antibiotic action on gram-negative bacteria both in vitro and in vivo. There is considerable overlap between the effect of beta-lactam antibiotics and non-beta-lactam antibiotics. Moreover, there is an unexplained delay between the lethal activity of antibiotics and the release of endotoxin. Hence, the mechanism whereby antibiotic action leads to the release of endotoxin is unclear, and mechanisms other than bacterial lysis warrant consideration. The evidence that the release of endotoxin has clinical importance is conflicting, and the issue is unresolved. However, nonlytic release may have implications for the therapeutic efficacy of antiendotoxin immunotherapy. Although frequently cited in the context of the antibiotic-induced release of endotoxin, a number of important differences pertain to conditions, such as the Jarisch-Herxheimer reaction and the tumor lysis syndrome, for which there is clear evidence of an initial deterioration with effective therapy. PMID- 1445983 TI - Significant infections due to Bacillus species following abrasions associated with motor vehicle-related trauma. AB - Non-anthracis Bacillus species are ubiquitous gram-positive spore-forming organisms that were once believed to be nonpathogenic but are now recognized as causing a variety of infections. We report a new aspect of trauma associated with bacillus infection: clinically significant infection by Bacillus species in patients who are involved in motor vehicle accidents and sustain injury related to road contact. Cases were evaluated retrospectively from May 1990 through December 1991. Four patients who had documented infections with Bacillus species and who were involved in motor vehicle accidents associated with road trauma were identified during this period. The antibiotic susceptibility profile of the Bacillus species consistently demonstrated resistance to beta-lactam antibiotics. This series of cases illustrates an additional aspect of disease associated with bacteria of the Bacillus species that should be considered for patients who have sustained injuries from motor vehicle accidents associated with road trauma. PMID- 1445984 TI - Pseudallescheria boydii endocarditis of the pulmonic valve in a liver transplant recipient. AB - We describe a case of Pseudallescheria boydii endocarditis involving the pulmonic valve in an orthotopic liver transplant recipient. The patient required transplantation because of hepatic failure secondary to chronic active hepatitis B. His postoperative course was complicated by surgery for gastric and duodenal ulcers, persistent fever, and, ultimately, sepsis leading to oliguric renal failure. Two days before death, the patient experienced complete heart block, and an echocardiogram revealed pulmonic valve thickening and an endocardial mass along the left side of the septum. At autopsy the patient was found to have a vegetation on the pulmonic valve and a septal abscess. There were multiple fungal emboli found throughout other organs, and P. boydii was obtained on culture. This unique association between pulmonic valve endocarditis and myocardial septal abscess is discussed. In addition, review of the five previous cases of P. boydii endocarditis reveals that this rare infection is associated with immunosuppression and prosthetic devices. PMID- 1445985 TI - Concomitant esophageal and penile ulcerations healed with steroid therapy in a patient with AIDS: case report. AB - A 50-year-old man with AIDS developed concomitant esophageal and penile ulcerations. An etiology could not be found despite intensive investigation. Both ulcers healed after treatment with corticosteroids. To our knowledge, such a situation has been described only for aphthous ulcerations involving the mouth, oropharynx, or esophagus. PMID- 1445986 TI - Cefotetan-induced immune hemolytic anemia. AB - Immune hemolytic anemia due to a drug-adsorption mechanism has been described primarily in patients receiving penicillins and first-generation cephalosporins. We describe a patient who developed anemia while receiving intravenous cefotetan. Cefotetan-dependent antibodies were detected in the patient's serum and in an eluate prepared from his red blood cells. The eluate also reacted weakly with red blood cells in the absence of cefotetan, suggesting the concomitant formation of warm-reactive autoantibodies. These observations, in conjunction with clinical and laboratory evidence of extravascular hemolysis, are consistent with drug induced hemolytic anemia, possibly involving both drug-adsorption and autoantibody formation mechanisms. This case emphasizes the need for increased awareness of hemolytic reactions to all cephalosporins. PMID- 1445987 TI - Factors influencing prognosis in bacteremia due to gram-negative organisms: evaluation of 448 episodes in a Turkish university hospital. AB - A total of 448 episodes of bacteremia due to gram-negative organisms observed during the 7-year period between 1983 and 1989 at Hacettepe University Hospitals were studied for evaluating the factors influencing the prognosis. The overall mortality rate was 45.0%. The mortality rates were not significantly different in "rapidly fatal" and "ultimately fatal" disease groups (48.3% and 45.5%, respectively), whereas it was significantly less (34.8%) in the "nonfatal" disease group compared with the "rapidly fatal" category. There were great differences in the mortality rates among different diseases within the same disease category. Shock, multi-organ failure, source of infection, hospital service, appropriateness of antibiotic therapy, and place of acquisition of infection were found to affect prognosis significantly in multivariate analysis. In conclusion, the identification of prognostic factors is a further step for making necessary interventions in reducing the mortality rate associated with bacteremia due to gram-negative organisms. Underlying disease is still an important prognostic factor; however, a new approach is needed for classification of underlying diseases. PMID- 1445988 TI - Acute renal failure in patients with severe falciparum malaria. AB - Since 1988 in this referral center for severe cases of malaria for South Vietnam, a specialist team has managed malaria-associated renal failure (MARF) with peritoneal dialysis, and the mortality rate of MARF has fallen from 75% (78 of 104) to 26% (27 of 104) (P < .0002). Sixty-four patients with MARF (of whom 12 died) were compared to 66 patients with severe malaria whose serum creatinine levels remained < 250 mumol/L (six died). MARF had the clinical and biochemical features of acute tubular necrosis and was significantly associated with liver dysfunction (P < .05). A fatal outcome was associated significantly with anuria, a short history of illness, multisystem involvement, and high parasitemia. Most patients died from complications related to renal failure. Recovery of renal function was unrelated to parasitemia or hemoglobinuria; the median (range) time until urine output exceeded 20 mL/(kg.d) was 4 (0-19) days, and the time (mean +/ SD) for serum creatinine level to return to normal was 17 +/- 6 days. MARF can be managed effectively by prompt and careful peritoneal dialysis, but more effective dialysis or diafiltration might reduce the mortality rate further. PMID- 1445989 TI - In utero infection due to Pasteurella multocida. PMID- 1445990 TI - Pseudoinfection due to Tsukamurella paurometabolum. PMID- 1445991 TI - Primary abscess of the psoas muscle caused by Streptococcus milleri. PMID- 1445992 TI - Use of zidovudine following occupational exposure to human immunodeficiency virus. PMID- 1445993 TI - QSAR, diagnostic statistics and molecular modelling of 1,4-dihydropyridine calcium antagonists: a difficult road ahead. AB - Quantitative structure-activity relationships of a series of substituted 1,4 dihydropyridine calcium channel antagonists were studied. The analysis is difficult because of the problem of multicollinearity of substituent parameters, a high-leverage point, and position-dependent grouped observations. Canonical regression appears to be the method of choice. With respect to a maximum activity, it was shown that the following rank order of substituent parameters exists: Lipophilicity approximately ortho-position > inductivity > minimum width > meta-position. The molecular conformation of antagonists does not differ markedly (with exception of nifedipine derivatives and nimodipine), but differences seem to exist between the antagonists and the activator BAY K 8644. PMID- 1445994 TI - Evaluation of some N-acyl analogues of 3,5-bis(arylidene)-4-piperidones for cytotoxic activity. AB - The synthesis of fourteen N-acyl derivatives of two 3,5-bis(arylidene)-4 piperidones was accomplished and these compounds were evaluated against L1210 leukemia cells in vitro. With one exception, the compounds had IC50 values of less than 10 microM and six of them had IC50 figures in the 0.2-0.6 microM range which were comparable to a reference drug melphalan. Twelve of the sixteen compounds showed specificity for human leukemia cell lines in the NCI in vitro screen. Studies using 1H NMR spectroscopy revealed that solutions of three N acetylated compounds underwent deamination and possibly other reactions, the deaminated product itself being unstable in the solvent used. PMID- 1445995 TI - Synthesis and antinociceptive activity of 1-[2-(pyridyl)ethyl] and 1-[2 (dihydropyridyl)ethyl] analogues of fentanyl. AB - The syntheses and antinociceptive activities of all three isomeric 1-[2 (pyridyl)ethyl]-4-(propionanilido)-piperidine isosteres (11a-c) of fentanyl (1) are described. The 2- (11a), 3- (11b) and 4-pyridyl (11c) isomers exhibited 10, 2 and 0.2 times the antinociceptive activity of fentanyl, respectively. The ED50 values for 11a, 11b, 11c and fentanyl in the rat 4% NaCl-induced writhing test were 0.00023, 0.00085, 0.0087 and 0.0021 mg/kg sc, respectively. The 3-pyridyl (11b) and 4-pyridyl (11c) compounds were further elaborated to the 6-phenyl-1,6 dihydropyridine (12), C-2 H, Me, n-Bu and Ph 1,2-dihydropyridine (13a-d) analogues having a phenoxycarbonyl substituent on the dihydropyridine ring nitrogen. The most active compound in this series was 1-(2-[3-(1-phenoxycarbonyl 6-phenyl-1,6-dihydropyridyl)ethyl ])-4- (propionanilido)piperidine (12), which provided a 58% inhibition of writhing at a dose of 0.4 mg/kg sc. 1-(2-[4-(1 phenoxycarbonyl-1,2-dihydropyridyl)ethyl])-4- (propionanilido)piperidine (13a) exhibited an ED50 of 1.3 mg/kg sc, indicating a decrease in antinociceptive activity of about a 100 fold relative to the parent 4-pyridyl compound (11c). The dihydropyridine analogues 12 and 13 exhibit substantial antinociceptive activity relative to meperidine (ED50 = 0.6 mg/kg sc). The muscular rigidity effect induced by the pyridine compounds (11a-c) at a dose of 4 mg/kg sc, was not illicited by the dihydropyridine analogues at the same dose, or at a high dose of 40 mg/kg sc (13a). Compounds 12 and 13 may therefore be useful lead compounds for the development of more useful 4-anilidopiperidines if the antinociceptive activity can be dissociated from the muscular rigidity effect. PMID- 1445996 TI - Synthesis and calcium channel antagonist activity of dialkyl 1,4-dihydro-2,6 dimethyl-4-[3-(1-methoxy-carbonyl-4-substituted-1,4- dihydro-pyridyl)]-3,5 pyridinedicarboxylates. AB - A novel class of dialkyl 1,4-dihydro-2,6-dimethyl-4-(3-[1- methoxycarbonyl-4-(H, Me, n-Bu or Ph)-1,4-dihydropyridyl])-3,5-pyridinedicarboxylates (3-29) were synthesized and evaluated as calcium channel antagonists using the muscarinic receptor mediated Ca2+ dependent contraction of guinea pig ileal longitudinal smooth muscle (GPILSM). The differences in activity among members of this new class of compounds was less than one log unit (IC50 range of 8.25 x 10(-6) to 4.36 x 10(-7) M), relative to the reference drug nifedipine (IC50 = 1.43 x 10(-8) M). Compounds possessing symmetrical C-3(5) diethoxycarbonyl ester substituents generally exhibited optimum activity. The R3 substituent (H, Me, n-Bu, Ph) at the 4-position of the 4-[3-(1-methoxycarbonyl-1,4-dihydropyridyl)] moiety was a determinant of activity. In symmetrical diester compounds, a R3 H substituent provided optimum activity for Me, i-Bu and t-Bu dialkyl ester analogues, whereas a R3 Ph substituent provided optimum activity for Et and i-Pr symmetrical diesters. The test results indicate the 4-[3-(1-methoxycarbonyl-4-substituted-1,4 dihydropyridyl)] substituent in this new class of compounds is bioisosteric with a 4-(3-nitrophenyl), or a 4-(3-pyridyl) substituent in classical 1,4 dihydropyridine antagonists. Compounds possessing large symmetrical dialkyl ester substituents (i-Bu, t-Bu), in conjunction with a 4-[3-(1-methoxycarbonyl-4-methyl 1,4-dihydropyridyl)] substituent, permanently inhibited recovery of the KCl induced response in GPILSM. PMID- 1445997 TI - Environmental carcinogens that may be involved in human breast cancer etiology. PMID- 1445998 TI - Formation, characterization, and toxicity of the glutathione and cysteine conjugates of toxic heptapeptide microcystins. AB - Microcystins LR, YR, and RR, cyclic heptapeptide hepatotoxins produced by cyanobacteria, were synthetically converted into glutathione (GSH) and cysteine (Cys) conjugates. Fast atom bombardment mass spectra showed [M + H]+ ions corresponding to GSH and Cys conjugates of microcystins LR, YR, and RR for the obtained compounds. 1H NMR spectral analyses revealed that two singlet signals of olefinic protons of N-methyldehydroalanine (Mdha) in microcystins disappeared in the conjugates, confirming that thiols of GSH and Cys added nucleophilically to the alpha, beta-unsaturated carbonyl of the Mdha moiety. On examination of the 50% lethal dose (LD50) with intravenous injection using mice, both GSH and Cys conjugates showed reduction in toxicity compared with microcystins, but their toxicity still remained. Microcystin LR and its GSH conjugate were separated and identified in a standard mixture by using a frit-fast atom bombardment liquid chromatography/mass spectrometry (Frit-FAB LC/MS) method. Obtained conjugates in the present study would be important compounds as the standard samples for study of metabolism of microcystins, and the Frit-FAB LC/MS method would be applicable to mass spectrometric identification of metabolites of microcystins. PMID- 1445999 TI - Synthesis of 2'-deoxy-7,8-dihydro-8-oxoguanosine and 2'-deoxy-7,8-dihydro-8 oxoadenosine and their incorporation into oligomeric DNA. AB - Reliable methods have been developed for the synthesis of the 3'-O [(diisopropylamino) (2-cyanoethoxy)phosphino]-5'-O-(4,4'- dimethoxytrityl) derivatives of 2'-deoxy-7,8-dihydro-8-oxoguanosine (8-oxo-dGuo, 1) and 2'-deoxy 7,8-dihydro-8-oxoadenosine (8-oxo-dAdo, 2), and for the efficient incorporation of the latter into oligomeric DNA. Both methods rely on the conversion of the 2' deoxy-8-bromopurine nucleosides 3 and 10 to their corresponding 2'-deoxy-8 (benzyloxy) nucleosides 4 and 12 followed by catalytic hydrogenation to generate the 8-oxo function at the C-8 position. The preparation of the phosphoramidites 8 and 19 required for the synthesis of a series of DNA oligomers was carried out under strictly anhydrous conditions. Failure to keep the systems dry resulted in great difficulties during the purification procedures, and erratic results when DNA synthesis was attempted. In the preparation of the DNA itself, it was found to be extremely important during the ammonia deprotection step to add an antioxidant. Otherwise aerial oxidation resulted in almost complete loss of the oligomer. However, when these special conditions were followed, oligomeric DNA containing 8-oxo-dGuo and 8-oxo-dAdo residues could be prepared in excellent yield. Analysis of selected DNA oligomers by enzymatic degradation and mass spectroscopic analysis confirmed the designated sequences and compositions. PMID- 1446000 TI - A study of inactivation reactions of N-acetylcysteine with mucochloric acid, a mutagenic product of the chlorination of humic substances in water. AB - The Salmonella typhimurium (TA100) mutagenic compound, mucochloric acid [3,4 dichloro-5-hydroxy-2(5H)-furanone (MCA)], was inactivated by in vitro N acetylcysteine (NAC). The reaction of MCA with NAC at pH7 was second order and gave products 4, 5, and 6a that resulted from the displacement of chlorine from C 3 or C-4 of MCA. The sodium borohydride treatment of product 4 gave the same product (7) as was obtained by treating 3,4-dichloro-2(5H)-furanone with NAC. The treatment of MCA with (R)-(+)-cysteine gave the bicyclic product 9a, in which the two chlorine atoms of MCA were still present. This product was slightly more mutagenic than MCA, whereas product 5 was less mutagenic than MCA and product 4 was nonmutagenic in the Salmonella typhimurium (TA100) assay. PMID- 1446001 TI - Studies on 1,2,3,6-tetrahydropyridine derivatives as potential monoamine oxidase inactivators. AB - The Parkinsonian-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and close structural analogs are the only known cyclic tertiary amines with good monoamine oxidase substrate properties. In addition to its excellent substrate properties, MPTP is a mechanism-based inactivator of monoamine oxidase B (MAO-B). In an attempt to exploit the special interactions between this cyclic tertiary allylamine and MAO-B, we have initiated studies to evaluate the enzymatic and biological properties of MPTP analogs bearing functional groups which are known to mediate the metabolism-dependent inactivation of this enzyme. This paper describes the synthesis, enzyme substrate/inhibitor properties, and neurotoxic/neuroprotective properties of 1-cyclopropyl-4-phenyl-1,2,3,6 tetrahydropyridine, the corresponding acyclic secondary amine (E)-4-cyclopropyl-2 phenyl-2-butene, and 4-cyclopropyl-1-methyl-1,2,3,6-tetrahydropyridine. PMID- 1446002 TI - 1,N2-ethenodeoxyguanosine: properties and formation in chloroacetaldehyde-treated polynucleotides and DNA. AB - 1,N2-Etheno-2'-deoxyguanosine (1,N2-epsilon dGuo), not previously reported as a product of chloroacetaldehyde (CAA) reaction, has been synthesized and characterized. Reaction of deoxyguanosine with CAA in dimethylformamide in the presence of K2CO3 led to preparation of pure 1,N2-epsilon dGuo with 55% yield. pKa values are 2.2 and 9.2. The anionic form of the compound exhibits weak but defined fluorescence; the intensity is similar to that of N2,3-etheno-2' deoxyguanosine (N2,3-epsilon dGuo) at neutrality. The stability of the glycosyl bond of 1,N2-epsilon dGuo (t1/2 = 2.3 h at 37 degrees C, pH 1) is 10-fold greater than of unmodified deoxyguanosine and at least one thousand-fold greater than of isomeric N2,3-epsilon dGuo. Reaction of CAA with model polynucleotides indicates that hydrogen bonding of guanine residues in the double-stranded structures is, as expected, an important factor in the formation of 1,N2-ethenoguanine. In contrast, the formation of isomeric N2,3-ethenoguanine is relatively independent of whether the DNA is single- or double-stranded. In salmon sperm DNA, reacted with CAA at neutrality, the formation of 1,N2-ethenoguanine could be demonstrated. However, we find the efficiency of formation of this adduct in double-stranded DNA to be lower than that of all other etheno derivatives. PMID- 1446003 TI - Metabolism of nicotine by human liver microsomes: stereoselective formation of trans-nicotine N'-oxide. AB - Liver microsomes from humans catalyze the NADPH-dependent oxidation of (S) nicotine. The principal product is the 5'-carbon atom oxidation product, nicotine delta 1',5'-iminium ion, which is efficiently converted to the gamma-lactam derivative cotinine in the presence of aldehyde oxidase. Another major product is nicotine N'-oxide. In contrast to previous reports describing in vitro or in vivo studies, formation of only trans-nicotine N'-oxide was observed. Demethylation of nicotine was not observed. Studies on the biochemical mechanism of nicotine 5 carbon atom oxidation strongly implicate one major cytochrome P-450 isoenzyme (i.e., P-450 2A6) as largely responsible for delta 1',5'-iminium ion formation. Stereoselective formation of trans-nicotine N'-oxide may be catalyzed in large part by the flavin-containing monooxygenase (form II). These conclusions are based on the effects of alternate substrates for the flavin-containing monooxygenase, heat inactivation studies, immunoblot studies, and selective substrates for cytochromes P-450. The results suggest that (S)-nicotine trans N' oxygenation and delta 1',5'-iminium ion formation may be selective probes of human liver flavin-containing monooxygenase form II and cytochrome P-450 2A6 activities, respectively, useful for in vivo phenotyping of humans. PMID- 1446004 TI - The reactions of cis-[Pt(NH3)2(H2O)2]2+ with L-(+)-cystathionine and seleno-L methionine: potential relevance to the molecular basis of cisplatin toxicity. AB - NMR spectroscopic studies indicate that the hydrolysis product of cisplatin, cis [Pt(NH3)2-(H2O)2]2+, reacts readily with the important intracellular thiol L-(+) cystathionine and the amino acid derivative seleno-L-methionine. In both cases, the formation of six-membered mononuclear S,N- or Se, N-chelate rings was established on the basis of [1H], [13C], [77Se], [195Pt], and [13C]-(1H) DEPT (distortionless enhancement by polarization transfer), COSY (correlation spectroscopy), heterocorrelation, and NOE (nuclear Overhauser effect) difference NMR experiments. The formation of these products suggests that related in vivo processes may play a significant role in the toxicity of cisplatin. The potential loss of NH3 in such platinum complexes may lead to additional products over time. PMID- 1446005 TI - Damage to human alpha-1-proteinase inhibitor by aqueous cigarette tar extracts and the formation of methionine sulfoxide. AB - The effects of aqueous extracts of cigarette tar (ACT) on human alpha-1 proteinase inhibitor (alpha 1PI) are examined by determining alterations in the elastase inhibitory capacity (EIC), amino acid residue content, and electrophoretic behavior of the protein. Hydrogen peroxide generated in ACT by autoxidative processes accounts for the major portion of the loss of EIC. This is indicated by several lines of evidence, including the fact that anaerobic incubations of ACT with alpha 1PI cause negligible loss of EIC. The hydrogen peroxide content of the ACT was estimated by measuring the ability of the extracts to oxidize methionine to methionine sulfoxide; hydrogen peroxide concentrations that model those in ACT cause a similar loss in EIC. Exposure of alpha 1PI to ACT leads to methionine sulfoxide as the only detectable amino acid residue modification and explains the loss of EIC. This is the first report to directly demonstrate methionine sulfoxide formation in alpha 1PI exposed to cigarette smoke components in vitro. Similar amounts of methionine sulfoxide are found in alpha 1PI exposed to hydrogen peroxide at the concentrations predicted to be formed in ACT. Nondenaturing PAGE reveals that alpha 1PI exposed to ACT, but not hydrogen peroxide, shows changes in electrophoretic behavior; the changes are nonoxidative in nature and are not related to the loss of EIC. Studies on the effect of chelators on ACT-mediated damage to alpha 1PI indicate some role for metal ions; however, none of the chelators completely protect alpha 1PI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446006 TI - Structures of three new homotyrosine-containing microcystins and a new homophenylalanine variant from Anabaena sp. strain 66. AB - A hepatotoxic strain of cyanobacterium Anabaena sp. 66 was isolated from a hepatotoxic water bloom sample in Lake Kiikkara, Finland. Four cyclic heptapeptide hepatotoxins were isolated and purified by HPLC from cultured cells of this organism. The structures of three new homotyrosine (Hty) containing toxins, [Dha7]microcystin-HtyR (Dha = dehydroalanine) (1), [D Asp3,Dha7]microcystin-HtyR (2), and [L-Ser7]microcystin-HtyR (3), were assigned, based upon amino acid analyses using both a Waters Pico Tag HPLC system and chiral capillary GC, 1H NMR, fast atom bombardment mass spectrometry (FABMS), and collisionally induced tandem FABMS. A new homophenylalanine (Hph) variant of 1, [Dha7]microcystin-HphR (4), was also obtained as a minor component. Compound 3 is most likely a biosynthetic precursor of 1. The four new toxins did not have an N methyl group at the dehydroamino acid or its precursor unit. PMID- 1446007 TI - Comparison of metabolism and toxicity to the structure of the anticancer agent sulofenur and related sulfonylureas. AB - The metabolic formation of p-chloroaniline from the oncolytic agent sulofenur [N (5-indanesulfonyl)-N'-(4-chlorophenyl)urea, LY186641,] and from similar diaryl substituted sulfonylureas, and its possible relevance to the compound's toxicity, was studied. In previous studies it was found that significant amounts of metabolites such as 2-amino-5-chlorophenyl sulfate (II), which is also a metabolite of p-chloroaniline, are formed from sulofenur in mice, rats, monkeys, and humans. The metabolism of N-(4-tolyl)-N'-(2-hydroxy-4-chlorophenyl)-urea (V) was studied, and V was not found to be an intermediate in the metabolic formation of II from the sulfonylurea N-(4-tolyl)-N'-(4-chlorophenyl)urea (LY181984, III). The amounts of this p-chloroaniline metabolite (II) formed in C3H mice from a series of diarylsulfonylureas were found to correlate with the compound's propensities to form methemoglobin, one notable toxicity of p-chloroaniline. This metabolism was also found to correlate with the structure of the arylsulfonyl moiety of the sulfonylurea. Other evidence supports the hypothesis that p chloroaniline is directly formed by metabolism of sulfofenur and similar diarylsulfonylureas as well. Metabolic formation of p-chloroaniline thus appears to be a plausible explanation for the methemoglobinemia and anemia found to be dose-limiting toxicities of sulofenur in Phase I trials. PMID- 1446008 TI - Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone pulmonary metabolism and tumorigenicity in mice by analogues of the investigational chemotherapeutic drug 4-ipomeanol. AB - 4-Ipomeanol (IPO) is an investigational chemotherapeutic drug with specific toxicity toward the lung. It is metabolically activated to reactive intermediates by cytochrome P450 enzymes present in Clara cells. 4-(Methylnitrosamino)-1-(3 pyridyl)-1-butanone (NNK) is a highly carcinogenic tobacco-specific nitrosamine with organo-specificity for the lung. Like IPO, which it resembles structurally, it is metabolically activated by cytochrome P450 enzymes of rat Clara cells. We synthesized nontoxic analogues of IPO and tested their activities as inhibitors of the metabolism and tumorigenicity of NNK. The IPO analogues synthesized were 4 hydroxy-1-phenyl-1-pentanone (HPP), 7-hydroxy-1-phenyl-1-octanone (HPO), 4 hydroxy-1-(2-thienyl)-1-pentanone (HTP), and 4-hydroxy-1-(3-pyridyl)-1-pentanone (HPYP). When added to A/J mouse lung microsomal incubations, all compounds significantly inhibited the oxidative pathways of NNK metabolism--alpha hydroxylation and pyridine N-oxidation--to varying extents. Inhibition of carbonyl reduction of NNK was generally less effective. Inhibition of alpha hydroxylation by IPO, HPP, and HTP was more pronounced in incubations with lung microsomes than with liver microsomes. None of the IPO analogues showed significant toxicity when given to A/J mice at a dose of 25 mumol; IPO itself was lethal at this dose. HPP and HPO, at doses of 25 mumol, significantly inhibited lung tumor multiplicity in mice treated with NNK; the other analogues and IPO itself were ineffective. The results of this study provide new leads for development of inhibitors of NNK metabolism and chemical probes for the active site of P450 enzymes in Clara cells. PMID- 1446009 TI - Neuropathy target esterase inhibitors: 2-alkyl-, 2-alkoxy-, and 2-(aryloxy)-4H 1,3,2-benzodioxaphosphorin 2-oxides. AB - The standard probes used earlier to study neuropathy target esterase (NTE) are N,N'-diisopropyl phosphorofluorodiamidate (mipafox), diisopropyl phosphorofluoridate (DFP), 2-(2-methylphenoxy)-4H-1,3,2-benzodioxaphosphorin 2 oxide (2-CH3C6H4O-BDPO) (the neurotoxic metabolite of tri-o-cresyl phosphate), and dipentyl 2,2-dichlorovinyl phosphate (DDP) with I50s for hen brain enzyme of 7000, 700, 29, and 3 nM, respectively. NTE phosphorylated by DFP and DDP is proposed to undergo alkylation on aging, and this probably also occurs with 2 CH3C6H4O-BDPO. Optimized probes for NTE should meet the following specifications: highest potency achievable; rapid aging perhaps associated with alkylation; preferably a phosphonate so there are only two leaving groups. An attempt was made to achieve these goals in the 4H-1,3,2-benzodioxaphosphorin 2-oxide series by synthesis of 49 analogs systematically varied in the 2-alkyl, 2-alkoxy, or 2 (aryloxy) substituent. Special precautions are required in synthesis of BDPO derivatives because of their potential hazard on human exposure. Thirty of these compounds had NTE I50s lower than 3 nM. Representative high-potency NTE inhibitors in each series are [2-substituent,I50 (nM) for hen and human brain NTE, respectively]: octyl, 0.25 and 0.18; nonyloxy, 0.89 and 0.98; 4 propylphenoxy, 0.82 and 0.77. In comparing these compounds, although the octyl analog is the most potent in vitro NTE inhibitor, the propylphenoxy compound is the most effective in vivo NTE inhibitor and delayed neurotoxicant in hens. These benzodioxaphosphorins are improved probes for investigations on NTE phosphorylation and alkylation in relation to delayed neurotoxicity. PMID- 1446010 TI - Identification of individual benzo[c]phenanthrene dihydrodiol epoxide-DNA adducts by the 32P-postlabeling assay. AB - Purine deoxyribonucleoside 3'-phosphates were reacted separately with the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. Products resulting from the cis and trans opening of the epoxide ring by the exocyclic amino groups of deoxyadenosine and deoxyguanosine 3'-phosphates were separated by high-pressure liquid chromatography and identified by comparison of the observed circular dichroism spectra with the known spectra for the corresponding nucleoside adducts. The 16 structurally identified benzo[c]phenanthrene-purine deoxyribonucleoside 3'-phosphate adducts were then separately postlabeled according to the Randerath method, and the positions of the individual bisphosphates were mapped by thin-layer chromatography. Chromatographic conditions were developed that allowed separation of the four adducts for 3 of the 4 dihydrodiol epoxide isomers. PMID- 1446011 TI - Identification of N-(Deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo [4,5 b]pyridine as the major adduct formed by the food-borne carcinogen, 2-amino-1 methyl-6-phenylimidazo[4,5-b]pyridine, with DNA. AB - The covalent binding of the N-acetoxy-, N-hydroxy-, and nitro derivatives of the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to 2'-deoxyribonucleosides or DNA was investigated in vitro and in vivo. N-Acetoxy PhIP reacted with deoxyguanosine (dG), but not with the other deoxyribonucleosides, to form N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP), whose structure was determined by NMR and mass spectral analyses and by ultraviolet absorption and pH-solvent partitioning characteristics. While reaction of N acetoxy-PhIP with calf thymus DNA at pH 5.0 yielded 5.38 +/- 1.16 nmol of bound PhIP residues/mg of DNA, N-hydroxy-PhIP gave only 0.13-0.23 nmol binding/mg of DNA under identical reaction conditions. Nitro-PhIP produced no detectable binding under these conditions. HPLC analysis of 1-butanol extracts of enzymatically hydrolyzed DNA that had been modified by N-acetoxy-PhIP in vitro showed a major adduct which coeluted with and had an ultraviolet absorption and a mass spectrum that were identical to that of authentic dG-C8-PhIP. 32P Postlabeling analysis of DNA isolated from colon, pancreas, lung, heart, and liver of rats treated orally with PhIP revealed the presence of a major PhIP-DNA adduct. This adduct had chromatographic properties identical to that of the 32P labeled bis(phosphate) derivative of dG-C8-PhIP and represented 35-45% of the total adducts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446012 TI - Reaction of alpha-acetoxy-N-nitrosopiperidine with deoxyguanosine: oxygen dependent formation of 4-oxo-2-pentenal and a 1,N2-ethenodeoxyguanosine adduct. AB - The six-membered heterocyclic nitrosamine N-nitrosopiperidine (NPIP) is an esophageal carcinogen in the rat whereas its five-membered homologue N nitrosopyrrolidine (NPYR) is a liver carcinogen. These contrasting organo specificities may be due to differences between NPIP and NPYR in their metabolic activation to intermediates which bind to DNA. Previous studies have shown that the metabolic activation of NPYR to DNA binding products occurs through alpha hydroxylation. DNA adducts of NPIP have not been characterized. Therefore, we began our studies by investigating the reaction of alpha-acetoxyNPIP with deoxyguanosine. A major adduct, detected by high-performance liquid chromatography with UV detection, was characterized by its UV, 1H-NMR, and MS as 7-(2-oxopropyl)-5,9-dihydro-9-oxo-3-beta-D-deoxyribofuranosylimidazo+ ++[1,2-a] purine. This 7-(2-oxopropyl)-substituted 1,N2-ethenodeoxyguanosine adduct was formed by reaction of 4-oxo-2-pentenal (3-acetylacrolein) with the 1 and N2 positions of deoxyguanosine. Since the formation of 4-oxo-2-pentenal from alpha acetoxyNPIP was unexpected, we investigated the solvolysis of alpha-acetoxyNPIP in more detail. Major products formed in incubations of alpha-acetoxyNPIP for 7 24 h in phosphate buffer (pH 7.0) at 37 degrees C included 4-oxo-2-pentenal (11 21% yield), 4-hydroxypentanal (18-22%), and 5-hydroxypentanal (27-29%). The formation of 4-oxo-2-pentenal required O2. The results of this study demonstrate some unique features of the chemistry of alpha-acetoxyNPIP and the resulting deoxyguanosine adducts which may be related to the carcinogenic activity of NPIP. PMID- 1446013 TI - Identification of a cysteinyl adduct of oxidized 3-methylindole from goat lung and human liver microsomal proteins. AB - 3-Methylindole is a selective pneumotoxin that is oxidized by cytochrome P-450 enzymes to a reactive intermediate. 3-Methyleneidolenine, a methylene imine electrophile, is the postulated reactive intermediate, and it binds to proteins, a reaction that probably initiates the pneumotoxicity of 3-methylindole. Thioether adducts of this electrophile are formed with glutathione in vitro, but the identity of the adducted electrophile with amino acid residues of microsomal proteins had not previously been determined. 3-Methylindole was incubated with NADPH and goat lung or human liver microsomal proteins, and the proteins were hydrolyzed. 3-(Cystein-S-ylmethyl)indole was isolated and identified as the major amino acid adduct of 3-methyleneindolenine, demonstrating that cysteine thiols preferentially attack the exocyclic methylene position and result in a covalently (thioether) attached 3-methylindole residue to these pulmonary and hepatic proteins. These results demonstrate that the putative methylene imine intermediate is indeed the active electrophile that binds to proteins and presumably initiates the toxic events. PMID- 1446014 TI - Pentahaloethane-based chlorofluorocarbon substitutes and halothane: correlation of in vivo hepatic protein trifluoroacetylation and urinary trifluoroacetic acid excretion with calculated enthalpies of activation. AB - The hydrochlorofluorocarbons (HCFCs) 2,2-dichloro-1,1,1-trifluoroethane (HCFC 123) and 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124) and the hydrofluorocarbon (HFC) pentafluoroethane (HFC-125) are being developed as substitutes for chlorofluorocarbons that deplete stratospheric ozone. The structural similarity of these HCFCs and HFCs to halothane, which is hepatotoxic under certain circumstances, indicates that the metabolism and cellular interactions of HCFCs and HFCs must be explored. In a previous study [Harris et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 1407], similar patterns of trifluoroacetylated proteins (TFA-proteins) were detected by immunoblotting with anti-TFA-protein antibodies in livers of rats exposed to halothane or HCFC-123. The present study extends these results and demonstrates that in vivo TFA-protein formation resulting from a 6-h exposure to a 1% atmosphere of these compounds follows the trend: halothane approximately HCFC-123 much greater than HFC-124, greater than HFC-125. The calculated enthalpies of activation of halothane, HCFC-123, HCFC-124, and HFC-125 paralleled the observed rate of trifluoroacetic acid excretion in HCFC- or HFC exposed rats. Exposure of rats to a range of HCFC-123 concentrations indicated that TFA-protein formation was saturated at an exposure concentration between 0.01% and 0.1% HCFC-123. Deuteration of HCFC-123 decreased TFA-protein formation in vivo. Urinary trifluoroacetic acid excretion by treated rats correlated with the levels of TFA-proteins found after each of these treatments. No TFA-proteins were detected in hepatic fractions from rats given 1,1,1,2-tetrafluoroethane (HFC 134a), which is not metabolized to a trifluoroacetyl halide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446015 TI - Metabolism of benzimidazoline-2-thiones by rat hepatic microsomes and hog liver flavin-containing monooxygenase. AB - The metabolism of benzimidazoline-2-thione (I) and the 1-methyl (II) and 1,3 dimethyl (III) derivatives was studied to elucidate the mechanisms of hepatic oxidation for this class of thionosulfur-containing xenobiotics. NADPH-dependent metabolism of I, II, and III to the corresponding benzimidazoles Ia, IIa, and IIIa, respectively, was observed in dexamethasone-pretreated rat hepatic microsomes. III was the only thiocarbamide converted to an amide metabolite (IIIb). The effects of heat and 1-aminobenzotriazole pretreatment suggested that rat hepatic microsomal metabolism of I was catalyzed by the flavin-containing monoxygenase (FMO) only and that of II and III by both FMO and cytochrome P450 isozymes (P450). Addition of 5.0 mM glutathione (GSH) blocked formation of all metabolites from I, II, and III. Highly purified hog liver FMO catalyzed formation of all metabolites observed in rat hepatic microsomal systems. Incubation of III with either rat liver microsomes or with highly purified hog liver FMO in the presence of [18O]water led to ca. 50% incorporation of [18O] into IIIb. When [18O] molecular oxygen was used, ca. 8% incorporation of [18O] into IIIb was observed. Highly purified hog liver FMO also converted I-III to chemically reactive species that covalently bound to protein thiols. In the presence of hog liver FMO, the covalent binding pattern of radiolabeled I-III to bovine serum albumin was essentially identical to that observed for rat hepatic microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446016 TI - [Effects of N-phthalamoyl-L-glutaminic acid, a selective agonist of NMDA receptor, on binding of 3H-L-glutamate with synaptic membranes of the hippocampus]. AB - In the present investigation the interaction of a novel selective NMDA receptors agonist, N-phthalamoyl-L-glutamic acid (PhGA), with the synaptic membranes preparation of human hippocampus was examined against NMDA. It was established that there are two binding sites of 3H-L-Glu, Kd1 = 0.35 +/- 0.11 nM, Bmax1 = 6.5 +/- 2.3 pmol/mg and Kd2 = 51 +/- 12 nM, Bmax2 = 98 +/- 17 pmol/mg. The inhibition constants (Ki) were calculated for NMDA and PhGA and were equal: Ki(NMDA) = 19 microM, Ki (PhGA) = 13 microM, respectively. It was concluded that PhGA is the partial agonist of the NMDA receptors. PMID- 1446017 TI - [Biogenic amines in brain structures of rats of different zoo-social rank during immobilization stress]. AB - The content of monoamines and their metabolites in different parts of the brain: mesencephalic reticular formation, locus coeruleus, sensomotor cortex was studied by high-performance liquid chromatography in rats with different zoo-social position. Content of dopamine and serotonin in the brain structures studied was found to be different in dominants and subdominants. Maximal changes of monoamines under immobilization stress were observed in dominants. PMID- 1446018 TI - [Hypoxemia, acid-base balance shifts and blood system reactions in adaptation mechanisms]. AB - Experiments were carried out on nonanesthetized and anesthetized dogs with open chest. Intravenous norepinephrine infusion (0.1 microgram/kg body weight/min during 25 minutes) simulated physiological stimulation of sympathetic nervous system. In all the cases it was associated with a significant arterial oxygen tension reduction that could be considered as a reaction with an antioxidant trend. At the same time the acid--base balance parameters shift directed to metabolic acidosis was seen that correlated with the hypoxemia significance. Recorded blood picture changes--hemoglobin and hematocrit increase as well as blood sedimentation rate lowering--improved both oxygen transport and utilization. PMID- 1446019 TI - [Sex differences in response to adrenaline in white rats]. AB - Dynamics of changes of and plasma corticosterone was studied in both male and female rats after intraperitoneal injections of adrenaline at a dose of 20 micrograms per 100 g body weight. The control rats were injected with saline. Animals were decapitated 10, 30, 60, 120, 180 and 240 min after the injections. The specific effect of adrenaline was revealed in the first 10 min of adrenaline injection. This effect was significantly increased to 30-60 min after termination of saline--induced activation of the pituitary-adrenal axis. Both saline and adrenaline caused more significant increases in corticosterone levels in female rats than in male ones. There was a significant delay in the return of corticosterone to resting levels in males compared to that in females. It is supposed that the almost two-fold difference in peak plasma corticosterone concentrations observed after stressors may be associated with increased responsiveness of the female hypothalamus with respect to adrenaline secretion. PMID- 1446020 TI - [Use of thermo- and acid-stable proteinase inhibitor to suppress proteolytic activation in pulmonary inflammation]. AB - A comparative study of thermo-acid stable proteinase inhibitor from rabbit serum and commercial drug contrykal was made on rats and in vitro experiments. Both inhibitors in equal doses effectively suppress proteolytic activity during initiation of lung inflammation. It was shown that the thermo-acid stable inhibitor possesses higher than contrykal, antielastase activity. A high effect of the acid stable inhibitors in the treatment of lung disease is suggested. PMID- 1446021 TI - [Effects of blood platelets on generation of free radicals by leukocytes]. AB - The paper is concerned with studies on generation of free radicals by donor leukocytes in plasma rich or poor in platelets. NBT test and chemiluminescence were employed. Platelets are shown to inhibit generation of free radicals. Changes in free radicals generation were studied under stimulation by zymosan and addition of washed platelet fraction. The conclusion is made that platelets inhibit leukocyte generation of free radicals by adsorption factors necessary for this process from plasma. PMID- 1446022 TI - [Isoform pattern of inducible HSP 70 in the rat myocardium after heat shock]. AB - The hsp 70 content was measured in the myocardium of a control rat group, in the group of rats 24 hours following a heat shock and in the group of rats 48 hours after a heat shock. In 24 hours after the heat shock, a major inducible hsp 70 with molecular weight of 71 kDa and pI about 5.8 occurred which was utterly absent in myocardial cytosol from control animals. In addition, there was an increase in polypeptide fraction with molecular weight of 73 kDa and pI about 5.6 (HSX73). In 48 hours after the heat shock, first the inducible hsp 70 with molecular weight of 71 kDa and pI about 5.8 disappeared which was found in 24 hours; secondly, HSX73 decreased to the control level and, thirdly, several isoforms pronouncedly accumulated with molecular weight of about 71 kDa and pI ranging from 5.9 to 6.3. Thus, the isoform composition of stress proteins induced by heat shock strongly depends on the time after the stress exposure. Furthermore, the accumulation of more acidic isoforms precedes the accumulation of alkaline ones. PMID- 1446023 TI - [Prevention of postischemic lesions of the myocardium using liposomes]. AB - The experiments on dogs showed that 60-min blood flow restriction in the left coronary artery branch resulted in pumping and contractile heart dysfunctions. The removal of the blood flow barrier caused reinforcement of the above dysfunctions. The administration of 50 mg/kg liposome prior to reperfusion improved pumping and contractile heart functions and allowed maintenance of stable hemodynamics during the reperfusion. PMID- 1446024 TI - [Effects of different doses of perfluorocarbon emulsion on hemodynamics and contractility of ischemic heart]. AB - The effect of different doses of perfluorocarbon emulsion (5, 10, and 15 ml/kg) on the hemodynamics and contractility of heart was studied on anesthetized dogs. The emulsion was introduced intravenously by the 60th minute of acute myocardium ischemia caused by partial coronary occlusion. When pO2 = 120 mm Hg, the emulsion was efficient only at doses of 10 and 15 ml/kg (an increase in cardiac ejection, in the rate of contraction and relaxation of the myocardium, reduction of vascular resistance). However, the efficiency of the emulsion at a dose of 15 ml/kg was lower, possibly, due to hypervolemia and cardiodepressive effect of introduction of excess quantity of the surface-active substance proxanol, a component of the emulsion. PMID- 1446025 TI - [Activity of antioxidants in serum of animals with experimental crush syndrome]. AB - Ischemia of soft tissues in crush syndrome results in activation of free radical oxidation processes, which negatively effect the functions of many biological systems. The presence of antioxidant system in the body can inhibit the action of free radicals. Antiradical effect of this system is seen in vitamin K, ubiquinone and ascorbic acid. The results of the experiment showed that the quantity of vitamin K, ubiquinone and ascorbic acid increases in the serum of blood after decompression of soft tissues in 14 hours, three and seven days. This fact supports an active participation of antioxidant system in the pathogenesis of crush syndrome. PMID- 1446026 TI - [Determination of esterase activity of human and animal serine proteinases using fluorogenic esters of amino acids as substrates]. AB - Two fluorogenic derivatives of amino acids are proposed as substrates for the purpose of enzymatic assay: N-benzyloxycarbonyl-phenylalanine-4-methyl umbelliferyl ester (substrate-1) and tert-butyloxycarbonyl-alanine-4-methyl umbelliferyl ester (substrate-II). Chymotrypsin-like (hydrolysis of substrate-1), elastase-like (hydrolysis of substrate-II) esterase activity of bovine pancreatic chymotrypsin, activities of cathepsin G and elastase from human, porcine and rat neutrophils and esterase activity of human, porcine and rat serum were assayed. Differences in the level of chymotrypsin-like and elastase-like activities of human, porcine and rat serum were established. Activities of purified elastase and cathepsin G from human and animal neutrophils were shown to have no significant distinctions. PMID- 1446027 TI - [Cytoplasmic casein kinase 2 and its substrate proteins in the brain in Alzheimer's disease]. AB - The absence of casein kinase 2 on blots of temporal cortex extracts from Alzheimer's disease patients (ADP) was shown using antiserum to casein kinase 2. Casein kinase 2 activity towards endogenous substrates and casein is 2-5 times less in ADP brain in comparison to normal controls. The fractions of heparin binding proteins, containing protein substrates for phosphorylation, were isolated from temporal cortex of ADP and normal controls. The total amount of heparin-binding proteins from ADP brains is less than from control brains, and the polypeptide composition of these fractions is much more poop. PMID- 1446028 TI - [Modulating effects of adenosine on the process of human platelet activation]. AB - The inhibitory effect of adenosine on aggregation of human platelets activated by platelet activating factor (PAF), ADP and serotonin (5-HT) were examined using native platelets from blood of volunteers. Platelet aggregation was determined by Born's method. Effective adenosine concentrations (IC50) which had inhibited platelet aggregation were found to be 0.63 +/- 0.11, 1.47 +/- 0.31 and 0.64 +/- 0.18 microM, respectively. It was shown that 10 microM adenosine inhibited PAF induced platelet aggregation completely. The same adenosine concentration blocked ADP- and 5-HT-induced aggregation only partially. Adenosine is physiological inhibitor of human platelet aggregation in administration of PAF, ADP and 5-HT. Specific characteristics of adenosine modulating effect on these ligands was elicited. PMID- 1446029 TI - [Induction of monooxygenase system and incorporation of radioactivity from 2-14C lysine into proteins of rat liver microsomes under the action of phenobarbital and the background of lysine, methionine, threonine and vitamin A, C and E deficiencies]. AB - The effect of diet on induction of monooxygenases and distribution of radioactivity from 2-14-C-lysine in fractions of liver homogenate, muscle homogenate and blood of male rats treated with phenobarbital (80 mg/kg, three days) was studied. 2-14-C-lysine was injected intraperitoneally 24 h before the first injection of phenobarbital. It was demonstrated that monooxygenase induction, increase of relative liver weight and incorporation of radioactivity from 2-14-C-lysine into fractions of liver homogenate in phenobarbital-treated rats fed diet deficient in lysine, methionine, threonine and vitamins A, C and E were more pronounced as compared with the similarly treated rats which were fed a balanced diet. The possibility of mobilization of deficient essential components to liver from other organs and tissues for maintenance of monooxygenase induction is discussed. PMID- 1446030 TI - [A combined effect of cortisol and concanavalin A on calcium ion contents in thymic lymphocytes]. AB - The influence of hydrocortisone (1-10 microM) on mitogen-induced Ca level was studied in cytoplasma thymocytes of rat. The investigation was conducted with the use of fluorescence technique (FURA-2AM). A specific Ca-blocking effect of the hormone was observed in the thymocytes of intact animals. Hydrocortisone did not change Ca-response of mitogen-stimulated hormone-resistant thymic lymphocytes. A conclusion was made about applicability of this method to assess the response of the cells to glucocorticoids in vitro. PMID- 1446031 TI - [Study of the role of different types of glutamate receptors in spatial memory in rats]. AB - A comparative study was performed to assess effects of different antagonists of glutamate receptors on spatial discrimination of rats in 8-arm radial and water mazes. Noncompetitive NMDA receptor blocker MK-801 in the dose 0.10 mg/kg and higher impaired the accuracy of performance in radial maze, whereas in the doses 0.05--0.30 mg/kg in water maze. Quisqualate IAMPA- and 2-amino-4 phosphonobutyrate (2-APB) I antagonists glutamate diethyl ester (250--500 mg/kg) and 2-APB (50--100 mg/kg), respectively, only increased time to complete radial maze performance and failed to alter choice accuracy. Both antagonists at the same doses did not affect performance of water maze task. The involvement of each type of glutamate receptors in different stages of spatial discrimination process in rats was discussed. PMID- 1446032 TI - [Spectral analysis of the effects of nomifensine on bioelectric activity of the rat brain]. AB - The influence of nomifensine on bioelectrical activity of sensorimotor cortex, dorsal hippocamp and lateral hypothalamus in conscious rats in free behavior was studied. The pharmacological and EEG analysis of nomifensine action on EEG power spectra by Fourier technique was measured. It was established that nomifensine evoked an increase and stabilization of the dominant peak in EEG spectra in the left and right cortex and in the left hippocamp, while in the other ranges of frequency a decrease was observed. The effects on hypothalamus was opposite--EEG power spectra decreased in all the ranges. The authors conclude that nomifensine evokes higher level of wakefulness, vigilance of the animals. This is likely to underlie neurophysiological mechanisms of optimal behavior due to stimulants of CNS, including nomifensine. PMID- 1446033 TI - [Effects of chorionic gonadotropin on dynamics of primary immune response]. AB - The effect of chorionic gonadotropin (CG) on primary immune response was estimated according to the level of direct and indirect plaque-forming cells (PFC) on day 5, 8 and 12 after immunization of non-castrated and ovariectomized female mice of CBA strain. It was established, that on the 5th day CG (40-200 IU) did not influence the direct PFC level in ovariectomized animals, but stimulated them in non-ovariectomized mice (40 IU). In ovariectomized animals the selective immunodepressive effect of hormone on the IgG-PFC formation processes has been revealed. The CG effect depended on the time of PFC number examination as well as on the hormone dose. In non-castrated animals, where immunomodulating CG effects are partially mediated by ovarian hormones, the injection of hormone only in the dose of 200 IU significantly lowered the number of IgM and IgG-PFC. It is suggested, that sex steroids on the late stages of PFC formation, when the processes of isotype antibody synthesis switch take place, appear to be synergists of CG immunodepressive effect. PMID- 1446034 TI - [Lymphocyte subpopulation state of the human lung during prenatal development]. AB - Distribution of surface lymphocyte markers was assessed in foetus lung by cytofluorimetry using monoclonal antibodies produced by "Ortho Diagnostic systems" and "Becton Dickinson". Seven lymphocyte subpopulations were detected in developing lungs even at the pseudoglandular stage (8-15 weeks). There was a significant increase in these lymphocyte subpopulations in canalicular stage. Quantity of T3+ cells increased 8-fold and B-cells 10-fold. There was a tendency to increased number of cortical thymocytes (T6+), and to decreased ratio T6+/T3+ lymphocytes. The ratio of immunoregulatory lymphocyte subpopulations (T4+/T8+) resembled that of these subpopulations in adult human lung rather than in cord blood. In canalicular stage the share of lung lymphoid cells in S-phase was decreased. PMID- 1446035 TI - [Role of histamine receptors of mouse and guinea pig peritoneal leukocytes in the pathogenetic effect of Yersinia pestis adenylate cyclase]. AB - The effect of purified preparation of adenylate cyclase isolated from Y. pestis on peritoneal leukocytes of white mice and guinea pigs was investigated. Y. pestis adenylate cyclase was shown to accomplish its pathogenic action via histamine-specific receptors on the surface of eukaryotic cells. The involvement of H1 and H2 histamine receptors on target cells in the adenylate cyclase action leading to development of plague infection is discussed. PMID- 1446036 TI - [Immunity and the stage of carcinogenesis progression (experimental bases of the concept)]. PMID- 1446037 TI - [Quantitative determination of anthracycline antibiotic binding with DNA]. AB - A new method of quantitative intravital assessment of anthracyclines accumulation and binding with DNA in alive cells has been developed. For this purpose DNA specific fluorescent dye Hoechst 33258 was used. Extent of fluorescence quenching of bound with DNA dye correlated with binding of daunomycin with cell DNA after mixing solutions of the drug and cells. It allowed us to determine quantity of drug molecules bound with DNA in the cells during the time. PMID- 1446038 TI - [Differences in anti-oncogene p53 expression in human monocytes and lymphocytes in vitro]. AB - The p53 gene has been associated with malignant transformation as well as "anti oncogene" activity. In the present report expression of p53 in resting and activated human blood monocytes and lymphocytes is analyzed. It is found that human monocytes freshly isolated by continuous percoll gradient centrifugation contained detectable level of p53 mRNA. Stimulation of monocytes by potent activation inducer Staphylococcus Aureus Cowan I for 3-5 hr caused disappearance of r53 mRNA. In contrast, induction of high level of TNF-alpha mRNA was detected. Addition of cycloheximide had no effect on p53 mRNA content in stimulated monocytes, and caused disappearance of mRNA in resting cells. In lymphocytes cultures p53 mRNA was absent in freshly isolated cells and in resting lymphocytes cultured for 20 hr. Activation of lymphocytes by lectin caused accumulation of p53 mRNA. We suggest that r53 gene regulation and functions might be different in human monocytes and lymphocytes. PMID- 1446039 TI - [Physicochemical and functional properties of hemoglobin of mice infected with Ehrlich's carcinoma]. AB - Injection of white mice with Ehrlich's carcinoma triggers an increase in the mice blood erythrocyte fraction suspended in the 14% sucrose concentration zone. As established by acid erythrograms, a quantitative increase of this red blood cell population is due to an increased rate of erythroblast maturation and occurrence of immature cell forms in the blood stream. As shown by alkali denaturation of hemoglobin, tumour development causes an increase in alkali-resistant hemoglobin fraction in the erythrocytes. On the basis of the data on alkali denaturation of hemoglobin, it is suggested that in the infected mice increased rate of erythrocyte maturation go in line with selective binding of alkali resistant hemoglobin fraction to red cell membrane. PMID- 1446040 TI - [Mouse serum inhibition of cytotoxicity of goat antibodies against mouse thymocytes]. AB - It is shown that the serum of Balb/c, C57Bl/6 and F1(C57Bl/6 x CBA) mice inhibits cytotoxicity of goat antithymocyte antibodies. The addition of the serum into the incubation medium increases the proportion of alive cells from -5% up to 95%. Cytotoxicity was also inhibited by the globulin fraction of the mice serum. It is suggested that normal mice serum contains factors which block cytotoxicity of antibodies against antigen host determinants. PMID- 1446041 TI - [Development of long-term post-tetanic potentiation and changes in S-100 protein contents in hippocampal slices of rats in different functional states]. AB - Male rats of the strains with low (LE) high excitability (HE) of the nervous system have been used in this study. Half of the animals of each strain were neurotized in accordance with the Hecht's scheme. In the hippocampal slices of the non-neurotized LE rats there was a significant increase of the populational spike amplitude during development of LTP as compared with the opposite group of the animals. The LTP formation in the LE strain of rats caused a decrease in the S-100 protein content in the water-soluble, and an increase in the membrane-bound fraction of the protein. Similar results we have observed with the non-inbred Wistar rats but not with the HE strain of the animals. The levels of the water soluble S-100 protein fraction were also higher in the hippocampuses and entorenal cortices, but not in the cerebellae of the LE strain, as compared with the HE strain of the rats. No differences have been found in the membrane-bound fraction of S-100 protein. PMID- 1446042 TI - [Effects of acyclic analogs of atrial natriuretic factor on proliferative processes of the epithelial tissue in white rats]. AB - The effect of atrial natriuretic factor (ANF) synthetic linear truncated analogues AP-H-6-OH and AP-FOR-6-OH on corneal, skin, duodenum and colon epithelium proliferation has been studied on male rats. The epithelium mitotic activity and DNA synthesis were evaluated 4 and 24 h after intraperitoneal injection of 10 or 100 micrograms/kg peptides. In a dose of 10 micrograms/kg both ANF synthetic analogues inhibited proliferation processes in corneal epithelium, but activated the DNA synthesis in duodenum and colon epithelium. AP-FOR-6-OH (10 micrograms/kg) decreased the mitotic activity of skin epithelium and increased the silver grain density over the cell nuclei at the same time. 100 micrograms/kg ANF analogues stimulated cell mitogenesis in all organs studied. According to the data obtained ANF linear truncated analogues influence on epithelium proliferation is similar to effector of previously studied cyclic atriopeptin AP II. PMID- 1446043 TI - [Fast transport of proteins in the axons of spinal cord motor neurons in rats adapted and unadapted to physical loading]. AB - The prolonged nonintensive swimming without load (12+ +2 h) provoked a decrease of the rate of fast axonal transport in the motor fibres of the sciatic nerve by 18% and of the overall amount of transported proteins 2-fold as compared with control. The relatively short-term but more intensive activity (swimming with the load 1/11 of body weight during 60+ +10 min.) results in an increase of the rate by 10% and the overall amount of fast transported proteins 2-fold. Daily swimming (3 h. without load and 10-15 min. with load) during 20 days returns the above parametres to the controls. The compensative-adaptive changes of fast anterograde transport are the fact that may be involved in trophic communication between neuron and target cell. PMID- 1446044 TI - [Proliferation and differentiation of nerve cells of the human NN. supraopticus et paraventricularis transplanted to the brain of adult rats]. AB - Human fetal hypothalamic neurosecretory cells (NSC) were studied after transplantation into the third ventricle of the adult rat brain. 3H-thymidine uptake data have shown that the time of origin and proliferation of NSC of grafted tissue and of supraoptic and paraventricular nuclei in normal embryogenesis was similar. Specific staining revealed that the start of neurosecretory function in grafted tissue corresponded to the date when NSC began functioning in normal ontogenesis. PMID- 1446045 TI - [Effects of male sex hormones on specific uptake and release of 3H-serotonin in the rat hypothalamus in vitro]. AB - With the use of "isotopic method" a study was made of the main parameters of functional activity of serotoninergic elements of hypothalamus--the specific uptake and release of 5-OT. The animals used were sexually mature rats castrated on the first postnatal day. In sexually mature intact males the specific uptake of 3H-5-OT by serotoninergic structures of the anterior hypothalamus was significantly lower than in females. Castration of animals on the first day of life resulted in the increase of specific 5-OT uptake in sexually mature males up to that observed in females. There were no differences between the sexes in the rate of spontaneous release of 5-OT. However, response to K(+)-depolarization in the anterior hypothalamus of intact males was significantly lower than that in females. In the hypothalamus of males castrated neonatally the amplitude of the response to the effect of the depolarizing agent was increase up to the level observed in females. By the results obtained it is indicated that elimination of the effect of male hormones on the first postnatal day results in the increase of 5-OT uptake and release in the hypothalamus of sexually mature rat males. PMID- 1446046 TI - [In vitro phenomenon of beta cell migration from fetal calf pseudoislets]. AB - Pseudoislets--pancreatic microfragments containing a lot of beta-cells and capable of insulin secretion in vitro-were obtained from 12 fetal calf pancreata by the use of collagenase. Morphological and functional changes of the pseudoislets were studied during culture. We found a rapid migration of beta cells out of the pseudoislets to the bottom of plastic tissue culture plates. This process was accompanied by a significant decrease of insulin-secreting capacity of the floating microfragments. This should be taken into consideration in cases when pseudoislets are prepared for transplantation in order to avoid beta-cell loss. PMID- 1446047 TI - [Ultrastructural and cytochemical changes in the rat liver during hypoxia tolerance training]. PMID- 1446048 TI - Should women with node-negative breast cancer receive adjuvant chemotherapy?- Insights from a decision analysis model. AB - The use of adjuvant chemotherapy in women with node-negative breast cancer has been controversial and actively debated since the 1988 National Cancer Institute Clinical Alert. We developed a decision analysis model that used the results of available randomized controlled trials to assess the potential clinical and financial effects of using adjuvant chemotherapy for groups of 45-year-old and 60 year-old women. Using the baseline assumptions, we found that chemotherapy increases quality adjusted life expectancy and survival by a substantial amount at a cost comparable to most accepted medical interventions. The model highlights the uncertainties in duration of benefit from therapy, the need for refinements in risk stratification, the importance of patient preferences about toxicity and benefit, and the need for accurate cost-accounting for oncologic therapies. Decision analysis complements other methods for information gathering, analysis, and synthesis used in clinical research. With the increasing focus on the effectiveness of medical interventions, decision analysis will be an important tool for oncologists to understand. PMID- 1446050 TI - Proliferative activity of breast cancers increases in the course of genetic evolution as defined by cytogenetic analysis. AB - The prognostic value of proliferative activity and its relationship with steroid hormone receptors and histopathological grade have been demonstrated for breast cancers. However, nothing is known about the underlying mechanisms. In order to understand the chronology of the appearance of increased proliferative activities, we used a series of 760 consecutive breast cancers for which we had obtained S-phase fractions (SPFs) by DNA flow cytometry. When the absolute difference from a DNA index of 1.00 was compared to SPFs, a significant positive correlation was obtained (r = 0.39, p < 0.0001), indicating that the probability of observing a high SPF increases when tumors progressively deviate from diploidy. A highly significant correlation was observed for the hyperploid group when hypertetraploid tumors were excluded, as the SPFs increased progressively as the DNA indices decreased from 2.00 to 1.30. This observation suggested a relationship with the evolution of chromosomal abnormalities as determined by cytogenetic analysis. Indeed, in a subset of 52 cases for which sufficient metaphases were available, there was a highly significant correlation between the SPF values and the proportion of rearranged chromosomes in the tumor cells (r = 0.60, p < 0.0001). When SPFs were separated into low or high using the median value (4.5%), a correlation also existed with the genetic evolution, since they increased from diploidy to hypodiploidy and then, after endoreduplication, from tetraploidy towards triploidy, as determined by the chromosome counts. Our results substantiate the relationship between proliferative activity and steroid hormone receptors which follow the same model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446049 TI - Contraceptive steroids and the mammary gland: is there a hazard?--Insights from animal studies. AB - The safety of synthetic steroid hormones to be used for contraception in the human female is tested in rats, beagle dogs, and (once marketing starts) in monkeys. Because early studies did not show a mammary tumor stimulating effect in the human, in contrast to findings in the dog, many objections have been raised to the use of the dog for these toxicity studies. It has been claimed that the dog is unique in its sensitivity to the mammary tumor promoting effect of progestins and that this tumorigenic effect results from progestin-induced growth hormone (GH) induction. A thorough review of the literature does not support these claims. Tumor stimulatory effects of progesterone or synthetic progestins can be observed under some conditions in rodents as well as in cats and monkeys. In addition, recent evidence suggests a role for progesterone in mammary tumorigenesis in the human, and contraceptive steroids may also not be completely without risk. While the suggested role for GH in dog mammary tumorigenesis is far from proven, such a role cannot be excluded in the other species. Whether tumor stimulatory effects of sex steroids are based upon induction of proliferation in target cells or upon genotoxic effects or both is not yet certain. PMID- 1446051 TI - Breast tumor-derived factors stimulate reduction of estrone to estradiol in nonmalignant breast tissue. AB - This study examines the paracrine influence by human breast carcinoma cells (UISO BCA-1) on nonmalignant breast tissue in vitro. The 17 beta-OH-SDH-mediated reductive pathway (estrone-->estradiol) was significantly increased in nonmalignant breast tissue coincubated with human breast carcinoma cells, compared to control tissues incubated in the media alone. No influence on the enzyme activity was noticed in coincubated breast cancer cells. Preincubation of breast cancer cells with estradiol (10(-8) M) significantly decreased the enzyme activity in coincubated nonmalignant breast tissue, which was restored to control levels by addition of R5020 (10(-8) M), tamoxifen (10(-6) M), or a combination of both. In nonmalignant tissues incubated in the presence of growth factor TGF alpha, enzyme activity was reduced to between 46% and 76%. No other growth factors (IGF I, IGF II, PDGF) influenced enzyme activity. In nonmalignant tissues incubated with malignant tumor cytosol, enzyme activity was increased in 16% cases, inhibited in 21%, and not significantly changed in 63%. The data from the present study suggest that factors produced by breast carcinoma cells may influence interconversion of estradiol in nonmalignant tissue. In patients, factors produced by malignant tumor mass may have paracrine influence on surrounding nonmalignant breast tissue and, thereby, may influence the estrogen availability to tumor mass. PMID- 1446052 TI - Influence of aminoglutethimide on plasma oestrogen levels in breast cancer patients on 4-hydroxyandrostenedione treatment. AB - The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p < 0.05). Plasma oestrone was suppressed by a mean of 40.6% (p < 0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p < 0.025). Two of the patients, neither of whom had responded to 4 hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer. PMID- 1446053 TI - Cytosol cathepsin-D content and proliferative activity of human breast cancer. The Comitato Italiano per il Controllo di Qualita del Laboratorio in Oncologia. AB - Mitogenic properties have been demonstrated in vitro for the lysosomal acidic protease cathepsin-D (cath-D). We investigated possible relationships between cath-D cytosol cell content and tumor proliferative activity in a series of 129 operable breast cancer patients. For total cytosol cath-D evaluation, a solid phase two-site immunoradiometric assay was utilized on tumor cell cytosol obtained for hormone receptor assay (DCC method). The percentage of S-phase cells was analyzed by 3H-thymidine autoradiographic assay. Median 3H-thymidine Labeling Index (3H-Tdr-LI) of the series was 2.7%; median cath-D content resulted 57 pmol/mg of protein cytosol and was significantly higher in node-positive with respect to the node-negative subgroup (p < 0.03). When classified in low, intermediate or high tumor cath-D content and slow or fast proliferative activity (cut-off: median values of the series), no significant agreement was found between the two variables. Statistical analysis, however, showed that a significant inverse correlation existed in node positive tumors between cath-D and 3H-Tdr-LI values which was even more evident in N-positive high estrogen receptor-positive (ER+) cases (coefficient of correlation = 0.6828; p = 0.0001). Cytosol cath-D content cannot be generally proposed as a direct marker of proliferative activity for operable breast cancer. PMID- 1446054 TI - In memoriam--William L. McGuire. PMID- 1446055 TI - Immunohistochemical reaction to human milk fat globule antibodies and breast cancer differentiation. AB - Immunohistochemical studies of human breast cancers using human milk fat globule (HMFG) antibodies are divergent regarding the association with histologic differentiation. To clarify this association 392 tumors were assessed using two antibodies, HMFG-1 and HMFG-2. In half the tumors studied the tissue reaction to both antibodies was the same and in 63% the site of reaction was identical. Using both univariate and multivariate statistics, a highly significant association was recorded between membrane staining and well differentiated cancers and cytoplasmic staining and poor differentiation. Well differentiated tumors contained significantly more reactive cells. Complementing these findings was the association between age at diagnosis, tumor stage, and estrogen receptor status and differentiation. It is possible that immunohistochemical analysis with HMFG antibodies will provide better characterization of tumor differentiation than morphologic interpretation. PMID- 1446056 TI - Secretion of breast gross cystic disease fluid proteins by T47D breast cancer cells in culture--modulation by steroid hormones. AB - The effect of steroid hormones on modulating the secretion rates of three human breast gross cystic disease fluid proteins (GCDFP-15, GCDFP-24, and GCDFP-44) by T47D breast carcinoma cells in tissue culture was evaluated. Androgens (dihydrotestosterone or fluoxymesterone) were capable of stimulating the secretion rates for all three GCDFP's while showing a minimal trend toward slowing the growth rate of T47D cells. This is the first study which shows that androgens can specifically stimulate all three of the major breast GCDFP's concomitantly. Progesterone, and three synthetic progestins, all showed inhibition of the growth rate of T47D cells while causing enhancement of the secretion of GCDFP-15 and GCDFP-44, and only minimal effect on the secretion rate of GCDFP-24. Estradiol was essentially neutral to the growth rate of the T47D cells in our test system. Estradiol did cause a mild enhancement of GCDFP-44 secretion rate, with no appreciable effect on GCDFP-15 or GCDFP-24 secretion rates. These findings suggest that an androgenic stimulus may be involved in the secretion of GCDFP's associated with breast gross cystic disease. PMID- 1446057 TI - Characterization of two human mammary carcinomas, MT-1 and MT-3, suitable for in vivo testing of ether lipids and their derivatives. AB - The human mammary carcinomas MT-1 and MT-3 originate from surgical material and were transplanted in nude mice. Both tumors have been classified as estradiol- and progesterone receptor-negative. Therapeutic doses of hormones and anti hormones remained without growth inhibitory effect. MT-1 and MT-3 proved to be sensitive to conventional cytostatic drugs used for treatment of mammary carcinomas; striking is their sensitivity to ether lipids. Therefore, they are considered suitable tumor models for this class of substances. PMID- 1446059 TI - High-tech equipment used in your quality program. PMID- 1446058 TI - Control of proliferation of MCF-7 breast cancer cells in a commercial preparation of charcoal-stripped adult bovine serum. AB - A commercial preparation of charcoal-stripped adult bovine serum was used to culture MCF-7 cells in estrogen-free media. Use of this stripped adult bovine serum represents an alternative to calf serum which is in more limited supply, and saves charcoal-stripping of serum in the laboratory, which can be a rate limiting step in the preparation of materials for estrogen-free tissue culture. MCF-7 cell proliferation was controlled by estrogens, epidermal growth factor (EGF) and lithium chloride in adult bovine serum as well as in standard media prepared with charcoal-stripped calf serum, and approximately the same fold increase in response to the tested agents was observed in the two sera. Although the growth rates were lower in media prepared with adult bovine serum, MCF-7 cells in both media exhibited the same sensitivities in dose-responses to these three mitogens. Levels of estrogen and progesterone receptors, and the magnitude of estrogen-dependent stimulation of the progesterone receptors, were similar in cells maintained in both sera. Therefore, a commercially stripped adult bovine serum can be used to replace calf serum in the study of estrogenic responses and the control of proliferation in MCF-7 breast cancer cells. PMID- 1446060 TI - Interdisciplinary guidelines for the management of acute pain: implications for quality improvement. PMID- 1446061 TI - Selecting and using computer application software for quality assessment and improvement. PMID- 1446062 TI - Using a database management system to manage quality assurance data. PMID- 1446063 TI - Automated data entry and analysis for unit-based quality assurance programs. PMID- 1446064 TI - Computerized quality assurance monitoring: a collaborative project. PMID- 1446065 TI - Protecting patient confidentiality in the pursuit of the ultimate computerized information system. PMID- 1446066 TI - A study of clients' perceived needs in a nursing center. PMID- 1446067 TI - Quality: a concept of importance to nursing. PMID- 1446068 TI - Quality-driven information systems: a time to act. PMID- 1446069 TI - Program evaluation of a school-based clinic: one method of demonstrating effectiveness. PMID- 1446070 TI - Emphasis on quality assessment and improvement activities. PMID- 1446071 TI - An indirect mechanism by which a protein from the male gonad hastens salivary gland degeneration in the female ixodid tick, Amblyomma hebraeum. AB - In the adult female tick, Amblyomma hebraeum Koch (Acari: Ixodidae), salivary gland degeneration is triggered by an ecdysteroid, provided the female is above a critical weight (approximately 300-400 mg). In mated females, salivary gland degeneration is virtually complete within 4 days of detachment from the host. In virgin females, salivary gland degeneration is delayed by 4 days. This delay can be reversed by the injection of a male reproductive tract homogenate directly into the hemocoel. In this study, we consider a possible mechanism of action for this "male factor." Once mated, male factor likely gains access to its target tissue(s) as a humoral factor. Male factor, however, appears not to act by sensitizing the salivary glands to the action of ecdysteroids. Instead, it appears to act by accelerating the appearance of ecdysteroids in the hemolymph. PMID- 1446072 TI - Sequence accuracy of large DNA sequencing projects. AB - Very little information has been accumulated regarding the likely accuracy of final or consensus DNA sequence data. With the large-scale efforts anticipated for the Human Genome Project, the subjective determination of final sequence must eventually be replaced with more objective, automatic methods. This will require a much better understanding of the nature of error in raw sequencing data and its impact on the determination of the final sequence. This paper describes a start at defining the error model of large-scale sequencing efforts based on random subcloning strategies. PMID- 1446073 TI - An estimate of the sequencing error frequency in the DNA sequence databases. AB - We have examined vector sequences fortuitously present in the EMBL sequence database as contaminating parts of submitted sequences, and found a sequencing error frequency of 3.55% in this subset of release 27 of the database. We discuss the possibility that this value may be representative for corresponding errors in the database as a whole. PMID- 1446074 TI - Closely linked H2B genes in the marine copepod, Tigriopus californicus indicate a recent gene duplication or gene conversion event. AB - Two nonallelic histone gene clusters were characterized in the marine copepod, Tigriopus californicus. The DNA sequence of one of the clusters reveals six genes in the contiguous arrangement of H2B, H1, H3, H4, H2B and H2A. The order of genes within the second cluster is H3, H4, H2B and H2A. There is no evidence for the presence of an H1 gene in this cluster. Comparison of the three copepod H2B genes reveals a high degree of similarity between the 5' upstream regions and between the amino terminal halves of the two H2B genes found within the same cluster. From these data we infer that gene duplication and/or gene conversion events occurred within this cluster in the recent past. PMID- 1446075 TI - The nucleotide sequence of the human transcription factor HTF4a cDNA. AB - A partial cDNA has previously been isolated that encodes HTF4, a new member of the basic helix-loop-helix family of DNA binding proteins. We have reconstructed a full cDNA, designated HTF4a cDNA, which spans the entire HTF4 coding region. The 5' end of the reconstructed cDNA includes an open reading frame encoding a 117-residue polypeptide. Three closely spaced ATG codons in the major open reading frame may potentially serve as sites of initiation for HTF4a synthesis, to yield proteins that contain 682, 675, and 657 amino acid residues, respectively. Pairwise dot matrix analysis indicates that there are at least three distinct human genes which encode proteins related to the Drosophila daughterless. PMID- 1446076 TI - The nucleotide sequence between genes 31 and 30 of bacteriophage T4. AB - The nucleotide sequence of the 2994 bp T4 phage DNA fragment between genes 31 and 30 is presented. The fragment contains 7 complete open reading frames in the direction of early transcription and two early promoters, PE128.6 and PE128.2, which we show to cause difficulties in cloning DNA from this genomic region. Our data complete the nucleotide sequence and the organization of genes in the genomic region between T4 genes 31 and 30. PMID- 1446077 TI - Nucleotide sequence of bovine interleukin-6 cDNA. AB - We report the cloning of bovine interleukin-6 (IL-6) cDNA. The clone was isolated from a bovine-leukemia virus (BLV)-induced B cell-lymphosarcoma cDNA library cloned in the bacteriophage lambda gt11. The cDNA encodes a full length IL-6 protein made of 208 amino acids with 65, 53, 42 and 42% homology to published sequences of porcine, human, mouse and rat IL-6, respectively. The significance of IL-6 expression in a BLV-induced tumor is briefly discussed. PMID- 1446078 TI - Dysplasia, an ongoing controversy highlighted by objective measurements? PMID- 1446079 TI - Classification of autosomal dominant palmoplantar keratoderma: past-present future. PMID- 1446080 TI - Prognosing melanomas: the argyrophilic nucleolar organizer region approach. AB - Staining of argyrophilic nucleolar organizer regions (AgNORs) is a histological technique that has been assayed on a vast array of cutaneous tumors in order to help distinguish benign from malignant lesions. In a number of papers, malignant melanomas have been found to have a higher number of black nucleolar and extranucleolar dots (i.e. AgNORs) than benign nevi, including Spitz nevus. The technique may be used for prognostic purposes, as a recent paper suggests. Melanomas with more than 3.62 AgNORs/cell have a higher probability to develop metastasis than melanomas with fewer AgNORs. The problems such an apparently simple, fast and reproducible technique may pose are discussed in detail. PMID- 1446081 TI - L-tryptophan ingestion does not induce progressive systemic sclerosis (scleroderma). AB - A retrospective analysis of 153 patients suffering from progressive systemic sclerosis failed to show any correlation between either onset or worsening of the disease and L-tryptophan ingestion. Only one woman developed typical acrosclerosis without signs of the eosinophilia-myalgia syndrome during exposure to the drug. PMID- 1446082 TI - Staphylococcus aureus leukocidin: a new virulence factor in cutaneous infections? An epidemiological and experimental study. AB - Panton-Valentine leukocidin (PVL) is a Staphylococcus aureus (SA) exotoxin, which kills human granulocytes and monocytes in vitro. Among 43 SA strains from cutaneous infections, 12 were PVL producers, whereas among 49 blood culture strains, only 1 produced PVL. Most PVL-producing strains (11/22) came from 22 primitive cutaneous infections, especially furuncles and abscesses, while only 1 PVL-producing strain came from 21 secondary infections of dermatoses such as bullous or pruritic diseases. Intradermal injections of PVL in rabbits induced edema, erythema and necrosis; histopathological changes at the injection sites consisted mainly in leukocytoclasis and vascular necrosis. All changes were dose dependent, and previous immunization of rabbits partially neutralized PVL-induced effects. Production of PVL in vivo after injections of bacteria seems to be low, and the histopathological lesions induced in the rabbit skin do not appear to be specifically related to PVL activity. However, PVL is a good candidate as a new virulence factor in cutaneous SA infections. PMID- 1446083 TI - Extensive variant of cutaneous amyloidosis: report of a case with electron microscopic and immunohistochemical studies of the basement membrane zone at sites of amyloid production. AB - A 60-year-old Japanese female developed widespread lichenoid eruptions with pigmentation, which initially appeared in preceding erythematous skin lesions due to dermatomyositis. Thioflavine T and Dylon stainings, electron microscopy and immunohistochemistry revealed that thick amyloid deposits were present in the papillary dermis particularly beneath the epidermis. Autopsy showed no evidence of systemic amyloidosis. Electron microscopy of the lesional skin disclosed the disturbance of lamina densa formation in the epidermal basement membrane zone (BMZ). There was disruption and dissociation of the lamina densa from the basal cell, and a lamina-densa-like substance was found in the amyloid deposits. Immunofluorescence and immunoelectron microscopy showed that type IV and VII collagens, LDA-1 antigen (a noncollagenous component of the BMZ) and laminin were distributed in irregular thick deposits along the BMZ and were also present within the amyloid itself. These findings indicate that morphological and immunohistochemical abnormalities of the lamina densa may be involved in amyloid production at the interface of the epidermis and dermis, at least in this case. PMID- 1446084 TI - Derivation of a dysplasia index for epidermal neoplasia. AB - Measurements have been performed on histological sections of normal, paralesional and affected skin of patients with solar keratoses in an attempt at quantification of the degree of dysplasia. Features of dysplasia, including the epidermal thickness, the nuclear fraction and nuclear size distribution and shape, have been individually derived and incorporated into a formula designed to reflect the degree of dysplastic change within the epidermis. Application of this 'index of dysplasia' has been shown to differentiate lesional epidermis from that of the surrounding and normal non-sun-exposed skin. In addition, this index correlated well with independent dermatopathologists' assessments of the degree of dysplasia. PMID- 1446085 TI - Progressive facial hemiatrophy: report of five cases and biochemical analysis of connective tissue. AB - Five cases of progressive facial hemiatrophy (PFH) are reported. A nonindurated depression on normal-colored skin was observed in the cheeks of 3 subjects, and 2 patients showed indurated, pigmented atrophic lesions associated with linear scleroderma or generalized morphea. Lipoatrophy with mild subcutaneous fibrosis was observed histologically in the patients with nonindurated depressions. In contrast, the patients with indurated lesions exhibited a marked dermal fibrosis and the disappearance of appendices in the dermis. When compared with unaffected skin used as a control, collagen and glycosaminoglycan contents were not different in diseased areas. However, the dermatan sulfate/hyaluronic acid ratio was increased 1.5- to 3.2-fold in PFH patients regardless of their clinical and histological differences. These results suggest that both types of PFH may be based on a similar connective tissue disorder. PMID- 1446086 TI - Decreased peripheral blood eosinophil counts in severe psoriatic patients treated with low-dose cyclosporine A. AB - We report a clinical observation, a statistically significant decrease in peripheral blood eosinophils in patients treated with low-dose cyclosporine A for severe psoriasis 225/microliters at baseline to 114/microliters at week 12 (p = 0.04). We discuss the potential significance of this clinical finding. PMID- 1446087 TI - Palmoplantar orthokeratotic filiform hyperkeratosis in a patient with associated Darier's disease. Classification of filiform hyperkeratosis. AB - We present here the third published case of palmoplantar orthokeratotic filiform hyperkeratosis of particular clinical interest because of associated Darier's disease. We propose a classification of filiform hyperkeratosis in three groups on the basis of the topography (i.e. palmar and plantar, disseminated with palmoplantar sparing and linear) and the histology (i.e. porokeratosis or orthokeratosis) of the lesions. This keratinization disorder does not seem to be a specific disease entity but rather a syndrome secondary to various disorders. PMID- 1446088 TI - Inflammatory familial palmoplantar keratoderma: Greither's disease? AB - A case of a familial palmoplantar inflammatory keratoderma with autosomal dominant inheritance is reported. Associated clinical features included vasomotor troubles and hyperhidrosis consistent with a diagnosis of Greither's disease. Light microscopy was nonspecific. Electron microscopy showed aggregated tonofilaments around the nucleus, without true clumps. Desmosomes were numerous and cell-cell junctions showed an imbricated pattern, well demonstrated in the stratum corneum. The diagnosis of Greither's keratoderma is discussed. PMID- 1446089 TI - Coexistence of apparent transverse leukonychia (Muehrcke's lines type) and longitudinal melanonychia after 5-fluorouracil/adriamycin/cyclophosphamide chemotherapy. PMID- 1446090 TI - Perianal streptococcal cellulitis: treatment with topical mupirocin. PMID- 1446091 TI - Minocycline in granulomatous cheilitis: experience with 6 cases. PMID- 1446092 TI - A meta-analysis of studies carried out between 1946 and 1988 concerned with the efficacy of speech and language therapy treatment for aphasic patients. AB - An examination of the empirical evidence for the efficacy of speech and language therapy treatment for adult aphasic patients is undertaken with the aid of meta analysis which affords a statistical method of systematic data summary and synthesis. Patient characteristics and treatment outcomes are correlated to identify factors that contribute to the demonstration of a treatment effect. One of the most striking results of this retrospective study was the identification of the overwhelming failure to report data or include, in experimental controls, variables that might crucially affect outcome. PMID- 1446093 TI - Developmental verbal dyspraxia. I: A review and critique. AB - Developmental verbal dyspraxia is examined from four perspectives: clinical, phonetic, linguistic and cognitive. The paper critically discusses the problems encountered when criteria for identifying acquired speech disorders in the adult population are applied to children's speech difficulties without modifications. It is argued that studies of verbal dyspraxia in children have ignored the unfolding nature of this condition and that a developmental perspective has been lacking in the literature. A need for the inclusion of appropriate control groups and longitudinal case studies is identified. The issue and process of differential diagnosis are addressed and a checklist of criteria for identifying developmental verbal dyspraxia is included. It is noted that this process will inevitably be lengthy with data needed from different aspects of a child's development. Phonetic characteristics alone may not be sufficient to recognise this medical condition with its complex psycholinguistic and educational consequences. PMID- 1446094 TI - Developmental verbal dyspraxia. II: A developmental perspective on two case studies. AB - A longitudinal study of the speech errors of two school-age children with what was described as developmental verbal dyspraxia is presented. By comparing them with a group of normally developing children matched on articulation age, it was possible to identify speech errors not typical of earlier speech development, involving problems with syllable structure planning and vocal tract coordination. The speech-disordered children could produce more words correctly than the controls, but, when they did make speech errors, these were more serious than those found in the younger children. The speech-disordered children were followed up 4 years later. Although their speech had improved, they presented with the same profile of error types. They had increased intelligibility by adding more word-specific articulations but still had difficulties with novel and complex material. The adoption of a developmental framework in this study allowed the identification of different levels of breakdown within the speech production process. The case-study method is recommended to investigate how these levels may interact and the clinical implications of the findings are outlined. PMID- 1446095 TI - The predictive validity and accuracy of a screening test for language delay and auditory perceptual disorder. AB - Infants (321) who had been screened for language delay and auditory perceptual problems at 9 months of age were evaluated 1 year later. Of these infants 88.6% were correctly classified as at-risk or not-at-risk of delayed linguistic development. The correlation between performance on the screen and on a language scale was 0.49. The great majority of those with receptive and expressive delay continued to show problems at 2 years of age, whereas half of those with expressive delay alone were within normal limits. No evidence was found that a history of fluctuating hearing loss contributed to the development of either language delay or auditory perceptual problems. PMID- 1446096 TI - The communication abilities of 2- to 4-year-old twins. AB - The speech and language abilities of pre-school multiple-birth children (MBC) are often reported to be impaired. In this study, teh syntactic, semantic, pragmatic, articulation and phonological skills of 19 sets of MBC were assessed. The comparisons made were between MBC and matched singleton controls, between siblings within multiple-birth sets, and for each multiple-birth child with different conversational partners (sibling versus speech and language therapist). The results indicated that the MBC performed more poorly than the singleton controls on measures of syntax and phonology. Whilst there were quantitative and qualitative similarities between siblings' linguistic abilities, their phonologies were not identical, and the MBC's speech and language changed with different conversational partners. The implications of the results for the existence of 'twin language', choice of language sample for assessment of functional communication and the need for preventive intervention programmes are discussed. PMID- 1446097 TI - Speech control in persistent tardive dyskinesia: a case study. PMID- 1446098 TI - A simple nasal anemometer for clinical purposes. AB - There is a need for clinical methods which give more direct information about the behaviour of the velopharyngeal mechanism in natural speech than do the examination methods normally applied to patients suffering from velopharyngeal insufficiency. One possibility is the recording of nasal airflow in order to detect nasal emission of air. The purpose of the present study is to examine the qualities and the characteristics of a simple and cheap nasal anemometer. As this type of flowmeter is considered less reliable than most other flowmeters, its limitations must be clearly understood and accounted for in drawing conclusions. Therefore, nasal airflow in speech obtained with this flowmeter is discussed in relation to nasal airflow obtained by the more reliable pneumotachograph and in relation to nasal airflow data found in the literature. The tests made here suggest that, at least for the type of speech material and measurements used in the present study, reliable nasal airflow data can be obtained by the anemometer. PMID- 1446099 TI - Can the Lombard effect be used to improve low voice intensity in Parkinson's disease? AB - Low voice intensity is a common problem in Parkinson's disease. It is typically resistant to drug therapy and often persists despite extensive behavioural speech and language therapy. Based on previous findings that masking noise will produce a consistent increase in voice intensity in most normal individuals, the effects of white masking noise, presented at a sound pressure level of 90 dB, was examined in 10 parkinsonian patients with low voice intensity. Results indicated that all Parkinson's disease patients showed a marked increase in their voice intensity. Given this finding, it is proposed that masking noise may be an effective treatment for reduced voice intensity in parkinsonian speakers, particularly with the future adaptation of portable voice-activated maskers, such as the Edinburgh Masker. PMID- 1446100 TI - Vocal attrition related to idiosyncratic dysphonia: re-analysis of survey data. AB - In a recent survey study it was found that female army instructors were significantly more likely to suffer from symptoms of vocal attrition than new female recruits, supporting the clinical impression that those who are engaged in a vocally taxing vocation are at higher risk for vocal attrition than those who are not. In the present study we found that instructors who reported having rapid, excessive or loud speech, or a combination of these, were significantly more likely to report symptoms of vocal attrition than instructors who reported not having these speech habits. Difference in prevalence of vocal attrition symptoms among recruits with and without these speech habits was statistically non-significant. The present findings confirm the clinical impression that idiosyncratic dysphonia can increase the risk of vocal attrition, especially in people who are engaged in a vocally demanding profession or vocation. PMID- 1446101 TI - An evaluation study of voice therapy in non-organic dysphonia. AB - Thirty patients diagnosed as suffering from non-organic dysphonia were assigned to one of three treatment groups: direct therapy, indirect and no treatment for a period of 8 weeks. Therapeutic outcome was evaluated by independent judges, patient self-evaluation, electrolaryngograph ratings and measures of fundamental frequency. The direct treatment group showed the most significant improvement in the return to normal voice functioning followed by the indirect treatment group. One patient in the control group showed improvement without any intervention. This study provides evidence in support of the effectiveness of both direct and indirect therapy in the treatment of non-organic dysphonia and raises questions concerning individual patient responses to these approaches. PMID- 1446102 TI - A survey of the communication-impaired population of Tayside. AB - There are few published surveys that are designed specifically to describe the total population of clients with communication disorders who might potentially benefit from the use of a communication aid. Such data, however, would be useful in planning the funding and staffing of rehabilitation services in a region. Figures are also needed to identify populations whose needs are currently not being met and thus to establish areas of future developments both for service and research purposes. The survey reported here was carried out as part of a project concerned with the provision of augmentative communication to the neurologically impaired child and young adult. It was intended to produce a broad description of the communication-impaired population in Tayside. The survey was then used to identify detailed information about clients who may benefit from using a communication aid, and it also highlighted some provision and research issues. Access to communication aids for the non-speaking population was found to have been restricted by lack of funding, resources and opportunities for training for therapists in the use of augmentative and alternative communication. Future research and development should particularly address the needs of the aphasic population whose needs were not found to be met by currently available communication aids. PMID- 1446103 TI - Metalinguistic awareness of nuclear accent and of compound stress in an 8 year old. PMID- 1446104 TI - JMRI 1933: where to now? PMID- 1446105 TI - Routine quantitative analysis of brain and cerebrospinal fluid spaces with MR imaging. AB - A computerized system for processing spin-echo magnetic resonance (MR) imaging data was implemented to estimate whole brain (gray and white matter) and cerebrospinal fluid volumes and to display three-dimensional surface reconstructions of specified tissue classes. The techniques were evaluated by assessing the radiometric variability of MR volume data and by comparing automated and manual procedures for measuring tissue volumes. Results showed (a) the homogeneity of the MR data and (b) that automated techniques were consistently superior to manual techniques. Both techniques, however, were affected by the complexity of the structure, with simpler structures (eg, the intracranial cavity) showing less variability and better spatial correlation of segmentation results between raters. Moreover, the automated techniques were completed for whole brain in a fraction of the time required to complete the equivalent segmentation manually. Additional evaluations included interrater reliability and an evaluation that included longitudinal measurement, in which one subject was imaged sequentially 24 times, with reliability computed from data collected by three raters over 1 year. Results showed good reliability for the automated segmentation procedures. PMID- 1446106 TI - Phase-contrast MR angiography of vascular malformations of the spinal cord at 0.5 T. AB - Preliminary experience with phase-contrast magnetic resonance (MR) angiography at 0.5 T applied in 12 cases of vascular malformations of the spinal cord is reported. There were six intramedullary arteriovenous malformations (AVMs), four perimedullary fistulas, and two dural arteriovenous fistulas with perimedullary drainage, all proved with x-ray angiography. The small size of the vessels and their location within a bony structure presented a technical challenge. Serpentine vascular signal patterns were identified within the spinal canal in all cases, showing good correlation with the x-ray angiographic pattern. Relative to spin-echo images, MR angiograms allowed better visualization of the venous drainage. The nidus of intramedullary AVMs was more difficult to recognize. The ability to manipulate the velocity-encoding value allows better characterization of flow speed. The results underline the two dimensions of the phase-contrast technique, which provides both anatomic images and dynamic information about vascular malformations. MR angiography does not replace selective x-ray angiography, which is indispensable for therapeutic strategy (endovascular procedure or surgery), but it can be considered a valuable alternative to x-ray angiography during follow-up. PMID- 1446107 TI - MR angiography with a cardiac-phase--specific acquisition window. AB - A method for cardiac-phase-specific magnetic resonance (MR) angiography is presented. An electronics module permits incrementing of phase-encoding gradients and storage of incoming data only during a chosen portion of the cardiac cycle. Suppression of stationary material is maintained by delivering radio-frequency pulses at constant TR throughout the cycle. Imaging of a pulsatile flow phantom demonstrates that acquiring data only during systole substantially increases the signal intensity of flowing material. In addition, phase-encoding ghost artifacts are eliminated from the neighborhood of the vessel. Image acquisition time is minimized by acquiring only the low-frequency phase-encoding lines in the cardiac phase-specific mode. In healthy volunteers, greatly improved MR angiograms of the lower extremities are obtained. Fat saturation and magnetization transfer further enhance vessel/background contrast. Acquiring data only during systole ensures rapid inflow for all phase-encoding lines, permitting a near-longitudinal section orientation without in-plane saturation. This substantially reduces total acquisition time relative to axial acquisition. PMID- 1446108 TI - Correlation of MR changes with Doppler US measurements of blood flow in exercising normal muscle. AB - Muscle data from phosphorus-31 magnetic resonance (MR) spectroscopy and hydrogen 1 MR imaging and popliteal artery data from duplex Doppler ultrasound were compared during an exercise test of the anterior compartment of the leg, in nine healthy volunteers. Significant variations (mean +/- standard deviation) were observed at the end of exercise versus rest in intracellular pH (pHi) (6.32 +/- 0.02 vs 7.02 +/- 0.04, P < .001), T2 (38.2 msec +/- 2.3 vs 29.5 msec +/- 1.1, P < .001), and popliteal output (652 mL/min +/- 232 vs 149 mL/min +/- 65, P < .001). These variables showed the following significant correlations at the end of exercise: T2 and pHi (r = -.784, P < .01), T2 and popliteal output (r = .737, P < .03), and pHi and popliteal output (r = -.902, P < .001). However, during recovery, the T2 curve was significantly different from those of pHi and popliteal output. This suggests that even if circulatory conditions play a role in the maximum T2 variation during exercise, they do not directly explain T2 changes. Furthermore, the correlations involving pHi suggest the role of the metabolism of exercising muscle in transcapillary fluid movement. PMID- 1446109 TI - Magnetization-prepared MR angiography with fat suppression and venous saturation. AB - Magnetization-prepared magnetic resonance (MR) angiography (MPMRA) is an inflow based two-dimensional (2D) imaging sequence in which a preparation phase precedes rapid image acquisition. For maximal blood/tissue contrast, an inversion-recovery preparation nulls signal from static tissue. If needed, a second inversion suppresses signal from fat. Fully magnetized blood flows in after the inversion pulse(s), providing high signal intensity. The centric phase-encoding order, which ensures that the initial contrast is reflected in the image set, requires the use of a modified venous saturation technique. The sequence is described and its performance assessed with regard to (a) depiction of in-plane flow, (b) fat suppression, and (c) venous saturation. Phantom and volunteer studies showed good performance in all three areas. MPMRA images, acquired in just 2-4 seconds per image, had a blood/tissue contrast-to-noise ratio nearly twice that of standard 2D time-of-flight MR angiograms, acquired in 5-7 seconds. The technique is promising for restless patients and in anatomic areas plagued by motion degradation. PMID- 1446110 TI - Effects of acceleration on the accuracy of MR phase velocity measurements. AB - Acceleration in blood flow can affect the accuracy of phase velocity measurements. Convective acceleration is due to changes in flow geometry and is independent of the time-varying acceleration caused by flow pulsatility. To analyze the effects of convective acceleration on flow velocity measurements, phase velocity measurements were obtained in steady laminar flow in the convergent segment of a 90%, hourglass-shaped stenosis phantom at a Reynolds number of 1,500. Measurements at the stenosis indicated that convective acceleration caused the measured values of average cross-sectional velocity to deviate as much as 37% from the theoretical values. The magnitude of the error could be accounted for by including the convective acceleration term in the phase shift equation. Convective acceleration effects should not be ignored in flow velocity measurements through stenoses, even when time-dependent acceleration due to flow pulsatility can be neglected. PMID- 1446111 TI - MR imaging-histopathologic correlation of thermal injuries induced with interstitial Nd:YAG laser irradiation in the chronic model. AB - Magnetic resonance (MR) imaging-histopathologic correlation of thermal injuries induced with interstitial laser irradiation was performed in a chronic model up to 12 weeks after laser exposure. T2-weighted MR images showed irreversible coagulative necrosis as a low-signal-intensity area. A higher-intensity surrounding area, corresponding to edema, was also present in acute lesions on T2 weighted images. Serial studies of the chronic model showed that a substantial portion of the interstitial edema zone progressed to coagulative necrosis up to 7 days after laser irradiation. This necrotic zone decreased in size beyond 2 weeks, presumably through biologic healing. MR imaging and pathologic findings correlated well in the chronic model. MR imaging has the potential to depict acute, irreversible thermal damage even before morphologic change is seen at the standard pathologic examination. Recognizing the dynamics of tissue response to interstitial laser irradiation on MR images is valuable for estimation of true lesion volume. PMID- 1446112 TI - Dynamic image reconstruction: MR movies from motion ghosts. AB - It has been previously shown that an image with motion ghost artifacts can be decomposed into a ghost mask superimposed over a ghost-free image. The present study demonstrates that the ghost components carry useful dynamic information and should not be discarded. Specifically, ghosts of different orders indicate the intensity and phase of the corresponding harmonics contained in the quasi periodically varying spin-density distribution. A summation of the ghosts weighted by appropriate temporal phase factors can give a time-dependent dynamic image that is a movie of the object motion. This dynamic image reconstruction technique does not necessarily require monitoring of the motion and thus is easy to implement and operate. It also has a shorter imaging time than point-by-point imaging of temporal variation, because the periodic motion is more efficiently sampled with a limited number of harmonics recorded in the motion ghosts. This technique was tested in both moving phantoms and volunteers. It is believed to be useful for dynamic imaging of time-varying anatomic structures, such as in the cardiovascular system. PMID- 1446113 TI - Altered phase-encoding order for reduced sensitivity to motion in three dimensional MR imaging. AB - A method of reordering phase and slab encoding that can be used to address some of the inherent problems due to motion in three dimensional imaging is described and implemented. The method is shown to be more robust with respect to reducing artifacts resulting from several fundamental types of motion. It can be readily implemented on a standard magnetic resonance imager with essentially no increase in total imaging time. Results of simulations and phantom and in vivo experiments are presented. PMID- 1446114 TI - Correlation of MR imaging and histologic findings in mouse melanoma. AB - M2R melanoma tumors in male C57 black mice were used to correlate magnetic resonance (MR) images with the corresponding histologic slices and to determine if analysis of the achievable correlation can provide a basis for predicting gross histologic features with MR imaging alone. The MR imaging sections obtained at 4.7 T were each 680 microns thick, with an in-plane resolution of 195 microns. The distribution of melanin within the histologic slices correlated well with the high-signal-intensity regions on the T1-weighted images (T1WIs), while these regions had low signal intensity on the T2-weighted images (T2WIs), providing evidence that melanin or melanin-associated paramagnetic species are responsible for the observed proton relaxation rate enhancement. Viable melanoma cells typically showed intermediate signal intensity on T2WIs, T1WIs, and proton density images. Necrosis typically had high signal intensity on T2WIs, T1WIs, and proton-density images. Quantitation of the MR imaging results, followed by statistical analysis, demonstrated statistically significant differences between melanin-rich, viable-melanoma, and necrotic regions on MR images. PMID- 1446115 TI - MR imaging with spatially variable resolution. AB - In some situations it may be advantageous to produce "locally focused" magnetic resonance images that have nonuniform spatial resolution matching the expected local rate of spatial variation in the object. Because such an image has fewer pixels than a conventional image with uniformly high resolution, it can be reconstructed from fewer signals, acquired in less time. This can be done by using a highly convergent representation of the image as a sum of orthonormal functions with slow (fast) spatial variation in relatively homogeneous (heterogeneous) parts of the object. Since this series is shorter than a conventional truncated Fourier series, its terms can be calculated from a subset of the usual array of phase-encoded signals. The optimal choice of these phase encodings, which are usually scattered nonuniformly in k space, results in minimization of noise in the reconstructed image. The technique is illustrated by applying it to simulated data and to data from images of phantoms. PMID- 1446116 TI - Cardiac metabolism in patients with dilated and hypertrophic cardiomyopathy: assessment with proton-decoupled P-31 MR spectroscopy. AB - Proton-decoupled phosphorus-31 heart spectroscopy was performed in healthy subjects (n = 9) and patients with dilated cardiomyopathy (DCM, n = 9) or hypertrophic cardiomyopathy (HCM, n = 8). The phosphocreatine (PCr)-to-adenosine triphosphate ratio (+/- one standard deviation) after correction for blood contribution and partial saturation was significantly lower in HCM patients relative to the control subjects (1.32 +/- 0.29 vs 1.65 +/- 0.26, P < .05) but not in DCM patients (1.52 +/- 0.58 vs 1.65 +/- 0.26). The inorganic phosphate (Pi) peak was resolved only in patients with the highest spectral quality. Myocardial pH was lower in HCM patients (n = 6) relative to control subjects (n = 4) (7.07 +/- 0.07 vs 7.15 +/- 0.03, P < .05). The Pi/PCr ratio was higher in DCM (n = 3) and HCM (n = 6) patients relative to control subjects (n = 4) (0.29 +/- 0.06 and 0.20 +/- 0.04, respectively, vs 0.14 +/- 0.06; P < .05). Elevated phosphodiester signal in DCM patients correlated with 2,3-diphosphoglycerate signal (r = .94), reflecting blood pool contamination. P-31 spectroscopy enabled detection of abnormalities in cardiac metabolism and determination of pH in patients with HCM and DCM. PMID- 1446117 TI - Does memory loss occur after MR imaging? AB - In four separate studies, the existence of specific memory loss after magnetic resonance (MR) imaging at 1.5 T was assessed by means of recognition and recall tests for faces, common objects, lexical items, and by digit span, in a pre-post paradigm. Although specific memory loss was demonstrated, it was shown that the loss was not due to the main magnetic field of the imager or to radio-frequency pulse sequences, but rather to probable psychological (not physical) factors. No gross or subtle memory changes could be attributed to MR imaging, because control groups showed similar patterns of memory loss. PMID- 1446118 TI - Laryngospasm after administration of gadopentetate dimeglumine. AB - Few serious adverse reactions associated with the use of gadopentetate dimeglumine in magnetic resonance imaging have been reported. The present case involves an 8-year-old girl who developed laryngospasm after administration of gadopentetate dimeglumine. PMID- 1446119 TI - Lumbar myelography with three-dimensional MR imaging. AB - A strongly T2*-weighted, three-dimensional (3D) PSIF (time-reversed FISP [fast imaging with steady-state precession]) gradient-echo magnetic resonance (MR) sequence, with postprocessing of the 3D data set with a maximum-intensity projection (MIP) algorithm, produced x-ray myelography-equivalent images. The method was tested in 10 healthy volunteers to optimize sequence parameters and was evaluated in 30 patients with proven lumbar disk disease. MIP myelograms, unlike two-dimensional MR images, could not show the pathologic disks themselves but clearly demonstrated the effect on the thecal sac, giving a clear overall view of its geometry and dimensions, especially when displayed in a cine loop. All 28 medial and mediolateral disk herniations could be visualized, whereas only three of eight intraforminal disk herniations were seen on MR myelograms. PMID- 1446120 TI - Occupational radiation exposure to interventional radiologists: a prospective study. AB - This study investigates the occupational radiation dose to interventional radiologists and the operator-controlled factors that may affect dose. Thirty interventional radiologists wore radiation badges over and under lead aprons for 2 months and answered a questionnaire. The relationships between dose and caseload, case mix, experience, optional fluoroscopy features, lead apron type, and additional lead shielding were evaluated. Mean projected yearly dose (PYD) over lead was 49.1 mSv (1 mSv = 100 mrem) but was 66.6 mSv for persons performing 1,000 or more cases per year (P = .027). Mean PYD under lead was 0.9 mSv but was 1.3 mSv for persons with 0.5-mm lead coverage and 0.4 mSv for those with 1.0-mm lead coverage (P = .002). No other significant correlation was found. Conclusions are that caseload and apron thickness are the primary determinants of total body dose, that over-lead dose is high enough to warrant additional lead shielding for the head and neck, and that a double-thickness apron lowers under-lead dose by two-thirds. The large difference between under-lead and over-lead doses suggests that use of a collar badge alone for monitoring purposes is not predictive of total-body effective dose for this group of radiation workers. PMID- 1446121 TI - Life tables for clinical scientists. AB - The life-table, or Cutler-Ederer, method of survival analysis is a simple and efficient means of estimating the probability that the first instance of an event will occur in a given period of time in studies complicated by incomplete patient follow-up. This discussion is designed to acquaint the nonstatistician with the general concepts, assumptions, advantages, and disadvantages of life-table analysis. The arcane nature of the calculations frustrates attempts at simplification. A glossary of statistical terms and sample calculations are provided for interested readers. PMID- 1446122 TI - JVIR after Andrew. PMID- 1446123 TI - Long-term results of angioplasty in 110 patients with renal artery stenosis. AB - Percutaneous transluminal renal angioplasty (PTRA) is generally considered of little benefit in the treatment of ostial renal artery stenosis. This report contains long-term follow-up (> 12 months in all patients; mean follow-up, 38 months) for 110 patients who underwent PTRA for treatment of ostial renal artery stenosis. There was no significant difference in patient benefit related to bilaterality or multiplicity of lesions treated or to renal function before angioplasty (P > .1). Although there was no statistically significant difference in benefit among groups of patients who received treatment, certain trends were apparent. The least benefit occurred in patients with insulin-dependent diabetes and those with symptoms or history of vascular disease in another organ system. Treatment of lesions with proportionately larger balloons did not result in greater benefit. Restenoses were redilated in 16 patients for whom initial treatment failed. Eleven of these were ostial restenoses. The ostial stenosis in one patient was redilated a second time. At the end of follow-up, primary, secondary, and tertiary clinical benefits were 48%, 57%, and 58%, respectively. This was not statistically different (P = .14) from a control group of 94 patients with nonostial stenoses who had 68% long-term benefit. The authors conclude that ostial renal artery stenosis is not a contraindication to PTRA, and balloon angioplasty can play an important role in blood pressure control in this patient population. PMID- 1446124 TI - Prolonged binding of radiolabeled recombinant tissue-type plasminogen activator after angioplasty and enclosed thrombolysis of the femoropopliteal arteries. AB - The authors measured the binding of indium-111-labeled recombinant tissue-type plasminogen activator (rt-PA) within the recanalized femoropopliteal segment after percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis. In patients with long occlusions (n = 3), 91 micrograms of rt-PA was bound 1 hour after the procedure, and the half-time of the final washout curve averaged 114 hours. After PTA in patients with multiple stenoses (n = 6), 45 micrograms of rt PA was bound, and the half-time averaged 32 hours. These values were significantly smaller than those in patients with occlusions (P < .01). In patients with a single stenosis (n = 4), 19 micrograms of rt-PA was bound, and the half-time averaged 5 hours. These values were significantly smaller than those in patients with multiple stenoses (P < .01). The progressive accumulation of rt-PA at the sites of PTA therapy is most likely related to increasing presence of fibrin with increasing lesion severity. Fibrin accumulation may be partly responsible for early failures after PTA in extensive lesions. Removal of this fibrin with enclosed thrombolysis might improve patency. PMID- 1446125 TI - Arterial embolization as definitive treatment for benign insulinoma of the pancreas. PMID- 1446126 TI - Preoperative embolization of the spleen in children with hypersplenism. AB - Splenomegaly associated with myelodysplastic disorders in children may be massive and can result in pancytopenia, abdominal discomfort, and respiratory distress. When these symptoms cannot be relieved by nonsurgical means, splenectomy may be indicated. Under such conditions, surgical splenectomy carries increased risks, as the thrombocytopenia is difficult to correct secondary to splenic sequestration. Additionally, the surgical anatomy is often distorted secondary to the massive spleen and dissection can be difficult. These factors can lead to uncontrollable hemorrhage. In an attempt to decrease intraoperative blood loss, the authors successfully performed preoperative splenic artery embolization in 11 of 12 children (age range, 1-11 years) with pancytopenia due to hypersplenism. Hypersplenism requiring surgical splenectomy was due to leukemia (n = 9), myelodysplastic syndrome (n = 1), immune thrombocytopenia (n = 1), and osteopetrosis (n = 1). Embolization was performed under general anesthesia, prior to surgery, with gelatin sponge particles alone, Gianturco coils alone, or a combination of polyvinyl alcohol sponge particles and Gianturco coils. Embolization allowed for safe surgical splenectomy. PMID- 1446127 TI - Direct aneurysm puncture and coil occlusion: a new approach to peripancreatic arterial pseudoaneurysms. AB - A patient with pancreatitis complicated by a pseudoaneurysm in the pancreatic head was treated with a radiologic-surgical approach. At surgery, the phlegmon was exposed and treated by means of direct puncture and embolization with Gianturco coils under color Doppler flow imaging guidance. PMID- 1446128 TI - Fluoroscopically guided percutaneous gastrostomy in children. AB - Percutaneous gastrostomy was performed in 27 patients with ages ranging from 7 months to 18 years (mean, 8 years). Patient weights ranged from 4.7 to 73 kg (mean, 25 kg). Access to the stomach was planned and achieved with only fluoroscopic guidance. The technical success rate was 100%. Major procedure related complications including death, sepsis, hemorrhage, peritonitis, or early tube removal did not occur. The minor complication of local skin infection occurred in six patients. Twenty-six patients (96%) tolerated tube feedings well. Mean follow-up was 184 days, and median follow-up was 103 days. At 30 days, 26 patients (96%) were alive. Percutaneous gastrostomy under fluoroscopic guidance is a safe and effective method of obtaining long-term nonparenteral nutritional access in pediatric patients. PMID- 1446129 TI - Percutaneous gastrostomy and gastrojejunostomy after gastric surgery. AB - The authors reviewed their experience with percutaneous gastrostomy and gastrojejunostomy in 30 consecutive patients who had undergone prior gastric surgery consisting of either partial resections (n = 24) or alteration of normal gastric anatomy (n = 6). Parameters evaluated included indications for the procedure, procedural modifications, type of prior gastric surgery, major and minor procedural complications, tube efficacy, and follow-up data. Gastrostomy tubes were placed in 27 patients for enteral feeding and in three for decompression. The success rate (100%), as well as the prevalence of major (0%) and minor (23%) morbidity--transient fever, skin infection, and high gastric residuals--were similar to those reported in patients who had not undergone prior gastric surgery. Thirty-day mortality was 13% (four patients); no deaths were related to the gastrostomy tube placement. Minor procedural modifications such as an extra-long needle, a peel-away sheath, or additional rotational fluoroscopy were necessary in 18 patients (60%). Knowledge of the postsurgical gastric anatomy is crucial in this subset of patients. Prior gastric surgery is no longer a contraindication to percutaneous gastrostomy or gastrojejunostomy tube placement. PMID- 1446130 TI - Passive blood/contrast agent exchange in angiographic catheters and its effects on platelets. AB - A static column of contrast agent or saline in an angiographic catheter will passively exchange with blood during angiography. The authors investigated the time course of this exchange in 5.5- and 7-F polyethylene catheters inclined at various angles. Passive blood exchange occurred 2 cm into the catheters within 7 15 seconds at most catheter tip angles, except for those catheters oriented so that their tips were nearly horizontal. In a separate series of experiments, the effect of contrast agent on platelet function and blood clotting was analyzed. The agent was sufficiently diluted in blood so as to simulate an angiographic procedure. The studies were performed in 60 cylindrical polyethylene containers with both unheparinized and heparinized blood. Use of an ionic contrast agent, more than a nonionic agent, lengthened the time for platelet aggregation (mean increases for ionic vs nonionic agents were 46.4 and 37.1 seconds, for unheparinized and heparinized blood, respectively), platelet adhesion to polyethylene surfaces (mean increases, 46.0 and 64.2 seconds), and platelet stimulated coagulation (mean increases, 38.5 and 43.9 seconds). Conventional, intermittent flushing with saline or filling the catheter with contrast agent may be insufficient to prevent blood from rapidly back-filling the catheter tips. Contrast agents (ionic more than nonionic) distributed in the patient's blood volume inhibit platelet coating of catheter lumens and/or blood clotting under such circumstances. PMID- 1446131 TI - Optimal central trapping (OPCETRA) vena caval filter: results of experimental studies. AB - The authors present the in vitro and in vivo results of use of a new vena caval filter, the optimal central trapping (OPCETRA) filter. The in vitro study was designed to compare the clot-trapping effectiveness of three filters: the OPCETRA, the stainless steel Greenfield, and the original Vena Tech-LGM. Standardized 3-mm, 5-mm, and 7-mm clots were captured in 66%, 100%, and 100% of cases, respectively, with the OPCETRA filter; in 34%, 82%, and 100% of cases with the Greenfield filter; and in 50%, 100%, and 100% of cases with the LGM filter. When filters were tilted 15 degrees, 100% of the 5-mm clots were trapped with the OPCETRA filter versus 50% with the Greenfield (P < 1.04 x 10(-9)) and 70% with the LGM (P < 1.78 x 10(-5)) filters. The in vivo animal study was designed to confirm ease of placement, tolerance, and effectiveness of the OPCETRA filter in sheep. Animals were separated into two groups: Group 1 underwent embolization through the femoral vein 40 days after filter implantation and were killed immediately; group 2 underwent embolization at 90 days and were killed 8 days later. In all cases pathologic analysis on the vena cava wall was performed after resection. The in vivo study demonstrated no tilting or migration with the OPCETRA filter. These encouraging results can be explained by the filter's hourglass shape, the number of arms, and the slow release of the filter at insertion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446132 TI - Transvenous retrieval of misplaced stainless steel Greenfield filters. AB - Transvenous retrieval was attempted in five patients following surgical misplacement of stainless steel Greenfield filters. Four filters were located within the right atrium, and one was in the left hepatic vein. All retrievals were attempted within 5 days of placement. Retrieval was successful for the four filters in the right atrium and failed for the filter in the left hepatic vein. One air embolism occurred; this was the only filter- or retrieval-related complication. Transvenous retrieval is a safe and effective minimally invasive method of removing misplaced filters. PMID- 1446133 TI - Placement of dual bird's nest filters in an unusual case of duplicated inferior vena cava. AB - The authors describe an unusual variant of inferior vena cava duplication, with azygos continuation of the right vena cava and hemiazygos continuation of the left vena cava, discovered at cavography in a patient with pulmonary embolism. Following unsuccessful attempts to advance titanium Greenfield filters through tortuous iliac veins, bilateral Bird's Nest filters were placed successfully. PMID- 1446134 TI - Injection characteristics and downstream contrast material distribution of flush aortography catheters: in vitro study. AB - Performance of 11 commercially available 4- and 5-F aortic flush catheters was evaluated with respect to the extent of upstream injection, catheter motion, and downstream homogeneity of a 10-, 15-, and 20-mL/sec bolus of 76% meglumine sodium diatrizoate at room temperature. Tests were made in a pulsatile aortic flow model containing circulating fluid isoviscous to blood. The injection process was recorded on videotape. Homogeneity of the contrast material bolus was determined spectrophotometrically from samples collected from the center and each of the four quadrants of the vessel lumen. Upstream contrast material injection between 1.5 and 7 cm in length emerged from all catheters; it was lowest with one of the "tennis racket" designs from one and a new spiral end-loop design (Halo) from another manufacturer. All catheters, except the most rigid and largest-caliber catheter (5.8 F) showed considerable shaft motion at the higher injection rates. Downstream contrast material mixing homogeneity was always best at the highest injection rate but altogether was better for the Halo catheter than for any other catheter tested. It is concluded that all tested 4- and 5-F aortic flush catheters show some undesirable features, but certain design modifications improve performance and comparative testing is helpful to distinguish such features. PMID- 1446135 TI - Arteriography for proximity of injury in penetrating extremity trauma. AB - Arteriography for proximity of injury was studied prospectively at a trauma center. Findings in 85 patients with penetrating extremity wounds were analyzed to determine the prevalence and types of vascular abnormalities seen with these injuries. Ninety-two limb segments were studied for 77 gunshot and 15 stab wounds. Arteriographic findings were positive in 24% overall but in only 5% for injuries confined to major vessels. A 60% positive rate was seen in a small subgroup of 10 patients with fractures due to gunshot wounds. The most frequently injured vessels were muscular branches of the deep femoral artery (59%); the most common injury was focal, non-occlusive spasm (42%). All patients were treated conservatively, without sequelae at follow-up. In this study, the vascular injuries found at arteriography for proximity of injury in penetrating trauma due to bullets of knives, particularly in the thigh, did not require surgical or radiologic intervention. PMID- 1446136 TI - Use of localizing wires for pulmonary nodules. PMID- 1446137 TI - Treatment of aneurysms with compression: historical perspective. PMID- 1446138 TI - The effects of intraluminal and extraluminal drug application on secretion and smooth muscle tone in the ferret liquid-filled trachea in vitro. AB - With the ferret liquid-filled trachea in vitro, intraluminal methacholine (MCh), phenylephrine (PE) and histamine (Hist) increased smooth muscle tone and salbutamol (Salb) decreased tone. Lysozyme output was increased by intraluminal MCh and PE. Albumin transport into the lumen was not altered by intraluminal Hist, Salb or PE. The concentration-response curves for smooth muscle contraction and for lysozyme output to extraluminal MCh lay to the left of those for intraluminal MCh. Indomethacin shifted the smooth-muscle response curves to MCh significantly to the left but did not significantly alter lysozyme output. Extraluminal MCh produced a concentration-dependent increase in albumin output whilst intraluminal MCh did so in one of three studies. Albumin output in response to MCh was not significantly altered by indomethacin. Thus, MCh has a less potent effect on smooth muscle and lysozyme secretion and, to a lesser extent, on epithelial albumin transport when given intraluminally. This may be because the epithelium restricts diffusion of the drug or due to the production of a non-prostanoid factor which inhibits smooth muscle responsiveness. Smooth muscle responsiveness is enhanced by blocking cyclooxygenase activity, suggesting MCh-induced release of a prostanoid with relaxant activity. PMID- 1446139 TI - Localization of immunoreactive endothelin and proendothelin in the human lung. AB - The endothelins are a family of three 21-amino-acid peptides: endothelin-1, endothelin-2 and endothelin-3. They are powerfully vasoactive, causing both contraction and relaxation of blood vessels. They are also active in the lung causing long lasting bronchoconstriction. Antibodies were raised in rabbits against the C-terminal heptapeptide of endothelin-1 (endothelin-1(15-21)) and to portions of the C-terminus of the human proendothelin-1(31-38), proendothelin 2(31-37) and proendothelin-3(31-41 amide) and tested by enzyme-linked immunosorbent assay to determine their titre and cross-reactivity. We used these antibodies to determine the localization of mature endothelin in the adult human lung and to determine the distribution of each of the three proendothelins. Mature endothelin immunoreactivity was present in airway epithelia and submucosal glands throughout the lung. In the airway epithelia immunoreactive proendothelin 1 and proendothelin-3 were detected, while immunoreactivity of all three isoforms was present in submucosal glands. Quantitative in vitro receptor autoradiography was used to locate specific endothelin binding sites. The rank order for density of endothelin binding site occurrence was: lung parenchyma greater than airway smooth muscle greater than airway epithelia. If immunoreactive endothelin is released onto these sites in vivo, endothelin may act as a paracrine mediator in the human lung. PMID- 1446140 TI - An in vivo preparation for measurement of plasma protein and lysozyme output in the ferret tracheal lumen. AB - An in-vivo ferret tracheal preparation has been developed to study the appearance in the liquid-filled trachea of fluorescein-labelled plasma proteins (FLP) and of lysozyme from submucosal gland serous cells. In order to investigate the influence of nervous activity on the appearance of FLP and lysozyme in the tracheal lumen, the effects of intraluminal bradykinin (an inflammatory mediator and sensory nerve stimulant), intraluminal capsaicin (a stimulant of C-fibres) and electrical stimulation of the cut peripheral end of the right cervical vagus nerve have been measured. Vagal stimulation (10 V, 10 Hz, 1 ms, 90-120 s) increased the secretory rate of lysozyme. It had no effect on FLP rate of output. Intraluminal bradykinin (100 microM) produced a small but significant increase in FLP output but had no effect on lysozyme secretion. Intraluminal capsaicin (33 microM) had no effect on FLP output and had variable effects on lysozyme output. Tracheal pressure was increased by vagal stimulation but was unaffected by bradykinin and capsaicin. Thus, bradykinin increases plasma protein output, probably by an action on the epithelium, whilst vagal stimulation and capsaicin stimulate submucosal glands. This method could be used to determine the factors which alter the rate of movement of plasma proteins into the airway lumen and the secretion of submucosal glands in vivo. PMID- 1446141 TI - Relationship of airway responsiveness to agents causing bronchoconstriction and cough in sensitized guinea-pigs. AB - The relationship between airway responsiveness to bronchoconstrictor- and cough inducing stimuli has been examined in Ascaris suum-sensitized conscious guinea pigs. Guinea-pigs were sensitized to Ascaris suum [4000 PNU and 100 mg Al(OH)3 i.p. on days 1 and 7] and then challenged with aerosolized antigen on days 21, 28 and 35. At day 35, antigen-exposure produced an early bronchoconstrictor response (EBR) and in about 50% of the animals also a late bronchoconstrictor response (LBR) commencing 4-8 h later. The bronchial responsiveness to inhaled histamine was increased in sensitized guinea-pigs and increased further 20-24 h after acute antigen challenge. Guinea-pigs developing only EBR were equally sensitive to histamine as those having both EBR and LBR. In contrast, the cough and reflex bronchoconstriction produced by inhaled citric acid (0.40 M, acting on capsaicin sensitive sensory neurons) and cigarette smoke (3 min exposure; exciting both capsaicin-sensitive neurons and rapidly adapting stretch receptors) were not altered by sensitization. Furthermore, acute antigen challenge did not alter the effect of citric acid as measured 24 h later. The antigen-induced airway hyperresponsiveness to histamine was not accompanied by an altered sensitivity of airway sensory nerves mediating cough (and reflex bronchoconstriction), demonstrating that bronchial- (airway obstruction) and sensory- (cough) hyperresponsiveness involve separate and independent mechanisms. PMID- 1446142 TI - The effect of GR32191 (a thromboxane receptor antagonist) on airway responsiveness in asthma. AB - Airway responsiveness to methacholine was measured in nine subjects (22-53 years, seven male) with chronic stable asthma. All subjects were taking inhaled beclomethasone (less than 1000 micrograms daily). The mean baseline FEV1 was 2.841 (77% of predicted) and the geometric mean PD20FEV1 was 31 micrograms. After a run-in period, the subjects were randomly allocated to two treatment periods with the specific thromboxane receptor antagonist GR32191, 40 mg four times daily for 3 weeks, and identical placebo capsules. A double-blind, placebo-controlled, cross-over design was employed with 4 weeks between the two treatment periods. Treatment with GR32191 did not result in any significant improvement in mean FEV1 (2.941 after placebo and 2.861 after GR3219; F7.71 = 1.02, P greater than 0.1) or PD20FEV1 (24.3 micrograms after placebo and 38.5 micrograms after GR32191; F7.71 = 0.59, P greater than 0.1). We conclude that thromboxane is not important in the maintenance of airway hyperresponsiveness in chronic asthma and that thromboxane receptor antagonists are unlikely to provide effective treatment for this group of patients. PMID- 1446143 TI - Role of endothelin in pulmonary function. PMID- 1446144 TI - Government health strategy: adding years to life. PMID- 1446145 TI - The nature of professional child abuse. PMID- 1446146 TI - Capillary blood glucose monitoring. AB - The complications associated with inaccurate capillary blood glucose monitoring and poor control of diabetes are well known. This article explores the research identifying potential causes of inaccurate testing, examines ways of minimizing error and investigates quality control issues. PMID- 1446147 TI - Chronic fatigue syndrome: cause, controversy and care. AB - There is much controversy as to whether chronic fatigue syndrome is a physical or a psychological illness. This article reviews the literature, explains where nursing stands in the controversy and makes suggestions for nursing care. PMID- 1446148 TI - Models of psychiatric consultation liaison nursing. AB - Recent developments in healthcare legislation have caused nurses to examine new and innovative styles of practice. Psychiatric consultation liaison nursing promotes collaboration among healthcare practitioners, raises standards of patient care and strengthens rather than negates the traditional role of the mental health nurse. PMID- 1446149 TI - Effects of mentorship on learners. AB - This small study was carried out in a unit for the care of the elderly to which second-level student nurses are allocated. No mentorship scheme was in operation in this unit and therefore the nursing officer, ward sisters, staff nurses and the nurse teacher in charge of the small school decided to compare the benefits of mentorship with non-mentorship. PMID- 1446150 TI - The Roper nursing model as an educational and research tool. AB - Models are thought to be of value as guides to professional practice; however, nursing models are often criticized. This article examines the concept of a model as a 'tool' and describes how the Roper model was used in a research project and proved to be both flexible and educationally sound as a teaching model. PMID- 1446151 TI - Nurses must learn to take risks. PMID- 1446152 TI - Passive euthanasia in palliative care. AB - Passive euthanasia is invariably practised in palliative care. This article aims to address the legal, moral and ethical implications of not hydrating dying patients and presents the results of a questionnaire assessing doctors' attitudes. PMID- 1446153 TI - Career development in intensive care: 1. AB - Nursing is becoming more specialized and leaner in terms of structure and therefore competition for positions is increasing. It is essential for nurses who are considering a career in intensive care to commence the planning process as early as possible. In this, the first of two articles, intensive care nursing and the career opportunities available will be examined. PMID- 1446154 TI - Patient satisfaction as a measure of quality in the care of the elderly. AB - This article examines the relevance of obtaining patients' views in the measurement of quality in nursing care. The literature on the selection of instruments that measure quality in the care of older people is reviewed. PMID- 1446155 TI - Casual dismissal of quality of life studies. PMID- 1446156 TI - Defining poverty. PMID- 1446157 TI - Effects of dipentylnitrosamine (DPNA) on the respiratory tract of rats. AB - Wistar rats (40 males and 40 females), treated over a period of 25 weeks with subcutaneous injections of dipentylnitrosamine (DPNA) at doses of 0, 62.5, 125 and 250 mg/kg body weight showed dose-dependent, sex-related, proliferative and metaplastic alterations in the upper and lower respiratory tract within one year. The biologic behavior of the induced lung tumors is very similar to that of human lung adenocarcinomas. PMID- 1446158 TI - Differentiation of Clara cell (distal type) antigen in human fetal bronchial epithelial cell line (HFBE). AB - A human fetal bronchial cell line (HFBE) grew in an undifferentiated pattern under conventional culture conditions. Despite a somewhat fibroblastic shape, however, they still maintained an immuno-reactivity to cytokeratin, carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). When grown on a collagen gel in a growth hormone-supplemented medium, their spindle shape became more conspicuous. With the additional supplement of 6 micrograms/ml vitamin A, most of the cells underwent differentiation by producing many bright inclusion bodies which proved to be strongly positive to periodic acid Schiff (PAS) and barely positive to alcian-blue (AB) staining. Electron microscopy revealed well-developed rough endoplasmic reticulum (rER), enlarged Golgi apparatus and many highly electron-dense secretory granules resembling those of Clara cells. Biochemical analysis demonstrated that HFBE cells cultured on collagen gel with vitamin A secreted products containing glycoconjugates of two different molecular weights. The higher molecular weight-product was identified as hyaluronic acid and the lower molecular weight-product as a mixture of neutral glycoproteins containing mainly N-linked glycoproteins whose glycans were of a complex type. While the secretion of hyaluronic acid was inhibited by vitamin A in a dose-dependent manner, that of the neutral glycoproteins was most enhanced by vitamin A in the range from the physiological concentration of 600 ng/ml to 6 micrograms/ml. A monoclonal antibody (SEC-41) generated against the secretory products with the lower molecular weight detected a glycoprotein of approximately 52 kd in the spent culture medium of differentiated HFBE cells. This antibody also reacted with the intra-cytoplasmic secretory granules in these cells. When tested on freeze-sectioned lung tissue, immunohistochemical reactivity of SEC-41 antibody was confined to Clara cells, some type II pneumocytes in the adult lung and respiratory epithelial cells of the fetal lung tissue. Moreover, this antibody could detect the secretory glycoproteins in the broncho-alveolar lavages (BAL) of two human cases. This paper has clearly demonstrated that cells derived from human fetal bronchial epithelium can be cultivated in an undifferentiated precursor state and under appropriate culture conditions they can be stimulated to undergo differentiation into a Clara cell type. PMID- 1446159 TI - Immunohistochemical expression of monoclonal antibodies (epi-1 and myo-1) derived from human breast cancer against rat mammary tumors. AB - Immunohistochemical expression of monoclonal antibodies epi-1 and myo-1 derived from human breast cancer cell line (HBC-4W) was examined for DMBA-induced rat mammary tumors. Antibody epi-1 reacted with luminal epithelial cells while antibody myo-1 reacted with myoepithelial cells of the mammary glands in rats, respectively. The reactions with both antibodies were markedly visible, in particular, in the normal mammary gland, tumor-like lesions and benign epithelial mammary tumors in rats, which showed clear two-cell-type structures. Among malignant mammary tumors, adenocarcinoma was strongly positive with antibodies epi-1 and myo-1. However, squamous cell carcinoma and adenoacanthoma mainly reacted with antibody epi-1. On the other hand, the intercellular matrices of pleomorphic cell sarcoma and stromal areas of the normal mammary gland or epithelial tumors were positive with antibody myo-1. PMID- 1446160 TI - The rat esophagus: ultrastructure and radiological aspects of tissue response after 1320 nm Nd:YAG laser irradiation. AB - Morphological tissue response towards laser treatment was investigated in the esophagi of adult Wistar rats by light- and transmission electron microscopy. The specimens were fixed by perfusion immediately, 2 days and 14 days after laser treatment in order to assess different stages of the healing process. The epithelium of the lasercentre was completely destroyed in the immediate group. The connective tissue showed damaged cells, fused collagenous fibres and occluded blood vessels. Smooth muscle cells presented a vacuolated sarcoplasm and pycnotic nuclei. The cross striation of skeletal muscle cells had disappeared and their nuclei were karyolytic. In a distance of 4 mm from the lasercentre all wall tissues had an almost normal appearance. After 2 days the morphological feature of the lasercentre was the same as in the immediate group. In a distance of 2 mm some layers of flat and intact epithelial cells were observed below the necrotic epithelium. The adjacent connective tissue was infiltrated by inflammatory cells. After 14 days the formation of granulation tissue had caused an occlusion of the lumen in the lasercentre. In a distance of 2 mm the lumen was patent and the wall tissues had been partly restored. As the rat esophagus serves as a model for esophagotracheal fistulae in newborn children we assume the 1320 nm Nd:YAG laser to be a possible application in occlusion of these fistulae. PMID- 1446161 TI - Electron microscopic and 31-P NMR studies of ischemic injured rat livers during preservation and reflow. AB - Ischemic injury induced during preservation and reperfusion contributes to post operative failure in liver transplantation. Hepatic injury and recovery from preservation was studied in an isolated rat liver model reperfused with oxygenated erythrocytes. In order to correlate morphological and functional findings, 31-P nuclear magnetic resonance spectroscopy and electron microscopy were used to investigate metabolic and ultrastructural changes during 6 hours of reperfusion. Following cold preservation, EM's showed a primary sinusoidal cell injury, whereas the hepatocytes were well maintained. During reperfusion, hepatocytes displayed further damage. The simultaneous presence of vacuolarly degenerated mitochondria and mitochondria of increased activity was noted. 31-P NMP spectra demonstrated initially a partial ATP-recovery. The maximum level of 60% of the control ATP-value could not be further increased. EM and 31-P NMR indicate that the progressive injury to the liver is due to microcirculatory malfunction induced by an endothelial cell damage, followed by injured hepatocytes themselves, and the consequent intracellular energy crisis that is produced. PMID- 1446162 TI - Hepatotoxicity of heated and oxygenated corn oil. AB - The present study was undertaken in rats to examine the hepatotoxicity of ingested heated and oxygenated corn oil. Activities of serum glutamic pyruvic transaminase markedly increased in the rats given heated and oxygenated corn oil for two weeks as compared with that of the control group. In the rats given heated and oxygenated corn oil, small fat droplets were found in the liver cells, but liver cell necrosis was not seen. Ultrastructurally, there was no conspicuous change in the liver cells, except for depletion of glycogen and dilatation of cisternae of rough and smooth surfaced endoplasmic reticulum. These experimental data show that ingestion of heated and oxygenated corn oil induces hepatic injury, and that the development of hepatic injury may relate to liver cell membrane damage due to active oxygen radicals contained in heated and oxygenated corn oil. PMID- 1446163 TI - Fluorenone and 2-benzoylfluorenone: different short-term effects on drug metabolizing liver enzymes and on cell proliferation. PMID- 1446164 TI - Endogenous and exogenous factors modifying the activity of human liver cytochrome P-450 enzymes. AB - Cytochrome P-450 dependent monooxygenases play a dual role for xenobiotic metabolism. On one hand they initiate the primary rate limiting step for the elimination of a bulk of drugs and organic chemicals. On the other hand they catalyze the formation of toxic metabolites from chemical carcinogens and many other toxic chemicals. Numerous studies have shown that their activity in animals is subject to the influence of various modifying factors, such as strain, species, sex, age, diurnal rhythm and the effect of enzyme inducers. Less is known about the influence of these factors on human cytochrome P-450 enzymes. Here we report the results of an extended study on human liver cytochrome P-450 performed with liver biopsies of 178 individuals taken for diagnostic purposes. The enzymatic activity was determined by the aldrin epoxidase assay indicating a variety of enzymes inducible by phenobarbital and by glucocorticoid and androgenic hormones. The frequency histogram of individual aldrin epoxidase activities showed a unimodal distribution and a variation factor of 100 between maximal and minimal activity. Individuals with severe liver diseases, such as cirrhosis and fatty liver, exhibited a 50% loss of enzyme activity. Age and sex did not significantly influence the enzyme activity. No significant correlation was observable between the rate of aldrin epoxidation and debrisoquine 4 hydroxylation, a prototype of a genetically controlled cytochrome P-450 reaction. We assume that the broad interindividual variation of epoxidase activities is more likely due to the influence of exogenous and endogenous inducers rather than to a genetic polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446165 TI - Glutathione homeostasis and turnover in the totally hepatectomized rat: evidence for a high glutathione export capacity of extrahepatic tissues. AB - Glutathione (GSH) homeostasis and turnover were investigated in totally hepatectomized (HX) rats. A technique is described to remove the liver totally, with preservation of the hepatic portal and vena caval vasculature. Euglycemia could be maintained with hourly infusions of 50 mg 100 g-1 b.m. of glucose after bolus i.v. injection of glucose at the same dose. The efficiency of the animal model was demonstrated by examination of paraclinical blood parameters: progressive increases in total plasma bilirubin and alkaline phosphatase activity were noted after HX; the other parameters tested were predominantly in the normal range during the observation period of 6 hours. Histological examination revealed an acute but reversible impairment of intestine and kidneys. These results indicate that the surgical procedure and postoperative care were able to secure sufficient physiological conditions for the experiments over a longer period. 3 to 6 hours after HX we observed a decreased but stable plasma GSH level in anhepatic rats (about 50% of the control value). The GSH levels of brain and kidney were not changed. With increasing time period after HX the heart and lung GSH levels were depressed. A small depression of muscle GSH concentration was observed 4 and 6 hours after HX. A progressive increase in the concentration of oxidized glutathione was seen in brain and kidney. Our observations could be indicative for a high GSH export capacity of extrahepatic tissues contributing about 50% of the total GSH influx into circulation. Probably, the skeletal musculature is an important GSH origin for plasma. PMID- 1446166 TI - Placental morphology and concentrations of glutathione (GSH and GSSG) and lipid peroxides (LPO) in two models of disturbed pregnancy of Uje:WIST rats. AB - Treatment of pregnant rats with heat-denaturated bacterial material (endotoxin model) or exposure to chronic restraint of prenatally lithium-treated pregnant dams (stress-model) were used as two models of disturbed pregnancy, both causing decreased fetal body mass. The quotient of fetal/placental mass was lowered in the endotoxin-group only. Placental mass and protein content were not changed significantly in both experimental groups, although a tendency to smaller placentae was noticed in the stress-group. Placental histology of the stress group did not differ from untreated controls. In the endotoxin-group an altered structure of the placental barrier was observed. Small decreases of GSH and GSSG in the endotoxin-group and of GSSG in the stress-group without significant changes of the GSH/GSSG relationship were measured in homogenates of the placental labyrinth. Moderate enhancement of LPO concentration occurred in the endotoxin-group and more distinctly in two litters of the stress-group, the latter being connected with high GSSG concentrations and low fetal/placental mass quotients. PMID- 1446167 TI - Proliferative glomerulonephritis in mice induced by sea snake (Aipysurus laevis) venom. AB - Aipysurus laevis venom has been shown to have a direct nephrotoxic effect in mice. A single subcutaneous injection (0.075 mg/kg body wt.) of the whole venom caused acute renal tubular degeneration and proliferative glomerulonephritis. The tubular changes appeared within 1 hour and remained for at least 14 days. Mesangial proliferative glomerulonephritis developed within 3-10 days, and is characterised by mild mesangial proliferation, mesangial and glomerular basement membrane deposits. This is followed by a partial resolution and subsequent mesangial sclerosis. The exact pathogenesis of venom-induced glomerulonephritis is not clear although it may have an immunological basis similar to that seen in human poststreptococcal glomerulonephritis. It was not possible to clarify the nature of the deposits by conventional immunohistochemical stains. PMID- 1446168 TI - Epidermis-specific gene expression in Pachyphytum. AB - Transcripts of exclusively epidermis-specific expression were obtained by differential screening of a cDNA library prepared from isolated epidermis tissue of a succulent plant, Pachyphytum. Six transcripts were selected and characterized by RNA gel blot hybridization. Five cDNAs represented abundant mRNAs found exclusively in the epidermis. In situ hybridizations with three of these transcripts further substantiated their epidermal location. While two transcripts were present in all cells of the epidermis, one transcript was enriched in subsidiary cells of the stomatal complexes. All of the transcripts were highly expressed in the protoderm of the shoot apical meristem. DNA sequence determination indicated that the mRNAs identified represent novel sequences, encoding yet unknown plant functions. These transcripts, their control elements, and their encoded functions should help to advance our understanding of epidermal cell determination and differentiation. PMID- 1446169 TI - Rhizobium meliloti elicits transient expression of the early nodulin gene ENOD12 in the differentiating root epidermis of transgenic alfalfa. AB - To study the molecular responses of the host legume during early stages of the symbiotic interaction with Rhizobium, we have cloned and characterized the infection-related early nodulin gene MtENOD12 from Medicago truncatula. In situ hybridization experiments have shown that, within the indeterminate Medicago nodule, transcription of the MtENOD12 gene begins in cell layers of meristematic origin that lie ahead of the infection zone, suggesting that these cells are undergoing preparation for bacterial infection. Histochemical analysis of transgenic alfalfa plants that express an MtENOD12 promoter-beta-glucuronidase gene fusion has confirmed this result and further revealed that MtENOD12 gene transcription occurs as early as 3 to 6 hr following inoculation with R. meliloti in a zone of differentiating root epidermal cells which lies close to the growing root tip. It is likely that this transient, nodulation (nod) gene-dependent activation of the ENOD12 gene also corresponds to the preparation of the plant for bacterial infection. We anticipate that this extremely precocious response to Rhizobium will provide a valuable molecular marker for studying early signal exchange between the two symbiotic organisms. PMID- 1446170 TI - A maize protein associated with the G-box binding complex has homology to brain regulatory proteins. AB - The G-box element is a moderately conserved component of the promoter of many inducible genes, including the alcohol dehydrogenase genes of Arabidopsis and maize. We used monoclonal antibodies generated against partially purified G-box binding factor (GBF) activity to characterize maize proteins that are part of the DNA binding complex. Antibodies interacted with partially purified maize GBF complexes to produce a slower migrating complex in the gel retardation assay. Immunoprecipitation experiments suggested that the protein recognized by the antibody is not a DNA binding protein in and of itself, but rather is associated with the DNA binding complex. These monoclonal antibodies were used to isolate cDNA clones encoding a protein that we have designated GF14. Maize GF14 contains a region resembling a leucine zipper and acidic carboxy and amino termini, of which the latter can form an amphipathic alpha-helix similar to known transcriptional activators such as VP16 and GAL4. Protein gel blot analysis of cell culture extract showed that a single, major protein of approximately 30 kD is recognized by anti-GF14; the protein is also present predominantly in the kernel and root. The deduced amino acid sequence of maize GF14 is more than 80% identical to Arabidopsis GF14 and Oenothera PHP-O, and is more than 60% identical to a class of mammalian brain proteins described as both protein kinase C inhibitors and activators of tyrosine and tryptophan hydroxylases. GF14 is found in a variety of monocotyledons and dicotyledons, gymnosperms, and yeast. This suggests a deep evolutionary conservation of a potential regulatory protein associated with a core sequence found in the promoter region of many genes. PMID- 1446172 TI - Transactivation of geminivirus AR1 and BR1 gene expression by the viral AL2 gene product occurs at the level of transcription. AB - Tomato golden mosaic virus is a bipartite geminivirus whose genome is divided between two circular DNA molecules. DNA A encodes functions necessary for viral DNA replication and encapsidation, whereas DNA B provides functions needed for movement in the host. Previous studies have shown that the viral AL2 gene product transactivates expression of the coat protein gene (AR1). We have investigated the role of the AL2 protein in the regulation of B component gene expression and examined the transcriptional and post-transcriptional components of this regulation. We found that AL2 protein is required for efficient expression of both the AR1 and BR1 genes, but not the BL1 gene. A comparison of steady state transcript levels and transcript levels determined by nuclear run-on analysis showed that activation of AR1 and BR1 gene expression by the AL2 protein occurs primarily at the level of transcription. These results provide an explanation for the lack of infectivity demonstrated by AL2 mutants, and suggest that the AL2 protein interacts with the cellular transcription machinery to activate the expression of rightward viral genes. PMID- 1446171 TI - TGA1 and G-box binding factors: two distinct classes of Arabidopsis leucine zipper proteins compete for the G-box-like element TGACGTGG. AB - Regulatory elements containing the sequence ACGT are found in several plant promoters and are recognized by various basic/leucine zipper (bZIP) proteins. The Arabidopsis G-box binding factor 1 (GBF1), initially identified by its ability to bind to the palindromic G-box (CCACGTGG), also interacts with the TGACGT motif if this hexamer sequence is followed by either the dinucleotide GG--as found in the Hex motif of the wheat histone 3 promoter--or GT. Here we describe the isolation of an Arabidopsis bZIP protein, denoted TGA1, that also recognizes ACGT containing sequences. However, TGA1 differs from members of the GBF family in the spectrum of base pair permutations flanking the ACGT sequence that are required for DNA binding. TGA1 primarily requires a TGACG motif and preferentially binds to those pentamers that are followed by a T residue. We show that although both TGA1 and GBF1 bind to the Hex motif (TGACGTGG), this binding can be distinguished on the basis of their specific DNA-protein contacts. Furthermore, TGA1 also differs from members of the GBF family in that it apparently does not form heterodimers with any member of this family. PMID- 1446173 TI - [Staphylococcus aureus nosocomial infections in an intensive care milieu (1985 1989) in Tunis]. AB - 221 strains of Staphylococcus aureus oxacillin resistant (MetiR) caused nosocomial infections were isolated from 1985 to 1989 in a medical intensive care unit. The survey of susceptibility to antibiotics was established according to the computerized data of disk susceptibility test. The resistance phenotypes to beta-lactams, aminoglycosides and macrolides were established for epidemiological study. S. aureus infections were mainly bacteraemia (31%) and peritonitis (12%). These isolates were resistant to oxacillin with a high level (mean MIC 386 micrograms/ml). Their resistance phenotypes were MLSBc (constitutive resistance to macrolides, lincosamine and streptogramines B) in 53% and S + KGT (resistance to streptomycin, kanamycin, gentamicin and tobramycin) in 61%. All the isolates were susceptible to pristinamycin and vancomycin (MIC 0.1 and 2 micrograms/ml). These phenotypes related to the spread of multiply drug resistant strains were responsible of nosocomial outbreaks. Strains with the same pattern of resistance were isolated among the medical staff and in the environment. Infection control measures allowed to stop these outbreaks. PMID- 1446174 TI - [The reappearance of chancroid in Algeria]. AB - After 35 observations of the chancroid observed in the department of dermato venereology of the University Hospital of Tlemcen (West Algeria) from August 1988 to December 1991, we are led to analyze the flare of this sexual transmitted disease. The principal affected subjects are single male no older than 30 years, having had sexual intercourse with prostitutes (30/35). Less than 10 days (19/29) after the sexual contacts, the ulcer appears, and most often unique (25/35), mildly painful, accompanied frequently by adenopathies (31/35). The contamination took place mainly in Bel Abbes--city located at 90 km from Tlemcen--(12 cases), in Tlemcen (4 cases) and Morocco (5 cases). The treatment based on sulfonamides, erythromycin and tetracycline or doxycycline, has been constantly efficient. No concomitant HIV infection has been revealed. The chancroid is the first STD observed in our department in 1991, and also, the first cause for genital ulcer. PMID- 1446175 TI - [Drug sensitivity study of Plasmodium falciparum in the city of Yaounde (Cameroon)]. AB - In July 1990, the in vitro chemosensitivity of 22 isolates of Plasmodium falciparum was assessed by an isotopic semi-microtest in Yaounde, Cameroon. Out of them, 54.5% were resistant to chloroquine, 28.6% to amodiaquine, 4.8% to quinine and 4.5% had a decrease of sensitivity to mefloquine. A strong positive correlation between the IC50 of the antimalarial drugs compared by pairs was detected. PMID- 1446176 TI - [Falciparum malaria in French residents in Yaounde]. AB - In South Cameroon, malaria is a disquieting problem. It represented 2.6% of consultants and concerned each year 10% among French residents. We have included 310 cases of Falciparum malaria between January 1, 1990 and December 31, 1990. There were 207 adults and 103 children with a mean age of 26 years. The duration of the stay was over one year in 137 cases and lower than 1 year in 183 patients. The chemoprophylaxis was correct in 194 patients according to the dose and duration. Forty-nine patients followed a combination of chloroquine and proguanil. Malaria attack was observed in 272 patients. Among them, there were 95 children. A severe malaria occurred in 38 cases. Mean parasitemia was of 0.24% (range: 0.002-7.5%). Therapy regimen was quinine: 36 cases, halofantrine: 266 cases, amodiaquine: 7 cases and association MFP (Fansimef) in 12 patients. The study shows the importance of malaria in an endemic area among expatriates despite the observance of chemoprophylactics regimens including proguanil. PMID- 1446177 TI - [Specifics of the epidemiology of urinary schistosomiasis in Mauritius]. AB - Early observations on this disease were made in Mauritius by Chapotin (1812) before the discovery of Schistosoma haematobium. Bulinus cernicus, the snail intermediate host, one of the nine species within the B. forskali group, is restricted to the island and the disease is not occurring in the neighbouring islands of La Reunion and Rodrigues. Under laboratory conditions, the snail susceptibility to the Mauritian strain of S. haematobium has been demonstrated. But the infection rate of the snail remains very low and the transmission of the disease is sporadic except in three foci. Its occurrence is not linked with agriculture or irrigation but is closely related to other man/water contacts in the rivers. Without clinical significant signs, the disease, quite different of the historic description, is largely underestimate. The snail is well adapted to the climatic conditions on Mauritius with a remarkably resistance to long drought periods. In fact, distribution of snail and evolution of population size fluctuate dramatically. Canalization and drainage of rivers, streams and marches since the beginning of malaria outbreak, widespread use of pesticides during the antimalaria spraying campaigns, only overhead irrigation, permanent maintenance of the lined canal system, induced many ecological constraints to possible snail habitats. Without animal reservoir of infection, control of urinary schistosomiasis or even its eradication looks feasible through a large school case-finding eventually associated with mollusciciding activities in the main foci. PMID- 1446178 TI - [Autochthonous strongyloidiasis in the north of France]. AB - The authors discuss four cases of indigenous strongyloidiasis, which were detected in northern France during the past twenty years. In our hemisphere, the limits of this helminthiasis range between the 50th and the 53rd parallels of latitude. In two cases, indoor contamination must be suspected; in the third case, transmission has been facilitated by insalubrity and crowding; the fourth case was related to the activities of a dustman in camping sites. Nose bleedings were noticed in two cases and the haemorrhagic manifestations in strongyloidiasis are mentioned. PMID- 1446179 TI - [Visceral leishmaniasis in Algeria. Cases reported of visceral leishmaniasis (1985-1990)]. AB - Following their epidemiological studies of visceral leishmaniasis in Algeria, the authors report in this survey 1122 cases diagnosed in different hospitals of the country from 1985 to 1990. The authors mention that after a temporary decline observed during the last decade, they take part to a disquieting course of this disease. PMID- 1446180 TI - [Seroepidemiological study of visceral leishmaniasis in school children in the Iferouane oasis (Niger)]. PMID- 1446181 TI - [The Anopheles fauna and the transmission of human malaria in Kinshasa (Zaire)]. AB - A longitudinal epidemiological study of malaria and its vectors was conducted in Kinshasa. 264 night-bite collections on human bait (1,056 man nights) and 384 collections of the house-resting fauna were carried out from April 1989 to October 1990. The anophelian fauna was identified and inventoried, 7 Anopheles species were found: Anopheles gambiae, An. funestus, An. paludis, An. hancocki, An. counstani, An. brunnipes, and An. nili. A single species, An. gambiae s. l. is responsible for the transmission of malaria, it represents 93.27% of the anopheline fauna. The average number of anophele bites man day was 16.28 bites/man/night, it varied between 1 b/m/n in urban area to 26.05 b/m/n in semi rural area. The average of the sporozoite index for An. gambiae was 3.3%, but it varied from 0% in the urban area to 6.52% in the semi-rural area. The entomological inoculation rate (h) was 197 infective bites per year. This rate fluctuated from 1 infective bite each 128 nights in urban area to 1.7 infective night-bite in semi-rural area. Other epidemiological index were also determined: the level of daily survival rate (p = 8.75 days), the vectorial capacity of 17.97 and the Macdonald's stability 3.5 bites on man taken by a vector during its entire lifetime. PMID- 1446182 TI - [Study of phlebotomus sandflies in Syria]. AB - An entomological survey was carried out during 1986 in ten provinces of Syria representative of the main natural areas of this country. 932 sandflies were caught with aspirators in domestic resting sites. Captures are analysed for each species. PMID- 1446183 TI - [Survey of the infestation level of the Ixodes ricinus tick by Borrelia burgdorferi. Complimentary report]. AB - In a recent report, we gave results of a 4 year consecutively survey (1987 to 1990) of the level of Ixodes ricinus nymphs infested by Borrelia burgdorferi in two forests of the western part of France. This brought us to conclude that there was a relative stability for this level in course of time. Results of this survey kept on in 1991 oblige us to partly modify our conclusion, on account of an important dropping of the tick infection frequency in one of the two forests, this perhaps in connection with a large observed decreasing of the micromammals populations (but not of ticks ones) due probably to an exceptional drought during all the 1990 year. PMID- 1446184 TI - Screening children's hearing. PMID- 1446185 TI - ABR screening for acoustic neuromata: the role of rate-induced latency shift measurements. AB - The audiological assessment of patients considered 'at risk' for an acoustic neuroma is problematic when the patient has a severe hearing loss. The utility of ABR rate-induced latency shift (RLS) measurements was investigated in 189 patients who had passed a conventional assessment and 31 patients with an acoustic neuroma. A test based on the RLS of wave V using rates of 11.1 s-1 and 88.8 s-1 had a sensitivity of 89.5% and a specificity of 90.8% when applied with a dual interpretive criterion which included the loss of wave V at the higher rate. This test was included in an ABR screening protocol which had a sensitivity of 100% and a specificity of 97.9%. The RLS test requires no correction for age, sex, hearing loss or stimulus intensity and may be used in patients with severe hearing loss for whom other ABR tests are inappropriate. PMID- 1446186 TI - Temporal modulation transfer functions for band-limited noise in subjects with cochlear hearing loss. AB - The modulation depth required for the detection of sinusoidal amplitude modulation was measured as a function of modulation rate, giving temporal modulation transfer functions (TMTFs). The carrier was a one-octave wide noise centred at 2 kHz, and it was presented in an unmodulated background noise lowpass filtered at 5 kHz. Three subjects with unilateral cochlear hearing loss were tested. For each subject, the normal ear was tested both at the same sound pressure level (SPL) and at the same sensation level (SL) as the impaired ear. The TMTFs were essentially the same for the normal and impaired ears, both at equal SPL and at equal SL. The better ears of three subjects with bilateral cochlear losses were also tested. Again, TMTFs were essentially the same as obtained for normal ears. These results suggest that temporal resolution is not necessarily adversely affected by cochlear hearing loss, at least as measured by this task. PMID- 1446187 TI - An audit of hearing aid quality in Denmark. AB - This investigation was aimed towards an evaluation of the quality of hearing aids, dispensed from a National Hearing Health Service. During a twelve month period all subjects attending the hearing aid servicing section were recorded, and the reason for the visit noted. A total of 4450 people attended (45% males, 55% females) with a median age of 71 years, range 8-99 years. Among these 60.4% of attendances could be ascribed to defective hearing aids. Among the defective hearing aids 20.6% had been used less than one year and 91.4% of the defective aids had been used less than four years, that is within the guarantee period. The recording demonstrated that specific series of aids have a defect rate of 6.6 70.9% within the first year of use. A comparison between the frequency of defects in different types of hearing aids (BTE, ITE, ITC and other hearing aids) was performed indicating that there is a risk of 8.6% that BTE will be defective within one year of provision. As 20.6% of the applicants' defective hearing aids had been used less than one year, it is concluded that the quality of hearing aids should be improved; the hearing aid manufacturers' main categories for fault finding can be used in the audiological departments within the National Hearing Health Service; the recording offers valuable data on the quality of hearing aids, and specifically poor series can be revealed within a limited period. PMID- 1446188 TI - Latency stability of auditory brainstem responses in children aged 10-12 years compared with younger children and adults. AB - Previous articles have reported the results of using standard clinical procedures in our laboratory for testing auditory brainstem responses (ABR) in a repeated measures design, in order to quantify ABR latency and amplitude stability in normal young adults. In a subsequent paper, these findings were extended to include the results of similar procedures in a group of seven children ranging in age from 5 to 7 years. The current experiment involves repeated-measures ABRs in a group of nine children ranging in age from 10 to 12 years. Results indicate that while these older children show the expected similarities with adults in terms of ABR peak latencies, their latency stability values are in some cases significantly lower than adults. At the same time, ABR stabilities measured in the older children show some differences compared to data from the younger children studied previously. For all groups, the same types of patterns are observed: (1) significant differences contrasting the degree of between-subject v. within-subject latency stability; (2) clear individual differences characterizing subjects; (3) within-subject distinctions according to ear of stimulation; and (4) instances of good replicability of the 'latency-stability profiles' calculated for one set of repeated waveforms v. a second set collected later in testing. PMID- 1446189 TI - Recommended procedure for tympanometry. British Society of Audiology. PMID- 1446190 TI - Comparison of different methods of repair of long peripheral nerve defects: an experimental study. AB - In order to compare the performance of free nerve grafts, vascularised nerve grafts, and freeze-thawed muscle autografts for the repair of long nerve defects an experimental study was undertaken in the rabbit peroneal nerve. 5 cm defects were repaired using each method. Recovery of function was assessed after 250 days using sensory and motor physiology, and histological examination of the nerve. Reliable recovery occurred with both types of nerve graft but not with muscle grafts. Vascularised nerve grafts performed better than free nerve grafts on all parameters measured but this only reached statistical significance for sensory receptive areas and myelinated fibre diameters distal to the grafts. The role of each method of repair in peripheral nerve surgery is reviewed. PMID- 1446191 TI - Histomorphological observations on dermal repair in expanded rabbit skin: a preliminary report. AB - In 11 New Zealand rabbits, small tissue expanders were placed in a pocket between the dermis and the panniculus carnosus and inflated during a period of 10 days. Animals were killed immediately after the inflation procedure (Group I, N = 4), 25 days thereafter (Group II, N = 5), and 35 and 55 days thereafter (Group III, N = 2). Dermal connective tissue architecture was studied by routine light microscopy. Specimens in group I showed a striking disturbance in polarity of the dermal collagen bundles. These changes were accompanied by a clear increase of cellular infiltration. In groups II and III, the collagen polarity showed a tendency to recover to normal, while cellular infiltration was decreased. The current findings indicate that there is a spontaneous repair of the damaged dermal collagen in expanded skin with time. PMID- 1446192 TI - The effects of ultraviolet irradiation on wound contraction in the hairless guinea pig. AB - Ultraviolet radiation has been shown to alter wound tensile strength and evoke a number of intracellular changes in fibroblasts. We examined the effects of relatively high doses of ultraviolet radiation on subsequent wound contraction of circular wounds in the hairless guinea pig model. Female hairless guinea pigs were divided into two experimental groups receiving 80 J/cm2 or 480 J/cm2 every other day for 16 weeks. Age-matched unirradiated animals were used as controls. After exposure, all animals had either a 4 mm punch biopsy (80 J/cm2) or a 2.4 cm diameter ((480 J/cm2) Groups 3 and 4) circular area excised from the dorsum. The extent of wound enlargement immediately following wounding of the irradiated animals was decreased as compared to the controls. The rate of wound contraction was significantly lower during early stages of wound contraction in each group of irradiated animals, and wound contraction was significantly slower overall in both groups of irradiated animals compared to controls. PMID- 1446193 TI - The beneficial effect of cyclosporin-A on the no-reflow phenomenon in rat skin island flaps. AB - The no-reflow phenomenon is one of the factors that increase morbidity in flap and replantation surgery. Prevention and treatment of the phenomenon is an area of intense current research. This study investigated the possible effect of cyclosporin administered systemically on survival of skin flaps subjected to ischaemia-reperfusion injury. Cyclosporin treated flaps showed a statistically significant increase in survival areas regardless of the time of infusion (p < 0.01). These findings suggest that cyclosporin could be valuable in preventing or treating no-reflow in critical flaps. Possible mechanisms of action are discussed. PMID- 1446194 TI - The effect of continuous topical application of heparin on flap survival. AB - To evaluate the beneficial effects of heparin on flap survival area, an experimental study was carried out on dorsal flaps in rats. Topical applications of heparin, released from a silicone gel sheet onto the critical area (which generally necrosed without treatment), resulted in an increase in the flap survival area and rate as compared to controls (p < 0.01). When heparin was applied topically but solely to an area proximal to the critical area however, no increase in the survival area resulted. PMID- 1446195 TI - Mid-facial sensation following craniofacial surgery. AB - During mid-face advancement and correction of orbital dystopia, the infraorbital nerves are always stretched and displaced by the orbital floor osteotomies and bone displacement, and are at risk of damage. We have found no published work that has investigated the function of the infraorbital nerves following elective craniofacial procedures. In this study the cheek sensation and tooth sensibility in 20 patients who have had either mid-face advancement or correction of orbital dystopia was assessed. The function of the infraorbital nerve is largely undisturbed by the osteotomies and bone displacement performed during these procedures. A small proportion of patients could not feel cold in their anterior maxillary teeth, suggesting that there is damage to the anterior superior alveolar nerve branch of the infraorbital nerve. PMID- 1446196 TI - Critical analysis of methods of reconstruction of exenterated orbits. AB - Reconstructive procedures were used on 14 patients who had undergone orbital exenteration and radiotherapy for malignant tumours. All patients were tumour free after a follow-up of between 5 and 18 years. Reconstruction was carried out in 3 stages. In the first operation the orbit was filled, in the second the orbital rims and eyelids were shaped, and in the third a cavity for a static eye prosthesis was created. Critical assessment of results showed that the first stage alone produced a marked improvement in appearance and occluded existing fistulae. The subsequent procedures improved aesthetic results further. Difficulties were encountered from retraction of the tissues and insufficient tissue mobility. PMID- 1446197 TI - Tissue expansion in the treatment of tubular breast deformity. AB - Four cases of tubular breast deformity were treated using tissue expansion. The expanders were inserted through either an axillary or an infra-mammary approach in as low a position as possible. The expanders were then over-inflated and allowed to settle for a period of time before removal and insertion of a permanent implant. We present our experience using this technique and the complications and problems we had to deal with. PMID- 1446198 TI - Lignocaine vs bupivacaine in prominent ear correction: a controlled trial. AB - Thirty patients were assigned to two equal groups to compare the effects of ear infiltration with bupivacaine versus lignocaine prior to correction of prominent ears. There was a statistically significant decrease in narcotic requirement in the first 4 h postoperatively in the bupivacaine group, associated with a decrease in the antiemetic requirement. The choice of local anaesthetic did not significantly affect the incidence of vomiting. PMID- 1446199 TI - Wound sterilisation: cautery vs CO2 laser. AB - Al-Qattan et al. (1989) demonstrated that for difficult infected surgical wounds the CO2 laser was a much more effective sterilising agent than a standard surgical scrub (P < 0.005). This study compares the effectiveness of a standard electrocautery unit against that of the CO2 laser for wound sterilisation. Cautery sterilisation of infected wounds was found to be significantly superior to that of the CO2 laser (P < 0.05). Infection was noted in 4% of the cautery sterilised wounds and 12% of the wounds treated with CO2 laser. Case reports are also presented to demonstrate the clinical applications and effectiveness of this technique. PMID- 1446200 TI - One-stage repair of multiple bed sores. AB - Management of multiple bed sores which are deep and of large area presents a special challenge to the surgeon, especially when all the sores are within the same anatomical region. We are presenting our experience of one-stage repair of bed sores. Representative cases are discussed including a patient who needed four flaps to close the ulcers. There were no major complications in any of the patients. We advocate one-stage repair in selected patients. PMID- 1446201 TI - First dorsal metacarpal artery flap cover for extensive pulp defects in the normal length thumb. AB - Use of the first dorsal metacarpal artery flap to cover extensive pulp defects in the normal length thumb in five patients is described. The advantages of the procedure include provision of sensate cover of exposed distal phalanx to the tip of the thumb with minimal donor site morbidity. Its use, particularly in the older patient, with immediate postoperative mobilisation and the avoidance of nerve repair or more complicated microsurgical procedures, is discussed. PMID- 1446202 TI - Clinical characteristics of vascular leiomyoma of the upper extremity: report of 11 cases. AB - Clinical features of vascular leiomyoma of the upper extremity which have not been described or have been described incorrectly are documented with a report of 11 consecutive cases seen within the past 11 years. All patients were followed without recurrence or surgical morbidity. Vascular leiomyoma has been described as a painful nodule found more frequently on the extensor surfaces, but in our experience spontaneous or paroxysmal pain is exceptional and the tumour tends to be located on the volar surface when it is in the hand. In the digit, they tend to be found at the base away from the midline, and not seen distal to the DIP joint. PMID- 1446203 TI - The "lazy-V" de-epithelialised turn-over fasciocutaneous flap in the reconstruction of skin defects after tendo Achilles repair. AB - Few methods of closure of skin defects lying over the tendo Achilles have been described. The de-epithelialised turn-over flap is one of them but it cannot be used in the presence of a scar proximal to the defect. We describe a modification ("The Lazy-V") of the de-epithelialised turn-over flap which gives it a rotation arc, thus enhancing the versatility of the procedure. This modification is presented with an illustrative case report and a review of the literature. PMID- 1446204 TI - Supernumerary nostrils. AB - We encountered a rare case of four asymmetrical nostrils 10 years ago. The upper nostrils looked normal while the lower appeared as sinuses. The lower pair communicated with the nasal cavities but the upper pair was obliterated. There was a thick columella and an elongated continuous nasal septum separating the nasal cavities. The left nostril sill was thicker and situated higher than its counterpart. When the patient was 3 months old, the lower sinuses were trimmed and closed primarily, while the upper pair was perforated and kept patent with a silicone tube covered with a split thickness skin graft. Four years later, a revision was performed. Stages of operation were preferred as nasal growth was concerned. The result was satisfactory following 10 years of observation. PMID- 1446205 TI - Long term follow-up of a case of Kasabach-Merritt syndrome successfully treated with radiotherapy and corticosteroids. AB - Kasabach-Merritt syndrome is the association of thrombocytopenia, spontaneous bleeding, and enlargement of a haemangioma. It is caused by an intense, self perpetuating process of clot-formation and lysis within the abnormal vascular channels of the haemangioma, and results in consumption of platelets and clotting factors. Treatment involves ablation of the lesion with or without pharmacological manipulation of the coagulation and fibrinolytic systems. No single therapeutic modality is universally successful but a combination of radiotherapy and corticosteroids can result in a dramatic, immediate response with minimal long term complications. PMID- 1446206 TI - Flexor carpi radialis myocutaneous flap. PMID- 1446207 TI - Polyurethane foam covered prostheses. PMID- 1446208 TI - Interaction between verbal and gestural language in progressive aphasia: a longitudinal case study. AB - The objective of this longitudinal study is to investigate the on-line interaction between praxis and linguistic abilities in a progressive aphasia case. During 3 years of evolution, procedural discourse of a progressive aphasic patient was videotaped five times, allowing us to analyze the progression of both language and gestural production as well as the interaction between these two. We anticipated that, in the absence of apraxia, the patient would compensate for her speech deficit by producing progressively more and more meaningful gestures. Our compensatory hypothesis was confirmed but the compensation was not as efficient as one would expect given the absence of apraxia. With the progression of the speech deficit, the patient could not replace some verbs by pantomimes that were otherwise accompanying her discourse in the preceding testing sessions. We suggest that such a compensatory ability may constitute one important characteristic of the progressive aphasia syndrome. PMID- 1446209 TI - Impairment of temporal organization of speech in basal ganglia diseases. AB - Absolute and relative speech timing were examined in patients suffering from Parkinson's, Huntington's, and Wilson's disease. The task was to speak a standard sentence 10 times, first slowly, and then successively faster up to maximum rate. All patient groups had low maximal speech rates and showed decreased variability of speech rate. The duration of pauses between words was the same as in normals and the relative time structure of the test sentence was basically preserved. For comparison, two cases with nonfluent aphasia had even slower speech rates, large increases in pause duration, and major changes in relative speech timing. The results show the same type of alterations of the temporal organization of speech as those characteristic for rapid alternating limb movements in such patients. They support the view that the speech and skeletomotor systems share common neural control modes despite fundamental biomechanical differences. The common denominator between the speech and the skeletomotor disturbances in basal ganglia diseases may be the undamping and slowing of a fast central oscillator. PMID- 1446210 TI - Dissociation of mechanisms of reading in Alzheimer's disease. AB - The role of spelling-to-sound correspondence rules in oral word reading was investigated by asking patients with Alzheimer's Disease (AD) and normal controls to read aloud pronounceable letter strings that do not happen to be real words. These pseudowords were of two types: those that have orthographically similar "neighbors," and those that have no neighbors. The patients with AD were mildly impaired relative to the normal controls in reading pseudowords with neighbors, but were markedly impaired in reading pseudowords with no neighbors. The results are interpreted as favoring a model of reading in which words and pseudowords are normally read via the same lexical mechanism. An ancillary route involving the conscious application of spelling-to-sound rules is available only to cognitively intact readers. PMID- 1446211 TI - Dissociation between linguistic and nonlinguistic gestural systems: a case for compositionality. AB - This paper addresses the issue of the separability of disorders of sign language from disorders of gesture and pantomime. The study of a left-lesioned deaf signer presents one of the most striking examples to date of the cleavage between linguistic signs and manual pantomime. The left-hemisphere lesion produced a marked sign language aphasia disrupting both the production and the comprehension of sign language. However, in sharp contrast to the breakdown of sign language, the ability to communicate in nonlinguistic gesture was remarkably spared. This case has important implications for our understanding of the neural mediation of language and gesture. We argue that the differences observed in the fractionation of linguistic versus nonlinguistic gesture reflect differing degrees of compositionality of systems underlying language and gesture. The compositionality hypothesis receives support for the existence of phonemic paraphasias in sign language production, illustrating structural dissolution which is absent in the production of pantomimic gesture. Understanding the neural encoding of compositional motoric systems may lead to a principled anatomical account of the neural separability of language and gesture. This case provides a powerful indication of the left hemisphere's specialization for language-specific functions. PMID- 1446212 TI - Hemispheric dissociation in judging semantic relations: complementarity for close and distant associates. AB - In two lateralized tachistoscopic experiments, we presented (i) pairs of nouns with close or distant semantic associations or (ii) pairs of nouns which were randomly matched and later rated by the subjects as to their semantic distance. In both experiments, words presented to the right visual field were more frequently judged as semantically close in meaning than words presented to the left visual field (LVF), whereas words presented to the LVF were more frequently judged as semantically distant. The results are discussed in relation to hemispheric language functions and current models of cerebral laterality. PMID- 1446213 TI - Educational level and the word frequency effect: a lexical decision investigation. AB - It is known that speed and accuracy in recognizing words are constrained by the frequency of occurrence of these words ("frequency effect"). This study examines the relationship between educational level and the word frequency effect. We postulated that individual exposure to words that are rated lower in frequency tables should be greater among subjects with higher education and therefore hypothesized that the magnitude of the frequency effect should not be as marked within such a population as among subjects with a lesser educational level. A total of 40 neurologically healthy adults, half with an average of 18 years of formal education and the other half with an average of 11 years, participated in a lexical decision experiment. Results confirmed our hypothesis; that is, significant frequency effects on reaction times were obtained in both groups but this effect was of greater magnitude for the less educated as opposed to the more educated subgroup. The significance of this finding is discussed by reference to current models of word recognition. PMID- 1446214 TI - Phrenological studies of aphasia before Broca: Broca's aphasia or Gall's aphasia? AB - The history of aphasia is usually taken to begin with Broca's (1861a,b) discovery of the correlation of aphemia with damage to the posterior inferior portion of the frontal lobes and the subsequent relation to left hemisphere. That there were prior, even biblical, references to aphasia is not in dispute, nor that, according to Benton and Joynt (1960), almost all the clinical forms of aphasia had been described prior to 1800. The significance of Broca's case studies, therefore, lies in the association of motor aphasia with focal pathology in the frontal lobe. This paper examines the status of aphasia localization prior to Broca, and, specifically, the extent to which Broca's discovery may have been anticipated by the phrenologists. PMID- 1446215 TI - Self-repair in dialogues of schizophrenics: effects of hallucinations and negative symptoms. AB - This paper concerns the discourse features of verbal hallucinations and negative symptoms of schizophrenia. A total of 46 schizophrenics, varying in verbal hallucination and in negative symptoms status, and 22 controls were tested on the Reporter Test. The frequency with which they issued inadequate instructions, attempted to repair the inadequacies, and the success of repairs were compared. We observed that schizophrenics, on the whole, issued more wrong and incomplete instructions. This was in part related to their worse working memory, but it was not affected by verbal hallucinations or negative symptoms. We observed, further, that schizophrenics had no particular problems monitoring messages for inadequacies. We did find, however, that schizophrenics with verbal hallucinations had a specific problem with self-repairing wrong instructions. We interpret these results in the framework of Hoffman's (1986b) plan disruption based model of verbal hallucinations; the Frith (1987) and Frith and Done (1988) internal monitoring model of positive and negative symptoms; and finally Frith and Frith's (1990) model of negative and positive schizophrenia and we use the results to specify the models. PMID- 1446216 TI - Everything is the same: a note on Caramazza and Hillis (1989) "The disruption of sentence production: some dissociations". PMID- 1446217 TI - Not everything is the same: some things are worse than others. A response to Tesak. PMID- 1446218 TI - Language lateralization in bilinguals: more not less is needed: a reply to Paradis (1990). AB - Paradis (1990) took an extremely pessimistic view of research to date looking at the lateralization of cerebral function in bilingual subjects. We, however, argue that some of his conclusions are, in fact, incorrect, while others speak more to the youth of the field. The problems in the latter body of work are now acknowledged and are being overcome. That the shortcomings are recognized seems to be more a case for satisfaction than of despair. PMID- 1446219 TI - The Loch Ness Monster approach to bilingual language lateralization: a response to Berquier and Ashton. AB - To continue to search for a difference in language lateralization between bilinguals and unilinguals is at best a futile task in the face of all the clinical evidence to the contrary and inconsistent experimental findings. No amount of refining of dichotic, tachistoscopic, or concurrent task procedures, or statistical sophistication, is likely to tap the differential reliance on pragmatic cues that might very well exist in some nonbalanced bilinguals. PMID- 1446220 TI - Polyclonal antibody localizes glia maturation factor beta-like immunoreactivity in neurons and glia. AB - A rabbit polyclonal antibody (91-01) was raised against recombinant human glia maturation factor beta (r-hGMF-beta). The antibody did not cross-react with a number of other growth factors on ELISA test. When compared with the monoclonal antibody G2-09 previously obtained, 91-01 immunoblotted the same protein band in rat brain extract. However, unlike G2-09 which immunostained only astrocytes and Bergmann glia, 91-01 stained neurons as well. Many but not all neurons in the central and peripheral nervous system were positive for GMF-beta. The larger cell population stained by the polyclonal antibody was most likely due to its increased sensitivity, although other explanations are possible. The presence of GMF-beta-like immunoreactivity in both neurons and glia raises the possibility of a wider range of cell-cell interaction than was previously considered. PMID- 1446221 TI - Amygdala stimulation produces two types of hippocampal afterdischarges in the urethane-anesthetized rat. AB - How seizures spread during epileptiform events has been the subject of intensive investigation over the years. The present study explored the relationship between the amygdala and the hippocampus during afterdischarges. Stimulating electrodes were placed in the amygdala and CA3 regions on the left side in urethane anesthetized rats. Recording microelectrodes were placed in the dentate gyrus on the left and the CA1 cell layer on the right. Afterdischarges were elicited by stimulus trains between 10 and 50 Hz to the amygdala. Most of the afterdischarges consisted of broad positive potentials in dentate gyrus and no shift of the DC potential. When the stimulus trains were repeated, the afterdischarge evolved, first by spreading to the contralateral side and then by the appearance of maximal dentate activation. The onset of maximal dentate activation was indicated by the appearance of bursts of large amplitude population spikes and a negative shift of the DC potential. These data demonstrate that two types of afterdischarges can be produced in the hippocampus of the anesthetized rat after amygdala stimulation. The observations support the hypothesis that maximal dentate activation represents synchronized reverberatory activity throughout the hippocampal-parahippocampal circuit and indicate that amygdala stimulation can access this circuit in the anesthetized animal. PMID- 1446222 TI - Suppression of nociceptive responses in parafascicular neurons by stimulation of substantia nigra: an analysis of related inhibitory pathways. AB - A total of 166 neurons in parafascicular nucleus (PF) were studied, 85 from intact animals, 72 following dorsal spinal cord transection (D.Sp.C.X.), and 9 following complete transection of the spinal cord. Two patterns of nociceptive responses were identified following noxious stimulation and these responses were classified as 'nociceptive-on' and 'nociceptive-off' neurons, respectively. The effects of stimulating the substantia nigra (SNS) on the spontaneous and on the nociceptive evoked discharges were observed and compared in intact, D.Sp.C.X. and completely transected spinal cord rats. The results show that SNS significantly suppresses both the spontaneous and the nociceptive evoked discharges elicited by peroneal nerve stimulation. With an intact spinal cord, SNS suppressed both the spontaneous [-37 +/- 3.2% (P less than 0.05)] and the nociceptive evoked discharges [-52.8 +/- 2.8% (P less than 0.01)] of the 'nociceptive-on' cells respectively, while in the 'nociceptive-off' cells the same stimulation elicited an even more prominent suppression upon both discharges (-47.7 +/- 5.4%, P less than 0.01 and -64.9 +/- 5.0%, P less than 0.01), respectively. After D.Sp.C.X., the suppressive effects on the 'nociceptive-on' cells following SNS were diminished (-28.1 +/- 3.5% and -36.9 +/- 2.6%, respectively) but not abolished, while in the 'nociceptive-off' cells, the inhibitory effects on SNS were unchanged. In addition, the suppressive effects of SNS on the spontaneous activity of PF neurons in cases with completely cut spinal cords remains unchanged. These results suggest that SNS modulates the spontaneous and the noxious evoked responses of the PF neurons by way of supraspinal connections besides the previously described descending projecting pathways. PMID- 1446223 TI - Effects of atropine on hippocampal theta cells and complex-spike cells. AB - The medial septal nuclei are essential for the naturally occurring hippocampal theta rhythm. Evidence that the rhythmic activity of the septum is carried via cholinergic afferents to the hippocampus has been: (a) the existence of a cholinergic septo-hippocampal projection, and (b) the sensitivity of one type of theta rhythm to antimuscarinic agents or cholinergic depletion. The muscarinic action of acetylcholine on pyramidal cells, however, is too slow to carry even a 4 Hz signal. Recent in vitro studies have confirmed a fast excitatory response by some hippocampal interneurons to muscarinic agonists. In urethane anesthetized rats, iontophoretic application of atropine to 17 hippocampal theta cells (presumed interneurons) during the theta rhythm, reduced their firing rates to an average of 24% of control rates. The effect of iontophoretic atropine application to 4 CA1 complex-spike cells (presumed pyramidal cells) was a selective elimination of their bursting activity with no significant effect on overall firing rate. The data suggest that: (1) interneuronal firing, during the hippocampal theta rhythm, is dominated by an excitatory cholinergic input and not by excitatory collaterals of pyramidal cells; and (2) somatic burst firing by CA1 pyramidal cells requires the presence of acetylcholine. PMID- 1446224 TI - Expression of the non-proliferation-specific protein, statin, in grey matter neuroglia of the aging rat brain. AB - The monoclonal antibody, S-44, identifies statin, a 57 kDa nuclear protein which appears to be expressed exclusively in non-proliferating cells. We previously demonstrated that in the aging rat corpus callosum approximately one third of neuroglia are statin-negative, suggesting the existence of an unexpectedly large cycling glial compartment. In the present study, double-labeling of individual cultured astroglia with [3H]thymidine and the S-44 antibody provided direct evidence for the non-proliferative status of statin-positive cells. The S-44 antibody was used to immuno-localize statin and thereby determine growth fractions for neuroglia in various grey matter regions of 3-, 18-, and 33-month old rats. The proportion of statin-negative (cycling) cells for the three ages combined ranged from about 24% in the molecular layer of the dentate gyrus to 38% in the molecular layer of the parietal cortex. In most regions surveyed total glial counts and proportions of statin-positive and -negative cells did not vary significantly as a function of advancing age. These results suggest that (i) as in corpus callosum, pools of cycling neuroglia in various grey matter regions are far in excess of those previously predicted by S-phase labeling with [3H]thymidine or BUdR, and (ii) ratios of proliferating-to-quiescent neuroglia are tightly regulated over much of the animal's adult life span. These conserved ratios may be used as markers of normal CNS senescence, and deviations thereof may indicate the presence and extent of intervening neuropathologic processes. PMID- 1446225 TI - Effect of pentobarbital on cerebral regional venous O2 saturation heterogeneity. AB - Observed venous O2 saturation inhomogeneity in the brain implies a microregional imbalance in O2 supply/consumption. We hypothesized that this heterogeneity should be decreased by pentobarbital anesthesia through a reduction in regional metabolic heterogeneity. Male, Long-Evans, approximately 350 g rats were either anesthetized with 50 mg/kg pentobarbital (n = 10) or used as a conscious control group (n = 10, catheters inserted two hours earlier under ether anesthesia). In each rat, regional cerebral blood flow was determined by [14C]iodoantipyrine and regional arterial and venous O2 saturation were determined by microspectrophotometry. In the PB group, the mean blood pressure (107 +/- 7 Torr), heart rate (362 +/- 29/min), average cerebral blood flow (63 +/- 19 ml/min/100 g), and average cerebral O2 consumption (3.7 +/- 1.2 ml O2/min/100 g) were lower than those values in the conscious group (128 +/- 15, 474 +/- 44, 112 +/- 40, and 7 +/- 3), respectively. O2 extraction did not change after pentobarbital anesthesia. However, the dispersion of venous O2 saturation narrowed. The distribution of O2 saturations in 373 cerebral veins of anesthetized rats had a significantly reduced coefficient of variation [C.V. = 100 x (S.D./mean) = 13] as compared to a C.V. of 18 in 320 veins in conscious rats. Thus, pentobarbital anesthesia reduced the microregional venous O2 saturation inhomogeneity in the brain, creating a more uniform balance of oxygen supply and consumption. PMID- 1446226 TI - Extracellular dopamine in the rat striatum during ischemia and reperfusion as measured by in vivo electrochemistry and in vivo microdialysis. AB - The effects of transient global forebrain ischemia and reperfusion on striatal extracellular dopamine levels were analyzed using both in vivo electrochemistry and in vivo microdialysis in urethane-anesthetized rats. Electrochemical records showed that extracellular dopamine levels increased once during the period of ischemia, and a second time during reperfusion. This biphasic pattern was not detected by microdialysis, probably because of the relatively low time resolution of this technique. Microdialysis provided evidence that the voltammetric signal was a measure of dopamine, and also allowed measurement of the metabolites dihydroxyphenylacetic acid and homovanillic acid, both of which decreased during ischemia. The biphasic dopamine pattern seen in rats is similar to that reported previously in gerbils, suggesting that it is a phenomenon common to transient ischemia and reperfusion across different species and models of transient global ischemia. This phenomenon may have important implications for therapeutic intervention in cerebral ischemia. PMID- 1446227 TI - Role for protein synthesis in the neurotoxic effects of methamphetamine in mice and rats. AB - The mechanism by which the amphetamines damage selectively nigrostriatal dopaminergic neurons in experimental animals remains uncertain. The observation that neuronal cell death during embryogenesis involves an activation of gene expression and new protein synthesis, coupled with recent reports indicating that the amphetamines are capable of inducing neuropeptide biosynthesis, offers a possible clue as to their neurotoxic mechanism of action. Based on these considerations, we evaluated the effects of two different inhibitors of protein synthesis, cycloheximide and anisomycin, on the long-term, amine-depleting effects of methamphetamine (METH) in mice and rats. Both inhibitors were found to block the amine-depleting effects of METH in these species. In other experiments, cycloheximide did not affect the functional integrity of dopaminergic or glutamatergic neurons, transmitter systems previously implicated in the neurotoxic mechanism of action of METH. These findings raise the possibility that the neuronal-damaging effects of METH are mediated via a synthesis of 'neurotoxic' proteins. PMID- 1446228 TI - Post-ischemic administration of bifemelane hydrochloride prohibits ischemia induced depletion of the muscarinic M1-receptor and its mRNA in the gerbil hippocampus. AB - Parallel determinations of muscarinic cholinergic M1 receptor (M1-R) binding and of M1-R mRNA levels were carried out in the gerbil hippocampus 14 days after 5 min of transient ischemia. Both were reduced in the ischemic tissue to about 50% of the levels found in sham-operated controls, indicating that the late loss of M1-R is probably dependent on decreased synthesis. Three administrations of bifemelane hydrochloride (15 mg/kg, i.p., just after ischemia and 6 and 12 h later) completely prevented neuronal death in the hippocampus and ischemia induced losses of hippocampal M1-R and its mRNA. Since vascular dementia may depend upon the ischemia-induced losses in cholinergic communication in the hippocampus, these findings suggest that it may be possible to prevent its occurrence by post-ischemic treatment with bifemelane hydrochloride. PMID- 1446229 TI - Non-photic phase shifting of the circadian activity rhythm of Syrian hamsters: the relative potency of arousal and melatonin. AB - This study investigated the relative potency of melatonin and arousal as Zeitgebers in the non-photic phase shifting of circadian rhythmicity in the adult Syrian hamster. Animals held under dim red light (DD) exhibited robust free running rhythms of wheel-running activity. Melatonin (1 mg/kg) or ethanolic saline vehicle, delivered manually by subcutaneous injection after removing the animal from its cage, resulted in phase advances of the activity rhythm. This effect was phase dependent, injections at CT 8 and 10 being effective (CT 12 = anticipated activity onset), whereas injection at CT 2, 6, 14 and 20 did not cause a shift. There was no significant difference between the magnitude or timing of phase shifts in response to injections of saline or melatonin. To determine whether the observed shifts were related to arousal of the animals induced by handling, a second group held under DD were fitted with chronic s.c. cannulae so that melatonin solution or vehicle could be delivered remotely at projected CT 10. Neither solution had any effect upon the free-running rhythm. However, when these animals received manual s.c. injection of saline or melatonin solution, they exhibited phase advances similar to those observed in Expt. 1. These results fail to support the hypothesis that melatonin can exert a chemically specific, acute phase-shifting action in the adult Syrian hamster. They do, however, demonstrate the potent effect of arousing stimuli upon the circadian clock in this species. PMID- 1446230 TI - Ca(2+)-dependent release of [3H]GABA in cultured chick retina cells. AB - Depolarization by K+ (50 mM) of cultured chick retina cells released 1.14 +/- 0.28% of the accumulated [3H] gamma-aminobutyric acid (GABA) in the absence of Ca2+, but when 1.0 mM Ca2+ was present, the internal free calcium ion concentration [Ca2+]i rose by about 750 nM and the [3H]GABA release about doubled to a value of 2.22 +/- 0.2% of the total [3H]GABA. Nitrendipine (0.1 microM), a blocker of the L-type Ca2+ channels, blocked the [Ca2+]i response to K+ depolarization by about 65%, and the omega-Conotoxin GVIA (omega-CgTx) (0.5 microM), a blocker of the N-type of Ca2+ channels, inhibited by 27% the [Ca2+]i rise due to K+ depolarization. Parallel experiments showed that nitrendipine inhibits [3H]GABA release to the level observed in the absence of Ca2+, whereas omega-CgTx did not inhibit significantly the release of [3H]GABA. The results also show that the release of [3H]GABA due to K(+)-depolarization in the absence of Ca2+ can be totally blocked by 1-(2-(((Diphenylmethylene) amino)oxy)ethyl) 1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (NNC-711), an inhibitor of the GABA carrier. However, in the presence of Ca2+, NNC-711 blocks the release only by about 66%, corresponding to the Ca(2+)-independent release. Thus, it is concluded that [3H]GABA is released in chick retina cells by the exocytotic mechanism, which is Ca(2+)-dependent, and by reversal of the carrier, which is Ca(2+)-independent, in much the same way as has been found for other GABAergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446231 TI - Topographical analysis of epileptiform potentials in rat somatosensory cortex: the interictal to ictal transition. AB - Large quantities of penicillin were applied to the face and forelimb region of rat somatosensory cortex, producing an epileptic focus with both electrographic and behavioral signs of seizures that regularly repeated over a period of several minutes. Epicortical potentials were recorded simultaneously from a 64 channel micro-electrode array (8 x 8 platinum electrodes) with inter-electrode distances of 0.5 mm, covering a 3.5 x 3.5 mm2 area centered on the penicillin injection site. Cluster analysis was used to classify successive epileptiform discharges into interictal, transitional, and ictal groups. Principal components analysis (PCA) was used to extract fundamental waveforms producing the spike complex in each group, and to estimate the locations and spatial extent of neuronal populations participating in epileptiform discharge. During all states of epileptic excitability, it was possible to account for over 90% of the variance in the epicortical potential waveforms using a model with only two spatially overlapping populations of cells. The location and spatial extent of the populations remained unchanged by the transition to seizures; the interictal and ictal states were distinguished only by changes in the timing and amplitude of potentials in the two putative neuronal populations. The present model, using only two stationary neuronal populations to reproduce all spatiotemporal patterns in the neocortical epileptogenic focus, is compared to models proposed by others in which epileptic discharge is thought to propagate sequentially through adjacent cortex. It is concluded that the initiation, maintenance, and termination of seizures in neocortex relies on mechanisms that are not necessarily reflected in changes in spatiotemporal interactions among epicortically recorded cell groups within the focus. These mechanisms may be distinguished from those responsible for the spread of seizures within neocortex. PMID- 1446232 TI - Anatomical evidence for genetic differences in the innervation of the rat spinal cord by noradrenergic locus coeruleus neurons. AB - Pontospinal noradrenergic neurons located in the A5, A6 (locus coeruleus, LC), and A7 cell groups are the major source of the noradrenergic innervation of the spinal cord. We have recently examined the specific terminations of these three cell groups in the spinal cord and found that the LC provides the major noradrenergic innervation of the ventral horn, while the A7 and A5 cell groups innervate the dorsal horn and intermediate zone, respectively. However, the results of similar experiments from another laboratory have shown that noradrenergic neurons in the locus coeruleus primarily innervate the dorsal horn, while the A5 and A7 innervate the intermediate zone and the ventral horn. These conflicting results may be due to fundamental genetic differences between the rats used in our experiments (Sasco Sprague-Dawley) and those used by the other laboratory (Harlan Sprague-Dawley). This possibility was examined by determining the projections of coeruleospinal neurons in these two rat substrains using the anterograde tracer Phaseolus vulgaris leucoagglutinin. The results indicate that in Sasco rats the LC neurons project through the ipsilateral ventromedial funiculus and terminate almost exclusively in the medial part of laminae VII and VIII, the motoneuron pool of lamina IX, and lamina X. In contrast, LC neurons in Harlan rats project bilaterally through the superficial dorsal horn and the dorsolateral funiculus and terminate most heavily in dorsal horn laminae I-IV. In addition, the LC neurons of Sasco rats innervate cervical spinal cord segments more densely than lumbar spinal cord segments, while in Harlan rats the lumbar spinal cord is more densely innervated than the cervical spinal cord. These results indicate that the projections of coeruleospinal neurons in Sasco rats are fundamentally different from those in Harlan rats and suggest that noradrenergic LC neurons may have different physiological functions in these two rat substrains. PMID- 1446233 TI - Muscimol infused into the medial septal area impairs long-term memory but not short-term memory in inhibitory avoidance, water maze place learning and rewarded alternation tasks. AB - These experiments investigated the effects of injections of muscimol (1 or 5 nmol), administered into the medial septal area prior to training, on memory tested at different retention delays after training in 3 tasks: an inhibitory avoidance task, a one-trial place learning task, and a rewarded alternation task. In all 3 tasks, intraseptal injections of muscimol did not impair memory performance at short retention delays, but impaired memory at the longer retention delays. These findings are consistent with the view that GABAergic regulation of the septohippocampal cholinergic system plays a selective role in the establishment of long-term memory. PMID- 1446234 TI - gamma-Aminobutyric acid immunoreactive structures in the nucleus tractus solitarius: a light and electron microscopic study. AB - gamma-Aminobutyric acid immunoreactive perikarya and boutons in the nucleus tractus solitarius of the cat were examined at both the light and electron microscopic level. Immunoreactive neurones were found predominantly in the parvocellular subdivision of the nucleus tractus solitarius and to a lesser degree in all the other subdivisions of the nucleus tractus solitarius and the dorsal vagal motonucleus. All the immunoreactive perikarya observed were similar in size and morphology. gamma-Aminobutyric acid immunoreactive boutons were observed throughout the nucleus tractus solitarius. However, in contrast to its high content of immunoreactive perikarya the parvocellular subdivision contained the lowest density of immunoreactive boutons. Ultrastructural examination of immunoreactive boutons in the different regions of the nucleus tractus solitarius revealed that they formed synaptic specializations, predominantly with dendritic shafts, all of which were of the symmetric type. This pattern of innervation was observed throughout the medial, commissural, ventrolateral and parvocellular subdivisions of the nucleus tractus solitarius. PMID- 1446235 TI - Medullary respiratory neurons in the guinea pig: localization and firing patterns. AB - The location and firing patterns of medullary respiratory neurons have been described in a small number of species. The cat has been the most widely studied species, but some potentially important differences have recently been noted in others. A more complete survey of species is required to determine the significance of these differences. We describe the location and firing patterns of respiratory neurons in the medulla of anesthetized, paralyzed and mechanically ventilated adult guinea pigs. Extracellular single-unit recordings were made from the medulla, their phase relationship with phrenic nerve activity used to define them as respiratory and their location marked with fast green. Respiratory units were concentrated ventrolateral to the nucleus tractus solitarius (NTS) and within and surrounding the nucleus ambiguus (NA), corresponding to the dorsal respiratory group (DRG) and ventral respiratory group (VRG) of the cat, respectively. Most DRG respiratory units were inspiratory, while the VRG contained equal numbers of inspiratory and expiratory units. The DRG and VRG both contained early, late and constant-frequency inspiratory and expiratory units. In general, these findings are similar to those in other mammalian species examined, consistent with these basic aspects of the respiratory network being highly conserved. PMID- 1446236 TI - Characterization of interleukin-1 production by microglia in culture. AB - The production of interleukin-1 (IL-1) by cultured neonatal rat microglia was studied using the D10 cell assay. The results show that IL-1 was secreted in response to lipopolysaccharide (LPS) in a dose- and time-dependent fashion. IL-1 production was specific to microglia and was not induced in astrocytes. Indomethacin, which is known to modulate the release of IL-1 from monocytes, had no effect on LPS-stimulated microglia. Aging of the microglia from two weeks to 4 weeks in culture, however, reduced the release of IL-1 in response to LPS. Our data indicate that microglia are a major source of IL-1 and that the release of IL-1 depends on the presence of inflammatory mediators such as LPS and the age of the culture. PMID- 1446237 TI - Distribution and relative density of p75 nerve growth factor receptors in the rat brain as a function of age and treatment with antibodies to nerve growth factor. AB - It is clear that nerve growth factor (NGF) has a role in the central nervous system. In order to begin to determine the possible roles of NGF in the CNS, neonatal rats were given daily subcutaneous injections of antibodies to NGF (ANTI NGF) beginning at birth for a period of one month. By utilizing the monoclonal antibody, 192-IgG, which recognizes the p75 NGF receptor (NGFR), and standard immunohistochemical techniques we have localized p75 NGFR in variously aged ANTI NGF-treated animals and compared the anatomic localization and relative density of the p75 NGFR immunoreactive (p75 NGFR-I) regions to same age untreated and preimmune sera-treated littermates. We confirm previously reported localizations of p75 NGFR-I in the rat brain. In addition, we demonstrate that p75 NGFR-I levels of ANTI-NGF-treated rats found in the molecular, the granular and the Purkinje cell layers of the cerebellum, the vestibular nuclei, the spinal tract of V and the cochlear nuclei remain at lower concentrations compared to same-age control animals. We also demonstrate that p75 NGFR-I levels in the basal nucleus approaches background levels after ANTI-NGF treatment. We hypothesize that ANTI NGF biologically inactivates NGF, which over a period of 30 days results in decreased p75 NGFR-I. These results are consistent with neuronal loss in these regions following ANTI-NGF treatment. Furthermore, the immunological methods used to produce the specific deficits in the present study may have broader implications with respect to usefulness as a method for determining the dependency of CNS neuronal populations for a putative neurotrophic factor and as a method for the development of models of neurodegenerative diseases. PMID- 1446238 TI - Effect of chronic treatment with recombinant interleukin-2 on the central nervous system of adult and old mice. AB - We have studied the effects of chronic treatment with recombinant interleukin-2 on the central nervous system of adult and old mice. Treatment with high doses of recombinant interleukin-2, on a schedule similar to that used in humans, was started at the age of 4 and 17 months, respectively, and ended 3 months later. At that time, all the mice were tested for acquisition of a passive-avoidance task and then sacrificed for histological examination. Three of the four groups (treated and control adults and control old mice) did not differ from one another in task performance or neuron density in frontal cortex, cerebellum, dentate gyrus or CA1-2, CA3, CA4 hippocampal areas. The old treated mice were unique in showing impairment of the mnesic functions and marked neuronal cell loss and degenerative changes limited to the hippocampal regions. Immunohistochemical studies did not show any significant amount of immunoglobulins in affected areas. Our results suggest that in old mice the impairment of the mnesic functions after recombinant interleukin-2 administration is due to hippocampal neuronal damage. PMID- 1446239 TI - The physiological effects of serotonin are mediated by the 5HT1A receptor in the cat's cerebellar cortex. AB - Serotonin is present in a fine beaded plexus in the cerebellar cortex of several mammalian species. In the cat, serotoninergic afferents arise from neurons located within the lateral, paramedian and peri-olivary reticular nuclei (Kerr and Bishop, J. Comp. Neurol., 304 (1991) 502-515). In addition to serotoninergic afferents, these same nuclei also contain a separate population of neurons that give rise to mossy fibers to the cerebellar cortex. Physiological studies have shown that mossy fibers are excitatory to their target neurons. The intent of the present study was to determine the physiological effects of serotonin in the cat's cerebellum in an in vivo preparation and to identify the receptor(s) that mediate the observed responses. Iontophoretic application of serotonin (5HT) onto Purkinje cells reduces the spontaneous firing rate of all cells tested (n = 12). Serotonin also blocks the excitatory effects elicited by the application of aspartate in 17 of 19 units tested and of glutamate (n = 62) in all cases. In addition, 5HT potentiated the inhibitory action of GABA (n = 12). Iontophoretic application of the 5HT1A agonists, 8-OH-DPAT and ipsapirone, mimic the suppressive action of serotonin in a dose-dependent manner. This response, as well as the 5HT mediated suppression are blocked by the application of spiperone, a 5HT1A antagonist. Compounds selective for the 5HT1C,2 and 3 receptors are physiologically ineffective. The present data are in partial agreement with previous studies in the rat's cerebellar cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446240 TI - bFGF promotes the survival of entorhinal layer II neurons after perforant path axotomy. AB - Infusion of basic fibroblast growth factor (bFGF) prevents the loss of cholinergic neurons in the septum/diagonal band of broca following fimbria-fornix transection. However, an in vivo test of whether bFGF will also rescue injured non-cholinergic or cortical neurons has not been carried out. Previous studies have shown that the majority of layer II stellate neurons utilize an excitatory amino acid as their neurotransmitter. In order to determine if bFGF acts on non cholinergic cortical neurons, a paradigm was developed to examine whether or not bFGF could spare layer II entorhinal stellate cells from axotomy induced death or atrophy. Axotomy of the medial entorhinal cortex fibers projecting to the dentate gyrus of the hippocampal formation via the perforant path lead to retrograde cell loss in entorhinal cortex. Fourteen or thirty days after a unilateral knife cut axotomy of the perforant path, layer II of medical entorhinal cortex showed a 28% decrease in large stellate neurons as well as many weakly stained, hollow cells compared to the non-lesioned side or naive controls. Layer IV neurons, however, which do not project via the perforant path, showed little detectable change in the number of cells ipsilateral to the knife-cut as compared to the contralateral side. Intraventricular infusion of bFGF over a period of 14 days reduced the 28% cell loss to less than 6%. Thus, bFGF is capable of preventing cortical neuronal loss and/or atrophy associated with retrograde degeneration of non-cholinergic neurons following axotomy. PMID- 1446241 TI - Effect of starvation on glycogen and glucose metabolism in different areas of the rat brain. AB - We have studied the changes in concentration of glycogen, glucose and the bisphosphorylated sugars, glucose 1,6-P2 and fructose 2,6-P2, in several rat brain regions during 72 h of starvation. The animals were killed by focused microwave irradiation. The activities of glycogen metabolizing enzymes in the different areas were measured. A large decrease in glycogen and glucose concentration was observed in all areas. The concentrations of bisphosphorylated sugars changed, suggesting that an increase in glycolysis could take place at the beginning of starvation, with blood glucose as a major energy source. Differences in metabolite concentration before starvation disappeared after 72 h. The activities of glycogen synthase, glycogen phosphorylase and glycogen phosphorylase kinase were similar in all areas, and they did not change during starvation. PMID- 1446242 TI - Identification of a sexually dimorphic neural population immunoreactive for calcitonin gene-related peptide (CGRP) in the rat medial preoptic area. AB - The medial preoptic area (MPOA) of the rat exhibits morphological sex differences and is implicated in sex-specific functioning and behaviour. Using immunocytochemistry, the distribution and numbers of cells containing calcitonin gene-related peptide (CGRP) were examined in the MPOA of adult male and female rats. In the intact female rat, CGRP-immunoreactive (-IR) cells were found in a continuum within the MPOA extending from the caudal aspects of the organum vasculosum of the lamina terminalis through the anteroventral periventricular nucleus (AVPv) to the region of the medial preoptic nucleus (MPN). An additional small group of CGRP-IR cells was noted at the level of the caudal MPNin the ventrolateral (VL) region. Compared with males, the AVPv and MPN regions of the female contained over 25-fold more CGRP-IR cells (P < 0.01). The VL region contained similar numbers of CGRP-IR cells in both sexes. Ovariectomy 1 month earlier, with or without subsequent 17-beta estradiol treatment, had no effect on the numbers or distribution of CGRP-IR cells in the MPOA. Gonadectomy of male rats resulted in a significant increase (P < 0.01) in the numbers of CGRP-IR cells in the AVPv and MPN regions. Subsequent administration of testosterone propionate for 1 week reduced (P < 0.05) numbers of CGRP-IR cells to levels observed in the intact male. Neurones containing CGRP in the VL group were not altered by gonadal steroid manipulation. This study shows that CGRP neurones in the AVPv/MPN region are sexually dimorphic.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446243 TI - Lesions of the medial septum which produce deficits in working/spatial memory do not impair long-term potentiation in the CA3 region of the rat hippocampus in vivo. AB - The effects of removing the septohippocampal pathway on the ability to induce long-term potentiation (LTP) in the CA3 region of the hippocampus was examined in vivo in rats. The septal input to the hippocampus was destroyed by electrolytic lesioning of the medial septum (MS). Prior to electrophysiological investigation, working/spatial memory of lesioned and control rats was tested using an 8-arm radial maze task. Maze performance was significantly impaired in animals with MS lesions. LTP inducibility was examined in the commissural fimbrial fibre- and mossy fibre (mf)-CA3 pathways in MS-lesioned and control rats. The pre-tetanus values in MS-lesioned rats tended to be smaller than those in controls, in both pathways. High-frequency stimulation of the commissural fibres resulted in a sustained increase in the orthodromic population spike and EPSP amplitude in both control and MS-lesioned rats. The magnitude of potentiation was similar in both groups. In control rats, high-frequency stimulation of the mf potentiated the amplitude of both the population spike and EPSP; in MS-lesioned rats, the EPSP amplitude alone was significantly increased by mf high-frequency stimulation. Hippocampal acetylcholinesterase (AChE) content was severely reduced bilaterally in MS-lesioned rats with working/spatial memory impairments, indicating that the lesions were effective in destroying the cholinergic septohippocampal input. These findings suggest that, in contrast to working/spatial memory processes, LTP at CA3 synapses is not dependent upon the integrity of the septohippocampal pathway. PMID- 1446244 TI - Plasticity of GABAergic terminals in Deiters' nucleus of weaver mutant and normal mice: a quantitative light microscopic study. AB - This study reports on the developmental changes in size and the average density of GABAergic axonal boutons bordering on the somata of large neurons in the dorsal part of the lateral vestibular nucleus (Deiters' nucleus) in normal and mutant mice. Weaver mutants, PCD mutants and the corresponding wild types were used to test for size alterations and differences in the number of GABA immunopositive terminals. Hemicerebellectomized animals were examined in addition. Quantification of bouton profile size was performed from 30-microns thick vibratome and 0.5-micron Araldite-embedded semi-thin sections immunoreacted for GABA from 7 days postnatally up to an age of 9 months. Terminal density was determined at the 5-6 month stage from semi-thin sections only. Morphometric analysis over the lifetime of normal animals (B6CBA) revealed a progressive increase in the size of bouton profiles, which peaked at 5-6 months and reached sizes of 2-3 microns2. In weaver mutants a parallel development in terminal size was found to be present, but the size of the largest terminals exceeded those of the controls by 75-100%, reaching 3-6 microns2 with the same time course. PCD mutants, with an almost total absence of Purkinje cells had, on the contrary, small bouton profiles that reached a maximum of only 2 microns2. The hemicerebellectomized animals responded with decreased bouton profile size ipsilaterally. The terminal numbers per unit membrane length were surprisingly similar in wild types and weaver mutants, despite a reduction in Purkinje cells of almost 50% in the weaver anterior lobe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446245 TI - Cortical neurons inhibit basal and interleukin-1-stimulated astroglial cell secretion of nerve growth factor. AB - Primary cultures of neonatal rat cortical neurons and astrocytes synthesize and secrete nerve growth factor (NGF). Co-culturing neurons with astrocytes decreased NGF secretion in the co-cultures. The inhibition of co-culture NGF secretion was partially reversible upon selectively decreasing the number of neurons by glutamate treatment. Interleukin-1 beta (IL-1) stimulated NGF secretion from astrocytes, and the magnitude of this secretion was decreased in the co-cultures. Thus, co-culture with neurons decreases astroglial cell secretion of NGF and down regulates astroglial responsiveness to IL-1. PMID- 1446246 TI - Octopamine selectively modifies the slow component of sensory adaptation in an insect mechanoreceptor. AB - The effects of octopamine were studied on the dynamic behavior of the sensory neuron in the cockroach femoral tactile spine. The neuron is a rapidly adapting mechanoreceptor in which adaptation occurs by elevation of the threshold for action potential encoding. The threshold follows increases or decreases of membrane potential, with a delay that involves two separate exponential components. Previous evidence has associated the slow component with sodium pumping and the fast component with sodium channel inactivation. Octopamine reversibly raised the resting threshold and increased but slowed the slow component. These data indicate that octopamine has specific effects on membrane ionic processes in insect sensory neurons. PMID- 1446247 TI - Dynamic analysis of drug action on in vitro reconstituted thyroid follicle by microinjection of tracer molecules and videomicroscopy. AB - Thyroid cells isolated from the gland by trypsinization are capable in culture of reconstituting histiotypic structures, the thyroid follicles. This morphological differentiation requires the presence of the main thyroid regulator; thyrotropin. We have analyzed some structural and functional aspects of in vitro reconstituted thyroid follicles (RTF) using microinjection of fluorescent probes and videomicroscopy. This experimental approach allowed to visualize biological processes and actions of drugs, signalling factors, etc. in living cells. We describe here some examples of what can be studied with this powerful still undervalued method. Microinjection of a cell-impermeant fluorescent probe of either high or low molecular mass into the lumen of RTF allowed to check the tightness of this compartment and therefore to analyze the control of tight junctions assembly. A small cell-impermeant probe like Lucifer Yellow microinjected into a cell was used to demonstrate and then to study the regulation of cell to cell communication via gap junctions. The presence of calcium in the lumen of RTF was detected by microinjection of a properly designed probe: Calcium Green which becomes fluorescent in the presence of the ligand. The lumen to cell transport or endocytosis of thyroglobulin, the thyroid prohormone, which is stored into the lumen of the follicles, is currently studied by microinjection of TRITC-labeled thyroglobulin. Coupled to image processing and videorecorder systems, kinetic analysis and quantitative measurements can be performed. PMID- 1446248 TI - Neural cells in culture: models for the purification and the study of the effects of growth factors. PMID- 1446249 TI - Neurotoxicity of macrophages infected by HIV1. PMID- 1446250 TI - Short-term in vitro and in vivo bioassays: their role in estimating the toxic potential of inhaled complex mixtures for humans. PMID- 1446251 TI - Use of mesothelial cell cultures to assess the carcinogenic potency of mineral or man made fibers. AB - Natural mineral fibers may produce pulmonary cancers and mesothelioma. In contrast with lung cancer, the incidence of fiber-induced mesothelioma is not enhanced in smokers compared to non smokers. It is therefore of special interest to use mesothelial cells to study the toxicity of natural or man made mineral fibers. Several years ago, we have developed a method to culture rat pleural mesothelial cells (RPMC). We have first studied the effects of asbestos fibers by the application of in vitro tests formerly developed to determine the genotoxicity and transforming potency of soluble xenobiotics. Moreover, we have determined whether RPMC expressed cytochromes P450 known to metabolize polycyclic aromatic hydrocarbons. This paper reviews the results obtained so far. It has been found that asbestos fibers produced a cell transformation and a genotoxicity characterized by the formation of aneuploid cells, abnormal anaphases, chromosomal aberrations and DNA repair (UDS). In addition, RPMC expressed different forms of cytochromes P450. It is nowadays suggested that the tumorigenic potency of asbestos fibers may be related to the fiber dimensions, to their surface properties and in vivo biopersistence; this term involves the fiber solubility in biological medium and the fiber epuration from the lung by clearance mechanisms. Experiments are now in progress to determine whether the in vitro effects are dependent on the fiber parameters suggested as playing a role in the carcinogenic potency. PMID- 1446252 TI - Tracheal epithelium in culture: a model for toxicity testing of inhaled molecules. AB - Rabbit trachea primary cultures have been developed as a model to evaluate the toxicity of noxious airborne pollutants. A mucociliary epithelium has been restored in vitro on collagen gel. Several general cytotoxicity assays (viability and growth inhibition) permit a first assessment for the acute toxicity of the tested molecules. More specific criteria such as measurement of the integrity of the epithelial barrier and inhibition of ciliary beat frequency allow to determine a specific impact of xenobiotics on the mucociliary epithelium in culture. PMID- 1446253 TI - In vitro study of gas effects on alveolar macrophages. AB - To evaluate the biological effects of gas pollutants on alveolar macrophages several in vitro systems have been developed. We described here an original method of cell culture in aerobiosis, which permitted direct contact between the atmosphere and the target cells. We studied the long term (24 h) and short term (30 min) effects of NO2 on alveolar macrophages. Our results demonstrated that exposure of alveolar macrophages to gas pollutants may be responsible for either cell injury or cell activation associated with the release of various bioactive mediators (superoxide anion, neutrophil chemotactic activity). Cell culture in aerobiosis opens new ways for the research on the biological effects of gas pollutants. PMID- 1446256 TI - Perifusion system: its use in the study of the neuroendocrine control of human pituitary tumoral cells. PMID- 1446254 TI - Receptors and transduction mechanisms in anterior pituitary: primary cultures, transfected clonal cells and human tumor derived cells. PMID- 1446255 TI - Hypophyseal cells model systems: the "GH" rat tumor-derived cell lines as a tool for the study of gene expression. PMID- 1446257 TI - The Sertoli cell in vivo and in vitro. AB - The Sertoli cell extends from the basement membrane of the seminiferous tubule towards its lumen; it sends cytoplasmic processes which envelop different generations of germ cells. The use of Sertoli cell culture began to develop in 1975. To reduce germ cell contamination immature animals are generally used as Sertoli cell donors. Sertoli cell mitosis essentially occurs in sexually immature testes in mammals; mitosis of these cells is observed in vitro during a limited period of time. Sertoli cells in vivo perform an impressive range of functions: structural support of the seminiferous epithelium, displacement of germ cells and release of sperm; formation of the Sertoli cell blood-testis barrier; secretion of factors and nutrition of germ cells; phagocytosis of degenerating germ cells and of germ cell materials. Some of the Sertoli cell functions can be studied in vitro. The recent development of Sertoli cell culture on permeable supports (with or without extracellular matrix) has resulted in progress in understanding the vectorial secretion of several Sertoli cell markers. In addition to FSH and testosterone, several other humoral factors are known to influence Sertoli cell function. Furthermore, myoid cells bordering the tubules as well as germ cells are capable of regulating Sertoli cell activity. Sertoli cells are the most widely used testicular cells for in vitro toxicology. The testis is highly vulnerable to xenobiotics and radiations, yet the number of studies undertaken in this field is insufficient and should be drastically increased. PMID- 1446258 TI - Dual compartment (bicameral) culture: role of basement membrane in epithelial differentiation. AB - A number of years ago we reported that tight junctions between adjacent Sertoli cells subdivide the seminiferous epithelium into two compartments, basal and adluminal, thus forming the morphological basis of the blood-testis barrier. It is now generally believed that the special milieu created by the Sertoli cells in the adluminal compartment is essential for germ cell differentiation. In order to duplicate the compartmentalization that occurs in vivo, Sertoli cells were cultured in bicameral chambers on Millipore filters impregnated with a reconstituted basement membrane. Confluent monolayers of these cells were tall columnar (40-60 microns in height) and highly polarized. These Sertoli cell monolayers established electrical resistance that peaked when the Sertoli-Sertoli tight junctions developed in culture. In addition, the monolayers formed a permeability barrier to 3H-inulin and lanthanum nitrate. The bicameral chambers were utilized in a number of studies on protein secretion, and it was revealed that numerous proteins are secreted in a polarized manner. In another study, hormone-stimulated aromatase activity was measured in Sertoli cells grown on plastic culture dishes, plastic dishes coated with laminin or Matrigel, and in the bicameral chambers. Cell culture on basement membrane substrates decreased the FSH-dependent estrogen production. No estrogen production was observed when the Sertoli cells were cultured in the bicameral chambers. These results are in accord with the hypothesis that differentiated Sertoli cells lose their ability to metabolize androgen to estrogen in an hormone-dependent manner, whereas undifferentiated cells in culture, or in vivo, have a very active FSH-dependent aromatase activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446259 TI - Permeable collagen-glycosaminoglycan cross-linked copolymers for the study of biological responses of cocultured Sertoli and spermatogenic cells. AB - A novel collagen-glycosaminoglycan (C-GAG) substrate was developed to overcome the optical opacity of a HATF nitrocellulose substrate and to provide a more physiological permeable substrate for cocultured Sertoli and spermatogenic cells. Cocultures were prepared on optically transparent C-GAG discs attached to a polyester mesh to facilitate handling. Sertoli cells displayed a cuboidal-to columnar shape; a large number of spermatogonia and primary spermatocytes connected by intercellular bridges were associated with basolateral and apical surfaces of Sertoli cells up to 12 days after plating. Rat Sertoli-spermatogenic cell cocultures have been used for testing the effect of toxicants on rat spermatogenesis in vitro. In our initial studies, we tested the effects of the toxicant gossypol on spermatogenic cells cocultured with Sertoli cells on non permeable (plastic) and permeable substrates (HATF nitrocellulose) under both standard culture conditions and during perifusion after achieving a continuous electrical-resistant cell monolayer. A selective mitochondrial structural damage was observed in spermatogenic cells (spermatogonia and spermatocytes) but not in the coexisting Sertoli cells. This damage was time- (15-60 min) and dose dependent (0.1-10 microM) and developed more rapidly under perifusion conditions. Similar mitochondrial damage was reported in the intact animal but required higher concentrations (mg) and longer administration time (months) for detection. Studies are in progress to evaluate the effect of additional toxic chemical agents on functional properties of Sertoli and spermatogenic cells in cocultures prepared on various classes of C-GAG substrates. PMID- 1446260 TI - The paracrine role of Sertoli cells on Leydig cell function. PMID- 1446261 TI - Endocrine cell excitability opens the way to novel pharmacological intervention: example of the anterior pituitary cell. PMID- 1446262 TI - Hormonogenesis in thyroid cells cultured on porous bottom chambers. AB - Different processes implied in thyroid hormonogenesis (thyroglobulin, thyroperoxidase and hydrogen peroxide generating system expressions) and their regulation by TSH and iodide have been studied using porcine thyroid cells cultured in porous bottomed chambers. This system allowed to reproduce the functional bipolarity. Cells form a tight and polarized monolayer. Both apical and basolateral poles of epithelial cells were independently accessible and the cell layer separated two compartments which can contain different media. A major polarized secretion of thyroglobulin into the apical compartment was observed; it was increased in the presence of TSH as well as the thyroglobulin synthesis and mRNA level. These TSH effects were the consequence of adenylcyclase stimulation. Active transport of iodide, iodination of thyroglobulin and hormonosynthesis took place only in the presence of TSH. These steps occurred at the apical pole of cells. In the culture chamber system, thyroglobulin was weakly iodinated (6 atoms of iodide per mole of thyroglobulin; in vivo up to 40 atoms per mole) but hormonogenesis efficiency was close to this one observed in vivo (40%). Iodide concentrations higher than 0.5 microM daily added to the basal medium inhibited iodination of thyroglobulin and hormonosynthesis. Some components contained in culture media were inhibitors for iodination when they were present in the apical medium such as vitamins, amino acids and phenol red. The culture system appears to be interesting for pharmacological and toxicological studies. PMID- 1446263 TI - Genetic influences on reproductive performance. AB - The potential for genetic improvement of reproductive performance in pigs is great. Improvement can be achieved by increased commercial use of F1 hybrid females produced by crossing lines with excellent reproductive performance and by selection within nucleus populations of these lines for improved reproduction as well a for growth and carcass characteristics. The value of incorporating reproductive traits in selection programs is critically dependent on the relative economic values of fat (or lean) and of extra pigs produced. There is widespread agreement that litter size is the first choice as both the selection objective and the criterion to improve reproductive performance, on economic, genetic, and ease of measurement grounds. Although there are few examples of successful response to selection for increased litter size in pigs (exceptions being the University of Nebraska selection experiment and results achieved by hyperprolific selection schemes), overall results do not suggest that selection for litter size is impossible, only that it is difficult with limited resources. Artificial insemination is being used increasingly by pig breeding companies to accelerate rates of genetic improvement and to improve dissemination. Combining data from genetically connected herds and analyzing with BLUP computer programs to make efficient use of information on relatives makes selection for litter size feasible while maintaining selection pressure for growth and carcass traits. Although selection for lifetime productivity is impractical today, the knowledge and data accumulated from successful breeding programs for litter size may help make it the selection objective of the future. Meanwhile, the search continues for useful indirect criteria for selection, from testis size to molecular markers, and scientists are working with highly prolific breeds of Chinese pigs to better understand the physiologic and genetic basis of large litter size. PMID- 1446264 TI - Biosecurity and minimal disease herds. AB - The minimal disease concept is a way of raising pigs so that some specific diseases are absent. Many bacteria and viruses can be transferred by pigs, air, or mechanical contact. To avoid contamination, the herd location should take into consideration disease transmission possibilities. Herd health status and source herd health status should be continuously monitored. To maintain herd health status, specific rules need to be followed for herd construction and establishment, compound perimeter, people movement, down time, animal transportation, feed use and delivery, vehicle movement, material, dead animal disposition, and rodent control. All new incoming animals should go through quarantine, and in some herds, safer methods such as AI, embryo transfer, MEW, or hysterectomy and fostering need to be used. PMID- 1446265 TI - Breeding and gestation facilities for swine. Matching biology to facility design. AB - The rate-limiting phase of commercial swine production is breeding. The design of the breeding/gestation facilities influences the capacity of the producer to efficiently manage the breeding stock around the time of service and during the postservice period. Thus, breeding design potentially affects total born litter size and farrowing rates. In general, with original construction and facility renovation, the three principal activities of the breeding/gestation phase of production, (1) boar exposure/estrus detection, (2) breeding, and (3) gestation and pregnancy detection, should be independently considered. PMID- 1446266 TI - Factors affecting the reproductive performance of the weaned sow. AB - The majority of sows return to estrus within 2 weeks after weaning. Swine practitioners attempt to optimize production by reducing the WEI. Some sows fail to resume estrous cyclicity after weaning; however, the endocrinologic pathogenesis of these anestrous sows is speculative. The average WEI is influenced by numerous factors, including season, environmental temperature, photoperiod, nutrition, stress, facility design, lactation length, and management practices. It is evident that the majority of these factors have a more profound influence on primiparous sows than on multiparous sows. Optimum protein and energy consumption by sows during lactation and after weaning and effective utilization of breeding facilities reduce the WEI. The precise roles of photoperiodic changes, elevated environmental temperatures, and stress in seasonal infertility remain poorly understood. Fortunately, current management techniques have reduced the WEI on most farms without instituting therapeutic measures. PMID- 1446267 TI - Mating management. AB - The mating management of pigs is conducted under a wide spectrum of management techniques because females are variously hand-mated, pen-mated, or artificially inseminated. Factors that may affect the onset of estrus when hand-mating are boar exposure, method of housing females after weaning, season, type of facilities, and parity. The expression of sexual behavior in both male and female pigs can be influenced by a variety of physiologic, psychological, and environmental factors. To optimize the efficiency of estrous detection, females should not receive boar stimuli just prior to estrous detection when either hand mated or artificially inseminated. When females are pen-mated, management procedures need to be employed to prevent an excessive number of estrous females from accumulating, which leads to a decrease in boar fertility. PMID- 1446268 TI - Artificial insemination in swine. AB - This article analyses the advantages and disadvantages of artificial insemination with semen purchased from a center as well as from the herd boars on the farm. Intensive swine production could benefit greatly by adapting artificial insemination with herd boars, particularly from savings in labor and boar numbers. The techniques for semen collection, extension, and insemination are described, and sources for equipment given. Expected results of artificial insemination are quoted from experiments and international field experience. PMID- 1446269 TI - Optimizing longevity in sows and boars. AB - Longevity of sows and boars affects the productivity and economics of the herd. Implement a culling program that is tailored to the specific needs of the producer and the characteristics of the farm. Evaluate the removal policies regularly, estimate the longevity of breeding animals, calculate the nonproductive sow days associated with culling, and determine the major causes of culling and death. Once a longevity problem and its extent have been identified, the underlying problems and predisposing factors can be more easily corrected. PMID- 1446270 TI - Managing the lactating sow for optimal weaning and rebreeding performance. AB - Management of the lactating sow influences milk production and subsequent reproduction through changes in nutrient intake. The management goal during lactation is to maximize feed intake. Decreasing the effective environmental temperature, increasing the nutrient density of the lactation diet, maintaining fresh adequate supplies of feed and water, and preventing excess weight gain during the prior gestation period will increase nutrient intake during lactation. Effective environmental temperature of the lactating sow can be maintained in the thermoneutral zone by using drip cooling, increased ventilation rates and flooring materials with superior conductive properties. Sow parity, genetics, litter size, and disease level will also influence feed intake. Management practices must account for these factors and, thus, should be tailored to individual farm situations to ensure adequate nutrient intake and prevent aberrations in subsequent reproductive performance. PMID- 1446271 TI - Management of replacement breeding animals. AB - In conclusion, replacement gilts should be finally selected before 110 kg body weight and should have been stimulated to reach puberty by this time. Currently, the best method for achieving this is ad libitum feeding and the correct use of boar exposure. However, whether ad libitum feeding will always be the best feeding strategy remains to be seen. The impressive success of selection programs and the potential for the use of growth promoters and repartitioning agents in the feeder barn may require that future replacements be identified at an early stage and raised under a separate feeding regimen. To produce a large first litter, gilts should be bred at their second estrus. There is unlikely to be any further increase in litter size by delaying mating to third estrus. A major consideration when choosing when to breed replacements is the length of their productive life. For many farms, this may be maximized by delaying breeding until the sow is 120 to 130 kg body weight with a minimum backfat depth of 18 mm. For the producer who is able to exert control over lactation condition loss, however, breeding replacements at about 110 kg body weight with backfat depths of 14 to 16 mm should not adversely affect long-term performance. Although it is true that, under some conditions, the lean gilt may become a problem, it is equally true that her potential is as great as her fatter contemporaries. Whether this potential is realized is largely under the producer's control. Regarding the boar, nutritional management need not vary from that provided for gilts. However, if replacement boars are raised on-farm, it is of great importance that they be allowed to socially interact with other pigs. Failure to provide this opportunity will result in a boar with reduced libido. PMID- 1446272 TI - Nutrition for optimizing breeding herd performance. AB - Modern sows are younger and leaner at time of mating and probably have poorer appetites than sows of 10 to 15 years ago. Therefore, feeding strategies should aim to minimize weight loss and maintain a sow's body condition throughout her reproductive life. The efficiency with which gilts are introduced into the breeding herd is as important in economic terms as is the efficiency with which the sow returns to estrus after weaning. Gilts should be selected at 50 to 60 kg, and fed a 16% protein diet ad libitum until mated at their second estrus, when they weigh 115 to 120 kg and have 17 to 20 mm backfat. Flushing gilts before the onset of second or third estrus increases ovulation rate of restricted gilts to the levels achieved by gilts fed ad libitum. During gestation, maintenance represents 75 to 85% of total energy requirements. The aim should be to achieve 20 to 25 mm backfat at farrowing. Increased feed intake from day 2 to 3 after mating will not increase embryo mortality. Feeding an extra 1 kg feed/sow/day for the last 10 days of gestation increases piglet birth weight slightly and prevents a loss of 1.5 to 2.0 mm of sow backfat. Wherever possible, sows should be fed ad libitum from the day after farrowing until weaning. Reduced feed intake by lactating sows, for whatever reason, results in excessive weight and condition loss. Excessive weight loss in lactation causes extended remating intervals, a lower percentage of sows returning to estrus within 10 days of weaning, reduced pregnancy rate, and reduced embryo survival. Ovulation rate is not affected by level of feed intake in lactation. It has been suggested that sows will have minimum weaning-to-service intervals when they weigh 150 kg or more at weaning. It is likely that the sow must be anabolic for about 10 days before she will exhibit postweaning estrus. The decision when to rebreed is made some time prior to weaning and is mediated by a host of substrates, hormones, and neurotransmitters. Sows with a delayed return to estrus also have a lower pregnancy rate and smaller subsequent litters. If sows lose considerable weight or condition during lactation, a high level of feeding in the postweaning period will improve embryo survival. PMID- 1446273 TI - Optimizing farrowing rate and litter size and minimizing nonproductive sow days. AB - The most universally accepted measure of reproductive performance is PSY. Excellence is achieved by reducing NPD, increasing liveborn litter size, and reducing preweaning mortality. To reduce NPD, farm management should be directed to improve farrowing rate. Matings that occur in late summer usually are less fertile as the result of the pig's normal seasonal variation. Confinement gestation stalls are the best prevention for the reduced farrowing rate caused by season. Liveborn litter size is the result of a mixture of genetic and management variables. F1 females have the highest heterosis. The management variables of age at first mating, wean-to-service interval, skip mating, lactation length, and parity all influence litter size. PMID- 1446274 TI - Stillbirths, mummies, abortions, and early embryonic death. AB - Stillbirths, mummies, abortions, and early embryonic death have a substantial impact on the profitability of a farm in both endemic and epidemic conditions. Fetal death is highly dependent on stage of gestation. Implantation occurs around day 14 postmating in sows, and fetal death of an entire litter at this time usually results in a regular return to service. If more than four embryos remain alive, the sow may go on to farrow normally. If fetal death occurs after implantation but before calcification (around 35 days gestation), the sow will either return to estrus at an irregular interval or will farrow a normal litter of reduced size. Although fetuses are normally resorbed prior to calcification, fetal death after that stage of development leads to mummification. Abortions are more directly related to maternal control of pregnancy than fetal failure. Stillbirths are those pigs that appear normal at birth but have lungs that do not float in water. Causes of fetal death can be divided into infectious and noninfectious categories. Infectious causes perhaps are overemphasized but are certainly important in epidemic situations. Some infectious causes of fetal death are primarily systemic maternal pathogens, whereas others may attack the fetus and/or placenta, directly such as PPV, PEV, PRV, SIRS virus, and Leptospira sp. Several other infectious agents have been associated with fetal death. Noninfectious causes of stillborns, mummies, abortions, and early embryonic death are most common in endemic situations. Most stillbirths are due to difficulty at or around parturition, primarily extended duration causing fetal anoxia. Environmental factors such as increased ambient temperature and seasonal infertility affect death rates, as do specific individual sow characteristics, nutritional factors, and toxicities. The causes of stillborns, mummies, abortions, and early embryonic death are often difficult to ascertain, but the potential rewards make investigation efforts worthwhile. PMID- 1446275 TI - Porcine urogenital disease. AB - Porcine urogenital disease is the result of an imbalance of the normal microflora of the urinary and reproductive tracts brought about by hormonal, environmental, and management-related stress factors. Production and economic losses can be substantial, and diagnosing and treating the problem can be frustrating. Through proper hygiene, facility design, and culling procedures, the severity of the problem can be minimized. PMID- 1446276 TI - Pathogenesis, prevention, and treatment of lactational insufficiency in sows. AB - Lactational insufficiency is one of the major problems in swine production, and the consequences on the growth of the litter must be emphasized. Pathophysiology involves neuroendocrinologic interactions and the role of target organs such as the mammary glands, uterus, bladder, and gut. The complexity of these interactions and the fact that all interactions are not well understood leads to a broad approach. Some risk factors and their associations with lactational insufficiency are described to help the practitioner in the clinical approach to such a problem. PMID- 1446277 TI - Preweaning mortality. AB - A number of factors, both infectious and noninfectious, contribute to preweaning mortality in pigs. It is important to establish the causes of preweaning mortality and their distribution in investigating farm problems. The various causes, risk factors, and a step-by-step approach to solving the problem are discussed. PMID- 1446278 TI - Pharmacologic control of swine reproduction. AB - Current approaches to control fertile estrus and parturition in the pig are discussed. Techniques to induce estrus in acylic pigs (pregnant mare serum gonadotropin and human chorionic gonadotropin) to synchronize estrus in cyclic females (progestins), and to control onset of ovulation (human chorionic gonadotropin) are described. Regimens that induce parturition (prostaglandins) and precipitate farrowings at more predictable times (oxytocin) are addressed. PMID- 1446279 TI - Financial evaluation and decision making in the swine breeding herd. AB - As the swine industry continues to evolve and develop a greater business orientation--one that demands justification of costs, benefits, and risk-exposure -the veterinarian will be confronted with the need to develop an economic basis to supplement the biologic. The profession should view such a challenge as an opportunity to broaden its role in serving the businesses that make up the industry. However, to be effective in such an expanded role requires that the veterinarian develop a good working knowledge of risk and risk management as well as the role played by economic evaluation techniques used in financial evaluation in the risk management process. Several potential advantages exist for the veterinarian who determines to expand his or her risk management role by using financial evaluation in the course of day-to-day practice routine: Additional service or consulting income may be generated through evaluating alternatives through decision analysis. Client confidence may be strengthened in the veterinarian and in the recommendations made. The costs of consulting services and health products for the client may be viewed as income-generators instead of being viewed solely as expenses. Referrals of additional progressive clients may be generated by satisfied current clients. The veterinarian may achieve personal satisfaction through substantiating his or her recommendation beyond clinical or experimental judgment. With the capability of using financial evaluation techniques in the evaluation and justification of recommendations comes significant responsibility. Reliance upon financial evaluation techniques as a more objective approach in the management of risk for clients carries with it an inherently greater degree of trust. Such trust must be deserved. The universal adage "garbage in, garbage out" applies directly to financial evaluation. Financial evaluation techniques have the potential to provide the decision-maker with objective and accurate analysis, improving the probability of choosing an optimal course of action for the business. However, the objectivity and accuracy achievable is highly dependent upon the quality and quantity of information used in the analysis. Veterinarians must be cognizant of the increased responsibility demand placed on those using financial evaluation techniques to direct the course of action for their clients. Financial evaluation tools are available to decision makers that may improve the objectivity of the decision-making process, providing for a greater degree of confidence in the expected outcome. Stated another way, these tools can reduce the number of surprises a decision-maker encounters as a result of the decisions made.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446280 TI - [Uses of vein to substitute tendon sheath in repair of flexor tendon in the "no man region"]. PMID- 1446281 TI - [Le Fort I osteotomy in the correction of maxillary deformity]. PMID- 1446282 TI - [Experiences of mammaplasty in 32 patients of macromastia and mammary descensus]. AB - 32 patients with macromastia and mammary descensus have been treated since 1982 by means of mammoplasty. The Mckissock's operation was modified to make the surgical procedure simple and rational, easy to grasp, safe and reliable. According to our experiences, the advantages of the operation, the complications and their prevention and management have been discussed in the present communication. PMID- 1446283 TI - [Reconstruction of breasts using transverse lower abdomen rectus myocutaneous flap. A report of 5 cases]. PMID- 1446284 TI - [Clinical analysis of fluid resuscitation in severe burned patients with or without inhalation injury]. AB - The amount of fluid resuscitation, estimated according to crystal-colloid for formula, were retrospectively studied in 55 cases of severe burned patients with or without inhalation injury. These cases were divided into two groups. One group consisted of patients with inhalation injury, while the another there was no inhalation injury. The result showed that patients in the former required 13.5% additional amount of fluids over the latter in the first 24 hours postburn, and this amount was mainly due to the additional requirement in the first 8 hour period. We propose that the amount required in severe burned patients with inhalation injury in the first 24 hours postburn should be appropriately increased, and special attention should be paid to the harmful effect of inadequate fluid resuscitation in the first 8 hour period. The amount of fluids required for resuscitation in severe burned patients with inhalation injury, as estimated according to crystal-colloid formula, should be increased by 13.5% in the first 24 hours, and 2/3 of the addition amount should be given in the first 8 hours, with 1/3 of it in the second and third 8 hours postburn. PMID- 1446285 TI - [Repair of hypospadias using 2 newly designed island flaps]. PMID- 1446286 TI - [Repair of flexion contracture of fingers with paired trapezoid skin flaps]. PMID- 1446287 TI - [Transplantation of thin pedicle skin flap: a new method in the treatment of skin defect of hand (a report of 54 cases)]. AB - We used the transplantation of the thin pedicle skin flap to repair the skin defect on the hand and claw hand due to scar contracture in 54 patients. The results were improved. The size of the skin flaps was 16-8 cm x 6-4 cm. The average time of division of the pedicle was 10.5 days. In comparison with the free skin graft with a preserved subcutaneous vascular network, the whole thickness free skin graft, the random pattern skin flap (local flap, fascio cutaneous flap and traditional skin flap), the axial pattern skin flap (including island skin flap and myocutaneous flap), showed that the thin pedicle skin flap was superior over them. The indications, blood circulation and the points for attention in the operation were discussed. PMID- 1446288 TI - [An experimental study of mitogen-stimulated blastogenic transformation and interleukin-2 in mice after burn injury]. AB - In this study, mitogen-stimulated blastogenic transformation (MSBT) and interleukin 2 (IL-2) production by splenic lymphocytes in mice were measured at various time intervals after unanesthetized burn injury. The results showed that both MSBT and IL-2 production were suppressed after burn injury. There was a significant positive correlation between these two parameters. The postburn serum showed in vitro suppressive activity upon MSBT, IL-2 production and IL-2-IL-2R interaction of normal control. The results indicated that burn injury had a significant effect on lymphocytes. PMID- 1446289 TI - [Changes in malondialdehyde contents in serum and tissues after ischemia and reperfusion of the bowel in dogs]. AB - The portal circulation was reduced to 50% for one hour by partially occluding the superior mesenteric artery, and the relationship between the changes in malondialdehyde (MDA) and multiple organ damage was studied. The results showed that there was a marked change in hepatic enzymology, with MDA values significantly elevated in serum and lung and liver tissues after the reperfusion when compared with controls. These results suggested that lipid peroxidation initiated by free oxygen radicals played an important role in the multiple organ damages, and the extent of organ damage was closely correlated with the contents of MDA in tissues. PMID- 1446290 TI - [Uses in fibronectin on eschar-excised wound to promote expansion of skin grafts]. AB - Fibronectin was applied to wounds resulted from excision of burn eschars at different time intervals after burn in piglets, for the purpose of studying the effect of Fn in promoting the expansion of skin grafts which were laid on the wounds. Fn content in wound tissue was measured by means of ELISA, while tissue Fn and Type-III collagen localization was identified by immunohistochemical method ABC. The rate of the graft expansion was then measured by Automated Scanning Image Analyzer. The results showed that topical application of exogenous Fn on the wound could rapidly increase the density gradient of tissue Fn on the wound and promote expansion of skin grafts. PMID- 1446291 TI - [Effect of crystal No 4 of Polygonum cuspidatum on microcirculatory disturbances during burn shock]. AB - A model of burn shock was reproduced in rat. The effects of crystal No 4 of Polygonum cuspidatum (p. c.) on microcirculation of spinotrapezius muscle in rat with burn shock were observed with a special Hitachi TV set with magnification of 4000x. The changes in water content in tissues of lung and burned skin were measured. The survival time of burned animals was recorded. The aggregation of WBC and the degree of tissue damage in lung were examined in pathologic slides. The results showed that during burn shock the number of adhesive WBC in venules was about 8 times more than normal, the amount of open capillaries was reduced by 3/5 of normal. There were apparent aggregation of WBC and tissue damage in the lung. The number of adhesive WBC was decreased by 80%, the amount of open capillary returned to near normal, and the aggregation of WBC and the degree of tissue damage in the lung were alleviated by administration of crystal No 4 of Polygonum cuspidatum. The survival time in p. c.-treated group was prolonged 1.9 fold of that in n.s.-treated group. The results indicated that the decrease of WBC adherence was caused by, on the one hand, the increase of driving force and wall stress after treatment of p.c., and on the other hand, p. c. might affect some humoral factors which promoted WBC adherence. PMID- 1446292 TI - [Acceleration of epidermis proliferation by direct current stimulation (an experimental study)]. AB - An experimental study was designed to evaluate the effect of direct current stimulation on the rate of epidermis proliferation using guinea pigs. In the study, two full thickness skin defects were made over the paravertebral region in each animal. The edges of wounds were transfixed. One of the wounds in each animal received the DC stimulation, and the other did not. The 44 animals were divided into four groups of eleven animals each, the stimulation strengths were 10 muADC, 30 muADC, 50 muADC, 0 muADC respectively. The results showed that the rate of epidermal cell proliferation and wound healing with the DC stimulation were faster, especially on the side of the negative electrode, and the rate of healing of the unstimulated wound in animals which received stimulation in the contralateral wound was faster than that of wounds of control animals. PMID- 1446293 TI - [Plasmid fingerprinting technique analysis of Pseudomonas aeruginosa isolated from a burn unit]. AB - We used plasmid fingerprinting technique to analyse 50 strains of Pseudomonas aeruginosa isolated from our burn unit and 15 strains of Pseudomonas aeruginosa from other wards. The results revealed that the carrier rate of R-plasmid was 100%. All 50 strains of Pseudomonas aeruginosa from burn units contained one plasmid with approximate molecular weight of 55 kb. Among 15 strains of Pseudomonas aeruginosa from other wards, 10 strains contained one plasmid with the same molecular weight. However, 3 strains were found to possess an additional 12.5-kd plasmid and 2 strains contained 77-kb plasmid. This proves that R-plasmid carrying Pseudomonas aeruginosa is prevalent in the burn unit, and R-plasmid is disseminated in the hospital. PMID- 1446294 TI - [Hematopoietic response to thermal injury]. PMID- 1446295 TI - [Study of the abnormal plasma proteins after burn injury]. AB - In our previous study at least 4 abnormal bands were found in burned sera when analyzed by SDS-PAGE. In this paper further exploration of the characteristics of these abnormalities of burned sera were presented. By way of western blotting, 12 kinds of antisera against different human proteins as detecting antibodies were used. Results showed that bands developed by anti-haptoglobin antiserum corresponded well with the abnormal bands in SDS-PAGE. If the burned serum was separated by ion-exchange chromatography and its collected eluates containing protein peaks were tested for the immunosuppressive activities on normal murine spleen lymphocytes, the immunosuppressive eluates were usually found in the 6th protein peak. When these immunosuppressive eluates were further analyzed by SDS PAGE and Western blotting, bands stained with anti-haptoglobin antiserum still coincided with the abnormal bands found in SDS-PAGE of burned serum. Result of this study suggests that one of the immunosuppressive factors found in burned serum may be a haptoglobin-like substance. PMID- 1446296 TI - [Lengthening of residual digit by gradual traction and bone grafting (a report of 143 cases)]. AB - Since 1985, a device for gradual traction was used for lengthening of 143 residual digits in 75 patients. The average lengthening was 2.2 cm. This method is simple, safe, and effective. The advantages of this method over the previously exercised tubed bone graft and other digital lengthening methods are that the digit reconstructed by the gradual traction-lengthening method has the normal cutaneous structure, good sensation function, and better contour. Multiple digits can be reconstructed simultaneously. Because the periosteum at the osteotomy site is kept intact, the long term results are consistent. PMID- 1446297 TI - [Quantitative bacterial culture of subeschar tissue. A clinical study]. AB - The relationship between the number of bacteria in the subeschar tissue and time, age, burn extent in 47 patients within a week after burn injury are presented. The results showed 1. There is a significant positive correlation between the number of bacteria in the subeschar tissue and time intervals following burn within the first week (r = 0.9839, P < 0.01); 2. In children (below 4 years) and patients over 45 years, there is a higher incidence of having bacterial counts of over 10(5)/gm of tissue than that of young and adolescent patients (P < 0.01); 3. There is a significant difference in subeschar bacterial count between major burns (> 30% TBSA) and smaller burns (< 30% TBSA P < 0.05); 4. Pseudomonas aeruginosa is one of the most frequent bacteria isolated, especially in major burns. PMID- 1446298 TI - Jesus Christ--the hope of nursing. Does He make a difference? PMID- 1446300 TI - Meaning in nursing. PMID- 1446299 TI - New horizons. PMID- 1446301 TI - Professional identity. PMID- 1446302 TI - 13C-CP/MAS NMR studies of the cyclomalto-oligosaccharide (cyclodextrin) hydrates. AB - The 13C-CP/MAS NMR spectra of cyclomaltohexaose (alpha-cyclodextrin) hexahydrate, cyclomaltoheptaose (beta-cyclodextrin) "undecahydrate", cyclomalto-octaose (gamma cyclodextrin) "octadecahydrate", and of the same materials at lower levels of hydration are compared with solution NMR data, structures obtained from single crystal diffraction studies, and with previous reports of the 13C-CP/MAS NMR spectra. The chemical shifts of the C-1 and C-4 resonances can be correlated with the conformation about the (1----4) linkage. The chemical shifts of the C-6 resonances are also sensitive to hydrogen-bonding interactions, as shown by the spectral changes on loss of water from the structures. The results suggest that, for resonances of carbon atoms close to a centre of significant conformational change, chemical shifts may be predicted on the basis of conformation alone, but for the resonances of more distant atoms, changes in chemical shift due to conformational change may be masked by the effects of alterations in the local environment. PMID- 1446303 TI - A spacer-modified disaccharide as a photoaffinity reagent for the acceptor binding area of bovine (1----4)-beta-D-galactosyltransferase: comparison of its acceptor properties with those of other 2-acetamido-2-deoxy-beta-D glucopyranosides. AB - The spacer-modified disaccharide 1,10-di-O-(2-acetamido-2-deoxy-beta-D glucopyranosyl)-2-azi-1,10- decanediol (10) that mimics the biantennary core heptasaccharide of N-glycoproteins has been synthesised. Compound 10 is an excellent acceptor in galactosyltransferase-catalysed galactosylation by UDP galactose, is superior (7-8-fold) to analogues that have only one GlcNAc unit, and is an efficient photoaffinity reagent for galactosyltransferase. In the presence of UDP-Gal, no photoaffinity labelling by 10 takes place, which agrees with the mechanism of galactosyltransferase action. PMID- 1446304 TI - Spacer-modified trisaccharide glycosides that mimic the biantennary Asn-linked oligosaccharide acceptor of (1----4)-beta-D-galactosyltransferase and can be used as competitive inhibitors and for irreversible deactivation. AB - The biantennary spacer-modified trisaccharide glycoside methyl 3,6-di-O-(2 acetamido-2-deoxy-beta-D-glucopyranosyloxyethyl)-alpha -D- mannopyranoside (5) was synthesised and used together with several 2-acylamino-2-deoxy-D-glucose derivatives in competition experiments with beta-D-galactosyltransferase. Compound 5 was an acceptor substrate (KM 0.18 mM) comparable to the biantennary core heptasaccharide of glycoproteins (KM 0.13 mM). Replacing the N-acetyl group by other N-acyl groups did not alter the kinetic parameters significantly. When the N-acyl group was iodoacetyl, the compound was an irreversible inhibitor. PMID- 1446305 TI - Conformational analysis of the anomeric forms of sophorose, laminarabiose, and cellobiose using MM3. AB - Relaxed-residue energy maps based on the MM3 force-field were computed for relative orientations of the pyranosyl rings of sophorose, laminarabiose, and cellobiose, respectively the (1----2)-beta-; (1----3)-beta-; and (1----4)-beta linked D-glucosyl disaccharides. Sixteen starting conformations of the rotatable exocyclic side-groups were considered for each molecule. All of the energy surfaces have two intersecting low-energy troughs and illustrate the importance of exo-anomeric effects in determining disaccharide conformation. Local minima were found by relaxed minimization without restriction. The energy surfaces of these disaccharides are very similar to the energy surfaces of their corresponding 6-methyltetrahydropyran analogues. There is good agreement between disaccharide structures having minimal MM3 energy and those found by crystallography. PMID- 1446306 TI - Structural characterization of a novel diglycosyl diacylglyceride glycolipid from Rhizobium trifolii ANU843. AB - A novel glycolipid was isolated by chloroform-methanol extraction of Rhizobium trifolii ANU843 cells. Compositional analysis, methylation studies, 1H NMR and spectroscopies led to the identification of a diglycosyl diacylglyceride: 1,2-di O-acyl-3-O-[alpha-D-glucopyranosyl-(1----3)-O-alpha-D- mannopyranosyl]glycerol. Iso-hexadecanoic and anteiso-heptadecanoic acids were the predominant fatty acids esterifying the glyceryl moiety, but a microheterogeneity in fatty acid composition was found, resulting in at least five distinct molecular species of the glycolipid. Although widespread in plants, animals and Gram-positive bacteria, glycosyl glycerides have been seldom reported in Gram-negative bacteria and this work is the first evidence of their occurrence in the bacterial family Rhizobiaceae. PMID- 1446307 TI - Artificial antigens. Synthetic carbohydrate haptens immobilized on crystalline bacterial surface layer glycoproteins. AB - The crystalline surface-layer glycoproteins of Clostridium thermohydrosulfuricum L111-69, Bacillus stearothermophilus NRS 2004/3a and Bacillus alvei CCM 2051 were used for immobilization of spacer-linked blood group A-trisaccharide (alpha GalNAc(1----3)[alpha Fuc(1----2)]beta Gal) and of the spacer-linked, tumor associated T-disaccharide [beta Gal(1----3)alpha GalNAc]. The immobilization involved the glycan portions of surface-layer glycoproteins. Different activation methods were used, namely, periodate oxidation, or treatment with epichlorohydrin or divinyl sulfone, followed by coupling of the hapten under appropriate conditions. The resulting conjugates are useful for assessing the application potential of haptenated surface layer preparations as carrier/adjuvants for the induction of immunity to poorly immunogenic molecules. PMID- 1446308 TI - Structural elucidation of the capsular polysaccharide of E. coli serotype K47. AB - The capsular polysaccharide from Escherichia coli K47 was investigated using mainly methylation analysis and 1H and 13C NMR spectroscopy and shown to have the following repeating unit: [Formula: see text] PMID- 1446309 TI - Structural variability in the glucuronoxylomannan of Cryptococcus neoformans serotype A isolates determined by 13C NMR spectroscopy. AB - Cryptococcus neoformans, the etiologic agent of cryptococcal meningoencephalitis, produces glucuronoxylomannan (GXM) as the major capsule component. Purified GXMs obtained from eight serotype A isolates of C. neoformans were treated by ultrasonic irradiation and then O-deacetylated prior to their comprehensive chemical analysis by GLC, GLC-MS, and 13C NMR spectroscopy. The average xylose: mannose: glucuronic acid molar ratio of the eight isolates is 1.96 +/- 0.25: 3.00: 0.58 +/- 0.10. Methylation analyses and 13C NMR spectroscopy show a general structure for GXM that is comprised of a linear (1----3)-alpha-D-mannopyranan substituted with beta-D-GlcpA and with beta-D-Xylp at O-2. Variable quantities of unsubstituted (1----3)-alpha-D-Manp were observed between the eight isolates studied. In several isolates some of the (1----3)-alpha-D-Manp residues are disubstituted with beta-D-GlcpA at O-2 and with beta-D-Xylp at O-4; this type of substitution was not previously thought to occur in serotype A isolates. Heterogeneity, between isolates, in the disposition of the substituents along the mannopyranan backbone was revealed by 13C NMR spectroscopy. The eight isolates, and three isolates previously studied, were each assigned to one of four distinct groups based on the 13C NMR chemical shifts of the anomeric carbons. Six of the eleven isolates gave identical spectra (Group I). The six major anomeric resonances from Group I were assigned to specific glycosidic linkages present in GXM. The remaining five isolates gave more complex spectra that are indicative of additional linkages and comprise the remaining three groups. Three of these five isolates contain substantial amounts of linkages previously thought to be distinctive of serotypes B and C, i.e., Manp residues that are 4-O-glycosylated with beta-D-Xylp. Methylation analyses only predicted an average repeating unit, whereas 13C NMR spectroscopy demonstrated that GXM from each isolate may be categorized into four groups by the occurrence of distinct sequences of carbohydrate residues. PMID- 1446310 TI - Negative-ion fast-atom-bombardment mass spectrometry of native gangliosides using a high-polar matrix system. PMID- 1446311 TI - The major capsular polysaccharide of Cryptococcus neoformans serotype B. PMID- 1446312 TI - The application of NMR-pattern-recognition methods to the classification of peracetylated oligosaccharide residues: effects of intraclass structure. PMID- 1446313 TI - Synthesis of disialoganglioside GD1 alpha and its positional isomer. AB - The first total syntheses of disialoganglioside GD1 alpha and its alpha 2-6 positional isomer are described. Suitably protected pentasaccharide derivatives, derived from known pentasaccharide precursors, were selected as the glycosyl acceptors. Using our facile method of stereoselective alpha-glycosidation of sialic acid, these acceptors were coupled with methyl (methyl 5-acetamido-4,7,8,9 tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galact o-2- nonulopyranosid)onate in acetonitrile medium in the presence of dimethyl(methylthio)sulfonium triflate (DMTST) to get the desired di-alpha-sialyl hexasaccharide derivatives in moderate yields. The hexasaccharide trichloroacetimidates upon coupling with (2S,3R,4E)-2 azido-3-O-benzoyl-4-octadecene-1,3-diol gave the corresponding beta-linked sphingosine glycosides in high yields. These were subjected in sequence to selective reduction of the azido group and coupling of the thus formed amino group with octadecanoic acid, O-deacylation, and saponification of the methyl ester groups to obtain ganglioside GD1 alpha and its positional isomer having the main-chain residue 2-6 linked. PMID- 1446314 TI - Effects of drugs on body venous tone, as reflected by mean circulatory filling pressure. AB - The venous system is supremely important in the control of cardiac output. Drugs which affect the venous system have profound effects on haemodynamics. This review comments on the methods available for the determination of venous compliance, resistance, and unstressed volume and describes the mean circulatory filling pressure (MCFP) technique, its usefulness and limitations. The MCFP technique involves the measurement of central venous pressure during brief (5-7 s) circulatory arrest. Mathematically, MCFP is inversely proportional to vascular compliance while experimentally, it is a primary determinant of venous return. The MCFP technique provides a reproducible and relatively non-traumatic means for the estimation of body venous tone in conscious and anaesthetised animals. Drugs examined by this technique include alpha and beta adrenoceptor agonists and antagonists, ganglionic blockers, vasoactive peptides (endothelin, vasopressin, angiotensin, neuropeptide Y), and vasodilators (hydralazine, nitroprusside, glyceryl trinitrate, calcium antagonists, and MCI-154). PMID- 1446315 TI - Role of adenosine receptor activation in myocardial infarct size limitation by ischaemic preconditioning. AB - OBJECTIVE: The aims were to examine the role of adenosine receptors in the mechanism of preconditioning in a chronic rabbit model of myocardial infarction; to assess whether the preconditioning effect is blocked by an adenosine receptor antagonist, 8-phenyltheophylline; and to determine whether an adenosine A1 receptor agonist, R(-)N6-2-phenylisopropyl adenosine (R-PIA), mimics infarct size limitation by preconditioning. METHODS: Myocardial infarction was induced in male rabbits by occlusion of the left coronary artery for 30 min, which was followed by 72 h reperfusion. Before the 30 min ischaemia, rabbits were subjected to one of the following six protocols: (1) untreated control; (2) intravenous injection of 8-phenyltheophylline; (3) preconditioning with 5 min ischaemia; (4) pretreatment with 8-phenyltheophylline plus preconditioning; (5) intravenous injection of R-PIA; or (6) R-PIA plus atrial pacing (240.min-1). Infarct size and area at risk were determined by histology and fluorescent particles, respectively. RESULTS: Preconditioning significantly limited infarct size, normalised as a percent of area at risk (%IS/AR), to 19.2 (SEM 2.3)% v control value of 46.5(2.8)%. 8-Phenyltheophylline alone did not modify the %IS/AR, but its injection before preconditioning attenuated the preconditioning effect such that IS/AR = 34.4(2.5)%. While R-PIA did not achieve statistically significant myocardial salvage, R-PIA plus atrial pacing limited infarct size to 33.7(3.0)% (p<0.05 v control). The R-PIA group had severe hypotension and their infarct sizes were inversely correlated with diastolic blood pressure at reperfusion. There was no such correlation in the R-PIA plus pacing group in which bradycardia and hypotension induced by R-PIA were attenuated by atrial pacing. CONCLUSIONS: The infarct size limiting effect of preconditioning was attenuated by 8 phenyltheophylline, and pretreatment with R-PIA was able to limit myocardial infarct size when severe hypotension was avoided by atrial pacing. These findings suggest that adenosine receptor activation plays a crucial role in the mechanism of preconditioning. PMID- 1446316 TI - Pretreatment with buflomedil enhances ventricular function by reducing the dysfunctional area after transient coronary artery occlusion. AB - OBJECTIVE: The aim was to evaluate whether buflomedil (a drug used to treat peripheral vascular disease and which has a number of pharmacological actions potentially beneficial to dysfunctional myocardium) would preserve myocardial function after transient coronary artery occlusion followed by reperfusion. METHODS: The physiological response to a 15 min balloon occlusion of the left anterior descending coronary artery followed by 1 h of reperfusion was monitored in 17 placebo treated dogs and compared with that of 15 dogs which received 10 mg.kg-1 of buflomedil. Buflomedil or its vehicle were given intravenously. Myocardial blood flow was assessed with radiolabelled microspheres and cardiac function was evaluated with quantitative contrast left ventriculography. RESULTS: Buflomedil did not affect baseline haemodynamic variables or contractile function. At the end of occlusion, there was no difference between dogs receiving vehicle compared with those receiving drug with respect to ejection fraction [33(SD 11)% v 34(11)%] or transmural blood flow [0.23(0.11) v 0.28(0.14) ml.g-1 x min-1]. However, at 30 min after reperfusion, ejection fraction was 89% of normal in the buflomedil group compared with 69% of normal in the placebo group (p < 0.03). This difference was sustained 60 min after reperfusion, and was due in part to slightly enhanced flow during reperfusion and a decrease in the dysfunctional area (16 compared with 28 chords lower than -2 SD from the mean, p < 0.04) in the hearts of dogs receiving buflomedil. Areas at risk were equivalent (15.9% and 15.8% of the left ventricle, respectively). CONCLUSIONS: The results suggest that buflomedil and agents with similar modes of action may be beneficial in preserving ventricular function after transient ischaemia followed by reperfusion. PMID- 1446317 TI - Regional interaction and its effect on patterns of myocardial segmental shortening and lengthening during different models of asynchronous contraction in the dog. AB - OBJECTIVE: The aim was to examine the effect of asynchrony and regional myocardial interaction on the pattern of segmental contraction and relaxation. METHODS: Three models of asynchrony were produced. Firstly the left anterior descending artery was abruptly occluded for 60 s. Secondly, the same artery was gradually occluded to produce four degrees of ischaemia based on the severity of the mechanical dysfunction. Finally, asynchrony was created by infusing isoprenaline (0.04 microgram.ml-1) into the left circumflex artery. Twelve anaesthetised beagles, weighing 16-21 kg, were used for the study. RESULTS: The patterns of contraction and relaxation were characterised by analysing the phases of shortening and lengthening, the peak lengthening rate (dL/dt), and the timing from the onset of systole to minimum systolic length. A consistent pattern of shortening and lengthening was evident during all three models of asynchrony. There were reciprocal relations between the extent of isovolumetric shortening in the normal segment and in the abnormal segment, and on occasion between the extent of isovolumetric shortening in the normal segment and the extent of isovolumetric lengthening in the same segment. Normal segments that showed minimal shortening or even some lengthening during isovolumetric systole tended to shorten beyond ejection, while segments that shortened significantly during isovolumetric contraction, lengthened earlier. Despite no change in isovolumetric shortening, segments also shortened after ejection when the opposite segment lengthened in late systole and early diastole. CONCLUSIONS: The pattern of shortening and lengthening depends on the path of contraction or on its entire loading pattern throughout systole. It is also possible that during early isovolumetric systole a segment can either be unloaded or preloaded by an opposing segment. PMID- 1446318 TI - Antiarrhythmic effects of preconditioning in anaesthetised dogs and rats. AB - OBJECTIVE: The aim was to determine the relationship of the duration of short coronary artery occlusions and of the reperfusion period to the extent of the antiarrhythmic effect of preconditioning. METHODS: A prolonged occlusion of a coronary artery in 102 anaesthetised rats and 55 anaesthetised dogs was preceded by a variable number of preconditioning coronary artery occlusions, of varying duration and with variable reperfusion periods between them and the prolonged occlusion. RESULTS: Preconditioning in both species reduced the severity of ischaemia induced arrhythmias, epicardial ST segment changes, and alterations in the degree of inhomogeneity of conduction during a subsequent prolonged coronary artery occlusion, provided that the reperfusion time was less than 30 min (in rats) and 1 h (in dogs). This antiarrhythmic effect of preconditioning was marked; eg, in dogs following two preconditioning occlusions survival from a combined ischaemia-reperfusion insult was 40% (cf, 0% in the controls). CONCLUSIONS: Short preconditioning periods of myocardial ischaemia protect the myocardium against the arrhythmogenic effects of a more prolonged occlusion. The optimum time for this preconditioning occlusion in rats is 3 min and protection is still apparent 30 min later. In dogs, the protective effect is especially clear with two short (5 min) coronary artery occlusions. The protection in this species lasts for less than 1 h. PMID- 1446319 TI - Effect of adrenaline on cardiac force-interval relationship. AB - OBJECTIVE: The aim was to test the hypothesis that adrenaline affects the force interval processes. METHODS: The force-interval processes were studied in eight guinea pig papillary muscles (isometric force) and five anaesthetised dogs with atrioventricular block (maximum rate of rise of left ventricular pressure, LVdP/dtmax). The contractility indices were measured during pacing sequences in which a steady state was interrupted after a variable interval by a premature beat followed by an immediate return to the steady state. RESULTS: The relationship between contractility of the premature beat and the preceding interstimulus interval displays an approximately monoexponential initial rising phase, ie, mechanical restitution. With increasing adrenaline dosage in the isolated preparation there was always a significant increase in the force, and in its rate of rise with interval in some cases. Adrenaline had a variable accelerating effect on the time course of this mechanical restitution in isolated papillary muscles, but no effect in the dog preparation. In the isolated preparation adrenaline also slowed the decay in potentiation of the two beats immediately following the premature contraction. A slope of the relationship between the contractility of the second potentiated beat and that of the first was thus increased. This difference was not apparent in the intact preparation. CONCLUSIONS: The speeding up of mechanical restitution by adrenaline may be interpreted as reflecting the time course of reavailability of contractile activator. The slope of the relationship of contractility to that of the previous beat during the decay of postextrasystolic potentiation may be interpreted as the recirculation fraction of contractile activator; this is increased by adrenaline. However, in addition, adrenaline exerts an inotropic effect by another mechanism. PMID- 1446320 TI - Evaluation of reperfusion strategy for the globally ischaemic rat heart. Recovery of function and energy metabolism. AB - OBJECTIVE: The sequelae of myocardial ischaemia can in principle be alleviated by repeated reperfusion, but the accumulation of adenosine monophosphate (AMP) and the loss of interstitial adenosine may lead to adenylate depletion. Repeated oxidative stress could predispose the heart to reperfusion injury. The aim of this study was to investigate the effect of intermittent reperfusion on myocardial energetics and postischaemic function. METHODS: Isolated retrogradely perfused rat hearts were subjected to 20 min ischaemia, this being continuous in group I while the hearts in group II were reperfused for three 2 min periods at 5 min intervals. Function and energy metabolism were evaluated during the postischaemic reperfusion. RESULTS: Considerable efflux of adenosine compounds was seen during the final reperfusion, this being greater in group I than in group II, at 6.6(SEM 0.9) v 2.0(0.4) mumol.g-1 dry weight (p < 0.01). Tissue AMP, inorganic phosphate, and adenosine catabolites were higher in group I than in II after the ischaemic insult (p < 0.02), and ATP was higher in group II at the end of the final reperfusion (p < 0.05). All the hearts recovered; however, in group I the rate-pressure product was lower than in group II. CONCLUSIONS: Repetitive reperfusion, although short in duration, is beneficial in ischaemia in terms of lower adenylate loss and better postischaemic recovery. This should be taken into consideration when designing clinical reperfusion interventions. PMID- 1446321 TI - Role of nitric oxide synthesis in the regulation of coronary vascular tone in the isolated perfused rabbit heart. AB - OBJECTIVE: The aim was to study the effects on coronary vascular tone of three inhibitors of nitric oxide (NO) synthesis. METHODS: Studies were performed on isolated perfused hearts of 74 male New Zealand White rabbits fed normal laboratory diet. Resting coronary perfusion pressure was increased to 40-60 mm Hg with the thromboxane mimetic 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F2 alpha (U46619). The effects of NG-monomethyl-L-arginine (L NMMA), N-iminoethyl-L-ornithine (L-NIO), and NG-nitro-L-arginine methyl ester (L NAME) (0.3-300 microM) on resting coronary perfusion pressure were determined. The effects of these compounds, at concentrations that increased the resting perfusion pressure to a similar extent, on the fall in perfusion pressure induced by acetylcholine (0.1 microM) and glyceryl trinitrate (1 microM) were also investigated. In these studies the resting perfusion pressure was maintained at 40-60 mm Hg by reducing the concentration of U46619. RESULTS: L-NMMA, L-NIO, and L-NAME induced concentration dependent increases in resting coronary perfusion pressure (n = 3-9, p < 0.05). L-NAME had the greatest potency and efficacy, increasing the resting pressure by 48.0(SEM 9.6) mm Hg at 30 microM. L-NIO and L NMMA increased perfusion pressure by 27.3(3.0) and 19.5(5.8) mm Hg respectively at the maximum concentration studied (300 microM). However, at concentrations that were equieffective on resting perfusion pressure (15 mm Hg increase), L-NMMA (100 microM), but not L-NIO (25 microM) or L-NAME (4 microM), significantly inhibited the fall in pressure induced by acetylcholine by 57.2(5.0)%, n = 6, p < 0.05. This effect of L-NMMA++ was attributed to a shorter duration of fall and was reversed by L-arginine (300 microM). L-NMMA (100 microM) and L-NIO (25 microM) potentiated the effect of glyceryl trinitrate by increasing the peak fall in perfusion pressure by 75.6(11.0)% and 68.8(24.1)% respectively (n = 6 for each, p < 0.05). CONCLUSIONS: The differential effects of the three inhibitors on resting coronary perfusion pressure and the acetylcholine induced fall in coronary perfusion pressure suggest that basal and stimulated NO synthesis may be differentially regulated. Reduction in the synthesis of endogenous NO by these compounds potentiates the glyceryl trinitrate induced fall in perfusion pressure, which may have important clinical implications. PMID- 1446322 TI - Activation of bovine endothelial thromboxane receptors triggers release of prostacyclin but not EDRF. AB - OBJECTIVE: The aim was to examine the capacity of U46619 (a stable thromboxane A2 mimetic) to mediate release of endothelium derived relaxing factor (EDRF) from bovine aortic endothelial cells, and compare the response to the U46619 dependent release of prostacyclin (PGI2). METHODS: Bovine aortic endothelial cells (AG4762) were cultured in vitro on microcarrier beads, which were then loaded onto a column and perfused. The cells were challenged with U46619, bradykinin, or the Ca2+ ionophore ionomycin in the perfusate, and measurements made of the release of 6-oxo-PGF1 alpha (the stable hydrolysis product of PGI2, measured by radioimmunoassay) and EDRF (bioassay). Cells were also cultured on glass cover slips, loaded with Fura 2-AM, and measurements made of the rise in intracellular Ca2+ after challenge with U46619, bradykinin or ionomycin. RESULTS: U46619 triggered release of 6-oxo-PGF1 alpha but not EDRF from AG4762 cells, contrasting with bradykinin which released both 6-oxo-PGF1 alpha and EDRF. Ionomycin had little or no capacity to mimic and trigger release of 6-oxo-PGF1 alpha, although ionomycin mediated large increases in intracellular Ca2+. In contrast, staurosporine (a putative inhibitor of protein kinase C) substantially inhibited the U46619 and bradykinin dependent release of 6-oxo-PGF1 alpha. CONCLUSIONS: In contrast to bradykinin linked receptors on AG4762 endothelial cells, which are coupled to the release of both prostacyclin and EDRF, activation of thromboxane A2 receptors on these cells selectively triggers release of PGI2 but not EDRF. Further, based on the distinct effects of ionomycin and staurosporine, it appears that agonist stimulated PGI2 release from these cells is mediated predominantly by protein kinase C, rather than by rises in intracellular Ca2+. This observation contrasts with previously described mechanisms of PGI2 release from endothelium obtained from other sources. PMID- 1446323 TI - Hypoxic preconditioning of ischaemic canine myocardium. AB - OBJECTIVE: The aim was to test whether a brief period of non-ischaemic hypoxia can precondition myocardium. METHODS: 60 anaesthetised adult mongrel dogs of either sex underwent 60 min occlusion of the left anterior descending coronary artery, followed by 5 h reperfusion. In treated groups, hearts were either preconditioned with 5 min coronary perfusion with hypoxic blood [O2 content 9.2(SEM 0.6) ml.litre-1] or 5 min occlusion followed by a 10 min reperfusion period prior to 60 min occlusion. The effect of these treatments on myocardial infarct size and regional contractile function was assessed. RESULTS: Infarct size, determined by tetrazolium staining, as a percentage of anatomical area at risk was markedly decreased in hypoxia preconditioned hearts, at 7.2(1.8)% v 22.4(4.6)% in controls (p < 0.01), but did not differ from ischaemia preconditioned hearts [4.6(1.7)%; p < 0.01 v control]. Anatomical area at risk, expressed as a percentage of left ventricular mass, and collateral blood flow to the inner two thirds of the ischaemic wall did not differ among the groups. Regional contractile function was depressed following ischaemic preconditioning but not following hypoxic preconditioning. During reperfusion following 60 min occlusion, marked paradoxical systolic lengthening was evident in ischaemia preconditioned and control hearts but not in hypoxia preconditioned myocardium. CONCLUSIONS: Five minutes of hypoxic and ischaemic preconditioning were equipotent in preventing infarction, whereas ischaemic preconditioning caused a greater decrement in postischaemic contractile function. PMID- 1446325 TI - Nitric oxide and regulation of coronary vascular tone. PMID- 1446324 TI - Cardiac A2 adenosine receptors--influence of ischaemia. AB - OBJECTIVE: The aim was to detect cardiac A2 adenosine receptors through radioligand binding, and to assess the effect of ischaemia on these receptors. METHODS: Isolated working rat hearts were subjected either to aerobic perfusion or to global ischaemia. A membrane fraction was prepared from ventricular tissue, and 3H-5'-N-ethylcarboxamide adenosine (NECA) binding was determined in the presence of N6-cyclopentyl adenosine (CPA). A2 binding was calculated as the fraction of NECA binding displaced by 100 microM CPA but not displaced by 50 nM CPA. RESULTS: Analysis of A2 NECA binding according to single binding site model yielded Kd = 22.0 nM, Bmax = 34.0 fmol.mg-1 in control hearts; Kd = 49.7 nM, Bmax = 44.3 fmol.mg-1 in hearts subjected to 30 min ischaemia (p < 0.05 for difference in Kd). In the control group a two site model provided a significantly (p < 0.05) better fit (Kd = 5.6 and 183.7 nM, Bmax = 9.5 and 64.4 fmol.mg-1 for the high and low affinity sites respectively). The high affinity component of A2 NECA binding disappeared in the presence of the GTP analogue guanyl-5'-yl imidodiphosphate, suggesting the existence of multiple coupling states of the receptor. In the ischaemic group no significant improvement in data fitting was obtained with the two site model. CONCLUSIONS: The results provide evidence of the existence of cardiac A2 adenosine receptors. Ischaemia modifies receptor properties and appears to affect chiefly the high affinity component of A2 binding, possibly by preventing receptor interaction with membrane G proteins. PMID- 1446326 TI - Hypoxic preconditioning of ischaemic myocardium. PMID- 1446327 TI - Nitric oxide and endotoxin shock. PMID- 1446328 TI - Coronary aneurysms: a case report and review. AB - This case report describes a large coronary aneurysm and poses questions regarding management. The discussion that follows addresses what is known about the natural history of and options for management of coronary aneurysms. PMID- 1446329 TI - Left main coronary artery aneurysm following percutaneous transluminal angioplasty: a report of a case and review of the literature. AB - Since its introduction in 1977, the number of PTCAs and its indications have grown. Along with more frequent usage, newer complications have been reported. Aneurysm of left main coronary artery is rare. This report describes the formation of a new non-obstructing aneurysm in the left main coronary artery after PTCA of left circumflex artery. The patient has had 7 yr of follow-up with a benign clinical course. PMID- 1446330 TI - Coronary artery aneurysm formation following directional coronary atherectomy. AB - Directional coronary atherectomy has recently become available to treat coronary stenosis by excision and removal of tissue. The optimal depth of resection by this method has not been determined and complications have occurred. This report describes the formation of a coronary aneurysm at an atherectomy site in an asymptomatic patient, a finding not reported previously. PMID- 1446331 TI - Case report: formation of vessel aneurysm after stand alone coronary excimer laser angioplasty. AB - Formation of aneurysms in coronary arteries can be observed following percutaneous transluminal balloon angioplasty but has not been reported previously after coronary excimer laser angioplasty in humans. Stand alone coronary excimer laser angioplasty was performed in a 49-year-old man with a 75% left anterior descending artery stenotic lesion and exertional angina, documenting a good angiographic result postintervention. Control angiography 6 months after the procedure revealed an aneurysm distal to a 90% restenosis in the area of ablation. PMID- 1446332 TI - Aneurysmal formation after successful pulsed laser coronary angioplasty. AB - We report two cases of coronary artery aneurysmal formation as long term consequences of Ho:YAG and excimer laser coronary angioplasty. This case report suggests that pulsed laser angioplasty may result in severe vessel wall damage that may lead ultimately to aneurysmal formation. PMID- 1446333 TI - An unusual cause of recurrent angina two years after coronary artery bypass grafting: fistula between internal mammary artery graft to pulmonary vasculature. AB - A 55-year-old man developed recurrent angina pectoris 2 years after coronary artery bypass grafting. Cardiac catheterization demonstrated that the venous grafts were patent, but selective left internal mammary angiogram showed multiple fistulous connections between the internal mammary artery and the pulmonary vasculature of the left upper lobe. After surgical correction of the fistula, the angina resolved. Only three previous cases of acquired internal mammary artery graft fistulas draining to the pulmonary vasculature have been described. The etiology, clinical presentation, and management of an internal mammary artery fistula to the pulmonary vasculature are discussed. PMID- 1446334 TI - Balloon dilation of the completely occluded Blalock-Taussig anastomosis: a case report. PMID- 1446335 TI - Angioplasty of tortuous left internal mammary artery: description of a new technique. AB - Angioplasty of the distal anastomosis site of a markedly tortuous left internal mammary artery (LIMA)--anterior descending artery is described. Tortuosity of LIMA was negotiated using the Tracker-Seeker catheter guidewire system. Angioplasty was then performed using the conventional technique. PMID- 1446336 TI - Detachable balloon embolization of an iatrogenic aortocoronary arteriovenous fistula combined with aortocoronary bypass PTCA: a case report. AB - Coronary artery bypass surgery was performed in a 54-year-old male, and one of the grafts was inadvertently sutured to the vena cordis magna instead of to the left anterior descending coronary artery (LAD). Four years later the patient observed a progression of symptoms including episodes of angina pectoris at rest. Coronary angiography showed stenosis of one of the bypass grafts and notable dilatation of an iatrogenic arteriovenous (A-V) fistula. The stenosed bypass graft was dilated and the A-V fistula occluded by use of a detachable balloon. Embolization was performed rather than surgery, as the LAD was found to be a poor surgical target. The patient's symptoms improved after the procedure; he was followed for 18 months during which time his condition remained stable. PMID- 1446337 TI - Combined PTCA and microcoil embolization of a left internal mammary artery graft. AB - Internal mammary arteries are increasingly common conduits for coronary revascularization. Although infrequent, cardiologists are faced with a number of technical failures. We describe a case of combined PTCA to a LIMA insertion stenosis, along with coil embolization of a large unligated intercostal side branch. A complication of embolization is described along with angiographic follow-up. PMID- 1446338 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: pressure wave artifacts. PMID- 1446339 TI - Modified "kissing" atherectomy procedure with dependable protection of side branches by two-wire technique. AB - We report a new two-wire atherectomy technique for side branch protection. Newer, more resilient wire designs are capable of withstanding cutting forces of the Simpson atherocath device. This technique expands atherectomy application to lesions previously excluded from atherectomy as high risk lesions. PMID- 1446340 TI - Mobile catheterization laboratories. PMID- 1446341 TI - Clinical results and quality of life after percutaneous transluminal coronary angioplasty: a preliminary report. AB - To evaluate the effect of percutaneous transluminal coronary angioplasty (PTCA) on quality of life, data on symptomatic status, functional capacity, life satisfaction, and psychological wellness were collected on 102 patients at 1 day pre-PTCA and 2 months post-PTCA, and on the first 50 of these patients at 10 months post-PTCA. There were highly significant changes (p < 0.001) in all quality of life measures between pre-PTCA and the 1st follow-up measurements. No further significant changes occurred in these measures between the 1st and 2nd follow-up measurements, indicating that the initial improvement in quality of life was sustained over this period. Data on primary success rate, complications, and pre- and post-PTCA risk factor scores are also reported. PMID- 1446342 TI - Improved quality of life after PTCA: generalizability and concerns. PMID- 1446344 TI - The cell nucleus, the unexplored organelle. PMID- 1446343 TI - Does the AHA/ACC task force grading system predict outcome in multivessel coronary angioplasty? AB - To assess the ACC/AHA task force grading system as a predictor of outcome in patients undergoing multivessel percutaneous transluminal coronary angioplasty we analyzed all failures (residual stenosis > 50%, Q-wave myocardial infarction, coronary artery bypass grafting during hospitalization, or death) in 97 patients with 328 stenoses. There were 70 males and 27 females; 60 patients had stable angina, and 37 had unstable angina. The mean number of lesions dilated per patient was 3.4 (range 2-8). The mean preangioplasty percent luminal diameter narrowing was 80 +/- 14%. Thirty-eight stenoses were AHA/ACC classification type A, 192 type B, and 98 type C. One hundred twenty-eight lesions were located in the left anterior descending artery or its distribution, 89 in the left circumflex, 96 in the right coronary artery, and 15 in other vessels. Procedural success (< 50% residual diameter narrowing and no major ischemic complications) was achieved in 266 lesions (81.1%). Major ischemic complications (death, myocardial infarction, or emergency bypass surgery) occurred in 8 patients (8.2%) and in-hospital mortality was 2%. Analysis on a per stenosis basis demonstrated 84% success in type A, 89% in type B, and 64% in type C (p < 0.0001). When type B was divided into type B1 (1 type B characteristic) and type B2 (two or more type B characteristics) the success rate was 90% vs. 88% and the complication rate was 1% vs. 2%, respectively (p = n.s.). Logistic regression analysis showed that the best single predictor of failed angioplasty was total occlusion > 3 months, followed by total occlusion < 3 months and severely angulated (> 90 degrees) segment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446345 TI - Special issue: The cell nucleus, the unexplored organelle. PMID- 1446346 TI - The attachments of chromatin loops to the nucleoskeleton. AB - It is widely assumed by cell biologists that chromatin is looped by attachment to some nuclear skeleton. 'Structural' attachments might be mediated through specific sequences; these would be attached in most cells in an organism, underlying the basic structure of the mitotic chromosome and persisting throughout interphase. 'Functional' attachments might also exist, perhaps if active polymerases are attached to the skeleton and replication and transcription occur as DNA is reeled through them. Cells of different tissues--and even cells of the same tissue--would have different attachments of this type. Problems associated with demonstrating these two kinds of attachment are discussed. We find little good evidence for 'structural' attachments and explore the idea that 'functional' attachments are the only kind that exist: 'functional' attachments involving active transcription units might be stable enough to organize chromatin during both interphase and mitosis, but 'dynamic' enough to allow duplication of attached sequences without disrupting loops. PMID- 1446347 TI - The transcribed template and the transcription loop in Balbiani rings. AB - The active Balbiani ring (BR) genes in the giant puffs in Chironomus salivary glands can be visualized in three dimensions within the cell nucleus. The chromatin template exhibits a dynamic structure: at the RNA polymerases the template is fully extended, while in between polymerases it can be packed into a nucleosome, a nucleosome filament, or even into a thick chromatin fiber, if the spacing between consecutive polymerases is large enough. Even in its extended state, the template harbours histone H1, and most likely also the core histones, indicating that the nucleosomes unfold and refold during transcription. Apart from the transcribed template, a transcription loop contains a thin, extended, apparently flexible and nucleosome-free fiber upstream of the gene, and a loosely coiled nucleosome filament downstream of the gene. PMID- 1446348 TI - DNA replication: the search for support. PMID- 1446349 TI - Synaptosomal complexes and the organization of chromatin during meiotic prophase. PMID- 1446350 TI - Intranuclear sorting and assembly of proteins. PMID- 1446351 TI - Localization of nuclear matrix core filament proteins at interphase and mitosis. AB - The gentle removal of chromatin uncovers a nuclear matrix consisting of two parts: a nuclear lamina connected to the intermediate filaments of the cytoskeleton and an internal matrix of thick, polymorphic fibers connecting the lamina to masses in the nuclear interior. This internal nuclear matrix can be further fractionated to uncover a highly branched network of 9 nm and 13 nm core filaments retaining some enmeshed bodies. The core filament network retains most of the nuclear RNA, as well as the fA12RNP antigen, and may be the most basic or core element of internal nuclear structure. One high molecular weight protein component of the core filament network, the H1B2 antigen, is normally masked in the interphase nucleus and is uncovered as the chromatin condenses at mitosis. This protein is associated with a fibrogranular network surrounding and connected to the chromosomes. The core filament-associated fA12 antigen also becomes associated with this perichromosomal network. We propose that the core filament nuclear matrix structure may not completely disassemble at mitosis but, rather, that parts remain as a structural network connected to chromosomes and other mitotic structures. These mitotic networks may, in turn, serve as the core structures on which the nuclear matrices of daughter cells are built. PMID- 1446352 TI - Three-dimensional immunogold labeling of nuclear matrix proteins in permeabilized cells. AB - A preembedment labeling procedure is described for the three-dimensional (3D) labeling of nuclear matrix proteins in permeabilized cells. The procedure is based on the use of ultra-small (1 nm) gold particles as a marker system. This marker penetrates the nucleus more efficiently than the conventionally used 5-10 nm colloidal gold probes. Dehydration is performed by freeze-substitution to preserve the ultrastructure of the cell as optimally as possible. During freeze substitution the samples are stained by uranyl ions to stain the cellular material throughout the resin section. The 3D gold-labeled and uranyl-stained specimen is embedded in Epon resin and semi-thin (0.2-0.5 microns) sections are made for stereo electron microscopy. The applicability of this method is illustrated by the localization of nuclear matrix-associated nuclear bodies in permeabilized interphase and mitotic HeLa cells. PMID- 1446353 TI - Nuclear frameworks: concepts and operational definitions. PMID- 1446354 TI - Indonesia medicinal plants. III. On the constituents of the bark of Fagara rhetza (Rutaceae). (1): Alkaloids, phenylpropanoids, and acid amide. AB - Two new phenylpropanoids, named O-geranylsinapyl alcohol (1) and O geranylconiferyl alcohol (2), and a new acid amide, named hazeleamide (3), were isolated from the bark of Fagara rhetza (Rutaceae), an Indonesian medicinal plant from Flores Island, Indonesia. The chemical structures of 1, 2, and 3 have been elucidated on the basis of their chemical and physicochemical properties. Among the three new compounds, hazeleamide (3) was found to show a pungent taste and to exert a moderate antimalarial activity in an in vitro test system. PMID- 1446355 TI - Studies on the chemical modification of monensin. IV. Synthesis, sodium ion permeability, and biological activity of 7-O-acyl- and 7-O-alkylmonensins. AB - 7-O-Acyl-(4a-e) and 7-O-alkylmonensins (5a-d) were prepared from monensin (1). Their lipophilicity, sodium ion permeability in human erythrocytes, antibacterial activity and effect on rat tail artery were examined. There was a correlation between lipophilicity and sodium ion permeability as well as between lipophilicity and antibacterial activity. We also found that the compound having larger sodium ion permeability, showed stronger contraction of rat tail artery. 7 O-Benzylmonensin (5c) exhibited higher lipophilicity and larger sodium ion permeability than monensin (1) among the tested monensin derivatives. In addition, antibacterial activity and contractile effect on rat tail artery of 5c were comparable to those of 1. PMID- 1446356 TI - Synthesis of 1,4-dihydropyridine-5-phosphonates and their calcium-antagonistic and antihypertensive activities: novel calcium-antagonist 2 [benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl) 1,4-dihydro-2,6-dim ethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol (NZ-105) and its crystal structure. AB - The effect of the 3-carboxylic-ester variation in 2,2-dimethyltrimethylene 3 alkoxycarbonyl-4-aryl-1,4-dihydro-2,6-dimethyl-5-pyridinephosphonat es (1) was investigated with relation to the calcium-antagonistic and antihypertensive activities: the analogs containing the alkyl groups of not more than 12 carbons and an amino functionality in the carboxylic-ester moiety were synthesized to be examined for biological activities. Among them, 2-[benzyl(phenyl)amino]-ethyl 5 (5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2, 6-dimethyl-4-(3 nitrophenyl)-3-pyridine-carboxylate hydrochloride ethanol (NZ-105) showed particularly beneficial activities and was selected for further pharmacological studies and clinical development. Some aspects of the structure-activity relationships and solid-state structure of NZ-105 by X-ray crystallographic analysis were described. PMID- 1446357 TI - Synthesis and biological activities of optical isomers of 2-(4-diphenylmethyl-1 piperazinyl)ethyl 5-(4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro 2,6-dim ethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate dihydrochloride (NIP-101). AB - Six optical isomers of 2-(4-diphenylmethyl-1-piperazinyl)ethyl 5-(4,6-dimethyl-2 oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3 pyridinecarboxylate dihydrochloride (NIP-101, 1.2HCl.2H2O), a potent calcium antagonist, were successfully prepared by using optically active (2R,4R)-(-)- and (2S,4S)-(+)-2,4-pentanediols, and cis-2,4-pentanediol and optically active (S) (+)-2-methoxy-2-phenylethanol. Their proton nuclear magnetic resonance investigations demonstrate that the 1,3,2-dioxaphosphorinane group is conformationally constrained around the C-P bond. Calcium-antagonistic and hypotensive activities of the optical isomers were examined and found to depend mainly on the absolute configuration at a stereogenic center in the 1,4 dihydropyridine ring rather than the configuration of the 1,3,2 dioxaphosphorinane moiety. PMID- 1446358 TI - Synthesis and crystal structure of optically active 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dim ethyl-4 (3-nitrophenyl)-3-pyridinecarboxylate (NZ-105). AB - (S)-2-[Benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2 yl)-1,4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate ((S)-NZ 105) and R isomer were synthesized through the fractional crystallization of (S) 2-Methoxy-2-phenylethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4 dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate. Calcium antagonism activity was found to reside in the S isomer from single crystal X-ray diffraction analysis. PMID- 1446359 TI - Preparation and pharmacological evaluation of 4-(1,4-benzoquinon-2-yl)-4 phenylbutanamides as potential cerebral protective agents. AB - A new series of 4-(1,4-benzoquinon-2-yl)-4-phenylbutanamides (2) were synthesized for evaluation of their pharmacological activities. All these compounds synthesized showed significant antilipidperoxidation (ALP) activities with brain homogenate in rats and some of them possessed a protective effect against hypobaric hypoxia in mice. Especially, a thiomorpholine derivative (2l, SUN-4757) showed a wide efficacy spectrum to a variety of experimental screening assays designed for cerebral protective agents, and it had a high LD50 value. PMID- 1446360 TI - Novel disease-modifying antirheumatic drugs. I. Synthesis and antiarthritic activity of 2-(4-methylphenyl)benzothiazoles. AB - A series of 2-(4-methylphenyl)benzothiazoles was synthesized and evaluated using an adjuvant-induced arthritic rat model. This class of desired compounds affecting the immune response was found using hemagglutination assay. 4-Acetoxy-2 (4-methylphenyl)benzothiazole (7m), KB-2683, was most potent in the adjuvant induced arthritic rat model and selected for further evaluation. In contrast to nonsteroidal antiinflammatory drugs, compound 7m showed no antiinflammatory or analgesic activities. It did, however, show an immunomodulatory activity in enhanced delayed type hypersensitivity. PMID- 1446361 TI - Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3 triazolo[4,5-d]pyrimidin-9(3H)-one derivatives. II. 6-Alkyl- and 6 cycloalkylalkyl derivatives. AB - A series of 6-alkyl- or 6-(cycloalkylalkyl)-[1,3,4]thiadiazolo[3,2- a]-1,2,3 triazolo[4,5-d]pyrimidin-9(3H)-ones 1b--o was synthesized from the corresponding 1,3,4-thiadiazol-5-amines 3b--o and the antiallergic activities of the products were evaluated. Among the compounds 6-(2-cyclohexylethyl)- [1,3,4]thiadiazolo[3,2 a]-1,2,3-triazolo[4,5-d]pyrimidin-9(3H)-one 1h, whose X-ray crystallographic stereostructure is shown, was found to be a promising new antiallergic agent, which has low toxicity and dual activity as a leukotriene D4 receptor antagonist and as an orally active mast cell stabilizer. PMID- 1446362 TI - Studies on antiinflammatory agents. I. Synthesis and pharmacological properties of 2'-phenoxymethanesulfonanilide derivatives. AB - Various 2'-phenoxymethanesulfonanilide derivatives were synthesized and evaluated for antiinflammatory and analgesic activities. Some compounds bearing an electron attracting substituent at the 4'-position strongly inhibited adjuvant-induced arthritis in rats and acetic acid-induced writhing syndrome in mice without causing gastro-intestinal irritation. Among them, 4'-cyano-(FK867) and 4'-acetyl (FK3311) 2'-(2,4-difluorophenoxy)methanesulfonanilides were selected as the candidates for further development. PMID- 1446363 TI - Synthesis and antibacterial activity of 1-substituted-methyl carbapenems. AB - The synthesis of the 1 alpha- and the 1 beta-substituted (fluoro, cyano, hydroxy and acetoxy)-methyl carbapenems having a 2-(1,3,4-thiadiazol-2-yl)thiomethyl side chain are described, and their in vitro antibacterial activities are compared with the corresponding 1 beta-methyl carbapenems together with imipenem. The synthesis and antibacterial activity of the 1 beta-substituted (fluoro and cyano) methyl carbapenems having 2-(1-alkyl-4-pyridinio)thiomethyl side chains are also described. PMID- 1446364 TI - Syntheses and anti-inflammatory activity of novel oximes and O-acyloximes. AB - Novel oximes were prepared from the corresponding aldehyde or ketone in the usual way, and a number of oxime esters, O-lauroyl, O-2-pyridinecarbonyl, O-nicotinoyl, and O-isonicotinoyl oximes were synthesized by 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide (EDCI)-4-dimethylaminopyridine (DMAP) method or a mixed anhydride method, in our search for potent anti-inflammatory compounds. The anti-inflammatory activity of these compounds was assessed by the carrageenan induced paw edema assay in rats. The oximes (4, 5, and 13), O-lauroyloxime 1L, O nicotinoyloximes (1N, 2N, 3N, and 4N), O-isonicotinoyloxime 1I, and O-2 pyridinecarbonyloxime 7P showed higher anti-inflammatory potency than aspirin, a prostaglandin cyclooxygenase inhibitor. PMID- 1446365 TI - Studies on cerebral protective agents. II. Novel 4-arylpyrimidine derivatives with anti-anoxic and anti-lipid peroxidation activities. (2). AB - In a search for new cerebral protective agents with anti-anoxic (AA) and anti lipid peroxidation (ALP) activities, a series of 4-arylpyrimidines, bearing an amino moiety in the C-5 position of the pyrimidine nucleus, was synthesized and tested for AA and ALP activities. Among them, 6-methyl-5-(4-methylpiperazin-1 ylcarbonyl)-4-(3-nitrophenyl )-2-phenylpyrimidin e (41, FK360) was most effective on both assays and on arachidonate-induced cerebral edema in rats. Structure activity relationships in regard to AA activity of this series of compounds are also discussed. PMID- 1446366 TI - Synthesis and antiarrhythmic activity of 2,5-disubstituted 2,3-dihydro-1,2,5 benzothiadiazepin-4(5H)-one 1,1-dioxides. AB - A series of 2,5-disubstituted 2,3-dihydro-1,2,5-benzothiadiazepin-4(5H)-one 1,1 dioxide derivatives were prepared and evaluated for the antiarrhythmic effect on ouabain-induced arrhythmias in guinea pigs. Most of the synthesized compounds showed the antiarrhythmic activity in this primary screening system. Some of the compounds with 2-(N,N-dimethylamino)ethyl, 2-(pyrrolidin-1-yl)ethyl and 2-oxo-2 (morpholin-4-yl)ethyl moieties on the 5-position of 1,2,5-benzothiadiazepin-4(5H) one 1,1-dioxide exhibited a potent antiarrhythmic activity. The structure activity relationship of these compounds was discussed. PMID- 1446367 TI - Inhibitors of prostaglandin biosynthesis from Dalbergia odorifera. AB - The root heartwood of Dalbergia odorifera T. Chen (Leguminosae) is a Chinese medicinal drug (Japanese name koshinko) used for a stagnant blood syndrome (stagnation of disordered blood; Japanese, oketsu). In addition to 10 known compounds, five new phenolic compounds, isomucronustyrene and hydroxyobtustyrene (cinnamylphenols), (+)-isoduartin (isoflavan), odoriflavene (isoflav-3-ene) and ( )-odoricarpan (pterocarpan) were isolated and their structures were elucidated on the basis of chemical and spectroscopic methods. Of the fifteen compounds isolated, cinnamylphenols, isoflavans, isoflavene and benzoic acid derivative significantly inhibited prostaglandin biosynthesis as well as platelet aggregation induced by arachidonic acid. PMID- 1446368 TI - Studies on absorption, distribution, excretion and metabolism of ginseng saponins. VIII. Isotope labeling of ginsenoside Rb2. AB - To clarify the pharmacokinetics of absorption, distribution and excretion of ginsenoside Rb2 (Rb2), one of the major saponins of the root of Panax ginseng, following oral administration to rats, a tritium (3H) labeling of Rb2 was examined. The C-12 position of Rb2 was labeled with 3H-sodium borohydride (3H NaBH4) and 12-3H Rb2 and 12-3H-epi Rb2 was synthesized. This method of specific position labeling of Rb2 may be applicable to other ginsenosides. In the near future, the pharmacokinetics of Rb2 in rats may be clarified with 3H labeled Rb2. PMID- 1446369 TI - Changes in enzymatic and membrane-adsorbing activities of sphingomyelinase from Bacillus cereus by modification with a polyethylene glycol derivative. AB - Sphingomyelinase (SMPLC) from Bacillus cereus was modified with a polyethylene glycol (PEG) derivative, methoxypolyethylene glycol-succinimidyl succinate (ss PEG). The molecular weight of the ss-PEG-modified SMPLC was calculated to be approx. 150 kDa by gel-filtration whereas that of the native enzyme, was 25 kDa. By this modification, the enzyme increased its thermostability and retained its hydrolytic activity toward 2-(N-hexadecanoylamino)-4-nitrophenylphosphocholine (HNP) and sphingomyelin (SM) in the mixed micelles with the surfactants such as Triton X-100 and sodium deoxycholate (SDC). However, the activity toward liposomal SM was significantly decreased, and all the enzyme activities toward bovine erythrocytes, including membraneous SM-hydrolyzing and hemolytic activities as well as the enzyme adsorption onto the erythrocyte membranes, were completely lost. PMID- 1446370 TI - Effect of metal ions on transcription of the ada gene which encodes O6 methylguanine-DNA methyltransferase of Escherichia coli. AB - The effect of metal ions on transcription of the ada gene of Escherichia coli which is promoted by Ada protein in the presence of methylated deoxyribonucleic acid (DNA) was examined in a reconstituted system. Their effect on the O6 methylguanine-DNA methyltransferase (MGTase) activity of Ada protein was also examined. Ag+, Cd2+, Cu2+ and Hg2+ severely inhibited transcription of the ada gene at a dose which inhibited neither transcription of the lacUV5 gene nor MGTase activity. Zn2+ inhibited both transcription and MGTase activity in the same dose range. Al3+ and Fe3+ inhibited transcription of both ada and lacUV5 genes without affecting the MGTase activity of Ada protein. Inhibitory mechanisms are discussed. PMID- 1446371 TI - Core structure of glycyrrhizan GA, the main polysaccharide from the stolon of Glycyrrhiza glabra var. glandulifera; anti-complementary and alkaline phosphatase inducing activities of the polysaccharide and its degradation products. AB - The controlled Smith degradation and limited hydrolysis of glycyrrhizan GA, a representative polysaccharide with remarkable phagocytosis-enhancing activity isolated from the stolon of Glycyrrhiza glabra L. var. glandulifera Reg. et Herd. were carried out. Methylation analyses of the primary and the secondary Smith degradation products and of the limited hydrolysis product indicated that the core structural features of glycyrrhizan GA include a backbone chain composed of beta-1,3-linked D-galactose residues. Three-fifths of the galactose units in the backbone carry side chains composed of beta-1,3- and beta-1,6-linked D-galactosyl residues at position 6. Anti-complementary and alkaline phosphatase-inducing activities of the polysaccharide, periodate oxidation-reduction and the controlled Smith degradation products were investigated, and the controlled Smith degradation product showed significant activity. PMID- 1446372 TI - Application of microdialysis for study of caffeine distribution into brain and cerebrospinal fluid in rats. AB - The usefulness of microdialysis was examined for the chronological determination of caffeine concentration in the brain and cerebrospinal fluids (CSF) following intravenous administration of caffeine in rats. The recovery percent of caffeine by microdialysis, the concentration ratio of caffeine in the dialysate against that in the brain tissue or CSF was determined. The recovery percent was proved to be constant at 5 different steady-state plasma concentrations of caffeine (0.1 280 nmol/ml) and in different collecting periods of dialysate ranging from 30 s to 10 min. The mean recovery percent in the brain and CSF were 10.9 and 13.1%, respectively. Thus, microdialysis was proved useful for determination of drug concentration in the tissue and biological fluids with time resolution of more than 30 s. The microdialysis method was then applied for the chronological determination of caffeine concentration in the brain and CSF following intravenous bolus administration. The estimated caffeine concentration in the brain and CSF was the same as those obtained by direct determination in isolated brain and CSF, respectively. Transfer of caffeine from plasma to brain and CSF were further pharmacokinetically analyzed using a modified 2-compartment model. In this kinetic model, the transfer of caffeine between the CSF and brain was neglected, since the mutual transfer of caffeine was not detected in in vivo experiments. Calculated curves were well fitted on observed caffeine concentrations in the plasma, brain and CSF. PMID- 1446373 TI - Plasma alpha 1-acid glycoprotein concentration in rats with chemical liver injury. AB - The influence of liver injury on the plasma concentrations of alpha 1-acid glycoprotein (AGP) and albumin was examined in several different models of chemically-induced liver injury. The plasma AGP concentration in carbon tetrachloride (CCl4), allyl alcohol, bromobenzene, acetaminophen or N nitrosodimethylamine-induced liver injury was increased to 2-3.5 times the normal level at 24 h after the intoxication. The plasma AGP concentration was unchanged in ethionine-induced liver injury and was markedly decreased in galactosamine induced injury. The plasma albumin concentration was significantly decreased by the damage due to galactosamine, allyl alcohol or N-nitrosodimethylamine-induced liver injury, while no influence was observed by other hepatotoxin-induced liver injury. The plasma protein binding of propranolol was also determined in relation to the plasma concentrations of AGP and albumin in all the experimental models. Propranolol binding, expressed as bound to free ratio, showed a good correlation with the AGP concentration (r = 0.940; p < 0.001), but not with the albumin concentration. PMID- 1446374 TI - Syntheses of 2-chloro-4-nitrophenyl beta-D-maltopentaosides with bulky modification and their application to the differential assay of human alpha amylases. AB - Four novel maltopentaosides, 2-chloro-4-nitrophenyl O-(6-O-p-toluenesulfonyl alpha-D-glucopyranosyl)-(1-->4)-tris[O- alpha-D-glucopyranosyl-(1-->4)]-beta-D glucopyranoside (4), 2-chloro-4-nitrophenyl O-[6-O-(tert-butyldimethyl)silyl alpha-D- glucopyranosyl]-(1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D- glucopyranoside (5), 2-chloro-4-nitrophenyl O-[6-deoxy-6-(phenyl)sulfonyl-alpha-D glucopyranosyl]-(1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D- glucopyranoside (10), and 2-chloro-4-nitrophenyl O-(6-deoxy-6-phthalimido-alpha-D glucopyranosyl)- (1-->4)-tris[O-alpha-D-glucopyranosyl-(1-->4)]-beta-D glucopyranoside (11) were synthesized. Substrates 4, 5, 10, and 11 were hydrolyzed by human pancreatic alpha-amylase (HPA) from 1.1 to 2.9-fold faster than by human salivary alpha-amylase (HSA). Taking advantage of the difference in the hydrolytic rate of 5 (2.9-fold faster), we developed a new method for the differential assay of these two human alpha-amylases. PMID- 1446375 TI - Synthesis and antiplatelet activities of N-arylmethyl-3,4-dimethylpyrano[2,3 c]pyrazol-6-one derivatives. AB - A series of new 1- and 2-arylmethyl-3,4-dimethylpyrano[2,3-c]pyrazol-6-one derivatives were synthesized and examined for their antiplatelet activities. Some of these compounds showed significant inhibitory activities. Among them, 1 phenylmethyl-3,4-dimethylpyrano[2,3-c]pyrazol-6(1H)-one (4a), 2-(2' methoxyphenyl)methyl-3,4-dimethylpyrano[2,3-c]pyrazol-6(2H)- one (3e) and 2-(3' methoxyphenyl)methyl-3,4-dimethylpyrano[2,3-c]pyrazol-6-(2H) - one (3f) were the most effective. These inhibitors acted in a concentration-dependent manner. The antiplatelet effect of compound 3f is due to the inhibition of thromboxane A2 formation and the blockade of thromboxane A2/prostaglandin endoperoxide receptor in washed rabbit platelets. PMID- 1446376 TI - Synthesis of a dibenz[b,e]oxepin-bovine serum albumin conjugate for radioimmunoassay of KW-4679 ((Z)-11-[3-(dimethylamino)propylidene]-6,11- dihydrodibenz[b,e]oxepin-2-acetic acid hydrochloride). AB - (Z)-11-[3-(Dimethylamino)propylidene]-2-(methoxycarbonyl)methyl-6, 11- dihydrodibenz[b,e]oxepin-9-acrylic acid (5) was prepared for application to the radioimmunoassay of KW-4679 (1, (Z)-11-[3-(dimethylamino)propylidene]-6,11 dihydrodibenz[b,e ] oxepin-2-acetic acid hydrochloride). The acrylic acid moiety in the 9-position of 5 was employed for coupling with an amino group of bovine serum albumin (BSA) to provide 17. Subsequently, the conjugate 17 was treated with aqueous NaOH to hydrolyze the terminal methoxycarbonyl group in the 2 position of the BSA conjugated 5. Antiserum raised against the antigenic BSA conjugate 4 finally obtained was specific for 1. PMID- 1446377 TI - Biologically active complexes of nickel(II), copper(II) and zinc(II) with Schiff base ligand derived from the reaction of 2-aminopyridine and pyrrol-2 carboxaldehyde--their synthesis and characterisation. AB - A new Schiff-base ligand N-(2'-pyrrylmethylidene)2-aminopyrimidine derived from the reaction of 2-amino pyrimidine and pyrrol-2-carboxaldehyde and its nickel(II), copper(II) and zinc(II) complexes have been synthesised and characterised on the basis of elemental analysis, molar conductance, infrared, electronic and proton nuclear magnetic resonance (1H-NMR) and magnetic susceptibility data. The ligand and its complexes when screened for antibacterial activity against bacterial species such as, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. In all cases, the activity substantially increased on complexation with metals. PMID- 1446378 TI - Precolumn derivatization of nucleotides based on fluorescent carbamate formation of the sugar moieties in high-performance liquid chromatography. AB - The fluorescence derivatization of nucleotides with 2-(5-chlorocarbonyl-2 oxazolyl)-5,6-methylenedioxybenzo++ furan in the presence of sodium azide and the separation of the derivatives by high-performance liquid chromatography are described. The reagent reacts with 5'-terminal hydroxyl groups of nucleotides to produce the corresponding fluorescent carbamates. The derivatives of mono- and oligonucleotides are separated by chromatography on a reversed phase column (TSKgel ODS-80TM) and the derivatives of octa- and deca-nucleotides on a size exclusion column (TSKgel G3000SWXL). The detection limits (signal-to-noise ratio = 3) are 0.8-6.0 pmol on column. 5'Phosphorylated nucleotide also gives a fluorescent derivative after alkaline phosphatase-mediated dephosphorylation. PMID- 1446379 TI - Heat induced conformational changes generate mitogenicity to splenocytes by sclerogen from Sclerotinia sclerotiorum IFO 9395. AB - The fungal mitogen, sclerogen, obtained from sclerotia of Sclerotinia sclerotiorum IFO 9395 showed significant mitogenic activity to murine splenocytes after heat denaturation in relation to polymerization. To evaluate the conditions generating mitogenicity, we performed several chromatographic and spectral analyses. After heat denaturation of sclerogen, significant reduction of intrinsic fluorescence, significant changes on the ultraviolet absorption spectrum, significant changes on the circular dichroism spectrum, and an extreme change of the surface charge to anionic, were observed. These results strongly suggested that local as well as overall conformational changes of sclerogen associated with a high molecular mass and polyanionic charges are important in generating mitogenicity to murine splenocytes. PMID- 1446380 TI - Mannan-coated liposome delivery of gadolinium-diethylenetriaminepentaacetic acid, a contrast agent for use in magnetic resonance imaging. AB - Gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), a paramagnetic contrast agent for use in magnetic resonance imaging (MRI) was bound to stearylamine and incorporated into the liposomal membranes (Gd-DTPA liposomes). In addition, the Gd-DTPA liposomes were coated with mannan (cholesterol-aminoethylcarbamylmethyl mannan), a polysaccharide, to obtain the mannan-coated liposomes. An in vitro MRI study showed that the Gd-DTPA liposomes produced a greater intensity of contrast than did the Gd-DTPA solution with a reduced T1 relaxation time. Intravenous injection of the Gd-DTPA liposomes containing 153Gd or liposomes containing 153Gd or 14C-DTPA to mice showed an accumulation of Gd-DTPA primarily in the liver and lung. When the mannan-coated liposomes were administered, an increased uptake of Gd-DTPA by these tissues was demonstrated. The mannan-coated liposomes may enhance contrast of the liver in MRI at a lower dose of Gd-DTPA. PMID- 1446381 TI - Effect of oral pretreatment with antibiotics on the hydrolysis of salicylic acid tyrosine and salicylic acid-methionine prodrugs in rabbit intestinal microorganisms. AB - We examined the hydrolysis mechanism of salicylic acid-tyrosine (salicyl tyrosine) and salicylic acid-methionine conjugate (salicyl-methionine) in rabbits by exploring their behavior following intraduodenal and intracecal administration (72 and 36 mumol/kg, respectively: salicylic acid equivalent). A large amount of salicyl-methionine was absorbed following intraduodenal administration of salicyl methionine, without being metabolized to salicylic acid in the small intestinal mucosa. On the contrary, salicylic acid was detected in the blood following intraduodenal administration of salicyl-tyrosine, suggesting that salicyl tyrosine was metabolized in the small intestinal mucosa. After oral pretreatment of rabbits with kanamycin sulfate (6 x 400 mg) or tinidazole (6 x 160 mg), the hydrolysis of salicyl-tyrosine and salicyl-methionine following intracecal administration was inhibited significantly, indicating that the intestinal microorganisms were responsible for the biotransformation of these prodrugs. Furthermore, in rabbits orally pretreated with both kanamycin sulfate and tinidazole, a significant inhibition of salicylic acid formation from salicyl tyrosine and salicyl-methionine following intracecal administration was observed. PMID- 1446382 TI - Synthesis of new fluorescent nucleosides, 3-beta-D-ribofuranosylpyrazolo (3,2-i) purine derivatives and their cytotoxic activities. AB - The novel nucleosides 3-beta-D-ribofuranosylpyrazolo(3,2-i) purine (8) and their 9-substituted bromo, nitro and amino compounds (3, 6 and 11) have been prepared from a fully protected 3-beta-D-ribofuranosyl(3,2-i)purine-9-carboxyamide 1 by bromodeamidation (ipso bromination). Compounds 3, 8 and 11 exhibited antileukemic activity against mouse leukemia L5178Y cells in culture, while the 9-substituted nitro, ester and amide compounds (6, 12 and 13) showed no cytotoxicity. PMID- 1446383 TI - Phagocytic cell function in recurrent endotoxemia in sheep. AB - Sepsis syndrome in severely traumatized patients is supposedly due to a blockade of the phagocytic cell system--for example, the reticulo endothelial system (RES) and polymorph nuclear leukocytes (PMNL), which cause insufficient elimination of bacterial substances (e.g., endotoxin). In contrast we found in a previous study using a model of acute endotoxemia that RES clearance is enhanced, while PMNL function gave evidence for decompensation. In order to clarify whether or not our results were just a matter of single dose endotoxemia, we have investigated RES and PMNL function in a sheep model with recurrent endotoxemia. A sheep receiving endotoxin at a dose of 1 microgram/kg body weight every 12 hours was monitored over a 5-day period. RES clearance was calculated by the half-life of Tc99 phytate each day. The PMNL function was determined by measuring chemiluminescence (CL) of isolated PMNL and total blood. The half-life of Tc99 phytate decreased from 56 min to 44 min with endotoxin (P less than or equal to 0.01) the second day and further to 42 min (P less than or equal to 0.002) on the third day. Values then returned to baseline until the end of study. Zymosan induced and luminol enhanced CL response indicated an acute cellular exhaustion after the first endotoxin dose. Under subsequent endotoxin administration, a daily attenuation of the acute response was noted in combination with baseline opsonin capacity. Our results give evidence that also in recurrent endotoxemia RES function is characterized by a sufficient clearance, whereas the PMNL function remains decreased and therefore possibly is responsible for the well-known clinical post-traumatic septic complications. PMID- 1446384 TI - A novel xanthine derivative counteracting in vivo tumor necrosis factor alpha toxicity in mice. AB - The xanthine derivative A 802715 (1-(5-hydroxy-5-methyl)hexyl-3-methyl-7- propyl xanthine, Hoechst AG) caused dose-dependent protection against lipopolysaccharide (LPS)-induced lethal shock in mice. In animals which had received the compound, the LPS-induced increase of serum tumor necrosis factor (TNF alpha) levels was not significantly affected. Protection against LPS-induced lethality was observed not only when A 802715 was given 1 hr before or simultaneously with LPS but also when administered 1 hr after LPS challenge. Administration of 200 mg/kg of the compound 1 hr before challenge also fully protected against lethal shock induced by intravenous administration of recombinant murine TNF alpha. It is concluded that A 802715 counteracts TNF alpha toxicity and that the drug bears the potential of therapeutic intervention in septic shock. PMID- 1446385 TI - Pyrimidine-enhanced purine uptake in hepatocytes and improved survival from hypovolemic shock. AB - To assess the effect of pyrimidines on the incorporation of purines into rat hepatocytes, monolayer preparations of hepatocytes were incubated with radiolabeled precursors and their uptake determined. The uptake of purine precursors (inosine monophosphate, inosine, and hypoxanthine) was 27.8 +/- 1.31 nmoles per well, per 30 min. In the presence of added pyrimidines (uridine monophosphate, uridine, and orotate), this increased by 22%. Further enhancement (45%) was observed when L-dihydroxyphenylalanine (L-DOPA) plus pyridoxal-5' phosphate was added to the purine/pyrimidine incubation medium. The effect of increased uptake of purines on survival after hypovolemic shock was also studied. Rats were bled to a blood pressure of 40 mmHg for 105 min and then treated with return of shed blood plus saline with or without purines and pyrimidines. Survival at 24 hr was 43% (15/35) in control animals, 66% (8/12) (P = 0.276) when treated with inosine monophosphate (IMP) and aspartate (60 mumoles/kg each), and 83% (10/12) (P = 0.037) for IMP with aspartate and orotate treatment (60 mumoles/kg each). Thus, the addition of orotate enhanced survival possibly by promoting salvage or by uptake of purines. Nucleotide concentrations in the livers of animals after shock which had received IMP and orotate demonstrated a return of both ATP and energy charge to normal, further indicating the value of this treatment. PMID- 1446386 TI - Kinin metabolism in the perfused ventilated rat lung. II: Influence of ventilation, perfusion, and perfusate composition variation on bradykinin metabolism in uninjured lung. AB - Bradykinin metabolism by peptidases of the pulmonary endothelium has been investigated in the previously uninjured, ventilated, and asanguinously perfused rat lung. The influence of short-duration (up to 20 min) abnormal ventilation and perfusion conditions on bradykinin metabolism was assessed. Neither variation of the oxygen concentration (0 to 45%) nor omission of carbon dioxide in the ventilatory gas altered bradykinin metabolism significantly. Tidal volume variation did not alter bradykinin metabolism, and exclusion of one lung from the perfusion circuit reduced the capacity to degrade bradykinin proportionately. Acidification of the perfusion medium to pH 5 did not alter bradykinin metabolism. Acetylsalicylic acid in the perfusate protected the lung from an otherwise irreversible pressure increase associated with high-dose bradykinin perfusion. Endotoxin and hydrogen peroxide in the perfusate did not alter bradykinin metabolism. However, ammonia in the ventilatory gas caused immediate pulmonary edema, diminished lung capacity to metabolize bradykinin and altered the pattern of bradykinin metabolic products. The pulmonary endothelium itself, in the absence of blood, maintains its capacity to metabolize bradykinin under an extraordinary range of conditions. PMID- 1446387 TI - Pentoxifylline treatment of sepsis in conscious Yucatan minipigs. AB - Recent evidence suggests that pentoxifylline (PTX) may be useful in the treatment of sepsis. We examined effects of PTX in a conscious swine model of sepsis. Yucatan minipigs (20-30 kg) were anesthetized and instrumented with catheters in the vena cava, aortic arch, pulmonary artery (Swan-Ganz thermodilution catheter), and peritoneum. Twenty-four hours after surgery, sepsis was induced by intraperitoneal (ip) injection of Escherichia coli bacteria (2 x 10(10) cfu/kg). Nonseptic pigs received intraperitoneal saline (5 ml/kg). PTX treatment (3 mg/kg/hr, iv; 1 mg/ml in 0.9% saline) and maintenance fluid (5 ml/kg/hr, iv) were started with bacterial infusion. An additional 60 cc/kg 0.9% saline bolus was administered iv at 1 hr. Pigs were monitored before and 1, 2, 5, and 24 hr after bacterial injection. Intraperitoneal injection of bacteria led to significant reductions in blood pressure and cardiac output and elevations in pulmonary wedge pressure and pulmonary vascular resistance. These effects were attenuated by PTX treatment. All septic animals demonstrated elevated creatinine, blood urea nitrogen, circulating endotoxin (LPS), and tumor necrosis factor concentrations, reductions in white blood cell and platelet counts, and peritonitis. None of these responses was altered by PTX treatment. We conclude that PTX may prove to be a useful therapeutic tool in the early treatment of septic shock but is limited in the scope of its effects. PMID- 1446388 TI - Beneficial effects of SK&F 105809, a novel cytokine-suppressive agent, in murine models of endotoxin shock. AB - SK&F 105809 is a structurally novel dual inhibitor of lipoxygenase and cyclooxygenase-mediated arachidonic acid (AA) metabolism, which has demonstrated antiinflammatory activity in rodent models of inflammation. In addition, the active metabolite of this compound, SK&F 105561, has been shown in vitro to inhibit the production of the inflammatory cytokine interleukin-1 (IL-1) in human monocytes stimulated with lipopolysaccharide (LPS). We report here that in vitro SK&F 105561 also blocks the production of tumor necrosis factor (TNF) from human monocytes (IC50 0.8-3 microM). Furthermore, in a murine model of endotoxin shock in which animals are injected with LPS in combination with D-galactosamine (D gal), SK&F 105809 (10, 30, and 100 mg/kg p.o.), delivered 30 min prior to LPS/D gal, caused a dramatic reduction in serum TNF (40-90%) and protected the animals from the lethal effects of this treatment. Similar results were obtained in a second model of endotoxin shock in which mice were sensitized with Propionibacterium acnes 10 days prior to LPS injection. In this system 100-fold higher levels of serum TNF are elicited than with the LPS/D-gal model. Treatment with SK&F 105809 (30 and 100 mg/kg p.o.) delivered 30 min prior to LPS resulted in 90-100% inhibition of serum TNF. Protection from the lethal effects of LPS was observed at these doses in the P. acnes/LPS model. PMID- 1446389 TI - Role of the L-arginine-nitric oxide pathway in the changes in cerebrovascular reactivity following hemorrhagic hypotension and retransfusion. AB - We studied the involvement of the L-arginine-nitric oxide pathway in the changes in cerebrovascular reactivity following hemorrhagic hypotension and retransfusion. Feline middle cerebral arteries were prepared from control animals killed under anesthesia and from anesthetised animals subjected to hemorrhagic hypotension (stepwise bleeding to 90, 70, and 50 mmHg, maintained for 20 min at each level) followed by retransfusion (20 min). Two-mm-long vessel segments were suspended in organ chambers containing Krebs-Henseleit solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurements. Contractions to noradrenaline (norepinephrine), relaxations to acetylcholine, ATP, adenosine, and SIN-1, a nitric oxide donor compound, were compared in the vessels of the control and hemorrhage-subjected animals. Contractile responses to noradrenaline were significantly enhanced after hemorrhage, whereas relaxations to acetylcholine, ATP, and adenosine were significantly reduced. Relaxations to SIN-1, however, remained unchanged. L-Arginine did not cause relaxations in control vessels but relaxed the arteries after hemorrhage and retransfusion. To clarify the involvement of the L-arginine-nitric oxide pathway in these alterations, we studied the effect of exogenous application of L-arginine, the precursor of endothelium-derived relaxing factor (EDRF) and NG-nitro-L-arginine (NOLA), a competitive antagonist of the EDRF-producing enzyme on the vascular responses in vitro. Similar to the effect of hypotension and retransfusion, NOLA enhanced the noradrenaline-induced contractions and inhibited the acetylcholine-induced and purinoceptor-mediated relaxations in the control arteries. In the control vessels in vitro, L-arginine treatment did not modify any contractile or relaxant response. At the same time, in vitro L-arginine treatment inhibited the hemorrhagic hypotension-induced enhancement of the contractions to noradrenaline and restored the diminished relaxations to acetylcholine (but not to ATP or adenosine). In the vessels after hemorrhage, NOLA neither further enhanced the already markedly enhanced noradrenaline-induced contractions nor further inhibited the relaxations caused by ATP and adenosine. In the case of acetylcholine, however, NOLA caused a further inhibition of the relaxations. The effect of in vivo L-Arg infusion (30 mg/kg initial bolus and 10 mg/kg/min infusion) during hemorrhagic hypotension and retransfusion on the in vitro vascular reactivity was similar to that of the in vitro L-arginine treatment. The present study demonstrates that even short-lasting hemorrhagic hypotension combined with retransfusion markedly inhibits nitric oxide-mediated, agonist induced endothelium-dependent cerebrovascular responses. In vivo or in vitro L arginine treatment is able to restore normal responses to some agents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446390 TI - Effect of alpha-adrenergic blockage on cellular Ca2+ during endotoxic shock. AB - The effect of alpha-adrenergic receptor antagonists, phentolamine, and prazosin on cytosolic Ca2+ concentration, [Ca2+]i, was studied in hepatocytes during endotoxic shock. Rats were given intravenous injections of endotoxin (20 mg/kg), phentolamine (3 mg/kg) plus endotoxin (20 mg/kg), or prazosin (5 mg/kg) plus endotoxin (20 mg/kg). They were sacrificed 5 hr later, at which time the endotoxin-injected rats showed signs of shock. Isolated hepatocytes were prepared and employed for the measurement of [Ca2+]i under basal and hormone-stimulated (1 and 10 microM epinephrine) conditions by means of Quin 2 fluorescence technique. The apparent basal level of [Ca2+]i in endotoxic rat hepatocytes (mean +/- SE: 482 +/- 31 nM) was significantly higher (P less than 0.05) than in phentolamine plus endotoxin (242 +/- 73) and prazosin plus endotoxin (240 +/- 43) groups. A significant increase in hepatocyte [Ca2+]i occurred with epinephrine in the phentolamine plus endotoxin and prazosin plus endotoxin groups, but not in the group receiving endotoxin alone. Endotoxic rats showed a mortality rate of 75%, whereas phentolamine plus endotoxin and prazosin plus endotoxin groups showed a mortality rate of 38% and 20% respectively. These data suggest that the protective effect of alpha-adrenergic receptor antagonists during endotoxic shock may be mediated, in part, by attenuating the entrance of Ca2+ into endotoxic liver cells. PMID- 1446391 TI - Cardiovascular response in canine endotoxic shock: effect of ibuprofen pretreatment. AB - Ibuprofen pretreatment increases arterial pressure and reduces mortality in endotoxic dogs. The increase in arterial pressure may be caused by increases in arterial resistance, arterial sphincter tone, or both. Thus it is not clear if ibuprofen pretreatment prevents the hemodynamic effects of endotoxemia or merely masks such effects by producing concomitant increases in arterial resistance. Accordingly, this study was performed to determine the effects of ibuprofen pretreatment on arterial pressure-flow relations and other measures of cardiovascular function in a canine model of endotoxic shock. In 19 pentobarbital anesthetized and splenectomized, closed-chest dogs, biventricular stroke volumes were measured with electromagnetic flow probes, and intrathoracic vascular and pleural pressures were measured with catheters. Instantaneous venous return curves (see Pinsky MR, J Appl Physiol 56:765, 1984) were generated during positive-pressure ventilation, and steady-state arterial pressure-flow relations, left ventricular function, peripheral vascular compliance, oxygen consumption/oxygen delivery ratio, and arterial blood lactate levels were measured during two sequential volume loading and removal (20 ml/kg) sequences. All but two dogs received a bolus infusion of Escherichia coli endotoxin (2 mg/kg) between the two fluid challenge runs. Eleven of the 17 endotoxic dogs also received ibuprofen (15 mg/kg) immediately before the initial fluid challenge. Ibuprofen pretreatment abolished all hemodynamic effects of endotoxin, whereas in the untreated group endotoxin caused decreases in calculated arterial outflow pressure and in peripheral vascular capacitance. Oxygen consumption remained constant despite changes in oxygen delivery in the nonendotoxic dogs and in the ibuprofen-pretreated dogs, whereas oxygen consumption covaried with oxygen delivery in the endotoxic dogs not pretreated with ibuprofen. Arterial lactate levels were higher after endotoxin infusion (2.1 +/- 0.5 to 3.1 +/- 0.6 mmol/liter; P less than 0.05 pre- to postvolume) but were not different between treatment groups. These data suggest that ibuprofen alters many, but not all, of the hemodynamic effects of endotoxin infusion in the dog. PMID- 1446392 TI - Malpractice in obstetrics: a contribution of cases in southern Italy. AB - Looking ahead to the abolition of many intra-European frontiers the Authors offer this contribution to the discussion of the medico-legal aspects of gynecological activity in the United Europe of 1993. It is to this end that they present the data from a review of the material which has been the subject of litigation on the part specialists in Southern Italy, also commenting on the case series in the light of the Italian provisions in force up to date. PMID- 1446393 TI - Retroperitoneal abscess and vena cava thrombosis following normal pregnancy and delivery. AB - A 24 year old primigravida underwent a normal pregnancy and delivery, and developed a retroperitoneal abscess and thrombosis of the vena cava late in the puerperium. A transvaginal drainage of the abscess was performed and the thrombosis of the vena cava treated with Heparin and thrombectomy. Full recovery was obtained. PMID- 1446394 TI - Eicosanoid production in human umbilical cord vessels: effect of 17 beta estradiol. AB - This study was designed to investigate the effects of 17 beta-estradiol on prostanoid formation from exogenous arachidonic acid in homogenates of human umbilical cord vessels. The veins produced more prostanoids than the arteries and predominantly 6-keto-PGF1 alpha. 17 beta-estradiol had no effect on the rate of production of prostanoids in either vessels. Thus, at least in our in vitro system, the regulation of the vascular tone by prostanoids seems not to be altered by the addition of 17 beta-estradiol. PMID- 1446395 TI - A case of segmental renal dysplasia incidentally discovered in an 18 year old woman during a gynecological surgical operation. PMID- 1446396 TI - Variations of lymphocyte sub-populations in vulvar condylomata during therapy with beta-interferon. AB - Several experiences induced us to consider genital HPV infection as an expression of a local immunodeficiency. The aim of our study was to research the effect of immunotherapy on the lymphocyte subpopulations and Langerhans cells in vulvar condyloma. Twenty women with persistent vulvar condylomata, treated with 2,000,000 IU/die of beta-interferon for 15 days, were submitted to vulvar biopsy before and 2-5 months after medical treatment. The frozen sections obtained were assayed with the following monoclonal antibodies: OKT4 (T helper lymphocytes), OKT8 (T suppressor lymphocytes), OKB7 (B lymphocytes) and S-100 protein (Langerhans cells). Using a morphometric evaluation, the average number of both intraepithelial and stromal lymphocyte subsets and of the intraepithelial Langerhans cells was assessed. In all the biopsies preceding the medical treatment we found a low number of T helper lymphocytes both in the epithelium and stroma, with inversion of T4/T8 lymphocyte ratio and rare presence of Langerhans cells. In patients with a good therapeutic response (50-100% of condyloma reduction) we observed an increase in intraepithelial T4 lymphocytes and a decrease in both intraepithelial and stromal T8 lymphocytes. In cases with persistent disease after therapy, the histological pattern was similar to that observed in the first biopsy, with the exception of a significant increase in the average number of Langerhans cells. Our data correlate the clinical response to the immunotherapy with the histology of lymphocyte subsets in the vulvar condylomata. The increase in Langerhans cells observed in patients with negative response may be interpreted with a probable inability of these cells to promote the immune reaction. PMID- 1446397 TI - Myometrial hypertrophy and uterine metropathy without apparent organic cause: rate or responsibility. AB - Between 1971 and 1980 more than 6,000,000 hysterectomies were performed in the USA. Dysfunctional uterine hemorrhage with non tumoral uterus and hypertrophic characteristic has been one of the principal indications, without possibility of definition as a pathological entity with its own characteristics. With all these premises the Authors have attempted to see, by means of morphometric studies, the myocyte characteristics and the proportion and composition of the uterine wall and at the same time eventual hormone-dependence of this phenomenon. For this they turn to to determination of oestrogen and progesterone receptors. PMID- 1446398 TI - Carcinoma of the vulva: critical analysis of survival and treatment of recurrences. AB - Prognostic variables in vulvar cancer include: stage, lymph nodal status, tumour diameter, vascular space invasion, depth of invasion. Treatment must in the cost/benefit balance, be adequate to these prognostic variables and surgery is today the cornerstone in vulvar cancer management. In early stages it is possible to control the disease with personalized radical non-mutilant operations limiting the high incidence of complications of the past, without endangering the 5-year survival rate. The risk of relapses is related to some factors such as site of tumour growth, depth of tumoural infiltration, lymphnode involvement and vascular space involvement. Relapses appear earlier in the groin than in the primitive sites and cases with more than 3 effected nodes have a higher incidence of recurrences in any site. Survival in related to localization and time of relapses. The treatment of recurrence is personalized for different sites, almost always surgical, in local recurrences. PMID- 1446399 TI - A comparative study of propofol and thiopental as induction agents for elective caesarean section. AB - Twenty women for elective caesarean section received either propofol 2.3 mg/kgr or thiopental 4.4 mg/kgr for induction of general anaesthesia. Maintainance was similar for both groups. Mean arterial pressure and heart rate were recorded non invasively before anaesthesia, during intubation, one and five minutes after intubation. There were no significant differences in haemodynamic response between the two groups. During intubation heart rate rose in both groups, but remained increased five minutes after tracheal intubation only in the thiopental treated women (p less than 0.05). There was no significant neonatal depression as assessed by Apgar Scores and blood gas analyses. Propofol appears to be a suitable alternative to thiopental as an induction agent for obstetric anaesthesia. PMID- 1446400 TI - Secondary post-partum haemorrhage: a recurrent condition? PMID- 1446401 TI - Plasma and amniotic fluid concentration of fibronectin during normal and diabetic pregnancy. AB - Fibronectin is a plasma glycoprotein which is involved in coagulation, platelet function, tissue repair and the vascular endothelial basement membrane. To ascertain the influence of pregnancy on plasma concentrations of fibronectin, we qualified plasma concentrations of fibronectin in normal pregnant women during the first, second and third trimester; at the time of delivery; and on the third day post partum, using a radial immunodiffusion plate procedure. The concentrations of fibronectin found in these samples were compared with the concentration of fibronectin in 20 pregnancies complicated by diabetes. Mean plasma concentrations of fibronectin rose significantly through pregnancy and were significantly higher during delivery. A decrease in the concentrations was noticed on the third post partum day. An even more significant decrease of maternal plasma concentrations was noticed during cesarean section in normal pregnancies as compared to the concentrations found at the time of normal delivery. Of the diabetic group of women studied, higher concentrations of plasma fibronectin were found at the time of cesarean section than at the time of delivery. Maternal plasma concentrations of fibronectin were significantly greater than amniotic fluid and umbilical cord plasma concentrations. PMID- 1446402 TI - Evidence for gene-environmental interactions in Utah families with hypertension, dyslipidaemia and early coronary heart disease. AB - 1. Among 45,258 Utah families surveyed, about 4% have a strong aggregation of early coronary disease. In detailed clinical evaluation, about 21% of such high risk coronary families were found to have familial dyslipidaemic hypertension (FDH) and about 3% were found to have heterozygous familial hypercholesterolaemia (hFH). 2. Common and potentially modifiable environmental factors seem to play an important role in these high risk families. Non-genetic obesity promotes the expression of FDH. A high fat diet promotes the expression of FH. Cigarette smoking promotes earlier death in all coronary prone families. 3. Practical approaches are suggested for helping coronary prone pedigrees by applying our understanding of genetic and environmental factors that promote earlier coronary disease onset. PMID- 1446403 TI - Membrane fluidity as a genetic marker of hypertension. AB - 1. The purpose of the present study was to examine changes in membrane fluidity in hypertension by means of an electron spin resonance (ESR) and a spin labelling methods. 2. Erythrocytes from spontaneously hypertensive rats (SHR) and from patients with essential hypertension were examined and compared with those from age-matched normotensive controls. ESR spectra were obtained for a fatty acid spin label agent (5-nitroxide stearate) in the membranes. The values of outer hyperfine splitting (2T' parallel) and of order parameter (S) of the ESR spectra were significantly higher in erythrocytes from SHR and patients with essential hypertension than in those from normotensive controls. Similar results were obtained in cultured vascular smooth muscle cells of SHR. This finding shows that the membrane fluidity might be lower in SHR and in essential hypertension. 3. When Ca was loaded to erythrocytes with a Ca-ionophore (A23187), the parameters of the ESR spectra showed a greater increase (membrane fluidity was decreased) in SHR and in patients with essential hypertension than that in the normotensive controls. The Ca-induced alterations in membrane fluidity were not definitely observed in secondary hypertension. 4. These results suggest that the lower membrane fluidity might be a genetically determined abnormality of hypertension. The marked reduction of the membrane fluidity by Ca-loading in SHR and in essential hypertension might support the hypothesis that an abnormality of the Ca handling at cellular levels could affect physical properties of the biomembranes in genetic hypertension. PMID- 1446404 TI - Analysis of the apolipoprotein B3' hypervariable region in patients with essential hypertension. AB - 1. The typing of the apolipoprotein B 3' hypervariable region was investigated in hypertensive and normotensive subjects using rapid typing of a variable number of tandemly repeated short DNA sequences (VNTR) by the polymerase chain reaction. 2. In the DNA samples of 89 normotensive and 99 hypertensive patients, 13 different sized alleles were detected. The most frequent allele has 35 repeat units in both groups with frequencies of 0.624 and 0.596 in normotensive and hypertensive patients, respectively. Frequency distribution of 13 alleles was similar in both groups. 3. These results demonstrate no association between the apolipoprotein B gene polymorphism and essential hypertension. PMID- 1446405 TI - Salt and hypertension: revisited. AB - 1. There is only one known environmental factor that possibly could hold the key to much of the problem of 'essential' hypertension and this is salt. Without a high or moderately high salt intake, other environmental factors may be largely inoperative. The evidence, which still falls somewhat short of certainty, is briefly reviewed. PMID- 1446406 TI - Experimental studies on cardiovascular disorders and cellular Ca handling in shell-less chick embryos. AB - 1. Chick embryos rendered Ca deficient by long-term culture outside the eggshell develop hypertension/tachycardia. 2. In this study, the hypertension of the shell less (SL) chick embryo has been characterized by comparing their cardiovascular response to adrenergic drugs and cellular Ca handling function with normal (NL) embryos. 3. Before and after the administration of noradrenaline (NA), phentolamine (PA), isoproterenol (IP), and propranolol (PP), blood pressure and pulse rate were measured. 4. Baseline blood pressure was consistently higher in SL embryos. In both embryos, blood pressure was elevated by NA and PP, but lowered by IP and PA. Pharmacological sensitivity to NA and PA was higher in SL embryos. Serum Ca was lower in SL embryos, while myocardial calcium content was not different. At the cellular level, Ca handling was studied using red blood cells (RBC) from SL and NL embryos under varying osmotic and ionic conditions by analysing 45Ca uptake and cell volume regulation. 5. Two features of RBC Ca uptake were apparent: (i) Na-Ca exchange was functional since Ca uptake was dependent on external Na; (ii) Ca uptake was dependent on total ionic electrochemical gradient. The SL RBC had greater ion permeability, more active Na Ca exchange function and higher Ca pumping out capacity. 6. These systemic and cellular properties of the SL embryo indicate that it is a novel and useful experimental system to study the relationship between Ca homeostasis and the development of hypertension. PMID- 1446407 TI - Analysis of factors in hypertension: change of membrane fluidity in the arteries of spontaneously hypertensive and monocrotaline-injected rats. AB - 1. A change of membrane fluidity of a small piece of artery tissue was monitored by Fourier transform infra-red spectroscopy. 2. The measurement of carotid artery in situ revealed that a significant change in the peak position of the methylene absorbance was detected in the spontaneously hypertensive rat subjected to anoxia, but not in the Wistar-Kyoto rat carotid. The shift of a peak to the higher wavenumber position suggested that the averaged membrane fluidity of the artery was increased by the anoxic treatment. A similar change of membrane fluidity was also observed in a pulmonary hypertension induced by monocrotaline. 3. At 4 weeks after the injection of monocrotaline, the membrane fluidity was increased in the pulmonary artery tissue. 4. The change of membrane fluidity may be caused by the change of activity of phospholipases in the arteries with hypertension. PMID- 1446408 TI - The role of oxidized lipoproteins in the pathogenesis of atherosclerosis. AB - 1. Oxidized low density lipoprotein (LDL) has been suggested to play an important role in atherogenesis by facilitating the accumulation of lipids in macrophages. In vitro studies from this laboratory have shown that oxidized LDL is recognized not only by the specific receptor for it, but also by the receptor which is common for oxidized LDL and acetyl LDL. Probucol, originally developed as an antioxidant, prevents the oxidative modification of LDL in vitro. Recent studies by the authors show that probucol prevents the progression of atherosclerosis in homozygous Watanabe heritable hyperlipidaemic rabbits in vivo without any changes in plasma LDL cholesterol levels. 2. These results strongly suggest that oxidative modification of LDL could occur in vivo and probucol could slow the progression of atherosclerosis, without changes in plasma cholesterol levels. 3. In addition, recently the authors demonstrated that high density lipoprotein (HDL) particles are also oxidized. Once HDL particles were oxidized, they showed a lessened effect on the decrease of cholesteryl ester in foam cells, suggesting oxidative modification of HDL may stimulate development of atherosclerosis by limiting efflux of cholesterol from foam cells. Moreover, HDL particles from probucol-treated patients are hardly oxidized; subsequently, these HDL particles caused a marked efflux of cholesterol from foam cells. PMID- 1446409 TI - Gene-environment interaction in hypertension, stroke and atherosclerosis in experimental models and supportive findings from a world-wide cross-sectional epidemiological survey: a WHO-cardiac study. AB - 1. Genetic rat models of hypertension, such as spontaneously hypertensive rats (SHR) and in particular, stroke-prone SHR (SHRSP) are useful models for research on the genetic pathogenesis, gene-environment interaction and control of environmental factors for the prevention of hypertension and related cardiovascular diseases (CVD). 2. Since recent genetic analysis of hypertension in SHRSP indicated that one of the hypertensive genes related to salt-induced blood pressure (BP) rise was linked with the gene of the angiotensin-converting enzyme, gene-environment interaction is important in the humoral, neural, vascular and nutritional mechanisms of hypertension and CVD. 3. Extensive experimental studies in SHRSP by the authors have demonstrated nutritional factors counteracting directly or indirectly against the adverse effect of excess salt intake, such as K, Mg, Ca, dietary fibres, protein, some amino acids and fatty acids, etc.; they are therefore effective in preventing stroke, the typical complication of hypertension. 4. Experimental atherosclerotic models were established in SHRSP, which indicated also a gene-environment interaction in the pathogenesis of atherosclerosis at the cellular level of vascular smooth muscle cells. Excess salt intake accelerated cholesterol absorption from the intestine to induce arterial fat deposition as well as to active platelet aggregation by the mechanism of increased intracellular Ca2+ mobilization. 5. Based on such experimental findings on the hypertension and related CVD prevention, a cross sectional multicentre epidemiological 'CVD and Alimentary Comparison' Study (WHO CARDIAC Study) was designed to assess the relationship of biological markers of dietary factors with BP ('core' study) and major CVD mortalities ('complete' study) and has been successfully undertaken for the past 8 years in co-operation with 54 centres in 23 countries. 6. The results of 'core' study so far obtained by cross-centre simple linear regression analysis demonstrated adverse effects of body mass index and salt intake on BP in men and possible beneficial effects of Mg by within-centre multiple linear regression analysis. 7. Preliminary cross centre simple linear regression analysis of the 'complete' study indicated a positive correlation of serum cholesterol levels and negative correlation of serum phospholipid poly-unsaturated to unsaturated fatty acid ratios and 24 h urinary taurine excretion with coronary heart diseases mortality; a positive correlation of 24 h urinary Na and Na/K ratios and a negative correlation of serum cholesterol levels with stroke mortalities was indicated. 8. These epidemiological data confirmed mostly the applicability of experimental findings to the nutritional prevention of hypertension and CVD prevention.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446410 TI - Abnormal hsp70 gene expression: its potential key role in metabolic defects in hypertension. AB - 1. Abnormal heat stress gene hsp70 expression has been demonstrated in organs as well as in cultured cells from spontaneously hypertensive rats and mice. 2. The polymorphism of hsp70, which is localized in the major histocompatibility complex, appears to segregate with a significant portion of hypertension. 3. Abnormal hsp70 expression may lead to anomalies in its feedback regulation, particularly since the steady state level of heat stress protein HSP70 seems to be lower in hypertensive than in normal animals. 4. Another biological consequence could be a modification of the effectiveness of cortisol, which may be involved in metabolic components of the pathogenesis of hypertension. PMID- 1446411 TI - The association between salt sensitivity of blood pressure and family history of hypertension. AB - 1. The salt sensitivity index (SSI) and family history of hypertension were studied in 140 hospitalized patients with essential hypertension to clarify whether salt sensitivity of blood pressure is related to familial disposition to hypertension. 2. SSI was calculated by dividing the change of mean blood pressure by that of urinary sodium excretion when salt intake was restricted from 15 to less than 3 g/day. 3. Family history of hypertension was classified into three groups depending on the presence or absence of hypertension in the father, mother and siblings. 4. The group without a family history of hypertension showed a significantly lower SSI value than other groups. 5. In multiple regression analysis undertaken within each gender, SSI showed significant partial correlations with blood pressure and family history of hypertension in the female group (r = 0.402 and 0.265, respectively), whereas in the male group it showed a positive correlation only with blood pressure (r = 0.501). These results indicate that salt sensitivity of blood pressure is related to familial disposition to hypertension. This association was more apparent in the female than male group and its gender difference can be partially attributed to the fact that blood pressure in the female group is more sensitive to salt. PMID- 1446412 TI - Ethnic differences in salt sensitivity: genetic or environmental factors? AB - 1. The CARDIAC study, a world-wide cross-sectional epidemiological study on the relationship between alimentary factors and cardiovascular diseases, provided the initial evidence of ethnic differences in salt sensitivity; this was because despite much less urinary sodium excretion in Tanzania than in Brazil and the Japanese, the prevalence of hypertension was relatively higher in Tanzania than in the latter two populations. 2. To investigate this difference in salt sensitivity, a standardized clinical experiment was carried out: six to 13 male volunteers were placed on 2500 kcal basal diets containing 3 g salt/day. Eighteen grams of salt were added daily from the sixth to the 11th day in Tanzania and Brazil, while 22 g of salt were added in Japan. 3. Salt loading induced a significant rise in systolic blood pressure (SBP) on the second day of the high salt period (HSP) in Japan, the second and third day of HSP in Brazil, and all days of HSP in Tanzania. 4. Salt sensitivity was seen in 16.7% of the participants in Japan, 36.4% in Brazil and 46.2% in Tanzania. Further analysis of the effect of salt on blood pressure (BP) was carried out using the data from the CARDIAC study by multiple regression analysis. A within-centre comparison of fatty acid was also made. 5. The regression analysis revealed that the relationship of salt and blood pressure is more positively tight in Tanzania than Brazil and Japan after controlling for other confounding variables. Fatty acids in serum phospholipids contain significantly more palmitic acid and showed lower P/S ratios than those from Brazil and Japan. PMID- 1446413 TI - Quantitative analysis of the tracking of blood pressure and relative factors in childhood: Shimane Heart Study. AB - 1. In order to clarify the predictive factors of cardiovascular diseases caused by hypertension and hypercholesterolaemia in adults, a longitudinal epidemiological study was started in 1978. 2. This paper reports the results of research carried out from a quantitative analysis of the tracking of blood pressure and anthropometric parameters in children and adolescents using a tracking index. The index was calculated according to the changes in blood pressure quintiles for the whole population during the observation period. 3. The study population consisted of 5148 Japanese children living in the city of Izumo, who were examined every 3 years between the ages of 6 and 15 years old. 4. Although systolic blood pressure tracked weakly during childhood and adolescence, there was no significant relation between the tracking of systolic blood pressure and a family history of hypertension. 5. The tracking indices of the anthropometric parameters were better than those of systolic blood pressure, but the index of the left ventricular mass was similar to that of systolic blood pressure. 6. In conclusion the tracking of blood pressure might be determined by the tracking of bodyweight and height. PMID- 1446414 TI - Family history study on hypertension in Japan. AB - 1. Familial aggregation of hypertension was determined in 187 Japanese nuclear families. The necessary data on family and case history particularly concerning the hypertensive status were obtained by personal interviews of outpatients at six local hospitals, using a specifically designed questionnaire. 2. From the family history of the 187 living index children (single ascertainment), 134 pairs of parents were informative. Of 819 children, excluding index cases, the number of hypertensives, normotensives and status unknown were 224, 274 and 187, respectively. Individuals under 30 were classified as unknown. 3. For a child given the birth order, empirical risk to be hypertensive was calculated from the proportion of hypertensives to normotensives plus hypertensives. 4. Irrespective of parental mating types, among a simplex family of hypertension the index cases of the first-born child were more than the others. 5. There was no birth order effect in risk among multiplex families of hypertension. 6. There was no increase of hypertensive offsprings observed when the mother was hypertensive. PMID- 1446415 TI - The immune system in health and disease. AB - For an immune response against an eliciting antigen, innate and adaptive immune mechanisms interact to provide a specific and appropriate response characterized by self-non-self discrimination and memory. This non-random process involves antigen presentation followed by T cell recognition and activation with the elaboration of T cell-derived lymphokines. The nature and amount of lymphokine production from antigen-activated T cells then determines the predominant immune response (e.g. cytotoxicity versus antibody). Exogenous regulatory factors, including steroid hormones, prostaglandins, and cytokines, modulate immune responsiveness. How these regulatory factors influence the immune response during specific host-parasite interactions determines the predominant immune response to specific antigen. As the regulation of the immune response is unravelled, new and powerful immunomodulatory therapies will be developed and utilized to improve the immune response and host survival. PMID- 1446416 TI - The normal fetomaternal immune relationship. AB - The antigenic status of the preimplantation embryo is ill-defined and there are no clearly recognized maternal immune reactions against this early stage of development. Following implantation, the pregnant female shows evidence of immune recognition of her intrauterine allogeneic conceptus. In a proportion of pregnancies, particularly in multiparous women, there are maternal cytotoxic antibodies exhibiting specificity for the paternally inherited HLA antigens of the fetus. When these are undetectable there may be other antibodies that are non complement fixing and non-cytotoxic or antibodies that are not present as free molecules and incapable of identification in conventional assays. Anti-HLA antibodies pose no threat to the fetus, principally owing to their absorption by the placenta and, very likely, the harmless binding of any that do reach the fetal circulation. No potentially deleterious cytotoxic T lymphocyte generation occurs in most pregnancies. The extent to which this is due to maternal immunoregulatory control processes is not yet established. The fetal trophoblast is able to act as a protective barrier by virtue of unique properties, including a lack of conventional class I and class II HLA molecules, that render it insusceptible to immune attack. The nature and significance of any maternal recognition of non-HLA antigens on trophoblast await elucidation. Maternal immune cell traffic across the placenta occurs only at a very low level, if at all, in normal pregnancy. This may take place to a greater degree in some of the rare instances of fetal graft-versus-host disease, but this is complicated by the associated fetal immunodeficiency. Maternal IgG antibodies are transmitted across the placental trophoblast by receptor-dependent mechanisms to provide immediate protection for the neonate against environmental pathogens. Leakage of fetal erythrocytes, leukocytes and platelets into the maternal circulation can elicit IgG isoantibodies that take advantage of the same mechanisms to gain access to the fetus, with pathological consequences. Autoantibodies in women with various disease states may similarly pass into the fetus but these normally produce only mild and transient effects. The development of the fetal immune system begins at an early stage of gestation. It is competent to respond to intrauterine infections from as early as 12 weeks and has full functional potential at birth. Maternally acquired IgG is available for up to 9 months of life until the infant's own immune system has been adequately primed and activated following first exposure to specific antigens. The normal fetomaternal immune relationship represents a remarkable harmonious association between two genetically disparate individuals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446417 TI - Complement and pregnancy: new insights into the immunobiology of the fetomaternal relationship. AB - Recent studies have revealed that human trophoblast expresses three membrane bound proteins which function specifically to regulate the activity of complement. These proteins are already known to be widely distributed in normal adult tissues where they protect host cells from damage resulting from the fortuitous deposition of activated complement components. Their activities are focused at two distinct steps in the complement pathway. Decay accelerating factor (DAF, CD55) and membrane co-factor protein (MCP, CD46) act at the level of the C3 convertase enzymes which activate C3 to C3b. A further protein, CD59, directly regulates the formation and function of the terminal cytolytic membrane attack complex (MAC) by specifically interacting with C8 and C9. These proteins appear to play an important role in the maintenance of normal human pregnancy. DAF, MCP and CD59 are all expressed where trophoblast surfaces are in contact with maternal blood and tissues and expression occurs from at least 6 weeks of gestation. The semi-allogeneic human conceptus therefore appears to be effectively protected from maternal complement-mediated damage arising either from alternative or classical pathway activation or in a bystander fashion following a response to microbial infection in the mother. Complement regulatory protein deficiency disorders with clinically demonstrable consequences especially in terms of haemolytic disease are known to exist and have proved valuable in establishing the biological role of these proteins in vivo. The demonstration of this new family of immunoregulatory proteins on trophoblast raises important questions about the potential involvement of these products in pregnancy pathologies. PMID- 1446418 TI - Immunological contributions to recurrent pregnancy loss. PMID- 1446419 TI - Obstetrical implications of antiphospholipid antibodies. PMID- 1446420 TI - Alloimmune conditions and pregnancy. AB - Transfer of fetal red blood cells and platelets to the maternal circulation can stimulate an immune response with production of immunoglobulin that can cross the placenta. Similarly, passage of maternal stem cells to an immunologically incompetent fetus can theoretically produce graft-versus-host disease. disease. Maternal sensitization to red blood cell antigens such as D and Kell can result in anaemia, hydrops, and death in an incompatible fetus. Current assessment of these pregnancies involves serial analysis of amniotic fluid bilirubin concentration, with umbilical cord blood sampling reserved for special circumstances; neither ultrasound or Doppler blood flow analysis are accurate in the prediction of fetal haematocrit. Intravascular transfusion is the treatment of choice for hydropic fetuses. Perinatal survival in non-hydropic fetuses is similar with either intravascular or intraperitoneal transfusion, and the choice of procedures is individualized. Isoimmune fetal thrombocytopenia is usually the result of maternal sensitization to the PlA1 antigen. There is significant risk of intracranial haemorrhage, both antepartum and during labour and delivery. Umbilical cord blood sampling at term can determine fetal platelet count and the need for platelet transfusion, and can aid in deciding the appropriate route of delivery. PMID- 1446421 TI - Autoimmune disease in pregnancy. PMID- 1446422 TI - Immunological aspects of pre-eclampsia. AB - The first pregnancy preponderance and apparent partner specificity of pre eclampsia suggest that it might have an immune aetiology. The pathogenesis of pre eclampsia is undefined although it is clear that it is a placental disorder. The maternal syndrome appears to be mediated by placental ischaemia secondary to spiral artery insufficiency. This leads to a hypothesis that pre-eclampsia is a two-stage disease. The first comprises processes that limit the size of the spiral arteries (poor placentation) or obstruct them (acute atherosis). Either or both may have immunological causes although there is no direct evidence. Factors limiting placentation could involve maternal immune intolerance of the fetal allograft, which in their most extreme expression could lead to immunologically mediated abortion. Thus pre-eclampsia may be part of a wider spectrum of pregnancy loss secondary to poor maternal immune accommodation of her genetically disparate fetus. The second stage involves the consequences of the ensuing placental ischaemia. The syndrome is currently tentatively ascribed to diffuse maternal endothelial dysfunction. There is less reason to invoke immunological mechanisms in the second stage although neutrophil activation could explain generalized endothelial damage. It should be clear that these conclusions are provisional and that the greatest need is for more investigation to eliminate the uncertainty which clouds our concepts. PMID- 1446423 TI - HIV infection in women. PMID- 1446424 TI - Contraception. AB - The principle of vaccination for the purposes of fertility regulation is scientifically elegant and socially compelling. Factors such as economic production, convenience of use, relatively long-lasting but reversible protection, low failure rate and the avoidance of mechanical devices or exogenous hormones make this approach a potentially attractive option for family planning programmes in both developing and developed countries. The major efforts in research and development have involved the prospect of active immunization against specific antigens of sperm, oocyte, zygote and early embryo, and the pregnancy hormone human chorionic gonadotrophin (hCG). Several anti-hCG vaccines have entered clinical trials. They operate by preventing or interrupting pregnancy at the peri-implantation stage probably by neutralizing the luteotrophic effect of hCG. The most refined vaccine is one directed against the unique C-terminal peptide on the beta-subunit of hCG. This vaccine provokes antibodies that are specific for hCG and do not cross-react with human luteinizing hormone (hLH). Preclinical studies in baboons and data from a phase I human trial indicate that this method is free of side-effects and provides the promise of a duration of effectiveness of up to 12 months. Future research will optimize the anti-hCG approach, utilize new vaccine delivery systems and broaden the spectrum of target antigens of potential utility for contraceptive vaccines. PMID- 1446425 TI - Overview and future perspectives. PMID- 1446426 TI - Hydroxylapatite-coated hip implants. Multicenter three-year clinical and roentgenographic results. AB - The application of a thin coating of hydroxylapatite to total hip implants has provided the opportunity to realize stable fixation of a press-fit prosthesis without a porous coating or an intervening fibrous tissue layer. This series consists of 436 total hip arthroplasties, of which 320 cases have a minimum two year follow-up period and 142 cases have a minimum three-year follow-up period. The femoral prosthesis used was a roughened titanium alloy with a 50-microns surface treatment of hydroxylapatite applied to the proximal one third. The acetabular components implanted included porous-coated implants (132), hydroxylapatite-coated acetabular shells of varying geometries (285), and bipolar implants (16). Analysis of the clinical results demonstrates a mean Harris Hip Score of 93 at six-months postarthroplasty, 95 at one and two years, and 96 at three years. At the three-year follow-up evaluation, 4.2% of patients complained of mild to moderate pain in the operative limb, whereas only 2.2% at two years and 1.4% at three years complained of activity-related thigh pain. The femoral mechanical loosening rate representing stems revised for aseptic loosening (two) plus roentgenographically unstable stems (zero) is 0.46%. Three hydroxylapatite coated acetabular cups (1%) have shown measurable migration at two years, but none have been revised for aseptic loosening. The roentgenographic evaluation provides evidence for excellent proximal femoral fixation with distal stress transfer. Radiolucencies typically occur around the uncoated distal tip of the femoral stem (74%), but rarely in the proximal hydroxylapatite-coated anterior (3%) and lateral (2%) zones. Femoral cancellous condensation characteristically is seen at the transition zone of hydroxylapatite coated-to-uncoated stems (86%), whereas up to 32% of cases show cortical hypertrophy at the medial distal stem. These roentgenographic changes are progressive from one through three years postoperatively. PMID- 1446427 TI - Acrylic fragmentation in total hip replacements and its biological consequences. AB - Loosening of total joint prostheses is in part related to the fragmentation of the acrylic cement mantle surrounding the prosthesis and the biologic consequences to the particulate acrylic. Fractographic studies of femoral cement mantles retrieved at revision surgery and autopsy showed frequent fractures in varying stages of development in the cement and wear at the fracture surfaces. Defects in the cement mantle, thin mantles, sharp corners on the prosthesis, separation at the cement mantle interface, and pores in the cement were frequently associated with cement fractures. The progressive fractures and wear led to the liberation of particulate acrylic debris into the surrounding tissues. The tissues at the bone-cement interface removed at revision surgery showed that a macrophage, giant-cell foreign-body granulomatous reaction occurs in response to the particulate, but not bulk cement. This tissue can produce a variety of chemical mediators of inflammation and bone resorption, and can resorb bone in organ cultures. A granulomatous tissue reaction with a very similar appearance can be produced in experimental animals using particulate-form polymethylmethacrylate (PMMA), but not the bulk form of PMMA. The tissue reaction is not mediated by the classic cell or humeral immune mechanisms. Subcutaneous injection of particulate PMMA powder into fully immunocompetent C3Hf/SED mice as well as three strains of mice with progressive immunologic deficiencies (nude/nude, SCID, and triple deficient Nu-bg-XID/SED mice) led to a foreign-body reaction in all strains at five weeks as shown by histologic and immunohistochemical examination despite the differences in immune deficiency. This, along with the scarcity of lymphocytes in the human tissues, suggests that the biologic reactions to fragmented cement can be produced and sustained by nonimmune phagocytosis and activation by macrophages and giant cells without significant contribution by the immune system. PMID- 1446428 TI - Mechanisms of failure of modular prostheses. AB - The expectations of wear and longevity of total hip components are based in large part on Charnley's early work. The evolution of the total hip from the one-piece, all-polyethylene acetabular component and fixed-head femoral component to the myriad of parts that comprise many of today's total hip designs has brought with it an array of potential mechanisms for failure that were not present in the earlier design. The risk/benefit ratio of these new designs may need to be reevaluated based on the additional mechanisms for failure that they provide. One hundred eleven acetabular hip prostheses and 139 femoral prostheses, all of modular configuration, retrieved by surgeons in the field, and sent for histologic examination, were analyzed for this study. A number of component characteristics were found to be correlated to early failure. These included acetabular designs with thin polyethylene bearings, poor fixation of the polyethylene to the metal shell, and geometries that permitted a moment to be applied to the bearing insert, tending to cause it to rotate in the metal shell. Modular femoral components were observed to be susceptible to corrosion, with titanium-alloy stems mated to cast cobalt-alloy heads at greatest risk attributable to a galvanic effect. All modular connections of femoral and acetabular components are at risk for disassociation and fretting; therefore, clever design and precision machining are necessary to produce prostheses in which the benefits of modularity exceed the risks. PMID- 1446429 TI - Quantification of implant micromotion, strain shielding, and bone resorption with porous-coated anatomic medullary locking femoral prostheses. AB - Fourteen femora containing porous-coated anatomic medullary locking (AML) femoral prostheses were retrieved from 12 patients at autopsy. Clinical roentgenograms in 13 femora showed bone remodeling changes, indicating that the implants were fixed by osseointegration. Under simulated physiologic loading, micromotion between the implant and the bone was measured using electrical displacement transducers connected to the implant and to the adjacent cortex. The micromotion between the implants at the areas of porous coating and the adjacent cortex in the one case of failed bone ingrowth measured 150 microns. Maximum relative motion between the cortex and the implant in the areas of porous coating for the 13 cases showing signs of bone ingrowth was 40 microns, and this was completely elastic relative displacement. With all implants, the micromotion between the cortex and the stem was always greatest over the uncoated portion of the stem. Four of the implants were proximally porous coated. With these, the micromotion was greater over the uncoated areas than with more extensively coated stems and was always greatest at the uncoated tip of the prosthesis. The amount of micromotion was directly related to the extent of porous coating on the implant. Maximum tip motion for the proximally coated implants was 210 micra, whereas for the fully porous-coated implants, it was 40 microns. In nine of the autopsies, the contralateral normal femur was obtained in addition to the femur containing the AML (the in vivo remodeled femur). These were used for comparative studies of strain shielding and femoral remodeling. Cortical strains were measured in the in vivo remodeled femora and were compared with measurements made in the contralateral normal femora before and following implantation of a stem identical to that present on the clinically treated side. The data showed major strain reductions in all the postmortem implanted normal femora. Comparison of the strain data from the postmortem implanted normal femora with those from the in vivo remodeled femora clearly indicated that extensive bone remodeling did not result in restoration of cortical strain levels anywhere near normal. Strain shielding continued to exist in all of the remodeled specimens, even up to 7.5 years after surgery. This strain shielding was associated with bone remodeling changes that resulted in regional reductions in bone mineral content that ranged from 7% to 78%. These observations are unique, important, and valuable in defining the in vivo function and clinical behavior of this type of porous-coated femoral component. PMID- 1446430 TI - Debris from cobalt-chrome cable may cause acetabular loosening. AB - To address the issue of nonunion with trochanteric osteotomy, surgeons have experimented with various modes of fixation, wire and cable being the two most popular. From a group of 643 primary cemented total hip arthroplasties performed by a single surgeon via the trans-trochanteric approach, minimum four-year roentgenographic follow-up evaluations were performed on 322 hips (50%). The method of fixation was stainless steel monofilament wire in 162 cases and Co-Cr cable in 160. Trochanteric union rates were 75% (122 patients) for the wire group and 79% (126 patients) for the cable. Breakage rates of the entire trochanteric fixation construction (all three wires or cables) were 43% (68 patients) for the wire and 12% (20 patients) for the cable. Unraveled cable was seen in 56% of the hips (90 patients), and in 47% of these hips, there were no broken cables. Blinded roentgenographic analysis of the acetabulum, preformed independently, revealed that loosening of the acetabulum in the cable group was greater than in the wire group. Cables offer no significant benefit over wires and may have potential adverse effects. Generation of significant particulate debris was noted roentgenographically, and marked reaction/destruction was found at the time of revision surgery. PMID- 1446431 TI - Ultrasonic technology in revision joint arthroplasty. AB - The development of ultrasonically driven tools for revision joint arthroplasty is presented. The data represent seven-years' experience and include information from laboratory investigation and clinical experience from 20 surgical cases. Whole bone torsional strength studies reveal no decrease in strength parameters after the removal of cement ultrasonically. Comparison studies demonstrate that ultrasonic tools allow more rapid completion of cement and prosthesis removal than traditional manual tools. Histologic studies using an in vivo canine model demonstrate no deleterious effects to endosteal bone where cement had been removed by ultrasound. Clinical studies indicate that the use of ultrasound facilitates the surgery and causes no cortical perforations; the creation of cortical windows was not necessary in all cases. Ultrasound is safe and efficacious in cement and prosthesis removal during revision surgery. PMID- 1446432 TI - Modular femoral stem removal during total hip arthroplasty using a universal modular stem extractor. AB - Removal of a modular head femoral prosthesis may be extremely difficult during revision total hip arthroplasty (THA). A universal modular stem extractor was developed that achieves a secure attachment to the stem taper, and applies tensile forces with a five-pound slaphammer. Clinical use indicates that this new device facilitates uncomplicated modular femoral stem removal. PMID- 1446433 TI - Segmental cement extraction at revision total hip arthroplasty. AB - Cement removal in revision total hip arthroplasty can be technically challenging. Traditional methods involve using a combination of chisels, power burrs, and drills, as well as windowing the femoral cortex to gain access to cement distally. These methods can be associated with femoral fracture or uncontrolled cortical perforation and bone loss. A new technique had been developed that permits segmental extraction of bone cement from the femoral canal. Fresh cement is introduced into the old cement mantle and a threaded rod is placed into the wet cement and held in place while the cement hardens. The thread-forming rod is then removed leaving a threaded channel in the cement. Extraction rods are then screwed 1.5 to 2.5 cm into the threaded channel. A slap hammer, which attaches to the opposite end of the extraction rod, is used to remove 1.5- to 2.5-cm segments of cement. Fifteen cases involving revision of cemented femoral components were analyzed using this system. Complete cement removal was achieved in 12 cases with much less damage to the femur when compared with conventional methods. In two cases, there was retained cement along the medial wall of the femur and, in one case, the plug could not be extracted using this system. There were no fractures or cortical perforations in this series. PMID- 1446434 TI - The removal of porous-coated femoral hip stems. AB - During a ten-year period, 70 porous-coated femoral hip components of several designs were removed for various reasons. Based on this experience, techniques for the removal of porous-coated stems have evolved and are described, including a newer method for the safe removal of extensively coated bone-ingrown stems. Preoperative roentgenograms were highly predictive of fixation mode as corroborated by intraoperative mechanical testing, gross inspection, and histologic examination. Stable implants (17 bone-ingrown and 11 fibrous tissue encapsulated) required interface access and division before their removal. Minimal bone damage was incurred, and in no case was reconstruction precluded by stem removal. There were no unplanned cortical perforations. Two minor femoral fractures occurred. The authors present an overall approach and specific surgical techniques that facilitate the safe removal of porous-coated femoral stems on a consistent basis. PMID- 1446435 TI - Articular geometry of the glenohumeral joint. AB - Little quantitative data exists defining the true shape of the humeral head and glenoid articular surfaces. This study uses a precise stereophotogrammetry (SPG) technique and provides highly accurate quantitative results for determining the three-dimensional geometry of glenohumeral joint articular surfaces, including their "sphericity", surface areas, cartilage thickness, and the difference in these quantities between the genders. Results indicate that glenohumeral joint surfaces may be approximated by a section of a sphere with small deviations from sphericity of less than 1% of the radius. Furthermore, results indicate that mating humeral head and glenoid articular surfaces are quite congruent and have radii within 2 mm in 88% of cases, and within 3 mm in all cases measured. The lack of anatomic stability of this joint is therefore not attributable to the relative shallowness or lack of congruence of the joint but rather to the small surface area of the glenoid which does not enclose the humeral head. Cartilage thickness results may partially explain perceptions of glenohumeral incongruity obtained from roentgenographic measurements where the glenoid appears flatter than the corresponding humeral head. Only when the actual articular cartilage surfaces are analyzed is it determined that the actual articulating surfaces do conform. PMID- 1446436 TI - Scapulothoracic motion in normal shoulders and shoulders with glenohumeral instability and impingement syndrome. A study using Moire topographic analysis. AB - Qualitative visual inspection and manual muscle testing are traditional methods of evaluation that may overlook subtle weakness of the axioscapular musculature. A modification of the standard technique of Moire topographic analysis of spinal deformity was applied to assess axioscapular muscle function in 51 subjects: 22 asymptomatic individuals, 22 with shoulder instability, and seven with impingement syndrome. Static Moire evaluation demonstrated scapulothoracic asymmetry or increased topography in 14% of asymptomatic subjects, compared with 32% and 57% in the instability and impingement groups, respectively. The dynamic Moire test demonstrated an abnormal Moire pattern in 18% of asymptomatic individuals, compared with 64% and 100% in the instability and impingement groups, respectively. Axioscapular muscle dysfunction is common with both instability and impingement syndrome of the shoulder, although it remains to be determined whether this represents a primary or secondary phenomenon. PMID- 1446437 TI - Hand and wrist function after external fixation of unstable distal radial fractures. AB - Twenty-eight patients with 31 fractures of the distal radius were treated by closed external fixation. The complication rate for this series was 50%. Anatomic results were acceptable but hand function at final review was disappointing, particularly in the measurement of grip strength and the patient's ability to perform the activities of daily living. There was a highly significant correlation between complications and poor functional outcome. Although external fixation can achieve restoration of normal anatomy, functional outcome may be poor because of the severity of the associated soft tissue injury. PMID- 1446438 TI - Congenital trigger digit. AB - Release of the sheath of the flexor tendon is the accepted solution for the problem of congenital trigger digits in children. A series of 27 patients with 37 trigger digits were observed over a period of 18 years: the average follow-up on these patients was 46.9 months. Thirty-two thumbs, three long fingers, and two ring fingers showed locking and a degree of triggering. Thirty-three digits required surgery. The surgical treatment is simple and effective. The outcome in most cases shows that this is a conservative approach. PMID- 1446439 TI - Carpal canal stenosis in men with idiopathic carpal tunnel syndrome. AB - The carpal canal and carpal bones of 14 male patients with idiopathic carpal tunnel syndrome and 26 normal male controls were examined by computed tomography. When compared with the controls, there was significant stenosis of the proximal part but not of the distal part of the carpal canal. Carpal canal stenosis is an important etiologic factor in the development of idiopathic carpal tunnel syndrome in males. PMID- 1446440 TI - Bilateral diskoid medial menisci diagnosed by magnetic resonance imaging: a case report. AB - A diskoid medial meniscus is a rare finding occurring in approximately 0.3% of the general population. Bilateral medial diskoid menisci are even less common, with only three other cases appearing in the literature. This may be the first reported case of bilateral medial diskoid menisci diagnosed by magnetic resonance imaging and verified at arthroscopy. PMID- 1446441 TI - Knee extensor mechanics after subtotal excision of the patella. AB - Two sets of six fresh frozen autopsy specimens were used to test the quadriceps force requirements for knee extension after sequential distal-to-proximal and proximal-to-distal excisions of the patella. The quadriceps force as a function of knee flexion angle was recorded for varying amounts of excision and compared with the results for total patellectomy. Excision of the proximal one half or less resulted in lower force requirements when compared with total patellectomy. The effects of removal of the proximal three-fourths length of patella were inconsistent and actually increased the force requirements in three knees. The effects of distal to proximal excisions indicate a biomechanical advantage to maintaining a fragment equal to at least three fourths the length of the proximal patella. Retaining a fragment of adequate size preserves at least some of the mechanical advantage provided by the intact patella. PMID- 1446442 TI - Fractures of the femur treated by intramedullary nailing using the fluted rod. A report of 193 consecutive cases. AB - One hundred ninety-three of 196 acute nonpathologic femoral shaft fractures were treated consecutively with intramedullary nailing using the fluted rod. Closed intramedullary nailing was used in 126 fractures, and an open technique was used in 67. This series includes 58 open fractures and 104 comminuted fractures. All fractures treated with the fluted rod united. Complications included three superficial infections (1.5%). Malrotation greater than 20 degrees was noted in six patients (3.1%). Significant shortening (5 cm), which required treatment, occurred in one patient. After initial resuscitation and evaluation, routine treatment included preoperative traction and a first-generation cephalosporin followed by accurate reduction and nailing of the fracture. The results of this series suggest that the fluted rod may be ideal for the treatment of most femoral shaft fractures. PMID- 1446444 TI - Intramedullary nailing of tibial nonunions. AB - Fifteen tibial nonunions, ranging nine months to 19 years after original injury, were treated with the Brooker intramedullary nail (IMN). The average number of previous failed surgeries was two. The fracture location ranged from several centimeters below the tubercle to 3 cm above the plafond. Twelve of 15 had bone grafting, and all 15 had fibular osteotomy at the time of the IMN procedure. Thirteen of 15 were reamed, and 11 of 15 were nailed open. Patients required an average of five postoperative days in the hospital, and 14 of 15 tibial nonunions healed uneventfully at an average of eight months after the IMN procedure. Weight bearing in a removable patellar-tendon-bearing (PTB) brace was encouraged in most cases by two to four weeks postoperative. One nonunion patent, traumatically refractured after rod removal, was treated at another hospital with dynamic compression plating and iliac crest bone graft; the fracture healed three months later but was considered an IMN treatment failure. There were no other significant complications. The IMN procedure encourages early return to function and reliably promotes union in even the most challenging and complex of tibial healing problems. PMID- 1446443 TI - Olecranon fractures. A clinical and radiographic comparison of tension band wiring and plate fixation. AB - Forty-one adult patients with displaced olecranon fractures were treated with open reduction internal fixation in a prospective, randomized study comparing tension band wiring (TBW) and plate fixation (PF). Plate fixation required longer operative time, but did not lead to an increased complication rate. Range of elbow motion at six months did not differ significantly between the two groups. Symptomatic metal prominence was frequently observed after TBW (42%), although true Kirschner wire (K-wire) migration was seen in only one patient. Postoperative loss of reduction, leading to a significant articular step-off or gap, was more frequent after TBW (53%) than after PF (5%). Tension band wiring resulted in 37% good clinical and 47% good roentgenographic results, as compared with PF, which resulted in 63% good clinical and 86% good roentgenographic results. Plate fixation should be carefully considered when planning open reduction and internal fixation of displaced olecranon fractures. PMID- 1446445 TI - Experimentally produced ankle fractures in autopsy specimens. AB - Twenty-six unembalmed lower-leg specimens were mounted in an experimental test device with the foot placed at a fixed degree of pronation/supination, dorsiflexion/plantar flexion, or both. Torque versus rotation curves were determined as each foot was externally rotated to failure. Torsional stiffness was determined for the first 20 degrees of external rotation, and energy to failure was noted at the point of initial failure. Anatomic dissection and roentgenographs delineated the degree of injury in all specimens. Gender had the greatest effect on both torque and energy parameters, and the injury pattern. In males, 67% of specimens had an oblique fibular fracture, torn anterior tibiofibular ligament, and torn deltoid ligament (SER2). In females, 45% had a transverse fibular fracture without syndesmotic or deltoid injury. Forty percent of females had the SER2 injury. Angle of supination/pronation did not correlate with a specific injury pattern. Peak axial load had a significant effect on stiffness, but increasing the load by more than three times body weight did not increase injury severity. PMID- 1446446 TI - The articular manifestations of Paget's disease of bone. A case report. AB - Disorders of joints are commonly associated with Paget's disease of bone but are often disregarded or attributed to the underlying Pagetic condition. The authors evaluated a 69-year-old man with extensive Paget's disease of bone, degenerative arthritis, calcific periarthritis, and gout. The degenerative arthritis and calcific periarthritis of the shoulders was originally mistaken for Paget's disease of the proximal humerus. The wrist arthritis was attributed to Paget's disease until evaluation of surgical pathology specimens showed intraarticular gouty granulomas. In evaluating and treating a patient with Paget's disease of bone, the orthopedic surgeon should be aware that the successful treatment of associated articular disorders may require therapeutic measures in addition to those used in treating the Paget's disease. PMID- 1446447 TI - In vitro bone-cell response to a capacitively coupled electrical field. The role of field strength, pulse pattern, and duty cycle. AB - Newborn rat calvarial bone cells were grown to confluence and subjected to a matrix of sine wave 60-kHz capacitively coupled electrical signals of various field strengths, pulse-burst patterns, and duty cycles. Both [3H] thymidine incorporation into DNA and alkaline phosphatase activity were evaluated in field strengths ranging from 0.0001 to 20 mV/cm, with pulse-burst patterns ranging from continuous to 5 milliseconds ON/495 milliseconds OFF, with daily duty cycles ranging from 0.25% to 25%. A significant increase in proliferation occurred in field strengths of 0.1, 1, and 20 mV/cm when the signal was applied continuously for six hours. Significant proliferation also occurred when the 20-mV/cm field was pulsed for six hours at 5 milliseconds ON/495 milliseconds OFF and at 5 milliseconds ON/245 milliseconds OFF. No change in alkaline phosphatase activity occurred in the 20-mV/cm field with any signal. At 1 mV/cm, there was a significant decrease in alkaline phosphatase activity in the continuous signal and in the 5 milliseconds ON/62 milliseconds OFF signal; in the lower fields evaluated, there was an actual decrease in alkaline phosphatase activity with some of the signals. The field strength plays a dominant role in determining the bone-cell's proliferative response, and to a lesser extent the alkaline phosphatase activity response, to a capacitively coupled electric field. The pulse configuration and the duty cycle are also important, but only if the proper field strength is being applied to the cell. PMID- 1446448 TI - Changes in somatosensory-evoked potentials in limb lengthening. An experimental study on rabbits' tibiae. AB - To assess the influence of the rate and amount of distraction on the electrophysiologic function of the peripheral nerve during limb lengthening, somatosensory-evoked potential (SSEP) studies were performed on the hindlimbs of 96 rabbits. In Group I, the tibiae were lengthened 0.35 mm per day; in Group II, 0.7 mm per day; in Group III, 1.05 mm per day; and in Group IV, 1.4 mm per day. The studies were done preoperatively and then postoperatively, until six weeks in Group I, five weeks in Group II, four weeks in Group III, and three weeks in Group IV. As lengthening proceeded, the P1 (the first major positive peak) latency gradually increased, whereas the amplitude decreased. Significant amplitude changes were observed at six-weeks postsurgery in Group I, three weeks in Group II, two weeks in Group III, and one week in Group IV. Significant changes in P1 latency were observed at four weeks postsurgery in Group II, three weeks in Group III, and two weeks in Group IV. Greater percentage increases in tibial length corresponded to more marked changes in P1 latency and amplitude. The SSEP monitoring may serve as an effective tool for early detection of neurologic dysfunction during limb lengthening. PMID- 1446449 TI - Positive correlation between ulnar shortness (relative to the radius) and Kienbock's disease. PMID- 1446450 TI - A comparison of magnetic resonance imaging to bone scintigraphy in early traumatic ischemia of the femoral head. AB - In adult rabbits, a unilateral subcapital osteotomy of the femoral neck was performed to induce avascularity. One half of the osteotomy sites were fixed with a magnetic resonance imaging (MRI) compatible absorbable pin and the other osteotomies had no fixation. The femoral heads were studied at three, five, and 12 days with roentgenographs, bone scintigraphy, and MRI, and MRI only at four weeks and six weeks after osteotomy. Histologic studies were performed after imaging to evaluate the viability of the femoral heads. At three, five, and 12 days after osteotomy, bone scintigraphy showed a decrease in uptake of radioisotope in the region of the femoral head on the operated side relative to the acetabulum and greater trochanter in 17 of 18 rabbits. A comparison of the surgically treated hip to the normal hip in fixed and unfixed osteotomies showed no change in the signal behavior of T1- or T2-weighted images in all rabbits Days 3, 5, and 12 (n = 18) after operation. The rabbit femoral heads with fixation of the osteotomy 28 days after operation showed a decrease in signal intensity in the subcapital region of the femoral head. Six weeks after operation, the fixed femoral head shows a loss of signal in a portion of the femoral head near the osteotomy. The MRI signal intensity appears to increase in the unfixed femoral heads six weeks after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446451 TI - Cortical strut allografts in the reconstruction of the femur in revision total hip arthroplasty. A basic science and clinical study. AB - Repeated total hip arthroplasties cause a loss of bone stock that will produce diminished component support, and can compromise implant function. There is, therefore, a compelling argument to return bone stock to the femur at the time of revision arthroplasty. Cortical strut allografts serve this purpose. They unite consistently and reliably, by 8.4 months on average. The overall rate of strut union is 96.6%. The sequence of healing events starts with round-off, followed by partial bridging and complete bridging. The repair process includes remodeling of the host femur, as well as the graft. Although there is variable resorption of some grafts, usually where not opposed to the host bone, there is also extension of others from host callus build-up such that, on average, there is no significant measurable loss of graft length or width. Most of the allograft struts, 78%, maintained a radiodense appearance. Clinical results of femoral revision with strut allografting have shown satisfactory end results compared with historic controls, with an average Harris score of 79.6 and a 2.7% subsidence rate. Of particular note is that the subsidence rate and clinical scores did not vary with the state of the preoperative femur, as has been shown repeatedly in the past. The canine model shows that the strut allografts are biologically active. Through mobilization of mesenchymal tissue, they are transformed into vascularized calluslike structures while maintaining good strength, and then further remodel to lamellar bone. PMID- 1446452 TI - Metal to metal total hip joint replacement using the Urist socket. An end result study. 1973. PMID- 1446453 TI - Charnley low-friction arthroplasty in the young patient. AB - One thousand three hundred forty-two Charnley low-friction arthroplasties (LFAs) were reviewed at an average of ten years four months after surgery. Patients' average age at surgery was 41 years. The clinical results at follow-up review remained excellent: 79% were pain free and 11% had no more than occasional discomfort. One hundred forty-one (10.5%) LFAs have been revised so far. Stem fracture has been completely eliminated. Revision for stem loosening has been reduced to below 1% and revision for socket loosening has also been reduced. The long-term problem remains socket wear--and with it--an increasing incidence of socket migration. Failure of component fixation is a short- and medium-term problem that has been improved by better component design and surgical technique. PMID- 1446454 TI - A knowledge-based computer-aided design and manufacturing system for total hip replacement. AB - A knowledge-based computer-aided design and manufacturing system (CAD-CAM) has been developed for total hip replacement. Knowledge-based refers to the fact that the design process is a computer program that has been provided with preprogrammed design rules. Compared with conventional CAD-CAM systems, the knowledge-based system is automated, requires less designer intervention, and increases the accuracy of the design process. The capabilities of the system make it ideal for the design of standard and custom total hip replacement. A full fill, press-fit custom total hip replacement has been designed using the knowledge-based system. The early clinical results of a series of 37 replacements in 31 patients is described in this paper. PMID- 1446455 TI - Development of a surgical robot for cementless total hip arthroplasty. AB - The long-term success of cementless total hip arthroplasty (THA) may depend on bone ingrowth into the porous-fixation surfaces of the implant. The ingrowth process is facilitated when the surgeon achieves a satisfactory fit for the prosthesis. Clinically or roentgenographically visible failure and persistent thigh pain after cementless THA remain significant problems, both of which may be alleviated by more precise preparation of the femoral canal and selection of an appropriately sized prosthesis. The objective of this study was to obtain an exact fit for the prosthesis through the use of an image-directed surgical robot for femoral canal preparation. PMID- 1446456 TI - Is it advantageous to strengthen the cement-metal interface and use a collar for cemented femoral components of total hip replacements? AB - The mechanism of initiation of loosening of cemented femoral components is now known. It is debonding at the cement-metal interface. Current data strongly support the concept that a collar and improvement of the cement-metal interface are valuable. Precoating and having a roughened surface proximally and distally on the stem contribute to extended longevity of the cement-metal interface. Using contemporary instrumentation, collar-calcar contact can be achieved regularly and, once achieved, is well maintained for years. PMID- 1446457 TI - The silver anniversary of The Hip Society. A brief history. PMID- 1446458 TI - The use of a collar and precoating on cemented femoral stems is unnecessary and detrimental. AB - Evidence is presented, largely from clinical sources, that a large collar is not necessary for the transfer of load to the proximal femur in cemented total hip arthroplasty. In fact, the use of a collar may have a number of deleterious side effects that cannot be predicted from theoretical analyses. Concern is also raised over the use of precoated femoral stems. PMID- 1446459 TI - Do we need to vacuum mix or centrifuge cement? AB - In total hip surgery, the goal of porosity reduction techniques in the preparation of acrylic bone cement is to provide a stronger, more fatigue resistant material between the implant and bone. Conventional mixing of polymethylmethacrylate bone cement produces porosity of 5% to 16%, whereas vacuum mixing or centrifugation reduces the porosity to a range of 0.1% to 3.4%. Multiple studies have demonstrated that this results in a cement that has a significant increase in static and dynamic testing to failure. Fracture of the cement mantle has been found as a part of the failure pattern in many total hip prostheses requiring revision for loosening. Vacuum mixing or centrifugation produces a stronger cement to resist the component of loosening caused by fracture of the cement mantle. Where failure occurs at the bone-cement interface, as in cemented acetabular migration, no improvements from porosity reduction would be expected. Along with enhanced femoral designs, improvements in cement technique with modern methods of bone preparation and administration of the cement have resulted in a marked improvement in clinical and roentgenographic loosening rates in cemented femoral components at medium-term follow-up periods of five to ten years. Intact total hip prostheses, retrieved for reasons other than loosening, at longer-term follow-up periods, have shown intact bone-cement interfaces. However, these specimens have also shown incipient cracks in the acrylic cement that emanate from and connect defects in the cement mantle and at the metal-cement interface. The use of a void-free, structurally stronger material is expected to improve the stability and longevity of the cement supporting femoral implants. PMID- 1446460 TI - Roentgenographic and mechanical performance of centrifuged cement in a simulated total hip arthroplasty model. AB - Roentgenographic analysis showed that centrifugation significantly reduced the gross and regional porosity of the cement compared with hand-mixed controls in a simulated total hip arthroplasty model. Static failure test of the prosthetic system demonstrated that the centrifuged cement had significantly greater strength than the hand-mixed cement. Under low-cycle fatigue tests of the same composite models, there was a trend for the centrifuged cement to be stronger than the hand-mixed specimens, although statistically it was not significant. Thus, centrifugation can reduce porosity and significantly improve the static strength of cement in a simulated in vitro total hip replacement model. When cement is used, any possible improvement in the physical properties of bone cement should be considered. PMID- 1446461 TI - Drug therapy of hyperlipidemia. PMID- 1446462 TI - Bronchoalveolar lavage. Let's focus on clinical utility. PMID- 1446463 TI - Weaning parameters. Are they clinically useful? PMID- 1446464 TI - Department of minimally invasive medical and surgical techniques. PMID- 1446465 TI - Perivascular fibrosis of muscular pulmonary arteries in chronic obstructive pulmonary disease. AB - We performed a morphometric analysis of peribronchiolar and perivascular fibrosis in lungs obtained at autopsy from six patients with chronic bronchitis, six with pulmonary emphysema, and four normal control subjects. The areas of fibrosis outside the smooth muscle layer of bronchioles and outside the external elastic lamina of muscular pulmonary arteries were measured and their thickness was then calculated by assuming a round airway or artery. Patients with chronic bronchitis had significantly thicker peribronchiolar fibrosis in bronchioles of 1 mm or less in diameter and also thicker perivascular fibrosis of the adjacent muscular pulmonary arteries than the other two groups. The extent of perivascular fibrosis was significantly correlated with peribronchiolar fibrosis only in the muscular pulmonary arteries adjacent to the bronchioles but not in those away from the bronchioles. These findings suggest direct extension of chronic inflammation from bronchioles to the adjacent muscular pulmonary arteries in chronic bronchitis but not in pulmonary emphysema. Such perivascular fibrosis might lead to sustained pulmonary hypertension. PMID- 1446466 TI - Nasal CPAP continues to improve sleep-disordered breathing and daytime oxygenation over long-term follow-up of occlusive sleep apnea syndrome. AB - To assess the effects of long-term nasal continuous positive airway pressure (CPAP) in occlusive sleep apnea syndrome (OSA), 17 patients with severe symptomatic OSA had repeated spirometry, arterial blood gases, and nocturnal polysomnograms off nasal CPAP after 3 to 46 months of treatment with nasal CPAP. Without loss of weight or change in respiratory mechanics, the ventilatory disturbance index fell from a mean of 87 events per hour to 57 events per hour (p < 0.0001), correlating with an improvement in mean nocturnal desaturation with sleep-disordered breathing events (r = 0.54, p = 0.03). Moreover, the daytime PaO2 rose significantly from a mean of 69 mm Hg to a mean of 82 mm Hg (P = 0.0001) at follow-up. The rise in daytime PaO2 was not only due to the alleviation of daytime hypercapnea observed in eight of nine hypercapneic subjects since the P(A-a)O2 gradient also decreased significantly. The improvement in PaO2 correlated significantly with the number of months of CPAP therapy, suggesting a continuing effect over time (r = 0.58, p = 0.015). These results indicate that there is a reversible element of the severity of OSA and suggest a result of nasal CPAP therapy may be to reverse the adverse and time dependent effects of hypoxemia and sleep fragmentation on ventilatory control in severe OSA. PMID- 1446467 TI - Sleep-disordered breathing in patients with Duchenne muscular dystrophy using negative pressure ventilators. AB - We studied the occurrence of nocturnal disordered breathing events and O2 desaturations in 12 patients with late-stage Duchenne muscular dystrophy (DMD) using negative pressure ventilators. We also assessed the effects of O2 supplementation and nasal continuous positive airway pressure (CPAP) on disordered breathing events in selected patients and examined sleep quality in a small subgroup. Average age was 23 + 2 years and FVC was 293 + 33 ml. Eleven of the 12 patients had more than five disordered breathing events per hour during nocturnal monitoring, and the lowest O2 saturation was < 85 percent in nine patients. Nasal O2 (2 L/min) during negative pressure ventilation in four patients did not alter the frequency of disordered breathing events, prolonged the mean and maximum durations of events, and failed to eliminate severe O2 desaturations in two patients. Nasal CPAP was used in two patients during negative pressure ventilation and completely eliminated disordered breathing events in both. Overnight polysomnography during negative pressure ventilation in three patients demonstrated frequent awakenings that fell in frequency following elective tracheostomy in two patients and use of nasal CPAP in one. We conclude that negative pressure ventilation in patients with late-stage DMD is associated with frequent disordered breathing events and severe O2 desaturations in many patients. Concomitant use of O2 supplementation may prolong the events, but a switch to positive pressure ventilation or addition of nasal CPAP is effective therapy. PMID- 1446468 TI - The relationship between sleep apnea syndrome and hypothyroidism. AB - To evaluate the prevalence of obstructive sleep apnea syndrome (OSAS) in patients with hypothyroidism, the prevalence of hypothyroidism in patients with OSAS, the possible factors predisposing to sleep-related breathing disorder in hypothyroid patients, and the effect of thyroid hormone in treating hypothyroidism associated with OSAS, we studied 65 patients with proven OSAS (apnea index [AI] > 5) and 20 hypothyroid patients. All patients were monitored for one overnight sleep study using polysomnography (Grass 78). We found only two (3.1 percent) of 65 OSAS patients had thyroid hypofunction. Of 20 patients with hypothyroidism, two showed moderate to severe OSAS and three had mild OSAS. Patients with both hypothyroidism and OSAS had impaired respiratory drive, but this was corrected by thyroid hormone therapy. Patients with hypothyroidism without OSAS were younger and had a lower percentage of ideal body weight than those with both hypothyroidism and OSAS. All hypothyroid patients were snorers. Thyroid hormone replacement was effective in correcting snoring only after one year of therapy. We conclude the following: (1) an overnight sleep study is not necessary in every case of hypothyroidism; (2) thyroid function studies need not be done routinely for every OSAS patient; (3) thyroid hormone therapy is effective for OSAS but it takes longer to correct the snore than respiratory drive; and (4) age and body weight are related to the development of OSAS. PMID- 1446469 TI - Chronic persistent cough and clearance of esophageal acid. AB - Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p < 0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p < 0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid. PMID- 1446470 TI - Pattern of non-ICU inpatient supplemental oxygen utilization in a university hospital. AB - Random assessments of SaO2 were performed via pulse oximetry in 274 hospitalized non-ICU patients prescribed supplemental O2 in a large tertiary care university hospital. In 507 assessments performed in patients inspiring the prescribed O2, 426 were receiving excessive amounts of O2 to maintain a SaO2 > or = 92 percent. In 233 of these assessments, SaO2 was > or = 92 percent while breathing ambient air. In an additional 193 assessments, the concentration of inspired supplemental O2 was excessive to maintain a SaO2 > or = 92 percent. However, in 81 assessments performed in patients inspiring O2, the prescribed amount was insufficient to maintain SaO2 > or = 92 percent. These results indicate that O2 prescription in hospitalized non-ICU patients is excessive or not required in the majority of cases. Furthermore, routine use of pulse oximetry in hospitalized patients prescribed O2 may be useful in determining the continued need for supplemental O2 and adjusting the proper concentration needed to avoid hypoxemia. PMID- 1446471 TI - Acute outcome of directional coronary atherectomy vs standard balloon angioplasty in de novo left anterior descending stenoses. AB - To assess the immediate outcome of directional coronary atherectomy (DCA) versus standard balloon angioplasty (PTCA) in de novo left anterior descending coronary stenoses, 25 consecutive atherectomies (22 men, 3 women) performed at The Toronto Hospital, between July 1990 and March 1991 were compared with 25 (14 men, 11 women) temporally matched successful angioplasties. Coronary stenoses were analyzed by quantitative arteriography, using the Coronary Measurement System (Leiden, The Netherlands), with estimation of transstenotic hemodynamics by fluid dynamic equations. Before and after procedure qualitative blood flow (TIMI criteria) was also evaluated, as was intimal haziness and coronary dissection. In comparison to PTCA, coronary atherectomy produced less residual minimum stenotic diameter (DCA, 2.75 +/- 0.55 vs PTCA, 1.70 +/- 0.44 mm, p < 0.001), and relative percent diameter stenosis (DCA, 17.9 +/- 10.7 vs PTCA, 34.4 +/- 10.7 percent, p < 0.001), with less transstenotic obstructive gradient (DCA, 0.2 +/- 0.2 vs PTCA, 1.0 +/- 1.5 mm Hg, p < 0.05), and greater estimated stenotic flow reserve (DCA, 4.86 +/- 0.15 vs PTCA, 4.50 +/- 0.48 x baseline, p < 0.05). Coronary atherectomy "normalized" TIMI flow patterns in virtually all patients (DCA, 2.96 +/- 0.20 vs PTCA, 2.72 +/- 0.45, p < 0.05), while creating less intimal haziness (DCA, 10/25 [40 percent] vs PTCA, 23/25 [92 percent], p < 0.01), and coronary dissection (DCA, 6/25 [24 percent] vs PTCA, 16/25 [64 percent], p < 0.05). Therefore, when compared with standard balloon angioplasty, DCA produces less residual stenosis, better transstenotic hemodynamics, while decreasing the frequency of coronary artery damage, in de novo left anterior descending stenoses. PMID- 1446472 TI - Creatine kinase and creatine kinase-MB isoenzyme during and after exercise testing in normal and obese young people. AB - We report creatine kinase (CK) and CK-MB values during a cycloergometric test up to maximal work capacity in 10 normal subjects aged 20 to 39 years (mean body mass index, 22 kg/m2) and 11 obese patients aged 17 to 42 years (mean body mass index, 41 kg/m2), all without any cardiorespiratory diseases. Total CK was significantly higher in obese patients. The CK-MB was not significantly different between the two groups, except at the first recovery when it was increased in obese patients and decreased in normal subjects. These results could be due to more important total stress of the total musculature, especially cardiac, and especially cardiac musculature in obese patients during a physical effort. Considering the mean values of total CK of our obese patients, it may be possible that they have myocardial damage at percentages of CK-MB less than those of lean subjects generally accepted at more than 4 percent. Moreover, in obese heart patients myocardial distress during exercise testing may be present despite heart rate at peak exercise beneath the theoretic maximal. PMID- 1446473 TI - Using contrast material-enhanced echocardiography to identify abnormal pulmonary arteriovenous connections in patients with hypoxemia. AB - The phenomenon of abnormal pulmonary arteriovenous connections in patients with acquired lung disease rarely has been reported. We report three patients with acquired lung disease and hypoxia that did not respond to the administration of 100 percent oxygen. Contrast-material-enhanced echocardiography demonstrated intrapulmonary right-to-left shunting in all three patients. These cases suggest that patients with hypoxia due to acquired lung disease may be screened by contrast-enhanced echocardiography to identify the presence and the location of anatomic right-to-left shunts. PMID- 1446474 TI - Postoperative atelectasis reexpansion by selective insufflation through a balloon tipped catheter. AB - Although treatment of refractory atelectasis has been improved by pulmonary insufflation through FOB with balloon cuff, low pulmonary compliance and high critical opening pressure of alveoli in the atelectatic areas require a more selective approach to prevent pressure dispersion to highly compliant zones. To achieve the highest insufflation selectivity and reduce patient discomfort, we have devised a small caliber balloon-tipped catheter to easily reach even the minor branches of the bronchial tree. This result was obtained by utilizing the performed curve of the catheter distal end after withdrawing the internal stylet. The catheter was introduced through the nostrils (16 patients) or through an endotracheal tube (two patients) and advanced under fluoroscopic guidance. Reexpansion of atelectatic areas was accomplished by repeated air injections through a 60-ml syringe. No complications were observed. Complete disappearance of x-ray film evidence of atelectasis was obtained in 15 patients and partial reexpansion in 3 patients. PMID- 1446475 TI - Can portable chest x-ray examination accurately diagnose lung consolidation after major abdominal surgery? A comparison with computed tomography scan. AB - PURPOSE: To prospectively quantify the degree of accuracy of portable chest x-ray film examination in the detection of postoperative lung consolidations. STUDY: Nineteen patients had a chest x-ray film and computed tomography (CT) scan the day before and 48 h following elective abdominal aortic replacement. RESULTS: The diagnosis of lung consolidations by x-ray film examination showed sensitivity of between 0.33 and 1.00, depending on the lung zone considered (lower at the lung bases). Specificity always was greater than 0.79. Radiologic lung volume decreased 16 percent postoperatively (p < 0.01) on average and noninflated parenchyma increased by a factor of 3 (p < 0.0001). Postoperatively, PaO2 correlated with the amount of condensed lung by CT scan (p < 0.002). CONCLUSION: In postoperative conditions, x-ray film examination is a method which presents good specificity but poor sensitivity in the diagnosis of lung consolidations. PMID- 1446476 TI - Lung cancer in patients with human immunodeficiency virus infection compared with historic control subjects. AB - Lung cancer infrequently may be associated with human immunodeficiency virus (HIV) infection. This retrospective case-control study was undertaken to determine if there were differences in age, sex, and stage distribution and in survival between HIV-positive and HIV-indeterminate lung cancer patients. We compared 19 patients with both pathologically verified lung cancer and HIV infection proved by serologic study with lung cancer patients with an indeterminate HIV status. All 19 HIV-positive lung cancer patients were men. This was significantly (p = 0.004) different from the 69 percent male preponderance in 1,335 HIV-indeterminate lung cancer patients. Median ages of HIV-positive and HIV indeterminate patients were 48 and 61 years, respectively. HIV-positive patients were significantly (p = 0.0139) younger. Stage distribution was similar in both groups. Histologic features and smoking were not significantly different between the two groups. Survival data that were available in 16 HIV-positive patients were compared with 32 HIV-indeterminate control subjects matched for stage, age, sex, and race. The median survival was three months in the HIV-positive group and ten months in the HIV-indeterminate cohort. The survival was significantly different (p = 0.002). There were no one-year survivors in HIV-positive lung cancer patients. PMID- 1446477 TI - Increased inhaled bronchodilator vs increased inhaled corticosteroid in the control of moderate asthma. AB - Undertreatment of chronic asthma may reflect uncertainty as to how it may be best controlled. We compared the effects of increased inhaled corticosteroid vs regular inhaled bronchodilator in 32 adult asthmatics. During three 16-week treatment periods, comprising baseline inhaled corticosteroid (mean 505 micrograms daily) and on-demand beta-agonist, baseline inhaled corticosteroid and increased (regularly scheduled four times daily) beta-agonist, and increased inhaled corticosteroid (mean 1478 micrograms daily) and on-demand beta-agonist, subjects recorded symptoms, morning and evening peak flow, and additional medication. Of 25 subjects whose control differed significantly between treatments with baseline vs increased corticosteroid, 22 (88 percent) favored the increased dosage (p < 0.001). Of 28 subjects whose control differed between treatments with regular beta-agonist vs increased corticosteroid, 24 (86 percent) were better controlled with increased inhaled corticosteroid and were worse with regular beta-agonist (p < 0.001). Only one quarter the number of exacerbations were experienced during treatment with increased inhaled corticosteroid. Upper airway adverse effects were minor and easily controlled. Hence, asthma with persistent symptoms was better controlled by increased inhaled corticosteroid therapy than by increased use of inhaled beta-agonist. PMID- 1446478 TI - Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. AB - BACKGROUND: Previous study of patients with chronic fatigue syndrome (CFS) has demonstrated a markedly reduced dynamic exercise capacity, not limited by cardiac performance and in the absence of clinical neuromuscular dysfunction, suggesting the possibility of a subclinical defect of skeletal muscle. METHODS: The in vivo metabolism of the gastrocnemius muscles of 22 CFS patients and 21 normal control subjects was compared during rest, graded dynamic exercise to exhaustion and recovery, using 31P nuclear magnetic resonance (NMR) spectroscopy to reflect minute-to-minute intracellular high-energy phosphate metabolism. RESULTS: Duration of exercise was markedly shorter in the CFS patients (8.1 +/- 2.8 min) compared with the normal subjects (11.3 +/- 4.3 min) (p = 0.005). There were large changes in phosphocreatine (PCr), inorganic phosphate (Pi), and pH from rest to clinical fatigue in all subjects, reflecting the high intensity of the exercise. The temporal metabolic patterns were qualitatively similar in the CFS patients and normal subjects. There were early and continuous changes in PCr and Pi that peaked at the point of fatigue and rapidly reversed after exercise. In contrast, pH was relatively static in early exercise, not declining noticeably until 50 percent of total exercise duration was achieved, and reaching a nadir at 2 min postexercise, before rapidly reversing. There were no differences in pH at rest (7.08 +/- 0.04 vs 7.10 +/- 0.04), exhaustion (6.85 +/- 0.17 vs 6.76 +/- 0.17) or early (6.64 +/- 0.25 vs 6.56 +/- 0.24) or late recovery (7.09 +/- 0.04 vs 7.10 +/- 0.05), CFS patients vs normal subjects, respectively (NS). Neither were there intergroup differences (NS) in PCr or Pi. Although, quantitatively, the changes in PCr, Pi, and pH were marked and similar in both groups from rest to exhaustion, the changes all occurred much more rapidly in the CFS patients. Moreover, adenosine triphosphate (ATP) was significantly (p = 0.007) less at exhaustion in the CFS group. CONCLUSIONS: Patients with CFS and normal control subjects have similar skeletal muscle metabolic patterns during dynamic exercise and reach similar clinical and metabolic end points. However, CFS patients reach exhaustion much more rapidly than normal subjects, at which point they also have relatively reduced intracellular concentrations of ATP. These data suggest a defect of oxidative metabolism with a resultant acceleration of glycolysis in the working skeletal muscles of CFS patients. This metabolic defect may contribute to the reduced physical endurance of CFS patients. Its etiology is unknown. Whether CFS patients' overwhelming tiredness at rest has a similar metabolic pathophysiology or etiology also remains unknown. PMID- 1446479 TI - Lung cancer in young adults. AB - OBJECTIVE: To define the basis for the conflicting reports on the prognosis of lung cancer in young adults. DESIGN: Retrospective review of lung cancer patients between 1977 and 1988. SETTING: Medical centers in Chicago (Northwestern Memorial Hospital), northern Israel (Rambam Medical Center), and northern Italy (S. Anna and U. of Pavia Hospitals). PATIENTS: Patients were < or = 45 years of age with a diagnosis of primary lung cancer identified from tumor registry records, pathology reports, and hospital charts, plus a sample of patients > 45 years of age. MEASUREMENTS AND MAIN RESULTS: In Chicago, younger patients had a higher incidence of chest pain, fever, and neurologic symptoms at presentation than the older patients, and fewer were asymptomatic. They also had more lower lobe lesions on chest roentgenogram, a higher incidence of adenocarcinoma, more advanced disease, an increased likelihood of receiving chemotherapy, and reduced survival (p < 0.03). The poorer prognosis was due to more advanced disease at presentation. In Israel, younger patients more frequently presented with stage I disease than the older patients and they had a higher incidence of adenocarcinoma, an increased likelihood of receiving treatment especially surgery, and better survival (p < 0.02). There were no differences between the two age groups for symptoms, symptom duration, and chest roentgenogram findings. Compared with the younger patients in Chicago and Israel, those from northern Italy had more squamous cell cancers and fewer adenocarcinomas, more commonly presented with stage I or II disease, received radiation therapy less frequently, and were given supportive care more often. Survival was low and comparable to that reported from Chicago. CONCLUSION: Differences exist in the clinical characteristics, pathologic findings, and prognosis of younger and older patients with lung cancer from the same region and of younger patients from different regions. The difference in prognosis is related in part to the stage of disease at presentation and the ability to undergo resectional surgery. PMID- 1446480 TI - Reduction of pulmonary surfactant in patients with human immunodeficiency virus infection and Pneumocystis carinii pneumonia. AB - We assessed qualitative and quantitative differences in surfactant lipid composition of bronchoalveolar lavage (BAL) fluid in patients with acquired immune deficiency syndrome (AIDS) and Pneumocystis carinii (PC) pneumonia. Five normal volunteers and 27 patients with human immunodeficiency virus (HIV) infection underwent BAL for evaluation of possible pulmonary infection. Bronchoalveolar lavage studies in eight patients were negative for PC organisms, and 19 were positive. Pneumocystis carinii pneumonia was graded (mild vs moderate to severe) by initial alveolar-arterial oxygen gradient. Bronchoalveolar lavage fluid was centrifuged, the lipids were extracted from the supernatant, and total lipid profiles of dephosphorylated glycerolipids were analyzed as trimethylsilylether derivatives by high temperature gas-liquid chromatography. Phospholipase A2 levels were determined using a radiolabeled E coli membrane method. Compared to the normal volunteers (109 +/- 13 micrograms/5 ml) and the PC negative group (107 +/- 13 micrograms/5 ml), total BAL lipid was reduced for both the mild PC pneumonia group (73 +/- 10 micrograms/5 ml) and the moderate to severe PC pneumonia group (46 +/- 4 micrograms/5 ml). There was a parallel reduction of diacylglycerol lipids: normal volunteers, 52 +/- 7 micrograms/5 ml; PC negative, 52 +/- 9 micrograms/5 ml; mild PC pneumonia, 35 +/- 7 micrograms/5 ml; and moderate to severe PC pneumonia, 15 +/- 2 micrograms/5 ml. Phospholipase A2 activity in moderate to severe PC pneumonia was twice that of the PC negative patients, and 30 times that for normals. The data demonstrate a marked diminution in surfactant glycerophospholipid in patients with AIDS and PC pneumonia and suggest a potential role for surfactant abnormality in the pathophysiology of this disease. PMID- 1446481 TI - Time course of pulmonary function before admission into ICU. A two-year retrospective study of COLD patients with hypercapnia. AB - Changes in cardiopulmonary function were retrospectively evaluated back to two years before acute exacerbations requiring ICU admission in 16 COLD patients with chronic hypercapnic respiratory insufficiency (age: 61 +/- 6 years, group A). Fifteen hypercapnic COLD patients matched for age, sex, lung function, and blood gas values not requiring an ICU admission in a period of two years, served as control subjects (age: 66 +/- 7, group B). Periodic assessments of spirometry, arterial blood gas values, echocardiography, body weight, and red blood cell count performed in stable state were compared for differences between groups and changes over a period of two years. The results indicated that basal body weight, rate of deterioration over time in FEV1, VC, blood gas values, bicarbonates, and RVD may be related to the necessity of ICU admission in COLD patients with hypercapnic respiratory insufficiency. PMID- 1446482 TI - Resuscitation from severe acute hypercapnia. Determinants of tolerance and survival. AB - A 46-year-old man underwent cosmetic facial surgery under general anesthesia. He was ventilated by mask with an oxygen-enriched gas mixture for 4 to 6 h and monitored by pulse oximetry. Despite adequate arterial saturation (SaO2 > 90 percent) throughout the procedure, he remained in a deep coma after termination of anesthesia. Initial arterial blood gas analysis revealed a pH of 6.60 and a PaCO2 of 375 mm Hg. The patient was intubated and placed on mechanical ventilation. As his respiratory acidosis resolved, he regained consciousness quickly and recovered without any neurologic deficits. This case of record extreme hypercapnia and review of the literature demonstrates that survival is possible in acute severe respiratory acidosis as long as tissue anoxia and ischemia are prevented. We discuss the tissue effects of acute hypercapnia and newer aspects of the nature of intracellular pH regulation in critical tissues that afford considerable tolerance to acidosis. The dependence of these mechanisms upon active ion transport underscores the importance of adequate tissue oxygenation and perfusion. PMID- 1446483 TI - Large pericardial effusions in the acquired immunodeficiency syndrome. AB - The increasing importance of the acquired immunodeficiency syndrome (AIDS) as a cause of large, clinically significant pericardial effusions has not been well documented. To determine the frequency and characteristics of large AIDS associated pericardial effusions, we reviewed the records of 50 consecutive patients undergoing pericardiocentesis between 1985 and 1990; AIDS was the most common underlying illness and was present in 14 patients (28 percent). The pericardial fluid was diagnostic in three (21 percent) of the 14 cases (one bacterial, one positive for acid-fast bacilli, and one lymphoma). Of the 11 patients with nondiagnostic fluid, one underwent a pericardial biopsy which revealed granuloma consistent with mycobacterial disease, four had active pulmonary tuberculosis (TB), and two responded clinically to anti-TB therapy. Thus, in 8 (57 percent) of the 14 patients with AIDS, there was either definitive or suggestive evidence of mycobacterial disease. We conclude that AIDS is now a common underlying illness associated with large pericardial effusions and that mycobacterial disease may frequently be the etiology. PMID- 1446484 TI - The relationship of clinical findings to CT scan evidence of adrenal gland metastases in the staging of bronchogenic carcinoma. AB - OBJECTIVE: To determine whether, during the staging of newly diagnosed bronchogenic carcinoma, clinical indicators predict the presence or absence of adrenal metastases detected by computerized tomographic (CT) scans. DESIGN: Retrospective review of charts and roentgenograms. SETTING: Academic medical center. PATIENTS: Two hundred five consecutive patients diagnosed with bronchogenic carcinoma, of whom 173 had sufficient data available for analysis. MEASUREMENTS: Charts were reviewed for abnormalities in three clinical categories (signs, symptoms, and routine laboratory tests) and the presence of extrapulmonary tumor spread. The CT scans were reviewed for evidence of adrenal involvement by radiologists blinded to clinical findings. MAIN RESULTS: Thirty patients had abnormal adrenal glands on CT scan. In 26 the abnormality was believed to represent adrenal metastasis, whereas in four the CT findings were consistent with adrenal adenomas. The frequency of adrenal metastases varied with the number of positive, clinical findings (chi 2 = 105.4; p < 0.001). All 26 patients with adrenal metastases had at least one clinical abnormality, and 21 (81 percent had abnormalities in either two or all three clinical categories. In 40 patients without any clinical indicators of widespread disease, none had CT evidence of adrenal metastases. The presence of adrenal metastases also varied with the extent of coexistent disease (chi 2 = 111.82; p < 0.001). Eighty-one percent (21) of the patients with and 18 percent of those without adrenal metastases had both intrathoracic and extrathoracic involvement. CONCLUSIONS: Our findings indicate that adrenal metastases are found in patients with a large tumor burden who have clinical indicators of widespread disease. We found no evidence of adrenal metastases by CT in any patient with a normal clinical evaluation. We conclude that CT scans through the adrenal glands are unnecessary when staging newly diagnosed bronchogenic carcinoma if the findings from the initial clinical evaluation are normal. PMID- 1446485 TI - Oscillatory mechanics of the respiratory system in neuromuscular disease. AB - Respiratory impedance measurements by means of the technique of forced oscillations together with spirometry and measurements of maximal mouth pressures were performed in 27 patients with a variety of neuromuscular disorders to assess the value of adding respiratory impedance measurements in the evaluation of lung function in neuromuscular disease. Using the technique of forced oscillations, impedance measurements are easily performed in physically disabled persons, since they require little active cooperation and no forced respiratory maneuvers. Normal respiratory impedance characteristics were found, although resistance values were somewhat higher than those found in normal subjects, signifying the absence of airflow limitation. Spirometric values were markedly reduced, as were maximal mouth pressures. No significant correlations were found between the forced expiratory volumes in 1 s (FEV1) and the impedance data. A strong curvilinear relationship was observed between Pemax and the RV/TLC ratio and a strong correlation existed between FEV1 and Premax. It is concluded from our study that forced oscillometry is a useful tool for the assessment or exclusion of airflow obstruction in patients with neuromuscular disorders when plethysmography is difficult to perform and forced expiratory flow-volume data reflect muscle weakness rather than airflow limitation. PMID- 1446486 TI - Efficacy of engineering controls in reducing occupational exposure to aerosolized pentamidine. AB - Aerosolized pentamidine administration may pose potential risks to health care workers exposed to fugitive drug and to infectious respiratory pathogens (eg, tuberculosis) generated by pentamidine-induced cough. Classic infection control methods may be applied to this problem, although the effectiveness of these measures in mitigating environmental pentamidine exposure is unknown. Lack of data fully characterizing pentamidine's mechanism of action or potential mutagenicity, carcinogenicity, or teratogenicity raises concern and suggests worker exposed and environmental contamination be minimized. We report herein on the efficacy of an aerosol containment hood in containing fugitive pentamidine aerosol during administration. PMID- 1446487 TI - Effect of inspiratory muscle fatigue on inspiratory muscle relaxation rates in healthy subjects. AB - Simple methods to diagnose inspiratory muscle fatigue in the clinical setting would be of considerable benefit. Inspiratory muscle relaxation rates are known to slow following induction of fatigue. Inspiratory muscle relaxation rates have been measured following a short sharp inspiratory effort against an occluded airway (sniffmouth) or through the unoccluded nostrils (sniffnostrils). Relaxation rates in the absence of fatigue are faster when sniffs are performed through the unoccluded nostrils. While both methods have been shown to be capable of detecting inspiratory muscle fatigue, there may be quantitative or qualitative differences between the two techniques in their ability to detect fatigue similar to the differences observed in the fresh state. Accordingly, we measured relaxation rates with the two sniff techniques in five healthy naive male subjects before and after induction of fatigue. Inspiratory muscle fatigue was induced by threshold loading at 80 percent of Pesmax until the subjects were unable to generate the target pressure. For those trials in which sniffnostrils were performed, the maximum relaxation rate from the esophageal pressure curve (MRRes) was significantly decreased following induction of fatigue in nine of ten trials, while the exponential time constant (taues) was significantly increased in all ten trials. In contrast, for those trials in which sniffmouth were performed, the MRRes was significantly decreased following induction of fatigue in only six of ten trials. Similarly, taues was significantly increased following induction of fatigue in only six of ten trials. In addition, the magnitude of change in the MRR or tau following induction of fatigue was quantitatively greater with sniffnostrils compared with sniffmouth. Similar findings were obtained when relaxation rates were measured from the diaphragmatic pressure tracing. In conclusion, changes in relaxation rate following induction of fatigue were quantitatively greater and more consistently observed when sniffs were performed through the unoccluded nostrils rather than against an occluded airway. PMID- 1446488 TI - Exercise testing, 6-min walk, and stair climb in the evaluation of patients at high risk for pulmonary resection. AB - To evaluate three types of exercise testing in prediction of death or prolonged mechanical ventilation after lung resection in high-risk patients, 16 patients underwent evaluation prior to resection. Eleven patients (group 1) had minor or no complications (arrhythmia, atelectasis, pneumonia) and five patients (group 2) died within 90 days of surgery. Exercise testing showed that group 1 had a longer 6-min walk distance and a higher stair climb than group 2. The maximum oxygen uptake on a cycle ergometer was not significantly different between groups, although only ten patients completed this test. Group 1 had a significantly greater calculated oxygen uptake with stair climbing than group 2. A 6-min walk distance of greater than 1,000 feet and a stair climb of greater than 44 steps were predictive of successful surgical outcome. Preoperative exercise testing is a useful adjunct to traditional spirometric testing in evaluation of the high risk surgical patients. PMID- 1446489 TI - Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization. AB - BACKGROUND: Supranormal mixed venous oxygen saturation (mixed venous hyperoxia), although reported, has never been characterized in humans resuscitated from cardiac arrest (postarrest cardiogenic shock). By contrast, cardiogenic shock without cardiopulmonary arrest (primary cardiogenic shock) is accompanied by mixed venous hypoxia under similar conditions of low oxygen delivery (DO2). The appearance of mixed venous hyperoxia indicates an excessive supply relative to demand in perfused tissue or cellular impairment of oxygen utilization, ie, low systemic oxygen consumption (VO2). Failure to improve VO2 has been associated with a poor outcome in other shock states. STUDY OBJECTIVE: This study evaluates the clinical significance of mixed venous hyperoxia and its implications for impaired systemic oxygen utilization. The oxygen transport patterns in surviving and nonsurviving cardiac arrest patients are compared for their prognostic and therapeutic implications. STUDY DESIGN: Consecutive, nonrandomized series. SETTING: Large urban emergency department (ED). PARTICIPANTS: Adult normothermic, nontraumatic out-of-hospital cardiac arrest patients presenting to the ED who develop a return of spontaneous circulation (ROSC). INTERVENTIONS: On arrival to the ED, a fiberoptic catheter was placed in the central venous position for continuous central venous oxygen saturation monitoring (ScvO2). A proximal aortic catheter was placed via the femoral artery for blood pressure monitoring. Upon ROSC, the fiberoptic catheter was advanced to the pulmonary artery. Mean arterial pressure (MAP), cardiac index (CI), VO2, DO2, systemic oxygen extraction ratio (OER), and systemic vascular resistance index (SVRI-dynes.s/cm5.m2) were measured immediately and every 30 min. The duration of cardiac arrest (DCA) in minutes and amount of epinephrine (milligrams) administered during ACLS was recorded. MEASUREMENTS AND RESULTS: Twenty-three patients were entered into the study. Survivors (living more than 24 h) and nonsurvivors (living less than 24 h) were compared. CONCLUSIONS: These findings indicate an impairment of systemic oxygen utilization in postarrest cardiogenic shock patients. In spite of a lower DO2 than survivors, the OER in nonsurvivors remained lower than expected. Venous hyperoxia is a clinical manifestation of this derangement. Epinephrine dose may have a causal relationship. The inability to attain a VO2 of greater than 90 ml/min.m2 after the first 6 h of aggressive therapy was associated with a 100 percent mortality in 24 h. PMID- 1446490 TI - Diagnostic value of hemosiderin-containing macrophages in bronchoalveolar lavage. AB - STUDY OBJECTIVE: Our objective was to determine if the hemosiderin content of BAL macrophages allows us to draw any differential diagnostic conclusions in a variety of lung diseases. PATIENTS AND STUDY DESIGN: One hundred one patients who underwent BAL for different diagnostic reasons were studied prospectively. MAIN RESULTS: The highest values for the hemosiderin score (HS) were found in patients with active alveolar hemorrhage and patients who had undergone heart transplantation for congestive heart failure. Compared to a control population, patients with Pneumocystis carinii pneumonia or invasive aspergillosis had a higher HS than patients with bacterial pneumonia or mycobacterial lung infection. High or intermediate values for HS were more often found in patients with a low than in those with a normal platelet count. CONCLUSIONS: The differential diagnostic conclusions which can be based on an HS are limited. PMID- 1446491 TI - The effects of powered air supply to the respiratory protective device on respiration parameters during rest and exercise. AB - The common chemical warfare protective masks impose an excessive respiratory load on the wearer due to elevated breathing resistance and increased dead space. For patients with severe respiratory disease, the excessive respiratory effort may be intolerable. Besides, the substantial negative pressure created within the mask during inspiration may result in an inward leakage in individuals having difficulties with proper facial fitting of the mask. The purpose of the current investigation was to evaluate the effects of a blower, actively driving air, through the mask's filter, at a flow (mean +/- SD) of 42 +/- 2 L/min, on respiratory parameters during rest and moderate exercise. Ten healthy subjects of either sex participated in two experimental sessions, wearing the mask with and without the blower. Each session included 6 min of sitting at rest and 6 min of walking on a treadmill (3.2 mph, and 10 percent grade). In nine of the subjects, the active air supply produced a positive inspiratory pressure at rest (5 +/- 4 vs -24 +/- 9 mm H2O peak inspiratory pressure with and without the blower, respectively, p < 0.0001). Inspiratory carbon dioxide concentration (FICO2) at rest was diminished (0.4 +/- 0.4 vs 1.3 +/- 0.7 percent with and without the blower, respectively; p < 0.01) while FIO2 increased from 19.5 +/- 0.7 percent to 20.6 +/- 0.4 percent with the device (p < 0.01). These changes were associated with a significant decrease in respiratory rate (15 +/- 2 vs 18 +/- 3 per minute, p < 0.01). During exercise the blower barely decreased the negative inspiratory pressures, had no effect on other respiratory parameters measured, but significantly shortened the inspiratory/cycle-length time ratio (0.46 +/- 0.03 vs 0.53 +/- 0.03, p < 0.005). The effects of active air supply were not different between male and female subjects. We conclude that the blower is expected to be a useful accessory to respiratory protective devices for patients with pulmonary disease. PMID- 1446492 TI - Liquid phase characteristics of bronchoalveolar lavage in primary Sjogren's syndrome. AB - We have previously reported that alveolitis correlates with clinical, roentgenologic, and functional parameters of pulmonary involvement in primary Sjogren's syndrome (1SS). In the present study, we analyzed the liquid phase characteristics of bronchoalveolar lavage (BAL) in the same 19 patients with 1SS. Our results show that patients with "high alveolitis" (group A, BAL lymphocytes > 15.2 percent) have increased values of total protein, albumin, IgA, and IgG and in their BAL fluid compared with patients with "low alveolitis" (group B) and control subjects. Also interleukin 2 (IL-2) was detected in more "high alveolitis" patients while IgM, IL-2R, and interferon gamma (IFN-gamma) were detected only in this group. There were no differences between the two groups in serum values of all above factors as well as in the presence of rheumatoid factor, extractable nuclear antibodies, and antinuclear antibodies. The increased values of immunoglobulins and cytokines in the BAL fluid of patients with intense alveolitis, in the absence of serum differences, speak for their local production and suggest activation of local immune mechanism. PMID- 1446493 TI - Human pleural effusions are rich in matrix metalloproteinases. AB - We identified and characterized type IV collagenase and gelatinase activity in pleural fluid from 32 patients. The capacity to substantially degrade type IV collagen was demonstrated in every pleural sample. Comparable results were also noted for the degradation of a radiolabeled gelatin substrate. Gelatin gel zymography of the pleural fluids revealed two prominent zones of lysis at 66 kDa and 92 kDa. These were identified by specific polyclonal antibodies as human matrix metalloproteinases MMP-2 and MMP-9. The concentration of MMP-2 in pleural fluid, as measured by enzyme-linked immunoassay, averaged 1,622 ng/ml whereas those of MMP-9 were 210 ng/ml. Substrate degradation activity was compared in both serum and pleural fluid from three patients and found to be similar. In serum this enzymatic activity was primarily due to MMP-9 whereas in pleural fluid, the predominant gelatinase was MMP-2. This was confirmed by immunoassay that showed that MMP-2 levels were two to five times higher in pleural fluid than in serum. We conclude that substantial amounts of MMP-2 and, to a lesser degree, MMP-9 are present in pleural effusions. The bioactivity and the immunoactivity of these enzymes did not help to distinguish among pleural fluids characterized as transudates, nonmalignant exudates, or malignant exudates. The differences in the distribution of these enzymes in pleural fluid and blood suggest that their presence is not due simply to the ultrafiltration of plasma, but rather to synthesis by the resident cells at the pleural surfaces. PMID- 1446494 TI - Prospective comparative study of ofloxacin or ethambutol for the treatment of pulmonary tuberculosis. AB - The efficacy of ofloxacin, rifampicin and isoniazid was prospectively compared with the regimen of ethambutol, rifampicin and isoniazid for the primary treatment of pulmonary tuberculosis in 124 patients. All drugs were given orally daily for nine months. Culture conversion rates three months after starting treatment were 98 percent in the ofloxacin group and 94 percent in the ethambutol group; by six months all patients in both groups were culture-negative. Significant radiological improvement of pulmonary infiltrates was observed in 83 percent of the ofloxacin group and 85 percent of the ethambutol group one year after starting treatment. No relapse in either group was observed during a two year follow-up period after the cessation of chemotherapy. Ofloxacin appears to be as useful as ethambutol in the treatment of pulmonary tuberculosis when either drug is combined with isoniazid and rifampicin. PMID- 1446495 TI - Diagnostic value of sialic acid in malignant pleural effusions. AB - In this study, we measured pleural fluid and serum sialic acid levels in 70 consecutive patients hospitalized with pleural effusions and serum sialic acid concentrations in 20 healthy individuals chosen as control group. The cause of 26 pleural effusions was malignancy, and diseases other than malignant neoplasms were determined as the cause of 44 cases. Mean serum sialic acid levels in the patients with malignancies were higher than the levels in patients with nonmalignant diseases and the control group. Mean sialic acid level in the patients with nonmalignant diseases was increased compared with control group, but this increase was not as high as that in the patients with malignancies. In the patients with malignant neoplasms, mean pleural fluid sialic acid content was also higher than that found in other diseases. Sialic acid concentration of pleural fluid was correlated with serum concentration. However, pleural fluid to serum sialic acid ratio in malignant diseases was greater than that in the others. The specificity and sensitivity of pleural fluid sialic acid level in excess of 0.075 mg/ml in distinguishing malignant effusions were 68 percent and 77 percent, respectively. These values for pleural fluid/serum sialic acid ratio with the cut-off level of 0.7 were 55 percent and 65 percent. Our findings indicate that determination of sialic acid level in malignant pleural effusions has a diagnostic value. PMID- 1446496 TI - Multisystem organ failure predicts mortality of ICU patients with acute respiratory failure secondary to AIDS-related PCP. AB - OBJECTIVE: To evaluate the ability of a variety of scoring systems to predict mortality of patients admitted to an intensive care unit (ICU) with acute respiratory failure (ARF) secondary to AIDS-related Pneumocystis carinii pneumonia (PCP). METHODS: All patients with AIDS-related PCP admitted to ICU at St. Paul's Hospital between January 1, 1985 and April 1, 1991 were reviewed. For each case, the following scores were calculated from data obtained within 24 h of ICU admission: acute physiology and chronic health evaluation II (APACHE II); acute lung injury score; AIDS score as described by Justice and Feinstein; and modified multisystem organ failure (MSOF) score. The serum lactate dehydrogenase (LDH) level was also recorded when obtained within 24 h of ICU admission. RESULTS: A total of 52 ICU admissions in 51 patients were studied. Overall mortality was 65 percent. Mortality increased with increasing MSOF (p < 0.05) score and LDH (p < 0.05). Based on receiver operating characteristic (ROC) curves, the MSOF score and the LDH were found to be good predictors of mortality. Multivariate logistic regression showed that the MSOF score was the only independent predictor of mortality (p < 0.05). The AIDS score, APACHE II, and the acute lung injury score were not significantly associated with mortality. Addition of the serum LDH level improved the performance of both the MSOF and AIDS scores, though the AIDS score plus LDH performed no better than the LDH alone. Of all the scores tested, the MSOF plus LDH level was the best (p < 0.005) predictor of mortality. CONCLUSIONS: The modified MSOF score and the serum LDH level are the best predictors of mortality of patients admitted to ICU with ARF secondary to AIDS-related PCP. The performance of the MSOF score was enhanced when the LDH level was added. The AIDS score, APACHE II, and the acute lung injury score were not found to be useful in this group of critically ill patients. PMID- 1446497 TI - Reproducibility of weaning parameters. A need for standardization. AB - Although weaning parameters can accurately predict weaning outcome, variability of the measurements of these parameters has not been closely examined. In the current study, we examined the reproducibility of these parameters using a standardized technique. Before the weaning trial, maximal inspiratory pressure (PImax), minute ventilation (VE), respiratory frequency (f), tidal volume (VT), rapid shallow breathing index (f/VT), and vital capacity (VC) were obtained on three trials over a period of 15 min. The results of these parameters over three measurements were compared. There were no statistical differences in the values of PImax, VE, f, VT, and f/VT over three trials (p = 0.45, p = 0.37, p = 0.69, p = 0.64, p = 0.1, respectively). The VC was the only parameter that showed statistical differences among three trials (p < 0.05). For the group, respiratory frequency had the lowest coefficient of variation (COV = SD/mean x 100 percent) at 6.7 percent while the VC had the highest COV at 19.6 percent. We concluded that most weaning parameters of breathing pattern can be measured reliably with bedside instruments using a standard technique. PMID- 1446498 TI - A nurse-directed protocol using pulse oximetry to wean mechanically ventilated patients from toxic oxygen concentrations. AB - The usual method of weaning mechanically ventilated patients from high FIO2 in our ICU, in which housestaff ordered all ventilator changes in an unstandardized manner (control group), was compared to a nurse-directed protocol that used a single arterial blood gas (ABG) analysis and multiple pulse oximetry measurements. The protocol required an ABG to be obtained upon the initiation of intubation/mechanical ventilation, followed by pulse oximetry measurements obtained in accordance with a standardized timetable. Decreases in FIO2 were guided by these results. It was concluded that a nurse-directed oxygen weaning protocol utilizing a combination of a single ABG and multiple pulse oximetry measurements was safe, reduced the need for ABGs, and decreased the duration of patient exposure to toxic oxygen concentrations. PMID- 1446499 TI - Nitroprusside-related cyanide poisoning. Time (long past due) for urgent, effective interventions. PMID- 1446500 TI - Extracorporeal circulation as an alternative to open-chest cardiac compression for cardiac resuscitation. AB - Open-chest direct cardiac compression represents a more potent but highly invasive option for cardiac resuscitation when conventional techniques of closed chest cardiac resuscitation fail after prolonged cardiac arrest. We postulated that venoarterial extracorporeal circulation might be a more effective intervention with less trauma. In the setting of human cardiac resuscitation, however, controlled studies would be limited by strategic constraints. Accordingly, the effectiveness of open-chest cardiac compression was compared with that of extracorporeal circulation after a 15-min interval of untreated ventricular fibrillation in a porcine model of cardiac arrest. Sixteen domestic pigs were randomized to resuscitation by either peripheral venoarterial extracorporeal circulation or open-chest direct cardiac compression. During resuscitation, epinephrine was continuously infused into the right atrium, and defibrillation was attempted by transthoracic countershock at 2-min intervals. Systemic blood flows averaged 198 ml.kg-1.min-1 with extracorporeal circulation. This contrasted with direct cardiac compression, in which flows averaged only 40 ml.kg-1.min-1. Coronary perfusion pressure, the major determinant of resuscitability on the basis of earlier studies, was correspondingly lower (94 vs 29 mm Hg). Extracorporeal circulation, in conjunction with transthoracic DC countershock and epinephrine, successfully reestablished spontaneous circulation in each of eight animals after 15 min of untreated ventricular fibrillation. This contrasted with the outcome after open-chest cardiac compression, in which spontaneous circulation was reestablished in only four of eight animals (p = .038). We conclude that extracorporeal circulation is a more effective alternative to direct cardiac compression for cardiac resuscitation after protracted cardiac arrest. PMID- 1446501 TI - Mediastinal shift in an asymptomatic young man. PMID- 1446502 TI - Pleurodesis for nonmalignant pleural effusions. Recommendations. PMID- 1446503 TI - Predicting outcome after ICU admission. The art and science of assessing risk. PMID- 1446504 TI - The role of cardiopulmonary exercise testing in the selection of patients for cardiac transplantation. PMID- 1446505 TI - Dyspnea and muscle weakness in a 65-year-old woman. PMID- 1446506 TI - Thoracoscopic management of spontaneous pneumothorax. PMID- 1446507 TI - Lung sequestration. Diagnosis with ultrasound and triplex Doppler technique in an adult. AB - The application of chest US with triplex Doppler technique to detect the systemic feeding artery of lung sequestration in an adult patient is described. To our best knowledge, this is the first description of the use of this technique to diagnose pulmonary sequestration in adult patients. This 35-year-old man had necrotizing pneumonia with abscess formation at the left lower lobe. Chest US demonstrated a large tortuous vessel in the central part of the lesion. Spectral wave Doppler analysis showed that this vessel was a systemic feeding artery and had pulsatile arterial wave-form. The color Doppler mapping delineated the blood flow originating from the descending aorta and toward the lesion, thus confirming the diagnosis of pulmonary sequestration. We conclude that chest US with triplex Doppler technique is a valuable method in evaluating a patient with a pulmonary lesion who was thought to have lung sequestration before performing invasive aortography. PMID- 1446508 TI - Evolving aortic mass in a patient with sepsis and systemic embolization. Detection by transesophageal echocardiography. AB - An elderly patient with sepsis and systemic embolization is described. An intraluminal aortic mass was discovered by transesophageal echocardiography that appeared to be the source of infection in this patient. Transesophageal echocardiography can be a useful diagnostic test in patients with sepsis and systemic embolization of unknown etiology. PMID- 1446509 TI - Inflammatory pseudotumor of the heart with vasculitis and venous thrombosis. AB - Inflammatory pseudotumor (IPT) is a tumor-like reactive lesion of unknown etiology. An unusual case of intracardiac IPT with multisystemic involvement, including leukocytoclastic vasculitis, polyarthritis, and inferior vena cava thrombosis in a 17-year-old boy is reported. This unique combination may suggest that immune/autoimmune factors are important in the pathogenesis of IPT. PMID- 1446510 TI - Utility of transesophageal echocardiography in the conservative management of prosthetic valve endocarditis. AB - Prosthetic valve endocarditis is a formidable complication following cardiac valve replacement. Surgical intervention has resulted in a significant reduction in mortality when certain complications prevail. We report two such cases of prosthetic valve endocarditis in which the use of transesophageal echocardiography permitted close surveillance during medical therapy and thus avoided the need for surgical intervention. Therefore, with the improved ability to monitor disease progression with transesophageal echocardiography, nonsurgical management of prosthetic valve endocarditis remains an option. PMID- 1446511 TI - Tension pneumopericardium in an infant. AB - Pneumopericardium in newborns is most often a complication of mechanical ventilation and frequently results in fatal cardiac tamponade. We report the case of a mechanically ventilated 33-day-old full-term gestation infant with interstitial pneumonitis who developed tension pneumopericardium. Treatment includes lowering peak inspiratory pressure and decompressing the pericardial space with tube drainage following pericardiocentesis. PMID- 1446512 TI - Intravenous pentamidine-induced bronchospasm. AB - A 41-year-old man with AIDS developed a recurrence of Pneumocystis carinii pneumonia and was treated with intravenous pentamidine. This was associated with a significant bronchospastic reaction requiring treatment with an antihistamine and an aerosolized beta-agonist therapy. To our knowledge, this is the first report of bronchospasm induced by intravenous pentamidine. PMID- 1446513 TI - Paradoxical bradycardia during exercise and hypoxic exposure. The possible direct effect of hypoxia on sinoatrial node activity in humans. AB - We describe a patient with pulmonary emphysema who developed paradoxical cardiodeceleration not only during incremental exercise associated with hypoxemia but also during progressive hypoxic challenge. Since coronary angiogram revealed no abnormality, this unique phenomenon seemed to be due to the direct effect of hypoxia on the sinus node activity. PMID- 1446514 TI - Malignant lymphoma in a patient with relapsing bronchiolitis obliterans organizing pneumonia. AB - A case of relapsing bronchiolitis obliterans organizing pneumonia complicated by malignant lymphoma (four years after the diagnosis) is reported in a 58-year-old woman. To our knowledge, such an association has not been described previously in detail in the literature. PMID- 1446515 TI - Reversible left ventricular dysfunction induced by recurrent ventricular tachycardia. AB - Two cases of transient LV dysfunction associated with VT are described. Both patients had a history of palpitations of several years' duration without symptoms of congestive heart failure. The reason for presentation was an increase in frequency and duration of palpitation. Decreased LV wall motion, observed by 2DE, normalized shortly after treatment of the VT. Diffusely decreased LV wall motion is associated with frequent episodes of VT and may mimic DCM except that signs and symptoms of heart failure are absent. PMID- 1446516 TI - Coexistent sarcoidosis and HIV infection. A comparison of bronchoalveolar and peripheral blood lymphocytes. AB - A case of pulmonary sarcoidosis diagnosed in an human immunodeficiency virus (HIV)-infected man is reported. The transbronchial lung biopsy specimen revealed noncaseating granuloma. A comparison of the lymphocyte subsets in both peripheral blood and bronchoalveolar lavage fluid revealed a pattern more typical of HIV infection than of classic sarcoidosis. A course of prednisone led to improvement in symptoms, roentgenographic findings, lung volumes, and diffusion capacity. PMID- 1446517 TI - Mediastinal bronchogenic cyst. A cause of upper airway obstruction. AB - Although bronchogenic cysts may involve the mediastinum, they have rarely been responsible for significant upper airway obstruction. We describe a young man who had a rapidly expanding cervical mass due to the migration of a mediastinal bronchogenic cyst. Flow-volume loops confirmed the presence of a variable intrathoracic obstruction. The patient rapidly developed respiratory failure requiring urgent intubation and surgical resection. PMID- 1446518 TI - Thoracoscopic Nd:YAG laser resection of a solitary pulmonary nodule. AB - Advances in endoscopic surgical techniques and laser technology have expanded the role of thoracoscopy. We report a thoracoscopic resection of a benign pulmonary lesion. A 44-year-old man underwent a successful Nd:YAG laser-assisted thoracoscopic resection of a peripheral lung hamartoma. The patient's postoperative course was uncomplicated. Thoracotomy with its attendant morbidity was avoided. Continued success with thoracoscopic resection will have a significant impact on the management of select patients with peripheral, solitary pulmonary nodules. PMID- 1446519 TI - Reversible cardiac arrest related to late-onset coronary spasm after a positive ergonovine test. PMID- 1446520 TI - Hilar and mediastinal lymphadenopathy with hypersensitivity pneumonitis induced by penicillin. AB - A 54-year-old Japanese man demonstrated a sultamicillin-induced hilar and mediastinal lymphadenopathy with hypersensitivity pneumonitis. A positive lymphocyte stimulation test for sultamicillin and a decreased CD4/CD8 ratio of lymphocytes in BAL fluid suggested that an alteration in cell-mediated mechanisms was responsible for the patient's symptoms. PMID- 1446521 TI - Giant thoracoabdominal lymphangioma with features of lymphangiomyoma. AB - A 15-year-old girl who presented with cough and dyspnea was found to have a mediastinal tumor that clinically resembled a lymphangioma. The tumor was unusual for its large size and its histologic features, which showed smooth muscle proliferation, generally considered a feature of lymphangiomyoma. PMID- 1446522 TI - Sterile mediastinal gas mimicking abscess in aortic aneurysm repair. AB - Six weeks after aortic aneurysm repair, computed tomography (CT) showed mediastinal gas where absorbable gelatin sponge (Gelfoam) was used. A leukocyte scan labeled with indium 111, however, was normal and surgical exploration showed no infection. Sterile gas collections may be seen following absorbable gelatin sponge use many weeks after surgery and 111In-labeled leukocyte scanning may be a useful differential test. PMID- 1446523 TI - Pulmonary Hodgkin's disease in HIV-infected patient. Diagnosis by bronchoalveolar lavage. AB - We report herein the pulmonary recurrence of Hodgkin's disease coincidental with a marked decrease in the peripheral blood CD4 lymphocyte count in an HIV seropositive patient with alveolar consolidation on chest roentgenogram. The diagnosis of lung parenchyma involvement was made by bronchoalveolar lavage cell analysis and illustrates the reliability of Reed-Sternberg cell identification in bronchoalveolar lavage for the diagnosis of pulmonary localization of Hodgkin's disease. PMID- 1446524 TI - Thoracoscopy forum: continuing dialogue. PMID- 1446525 TI - Thoracoscopy forum: continuing dialogue. PMID- 1446526 TI - Thoracoscopy forum: continuing dialogue. PMID- 1446527 TI - Thoracoscopy forum: continuing dialogue. PMID- 1446529 TI - Thoracoscopy forum: continuing dialogue. PMID- 1446528 TI - Thoracoscopy forum: continuing dialogue. PMID- 1446530 TI - Thoracoscopy forum: continuing dialogue. PMID- 1446531 TI - Hydatidosis with pericardial involvement. PMID- 1446532 TI - Air embolism during attempted central line placement. PMID- 1446533 TI - Apical Pneumocystis carinii pneumonia associated with HIV infection. PMID- 1446534 TI - Primary pulmonary hypertension in HIV infection. PMID- 1446535 TI - Diagnosis of mycobacterial mediastinal lymphadenopathy by transbronchial needle aspiration. PMID- 1446536 TI - The APACHE III prognostic system. PMID- 1446537 TI - Magnetic resonance imaging of thymic squamous cell carcinoma. PMID- 1446538 TI - Reexpansion pulmonary edema. PMID- 1446539 TI - Pulmonary toxicity following exposure to methylene chloride and its combustion product, phosgene. PMID- 1446540 TI - Thoracoscopic talc poudrage. Comparison with tetracycline and use in Hodgkin's disease. PMID- 1446541 TI - Children of lesbian and gay parents. AB - This paper reviews research evidence regarding the personal and social development of children with gay and lesbian parents. Beginning with estimates of the numbers of such children, sociocultural, theoretical, and legal reasons for attention to their development are then outlined. In this context, research studies on sexual identity, personal development, and social relationships among these children are then reviewed. These studies include assessment of possible differences between children with gay or lesbian versus heterosexual parents as well as research on sources of diversity among children of gay and lesbian parents. Research on these topics is relatively new, and many important questions have yet to be addressed. To date, however, there is no evidence that the development of children with lesbian or gay parents is compromised in any significant respect relative to that among children of heterosexual parents in otherwise comparable circumstances. Having begun to respond to heterosexist and homophobic questions posed by psychological theory, judicial opinion, and popular prejudice, child development researchers are now in a position also to explore a broader range of issues raised by the emergence of different kinds of gay and lesbian families. PMID- 1446542 TI - Multiple influences on the acquisition and socialization of children's health attitudes and behavior: an integrative review. AB - An overview and synthesis of the literature documenting various influences on the socialization and acquisition of children's health attitudes and behavior is the focus of this review. Cognitive-developmental approaches to understanding children's health attitudes are presented, followed by an exploration of an individual differences perspective on children's acquisition of health attitudes and behavior. The influence of various socialization agents, including families, peers, schools, and the media, on children's acquisition of health attitudes and behavior is considered. Implications of these findings for social policy, future research, and modeling of child health attitudes and behavior are examined. PMID- 1446543 TI - The development of category-based induction. AB - In a category-based induction, knowing that a property is true of some category members leads one to conclude that the property is true of other category members. An example is: Cardinals have ulnar arteries. Therefore hawks have ulnar arteries. Recently, Osherson et al. (1990) demonstrated a number of phenomena involving category-based inductions, and proposed that these phenomena can be explained by variations in 2 processes: (a) the similarity between the premise category (cardinals in the above example) and the conclusion category (hawks in the above example), and (b) the degree to which the premise category "covers" (roughly, is similar to) instances of the lowest-level category that includes both the premise and conclusion categories (birds in the above example). The present paper traces the developmental course of the relevant phenomena and of the similarity and coverage processes that presumably underlie them. Studies 1 and 2 demonstrated that the inductions made by kindergartners are sensitive only to the similarity between the premise and conclusion categories. Studies 3 and 4 showed that second graders' inductions are sensitive to both premise-conclusion similarity and coverage, as long as there is no need actually to use a generated category that includes both the premise and conclusion categories. These developmental findings reveal an orderly process in the growth of category-based inductions, and also decompose the Osherson et al. model into 3 basic components that have not previously been explicitly distinguished. PMID- 1446544 TI - Infant information processing in relation to six-year cognitive outcomes. AB - As part of a longitudinal follow-up of full-terms and preterms, infant measures of information processing obtained at 7 months and 1 year were related to various 6-year outcomes: general intelligence, language proficiency, early reading and quantitative skills, and several facets of perceptual organization (N = 91). 7 month Visual recognition memory (VRM) was associated with 6-year performance in all domains, and 3 1-year measures--VRM, cross-modal transfer (CMT), and object permanence--were related to IQ and/or one or more specific outcomes (r's = .20 to .47). Many of the infant-childhood relations remain significant even with IQ partialed. Additionally, 7-month VRM and 1-year CMT scores were lower for infants who, at 6 years, were considered at risk for learning disabilities. Overall, measures from the first year of life predicted both specific cognitive abilities and IQ at 6 years; to some extent, the specific abilities were predicted independently of IQ. PMID- 1446545 TI - The relations between frontal brain electrical activity and cognitive development during infancy. AB - The relations between changes in the scalp-recorded electroencephalogram (EEG) and the development of the ability to perform successfully 2 cognitive tasks attributed to frontal lobe functioning were examined in 13 infants from 7 to 12 months of age. Infants successful in performing the A-not-B task with increasingly longer delays across the second half of the first year of life showed changes in power in scalp-recorded brain electrical activity in the frontal region and an increase in anterior/posterior EEG coherence. Infants with rapid mastery of object retrieval did not differ in frontal EEG development from infants who exhibited the normal developmental progression in object retrieval performance. In a task examining inhibition of reaching to a novel toy, there were no differences in frontal EEG as a function of performance. Results from a cross-sectional sample revealed similar findings. These data confirm work with nonhuman primates on the importance of maturation of frontal cortex in the successful performance on certain tasks (A-not-B), but do not confirm nonhuman primate data on the importance of frontal cortex for other tasks (object retrieval). The data also suggest that the electroencephalogram may be useful as a noninvasive measure of central nervous system development during the first year of life. PMID- 1446546 TI - Integration of sequential information for shape perception by infants: a developmental study. AB - Perception of form by spatiotemporal integration was investigated in 3 experiments. In the first, infants aged 8, 10, and 12 months were tested using a novelty-preference procedure to determine the earliest age at which recognition of rectilinear and curvilinear form occurred. Infants were shown a light-point tracing of the outline of a figure, followed by simultaneous presentation of 2 test objects, one of the same shape as the tracing and one of a different shape. The tracing was double the size of the test objects. Only infants in the oldest group responded selectively by looking longer at the object of different shape. In the second experiment with 12-month-old infants only, it was shown that recognition of rectilinear, but not curvilinear, form occurred despite a difference in the orientation and size of tracing and object. Computer-generated tracings were used in the final experiment to compare form recognition for 2D and 3D stimuli. Selective responding occurred only for the latter. These findings show that by 12 months infants perceive the correspondence between the figural properties of a tracing and its extended form, but that this perception is dependent on the provision of depth cues. PMID- 1446547 TI - Early ontogeny of vocal behavior of Japanese infants in response to maternal speech. AB - Discriminant analysis was used to distinguish statistically between the comfort state vocalizations uttered by Japanese infants following 5 different types of pitch contours of maternal speech. Ontogenetic changes of their vocal behaviors were investigated during the first 5 months of life. Structural variability in infant vocalizations across variants of maternal speech was found to be characterized by a set of quantifiable physical parameters. However, infant's age when a vocalization was recorded was not an important contributor. Successful attempts at cross-validation, in which the discriminant profiles derived from one sample of vocalizations were used to classify a second set of vocalizations, indicated that the result obtained was not an artifact of using the same data set to derive the profiles to test reclassification accuracy. Proportion of cross validated vocalizations that were misclassified decreased as age increased. The results of the present study demonstrate that a statistically significant relation exists between acoustic features of maternal speech and those of following infant vocalizations, and that such a relation strengthens over age. PMID- 1446548 TI - Intentional behavior and intentional communication in young free-ranging orangutans. AB - The goal of this study was to describe the ontogeny of the manipulation of an animate object (i.e., the mother) by young free-ranging orangutans within the context of food sharing. The food-sharing context is an important one in the development of object manipulation skills and social communication. 5 orangutans, ranging in age from 1 month to 5 years, were videotaped with their biological mothers for 18 hours over the course of 9 months. Systematic coding of the videotapes revealed that even young orangutans, 1-6 months old, used intentional (i.e., goal-directed) behaviors. When young orangutans directed behavior toward the mother in addition to the goal object then maternal responses were positive, resulting in the infant obtaining the food. Intentional communication, evident in gestures and consisting of an abbreviated action directed toward the mother, was found in the 3 oldest orangutans (2 1/2, 3 1/2, and 5 years of age). Cognitive competence and behavioral performance are considered from the developmental perspectives of Piaget and prelinguistic communication. The ability to use a communicative gesture as an intermediate means in the coordination of actions on a social agent with actions on an object is evident in young orangutans. PMID- 1446549 TI - Preterm children at early adolescence and continuity and discontinuity in maternal responsiveness from infancy. AB - Patterns in mother-child interaction from infancy to age 12 were investigated in a prospective, longitudinal study of 44 English-speaking mothers and their preterm children. Maternal responsiveness was assessed by home observations during infancy and the Family Interaction Q-Sort at age 12, derived from 2 structured laboratory situations requiring cooperation of mother and child. A cluster of maternal behaviors of critical control toward the toddler was assessed at age 2 years. Children of mothers who were consistently more responsive during both infancy and early adolescence, as well as children whose mothers became more responsive by age 12, achieved higher IQ and arithmetic scores, had more positive self-esteem, and their teachers reported fewer behavioral and emotional problems than children of mothers who were consistently less responsive both during infancy and at age 12. Continuity in parenting behaviors was related to control and criticism beginning in the toddler period and not to degree of responsiveness to the infant. PMID- 1446550 TI - The contribution of mother-child and father-child relationships to the quality of sibling interaction: a longitudinal study. AB - Although several studies have now examined the relations between mother-child and sibling interaction, the role of fathers in the development of sibling relationships is noticeably absent. The present study included assessments of both mother-child and father-child interaction in order to examine the correlates of sibling conflict and cooperation. Home observations of parent-child and sibling interaction and reports of differential parental treatment were obtained for 30 families with 2 preschool children when the firstborns were approximately 6 years old. Earlier assessments of infant-mother and infant-father attachments when firstborns were 12 and 13 months old, respectively, were also available, as were prior laboratory assessments of mothering and fathering when the oldest child was 3 years of age. Results suggested that sibling conflict and aggression were related to high levels of conflict between the mother and the 2 children at 6 years, intrusive and overcontrolling mothering at 3 years, and an insecure infant-mother attachment. Facilitative and affectionate fathering, on the other hand, was associated with prosocial sibling interaction. Early relationship experiences between parents and their firstborn children had an enduring effect on the quality of sibling relationships and interacted with differential parental treatment in predicting sibling relationship outcomes. PMID- 1446551 TI - Self-regulatory mechanisms governing gender development. AB - This study tested predictions about development of gender-related thought and action from social cognitive theory. Children at 4 levels of gender constancy were assessed for their gender knowledge, personal gender standards, and gender linked behavior under different situational conditions. Irrespective of gender constancy level, all children engaged in more same-sex than cross-sex typed behavior. Younger children reacted in a gender stereotypic manner to peers' gender-linked behavior but did not regulate their own behavior on the basis of personal gender standards. Older children exhibited substantial self-regulatory guidance based on personal standards. They expressed anticipatory self-approval for same-sex typed behavior and self-criticism for cross-sex typed behavior. Their anticipatory self-sanctions, in turn, predicted their actual gender-linked behavior. Neither gender knowledge nor gender constancy predicted gender-linked behavior. These results lend support to social cognitive theory that evaluation and regulation of gender-linked conduct shifts developmentally from anticipatory social sanctions to anticipatory self-sanctions rooted in personal standards. PMID- 1446552 TI - Impact of parenting practices on adolescent achievement: authoritative parenting, school involvement, and encouragement to succeed. AB - This article examines the impact of authoritative parenting, parental involvement in schooling, and parental encouragement to succeed on adolescent school achievement in an ethnically and socio-economically heterogeneous sample of approximately 6,400 American 14-18-year-olds. Adolescents reported in 1987 on their parents' general child-rearing practices and on their parents' achievement specific socialization behaviors. In 1987, and again in 1988, data were collected on several aspects of the adolescents' school performance and school engagement. Authoritative parenting (high acceptance, supervision, and psychological autonomy granting) leads to better adolescent school performance and stronger school engagement. The positive impact of authoritative parenting on adolescent achievement, however, is mediated by the positive effect of authoritativeness on parental involvement in schooling. In addition, nonauthoritativeness attenuates the beneficial impact of parental involvement in schooling on adolescents achievement. Parental involvement is much more likely to promote adolescent school success when it occurs in the context of an authoritative home environment. PMID- 1446553 TI - Support from spouse as mediator and moderator of the disruptive influence of economic strain on parenting. AB - A model is presented regarding associations between economic strain, support from spouse, and quality of parenting. The model was tested using a sample of 451 2 parent families, each of which included a seventh grader (age 12-13). Parent and adolescent reports, as well as observational ratings, were used as indicators of constructs. Analysis using structural equation modeling procedures indicated that level of spouse support was positively related to supportive parenting, whereas economic strain operated to undermine parental involvement. As posited, economic strain produced its effect through a direct relation with parenting and indirectly through its association with spouse support. These findings held for mothers and fathers, regardless of the gender of the child. Spouse support moderated the impact of economic strain on supportive parenting for mothers but not fathers. Possible explanations for this gender difference are presented. PMID- 1446554 TI - Social information processing in aggressive and depressed children. AB - Social information processing patterns of children who were identified as being aggressive or depressed, both, or neither were compared in order to address the issue of specificity and to explore whether children who are comorbid show a unique processing style. Subjects were 220 children in the third through sixth grade. Peer nomination and teacher ratings were used to assess level of aggression, and the Children's Depression Inventory was used to measure level of depression. Aggressive children showed a hostile attributional bias, were more likely to report that they would engage in aggressive behavior, and indicated that aggression would be easy for them. Depressed children similarly showed a hostile attributional bias, although they were more likely to attribute negative situations to internal, stable, and global causes. Depressed children also reported that they would be less likely to use assertive responses and that they expected that assertive behavior would lead to more negative and fewer positive outcomes. Children who were comorbid generally showed patterns similar to both aggressive and depressed children. PMID- 1446555 TI - Some consequences of early harsh discipline: child aggression and a maladaptive social information processing style. AB - Although a number of studies have reported a relation between abusive parental behavior and later aggressive behavior in the victim, many of these investigations have had methodological limitations that make precise interpretation of their results problematic. In the present study, we attempted to determine whether harsh parental discipline occurring early in life was associated with later aggression and internalizing behavior in children, using a prospective design with randomly selected samples to avoid some of these methodological difficulties. Structural equation modeling indicated a consistent relation between harsh discipline and aggression in 2 separate cohorts of children. This relation did not appear to be due to possible confounding factors such as child temperament, SES, and marital violence, although there was some indication in our data that the latter variables were related to child aggression. In addition, our analyses suggested that the effect of harsh discipline on child aggression may be mediated at least in part by maladaptive social information processing patterns that develop in response to the harsh discipline. PMID- 1446556 TI - Cognitive mechanisms in children's gender stereotyping: theoretical and educational implications of a cognitive-based intervention. AB - The study was designed to test the hypothesis derived from cognitive developmental theory that multiple classification skill plays an important role in children's gender stereotyping and in their processing of counterstereotypic gender information. Children (N = 75; 5-10 years) were matched on pretest measures of gender stereotyping and multiple classification skill and then assigned to: (1) multiple classification training using nonsocial stimuli, (2) multiple classification training using social stimuli, (3) a rule training intervention, or (4) a control intervention. Children who had acquired multiple classification skill via training with social stimuli and those children trained on rules for occupational sorting showed significantly more egalitarian responding on a subsequent measure of gender stereotyping and superior memory for counterstereotypic information embedded in stories. Additionally, children who had acquired multiple classification skill via training with nonsocial stimuli showed superior memory for counterstereotypic information, despite demonstrating no greater flexibility on the gender stereotyping measure. Both theoretical and educational implications of results are discussed. PMID- 1446557 TI - Beyond beliefs: parent and child behaviors and children's perceived academic competence. AB - Examined the relations of parent and child behaviors with children's perceptions of their academic competence. 74 high-achieving third-grade children, with varying levels of perceived academic competence, were observed working with mothers and fathers both on solvable tasks (Period 1) and during a period that included some unsolvable tasks (Period 2). Results indicated that children's perceived academic competence was positively related to father warmth, both at Period 1 and at Period 2. Children's perceived academic competence was also positively related to their own behavior when working with fathers at Period 2. Specifically, children with higher perceived academic competence showed more emotional restraint and were more self-reliant when working on tasks at Period 2 than were children with lower perceived academic competence. The results indicate that there are systematic, observable correlates of children's self-reports of their perceived academic competence. PMID- 1446558 TI - The cross-ethnic equivalence of parenting and family interaction measures among Hispanic and Anglo-American families. AB - Recently there has been concern over the need for developmental research within ethnic minority populations and interest in family processes within, and variability across, ethnic groups. Unfortunately, most of the research using standard scales of family processes has sampled middle-class Anglo-Americans, and the potential absence of cross-ethnic measurement equivalence threatens the validity of the research using these scales with ethnic minority populations. This study reports confirmatory factor analyses and construct validity coefficients for several parenting and family interaction scales among Anglo American and Hispanic 8-14-year-old children and mothers. The findings indicate that the Children's Report of Parental Behavior Inventory (except the hostile control subscale), the Parent-Adolescent Communication Scale (open communication subscale only), and the Family Adaptability and Cohesion Evaluation Scales II appear to have sufficient cross-ethnic equivalence for English-speaking Hispanic samples. Further, the Family Routines Inventory and the problem communication subscale could benefit from additional scale development. PMID- 1446559 TI - Children's relationships with maternal grandparents: a longitudinal study of family structure and pubertal status effects. AB - This longitudinal study assessed the effects of parents' marital transitions and pubertal development on grandparent-grandchild relationships. 9- to 13-year-old children, their mothers, and maternal grandparents from 186 Caucasian, middle class families including 73 intact families, 64 mother-custody, single-parent families and 49 stepfamilies completed questionnaires focusing on the degree of children's "relationship involvement" (perceived closeness and frequency of contact) with maternal grandparents at 2 time periods 13 months apart. Children also completed questionnaires 9 months later during a third interview. Grandparents, and especially grandfathers, were more involved with grandchildren from single-parent families (supporting the "latent function" hypothesis). The pubertal status results supported the "emotional distancing" hypothesis for grandfather-granddaughter relationships (higher pubertal status, less involvement) and the "stress buffer" hypothesis for grandsons' relationships with both grandparents (greater change in physical development, more involvement and greater perceived closeness). PMID- 1446560 TI - Young children and television: the retention of emotional reactions. AB - In 6 experiments, we examined preschoolers' ability to interpret or remember the affective reactions of television characters. In 2 studies, children viewed a "Sesame Street" or "Cosby Show" segment, and then retold the story. In both, mention of the protagonists' affective states was low, with less than 1% of the reactions recalled. In 3 experiments (using muppet, cartoon, or human portrayals), we examined whether this low retention was due to an inability to interpret reactions, identify their emotional labels, or remember them across a short period. For muppet and cartoon shows, children accurately recognized labels for reactions immediately after portrayal, but showed significant reductions in recognition memory by the end of the show. For human portrayals, subjects showed accurate recognition immediately after presentation, as well as after the show. In a final experiment, free descriptions of the reactions were assessed. Correct description was significantly higher for basic emotions than complex emotions. PMID- 1446561 TI - Temperament, emotion, and cognition at fourteen months: the MacArthur Longitudinal Twin Study. AB - 200 pairs of twins were assessed at 14 months of age in the laboratory and home. Measures were obtained of temperament, emotion, and cognition/language. Comparisons between identical and fraternal twin correlations suggest that individual differences are due in part to heritable influences. For temperament, genetic influence was significant for behavioral observations of inhibition to the unfamiliar, tester ratings of activity, and parental ratings of temperament. For emotion, significant genetic influence was found for empathy and parental ratings of negative emotion. The estimate of heritability for parental report of expression of negative emotions was relatively high, whereas that for expression of positive emotions was low, a finding consistent with previous research. For cognition and language, genetic influence was significant for behavioral indices of spatial memory, categorization, and word comprehension. Shared rearing environment appears influential for parental reports of language and for positive emotions, but not for other measures of emotion or for temperament. PMID- 1446562 TI - The relations among infant temperament, security of attachment, and behavioral inhibition at twenty-four months. AB - The purpose of this study was to examine the relations among infant temperament, attachment, and behavioral inhibition. 52 infants were seen at 2 days, 5, 14, and 24 months of age. Assessments were made of temperament at 2 days and 5 months of age, and attachment and behavioral inhibition were assessed at 14 and 24 months, respectively. EKG was recorded at each assessment, and measures of heart period and vagal tone were computed. Distress to pacifier withdrawal at 2 days of age was related to insecure attachment at 14 months. 2 types of distress reactivity at 5 months, reactivity to frustration and reactivity to novelty, were identified and related to high vagal tone. Attachment classification at 14 months was directly related to inhibited behavior at 24 months. Infants classified as insecure/resistant were more inhibited than those classified as insecure/avoidant. In addition, an interaction of infant reactivity to frustration and attachment classification was found to predict inhibition at 24 months. Infants classified as insecure/resistant and who had not cried to the arm restraint procedure at 5 months were the most inhibited at 24 months. These findings are discussed in terms of hypotheses regarding multiple modes of distress reactivity and regulation in early infancy and their different social and behavioral outcomes. PMID- 1446563 TI - Psychophysiology in attachment interviews: converging evidence for deactivating strategies. AB - By asking the subject to consider a host of potentially threatening attachment related issues, the Adult Attachment Interview (AAI) allows an assessment of different strategies for regulating the attachment system. These strategies can be assessed along the 2 dimensions of security/anxiety and deactivation/hyperactivation. The greatest inferential leaps may be in characterizing strategies as deactivating. For example, individuals using deactivating strategies often report extremely positive relationships with parents, display restricted recall of attachment memories, and play down the significance of early attachment experiences. If these descriptive features are guided by a strategy that requires diverting attention from attachment information, subjects employing this strategy should experience conflict or inhibition during the Attachment Interview. In the present study, skin conductance levels were monitored for 50 college students during a baseline period and throughout the Attachment Interview. Subjects employing deactivating strategies showed marked increases in skin conductance levels from baseline to questions asking them to recall experiences of separation, rejection, and threat from parents. This finding supports the notion that individuals employing deactivating attachment strategies experience conflict or inhibition during the Attachment Interview. PMID- 1446564 TI - Reliability and validity of behavior problem checklists as measures of stable traits in low birth weight, premature preschoolers. AB - Mothers, teachers, and assistant teachers completed the Richman Behavior Checklist (BCL) at ages 2 and 3 years and the Achenbach Child Behavior Checklist for Ages 2-3 (CBCL 2-3) at 3 years for a large sample of low birth weight, premature children. Interinstrument correlations for total scores were moderate, higher for teachers and assistant teachers than for mothers, with moderate temporal stability for BCL scores. Interrater agreement for either total scores or classifications of clinically significant scores was moderately high between teachers and assistant teachers only, and children identified as disturbed by mothers versus teachers represent almost nonoverlapping groups. Furthermore, many more children were identified as disturbed using the BCL. The most powerful predictors of mothers' total CBCL 2-3 scores were HOME Inventory scores and self reported depression. The use of these scales in clinical and research contexts is discussed. PMID- 1446565 TI - Maturation of human fetal responses to vibroacoustic stimulation. AB - Maturation of human fetal response to vibroacoustic stimulation was examined in 60 fetuses from 23 to 36 weeks gestational age. Subjects received vibroacoustic or no-stimulus control trials (randomly assigned) while fetal heart rate (FHR) was recorded and movement was observed on real-time ultrasound scan. Initially, at 26-28 weeks, a small FHR deceleration response occurred; subsequently, FHR acceleration responses occurred. From 29 weeks, 83%-100% of subjects responded with an FHR acceleration > or = 10 BPM on the first vibrator trial and accelerations were observed on 83%-92% of all vibrator trials. From 26 to 36 weeks the percentage of fetuses responding with movement on the first vibrator trial increased from 58% to 100%; on all vibrator trials responses increased from 53% to 94%. It was concluded that maturation of human fetal response to vibroacoustic stimulation begins at about 26 weeks gestation, increases steadily over a 6-week period, and reaches maturity at about 32 weeks. PMID- 1446566 TI - Adult tactile stimulation during face-to-face interactions modulates five-month olds' affect and attention. AB - 3 studies were designed to investigate infant responses to tactile stimulation during brief adult-infant interaction using a modified still-face (SF) procedure. When adults pose a neutral SF expression, infants decrease gazing and smiling at the adults, and some increase grimacing, relative to normal interaction periods. This SF effect was substantially reduced in Study 1 when mothers or strangers continued to touch infants during the SF period. In Studies 2 and 3, tactile versus visual and active versus passive aspects of adult touch were isolated during different SF periods. Visible, active adult hands unaccompanied by touch elicited infant attention, but not smiling, during the SF period. By contrast, active, not passive, adult touch substantially reduced the SF effect, even when the adult's hands were invisible. In the latter condition, infants continued to gaze and smile at the adult's SF. Thus, adult facial expressions are not the only modulator of infant affect and attention during social exchanges; adult touch appears to play an active role. PMID- 1446567 TI - Developmental change in infant categorization: the perception of correlations among facial features. AB - Previous studies indicated that the ability to detect correlations among attributes emerges between 7 and 10 months of age. In the present study, the generality of this developmental transition was examined. Using an infant-control habituation procedure, 48 7- and 10-month-old infants were tested for the perception of correlations among basic facial features. The developmental effects were replicated. Only the 10-month-old infants demonstrated their sensitivity to the pattern of correlation by generalizing to a novel face that preserved the experienced pattern of correlation, while showing increased attention to a face in which the pattern of correlation was violated. 7-month-old infants generalized to both test stimuli containing familiar features, regardless of the status of the correlation. Implications for face perception and the processing of categorical information are discussed. PMID- 1446568 TI - On wooden pillows: multiple classification and children's category-based inductions. AB - Previous research has indicated that preschoolers do not distinguish between properties that are generalizable within a given category and those that are not. 2 possible general constraints on children's cognition are proposed to account for these findings. 3 studies are reported that argue against the presence of such general constraints. We examine preschoolers' understanding of the properties associated with material (e.g., wood, cotton) and object (e.g., chair, pillow) categories. In Study 1, subjects consistently made inductions based on the material compositions of items when asked to predict texture and fragility. In Study 2, the same subjects judged that items that shared material would share an unfamiliar dispositional property (e.g., gets sodden in water), but items that shared object kind would share a novel functional property (e.g., used for accelerating). Study 3 tested a younger sample of 3-year-olds and found the same sensitivity to category type, albeit with larger individual differences. By age 3, children use different modes of categorization to generalize different kinds of phenomena. These results argue against general limitations on children's abilities to use categories to make inductions. Even when children lack specific theoretical knowledge, the ability to organize phenomena into domains allows children to recognize which categories are relevant in different situations. This understanding can provide a basis for the development of more specific theories. PMID- 1446569 TI - Comparison of the attachment rates of males of the ticks Amblyomma hebraeum and A. variegatum to cattle, sheep and rabbits in the absence of aggregation attachment pheromone. AB - Losses in domestic ruminants caused by heartwater (Cowdria ruminantium infection) in Zimbabwe and Mozambique are greater when the vector is Amblyomma hebraeum than when the vector is A. variegatum. It has been suggested that the epidemiology of the disease may be influenced by the rates at which unfed adults of these two tick species attach to uninfested hosts (i.e. in the absence of the male-produced aggregation-attachment pheromone [AAP]). In this study we confined unfed males of A. hebraeum and A. variegatum on uninfested cattle, sheep and rabbits and recorded their attachment rates. Males of both species attached more rapidly on cattle than on sheep or rabbits. Males of A. hebraeum attached more rapidly than males of A. variegatum on all three host species. The differences in the attachment rates between the two species were much greater on sheep and rabbits than on cattle. The findings suggest that in the absence of AAP, pioneer males of both tick species may attach to cattle, and pioneer males of A. hebraeum may also attach to sheep. The differences in the attachment rates of A. hebraeum and A. variegatum provide a possible explanation for observed differences in the epidemiology of heartwater associated with these two vector species. PMID- 1446570 TI - The effects of nutritional status of rabbits and sheep on their resistance to the ticks Rhipicephalus evertsi evertsi and R. appendiculatus. AB - Rabbits and sheep were exposed to low- and high-protein diets and subsequently infested three times with adults of Rhipicephalus appendiculatus and Rhipicephalus evertsi evertsi. The mean weight of R.e. evertsi females which dropped from rabbits maintained on a high-protein diet decreased from 515.0 +/- 24.9 mg (naive) to 381.5 +/- 25.0 (second infestation) to 340.3 +/- 23.3 mg (third infestation) while the weight of ticks fed on animals which were exposed to a low-protein diet did not change significantly (2.7%). The mean weight of engorged females of R. appendiculatus which completed their blood meal on rabbits (high protein) decreased from 520.9 +/- 31.8 (naive) to 369.3 +/- 39 mg (3rd infestation), a significant decrease of 29.1% compared to a 12.3% decrease in weight between the 1st and 3rd infestation of females fed on animals on a low protein diet. Rhipicephalus e. evertsi fed on sheep exhibited the same phenomenon. The mean decrease in weight of 4rd-infestation ticks which dropped from sheep fed lucerne was 26.2% compared to 16.6% for ticks from sheep which were fed on grass. Hosts maintained on a low-protein diet failed to acquire resistance to ticks, lost weight and developed anaemia while those on a high protein diet developed resistance, maintained weight and did not develop anaemia. The nutritional stress of the hosts and its application in South Africa are discussed. PMID- 1446571 TI - The identification of a shared immunogen present in the salivary glands and gut of ixodid and argasid ticks. AB - The identification of a 70-kDa immunogen present in salivary gland extracts of several ixodid species, namely Hyalomma truncatum (sweating-sickness-inducing (SS+) and non-inducing (SS-) strains), Hyalomma marginatum rufipes and Rhipicephalus evertsi evertsi, is reported. The immunogen was identified by Western blots using a monoclonal antibody of the IgM isotype directed against a 70-kDa immunogen present in the salivary glands of (SS-) female H. truncatum ticks. Cross-reactivity with the gut of unfed adult ixodid ticks, Amblyomma hebraeum, Rhipicephalus simus simus, R. evertsi evertsi, Rhipicentor nuttali, H.m. rufipes, and salivary glands of adult argasid species, Ornithodoros savignyi and Ornithodoros moubata, was demonstrated using ELISA. PMID- 1446572 TI - Abnormal molecular weight profile of urinary protein in rats with streptozotocin induced diabetes. AB - A quantitative analysis of the molecular weight (MW) profile of urinary protein by SDS-PAGE was performed in streptozotocin (STZ)-injected, non-ketotic diabetic rats (DM group), diabetic rats receiving dipyridamole (DM-DIP group), normal rats (C group) and STZ-injected rats with near-normal glycemia due to insulin treatment (DM-INSULIN group). In the DM group, decrease of a small MW protein (SMWP) (MW 19.5 k) was found at 2.5 weeks, and an increase of larger MW proteins (LMWP) (MW 68 [albumin], 55 and 29 k) together with a decrease of SMWPs (MW 19.5 and 15 k) was found at 15 weeks, as compared to the C group: the MW profile of urinary protein in the DM-INSULIN and C groups was indistinguishable. At 15 weeks, creatinine clearance (Ccr) was significantly depressed and an increase in the mesangial matrix with electron dense deposits was evident in the DM group. The urinary protein abnormalities were partially corrected and the reduction of Ccr was absent in the DM-DIP group with no effect on glomerular morphology. STZ induced diabetes in rats is accompanied by a reduction of urinary SMWP, and a subsequent increase of LMWP and depression of Ccr: dipyridamole ameliorates urinary protein abnormalities and prevents the reduction of Ccr. PMID- 1446573 TI - Delayed onset and decreased incidence of diabetes in BB rats fed free radical scavengers. AB - We tested the hypothesis that free radicals play a role in the selective destruction of pancreatic beta-cells in BB/Wor rats. Diabetes-prone BB rats of both sexes and 40 days of age were divided into three groups. The control group was fed ad libitum Purina rat chow powder, while the experimental group was fed ad libitum the rat chow powder blended with a mixture of four known free radical scavengers: allopurinol, mercaptopropionylglycine, dimethylthiourea and Vitamin E. A third group was pair-fed 10 g chow powder/rat/day, since in earlier experiments we observed that rats on the experimental diet consumed only about 10 g/rat/day. All rats were studied up to age 120 days. Body weight and food intake were measured daily. Urine was tested for glucose beginning at age 60 days. When glucosuria appeared, blood glucose and urinary ketones were measured. Body weight gain in the experimental and pair-fed groups was similar, but lower than the control group. Life table analysis of the data showed a decreased and a delayed onset of diabetes in the rats fed free radical scavengers. Thus, the results of this study demonstrated that calorie restriction and the related impaired growth did not affect the incidence of diabetes in the BB rat. In addition, the results suggested a role for free radicals in the spontaneous destruction of pancreatic beta-cells in the BB rat. PMID- 1446574 TI - Presence of autoimmunity to pancreatic antigens in a patient with fibrocalculous pancreatic diabetes. AB - A case of fibrocalculous pancreatic diabetes (FCPD) is reported for which antibody and cellular immune characteristics were determined. The patient, a Thai woman, had serum islet cell antibodies (ICA) that were detected by both immunoperoxidase staining and an indirect enzyme-linked immunosorbent assay (ELISA). Serum anti-human insulin antibodies were negative by a displacement ELISA. Lymphoproliferation assay against pancreatic antigen prepared from a blood group O cadaveric donor was positive. Increased CD8+ lymphocytes were observed using direct immunofluorescence staining and flow cytometry. CD4+ T lymphocytes, B lymphocytes and NK cells were within normal levels. These findings provide evidence for autoimmunity to pancreatic antigens in a patient with fibrocalculous pancreatic diabetes. PMID- 1446575 TI - Effects of the combination of insulin and gliclazide compared with insulin alone in type 2 diabetic patients with secondary failure to oral hypoglycemic agents. AB - Twenty non-insulin-dependent diabetic patients on insulin therapy for more than 2 months due to secondary failure to oral hypoglycemic agents (OHA) were additionally treated with gliclazide, 80 mg b.i.d., for 1 month and 160 mg b.i.d. for a further 2 months, while reducing insulin dose gradually according to glycemic control. At the end of the first month, fasting blood glucose had decreased from 12.8 +/- 0.7 to 9 +/- 0.8 mM (mean +/- standard error; P < 0.005) and thereafter remained stable. Insulin requirements decreased from 34.2 +/- 2.5 to 18.3 +/- 3.2 U/day (P < 0.001). Three patients were able to cease insulin treatment altogether. A direct correlation was found between final insulin dose and previous duration of infusion monotherapy (r = 0.52; P < 0.05). C peptide/glucose score (fasting C-peptide/fasting BG x 100) increased from 0.11 +/ 0.03 to 0.21 +/- 0.05 (P < 0.05). We conclude that combined therapy reduces insulin requirement by increasing endogenous secretion, which may mainly affect hepatic glucose production as indicated by greater improvement in fasting vs. post-prandial blood glucose. This therapy could avoid hyperinsulinemia, which has been reported to be involved in macrovascular complications, and the additional haemovascular properties of gliclazide could make it more effective in such a combination. PMID- 1446576 TI - The association between clinical risk factors and outcome of diabetic foot ulcers. AB - OBJECTIVE: The aim of the study was to describe the association between clinical risk factors in diabetic patients with food ulcers in relation to outcome. DESIGN: A prospective study of 314 consecutively presenting diabetic patients with foot ulcers referred to the Department of Internal Medicine between July 1, 1983 and June 30, 1987. All patients were followed to final outcome. SETTING: All patients were treated by the same multi-disciplinary foot care team at the Department of Medicine, both as in- and out-patients. Healing was defined as intact skin for at least 6 months. RESULTS: One hundred and ninety-seven patients healed primarily, 77 after amputation, and 40 died unhealed. Signs of macroangiopathy were more common among patients who healed after amputation. The outcome was strongly related to age, though 43% of the patients with an age over 80 years healed primarily. There was no difference in smoking habits between patients who healed primarily and those who required amputation to heal. Diabetic nephropathy was found in 26% of the patients and was strongly associated with amputation. Presence of retinopathy was found in 54% of the patients, but this finding was not related to the outcome. There were no differences in short-term metabolic control as assessed by hemoglobin A1c levels between patients who healed primarily and those who healed after amputation. CONCLUSION: The presence of diabetic foot ulcers was strongly associated with age and diabetic complications such as multiple cardiovascular disease and nephropathy, which were important factors related to amputation. PMID- 1446577 TI - Outcome of gestational diabetes in Bengali Asians living in an east London health district. AB - The characteristics and outcome of pregnancy complicated by gestational glucose intolerance are described in a consecutive series of 69 Bengali Asian patients and a parallel group of 22 Caucasian patients. The Bengali patients were older and of higher parity than the Caucasians and more frequently required insulin therapy. However, the outcome of pregnancy was similar in terms of antenatal clinic attendance, the number of antenatal hospital admissions, glycaemic control, birthweight and mode of delivery. Of those patients who attended for postnatal glucose tolerance test, 20% of the Bengali population demonstrated persisting abnormality of glucose tolerance, whereas no abnormalities were evident in the Caucasian group. These findings are consistent with the high prevalence and early age of onset of non-insulin-dependent diabetes in Asian populations. The World Health Organisation (WHO) criteria for the diagnosis of impaired glucose tolerance proved insufficiently sensitive for the diagnosis of gestational diabetes. This was particularly demonstrated by four patients with apparently normal glucose tolerance by WHO criteria who subsequently required insulin therapy. PMID- 1446578 TI - Effect of disease duration on cardiac autonomic reflexes in young patients with insulin-dependent diabetes mellitus. AB - The association of disease duration with deterioration of cardiovascular autonomic reflexes was studied in two groups of young patients with insulin dependent diabetes mellitus (IDDM). The mean age of the patients in both groups was 31 years and the mean duration of the disease was 3 (n = 18) and 16 (n = 22) years. No significant difference in group means was seen in the test parameters of autonomic nerve function. However, five patients with long-term disease, but none with short-term disease, had test scores indicating cardiac autonomic neuropathy. It was concluded that (1) the duration of the disease has no overall effect on autonomic nerve function in young patients with IDDM, but (2) a few individuals with IDDM may have some precipitating factors leading to autonomic neuropathy in the course of the disease. PMID- 1446579 TI - The management of postpartum haemorrhage. PMID- 1446580 TI - CTSS: an interactive microcomputer program for the clinical screening of carpal tunnel syndrome. II. Statistical and computational aspects. AB - Details of the development and testing of a microcomputer-based statistical decision aid for screening carpal tunnel syndrome are given. The clinical and operational details have been reported in (14). PMID- 1446581 TI - Muscle conduction velocity and morphology after prolonged hypoxemia and diabetes in rats. AB - One of the electrophysiological abnormalities in the experimental rat model of chronic hypoxia (10% O2) and in the experimental rat model of diabetes is an increase in jitter in the stimulated single fibre EMG, which is thought to result from a primary disorder of the axon with its terminal branches. But muscle fibre alterations that influence the propagation of muscle action potentials can also increase jitter. The contribution of possible changes in muscle conduction velocity and muscle morphology to jitter were investigated in the present study. Muscle conduction velocities were determined and compared with the morphological properties of muscle fibers in muscles of control, chronic hypoxic and terminal stage diabetic rats. The mean muscle conduction velocities were in the same range in the three groups. The muscle fibre type composition and the mean muscle fibre diameters were about the same in the hypoxic and the control rats, whereas the muscles of the diabetic rats showed a higher percentage of intermediate type muscle fibres, which is suggestive of muscle degeneration, and a smaller mean muscle fibre diameter in comparison with muscles of the hypoxic and the control rats. It is concluded that the similarities between the electrophysiological properties of the muscles despite differences in their morphology, indicate that there is primary axonal degeneration in diabetic hypoxic rats. PMID- 1446582 TI - Automatic detection and measurement of EMG silent periods in masticatory muscles during chewing in man. AB - Silent periods are transient stops of muscle activity that are induced by mechanical or electrical stimulus. The current report describes a new algorithm which enables automatic detection and measurement of silent periods that occur in the EMG of human masticatory muscles during chewing efforts together with jaw positions in space at the occurrence of the silent periods. The EMG signal for detection of the silent period is modeled based on the observation of the EMG records induced from the jaw-closing muscles during chewing efforts in seven volunteer subjects. The algorithm for automatic detection and measurement of the EMG silent period has been applied successfully to real EMG data and the performance of the software was confirmed to be sufficiently reliable. The results of the analysis are stored in a biosignal database for possible clinical use. PMID- 1446583 TI - Subclinical neuropathy in children with inherited haemostasis disorders. AB - Motor and sensory conduction of the right peroneal and sural nerves was studied in 28 children (17 HIV seropositive) with inherited hemostasis disorders, without any symptoms of neuropathy. The amplitude ratio of the evoked muscle potential (EMP) at distal stimulation to that at proximal stimulation at the right peroneal nerve was also studied. Thirty healthy aged-matched children were used as controls. There was no statistically significant difference in the distal latency, amplitude and conduction velocity of motor and sensory nerves between patients and controls. On the contrary, a great diminution of amplitude of the EMP during proximal stimulation of nerve was observed in patients, statistically very significant, as compared to controls. This difference was independent of patients' age, severity of hemostasis defect or HIV status. In 9 patients the amplitude was within normal limits. Intraneural oozing due to trivial trauma is postulated as a possible mechanism of peroneal nerve lesion. PMID- 1446584 TI - Inadequacy of transcranial magnetic stimulation in the neurophysiologic assessment of Bell's palsy. AB - Transcranial magnetic stimulation is a non-invasive procedure which to stimulate the brain cortex and the peripheral nerve pathways. A new technique was recently introduced to record the muscle action potential of facial muscles by means of transcranial magnetic stimulation of the facial nerve. The experimental data that was obtained indicate that this technique allows to stimulate the facial nerve above the stylomastoid foramen: a greater tract of the nerve can therefore be explored than what was possible with the traditional electrical stimulation at the mastoid. Until now no comparison data was available on the clinical usefulness of the two methods. We decided to study 14 normal controls and 26 patients suffering from unilateral idiopathic facial palsy (Bell's palsy) and to submit these two groups to magnetic transcranial stimulation and electrical stimulation of the facial nerve in the mastoid region, to the purpose of observing where the nerve is stimulated by the magnetic impulse and which of the two techniques can be of accurate prognostic value in the study of the evolution of the clinical lesion. The electromyographic responses were elicited by the electrical stimulation at the mastoid and by transcranial stimulation after positioning the coil on the parieto-occipital scalp. A recording was taken from the ipsilateral orhicularis oculi muscle utilising two cupped electrodes. The latency and the amplitude of the compound muscle action potential were measured bilaterally in order to compare the results obtained on both the affected and the healthy sides. The patients were scheduled to two neurophysiological and clinical evaluations at about 30 days interval one from the other: the first test was not carried out before 20 days from the onset of the deficit; further clinical examination was carried out only 6 months later. The analysis of the results obtained in the normal controls submitted to transcranial magnetic stimulation indicate that the nerve is activated at the point where it originates from the brainstem. The study carried out showed that transcranial magnetic stimulation of the facial nerve, does not provide data which can be correlated to the clinical situation observed at the time of the study; furthermore, transcranial magnetic stimulation does not supply any prognostic data on the clinical evolution of the lesion. PMID- 1446585 TI - Cognition in homozygous beta-thalassemia disease: a multichannel auditory event related potential (P300) study. AB - Auditory Event-Related Potentials (AERP) were elicited in 25 beta-thalassemic patients, three days before and three days after a blood transfusion. The amplitude, latency and topographic distribution of P300 (P3) as well as N1, P2, N2 components were measured for the two assessment times. No significant differences in either amplitude, latency or topography were observed between the two situations, but thalassemic patients had significantly prolonged P3 latencies comparing to controls though none of them exceeded 3 standard deviations of the control mean values. Regarding P3 topography, 10 out of 25 patients showed a right centroparietal distribution area. It is concluded that information processing, as far as it is reflected in AERP components is impaired in thalassemic patients and blood transfusion have no significant influence in cognitive functions. PMID- 1446586 TI - Some conceptual remarks about supraspinal mechanisms in the control of voluntary and reflex motor activities. AB - The present paper analyses the supraspinal control of motor functions and sensorimotor integrations. Attention was paid mainly to three phenomena involved in these mechanisms: the Bereitschaftspotential, the long latency reflex responses and the short latency somatosensory evoked potentials (SEPs). The study includes the problems of long loop motor control and dyscontrol, the gating process of SEPs by movement, the role of N18 component of SEP and the analysis of supraspinal modulation of the H-reflex excitability curve in healthy subjects and in patients with some cerebral dysfunction. It was found that the amplitude of the Bereitschaftspotential increased with peripheral nerve stimulation. The experiments have shown a positive relationship between the long latency reflex latencies and the distance of the corresponding muscle from the brain. The amplitude of the long latency reflex response was found to be higher and its synchronization better in phasic movements than in a slightly sustained contraction. The short latency somatosensory evoked potentials were distinctly attenuated by movement gating. By its wide spread negativity, the N18 component probably facilitates the cortical transfer of the long latency muscle response. The H-reflex excitability curves in patients with various cerebral dysfunction exhibited a characteristic course corresponding approximately to the degree of dysfunction in focal cerebral lesions, arterial hypertension and neurasthenias. PMID- 1446587 TI - Electrophysiological findings in poliomyelitis patients at the subacute phase. AB - Electrodiagnostic tests-needle EMG, nerve conduction and somatosentory evoked potential (SEP) studies of the upper and the lower limbs were performed in three patients during the subacute phase of poliomyelitis. Although poliomyelitis is traditionally considered a "pure motor" disease, involvement of the sensory system was demonstrated by prolonged sensory nerve conduction and by delayed latencies and amplitude asymmetries of SEPs obtained from the lower limbs. Sensory deficit in poliomyelitis is well known to exist during the acute phase of illness. The present report describes the electrophysiological findings in patients during the subacute phase, several months after onset of illness. Sensory nerve action potentials and sensory evoked potentials were abnormal, especially those elicited by lower limb stimulation although the patients had no overt signs of sensory loss at that time. The associated EMG findings are described, and the probable pathologic changes of the motor unit are discussed. PMID- 1446588 TI - Sympathetic skin response in spinal cord injured patients: preliminary report. AB - Sympathetic skin responses (SSRs) were recorded in six spinal cord injured patients. These SSRs were obtained at hands and feet, after electrical stimulation of the median or the posterior tibial nerves. Below the level of the lesion, SSRs had similar latencies than normal subjects, but were more inconstant, with a lesser amplitude and elicited after stronger stimulus intensity. The origin of these somatosympathetic reflexes are discussed. SSRs recordings seem to be a simple and suitable technique for investigation of the autonomic nervous system of the spinal cord injured patients. PMID- 1446589 TI - Complete ulnar innervation of the thenar muscles combined with normal sensory fibres in a subject with no peripheral nerve lesion. AB - A complete ulnar innervation of all thenar muscles, including the opponens, have to our knowledge been described only in patients with severe traumatic lesions of the median nerve. The present study reports a subject with exclusive ulnar innervation of the thenar muscles in the right hand. The patient had no anamnestic or objective signs of peripheral nerve lesions. While his sensory and motor ulnar nerve fibres were normal, electrophysiological examination of the right median nerve showed normal course of the sensory fibres but apparently no motor fibres to the thenar muscles. PMID- 1446590 TI - The effects of acute training status on reliability of integrated electromyographic activity and "efficiency of electrical activity" during isometric contractions: a case study. AB - "Efficiency of electrical activity" (EEA) is the measure of muscular force production per unit of neuromuscular electrical activity as measured by integrated electromyographic (IEMG) activity. To determine the effects of acute training status on day-to-day and within test reliability for both IEMG activity and EEA, one experienced weight trained male was observed on three separate days (age = 33 yrs., height = 172.7 cm, body weight = 81.4 kg). The first (I) and third (III) test days were preceded by 1-2 days rest from weight training, while the second test day (II) was preceded by 4 days of rest from weight training. Two external electrodes were placed on the right biceps brachii. EMG signals were rectified by an amplifier, while a signal gain of 5000 was utilized. Three different levels of isometric muscle activity using a dumbbell, were performed at 25.0 N (2.55 kg), 87.3 N (8.90 kg), and 157.9 N (15.90 kg) of force. These resistances represented 12%, 42% and 76% respectively, of the subject's maximum capabilities. Five trials were performed at each resistance on each of the test days. Repeated measures ANOVAs (3 x 3) were used to determine differences between test days and loads (p < or = 0.05). Within day variations were determined by coefficient of variation (CV = SD/mean x 100%). The EEA for each test day was curvilinear, with greater forces exhibiting lower EEA. Test day II exhibited the greatest EEA, which may have been related to the acute training status of the subject.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446591 TI - The parallel and the common k-NN rules for an analysis of electromyograms in spinal muscular atrophy of childhood. PMID- 1446592 TI - Tumor necrosis factor-alpha induces clustering in ovarian theca-interstitial cells in vitro. AB - Tumor necrosis factor-alpha (TNF) has been implicated in the regulation of steroidogenesis in theca-interstitial cells (TIC). The purpose of this study was to evaluate any change in TIC morphology during the time course of TNF-induced inhibition of LH-stimulated androstenedione production. Ovaries from immature hypophysectomized rats were enzymatically digested and highly purified TIC were obtained by density gradient centrifugation. TIC treated with TNF (0.1-10 ng/ml) demonstrated distinct clustering in the presence and absence of LH (50 ng/ml). The number of clusters and the mean area per cluster were greatest after 4 days as a result of treatment with 1 or 10 ng TNF/ml. In addition, a dose-dependent inhibition of LH-supported androstenedione production was induced by TNF. TNF also inhibited LH-induced androstenedione in TIC after 2, 4, or 6 days of continuous LH treatment, and TIC clustering still occurred. TIC clustering was impeded by the protein kinase inhibitor H7 at 10 microM; however, the protein kinase inhibitor, HA 1004 (5 microM), did not inhibit TNF-induced clustering in TIC. Since H7 blocked TNF induced clustering, but did not block TNF inhibition of LH stimulated androstenedione synthesis, it is suggested that alternate signal transduction pathways for TNF induced inhibition of LH-stimulated androstenedione and stimulation of clustering of TIC may exist. The results also indicate that the TNF-induced TIC clustering may be independent of the TNF-induced inhibition of LH-stimulated androstenedione production and states of LH-induced differentiation of TIC. PMID- 1446593 TI - Enhanced stimulation of follicle maturation and ovulatory potential by long acting follicle-stimulating hormone agonists with extended carboxyl-terminal peptides. AB - The induction of granulosa cell differentiation and follicle maturation is dependent upon the stimulatory actions of FSH. Our recent studies used recombinant DNA technology to fuse the carboxyl-terminal peptide (CTP) of hCG beta-subunit to the carboxyl-terminus of the FSH beta-subunit. The resulting FSH analog has identical in vitro receptor-binding and biological activities as wild type FSH (WT-FSH), but an increased circulating half-life. The present studies examined further the ability of FSH with one (FSH-CTP1) or two (FSH-CTP2) appended CTPs to promote granulosa cell differentiation and follicle ovulatory potential. WT-FSH, FSH-CTP1, and FSH-CTP2 were produced from Chinese hamster ovary cells transfected with the common alpha-subunit and respective beta subunit. Hormone concentrations were quantitated by RIA, and relative levels confirmed by radioligand receptor assay. Both FSH-CTP1 and FSH-CTP2 retained full FSH receptor-binding activity, but did not bind LH receptors. To compare in vivo bioactivity, immature estrogen-primed female rats received ip injections of FSH or the agonists at 0 and 24 h. At 48 h, substantial stimulation (up to 2.5-fold) of ovarian weight was induced by 1.0 and 3.0 IU/day FSH-CTP1 or FSH-CTP2, whereas a higher dose (10 IU/day) of WT-FSH was required for an 1.8-fold stimulation. Although the in vivo potencies of FSH-CTP1 and FSH-CTP2 were similar, FSH-CTPs were about 10-fold more potent than WT-FSH in inducing granulosa cell aromatase activity and LH receptors. We further reduced the frequency of hormone administration. Increasing doses (1-10 IU) of a single ip injection of FSH-CTP1 resulted in dose-dependent increases in granulosa cell aromatase activity and LH receptor content 48 h later. Although a single injection (10 IU) of WT-FSH had no effect, the same total dose of WT-FSH administered as four 2.5-IU injections 12 h apart was effective. To test the ovulatory potential of ovarian follicles, rats received a single injection of FSH-CTP1, followed 52 h later by 5 IU hCG to induce ovulation. Although hCG did not induce ovulation in females receiving a single dose (10 IU) of WT-FSH, 20 +/- 2 and 43 +/- 5 ovulated ova/rat were found in animals primed with 3 and 10 IU FSH-CTP1, respectively. Because twice daily injections of WT-FSH (2.5 IU/injection) also increased the ovulatory potential of the ovary, the enhanced effectiveness of FSH-CTP1 appears to be related to its increased circulating half-life.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446594 TI - A radioimmunoassay of rat type I iodothyronine 5'-monodeiodinase. AB - A highly sensitive, specific, and reproducible RIA has been developed to measure rat type I iodothyronine 5'-monodeiodinase (5'-MD). A 16-amino acid peptide (LAP 744) corresponding to a portion of the carboxy-terminal region of the rat liver 5'-MD, as predicted from its cDNA, was synthesized, and rabbits were immunized with the peptide-BSA conjugate. In a final dilution of 1:15,000, our anti-5'-MD antibody bound about 30-35% of a tracer amount of [125I]LAP-744. The detection threshold of the RIA approximated 0.08 pmol LAP-744 or an equivalent amount of 0.08 pmol 5'-MD. Rat liver and kidney microsomes produced dose-response curves that were essentially parallel to that of LAP-744. No inhibition of binding of [125I]LAP-744 to antibody was produced by 0.3 mg or less rat microsomal proteins from testes, heart, brain, muscle, spleen, intestine, lung, placenta, or fetal liver. Recovery of nonradioactive LAP-744 added to spleen microsomes averaged 103%. The coefficient of variation averaged 4% within an assay and 11% between assays. In 16 normal rats studied, the mean (+/- SD) 5'-MD content was 2.4 +/- 0.22 pmol/mg protein in liver microsomes and 2.5 +/- 0.27 pmol/mg protein in kidney microsomes. Fasting of the rat for 2-4 days was associated with a significant reduction in both the activity and the content of the 5'-MD in liver and kidney. Hypothyroidism was also associated with a significant decrease in the activity and content of 5'-MD in both tissues. Significant opposite changes were observed in these parameters in hyperthyroidism. Treatment of the rat with sodium ipodate for 3 days was associated with a significant decrease in both the activity and the content of 5'-MD in liver and kidney. A similar treatment of the rat with propylthiouracil induced a clear reduction in the activity of 5'-MD in liver and kidney, but the content of the enzyme was significantly increased in both tissues. Rats treated with aurothioglucose for 3 days exhibited a significant decrease in 5'-MD activity in liver and kidney microsomes, whereas the tissue content of 5'-MD was not affected. A similar treatment of the rat with methimazole had no significant effect on either the activity or the content of 5' MD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446595 TI - Distribution of cholecystokinin forms in intestinal secretory granule subtypes. AB - Peptides and proteins destined to be released in response to stimuli are found in the regulated secretory pathway. Substances in this pathway are packaged into secretory granules, wherein they are often rendered osmotically inactive by complexing to an oppositely charged molecule. The complexing mechanism employed by members of the cholecystokinin (CCK) peptide family is unknown, but the heterogenous charges of CCK peptides makes it possible that different CCK peptides have different abilities to form intragranular complexes. If the number of osmotically active intragranular CCK peptides varies, corresponding variations in secretory granule density should result, and when intestinal CCK secretory granules were purified on isotonic density gradients, four granule peaks were observed. Granules containing greater proportions of short CCK forms tended to have the lowest buoyant densities, suggesting that they contain a greater number of osmotically active molecules than granules of lower density and that short or all intragranular CCK forms are osmotically active. CCK secretory granules also contained novel CCK forms; in addition to previously characterized forms, granules contained a CCK form that appears to be CCK-6 and a form that could arise from cleavage of CCK-58 at position 4, 10, or 12. Because intragranular enzymes are responsible for peptide posttranslational processing, the intragranular CCK forms observed in the present study are likely to be authentic CCK-processing products. Finally, CCK sorting in intestine apparently differs from that in a rat medullary thyroid carcinoma cell line, in which CCK-22 and CCK 33 are not found in the regulated secretory pathway. PMID- 1446596 TI - Reduction of alpha-naphthylisothiocyanate-induced hepatotoxicity by recombinant human hepatocyte growth factor. AB - Hepatocyte growth factor (HGF) is a potent stimulator of DNA synthesis in cultured hepatocytes. To determine whether HGF has any activity in vivo, we have tested HGF in rats in which intrahepatic cholestasis was induced by acute administration of alpha-naphthylisothiocyanate (ANIT). The hepatotoxic effects of a single injection of ANIT were manifested 48 h later as large increases in serum bilirubin, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. These biochemical changes were accompanied by widespread periportal edema, hypertrophy of bile duct epithelium, and randomly scattered areas of liquifaction necrosis in the hepatic parenchyma. The increases in bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were markedly attenuated when HGF was administered 30 min before ANIT and again at 6, 12, 24, 30, and 36 h after ANIT. In addition, this HGF dosing regimen completely prevented the occurrence of parenchymal lesions, although it had no effect on periportal histopathology. The effect of ANIT was dose dependent; a maximal response was observed at 320 micrograms/kg per injection, with an intermediate response at 105 micrograms/kg. Delaying the administration of HGF until 12 h after ANIT was as effective as when administration was begun 30 min before ANIT. Taken together these results show that HGF can prevent some aspects of ANIT hepatotoxicity. PMID- 1446597 TI - Paracrine regulation of adipose differentiation by arachidonate metabolites: prostaglandin F2 alpha inhibits early and late markers of differentiation in the adipogenic cell line 1246. AB - The effect of arachidonate metabolites on the differentiation of the adipogenic cell line 1246 was investigated. Among the metabolites examined, only prostaglandin F2 alpha (PGF2 alpha) inhibited differentiation in a dose-dependent fashion with an ED50 of 3 x 10(-9) M. PGF2 alpha inhibited the mRNA expression of lipoprotein lipase, clone 154, and fatty acid-binding protein, which are early markers of differentiation, as well as glycerol-3-phosphate dehydrogenase specific activity and triglyceride accumulation, which are late markers of differentiation. Chronic exposure of 1246 cells to PGF2 alpha before and during differentiation indicated that the cells that have just initiated their differentiation program were the most susceptible to the inhibitory effect of PGF2 alpha. Since 1246 cells produce PGs, we determined whether the PG produced by the cells influenced adipose differentiation. Cyclooxygenase inhibitors added to the culture medium stimulated differentiation of 1246 cells up to 18-fold depending on the type and concentration of inhibitor used. In contrast, lipoxygenase inhibitors had no effect. Treatment of 1246 cells with arachidonic acid resulted in a dose-dependent inhibition of cell differentiation. Oleate or linoleate had no effect. These data indicate that PGF2 alpha inhibits early and late events of adipose differentiation and that the endogenous production of PGs (particularly PGF2 alpha) plays an important role as a negative paracrine or autocrine regulatory pathway of adipose differentiation. PMID- 1446598 TI - Phorbol ester activation of the protein kinase C pathway inhibits gonadotropin releasing hormone gene expression. AB - The effects of the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA), an activator of protein kinase C (PKC), and the PKC inhibitor staurosporine on GnRH secretion and mRNA levels were studied in GT1-7 hypothalamic neuronal cells. Dose response and time-course studies revealed that TPA (10(-8) M) acutely increased GnRH secretion 3-fold at 3-6 h, which then declined to baseline at 24 h, while it progressively decreased GnRH mRNA levels by 50% and 70% at 6 and 24 h, respectively. To ensure that these effects were due to activation and not down regulation of PKC, cells were treated for 30 min with TPA (10(-8) M). This brief exposure to TPA also resulted in a decrease (60%) in GnRH mRNA levels at 6 h, with a 1.5- to 2-fold increase in GnRH secretion compared to control values, suggesting that activation of PKC decreases the pretranslational expression of GnRH while increasing GnRH secretion. Additional studies measured PKC activity and documented a shift from a cytosolic to a membrane fraction after incubation with TPA, again supporting PKC activation. Exposure of GT1-7 cells to staurosporine (10(-8) M), a PKC inhibitor, resulted in no change in the level of GnRH mRNA or secretion at 6 h. However, incubation with both TPA and staurosporine prevented the decrease in GnRH mRNA levels and partially blocked the increase in GnRH secretion induced by TPA. We conclude that TPA, by activating the PKC pathway, acutely increases GnRH secretion, but dramatically decreases GnRH gene expression. The exact mechanism of these divergent effects on the synthesis and secretion of GnRH remain to be elucidated. PMID- 1446599 TI - Ontogeny of hepatic nuclear triiodothyronine receptor isoforms in the rat. AB - We have determined the contribution of the thyroid hormone receptor (TR) isoforms TR alpha 1 and TR beta 1 to the postnatal rise in rat hepatic nuclear T3-binding capacity. In agreement with previous studies, total hepatic nuclear binding capacity rose by about 8-fold from the 19th day of gestation to young adulthood at 2 months of age (0.10 +/- 0.03 to 0.86 +/- 0.17 pmol/mg DNA). The levels of specific TR species were measured by immunoprecipitation of T3-binding activity from hepatic extracts using a panel of antisera directed against specific regions of the TR isoforms. The difference between receptor immunoprecipitated with antibody against TR beta 1 and that precipitated with an antibody against an identical region in both TR beta 1 and TR alpha 1 was tentatively assumed to represent TR alpha 1. TR alpha 1 accounted for virtually all T3-binding activity in fetal liver on gestational day 19 (G19), increased by 2-fold shortly after birth, and remained constant thereafter. TR alpha 1 mRNA, on the other hand, was highest in concentration on G16 and fell by 50-75% in the adult. TR beta 1 was undetectable by immunoprecipitation of hepatic extracts from fetuses on G19. However, Northern analysis showed the presence of TR beta 1 mRNA in the fetal liver, which rose in concentration by 3- to 4-fold in late gestation and then remained constant. The contribution of TR beta 1 to total binding capacity rose to 33% and 40% on postnatal days 15 and 30, respectively, and to 80% in the adult liver. Immunohistochemical analyses of hepatic sections confirmed the presence of very low levels of TR beta 1 in fetal liver as early as G16 and G19, and a sharp rise in TR beta 1 protein concentration in the postnatal period. This indicated that the increase in TR beta 1-binding capacity results from increased TR beta 1 mass. The increase in TR beta 1-binding capacity, thus, is due to increased translational efficiency of the beta 1 mRNA or stabilization of the TR beta 1 protein. The prominence of TR alpha 1 in both rat fetal liver and fetal brain, as previously demonstrated in our laboratory, raises the possibility that this receptor isoform may carry out specialized functions in the fetus and that TR beta 1 subserves still other functions at later stages of development.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446600 TI - Mouse uterine stromal cells secrete a 30-kilodalton protein in response to coculture with uterine epithelial cells. AB - While uterine stromal cells (USC) appear to modify the function of uterine epithelial cells (UEC) under certain conditions in vivo, relatively little is known about the effect of epithelial cells on stromal cell differentiation and function. To determine if UEC modulate USC function in vitro, highly enriched (> 95%) cultures of polarized UEC were first cultured on Matrigel-coated filters in serum-free medium until confluent, then cocultured with USC for up to 120 h. Subsequently, while maintaining both cell types in physically separate compartments, filters containing UEC were removed, and USC phenotypic markers assayed. Coculture with UEC did not affect the expression of two markers of USC differentiation (desmin and laminin), USC DNA content, [35S]methionine uptake, or total protein synthesis or secretion. However, coculture of USC with UEC or medium conditioned by UEC induced the secretion of a 30-kilodalton protein (p30) from USC as early as 24 h of coculture and through 120 h of coculture. In addition, secretion of a 60-kilodalton protein by USC was frequently observed in response to coculture with UEC. Neither the hormonal stage from which uterine cells were recovered, nor the addition of exogenous progesterone or estradiol modulated UEC-induced p30 secretion. Several purified growth factors (transforming growth factor-beta, epidermal growth factor, interleukin-1 alpha, and fibroblast growth factor) added to the serum-free culture medium failed to induce p30 secretion by USC. The p30-inducing activity in UEC-conditioned medium could not be abolished by either heat or trypsin treatment, suggesting that it is not a protein. Purified prostaglandin E2 or F2 alpha or platelet-activating factor did not induce p30 secretion by isolated USC. Of several epithelial and fibroblastic cell lines tested, UEC and a human uterine adenocarcinoma cell line (RL95-2) were the most effective in inducing p30 secretion by USC. Moreover, UEC also were able to modulate protein secretion by nonuterine murine fibroblast cell lines. Collectively, these data demonstrate that UEC can modulate USC function in vitro via a soluble factor(s). PMID- 1446601 TI - Pituitary extract causes aggregation and differentiation of rat mammary tumor MTW9/Pl cells. AB - Alkaline pituitary extracts (PE) of the mammosomatotropic tumor MtTW10 differentiated cultured PRL-independent rat mammary tumor cells MTW9/Pl. Within 24 h, MTW9 cells growing in suspension began to aggregate and adhere to the plastic dish. Cultured dispersed MTW9 cells were undifferentiated, but PE treatment resulted in organoid aggregates that exhibited glandular luminal structures and periodic acid-Schiff-positive material consistent with basement membrane formation. Morphometric examination of organoids demonstrated a reduction in nuclear and cell perimeters compared to those of untreated cells. Electron microscopy showed that the treatment resulted in polarization, nuclear changes, junctional complexes, secretory spaces, microvilli, and basement membrane formation. A disaggregated undifferentiated tumor now appeared as a differentiated adenocarcinoma. PE induced expression of laminin and milk protein, but failed to increase fibronectin expression. Extracts of MTOM (a variant of MtTW10 which secretes little PRL) and bovine pituitary also produced aggregation and adhesion of MTW9. A number of tissue extracts, growth factors, and hormones failed to produce such aggregation. Laminin, but not fibronectin, produced aggregation and adhesion similar to those produced by PE. Cycloheximide inhibited the aggregation effect of PE, but not that of laminin. PE was mitogenic for MTW9, but inhibition of proliferation by vinblastine did not inhibit the aggregation induced by PE. These observations suggest that the pituitary contains a novel factor that stimulates matrix synthesis, resulting in differentiation, possibly laminin induced. PMID- 1446602 TI - Specificity of steroid binding in New World primate B95-8 cells with a vitamin D resistant phenotype. AB - We recently described the existence of a competitive binding component in vitamin D-resistant New World primate cells that has a relatively low affinity (Kd, approximately 10(-8) M) but high capacity for 1,25-dihydroxyvitamin D3 [1,25 (OH)2D3] compared to that possessed by the vitamin D receptor (VDR). Here we show that this binding component is capable of binding a vitamin D3 metabolite other than 1,25-(OH)2D3 as well as steroid hormones structurally disparate from vitamin D3 sterols. We studied the binding of [3H]1,25-(OH)2D3 and [3H]25-hydroxyvitamin D3 ([3H]25OHD3) in extracts of the vitamin D-resistant marmoset lymphoblastic cell line B95-8 in the presence and absence of potential competitive ligands, including 25OHD3, 1,25-(OH)2D3, 17 beta-estradiol, testosterone, and progesterone, at concentrations ranging from 1-100 nM. Compared to extracts containing the authentic VDR, extracts of B95-8 cells bound 180% more 1,25 (OH)2D3 and 12-fold more 25OHD3 on a weight basis. The affinity of this binder for 25OHD3 was 2.2 times as great as its affinity for 1,25-(OH)2D3. Further, at concentrations approaching the Kd of this binder for 1,25-(OH)2D3, 25OHD3 was 3 times more effective than 1,25-(OH)2D3 in competing with [3H]1,25-(OH)2D3 for binding. This binder eluted from a Sephadex G-100 column with an apparent mol wt of 58 kilodaltons, and pooled elution fractions from the column encompassing this mol wt range were capable of inhibiting binding of 1,25-(OH)2D3 to the VDR by 65%. Competitive steroid binding analyses showed estradiol to be at least as effective as 1,25-(OH)2D3 in inhibition of [3H]1,25-(OH)2D3 binding; homologous binding studies with 17 beta-estradiol as labeled and competitive ligand demonstrated that concentrations of the gonadal steroid that successfully displaced [3H]1,25-(OH)2D3 also displaced 17 beta-[3H] estradiol. Using [3H]25OHD3 as the labeled ligand and a more extensive array of competitive ligands, the rank order of steroid binding was 25OHD3 > 1,25-(OH)2D3 > or = estradiol = progesterone = testosterone. These results suggest that the phenotype of steroid hormone resistance in New World primates may result from the overexpression of an intracellular 58-kilodalton protein(s) that interferes with the steroid-receptor interaction by competing for ligand binding. PMID- 1446603 TI - Analysis of pulsatile secretion of thyrotropin and growth hormone in the hypothyroid rat. AB - To characterize the role of TRH in the generation of TSH pulsatility as well as the effect of hypothyroidism on episodic GH secretion, blood was constantly withdrawn (30-60 microliters/min) from rats treated with 0.02% methimazole in the drinking water for 8-10 days. This treatment significantly reduced circulating levels of both T3 and T4 and elevated plasma TSH; however, since thyroid hormone titers were still detectable (T3, 39.6 +/- 5.3 vs. 89.8 +/- 5.3 ng/dl in euthyroid animals), methimazole-treated rats were referred to as being mildly hypothyroid. TSH was found to be secreted in secretory bursts, consisting of one to several peaks in these rats. Pulsar analysis of TSH secretory profiles revealed a mean pulse frequency of 2.8 pulses/h, a mean pulse amplitude of 10 ng/pulse, and a mean pulse duration of 0.2 h. Euthyroid rats exhibited similar fluctuations of circulating TSH levels; however, due to the variability of the TSH RIA in the range of euthyroid TSH titers, no significant pulsatility was detected by Pulsar. Mean plasma TSH levels in eu- and hypothyroid rats were 2.3 +/- 0.3 and 14.6 +/- 1.8 ng/ml, respectively. To confirm that the TRH antiserum (TRH-AS) used in the present study for passive immunization had sufficient binding capacity to absorb endogenous TRH release, euthyroid rats were pretreated with either normal rabbit serum or TRH-AS, followed by the injection of clonidine (100 micrograms/kg BW, iv). This alpha 2-adrenergic agonist caused a significant (P < 0.01) 12.7-fold rise in plasma TSH levels in normal rabbit serum-treated animals, which was completely abolished by TRH-AS pretreatment, indicating that clonidine stimulates TSH secretion via activation of hypothalamic TRH release. When TRH-AS was slowly infused into hypothyroid rats that were sampled frequently for the detection of TSH pulsatility, it caused a significant (60.3%; P < 0.01) decrease in mean TSH levels, with TSH titers approaching euthyroid concentrations 1 h after the infusion of TRH-AS. The antiserum treatment also caused the disappearance of statistically significant (Pulsar) TSH secretory pulses. Mild hypothyroidism shifted the GH secretory profiles from a low frequency, high amplitude in euthyroid animals to a high frequency, low amplitude pattern in hypothyroid rats. Mean GH levels in hypothyroid rats were 76% lower than those in euthyroid controls. These findings show that TSH is secreted in a pulsatile fashion in the hypothyroid rat and that TRH is predominantly responsible for the generation of TSH pulsatility.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446604 TI - Correlation of follicle-stimulating hormone (FSH)-receptor complex internalization with the sustained phase of FSH-induced calcium uptake by cultured rat Sertoli cells. AB - We have previously reported that synthetic peptide amides corresponding to regions of the beta-subunit of human FSH [hFSH-beta-(1-15) and hFSH-beta-(51-65)] have the ability to bind calcium and to facilitate its entry into liposomes. In the present study, we have examined the ability of synthetic peptides corresponding to the entire primary structure of hFSH-beta-subunit, to induce calcium influx in cultured rat Sertoli cells. Calcium (as 45Ca2+) uptake in response to 50 microM hFSH-beta-(1-15), hFSH-beta-(21-35), or hFSH-beta-(51-65) peptide amides was 2.5-, 2.4-, and 2.0-fold higher, respectively, than basal uptake. Pretreatment of Sertoli cells for 5 min with phenylarsine oxide (PAO, 80 microM), an inhibitor of receptor-mediated endocytosis, significantly (P < 0.05) reduced 45Ca2+ influx in response to hFSH-beta-(1-15), hFSH-beta-(21-35), and hFSH-beta-(51-65). A delay of 20 min was required, however, before the inhibitory effect of PAO on 45Ca2+ uptake was observed. Specific binding of [125I] hFSH to receptor at 4 C was unaffected by PAO. After 2 h at 37 C, however, approximately 1.6-fold more [125I]hFSH specifically bound at 4 C could be dissociated from the cell surfaces of PAO-pretreated Sertoli cell monolayers, compared to untreated monolayers. This result is consistent with an inhibitory effect of PAO on FSH receptor internalization. Chloroquine (at 100 microM), a lysosomotropic agent known to block FSH degradation, also significantly (P < 0.05) inhibited FSH induced 45Ca2+ uptake. Extending our earlier studies, these results suggest that the sustained (> 20 min) phase of FSH-induced calcium uptake, also seen in response to synthetic hFSH-beta-(1-15), hFSH-beta-(21-35), and hFSH-beta-(51-65) peptide amides, may occur as a consequence of FSH-receptor complex internalization and FSH degradation. Vesicular uptake of extracellular calcium, which accompanies internalization of FSH-receptor complexes, and release of channel-forming peptides by lysosomal hydrolysis of FSH suggests a novel mechanism whereby FSH increases intracellular calcium levels in Sertoli cells. PMID- 1446605 TI - Individual parathyroid cells exhibit cyclic secretion of parathyroid hormone and chromogranin-A (as measured by a novel sequential hemolytic plaque assay). AB - PTH and chromogranin-A (CgA) are the two major proteins secreted from the parathyroid gland. We investigated the secretory patterns of CgA and PTH using a sequential reverse hemolytic plaque assay (RHPA). The RHPA allows detection of hormone secretion from individual cells after a secretory stimulus. For the sequential RHPA, bovine parathyroid cells were mixed with protein-A-conjugated ovine erythrocytes (oRBC). Antiserum, either anti-PTH or anti-CgA, was added under optimal secretory conditions. The addition of complement caused lysis of oRBC surrounding hormone-secreting cells. In this stage (stage 1), individual cells were identified and indexed as secreting or nonsecreting cells. For stage 2, a new lawn of oRBC was established, and a second RHPA was performed on the same population of cells, allowing for the detection of secretory patterns. In the single stage RHPA, about three fourths of the cells formed CgA plaques compared to only about half that formed PTH plaques, suggesting that CgA and PTH are not always cosecreted. In the sequential RHPA, of the cells that did not secrete CgA or PTH in stage 1, up to half secreted in stage 2. Of those cells that secreted in stage 1, up to one fourth did not secrete in stage 2. These results indicate that the parathyroid cells "cycled" between secretory and nonsecretory phases. Our experimental design precluded our obtaining unequivocal data on whether CgA is an autocrine/paracrine regulator of PTH secretion. PMID- 1446606 TI - Calbindin-D9K gene expression in the lung of the rat. Absence of regulation by 1,25-dihydroxyvitamin D3 and estrogen. AB - Calbindin-D9K (CaBP9K) is classically considered to be the molecular expression of 1,25-dihydroxyvitamin D3. The hormone is known to regulate the rat CaBP9K gene in duodenal tissue at transcriptional and posttranscriptional levels. This study shows that the CaBP9K gene is expressed in the rat lung, and that this expression is probably not vitamin D- or estrogen-dependent. The CaBP9K gene is not expressed in alveolar macrophages, but CaBP9K messenger RNA (mRNA) was localized by in situ hybridization in alveolar epithelial cells. CaBP9K mRNA was detected as early as the 20th day of gestation. The quantity of CaBP9K mRNA gradually increased during growth, from 1-77 days after birth, whereas the CaBP9K concentration dramatically increased from day 19 to day 20 of gestation. Vitamin D-deficient male rats (8 weeks old) were given a single injection of 1,25 dihydroxyvitamin D3 (650 pmol/100 g body wt) and killed 1 h and 24 h after injection. The hormonal treatment resulted in a rise in duodenal CaBP9K mRNA, but no significant change in lung extracted CaBP9K mRNA. Mature ovariectomized rats were injected with 17 beta-estradiol (0.5 microgram/100 g body wt) and killed 24, 48, and 72 h later. The CaBP9K mRNA concentration in the uterus was markedly dependent on estrogen; that of the lung was not. The factors regulating the CaBP9K gene expression in the lung remain to be determined. PMID- 1446607 TI - A cryptic peptide (160-169) of thyrotropin-releasing hormone prohormone demonstrates biological activity in vivo and in vitro. AB - TRH is synthesized as a precursor peptide containing five copies of the sequence Gln-His-Pro-Gly, QHPG, flanked by paired basic amino acids, and linked by other peptides. We tested one cryptic peptide, PPT (160-169, SFPWMESDVT), as a possible physiological regulator of pituitary activity in vivo. Male rats were cannulated (jugular) and received a single dose of either PPT or TRH (10(-8)-10(-6) M). PPT caused no consistent effects on either TSH or PRL secretion, while TRH stimulated the secretion of both hormones. However, PPT stimulated a dose-dependent increase in both pituitary TSH beta and PRL mRNA content at 240 min similar to TRH. In primary cultures of rat pituitaries, PPT stimulated a maximum 4-fold increase in TSH beta mRNA and a 2-fold increase in PRL mRNA in 4 h, while TRH increased both TSH beta and PRL mRNA approximately 3-fold. Again, PPT had no significant effect on TSH or PRL secretion into the medium. Thus, PPT appears to be a physiological regulator of both TSH and PRL synthesis, but, unlike TRH, does not act as a secretagogue. PMID- 1446608 TI - Androgens lower prostaglandin E2 levels in neonatal mouse bulbourethral gland in in vitro cultures. AB - The neonatal mouse bulbourethral gland (BUG) in vitro culture model is useful to study hormone-induced genitourinary (GU) tract growth and differentiation. Like the prostate, the BUG is a derivative of the urogenital sinus and may have relevance to understanding growth processes involved in normal and pathological GU tract development. Previous studies have reported androgen-induced elevation of prostaglandin E2 (PgE2) levels in mouse GU tract in vivo. PgE2 has been proposed to mediate neonatal GU tract masculinization. In our studies, tissues were obtained from neonatal male mice and cultured in serum-free Dulbecco's Modified Eagle's Medium-Ham's F-12 Medium (1:1) supplemented with varying concentrations of androgen. PgE2 levels were measured by RIA in the medium, and tissue specimens were cultured for 7 days or less. During this period, androgens induced proliferation and glandular morphogenesis in the BUGs. In the absence of androgen, tissue and medium PgE2 levels increased over 7 days. Significant (P < 0.05) PgE2 increases over day 1 control values were observed from days 5-7 in tissues and on day 7 in media. During this same time period, androgen supplementation decreased PgE2 levels. Significant (P < 0.05) PgE2 decreases from day 1 cultures were observed from days 3-7 in tissues and on day 7 in media. PgE2 was decreased significantly (P < 0.05) by androgen compared to control values from days 3-7 in tissues and from days 5-7 in media. On day 7 of culture, PgE2 levels were significantly (P < 0.05) inhibited by androgen in a concentration dependent fashion in tissues and media. Maximal androgen-induced inhibition of PgE2 levels was 96% and 99% in tissues and media, respectively. Although the addition of indomethacin to control cultures markedly inhibited PgE2 production, BUG morphology was unaffected. In addition, the morphology of androgen-stimulated BUGs does not appear to be affected by the addition of exogenous PgE2. We conclude that although androgens induce development and decrease PgE2 levels, PgE2 does not appear to play a major role in in vitro BUG postnatal growth and morphogenesis. The BUG in vitro culture model may mimic growth and morphogenetic processes occurring in the human GU tract. Further understanding of the role of steroid hormones and PG metabolism may yield additional insight into developmental and proliferative GU tract disorders. PMID- 1446609 TI - Central hypothyroidism is associated with advanced age in male Fischer 344/N rats: in vivo and in vitro studies. AB - We investigated age-related alterations in hypothalamic-pituitary-thyroid function in a series of in vivo and in vitro studies in 2-, 8-, 18-, and 24-month old male Fischer 344/N (F344/N) rats. Thyroid histology showed progressive follicular loss with advancing age; this was associated with significant and progressive decrements in plasma levels of free T4 and free T3, but not immunoreactive TSH, which remained unchanged with age. This was accompanied by a progressive age-dependent loss in in vivo responsivity of the thyrotroph to synthetic TRH and a paradoxically augmented response of GH to this peptide in the oldest rats. Steady state levels of prepro-TRH mRNA in the hypothalamic paraventricular nucleus were decreased with age, whereas TRH content in and in vitro secretion by whole hypothalami remained unchanged. Both anterior pituitary steady state TSH beta-subunit mRNA levels and TSH content were decreased with age. Taken together, these data suggest that aging in male F344/N rats is associated with a progressive, centrally mediated decrease in thyroid function. The relative contributions to this phenomenon of age-related alterations in supra hypothalamic and/or hypothalamic vs. pituitary thyrotropic function remain to be determined, as do the relationships between changes in hypothalamic-pituitary thyroid function and those in aging per se. PMID- 1446610 TI - Effects of luteinizing hormone on glucose metabolism in cumulus-enclosed bovine oocytes matured in vitro. AB - The effects of LH on glucose metabolism within cumulus cell-enclosed bovine oocytes were determined. Cumulus cell-enclosed bovine oocytes were matured in vitro (IVM) in control medium alone or supplemented with LH, FSH, or TSH, then individually assayed for the metabolism of D-[5-3H]glucose, D-[1-14C]glucose, D [6-14C]glucose, and D-[U-14C]glucose. Glycolytic activity was unchanged after IVM in 1 microgram LH/ml, but was greater (P < 0.05) after culture in 10 and 50 micrograms LH/ml than the control value (1.34 +/- 0.13, 1.87 +/- 0.20, and 1.63 +/- 0.14 vs. 1.19 +/- 0.13 nmol 3H2O/micrograms protein.3 h, respectively). Increased glycolytic activity was observed within cumulus cell-enclosed oocytes, but not in cumulus cell complexes from which the oocyte was removed. Also, no glycolysis was detected when denuded oocytes from any IVM treatment were assayed. Glycolytic activity was greater (P < 0.01) after IVM in LH (10 micrograms/ml) vs. TSH (0.5 microgram/ml), FSH (1.0 micrograms/ml), and control treatments (3.04 +/- 0.10, 2.44 +/- 0.10, 2.33 +/- 0.10, and 2.13 +/- 0.10 nmol 3H2O/micrograms protein.3 h, respectively). Treatment with TSH also increased (P < 0.05) glycolytic activity compared to control values. Relative to control values after IVM, pentose cycle activity was 73.6% less, 2.9% higher, and 33.9% higher with LH, FSH, and TSH treatments, respectively. Total 14CO2 generated from D-[U 14C]glucose did not differ between treatments. Glucose oxidation by the pentose cycle accounted for 30.5%, 29.7%, 40.7%, and 11.1% of the total 14CO2 production after IVM in control medium, FSH, TSH, or LH, respectively. Data indicate that IVM with LH results in increased glycolytic activity and mitochondrial glucose oxidation within cumulus cell-enclosed bovine oocytes, and that this may represent a mechanism by which LH enhances oocyte maturation. PMID- 1446611 TI - Glutamic acid decarboxylase messenger ribonucleic acid is regulated by estradiol and progesterone in the hippocampus. AB - Ovarian steroids modulate learning, memory, and epileptic seizure activity, functions that are mediated in part by the hippocampus. Normal function depends on precise interactions between the inhibitory gamma-aminobutyric acid (GABA)ergic and excitatory glutamatergic neurons of the hippocampus. To determine whether estradiol and progesterone interact with GABAergic neurons, the levels of mRNA for glutamic acid decarboxylase (GAD), the rate-limiting enzyme for GABA synthesis, were measured by in situ hybridization histochemistry with 35S-labeled riboprobes complimentary to the feline GAD cDNA. The levels of mRNA for GAD were analyzed in selected region of the dorsal hippocampus and medial basal hypothalamus in ovariectomized, ovariectomized estradiol-treated, and ovariectomized estradiol- and progesterone-treated rats. In estradiol-treated rats, GAD mRNA levels increased in GABAergic neurons associated with the CA1 pyramidal cell layer, but not in the stratum oriens of CA1 or any other region of the hippocampus. Estradiol plus progesterone treatment reversed the estradiol induced increase in GAD mRNA in CA1 and induced a small decrease in the hilus. No effect of estradiol or progesterone was observed in the dorsomedial, ventromedial, or arcuate nuclei of the hypothalamus. Estradiol or progesterone may alter cognitive performance and seizure activity by increasing or decreasing, respectively, the activity of GABAergic neurons in the hippocampus. PMID- 1446612 TI - Divergent roles of protein kinase C in luteinizing hormone biosynthesis versus release in rat anterior pituitary cells. AB - We previously demonstrated that protein kinase C (PKC) activators, i.e. L-alpha 1,2-dioctanoyl glycerol (C8) and phorbol 12-myristate 13-acetate (PMA), mimic the stimulatory effects of GnRH on both LH glycosylation and release. To further evaluate the roles of PKC, we determined: 1) the interaction between PKC activator and GnRH; and 2) the effects of depleting cellular PKC with a high dose of PMA on LH glycosylation vs. release. Anterior pituitaries excised from ovariectomized rats were enzymatically dispersed and cultured. In series 1 experiments, day 3 monolayer cells were incubated in the presence of radiolabeled precursors and GnRH (0, 1, or 100 nM), with or without C8 (200 microM). In series 2 experiments, day 2 cells were pretreated with either PMA (1 microM) or vehicle (0.08% dimethyl sulfoxide) for 24 h and then incubated with diluent, GnRH (1 nM), or PMA (20 nM), and radiolabeled precursors for 4 h. LH translation and glycosylation were monitored by measuring incorporation of [14C]alanine ([14C]A) and [3H]glucosamine ([3H]GA), respectively, into LH. Immunoreactive LH (IRLH) was measured by RIA. In series 1 experiments, C8 increased basal release of IRLH, potentiated IRLH release stimulated by 1 nM GnRH, but not by 100 nM GnRH. C8 elevated total [3H]GA-LH but had no additive effects with GnRH. In series 2 experiments, PMA pretreatment inhibited subsequent PMA-stimulated IRLH release. However, PMA pretreatment did not affect GnRH-induced IRLH release even though PMA pretreatment decreased cellular IRLH content. In comparison, PMA pretreatment reduced both GnRH- and PMA-stimulated total [3H]GA-LH. PMA pretreatment had no effects on total [14C]A-LH in the presence of GnRH or PMA, but reduced the basal level. In summary, PKC activators had no additive effects on either IRLH release or LH glycosylation stimulated by a maximal dose of GnRH. However, PMA pretreatment decreased GnRH-induced LH glycosylation without depressing LH release. These results suggest differential roles of PKC in the actions of GnRH on LH glycosylation vs. LH release. PMID- 1446613 TI - In vivo growth hormone treatment stimulates secretion of very low density lipoprotein by the isolated perfused rat liver. AB - We have previously demonstrated in hepatocyte suspensions prepared after in vivo GH deprivation [hypophysectomy (hypox)] that rates of esterification of [1 14C]oleic acid into triglyceride (TG) and phospholipid (PL) were diminished, and that these esterification rates were correspondingly restored by repletion with recombinant GH. The current studies were designed to determine if GH exerts a similar effect on the secretion of very low density lipoprotein (VLDL), the primary plasma carrier of TG. We assessed rates of secretion of VLDL lipid and apoprotein by perfused livers prepared from cortisol/T3-replaced hypox female rats in the presence and absence of recombinant human (h) GH infusion. We also determined rates of synthesis and secretion of VLDL TG from infused [1-14C]oleic acid. After hypox, rates of secretion of VLDL lipid (TG, PL, and cholesterol) and apoprotein (total) were significantly decreased. In addition, VLDL secreted under these conditions was depleted of PL, relative to the other lipid components. Secretion of newly synthesized VLDL TG from [1-14C]oleic acid was also decreased; however, neither intracellular accumulation of labeled TG nor absolute tissue levels of TG were significantly changed. Conversely, GH treatment of hypox rats effectively restored rates of secretion of VLDL TG, PL, cholesterol (C) and apoprotein to control levels. These findings support the putative role of GH in regulating VLDL secretion in vivo by demonstrating that alterations in plasma GH are accompanied by changes in VLDL secretion. The findings further suggest that GH may regulate VLDL secretion by altering the amount of PL and/or apoprotein available for formation of the VLDL particle. PMID- 1446614 TI - Oxytocin/neurophysin-I messenger ribonucleic acid in bovine granulosa cells increases after the luteinizing hormone (LH) surge and is stimulated by LH in vitro. AB - Bovine granulosa cells express the oxytocin/neurophysin-I (OT/NP-I) gene and secrete OT in vitro. We have shown previously that bovine granulosa cells isolated from the preovulatory follicle after the LH surge secrete 20 times more OT over 5 days in culture than granulosa cells obtained before the surge. LH or FSH stimulates OT secretion in vitro by granulosa cells isolated before the LH surge. We also observed that granulosa cells of preovulatory follicles isolated before the LH surge respond to OT with an increase in progesterone secretion, suggesting that OT may be involved in regulating the follicular/luteal phase shift, or ovulation, in an autocrine fashion. The objective of this study was to determine whether the increase in OT secretion from granulosa cells after the LH surge is regulated at the level of mRNA accumulation, peptide synthesis, and/or peptide secretion. Bovine preovulatory follicles were obtained during the early follicular phase (approximately 36 h before the LH surge), during the midfollicular phase (approximately 12 h before the LH surge), or during the late follicular phase (after the LH surge). Total RNA isolated from granulosa cells and theca interna at the time of cell isolation or after culture with or without LH was subjected to Northern analysis for OT/NP-I mRNA and quantified by densitometry. OT/NP-I mRNA was not detectable or was barely detectable in granulosa cells collected during the early or midfollicular phase (n = 6 and n = 4 follicles, respectively), but a strong hybridization signal was obtained from RNA isolated after the LH surge (n = 5 follicles; P < 0.01). In contrast, OT/NP-I mRNA was not detectable in theca interna before or after the LH surge. Although OT/NP-I mRNA was not detectable in granulosa cells isolated 24 h after prostaglandin F2 alpha injection, after 24 h in culture, a weak OT/NP-I mRNA hybridization signal was observed in RNA from granulosa cells in LH-containing cultures. After 72 h in culture, granulosa cells cultured in control, as well as in LH-containing medium, exhibited a strong signal for OT/NP-I mRNA, but granulosa cells treated with LH exhibited a stronger OT/NP-I hybridization signal than control cultures (P < 0.01). Theca interna did not yield any OT/NP-I hybridization signal initially, and none was induced in culture.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446615 TI - Effect of hypophysectomy on rat preadipocyte replication and differentiation. AB - The effects of hypophysectomy, which results in decreased fat pad weight, fat cell number, and new fat cell formation, on preadipocyte replication were examined. Perirenal and epididymal preadipocytes were cultured from hypophysectomized, sham-operated and unoperated 3-month-old rats. In cloned preadipocytes, hypophysectomy resulted in a 19% decrease in cloning efficiency and a 60% reduction in cell number after 3 weeks in culture. Perirenal cells underwent more extensive replication than epididymal cells. The mechanism of reduced replication following hypophysectomy differed from that of donor site: hypophysectomy resulted in an increased percentage of cells which underwent 2 or fewer population doublings at the expense of cells capable of more than 2 doublings. However, donor site had little effect specifically on these slowly replicating preadipocytes; rather, perirenal preadipocytes underwent more extensive replication than epididymal cells because of the higher percentage of preadipocytes capable of 13 or more doublings in perirenal fat pads. Hypophysectomy did not result in decreased differentiation of preadipocytes. These observations are in accord with the hypothesis that hypophysectomy reduces fat cell number in maturing rats partly through an effect on preadipocyte replicative capacity. Additionally, it seems that more than one form of preadipocyte exists, the various forms having differing susceptibilities to factors such as pituitary function and anatomic site. PMID- 1446616 TI - Tissue-specific transcription start site usage in the leader exons of the rat insulin-like growth factor-I gene: evidence for differential regulation in the developing kidney. AB - The production of insulin-like growth factor-I (IGF-I) in extrahepatic tissues supports both autocrine and paracrine functions and is regulated differently from that in liver, which supports endocrine function. In rat liver, transcription initiation primarily occurs at four distinct, widely separated sites in exon 1 of the IGF-I gene, whereas in exon 2, transcription initiation occurs at a cluster of sites. To understand the molecular basis for tissue-specific regulation of IGF I gene expression, we have mapped transcription start site usage in the following extrahepatic tissues: testes, lung, kidney, heart, brain, muscle, and stomach, with liver serving as a control. In adult rats, kidney and brain exhibited a pattern of exon 1 transcription similar to that seen in liver, i.e. roughly equivalent use of start sites 2 and 3. In contrast, testes and lung preferentially used start site 3, while stomach, heart, and muscle predominantly used start site 3. Start sites 1 and 4 were used in all tissues at extremely low levels. In those tissues studied in which exon 2 transcripts are expressed (testes, lung, stomach, and kidney), the pattern of exon 2 transcription initiation was identical to that in adult rat liver. During postnatal development, the use of all transcription start sites in exons 1 and 2 was coordinate in lung and stomach. Selection of transcription start sites in the kidney, on the other hand, was subject to regulation during postnatal development. Specifically, within exon 1, start site 3 was expressed constitutively throughout peri- and postnatal development. In contrast, the usage of start site 2 was not detected at late fetal or early postnatal stages, but appeared and rapidly increased only at the stage of weaning. Exon 2 transcripts in kidney also did not appear until the postnatal period. These data suggest tissue-specific and developmentally regulated transcription factors regulating IGF-I promoter activity or, alternatively, tissue-specific and developmental stage-dependent differences in the stability of IGF-I mRNAs resulting from the use of different transcription start sites. These different mRNAs may be of significance in the differential regulation of IGF-I production for autocrine or paracrine function. PMID- 1446617 TI - Effects of coadministered growth hormone (GH)-releasing hormone and GH-releasing hexapeptide on maladaptive aspects of obesity in Zucker rats. AB - The purpose of this study was to determine the effect of chronic pharmacological stimulation of the pituitary gland on GH hyposecretion and other maladaptive aspects of obesity. Obese Zucker rats were coadministered GH-releasing hormone (GHRH; 3 micrograms/kg) and GH-releasing hexapeptide (GHRP-6; 300 micrograms/kg), a potent combination of synergistic GH secretagogues, once daily for 60 consecutive days. Although pituitary weights and GH concentrations were higher in obese rats administered the peptides than in obese rats administered saline, stimulated GH secretion was lower in obese rats than in lean rats. However, compared to those in lean rats, plasma insulin-like growth factor-I and insulin concentrations were higher in the obese rats regardless of treatment. The GH secretagogues did not alter food intake or body weight gain in sexually mature obese rats, whereas body weight gain was significantly increased when they were administered to prepubertal obese rats. Although glucose tolerance was impaired in both groups of obese rats, it improved in obese rats administered GHRH and GHRP-6 compared to that in obese rats administered saline. On the other hand, plasma cholesterol concentrations were elevated in obese rats administered the GH secretagogues but not saline. In conclusion, the results of this study suggest that hyposensitivity to GHRH and GHRP-6 in obese Zucker rats results from high concentrations of plasma insulin-like growth factor-I that negatively feedback on stimulated GH secretion. Nonetheless, daily episodes of endogenous GH secretion resulting from chronic coadministration of GH secretagogues significantly influenced the pituitary gland as well as lipid and carbohydrate metabolism. PMID- 1446618 TI - Thyroxine binding to the apolipoproteins of high density lipoproteins HDL2 and HDL3. AB - Four preparations of high density lipoprotein HDL2, five of HDL3, and purified apolipoproteins apoA-I, apoA-IV, and apoE were photoaffinity labeled with [125I]T4 and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gels were also immunoblotted with antiserum against apoA-I, apoA II, apoA-IV, apoE, or apo(a), and the immunostained membrane was then autoradiographed. In HDL2, the two major radioactive bands migrated near the origin of the resolving gel and at 28-31 kilodaltons (kDa). The first band, stained by anti-apo(a) and anti-apoB-100, accounted for 40-96% of the total radioactivity and was attributed to lipoprotein(a), which is isolated in the same density range as HDL2. The second band, stained by anti-apoA-I, accounted for 1 57% [41-95% after correction for contaminating lipoprotein(a)] of the [125I]T4 in the resolving gel. In HDL3, the major radioactive band was identified as apoA-I and contained 93-94% of the [125I]T4 in the resolving gel. Minor radioactive bands in both HDL2 and HDL3 were identified as apoA-II (17-18 kDa), apoA-II monomer (7-10 kDa), apoE (36-38 kDa), and apoAII-apoE heterodimer (46 kDa). In addition, HDL3 contained apoA-IV (43 kDa). Photoaffinity labeling of isolated apoA-IV and apoE showed that each protein interacted with [125I]T4. In both HDL2 and HDL3, photoaffinity labeling in the presence of unlabeled L-T4 (1-10 microM) showed inhibition, suggesting a Kd in the micromolar range. This inhibition varied among different apo bands of the same HDL2 or HDL3 preparation and among the same bands of different preparations. Labeling in the presence of heparin or other inhibitors of T4 binding to plasma proteins (furosemide, diclofenac, and mefenamic acid) showed that HDL2-associated apoA-I was more sensitive to inhibition than HDL3-associated apoA-I. In conclusion, 1) HDL2 and HDL3 carry T4 mainly through apoA-I and secondarily through apoA-II and apoE. The inter- and intrasubclass variations in T4 binding and sensitivity to inhibitors can be explained by the known heterogeneity of HDL particles and possible differences in conformation of the apo. The findings reported here, that apo other than apoA-I and apoB exhibit saturable binding of T4, suggest that thyroid hormone lipoprotein interactions may have even wider physiological implications than previously appreciated. PMID- 1446619 TI - A surge of gonadotropin-releasing hormone accompanies the estradiol-induced gonadotropin surge in the rhesus monkey. AB - In several species, the ovulatory LH surge is preceded by a surge of GnRH. Although a role for estradiol in the initiation of the LH surge is well established in the primate, several observations in the rhesus monkey have questioned whether such an estradiol-induced neurosecretory event takes place. We report on GnRH measurements in cerebrospinal fluid (CSF) samples obtained from the third ventricle of intact and ovariectomized (OVX) conscious rhesus monkeys during control periods and throughout the estradiol-induced positive feedback phase. In the first experiment, we measured control GnRH concentrations in CSF collected at 15-min intervals uninterruptedly for a period of 1-5 days in tethered OVX monkeys (n = 4) in their cages without steroid priming. As had been demonstrated previously with the same method in restrained animals, CSF from the third ventricle contained detectable amounts of GnRH. Spontaneous GnRH secretion was pulsatile; overall mean pulse interval was 67.4 (+/- 2.2 SE) min for a total of 177 GnRH pulses. During 2 periods (8 and 6 h) when simultaneous blood and CSF samples were obtained, 14 out of 15 GnRH pulses were accompanied by an LH pulse. To evaluate the effects of an estrogen challenge on GnRH secretion, estradiol benzoate (E2B; 330 micrograms) was given to 4 intact (5 experiments) and to 2 OVX monkeys. CSF collection was initiated 8-24 h before E2B injection and continued for 72-84 h thereafter. E2B administration resulted in a surge of LH and of GnRH in all but one experiment. The mean time of onset of the GnRH surge was 22.0 (+/- 4.0) h after E2B, whereas that of the LH surge was 24.7 (+/- 3.4) h. In contrast to LH, which declined after a peak at 35.2 +/- 3.9 h, the increase in GnRH secretion persisted throughout most of the observation period. The magnitude of the GnRH response differed in the 2 groups; in the intact animals, mean peak GnRH concentration increased 8.9-fold but only 3.8-fold in the OVX monkeys. A similar GnRH surge was observed in 1 OVX monkey, receiving an iv infusion of E2, which produced more physiological concentrations of E2. In this animal, an initial suppression of GnRH concentration in the 24-48 h period after E2 (GnRH control, 14.6 +/- 1.9; post-E2, 4.0 +/- 0.5 pg/ml) preceded the initiation of the GnRH surge which occurred at 54 h after E2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446620 TI - Differential actions of endothelin and gonadotropin-releasing hormone in pituitary gonadotrophs. AB - Endothelin (ET) and GnRH act through specific receptors to promote Ca2+ mobilization and influx pathways in pituitary gonadotrophs. In the present study cytoplasmic calcium ([Ca2+]i) and secretory responses to these two agonists are compared. In single gonadotrophs, low concentrations of both agonists cause oscillatory [Ca2+]i responses after a latent period. Such responses usually consist of discrete transients arising from the normal resting level, but are sometimes super-imposed on an elevated basal calcium level. At high doses, ET-1 and GnRH induce biphasic responses, composed of a spike phase followed by a plateau that often shows high frequency and low amplitude Ca2+ transients. The duration of the latent period and the frequency of the subsequent oscillations are correlated, and both are dependent on agonist concentration. The frequencies and amplitudes of Ca2+ spiking are also interrelated; increases in frequency are followed by more rapid decreases in the amplitude of the Ca2+ transients. After K(+)-induced depolarization, gonadotrophs retain their oscillatory Ca2+ responses to ET-1 and GnRH, with the same frequency as controls. Activation of protein kinase-C by phorbol esters does not alter the frequency of ET-induced Ca2+ transients, but significantly reduces their amplitudes. In contrast, treatment with nanomolar concentrations of thapsigargin converts ET-induced oscillations into a biphasic response, suggesting that Ca(2+)-ATPase in the endoplasmic reticulum participates in the oscillatory mechanism. The two agonists differ in their threshold doses and concentration dependence, ET being significantly less potent than GnRH. Also, gonadotrophs stimulated by ET-1 exhibit different post treatment responsiveness than those exposed to GnRH. While GnRH-treated cells recover their full [Ca2+]i and secretory responses within 30 min as well as normal [Ca2+]i and secretory responses to ET-1, endothelin-treated cells are refractory to further stimulation with ET and exhibit either attenuated or enhanced Ca2+ and LH responses to GnRH, depending on the duration of exposure to ET-1 and the subsequent recovery period. These data indicate that both receptors use the same mechanism(s) for Ca2+ release, but have different capacities to generate, maintain, and reinitiate the Ca2+ signal. PMID- 1446621 TI - Quantification and cellular localization of ovine placental lactogen messenger ribonucleic acid expression during mid- and late gestation. AB - Ovine placental lactogen (oPL) is structurally similar to PRL, is a product of the chorionic epithelium, and has been implicated in playing a supportive role in fetal growth. This study examined the concentration and cellular location of oPL mRNA at five stages of pregnancy (days 60, 90, 105, 120, and 135) in 21 cross bred ewes, and results were compared to maternal and fetal serum oPL concentrations, cotyledonary DNA and actin mRNA concentrations, and total fetal weight. The concentration of oPL mRNA in fetal cotyledonary tissue increased (P < or = 0.05) from day 60 (15.4 pg/micrograms total cellular RNA) to day 120 (73.7 pg/micrograms total cellular RNA) of gestation and then plateaued, whereas no significant changes occurred in the concentration of actin mRNA over the gestational ages examined. The concentration of DNA in cotyledonary tissue (micrograms per mg wet tissue) increased (P < or = 0.05) from days 60 through 120 and remained constant through day 135, such that when oPL mRNA was expressed on a picogram per microgram DNA basis, no stage of gestation effect (P > or = 0.10) was observed. The maternal serum oPL concentration increased (P < or = 0.05) from day 60 (7.1 ng/ml) to day 105 (417.7 ng/ml), followed by a large but nonsignificant (P > or = 0.10) increase in maternal serum oPL occurring on day 135 (902.0 ng/ml). Fetal serum oPL concentrations increased (P < or = 0.05) from day 60 (11.0 ng/ml) to day 90 (29.0 ng/ml) and then remained relatively constant. Maternal serum oPL (r = 0.68; P < or = 0.01) and cotyledonary oPL mRNA levels (r = 0.61; P < or = 0.05) were correlated with total fetal weight when adjusted for fetal number and gestational age, and together accounted for 80.6% (r2 value) of the variation found in total fetal weight. The correlation between fetal serum oPL concentrations and total fetal weight was nonsignificant (P < or = 0.10). Examination of placentome cross-sections by immunocytochemistry and in situ hybridization at the five gestational ages indicated that the chorionic binucleate cell was the sole source of oPL. These data provide evidence that, like maternal serum concentrations of oPL, oPL mRNA expression by chorionic binucleate cells increases until late gestation, whereas fetal serum concentrations of oPL plateau during midgestation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446622 TI - Leydig cell peroxisomes and sterol carrier protein-2 in luteinizing hormone deprived rats. AB - We investigated the effects of 8 days of LH withdrawal on rat Leydig cell peroxisomal volume, total and intraperoxisomal catalase and sterol carrier protein-2 (SCP2) contents, and LH-stimulated testosterone secretion in vitro. Three groups of adult male Sprague-Dawley rats, i.e. control, TE-implanted (testosterone-17 beta-estradiol-filled Silastic implants to suppress LH), and TELH-implanted (TE-implanted and LH replacement via Alzet mini osmotic pumps), were used. After 8 days, Leydig cell organelle volumes (stereology), intraperoxisomal catalase and SCP2 contents (immunocytochemistry), LH-stimulated testosterone secretion by isolated Leydig cells in vitro (determined by RIA), and total catalase and SCP2 contents in equal numbers of Leydig cells (immunoblot analyses) were determined. Results showed that the TELH-implanted rats were identical to controls in every parameter tested. Testis volume and Leydig cell number per testis in control and TE-implanted rats were not significantly different; however, reductions (P < 0.05) were observed in the average volume of a Leydig cell (one third of controls) and the volume of Leydig cells per testis. All Leydig cell organelle volumes tested were significantly lower in TE-implanted rats than in the controls; however, the volumes of smooth endoplasmic reticulum (SER) and peroxisomes were the most reduced (lowered to one sixth of control values). LH-stimulated testosterone secretion per Leydig cell in vitro correlated well with these changes in the volumes of Leydig cell SER and peroxisomes. Intraperoxisomal catalase in Leydig cells was unchanged in TE-implanted rats, although immunoblotting demonstrated a loss of total catalase content (which reflected the reduction in the volume of peroxisomes). SCP2 in Leydig cells of TE implanted rats was undetectable with immunoblot analysis (explained by the reductions in Leydig cell peroxisome volume and intraperoxisomal SCP2). These results demonstrate that the organelles SER and peroxisomes and the protein SCP2 in Leydig cells are more LH dependent than the other organelles (e.g. mitochondria, lysosomes) and protein catalase, respectively. Moreover, the findings of this study are consistent with the hypothesis that Leydig cell peroxisomes play a significant role in testosterone production. PMID- 1446623 TI - Identification, partial purification, and characterization of two guanosine triphosphate-binding proteins associated with insulin receptors. AB - We have previously suggested that at least two different G-proteins are involved in mediating insulin receptor functions. Here we identify and partially purify two G-proteins with apparent molecular masses of 41 and 67 kilodaltons (kDa) that interact with insulin receptors in rat adipocytes and human placenta. Treatment of isolated rat adipocytes with insulin inhibited pertussis toxin-catalyzed ADP ribosylation of a 41-kDa G-protein in subsequently isolated plasma membranes by 30.2 +/- 3.0% and in partially purified insulin receptor preparations by 35.6 +/- 5.7%. There was no associated decrease in the concentration of the 41-kDa G protein in the plasma membranes, as determined by immunoblot with a common G alpha antibody. The common G alpha antibody also recognized a 67-kDa protein in the plasma membranes, the concentration of which was not affected by insulin. However, the 67-kDa protein was enriched in partially purified solubilized insulin receptor preparations. Two similar, 41- and 67-kDa G-proteins were identified in the wheat germ-purified insulin receptor preparations obtained from human placenta. Removal of these two G-proteins from insulin receptor preparations results in loss of the ability of insulin to stimulate receptor kinase activity. Addition of a fraction enriched with 41- and 67-kDa G-proteins to the G-protein-depleted insulin receptor restores the insulin sensitivity of the insulin receptor kinase activity. Furthermore, addition of G-protein-depleted insulin receptors to the fraction containing partially purified 41- and 67-kDa G proteins enhances pertussis toxin-catalyzed ADP-ribosylation of the 41-kDa G protein. These results indicate that either the 41- or 67-kDa G-protein, or both, interact with the insulin receptor mediating insulin receptor kinase activity. Such mutual interaction and regulation between the insulin receptor and G proteins could be an important component of the signal transduction mechanism for insulin. PMID- 1446624 TI - Multiple regulatory effects by transforming growth factor-beta on type I collagen levels in osteoblast-enriched cultures from fetal rat bone. AB - Transforming growth factor-beta (TGF beta) stimulates bone formation in vivo and in vitro, related in part to an increase in type I collagen production. In osteoblast-enriched cultures from fetal rat bone, 24- to 48-h TGF beta 1 treatment enhanced collagen synthesis rates by 2.5- to 6-fold, while it increased collagen accumulation by 5- to 10-fold. These effects were not accounted for by similar changes in acid-soluble radioisotope, cell number, or steady state type I procollagen transcripts. Basal collagen synthesis and accumulation were markedly reduced when mRNA transcription was blocked with alpha-amanitin, but the relative stimulatory effects of TGF beta 1 persisted in toxin-treated cultures. Newly synthesized collagen was rapidly secreted into the culture medium. While pulse chase studies demonstrated that total (medium plus cell-associated) collagen levels were stable throughout the 48-h period, TGF beta 1 increased the fraction of cell-associated collagen between 24-48 h, and this was partially blocked by alpha-amanitin, but not by antibody to fibronectin or beta 1-integrin subunit. TGF beta 1, therefore, has multiple effects on type I collagen in fetal bone derived cell cultures, including small increases in mRNA, large increases in polypeptide synthesis, and enhanced association of secreted collagen to the cell layer, which may require synthesis of extracellular components unrelated to fibronectin or the beta 1-integrin subunit. PMID- 1446625 TI - Testicular descent. III. The neonatal mouse gubernaculum shows rhythmic contraction in organ culture in response to calcitonin gene-related peptide. AB - The effects of calcitonin gene-related peptide (CGRP) and CGRP 8-37 on the neonatal mouse gubernaculum were examined in organ culture, with the aim of seeing whether CGRP has a direct effect on the gubernaculum. A total of 440 gubernacula were studied. Two hundred and fifty gubernacula were treated with CGRP in concentrations ranging from 0-714 nM/liter. With increasing doses of CGRP the percentage of gubernacula showing vigorous contraction increased from 18-50%. The total percentage of gubernacula showing any form of contraction increased from 76-96%. One hundred and fifty gubernacula were exposed to the CGRP analog CGRP 8-37. Increasing concentrations of CGRP 8-37 from 179-714 nM/liter decreased the rate of vigorous contraction from 18-4%. The percentage of gubernacula showing any degree of contraction decreased from 76-14%. Forty gubernacula removed from testicular feminization (TFM) mice were exposed to varying concentrations of CGRP. In the absence of exogenous CGRP no contractility was observed. By contrast, in the presence of CGRP the gubernacula showed vigorous contractility increasing from 38-90%. The total number of gubernacula showing contraction increased from 75-100%. These studies demonstrated that the neonatal mouse gubernaculum exhibits a high level of endogenous contractility, which can be enhanced in a dose responsive manner with exogenous CGRP. CGRP 8-37 caused a dose responsive inhibition. The androgen-insensitive gubernaculum from the TFM mouse showed no endogenous contraction, but on exposure to CGRP showed an enhanced rate of contractility. These results are consistent with the hypothesis that androgens may control gubernacular migration indirectly via release of CGRP from the genitofemoral nerve in the inguinoscrotal region. The failure of gubernacular motility in vitro and migration in vivo in the TFM mouse may indicate lack of CGRP release from the genitofemoral nerve. PMID- 1446626 TI - Photoperiodic induction in vitro: the dynamics of gonadotropin-releasing hormone release from hypothalamic explants of the Japanese quail. AB - The Japanese quail is a photoperiodic animal that under certain experimental conditions can respond to a single long day with a wave of LH secretion. Such a system offers an opportunity to analyze the photoneuroendocrine changes as they occur in real time, especially as all of the neural machinery (photoreceptor, clock, and GnRH system) is believed to lie within the hypothalamus. The first detectable rise in LH occurs at about hour 23 of the long day, and this single inductive event leads to prolonged LH secretion lasting for up to 2 weeks and peaking 2-4 days after the dawn of the long day. The size of the quail's hypothalamus is such that the entire structure, including both the GnRH cell bodies and the median eminence, can be cultured for some hours, and the rates of GnRH release measured therefrom. The present experiments used hypothalamic explants from quail at different times throughout the photoperiodic response, superfused them for up to 7.5 h in vitro, and measured the dynamics of GnRH release. A significant step increase of 80% in GnRH release occurred between hours 22.5 and 23 in quail that had been exposed to a long day: an equivalent change was not found in hypothalami taken from quail maintained only under short day lengths. In explants taken from quail at the peak of LH secretion (53 h after dawn of the long day), the rates of GnRH release were double those found in control quail not exposed to the long day. Explants taken 14 days after the long day, when LH secretion had subsided fully, showed no difference in GnRH release between photo-stimulated and control quail. These results suggest that photoperiodic induction involves a timed increase in GnRH release, and the rise at hour 23 is believed to represent photoperiodic induction actually taking place within the brain in vitro. They also suggest that the wave of LH secretion triggered by the single long day is, at least in part, a neuroendocrine or neural phenomenon; this confirms earlier indirect evidence to this effect. PMID- 1446627 TI - Effects of adrenal androgens on the transplantable human prostate tumor PC-82. AB - The potential of the adrenal androgens androstenedione (A) and dehydroepiandrosterone (DHEA) to stimulate prostate tumor growth was investigated in the hormone-dependent human prostate tumor model PC-82, propagated in nude mice. Substitution of castrated mice bearing growth-arrested tumors with DHEA for 28 days, resulting in peripheral levels of 9.2 +/- 1.7 nmol/liter (mean +/- SEM), led to a decline of tumor burden comparable to that observed in castrated controls. Intratumor testosterone (T) and 5 alpha-dihydrotestosterone were similar to those detected in the castrated group. In contrast, high-dose A supplementation (peripheral level of 13.5 +/- 1.3 nmol/liter) in androgen ablated tumor-bearing mice resulted in tumor growth, although less pronounced than in T resubstituted mice (T level of 18.8 +/- 1.5 nmol/l). Intraprostatic levels of androgens were not different between both groups. Substitution of castrated PC-82 tumor-bearing mice with low-dose A (2.5 +/- 0.4 nmol/l) neither stimulated growth of tumors nor did it lead to regression of PC-82 tumors. Proliferative activity as estimated by BrdU incorporation (S-phase cells) was not induced in these tumors. In conclusion, DHEA does not have a stimulatory effect on growth of PC-82 tumor tissue, but A is capable of inducing PC-82 tumor growth, most likely through peripheral conversion of A into T and 5 alpha-dihydrotestosterone. PMID- 1446628 TI - Regulation of the hepatic growth hormone receptor and serum growth hormone binding protein during pregnancy in the mouse: effects of litter size. AB - The regulation of hepatic GH receptor (GHR) and serum GH-binding protein (GHBP) during pregnancy in the mouse was investigated by manipulating the number of conceptuses carried by the dam. Animals carrying 1-4 conceptuses had significantly lower amounts of hepatic GHR (GH-binding activity) than mice carrying 10-13 conceptuses on days 9 and 13 of pregnancy. There was no significant difference in hepatic GHR on day 17 of pregnancy between animals carrying 1-4 and 10-13 conceptuses. Animals carrying 1-4 conceptuses had significantly lower concentrations of GHBP in serum than animals carrying 10-13 conceptuses on days 9, 13, and 17 of pregnancy. The relative amounts of liver GHR and GHBP-encoding messages in animals with low and high conceptus numbers were investigated by Northern analysis. There were higher levels of both messages in animals carrying 10-13 conceptuses than in mice carrying 1-4 conceptuses. On day 13 of pregnancy, animals carrying 10-13 conceptuses had significantly higher levels of GHBP-encoding message than animals carrying 1-4 conceptuses. Total hepatic mass was not significantly different between animals with low and high conceptus numbers. No significant difference was found in GHBP concentration between blood from the uterine vein and the trunk in 17-day pregnant animals. Mouse placental lactogen-I (mPL-I), mPL-II, GH, and corticosterone concentrations were measured by RIA and related to hepatic GHR activity and serum GHBP concentration. Hepatic GHR activity and serum GHBP concentration were significantly correlated with each other on days 9, 13, and 17 of pregnancy. Hepatic GHR activity was significantly correlated with mPL-I and mPL-II on day 9 of pregnancy. GHBP concentration was significantly correlated with mPL-I and mPL II on day 9 of pregnancy and with mPL-II and GH on day 13 of pregnancy. Data are consistent with the hypothesis that mPL-I, mPL-II, and GH may affect hepatic expression of the GHR/GHBP gene during pregnancy in the mouse. PMID- 1446629 TI - Thyroid hormone synthesis in thyroglobulin secreted by porcine thyroid cells cultured on porous bottom chambers. Effect of iodide. AB - The long-term iodination of thyroglobulin secreted into the apical medium of thyroid cells cultured as monolayers on porous bottom chambers reached 5.87 +/- 1.66 atoms of iodine/mol thyroglobulin after 11 days incubation in the presence of TSH (0.1 mU/ml) and iodide (0.5 microM) in the basal medium. This iodinated thyroglobulin contained thyroid hormones (T3 + T4) which involved 22.7% of the thyroglobulin iodine content. The iodoamino acid content was, in residues per mole, 2.2 +/- 0.35 for monoiodotyrosine, 0.74 +/- 0.04 for diiodotyrosine, 0.23 +/- 0.04 for T4, and 0.098 +/- 0.02 for T3. Kinetic studies showed that a minimal level of iodination (2.05 +/- 0.26 atoms iodine/mol thyroglobulin) was necessary for hormonogenesis. A maximal level of iodination and hormonogenesis was obtained with 0.5 microM iodide added daily to the basal medium. In these conditions, hormonogenesis efficiency reached about 40% (a value close to this one observed in vivo). Above 0.5 microM iodide, both iodination and T4 synthesis were inhibited (28.3% and 73.9%, respectively, for 1 microM iodide). Our culture system makes it possible to demonstrate that this high iodide concentration in the basal medium did not increase apical iodide concentration above 10 microM but decreased apical thyroglobulin concentration. The inhibitory effect of iodide on hormonogenesis cannot be due to a competition with tyrosine residues of thyroglobulin for their binding to thyroperoxidase although it could be related, at least in part, to a decrease in protein synthesis. PMID- 1446630 TI - Basic fibroblast growth factor (bFGF) gene expression and protein production during pubertal development of the seminiferous tubule: follicle-stimulating hormone-induced Sertoli cell bFGF expression. AB - The potential role of basic fibroblast growth factor (bFGF) as a mediator of cell cell interactions in the growth and development of the testis was examined. Nuclease protection analysis was used to evaluate bFGF gene expression in the testis and other male reproductive tract tissues. bFGF expression was evident in seminal vesicle, prostate, epididymis, and, at low levels, testis of 20-day-old rats. The developmental expression of bFGF in whole testis and isolated somatic cells types was determined. Mesenchymal-derived peritubular cells and epithelial like Sertoli cells were isolated from prepubertal, midpubertal, and late pubertal rat testes. In whole testis, bFGF expression is predominant early in prepubertal testicular development and decreases with sexual maturity. Both freshly isolated peritubular and Sertoli cells express bFGF at relatively constant levels during pubertal development, with a slight suppression at the late pubertal stages. Freshly isolated mature Leydig cells also expressed low levels of bFGF. Cultured Sertoli and peritubular cells produced bFGF-like proteins, including 18- and 24 kilodalton forms. Interestingly, FSH increased Sertoli cell bFGF gene expression and protein production. Previously, FSH and bFGF have been shown to stimulate immature Sertoli cell growth. The results of the current study suggest that the ability of FSH to regulate testis and Sertoli cell proliferation may in part be indirectly mediated through the local production and action of bFGF. bFGF has also previously been shown to localize in developing germinal cells. Therefore, FSH-induced Sertoli cell bFGF expression may mediate Sertoli-germinal cell interactions involved in the control of the spermatogenic process. Observations demonstrate the presence of bFGF at a time coinciding with active growth of the somatic cell populations of the seminiferous tubule. Potential roles for bFGF in the seminiferous tubule to consider include angiogenesis of the tubule, prepubertal Sertoli cell proliferation, and mediating Sertoli-germinal cell interactions. PMID- 1446631 TI - Effects of long-term infusions of dopa and carbidopa on renin and steroid secretion in the rat. AB - Plasma, kidney, and adrenal catecholamine concentrations were varied by infusing rats with L-dopa and/or carbidopa for 2 weeks. L-Dopa infusion (300 micrograms/day) increased dopamine concentrations in plasma, adrenal zona glomerulosa, and kidney by 140%, 74%, and 224%, respectively: the dopamine content of the adrenal inner cortex plus medulla was not increased. Infusion of carbidopa alone had no detectable effect upon endogenous dopamine concentrations. Concomitant infusion (300 micrograms/day) of carbidopa with L-dopa blocked the rise in plasma and adrenocortical dopamine caused by L-dopa alone. Plasma aldosterone and plasma and kidney active renin concentrations were unaffected by L-dopa administration but plasma corticosterone and deoxycorticosterone (DOC) were significantly elevated (P < 0.05); increases in DOC appeared greater than those of corticosterone. These data cast doubt on the theory that dopamine is a physiological tonic inhibitor of aldosterone synthesis in rats. However, in the rat, stimulatory effects of L-dopa on plasma concentrations of precursors of aldosterone might be of physiological significance since DOC is a potent mineralocorticoid. PMID- 1446632 TI - Neuropeptide Y potentiates luteinizing hormone (LH)-releasing hormone-induced LH secretion only under conditions leading to preovulatory LH surges. AB - We recently demonstrated that neuropeptide Y (NPY) potentiates the ability of pulsatile LHRH infusions to restore LH surges in pentobarbital (PB)-blocked, proestrous rats. In the present study we determined if specific endocrine conditions are necessary for the expression of these direct pituitary effects of NPY. Facilitatory actions of NPY were examined in the absence of gonadal feedback [ovariectomy (OVX)], in the presence of negative gonadal feedback (metestrus), after estrogen priming of the pituitary gland [OVX plus 30 micrograms estradiol benzoate (EB) 2 days before experiments], and after treatments which evoke preovulatory-like LH surges (OVX plus EB and 5 mg progesterone or P the morning of experiments). Rats received jugular catheter implants the day before experiments. On the day of experiments, hourly blood samples were taken from 1100 2100 h. At 1330 h, rats received injections of PB to block endogenous LHRH release, or saline. Every 30 min from 1400-1800 h, PB-treated rats received iv pulses of LHRH (15 ng/pulse) or saline, along with concurrent pulses of NPY (1 or 5 micrograms/pulse) or saline. Plasma samples were analyzed by LH RIA. In all cases, pulsatile administration of 15 ng LHRH resulted in plasma LH levels that were significantly elevated above saline-treated, PB-blocked controls. Only in the case of EB+P-treated rats did coadministration of 5 micrograms NPY along with LHRH significantly enhance LHRH-stimulated LH secretion (P < 0.001). NPY had no effect on LHRH-stimulated LH secretion in OVX, OVX + EB-treated, or metestrous rats. Pulsatile administration of either dose of NPY alone did not stimulate LH release in any of the four groups examined. These results demonstrate that the facilitatory effects of NPY on LHRH-stimulated LH secretion can be manifest only under the endocrine conditions required to produce full, preovulatory-like LH surges, i.e. after estrogen and P treatment. PMID- 1446633 TI - Neuropeptide Y gene expression in the arcuate nucleus is increased during preovulatory luteinizing hormone surges. AB - Recent studies have suggested that neuropeptide Y (NPY) plays an important role in the induction of the preovulatory LH surge. The present study was performed in order to determine if a change in NPY gene expression within arcuate nucleus NPY neurons is associated with the generation of the preovulatory LH surge. In Exp 1, in situ hybridization was used to measure NPY messenger RNA (mRNA) levels in the arcuate nucleus of female rats at 0900 h and every 2 h from 1400-2200 h on the day of proestrus (PRO). Comparisons between groups showed a clear, stepwise increase in NPY gene expression throughout the day of PRO. At 1600 h, when LH values were significantly greater than 0900 h values, NPY mRNA labeling intensities in the arcuate nucleus were significantly greater than 0900 h levels (P < 0.01). By 1800 h, the time at which the LH surge peaked, NPY mRNA levels also peaked and were nearly 3-fold greater than levels observed at 0900 h (P < 0.01). NPY mRNA levels at 2000 h and 2200 h remained elevated above 0900 h levels (P < 0.01) but by 2000 h had decreased significantly from 1800 h levels (P < 0.05). In Exp 2, NPY mRNA levels were measured once again at 0900 h and 1800 h on PRO, and then at 0900 h and 1800 h on metestrus (MET), in order to determine if the change in gene expression seen in Exp 1 was unique to the day of PRO, or if it simply reflected a daily rhythm of gene expression in the nucleus. Analysis of mRNA levels showed no difference in NPY mRNA levels between 0900-1800 h on MET. Also, NPY mRNA levels at 0900 h and 1800 h on MET were significantly less than levels at 1800 h on PRO (P < 0.01). These results are consistent with the hypothesis that NPY neurons participate in the generation of LH surges through increased production of NPY and subsequent potentiation of the release and/or actions of LHRH. PMID- 1446634 TI - Aging abolishes the estradiol-induced suppression and diurnal rhythm of proopiomelanocortin gene expression in the arcuate nucleus. AB - The diurnal rhythms of many physiological functions are disrupted during aging. Underlying these disruptions are age-related alterations in the activity of neurotransmitters and/or their receptors. Estradiol has a significant influence on the pattern of the diurnal rhythms in neurotransmitter function, and responsiveness to estradiol changes with age. We assessed POMC mRNA levels in the arcuate nucleus of young, middle-aged, and old female rats to determine whether aging alters the diurnal rhythm of POMC gene expression in ovariectomized rats and/or changes the responsiveness to estradiol. In addition, we measured serum LH, PRL, and corticosterone levels to evaluate any age-associated interactions between these hormones and POMC mRNA levels. In young animals, estradiol treatment induced a diurnal rhythm and suppressed mean levels of POMC mRNA. In the middle-aged and old rats, the ability of estradiol to suppress POMC mRNA levels and to allow the expression of a diurnal rhythm of POMC mRNA was abolished. Although age-associated changes occurred in serum concentrations of LH, PRL, and corticosterone, they did not correlate with the changes in POMC gene expression. Therefore, our data demonstrate that age-related changes in hypothalamic POMC gene expression do not determine the changes in pituitary hormone secretion. Instead, they suggest that fundamental changes in diurnal function or in the biological clock underlie and differentially regulate the age related changes in POMC gene expression and LH, PRL, and corticosterone secretion. PMID- 1446635 TI - Neuropeptide Y release from the paraventricular nucleus increases in association with hyperphagia in streptozotocin-induced diabetic rats. AB - We tested the hypothesis that the hyperphagia observed in streptozotocin (STZ) induced diabetic rats is due to increased release of neuropeptide Y (NPY) in the paraventricular nucleus (PVN) of the hypothalamus. In the first experiment, male rats were injected with STZ or vehicle (control) via the tail vein and 18-20 days later, NPY levels in seven hypothalamic sites and release in vitro from selected hypothalamic sites were evaluated. The results showed that in association with STZ-produced marked hyperglycemia and hyperphagia, NPY concentrations were increased in four hypothalamic sites, including the PVN. Evaluation of NPY release in vitro showed that both basal and KCl-induced release was significantly higher from the micro-dissected PVN of STZ-treated than control rats. A similar augmentation in the NPY efflux in vitro was detected from the median eminence arcuate nucleus, but not from the neighboring ventromedial nucleus of STZ-treated rats. In the second experiment, rats were treated with STZ or vehicle and received permanent push-pull cannula (PPC) in the PVN for evaluation of NPY release in vivo 18-21 days after STZ treatment. The results showed that mean NPY levels in the perfusates collected from the PVN of diabetic rats were significantly higher as compared to control rats. Since NPY is the most potent naturally occurring orexigenic signal and the PVN is an important initial site of NPY action in the stimulatory pathway regulating feeding, our findings of augmented PVN NPY release in vivo and in vitro are in accord with the hypothesis that increased NPY secretion in the PVN may be responsible for hyperphagia in diabetic rats. PMID- 1446636 TI - Regulation of human cytochrome P450scc and adrenodoxin messenger ribonucleic acids in JEG-3 cytotrophoblast cells. AB - Cycloheximide generally inhibits steroidogenesis, but has different effects on the accumulation of the mRNAs for various steroidogenic enzymes in different species, tissues, and cell lines. In bovine adrenocortical cells, cycloheximide prevents ACTH- or cAMP-induced accumulation of the mRNAs for cytochrome P450scc and adrenodoxin, but in human cells, cycloheximide induces the accumulation of adrenodoxin mRNA. To study the potential role of the 3'-untranslated regions, and especially the AU-rich regions, of adrenodoxin and P450scc mRNAs in cycloheximide sensitive regulation of mRNA accumulation, we constructed a series of vectors expressing P450scc or adrenodoxin mRNA with its own or each other's 3' untranslated sequences and transfected them into human JEG-3 cytotrophoblast cells. Removal of the AU-rich 3'-untranslated sequences of adrenodoxin mRNA and replacing them with the 3'-untranslated region of P450scc did not alter the abundance or apparent stability of this mRNA, or its inducibility by cycloheximide or cAMP. Substituting the AU-rich 3'-untranslated region of adrenodoxin mRNA (which contains three copies of the AUUUA sequence) for the 3' untranslated region of P450scc did not alter the inducibility of P450scc mRNA with forskolin. Inhibition of transcription with actinomycin-D elicited no difference in the adrenodoxin mRNA half-life in JEG-3 cells treated with forskolin, cycloheximide, or both. RNA polymerase run-on assays show little effect of forskolin on adrenodoxin gene transcription, while P450scc gene transcription was induced. These data suggest that the principal means for regulating P450scc mRNA is transcriptional, while the principal regulation of adrenodoxin is posttranscriptional. This posttranscriptional regulation of adrenodoxin mRNA is not mediated by the AUUUA sequences or other segments of the 3'-untranslated region. PMID- 1446637 TI - Human thymocytes express a prolactin-like messenger ribonucleic acid and synthesize bioactive prolactin-like proteins. AB - Recent evidence has demonstrated an important immunoregulatory role for pituitary PRL. Moreover, PRLs have been identified as products of transformed human lymphocyte cell lines and normal murine lymphocytes, and implicated as regulators of their proliferative responses. However, PRL synthesis by normal human lymphocytes has not yet been reported. Here we demonstrate that human thymocytes and peripheral blood lymphocytes (PBL) synthesize PRL in primary culture. The principal form produced by thymocytes is 24 kilodaltons (kDa), essentially the same size as pituitary PRL, while PBL produced a 27-kDa variant. Size heterogeneity was evident, with products detected ranging from 21-29 kDa in various tissue samples, a phenomenon also found to occur in human pituitary and decidual PRL. Thymocytes and PBLs also synthesized a low mol wt form (11 kDa) that was released into culture supernatants concurrently with the larger PRL. The 24- and 11-kDa forms expressed PRL-like bioactivity in the Nb2 node lymphoma bioassay, further supporting their PRL-like nature. Expression of these PRLs was regulated by mitogen stimulation in thymocytes, but was constitutively produced in PBL. Northern blot analysis of thymocyte RNA using a human PRL cDNA probe detected a single PRL-like mRNA, which was significantly larger than human pituitary PRL mRNA. This was constitutively present in unstimulated thymocytes. Taken together, these data demonstrate that normal human lymphocytes synthesize bioactive PRLs similar in size to those produced by the pituitary. The presence of a single PRL mRNA suggests that the size variation observed in these proteins is probably due to posttranslational modification, such as proteolysis and glycosylation. PMID- 1446638 TI - Regulation of 3-ketosteroid reductase messenger ribonucleic acid levels and 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase activity in rat liver by sex steroids and pituitary hormones. AB - We have recently characterized three types of complementary DNA clones encoding predicted isoenzymes of the rat 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) family. Transient expression in nonsteroidogenic cells reveals that the type III isoenzyme specific for male liver does not display oxidative activity for classical substrates of 3 beta-HSD, in contrast to the two other 3 beta-HSD isoenzymes, thus showing exclusively 3-ketosteroid reductase (3 KSR) activity. In order to better understand the sex-specific control of 3 beta HSD activity and type III 3-KSR gene expression in rat liver, we have studied in adult animals of both sexes the effect of sex steroids and hypophysectomy, pituitary implants, PRL, and GH on type III 3-KSR messenger RNA (mRNA) levels and 3 beta-HSD/delta 5-delta 4 isomerase activity as measured by the conversion of [14C]dehydroepiandrosterone into [14C] delta 4-androstenedione. Ribonuclease protection assay using types I-, II-, and III-specific complementary RNA probes reveals that type III transcripts are the only species detectable in liver RNA extracted from intact males, whereas no hybridization signal was detectable with any of the three probes in intact female liver RNA. In males, 15 days after castration, liver type III 3-KSR mRNA levels decreased by 80% compared to intact controls, whereas 3 beta-HSD activity was reduced by 48%. Administration of dihydrotestosterone (DHT) increased by 8.25-fold type III 3-KSR mRNA concentration and completely reversed the inhibitory effect of orchiectomy on 3 beta-HSD activity. In ovariectomized animals, treatment with DHT markedly increased type III 3-KSR mRNA accumulation and 3 beta-HSD activity, thus leading to values similar to those measured in intact males. Simultaneous treatment with 17 beta-estradiol almost completely abolished the stimulatory effect of DHT in female rats, whereas no significant effect was seen in males. Twenty-four days after hypophysectomy, type III 3-KSR mRNA levels were decreased by 50-55% in males, whereas in females these transcripts markedly increased from undetectable to 28-36% of the value measured in intact male rats. Treatment with DHT or 17 beta-estradiol for a period of 9 days starting 15 days after hypophysectomy had no effect in male and female rats. On the other hand, treatment with ovine PRL (1 mg, twice daily) had no effect in males but completely blocked the elevation of type III 3-KSR mRNA levels and 3 beta-HSD activity observed after hypophysectomy in females.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446639 TI - Regulation of androgen receptor expression in the human heterotransplantable prostate carcinoma PC-82. AB - In vivo effects of androgen withdrawal and substitution on human androgen receptor (hAR) expression were evaluated in the androgen-dependent human prostatic carcinoma tumor line PC-82. By application of several antibodies reactive with different epitopes of the hAR molecule, hAR protein expression was studied in tumor transplants by immunohistochemistry and immunoblotting. hAR messenger RNA (mRNA) levels were quantitated in PC-82 tumor tissue with a S1 nuclease protection assay. Most PC-82 tumor cells (> 97%) from testosterone supplemented mice displayed nuclear hAR protein expression immunohistochemically. The almost complete reduction of nuclear hAR immunoreactivity within 5 days after androgen withdrawal (< 10%) was restored after androgen substitution within 1 day. The immunochemical data were confirmed by Western blot analysis. In contrast, no significant changes were observed in hAR mRNA content of PC-82 cells after 5 days of androgen withdrawal. Correlating hAR expression with proliferative activity of PC-82 tumor tissue during endocrine manipulation, a rapid, castration-induced decline of the percentage of bromodeoxyuridine-labeled cells accompanied the loss of hAR. Androgen substitution in castrated male mice restored the proliferative activity. However, this increase of proliferative activity lagged at least 24 h behind the normalization of the hAR protein level. In contrast to the steroid receptor down-regulation by homologous ligands observed in other experimental models, our data support the concept of hAR up regulation by androgen. Since the hAR mRNA content of PC-82 tumor tissue was hardly affected by castration, expression of the hAR in PC-82 is thought to be modulated by translational and/or posttranslational mechanisms. PMID- 1446640 TI - Renal growth hormone receptor gene expression: relationship to renal insulin-like growth factor system. AB - In order to elucidate potential sites of direct GH action on the kidney, we used in situ hybridization to localize GH receptor (GHR) gene expression during the course of development and in the adult rat. In order to illuminate potential interactions between GH and insulin-like growth factor-I (IGF-I) in regulating renal function, we compared the anatomical localization of GHR messenger RNA (mRNA) with that for the IGF-I receptor and for IGF-I in the rat kidney. Low levels of GHR mRNA were present in the kidney from before birth and increased in abundance until postnatal day 40. Hypophysectomy resulted in a decrease and GH treatment resulted in an increase in renal GHR mRNA levels. Renal GHR mRNA was most abundant in the proximal straight tubule, with lesser levels present in the medullary thick ascending limb (MTAL), and it was not detected in the glomerulus or inner medulla. In contrast, IGF-I receptor mRNA was concentrated in the glomerulus, distal nephron and collecting system. The only point of convergence for GHR and IGF-I receptor mRNAs was in the MTAL, where IGF-I mRNA was localized. This segregation of GHR and IGF-I receptor gene expression in the kidney suggests that each hormone has distinct spheres of action along the nephron, with GH acting directly on the proximal straight tubule, whereas IGF-I may act on the glomerulus, distal nephron, and collecting duct. GHR expression in the MTAL, which is the site of renal IGF-I synthesis, supports the view that GH has a direct effect on renal IGF-I synthesis. Finally, it appears that in the kidney, as in other GH-sensitive tissues, GH may regulate its receptor levels. PMID- 1446641 TI - Ouabain as an amplifier of mineralocorticoid-induced hypertension. AB - Ouabain has recently been reported to be an endogenous Na, K-ATPase inhibitor. To evaluate whether it exerts hypertensive action itself or amplifies the hypertensive action of small doses of mineralocorticoids, 5 mg deoxycorticosterone acetate (DOCA), 1 mg ouabain, or a combination of both were injected into mononephrectomized rats weekly for 6 weeks, and changes in blood pressure were evaluated. The blood pressures of control, DOCA-treated, ouabain treated, and the combination treatment group at the sixth week were 138 +/- 3 (SE), 160 +/- 6, 144 +/- 6, and 201 +/- 14 mmHg, respectively. The blood pressure of rats given DOCA or ouabain alone was not significantly different from that of controls. In contrast, the blood pressure of rats given the combination of DOCA and ouabain was significantly higher than that of control rats and those given DOCA or ouabain separately. Cardionephromegaly and histopathological changes found in rats given the combination of DOCA and ouabain were consistent with the effects of an elevation of blood pressure. Further evaluation revealed that the amplification effect of ouabain on the hypertensive action of DOCA was dose dependent, with the minimum dose that caused the amplification effect being 0.25 mg/week. These results indicate that ouabain, although devoid of hypertensive action itself, amplifies the hypertensive action of small doses of DOCA and can cause a hypertensive state similar to that induced by larger doses of DOCA. It is inferred that the amplification effect of ouabain on mineralocorticoids is important in the genesis of hypertension. PMID- 1446642 TI - Characterization of the short isoform of the growth hormone receptor synthesized by rat adipocytes. AB - Two mRNA transcripts that are believed to be alternately spliced products of the GH receptor gene have been reported in a variety of rat tissues. The smaller (1.2 kilobases) transcript was cloned from an adipocyte library, sequenced, and found to encode a protein identical to the soluble GH-binding protein (GHBP) in plasma. An assay that is specific for the short isoform of the GH receptor, often referred to as the GHBP, has been developed using a rabbit antiserum that recognizes the unique amino acid sequence at its carboxyl end. The assay depends upon immunoprecipitation of a complex consisting of [125I]human GH, the binding protein, antiserum, and protein-A cross-linked to agarose beads. To validate the assay, samples of rat plasma were analyzed and found to contain sufficient binding protein to bind 1.46 pmol (32 ng) GH/ml, with an affinity of 2.7 x 10(9) M-1. In adipocyte extracts, binding protein activity was sufficient to bind 61 fmol GH/g tissue, with an affinity of 2.3 x 10(9) M-1. The binding protein was found primarily in the particulate fraction of adipocytes, and it is estimated that adipocytes contain approximately 7000 copies of the binding protein/cell. Only 10% of the binding activity was present in the high speed supernatant of adipocyte homogenates, and soluble binding protein did not appear to be released into the incubation medium when adipocytes were incubated in vitro. A 50 kilodalton (kDa) 35S-labeled protein that may be a glycosylated form of the binding protein was immunoprecipitated from both the soluble and particulate fractions of adipocyte extracts by the antiserum, and addition of the synthetic peptide antigen blocked immunoprecipitation of this protein. A 150-kDa protein in the high speed supernatant fraction was also specifically immunoprecipitated by the antiserum. Although it is unlikely to be a glycosylated form of the binding protein, it may cross-react with the antiserum or perhaps be coprecipitated, because it interacts with the binding protein. In addition, 38- and 42-kDa bands were specifically immunoprecipitated from the detergent-treated particulate fraction of adipocyte extracts that were enriched for the binding protein by adsorption to immobilized GH. We conclude that 1) adipocytes synthesize the short isoform of the GH receptor, and that this protein is primarily associated with a membrane fraction of the cells; and 2) the GHBP expressed in adipocytes is not released into the incubation medium and differs in size from the GHBPs in rat plasma.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446643 TI - Characterization of epidermal growth factor in mouse testis. AB - Considerable evidence exists to suggest that epidermal growth factor (EGF) influences spermatogenesis directly. The tissue source of this EGF, however, is not yet clear. In this study we examine whether the testis itself can serve as a source of EGF. Gel filtration fractions of acid extracted testes exhibited the ability to displace 125I-EGF from testis membranes. The testicular fractions containing the 125I-EGF displacement activity coeluted within the same range as those of submandibular gland (SG) fractions containing mature EGF and prepared in an identical fashion. Next, we employed specific antisera probes to investigate first, whether the testis synthesizes this EGF displacement activity and second, to determine the cell distribution of the testicular EGF. Two types of antisera probes were employed: 1) commercially available antisera to mature EGF (EGFm), i.e. the 6,000 M(r) peptide, and 2) polypeptide specific antisera to the C terminus of the EGF precursor (EGFp), i.e. the 140,000 M(r) integral membrane molecule which exhibits seven EGF-like repeats in addition to the EGFm. Metabolic labeling of testis with 35S-methionine was performed, followed by immunoprecipitation with the anti-EGFm antisera. Parallel studies using kidney and SG were used as positive controls. Fluorograms exhibited a prominent band at M(r) 140,000 for testis and kidney, corresponding to the EGFp. There was, in addition, a M(r) 50,000 band present for the testis. In SG, a band at M(r) 6,000, corresponding to EGFm, in addition to bands at M(r) 21,000 and 46,000 were observed also. Immunoblotting of testis, kidney, and SG membrane preparations with the specific antisera to either the EGFm or EGFp also resulted in identifying the EGFp at M(r) 140,000, as well as other lower mol wt bands. Preadsorption of anti-EGFm antisera with excess EGFm eliminated all of the specific bands that were immunoblotted. Peroxidase immunocytochemistry of testis, kidney, and SG was also performed using the specific antisera to either EGFm or EGFp. EGFp and EGFm staining in SG and kidney was identical to previously published results in which the distribution of EGFm in these tissues was established. In testis, EGFm immunostaining showed positive results in Sertoli cells, pachytene spermatocytes and round spermatids. In contrast, EGFp immunostaining was limited to pachytene spermatocytes and round spermatids. These results suggest that the testis must now be included in the list of tissues capable of synthesizing EGFp. Specifically, EGFp synthesis appears limited to the post meiotic germ cells. PMID- 1446644 TI - Insulin-like growth factor-II (IGF-II) messenger ribonucleic acid is expressed in steroidogenic cells of the developing ovine adrenal gland: evidence of an autocrine/paracrine role for IGF-II. AB - Insulin-like growth factors (IGFs) are potent mitogenic and differentiation promoting factors that regulate the growth and development of many fetal tissues. Their role in the development of the adrenal gland and activation of its function is not known. The latter is crucial in providing the stimulus for the maturation of various fetal organs and determines the onset of parturition in sheep. To examine the hypothesis that IGFs are important autocrine/paracrine regulators of fetal adrenal development in vivo, we localized IGF-I and IGF-II mRNAs and peptides in the adrenal glands of developing sheep fetuses and correlated the cellular distribution with localization of 3 beta-hydroxysteroid dehydrogenase, tyrosine hydroxylase, and phenylethanolamine-N-methyltransferase enzymes by immunohistochemistry. Adrenal glands from 60- to 75-day-old (n = 4), 100- to 110 day-old (n = 4), 120- to 130-day-old (n = 4), and 145- to 147-day-old (term; n = 4) fetal sheep and 1- to 4-day-old newborn lambs (n = 4) were dissected and either snap-frozen or fixed. Total RNAs were subjected to Northern analysis using ovine IGF-I and IGF-II cDNA probes. Seven IGF-II transcripts of 1.2-6.0 kilobases (kb) were identified in the adrenal glands of fetuses at all gestational ages, and in the newborn. By densitometry, the abundance of IGF-II mRNA was highest in the fetal adrenal gland at 60 days, decreased slightly between 60 and 100 days, remained relatively constant until term, and decreased significantly after birth. At all gestational ages, IGF-II mRNA was detectable in significantly greater abundance than IGF-I mRNA. IGF-I and IGF-II mRNAs were localized by in situ hybridization using 35S-labeled anti-sense cRNA probes, and the peptides by immunohistochemistry using specific antisera. Low levels of IGF-I mRNA were detected in the zona fasciculata, but not in the zona glomerulosa. There was strong hybridization of the IGF-II cRNA to the zona glomerulosa and fasciculata and to the capsule. The hybridization signal was greater in the zona fasciculata than in the zona glomerulosa. IGF-II mRNA was also detected in groups of cells within the medulla. Localization of IGF-II mRNA by in situ hybridization correlated well with the distribution of IGF-II immunoreactivity and with 3 beta hydroxysteroid dehydrogenase-positive cells in the cortex and in groups of cells within the medulla.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1446645 TI - Establishment of a folliculo-stellate-like cell line from a murine thyrotropic pituitary tumor. AB - An isologously transplantable mouse thyrotropic pituitary tumor (TtTb) that had been induced by radiothyroidectomy was found to form lobules composed of parenchymal glandular cell elements. The surfaces of these lobules were covered by stellate cells bearing long processes that gave a strong immunopositive reaction with a specific antiserum against glial fibrillary acidic protein (GFAP). GFAP was also positive in pituitary folliculo-stellate cells (FS cells). Since in the anterior pituitary gland, no other cellular component showing positive staining with anti-GFAP antibody was observed, it seems probable that the GFAP-positive cells in the thyrotropic tumor are related to the FS cells in the anterior pituitary. Upon cultivation of the thyrotropic tumor, cells with long processes appeared. These cells showed strong staining for GFAP and were dependent on basic fibroblast growth factor for cell growth. By repeated passage, the GFAP-positive cells became a stably growing immortal cell line, which was tentatively named TtT/GF. Since the characteristics of TtT/GF were similar to those of FS cells in the anterior pituitary, i.e. the presence of many lysosomes and numerous intermediate filaments in the cytoplasm, phagocytic activity, follicle formation, and GFAP and S-100 protein positivity, we suggest that TtT/GF cells are derived from pituitary FS cells. PMID- 1446646 TI - In vitro ligand binding of 125I-recombinant human activin A to the female rat brain. AB - Activin has been localized within cells and terminals in the brain. However, little is known about the site of action of this hormone within the brain. In the present study in vitro ligand autoradiography was used to determine the distribution of high affinity binding sites for 125I-rh activin A in rat brain. The highest density of binding sites were concentrated in the amygdala and other forebrain limbic structures. Binding was saturable in selected amygdala nuclei with an apparent Kd of approximately 0.2 nM. 125I-rh activin A binds specifically in regions known to contain terminals immunoreactive for this hormone, and also at sites distinct from the location of activin A containing neuronal terminals (e.g. the ventral limbic system). PMID- 1446647 TI - Nuclear localization and hepatic zonation of rat "spot 14" protein: immunohistochemical investigation employing anti-fusion protein antibodies. AB - S14 protein and mRNA levels are rapidly regulated by hormones and diet. We have purified a 45-Kd fusion protein from lysates of transformed E. coli that includes the entire S14 polypeptide. Affinity-purified rabbit anti-fusion protein antibodies were used in immunohistochemistry to determine the distribution of S14 protein across the hepatic lobule, and to reassess its intracellular location. In hyperthyroid liver, S14 protein clustered near the central venous zone, and was not detectable in the periportal area of the acinus. The signal in perivenous hepatocytes was primarily nuclear in location, in stark contrast to previous subcellular fractionation studies. Visualization of identical hepatic distribution and subcellular localization employing anti-synthetic peptide antiserum provided evidence for the specificity of the immunostaining, as did attenuation of the signal by preincubation of the antibody with its antigen. No staining was observed in sections of heart or hypothyroid liver, as expected from the low levels of S14 protein in those tissues. The data indicate that induction of S14 protein expression by T3 occurs through enhanced expression by perivenous hepatocytes, rather than by recruitment of cells in more peripheral zones of the lobule. Nuclear localization of the S14 protein by immunohistochemistry suggests that it is lost from nuclei during standard fractionation procedures, and prompts consideration of a role for S14 in regulation of nuclear structure and/or function. PMID- 1446648 TI - Ultrastructural evidence for a paracrine regulation of the rat adrenal cortex mediated by the local release of catecholamines from chromaffin cells. AB - The adrenal glands of perfusion fixed rats were investigated by light and electron microscopy. Within the rat adrenal cortex occurred rays and islets of chromaffin cells which were in close contacts with cortical cells on the electron microscopical level. We achieved to catch the process of exocytosis from a chromaffin cell located within the zona glomerulosa in direct apposition with an adrenocortical cell. The documentation of an exocytotic process from a chromaffin cell neighbouring a cortical cell provides direct evidence in support of a paracrine regulation of the cortex mediated by chromaffin cells. PMID- 1446649 TI - Effect of a phorbol ester on immunoreactive endothelin-1 release from cultured porcine aortic endothelial cells. AB - This study was designed to examine how protein kinase C (PKC) regulates the release of endothelin-1 (ET-1) from cultured porcine aortic endothelial cells. We measured the release of immunoreactive (IR)-ET-1 from cells cultured for up to 72 h in the presence or absence of a phorbol ester TPA. The release of IR-ET-1 from control cells (no TPA) increased according to time for up to 72 h. In the presence of TPA, the release of IR-ET-1 from the cells was higher than the control level for up to 8 h, but was lower thereafter and reached a plateau after 48 h. TPA dose-dependently stimulated IR-ET-1 release during incubation for 4 h, but suppressed it after incubation for 72 h. Stimulation of PKC by diacylglycerol mimicked the early (4 h) action of TPA. On the other hand, pretreatment of cells with TPA to downregulate PKC significantly suppressed basal and thrombin- or FCS stimulated IR-ET-1 release. These findings suggest that the activation of PKC is related to the stimulation of ET-1 release and that down-regulation of PKC leads to the suppression of ET-1 release from cultured endothelial cells. PMID- 1446650 TI - Type A-insulin resistance with lipopexia on extremities: a case report. AB - We present the unusual case of a 17-year-old female with insulin-resistant diabetes, acanthosis nigricans, hirsutism, amenorrhea, dental dysplasia and lipopexia on the extremities. She had been diagnosed as having border line diabetes with hyperinsulinemia at age 12 when she was not obese and diabetes mellitus at age 13. On admission, she was obese and had lipopexia only on the extremities. The presence of hyperinsulinemia and poor response to exogenous insulin suggested severe insulin resistance. Insulin binding to transformed B lymphoblasts derived from her was extremely low compared to the normal control, showing decreased receptor affinity. Her parents and sister exhibited hypersecretion of insulin in response to a 75 g oral glucose tolerance test. Her mother was diabetic, and her father and sister had border line diabetes, whereas her brother had a normal response. These findings support strongly the diagnosis of a type A syndrome with severe insulin resistance associated with lipopexia on the extremities. A genetic defect in the insulin receptor gene may be responsible. PMID- 1446651 TI - Differences in pathological findings and growth hormone responses in patients with growth hormone-producing pituitary adenoma. AB - Plasma growth hormone (GH) responses to various stimuli were examined in 21 patients with GH-producing pituitary adenomas, classified into three types by the immunohistochemistry of cytokeratin and the glycoprotein hormone alpha-subunit distribution. Seven type 1 adenomas were exclusively composed of cells in which the cytokeratin formed a dot-like pattern; they were chromophobic to hematoxylin and eosin (H&E), occasionally positive for GH, and almost completely negative for the alpha-subunit. Thirteen type 2 adenomas were composed of cells with cytokeratin that had a perinuclear distribution; they were eosinophilic to H&E, and diffusely positive for both GH and the alpha-subunit. One patient had a type 3 adenoma which had a mixed pattern of intracellular cytokeratin distribution and was chromophobic and eosinophilic to H&E. Clinically, type 1 is characterized by earlier onset, larger tumor size, and more frequent aggressive extension. Paradoxical GH responses to TRH and OGTT were seen in 1 of 6 patients (16.7%) of type 1 and 8 of 9 patients (88.9%) of type 2, and 0% of type 1 and 62.5% of type 2, respectively. Type 2 cases showed higher plasma GH response to GH-releasing hormone, and a tendency to greater suppression of plasma GH by bromocriptine compared with type 1. Octreotide acetate administration revealed that the nadir/basal ratio of plasma GH levels was 42.9 +/- 6.6% in type 1 and 13.5 +/- 5.8% in type 2. These results suggest that there is a pathophysiological difference between these two distinct types of GH-producing pituitary adenomas. PMID- 1446652 TI - Translation of rat ovarian mRNA to two 20 alpha-hydroxysteroid dehydrogenase isozymes in Xenopus oocytes. AB - 20 alpha-Hydroxysteroid dehydrogenase (20 alpha-HSD) in rat luteal tissue catalyzes the conversion of progesterone into a biologically inactive steroid, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OHP) and depletes the output of progesterone into the circulation. An increase in 20 alpha-HSD activity in luteal tissue is therefore a prerequisite for the regression of functional corpora lutea in rats. We have reported that ovarian 20 alpha-HSD is composed of two isoforms (HSD1 and HSD2). In this study, among batches of ovaries collected randomly during the estrous cycle, we selected two batches (batches A and B): the cytosol preparation from batch A contained both HSD1 and HSD2 activities, whereas that from batch B contained only HSD1 activity. From these 2 batches, we extracted mRNA, and each mRNA preparation was subjected to translation in Xenopus oocytes. The translation products of batch A exhibited both HSD1 and HSD2 activities, and those of batch B only HSD1 activity in accordance with the enzymatic activities observed in the respective cytosolic preparations. The results are compatible with the presence of two distinct mRNAs coding HSD1 and HSD2, and if so their transcription will be regulated separately according to the functional state of the ovary. PMID- 1446653 TI - Thyrotoxicosis with low serum total T3 level in patients with destructive thyroiditis and non-thyroidal illness. AB - The serum total T3 level, evaluated in 687 patients with thyrotoxicosis diagnosed by an elevated serum free T4 level and suppressed serum TSH level, was found to be high in 98.1% and normal in 1.9% of 592 patients with Graves' hyperthyroidism, and high in 75.8%, normal in 21.1% and low in 3.2% of 95 patients with destructive thyroiditis. Non-thyroidal illness was found in about a third of the patients with thyrotoxicosis and a normal serum total T3 level. The serum total T3 level was low with elevated serum thyroglobulin and reverse T3 levels in three patients with severe non-thyroidal illness, in whom the thyroidal radioactive iodine uptake was suppressed and the thyrotoxicosis resolved spontaneously with a normalization of the serum total T3 level after recovery from the destructive thyroiditis and non-thyroidal illness. It is therefore concluded that thyrotoxicosis with a low serum total T3 level, partially due to associated non thyroidal illness, is more frequently found in patients with destructive thyroiditis than in those with Graves' hyperthyroidism. PMID- 1446654 TI - Insulin dependent diabetes mellitus accompanied by nephrocalcinosis and renal failure. AB - Renal failure was found in a five-year-old patient who had been treated with insulin since he was diagnosed as having insulin dependent diabetes mellitus (IDDM) at 3 years of age. Laboratory data showed that his renal failure was caused by a renal tubular dysfunction. The autopsy findings of his pancreas were compatible with those of IDDM. The kidneys were atrophied with an innumerable number of crystals in the proximal tubuli. Staining by Kossa indicated that the crystals contained calcium salt. The calcium content of his kidneys was significantly higher than that of control. The nephrocalcinosis seems to be caused by hypercalciuria associated with IDDM. PMID- 1446655 TI - Resolution of possible paradoxical responses of gonadotropins to thyrotropin releasing hormone with bromocriptine therapy in a patient with follicle stimulating hormone-secreting pituitary adenoma. AB - We report the effectiveness of bromocriptine therapy in resolving the abnormal responses of plasma FSH and LH to TRH in a 70-year-old male with FSH-secreting pituitary macroadenoma who had unsuccessful transsphenoidal pituitary surgery. In the pre-treatment and post-operative periods, respectively, basal plasma levels of FSH were increased to 88.7 and 65.6 mIU/ml (normal range; 8.5-32.4) but those of plasma LH were normal being 7.0 and 4.1 mIU/ml; (normal range; 4.1 to 14.0). The responses of plasma FSH and LH to LHRH were exaggerated and their paradoxical responses to TRH were highly suggested. During the bromocriptine therapy, the basal level of plasma FSH was normalized and that of plasma LH remained normal. The magnitude of FSH and LH responses to LHRH decreased and their paradoxical responses to TRH were completely resolved. PMID- 1446656 TI - Pre-Cushing's syndrome: a case report. AB - A 67-year-old man affected by prostate cancer was incidentally found to have a nodular enlargement of the left adrenal gland without apparent changes in hormonal status. The adrenal mass was found to be scintigraphically active, the radiolabelled compound being concentrated in its context with a consensual suppression of the contralateral uptake. The patient underwent a resection of the adrenal tumor. Histologically and biochemically, the adrenal mass was found to be a non-functioning adenoma. The radioisotopic uptake along with the non-hormonal activity prompted us to call this tumor "Pre-Cushing's syndrome" of the adrenal cortex. PMID- 1446657 TI - Thyrotropin-secreting pituitary adenoma: a case report. AB - We report a 44-year-old male with a thyrotropin (TSH)-secreting pituitary adenoma. Based serum free triiodothyronine (FT3, 12.1 pmol/l) and free thyroxine (FT4, 28 pmol/l) were increased with normal basal TSH (3.1 mU/l). There was impaired TSH response to thyrotropin releasing hormone (TRH) test. Serum TSH was suppressed to 59% of the basal level after oral administration of 1.4 mg 3,3'-5 triiodothyroacetic acid (triac), whereas no suppression was observed after 75 micrograms daily administration of triiodothyronine (T3). Serum concentrations of alpha-subunit of TSH (TSH-alpha) and TSH-alpha/TSH molar ratio were high, being 1.95 micrograms/l, and 4.4, respectively. Pituitary CT and MRI scan showed the presence of a macroadenoma in the anterior lobe of the pituitary gland. Histopathology of the excised pituitary confirmed the diagnosis of a TSH producing adenoma. A positive correlation between TSH and FT3 (r = 0.66, P less than 0.01) or FT4 (r = 0.54, P less than 0.01) was observed in serial sera obtained before and after operation. PMID- 1446658 TI - Binding of thyrotropin to lentil lectin is unchanged by thyrotropin-releasing hormone administration in three patients with thyrotropin-producing pituitary adenomas. AB - Glycoproteins have increased affinity for lentil lectin when fucose residues are bound to N-acetylglucosamine in the "core region" of their asparagine-linked oligosaccharides. In three patients with thyrotropin (TSH)-producing pituitary tumors, the proportion of serum TSH isoforms that bound to lentil (70.8% +/- 15%) was higher than that seen for TSH from normal persons (32.5 +/- 8%). Unlike normal subjects, the concentration of TSH circulating in the tumor patients after acute administration of TSH-releasing hormone (TRH) did not rise, and the TSH did not exhibit increased binding to lentil compared to basal TSH. The TSH binding to lentil in one tumor patient decreased after metoclopramide, but TSH binding to lentil generally remained unchanged after metoclopramide or L-dopa administration. We conclude that human thyrotropic tumor tissue, unlike normal thyrotrophs, generally fails to release more highly fucosylated isoforms of TSH after pharmacologic stimulation, perhaps because the tumor tissue is less readily modulated by endocrine stimuli, or because the TSH is already relatively highly fucosylated. PMID- 1446659 TI - Testosterone regulates epidermal growth factor levels in the thyroid gland of hypothyroid mice. AB - The effects of testosterone (TP) and thyroxine (T4) on the level of epidermal growth factor (mEGF) in the thyroid were compared in a hypothyroid mouse model. Groups of five adult female BALB/c mice were given a "severe" hypothyroid regimen consisting of an iodine deficient diet together with oral and s.c propylthiouracil (PTU). Sialoadenectomy or sham operation was performed after 18 days on the hypothyroid regimen. The mice convalesced on normal diet for 5 days and beginning from day 23 received either T4, 1 ug/g or 2 ug/g, s.c daily or TP, 0.3 mg or 0.75 mg, i.m. every third day until day 33, while continuing the hypothyroid regimen. Control mice received normal diet and vehicles for the various injections. The mice were killed on day 33 and thyroidal EGF levels determined by radioimmunoassay. The mean+S.E. levels of mEGF in the thyroid were 10.12 +/- 1.75 ng/mg protein (control), 3.82 +/- 0.67 ng/mg (hypothyroid; p < 0.01), 3.07 +/- 1.52 (T4, 1 ug/g; p < 0.02), 2.59 +/- 0.46 ng/mg (T4, 2 ug/g; p < 0.01), 8.58 +/- 2.48 (TP, 0.3 mg), and 9.65 +/- 1.86 (TP, 0.75 mg). Thus thyroidal mEGF levels decreased significantly in all groups except those subsequently treated with testosterone; T4 was ineffective in reversing the tissue depletion of mEGF in this model. These results show that mEGF levels in the thyroid could be depleted by hypothyroidism and may also be androgen responsive. PMID- 1446660 TI - Vasoactive intestinal peptide enhances thyroidal iodide uptake during dietary iodine deficiency. AB - The presence of vasoactive intestinal peptide and neuropeptide Y in thyroid nerves and their effects on thyroid blood flow are well known. However, the effects of these two neuropeptides on the various processes involved in thyroid hormone biosynthesis and release have not been fully explored. We have now tested these two peptides for effects on an early step in thyroid hormone biosynthesis, namely iodide uptake, a process which is comprised of trapping and organification. In these experiments, we have used anesthetized adult male rats pretreated with thyroxine or fed a low iodine diet to increase thyroidal sensitivity. Vasoactive intestinal peptide significantly increased iodide uptake in rats fed an iodine deficient diet but not in those fed a normal iodine diet. This effect disappeared if animals were pretreated with propylthiouracil. Neuropeptide Y did not alter iodide uptake in rats on either the low or the high iodine diet, regardless of the presence or absence of propylthiouracil. The effect of vasoactive intestinal peptide on iodide uptake could be due to its influence on the organification of iodine, or on thyroid blood flow, or on both processes. PMID- 1446661 TI - Detection of albumin binding abnormalities in sera of patients with familial dysalbuminaemic hyperthyroxinaemia using isoelectric focusing. AB - Definitive diagnosis of familial dysalbuminaemic hyperthyroxinaemia (FDH) requires finding a high concentration of [125I]T4 bound to albumin. We used isoelectric focusing (IEF) in agarose gels to study the sera of three members of a family with FDH and compared the distribution of [125I]T4 obtained by IEF with that obtained by conventional agarose gel electrophoresis (AGE). Both IEF and AGE confirmed the diagnoses of FDH. In case #1, the % [125I]T4 bound to albumin was 15.2 and 20.0, with IEF and AGE, respectively, in case #2 23.6 and 26.5, and in case #3, 22.1 and 23.0, compared to normal controls of 5.9 and 7.4, respectively. IEF has not previously been used to diagnose FDH, to our knowledge. IEF has the advantage of eliminating TBG interference with albumin migration, which can potentially complicate the diagnosis of FDH when the AGE method is used. To date, reverse flow electrophoresis, a more cumbersome method with poorer resolution than IEF, has been utilized to eliminate TBG interference. IEF, in agarose gels, is a relatively simple and accurate method to diagnose FDH, and avoids artifacts which may be encountered with AGE. PMID- 1446662 TI - A point mutation of low-density-lipoprotein receptor causing rapid degradation of the receptor. AB - The exons of the low-density-lipoprotein-(LDL)-receptor gene from a Japanese patient with homozygous familial hypercholesterolemia were amplified by the polymerase chain reaction (PCR), and their nucleotide sequences were determined. A point mutation from G to C was found in exon 9, which was expected to change Asp at position 412 to His. This amino acid change occurred within the epidermal growth-factor-precursor homology domain of the LDL receptor, slightly impairing the processing from the precursor to the mature form and causing rapid degradation of the mature form in the fibroblasts of the patient. The mutant LDL receptor gene transfected into COS-1 cells expressed a LDL-receptor protein with the same properties as the protein expressed in the fibroblasts of the patient; impaired processing and rapid degradation of the synthesized receptor protein. The mutation was identified in family members of the patient by dot-blot hybridization of PCR-amplified DNA with the mutant oligonucleotide. The family members carrying the mutant gene showed higher serum cholesterol levels than the others. However, their cholesterol levels were also greatly influenced by the apolipoprotein-E phenotype. PMID- 1446663 TI - Investigation of the mechanism of non-turnover-dependent inactivation of purified human 5-lipoxygenase. Inactivation by H2O2 and inhibition by metal ions. AB - Human 5-lipoxygenase is a non-heme iron protein which is reported to be highly unstable in the presence of oxygen. The results of this investigation demonstrate that H2O2 generated during air oxidation of thiols is the main factor in non turnover-dependent inactivation of purified recombinant human 5-lipoxygenase for the following reasons: catalase protects against oxygen-dependent inactivation of the enzyme in the presence of dithiothreitol; the active, stable enzyme can be prepared under aerobic conditions with the exclusion of dithiothreitol and contaminating metal ions; 10 microM H2O2 causes the rapid inactivation of the enzyme. The native (ferrous) enzyme is approximately seven times more sensitive to inactivation by H2O2 than the ferric enzyme, suggesting that the mechanism of inactivation involves a Fenton-type reaction of the ferrous enzyme with H2O2, resulting in the formation of an activated oxygen species. Purification of 5 lipoxygenase under aerobic conditions (no dithiothreitol) results in an increase in both the specific activity of the purified protein [up to 70 mumol 5(S) hydroperoxy-6-trans-8, 11, 14-cis-icosatetraenoic acid (5-HPETE)/mg protein] and in the ratio of specific activity to enzyme iron content compared to enzyme purified under anaerobic conditions in the presence of dithiothreitol. The reaction of the highly active 5-lipoxygenase enzyme shows a dependence on physiological intracellular calcium concentrations, half-maximal product formation being obtained at 0.9 microM free Ca2+. The maximal enzyme activity is also dependent on EDTA and dithiothreitol and low amounts of carrier protein, as well as the known activators PtdCho and ATP. Ca2+ can be substituted by Mn2+, Ba2+ and Sr2+, although lower levels of stimulation are obtained. 5-Lipoxygenase is strongly inhibited by low concentrations (< or = 10 microM) of Zn2+ and Cu2+. The inhibition by Cu2+ is apparently irreversible, whereas that by Zn2+ is slowly reversed (t1/2 = 2 min) in the presence of excess EDTA. These observations on the mechanism of non-turnover-dependent inactivation of 5-lipoxygenase, and the optimisation of assay conditions, have facilitated the purification of large quantities of relatively stable enzyme that will be useful for further kinetic and physical studies. PMID- 1446664 TI - Nuclear-magnetic-resonance analysis of the capsular antigen of Actinobacillus pleuropneumoniae serotype 9. Its identity with the capsular antigen of Escherichia coli K62 (K2ab), Neisseria meningitidis serogroup H and Pasteurella haemolytica serotype T15. AB - The specific capsular antigen of Actinobacillus pleuropneumoniae serotype 9 was characterized by one-dimensional and two-dimensional high-field nuclear-magnetic resonance methods, and by chemical analyses, as a teichoic-acid-type polymer of a repeating unit having the structure [formula: see text] The basic polymer structure is identical to capsular antigens of Neisseria meningitidis group H, Escherichia coli K62 (K2ab) and Pasteurella haemolytica serotype T15. PMID- 1446665 TI - The 70-kilodalton heat-shock proteins of the SSA subfamily negatively modulate heat-shock-induced accumulation of trehalose and promote recovery from heat stress in the yeast, Saccharomyces cerevisiae. AB - In the yeast, Saccharomyces cerevisiae, the disaccharide trehalose is a stress related metabolite that accumulates upon exposure of cells to heat shock or a variety of non-heat inducers of the stress response. Here, we describe the influence of mutations in individual heat-shock-protein genes on trehalose metabolism. A strain mutated in three proteins of the SSA subfamily of 70-kDa heat-shock proteins (hsp70) overproduced trehalose during heat shock at 37 degrees C or 40 degrees C and showed abnormally slow degradation of trehalose upon temperature decrease from 40 degrees C to 27 degrees C. The mutant cells were unimpaired in the induction of thermotolerance; however, the decay of thermotolerance during recovery at 27 degrees C was abnormally slow. Since both a high content of trehalose and induced thermotolerance are associated with the heat-stressed state of cells, the abnormally slow decline of trehalose levels and thermotolerance in the mutant cells indicated a defect in recovery from the heat stressed state. A similar albeit minor defect, as judged from measurements of trehalose degradation during recovery, was detected in a delta hsp104 mutant, but not in a strain deleted in the polyubiquitin gene, UB14. In all our experiments, trehalose levels were closely correlated with thermotolerance, suggesting a thermoprotective function of trehalose. In contrast, heat-shock proteins, in particular hsp70, appear to be involved in recovery from the heat-stressed state rather than in the acquisition of thermotolerance. Cells partially depleted of hsp70 displayed an abnormally low activity of neutral trehalase when shifted to 27 degrees C after heat shock at 40 degrees C. Trehalase activity is known to be under positive control by cAMP-dependent protein kinases, suggesting that hsp70 directly or indirectly stimulate these protein-kinase activities. Alternatively, hsp70 may physically interact with neutral trehalase, thereby protecting the enzyme from thermal denaturation. PMID- 1446666 TI - Amino acid and DNA sequences of an extracellular basic protease of Dichelobacter nodosus show that it is a member of the subtilisin family of proteases. AB - A DNA fragment encoding an extracellular basic protease (pI approximately 9.5) from Dichelobacter nodosus, a Gram-negative obligate anaerobe and the causative agent of ovine footrot, has been cloned and expressed in Escherichia coli and sequenced. E. coli harbouring a plasmid with a 3-kb DNA fragment containing the D. nodosus basic-protease gene exhibited proteolytic activity when tested on skim milk plates. The sequence of the native basic protease isolated from D. nodosus was also determined by direct amino acid sequencing. Comparison of the deduced sequence of the primary translation product (603 residues) and that of the native protease (344 residues) indicates that the protease is synthesized as a precursor molecule, containing a signal peptide (21 residues), a 111 amino acid pro-peptide and a 127 residue C-terminal extension which is subsequently processed to the mature active form. Comparison of the D. nodosus basic protease sequence with that of other serine proteases showed that it is related to the subtilisin family of proteases with strong conservation of sequence identity around the catalytic site residues. A remarkable similarity in structure was found to the serine protease of Xanthomonas campestris, a plant pathogen, with respect to the length of the precursor segments, conservation of disulfide bridges and approximately 50% sequence identity of the mature proteases. PMID- 1446667 TI - Protection by glutathione and other thiol compounds against the loss of protein thiols and tocopherol homologs during microsomal lipid peroxidation. AB - Microsomes from rat liver were used to investigate the mechanisms by which thiol compounds protect cellular membranes against damage from oxidants. Glutathione (GSH), dihydrolipoate and dithioerythritol, but not cysteine, ameliorated the loss of thiol groups of microsomal proteins attacked by Fe/ADP/NADPH or Fe/ADP/ascorbate prooxidant systems. The protection by GSH, but not dihydrolipoate or dithioerythritol, appeared to be enzymic since it was lost after microsomes were heated or treated with trypsin. The blocking of microsomal protein thiols with N-ethylmaleimide also diminished the protective effect of GSH. Lipid peroxidation, as assessed by chemiluminescence and vitamin-E loss, was inhibited in parallel with the protection of protein thiols. In microsomes lacking vitamin E, the protection of protein thiols by exogenous thiols was diminished. However, the GSH-dependent protection of vitamin E showed no preference for alpha-tocopherol over other tocopherol homologs. It is suggested that a GSH-dependent enzyme maintains protein thiols in the face of oxidative damage during microsomal peroxidation. A maintenance of protein thiols might not only protect important metabolic functions, but may also afford an antioxidant capacity to membranes, and account for one facet of the GSH-dependent inhibition of lipid peroxidation. PMID- 1446668 TI - Control of the metabolic flux in a system with high enzyme concentrations and moiety-conserved cycles. The sum of the flux control coefficients can drop significantly below unity. AB - In a number of metabolic pathways enzyme concentrations are comparable to those of substrates. Recently it has been shown that many statements of the 'classical' metabolic control theory are violated if such a system contains a moiety conserved cycle. For arbitrary pathways we have found: (a) the equation connecting coefficients CEiJ (obtained by varying the Ei concentration) and CviJ (obtained by varying the kicat), and (b) modified summation equations. The sum of the enzyme control coefficients (equal to unity under the 'classical' theory) appears always to be below unity in the systems considered. The relationships revealed were illustrated by a numerical example where the sum of coefficients CEiJ reached negative values. A method for experimental measurements of the above coefficients is proposed. PMID- 1446669 TI - Interleukin-1 beta and transforming growth factor-beta 2 enhance cytosolic high molecular-mass phospholipase A2 activity and induce prostaglandin E2 formation in rat mesangial cells. AB - Interleukin-1 beta induces gene expression and secretion of group-II phospholipase A2 and release of prostaglandin E2 from rat mesangial cells. The interleukin-1 beta-induced synthesis of group-II phospholipase A2 is prevented by transforming growth factor-beta 2, whereas transforming growth factor-beta 2 potentiated the interleukin-1 beta-evoked prostaglandin E2 production. Transforming growth factor-beta 2 itself did not induce synthesis of group-II phospholipase A2, although it stimulated prostaglandin E2 formation. Here we describe the effect of interleukin-1 beta and transforming growth factor-beta 2 on a cytosolic phospholipase A2 activity and prostaglandin E2 formation in rat mesangial cells. Based on the resistance to dithiothreitol and migration profiles on a Mono-Q anion-exchange column and a Superose 12 gel-filtration column, the cytosolic phospholipase A2 activity was assigned to a high-molecular-mass phospholipase A2. Measured with 1-stearoyl-2-[1-14C]arachidonoylglycero phosphocholine as substrate, both interleukin-1 beta and transforming growth factor-beta 2 enhanced the high-molecular-mass phospholipase A2 activity. The stimulation of rat mesangial cells with interleukin-1 beta and transforming growth factor-beta 2 was time- and dose-dependent with maximal cytosolic phospholipase A2 activities at 10 nM and at 10 ng/ml respectively, after 24 h of stimulation. Under these conditions, interleukin-1 beta and transforming growth factor-beta 2 enhanced the cytosolic phospholipase A2 activity 2.2 +/- 0.6-fold and 2.5 +/- 0.6-fold, respectively. These results strongly suggest that an enhanced cytosolic high-molecular-mass phospholipase A2 activity is involved in the formation of prostaglandin E2 mediated by transforming growth factor-beta 2. Whether interleukin-1 beta induced group-II phospholipase A2 and/or interleukin-1 beta-enhanced cytosolic phospholipase A2 activity is involved in prostaglandin E2 formation in rat mesangial cells is discussed. PMID- 1446670 TI - Isolation and functional analysis of histidine-tagged elongation factor Tu. AB - The study of the structure/function relationships of the Escherichia coli elongation factor Tu (EF-Tu) via mutagenesis has been hampered by difficulties encountered in separating the mutated factor from other proteins, in particular native EF-Tu. Here we describe a novel system for the purification of EF-Tu mutant species, based on metal-ion affinity chromatography. To facilitate rapid and efficient purification we designed a recombinant EF-Tu with an additional C terminal sequence of one serine and six histidine residues. A cell extract containing the His-tagged EF-Tu (EF-TuHis) is applied to a Ni(2+) nitrilotriacetic acid column. EF-TuHis can be selectively eluted with an imidazole containing buffer, yielding a preparation of more than 95% purity, free of wild-type EF-Tu. In-vitro and in-vivo functional analyses show that EF-TuHis resembles the wild-type EF-Tu, which makes this one-step isolation procedure a promising tool for the study of the interactions of mutant EF-Tu with the various components of the elongation cycle. The new isolation procedure was successfully applied for the purification of a mutant EF-TuHis with a Glu substitution for Lys237, a residue possibly involved in the binding of aminoacyl-tRNA. PMID- 1446671 TI - Synthetic peptides as antagonists of the anaphylatoxin C3a. AB - Peptide compounds resembling the receptor-binding C-terminal domain of the anaphylatoxic peptide C3a were synthesized to examine two kinds of C3a antagonism: (a) specific desensitization of C3a-sensitive cells and (b) competitive binding to the C3a receptor. We used guinea-pig platelets, which express a C3a receptor and specifically release ATP upon stimulation, to evaluate the actions of the C3a analogues. The ATP liberation can be inhibited by pretreatment (i.e. desensitization) of the guinea-pig platelets with substimulatory concentrations of C3a or its analogues. Compared to C3a, several peptides were found with at least a tenfold greater difference between the required concentrations for C3a-specific half-maximal desensitization (DD50) and half-maximal platelet activation (ED50). The most potent compounds were YAAALKLAR and Fmoc-EAALKLAR (Fmoc: 9-fluorenylmethoxycarbonyl) with an ED50/DD50 of 140 +/- 28 and 80 +/- 17, respectively (mean +/- standard deviation). The ED50/DD50 of human C3a was found to be only 6 +/- 2. Some C3a derivatives were also tested in competitive binding studies for their ability to compete with C3a for receptor sites on guinea-pig platelets. Three of them were considered partial antagonists [YRRGRCGGLCLAR, YRRGRXCGGLCLAR and YRRGRXCGALCLAR (X = 6-aminohexanoyl)] because their Ki were smaller than their ED50 (Ki/ED50 = 0.6 +/- 0.3, 0.5 +/- 0.1 and 0.4 +/- 0.2, respectively). Interestingly, the last two compounds also had ED50/DD50 values greater than 60. Common to all three peptides are N-terminal arginine-rich sequences and intramolecular disulfide bridges which introduce conformational constraint. PMID- 1446672 TI - Study of polynucleotide conformation by resolution-enhanced ultraviolet spectroscopy poly(rC) and poly(dC). AB - Self-deconvolution and the fourth derivative of ultraviolet absorption spectra have been used to study stacked single-stranded and double-helix structures of different cytosine-containing polynucleotides for the first time. These compounds were studied under different solution conditions (pH and organic solvents) and at low temperatures. The red shift of the lower band (B2u band plus possibly some n- >pi* transition) of the absorption spectra in the cytosine-containing polynucleotides and the appearance of new peaks in the deconvoluted and derivative spectra in the 280-310 nm region are attributed mainly to cytosine cytosine stacking interactions. In particular, the fourth-derivative peaks at wavelengths higher than 290 nm can be associated to coupling of electronic transitions of cytosine bases. The nature of the electronic transitions producing the absorption bands which are resolved in the aforementioned fourth-derivative peaks is discussed. It is concluded that the resolution-enhancement techniques used in this work, i.e. self-deconvolution and fourth derivative, complement each other and are useful methods to study structural changes of single-stranded and double-stranded polynucleotides allowing, at the same time, more information to be obtained about specific stacking interactions than classical absorption spectrophotometry. PMID- 1446673 TI - Alpha-crystallin exists in a non-spherical form. A study on the rotational properties of native and reconstituted alpha-crystallin. AB - Native alpha-crystallin, obtained from the cortex of calf lenses with FPLC (Pharmacia) was characterized by means of transient-electric-birefringence measurements and ultraviolet linear-dichroism spectroscopy. These techniques were also performed on 6-M-urea-dissociated and reconstituted alpha-crystallin. Transient-electric-birefringence measurements offer the possibility to characterize the often observed, but usually neglected, non-spherical occurrences of alpha-crystallin in more detail. Although not distinguishable with size exclusion chromatography, we could identify at least two different classes of both native and reconstituted alpha-crystallin, from which at least one consists of non-spherical molecules. The results are compared with those obtained with electron microscopy using different staining methods. From the three independent techniques used we find evidence that a fraction of the alpha-crystallin exists in a more extended quaternary structure. The results are difficult to explain with a concentric three-layer model for alpha-crystallin as proposed by Tardieu et al. [Tardieu, A., Laporte, D., Licinio, P., Krop, B. & Delaye, M. (1986) J. Mol. Biol. 192, 711-724]. PMID- 1446674 TI - Calorimetric measurements of thermal denaturation of stefins A and B. Comparison to predicted thermodynamics of stefin-B unfolding. AB - Thermal denaturation of two homologous proteins, low-M(r) cysteine-proteinase inhibitors stefins A and B, has been investigated by microcalorimetry. Calorimetric enthalpies, as well as the temperatures at maximum heat capacity, were determined as a function of pH for each protein. Transitions were found reversible at all pH values examined (5.0, 6.5, 8.1) for the thermally more stable stefin A, in contrast to stefin B. Stefin B shows a sharp irreversible transition around 65 degrees C at pH 6.5 and 8.1, probably due to unfolding of a dimeric state followed by oligomerisation. At pH 5.0, both proteins exhibit a reversible transition with temperatures of half-denaturation at 50.2 degrees C and 90.8 degrees C for stefins B and A, respectively. The calorimetric enthalpies, which equal the van't Hoff enthalpies to within 10%, are 293 kJ/mol and 490 kJ/mol for stefins B and A, respectively. Using the predictive method of Ooi and Oobatake (1991) [Proc. Natl Acad. Sci. USA 88, 2859] the thermodynamic functions of unfolding were calculated for stefin B, whose three-dimensional structure has been determined. The calculated enthalpy, heat-capacity change on unfolding and the temperature of half denaturation compare well to the microcalorimetric data. PMID- 1446675 TI - Inhibition of chloroplast ATPase by the K+ channel blocker alpha-dendrotoxin. AB - Possible structural and functional similarities between the channel part, CF0, of chloroplast ATPase (CF0CF1) and ion channels permeable to monovalent cations were investigated using high-affinity toxins mainly targeted against voltage-sensitive K+ channels. In particular, the effect of the K(+)-channel blocker alpha dendrotoxin and the crude scorpion venom of Leiurus quinquestriatus hebraeus (LQ venom) on ATP synthesis in thylakoid membranes and in CF0CF1-containing liposomes was characterised. Alpha-dendrotoxin (K(i) approximately 5.05 microM) and the LQ venom (K(i) approximately 1.55 micrograms/ml) specifically inhibited ATP synthesis in thylakoid membranes and in CF0CF1-containing liposomes. Our results show that alpha-dendrotoxin and peptides of the LQ venom with an apparent molecular mass of about 4.0 kDa, probably isoforms of charybdotoxin, specifically bind to CF0CF1. This binding was reversible and induced a high leak conductance for H+ through CF0. The Ca(2+)-dependent ATPase activity of the isolated soluble part of CF0CF1 (CF1) was completely inhibited by 1 microM alpha-dendrotoxin, while the crude LQ venom, at concentrations up to 10 micrograms/ml, had no affect on ATPase activity. The concentration dependence of the inhibition by alpha dendrotoxin indicates that approximately 2 mol alpha-dendrotoxin bind/mol CF0CF1 and 1 mol alpha-dendrotoxin/mol CF1. Known inhibitors of H(+)-flow-through CF0 acted in the presence of alpha-dendrotoxin synergistically. Dicyclohexylcarbodiimide and venturicidin, in contrast to their known effect of blocking H(+)-flow-through CF0, increased the leak conductance through CF0 in the presence of alpha-dendrotoxin drastically. This uncoupling effect indicates that their normal mode of blocking is a secondary effect. Binding of the inhibitors to their respective sites apparently does not affect the proton pathway in CF0, but induces a conformation which closes the channel part for H+. Protein sequence comparison between the known binding site of charybdotoxin in the shaker K+ channel from Drosophila [MacKinnon, R. & Heginbotham, L. (1990) Neuron 5, 767 771] and the choroplast ATPase showed that subunit III reveals a significant similarity (64%) in parts of its sequence (Gln28-Leu53) to the helix 5 and helix 6 (S5-S6) linker region (Ala413-Cys462; the charybdotoxin-binding site) of the shaker K+ channel. According to secondary-structure predictions, the homologous sequences in subunit III and the shaker K+ channel represent putative hydrophilic loops connecting two transmembrane alpha-helices. Apparently the shaker K+ channel and subunit III share significant topological features in these hydrophilic loops which may be part of the respective channel entrance. PMID- 1446676 TI - Kinetics of ATP synthesis catalyzed by the H(+)-ATPase from chloroplasts (CF0F1) reconstituted into liposomes and coreconstituted with bacteriorhodopsin. AB - The H(+)-ATPase from chloroplasts (CF0F1) was isolated, purified and reconstituted into liposomes from phosphatidylcholine/phosphatidic acid. A transmembrane pH difference, delta pH, and a transmembrane electric potential difference, delta psi, were generated by an acid/base transition. The rate of ATP synthesis was measured at constant delta pH and constant delta psi as a function of temperature between 5 degrees C and 45 degrees C. The activation energy was 55 kJ mol-1. CF0F1 was coreconstituted with bacteriorhodopsin at a molar ratio of approximately 1:170 in the same type of liposomes. Illumination of the proteoliposomes leads to proton transport into the vesicles generating a constant delta pH = 1.8. The dependence of the rate of ATP synthesis on ADP concentration was measured with CF0F1 in the oxidized state, E(ox), and in the reduced state, E(red). The results can be described by Michaelis-Menten kinetics with the following parameters: Vmax = 0.5 s-1, Km = 8 microM for E(ox) and Vmax = 2.0 s-1, Km = 8 microM for E(red). PMID- 1446677 TI - Contribution of de-novo and salvage synthesis to the uracil nucleotide pool in mouse tissues and tumors in vivo. AB - The relative contribution of de-novo and salvage synthesis to tissue pyrimidine nucleotide pools is an important parameter in the rational design of anti pyrimidine therapies, but has not been measured in vivo. We have measured the contribution of de-novo synthesis to the total acid-soluble uracil nucleotide pool in mouse tissues by analysis of the incorporation of label after intra peritoneal infusion of L-[15N]alanine. The contribution of salvage synthesis was measured by the incorporation of radiolabel after intravenous infusion of [14C]uridine. The results show that de-novo synthesis makes the larger contribution to the intestine uracil nucleotide pool, salvage synthesis makes the larger contribution to the kidney pool, and de-novo and salvage synthesis make roughly equal contributions to the liver pool. In tumors studied (L1210, P388, B16, Nettesheim), the contribution of de-novo synthesis was at least five times the contribution of salvage synthesis. The measurements were repeated 24 hours after a 400-mg/kg dose of N-phosphonacetyl-L-aspartic acid. De-novo synthesis was substantially inhibited in all tissues and tumors after this treatment, although significant residual activity was observed in the intestine and L1210 cells. Nettesheim carcinoma was the only tumor or tissue to show a significant increase in salvage synthesis after N-phosphonacetyl-L-aspartic acid treatment. PMID- 1446678 TI - Effect of 2-mercaptoethanol on glutathione levels, cystine uptake and insulin secretion in insulin-secreting cells. AB - The role of glutathione (GSH) in the differentiated state of insulin-secreting cells was studied using 2-mercaptoethanol as a means of varying intracellular GSH levels. 2-Mercaptoethanol (50 microM) caused a marked increase of GSH in two rat insulinoma cell lines, RINm5F and INS-1, the latter being dependent on the presence of 2-mercaptoethanol for survival in tissue culture. The effect of 2 mercaptoethanol on GSH was shared by other thiol compounds. Since in other cell types 2-mercaptoethanol is thought to act on cystine transport, thereby increasing the supply of cysteine for GSH synthesis, we have studied [35S]cystine uptake in INS-1 cells. At equimolar concentrations to cystine, 2-mercaptoethanol caused stimulation of [35S]cystine-uptake. The effect persisted in the absence of extracellular Na+, probably suggesting the involvement of the Xc- carrier system. INS-1 cells with a high GSH level, cultured 48 h with 2-mercaptoethanol, displayed a lower cystine uptake than control cells with a low GSH content. The effect of variations of the GSH levels on short-term insulin release was studied. No alteration of glyceraldehyde-induced or KCl-induced insulin release in RINm5F cells was detected. In contrast, both in islets and in INS-1 cells, a high GSH level was associated with a slightly lower insulin release. In INS-1 cells the effect was more marked at low glucose concentrations, resulting in an improved stimulation of insulin secretion. On the other hand, in islets, a decrease in the incremental insulin release evoked by glucose was seen. As in other cell types, oxidized glutathione (GSSG) was less than 5% of total GSH, and in INS-1 cells no change in the GSH/GSSG ratio was detected during glucose-induced or 3-isobutyl-1 methylxanthine-induced insulin release. In conclusion, 2-mercaptoethanol dependent INS-1 cells, as well as RINm5F cells and islets of Langerhans, display a low capacity in maintaining intracellular levels of GSH in tissue culture without extracellular thiol supplementation; 2-mercaptoethanol possibly acts by promoting cyst(e)ine transport; changes in GSH levels caused a moderate effect on the differentiated function of insulin-secreting cells. PMID- 1446679 TI - Characterization of a nitric-oxide-catalysed ADP-ribosylation of glyceraldehyde-3 phosphate dehydrogenase. AB - Auto-ADP-ribosylation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GraPDH) has recently been demonstrated to be dramatically stimulated in the presence of nitric oxide. In order to obtain insight into the sequence of events leading to ADP-ribosylation of GraPDH, we studied the target amino acid, the nucleotide cofactor requirement, pH dependency and the stoichiometry of the reaction. Basal as well as stimulated ADP-ribose transfer is inhibited by the SH-group alkylating reagent, N-ethylmaleimide. Furthermore, the radiolabel of auto-[32P]ADP-ribosylated GraPDH is removed by treatment with HgCl2, suggesting an ADP-ribose-cysteine bond. Several indirect and direct mechanistic considerations point to NAD+ as the only cofactor for the ADP ribosylation reaction, excluding the possibility of a reaction sequence involving a NAD-glycohydrolase(s) followed by nonenzymatic ADP-ribose transfer to GraPDH. Optimal ADP-ribosylations were carried out at alkaline pH values using 10 microM free NAD+ as the sole nucleotide cofactor. Bovine serum albumin with an S nitrosylated SH group can serve as a model of ADP-ribose transfer from NAD+ and suggests that the nitric-oxide-modified SH group (S-nitrosylated SH group) is a prerequisite for the reaction. PMID- 1446680 TI - The use of alternative substrates in the characterization of actin-methylating and carnosine-methylating enzymes. AB - Actin isolated from nearly every eukaryotic species contains approximately 1 mol 3-methylhistidine/mol protein. His73 in actin has been shown, by protein sequencing, to be the site of methylation. The methylation occurs enzymically and post-translationally. A rabbit skeletal muscle myofibrillary fraction has previously been shown to contain a histidine methyltransferase activity that is actin specific. Detailed study of this enzyme has been hampered by lack of a suitable substrate assay. Naturally occurring actins are poor substrates for the enzyme, presumably due to prexistent methylation at His73. In this study, two potential alternative substrates have been investigated. These are a chicken beta actin expressed in Escherichia coli as a fusion protein with 80 amino acids of an influenza protein, NS1, and a synthetic peptide, Tyr-Pro-Ile-Glu-His-Gly-Ile-Ile Thr, corresponding to residues 69-77 of actin. Both substrates were covalently methylated at histidine residues in the presence of S-adenosylmethionine and partially purified enzyme fractions from rabbit muscle. In methylation experiments employing the fusion actin in the form of inclusion bodies, 3 methylhistidine is the major product, as is the case when soluble muscle or non muscle actin is used. However, for the synthetic peptide, the methylated product primarily contained 1-methylhistidine and only a small amount of the isomeric 3 methylhistidine. Further investigations revealed that the peptide was recognized by carnosine N-methyltransferase, another histidine methyltransferase found in muscle tissue. Carnosine N-methyltransferase appears to copurify with the actin methylating enzyme in preliminary fractionation experiments. Separation of the two methyltransferase activities is described. PMID- 1446681 TI - The human rhabdomyosarcoma cell line A204 lays down a highly insoluble matrix composed mainly of alpha 1 type-XI and alpha 2 type-V collagen chains. AB - The biosynthesis of collagen by the A204 cell line was examined using polyclonal antibodies raised against collagen type V and type XI. The study of the pepsin digested collagen showed that it is composed mainly of alpha 1(XI) and alpha 2(V) collagen chains in an apparent 2:1 ratio, suggesting the formation of heterotypic molecules [alpha 1(XI)]2 alpha 2(V). The existence of this chain stoichiometry was further demonstrated by immunoprecipitation of the molecule with an antibody recognizing alpha 2(V) but not alpha 1(XI) collagen chains. Electron microscopy analyses of 24-h cultures showed that this matrix is composed of thin fibrils, that can be decorated with immunogold-labelled anti-(type-V collagen) IgG, but not with anti-(type-XI collagen) IgG. The collagen matrix laid down by A204 cells is highly insoluble. In the presence of beta-aminopropionitrile, an inhibitor of lysyl oxidase, only a small proportion of intact collagen could be extracted without proteolytic treatment. Immunoblotting of intact medium collagen from cultures performed in the presence of beta-aminopropionitrile showed four distinct bands with each antibody. The migration of the bands, stained with anti (type-V collagen) IgG, had apparent molecular masses of 127, 149, 161 and 198 kDa (compared to globular standards) while the bands stained with anti-(type-XI collagen) IgG had apparent masses of 145, 182, 207 and 225 kDa. These data indicate that type-V and type-XI collagen chains can assemble in heterotypic isoforms. In this system, the synthesized isoforms are able to aggregate into a highly cohesive matrix and they undergo a proteolytic processing closely similar to that of other fibrillar collagens. PMID- 1446682 TI - The Soret magnetic circular dichroism of ferric high-spin myoglobins. A probe for the distal histidine residue. AB - To find a simple criterion for the presence of the distal (E7) histidine residue in myoglobins and hemoglobins, the Soret magnetic-circular-dichroic spectra were examined for ferric metmyoglobins from various species. A distinct and symmetric dispersion-type curve was obtained for myoglobins containing the distal histidine, whereas a relatively weak and unsymmetric pattern was observed for myoglobins lacking this residue, such as those from three kinds of gastropodic sea molluscs, a shark and the African elephant. The magnetic-circular-dichroic spectra obtained would thus be a direct reflection of the presence or absence of a water molecule at the sixth coordinate position of the heme iron(III), this axial water ligand being stabilized by hydrogen-bond formation to the distal histidine residue. On the basis of these Soret magnetic-circular-dichroic signals, we also examined the structure of a protozoan myoglobin (or a monomeric hemoglobin) from Paramecium caudatum of particular interest for the evolution of these proteins from protozoa to higher animals. PMID- 1446683 TI - Purification of assembly-competent tubulin from Saccharomyces cerevisiae. AB - We have developed a straightforward, two-step procedure to isolate highly purified yeast tubulin that reproducibly assembles into microtubules. The starting extracts are obtained from cells genetically engineered to overproduce both the alpha and beta subunits of tubulin, under control of the galactose promoter, to approximately 10-times wild-type levels. The first step of purification is carried out with the high-speed supernatant of lysed cells loaded onto a DEAE-Sephadex column; after this step the tubulin preparation is approximately 30% pure. In the second step, the tubulin fractions are loaded onto an immunoaffinity column prepared by coupling the anti-(alpha-tubulin) monoclonal antibody YL 1/2 to Sepharose-4B. Following elution with 0.8 M KCl, the tubulin present in the peak is 90% pure. Upon addition of porcine brain microtubule associated proteins or DEAE-dextran, this tubulin preparation is functionally active for assembly into microtubules, as visualized by electron microscopy on negatively stained samples. Virtually identical microtubule structures are produced in parallel experiments on the assembly of yeast or porcine brain tubulin, with differences observed only at acidic pH values. Overall, this relatively simple procedure provides a useful tool for the production of functional tubulin suitable both for structural studies and for investigations of the assembly process. PMID- 1446684 TI - Nuclear substrates of protein kinase C. AB - Starting from the finding that, for neuronal cells, the nuclear-membrane associated protein kinase C (PKC) is the so-called 'membrane inserted', constitutively active form, we attempted to identify substrates of this nuclear PKC. For this purpose, nuclear membranes and other subcellular fractions were prepared from bovine brain, and in-vitro phosphorylation was performed. Several nuclear membrane proteins were found, the phosphorylation of which was inhibited by specific PKC inhibitors and effectively catalyzed by added PKC. Combining the methods of two-dimensional gel electrophoresis, in-situ digestion, reverse-phase HPLC and microsequencing, two of these nuclear PKC substrates were identified; the known PKC substrate Lamin B2, which serves as a control of the approach and the nucleolar protein B23. Our data suggest, that, for B23, Ser225 is a site of phosphorylation by PKC. PMID- 1446685 TI - The effect of metal binding on the structure of annexin V and implications for membrane binding. AB - The structure of annexin V, crystallised in the presence of two calcium or barium ions for each protein molecule, was solved by molecular replacement to 0.24 nm resolution. The two metal ions are found in domains I and IV, i.e. on the same side of the channel that lies in the centre of the molecule. The structures of the barium and calcium form are extremely close, the only differences localised in the metal-binding sites that lie on the surface of the molecule. The occupancies of the metal ions, however, are lower for barium than for calcium, expressing the lower affinity of the protein for the former. The packing of the annexin molecules in the crystal asymmetric unit may represent a model for the calcium driven association of membrane-bound annexins that leads to membrane fusion. PMID- 1446686 TI - Purification and characterization of rat brain cytosolic 3,5,3'-triiodo-L thyronine-binding protein. Evidence for binding activity dependent on NADPH, NADP and thioredoxin. AB - A rat brain cytosolic 3,5,3'-triiodo-L-thyronine-(T3)-binding protein (CTBP) was purified using, successively, carboxymethyl-Sephadex, DEAE-Spherodex, T3 Sepharose-4B affinity chromatography and Sephacryl S-200. The molecular mass determined by SDS/PAGE wa 58 kDa. The binding characteristics determined by Scatchard analysis revealed a single class of binding sites with a Ka of 1.56 nM 1 and a maximal binding capacity of 7500 nmol T3/g protein. The relative binding affinities of iodothyronine analogues were D-T3 > L-T3 > L-T4 > 3,3'-5 triiodothyroacetic acid > reverse T3. The optimum pH for binding was 7.5. Purified brain CTBP was reversibly inactivated by charcoal. NADPH, NADP and thioredoxin restored binding activity to a level higher than that of the control; this effect was concentration dependent. Maximal activation was observed at 25 nM NADPH. NADP was effective only in the presence of 1 mM dithiothreitol; maximal activity was obtained at 10 nM NADP. At concentrations higher than 50 nM NADP, the binding gradually decreased. Thioredoxin in the presence of 1 mM dithiothreitol activated CTBP; maximal binding was obtained with 4 microM thioredoxin. In the presence of NADPH, NADP or thioredoxin the maximal binding capacity increased 2-4 times and the Ka was 2.6 nM-1. These results show that the activity of purified cytosolic brain T3-binding protein may be modulated by NADPH, NADP or thioredoxin. PMID- 1446687 TI - Coordination and internal exchange of two DNA molecules in a RecA filament in the presence of hydrolysing ATP. Information on ATP-RecA-DNA structure from linear dichroism spectroscopy. AB - Solution structure of complexes between DNA and recombinase RecA from Escherchia coli, in the presence of the physiological cofactor ATP, is probed by flow linear dichroism (LD) spectroscopy. A problem of ADP accumulation which promotes dissociation of DNA-RecA is circumvented by using an ATP-regenerating system. The LD features indicate that the local structure of the complex is very similar to that found in the presence of the non-hydrolysable analog of ATP, adenosine-5'-O [gamma-thio]triphosphate (ATP[gamma S]); the DNA bases are oriented with their planes preferentially perpendicular to the long axis of the filament, while the indole chromophores of the two tryptophan residues of RecA are rather parallel to this reference direction. A much smaller overall amplitude of the LD spectrum, compared to ATP[gamma S], is interpreted as a result of fast dissociation of RecA due to hydrolysis of ATP, producing transiently naked DNA regions which act like flexible joints, diminishing the macroscopic orientation of the RecA filaments. However, the ATP hydrolysis is not found to prevent simultaneous accommodation of two non-complementary DNA molecules in the RecA complex, as judged from the LD behaviour upon successive addition of two different polynucleotides or modified DNA strands. A notable difference from corresponding complexes formed with ATP[gamma S] is that, in the presence of ATP hydrolysis, the order in which the two DNA molecules have been added is insignificant as judged from virtually identical resulting structures; this observation indicates that exchange of DNA occurs between the two DNA accommodation sites within the RecA filament. PMID- 1446688 TI - Improvement in the heterogeneous N-termini and the defective N-glycosylation of human interleukin-6 by genetic engineering. AB - Recombinant human interleukin-6 (IL-6), expressed in Chinese hamster ovary cells, has heterogeneous N-termini of Ala1 and Val3, as does naturally occurring IL-6. This heterogeneity is thought to be caused by difficulty in cleavage of the signal sequence. To obtain homogeneous IL-6, Pro at -1 was exchanged for Ala by site-directed mutagenesis. Alternatively, the signal sequence was replaced with that of human granulocyte-colony-stimulating factor. In both cases, the IL-6 designed to start with Ala1 was still heterogeneous, while the IL-6 designed to start with Val3 showed a homogeneous N-terminus. It is suggested that the heterogeneity of the N-terminus is caused not only by the signal sequence, but also by the succeeding sequences of the mature protein. Only a portion of recombinant human IL-6 is N-glycosylated. Asn46, being exchanged for Gln by site directed mutagenesis, was confirmed to be partially N-glycosylated. The defective N-glycosylation was assumed to be caused by interference or tension from a disulfide bond near the N-glycosylation site. To verify this hypothesis, the Cys45 and Cys51 forming the disulfide bond were exchanged for Ser. The N glycosylated species became predominant upon this substitution, suggesting that formation of the disulfide bond is a cause of the defective N-glycosylation. PMID- 1446689 TI - Aminopeptidase P from human leukocytes. AB - Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure. Buffy coats were the starting material. A M(r) of 140,000 was obtained by size-exclusion HPLC for the native enzyme. As shown by SDS/PAGE under reducing and denaturing conditions, the enzyme consisted of likely identical subunits with M(r) of 71,000. Purified aminopeptidase P cleaved off, specifically and efficiently, the N-terminal residues from peptides with N-terminal Xaa-Pro sequences. The penultimate proline was not replaceable by hydroxyproline, alanine and glycine in di-, tri- and tetrapeptides. Polyproline was not hydrolyzed. Dipeptides were cleaved (Arg-Pro, Phe-Pro > Trp-Pro > Pro Pro) although slower than longer peptides. Cleavage was observed of several biologically active peptides; C-terminal fragment (residues 201-206) of C reactive protein, oxytocin fragment Tyr-Pro-Leu-Gly, morphiceptin, peptide Gly Pro-Arg-Pro (inhibitor of fibrin polymerization) and kentsin. In addition, cleavage of a protein, interleukin-6, was also demonstrated. Aminopeptidase P was maximally activated by Mn2+, and to a lesser extent by Co2+. The activity was optimal at pH 8. Ni2+, Zn2+ and especially Cd2+ caused marked inhibition. EDTA, 1,10-phenantroline and dithiothreitol were also inhibitory. Carbobenzoxy phenylalanine, as well as several N-carbobenzoxy-proline-containing peptides, caused partial inhibition. The observed resistance of Gly-Pro, Pro-Gly, Pro-Phe and Pro-Ile to hydrolysis by the purified enzyme strongly indicates absence of known proline-specific dipeptidases in the aminopeptidase-P preparation. PMID- 1446690 TI - Factorial invariance issues in the study of adult personality: an example using Levenson's locus of control scale. AB - Confirmatory factor analysis was used to examine factorial invariance across young, middle-aged, and elderly age groups, using Levenson's multidimensional locus of control (LoC) scale, which measures beliefs in Internal Control (I), Control by Powerful Others (P), and Chinese (C). Data were obtained from 563 individuals ranging in age from 25 years to 75 years of age who resided in Southeastern Louisiana. Results indicated that Levenson's 3-factor conceptualization of control was not a valid representation of the samples' responses. A model that specified the elimination of 17 unreliable items and the formation of both an internal and an external control factor that was based on the seven remaining I and P items provided an adequate fit to the data for the three age groups, though when additional constraints were specified, factorial invariance was not demonstrated. The 7-item I and P factor model generated a pattern of relationships with other measures which was similar to the pattern found if all items of the I and P scales were used. PMID- 1446691 TI - An adult developmental study of the encoding of spatial location. AB - The present study was designed to test the hypothesis that there is a differential deficit in the ability to encode contextual information with increasing age. Young, middle-aged, and elderly adults were shown target words in various quadrants of a computer screen (contexts) and were told to either (a) remember the words and their locations, (b) remember the words, or (c) tell whether the words referred to something that was alive or not. Following presentation of the words, subjects were given a recognition test for the words and were asked to identify the quadrant in which each word had been presented. If older adults have a contextual encoding deficit, than an interaction between age and instruction condition would be expected in memory for quadrants. Older adults would be expected to perform better relative to younger adults when the locations were target information (intentionally learned) than when they were contextual (not intentionally learned). Since such an interaction was not obtained, the results provide no support for the hypothesis that the elderly have an encoding deficit that is specific to contextual information. PMID- 1446692 TI - Self-judged comprehension in adults: effects of age and skill. AB - We used an error detection paradigm to examine the effects of skill on young (M = 23.74) and old (M = 68.87) adults' self-judged comprehension of texts. Skill was defined as the ability to evaluate comprehension by detecting text problems. Multiple regression results indicated that problematic texts produced lower comprehension judgments for older readers, regardless of level of skill, than for younger readers. Only more skilled younger readers tended to lower their comprehension judgments for problematic text. Younger adults who were less skilled at evaluating their comprehension assessed their comprehension as superior to their more skilled peers. Less skilled older adults appear to know, better than less skilled younger adults, when they do not comprehend a text. Research is needed to examine older adults' perceived self-efficacy and use of regulation strategies to resolve comprehension failures. PMID- 1446693 TI - Age-related differences in adults' macrospatial cognitive processes. AB - Young and elderly adults' performance was compared on the Landmark Selection Task, designed to assess perceptual selection, and the Scrambled Route Task, designed to assess temporospatial integration. Age-related performance decrements were found on both tasks. Subjects' scores on psychometric tests hypothesized as involving some of the same processes as these experimental tasks yielded positive correlations to measures of task performance. Unexpectedly, self-estimates of wayfinding and distance estimation skills were negatively correlated to experimental task performance for elderly adults. Results were discussed in the context of declines in the effectiveness of selective attention, which is considered critical to perceptual selection, and in the proficiency of working memory, which is considered central to temporospatial integration. PMID- 1446694 TI - Variation in external context and adult age differences in action memory. AB - Adult age differences were determined for the memory and retention of the content of actions. Variation in the physical context from the time of performance of the actions to the time of testing for their memory had no effect for either young or elderly adult subjects on the recall or the recognition of the actions either shortly after acquisition or 24 hours later. Both young and elderly subjects showed significant forgetting of actions over a 24-hour retention interval as measured by recall. PMID- 1446695 TI - Continuously distributed random variables in factorial designs. AB - Age as a variable in lifespan research usually is sampled as several age blocks which, in turn, are combined with additional variables in a factorial design. Sampling a continuous variable in discrete blocks increases the difficulty in obtaining adequate sampling, reduces power, and prevents a fine grain analysis of age x treatment interactions. Age can be sampled as a continuously distributed variable, factorially combined with treatment groups, and analyzed as an analysis of variance by the use of regression analysis and comparison of multiple R2 coefficients. The advantages of such a sampling strategy include both practical sampling advantages as well as statistical advantages when compared with the usual sampling approach. PMID- 1446696 TI - Adult age differences in the storage of information in working memory. AB - The performance of 97 young and 91 old persons were compared to determine if a deficiency in working memory resources for processing, storage, or allocation could be detected. Persons simultaneously performed a storage and one of two processing tasks while instructed to allocate resources to processing, storage, or both tasks. The storage task involved remembering the names of one, three, or five persons. Processing tasks involved solving addition problems presented on flashcards or answering common knowledge questions. Results showed increased age differences on the storage task as demands for resources increased but no differences on processing tasks. Individuals seemed unable to allocate resources as instructed. A comparison of young-old and old-old groups showed the same results as those obtained comparing young and old groups and support the hypothesis of a deficiency of storage, but not processing, resources in working memory for old, especially old-old, adults. PMID- 1446697 TI - Age differences in sensitivity, response bias, and reaction time on a visual discrimination task. AB - Twelve young adults (age 21-25 years) and twelve older adults (age 57-65 years) performed a visual discrimination task (parallel lines) in which the following factors were manipulated: the difference in the length of the lines (3% and 9%), signal exposure duration (150, 750, and 2000 ms), and presentation modality (simultaneous and successive). The effect of repeating the task over three blocks was also controlled. Reaction time, sensitivity (d'), the decision criterion (beta), and the level of confidence the subjects had in their responses were measured and analyzed. The reaction time of the older subjects was longer than for younger ones. The difference remained constant across conditions. Signal detection analysis indicated that the ability to discriminate, as measured by d', was the same, on the whole, in the two age groups, but the sensitivity of the older was more affected by signal exposure duration than that of their younger counterparts. Contrary to what might have been expected, the older subjects used a more risky decision criterion than the younger subjects (preferring false alarms to omissions) and did not have significantly less confidence in their responses. Task repetition led to reduced reaction times and to a slightly higher level of confidence, but no age-related effects were found. The findings suggest that, in addition to a perceptual compensatory component, the longer reaction times of the older subjects include a decision-making component not necessary for their level of discrimination accuracy. The outcome of a lower criterion in the older group supports other findings according to which a more conservative decision strategy is not a general, systematic feature of the aged. PMID- 1446698 TI - Age cohort differences in the ability to perform closure on degraded figures. AB - Young (17-26) and old (60-80) men and women performed a perceptual closure task for degraded line drawings under three conditions of prior picture knowledge (exact, similar, no prior knowledge) and two conditions of perceptual noise (contour or detail drawings) resulting in six levels of task difficulty. Young and old subjects took equal advantage prior knowledge conditions, however, old subjects required a greater percentage of picture and more time to make closure under all conditions when compared to young subjects. To test the perceptual slowing hypothesis, old subject performance was regressed on that of young across three levels of task difficulty. The slope of these regression equations supported the notion of a perceptual slowing hypothesis to explain age cohort differences. PMID- 1446699 TI - Aging, narrative organization, presentation mode, and referent choice strategies. AB - We examined age differences in referent choice strategies when narrative organization and presentation mode taxed working memory. Readers could use the following cues to choose referents for an ambiguous pronoun: (a) thematic cue (main/minor character), (b) foreground cue (character in main/subordinate clause), and (c) recency of mention of character. Subjects read short narratives with a critical sentence that mentioned the main character in the main clause of the critical sentence (congruent condition) or in the subordinate clause of this sentence (incongruent condition). They chose the main or minor character as referent for a pronoun in the next (target) sentence. Experiment 1 examined how older and young readers use these cues with the Memory narrative presentation (target sentence presented on a separate page from the rest of the narrative). Young readers used similar strategies as those in Morrow (1985), where narrative presentation did not tax memory. Thus, the Memory presentation had little influence on their strategies. However, older readers were less consistent and tended to split in choosing the two characters. In Experiment 2, where narrative presentation did not tax working memory, older readers used similar strategies to the young readers in Experiment 1. Experiment 3 found that elders reading narratives with the Memory presentation recalled the nonpreferred character name after the narrative, suggesting that both characters were accessible from working memory. The study suggests that the Memory presentation mode in Experiment 1 interfered with elders' consistent use of narrative cues in choosing referents, especially when these cues conflict. PMID- 1446700 TI - Object recognition by component features: are there age differences. AB - This study extended aspects of Biederman's (1987) recognition-by-components (RBC) theory to the analysis of age differences in the recognition of incomplete visually-presented objects. RBC theory predicts that objects are recognizable or recoverable under conditions of fragmentation if a sufficient amount of essential structural information remains available. Objects are rendered nonrecoverable by the omission or obstruction of essential structural features at vertices and areas of concavity. Fifteen young adults and 15 older adults participated in a study of the effects of amount (25%, 45%, 65%) and type of fragmentation (recoverable, nonrecoverable) on object naming. Age-related declines in recognizing incomplete objects were associated with the amount of fragmentation, but type of fragmentation did not affect the performance of older adults. For the young adults, accuracy of performance was affected by both amount and type of fragmentation, consistent with Biederman's RBC theory. These results were interpreted as suggesting that age-related declines in perceptual closure performance have to do with non-structural factors such as the ability to inferentially augment degraded or missing visual information. PMID- 1446701 TI - In vivo priming of cytotoxic T lymphocyte responses in relation to in vitro up regulation of major histocompatibility complex class I molecules by short synthetic peptides. AB - Cytotoxic T lymphocytes (CTL) recognize target antigens as short peptides presented by major histocompatibility complex class I molecules (MHC-I). Externally added peptides can sensitize target cells by binding directly to MHC-I without any need for internal processing. Those which are similar in length to endogenously processed peptides are more potent in this respect than slightly longer peptides. Peptide MHC-I interactions can also be reflected as up regulation of MHC-I in vitro on certain cells. We have compared the capacity of Db, Kb- and Ld-binding peptides, which are slightly different in length, to up regulate MHC-I in vitro with their immunogenicity in vivo, in relation to generation of CTL responses. A clear correlation between these two different functions was found. We have also modified a 9-mer Db-binding peptide by adding cystein to the amino terminus and lysine to the amino- or carboxy terminus and studied the effects on MHC-I up-regulation and in vivo immunogenicity. Cystein and lysine contain reactive groups which are likely to influence the binding of modified peptides into the antigen-binding groove of Db. These small modifications of the optimal 9-mer peptide strongly influenced their functions but still there was a correlation between MHC-I up-regulation and CTL responses. Up-regulation of MHC-I in vitro may reflect a capacity of peptides to accumulate on the surface of particular antigen-presenting cells in vivo. PMID- 1446702 TI - Immunomodulation of streptococcal cell wall-induced arthritis. Identification of inflammatory cells and regulatory T cell subsets by mercuric chloride and in vivo CD8 depletion. AB - Streptococcal cell wall (SCW)-induced arthritis is a chronic, erosive polyarthritis which can be induced in susceptible Lewis rats by one intraperitoneal injection of a sterile, aqueous suspension of SCW. The chronic phase of the disease is dependent on T cells. Mercuric chloride is an immunomodulating agent, causing autoimmunity in BN rats, but an OX8+ cell mediated immunosuppression in Lewis rats. Therefore, we investigated the effect of mercuric chloride, whether or not combined with in vivo OX8 depletion, on SCW induced arthritis in Lewis rats. We show that (a) depletion of OX8+ cells leads to a more chronic arthritis with a more rapid onset, (b) treatment with mercuric chloride induces a rapidly developing disease which is not chronic, and (c) treatment with mercuric chloride and OX8+ cell depletion induces an arthritis with a very rapid onset and enhanced chronicity. Together with histological data this suggests an important role for OX8+ T cells in controlling both the acute and chronic phase of the disease. In addition, mercuric chloride seems to induce an early activation of T cells resulting in an enhanced onset of disease, which is controlled later by enhanced activation of OX8+ cells. PMID- 1446703 TI - Interferon-alpha prevents endotoxin-induced mortality in mice. AB - Endotoxins, the lipopolysaccharide (LPS) moieties on the bacterial cell wall, cause many of the pathological features of Gram-negative septicemia. Tumor necrosis factor (TNF), primarily a product of monocyte/macrophages, has been shown to mediate many of the pathophysiological effects of endotoxin. Kupffer cells, the largest macrophage population in the body, release TNF when stimulated by LPS in vitro. A recombinant human hybrid interferon-alpha A/D (rIFN-alpha) markedly inhibited this LPS-elicited TNF production by Kupffer cells. The effects of rIFN-alpha were further tested in C57BL/6 mice receiving a lethal dose (400 micrograms/mouse) of LPS. All LPS-treated mice died within 2 days. Pretreatment with rIFN-alpha 1 h before LPS challenge improved the survival at 3 days to 22% (5/23, p < 0.04). In contrast, rIFN-alpha was more effective when administered 20 min after LPS injection, increasing the survival rate to 81% (13/16, p < 0.0001). TNF mRNA expression in the liver and spleen 50 min after LPS challenge, and plasma TNF 1.5 h after LPS were also reduced by either pretreatment or post treatment with rIFN-alpha. Subsequently, experiments were carried out to test the efficacy of delayed rIFN-alpha treatment. A significant protective effect was still apparent when rIFN-alpha was administered 6, 10 and even 14 h (81%, 62% and 28% survival, respectively) after LPS challenge when serum TNF levels had already returned to near baseline. These experimental results suggest that rIFN-alpha might have a therapeutic potential for the prevention and treatment of the deleterious effects associated with endotoxemia besides mechanisms initially blocking TNF production. PMID- 1446704 TI - Functional role of alpha 2/beta 1 and alpha 4/beta 1 integrins in leukocyte intercellular adhesion induced through the common beta 1 subunit. AB - Whereas all of the integrins in the VLA protein subfamily are involved in cell extracellular matrix interactions, only VLA-4 (through the alpha 4 subunit) has been implicated in the triggering of intercellular adhesion. Here we describe that the VLA protein beta 1 subunit (CD29) is also involved in the induction of homotypic cell aggregation. We have obtained three novel anti-beta 1 monoclonal antibodies (mAb) with the ability to induce cell aggregation on different leukocyte cell types. These mAb recognize an antigenic site on the common beta 1 chain of VLA proteins which is topographically and/or functionally distinct from other epitopes previously defined by several prototype anti-beta 1 mAb. Induction of cell aggregation by anti-beta 1 mAb is epitope specific, isotype and Fc independent, and displays kinetics similar to alpha 4-mediated aggregation. This cell aggregation requires an intact cellular metabolism, the presence of divalent cations in the extracellular medium, and the integrity of the cytoskeleton. We also have found that the Na+/H+ antiporter may be essential for this process. For Ramos cells, which bear only the VLA alpha 4/beta 1 heterodimer, intercellular adhesion induced through the VLA-beta 1 chain could be selectively inhibited by other anti-beta 1 mAb as well as by anti-alpha 4 mAb. Interestingly, anti-beta 1 mAb which induced strong aggregation of VLA-alpha 2- or VLA-alpha 4-transfected K562 cells, had minimal effect on the alpha 2- alpha 4- alpha 5+ K562 cell line. Furthermore, the beta 1-mediated induction of cell aggregation on alpha 2-K562- and alpha 4-K562-transfected cells was blocked by preincubation with either anti alpha 2 or anti-alpha 4 mAb, respectively, as well as by other anti-beta 1 mAb. Interestingly, parental K562 cells were able to interact with both alpha 2- and alpha 4-transfected K562 cells, thus suggesting that counter-receptors for both integrins (VLA-2 and VLA-4) might exist on these cells. Together these results provide strong evidence supporting the involvement of alpha 2/beta 1 and alpha 4/beta 1 heterodimers in intercellular interactions and underline the pivotal role of the common beta 1 chain of VLA proteins in the integrin-mediated induction of cell aggregation. PMID- 1446705 TI - Binding of T cell receptor to major histocompatibility complex class II-peptide complexes at the single-cell level results in the induction of antigen unresponsiveness (anergy). AB - Using dispersion cultures performed in semi-solid medium we demonstrate here that the interaction of T cell antigen receptor molecules with Ia-peptide complexes on the same cell surface results in T cell activation, without the production of lymphokines. This recognition of antigen at the single-cell level, induced a state of anergy which was not due to a decrease of surface T cell antigen receptor/CD3 complexes. The induction of anergy by peptide could not be prevented by the addition of various co-stimulatory signals, including antibodies to CD28, or CD2, high doses of interleukin-2 or phorbol ester. PMID- 1446706 TI - Vaccination or tolerance to prevent diabetes. AB - Experiments with transgenic mice expressing the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promoter (RIP) have demonstrated that potentially self-reactive T cells that normally ignore self peptides may nevertheless be induced by self peptides or "cross-reactive" foreign (e.g. viral) peptides that arise in the host in an immunogenic form; once activated these potentially self-reactive T cells may cause autoaggressive diseases (e.g. diabetes). The possibility of vaccinating against such T cell mediated immunopathological diseases was evaluated in the RIP-GP transgenic mouse line Bln. Any attempt to vaccinate with the self antigen itself (e.g. recombinant vaccinia virus expressing LCMV-GP) failed to protect mice from disease. However, immunization with a recombinant vaccinia virus expressing LCMV-nucleoprotein (vacc-NP) as a non-GP LCMV vaccine was able to modulate the immune response and prevented autoaggressive disease in a MHC-dependent fashion. In contrast, tolerance induction neonatally or, more generally applicable, by lethal irradiation and reconstitution with neo-self antigen-expressing bone marrow cells always resulted in prevention of virally induced diabetes in this model situation. PMID- 1446707 TI - Immunoglobulin kappa light chain germ-line transcripts in human precursor B lymphocytes. AB - B lymphoblastoid cell lines (BLCL), established from bone marrow and peripheral blood mononuclear cells from two severe combined immunodeficiency (SCID) patients, manifested a complete absence of genomic rearrangements of the immunoglobulin (Ig) heavy (H) and light (L) chain loci. The BLCL contained germ line transcripts of the Ig kappa region locus of approximately 1.2 kilobase (kb). By cDNA cloning and sequence analysis the transcripts were shown to consist of a C kappa segment, a J kappa 1 gene segment, 160 base pairs (bp) of J kappa 1 5' intervening sequence, containing the heptamer/nonamer recombination recognition sequences and at the 5' end a 523-bp segment designated human kappa zero, The first 206 bp of this 5' segment were homologous to the reported murine kappa zero region. Genomic restriction mapping and DNA sequence analysis demonstrated that the human kappa zero segment is located approximately 4 kb upstream of J kappa 1. The kappa zero segment contains a putative promoter region with an OCT2 binding site, and has a splice donor site to accomplish splicing to an acceptor site 160 bp upstream of J kappa 1. Expression of the kappa zero gene segment was found in BLCL derived from normal fetal bone marrow, in which both Ig kappa loci were in the germ-line configuration. These findings indicate that the described transcripts are not only present in SCID, but also in normal developing pre-B lymphocytes. The expression of germ-line Ig kappa L chain transcripts may be associated with the locus becoming accessible to gene rearrangement. PMID- 1446708 TI - Modulation of oral tolerance to ovalbumin by cholera toxin and its B subunit. AB - Oral administration to mice of ovalbumin (OVA), if given together with cholera toxin (CT) or its B subunit (CTB) prevented the hyporesponsiveness to OVA subsequently injected parenterally. Oral immunization with CT plus OVA or OVA plus CTB in fact primed the immune system, inducing a stronger response to a subsequent parenteral injection of OVA with complete Freund's adjuvant than in mice prefed only with OVA or with saline. Oral CT plus OVA also induced good serum IgG1 and IgA anti-OVA responses, with slightly (not significant) decreased IgG2a and IgG2b responses. Our in vivo findings agree well with earlier in vitro data from others, including CT inhibition of the Th1 CD4+ T cell subset and with CT effect on B cells (induction of LPS-stimulated IgM+ B cells to undergo increased switch differentiation to IgG1- and IgA-secreting cells). PMID- 1446709 TI - Induction of primary anti-viral cytotoxic T cells by in vitro stimulation with short synthetic peptide and interleukin-7. AB - The present study investigated whether a short synthetic peptide NPP, with a modified sequence (147-158 R156-) derived from influenza A virus nucleoprotein with high affinity for Kd major histocompatibility complex class I molecules, could induce primary influenza virus-specific cytotoxic T (Tc) cells in vitro. Naive BALB/c (H-2d) splenocytes did not respond to the stimulation with only NPP with the generation of effector Tc cells specific for influenza A virus-infected target cells in vitro. However, they were able to do so if cultured with NPP in the presence of IL-7. IL-7 activity in this system differed significantly from IL 2 activity in the specificity of the effect. The use of exogenous IL-2, instead of IL-7, with NPP resulted in the induction of lytic cells that lysed both influenza virus-infected and uninfected syngeneic target cells. These results suggest that IL-7 is a potent regulatory cytokine in the antigen-specific activation of resting naive Tc cell precursors and may provide the necessary conditions for the induction of human primary Tc cells in vitro. PMID- 1446710 TI - Peritoneal exudate lymphocyte and mixed lymphocyte culture hybridomas are cytolytic in the absence of cytotoxic cell proteinases and perforin. AB - We have utilized the sensitive polymerase chain reaction (PCR) to determine whether cytotoxic T lymphocyte (CTL) hybridomas generated from peritoneal exudate lymphocytes (PEL) and mixed lymphocyte cultures (MLC) express transcripts for perforin and the cytotoxic cell proteinases CCP1 to CCP5. We could readily detect less than one transcript per cell using this methodology. Cytolytic activity could be induced to varying levels in four of the five hybridoma clones tested. With the exception of low level CCP2 expression in the MLC hybridoma MD45 following antigen stimulation, all of the hybridomas could be stimulated to function as potent cytolytic cells in the complete absence of perforin or CCP transcripts. PCR analysis utilizing actin primers indicated that all samples contained material which could be reverse transcribed and PCR-amplified. These results support the argument that populations of lymphocytes do exist that are capable of target cell lysis by an alternative mechanism not involving perforin and CCP. PMID- 1446711 TI - Cocaine and dopamine differentially protect [3H]mazindol binding sites from alkylation by N-ethylmaleimide. AB - The binding of cocaine, d-amphetamine and dopamine to the site on the dopamine transporter labeled by [3H]mazindol was investigated in rat striatal membranes. N Ethylmaleimide inhibited about 95% of the specific binding of 5 nM [3H]mazindol in a concentration-dependent manner. The effect of 10 mM N-ethylmaleimide was completely prevented by cocaine (EC50 of 3 microM), but neither 300 microM dopamine nor d-amphetamine afforded any significant protection. On the other hand, high concentrations of cocaine, d-amphetamine and dopamine provided similar protection against inhibition by 0.1 mM N-ethylmaleimide. Taken together these data support the hypothesis that a significant portion of the cocaine binding domain on the transporter is distinct from that of either dopamine or amphetamine. This distinction may be sufficient to allow properly designed drugs to prevent cocaine binding without inhibiting DA transport. PMID- 1446712 TI - Evidence for mutually exclusive binding of cocaine, BTCP, GBR 12935, and dopamine to the dopamine transporter. AB - The present study addressed the possibility that there are distinct but allosterically interacting populations of binding sites for dopamine/cocaine and BTCP/GBR (N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine/1-(2-diphenylmethox y) - ethyl]-4-(3-phenylpropyl)piperazine) (selective dopamine uptake blockers) on the dopamine transporter in the rat striatum. Dopamine uptake sites were labeled in vitro with the cocaine analog [3H]CFT (2 beta-carbomethoxy-3 beta-(4 fluorophenyl)-tropane), and the inhibition of binding by CFT or cocaine was measured. A graphic method was adopted for studying shifts in inhibitory potency resulting from the addition of a second compound. Under the conditions used, the co-presence of dopamine, GBR 12935, or BTCP decreased the inhibitory potency of CFT or cocaine to the extent predicted by a model in which all compounds bind to the same site or the binding of all compounds is mutually exclusive. No evidence for negative allosteric interactions between CFT and BTCP was found in experiments comparing inhibition of [3H]CFT binding by BTCP at a low and high concentration of [3H]CFT. PMID- 1446713 TI - The positive inotropic calcium sensitizer EMD 53998 antagonizes phosphate action on cross-bridges in cardiac skinned fibers. AB - The diazinone derivative EMD 53998 sensitizes skinned myocardial fibers to Ca2+ and enhances maximal calcium-activated force (pCa = 4.5) by approximately 100%; the EC50 is 10 microM in the absence and about 30 microM in the presence of added inorganic phosphate (10 mM). Although concentrations of added phosphate as low as 0.5 mM inhibit force, at high concentrations of EMD 53998 (> or = 50 microM), phosphate only inhibits at concentrations exceeding 20 mM. These data suggest that the effects of EMD 53998 and phosphate are mutually antagonistic. Importantly, both EMD 53998 and phosphate had similar effects on force generation in troponin I-depleted (Ca(2+)-independent) skinned fibers, thus demonstrating that these compounds are likely to affect cross-bridges directly and not via the Ca(2+)-regulatory system. PMID- 1446714 TI - High basal expression of zif268 in cortex is dependent on intact noradrenergic system. AB - The transcription factor Zif268 displays high basal levels of expression in cortex that appear to be dependent on physiological synaptic activity. We report that selective lesions of the noradrenergic system induced by DSP4 markedly suppress basal zif268 mRNA levels in cortex. Accordingly, the noradrenergic system which projects extensively to the cortex and is tonically active may play a key role in maintaining normal patterns of gene expression in target neurons. PMID- 1446715 TI - Antisense oligonucleotide eliminates in vivo expression of c-fos in mammalian brain. AB - Immediate-early genes such as c-fos and NGFI-A are rapidly and transiently expressed in the striatum following amphetamine administration in vivo. Here we show that direct infusion of an antisense oligodeoxynucleotide to c-fos into striatum will reduce amphetamine-induced production of Fos-like immunoreactivity without affecting NGFI-A expression. These results suggest that it is possible to use antisense technology to study the role of immediate-early genes in specific sites in the brain in vivo. PMID- 1446716 TI - Immunological and neurobiochemical alterations induced by repeated oral exposure of phenol in mice. AB - Phenol, a major metabolite of benzene, is a potentially immunotoxic and neurotoxic substance of environmental significance. Male CD-1 mice were continuously exposed to 0, 4.7, 19.5, and 95.2 mg phenol/l in drinking water for 4 weeks. Various immune functions were evaluated and levels of selected neurotransmitters and metabolites measured in discrete brain regions. The doses of phenol did not produce any overt clinical signs of toxicity; peripheral red blood cell counts and hematocrits decreased. A dose of 95.2 mg/l suppressed the stimulation of cultured splenic lymphocytes by lipopolysaccharide, pokeweed mitogen, and phytohemagglutinin and the response in mixed lymphocyte cultures. The two high doses suppressed antibody production response to the T cell dependent antigen (sheep erythrocytes), as determined by plaque-forming cells, and serum antibody levels. Mice treated with phenol had lower levels of neurotransmitters in several brain regions. In the hypothalamus, a major norepinephrine-containing compartment, the concentrations of norepinephrine significantly decreased by 29 and 40% in groups dosed with 19.5 and 95.2 mg/l, while dopamine concentrations decreased in the corpus striatum by 21, 26, and 35% at 4.7, 19.5 and 95.2 mg/l, respectively. Phenol also decreased 5 hydroxytryptamine in the hypothalamus, medulla oblongata, midbrain and corpus striatum. Levels of monoamine metabolites decreased in the hypothalamus (5 hydroxyindoleacetic acid), midbrain (vanillylmandelic acid), corpus striatum (vanillylmandelic acid and dihydroxyphenylacetic acid), cortex (vanillylmandelic acid), and cerebellum (dihydroxyphenylacetic acid). PMID- 1446717 TI - Effects of cholesterol and oxysterols on gap junctional communication between human smooth muscle cells. AB - Intercellular communication is considered to play an essential role in maintaining and controlling cell growth, cell differentiation and homeostasis. Cell-cell communication can be regulated by factors that influence gap junctional function. In this study it was demonstrated that cholesterol and oxidized cholesterol have the potential to modulate gap junctional communication between human smooth muscle cells in an opposite way. Cholesterol supplementation to human smooth muscle cells resulted in an increase of gap junctional communication up to 130% with regard to the control values. However, autooxidized cholesterol inhibited gap junctional communication more than 40%. Testing of several pure cholesterol oxidation derivates on gap junctional communication demonstrated that all of them were capable to inhibit intercellular communication in the order 25 hydroxycholesterol greater than cholestan-3 beta,5 alpha,6 beta-triol greater than 7-ketocholesterol greater than cholesterol 5,6 alpha-epoxide. The cell-cell communication-inhibiting potency of these oxysterols is in accordance with their atherogenic potency. This implies that cholesterol oxidation products, instead of pure cholesterol, can be promoting factors in the atherogenesis by influencing gap junctional communication between arterial smooth muscle cells, the target cells of atherosclerotic lesions. PMID- 1446718 TI - Eosinophil peroxidase and 125I- ion binding in guinea-pig trachea. AB - The present study further characterizes ascorbic acid-dependent 125I- ion binding in guinea-pig trachea. Binding of 125I- ion in the presence of ascorbic acid was detected at the epithelial/submucosal interface, apparently involving individual cells containing peroxidase enzyme. A similar binding pattern was observed when hydrogen peroxide was substituted for ascorbic acid. Binding could be inhibited by the addition of the H2O2 degrading enzyme catalase or the peroxidase inhibitor thiourea. Results demonstrated that this binding was dependent upon the addition of, or endogenous production of hydrogen peroxide and its metabolism via airway eosinophil peroxidase. The relevance of this anomalous iodine binding phenomenon to radioiodinated ligand binding studies is discussed. PMID- 1446719 TI - Pharmacological aspects of arthritis induced by a muramyl dipeptide analogue in rats. AB - Fourteen consecutive daily subcutaneous injections of 4 mg/kg of the muramyl dipeptide analogue MDP-Lys(L18) into rats caused arthritis characterized by swelling of the tarsal joint, increases in lymphocytes and monocytes in the peripheral blood, and elevated serum immunoglobulin G (IgG). The present study was performed to evaluate the effects of indomethacin, phenylbutazone, dexamethasone, D-penicillamine, aurothioglucose, cyclophosphamide and cyclosporin A on this arthritis. Administration of indomethacin, phenylbutazone or dexamethasone inhibited the development of the tarsal joint swelling, suggesting that prostaglandins may be involved in the pathogenesis of the arthritis. Cyclophosphamide reduced the arthritis, together with decreases in the lymphocyte count and the serum IgG level. Cyclosporin A worsened the arthritis in a dose dependent manner and increased the neutrophil count without raising the serum IgG level, but inhibited the induction of adjuvant arthritis in rats with Mycobacterium bacilli. MDP-Lys(L18) may therefore induce arthritis differing in mechanism from adjuvant arthritis. PMID- 1446720 TI - Inhalation of carbon monoxide does not accelerate arteriosclerosis in cockerels. AB - The effects of chronic exposure to moderate levels of carbon monoxide (CO) upon the augmentation of arteriosclerotic plaque development were investigated in a series of in vivo studies. Cockerels were exposed to carefully regulated CO levels in dynamic exposure chambers. The plaque volume percentage in the aortic walls of experimental and control animals was determined by point-counting. Chronic CO inhalation, at levels up to 200 ppm, did not stimulate arteriosclerotic plaque development (at 200 ppm CO, carboxyhemoglobin (COHb) levels 10 min after exposures ended were 11-12%). When administered concomitantly with cholesterol feeding, CO did not augment plaque development. When administered after either carcinogen-associated or diet-promoted plaque size increases had occurred, CO elicited no further plaque size increases. Thus, in this animal model, daily exposures to moderately high CO levels were without discernable effect upon arteriosclerotic plaque development, although high COHb levels were attained. PMID- 1446721 TI - The nitromethylene heterocycle 1-(pyridin-3-yl-methyl)-2-nitromethylene imidazolidine distinguishes mammalian from insect nicotinic receptor subtypes. AB - Effects of the insecticidal compound 1-(pyridin-3-yl-methyl)-2-nitromethylene imidazolidine (PMNI) on different subtypes of the nicotinic acetylcholine receptor were studied in voltage-clamped locust thoracic ganglion neurons, mouse BC3H1 muscle cells and mouse N1E-115 neuroblastoma cells. In locust neurons 10 microM PMNI induced agonistic effects and subsequent complete block of 1 mM acetylcholine-induced inward currents. The same concentration of PMNI produced no significant agonistic and antagonistic effects on the endplate type nicotinic receptor in BC3H1 cells. Neuronal type nicotinic receptor operated ion currents in N1E-115 cells were blocked by 10 microM PMNI to 50% of the control value, while agonistic effects were not observed. The differential action of PMNI designates this compound as a potential new tool to distinguish between subtypes of the nicotinic acetylcholine receptor. PMID- 1446722 TI - Genetically engineered V79 Chinese hamster cells for stable expression of human cytochrome P450IA2. AB - V79 Chinese hamster cells were genetically engineered for stable expression of human P450IA2. Full length cDNA, encoding human P450IA2, was inserted into an SV40 early promoter containing eukaryotic expression vector and cointroduced with the selection marker neomycin phosphotransferase (conferring resistance to the neomycin derivative G418) into V79 Chinese hamster cells. The recombinant expression vector was introduced into two different V79 sublines, one expressing an endogenous acetyltransferase (V79-NH), the other not (V79-MZ). The presence of human cytochrome CYP1A2 cDNA in the G418 resistant V79 cell clones was confirmed by Southern blotting. The transcription of the cDNA into mRNA was detected by Northern blotting and the translation into an authentic cytochrome P450IA2 protein was shown by Western blotting. The enzymatic activity in these cells was determined by the cytochrome P450IA2-dependent methoxy-, ethoxy-, benzoxy-, and pentoxyresorufin dealkylation activity. PMID- 1446723 TI - Mechanisms of thrombocytopenia in patients with lymphoproliferative diseases. AB - Different factors are involved in the development of thrombocytopenia in patients with lymphoproliferative disorders. Significant correlation was detected between the number of megakaryocytes in bone marrow and platelet count (r = 0.485, p = 0.002, n = 37) and significant difference between the number of megakaryocyte in patients with normal platelet count (> 200,000/microliters) and patients with marked thrombocytopenia (platelet count < 100,000/microliters). All patients in the latter group (n = 15) had a relatively low number of megakaryocytes. Low but significant reverse correlation was found between the level of platelet associated IgG (PA-IgG) and platelet count (r = -0.249, p = 0.024, n = 82) and significant difference between the mean levels of PA-IgG in the groups of patients with platelet count > 200,000/microliters and < 100,000/microliters. PA IgG were increased in 46% of patients in the total group and in 65% of patients with platelet count < 100,000/microliters. The correlation between platelet count and PA-IgG was about 2 times higher in splenectomized (r = -0.549, p = 0.005, n = 24) than nonsplenectomized patients. All splenectomized patients with platelet count < 100,000/microliters (n = 8) had a significant increase in PA-IgG. Serum antibodies were detected in only 7% of tested patients. This group was characterized by severe thrombocytopenia (in 6 of 10 patients--platelet count < 50,000/microliters) and a high incidence of haemorrhages (in 5 of 10 patients). Thus the depression of platelet production was suggested to be the basic cause of thrombocytopenia in lymphoproliferative disorders. Involvement of immune mechanisms was revealed in a large number of patients and correlated with a deeper and more complicated thrombocytopenia. PMID- 1446724 TI - Reduced erythropoietin response to anaemia in elderly patients with normocytic anaemia. AB - We studied the effect of age on the relationship between haemoglobin and serum erythropoietin (EPO) levels in anaemic patients. 568 patients over 70 years of age were compared with 137 patients under 70 and a reference group of 144 patients of all ages with proven iron deficiency. EPO was measured using a radioimmunoassay. We found that elderly patients with a normocytic anaemia (N = 375) had a statistically lower EPO response than younger patients with normocytic anaemia (N = 61) (p < 0.05) or patients of all ages with iron-deficiency anaemia (p < 0.05). There was no difference between the sexes. Elderly patients with microcytic or macrocytic anaemia had a normal EPO response as compared to the "gold standard" of iron deficiency. These findings suggest that a proportion of elderly patients with normocytic anaemia has an impaired EPO response. PMID- 1446725 TI - Expression of adhesion antigens of human bone marrow megakaryocytes, circulating megakaryocytes and blood platelets. AB - There is evidence that mature megakaryocytes migrate into sinusoids, enter the blood and fragment in the vascular bed. We wondered whether differences in expression of adhesion antigens could be associated with the egress of megakaryocytes from bone marrow into the peripheral blood or the fragmentation into platelets. Megakaryocytes from human marrow were purified by counterflow centrifugal elutriation followed by a glycoprotein Ib-dependent agglutination procedure. Megakaryocytes from central venous blood and pulmonary arteries were purified by counterflow centrifugal elutriation alone. Adhesion antigens were labelled in an immunohistochemical assay. Both bone marrow megakaryocytes and platelets from healthy volunteers stained > 75% positive for CD36, CD41, CD42, Cdw49b (alpha subunit VLA2), Cdw49e (alpha subunit VLA5), Cdw49f (alpha subunit VLA6) and CD62. Circulating megakaryocytes, although > 75% positive for CD41, had, unlike platelets and bone marrow megakaryocytes, a reduced and remarkable heterogeneous (5-100% positive) labelling with antibodies against Cdw49b, Cdw49e, Cdw49f. These results could be confirmed by comparing the bone marrow megakaryocytes, circulating megakaryocytes and platelets from 7 patients that were recovered and processed at the same time. Morphologically mature, circulating megakaryocytes have, unlike bone marrow megakaryocytes, a heterogeneous expression of adhesion antigens, especially of Cdw49b, Cdw49e, and Cdw49f. PMID- 1446726 TI - Electrokinetic behaviour and surface sialic acid status of blood platelets in essential thrombocythaemia (ET). AB - We have previously reported, for platelets from patients with idiopathic thrombocytopenic purpura, that there was in increased electrophoretic mobility that was related to their increased sialic acid content. Heterogeneity in the circulating platelet pool of patients with essential thrombocythaemia (platelet counts 600-1000 x 10(9)/l) has also been investigated by preparative continuous flow electrophoresis (CFE). The surface charge-dependent separation profiles of all the patients' platelets showed marked anodal shifts compared with the profiles of platelets from age- and sex-matched control subjects separated under identical conditions. The increase above normal in the net electronegativity of the patients' platelets could not be accounted for by differences in surface neuraminidase-labile or total platelet sialic acid content. PMID- 1446727 TI - Results in hairy-cell leukemia patients treated with alpha-interferon: predictive prognostic factors. AB - Fourty-four evaluable patients with hairy cell leukemia (HCL) were treated with human lymphoblastoid alpha-interferon (alpha-IFN), at a dose of 3 x 10(6) Units a day for 12-18 months while 18 of them continued to receive a three times per week schedule at the same dose as maintenance treatment. Eighteen percent of patients achieved complete response, 64% partial response, and 18% minor response with a median duration of 37.5, 22.9 and 3.5 months respectively. Twenty patients (45%), all partial or minor responders, subsequently had progression of the disease. The progression occurred more frequently in patients who presented at diagnosis with a hairy-cell index value > 0.50 than in those who presented with a hairy-cell index < 0.50: 14/26 (54%) versus 2/11 (18%) respectively. In addition, the progression rate was more evident in "non-maintained" than in "maintained" patients: 16/26 (61.5%) versus 4/18 (22%). Restarting alpha-IFN treatment in 16 of the 20 progressed patients proved effective only in 9 of them. From these findings it appears that a low hairy-cell index at diagnosis correlates favorably with a good hematological response. Furthermore, continuous therapy with alpha IFN seems very useful in reducing the progression of the disease, in particular in patients with a very high hairy-cell index at diagnosis. PMID- 1446728 TI - Treatment of myelodysplastic syndromes with human granulocytic-macrophage colony stimulating factor (GM-CSF) or GM-CSF combined with low-dose cytosine arabinoside. AB - In a phase II study, 21 patients with MDS (RAEB, RAEBt, CMML and RA and RAS with severe cytopenia) were randomized to be treated with 3 courses of GM-CSF (3 micrograms/kg/day s.c.) alone (11 patients) or in combination with AraC (20 mg/m2/d s.c.) (10 patients) for 14-d periods, interrupted by 14-d rest periods. Eight patients discontinued the treatment. In the GM-CSF group a marked increase in WBC and neutrophil counts during each course of treatment administration were seen in most patients. Platelet counts decreased in 14 of 24 courses of treatment in the GM-CSF plus AraC group but in none of the GM-CSF group. Although the changes in the circulating blood cells were transient and the counts tended to return to the pretreatment levels during the rest periods, some more durable effects were seen. In 3/6 patients of the GM-CSF group who completed the designed treatment, both WBC and neutrophils remained elevated above the pretreatment levels throughout the 3-month period of treatment, while in one of them thrombocytopenia improved considerably. In the GM-CSF plus AraC group, 4 out of the 7 patients who completed the treatment showed an improvement of neutropenia as well as anaemia. In these 4 patients the BM percentage of blasts was also decreased. In conclusion, the results of this study indicate that GM-CSF given intermittently improves leukopenia in some patients with MDS. In addition, the administration of GM-CSF seems to prevent granulocytopenia of concurrent AraC treatment and may be of benefit in the treatment of these diseases. PMID- 1446729 TI - Transfusion problems in patients with Glanzmann's thrombasthenia. PMID- 1446730 TI - Cyclical haemopoiesis in association with familial refractory anaemia: cycling of progenitors and serum growth factor concentrations. PMID- 1446731 TI - All-trans retinoic acid toxicity. PMID- 1446732 TI - Sequential administration of OKT3 (anti-CD3) and interleukin-2 in two patients with chemoresistant hematological disease. PMID- 1446733 TI - Polycythaemia and hyperparathyroidism: a fortuitous association? PMID- 1446734 TI - Sweet's syndrome associated with inversion of chromosome 3q in a patient with refractory anemia. PMID- 1446735 TI - Identification of nuclear factors which interact with the 5' flanking region of the EF-1 alpha O gene in Xenopus laevis. AB - The EF-1 alpha O gene of Xenopus laevis is a stage-specific gene, being transcribed in oogonia and oocytes, but not in postmeiotic germ cells and terminally differentiated cells. We found that two trans-acting factors from oocyte nuclear extract are able to interact with a DNA sequence in the 5' upstream region of the EF-1 alpha O gene. Methylation interference experiments suggested that the two factors recognised the same DNA element. Gel retardation assays indicated that part of the protein binding site could be confined to a 21 bp sequence, located between -51 and -72, relative to the cap site. Interestingly, this region shares great homology to a negative regulatory segment in the promoter of the TFIIIA gene, another developmentally regulated gene. PMID- 1446736 TI - Interferon-mediated intracellular signalling. Modulation of different phospholipase activities in Burkitt lymphoma cells. AB - The effect of interferon-alpha on Daudi lymphoma cells either sensitive or resistant to the action of this cytokine has been analysed in terms of phospholipase C (PLC) and D (PLD) activities. Results have shown a combined modulation of PIP2-specific phospholipase C and phospholipase D. In particular, a decreased activity of PIP2-specific PLC has been found, concomitant to a PLD mediated phosphatidylcholine hydrolysis, suggesting that the intracellular signalling activated by interferon in Daudi cells involves a phospholipase D/phosphohydrolase pathway. PMID- 1446737 TI - Xenopus laevis oocyte G alpha subunits mRNAs. Detection and quantitation during oogenesis and early embryogenesis by competitive reverse PCR. AB - The expression of mRNAs coding for different Xenopus laevis oocyte G alpha subunits was analyzed by the PCR technique. Using the nucleotide sequences of five previously cloned cDNAs for oocyte G alpha subunits [FEBS Lett. 244, 188 192, 1989; FEBS Lett. 268, 27-31, 1990] and the highly sensitive reverse PCR reaction we found that G alpha o, G alpha i-1, G alpha i-3 and G alpha s species are present in oocyte stage VI, G alpha o mRNA being the most abundant transcript. G alpha o mRNA was further quantitated through oogenesis, unfertilized eggs and early embryogenesis stages by a competitive PCR reaction using an 'in vitro' deleted G alpha o mRNA as the internal standard. Using this approach we found that Xenopus G alpha o mRNA levels were constant during oogenesis and unfertilized eggs at a concentration of 3.5 pg of mRNA/stage (5 x 10(5) molecules) and diminish gradually during early embryogenesis, reaching a level of 0.3 pg in the gastrula stage. These findings show that oocyte G alpha o, and perhaps the rest of the alpha subunits, are expressed as maternal mRNAs and could play an important role in signal transduction at the beginning of oocyte cell differentiation. PMID- 1446738 TI - Expression, characterization and purification of soluble G-protein beta gamma dimers composed of defined subunits in baculovirus-infected insect cells. AB - Recombinant beta 1 gamma 2 dimers of signal-transducing guanine nucleotide binding proteins (G-proteins) carrying a mutation known to block isoprenylation of the gamma 2 subunit were expressed as a soluble protein in baculovirus infected insect cells. The soluble beta gamma dimer was analyzed by sucrose density gradient centrifugation and purified to near homogeneity in the absence of detergents. The sedimentation velocity studies gave an S20,w value of 4.1 +/- 0.4 S. The two subunits segregated as a dimer upon sucrose density gradient centrifugation and purification by sequential ion exchange and hydroxylapatite chromatography. The results show that baculovirus-infected insect cells can be employed for high level production of pure G-protein beta gamma dimers suitable for functional and structural characterization. PMID- 1446739 TI - The primary structure of a PYY-related peptide from chicken intestine suggests an anomalous site of cleavage of the signal peptide in preproPYY. AB - Although the amino acid sequence of members of the pancreatic polypeptide (PP) family of regulatory peptides has been poorly conserved during vertebrate evolution, the overall length of the peptides (36 amino acid residues) has remained constant. Nucleotide sequence analysis of cloned cDNAs and/or genomic fragments has shown the PP-related sequence immediately follows the signal peptide in the prepropeptides. A peptide tyrosine-tyrosine (PYY)-related peptide with 37 residues has been isolated from the chicken intestine, and its primary structure was established as: Ala-Tyr-Pro-Pro-Lys-Pro-Glu-Ser-Pro-Gly10-Asp-Ala Ala-Ser-P ro-Glu-Glu-Ile-Ala-Gln20-Tyr-Phe-Ser-Ala-Leu-Arg-His-Tyr-Il e-Asn30-Leu Val-Thr-Arg-Gln-Arg-Tyr.CONH2. The presence of an additional alanine residue at the NH2-terminus of the peptide suggests that the site of cleavage of the signal peptide in chicken preproPYY is different from the site of cleavage in other PP family prepropeptides. PMID- 1446740 TI - Three-dimensional structure of apotransketolase. Flexible loops at the active site enable cofactor binding. AB - The structure determination of apotransketolase and the comparison of its three dimensional structure with that of the holoenzyme has revealed that no large conformational changes are associated with cofactor binding. Two loops at the active site are flexible in the apoenzyme which enables ThDP to reach its binding site. Binding of the cofactor induces defined conformations for these two loops at the active site. One of these loops is directly involving in binding of the cofactors, Ca2+ and ThDP. This loop acts like a flap which closes off the diphosphate binding site. After binding of the cofactor, residues of this loop form interactions to residues of loop 383-398 from the second subunit. These interactions stabilize the conformation of the two loops from a flexible to a 'closed' conformation. PMID- 1446741 TI - The length of the interdomain region of the L7/L12 protein is important for its function. AB - Several mutated L7/L12 proteins with changed interdomain regions were obtained. The results showed that the flexible region comprising the 39-52 amino acid residues is functionally important. Its length, but not its amino acid composition, is crucial for the function. PMID- 1446742 TI - A laser flash absorption spectroscopy study of Anabaena sp. PCC 7119 flavodoxin photoreduction by photosystem I particles from spinach. AB - Electron transfer from P700 in photosystem I (PSI) particles from spinach to Anabaena sp. PCC 7119 flavodoxin has been studied using laser flash absorption spectroscopy. A non-linear protein concentration dependence of the rate constants was obtained, suggesting a two-step mechanism involving complex formation (k = 3.6 x 10(7) M-1.s-1) followed by intracomplex electron transfer (k = 270 s-1). The observed rate constants had a biphasic dependence on the concentrations of NaCl or MgCl2, with maximum values in the 40-80 mM range for NaCl and 4-12 mM for MgCl2. To our knowledge, this is the first time that the kinetics of PSI dependent flavodoxin photoreduction have been determined. PMID- 1446743 TI - Mode of action of the Spiroplasma CpG methylase M.SssI. AB - The cytosine DNA methylase from the wall-less prokaryote, Spiroplasma strain MQ1 (M.SssI) methylates completely and exclusively CpG-containing sequences, thus showing sequence specificity which is similar to that of mammalian DNA methylases. M.SssI is shown here to methylate duplex DNA processively as judged by kinetic analysis of methylated intermediates. The cytosine DNA methylases, M.HpaII and M.HhaI, from other prokaryotic organisms, appear to methylate in a non-processive manner or with a very low degree of processivity. The Spiroplasma enzyme interacts with duplex DNA irrespective to the presence of CpG sequences in the substrate DNA. The enzyme proceeds along a CpG-containing DNA substrate molecule methylating one strand of DNA at a time. PMID- 1446744 TI - Interrelations of M-intermediates in bacteriorhodopsin photocycle. AB - The photocycles of the wild-type bacteriorhodopsin and the D96N mutant were investigated by the flash-photolysis technique. The M-intermediate formation (400 nm) and the L-intermediate decay (520 nm) were found to be well described by a sum of two exponents (time constants, tau 1 = 65 and tau 2 = 250 microseconds) for the wild-type bR and three exponents (tau 1 = 55 microseconds, tau 2 = 220 microseconds and tau 3 = 1 ms) for the D96N mutant of bR. A component with tau = 1 ms was found to be present in the photocycle of the wild-type bacteriorhodopsin as a lag-phase in the relaxation of photoresponses at 400 and 520 nm. In the presence of Lu3+ ions or 80% glycerol this component was clearly seen as an additional phase of M-formation. The azide effect on the D96N mutant of bR suggests that the 1-ms component is associated with an irreversible conformational change switching the Schiff base from the outward to the inward proton channel. The maximum of the difference spectrum of the 1-ms component of D96N bR is located at 404 nm as compared to 412 nm for the first two components. We suggest that this effect is a result of the alteration of the inward proton channel due to the Asp96-->Asn substitution. Proton release measured with pyranine in the absence of pH buffers was identical for the wild-type bR and D96N mutant and matched the M-->M' conformational transition. A model for M rise in the bR photocycle is proposed. PMID- 1446745 TI - Specific antiviral activities of the human alpha interferons are determined at the level of receptor (IFNAR) structure. AB - Differences in activity among the family of human IFNs alpha are much reduced if these ligands are assayed on bovine cells. In particular, the activity of IFN alpha D is much higher on bovine than on human cells. To examine these differences, the bovine counterpart of the human IFNAR has been cloned and expressed in a human cell line. The transfected cell line now recognizes the human IFN alpha D as a high-specific-activity IFN subtype, indicating that the differences in sensitivity between the bovine and human cells to the human IFN alpha lie in the structure of the IFNAR chain rather than in the other components of the functional receptor. PMID- 1446746 TI - In vitro biosynthesis of lactase in preweaning and adult rabbit. AB - Lactase is synthesized as a high-mannose large precursor (200 kDa) which is subsequently complex-glycosylated (215 kDa) and split into the 150 kDa mature form. The regulatory mechanisms responsible for the decline of activity at weaning are not yet known. We have set up in vitro cultures of intestinal mucosa from suckling and adult rabbit and found that suckling and adult animals synthesize the same four forms of lactase-phlorizin hydrolase (LPH) but with a different distribution. In the proximal adult small intestine there is very little 180 kDa form, which is most probably a product of the 215 kDa complex glycosylated precursor. The 180 kDa form comprises a greater percentage of total LPH in the middle of the small intestine in adult and particularly in suckling rabbits. In the latter tissue this form is apparently more stable than in the adult tissue. Posttranscriptional control of lactase synthesis is therefore different in the various parts of the adult small intestine, and it is different in the suckling as compared to adult tissue. PMID- 1446747 TI - The levels of lactase and of sucrase-isomaltase along the rabbit small intestine are regulated both at the mRNA level and post-translationally. AB - We determined along the small intestine of young and adult rabbits the activities of lactase (LPH) and sucrase (SI), the levels of their cognate mRNAs, and examined the in vitro biosynthesis of LPH and pro-SI. Lactase activity is low in the proximal 1/3 of the intestine, whereas the mRNA levels are high. However, the rates of biosynthesis of the LPH forms correlated well with the steady-state levels of LPH mRNA in all segments, indicating that factor(s) acting post translationally produce a decline in brush border LPH in the proximal small intestine. These factor(s) are not involved in the processing of pro-LPH to mature LPH, since the relative amounts of the various forms of LPH are almost the same along the small intestine. Unexpectedly, we find that also for SI the ratio of activity to mRNA is low in proximal intestine. The biosynthesis of pro-SI correlates with the steady-state levels of its mRNA. Hence, the steady-state levels of LPH and SI along the small intestine are regulated both by mRNA levels and by posttranslational factor(s). PMID- 1446749 TI - Enflurane is a potent inhibitor of high conductance Ca(2+)-activated K+ channels of Chara australis. AB - The volatile anaesthetic, enflurane, is commonly used in surgery for inducing the state of general anaesthesia. It is assumed, that general anaesthetics act on ion channels, but little is known of how they do so and what kinds of channels are sensitive. We found, that enflurane inhibits a large conductance Ca(2+)-activated K+ channel of the green alga, Chara australis. Effects occur at clinically relevant concentrations are fully reversible. The actions of enflurane are distinct from those of charybdotoxin and tetraethylammonium, which are well known blockers of this channel type. Kinetic analysis of single-channel data demonstrates multiple effects of enflurane on the channel protein. PMID- 1446748 TI - Maturation of human lactase-phlorizin hydrolase. Proteolytic cleavage of precursor occurs after passage through the Golgi complex. AB - Maturation of human intestinal lactase-phlorizin hydrolase (LPH) requires that a precursor (pro-LPH) be proteolytically processed to the mature microvillus membrane enzyme (m-LPH). The subcellular site of this processing is unknown. Using low-temperature experiments and brefeldin A (BFA), intracellular transport was blocked in intestinal epithelial cells. In Caco-2 cells incubated at 18 degrees C, pro-LPH was complex-glycosylated but not cleaved, while at 20 degrees C small amounts of proteolytically processed LPH were observed. These data exclude a pre-Golgi proteolytic event. BFA completely blocked proteolytic maturation of LPH and lead to an aberrant form of pro-LPH in both Caco-2 cells and intestinal explants. Therefore, proteolytic processing of LPH is a post-Golgi event, occurring either in the trans-Golgi network, transport vesicles, or after insertion of pro-LPH into the microvillus membrane. PMID- 1446750 TI - C-type natriuretic peptide in bovine chromaffin cells. The regulation of its biosynthesis and secretion. AB - We report here the regulation of the biosynthesis and the secretion of C-type natriuretic peptide (CNP) in cultured bovine chromaffin cells. The combined treatment with protein kinase A and -C activators induced a 6-fold increase of intracellular levels of CNP-(1-103). The biosynthesized CNP-(1-103) was co released with its mature forms, typically CNP-(51-103), upon stimulation by nicotine or depolarizing agents. This confirms the neuropeptidic character of this third member of the natriuretic peptide family, which might act as a neuromodulator or neurotransmitter. PMID- 1446751 TI - Specific cleavage of DNA at CG sites by Co(III) and Ni(II) desferal complexes. PMID- 1446752 TI - Inhibition by spermine of the inner membrane permeability transition of isolated rat heart mitochondria. AB - The effect of spermine on the permeability transition of the inner mitochondrial membrane of isolated rat heart mitochondria was evaluated. The permeability transition was triggered using a series of agents (t-butyl hydroperoxide, phenylarsine oxide, carboxyatractylate, and elevated Ca2+ and inorganic phosphate concentrations), and was monitored via Ca(2+)-release, mitochondrial swelling and pyridine nucleotide oxidation. By all three criteria, spermine inhibited the transition. A C50 of 0.38 +/- 0.06 (SD) mM was measured for inhibition. PMID- 1446753 TI - Screening for retinopathy of prematurity. PMID- 1446754 TI - Natural history of retinopathy of prematurity: a prospective study. AB - The natural history of retinopathy of prematurity (ROP) has been studied prospectively in 572 infants < or = 1,700 g birthweight using a protocol designed specifically to investigate the subtle features of this condition. Acute ROP developed in 50.9%. All ROP stages 1 and 2 underwent complete resolution and of the 27 (4.7%) infants with stage 3/4 disease, cicatricial sequelae developed in six. Incidence and severity increased with decreasing birthweight and gestational age. Onset was not confined to the temporal retina but exhibited a predilection to start first in the nasal retina of the most immature neonate. The vertical retinal regions were relatively spared. Retinal arteriolar tortuosity developed around three months postnatally and was related to ROP severity but not its presence. The age at onset and rate of progression of retinopathy were largely determined by the stage of development but were also modified by systemic and local factors. The relevance of these findings to ROP screening is discussed. PMID- 1446755 TI - Rational choice of therapy in primary open angle glaucoma. PMID- 1446756 TI - Ocular hypertension: correlation of anterior chamber angle width and risk of progression to glaucoma. AB - Twenty five patients with ocular hypertension (OH) and a narrow angle and 34 patients with OH and an open angle were followed for an average of six years. One eye of each patient had been randomly assigned to treatment with topical timolol. A shallow axial anterior chamber depth and a narrow angle (van Herick Grade 2 or less) was associated with the development of angle-closure glaucoma (ACG) in the narrow angle group, but the open angle group developed significantly more visual field loss. Nine patients (36%) in the narrow angle group developed ACG, and nine patients (26.5%) in the open angle group developed glaucomatous discs and field loss. The reduction in intraocular pressure due to topical timolol was equal in the narrow angle and the open angle groups, but topical timolol did not protect against the development of angle-closure glaucoma or visual field loss. PMID- 1446757 TI - Laser microsclerostomy for primary open angle glaucoma: a review of laser mechanisms and delivery systems. AB - A number of different lasers and delivery systems are currently used in experimental sclerostomy procedures. These are discussed with reference to their performance in terms of cutting accuracy and trauma to the adjacent tissues. Lasers emitting wavelengths close to the absorption peaks of water in the mid infrared region and organic polymers in the far ultraviolet region have a short absorption pathlength in the sclera and produce the least adjacent thermal tissue trauma. These ablating lasers cannot be delivered gonioscopically, and contact endoscopic techniques trap hot expanding gases within the forming sclerostomy channel causing secondary thermal and mechanical damage. Optimal results should be obtained using an ablating laser delivered either through an open mask or a modified endoscopic system incorporating an adequate exhaust mechanism. PMID- 1446758 TI - The association of iridoschisis and primary angle-closure glaucoma. AB - Twelve patients with iridoschisis in one or both eyes were studied to determine the clinical features of the condition and to examine the relationship of iridoschisis to primary angle-closure glaucoma. A spectrum of iris pathology, from subtle intrastromal atrophy to extensive splitting of the anterior layer of iris with fibrillar disintegration, was found in the affected and fellow eyes. Gonioscopy revealed partial or complete angle closure, particularly involving the superior angle, in all patients. Seven had glaucomatous disc damage and five had normal discs. The mean axial length and anterior chamber depth measurements in patients with iridoschisis were similar to those found in matched patients with primary angle-closure glaucoma but were significantly less than the measurements found in matched normals (p < 0.001). This study suggests that iridoschisis is an unusual manifestation of iris stromal atrophy and results from intermittent or acute elevation of intraocular pressure. Primary angle-closure glaucoma should be excluded in patients who present with iridoschisis. PMID- 1446759 TI - Doppler carotid artery studies in asymmetric glaucoma. AB - Doppler carotid artery studies were performed in 12 glaucoma patients with marked asymmetry in bilateral visual field loss. The resistance index and the pulsatility index of the internal carotid artery velocity waveforms were significantly greater on the same side as the eye with the greater visual field loss. The increased resistance to blood flow in the internal carotid artery on the side with advanced field loss might predispose the eye on this side to the effects of raised intraocular pressure by causing a reduction in the perfusion pressure at the optic nerve head. The role of ocular perfusion pressure in the pathogenesis of glaucoma is discussed. More extensive studies are necessary. PMID- 1446760 TI - Comparative evaluation of the Allergan Humphrey 570 and Canon RK-1 autorefractors: I. Objective autorefraction in normal subjects. AB - Fifty normal subjects were studied comparing objective autorefraction using the Allergan Humphrey 570 (AH 570) and Canon RK-1 autorefractors in terms of ease of operation, the time taken and their accuracy compared with clinical refraction. Both the autorefractors were equally easy to operate but the AH 570 was quicker. Objective autorefraction with the AH 570 was more accurate than using the Canon RK-1 especially with respect to spherical equivalence, sphere power and cyclinder axis: approximately 80% of the values were within 0.51 dioptres or 11 degrees of clinical refraction compared to approximately 60% for the Canon RK-1. The possible reasons for the superior performance of the AH 570 are discussed. PMID- 1446761 TI - Comparative evaluation of the Allergan Humphrey 570 and Canon RK-1 autorefractors: II. Objective autorefraction in pseudophakes. AB - Fifty patients (50 eyes) with posterior chamber intraocular lenses and a best corrected visual acuity of at least 6/12 were studied. The Allergan-Humphrey 570 (AH-570) and Canon RK-1 autorefractors were compared in terms of ease of operation, time taken and their accuracy relative to clinical refraction. Both the autorefractors were equally easy to operate but the AH-570 was quicker. The AH-570 had a higher percentage of eyes within 11 degrees of clinically determined cylinder axis while the Canon RK-1 had a higher percentage of patients within 0.51 diopters of spherical equivalence, sphere power and cylinder power as determined by clinical refraction. This difference in the accuracy of objective autorefraction was not statistically significant; the clinical significance is uncertain. PMID- 1446762 TI - The effects of adrenaline, hyaluronidase and age on peribulbar anaesthesia. AB - In a prospective, randomised, masked trial, 91 patients undergoing intraocular surgery received an anaesthetic mixture containing lignocaine hydrochloride 2% and bupivacaine hydrochloride 0.5%. In addition group 1 had hyaluronidase (50 i.u./ml) and adrenaline (1:200,000), group 2 had hyaluronidase alone, group 3 had adrenaline alone and group 4 had neither. The groups were compared regarding the quality of operating conditions. Hyaluronidase had a substantial beneficial effect though there was no significant difference related to the use of adrenaline. Anaesthesia was less effective in patients under the age of 65 years. PMID- 1446763 TI - Peribulbar anaesthesia: failure to abolish the oculocardiac reflex. AB - Peribulbar anaesthesia is a form of regional anaesthesia which has been used with increasing popularity in cataract surgery. Recently indications for its use have been extended to include surgery for vitreo-retinal disease and strabismus. This study shows that in nine of 11 patients in whom the oculocardiac reflex was stimulated by traction on an extra-ocular muscle, peribulbar anaesthesia failed to abolish the reflex. In each of these patients, the reflex manifested as a bradycardia. In one subject, the bradycardia was profound, showing no QRS complex for five seconds. We recommend that cardiac rhythm be monitored throughout procedures performed under peribulbar anaesthesia, and that a vagolytic agent be available for immediate use. PMID- 1446764 TI - Extracapsular cataract extraction in diabetics with rubeosis iridis. AB - We reviewed thirteen operated eyes (twelve diabetic patients) with rubeosis iridis who underwent extracapsular cataract extraction and intraocular lens implantation. Prior to surgery five had active proliferative retinopathy (APR), and eight had non-proliferative retinopathy (NPR), either quiescent proliferative retinopathy (QPR) or background retinopathy (BR). No case with APR was visually improved by surgery. Three cases with NPR achieved a visual acuity of 6/12. After surgery, vitreous haemorrhage or progression of proliferative retinopathy occurred in three cases with APR. Early postoperative fibrinous uveitis was severe in eyes with APR, resulting in permanent fibrin membrane formation in four. We suggest a significant prognostic indicator in diabetic cataract extraction with rubeosis iridis is the status of the underlying retinopathy. With NPR, postoperative visual acuity may be good and early postoperative complications less severe. In the presence of APR the visual outcome is poor, progression of retinopathy likely and early postoperative fibrinous uveitis may be severe enough to prevent postoperative panretinal photocoagulation. Maximum preoperative panretinal ablation is essential in these cases. PMID- 1446765 TI - Occlusion for amblyopia: a comprehensive survey of outcome. AB - The results of a long term follow up of all patients from a single health district started on occlusion for amblyopia in 1983 are reported. Three hundred and sixty-eight patients started treatment, their average age was four years seven months, the average amount of daily occlusion was 1.5 hours and the average length of follow up was 31 months. 37% of cases achieved a final visual acuity of 6/9 or better and another 33% a visual acuity of 6/12 or 6/18.23% did not achieve 6/18 and treatment of these patients was regarded as failure. Data for the remainder (7%) were incomplete. The success rate of occlusion treatment varied little with the age of starting treatment. The group with combined strabismus and anisometropia responded least well to treatment. PMID- 1446766 TI - Factors related to the final visual outcome of 425 patients with traumatic hyphema. AB - A retrospective study of the visual outcome of 425 in-patients with traumatic hyphaema has been conducted. A multivariate analysis demonstrated that after adjusting for age, sex and pre-existing poor vision, the size of hyphaema on presentation and the presence of retinal damage were significant predictors of a worse final visual outcome (p = 0.00003 and 0.00001 respectively). Topical steroid and/or cycloplegic medication, and the occurrence of secondary haemorrhage did not influence the final visual outcome after adjustment for the other variables. These data illustrate, in an unselected sequential population of patients, the role of these factors in terms of final visual outcome following hyphaema from blunt ocular trauma. PMID- 1446767 TI - Factors related to the incidence of secondary haemorrhage in 462 patients with traumatic hyphema. AB - In a retrospective study of 462 in-patients with traumatic hyphema, secondary haemorrhage occurred in 8.7% of patients. A multivariate analysis demonstrated that the size of hyphaema on presentation and the presence of retinal damage did not affect the probability of secondary haemorrhage. The incidence of secondary haemorrhage was found to decrease by approximately half with the use of topical steroid (p = 0.005), but did not appear to be influenced by the use of cycloplegics. These data indicate in an unselected sequential population of patients, the therapeutic importance of topical steroid in the treatment of blunt ocular trauma. PMID- 1446768 TI - Transient vessel wall sheathing in acute retinal vein occlusions. AB - Three cases are reported which had features similar to, and evolved in a pattern consistent with central retinal vein occlusions and a fourth case is reported which behaved as a hemispheric vein occlusion. However, they differed from classic retinal vein occlusions by having prominent sheathing of the retinal venous vasculature at presentation, which in all four cases resolved within three weeks. There was no evidence for any of these cases having an inflammatory vasculitis. The significance of this transient sheathing is uncertain. PMID- 1446769 TI - Migrating scleral explants. AB - Anterior migration of an extrascleral explant is an uncommon complication following buckling procedures. We report five patients where the explant cheesewired through the rectus muscle insertion following retinal detachment surgery. Muscles were not disinserted at the time of surgery in any case. Ocular motility problems were only seen in two patients. The probable mechanisms of this hitherto unreported complication are discussed. PMID- 1446770 TI - The Purkinje vascular entoptic test: a halogen light gives better results. AB - The Purkinje vascular entoptic test is a test of macular function which employs a light directed through the sclera illuminating the fundus. This light casts shadows of retinal blood vessels on to posterior pole photoreceptors. When the light source is moved, a patient with a good macular function should be able to see a negative image of his or her retinal blood vessels. We evaluated the Purkinje test in eyes with clear ocular media. A bright 3.5 watt halogen rechargeable transilluminator was used instead of a pen torch as previously described. Sixty-eight patients (129 eyes) attending a diabetic eye clinic, were tested. The test correctly identified 91% of eyes with good macular function and 77% of eyes with poor macular function (visual acuity 6/24 or poorer). If a vascular pattern was seen, it was probable (0.89) that good macular function was present. If no vascular pattern was seen, it was probable (0.80) that the eye had poor macular function (chi 2 = 60.14, P = < 0.001). Our results were superior to those previously reported. We attribute the increased accuracy of our test to the brighter light source used. PMID- 1446771 TI - Primary lymphoplasmacytoma of the conjunctiva. AB - We report the case of an 80-year-old patient with isolated lymphoplasmacytoma of the conjunctiva. Only five other such cases have been previously reported in the literature. In all six patients, the disease remained limited and no sign of systemic disease could be found after prolonged follow-up. As isolated plasmacytoma of the conjunctiva seems to be benign, treatment of such tumours should be conservative. PMID- 1446772 TI - Ocular manifestations of Noonan syndrome. AB - Noonan syndrome is a genetic condition inherited in an autosomally dominant manner, characterised by congenital heart disease, short stature, abnormal facies and the somatic features of Turner's syndrome, but a normal Karyotype. The ophthalmological and orthoptic findings on 58 patients with Noonan syndrome are reported. External features were hypertelorism (74%), downward sloping palpebral apertures (38%), epicanthic folds (39%) and ptosis (48%). The orthoptic examination revealed strabismus in 48%, refractive errors in 61%, amblyopia in 33%, and nystagmus in 9% of cases. Sixty-three per cent of cases had anterior segment changes consisting of: Prominent corneal nerves (46%), anterior stromal dystrophy (4%), cataracts (8%) and panuveitis (2%). Fundal changes occurred in 20% of the study group, including optic nerve head drusen, optic disc hypoplasia, colobomas and myelinated nerves. Forty-seven per cent required non surgical treatment and a further 16% had undergone surgery for strabismus or ptosis. Only three patients had no visual defects. With such a high incidence of ophthalmic abnormalities it is clearly important that children with Noonan syndrome are screened by an ophthalmologist at an early age. PMID- 1446773 TI - Conjunctival lymphoedema in Turner's syndrome. PMID- 1446774 TI - Prostaglandin E2 (PGE2) differentially regulates the production of IL-2 and IL-3 by murine immune T-cells. AB - Eicosanoids are important mediators of inflammation, and have been shown to have potent, and usually suppressive immunoregulatory activities. In the paper, we have examined the role of prostaglandin (PGE2) production in the regulation of two cytokines, IL-2 and IL-3, which both play a key role in contact sensitivity and delayed type hypersensitivity reactions. In agreement with previous studies, we demonstrate that prostaglandins down-regulate IL-2 production in the system. Unexpectedly, however, IL-3 levels are enhanced in the presence of the prostaglandin PGE2 and conversely, are inhibited by treatment with aspirin, a potent inhibitor of prostaglandin metabolism. The implications of this result in terms of the immunoregulatory role of PGs will be discussed. PMID- 1446775 TI - Enzyme ultracytochemical demonstration of Ca(++)-ATPase in the rat cerebral cortex. AB - The localization of Ca(++)-ATPase activity was investigated in the rat cerebral cortex using an ultracytochemical method. Our cytochemical procedure for the detection of enzyme activity is based on an incubation medium consisting of tricine buffer, ATP-disodium salt as substrate, cerium chloride as capturing agent, CaCl2, and levamisole as a nonspecific alkaline phosphatase inhibitor. Final pH was 7.4. Reaction products showing Ca(++)-ATPase activity were localised on the pre- and postsynaptic plasma membrane in association with synaptic vesicles, postsynaptic dendrites and on the axolemma in myelinated nerve fibres. The verification of the main enzymatic properties of Ca(++)-ATPase localization activity is the subject of the following report. PMID- 1446776 TI - In vitro enhanced destruction of erythrocytes as a result of their chlorination. AB - Subarachnoidal haemorrhage is followed by accumulation of granulocytes and macrophages in cerebrospinal fluid (CSF). As a result erythrocytes are destroyed and removed from CSF. Activated granulocytes chlorinate many species including erythrocytes. It has been shown that chlorinated erythrocytes are more sensitive to phagocytosis by macrophages than the native ones. PMID- 1446777 TI - Differentiated reaction of different types of antheridial cells in Chara vulgaris to the changes in light conditions during 24 hours. AB - Circadian rhythm of activity of 3H-leucine incorporation into antheridial cells of Chara vulgaris, in natural photoperiod was compared with changes in mitotic activity of antheridial filament cells which form spermatozoids. Three types of cells functionally connected with each other i.e. manubria, capitular cells and antheridial filaments indicate high amplitude (80-90%) changes in circadian translational activity and some similarities in their course. The shield cells are characterized by small circadian changes in translational activity in the range of 15-30% and their different rhythm. Manubria, which are the secretive cells indicated the highest dependence of the dynamic of translational activity on the time of day. Their high activity overlaps light phase, low activity--dark phase. The reaction of capitular cells to day/night change is delayed in comparison with the reaction of manubria, and that of antheridial filaments is delayed in comparison with the capitular cells reaction. The assumption was set forth that manubria play the role of oscillators (starttercells) which induce the wave of changes translocating to the other cells functionally and spatialy connected with them. The course of the wave of antheridial filaments mitotic activity suggests that a distinct drop in MI in the morning may be the result of the lack of the factors necessary for initiation of the mitosis, dependent on light-induced high translational activity of antheridial cells. PMID- 1446778 TI - A comparison of the proliferative activity of astrocytes and astrocyte-like cells expressing vimentin in the injured mouse cerebral hemisphere. AB - After an unilateral injury of the cerebral hemisphere, 28 nice were injected with 3H thymidine at different intervals following the injury. Thereafter, the distribution of autographically labelled astrocytes expressing glial fibrillary protein (GFAP) and astrocyte-like cells expressing vimentin were recorded within the region of injury. Proliferative activity of the two cell types started at the same time, i.e. 24 h. after injury, reached its maximum on day 4, and returned to normal level after the 8th posttraumatic day. However, on day 4 the number of proliferating GFAP-positive astrocytes was about 50% higher than that of vimentin positive cells. This was regarded as a proof of the concept that a significant number of astrocytes did not express vimentin during its mitotic cycle. Those facts were considered as an evidence against the hypothesis that a reactive astrocyte division induces a two-stage increase in the cytoskeletal proteins level with the elevated synthesis of vimentin preceding that of GFAP. PMID- 1446779 TI - LH as a modulator of cytoskeleton arrangement and steroidogenic function in Leydig cells in vitro. PMID- 1446780 TI - Transfected endometrial cultured cells: a system to study gene-regulation by estrogens. AB - Glandular epithelial (GE) and stromal cells were isolated from guinea-pig endometrium, cultured and subcultured separately. At the end of subculture, the purity of each cell population was higher than 95% and cells displayed a high level of estrogen receptors. Calcium phosphate transfection conditions were defined using a control plasmid containing the bacterial CAT gene driven by viral promoter and enhancer sequences. Transfection experiments were performed with other plasmids in which CAT gene was linked to different estrogen response elements (EREs) derived from those of vitellogenin genes. CAT activity was significantly increased by estradiol-17 beta treatment only when GE or stromal cells were transfected with plasmids containing EREs previously reported as functional EREs in other cell types. This induction was abolished by ICI 164,384 diethylstilbestrol was as effective as estradiol-17 beta for CAT induction and estradiol-17 alpha was ineffective. Transiently transfected endometrial cells in subculture are a suitable system to study the estrogen effect on gene regulatory elements. PMID- 1446781 TI - Single and dual hormone secretors in GH3 cultures respond differently to hypothalamic factors. AB - Recent studies using both normal and tumoral pituitary cell cultures have demonstrated that growth hormone (GH) and prolactin (PRL) secreting populations contain cells which release either one or both of these hormones. In order to determine whether these two cell types can be differentially regulated by hypothalamic factors we performed the following study employing plaque assays for GH and PRL. Using cultures of GH3 cells, a rat tumor cell line which contains both of these cell types, we found that the hypothalamic factors vasoactive intestinal peptide (VIP) and thyrotropin releasing hormone (TRH) when used together had a greater influence on plaque formation than when each was used individually. This suggested that cells were present in culture that responded to one peptide but not the other. Estradiol-treated cultures (which contain only dual-secreting cells) were then evaluated for VIP and TRH responsiveness and found to respond to TRH but not VIP. Finally, we assessed the peptide sensitivity of cultures that were exposed to a conjugate of VIP and the A-chain of ricin (a potent cytotoxin). In addition to eliminating VIP-responsive cells, this treatment markedly reduced the proportions of cells secreting GH-only while having no appreciable influence on dual-hormone secretors. When taken together, our findings indicate that single and dual secretors respond differently to at least two hypothalamic secretagogues and suggest that regulatory differences between these cell types may be important in the control of GH and PRL secretion. PMID- 1446782 TI - Autoinduction of thyroid hormone receptor during metamorphosis is reproduced in Xenopus XTC-2 cells. AB - To determine if the autoinduction of thyroid hormone receptor (TR) alpha and beta mRNAs during metamorphosis in Xenopus tadpoles can be reproduced in cultured cells, we have screened four Xenopus cell lines (XTC-2, XL-177, XL2 and Kr) for receptor transcripts and their response to thyroid hormone. Exposure of XTC-2 cells to 10(-9) M triiodothyronine (T3) for 24 h upregulated TR alpha and beta mRNAs by 2-4- and 10-40-fold, respectively. In view of the marked similarity of the differential distribution of the two transcripts and their upregulation by T3 to the pattern of autoinduction seen in whole tadpoles, the process was studied in greater detail in XTC-2 cells. The time-course of autoinduction of TR alpha and beta mRNAs in these cells also resembled that in vivo, the two transcripts being significantly induced by 3-6 h after T3. Dose-response to T3, and the relative responses to its active and inactive analogs, confirmed that the process of autoinduction was initiated by thyroid hormone receptor with the same functional characteristics as that found in all amphibian and mammalian tissues. Experiments performed with cycloheximide suggested that intermediary protein(s) were involved in autoinduction, so that TR genes cannot be considered as 'immediate early' genes for this process. The possible advantages of studying thyroid hormone action in metamorphosis in XTC-2 cells are briefly discussed. PMID- 1446783 TI - Isolation of luteinising hormone receptor binding inhibitor from bovine corpus luteum. AB - A luteinising hormone receptor binding inhibitor (LHRBI) has been purified from bovine corpus luteum (CL). Steroid-free extract of the CL was subjected to successive chromatographies on Sephadex G-50, Q-Sepharose, Orange A dye and metal chelate affinity columns followed by high performance-reverse phase and gel filtration columns. Purification was monitored by the ability of the fractions to inhibit the binding of 125I-human chorionic gonadotropin (hCG) to porcine granulosa cells in vitro. The final isolate showed an 8000-fold enrichment of activity. It was also capable of inhibiting porcine granulosa cell secretion of estradiol and progesterone (P) in vitro. Administration of LHRBI into follicle stimulating hormone (FSH)-stimulated, immature rats strongly inhibited the ovarian ovulatory response to hCG as revealed by decreased P levels and the number of ova released. The M(r) of LHRBI as assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis was ca. 15 kDa and the pI was between 5.0 and 5.5. PMID- 1446784 TI - Identification of G protein alpha subunit mutations in human growth hormone (GH)- and GH/prolactin-secreting pituitary tumors by single-strand conformation polymorphism (SSCP) analysis. AB - We have applied the polymerase chain reaction (PCR) and single-strand conformation polymorphism analysis (SSCP) to detect activating mutations in the Gs alpha subunit gene, amplifying genomic DNA extracted from growth hormone (GH)- and GH/prolactin (PRL)-secreting human pituitary tumors. Of 15 tumors tested six contained mutations in the analyzed regions of the Gs alpha. SSCP analysis revealed band shift in exon 8 in four GH- and in one GH/PRL-secreting tumors, and in exon 9 in one GH/PRL-secreting tumor. Direct sequencing of PCR reaction products identified the mutations as R201-H, R201-S and R201-C in exon 8 and Q227 L in exon 9. These results show the efficacy of PCR/SSCP analysis in the detection of G protein mutations and extend the generalization that these sites are hot spots in tumor-inducing mutations. PMID- 1446785 TI - Thyroid hormone stimulates glucose transport and GLUT1 mRNA in rat Sertoli cells. AB - The transport of 2-deoxyglucose (dGlc) by cultured rat Sertoli cells was stimulated by L-triiodothyronine (T3) in a time and dose-dependent manner. The lag-time was of about 6 h, the half-maximal dose (ED50) was 0.47 nM, which correlates with the Kd of the nuclear T3 receptor of rat Sertoli cells (Kd = 1-2 nM), and the stimulation was maintained up to 24 h. The effect was specific, as judged by the order of potency of T3 analogs. Cycloheximide prevented the stimulatory effect without affecting the basal uptake. T3 stimulated the uptake of the glucose analog 3-O-methylglucose (MeGlc) with the same order of potency as that of dGlc. The ontogenetic profile of the T3 effect coincides with that of T3 nuclear receptors in rat Sertoli cells. Northern blot analysis demonstrated that Sertoli cells express the erythrocyte/brain glucose transporter isoform (GLUT1) but not the adipose/muscle isoform (GLUT4). T3 treatment (10(-7) M for 24 h) induces an increase of GLUT1 mRNA level comparable to that of glucose analog uptake. These results suggest that thyroid hormone stimulates glucose transport by increasing the synthesis of new glucose transporter units and give further evidence for a direct effect of thyroid hormone in the modulation of Sertoli cell functions. PMID- 1446786 TI - Membrane transport of thyroid hormone in the human choriocarcinoma cell line, JAR. AB - We studied uptake of L-triiodothyronine (T3) by the human choriocarcinoma cell line, JAR. Uptake was time dependent with a half-time of 56.2 +/- 7.2 min (mean +/- SEM, n = 4). A non-saturable component accounted for about 24% of total uptake. We found a single saturable uptake mechanism with a calculated Michaelis constant (Km) of 586 +/- 206 nM (n = 9) and a corresponding maximum velocity of 17.0 +/- 5.7 pmol/min per mg protein (n = 9), values similar to those we have described recently in cultured normal human trophoblast cells. Uptake was dependent on temperature and intracellular energy, being reduced at lower temperatures and in the presence of potassium cyanide. It was independent of the Na+ gradient across the cell membrane and the presence of Na+ in the external medium, but was affected by the cell membrane potential. PMID- 1446787 TI - A distal region enhances the prolactin induced promoter activity of the rabbit alpha s1-casein gene. AB - Casein gene expression is induced in the rabbit mammary gland by prolactin (PRL). alpha s1-casein is the major casein secreted into milk. In order to define the position of the DNA sequences involved in the control of rabbit alpha s1-casein gene regulation by PRL, chimeric genes were constructed between upstream regions of the rabbit alpha s1-casein gene and the chloramphenicol acetyl transferase (CAT) reporter gene. A series of 5'-deleted fusion genes was obtained by nuclease digestion of the alpha s1-casein gene upstream region. These gene constructs were transfected into rabbit primary mammary cells, or cotransfected in CHO cells with the plasmid coding for the rabbit mammary receptor (PRL-R). A regulatory region has been located between nt -3768 and -3155. This region enhances the prolactin induced promoter activity of the alpha s1-casein gene. It might possess or cooperate with prolactin responsive elements located further downstream in the alpha s1-casein gene. PMID- 1446788 TI - Role of local environmental factors in determining tissue-specific effects of estrogen: examination of uterine tissues transplanted to brain. AB - Estrogen stimulates uterine epithelial cells to divide, but not estrogen concentrating neurons in the adult brain. This effect correlates with recent evidence that estrogen can induce the expression of certain growth-related genes in uterus which are not directly induced by estrogen in the adult brain. The possibility that local diffusible factors play a major role in determining tissue specific effects of estrogen was examined by transplanting uterine tissues into the brain, muscle and kidney of adult rats and then comparing the effects of estrogen on the incorporation of [3H]thymidine and the expression of Fos-, cdc2- and Rb-like immunoreactivity (IR) on native and transplanted uterine tissues, as well as in estrogen-concentrating regions of the brain adjacent to the uterine grafts. In native uteri, estrogen treatment stimulated Fos-, cdc2-, and Rb-like IR, as well as [3H]thymidine incorporation, within lumenal and glandular epithelial cells. All of these effects were estrogen responsive--no immunoreactive staining within uterine epithelial cells and no signs of epithelial cell proliferation were observed in the native uteri of non-estrogen treated animals. When uterine tissues were transplanted to brain, Fos-, cdc2-, and Rb-like IR epithelial cells, as well as many [3H]thymidine-incorporating uterine epithelial cells, were observed in all estrogen-treated animals and in some non-estrogen-treated animals as well. Identical results were obtained when uterine tissues were transplanted to skeletal muscle, but not to kidney (in the kidney, transplanted epithelial cells expressed all four parameters but only in estrogen-treated animals, comparable to the native uterus). In contrast, estrogen did not stimulate cell division and did not induce Fos-, cdc2-, or Rb-like IR within estrogen-concentrating neuronal regions of the ventromedial hypothalamus. In addition, the presence of uterine tissue in the brain did not confer the ability of estrogen to stimulate any of these parameters within nearby, estrogen concentrating regions. These data suggest that there are factors in brain and muscle which can allow uterine epithelial cells to divide in the absence of estrogen. There was no evidence of a diffusible factor in brain which inhibits uterine epithelial cell division, nor of a diffusible factor in uterus which can confer estrogenic stimulation of growth-related genes and cell division to central nervous system neurons. In addition, the data provide the first evidence for estrogen regulation of cdc2 and Rb expression in normal uterus. PMID- 1446789 TI - Thyroid hormone response of slow and fast sarcoplasmic reticulum Ca2+ ATPase mRNA in striated muscle. AB - The thyroid status markedly influences the contractile function of muscle, and changes in the activity of the Ca2+ ATPase of the sarcoplasmic reticulum (SR) contribute to these alterations. Two separate genes encode the major isoforms of SR Ca2+ ATPase. In fast skeletal muscle, sarcoplasmic endoplasmic reticulum Ca2+ ATPase type 1 (SERCa1) presents the major isoform, whereas in slow skeletal muscle SERCa type 2 (SERCa2) predominates. Cardiac muscle contains only SERCa2. To examine the mechanisms responsible for changes in contractile function, we quantitated SERCa1 and SERCa2 mRNA levels in fast extensor digitorum longus muscle (EDL), slow soleus muscle, and cardiac muscle in rats of different thyroid status. Hypothyroidism led in soleus to a marked decrease in SERCa1 mRNA and SERCa2 mRNA levels, in cardiac muscle SERCa2 mRNA decreased markedly, as previously shown by us, and in EDL SERCa1 mRNA decreased. These findings are compatible with a hypothyroidism induced decrease in SR Ca2+ ATPase activity and a delay in muscle relaxation. In contrast, SERCa2 mRNA of EDL, representing only a small percent of total SERCa mRNA in this muscle, increased to 175% of control values. Muscle specific and SERCa gene specific changes also occur after acute triiodothyronine (T3) administration to hypothyroid rats. T3 does not induce a significant change in SERCa1 or SERCa2 mRNA levels in soleus, but in the heart SERCa2 mRNA increases about 3-fold. In EDL, T3 increases SERCa1 mRNA from a hypothyroid level of 59 +/- 6% to 138 +/- 4% of control values but SERCa2 mRNA is decreased to 75 +/- 5% of control levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446790 TI - A synthetic peptide corresponding to amino acids 9-30 of the extracellular domain of the follitropin (FSH) receptor specifically binds FSH. AB - As deduced on the basis of cloning experiments, the putative extracellular domain of pituitary glycoprotein hormone (lutropin (LH), thyrotropin (TSH), and FSH) receptors (rec) is sufficiently large to suggest involvement in hormone binding. Comparison of the amino acid sequences of the extracellular domains of the glycoprotein hormone receptors indicates that the FSH receptor has a peptide sequence in the external domain close to the amino terminus (residues 9-30) which has no sequence homology to receptors for LH or TSH. To examine whether this region is involved in FSH-receptor interaction, we studied the hormone-binding properties of a corresponding synthetic peptide in several systems. (1) Binding of 125I-hFSH to receptor-containing bovine testis membranes was inhibited by preincubation with FSH rec-(9-30) peptide amide in a concentration-dependent manner. (2) 125I-labeled rec-(9-30) peptide amide bound to ovine, bovine, or human FSH preparations, and the binding was inhibited by solubilized bovine FSH receptor. 125I-labeled rec-(9-30) peptide amide, however, did not bind to LH or TSH. (3) 125I-hFSH bound to unlabeled rec-(9-30) peptide amide, and the binding was inhibited by excess unlabeled FSH, but not by LH or TSH. (4) Scatchard analysis indicated that the FSH rec-(9-30) peptide amide contained a single class of FSH binding sites with a Ka = 1.1 x 10(6) M-1. (5) The binding of 125I-labeled rec-(9-30) peptide amide to hFSH, bFSH or oFSH was effectively inhibited by rabbit polyclonal antibodies raised against rec-(9-30) peptide amide but not by preimmune rabbit serum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446791 TI - Perspectives in diabetes. Islet transplantation with immunoisolation. AB - Immunoisolation is a potentially important approach to transplanting islets without need for immunosuppressive drugs. Immunoisolation systems have been conceived in which the transplanted tissue is separated from the immune system of the host by an artificial barrier. These systems offer a solution to the problem of human islet procurement by permitting use of islets isolated from animal pancreases. The devices used are referred to as biohybrid artificial organs because they combine synthetic, selectively permeable membranes that block immune rejection with living transplants. Three major types of biohybrid pancreas devices have been studied. These include devices anastomosed to the vascular system as AV shunts, diffusion chambers, and microcapsules. Results in diabetic rodents and dogs indicate that biohybrid pancreas devices significantly improve glucose homeostasis and can function for more than a year. Recent progress made with this approach is discussed, and some of the remaining problems that must be resolved to bring this technology to clinical reality are addressed. PMID- 1446792 TI - Experimental transplantation with principal islets of teleost fish (Brockmann bodies). Long-term function of tilapia islet tissue in diabetic nude mice. AB - Certain teleost fish have macroscopically visible islets called BBs that are anatomically discrete. BBs were harvested from Oreochromis nilotica (tilapia) with microscissors, divided, and cultured overnight at 37 degrees C before transplantation into STZ-induced diabetic nude mice. Each mouse received BB fragments from 3-5 fish weighing in aggregate approximately 1.7 kg. Non-FPGs were monitored 5 days/wk. Recipients remained normoglycemic (plasma glucose < 11.1 mM) for 50 days posttransplantation. Mice bearing 50-day-old grafts had essentially normal GTTs. Left nephrectomies then were performed to remove the grafts, and plasma glucose levels in recipient mice rose to > 22.2 mM. Histological examination of graft-bearing kidneys showed viable, vascularized islet tissue containing numerous well-granulated beta-cells; examination of recipient native pancreases revealed small islets composed predominantely of non-beta-cells. PMID- 1446793 TI - Induction of resistance to endothelin-1's biochemical actions by elevated glucose levels in retinal pericytes. AB - Because retinal pericytes have contractile properties and are affected by diabetes, we have studied the responsiveness of pericytes to ET-1, a potent vasoconstrictor, in the presence of various concentrations of glucose. Cultured calf retinal pericytes were exposed to glucose levels of 5.5 or 25 mM for up to 8 days. Radioreceptor studies that used [125I]ET-1 showed that pericytes contained high-affinity binding sites with Kd of 3 x 10(-10) M, and these binding affinities were unaffected by glucose concentration. Receptor number appears to be elevated, but this increase was NS. Responsiveness of pericytes to ET-1 was studied with respect to stimulation of DAG and IP3 levels and PKC activities. In contrast to receptor binding, exposure to 25 mM glucose for > 6 days blunted pericyte responsiveness to ET-1. The time course of ET-1 stimulation as measured by [3H]glycerol labeling, and IP3 level showed a 98% increase in [3H]DAG at 10 min and a fourfold increase for IP3, respectively. Cells exposed to 25 mM glucose only had a 32% increase for DAG, and no increase for IP3 was observed. Dose response studies on the stimulation of [3H]DAG increase showed the range of ET 1's effect to be between 10(-9) and 10(-7) M. At maximum, cells exposed to 5.5 mM glucose had a 70% increase versus only a 30% increase in those exposed to 25 mM glucose. Similarly, ET-1 only increased the total DAG levels in pericytes exposed to 5.5 mM glucose by 41%. PKC activity also was measured because DAG is one of its cellular activators.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446794 TI - Pathogenic factors responsible for glucose intolerance in patients with NIDDM. AB - To define the pathogenic factors responsible for glucose intolerance in NIDDM, we estimated insulin secretory capacity, SI, and SG in 11 healthy, nondiabetic subjects and 9 NIDDM patients who had no SI impairment. All subjects studied were nonobese and normotensive. Each underwent a 75-g OGTT and a modified FSIGT: glucose was administered (300 mg/kg body weight), and insulin was infused (20 mU/kg over 5 min) from 20 to 25 min after the administration of glucose. SI and SG were estimated by Bergman's minimal-model method. The insulin response to oral glucose was significantly lower in NIDDM patients than in normal control subjects. First-phase insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 20 min was much smaller in NIDDM subjects (214 +/- 112 pM.min) than in control subjects (4643 +/- 885 pM.min, P < 0.01). SI was not statistically different in normal control subjects (1.27 +/- 0.18 x 10(-4) min-1.pM-1) versus diabetic patients (1.62 +/- 0.33 x 10( 4) min-1.pM-1). However, SG was significantly lower in diabetic subjects (1.11 +/ 0.17 x 10(-2) min-1) than in control subjects (2.35 +/- 0.26 x 10(-2) min-1, P < 0.01). These results suggest that impaired insulin secretion and decreased SG are the factors responsible for glucose intolerance of Japanese NIDDM patients with normal insulin sensitivity. Because SI and SG are the factors responsible for glucose intolerance of NIDDM patients with insulin resistance, it is conceivable that decreased SG is common in NIDDM patients regardless of their SI index. PMID- 1446795 TI - Lactate production and pyruvate dehydrogenase activity in fat and skeletal muscle from diabetic rats. AB - This study was initiated to explore the possibility that an increase in the supply of gluconeogenic precursors contributes to the overproduction of glucose by the liver in NIDDM patients. To address this issue, a form of experimental NIDDM was produced in rats by injecting a low dose (38 mg/kg) of STZ and comparing lactate and alanine production and PDH activity in skeletal muscle and isolated adipocytes from normal and diabetic rats. Skeletal muscle lactate production was measured by using a hindlimb perfusion technique and was significantly greater (P < 0.01) in the diabetic rats compared with two groups of control rats: one perfused at normal glucose levels and the other perfused at glucose concentrations comparable with those observed in diabetic rats. Alanine production by hindlimb from diabetic rats was 46% greater than hindlimbs from control rats perfused at normal glucose levels (P < 0.01) but was not significantly greater than control rats perfused at diabetic glucose levels. The percentage of glucose converted to lactate by muscle from both control groups was 4-5%, significantly lower than the 18% conversion rate observed in diabetic animals (P < 0.001). An increase in the ratio of lactate produced/glucose transport by isolated adipocytes from diabetic rats also was observed when measured in both the basal state (0.65 +/- 0.12 vs. 0.15 +/- 0.03, P < 0.01) and in the presence of maximal amounts of insulin (0.15 +/- 0.02 vs. 0.04 +/- 0.01, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446796 TI - Role of cytosolic Ca2+ in impaired sensitivity to glucose of rat pancreatic islets exposed to high glucose in vitro. AB - Sustained exposure to high concentrations of glucose selectively impairs the ability of pancreatic islets to secrete insulin in acute glucose stimulation. In order to evaluate the interrelationship between impaired insulin secretion and the dynamics of the cytosolic free Ca2+ level ([Ca2+]i), we have investigated the effect of high glucose exposure on both [Ca2+]i dynamics in single rat beta-cells and insulin release from rat pancreatic islets. Islets cultured at a high glucose concentration (16.7 mM) for 24 h showed significant reductions of the 16.7 mM GSIR compared with islets cultured at a normal glucose concentration (5.5 mM) (3.38 +/- 0.24 vs. 4.26 +/- 0.34%, respectively, P < 0.05). The capacity of glucose to raise the [Ca2+]i level also was significantly reduced in the beta cells maintained for 24 h at 16.7 mM glucose (P < 0.001). An additional culture in the medium with 5.5 mM glucose for 16 h restored both the GSIR and the [Ca2+]i response of islets cultured at high glucose. On the other hand, insulin release and [Ca2+]i rise in response to 20 mM L-Arg were well preserved. These observations confirm that exposure of pancreatic beta-cells to high glucose concentrations induces a selective reduction of the GSIR and, further, shows that this impaired response is reversibly restored by an additional culture with normal glucose. We also suggest that the inability of glucose to provoke a [Ca2+]i rise, which is observed in the beta-cells exposed to high glucose, may be responsible for the selective impairment of the GSIR. PMID- 1446797 TI - Insulin induces the translocation of GLUT4 from a unique intracellular organelle to transverse tubules in rat skeletal muscle. AB - Skeletal muscle surface membrane is constituted by the PM domain and its specialized deep invaginations known as TTs. We have shown previously that insulin induces a rapid translocation of GLUT4s from an IM pool to the PM in rat skeletal muscle (6). In this study, we have investigated the possibility that insulin also stimulates the translocation of GLUT4 proteins to TTs, which constitute the largest area of the cell surface envelope. PM, TTs, and IM components of control and insulinized skeletal muscle were isolated by subcellular fractionation. The TTs then were purified further by removing vesicles of SR origin by using a Ca-loading procedure. Ca-loading resulted in a five- to sevenfold increase in the purification of TTs in the unloaded fraction relative to the loaded fraction, assessed by immunoblotting with an anti-DHP receptor monoclonal antibody. In contrast, estimation of the content of Ca(2+) ATPase protein (a marker of SR) with a specific polyclonal antibody revealed that most, if not all, SR vesicles were recovered in the Ca-loaded fraction. Western blotting with an anti-COOH-terminal GLUT4 protein polyclonal antibody revealed that acute insulin injection in vivo (30 min) increased the content of GLUT4 (by 90%) in isolated PMs and markedly enhanced (by 180%) GLUT4 content in purified TTs. Importantly, these insulin-dependent changes in GLUT4 content of PM and purified TTs were seen in the absence of changes in the alpha 1-subunit of the Na(+)-K(+)-ATPase, a surface membrane marker.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446798 TI - Improved specificity of ICA assays in the Fourth International Immunology of Diabetes Serum Exchange Workshop. AB - The goal of the Fourth International Workshop for Standardization of ICA Measurements was to determine the specificity of ICA assays and their ability to distinguish between control sera (n = 57) and sera from IDDM-related individuals- representing relatives of IDDM patients (n = 21), healthy individuals who later developed IDDM (n = 8), or newly diagnosed IDDM patients (n = 23). Results from 28 laboratories were analyzed. The mean specificity (percentage of control sera reported as negative) among 27 laboratories was 91%, including 6 laboratories with 100% specificity. Nevertheless, 78% of laboratories found at least one control sample > 0 JDF U. Among samples from first-degree relatives, the mean concordance was 86%, including three sera found negative (0 JDF U) by all laboratories. Among individuals who later developed diabetes, the mean concordance was 93%, with two sera found positive by 100% of laboratories. In sera from newly diagnosed IDDM patients, the mean concordance was 82%. Three sera were found positive and one serum negative by all laboratories. The JDF U of the sera considered to be positive were significantly greater than each laboratory's average for the controls. In conclusion, the results from laboratories participating in the Fourth International ICA Workshop demonstrated excellent specificity, good concordance, and an ability to separate control sera from defined, IDDM-related subjects. PMID- 1446799 TI - The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents. AB - NIDDM patients with overt fasting hyperglycemia are characterized by multiple defects involving both insulin secretion and insulin action. At this point of the natural history of NIDDM, however, it is difficult to establish which defects are primary and which are acquired secondary to insulinopenia and chronic hyperglycemia. To address this question, we have studied the glucose-tolerant offspring (probands) of two Mexican-American NIDDM parents. Such individuals are at high risk for developing NIDDM later in life. The probands are characterized by hyperinsulinemia in the fasting state and in response to both oral and intravenous glucose. Insulin-mediated glucose disposal (insulin clamp technique), measured at two physiological levels of hyperinsulinemia (approximately 240 and 450 pM [approximately 40 and 75 microU/ml]), was reduced by 43 and 33%, respectively. During both the low- and high-dose insulin clamp steps, impaired nonoxidative glucose disposal, which primarily represents glycogen synthesis, was the major defect responsible for the insulin resistance. During the lower dose insulin clamp step only, a small decrease in glucose oxidation was observed. No defect in suppression of HGP by insulin was demonstrable. The ability of insulin to inhibit lipid oxidation (measured by indirect calorimetry) and plasma FFA concentration was impaired at both levels of hyperinsulinemia. These results indicate that the glucose-tolerant offspring of two NIDDM parents are characterized by hyperinsulinemia and manifest all of the metabolic abnormalities that characterize the fully established diabetic state, including insulin resistance, a major impairment in nonoxidative glucose disposal, a quantitatively less important defect in glucose oxidation, and a diminished insulin-mediated suppression of lipid oxidation and plasma FFA concentration. PMID- 1446800 TI - Glucose transporters of rat peripheral nerve. Differential expression of GLUT1 gene by Schwann cells and perineural cells in vivo and in vitro. AB - Expression of GLUTs in rat peripheral nerve was first studied at the mRNA level with Northern transfer analysis with cDNAs specific for GLUT1, GLUT2, GLUT3, and GLUT4. GLUT1 mRNA was the only GLUT mRNA detectable in rat sciatic nerve. In situ hybridization localized this mRNA to the perineurium and to some endo- and epineurial capillaries. Indirect immunofluorescence stainings demonstrated that GLUT1 protein epitopes were concentrated primarily in the perineurium and endoneurial capillaries. Also, some Schwann cells, a few epineurial capillaries, and medium-sized blood vessels showed a faintly positive immunoreaction. All cell types present in primary cultures initiated from rat sciatic nerve (perineurial cells, Schwann cells, and fibroblasts) expressed GLUT1 protein in vitro. Thus, Schwann cells, which expressed GLUT1 only occasionally at a low level in vivo, have the potential to express GLUT1 at a markedly higher level under cell culture conditions. Incubation of the cultures in 25 mM D-glucose for 7 days caused a 39% reduction in the amount of immunodetectable GLUT1 protein, and a marked (34%) decrease of GLUT1 mRNA compared with cultures incubated in 5.5 mM D-glucose. Interestingly, the reduction of [3H]-2-DG uptake in the same cultures exceeded 70%, suggesting that the reduced amount of GLUT1 protein alone did not explain the marked reduction in glucose uptake in these cultures. Immunostaining of the cell cultures suggested that perineurial cells were the main target for the glucose-induced decrease of GLUT1 protein. PMID- 1446801 TI - Intermittent hypoglycemia impairs glucose counterregulation. AB - IDDM patients who maintain strict glycemic control have impaired counterregulatory hormone and symptomatic responses to hypoglycemia. To test the hypothesis that intermittent exposure to hypoglycemia plays an etiological role in these defective responses, we produced 4 consecutive daily episodes of hypoglycemia in 10 healthy, nondiabetic volunteers by using the insulin clamp technique. Fasting (5.3 +/- 0.1 vs. 5.4 +/- 0.1 mM) and nadir (2.3 +/- 0.1 vs. 2.4 +/- 0.1 mM) glucose levels achieved during insulin infusion did not differ on study days 1 and 4. In contrast, the glucose levels required to stimulate an increase in EPI (2.8 vs. 3.1 mM), glucagon (2.8 vs. 3.2 mM), cortisol (2.4 vs. 2.9 mM), GH (2.6 vs. 3.0 mM), and autonomic hypoglycemic symptoms (2.2 vs. 2.5 mM) were all significantly lower on study day 4 versus study day 1 (P < 0.005 0.05). Basal levels of EPI and cortisol, but not glucagon, GH, or NE also were reduced on the final study day. We conclude that intermittent hypoglycemia can result in attenuation of the hormonal and symptomatic responses to insulin induced hypoglycemia and may contribute to the defective counterregulatory responses in patients with well-controlled IDDM. PMID- 1446802 TI - CD8 T cells are not required for islet destruction induced by a CD4+ islet specific T-cell clone. AB - A panel of CD4+ T-cell clones has been isolated from the spleen and lymph nodes of diabetic NOD mice. These clones have been shown to be islet-specific both in vivo and in vitro. One of the clones, BDC-6.9, initiates extensive damage to islet tissue when placed adjacent to an NOD islet graft that has been used to reverse diabetes in (CBA x NOD)F1 recipients or when injected intraperitoneally into such animals. In this study, we show that BDC-6.9 T cells can initiate islet destruction in the absence of detectable CD8 T cells either in the periphery or in the lesion that develops after the transfer of the cloned islet-reactive T cells. PMID- 1446803 TI - Polygenic nature of spontaneous diabetes in the rat. Permissive MHC haplotype and presence of the lymphopenic trait of the BB rat are not sufficient to produce susceptibility. AB - We describe the phenotypic characteristics of animals in the fifth backcross intercross generation of a breeding program in which the RT1 u haplotype and the phenotypic trait responsible for the T-lymphopenia of BB rats have been transferred to the ACI background. In this generation of animals, 24% were lymphopenic with decreased numbers of PBL expressing CD5, TCR alpha, and RT6. The PBL of the lymphopenic animals had a decreased mitogenic response to ConA. All of the nonlymphopenic animals were homozygous for RT6.2. Phenotypic analysis of intestinal IEL revealed that this was also the case for the lymphopenic animals. Moreover, IEL of the lymphopenic animals exhibited a pattern of staining (increased numbers of TCR alpha beta+CD4+CD8+ and decreased numbers of TCR alpha beta+CD4-CD8+) similar to that of BB DP animals. The ACI.1U(BB)-lymphopenic animals, although having two of the genetic traits associated with the expression of spontaneous diabetes mellitus, uniformly fail to develop diabetes. Breeding studies in which these animals were crossed with BB and hBB rats suggest that other genes are necessary for development of overt diabetes. PMID- 1446804 TI - Reevaluation of autoantibodies to islet cell membrane in IDDM. Failure to detect islet cell surface antibodies using human islet cells as substrate. AB - Since their demonstration in 1975, ICSAs have been proposed as serological markers and pathogenic elements in IDDM. ICSAs are detected in the sera of most newly diagnosed IDDM patients by indirect IFL that uses viable preparations of rat islet or insulinoma cells as substrate, but they also can be detected by using human insulinoma or fetal islet cells. We have tried to demonstrate ICSAs in the sera of 31 newly diagnosed diabetic patients, including 6 positive samples on human fetal islet cells, which used their natural target for the first time: normal human islet cells. In spite of using different types of preparations of these cells (i.e., freshly dispersed cell suspensions, monolayer cultures, or dispersed islets after culture), ICSAs could not be detected by IFL under the UV microscope, nor by flow cytometry. In contrast, 9 of 29 of the sera gave a positive staining on the RIN rat insulinoma cells. In an attempt to establish whether the putative ICSA autoantigen is present in the surface of human islet cells in the diabetic pancreas, the insulitis microenvironment was emulated by exposing the islets to three types of stress: 1) cytokines (IFN-gamma and TNF alpha); 2) heat shock; and 3) hyperglycemia. However, diabetic sera failed again to recognize membrane antigens on the islet cells after either of these treatments. Neither were islet cells from a newly diagnosed diabetic patient stained by its autologous serum (ICA titer > 80 JDF U). These results suggest that ICSA autoantigen is not expressed in the membrane of human islet cells and therefore raises doubts about their proposed pathogenic role. PMID- 1446805 TI - Sib-pair analysis of adenosine deaminase locus in NIDDM. AB - Recently, linkage between the ADA gene locus and MODY, a subtype of NIDDM, has been reported. The possibility that the region of chromosome 20q containing the ADA locus also may play a role in susceptibility to NIDDM needs to be investigated. Therefore, we examined the linkage between the ADA locus and NIDDM in affected siblings of 50 European white diabetic pedigrees--21 Italian and 29 British. Departure from independent segregation of the disease and an Alu VpA polymorphism within the 5' flanking region of the ADA locus was tested in the affected sib-pairs with the APM statistical method. After DNA amplification by the PCR and PAGE, five alleles were identified in the ALU VpA tract at the ADA locus in the two populations. Allele frequencies did not differ significantly between the two populations (chi 2 = 2.426, P > 0.05 [NS]). Analysis of the 50 diabetic sib sets, and independently of the Italian and British groups of affected sib pairs, revealed no segregation distortion between the marker locus and NIDDM. We conclude that mutations within or around the ADA locus are unlikely to play a major role in the etiology of NIDDM. PMID- 1446806 TI - PGE2 prevents anomalies induced by hyperglycemia or diabetic serum in mouse embryos. AB - Both a high level of D-glucose in the medium and serum from a diabetic rat can induce neural-tube fusion defects and growth retardation in cultured mouse and rat embryos. To test our hypothesis that a deficiency of PGs may be involved in the mechanism of hyperglycemia- and diabetic serum-induced teratogenesis and growth retardation, we added PGE2 to the medium of a whole mouse embryo culture containing either normal rat serum and 52.7 mM D-glucose (hyperglycemic) or diabetic rat serum and 22.2 mM D-glucose (diabetic). After a 24-h culture, 94% of hyperglycemic embryos and 81% of diabetic embryos had neural-tube fusion defects; in addition, the number of somites, the morphological score, and the protein content of the embryos were significantly lower than those of controls. Supplementing the medium with PGE2 at concentrations of 0.028-28.4 nM (hyperglycemic) or 28.4 nM (diabetic) significantly reduced the incidence of neural-tube defects and increased the number of somites, the morphological score, and the protein content. These results strongly support the hypothesis that the teratogenicity of diabetic serum, as well as the teratogenic action of hyperglycemic culture, are mediated through a deficiency of PGs. PMID- 1446807 TI - Longitudinal study of plasma lipoproteins and hormones during pregnancy in normal and diabetic women. AB - Plasma lipoproteins were studied longitudinally at the 1st, 2nd, and 3rd trimester of gestation and at postpartum and postlactation in 12 age-matched PGDM women, 9 GDM women, and 12 healthy control subjects. FPG and HbA1c were higher in every case in PGDM women than in control subjects, whereas in GDM patients, glucose was augmented only after parturition. FFA and beta-hydroxybutyrate levels were higher in both PGDM and GDM patients than in control subjects during gestation but not after parturition. Total TGs and VLDL, LDL, and HDL TGs increased with gestational time in the three groups and declined at postpartum, and although total cholesterol and VLDL, LDL, and HDL cholesterol followed a similar trend, their rise was less pronounced, and the decline after parturition was slower than that of the TGs in the three groups, with no difference among them. The VLDL TG/cholesterol ratio declined in the three groups at the 3rd gestational trimester, whereas in both LDL and HDL, the TG/cholesterol ratio, but not the cholesterol/phospholipid ratio, increased during gestation in the three groups, indicating a specific enrichment of TGs in these particles. The increase in apoA-I and apoB with gestation was parallel to the respective changes in HDL and LDL cholesterol and, again, no difference was observed between the three groups. Plasma levels of beta-estradiol, progesterone, and prolactin increased sharply with gestation and declined at postpartum in the three groups, but absolute values of beta-estradiol and prolactin, at the three trimesters of gestation, were lower in PGDM patients, but progesterone levels were lower than controls in GDM women only at the 3rd trimester. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446808 TI - Intrathymic islet cell transplantation reduces beta-cell autoimmunity and prevents diabetes in NOD/Lt mice. AB - Intrathymic transplantation of syngeneic islets into adolescent NOD/Lt mice was performed to establish whether the thymus would serve as an immunoprivileged site for beta-cell engraftment, and whether this treatment would prevent the development of diabetes by eliciting tolerance to islet antigens. Intrathymic injection of cells from 200 NOD islets into 4-wk-old female NOD/Lt mice produced a significant reduction in the severity of insulitis at 24 wk of age. Furthermore, diabetes development was strongly suppressed (11% incidence) compared with controls (100% incidence). Both thymus histology and thymic insulin content revealed a rapid loss of the implanted beta-cells with < 1% remaining 1 wk posttransplantation. Despite the rapid loss of thymus-implanted islet cells, evidence for tolerance induction to islet cell antigens was obtained by adoptive transfer of splenic leukocytes from these mice into NOD-scid/scid recipients. After adoptive transfer of splenic leukocytes from 24-wk-old untreated prediabetic donors, 4 of 5 NOD-scid/scid recipients developed diabetes within 4 wk, and none of the recipients became diabetic after transfer of splenocytes from intrathymic islet-implanted donors. Intrathymic islet transplantation did not lead to reduction of sialitis in females with reduced severity of insulitis, indicating that the protective effect was tissue specific. This also was reflected in adoptive transfer experiments, because equal severity of sialitis was observed in NOD-scid/scid recipients of spleen cells from either islet transplanted or control NOD/Lt mice. In conclusion, the data suggest that intrathymic injection of islet cells prevents diabetes by stimulating immunological tolerance to beta-cells. PMID- 1446809 TI - [Immunogenetics of immunoglobulins in domestic mink. VII. Features of phenotypic expression of gamma-heavy chain constant region allotypes mask linkage of IgCH genes]. AB - Reduced expressivity and penetrance of allotypes H2-H4 and the regulation of allotype H6 expression by regulatory gene concealed the linkage of mink C genes in statistical analyses. Their linkage was demonstrated by di- and polyhybrid test crosses with 3, 4 and more generations. PMID- 1446810 TI - [Variability of polymorphic gene markers in Buryat and Russian newborns from Ulan Ude]. AB - Variability of ten polymorphic loci (ABO, RhD, PGD, ACP, PGM1, GLO, ESD, ADA, GC, TF) was studied in 326 Buryat and 310 Russian newborns from Ulan-Ude city. Marked differences between two groups were observed in the distributions of allelic frequencies of ABO, RhD, PGD, ACP, PGM1, GLO, ESD, GC loci. Genetic similarities between Buryat and other mongoloids were estimated. Close similarity was observed between Buryat, Mongols, Yakut and Kyzyl. PMID- 1446811 TI - [Distribution of abnormal hemoglobins S and C in the Republic of Guinea]. AB - Distribution of the HbS and HbC in the Guinean Republic was determined by the analysis of the excerption of 2213 inhabitants representing different ethnic groups of the country. It was found that the mean frequency of the HbS heterozygotes is 21.2 +/- 0.9% and of the HbC heterozygotes is 2.6 +/- 0.3%. Among major nationalities of the country the frequencies of the HbS heterozygotes make up 21.0 +/- 1.9% for the Fulbe, 22.2 +/- 1.6% for the Malinke and 26.5 +/- 1.6% for the Susu and frequencies of the HbC heterozygotes make up 3.0 +/- 0.8% for the Fulbe, 2.5 +/- 0.6% for the Malinke and 1.6 +/- 0.4% for the Susu. Relative viability of the HbS and HbC carriers for major Guinean nationalities is estimated. The relative fitnesses account is 1.05-1.13 for HbC heterozygotes and 1.07-1.16 for HbC heterozygotes. PMID- 1446812 TI - [A line of Chinese hamster cells containing human chromosome 18]. PMID- 1446813 TI - [Role of activated cellular c-Ha-ras-1 oncogene in the mutagenic effect of the plasmid pEJ6.6]. AB - The role of the activated oncogene c-Ha-ras-1 from human bladder carcinoma integrated into the pEJ6.6 plasmid in the mutagenic effect of the plasmid was studied in Chinese hamster cells. The frequency of hypoxanthine phosphoribosyltransferase defective (HPRT-) mutants after treatment with pEJ6.6 containing an active c-Ha-ras-1 exceeded that in control dishes treated with a derivative of pEJ6.6 plasmid with an inactivated oncogene. The inactivation was achieved by introducing a deletion into the coding region of the oncogene. The mutagenic effect was rather weak but statistically significant. Thus, the data obtained show that the mutagenic activity of pEJ6.6 plasmid is determined by its oncogene. The role of mutagenic effects of activated cellular oncogenes in malignant transformation is discussed. PMID- 1446814 TI - [Dependence of mutagenic activity of heterocyclic analogs of pyrene on their chemical structure]. AB - Comparative mutagenic activity of 6 heterocyclic analogs of pyrene was studied. The highest activity was revealed for 2,7-dinitro-4,9-dioxy-5,10-dioxo-4,5,9,10 tetrahydro-4,9- diazapyrene (2,7-DN-DDTDP) and 2,7-dinitro-5,10-dioxo-4,9 dioxapyrene (2,7-DN-DDP) which induced mutations in the tester strain Salmonella typhimurium TA98 and TA100. High mutagenicity of 2,7-DN-DDTDP and 2,7-DN-DDP is conditioned by reduction of nitro groups in the 2,7 position. The carbonyl groups in the 5,10 position were believed to cause bifunctional activity of 2,7-DN-DDTDP and 2,7-DN-DDP and to promote deletion of two G-C in the D3052 site. PMID- 1446815 TI - [Activity of nucleolus organizer regions (NORs) in embryonic livers from twin minks]. AB - Ag-NOR patterns were studied in hepatocytes from nine mink embryo siblings, including a pair of monochorionic (presumably monozygotic, MZ) twins. Both the number and the size of Ag-NORs per cell were found to be identical in MZ twins. All the other sibs had the patterns different from each other and from the MZ ones. The conclusion is that the NORs activity is a strongly inherited character and the Ag-NOR pattern can be used as a reliable genetic marker to distinguish the twin zygosity. PMID- 1446816 TI - [Influence of mutations in the suppressor of hairy wing and modifier of MDG4 loci on phenotype expression of super-unstable alleles at the yellow locus of Drosophila melanogaster]. AB - A number of super-unstable systems were obtained earlier by the induction of P-M hybrid dysgenesis in the strains with a mobilized Stalker. One of the super unstable mutations appeared at the yellow locus of Drosophila melanogaster on the background of preexisting y mutation. The latter had been induced by mdg4 insertion into the regulatory region of the yellow locus. The suppressor genes of Hairy wing and modifier of mdg4 are known to encode proteins which bind to the mdg4 enhancer and are involved in the control of its transcription. A large spectrum of yellow alleles was obtained in super-unstable systems which could be recognized by the intensity of pigmentation in twelve different areas of the cuticle. Combining of these alleles with su(Hw) and mod(mdg4) mutations followed by the study of phenotype changes demonstrated that the same regulatory protein may influence expression of the gene in opposite directions. PMID- 1446817 TI - [Modification of drug mutagenicity by their immobilization. Effect of prostatilen immobilized in polyvinyl alcohol in mice]. AB - Mutagenic drug effect of prostatilen and the possibility of modification were analysed in the sperm head anomalies (SHA) and the bone marrow cell aberrations (CA) tests in Mus musculus. It was found that intraperitoneal injection of 2.5 micrograms of prostatilen induced no significant increase in SHA and CA frequencies, the dose of 5 micrograms inducing both SHA and CA. Ultrafiltration of prostatilen led to decrease in its mutagenicity in the SHA test. Immobilization of the drug (5 and 10 micrograms) in polyvinyl alcohol reduced SHA and CA frequencies, the former decreasing to the control level. PMID- 1446818 TI - Construction and characterisation of a yeast artificial chromosome library containing two haploid Beta vulgaris L. genome equivalents. AB - We have constructed a yeast artificial chromosome (YAC) library using high molecular-weight DNA prepared from agarose-embedded protoplasts of a sugar beet (Beta vulgaris L.) cell suspension line, Ar+. This library contains 15,000 clones with an average insert size of 140 kb. Based on a sugar beet haploid genome size of 1.1 x 10(3) Mb it should represent approximately two haploid genome equivalents. The library is organised as an ordered array in duplicate microtitre plates. High-density filters, each containing 864 YAC clones, have been screened in colony hybridisation experiments. In this way, sugar beet YAC clones have been identified containing chloroplast DNA, mitochondrial DNA and two satellite DNAs. Ten pools of DNA from 1500 individual YAC clones have also been prepared for rapid PCR screening of the library. Using this approach, in combination with colony hybridisation, we have been able to isolate sugar beet YAC clones containing a transcribed low-copy-number gene. PMID- 1446819 TI - Trans-splicing of an early embryo mRNA in Litomosoides carinii, coding for the major microfilarial sheath protein gp22. AB - Both genomic and cDNA clones have been isolated encoding the major sheath glycoprotein, gp22, of Litomosoides carinii microfilariae. The mature gp22 mRNA is shown to result from both trans-splicing of a 22-nucleotide 5'-leader sequence to an acceptor site at position 313 of the pre-mRNA, immediately upstream from the start codon, and from cis-splicing of a 117-nt intron located within the coding sequence. Cis-splicing precedes the trans-splicing reaction. The gp22 reading frame of 148 codons has the inferred structure of a prepro-protein and includes a leader peptide and a pro-segment ahead of the known N terminus of the mature, extracellular protein of 105 amino acids. The N-terminal part of that protein contains five repeats of an elastin-related pentapeptide sequence, which, together with a proline-threonine segment between two Cys clusters in the center and at its C terminus, may cause an elongated conformation with an apparent molecular size of 22 kDa in contrast to the calculated M(r) of 11,200. PMID- 1446820 TI - Conservation of gene organization and trans-splicing in the glyceraldehyde-3 phosphate dehydrogenase-encoding genes of Caenorhabditis briggsae. AB - The genes encoding body-wall-specific glyceraldehyde-3-phosphate dehydrogenase from Caenorhabditis briggsae were sequenced and compared to the homologous genes from Caenorhabditis elegans. The direct tandem organization of these genes, gpd-2 and gpd-3, and the size and location of the two introns in each gene are the same in C. elegans and C. briggsae. Primer-extension studies demonstrated that the two genes in C. briggsae are trans-splice differentially with the same splice leader (SL) RNAs as are observed in C. elegans. The gdp-2 gene is trans-spliced with SL1 while gdp-3 is trans-spliced with SL2. Significant sequence conservation was observed within the promoter regions of each species and may indicate those regions responsible for body-wall-muscle-specific gene expression and/or differential trans-splicing. Comparisons of the sequences suggest that the tandem repeat of the genes has been subjected to concerted evolution and that C. briggsae and C. elegans diverged much earlier than would be anticipated based on morphological similarities alone. Finally, an open reading frame found several hundred nucleotides upstream from gpd-2, in both species, appears to be homologous to the ATP synthase subunit, ATPase inhibitor protein, from bovine mitochondria. PMID- 1446821 TI - Regulatory elements and transcriptional regulation by testosterone and retinoic acid of the rat nerve growth factor receptor promoter. AB - The low-affinity nerve growth factor receptor (LNGFR) is a membrane-associated glycoprotein which is thought to participate in some of the biological activities of nerve growth factor (NGF). Expression of the LNGFR gene is known to be regulated both during development and in response to various agents in cell culture. However, molecular mechanisms responsible for the regulation have not been described. We report here an analysis of a 4.8-kb sequence from the 5' flanking region of the rat LNGFR gene. Several regulatory elements were identified in this region by transfection of plasmid constructs containing sequences from LNGFR fused to a bacterial cat reporter gene. The proximal part of the promoter region (0.4-kb) was shown to be sufficient to support cat expression in all cell types used. A silencer element located between -1.5 kb and -1.8 kb from the start of translation, as well as an enhancer element in more upstream regions of the promoter, were identified in the phaeochromocytoma cell line, PC12, and in the Sertoli cell line, TM4, that express the LNGFR gene. Treatment of TM4 cells with retinoic acid (RA) increases the level of LNGFR mRNA twofold, while testosterone treatment results in a tenfold decrease. Regions of the promoter responsive to testosterone and RA in TM4 cells were found at -610 to 860 bp and -1840 to -4800 bp upstream from the translation start codon, respectively. A RA-responsive element active in PC12 cells is located between bp 610 to -860 from the start codon. PMID- 1446822 TI - Cloning of the goat beta-casein-encoding gene and expression in transgenic mice. AB - The goat beta-casein-encoding gene (CSN2), which encodes the most abundant protein of goat milk, has been cloned and sequenced. The intron/exon organization of the 9.0-kb goat CSN2 gene is similar to that of other CSN2 genes. Expression of the goat gene was principally restricted to the mammary gland of lactating transgenic animals. A low level of expression was also observed in skeletal muscle and skin. In contrast to a rat CSN2 transgene [Lee et al., Nucleic Acids Res. 16 (1988) 1027-1041], the goat gene was expressed to a high degree in the lactating mammary gland. Differences in the content or context of regulatory elements may account for the enhanced performance of the goat relative to the rat CSN2 gene in transgenic mice. PMID- 1446823 TI - Transgenic pigs carrying cDNA copies encoding the murine Mx1 protein which confers resistance to influenza virus infection. AB - An important aspect of gene transfer into farm animals is the improvement of disease resistance. The mouse Mx1 protein is known to be sufficient to confer resistance to influenza viruses. Gene constructs containing the mouse Mx1 cDNA controlled by the human metallothionein IIA promoter (hMTIIA::Mx), the SV40 early enhancer/promoter region (SV40::Mx) and the mouse Mx1 promoter (mMx::Mx) were transferred into pigs. The results of the gene transfer experiments with the hMTIIA::Mx and the SV40::Mx constructs indicate that the permanent high-level synthesis of Mx1 might be deleterious to the organism: the gene transfer efficiency was surprisingly low, and all transgenic piglets born had rearrangements in their transgene copies that abolished protein synthesis. The use of the interferon (IFN)- and virus-inducible mMx::Mx construct resulted in normal gene transfer efficiency. Two transgenic pig lines could be established which expressed IFN-inducible mouse Mx1 mRNA. Extensive protein analysis did not detect mouse Mx1 in IFN-treated transgenic animals. PMID- 1446824 TI - Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the alpha-chain of the human interleukin-2 receptor. AB - The general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the alpha-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2R alpha chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy. PMID- 1446825 TI - Intrahelical pseudoknots and interhelical associations mediated by mispaired human minisatellite DNA sequences in vitro. AB - The human minisatellite arrays, 33.6 and 33.15, consist of tandem reiterations of a 37-nucleotide (nt) and a 16-nt repeat unit sequence, respectively, both of which contain a majority of purine bases on one strand. Knot-like tertiary structures, which mapped to the cloned arrays, were observed by electron microscopy (EM) in homoduplex molecules produced by denaturation and reannealing in vitro. They result from a primary hybridization between misaligned repeat units of the array, forming a slipped-strand structure with staggered single stranded DNA loops, followed by a secondary hybridization between repeat units in the two loops. Depending on the relative alignment of the loops when they hybridize, a particular form of intrahelical pseudoknot is produced. Theta shaped, figure-of-eight, and bow-shaped structures were the most common conformational isomers observed in homoduplexes flattened into two dimensions during EM preparation. At the site of a bow-shaped structure, a conformation dependent bend of approximately 60 degrees between the flanking DNA segments is induced; the other conformations generally do not deflect the line of the main DNA axis. Paired loops, similar to the bow-shaped structure, were apically situated in some supercoiled plasmids containing the 33.6 array. Both plasmids formed intermolecular associations, consisting of two (or more) homoduplex molecules held together at or immediately adjacent to a nexus which mapped to the minisatellite sequences. These associations might arise either by interhelical hybridization between arrays or by knot-like structures interfering with branch migration of chi-form Holliday junctions. PMID- 1446826 TI - A human endogenous long terminal repeat provides a polyadenylation signal to a novel, alternatively spliced transcript in normal placenta. AB - We have been investigating the impact that the long terminal repeats (LTRs) of the RTVL-H family of human endogenous retroviral-like elements may have on the expression of adjacent cellular genes. Using a differential hybridization strategy, we have screened a cDNA library from a normal full-term human placenta and have identified two clones containing non-RTVL-H-related cellular sequences that have been polyadenylated within an RTVL-H LTR. One of these clones, cPj-LTR, contains an open reading frame (ORF) of 223 amino acids. Southern analysis indicated that the corresponding gene, termed PLT, is most probably a single multi-exon locus and that related sequences are present in the mouse genome, suggesting that this gene has been evolutionarily conserved. Database searches detected no significant homology to previously published sequences, indicating that PLT is a novel gene. Northern analysis identified several PLT-related transcripts in placental RNA samples, one of which is associated with the LTR. The presence of this PLT-LTR fusion transcript in normal placenta was also confirmed by PCR. Additional hybridization studies with RNAs from various cell lines suggested that the PLT locus is differentially expressed in different cell types. To investigate the structure of the non-LTR-associated PLT-related transcripts, additional clones were isolated from the placental cDNA library. Analysis of these clones suggests that the PLT mRNA undergoes alternative splicing at its 3' end, with polyadenylation within an RTVL-H LTR occurring in one of the resulting transcripts. PMID- 1446827 TI - Production and secretion of high levels of recombinant human acetylcholinesterase in cultured cell lines: microheterogeneity of the catalytic subunit. AB - To allow for structural analysis of the human acetylcholinesterase (hAChE) subunit, a series of eukaryotic vectors was designed for efficient expression. Several eukaryotic multicistronic expression vectors were tested in various mammalian cell lines. All expression vectors contained the selectable neo gene under control of a weak promoter, while the hAChE cDNA was under control of the cytomegalovirus (CMV) immediate-early or Rous sarcoma virus long terminal repeat (RSV LTR) or simian virus 40 (SV40) early promoters. Optimal production and secretion of recombinant hAChE (rehAChE) was achieved in the embryonal kidney 293 cell line transfected either with the RSV-hAChE or with CMV-hAChE expression vectors. Clones expressing and secreting as much as 5-25 pg of enzyme per cell per 24 h were obtained without resorting to coamplification techniques or continuous maintenance of cells under selective pressure. The purified (specific activity of 6000 units per mg protein) homodimer and tetramer enzyme molecules displayed typical AChE biochemical properties: a Km value of 120 microM for acetylthiocholine; a kcat value of 3.9 x 10(5)/min, and selective by AChE specific inhibitors. Catalytic subunit dimers (130 kDa) exhibit differential N glycosylation patterns, and upon reduction resolve into 67- and 70-kDa monomeric subunits. These two forms appear as a single discrete 62-kDa band following deglycosylation by N-glycanase. The N-terminal amino acid sequence analysis of the purified mature enzyme suggests the existence of two alternative cleavage sites for the removal of the signal peptide, in which the 'mature' position 1 is either Ala31 or Gly33. Both of these positions conform with the consensus signal peptide recognition sequences and demonstrate bidirected processing of signal peptides on a native molecule. PMID- 1446828 TI - Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase. AB - Human chi-alcohol dehydrogenase (chi-ADH) is a zinc-containing dimeric enzyme responsible for the oxidation of long-chain alcohols and omega-hydroxyfatty acids. Class-III ADHs, of which chi-ADH is the prototype, are widely produced and well conserved during evolution. This suggests that they fulfill important housekeeping roles in cellular metabolism. Recent evidence suggests that class III ADH and formaldehyde dehydrogenase (FDH) are the same enzyme. We have isolated and characterized two overlapping genomic clones that cover the entire ADH5 (FDH) gene. ADH5 is composed of nine exons and eight introns. Two major transcription start points were identified by primer extension. The 5' nontranslated region is unusual in that it contains two additional upstream ATG codons, which would encode peptides of 20 and 10 amino acids. Neither of the upstream ATGs is in a good context for translation initiation, whereas the ATG initiating &khgr;-ADH is in a favorable context. The 5' region of ADH5 is a CpG island; it is extremely G+C rich and has many CpG doublets. It does not contain either a TATA box or a CAAT box. This is consistent with ubiquitous expression, and contrasts with the promoters of all previously cloned ADH genes, which are expressed in a tissue-specific manner. The 5' region of ADH5 contains consensus binding sites for the transcriptional regulatory proteins, Sp1, AP2, LF-A1, NF-1, NF-A2, and NF-E1. A 1.5-kb upstream fragment from ADH5 was able to drive the transcription of a cat reporter gene at high levels in monkey kidney cells (CV 1). Several processed pseudogenes were also isolated. PMID- 1446829 TI - Expression of the human ADH2 gene: an unusual Sp1-binding site in the promoter of a gene expressed at high levels in liver. AB - The sequence 5'-GTGGGTGTGGC (G3T) is important for the efficient initiation of transcription from the human ADH2 promoter. We show here that the purified transcription factor Sp1 binds with high affinity to the G3T site of ADH2 (encoding beta beta-alcohol dehydrogenase), even though the G3T sequence does not contain the canonical Sp1-binding site, GGGCGG. Proteins from mouse liver nuclei and purified Sp1 both footprint the same sequence of the ADH2 promoter with similar patterns. UV crosslinking demonstrates that the major G3T-binding protein in the liver extract is similar in size to Sp1. Mouse liver nuclear extract resembles purified Sp1 in its relative binding affinity to a series of oligodeoxyribonucleotides containing either the Sp1-binding site or variants of the G3T sequence. These data indicate that the G3T sequence can interact with Sp1 and that Sp1 may be important in the expression of ADH2. The G3T sequence from the closely related ADH3 gene (encoding gamma gamma-alcohol dehydrogenase) differs from that of ADH2 in the first two nucleotides; it binds both the liver protein and purified Sp1 with lower affinity. This might explain why ADH3 is expressed at lower levels than ADH2 in the liver. PMID- 1446830 TI - Affinity purification of histidine-tagged proteins transiently produced in HeLa cells. AB - In order to produce eukaryotic proteins in a functional state, it is often necessary to use eukaryotic instead of prokaryotic expression systems. We have designed vectors which can be employed to express either N- or C-terminally histidine-tagged proteins in transiently transfected eukaryotic cells. The histidine tag allows the rapid enrichment of these proteins by metal chelate affinity chromatography in a native and functional state. Yields of up to 5 micrograms protein/5 x 10(7) cells were achieved. PMID- 1446831 TI - Characterization of a gene that encodes a homologue of protein kinase in Arabidopsis thaliana. AB - Cloning and analysis of a gene that encodes a homologue of protein kinase (PK) from Arabidopsis thaliana is reported. Oligodeoxyribonucleotides (oligos) corresponding to conserved regions in catalytic domains of various PKs were used for polymerase chain reaction (PCR) amplification with genomic DNA from A. thaliana as template, in an attempt to identify genes encoding PK in plants. We obtained several amplified DNA fragments that encoded part of a PK. We screened a genomic DNA library of A. thaliana with these oligos or PCR fragments as probes. Three genomic clones were obtained and one of them, named Atpk7, was sequenced and analyzed. Atpk7 was demonstrated by PCR to contain an intron. The mRNA transcribed from Atpk7 was detected predominantly in root tissue by Northern blot analysis. The transcription start point was determined by primer extension. The deduced amino acid (aa) sequence of the putative product of Atpk7 resembles those of S6 kinases, cyclic nucleotide-dependent PKs and calcium-dependent PKs. From this comparison of aa sequences, the ATPK7 protein is considered to be a member of a novel subfamily of Ser/Thr PKs in plants. PMID- 1446832 TI - Cloning and characterization of cDNAs coding for heavy and light chains of a monoclonal antibody specific for pre-S2 antigen of hepatitis B virus. AB - Binding specificity of a monoclonal antibody (mAb) (kappa, gamma 2b) H8 which can react with the pre-S2 peptide of hepatitis B virus (HBV) was determined by Western blot analyses. From the hybridoma cell line secreting mAb H8, poly(A)+ RNA was prepared and used as a template for cDNA synthesis and cloning. Full length cDNAs coding for the heavy and kappa light chains of the mAb were cloned from the cDNA library and characterized by nucleotide (nt) sequence analyses and N-terminal amino acid sequencing. The sequence analyses revealed that both heavy and light chain-specific cDNAs are functional, and the variable regions of the heavy and light chains are members of mouse heavy chain subgroup III(c) and light chain group I, respectively. Comparison of the nt sequences with mouse immunoglobulin genes listed in the GenBank data base show that the cDNAs have not been previously reported. The cDNAs will be used for the construction of a therapeutic antibody for HBV infection. PMID- 1446833 TI - Cloning and sequencing of the cDNA encoding tyrosinase of the Japanese pond frog, Rana nigromaculata. AB - We cloned and sequenced the cDNA encoding tyrosinase (TYN) of the Japanese pond frog, Rana nigromaculata. The 3511-bp cDNA contained a 54-bp 5'-noncoding region, a 1596-bp open reading frame encoding TYN of 532 amino acids (aa), and a 1861-bp 3'-noncoding region. The aa sequence of frog TYN predicted from the cDNA sequence was homologous to that of mouse and human TYNs. The aa sequence including the copper-binding domain, which is likely the active center of TYN, was highly conserved among these three species and Neurospora crassa, Streptomyces antibioticus, and S. glaucescens. The frog TYN also contains possible glycosylation sites and conserved Cys at sites similar to those in the mouse and human TYNs. There are two hydrophobic regions at the N-terminus and near the C terminus, which are likely the signal (leader) peptide and a transmembrane domain, respectively. PMID- 1446834 TI - The use of a wild-type dihydrofolate reductase-encoding cDNA as a dominant selectable marker and induction of expression by methotrexate. AB - The cDNA (DHFR) encoding the wild-type (wt) dihydrofolate reductase (DHFR) was used as a dominant selectable marker in the transfection of murine hybridoma Sp2/0-Ag14 cells by protoplast fusion. The initial clones contained 100-400 copies of integrated plasmid DNA, and the high level of wt DHFR protein produced enabled the cells to survive the drug selection at 100 nM methotrexate (MTX). The expression of the gene of interest was several fold higher than when the mutant DHFR with decreased MTX binding was used as the selection marker, presumably because the clones were more sensitive to the stress induced by MTX. When the clones were propagated at higher concentrations of MTX, expression of both DHFR and the gene of interest increased. This induction is freely reversible, and we have shown that it is controlled at the transcriptional level, by nuclear run-off transcription assays. PMID- 1446835 TI - A rat brain-derived neurotrophic factor-encoding gene generates multiple transcripts through alternative use of 5' exons and polyadenylation sites. AB - As a first step toward clarification of the transcriptional controls of the gene encoding brain-derived neurotrophic factor (BDNF), we cloned and sequenced a rat genomic DNA fragment carrying this gene. RNA blotting analysis using a probe derived from the 3'-flanking region of BDNF revealed that alternative use of 3' polyadenylation sites generates at least two BDNF transcripts that differ in the size of the 3'-noncoding region. Furthermore, sequence analysis of the 5'-end of the BDNF cDNA revealed the presence of at least six different types of transcripts which were probably derived through alternative use of the multiple 5'-exons. Therefore, a single BDNF gene could produce multiple types of transcripts with different noncoding sequences through alternative use of both 5' exons and 3'-transcription termination sites. PMID- 1446836 TI - The human ribosomal protein S6 gene: isolation, primary structure and location in chromosome 9. AB - Using PCR cloning we isolated the first intron of the human ribosomal protein S6 gene (hRPS6). By screening the human HeLa cell cDNA library in lambda ZAPII vector (Stratagene, La Jolla, CA), we identified and sequenced a partially spliced pre mRNA copy of hRPS6. The complete hRPS6 gene was isolated from a lambda DASH library with an intron-specific probe. The gene and flanking regions were sequenced, and the mRNA 5' end was mapped by primer extension experiments. The hRPS6 gene has 6 exons and 5 introns and is 3.6 kb long. Using intron specific primers in PCR and a panel of human-hamster cell lines we localized the hRPS6 gene in human chromosome 9. PMID- 1446837 TI - Cloning and sequencing of a human cDNA coding for dihydroorotate dehydrogenase by complementation of the corresponding yeast mutant. AB - Dihydroorotate dehydrogenase (DHOdehase, EC 1.3.3.1) catalyses the fourth enzymatic step in de novo pyrimidine biosynthesis. A truncated human cDNA encoding this enzyme was isolated from a HeLa cell cDNA library by functional complementation of a corresponding deletion mutant from the yeast, Saccharomyces cerevisiae. The complementing clone contained a 1.5-kb poly(A)(+)-tailed insert with a 1191-bp open reading frame, hybridising with a unique human mRNA of 1.6 kb. The deduced amino acid sequence has 54%, 46% and 42% identity with Arabidopsis thaliana, Schizosaccharomyces pombe and Escherichia coli DHOdehases, respectively. In contrast, it has only 21% identity with the S. cerevisiae enzyme, which probably reflects the cytosolic location of the enzyme in the latter organism. PMID- 1446838 TI - Cloning and sequencing of a jack bean urease-encoding cDNA. PMID- 1446839 TI - HMOs: 'medicine, Soviet style'? PMID- 1446840 TI - FDA user fee may speed approval of Alzheimer's, Parkinson's drugs. PMID- 1446841 TI - Diagnostic clues can help identify patients with renal artery stenosis. PMID- 1446842 TI - COPD: primary care management with drug and oxygen therapies. AB - Chronic obstructive pulmonary disease related in most cases to extensive cigarette smoking is a leading cause of morbidity and mortality among patients age 55 and older. Smoking cessation, inhaled anticholinergic therapy, and oxygen supplementation (when indicated) are primary treatment modalities. Nicotine administration via a transdermal system or polacrilex is the pharmacologic method of choice for smoking cessation. Concomitant group psychotherapy increases the likelihood of success. Beta agonists, mucolytics, and antibiotics can be useful in selected subgroups. Steroids and theophylline are controversial in COPD and should be used with caution. Prognostic indicators, such as degree of reversible airway disease, aid in long-term care decisions. PMID- 1446843 TI - Controversies in the management of cerebrovascular disease in older patients. AB - Several ongoing studies are evaluating the optimal management of patients with cerebrovascular disease. The Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin (CASANOVA) study has shown that carotid endarterectomy is not recommended for asymptomatic patients with less than 90% carotid stenosis. The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgical Trial (ECST) have demonstrated that endarterectomy should be considered for patients who had recent carotid artery territory ischemic symptoms associated with angiographically defined stenosis of greater than 70%. These and other trials are expected to provide further data regarding management of cerebrovascular disease, including treatment of those patients with moderate (30 to 69%) carotid stenosis. Until that time, treatment decisions must be made on a case-to-case basis. PMID- 1446844 TI - Healthier lifestyles: how to motivate older patients to change. AB - A 1- to 3-minute clear discussion by the family physician of the risks of unhealthy lifestyles has been found to be quite successful in countering patients' denial of personal risk. Studies indicate that the physician's authority lends credibility to the need to make a change and is a strong motivator. An office-based physician counseling model has proven effective in motivating older patients to adopt healthier lifestyles. The model includes four basic steps: patient assessment, discussion of risk and delivery of a message to change, a prescription for change (planning and carrying out of a behavior change strategy), and prevention of relapse through a maintenance program. PMID- 1446845 TI - Clinton and healthcare reform: what to watch for in the first 100 days. PMID- 1446846 TI - Extracellular-superoxide dismutase type C (EC-SOD C) reduces myocardial damage in rats subjected to coronary occlusion and 24 hours of reperfusion. AB - Extracellular-superoxide dismutase type C (EC-SOD C) is a secretory SOD isoenzyme which, in contrast to the intracellular CuZn SOD, has affinity to the endothelium and a long vascular half-life. In the present study, the effects of EC-SOD C and CuZn SOD on reperfusion-induced myocardial damage were determined in rats subjected to 10 min of left coronary artery ligation followed by 24 h of reperfusion. Recombinant human EC-SOD C (rh-EC-SOD C) or the corresponding volume of the vehicle was administered after completion of the coronary ligation. CuZn SOD was given in two equal doses, the first dose directly after ligation and the second one 6 h later. At the end of the reperfusion period the myocardial damage was quantified by measuring the creatine kinase concentration (CK) in the reperfused part of the left ventricular free wall (LVFW), and expressed as a percentage of the concentration in the non-ischemic septum. In the group given the vehicle, 47 +/- 10 (mean +/- SD) of the CK remained in the reperfused LVFW. In the rats receiving rh-EC-SOD C the corresponding values for each dose: 1.4, 4.2 and 12.6 mg/kg were 55 +/- 12 (ns), 55 +/- 12 (ns) and 65 +/- 12% (p less than 0.05, vs. vehicle, Dunnett's multiple comparison test), respectively. Administration of CuZn SOD (2 x 10 mg/kg) resulted in 58 +/- 16% (ns) CK remaining in the LVFW.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446847 TI - Thioctic acid protects against ischemia-reperfusion injury in the isolated perfused Langendorff heart. AB - Antioxidant properties of thioctic and dihydrolipoic acid have been demonstrated in membranes and low density lipoproteins (LDL) in vitro. In vivo studies with dietary supplementation of thioctic acid to rats showed that it can also protect tissues against oxidative damage. Presumably, this action is due to a thioctic acid dihydrolipoic acid (TA/DHLA) coupled antioxidant mechanism, which enhances the activity of other antioxidants (i.e. ascorbate, alpha-tocopherol) by regenerating them from their radical form. In the present study, thioctic acid proved to protect against ischemia/reperfusion injury to Langendorff perfused hearts. Hearts isolated from rats fed thioctic acid and subjected to ischemia exhibited better mechanical recovery (left ventricular developed pressure) after reperfusion and lower lactate dehydrogenase leakage. Thioctic acid supplementation also decreased the appearance of fluorescent lipid peroxidation products after ischemia/reperfusion, lowered the rate of 2,2'-azobis-(2,4 dimethylvaleronitrile) (AMVN) induced lipid peroxidation in heart homogenates, and prevented the loss of alpha-tocopherol. The total sulfhydryl group content in thioctic acid fed animals was higher and the decrease due to ischemia-reperfusion was not as marked in this group as observed in the control. These results show that dietary supplementation with thioctic acid in vivo provides protection against ischemia/reperfusion injury in the Langendorff heart model. PMID- 1446848 TI - New forms of treatment for inflammatory bowel disease. PMID- 1446849 TI - Trophic effect of gastrin on the enterochromaffin like cells of the rat stomach: establishment of a dose response relationship. AB - Gastrin was given to rats by continuous subcutaneous infusion through implanted osmotic minipumps in doses covering a wide range of the dose response relationship for gastrin with regard to the trophic effect on the enterochromaffin like cells of the oxyntic mucosa. Thirty five rats were divided into five groups (each of seven rats), one group receiving a control solution of 1% albumin, the others receiving gastrin in 1% albumin at doses of 2.5, 5, 10, and 15 micrograms/kg/h, respectively. The plasma gastrin concentrations in the various groups increased in the same order of magnitude as expected from the gastrin doses given. Gastrin induced a dose dependent increase in enterochromaffin like cell density, oxyntic mucosal histamine concentration and histidine decarboxylase activity up to the dose of 5 micrograms/kg/h, where the increase levelled off. Hence, the dose response relationship for the trophic effect of gastrin on the enterochromaffin like cells seems to follow a polynomial rather than a linear function. These findings may also contribute to the understanding of the trophic effect of gastrin on enterochromaffin like cells in man with conditions associated with hypergastrinaemia. PMID- 1446850 TI - Gastric B-cell mucosa associated lymphoid tissue lymphoma: a clinicopathological study in 56 patients. AB - Clinico-pathological features of 56 patients with primary gastric lymphoma were evaluated retrospectively. All cases were regraded according to a classification of Isaacson et al into high grade and low grade B-cell mucosa associated lymphoid tissue lymphoma. A third group of mixed grade was recognised in 11 patients with low grade who also had occasional areas of high grade. Low grade and mixed grade patients had a 100% actuarial survival at 156 months, which was significantly better (p < 0.01) than that of 52% for patients with high grade disease. Different treatment methods--surgery, chemotherapy, or a combination of both--did not significantly affect survival. Low grade tumours occurred mainly in men with a history of several years, and who presented with non-specific gastric symptoms without remarkable exploratory or laboratory findings: most patients were in stage IE-IIE and achieved remission and cure. High grade can have a shorter history, systemic symptoms, abnormal exploratory and laboratory findings, gastric tumour masses, stage IV disease, and a worse outcome. The only significant prognostic factors for survival were the type of lymphoma and stage IV disease. These findings support the Isaacson classification system which separates two extreme groups of gastric lymphomas with different morphology, behaviour, and outcome. The presence of limited areas of high grade in a specimen showing low grade does not change the outcome but suggests that primary gastric lymphoma forms a continuum between these extreme types. PMID- 1446851 TI - Changing pattern of gastric cancer in Oxfordshire. AB - This study compares the incidence rates of histologically confirmed gastric carcinoma in Oxfordshire in two five year periods (1960-64, 1984-88). Data were available for 215 patients in the first period, and 200 in the second. The overall incidence fell from 18/100,000 to 15/100,000 but when analysed for site, the incidence of antral tumours fell from 10 to 4.5/100,000. In contrast, there was an increase from 2.8 to 5.2/100,000 of tumours of the cardia. These changes were more pronounced in men. There was a marked association between smoking and tumours of the cardia (relative risk 4.5). Helicobacter pylori was associated with 37.5% of tumours in the 1960s series compared with 25% in the later series. The changing patterns of incidence of gastric carcinoma may, in part, be related to changes in smoking habits and perhaps a change in incidence of H pylori infection. PMID- 1446852 TI - Early gastric cancer: 46 cases treated in one surgical department. AB - Forty six consecutive patients with early gastric cancer were treated between 1970 and 1990. The proportion of cases of early gastric cancer increased significantly (p < 0.01) from 1% of all cases in the first five year period to 15% in the last five year period, because of greater awareness of the condition and more widespread use of endoscopy. There were 33 men and 13 women, of median age 69 years (range 38-86). Most patients (91%) presented with symptoms indistinguishable from those of peptic ulceration. The median duration of symptoms was four months (range 0.1-36 months). All 46 patients were treated surgically. Three patients (6.5%) died after operation and a further 10 (22%) suffered postoperative complications. None of the surviving patients has been lost to follow up and 25 have been followed up for a minimum period of five years. Five year survival by life table analysis was 98%. These findings suggest that in Britain in the 1990s, as in Japan, it may be possible to diagnose an increasing proportion of patients with gastric cancer at a relatively early pathological stage, when most patients can be cured by radical surgical resection with lymphadenectomy. PMID- 1446853 TI - Evidence of clonal variants of Helicobacter pylori in three generations of a duodenal ulcer disease family. AB - Nine members of a family with a high incidence of duodenal ulcer disease were studied by interview, examination of hospital records, endoscopy, and antral biopsy. Helicobacter pylori was confirmed by CLO test, histology and culture. DNA extraction from pure isolates of H pylori was possible in six family members and strain typing was performed by restriction fragment length polymorphism. DNA restriction digestion was followed by vacublotting and then DNA hybridisation, using a cDNA probe complimentary to H pylori rRNA cistrons. Eight of the nine family members were H pylori positive by CLO test and histology. Five had duodenal ulcer disease. Three family members (one from each generation) harboured clonal variants of a single parent strain of H pylori but only two had duodenal disease. The other three members harboured different strains. Intrafamilial clustering of clonal variants of H pylori occurs in some duodenal ulcer disease families. Family members however, may develop duodenal disease irrespective of the colonising strain. PMID- 1446854 TI - Eighteen month follow up of Helicobacter pylori positive children treated with amoxycillin and tinidazole. AB - Sixty three children with dyspepsia (mean age 12 years, range one to 18, M/F 41/22) were Helicobacter pylori positive by histology of gastric antral biopsy specimens and were treated with a six week course of amoxycillin (50 mg/kg) and tinidazole (20 mg/kg). The endoscopic diagnoses were: normal (16), nodular gastritis (19), oesophagitis (four), duodenal ulcer (13), and gastric ulcer (11). H pylori was eradicated in 54 (87%) and histological gastritis resolved in 51 and was improved in the other three. Repeat investigation was offered at six monthly intervals. Reinfection was found in three of 34 (9%) at six months, in none of 22 at 12 months, and in two of 18 (11%) at 18 months, yielding an 18 month cumulative relapse rate of 20%. Children with persisting infection despite treatment remained positive during follow up. Serum H pylori IgG concentrations fell after treatment (p < 0.001), and for individual children during follow up there was a progressive decline, but an increased concentration indicated recurrence. After eradication of H pylori by combined amoxycillin and tinidazole treatment, only a minority of children relapse during the ensuing 18 months. PMID- 1446855 TI - Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people. AB - Fifteen healthy old people mean age 84 years (range 80-91 years), were examined to assess the effect of advanced age on the microecology of the upper gastrointestinal tract. Twelve of 15 (80%) were hypochlorhydric with pH 6.6 (0.3) (mean (SEM) and a mean bacterial count of 10(8) colony forming units (CFU) per ml (range 10(5)-10(10)) in fasting gastric aspirate. Normochlorhydric subjects had low counts (< or = 10(1) CFU/ml). The microbial flora was dominated by viridans streptococci, coagulase negative staphylococci, and Haemophilus sp. Only one subject harboured significant concentrations of Gram negative bacilli with Escherichia coli (10(4-5) CFU/ml) and Klebsiella (10(4-5)). Strict anaerobes were not found. The total concentration of short chain fatty acids in gastric aspirate was 10.6 (2.9) mmol/l (mean (SEM). Absence of significant, intraluminal fermentation of xylose to CO2 was shown by the 14C-d Xylose breath test, and ambulatory manometry showed preserved fasting motility pattern of the small intestine. Serum immunoglobulins were normal. Advanced age is accompanied by fasting hypochlorhydria and colonisation with mainly Gram positive flora in the upper gut. Other factors than old age and fasting hypochlorhydria are required for colonisation with Gram negative bacilli. PMID- 1446856 TI - Concentrations of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations. AB - Intramucosal 5-aminosalicylic acid (5-ASA) and acetylated 5-ASA (Ac-5-ASA) concentrations were determined in ileocolonic biopsy specimens from 61 patients with irritable bowel syndrome treated for one week with near equimolar doses of different slow release preparations of 5-ASA (Claversal, Asacol, or Pentasa) or azo-bound drugs (Salazopyrin, Dipentum). The transit time in these patients was accelerated by a laxative, metoclopramide, and colonic lavage. The presence of 5 ASA in the mucosa was confirmed by autofluorescence. The highest concentrations of 5-ASA were obtained after Asacol (mean (SEM), 298.5 (37.3) ng/mg wet wt), followed by Claversal 500 mg (108.8 (11.7) ng/mg wet wt) and Pentasa (25.7 (2.2) ng/mg wet wt). Very low concentrations only were observed after Claversal 250 mg (0.3 (0.03) ng/mg wet wt), Salazopyrine (1.2 (0.1) ng/mg wet wt), and Dipentum (11.0 (3.2) ng/mg wet wt). The results for Ac-5-ASA were similar but the concentrations were generally lower. Serum concentration-time curves over eight hours were obtained from 34 healthy volunteers after a single oral dose of 400 to 500 mg of the different drugs. For the slow release forms, an apparently inverse relationship was found between the area under the curve of the serum concentrations and the intramucosal concentrations, supporting the importance of the local availability of the drug. This inverse relationship was absent for the azo-bound drugs. Colonic washout induced mechanical removal of intraluminal 5-ASA with a secondary disturbance in absorption resulting in a rapid decline in the serum concentrations. However, only for Dipentum did this result in significantly lower 5-ASA mucosal concentrations. This is the first reported attempt to evaluate the mucosal availability of 5-ASA after different oral preparations. It shows that where transit time is accelerated higher mucosal concentrations occur after slow release preparations (except for Claversal 250 mg) than after azo bound drugs. Additional studies are necessary to correlate these concentrations with clinical effects. PMID- 1446857 TI - Comparison of 5-aminosalicylic acid and N-acetylaminosalicylic acid uptake by the isolated human colonic epithelial cell. AB - Isolated human colonic epithelial cell suspensions were incubated with either 0.1 mM 5-aminosalicylic acid (5-ASA) or 0.1 mM acetylaminosalicylic acid (Ac-ASA) for up to two hours. Intra- and extracellular 5-ASA and Ac-ASA were measured by high performance liquid chromatography. Mean 5-ASA uptake in one hour was 160.5 nmol/g dry weight, compared with an Ac-ASA uptake of only 5.75 nmol/g dry weight. No unchanged 5-ASA was detected inside the cell. Repeated washing had no effect on the intracellular Ac-ASA concentration. This discrepancy in drug uptake may explain why Ac-ASA seems to be ineffective when given to patients with ulcerative colitis. PMID- 1446858 TI - Tests of renal function in patients with quiescent colitis: effects of drug treatment. AB - Mesalazine has structural similarities to aspirin and phenacetin and is nephrotoxic when given intravenously in high doses to rats. A number of cases of nephrotoxicity has been reported recently in patients taking oral mesalazine. Sensitive indicators of renal function in a group of patients maintained on long term, delayed release mesalazine and a comparable group on sulphasalazine have been studied. Sixty two patients (32 men, aged 28-82 years) with quiescent colitis were studied. Thirty four had been maintained on delayed release mesalazine 1.6 (0.8-2.4) g/day for 2.9 (0.5-6.9) years and 28 on sulphasalazine 2 (2-3) g/day. Groups were comparable for age, sex, disease duration, and disease extent. Renal function was assessed by: urine microscopy; creatinine clearance; the urinary excretion of two markers of glomerular toxicity, albumin and transferrin; and the urinary excretion for two markers of tubular toxicity, N acetyl-beta-D-glucosaminidase (NAG) and alpha 1-microglobulin. There were no significant differences in renal function between the two treatment groups. Furthermore, no correlations were found between measures of renal function and either cumulative mesalazine dose or mesalazine treatment duration. In this study, long term maintenance treatment with delayed release mesalazine was no more nephrotoxic than continued treatment with sulphasalazine. PMID- 1446859 TI - Inhibition of binding of interferon-gamma to its receptor by salicylates used in inflammatory bowel disease. AB - 5-Aminosalicylic acid (5ASA), 4ASA, their N-acetylated metabolites N-acetyl-5ASA and N-acetyl-4ASA, olsalazine, and colchicine impair interferon-gamma (IFN gamma) induced HLA-DR expression on a colonic cell line, HT-29. The mechanism of this effect is now reported. HT-29 cells were cultured with 50 U/ml IFN gamma with or without drug, and northern blot analysis was performed using a probe for the beta chain of the DR molecule. IFN gamma led to a noticeable increase in HLA-DR mRNA which was attenuated by the drugs. Analysis of the specific binding of increasing concentrations of 125I-IFN gamma by non-linear regression showed a Kd of 1.35 x 10(-10) M and 2.3 x 10(5) binding sites per HT-29 cell. Binding of 125I-IFN gamma was reduced by incubation with increasing concentrations of unlabelled IFN gamma but not with IFN alpha. Incubation with therapeutic concentrations of drugs led to the following reductions in binding: 10 mM 5ASA, 20% (p < 0.001); 10 mM N acetyl-5ASA, 24% (p < 0.01); 10 mM 4ASA, 21% (p < 0.005); 10 mM N-acetyl-4ASA, 29% (p < 0.001); and 1 mM olsalazine, 29% (p < 0.001). Colchicine (10(-7) M) and 10(-5) M prednisolone had no effect. Incubation with higher concentrations of the drugs revealed a dose-response effect on binding with complete inhibition by 100 mM 4ASA and 10 mM olsalazine, and lesser degrees of inhibition by 100 mM 5ASA, N acetyl-5ASA, and N-acetyl-4ASA. At concentrations found in the rectal lumen, the salicylates used in inflammatory bowel disease impair the binding of IFN gamma to its receptor on colonic epithelial cells. PMID- 1446860 TI - IgG subclass distribution in serum and rectal mucosa of monozygotic twins with or without inflammatory bowel disease. AB - Serum samples from 26 monozygotic twin pairs concordant or discordant with regard to inflammatory bowel disease, and rectal biopsies from 42 twins of the same subject group, were examined for IgG subclasses. They were all compared with normal controls. Almost all affected twins were in clinical remission. Paired immunofluorescence staining of the rectal mucosa showed that those with ulcerative colitis had a significantly higher (p < 0.01) proportion of IgG1 producing mucosal immunocytes than normal controls (78.1% v 55.9%). Conversely, the IgG2 cell fraction was significantly reduced (15.9% v 34.6%). Healthy twins from ulcerative colitis pairs tended to show a raised proportion of IgG1 cells and the IgG2 cell fraction was significantly reduced (p < 0.05). In discordant ulcerative colitis twin pairs, no difference appeared in the cellular IgG subclass pattern between healthy and affected twins. Furthermore, the proportion of IgG1 in these healthy and diseased twins showed good correlation (T = 0.867). The results in rectal mucosa of twins with Crohn's disease were widely scattered and affected twins did not differ significantly from normal controls. Healthy twins, however, showed a marginally raised IgG1 cell proportion, but no correlation was seen between the IgG subclass fractions in discordant Crohn's disease twin pairs. The serum concentrations of IgG1 and IgG2 did not differ from normal controls in twins of either category. These results suggested that in ulcerative colitis, the aberrant mucosal production of IgG1 and IgG2 does not depend on active disease, but is apparently at least partially explained by a genetic impact. Conversely, the mucosal IgG subclass pattern in Crohn's disease appears to be determined mainly by exogenous variables. PMID- 1446861 TI - Plasma polyunsaturated fatty acid pattern in active inflammatory bowel disease. AB - Plasma fatty acid patterns were assessed by gas liquid chromatography in 73 patients with active inflammatory bowel disease and 107 healthy controls. The influence of the disease activity on fatty acid profile was also investigated. Plasma fatty acid patterns in patients with ulcerative colitis and Crohn's disease were similar. Plasma C18:3n3 and C22:6n3 were significantly higher in active ulcerative colitis (p = 0.0143 and p < 0.00001 respectively) and in Crohn's disease (p < 0.00001 for both) than in controls, whereas C20:3n6 was significantly lower in patients than in controls, both in ulcerative colitis (p = 0.0001) and in Crohn's disease (p = 0.0041). In more severe disease, plasma polyunsaturated fatty acid concentrations fell with a significant stepwise decrease in the desaturation index (p = 0.0031 in ulcerative colitis and p = 0.0355 in Crohn's disease). Even in patients with severe disease, however, plasma n3 fatty acids (C18:3n3 and C22:6n3) never fell below those of healthy controls. These findings suggest that in active inflammatory bowel disease, an increased biosynthesis might coexist with an increased consumption of polyunsaturated fatty acids. These observations may be of relevance in the pathogenesis of the disease as polyunsaturated fatty acids are involved in tissue eicosanoid synthesis and cellular membrane function, including that of immunocompetent cells. These results also question the rationale of using n3 polyunsaturated fatty acids in the treatment of inflammatory bowel disease. PMID- 1446862 TI - Prevalence of anti-neutrophil antibody in primary sclerosing cholangitis and ulcerative colitis using an alkaline phosphatase technique. AB - The detection of a nuclear anti-neutrophil antibody in patients with primary sclerosing cholangitis (PSC), using an immunoperoxidase technique, was recently reported by us. Subsequently, detection of a cytoplasmic anti-neutrophil antibody was reported by others, using a two stage procedure of enzyme linked immunosorbent assay followed by an immunofluorescent method. Detection of cytoplasmic anti-neutrophil antibody in PSC, which, in contrast to that two stage procedure, uses a simple one step immuno-alkaline phosphatase method is now reported. Normal human neutrophils were cytocentrifuged, ethanol fixed, and then incubated with coded patients' sera. Rabbit anti-human immunoglobulin conjugated with alkaline phosphatase was used to detect the bound antibody. Fast red was used to visualise the reaction. Twenty three of 30 (77%) PSC patients showed positive granular cytoplasmic staining (with some perinuclear accentuation) with a network of cytoplasmic filaments. Fifteen of 45 (33%) ulcerative colitis patients and 1 of 3 chronic active hepatitis patients showed similar staining. Thirty five of 152 patients with ulcerative colitis, chronic active hepatitis, and a variety of other liver diseases showed a different pattern of cytoplasmic labelling, with no surrounding filaments. Seventy nine patients, including seven PSC patients and 33 normal subjects, were negative. In comparison, 86% of PSC patients, 57% of patients with primary biliary cirrhosis, 50% of normal subjects, and well over 60% of patients with ulcerative colitis, Crohn's disease, alcoholic liver disease, and chronic active hepatitis were positive using the one step immunofluorescent method. This method is more specific for PSC than those described in recent reports and may be of diagnostic importance. PMID- 1446863 TI - Sclerosing cholangitis and biliary tract calculi--primary or secondary? AB - The clinical features of 61 patients with sclerosing cholangitis were reviewed. This group included 23 patients with biliary tract calculi, commonly considered as excluding the diagnosis of primary sclerosing cholangitis. The aim of this study was to compare these 23 patients (group A) with 38 patients with sclerosing cholangitis free of calculi (group B). Both groups had the following features in common: (i) age at presentation, (ii) incidence of inflammatory bowel disease, (iii) extent of radiological disease, (iv) prevalence of HLA-B8 and DR3 haplotype, (v) incidence of cholangiocarcinoma, and (vi) progression to hepatic transplantation (mean follow up 49.9 months). All patients in group A were symptomatic at diagnosis compared with 23 of the 38 patients (61%) in group B. Recurrent ascending cholangitis occurred in 12 patients in group A (52%) and two patients (5%) in group B. The similarity between the two groups was maintained when the nine patients in group A who developed calculi after sclerosing cholangitis was diagnosed were excluded. It is concluded that choledocholithiasis is part of the spectrum of primary sclerosing cholangitis and that it is not necessary to invoke choledocholithiasis as the initial lesion of the bile ducts in such patients. PMID- 1446864 TI - Factors related to early mortality in cirrhotic patients bleeding from varices and treated by urgent sclerotherapy. AB - Variceal haemorrhage in cirrhotic patients carries a high early mortality even when balloon tamponade or emergency sclerotherapy are applied. The aim of this study to identify patients dying within six weeks of their first variceal haemorrhage. One hundred and twenty one patients with parenchymal cirrhosis presenting with the first variceal bleeding episode between June 1983 and December 1988 were studied. Nineteen patients were excluded for various reasons. Emergency sclerotherapy was carried out in cases of active bleeding or where there were endoscopic signs of recent bleeding, and then regularly repeated afterwards. Of the 24 variables studied and included in a multivariate analysis using a logistic regression model, three had an independent prognostic value: encephalopathy, prothrombin time, and the number of blood units transfused within the 72 hours of time zero. The subsequent regression equation was able to predict 89% of the patients who will die and 97% of the patients who will still be alive six weeks after their first variceal haemorrhage treated by sclerotherapy. Pugh score was less discriminatory than these last three variables in terms of accuracy of adjustment, goodness of fit to the model, receiver operating characteristic curves, and percentage correct prediction. To measure the accuracy of the prediction rule, our model was applied to another series of 28 cirrhotic patients admitted with their first variceal bleeding during the next period (January 1989 to May 1990). Death and survival were correctly predicted in respectively 82% and 94% of the cases. The use of this score is recommended for the selection of patients with high early mortality after variceal bleeding despite sclerotherapy, and for the design of new therapeutic trials. PMID- 1446865 TI - Splenic function in alcoholic liver disease. AB - Splenic function was assessed in 42 patients with alcoholic liver disease by counting the percentage of erythrocytes with indentations or pits, seen by differential interference contrast microscopy. These pits represent cellular debris normally removed by the spleen. The findings were compared with 42 age and sex matched controls. Mean (SEM) pitted red cell counts in the patients was 2.7 (0.4)% and in the controls 0.7 (0.07)% (p < 0.001). In all of the eight reformed drinkers (five with biopsy proven cirrhosis), cell counts were normal. Six patients with alcoholic liver disease had had serious infections within the past year. Of these, one had had a recent pneumococcal pneumonia and another of the patients died from overwhelming pneumococcal septicaemia. Both of these patients had evidence of functional hyposplenism as judged by high pitted erythrocyte counts. A total of 18 patients were considered to have pitted red cell counts above the normal, and 11 of these had proven cirrhosis and/or gross ascites. This study is the first to show the presence of functional hyposplenism in alcoholic liver disease and provides further evidence of the predisposition that these patients have to infection. At present, it is unclear whether the hyposplenism is a direct toxic effect of alcohol or the result of cirrhosis; further studies are warranted. PMID- 1446866 TI - Recurrence of hepatitis B and delta hepatitis after orthotopic liver transplantation. AB - The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function. PMID- 1446867 TI - Liver disease in a district hospital remote from a transplant centre: a study of admissions and deaths. AB - The profile of liver disease admissions and associated deaths in a district general hospital was studied to determine whether patients with end stage liver disease are appropriately referred for consideration of liver transplantation. Admission details were provided by the Office of Population Censuses and Surveys (OPCS) and their accuracy was assessed by case note analysis. According to OPCS, 77 patients with liver disease were admitted on 113 occasions between 1 January 1987 and 31 December 1989. The case notes of 74 (96%) were retrieved and examined. Only 64 (86%) had primary liver disease. Twenty four (31%) died of liver failure. Alcohol was the aetiological agent in two thirds. According to accepted criteria, 11 patients were suitable for liver transplant assessment but only three had been referred to a transplant centre. Of the remaining eight, five died during the study period. Two of the three patients referred died without transplantation; one underwent transplant and survived. There is discrepancy between OPCS data and true disease aetiologies, with approximately 40% under reporting of alcoholic liver disease. If this population is representative of the situation nationally, substantial numbers of patients with end stage liver disease might benefit from liver transplantation, but are not referred to a centre. PMID- 1446868 TI - Effect of lipid infusion on bile composition and lithogenicity in patients without cholesterol gall stones. AB - A prospective study was performed to investigate the effect of short term lipid infusion on bile composition and its lithogenicity in humans. Thirty five patients shown to be free of cholesterol gall stones participated in the study. Starting 48 hours before surgery they were infused randomly with a lipid emulsion of either long chain triglycerides (LCT) or a mixture of medium and long chain triglycerides (MCT/LCT) (50%/50%) for six hours each 24 hours. A group of patients infused with a solution of 5% glucose in NaCl 0.9% served as a control. Bile samples were obtained by puncture of the gall bladder during operation. Both lipids caused an increase in biliary cholesterol and phospholipids but this effect was more pronounced and significant (p < 0.001) only with the MCT/LCT emulsion. The fatty acid composition of biliary phospholipids was not affected by either lipid infusion. The cholesterol saturation index increased significantly (p < 0.005) with the MCT/LCT emulsion and there was shortening in the nucleation time but this was not significant. There was no effect on the distribution of cholesterol between micelles and vesicles. This study shows that infusion of MCT/LCT lipid emulsion can cause lithogenic changes in bile composition in humans and may thus contribute to sludge formation and cholelithiasis during long term parenteral nutrition. PMID- 1446869 TI - Increased activity of ionised calcium in gall bladder bile in gall stone disease. AB - The actual activity of ionised calcium (Ca2+) in gall bladder bile determined with an ion-selective electrode was significantly higher in patients with gall stone disease (n = 15) than in patients without gall stones (n = 10) (0.43 mmol/kg v 0.31 mmol/kg; p < 0.05). No change in the Ca2+ activity in any of the gall bladder bile samples was observed during equilibration with CO2. During titration with HCl/NaOH, however, the Ca2+ activity fell with increasing pH in a biphasic manner, with the breaking point occurring at a significantly lower median pH in patients with gall stones than in patients without (pH 7.1 v 8.2; p < 0.0001). The combination of a higher activity of calcium in bile and precipitation of bile salts taking place at a lower pH in patients with gall stone disease than in patients without gall stones suggests a major role for calcium and pH in the pathogenesis of gall stones. Strict anaerobic sampling is not necessary for the measurements of Ca2+ in gall bladder bile, because the Ca2+ was not significantly affected by the changes in pCO2. The metabolic studies suggest, however, that simultaneous measurements of the activity of Ca2+ and pH is important in order to interpret data for the calcium activity in gall bladder bile. PMID- 1446870 TI - Value of exfoliative cytology for investigating bile duct strictures. AB - The cause of a biliary tract stricture may be difficult to determine radiologically. Exfoliative biliary cytology was evaluated in 62 patients (median age 65 years, range 30-94) with biliary tract strictures presenting to the Hepatobiliary Unit between January 1984 and December 1989. Bile samples were taken during endoscopic retrograde cholangiopancreatography (ERCP) in 42 patients, percutaneous cholangiography in 14, and both in six. The site of stricturing was upper third of the bile duct in 43% (n = 27), middle third in 10% (n = six), and lower third in 47% (n = 29). Of the 47 patients with radiological appearances of a malignant stricture, 22 (47%) had histological confirmation by biopsy either under computed tomography guidance, at endoscopy, at operation, or at necropsy. Fourteen of the 47 patients had positive cytology (30%). In seven patients cytology alone established the presence of malignancy (15%) and in the other seven positive cytology was confirmed by histology. The addition of cytology to tissue biopsy therefore allowed malignancy to be confirmed in 29 of the 47 patients (62%). None of the 15 patients subsequently shown to have benign disease had positive cytology. Sensitivity of the technique was 30% and specificity 100%. Samples for exfoliative cytology are simple to obtain, the results are highly specific and should be a routine part of the investigation of biliary strictures. PMID- 1446871 TI - Management of common bile duct stones with a biliary endoprosthesis. Report on 40 cases. AB - Endoscopic placement of a biliary endoprosthesis has been proposed for the management of choledocholithiasis when stone extraction is difficult or considered hazardous. Over a two year period this approach was used in 40 such patients. There were 24 women and 16 men with a median age of 76 years. In seven patients with severe cholangitis no attempt was made to extract the stones. Twenty three (57.5%) patients underwent a sphincterotomy and four (10%) needle knife papillotomy. The endoprosthesis insertion was considered a temporary measure in 13 (32.5%) patients and definitive treatment in 27 (67.5%). Bile duct drainage was established in all patients. Early complications occurred in six patients (15%), but were without sequelae. Late complications developed in eight (20%) of the patients and included biliary colic (four), cholangitis (three), and cholecystitis (one). Two patients (one cholangitis and one cholecystitis) died as a consequence of the complication. Only patients without a sphincterotomy developed cholangitis. A total of eight patients (20%) underwent surgery (one as an emergency) and nine a repeat endoscopic retrograde cholangio pancreatography (two as an emergency) to clear the duct. The remaining 23 patients are asymptomatic at a median of 13 months (range five to 24 months). Biliary endoprosthesis insertion for choledocholithiasis is an important alternative means of establishing drainage in selected cases, and is probably the optimum method of management for the elderly and or debilitated patients with previous cholecystectomy. Caution must be exercised, however, in patients with an in situ gall bladder. PMID- 1446872 TI - Extracorporeal shock wave lithotripsy of bile duct stones: a single institution experience. AB - Extracorporeal shock wave lithotripsy treatment with Dornier HM3 or MPL 9000 machines was applied in 37 patients with problematic bile duct stones. General anaesthesia was not required. After one extracorporeal shock wave lithotripsy session 14/37 patients (38%) were spontaneously stone free, and additional endoscopic extraction (eight of 37) and retreatments with extracorporeal shock wave lithotripsy (seven cases) increased the stone free rate to 29/37 (78%). In three patients with intrahepatic stones, the bile ducts could not be evaluated decisively at cholangiography and ultrasonography, but they were all symptom free at 15 to 38 months follow up. If these three patients are added to the radiologically stone free patients, the overall clinical success rate was 32/37 (86%). There were no serious complications, hospital admissions, or 30 day mortality as a result of extracorporeal shock wave lithotripsy or endoscopic procedures. It is concluded that extracorporeal shock wave lithotripsy is a valuable adjunct to the non-surgical treatment of bile duct stones. PMID- 1446873 TI - Familial coexistence of achalasia and non-achalasic oesophageal dysmotility: evidence for a common pathogenesis. AB - In five of seven siblings of healthy parents, dysphagia developed during adolescence or early adult life. A barium swallow was normal in one patient but showed appearances considered to be consistent with achalasia in all others. Oesophageal manometry was successfully performed in four of the five patients, including the patient with symptoms but normal radiological appearance. One patient had achalasia, two had oesophageal body motor dysfunction associated with a hypertensive, but normally relaxing lower oesophageal sphincter, and one had diffuse oesophageal spasm alone. The occurrence of three different oesophageal dysmotility disorders within members of a single sibship suggests that these conditions are intimately related and probably genetically determined as an autosomal recessive trait. PMID- 1446874 TI - Non-steroidal anti-inflammatory drug-induced jejunal and colonic diaphragm disease: a report of two cases. AB - Two patients with intestinal submucosal diaphragm disease associated with non steroidal anti-inflammatory drugs are presented. The jejunum was affected in one, and in the other the ascending colon. Most previously reported cases have shown ileal disease and no case to date has shown involvement of the colon. The reasons for the localisation of these diaphragms remain unclear. PMID- 1446875 TI - Ulcerative colitis complicated by Wenckebach atrioventricular block. AB - Extracolonic manifestations of inflammatory bowel disease are common and diverse. Cardiac complications, however, are rare and of these pericarditis is the most frequently described association. A 57 year old man with a 20 year history of ulcerative colitis presented with a four day history of retrosternal chest pain and exertional dyspnoea. Electrocardiogram showed Wenckebach atrioventricular block. Three days later he developed bloody diarrhoea and sigmoidoscopy showed active proctocolitis. He was treated with oral prednisolone after which the chest pain and diarrhoea settled within 48 hours. At outpatient review two weeks later he was completely well and the electrocardiogram had returned to normal. PMID- 1446876 TI - Sclerosing cholangitis associated with multifocal fibrosis: a case report. AB - The association of sclerosing cholangitis, retroperitoneal fibrosis, and Riedel's thyroiditis has been reported twice before, and on both occasions the authors successfully used steroids to control the fibrotic process. A further case of fibrosis with this triad of organ involvement in which a combination of surgery and steroid treatment has arrested disease progression is described. This suggests an inappropriate immune response in this type of fibrotic overlap syndrome. PMID- 1446877 TI - Piroxicam induced submassive necrosis of the liver. AB - Several widely used non-steroidal anti-inflammatory drugs have been reported as causing severe hepatitis. Three cases of severe acute hepatitis have been reported in association with piroxicam. A fatal submassive necrosis that occurred in a 68 year old lady who had received piroxicam for 15 months is described. A 48 year old man who developed submassive hepatic necrosis six weeks after beginning piroxicam but was successfully treated with orthotopic liver transplantation is also reported. Piroxicam may induce submassive necrosis of the liver, probably as an idiosyncratic reaction. PMID- 1446878 TI - Ultrarapid urease test. PMID- 1446879 TI - [Effects of ambroxol HCl on the guinea pig tracheal mucous secretion and the rat pulmonary surfactant secretion]. AB - The effects of orally administered ambroxol HCl (ambroxol) on guinea pig tracheal mucous secretion and rat pulmonary surfactant secretion were investigated histologically and biochemically. Ambroxol significantly increased the number of active goblet cells in guinea pig tracheal epithelium and total mucopolysaccharide level. Moreover, ambroxol significantly increased the neutral mucopolysaccharide level and PAS-positive substance in the guinea pig tracheal submucosal glands. Ambroxol did not show a significant effect on the content of the total phosphatidylcholine in rat lung lavage fluid, while ambroxol significantly increased the ratio of disaturated phosphatidylcholine to total phosphatidylcholine. From these results, it is suggested that ambroxol increases both the tracheal mucous secretion, especially the neutral mucopolysaccharide, and pulmonary surfactant secretion and these effects reflect part of the expectorant mechanism of the drug. PMID- 1446880 TI - [Effects of drugs on the convulsions induced by the combination of a new quinolone antimicrobial, enoxacin, and a nonsteroidal anti-inflammatory drug, fenbufen, in mice]. AB - The effects of drugs on the convulsions induced by the combination of a new quinolone antimicrobial, enoxacin, and a nonsteroidal anti-inflammatory drug, fenbufen, were studied in mice. The combination of enoxacin at 30 or 100 mg/kg, p.o. and fenbufen at 100 mg/kg, p.o. induced convulsions; and the mice died as a result of the convulsions. Pretreatment with either phenobarbital, phenytoin, valproic acid intraperitoneally, or morphine intravenously did not influence the convulsions. A high dose of diazepam or clonazepam prolonged the survival time, but could not prevent the mice from dying. After the occurrence of convulsions induced by enoxacin with fenbufen, administration of the excitatory amino acid antagonist MK-801 at 1 mg/kg, i.v. extended the survival time, even though all the mice died as a result of the convulsions. Simultaneous intravenous injections of MK-801 and diazepam suppressed the convulsions. This suppression was stronger than that produced by MK-801 or diazepam, injected separately. However, no mouse survived at the end. From these results, participation of both GABA-ergic and excitatory amino acidergic systems in the convulsions induced by enoxacin and fenbufen was discussed. PMID- 1446881 TI - [Analgesic effects of Tsumura-shuuji-bushi-matsu and mesaconitine]. AB - "Tsumura-shuuji-bushi-matsu" (TJ-3021) is a herbal medicine produced from Aconiti tuber through autoclaving to decrease its toxicity. In this study, the analgesic effects of TJ-3021 and mesaconitine (MA) was examined in rats and mice. TJ-3021 (300 mg/kg, p.o.) or MA (0.5 mg/kg, p.o.) depressed the acetic acid-induced writhing significantly. In Randall-Selitto's method, TJ-3021 (1000 mg/kg) increased the pain threshold ratio in the inflamed foot significantly but not in the normal foot. In the hot plate method or on adjuvant-induced arthritic pain, TJ-3021 (1000 mg/kg) significantly increased the pain threshold, and its effect was less than that of "nama-bushi-matsu" (TNB), which was produced from the same Aconiti tuber without autoclaving. Repeated cold stress (RCS) for 65.5 hr decreased the pain threshold ratio on the paw pressure in rats by 60%. TJ-3021 (300 mg/kg) significantly increased the pain threshold ratio in RCS rats, and its activity was almost the same degree as that of TNB. MA (0.5 mg/kg) significantly increased the pain threshold ratio in RCS rats or on the adjuvant-induced arthritic pain; and in RCS rats, it was more potent than morphine (1 mg/kg, p.o.). PMID- 1446882 TI - [The vasospasmolytic effects of nicorandil, cromakalim and pinacidil on 3,4 diaminopyridine-induced phasic contractions in canine coronary arteries as an experimental vasospasm model]. AB - The spasmolytic mechanisms of nicorandil, a novel antianginal drug, were investigated using 3,4-diaminopyridine (3,4-DAP)-induced phasic contractions of isolated canine coronary arteries in comparison with those of cromakalim and pinacidil. Nicorandil (10(-4) M), cromakalim (10(-6) M) and pinacidil (10(-5) M) suppressed the phasic contractions. Pretreatment with glibenclamide (10(-6) M), a specific blocking agent of ATP-sensitive K+ channel, eliminated the suppression of phasic contractions by these drugs; glibenclamide completely eliminated the suppression by cromakalim, while the eliminations against nicorandil and pinacidil were incomplete. The recoveries of peak tensions were only 56.8% and 76.1% for nicorandil and pinacidil, respectively. Nicorandil and pinacidil may suppress the phasic contractions via K+ channel opening and additional mechanisms. Methylene blue (10(-7)-10(-5) M) alone, a guanylate cyclase inhibitor, had no effect on the suppression of phasic contractions by nicorandil. In the presence of glibenclamide (10(-6) M), however, the pretreatment with methylene blue significantly augmented the recovery of peak tension for nicorandil. These results indicate that K+ channel openers may suppress the phasic contractions induced by 3,4-DAP via ATP-sensitive K+ channels, and that additionally, nicorandil may suppress the phasic contractility through guanylate cyclase stimulation, as a nitrate. PMID- 1446884 TI - [Inhibitory effects of Siamese Tinospora crispa extracts on the carrageenin induced foot pad edema in rats (the 1st report)]. AB - The naturally occurring Tinospora crispa (T.c.) at Chiang Mai in Thailand has been found to inhibit carrageenin-induced foot pad edema. Compared with the control group, oral administration of the 50% methanol extract (10 mg/kg) from its stems inhibited the edema by 38% in volume, which was induced 4 hr after stimulation by carrageenin in rats. This inhibitory effect on edema formation has been most significant in the n-butanol soluble fraction compared with the ethyl ether- or water-soluble ones, and the action of the n-butanol fraction has been observed in a dose-dependent manner in the range of 1 to 30 mg/kg, p.o. Administration of this fraction by the s.c., or i.p. route also inhibited the carrageenin-induced edema formation to the same degree as that by the oral route. The 3 mg/kg, s.c. dosage of the fraction corresponds roughly to 250 mg/kg sulpyrine and 10 mg/kg diphenhydramine, s.c. Moreover, the fraction administered i.v. also reduced LPS-induced fever in rabbits, and had an antagonistic effect equivalent to 100 mg/kg sulpyrine and 1 mg/kg morphine hydrochloride (in i.p. administration). The comprehensive anti-inflammatory substance(s) contained in T.c. stems are moderately non-polar compounds soluble in n-butanol and absorbable from both walls of the gut and vessels. The usefulness of a modified dosage of this plant extract for clinical treatment of various types of inflammation is highly suggested. PMID- 1446883 TI - [Effects of tiropramide hydrochloride on the isolated detrusor and intravesical pressure of the bladder in situ in rats]. AB - The effects of tiropramide on the isolated detrusor and intravesical pressure of the bladder in situ in rats were compared with those of flavoxate, oxybutynin and terodiline. The IC50 values (x 10(-5) M) of tiropramide for carbachol (CCh)-, K+ (60 mM)-, Ba2+ (10 mM)-, and electrical stimulation-induced contractions were 3.6, 4.2, 5.8, and 2.9, respectively. The four antispasmodics used (2 and 4 mg/kg, i.v., each) abolished the rhythmic bladder contractions in situ in anesthesized rats. Of the four compounds, oxybutynin was most potent and no significant differences were observed between the inhibitory effects of tiropramide, flavoxate and terodiline. The administration of flavoxate (30 and 60 mg/kg) into the duodenum little influenced the rhythmic bladder contractions. Tiropramide, flavoxate, oxybutynin and terodiline (8 and 12 mg/kg, i.v., each) dose-dependently prolonged the time to the volume-evoked micturition reflex, and the activity of tiropramide was not statistically different from those of the other three antispasmodics. Under unilateral pelvic and bilateral hypogastric nerve transection, both of the contractions induced by electrical stimulation of the peripheral and central cut ends of the pelvic nerve were dose-dependently inhibited to the same extent by tiropramide and terodiline. These results suggest that the effects of tiropramide on the function of urinary bladder in rats may be mainly due to direct actions on the smooth muscle, and that tiropramide is more potent than flavoxate and less potent than oxybutynin and terodiline. PMID- 1446885 TI - [Effects of Gomishi and Shosaiko-to on lipid peroxidation of rat brain]. AB - Gomishi and Shosaiko-to were administered to the rats at a dose of 10-100 mg/kg daily for 2 weeks, and their effects on lipid peroxidation of rat brain were compared with that of alpha-tocopherol. Administration of Gomishi and Shosaiko-to showed almost the same suppressive action on the lipid peroxidation. Gomishi and Shosaiko-to exhibited a radical-trapping action on a stable free radical, 1, 1 diphenyl-2-picrylhydrazyl (DPPH), which was estimated photometrically. The effects of Gomishi or Shosaiko-to at concentrations of 10(-3) to 10(-5)g/ml on lipid peroxidation of rat brain homogenates were investigated. The lipid peroxidation was inhibited by the addition of these drugs, and the suppressive effect was also dependent on the concentration. These suppressive effects with Shosaiko-to were stronger than those of Gomishi. These results suggest that the radical trapping action of Gomishi or Shosaiko-to is the likely mechanism suppressing brain lipid peroxidation; Particularly, the suppressive effect on the brain's lipid peroxidation by Shosaiko-to is at least in part due to its radical trapping action and inhibition of O2-. production. PMID- 1446886 TI - [Effects of traditional Chinese medicines (dai-saiko-to, sho-saiko-to and hachimi zio-gan) on spontaneously diabetic rat (WBN/Kob) with experimentally induced lipid and mineral disorders]. AB - To clarify the therapeutic effects of several traditional Chinese medicines to improve disorders of carbohydrate, lipid and mineral metabolism, spontaneously diabetic rats (WBN/Kob) were treated with Vit. D2, 1 x 10(5) I.U./kg b.w./day, for 4 days, and then fed a hyperlipidemic diet containing traditional Chinese medicines for 6 weeks. The following results were obtained: 1) In the diabetic rats, the 3 traditional Chinese medicines further decreased the blood glucose level at 120 min after glucose loading in the glucose tolerance test. 2) The drugs increased the inorganic phosphate in the liver and normalized mineral metabolic disorder. 3) Hachimi-zio-gan decreased the cholesterol content in the kidney, and Sho-saiko-to decreased the cholesterol content in the elastin fraction (elastin-cholesterol) of the kidney. Such experimental results suggest that traditional Chinese medicines may be effective against the pathological conditions of diabetes mellitus that involve disorders of lipid and mineral metabolism. PMID- 1446887 TI - [Effects of sodium hyaluronate on the nociceptive response of rats with experimentally induced arthritis]. AB - Antinociceptive effects of sodium hyaluronate (Na-HA) were studied on the basis of improvement in the graded abnormal gait elicited by arthritis induced by intra articular administration of monosodium urate crystal (MSU) to rats. One hour before MSU injection, intra-articular administration of a 1.0% solution of Na-HA with different molecular weights, ranging from 4.70 x 10(5) to 2.02 x 10(6) (HA 200), improved the score of abnormal gait in a molecular weight-dependent manner in the experimental arthritis model. Similarly, administrations of HA-200 at concentrations ranging from 0.1 to 1.0% prior to MSU treatment resulted in improvement of the score in abnormal gait in a dose-dependent manner. To elucidate the antinociceptive mechanisms of Na-HA, effects of pretreatment with Na-HA (1.0%) of different molecular weights on prostaglandin E2 (PGE2) and bradykinin (BK) releases in synovial fluid 3 hr after MSU injection were studied. Increases in PGE2 and BK concentration in the synovial fluid were depressed in a molecular weight-dependent manner by Na-HA (1.0%) pretreatment. These results indicate that Na-HA attenuates the nociceptive responses inflicted by the MSU induced arthritis. Such an antinociceptive effect may be due to the inhibition of PGE2 and BK synthesis in the synovial joint of rats. PMID- 1446888 TI - A calcium-binding protein in bile and gallstones. AB - Calcium salts are often present in the center of all types of gallstones. Matrix proteins are known to be essential for biomineralization and may therefore also be important in the formation and growth of gallstones. Other researchers have described an anionic peptide fraction of a biliary lipoprotein complex in bile and a low-molecular weight acidic glycoprotein present in gallstones. Our goal was to determine whether such a protein was present in bile and whether this protein has any calcium-binding properties. We identified a pigment-associated, highly acidic protein that precipitates from bile on addition of CaCl2 0.5 mol/L. In addition, the protein is selectively concentrated in cholesterol and pigment stones. We have, therefore, confirmed the findings of these other researchers, and we have extended the study of this protein's interactions with calcium. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrates a single band (molecular weight < or = 14 kD) that reacts positively with cationic stains. The protein was shown to inhibit the precipitation of CaCO3 from a supersaturated solution. The capacity to bind calcium was further confirmed by autoradiography with 45Ca++ and by a membrane adsorption-binding assay. Calcium-induced aggregation was demonstrated by equilibrium dialysis and by quasielastic light scattering studies. Protein measured by Lowry's assay method and amino acid analysis constitutes only 2% to 4% of the harvested material. We speculate that a substantial lipid component may also be present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446889 TI - Hepatitis B virus precore mutants are identical in carriers from various ethnic origins and are associated with a range of liver disease severity. AB - Hepatitis B virus carriers in Israel are mostly HBeAg negative, of whom 5% to 10% have circulating hepatitis B virus. Recently, a hepatitis B virus variant with a stop codon in the precore region was identified, and it was suggested that specific mutations are associated with fulminant or severe chronic active hepatitis. We have analyzed serum samples from HBeAg-positive and HBeAg-negative patients by polymerase chain reaction, using primers spanning the precore/core region. Nucleotide sequence analysis (by direct sequencing) from amplified hepatitis B virus DNA demonstrated that viral genomes from all HBeAg-negative patients contain G to A mutation (nucleotide 1896), leading to the formation of a stop codon. An additional G to A mutation was identified three nucleotides downstream (nucleotide 1899). These patients are of various ethnic origins, with no unique clinical characteristics and with normal liver histology, chronic hepatitis or cirrhosis. No mutation at the precore/core region was observed in the HBeAg-positive patients. In conclusion, the precore mutations identified in hepatitis B virus carriers in Israel are identical regardless of the carrier's ethnic origin and are associated with mild-to-severe liver disease. PMID- 1446890 TI - Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients. AB - To determine the prevalence and natural history of gastric varices, we prospectively studied 568 patients (393 bleeders and 175 nonbleeders) with portal hypertension (cirrhosis in 301 patients, noncirrhotic portal fibrosis in 115 patients, extrahepatic portal vein obstruction in 117 patients and hepatic venous outflow obstruction in 35 patients). Primary (present at initial examination) gastric varices were seen in 114 (20%) patients; more were present in bleeders than in non-bleeders (27% vs. 4%, respectively; p < 0.001). Secondary (occurring after obliteration of esophageal varices) gastric varices developed in 33 (9%) patients during follow-up of 24.6 +/- 5.3 mo. Gastric varices (compared with esophageal varices) bled in significantly fewer patients (25% vs. 64%, respectively). Gastric varices had a lower bleeding risk factor than did esophageal varices (2.0 +/- 0.5 vs. 4.3 +/- 0.4, respectively) but bled more severely (4.8 +/- 0.6 vs. 2.9 +/- 0.3 transfusion units per patient, respectively). Once a varix bled, mortality was more likely (45%) in gastric varix patients. Gastric varices were classified as gastroesophageal or isolated gastric varices. Type 1 gastroesophageal varices (lesser curve varices) were the most common (75%). After obliteration of esophageal varices, type 1 gastroesophageal varices disappeared in 59% of patients and persisted in the remainder; bleeding from persistent gastroesophageal varices was more common than it was from gastroesophageal varices that were obliterated (28% vs. 2%, respectively; p < 0.001). Type 2 gastroesophageal varices, which extend to greater curvature, bled often (55%) and were associated with high mortality. Type 1 isolated gastric varices patients had only fundal varices, with a high (78%) incidence of bleeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446891 TI - The effect of oral-administered lactulose on colonic nitrogen metabolism and excretion. AB - The influence of lactulose on organic acid fermentation, nitrogen metabolism and excretion in the colon associated with its mechanism of action on hepatic encephalopathy was investigated. Orally administered lactulose in increasing amounts (0 to 20 to 40 to 80 to 160 gm/day) to 12 healthy volunteers decreased ammonia production in 16.6% fecal homogenates incubated 6 hr and 24 hr at 37 degrees C (mean +/- S.E.M.: from 7 +/- 1 to 0 +/- 0 and from 13 +/- 2 to 0 +/- 0 mmol/L, respectively). Every dose of lactulose was given for 3 days with intervals of 1 to 2 wk, and 24-hr stools were collected on day 3. Fecal concentrations of ammonia decreased (from 50 +/- 9 to 11 +/- 3 mmol/L), but ammonia excretions increased (from 6 +/- 2 to 17 +/- 4 mmol/24 hr). Total fecal concentrations of nitrogen decreased (from 1,043 +/- 78 to 300 +/- 136 mmol/L), but excretions of nitrogen increased fourfold (from 111 +/- 21 to 457 +/- 113 mmoL/24 hr) because of the increase in stool mass. Fecal pH declined (from 6.9 +/ 0.1 to 4.9 +/- 0.1), but total organic acids (short-chain fatty acids and DL lactate; range = 105 to 148 mmol/L) and osmolality in feces (417 to 450 mOsm/L) did not change, although the colonic fermentation of lactulose had a major impact on the proportions between the nontoxic acetate (increased from 65% +/- 2% to 89% +/- 3%) and the potentially neurotoxic 3-6-carbon fatty acids (decreased from 35% +/- 2% to 11% +/- 2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446892 TI - Pulmonary hemorrhage and glomerulonephritis in primary biliary cirrhosis. AB - We observed life-threatening intrapulmonary hemorrhages and focal proliferative glomerulonephritis in a 41-yr-old woman with primary biliary cirrhosis. The severity of the symptoms necessitated blood transfusions and mechanical ventilation; the patient improved with the help of corticosteroid therapy. No formal evidence of either Goodpasture's syndrome or any other well-defined systemic vasculitis could be found. Neutrophil cytoplasmic antibodies were initially positive and became undetectable after 3 mo of immunosuppressive treatment without relapse. This association has not been described previously and may be added to the list of extrahepatic immune-mediated conditions associated with primary biliary cirrhosis. PMID- 1446893 TI - Pallidal hyperintensity on magnetic resonance imaging in cirrhotic patients: clinical correlations. AB - Patients with cirrhosis show increased signal intensity in the globus pallidus on T1-weighted magnetic resonance imaging of the brain. This abnormal appearance of the basal ganglia has been related to the severity of liver failure and to the presence of portal-systemic shunting, although its cause and clinical significance remain unknown. We prospectively assessed the metabolic, neurological and neuropsychological statuses of 30 stable cirrhotic patients and correlated these clinical variables with computed measurements of globus pallidus signals. Some metabolic variables denoting disease severity appeared to be significantly related to image changes, although the strongest association was found with plasma ammonia levels. After adjustment for ammonia level, on multiple regression analysis, the other variables were not significant. Furthermore, pallidal changes were associated with specific neurological symptoms and neurological functions, symptoms and functions that also had a significant correlation with ammonia levels. Our findings suggest that globus pallidus signal abnormality could arise as a marker of brain impairment related to hyperammonemia. PMID- 1446894 TI - Variability of atrial natriuretic peptide plasma levels in ascitic cirrhotics: pathophysiological and clinical implications. AB - Ascitic cirrhotic patients are a heterogenous population with respect to factors that may affect plasma human atrial natriuretic peptide levels (such as degree of plasma volume and plasma levels of angiotensin II, vasopressin and norepinephrine). Thus the proven variability of plasma human atrial natriuretic peptide values in ascitic cirrhotic patients may be due also to the selection of patients, not only to the study conditions. The response to standardized stepped care medical treatment of ascites makes it possible to characterize ascitic cirrhotic patients with different patterns of renal sodium excretion, intrarenal sodium handling, plasma renin activity, plasma aldosterone and thus, probably, effective circulating volume. Consequently, we evaluated human atrial natriuretic peptide plasma levels in controls (n = 23), in ascitic cirrhotic patients who underwent spontaneous diuresis (group A, n = 7) and in cirrhotic patients who required diuretic treatment (group B, n = 44). The last group was then divided into two subgroups. Subgroup B-R (n = 25) included patients who responded to spironolactone alone, whereas subgroup B-NR (n = 19) included patients who did not respond to 500 mg/day spironolactone. All patients were maintained on identical normocaloric restricted sodium intake (80 mEq/day) throughout the study. Ascitic cirrhotic patients, as a whole, had higher values of human atrial natriuretic peptide than did controls (70.8 +/- 46.6 pg/ml vs. 41.7 +/- 16.3 pg/ml, p < 0.025). No difference was found in human atrial natriuretic peptide/plasma renin activity between the two groups (87 +/- 160 pg/ng/hr vs. 44 +/- 73 pg/ng/hr, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446896 TI - Hepatic mitochondrial glutathione depletion and progression of experimental alcoholic liver disease in rats. AB - Long-term ethanol feeding has been shown to selectively reduce hepatic mitochondrial glutathione content by impairing mitochondrial uptake of this thiol. In this study, we assessed the role of this defect in evolution of alcoholic liver disease by examining the mitochondrial glutathione pool and lipid peroxidation during progression of experimental alcoholic liver disease to centrilobular liver necrosis and fibrosis. Male Wistar rats were intragastrically infused with a high-fat diet plus ethanol for 3, 6 or 16 wk (the duration that resulted in induction of liver steatosis, necrosis and fibrosis, respectively). During this feeding period, the cytosolic pool of glutathione remained unchanged in the ethanol-fed animals compared with that in pair-fed controls. In contrast, the mitochondrial pool of glutathione selectively and progressively decreased in rats infused with ethanol for 3, 6 or 16 wk, by 39%, 61% and 85%, respectively. Renal mitochondrial glutathione level remained unaffected throughout the experiment. Serum ALT levels increased significantly in the ethanol-fed rats at 6 wk and remained elevated at 16 wk. In the mitochondria with severely depleted glutathione levels at 16 wk, enhanced lipid peroxidation was evidenced by increased malondialdehyde levels. Thus a progressive and selective depletion of mitochondrial glutathione is demonstrated in the liver in this experimental model of alcoholic liver disease and associated with mitochondrial lipid peroxidation and progression of liver damage. PMID- 1446897 TI - Liver regeneration and the effect of exogenous putrescine on regenerative activity after partial hepatectomy in cirrhotic rats. AB - There are conflicting data regarding the ability of the liver to regenerate after partial hepatectomy in animals and humans with cirrhosis. The purpose of this study was to document liver regeneration after partial hepatectomy in a carbon tetrachloride rat model of cirrhosis and to determine whether exogenous putrescine, a polyamine that has been reported to stimulate liver regeneration in animal models of acute liver failure, enhances regenerative activity in cirrhosis. Liver fibrosis and cirrhosis were produced by weekly intragastric gavage with carbon tetrachloride in 130 adult male rats. Vehicle-gavaged rats (n = 12) served as healthy controls. At surgery and at 4 and 8 hr after 70% hepatectomy, rats received normal saline solution or 1 or 10 mg/kg putrescine by intraperitoneal injection. Another group (n = 32) of carbon tetrachloride-treated rats was given putrescine (100 mg/kg) or normal saline solution twice daily for 10 days before partial hepatectomy and at 0, 4 and 8 hr after partial hepatectomy. Liver regeneration was documented 24 and 48 hr after partial hepatectomy on the basis of restitution of liver mass, ornithine decarboxylase activity and [3H]thymidine incorporation into liver DNA. Automated image analysis of the resected liver specimens separated carbon tetrachloride-treated rats into two subgroups: those with bridging fibrosis (fibrotic group) and those with micronodular cirrhosis (cirrhotic group). Restitution of liver mass and ornithine decarboxylase activity at 24 and 48 hr after partial hepatectomy were similar to carbon tetrachloride-treated rats (both fibrotic and cirrhotic) and vehicle treated healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446895 TI - Preformed lymphocytotoxic antibodies: the effects of class, titer and specificity on liver vs. heart allografts. AB - The effect on liver and heart allograft survival (ACI rats to Lewis rats) was studied after three methods of recipient presensitization and after different intervals between sensitization and transplantation. With comparable lymphocytotoxic antibody titers, liver allografts always survived longer than heart grafts. The titer, class and specificity of the antibodies varied with the method of sensitization. Four skin grafts produced IgG and IgM lymphocytotoxic antibody titers of 1:2,000 to 4,000. The IgG fraction was shown to have hepatic vascular endothelial specificity by indirect immunofluorescence. These primed recipients hyperacutely rejected both heart and liver allografts, which showed vascular deposition of IgG antibodies. Survival of either kind of graft was inversely proportional to the lymphocytotoxic antibody titer and length of time after placement of the last skin graft. Presensitization with a single heterotopic heart graft produced an even higher mixed IgG and IgM lymphocytotoxic antibody titer of 1:8,000 but with less IgG vascular endothelial specificity. These animals also hyperacutely rejected heart or liver grafts with tissue deposition of IgG but less consistently and with a weaker correlation with lymphocytotoxic antibody titers and time after sensitization. Sensitization with two pretransplant blood transfusions produced the lowest titer (1:500 to 1,000) and the least IgG vascular endothelial specificity. Liver allograft survival was routinely enhanced in these animals, and little effect was seen on heart grafts. Collectively, the experiments showed that the liver is not only resistant to antibody-mediated rejection relative to the heart but is more easily enhanced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446898 TI - Hemodynamic effects of calibrated stenosis of the superior mesenteric artery in conscious rats with portal vein stenosis. AB - Because superior mesenteric arterial blood flow is increased in portal hypertension and plays a role in elevated portal pressure, mechanical reduction of artery diameter should induce decreases in portal pressure and superior mesenteric arterial blood flow. In this study, calibrated superior mesenteric artery stenosis (induced with a 22-gauge needle) was performed in rats simultaneously with portal vein stenosis or 2 wk after creation of portal vein stenosis. Hemodynamic studies were performed 3 wk after induction of portal vein stenosis in conscious, unrestrained rats. At that time, neither weight loss nor digestive tract alterations were observed in rats with arterial stenosis. In neither group of rats with arterial stenosis was portal tributary blood flow significantly different from that of normal rats; nor was it significantly lower than in rats with portal vein stenosis without arterial stenosis. In both groups of rats with arterial stenosis, portal pressure was significantly lower (12.1 +/- 1.6 mm Hg and 12.5 +/- 1.8 mm Hg, respectively) than in rats subjected to portal vein stenosis (15.4 +/- 1.5 mm Hg) but significantly higher than in controls (7.2 +/- 1.0 mm Hg). In rats with arterial stenosis, cardiac index was also significantly lower than that in rats with portal vein stenosis but higher than that in controls. In conclusion, this study shows that both early and late superior mesenteric artery stenosis significantly reduce the degree of portal hypertension and the hyperkinetic state of rats with extrahepatic portal hypertension. Thus we can speculate that superior mesenteric artery stenosis might provide a new therapeutic approach for portal hypertension. PMID- 1446899 TI - Role of mesenchymal cell populations in porcine serum-induced rat liver fibrosis. AB - The role of liver mesenchymal cell populations in porcine serum-induced rat liver fibrosis were studied morphologically and immunohistochemically. Five-week-old rats were intraperitoneally injected with porcine serum twice a week and examined at various intervals between 3 and 24 wk after the initial injection. At an early phase, numbers of fibroblasts and extracellular matrix increased in the walls of central veins and in portal and capsular connective tissues. In the walls of central veins, the number of "second-layer cells" (i.e., the fibroblasts located at the second layer of the wall) increased. Connective tissue septa, accompanying some fibroblasts, extended from these interstitial tissues into the hepatic parenchyma, and their foremost edges came into direct contact with the perisinusoidal stellate cells. The sinusoids adjacent to the newly formed septa collapsed and later disappeared; this process resulted in the formation of hepatic limiting plates along the septa. At a more advanced stage, the interstitial fibroblasts and septal cells-which were derived from interstitial fibroblasts and the stellate cells-increased and became multilayered, constructing three-dimensional cell networks. These networks, together with increased collagen fibrils and elastic fibers, constitute the fibrotic dense connective tissue. In the control rat, smooth muscle cells were positive on vimentin, desmin and smooth muscle-alpha-actin staining. The stellate cells, second-layer cells, capsular and portal fibroblasts were shown to be vimentin and desmin positive and smooth muscle-alpha-actin negative. In the fibrotic liver, septal(fibroblastic) cells were vimentin and desmin positive and smooth muscle alpha-actin negative. We conclude that not only the perisinusoidal stellate cells but also the interstitial fibroblasts, including the second-layer cells, play substantial role in the development of porcine serum-induced septal fibrosis in rat liver. PMID- 1446900 TI - Resident mast cells are the main initiators of anaphylactic leukotriene production in the liver. AB - During anaphylaxis the sensitized liver can have substantial capacity for leukotriene production. However, the intrahepatic cellular source for these potent eicosanoid mediators has been unclear so far. We therefore analyzed the appropriate role of resident liver cells in organ-specific generation of leukotrienes by immunohistochemical localization of 5-lipoxygenase, by measurement of cysteinyl leukotriene production in animals or isolated livers and by histochemical monitoring of mast cells in rat, guinea pig and mouse livers, respectively. During anaphylaxis in vivo, these species all generated large amounts of leukotrienes. Immunohistochemistry with rat liver demonstrated resident mast cells as the predominant cell type in liver containing 5 lipoxygenase. Rat and guinea pig livers contained numerous mast cells and produced substantial amounts of leukotrienes on antigen challenge; in contrast, mouse livers neither showed detectable mast cells nor generated leukotrienes when stimulated analogously. Infusion of histamine or serotonin (1 mmol/L each) or of the degranulating substance P (8 mumol/L) did not elicit leukotriene generation in rat livers. Furthermore, substantial degranulation of liver mast cells by compound 48/80 (0.5 mg/kg body mass) was paralleled by only modest leukotriene formation (63 +/- 10 pmol in bile/kg body mass/30 min). These results indicate that during anaphylaxis mast cells are the main intrahepatic cells initiating leukotriene production and that such leukotriene generation is likely to be independent of mast cell degranulation or the release of histamine or serotonin. PMID- 1446902 TI - Does albumin regulate albumin? PMID- 1446901 TI - APF/CBP, an anionic polypeptide in bile and gallstones that may regulate calcium salt and cholesterol precipitation from bile. PMID- 1446903 TI - ADH1, 2 and 3: genes whose times have come. PMID- 1446904 TI - Thymic factor X treatment of chronic hepatitis B. PMID- 1446905 TI - United States' tort costs continue to escalate. AB - Tort costs in the United States totaled $132 billion in 1991, or 2.3% of the nation's total economic output; and medical malpractice accounted for $9.1 billion of that total, according to new data from Tillinghast, a division of Towers Perrin, New York City. PMID- 1446906 TI - Cancer at the crossroads. AB - A number of elements are transforming cancer care in hospitals. First is ongoing, rapid technological advance: Experts contend that biotechnology therapies will shift the site of cancer treatment from external, systemic treatments like radiation and chemotherapy, to targeted, tumor-specific drugs that boost the immune system. That change alone holds many implications for oncology management. In addition, an aging population, longer cancer survival rates, reimbursement concerns, and the increasing involvement of patients and their families in treatment decision making, will all have an impact on the way cancer care is designed and delivered. The time to plan, say experts, is now. Meanwhile, innovative treatment plans, patient care approaches, and collaborative efforts among institutions are moving hospital oncology into the 1990s in a dramatic way. PMID- 1446907 TI - Are trustees prepared to lead through health reform maze? AB - Not all hospital trustees realize the vital leadership role they must play as their hospitals move toward the future, say CEOs. As a result, executives understand that they have a major educative role to play in bringing their boards up to speed on health care reform issues--quickly. PMID- 1446908 TI - New AHA guidebook provides framework for implementing clinical practice guidelines. AB - A new guidebook from the AHA promises to help hospitals move from the abstract to day-to-day clinical practice when it comes to adopting clinical practice guidelines. At the same time, new federal guidelines offer another source from which hospitals can directly receive new information. PMID- 1446909 TI - Healthy investor interest in non-rated hospital bonds. AB - Despite persistent rumors of a "credit crunch," tax-exempt financing remains a viable source of capital for many hospitals that can't obtain investment-grade ratings. In fact, say experts, there's still strong investor interest in debt issued by lower-credit quality hospitals. PMID- 1446910 TI - CEOs link IS visions to hospital strategic plans. AB - More and more hospital CEOs are recognizing the importance of aligning the goals for their information systems with those of their strategic plans. In addition, information management experts offer advice on how CEOs can participate in IS selections without getting bogged down in details. PMID- 1446911 TI - Report outlines 'best practices' for surgery units. PMID- 1446912 TI - Survey shows gaps in competencies of new RNs. PMID- 1446913 TI - Malpractice risk the same for female and male ob/gyns. PMID- 1446914 TI - MD-directed critical pathways: it's time. PMID- 1446915 TI - Prolactin as an immunoregulatory hormone in mammals and birds. AB - The immunoregulatory function of prolactin (PRL) and the mechanism of its action in mammals seem to be well documented. Reciprocal interdependence between PRL secretion and immune system function is essential for normal ontogeny, development and aging. PRL receptors in lymphocytes participate in the transduction of its regulatory signal into the intracellular enzymatic machinery including that of the nucleus, leading to the expression of some genes and to the synthesis of new proteins. Activation of phosphoinositide turnover and subsequent increase in protein kinase-C activity seems to be a possible mechanism acting in the regulatory influence of PRL on mammalian immune cells. These cells in turn, under mitogen or antigen stimulation, secrete a substance with PRL-like activity. The regulatory function of PRL within the avian immune system is less well known, but it seems to have some features in common with those in mammals. Direct mitogenic action on thymocytes and splenocytes in the chicken might indicate the existence of PRL receptors in these cells and could explain the immunostimulatory effect of PRL observed in vivo, which is dependent on the time of hormone administration. As the avian PRL stimulates mitogenesis of rat Nb2 lymphoma cells, the mechanism of direct PRL action on immune cells in mammals and birds seems to be similar. PRL in chickens also modifies the level and the diurnal rhythm of corticosterone which, in turn, influences the immunoregulatory effect exerted by PRL. Thus, PRL seems to be an important factor, influencing directly or indirectly the avian immune system. PMID- 1446916 TI - Melatonin induced increase in gamma-interferon production by murine splenocytes. AB - Previously, we demonstrated that production of gamma-interferon (gamma-IFN) by the mouse splenocytes isolated at night was higher than from those isolated in the morning. In this paper we show that melatonin increased gamma-IFN production by murine splenocytes. Moreover, this stimulating effect was significantly higher (10 times) in the cells isolated at night than in those isolated in the morning (2 times). PMID- 1446917 TI - Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response. AB - We have treated 18 patients with metastatic malignant melanoma (MM) with high dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters. Two regimens differing in the sequence of treatment were employed, and 1-6 treatment cycles were given, depending on patient response. Two patients had a complete response (CR, 46+m, 14m), two patients a partial response (PR, 16m,6m), one a minimal response and four had a stable disease lasting 2-7 months, thus the response rate (CR+PR) was 22%. None of the following parameters, tested prior to initiation of the therapy and 1-2 days after termination of each course of IL-2, correlated with the clinical response: WBC counts (total and differential), levels of blood CD4 and CD8 T cells, NK cells, monocytes and B cells, production of IL-1 and IL-1 inhibitor by monocytes, responsiveness to 3 mitogens, NK/LAK cell activity, and serum levels of IL-1 alpha, IL-2, soluble IL 2 receptor, and TNF alpha. The only prognostic parameter was the greater increase in the level of IL-2 receptor (Tac)-bearing lymphocytes in the responding patients after 1-3 cycles of IL-2. The data suggests that non-specific immune parameters have no prognostic value for patients undergoing IL-2-based immunotherapy. PMID- 1446918 TI - Global degranulation of rat mast cells stimulated with DNP-polystyrene. AB - Mediator release was studied in rat peritoneal mast cells sensitized with a mouse monoclonal anti-DNP IgE antibody, and stimulated with DNP-ornithine covalently attached to radio-derivatized polystyrene petri dishes. Cells releasing serotonin at maximal rates were investigated by transmission electron microscopy. Generalized exocytosis of granules could be observed, suggesting non-directional release of mediators, and non-compartmentalized action of second messengers in mast cells stimulated with polystyrene-bound DNP. Stimulation of sensitized mast cells by DNP covalently bound to the rigid polystyrene surface is consistent with extrinsic mechanisms proposed for Fc(epsilon)RI receptor action, and suggests that internalization of Fc(epsilon)RI is not needed for triggering cell degranulation. PMID- 1446919 TI - Phagocytosis and microbicidal capacity of human monocytes in the course of HIV infection. AB - Phagocytosis and bactericidal activity of human monocytes were studied in asymptomatic HIV carriers and in patients with clinically apparent HIV infection, diagnosed as persistent generalised lymphadenopathy (PGL) or AIDS-related complex (ARC). Monocytes of asymptomatic HIV carriers manifested no significant changes while a decreased phagocytosis was shown by monocytes in the majority of patients with PGL or ARC. The latter patients also exhibited a decreased bactericidal activity of the cells. Tuftsin and even serum from healthy donors were found to normalise the disturbed monocyte function, the effect of tuftsin being more pronounced. Nevertheless, the examined sera contained neither factors which could stimulate nor factors which could inhibit phagocytosis. The obtained results indicated that the productive phase of HIV infection is associated with disturbed phagocytosis and disturbed microbicidal activity of monocytes, reflecting deficiency of serum factor(s) needed for the normal function of the cells. PMID- 1446920 TI - Degenerative changes in the A375 melanoma line induced by transforming growth factor beta 1. AB - A375 human melanoma cell cultures grown in the presence of TGF beta contained greatly reduced cell numbers and exhibited drastic alterations in cell morphology compared to the control cultures. Preincubation of the cells with the cytokine for only 18 h was sufficient to induce these changes irreversibly. Examination of TGF beta-treated cells in the electron microscope revealed large numbers of lipid filled vacuoles in the cytoplasm, greatly contracted nuclei and some loss of the otherwise abundant microvilli. Thus TGF beta may have a direct toxic effect on the A375 melanoma cells. PMID- 1446921 TI - Fast filtration enzyme immunoassay for haptens. AB - An immunometric method for determination of hapten concentration in fluids has been developed. High-affinity hapten-specific enzyme-labeled monoclonal antibodies are mixed with a sample containing hapten, then the mixture is filtered through a membrane with immobilized hapten. The level of enzyme activity retained by the membrane is inversely proportional to the concentration of hapten in a sample. The assay has been developed for theophylline, digoxin and phenobarbital. The coefficient of variation is less than 5% and the test takes about 2 min. PMID- 1446922 TI - Specific anti-A responses of SCID mice populated with human lymphoid cells from peripheral blood, umbilical cord, bone marrow and spleen after immunization with group A erythrocytes [corrected]. AB - Mice with severe combined immunodeficiency (SCID) were injected i.p. with 10 x 10(6) or 50 x 10(6) human leukocytes obtained from adult peripheral blood, umbilical cord blood, bone marrow and spleen from six group O individuals, together with allogeneic group A erythrocytes. Mice were bled every two weeks and levels of human IgG, IgM and anti-A were determined in the murine plasma. Spleen cells elicited the highest Ig levels (up to 5.2 mg/ml IgG) and umbilical cord the least (0-0.16 mg/ml IgG); maximum IgG levels were obtained at about 6-8 weeks after injection. Anti-A was detected in mice receiving adult peripheral blood or spleen leukocytes and immunizing erythrocytes 4-6 weeks after injection. Mice injected with the higher dose of leukocytes gave the best anti-A responses, but were more likely to develop tumours after 8 weeks. PMID- 1446923 TI - Tetrapeptide QDPR is a minimal immunodominant epitope within the preS2 domain of hepatitis B virus. AB - A hepatitis B virus preS2 deletion library with the preS2 sequence fused to the coat protein of the RNA phage fr (fr CP) as a carrier has been constructed and used for the approximate localization of epitope recognized by a panel of murine monoclonal anti-preS2 antibodies. DNA copies of putative preS2 epitopes were synthesized and cloned within the fr CP gene. Tetrapeptide Gln-Asp-Pro-Arg (QDPR) corresponding to the preS (132-135) sequence was found to be the minimal sufficient recognition site for one of the monoclonal antibodies, S26. The closely related tetrapeptide EDPR did not mimic the epitope activity of QDPR. PMID- 1446924 TI - Characterization of IgM molecules in light-chain deficient variants of a B-cell tumor. AB - Characterization of a membrane-IgM-negative variant cell line derived from the murine B-cell line 38C-13 revealed the absence of light chains and the presence of polypeptides with an apparent molecular size of 18 kDa and 14 kDa, previously denoted omega and iota and characteristic of pre-B cells. These polypeptides assemble with the mu chains into complexes with apparent molecular sizes of about 100 kDa and 200 kDa. It has been previously shown that light-chain-deficient variants of the 38C cell line undergo 'secondary' light chain rearrangements. It is suggested, therefore, that complexes of mu and the 'surrogate' light chains omega and iota play a role in this process. As these complexes do not reach the cell surface we would like to propose that the mechanism of secondary rearrangement is intracellularly controlled. PMID- 1446926 TI - Association of injury with neuropathic bone and joint disease. PMID- 1446925 TI - In vitro immune recognition of synthetic peptides from the Plasmodium falciparum CS protein by individuals naturally exposed to different sporozoite challenge. AB - The impact of duration and intensity of sporozoite challenge on the in vitro cell immune response to synthetic peptides of the circumsporozoite (CS) protein of Plasmodium falciparum was investigated in residents of a malaria endemic area in Burkina Faso (West Africa). Lymphocyte proliferation and interferon-gamma (IFN gamma) production were used to assess immune recognition of synthetic peptides corresponding to the polymorphic Th2R and Th3R regions, to the conserved CS.T3 sequence and to NANP and degenerate NVDP repeats. Immune responses were measured in adults and children from a village where they received more than 100 sporozoite inoculations per year and in adults living in a town, exposed to a 10 100 times lower challenge. A lifetime intense exposure apparently increased the ability to proliferate in response to most peptides in the rural adults, who all produced antibodies to NANP repeats. Surprisingly, cell cultures from these subjects seldom contained appreciable levels of IFN-gamma. In the urban adults, possibly due to the moderate challenge they are exposed to, significant differences in the proliferative potentials of the peptides could be detected. The highest stimulation indices were obtained with the genetically unrestricted CS.T3 peptide. Remarkably, proliferative responses to Th2R and Th3R appeared to be correlated with the humoral response to the CS protein, indicating a T helper significance of the epitopes. The differing proliferative potential of the polymorphic epitopes in the urban adults suggests that polymorphism might delay the development of immune responsiveness under conditions of sporadic transmission. The children from the highly malarious village displayed the lowest proliferative scores, accompanied by a high prevalence of antibodies to NANP repeats. On the basis of these findings, the hypothesis is proposed that a pure B cell reactivity to NANP repeats could ontogenetically precede the mounting of a conventional T-B cooperative immune response. PMID- 1446927 TI - Ipsilateral fractures of the femur and tibia. AB - From October 1987 to September 1990, 32 patients with ipsilateral fractures of the femur and the tibia were treated. There were 20 men and 12 women with a mean age of 27 years (range 18-75 years). All were caused by road accidents. There were 7 femoral and 22 tibial open fractures. The management of the fractures was partially the same. The tibial fractures were reduced and stabilized by a unilateral external fixator, while in 29 out of 32 femoral fractures, a closed intramedullary nailing was performed. The remaining three patients with an open grade III fracture were initially treated by external fixation, with two of them converted into nailing. The time of hospitalization ranged from 12 to 105 days (mean 30 days). The femoral fractures healed in an average of 15.5 weeks, while the tibial fractures healed in 18.5 weeks. The evaluation of our results was made according to Karlstrom and Olerud's criteria. We achieved 81 per cent excellent or good results and 19 per cent acceptable or poor, in a follow-up time of 19.5 months. PMID- 1446928 TI - The 'stove-in shoulder': results of treatment by early mobilization. AB - The 'stove-in shoulder' is an injury in which the scapula is fractured and the lateral fragments are displaced medially. Out of 10 patients, eight treated by early mobilization regained full shoulder function within 1 year. PMID- 1446929 TI - Resuscitation in northern Iraq. AB - The principles of Advanced Trauma Life Support (ATLS) were adopted by a Royal Navy surgical team deployed to northern Iraq. Over a 6-week period, 18 casualties of both military and civil trauma required active resuscitation, 10 being under the age of 16 years. Triage of multiple casualties was necessary on three occasions. Two patients died. It was difficult to exclude cervical spine injury. Venous cut-down was frequently unsuccessful, so that internal jugular vein cannulation was life-saving. Crystalloid was used as the primary infusion without apparent disadvantage. Cross-matched blood was unavailable and one patient died with haemolysis after massive transfusion. Hypothermia was a problem despite the high environmental temperature. Laboratory and radiological facilities were extremely limited. Non-medical staff were trained most effectively to assess vital signs, although sophisticated monitors became available. These problems are discussed and compared with previous experience. Recommendations are made to improve future outcome. PMID- 1446930 TI - The use of power tools in the insertion of cortical bone screws. AB - Cortical bone screws are commonly used in fracture surgery, most patterns are non self-tapping and require a thread to be pre-cut. This is traditionally performed using hand tools rather than their powered counterparts. Reasons given usually imply that power tools are more dangerous and cut a less precise thread, but there is no evidence to support this supposition. A series of experiments has been performed which show that the thread pattern cut with either method is identical and that over-penetration with the powered tap is easy to control. The conclusion reached is that both methods produce consistently reliable results but use of power tools is much faster. PMID- 1446931 TI - Management of childhood femoral neck fractures. AB - Forty-three children with displaced transcervical femoral fractures were reviewed at a mean follow-up of 7.2 years and results were assessed using Ratliff's criteria. Of 22 patients treated by internal fixation alone, 10 had good, 6 had fair and 6 had poor results. The results in 21 children treated by internal fixation along with primary transverse intertrochanteric undisplaced osteotomy were: 14 good, 5 fair and 2 poor, but none improved to a statistically significant level (P = 0.139). However, the osteotomy improved the fracture union significantly and no delayed union or non-union was noted in this group (P = 0.05). There were no complications related to the osteotomy itself. PMID- 1446932 TI - The importance of clinical details when reporting accident and emergency radiographs. AB - The effect of clinical information on the accuracy of reporting accident and emergency (A&E) radiographs was studied in two A&E officers and five radiologists involved in their daily reporting. Each was shown 50 sets of radiographs, 30 subtle fractures and 20 controls. In one half the clinical history and precise localization was provided, and in the other half no such information was given. After an interval of 6 months the radiographs were viewed again with the amount of information reversed. The observers were asked to determine the presence of injury, describe its site, and indicate how sure they were of their diagnosis. Correct diagnosis was improved from 72.3 per cent to 80.3 per cent overall, and from 68.1 per cent to 81.4 per cent in the fracture group. All observers improved their performance with clinical details. The results confirm that accurate clinical details improve injury location. PMID- 1446933 TI - The dynamic ASIF-BM tubular external fixator in the treatment of open fractures of the shaft of the tibia. AB - The dynamic ASIF-BM external fixator incorporates telescopic tubes for axial dynamization and angled bayonet screws to keep the tubes parallel to the bone axis, that is essential for gliding, and adjustment of rotation. The results after treatment of 70 type II and III open tibial fractures with static ASIF and dynamic ASIF-BM frames were analysed. Of the fractures, 32 were treated with the delta ASIF static frame, the other 38 with delta and uniplanar dynamic ASIF-BM frames. The groups were found to be comparable. The results of the study confirm that tubular external fixation is a safe method for treating the bone and soft tissue lesions in such fractures. The comparative study shows that axial compression, using the ASIF-BM device, with early weight bearing, gave a higher rate of union (97 per cent against 87 per cent with the ASIF frame), a shorter healing time (19 weeks against 29 weeks with the ASIF frame) and a decreased need for bone grafting (21 per cent against 84 per cent with the ASIF frame). The incidence of pin track infection was also decreased in dynamic frames. Thus it seems that the ASIF-BM dynamic fixator has a valuable part to play as a definitive mode of therapy for severe open fractures of the tibial shaft. PMID- 1446934 TI - A study of diaphyseal fracture repair using tissue isolation techniques. AB - The repair of an osteotomy of the rabbit tibia was studied by arterial radiography and by histology following selective isolation of the potential sources of the fracture callus. The periosteum was isolated by reaming and nailing the medullary cavity and the bone marrow was isolated by applying a Silastic sheath around the shaft. The results revealed certain features of periosteal and medullary healing. PMID- 1446935 TI - Death in hospital after head injury without transfer to a neurosurgical unit: who, when, and why? AB - Most studies of hospital deaths after head injury have been in patients transferred to neurosurgical units (NSU), but over 90 per cent of hospitalized head-injured patients are not transferred and some of these die. To assess the effectiveness of triage of seriously head-injured patients in Glasgow, we studied 270 patients who died after head injury in any of the six Glasgow general hospitals during 1979-1988 and who were not transferred to the regional NSU. The proportion of fatal cases of head injury who had not been to the NSU fell from 69 per cent in 1971-1975 to 45 per cent in 1979-1988. Most of the untransferred patients were elderly, and most died from irremediable injuries or complications. Although 31 (11 per cent) had a significant intracranial haematoma, only seven of these might have been salvaged by neurosurgical intervention. Seven other patients died from potentially preventable extracranial injuries or complications. These findings suggest that a relatively satisfactory level of triage of seriously head-injured patients has been achieved, by promoting effective communication between neurosurgeons and other specialists, and by a continuous programme of audit and education. PMID- 1446936 TI - Paraplegia and traumatic rupture of the aorta: a disease process or surgical complication? AB - Surgical repair of traumatic rupture of the aorta results in an excellent survival rate especially among the young, although paraplegia continues to be a serious postoperative complication. The authors present nine cases admitted to Stoke Mandeville Hospital, England, including detailed post-mortem findings on one of the cases. Although it was difficult to be certain of the patients' general and neurological status prior to surgery, as it was not well documented in the patients' case notes, it was evident that systemic hypotension and poor distal aortic perfusion were responsible for the disabling complication. A review of the initial medical management of these patients and the surgical techniques employed in repairing such injuries is urgently needed. PMID- 1446937 TI - Anterior dislocation of the shoulder: a simple method of reduction. AB - An effective method for reducing anterior dislocation of the glenohumeral joint which does not require either sedation or traction is described. The patient performs the manoeuvre. A series of 32 consecutive patients were treated by this method. Easy reduction was achieved in 72 per cent, with no complications and patients spent less than half as long in the accident and emergency department as when it is not successful. We recommend this simple technique as a first method of reduction in patients presenting to accident and emergency departments. PMID- 1446938 TI - A gentle method of reducing traumatic dislocation of the hip. PMID- 1446939 TI - Serum c-reactive protein in patients with serious trauma. AB - Daily serum c-reactive protein (CRP) concentration was monitored in 98 patients (26 female) admitted to the Major Injuries Unit (MIU) at Birmingham Accident Hospital following serious trauma. The mean (SD) increase in CRP concentration for 79 survivors and 19 non-survivors between days 1 and 2 after trauma were 69.5 (74.6) and 111.8 (59.0) mg/l/24 h, respectively (P = < 0.001). By day 4 after trauma the mean serum CRP concentrations for survivors and non-survivors were 150.9 (76.9) and 233.4 (100.8) mg/l (P < 0.001), respectively. Injury severity data were available for 50 patients. The mean (range) injury severity score was 25.2 (4-50), Glasgow coma scale 10.4 (3-15), revised trauma score 6.5 (3.39-7.8) and predicted survival 0.78 (0.02-0.99). Univariate regression analysis of serum CRP on days 1-5 after injury against revised trauma score and injury severity score, revealed an inverse correlation between day 1 serum CRP and Glasgow Coma Score (r = -0.306, P < 0.05), but no correlation with injury severity score or predicted survival on any of the study days. The lack of correlation between serum CRP and injury severity or predicted survival, and the strong association with actual survival, suggests that the acute inflammatory response to serious trauma and subsequent complications, is an important determinant of outcome. PMID- 1446940 TI - Small intestinal perforation following minor trauma. AB - Small intestinal perforation occurred in two patients aged 70 years and 88 years who had experienced minor trauma by tripping or falling on the pavement. They both developed signs of generalized peritonitis and at laparotomy were found to have perforated the mid ileum. There was no sign of direct abdominal trauma but they had suffered minor facial trauma as a result of the fall. PMID- 1446941 TI - Correlation between injury severity scores and subjective ratings of injury severity: a basis for trauma audit. AB - A retrospective review of 1900 road accident victims attending the emergency departments of two Melbourne hospitals was undertaken to identify Injury Severity Score levels which could distinguish between minor, moderate, severe and critical injury. Injuries scoring ISS 6 or below were designated 'minor' because they were associated with a low risk of requiring admission to hospital. Case notes of patients scoring above ISS 6 were then reviewed by a panel of clinicians, who independently rated each patient's overall injury severity as moderate, severe or critical according to what was recorded in the notes and their 'clinical' judgement. ISS values were compared with clinicians' ratings. Measures of each clinician's individual rating consistency, and correlation between pairs of clinicians with respect to inter-rater consistency, were made. By combining data from both hospitals it emerged that 'moderate' injury corresponded to ISS 8-13, 'severe' to ISS 14-20 and 'critical' to ISS 21 and above. These ISS breakpoints will be useful in selecting groups of injured patients for future trauma audit studies. PMID- 1446942 TI - Cracking of the femoral shaft by the gamma nail. PMID- 1446943 TI - The cost of home delivery. PMID- 1446944 TI - Ruptured calcified tendo Achilles: successful non-operative treatment. PMID- 1446945 TI - 'Quadriplane' fracture of the distal tibia: a triplane fracture with a double metaphyseal fragment. PMID- 1446946 TI - Mountain bike injury to the abdomen, transection of the pancreas and small bowel evisceration. PMID- 1446947 TI - An irreducible medial cuneiform fracture-dislocation. PMID- 1446948 TI - Magnetic resonance imaging of AO/ASIF stainless steel and titanium implants. PMID- 1446949 TI - Drill bit failure with implant involvement--an intraoperative complication in orthopaedic surgery. AB - This paper aims to investigate whether drill bit fragments which are in contact with an implant behave differently to those without contact to the implant and if so in what way. There is particular emphasis on whether two metals in contact are subject to corrosion and whether the products of such a corrosion lead to undesirable tissue reactions. The orthopaedic surgeon must know whether a drill bit fragment should be removed if it is in contact with an implant, in particular, whether there will be negative consequences for the tissue if it is left in the body. It is necessary to establish how much additional trauma is justified in removing a broken fragment and how the surgeon can determine intraoperatively whether there is contact between the fragment and the implant. Finally, this investigation aims to establish whether the fragment can be left in the body until implant removal or whether it can be left permanently in situ. PMID- 1446950 TI - Magnetic resonance of the musculoskeletal system. PMID- 1446951 TI - Quantitative computed tomography: from linear absorption coefficients to bone mass. PMID- 1446952 TI - Drill bit failure without implant involvement--an intraoperative complication in orthopaedic surgery. AB - The aetiology, frequency and consequences of drill bit failure during surgical intervention in human and animal bone tissue are investigated and discussed to provide the surgeon confronted with this problem with a scientifically based procedure. The literature on this subject is rather inadequate, i.e. only one publication in the last decade could be found dealing with this topic and this was a veterinary case. The Laboratory for Experimental Surgery in Davos has received several enquiries from the medical profession worldwide as to correct procedure in the case of drill bit failure. Three sources of information were investigated in order to furbish a reply to these enquiries, these were the AO/ASIF documentation centre in Berne, a survey of 280 surgeons and orthopedic doctors in Switzerland and a survey of 83 AO/ASIF foundation members. One broken tap (tool steel) was removed two years after the operation and metallographic investigations carried out. A frequency of 3 drill bit failure per 1000 internal fixations (0.3%) is apparent in nearly all data. The reasons for drill bit failure were investigated. Drill bit failure occurs more frequently in the proximal femur and when using angled plates. On the basis of this enquiry the following guidelines can be offered to the surgeon. A broken drill bit which is not in contact with an implant can be left in the body without any risk of delayed recovery. However, if the drill fragment is situated near a joint or if it can be easily removed without further trauma to the bone, then it should be removed. Once the fracture has healed the broken drill bit should be removed along with the implant provided no exceptional difficulties are involved. PMID- 1446953 TI - Creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) activity in serum before and after intravenous salbutamol administration of patients with bronchial asthma. AB - The effect of salbutamol, a selective beta 2-adrenergic agonist, on creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) activity in serum of 20 asthmatic patients was investigated. Venous blood was obtained 30 min, 2 h and 4 h after 0.5 mg salbutamol intravenous injection of 0.5 mg salbutamol. Total creatine kinase activity was assayed on a Technico RA-1000 analyzer with the IFCC recommended method. CK-MB activity was determined using a centrifugal analyzer (Cobas Fera, Roche, Switzerland). Reagent kits were provided by Boehringer Mannheim (FRG). We observed no increase of CK-activity after salbutamol, and found a statistically significant increase of CK-MB activity. Serum CK-MB activity before treatment was 13 +/- 10/IU/l after 30 minutes drug, 31.8 +/- 19 IU/l after 2 h 27.2 +/- 17.79 and after 4 h 22.6 +/- 12 IU/l. We conclude that salbutamol exerts a cardiotoxic effect. PMID- 1446954 TI - Tissue reaction after intramuscular injection of liposomes in mice. AB - Liposomes are effective carrier systems for prolonged drug release. As all other drug formulations for parenteral use, the safety of liposomal formulations should be established before clinical application. In this study, some safety aspects of intramuscularly injected (single dose) "gel-state" type liposomes and the ability of liposome encapsulation to diminish irritating effects of intramuscularly applied drugs were studied by histopathological analysis over a period of 14 days in mice. Injection of saline solution showed no tissue reaction at the injection site. Intramuscular injection of liposomes alone showed an infiltrative reaction consisting of a population of macrophages. Within this population fat cells were present. In time, the population of macrophages present at the injection site was largely replaced by loose connective tissue. Novaminsulfon (NS) injected intramuscularly in "free" form is a strongly irritating drug, causing hemorrhage, cell necrosis, inflammatory reactions and eventually fibrosis. However, NS being encapsulated in liposomes was hardly more irritating than liposomes alone. The same was true for liposome-encapsulated chloroquine and free chloroquine. When sustained-release of a drug is therapeutically desirable, the parenteral application of a liposome-encapsulated formulation can be considered for drugs, in particular for those drugs causing tissue injury at the injection site. PMID- 1446955 TI - A correlation between digoxin plasma concentrations and systolic time intervals in hospitalized congestive heart failure patients. AB - Plasma digoxin level is at best an indirect measure of pharmacological response to digoxin in patients being treated for congestive heart failure. Systolic time interval (STI) measurement reflecting left ventricular function at the physiological site of action of digoxin, is both more direct and non-invasive. With a portable instrument to measure systolic time intervals, the measurement can also be convenient for hospital staff. A portable electrocardiogram (ECG) machine was modified to mimic the capabilities of a large, multichannel model. Upon satisfactory evaluation, it was employed in the collection of systolic time interval data from five hospitalized patients undergoing digoxin treatment. An attempt was made to show a relationship between STI indices and digoxin plasma concentrations. Additionally, a statistical comparison was made of change in STI (delta STI) and plasma digoxin concentration both before and after drug administrations. The change in pre-ejection period (delta PEP) values show a significant difference over the changes in total electromechanical systole (delta QS2) and the changes in left ventricular ejection time (delta LVET). In three congestive heart failure patients, the time course of the change in plasma concentration showed good correspondence with delta PEP. PMID- 1446956 TI - Failure of predicted creatinine clearance equations in HIV-seropositive patients. AB - The Cockcroft and Gault (CG) [1976] method of predicted creatinine clearances (CCR) accurately predicts measured 24-hour CCR values in healthy volunteers. The present study compared the relationship between measured and predicted CCR through 5 methods: CG, J1 [Jelliffe 1971], J2 [Jelliffe 1973], M [Mawer et al. 1972], and H [Hull et al. 1981], in 42 HIV-seropositive patients: 21 ARC/21 AIDS, 35M/7F, 26 homosexual/16 intravenous drug users, age: 37 +/- 7 years, actual body weight: 74 +/- 14 kg, CD4: 0.286 +/- 0.185 x 10(9) cells per liter (mean +/- SD). Measured CCR values poorly correlated with serum creatinine levels (r = -0.35; p < 0.01). The average measured CCR was 106 +/- 29 ml/min compared with 94 +/- 21 (CG; r = 0.49), 78 +/- 13 (J1; r = 0.41), 77 +/- 14 (J2; r = 0.44), 97 +/- 21 (M; r = 0.51) and 95 +/- 17 ml/min (H; r = 0.32). Standardization to body surface area or lean body weight or stratification by patient factors (gender, disease stage, risk factors, drug treatment) did not improve correlations. However, patients with normal microalbumin excretion rates had more predictable CCR values compared with those who had excess excretion, suggesting the influence of HIV associated nephropathy on CCR estimation. Since all predicted CCR equations consistently underestimated actual values, these equations should be used with caution in estimating measured CCR in HIV-seropositive patients. PMID- 1446957 TI - Morning vs evening effects of intrapulmonary administration of heparin in healthy men. AB - Calcium heparin in a dose of 13,200-15,300 U was administered in 8 healthy men, aged 26-54, by inhalation at 8:00 or 20:00, where each study was separated by a minimum of three weeks interval. Serum coagulation variables, lipids, electrolytes and enzymes were measured before inhalation, 2 h later and after 48 h. Following heparin inhalation changes both in coagulation variables and less distinct in lipids variables were noted at both test times, but no morning evening differences were observed, with the exception of cholesterol and HDL. PMID- 1446958 TI - Clinical effect of indolidan in congestive heart failure. AB - Indolidan (IN) experimentally inhibits type IV phosphodiesterase. It was administered to twelve patients (age 64 +/- 15 years) with New York Heart Association (NYHA) class 2-3 congestive heart failure in which digoxin and diuretic therapy were continued. IN was administered i.v. at 1,180 +/- 340 micrograms (15 micrograms/kg) over two hours. After 24 hours, IN was given p.o. at 231 +/- 44 micrograms. The time course effect of IN i.v. revealed an increase in cardiac index and a decrease in pulmonary capillary wedge pressure and blood pressure. Daily oral administration of IN or placebo was carried out for up to 3 months. There were no significant hemodynamic changes of chronically administered IN. The maximum oxygen uptake increased in placebo relative to IN therapy. IN tended to be arrhythmogenic as evidenced by a general increased frequency of ventricular premature contractions of both single and paired type. Therefore, IN had some hemodynamic efficacy on acute i.v. and p.o. administration but not during chronic therapy, and there was negative safety features of arrhythmias. PMID- 1446959 TI - Investigation of the bioequivalence of two carbamazepine sustained-release formulations in healthy subjects. AB - A bioavailability study of two commercial carbamazepine sustained-release formulations was carried out in 14 healthy male subjects in order to compare plasma concentration/time profiles and to determine the relative bioavailability of carbamazepine (CBZ). This randomized study had a single-dose, crossover design and consisted of two trial periods separated by a three-week wash-out period. A sensitive, validated HPLC method was used to analyze plasma carbamazepine levels. Bioequivalence was only accepted for the test (Timonil 600 retard from Desitin Arzneimittel GmbH) and reference preparations (T and R) if the 90% confidence interval (parametric or non-parametric) for the ratios of the median values of the target variables was completely within the bioequivalence range. The following values were found for relative bioavailability: T/R: AUC = 109.6 (101.5 116.5)%, MRT = 96.4 (92.0-100.4)%, HVD = 92.4 (85.0-97.8)%. Applied to these pharmacokinetic data, the requirements for bioequivalence are met when the inclusion rule is used. PMID- 1446960 TI - Psychotherapy and addiction: a survey of journals. AB - A content analysis was done on 1,239 articles published from 1984 to 1987 in seven leading alcohol and addiction journals to ascertain the frequency of articles on psychotherapeutic treatment published relative to other treatments for alcohol and drug dependence. Therapeutic intervention articles account for less than 10% and psychotherapy treatment articles for less than 3% of the articles analyzed. Postulations such as the effects of a prevailing acceptance of the disease model to level of practitioner sophistication are made about this relatively small number. Nontherapeutic treatment articles are classified according to research methodology. Suggestions for research are made. PMID- 1446961 TI - Profiles of alcoholics according to the SCL-90-R: a confirmative study. AB - The Symptom Checklist-90-Revised (SCL-90-R) has often been used in studies of alcoholic populations. Based on findings reported in the literature and data gathered on 712 alcoholics in treatment, this paper investigates the general trends in the responses of alcoholics to the SCL-90-R. On global measures as well as on each of the symptom scales, the scores of alcoholic groups reveal a symptomatology two to five times as severe as that observed in the general population. The Psychoticism dimension shows the most marked divergence with the general population. In almost each of the study groups, the Depression Scale registers the highest scores, followed by Obsessive-Compulsive, Interpersonal Sensitivity, and Anxiety. PMID- 1446962 TI - Substance use/misuse among female prostitutes and female arrestees. AB - The literature has documented the correlation between prostitution and drug use/misuse. This study probed demographics, drug use experimentation and frequency, age of first drug use, and drug use treatment among 53 female prostitutes and 47 female arrestees. The results indicated that: 1) prostitutes were likely to drop out of school; 2) significantly more prostitutes had tried drugs, had used drugs with greater frequency and had begun drug/alcohol use at younger ages. These results imply that: 1) early drug/alcohol use and withdrawal from school could leave young women vulnerable and at higher risk of becoming involved in prostitution; and 2) drug use treatment and intervention needs to begin at younger ages. PMID- 1446963 TI - Symptom reduction and sobriety in the male alcoholic. AB - The relationship between subjective symptom reduction and sobriety was studied for 82 male alcoholics who had completed an inpatient Alcoholic Rehabilitation Unit that included six or more biofeedback/relaxation sessions. Specific symptom relief for anxiety was significantly correlated with sobriety. In addition, the reduction of symptoms showed a positive trend with sobriety. The discussion focuses on the relationship of anxiety-related symptoms and alcohol abuse. PMID- 1446964 TI - The age of alcohol onset and alcohol, cigarette, and marijuana use patterns: an analysis of drug use progression of young adults in New York State. AB - The authors extend the gateway theory by examining the relationship between the onset age of alcohol and the progression of drug use (alcohol, cigarettes, and marijuana) among 16 to 24 year old young adults residing in New York State. Logit analysis is employed to estimate the impact of the early onset of alcohol use on the subsequent use of other drugs. The findings suggest that alcohol use increases the chance of using cigarettes and marijuana, and alcohol-cigarette use significantly increases the likelihood of using marijuana. The early onset of alcohol use affects the current use of alcohol and other drugs; the impact is the strongest when the onset is initiated in a posited critical age period between 13 and 16. PMID- 1446965 TI - Sexual dysfunction and psychological distress in methadone maintenance. AB - We administered the Derogatis Sexual Functioning Inventory to 25 methadone maintenance patients who had been on a stable dose of methadone for at least 2 months, and obtained ratings of depression and anxiety, levels of sex hormones, and liver function tests. Five subjects with significantly lower Global Sexual Satisfaction Index scores (p < .0001) had more psychological symptoms, higher methadone doses, poorer body image, and less sexual drive and satisfaction, but normal fund of sexual information and lifetime experience. Sexual dysfunction among methadone maintenance patients may be due to coexisting psychiatric problems rather than caused by opiates. Methadone patients presenting with sexual dysfunction should receive psychiatric evaluation. PMID- 1446966 TI - Effect of alkylation with different sized substituents on thermal stability of lysozyme. AB - The amino groups of hen egg white lysozyme were reductively alkylated by the reaction with aliphatic aldehydes of various chain lengths and with two aldehydes of different steric hindrance at pH 7.5 and 4 degrees for 3 h. About four of the original six lysine residues were modified by the reaction with acetaldehyde, n butylaldehyde or n-hexylaldehyde. About three lysine residues were 2,2 dimethylpropylated with trimethylacetaldehyde while a single residue was modified with benzaldehyde. The thermal stabilities of these alkylated lysozymes were investigated by differential scanning calorimetry (DSC) at different acidic pH values. Alkylation thermally destabilized the proteins, depending not only on the extent of modification but also on the size of the substituent. The alkylated derivatives were 8-19 kJ/mol less stable than native lysozyme at 25 degrees and pH 3.0. The temperature dependences of the activities of the alkylated lysozymes against ethylene glycol chitin indicated that the orders of the optimum temperatures and the maximum activities were exactly the same as the order of the thermal stabilities. PMID- 1446967 TI - Hydrolysis of peptide esters by different enzymes. AB - The combined use in peptide synthesis of the Fmoc-group with methyl, benzyl or p nitro benzyl esters is not practical because of the elimination of the Fmoc-group under basic conditions and by catalytic hydrogenation. Nevertheless the solution synthesis of peptides requires those combinations in some cases. For this purpose we have investigated enzymatic hydrolysis of some tri and tetrapeptide esters. The hydrolysis were carried out under pH-control. We measured deprotection of the carboxyl group by thermitase, porcine liver esterase, carboxypeptidase A and alpha-chymotrypsin. The main problems are to suppress proteolytic degradation of the peptide bond and to bring the protected peptides into solution. To solve both problems we used dimethylformamide and dimethylsulfoxide as cosolvents. The ratios between esterolytic and proteolytic activity were estimated under various cosolvent concentrations. Advantages of this method are to avoid side reactions of alkaline instable side chains (e.g. asparagine, glutamine), cleavage of base labile protecting groups and racemization by alkaline saponification. The enzymatic deprotection was followed by HPLC, HPTLC and titration. On a preparative scale this method gives good yields and sufficiently pure products. PMID- 1446968 TI - Unexpected racemization of proline or hydroxy-proline phenacyl ester during coupling reactions with Boc-amino acids. AB - When L-proline or O-benzyl-trans-4-hydroxy-L-proline phenacyl ester was coupled with Boc-amino acids in dimethylformamide using water-soluble carbodiimide (WSCI) in the presence of anhydrous 1-hydroxybenzotriazole (HOBt) as coupling reagents, extensive racemization was observed at the C alpha of the proline or hydroxy proline residue. The extent of racemization was measured by HPLC after the coupling with Boc-L-Leu-OH in the presence or absence of HOBt. The extent of racemization increased when HOBt was added to the reaction mixture, but greatly decreased when it was not, indicating that HOBt was needed for inducing racemization. Almost no racemization was observed when the coupling reaction was carried out by the mixed anhydride procedure in tetrahydrofuran or by the carbodiimide method in dichloromethane without using HOBt. In the case of coupling reactions with ordinary L-amino acid phenacyl esters, no racemization was observed. Examination of some model systems yielded sufficient evidence to prove that HOBt is an efficient catalyst for racemizing proline or hydroxy proline phenacyl ester not only in the stage of cyclic intermediate formation but also in the opening of the ring structure. Thus, the racemization reaction was found to be closely related to the formation of the cyclic carbinol-amine derivative. PMID- 1446969 TI - Synthesis of optically pure C alpha-methyl-arginine. AB - Optically pure L-(+)-C alpha-methyl-arginine and D-(-)-C alpha-methyl-arginine were synthesized. Experimental results indicated that DL-C alpha-methyl-arginine methyl ester could be resolved by trypsin, but workup posed a technical difficulty. Chemical resolution at the stage of DL-C alpha-methyl-ornithine, followed by selective guanidination using N,N'-di-Cbz-S-methylisothiourea and hydrogenolysis provided a effective and practical method for the synthesis of optically pure C alpha-methyl-arginine. PMID- 1446970 TI - Predicted secondary structure of bovine prothrombin fragment 1 and related proteins in different environments by circular dichroism spectroscopy. AB - Circular dichroism spectroscopy was used to investigate the structure of bovine prothrombin fragment 1 (BF1) and related proteins in several environments. The conformational change induced in BF1 by the addition of Mg[II] ions was found to be different from that induced by Ca[II] or Sr[II]. The Ca[II] and Sr[II] conformations appear to differ only slightly from the apo-metal conformation. The conformation of the 1-45 fragment of prothrombin, however, is markedly different than the conformation of the same fragment in the presence of either Ca[II] of Mg[II]; both of the latter structures differ substantially from one another. The presence of phospholipids has almost no effect on the structure of either BF1 or the 1-45 fragment; in the presence of both phospholipids and Ca[II] a structural change is seen for the 1-45 fragment but not BF1 (relative to the protein alone). The addition of phospholipids to the Mg[II]/BF1 structure did not induce a CD detectable conformational change, while the addition of phospholipids to the Ca[II]/BF1 or Sr[II]/BF1 structures induced a change to a conformation similar in secondary structure composition to the relative apometal structures. PMID- 1446971 TI - Conformationally biased analogs of oxytocin. AB - Four diastereomeric analogs of oxytocin containing substituted phenylalanine in position 2 were synthesized. This modified phenylalanine side chain contained one methyl group attached to the beta-carbon and the second one at the 2' position of the aromatic ring. All analogs were found to be inhibitors of uterotonic activity of oxytocin with pA2 values ranging from 6.0 to 8.3; the most potent one (pA2 = 8.3) contained dimethylphenylalanine of the D-erythro configuration. PMID- 1446972 TI - Design of potent substrate-analogue inhibitors of canine renin. AB - Through a systematic study of structure-activity relationships, we designed potent renin inhibitors for use in dog models. In assays against dog plasma renin at neutral pH, we found that, as in previous studies of rat renin inhibitors, the structure at the P2 position appears to be important for potency. The substitution of Val for His at this position increases potency by one order of magnitude. At the P3 position, potency appears to depend on a hydrophobic side chain that does not necessarily have to be aromatic. Our results also support the approach of optimizing potency in a renin inhibitor by introducing a moiety that promotes aqueous solubility (an amino group) at the C-terminus of the substrate analogue. In the design of potent dog plasma renin inhibitors, the influence of the transition-state residue 4(S)-amino-3(S)-hydroxy-5-cyclohexylpentanoic acid (ACHPA)-commonly used as a substitute for the scissile-bond dipeptide to boost potency-is not obvious, and appears to be sequence dependent. The canine renin inhibitor Ac-paF-Pro-Phe-Val-statine-Leu-Phe-paF-NH2 (compound 15; IC50 of 1.7 nM against dog plasma renin at pH 7.4; statine, 4(S)-amino-3(S)-hydroxy-6 methylheptanoic acid; paF, para-aminophenylalanine) had a potent hypotensive effect when infused intravenously into conscious, sodium-depleted, normotensive dogs. Also, compound 15 concurrently inhibited plasma renin activity and had a profound diuretic effect. PMID- 1446973 TI - Efficient solution-phase synthesis of multiple O-phosphoseryl-containing peptides related to casein and statherin. AB - The multiple Ser(P)-containing peptides, H-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA, H-Asp-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA and H-Glu-Ser(P)-Ser(P)-Glu-Glu-NHMe.TFA were prepared by the use of Boc-Ser(PO3Ph2)-OH in the Boc mode of solution phase peptide synthesis followed by platinum-mediated hydrogenolytic de-protection of the Ser(PO3Ph2)-containing peptides. The protected peptides were assembled using the mixed anhydride coupling methods with 40% TFA/CH2Cl2 used for removal of the Boc group from intermediate Boc-protected peptides. PMID- 1446974 TI - Design and inhibitory properties of synthetic Bowman-Birk loops. AB - A cyclic tridecapeptide based on the sequence of an anti-tryptic loop of a Bowman Birk inhibitor was synthesized, and demonstrated to be active as an inhibitor of trypsin. Molecular modeling of this sequence suggested an improved sequence which demonstrated an order of magnitude improvement in the inhibitory constant. PMID- 1446975 TI - Reactive oxygen species as regulators of human neutrophil and fibroblast interstitial collagenases. AB - The effects of various reactive oxygen species on latent human neutrophil and fibroblast-type interstitial collagenases were studied. Latent human neutrophil collagenases (proMMP-8) was efficiently activated by hypochlorous acid and hydrogen peroxide and less efficiently by the serine proteinases trypsin and chymotrypsin. Human plasmin and plasma kallikrein did not activate latent human neutrophil collagenase. The activation of latent human neutrophil collagenase by hypochlorous acid and hydrogen peroxide corresponded to the activation obtained with the other known non-proteolytic activators phenylmercuric chloride and gold thioglucose. The activation by hydrogen peroxide was inhibited by mannitol and desferoxamine, suggesting a localized Fenton-type reaction to be responsible for the generation of hydroxyl radical and/or hydroxyl radical-like reactive oxygen pathway of neutrophil procollagenase does not involve plasmin and plasma kallikrein, which are efficient proteolytic activators of latent fibroblast-type procollagenase (proMMP-1). Fibroblast procollagenase was also slightly activated by hypochlorous acid and gold thioglucose. Thus neutrophil procollagenase seems to prefer non-proteolytic means of activation and reactive oxygen species can be regarded as potent activators in vivo. Synovial-fluid neutrophils from rheumatoid arthritis patients were found to release collagenase in 30% active form when compared to same patients' peripheral blood neutrophils, which released collagenase in completely latent form. This may indicate that the triggering of neutrophil at the site of inflammation in vivo involves initial oxidative activation of collagenase upon the degranulation process. PMID- 1446976 TI - Induction of Fc epsilon RII/CD23 on PHA-activated human peripheral blood T lymphocytes and association of fyn tyrosine kinase with Fc epsilon RII/CD23. AB - Despite the evidence for the expression of Fc epsilon RII/CD23, a glycoprotein that is a low-affinity Fc receptor for IgE, obtained on T cell lines and some pathological T cells, that of Fc epsilon RII/CD23 on normal human T cells is still unclear. We studied the emergence of T cells bearing Fc epsilon RII/CD23 in short-term culture of normal human peripheral blood mononuclear cells stimulated with 15 microliters/ml phytohemagglutinin (PHA). Using two-dimension flow cytometry, more than 10% of Fc epsilon RII/CD23(+) cells were shown to co-express CD3 antigen. Both CD4(+) and CD8(+) T cells expressed Fc epsilon RII/CD23. The expression of mRNA for Fc epsilon RII/CD23 on PHA and IL-4 stimulated PBMC was demonstrated by northern blotting and in-situ hybridization. The mechanism of signal transduction through Fc epsilon RII/CD23 was dissected by transfection of cDNA coding for Fc epsilon RII to the human natural killer-like cell line YT, activation of which was easily detected by the induction of interleukin-2 receptor/p55 (Tac). Cross-linking of Fc epsilon RII/CD23 with H107 anti-Fc epsilon RII monoclonal antibody enhanced IL-2R/p55 expression on YT cells transfected with Fc epsilon RII cDNA (YTSER). A possible involvement of protein tyrosine kinase in the Fc epsilon RII-mediated signal transduction was studied using YTSER. Fc epsilon RII was physically associated with an src-family tyrosine kinase p59fyn and not with p56lck, which was also found in YT cells. Recently it was reported that p59fyn was associated with T-cell antigen receptor. Our results collectively suggest the multiple function of p59fyn which may be implicated in the Fc epsilon RII-mediated activation signal in YT cells. PMID- 1446977 TI - Pefloxacin and immunity: cellular uptake, potentiation of macrophage phagocytosis and intracellular bioactivity for Klebsiella pneumoniae. AB - Antibiotic potentiation of host defence mechanisms may be of potential clinical importance in the outcome of infections. Therefore the effect of pefloxacin upon the interaction of in vitro of human macrophages with Klebsiella pneumoniae, by assays of antibiotic cellular uptake, bacterial phagocytosis and intracellular killing, was examined. The results indicated that pefloxacin was well concentrated by phagocytes at all the concentrations tested. The uptake proceeded rapidly and was not affected either by cell viability or physiological environmental temperature. Synergistic phagocytosis and intracellular killing of K. pneumoniae was observed in the presence of macrophages and subinhibitory concentrations (one-half MIC) of pefloxacin. Pretreatment of bacteria with pefloxacin led to an increase in both bacterial uptake and microbicidal activity of phagocytes. Exposure of the macrophages to pefloxacin did not affect any phagocyte functions. PMID- 1446978 TI - Changes of rabbit platelet function following simultaneous administration of Ticlopidine hydrochloride and Argipidine (MD-805). AB - Ticlopidine hydrochloride and Argipidine were administered simultaneously to rabbits and the changes in platelet function and coagulation-fibrinolysis were determined. Ticlopidine hydrochloride and Argipidine did not give rise to an additive or synergistic effect on the ADP-induced platelet aggregation. However, simultaneous administration of Argipidine and Ticlopidine hydrochloride significantly inhibited the collagen-induced platelet aggregation, as compared to the effect of single administration of Ticlopidine hydrochloride at 60 min after intravenous administration of Argipidine. Furthermore, at 90 min after the intravenous administration, the PAF-induced platelet aggregation in the simultaneous administration was significantly different from that in each individual administration. These results suggested that the effect of simultaneous administration on the platelet aggregation was dependent largely on the effect of Ticlopidine hydrochloride alone. PMID- 1446979 TI - Updating on in-vivo and in-vitro effects of heparin and other glycosaminoglycans (mesoglycan) on arterial endothelium: a morphometrical study. AB - Glycosaminoglycans, which include heparin, heparansulfate and dermatansulfate, are substances that exhibit many significant biological activities. In-vitro and in-vivo experiments for studying the effects of heparin and an association of heparan-like glycosaminoglycan and dermatansolfate (mesoglycan) on aortic arterial endothelium were performed. The studies were developed by means of computerized morphometric techniques. The in-vitro tests, performed on bovine aortic endothelial cells, have revealed an increase in survival rate, enhancement of cell density at confluence, and increase of nucleus/cytoplasm ratio, after "in vitro" administration of heparin or mesoglycan. The in-vivo tests have revealed a minor development of aortic intimal lipid deposition in mesoglycan-treated hypercholesterolaemic rabbits. Our morphometrical results confirmed by statistical tests strongly support the data collected in the literature over many years on the protective effects of mesoglycan and heparin on endothelium. PMID- 1446980 TI - Pollen gene expression: molecular evidence. PMID- 1446981 TI - Gametophytic self-incompatibility: biochemical, molecular genetic, and evolutionary aspects. PMID- 1446982 TI - Sporophytic self-incompatibility systems: Brassica S gene family. PMID- 1446983 TI - Sporophytic self-incompatibility systems: S gene products. PMID- 1446984 TI - Incidence of headache and severity of head injury. AB - The relationship between the incidence of post-traumatic headache and the severity of head injury has been a controversial issue. The milder the head injury, the more frequently severe headache is noted as a symptom. To investigate this relationship, 121 civilians were investigated using simplified classifications of the grade of headache, type of injury (mild or severe), cervical X-ray and head CT findings, and clinical history. All the subjects were claiming compensation for work-related injuries. In the mildly injured group, 46/64 patients complained of severe headache, while only 19/57 had severe headache in the severely injured group (p < 0.001). Abnormal findings on the cervical X-ray films including degenerative changes were more frequent in the severe headache group (p < 0.02). CT abnormalities correlated positively with the severity of head injury (p < 0.001), but showed an inverse relationship with the incidence of headache (p < 0.01). Mentally impaired patients also complained of headache less frequently (p < 0.01). On the basis of these results, possible organic mechanisms related to the pathogenesis of post-traumatic headache are discussed. PMID- 1446985 TI - Assessment of chronic refractory headache: the role of the MMPI-2. AB - We investigated the utility of the newly revised version of the Minnesota Multiphasic Personality Inventory, the MMPI-2, for assessing psychopathology in three diagnostic headache groups, Post Traumatic, Status Migrainosus, and Status Migrainosus with Analgesic Rebound. We also investigated whether distinct clusters of headache sufferers could be identified using the MMPI-2 clinical scales, and whether these clusters coincide with headache diagnosis. Eighty-one patients in treatment at the Houston Headache Clinic were diagnosed and administered the MMPI-2. Significant levels of psychopathology were found in all three diagnostic groups. Furthermore, Cluster analysis identified three clusters of patients with equal proportions of patients from the three diagnostic groups. Cluster 1 patients were abnormally high on many MMPI-2 clinical scales; Cluster 2 patients showed more moderate elevations, and Cluster 3 patients had essentially normal profiles. We concluded that the MMPI-2 offers additional information not available through medical diagnosis alone. Thus, it is crucial to include psychological assessment in any comprehensive evaluation of chronic headache patients. Further implications for treatment planning and effectiveness are discussed. PMID- 1446986 TI - Cerebrospinal fluid pressure and venous pressure in "dynamite headache" and cluster headache attacks. AB - Six patients with episodic cluster headache were investigated as to blood pressure, heart rate, cerebrospinal fluid pressure (Pcsf) and frontal vein pressure (Pvf) during five nitroglycerin (NG) provoked attacks and one spontaneous attack. In a seventh studied patient the NG failed to provoke an attack. The earlier reported decrease of systolic blood pressure and increase of diastolic blood pressure and heart rate after NG administration were also found in these patients. The "dynamite headache" was related to the start and duration of an increase of the cerebrospinal fluid pressure. There was no relationship between the start or the maximum pain of the cluster headache attack and changes in Pcsf or Pvf. On breathing oxygen during a cluster headache attack, there was a decrease of Pcsf but in some patients a temporary increase of Pvf was observed, which possibly indicates that oxygen simultaneously attains constriction of arteries and veins. PMID- 1446987 TI - Chronic daily headache: long-term prognosis following inpatient treatment with repetitive IV DHE. AB - We retrospectively studied the long-term (2-year) outcome of 50 consecutive patients admitted to our inpatient headache program because of chronic daily headache (CDH) associated with the overuse of analgesics, ergotamine, or both. They had been detoxified, given repetitive intravenous dihydroergotamine (IV DHE) and prophylactic medications as part of the program, and had become headache-free on this regimen. At the time of admission, 37 of the 50 patients had transformed migraine (TM), 12 had new daily persistent headache (NDPH), and 1 had chronic tension-type headache; 29 of the patients with TM, 7 of those with NDPH, and the single patient with chronic tension-type headache had coexistent migraine. Substances abused, alone or in combination, included: caffeine in 39 patients (av. 441 mg/d), acetaminophen in 32 (av. 2187 mg/d), aspirin in 24 (av. 1807 mg/d), ibuprofen in 9 (av. 1156 mg/d), narcotics in 7 (av. 10.1 mg morphine equivalents/d) and ergotamine in 11 (av. 2.3 mg/d). Twenty patients were using preventive medication at the time of admission. Follow-up evaluations were performed at 3, 6, 12, and 24 months after discharge. Forty-three patients were analyzed at 3 months. Of these, 44% had an excellent or good result and 28% a fair result; 3 were overusing analgesics. At 24 months, 39 patients were analyzed: 59% had a good or excellent result and 28% a fair result; 5 were overusing analgesics, 4 of whom were doing poorly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446988 TI - Cerebral blood flow in migraine with aura: a transcranial Doppler sonography study. AB - Transcranial Doppler sonography examination was performed on 44 patients with migraine with aura and 88 controls. All patients were investigated in headache free periods and 10 of them also during a migraine attack. During the headache free period a not significant increase of mean flow velocity in patients compared to controls was obtained. The pulsatility index (PI) mean values were also higher in patients than in controls and the differences were significant in the MCA (p < 0.05). No difference between right and left side was observed. During the attack the mean flow velocity (MFV) decreased in all arteries but the decrease was significant only in MCA and ACA (p < 0.05). The mean PI increased in all arteries but not significantly. These variations were observed both on the headache and contralateral side. Nevertheless, the MFV decrease in all arteries was observed in four patients only. In four patients the MFV decrease was found in the anterior arteries and the MFV increase in the posterior arteries, while in two patients the MFV increase was observed both in the anterior and posterior arteries. The correlation between the variations of MFV values during the attacks and the time interval from the onset of attacks showed that the PCA and BA flow velocities were increased in patients examined between 0.5 and 3 hours, while an increase in MCA and ACA flow velocities were observed only in patients examined after 1.5 hours. PMID- 1446989 TI - Self-administration of parenteral ketorolac tromethamine for head pain. AB - Sixty-one separate self-injections of ketorolac tromethamine (Toradol) by 16 patients diagnosed with episodic migraine with or without aura were evaluated over a 90-day period for safety, efficacy of pain reduction, and the ability of this therapy program to prevent the necessitation of emergency room acute care. Prior to initiation of treatment, patients were formally instructed on intramuscular injection techniques by a member of our nursing staff. Patients were instructed to call upon the onset of a severe headache interfering with daily functioning and, then, were permitted to proceed with the injection. Headache intensity ratings were collected prior to injection and intermittently for the following twenty-four hours. The results demonstrate safety and efficacy of this form of therapy. A significant percent of ketorolac usages (64%) resulted in a good response and significant reduction in head pain. Twenty-three percent of ketorolac usages resulted in a mild response and only 13% of usages provided no relief. Furthermore, 13% of all usages failed to prevent the necessitation for emergency room treatment. The results are discussed in terms of the impact of self-injection on pain relief and substantial cost-reduction by decreasing emergency room utilization. PMID- 1446990 TI - Outpatient repetitive intravenous dihydroergotamine. AB - The efficacy of the repetitive intravenous dihydroergotamine (DHE) inpatient protocol for refractory headache is well established. We conducted a retrospective and prospective study of long-term headache patients at our clinic to evaluate this regimen in an outpatient setting. Treatment consisted of oral metoclopramide and four doses of DHE, with the total dose equaling 4 mg., administered over two days. Patients were followed for up to 10 weeks while they continued to receive prophylactic medication. Responsiveness was rated in terms of decreased frequency or severity of headache: excellent (75% to 100%), moderate (50-75%), mild (25-50%), and none (0-25%). In the retrospective study, 69% (43/62) of patients with chronic daily muscle-contraction-type headache and severe migraine had an excellent response at two days. An excellent or moderate response was sustained over three weeks in 65% (32/49) of the study group (13 patients were dropped from the study for failing to comply with record keeping requirements). At the 6- and 10-week follow-up evaluations, the majority of patients (76% and 70%, respectively) reported mild or no relief. Among patients with refractory daily headache or frequent severe migraine studied prospectively, 80% (28/35) reported an excellent response at two days. After six weeks, 66% (23/35) showed excellent or moderate relief. For both groups combined, 73% (71/97) of patients showed an excellent response to DHE at two days, with 43% (33/77) sustaining excellent or moderate relief at six weeks. Side effects, including nausea, leg cramps, facial flushing, increased blood pressure, diarrhea, burning at the injection site, and tightness in the throat and/or chest, were generally mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1446992 TI - Flunarizine in migraine: a double-blind placebo-controlled study (in a Saudi population). AB - We evaluated the effect of flunarizine (Fz) (10 mg/d) on migraine in a double blind placebo-controlled design. The attacks' frequency, duration, severity and associated symptoms were compared before and after treatment. Forty-two patients completed a three-month trial period; 21 patients received Fz and 21 placebo. Statistical analysis showed no significant difference between Fz and placebo (p > 0.05). In this study Fz was not more efficient than placebo in migraine. PMID- 1446991 TI - Unilateral headache with features of hemicrania continua and cervicogenic headache--a case report. AB - A case is presented which has features of Cervicogenic Headache and of Hemicrania Continua. A sudden maneuver of the neck and later a greater occipital nerve block, both resulted in relief of the pain. A cervical cause is suggested. PMID- 1446993 TI - "Raynaud's disease" in migraineurs: one entity or two? AB - Two cases are reported of patients who were diagnosed as having both migraine and Raynaud's disease. Because they were able to achieve effective control of both headaches and extremity temperature after undergoing a comprehensive approach- utilizing medication, biofeedback, and psychotherapy--it is suggested that both conditions are manifestations of the same disorder. It is recommended that a first step in approaching concurrent diagnoses of this type involve combined treatment as is often used in response to the singular diagnosis of migraine. PMID- 1446994 TI - Ear pain due to cervical spine arthritis: treatment with cervical facet injection. PMID- 1446995 TI - Ergotamine-metoclopramide for migraine: is it enough? PMID- 1446996 TI - The relationship of resting and exercise blood pressure in subjects with essential hypertension before and after drug treatment with propranolol. AB - OBJECTIVE: To investigate the relationship between clinic resting blood pressure (BP) and exercise BP in subjects with established essential hypertension during placebo and propranolol-treated phases. DESIGN: Prospective, placebo-controlled, cross-over trial. SETTING: University-affiliated medical center. PATIENTS: A convenience sample of 38 patients with essential hypertension, 34 men and four women, who ranged in age from 22 to 62 years (mean = 44 years, SD = 10.7). Subjects were diagnosed with mild to moderate diastolic or mixed systolic/diastolic essential hypertension at least 1 year before study entry. They had no clinical evidence of secondary hypertension, diabetes, heart, liver, pulmonary, or renal disease. OUTCOME MEASURES: Resting and exercise BP. INTERVENTION: Antihypertensive medication was tapered off and subjects were free of all prescription drug treatment for 2 weeks. They received placebo for an additional 2 weeks. Subjects then received treatment with propranolol at a dose necessary to control resting blood pressure for 4 to 6 weeks. At the end of both the untreated and treated phases, subjects were given a graded maximal exercise test on a bicycle ergometer. RESULTS: Propranolol effectively reduced mean resting and maximal exercise BP. The nonsignificant correlation between clinic resting and maximal exercise systolic BP was low in both phases. The correlation between clinic resting and maximal exercise diastolic BP was only moderate, but statistically significant (untreated, r = 0.43; p < 0.01; treated, r = 0.53; p < 0.001). For systolic BP or diastolic BP, there were no significant relationships between percent drop in BP because of propranolol at rest or maximal exercise. Clinic resting BP was not a valid predictor of maximal exercise BP. Degree of control of clinic resting BP was not a valid predictor of control observed at maximal exercise. CONCLUSIONS: Resting BP should not be used as a predictor of BP during maximal exercise in the untreated condition or with treatment with propranolol. PMID- 1446997 TI - Effects of ventricular ectopy on sinus R-R intervals in patients with advanced heart failure. AB - OBJECTIVE: To determine the effect of ventricular ectopy on subsequent sinus R-R intervals. DESIGN: Comparative, repeated-measures design. SETTING: University medical center. SUBJECTS: Ten consecutive sinus R-R intervals and their standard deviations before and after ventricular ectopy from 24-hour ambulatory electrocardiogram recordings were obtained from 25 patients with heart failure (left ventricular ejection fraction 0.18 +/- 0.08; New York Heart Association Functional Class III-IV) and three healthy subjects. RESULTS: The effects of 7564 single ventricular ectopic beats, 272 ventricular couplets, and 49 episodes of ventricular tachycardia in the patients with heart failure and 1369 single ventricular ectopic beats in the three healthy subjects were evaluated. Repeated measures ANOVA indicated no significant differences in sinus R-R intervals immediately before or after ventricular ectopy. Standard deviation of sinus R-R intervals before and after ventricular ectopy did not differ significantly. CONCLUSIONS: Ventricular ectopy does not significantly alter subsequent sinus R-R intervals and is unlikely to affect measurement of heart rate variability, particularly by techniques that use standard deviation methods. PMID- 1446998 TI - Attention versus avoidance: attributional search and denial after myocardial infarction. AB - OBJECTIVE: In this study the focus was on two strategies: denial (an avoidant strategy) and causal thinking (an attention strategy) and their relationships to affect after myocardial infarction. DESIGN: Descriptive, correlational. SETTING: Large rural medical center. SAMPLE: The sample comprised 152 recently hospitalized patients with first-time myocardial infarction. MEASURES: A denial scale, a question about causal thinking, and an affect adjective checklist measuring anxiety, hostility, and depression. RESULTS: Denial had a weak but significant negative correlation with anxiety (r = -0.18, p < 0.05). However, denial was not significantly related to either depression or hostility. Regression analysis indicated that both denial (F = 4.84, p = 0.02) and the interaction of denial with causal search (f = 4.77, p = 0.009) were predictors of affect. The interaction indicated that those with high denial who had not searched for a cause were least anxious. A large number of subjects used both attention and avoidant strategies. CONCLUSIONS: The main effect for denial suggests that avoidance is a more effective strategy for reducing anxiety after myocardial infarction than causal search, an attention strategy. However, the fact that many subjects used both strategies suggests that they are not mutually exclusive in the process of adaptation after a heart attack. PMID- 1446999 TI - Does overprotection cause cardiac invalidism after acute myocardial infarction? AB - OBJECTIVE: To determine if overprotection on the part of the patient's family and friends contributes to the development of cardiac invalidism after acute myocardial infarction. DESIGN: Longitudinal survey. SETTING: Nine hospitals in the southwestern United States. SUBJECTS: One hundred eleven patients who had experienced a first acute myocardial infarction. Subjects were predominantly male, older-aged, married, caucasian, and in functional class I. Eighty-one patients characterized themselves as being overprotected (i.e., receiving more social support from family and friends than desired), and 28 reported receiving inadequate support. Only two patients reported receiving as much support as they desired. OUTCOME MEASURES: Self-esteem, emotional distress, health perceptions, interpersonal dependency, return to work. RESULTS: Overprotected patients experienced less anxiety, depression, anger, confusion, more vigor, and higher self-esteem than inadequately supported patients 1 month after myocardial infarction (p < 0.05). Inadequately supported patients were more dependent 4 months after the event. CONCLUSIONS: Overprotection on the part of family and friends may facilitate psychosocial adjustment in the early months after an acute myocardial infarction rather than lead to cardiac invalidism. PMID- 1447000 TI - Coronary care patients' and nurses' perceptions of important nurse caring behaviors. AB - OBJECTIVE: To examine the relationship of patient-perceived and nurse-perceived caring behaviors. DESIGN: Descriptive. SETTING: Three not-for-profit hospitals in a large metropolitan western city. SUBJECTS: Thirty coronary care patients and 30 coronary care nurses. METHOD: Larson's nurse caring behaviors (CARE-Q) were rank ordered by the Q-sort method. RESULTS: The patient's study group perceived behaviors that involved technology as most important, which differed from nurses, who perceived listening as the most important caring behavior. CONCLUSIONS: This study supports the findings of other researchers that patients' and nurses' perceptions of important nurse caring behaviors are divergent. PMID- 1447001 TI - Perceived stress and coping strategies among families of cardiac transplant candidates during the organ waiting period. AB - OBJECTIVE: To explore and describe perceived stress and coping strategies among families of candidates for cardiac transplant during the organ waiting period. DESIGN: This descriptive, multiinstitutional study was guided by the T-Double ABCX Model of Family Adjustment and Adaptation (McCubbin & Thompson, 1987). SETTING: Five tertiary care centers with transplant programs in three Southeastern cities. SUBJECTS: Thirty-eight family members of patients on the active list for cardiac transplantation, including 35 women and three men with a mean age of 44 years (SD = 13.17). Subjects had a family member on the waiting list for a mean of 6.5 months. INSTRUMENTS: Family members completed the following three instruments: (1) Family Inventory of Life Events and Changes (FILE), (2) Family Crisis Oriented Personal Scale (FCOPES), and (3) Family Perception of the Transplant Experience Scale (FPTES). RESULTS: Stress: 53% and 47% of respondents indicated that they were experiencing moderate and low degrees of stress, respectively. Coping: Family members used more coping mechanisms than normative subjects in the literature. Coping strategies used in order of decreasing frequency: (1) knowing our family has the strength to solve our problems, (2) facing problems head-on, and (3) seeking support from friends. Appraisal: Mean score of 32.13 reflects subjects' positive perception of the pretransplant experience. The three statements with which the subjects most strongly agreed: (1) heart illness has changed roles of family members, (2) family member will survive the transplant operation; and (3) this is an experience that could bring out the family's strengths. CONCLUSIONS: An increase in the number of coping strategies used with low to moderate stress levels suggests the effectiveness of coping strategies in mediating stress. The preference for active rather than passive coping strategies may be reflective of the selection criteria for transplant candidates or nursing interventions during this period to minimize stress and promote family coping. PMID- 1447002 TI - The Glasgow Coma Scale: time for change. AB - OBJECTIVE: To summarize and evaluate evidence on the psychometric properties of the Glasgow Coma Scale (GCS). RESULTS: This instrument attempts to capture the phenomenon of consciousness with three gross indicators of nervous system function. Although the GCS does capture consciousness to a limited extent and has pragmatic utility for practitioners, it suffers serious limitations for clinical monitoring and prediction and is being eclipsed by a variety of other instruments. CONCLUSION: In spite of its acknowledged shortcomings and the emergence of parallel instruments with greater reliability and validity, the GCS continues to enjoy a privileged, but unwarranted, position in clinical and investigational contexts. PMID- 1447003 TI - Analysis of motor vehicle crash data in an urban trauma center: implications for nursing practice and research. AB - OBJECTIVE: To examine the incidence of risk behaviors (safety restraint use and alcohol use) and demographic characteristics of motor vehicle crash victims. DESIGN: Retrospective, descriptive, correlational. SETTING: One major, urban, Level 1 trauma center. SUBJECTS: The medical records of 864 motor vehicle crash victims (drivers, passengers, pedestrians, bicycle riders, and motorcycle riders) admitted to the trauma center between July 1, 1989, and June 30, 1990, were reviewed. RESULTS: Eighty-two percent of motor vehicle occupants (403 drivers and passengers) were not wearing safety restraints at the time of the crash. Thirty six percent of drivers (92) and 42% (47) of pedestrians were intoxicated on admission to the trauma center. Failure to use safety restraints was associated with alcohol use in this population. Subjects who engaged in risk behaviors were predominantly adolescent and young adult males. CONCLUSIONS: These data suggest the need for further research into correlates of risk behaviors and interventions to prevent future injury related to these behaviors. PMID- 1447004 TI - Perceived uncertainty, physical symptoms, and negative mood in hospitalized patients with chronic obstructive pulmonary disease. AB - OBJECTIVE: To determine whether perceived uncertainty and physical symptoms were related to negative mood in hospitalized patients with chronic bronchitis and/or emphysema. DESIGN: Descriptive correlational. SETTING: Five large teaching hospitals in a city in central Canada. SUBJECTS: The sample consisted of 15 men and 11 women ranging in age from 53 to 86 years. INSTRUMENTS: Mishel Uncertainty in Illness Scale; Somatic Scale of the Bronchitis Emphysema Symptom Checklist; and Tension, Depression and Anger Subscales of the Profile of Mood States. RESULTS: Only the variable of physical symptoms contributed to the negative mood of the subjects with chronic obstructive pulmonary disease, explaining 21% of the variance (p < 0.02). Of the four symptom categories measured (fatigue, dyspnea, congestion, and peripheral-sensory disturbance), only fatigue was a significant predictor (p < 0.006) of negative mood, accounting for 28% of the variance. CONCLUSION: Negative mood is evidence of impaired coping. The finding that fatigue contributed to negative mood provides support for the theoretic prediction that low energy interferes with an individual's ability to cope with a stressful situation. PMID- 1447006 TI - Empty Wenckebach pauses. PMID- 1447005 TI - Ventilator-assisted patient vocalization with positive end-expiratory pressure and tracheostomy cuff leak: a brief report. AB - OBJECTIVE: To enable vocalization in a tracheostomized ventilator-assisted patient without compromising pulmonary status. DESIGN: Case report. SETTING: University-affiliated nonprofit hospital. PATIENT: A 62-year-old man with a medical history of metastatic lung cancer and chronic obstructive pulmonary disease received mechanical ventilation for 24 days. On the twenty-first day of ventilation the patient requested in writing the desire to vocalize with his family. INTERVENTION: Flow-generated positive end-expiratory pressure of +3 cm of water (PEEP of 3 cm H2O) was applied to the patient's airway and the tracheostomy cuff was slowly deflated to create a cuff leak. The patient was instructed to phonate the letter /a/ until the sound became audible. Lack of voice intensity necessitated PEEP titration of 1 cm H2O increments until 8 cm H2O of PEEP intensified the voice. CONCLUSION: During each session, the patient was able to vocalize clearly, without complications, as measured by the physiologic parameters: heart rate, respiratory rate, blood pressure, and oxygen saturation determined by oximetry. PMID- 1447007 TI - Special requirements for residency training in radiation oncology. Radiation Oncology Subcommittee of the Residency Review Committee for Radiotherapy. PMID- 1447008 TI - Education in radiation oncology in Europe. AB - The outcome of an inventory among 22 European countries with respect to the radiotherapy facilities and the training of new radiation oncologists in each country is described. The radiotherapeutic profession, which mostly prescribes also cytostatics or hormones, has become well-regulated in the last 20 years. Most radiation oncologists are also involved in the diagnostic work-up and follow up of the cancer patient. The numbers of radiotherapists and other staff, treatment capacities, and patients are given. The training for radiation oncologists is mostly taken at the university centers, but the curricula are rather diverse. PMID- 1447009 TI - Training in radiation oncology in the United Kingdom. PMID- 1447010 TI - Principles of radiation oncology training and manpower requirements in Canada. PMID- 1447011 TI - Training in radiotherapy in The Netherlands. AB - The training in radiotherapy in The Netherlands is an example of a master apprentice system. In this overview we will discuss the organization and describe the official bodies involved in the Dutch training programs. Also the contents and the system of accreditation are presented. PMID- 1447012 TI - Swedish requirements for residency training in oncology. PMID- 1447013 TI - Training curriculum in oncology in France. Conseil des Enseignants de Radiotherapie Oncologie (CERO). PMID- 1447014 TI - Residency training in radiation oncology; radiation biology and cancer biology. PMID- 1447015 TI - Radiation physics instruction for residents. PMID- 1447017 TI - Accreditation of radiation oncology in the United States. PMID- 1447016 TI - Residency training for medical physicists. PMID- 1447018 TI - Specific requirements for the accreditation of residency programs in Canada. PMID- 1447019 TI - Accreditation process in the United Kingdom. PMID- 1447020 TI - Higher training and continuing medical education in radiation oncology in the United Kingdom. PMID- 1447021 TI - International comparison of postgraduate medical education in radiation oncology. AB - Despite variances in length, scope and content of postgraduate medical education in radiation oncology, there is a thread of commonality that runs through all programs. Aside from the emphasis on internal medicine in Canada and the emphasis on technical radiotherapy in the United States, it is surprising how little different content and duration of training are between the two countries. Similarly, there is movement to standardize training in radiation oncology in Europe that parallels the development of the European Community and the desire of physicians to cross borders. PMID- 1447022 TI - Policy statement on the accreditation of subspecialty programs. PMID- 1447023 TI - Brachytherapy as a model for subspecialization within radiation oncology. PMID- 1447024 TI - Pediatric radiation oncology--subspecialty training? PMID- 1447025 TI - Subspecialization in radiation oncology: impact of stereotactic radiosurgery. PMID- 1447026 TI - Is a fourth year necessary? The need for subspecialization: total body irradiation. AB - Although the number of radiation oncologists performing TBI procedures has increased in the last decade and there exists a significant body of unique medical knowledge pertinent to its use, there is little cohesiveness as a discipline within radiation oncology. There are no specific societies, journals, and no hospital divisions devoted to this area. Therefore, I content that subspecialty accreditation is not justified at this time. However, there are many fascinating scientific questions at the cellular, tissue, and clinical level which remain to be answered with regard to TBI, making it an exciting area for both laboratory and clinical research. Specialized training should be offered by institutions with expertise as a possible research year for residents and/or fellows who have a particular interest in pursuing an academic career along these lines. PMID- 1447027 TI - The need for subspecialization: intraoperative radiation therapy. AB - Intraoperative radiation therapy represents a technically complex branch of radiation oncology which is undergoing intensive study. Further results of randomized Phase III trials must be available before IORT is established as an effective modality. The majority of residency training programs do not have IORT available and the use of IORT is not required for initial certification in radiation oncology. Residents could be educated in the principal concepts and the technical details of IORT and should be knowledgeable in the results of clinical trials in IORT. At the present time the leading investigators in IORT should consider offering a special research year or fellowship training in an appropriate residency training facility. If Phase III trials of IORT prove positive in a number of sites it is likely that this modality will become mainstream and then training in IORT should be required of all radiation oncology residents. Certainly there is insufficient evidence for subspecialty certification in IORT at the present time. However, one should not construe from this statement that special training in IORT is not required for its appropriate use. On the contrary, given the potential for morbidity and yet to be proven efficacy, special training in IORT should be undertaken in centers of excellence in IORT and patients treated with IORT should be entered in clinical trials whenever possible. PMID- 1447028 TI - Training in systemic radiation therapy. PMID- 1447029 TI - Is a fourth year necessary in radiation oncology training? Different models and funding mechanisms. PMID- 1447030 TI - The case for a three year residency program in radiation oncology. PMID- 1447031 TI - Results of the in-training examination of the American College of Radiology for Residents in RAdiation Oncology. PMID- 1447032 TI - The role of residents in residency training. PMID- 1447033 TI - Review of the manpower issue in radiation oncology. PMID- 1447034 TI - Seminoma of the testis: long-term beneficial and deleterious results of radiation. AB - PURPOSE: The followup of 387 patients in a USA national survey of seminoma treated with radiation in 1973 and 1974 has been extended beyond 15 years to assess the long-term benefits and problems resulting from treatment. RESULTS: Survival at 15 years is 83% for Stage I, 68% for Stage II; freedom from recurrence at 15 years is 93% for Stage I, 96% for Stage II; NED survival at 15 years is 80% for Stage I, 68% for Stage II; cause specific freedom from cancer death is 98% for Stage I and 97% for Stage II at 15 years. Second malignancy rates were 8% at 15 years, and observed in 14 patients versus 4.2 expected (p < .001). Deaths due to these second cancers were also increased with seven observed versus two expected (p < .01). Non-cancer intercurrent disease death occurred in 23 patients versus 7.5 expected (p < .01). The most frequent cause was cardiac death which appeared in 10 patients versus 4.4 expected (p < .05) and 8 of the 10 patients received mediastinal radiation. Two additional patients died of pulmonary fibrosis after mediastinal radiation. Mediastinal radiation correlated with all intercurrent disease and cardio-pulmonary deaths (p < .05), but not with second malignancies. With the exception of one, all patients experiencing cardiac death after mediastinal irradiation were 40 years or older at the time of treatment, with a range of 32-58 years and a mean interval to death of 9.8 years. CONCLUSIONS: Recommendations for the future management of seminoma include: reducing the irradiated volume in the treatment of Stage I patients, completely eliminating mediastinal radiation in the treatment of patients with Stage IIA seminoma and treating patients with Stage IIB seminoma with chemotherapy. Radiation dose should not exceed 30 Gy for Stage I or 35 Gy for Stage IIA. PMID- 1447035 TI - Impact of adjuvant therapy on locally advanced adenocarcinoma of the stomach. AB - From 1975 to 1988, 120 consecutive patients with locally advanced (T3/T4 or N1/N2) adenocarcinoma of the stomach underwent attempted curative resection. Seventy patients were treated with surgery alone while 50 patients also received adjuvant therapy consisting of either chemotherapy (5-FU/FAM) alone, radiation therapy alone, or chemotherapy+radiation therapy. Adjuvant therapy was tolerated relatively well with only one patient experiencing a grade 3 (RTOG/EORTC) toxicity, and none experiencing grade 4/5 toxicity. In patients with T3/T4 tumors, the median survival was 10 months for surgery alone as compared to 18 months for the adjuvant treatment group, and a 5-year survival of 10% versus 24% in the adjuvant therapy group (p = .01). In patients with lymph node positive disease, the median survival was 10 months in patients treated with surgery as compared to 15 months for those treated with adjuvant therapy, and a 5-year survival of 8% for surgery alone versus 16% for the adjuvant therapy group (p = .04). Patients having both T3/T4 tumor and positive lymph nodes had a median survival of 9 months with surgery versus 13 months for the adjuvant therapy group, and a 5-year survival of 4% versus 22% (p = .03) for the adjuvant group. Seventy-four patients were evaluable for pattern of relapse. Thirty developed locoregional recurrence; 17 of 38 (45%) in the surgery alone group and 13 of 36 (36%) in the adjuvant therapy group. The improvement in local control in the adjuvant group was totally accounted for by the group receiving both chemotherapy and radiation therapy, in which the recurrence rate was 19%. Statistically significant improvement in the 2-year local control rate was limited to patients with negative surgical margins who received radiation, 93%, versus those who did not, 55% (p = 0.03). The modest improvement in survival seen in patients receiving adjuvant therapy appears to be related to improved local control. No improvement in the rate of distant failure was seen. Chemotherapeutic regimens used seem to be critical in enhancing the effects of radiation in improving local control and survival. Results may be further improved by the extended use of intraoperative radiation. PMID- 1447036 TI - Enhanced induction of tissue-type plasminogen activator in normal human cells compared to cancer-prone cells following ionizing radiation. AB - Normal human fibroblast (i.e., GM2936B, GM2907A, and IMR-90) and cancer-prone human fibroblast (i.e., Fanconi's anemia, Bloom's syndrome, and Ataxia telangiectasia) cells demonstrated the induction of intracellular and extracellular levels of tissue-type plasminogen activator (t-PA) at 6 and 12 hr, respectively, following ionizing radiation. Induced t-PA enzymatic activities following ionizing radiation were blocked by actinomycin D treatments. t-PA enzymatic activities were induced over 14-fold in Ataxia telangiectasia cells, over 9-fold in Bloom's syndrome cells, and over 6-fold in Fanconi's anemia cells, as compared to normal human fibroblasts. Similarly, the induction of t-PA mRNA levels in cancer-prone cells were between 5- to 10-fold higher than those observed in normal cells following equitoxic doses of ionizing radiation. Temporal induction of t-PA mRNA levels for normal and cancer-prone human cells were consistent with quantifiable enzymatic activities. The elevated induction of an intracellular protease (i.e., t-PA) in cancer-prone human cells is reminiscent of an "SOS"-like response observed in yeast and bacteria. PMID- 1447037 TI - Pharmacokinetics of intratumoral RK-28, a new hypoxic radiosensitizer. AB - RK-28 is one of the new hypoxic cell radiosensitizers being developed in Japan and has been tested clinically. To reduce its toxicity and increase its sensitizing activity, intratumoral injection of RK-28 was performed during intraoperative radiation therapy for pancreatic cancer. This report presents the results of pharmacokinetic studies performed in 10 of the 17 patients who were administrated intravenous or intratumoral RK-28 during intraoperative radiation therapy. No adverse effects were noted following intravenous or intratumoral injection of the drug. Pharmacokinetic studies demonstrated several metabolites of RK-28 in both serum and tumor tissues. After intratumoral injection, the tumor drug concentration ranged from 123 micrograms/g to 9,292 micrograms/g just after intraoperative radiation therapy (30-50 min after injection of the compound), while the serum concentration ranged from 4.1 to 9.8 micrograms/ml. The tumor drug concentration was 23.3 micrograms/g at 45 min after intravenous injection of RK-28. Thus, intratumoral injection of RK-28 was superior to intravenous administration in this pharmacokinetic study. The combination of intraoperative radiation therapy and intratumoral injection of RK-28 appears to be a feasible treatment method. PMID- 1447038 TI - Elimination of dose-rate effects by mild hyperthermia. AB - PURPOSE: Preferential amplification of low dose-rate irradiation toxicity in tumor cells is one way of improving presently applied brachytherapy. Low temperature hyperthermia applied to a tumor volume during irradiation is one candidate for reaching this goal. The ranges of relevant temperatures and dose rate have been determined in a tissue culture system. In addition, the role of inhibition of sublethal damage repair in inhibition of dose-rate sparing has been investigated. METHODS AND MATERIALS: Dose-rate modification by long duration, mild hyperthermia was investigated in rat 9L gliosarcoma cells at dose-rates between 0.0833 and 132 Gy/hr. Enhancement of toxicity was measured using the colony formation technique. RESULTS: A biphasic dose-rate effect curve was observed when cells were irradiated at 37 degrees C. The dose required to kill 99% of cells irradiated at 37 degrees C increased sharply between 20 and 5 Gy/hr and also below 1 Gy/hr. When cells were irradiated at 41 degrees C, dose-rate sparing disappeared from 132 to 0.0833 Gy/hr. Elimination of dose-rate sparing appeared to be caused by both inhibition of sublethal damage repair and blockage of cell proliferation. The temperature threshold for sensitizing low dose-rate irradiation was determined at temperatures between 24 degrees C and 41 degrees C during 0.5 Gy/hr irradiation. Temperature dependent sensitization occurred above 39 degrees C. The mechanisms by which low temperature hyperthermia sensitizes low dose-rate irradiation was investigated using split dose experiments. Survival curve shoulder recovery was inhibited when cells were incubated at 41 degrees C between acute irradiations. This effect appeared to be caused by both inhibition of recovery from sublethal damage from the first radiation and preheating sensitization of the second irradiation. In single acute dose experiments, sensitization from preheating at 41 degrees C increased gradually over a 6 hr period. CONCLUSIONS: The mechanism by which 41 degrees C hyperthermia sensitizes low dose-rate irradiation is inhibition of radiation repair at medium dose rates and inhibition of repair and proliferation at very low dose rates. If low temperature hyperthermia is able to sensitize human tumor cells to brachytherapy similar to what has been described with 9L gliosarcoma cells, the addition of this modality could potentially greatly improve presently applied therapy. PMID- 1447039 TI - Consideration of radiation quality in treatment planning with p(66)/Be(40) neutrons. AB - A thorough microdosimetric investigation of a p(66)/Be(40) neutron therapy beam has been performed employing a commercial tissue equivalent proportional counter. Using y* as a monoparameter of radiation quality, variations in the potency of the beam have been discerned with spatial position and for different field sizes in a water phantom. The identified variations with depth are attributed solely to changes in the character of the neutron component of the beam. When increasing the field size, neutron effects are tempered by an increasing photon component. To accommodate these quality changes in the prescription of absorbed dose, the concept of effective dose is invoked and elementary expressions are proposed to assess this quantity. A simple four-field treatment plan is calculated to show that if unaccounted for, the quality changes with depth alone would result in a 4% discrepancy between the prescribed and effective dose delivered to the tumor volume. The implications for optimum dose delivery in clinical practice are discussed in terms of these findings. PMID- 1447041 TI - Subspecialization in radiation oncology. PMID- 1447040 TI - Recent patterns of growth in radiation therapy facilities in the United States: a patterns of care study report. AB - The Patterns of Care Study conducted its seventh survey of radiation oncology facilities with megavoltage equipment. The aims were to identify the basic structural characteristics of the radiation oncology specialty, to allow comparison with previous surveys, to identify trends in the patterns of equipment and personnel usage, and to measure the capabilities of facilities to deliver modern radiotherapy. All radiation oncology facilities in the United States and Puerto Rico were surveyed. Multiple mailings and calls yielded identification of and responses from virtually all facilities doing megavoltage radiotherapy. The survey collected information on equipment, patient load, personnel, and types of procedures performed. The complete census was reviewed, summarized, and compared to previous surveys. Results for 1990 showed 1321 facilities, (938 hospital based, 350 freestanding, 33 federal), 492120 new patients, and 2397 treatment machines (1893 linear accelerators or betatrons and 504 cobalt machines). The number of facilities and total machines increased rapidly with most of the increase in facilities occurring in the freestanding category. The number of cobalt units declined, while the number of linear accelerators increased. The results also showed that 6% of facilities did not have the capability of simulating patients and 7% of facilities did not have treatment planning capability. Of all facilities 9% reported doing intraoperative radiation therapy and 18% doing hyperthermia. For recent years in the specialty of radiation oncology the number of facilities and treatment machines increased at a more rapid rate than the number of new patients. PMID- 1447042 TI - Japanese system for training radiation oncologists. PMID- 1447043 TI - Response to the residency match in radiation oncology. PMID- 1447044 TI - The "bottom line"--response to Dr. Hanks. PMID- 1447045 TI - [Nursing record for maternal health care. Evaluation of a study]. PMID- 1447046 TI - [Report from a seminar on active birth]. PMID- 1447047 TI - ["Women's psychological development". Report from a day course in the Institute for Women's Psychology]. PMID- 1447048 TI - [Abortion problem in a comparative study: Sweden--Italy]. PMID- 1447050 TI - [Psychological acute care for newborn infants]. PMID- 1447049 TI - [Symphysiotomy--a forgotten but life-saving procedure]. PMID- 1447051 TI - [Psychological support during childbirth]. PMID- 1447052 TI - [Bath after rupture of membranes]. PMID- 1447053 TI - [I love you my little baby...]. PMID- 1447054 TI - A comparison of the sensitivity of wound-infecting species of bacteria to the antibacterial activity of manuka honey and other honey. AB - Both honey and sugar are used with good effect as dressings for wounds and ulcers. The good control of infection is attributed to the high osmolarity, but honey can have additional antibacterial activity because of its content of hydrogen peroxide and unidentified substances from certain floral sources. Manuka honey is known to have a high level of the latter. Seven major wound-infecting species of bacteria were studied to compare their sensitivity to the non-peroxide antibacterial activity of manuka honey and to a honey in which the antibacterial activity was primarily due to hydrogen peroxide. Honeys with activity in the middle of the normal range were used. A comparison of the median response of the various species of bacteria showed no significant difference between the two types of activity overall, but marked differences between the two types of activity in the rank order of sensitivity of the seven bacterial species. The non peroxide antibacterial activity of manuka honey at a honey concentration of 1.8% (v/v) completely inhibited the growth of Staphylococcus aureus during incubation for 8 h. The growth of all seven species was completely inhibited by both types of honey at concentrations below 11% (v/v). PMID- 1447055 TI - Evaluation of antimicrobial interactions between chlorhexidine, quaternary ammonium compounds, preservatives and excipients. AB - The antimicrobial interactions of 49 combinations of chlorhexidine, quaternary ammonium compounds, preservatives and excipients were evaluated by the method of Berenbaum and the checkerboard titration method, with Staphylococcus aureus CIP 53154 and Escherichia coli CIP 54127 as test strains. MIC determinations were carried out as a preliminary step, and relative growth intensity was used to describe the bacteriostatic activity of surface-active agents (Amonyl 380 BA, Amonyl 671 SB). In the study of combinations, results were interpreted with Fractional Inhibitory Concentration indexes and represented by isobolograms. A fair correlation was shown between the method of Berenbaum and the checkerboard titration method. Combinations between chlorhexidine, cetrimonium bromide and benzalkonium chloride were synergistic or additive; combinations of antiseptics and preservatives were generally not antagonistic. The methods were also well adapted to the study of interactions involving surface-active agents, a critical problem in the formulation of topical antimicrobial agents. PMID- 1447056 TI - Inhibition of Shigella sonnei by Lactobacillus casei and Lact. acidophilus. AB - The protective effect of feeding milk fermented with a mixture of Lactobacillus casei and Lact. acidophilus against Shigella sonnei was studied. There was a 100% survival rate in mice fed for 8 d with fermented milk and then dosed orally with Sh. sonnei. The survival rate in control mice was approximately 60% after 21 d. Colonization of the liver and spleen with Sh. sonnei was markedly inhibited by pretreatment with fermented milk. Differences in cell counts of 2-3 log units between treated and control mice were always obtained, shigellas were not detected in these organs by the 10th day in treated mice, while high levels were maintained in the controls. Higher levels of anti-shigella antibodies were found both in sera and in small intestinal fluid of mice treated with fermented milk, suggesting that the protective immunity could be mediated by the mucosal tissue. These results suggest that milk fermented with Lact. casei and Lact. acidophilus could be used as a prophylactic against gastrointestinal infections by shigellas. PMID- 1447057 TI - Contaminated marine wounds--the risk of acquiring acute bacterial infection from marine recreational beaches. AB - An animal model was used to determine the potential for causing wound infections of bacteria isolated from marine recreational beaches in Hong Kong. Water samples were characterized physically, chemically and bacteriologically and used to inoculate artificially-induced wounds in rats. Morbidity and mortality correlated significantly (P < 0.01) with MacConkey plate counts and faecal coliform counts (membrane filtration) and inversely with salinity of the water. The majority of deaths were due to infection caused by marine and estuarine bacteria rather then enteric organisms. A total of 318 bacterial strains was isolated from the wounds and blood of animals inoculated with seawater, of which 242 were marine/estuarine (predominantly Vibrio spp., Aeromonas hydrophila and Pseudomonas putrefaciens) and 40 were enterobacteria. The virulence of the animal strains were comparable with those from clinical sources. PMID- 1447058 TI - Identification and composition of the tonsillar and anal enterococcal and streptococcal flora of dogs and cats. AB - Enterococcus faecalis was the most frequently isolated enterococcal species from anal swabs and tonsils of dogs and cats, although in the anal samples from dogs Ent. hirae was found almost as often as Ent. faecalis. Most Ent. faecium strains from dog tonsils differed from those associated with humans and other animals in that they fermented sorbitol. Typical Ent. avium as well as atypical Ent. avium like strains were seen in dogs, while the related species Ent. raffinosus was associated with cat tonsils. Enterococcus cecorum also occurred mainly in cats. Certain atypical strains, presumptively identified as Ent. cecorum, shared characteristics with Ent. columbae. The most frequent streptococcal species in tonsils of cats and dogs were Streptococcus suis and Strep. canis. Streptococcus canis and Strep. bovis predominated in anal swabs. The canine Strep. suis differed from the common porcine strains in fermenting mannitol. Forty-seven of the 288 isolates examined could not be identified or related to known species. The characteristics of two groups of these bacteria, provisionally called 'Ton 31 group' and 'O7 group' are described. PMID- 1447059 TI - Analysis of polar lipids from some representative enterobacteria, Plesiomonas and Acinetobacter by fast atom bombardment-mass spectrometry. AB - Fast atom bombardment-mass spectrometry (FAB-MS) was used to analyse lipid extracts of bacteria to assess its usefulness for analysing anionic phospholipids of potential chemotaxonomic value. The following micro-organisms were tested: Acinetobacter calcoaceticus, Acinetobacter sp., Citrobacter freundii, Enterobacter cloacae (2 strains), Escherichia coli (3 strains), Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Plesiomonas shigelloides, Proteus mirabilis (3 strains), Serratia liquefaciens and Serratia marcescens. Negative-ion spectra provide data for twenty-seven major carboxylate anions (m/z 209-325) and for thirty-seven major phospholipid anions (m/z 645 774). Generally, the largest carboxylate peaks were due to 16:1, 16:0, cyc17 and 18:1 while the largest phospholipid anion peaks were due to PE(32:1), PE(33:1), PE(34:1), PE(34:2), PG(30:2), PG(31:2), PG(32:2), PG(34:1) and PS(33:0). However, quantitative differences were observed. For example, Acinetobacter lacked PE (33:1) but had exceptionally high peaks at m/z 748, PS(33:0), and m/z 281, octadecanoate. Unknown 'carboxylate' peaks were detected at m/z 254, 256, 261, 268, 282 and 301. In some cases, unknown peaks appeared to constitute possible homologous series being separated by delta m/z of 14(identical to methylene). For chemotaxonomic purposes, the complexity of the data required numerical analysis. Using the Pearson coefficient of linear correlation, as a measure of association, it was possible to compare all strains analysed. Typical results for strain comparisons were as follows: Ent. cloacae vs Ent. cloacae, r = 0.90 (Ent. cloacae vs Ac. calcoaceticus, r = 0.46). Thus FAB-MS represents an excellent means of obtaining large quantities of data on polar lipids of a range of bacterial isolates, which may be suitable for chemotaxonomic purposes. PMID- 1447060 TI - Characterization of bacteria by multiparameter flow cytometry. AB - An arc-lamp based flow cytometer was used to obtain high resolution measurements of the light scattering characteristics and DNA contents of eight different bacteria. Light scatter profiles of bacteria are a useful first step when flow cytometry is used to characterize organisms. Scanning and transmission electron microscopy of the bacterial samples demonstrate that the structural basis of the light scattering profiles is not always clear, i.e. some organisms appear to have anomalous light scattering characteristics. The use of a third measurement parameter, DNA content, allowed much better discrimination of the organisms. Flow cytometry shows great promise as a method for the rapid discrimination and identification of bacterial populations. PMID- 1447061 TI - Interpretation of EMG spectral alterations and alteration indexes at sustained contraction. AB - Alterations of the electromyographic power spectrum have been studied extensively to assess fatigue development in the neuromuscular system. Usually, a data reduction has been applied to create an index based on the mean power frequency or the median frequency. The physiological origin of the spectrum alterations has been (and to some extent still is) incompletely known. However, during the 1980s, substantial progress has been made in this field. The factors affecting the electromyographic power spectrum discussed in this review are action potential velocity decrease, firing statistics alterations, action potential modification, muscle temperature, additional recruitment at fatigue, and force level. Their impact on three commonly used fatigue indexes, mean power frequency, median frequency, and zero crossing rate, is also reviewed. PMID- 1447062 TI - Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion. AB - Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure-RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (+/- SE) increased from net reabsorption during control of 111 +/- 27 ml/h to net filtration of 1,219 +/- 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447063 TI - Effect of physical training on insulin response to intravenous glucose in male peripubertal rats. AB - This study was undertaken to evaluate the effects of regular endurance-type exercise (i.e., swimming) on glucose tolerance and glucose-stimulated insulin response (GSIR) in 55- and 90-day-old peripubertal male rats. Intravenous glucose tolerance tests (0.5 g/kg) were done in four groups of male Sprague-Dawley rats: two groups of trained (TR; 55- and 90-day-old) and two groups of age- and weight matched untrained (UNTR) rats. The UNTR rats were subjected to a continuous food restriction to maintain body weights equal to those of the TR rats. Rats were received in our laboratory after weaning at 21 days of age and were evaluated 48 h after the last exercise bout. No significant differences in body weights were found between TR and UNTR rats, at the age of either 55 or 90 days. A significant (P < 0.01) decrease in the mean integrated area under the glucose and insulin curves was observed in TR compared with UNTR groups in 55- as well as 90-day-old rats. These results indicate that exercise training in male rats improves the glucose tolerance and GSIR before and during puberty (21-90 days) independently of a reduction in body weight gain. PMID- 1447064 TI - Hypohydration affects forearm vascular conductance independent of heart rate during exercise. AB - Elevated body core temperature stimulates cutaneous vasodilation, which can be modified by nonthermal factors. To test whether hypohydration affects forearm vascular conductance discretely from relative alterations in heart rate (HR), eight trained cyclists exercised progressively for 20 min each at 60, 120, and 180 W [approximately 22, 37, and 55% of maximal cycling O2 consumption (VO2peak), respectively] in a warm humid environment (dry bulb temperature 30 degrees C; wet bulb temperature 24 degrees C). Esophageal temperature and forearm blood flow were measured every 30 s, and mean arterial pressure and HR were measured at rest and during each exercise intensity (minutes 15, 35, and 55). In the hypovolemic (HP) compared with the euvolemic (EU) state, blood volume was contracted by 24-h fluid restriction an average of 510 ml, and this difference was sustained throughout exercise. The esophageal temperature and HR responses were similar between EU and HP states at 60 and 120 W but were significantly (P < 0.05) higher in HP by the end of 180 W. In contrast, the forearm blood flow response was significantly (P < 0.05) depressed during exercise at 120 and 180 W in HP, whereas mean arterial pressure remained similar between conditions. When body core temperature is elevated in a hypohydrated state, forearm vascular conductance is reduced at exercise intensities of approximately 37% VO2peak, which is independent of relative changes in HR. These findings are consistent with the notion that during exercise an attenuated cutaneous vasodilation is elicited by alterations in regionalized sympathetic outflow, which is unaccompanied by activation of cardiac pacemaker cells. PMID- 1447065 TI - Estrogen replacement in middle-aged women: thermoregulatory responses to exercise in the heat. AB - Thermoregulatory, cardiovascular, and body fluid responses during exercise in the heat were tested in five middle-aged (48 +/- 2 yr) women before and after 14-23 days of estrogen replacement therapy (ERT). The heat and exercise challenge consisted of a 40-min rest period followed by semirecumbent cycle exercise (approximately 40% maximal O2 uptake) for 60 min. At rest, the ambient temperature was elevated from a thermoneutral (dry bulb temperature 25 degrees C; wet bulb temperature 17.5 degrees C) to a warm humid (dry bulb temperature 36 degrees C; wet bulb temperature 27.5 degrees C) environment. Esophageal (Tes) and rectal (Tre) temperatures were measured to estimate body core temperature while arm blood flow and sweating rate were measured to assess the heat loss response. Mean arterial pressure and heart rate were measured to evaluate the cardiovascular response. Blood samples were analyzed for hematocrit (Hct), hemoglobin ([Hb]), plasma 17 beta-estradiol (E2), progesterone (P4), protein, and electrolyte concentrations. Plasma [E2] was significantly (P < 0.05) elevated by ERT without affecting the plasma [P4] levels. After ERT, Tes and Tre were significantly (P < 0.05) depressed by approximately 0.5 degrees C, and the Tes threshold for the onset of arm blood flow and sweating rate was significantly (P < 0.05) lower during exercise. After ERT, heart rate during exercise was significantly lower (P < 0.05) without notable variation in mean arterial pressure. Isotonic hemodilution occurred with ERT evident by significant (P < 0.05) reductions in Hct and [Hb], whereas plasma tonicity remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447066 TI - Nocturnal variations in human lower leg subcutaneous blood flow related to sleep stages. AB - Nocturnal subcutaneous adipose tissue blood flow rate was measured in the lower legs of 10 normal human subjects together with systemic arterial blood pressure, heart rate, and registration of sleep stages under ambulatory conditions. The 133Xe washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used for measurement of blood flow rates. The sleep recordings were performed with a portable computerized sleep analysis system. In accordance with the results of previous studies, a hyperemic blood flow rate phase (mean increase 140%) for 100 min was observed approximately 60 min after the subjects went to bed. The moment of onset of the hyperemic phase was closely related to the moment of onset of the first episode of deep sleep (stages 3 and 4). There was a significant (P < 0.01) overrepresentation of deep sleep in the hyperemic phase compared with adjacent phases, and rapid-eye-movement sleep predominantly occurred in the latter part of the night, when the subcutaneous blood flow rate was stable. The results of the present study are in accordance with current theories of the interrelationship between the thermoregulatory and the arousal state control systems and, thus, might suggest that the nightly subcutaneous hyperemia represents a thermoregulatory effector mechanism. PMID- 1447067 TI - A second postcooling afterdrop: more evidence for a convective mechanism. AB - An attempt was made to demonstrate the importance of increased perfusion of cold tissue in core temperature afterdrop. Five male subjects were cooled twice in water (8 degrees C) for 53-80 min. They were then rewarmed by one of two methods (shivering thermogenesis or treadmill exercise) for another 40-65 min, after which they entered a warm bath (40 degrees C). Esophageal temperature (Tes) as well as thigh and calf muscle temperatures at three depths (1.5, 3.0, and 4.5 cm) were measured. Cold water immersion was terminated at Tes varying between 33.0 and 34.5 degrees C. For each subject this temperature was similar in both trials. The initial core temperature afterdrop was 58% greater during exercise (mean +/- SE, 0.65 +/- 0.10 degrees C) than shivering (0.41 +/- 0.06 degrees C) (P < 0.005). Within the first 5 min after subjects entered the warm bath the initial rate of rewarming (previously established during shivering or exercise, approximately 0.07 degrees C/min) decreased. The attenuation was 0.088 +/- 0.03 degrees C/min (P < 0.025) after shivering and 0.062 +/- 0.022 degrees C/min (P < 0.025) after exercise. In 4 of 10 trials (2 after shivering and 2 after exercise) a second afterdrop occurred during this period. We suggest that increased perfusion of cold tissue is one probable mechanism responsible for attenuation or reversal of the initial rewarming rate. These results have important implications for treatment of hypothermia victims, even when treatment commences long after removal from cold water. PMID- 1447068 TI - Catecholamines in turkeys with alcohol-induced cardiomyopathy. AB - Although alcoholic cardiomyopathy has been difficult to reproduce in animals, turkeys fed 5% ethanol develop a dilated congestive cardiomyopathy. We therefore used this model to examine the adrenergic response to left ventricular dysfunction induced by alcohol. In normal turkeys, norepinephrine in kidneys decreased markedly with age from 1 day to 2 mo, with a similar but less dramatic decrease in cardiac norepinephrine. By 2 mo, chronic alcohol ingestion depleted cardiac norepinephrine compared with controls (217 +/- 22 vs. 316 +/- 41 ng/g, P < 0.05), even though cardiac norepinephrine is relatively low in turkeys compared with many other animals and humans. Norepinephrine in aorta was also decreased with alcohol administration, but kidney norepinephrine was unaffected. Dopamine was unaltered in any of the organs studied. Plasma norepinephrine is normally high in turkeys with arterial levels greater than venous (2,898 +/- 746 vs. 1,987 +/- 531 pg/ml at 2 mo). Venous plasma norepinephrine did not differ from control (2,595 +/- 547 pg/ml) after 2 mo of alcohol. Thus, as in humans, cardiomyopathy in alcohol-fed turkeys is associated with reduced cardiac norepinephrine, but unlike humans with cardiomyopathy, circulating norepinephrine remains normal. PMID- 1447069 TI - Tracheal blood flow and luminal clearance of 99mTc-DTPA in sheep. AB - Tracheal blood flow and 99mTc-labeled diethylenetriamine pentaacetic acid (DTPA) clearance were measured in the sheep trachea in vivo. The tracheal arteries were isolated and perfused. An isolated segment of tracheal lumen was filled with Krebs-Henseleit solution containing 99mTc-DTPA, and radioactivity was measured in blood from a catheterized tracheal vein. Infusions at constant pressure of methacholine (n = 5), albuterol (n = 6), and histamine (n = 5) increased arterial inflow [+250 +/- 73.0, +74.2 +/- 22.9, +68.9 +/- 39.2% (SE), respectively] and venous outflow (+49.5 +/- 13.8, +11.6 +/- 4.5, +6.2 +/- 13.9%) but decreased 99mTc-DTPA output (-36.8 +/- 8.4, -20.4 +/- 6.2, -58.1 +/- 11.7%) and concentration (-53.9 +/- 10.1, -27.3 +/- 7.5, -49.3 +/- 14.4%). Phenylephrine (n = 9) decreased arterial inflow (-49.4 +/- 10.0%) and venous outflow (-4.1 +/- 5.9%) but increased 99mTc-DTPA output (+74.6 +/- 44.2%) and concentration (+94.4 +/- 56.6%). When the tracheal arteries were initially perfused at constant flow and the flow rate was then changed, 50% increases in flow (n = 5) increased perfusion pressure (+35.9 +/- 2.2%) and venous outflow (+10.5 +/- 3.8%) but decreased 99mTc-DTPA output (-24.4 +/- 7.8%) and concentration (-30.4 +/- 8.8%). Decreases in flow of 50% (n = 3) and 100% (n = 10) decreased perfusion pressure ( 34.2 +/- 4.2, -80.1 +/- 3.5%, respectively) and venous outflow (-11.0 +/- 4.8, 29.7 +/- 7.2%) but increased 99mTc-DTPA output (+45.9 +/- 27.5, +167.4 +/- 70.4%) and concentration (+64.7 +/- 26.7, +305.7 +/- 110.2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447071 TI - Potassium and ventilation during incremental exercise in trained and untrained men. AB - The present investigation was undertaken to examine the relationship between plasma potassium (K+) and ventilation (VE) during incremental exercise. Blood lactate (La-) was also measured, and its relationship with VE was similarly examined. Eight endurance-trained triathletes (ET) and eight active but untrained men (UT) performed an incremental cycling test to volitional fatigue. Maximal oxygen uptake (VO2max) and oxygen uptake (VO2) at lactate threshold (LT) were higher (P < 0.05) in ET (VO2max 4.60 +/- 0.10 l/min, LT 2.77 +/- 0.85 l/min) than in UT (VO2max 3.79 +/- 0.11 l/min, LT 1.94 +/- 0.60 l/min). There were significant (P < 0.05) correlations between VE and K+ (UT 0.87, ET 0.77) and between VE and La- (UT 0.88, ET 0.85). In ET compared with UT, VE was lower (P < 0.05) at 330 W, K+ was lower at 300 and 330 W, and La- was lower at all work loads > 90 W. These results suggest that K+ may make an important contribution to the regulation of ventilation during incremental exercise and that endurance training attenuates the K+ response to that exercise. PMID- 1447070 TI - Myosin heavy chain composition in the rat diaphragm: effect of age and exercise training. AB - Increases in aerobic capacity in both young and senescent rats consequent to endurance exercise training are now known to occur not only in locomotor skeletal muscle but also in diaphragm. In the current study the effects of aging and exercise training on the myosin heavy chain (MHC) composition were determined in both the costal and crural diaphragm regions of female Fischer 344 rats. Exercise training [treadmill running at 75% maximal oxygen consumption (1 h/day, 5 day/wk, x 10 wk)] resulted in similar increases in plantaris muscle citrate synthase activity in both young (5 mo) and old (23 mo) trained animals (P < 0.05). Computerized densitometric image analysis of fast and slow MHC bands revealed the ratio of fast to slow MHC to be significantly higher (P < 0.005) in the crural compared with costal diaphragm region in both age groups. In addition, a significant age-related increase (P < 0.05) in percentage of slow MHC was observed in both diaphragm regions. However, exercise training failed to change the relative proportion of slow MHC in either the costal or crural region. PMID- 1447072 TI - Effect of a regional increase in alveolar pressure on pulmonary blood flow. AB - We examined whether wedging a catheter (0.5 cm OD) into a subsegmental airway in dog (n = 6) or pig lungs (n = 5) and increasing pressure in the distal lung segment affected pulmonary blood flow. Dogs and pigs were anesthetized and studied in the prone position. Pulmonary blood flow was measured by injecting radiolabeled microspheres (15 microns diam) into the right atrium when airway pressure (Pao) was 0 cmH2O and pressure in the segment distal to the wedged catheter (Ps) was 0, 5, or 15 cmH2O and when Pao = Ps = 15 cmH2O. The lungs were excised, air-dried, and sectioned. Blood flow per gram dry weight normalized to cardiac output to the right or left lung, as appropriate, was calculated for the test segment, a control segment in the opposite lung corresponding anatomically to the test segment, the remainder of the lung containing the test segment (test lung), and the remainder of the lung containing the control segment (control lung). The presence of the catheter reduced blood flow in the test segment compared with that in the control segment and in the test lung. Blood flow was not affected by increasing pressure in the test segment. We conclude that, in studies designed to measure collateral ventilation in dog lungs, the presence of the wedged catheter is likely to have a greater effect on blood flow than the increase in pressure associated with measuring collateral airway resistance. PMID- 1447073 TI - Stress relaxation of the respiratory system in developing piglets. AB - To characterize the effect of postnatal development on the viscoelastic behavior of the respiratory system, we quantified the amplitude and time course of stress relaxation in the lungs and chest wall of seven newborn and eight 8-wk-old anesthetized piglets. Stress relaxation was distinguished from other dissipative pressure losses by performing airway occlusions at various constant inspiratory flows and fitting the pressure decays that ensue during the occlusions to a double-exponential function. We found that the amplitude of stress relaxation related linearly to the increase in elastic recoil (and, by extension, in the volume) of the lungs, chest wall, and respiratory system during the inflations preceding the occlusions. On the average, the slope of this relationship was 38 44% lower in the 8-wk-old than in the newborn piglets for the lungs and was not different for the chest wall. The time course of stress relaxation, expressed as a time constant, was not influenced by age. Our results indicate that respiratory system viscoelasticity is sensitive to the geometric and structural changes experienced by the lungs during the period of rapid somatic growth that follow birth in most mammals. PMID- 1447074 TI - Clearance of different-sized proteins from the alveolar space in humans and rabbits. AB - Investigation of the clearance of proteins from the air spaces is important for an understanding of the resolution of pulmonary edema and also because of current interest in delivery of therapeutic peptides via the distal air spaces. Few experimental studies have examined the size dependence for alveolar clearance of large macromolecules; there have been no human studies. In anesthetized rabbits, we measured clearance of cyanocobalamin and different-sized human proteins instilled into the air spaces. After 8 h, the amounts of instilled tracer recovered in the lungs were [57Co]cyanocobalamin, 19.4 +/- 3.0% (Stokes radius 0.65 nm); 125I-labeled insulin, 64.6 +/- 3.9% (1.2 nm); 131I-labeled albumin, 87.0 +/- 4.0% (3.5 nm); and 125I-labeled immunoglobulin G, 91.8 +/- 3.3% (5.5 nm) (P < 0.05). Sieving of different-sized proteins occurred across the alveolar epithelial barrier because tracer concentrations in air space lavage fluid after 8 h were decreased more for the smaller tracers than the larger ones. Size selectivity for alveolar protein clearance in humans with resolving alveolar edema was investigated by measuring the changes in albumin and total protein concentration. The fraction of total protein concentration made up of albumin was greater in the edema fluid than in the plasma initially. The albumin fraction decreased with time in 9 of 10 patients with resolving edema, from 0.62 +/- 0.2 to 0.58 +/- 0.10 (P < 0.05) after 10 +/- 5 h. Thus both rabbit studies and human studies provide evidence for size-dependent clearance of protein from the air spaces of the lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447075 TI - Retrofacial lesions: effects on CO2-sensitive phrenic and sympathetic nerve activity. AB - We made unilateral chemical (10- or 50-nl microinjections; 4.7 mM kainic acid) or electrolytic (5-15 mA; 15 s) lesions in a region of the rostral ventrolateral medulla (VLM) caudal to the retrotrapezoid nucleus in 10 decerebrate, paralyzed, vagotomized, and servo-ventilated cats. The lesions were 3.0-4.2 mm lateral to the midline, within 2 mm caudal to the facial nucleus, and within 2.5 mm of the VLM surface. Four control injections (mock cerebrospinal fluid and fluorescent beads alone) produced small and inconsistent effects over 3-5 h. The predominant effect of the lesions was a significant decrease in baseline integrated phrenic nerve amplitude (PNA) (apnea in 2 cases), total respiratory cycle duration, and the response to increased CO2 (slope < 15% of control in 3 cases). The respiratory-related peak amplitude of the integrated sympathetic signal, blood pressure, and the sympathetic nerve activity response to CO2 were also decreased after the majority of lesions. Not all lesions produced all effects, and some lesions resulted in increased PNA and respiratory cycle duration. The lesioned region appears functionally to represent a caudal extension of the retrotrapezoid nucleus containing neurons necessary for normal baseline PNA and CO2 sensitivity. In addition, it contains neurons involved in the determination of resting respiratory frequency and normal sympathetic activity and blood pressure. The pattern of mixed responses among animals suggests that a heterogeneity of function is present within a relatively small VLM region. PMID- 1447076 TI - Pretreatment with catalase or dimethyl sulfoxide protects alloxan-induced acute lung edema in dogs. AB - We tested the preventive effects of catalase, an enzymatic scavenger of hydrogen peroxide, or dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, on intravenous alloxan-induced lung edema in four groups of pentobarbital sodium anesthetized, ventilated dogs for 3 h: saline (20 ml.kg-1.h-1) infusion alone (n = 5), alloxan (75 mg/kg) + saline infusion (n = 5), catalase (150,000 U/kg) + alloxan + saline infusion (n = 5), or DMSO (4 mg/kg) + alloxan + saline infusion (n = 5). Catalase or DMSO significantly prevented the increase in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha over 3 h after alloxan and the accumulation of extravascular lung water after 3 h [3.95 +/- 0.52 (SE) g/g with catalase, 3.06 +/- 0.42 g/g with DMSO] but not early pulmonary arterial pressor response. An electron microscopic study indicated that catalase or DMSO significantly reduced the endothelial cellular damages after alloxan. These findings strongly suggest that hydrogen peroxide and hydroxyl radical are major mediators responsible for intravenous alloxan-induced edematous lung injury in anesthetized ventilated dogs. PMID- 1447077 TI - Oxidation of exogenous medium-chain free fatty acids during prolonged exercise: comparison with glucose. AB - The purpose of this study was to compare the oxidation rate of exogenous 13C labeled medium-chain triacylglycerols (MCT) with that of an isocaloric amount of exogenous [13C]glucose and to evaluate their respective effects on endocrine and metabolic responses to moderate prolonged exercise. To take into account changes in isotopic composition of 13CO2 arising from oxidation of endogenous substrates because of exercise and/or substrate ingestion that overestimates the oxidation rate of exogenous substrates, two levels of 13C enrichment were used for each substrate. Six young healthy males (20-26 yr of age) completed five 2-h periods of exercise at 65 +/- 3% maximal O2 uptake (VO2max) on a cycle ergometer at 7-day intervals: one control exercise with water ingestion, two trials with ingestion of 25 g of [13C]MCT (trioctanoate) 1 h before exercise, and two trials with 57 g of [13C]glucose (dissolved in 1,000 ml of water) ingested during exercise. Exogenous MCT and glucose began to be oxidized within the first 30 min of exercise, and the oxidation rate increased progressively until the end of exercise for both substrates. Over the 2-h period of exercise, 13.6 +/- 3.5 g of ingested MCT and 36.4 +/- 8.2 g of exogenous glucose were oxidized, which represent 54 and 64%, respectively, of the total amount ingested. The contribution of MCT (119 +/- 31 kcal) and glucose (140 +/- 36 kcal) was not significantly different and represented 7 and 8.5%, respectively, of the total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447078 TI - Influence of graded dehydration on hyperthermia and cardiovascular drift during exercise. AB - This investigation determined the effect of different rates of dehydration, induced by ingesting different volumes of fluid during prolonged exercise, on hyperthermia, heart rate (HR), and stroke volume (SV). On four different occasions, eight endurance-trained cyclists [age 23 +/- 3 (SD) yr, body wt 71.9 +/- 11.6 kg, maximal O2 consumption 4.72 +/- 0.33 l/min] cycled at a power output equal to 62-67% maximal O2 consumption for 2 h in a warm environment (33 degrees C dry bulb, 50% relative humidity, wind speed 2.5 m/s). During exercise, they randomly received no fluid (NF) or ingested a small (SF), moderate (MF), or large (LF) volume of fluid that replaced 20 +/- 1, 48 +/- 1, and 81 +/- 2%, respectively, of the fluid lost in sweat during exercise. The protocol resulted in graded magnitudes of dehydration as body weight declined 4.2 +/- 0.1, 3.4 +/- 0.1, 2.3 +/- 0.1, and 1.1 +/- 0.1%, respectively, during NF, SF, MF, and LF. After 2 h of exercise, esophageal temperature (Tes), HR, and SV were significantly different among the four trials (P < 0.05), with the exception of NF and SF. The magnitude of dehydration accrued after 2 h of exercise in the four trials was linearly related with the increase in Tes (r = 0.98, P < 0.02), the increase in HR (r = 0.99, P < 0.01), and the decline in SV (r = 0.99, P < 0.01). LF attenuated hyperthermia, apparently because of higher skin blood flow, inasmuch as forearm blood flow was 20-22% higher than during SF and NF at 105 min (P < 0.05). There were no differences in sweat rate among the four trials. In each subject, the increase in Tes from 20 to 120 min of exercise was highly correlated to the increase in serum osmolality (r = 0.81-0.98, P < 0.02-0.19) and the increase in serum sodium concentration (r = 0.87-0.99, P < 0.01-0.13) from 5 to 120 min of exercise. In summary, the magnitude of increase in core temperature and HR and the decline in SV are graded in proportion to the amount of dehydration accrued during exercise. PMID- 1447079 TI - Theoretical analysis of occlusion techniques for measuring pulmonary capillary pressure. AB - We have developed a model including three serial compliant compartments (arterial, capillary, and venous) separated by two resistances (arterial and venous) for interpreting in vivo single pulmonary arterial or venous occlusion pressure profiles and double occlusion. We formalized and solved the corresponding system of equations. We showed that in this model 1) pulmonary capillary pressure (Pc) profile after arterial or venous occlusion has an S shape, 2) the estimation of Pc by zero time extrapolation of the slow component of the arterial occlusion profile (Pcao) always overestimates Pc, 3) symmetrically such an estimation on the venous occlusion profile (Pcvo) always underestimates Pc, 4) double occlusion pressure (Pcdo) differs from Pc. We evaluated the impact of varying parameter values in the model with parameter sets drawn either from the literature or from arbitrary arterial and venous pressures, being respectively 20 and 5 mmHg. Resulting Pcao-Pc differences ranged from 0.4 to 5.4 mmHg and resulting Pcvo-Pc differences ranged from -0.3 to -5.0 mmHg. Pcdo Pc was positive or negative, its absolute value in general being negligible (< 1.1 mmHg). PMID- 1447080 TI - Effect of the pericardium on atrial systolic function. AB - The effect of pericardial constraint on atrial systolic function was investigated in nine acutely instrumented anesthetized dogs. Left and right atrial pressures were recorded by high-fidelity catheters; auricular diameters and free wall segment lengths were measured by sonomicrometry. Atrial function curves were constructed by relating atrial systolic dimensional shortening to atrial end diastolic pressure during progressive volume loading. With the pericardium closed, the function curves were shifted markedly downward and rightward, such that atrial systolic shortening was reduced at any given pressure. There was a concomitant leftward and upward shift of the atrial end-diastolic pressure dimension relationship. The relationship between atrial systolic shortening and atrial end-diastolic dimension was not shifted. These results suggest that the apparent depression of atrial systolic function with the pericardium closed is due to a restrictive effect of the pericardium on atrial filling. In conclusion, in the acutely dilated heart, the pericardium restricts atrial filling and thus causes a reduction in atrial systolic contribution to ventricular filling. PMID- 1447081 TI - Effects of simulated microgravity (HDT) on blood fluidity. AB - Exposures to microgravity and head-down tilt (HDT) produce similar changes in body fluid. This causes an increase in hematocrit that significantly affects hemorheological values. Lack of physical stimulation under bed rest conditions and the relative immobility of the crew during spaceflight also affects the blood fluidity. A group of six healthy male subjects participated as volunteers, and blood samples were collected 10 days before, on day 2 and day 9, and 2 days after the HDT phase. Blood rheology was quantified by plasma viscometry, red cell aggregability, and red cell deformability. A reduced red cell deformability, an indication of the diminished quality of the red blood cells, was measured under HDT conditions that finally led to the so-called "space flight anemia." Enhanced red cell membrane fragility induced by diminished physical activity and an increase in hemoglobin concentration are responsible for this effect. Plasma viscosity is reduced as a result of diminished plasma proteins. However, despite the reduction in plasma proteins, including fibrinogen, alpha 2-macroglobulin, and immunoglobulin M, red cell aggregation was enhanced, principally because of the increase in hematocrit. Our results of hemorheological alterations under HDT conditions may help to elucidate the formerly documented hematologic changes during spaceflight. PMID- 1447082 TI - Effect of zymosan-activated plasma on the deformability of rabbit polymorphonuclear leukocytes. AB - Intravascular infusion of inflammatory mediators causes a sudden neutropenia due to the sequestration of polymorphonuclear leukocytes (PMN) within the microvasculature of the lung and other organs. This sequestration could be due to a decrease in the ability of PMN to deform and pass through the narrow capillary bed. The purpose of this study was to determine if the complement fragments present in zymosan-activated plasma (ZAP) caused a rapid stiffening of PMN. The PMN deformability was determined by measuring the pressure required to pass PMN through a polycarbonate filter containing 5-micron pores at a constant flow rate as well as the extraction of PMN compared with red blood cells and 125I-labeled albumin by the filter. The role of the cytoskeleton in PMN deformation was examined in studies where F-actin formation was inhibited using cytochalasin B or microtubule assembly was inhibited using colchicine. The results showed that treatment with ZAP induced a rapid decrease in PMN deformability. Inhibiting the formation of F-actin made the unstimulated PMN more deformable and reduced the stiffening induced by ZAP. In contrast, inhibition of microtubule reassembly did not alter either normal deformability or the ZAP-induced decrease in deformability. In vivo, colchicine increased normal PMN margination but did not inhibit the rapid sequestration of PMN induced by infusion of ZAP. These studies indicate that ZAP induces a rapid decrease in PMN deformability that is mediated through the cytoskeleton. They suggest that this decrease is due to the polymerization of F-actin. PMID- 1447083 TI - Hypoxia-induced downregulation of beta-adrenergic receptors in rat heart. AB - To test the desensitization hypothesis of cardiac beta-adrenergic receptors (beta AR) in chronic hypoxia, the effect of 1, 3, 7, 15, and 21 days of exposure to hypobaric hypoxia (380 Torr) was evaluated in Wistar rats. Exposure to hypoxia for 1-15 days did not induce any change in right and left ventricular beta-AR density (Bmax) determined with [125I]iodocyanopindolol or in antagonist affinity. After 21 days, Bmax decreased by 24% in the left ventricle. In contrast, no change in beta-AR was shown in the right hypertrophied ventricle. Agonist affinity in the left ventricle was not altered, as shown by the analysis of displacement curves of isoproterenol (normoxia 185 +/- 26 nM, hypoxia 170 +/- 11 nM). Moreover, there was no significant decrease in adenylate cyclase activity (pmol.mg-1.min-1) in the left ventricle. In the right ventricle, a 21-day exposure to hypoxia led to a decrease in basal and maximal activity when stimulated by isoproterenol. A decrease in tissue norepinephrine content was observed after 7 days of hypoxia. In conclusion, these data support the beta-AR downregulation hypothesis as one of the mechanisms of myocardial adaptation to high altitude occurring after 2-3 wk of exposure to hypoxia. The regulation pathways of beta-AR may differ between left nonhypertrophied and right hypertrophied ventricles. No evidence of profound abnormality of signal transduction was shown. PMID- 1447084 TI - Cytokine immunoreactivity in plasma does not change after moderate endurance exercise. AB - We investigated whether increased concentrations of circulating cytokines may be responsible for exercise-induced priming of blood neutrophils (J. A. Smith et al. Int. J. Sports Med. 11: 179-187, 1990). The plasma concentrations of tumor necrosis factor-alpha, interleukin- (IL) 1 beta, IL-6, granulocyte-macrophage colony-stimulating factor, and neopterin in trained and untrained human subjects were measured by immunoassay before and after 1 h of cycling at 60% of maximal oxygen uptake. C-reactive protein and creatine kinase (CK) were also measured before and 24 h after exercise as markers of the "acute-phase response" and muscle damage (C. Taylor et al. J. Appl. Physiol. 62: 464-469, 1987), respectively. The small changes in the plasma concentrations of cytokines or neopterin observed after exercise in both trained and untrained subjects were not significantly different to those found in a control group of nonexercised subjects. However, untrained subjects did exhibit an acute-phase response (P = 0.04) 24 h after exercise without additional release of CK into plasma. Baseline training differences were confined to a twofold elevation in CK activity (P = 0.04). The results show that circulating cytokines are unlikely to be responsible for the priming of neutrophil microbicidal activity observed after moderate endurance exercise (J. A. Smith et al. Int. J. Sports Med. 11: 179-187, 1990). PMID- 1447085 TI - Effect of bilateral vagotomy on oxygenation, arousal, and breathing movements in fetal sheep. AB - To investigate the effects of bilateral cervical vagotomy on arousal and breathing responses, we studied eight sham-operated and eight chronically instrumented unanesthetized vagotomized sheep fetuses between 136 and 144 days of gestation (term approximately 147 days). Each fetus was instrumented to record sleep states, diaphragmatic electromyogram, blood pressure, pH, and blood gas tensions. In a randomized order, fetal lungs were distended with four different O2 concentrations: 0 (100% N2), 21, 50, and 100% at a continuous positive airway pressure of 30 cmH2O via an in situ Y-endotracheal tube. Under control conditions, inspiratory time and the duration of the single longest breathing episode decreased from 598 +/- 99 (SD) ms and 24 +/- 10 min in sham group to 393 +/- 162 ms and 11.0 +/- 3.0 min in vagotomized group (P = 0.04 and 0.033), respectively. In response to lung distension with 100% N2, breathing time decreased from 44 +/- 17 to 20 +/- 18% (P = 0.045) in sham-operated fetuses, whereas it remained unchanged in the vagotomized group. In response to 100% O2, fetal arterial PO2 increased in five of eight fetuses sham-operated from 18.2 +/- 5.1 to 227 +/- 45 Torr (P = 0.0001) and in six of eight vagotomized fetuses from 18.5 +/- 4.4 to 172 +/- 39 Torr (P < 0.001). Although arousal was observed in all oxygenated fetuses at the onset of breathing, the duration of arousal was markedly attenuated in vagotomized fetuses (14 +/- 10 vs. 46 +/- 29 min in sham group; P = 0.024). Frequency and amplitude of breathing and respiratory output (frequency x amplitude) increased only in sham group (P = 0.02, 0.004, and 0.0002, respectively). We conclude that in response to lung distension and oxygenation, arousal and stimulation of breathing during active and quite sleep are critically dependent on intact vagal nerves. PMID- 1447086 TI - Effects of catecholamines and potassium on cardiovascular performance in the rabbit. AB - Resting subjects risk cardiac arrest if plasma potassium ([K+]p) is raised rapidly to 7-9 mM, but brief bouts of exhaustive exercise in healthy subjects can give similar [K+]p without causing cardiac problems. We investigated the effects of [K+]p and catecholamines on systolic blood pressure (SBP) and mean aortic flow (MAF) in anesthetized rabbits and on maximum output pressure (MOP) in isolated working rabbit hearts. In six rabbits, hyperkalemia (11.4 +/- 0.4 mM) caused a fall in SBP from 116 +/- 6 to 49 +/- 6 mmHg and in MAF from 373 +/- 30 to 181 +/- 53 ml/min (P < 0.01). Raising [K+]p (11.6 +/- 0.3 mM) with norepinephrine (NE) (1.3 micrograms.kg-1.min-1 iv), however, increased SBP from 108 +/- 7 to 150 +/- 6 mmHg (P < 0.01) and MAF from 347 +/- 42 to 434 +/- 35 ml/min (P < 0.01). In 19 isolated working hearts, perfusion with 8 mM K+ Tyrode and then 12 mM K+ Tyrode reduced MOP from 87 +/- 3 (control 4 mM K+) to 67 +/- 3 (8 mM K+) and 51 +/- 2 cmH2O (12 mM K+) (P < 0.01); 12 mM K+ Tyrode with 0.08 microM NE or epinephrine, however, increased MOP from 67 +/- 6 (in 8 mM K+) to 85 +/- 6 cmH2O (NE) and from 58 +/- 2 to 76 +/- 5 cmH2O (epinephrine) (P < 0.01). Catecholamines may therefore play a key role in protecting the heart from exercise-induced hyperkalemia. PMID- 1447087 TI - Continuous measurement of Na concentration in CSF during gastric water infusion in dehydrated rats. AB - To assess the differential stimulus to central and intravascular osmoreceptors during recovery from thermal dehydration, we measured Na concentrations in cerebrospinal fluid ([Na]CSF) and plasma ([Na]p) continuously and compared these during simulated drinking by gastric water infusion (INF) in euhydrated and thermally dehydrated rats under anesthesia. Continuous measurement of [Na]CSF was obtained with a double-barreled Na electrode placed in the lateral ventricle. Continuous measurement of [Na]p was obtained from a flow cell Na electrode in an extracorporeal shunt. Measurements were made during 10 min of INF (2.5 ml/100 g body wt) into the stomach and during 20 min of recovery. Changes in [Na]CSF always lagged behind those in [Na]p and were quantitatively smaller after INF. The decrease in [Na]CSF occurred sooner in dehydrated than in euhydrated rats in response to the decrease in [Na]p (P < 0.01). These results suggest that water and/or Na movement between blood and CSF is accelerated during restitution from thermal dehydration, acting to prevent overhydration during the early phase of rehydration. PMID- 1447088 TI - Developmental changes in sequential activation of laryngeal abductor muscle and diaphragm in infants. AB - In animals and human adults, upper airway muscle activity usually precedes inspiratory diaphragm activity. We examined the interaction of the posterior cricoarytenoid muscle (PCA), which abducts the larynx, and the diaphragm (DIA) in the control of airflow in newborn infants to assess the effect of maturation on respiratory muscle sequence. We recorded tidal volume, airflow, and DIA and PCA electromyograms (EMG) in 12 full-term, 14 premature, and 10 premature infants with apnea treated with aminophylline. In most breaths, onset of PCA EMG activity preceded onset of DIA EMG activity (lead breaths). In all subjects, we also observed breaths (range 6-61%) in which PCA EMG onset followed DIA EMG onset (lag breaths). DIA neural inspiratory duration and the neuromechanical delay between DIA EMG onset and inspiratory flow were longer in lag than in lead breaths (P < 0.05 and P < 0.01, respectively). The frequency of lag breaths was greater in the premature infants [33 +/- 4% (SE)] than in either the full-term infants (21 +/- 3%, P < 0.03) or the premature infants with apnea treated with aminophylline (16 +/- 2%, P < 0.01). We conclude that the expected sequence of onset of PCA and DIA EMG activity is frequently disrupted in newborn infants. Both maturation and respiratory stimulation with aminophylline improve the coordination of the PCA and DIA. PMID- 1447089 TI - A new animal model for modulating myosin isoform expression by altered mechanical activity. AB - The purpose of this study was to develop a new rodent model that is capable of delineating the importance of mechanical loading on myosin heavy chain (MHC) isoform expression of the plantar and dorsi flexor muscles of the ankle. The essential components of this system include 1) stimulating electrodes that are chronically implanted into a muscle, allowing for the control of the activation pattern of the target muscle(s); 2) a training apparatus that translates the moment of the ankle into a linear force; and 3) a computer-controlled Cambridge 310 ergometer. The isovelocity profile of the ergometer ensured that the medial gastrocnemius (MG) produced forces that were > 90% of maximal isometric force (Po), and the eccentric contractions of the tibialis anterior (TA) were typically 120% of Po. Both the concentric and eccentric training programs produced statistically significant increases in the muscle mass of the MG (approximately 15%) and TA (approximately 7%) as well as a decrease in myofibrillar adenosinetriphosphatase activity. Both the white and red regions of the MG and TA exhibited significant increases in the relative content of the type IIa MHC and concomitant decreases in type IIb MHC expression. Although the red regions of the MG and red TA contained approximately 10% type I MHC, the training programs did not affect this isoform. It appears that when a fast-twitch muscle is stimulated at a high frequency (100 Hz) and required to contract either concentrically or eccentrically under high loading conditions, the expression of the type IIa MHC isoform will be upregulated, whereas that of the type IIb MHC will be concomitantly downregulated. PMID- 1447090 TI - Reliability of extravascular lung thermal volume measurements by thermal conductivity technique in sheep. AB - We tested the accuracy, sensitivity, and reproducibility of a new lung water computer, based on the thermal conductivity technique, in 22 anesthetized closed chest ventilated sheep with different treatments: 1) controls (n = 8), 2) 0.05 ml/kg of oleic acid + 100 ml/kg of lactated Ringer solution (n = 6), and 3) airway instillation of saline [3.1 +/- 1.3 (SD) g/kg, n = 8]. After 4 h, we determined the extravascular lung water gravimetrically. We found a significant overall correlation between the final extravascular lung thermal volume and the gravimetric extravascular lung mass (P < 0.001). Although the average ratio of extravascular lung thermal volume to extravascular lung mass was 0.97 +/- 0.25 ml/g for all groups, the computer overestimated extravascular lung mass in controls by 10% (17 g) and underestimated it in sheep with oleic acid by 15% (95 g) and in sheep with airway instillation by 8% (37 g). The computer also underestimated the small quantities of saline placed via the airway in the alveolar space by 75% (61 g). Reproducibility of three consecutive measurements was 4.3% (SE). We conclude that the thermal conductivity technique has an ability to detect the baseline extravascular lung mass but has a poor ability to detect an accurate increment of the extravascular lung water under poor tissue perfusion in anesthetized ventilated sheep. PMID- 1447091 TI - Turnover of hyaluronan in the rabbit pleural space. AB - Hyaluronan influences lung fluid balance. The clearance of lung hyaluronan by way of the pulmonary lymphatics and the pleural space is increased when fluid flux into the interstitium is increased. The purpose of this study was to determine the rate at which hyaluronan is removed from the pleural space. We injected hyaluronan, labeled with tritium in the acetyl group, into the pleural space of six rabbits. The appearance of [3H]H2O in serum was measured over time to calculate the turnover rate of hyaluronan. We found that the half-lives ranged between 8 and 15 h and were positively related to the amount of hyaluronan injected. At the end of the experiment, the contralateral pleural space was irrigated to determine the amount of pleural space hyaluronan, which was 0.3 micrograms/kg body wt. PMID- 1447092 TI - Postnatal development of the denervated lung in normoxia, hypoxia, or hyperoxia. AB - We asked whether lung innervation was essential for the normal postnatal development of the lung in conditions of normoxia, hypoxia, or hyperoxia. Litters of newborn rats were assigned to a normoxic [inspired oxygen partial pressure (PIO2) = 150 Torr, eight litters], hypoxic (PIO2 = 100 Torr, nine litters), or hyperoxic (PIO2 = 360 Torr, nine litters) group. Each litter consisted of 12 pups. Two days after birth, one-third of the litter had the vagus and sympathetic trunk cut in the neck on the left side [left denervated (L)], one-third was denervated on the right side (R), and one-third was sham-operated (S). From day 3, all pups were exposed to the designed PIO2, until day 8 or days 21-22. Almost all rats, whether S, R, or L, survived in normoxia and hyperoxia, whereas in hypoxia survival at day 22 of R and L was approximately 60-65%. Body growth was the same in S, R, and L and less in hypoxia than in normoxia or hyperoxia. At days 8 and 22, hematocrit and hemoglobin concentration, heart and lung dry and wet weights, and lung DNA content did not differ among S, R, and L, whether the pups were raised in normoxia, hypoxia, or hyperoxia. At days 21-22, aerobic metabolism and breathing pattern, both measured during air breathing, as well as compliance of isolated lungs, were also similar among S, R, and L for each of the conditions in which the pups were raised.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447093 TI - Pulmonary vascular reactivity and hemodynamic changes in elastase-induced emphysema in hamsters. AB - Changes in pulmonary hemodynamics and vascular reactivity in emphysematous hamsters were studied in an isolated lung preparation perfused at constant flow with blood and 3% dextran. Hamsters were treated with intratracheal porcine pancreatic elastase at 70 days of age, and experimental studies were conducted at 1, 3, and 8 mo after treatment. Baseline pulmonary arterial pressure in elastase treated lungs was increased compared with saline-treated control lungs 1 mo after treatment, but this increase did not progress at 3 and 8 mo. Increases in pulmonary arterial pressure in elastase-treated lungs were temporally correlated with the morphological development of emphysema and right ventricular hypertrophy; both of these were evident at 1 mo after treatment and showed little change thereafter. Pressor responses to hypoxia and angiotensin II were not different between elastase-treated and control lungs at 1 and 3 mo. At 8 mo, however, pressor responses in emphysematous lungs to 0% O2 (but not to angiotensin II) were significantly increased. This was the result of a lack of the normal age-related fall in the hypoxic pressor response. Our results suggest that the right ventricular hypertrophy found in these emphysematous animals results from a chronically increased pulmonary vascular resistance. Furthermore, increases in pulmonary vascular resistance in the early development of emphysema are likely a result of the loss of vascular beds and supporting connective tissue. PMID- 1447094 TI - Mechanical properties of human bronchial smooth muscle in vitro. AB - The in vitro mechanical properties of smooth muscle strips from 10 human main stem bronchi obtained immediately after pneumonectomy were evaluated. Maximal active isometric and isotonic responses were obtained at varying lengths by use of electrical field stimulation (EFS). At the length (Lmax) producing maximal force (Pmax), resting tension was very high (60.0 +/- 8.8% Pmax). Maximal fractional muscle shortening was 25.0 +/- 9.0% at a length of 75% Lmax, whereas less shortening occurred at Lmax (12.2 +/- 2.7%). The addition of increasing elastic loads produced an exponential decrease in the shortening and velocity of shortening but increased tension generation of muscle strips stimulated by EFS. Morphometric analysis revealed that muscle accounted for 8.7 +/- 1.5% of the total cross-sectional tissue area. Evaluation of two human tracheal smooth muscle preparations revealed mechanics similar to the bronchial preparations. Passive tension at Lmax was 10-fold greater and maximal active shortening was threefold less than that previously demonstrated for porcine trachealis by us of the same apparatus. We attribute the limited shortening of human bronchial and tracheal smooth muscle to the larger load presumably provided by a connective tissue parallel elastic component within the evaluated tissues, which must be overcome for shortening to occur. We suggest that a decrease in airway wall elastance could increase smooth muscle shortening, leading to excessive responses to contractile agonists, as seen in airway hyperresponsiveness. PMID- 1447095 TI - In vivo and in vitro correlation of trachealis muscle contraction in dogs. AB - Maximal trachealis muscle shortening in vivo was compared with that in vitro in seven anesthetized dogs. In addition, the effect of graded elastic loads on the muscle was evaluated in vitro. In vivo trachealis muscle shortening, as measured using sonomicrometry, revealed maximal active shortening to be 28.8 +/- 11.7% (SD) of initial length. Trachealis muscle preparations from the same animals were studied in vitro to evaluate isometric force generation, isotonic shortening, and the effect of applying linear elastic loads to the trachealis muscle during contraction from optimal length. Maximal isotonic shortening was 66.8 +/- 8.4% of optimal length in vitro. Increasing elastic loads decreased active shortening and velocity of shortening in vitro in a hyperbolic manner. The elastic load required to decrease in vitro shortening to the extent of the shortening observed in vivo was similar to the estimated load provided by the tracheal cartilage. We conclude that decreased active shortening in vivo is primarily due to the elastic afterload provided by cartilage. PMID- 1447096 TI - Immune responses and increased training of the elite athlete. AB - Ten elite male runners (age, 29.8 +/- 1.7 yr; maximum oxygen consumption, 65.3 +/ 4.9 ml.kg-1.min-1; 10-km times, 31 min 43 s +/- 1 min 46 s) deliberately increased training schedules by an average of 38% for 3 wk. Resting heart rate and maximal oxygen intake were unchanged, but the heart rate response to acute exercise was decreased. Following heavy training, blood samples taken at rest showed trends to a decreased helper/suppressor cell ratio, an increased phytohemagglutinin (PHA)- and concanavalin (ConA)-stimulated lymphocyte proliferation, and a decreased production of immunoglobulins IgG and IgM. Whereas PHA-stimulated lymphocyte proliferation was initially unchanged by acute exercise, after 3 wk of heavy training the same acute exercise caused an 18% suppression of proliferation. Acute exercise following heavy training did not alter pokeweed-stimulated IgG or IgM synthesis. There was no correlation between changes in lymphocyte subpopulations, helper/suppressor ratios, and mitogen induced cellular proliferation. The immune system of endurance-trained athletes at rest seemed to tolerate the stress of heavy training, but superimposition of a bout of acute exercise on the chronic stress of heavy training resulted in immunosuppression, which was transient and most likely not of clinical significance. PMID- 1447097 TI - Development of mucociliary transport in the postnatal ferret trachea. AB - Little is known of the developmental aspects of mucociliary transport. Previous studies have documented that newborn ferret trachea has very few ciliated cells but numerous immature secretory cells in the epithelium and only rudimentary submucosal glands. Rapid and complete maturation occurs in the first postnatal month. This study examines mucociliary transport during this period of rapid maturation. We made direct observations of particle movement across the epithelium of ferret tracheas. No mucus transport could be demonstrated on the first day of life. Transport was discernible, although sporadic and slow, by 7 days and reached adult levels (10.7 +/- 3.7 mm/min) by 28 postnatal days. The emergence of transport capability correlated well with previously described developmental changes in ciliation, mucus secretion, and ion permeability and transport. Threshold mucus transport occurred at 1 wk of age when 20-25% of the surface cells are ciliated. The neonatal ferret appears to be a useful model for assessing integrated epithelial structure-function relationships that are important not only during early development but also during repair after airway injury involving deciliation. PMID- 1447098 TI - Rat cardiovascular responses to whole body suspension: head-down and non-head down tilt. AB - The rat whole body suspension technique mimics responses seen during exposure to microgravity and was evaluated as a model for cardiovascular responses with two series of experiments. In one series, changes were monitored in chronically catheterized rats during 7 days of head-down tilt (HDT) or non-head-down tilt (N HDT) and after several hours of recovery. Elevations of mean arterial (MAP), systolic, and diastolic pressures of approximately 20% (P < 0.05) in HDT rats began as early as day 1 and were maintained for the duration of suspension. Pulse pressures were relatively unaffected, but heart rates were elevated approximately 10%. During postsuspension (2-7 h), most cardiovascular parameters returned to presuspension levels. N-HDT rats exhibited elevations chiefly on days 3 and 7. In the second series, blood pressure was monitored in 1- and 3-day HDT and N-HDT rats to evaluate responses to rapid head-up tilt. MAP, systolic and diastolic pressures, and HR were elevated (P < 0.05) in HDT and N-HDT rats during head-up tilt after 1 day of suspension, while pulse pressures remained unchanged. HDT rats exhibited elevated pretilt MAP and failed to respond to rapid head-up tilt with further increase of MAP on day 3, indicating some degree of deconditioning. The whole body suspended rat may be useful as a model to better understand responses of rats exposed to microgravity. PMID- 1447099 TI - Acute heat stress protects rats against endotoxin shock. AB - The purpose of this study was to determine 1) whether prior (24-h) heat stress could render rats cross-resistant to the lethal activity of bacterial lipopolysaccharide (LPS) and 2) whether this acquired state of resistance is associated with endotoxemia during the heat stress event. Four groups (n = 7/group) of rats were examined: 1) saline treated, 2) LPS treated, 3) heat stressed and saline treated, and 4) heat stressed and LPS treated. Saline or LPS (Escherichia coli, serotype 0111:B4, 20 mg/kg body wt) was given intravenously 24 h after exposure to heat (ambient temperature 47-50 degrees C, relative humidity 30%) for heat-stressed rats and at the same time of day for nonheated rats; survival was monitored for 48 h. Thermal responses were similar (P > 0.05); values for maximum core temperature (Tc) and time above Tc of 40 degrees C were 42.7 +/- 0.1 and 42.6 +/- 0.1 degrees C (SE) and 44.0 +/- 2.1 and 47.9 +/- 3.7 (SE) min for the heat-stressed saline-treated and heat-stressed LPS-treated rats, respectively. Administration of LPS to nonheated rats resulted in 71.4% (5 of 7 rats) lethality. In contrast, all (7 of 7) rats subjected to a single nonlethal heat stress event 24 h before LPS treatment survived (P < 0.05). Endotoxin was not detected in arterial plasma immediately after heat stress in rats (n = 6) exposed to a Tc of 42.9 +/- 0.1 degrees C. These findings demonstrate that acute heat stress can protect rats from the lethal activity of LPS. PMID- 1447100 TI - Muscle sympathetic nerve responses to static leg exercise. AB - Previous studies of muscle sympathetic nerve activity (MSNA) during static exercise have employed predominantly the arms. These studies have revealed striking increases in arm and leg MSNA during static handgrip (SHG) and postexercise circulatory arrest (PECA). The purpose of this study was to examine MSNA during static leg exercise (SLE) at intensities and duration commonly used during SHG followed by PECA. During 2 min of SLE (static knee extension) at 10% of maximal voluntary contraction (MVC; n = 18) in the sitting position, mean arterial pressure and heart rate increased significantly. Surprisingly, MSNA in the contralateral leg did not increase above control levels during SLE but rather decreased (23 +/- 5%; P < 0.05) during the 1st min of SLE at 10% MVC. We compared MSNA responses to SHG and SLE (n = 8) at 30% MVC. SHG and SLE elicited comparable increases (P < 0.05) in arterial pressure and heart rate, but SHG elicited significant increases in MSNA, whereas SLE did not. During PECA after SHG and SLE, mean arterial pressure remained significantly above control. However, MSNA was unchanged during PECA after SLE but was significantly greater than control during PECA after SHG. Because previous studies have indicated differences in MSNA responses to the arm and leg, we measured arm and leg MSNA simultaneously in six subjects during SLE at 20% MVC and PECA. During SLE and PECA, MSNA in the contralateral arm and leg did not differ significantly from each other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447101 TI - A model of ventilatory instability induced in the unrestrained rat. AB - A classic conditioning paradigm was used to examine the hypothesis that perturbations during sleep in the neonate rat can have a lasting impact on breathing. During the first 4 wk of life, stimuli were presented to rats during behaviorally defined sleep. In a conditioned hypoxic (CH) group, brief periods of hypoxic gas were used as the unconditioned stimulus. Tactile and auditory stimuli were used as the conditioned stimuli. In a conditioned control (CC) group, air was used as the unconditioned stimulus. A third group of unconditioned control (UC) rats was not exposed to the conditioning paradigm. Animals were provided routine care for 3.5 mo; ventilation was then assessed using plethysmography. Conditioning during neonatal life produced increased ventilatory irregularities and apnea during behaviorally defined sleep in adult rats. Both CH and CC rats showed a significantly greater number of apneic events compared with UC rats. Over a 2-h sleep period, CH rats exhibited a total of 105.1 +/- 9.4 (SE) apneic events, CC rats 69.4 +/- 4.2 events, and UC rats 42.1 +/- 3.1 events [F(2,18) = 25.568; P < 0.0001]. These findings suggest that experiences in the first few weeks of life will alter ventilatory patterning in the adult animal. PMID- 1447102 TI - Distribution of systemic blood flow in lambs with an aortopulmonary shunt during strenuous exercise. AB - We studied regional blood flows with radioactive-labeled microspheres in 12 7-wk old lambs with an aortopulmonary left-to-right shunt [59 +/- 3% (SE) of left ventricular (LV) output] and in 11 control lambs, at rest and during exercise at 80% of predetermined peak O2 consumption. At rest, systemic blood flow was similar in the two groups. Blood flow to the heart and diaphragm was substantially higher in the shunt than in the control lambs. Blood flow to the other organs was not significantly different between the two groups. During exercise, systemic blood flow increased substantially but less in shunt (81%) than in control lambs (134%). Blood flow to the heart and diaphragm increased, that to the heart still being higher in shunt than in control lambs. Blood flow to the brain did not change, whereas that to the kidneys and splanchnic organs decreased to the same extent (25%) in shunt and control lambs. Intrahepatic and intrarenal blood flow redistribution in the shunt lambs persisted during exercise. In conclusion, myocardial blood flow is not increased at the expense of one particular organ, nor is it associated with an essential change in exercise induced redistribution in shunt lambs. PMID- 1447103 TI - Ventilation is stimulated by small reductions in arterial pressure in the awake dog. AB - Changes in arterial pressure commonly accompany respiratory adaptations. The purpose of this study was to determine, in awake dogs (n = 6), the degree to which small acute decreases in arterial pressure affect ventilation and acid-base balance. Mean arterial pressure (MAP) was reduced by 6 +/- 2, 10 +/- 3, and 16 +/ 2% by intravenous infusion of sodium nitroprusside for sequential 20-min periods. In another experiment, the ventilatory response to hypercapnia was determined during MAP reduction of 16 +/- 3%. Step reductions in MAP were accompanied by increases in minute ventilation (maximum increase 152 +/- 75%) and step reductions in arterial PCO2 (PaCO2; maximum reduction -4.8 +/- 0.8 Torr). Although eupneic PaCO2 threshold was lowered during MAP reduction, ventilatory sensitivity to CO2 remained unchanged. Despite the lowered PaCO2, arterial [H+] remained constant (acid-base balance was maintained) as a result of a concurrent decrease in strong ion difference. Plasma renin activity increased during MAP reduction (93 +/- 39%) and may have contributed to the increase in minute ventilation, inasmuch as angiotensin II can stimulate respiration by a central mechanism. Evidence is provided that nitroprusside is unlikely to be a primary factor in these hypotensive responses. We conclude that relatively modest decreases in MAP have a consistent stimulatory effect on respiratory control. Therefore it is important to take into account effects of small changes in MAP when interpreting mechanisms for respiratory responses in awake animals. PMID- 1447104 TI - A respiratory sensory reflex in response to CO2 inhibits breathing in preterm infants. AB - Traditionally, the increase in ventilation occurring after approximately 4 s of CO2 inhalation in preterm infants has been attributed to an action at the peripheral chemoreceptors. However, on a few occasions, we have observed a short apnea (2-3 s) in response to 3-5% CO2 in these infants. To test the hypothesis that this apnea reflects a respiratory sensory reflex to CO2, we gave nine preterm infants [birth wt 1.5 +/- 0.1 (SE) kg, gestational age 31 +/- 1 wk] 7-8% CO2 while they breathed 21% O2. To study the dose-response relationship, we also gave 2, 4, 6, and 8% CO2 to another group of seven preterm infants (birth wt 1.5 +/- 0.1 kg, gestational age 31 +/- 1 wk). In the first group of infants, minute ventilation during 21% O2 breathing (0.232 +/- 0.022 l.min-1.kg-1) decreased after CO2 administration (0.140 +/- 0.022, P < 0.01) and increased with CO2 removal (0.380 +/- 0.054, P < 0.05). This decrease in ventilation was related to an apnea (12 +/- 2.6 s) occurring 7.7 +/- 0.8 s after the beginning of CO2 inhalation. There was no significant change in tidal volume. In the second group of infants, minute ventilation increased during administration of 2, 4, and 6% CO2 but decreased during 8% CO2 because of the presence of an apnea. These findings suggest that inhalation of a high concentration of CO2 (> 6%) inhibits breathing through a respiratory sensory reflex, as described in adult cats (H. A. Boushey and P. S. Richardson. J. Physiol. Lond. 228: 181-191, 1973).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447105 TI - Hormonal responses to exercise during moderate cold exposure in young vs. middle age subjects. AB - The influence of moderate cold exposure on the hormonal responses of atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, and plasma renin activity (PRA) after exhaustive exercise was studied in 9 young and 10 middle-aged subjects. Exercise tests were randomly performed in temperate (30 degrees C) and cold (10 degrees C) environments. Heart rate, oxygen consumption, and peripheral arterial blood pressure were measured at regular intervals. Blood samples were collected before and immediately after exercise at 30 or 10 degrees C. Plasma sodium and potassium concentrations as well as hemoglobin and hematocrit were measured, and the change in plasma volume was calculated. At rest and during exercise, oxygen consumption was similar during exposure to both temperate and cold temperatures. During submaximal exercise intensities, the rise in heart rate was blunted while the increase in systolic blood pressure was significantly greater at 10 than at 30 degrees C. The increases in plasma sodium and potassium concentrations after exhaustion were similar between environments, as was the decrease in plasma volume. In both groups, all plasma hormones were significantly elevated postexercise, with the AVP response similar at 10 and 30 degrees C. However, the norepinephrine and ANF responses were significantly greater while the PRA response was significantly reduced at 10 degrees C. In the middle-aged subjects the epinephrine response to exercise was higher at 10 than at 30 degrees C. The greater ANF and reduced PRA responses to exercise in the cold may have resulted from central hemodynamic changes caused by cold-induced cutaneous vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447106 TI - Cardiac cycle length variability in ponies at rest and during exercise. AB - We evaluated cardiac cycle length variability in ponies at rest and during strenuous exercise with and without premedication with atropine. In the absence of premedication, cardiac cycle length at rest was 1,112 +/- 53 ms, the individual cardiac cycle length standard deviation (SDCL) was 75 +/- 23 ms, and the individual cycle length coefficient of variation (CVCL) was 6.32 +/- 1.62. Exercise significantly decreased (P < 0.05) all three indexes (290 +/- 9 ms, 5 +/ 1 ms, and 1.65 +/- 0.20, respectively). Atropine premedication significantly reduced resting cardiac cycle length (685 +/- 46 ms), SDCL (10 +/- 2 ms), and CVCL (1.45 +/- 0.19) compared with nonpremedicated values. Cardiac cycle length was significantly decreased by exercise after atropine premedication, but no statistically significant changes occurred in SDCL or CVCL. Thus, although considerable cardiac cycle length variability exists in nonpremedicated ponies at rest, it is nearly completely abolished by strenuous exercise. The absence of significant differences between the indexes of variability during exercise without premedication, at rest after atropine, and during exercise after atropine indicates that cardiac cycle length variability in the pony is mediated primarily through activity of the parasympathetic system. PMID- 1447107 TI - Magnetic resonance imaging and electromyography as indexes of muscle function. AB - Electromyography (EMG) is commonly used to determine the electrical activity of skeletal muscle during contraction. To date, independent verification of the relationship between muscle use and EMG has not been provided. It has recently been shown that relaxation- (e.g., T2) weighted magnetic resonance images (MRI) of skeletal muscle demonstrate exercise-induced contrast enhancement that is graded with exercise intensity. This study was conducted to test the hypothesis that exercise-induced magnetic resonance (MR) contrast shifts would relate to EMG amplitude if both measures reflect muscle use during exercise. Both MRI and EMG data were collected for separate eccentric (ECC) and concentric (CON) exercise of increasing intensity to take advantage of the fact that the rate of increase and amplitude of EMG activity are markedly greater for CON muscle actions. Seven subjects 30 +/- 2 (SE) yr old performed five sets of 10 CON or ECC arm curls with each of four resistances representing 40, 60, 80, and 100% of their 10 repetition maximum for CON curls. There was 1.5 min between sets and 30 min between bouts (5 sets of 10 actions at each relative resistance). Multiple echo, transaxial T2 weighted MR images (1.5 T, TR/TE 2,000/30) were collected from a 7-cm region in the middle of the arm before exercise and immediately after each bout. Surface EMG signals were collected from both heads of the biceps brachii and the long head of the triceps brachii muscles. CON and ECC actions resulted in increased integrated EMG (IEMG) and T2 values that were strongly related (r = 0.99, P < 0.05) with relative resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447108 TI - Dehydrogenase conversion to oxidase and lipid peroxidation in brain after carbon monoxide poisoning. AB - The conversion of xanthine dehydrogenase to xanthine oxidase and lipid peroxidation were measured in brain from carbon monoxide- (CO) poisoned rats. Sulfhydryl-irreversible xanthine oxidase increased from a control level of 15% to a peak of 36% over the 90 min after CO poisoning, while the conjugated diene level doubled. Reversible xanthine oxidase was 3-6% of the total enzyme activity over this span of time but increased to 31% between 90 and 120 min after poisoning. Overall, reversible and irreversible xanthine oxidase represented 66% of total enzyme activity at 120 min after poisoning. Rats depleted of this enzyme by a tungsten diet and those treated with allopurinol before CO poisoning to inhibit enzyme activity exhibited no lipid peroxidation. Treatment immediately after poisoning with superoxide dismutase or deferoxamine inhibited lipid peroxidation but had no effect on irreversible oxidase formation. Biochemical changes only occurred after removal from CO, and changes could be delayed for hours by continuous exposure to 1,000 ppm CO. These results are consistent with the view that CO-mediated brain injury is a type of postischemic reperfusion phenomenon and indicate that xanthine oxidase-derived reactive oxygen species are responsible for lipid peroxidation. PMID- 1447109 TI - Factors affecting blood pressure during heavy weight lifting and static contractions. AB - Brachial arterial pressure was directly recorded in 31 healthy male volunteers through protocols examining the effects of the Valsalva maneuver, muscle size and strength, contraction force, contraction type (concentric, isometric, eccentric), changes in joint angle, and muscle fatigue on the blood pressure response to resistance exercise. Weight lifting at the same relative intensity produced similar increases in blood pressure, regardless of individual differences in muscle size or strength. Concentric, isometric, or eccentric exercise at the same relative intensity caused similar increases despite differences in force production. In weight lifting, the greatest increase in blood pressure occurred at the joint angle corresponding to the weakest point in the strength curve and the least at the angle corresponding to the strongest point. Isometric contractions of the same relative intensity at different joint angles produced identical blood pressures despite differences in absolute force production. When subjects attempted to maintain a maximum isometric contraction for 45 s, the blood pressure increase remained the same despite a marked diminution in force. Thus the magnitude of the blood pressure response depends on the degree of effort or central command and not actual force production. A brief Valsalva maneuver, which exaggerates the increase in blood pressure, is unavoidable when desired force production exceeds approximately 80% maximum voluntary contraction. PMID- 1447110 TI - Respiratory transfer impedance and derived mechanical properties of conscious rats. AB - A setup is described for measuring the respiratory transfer impedance of conscious rats in the frequency range 16-208 Hz. The rats were placed in a restraining tube in which head and body were separated by means of a dough neck collar. The restraining tube was placed in a body chamber, allowing the application of pseudorandom noise pressure variations to the chest and abdomen. The flow at the airway opening was measured in a small chamber connected to the body chamber. The short-term reproducibility of the transfer impedance was tested by repeated measurements in nine Wistar rats. The mean coefficient of variation for the impedance did not exceed 10%. The impedance data were analyzed using different models of the respiratory system of which a three-coefficient resistance-inertance-compliance model provided the most reliable estimates of respiratory resistance (Rrs) and inertance (Irs). The model response, however, departed systematically from the measured impedance. A nine-coefficient model best described the data. Optimization of this model provided estimates of the respiratory tissue coefficients and upper and lower airway coefficients. Rrs with this model was 13.6 +/- 1.0 (SD) kPa.l-1.s, Irs was 14.5 +/- 1.3 Pa.l-1.s2, and tissue compliance (Cti) was 2.5 +/- 0.5 ml/kPa. The intraindividual coefficient of variation for Rrs and Irs was 11 and 18%, respectively. Because most of the resistance and inertance was located in the airways (85 and 81% of Rrs and Irs, respectively), the partitioning in tissue and upper and lower airway components was rather poor. Our values for Rrs and Irs of conscious rats were much lower and our values for Cti were higher than previously reported values for anesthetized rats. PMID- 1447111 TI - Comparison of upper and lower airway responses of two sensitized rat strains to inhaled antigen. AB - The purpose of the study was to investigate the relationships between upper airways responses and pulmonary responses of two strains of highly inbred rats to inhaled antigen. To do this we measured the upper and lower airways resistance for 60 min after challenge of Brown-Norway rats (BN; n = 13) and an inbred rat strain (MF; n = 11), derived from Sprague-Dawley, with aerosolized ovalbumin (OA). Rats were actively sensitized with OA (1 mg sc) using Bordetella pertussis as an adjuvant. Two weeks later the animals were anesthetized and challenged. Tracheal pressure, esophageal pressure, and airflow were measured, from which total pulmonary resistance was partitioned into upper airway and lower pulmonary resistance (RL). The peak upper airway response to inhaled OA was similar in BN (1.89 +/- 0.66 cmH2O.ml-1.s; n = 7) and MF (2.85 +/- 0.68 cmH2O.ml-1.s; n = 6). The lower airway response to OA challenge was substantially greater in BN, and RL changed from 0.07 +/- 0.01 to 0.34 +/- 0.13 (n = 6; P < 0.05). The MF did not have any significant increase in RL after challenge; the baseline RL was 0.12 +/- 0.02 and only reached a peak value of 0.15 +/- 0.05 (n = 5; P = NS). Lower airway responsiveness of BN (n = 10) to serotonin, an important mediator early allergic airway responses, was similar to MF (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447112 TI - Diaphragmatic microcirculation during halothane and isoflurane exposure in pentobarbital-anesthetized rats. AB - We investigated the effects of halothane and isoflurane on diaphragmatic microcirculation in pentobarbital-anesthetized rats by in vivo video microscopy. After a baseline period, rats were randomly allocated into three groups according to administration of 0.5, 0.75, and 1 minimal alveolar concentration (MAC) of either halothane (group Hal, n = 16), isoflurane (group Iso, n = 14), or no halogenated agent (group C, n = 20) in three succeeding steps of 15 min. Mean arterial blood pressure (MAP), arteriolar diameters, and functional capillary density were analyzed in the last 3 min of each step. MAP remained unchanged in group C but decreased in a dose-dependent manner in both halogenated receiving groups. MAP was significantly lower in rats breathing Hal compared with those breathing Iso. Arterioles were classified in second (A2, n = 39), third (A3, n = 24), and fourth (A4, n = 30) order according to their relative location in the network. No changes in A2 and A3 diameters were noted in either group. A4 diameters remained unchanged in groups C and Iso, whereas a significant reduction was found in group Hal at 0.75 and 1 MAC exposure (P < 0.05 compared with baseline and with groups C and Iso, respectively). During Iso exposure, functional capillary density was not significantly different when compared with baseline and group C, whereas in group Hal it decreased significantly at 0.5, 0.75, and 1 MAC, amounting to 61.1 +/- 9, 30.7 +/- 10.3, and 22.8 +/- 6.3%, respectively, of baseline (P < 0.01 vs. baseline and P < 0.05 vs. groups Iso and C for 0.75 and 1 MAC).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447113 TI - Chest wall distortion and discharge of pulmonary slowly adapting receptors. AB - We assessed the effects of chest wall distortion, changes in lung volume, and abolition of airway smooth muscle tone on the discharge patterns of 92 pulmonary slowly adapting receptors (SAR) in decerebrate, spontaneously breathing cats. Distortion resulted from their inspiratory efforts against an occluded airway at functional residual capacity and at increased end-expiratory lung volumes. Approximately 40% of SAR increased discharge frequencies during occlusions. Modulation of SAR discharge during occlusions persisted after administration of atropine to eliminate airway smooth muscle tone. Phasic modulation of SAR discharge was eliminated during no-inflation tests after paralyzing the cats and ventilating them on a cycle-triggered pump. We conclude 1) parasympathetic modulation of airway smooth muscle tone makes no obvious contribution to SAR discharge in spontaneously breathing cats; 2) the no-inflation test (withholding of lung inflation during neural inspiration) in paralyzed and ventilated cats is a valid test for the presence of projections from SAR to medullary respiratory neurons; and 3) in the absence of tidal volume changes, distortion stimulates some SAR. Sensory feedback from receptors in the lung, not just those in the chest wall, may therefore provide information about abnormal chest wall configurations. PMID- 1447114 TI - Discharge patterns of phrenic motoneurons during fictive coughing and vomiting in decerebrate cats. AB - In decerebrate, paralyzed, and ventilated cats, we recorded the activity of 100 spontaneously active phrenic motor axons during the increased phrenic discharges characteristic of fictive vomiting (FV) and coughing (FC). During control respiratory cycles, approximately one-half the neurons were recruited in the first decile of inspiration; recruitment continued throughout inspiration. During FV, the duration of phrenic discharge was halved; 20 of 26 motoneurons studied were recruited in the first decile of the burst. During FC, recruitment times did not change compared with control, although the duration of the phrenic burst doubled. Discharge frequencies increased and recruitment order of phrenic motoneurons was virtually unaffected during FC and FV. Limited recruitment of previously inactive neurons in the filaments from which we recorded was found during FV and FC. During FV, 1 previously inactive motoneuron was recruited in 16 filaments containing 25 spontaneously active motor axons. During FC, 3 new motoneurons were recruited in addition to the 64 already active in 35 filaments. Recruitment during FV and FC was absent even when recording from filaments known, on the basis of antidromic activation, to contain inactive motor axons. During FV, 10 of 26 motoneurons began their discharges with doublets (interspike interval < 10 ms); doublets occurred in only 4 of 67 motoneurons during FC. Already active phrenic motoneurons contributed to the intense phrenic activity associated with both respiratory (coughing) and nonrespiratory (vomiting) behavior by increases in discharge frequency, earlier recruitment, and doublets; the contribution of previously quiescent motoneurons remains uncertain. PMID- 1447115 TI - Phosphocreatine hydrolysis by 31P-NMR at the onset of constant-load exercise in humans. AB - The kinetics of phosphocreatine (PC) breakdown in human plantar flexors at the onset of constant-load aerobic exercise was determined by high-resolution 31P nuclear magnetic resonance spectroscopy (NMRS). The half time of the process (t1/2PC) was obtained by fitting curves (n = 13) from five subjects at various aerobic work loads for which muscle pH was not different from that at rest. Steady-state PC concentration ([PC]) was not < 70% of the resting value and was linearly related to the work load (w) ([PC] = -3.01 +/- 0.08 w + 1 (r = 0.48, 2P < 0.1)). The average t1/2PC was 16.2 s and was independent of work load. Because the half time of the muscle PC kinetics reflects the half time of the O2 uptake (MO2) kinetics (t1/2MO2), the latter is equal to that found earlier in the isolated perfused dog gastrocnemius. Whereas in the dog the above t1/2MO2 compares well with the homologous half time of the O2 uptake at the alveolar level, in humans such equivalence is found only at extremely low work loads, when the transient contribution by anaerobic glycolysis is negligible. PMID- 1447116 TI - Effects of unilateral hyperinflation on the interpulmonary distribution of pleural pressure. AB - Motivated by single lung transplantation, we studied the mechanics of the chest wall during single lung inflations in recumbent dogs and baboons and determined how pleural pressure (Ppl) is coupled between the hemithoraces. In one set of experiments, the distribution of Ppl was inferred from known volumes and elastic properties of each lung. In a second set of experiments, costal pleural liquid pressure (Pplcos) was measured with rib capsules. Both methods revealed that the increase in Ppl over the ipsilateral or inflated lung (delta Ppli) is greater than that over the contralateral or noninflated lung (delta Pplc). Mean d(delta Pplc)/d(delta Ppli) and its 95% confidence interval was 0.7 +/- 0.1 in dogs and 0.5 +/- 0.1 in baboons. In a third set of experiments in three dogs and three baboons, we prevented sternal displacement and exposed the abdominal diaphragm to atmospheric pressure during unilateral lung inflation. These interventions had no significant effect on Ppl coupling between the hemithoraces. We conclude that lungs of unequal size and mechanical properties need not be exposed to the same surface pressure, because thoracic midline structures and the lungs themselves resist displacement and deformation. PMID- 1447117 TI - Longitudinal distribution of ozone absorption in the lung: quiet respiration in healthy subjects. AB - The objective of this research was to develop a bolus-response method for the noninvasive determination of O3 distribution in the human lung. A previously developed O3 analyzer and bolus generator were incorporated in a computer controlled inhalation system, and measurements of O3 absorption from inhaled 10 ml boluses with a peak O3 concentration of 4 ppm were carried out on nine previously unexposed healthy male subjects engaged in quiet oral breathing. The fraction of O3 absorbed during a single breath was measured over a range of airway penetrations from 20 to 200 ml, with inspiratory and expiratory flows fixed at a nominal value of 250 ml/s. The resulting data indicated that 50% of the inhaled O3 was absorbed at a penetration of 70 ml, which roughly corresponds to the upper airways, and essentially complete absorption occurred at a penetration of 180 ml, which roughly corresponds to the 16th airway generation, the beginning of the proximal alveolar region. This compares favorably with the results of direct-sampling methods, which indicated that 40.4% of continuously inhaled O3 is removed by the extrathoracic airways (Gerrity et al. J. Appl. Physiol. 65: 393-400, 1988). The computation of an absorption rate constant, Ka, revealed that the efficiency of O3 uptake increased with longitudinal position throughout most of the conducting airways but began to fall off at a penetration of 160 ml. PMID- 1447118 TI - A 31P-NMR study of tissue respiration in working dog muscle during reduced O2 delivery conditions. AB - To investigate the role of tissue oxygenation as one of the control factors regulating tissue respiration, 31P-nuclear magnetic resonance spectroscopy (31P NMR) was used to estimate muscle metabolites in isolated working muscle during varied tissue oxygenation conditions. O2 delivery (muscle blood flow x arterial O2 content) was varied to isolated in situ working dog gastrocnemius (n = 6) by decreases in arterial PO2 (hypoxemia; H) and by decreases in muscle blood flow (ischemia; I). O2 uptake (VO2) was measured at rest and during work at two or three stimulation intensities (isometric twitch contractions at 3, 5, and occasionally 7 Hz) during three separate conditions: normal O2 delivery (C) and reduced O2 delivery during H and I, with blood flow controlled by pump perfusion. Biochemical metabolites were measured during the last 2 min of each 3-min work period by use of 31P-NMR, and arterial and venous blood samples were drawn and muscle blood flow measured during the last 30 s of each work period. Muscle [ATP] did not fall below resting values at any work intensity, even during O2-limited highly fatiguing work, and was never different among the three conditions. Muscle O2 delivery and VO2 were significantly less (P < 0.05) at the highest work intensities for both I and H than for C but were not different between H and I. As VO2 increased with stimulation intensity, a larger change in any of the proposed regulators of tissue respiration (ADP, P(i), ATP/ADP.P(i), and phosphocreatine) was required during H and I than during C to elicit a given VO2, but requirements were similar for H and I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447119 TI - Ventilatory failure induced by tracheal banding in the hamster. AB - Previous animal models of hypercapnic ventilatory failure are limited in that the resistive load has only been applied acutely and often in anesthetized animals. We therefore developed a chronic animal model of hypercapnic ventilatory failure by increasing airway resistance via tracheal banding over several days. To test the efficacy of this model, we compared arterial blood gases, pulmonary function, and internal area of the trachea 6 days after the banding or sham procedure in 20 hamsters. Six days later, banded animals had an increased airway resistance as indicated by a 66% reduction in internal cross-sectional area of the trachea and a 6.5-fold increase in pulmonary resistance compared with control hamsters. The increased airway resistance resulted in a severe respiratory acidosis and hypoxemia in the awake banded hamsters. Banded hamsters were also hyperinflated. This animal model will be useful for investigating the various mechanisms that contribute to hypercapnic ventilatory failure and interventions that may promote recovery. PMID- 1447120 TI - Transvalvular left ventricular pressure measurement in the isolated working rat heart. AB - A method of continuously measuring left ventricular (LV) pressure in an isolated buffer-perfused working rat heart is described. Transvalvular placement of a micromanometer through the aorta is the unique feature of this procedure. Advantages include catheter stability and lack of myocardial trauma. Changes in cardiac function were quantified by exposing hearts to either isoproterenol (10( 9) M) or halothane (1.5% vol/vol). To examine if any obstruction to LV outflow was caused by the micromanometer, cardiac performance was assessed during pullback from the ventricle to the aorta. Complications such as aortic insufficiency and ventricular arrhythmias were also studied. The results indicate that the transvalvular placement of a micromanometer can provide continuous, high fidelity reproduction of LV pressure in this small-organ preparation. The presence of the micromanometer did not significantly alter cardiac performance, and proper catheter placement was achieved easily in a high percentage (> 90%) of cases. PMID- 1447121 TI - Neutrophil retention during a single transit through the pulmonary circulation. AB - Our laboratory has previously reported that 70-80% of polymorphonuclear cells (PMNs) are delayed with respect to erythrocytes (RBCs) in a single pass through the lungs of dogs, whereas only 5-15% of PMNs are delayed in a single pass through human lungs. Because these results were obtained using a direct blood sampling method in animals and an indirect gamma camera method in humans, the reported differences could be related to differences in measurement technique. The present study was designed to settle this question by comparing both techniques in a single species. The results show that the gamma camera technique previously used in humans underestimates the retention of PMNs with respect to RBCs during a single pass through the lung. They also show that this problem can be corrected by modifying the analysis of the data obtained using the gamma camera. We conclude that the pulmonary circulation retains PMNs with respect to RBCs to a comparable degree in animals and humans. PMID- 1447122 TI - IL-1 receptor antagonist release is regulated differently in human alveolar macrophages than in monocytes. AB - These studies compared the release of interleukin-1 receptor antagonist (IL-1 RA) from alveolar macrophages and peripheral blood monocytes. The cells were cultured in medium containing various amounts of heat-inactivated fetal calf serum (FCS), granulocyte-macrophage colony-stimulating factor (GM-CSF), lipopolysaccharide (LPS), and immunoglobulin G (IgG). In serum-free medium alone, IL-1 RA release was similar from macrophages and monocytes. Increasing FCS concentration caused a significant upregulation of IL-1 RA release in macrophages but not in monocytes. GM-CSF caused a small increase in both cell types. LPS caused downregulation of IL-1 RA release from monocytes but not from macrophages. IgG did not affect IL-1 RA release in either cell group. These studies demonstrate that regulation of IL 1 RA release is different in monocytes and macrophages. PMID- 1447123 TI - Evans blue (T-1824) and albumin clearances. PMID- 1447124 TI - Chromosomal insertion sites for phages and plasmids. PMID- 1447125 TI - Identification and characterization of the smbA gene, a suppressor of the mukB null mutant of Escherichia coli. AB - The mukB gene encodes a protein involved in chromosome partitioning in Escherichia coli. To study the function of this protein, we isolated from the temperature-sensitive mukB null mutant and characterized 56 suppressor mutants which could grow at 42 degrees C. Ten of the mutants also showed cold-sensitive growth at 22 degrees C. Using one of the cold-sensitive mutants as host, the wild type of the suppressor gene was cloned. The cloned suppressor gene complemented all of the 56 suppressor mutations. DNA sequencing revealed the presence of an open reading frame of 723 bp which could encode a protein of 25,953 Da. The gene product was indeed detected. The previously undiscovered gene, named smbA (suppressor of mukB), is located at 4 min on the E. coli chromosome, between the tsf and frr genes. The smbA gene is essential for cell proliferation in the range from 22 to 42 degrees C. Cells which lacked the SmbA protein ceased macromolecular synthesis. The smbA mutants are sensitive to a detergent, sodium dodecyl sulfate, and they show a novel morphological phenotype under nonpermissive conditions, suggesting a defect in specific membrane sites. PMID- 1447126 TI - Expression and regulation of the RepA protein of the RepFIB replicon from plasmid P307. AB - The control of RepFIB replication appears to rely on the interaction between an initiator protein (RepA) and two sets of DNA repeat elements located on either side of the repA gene. Limited N-terminal sequence information obtained from a RepA:beta-galactosidase fusion protein indicates that although the first residue of RepA is methionine, the initiation of translation of RepA occurs from a CTG codon rather than from the predicted GTG codon located further downstream. Overexpressed RepA in trans is capable of repressing a repA:lacZ fusion plasmid in which the expression of the fusion protein is under the control of the repA promoter. The repA promoter has been located functionally by testing a series of repA:lacZ fusion plasmids. Both in vivo genetic tests and in vitro DNA-binding studies indicate that repA autoregulation can be achieved by RepA binding to one or more repeat elements which overlap the repA promoter sequence. PMID- 1447127 TI - Bacterial metabolism of naphthalene: construction and use of recombinant bacteria to study ring cleavage of 1,2-dihydroxynaphthalene and subsequent reactions. AB - The reactions involved in the bacterial metabolism of naphthalene to salicylate have been reinvestigated by using recombinant bacteria carrying genes cloned from plasmid NAH7. When intact cells of Pseudomonas aeruginosa PAO1 carrying DNA fragments encoding the first three enzymes of the pathway were incubated with naphthalene, they formed products of the dioxygenase-catalyzed ring cleavage of 1,2-dihydroxynaphthalene. These products were separated by chromatography on Sephadex G-25 and were identified by 1H and 13C nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry as 2-hydroxychromene-2 carboxylate (HCCA) and trans-o-hydroxybenzylidenepyruvate (tHBPA). HCCA was detected as the first reaction product in these incubation mixtures by its characteristic UV spectrum, which slowly changed to a spectrum indicative of an equilibrium mixture of HCCA and tHBPA. Isomerization of either purified product occurred slowly and spontaneously to give an equilibrium mixture of essentially the same composition. tHBPA is also formed from HCCA by the action of an isomerase enzyme encoded by plasmid NAH7. The gene encoding this enzyme, nahD, was cloned on a 1.95-kb KpnI-BglII fragment. Extracts of Escherichia coli JM109 carrying this fragment catalyzed the rapid equilibration of HCCA and tHBPA. Metabolism of tHBPA to salicylaldehyde by hydration and aldol cleavage is catalyzed by a single enzyme encoded by a 1-kb MluI-StuI restriction fragment. A mechanism for the hydratase-aldolase-catalyzed reaction is proposed. The salicylaldehyde dehydrogenase gene, nahF, was cloned on a 2.75-kb BamHI fragment which also carries the naphthalene dihydrodiol dehydrogenase gene, nahB. On the basis of the identification of the enzymes encoded by various clones, the gene order for the nah operon was shown to be p, A, B, F, C, E, D. PMID- 1447128 TI - Rhizobium nodM and nodN genes are common nod genes: nodM encodes functions for efficiency of nod signal production and bacteroid maturation. AB - Earlier, we showed that Rhizobium meliloti nodM codes for glucosamine synthase and that nodM and nodN mutants produce strongly reduced root hair deformation activity and display delayed nodulation of Medicago sativa (Baev et al., Mol. Gen. Genet. 228:113-124, 1991). Here, we demonstrate that nodM and nodN genes from Rhizobium leguminosarum biovar viciae restore the root hair deformation activity of exudates of the corresponding R. meliloti mutant strains. Partial restoration of the nodulation phenotypes of these two strains was also observed. In nodulation assays, galactosamine and N-acetylglucosamine could substitute for glucosamine in the suppression of the R. meliloti nodM mutation, although N acetylglucosamine was less efficient. We observed that in nodules induced by nodM mutants, the bacteroids did not show complete development or were deteriorated, resulting in decreased nitrogen fixation and, consequently, lower dry weights of the plants. This mutant phenotype could also be suppressed by exogenously supplied glucosamine, N-acetylglucosamine, and galactosamine and to a lesser extent by glucosamine-6-phosphate, indicating that the nodM mutant bacteroids are limited for glucosamine. In addition, by using derivatives of the wild type and a nodM mutant in which the nod genes are expressed at a high constitutive level, it was shown that the nodM mutant produces significantly fewer Nod factors than the wild-type strain but that their chemical structures are unchanged. However, the relative amounts of analogs of the cognate Nod signals were elevated, and this may explain the observed host range effects of the nodM mutation. Our data indicate that both the nodM and nodN genes of the two species have common functions and confirm that NodM is a glucosamine synthase with the biochemical role of providing sufficient amounts of the sugar moiety for the synthesis of the glucosamine oligosaccharide signal molecules. PMID- 1447129 TI - Scattering of the rRNA genes on the physical map of the circular chromosome of Leptospira interrogans serovar icterohaemorrhagiae. AB - Leptospira interrogans is a pathogenic bacterium with a low G+C content (34 to 39%). The restriction enzymes NotI, AscI, and SrfI cut the chromosome of L. interrogans serovar icterohaemorrhagiae into 13, 3, and 5 fragments separable by one- and two-dimensional pulsed-field gel electrophoresis (PFGE). The genome is composed of a circular 4.6-Mbp chromosome and a 0.35-Mbp extrachromosomal element. A physical map of the chromosome was constructed for NotI, AscI, and SrfI by using single and double digests, or partial NotI digests obtained at random or by cross-protection of NotI sites by FnuDII methylase, and linking clones. rRNA genes were found to be widely scattered on the chromosome. PMID- 1447130 TI - Possible role of Escherichia coli penicillin-binding protein 6 in stabilization of stationary-phase peptidoglycan. AB - Plasmids for high-level expression of penicillin-binding protein 6 (PBP6) were constructed, giving rise to overproduction of PBP6 under the control of the lambda pR promoter in either the periplasmic or the cytoplasmic space. In contrast to penicillin-binding protein 5 (PBP5), the presence of high amounts of PBP6 in the periplasm as well as in the cytoplasm did not result in growth as spherical cells or in lysis. Deletion of the C-terminal membrane anchor of PBP6 resulted in a soluble form of the protein (PBP6s350). Electron micrographs of thin sections of cells overexpressing both native membrane-bound and soluble PBP6 in the periplasm revealed a polar retraction of the cytoplasmic membrane. Cytoplasmic overexpression of native PBP6 gave rise to the formation of membrane vesicles, whereas the soluble PBP6 formed inclusion bodies in the cytoplasm. Both the membrane-bound and the soluble forms of PBP6 were purified to homogeneity by using the immobilized dye Procion rubine MX-B. Purified preparations of PBP6 and PBP6s350 formed a 14[C]penicillin-protein complex at a 1:1 stoichiometry. The half-lives of the complexes were 8.5 and 6 min, respectively. In contrast to PBP5, no DD-carboxypeptidase activity could be detected for PBP6 by using bisacetyl-L-Lys-D-Ala-D-Ala and several other substrates. These findings led us to conclude that PBP6 has a biological function clearly distinct from that of PBP5 and to suggest a role for PBP6 in the stabilization of the peptidoglycan during stationary phase. PMID- 1447132 TI - Resolution and some properties of enzymes involved in enantioselective transformation of 1,3-dichloro-2-propanol to (R)-3-chloro-1,2-propanediol by Corynebacterium sp. strain N-1074. AB - During the course of the transformation of 1,3-dichloro-2-propanol (DCP) into (R) 3-chloro-1,2-propanediol [(R)-MCP] with the cell extract of Corynebacterium sp. strain N-1074, epichlorohydrin (ECH) was transiently formed. The cell extract was fractionated into two DCP-dechlorinating activities (fractions Ia and Ib) and two ECH-hydrolyzing activities (fractions IIa and IIb) by TSKgel DEAE-5PW column chromatography. Fractions Ia and Ib catalyzed the interconversion of DCP to ECH, and fractions IIa and IIb catalyzed the transformation of ECH into MCP. Fractions Ia and IIa showed only low enantioselectivity for each reaction, whereas fractions Ib and IIb exhibited considerable enantioselectivity, yielding R-rich ECH and MCP, respectively. Enzymes Ia and Ib were isolated from fractions Ia and Ib, respectively. Enzyme Ia had a molecular mass of about 108 kDa and consisted of four subunits identical in molecular mass (about 28 kDa). Enzyme Ib was a protein of 115 kDa, composed of two different polypeptides (about 35 and 32 kDa). The specific activity of enzyme Ib for DCP was about 30-fold higher than that of enzyme Ia. Both enzymes catalyzed the transformation of several halohydrins into the corresponding epoxides with liberation of halides and its reverse reaction. Their substrate specificities and immunological properties differed from each other. Enzyme Ia seemed to be halohydrin hydrogen-halide-lyase which was already purified from Escherichia coli carrying a gene from Corynebacterium sp. strain N 1074. PMID- 1447131 TI - Identification, isolation, and structural studies of the outer membrane lipopolysaccharide of Caulobacter crescentus. AB - The lipopolysaccharide (LPS) of the outer membrane of Caulobacter crescentus was purified and analyzed. Two distinct strains of the species, NA 1000 and CB2A, were examined; despite differences in other membrane-related polysaccharides, the two gave similar LPS composition profiles. The LPS was the equivalent of the rough LPS described for other bacteria in that it lacked the ladder of polysaccharide-containing species that results from addition of variable amounts of a repeated sequence of sugars, as detected by gel electrophoresis in smooth LPS strains. The purified LPS contained two definable regions: (i) an oligosaccharide region, consisting of an inner core of three residues of 2-keto-3 deoxyoctonate, two residues of alpha-L-glycero-D-mannoheptose, and one alpha-D glycero-D-mannoheptose unit and an outer core region containing one residue each of alpha-D-mannose, alpha-D-galactose, and alpha-D-glucose, with the glucose likely phosphorylated and (ii) a region equivalent to the lipid A region of the archetype, consisting primarily of an esterified fatty acid, 3-OH-dodecanoate. The lipid A-like region was resistant to conclusive analysis; in particular, although a variety of analytical methods were used, no amino sugars were detected, as is found in the lipid A of the LPS of most bacteria. PMID- 1447133 TI - Expression of the repA1 gene of IncFII plasmid NR1 is translationally coupled to expression of an overlapping leader peptide. AB - Examination of a group of mutants of plasmid NR1 that had lost the expression of IncFII plasmid incompatibility (Inc-) revealed a group that had also lost replication proficiency (Rep-). These mutants were obtained from plasmids in which the NR1 replication control region was present in a cointegrate with plasmid pBR322. Whereas the wild-type parental cointegrate plasmid was capable of replicating in a polA host owing to the PolA independence of NR1 replication, the mutants were not able to transform a polA host. Losses of both expression of IncFII plasmid incompatibility and replication proficiency were found to result from the same single base-pair substitution in four independently isolated Inc- Rep- mutants. The mutation inactivates promoter PE for the transcription of RNA E, a trans-acting repressor of translation of the essential RepA1 replication initiation protein of NR1. Although the loss of RNA-E synthesis had been expected to increase the expression of repA1, the efficiency of translation of repA1 mRNA from these mutants was at least 100-fold lower than that from the wild type, as revealed by repA1-lacZ translational fusions. The PE mutation introduced a stop codon into a 24-amino-acid reading frame that precedes the repA1 gene and terminates just 2 bp downstream from the repA1 start codon. This putative leader peptide was also expressed in a lacZ translational fusion, and its expression was reduced by a factor of 10(4) by the PE mutation. The expression of the leader peptide and the expression of repA1 were regulated by RNA-E. These results suggest that the expression of repA1 is coupled to the translation of the leader peptide and that the repression of repA1 translation by RNA-E may occur via inhibition of the translation of the leader peptide. PMID- 1447134 TI - Carbon and energy metabolism of atp mutants of Escherichia coli. AB - The membrane-bound H(+)-ATPase plays a key role in free-energy transduction of biological systems. We report how the carbon and energy metabolism of Escherichia coli changes in response to deletion of the atp operon that encodes this enzyme. Compared with the isogenic wild-type strain, the growth rate and growth yield were decreased less than expected for a shift from oxidative phosphorylation to glycolysis alone as a source of ATP. Moreover, the respiration rate of a atp deletion strain was increased by 40% compared with the wild-type strain. This result is surprising, since the atp deletion strain is not able to utilize the resulting proton motive force for ATP synthesis. Indeed, the ratio of ATP concentration to ADP concentration was decreased from 19 in the wild type to 7 in the atp mutant, and the membrane potential of the atp deletion strain was increased by 20%, confirming that the respiration rate was not controlled by the magnitude of the opposing membrane potential. The level of type b cytochromes in the mutant cells was 80% higher than the level in the wild-type cells, suggesting that the increased respiration was caused by an increase in the expression of the respiratory genes. The atp deletion strain produced twice as much by-product (acetate) and exhibited increased flow through the tricarboxylic acid cycle and the glycolytic pathway. These three changes all lead to an increase in substrate level phosphorylation; the first two changes also lead to increased production of reducing equivalents. We interpret these data as indicating that E. coli makes use of its ability to respire even if it cannot directly couple this ability to ATP synthesis; by respiring away excess reducing equivalents E. coli enhances substrate level ATP synthesis. PMID- 1447135 TI - In vitro transcription from the Escherichia coli ilvIH promoter. AB - Lrp (leucine-responsive regulatory protein) activates the expression of the Escherichia coli ilvIH operon in vivo and mediates the repression of the operon by exogenous leucine. In previous studies, operon expression in vivo was measured with transcriptional fusions of lacZ to the ilvIH promoter. Here, ilvIH mRNA was measured directly by primer extension. The steady-state level of ilvIH mRNA was 11-fold higher in a wild-type parent strain than in a derivative lacking Lrp. A two-step procedure was developed for measuring ilvIH mRNA synthesized in vitro. RNA was synthesized with plasmid templates and purified RNA polymerase, and then ilvIH mRNA was measured by primer extension. In vitro, mRNA synthesis was initiated at two sites, one corresponding to the in vivo site (promoter P1) and the other corresponding to a site about 60 bp further upstream (promoter P2). Purified Lrp stimulated transcription two- to fivefold from promoter P1, whereas it decreased transcription more than fivefold from promoter P2. Transcription from promoter P1 was stimulated by Lrp with templates containing the wild-type ilvIH promoter but not with templates containing mutations in an Lrp binding site. Furthermore, under at least some conditions, leucine reversed the stimulatory effect of Lrp. Taken together with the results of mutational analyses, these results establish that Lrp acts directly to stimulate transcription from the ilvIH promoter. Furthermore, they suggest that the ilvIH promoter is recognized by a sigma 70 RNA polymerase. PMID- 1447136 TI - N5-methyl-tetrahydromethanopterin:coenzyme M methyltransferase of Methanosarcina strain Go1 is an Na(+)-translocating membrane protein. AB - To determine the cellular localization of components of the methyltransferase system, we separated cell extracts of Methanosarcina strain Go1 into cytoplasmic and inverted-vesicle fractions. Measurements demonstrated that 83% of the methylene-tetrahydromethanopterin reductase activity resided in the cytoplasm whereas 88% of the methyl-tetrahydromethanopterin:coenzyme M methyltransferase (methyltransferase) was associated with the vesicles. The activity of the methyltransferase was stimulated 4.6-fold by ATP and 10-fold by ATP plus a reducing agent [e.g., Ti(III)]. In addition, methyltransferase activity depended on the presence of Na+ (apparent Km = 0.7 mM) and Na+ was pumped into the lumen of the vesicles in the course of methyl transfer from methyl tetrahydromethanopterin not only to coenzyme M but also to hydroxycobalamin. Both methyl transfer reactions were inhibited by 1-iodopropane and reconstituted by illumination. A model for the methyl transfer reactions is presented. PMID- 1447137 TI - Characterization of a high-affinity iron transport system in Acinetobacter baumannii. AB - Analysis of a clinical isolate of Acinetobacter baumannii showed that this bacterium was able to grow under iron-limiting conditions, using chemically defined growth media containing different iron chelators such as human transferrin, ethylenediaminedi-(o-hydroxyphenyl)acetic acid, nitrilotriacetic acid, and 2,2'-bipyridyl. This iron uptake-proficient phenotype was due to the synthesis and secretion of a catechol-type siderophore compound. Utilization bioassays using the Salmonella typhimurium iron uptake mutants enb-1 and enb-7 proved that this siderophore is different from enterobactin. This catechol siderophore was partially purified from culture supernatants by adsorption chromatography using an XAD-7 resin. The purified component exhibited a chromatographic behavior and a UV-visible light absorption spectrum different from those of 2,3-dihydroxybenzoic acid and other bacterial catechol siderophores. Furthermore, the siderophore activity of this extracellular catechol was confirmed by its ability to stimulate energy-dependent uptake of 55Fe(III) as well as to promote the growth of A. baumannii bacterial cells under iron-deficient conditions imposed by 60 microM human transferrin. Polyacrylamide gel electrophoresis analysis showed the presence of iron-regulated proteins in both inner and outer membranes of this clinical isolate of A. baumannii. Some of these membrane proteins may be involved in the recognition and internalization of the iron-siderophore complexes. PMID- 1447138 TI - Alginate synthesis in Pseudomonas aeruginosa: environmental regulation of the algC promoter. AB - The exopolysaccharide alginate is a major virulence factor of Pseudomonas aeruginosa strains that infect the lungs of cystic fibrosis patients. The synthesis of alginate is almost uniquely associated with the pathogenicity of P. aeruginosa within the environment of the cystic fibrosis lung. The gene algC is one of the essential alginate biosynthetic genes and codes for the enzyme phosphomannomutase. In this report, we present data on the transcriptional regulation of algC expression. The activity of the algC promoter is modulated by the response regulator, AlgR1, a member of the two-component signal transduction protein family, which also regulates other alginate-specific promoters. In both mucoid (alginate-positive) and nonmucoid (alginate-negative) P. aeruginosa strains, transcriptional activation of algC increased with the osmolarity of the culture medium. This osmolarity-induced activation was found to be dependent on AlgR1. AlgR1 was found to interact directly with the algC promoter. Deletion mapping, in conjunction with mobility shift assays, showed that AlgR1 specifically bound with two regions of algC upstream DNA. A fragment spanning nucleotide positions -378 to -73 showed strong specific binding, while a fragment located between positions -73 and +187 interacted relatively weakly with AlgR1. Phosphorylation of the AlgR1 protein resulted in the stimulation of its in vitro ability to bind to the algC promoter region (a fragment spanning nucleotides -378 to -73). Transcription from the algC promoter, which has significant homology with the RNA polymerase sigma-54 (RpoN) recognition sequence, decreased in an rpoN mutant of P. aeruginosa. PMID- 1447139 TI - Evidence for ATP binding and double-stranded DNA binding by Escherichia coli RecF protein. AB - RecF protein is one of the important proteins involved in DNA recombination and repair. RecF protein has been shown to bind single-stranded DNA (ssDNA) in the absence of ATP (T. J. Griffin IV and R. D. Kolodner, J. Bacteriol. 172:6291-6299, 1990; M. V. V. S. Madiraju and A. J. Clark, Nucleic Acids Res. 19:6295-6300, 1991). In the present study, using 8-azido-ATP, a photo-affinity analog of ATP, we show that RecF protein binds ATP and that the binding is specific in the presence of DNA. 8-Azido-ATP photo-cross-linking is stimulated in the presence of DNA (both ssDNA and double-stranded DNA [dsDNA]), suggesting that DNA enhances the affinity of RecF protein for ATP. These data suggest that RecF protein possesses independent ATP- and DNA-binding sites. Further, we find that stable RecF protein-dsDNA complexes are obtained in the presence of ATP or ATP-gamma-S [adenosine-5'-O-(3-thio-triphosphate)]. No other nucleoside triphosphates served as necessary cofactors for dsDNA binding, indicating that RecF is an ATP dependent dsDNA-binding protein. Since a mutation in a putative phosphate-binding motif of RecF protein results in a recF mutant phenotype (S. J. Sandler, B. Chackerian, J. T. Li, and A. J. Clark, Nucleic Acids Res. 20:839-845, 1992), we suggest on the basis of our data that the interactions of RecF protein with ATP, with dsDNA, or with both are physiologically important for understanding RecF protein function in vivo. PMID- 1447140 TI - Cloning and sequencing of a gene encoding a 21-kilodalton outer membrane protein from Bordetella avium and expression of the gene in Salmonella typhimurium. AB - Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21 kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21 kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2 kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the Asd+ vector pYA292, and the construct was introduced into the avirulent delta cya delta crp delta asd S. typhimurium chi 3987 for oral immunization of birds. The gene encoding the 21-kDa protein was expressed equivalently in B. avium 197, delta asd E. coli chi 6097, and S. typhimurium chi 3987 and was localized primarily in the cytoplasmic membrane and outer membrane. In preliminary studies on oral inoculation of turkey poults with S. typhimurium chi 3987 expressing the gene encoding the B. avium 21-kDa protein, it was determined that a single dose of the recombinant Salmonella vaccine failed to elicit serum antibodies against the 21-kDa protein and challenge with wild type B. avium 197 resulted in colonization of the trachea and thymus with B. avium 197. PMID- 1447141 TI - The gene coding for 3-deoxy-manno-octulosonic acid transferase and the rfaQ gene are transcribed from divergently arranged promoters in Escherichia coli. AB - The gene kdtA in Escherichia coli codes for 3-deoxy-D-manno-octulosonic acid transferase, the enzyme responsible for attachment of the two 3-deoxy-D-manno octulosonic acid residues that constitute the link between lipid A and the core oligosaccharide of the lipopolysaccharide. Cloning and subsequent sequencing of the region upstream of kdtA revealed an open reading frame identified as the first gene (rfaQ) in an rfa gene cluster. The kdtA and rfaQ transcripts were identified, and the 5' ends of the transcripts were mapped by primer extension. Two main, divergently arranged promoters were found. These promoters generated transcripts with 5' ends separated by 289 bases. That the two divergent transcripts from the identified promoters represent the kdtA and rfaQ transcripts was confirmed by fusing different parts of the intergenic region between the promoterless lacZ and phoA genes in promoter-screening plasmid pCB267. PMID- 1447142 TI - Differential activities of bacteriophage depolymerase on bacterial polysaccharide: binding is essential but degradation is inhibitory in phage infection of K1-defective Escherichia coli. AB - Host range mutants were derived from bacteriophages PK1A and PK1E specific for the K1 polysialic acid capsule of Escherichia coli. The mutants were selected for their ability to infect E. coli bacteria with a low level of the K1 capsule. A specific loss of the cleaving activity of the phage endosialidase was observed in all the mutants, while the ability to bind specifically to the polysialic acid capsule was retained. The results indicate that the polysaccharide-binding activity of the bacteriophage enzyme is essential for the infection process. The cleaving activity, in contrast, is required for the penetration of the dense polysaccharide of wild-type bacteria but is inhibitory in the infection of bacteria with a sparse capsular polysaccharide. PMID- 1447143 TI - Derivation of a physical map of the chromosome of Bordetella pertussis Tohama I. AB - We have used pulsed-field gel electrophoresis to derive a restriction map of the chromosome of Bordetella pertussis for the enzymes XbaI, SpeI, PacI, and PmeI, which cleave 25, 16, 2, and 1 times, respectively. The apparent size of the genome is 3,750 kb. The positions of genes for major virulence determinants in the vir regulon and of some housekeeping genes were determined. Apart from the previously known linkage of the vir and fha loci, no significant linkage of virulence genes was demonstrated. PMID- 1447144 TI - Cloning of the Escherichia coli sor genes for L-sorbose transport and metabolism and physical mapping of the genes near metH and iclR. AB - The sor genes for L-sorbose (Sor) degradation of Escherichia coli EC3132, a wild type strain, have been cloned on a 10.8-kbp fragment together with parts of the metH gene. The genes were mapped by restriction analysis, by deletion mapping, and by insertion mutagenesis with Tn1725. Seven sor genes with their corresponding gene products have been identified. They form an operon (gene order sorCpCDFBAME) inducible by L-sorbose, and their products have the following functions: SorC (36 kDa), regulatory protein with repressor-activator functions; SorD (29 kDa), D-glucitol-6-phosphate dehydrogenase; SorF and SorB (14 and 19 kDa, respectively), and SorA and SorM (27 and 29 kDa, respectively), two soluble and two membrane-bound proteins, respectively, of an L-sorbose phosphotransferase transport system; SorE (45 kDa), sorbose-1-phosphate reductase. The sor operon from E. coli EC3132 thus is identical to the operon from Klebsiella pneumoniae KAY2026. On the basis of restriction mapping followed by Southern hybridization experiments, the sor genes were mapped at 91.2 min on the chromosome, 3.3 kbp downstream of the metH-iclR gene cluster, and shown to be transcribed in a counterclockwise direction. The chromosomal map of the Sor+ strain EC3132 differs from that of the Sor- strain K-12 in approximately 8.6 kbp. PMID- 1447145 TI - Elucidation of the complete Azorhizobium nicotinate catabolism pathway. AB - A complete pathway for Azorhizobium caulinodans nicotinate catabolism has been determined from mutant phenotype analyses, isolation of metabolic intermediates, and structural studies. Nicotinate serves as a respiratory electron donor to O2 via a membrane-bound hydroxylase and a specific c-type cytochrome oxidase. The resulting oxidized product, 6-hydroxynicotinate, is next reduced to 1,4,5,6 tetrahydro-6-oxonicotinate. Hydrolytic ring breakage follows, with release of pyridine N as ammonium. Decarboxylation then releases the nicotinate C-7 carboxyl group as CO2, and the remaining C skeleton is then oxidized to yield glutarate. Transthioesterification with succinyl coenzyme A (succinyl-CoA) yields glutaryl CoA, which is then oxidatively decarboxylated to yield crotonyl-CoA. As with general acyl beta oxidation, L-beta-hydroxybutyryl-CoA, acetoacetyl-CoA, and finally two molecules of acetyl-CoA are produced. In sum, nicotinate is catabolized to yield two CO2 molecules, two acetyl-CoA molecules, and ammonium. Nicotinate catabolism stimulates Azorhizobium N2 fixation rates in culture. Nicotinate catabolism mutants still able to liberate pyridine N as ammonium retain this capability, whereas mutants so blocked do not. From, mutant analyses and additional physiological tests, N2 fixation stimulation is indirect. In N limited culture, nicotinate catabolism augments anabolic N pools and, as a consequence, yields N2-fixing cells with higher dinitrogenase content. PMID- 1447146 TI - Roles of CatR and cis,cis-muconate in activation of the catBC operon, which is involved in benzoate degradation in Pseudomonas putida. AB - In Pseudomonas putida, the catBC operon encodes enzymes involved in benzoate degradation. Previous studies have determined that these enzymes are induced when P. putida is grown in the presence of benzoate. Induction of the enzymes of the catBC operon requires an intermediate of benzoate degradation, cis,cis-muconate, and a regulatory protein, CatR. It has been determined that CatR binds to a 27-bp region of the catBC promoter in the presence or absence of inducer. We have called this the repression binding site. In this study, we used a gel shift assay to demonstrate that the inducer, cis,cis-muconate, increases the affinity of CatR for the catBC promoter region by 20-fold. Furthermore, in the absence of cis,cis muconate, CatR forms two complexes in the gel shift assay. The inducer cis,cis muconate confers specificity primarily for the formation of complex 2. DNase I footprinting showed that an additional 27 bp of the catBC promoter region is protected by CatR in the presence of cis,cis-muconate. We have named this second binding site the activation binding site. Methylation interference footprinting determined that in the presence or absence of inducer, five G nucleotides of the catBC promoter region were necessary for CatR interaction with the repression binding site, while a single G residue was important for CatR interaction with the activation binding site in the presence of cis,cis-muconate. Using polymerase chain reaction-generated constructs, we found that the binding of CatR to the repression binding site is independent of the activation binding site. However, binding of CatR to the activation binding site required an intact repression binding site. PMID- 1447147 TI - Environmental conditions affect transcription of the pectinase genes of Erwinia chrysanthemi 3937. AB - To depolymerize plant pectin, the phytopathogenic enterobacterium Erwinia chrysanthemi produces a series of enzymes which include a pectin-methyl-esterase encoded by the pem gene and five isoenzymes of pectate lyases encoded by the five genes pelA, pelB, pelC, pelD, and pelE. We have constructed transcriptional fusions between the pectinase gene promoters and the uidA gene, encoding beta glucuronidase, to study the regulation of these E. chrysanthemi pectinase genes individually. The transcription of the pectinase genes is dependent on many environmental conditions. All the fusions were induced by pectic catabolic products and responded, to different degrees, to growth phase, catabolite repression, temperature, and nitrogen starvation. Transcription of pelA, pelD, and pelE was also increased in anaerobic growth conditions. High osmolarity of the culture medium increased expression of pelE but decreased that of pelD; the other pectinase genes were not affected. The level of expression of each gene was different. Transcription of pelA was very low under all growth conditions. The expression of the pelB, pelC, and pem genes was intermediate. The pelE gene had a high basal level of expression. Expression of pelD was generally the most affected by changes in culture conditions and showed a low basal level but very high induced levels. These differences in the expression of the pectinase genes of E. chrysanthemi 3937 presumably reflect their role during infection of plants, because the degradation of pectic polymers of the plant cell walls is the main determinant of tissue maceration caused by soft rot erwiniae. PMID- 1447148 TI - Role of methionine and formylation of initiator tRNA in initiation of protein synthesis in Escherichia coli. AB - We showed recently that a mutant of Escherichia coli initiator tRNA with a CAU- >CUA anticodon sequence change can initiate protein synthesis from UAG by using formylglutamine instead of formylmethionine. We further showed that coupling of the anticodon sequence change to mutations in the acceptor stem that reduced Vmax/Km(app) in formylation of the tRNAs in vitro significantly reduced their activity in initiation in vivo. In this work, we have screened an E. coli genomic DNA library in a multicopy vector carrying one of the mutant tRNA genes and have found that the gene for E. coli methionyl-tRNA synthetase (MetRS) rescues, partially, the initiation defect of the mutant tRNA. For other mutant tRNAs, we have examined the effect of overproduction of MetRS on their activities in initiation and their aminoacylation and formylation in vivo. Some but not all of the tRNA mutants can be rescued. Those that cannot be rescued are extremely poor substrates for MetRS or the formylating enzyme. Overproduction of MetRS also significantly increases the initiation activity of a tRNA mutant which can otherwise be aminoacylated with glutamine and fully formylated in vivo. We interpret these results as follows. (i) Mutant initiator tRNAs that are poor substrates for MetRS are aminoacylated in part with methionine when MetRS is overproduced. (ii) Mutant tRNAs aminoacylated with methionine are better substrates for the formylating enzyme in vivo than mutant tRNAs aminoacylated with glutamine. (iii) Mutant tRNAs carrying formylmethionine are significantly more active in initiation than those carrying formylglutamine. Consequently, a subset of mutant tRNAs which are defective in formylation and therefore inactive in initiation when they are aminoacylated with glutamine become partially active when MetRS is overproduced. PMID- 1447149 TI - Escherichia coli B lacks one of the two initiator tRNA species present in E. coli K-12. AB - We show that the metY locus which specifies tRNA(2fMet) in Escherichia coli K-12 specifies tRNA(1fMet) in E. coli B. This conclusion is based on results of Southern blot analysis of E. coli B and K-12 DNAs and on polymerase chain reaction amplification, cloning, and sequencing of an approximately 200-bp region of DNA corresponding to the metY loci of E. coli B and E. coli K-12. We also show that the metY locus of E. coli B is transcriptionally active. E. coli strains transformed with the multicopy plasmid vector pUC19 carrying the metY locus of E. coli B overproduce tRNA(1fMet) in E. coli B and E. coli K-12 in contrast to strains transformed with pUC19 carrying the corresponding locus from E. coli K 12, which overproduce tRNA(2fMet). PMID- 1447150 TI - The a locus governs cytoduction in Ustilago maydis. AB - We have developed a cytoduction assay to measure cell fusion quantitatively in the basidiomycete corn smut fungus Ustilago maydis. This assay employs a mutation conferring resistance to oligomycin that exhibits non-Mendelian inheritance and presumably affects the mitochondrial genome. After auxotrophic olir cells are mixed with prototrophic olis cells, prototrophic olir cells can be detected at a significant frequency after several hours of incubation, reaching a maximum of 10% of the total prototrophs in the mixture after 18 h. We demonstrate that this cell fusion event occurs only if the mating partners have different alleles of the a mating-type locus and is not influenced by the b locus. These studies support the view that the a locus but not the b locus controls establishment of the filamentous, pathogenic state. PMID- 1447151 TI - The Dictyostelium discoideum spore germination-specific cellulase is organized into functional domains. AB - During Dictyostelium discoideum spore germination, degradation of the cellulose containing spore wall is required to allow the amoeba to emerge. The CelA gene, which is transcribed and expressed exclusively during spore germination, codes for a 705-amino-acid protein that has cellulase activity [endo-(1,4)-beta-D glucanase]. Amoebae transformed by a vector containing the CelA coding sequence or portions of it transcribed from a heterologous promoter expressed and secreted full-length or suitably truncated proteins during vegetative growth when, under normal conditions, these proteins are not made. The gene constructs divided the CelA protein into three domains: a 461-amino-acid N-terminal region that has significant similarity to those of other cellulases and that has been shown to be the catalytic domain; a contiguous 91-residue repeat containing the motif threonine-glutamic acid-threonine-proline, which is glycosylated; and, joined to the repeat, a C-terminal 153-amino-acid sequence that most probably defines a cellulose-binding domain. PMID- 1447152 TI - Cell surface carbohydrates of microaerobic, nitrogenase-active, continuous cultures of Bradyrhizobium sp. strain 32H1. AB - A continuous culture system was developed to examine the cell surface carbohydrates of Bradyrhizobium sp. strain 32H1. When cultures were shifted from aerobic to microaerobic growth conditions, nitrogenase activity was induced and extracellular polysaccharide levels were greatly reduced; however, the levels of cell-associated cyclic beta-1,6 -1,3 glucans were found to be essentially unchanged. PMID- 1447153 TI - Escherichia coli mraR gene involved in cell growth and division. AB - The mraR gene, which has a coding frame of 363 bp and lies close to and upstream of the ftsI gene of Escherichia coli, is involved in both cell division and cell lysis. It is thought to function in regulating the two distinct steps of the cell cycle, as two different one-base mutations in this unique gene caused different phenotypical changes in the cell. Comparison of nucleotide sequences of the mutant type mraR DNAs with the wild type suggested that filamentation of the cell was caused by a mutation in the putative start codon, whereas lysis of the cell was caused by a mutation which led to a change of one internal glutamate residue to lysine. PMID- 1447154 TI - Multiple antibiotic susceptibility associated with inactivation of the prc gene. AB - A Tn5 insertion which led to increased susceptibility to multiple drugs, including tetracycline, chloramphenicol, nalidixic acid, erythromycin, spectinomycin, norfloxacin, and novobiocin, was identified in Escherichia coli. Cloning and sequence studies showed that the insertion was in the previously identified prc gene at min 40.4. The prc product is known to function as a protease linked to processing of penicillin-binding protein 3 and lambda repressor and when absent to allow some leakage of periplasmic constituents. Complementation studies with the prc gene on plasmids showed complete recovery of parental levels of susceptibility to all drugs except chloramphenicol, with which only partial reversion to wild-type levels was observed. PMID- 1447155 TI - A second gene for a secreted aspartate proteinase in Candida albicans. AB - The gene (PRA11) encoding a secreted aspartate proteinase of Candida albicans has been cloned and sequenced. The nucleotide and deduced amino acid sequences of PRA11 are 77 and 73% identical, respectively, with the reported sequences of PRA10 also cloned from C. albicans. Southern analyses indicated that the genome of each strain examined (ATCC 10231 and ATCC 10261) contains PRA10 and PRA11. Northern (RNA) analyses showed that PRA11 was expressed at a much higher level than was PRA10 when secretion of the proteinase by strain ATCC 10261 was induced with albumin. PMID- 1447156 TI - TerF, the sixth identified replication arrest site in Escherichia coli, is located within the rcsC gene. AB - We report the existence of a sixth replication arrest site, TerF, that is located within the coding sequences of the rcsC gene, a negative regulator of capsule biosynthesis. The TerF site is oriented to allow transcription of the rcsC gene but prevent DNA replication in the terminus-to-origin direction. Our results demonstrate that the TerF site is functional in both chromosomal and plasmid environments and that the stability of the Tus-TerF protein-DNA complex more closely resembles the plasmid R6K Ter sites than the chromosomal TerB site. PMID- 1447157 TI - Identification of the gene encoding transcription factor NusG of Thermus thermophilus. AB - The nusG gene of Thermus thermophilus HB8 was cloned and sequenced. It is located 388 bp downstream from tufB, which is followed by the genes for ribosomal proteins L11 and L1. No equivalent to secE preceding nusG, as in Escherichia coli, could be detected. The nusG gene product was overproduced in E. coli. A rabbit antiserum raised against the purified recombinant NusG reacted exclusively with one protein band of T. thermophilus crude extracts in Western blot (immunoblot) analyses, and no cross-reaction of the antiserum with E. coli NusG was observed. Recombinant NusG and the reacting T. thermophilus wild-type protein had identical sizes on sodium dodecyl sulfate-polyacrylamide gels. T. thermophilus and E. coli NusG have 45% identical and 22.5% similar amino acids, and similarities between the two proteins are most pronounced in carboxy-terminal regions. The T. thermophilus nusG gene could not rescue a nusG-deficient E. coli mutant strain. PMID- 1447158 TI - HMf, a histone-related protein from the hyperthermophilic archaeon Methanothermus fervidus, binds preferentially to DNA containing phased tracts of adenines. AB - HMf, a histone-related protein from Methanothermus fervidus, was found to bind preferentially to a DNA that is intrinsically bent as a result of the presence of phased oligo(dA) tracts. The intergenic regions in M. fervidus DNA are A+T rich and frequently contain oligo(dA) tracts, some of which may have the size and phasing required to create a net bending in one direction. The binding of HMf to bent DNA could play a direct role in gene expression and stabilization of the genome of this organism. PMID- 1447159 TI - Cloning and characterization of an aminoglycoside resistance determinant from Micromonospora zionensis. AB - The sisomicin-gentamicin resistance methylase (sgm) gene was isolated from Micromonospora zionensis and cloned in Streptomyces lividans. The sgm gene was expressed in Micromonospora melanosporea, where its own promoter was active, and also in Escherichia coli under the control of the lacZ promoter. The complete nucleotide sequence of 1,122 bp and a transcription start point were determined. The sequence contains an open reading frame that encodes a polypeptide of 274 amino acids. The methylation of 30S ribosomal subunits by Sgm methylase accounts adequately for all known resistance characteristics of M. zionensis, but expression of high-level resistance to hygromycin B is background dependent. A comparison of the amino acid sequence of the predicted Sgm protein with the deduced amino acid sequences for the 16S rRNA methylases showed extensive similarity of Grm and significant similarity to KgmB but not to KamB methylase. PMID- 1447160 TI - Physical locations of genes in the rne (ams)-rpmF-plsX-fab region of the Escherichia coli K-12 chromosome. PMID- 1447161 TI - Physical map location of the Escherichia coli gene encoding acyl coenzyme A synthetase. PMID- 1447162 TI - Physical map of the oxyR-trmA region (minute 89.3) of the Escherichia coli chromosome. PMID- 1447163 TI - Genetic and physical clarification of the Escherichia coli genetic map in the 76.5-minute essential gene cluster containing heat shock and cell division genes. PMID- 1447164 TI - Location of the protease II gene (ptrB) on the physical map of the Escherichia coli chromosome. PMID- 1447165 TI - Physical map location of the narQ gene of Escherichia coli. PMID- 1447166 TI - Function of Ras as a molecular switch in signal transduction. PMID- 1447167 TI - A mouse CDC25-like product enhances the formation of the active GTP complex of human ras p21 and Saccharomyces cerevisiae RAS2 proteins. AB - GDP-dissociation stimulators (GDSs) are the key element for the regeneration of the active state of ras proteins, but despite intensive investigations, little is so far known about their functional and structural properties, particularly in mammals. A growing number of genes from various organisms have been postulated to encode GDSs on the basis of sequence similarity with the Saccharomyces cerevisiae CDC25 gene, whose product acts as a GDS of RAS proteins. However, except for CDC25 and the related SDC25 C-domain, no biochemical evidence of ras GDS activity for these CDC25-like proteins has yet been available. We show that the product of a recently isolated mouse CDC25-like gene (CDC25Mm) can strongly enhance (more than 1000 times) the GDP release from both human c-Ha-ras p21 and yeast RAS2 in vitro. As a consequence, the CDC25Mm induces a rapid formation of the biologically active Ras.GTP complex. This GDS is much more active on the GDP than on the GTP complex and has a narrow substrate specificity, since it was found to be inactive on several ras-like proteins. The mouse GDS can efficiently substitute for yeast CDC25 in an in vitro adenylylcyclase assay on RAS2 cdc25 yeast membranes. Our results show that a cloned GDP to GTP exchange factor of mammalian ras belongs to the novel family of CDC25-like proteins. PMID- 1447168 TI - Lateral lipid distribution is a major regulator of lipase activity. Implications for lipid-mediated signal transduction. AB - Pancreatic carboxylester lipase catalyzes the exchange of 18O between water and 13,16-cis,cis-doco-sadienoic acid (DA) in monolayers at the argon-buffer interface (Muderhwa, J.M., Schmid, P.C., and Brockman, H.L. (1992) Biochemistry 31, 141). In mixed monolayers of 18O, 18O-DA and 1-palmitoyl-2-oleoyl-sn-glycero 3-phosphocholine (POPC), both the extent and mechanism of 18O exchange show characteristics of a critical transition in the range of 0.5-0.6 mol fraction of DA (Muderhwa, J.M., and Brockman, H. L. (1992) Biochemistry 31, 149). To determine if the regulatory behavior exhibited on this type of surface is limited to members of the carboxylester lipase gene family (cholinesterases), comparable experiments were performed with a genetically and functionally unrelated lipase, pancreatic colipase-dependent lipase (PL). PL readily catalyzed the exchange of 18O between water and the carboxyl group of DA with enzyme at either monolayer or catalytic levels in the fatty acid-buffer interface. The oxygen exchange reaction obeyed a random, sequential mechanism, indicating that the dissociation of the enzyme.DA complex is much faster than the rate-limiting step in the overall exchange process. Kinetic analysis of oxygen exchange in pure DA monolayers showed a first-order dependence on interfacial PL and DA concentrations from which kcat/Km values were calculated. The oxygen exchange reaction proceeded with a rate constant of 16 x 10(-2) cm2 pmol-1 s-1, a value comparable to that for hydrolysis of the ester substrate, 1,3-dioleoylglycerol. With a monolayer of PL adsorbed to the interfacial phase, kcat/Km for oxygen exchange was about 600-fold lower than the value obtained with catalytic levels of adsorbed enzyme, indicating a possible restriction of substrate diffusion in the protein-covered fatty acid monolayer. With constant bulk PL concentration and mixed lipid monolayers containing DA and the non-substrate lipid, POPC, the extent of oxygen exchange increased abruptly as the abundance of DA in the interface was increased from 0.5 to 0.6 mol fraction. Concomitant with this critical transition was a change in the apparent mechanism of oxygen exchange from coupled to random, sequential. For both the extent of oxygen exchange and its mechanism shift, the critical transition was independent of the lipid packing density, i.e. surface pressure, of the interface. These results show that PL responds similarly to carboxylester lipase with respect to changes in interfacial lipid mole fraction in DA-POPC surfaces.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1447169 TI - Analysis of the perturbation of phospholipid model membranes by rhodanese and its presequence. AB - The ability of the cytoplasmically synthesized mitochondrial enzyme rhodanese and its putative import signal sequence to interact with model phospholipid membranes was characterized. Membrane perturbation assays were used to test a current hypothesis that the initial step in protein translocation may involve binding of signal sequences with membrane lipids. Here we show comparative studies on the effect of native and various forms of denatured rhodanese, as well as two peptides, rho(1-23) and rho(11-23), derived from its NH2-terminal sequence, on the perturbation of 6-carboxyfluorescein-containing large unilamellar vesicles composed of either cardiolipin, phosphatidylcholine, or phosphatidylserine. We monitored the degree of perturbation by measuring dye leakage and found differential perturbation by either peptide or protein. Unfolded rhodanese perturbed vesicles in the order phosphatidylserine > cardiolipin >> phosphatidylcholine. Denatured rhodanese was approximately 25 times more effective (on a molar basis) than rho(1-23) in the disruption of anionic liposomes. Rho(11-23) was unable to perturb liposomes. We found an inverse correlation between degree of activity of rhodanese folding intermediates and their ability to perturb liposomes. On urea denaturation, enzymatic activity was completely lost before membrane perturbation ability reached significant levels. Analysis of the peptides by circular dichroism showed that anionic liposomes can induce alpha-helical structure only in rho(1-23) and denatured rhodanese. Intrinsic peptide fluorescence studies showed that only rho(1-23) and denatured rhodanese partitioned into these model membranes. Results obtained here imply that peptides from naturally occurring alpha-helical structures may need adjacent motifs for helical structure induction in lipid environments, and the subsequent secondary structure may, in turn, promote partitioning of these segments into the lipid phase and ultimately lead to membrane perturbation. PMID- 1447170 TI - Nonenzymatic glycation of type I collagen. The effects of aging on preferential glycation sites. AB - The present study was designed to investigate the effects of aging on preferential sites of glucose adduct formation on type I collagen chains. Two CNBr peptides, one from each type of chain in the type I tropocollagen molecule, were investigated in detail: alpha 1(I)CB3 and alpha 2CB3-5. Together these peptides comprise approximately 25% of the total tropocollagen molecule. The CNBr peptides were purified from rat tail tendon, obtained from animals aged 6, 18, and 36 months, by ion exchange chromatography, gel filtration, and high performance liquid chromatography (HPLC). Sugar adducts were radiolabeled by reduction with NaB3H4. Glycated tryptic peptides were prepared from tryptic digests of alpha 2CB3-5 and alpha 1(I)CB3 by boronate affinity chromatography and HPLC. Peptides were identified by sequencing and by compositional analysis. Preferential sites of glycation were observed in both CB3 and alpha 2CB3-5. Of the 5 lysine residues in CB3, Lys-434 was the favored glycation site. Of the 18 lysine residues and 1 hydroxylysine residue in alpha 2CB3-5, 3 residues (Lys-453, Lys-479, and Lys-924) contained more than 80% of the glucose adducts on the peptide. Preferential glycation sites were highly conserved with aging. In collagen that had been glycated in vitro, the relative distribution of glucose adducts in old animals differed from that of young animals. In vitro experiments suggest that primary structure is the major determinant of preferential glycation sites but that higher order structure may influence the relative distribution of glucose adducts among these preferred sites. PMID- 1447171 TI - Organization of phosphatidylcholine and sphingomyelin in the surface monolayer of low density lipoprotein and lipoprotein(a) as determined by time-resolved fluorometry. AB - Fluorescent analogs of phosphatidylcholine (PC) and sphingomyelin (SM) labeled with diphenylhexatrienylpropionic acid (DPH) were prepared and incorporated into the surface layer of human low density lipoprotein (LDL) and lipoprotein(a) (Lp(a)). Fluorescence anisotropy measurements of DPH-PC and DPH-SM in both lipoprotein classes were carried out at different temperatures ranging from 20 to 37 degrees C. DPH-PC as well as DPH-SM were shown to reside in more rigid domains in Lp(a) than in LDL according to higher anisotropy values in Lp(a). In both LDL and Lp(a), DPH-PC experienced a more rigid environment than DPH-SM, suggesting different environments of PC and SM in the surface shell of the lipoproteins. Fluorescence lifetimes of the labeled lipoproteins were determined by phase and modulation fluorometry. We found bimodal Lorentzian distributions for the decay times of DPH-PC and DPH-SM in LDL and Lp(a). Lifetime distribution centers for labeled lipids were very similar except for DPH-PC in Lp(a) which was shifted to longer lifetimes, suggesting a less polar environment of PC in Lp(a) than in LDL. The distributional width of DPH-PC in Lp(a) was broader than in LDL. Accordingly, phosphatidylcholine must be localized in a more homogeneous environment in LDL as compared with Lp(a). On the other hand, no difference in distributional widths was observed for DPH-SM in both lipoproteins, showing that SM organization in Lp(a) is unaffected by apo(a). From the obtained fluorescence data we propose that apoproteins discriminate between the choline phospholipids and preferentially associate with phosphatidylcholine. This effect is enhanced in Lp(a) due to the presence of apolipoprotein(a). PMID- 1447172 TI - Purification and ligand binding of a soluble class I major histocompatibility complex molecule consisting of the first three domains of H-2Kd fused to beta 2 microglobulin expressed in the baculovirus-insect cell system. AB - A recombinant baculovirus encoding a single-chain murine major histocompatibility complex class I molecule in which the first three domains of H-2Kd are fused to beta 2-microglobulin (beta 2-m) via a 15-amino acid linker has been isolated and used to infect lepidopteran cells. A soluble, 391-amino acid single-chain H-2Kd (SC-Kd) molecule of 48 kDa was synthesized and glycosylated in insect cells and could be purified in the absence of detergents by affinity chromatography using the anti-H-2Kd monoclonal antibody SF1.1.1.1. We tested the ability of SC-Kd to bind antigenic peptides using a direct binding assay based on photoaffinity labeling. The photoreactive derivative was prepared from the H-2Kd-restricted Plasmodium berghei circumsporozoite protein (P.b. CS) peptide 253-260 (YIPSAEKI), a probe that we had previously shown to be unable to bind to the H-2Kd heavy chain in infected cells in the absence of co-expressed beta 2-microglobulin. SC Kd expressed in insect cells did not require additional mouse beta 2-m to bind the photoprobe, indicating that the covalently attached beta 2-m could substitute for the free molecule. Similarly, binding of the P.b. CS photoaffinity probe to the purified SC-Kd molecule was unaffected by the addition of exogenous beta 2-m. This is in contrast to H-2KdQ10, a soluble H-2Kd molecule in which beta 2-m is noncovalently bound to the soluble heavy chain, whose ability to bind the photoaffinity probe is greatly enhanced in the presence of an excess of exogenous beta 2-m. The binding of the probe to SC-Kd was allele-specific, since labeling was selectively inhibited only by antigenic peptides known to be presented by the H-2Kd molecule. PMID- 1447173 TI - Hirudisins. Hirudin-derived thrombin inhibitors with disintegrin activity. AB - Recombinant hirudin variants have been designed which inhibit alpha-thrombin by the hirudin mechanism and which in addition exhibit disintegrin activity. These proteins, called "hirudisins," have been engineered by replacing the Ser-Asp-Gly Glu sequence at the tip of hirudin's finger-like structure (residues 32-35) by Arg-Gly-Asp-Ser (RGDS) to yield hirudisin and Lys-Gly-Asp-Ser (KGDS) to obtain hirudisin-1. Comparison of thrombin inhibition activities showed that hirudisin is 2-fold more potent (K(i) = 160 +/- 70 fM) than hirudisin-1 (K(i) = 370 +/- 44 fM) and recombinant (r)-hirudin (K(i) = 270 +/- 50 fM). alpha-Thrombin-stimulated platelet aggregation was effectively inhibited by r-hirudin, hirudisin, and hirudisin-1 with IC50 of 5.7 to 6.8 nM. Unlike r-hirudin, hirudisin inhibits ADP induced platelet aggregation (IC50 = 65 microM) 3- to 5-fold stronger than the linear GRGDS- and RGDS-peptide. Direct interaction of hirudisin with purified glycoprotein IIb-IIIa demonstrated that antiplatelet aggregation activity is due to the integrin-directed RGD motif. Disintegrin activity of hirudisin relative to that of reduced and carboxymethylated hirudisin suggests that the conformational strain favors binding to integrins. On the basis of these results, hirudisins appear to be interesting molecules for the design of potential antithrombotic agents with antithrombin as well as antiplatelet aggregation activities. PMID- 1447174 TI - Polymerization of secretory IgM in B lymphocytes is prevented by a prior targeting to a degradation pathway. AB - B lymphocytes express on their surface a membrane form of IgM (mIgM), and synthesize but fail to secrete a secretory form of IgM (sIgM). Plasma cells shift to the exclusive synthesis and efficient secretion of sIgM. The sIgM in B cells differs from that in plasma cells in its pattern of assembly: in plasma cells, monomers of sIgM are assembled into polymers and only polymers are secreted; in B lymphocytes, monomeric sIgM is neither polymerized nor secreted and is degraded intracellularly. In this article we blocked the export of proteins from the endoplasmic reticulum at low temperatures or with energy poisons or brefeldin A, and localized the different assembly steps of mIgM and sIgM in the 38C B lymphocytes and of sIgM in the 38C-derived sIgM-secreting D2 hybridoma. In both cell lines, sIgM assembly into monomers was not affected, whereas polymerization of sIgM in D2 cells and monomer formation of mIgM in 38C cells were strongly inhibited. Moreover, probing with specific lectins revealed galactosylated monomers and polymers in D2 cells and galactosylated hemimer and monomers only of mIgM in 38C cells. In addition, when Golgi functions were hampered with Tris base, monomerization of mIgM and polymerization of sIgM were attenuated. These results indicate that polymerization of sIgM in D2 cells and monomerization of mIgM in 38C cells are post-endoplasmic reticulum events, occurring in or beyond the trans-Golgi galactosylation compartment. Since only polymers are secreted from D2 cells and only monomeric mIgM is displayed on the surface of 38C cells, partially assembled molecules may traverse the secretory pathway yet are restricted from the cell surface. Furthermore, monomeric sIgM in 38C cells is never galactosylated, thus it is degraded prior to the galactosylation compartment. We conclude that targeting of sIgM to degradation in 38C cells precedes its assembly site into polymers in D2 cells. This implies that degradation of sIgM does not result from the incompetence of 38C cells to polymerize. Rather, assembly of sIgM into polymers and their subsequent secretion are prevented in B lymphocytes by preceding targeting of monomeric sIgM to degradation. PMID- 1447175 TI - Functional differences between manganese and iron superoxide dismutases in Escherichia coli K-12. AB - Superoxide dismutases are enzymes that defend against oxidative stress through decomposition of superoxide radical. Escherichia coli contains two highly homologous superoxide dismutases, one containing manganese (MnSOD) and the other iron (FeSOD). Although E. coli Mn and FeSOD catalyze the dismutation of superoxide with comparable rate constants, it is not known if they are physiologically equivalent in their protection of cellular targets from oxyradical damage. To address this issue, isogenic strains of E. coli containing either Mn or FeSOD encoded on a plasmid and under the control of tac promoter were constructed. SOD specific activity in the Mn and FeSOD strains could be controlled by the concentration of isopropyl beta-thiogalactoside in the medium. The tolerance of these strains to oxidative stress was compared at equal Mn and FeSOD specific activities. Our results indicate that E. coli Mn and FeSOD are not functionally equivalent. The MnSOD is more effective than FeSOD in preventing damage to DNA, while the FeSOD appears to be more effective in protecting a cytoplasmic superoxide-sensitive enzyme. These data are the first demonstration that Mn and FeSOD are adapted to different antioxidant roles in E. coli. PMID- 1447176 TI - The effect of fibrin structure on fibrinolysis. AB - Fibrin structure contributes to the regulation of the fibrinolytic rate. As the fibrin fiber size is decreased, the fibrinolytic rate also decreases. Fibrin structure was altered by either changing the ratio of thrombin to fibrinogen, i.e. altering the assembly rate or by adding a fibrin assembly inhibitor, iopamidol. Changes in the fibrinolytic rate were followed by measuring the time dependence of the decrease in the fiber mass/length ratio during fibrinolysis. A measure of the overall fibrinolytic rate was determined from the decrease in the mass/length ratio versus time. An 8-fold reduction in the fibrinolytic rate was seen on decreasing the mass/length ratio from 2.7 x 10(12) daltons/cm to 0.5 x 10(12) daltons/cm. It is shown that thin fibrin fibers have a decreased rate of conversion of plasminogen to plasmin by tissue plasminogen activator and that thin fibrin fibers are lysed more slowly than thick fibrin fibers. PMID- 1447177 TI - Structural characterization of a novel class of glycophosphosphingolipids from the protozoan Leptomonas samueli. AB - Aqueous phenol extraction of the lower trypanosomatid Leptomonas samueli released into the aqueous layer a chloroform/methanol/water-soluble glycophosphosphingolipid fraction. Alkaline degradation and purification by gel filtration chromatography resulted in a tetrasaccharide (phosphatidylinositol (PI)-oligosaccharide A), and a pentasaccharide (PI-oligosaccharide B), each containing 2 mol of 2-aminoethylphosphonate and 1 mol of phosphate. Nuclear magnetic resonance spectroscopy and fast atom bombardment-mass spectrometry suggested that the structure of PI-oligosaccharide A is [formula: see text] and that of PI-oligosaccharide B is as shown. [formula: see text] Both compounds contain an inositol unit linked to ceramide via a phosphodiester bridge. The major aliphatic components of the ceramide portion are stearic acid, lignoceric acid, and C20-phytosphingosine. These novel glycolipids fall within the glycosylated phosphatidylinositol (GPI) family, since they contain the core structure Man alpha (1-->4)GlcNH2 alpha (1-->6)myo-inositol-1-PO4, which is also found in the glycoinositolphospholipids and lipophosphoglycan of Leishmania spp., the L. major promastigote surface protease, the glycosylphosphatidylinositol anchor of Trypanosoma brucei variant surface glycoprotein, and the lipopeptidophosphoglycan of Trypanosoma cruzi. The glycophosphosphingolipids of Leptomonas have features in common with the glycolipids of both Leishmania and T. cruzi, resembling the former by the alpha (1-->3) linkage of mannose to the GPI core, while the 2-aminoethylphosphonate substituent on O-6 of glucosamine and the presence of ceramide in place of glycerol lipids is more reminiscent of T. cruzi. Thus these data lend some support to the hypothesis that both T. cruzi and Leishmania evolved from a Leptomonas-like ancestor. PMID- 1447178 TI - Fish egg glycophosphoproteins have species-specific N-linked glycan units previously found in a storage pool of free glycan chains. AB - Recent findings (Ishii, K., Iwasaki, M., Inoue, S., Kenny, P. T. M., Komura, H., and Inoue, Y. (1989) J. Biol. Chem. 264, 1623-1630; Inoue, S., Iwasaki, M., Ishii, K., Kitajima, K., and Inoue, Y. (1989) J. Biol. Chem. 264, 18520-18526) of a relatively large quantity of complex-type free sialo-oligosaccharides in the unfertilized eggs of freshwater fish, Plecoglossus altivelis and Tribolodon hakonensis, prompted us to search for their progenitor glycoproteins. First we demonstrated a third occurrence of free sialoglycans in the unfertilized eggs of Medaka fish (Oryzias latipes). Next, in all three species studied, a uniformly high level of glycophosphoproteins (GPP) was identified and found to possess N linked glycan units. The carbohydrate structures of the GPP were determined to be identical with those of the free glycans isolated from the unfertilized eggs of the respective fish species. Thus, the most likely candidate for the progenitor of free sialoglycans appeared to be the oocyte GPPs. This implies that the liberation of the free glycans by a putative peptide-N4-(N-acetyl-beta glucosaminyl)asparagine amidase may represent a necessary biochemical event during vitellogenesis or oogenesis. The present results may provide insight into a new concept of a "protein N-glycosylation/de-N-glycosylation system" recently proposed by us (Seko, A., Kitajima, K., Inoue, Y., and Inoue, S. (1991) J. Biol. Chem. 266, 22110-22114). PMID- 1447179 TI - Thermodynamic changes in the binding of Ca2+ to a mutant human lysozyme (D86/92). Enthalpy-entropy compensation observed upon Ca2+ binding to proteins. AB - The thermodynamic change in the binding of Ca2+ to a mutant human lysozyme having an engineered Ca2+ binding site (Kuroki, R., Taniyama, Y., Seko, C., Nakamura, H., Kikuchi, M., and Ikehara, M. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 6903 6907) was analyzed by calorimetry and interpreted in terms of structural information obtained from x-ray crystallography. It was found that the enthalpic contribution for the Ca2+ binding reaction was small, driven primarily by entropy release (10 kcal/mol). This release of entropy was also observed in some organic chelators. Moreover, through the information of the tertiary structures of the apo- and holomutant lysozyme, it was confirmed that the entropy release (10 kcal/mol) upon the binding of Ca2+ arises primarily from the release of bound water molecules hydrating the free Ca2+. Previous studies of Ca2+ binding to proteins have involved significant changes in protein conformation. They can now be reevaluated to determine the contribution of conformational changes to Ca2+ binding. After removing the thermodynamic contribution of Ca2+ binding itself, it is found that upon the binding of Ca2+ the enthalpy change is negative but is almost compensated by the negative entropy change. The negative change in both enthalpy and entropy is characteristic of values seen in the thermodynamic change upon the folding of proteins. PMID- 1447180 TI - Analysis of the streptococcal hyaluronic acid synthase complex using the photoaffinity probe 5-azido-UDP-glucuronic acid. AB - The mucopolysaccharide, hyaluronic acid, is an important component of both mammals and pathogenic streptococci. This high molecular weight polymer is synthesized by a membrane-associated, multisubunit hyaluronate synthase which utilizes UDP-glucuronic acid and UDP-N-acetylglucosamine as substrates. Using the photoaffinity probe, [beta-32P]5-azido-UDP-glucuronic acid, three streptococcal membrane proteins (42, 33, and 27 kDa) specifically photoincorporated this probe. Labeling of these proteins was enhanced in the presence of UDP-N acetylglucosamine, whereas UDP-galactose or UDP-glucose had no effect on incorporation. UDP-glucuronic acid inhibited the labeling of the three proteins in a dose-dependent manner. Detergent-solubilized membrane proteins from transposon-inactivated hyaluronic acid capsule mutants no longer incorporated the probe. This was also the case when membranes from stationary phase organisms were tested. Finally, glucuronic acid no longer was incorporated into high molecular weight hyaluronic acid with either the mutant or stationary phase preparations. Further biochemical analysis will be required to demonstrate the exact role each of the proteins play in hyaluronic acid biosynthesis. PMID- 1447181 TI - Isoforms of mammalian ubiquitin-activating enzyme. AB - Ubiquitin-activating enzyme, "E1," is the first enzyme in the pathway leading to formation of ubiquitin-protein conjugates and represents a potential target for regulation in the metabolic control of the conjugation reaction. Antiserum raised against human E1 recognizes two immunoreactive proteins in extracts from several human cell lines and animal tissues. We have characterized these two immunoreactive proteins in HeLa cells and present evidence that they are isoforms of E1. We have designated these isoforms as "E1(110 kDa)" and "E1(117 kDa)" to reflect their apparent molecular masses determined from SDS-polyacrylamide gel electrophoresis. These two immunoreactive proteins are immunologically similar, have nearly identical peptide maps, and comigrate with enzymatic activity characteristic of E1 in native polyacrylamide gel electrophoretic separations. Pulse-labeling experiments reveal that both isoforms are long-lived in vivo with degradation rates which are inconsistent with a proenzyme/enzyme model. Furthermore, their rates of degradation, which vary depending on the cell line studied, are kinetically distinguishable in contact-inhibited human lung fibroblasts. This work represents the first demonstration of E1 isoforms in a non plant species and carries important implications for studies of the regulatory mechanisms controlling ubiquitin conjugation. PMID- 1447182 TI - Regulation of the cellular stress response by reactive electrophiles. The role of covalent binding and cellular thiols in transcriptional activation of the 70 kilodalton heat shock protein gene by nephrotoxic cysteine conjugates. AB - The cytotoxicity of nephrotoxic cysteine conjugates (NCC) in the renal epithelial cell line, LLC-PK1, is due to the covalent binding of a reactive electrophilic metabolite produced from NCC metabolism by cysteine conjugate beta-lyase. Covalent binding of NCC-derived reactive metabolites leads to a cascade of events including depletion of cellular non-protein sulfhydryls, increased cytosolic free calcium, and lipid peroxidation, which is ultimately responsible for cell death. We have used this model to investigate the signalling mechanism(s) through which reactive electrophiles increase synthesis of the 70-kD heat shock protein (HSP70). NCC treatment resulted in increased HSP70 synthesis as well as time- and dose-dependent increases in hsp70 mRNA in LLC-PK1 cells. The induction of hsp70 mRNA was blocked by actinomycin D, and nuclear run-on experiments showed that the hsp70 gene was transcriptionally activated. Inhibition of protein synthesis did not block the increase in hsp70 mRNA or transcriptional activation of the hsp70 gene suggesting that induction occurs due to activation of existing transcription factors. Inhibiting the covalent binding with a beta-lyase inhibitor, aminooxyacetic acid, blocked the increase in hsp70 mRNA. Agents which do not alter binding but do prevent toxicity by blocking the rise in cytosolic free calcium and lipid peroxidation were not effective inhibitors of hsp70 mRNA accumulation. However, the thiol reducing agent, dithiothreitol, inhibited induction of hsp70 mRNA by NCC. The data suggest that covalent binding and alterations in cellular non-protein thiols serve as signals for activation of pre existing transcription factors which increase hsp70 gene expression. It is proposed that reactive electrophiles may have a primary effect on protein conformation resulting in activation of the hsp70 gene. PMID- 1447183 TI - Structural requirements for transport of preprocecropinA and related presecretory proteins into mammalian microsomes. AB - The presecretory protein preprocecropinA (which comprises 64 amino acid residues) as well as a synthetic hybrid between preprocecropinA and dihydrofolate reductase (which comprises 252 amino acid residues) are processed by and transported into mammalian microsomes. Transport of both precursor proteins can take place cotranslationally, i.e. with the aid of ribosome and signal recognition particle, or posttranslationally, i.e. independently of these ribonucleoparticles (RNPs). We investigated the role of the precursor structure with respect to competence for RNP-independent transport by constructing deletion mutants and hybrid proteins. The results demonstrate that the signal peptide is essential for RNP independent transport. Furthermore, the signal peptide is sufficient for translocation of preprocecropinA derivatives up to 85 amino acid residues in size. However, the conformation of the precursor protein is decisive in the case of larger hybrid proteins. PMID- 1447184 TI - Diffusion control in blood coagulation. Activation of factor X by factors IXa/VIIIa assembled on human monocyte membranes. AB - This study examines mechanisms that regulate the activation of blood coagulation proteases on intact cell membranes. The activation of factor X by factors IXa and VIIIa assembled on viable monocytes is presented as a biologically relevant model for membrane-dependent proteolysis of coagulation zymogens. The hypothesis that this reaction is limited by diffusion was tested by comparing predicted with observed concentration dependence, temperature dependence, and effective rate coefficient. Rates of factor X catalysis were measured using a chromogenic substrate specific for the product, factor Xa. The value of KR and of K1/2, i.e. concentrations giving half-maximal rates in reciprocal functional titrations with substrate and enzyme, respectively, were directly correlated with the concentration of the titrated component. Arrhenius plots constructed over temperatures encompassing 10-35 degrees C were biphasic with downward concavity. Apparent activation energies were 6.01 +/- 0.93 and 35.84 +/- 8.9 kcal/mol for the interval above and below the inflection point, respectively. The effective rate coefficient calculated from apparent kinetic parameters was 3.58 +/- 0.1 x 10(12) M-1 s-1. This rate is similar to the maximal rate of collision between factor X molecules and the monocyte, i.e. 2.9 x 10(12) M-1 s-1 estimated from the steady-state von Smoluchowski equation for uniformly reacting spherical particles. The observed agreement between predicted and experimental results indicates that under biologically relevant conditions, the rate of factor X activation by the intrinsic protease is controlled by diffusion of factor X toward the catalytic site. PMID- 1447185 TI - Engineering dehydrated amino acid residues in the antimicrobial peptide nisin. AB - The small antimicrobial peptide nisin, produced by Lactococcus lactis, contains the uncommon amino acid residues dehydroalanine and dehydrobutyrine and five thio ether bridges. Since these structures are posttranslationally formed from Ser, Thr, and Cys residues, it is feasible to study their role in nisin function and biosynthesis by protein engineering. Here we report the development of an expression system for mutated nisin Z (nisZ) genes, using nisin A producing L. lactis as a host. Replacement by site-directed mutagenesis of the Ser-5 codon in nisZ by a Thr codon, led to a mutant with a dehydrobutyrine instead of a dehydroalanine residue at position 5, as shown by NMR. Its antimicrobial activity was 2-10-fold lower relative to wild-type nisin Z, depending on the indicator strain used. In another mutagenesis study a double mutation was introduced in the nisZ gene by replacing the codons for Met-17 and Gly-18 by codons for Gln and Thr, respectively, as in the third lanthionine ring of the related antimicrobial peptide subtilin from Bacillus subtilis. This resulted in the simultaneous production of two mutant species, one containing a Thr residue and the other containing a dehydrobutyrine residue at position 18, both having different bacteriocidal properties. PMID- 1447186 TI - Complexation with heparin prevents adhesion between fibrin-coated surfaces. AB - Heparin, in Langmuirian fashion, binds stoichiometrically with high affinity, Kd approximately 100 nM, to both fibrinogen and fibrin adsorbed as monomolecular films to lecithin-coated, microscopic, polystyrene-divinylbenzene beads. Complex formation inhibits aggregation of fibrin-coated beads, and it also results in dissociation of preformed aggregates of fibrin-coated beads. These phenomena are not caused by desorption of fibrin(ogen), indirect inhibition of thrombin activity, or mere electrostatic repulsion of charged particles. Instead, these data are consistent with the proposal that the complexed heparin interferes directly with dimer formation between fibrin molecules adsorbed to colliding beads. We describe these phenomena and their application to the development of sensitive analytical methods for quantitating heparin. Based on these observations, we also propose a role for endogenous heparin in the physiologic regulation of fibrin-mediated adhesion of surfaces. PMID- 1447187 TI - Interleukin-1 alpha mediates an alternative pathway for the antiproliferative action of poly(I.C) on human endothelial cells. AB - The antiproliferative effect of double-stranded RNA (dsRNA) on human tumor and normal cells has been well established. However, the genes involved in the dsRNA induced antiproliferative response and the molecular mechanisms by which this occurs remain less well defined. We have studied the ability of synthetic dsRNA, polyinosinic:polycytidylic acid (poly(I.C)) to modify human umbilical vein endothelial cell (HUVEC) growth and report that poly(I.C) induces a dose dependent inhibition of HUVEC proliferation in vitro. In addition, the mRNA levels for the cytokines interleukin-1 alpha (IL-1 alpha) and interferon-beta 1 are induced in poly(I.C)-treated cells. Moreover, the growth inhibitory effects of poly(I.C) are relieved when cells are grown in the presence of an IL-1 alpha antisense oligonucleotide to the human IL-1 alpha transcript. Thus, the effects of poly(I.C) appear to be mediated, in part, through the function of IL-1 alpha, suggesting an alternative pathway for dsRNA-mediated inhibition of human endothelial cell growth. PMID- 1447188 TI - Poly-N-acetyllactosaminyl O-glycans attached to leukosialin. The presence of sialyl Le(x) structures in O-glycans. AB - Poly-N-acetyllactosamine extension has been found in O-glycans in addition to N glycans and glycosphingolipids. Attempts were made in HL-60 and K562 cells to determine the amount of poly-N-acetyllactosaminyl O-glycans in the major sialoglycoprotein, leukosialin. Leukosialin was immunoprecipitated from [3H]glucosamine-labeled HL-60 and K562 cells. Glycopeptides were prepared by Pronase digestion, and O-glycan-containing glycopeptides were isolated by affinity chromatography using Jacalin-agarose. The glycopeptides bound to Jacalin agarose and those unbound were treated with alkaline borohydride, and the released O-glycans were fractionated by Bio-Gel P-4 filtration. Sequential glycosidase digestion of the O-glycans, with or without pretreatment by fucosidase or neuraminidase, revealed the following conclusions. 1) Leukosialin from HL-60 cells contains about 1-2 poly-N-acetyllactosaminyl O-glycan chains/molecule. 2) About 50% of these poly-N-acetyllactosaminyl O-glycans contain sialyl Le(x) termini, NeuNAc alpha 2-->3Gal beta 1-->4 (Fuc alpha 1- >3)GlcNAc beta 1-->R. The amount of sialyl Le(x) structure in leukosialin is roughly equivalent to that on cell surfaces of HL-60 cells. 3) Leukosialin from K562 cells, on the other hand, contains no detectable amount of poly-N acetyllactosaminyl O-glycans. 4) The presence of poly-N-acetyllactosamine in O glycans is dependent on the core 2 beta 1,6-N-acetylglucosaminyl transferase. 5) Jacalin-agarose binds to sialylated small oligosaccharides such as NeuNAc alpha 2 ->3Gal beta 1-->3(NeuNAc alpha 2-->6) GalNAc but not the hexasaccharide NeuNAc alpha 2-->3Gal beta 1-->3(NeuNAc alpha 2-->3Gal beta 1-->4GlcNAc beta 1-->6) GalNAc. These results indicate that the formation of polylactosaminyl O-glycans and sialyl Le(x) structure in O-glycans is dependent on the core 2 formation. PMID- 1447189 TI - Purification and cloning of a novel serine protease, RNK-Met-1, from the granules of a rat natural killer cell leukemia. AB - We have purified a 30-kDa serine protease (designated RNK-Met-1) from the granules of the rat large granular lymphocyte leukemia cell line (RNK-16) that hydrolytically cleaves model peptide substrates after methionine, leucine, and norleucine (Met-ase activity). Utilizing molecular sieve chromatography, heparin agarose, chromatography, and reverse-phase high pressure liquid chromatography, RNK-Met-1 was purified to homogeneity and 25 NH2-terminal amino acids were sequenced. By using the polymerase chain reaction, oligonucleotide primers derived from amino acids at position 14-25 and from a downstream active site conserved in other serine protease genes were used to generate a 534-base pair cDNA clone encoding a novel serine protease from RNK-16 mRNA. This cDNA clone was used to isolate a full-length 867-base pair RNK-Met-1 cDNA from an RNK-16 lambda gt11 library. The open reading frame predicts a mature protein of 238 amino acids with two potential sites for N-linked glycosylation. The cDNA also encodes a leader peptide of at least 20 amino acids. The characteristic Ile-Ile-Gly-Gly amino acids of the NH2 terminus and the His, Asp, and Ser residues that form the catalytic triad of serine proteases were both conserved. The amino acid sequence has less than 45% identity with any other member of the serine protease family, indicating that RNK-Met-1 is distinct and may itself represent a new subfamily of serine proteases. Northern blot analysis of total cellular RNA detected a single 0.9-kilobase mRNA in the in vitro and in vivo variants of RNK-16 and in spleen derived plastic-adherent rat lymphokine-activated killer cells. RNK-Met-1 mRNA was not detectable in freshly isolated rat splenocytes, thymocytes, brain, colon, and liver or activated nonadherent rat splenocytes and thymocytes. These data indicate that RNK-Met-1 is a serine protease with unique activity that is expressed in the granules of large granular lymphocytes. PMID- 1447190 TI - Two alternative structures can be formed by IHF protein binding to the plasmid R6K gamma origin. AB - Escherichia coli integration host factor (IHF) contributes to the regulation of R6K plasmid copy number by counteracting the inhibitory activity of the plasmid encoded replication protein pi. Two IHF-binding sites (ihf1 and ihf2) flank seven iterons in the origin which bind pi protein. As previously shown by electron microscopy, IHF can compact a large segment of the R6K gamma origin DNA, encompassing site ihf1, an AT-rich domain containing ihf1, and some of the seven iterons located downstream of ihf1. We termed this phenomenon IHF-mediated DNA folding. This folding requires a high IHF concentration, and the region of the origin (replication enhancer) located to the left of the AT-rich domain. However, site ihf2 is not necessary in forming the folded structure. As reported here, IHF binding to ihf2 can be detected in gel mobility shift assays only if the leftmost enhancer region is absent. Sites ihf1 and ihf2 each contain two consensus IHF sequences. Site-directed mutagenesis was performed to determine which sequences are recognized by IHF protein and which sites are involved in forming the various gamma origin-IHF complexes. Finally, we define the boundaries of protection from DNaseI digestion when IHF is bound to ihf2. We propose a model in which IHF protein bound to ihf1, in the absence of the enhancer region, facilitates IHF binding to ihf2. PMID- 1447191 TI - The transmembrane and flanking sequences of beta 1,2-N acetylglucosaminyltransferase I specify medial-Golgi localization. AB - UDP-GlcNAc:alpha 3-D-mannoside beta 1,2-N-acetylglucosaminyltransferase I (GnTI) is an N(in)/C(out) (type II) membrane protein, localized in the medial-Golgi, that initiates the conversion of high mannose N-glycans to complex N-glycans. Anti-rabbit GnTI antibodies were generated using a purified, enzymatically active, bacterial recombinant fusion protein as immunogen. Rabbit GnTI was effectively retained in the Golgi complex of transfected COS-1 cells and murine L cells, as assessed by indirect immunofluorescence using the species-specific anti GnTI antibodies; no surface expression of rabbit GnTI could be detected in the transfected cells. Rabbit GnTI, stably expressed in murine L cells, was localized by immunoperoxidase electron microscopy to the medial-cisternae of the Golgi stack. The role of the transmembrane domain of GnTI in Golgi localization was examined by generation of a hybrid construct containing the amino-terminal 31 amino acids of GnTI, corresponding to the 25-residue transmembrane (signal/anchor) domain and flanking hydrophilic sequences, fused with ovalbumin; this ovalbumin/GnTI hybrid molecule was retained in the Golgi complex of transfected COS cells and stably transfected murine L cells. No surface expression of ovalbumin/GnTI was detected. In contrast, ovalbumin fused to the equivalent domains of the human transferrin receptor, a type II cell-surface protein, was efficiently expressed on the cell surface of transfected cells. The ovalbumin/GnTI hybrid molecules in the transfected L cells were N-glycosylated, indicating an N(in)/C(out) membrane orientation, and were localized by immunoperoxidase electron microscopy to one or two cisternae of the medial-Golgi (90% of stained Golgi profiles showed medial-cisternae staining). These results show that a signal contained within the transmembrane domain and flanking residues of GnTI specifies medial-Golgi localization. PMID- 1447192 TI - Human and Giardia ADP-ribosylation factors (ARFs) complement ARF function in Saccharomyces cerevisiae. AB - ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro. ARFs are highly conserved, ubiquitously expressed in eukaryotic cells and appear to be involved in vesicular protein transport. The two yeast ARFs are > 60% identical to mammalian ARFs and are essential for cell viability (Stearns, T., Kahn, R. A., Botstein, D., and Hoyt, M. A. (1990) Mol. Cell. Biol. 10, 6690-6699). Although the two yeast ARF proteins are 96% identical in amino acid sequence, the yeast ARF1 gene is constitutively expressed, whereas the ARF2 gene is repressed by glucose. Human ARF5 and ARF6 and a Giardia ARF differ substantially in size and amino acid identity from other mammalian and eukaryotic ARFs but will, as befits their designation, activate cholera toxin. Expression of human ARF5, ARF6, or Giardia ARF cDNA rescued the lethal yeast ARF double mutant (arf1, arf2). Strains rescued by human ARF5, ARF6, or Giardia ARF grew much more slowly than wild-type yeast or strains rescued with yeast ARF1. We infer from the impaired growth of these rescued strains that the homologous ARFs may have specific targeting information that does not interact effectively or efficiently with the yeast protein membrane trafficking system. PMID- 1447193 TI - Purification and characterization of two forms of human transcription factor IIIC. AB - We showed previously that HeLa cell nuclear extracts contain two forms of transcription factor IIIC (TFIIIC) that formed chromatographically distinct TFIIIC-promoter complexes (Hoeffler, W. K., Kovelman, R., and Roeder, R. G. (1988) Cell 53, 907-920). One of these forms, the upper-band form, correlated with TFIIIC transcriptional activity, whereas the lower-band form bound to the VA1 promoter but supported little or no transcriptional activity. Using both transcription and DNA-binding assays, we have now purified both the upper-band form and the lower-band form of TFIIIC to near-homogeneity. The upper-band form is composed of five polypeptides with estimated sizes of 220, 110, 102, 90, and 63 kDa. The largest of these polypeptides can be cross-linked to the VA1 promoter. The lower-band form has a polypeptide structure similar to that of the upper-band form except for the absence or modification of the 110-kDa subunit. Direct assays show that the lower-band form is indeed transcriptionally inactive at all stages of purification, even when assayed with an unfractionated, heat treated nuclear extract as a complementation system. This inactivity does not result from altered DNA-binding properties; instead, we suggest that the alteration of one of the subunits of TFIIIC renders it unable to interact productively with a downstream component of the transcription complex. PMID- 1447194 TI - Iron regulates the activity of the iron-responsive element binding protein without changing its rate of synthesis or degradation. AB - The iron-responsive element binding protein (IRE-BP) interacts with specific sequence/structure motifs (iron-responsive elements) within the mRNAs encoding ferritin and the transferrin receptor and thereby post-transcriptionally regulates the expression of these two proteins involved in cellular iron homeostasis. The activity of the IRE-BP is itself regulated by iron such that when cells are treated with an iron source, the RNA binding activity is decreased. The expression of recombinant human IRE-BP in murine cells has been examined as have the expressions of the endogenous IRE-BP of both human and rabbit cells. In all cases, iron down-modulated the RNA binding activity of the IRE-BP, but in no instance was this decrease in activity accompanied by a decrease in the level of the protein as judged by quantitative Western blots. Moreover, the rate of synthesis of the IRE-BP and its rate of degradation have been found to be unaltered by iron manipulation of cells in culture. Consistent with IRE-BP regulation occurring post-translationally, the iron regulation of its activity was found to be unaffected by cycloheximide. These data are discussed in terms of a model of IRE-BP regulation involving the modification of the protein's iron-sulfur center. PMID- 1447195 TI - Reactions at the polymerase active site that contribute to the fidelity of Escherichia coli DNA polymerase I (Klenow fragment). AB - In order to study the structural principles governing DNA polymerase fidelity we have measured the rates of insertion of incorrect nucleotides and the rates of extension from the resulting mismatched base pairs, catalyzed by the Klenow fragment of DNA polymerase I. Using a combination of semi-quantitative and qualitative approaches, we have studied each of the 12 possible mismatches in a variety of sequence contexts. The results indicate that Klenow fragment discriminates between mismatches largely on the basis of the identity of the mismatch, with the surrounding sequence context playing a significant, but secondary, role. For purine-pyrimidine and pyrimidine-pyrimidine mispairs, the relative ease of mismatch synthesis and extension can be rationalized using a simple geometrical model, with the important criterion being the extent to which the mismatched base pair can conform to normal DNA geometry. Essentially similar conclusions have been reached in studies of other polymerases, suggesting that this aspect of mispair geometry is sensed and responded to in a similar way by all polymerases. Purine-purine mismatches form a less cohesive class, showing more variable behavior from mispair to mispair, and a greater apparent susceptibility to sequence context effects. Comparison of our data with studies of other polymerases also suggests that different polymerases respond to purine purine mismatches in distinct and characteristic ways. An extensive analysis of each of the four purine-purine mispairs in approximately 100 different sequence contexts suggests that the reaction is influenced both by the local DNA structure and by the ability of the mismatched terminus to undergo slippage. PMID- 1447196 TI - Cytochrome b560 (QPs1) of mitochondrial succinate-ubiquinone reductase. Immunochemistry, cloning, and nucleotide sequencing. AB - Mitochondrial succinate-ubiquinone reductase is composed of two parts, a water soluble succinate dehydrogenase and a two-polypeptide membrane-anchoring protein fraction (QPs). The larger polypeptide of QPs is believed to be associated with cytochrome b560 (QPs1). The structure of QPs1 was studied by immunochemistry and molecular cloning and sequencing. Antibodies against QPs1 were raised in rabbits, purified, and characterized by enzyme-linked immunosorbent assay and Western blotting. The purified antibodies inhibited 75% of the reconstitutive activity of QPs and reacted with both submitochondrial particles (SMP) and mitoplasts. The binding of these antibodies to SMP was greatly increased when succinate dehydrogenase was removed from SMP by alkaline treatment, indicating that QPs1 is a transmembranous protein and that some of its specific epitopes are covered by succinate dehydrogenase. Anti-QPs1 antibodies were used to screen one cDNA clone encoding QPs1 from a bovine heart cDNA lambda gt11 expression library. The cDNA insert is 946 base pairs with an open reading frame of 396 base pairs that encodes for 132 amino acid residues. The molecular weight of QPs1, calculated from the deduced amino acid sequence, is 14,320. Although the apparent molecular weight of QPs1, estimated by high resolution SDS-polyacrylamide gel electrophoresis, is approximately 11,000, the existence of a presequence was ruled out by mass spectrometric analysis of protein fragments. QPs1 is a very hydrophobic protein. Three probable membrane-spanning segments were revealed by a hydropathy plot of the sequence. QPs1 has a higher sequence similarity to the sdhC peptide of Escherichia coli than to the sdhC peptide (cytochrome b558) of Bacillus subtilis. Like the bacterial proteins, QPs1 has 2 conserved histidines at positions 34 and 90. The conserved nature and similar location of these 2 histidines, on the matrix-side surface of the membrane, suggest that they are involved in heme ligation of cytochrome b560. PMID- 1447197 TI - Membrane insertion of the mannitol permease of Escherichia coli occurs under conditions of impaired SecA function. AB - The membrane insertion of the mannitol permease (MtlA protein) of Escherichia coli, a polytopic cytoplasmic membrane protein possessing an uncleaved amphiphilic signal sequence, was studied using a cell-free protein synthesis system. The MtlA protein synthesized in the presence of inside-out cytoplasmic membrane vesicles was shown to insert into the membranes based on the following criteria: (a) co-sedimentation of the majority of the MtlA protein with the vesicles; (b) selective extraction of the membrane-associated MtlA by doxycholate but not by urea treatment; and (c) protease resistance of a defined MtlA fragment observed exclusively in the presence of membranes. Post-translational addition of membrane vesicles allowed membrane association of MtlA but did not allow efficient integration. In cell-free systems having reduced levels of the export factors SecA and SecB and exhibiting defective translocation of preOmpA and preLamB, insertion of the in vitro synthesized MtlA apparently occurred normally. In contrast, when membranes from the secY24ts mutant or trypsin-treated membranes were used, insertion of MtlA was reduced. In vivo experiments monitoring the permease activity of MtlA in the secA and secY mutants supported the conclusions of the in vitro results. Thus, the insertion of MtlA is essentially SecA- and SecB-independent but may be dependent on SecY and/or an as yet unidentified membrane protein. The requirements for the insertion of the mannitol permease are therefore clearly different from those for the translocation of most proteins having a cleavable hydrophobic signal sequence. PMID- 1447198 TI - The structural organization of type IV collagen. Identification of three NC1 populations in the glomerular basement membrane. AB - Type IV collagen, which has long been assumed to contain two alpha 1(IV) and one alpha 2(IV) chains, also contains alpha 3(IV), alpha 4(IV), and alpha 5(IV) chains. Stoichiometry of collagenous alpha(IV) chains differs among tissues, suggesting the existence of subclasses of type IV collagen, each with a unique chain composition. This study seeks to define, by characterization of subunit compositions of NC1 domain populations, the structural organization of type IV collagen from bovine glomerular basement membrane. NC1 hexamers from type IV collagen were separated on two affinity chromatography columns, one containing monoclonal antibodies to the alpha 3 chain, and another, to the alpha 1 chain. SDS-polyacrylamide gel electrophoresis, immunoblotting, reversed phase high performance liquid chromatography, and enzyme-linked immunosorbent assay identified three NC1 hexamer populations: 1) a hexamer composed of (alpha 1)2 and (alpha 2)2 homodimers; 2) a hexamer composed of (alpha 3)2 and (alpha 4)2 homodimers; 3) a hexamer containing all four alpha chains connected in heterodimers, alpha 1-alpha 3 and alpha 2-alpha 4. Results suggest that there are two distinct type IV collagen molecules, one composed of alpha 1(IV) and alpha 2(IV) chains and another composed of alpha 3(IV) and alpha 4(IV) chains. Furthermore, polymerization occurs between molecules with the same chain composition and between molecules with different chain composition. Moreover, crosslinking between different alpha chains is restricted, thus limiting the number of possible macromolecular structures. PMID- 1447199 TI - Six amino acids determine the sequence-specific DNA binding and replication specificity of the initiator proteins of the pT181 family. AB - The replication of pT181 and related plasmids of Staphylococcus aureus proceeds by a rolling circle mechanisms. The initiator proteins encoded by the plasmids of the pT181 family have sequence-specific DNA binding and topoisomerase activities. These proteins nick one strand of the DNA at the origin of replication. The free 3'-hydroxyl end at the nick is then used as a primer for the replication of the leading strand of the DNA. Although these initiator proteins are highly homologous, they show specificity in DNA binding and replication for their cognate DNAs. In this study, we have generated hybrid initiator proteins and studied their various biochemical activities in vitro. Our results show that 6 amino acids are sufficient to determine the DNA binding and replication specificities of such initiator proteins. PMID- 1447200 TI - Preferential interaction of albumin-binding proteins, gp30 and gp18, with conformationally modified albumins. Presence in many cells and tissues with a possible role in catabolism. AB - Albumin binding to the endothelial surface apparently initiates its transcytosis via plasmalemmal vesicles and also increases capillary permselectivity. Several albumin-binding proteins, which, we call gp60, gp30, and gp18, have been identified; however, their functional relationship to each other is unclear. In this study, we show that gp30 and gp18 are both variably expressed by cultured rat fibroblasts, smooth muscle cells, and endothelial cells and are present in all tissues examined (heart, lung, skeletal muscle, diaphragm, duodenum, kidney, fat, brain, adrenal, pancreas, and liver). The binding of albumin-gold complexes (A-Au) to gp30 and gp18 was compared with that of native and modified albumins. Monomeric native bovine serum albumin (BSA) interacted much less avidly than A-Au and BSA that was chemically modified by formaldehyde (Fm-BSA) or maleic anhydride (Mal-BSA). Mal-BSA and A-Au have similar affinity constants for gp30 and gp18 (KD approximately 3-7 micrograms/ml (50-100 nM)), which is 1000-fold greater than BSA. These interactions were Ca(2+)-independent but sensitive to pH (< 6.0) and high salt concentrations (> or = 1.0 M). Comparative biochemical characterization provided evidence of conformational changes for Mal-BSA, Fm-BSA, and A-Au. Anti native BSA serum recognizes BSA much more avidly than modified BSA. Mal-BSA, Fm BSA, and A-Au are much more sensitive to trypsin digestion than BSA. Cellular processing was also examined. A-Au and Mal-BSA bound at the endothelial cell surface were degraded, whereas BSA was not. Our results indicate that: (i) gp30 and gp18, unlike gp60, are expressed in all tissues tested regardless of the type of endothelia lining the microvasculature and the local mechanism of transendothelial albumin transport; (ii) BSA conformationally modified by either surface adsorption or chemical means not only interacts more avidly with gp30 and gp18 than native albumin but also is preferentially degraded by the cells; (iii) A-Au and native albumin are not equivalent probes for detecting albumin interaction sites; and (iv) gp30 and gp18 exhibit binding behavior resembling scavenger receptors. The possible roles of gp30 and gp18 in albumin binding, transcytosis, endocytosis, and even protein catabolism are discussed. PMID- 1447201 TI - The helix-loop-helix/leucine repeat transcription factor USF can be functionally regulated in a redox-dependent manner. AB - We showed previously that the DNA-binding capacity of the helix-loop helix/leucine repeat transcription factor USF43 is lowered dramatically under nonreducing conditions. This report defines the molecular basis of this effect by showing (i) that the only two USF43 cysteine residues, both present within the helix-loop-helix protein-protein interface domain, are required for this regulation, (ii) that the sulfhydryl groups of these cysteine residues are the actual targets of this regulation, (iii) that oxidation of these groups results in both intra- and intermolecular nonrandom covalent links, (iv) that this redox modulation of USF43 DNA-binding potential can translate in vitro into a specific modulation of its ability to activate transcription from a USF-responsive promoter. The implications of these modulations of USF43 function in response to redox changes are discussed with regard to the apparent paradox of USF strong activation potential and its ubiquitous distribution in all cell types tested. PMID- 1447202 TI - Functional expression of bovine 17 alpha-hydroxylase in COS 1 cells is dependent upon the presence of an amino-terminal signal anchor sequence. AB - Microsomal forms of eukaryotic cytochrome P450 proteins are integral membrane proteins of the endoplasmic reticulum (ER) membrane which are targeted to the ER via the signal recognition particle pathway. A hydrophobic amino terminus serves as a combined signal sequence and major membrane anchor (signal-anchor sequence) for the microsomal P450s. We have examined the insertion of bovine 17 alpha hydroxylase (P45017 alpha) into the ER of COS 1 cells in order to evaluate the role of membrane insertion of the amino-terminal signal-anchor of microsomal P450s as a functional determinant for these enzymes. Previously, we have shown that deletion of the hydrophobic amino terminus from P45017 alpha reduced membrane targeting and insertion by 5-fold compared with the wild-type protein, abolished enzymatic activity, and resulted in an aberrant CO difference spectrum. In the present study we have replaced the amino terminus of P45017 alpha with two heterologous signal-anchor sequences, one that is similar and one that is very different from the P45017 alpha sequence. The chimeric proteins were expressed in COS 1 cells. Immunoblot analysis of isolated microsomal membranes show that the heterologous signal-anchor sequences functioned to target the P45017 alpha protein to the ER. Enzymatic assays in intact COS 1 cells indicate that both the chimeric proteins are efficient 17 alpha-hydroxylase enzymes. The amino terminus of P45017 alpha was also replaced with a sequence that is not a signal-anchor, and the expressed protein was neither targeted to the ER nor was functional in COS 1 cells. In conclusion, both the structure and catalytic activity of P45017 alpha in COS 1 cells is dependent upon an amino-terminal sequence that functions as a signal-anchor sequence and not upon the precise sequence of the amino terminus. PMID- 1447203 TI - 2,3,7,8-Tetrachlorodibenzo-p-dioxin-dependent regulation of transforming growth factors-alpha and -beta 2 expression in a human keratinocyte cell line involves both transcriptional and post-transcriptional control. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent modulator of epithelial cell growth and differentiation, has been shown to induce transforming growth factor (TGF)-alpha in cultures of human keratinocytes and in the human keratinocyte cell line, SCC-12F. In this report, we investigated the mechanisms by which TCDD alters TGF-alpha expression. In addition, we studied the actions of TCDD on TGF beta 1 and TGF-beta 2 expression. Treatment of SCC-12F cells with TCDD resulted in an increase in TGF-alpha and a reduction in TGF-beta 2 mRNA levels while mRNA levels for TGF-beta 1 were unchanged. Changes in TGF-alpha and TGF-beta 2 expression were maximal by 24 h. No change in the rate of transcription of TGF alpha was detected following treatment with TCDD as determined by nuclear run-off analysis. TCDD treatment resulted in a stabilization of TGF-alpha mRNA as judged by an approximately 2-fold higher level of TGF-alpha mRNA in treated versus control cells in the presence of actinomycin D. In contrast to TGF-alpha, the rate of transcription of TGF-beta 2 was significantly reduced following TCDD treatment. These findings demonstrate that the induction of TGF-alpha expression in SCC-12F cells by TCDD occurs post-transcriptionally, primarily by mRNA stabilization, while TGF-beta 2 expression is reduced due to a decrease in the rate of TGF-beta 2 gene transcription. PMID- 1447204 TI - Complexity of ethanolamine phosphate addition in the biosynthesis of glycosylphosphatidylinositol anchors in mammalian cells. AB - Biosynthetic intermediates for the mammalian glycosylphosphatidylinositol (GPI) anchor have been described. The earliest GPI anchor precursor is N acetylglucosaminylphosphatidylinositol, which is deacetylated to give glucosaminylphosphatidylinositol. This is followed by fatty acylation of the inositol ring, sequential addition of mannose residues donated by dolichyl mannosyl phosphate, and finally addition of ethanolamine phosphate. Here, we show that the final steps of GPI anchor biosynthesis are more complex than we have previously reported. Six distinct GPI anchor precursors were found to contain at least 1 ethanolamine phosphate residue. The headgroups of these glycolipids were purified and analyzed by a combination of Bio-Gel P4 chromatography and high resolution thin-layer chromatography. The sizes of neutral glycans were determined following HF dephosphorylation. The position of the ethanolamine phosphate residue was inferred from results of alpha-mannosidase treatment. Finally, the number of negative charges on the headgroups were determined by Mono Q chromatography. Our results show that the addition of ethanolamine phosphate is controlled by at least two different genes. Thus, the class F mutant, though unable to add ethanolamine phosphate to the third mannose residue, does incorporate ethanolamine phosphate into the first and second mannose residues. Only the wild type cells are capable of incorporating ethanolamine phosphate into the third mannose residue. Furthermore, the GPI core contains up to 3 ethanolamine phosphate residues. These results should facilitate the elucidation of the biochemical defects in paroxysmal nocturnal hemoglobinuria. PMID- 1447205 TI - P-domains as shuffled cysteine-rich modules in integumentary mucin C.1 (FIM-C.1) from Xenopus laevis. Polydispersity and genetic polymorphism. AB - A new frog integumentary mucin (FIM-C.1) has been discovered by molecular cloning. This mucin contains at least six typical P-domains as cysteine-rich modules. Shuffled P-domains have previously been detected in FIM-A.1, and they also form the basis of various P-domain peptides, which presumably have growth modulating activities. Furthermore, FIM-C.1 contains at least three threonine rich clusters, which consist of semi-repetitive cassettes. Various polydisperse transcripts have been characterized. They originate from two genes only and differ by deletions/insertions that are congruent with the semi-repetitive cassettes. Thus, polydispersities are probably generated by alternative splicing. Southern analysis revealed genetic polymorphism between different individuals. Furthermore, a specific antiserum was generated against a synthetic peptide deduced from the COOH-terminal end of FIM-C.1 and used for Western analysis. PMID- 1447206 TI - Two related genes encoding extremely hydrophobic proteins suppress a lethal mutation in the yeast mitochondrial processing enhancing protein. AB - The processing enhancing protein of mitochondria (PEP) is an essential component that has been shown to participate in proteolytic removal of NH2-terminal signal peptides from precursor proteins imported into the mitochondrial matrix. Using a yeast strain bearing a PEP mutation that renders it temperature-sensitive, an approach of genetic suppression was taken in order to identify additional components that could be involved with protein import: high copy plasmids comprising a yeast genomic library were tested for ability to suppress the 37 degrees C growth defect. Two plasmids were isolated, pSMF1 and pSMF2, which suppressed the growth defect nearly as well as the cloned PEP gene itself. Sequence analysis of the rescuing genes predicted extremely hydrophobic proteins with sizes of 63 and 60 kDa, respectively. Remarkably, the predicted SMF1 and SMF2 products are 49% identical to each other overall. To test the requirement for SMF1 and SMF2, the chromosomal genes were disrupted. Individual disruption was without effect, but cells in which both genes were disrupted grew poorly. When mitochondria were prepared from the double disruption strain grown in a nonfermentable carbon source, they were morphologically normal but defective for translocation of radiolabeled precursor proteins. SMF1 protein was provisionally localized to the mitochondrial membranes using epitope tagging. We suggest that SMF1 and SMF2 are mitochondrial membrane proteins that influence PEP-dependent protein import, possibly at the step of protein translocation. PMID- 1447207 TI - Inactivation of ribonuclease inhibitor by thiol-disulfide exchange. AB - Porcine ribonuclease inhibitor (RI) contains 30 1/2-cystinyl residues, all of which occur in the reduced form. Reaction of the native protein with 5,5' dithiobis (2-nitrobenzoic acid) resulted in the release of 30 mol of the product 5-mercapto-2-nitrobenzoate, and the loss of the RNase inhibitory activity. A linear relationship between the degree of modification and inactivation was observed. The rate of modification was greatly increased in the presence of 6 M guanidinium HCl. Reaction with substoichiometric amounts of 5,5'-dithiobis(2 nitrobenzoic acid) was found to yield a mixture of fully reduced active molecules, and fully oxidized inactive ones, but no partially oxidized forms were detected. This suggests that an "all-or-none" type of modification and inactivation took place. All 1/2-cystinyl residues in the inactive, monomeric inhibitor had formed disulfide bridges, judged by the absence of either free thiol groups or mixed disulfides with 5-mercapto-2-nitrobenzoate. This fully disulfide-cross-linked molecule had an open conformation compared to the native one, as shown by gel filtration and limited proteolysis. Reaction of phenylarsinoxide with vicinal dithiols yields products that are much more stable than those with monothiols. Titration of RI with this reagent yielded complete inactivation at a reagent/thiol ratio of 0.5. Taken together, these observations suggest that the thiol groups in RI have a diminished reactivity due to three dimensional constraints. After the initial modification of a small number of thiol groups, a conformational change occurs which causes an increase in reactivity of the remaining thiols. The thiol groups are situated close enough together to permit the formation of 15 disulfide bridges in the inactive molecule. PMID- 1447208 TI - Mutational analysis of the Escherichia coli phosphate-specific transport system, a member of the traffic ATPase (or ABC) family of membrane transporters. A role for proline residues in transmembrane helices. AB - The Escherichia coli Pst system is a periplasmic phosphate permease. A mutational analysis of the requirement for function of specific charged residues or proline residues in the two hydrophobic subunits (PstC and PstA) has been carried out. No residues, among 19 charged residues altered, were found to be essential for phosphate uptake, although some alterations resulted in partial effects. Evidence was obtained that the 3 residues, R220 in the PstA protein and R237 and E241 in the PstC protein, previously shown to be required for phosphate transport (Cox, G. B., Webb, D., Godovac-Zimmermann, J., and Rosenberg, H. (1988) J. Bacteriol. 170, 2283-2286; Cox, G. B., Webb, D., and Rosenberg, H. (1989) J. Bacteriol. 171, 1531-1534), interact with each other. A feature of the proposed structures of the PstA and PstC proteins was 2 pairs of proline residues in putative transmembrane helices 3 and 4. While individual substitutions of these proline residues by leucine resulted in loss of phosphate transport activity substitution by alanine only had partial effects. However, if the proline to alanine changes were paired then, depending on the particular subunit, markedly different effects were obtained. The double mutation in the PstA protein resulted in a permanently "closed" system, whereas the double mutation in the PstC protein resulted in a permanently "open" transport system. PMID- 1447209 TI - Characterization of the spectrum of alternative splicing of alpha 1 (XIII) collagen transcripts in HT-1080 cells and calvarial tissue resulted in identification of two previously unidentified alternatively spliced sequences, one previously unidentified exon, and nine new mRNA variants. AB - Amplification of a COL1-encoding region of alpha 1 (XIII) collagen transcripts of HT-1080 cell RNA suggested that exon 3 of the alpha 1 (XIII) collagen gene, which was previously deduced to be of 35 base pairs (bp) may consist of a constitutive 8-bp exon and an alternatively spliced 27-bp exon, termed here exons 3A and 3B, respectively. Furthermore, a previously unidentified alternatively spliced Gly Xaa-Yaa-encoding exon designated as 4B was found between the sequences encoded by exons 4, redesignated here as 4A and 5. Six of the 16 potential combinations of the four consecutive alternatively spliced exons 3B, 4A, 4B, and 5 were found to exist in mRNAs, and as a result, the length of the COL1 domain may vary between 57 and 104 amino acid residues. Most of the NC2 domain is encoded by the alternatively spliced exons 12 and 13. Where previous analysis of cDNAs indicated that mRNA variants exist that contain either exon 12 or 13 sequences, amplification studies indicated here that there are also variants that lack both exons 12 and 13 but none that contain both exons simultaneously. Thus, the predicted length of this domain is either 12, 31, or 34 residues. Analyses covering both the COL1 and NC2 domains demonstrate that at least 12 mRNA species exist through the alternations of exons 3B-5, 12, and 13. PMID- 1447210 TI - Patterns of expression of the six alternatively spliced exons affecting the structures of the COL1 and NC2 domains of the alpha 1(XIII) collagen chain in human tissues and cell lines. AB - Reverse transcription-polymerase chain reactions and RNA protection experiments were used to examine alternative splicing of the six exons 3B-5, 12, and 13 affecting the COL1 and NC2 domains of type XIII collagen in seven human tissues and four cell lines. Distinct differences in the proportions of the variant mRNAs were found. With respect to the COL1 domain, all studied samples contained mRNAs corresponding to the shortest COL1 variants of 57 and 66 residues, with the former variant being prominent in most samples. Most of the samples also contained notable amounts of mRNAs that corresponded to the longest COL1 variants, mainly those of 104 and 95 residues. Particularly the extent of inclusion of exon 12 and 13 sequences, encoding most of the NC2 domain, varied according to the type of tissue or cell analyzed. Bone, cartilage, and colon adenocarcinoma samples contained little or none of the mRNAs corresponding to the long NC2 variants, whereas in fibroblast, lung, muscle, and osteosarcoma cells, those mRNAs were the major variants. The relative proportions of the various combinations of exons 3B-5, 12, and 13 were evaluated in four of the RNA samples. Interestingly, each of these samples appeared to contain only one to three major combinations of the six exons, representing about 40% to nearly 100% of all variants. PMID- 1447211 TI - Isolation and characterization of the yeast gene encoding the MDH3 isozyme of malate dehydrogenase. AB - The MDH3 isozyme of Saccharomyces cerevisiae was purified from a haploid strain containing disruptions in genomic loci encoding the mitochondrial MDH1 and nonmitochondrial MDH2 isozymes. Partial amino acid sequence analysis of the purified enzyme was conducted and used to plan polymerase chain reaction techniques to clone the MDH3 gene. The isolated gene was found to encode a 343 residue polypeptide with a molecular weight of 37,200. The deduced amino acid sequence was closely related to those of MDH1 (50% residue identity) and of MDH2 (43% residue identity). The MDH3 sequence was found to contain a carboxyl terminal SKL tripeptide, characteristic of many peroxisomal enzymes, and immunochemical analysis was used to confirm organellar localization of the MDH3 isozyme. Levels of MDH3 were determined to be elevated in cells grown with acetate as a carbon source, and under these conditions, MDH3 contributed approximately 10% of the total cellular malate dehydrogenase activity. Disruption of the chromosomal MDH3 locus produced a reduction in cellular growth rates on acetate, consistent with the presumed function of this isozyme in the glyoxylate pathway of yeast. Combined disruption of MDH1, MDH2, and MDH3 loci in a haploid strain resulted in the absence of detectable cellular malate dehydrogenase activity. PMID- 1447212 TI - A comparison of the rates of reaction and function of UVRB in UVRABC- and UVRAB mediated anthramycin-N2-guanine-DNA repair. AB - The repair of anthramycin-DNA adducts by the UVR proteins in Escherichia coli follows two pathways: the adducts may be incised by the combined actions of UVRA, UVRB, and UVRC, or alternatively, the anthramycin may be removed by UVRA and UVRB in the absence of UVRC and with no DNA strand incision. To assess the competition between these two competing pathways, the rate of UVRABC-mediated excision repair of anthramycin-N2-guanine DNA adducts and the rate of UVRAB-mediated removal of the adduct were measured with single end-labeled DNAs under identical reaction conditions. UVR protein concentrations of 15 nM UVRA, 100 nM UVRB, and 10 nM UVRC protein were chosen to mimic in vivo concentrations. With these UVR protein concentrations and anthramycin-DNA concentrations of 1-2 nM the incision reaction and the release reactions are described by first-order kinetics. The rate of the UVRABC reaction, measured as the increase in incised fragments, was six to seven times faster than the rate of the UVRAB reaction, measured as the decrease in incised fragments. The UVRABC incision rate on anthramycin-modified linear DNA was four to five times the incision rate measured on the same DNA irradiated with ultraviolet light. We also investigated the role of the ATPase function of UVRB in UVRAB-mediated anthramycin removal. We found that a UVRB analogue with alanine at arginine 51, which retains near wild type ATPase activity, supported removal of anthramycin in the presence of UVRA, whereas a UVRB analogue with alanine at lysine 45, which abolishes the ATPase activity, did not. UVRB*, a specific proteolytic cleavage product of UVRB which retains the ATPase activity, did support removal of anthramycin in the presence of UVRA. PMID- 1447213 TI - Cell surface expression of the C3b/C4b receptor (CR1) protects Chinese hamster ovary cells from lysis by human complement. AB - The C3b/C4b receptor, also known as complement receptor type 1 (CR1, CD35), is a single chain glycoprotein consisting of 30 repeating homologous protein domains known as short consensus repeats (SCR) followed by transmembrane and cytoplasmic domains. A series of recombinant proteins derived from CR1 has been prepared and assessed for the capacity to inhibit complement lysis of the host Chinese hamster ovary (CHO) cells. The full-length recombinant CR1 inhibited human complement mediated CHO cell lysis, and the efficiency of inhibition was directly proportional to the number of receptors/cell. The SCR 15-18 of CR1, but not SCR 15-16, inhibited complement lysis of the host CHO cell, bound monomeric C3b (Kd,app = 6.5 x 10(-7) M), and dimeric C3b (Kd = 1.8 x 10(-8) M), and served as a cofactor in the proteolysis of C3b by factor I, confirming and extending the observations of Fearon and colleagues (Kalli, K. R., Hsu, P., Bartow, T. J., Ahearn, J. M., Matsumoto, A. K., Klickstein, L. B., and Fearon, D. T. (1991) J. Exp. Med. 174, 1451-1460). The SCR 1-4 of CR1, but not SCR 1-2, also inhibited complement lysis of the host CHO cell, indicating that more than two SCR are necessary and that four SCR are sufficient for optimal C4b binding to CR1. Thus, the structural requirements for C4b binding are analogous to those for C3b binding, namely, four SCR of CR1 form the binding sites for each of these proteins. CR1 has long been recognized to regulate extrinsic complement activation, that is, to bind to and promote the degradation of fluid phase C3b and of C3b attached to immune complex. These results demonstrate that CR1 is also an intrinsic regulator of complement activation in that, under appropriate conditions, CR1 inhibits complement-mediated lysis of the cell on which it is expressed. PMID- 1447214 TI - A role for the acidic trimer repeat region of transcription factor sigma 54 in setting the rate and temperature dependence of promoter melting in vivo. AB - sigma 54 is an atypical sigma factor involved in enhancer-dependent transcription in Escherichia coli. In vivo assays were developed for following the kinetics and thermodynamics of sigma 54-dependent melting of the glnAP2 promoter start site. These assays were applied to a series of three sigma 54 polymerases containing zero, one, and two copies of the highly acidic trimer repeat region. The results showed that at least one copy of this acid region is required for a complete melting transition at physiological temperature, but is not required for a low temperature melting transition. The rate of melting the promoter in vivo increased with number of copies of this region. Taken together with other observations, the experiments point to a role for the acid region in triggering conformational changes that lead to specific promoter melting. The acid region is required for these changes to occur fully at physiological temperature and influences the rate at which they occur. PMID- 1447215 TI - A third form of the G protein beta subunit. 1. Immunochemical identification and localization to cone photoreceptors. AB - Vertebrate retinal cones play a major role in both photopic vision and color perception. Although the molecular mechanism of visual excitation in the cone is not as well understood as in the rod, it is generally thought to involve a cone specific G protein (cone transducin) that couples the cone visual pigment to a cGMP phosphodiesterase. Like all other G proteins, cone transducin is most likely a heterotrimer consisting of G alpha, G beta, and G gamma subunits. A G alpha subunit of cone transducin has been localized to the outer segment of bovine cones, but its associated G beta and G gamma subunits are unknown. To identify the G beta subunit involved in the phototransduction process of cones, we have developed a panel of antipeptide antisera against the most diverse region of the amino acid sequences encoded by G beta 1, G beta 2, and G beta 3 cDNAs and used them to determine the distribution of the G beta isoforms in different retinal preparations. We found that the G beta 3 subunit is present in bovine retinal transducin and phosducin-T beta gamma complex preparations which were previously thought to contain only G beta 1. Analysis of its subcellular distribution indicated that G beta 3 is predominantly cytoplasmic. Immunocytochemical staining of bovine retinal sections with the anti-G beta 3 antiserum further revealed a specific localization of G beta 3 in cones but not in rods. In contrast, anti-G beta 1 antiserum stained only the rods. These results suggest that G beta 3 is the G beta subunit of cone transducin and confirms the proposition that rods and cones utilize distinct signaling proteins for phototransduction. PMID- 1447216 TI - Modulation of a Ca2+ signaling pathway by GM1 ganglioside in PC12 cells. AB - The effects of exogenous GM1 ganglioside on depolarization and ligand-induced Ca2+ signaling were investigated in PC12 cells. Cellular responses to K+ depolarization and bradykinin application in control and GM1-treated cells were examined with respect to: 1) changes in the intracellular Ca2+ concentration ([Ca2+]i) measured using fura-2 fluorescence in single cells, and 2) changes in Ca(2+)-dependent protein kinase activity as assayed by two-dimensional phosphopeptide analysis of the site-specific phosphorylation of tyrosine hydroxylase. Pretreatment of cells with GM1 (10 or 100 microM) enhanced K+ depolarization-stimulated increases in [Ca2+]i and in 32PO4 incorporation into tyrosine hydroxylase phosphopeptide T2, a Ca2+/calmodulin-dependent protein kinase II substrate. In contrast, GM1 treatment had no effect on the transient increases in [Ca2+]i evoked by bradykinin or on bradykinin-induced increases in the site-specific phosphorylation of tyrosine hydroxylase. The depolarization induced and GM1-enhanced increases in [Ca2+]i and T2 phosphorylation were prevented by removal of external Ca2+ or pretreatment with 1 microM nitrendipine, suggesting that these increases result from Ca2+ entry through dihydropyridine sensitive Ca2+ channels. The ability of exogenous gangliosides to potentiate increases in [Ca2+]i may underlie their diverse neuritogenic and neurotrophic actions in the nervous system. PMID- 1447217 TI - Structure and chromosomal localization of human arachidonate 12-lipoxygenase gene. AB - Arachidonate 12-lipoxygenase introduces a molecular oxygen into the C-12 position of arachidonic acid to produce 12(S)-hydroperoxy-5,8,10,14-eicosatetraenoic acid. With the aid of cDNA probes for the enzyme, we isolated overlapping lambda clones encompassing the human 12-lipoxygenase gene and flanking regions from a human genomic library. The gene consists of 14 exons with 13 introns and spans approximately 15 kilobases of DNA. All the exon-intron junctions conform to the GT/AG rule. Neither a typical TATA box nor a CAAT box was found in approximately 1-kb sequence of 5'-upstream region of the translation initiation site. However, this region contains several regulatory elements including four GC boxes, two CACCC boxes, three AP-2 binding sequences, and a glucocorticoid-responsive element. The major transcription initiation site was determined by primer extension analysis as an adenosine residue at 306 bases upstream from the translation initiation codon. The chromosomal localization of the human 12 lipoxygenase gene was examined by fluorescence in situ hybridization, and the gene was assigned to the sub-band p13.1 of chromosome 17. PMID- 1447218 TI - Stereoselective interaction with chiral phosphorothioates at the central DNA kink of the EcoRI endonuclease-GAATTC complex. AB - We have probed the contacts between EcoRI endonuclease and the central phosphate of its recognition site GAApTTC, using synthetic oligonucleotides containing single stereospecific Rp- or Sp-phosphorothioates (Ps). These substitutions produce subtle stereospecific effects on EcoRI endonuclease binding and cleavage. An Sp-Ps substitution in one strand of the DNA duplex improves binding free energy by -1.5 kcal/mol, whereas the Rp-Ps substitution has an unfavorable effect (+0.3 kcal/mol) on binding free energy. These effects derive principally from changes in the first order rate constants for dissociation of the enzyme-DNA complexes. The first order rate constants for strand scission are also affected, in that a strand containing Sp-Ps substitution is cleaved 2 to 3 times more rapidly than a strand containing a normal prochiral phosphate, whereas a strand containing Rp-Ps substitution is cleaved about 3 times slower than normal. As a result, single-strand substitutions produce pronounced asymmetry in the rates of cleavage of the two DNA strands, and this effect is exaggerated in an Rp,Sp heteroduplex. Ethylation-interference footprinting indicates that none of the Ps substitutions cause any major change in contacts between endonuclease and DNA phosphates. When an Sp-Ps localizes P = O in the DNA major groove, a hydrogen bonding interaction with the backbone amide-NH of Gly116 of the endonuclease is improved relative to that with a prochiral phosphate having intermediate P-O bond order and delocalized charge. PMID- 1447219 TI - An atomic model for protein-protein phosphoryl group transfer. AB - The high resolution crystal structures of two interacting proteins from the phosphoenolpyruvate:sugar phosphotransferase system, the histidine-containing phosphocarrier protein (HPr) and the IIA domain of glucose permease (IIA(Glc)) from Bacillus subtilis, provide the basis for modeling the transient binary complex formed during the phosphoryl group transfer. The complementarity of the interacting surfaces implies that no major conformational transition is required. The negatively charged phosphoryl group is buried in the interface, suggesting a key role for electrostatic interactions. It is proposed that the phosphoryl transfer is triggered by a switch between two salt bridges involving Arg-17 of the HPr. The first, prior to phosphoryl group transfer, is intramolecular, with the phosphorylated His-15. The second, during the transfer, is intermolecular, with 2 aspartate residues associated with the active site of IIA(Glc). Such alternating ion pairs may be mechanistically important in other protein-protein phosphotransfer reactions. PMID- 1447220 TI - Use of structure-directed DNA ligands to probe the binding of recA protein to narrow and wide grooves of DNA and on its ability to promote homologous pairing. AB - We have used circular dichroism and structure-directed drugs to identify the role of structural features, wide and narrow grooves in particular, required for the cooperative polymerization, recognition of homologous sequences, and the formation of joint molecules promoted by recA protein. The path of cooperative polymerization of recA protein was deduced by its ability to cause quantitative displacement of distamycin from the narrow groove of duplex DNA. By contrast, methyl green bound to the wide groove was retained by the nucleoprotein filaments comprised of recA protein-DNA. Further, the mode of binding of these ligands and recA protein to DNA was confirmed by DNaseI digestion. More importantly, the formation of joint molecules was prevented by distamycin in the narrow groove while methyl green in the wide groove had no adverse effect. Intriguingly, distamycin interfered with the production of coaggregates between nucleoprotein filaments of recA protein-M13 ssDNA and naked linear M13 duplex DNA, but not with linear phi X174 duplex DNA. Thus, these data, in conjunction with molecular modeling, suggest that the narrow grooves of duplex DNA provide the fundamental framework required for the cooperative polymerization of recA protein and alignment of homologous sequences. These findings and their significance are discussed in relation to models of homologous pairing between two intertwined DNA molecules. PMID- 1447221 TI - The crystal structure of the aldose reductase.NADPH binary complex. AB - Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the reduction of a broad range of aldehydes, including glucose. Since aldose reductase has been strongly implicated in the development of the chronic complications of diabetes mellitus, much effort has been devoted to understanding the structure and mechanism of this enzyme, and many aldose reductase inhibitors have been developed as potential drugs for the treatment of these complications. We describe here the 2.75 A crystal structure of recombinant human aldose reductase (Cys-298 to Ser mutant) complexed with NADPH. This mutant displays unusual kinetic behavior characterized by high Km/high Vmax substrate kinetics and reduced sensitivity to certain aldose reductase inhibitors. The crystal structure revealed that the enzyme is a beta/alpha-barrel with the coenzyme binding domain located at the carboxyl-terminal end of the parallel strands of the barrel. The enzyme undergoes a large conformational change upon binding NADPH which involves the reorientation of loop 7 to a position which appears to lock the coenzyme into place. NADPH is bound to aldose reductase in an unusual manner, more similar to FAD- rather than NAD(P)-dependent oxidoreductases. No disulfide bridges were observed in the crystal structure. PMID- 1447222 TI - AraC protein contacts asymmetric sites in the Escherichia coli araFGH promoter. AB - AraC protein regulates the transcription of arabinose transport and catabolic operons in Escherichia coli through interaction with specific DNA sequences in the promoter regions of the operons. The interaction of AraC protein with two binding sites in the araFGH promoter was determined and compared to previously studied AraC binding sites in the araBAD promoter. Methylation and ethylation interference assays show that AraC protein binds along one side of the DNA to four adjacent major groove regions at each of the araFG1 and araFG2 sites. Mutations within any of the four regions of araFG1 greatly reduce protein binding in vitro. The promoter function in vivo is also greatly reduced, indicating that all four regions of the binding site are required. The chemical interference and genetic data, combined with the consensus sequence for AraC protein binding to ara promoters, support a binding motif in which two directly repeated units each span two adjacent turns of the DNA helix. The function of the two AraC binding sites was also examined. The proximal araFG1 site is required for promoter activation, whereas the distal araFG2 site has only a slight effect on the promoter activity. PMID- 1447223 TI - Calcium and collagen binding properties of osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 from bone. AB - Calcium binding properties of bone acidic glycoprotein-75, osteopontin, and bone sialoprotein were determined in 10 mM imidazole buffer (pH 6.8), containing either 60 mM KCl or 150 mM NaCl. Proteins assayed were first bound to nitrocellulose to mimic substrate-bound forms in vivo; retention of phosphoproteins was determined through use of radioiodinated tracers. Binding studies were carried out both as a function of calcium concentration and the amount of phosphoprotein. In the presence of 60 mM KCl, bone acidic glycoprotein 75 exhibited the largest calcium binding capacity (139 atoms/molecule at saturation), with bone sialoprotein intermediary (83 atoms/molecule) and osteopontin lowest (50 atoms/molecule). Sites detected for each phosphoprotein exhibited overall binding constants in the 0.5-1.0 mM extracellular range. In 150 mM NaCl and 1-2 mM total calcium, phosphoproteins bound between 72 and 19 mol of calcium/mol with the same relative order. Binding was proportional to amount of phosphoprotein in either salt condition. The presence of 5 mM calcium had a different effect on concentration-dependent binding to type I collagen for each phosphoprotein. Bone acidic glycoprotein-75 alone was found to undergo an unusual calcium-enhanced polymerization reaction, confirmed by light scattering measurements, wherein collagen binding was greatest with polymeric forms. These findings demonstrate that acidic phosphoproteins from bone bind calcium atoms with a range of capacities. Calcium appears to induce conformational changes in bone acidic glycoprotein-75 which influences its self-association and binding to different substrata. PMID- 1447224 TI - Induction of heparin-binding epidermal growth factor-like growth factor mRNA by phorbol ester and angiotensin II in rat aortic smooth muscle cells. AB - To determine whether the gene encoding the recently identified heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent smooth muscle cell (SMC) mitogen of macrophage origin, is transcribed and regulated in vascular SMC, we isolated cDNA clones encoding rat HB-EGF from a macrophage library. Using the rat HB-EGF cDNA as a probe for RNA blot analysis, we detected low levels of HB EGF mRNA in rat aortic SMC in culture. However, 20 nM 12-O-tetradecanoylphorbol 13-acetate (TPA) and 10(-6) M angiotensin II (AII) induced a marked increase in HB-EGF mRNA levels in rat aortic SMC (11- and 4.6-fold, respectively) that was both dose- and time-dependent. In response to TPA and AII, HB-EGF mRNA levels increased rapidly, peaked at 2 h, and returned to base line at 7 h. This effect of AII on HB-EGF induction was specific, as evidenced by the fact that it could be completely blocked by the AII antagonist saralasin. This is the first demonstration that HB-EGF is transcribed and regulated in SMC. The inducible transcription of this potent SMC mitogen gene in vascular SMC suggests that HB EGF may have an important autocrine role in the proliferation of SMC in vascular diseases such as atherosclerosis and hypertension. PMID- 1447225 TI - Dissociation of the contractile and hypertrophic effects of vasoconstrictor prostanoids in vascular smooth muscle. AB - To more clearly define the physiologic roles of thromboxane (TX)A2 and primary prostaglandins (PG) in vascular tissue we examined vascular contractility, cell signaling, and growth responses. The growth-promoting effects of (15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619; TXA2 agonist), PGF2 alpha, and PGE2 consisted of protein synthesis and proto-oncogene expression, but not DNA synthesis or cell proliferation. U46619 contracted rat aortas and increased cultured rat aortic vascular smooth muscle cell intracellular free calcium concentration [Ca2+]i, [3H]inositol monophosphate (IP) accumulation, myosin light chain phosphorylation, and protein synthesis ([3H]leucine incorporation) with EC50 values ranging from 10 to 50 nM. Each of these responses was inhibitable with the TXA2 receptor antagonist [1S]1 alpha,2 beta(5Z),3 beta,4 alpha-7-(3-[2- [(phenylamino)carbonyl]hydrazino]methyl)-7 oxabicyclo[2.2.1]hept-2- yl-5-heptenoic acid (SQ29548). In contrast, PGF2 alpha increased [Ca2+]i, [3H]IP, and protein synthesis with EC50 values of 30-230 nM but contracted rat aortas with an EC50 of 4800 nM. PGE2 increased [Ca2+]i, [3H]IP accumulation, protein synthesis, and contracted rat aortas with EC50 values of 2.5-3.5 microM. TXA2 receptor blockade prevented PGF2 alpha- and PGE2-induced aortic contraction and cell myosin light chain phosphorylation, but not cell signaling or protein synthesis. Binding studies to vascular smooth muscle TXA2 receptors using 1S-[1 alpha,2 beta(5Z),3 alpha(1E,3S),4 alpha]-7-(3-[3-hydroxy-4 (p- [125I]iodophenoxy)-1-butenyl]7-oxabicyclo[2.2.1]hept-2-yl)-5-hepte noic acid ([125I]BOP) showed U46619, SQ29548, PGF2 alpha, and PGE2 competition for TXA2 receptor binding at concentrations similar to their EC50 values for aortic contraction, while binding competition with [3H]PGF2 alpha and [3H]PGE2 demonstrated the specificity of [125I]BOP and SQ29548 for TXA2 receptors. The results suggest that 1) PGF2 alpha- and E2-stimulated vessel contraction is due to cross-agonism at vascular TXA2 receptors; 2) PGF2 alpha stimulates TXA2 receptor-independent vascular smooth muscle protein synthesis at nanomolar concentrations, consistent with an interaction at its primary receptor; and 3) TXA2 is a potent stimulus for vascular smooth muscle contraction and protein synthesis. We suggest that the main physiologic effect of PGF2 alpha may be as a stimulus for vascular smooth muscle cell hypertrophy, not as a contractile agonist. PMID- 1447226 TI - Sphingolipid transport in mitotic HeLa cells. AB - Mitotic and interphase HeLa cells were labeled with [3H]serine. Ceramide and its derivatives, lactosylceramide and sphingomyelin, were biosynthetically labeled under both conditions. Only in the absence of nocodazole, as the cells entered telophase, was an additional glycosphingolipid synthesized which was identified as GA2 (GalNAc(beta 1,4)Gal(beta 1,4)Glc(beta 1,1)Cer). Ceramide, the basic sphingolipid precursor, is synthesized in the endoplasmic reticulum, whereas its immediate derivatives are synthesized in early Golgi compartments. Transport of newly synthesized proteins from the endoplasmic reticulum to the Golgi is inhibited in mitotic cells while ceramide acquires early Golgi modifications under the same conditions, suggesting that ceramide can be delivered to the Golgi by a different route. Since GA2 is synthesized in late Golgi, its absence in mitotic cells strongly argues for an in vivo inhibition of intra-Golgi transport, an observation with important implications for the mechanism of Golgi division. PMID- 1447227 TI - A comparative study of ultrastructures of the interfaces between four kinds of surface-active ceramic and bone. AB - The interfaces between four kinds of surface-active ceramic and bone were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) using undecalcified specimens. The materials were Bioglass-type glass (Bioglass), Ceravital-type glass-ceramic (KGS), apatite- and wollastonite-containing glass ceramic (A-W.GC) and hydroxyapatite (HA). Particles of these materials, ranging between about 100 and 300 microns in diameter, were implanted into rat tibiae, and specimens were prepared for observation at 8 weeks after implantation. All materials were observed to bond to bone through a collagen-free layer consisting of fine apatite crystals distinct from those in bone. The crystals of this apatite layer and those of bone were intermingled at their interface, suggesting chemical bonding. In Bioglass, which had only a glassy phase, several tens of microns of the material surface had changed to such an apatite layer. In KGS and A-W.GC, which had macrocrystals in the glassy phase, an intervening apatite layer about 0.5 micron thick was observed between the materials and bone. Furthermore, fine apatite crystals were also observed among the macrocrystals near the surface of the materials. In HA, which had no glassy phase, an intervening apatite layer was much less distinct and sometimes absent. These differences were considered to be attributable to the differences in chemical composition, crystallization, and solubility of the materials. PMID- 1447228 TI - Influence of fibril length upon ePTFE graft healing and host modification of the implant. AB - Influence of fibril length (porosity) upon synthetic vascular graft healing has not been investigated in detail. The purpose of this study was to determine the dependence of neoendothelial healing, cellular response, and biocompatibility on the fibril length of expanded polytetrafluoroethylene (ePTFE) grafts with an internal diameter of 1.5 mm. ePTFE grafts of different fibril length, 20, 40, 60, and 90 microns, were implanted into the abdominal aorta of rats (n = 5 for each group). After 5 weeks, the implants were harvested and examined for neointimal and pseudointimal coverage by light microscopy and SEM. The hydroxyproline content of the implants was measured, and the distribution of collagen types was examined. The neointimal and pseudointimal coverage was related to the fibril length, and the neoendothelial healing was better on 60-microns and 90-microns grafts than on 20-microns and 40-microns grafts. The amount of hydroxyproline was also related to the fibril length, however, no significant difference could be observed between 60-microns and 90-microns grafts. Collagen types I and III were almost identically located in the middle portion of the implants. Our results demonstrate that the fibril length of ePTFE grafts affected neoendothelial healing and its affinity to collagen. PMID- 1447229 TI - Spatial and temporal changes in compliance following implantation of bioresorbable vascular grafts. AB - Compliance matching between the host vessel and vascular grafts used for small diameter arterial replacements is thought to be important for long-term patency. However, currently available grafts elicit fibroplastic reactions, resulting in decreasing compliance with time after implantation. Bioresorbable prostheses elicit ingrowth of myofibroblasts containing abundant contractile elements. This led us to investigate whether compliance of implanted bioresorbable prostheses decreased as a function of time and if the kinetics of change correlated with the progression of tissue ingrowth. Woven polyglactin 910 prostheses (10 mm x 4 mm i.d.) were implanted into adult NZW rabbit infrarenal aortas and replicates were harvested serially through 8 months. Control grafts were implanted, and immediately resected. Dynamic compliance was measured at 1-mm axial increments along each explant using a pulse duplicator apparatus which exposed the harvested samples to realistic pulsatile hemodynamics. Compliance was calculated for proximal, mid, and distal segments of each graft and averaged at each time point by grouping into control (zero time, n = 3), early (1-4 weeks, n = 13), and late (6-36 weeks, n = 9) explant periods. At late explant periods both proximal and distal compliance were significantly greater than mid graft compliance (p < .02 and p < .03, respectively). There was a significant increase in proximal compliance between early and late explant times (p < .01). Measured increases in mid and distal segment compliance over time did not reach statistical significance. Myofibroblast laden tissue ingrowth into the inner capsule followed macrophage phagocytosis and was nearly complete prior to the time that an increase in compliance was demonstrated. Thus since the major histologic episodes precede the change in compliance, these are not likely initiated by this biomechanical change. We hypothesize the graft resorption coupled with the ingrowth of more compliant tissue likely leads to the increased compliance of the graft material. PMID- 1447230 TI - Toxic effect of ethylene-oxide-sterilized freeze-dried bone allograft on human gingival fibroblasts. AB - Freeze-dried bone allograft (FDBA) which either had or had not been sterilized by exposure to ethylene oxide (EtO) prior to lyophilization was obtained from two commercial sources. EtO-sterilized FDBA was reexposed to EtO as a positive control. Gas chromatograph assays revealed that three out of four commercially obtained EtO sterilized FDBA had no detectable EtO, with one sample having 0.21 parts per million (PPM). Surprisingly, 0.24 PPM was detected in one sample which had not been sterilized with EtO gas. This was presumed due to contamination from a gas-sterilized rubber stopper. In the cell toxicity study, FDBA and human gingival fibroblasts (HGF) were added simultaneously, incubated for 72 h, and fixed and stained. Samples of FDBA sterilized with EtO which were free of EtO did not alter HGF growth. However, the positive control FDBA which contained 0.72 PPM EtO had a deleterious effect on HGF. FDBA with EtO residuals caused morphologic change in HGF. PMID- 1447231 TI - Porous polyurethane vascular prostheses with variable compliances. AB - A new technique for the preparation of porous vascular prostheses was investigated. Polyurethane solution (5 to 15 wt%) was injected into a mold. After freezing at low temperature (0 degrees C-196 degrees C), solvents were dissolved out with water at 0 degrees C to form porous tubes. The average pore size (several microns to 70 microns), pore occupation (10% to 51%), and compliance (3% to 35%) were easily changed by changing polyurethane concentration, freezing temperature, and freezing methods. Compliances could be decreased gradually by heat treatment. This technique can give a proper pore size (30-60 microns) for tissue ingrowth, and a suitable compliance for matching with arteries and veins. This method might give a desired compliant graft for artificial implantation with the presently valid medical polymers. PMID- 1447232 TI - Storage and elimination of titanium, aluminum, and vanadium salts, in vivo. AB - Hamsters were injected with titanium, aluminum, and vanadium salts either intraperitoneally or intramuscularly to study the transport, storage, and elimination of these metals. Blood samples were taken at 4 h or 24 h, and urine samples were taken at 24, 48, and 72 h. The hamsters were then injected weekly for 5 weeks after the initial injection. Blood and portions of the kidneys, liver, lung, and spleen were taken at sacrifice. All samples were analyzed for titanium, aluminum, and vanadium concentrations using graphite furnace atomic absorption spectroscopy (GFAAS). Titanium was found not to be excreted in the urine, was found in low levels in the blood, and was elevated over control in the kidney, liver, and spleen. Aluminum detection via GFAAS showed wide standard deviations and high levels in controls; however, aluminum was found to be excreted in the urine, and to be transported by the blood in the experimental animals. A small amount accumulated in the liver and spleen. Vanadium was excreted in high levels in the urine. A small amount was found in the blood, and the level in the organs was below the reliable detection limits. The rapid excretion of vanadium might be related to its solubility in physiological conditions, while the limited excretion of titanium may be related to its being insoluble in the physiologic environment. PMID- 1447233 TI - Tissue compatibility of collagen-silicone composites in a rat subcutaneous model. AB - Collagen-silicone composites were fabricated and tested for biocompatibility by subcutaneous implantation in rats. The silicone component consisted of addition cure or condensation cure sheets. The collagen component was either (a) a sponge layer 2 mm thick, (b) a thin film 12-20 microns thick, or (c) residual collagen bonded to or incorporated in the silicone rubber. Collagen sponges were mechanically bonded to silicone sheets, and collagen thin films and residual collagen were physically and chemically attached to epoxy-derivatized silicone sheets. Analysis of implanted samples showed that reduced capsule formation occurred around collagen sponge-silicone, compared to control silicone sheets. Only where the underlying silicone sheet, or interpenetrating silicone, was exposed to the tissue, did limited capsule formation occur. In contrast, thin capsule developed completely around silicone coated with a thin collagen film and around silicone bonded to residual collagen. Sponge-silicone composites and control silicone sheets were free of acute and chronic inflammation, except for occasional foreign body giant cells in sponge adjacent to silicone. Silicone coated with micron-thick collagen films exhibited some inflammation, but residual collagen-silicone did not. This study suggests that, to prevent capsule formation, a collagen coat must be of minimum thickness and surface coverage sufficient to prevent any contact between silicone and tissue. PMID- 1447234 TI - Avoidance of photoactivation in the epifluorescence video microscopic observation of thrombosis. PMID- 1447235 TI - Unnecessary arthroscopy. PMID- 1447236 TI - The significance of calf thrombi after total knee arthroplasty. AB - We reviewed the records of 1257 patients having 1625 total knee arthroplasties; all had pre-operative and postoperative perfusion lung scans and postoperative venograms which were classified as showing no thrombi, calf thrombi or proximal thrombi. Patients with calf thrombi were found to have a significantly greater risk for both symptomatic and asymptomatic pulmonary embolism compared with patients with no venographic thrombi. There were positive lung scans in 6.9% of patients with calf thrombi compared with 2.0% of patients with negative venograms (p < 0.001). Symptomatic pulmonary embolism occurred in 1.6% of patients with calf thrombi compared with 0.2% of patients with negative venograms (p = 0.034). The risk of pulmonary embolism was not significantly different between patients with treated proximal thrombi, and those with calf thrombi. Patients who develop deep-vein thrombosis despite prophylaxis are at increased risk for pulmonary embolism; these patients should receive treatment, or undergo follow-up studies to detect proximal propagation. PMID- 1447237 TI - Long-term results of total condylar knee arthroplasty in rheumatoid arthritis. AB - We have reviewed at an average period of ten years the results of 71 consecutive primary arthroplasties with the Insall-Burstein total condylar knee prosthesis in patients with rheumatoid arthritis. Their mean age at surgery was 52 years (24 to 72). At follow-up the overall results (Hospital for Special Surgery knee rating score) were excellent or good in 77%, fair in 11% and poor in 11%. There was residual pain in only 5% of patients with prostheses in situ; 58% could walk more than 500 m, and the median range of motion was 108 degrees. Eight knees had been revised. Five underwent arthrodesis because of deep infection and three needed revision arthroplasty for mechanical loosening. The crude survival rate of the arthroplasties was 89%. The presence of radiolucency around the tibial component correlated significantly with the severity of residual pain. PMID- 1447238 TI - Soft-tissue balance and alignment in medial unicompartmental knee arthroplasty. AB - We reviewed two similar groups of patients with medial osteoarthritis of the knee treated by unicompartmental arthroplasty. The group receiving an Oxford meniscal bearing implant, with no medial release, showed significantly better mechanical alignment than that receiving a fixed-bearing implant. Under-correction, with its ominous mechanical implications, was much more common with the fixed-bearing design. Over-correction was rare and was seen in both designs about equally. Degenerative stenosis of the intercondylar notch was common and appeared to put the anterior cruciate ligament at risk of rupture, especially after correction of the varus deformity. We consider that postoperative leg alignment and soft-tissue balance after unicompartmental knee replacement are determined more by the implant design and the surgical technique than by any variation in soft-tissue contracture. Release of the medial collateral ligament is not necessary for realignment, but a generous notchplasty is often needed to allow normal anterior cruciate ligament function. PMID- 1447239 TI - Isolated rupture of the popliteus with posterior tibial nerve palsy. AB - We report the case of a 59-year-old man with severe knee pain and inability to flex his toes or invert his plantar flexed foot after an external rotation injury to his knee. MRI showed rupture of the popliteus with a haematoma compressing the neurovascular bundle in the proximal calf, and electromyography demonstrated signs of an axonotmesis of the posterior tibial nerve. There was progressive nerve recovery over 24 weeks. Isolated rupture of the popliteus should be considered in any patient with an acute haemarthrosis, lateral tenderness and a stable knee, especially after an external rotation injury. PMID- 1447240 TI - A collarless cobalt-chrome femoral component in uncemented total hip arthroplasty. Five- to eight-year follow-up. AB - We implanted 57 uncemented cobalt-chrome porous-coated collarless femoral components into 51 patients (mean age 49 years). At review, five to eight years postoperatively, good or excellent results were recorded in 70% by the Mayo Clinic hip evaluation and in 84% by the Harris hip score. Revision for aseptic loosening of the femoral stem was necessary in only one hip. Thigh pain diminished with time and was present in only two hips at the time of review. Endosteal bone formation was seen at the junction of the smooth and the porous segments of the stem in 94% of hips and in 60% it continued after three years. In 90% of hips, proximal femoral atrophy did not progress after three years. Discontinuous radiolucent lines were seen around 30% of stems, most commonly in zones I, IV and VII. They were not progressive in 94% and their presence did not correlate with the clinical outcome. PMID- 1447241 TI - Cemented versus uncemented femoral components in the ring hip prosthesis. AB - A prospective, randomised and independently assessed trial of the Ring UPM total hip replacement showed that the quality of the early result was better if the femoral prosthesis was cemented than if it was not. More patients with cemented prostheses were painfree at four months (58% cemented:42% uncemented) and at one year (63% cemented:50% uncemented), but at two years pain relief was equal in both groups. At two years significantly more patients with cemented prostheses could walk without support (96% cemented:62% uncemented, p = 0.01 to 0.05). There is a need for more similar trials to compare the results of contemporary designs of cemented and uncemented total hip prostheses. PMID- 1447242 TI - Lymphocyte response to polymethylmethacrylate in loose total hip prostheses. AB - We investigated the lymphocyte-mediated immune response to polymethylmethacrylate bone cement in 26 patients who had revision surgery for aseptic loosening of cemented total hip arthroplasties, at a mean time of seven years after the first replacement. We studied eight patients with cemented total hip arthroplasties which were not loose as controls. Patch tests to polymethylmethacrylate bone cement were positive in 13 patients with loosening, and these patients had higher lymphoblast transformation values against polymethylmethacrylate bone cement patients with a negative skin reaction (p < 0.01) or those in the control group (p < 0.001). Specific monoclonal antibodies were used to assess the percentage of certain cells of the immune system according to their cluster of differentiation (CD). There was a higher number of total T and B lymphocytes (CD2 and CD22) and interleukin-2 receptor-positive lymphocytes (activated cells, CD25) in patients with loose prostheses. More CD25 lymphocytes were found in patients with positive patch tests. The activation of the lymphocyte-mediated immune response was not related to the presence or absence of aggressive granulomatous lesions at the cement-bone interface. PMID- 1447243 TI - Systemic distribution of wear debris after hip replacement. A cause for concern? AB - The production of particulate wear debris is a recognised complication of joint arthroplasty, but interest has concentrated on local tissue reactions and a possible association with implant loosening. The fate of wear products in the body remains unknown, although some of the metals used in the construction of orthopaedic implants are known to have toxic and oncogenic properties. We report histological and electron-microscopic evidence from two cases which shows that metallic debris can be identified in the lymphoreticular tissues of the body distant from the hip some years after joint replacement. The increase in the use of total arthroplasty in younger patients, the development of new alloys and the use of porous coatings must raise concern for the long-term effects of the accumulation of wear debris in the body. PMID- 1447244 TI - Classification of fractures of the tibial condyles. AB - We analysed 131 fractures of the tibial condyles in 130 patients, using a modification of the classification of Schatzker, McBroom and Bruce (1979). The patients were reviewed at an average of 7.6 years after the injury. Fifty-five (42%) fractures had been treated conservatively and 76 (58%) operatively. Medial unicondylar and medially tilted bicondylar fractures tended to redisplace into varus position and lateral unicondylar and laterally tilted bicondylar fractures into valgus. There were significant differences when the results were evaluated according to the methods of Hohl and Luck (1956) and Rasmussen (1973). Using our method in conservatively treated cases, the subjective results were acceptable in 49.1%, the functional results in 60.0% and the clinical results in 52.7%. In cases treated by operation the equivalent figures were 57.9%, 73.7% and 52.6%. The poorest results followed displaced medial condylar and medially tilted bicondylar fractures. Varus alignment of the tibial plateau was tolerated worse than valgus alignment. PMID- 1447245 TI - Fracture of the tibial spine in adults and children. A review of 31 cases. AB - We reviewed 19 adults and 12 children who had been treated for avulsion fractures of the tibial spine. Adult injuries have not previously been reported at length; most were caused by road-traffic accidents, and 68% were associated with other injuries, of which 58% were around the knee. The higher incidence of associated injuries in adults as compared with children, indicates that the injury is the result of greater energy and perhaps a different mechanism. The worse outcome in some adults was due to other associated intra-articular fractures and tears of the medial collateral ligament. Arthroscopy is useful in both diagnosis and treatment. Early accurate diagnosis and the correct treatment produce a good outcome. PMID- 1447246 TI - Absorbable pins of self-reinforced poly-L-lactic acid for fixation of fractures and osteotomies. AB - We reviewed 27 patients with small-fragment fractures or osteotomies treated by internal fixation with absorbable self-reinforced poly-L-lactide pins. The follow up time ranged from eight to 37 months. The two most common indications were chevron osteotomy of the first metatarsal bone for hallux valgus and displaced fracture of the radial head. No redisplacements occurred, and there were no signs of inflammatory foreign-body reaction. Biopsy in two patients 20 and 37 months after implantation showed that no polymeric material remained. PMID- 1447247 TI - Bone regrowth after surgical decompression for lumbar spinal stenosis. AB - We reviewed 40 patients treated surgically for lumbar stenosis at an average time of 8.6 years after operation. In 32, total laminectomy had been performed and in eight bilateral laminotomy, both at one or more levels. Of the 16 patients with degenerative spondylolisthesis, ten had had a concomitant spinal fusion. Patients were assigned to one of four groups according to the amount of bone regrowth: group 0 had no regrowth and groups I, II, and III, had mild, moderate or marked regrowth, respectively. Only 12% of the patients showed no bone regrowth; 48% were assigned to group I, 28% to group II and 12% to group III. Imaging studies showed varying degrees of recurrent stenosis in patients with moderate or marked bone regrowth. All patients with degenerative spondylolisthesis showed bone regrowth, which was more severe in those who had not had a fusion. The clinical results were satisfactory in most of the patients with mild or no bone regrowth and significantly less good in those with moderate or marked regrowth. In the group with degenerative spondylolisthesis, the proportion of satisfactory results was significantly higher in patients who had had spinal fusion. The long-term results of surgery for lumbar stenosis depend both upon the amount of bone regrowth and the degree of postoperative vertebral stability. PMID- 1447248 TI - Spinal cord monitoring during operative correction of neuromuscular scoliosis. AB - We report our experience of the monitoring of spinal somatosensory evoked potentials in 60 patients with neuromuscular scoliosis. In 15 cases a significant change occurred in the trace when a sublaminar wire was tightened. There were no postoperative neurological deficits attributable to the surgery. PMID- 1447249 TI - Upper-limb surgery for tetraplegia. AB - We reviewed the results of reconstruction of 97 upper limbs in a consecutive series of 57 tetraplegic patients, treated from 1982 to 1990. Of these, 49 had functional and eight had cosmetic reconstructions. The principal functional objectives were to provide active elbow extension, hook grip, and key pinch. Elbow extension was provided in 34 limbs, using deltoid-to-triceps transfer. Hook grip was provided in 58 limbs, mostly using extensor carpi radialis longus to flexor pollicis longus transfer, and key pinch in 68, mostly using brachioradialis to flexor pollicis longus transfer. Many other procedures were employed. At an average follow-up of 37 months, 70% had good or excellent subjective results, and objective measurements of function compared favourably with other series. Revisions were required for 11 active transfers and three tenodeses, while complications included rupture of anastomoses and problems with thumb interphalangeal joint stabilisation and wound healing. We report a reliable clinical method for differentiating between the activity of extensor carpi radialis longus and brevis and describe a successful new split flexor pollicis longus tenodesis for stabilising the thumb interphalangeal joint. Bilateral simultaneous surgery gave generally better results than did unilateral surgery. PMID- 1447250 TI - Osteoplastic repair of the atlas. AB - Fractures of the atlas constitute 4% to 12% of all bony injuries of the cervical spine; most are treated successfully by a cervical orthosis. Nonunion may be associated with neck or scalp pain on movement and is treated conventionally by some form of craniocervical fusion, which restricts head movement. The authors describe a case in which direct repair of the bony ring with a titanium plate and screws allowed bone healing, relieved the symptoms and maintained a full range of neck movements. The titanium plate interfered little with postoperative MR and CT imaging. PMID- 1447251 TI - A significant proportion of patients with osteosarcoma may belong to Li-Fraumeni cancer families. AB - We studied the pedigrees of 17 index patients with osteosarcoma, recording malignant disease and cause of death for first- and second-degree relatives. There were seven cancers and five cancer deaths per 2151.5 person-years in first degree relatives of osteosarcoma patients under the age of 50 years, a significantly greater incidence than in an age- and sex-matched population group (p < 0.001). This excess of malignancy was largely due to two families which fulfilled the criteria for the Li-Fraumeni cancer family syndrome. Both of these families were shown to have the genetic alterations in the p53 gene which have been implicated in this syndrome. Our study suggests that orthopaedic surgeons seeing new cases of osteosarcoma should arrange screening for familial malignancy. PMID- 1447252 TI - Massive femoral allografts followed for 22 to 36 years. Report of six cases. AB - Six massive femoral allografts followed up for 22 to 36 years are described. Three were intercalary, two were osteoarticular and one was a total femoral replacement. Their functional rating according to the Musculoskeletal Tumor Society System (Enneking 1987) averaged 82% (56 to 100). The radiographic score averaged 75% (48 to 100). Four allografts had suffered fractures, but three of these had later united to give good final scores. Our study shows that massive femoral allografts can function well for as long as 36 years. PMID- 1447253 TI - Management and outcome in tibial dysplasia. AB - Tibial dysplasia is a rare congenital deformity which must be distinguished from the more common fibular dysplasia. We have reviewed 24 patients with 35 affected legs. The classification system of Kalamchi and Dawe (1985) was found to be preferable to that of Jones, Barnes and Lloyd-Roberts (1978) as a guide to prognosis and management. We discuss the outcome of surgical treatment, recommending selective amputation for most cases. PMID- 1447254 TI - Modification of the L'Episcopo procedure for brachial plexus birth palsies. AB - We reviewed 19 children who had undergone a new modification of the L'Episcopo procedure for obstetric brachial plexus palsy. Through an axillary approach the latissimus dorsi tendon was re-routed anteriorly to the humerus and then anastomosed to the teres major tendon routed posteriorly. At an average follow-up of four years two months, the mean increase in shoulder abduction was 26 degrees and the mean increase in external rotation was 29 degrees. No neurovascular injury or postoperative infection occurred. Two patients had complications, and five did not gain from the procedure. The modified operation was relatively easier to perform and provided excellent cosmesis. PMID- 1447255 TI - Ehlers-Danlos syndrome with soft-tissue contractures. AB - We report four patients with a form of Ehlers-Danlos syndrome associated with soft-tissue contractures from birth and skin hyperalgesia. In early infancy, these cases were thought to be forms of arthrogryposis multiplex congenita, Larsen's syndrome or Marfan's syndrome. The characteristic triad of signs of Ehlers-Danlos disease gradually appeared from four to six years of age, allowing us to establish the correct diagnosis. We discuss the differential diagnosis of these connective-tissue disorders and the problems of the orthopaedic treatment of the associated joint deformities. Ehlers-Danlos syndrome is a heterogeneous group of metabolic diseases of collagen and our cases constitute a group which is distinct from the conventional types. PMID- 1447256 TI - Osteomyelitis of the calcaneum. AB - We reviewed 52 cases of osteomyelitis of the calcaneum. The clinical symptoms and signs were well defined, but different and less dramatic than those of long-bone osteomyelitis. Blood cultures were positive in 41% of cases and tissue cultures in 91%. Routine haematological tests were of little value, and radiological changes were often delayed, and were absent in 12%. With early diagnosis, treatment with antibiotics alone was usually effective, but complications and chronic disease were more likely if there was delay. Early diagnosis is the key to successful treatment. We describe a new physical sign and consider that diagnosis is almost always possible by clinical methods. PMID- 1447258 TI - Repair of cervical nerve roots proximal to the root ganglia. An experimental study in sheep. AB - An experimental model was established to investigate the possibility of repairing cervical nerve roots damaged above the dorsal root ganglion, as occurs in traction injuries of the brachial plexus. In four sheep the C6 root was divided and repaired within the dura using freeze-thawed muscle grafts. Recovery was assessed after eight months by electrophysiology and histology. Action potentials were recorded distal to the grafts in all four sheep, indicating regeneration of motor fibres. Histological examination showed regenerated fibres in the ventral roots below the grafts in all cases. These fibres could be traced distally to the brachial plexus. There was no evidence of recovery of dorsal roots. PMID- 1447257 TI - Medial meniscus replacement by a tendon autograft. Experiments in sheep. AB - In 20 skeletally mature female merino sheep, divided into four groups, we performed total medial meniscectomy, removal of the middle third of the patellar tendon, and tenotomy of the calcaneal tendon of the right hind leg. Group I (control) had no additional procedures. In the other three groups the medial meniscus was replaced by the middle third of the patellar tendon from the ipsilateral knee. The animals were killed at three (group II), six (group III), or 12 months (group IV) and the tendon-meniscus examined macroscopically, by light and scanning electron microscopy, and biomechanically. Remodelling of the tissue had taken place by 12 months but the failure stress and tensile modulus for the tendon-meniscus were lower than for the normal meniscus. Our evidence suggests that, in sheep, replacement of a meniscus by a tendon autograft may decrease the severity of the degenerative changes that occur after meniscectomy. PMID- 1447259 TI - Lipids and Dupuytren's disease. AB - We studied prospectively the relationship between serum lipids and Dupuytren's disease of the hand in 85 patients, 65 men and 20 women. The Dupuytren patients had significantly higher fasting serum cholesterol and triglyceride levels than did the controls (p < 0.001). The raised levels of serum lipids appeared to be associated with the pathogenesis of Dupuytren's disease, and this may help to explain the high incidence of Dupuytren's disease in alcoholic, diabetic and epileptic patients, since these conditions are also associated with raised serum lipid levels. PMID- 1447260 TI - Multicentric Gorham's disease. PMID- 1447261 TI - Pathological fracture due to retained surgical gauze. PMID- 1447262 TI - Failure of cementless hip replacements. PMID- 1447263 TI - Hydroxyapatite coating of prostheses. PMID- 1447264 TI - Ionising radiation and the orthopaedic surgeon. PMID- 1447265 TI - Thigh pain after hip arthroplasty. PMID- 1447266 TI - Test for calcaneal tendon rupture. PMID- 1447267 TI - Influence of coronary artery disease and left ventricular dysfunction on postoperative mortality in vascular surgery. AB - In an attempt to assess the influence of coronary artery disease and left ventricular dysfunction on postoperative mortality, 107 patients consisting of 32 AAA resections and 44 aortoiliac and 31 femoropopliteal reconstructions were reviewed. All patients had a preoperative coronary angiograms and underwent cardiac catheterization to prevent cardiac-related deaths. Severe coronary artery disease was angiographically demonstrated in 40.6% of AAA, 31.8% of AI and 3.2% of FP patients. Severe left ventricular dysfunction was found in 21.9% of AAA, 18.2% of AI and 6.5% of FP. Both of the early and 5 (45.5%) of the 11 late deaths were caused by cardiac events. The nine-year survival rate (53.3%) in the patients with a documented combination of coronary artery disease and left ventricular dysfunction was significantly lower than those in patients with normal disease, normal left ventricular function and either documented coronary artery disease or left ventricular dysfunction. It is suggested from this series that left ventricular dysfunction is one of the most important risk factors in patients who undergo AAA resection and AI reconstruction and that severe disease and postoperative mortality are possibly reduced by certain kinds of interventional coronary therapies. PMID- 1447268 TI - Influence of age on late results of valve replacement with porcine bioprostheses. AB - From 1976 to 1987, 877 patients, aged 13 to 80 years, underwent valve replacement with a Carpentier-Edwards porcine bioprosthesis--330 aortic, 421 mitral, and 126 multiple replacements. Patients were divided into 4 age groups, according to their age at the time of surgery: group I, less than 45 years (190 patients), group II, 45 to 54 years (203 patients), group III, 55 to 64 years (304), and group IV, 65 to 80 years (180 patients). Follow-up was 97.5 complete, averaged 85 months, and totalled 5624 patient-years. There were 79 early deaths (9%), and 181 late deaths. Overall survival was 80% and 64% at 5 and 10 years. Operative mortality increased significantly with age, and late survival was significantly better for group I. Intrinsic structural deterioration was the most common cause for reoperation and was responsible for 91% of the 143 reoperations. Incidence of intrinsic structural deterioration and of reoperation decreased significantly with increasing age, with respective freedom rates at 10 years of 57 and 54 in group I compared to 93 and 92% in group IV. Freedom from treatment failure (including early deaths, valve-related deaths, and valve-related complications with permanent disability) was similar for all 4 groups ranging from 78 to 85%, without any correlation with age of the patient. At last follow-up, a similar proportion of patients of each group remained asymptomatic, patients in functional class I ranging from 50 to 55%. Thus, age is a major determinant of durability of bioprostheses, but it does not appear to have a significant role in the overall success of valve replacement. PMID- 1447269 TI - Noninvasive assessment of internal thoracic artery for reoperative coronary artery surgery. AB - To determine whether previous sternotomy alters internal thoracic artery (ITA) anatomy and flow characteristics, a duplex scanner was used for noninvasive evaluation of the ITA in 59 patients who were scheduled for reoperative coronary artery bypass surgery. The left ITA was insonated through the third intercostal space by use of a duplex scanner (5.0 MHz probe). Measurements of the ITA diameter (mm) and peak systolic velocity (cm/sec) were obtained; ITA flow was calculated from velocity and cross-sectional area. These findings were compared with the values obtained from 105 patients who were scheduled to undergo first time (primary) coronary artery surgery during the same time period. In the reoperative group, preoperative mean ITA diameter was 2.26 +/- 0.06 mm; this was not significantly different from the primary group's mean ITA diameter of 2.15 +/ 0.04 mm (p = 0.09). Mean peak systolic velocity was 79.9 +/- 2.4 cm/sec and calculated systolic blood flow was 204.6 +/- 13.1 ml/min in the reoperative patients, as compared with 83.3 +/- 2.1 cm/sec and 189.5 +/- 8.6 ml/min in the primary group, respectively. Values were similar in both groups for the peak systolic velocity (p = 0.31) and calculated systolic blood flow (p = 0.32). These results suggest that previous heart surgery or sternotomy does not adversely affect ITA anatomy and flow characteristics. We conclude that ultrasonic imaging is an easily applicable technique for preoperative assessment of ITA in patients who have undergone previous sternotomy. PMID- 1447270 TI - Retroperfusion and balloon support to improve coronary revascularization. AB - Coronary venous retroperfusion and Intra-Aortic Balloon Pump (IABP) support are methods currently utilized to reduce ischemic damage prior to revascularization of acutely ischemic myocardium. This study was undertaken to determine whether combining coronary venous retroperfusion using Pressure Controlled Intermittent Coronary Sinus Occlusion (PICSO) with the IABP would result in improved salvage of ischemic myocardium. In 40 adult pigs, the second and third diagonal vessels were occluded with snares for 1 1/2 hours followed by 1/2 hours of cardioplegic arrest and 3 hours of reperfusion with the snares released. During the period of coronary occlusion prior to arrest, 10 pigs received the IABP, 10 had PICSO, 10 had PICSO+IABP, while 10 had no intervention (Unmodified). Ischemic damage was assessed by echocardiographic wall motion scores, myocardial pH, and the area of necrosis/area of risk using histochemical staining. Both PICSO and the IABP alone significantly reduced ischemic damage. However, the best wall motion scores, highest pH, and least necrosis was seen in the IABP+PICSO group. We conclude that the combination of coronary venous retroperfusion using PICSO and the IABP results in the most optimal recovery of acutely ischemic myocardium during emergent surgical revascularization. PMID- 1447271 TI - Preservation of the pulmonary valve during intracardiac repair of tetralogy of Fallot. AB - From January 1981 to December 1990, intracardiac repair of tetralogy of Fallot in 148 pediatric patients, with one surgical death, was directed toward preservation of the native pulmonary valve. Using the accepted preoperative angiographic criterion for the pulmonary valve annulus area (PVA) of 1.8 cm2/m2, 85 patients were candidates for transannular right ventricular outflow patch (TAP). However, in 54 patients with a mean PVA of 1.5 cm2/m2 (range 1.06-1.76), the valve was preserved without using TAP because the morphological changes (cusp thickening and annular distensibility) seemed acceptable for preservation in view of its probable hemodynamic efficiency and growth potential. A morphological classification of pulmonary valve changes has evolved. Retrospectively, 24 (77%) of the 31 patients with TAP had moderate to severe cusp thickening and ring rigidity; this incidence was significantly higher (p < 0.001) than that in preserved patients (18 of 54 or 33%). The incidence of morphological changes increased with operative age; that is, 2 of 13 (15%) patients younger than 1 year versus 23 of 40 (58%) patients older than 4 years (p < 0.01). All 54 patients with preserved pulmonary valves were catheterized one month postoperatively. The intraoperative right to left ventricular systolic pressure ratio (RVP/LVP) decreased significantly (p < 0.005) in one month, from a mean of 0.79 (range 0.44 1.36) to 0.57 (range 0.36-0.97). The PVA increased from a mean of 1.5 to 1.9 cm2/m2 (range 1.20-2.65), and the rate of its increase was significantly larger (p < 0.005) as operative age decreased. Pulmonary valve regurgitation of greater than mild degree occurred in 8 of 54 (15%) patients with the valve preserved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447272 TI - Internal mammary artery bypass: thirteen years of experience. Influence of angina and survival in 5125 patients. AB - Internal mammary artery (IMA) bypass to the anterior descending coronary artery (ADA) was performed in 5125 patients from January 1978 to December 1990. The average age of patients was 68 years; males accounted for 68% (3485 patients) and 82% (4203) were NYHA Class III. Left ventricular function was impaired (ejection fraction < 40%) in 68% (3485 patients). The average number of additional saphenous vein graft (SVG) per patient was 2.2. Operative mortality was 1.8%. Mediastinitis occurred in 51 patients (1.0%). Reoperation for bleeding was necessary in 56 patients (1.1%). Perioperative myocardial infarction was seen in 102 patients (2.0%) and neurological complications occurred in 51 patients (1%). Repeat coronary angiography was performed in 1414 patients (28%) and demonstrated a patency rate of 96% in IMA grafts and 75% in SVG grafts (p < 0.001). Survival at 13 years was 80% from all causes and 90% when non-cardiac deaths were excluded. Recurrence of angina occurred in 768 patients (15%) and reoperation or PTCA was performed in 61 (1.2%). During the same time period, 2345 patients underwent coronary artery bypass utilizing solely SVG. Survival at 13 years was 68% from all causes and 78% when non-cardiac deaths were excluded (p < 0.001). Recurrent angina was present in 727 patients (31%) (< 0.001). This data suggests that long-term probability of cumulative survival and occlusion free survival were significantly greater and the probability of recurrent angina and reoperative CABG and death from cardiac causes were significantly less in the IMA patients and should be the conduit of choice in coronary bypass surgery. PMID- 1447273 TI - Simple hypothermic retrograde cerebral perfusion during aortic arch surgery. AB - We have found that retrograde cerebral perfusion can be performed by simply elevating central venous pressure during aortic arch surgery. During hypothermia (15 degrees C) venous blood rich in oxygen perfuses the brain, while the lower half of the body is perfused with the descending aorta occluded. Fourteen cases of aortic arch aneurysm (11 males, 3 females) were treated by this method and evaluated. Median and lateral thoracotomies were performed in 6 and 8 cases, respectively. Cerebral circulatory arrest time was 65 +/- 14 min (32-93 min), and significant oxygen and lactate extraction were noted in the brain. Eleven cases showed no neurologic deficit, but loss of consciousness due to other causes occurred in 3. In conclusion, this method maintained the aerobic metabolism of the brain and protected it during prolonged cerebral circulatory arrest, simplifying the procedure and permitting both median and lateral approaches. PMID- 1447274 TI - Haemolysis following mitral valve repair. AB - We report the unusual occurrence of severe intra-vascular haemolysis following mitral valve repair. Mild to moderate mitral regurgitation was detected after repair, but severe haemolysis was the only indication for re-operation. Following prosthetic valve replacement there was an immediate cessation of haemolysis. We postulate that a small regurgitant jet directed against the teflon pledgets used in the repair was the reason for the haemolysis. PMID- 1447275 TI - Extensive surgery for primary malignant lymphoma of the heart. AB - The surgical treatment of primary malignant lymphoma of the heart in a 43-year old man is reported. The tumor was extensively resected together with the right atrial wall and both venae cavae, and the resulting defect was repaired with a bovine pericardial patch. The postoperative course was fairly stable for more than 7 months following surgery, under a regular chemotherapy regimen. The patient died of acute pneumonia on the 234th postoperative day. The autopsy findings confirmed the diagnosis of primary malignant lymphoma of the heart. PMID- 1447276 TI - Results of long-term venacavography study after placement of a Greenfield vena caval filter. AB - Digital subtraction venacavography (DSV) as a follow-up examination was performed in 46 patients after placement of a standard stainless steel Greenfield vena caval filter (SGF). DSV is an exact method of visualizing the lumen of the inferior vena cava as well as intraluminal or captured thrombi. Eccentric filters with an angulation of more than 15 degrees were found in 8 patients causing a higher risk of pulmonary embolism from smaller emboli and propagating thrombi. Penetration of the caval wall by filter struts was however frequent (41%), without any damage to adjacent structures as demonstrated by CT scans. The long term caval patency rate was 90%, with 4 cases of caval thrombosis. Two patients with an occluded inferior vena cava showed no venostasis. Although changes of the filter position usually remain asymptomatic, regular follow-up examinations seem necessary to recognize any impairment of the filter's clot trapping efficiency. Filters should only be used in patients with a risk of recurrent pulmonary embolism despite anticoagulation and patients with contraindications to anticoagulation therapy. PMID- 1447277 TI - Effects of estrogen on vein grafts. AB - The effect of estrogen on veins was evaluated in vitro and in vivo in three species. 17 beta-estradiol did not significantly alter 3H-thymidine uptake in vitro in segments from either canine femoral or human saphenous veins. In vivo in a rabbit carotid vein graft model, 17 beta-estradiol administration did not affect the development of intimal hyperplasia but was associated with a higher rate of graft thrombosis. These data suggest that the effects of estrogen on veins differs from the effects reported in arteries. These differences were seen both in vitro in veins taken from their normal location and in vivo in veins placed in the arterial circulation. PMID- 1447278 TI - Endothelial cell injury in human saphenous veins following use of a circular valvulotome. AB - With increasing use of nonreversed saphenous vein as a bypass conduit (either in situ or translocated) several techniques of valve ablation are used. The present study was designed to assess the extent of endothelial damage caused by a circular blade valvulotome. PMID- 1447279 TI - Do cytokines play a role in skeletal muscle ischemia and reperfusion? AB - Cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF) are known to mediate host cell response to sepsis, trauma, and myocardial ischemia. We have previously found increased levels of IL-1 in the venous effluent during the reperfusion phase of skeletal muscle ischemia in a canine model. This study was done to evaluate whether TNF also played a role in skeletal muscle ischemia reperfusion injury since IL-1 and TNF have inter-related functions. In twelve adult mongrel dogs (28-32 kg) one gracilis muscle was subjected to six hours of normothermic ischemia followed by normothermic reperfusion. The contralateral side served as a control and remained normally perfused throughout the experiment. Gracilis venous samples were collected at pre-ischemia and one hour of reperfusion. Systemic (arterial) blood samples were taken simultaneously with the venous samples at one hour of reperfusion. At the end of the experiment the muscles were harvested and amount of necrosis quantitated by serial transections, nitroblue tetrazolium staining and computerized planimetry. Muscle necrosis on the experimental side was found to be 48.86 +/- 5.37%. Sera were analyzed for TNF activity using a bioassay. TNF levels in the gracilis venous effluent at one hour of reperfusion were not significantly different from the simultaneous systemic (arterial) levels (27.15 +/- 5.05 pg/ml vs 18.23 +/- 4.27 pg/ml). Pre-ischemic levels of TNF were 96.50 +/- 20.12 pg/ml, which was significantly higher than either venous or arterial levels obtained after one hour of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447280 TI - Concomitant subclavian and carotid artery disease: the need for a combined surgical correction. AB - To determine the importance of carotid artery disease in patients undergoing revascularization of the proximal subclavian artery for a subclavian steal syndrome, an 18-year experience of 55 patients was reviewed. Concomitant carotid artery disease (> 50% stenosis) was present in 35 patients (Group I: 63.6%). Twenty patients (Group II: 36.4%) had no evidence of hemodynamically significant carotid disease. Twenty-five patients in Group I (Group IA: 71.4%) were treated by endarterectomy (CEA) for all their carotid lesions while one or both carotid lesions were left untreated in 10 patients (Group IB: 28.6%). The actuarial 5 year freedom rate from neurological events was 87.2% in Group IA, 34.9% in Group IB (p < 0.001) and 100% in Group II (Group IB vs. II, p < 0.001; Group IA vs. Group II, p = ns). All untreated carotid lesions had a deleterious effect on the early and late functional results after surgical reconstruction of the subclavian artery. We conclude that the combined correction of subclavian and carotid lesions should be recommended in every case. PMID- 1447281 TI - Temporal arteritis. Clinical implications for the vascular surgeon. AB - Temporal arteritis is a systemic disease with local temporal artery symptoms, generalized constitutional symptoms and ocular involvement which affects the elderly. A study was undertaken to assess the clinical features of patients with temporal arteritis in a large multispecialty clinic practice. The study group consisted of 516 patients with clinical suspicion of temporal arteritis, of which 97 (18.8%) had a positive biopsy for arteritis. The records of these 74 females and 23 males were retrospectively reviewed for clinical implications of the disease. The average age of the cohort was 71.7 years, and male to female ratio was 1:3.2. There were 95 caucasians and 2 blacks. The most common clinical findings at presentation were abnormal temporal artery (65.9%), headache (64.8%), myalgias or arthralgias (46.6%), visual symptoms (37.1%) and fever (35.1%). Multiple symptoms were present in 97% of the patients. The erythrocyte sedimentation rate was > 50 mm per hour in 91% of patients. Corticosteroids were used to treat 95/97 patients. Twenty-seven (28%) of the patients completed treatment over an average 36.3 months. Sixty-eight (72%) other patients were either lost to follow-up, died, or continue on therapy. Complications of corticosteroid treatment occurred in 43 (44.3%) of patients, and complications of temporal arteritis occurred in 14 (14.4%). A review of biopsy data showed no difference in length of biopsy or yield of biopsy in the patients with positive and the patients with negative histology. Temporal arteritis is a systemic disease which responds well to corticosteroid treatment. Complications of the disease as well as of treatment make definitive diagnosis imperative. PMID- 1447282 TI - False aneurysms after aortic operations. AB - Between 1980 and August 1991, we encountered 11 non-infected aortic pseudoaneurysms after aortic surgery. The interval between the initial operation and revision varied from 1.8 to 26.8 years (mean 15.2 years). Three were found more than 20 years after operation. Pulling off of and degrading of the silk sutures were considered to be the causes. All patients underwent operative correction without mortality. In thoracic aortic pseudoaneurysm repair, a temporary bypass between the right axillary artery and left external iliac artery was generally adopted. There was no need for heparinization with this technique. PMID- 1447283 TI - Esmarch's bandage technique in distal bypass surgery. AB - Esmarch's rubber bandage technique has been applied to 49 distal bypass surgeries in 46 patients during the past ten years. The primary and secondary patency rates at 5 years after femoro-tibial bypass surgery were 82% and 92%, respectively. This technique has the following advantages: (1) it minimizes surgical injury of the arterial wall because there is less dissection around the anastomotic site; (2) it decreases scar formation in the anastomotic area after surgery; (3) it maintains abundant muscular blood flow by preserving small branches to muscles, and (4) it provides a bloodless surgical field and easy handling for fine sutures without using vascular clamps. We consider that the avoidance of long circumferential dissection of the artery may play an important role in improving long-term patency in distal bypass surgery. PMID- 1447284 TI - Response of arterial smooth muscle cells to laminar flow. AB - This study was designed to determine whether laminar flow influences the proliferation rate and morphology of smooth muscle cells (SMC) in culture. Bovine aortic SMC were subjected to a shear stress of 6 dyne/cm2. The control group was subjected to similar incubation conditions without flow. Flow cytometry demonstrated decreased proliferation rate in SMC subjected to laminar flow. This phenomenon was still evident 24 hours after flow cessation. SMC were examined by light and electron microscopy. SMC subjected to laminar flow aligned along the direction of flow assuming a spheric morphology. These changes were reversible after a 48-hour resting period. The degree of organization of actin, tubulin and other microfilaments was evaluated by indirect immunofluorescence. SMC subjected to shear stress showed a clear reorganization of the cytoskeleton with expression of stress fibres. These changes were reversible after a 48-hour resting period. These findings may contribute to understanding the mechanisms by which SMC in vivo respond to forces generated by blood flowing under pressure. PMID- 1447285 TI - Isolated popliteal artery occlusion in the young. AB - Three young patients with an isolated popliteal artery occlusion are presented, two with severe claudication and the third with a critical ischaemic foot. The work-up of these patients leads to certain aetiologic possibilities: microtrauma, smoking and contraceptive pills. Two of our patients underwent thromboembolectomy, the third managed conservatively. The follow-up was between six months and seven years and up to now all three patients remain well. PMID- 1447286 TI - Hepatic artery aneurysm simulating a pancreatic mass. AB - A 61-year-old man presented with a mass in the right upper quadrant of the abdomen. Computer tomography scanning (CT) had initially suggested that the location was in the head of the pancreas. Further examination with ultrasonography and celiac angiography documented that the mass was an aneurysm of the common hepatic artery. The successful approach to its surgical management is described. PMID- 1447287 TI - Assembly and localization of the U1-specific snRNP C protein in the amphibian oocyte. AB - To study the intranuclear localization of the U1-specific snRNP C protein and its assembly into U1 snRNPs, we injected transcripts encoding a myc-tagged C protein into amphibian oocytes. The distribution of protein translated from the injected RNA was essentially the same in continuous and pulse-label experiments. In both cases the C protein localized within the germinal vesicle in those structures known to contain U1 snRNPs, namely the lampbrush chromosome loops and hundreds of extrachromosomal granules called snurposomes. Oocytes were also injected with an antisense oligodeoxynucleotide that caused truncation of U1 snRNA at the 5' end. In these oocytes, myc-tagged C protein localized normally in the germinal vesicle and could be immunoprecipitated together with truncated U1 snRNA. These experiments suggest that the C protein can enter the germinal vesicle on its own and there associate with previously assembled U1 snRNPs. In transfected tissue culture cells, the myc-tagged C protein localized within the nucleus in a speckled pattern similar to that of endogenous U1 snRNPs. PMID- 1447288 TI - Restricted distribution of mRNA produced from a single nucleus in hybrid myotubes. AB - Although the proteins encoded by a single nucleus in multinucleated myotubes have a wide range of distributions within the myofiber, little is known about the distributions of their mRNAs. We have used hybrid myotubes in which one or a few nuclei are derived from myoblasts that express nonmuscle proteins to investigate this question. We find that three different mRNAs, encoding proteins that are, respectively, nuclear, cytoplasmic, and targeted to the ER, have similar distributions within myotubes. Each is confined to an area within approximately 100 microns of the nucleus that expresses it. PMID- 1447289 TI - Multiple GTP-binding proteins regulate vesicular transport from the ER to Golgi membranes. AB - Using indirect immunofluorescence we have examined the effects of reagents which inhibit the function of ras-related rab small GTP-binding proteins and heterotrimeric G alpha beta gamma proteins in ER to Golgi transport. Export from the ER was inhibited by an antibody towards rab1B and an NH2-terminal peptide which inhibits ARF function (Balch, W. E., R. A. Kahn, and R. Schwaninger. 1992. J. Biol. Chem. 267:13053-13061), suggesting that both of these small GTP-binding proteins are essential for the transport vesicle formation. Export from the ER was also potently inhibited by mastoparan, a peptide which mimics G protein binding regions of seven transmembrane spanning receptors activating and uncoupling heterotrimeric G proteins from their cognate receptors. Consistent with this result, purified beta gamma subunits inhibited the export of VSV-G from the ER suggesting an initial event in transport vesicle assembly was regulated by a heterotrimeric G protein. In contrast, incubation in the presence of GTP gamma S or AIF(3-5) resulted in the accumulation of transported protein in different populations of punctate pre-Golgi intermediates distributed throughout the cytoplasm of the cell. Finally, a peptide which is believed to antagonize the interaction of rab proteins with putative downstream effector molecules inhibited transport at a later step preceding delivery to the cis Golgi compartment, similar to the site of accumulation of transported protein in the absence of NSF or calcium (Plutner, H., H. W. Davidson, J. Saraste, and W. E. Balch. 1992. J. Cell Biol. 119:1097-1116). These results are consistent with the hypothesis that multiple GTP-binding proteins including a heterotrimeric G protein(s), ARF and rab1 differentially regulate steps in the transport of protein between early compartments of the secretory pathway. The concept that G protein-coupled receptors gate the export of protein from the ER is discussed. PMID- 1447291 TI - Evidence for a novel route of wheat storage proteins to vacuoles. AB - Wheat seed storage proteins are deposited in protein bodies (PB) inside vacuoles, but their subcellular site of aggregation and their route to vacuoles are still controversial. In the present work, an ultra structural analysis of developing wheat endosperm at early to mid maturation was performed to address these issues. Golgi complexes were rarely detected, indicating that their role in wheat storage protein transport is limited. In contrast, a considerable amount of PB was detected in the cytoplasm. Many of these PB were surrounded by RER membranes and were enlarged by fusion of smaller PB. Small, electron lucent vesicles were detected around the surfaces of the PB in the cytoplasm, or attached to them, suggesting that such attachments and subsequent fusion of the vesicles with each other lead to the formation of small vacuoles containing PB inclusions. Immunogold labeling with serum raised against yeast-BiP, an ER-localized protein, demonstrated that the wheat BiP homolog was present within the PB in the cytoplasm as well as inside vacuoles. This confirmed that the PB were formed within the RER and that the Golgi complex was not involved in their transport to vacuoles. It is concluded that a considerable part of the wheat storage proteins aggregate into PB within the RER and are then transported as intact PB to the vacuoles by a novel route that does not utilize the Golgi complex. PMID- 1447290 TI - Morphological analysis of protein transport from the ER to Golgi membranes in digitonin-permeabilized cells: role of the P58 containing compartment. AB - The glycoside digitonin was used to selectively permeabilize the plasma membrane exposing functionally and morphologically intact ER and Golgi compartments. Permeabilized cells efficiently transported vesicular stomatitis virus glycoprotein (VSV-G) through sealed, membrane-bound compartments in an ATP and cytosol dependent fashion. Transport was vectorial. VSV-G protein was first transported to punctate structures which colocalized with p58 (a putative marker for peripheral punctate pre-Golgi intermediates and the cis-Golgi network) before delivery to the medial Golgi compartments containing alpha-1,2-mannosidase II and processing of VSV-G to endoglycosidase H resistant forms. Exit from the ER was inhibited by an antibody recognizing the carboxyl-terminus of VSV-G. In contrast, VSV-G protein colocalized with p58 in the absence of Ca2+ or the presence of an antibody which inhibits the transport component NSF (SEC18). These studies demonstrate that digitonin permeabilized cells can be used to efficiently reconstitute the early secretory pathway in vitro, allowing a direct comparison of the morphological and biochemical events involved in vesicular tafficking, and identifying a key role for the p58 containing compartment in ER to Golgi transport. PMID- 1447292 TI - Glycosome assembly in trypanosomes: variations in the acceptable degeneracy of a COOH-terminal microbody targeting signal. AB - Trypanosomes compartmentalize most of their glycolytic enzymes in a peroxisome like microbody, the glycosome. The specificity of glycosomal targeting was examined by expression of chloramphenicol acetyltransferase fusion proteins in trypanosomes and monkey cells. Compartmentalization was assessed by cell fractionation, differential detergent permeabilization, and immunofluorescence. The targeting signal of trypanosome phosphoglycerate kinase resides in the COOH terminal hexapeptide, NRWSSL; a basic amino acid is not required. The minimal targeting signal is, as for mammalian cells, a COOH-terminal tripeptide related to -SKL. However, the acceptable degeneracy of the signal for glycosomal targeting in trypanosomes is considerably greater than that for peroxisomal targeting in mammals, with particularly relaxed requirements in the penultimate position. PMID- 1447293 TI - Effects of null mutations and overexpression of capping protein on morphogenesis, actin distribution and polarized secretion in yeast. AB - CAP1, the gene encoding the alpha subunit of Saccharomyces cerevisiae capping protein, was cloned using a probe prepared by PCR with primers based on the amino acid sequence of purified alpha subunit peptides. The sequence is similar to that of capping protein alpha subunits of other species but not to that of the S. cerevisiae capping protein beta subunit or any other protein. Null mutants of capping protein, prepared by deletion of the coding region of CAP1 and CAP2 separately or together, are viable and have a similar phenotype. Deletion of the gene for one subunit leads to a loss of protein for the other subunit. The null mutant has a severe deficit of actin cables and an increased number of actin spots in the mother. Cells are round and relatively large. These features are heterogeneous within a population of cells and vary with genetic background. Overexpression of CAP1 and CAP2 also causes loss of actin cables and cell enlargement, as well as the additional traits of aberrant morphogenesis and cell wall thickening. Capping protein null strains and overexpression strains exhibited normal polarized secretion during bud growth as demonstrated by labeling with fluoresceinated Con A. Projection formation and chitin deposition in response to mating pheromone, mating efficiency, and bud site selection were also normal in capping protein null strains. In addition, bulk secretion of invertase was unimpaired. These data indicate that actin cables are not required for polarized secretion in S. cerevisiae. PMID- 1447294 TI - Cytosol- and clathrin-dependent stimulation of endocytosis in vitro by purified adaptors. AB - Using stage-specific assays for receptor-mediated endocytosis of transferrin (Tfn) into perforated A431 cells we show that purified adaptors stimulate coated pit assembly and ligand sequestration into deeply invaginated coated pits. Late events in endocytosis involving membrane fission and coated vesicle budding which lead to the internalization of Tfn are unaffected. AP2, plasma membrane adaptors, are active at physiological concentrations, whereas AP1, Golgi adaptors, are inactive. Adaptor-dependent stimulation of Tfn sequestration requires cytosolic clathrin, but is unaffected by clathrin purified from coated vesicles suggesting that soluble and assembled clathrin pools are functionally distinct. In addition to adaptors and cytosolic clathrin other, as yet unidentified, cytosolic factors are also required for efficient coated pit invagination. These results provide new insight into the mechanisms and regulation of coated pit assembly and invagination. PMID- 1447295 TI - 5'nucleotidase is sorted to the apical domain of hepatocytes via an indirect route. AB - In hepatocytes, all newly synthesized plasma membrane (PM) proteins so far studied arrive first at the basolateral domain; apically destined proteins are subsequently endocytosed and sorted to the apical domain via transcytosis. A mechanism for the sorting of newly synthesized glycophosphatidylinositol (GPI) linked proteins has been proposed whereby they associate in lipid microdomains in the trans-Golgi network and then arrive at the apical domain directly. Such a mechanism poses a potential exception to the hepatocyte rule. We have used pulse chase techniques in conjunction with subcellular fractionation to compare the trafficking of 5' nucleotidase (5NT), an endogenous GPI-anchored protein of hepatocytes, with two transmembrane proteins. Using a one-step fractionation technique to separate a highly enriched fraction of Golgi-derived membranes from ER and PM, we find that both 5NT and the polymeric IgA receptor (pIgAR) traverse the ER and Golgi apparatus with high efficiency. Using a method that resolves PM vesicles derived from the apical and basolateral domains, we find that 5NT first appears at the basolateral domain as early as 30 min of chase. However the subsequent redistribution to the apical domain requires > 3.5 h of chase to reach steady state. This rate of transcytosis is much slower than that observed for dipeptidylpeptidase IV, an apical protein anchored via a single transmembrane domain. We propose that the slow rate of transcytosis is related to the fact that GPI-linked proteins are excluded from clathrin-coated pits/vesicles, and instead must be endocytosed via a slower nonclathrin pathway. PMID- 1447296 TI - Direct visualization of the dystrophin network on skeletal muscle fiber membrane. AB - Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene locus, is expressed on the muscle fiber surface. One key to further understanding of the cellular function of dystrophin would be extended knowledge about its subcellular organization. We have shown that dystrophin molecules are not uniformly distributed over the humen, rat, and mouse skeletal muscle fiber surface using three independent methods. Incubation of single-teased muscle fibers with antibodies to dystrophin revealed a network of denser transversal rings (costameres) and finer longitudinal interconnections. Double staining of longitudinal semithin cryosections for dystrophin and alpha-actinin showed spatial juxtaposition of the costameres to the Z bands. Where peripheral myonuclei precluded direct contact of dystrophin to the Z bands the organization of dystrophin was altered into lacunae harboring the myonucleus. These lacunae were surrounded by a dystrophin ring and covered by a more uniform dystrophin veil. Mechanical skinning of single-teased fibers revealed tighter mechanical connection of dystrophin to the plasma membrane than to the underlying internal domain of the muscle fiber. The entire dystrophin network remained preserved in its structure on isolated muscle sarcolemma and identical in appearance to the pattern observed on teased fibers. Therefore, connection of defined areas of plasma membrane or its constituents such as ion channels to single sarcomeres might be a potential function exerted by dystrophin alone or in conjunction with other submembrane cytoskeletal proteins. PMID- 1447297 TI - Differential localization of Acanthamoeba myosin I isoforms. AB - Acanthamoeba myosins IA and IB were localized by immunofluorescence and immunoelectron microscopy in vegetative and phagocytosing cells and the total cell contents of myosins IA, IB, and IC were quantified by immunoprecipitation. The quantitative distributions of the three myosin I isoforms were then calculated from these data and the previously determined localization of myosin IC. Myosin IA occurs almost exclusively in the cytoplasm, where it accounts for approximately 50% of the total myosin I, in the cortex beneath phagocytic cups and in association with small cytoplasmic vesicles. Myosin IB is the predominant isoform associated with the plasma membrane, large vacuole membranes and phagocytic membranes and accounts for almost half of the total myosin I in the cytoplasm. Myosin IC accounts for a significant fraction of the total myosin I associated with the plasma membrane and large vacuole membranes and is the only myosin I isoform associated with the contractile vacuole membrane. These data suggest that myosin IA may function in cytoplasmic vesicle transport and myosin I mediated cortical contraction, myosin IB in pseudopod extension and phagocytosis, and myosin IC in contractile vacuole function. In addition, endogenous and exogenously added myosins IA and IB appeared to be associated with the cytoplasmic surface of different subpopulations of purified plasma membranes implying that the different myosin I isoforms are targeted to specific membrane domains through a mechanism that involves more than the affinity of the myosins for anionic phospholipids. PMID- 1447298 TI - Maternal effect mutations of the sponge locus affect actin cytoskeletal rearrangements in Drosophila melanogaster embryos. AB - In the syncytial blastoderm stage of Drosophila embryogenesis, dome-shaped actin "caps" are observed above the interphase nuclei. During mitosis, this actin rearranges to participate in the formation of pseudocleavage furrows, transient membranous invaginations between dividing nuclei. Embryos laid by homozygous sponge mothers lack these characteristic actin structures, but retain other actin associated structures and processes. Our results indicate that the sponge product is specifically required for the formation of actin caps and metaphase furrows. The specificity of the sponge phenotype permits dissection of both the process of actin cap formation and the functions of actin caps and metaphase furrows. Our data demonstrate that the distribution of actin binding protein 13D2 is unaffected in sponge embryos and suggest that 13D2 is upstream of actin in cortical cap assembly. Although actin caps and metaphase furrows have been implicated in maintaining the fidelity of nuclear division and the positions of nuclei within the cortex, our observations indicate that these structures are dispensible during the early syncytial blastoderm cell cycles. A later requirement for actin metaphase furrows in preventing the nucleation of mitotic spindles between inappropriate centrosomes is observed. Furthermore, the formation of actin caps and metaphase furrows is not a prerequisite for the formation of the hexagonal array of actin instrumental in the conversion of the syncytial embryo into a cellular blastoderm. PMID- 1447299 TI - Nerve growth cone lamellipodia contain two populations of actin filaments that differ in organization and polarity. AB - The organization and polarity of actin filaments in neuronal growth cones was studied with negative stain and freeze-etch EM using a permeabilization protocol that caused little detectable change in morphology when cultured nerve growth cones were observed by video-enhanced differential interference contrast microscopy. The lamellipodial actin cytoskeleton was composed of two distinct subpopulations: a population of 40-100-nm-wide filament bundles radiated from the leading edge, and a second population of branching short filaments filled the volume between the dorsal and ventral membrane surfaces. Together, the two populations formed the three-dimensional structural network seen within expanding lamellipodia. Interaction of the actin filaments with the ventral membrane surface occurred along the length of the filaments via membrane associated proteins. The long bundled filament population was primarily involved in these interactions. The filament tips of either population appeared to interact with the membrane only at the leading edge; this interaction was mediated by a globular Triton-insoluble material. Actin filament polarity was determined by decoration with myosin S1 or heavy meromyosin. Previous reports have suggested that the polarity of the actin filaments in motile cells is uniform, with the barbed ends toward the leading edge. We observed that the actin filament polarity within growth cone lamellipodia is not uniform; although the predominant orientation was with the barbed end toward the leading edge (47-56%), 22-25% of the filaments had the opposite orientation with their pointed ends toward the leading edge, and 19-31% ran parallel to the leading edge. The two actin filament populations display distinct polarity profiles: the longer filaments appear to be oriented predominantly with their barbed ends toward the leading edge, whereas the short filaments appear to be randomly oriented. The different length, organization and polarity of the two filament populations suggest that they differ in stability and function. The population of bundled long filaments, which appeared to be more ventrally located and in contact with membrane proteins, may be more stable than the population of short branched filaments. The location, organization, and polarity of the long bundled filaments suggest that they may be necessary for the expansion of lamellipodia and for the production of tension mediated by receptors to substrate adhesion molecules. PMID- 1447300 TI - Thymosin beta 4 sequesters the majority of G-actin in resting human polymorphonuclear leukocytes. AB - Thymosin beta 4 (T beta 4), a 5-kD peptide which binds G-actin and inhibits its polymerization (Safer, D., M. Elzinga, and V. T. Nachmias. 1991. J. Biol. Chem. 266:4029-4032), appears to be the major G-actin sequestering protein in human PMNs. In support of a previous study by Hannappel, E., and M. Van Kampen (1987. J. Chromatography. 397:279-285), we find that T beta 4 is an abundant peptide in these cells. By reverse phase HPLC of perchloric acid supernatants, human PMNs contain approximately 169 fg/cell +/- 90 fg/cell (SD), corresponding to a cytoplasmic concentration of approximately 149 +/- 80.5 microM. On non-denaturing polyacrylamide gels, a large fraction of G-actin in supernatants prepared from resting PMNs has a mobility similar to the G-actin/T beta 4 complex. Chemoattractant stimulation of PMNs results in a decrease in this G-actin/T beta 4 complex. To determine whether chemoattractant induced actin polymerization results from an inactivation of T beta 4, the G-actin sequestering activity of supernatants prepared from resting and chemoattractant stimulated cells was measured by comparing the rates of pyrenyl-actin polymerization from filament pointed ends. Pyrenyl actin polymerization was inhibited to a greater extent in supernatants from stimulated cells and these results are qualitatively consistent with T beta 4 being released as G-actin polymerizes, with no chemoattractant induced change in its affinity for G-actin. The kinetics of bovine spleen T beta 4 binding to muscle pyrenyl G-actin are sufficiently rapid to accommodate the rapid changes in actin polymerization and depolymerization observed in vivo in response to chemoattractant addition and removal. PMID- 1447301 TI - Okadaic acid induces interphase to mitotic-like microtubule dynamic instability by inactivating rescue. AB - We used high-resolution video microscopy to visualize microtubule dynamic instability in extracts of interphase sea urchin eggs and to analyze the changes that occur upon addition of 0.8-2.5 microM okadaic acid, an inhibitor of phosphatase 1 and 2A (PP1, PP2a) (Bialojan, D., and A. Takai. 1988. Biochem. J. 256:283-290). Microtubule plus-ends in these extracts oscillated between the elongation and shortening phases of dynamic instability at frequencies typical for interphase cells. Switching from elongation to shortening (catastrophe) was frequent, but microtubules persisted and grew long because of frequent switching back to elongation (rescue). Addition of okadaic acid to the extract induced rapid (< 5 min) conversion to short, dynamic microtubules typical of mitosis. The frequency of catastrophe doubled and the velocities of elongation and shortening increased slightly; however, the major change was an elimination of rescue. Thus, modulation of the rescue frequency by phosphorylation-dependent mechanisms may be a major regulatory pathway for selectively controlling microtubule dynamics without dramatically changing velocities of microtubule elongation and shortening. PMID- 1447302 TI - Physiological evidence for involvement of a kinesin-related protein during anaphase spindle elongation in diatom central spindles. AB - We have developed a new model system for studying spindle elongation in vitro using the pennate, marine diatom Cylindrotheca fusiformis. C. fusiformis can be grown in bulk to high densities while in log phase growth and synchronized by a simple light/dark regime. Isolated spindles can be attained in quantities sufficient for biochemical analysis and spindle tubulin is approximately 5% of the total protein present. The spindle isolation procedure results in a 10-fold enrichment of diatom tubulin and a calculated 40-fold increase in spindle protein. Isolated spindles or spindles in permeabilized cells can elongate in vitro by the same mechanism and with the same pharmacological sensitivities as described for other anaphase B models (Cande and McDonald, 1986; Masuda et al., 1990). Using this model, in vitro spindle elongation rate profiles were developed for a battery of nucleotide triphosphates and ATP analogs. The relative rates of spindle elongation produced by various nucleotide triphosphates parallel relative rates seen for kinesin-based motility in microtubule gliding assays. Likewise ATP analogs that allow discrimination between myosin-, dynein-, and kinesin-mediated motility produce relative spindle elongation rates characteristic of kinesin motility. Also, isolated spindle fractions are enriched for a kinesin related protein as identified by a peptide antibody against a conserved region of the kinesin superfamily. These data suggest that kinesin-like motility contributes to spindle elongation during anaphase B of mitosis. PMID- 1447303 TI - Kinesin family in murine central nervous system. AB - In neuronal axons, various kinds of membranous components are transported along microtubules bidirectionally. However, only two kinds of mechanochemical motor proteins, kinesin and brain dynein, had been identified as transporters of membranous organelles in mammalian neurons. Recently, a series of genes that encode proteins closely related to kinesin heavy chain were identified in several organisms including Schizosaccharomyces pombe, Aspergillus niddulans, Saccharomyces cerevisiae, Caenorhabditus elegans, and Drosophila. Most of these members of the kinesin family are implicated in mechanisms of mitosis or meiosis. To address the mechanism of intracellular organelle transport at a molecular level, we have cloned and characterized five different members (KIF1-5), that encode the microtubule-associated motor domain homologous to kinesin heavy chain, in murine brain tissue. Homology analysis of amino acid sequence indicated that KIF1 and KIF5 are murine counterparts of unc104 and kinesin heavy chain, respectively, while KIF2, KIF3, and KIF4 are as yet unidentified new species. Complete amino acid sequence of KIF3 revealed that KIF3 consists of NH2-terminal motor domain, central alpha-helical rod domain, and COOH-terminal globular domain. Complete amino acid sequence of KIF2 revealed that KIF2 consists of NH2 terminal globular domain, central motor domain, and COOH-terminal alpha-helical rod domain. This is the first identification of the kinesin-related protein which has its motor domain at the central part in its primary structure. Northern blot analysis revealed that KIF1, KIF3, and KIF5 are expressed almost exclusively in murine brain, whereas KIF2 and KIF4 are expressed in brain as well as in other tissues. All these members of the kinesin family are expressed in the same type of neurons, and thus each one of them may transport its specific organelle in the murine central nervous system. PMID- 1447304 TI - Tyrosine phosphorylation of membrane proteins mediates cellular invasion by transformed cells. AB - Tyrosine phosphorylation of membrane-associated proteins is involved at two distinct sites of contact between cells and the extracellular matrix: adhesion plaques (cell adhesion and de-adhesion) and invadopodia (invasion into the extracellular matrix). Adhesion plaques from chicken embryonic fibroblasts or from cells transformed by Rous sarcoma virus contain low levels of tyrosine phosphorylated proteins (YPPs) which were below the level of detection in 0.5 microns thin, frozen sections. In contrast, intense localization of YPPs was observed at invadopodia of transformed cells at sites of degradation and invasion into the fibronectin-coated gelatin substratum, but not in membrane extensions free of contact with the extracellular matrix. Local extracellular matrix degradation and formation of invadopodia were blocked by genistein, an inhibitor of tyrosine-specific kinases, but cells remained attached to the substratum and retained their free-membrane extensions. Invadopodia reduced or lost YPP labeling after treatment of the cells with genistein, but adhesion plaques retained YPP labeling. The plasma membrane contact fractions of normal and transformed cells have been isolated form cells grown on gelatin cross-linked substratum using a novel fractionation scheme, and analyzed by immunoblotting. Four major YPPs (150, 130, 81, and 77 kD) characterize invadopodial membranes in contact with the matrix, and are probably responsible for the intense YPP labeling associated with invadopodia extending into sites of matrix degradation. YPP150 may be an invadopodal-specific YPP since it is approximately 3.6-fold enriched in the invasive contact fraction relative to the cell body fraction and is not observed in normal contacts. YPP130 is enriched in transformed cell contacts but may also be present in normal contacts. The two major YPPs of normal contacts (130 and 71 kD) are much lower in abundance than the major tyrosine-phosphorylated bands associated with invadopodial membranes, and likely represent major adhesion plaque YPPs. YPP150, paxillin, and tensin appear to be enriched in the cell contact fractions containing adhesion plaques and invadopodia relative to the cell body fraction, but are also present in the soluble supernate fraction. However, vinculin, talin, and alpha-actinin that are localized at invadopodia, are equally concentrated in cell bodies and cell contacts as is the membrane adhesion receptor beta 1 integrin. Thus, tyrosine phosphorylation of the membrane bound proteins may contribute to the cytoskeletal and plasma membrane events leading to the formation and function of invadopodia that contact and proteolytically degrade the extracellular matrix; we have identified several candidate YPPs that may participate in the regulation of these processes. PMID- 1447305 TI - Apoptosis in metanephric development. AB - During metanephric development, non-polarized mesenchymal cells are induced to form the epithelial structures of the nephron following interaction with extracellular matrix proteins and factors produced by the inducing tissue, ureteric bud. This induction can occur in a transfilter organ culture system where it can also be produced by heterologous cells such as the embryonic spinal cord. We found that when embryonic mesenchyme was induced in vitro and in vivo, many of the cells surrounding the new epithelium showed morphological evidence of programmed cell death (apoptosis) such as condensed nuclei, fragmented cytoplasm, and cell shrinking. A biochemical correlate of apoptosis is the transcriptional activation of a calcium-sensitive endonuclease. Indeed, DNA isolated from uninduced mesenchyme showed progressive degradation, a process that was prevented by treatment with actinomycin-D or cycloheximide and by buffering intracellular calcium. These results demonstrate that the metanephric mesenchyme is programmed for apoptosis. Incubation of mesenchyme with a heterologous inducer, embryonic spinal cord prevented this DNA degradation. To investigate the mechanism by which inducers prevented apoptosis we tested the effects of protein kinase C modulators on this process. Phorbol esters mimicked the effects of the inducer and staurosporine, an inhibitor of this protein kinase, prevented the effect of the inducer. EGF also prevented DNA degradation but did not lead to differentiation. These results demonstrate that conversion of mesenchyme to epithelial requires at least two steps, rescue of the mesenchyme from apoptosis and induction of differentiation. PMID- 1447307 TI - Similar, but not identical, modulation of expression of extracellular matrix components during in vitro and in vivo aging of human skin fibroblasts. AB - Regulation of the synthesis of procollagen and other extracellular matrix components was examined in human skin fibroblasts obtained from donors of various ages, from fetal to 80 years old (in vivo aged), and in fetal fibroblasts at varying passage levels (in vitro aged). Growth rates and saturation densities of fibroblasts decreased with increasing age of the donor and after passage 20 of fetal fibroblasts. The rates of collagen and proteoglycan synthesis also decreased during both types of aging to about 10-25% of the rate in early passage fetal fibroblasts, whereas the synthesis of total noncollagenous proteins was not greatly affected. Decreased collagen synthesis in both types of aging was correlated with lower steady-state levels of mRNAs for the two subunits of type I procollagen mRNA, although their regulation was not coordinate. Type III collagen mRNA levels also declined in both types of aging. The concentration of fibronectin mRNA also decreased during in vitro aging but more rapidly than the collagen mRNAs, whereas in fibroblasts from 51-80-year-old donors, it was similar to or higher than in early passage fetal fibroblasts. This study suggests that the decreased synthesis of procollagen and proteoglycans in in vivo aged fibroblasts represents changes that are responsible for intrinsic degenerative changes that occur in human skin during aging. Furthermore, although in vitro and in vivo aging were similar in many respects, they were not equivalent, as evidenced by the differences in regulation of fibronectin expression. PMID- 1447306 TI - Minimal DNA sequences that control the cell lineage-specific expression of the pro alpha 2(I) collagen promoter in transgenic mice. AB - The pattern of expression of the pro alpha 2(I) collagen gene is highly tissue specific in adult mice and shows its strongest expression in bones, tendons, and skin. Transgenic mice were generated harboring promoter fragments of the mouse pro alpha 2(I) collagen gene linked to the Escherichia coli beta-galactosidase or firefly luciferase genes to examine the activity of these promoters during development. A region of the mouse pro alpha 2(I) collagen promoter between 2,000 and +54 exhibited a pattern of beta-galactosidase activity during embryonic development that corresponded to the expression pattern of the endogenous pro alpha 2(I) collagen gene as determined by in situ hybridization. A similar pattern of activity was also observed with much smaller promoter fragments containing either 500 or 350 bp of upstream sequence relative to the start of transcription. Embryonic regions expressing high levels of beta-galactosidase activity included the bulbus arteriosus, valves of the developing heart, sclerotomes, meninges, limb buds, connective tissue fascia between muscle fibers, osteoblasts in newly formed bones, fibroblasts in tendons, periosteum, dermis, and peritoneal membranes. The pattern of beta-galactosidase activity was similar and included within the extracellular immunohistochemical localization pattern of transforming growth factor-beta 1 (TGF-beta 1). The -315(-)-284 region of the pro alpha 2(I) collagen promoter was previously shown to mediate the stimulatory effects of TGF-beta 1 on the pro alpha 2(I) collagen promoter in DNA transfection experiments with cultured fibroblasts. A construct containing this sequence tandemly repeated 5' to a very short alpha 2(I) collagen promoter (-40(-)+54) showed preferential activity in tail and skin of 4-wk-old transgenic mice. Except for low expression of the transgene in bone, this pattern mimics the expression of the endogenous pro alpha 2(I) collagen gene. We propose the hypothesis that the tissue-specific expression of the pro alpha 2(I) collagen gene during embryogenesis is controlled by both TGF-beta 1 and cell-specific transcription factors; one of these could interact directly or indirectly with either the -315( )-284 or the -40(-)+54 segment. PMID- 1447308 TI - Tributyltin is a potent inducer of the heat shock response in human diploid fibroblasts. AB - Submicromolar concentrations of tributyltin (TBT), a commercially used organotin compound, were found to induce the expression of several stress proteins, most notably HSP89 and HSP70, in IMR-90 human diploid fibroblasts in a time- and dose dependent manner. This induction can be demonstrated by quantitation of 1) synthesis of the heat shock proteins (HSPs), 2) relative abundance of mRNA of hsp70, and 3) transient expression of a human hsp70 promoter driven reporter gene. TBT also increased the abundance of mRNA of heme oxygenase, whereas heat shock was without effect. Analysis of protein binding to a consensus heat shock element (HSE) by electrophoretic mobility shift assay suggests that the induction of the heat shock response by TBT was attributable to activation of the heat shock transcription factor (HSTF). PMID- 1447309 TI - Localization of p35 (annexin I, lipocortin I) in normal adult rat kidney and during recovery from ischemia. AB - The 35-kDa protein (p35, lipocortin I, annexin I), originally discovered as a Ca(++)-dependent substrate for the EGF receptor tyrosine kinase, binds Ca++ and phospholipids, is developmentally regulated in embryos and has restricted expression in adults. Immunohistochemistry of normal rat kidney shows that p35 is enriched in epithelia of Bowman's capsule, the macula densa, and medullary/papillary collecting ducts, suggesting that p35 is related to specialized renal functions. Light staining is observed in the thick ascending limb; elsewhere, immunoreactivity is nil. Since renal recovery from ischemia involves both hyperplasia and hypertrophy and reportedly is accelerated by EGF, we examined p35 distribution during this process. After 48 hours of recovery, both the distribution and amount of renal p35 are altered. Immunoblots show p35 levels increased at least threefold in whole-kidney homogenates. The expression of p35 is still highly restricted in recovering kidneys; however, the thick ascending limb now stains heavily. This is the first documentation of alterations in annexin levels during a pathophysiologic response. However, our attempts to discern effects of exogenous EGF on the recovery from ischemia were negative for both mitotic index and renal function assays. PMID- 1447310 TI - Lactoferrin binding sites and nuclear localization in K562(S) cells. AB - Lactoferrin, a single chain cationic glycoprotein, present in the secondary granules of neutrophils, acts as a negative feedback regulator of myelopoiesis. Specific receptors for lactoferrin were detected on the surface of different hematopoietic cell types. The influence of lactoferrin on cell growth in culture has been reported. Interactions of lactoferrin with DNA were also demonstrated. In the present paper we confirm the presence of lactoferrin specific binding sites on K562 cells and we estimate the number of binding sites and the dissociation constant. By Western blotting analysis performed on K562 lysates we find a band of about 120 kDa responsible for specific binding of lactoferrin. We also show that lactoferrin, after binding at the cell surface, is internalized in a temperature dependent way and is immunologically detectable as a DNA-linked protein in nuclear extracts. PMID- 1447311 TI - Biphasic effect of the mitotoxin bFGF-saporin on bovine lens epithelial cell growth: effect of cell density and extracellular matrix. AB - We have studied the effect of a specific FGF receptor suicide antagonist on the growth of bovine epithelial cells (BEL cells) in culture. This basic fibroblast growth factor-saporin conjugate (bFGF-SAP) has a biphasic effect on bovine lens epithelial cells (BEL cells). Whereas 0.01 nM and 0.1 nM bFGF-SAP stimulate BEL cells proliferation, 1 nM and 10 nM bFGF-SAP have the predicted toxic effects on BEL cell growth. The toxicity of bFGF-SAP is observed 2 to 3 days after the initial treatment and depends on cell density. Accordingly, the sensitivity of confluent cells to bFGF-SAP is reduced compared to sparse cells. A time course analysis reveals that bFGF-SAP is effective after a short exposure to cells and that its effects are not increased with longer treatments. Cell growth on bFGF SAP pretreated extracellular matrix (ECM) or posterior lens capsule (PLC) is also affected. Basic FGF-SAP has been shown to bind to the extracellular material, allowing a modulation of lens cells migration and survival by a single treatment in vitro. This finding raises the possibility of its use in vivo to prevent capsules invasion by lens cells after cataract surgery. PMID- 1447312 TI - Cortical photons in early development of frog eggs: comparative study of photon emission between nuclear division and cytoplasmic fission. AB - In the study of cell division in the early development of frog eggs, cortical photon emission was investigated by converting small light emission from living cells into digital pulses of potentials and recording the integrals of these pulses (analog method), counting the number of pulses (photon-counting method), and counting the number of integrated pulses (improved photon-counting method). By the analog and improved photon-counting methods, changes in photon emission due to cell division could be clearly detected. The emitted light increased about 5.10(-19)W at the start of a cleavage furrow. Rapid changes in chemical reactions causing photon emission were compared during nuclear division and cytoplasmic phases. This emission occurred mainly in cytoplasmic fission, the rate being greater than in nuclear division by a factor of about 2.9. Chemical reaction rates were shown to differ according to bulk emission, thus indicating the mechanisms for the reactions to also differ. PMID- 1447313 TI - Interferon-gamma inhibits proliferation, but not commitment, of murine granulocyte-macrophage progenitors. AB - We investigated the effects of interferon gamma (IFN-gamma) on the growth of murine hematopoietic progenitors. IFN-gamma inhibited granulocyte colony stimulating factor (G-CSF)- and interleukin-3 (IL-3)-dependent colony growth by granulocyte-macrophage (GM) progenitors derived from the bone marrow cells of normal mice. However, the number of IL-3-dependent GM colonies formed by the bone marrow cells of 5-fluorouracil (5-FU)-treated mice was not influenced by the addition of IFN-gamma. Replating experiments suggested that IFN-gamma suppressed GM colony growth directly and that it exerted an inhibitory effect on the proliferation, but not on the commitment, of GM progenitors. In contrast, IFN gamma failed to suppress colony growth by mast cell progenitors. Erythroid and megakaryocytic progenitors exhibited different responses to IFN-gamma depending on mouse strains. These results suggest that potent negative regulators are not always inhibitors of hematopoietic progenitors. PMID- 1447314 TI - Electrochemical potentials of potassium in skeletal muscle under different metabolic states. AB - Intracellular potassium and membrane potential were measured simultaneously by means of double-barrelled liquid ion-exchange microelectrodes in single fibers of rat thigh muscle in vivo in rats maintained in seven different metabolic states. The K+ equilibrium potential (EK) was more negative than the simultaneously measured membrane potential (Em) in the normal state by 18.4 mV. K+ loading, acute and chronic, resulted in depolarization of Em due to increased serum K+ (hyperkalemia) with no increase in intracellular K+. K+ depletion resulted in hyperpolarization of Em as plasma K+ decreased proportionately more than intracellular K+. Low Na+ diet had no effect. Intracellular K+ was decreased in acute acidosis but not in the chronic state. Thus K+ depletion and acute acidosis are associated with intracellular K+ decrease. The fact that hyperpolarization exists in the former and not the latter is a reflection that hypokalemia accompanies the former condition. The hyperpolarizing states of K+ depletion and chronic acidosis are accompanied by decreased excitability and muscle weakness. PMID- 1447315 TI - In vitro effect of extracellular AMP on MCF-7 breast cancer cells: inhibition of glycolysis and cell proliferation. AB - MCF-7 human breast cancer cells propagated in vitro were treated with adenosine derivatives added to the culture medium. The effects on cell proliferation, glycolysis, and glutaminolysis were investigated. Of all adenosine derivatives tested, AMP was the most efficient inhibitor of cell proliferation. In AMP treated cells, DNA synthesis decreased, whereas RNA and protein syntheses rose normally with time. In terms of carbohydrate metabolism, lactate production from glucose was drastically reduced; therefore, most of lactate produced must have been derived from glutamine. Increases in the enzyme activities involved in glutamate degradation and in the malate-aspartate shuttle were observed. In contrast, actual glycolytic flux rates declined, whereas key glycolytic enzyme activities increased. Metabolites such as fructose 1,6-bisphosphate and pyruvate accumulated in AMP-arrested cells. Based on the lowered NAD level in the AMP treated cells, lactate dehydrogenase, but not malate dehydrogenase, was impaired; thereby the whole of glycolysis was inhibited. In compensation, glutamine catabolism was increased. NAD concentrations fell drastically because of the known inhibition of P-ribose-PP synthesis through heightened intracellular AMP levels. A hypothetical metabolic scheme to explain these results and to show how extracellular AMP may influence carbohydrate metabolism and cell proliferation is presented. PMID- 1447316 TI - Inhibition of apoptosis in human tumour cells by okadaic acid. AB - Gamma-radiation, tetrandrine, bistratene A, and cisplatin were all found to induce pronounced morphological changes characteristic of apoptosis and extensive DNA fragmentation in the human BM13674 cell line 8 h after treatment. Apoptosis induced in BM13674 cells by these diverse agents was markedly inhibited by 1 microM okadaic acid, a tumour promoter that inhibits protein phosphatases 1 and 2A. This compound also inhibited the appearance of apoptosis in fresh human leukaemia cells that had been exposed to gamma-radiation. The inhibition of apoptosis was confirmed using fluorescence microscopy and DNA gel electrophoresis. Dephosphorylation of a limited number of proteins was shown to be associated with apoptosis and okadaic acid prevented these dephosphorylations. Previous studies on the BM13674 cell line showed that an inhibitor of protein synthesis failed to prevent apoptosis in these cells. The present data provides further support that posttranslational modification of proteins, in particular, phosphorylation/dephosphorylation status, plays an important role in inhibition/activation of programmed cell death in different human cells after exposure to several cytotoxic agents. PMID- 1447317 TI - Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. AB - Vascular endothelial growth factor (VEGF) is a 45kDa secreted peptide that has potent mitogenic activity specific for endothelial cells in vitro and the ability to induce a strong angiogenic response in vivo. In the present study, 24 h treatment with VEGF resulted in a stimulation of expression of the metalloproteinase, interstitial collagenase, at the protein and mRNA levels 2.5 3.0-fold in human umbilical vein endothelial cells but not in human dermal fibroblasts. The dose response curve for collagenase induction was biphasic with the peak stimulatory response obtained by treatment of cells with 10-100 ng/ml (0.2-2 nM) VEGF. The dose response curve for collagenase induction overlapped with, but was not identical to, the response curve for proliferation, which showed VEGF mitogenic activity between < or = 0.1-50 ng/ml (< or = 0.002-1 nM). There was no induction seen in expression of other members of the matrix metalloproteinase family, including the 72kDa type IV collagenase, the 92kDa type V collagenase, or stromelysin. Expression of transcripts for the major metalloproteinase inhibitor, tissue inhibitor of metalloproteinases, was also unaltered by treatment with VEGF (1-200 ng/ml). These studies demonstrate that in addition to stimulating proliferation of endothelial cells, VEGF can also induce the expression of the only metalloproteinase that can initiate degradation of interstitial collagen types I-III under normal physiological conditions. Both responses are likely to contribute to the angiogenic potential of this peptide. PMID- 1447318 TI - Partial characterization of skeletal myoblast mitogens in mouse crushed muscle extract. AB - We have utilized a model system to investigate myotrophic factors released by normal adult mouse muscles following a crush injury. We found that saline extracts from gently crushed mouse muscles (CME) contain potent mitogenic activities which act on primary newborn mouse myoblast cultures, as well as on mouse C2 cells, a mouse myoblast cell line. We compared the activity of CME on mouse myoblasts with that of basic fibroblast growth factor (bFGF) and insulin like growth factor I (IGF-I), two growth factors known to be mitogenic for primary myoblasts (Allen, Dodson, and Lutein: Exp. Cell. Res., 152:154-160, 1984; DiMario and Strohman: Differentiation, 39:42-49, 1988; Allen and Boxhorn: J. Cell. Physiol., 138:311-315, 1989; Dodson, Allen, and Hossner: Endocrinology, 117:2357-2363, 1985; Florini and Magri: Am. J. Physiol., 256:C701-C711, 1989). We found that CME could act in an additive fashion to saturating doses of bFGF to increase proliferation in myoblast cultures. Additionally, CME acted additively to the combination of saturating amounts of bFGF and IGF-I on both C2 and primary myoblast cultures. We also examined additivity of CME with the combination of saturating doses of bFGF, IGF-I, transferrin (Tf), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), adrenocorticotrophin (ACTH), and macrophage colony-stimulating factor (M-CSF). Our data indicate that CME contains Tf, as well as one or more uncharacterized mitogens for myoblasts which are distinct from Tf, the IGFs, bFGF, EGF, PDGF, M-CSF, and ACTH. These uncharacterized mitogens may act independently of known growth factors to stimulate myoblast proliferation, or may act through modulation of known growth factor activities. PMID- 1447319 TI - Effect of membrane phosphatidylethanolamine-deficiency/phosphatidylcholine-excess on the metabolism of phosphatidylcholine and phosphatidylethanolamine. AB - Cells of epithelial origin generally require ethanolamine (Etn) to grow in defined culture medium. When such cells are grown without Etn, the membrane phospholipid composition changes drastically, becoming phosphatidylethanolamine (PE)-deficient due to a reduced de novo rate of PE synthesis, and growth stops. We have hypothesized that the cessation of growth occurs because this membrane phospholipid environment is no longer suitable for membrane-associated functions. Phospholipid has long been known to play a role in the transduction of some signals across membranes. In addition to the well-known phosphatidylinositol cycles, hydrolysis of phosphatidylcholine (PC) and PE has recently been shown to play a central role in signal transduction. Using an Etn-requiring rat mammary cell line 64-24, we have studied the metabolism of PC and PE in response to the phorbol ester phorbol 12,13-dibutyrate (PDBu) under conditions where cells have either normal or PE-deficient membrane phospholipid. In cells having normal membrane phospholipid, the synthesis of PC was stimulated by PDBu (approximately fourfold), as was the degradation of PC and PE (by twofold and fourfold, respectively). Product analysis suggested that PDBu stimulated hydrolysis of PC by both phospholipases C and D (PLC and PLD), and of PE by PLD. However, in PE deficient cells, neither lipid synthesis or degradation were significantly stimulated by PDBu. Analysis of the CDP-choline pathway of PC synthesis indicated that the regulatory enzyme, CTP:phosphorylcholine cytidylyltransferase, was stimulated about twofold by PDBu in cells having normal membrane, but not in PE deficient cells. These results indicate that the membrane phospholipid environment profoundly affects phospholipid metabolism, which no doubt influences cell growth and regulation. PMID- 1447320 TI - Transforming growth factor-beta 1 (TGF-beta 1) up-regulation of collagen type II in primary cultures of rabbit articular chondrocytes (RAC) involves increased mRNA levels without affecting mRNA stability and procollagen processing. AB - The effect of transforming growth factor-beta 1 (TGF-beta 1) on collagen biosynthesis was investigated in confluent primary monolayer cultures of rabbit articular chondrocytes (RAC). Exposure to TGF-beta (0.1, 1, and 10 ng/ml) in serum-free medium caused a dose- and time-dependent stimulation of collagen biosynthesis associated with an increase of steady-state levels of procollagen type II mRNA. Elevation of the mRNA steady-state did not result from a stabilization of the transcript, as shown by measure of the mRNA half-life. Electrophoresis (SDS-PAGE) showed that TGF-beta stimulates the synthesis of most collagen isotypes, including type II, without qualitative change in their distribution. Moreover, pulse-chase experiments revealed that TGF-beta did not affect the processing rate of type II procollagen. TGF-beta slightly stimulated the production of prostaglandin E2 (PGE2), which could in turn exert an inhibition on collagen synthesis. However, addition of indomethacin to block prostaglandin synthesis did not further enhance the TGF-beta-induced stimulation of collagen production, suggesting that this mediator was not implicated in the effect. Moreover, TGF-beta increased steady-state levels of procollagen type II, I, and III mRNAs even in the presence of indomethacin. Despite these increased mRNA levels, only the production of type II collagen was significantly augmented, suggesting that type I procollagen mRNA was not fully translated. In addition, the TGF-beta-induced stimulation of collagen synthesis was observed whenever ascorbic acid is added or not in the culture medium. In conclusion, TGF-beta, which is present in great amount in bone and cartilage, can increase the collagen production of cultured RAC and might therefore play a role in the early events of cartilage repair, such as those observed in osteoarthritis. PMID- 1447321 TI - Nonreceptor mediated nuclear accumulation of insulin in H35 rat hepatoma cells. AB - We previously demonstrated that insulin accumulated in the nucleus in several cell types and partially characterized the uptake mechanisms and pathways in H35 rat hepatoma cells. Nuclear accumulation of insulin was energy independent, time, temperature, and insulin concentration dependent, but apparently nonsaturable. This study investigated further the initial endocytotic pathways that contribute to the nuclear accumulation of insulin using trypsin treatment of the cells to prevent insulin binding to its plasma membrane receptor. Total cell-associated, intracellular, and nuclear insulin were compared in control and trypsin-treated H35 hepatoma cells. Trypsin treatment markedly decreased total cell-associated and intracellular insulin as well as the nuclear accumulation of insulin when cells were incubated with 2.8 ng/ml insulin. When the cells were incubated with 100 ng/ml insulin, trypsin treatment totally inhibited insulin binding to the plasma membrane for at least 90 min. However, intracellular accumulation of insulin was reduced by only 50% at 60 min, and trypsin treatment failed to inhibit the nuclear accumulation of insulin. Chemical extraction and Sephadex G 50 chromatography revealed nuclear associated insulin in trypsin-treated cells was identical to that in control cells incubated with either 2.8 or 100 ng/ml insulin. These results suggest that a nonreceptor mediated uptake pathway, i.e., fluid-phase endocytosis, contributed significantly to the nuclear accumulation of insulin at high insulin concentrations, but at lower insulin concentrations the receptor-mediated pathway predominated. No matter which initial endocytotic route was used to internalize insulin, the insulin apparently associated with the same nuclear matrix proteins. This association of insulin with the nuclear matrix may be involved in regulation of nuclear events such as cell growth and differentiation or gene transcription. PMID- 1447322 TI - Alterations in cellular calcium handling as a result of systemic calcium deficiency in the developing chick embryo: I. Erythrocytes. AB - Chick embryos rendered calcium (Ca) deficient by shell-less (SL) culture develop hypertension and tachycardia. Since hypocalcemia is accompanied by hypernatremia systemically but not by lower cellular Ca (Koide and Tuan, 1989), we speculate that cellular Ca handling may be altered in the SL embryo, perhaps involving Na transport. Using erythrocytes (RBC) from day-14 SL and normal (NL) embryos as the experimental cell, cellular Ca handling was studied under varying extracellular osmotic and ionic conditions by analyzing 45Ca uptake and cell volume regulation. Two agents, p-chloromercuriphenylsulfonate (PCM), and inosine/iodoacetamide (INI) were used to treat the RBCs to modify plasma membrane ion permeability and to deplete cellular ATP, respectively. Other cellular functions and activities related to Ca homeostasis, including ATP content and Ca(2+)-ATPase activity, were also analyzed. These analyses showed: (1) in NaCl, Ca uptake was similar in NL and SL cells, except after INI treatment, which resulted in slower Ca uptake by the SL cells, (2) in choline and sucrose, Ca uptake by SL RBCs was higher, (3) Ca uptake by RBCs of both embryos changed depending on the osmotic agent (Na < K < or = choline < sucrose), (4) Ca(2+)-ATPase activity was higher in SL RBC, although there was no change in the size or charge of the enzyme, and (5) in any osmotic agent, cellular Na was significantly lower, whereas cellular K was higher, in SL RBC. Based on these results, three features of RBC Ca handling were apparent: (1) Na-Ca exchange was functional and was more active in SL RBCs, (2) Ca uptake was dependent on the total ionic electrochemical gradient but not on bulk H2O movement, and (3) Ca pumping out capacity was directly correlated with Ca(2+)-ATPase activity. Elevated Ca uptake in sucrose-treated SL RBC is therefore indicative of its greater ion permeability. Taken together, these findings indicate that cellular Ca handling of the RBCs of SL chick embryos is characterized by a more active Na-Ca exchange system, greater ion permeability, and higher Ca pumping out capacity, thereby suggesting an up-regulated Ca handling function in the SL RBCs. The abnormal cellular Ca handling may be a direct result of the systemic Ca deficiency of the SL chick embryo and may be functionally related to its hypertension and tachycardia. PMID- 1447324 TI - An assertiveness training program for a group of elders. PMID- 1447323 TI - Alterations in cellular calcium handling as a result of systemic calcium deficiency in the developing chick embryo: II. Ventricular myocytes. AB - We have previously shown that cardiovascular anomalies, such as hypertension and tachycardia, develop in Ca(2+)-deficient, shell-less (SL) chick embryos cultured ex ovo, accompanied by elevated circulating catecholamines and higher alpha adrenergic sensitivity of cardiovascular functions. Results described in the preceding work, using erythrocytes as an experimental system, show that cellular Ca2+ handling properties are also altered as a result of long-term calcium deficiency. To examine the relevance of these findings to cells of the cardiovasculature, we have analyzed and compared the Ca2+ handling characteristics of the heart cells of SL and normal (NL) embryos. For this study, isolated and cultured ventricular myocytes of SL and NL embryos were loaded with Fura-2 via transient membrane damage with glass beads. Compared to Fura-2/AM, bead loading yielded similar values and kinetic profiles of [Ca2+]i-dependent differential fluorescence and, in addition, did not affect cell viability and beating activity. The Fura-2 loaded ventricular myocytes were washed in Ca(2+) free buffer and then analyzed by ratiometric fluorescence (350 nm/380 nm) microscopy for kinetic changes in [Ca2+]i (R350/380 values) as a function of [Ca2+]o and adrenergic modifiers. At 0.5 and 1.0 mM [Ca2+]o, SL cells showed significantly higher [Ca2+]i, higher beating rates, and faster rate of increase in [Ca2+]i compared to NL cells. At higher [Ca2+]o (3.5 mM), there was no significant difference in [Ca2+]i and beating rate between NL and SL cells. Treatment with norepinephrine (NE; 0.01-1 microM) at 1 mM [Ca2+]o substantially increased [Ca2+]i in both NL and SL cells. In the former, the NE effect was completely inhibited by beta-blockade (1 microM propranolol). In contrast, in SL cells, NE remained effective after beta-blockade, and combined alpha-blockade (1 microM prazosin) and beta-blockade was needed to inhibit completely the NE effect. In both NL and SL cells, treatment with NE substantially increased beating rates in a similar manner. Taken together, these findings suggest that Ca2+ handling and adrenergic regulation of the heart cells are significantly altered in the SL embryos, and that these alterations may be related to the development of impaired cardiovascular functions resulting from systemic Ca2+ deficiency. PMID- 1447325 TI - Personhood: a theory for gerontological nursing. PMID- 1447326 TI - Near-death experiences and the elderly. PMID- 1447327 TI - Spirituality and aging. PMID- 1447328 TI - The senior's therapeutic touch education program. PMID- 1447329 TI - Wellness for elders. PMID- 1447330 TI - Influencing holistic nursing practice in long-term care. PMID- 1447332 TI - The elderly as caregivers of the elderly. PMID- 1447331 TI - Community issues in the holistic care of the elderly. PMID- 1447333 TI - Integrality as a holistic framework for the life-review process. PMID- 1447334 TI - A gerontological nursing issue: the aged developmentally disabled/mentally retarded. PMID- 1447335 TI - Application of triple quadrupole tandem mass spectrometry to the analysis of pyridine-containing derivatives of long-chain acids and alcohols. AB - An improved derivatization procedure for the preparation of nicotinate and 3 picolinyl esters from mixtures of fatty alcohols and acids has been developed. The derivatives can be analysed by capillary gas chromatography on an SE-54 type column, which affords separation of the acid and alcohol derivatives with the same carbon chain. Detection with tandem mass spectrometric techniques on a triple quadrupole instrument is feasible, and yields informative spectra devoid of coeluting interferences. PMID- 1447336 TI - Simultaneous analysis of azidothymidine and its mono-, di- and triphosphate derivatives in biological fluids, tissue and cultured cells by a rapid high performance liquid chromatographic method. AB - A rapid high-performance liquid chromatographic (HPLC) method for the simultaneous analysis of the antiviral drug azidothymidine (AZT), AZT monophosphate, AZT diphosphate and AZT triphosphate, with ultraviolet detection in the nanomolar range, is described. Determination of these compounds in vitro in the human MT-4 lymphocyte cell line did not require a prior extraction, and AZT and its phosphorylated derivatives could be accurately analysed in one HPLC run. However, plasma, bile, liver homogenate and urine samples could not be injected directly into the chromatograph. Therefore, a solid-phase extraction procedure was developed, using azidodideoxyinosine as internal standard. The extractions of the compounds of interest from all but urine samples were reproducible, with recoveries between 65% (AZT triphosphate from plasma) and 100% (AZT from plasma). PMID- 1447337 TI - High-performance liquid chromatographic methods for the determination of the penems SCH 29482 and FCE 22101 in human serum and urine. AB - High-performance liquid chromatographic methods have been developed for the determination of two 6-(1-hydroxyethyl)penems, SCH 29482 (I) and FCE 22101 (II), in serum and urine. Serum samples were combined with an equal volume of methanol to remove proteins and, after centrifugation, an aliquot of the supernatant was analysed by ion-pair chromatography on a reversed-phase C18 column with hexadecyltrimethylammonium bromide as the ion-pairing agent. The compounds were detected by their ultraviolet absorbance at 305 nm for II and 322 nm for I. Urine samples were diluted, filtered and analysed by the same chromatographic procedure. At concentrations of 1-500 micrograms/ml of each compound, the within- and between-day precisions were 1.8-3.6 and 2.6-5.1%, respectively. The detection limit was 0.2 micrograms/ml for I and 0.3 micrograms/ml for II. PMID- 1447338 TI - High-performance liquid chromatographic determination of pamaquine, primaquine and carboxy primaquine in calf plasma using electrochemical detection. AB - A high-performance liquid chromatographic method with electrochemical detection is described for quantification of pamaquine, primaquine and carboxy primaquine in calf plasma. After the proteins had been precipitated with acetonitrile, the drugs were separated on a 5-microns C18-modified polymer gel column with an isocratic mobile phase. The detection limit was 0.01 microgram/ml in plasma for all three compounds. The applicability of the method in pharmacokinetic studies was demonstrated by determining the plasma concentrations of the three substances in calves administered a single dose of pamaquine or primaquine. PMID- 1447339 TI - Gas chromatographic profiles of plasma total lipids as indicators of dietary history. Correlation with carbohydrate and alcohol intake based on 24-h dietary recall. AB - Quantitative gas chromatographic estimates of the major lipid classes and molecular species in fasting plasma were correlated with total carbohydrate, starch, fibre, sucrose and alcohol intake based on 24-h dietary recall. Spearman coefficients (rs) and tests of significance (P) were obtained for groups of 775 males and 471 females aged 20-59 years from a Toronto-McMaster Lipid Research Clinics Population Study. The most significant correlations varying from rs 0.1 to 0.2 and P 0.001 to 0.0005 (n = 400-773) were between increased intake of alcohol and increased ratios of C50/C54 triacylglycerols, C34/C36 phosphatidylcholines and phosphatidylcholine/free cholesterol (PC/FC) of plasma. Increase in total dietary carbohydrate, starch and fibre correlated with decreasing C50/C54 triacylglycerol, C34/C36 phosphatidylcholine and PC/FC ratios (rs = -0.1-0.2; P less than 0.002-0.04; n = 400-773). In contrast, consumption of high levels of alcohol was associated with increasing C50/C54 triacylglycerol, C34/C36 phosphatidylcholine and PC/FC ratios. A high intake of alcohol (50-150 ml per day) distinguished itself from other simple carbohydrate-induced lipid profiles by its marked effect on increased C50/C52 triacylglycerol and PC/FC ratio. PMID- 1447340 TI - Direct-gradient high-performance liquid chromatographic analysis and preliminary pharmacokinetics of flumequine and flumequine acyl glucuronide in humans: effect of probenecid. AB - A gradient high-performance liquid chromatographic analysis for the direct measurement of flumequine, with its acyl glucuronide, in plasma and urine of humans has been developed. In order to prevent hydrolysis and isomerization of flumequine acyl glucuronide, the samples were acidified by the oral intake of four 1.2-g amounts of ammonium chloride per day. In contrast to the acyl glucuronides of non-steroidal anti-inflammatory drugs, flumequine and its acyl glucuronide were stable in urine of pH 5.0-8.0. Flumequine acyl glucuronide is unstable at pH 1.5. In acidic urine (pH 5-6), almost no flumequine is excreted unchanged (1%): it is excreted chiefly as acyl glucuronide (84.2%). Probenecid co medication reduces the renal excretion rate of flumequine acyl glucuronide from 662 to 447 micrograms/min (p = 0.00080), but not the percentage of glucuronidation. PMID- 1447341 TI - Elution mode of Pneumocystis carinii cysts in gravitational field-flow fractionation. AB - The simplest field-flow fractionation technique, i.e. gravitational, was used in an attempt to purify a Pneumocystis carinii cyst suspension. This parasite is an opportunistic invader in immunocompromised patients, especially those suffering from AIDS. The cyst stage is spherical and 5 microns in diameter. Unexpected retention times, not systematically related to the size and the density of the parasite, were obtained under various experimental conditions. When silicone coated walls were used, Pneumocystis carinii cysts were eluted in the void volume, whereas when uncoated walls were used with a sodium dodecyl sulphate enriched carrier phase, retention was observed. These phenomena are probably related to the high degree of hydrophobicity of these micrometre-sized biological particles; this degree can be easily determined. The use of the gravitational field-flow fractionation technique can be of a great interest for the development of new methods for diagnostic purposes. Particle-wall interactions and their modifications due to the carrier phase or to the wall treatment can be employed in the search for new bronchoalveolar lavage solutions. PMID- 1447342 TI - Determination of methacrylonitrile in serum using gas chromatography and flame ionization detection. AB - A gas chromatographic method is described for the quantitation of methacrylonitrile in serum. Methacrylonitrile was extracted from rat serum with diethyl ether and then quantified using a gas chromatograph equipped with a flame ionization detector and a 60-m megabore column coated with polyethylene glycol polymer. The recoveries obtained following a one-step extraction with diethyl ether varied from 60% at 3.2 micrograms/ml to 70% at 80 micrograms/ml. The coefficient of variation for the analysis ranged from 2.5% at 400 micrograms/ml to 15.0% at 3.2 micrograms/ml. PMID- 1447343 TI - Improved high-performance liquid chromatographic method for the determination of ethylmorphine and its metabolites in microsomal incubations and cell culture media. AB - Ethylmorphine N-demethylation is used as a marker pathway in studies of rat cytochrome P450 3A and 2C11 biotransformations. At present, microsomal activities are generally measured by a colorimetric determination of the formed formaldehyde. In the present study, a high-performance liquid chromatographic method of separating and quantifying both the N-demethylated (norethylmorphine) and the O-de-ethylated (morphine) metabolites is described. Either samples are extracted with ethyl acetate or proteins are precipitated with zinc sulphate barium hydroxide. Separation is achieved on a CN reversed-phase column, using a mobile phase of phosphate buffer (pH 4.5)-acetonitrile (90:10, v/v). At a flow rate of 1.5 ml/min, the analysis time is 30 min. The limit of detection (ultraviolet, 210 nm) for ethylmorphine and its metabolites is 0.5 micrograms/ml. PMID- 1447344 TI - Reversed-phase high-performance liquid chromatographic separation of the stereoisomers of labetalol via derivatization with chiral and non-chiral isothiocyanate reagents. AB - The antihypertensive agent labetalol is a mixture of two racemates. We report reversed-phase high-performance liquid chromatographic (HPLC) methodology for the separation of the four stereoisomers of labetalol via derivatization with the chiral reagent (4S-cis)-2,2-dimethyl-5-isothiocyanato-4-phenyl-1,3-dioxane. The derivatives were separated on octadecylsilane columns with a methanol-ammonium phosphate buffer mixture as mobile phase. Separations of the diastereomeric forms of labetalol were achieved with the non-chiral derivatizing reagents benzyl isothiocyanate and 1-naphthalenemethyl isothiocyanate. In all cases the derivatives of the R,S/S,R forms eluted before those of the R,R/S,S forms. Isothiocyanates may have general utility in stereoisomer separations of amines by HPLC. PMID- 1447345 TI - Determination of nalbuphine using high-performance liquid chromatography coupled to photodiode-array detection and gas chromatography coupled to mass spectrometry. AB - A procedure involving capillary column gas chromatography coupled to mass spectrometry and a method involving liquid chromatography coupled to a diode array detector have been developed for the analysis of nalbuphine. The extraction step is the same for both techniques and involves extraction under alkaline conditions in chloroform-2-propanol-n-heptane (50:17:33, v/v/v) with levallorphan as the internal standard. After purification by acidic extraction and back alkaline extraction, drugs are derivatized with N,O-bis (trimethylsilyl)trifluoroacetamide with 1% trimethylchlorosilane for gas chromatography-mass spectrometry and directly injected for high-performance liquid chromatography-diode-array detection. The limits of detection are 2.0 and 25.0 ng/mg, respectively. PMID- 1447346 TI - Improved high-performance liquid chromatographic procedure for the determination of lasalocid in chicken tissues and egg using polymeric and porous graphitic carbon columns. AB - A high-performance liquid chromatographic (HPLC) method for the determination of the ionophore coccidiostat lasalocid in poultry muscle and eggs was developed. The drug was extracted from tissue with acetonitrile. The extract was partitioned between saturated salt and carbon tetrachloride and the organic layer evaporated to dryness. Clean-up was by solid-phase extraction on a silica column. HPLC analysis was carried out on either a polymeric PLRP-S or a porous graphitic carbon Hypercarb column with a basic mobile phase and fluorescence detection with excitation at 310 nm and emission at 420-430 nm. Average recoveries from poultry muscle at the 0.002, 0.010 and 0.050 mg kg-1 levels were 65.7, 72.0 and 77.9%, respectively. Average recoveries from egg at the 0.010 and 0.100 mg kg-1 levels were 76.2 and 76.4%, respectively. PMID- 1447347 TI - Sensitivity and specificity of urinary N-acetyldopamine as a marker for neuroblastomas: comparison with traditional urinary catecholamine metabolites. PMID- 1447348 TI - High-performance liquid chromatographic determination of morphine, morphine-3 glucuronide, morphine-6-glucuronide and codeine in biological samples using multi wavelength forward optical detection: a reply. PMID- 1447349 TI - High-performance liquid chromatography-thermospray mass spectrometry of hydroperoxy polyunsaturated fatty acid acetyl derivatives. AB - A method for the analysis of hydroperoxy polyunsaturated fatty acids was developed. The hydroperoxy groups were acetylated by acetic anhydride, and the mixture was partially purified on a Sep-Pak C18 cartridge and analysed by high performance liquid chromatography with thermospray mass spectrometry. Generally, the base ion, [M+H - n(60)]+ or [M+H - n(60) - n(H2O)]+, is produced through elimination of acetic acid or water (n = number of hydroperoxy groups). The detection limit for these derivatives was ca. 1 pmol at concentrations of hydroperoxy polyenoic acids prior to derivatization. Using this method, many hydroxy and hydroperoxy polyunsaturated fatty acid derivatives could be detected simultaneously within 30 min on a selected-ion monitoring detection chromatogram without a gradient system. The assay was successfully applied to hydroxy and hydroperoxy polyunsaturated fatty acids from an incubation mixture of rat brain homogenate to which polyunsaturated fatty acids had been added. PMID- 1447350 TI - Determination of carnosine and other biogenic imidazoles in equine plasma by isocratic reversed-phase ion-pair high-performance liquid chromatography. AB - The isocratic reversed-phase ion-pair high-performance liquid chromatographic technique presented provides a sensitive, rapid and reproducible analytical method for the selective determination of carnosine and other biogenic imidazoles in equine plasma. Plasma was deproteinized with 5-sulphosalicylic acid and the compounds of interest were isolated by sorbent extraction on Bond Elut PRS cartridges. Recoveries were 97-105% and the lowest limits of detection were 58.3 80.1 nM. All compounds of interest were well resolved within a maximum retention time of 9.2 min. The mean equine plasma carnosine level determined by this method was 11.31 microM. Comparative determinations were made in canine and human plasma. Carnosine was not detected in human plasma. Concentrations of imidazole in canine plasma are reported here for the first time. PMID- 1447351 TI - Measurement of total plasma and cerebrospinal fluid homocysteine by fluorescence following high-performance liquid chromatography and precolumn derivatization with o-phthaldialdehyde. AB - Precolumn derivatization of amino acids with o-phthaldialdehyde followed by high performance liquid chromatographic separation and fluorescence detection is used in many clinical and experimental laboratories for the measurement of primary amino acids. This technique was adapted for the measurement of homocysteine in plasma and cerebrospinal fluid (CSF) following alkylation of the free sulphydryl group with iodoacetate. The minimum detection limits are less than 1 microM in plasma and 80 nM in CSF. Within-day and between-day coefficients of variation for plasma and for CSF are less than 10%. Values for normal plasma homocysteine range from 6.04 to 16.2 microM and for CSF from 0.28 to 0.66 microM. PMID- 1447352 TI - Monitoring of an experimental red blood cell pathology with gravitational field flow fractionation. AB - Gravitational field-flow fractionation is a simple method suitable for the separation of micrometre-size particles, for example the red blood cells (RBC). The variation in the composition of the RBC population in a rabbit during an experimental reversible anaemia induced by phenylhydrazine was studied. Blood samples taken at different stages of the anemia showed differences in the retention and shape of the elution profiles. Microscopic observations of original RBC samples and fractions collected at the outlet of the fractionation channel make a description of the RBC population possible. The three species observed were the normal RBC, the newly produced reticulocytes, and the blood cells containing Heinz bodies (intracellular haemoglobin precipitates). A decrease of the normal RBC from 96 to 1% was observed over five days. The production of reticulocytes in bone marrow is stimulated by the anaemia and increases in percentage after the second day of the anaemia (from 1 to 16%). RBC with Heinz bodies, which appear on the third day, were also studied. Granulometric studies were performed on the RBC sampled from the rabbit each day as well as on some fractions eluted by field-flow fractionation. Reinjection procedures of some cell subpopulations of known size distribution were also performed. The relaxation process of these cells was then studied to approximate their density properties. It was observed that RBC of different density but of the same average size were selectively eluted, as were cells of equivalent density but of different size. Injection of the cells at different stop-flow times enabled the study of the relaxation process on the elution profiles. The results, compared with systematic microscopic observation and size analysis, permit the description of modifications in the RBC composition as well as the purification of subpopulations at each stage of the anaemia. The correlation observed between the fractionation profiles and the progress or the regression of the anaemia opens a new field in the analytical monitoring of this type of pathology. PMID- 1447353 TI - Quantitation by gas chromatography with selected-ion monitoring mass spectrometry of "natural" diazepam, N-desmethyldiazepam and oxazepam in normal human serum. AB - During the past five years, the literature has tended to prove the occurrence of "natural benzodiazepines" in tissues and biological fluids of non-medicated humans. Several have been identified but very few papers deal with their quantitation in biological material. We present here a method for the specific and sensitive measurement of serum levels of diazepam, N-desmethyldiazepam and oxazepam by gas chromatography with selected-ion monitoring mass spectrometry in twenty human volunteers without medication. Diazepam was found over the whole population, in the range 7.3-32.0 pg/ml, identical in males and females. The other two were present in only some individuals (1.0-7.6 pg/ml for N desmethyldiazepam and 2.0-13.0 pg/ml for oxazepam). The origin (endogenous, dietary or microbial) of these substances is still to be elucidated. PMID- 1447354 TI - Electron-impact and chemical ionization detection of nicotine and cotinine by gas chromatography-mass spectrometry in rat plasma and brain. AB - Nicotine and its metabolite, cotinine, were measured in rat plasma and brain by gas chromatography-mass spectrometry. Both agents were extracted from plasma and brain, separated on a capillary column, and quantified by single-ion monitoring. The major fragment ions of nicotine and cotinine at m/z 84 and m/z 98, respectively, were monitored by electron-impact ionization detection and the protonated molecular ions at m/z 163 and m/z 177, respectively, were monitored by chemical ionization detection. Both compounds were quantified using deuterium labeled nicotine and cotinine, respectively, as internal standards. PMID- 1447355 TI - Simultaneous determination of fluoxetine and norfluoxetine enantiomers in biological samples by gas chromatography with electron-capture detection. AB - An electron-capture gas chromatographic procedure was developed for the simultaneous analysis of the enantiomers of fluoxetine and norfluoxetine. The assay involves basic extraction of these enantiomers from the biological samples, followed by their conversion to diastereoisomers using the chiral derivatizing reagent (S)-(-)-N-trifluoroacetylprolyl chloride. The method was utilized to detect and measure the quantity of these enantiomers in plasma and urine of patients and in liver and brain tissue of rats treated with (R,S)-fluoxetine. PMID- 1447357 TI - Rapid fluorimetric assay for the detection of the peptidyl alpha-amidating enzyme intermediate using high-performance liquid chromatography. AB - Peptidylglycine alpha-amidating enzyme catalyzes the conversion of glycine extended peptides to their corresponding amidated peptides via a stable alpha hydroxyglycine intermediate. Using a new rapid fluorimetric reversed-phase high performance liquid chromatographic assay, we have demonstrated that the substrate and product of the amidation reaction, as well as both stereoisomers of the alpha hydroxyglycine intermediate, can be separated and detected in quantities as low as 1 pmol. The method is highly reproducible and requires less than 11 min for separation and quantification. PMID- 1447356 TI - Rapid and sensitive anion-exchange high-performance liquid chromatographic determination of radiolabeled inositol phosphates and inositol trisphosphate isomers in cellular systems. AB - A rapid and sensitive high-performance liquid chromatographic method for the determination of multiple inositol phosphates and inositol trisphosphate isomers was developed. The separation of inositol phosphates was optimized by controlling the ionic strength with stepped gradient programs and the pH of mobile phase. Six inositol phosphates were determined within 22 min or the six compounds plus an inositol trisphosphate isomer within 24 min using a single anion-exchange column containing the quaternary ammonium functional group. This technique was successfully applied to the determination of inositol phosphatide turnover by AlF4-stimulation in a small amount (5.10(5)-1.10(6) cells) of cultured retinal capillary pericytes. Because of its efficiency, accuracy and applicability to the separation of inositol phosphates from biological samples, this method may be useful in signal transduction studies in cellular systems. PMID- 1447358 TI - Rapid determination of sulphonamides in milk using liquid chromatographic separation and fluorescamine derivatization. AB - A simple and selective method is presented for the multiple residue determination of eight sulphonamides in consumers' milk. The drugs are sulphisomidine (ID), sulphadiazine (DZ), sulphamerazine, sulphadimidine, sulphamonomethoxine, sulphamethoxazole, sulphadimethoxine and sulphaquinoxaline (SQ). The milk sample was deproteinized with the same volume of 2 M hydrochloric acid and filtered. A 1 ml volume of the filtrate was mixed with 1 ml each of 1.25 M sodium acetate solution and a buffer (pH 3.0) for derivatization with 0.6 ml of 0.02% fluorescamine solution in acetone. A high-performance liquid chromatographic analysis was carried out on a C18 column with a mobile phase of acetonitrile-2% acetic acid (3:5) at 55 degrees C using a fluorescence detector at an excitation wavelength of 405 nm and an emission wavelength of 495 nm. Average recoveries at fortification levels of 2, 5 and 10 ng/ml were 114%, 109% and 106%, respectively. Relative standard deviations were 1-4% at 10 ng/ml for ID, 5 ng/ml for DZ and SQ and 2.5 ng/ml for the other five sulphonamides. The method was applied to 25 milk samples and all appeared to be free from the drugs. PMID- 1447359 TI - Sensitive method for the determination of organophosphorus pesticides in fruits and surface waters by high-performance liquid chromatography with ultraviolet detection. AB - A sensitive method for the high-performance liquid chromatographic determination of five organophosphorus pesticides (paraoxon, methyl-parathion, ethyl-parathion, guthion and fenitrothion) in fruits and tap and river water samples is described. For the determination of pesticides in fruits a simple and rapid sample preparation procedure was developed that allowed pesticides to be determined at 50-100 micrograms/kg levels with recoveries ranging from 83 to 118% and relative standard deviations below 6%. The determination of pesticide residues in surface water samples was also successfully accomplished. Concentrations at sub-ppb levels can be measured by using a solid-phase concentration step, the recoveries being over 80%. In analyses of both fruits and surface waters, the sensitivity levels achieved were 2-10 times lower than legal limits admitted in the European Economic Community. PMID- 1447360 TI - Studies on the methanolysis of small amounts of purified phospholipids for gas chromatographic analysis of fatty acid methyl esters. AB - The methanolysis of small amounts of purified phosphoglycerides and sphingomyelin was studied and a quantitative comparison of five methods for the methanolysis of standard phosphoglycerides was made. These methods were based on methanolysis with boron trifluoride-methanol, methanolic sodium methoxide (at ambient temperature and with heating) and methanolic sulphuric acid. A further method was based on saponification with methanolic sodium hydroxide and subsequent esterification with boron trifluoride-methanol. Under the experimental conditions, only the sodium methoxide-catalysed method at ambient temperature gave complete methanolysis of phosphoglycerides. For methanolysis of sphingomyelin, boron trifluoride-methanol, methanolic sulphuric acid and methanolic hydrochloric acid were used. It was found that complete methanolysis of sphingomyelin takes 15 h at 90 degrees C. Based on these results, procedures for the methanolysis of phosphoglycerides and sphingomyelin separated by high performance liquid chromatography are presented. PMID- 1447361 TI - Coculture of embryos on Vero cells and transfer of blastocysts in humans. AB - Preliminary results are presented concerning the first clinical application of cocultures of human embryos. In the experimental group, the embryos were cultured and transferred on day 5 post-insemination. Blastocyst formation was not dependent upon the stimulation regimen. Long term or ultrashort stimulation of the ovaries after gonadotrophin releasing hormone analogue gave 55-60% blastocyst formation. Serum was not necessary to obtain blastocysts. When the embryos were cocultured, we observed an increase in the implantation rates per embryo in the pregnant patients. However, a real increase in the pregnancy rate per transfer was observed in a population of patients who had had repeated failures of embryo transfer. This observation is discussed as possibly bypassing an effect of uterine motility, but the overall beneficial effect has to be assessed in a double blind randomized study. It is probable that improvements will not be observed for all the indications for in vitro fertilization. PMID- 1447362 TI - Preimplantation diagnosis. AB - Although healthy babies have been born after preimplantation diagnosis for sex determination, this technique is still in an experimental phase. To date, removal by micromanipulation of one or two blastomeres from an eight-cell embryo seems an acceptable procedure. Since a reasonable number of biopsied embryos will implant and develop in utero, the methodology for the analysis of the blastomeres at the chromosomal, gene product or DNA level, needs to be improved before further clinical application. In the meanwhile, more information about early embryo development will become available. PMID- 1447363 TI - Transvaginal gamete intra-fallopian transfer and embryo intra-fallopian transfer. AB - This study describes the conduct and results of a recently developed technique for transvaginal catheterization of the Fallopian tube in order to transfer gametes or early embryos. Transvaginal gamete intra-Fallopian transfer (TV-GIFT) was performed in 46 patients after stimulation with human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG) and transvaginal oocyte retrieval. This resulted in 11 (23.9%) pregnancies. Eight patients delivered healthy children, including one set of twins. Two patients had abortions at 8 and 11 weeks of gestation and one had an ectopic pregnancy. In a first series of 11 women, oocytes were fertilized in vitro and a maximum of three embryos at the 2- to 8-cell stages were transferred into one tube. Three of the 11 cycles with tubal embryo-stage transfer' (TV-TEST) resulted in clinical pregnancy. PMID- 1447364 TI - Indications for in-vitro fertilization and results. AB - During the last few years, many healthy children have been born after in vitro fertilization and embryo transfer, fulfilling the wish for a child for many couples who had often nearly given up hope. Because of in vitro fertilization and other related methods developed subsequently (gamete intra-Fallopian transfer, intratubal embryo transfer), progress in the diagnosis and treatment of involuntary childlessness took place and has helped many patients. Furthermore, by dealing with these methods, new knowledge about ovarian function, fertilization and early embryonic development could be gained. This has also led to better treatment of childless couples. Despite the broad diagnostic and therapeutic possibilities of reproductive medicine, its limits must also be taken into account. These limitations have been recognized early by physicians and scientists dealing with this subject and also by society. Guidelines and laws have been drawn up which now give a clear framework. PMID- 1447365 TI - The male IVF patient--psychosomatic considerations. AB - In order to study psychosomatic considerations of the male IVF patient, three issues were investigated. First, the personality traits of sterile males (n = 180) were recorded. Male IVF patients were found to have largely the same personality traits as the general population although they tended to have more dominant and retentive traits. Second, in examining the specific stress experiences during IVF, the individual treatment steps were ranked as being similarly stressful by both partners. Males felt the waiting periods (fertilization? pregnancy?) to be clearly more unpleasant than the physical aspects of treatment (e.g. masturbation). Third, an individual comparison of sperm parameters taken during the diagnostic phase with those measured during the IVF attempt, showed that density and morphology were significantly different. Some practical recommendations to reduce the stress that men experience during IVF include his presence during the treatment steps that the female must undergo, as well as his participation in a self-help discussion group. PMID- 1447366 TI - Fallopian tube sperm perfusion: first clinical experience. AB - We have developed an insemination method using a large (4 ml) volume of the inseminate. This method incorporates ovarian stimulation, isolation of an optimal number of motile spermatozoa and, finally, Fallopian tube sperm perfusion (FSP). In a clinical study, 139 couples with various causes of infertility, had a total of 239 treatment cycles. The pregnancy rate per treatment in groups with endometriosis, ovulation disorders, tubal impairment, combined male and female factors and subnormal sperm quality were low, ranging from 2.7% to 7.7%. In patients with unexplained infertility, the pregnancy rate per treatment was 26.9% and for this group, the pregnancy rate in the first treatment cycle was 37.3%. In the cervical hostility group, two pregnancies occurred after five treatments. FSP seems to be a favourable treatment for couples with cervical hostility or unexplained infertility. About half of the women in these groups conceived after three treatment cycles. FSP is easier to perform and is less expensive than other methods of assisted procreation, such as in vitro fertilization and gamete intra Fallopian transfer. PMID- 1447367 TI - Genetic research in embryology. AB - Based on findings on the molecular mechanisms of differentiation in drosophila, developmental genes have been identified in mammals similar to those in drosophila. Moreover, sequence similarities between drosophila developmental genes and mammalian growth factors provide evidence for common ancestors of such genes and suggest a complex link between growth and differentiation. As numerous oncogenes display their action as growth factors and are expressed during embryogenesis, differentiation and oncogenesis seem to be two sides of the same coin. Therefore, the aim of molecular embryology is twofold; elucidating differentiation processes and disclosing oncogenesis by studying the physiological function of oncogenes during development. Recent progress in molecular genetic technology now allows gene function to be studied by modification or disruption of genes. Models of clinical diseases have already evolved from such work and it is anticipated that progress in molecular embryology will further stimulate work on the diagnosis and therapy of genetic diseases as well as clinical oncology. PMID- 1447368 TI - The use of gonadotrophin releasing-hormone analogues (GnRHa), in in-vitro fertilization: some clinical and experimental investigations of a direct effect on the human ovary. AB - Several lines of investigation suggest a direct modulatory role for gonadotrophin releasing hormone (GnRH) on granulosa cell functions. Also, GnRH and its analogues (GnRHa) have been implicated in the resumption of meiosis, both in vivo and in vitro. Despite the presence of specific receptors for GnRH on human granulosa and luteal cells, very little is known about the possible effects of this hormone on the ovary. The use of GnRHa for long periods of time in patients undergoing in vitro fertilization (IVF) may influence granulosa cell function and/or oocyte maturation. We describe our clinical and experimental data in which we have searched for evidence of a direct action of GnRHa on the ovary. We have found that the retrieval of higher numbers of oocytes in women treated with GnRHa is correlated with oocytes of lower quality, manifested by a decreased fertilization and implantation rate. This impairment seems to be the consequence of oocyte immaturity, as ascertained by cytogenetic analysis of unfertilized oocytes in which an increase in diploidy, as well as prematurely condensed sperm chromosomes of the G1 phase, was observed in women with an excessive response to the stimulating drugs. Follicular atresia was not increased in women treated with GnRHa. Thus, there was no evidence for a direct effect of GnRHa on the human oocyte. Rather, the observations reflect the harmful effect of pushing follicles in early stages of development using this stimulation protocol. We have also searched for possible effects of GnRHa on granulosa-luteal cells obtained at ovum collection. In vitro culture of these cells has shown that the steroidogenic pathway is affected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447370 TI - Transcervical access and intra-luminal imaging of the fallopian tube in the non anaesthetized patient; preliminary results using a new technique for fallopian access. AB - A study was performed to evaluate a new transcervical, Fallopian tube access system for use in falloposcopy procedures without the need for conventional hysteroscopy or uterine distension. Visualization was accomplished by the use of a 0.5 mm falloposcope which was delivered to the Fallopian tube by a new linear everting catheter. The linear everting catheter allows access to the Fallopian tube by means of a flexible, tubular rolling membrane which can safely negotiate the tortuous anatomy from the ostium to the ampulla. Concurrent laparoscopy was performed solely for supervision purposes and not for tubal manipulations in 13 Fallopian tube access procedures in 10 patients. The ostia were visualized in 12 cases and the Fallopian tube was accessed in all 12 without complications. As a precursor for future gamete and embryo transfer procedures, intra-tubal insemination was performed by visualizing the ostia, accessing the Fallopian tubes, and obtaining successful isthmic-ampullary, intra-luminal images. PMID- 1447369 TI - Is there an indication for embryo reduction? AB - The selective reduction of embryos in multiple pregnancies poses numerous medical, technical, ethical and psycho-social problems. In a retrospective study, we analysed nine hundred and twenty-two pregnancies obtained using medically assisted procreation between May 1982 and May 1990. Among 922 successful pregnancies, 372 were singleton, 102 were twin and 13 were triplet. Data from this analysis and from a French multicentre study of 262 embryo reduction procedures demonstrated the value of an embryo quality score for minimizing the risk of multiple pregnancy and the existence of extremely infrequent, ethically acceptable indications for embryo reduction. These indications included ultrasound-proven malformations of one fetus, multiple pregnancies in patients with extensive uterine scarring, and multiple pregnancy despite the appropriate use of preventative measures which can be expected to make this technique unnecessary in the future. PMID- 1447371 TI - Treatment of male infertility by gamete micromanipulation. AB - Over the past decade, in vitro fertilization (IVF) has become a routine and acceptable tool in the treatment of infertility. However, major limitations in solving certain infertility problems still remain. Male infertility is one area in which only a small fraction of patients have benefited from IVF. Union of male and female gametes, either in vivo or in vitro, requires sperm penetration through the cumulus oophorus and the zona pellucida. Failure of fertilization despite the increased number of spermatozoa introduced into the oocyte's vicinity by IVF, has been shown to be directly related to abnormalities in sperm cell morphology and motility. The improved technology for micromanipulation of gametes has made it possible to circumvent the oocyte barriers to sperm penetration, thereby greatly reducing the number of normal sperm cells needed to achieve fertilization. This paper reviews the three major micromanipulative strategies which have been developed over the past five years, patient selection for the different procedures and the methods of sperm preparation to improve the yield of the applied technique. PMID- 1447372 TI - Cryopreservation of rabbit zygotes. AB - Rabbit embryos at the pronuclear stage (n = 480) were frozen using a mixture of propanediol and sucrose. The survival rate was 71% according to their morphological features shortly after thawing. The viability rate after 5 days of culture was 10% according to the number of embryos that reached the blastocyst stage, while the rate of formation of blastocysts from freshly collected and cultured pronuclear embryos was higher (59%). The implantation rate was higher (24%) if the frozen/thawed zygotes were directly transferred to foster mothers after 2-4 hours of culture, whereas with zygotes cultured for 24 hours (4 to 8 cell stages) the implantation rate was poor (4%). Both rates were low compared with the implantation rate (52%) achieved with freshly collected and directly transferred pronucleate embryos. PMID- 1447373 TI - Indications for oocyte donation. AB - Donated oocytes were transferred on 92 occasions to 87 women without gonadal function and 5 with functional ovaries. Twenty-three pregnancies were established (25% pregnancy rate), 9 after transfer of fresh embryos in 30 synchronous donor and recipient cycles and 14 after transfers of frozen-thawed embryos in 62 asynchronous donor and recipient cycles. Twenty-two pregnancies were obtained in agonadal patients (25.3% pregnancy rate) and 1 in a gonadal woman (20% pregnancy rate). Pregnant women were younger than those who did not become pregnant, but the difference was not significant. The pregnancy rate was higher when intra Fallopian transfer was performed (46%) as compared with intrauterine transfer (21.5%) and when micronized progesterone was given intravaginally (pregnancy rate 30.3%) as compared to intramuscularly injected natural progesterone in oil (pregnancy rate 22%). Twenty healthy infants have been born including one set of twins; four pregnancies miscarried. PMID- 1447374 TI - Fertilization abnormalities in human in-vitro fertilization. AB - Fertilization abnormalities (premature chromosome condensation of spermatozoa (PCC), triploidy, haploidy) were analysed in order to determine their origin. PCC occurs in 9% of unfertilized oocytes and seems to be the consequence of a failure of oocyte activation, leading to the continuing presence of cytoplasmic chromosome-condensing factors, causing the sperm nucleus to undergo chromosome condensation prematurely. This anomaly appears to be related to incomplete nuclear and/or cytoplasmic maturation. Triploid zygotes (6.5% of fertilized oocytes) display an original type of division: half of them divide into 3 and 6 cells, whereas at the same time diploid zygotes divide into 2 and then 4 cells. A cytological study, using both antitubulin antibodies and Hoechst dye, allowed us to demonstrate that they divide into 3 cells by means of a tripolar spindle. Triploidy seems to be correlated with four of 16 clinical or biological parameters examined: semen origin (fresh or frozen), type of stimulation treatment, number of oocytes recovered and embryo morphology. Haploid eggs (1.6% of inseminated oocytes) result from parthenogenetic activation. A correlation was found between a high number of recovered oocytes and triploid zygotes, and the occurrence of oocyte activation. These data show that increasing follicular recruitment decreases the overall oocyte quality and maturity leading to an overall 9% with impaired fertilization. PMID- 1447375 TI - Chlorinated hydrocarbon content of fetal and maternal body tissues and fluids in full term pregnant women: a comparison of Germany versus Tanzania. AB - Chlorinated hydrocarbons are distributed worldwide and due to their lipophilic properties and chemical stability they accumulate in the foodchain. The concentrations of 19 different chlorinated hydrocarbons (hexachlorohexane (HCH), DDT and various metabolites and nine different polychlorinated phenyl (PCB) congeners were detected in various body tissues and fluids (maternal and fetal serum, adipose tissue, placenta, amniotic fluid) of full term pregnant women from Germany and Tanzania. Great variation of total toxin burden and toxin distribution within the different body compartments was found. This was in part due to local differences of exposure to some of the chlorinated hydrocarbons. Comparing samples from Germany and Tanzania, typical distribution patterns reflected the specific economic situation of the two countries with a high burden of insecticides (DDT and Dieldrin) in the agricultural country and high levels of constituents of industrial products (hexachlorobenzene (HCB) and PCBs) in Germany. Different chlorinated hydrocarbons seem to show different distribution patterns in body tissues, probably due to their chemical structure, the lipid content of the compartment and the overall toxin burden of the individual. A 10 to 100 fold accumulation of chlorinated hydrocarbons was observed in maternal adipose tissue compared with the other compartments. The concentrations of certain toxins in fetal cord serum and placenta were higher than in maternal serum. PMID- 1447376 TI - Peripheral inflammatory root resorption. A review of the literature with case reports. AB - External resorptions associated with inflammation in marginal tissues are many times misdiagnosed and confused with caries and internal resorptions. A lack of uniformity in nomenclature has added to the confusion. This paper reviews the literature and presents cases to illustrate a rational approach to diagnosis and treatment. A new name is suggested to better reflect the features of this type of root resorption: peripheral inflammatory root resorption. PMID- 1447377 TI - Granulocyte elastase in gingival crevicular fluid. A possible discriminator between gingivitis and periodontitis. AB - The granulocyte elastase activity and the immuno-reactive (antigenic) granulocyte elastase of gingival crevicular fluid (GCF) were studied in 16 periodontitis patients and in 10 gingivitis patients. The elastase activity was measured with a low molecular weight substrate specific for granulocyte elastase. The antigenic elastase was determined with specific antibodies against granulocyte elastase. Intracrevicular sampling of GCF with paper strips for 30 s seemed to provide representative values of elastase. The elastase activity correlated with probing depth and attachment loss and appeared to be a measure of the degree of tissue destruction. Antigenic elastase represents the number of granulocytes in GCF and should thus be related to the degree of inflammation. The periodontitis patients and the gingivitis patients both had a similar degree of inflammation as measured by antigenic elastase per microliter GCF and gingival index. The elastase activity per microliter GCF, however, was higher in the periodontitis group. Elevated granulocyte elastase activity in GCF seems to be independent of inflammation and could thus be an indicator of patients at risk for periodontitis. PMID- 1447378 TI - Reproducibility of an electronic probe in relative attachment level measurements. AB - 4 probing designs have been employed to investigate the reproducibility of the Florida Probe. 3 groups (each composed of 10 subjects) were selected for the study: healthy adults, gingivitis subjects, and periodontitis subjects. The 4 probing designs were as follows: (a) the probe tip was left in the sulcus between successive probings; (b) the probe tip was removed from the gingival margin between probings but the next probing followed immediately; (c) successive whole mouth probings were interrupted by a 5-min interval and a mouthrinse; (d) there was a 4-week interval between each probing. 3 measurements were taken for each design. The main purpose of this study was to identify variance components in the attachment level variation. The maximum probing error standard deviation was found to be around 0.3 mm, which is considerably smaller than that found in most previous studies. The errors associated with the periodontal condition and probing effect were also estimated. The variance components obtained here can be used for determining the sample size in controlled clinical studies. PMID- 1447379 TI - Evaluation of a new periodontal curet. An in vitro study. AB - Removal of plaque and calculus from subgingival root surfaces is a fundamental aspect of periodontal therapy. A new type of periodontal curet (Gracey Curvette Sub-0) has been designed to better adapt to the root surfaces that may be encountered in periodontal pockets of incisor teeth. The new curet (test) was compared to a Gracey curet 1/2 (conventional) in their ability to remove deposits from the subgingival root surfaces of incisor teeth in an in vitro model. A dentiform model mounted on a dental chair was used with artificial gingiva, 6 mm pocket depths and subgingival root surfaces covered with black enamel paint. 2 groups of 12 hygienists used, on a timed basis, either the test or conventional curet on 4 of the incisor teeth and then switched to the alternate instrument for the remaining four incisors. The extent of surface material removal was determined using a computerized video routine. The test curet removed significantly (p less than 0.001) more of the surface material from all subgingival incisor root surfaces than the conventional curet (60.7% versus 46.3%). Both instruments were most effective at labial surfaces. The test curet was least effective at proximal surfaces and the conventional curet least effective at lingual surfaces. The greatest statistical difference between instruments was apparent at lingual surfaces of maxillary incisors and the least at mesial surfaces of mandibular incisors. PMID- 1447380 TI - An imaging routine for assessing the efficacy of instruments used for scaling and root planing. AB - Deposits of dental plaque or calculus are typically quantified using planimetric techniques. However, error is introduced into a quantitative analysis of plaque deposits using these methods, since they require a significant amount of human intervention. The purpose of this study is to describe and validate a computerized imaging routine which has the potential to objectively identify material on dental roots and measure the area covered by these deposits. Dentiform teeth with simulated plaque were videorecorded. A computer routine was developed based on a flood-fill algorithm which analyzed images of the dentiform teeth and determined the amount of simulated plaque on their root surfaces. Results showed that the dentiform teeth and their simulated plaque patterns are duplicated by the imaging routine in a rapid and reliable fashion. The system shows a high degree of accuracy with an average error factor of only 0.58%. As well, the system enables precise reproducibility with an average error factor of only 0.71%. PMID- 1447381 TI - Comparative in vitro studies of sonic, ultrasonic and reciprocating scaling instruments. AB - Flat root surface areas of formalin-stored mandibular incisors with plaque and calculus were scaled by sonic (PHATELUS SONIC SCALER, SONIC FLEX 2000, TITAN-S SONIC SCALER) or ultrasonic instruments (HYGIENIST ULTRASONIC SCALER, CAVITRON) or by a new reciprocating scaling insert for the EVA/PROFIN system. The test areas were photographed by SEM and coded micrographs were independently graded by three examiners using the RCI (Remaining Calculus Index) and the RLTSI (Roughness Loss of Tooth Substance Index). The findings revealed that the sonic scalers as a group removed calculus more completely but also left significantly more roughness and loss of tooth substance than the other instruments tested. No difference was seen between the two ultrasonic scalers. The reciprocating insert gave results similar to those of the ultrasonic except for the scaling time which was significantly longer for the new "cleansing principle". PMID- 1447382 TI - A comparison of natural product, triclosan and chlorhexidine mouthrinses on 4-day plaque regrowth. AB - There is a continuing search for ingredients to enhance the chemical plaque inhibitory action of oral hygiene products. Sanguinarine, other natural extracts and triclosan have already been used in products. The aim of this study was to evaluate a number of triclosan and natural product rinses for effects on plaque regrowth. In particular, the influence of other rinse components were assessed, notably sodium lauryl sulphate (SLS) and zinc. The study was a randomised, blind, 9-cell cross-over design to measure the effects of each rinse on 4-day plaque regrowth from a zero baseline. 15 volunteers rinsed 2x daily with each product and plaque was recorded by area and score. The 0.2% chlorhexidine rinse (positive control) was significantly more effective, and the saline rinse (negative control) significantly less effective, than other rinses. Sanguinarine alone was little different from saline and the addition of zinc made a modest improvement in activity. The 3 triclosan/SLS rinses were more effective than the sanguinarine rinses but similar to their minus triclosan control rinse. A natural product/SLS experimental rinse was second to chlorhexidine and, in many analyses, significantly better than all other rinses, but caused some oral erosions. The results indicate that the plaque inhibitory properties of basic ingredients such as SLS may be difficult to enhance or surpass. However, the possible range of recipes, particularly using natural ingredients, provides scope for research and development in the field of oral hygiene products. PMID- 1447383 TI - Preservation of probing attachment and alveolar bone levels in 2 random population samples. AB - The present study is an attempt to elucidate the relation between ageing and loss of periodontal tissue support, by studying the occurrence of probing attachment and alveolar bone loss in two samples of randomly selected individuals. The 1st sample was recruited in Japan and comprised 319 subjects aged 20-79 years. The 2nd sample was recruited in Sweden and comprised 192 subjects aged 30-65 years. All individuals underwent a radiographic and a comprehensive clinical examination, including recordings of probing attachment level. Within the 2 samples, subsamples of individuals whose periodontal status indicated minimal experience of destructive periodontal disease were selected. In these particular subsamples, it was revealed that a substantial proportion of tooth surfaces, also in older subjects, remained with no attachment or alveolar bone loss. To a lesser extent, this could be also observed when the entire samples were analyzed, despite the presence of abundant plaque and gingival inflammation. The results indicated that intact supporting periodontal tissues can be retained in subjects of increased age and corroborate the suggestion that loss of clinical attachment and alveolar bone is not an obligatory consequence of ageing. PMID- 1447384 TI - The effect of partial denture connectors on gingival health. AB - The effect on the gingiva of a variety of relationships of a removable partial denture connector to the gingival margin was investigated in 10 subjects. Acrylic resin baseplates were designed incorporating a variety of relationships of the connector to the gingival margin. The appliances were worn for a 12 hour period daily, for 21 days. At baseline and at days 7, 21 and 49, plaque index, gingival index and probing pocket depth measurements were recorded, and subgingival plaque samples were examined using darkfield microscopy. No increase in plaque accumulation was detected in any area at any time interval. There was a significant increase in gingival index at day 21 in areas where the appliance covered the gingival margin. Small increases in probing pocket depth were recorded at day 21, there being no difference between any of the test areas. Baseline values were re-established by day 49. No significant differences were detected in the percentage of motile organisms or spirochaetes counted in the subgingival plaque samples collected from any area. It was concluded that deterioration in gingival health occurred rapidly following the insertion of a removable appliance, and that coverage of the gingival margin, irrespective of the degree of gingival relief, had a detrimental effect. PMID- 1447385 TI - Clinical effects of simultaneous ultrasonic scaling and subgingival irrigation with chlorhexidine. Mediating influence of periodontal probing depth. AB - The clinical and microbial effects of a single episode of simultaneous ultrasonic scaling and subgingival irrigation with chlorhexidine (CHX) were studied as a function of clinical probing depth in patients with adult periodontitis. 60 patients were randomly assigned to receive subgingival irrigation under cavitation with either sterile water or 0.12% CHX delivered through the tip of an ultrasonically activated scaler as part of initial periodontal therapy in a double-blind study design. 3 periodontal sites were randomly selected for examination from each patient on the basis of clinical probing depth, with 1 site being selected within each of the following ranges: 1-3 mm, 4-6 mm, and 7-9 mm. Pretreatment and post-treatment (days 14 and 28) clinical assessments included a plaque index (PI), gingival index (GI), and clinical probing depth (CPD). Subgingival specimens also were collected from 1-3 mm and 4-6 mm sites on a random subset of patients (15 per group). Plaque counts of spirochetes and motile organisms were made by darkfield microscopy. Significant reductions in PI, GI, and CPD were observed among all sites within both treatment groups at 14 and 28 days post-treatment. CHX irrigation resulted in a significantly greater reduction in CPD than did water among sites initially probing 4-6 mm at both 14 and 28 days post-treatment (25% versus 13% and 31% versus 18%, respectively). Spirochete counts were modestly but nonsignificantly reduced at 14 days post-treatment among sites 4-6 mm within both treatment groups. These results suggest that subgingival irrigation with CHX during ultrasonic scaling provides differential clinical benefits that are site-dependent. PMID- 1447386 TI - A sensitive method for the detection of immune complexes in human gingival crevicular fluid. AB - An assay for immune complexes [ICs] in gingival crevicular fluid [GCF] could be potentially useful to ascertain the risk of periodontal disease activity at specific oral sites. This paper describes and ELISA-based method sufficiently sensitive to measure ICs in GCF samples at levels below 1 microgram/ml. Static GCF samples taken from 5 adults showed IC levels ranging from 5 to 166 micrograms/ml. Additional tests of 10 GCF samples from 1 adult were conducted with complement components and indicated that either C1q or rabbit anti-human C3d was suitable as a capture agent in the assay procedure. Further application of this assay may help to assess the usefulness of IC levels in GCF samples as possible diagnostic indicators of periodontal disease activity. PMID- 1447387 TI - Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease. AB - This paper describes the development of a stable, controlled-release formulation of metronidazole for use in the treatment of periodontal disease. It is formulated as a suspension, which undergoes transformation to a release controlling, semi-solid on contact with gingival fluid. The system is based on the ability of mixtures of monoglycerides and triglycerides to form liquid crystals, i.e., reversed hexagonals, in contact with water. The reversed hexagonal form was found to have the most favourable sustained release properties, compared with those from the cubic form. The source of metronidazole is the prodrug, metronidazole benzoate, which further helps to slow down the release rate. Product characteristics are assessed by differential scanning calorimetry and viscometry. The release data derive from the results of in vitro dissolution tests. X-ray diffraction, phase diagrams, and polarized light microscopy were used to elucidate the structure of the liquid crystalline phases. PMID- 1447388 TI - Systemic absorption of metronidazole after application of a metronidazole 25% dental gel. AB - Systemic absorption of metronidazole was studied after one application of a metronidazole 25% dental gel into inflamed periodontal pockets. 14 patients with periodontal disease participated. Metronidazole gel was applied into the pockets of all teeth with probing depth > or = 5 mm, minimum 10 teeth/patient. Excess gel was carefully collected in order to calculate the amount of metronidazole applied into the pockets. Blood samples for analysis of metronidazole in plasma were taken before and up to 72 h after application. To determine the bioavailability of metronidazole administered as gel, the patients were later given an i.v. dose of 100 mg metronidazole. Metronidazole was quantified by HPLC. The mean actual dose of metronidazole in gel was 55 mg (SD: 24 mg, range: 29-103 mg). Allowing for the fact that excess gel corresponding to about 60% of the applied amount of metronidazole under normal clinical conditions may be swallowed, the systemic load after one application of metronidazole 25% dental gel will still be less than after one metronidazole 250 mg tablet. Peak plasma concentrations varied between 223 and 1303 ng/ml (mean: 581 ng/mk, SD: 320 ng/ml) and were reached within 2 to 8 h (mean: 4.4 h). The mean bioavailability of metronidazole dental gel was 71%. PMID- 1447389 TI - Concentration of metronidazole in periodontal pockets after application of a metronidazole 25% dental gel. AB - The metronidazole concentration was monitored in gingival crevicular fluid (GCF) of inflamed periodontal pockets after 1 application of a 25% gel. 12 patients with periodontal disease were included in the study. Metronidazole gel was applied with a syringe into the pockets of 10 teeth with probing depths > or = 5 mm. Samples of GCF were taken with Periopaper before application and 4, 8, 12, 24 and 36 h after application. At each time, samples from 2 teeth were pooled in order to obtain a sufficient amount of fluid for analysis. By means of a calibrated Periotron, the collected volume of GCF was measured. High-performance liquid chromatography was used to determine the amount of metronidazole. MIC50 for anaerobic periopathogens susceptible to metronidazole is below 1 microgram/ml. In this study, the concentration obtained was higher than 1 microgram/ml in all samples after 4 and 8 h, in 92% after 12 h, in 50% after 24 h and in 8% after 36 h. Thus, metronidazole concentrations in the pockets were generally above MIC50 for susceptible periopathogens 24 h after 1 application of a 25% metronidazole gel. PMID- 1447390 TI - The effect of topical metronidazole therapy on experimentally-induced periodontitis in the beagle dog. AB - The present study was performed to assess the effect of topical metronidazole therapy on ligature-induced periodontitis in beagle dogs. 6 beagle dogs with experimentally-induced periodontitis on the mandibular 2nd, 3rd and 4th premolars were treated with metronidazole 10% dental paste 2 x daily for 4 weeks in an open placebo-controlled study using a split-mouth design. Recordings of probing pocket depth, bleeding on probing and gingival index were performed before commencement of treatment and repeated weekly during the 4-weeks treatment period. Concurrently, samples for microbiological analysis were collected from 2 of the dogs. The results demonstrated that probing pocket depth, bleeding on probing and gingival index had improved significantly in the metronidazole-treated side compared with the placebo-treated side. Black pigmented Bacteroides spp. and Spirochetes, present in all samples before treatment, were eliminated from the metronidazole-treated side after the 1st week of treatment and throughout the treatment period, whereas they were present in all samples from the placebo treated side. The result of the present study demonstrates that topical application of metronidazole in a dental paste, improves the clinical features of the experimentally-induced periodontitis and eliminates some of the micro organisms associated with the disease. PMID- 1447391 TI - 3 regimens of topical metronidazole compared with subgingival scaling on periodontal pathology in adults. AB - This report presents the findings from an open randomized multicentre clinical trial designed to compare the clinical efficacy of scaling with application of 3 different preparations/dose frequencies of topical metronidazole in the treatment of adult periodontitis. The 4 treatments were: (A) metronidazole 25% dental gel administered 1 x a week for 2 weeks; (B) metronidazole 15% dental gel applied 1 x a week for 2 weeks; (C) metronidazole 15% dental gel applied 2 x a week for 2 weeks; (D) subgingival scaling, performed 1 x only. A split mouth design was used. Patients were included in the study if they had at least 1 tooth in each quadrant with a pocket depth > or = 5 mm in at least 1 of 4 sites. A total of 61 patients from 4 centres were entered into the study. The efficacy parameters were probing pocket depth and bleeding on probing. Follow-up visits for recording of clinical efficacy were made at 2, 4, 6 and 12 weeks after the end of metronidazole treatment. All 3 antibiotic treatments (A, B, C) reduced the symptoms of periodontal pathology and yielded results comparable to those seen after subgingival scaling (D). When using a topical drug therapy, it seems important to use a preparation that requires as few applications as possible. The best candidate for drug therapy would therefore be treatment (A) metronidazole 25% applied 1 x a week for 2 weeks. PMID- 1447392 TI - Clinical responses to subgingival application of a metronidazole 25% gel compared to the effect of subgingival scaling in adult periodontitis. AB - A newly developed metronidazole 25% dental gel was compared with subgingival scaling in the treatment of adult periodontitis. 206 patients in 9 centres participated in the study. Probing pocket depth (PPD) and bleeding on probing (BOP) were recorded before treatment and 2, 6, 12, 18, and 24 weeks after the treatment. All patients had at least 1 tooth in each quadrant with a PPD of 5 mm or more. The treatments consisted of 2 applications of dental gel (days 0 and 7) in 2 randomly selected quadrants (split mouth design) and 2 sessions of subgingival scaling (1 quadrant on day 0, and 1 quadrant on day 7). Instruction in oral hygiene was given 2 weeks after completed treatment. The average PPD and the average frequency of BOP were calculated over all sites with initial PPD of 5 mm or more. PPD and BOP were thus, at each examination, calculated from the same sites. The mean PPD was 5.9 mm before gel application and 5.8 mm before scaling (p = 0.31). BOP was 88% in both treatment groups. 24 weeks after the treatment, PPD and BOP were significantly reduced in both groups and for both parameters (p < 0.01). PPD was reduced by 1.3 mm after gel application and 1.5 mm after scaling; BOP was reduced by 32% and 39%, respectively. The difference between the treatments was statistically significantly, but considered as clinically unimportant. PMID- 1447393 TI - Sharing regulatory review costs. PMID- 1447394 TI - Retinoids in cancer treatment. AB - Since initial studies identifying the important role of vitamin A and its derivatives (retinoids) in maintaining the integrity of epithelial tissues, these compounds have served as paradigms for experimental studies exploring the pharmacologic modification of carcinogenesis. Retinoids have clearly been shown to inhibit chemically induced mammary and urothelial carcinogenesis in experimental animals. Prohibitive toxicity of the parent compound, vitamin A, led to a systematic search for synthetic derivatives with an improved therapeutic index. More than 1500 such compounds have been synthesized, many retaining chemopreventive potential, but with less toxicity. Although several anecdotal reports confirming therapeutic benefits of cis-retinoic acid in patients with acute promyelocytic leukemia and myelodysplastic syndromes appeared in the late 1970s and early 1980s, the remarkable studies of Huang and his colleagues in China in 1988 reporting complete remissions in patients with this uncommon variety of acute myelogenous leukemia with the transisomer of retinoic acid (all trans-retinoic acid) led to a resurgence of interest in the retinoids as differentiating agents for the prevention and therapy of cancer. Furthermore, molecular studies showing DNA rearrangements of the alpha nuclear receptor for retinoic acid located on chromosome 17 in patients with acute promyelocytic leukemia, a disease invariably associated with a translocation between chromosomes 15 and 17, provided a direct connection between an altered nuclear receptor and the development of a human malignancy. The retinoids also may have important beneficial effects in prevention of recurrent malignancies once the primary tumor has been treated, such as in squamous cell carcinoma of the head and neck. Because retinoids appear to be less effective in inducing differentiation in nonpromyelocytic leukemia cells, investigators have conducted a number of studies to exploit potential synergism between retinoids and other differentiating agents or biologic effectors. Differentiation therapy and chemoprevention are attractive alternative approaches to intensive cytotoxic chemotherapy. It is now clear that retinoids represent one class of compounds with which it may be possible to reverse the progression of malignant disease and prevent carcinogenesis. PMID- 1447395 TI - A comparison of regulatory approval times for new chemical entities in Australia, Canada, Sweden, the United Kingdom, and the United States. AB - Regulatory approval times of new chemical entities (NCEs) in Australia, Canada, Sweden, the United Kingdom (UK), and the United States (US) were compared. The approval times of a set of common 25 NCEs and a larger set of unmatched NCEs were very similar in Australia, Canada, Sweden and the US, with median approval times from 23 to 29 months. The median approval time in the UK was approximately 11 months. Analysis of the data showed that the approval times in Australia, Sweden, and the UK were not significantly affected by the therapeutic classification of the drug, the amount of additional data requested and received, or the submission date. In Canada, the date the drug submission was received and the frequency of additional data requests significantly affected the approval times. In the US, the date the drug submission was received and the frequency of additional data received significantly affected the approval times. The therapeutic classification of the drug did not significantly affect the approval time in Canada or the US. PMID- 1447396 TI - Advances in the diagnosis of adverse drug reactions. AB - The clinician plays a key role in the detection and diagnosis of adverse drug reactions (ADRs). The diagnosis of ADRs, however, is a complex task. In the past, there were no systematically applied diagnostic criteria for ADRs, no formal methods of case analysis, no standardized epidemiologic approaches, and a limited knowledge of mechanisms. This resulted in the overdiagnosis of ADRs, which has negative consequences such as limiting treatment options. Recently, there have been various improvements in the diagnosis of ADRs, such as the development of standardized decision aids and of in vitro diagnostic tests. This article briefly reviews some of this knowledge, discusses the role of in vivo and in vitro rechallenge, and summarizes a probabilistic approach for collecting relevant information and diagnosing ADRs. The intention is to increase awareness of the different approaches for diagnosing ADRs as well as to stimulate researchers to continue to collect pharmacoepidemiologic information, study the pharmacologic, immunologic, and genetic factors involved in the pathogenesis of drug reactions, and develop and test new diagnostic instruments under various clinical conditions. PMID- 1447397 TI - N-acetylation polymorphism and diabetes mellitus among Saudi Arabians. AB - The acetylator phenotypes of 200 Saudi diabetics and an equal number of control subjects of the same origin were determined by measuring the peak height ratio of two urinary caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX), using a simplified high-performance liquid chromatographic method. Urine samples were collected from the diabetics and the control subjects who regularly drink coffee, tea, or caffeinated beverages as part of their normal daily diet. The patients were classified as either type 1 (insulin-dependent) (28 patients) or type 2 (insulin-independent) diabetics (172 patients) according to standard criteria. The reproducibility of acetylator phenotype was established by examining the peak height ratio of AFMU/1MX in 18 diabetics and 6 control subjects on different days. Significant differences in the proportion of rapid acetylators were observed between type 1 (53.6%) and type 2 (33.7%) diabetics (P < or = .0436), and between the control group (26%) and the overall diabetics (36.5%) (P < or = .024) or those with type 1 disease (P < or = .0028). Also, there was a significant (P < or = .0436) association between rapid acetylator status and type 1 diabetes mellitus. PMID- 1447398 TI - Arithmetic versus harmonic mean values for cyclosporin-A pharmacokinetic parameters. AB - The harmonic and arithmetic mean values for volume of distribution at steady state, half-life, and clearance of intravenous cyclosporin-A were calculated using an index set of 22 renal transplant candidates to determine if harmonic mean values provide a less biased estimate of central tendency than arithmetic mean values. Cyclosporin-A was measured using a nonspecific radioimmune assay method. The arithmetic mean value for volume of distribution was 16% larger than calculations by the harmonic mean method. Similarly, the arithmetic mean half life and clearance values were larger than harmonic mean values by 10% and 15%, respectively. However, 95% confidence intervals for these pharmacokinetic parameters overlapped. When these mean pharmacokinetic parameter values were used to predict actual values in a test group of 22 renal transplant candidates receiving cyclosporin-A, similar levels of precision were demonstrated by either method. Both methods produced positively biased predictions for volume of distribution and clearance. However, these differences were not significant. These findings suggest there is little practical value for the use of harmonic mean calculations to describe the central tendency of pharmacokinetic parameters of cyclosporin-A under the conditions studied. The value of harmonic mean values for pharmacokinetic parameters in other patient populations or with other assay methods for cyclosporin remain to be studied. PMID- 1447399 TI - Mirror images: the analysis of pharmaceutical enantiomers. AB - Pharmaceutical enantiomers often exhibit different pharmacodynamic and pharmacokinetic properties. Stereospecific chromatographic assays are available to separate these stereoisomers. Therapeutic agents often contain chemical functional groups (e.g. amino, hydroxyl, carbonyl, and carboxylic acid). These can be reacted with enantiomerically pure reagents to give diastereoisomers suitable for analysis on achiral gas chromatographic (GC) and high performance liquid chromatographic (HPLC) columns. Alternatively, derivatized or underivatized drugs may be resolved on chiral chromatographic phases. A wide variety of GC (e.g. amino acid, cyclodextrin, and metal-complex) and HPLC (mobile phase additive, crown ether, pi-pi interaction and related phases, protein, cyclodextrin, polysaccharide, methacrylate and amide polymer, and ligand exchange) columns are commercially available. This article reviews the chromatographic separation of enantiomers. PMID- 1447400 TI - The importance of stereochemistry in drug action and disposition. AB - Many biologically active synthetic drugs contain chiral centers, although they are used as racemic mixtures. Enantiomers are hard to distinguish in the chemical laboratory but are readily discriminated in the body and differ in their biological activities and disposition. The pharmacokinetic profiles of enantiomers can be variable, especially for drugs with a first-pass effect and enantioselective pharmacokinetic monitoring should be carried out. Ultimately, whether to exploit a racemate or a single enantiomer in therapy is a multi faceted decision to which drug disposition data have important contributions to make. PMID- 1447401 TI - Stereochemistry and bioequivalence. AB - Despite the fact that many important drugs are chiral, for a variety of reasons they are marketed as racemates (i.e., an equal proportion of two enantiomers). Although enantiomers of racemic drugs often differ from one another in their pharmacodynamic and pharmacokinetic properties, bioequivalence assessments are made using nonstereospecific assays. Such an approach may provide a poor assessment of therapeutic equality. This can be true particularly for drugs with complicated pharmacokinetics and those that exhibit extensive stereoselectivity in their disposition kinetics. Accordingly, examples of bioequivalence studies based on stereospecific assays have started to appear in the literature. Fortunately, facile stereospecific assays have become available in the last several years for many drugs. Consequently, regulatory agencies have started to take the issue of stereochemistry into consideration in the assessment of bioequivalence, particularly from the standpoint of generic substitution. PMID- 1447402 TI - Bioequivalence of racemic drugs. AB - Although pharmacokinetic and pharmacodynamic differences between the enantiomers of a chiral drug have been known or suspected for many years, racemate drugs have frequently been developed and approved without clinical pharmacologic consideration of their chiral components. In the late 1970s, the technology to isolate, manufacture, and detect pure enantiomers of racemate drugs became generally available. This availability has created new demands on both pharmaceutical firms and regulatory agencies. To prepare for this new technology, the Center for Drug Evaluation and Research at the Food and Drug Administration is formulating a policy statement to guide evaluation of new chiral drugs. At this time, it appears that whatever new policies are developed will not necessarily be applied retroactively to previously approved racemate drugs. Additional policies to guide the development and approval of generic and OTC chiral drugs may be required. In the Office of Generic Drugs in the Center, abbreviated new drug or antibiotic applications are approved on the basis of adequate chemistry, manufacturing, and control procedures and comparative pharmacokinetics (bioequivalence). The generic drug must be a racemate or single enantiomer if the corresponding innovator drug is a racemate or single enantiomer respectively. Whether a generic firm will be required to provide bioequivalence information on enantiomers of a racemate is determined on a case-by-case basis. Although it might be claimed that a generic drug product should be required only to undergo the same general kind of pharmaceutical evaluation as did the innovator, there may be instances when the approval of a generic drug or antibiotic will require measurement of specific enantiomers of a chiral drug. PMID- 1447403 TI - Pure enantiomers of 2-arylpropionic acids: tools in pain research and improved drugs in rheumatology. AB - The mode of action of aspirinlike drugs in pain is widely referred to as inhibition of prostaglandin synthesis. Salicylic acid, however, at low doses, is an analgesic but not a potent anti-inflammatory agent. This "enigma" may be resolved by recent findings employing 2-arylpropionic acids. Pure enantiomers of these chiral drugs show a different pharmacodynamic and pharmacokinetic profile. Using pure enantiomers of flurbiprofen, ibuprofen, and ketoprofen, we could show that (1) R-enantiomers of these drugs are inverted to S-enantiomers to a different degree in different species, including humans, (2) the pharmacokinetic parameters of both pure enantiomers differ in a drug- and a species-specific manner, and (3) both enantiomers exert differential analgesic effects. It appears particularly interesting that R-flurbiprofen, for instance, which is not or only to a small extent inverted in humans and rats, is practically devoid of prostaglandin synthesis inhibition in vitro. Consequently, in line with current thinking, R-flurbiprofen is not toxic to the gastrointestinal tract and shows no anti-inflammatory effects. In contrast to current concepts, however, this enantiomer does exert analgesic activity in different models of pain and nociception. It is concluded that R-flurbiprofen and, possibly, other R enantiomers of 2-arylpropionic acids may exert novel analgesic effects independently of peripheral prostaglandin synthesis inhibition in inflamed tissue. PMID- 1447404 TI - Regulatory requirements for generic chiral drugs. PMID- 1447405 TI - Unique topographic separation of two spectral classes of cones in the mouse retina. AB - We have found two immunologically distinguishable cone types in the retina of the mouse, each localized to two opposite halves of the eye. One cone type was labelled by the monoclonal antibody COS-1 specific to the middle-to-long wave sensitive visual pigment of the mammals, while the other type was stained by the shortwave-specific monoclonal antibody (OS-2). These results were confirmed with other antibodies directed against specific sequences of the visual pigments. As a result of the uneven distribution of the two cone types the mouse retina is divided into two fields separated by an oblique meridional line. The middlewave sensitive cones were present exclusively in the dorsal half of the mouse retina (M-field). The overwhelming majority of the shortwave sensitive cones occupied the ventral half (S-field), and only a small number was scattered among the middlewave sensitive cones in the dorsal retina. The ratio of the two cone types in the M-field corresponds to what has been found in the retina of other mammals, including rodents such as the gerbil and the rat. The S-field represents an entirely unique area with the unusually great number of shortwave sensitive cones and with the complete lack of the middlewave sensitive ones. The present study provides the structural basis for dichromacy in a rodent species considered for a long time to be monochromat. In addition, it shows that the ventral retina, containing exclusively S-cones in a relatively high density, is a unique retinal field not present in other mammalian species studied so far. PMID- 1447406 TI - Central projections and motor nuclei of the facial, glossopharyngeal, and vagus nerves in the mormyrid fish Gnathonemus petersii. AB - Most of the information about the anatomy of the fish's cranial nerves was collected in the first two decades of this century. Experimental analysis of the VIIth, IXth, and Xth cranial nerves by modern tract tracing techniques started about 20 years ago. Several species have been investigated to date, including one species of Agnatha (Myxinoidea), two species of elasmobranchs, and species of some orders of Teleostei like Cyprinidae, Siluriformes, Perciformes, and Gadidae. The sensory and motor nuclei of the VIIth, IXth, and Xth cranial nerves of Gnathonemus petersii were studied by anterograde and retrograde axoplasmatic transport of horseradish peroxidase and cobaltous lysine complex. The sensory nuclei form a continuous column of cells in the brain stem extending caudal to the obex. The rostral one-fourth of this column is occupied by the overlapping terminals of the VIIth and IXth nerves. The vagus nerve has 5 roots. The first 4 of these innervate the gills and the fifth supplies viscera. Afferents from the gills terminate ipsilaterally rostral to the obex in topographic order and their terminal fields overlap. Viscerosensory fibers terminate ipsilaterally in the obex region and bilaterally in the commissural nucleus of Cajal. The facial motor nucleus is located rostral to the sensory nucleus. Facial motoneurons have pear shaped and multipolar perikarya. Their axons form a rostrally directed knee before leaving the brain. The motoneurons of the IXth and Xth nerves have a common cell column. The vagal motoneurons form a periventricular, a medial, and an intermediate cell group rostral to the obex. In the obex region and also caudal to it, a lateral and a caudal group can be distinguished. Vagal motoneurons show a topographic arrangement that is similar to that of the sensory vagal projections. The majority of motoneurons have pear-shaped perikary and ventrolaterally oriented dendrites. In the caudal nucleus the dendrites extend dorsally and overlap the terminals of sensory fibers. The axons form a dorsolaterally directed arch before joining the sensory roots. Since G. petersii uses its electrosensory system primarily for detection of food, its gustatory system is less developed than in other fishes, which possess a large number of taste buds. PMID- 1447407 TI - Cytoarchitectonic organization and morphology of cells of the field L complex in male zebra finches (Taenopygia guttata). AB - The organization of the field L complex, a thalamorecipient auditory region in the telencephalon of birds, was examined in Nissl and Golgi preparations of male zebra finches (Taenopygia guttata). The field L complex comprises five cytoarchitectonic subdivisions: L1, L2a, L2b, L3, and L, although the border between L and L2b is not distinct. L2a is a plate extending dorsocaudally from the dorsal medullary lamina in the caudal neostriatum. L1 lies on the anterodorsal border and L3 lies on the posteroventral border of L2a. L, the area designated "field L" by Rose (J. Psychol. Neurol., 1914, 2:278-352), forms the medial and posterior borders of the field L complex. L2b is a thick band that forms the dorsal and dorsolateral boundary of the field L complex and is continuous with L medially. Nucleus interface (NIf) is a nucleus that lies between L2a and L1 near the lateral edge of the complex. The four types of Golgi stained neurons that occur in the zebra finch field L complex correspond to those described for the European starling (Sturnus vulgaris). Additionally, type 3 neurons are subdivided into "unoriented" neurons with spherical dendritic fields and "oriented" neurons with bipolar dendritic fields. NIf contains a distinct class of neurons that have large somata with both thick and thin spiny dendrites. The distribution of Golgi cell types between the subdivisions of the field L complex corresponds to the morphology of cells seen in Nissl material. Type 3 oriented cells are found almost exclusively within L2a. L3 has significantly greater numbers of the largest cells (type 1) and significantly smaller numbers of the smallest cells (type 4) than does L1. There are no significant differences in the distribution of Golgi stained cells between L2b and L. PMID- 1447408 TI - Design and control of the head retractor muscle in a turtle, Pseudemys (Trachemys) scripta: I. Architecture and histochemistry of single muscle fibers. AB - We are using the head retractor muscle (RCCQ) of a turtle, Pseudemys scripta, to analyze the neuromuscular mechanisms by which organisms vary the force and timing of muscle contraction. Previously we demonstrated that RCCQ comprises three histochemically defined fiber types: fast glycolytic (Fg), fast oxidative glycolytic (FOG), and slow oxidative (SO). In the present paper we report the 1) architectural features of single muscle fibers in RCCQ, including their lengths, diameters, and taper characteristics, 2) histochemical profiles of single muscle fibers, and 3) quantitative relations between our architectural and histochemical variables. Single fibers in RCCQ exhibit an order of magnitude variation in length (4-60 mm). Approximately 40% span the full muscle. The remaining fibers generally attach to bone or tendon at one end, and the other end tapers intramuscularly; rarely a fiber may taper at both ends. The maximum (untapering) diameters of single fibers are bimodally distributed, forming two diameter classes. Fibers also vary in the percentage of their total length that tapers and in the shape of the tapering region. Large diameter muscle fibers generally are longer and have shorter, more blunted tapers than small diameter fibers. The large diameter fibers are almost all Fg types; these fibers have a median diameter of 59.3 microns, and they account for approximately 60% of total fibers in RCCQ. FOG and SO fibers generally have small diameters (median: 32.5 microns and 35.8 microns), and they typically account for 30% and 10% of total fibers. We use these relations to draw inferences about the attachments and architecture of glycolytic (Fg) and oxidative (FOG, SO) fiber types. Taken together, our data suggest that single muscle fibers in RCCQ may be architecturally as well as histochemically specialized to perform different roles in head retraction. In the accompanying paper we report the efferent innervation of these fibers and consider some of the neural control problems posed by these diverse fiber types. PMID- 1447409 TI - Parent-child agreement on children's behaviours reported by the Child Behaviour Checklist (CBCL). AB - The authors examined agreement between parent and child ratings on the Child Behaviour Checklist in a sample of 1299 referred adolescents over a period of three years. Correlations ranged between 0.72 and 0.08 (mean = 0.28), while agreement using kappa was similar but slightly lower (mean = 0.24; range 0.71 0.07). Agreement on externalizing was higher than on internalizing items, and concordance increased with age for boys, while there were no differences in parent-child agreement between boys and girls. Agreement was higher for dimensions of behaviour, e.g. depression (r = 0.40). PMID- 1447410 TI - Erotomania in an adolescent: clinical and theoretical considerations. AB - Erotomania is a relatively rare delusional syndrome, typically seen in heterosexual women of middle-age or beyond. This is the first reported occurrence in an adolescent, and one of very few involving homosexual orientation. A detailed case report is discussed in the context of adolescent developmental phenomena, including "crushes", identity formation, and the resolution of sexual orientation. The presentation of erotomania as alleged sexual abuse, and a possible etiologic role for childhood sexual trauma, are considered. PMID- 1447411 TI - Preference for outdoor play during early adolescence. AB - The present study examined the extent to which boys' and girls' preference for outdoor, vigorous activity changed as they became socialized to middle school. A sample of 133 boys and girls were studied for one year: those just beginning middle school (sixth graders) and those with one year experience (seventh grade). Measures of children's preference for the playground, the duration of their stay outdoors, and behaviors while outdoors were obtained through direct observational methods. Additionally, teachers' rated children's level of achievement, physical attractiveness, and facility in games. Children also rated each other in terms of dominance status. Results indicated that boys', compared to girls', preference to play outdoors existed only in sixth grade. Factor analyses indicated that three factors described these children: Teachers' Choice, Active Female Oriented, and Outdoor Male Oriented. All three factors varied as children progressed through middle school. Results are discussed in terms of life course developmental theory. PMID- 1447412 TI - Adolescents' perceptions of significant individuals in their lives. AB - 180 adolescents, aged 11-12 years, and 180, aged 15-16 years, from one Scottish secondary school participated in this study. The purposes of the investigation were: to determine the most significant family member and unrelated person in young peoples' lives; and to identify which characteristics rendered these persons important. 'Mother' and '(same sex) friend' emerged as the outstanding choices. Family members (except siblings) were associated with positive characteristics, whilst amongst unrelated adults, youth group leaders were viewed positively. By contrast, school teachers were primarily seen as occupying a challenging role. Where age and sex differences were found, it was invariably those in early adolescence and females who were more likely to attribute positive characteristics. These results are discussed in relation to the concept of 'mentoring' and the role of mentors in adolescents' lives. PMID- 1447413 TI - Ethnic identity and self-esteem: an exploratory longitudinal study. AB - Recent models of ethnic identity formation in minority youth suggest a progression over time from an unexamined or diffuse stage to an achieved ethnic identity. To examine changes with age in ethnic identity and self-esteem, eighteen adolescents from three ethnic groups (Asian American, Black, and Hispanic) were assessed at age 16 and three years later. Results of this exploratory study showed a significant change to higher stages of ethnic identity over the three-year period. Self-esteem and ethnic identity were significantly related to each other at each time period and across the three-year time span. PMID- 1447414 TI - Moratorium-achievement (MAMA) cycles in lifespan identity development: value orientations and reasoning system correlates. AB - Three important questions emerging in identity research are: Why do only some persons with Foreclosed identities move on to Identity Achievement? Why do some Identity Achievement persons move "back" to Foreclosure? How can life-span identity re-formulation be accounted for? This study proposes that individual's positions on two variables, "instrumental vs. experiential orientation" and formistic vs. dialectrical thinking, may be important in answering these questions. Among 60 university students, 23 males and 37 females, those in an identity status characterized by formation and maintenance of structure (Foreclosure) were instrumentally-oriented while those characterized by openness to change and revision (Moratorium) were experientially-oriented. Similarly, more Moratoriums than other statuses were high in dialectic thinking. These results are discussed in terms of their theoretical implications for life-span identity development. PMID- 1447415 TI - Interpersonal needs in middle adolescents: companionship, leadership and intimacy. AB - Recent research suggests that, along with identity, intimacy is an important developmental construct during adolescence. Are there gender differences in current society regarding intimacy development? Two hundred and seven middle adolescents (70 males and 137 females) were measured using Schutz's (1958) Fundamental Interpersonal Relationship Inventory (FIRO). The FIRO is a self report survey which assesses the subject's perceived expressions and perceived desires in three categories of interpersonal relationships: Inclusion (companionship), control (leadership), and affection (intimacy). Results indicated that there were differences in expression of inclusion, control, and affection, and desire for inclusion and affection. A second analysis addressed the perceived ranking in importance of the three interpersonal categories measured. Males ranked control expressed highest and affection desired lowest; females ranked affection desired as highest and control expressed lowest. Both groups ranked inclusion desired and expressed as moderate. The current research suggests that gender differences in the development of intimacy may occur as early as middle adolescence. PMID- 1447416 TI - Perceived parental rearing, personality and mental status in Japanese adolescents. AB - As a part of a prospective study on the psychological adjustment of Japanese teenagers enrolled in a foreign exchange student program, the Parental Bonding Instrument (PBI), the Maudsley Personality Inventory and the General Health Questionnaire (GHQ) were administered to 130 females and 47 males aged 17 through 19 before departure. Parental practices were found to influence personality features, which in turn contribute to the mental health status, but no direct significant relationship was found between the PBI and GHQ measures. The last finding is in contradistinction to the previous reports which report low care and high overprotection in unipolar depressives and anxiety disorder patients but in accordance with a recent finding which failed to replicate them in general population. It is possible that the earlier findings in clinical populations were a case of Berkson bias. PMID- 1447417 TI - Relationship between parental socio-economic status, sex and initial pubertal problems among school-going adolescents in Nigeria. PMID- 1447418 TI - [Synthetic bioantioxidants--inhibitors of acetylcholinesterase activity]. AB - The inhibitory effects of synthetic antioxidants (3-oxypyridine, pyrimidine and hindered phenols) on the enzymic activity of membrane-bound acetylcholinesterase (AChE) was studied. In terms of estimated kinetic characteristics of AChE reaction (KM, Vmax, KI), the pattern of enzyme inhibition by the hindered phenol compounds was found to be of non-competitive or mixed type depending on the inhibitor structure or on the substrate acetylcholine or acetylthiocholine used. The comparative study of the inhibitory action of water-soluble derivatives of hindered phenols and fatty-soluble ionol made it possible to reveal possible contributions to the inhibition of both direct and mediated (by the membrane microsurroundings) effects on the membrane-bound AChE by the studied synthetic bioantioxidants. PMID- 1447419 TI - [The development of the pouch-like structures at the angles of the mouth in the ontogeny of the hamster Phodopus campbelli]. AB - The development of mouth angle sacciform structure was studied in the ontogenesis of hamster Phodopus campbelli. It was found that the true sacciform structure with all components characteristic for adult animals was formed by the 20th day of postnatal development. Histological data have shown than the sacciform structure is formed in ontogenesis as a result of a complex epidermal transformation involving muscular and connective tissues which comprise the external coat. The structure studied is not formed on the basis of sebaceous glands and cannot be assigned to the class of gland as considered before. PMID- 1447420 TI - [The factors influencing the sound activity of forest voles]. AB - The article is devoted to the effect of context on the acoustic activity of bank voles of 4 species (Clethrionomys glareolus, C. centralis, C. rutilus, and C. rufocanus) living in experimental groups. In addition to species differences and social state of a specimen in the group, the acoustic activities of vole is affected by such factors as locomotor activity of the vole itself and its partners (especially dominant ones) and aggression of surrounding voles. PMID- 1447421 TI - [Adaptation to chemical mutagens]. AB - Pre-adaptation of normal and tumor cells to the action of methylnitrosourea was studied. To attain these ends, a single low dose (10 mg/kg) was administered to animals two hours prior to the administration of main therapeutic dose (100 mg/kg) and the number of chromosomal rearrangements was determined. A significant decrease in translocation incidence was observed in metaphases of Ehrlich-ICP ascitic strain. Similar results were obtained on cells of murine bone marrow. The mechanisms of pre-adaptation to the action is discussed. PMID- 1447422 TI - [The qualitative metabolic characteristics of antitumor compounds]. PMID- 1447423 TI - [Hyperautophagy: the pathogenic characteristics of the cells in the Chediak Higashi syndrome]. PMID- 1447424 TI - [The effect of therapy with cytostatics and immunomodulators on mitotic pathology in Lewis tumor cells in mice]. AB - The effect of cytostatics (methylnitrosourea and methotrexate), immunomodulators (thymalin and reaferon) and their combinations on the mitotic pathology of mice Lewis tumour cells was studied. It was revealed that chemotherapy with these agents changed the interrelation between mitotic phases and somewhat enhanced the incidence of pathologic mitoses mainly connected with the damage of mitotic apparatus. Immunomodulators differently affected the cytostatic activity of antitumour agents that may be associated with their mechanisms of action. PMID- 1447425 TI - [Changes in the intensity of protein synthesis in the gastric mucosa following the laser irradiation of a duodenal ulcer]. AB - The intensity of protein synthesis (incorporation/pool) is usually low in normal stomach mucosa and enhanced in exacerbation of peptic ulcer; following the effective laser therapy it decreases only in one third of cases. Therefore the scarring of ulcer not always coincides with the normalization of protein synthesis. The results characterize also the community of reactions in stomach and duodenal mucose membranes. The changes in protein synthesis intensity following the laser irradiation depended neither on the initial size of ulcer nor on the age of patient and the total duration of disease. PMID- 1447426 TI - Completed suicide and recent lithium treatment. AB - Of 1397 completed suicides in Finland in one year, all victims (N = 20) that had used lithium in prophylaxis and treatment of a mood disorder during the three final months were carefully examined. Eight victims (40%) fulfilled the criteria of recent adequate lithium prophylaxis. Continuous or intermittent noncompliance with psychopharmacological treatment during the last two years was reported in the majority (85%) of the victims. Only two cases used lithium as a suicide method. The study suggests that problems especially in compliance but also in quality of treatment are likely to limit the usefulness of lithium treatment in suicide prevention. PMID- 1447427 TI - Characteristics of the Edinburgh Post Natal Depression Scale in The Netherlands. AB - The Edinburgh Post Natal Depression Scale (EPDS), a 10-item self-rating depression scale, was translated into Dutch and compared in 293 postpartum women with other self-rating scales commonly in use in The Netherlands. In addition the structure of EPDS was analyzed by various factor analyses to reveal some of its dimensional aspects. The Dutch version of EPDS was found to be a self-rating scale with good psychometric characteristics which measures what it claims to measure: the strength of depressive symptoms. With LISREL a 2-factor model could be distinguished which contained subscales reflecting depressive symptoms and cognitive anxiety. PMID- 1447428 TI - Unipolar depression: diagnostic inconsistency and its implications. AB - Major depressive disorder using Feighner et al. (Arch. Gen. Psychiatry 26, 57-63, 1972) and DSM-III or DSM-III-R criteria has proven to be a heterogeneous diagnosis. It apparently includes a wide variety of clinical conditions. This report, based upon the results of a multi-year blind follow-up of 500 randomly selected psychiatric outpatients focuses on certain problems associated with the diagnosis of primary unipolar affective disorders. At index, 141 patients received diagnoses of primary unipolar depression. At follow-up, only 62 (44%) of these received the same diagnosis, with an additional 14 (10%) receiving a diagnosis of undiagnosed: questionable primary unipolar depression, and 5 (4%) a diagnosis of bipolar disorder. Thus, about 43% received other diagnoses at follow up: 35 (25%) diagnoses of secondary depression and 25 (18%) other diagnoses without indication of an affective component. Bipolar patients' stability was significantly better for those who were manic at intake. PMID- 1447429 TI - The validity of major depression with atypical features based on a community study. AB - This article reports on evidence for the validity of major depression (MDD) with atypical features (defined as overeating and oversleeping) as a distinct subtype based on cross-sectional and 1-year prospective data from the Epidemiologic Catchment Area study. MDD with atypical features, when compared to MDD without atypical features, was associated with a younger age of onset, more psychomotor slowing, and more comorbid panic disorder, drug abuse or dependence, and somatization disorder. These differences could not be explained by differences in demographic characteristics or by symptom severity. This study, based on a community sample, found that major depression with atypical features may constitute a distinct subtype. PMID- 1447430 TI - Proposed subtypes of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with hyperthymic temperament. AB - In an attempt to improve the classification of Bipolar II disorders, we have examined a consecutive series of 687 primary major depressives: 5.1% gave a past history of mania (Bipolar I), 13.7% met our operational criteria for hypomania (Bipolar II), and the remaining 81.2% were provisionally categorized as 'unipolar.' Although Bipolar II was in some respects intermediate between Bipolar I and Unipolar, gender, familial bipolar history, age at onset and course characteristics generally supported its closer kinship to bipolar illness. Seventy one of the unipolars (10.3% of the total series) further met our operational criteria for hyperthymic temperament (U-HT), leaving behind a purer unipolar group of 487 major depressives. With respect to the proportion having male gender and bipolar family history, U-HT was similar to Bipolar I and II, and all three differed significantly from pure unipolar; as for age at onset, number of episodes and related indices of course, BI and BII were similar, and U-HT was closer to pure unipolar. These findings suggest that major depressive episodes arising from a hyperthymic temperament (constituting 12.4% of the 'unipolar' universe by conventional definition) are 'genotypically' closer to Bipolar II defined by hypomania, and course-wise similar to other unipolars. PMID- 1447431 TI - Prodromal symptoms in panic disorder with agoraphobia: a replication study. AB - The majority of 20 patients suffering from panic disorder with agoraphobia reported experiencing agoraphobic avoidance, generalized anxiety, and/or hypochondriacal fears and beliefs before the first panic attack. The results replicated those of a previous investigation and are in accordance with an increasing number of studies concerned with prodromal symptoms, epidemiologic surveys, and analysis of mechanisms of change upon treatment. PMID- 1447432 TI - The Galway Study of Panic Disorder. II: Changes in some peripheral markers of noradrenergic and serotonergic function in DSM III-R panic disorder. AB - Sixty six patients with panic disorders, fulfilling the DSM III criteria for panic attack, together with a group of age and sex matched controls, were studied for changes in their peripheral noradrenergic and serotonergic status before treatment and during six months treatment with either clomipramine or lofepramine. The results of this study suggest that, despite clinical improvement, the peripheral markers of both adrenergic (platelet aggregation to noradrenaline, platelet alpha 2 receptor density and lymphocyte beta receptor density) and serotonergic (platelet aggregation to serotonin, 3H-ketanserin binding to platelet 5HT2 receptors and 3H-5HT uptake into platelets) function largely remained abnormal. It is concluded that such abnormalities are trait markers of biogenic amine function in patients with panic attack. Further studies are needed to determine whether or not these parameters eventually normalize in those patients showing prolonged remission of symptoms. PMID- 1447433 TI - High prevalence of cobalamin deficiency in elderly outpatients. AB - OBJECTIVE: To measure the prevalence of cobalamin (vitamin B12) deficiency in geriatric outpatients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment. DESIGN: Prospective study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays. In patients with serum cobalamin levels < or = 300 pg/mL, the response to cobalamin treatment in the group with levels of methylmalonic acid and/or homocysteine > 3 standard deviations (SD) above the mean for normals was compared with that of those without such elevations. SETTING: Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center, Denver, CO. PATIENTS: One-hundred and fifty-two consecutive outpatients, ages 65 to 99, were screened. Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospectively evaluated and treated with cobalamin. MAIN OUTCOME MEASURES: Cobalamin, methylmalonic acid, homocysteine, complete blood counts, neurologic examination, and neuropsychological testing. RESULTS: The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and/or homocysteine elevated to > 3 SD was 14.5% of the screened outpatients. A similar proportion of patients with low normal serum cobalamin levels (between 201 and 300 pg/mL) demonstrated elevated metabolites > 3 SD (56%) compared with patients with low serum cobalamin levels (< or = 200 pg/mL) (62%). Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospectively. Results for complete blood count, lactate dehydrogenase, bilirubin, baseline neurologic score, and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites. The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment. One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment. CONCLUSION: There was a high (14.5%) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly outpatients. The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201-300 pg/mL compared with patients with low cobalamin levels (< or = 200 pg/mL) had markedly elevated metabolites which fell with cobalamin treatment. Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects. PMID- 1447434 TI - Attitudes toward discussing life-sustaining treatments in extended care facility patients. AB - OBJECTIVE: To determine nursing home residents' attitudes toward discussing life sustaining treatment plans with their physicians and the factors associated with these attitudes. DESIGN: Random-sample, interviewer-administered survey. SETTING: Forty-one nursing homes in which some residents were cared for by house-staff physicians of the Hennepin County (Minnesota) Medical Center Extended Care Department. PATIENTS: Random sample of 150 nursing home residents receiving primary care from Extended Care Department physicians, 131 (87%) of whom completed the interview. RESULTS: Older individuals were less likely to have spoken with physicians and family members about treatment plans (p < 0.05), and to have felt that they had more say than necessary in their treatment (P < 0.05). Only 19 (14.5%) residents had formal treatment plan discussions about limiting life-sustaining treatment. Although perceived current health status did not differ between residents with and without treatment plans, those residents who had discussions about advance directives were more likely to report health improvement over the past 6 months (P < 0.05). Residents with formal advance directives were, on average, 8.4 years younger than those without them (P < 0.05). CONCLUSIONS: Younger patients are more likely to have had discussions about life-sustaining treatment and are also more frequently involved in plan development. Preferences for level of involvement should be considered during advance directive planning, and it should be recognized that these preferences may vary with age. Future research should evaluate whether this age relationship is a true age or a cohort effect. PMID- 1447435 TI - Prevalence and characteristics of symptomatic gastroesophageal reflux disease in the elderly. AB - OBJECTIVE: To study prevalence and characteristics of symptomatic gastroesophageal reflux disease in the elderly. DESIGN: Survey by questionnaire of stratified random sample. SETTING: City of Turku, Finland. SUBJECTS: Population-based random sample consisting of non-institutionalized subjects aged 65 years or over. A questionnaire was sent to 559 subjects. The response rate was 92%. Twenty-nine incompletely filled forms were rejected. Thus, the questionnaires from 487 subjects, representing 87% of the original number, constitute the basis for the study. MEASUREMENTS: The questionnaire inquired about the following symptoms: heartburn, regurgitation, chest pain, dysphagia, dyspepsia, respiratory symptoms, vomiting, and belching. RESULTS: The age adjusted prevalence of daily symptoms suggestive of gastroesophageal reflux disease was 8% in men and 15% in women (P < 0.05). Fifty-four percent of men and 66% of women reported that they had symptoms at least once a month (P < 0.05). The prevalence of symptoms was roughly the same across age groups. The occurrence of chest pain, dyspepsia, vomiting, belching, dysphagia, chronic cough, hoarseness, and wheezing were associated with symptoms suggestive of gastroesophageal reflux disease. CONCLUSIONS: Symptoms suggestive of gastroesophageal reflux disease are common in elderly subjects. Women suffer from these symptoms more frequently than men. Typical reflux symptoms are often associated with atypical complaints, such as abdominal symptoms, chest pain, or respiratory symptoms. PMID- 1447436 TI - The equivalency of infrared tympanic membrane thermometry with standard thermometry in nursing home residents. AB - OBJECTIVE: To compare the equivalence of infrared tympanic membrane (TM) measure of body temperature with standard electronic oral (PO) and rectal (R) measures in a nursing home population. DESIGN: Randomized repeated-measurement design. METHODS: For the study, 82 randomly selected residents (mean age 79 +/- 10 years) of the Nursing Home Care Unit of the VAMC West Los Angeles had PO, R, and TM temperatures measured before arising (6-8 am). An otoscopic exam and the age, sex, presence of neurologic disease, and compliance with thermometry was noted. Also, repeated measures of PO and TM temperatures were performed three times to assess variability. The Pearson's correlation coefficient was determined for PO versus R and for TM versus R temperatures. Stepwise regression analysis was performed with the dependent variable of R temperature and the independent variables of the mean TM temperature, age, sex, presence of neurologic disease, position of the resident, and extent of ear canal occlusion. RESULTS: The correlation of TM versus R (r = .39, P = .004) was better, though not significantly, than of PO versus R (r = .28, P = .04). TM had less variability than PO (pooled standard deviation .38 vs .45 degrees F, respectively) and TM was implemented successfully more often than PO or R (96% vs 81% vs 81%). CONCLUSION: Therefore, TM was at least equivalent or better than PO measures of temperature in this population. The efficacy of fever detection and the use and durability of long-term use by nursing staff needs to be studied. PMID- 1447437 TI - Nocturia: a risk factor for falls in the elderly. AB - OBJECTIVE: To determine if nocturia is a risk factor for reported falls and bone fractures in older persons. DESIGN: Cross-sectional study comparing falls in men and women with and without nocturia. SETTING: Longitudinal health screening program of ambulatory elderly participants. PARTICIPANTS: Participants included 988 (65.5%) women and 520 (34.5%) men who had completed their tenth annual visit to the program. MAIN OUTCOME MEASURES: Reported falls in the past year and reported bone fractures in the past 5 years. RESULTS: Participants who reported nocturia at least twice during the night were at significantly greater risk to report falls (Odds Ratio = 1.84; 95% CI = 1.05-3.22), and the risk increased in subjects reporting more than three nocturia events (Odds Ratio = 2.15; 95% CI = 1.04-4.44). The significant increase in falls reported by nocturia participants did not result in an increase in reported bone fractures in the past 5 years (P < 0.4360). CONCLUSIONS: Nocturia is an important risk factor for falls in ambulatory elderly persons. Preventive measures should be taken to decrease nocturia events and to decrease the risk of falling during these nocturia events. PMID- 1447438 TI - Bedside assessment of executive cognitive impairment: the executive interview. AB - OBJECTIVE: This study is a pilot validation of the Executive Interview (EXIT), a novel instrument designed to assess executive cognitive function (ECF) at the bedside. DESIGN: Inter-rater reliability testing and validation using inter-group comparisons across levels of care and measures of cognition and behavior. PARTICIPANTS: Forty elderly subjects randomly selected across four levels of care. SETTING: Settings ranged from independent living apartments to designated Alzheimer's Special Care units in a single 537-bed retirement community. MEASUREMENTS: The EXIT: a 10-minute, 25-item interview scored from 0-50 (higher scores = greater executive dyscontrol) was administered by a physician. Subjects were also administered the Mini-Mental State Exam (MMSE) and traditional tests of "frontal" executive function by a neuropsychologist, and the Nursing Home Behavior Problem Scale (NHBPS) by Licensed Vocational Nurses. RESULTS: Interrater reliability was high (r = .90). EXIT scores correlated well with other measures of ECF. The interview discriminated among residents at each level of care. In contrast, the MMSE did not discriminate apartment-dwelling from residential care residents, or residential care from nursing home residents. The EXIT was highly correlated with disruptive behaviors as measured by the NHBPS (r = .79). CONCLUSIONS: These preliminary findings suggest that the EXIT is a valid and reliable instrument for the assessment of executive impairment at the bedside. It correlates well with level of care and problem behavior. It discriminates residents at earlier stages of cognitive impairment than the MMSE. PMID- 1447439 TI - A prospective evaluation of the Geriatric Depression Scale in an outpatient geriatric assessment center. AB - OBJECTIVE: To prospectively evaluate the Geriatric Depression Scale (GDS) in cognitively intact and impaired patients undergoing outpatient geriatric assessment. SUBJECTS: One hundred ninety-four geriatric patients evaluated in a 1 year period. SETTING: The outpatient Geriatric Assessment Center of the University of Nebraska Medical Center. MEASUREMENTS: The 30-item GDS was completed by all patients. The patients were then evaluated by one of three geriatric psychiatrists who were blind to the GDS results. The prospective clinical diagnosis of major depression was compared to the GDS results. Patients were categorized as cognitively impaired or intact on the basis of the Mini Mental State Examination. Data were analyzed using ROC curves. An optimal cutoff was identified which was the total score on the GDS with the highest combined sensitivity and specificity. RESULTS: ROC curve analyses showed good agreement between the clinical diagnosis and the GDS in both cognitively intact and impaired subjects. Cognitively intact, euthymic patients reported a mean of 8.4 symptoms, while cognitively impaired, euthymic patients, reported a mean of 8.7. Cognitively intact, depressed patients reported a mean of 14.7 symptoms, while cognitively impaired, depressed patients reported a mean of 15.0. CONCLUSIONS: This study provides further evidence that the GDS is as accurate a screening test for depression in cognitively impaired as in intact patients. PMID- 1447440 TI - Predictors of two-year post-hospitalization mortality among elderly veterans in a study evaluating a geriatric consultation team. AB - OBJECTIVE: To determine predictors of 2-year post-hospitalization mortality in a cohort of elderly hospitalized patients originally assembled to assess the impact of a Geriatric Consultation Team (GCT). DESIGN: Two-year follow-up of an inception cohort. SETTING: University-affiliated tertiary care VA Medical Center. PATIENTS: One hundred sixty-seven veterans age 75 or older discharged following hospitalization on medical, surgical, or psychiatry services but not intensive care units. INTERVENTION: None specifically studied here though cohort was previously part of randomized control trial of a Geriatric Consultation Team. MEASUREMENT: Mortality during 2 years of post-hospitalization follow-up. RESULTS: Two-year post-hospitalization mortality was 28 percent with no difference between the original GCT and control groups. For the entire sample, age, mental status, admission or discharge ADLs (but not change in ADL status), number of admission problems, number of discharge diagnoses, and discharge site were significant predictors of mortality in univariate analysis. Only discharge ADLs and discharge site remained significant in multivariate analysis. CONCLUSION: Measures of ADLs during hospitalization are stronger predictors of mortality following hospitalization than disease diagnoses. Impaired ADLs and placement other than at home are significant predictors of mortality, suggesting that the decision for nursing home placement contains other independently predictive information within it and/or that the subsequent nursing home period produces excess mortality. As had been indicated in short-term follow-up, there was no survival advantage for the Geriatric Consultation Group. PMID- 1447441 TI - Alcohol abuse in elderly emergency department patients. AB - OBJECTIVES: To determine the prevalence of alcohol abuse in elderly emergency department (ED) patients; to determine the prevalence of alcohol abuse for various categories of illness and injury among these patients; and to determine the frequency of detection of elderly alcohol abusers by ED physicians. DESIGN: Cross-sectional prevalence study. SETTING: The emergency department of a 625-bed university hospital that serves a mixed urban and rural population. PATIENTS: 205 patients aged 65 and over who came to the ED during an 8-week period. MEASURES: A structured interview, which included the CAGE questionnaire and other questions regarding alcohol use, was administered. Emergency department records and past medical records were reviewed. RESULTS: The prevalence of lifetime alcohol abuse (CAGE positive or self-reported drinking problem) was 24%. The prevalence of current alcohol abuse (CAGE positive or self-reported drinking problem and alcohol use within the last year) was 14%. There was a particularly high prevalence (22%) among those presenting with gastrointestinal problems and a surprisingly low prevalence (7%) among those who presented with falls or other trauma. Physicians detected only 21% of the current alcohol abusers. CONCLUSIONS: Alcohol abuse is a prevalent and important problem among elderly ED patients. It is not well detected by physicians in this setting. Alcohol abuse appears to be less common among elderly trauma patients than their younger counterparts, but is very common among patients with gastrointestinal problems. PMID- 1447442 TI - Reported home health agency referrals by internists and family physicians. AB - OBJECTIVE: To evaluate the frequency of home health agency referrals (HHRs) by internists and family physicians. DESIGN: Telephone survey of a randomly selected, nationally representative, stratified physician sample. PARTICIPANTS AND SETTING: One thousand one hundred sixty-one interviews with 576 family physicians and 585 internists selected from the American Medical Association Physician Masterfile. MAIN RESULTS: Most respondents (88%) reported making HHRs (mean for those making HHRs = 43/year). Physicians with > or = 48 annual HHRs (n = 315) reported a mean of 2.6 hours/week in home care telephone management and 2.1 hours/week on related paperwork. Rural internists and family physicians (n = 230) reported less availability of several types of non-physician home health services than non-rural respondents (n = 931), yet rural physicians were more likely to refer patients to home health agencies. Using multivariate linear regression, the reported frequency of HHRs was significantly related to rural practice location, number of home-bound patients, proportion of geriatric patients, number of house calls, graduation from a U.S. or Canadian medical school, physician knowledge of community resources, and physician experience either as a medical director, a member of the board of directors, or a consultant for a home health agency. CONCLUSIONS: Internists and family physicians who work at least 10 hours per week in ambulatory care report making approximately three home health agency referrals per month and spending substantial amounts of time coordinating home health agency care. Despite reporting less availability of many home health agency services, rural physicians report greater involvement than non rural physicians in the delivery of home care. PMID- 1447443 TI - A comparison of patient risk for pressure ulcer development with nursing use of preventive interventions. AB - OBJECTIVE: (1) Determine if the Braden scale or Norton scale predicted the same patients to be at risk for pressure ulcer development as were receiving preventive nursing interventions. (2) Identify the items on the Braden and Norton risk assessment scales that the nurses used intuitively to determine a patient's need for a preventive intervention. DESIGN: Cross-sectional study. SETTING: Six hundred-bed, state-supported, long-term care facility. PATIENTS: War veterans who were 82% male and 97% caucasian, mean age 73. MEASUREMENTS: (1) Patients were categorized as at-risk or not-at-risk by the Norton and Braden scales. (2) The presence of a preventive nursing intervention was noted. Agreement in assignment of at-risk status among the two assessments and presence of a preventive intervention was analyzed using Cohen's Kappa. (3) The staff nurses' use of preventive interventions was modeled using stepwise logistic regression. The items from the Braden and Norton risk assessment scales were used as independent variables with staff nurse implementation of a preventive intervention as the dependent variable. RESULTS: Nurse preventive interventions were found on 45% of patients. The Norton scale identified 38% and the Braden scale identified 27% of patients as at-risk. Agreement among the three methods was 0.53. Agreement between the Braden and Norton scales was 0.73. Agreement between use of a preventive intervention and a classification as at-risk by the Braden or Norton scale was 0.41 and 0.43, respectively. Stepwise logistic regression revealed that low Braden mobility scores (Odds Ratio: 2.74) and low Braden friction/shear scores (Odds Ratio: 3.29) were associated with an increased likelihood of a patient receiving a preventive nursing intervention. CONCLUSIONS: The overall level of agreement among the two scales predicting risk and the presence of a preventive intervention was not high. Agreement, however, between the two risk assessment scales was close. The staff nurses apparently relied on a patients' mobility, their exposure to friction/shear, and additional unidentified factors to guide implementation of a preventive intervention. Further study is needed to define the cost, efficacy, and related cost effectiveness of routine pressure ulcer risk assessment. PMID- 1447444 TI - The influence of treatment descriptions on advance medical directive decisions. AB - OBJECTIVE: To determine whether the wording of the descriptions of life sustaining interventions would affect the choices elderly patients make when completing advance directives. METHODS: Survey. SETTING: General community in Omaha, Nebraska. PATIENTS: Two hundred one community-dwelling elderly were selected from a population-based sample. MAIN OUTCOME MEASURES: Subjects were asked whether they would accept or reject three life-sustaining interventions: cardiopulmonary resuscitation, mechanical ventilation, or tube feeding in three separate hypothetical case scenarios. The three life-sustaining interventions were each described positively, negatively, and exactly as they are worded in a widely used advance directive. Subjects reviewed each scenario three times with three different descriptions of the three interventions. RESULTS: For the three interventions presented in three scenarios, subjects opted for the intervention 12 percent of the time when it was presented negatively, 18 percent of the time when it was phrased as in an advance directive already in use and 30 percent of the time it was phrased positively. One hundred fifty-five of the 201 subjects (77 percent) changed their minds at least once when given the same scenario but a different description of the intervention. Of these 155, 33 percent changed decisions one to three times, 33 percent changed decisions four to seven times, and another 34 percent changed decisions eight to seventeen times based solely on the description of the intervention. CONCLUSION: The decisions patients make about whether to accept or reject life-sustaining treatments are affected by the descriptions of the treatments. These findings emphasize the critical importance of doctor-patient consultation when patients execute advance directives. PMID- 1447445 TI - Probable heterosexual transmission of AIDS in an aged woman. PMID- 1447446 TI - Primary brain tumors in the older patient: an annotated review. PMID- 1447447 TI - Geriatric medicine: how we will fare with the Medicare Fee Schedule. PMID- 1447448 TI - Historical perspective: the neurotrophic theory of skin ulceration. AB - Though nearly forgotten, the neurotrophic theory was very much a part of mainstream medical thinking during the mid-nineteenth century. This theory stated that all bodily organs are maintained by special nutritional factors secreted by the central nervous system. Development of skin ulceration in the face of neurologic injury became a model for the theory, and controversy involved two great neurologists of the time, Jean Martin Charcot and Edouard Brown-Sequard. As the neurotrophic theory fell into disfavor, interest in decubitus ulcers waned as well. Today, pressure sores remain a major epidemiologic problem for the growing population of frail elderly persons in both acute and long-term care settings. Because of the increased mortality, morbidity, and cost associated with these lesions, attention needs to be refocused on research and education concerning the decubitus ulcer. PMID- 1447449 TI - The new Medicare Fee Schedule. PMID- 1447450 TI - The resurgence of free radicals. PMID- 1447451 TI - Influenza A outbreaks in nursing homes. PMID- 1447452 TI - Rhabdomyolysis and the neuroleptic malignant syndrome. PMID- 1447453 TI - A new clinical syndrome: multiple organ failure in the elderly. PMID- 1447454 TI - What will the scope of optometric practice be in the year 2000? AB - For the past 100 years, the scope of optometric practice has been constantly expanding. As the body of knowledge about visual function has increased, new treatment options have been developed. Optometry must accept the professional responsibility for treatment of all conditions of the eye and visual system. By the year 2000, optometry must be prepared with expanded curricula and accountable for the treatment of all visual conditions in order to maintain its place as a primary provider within the health care system. PMID- 1447455 TI - What will the scope of optometric practice be in the year 2000? PMID- 1447456 TI - Should optometry evolve as a vertically integrated discipline that includes all components of ophthalmology? AB - Change in the optometric profession is inevitable. Persuasive economic factors will play a great role in shaping the future of optometry and ophthalmology. Optometry is in a position now and into the future to leverage its great strengths to benefit the public in a cost conscious manner. PMID- 1447457 TI - What are the appropriate skills and knowledge required for the entry-level practice of optometry? AB - All health professions have developed a national program of competence assessment to address the specific issue of "entry-level practice." This is also true in optometry through the 3-Part examinations of the National Board of Examiners in Optometry. These examinations test the cognitive (knowledge) skills necessary to be fit to practice and the communication, affective and psychomotor skills that are required to apply the underlying knowledge in the solution of patient problems. The scope of the National Board examinations and how they change to keep pace with the expansion and the scope of practice, demonstrates that entry level is a dynamic concept. PMID- 1447458 TI - Time for educational reform. AB - As the profession of optometry evolves, complementary changes in the educational process must occur if graduates are to be fully prepared to practice primary eye care. A national conference to address these educational priorities including curriculum design, faculty manpower and financial resources has recently been held. The need for educational reform facing the profession is outlined. PMID- 1447459 TI - The expanding scope of optometry and the impact on the curriculum of schools and colleges. AB - The expansion of the profession of optometry has placed pressures on the schools and colleges of optometry to reduce traditional curricular elements, add new ones, obtain faculty trained for the new scope of the profession, and provide additional patient experiences for hands-on learning. While the schools have adapted to these pressures and are leading the profession into new areas, the traditional 4-year optometry curriculum is critically filled. Further expansion will require difficult decisions. PMID- 1447460 TI - The expanding scope of practice and the optometric curriculum. AB - The expansion of the scope of optometric practice has put tremendous pressures on the curricula of the optometric teaching institutions. The pressures and the solutions that have been proposed in the optometric literature are outlined. The possibility of eliminating portions of the curriculum that have traditionally been regarded as the educational foundation of the practice of optometry and what effect this would have on the very definition of the term "optometry" is discussed. PMID- 1447461 TI - An appropriate patient base for clinical optometric education. AB - The reasons for the need of an expanded patient base for adequate clinical instruction in the 4-year professional program are discussed. Optometric education must establish the "reasonable set" standard for patient size and diversity particularly in view of its expanded scope of professional responsibility. PMID- 1447462 TI - What are the pros and cons of requiring postgraduate residency training as an entry level practice requirement? AB - The technological and knowledge explosion that has occurred in this century has created a curriculum crunch within all health professional schools. The various optometric institutions are dealing with this crunch and important decisions need to be made in order to provide the best entry-level practitioners possible. This paper provides some of the pros and cons of requiring a year of postgraduate training as a requirement for entry level optometry practice. PMID- 1447463 TI - What role will residency education take in the profession by the year 2000? AB - Residency education has enjoyed relatively slow but steady growth since its inception in the mid-1970s. A certain segment of recent graduates consider graduation from optometry school as entry level and perceive the need for additional clinical education. The creation of new residency programs and the expansion of existing ones may occur in a variety of settings. For residency education to realize its full potential, optometry must seek federal support for post-graduate clinical education. This would be consistent with federal support provided to other professions for the support of post-graduate clinical education. PMID- 1447464 TI - What role will residency education take in the profession by the year 2000? AB - There is a need to expand the number of optometric residencies to meet the current increased demand from graduates seeking to fill the expanding number of residency positions, as well as the projected needs of the profession for the 21st century. Supportive rationales and recommendations for potential development of residencies are discussed. PMID- 1447465 TI - The need to incorporate professional principles, attitudes and ethics in optometric education. AB - This paper reviews the development of ethical principles for the profession of optometry over the past 90 years, and how these principles have been modified and expanded in conjunction with the scope of practice during that period. The author discusses the mandated principles of licensing boards as well as Medicare and Medicaid requirements. In addition, areas of "non-mandated" ethical principles are reviewed such as the aging and AIDS patient, over testing, continuing education, corporate employment, patient records and referrals. The author suggests that ethical issues should be incorporated into all optometric courses in the curriculum and not just in a specific ethics course in order that many role models offer their input to students in the development of an ethical model for their professional lives. PMID- 1447466 TI - The need to incorporate professional principles, attitudes and ethics in optometric education. AB - It is vital to the continued independence of optometry for its practitioners to exude professionalism. Professional principals, attitudes and ethics must be incorporated into the curriculum of optometric education at the earliest possible time and be reinforced by lesson and example throughout the educational experience. PMID- 1447467 TI - How can the optometric profession expand the pool of qualified applicants? AB - The American Optometric Association and the Association of Schools and Colleges of Optometry need an aggressive public awareness campaign to encourage an increase in the pool of qualified applicants for a career in optometry. One of the most significant ways an individual AOA member can impact this process is to serve as role model for potential applicants. PMID- 1447468 TI - How can the optometric profession expand the pool of qualified applicants? AB - The health professions, including optometry, are facing a declining applicant pool. The American Optometric Association has taken steps to address the challenge of increasing the pool of qualified applicants to the schools and colleges of optometry. However, the most significant factor in the process will be the efforts of individual AOA members. PMID- 1447469 TI - How can optometry become more effective in recruiting and retaining appropriate numbers of underrepresented and disadvantaged students. AB - The proportion of minority students in optometry schools remains very small compared to that in the general population. The numbers in the general population are rising and the gap could widen if serious recruitment programs are not implemented. The most effective methods of expanding the applicant pool and recruiting students involve personal contact with people in the profession. Admissions processes must be carefully analyzed to eliminate systematic bias. Retention programs should be in place and can also be used to benefit all students. Financial aid programs must be expanded to accommodate a higher proportion of students from lower socio-economic backgrounds. PMID- 1447470 TI - Why should optometric research be designated as a priority for the profession? AB - Research is the discovery of new information, ideas or theories that increases our knowledge and understanding of ourselves and our environment. Optometric research focuses on the health, functioning and performance of people with emphasis on their eyes and vision. The goal of optometric research is to enable optometrists to provide high quality eye and vision care for their patients. PMID- 1447471 TI - What should be the proper size and number of optometric schools? AB - The Health Professions Educational Assistance Act brought infusion of millions of dollars into optometric education at a time when the profession was ill prepared with inadequate space standards and cost studies. The profession presently faces the need to make major curricular changes at a time of severely constricted resources. Optometry, in a dynamic mode, needs to establish acceptable standards consistent with the profession's demands and goals for the 21st century. PMID- 1447472 TI - Student indebtedness and practice mode choice. AB - Student indebtedness upon graduation from optometry school has long been cited as the major factor influencing practice mode choice. A review of the literature, practice trends for optometry, medicine and dentistry, and forces affecting the health care industry reveal other factors as well. PMID- 1447473 TI - The recruitment and retention of disadvantaged and underrepresented groups in optometry. AB - The recruitment and retention of disadvantaged students represents a formidable challenge to optometric educators. Referrals by optometrists and counsellors, visits to minority campuses, and information through the news media can help the recruitment process. Academic achievement and retention rates can be enhanced by tutorial programs, development of learning centers, learning modules, self-paced materials, and computer software. The most important element is the sensitivity of faculty and administrators to the educational needs of the students and the health care needs of disenfranchised populations. PMID- 1447474 TI - Basis for body weight exponent (0.75) as a scaling factor in energy metabolism and risk assessment. AB - The basis that led to the adoption of the exponent (0.75) as a scaling factor for the relationship between body weight and energy metabolism is presented. In the risk assessment formulation, it may be appropriate to use the 0.75 power of body weight as a scaling factor for carcinogenicity data obtained from animal studies. PMID- 1447475 TI - One-year toxicity of orally administered acrolein to the beagle dog. AB - Forty-eight dogs were separated into four groups of six males and six females. Acrolein (0.1% aqueous) was administered in gelatin capsules to three of these groups at dosing levels of 0.1, 0.5 and 1.5 mg kg-1 day-1 based on results of a range-finding study. After 4 weeks, the high dose was increased to 2 mg kg-1 day 1. The fourth group received deionized water in the same number of gelatin capsules as the high-dose group. Dosing was 7 days per week for 53 weeks. Blood and biochemical measurements were made pretest and at 3-month intervals thereafter. At termination, all dogs were subjected to full necropsy and histological examination. The major test effect noted was frequent vomiting after dosing. This was observed to be dose-dependent and the frequency decreased with time, indicating an adaptive effect. One mid-dose female died during the test and was diagnosed as having died of severe bronchial pneumonia, probably a result of vomitus aspiration. Serum albumin, calcium and total protein values were depressed in high-dose animals throughout the study. Some variability in red blood cell parameters and coagulation times were noted but the significance of these effects was not obvious. PMID- 1447476 TI - Variable effects of chemical allergens on serum IgE concentration in mice. Preliminary evaluation of a novel approach to the identification of respiratory sensitizers. AB - A wide variety of chemicals may induce allergic contact dermatitis (contact sensitivity). Some chemical allergens may, in addition, cause respiratory sensitization. Topical exposure of mice to contact and respiratory chemical sensitizers results in the initiation of divergent immune responses characteristic of preferential activation of different functional subpopulations of T helper (TH) cells. In the present study we have sought to make use of these differences, particularly differences in the ability of contact and respiratory allergens to provoke IgE responses, and to question whether opportunities exist for the identification of chemicals with the potential for respiratory sensitization. We have examined alterations in the serum concentration of IgE following topical exposure of mice to seven chemical allergens; trimellitic anhydride (TMA), phthalic anhydride, diphenylmethane-4,4'-diisocyanate (MDI), dicyclohexylmethane-4,4'-diisocyanate (HMDI), isophorone diisocyanate (IPDI), oxazolone and 2,4-dinitrochlorobenzene (DNCB). Three of these--TMA, phthalic anhydride and MDI--are known human respiratory sensitizers. The other four--HMDI, IPDI, oxazolone and DNCB--appear not to cause respiratory allergy, or at least have a very limited potential to do so. At the concentrations tested, exposure to all chemicals caused a lymphocyte proliferative response in lymph nodes draining the site of application. However, exposure only to TMA, phthalic anhydride and MDI resulted in a substantial increase in the concentration of serum IgE. Treatment with HMDI and IPDI failed to induce any change in serum IgE concentration. DNCB and oxazolone caused only small and transient elevations of IgE that were considerably less marked than those observed with respiratory sensitizers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447477 TI - Toxicity of 2-methyl-5,6-cyclopentapyrimidine (MCPP). AB - 2-Methyl-5,6-cyclopentapyrimidine (MCPP, CAS No. 36274-29-0) is a white dusty solid with a powerful lingering odor and is formed as a by-product in the polymer synthesis of an experimental polymer. The acute toxicity following both oral and inhalation exposures and the effects of repeated inhalation exposures in rats were determined. Mutagenic activity was assessed using Salmonella as the indicator organism. The chemical is moderately toxic, with the lethal dose following a single oral administration being 90 mg kg-1. Doses greater than or equal to 130 mg kg-1 produced strong convulsions. Excessive salivation, hyperactivity and twitching were seen at 90 mg kg-1 and only mild initial weight loss was seen in surviving rats (less than or equal to 60 mg kg). Liver injury was produced at doses as low as 17 (but not at 12) mg kg-1. The material was highly toxic by inhalation, with the approximate lethal concentration in rats following single 4-h exposures being 9 ppm. Convulsive-like movements were seen at greater than or equal to 9 ppm (not at 2 ppm). Histological findings suggest that MCPP causes dilation of blood vessels with hyperemia of various organs apparent in rats exposed to 1 ppm and sacrificed 1 or 2 days post-exposure. No evidence of liver or central nervous system damage was seen. Repeated (nine daily 4-h exposures) inhalation of 2 ppm MCPP failed to produce any signs of a toxic response. No mutagenic activity was seen. The material needs to be considered as a potent acute toxin. PMID- 1447478 TI - Calcium antagonists can be classified using in vitro toxicity and potency indices. AB - The toxicity of eleven calcium antagonists from different chemical families was determined in rat hepatocyte primary cultures. The calcium antagonist potency of the same compounds was also determined in isolated rabbit aortic rings contracted with high K+. The hepatocytotoxicity of the calcium antagonists was not directly linked to blockade of voltage-operated calcium channels, since there was no correlation between the rank order of hepatotoxicity and that for calcium antagonist potency. The toxicity and calcium antagonist potency of each calcium antagonist examined were used to calculate an in vitro therapeutic index value for each compound. It was observed that therapeutic indices fell into three distinct groups and we therefore propose that the in vitro therapeutic index can be used to subclassify the calcium antagonist group of drugs. The proposed classification corresponds very closely with one already suggested by Spedding on pharmacological grounds. In conclusion, the in vitro therapeutic index may provide a useful tool in the characterization and subclassification of novel calcium antagonist compounds. PMID- 1447479 TI - Effect of single gallium arsenide exposure on some biochemical variables in porphyrin metabolism in rats. AB - Gallium arsenide (GaAs) inhibited, dose dependently, delta-aminolevulinic acid dehydratase (ALAD) activity in blood (as observed on days 1, 7 and 15), liver and brain (on day 15) after a single oral treatment. Levels of blood zinc protoporphyrin (ZPP) and urinary delta-aminolevulinic acid (ALA) excretion were elevated on day 7 and day 15 following exposure to 2000 mg kg-1 GaAs. A dose dependent increase in blood As contents was observed while blood Ga was detectable only at higher doses. PMID- 1447480 TI - Alteration of brainstem auditory evoked potentials in diethylbenzene and diacetylbenzene-treated rats. AB - Male Sprague-Dawley rats were treated either with 1,2-diethylbenzene (1,2-DEB) or its putative active metabolite, 1,2-diacetylbenzene (1,2-DAB). Experimental rats and appropriate controls were examined electrophysiologically for brainstem auditory evoked potentials (BAEP). Oral administration of 1,2-DEB (75 or 100 mg kg-1 once a day, 4 days a week, for 8 weeks) and intraperitoneal injection of 1,2 DAB (10 or 15 mg kg-1 once a day, 4 days a week, for 8 weeks) produced time- and dose-dependent increases in the peak latencies of all BAEP components as well as in interpeak (I-V) differences, and a decrease in the amplitudes of all the components. The absolute and interpeak latencies recovered partially during an 8 week (1,2-DEB) or a 10-week (1,2-DAB) recovery period, whereas there were long lasting decreases in peak amplitudes. PMID- 1447481 TI - The Ca(2+)-transport-ATPase of human erythrocytes as an in vitro toxicity test system--acute effects of some chlorinated compounds. AB - Investigations to determine the inhibitory activity on the Ca(2+)-transport ATPase of human erythrocyte membranes were performed with various compounds of toxicological significance, mostly chlorinated and mainly used as biocides, such as phenol, 4-chlorophenol, 2,4-dichlorophenol, 2,6-dichlorophenol, 3,4 dichlorophenol, 2,3,4-trichlorophenol, 2,3,4,5-tetrachlorophenol, pentachlorophenol (PCP), captan, folpet, captafol, (+)-camphene, toxaphene, dichlorodiphenyltrichloroethane (DDT), lindane, endrin, dieldrin, alpha endosulfan, beta-endosulfan, paraquat, diallate, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Some of the compounds investigated display an inhibitory effect on the Ca(2+)-transport-ATPase at very low concentrations. The in vitro results obtained in this enzyme assay can be correlated directly with the results of other in vitro assays and with the results of in vivo investigations in different species in which an inhibitory effect on various biological functions is observed. Therefore, an inhibitory effect on the Ca(2+)-transport-ATPase indicates a toxic effect of these compounds to cell functions. Since the inhibitory effect of these compounds can be measured rapidly and the enzyme is easy to handle, it might be a useful tool to screen the toxic effects of various compounds on cell function. The aim of the authors was to investigate the usefulness of this screening test system for the characterization of the cellular toxicity of various compounds. PMID- 1447482 TI - Haematological and hepatotoxic effects of silken styles of corn in albino rats. AB - The alterations of haematological parameters in albino rats were studied after oral administration of an aqueous extract of silken styles of corn (Zea maize Linn.) at 50, 100 and 150 mg kg-1 daily for 21 days. The following haematological values were significantly reduced on the 7th and 21st day following extract administration: haemoglobin (Hb), red blood corpuscles (RBC), clotting time (CT), mean corpuscular volume (MCV), haematocrit (Ht), serum glucose, blood urea nitrogen (BUN), cholesterol, aspartate transaminase (AST), alanine transaminase (ALT), calcium, total protein, total albumin and total acid phosphatase; and white blood corpuscles (WBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), alkaline phosphatase and creatinine increased. The remaining parameters were not significantly affected, except body weight parameters at the two highest doses. The results emphasize that the biochemical changes caused through aqueous extract of silken styles of corn (Zea maize Linn.) are not significantly toxic at low and medium doses (50 and 100 mg kg-1). PMID- 1447483 TI - Changes in lipid peroxidation levels and lipid composition in the lungs, livers, kidneys and brains of mice treated with paraquat. AB - We examined lipid peroxide levels and the lipid composition of homogenates prepared from the lungs, livers, kidneys and brains of 48 male ICR mice treated with 30 mg kg-1 paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride). The mice were divided into eight groups, in which they were killed 0, 1.5, 3, 6, 12, 24, 48 and 120 h after the administration of paraquat. A significant increase in the lipid peroxide level was identified only in the liver. Change in lipid composition was identified in all the examined organs. However, the change was not a characteristic one in which there is a selective decrease of polyunsaturated fatty acids which become degraded in a lipid peroxidation reaction. It is possible that the mechanism of paraquat toxicity may differ in different organs. PMID- 1447484 TI - ATP-MgCl2 increases cisplatin toxicity in the dog and rat. AB - The purpose of this study was to examine if ATP-MgCl2, an agent that protects against acute cisplatin toxicity in vitro, protected against cisplatin toxicity in vivo. Baseline renal function measurements were obtained on dogs (n = 12) and rats (n = 20) on day -1. Dogs were given 90 mg m-2 cisplatin (n = 5), 90 mg m-2 cisplatin and 50 mumol kg-1 ATP-MgCl2 (n = 5), or 90 mg m-2 cisplatin and 150 mumol kg-1 ATP-MgCl2 (n = 2), in a slow bolus i.v. injection on day 0. Rats were given 4 mg kg-1 cisplatin i.p. (n = 6) and 25 mumol kg ATP-MgCl2 (n = 8) i.v. or 4 mg kg-1 cisplatin i.p. and 25 mumol kg-1 ATP-MgCl2 (n = 6) i.v. on day 0. Renal function was assessed on a routine basis for 14 days. All dogs had significantly decreased creatinine clearance following cisplatin administration. There were no significant differences in renal function tests between groups of dogs. One dog given 50 mumol kg-1 ATP-MgCl2 and both dogs given 150 mumol kg-1 ATP-MgCl2 in addition to cisplatin developed acute anuric renal failure and were euthanatized prior to completion of the study. Rats given 4 mg kg-1 cisplatin and 25 mumol kg 1 ATP-MgCl2 had significantly increased blood urea nitrogen and serum creatinine after drug administration, compared to rats given cisplatin alone. The results indicated that ATP-MgCl2 worsened in vivo cisplatin renal toxicity in the dog and rat. PMID- 1447485 TI - Mutagenicity evaluation of riot control agent o-chlorobenzylidene malononitrile (CS) in the Ames Salmonella/microsome test. AB - o-Chlorobenzylidene malononitrile (CS), a riot control agent, was evaluated for its possible mutagenic activity in the Ames Salmonella/mammalian microsome mutagenicity test. Five histidine-deficient (His-) mutant tester strains of Salmonella typhimurium--TA97a, TA98, TA100, TA102 and TA104--were used. The liquid preincubation procedure was used with metabolic activation (presence of S9 mixture) and without metabolic activation (absence of S9 mixture). For the experiments with metabolic activation, three different concentrations of S9 fraction (supernatant of Aroclor 1254-induced rat liver homogenate at 9000 g)- 5%, 15% and 30% in S9 mixture--were used. Along with mutagenic activity, CS was also evaluated for cytotoxic activity in all the five tester strains of Salmonella typhimurium, both in the presence and absence of S9 mixture. The mutagenic and cytotoxic activities of CS were assessed by counting the His+ revertant colonies and by counting the microcolonies (His-, auxotrophs in the background lawn), respectively, and the respective mean values were compared with the relative negative (solvent) control. A dose range of 12.5-800 micrograms plate-1 for CS did not induce a mutagenic response either in the presence or absence of S9 mix. No change in the negative mutagenic response of CS has been observed even in the presence of an elevated level of S9 fraction in the S9 mix. A dose of 200 micrograms plate-1 for CS was found to be cytotoxic by decreasing the surviving cells as well as His+ revertant colonies; however, the effect was reduced in the presence of an elevated level of S9 fraction in the S9 mix. PMID- 1447486 TI - Conventional and new diagnostic applications of a two-site immunochemiluminometric assay for parathyroid hormone. AB - This investigation was carried out to evaluate the clinical utility and diagnostic value of serum intact PTH measurement using a recently introduced immunochemiluminometric assay (ICMA). Studies were carried out in 42 normal subjects, 24 patients with primary hyperparathyroidism, 21 patients on chronic maintenance hemodialysis, 8 patients with postsurgical hypoparathyroidism, 7 patients with cancer hypercalcemia and 6 patients with osteomalacia. A good correlation was found in normal subjects between serum ICMA PTH levels and both intact PTH measured by a two-site immunoradiometric assay (n = 42, r = 0.67, p less than 0.001) and a widely used midmolecule radioimmunoassay (n = 21, r = 0.78; p less than 0.001). Similar good correlations were found in primary hyperparathyroidism patients (IC-MA vs immunoradiometric assay r = 0.74; p less than 0.001; ICMA vs midmolecule assay r = 0.77; p less than 0.001). As far as the hypercalcemic conditions were concerned, in 5 patients with mild primary hyperparathyroidism, ICMA PTH levels were in the upper range of those found in normal subjects, even though they were inappropriately high in respect to serum calcium values. However, serum ICMA PTH levels were clearly suppressed or undetectable in the majority of patients with cancer hypercalcemia or postsurgical hypoparathyroidism. Following calcium and EDTA infusions in patients with primary hyperparathyroidism, the behaviour of ICMA PTH levels in general parallelled that of immunoradiometric PTH assay, thus indirectly suggesting the ability of the method to measure the intact molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447487 TI - Serum concentrations of osteocalcin in patients with hyperthyroidism, hypothyroidism and subacute thyroiditis. AB - Serum concentration of osteocalcin (OC) was measured in sera from untreated patients with Graves' disease, hypothyroidism due to Hashimoto's thyroiditis, and subacute thyroiditis. Serum concentration of OC in Graves' disease and hypothyroidism were 14.1 +/- 5.6 micrograms/L and 3.8 +/- 2.7 micrograms/L, respectively which were significantly different from that of healthy subjects (Graves' disease, p less than 0.001, hypothyroidism, p less than 0.01). Serum concentration of OC in patients with subacute thyroiditis was 8.0 +/- 3.5 micrograms/L which was not statistically different from age-matched normal controls. Serial measurement of serum OC for 24 mo in 15 patients with Graves' disease after initiation of antithyroid drugs disclosed that the decline of serum OC was obtained only 24 mo after antithyroid drug therapy. On the other hand, in hypothyroid patients, increased serum OC was observed after 1-2 months treatment of L-T4. Correlation coefficients between serum concentrations of OC and T3, T4, FT3 or FT4 in all the patients with thyroid disorders were 0.66, 0.51, 0.50 and 0.54, respectively, which were statistically significant (all, p less than 0.001). These results suggest that osteoblastic activity is enhanced in hyperthyroidism and suppressed in hypothyroidism. In hyperthyroid patients, despite of normalization of FT4 concentration in relatively short period (within 3-4 mo), it took 24 mo after initiation of antithyroid drugs for OC to normalize, suggesting not only thyroid hormone per se but also some unknown factor(s) participates in serum OC secretion. In contrast to thyrotoxic patients, rapid increase in serum OC after initiation of supplemental L-T4 treatment in hypothyroidism was observed, suggesting a direct effect of thyroid hormone on the osteoblasts in patients with hypothyroidism. PMID- 1447488 TI - Lack of correlation between sex hormone binding globulin, adrenal and peripheral androgens in precocious adrenarche. AB - Sex hormone binding globulin (SHBG) is a specific steroid-binding plasma glycoprotein regulated by several different factors. Sex steroids are currently considered to be the main physiological regulators of this protein. Testosterone (T) in adults seems to be the main hormone active in lowering SHBG. The role of dihydrotestosterone (DHT) in such regulation, particularly in the prepubertal age, is not well understood, and no data exist about the role of 3 alpha androstanediol (3A alpha) and its glucuronide. In adulthood, in addition to T, 5 ene steroids seems to play a role in the regulation of SHBG plasma concentration. To assess the effect of adrenal and peripheral androgens in modulating SHBG levels in the prepubertal age, we studied subjects with precocious pubarche secondary to precocious adrenarche (PA). PA represents, in fact, a good model of study as it is characterized by an increased production and action of adrenal androgen in females under 8 yr of age and in males under 9. Sixty-five subjects (55 females and 10 males; chronologic age: 3.6 - 8.2 yr (6.9 +/- 1.3, SD); bone age: 3.6 - 11 yr (7.6 +/- 1.9); BMI 17.9 +/- 3 kg/m2) were studied. Fifteen age matched normal children (BMI 15.2 +/- 0.8 kg/m2) were studied as controls. Androstenedione (A), dehydroepiandrosterone (DHA) and its sulphate (DHA-S), T, DHT, 3Ad and its glucuronide (3AG) and SHBG were evaluated in all subjects. In PA cases serum SHBG levels (50 +/- 27 nM) were significantly lower (p less than 0.05) with respect to normal prepubertal patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447489 TI - The effect of iodine on lipid peroxidation and ultrastructure in the thyroids of BB/Wor rats. AB - There has been recent data suggesting that iodine potentiates lymphocytic thyroiditis (LT) by inciting oxidative stress. However, the mechanism by which iodine induces LT in genetically predisposed animals is unknown. This study was undertaken to examine LT-prone BB/Wor (LT-P) rat thyroids for signs of acute iodine toxicity and oxidative damage before the onset of spontaneous LT. Lipid peroxidation was assessed by the measurement of malonyldialdehyde (MDA) in thyroid homogenates after randomization to a treatment group receiving 0.05% iodide in the drinking water or tap water for 24 hours. Basal MDA levels were higher in LT-prone rat thyroids than Wistar rat thyroids, but iodine treatment did not influence intrathyroidal MDA levels. Electronmicroscopy demonstrated that prolonged treatment with excess iodine, increased the number of apical lysosomes. But there were no ultrastructural changes unique to LT-P rat thyroids. These data suggest that although LT-P rat thyroids may experience subclinical oxidative damage before the onset of histologically demonstrable LT, this activity is not affected by iodine. PMID- 1447490 TI - Effects of opioid receptor blockade on luteinizing hormone (LH) pulses and interpulse LH concentrations in normal women during the early phase of the menstrual cycle. AB - To determine the role of endogenous opioid peptides in regulating pulsatile luteinizing hormone (LH) release in the early follicular phase of the menstrual cycle of eumenorrheic women, we evaluated serum LH concentrations in blood collected every 10 min for 12 h in 27 women each studied during two menstrual cycles: (1) without pretreatment and (2) following oral administration of naltrexone, a mu opiate receptor blocking agent, at a dose of 1.0 mg/kg. Pulsatile LH release was assessed by the CLUSTER algorithm. The mean (+/- SE) integrated serum LH concentration (IU/L/min) increased following the administration of naltrexone (4715 +/- 298) in comparison to the control day (3997 +/- 381; p = 0.0008). The mean number of LH pulses (/12 h) detected on the naltrexone day (10.3 +/- 0.3) was higher than on the control day (8.9 +/- 0.4; p = 0.0068). Mean maximal LH peak height (IU/L) was greater on the naltrexone (7.8 +/- 0.5) vs control (6.7 +/- 0.5) days (p = 0.0064) as was the interpulse valley mean serum LH concentration (IU/L; 6.3 +/- 0.4 vs 5.0 +/- 0.4; p = 0.0013). No difference was noted in the mean incremental LH pulse amplitude (IU/L; 1.9 +/- 0.1 vs 2.1 +/- 0.1; p = 0.13), or peak duration (min; 40 +/- 1.8 vs 45.0 +/- 2.4; p = 0.06). Mean LH peak area (IU/L/min) was greater on the control (45.0 +/- 2.4) vs naltrexone (40 +/- 1.8) days (p = 0.0475).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447491 TI - Expression of calcitonin gene-related peptide in medullary thyroid cancer. AB - We studied the expression of calcitonin (CT) and calcitonin gene-related peptide (CGRP) in 18 patients with medullary thyroid cancer (MTC) in the neoplastic (primary or metastatic) tissue by immunohistochemistry and in the plasma by radioimmunoassay. CT immunoreactivity was found in 100% of the primary and metastatic MTC, CGRP was expressed in 66% of the primary tumors and in 73% of the metastases. Both the number of positive cells and the degree of staining were always higher for CT than for CGRP staining. While plasma CT concentrations were always increased in patients with metastases, 3 patients with metastases had undetectable plasma CGRP levels. A positive correlation was found between plasma CT and CGRP levels. These data indicate that CGRP is frequently expressed in MTC sections and that plasma CGRP measurement is an additional marker for MTC, although has no advantage with respect to CT measurements in monitoring the progression of the disease. PMID- 1447493 TI - Interleukin-6 in liver diseases. PMID- 1447494 TI - Proliferation and phenotypic expression of perisinusoidal cells. PMID- 1447492 TI - Improvement of metastatic endocrine tumors of the pancreas by hepatic artery chemoembolization. AB - We report the results of transcatheter intraarterial perfusion of liver with the emulsion of iodized oil and cytostatics performed as palliative treatment in three patients with hepatic metastases of pancreatic endocrine tumors. Two patients had insulinoma and one patient had glucagonoma. They were also treated by medical therapy from the time the diagnosis was made. Intraarterial perfusion of the liver was achieved by Lipiodol emulsified with streptozotocin and 5 fluorouracil. Regarding these three patients therapeutic responses were different in duration of hormone secretion decrease. Relief of hypoglycemic attacks and a significant decrease of plasma immunoreactive insulin concentration within 12 months without any additional therapy was observed in the patient with insulinoma (case no. 2). This patient had slightly increased immunoreactive glucagon concentration from the time of diagnosis. A decrease of immunoreactive insulin levels in other patient with insulinoma and an increase in plasma glucose to the euglycemic range during two months allowed a reduction of doses of somatostatin analogue and diazoxide. Due to rapid progression of the disease, intraarterial perfusion of liver was repeated three months later with the same results. Remission of symptoms was partial in the case of glucagonoma. Immunoreactive glucagon levels were not changed and there was no significant benefit of the treatment. Intraarterial perfusion of liver with iodized oil and cytostatics could be an effective, safe and repeatable method of palliating symptoms of malignant pancreatic tumors, especially in inoperable but nonterminal cases. It could allow reduction of additional medical therapy, but success of the treatment is not predictable. PMID- 1447495 TI - Long-term follow-up study of adult patients with non-cirrhotic obstruction of the portal system: comparison with cirrhotic patients. AB - Thirty-two patients with non-cirrhotic portal system obstruction and oesophageal varices of non-malignant etiology were recruited over 13 years. Diagnosis was based on the presence of oesophageal varices at endoscopy, minor alterations in liver function tests and liver histology, a low hepatic venous pressure gradient, and pertinent angiographic patterns. Twenty-three had portal vein thrombosis, nine had splenic vein thrombosis. Twenty-one had idiopathic portal vein obstruction, 11 had secondary obstruction. The outcome was compared with a group of 32 patients with cirrhosis and portal hypertension, matched for age, Child Pugh class, previous history of gastrointestinal bleeding, and size of oesophageal varices. Patients with non-cirrhotic obstruction of the portal system were followed for up to 171 months (mean 94 months). During follow-up ten patients had gastrointestinal bleeding, and eight died (five of gastrointestinal bleeding). After 6 years of follow-up, the cumulative risk of gastrointestinal bleeding was 24%, the cumulative risk of death was 17%, and the cumulative risk of death from gastrointestinal bleeding was 14%. Cumulative probability of death by any cause and the probability of gastrointestinal bleeding were significantly lower in patients with non-cirrhotic obstruction of the portal system than in patients with cirrhosis comparable for liver function and portal hypertension (p = 0.04 for both). The cumulative probability of death by gastrointestinal bleeding was not significantly different. In conclusion, the prognosis for non cirrhotic obstruction of the portal system is significantly better than for patients with cirrhosis with comparable levels of liver function impairment and severity of portal hypertension. PMID- 1447496 TI - Magnetic resonance imaging and assessment of liver iron content in genetic hemochromatosis. AB - Computed tomography (CT) scanning is not highly sensitive in the assessment of liver iron content and magnetic resonance imaging (MRI) appears to be more efficient. The aim of this study was to determine the effectiveness of MRI in the evaluation of liver iron content using a standard spin-echo technique. The study included 23 patients with genetic hemochromatosis and 24 non-iron-overloaded patients as controls. A comparison was made of: (a) MRI signal intensity of liver, spleen, paravertebral muscles and subcutaneous adipose tissue using two different spin-echo sequences (SE 500/28; SE 2000/28,56); (b) liver attenuation determined by a single energy CT scan; and (c) a biochemical determination of hepatic iron. There was a significant decrease in liver signal intensity in the genetic hemochromatosis group (256 +/- 201, mean +/- S.D.) compared with the control group (801 +/- 413, p less than 0.001), but there was no correlation with liver iron concentration. However, such a correlation was found and was even more highly significant than in CT when the ratio between the liver and another organ was taken into account. For a lower limit of liver/spleen ratio calculated at 0.46 (mean 2 S.D. in the control group), the specificity (0.96) of MRI was satisfactory, but the sensitivity (0.78) remained insufficient (MRI being unable to detect an iron overload of up to 125 mumol/g). Hopefully, these results might be improved in the near future by using more sensitive sequences such as gradient echo sequences. PMID- 1447497 TI - The pathogenesis of vacuoles produced in rat and mouse liver cells by a conjugate of adenine arabinoside monophosphate with lactosaminated albumin. AB - A conjugate of adenine arabinoside monophosphate with lactosaminated albumin produced vacuoles in hepatic cells of rats and mice when given at doses 5-10 times higher than that (35 mg/kg) capable of inhibiting hepatitis B virus replication in patients with chronic hepatitis B. The vacuoles were due to the swelling of secondary lysosomes probably caused by incapacity of the lysosomal enzymes to rapidly digest large amounts of conjugate into products able to cross the lysosomal membrane. Although vacuoles progressively disappeared when conjugate administration was discontinued, the present observation suggests caution in giving the conjugate to man at daily doses higher than 35 mg/kg. PMID- 1447498 TI - Effects of theophylline on hemodynamics and tissue oxygenation in patients with cirrhosis. AB - Since adenosine may play a role in the hyperdynamic circulation of cirrhosis, we examined the effects of theophylline (an adenosine receptor antagonist) on systemic and splanchnic hemodynamics, tissue oxygenation and sympathoadrenal activity in patients with cirrhosis and liver failure. Theophylline (aminophylline) was administered intravenously for 30 min. Six patients received a dose of 3 mg/kg and eight others a dose of 6 mg/kg. The low dose caused plasma theophylline concentrations of 7.4 +/- 1.8 mg/ml (mean +/- S.E.), and induced a significant increase in heart rate from 84 +/- 5 to 93 +/- 8 beats/min. This dosage did not significantly change other hemodynamic values, oxygen (O2) consumption, or sympathoadrenal activity. The high dose elicited plasma theophylline concentrations of 15.8 +/- 4.0 mg/ml. This dose significantly increased heart rate from 78 +/- 5 to 87 +/- 7 beats/min and significantly decreased right atrial pressure from 2.5 +/- 1.0 to 1.4 +/- 0.8 mmHg, stroke volume from 52 +/- 3 to 47 +/- 5 ml.beat-1.m-2 and systolic arterial pressure from 140 +/- 5 to 129 +/- 6 mmHg. In contrast, O2 consumption, sympathoadrenal activity, and all other hemodynamic values (including azygos blood flow) were not significantly modified. As a result, we conclude that, in patients with cirrhosis, theophylline may cause decreased stroke volume which lowers systolic arterial pressure. In our patients theophylline also had a positive chronotropic effect but no vasoconstrictor effect on systemic and splanchnic circulation. Finally, theophylline did not improve tissue oxygenation in patients with cirrhosis. PMID- 1447499 TI - Disseminated intravascular coagulation in liver cirrhosis. AB - We measured thrombin-antithrombin III complex (TAT), soluble fibrin (SF) and D dimer levels in 51 patients with liver cirrhosis to determine whether these tests provide new evidence for the presence of disseminated intravascular coagulation (DIC) in liver cirrhosis. TAT levels (median, range) were increased in the patient group (4.2 micrograms/l, 1.8-60.0) compared to the reference group (2.0 micrograms/l, range 1.5-7.6 micrograms/l). SF levels (0 nmol/l, range 0-80 nmol/l) were also increased in the patients as compared to the controls (0 nmol/l, 0), but there was no correlation between TAT and SF levels (r = 0.23, p less than 0.98). TAT levels did not correlate with AT-III levels (r = -0.36, p less than 0.49), but there was an inverse correlation between SF and AT-III (r = 0.60, p less than 0.001). If AT-III levels were above 0.30 U/ml, SF levels remained low, whereas SF levels were increased in patients with AT-III levels below 0.30 U/ml. These findings suggest that if sufficient AT-III is present, thrombin formation is adequately controlled, whereas at low levels of AT-III, thrombin escapes inactivation by AT-III and may act upon fibrinogen, leading to the formation of SF and a low-grade DIC. SF levels correlated well with D-dimer levels (r = 0.55, p less than 0.001), which is consistent with DIC and secondary fibrinolysis. IN CONCLUSION: (1) thrombin formation is increased in liver cirrhosis, as indicated by increased TAT levels in 21 of 51 patients; (2) the plasma concentration of AT-III appears to be of major importance for the development of DIC. The present study provides evidence for DIC in severe liver cirrhosis when AT-III levels are less than 0.30 U/ml. PMID- 1447500 TI - A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three year results. AB - The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolone group. Hepatic mortality was 3/19 (prednisolone), 5/17 (placebo) (p = n.s.). For all liver blood tests the trend favoured prednisolone treatment, though the differences were only significant for alkaline phosphatase and protein. All immunoglobulins fell significantly. Quantitative ELISA determination of antimitochondrial antibody showed a significant fall in the prednisolone group compared with placebo (p less than 0.001 at 1 year, p less than 0.05 at 3 years). Deterioration in histology (appearance of cirrhosis) was more common in the placebo group. Overall hepatic function (hepatic mortality, doubling in bilirubin, 6 milligrams fall in albumin, de novo appearance of cirrhosis or symptoms of portal hypertension) was significantly worse in the placebo group (p less than 0.01). After 3 years no significant differences could be detected in bone mineral content (single photon absorptiometry of radius and femur) between the two groups or in comparison with other PBC patients. Thus, after 3 years, prednisolone treatment was associated with a better overall hepatic outcome and little evidence of increased bone loss. PMID- 1447501 TI - Sodium fluoride prevents bone loss in primary biliary cirrhosis. AB - Low-bone-turnover osteoporosis is a common complication of primary biliary cirrhosis (PBC). Since sodium fluoride stimulates bone formation we assessed the effect of this drug on bone mass in a 2-year, prospective, double-blind trial including 22 women with PBC who were randomly assigned to receive sodium fluoride (50 mg/day) or placebo. All received calcium supplements and low doses of vitamin D. Bone mineral density of the lumbar spine was measured by dual-photon absorptiometry initially and every 6 months. Vertebral fractures were evaluated in thoracic and lumbar spine initially, and after 1 and 2 years. Seven patients in the fluoride group and eight in the placebo group completed the trial. In the fluoride group, bone mineral density did not change after 2 years (initial 1.05 +/- 0.07, final 1.07 +/- 0.06 g/cm2; p = n.s.). In the placebo group, however, bone mineral density decreased significantly (initial 1.00 +/- 0.07, final 0.93 +/- 0.06 g/cm2; p = 0.03). Moreover, in the fluoride group bone mineral density increased by 2.9 +/- 3.6%, and in the placebo group decreased by 6.6 +/- 2.6% (p = 0.04). None of the patients developed new vertebral or non-vertebral fractures. Treatment with sodium fluoride did not impair liver function or cholestasis in PBC. These results indicate that sodium fluoride prevents bone loss in PBC and therefore might be considered as a possible therapeutic agent for osteoporosis associated with this liver disease. Since a small number of patients completed the trial, further studies are required. PMID- 1447502 TI - Echo-Doppler evaluation of acute flow changes in portal hypertensive patients: flow velocity as a reliable parameter. AB - In order to evaluate the behavior of the portal vein cross-sectional area during changes in portal flow, two groups of subjects were analyzed in two blinded cross over studies using echo-Doppler flowmetry. The first group (I) consisted of 21 patients with cirrhosis and 16 controls. They received a standardized meal which is known to increase portal flow. The second group (II) consisted of 31 patients with cirrhosis who received a dose of propranolol which is known to decrease portal flow. In Group I, 30 min after the meal, the portal vein blood velocity increased by 35 +/- 6% (p less than 0.01) in cirrhotic patients and by 55 +/- 5% (p less than 0.01), in normal subjects. The portal vein cross-sectional area increased significantly in normal subjects (22 +/- 2%, p less than 0.01) but not in cirrhotic patients (4 +/- 2%, n.s.). In Group II, 2 h after propranolol, there was a significant decrease in portal blood velocity (-14 +/- 2%), whereas the portal vein cross-sectional area did not show any significant changes. These data demonstrate that, in portal hypersensitive patients, the portal area measured by echo-Doppler flowmetry can be assumed to be constant and hence its calculation to estimate changes in portal blood flow can be omitted. Therefore, the use of blood velocity alone is suggested to monitor acute changes in flow in portal hypertension using Doppler flowmetry. The elimination of the portal vein cross sectional area measurement simplifies the quantitative calculation of portal hemodynamics and increases the reliability of the technique by avoiding a source of error. PMID- 1447503 TI - Quantitative analysis of proliferating sinusoidal cells in dimethylnitrosamine induced cirrhosis. An immunohistochemical study. AB - Proliferating lipocytes (fat-storing cells or perisinusoidal stellate cells of the liver) were detected by in vivo incorporation of bromodeoxyuridine (BrdU) in an experimental model of cirrhosis in the rat by dimethylnitrosamine. Lipocytes were identified by sequential double immunohistochemical staining on frozen sections using anti-desmin antibodies as a marker of cytoplasmic intermediate filaments followed by anti-BrdU antibodies to identify S-phase nuclei in animals treated for 7, 14 or 21 days. The number of desmin-positive (lipocytes) and desmin-negative (Kupffer and endothelial cells) sinusoidal cells incorporating BrdU was recorded. The labelling index of lipocytes was calculated as the percentage of BrdU-labelled desmin-positive cells with respect to total number of lipocytes. In control animals, when the total number of lipocytes was 153.9 +/- 11/mm2 (mean +/- 1 S.E.) the number of desmin-positive S-phase sinusoidal cells never exceeded 6.8 +/- 1.2/mm2 with a maximum labelling index of 4.3 +/- 0.5%. At 7 days of treatment, the values were respectively 236 +/- 26.5/mm2, 53.2 +/- 5.9/mm2 and 22.6 +/- 0.5% (p less than 0.001 vs. controls), while, at 21 days they were 272.5 +/- 21.2/mm2, 23.3 +/- 4.0/mm2 and 8.5 +/- 1.1% respectively (p less than 0.01). These results show that hyperplasia of lipocytes represents an early reaction to dimethylnitrosamine-induced liver injury. The local accumulation of lipocytes appears to occur in areas where fibrous septa develop later on. PMID- 1447504 TI - Uridine diphosphoglucose restores lipocyte proliferation in the regenerating liver of ethanol-treated rats. AB - The effect of continuous intraperitoneal infusion of uridine diphosphoglucose on ethanol-induced suppression of lipocyte proliferation was studied in regenerating rat livers from 1-4 days after hepatectomy. Proliferating lipocytes were positively identified using a two-sequence immunohistochemical staining for cytoplasmic desmin and bromodeoxyuridine-labelled nuclei. Hepatectomy rapidly stimulated lipocyte proliferation which peaked 2 days after hepatectomy (labelling index, 17.9 +/- 0.81%). uridine diphosphoglucose or glucose infusion did not modify the time course of lipocyte proliferation. Ethanol feeding to hepatectomized rats receiving saline or glucose infusion resulted in a 71% (p less than 0.005) and 61% (p less than 0.005) inhibition of lipocyte proliferation, respectively, 2 days after hepatectomy, thereby abolishing the characteristic proliferative peak observed in rats not treated with ethanol. In contrast, uridine diphosphoglucose infusion doubled the labelling index (13.1 +/- 2.34%) in ethanol-fed rats compared to that in corresponding rats treated with saline (5.28 +/- 1.29%; p less than 0.005) or glucose (6.51 +/- 0.64%; p less than 0.005). This resulted in the appearance of a proliferative peak, albeit smaller than normal, 2 days after hepatectomy. In sham-operated rats, lipocyte proliferation was low with a labelling index of 1.88 +/- 0.13% at the time of operation and of 1.69 +/- 0.23% 2 days thereafter. Uridine diphosphoglucose infusion to sham-operated rats for 2 days did not significantly affect lipocyte proliferation (labelling index 1.79 +/- 0.06%). The present study demonstrated that uridine diphosphoglucose does not affect lipocyte proliferation in the regenerating or sham-operated livers, but that it partially reverses the ethanol induced suppression of lipocyte proliferation after hepatectomy. PMID- 1447505 TI - Interleukin-6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis. AB - The in vitro production of the acute-phase mediator interleukin-6 by peripheral blood monocytes derived from patients with various liver diseases was studied. Compared with healthy controls (n = 45; 860 +/- 92 U/ml, mean +/- SEM), monocytes from patients with chronic hepatitis B produced significantly lower amounts of interleukin-6 (n = 14; 424 +/- 126 U/ml) after stimulation with lipopolysaccharide (p = 0.02), whereas monocytes from patients with chronic hepatitis non-A, non-B secreted normal amounts of interleukin-6 (n = 13; 672 +/- 151 U/ml; n.s.). In contrast, monocytes of patients suffering from alcoholic liver cirrhosis (n = 22; 1310 +/- 153 U/ml) or primary biliary cirrhosis (n = 6; 1450 +/- 186 U/ml) produced higher amounts of interleukin-6 than healthy control individuals (p = 0.03, respectively). Lipopolysaccharide-stimulated monocytes derived from patients with acute hepatitis A, B and non-A, non-B showed an interleukin-6 production not different from that seen in healthy control individuals and did not experience a discernible change during the course of the acute disease. These results suggest that the production of the acute-phase mediator interleukin-6 varies in chronic liver disease in accordance with various etiologies with a reduced lipopolysaccharide-inducible interleukin-6 response in chronic hepatitis B and an enhanced response in alcoholic liver cirrhosis and primary biliary cirrhosis. PMID- 1447506 TI - Evidence for the production of high amounts of interleukin-6 in the peritoneal cavity of patients with ascites. AB - The ascites and serum concentrations of interleukin-6 (IL-6) and interleukin-1 (IL-1) were determined in 21 patients with hepatic ascites and in 9 patients with malignancy-associated ascites. There was no evidence for bacterial peritonitis in any patients. All ascites samples contained high amounts of immunoreactive IL-6 [hepatic ascites 1730 +/- 2130 pg/ml (mean +/- SD), 1160 pg/ml (median); malignant ascites 4020 +/- 1510 pg/ml (mean), 3820 pg/ml (median)] but no IL-1. The mean ascites to serum ratios of IL-6 were 96 (median 49) in patients with hepatic ascites and 587 (median 480) in patients with malignant ascites. Ascites IL-6 was biologically active as determined by the B9 cell bioassay. The results indicate that even in the absence of infection IL-6 is produced in high amounts in the peritoneal cavity of patients with hepatic or malignant ascites. PMID- 1447507 TI - Primary cultures of human hepatocytes: a unique system for studies in toxicology, virology, parasitology and liver pathophysiology in man. PMID- 1447508 TI - Ascites as the first manifestation of Brucella granulomatous hepatitis. PMID- 1447509 TI - Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. PMID- 1447510 TI - Prevalence of hepatitis B virus in Kurdish refugees. PMID- 1447511 TI - Frequent sporadic hepatitis E in west Africa evidenced by characterization of a virus-associated antigen in the stool. PMID- 1447512 TI - Paul Pirlot (1920-1990). PMID- 1447513 TI - Some observations on the fine structure of the sensory cells in the neuromasts (ordinary lateral line) of the teleost Gambusia affinis. AB - The structural and ultrastructural features of the sensory cells in the neuromasts of G. affinis were studied. These pear-shaped cels present a tuft of sensory hairs rising from the apex and a highly dense cytoplasm with multivesicular bodies, dyctiosomes, granular and smooth endoplasmic reticulum and numerous mitochondria. Large round granular dense bodies of an unknown nature can be observed inside and outside the nucleus. A great number of vesicles are present at the base of the cells, some of them associated with an afferent synapse, which also presents a presynaptic dense body. An efferent synapse with a nerve ending full of vesicles and a postsynaptic subsurface cisterna is also present at the base of these cells. PMID- 1447514 TI - Ultrastructural localization of insulin-like immunoreactivity in the rat spinal cord. AB - Insulin-like immunoreactive neurons were localized in the cervical, thoracic, lumbar and sacral segments of the rat spinal cord. Neurons from both the ventral and dorsal horns were labelled. The insulin-like reaction product was predominantly localized in the cell nucleus and the proximal and distal dendrites. In the labelled cell nucleus, the reaction product was scattered throughout the nucleoplasm and the inner and outer nuclear membranes but not within the nucleolus. In the labelled dendrites, the reaction product was closely associated with the parallel arrays of neurotubules. Most of the labelled distal dendrites were postsynaptic to non-labelled axon terminals. A labelled dendrite often formed the central element of a synaptic glomerulus with several non labelled axon terminals. It is hypothesized that the insulin-like substance(s) may be modulating nuclear activities as well as neurotransmission at the synapse in the spinal cord. PMID- 1447515 TI - Degenerative and regenerative phenomena in brain heterotopic homoplastic transplants of adult Triturus carnifex (Urodele Amphibians). AB - The brains of adult Urodele Amphibians (Triturus carnifex Laur.) were homoplastically transplanted in conditions of complete morpho-functional isolation. Despite the heterogeneous nature of the histological aspects observed, the results point to the following general pattern for the fate of the brain transplants: 1) rooting phase (about day 5 after the operation) as indicated by degenerative patterns affecting the various encephalic districts and mainly involving the more peripheral neurons and the nerve fibers, and to a lesser extent the periventricular gray and the ependyma; 2) phase of rejection by host (from day 10 until end of experiment on day 30) as indicated by lymphocytic infiltration, the presence of macrophages and pyknoses, and the formation of a connective tissue capsule surrounding the transplant; 3) regenerative phase (from about day 10) as indicated by the onset of mitotic activity affecting elements of the ependymal epithelium and the periventricular gray, particularly in the telencephalic district. By the end of the experiment, in most of the transplants examined, degenerative processes were found to have prevailed over the regenerative phenomena. However, in some cases, and particularly in one of them, a distinctly higher degree of structural organization of neurons and nerve fibers can be observed at the telencephalic level. It may be postulated that, whenever a greater degree of compatibility exists between the host and the transplanted organ, it is possible, even in conditions of complete morpho-functional isolation, for the brain to express regenerative power through the ependyma and the matrix zones which have already been identified by some Authors in telencephalic periventricular areas or scattered through the mesencephalic gray matter. PMID- 1447517 TI - The fine structure of the inferior colliculus in the cat. II. Synaptic organization. AB - The synaptic organization of the central nucleus of the inferior colliculus (ICc) of the cat has been investigated by means of electron microscopy. On the basis of the following criteria: the size and the shape of the synaptic vesicles, the distribution and density of the vesicular population, the size and the shape of the synaptic boutons, their origin, and the characteristics of the active synaptic zones, several types of synaptic boutons in the ICc have been discriminated: LR1, LR2, SR, SSB, F1, F2, P, DCV-terminals, and "d"-profiles. The LR1, LR2, SR and SSB bouton types contain clear, round or slightly oval synaptic vesicles and form asymmetrical synapses mainly with middle sized and small dendrites and dendritic spines. LR2-terminals not rarely contact also the neuronal perikarya, whilst the SR-boutons form exclusively axodendritic and axospinous synapses. The P, F1 and F2-boutons contain a pleomorphic vesicular population (P-boutons), with an increased degree of vesicle flattening (F1 and F2 boutons) and form symmetrical axosomatic, axodendritic and axospinous contacts. Especially often the F1-boutons form axosomatic synapses, whilst the F2-terminals end mainly on dendrites. The DCV-boutons contain a mixed population of clear round synaptic vesicles and large dense core vesicles. The DCV-boutons terminate mainly on spines and small distal dendrites by means of asymmetrical synaptic specializations. The "d"-profiles originate from dendrites, and are identical to the thalamic "d"-profiles but are far more rarely observed in the ICc. The "d" profiles are postsynaptic mainly to the LR-types, and are presynaptic to conventional dendrites, thus participating in synaptic triads. The axonal hillocks and the initial axonal segments of the larger perikarya in the ICc are substantially innervated mainly by LR and P-boutons. Glomerulus-like formations are fairly often, especially around the LR1-terminals, contacting several small postsynaptic targets. True synaptic glomeruli are only rarely observed. Branching myelinated axons are found mainly within the fibrodendritic laminae, whilst unmyelinated collaterals, emitted by myelinated axons are especially often encountered outside the laminae. Various types of myelinated axons form nodal synapses. PMID- 1447516 TI - [Neurohistological findings in the parietal cortex of children with chromosome aberrations]. AB - In Golgi-Cox impregnated parietal cortex (regio postcentralis) of two children (20 months of age or 6 years of age) with Down's syndrome the pyramidal neurons of lamina III and V were investigated qualitatively and quantitatively. Fives types of pyramidal neurons were classified and compared statistically. As parameters for characterizing pyramidal neurons served dendritic lengths for all dendritic orders, within single dendritic fields, in apical and basal parts of the dendritic tree, and of the whole neuron. Normal values obtained in brains of the same age were not available, therefore, we compared our results with those published by other authors. To study the developmental stage of the pyramidal neurons in both our cases, we compared analogue pyramid types in both brains. The pyramidal neurons showed different qualitative abnormalities in their dendritic tree configuration. The comparison of quantitative parameters suggests the pyramidal cells of the older child show more degenerative changes, concerning especially lamina III pyramids but in lamina V pyramids as well. These changes might be structural correlates of the mental retardation: the 6 year old child was strongly retarded in clinical symptoms, too. The results are discussed and critically evaluated in view of the clinical signs of Morbus Down. Finally we should await the investigations of more cases for demonstrating the normal as well as the abnormal development of the human cerebral cortex. PMID- 1447518 TI - Developmental stages of the vomeronasal organ in the rat: a light and electron microscopic study. AB - This paper describes the development of the rat vomeronasal organ from the stage of anlage until adulthood. Groups of four rats were sacrificed daily from prenatal day 13 (E13) until birth; at days 2, 4, 7, 10, 14 and 16 after birth; weekly from day P21 to P42 plus an additional group of adults. The vomeronasal organs were processed for light microscopy, including alcian blue-PAS and NADH diaphorase reactions, and also for electron microscopy. For summarizing our results we propose the following developmental stages: 1. Anlage (E13). 2. Early morphogenesis (E14-16). 3. Late morphogenesis (E17 to birth). 4. Initiation of secretory activity (First postnatal week). 5. Cytoarchitectural maturity (2nd postnatal week). 6. Complete maturity (From 3rd postnatal week onwards). Our results on the maturation of the histological structure and the histochemical reactions, indicate that there may be some functional activity at birth but the development of the organ still continues during the first three postnatal weeks to acquire its full functional capability. PMID- 1447519 TI - Systematisation of the olfactory bulb efferent projections in a lemurian primate: Microcebus murinus. AB - In order to investigate a sensorial pathway essential in animal behavior, the efferent projections of the olfactory bulbs in Microcebus murinus were identified after transection of one olfactory peduncle and revelation of degenerating fibers by various silver staining methods. Total and partial sections have enabled the demonstration of the involvement in the olfactory projection areas of each olfactory tract: the lateral olfactory tract (LOT) and the intermediate olfactory tract (IOT), either via the medial forebrain bundle (MFB) or not. The IOT fibers innervate the cortex, the anterior olfactory nucleus, the caudate-putamen, the septum and the hippocampus on both sides. The LOT fibers reach the olfactory tubercle, the piriform cortex, the entorhinal cortex and the amygdala on both sides. Olfactory fibers could also be observed in the MFB innervating on both sides firstly the hypothalamic areas (the lateral hypothalamus, the suprachiasmatic, posterior supraoptic, mammillary nuclei and the median eminence), and then the mesencephalic structures (the locus coeruleus and the raphe nuclei). It may be concluded that the olfactory bulbs are not only connected with above-mentioned telencephalic areas, but are also directly related to the vegetative and integrative brain areas located in the hypothalamus and the brainstem and especially with the major nuclei which play an essential role in neurovegetative, neuroendocrine and behavioral regulation. PMID- 1447520 TI - Primary projections of the lateral line nerves in larval sea lamprey, Petromyzon marinus L. An HRP study. AB - The primary central projections of the anterior and posterior lateral line nerves were determined in the larval sea lamprey, Petromyzon marinus L. using silver staining methods and axonal transport of horseradish peroxidase (HRP). Lateral line fibers course in the dorsal portion of the octavolateral area. At the level of their entry in the medulla, all the lateral line fibers originate ascending and descending branches. The anterior lateral line nerve consists of three roots: dorsal, intermediate and ventral. Afferents of the dorsal root project to the ipsilateral dorsal nucleus. The intermediate and ventral roots project ipsilaterally to the lateral neuropil of the medial nucleus and to the cerebellar lamina, but they do not cross the midline. Contralateral projections of this nerve were not found in larvae. Primary afferents of the posterior lateral line nerve project ipsi- and contralaterally to the medial neuropil of the medial nucleus. Ascending fibers course in the ipsilateral medial nucleus, enter the cerebellar lamina, cross the midline and descend to the lateral neuropil of the contralateral medial nucleus. In the cerebellar lamina, the fibers of the anterior lateral nerve are located ventrolaterally to those of the posterior lateral nerve. Lateral line efferents were not observed in larvae. PMID- 1447521 TI - Immunocytochemical localization of GnRH in the hypothalamus of the bat Miniopterus schreibersii schreibersii. AB - The distribution of gonadotropin-releasing hormone (GnRH) has been examined in the hypothalamus of adult female bats, Miniopterus schreibersii schreibersii, along annual reproductive cycle by means of light-microscopic immunocytochemistry. GnRH-immunoreactive cells are localized throughout the medial basal hypothalamus, being specially numerous in the arcuate nucleus. They are generally bipolar or monopolar neurons with smooth contour, although spiny cells were also found exclusively in the arcuate nucleus from periovulatory bats. Depletion in both number and immunocytochemical labelling of GnRH perikarya is detected in pregnant and lactating bats. GnRH-immunoreactive fibers are distributed in the internal layer of the median eminence and the infundibular stalk. Pregnant and lactating animals show lower GnRH fibers content and a less intense labelling than in periovulatory and hibernating conditions. The results suggest that changes in the secretory activity of GnRH neurons may be associated with hibernation and delayed implantation that suffer these mammalian species. PMID- 1447522 TI - Golgi study on neurons and fibers in Nucl. rotundus of the thalamus in chicks. AB - The structural arrangement of nucleus rotundus was studied by Golgi method. Large, multiangular principal neurons, their dendrites and dendritic terminals were observed. The long dendrites and their side-branches course parallel and/or perpendicular to each-other and they are arranged about in dorso-ventral latero medial and rostro-caudal directions. The dendrites and their side-branches develop characteristic terminal branchings. These dendritic terminals overlap each-other and the area is called dendritic terminal field. The tecto-rotundal fibers traverse the nucleus in large bundles and the final sections of fibers join to the dendrites of principal neuron and terminate in dendritic terminal fields. PMID- 1447523 TI - [A study of risk factor in osteoporosis, femoral neck fracture and colles' fracture]. AB - This work studied risk factors of osteoporosis, femoral neck fracture and Colles' fracture. The results were compared with those of a healthy group. Milk intake was frequent in the healthy group, but rare in the femoral neck fracture or Colles' fracture group. Most of osteoporosis and femoral neck fracture group were bed ridden, or stayed indoors for a long time before injury. They weighed less and were thin as compared to the healthy group. Decrease of activities of daily living and less body weight were risk factors of osteoporosis and femoral neck fracture, but these risk factors were more predominant in the femoral neck fracture than osteoporosis group. In this study, 74.4% of the patients with femoral neck fracture also had osteoporosis and 33.3% with Colles' fracture had osteoporosis. Colles' fracture was related to injury force and femoral neck fracture was found to be closely related to osteoporosis. PMID- 1447525 TI - [A new intramedullary nailing system for long bone fractures--biomechanical evaluation and animal study of a new intramedullary nail]. AB - Interlocking intramedullary nails have expanded their application to the fixation of long bones especially for unstable or comminuted fractures. However, there are certain drawbacks in this method: prolongation of operative time and increased radiation hazard to the patient as well as to the surgical staff, the latter of which is especially a problem in the distal interlocking under fluoroscopic control. In order to solve the problem a new intramedullary nail (J-type) was developed and tested in vitro with Hiprox femur models as well as in vivo using canine models. The nail made of Ti-6Al-4V alloy is composed of an inner nail and an outer cylinder. The proximal portion is transversely fixed with two screws, while the distal portion is fixed into the cancellous bone with four expandable blades. The strength of fixation with this nail was compared to those with four other commercially available interlocking nails as to bending, tortional and compression stiffness as well as to the durability against repeated compression. In the present in vitro and in vivo experiments, a newly developed intramedullary nail (J-type) provides evidence for satisfactory mechanical strength. The use of J-type nail also contributes to shorter operative time and reduction of radiation hazard. PMID- 1447524 TI - [Immunohistochemical study on the effect of high tibial osteotomy on the distribution pattern of neuropeptides in the synovium of the osteoarthritic knee]. AB - Synovial tissue was obtained from 18 knees with medial compartmental osteoarthritis (OA) and from 20 knees on which a high tibial osteotomy had been performed. Neuropeptides were stained with a specific avidin-biotin-peroxidase method. Comparisons were made of the incidence of staining as well as the location of staining within the synovia (medial, lateral, and suprapatellar regions). The results showed that the synovium had an extensive neural network of both the somatic and autonomic nervous systems. In the medial synovium of the preoperative knees, the neuropeptides were found in abundance. An especially strong response for substance P (SP) and calcitonin gene-related peptide (CGRP) was observed at the free nerve endings. However, the postoperative incidence of SP-positive free nerve endings was reduced to 54% of the preoperative amount and the inflammation subsided in the medial region. These findings suggested that free nerve endings containing SP might be mainly involved in the inflammation and pain of OA. PMID- 1447526 TI - [An experimental study on repair and recovery of lacerated muscles--histological and histochemical observations]. AB - A histological and histochemical study of the repairing process of skeletal muscle after transection and immediate suture was conducted using the gastrocnemius muscle of hamsters. The muscles were examined from one hour to twelve weeks after operation and were prepared as specimens for either transverse or longitudinal sections. During the first two days, necrotic fibers were scavenged by macrophages. Early regenerating fibers appeared at the extent of about 1-2 mm on both sides of the cut ends by the fourth day. After one week, myotubes identified as type 2C were abundant. By the fourth week regenerating fibers had grown longitudinally and bridged the injury site between the proximal and distal muscle fiber segments. After six weeks, they had almost matured histochemically. After eight weeks, there was substantial repair of the injury site with scarce fibrous tissue. This study has clearly demonstrated the histological and histochemical findings of repairing process of the skeletal muscle after transection. PMID- 1447527 TI - Preservation of bone morphogenetic protein in heat-treated bone. AB - In operations of bone tumors, reimplantation of resected bone after boiling or autoclaving is a simple means of obtaining both tumor necrosis and skeletal reconstruction. However, such reimplants lose their osteogenesity. We investigated whether bone inductive ability could be maintained in heat-treated bone. Bone morphogenetic protein (BMP) extracted from rabbit bone after heating for various periods at different temperatures was implanted into the muscles of mice to evaluate osteogenetic activity. The maximum new bone formation was observed in specimens treated at 70 degrees C for 10 minutes, followed by those treated at 70 degrees C for 15 minutes. We then measured the temperature in the center of a cortical bone heated in 0.15 N NaCl solution at 50 degrees, 60 degrees, 70 degrees, 80 degrees, and 90 degrees C. Cortical bone center temperature reached that of the surrounding solution within 2.5 minutes. These results indicated that heating at 70 degrees for 10 to 15 minutes was suitable for heat treated-bone to maintain bone inductive ability. PMID- 1447528 TI - [Neurological disorders in orthopaedic practice]. PMID- 1447529 TI - [Treatment of injured extensor tendons in the hand]. PMID- 1447530 TI - [Fatigue properties of restorative dental materials]. PMID- 1447531 TI - [Evaluation of school dental health activities in Hiraizumi primary school, Iwate prefecture]. AB - The purpose of this study was to evaluate the health activities in Hiraizumi primary school, Iwate prefecture. As a result of intensive dental health activities from 1978 to 1990, which consisted of tooth brushing instruction by class, dental education for the schoolchildren and their guardians, utilization of fluoride mouth rinsing (once a week), and, by following a model school of caries prevention designated by the Ministry of Education et al., the oral health status of the Hiraizumi primary schoolchildren improved significantly compared with those of the Ohya primary schoolchildren who followed the routine school dental health activities. The results of questionnaires, taken from both primary schoolchildren in 1986 and 1989, show that the oral health behavior of the Hiraizumi primary schoolchildren also improved. PMID- 1447532 TI - [Clinical study of maxillofacial fractures sustained during sports and games]. AB - We performed a clinico-statistical study of the maxillofacial fracture due to sports during the period of 15 years between 1977 and 1991. Eighty-nine patients were seen with injuries resulting from 21 different sports. The incidence of the fracture was most common in rugby, followed by ski, baseball and soccer. Males were shown to be more prone to maxillofacial fracture than females (5.4:1) and the highest incidence of injuries involved the 20-29 age group followed by the 10 19 age group. The major parts of the fracture were the mandible and the alveolar process. Conservative therapy such as maxillomandibular fixation was usually performed and the clinical course was good. It was suggested that the prevention of the sports-related fracture and the time of returning to sports after the fracture will require further study. PMID- 1447533 TI - [Studies on caries of Ishibashi rat--III. Experimental caries in Ishibashi rat]. AB - Dental caries was experimentally induced in the Ishibashi rats (ISR) by feeding them with conventional diets or with caries-producing diets, and the pattern and severity of their induced carious lesions were compared with those of the Sprague Dawley rats (SD). Simultaneously, serum antibody titers against Streptococcus mutans and calcium and phosphorus concentration in the sera and in the femurs were compared between the ISR and SD. The results were as follows: 1. When judged by cavities, ISR showed a higher carious incidence and average number of cavities per one rat than the SD, whichever diet the rats were fed. 2. When judged by fissure caries observed on the thin sections of the teeth, both the carious incidence and average number of fissure lesions in the ISR were not always high compared with those in the SD, and there seemed to be a great variation of caries susceptibility in the ISR. 3. Caries in the ISR seemed to be more progressive than that in the SD. 4. There were no differences in the serum antibody titers against the S. mutans between the ISR and SD. 5. No differences in the concentration of calcium and phosphorus in the sera and femurs were observed between the ISR and SD, whichever diet they were fed. PMID- 1447534 TI - [Alveolar bone resorption process in molar tooth region in calcium-deficient rats]. AB - The present study was carried out to investigate the alveolar bone resorption in the molar tooth region in the rats fed a low calcium diet. Male Wistar rats (70 85g in body weight) were either fed a low calcium diet (0.05% Ca, 0.35% P) or a control diet (0.5% Ca, 0.35% P) by using a pair feeding technique. The rats were sacrificed at intervals of 3, 6, 9 and 20 days during the experimental period. Contact microradiograph of the second molar region of the mandible showed that the cancellus bone as well as the endosteal surface of the cortical bone were progressively resorbed soon after the start of low calcium feeding. At day 9, the amount of bone was reduced to about half of the control rats and 80% of the bone was diminished at day 20. In spite of the severe bone resorption, the alveolar bone proper that surrounds the molar sockets and a few cancellus bone were seen remaining and the occlusal function of the molar tooth seemed to be maintained. These results suggest that the alveolar bone quickly responded to the low calcium diet resulting in bone resorption and that the bone in the supporting tissues of the molar tooth seems to be not affected by the calcium deficiency. PMID- 1447535 TI - Anesthesia support systems. PMID- 1447536 TI - Real-time respiratory monitoring workstation--software and hardware engineering aspects. AB - We have applied advanced real-time techniques in software, that are intensively used in critical areas like space research and defence applications, to realise an Integrated Real-Time Respiratory Monitoring System at the Thorax Anesthesiology, Academic Hospital Rotterdam. The system is called the 'SERVO WINDOW'--a window to the servo ventilator. The heart of the system is a real-time kernel that uses preemptive scheduling to achieve multitasking on a IBM PC compatible hardware platform. To the clinician this means that he gets all relevant information from one source i.e. the Respiratory Workstation. The waveforms of the airway pressure, airway flow and the expired CO2 curve are displayed continuously on the screen. The Vector Loops like Pressure Volume, Flow Pressure and Flow Volume loops are also available in addition to the lung mechanics parameters like Expiratory and Inspiratory Resistances, Compliances, Peak Pressure, PEEP, etc. The Single Breath Diagram i.e. expired CO2 concentration versus volume and dead space ventilation is also calculated. The blood gas analysis data is plotted in convenient diagrams like the O2-CO2 diagram, Oxygen Chart, etc. The trend of all these parameters are available with a granularity of one minute. An industry standard laser printer is used for report generation to produce reports of the real-time waveforms, parameter values and the trends. User interface is through easy menus with the traditional keyboard, touchscreen including keyboard on screen for data entry and the mouse. PMID- 1447537 TI - AxAudit--anaesthetic audit system. AB - A bar code based computerised anaesthetic audit system is described. The system consists of a data entry and validation module resident on a remote hand-held computer and a central database module resident on a desktop computer, capable of conducting extensive searches, analysis, graphing and reporting of captured data. Information is entered into the computer by 'swiping' a bar code reader across required bar codes. Information entered is constantly validated and the computer ensures a minimum data set is captured for every patient. Since data is transferred directly into a computer at the point of clinical activity, a large data set can be presented to the clinician, ensuring as complete a patient record as possible and avoiding the problems associated with traditional form-filling and the subsequent transfer of information onto a computer. The hand-held computer has data cards which can hold information on approximately 200 patients. These cards can be inserted directly into a card reader attached to a desktop computer, thus automating the process of data transfer. The AxSys Anaesthetic Audit system, AxAudit, is a bar code based, computerised audit system developed with the aim of executing effective audit in the course of normal clinical activity. PMID- 1447538 TI - Computer assisted management of information in an intensive care unit. AB - In order to use the capability of computers for handling large amounts of information, we developed a program for the acquisition, handling, storage and retrieval of administrative and clinical information generated in the 20 bedded multidisciplinary critical care unit of a University Hospital. At an initial phase a personal computer (PC) was used to collect information from 4362 patients, that included registration data, coded admission problems, techniques and special treatments, and final diagnosis. This information combined with free text provided a discharge report. Complementary programs allowed calculation and storage of hemodynamic and gas exchange parameters. This experience led to a second phase in which a computer with microprocessor Intel 80386 at 25 MHz, 8 MB RAM, 310 MB hard disk and a streamer for 150 MB cartridge tape back up, using UNIX operating system, permitted multiple users working simultaneously through 1 central console and 7 ASCII terminals. Data input included demographic data, previous and admission problems in coded form, present history and physical examination in free text, list of present problems in coded form, comments on evolution, record of special techniques and treatments, laboratory data, treatment, final diagnosis and facility for using all the information to elaborate the final report. Side modules provide help for drugs dosing, protocols for specific conditions and clerical routines. The system is open for connection to other areas of the Hospital. Data from more than 2000 patients have been included so far.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447539 TI - A decision table and rule based interpretation system for epileptic discharges. AB - The representation of the various features of waveforms and their correlations, in EEG recording for the diagnosis of different diseases have been carried out by many researchers due to the impact of knowledge based on expert systems development tools and techniques. The realisation of these system requires a specific hardware and software tool for its implementation, which may be a costly affair. The design and development of low cost effective system for the diagnosis of epileptic patients have been reported in this paper. Two different and linked (at certain stage) approaches (i) decision table; (ii) rule based system have been followed to model the reasoning processes of physician in the diagnosis. In the decision table the features of specific waveforms of EEG are represented in the tabular form. The features are obtained from a 8086 microprocessor based data acquisition system. The rule based system is designed with IF and THEN form of rules using Turbo-Prolog as programming language tool and is implemented on low cost PC-AT. The results obtained are at an intermediate stage of data processing by decision tables and at the final stage being carried out by rule based model. The performance of the system is evaluated by recording of EEG of some epileptic patients. The results obtained are comparable and to a certain extend appreciable in the opinion of the physician. PMID- 1447540 TI - A portable target controlled propofol infusion system. AB - A portable target controlled infusion system for propofol has been developed based on a Psion hand-held microcomputer and the Ohmeda 9000 syringe pump. The system uses a pharmacokinetic model which describes the distribution and elimination of propofol to achieve and maintain any selected target blood concentration. Target blood concentrations of 1 micrograms/ml, 3 micrograms/ml and 5 micrograms/ml were selected in laboratory trials and the cumulative volumes delivered by the Psion system each minute were compared with the theoretical output calculated by the pharmacokinetic model. The results obtained showed that the computer system delivered volumes which were always within 2% of the theoretical values. This system offers a convenient and simple method of maintaining anaesthesia using propofol. PMID- 1447541 TI - The influence of "preparedness" on autoshaping, schedule performance, and choice. AB - Two groups of experimentally naive pigeons were exposed to an autoshaping procedure in which the response key was mounted on the wall (the conventional location) or on the floor of the chamber. In two experiments, subjects readily responded to the wall key, but floor-key subjects required shaping. A subsequent experiment compared performance of wall- and floor-key groups on an ascending series of fixed-ratio schedule values, resistance to extinction, differential reinforcement of other behavior, and reversal of key assignment. Each experiment was followed by several sessions of fixed-ratio training; the performance of the wall- and floor-key groups was almost identical throughout. In the final experiment, a fixed-ratio requirement could be completed on either or both keys. Birds initially chose the key on which they had responded during the preceding (reversal of key assignment) experiment. However, within a few sessions both groups showed almost exclusive preference for the floor key. Preference for a key located on the floor may follow from the fact that pigeons are ground feeders and may thus be more "prepared" to peck the floor than to peck a wall. However, autoshaping, under the conditions prevailing here, occurred much more readily to the wall key, suggesting that pecking a vertical surface is more highly prepared. Difficulties in determining relative preparedness seem moot, however, given the lack of between-group differences in the intervening experiments. It is thus unlikely that schedule performances critically depend upon the specific operant response involved. PMID- 1447542 TI - Selective sensitivity of schedule-induced activity to an operant suppression contingency. AB - The sensitivity of pigeons' schedule-induced activity to operant consequences was studied in two experiments. During a 30-s interval between food presentations, a keylight stimulus brightened incrementally. Stable terminal key pecking and interim locomotor activity developed. An operant "setback" contingency was applied to activity. The contingency arranged for locomotor movements (detected by a nine-panel floorboard) to be followed by a resetting of the keylight brightness to a dimmer value and a 1-s delay of reinforcement (for individual responses). Experiment 1 showed that activity patterns were highly sensitive to their operant consequences. Accompanying key-peck rates were only transiently affected. In Experiment 2, the setback contingency was imposed during restricted portions of the trial, and differential operant control of activity was demonstrated. However, birds in this study produced higher rates of key pecking as activity rates were reduced. These results suggest that although schedule induced activity arises in response to the temporal arrangement of stimulus events, this behavior may retain considerable sensitivity to response-consequence relations. PMID- 1447544 TI - Intertrial-interval effects on sensitivity (A') and response bias (B") in a temporal discrimination by rats. AB - Killeen and Fetterman's (1988) behavioral theory of animal timing predicts that decreases in the rate of reinforcement should produce decreases in the sensitivity (A') of temporal discriminations and a decrease in miss and correct rejection rates (decrease in bias toward "long" responses). Eight rats were trained on a 10- versus 0.1-s temporal discrimination with an intertrial interval of 5 s and were subsequently tested on probe days on the same discrimination with intertrial intervals of 1, 2.5, 5, 10, or 20 s. The rate of reinforcement declined for all animals as intertrial interval increased. Although sensitivity (A') decreased with increasing intertrial interval, all rats showed an increase in bias to make long responses. PMID- 1447543 TI - Choice with delayed and probabilistic reinforcers: effects of variability, time between trials, and conditioned reinforcers. AB - In a discrete-trials procedure with pigeons, a response on a green key led to a 4 s delay (during which green houselights were lit) and then a reinforcer might or might not be delivered. A response on a red key led to a delay of adjustable duration (during which red houselights were lit) and then a certain reinforcer. The delay was adjusted so as to estimate an indifference point--a duration for which the two alternatives were equally preferred. Once the green key was chosen, a subject had to continue to respond on the green key until a reinforcer was delivered. Each response on the green key, plus the 4-s delay that followed every response, was called one "link" of the green-key schedule. Subjects showed much greater preference for the green key when the number of links before reinforcement was variable (averaging four) than when it was fixed (always exactly four). These findings are consistent with the view that probabilistic reinforcers are analogous to reinforcers delivered after variable delays. When successive links were separated by 4-s or 8-s "interlink intervals" with white houselights, preference for the probabilistic alternative decreased somewhat for 2 subjects but was unaffected for the other 2 subjects. When the interlink intervals had the same green houselights that were present during the 4-s delays, preference for the green key decreased substantially for all subjects. These results provided mixed support for the view that preference for a probabilistic reinforcer is inversely related to the duration of conditioned reinforcers that precede the delivery of food. PMID- 1447545 TI - Effects of response requirement and alcohol on human aggressive responding. AB - Nine men participated in two experiments to determine the effects of increased response requirement and alcohol administration on free-operant aggressive responding. Two response buttons (A and B) were available. Pressing Button A was maintained by a fixed-ratio 100 schedule of point presentation. Subjects were instructed that completion of each fixed-ratio 10 on Button B resulted in the subtraction of a point from a fictitious second subject. Button B presses were defined as aggressive because they ostensibly resulted in the presentation of an aversive stimulus to another person. Aggressive responses were engendered by a random-time schedule of point loss and were maintained by initiation of intervals free of point loss. Instructions attributed these point losses to Button B presses of the fictitious other subject. In Experiment 1, increasing the ratio requirement on Button B decreased the number of ratios completed in 4 of 5 subjects. In Experiment 2, the effects of placebo and three alcohol doses (0.125, 0.25, and 0.375 g/kg) were determined when Button B presses were maintained at ratio values of 20, 40 and 80. Three subjects who reduced aggressive responding with increasing fixed-ratio values reduced aggressive responding further at higher alcohol doses. One subject who did not reduce aggressive responding with increasing fixed-ratio values increased aggressive responding at the highest alcohol dose. The results of this study support suggestions that alcohol alters aggressive behavior by reducing the control of competing contingencies. PMID- 1447546 TI - Spreading activation versus compound cue accounts of priming: mediated priming revisited. AB - Spreading activation theories and compound cue theories have both been proposed as accounts of priming phenomena. According to spreading activation theories, the amount of activation that spreads between a prime and a target should be a function of the number of mediating links between the prime and target in a semantic network and the strengths of those links. The amount of activation should determine the amount of facilitation given by a prime to a target in lexical decision. To predict the amount of facilitation, it is necessary to measure the associative links between prime and target in memory. Free association production probability has been the variable chosen in previous research for this measurement. However, in 3 experiments, the authors show priming effects that free-association production probabilities cannot easily predict. Instead, they argue that amount of priming depends on the familiarity of the prime and target as a compound, where the compound is formed by the simultaneous presence of the prime and target in short-term memory as a test item. PMID- 1447547 TI - How semantic is automatic semantic priming? AB - Priming for semantically related concepts was investigated using a lexical decision task designed to reveal automatic semantic priming. Two experiments provided further evidence that priming in a single presentation lexical decision task (McNamara & Altarriba, 1988) derives from automatic processes. Mediated priming, but no inhibition or backward priming was found in this type of lexical decision task. Experiments 3 and 4 demonstrated that automatic priming was found only for associated word pairs, as determined by word association norms, and not for word pairs that are semantically related but not associated. It is argued that automatic priming in the lexical decision task occurs at a lexical level not at a semantic level. PMID- 1447548 TI - Form-based priming in spoken word recognition: the roles of competition and bias. AB - Phonological priming of spoken words refers to improved recognition of targets preceded by primes that share at least one of their constituent phonemes (e.g., BULL-BEER). Phonetic priming refers to reduced recognition of targets preceded by primes that share no phonemes with targets but are phonetically similar to targets (e.g., BULL-VEER). Five experiments were conducted to investigate the role of bias in phonological priming. Performance was compared across conditions of phonological and phonetic priming under a variety of procedural manipulations. Ss in phonological priming conditions systematically modified their responses on unrelated priming trials in perceptual identification, and they were slower and more errorful on unrelated trials in lexical decision than were Ss in phonetic priming conditions. Phonetic and phonological priming effects display different time courses and also different interactions with changes in proportion of related priming trials. Phonological priming involves bias; phonetic priming appears to reflect basic properties of activation and competition in spoken word recognition. PMID- 1447549 TI - Prelexical facilitation and lexical interference in auditory word recognition. AB - Phonological priming effects were examined in an auditory single-word shadowing task. In 6 experiments, target items were preceded by auditorily or visually presented, phonologically similar, word or nonword primes. Results revealed facilitation in response time when a target was preceded by a word or nonword prime having the same initial phoneme when the prime was auditorily presented but not when it was visually presented. Second, modality-independent interference was observed when the phonological overlap between the prime and target increased from 1 to 3 phonemes for word primes but not for nonword primes. Taken together, these studies suggest that phonological information facilitates word recognition as a result of excitation at a prelexical level and increases response time as a result of competition at a lexical level. These processes are best characterized by connectionist models of word recognition. PMID- 1447550 TI - Direct comparison of two implicit memory tests: word fragment and word stem completion. AB - In 3 experiments, the implicit memory tests of word fragment and word stem completion showed comparable effects over several variables: Study of words produced more priming than did study of pictures, no levels-of-processing effect occurred for words, more priming was obtained from pictures when Ss imaged the pictures' names than when they rated them for pleasantness, and forgetting rates were generally similar for the tests. A different pattern of results for the first 3 variables occurred under explicit test conditions with the same word fragments or word stems as cues. We conclude that the 2 implicit tests are measuring a similar form of perceptual memory. Furthermore, we argue that both tests are truly implicit because they meet Schacter, Bowers, & Booker's (1989) retrieval intentionality criterion: Levels of processing of words have a powerful effect on explicit versions of the tests but no effect on implicit versions. PMID- 1447551 TI - Memory with and without awareness: performance and electrophysiological evidence of savings. AB - Event-related potentials (ERPs) recorded on the scalp were shown to be sensitive indicators of the strength of a memory trace on both implicit and explicit tests of memory. In explicit recognition tests, the amplitude of a positive potential identified as P300 was larger for "old" than for "new" words regardless of whether the subject categorized the items correctly. This effect, however, was statistically reliable only when the recognition memory (d') was relatively high. In contrast to ERPs, the reaction times in explicit recognition were sensitive to accuracy but not to repetition. In implicit tests, lexical decisions to repeated words were faster than to newly presented words. The magnitude of the repetition effect varied neither with elapsed time since the last repetition nor with the number of previous repetitions. In contrast, the P300 elicited by the same words were sensitive to both lag and recency of repetition, suggesting that they were influenced by the episodic memory strength of the items. PMID- 1447552 TI - Direct and indirect measures of memory for modality in young and older adults. AB - In 2 experiments, young and older adults demonstrated modality effects of similar magnitude in perceptual identification tasks. That is, both young and older adults demonstrated more repetition priming when study and test modalities matched than when they were different, suggesting that contextual information was equally available across age. However, when asked explicitly to retrieve modality information, older adults were less accurate than young adults. These results constitute evidence for a dissociation between direct and indirect measures of memory for modality information. They call into question hypotheses that memory impairment in old age is due to deficient encoding of contextual information and challenge current accounts of modality effects in repetition priming. PMID- 1447553 TI - Aging and memory for expected and unexpected objects in real-world settings. AB - Adult age differences in the consistency effect were examined in 3 experiments. The consistency effect refers to items inconsistent with expectations being better remembered than items consistent with expectations. Younger and older adults walked into an office room and viewed objects that varied in their consistency with expectation. Immediate and delayed recognition tests on item information (i.e., distractors were defined by their semantic identity) revealed that both age groups recognized unexpected items better than expected items. However, when recognition of token information was requested (i.e., distractors were defined by their physical appearance), younger adults, in contrast to older adults, exhibited consistency effects. Also, under divided attention, young adults revealed the same pattern of data as did elderly adults under full attention. The results are discussed in terms of capacity-related differences in distinctive encoding. PMID- 1447554 TI - Improving recall by recoding interfering material at the time of retrieval. AB - Our experiments demonstrate that interference of an interpolated list of items with recall of an original list can be substantially reduced by forming Ss just before testing how to reorganize and simplify the interpolated material. In Experiments 1 and 2, Ss better recalled an initial serial list of letters when informed at testing that an interpolated list spelled a certain phrase backward. Similarly, in Experiments 3 and 4, Ss better recalled an initial list of cities when told that the interpolated cities were also names of former U.S. presidents. Control experiments rule out several simple explanations. In contrast to an editing hypothesis, the postorganizing clue helped recall even when problems of list differentiation were minimized. Current memory models appear unable to explain this benefit of a postlearning clue that enables Ss to segregate the interpolated material from the to-be-remembered material. PMID- 1447555 TI - Intratesticular control of spermatogenesis in the frog, Rana esculenta. AB - Adult intact and hypophysectomized (PDX) frogs, Rana esculenta, were treated with a gonadotropin releasing hormone agonist (GnRHA, HOE 766) and/or cyproterone acetate (CPA), the antiandrogen, in order to investigate the regulation of primary spermatogonial (I SPG) multiplication in vertebrates. Treatment with GnRHA (injections containing 900 ng administered for 12 days on alternate days) caused a significant increase of the mitotic index (MI) of I SPG in PDX animals and a further MI increase of SPG was observed when 0.66 mg CPA was given concomitantly with GnRHA. The treatment with 0.66 mg CPA in combination with GnRHA also increased secondary spermatocyte (II SPC) appearance. Moreover, number of nests containing spermatids (SPT) decreased as CPA, in combination with GnRHA, was administered in increasing doses (0.33 and 0.66 mg/injection). Intact animals treated with CPA (0.66 mg/injection) showed a time-dependent I SPG multiplication increase which reached highest values after 28 days. Secondary SPC also proliferated until day 28; meanwhile the number of nests containing SPT decreased. Neither testosterone nor R5020 (a progestin which is not converted to androgens) modified the basal and GnRHA-induced spermatogonial proliferation. These results confirm that in the frog, Rana esculenta, spermatid formation is impaired by CPA treatment and that I SPG multiplication is enhanced by a direct effect of GnRHA; moreover, we suggest that the absence of spermatids constitutes a signal promoting spermatogonial proliferation. PMID- 1447556 TI - Analysis of puberty-accelerating pheromones. AB - Two experiments were performed to test putative puberty-accelerating pheromones. In the first experiment, 37 weanling female house mice of the ICR strain were exposed to 1 of the following 3 treatments: an airborne mixture of 0.05 M isoamylamine and 0.05 M isobutylamine, fresh male mouse urine, or distilled water, as the control. Neither the amine mixture nor the male urine accelerated first estrus in the mice following airborne exposure to these compounds. In the second experiment, 37 weanling female mice of the same strain were exposed to the same chemicals as in the first experiment by direct contact to the oro-nasal groove. The mixture of isoamylamine and isobutylamine did not accelerate puberty, but direct contact with the male urine accelerated puberty as evidenced by uterine weights. PMID- 1447557 TI - Changes in brain gonadotropin-releasing hormone, plasma estradiol 17-beta, and progesterone during the final reproductive cycle of the female sea lamprey, Petromyzon marinus. AB - Changes in ovarian morphology, brain gonadotropin-releasing hormone (GnRH), plasma estradiol, and progesterone were examined during the 1988 and 1989 spawning migrations of the adult female sea lamprey, Petromyzon marinus. There were significant increases through time in brain GnRH (1989) and plasma estradiol (1988 and 1989), with progesterone levels fluctuating (1988 and 1989) during the freshwater phase of the spawning migrations. In 1989, brain GnRH and plasma estradiol levels gradually increased through time until just prior to spawning when levels decreased. During 1988, there were no significant changes in GnRH, which may reflect lower temperatures in that year. These data provide new information on brain GnRH during the final maturational processes in the female sea lamprey. PMID- 1447558 TI - Effects of an augmented nerve supply on forelimb regeneration in the adult mud frog, Rana rugosa. AB - Forelimbs of the adult mud frog Rana rugosa, when amputated midway through the zeugopodium, regenerate heteromorphically. The resulting regenerative outgrowths were mostly rod shaped and consisted of a cartilaginous core, in which the base was ossified, and muscle elongated distally along the cartilage, the whole being covered by connective tissue and skin. The tip of the regenerating muscle reached a point distally about one third of the length of the regenerative outgrowths. When the innervation of forelimb stumps was augmented by surgical diversion of the ipsilateral sciatic nerve, the amputated limbs regenerated mostly as spatula shaped outgrowths, which were longer than those of normally innervated forelimbs. Such hyperinnervated regenerates exhibited less ossification of cartilage, or sometimes none at all. However, the regeneration of muscle was more extensive. That is, it reached more than half way along the regenerative outgrowth. Furthermore, denervation resulted in the absence of regeneration in all cases examined. These results clearly indicate that limb regeneration in Rana rugosa is dependent upon the degree of innervation, not only for the early stages of regeneration, but also for the growth and differentiation of the regenerative outgrowth. PMID- 1447559 TI - Sustained attention and the Type A behavior pattern: the effect of daydreaming on performance. AB - The present study examined the ability of Type A and Type B subjects to sustain attention during a 40-min visual vigilance task. It was predicted that Type A subjects would perform better than Type B subjects and that the performance of both groups would be related to the frequency of daydreams during the vigil. Type A subjects outperformed Type B subjects with regard to perceptual sensitivity (A') and number of signal detections. Although both groups reported an increase in the number of their daydreams as the vigil progressed, Type A subjects reported fewer daydreams during each period of watch than did Type B subjects. In addition, an inverse relationship was found between the number of signal detections and the frequency of daydreams. PMID- 1447560 TI - Effects of spatial disruptions on reading speed for fast and slow readers. AB - Forty-five subjects read three paragraphs at their normal reading speed and were timed. The first paragraph was presented normally, and the others were shown either with spaces that had been filled in or with spaces that were randomized in size. The subjects' initial reading speed declined with both alterations, but to a greater extent with the filled text. Moreover, the reduction in reading speed was greater for the 10 fastest readers than for the 10 slowest readers. This pattern of performance may reflect a floor effect with slower readers in the filled condition, but the authors interpreted the results as providing further support for Hochberg's peripheral search guidance (PSG; 1970) stage of reading. PMID- 1447561 TI - Effects of same-modality interference on immediate serial recall of auditory and visual information. AB - Two studies investigated the effects of same-modality interference on the immediate serial recall of auditorily and visually presented stimuli. Typically, research in which this task is used has been conducted in quiet rooms, excluding auditory information that is extraneous to the auditorily presented stimuli. However, visual information such as background items clearly within the subject's view have not been excluded during visual presentation. Therefore, in both the present studies, the authors used procedures that eliminated extra-list visual interference and introduced extra-list auditory interference. When same-modality interference was eliminated, weak visual recency effects were found, but they were smaller than those that were generated by auditorily presented items. Further, mid-list and end-of-list recall of visually presented stimuli was unaffected by the amount of interfering visual information. On the other hand, the introduction of auditory interference increased mid-list recall of auditory stimuli. The results of Experiment 2 showed that the mid-list effect occurred with a moderate, but not with a minimal or maximal, level of auditory interference, indicating that moderate amounts of auditory interference had an alerting effect that is not present in typical visual interference. PMID- 1447562 TI - Induced arousal and orienting tasks as determinants of intentional recall. AB - In this study, the author examined the effects of intention to learn, noise, and different types of orienting tasks on short-term and long-term recall for 15 Hindi paired-associates. Intention to learn improved recall, as did encoding of semantic features, and noise impaired both short-term and long-term recall. The analysis of short-term recall scores indicated that there were no significant interactions between these factors, but the analysis of long-term recall scores indicated that there were significant interactions between noise and orienting tasks and between intentionality and orienting tasks. PMID- 1447563 TI - Pictures as a means of conveying information. AB - These two experiments, which were conducted at a large midwestern American university, demonstrated that naive art observers can recognize tangible objects that are represented realistically in a picture. However, naive art observers cannot perceive the abstract themes that are portrayed in a picture unless they are informed about the relationships between the pictorial symbols and the concepts they represent. PMID- 1447564 TI - Hypermnesia using auditory input. AB - The author investigated whether hypermnesia would occur with auditory input. In addition, the author examined the effects of subjects' knowledge that they would later be asked to recall the stimuli. Two groups of 26 subjects each were given three successive recall trials after they listened to an audiotape of 59 high imagery nouns. The subjects in the uninformed group were not told that they would later be asked to remember the words; those in the informed group were. Hypermnesia was evident, but only in the uninformed group. PMID- 1447565 TI - Null effect of mood as a semantic prime. AB - Semantic tasks, such as lexical decision making and word recognition, have not produced a mood priming effect. Earlier studies have been criticized because they included (a) mood induction techniques that required instruction to feel the mood, and (b) the use of overlearned tasks that did not require controlled processing. In this pair of experiments, the authors attempted to address these criticisms. However, the results of this study did not demonstrate a mood priming effect for happy and sad subjects who appraised sentence content as being happy or sad. The results of this study supported the dissociation of semantic and episodic memory. PMID- 1447566 TI - NMR investigations of Mn(II)-leucine-enkephalin complexes in [2H6]-DMSO solution. AB - Structural and kinetic features of the Mn(II)-Leu-enkephalin binding equilibria were delineated by measuring 13C and 1H NMR spin-lattice relaxation rates. The temperature dependence of such rates showed that some carbons were experiencing slow exchange regimes such that kinetic parameters at room temperature could be calculated (k(off) = 1400 sec-1, delta H* = 12.0 kcal/mol, delta S* = -9.9 e.u.). The paramagnetic rates of fast exchanging carbons were interpreted by the Solomon Bloembergen-Morgan theory to provide structural parameters. The terminal carboxyl and amino groups were shown to be the binding sites. The motional correlation time (tau c = 0.6 nsec at 298 K) was calculated by measuring selective and double selective 1H spin-lattice relaxation rates for the free peptide. The number of coordinated ligands was evaluated by considering the distance of the Leu CO in the complex at 2.54 A, as shown by molecular models. Finally, carbon-Mn(II) distances were calculated and the molecular model of the 1:1 complex was built. PMID- 1447567 TI - Siderophore-mediated iron (III) transport in the mycelia of the cultivated fungus, Agaricus bisporus. AB - Three structurally diverse iron (III) sequestering compounds (siderophores) were isolated from the supernatants of early stationary phase iron-deficient cultures of vegetative mycelia of the cultivated mushroom, Agaricus bisporus (ATCC 36416). The compounds were purified as their ferric chelates to homogeneity by gel permeation, cation exchange, and low-pressure reversed phase C18 chromatographies, and characterized as trihydroxamic acids. The chelates were identified as ferrichrome, ferric fusarinine C, and an unusual compound, des (diserylglycyl) ferrirhodin (DDF) by HPTLC cochromatography and electrophoresis against authentic samples, hydrolysis and amino acid analysis, and FAB-MS and 1H NMR spectroscopy. The iron transport activities of the three compounds (and of some structurally similar exogenous compounds) in young mycelial cells were determined by time- and concentration-dependent kinetic assays and inhibition experiments (CN-, N3-) using 55Fe(3+)-labeled chelates. 55Iron (III) uptake mediated by all three compounds was found to be via high affinity, energy dependent processes; transport effectiveness was in the order: ferrichrome > DDF >> ferric fusarinine C. The relative uptake of iron by lambda-cis ferrichromes was: ferrichrome > ferrirhodin >> ferrichrome A; transport activity by the delta cis fusarinines was: ferric fusarinine C > tris cis-(and trans-) fusarinine iron (III) >> ferric N1-triacetylfusarinine C. PMID- 1447568 TI - Inactivation of yeast phosphoglycerate kinase by Cr-ATP complexes and its implications on the conformation of the enzyme active site. AB - Exchange-inert beta, gamma-bidentate Cr(H2O)x(NH3)y ATP complexes inactivate yeast phosphoglycerate kinase (PGK) by forming a coordination complex at the enzyme active site. The observed inactivation rates ranged from 0.019 min-1 to 0.118 min-1 for Cr(NH3)4ATP and Cr(H2O)4ATP, respectively. Incorporation of one mol of Cr-ATP to the enzyme was sufficient for complete inactivation of the enzyme. The presence of Mg-ATP protected the enzyme against inactivation by Cr ATP. The other substrate 3-phosphoglycerate (3-PGA), when present, reduced the observed inactivation rates. The reduction of the k(obs) by 3-PGA was proportional to the number of NH3 ligands present in the coordination sphere of Cr3+ in the Cr-ATP complex, suggesting that in the ternary enzyme-Cr-ATP-3-PGA complex 3-PGA may be coordinated to the metal ion. When the effector sulfate ion was present, the presence of 3-PGA did not cause any further effects on the observed inactivation rates. This suggests that bound substrates are in a different arrangement at the active site when sulfate is present and therefore 3 PGA may not need to displace a ligand from Cr3+. Additionally, PGK exhibited a stereoselectivity for the binding of Cr(H2O)4ATP. delta diastereomer of Cr(H2O)4ATP yielded an order of magnitude smaller Ki value compared to the value observed with the lambda isomer. The recovery of enzyme activity was observed over a period of a few hours upon removal of excess Cr-ATP. The presence of substrates and/or effector ion sulfate did not alter the observed reactivation rate. There was no difference in the reactivation rates of the enzyme which was inactivated with Cr(H2O)4ATP or Cr(NH3)4ATP with and without 3-PGA. Increasing the ligand exchange rates of Cr3+ of Cr-ATP by increasing the pH value of the recovery medium from 5.9 to 6.8 increased the rate of recovery by a factor of 8. The pH dependence of the reactivation indicated that one hydroxyl group is involved in the recovery of the enzyme activity in enzyme CrATP and enzyme.CrATP.3-PGA complexes. PMID- 1447569 TI - Synthesis and characterization of N-methyliminodiacetato trans-R,R-, trans-S,S-, and cis-1,2-diaminocyclohexane platinum (IV) complexes: crystal structure of chloro(trans-R,R-1,2-diaminocyclohexane) (N-methyliminodiacetato) platinum(IV) chloride. AB - The compounds, chloro(trans-R,R-1,2-diaminocyclohexane) (N methyliminodiacetato)platinum(IV) chloride, chloro(trans-S,S-1,2 diaminocyclohexane)(N-methyliminodiacetato) platinum(IV) chloride, and chloro(cis 1,2-diaminocyclohexane)(N-methyliminodiacetato)platinum (IV) chloride, were prepared and characterized by elemental analysis, IR, and 195Pt NMR. The crystal structure of one of these three compounds, chloro(trans-R,R-1,2 diaminocyclohexane) (N-methyliminodiacetato) platinum(IV) chloride, was determined by x-ray single crystal diffraction. This compound is particularly interesting because the 1,2-diaminocyclohexane (DACH) ring is in a twist-boat configuration rather than the chair configuration previously reported for other DACH platinum compounds. The crystal structure consists of two independent cations and anions, with all atoms between these two independent molecules (except those in the chiral DACH) related by a pseudo-inversion center. Both platinum atoms have slightly distorted octahedral coordination, with angles ranging from 81.8 to 100.8 degrees. Crystallographic details: space group P2(1) (monoclinic); a = 19.864(5) A, b = 7.026(2) A, c = 12.446(3) A, beta = 106.64(2) degrees; Z = 4; R = 0.036 for 2333 reflections. PMID- 1447570 TI - Hallervorden-Spatz disease: clinical and MRI study of 11 cases diagnosed in life. AB - The diagnosis of Hallervorden-Spatz disease (HSD) has usually been made post mortem, although the recent description of characteristic abnormalities in the globus pallidus has suggested the possibility of an in vivo diagnosis. We present the clinical histories, neurological features and MRI findings of 11 patients, diagnosed as having HSD. Generalized dystonia with predominance of oromandibular involvement, behavioural changes followed by dementia and retinal degeneration were present in all the patients. MRI pallidal abnormalities consisted of decreased signal intensity in T2-weighted images, compatible with iron deposits, and of a small area of hyperintensity in its internal segment ("eye of the tiger" sign). We propose that the combination of these neurological signs with these MRI findings could be considered as highly suggestive of a diagnosis of HSD in living patients. PMID- 1447571 TI - Abnormalities of cerebral blood flow in the acute phase of bacterial meningitis in adults. AB - The frequency, course and clinical significance of changes in regional cerebral blood flow (rCBF) during bacterial meningitis were investigated in 14 adult patients. The results of 99mTc-hexamethylpropylene amine oxime (HMPAO) single photon emission computed tomography (SPECT) were compared with the clinical signs and findings using cerebral angiography and conventional CT. HMPAO SPECT was performed 2-15 days (median 4.5 days) after the onset of neurological disease. Decreased HMPAO accumulation was detected in 13 patients. SPECT studies revealed focal hypoperfusion corresponding to the clinical symptoms in 6 patients suffering from hemiparesis or hemiataxia. Conventional cranial CT disclosed brain infarction in only 1 patient. Focal hypoperfusion was also found in 7 of 8 patients without clinical evidence of focal neurological deficits. In 6 patients, HMPAO SPECT findings were abnormal although cerebral angiography was normal. At follow-up examinations 3-45 weeks after the acute disease, abnormalities revealed by HMPAO SPECT had improved or had even disappeared in all patients studied. Our results indicate that reduced rCBF is a frequent finding in bacterial meningitis in the adult. In most patients it probably represents a functional and reversible disorder without structural lesion detectable on CT. PMID- 1447573 TI - A new way to use the Ishihara test. AB - The Ishihara plates are widely used as a test for colour vision. Originally designed for the purpose of detecting congenital red-green colour blindness, the test also has some value in demonstrating acquired colour vision defects. There are, however, several disadvantages in the present arrangement of the plates. A modification of the test, involving the rearrangement of the order of the plates, is presented which, together with a new recording chart, simplifies both the administration and the interpretation of the test. PMID- 1447572 TI - Dementia in cerebral amyloid angiopathy: a clinicopathological study. AB - Dementia is in addition to cerebral haemorrhage major symptom of cerebral amyloid angiopathy (CAa). In order to explore the pathological basis for dementia in CAa related conditions, we made a clinicopathological analysis of CAa, with special attention to dementia. Among 150 patients (mean age 78.6 years) with autopsy proven intracranial haemorrhage in Tokyo Metropolitan Geriatric Medical Center, CAa with cerebral haemorrhage accounted for 8.0% (12 cases), associated with hypertension and metastatic brain tumour. Among 38 patients with lobar haemorrhage, CAa represented the second most common cause (21.1%) of intracranial haemorrhage after hypertension. A total of 20 patients with CAa (mean age 82.5 years) were studies clinically and pathologically. Hypertension was present in 50%. Thirteen had a history of stroke and others had either ill-defined or no strokes. The average number of strokes 2.9. Fifteen patients (75%) had dementia. Based on the clinicopathological grounds for dementia, CAa-related conditions could be divided into three subtypes: "haemorrhagic", "dementia-haemorrhagic" and "dementia" type. Haemorrhagic type (30%, 6 cases) showed multiple recurrent lobar haemorrhages caused by CAa. Hypertension was present in only 1 patient. The incidence of senile plaques and neurofibrillary tangles was generally correlated with age. Only 1 patient had dementia. The dementia-haemorrhagic type (40%, 8 patients) had recurrent strokes with cerebral haemorrhage after preceding dementia. There were two different neuropathological subsets: CAa with atypical senile dementia of Alzheimer type (SDAT) and CAa with diffuse leucoencephalopathy. Patients with CAa with atypical SDAT had multiple cerebral haemorrhages caused by CAa combined with atypical Alzheimer-type pathology. Patients with CAa with diffuse leucoencephalopathy had cerebral haemorrhages in combination with diffuse white matter damage like Binswanger's subcortical vascular encephalopathy (BSVE). The incidence of senile changes correlated with age. Patients with the dementia type (30%, 6 patients) showed progressive dementia with or without haemorrhage. All had hypertension. They had a combined condition of Alzheimer-type pathology with conspicuous CAa with BSVE. Dementia in CAa-related conditions may be responsible for multiple factors including not Alzheimer-type degeneration, but also diffuse leucoencephalopathy like Binswanger's disease. We also found an asymptomatic type, an ischaemic type, a vasculitis type and an hereditary type in this condition. PMID- 1447574 TI - Ganglioside antibodies: a lack of diagnostic specificity and clinical utility? AB - Serum IgG and IgM antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b and GT1b were determined in 210 patients with different degenerative and inflammatory disorders including motor neuron diseases, peripheral radiculopathies and neuropathies, multiple sclerosis and neuroborreliosis. No single disorder was associated specifically with ganglioside antibodies. No characteristic patterns of ganglioside antibodies were observed in any disease category. However, 32% of all patients had pathological antibody titres to at least one ganglioside. Four patients had pathological IgG and IgM titres for all gangliosides evaluated. They suffered from systemic lupus erythematosus [2], neuroborreliosis and schizophrenia, respectively. The results of this study indicate that the introduction of ganglioside antibody determination as a differential diagnostic test in clinical neurology is only helpful in a few patients with typical lower motor neuron syndromes. PMID- 1447575 TI - Gadolinium-enhanced magnetic resonance imaging of the central nervous system in systemic lupus erythematosus. AB - Gadolinium (Gd)-DTPA enhanced magnetic resonance imaging (MRI) was performed in 15 systemic lupus erythematosus patients with past (12) or present (3) features suggesting central nervous system (CNS) involvement. Symptomatic Gd-DTPA enhancing lesions were seen in 2 patients, and immunosuppressive treatment was associated with a rapid reversal of enhancement. The pattern of enhancement was different from that usually seen in multiple sclerosis. Gd-DTPA enhanced MRI may sometimes be useful in demonstrating the activity of CNS lupus. PMID- 1447576 TI - Amplification and expression of the epidermal growth factor receptor gene during the progression of neuroepithelial tumours in vivo. AB - The epidermal growth factor receptor (EGFR) gene is homologous to the oncogene c erbB. The occurrence of amplification and rearrangements at the EGFR gene locus is associated with malignancy in neuroepithelial tumours. Sixteen neuroepithelial tumours from eight patients with recurrence of their neoplasms were analysed for changes at the EGFR gene locus and for expression of EGFR. Ten tumours from five patients lacked changes at the EGFR gene locus. Three of eight individuals showed EGFR gene amplifications in both tumours with a higher grade of amplification in the second tumour. In addition to amplification, a rearrangement was found in both tumours of the first patient. In the second case an amplification of chromosome-7-specific c-met sequences was found in the regrown tumour, suggesting that a polysomy 7 was at least partly responsible for the higher copy number of the EGFR sequences. In both tumours of the third patient with EGFR gene amplification different alleles were amplified. In contrast to the findings at the DNA level the EGFR expression, analysed by immunohistochemical techniques, showed a more heterogeneous pattern after tumour progression. PMID- 1447577 TI - PCR detection of HIV proviral DNA in the brain of an asymptomatic HIV-positive patient. PMID- 1447578 TI - Suppression of experimental autoimmune encephalomyelitis by a new specific leukotriene biosynthesis inhibitor. PMID- 1447579 TI - "Cardiovascular effects of cocaine". PMID- 1447580 TI - Changing interpretations of angina pectoris associated with transient myocardial ischemia. AB - Silent ischemia associated with transient myocardial ischemia is currently recognized in the medical literature as a critical physiologic event that may occur in the absence of angina pectoris. A changing view of the clinical significance of angina pectoris as a reliable marker of myocardial ischemia is presented as a phenomenon of concern to nursing that carries implications for patient assessment, nursing interventions, and effectiveness of the nursing care. PMID- 1447581 TI - Chronic arterial occlusive disease. AB - Cardiovascular disease continues to be a major cause of death in the United States. Although the number of deaths has decreased in the past several years, disability from the disease remains significant because of its systemic nature. As the population continues to age, peripheral vascular disease (PVD) will become increasingly prevalent in society as a result of the process of atherosclerosis. This article focuses on the care of patients with PVD. Risk factors, presenting signs and symptoms, and diagnostic and therapeutic modalities associated with chronic arterial occlusive disease, as well as nursing responsibilities and interventions, are discussed. PMID- 1447582 TI - Coronary atherectomy: overview and implications for nursing. AB - Coronary atherectomy, a new invasive procedure for the treatment of atherosclerotic heart disease, consists of the excision and removal of atherosclerotic tissue from coronary artery walls. This article provides current information on atherectomy, including its potential advantages over percutaneous transluminal coronary angioplasty (PTCA). Indications, limitations, medical research, and implications for nursing research are described. A case study is presented. PMID- 1447583 TI - Intracoronary stents: a new approach to coronary artery dilatation. AB - Percutaneous transluminal coronary angioplasty (PTCA) is a low-risk treatment for proximal and localized coronary artery disease. Two major complications associated with angioplasty are abrupt closure and restenosis of the treated vessel. Abrupt closure requiring intervention occurs in approximately 3.6% of patients; the average restenosis rate reported in the literature is 30%. These difficulties can produce profound hemodynamic compromise requiring additional intervention. PTCA research focuses on methods to treat or prevent abrupt closure and restenosis of the stenotic segment. One new approach to this goal is the use of intracoronary stents after balloon angioplasty to maintain the luminal diameter of the coronary artery. The effectiveness of intracoronary stents is currently being evaluated. This article describes the purpose and design of intracoronary stents and reviews clinical trial results and nursing management of patients with such stents. PMID- 1447584 TI - A comparison of two techniques of care for indwelling arterial introducers after coronary angioplasty. AB - To determine whether indwelling arterial introducers can be maintained for 24 hours without risk of infection and/or hemorrhage in the post-coronary angioplasty patient, 96 patients were assigned to one of two groups. Introducers of the subjects in group I were flushed with 500 U of heparin, capped, and covered with a sterile occlusive dressing. Introducers of subjects in group II were connected to a heparinized (500 U in 500 mL normal saline) and pressurized (200 to 300 mm Hg) flush device. All introducers were removed 24 hours after coronary angioplasty. Results of t tests showed no significant difference between the two groups in incidence of infection or hemorrhage when hemoglobin, hematocrit, partial thromboplastin time, and white blood cell count were compared. Signs of inflammation at the introducer site (redness and swelling) and temperature elevation > or = 37.8 degrees C were not significantly different between the two groups. The incidence of hematoma formation at the introducer site was 40% in both groups. The two methods were found to be equally effective in maintaining a patent arterial introducer without risking infection and/or hemorrhage in the post-coronary angioplasty patient whose introducer remains indwelling for 24 hours. PMID- 1447585 TI - Effect of concurrent chest pain assessment on retrospective reports by cardiac patients. AB - The purpose of this study was to examine the effect of a concurrent record of chest pain episodes on later completeness and accuracy of verbal recall. Patients included 23 men and eight women, ages 43 to 76 years from a private cardiology practice who were randomized into experimental (n = 16) and control (n = 15) groups. Following an initial interview, experimental patients were instructed in using a Chest Discomfort Diary in the home setting to record eight categories of information about each episode of chest pain experienced during the next 7 to 10 days. At the end of that time, both groups were interviewed about a specific typical episode of chest pain that had occurred; patients who did not have chest pain during the study period described an episode experienced prior to the initial interview. Experimental patients recalled their chest pain more completely than controls (P = 0.007), whether it had occurred during or prior to the study period. Experimental patients who had pain (n = 11), and thus actually used the diary, accurately recalled the duration, intensity, description, and treatment of the typical episode but were often inaccurate regarding their mood and the total number of episodes they had experienced. The findings suggest that a concurrent diary offers one method of teaching patients how to report their chest pain symptoms and may improve the completeness and accuracy of those reports. PMID- 1447586 TI - Coronary artery fistulas: a review and case study. AB - Coronary artery fistula is a congenital abnormality that can present with a variety of cardiovascular complications. This article presents a patient with a coronary artery fistula outlining the pathophysiology and course of hospitalization, with particular emphasis on nursing management of a patient with coronary artery fistula. PMID- 1447587 TI - Preparation for cardiac catheterization. AB - Cardiac catheterization is an invasive procedure often included in the medical evaluation of patients with ischemic heart disease. This article reviews one well designed study that examines various approaches for preparing adults for a cardiac catheterization. PMID- 1447588 TI - Warehouse workers' headache. PMID- 1447589 TI - Warehouse workers' headache. PMID- 1447590 TI - Occupational dermal myiasis. PMID- 1447591 TI - A report on a workshop on the National Institute for Occupational Safety and Health B reader certification program. AB - In September 1990, a 2-day workshop was held in Chicago to discuss the current status of the NIOSH B reader certification program and to suggest modifications and improvements. This is a summary report of the proceedings of that conference. PMID- 1447592 TI - The NIOSH B reader certification program. An update report. AB - Physicians trained in the use of the International Labour Office system for classification of radiographs of pneumoconioses who pass a competence test administered by the National Institute for Occupational Safety and Health are designated as B readers. The current certification and recertification examinations for qualification under the NIOSH B reader program are described. Details of the rationale and format of each examination are given, and information on candidates' scores provided for the years 1987-1990. PMID- 1447593 TI - To B-read or not to B-read. PMID- 1447594 TI - Work-related electrocutions involving portable power tools and appliances. AB - Portable power tools and appliances can be identified as the source of injury in approximately 9% of occupational electrocutions. A search of fatality records for 1984 through 1986 in National Institute for Occupational Safety and Health (NIOSH) and Occupational Safety and Health Administration (OSHA) data bases identified 102 electrocutions involving portable appliances and tools that used 110-volt AC and 33 deaths involving welding equipment, which usually operates on 220-volt AC or higher. Of these 102 deaths, 51 occurred in the construction industry, 13 in services, 13 in manufacturing, and 25 in other industries. Plumbing contractors (Standard Industrial Classification [SIC] 1711) had the largest number of deaths (15) in construction. Powered hand-tools were involved in 58 deaths, with electric drills (23) and saws (13) the two largest classes. Proper provision of ground-fault circuit interrupter protection, particularly at temporary work sites, could have prevented most of the deaths from 110-volt AC. Engineering controls for preventing electrocution from portable arc-welding equipment should be evaluated. PMID- 1447595 TI - Workers' attitude toward the occupational physician. AB - This article presents research findings concerning workers' perception and opinion of the occupational health service (OHS) in three different Dutch companies. Beside comparing the effect of company characteristics, we were able to relate a worker's evaluation of the OHS to employee variables such as health status. We conclude that workers see clear differences in the tasks and functions of the occupational physician compared with those of the curative physician. Relations with and dependence on management is considered to be self-evident. A negative evaluation of the OHS is mainly because of unclarity and uncertainty as to how the occupational physician combines his/her responsibility toward individual workers with his/her responsibility toward the company. Suggestions are made for improvement of the reputation and credibility of the OHS. PMID- 1447596 TI - Hydrofluoric acid dermal burns. An assessment of treatment efficacy using an experimental pig model. AB - There currently exist various opinions concerning the best therapy for managing hydrogen fluoride (HF) dermal burns. Previously reported animal studies designed to evaluate the efficacy of certain therapies are not completely convincing. Studies initially were conducted to develop a reliable animal model for assessing efficacy of treatment. Evaluation of several animal species, dosing regimens (HF concentrations, exposure periods), and application techniques showed that the most consistent and reproducible dermal lesions were produced with 38% HF applied to the skin of anesthetized pigs for exposures of 9, 12, or 15 minutes using Hill Top Chamber patches. Using this model, the efficacy of six clinically applicable treatments was assessed by subjectively scoring and statistically analyzing photographic and histopathological data obtained from treated and untreated control lesions. Photographic data analysis ranked treatments with respect to effectiveness as follows: iced Zephiran and 10% calcium acetate soaks--highly effective; 2.5% calcium gluconate gel, 5.0% calcium gluconate injection and iced Hyamine soaks--effective; 10% calcium gluconate injection--ineffective. Histopathological data analysis showed the topical treatments (2.5% calcium gluconate gel, iced Hyamine, or iced Zephiran soaks) to be most effective in reducing superficial epidermal damage, and the 5% calcium gluconate injection or 10% calcium acetate soaks to be beneficial to deeper tissues of the dermis and subdermis. Injection of 10% calcium gluconate was ineffective. This study suggests that the anesthetized pig model has good applicability for assessing efficacy of HF dermal burn therapies. In addition, it indicates that further experimentation with 10% calcium acetate soaks is warranted. PMID- 1447597 TI - Confined space fatalities in Virginia. AB - To better understand the frequency and characteristics of occupational confined space fatalities in Virginia, we reviewed death certificates, workers' compensation files, a Virginia Occupational Safety and Health Administration listing, and medical examiner records for all 50 fatalities (41 accidents) reported during 1979 to 1986. All fatalities were identified in medical examiner records (50), more than in any other source. The majority of decedents were male craftsmen, operators, or laborers less than 50 years old (mean 38). Drug screens of the 43 decedents tested were negative, with the exception of 2 cases where blood alcohol was detected (greater than or equal to 0.06%). Approximately 5% of "at work" civilian deaths (excluding plane, train, and motor vehicle fatalities) were confined space related. Virginia resident death rates per million employees were highest for shipbuilding and repair facilities (23.2), local government (8.9), and manufacturing other than shipbuilding (5.4%). Multiple fatalities occurred in 4 (10%) of the accidents, with 3 involving 2 fatalities each, and 1 accident involving 7 fatalities. Three fatalities (6%) were rescuers. Fifty nonfatal injuries of rescuers were known to have occurred in these accidents, 15 of co-workers and 35 of community rescue personnel (firefighters and rescue squad members). Approximately half the accidents occurred during the fourth quarter of the year and on a Thursday or Friday, and about one third occurred at night. The leading accident type was atmospheric condition, most commonly oxygen deficiency (33%) or the presence of carbon monoxide (20%). In 6 (40%) of the 15 accidents involving atmospheric condition, the toxic gas or oxygen deficiency was absent in the confined space at the time of entry.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447598 TI - The Milan Automated Neurobehavioral System. Age, sex, and education differences. AB - The Milan Automated Neurobehavioral System (MANS) has been used in field studies to measure effects of toxicants on the central nervous system. The battery has not been deemed appropriate in clinical settings because of the paucity of available norms. In this study, 236 (151 men, 85 women) healthy 39- to 94-year olds were given the MANS as part of a comprehensive neurobehavioral evaluation. The subtests were simple visual reaction time, digit symbol substitution, serial digit learning, and Benton visual retention. Age and years of education accounted for a significant proportion of the variance in all four subtests. In two of the subtests (simple visual reaction time and Benton visual retention) sex also accounted for a significant proportion of the variance. Age-, sex-, and years of education-specific normative values are presented for healthy persons aged 50 to 79 years. PMID- 1447599 TI - Respiratory effects from the inhalation of hydrogen chloride in young adult asthmatics. AB - Almost no human data exist from controlled studies using low levels of hydrogen chloride (HCl), and, with no existing HCl ambient standards in the United States, the need for human health effects research is evident. In this study, five female and five male 18 to 25-year-old asthmatic subjects were exposed to filtered air, 0.8 ppm and 1.8 ppm HCl while wearing half-face masks, during three separate 45 minute experimental sessions involving 15 minutes exercise (treadmill walking), 15 minutes rest, followed again by exercise. Baseline and postexposure pulmonary function measurements were taken including forced expiratory volume in 1 second (FEV1), forced expiratory volume (FVC), maximal flow at 50% of expired vital capacity (Vmax50), maximal flow at 75% of expired vital capacity (Vmax75), and total respiratory resistance as well as peak flow. Nasal work of breathing and oral ammonia levels also were measured preexposure and postexposure. No significant pulmonary effects were found at these HCl concentrations and exposure duration. Nasal power showed no significant differences between test atmospheres; however, in isolation a significant decrease (P less than .01) was found in measurements of inspiration with exposure to 0.80 ppm. Ammonia levels showed a significant rise postexposure after both concentrations of HCl (paired t test, (P less than .01)), not seen after air exposure. In summary, the asthmatic subjects in this study showed no adverse respiratory health effects of inhalation of low concentrations of HCl. PMID- 1447600 TI - Cholylglycine measured in serum by RIA and interleukin-1 beta determined by ELISA in differentiating viral hepatitis from chemical liver injury. AB - Serum bile acids have been shown to serve as useful indicators of liver disease. We have confirmed these findings and added an analysis of interleukin-1 beta (IL 1 beta) profiles to further differentiate viral hepatitis from toxic liver damage associated with exposure to vinyl chloride (VC) or trinitrotoluene (TNT). The frequency of elevated cholylglycine (CG) was 100%, 75%, and 37.5% in viral hepatitis, VC- and TNT-linked liver injury patients, respectively. The mean levels, expressed in micrograms/dL, were 578, 507, 142, and 65 in hepatitis B, hepatitis non-A non-B, VC and TNT liver injury patients, respectively. Thus, the CG test could detect viral hepatitis and, VC liver injury, and (less frequently) liver injury associated with exposure to TNT. The mean level of IL-1 beta in patients with hepatitis type B was 424 pg/mL and hepatitis non A non B was 384 pg/mL compared with a mean of 33-40 pg/mL in those with VC or TNT-linked liver disease. The IL-1 beta detection test proved further to be an important distinguishing parameter as it was 100% positive in patients with viral hepatitis but only 12.5% to 25% positive in patients with VC/TNT-induced liver damage. PMID- 1447601 TI - Influences on cigarette smoking quantity. Selection, stress, or culture? AB - The selection, job stress, and job culture models of the association between occupation and smoking quantity were empirically evaluated in a random sample of 556 employed smoking adults in Orange County, California. Almost three quarters of the sample were heavy smokers (20 or more cigarettes per day). The largest percent of heavy smokers were blue-collar workers (77%). Age, sex, ethnicity, and the industry in which one works were all associated with heavy smoking, implying that selection and culture models contribute to smoking behavior. For example, men had twice the odds of being heavy smokers than did women, and Anglos had almost two and a half times the odds of being a heavy smoker than did non-Anglos. Smokers employed in the service, financial, insurance, and retail industries were one fourth as likely to be heavy smokers as those employed in the public administration sector. Smokers employed in the public administration sector had the highest percent of heavy smokers (88.9%). Job stress was not associated with heavy smoking compared with light smoking. Smoking cessation and prevention programs should address the social and job cultures in which the behavior occurs. Job-culture models of intervention should include elements that focus on individual coping mechanisms involving susceptibility to social pressure; social environment models imply that change in organizational culture is necessary. PMID- 1447602 TI - The validity of study group assignments based on occupational histories obtained from questionnaires. AB - This study examined the validity of self-reported work histories for use in epidemiological studies of toxic exposures. Two uses that were examined were the assignment of subjects to exposure groups and the estimation of exposure duration. Questionnaire responses and data extracted from employment files were compared for 161 retired automobile workers. The questionnaire method assigned subjects to two extreme groups with 99% accuracy but rejected 30% of the subjects because of ambiguous data. Self-reports of exposure duration correlated moderately with the file estimates (r = .63, P = .01). The discrepancy between subjects' estimates and actual exposure duration correlated with subjects' job mobility. The findings indicate that the validity of self-report data declines with the precision required of the data, but that self-reports may have sufficient validity for studies that use extreme-group designs. PMID- 1447603 TI - The primary treatment of frontobasal and midfacial fractures in patients with head injuries. AB - The timing of operation can be especially difficult when frontobasal fractures are combined with other head injuries and midfacial injuries. In these cases, the head injury represents a considerable hazard to the patient and therefore it is mandatory to avoid any additional strain that might be caused by treating the midfacial injury first. On the other hand, because of poorer results with the secondary treatment, the surgical therapy for midfacial injuries should be achieved as early as possible. This report describes the results obtained in 68 patients managed over a period of 5 years and discusses their definite primary treatment. It emphasizes the need for close cooperation between the various surgical specialties involved. PMID- 1447604 TI - Cross-sectional tomography in evaluation of patients undergoing sagittal split osteotomy. AB - A study was performed to evaluate the possibility of locating the mandibular canal before sagittal split osteotomy by cross-sectional spiral tomography in 55 patients. Visibility of the whole canal wall circumference was excellent or good in 65.5% fair in 18.2%, and poor in 12.7% of cases. Only four canals (3.6%) were invisible. The canal was located lingually in 61 cases, buccally in 9 cases, and centrally in 34 cases. In patients with mandibular protrusion, the mean (+/- SD) buccolingual width was significantly smaller (9.5 +/- 1.51 mm vs 10.4 +/- 1.46 mm, P < .01) and the mandibular canal was more often buccally located than in patients with retrognathia. PMID- 1447605 TI - Marsupialization for treatment of oral ranula: a second look at the procedure. AB - Simple marsupialization to manage oral ranula has fallen into disfavor because of excessive failures and the high incidence of iatrogenically caused cervical ranula that may follow this procedure. With the simple addition of packing the entire pseudocystic cavity with gauze after its unroofing, the rate of recurrence is minimized. It is recommended that oral ranula be treated initially by marsupialization with packing and, if recurrence occurs, then the offending sublingual gland should be excised. PMID- 1447606 TI - Pediatric facial injuries associated with all-terrain vehicles. AB - All-terrain vehicles (ATVs) are becoming increasingly popular recreational devices. Multiple injuries have been associated with ATV accidents. This report reviews pediatric injuries treated at a regional pediatric trauma center, with special attention to facial trauma, as well as the ATV injury data for the United States. PMID- 1447607 TI - A preliminary study of maximum voluntary bite force and jaw muscle efficiency in pre-orthognathic surgery patients. AB - The functional state of dentofacial deformity patients before orthognathic surgery has received relatively little study. In this study, the ability to generate occlusal force was compared between 84 patients before treatment for various dentofacial deformities and 57 controls. Maximal and submaximal bite forces were measured at the incisor and right and left first molar bite positions. Electromyographic activity (EMG) was recorded bilaterally from the anterior temporalis, posterior temporalis, and masseter muscles during each bite. An efficiency ratio was calculated for the jaw muscles by dividing the level of EMG by the occlusal force. There was a reduced ability to generate occlusal forces in the patients before surgery, especially among female patients. The reductions in maximal occlusal force were correlated with reduced efficiency of the jaw muscles. PMID- 1447608 TI - The response of midfacial bone in sheep to loaded osteosynthesis screws in pretapped and nontapped implant sites. AB - This study compared the functional retention of pretapped and self-tapping 2-mm AO miniscrews (Stratec Medical, Waldenburg, Switzerland) in an animal experimental model. Histologic evaluation of the bone surrounding the loaded screws showed significantly more remodeling when pretapped screws were used than when self-tapping screws were used. Although the experimental situation may not be directly comparable with the clinical situation, this study does lend credibility to the assumption that pretapping is not advisable in the thin bone of the midface. PMID- 1447609 TI - In vitro strength analysis of sagittal split osteotomy fixation: noncompression monocortical plates versus bicortical position screws. AB - An in vitro study using bovine ribs was performed to compare the strength of monocortical plates with bicortical position screws. An osteotomy was created to simulate a sagittal split and a 5-mm bone gap was produced. Four study groups were created: screw nongap, screw with gap, plate nongap, and plate with gap. Parameters of strength were analyzed by elastic deformation, stiffness ratio, permanent deformation, and breaking load. The results showed that monocortical plate fixation in bovine ribs provides less rigidity and is more susceptible to deformation than is bicortical position screw fixation. PMID- 1447610 TI - Bone induction by composites of bioresorbable carriers and demineralized bone in rats: a comparative study of fibrin-collagen paste, fibrin sealant, and polyorthoester with gentamicin. AB - Host tissue response and heterotopic osteoinduction by composites of demineralized bone matrix and three different substances used as bioresorbable carriers implanted in the abdominal muscles were evaluated by strontium 85 uptake and histology 4 weeks postoperatively in 60 male Wistar rats. Both fibrin collagen paste and fibrin sealant inhibited bone induction and produced a chronic inflammation; part of the fibrin-collagen paste was still present at 4 weeks. Polyorthoester with gentamicin was almost completely absorbed, induced minimal tissue reaction, and did not inhibit osteoinduction. PMID- 1447611 TI - Healing of bony defects in the irradiated and unirradiated rat mandible. AB - A model system of the irradiated rat mandible has been developed and used in conjunction with a non-spontaneously healing mandibular defect. The contribution of the tissue components in the healing of bony defects was studied using demineralized bone powder (DBP) prepared from unirradiated or in vivo irradiated rat long bones. Better bony fill of the defects occurred in the irradiated beds filled with unirradiated DBP than in the unirradiated beds containing irradiated DBP. This suggests that, at least in the early postirradiation period, the bed is not the limiting factor in healing of bony defects and the osteogenic components of bone in the DBP may be most affected by irradiation. In the irradiated bed, the defects grafted 2 weeks after irradiation healed better than those grafted at 4 weeks. Thus, the timing of surgery after irradiation also plays a role in the healing process, with early surgery producing better results. PMID- 1447612 TI - Ketorolac tromethamine: an oral/injectable nonsteroidal anti-inflammatory for postoperative pain control. AB - Ketorolac tromethamine is a new injectable/oral nonsteroidal anti-inflammatory analgesic with no apparent opiate receptor activity that has been administered alone and in combination with other opiate analgesics for the treatment of postoperative pain. The drug has shown promise in analgesic comparisons with morphine sulfate; it lacks the effects of respiratory depression and nausea and vomiting usually associated with narcotic agents. Intramuscular ketorolac may be particularly useful with those patients who have respiratory disease and patients being dismissed following short ambulatory or private-office anesthetic procedures. PMID- 1447613 TI - Outcome assessment in oral and maxillofacial surgery advanced education programs. AB - Outcome assessments are becoming a standard by which predoctoral and postdoctoral advanced dental educational programs are being evaluated internally and externally. This article presents an overview of the process of development of an outcome assessment document for oral and maxillofacial surgery residency programs and provides an example of its value in the evaluation of two different types of oral and maxillofacial surgery programs. PMID- 1447614 TI - Posttraumatic facial swelling and draining sinus tract. PMID- 1447615 TI - Calcifying epithelial odontogenic tumor (Pindborg tumor): report of case. PMID- 1447616 TI - Calcifying epithelial odontogenic tumor of the maxillary sinus. PMID- 1447617 TI - Hemangiopericytoma of the parotid gland: report of case. PMID- 1447618 TI - Histopathologic findings in a case of recurrent parotitis in adulthood. PMID- 1447619 TI - Non-Hodgkin's lymphoma involving the inferior alveolar canal and mental foramen: report of a case. PMID- 1447620 TI - Osteomyelitis of the mandibular condyle: report of a case. PMID- 1447621 TI - Heterotopic gastrointestinal cyst of the oral cavity. AB - A case of an oral heterotopic gastrointestinal cyst of the tongue is described and a review of the literature is presented. The oral gastrointestinal cyst is a developmental lesion found more commonly in males, with a wide age range, but mostly occurring in the young. It presents as an asymptomatic swelling and most likely arises from misplaced embryonal tissue. Conservative surgical excision is the treatment of choice and no recurrence is expected. PMID- 1447622 TI - A lag screw technique for fixation of cranioplasty implants. PMID- 1447623 TI - A technique for fixation of oral mucosal lesions. PMID- 1447624 TI - Parameters of care--suggestions or requirements. PMID- 1447625 TI - Adverse food reactions in childhood: concept, importance, and present problems. PMID- 1447626 TI - Current status of digestive intolerance to food protein. AB - Digestive intolerance to food proteins may occur in childhood as a result of a wide range of etiologic and pathophysiologic mechanisms. Cow milk protein intolerance is the most common form of food intolerance in children. Food allergy and food intolerance may be confused because both produce similar symptoms, especially in young children with clinical manifestations of food allergy localized to the gastrointestinal tract. On the other hand, food-sensitive enteropathy may be defined as the clinical food-related syndromes associated with an abnormal small intestinal mucosa. Although several foods have been reported to damage the small intestinal mucosa in infancy (soy, rice, fish, chicken meat, egg), cow milk-sensitive enteropathy is the most common cause. Whatever the mechanisms, digestive intolerance to food proteins with or without enteropathy is primarily a temporary condition of infancy, in contrast to most forms of food allergy. In children with these disorders, symptoms usually resolve by 1 to 3 years of age. The variation in prevalence rates of this disorder in different countries can be explained by different diagnostic criteria. The classic food sensitive enteropathy syndromes with chronic diarrhea and failure to thrive in infancy have become rarer in some European countries, including Spain. Some risk factors for the development of these conditions appear to be early exposure to cow milk feedings, acute infectious diarrhea, and malnutrition. Breast-feeding appears to be at least partially protective. PMID- 1447627 TI - Cow milk-sensitive enteropathy: predisposing factors and treatment. AB - Cow milk-sensitive enteropathy is a temporary disorder of infancy characterized by a variably abnormal small intestinal mucosa while milk is in the diet. This abnormality is reversed by a cow milk-free diet, only to recur on challenge. Important predisposing factors are age (< 3 years), transient IgA immunodeficiency, atopy, and early bottle feeding. The disorder is diagnosed histologically by evidence of mild-to-moderate partial villous atrophy with thin, often patchy mucosa. For an accurate clinical diagnosis, challenge with the offending food after a demonstrated response to cow milk elimination is critical. When available, serial small intestinal bowel biopsies related to elimination and challenge are also important. Treatment is elimination of cow milk and all foods based on cow milk, and substitution of cow milk feedings with commercially available formulas free of cow milk protein. Five types of cow milk substitutes are described; only nutritionally complete formulas are recommended. Later, a milk challenge will determine the timing of safe reintroduction of cow milk to the diet, at a time when the child is gaining weight, thriving, and symptom free. This dietary treatment is always temporary; reintroduction of a normal diet is nearly always possible between 1 and 2 years of age. PMID- 1447628 TI - Cow milk allergy in infancy and hypoallergenic formulas. AB - Substitute feedings have been used to treat infants with cow milk protein allergy for most of this century. For the past 50 years, several infant formulas based on animal proteins, both intact and chemically modified, or on vegetable protein have been labeled "hypoallergenic." Because of the risk of anaphylaxis and other serious adverse reactions, formulas that are claimed to be hypoallergenic should be subjected to rigorous preclinical and clinical testing. At a minimum, such formulas should not provoke any allergic signs or symptoms in 90% of infants with documented cow milk protein allergy when tested in double-blind, placebo controlled trials. A standardized definition of "hypoallergenic" will allow clinicians and parents to understand the true risks to a cow milk-allergic infant fed such hypoallergenic formulas. PMID- 1447629 TI - Allergenicity of cow milk proteins. AB - The allergenicity and antigenicity of cow milk proteins are age dependent. Because the nonspecific and specific factors inhibiting the passage of cow milk proteins through the epithelial layer of the intestine are deficient at birth, although developing during early infancy, allergy to cow milk may be acquired during the first year of life. Allergic reactivity to cow milk is lost during childhood in the vast majority of cases. This change may depend at least partly on the development of the local immune system of the gut producing antigen specific IgA antibodies. Circulating IgG antibodies to cow milk proteins are always produced when an infant has cow milk in the diet but are not associated with allergy; their titer is reduced with age. Clinical challenge tests show that most cow milk-allergic patients react to several protein fractions of cow milk. A patient may have IgE antibodies to several fractions of cow milk, measured either by skin testing or by radioallergosorbent test. Likewise, various tests for cell mediated immunity may show positive reactions to several fractions. No single major allergen is apparent in cow milk, according to either the challenge tests or laboratory procedures: casein, alpha-lactalbumin, and beta-lactoglobulin all show a high proportion of positive reactions. PMID- 1447630 TI - Allergenicity and nutritional adequacy of soy protein formulas. AB - Soy protein formulas are used for different conditions, including cow milk protein allergy, lactose and galactose intolerance, and severe gastroenteritis. Feeding soy protein formulas to normal term infants is associated with normal growth, normal protein nutritional status, and normal bone mineralization. Recent studies of infants fed soy protein formulas exclusively during the first months of life revealed no immunologic abnormality; however, the use of such formulas for management of cow milk protein allergy and for prevention of atopy is controversial. Although in the past decade many studies have stressed soy allergenicity, soy allergenicity has been confirmed by the challenge test in only a few studies. In this article we review the studies dealing with the allergenicity of soy protein formulas. We also present our own data on their use in the prevention and management of cow milk protein allergy. PMID- 1447631 TI - Fish allergy: evaluation of the importance of cross-reactivity. AB - Fish constitute one of the most important groups of allergens in the induction of immediate (type I) food hypersensitivity. In our environment, fish allergy is present in 22% of all patients with a diagnosis of food hypersensitivity. We studied the allergenic significance of the fish species considered most representative because of their greater consumption in our environment (flatfishes: Pleuronectiformes such as sole, whiff, and witch; Gadiformes such as hake; and Scombriformes such as albacore) or because of the results of previous studies of Gadiformes such as cod. Through the use of isoelectric focusing and sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting, we have observed that several allergens common to all these species are able to bind specific IgE from the sera of sensitized patients. This allergenic community has been confirmed by radioallergosorbent inhibition. Another group of species specific allergens focuses in the regions at about pH 5 and with molecular weights less than 14 kilodaltons; these allergens correspond to sarcoplasmic parvoalbumins. From the results observed, which have been confirmed by various procedures and techniques, we conclude that hake is the fish with the capability to induce the strongest IgE response, followed by whiff; the witch seems to be the least allergenic of all flatfishes. Among all species studied, albacore was the least allergenic. These results may be considered when one introduces supplementary feeding with fish in infants, most particularly in infants at high risk for atopy. PMID- 1447632 TI - Summary and future directions. Adverse reactions to food in infancy and childhood. PMID- 1447633 TI - Nonclinical testing of formulas containing hydrolyzed milk protein. AB - The allergenic potential of cow milk-based infant formula can be reduced by protein hydrolysis. Controlled clinical studies are necessary to demonstrate conclusively the biologic efficacy of these formulations in human beings. Nonclinical testing programs provide manufacturers with the opportunity to characterize various molecular and immunologic properties of these hydrolysates and their corresponding final product forms. Physicochemical analyses provide data relating to the extent of protein hydrolysis and peptide molecular weight distribution. Immunochemical analyses can semiquantitatively estimate hydrolysate reactivity with preformed antibody. The ability of hydrolysate-based products to induce an immune response can be evaluated by using animal models. It is the responsibility of the manufacturer to choose the appropriate combination of nonclinical tests and use them to document product consistency, thus helping to ensure consistent clinical performance. PMID- 1447634 TI - Food-processing approaches to altering allergenic potential of milk-based formula. AB - All the major cow milk proteins in their native states are potential allergens in infants with milk allergy. Heat treatment can reduce the antigenicity of whey proteins considerably, but it has virtually no effect on the antigenicity of casein. Infants allergic to milk still react to heat-denatured whey proteins. Therefore heat denaturation alone cannot produce a formula with low allergenicity. Enzyme hydrolysis reduces the antigenicity and allergenicity of protein. Partial hydrolysis produces hydrolysate consisting mainly of large peptides, whereas extensive hydrolysis produces hydrolysate containing a mixture of large and small peptides and free amino acids. Enzyme hydrolysis often produces bitter peptides and destroys the physical functionality of protein. When hydrolysate formula is made, casein or whey protein hydrolysate is ultrafiltered to remove large residual peptides. Certain amino acids are fortified to provide a balanced amino acid profile. The final formulation must comply with the recommendations of the Codex Alimentarius Commission (FAO/WHO) and the U.S. Infant Formula Act to provide adequate infant nutrition. Protein hydrolysate based formula can be improved by further reducing the residual allergenicity, increasing the small peptide content, and improving the taste. PMID- 1447635 TI - Prediction and detection of allergy development: influence of genetic and environmental factors. AB - The prevalence of atopic diseases is increasing in northwestern Europe and probably also in the rest of the Western world. Detecting cord blood IgE, in combination with obtaining a family history of atopic disease, seems to be the most valuable method of predicting all forms of atopic disease; however, this will identify only a small proportion of children with subsequent development of atopic disease. Determination of cord blood IgE cannot, without modifications, be recommended as a single test for identifying infants for allergy prevention programs. Skin prick reaction to egg white during the first year of life seems to identify a majority of children in whom allergic disease is going to develop during infancy. Other methods, such as genetic markers of an atopic constitution, eventually may facilitate early identification of infants at risk of atopic disease. PMID- 1447636 TI - Definitions and diagnosis of food intolerance and food allergy: consensus and controversy. AB - This article describes the terms used for the various syndromes and diseases associated with reactions to foods; it outlines the principal types of food intolerance encountered in children, with particular emphasis on those caused by immune-mediated reactions of immediate hypersensitivity. Terms defined include food intolerance or food sensitivity; food allergy or food hypersensitivity; psychologically based food reactions (food aversions); and psychosocial and neurologic dysfunction. The spectrum of food sensitivity is considerable, and diagnosis is generally based on the monitoring of effects of exclusion diets and provocation tests, after appropriate objective measures are first selected. In children, manifestations of IgE-mediated food allergy (often in association with other immune mechanisms) include self-limiting and immediate reactions (e.g., urticaria, wheeze) and chronic diseases (food-sensitive enteropathies, eczema). Controversial and unresolved issues exist with some other conditions, including eosinophilic gastroenteritis, occult gastrointestinal bleeding, protein-losing enteropathy, and attention deficit disorder with hyperactivity. New methods for clinical investigation of gastrointestinal tract function and intestinal immune reactions are required to assess the relevance of foods in these conditions. PMID- 1447637 TI - Dietary manipulation and induction of tolerance. AB - Clinical observations have suggested that the development of atopic diseases in childhood may be influenced by breast-feeding and the timing of first exposure to foreign protein, but the controversy is far from being resolved. Early weaning and introduction of foreign proteins (i.e., cow milk) have been associated with an increased prevalence of atopic symptoms in infants with a family history of atopy. Opposite results have been reported, and the effects of early protein introduction in infants not at risk of having atopic symptoms are poorly documented. Research in rodents suggests that perinatal antigen exposure is more likely to prime the immune system than to induce tolerance. Continuous feeding beyond the critical neonatal period leads to induction of tolerance. The immunologic response is dependent on the antigen dose. Protein transfer by breast feeding can induce tolerance, though in a dose range otherwise associated with priming. The protective effect of antigen avoidance in infancy on the development of cow milk allergy and also on subsequent atopic symptoms is well documented. Protective effects have been observed in infants at risk who either were breast fed or received a hydrolyzed infant formula. Several clinical studies suggest a causative role of neonatal milk exposure in the development of cow milk allergy. Prospective, population-based studies are required to assess the true incidence of food-allergic diseases in childhood. PMID- 1447638 TI - Comparison of the residual allergenic activity of six different hydrolyzed protein formulas. AB - The residual allergenic activity of protein hydrolysates contained in marketed "hypoallergenic" infant formulas can be determined both by in vivo methods (skin prick tests, provocation tests) and by in vitro methods (radioallergosorbent test, radioallergosorbent inhibition, crossed radioimmunoelectrophoresis, basophil histamine release). In general, whey hydrolysates containing a high percentage of larger peptides have the highest capacity to induce positive skin test and provocation test results, and to bind to human serum IgE antibodies of cow milk-sensitive children. Casein hydrolysates appear to have very little residual allergenic activity. Before hypoallergenic formulas are prescribed for cow milk-sensitive children, individual testing (e.g., skin test, challenge tests) is recommended. PMID- 1447639 TI - Effects of brief early exposure to partially hydrolyzed and whole cow milk proteins. AB - Clinical experience ("the dangerous bottle") and experimental evidence indicate that the early life of an infant is particularly important for the development of the immune responses to food antigens. However, the clinical and immunologic consequences of a brief exposure to, or avoidance of, food antigens during the neonatal period in human infants are poorly understood and documented. We present the preliminary results of a prospective controlled study of 256 normal breast fed infants randomly assigned to receive (blind) either an adapted formula (Nidina) or a partially hydrolyzed formula (Nidal HA) as a supplement to breast feeding for a few days when necessary, and to be examined at days 5, 90, 150, and 365. The results indicated that (1) the prevalence of clinical symptoms and of total and specific IgE responses was not statistically different in the two groups of infants and (2) infants fed a hydrolyzed formula had median titers of specific IgG lower than those fed an adapted formula; the difference was significant for alpha-lactalbumin at day 90 (p < 0.005) and for alpha-lactalbumin (p < 0.05), casein (p < 0.05), and hydrolyzed formula (p < 0.01) at day 150. Humoral immune responses of breast-fed infants to food antigens thus appear to be modulated by early, short-term exposure to them. PMID- 1447640 TI - Effects of prolonged exposure to partially hydrolyzed milk protein. AB - Formulas containing proteins with reduced potential to sensitize might be effective in reducing the risk of atopic disease, but such products should be nutritionally adequate. We designed a randomized, double-blind study to evaluate nutritional adequacy and sensitization potential of a formula containing partially hydrolyzed whey-predominant milk proteins. Subjects were term infants enrolled at birth. Infants in group A were fed human milk, and group B received the partially hydrolyzed formula; group C, fed a formula containing intact whey predominant milk proteins, served as control subjects. We recorded anthropometric measurements and symptoms of formula intolerance at monthly intervals for 4 months in 205 infants. Milk IgE and IgG antibodies were measured until 8 months of age in 63 infants. Daily weight gain was not significantly different among the groups. Gastrointestinal symptoms attributed to feeding intolerance were also comparable. Increases in serum IgG antibodies were significantly greater in group C throughout the study. There were no significant differences in IgE antibodies. Thus a formula containing partially hydrolyzed whey-predominant milk protein promoted adequate growth and induced a lesser priming effect for IgG antibody response than did an intact whey-predominant formula. PMID- 1447641 TI - Long-term prevention of allergic diseases by using protein hydrolysate formula in at-risk infants. AB - This prospective, long-term study assessed the effects of a protein hydrolysate formula on allergy prevention in infants with a family history of allergy. Infants were randomly assigned to receive either the hydrolysate formula (n = 92) or an adapted cow milk formula (n = 85) alone or with breast-feeding for 4 months. The groups did not differ in family allergy history scores or cord blood IgE levels. After 4 months, total IgE levels and allergic reactions did not differ significantly between groups, although the hydrolysate group had a lower prevalence of eczema. At 12 months of age, neither IgE levels nor allergic reactions were significantly different. At 2 years of age, however, 18 allergic reactions had occurred in the hydrolysate group and 31 had occurred in the control group; the differences were significant for eczema (p < 0.001) but not for asthma. At 4 years of age, allergic signs were found in 11 children in the hydrolysate group and in 17 children in the control group; the difference was significant only for eczema (p < 0.01). These results suggest that early feeding of a protein hydrolysate formula to infants at risk for allergies had a long-term preventive effect on the prevalence of eczema but not of asthma. PMID- 1447642 TI - Relationship of cross-brain oxygen content difference, cerebral blood flow, and metabolic rate to neurologic outcome after near-drowning. AB - We evaluated the relationship of global cerebral blood flow, cross-brain oxygen content difference, cerebral metabolic rate for oxygen, intracranial pressure, and cerebral perfusion pressure to functional neurologic outcome in 12 comatose children on 2 consecutive days after near-drowning. Five children survived with functional neurologic outcome; five died and two survived with severe neurologic damage. Children who survived with functional neurologic outcome had a significantly higher cross-brain oxygen content difference (7.89 +/- 2.62 vs 3.91 +/- 1.59 ml/dl; p = 0.028) at 24 hours and a higher cerebral metabolic rate for oxygen 48 hours after admission (3.19 +/- 2.86 vs 0.96 +/- 0.45 ml/100 gm per minute; p = 0.030) compared with those who died or survived in a damaged state. There were no significant differences in global cerebral blood flow, intracranial pressure, and cerebral perfusion pressure between groups at either 24 or 48 hours. Our preliminary data suggest that a higher cross-brain content difference value is an important early variable associated with functional neurologic recovery after near-drowning. However, a single cross-brain oxygen content difference value must be interpreted with caution because considerable variability may occur among patient groups. PMID- 1447643 TI - Coma associated with intense bursts of abnormal movements and long-lasting cognitive disturbances: an acute encephalopathy of obscure origin. AB - We report six previously healthy children who several days after a prodromal illness had an acute encephalopathy that ran a biphasic course. It appears to constitute a recognizable syndrome with a good prognosis that can be differentiated from other encephalopathies of obscure origin as previously defined by Lyon et al. The active phase was dominated by coma or confusion and by abnormal movements, including disordered gesticulation and attacks of orofacial dyskinesia or limb dystonia associated with permanent rigidity and culminating in opisthotonic posturing. Repeated seizures were observed in only two patients. Permanent slow waves were recorded on the electroencephalogram in all patients, even during bursts of abnormal movements. Cerebrospinal fluid and results of serologic studies were normal throughout the course of the disease, and attempts at viral isolation and antiviral antibody detection yielded negative results. Brain imaging either showed no abnormalities or suggested a moderate degree of brain edema. The recovery phase, which extended for several weeks, was characterized by a rapid return of motor function and persistent behavioral and cognitive disturbances. Nonverbal reasoning recovered long before verbal expression returned to normal. Four patients eventually recovered fully, whereas two had mild sequelae. PMID- 1447644 TI - Concentration of milk secretory immunoglobulin A against Shigella virulence plasmid-associated antigens as a predictor of symptom status in Shigella-infected breast-fed infants. AB - We conducted a prospective, community-based study of healthy breast-fed Mexican infants to determine the protective effects of anti-Shigella secretory IgA antibodies in milk. Milk samples were collected monthly, and stool culture specimens were obtained weekly and at the time of episodes of diarrhea. Nineteen breast-fed infants were found to have Shigella flexneri, Shigella boydii, or Shigella sonnei in stool samples. Ages of the 10 infants with symptomatic infection and the nine with asymptomatic infection did not differ significantly. Milk samples collected up to 12 weeks before infection were evaluated by enzyme linked immunosorbent assay for secretory IgA antibodies against lipopolysaccharides of S. flexneri, S. boydii serotype 2, S. sonnei, and virulence plasmid-associated antigens. The geometric mean titers of anti-Shigella antibodies to virulence plasmid-associated antigens in milk received before infection were eightfold higher in infants who remained well than in those in whom diarrhea developed. The significance of milk secretory IgA directed against lipopolysaccharide was less clear. We conclude that human milk protects infants against symptomatic shigella infection when it contains high concentrations of secretory IgA against virulence plasmid-associated antigens. PMID- 1447645 TI - Comparison of acellular (B type) and whole-cell pertussis-component diphtheria tetanus-pertussis vaccines as the first booster immunization in 15- to 24-month old children. AB - We compared an acellular (B type) pertussis-component diphtheria-tetanus pertussis (DTP-Ac) vaccine containing equal amounts of filamentous hemagglutinin and lymphocytosis-promoting factor with a conventional whole-cell vaccine as the first booster immunization in 162 healthy children 15 to 24 months of age. Fewer local reactions (e.g., erythema, swelling, and tenderness at the injection site) were seen in DTP-Ac vaccine recipients during the first 48 hours of observation. This group also had fewer episodes of fever (> or = 38 degrees C) and other systemic reactions (e.g., irritability, drowsiness, and anorexia). Overall, 57% of the DTP-Ac vaccine recipients had no obvious adverse reactions, in contrast to 5% in the comparison group. At 4 to 8 weeks after vaccination, serum antibody responses to filamentous hemagglutinin and lymphocytosis-promoting factor were greater in recipients of the acellular vaccine as determined by an enzyme-linked immunosorbent assay. We conclude that this B-type acellular vaccine is both immunogenic and much less likely to cause an adverse reaction than a currently licensed whole-cell vaccine, and is suitable for routine booster immunizing doses to protect against pertussis. PMID- 1447646 TI - Risk factors for asthma in inner city children. AB - Inner city children have the highest prevalence and the highest mortality rates for asthma in the United States. The purpose of this study was to evaluate sensitization and exposure to common indoor allergens among children aged 3 years to 15 years seen for treatment of asthma at Grady Memorial Hospital, Atlanta, Ga. Eighty children in this study were enrolled in the emergency department and 64 in hospital clinics. Dust from 57 homes, assayed for three indoor allergens (dust mite, cat, and cockroach), revealed similar exposure for asthma and control groups. Sixty-nine percent of the children with asthma had IgE antibodies to dust mite, cockroach, or cat; only 27% of the control subjects were similarly sensitized (p < 0.001). Of 35 children with asthma 21 had both sensitization and significant exposure to the relevant allergen; this was true for only 3 of 22 control subjects (odds ratio, 9.5; p < 0.001). Neither sensitization nor exposure to cat allergen was common in this population. The results show that black children in inner city Atlanta are exposed to high levels of mite and cockroach allergens and that a high proportion of the children with asthma are sensitized to these allergens; the combination of sensitization and exposure is a major risk factor for asthma in this population. PMID- 1447647 TI - Clinical spectrum of chronic interstitial lung disease in children. AB - To describe the clinical spectrum of interstitial lung disease in children, we reviewed our experience with 48 patients during a 12-year period. Most patients initially had typical findings of restrictive lung disease and hypoxemia. Growth failure or pulmonary hypertension or both were found in more than one third. Specific diagnosis, made in 35 patients (70%), most often required invasive studies, particularly open lung biopsy. Although the diagnostic yield from open lung biopsy was high, the diagnosis of many patients remained uncertain. Many different disorders were encountered. The response to corticosteroids, bronchodilators, and chloroquine was inconsistent. Six patients died, five within 1 year after the initial evaluation. The spectrum of pediatric interstitial lung disease includes a large, heterogeneous group of rare disorders associated with high morbidity and mortality rates. PMID- 1447648 TI - Cryptococcal osteomyelitis and cellular immunodeficiency associated with interleukin-2 deficiency. AB - We describe an unusual example of cellular immunodeficiency associated with interleukin-2 deficiency in an otherwise healthy 15-year-old boy who had isolated cryptococcal osteomyelitis of the scapula at 10 years of age. His previous medical history was remarkable only for prolonged, severe varicella infection at 6 years of age. He had persistent moderate lymphopenia, anergy, and absent lymphocyte blastogenic responses to mitogens, antigens, or monoclonal T cell antibodies. Subnormal blastogenic responses were seen after exposure to high concentrations of phorbol esters. Immunoglobulin levels and specific antibodies were normal. The patient has been in good health since treatment of his osteomyelitis. However, his lymphocyte blastogenic responses to mitogens have remained absent during 4 years of observation; investigation of the cause revealed a specific interleukin-2 deficiency resulting from defective generation of interleukin-2 messenger ribonucleic acid. Secretion of interleukin-1 by monocytes was normal, suggesting that the abnormal blastogenic response and interleukin-2 production were due to a problem intrinsic to T lymphocytes. The generation of messenger ribonucleic acid for interleukin-4 was not affected. Interferon-gamma was produced at subnormal levels. The addition of recombinant interleukin-2 restored lymphocyte blastogenic responses and increased the expression of interleukin-2 receptors. The clinical findings and immunologic abnormalities present in this patient differ from other primary and secondary immunodeficiencies associated with interleukin-2 deficiency. Thus our observations in this patient extend the spectrum of immunodeficiencies associated with abnormalities in the production of this important cytokine. PMID- 1447649 TI - Preservation of ovarian function by ovarian transposition performed before pelvic irradiation during childhood. AB - Ovarian transposition in adults has been shown to protect ovarian function in about 60% of cases by reducing ovarian exposure to less than 4 to 7 Gy. We therefore evaluated the effect of ovarian transposition during childhood or adolescence. Eighteen girls had ovarian transposition performed at a mean (+/- SEM) age of 9.4 +/- 1.2 years (range, 1.2 to 16 years). Twelve were prepubertal and six had menstruated at the time of ovarian transposition. The initial abnormalities were Hodgkin disease (5 cases), iliac Ewing sarcoma (3), medulloblastoma (2), ovarian seminoma (1), and vaginal or uterine tumor (7). The irradiation was external in 11 cases and local by vaginal curietherapy in 7 cases. Fifteen girls received chemotherapy. The ovarian transposition was bilateral in 15 patients and unilateral in 3 cases; in the latter the other ovary had been destroyed by the tumor or by abdominal irradiation. Ovaries were placed just below the iliac crest (15 cases) or posterolateral to the uterus (3); thus, the calculated ovarian radiation dose was up to 9.5 Gy. At the time of evaluation (8.6 +/- 0.9 years after ovarian transposition), 16 girls had menstruated and 2 remained amenorrheic because of major lesions of the vagina and uterus caused by the vaginal curietherapy. Basal plasma gonadotropin values were normal. Ovulation was documented in seven cases. Two pregnancies occurred. Complications of ovarian transposition were present in four patients: intestinal occlusion, dyspareunia, functional ovarian cysts, and pelvic adhesions with tubal obstruction. We conclude that ovarian transposition, performed before abdominopelvic irradiation during childhood, can preserve ovarian function. Longer follow-up is required to assess the risk of ovarian dystrophy because of vascular lesions or chemotherapy. PMID- 1447650 TI - Chemotherapy for acute lymphocytic leukemia: cognitive and academic sequelae. AB - Iatrogenic cognitive impairments have been reported for survivors of childhood leukemia after prophylactic central nervous system therapy with craniospinal radiation. To determine whether chemotherapy alone might be a source of central nervous system damage, we assessed in a cross-sectional design the cognitive and academic functioning of 48 children with acute lymphocytic leukemia who were at various stages in their treatment or who had completed treatment. The off-therapy patients who had completed a 3-year course of chemotherapy were more impaired in tasks of higher-order cognitive functioning than were those children whose leukemia had been newly diagnosed and those children whose diagnoses had been 1 year earlier. Off-therapy patients also had concomitant diagnosable learning disabilities in mathematics. We recommend appropriate liaison and special education placements, as well as continued evaluation of cognitive and leaning functioning of children treated for moderate-risk acute lymphocytic leukemia who receive chemotherapy alone. PMID- 1447651 TI - Clinical response of alopecia, trichorrhexis nodosa, and dry, scaly skin to zinc supplementation. AB - Two unrelated patients had dry brittle hair, alopecia, trichorrhexis nodosa, dry scaly skin, pigment dyschromia, short stature, and neurosecretory growth hormone deficiency. By means of the zinc tolerance test, patient 1 was shown to have zinc deficiency, whereas no clear zinc deficiency could be demonstrated in patient 2. In both patients, hair and the skin abnormalities responded to oral zinc therapy. PMID- 1447652 TI - Fatal infantile liver failure associated with mitochondrial DNA depletion. AB - A 3-month-old girl was admitted to the hospital because of hypotonia and frequent vomiting. She had severe metabolic acidosis and her liver function was abnormal. Hepatomegaly and rapidly progressive liver failure developed, and she died at 4 months of age. Two half-siblings from a different mother had died in infancy of an undiagnosed myopathy. The liver was fatty and hepatocytes were filled with large and small lipid droplets. Other tissues were morphologically normal. The respiratory chain enzymes containing subunits encoded by mitochondrial DNA were markedly decreased in liver, partially decreased in muscle, but normal in other tissues. Southern blot analysis showed 90% depletion of mitochondrial DNA in liver, 53% depletion in muscle, and normal amounts in other tissues. This is the second case of fatal infantile liver failure associated with mitochondrial DNA depletion. This pathogenetic mechanism should be considered in infants with multiple respiratory chain defects and variable tissue expression. PMID- 1447654 TI - Thickened feedings as a cause of increased coughing when used as therapy for gastroesophageal reflux in infants. AB - To determine whether thickening of infant formula feedings with rice cereal increases coughing, we studied 25 infants from birth to 6 months of age, referred for evaluation of gastroesophageal reflux. Coughing was blindly quantified after each of a pair of isocaloric meals (one thickened and one unthickened). Coughing was more frequent after thickened feedings than after unthickened feedings. PMID- 1447653 TI - Olfactory performance during childhood. I. Development of an odorant identification test for children. AB - Because there has been no suitable diagnostic instrument for evaluation of olfaction in children, we designed an odorant identification test for that purpose. We screened 40 microencapsulated odorants ("scratch 'n' sniff" cards) by randomly grouping them into 40 overlapping sets of five odorants each. Forty-one children, 4 and 5 years of age, tried to identify each test odorant, selecting their responses from among five photographs depicting the substances in the set of odorants. We used the results to select a subset of five odorants (baby powder, bubble gum, candy cane, fish, and orange). To determine how well these odorants could be identified by normal children, we tested another 134 subjects, 3 1/2 to 13 years of age. For children 3 1/2 years to 5 years 4 months of age, the mean (+/- SEM) percentage of correct responses increased from 66% +/- 8% to 92% +/- 2%. Thereafter the mean percentage of correct responses remained at a plateau of about 90%. The 10th percentile for the percentage of correct responses tended to be higher for girls than for boys throughout childhood. We concluded that this set of five odorants can be correctly identified by most normal children 5 years of age or older. The performances of three older subjects with Kallmann syndrome were all subnormal, but the overall efficacy of the test for evaluating children with olfactory deficits needs to be determined. PMID- 1447655 TI - Pseudomembranous colitis in sickle cell disease responding to exchange transfusion. AB - We report a case of ischemic colitis with pseudomembrane formation in a 6 1/2 year-old boy with sickle cell disease that responded to medical management including exchange transfusion. This case was not associated with Clostridium difficile infection but with an elevation of serum levels of tumor necrosis factor alpha. This rare complication of sickle cell disease has been reported only in adults. PMID- 1447656 TI - Symptomatic hyperammonemia caused by a congenital portosystemic shunt. AB - A child with trisomy 21 had altered mental status and hyperammonemia at presentation and was found to have a congenital portosystemic shunt as a result of a congenital abnormality of the portal venous system. Anomalies of the portal venous system leading to portosystemic shunting, although they are infrequent, should be considered in the differential diagnosis of hyperammonemia. PMID- 1447657 TI - Congenital idiopathic growth hormone deficiency associated with prenatal and early postnatal growth failure. The International Board of the Kabi Pharmacia International Growth Study. AB - To assess the role of growth hormone in fetal and infant growth, we analyzed the pretreatment data on 52 patients with a diagnosis of congenital growth hormone deficiency before 2 years of age, obtained from the Kabi Pharmacia International Growth Study. These infants had reduced birth-length standard deviation scores, an excess of birth weight relative to length, and progressive growth failure. We conclude that congenital growth hormone deficiency may cause impaired growth in utero and early infancy, and that growth hormone plays an important role in perinatal and infantile growth. PMID- 1447658 TI - Serial changes of serum interleukin-6, interleukin-8, and tumor necrosis factor alpha among patients with Kawasaki disease. AB - To determine the role of cytokines in Kawasaki disease, serial measurements of serum cytokine levels were done in 60 patients treated solely with aspirin. Coronary artery aneurysms later developed in 12 of them. The results suggest that elevated serum interleukin-6 and interleukin-8 levels during the first week of illness may be associated with a higher risk of coronary aneurysm formation. PMID- 1447659 TI - Cerebral artery aneurysms in children infected with human immunodeficiency virus. AB - More than 250 children treated at our institution on antiretroviral treatment protocols have been monitored with brain imaging studies. We documented the occurrence and progression of aneurysms of major cerebral arteries in two children with advanced human immunodeficiency virus infection. In both cases these lesions remained clinically silent initially, despite progression to marked dilation. PMID- 1447660 TI - Idiopathic arterial calcification of infancy: prenatal and postnatal effects of therapy in an infant. AB - In an infant with idiopathic arterial calcification of infancy, prenatal diagnosis of arterial calcification was made by ultrasonography and allowed initiation of therapy in utero. Etidronate therapy produced apparent radiographic and ultrasonographic improvement in the degree of vascular calcification but did not prevent the lethal progression of intimal vascular occlusive disease. PMID- 1447661 TI - Arterial thrombosis and protein S deficiency. AB - A previously healthy boy had progressive painful discoloration of the lower extremities and was treated with exchange transfusion and anticoagulation, which were unsuccessful in arresting pedal ischemia; amputation of all of the child's toes was required. Studies of the patient and his parents resulted in a diagnosis of inherited protein S deficiency. PMID- 1447662 TI - Sarcoidosis associated with nephrocalcinosis in young children. AB - Three patients with nonpulmonary sarcoidosis had chronic erythema nodosum within the first 2 years of life. Each subsequently had renal sarcoidosis and nephrocalcinosis; hypercalcemia was documented in each patient and hypercalciuria in two patients. Treatment with prednisone was not uniformly successful in normalizing creatinine clearance. Nephrocalcinosis may be more common than previously reported in patients with sarcoidosis. PMID- 1447663 TI - 3-Methylglutaconic aciduria associated with Pearson syndrome and respiratory chain defects. AB - 3-Methylglutaconic aciduria was detected in four patients with Pearson syndrome, a multitissue disorder with hematologic abnormalities, lactic acidosis resulting from defective oxidative phosphorylation, and deletions in the mitochondrial genome. 3-Methylglutaconic acid may be an additional useful marker for Pearson syndrome and may be a more specific marker than other organic acids identified in this disorder. PMID- 1447664 TI - Obstructive, mixed, and central apnea in the neonate: physiologic correlates. AB - In an attempt to determine physiologic responses to neonatal apnea, we evaluated changes in heart rate and oxygen saturation as measured by pulse oximetry during 2082 episodes of apnea lasting 15 seconds or more in 47 infants less than 34 weeks of gestational age with idiopathic apnea of prematurity. Of these episodes, 832 (39.9%) were central, 1032 (49.6%) were mixed, and 218 (10.5%) were obstructive. Oxygen saturation decreased with increasing duration of apnea regardless of type or treatment, and the decrease in saturation was correlated with preapnea saturation. The baseline heart rate was similar for all apnea types. Infants receiving doxapram had a lower baseline heart rate (137.8 +/- 10.5 beats/min) than did infants receiving no therapy (142.8 +/- 16.6 beats/min) and infants receiving theophylline (149.7 +/- 15.0 beats/min) (p = < 0.001). A heart rate fall to less than 100 beats/min was seen more frequently with central apnea than with mixed or obstructive events, and in infants who were not receiving therapy. Falls in heart rate were significantly less in infants receiving doxapram (27.8% +/- 18.0%) than in infants receiving theophylline (44.5% +/- 19.0%) or no therapy (48.4% +/- 18.3%) (p = < 0.001). The most common heart rate pattern overall was a gradual decrease interrupted by accelerations, whereas an initial heart rate acceleration was the most common pattern in obstructive apnea. We conclude that heart rate response to neonatal apnea is a complex and is dependent on therapy and on type and duration of apnea. PMID- 1447665 TI - Early metabolic effects of sepsis in the preterm infant: lactic acidosis and increased glucose requirement. AB - The effects of sepsis on carbohydrate metabolism were studied in preterm newborn infants (weight > 1.2 kg, appropriate for gestational age) without maternal endocrine problems who were being examined for infection. Plasma glucose, lactate, and insulin concentrations were measured at initial evaluation and then every 8 hours for a total of 48 hours. Blood, urine, and spinal fluid were obtained for culture and counterimmunoelectrophoresis. Dextrose was administered to each patient to maintain glucose levels in the normal range. Dextrose infusion rates were calculated in milligrams per kilogram per minute. Of the 29 infants, 6 had sepsis (positive culture and counterimmunoelectrophoresis results). Infants with sepsis had significant elevations of plasma lactate concentration (p < 0.003) but normal pH. The dextrose infusion rate was also significantly elevated in the infected infants (p < 0.01). No hypoglycemia or hyperglycemia was observed in either group. No significant difference in plasma insulin concentration was observed. We conclude that significant elevations in plasma lactate concentrations and dextrose infusion rate may be early clinical markers of neonatal sepsis in the first 48 hours of life. PMID- 1447666 TI - Increased nosocomial infection in neutropenic low birth weight (2000 grams or less) infants of hypertensive mothers. AB - The neutropenia often seen in infants of hypertensive mothers (IHMs) at < 12 hours of age has been associated with nosocomial infection in the first 18 days of life. To assess maternal hypertension as an independent factor for nosocomial infection, we compared 101 low birth weight (< or = 2.00 kg) IHMs to a concurrent birth weight-matched group of infants of normotensive mothers (INMs). Infants without differential leukocyte counts at < 12 hours of age were excluded, leaving 93 IHMs and 98 INMs. The incidence of neutropenia at < 12 hours among IHMs was not significantly different from that among INMs (42/92 (45%) vs 37/98 (38%)). Nosocomial infection was more frequent in neutropenic IHMs than in neutropenic INMs (12/42 vs 2/37; p = 0.007). Infection in IHMs included omphalitis (2 infants), pneumonia (4), and sepsis with or without meningitis (6); INMs had cellulitis (1) and sepsis (1). The underlying mechanism(s) for this predisposition remains to be elucidated, although limited data suggest that neutropenia may be more severe and prolonged among IHMs. PMID- 1447667 TI - Response of preterm infants to hepatitis B vaccine. AB - Ninety-nine preterm infants with birth weights < 1750 gm had three doses of hepatitis B vaccine. Fifty-seven received the first dose when they weighed > or = 1000 gm (group 1) and 42 when they weighed > or = 2000 gm (group 2). The final seropositive rates and geometric mean titers of group 1 infants (79%, 61 mIU/ml) and group 2 infants (91%, 262 mIU/ml) were less than that of 43 normal term infants (100%, 679 mIU/ml). PMID- 1447668 TI - A fatal neonatal case of medium-chain acyl-coenzyme A dehydrogenase deficiency with homozygous A-->G985 transition. AB - A term neonate became lethargic and hypotonic at 46 hours of age and died 10 hours later despite supportive therapy. Urinary organic acids indicated medium chain acyl-coenzyme A dehydrogenase deficiency, and DNA studies confirmed this disorder. Neonatal symptoms in this enzyme deficiency have rarely been reported, and recent reviews have ignored or discounted this presentation. PMID- 1447669 TI - Effect of age on ibuprofen pharmacokinetics and antipyretic response. AB - The effect of age on ibuprofen pharmacokinetics and antipyretic effect was studied in 49 infants and children aged 3 months to 10.4 years. The relationship of plasma concentration to antipyretic effect was examined in 38 of the children by using an iterative least squares technique that allows estimation of drug concentration with time in a theoretical effect compartment and rate constant for elimination of drug from the effect compartment. There was a delay of 1 to 3 hours between peak ibuprofen plasma concentration and peak temperature decrement. The mean elimination rate constant from the effect compartment was 0.6 hour-1, corresponding to a half-life of drug in the effect compartment of 1.1 hours. The mean slope of the effect compartment concentration versus temperature regression line was -0.242 degrees C/mg per liter. Age did not significantly influence the rate of absorption of ibuprofen, its plasma concentration, its rate of elimination, or the time course of ibuprofen concentration in the effect compartment. However, in younger children the onset of antipyresis was earlier, maximum antipyretic effect was greater, and the area under the curve of the percentage of change in temperature from baseline versus time was greater than in older children. We conclude that the greater relative body surface area in younger children may allow more efficient dissipation of heat in response to antipyretic-induced lowering of the temperature "set point" in the hypothalamus. PMID- 1447670 TI - Pharmacokinetics and pharmacodynamics of bumetanide in neonates treated with extracorporeal membrane oxygenation. AB - Eleven term neonates treated with extracorporeal membrane oxygenation received bumetanide to treat volume overload. All patients had stable renal function, no history of prior diuretic therapy, and no overt evidence of hepatobiliary disease or hypoalbuminemia. Pretreatment creatinine clearance was 35.2 +/- 4.5 ml/min per 1.73 m2 (range, 20.3 to 57.5). Bumetanide, 0.095 +/- 0.003 mg/kg, was administered for 2 minutes into the postmembrane side of the extracorporeal membrane oxygenation circuit. Serial plasma and urine samples were collected for measurement of bumetanide and electrolyte concentrations. Total plasma and renal clearances for bumetanide were 0.63 +/- 0.11 and 0.16 +/- 0.04 ml/min per kilogram, respectively. The steady-state volume of distribution (0.44 +/- 0.03 L/kg) and the elimination half-life (13.2 +/- 3.8 hours) were greater than similar values reported in previous studies of bumetanide disposition in premature and term neonates who were not treated with extracorporeal membrane oxygenation. At observed rates of bumetanide excretion, the diuretic, natriuretic, and kaliuretic responses were linear. Significant diuresis, natriuresis, and kaliuresis were observed, although the duration of these effects was less than expected given the prolonged renal elimination of bumetanide. Nonrenal elimination of bumetanide was variable (47.2% to 96.9%) but higher than expected; this may explain the relatively brief diuretic and kaliuretic response. PMID- 1447671 TI - Treatment of peripheral tissue ischemia with topical nitroglycerin ointment in neonates. AB - Four neonates had resolution of peripheral tissue ischemia after the application of 2% nitroglycerin ointment. A dosage of 4 mm nitroglycerin ointment per kilogram of body weight was applied to two patients with ischemia caused by vasospasm from indwelling radial artery catheterization and to two patients with ischemia resulting from dopamine extravasation. No adverse effects were noted except mild episodes of decreased blood pressure in two of the patients. PMID- 1447672 TI - Tardive dyskinesia associated with use of metoclopramide in a child. AB - Tardive dyskinesia is a chronic, often permanent, movement disorder that has been reported in elderly patients receiving metoclopramide. We describe an 8-year-old boy with tardive dyskinesia that developed when he received metoclopramide as part of therapy for gastroesophageal reflux and erosive esophagitis. PMID- 1447673 TI - Unforgettable patients. PMID- 1447674 TI - Applications of DNA fingerprinting. PMID- 1447675 TI - Lipoprotein profile of children receiving theophylline therapy. PMID- 1447676 TI - Treatment of chronic thrombotic thrombocytopenic purpura. PMID- 1447677 TI - Detrimental effects of hypotonic cromolyn sodium. PMID- 1447678 TI - Neonatal herpes simplex virus infection: mean age at onset. PMID- 1447679 TI - Neurotoxicity of panipenem/betamipron, a new carbapenem, in rabbits: correlation to concentration in central nervous system. AB - The neurotoxic potential of panipenem/betamipron (PAPM/BP), a new carbapenem antibiotic, was compared with that of imipenem/cilastatin (IPM/CS). The drug concentration in cerebrospinal fluid (CSF) at the onset of epileptogenic electroencephalographic (EEG)-activity and the drug distribution into the central nervous system (CNS) were evaluated. Epileptogenic reactions correlated well with drug levels in CSF, but not with drug levels in circulating plasma. The concentration of PAPM in CSF at the onset of epileptogenic EEG-activity was almost twice that of IPM, suggesting that neurotoxic activity of PAPM is about half that of IPM. In addition, in terms of incidence percent for the epileptogenic EEG-activity, PAPM/BP was found to be less toxic than IPM/CS within the dose of 1.0-1.2 g/kg. Concentrations of PAPM in CSF and brain extracellular fluid after PAPM/BP i.v. infusion were comparable with those of IPM after IPM/CS infusion, indicating the similar characteristics of distribution into the CNS for the two antibiotics. From these results of pharmacologic effects and drug distributions, it is suggested that the neurotoxicity of PAPM/BP is less than half that of IPM/CS. PMID- 1447680 TI - Are free radicals involved in Ca(2+)-induced membrane damage of mitochondria? AB - Ca(2+)-Induced membrane damage of energized mitochondria has been proposed to be due to lipid peroxidation induced by Ca2+. To examine this possibility, we studied the effects of the radical scavenger, 3,5-di-tert-butyl-4-hydroxytoluene (BHT), and its derivative, 3,5-di-tert-butyl-4-methoxytoluene (MeO-BHT), on membrane damage of respiring mitochondria induced by Ca2+ in the presence of inorganic phosphate. Both compounds inhibited Ca(2+)-induced damage almost completely at 20 microM, and their effects were identical, although MeO-BHT had no radical scavenging ability. These results indicate that the protective effects of BHT and MeO-BHT are not due to their radical scavenging ability. Thus, free radicals are concluded not to be involved in Ca(2+)-induced membrane damage of mitochondria. PMID- 1447681 TI - Importance of hydrolysis of amino acid moiety in water-soluble prodrugs of disodium cromoglycate for increased oral bioavailability. AB - The relationship between physicochemical properties and oral absorption was investigated in prodrugs for the oral delivery of disodium cromoglycate (DSCG). To improve the lipophilicity of DSCG, various lipophilic moieties were introduced into the twin carboxyl groups. However, this did not lead to improved oral absorption in rabbits because of loss of water solubility, in spite of improved lipophilicity. Water-soluble prodrugs, in which an amino acid was introduced into a hydroxy group by ester linkage in addition to ethyl residues at twin carboxyl groups of DSCG, were synthesized and examined for oral absorption in rabbits and rats. The oral absorption of these prodrugs was affected by the species of amino acids introduced as a water-soluble moiety. Therefore, we examined the relation between the oral absorption of water-soluble prodrugs and the hydrolysis rate of the amino acid moiety. A good linear correlation was obtained between the oral absorption and the hydrolysis rate constant catalyzed by digestive enzymes, trypsin or alpha-chymotrypsin. It was thus concluded that the amino acid moiety of water-soluble prodrugs must be rapidly hydrolyzed to a permeable lipophilic prodrug still possessing the ethyl moiety at twin carboxyl groups in the small intestinal tract for good oral absorption. PMID- 1447682 TI - Percutaneous absorption of pindolol and pharmacokinetic analysis of the plasma concentration. AB - The percutaneous (p.c.) absorption of pindolol, a beta-blocker, through rabbit skin was examined by in vitro and in vivo studies. Additionally, for practical use of the transdermal system (TTS), a trial for sustaining a suitable plasma concentration of pindolol by using a rate-controlling membrane and for describing plasma drug levels after p.c. application by using a simple pharmacokinetic model was tested. As a result, the drug penetrated through rabbit skin in vitro at a zero-order rate. In vivo, the drug was also absorbed through the skin from a gel base with or without enhancers. The gel preparation with Azone (Rp. 2) gave high plasma levels of pindolol. The transdermal system produced with Rp. 2 and a rate controlling membrane (Hipore 4050) provided relatively constant plasma levels for 48 h. The model presented could describe the time course of plasma pindolol concentrations following p.c. application of the systems. PMID- 1447683 TI - Generation of senescent antigen on erythrocytes by partial blocking of SH groups of the membrane proteins. AB - Human erythrocytes treated with diamide (0.2 mM) or N-ethylmaleimide (0.1 mM) at 37 degrees C for 1 h were susceptible to binding of anti-band 3 immunoglobulin G autoantibody and hemoglobin. A definite degree of cell modification appeared to be required for the effective bindings since the cells treated with the reagents above these concentrations were less susceptible. The enhanced binding activities of the cells treated with diamide were abolished on treatment with dithiothreitol. Partial blocking of SH groups of the membrane proteins but not disulfide-mediated protein cross-linking may be essential for the formation of band 3 senescent antigen, which may not be a neo-antigen formed by chemical modification of band 3 but an antigen formed by topological alterations of the molecules in the membrane. PMID- 1447684 TI - Cognitive-experiential self-theory and subjective probability: further evidence for two conceptual systems. AB - Three experiments (N = 1,331) demonstrated that research findings on suspiciousness about coincidences (Miller, Turnbull, & McFarland, 1989) can be accounted for in terms of subjective probability, as predicted by cognitive experiential self-theory (CEST) but in contrast with the norm theory (NT) account offered by Miller et al. (1989). Ss participated in a hypothetical (Experiments 1 and 2) or real (Experiment 3) lottery game in which they chose between 2 bowls offering equivalent probabilities of winning or losing but differing with respect to absolute numbers (e.g., 1 in 10 vs. 10 in 100). Responses across 4 conditions (2 probability levels x 2 outcome types) and across the 3 experiments supported predictions derived from CEST but not those derived from NT. Results are discussed in terms of 2 conceptual systems, rational and experiential, that operate by different rules of inference. PMID- 1447685 TI - Stimulus recognition and the mere exposure effect. AB - A meta-analysis of research on Zajonc's (1968) mere exposure effect indicated that stimuli perceived without awareness produce substantially larger exposure effects than do stimuli that are consciously perceived (Bornstein, 1989a). However, this finding has not been tested directly in the laboratory. Two experiments were conducted comparing the magnitude of the exposure effect produced by 5-ms (i.e., subliminal) stimuli and stimuli presented for longer durations (i.e., 500 ms). In both experiments, 5-ms stimuli produced significantly larger mere exposure effects than did 500-ms stimuli. These results were obtained for polygon (Experiment 1), Welsh figure (Experiment 2), and photograph stimuli (Experiments 1 and 2). Implications of these findings for theoretical models of the mere exposure effect are discussed. PMID- 1447686 TI - Role of meaningful subgroups in explaining differences in perceived variability for in-groups and out-groups. AB - Five aspects of the complexity of the knowledge representation of business and engineering majors were examined to see whether these differed by group membership and whether these differences were related to differences in perceived variability. Significantly more subgroups were generated when describing the in group than the out-group; this difference predicted the relative tendency to see the in-group as more variable, and when controlled for statistically, out-group homogeneity effects were eliminated. Familiarity, redundancy, number of attributes used to describe the group, and the deviance of the subgroups from the larger group generally showed differences for in-group and out-group but did not show consistent evidence of mediation. In a 2nd study, Ss who were asked to sort group members into meaningful subgroups perceived greater variability relative to those who did not perform the sorting task. PMID- 1447687 TI - Mood effects on attitude judgments: independent effects of mood before and after message elaboration. AB - This study investigated the independent effects of induced mood on the encoding of persuasive messages and on the assessment of attitude judgments. In Experiment 1, positive or negative mood was induced either before the encoding of a counterattitudinal message or before the assessment of attitude judgments. When mood was induced before message presentation, Ss in a bad mood were more persuaded by strong than by weak arguments, whereas Ss in a good mood were equally persuaded by strong and by weak arguments. When Ss encoded the message in a neutral mood, however, the advantage of strong over weak arguments was more pronounced when Ss were in a good rather than in a bad mood at the time of attitude assessment. In Experiment 2, Ss exposed to a counterattitudinal message composed of either strong or weak arguments formed either a global evaluation or a detailed representation of the message. Positive, negative, or neutral mood was then induced. Ss in a good mood were most likely and Ss in a negative mood least likely to base their reported attitudes on global evaluations. PMID- 1447688 TI - Attributions and behavior in marital interaction. AB - To examine whether spouses' attributions for events in their marriage are related to their behavior in interaction, spouses were asked to report their marital quality, to make attributions for marital difficulties, and to engage in problem solving discussions. Study 1 demonstrated that spouses' maladaptive attributions were related to less effective problem-solving behaviors, particularly among wives. Study 2 showed that spouses' maladaptive attributions were related to higher rates of negative behavior and, for wives, to increased tendencies to reciprocate negative partner behavior. In both studies attributions and behavior tended to be more strongly related for distressed than nondistressed wives. These results support social-psychological models that posit that attributions are related to behavior and models of marriage and close relationships that assume that maladaptive attributions contribute to conflict behavior and relationship dysfunction. PMID- 1447689 TI - Moderators of the relation between perceived control and adjustment to chronic illness. AB - It was predicted that the relation between perceived control and adjustment to chronic illness would be stronger when (a) perceptions of control were based in reality and (b) the threat was severe. Perceived control was assessed during the hospitalization of 80 first cardiac event patients, and adjustment was assessed during hospitalization and 3-month follow-up. Results indicated that perceptions of vicarious control (perception that other people and things have control) were related to better adjustment only for patients who had undergone invasive procedures by physicians. The relation between control and adjustment was stronger under more severe threat conditions (poor prognosis and rehospitalization). PMID- 1447690 TI - Vulnerability to depressive symptomatology: a prospective test of the diathesis stress and causal mediation components of the hopelessness theory of depression. AB - The diathesis-stress and causal mediation components of the hopelessness theory of depression (Abramson, Metalsky, & Alloy, 1989) were tested using a prospective methodology. Measures of the 3 vulnerability factors posited by the theory (cognitive diatheses about cause, consequences, and self) were completed by 152 Ss at Time (T) 1. Ss completed measures of depressive symptoms, anxious symptoms, and hopelessness at T1 and again at T2, 5 weeks later. Naturally occurring stressors were assessed at T2 (covering the T1-T2 interval). Consistent with the diathesis-stress component, each Cognitive Diathesis x Stress (CD x S) interaction predicted onset of depressive symptoms from T1 to T2. In contrast, the CD x S interactions predicted neither state nor trait anxiety. In addition, 2 of the 3 CD x S interactions (those involving cause and self, but not consequences) were partially mediated by hopelessness. Implications for future work on the hopelessness theory of depression are discussed. PMID- 1447691 TI - Future-event schemas and certainty about the future: automaticity in depressives' future-event predictions. AB - The proposition was tested that depressives make predictions about the future based on a pessimistic future-event schema. Participants varying in depression predicted whether positive and negative events would happen to them (or to an average person) in the future by pressing yes or no at a computer terminal as quickly as possible, either under a concurrent attentional load or under no such load. As hypothesized, depressives predicted more negative events and fewer positive events than did mild depressives or nondepressives and showed greater automaticity in their predictions. That is, the attentional load did not increase depressives' response latencies for either negative or positive events, even though it did so reliably for both mildly depressed and nondepressed individuals. Depressives may thus possess a highly developed future-event schema that operates efficiently in enabling future-event predictions. PMID- 1447692 TI - Natural sample spaces and uncertain belief. AB - This article proposes a novel framework for understanding judgments of probability. Both accurate and inaccurate judgments are conceptualized in terms of the sets of information, or sample spaces, on which they are based. When appropriate sample spaces are easily accessed from memory (e.g., when they correspond to natural cognitive categories), people will make relatively accurate judgments; otherwise, people may substitute more accessible but inappropriate sample spaces and make judgment errors. In 3 experiments, the sample space framework was applied to account for the base rate fallacy. Results showed that (a) people spontaneously access sample spaces that correspond to natural categories, (b) reliance on inappropriate sample spaces produces the base rate fallacy, and (c) highlighting appropriate sample spaces improves the sensitivity of people's judgments to base rates. Discussion extends the framework to explain accuracy and error in other judgment domains. PMID- 1447693 TI - Judgments of genuine, suppressed, and faked facial expressions of pain. AB - The process of discriminating among genuine, suppressed, and faked expressions of pain was examined. Untrained judges estimated the severity of pain being experienced when viewing videotaped facial expressions of chronic pain patients undergoing a painful diagnostic test or dissimulating reactions. Verbal feedback as to whether pain was experienced also was provided, so as to be either consistent or inconsistent with the facial expression. Judges were able to distinguish genuine pain faces from baseline expressions but, relative to genuine pain faces, attributed more pain to faked faces and less pain to suppressed ones. Advance warning of deception did not improve discrimination but led to a more conservative or nonempathic judging style. Verbal feedback increased or decreased judgments, as appropriate, but facial information consistently was assigned greater weight. An augmenting model of the judgment process that attaches considerable importance to the context in which information is provided was supported. PMID- 1447694 TI - Sensation seeking and selective attention: focused and divided attention on a dichotic listening task. AB - Differences in selective attention as a function of sensation seeking, extraversion, neuroticism, and psychoticism were examined in 108 undergraduates using a dichotic listening task. Dependent measures included shadowing performance, reaction times to a secondary light task, target detection, and recall. The results suggested that high sensation seekers have better focused attention than low sensation seekers, and these effects were strongest on the 1st trials of the shadowing tasks. High sensation seekers did not attend differently than low sensation seekers to words related to their interests (sexual, violent, or drug related). Extraversion was associated with greater recall of these kinds of words, although there were no overall differences in selective attention as a function of Eysenck's dimensions. The role of arousal in personality and attention is discussed, particularly in regard to the response of sensation seekers to task novelty. PMID- 1447695 TI - Self-reports of depression and state-trait anxiety: evidence for differential assessment. AB - Several researchers have found anxiety and depression to be indistinguishable in nonclinical samples and have suggested that both constructs may be components of a general psychological distress process. Another possibility is that overlap is due to the psychometric limitations of scales used. A series of exploratory factor analyses were conducted in a nonclinical sample (N = 605) using the Beck Depression Inventory (BDI; Beck, 1978), the State-Trait Anxiety Inventory (STAI; Spielberger, 1983), and the Endler Multidimensional Anxiety Scales (EMAS; Endler, Edwards, & Vitelli, 1991). Both state and trait anxiety and depression could be differentiated with the BDI and the EMAS but not with the STAI. Some theoretical models of negative affectivity or general psychopathology may be premature. PMID- 1447696 TI - Age-related changes in cardiovascular response as a function of a chronic stressor and social support. AB - The effects of aging, chronic stress, and social support on cardiovascular functioning were examined using a cross-sectional design. Thirty-six family caregivers of Alzheimer's disease victims and 34 control Ss performed 2 active coping tasks while continuous noninvasive measures of cardiovascular activity were monitored. Results revealed that caregivers high in social support displayed typical age-related decreases in heart-rate reactivity, whereas caregivers low in social support displayed age-related increases in heart-rate reactivity. Analyses further indicated that only Ss with low social support were characterized by age related increases in systolic blood pressure. These results suggest that social support can moderate age-related changes in cardiovascular functioning, particularly in Ss exposed to a chronic stressor. PMID- 1447697 TI - Interpretive sets, expectancy, fantasy proneness, and dissociation as predictors of hypnotic response. AB - College students with no prior experience of hypnosis were assessed for fantasy proneness and dissociation. In a totally separate context, they were subsequently tested for their interpretations of hypnotic suggestions, hypnotic response expectancies, and hypnotizability. Contrary to Spanos and Gorassini's (1984) hypothesis, strategic enactment of suggested responses was rarely reported, and its endorsement was not correlated with hypnotic responsiveness. Suggestibility was significantly predicted by fantasy proneness and response expectancy, but not by dissociation. A path analysis suggested that the relation between fantasy proneness and hypnotizability was partially mediated by expectancy. PMID- 1447698 TI - Social conflict, social support, and psychological distress: evidence of cross domain buffering effects. AB - A longitudinal study examined the relative and joint effects of perceived social support and social conflict on psychological distress in 228 college students. Women had higher perceived social support from roommates and friends and less conflict with roommates than did men; there were no gender differences in level of conflict with friends or psychological distress. Roommate conflict predicted increases in psychological distress over time; this effect was attenuated by high levels of perceived social support from friends. Friend conflict also predicted increases in psychological distress over time; this effect was attenuated by high levels of perceived social support from roommates. These results show the importance of negative and positive aspects of social experiences to emotional functioning and the importance of compensatory social support for individuals facing social conflicts. PMID- 1447699 TI - Biostability of a non-ether polyurethane. AB - A new type of medical grade polyurethane elastomer, based upon an ether-free macroglycol, has been developed by VASCOR, Inc. Prior research conducted by others has indicated that an ether-free urethane should be inherently immune to biodegradation and environmental stress cracking. Specimens of the experimental polyurethane, along with positive and negative control materials, were formed into tubing, mounted on mandrels, and implanted in rabbits. After being exposed to the in vivo environment for six months, the specimens were explanted and examined with scanning electron microscopy. No indication of degradation was observed in the experimental polymer or negative control specimens, whereas severe microcracking was seen in most of the positive control specimens. PMID- 1447700 TI - Factor analysis in the evaluation of the relationship between bacterial adherence to biomaterials and changes in free energy. AB - The relative surface charge and free energy of forty-one coagulase-negative staphylococci were found to be normally distributed; therefore, they can be considered a homogeneous group under strict statistical criteria. The adherence of these bacteria to eight different biomaterials (seven synthetic and one biologic) was found to be independent of charge and variations in free energy during adhesion. Adherence can be explained as a thermodynamic process (free energy decreased with adherence), except in the case of bovine pericardium in which free energy increases. With these biomaterials, a correlation was found between adherence and bacterial charge. Bacterial adherence and bacterial charge correlate with the surface parameters of the biomaterials. This correlation does not occur when the relationships between parameters are evaluated by means of factors analysis, thus indicating the importance of the statistical method selected for the evaluation of bacterial adherence. PMID- 1447701 TI - Modern wound dressings: a systematic approach to wound healing. AB - The advent of modern wound care management constitutes one of the most innovative applications of medical device technology. The foundation for wound care recent advances has been built upon the developments achieved in polymer technology over the last three decades. New and unique materials have been engineered to provide properties with significant technical and clinical benefits. These new wound care products were made possible by the convergence of three interrelated disciplines: (1) more complete understanding of the underlying principles of dermal wound healing processes, (2) new elastomeric polymers capable of being fabricated into protective dressings, and (3) advances in breathable adhesive technology. The following discussion provides a critical review of the current status of technology and the worldwide opportunities for improved wound management products. Particular attention is focused on the clinical applications of the newer, breathable dressing products, which approximate a temporary synthetic artificial skin. PMID- 1447702 TI - Automated patent search. PMID- 1447703 TI - Nicotine absorption after pulmonary instillation. AB - Levels of nicotine in plasma were determined by gas chromatography in eight mongrel dogs after instillation of 0.5 mg of nicotine in 100 microL of normal saline at three levels of the tracheobronchial tree: the trachea, a subsegmental bronchus of the right middle lobe, and a subpleural location of the right middle lobe ("distal"). An equivalent dose was given intravenously (iv). Peak of nicotine concentrations in plasma were significantly lower after instillation at the trachea (11.5 +/- 4.4 ng/mL) and the subsegmental bronchus (18.2 +/- 5.0 ng/mL) than after an iv dose (30.3 +/- 10.7 ng/mL); p < 0.05 for each comparison. In addition, the peak concentration after instillation at the trachea was significantly lower than that after instillation at the distal site (22.1 +/- 6.2 ng/mL, p < 0.05). Time to peak concentration was significantly longer after tracheal instillation (5.3 +/- 3.0 min) than after subsegmental instillation (2.0 +/- 0.0 min) or iv infusion (2.0 +/- 0.0 min); p < 0.05 for each comparison. Total drug absorbed, half-life, and clearance were equivalent from all four sites. This study demonstrated that quantitative absorption of nicotine from the described lung sites is equivalent to that after an iv dose, with slower absorption and lower peak concentrations from the tracheal site. PMID- 1447704 TI - Synthesis and cytotoxic evaluation of some 6-arylidene-2-(alpha-hydroxyamino alpha-arylmethyl)cyclohexanone oximes and related compounds. AB - Reaction of 2,6-bis-(phenylmethylene)cyclohexanone (1) with a 4-molar excess of hydroxylamine hydrochloride and sodium acetate to produce the corresponding oxime 2 gave rise to 2-(alpha-hydroxyamino-alpha-phenylmethyl)-6 phenylmethylenecyclohexan one oxime (5a), whose structure was deduced from high resolution proton nuclear magnetic resonance spectroscopy and confirmed by X-ray analysis. Compound 2 was eventually prepared from 1 with hydroxylamine per se and not with a mixture of hydroxylamine hydrochloride and sodium acetate. Ten analogues of 5a, namely 5b-5k, were prepared and evaluated for cytotoxicity. Six of the 11 compounds in series 5, as well as 1, showed activity in the 240-950 microM range against murine mammary EMT6 cells. Series 5 was also examined for cytotoxicity in an in vitro screen conducted by the National Cancer Institute with approximately 54 cell lines, and four compounds demonstrated selective toxicity toward various groups of tumors. PMID- 1447705 TI - Radioimmunoassays for a new angiotensin-converting enzyme inhibitor, zabicipril, and its active metabolite, zabiciprilat, in human plasma. AB - Zabicipril (Z), a new angiotensin-converting-enzyme inhibitor under development, is a prodrug that has to be deesterified in vivo to the active metabolite, zabiciprilat (ZT), to reach its antihypertensive pharmacological properties. Two radioimmunoassays have been developed for the measurement of both Z and ZT in human plasma. Anti-Z and anti-ZT antibodies were raised in rabbits against their respective lysine analogues conjugated to bovine serum albumin. [3H]Z and [3H]ZT were used as radioligands for the prodrug (Z) and the drug (ZT), respectively. Studies on anti-Z antiserum specificity showed no significant cross-reactivity (< 0.1%) with the active metabolite (ZT); similarly, Z is poorly recognized (0.5%) by the anti-ZT antiserum. Both antisera showed little cross-reaction (2%) with glucuronide metabolites. The sensitivities of the assays were 1 and 0.2 ng/mL for Z and ZT, respectively. Interassay coefficients of variation ranged from 9 to 12% for Z at 2-50 ng/mL and from 8 to 13% for ZT at 0.5-5 ng/mL. These assays were used to investigate the pharmacokinetic profile of both Z and its pharmacologically active metabolite ZT after intravenous infusion of Z in human volunteers. PMID- 1447706 TI - Disposition of a new diacid angiotensin-converting enzyme inhibitor after intravenous administration of drug or prodrug to monkeys and dogs. AB - The disposition of [4S-[4 alpha,7 alpha,(R*),12b beta]]-7- [S-(1-carboxy-3 phenylpropyl)amino]-1,2,3,4,6,7,8,12b-octahydro-6- oxo- pyrido[2,1 a][2]benzazepine-4-carboxylic acid (MDL 27,088), a new a new angiotensin-covering enzyme inhibitor, was studied in cynomolgus monkeys and beagle dogs given intravenous (iv) doses of MDL 27,088 or its prodrug, MDL 27,210. Although in both species iv-administered MDL 27,210 was extensively (> 99.9%) metabolized and excreted in the urine and feces as MDL 27,088, the disposition of MDL 27,088 appeared to be significantly influenced by its mode of administration. For example, the mean terminal half-life of MDL 27,088 in plasma was longer when MDL 27,088 was given as its prodrug (3.65 and 2.23 h in monkeys and dogs, respectively) than when it was administered directly (0.84 and 1.05 h in monkeys and dogs, respectively). The renal excretion of MDL 27,088 also increased (from 33 to 73% of the dose in monkeys and from 9 to 17% of the dose in dogs) when MDL 27,088 was administered directly versus when it was given as its prodrug. These and other results of this study suggest that the disposition of MDL 27,088 can be significantly altered by iv administration of its prodrug form. Such changes in disposition also suggest that iv administration of prodrug may influence the pharmacological activity of MDL 27,088. PMID- 1447707 TI - A semiempirical computational investigation of the antipsoriatic drug anthralin. AB - A series of computational studies was carried out, by using the highly successful Austin Model 1 (AM1) semiempirical method, to illuminate more completely the fundamental, molecular-level forces that affect the function and utility of the antipsoriatic drug anthralin. First, examination of the keto-enol tautomeric equilibrium by AM1 showed that the keto tautomer of the drug is 9.5 kcal/mol more stable than the enol form. Strong electrostatic forces involving the hydrogens on the hydroxy groups (a partial charge of +0.25 in both forms) and the keto oxygen (a partial charge of -0.40) apparently overcome the effects of the increased aromatic stabilization present in the enol form. Second, AM1 was applied to the degradation products of anthralin, 1,8-dihydroxy-9,10-anthraquinone, 1,8,1',8' tetrahydroxy-10,10'-dianthrone, and a further oxidized form of the dimer. These molecules have been implicated in some of the unpleasant side effects of anthralin. Third, AM1 was used to predict the preferred site of ionization of anthralin. PMID- 1447708 TI - Synthesis and characterization of quaternary ammonium-linked glucuronide metabolites of drugs with an aliphatic tertiary amine group. AB - A synthetic approach was developed to make the quaternary ammonium-linked glucuronide metabolites of compounds with an aliphatic tertiary amine group. The key step involved quaternization of the compound with methyl (2,3,4-tri-O-acetyl alpha-D-glucopyranosyl bromide)uronate and sodium bicarbonate in a two-phase system of water and an organic solvent. The synthetic approach successfully yielded quaternary ammonium-linked glucuronides of 20 drugs and two of their phase I metabolites. The drugs were from various pharmacological classes: H1 antihistamines, antipsychotic agents, and tricyclic antidepressants. Physical data such as HPLC retention times, and diagnostic fast-atom bombardment mass spectra and 1H NMR spectra were obtained. These should aid in the characterization of compounds in samples isolated from biological media. PMID- 1447709 TI - Synthesis of Mannich bases of arylidenepyridazinones as analgesic agents. AB - A series of 5-arylidenepyridazin-3-ones substituted in the 2-position by an arylpiperazinoalkyl moiety (2-16) was synthesized and evaluated for analgesic activity. In the phenylbenzoquinone-induced writhing test, Mannich bases 2-14 were the most active compounds (6.1 < or = ED50 < or = 43.0 mg/kg, orally; ED50 is the half-maximal effective dose). Pyridazinones 8 and 9, with a 3 chlorophenylpiperazinomethyl substituent, also exhibited significant anti inflammatory and antipyretic effects. The activities in the phenylbenzoquinone induced writhing test were subjected to a Hansch analysis, and a significant correlation with lipophilicity and Hammett's constants was obtained. PMID- 1447710 TI - Stability of batanopride hydrochloride in aqueous solutions. AB - The degradation of batanopride hydrochloride, an investigational antiemetic drug, was studied in aqueous buffer solutions (pH 2-10; ionic strength, 0.5; 56 degrees C) in an attempt to improve drug stability for parenteral administration. Degradation occurs by two different mechanisms depending on the pH of the solution. In acidic media (pH 2-6), the predominant reaction was intramolecular cyclization followed by dehydration to form a 2,3-dimethylbenzofuran. There was no kinetic or analytical (high-performance liquid chromatography) evidence for the formation of an intermediate; therefore, the rate of dehydration must have been very rapid compared with the rate of cyclization. In alkaline media (pH 8 10), the primary route of degradation was cleavage of the C-O alkyl ether bond. In the intermediate pH range (pH 6-8), both reactions contributed to the overall degradation. Both degradation reactions followed apparent first-order kinetics. The pH-rate profile suggests that batanopride hydrochloride attains its optimal stability at pH 4.5-5.5. Citrate buffer was catalytic at pH 3 and 5, and phosphate buffer was catalytic at pH 8. No catalytic effect was observed for the borate buffer at pH 9-10. PMID- 1447711 TI - Pharmacological studies on quaternized 4(3H)-quinazolinones. AB - Locomotor activity-inhibiting, anticonvulsant, muscle relaxant, analgesic, and antimicrobial properties of 2-methyl-3-pyridinium-acetylamino-4(3H)-quinazolinone chloride (1), 2-methyl-3-(4-methylpyridinium)acetylamino-4(3H)-quinazolinone chloride (2), 2-methyl-3-(4-ethylpyridinium)acetylamino-4(3H)-quinazolinone chloride (3), 2-methyl-3-(3-carboxamidopyridinium)acetylamino-4(3H)-quinazolinon e chloride (4), and 2-methyl-3-(4-carboxamidopyridinium)-acetylamino-4(3H)- quinazolinone chloride (5) were investigated. The locomotor activity-inhibiting properties and anticonvulsant activity of 2 were almost equal to those of methaqualone. The analgesic activities of 2 and 3 in the hot-plate test were equal to that of aspirin, whereas in the Koster test, the analgesic activity of 2 was higher. The compounds did not exhibit antimicrobial or muscle relaxant properties. Most active compounds had higher lipophilicity values than those of inactive compounds. PMID- 1447712 TI - Stimulation of healing by free radical scavengers of ischemia-induced acute gastric mucosal injury in the rat. AB - Allopurinol and dimethyl sulfoxide (DMSO; 1 mL of 1, 2, or 5% by gavage daily) were used to examine the influence of scavenging oxygen-derived free radicals on the healing of reserpine- (5 mg/kg, intraperitoneal) and 5-hydroxytryptamine- (50 mg/kg, intraperitoneal) induced acute ischemic injury of the rat gastric mucosa. Allopurinol and DMSO demonstrated a time- but not dose-dependent power to stimulate healing of this injury. The magnitude of injury produced by reserpine or 5-hydroxytryptamine (serotonin) followed by gavage with allopurinol or DMSO was significantly (p < 0.01) less after day 4 than that after day 3 of this gavage, and the magnitude after day 3 was itself significantly (reserpine, p < 0.001; 5-hydroxytryptamine, p < 0.01) less than that after day 2 of the same gavage. The actions of allopurinol and DMSO were not associated with any significant influence on H+ output. These results suggest that oxygen-derived free radicals are detrimental to the integrity of the rat gastric mucosa and that scavenging them stimulates healing of the ischemia-induced injury of the mentioned mucosa. PMID- 1447713 TI - In vitro protein binding of propafenone and 5-hydroxypropafenone in serum, in solutions of isolated serum proteins, and to red blood cells. AB - The binding of propafenone (PF) and 5-hydroxypropafenone (5-OH-PF) in serum and in solutions of isolated serum proteins was examined by equilibrium dialysis. Both PF and 5-OH-PF displayed pH-dependent binding in serum and in a solution of alpha-1-acid glycoprotein (AAG). PF displayed extensive binding to AAG (i.e., free fraction of 0.08 +/- 0.02), whereas the binding of 5-OH-PF to AAG was moderate (i.e., free fraction of 0.54 +/- 0.10). The removal of lipoproteins from serum did not alter the free fraction of PF but significantly increased the free fraction of 5-OH-PF compared with that in intact serum. Both PF and 5-OH-PF displayed concentration-dependent binding in a 19.3-mumol AAG solution. Concentration-independent binding was apparent in solutions of human serum albumin, high-density lipoproteins, low-density lipoproteins, and very low density lipoproteins over the PF and 5-OH-PF concentration ranges examined. By use of previously determined binding parameters (affinities and capacities), the binding model of PF provided an estimate of the free fraction in serum that was similar to the observed free fraction, although the free fraction of 5-OH-PF was overestimated. The distribution of PF and 5-OH-PF into red blood cells was extensive when buffer was used as the supernatant; however, when serum was used as supernatant, the amounts of PF and 5-OH-PF that were distributed into red blood cells decreased substantially. PF and 5-OH-PF interacted with all of the proteins examined. PMID- 1447714 TI - Bulk organic solvent-water systems as a possible model to predict alkyl p aminobenzoate partitioning in liposomes. AB - This study compares the bilayer-water distribution coefficients of a homologous series of n-alkyl p-aminobenzoates in liposomes with their respective distribution coefficients in octanol-water, oleyl alcohol-water, and hexane-water systems. The data indicate that the bilayer-water distribution coefficient is quite sensitive to changes in solute structure and to the structural organization of the bilayer and that octanol, oleyl alcohol, and hexane are able to reflect the partitioning changes that occur in the liposomal bilayer with respect to increasing the alkyl chain length of n-alkyl p-aminobenzoates. For this particular homologous series, the hexane-water system tended to underestimate the bilayer-water distribution coefficients, whereas octanol-water and oleyl alcohol water systems overestimated solute partitioning into the bilayer. The similarity of the lipid environment, with respect to solute partitioning, in the organic solvent system and that in liposomes can be ascertained by using the Collander relationship. PMID- 1447715 TI - Gamma-pyrone compounds. II: Synthesis and antiplatelet effects of tetraoxygenated xanthones. AB - Norathyriol and its analogues, 1,3,5,6-, 3,4,5,6-, 3,4,6,7- and 2,3,6,7 tetrahydroxyxanthone, were synthesized from benzophenone precursors by Friedel Crafts acylation and subsequent base-catalyzed cyclization to eliminate methanol. Both 3,4,6,7- and 2,3,6,7-tetrahydroxyxanthone tetraacetate showed potent anti platelet aggregation effects on arachidonic acid-induced platelet aggregation. 3,4,6,7-Tetrahydroxyxanthone tetraacetate and 1,3,5,6-tetrahydroxyxanthone showed potent and significant anti-platelet aggregation effects on collagen-induced platelet aggregation. PMID- 1447716 TI - Pharmacokinetic concepts in assessing intake of pentachlorophenol by rats after exposure through drinking water. AB - The objective of this study was to predict concentrations of a toxicant in plasma after exposure to the toxicant through drinking water using basic pharmacokinetic principles. As an example, we studied pentachlorophenol (PCP), a widely used wood preservative of public health concern as an environmental pollutant. We added PCP to the drinking water (30 micrograms/mL) of five rats for 3 days. Blood was sampled, and water consumption was monitored every 12 h on the days 1 and 2 and every 3 h on day 3. After a 4-day washout, a PCP dose of 2.5 mg/kg was given intravenously, and blood was withdrawn at selected times for 2 days. PCP concentrations in plasma were measured by capillary gas chromatography. A one compartment model with zero-order input and kinetic parameters (clearance, volume of distribution, and bioavailability) estimated after intravenous administration adequately predicted PCP concentrations in plasma during exposure to PCP. The average steady-state concentration (Css), which reflects the overall exposure, was predicted using the clearance (CL) concept [i.e., Css = (bioavailability.rate of intake)/CL] and compared with the observed value. The data for PCP demonstrate the potential utility of CL and other kinetic concepts in assessing exposure to a toxicant in drinking water, food, or air. PMID- 1447717 TI - Enhanced rectal absorption and reduced local irritation of the anti-inflammatory drug ethyl 4-biphenylylacetate in rats by complexation with water-soluble beta cyclodextrin derivatives and formulation as oleaginous suppository. AB - To improve the rectal delivery of ethyl 4-biphenylylacetate (EBA), a prodrug of the anti-inflammatory drug 4-biphenylylacetic acid (BPAA), the use of highly water-soluble 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and heptakis(2,6-di O-methyl)-beta-cyclodextrin (DM-beta-CyD) was investigated and compared with the use of the parent beta-cyclodextrin (beta-CyD). Among the three beta-CyDs, HP beta-CyD was best at improving the rectal bioavailability of EBA in rats after single and multiple administrations of oleaginous suppositories (Witepsol H-5) containing the complexes. To gain insight into the enhancing effect of beta-CyDs, the absorption behaviors of EBA (observed by monitoring BPAA as an active metabolite of EBA) and beta-CyDs themselves were examined in vitro, in situ, and in vivo. The in situ recirculation study revealed that the complexed form of EBA was less absorbable from the rectal lumen in the solution state, but this disadvantageous effect of beta-CyDs was compensated in part by the inhibition of the bioconversion of EBA to BPAA. When beta-CyDs were coadministered with EBA in vivo, however, rather high amounts of HP-beta-CyD (approximately 26% of dose) and DM-beta-CyD (approximately 21% of dose), compared with beta-CyD (approximately 5% of dose), were absorbed from the rat rectum. Thus, the enhancement of rectal absorption of EBA in vivo can be explained by the facts that the hydrophilic beta CyDs increased the release rate of EBA from the vehicle and stabilized EBA in the rectal lumen and that the drug was partly absorbed in the form of the complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447718 TI - Synthesis and antimicrobial properties of 2H-pyran-3(6H)-one derivatives and related compounds. AB - The synthesis of several derivatives of 2H-pyran-3(6H)-ones and their Michael adducts is described. Phenylthio, benzenesulfonyl, p-acetylaminobenzenesulfonyl, and p-bromophenyl substituents are beneficial for activity against gram-positive bacteria. 2-[4-(Phenylthio)phenyl]-2-methyl-6-methoxy-2H-pyran-3(6H)-one (8a) showed a minimum inhibitory concentration of 1.56 micrograms/mL against Staphylococcus aureus ATCC 2593, and 2-[4-(phenylthio)phenyl]-2-methyl-6-[(p nitrobenzoyl)oxy]-2H-pyran-3 (6H)-one (9) showed a minimum inhibitory concentration of 0.75 microgram/mL against Streptococcus sp. C203M. In general, derivatives of 6-hydroxy-2H-pyran-3(6H)-ones with substituents at C-2 and C-6 showed significant activity against gram-positive bacteria. More specifically, the bulkier the C-2 substituent, the greater the antibacterial activity. Michael adducts of thiols (13) showed activity, which may be due to a retro-Michael reaction. In conclusion, the alpha,beta-enone system is essential for the activity of 6-hydroxy-2H-pyran-3(6H)-ones, and the size and nature of substituents at C-2 are associated with antimicrobial activity. PMID- 1447719 TI - Effects of exposure to standard- and nicotine-reduced-cigarette smoke on pharmacokinetics of theophylline and cimetidine in rats. AB - Influences of exposure to standard- (containing nicotine and tar) and nicotine reduced-cigarette smoke on the pharmacokinetics of theophylline (20 mg/kg, per os) and cimetidine (50 mg/kg, per os) were investigated in rats. Animals were exposed to standard- or nicotine-reduced-cigarette smoke for 8 min with a "smoking machine". In control rats, theophylline concentrations in plasma increased rapidly, peaked 2 h later, and then decreased gradually. Concentrations of theophylline in plasma of rats exposed to standard- and nicotine-reduced cigarette smoke were suppressed in comparison with that of control rats, and the suppressive effect of nicotine-reduced-cigarette smoke was weaker than that of standard-cigarette smoke. The suppression of theophylline concentrations in plasma induced by exposure to cigarette smoke may be due to nicotine and other constituents of the cigarette smoke, even if the effects are slight. For cimetidine, no difference was found between drug concentration in plasma of rats exposed to nicotine-reduced-cigarette smoke and that of control rats; however, the drug concentration in plasma of rats exposed to standard-cigarette smoke was markedly suppressed. These results suggest that the suppression of cimetidine concentrations in plasma may be due solely to nicotine in cigarette smoke. PMID- 1447720 TI - Time-dependent distribution volume and kinetics of the pharmacodynamic effector site. PMID- 1447721 TI - Hydrotalcites as potential adsorbents of intestinal phosphate. PMID- 1447722 TI - An internal current source yields immunity of electrosensory information processing to unusually strong jamming in electric fish. AB - The electric organ of a fish represents an internal current source, and the largely isopotential nature of the body interior warrants that the current associated with the fish's electric organ discharges (EODs) recruits all electroreceptors on the fish's body surface evenly. Currents associated with the EODs of a neighbor, however, will not penetrate all portions of the fish's body surface equally and will barely affect regions where the neighbor's current flows tangentially to the skin surface. The computational mechanisms of the jamming avoidance response (JAR) in Eigenmannia exploit the uneven effects of a neighbor's EOD current to calculate the correct frequency difference between the two interfering EOD signals even if the amplitude of a neighbor's signal surpasses that of the fish's own signal by orders of magnitude. The particular geometry of the fish's own EOD current thus yields some immunity against the potentially confusing effects of unusually strong interfering EOD currents of neighbors. PMID- 1447723 TI - Testicular masculinization of vocal behavior in juvenile female Xenopus laevis reveals sensitive periods for song duration, rate, and frequency spectra. AB - In Xenopus laevis, adult males but not females produce courtship songs comprised of rapid trills. Two experiments were conducted to determine whether male-typical singing could be induced in females. At 6 different juvenile stages, male and female frogs were gonadectomized and implanted with testes, grown to sexual maturity, and tested for vocal behavior. All frogs with functional testicular implants sang; females sang as much as males. The frequency spectra of the clicks within trills were fully masculinized in females implanted at PM0, PM1, and PM2. There were deficiencies in song quality in females implanted late in juvenile life. Females receiving testis implants at PM3, PM4, and PM5 did not produce clicks with masculine spectral qualities. In a concurrent experiment, adult males and females were gonadectomized and implanted with testes or silicone tubes containing testosterone propionate. When tested for vocal behavior 10 to 15 months after implantation, 8/10 androgen-treated males, 3/12 androgen-treated females, 5/5 testes-implanted males, and 2/4 testes-implanted females sang. The females that did sing spent much less time singing than males. The click rates of females were uniformly slower than males and no female produced clicks with a masculine frequency spectrum. Thus, testicular secretions can induce male-typical singing in females until late in juvenile development. However, females exhibit a progressive decline in vocal potential with increasing age, culminating in an almost complete loss of singing ability by adulthood. PMID- 1447724 TI - Cone photopigments in nocturnal and diurnal procyonids. AB - Procyonids are small, New World carnivores distributed among some 6 genera. Electroretinogram (ERG) flicker photometry was used to measure the spectra of the cone photopigments for members of two nocturnal species, the raccoon (Procyon lotor) and the kinkajou (Potos flavus), and a diurnal species, the coati (Nasua nasua). Each of the 3 has a class of cone photopigment with maximum sensitivity in the middle to long wavelengths. The spectral positioning of this cone is different for the three. Whereas the raccoon and kinkajou are monochromatic, the diurnal coati is a dichromat having an additional class of cone photopigment with peak sensitivity close to 433 nm. PMID- 1447725 TI - Water-flow sensitive pedal neurons in Tritonia: role in rheotaxis. AB - We have identified 13 pairs of neurons in the pedal ganglia of the marine nudibranch slug Tritonia diomedea that responded tonically and/or phasically to water-flow directed at the rhinophore sheaths and oral veil tips. Most of the neurons responded equally to inputs from either side of the body, but 6 pairs responded with greater intensity to ipsilateral water-flow stimuli. When stimulated intracellularly in a semi-intact, whole-animal preparation, 4 of these 6 pairs of neurons caused ipsilateral movements that may turn the animal towards that side. These observations suggest a role for these current-sensitive neurons in the previously described orientation to water-currents in Tritonia diomedea. PMID- 1447726 TI - Acoustic modulation of neural activity in the preoptic area and ventral hypothalamus of the green treefrog (Hyla cinerea). AB - Responses of neurons in the preoptic area and ventral hypothalamus to conspecific mating calls or white noise bursts were examined in male green treefrogs (Hyla cinerea) during different seasons. In the winter, 34.3% of preoptic neurons and 46.7% of ventral hypothalamic cells demonstrated significant changes in activity level during presentation of a conspecific mating call. In contrast, only 13.3% of preoptic units and 16.7% of ventral hypothalamic cells responded to the white noise. The percentage of preoptic and hypothalamic units responding to the advertisement call did not differ significantly during the summer breeding season. Type I units exhibited a dramatic increase in activity during acoustic stimulation followed by a rapid return to baseline activity levels after stimulus offset. Type II cells showed a robust activity increase during stimulation, but maintained an intermediate activity level after stimulus offset. In the preoptic area, a third response type exhibited suppressed activity during acoustic stimulation. Although seasonal condition did not alter the percentage of acoustically responsive units within either nucleus, the proportion of Type I units in the ventral hypothalamus was greatest during the summer. PMID- 1447727 TI - Word-finding abilities of three types of aphasic subjects. AB - Word-finding difficulties are often observed among different types of aphasic patients. This investigation analyzed the word-finding abilities of 30 aphasic subjects (10 Broca's, 10 Wernicke's, and 10 anomic). Forty nouns counterbalanced according to word length and frequency of occurrence in English language usage were used as stimuli and presented through four modalities (oral expression, writing, auditory comprehension, and reading comprehension). It was expected that patterns of word finding abilities would help in the classification of the different types of aphasia. In addition, long words and less frequently occurring words in English language usage should prove more difficult in word-finding ability, regardless of modality. The results of this study found long words and less frequent words were more difficult for aphasic subjects. Among the modalities, long words were significantly harder than short words for the writing modality only. It was also found that semantic errors were the most common errors for all types of aphasic subjects. Broca's subjects produced significantly more no response errors in oral expression; Wernicke's subjects produced significantly more semantic and phonemic errors in reading comprehension; and, Wernicke's subjects produced significantly more unrelated errors in both oral expression and reading comprehension. Clinical implications were also discussed. PMID- 1447728 TI - Naming disorders and semantic representations. AB - The status of semantic conceptual structures in aphasia was investigated with relation to naming disorders in spontaneous and constrained speech production. A battery of six tasks was administered to 25 control subjects and 25 aphasics: spontaneous speech production (from which the percentage of nouns was calculated), confrontation naming, understanding class relationships (verbal and pictorial), and understanding thematic relationships (verbal and pictorial). Results indicated the important role of taxonomic abilities for naming, while other conceptual structures (i.e., thematic relations) do not seem to play any important role in the process of naming. These results are discussed in terms of the internal organization of semantic information. PMID- 1447729 TI - Acoustic analysis in the differentiation of Parkinson's disease and major depression. AB - In its early stages, Parkinson's disease (P.D.) may be difficult to distinguish from major depression (M.D.) leading to inappropriate management. Both illnesses are characterized by psychomotor retardation. The neurovegetative symptoms used to diagnose M.D. are not specific and in P.D. may be due to the physical illness itself. Currently, differentiation of the two disorders relies on subjective clinical observation. Improved diagnostic accuracy based on more objective data is needed. To this end, this study used computerized acoustic analysis to contrast speech patterns in P.D. and M.D. The sample consisted of 30 P.D. patients without depression or dementia, 30 patients with uncomplicated M.D., and 31 normal controls, each 60 years of age or over. Of the acoustic variables studied, M.D. patients had significantly reduced rates of speech compared with P.D. patients. The data suggest that this temporal measure of speech may be useful in the differentiation of P.D. and M.D. PMID- 1447730 TI - Novel non-cross resistant diaminoanthraquinones as potential chemotherapeutic agents. AB - A novel series of diaminoanthraquinones was discovered initially as protein kinase C inhibitors with IC50s in the 50-100 microM range. They exhibited potent tumor cell growth inhibitory activity in vitro without cross resistance to adriamycin. Further evaluation of two of the most active compounds NSC 639365 (3) and NSC 639366 (4) in human tumor cloning assay showed potent cytocidal activity. The results suggest therapeutical potentials against human tumors. PMID- 1447731 TI - Synthesis and evaluation of novel spermidine derivatives as targeted cancer chemotherapeutic agents. AB - The utility of the spermidine moiety as the homing device for the selective delivery of chemotherapeutic and diagnostic agents into cancer cells was explored. Two spermidine analogs containing a cytotoxic agent were synthesized, N [3,4-bis(benzyloxy)phenethyl]-N alpha-(3-amino-propyl)-L-ornithinamide trihydrochloride, 1a and N-[4-]bis(2-chloroethyl)amino]phenethyl]-N alpha-(3 aminopropyl)-L- ornithinamide tetrahydrochloride, 1b. These compounds were prepared from the fully protected spermidine molecule with a carboxyl group side chain, 8. The ability of the polyamine cytotoxic agents to inhibit B16-BL6 melanoma cell growth in culture was examined. The effects of pretreatment with DFMO on the activity of the synthesized compounds was also studied. The IC50 values of compounds 1a and 1b were on the same order of magnitude as the control compounds, N-acetyldopamine and chlorambucil, respectively. The inhibitory activities of compounds 1a and 1b were not enhanced by pretreatment with DFMO, suggesting that depletion of intracellular polyamines did not enhance the activity of these compounds. PMID- 1447732 TI - Cysteine protease inhibition by azapeptide esters. AB - Papain, a prototype cysteine protease, was inhibited in a time-dependent manner by azapeptide esters designed to deliver an azaglycine group to the active-site thiol. For example, the rate of inhibition was 18 M-1s-1 for Ac-L-PheAglyOiBu (2) and > 11,000 M-1s-1 for Ac-L-PheAglyOPh (7). The rate of inhibition was slowed in the presence of substrate, and there was no reactivation of the inhibited enzyme after dialysis and incubation in the assay buffer. The inhibited enzyme was completely reactivated after the addition of valine methyl ester. The inhibited form of the enzyme is presumed to be acylated on the active-site thiol. An azaalanine-based peptide inhibited papain much more slowly. Azapeptide alkyl esters are unreactive with serine proteases; therefore, these inhibitors are selective for cysteine proteases. PMID- 1447733 TI - Design and synthesis of novel FKBP inhibitors. AB - Small molecule FKBP inhibitors were prepared with inhibitory activity ranging from micromolar to nanomolar. The design of these inhibitors derives from a structural analysis of the substrates for FKBP and cyclophilin. As a consequence of this analysis two key observations were made, namely: (1) amino ketone moieties are suitable as FKBP recognition elements at the P1-P1' site and (2) the P3'-P4' site will accept a trans-olefin as a suitable mimetic of a peptide moiety. The preparation of these non-peptide inhibitors is readily accomplished by a protocol which includes the synthesis of chiral propargylic amines and their subsequent conversion into vinyl zirconium reagents. PMID- 1447734 TI - Effect of conformational mobility and hydrogen-bonding interactions on the selectivity of some guanidinoaryl-substituted mechanism-based inhibitors of trypsin-like serine proteases. AB - Previously, we have reported that some guanidino-substituted alpha- and beta-aryl enol lactones I and II behaved as selective, mechanism-based inhibitors of some trypsin-like proteases (Rai, R.; Katzenellenbogen, J.A. J. Med. Chem., submitted). In this study, we describe the synthesis and kinetic evaluation of some related, guanidino-substituted enol lactones having greater conformational mobility and affording additional hydrogen-bonding sites at the active site. The alpha-aryl-substituted lactones 1 and 2, which have greater conformational mobility in the guanidinoaryl linkage than I, selectively inhibited the trypsin like enzymes, and they were relatively poor inactivators of alpha-chymotrypsin and human neutrophil elastase (HNE). The iodo enol lactone 2 permanently inactivated trypsin, urokinase, tissue plasminogen activator, and plasmin, showing exceptionally high specificity in its interaction with trypsin and urokinase. The selectivity pattern exhibited by the closely related, conformationally less mobile alpha-aryl-substituted iodo lactone Ib, which was previously shown to be a selective suicide substrate of urokinase and plasmin, provides an interesting comparison. The alpha-benzamido-substituted lactones 3 and 4, which afford an additional site for active-site hydrogen bonding, were found to be very potent alternate substrate inhibitors of trypsin and urokinase. In addition, the iodo lactone 4 permanently inactivated alpha-chymotrypsin. The importance of secondary interactions in increasing the specificities in the case of alpha-chymotrypsin is discussed. PMID- 1447735 TI - Synthesis and biological evaluation of conformationally restricted 2-(1 pyrrolidinyl)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methylethylenediam ines as sigma receptor ligands. 1. Pyrrolidine, piperidine, homopiperidine, and tetrahydroisoquinoline classes. AB - The synthesis and sigma receptor affinity of a series of conformationally restricted derivatives of 2-(1-pyrrolidinyl)-N-[2-(3,4-dichlorophenyl)ethyl]-N methylethylenedi amine (1) is described. The pyrrolidinyl (or N,N dialkyl),ethylenediamine,N-alkyl, and phenylethyl portions of this sigma receptor pharmacophore were restricted by its incorporation into 1,2-cyclohexanediamine-, pyrrolidine-, piperidine-, homopiperidine-, and tetrahydroisoquinoline-containing ligands. The sigma receptor binding affinities of these compounds were determined using [3H](+)-pentazocine in guinea pig brain homogenates. The synthesis of all but one class was achieved by acylation and alane reduction of the appropriate diamine precursors whose synthesis is also reported. sigma receptor affinities ranged from 1.34 nM for 6,7-dichloro-2-[2-(1 pyrrolidinyl)ethyl]tetrahydroisoquinoline (12) to 455 nM for (1R,2R)-trans-N-[2 (3,4-dichlorophenyl)ethyl]-N-methyl-2- (1-pyrrolidinyl)cyclohexylamine [(-)-4]. In this displacement assay, (+)-pentazocine exhibited a Ki of 3.1 nM while DTG and haloperidol showed Ki values of 27.7 and 3.7 nM, respectively. The conformationally free parent compound 1 exhibited a Ki value of 2.1 nM. Comparison of both the sigma receptor affinities and nitrogen atom geometry of the compounds revealed that a gauche relation of the nitrogen atoms of cis-1,2 cyclohexanediamines is not imperative for high affinity as we had previously thought. It is highly likely that nitrogen lone pair orientations and steric factors on the aliphatic portions of these ligands play a major role in the sigma receptor binding of this pharmacophore. PMID- 1447736 TI - Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 2. Synthesis and biological activity of 8-(benzenesulfonamido)-7-(3 pyridinyl)octaonic acid and related compounds. AB - A series of arylsulfonamide alkanoic acids substituted with a 3-pyridinyl group along the aliphatic chain were synthesized and tested in vitro for their ability to antagonize thromboxane A2 (TxA2) receptors and inhibit thromboxane synthase. These compounds were found to potently inhibit the U 46619-induced aggregation of human platelets and to also inhibit TxA2 biosynthesis in a human microsomal platelet preparation. However, some members of the series, notably compound 21, were found to display agonist activity on the rabbit aorta TxA2 receptor. This unwanted agonist activity appeared to be related to the presence of a substituent beta to the arylsulfonamido group. PMID- 1447737 TI - Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 3. Pyridinylalkyl-substituted 8-[(arylsulfonyl)amino]octanoic acids. AB - A series of 8-[(arylsulfonyl)amino]octanoic acids substituted with a pyridinylalkyl group along the chain were synthesized and tested in vitro for their ability to both antagonize the binding of thromboxane A2 to its receptors and to inhibit the thromboxane synthase enzyme. This series of compounds were found to inhibit the U 46619-induced aggregation of human platelets and the U 46619-induced contraction of dog saphenous vein. The compounds also inhibited TxA2 biosynthesis in a human microsomal platelet preparation. The relative position of the pyridinylalkyl and arylsulfonamide groups had significant effects on the thromboxane receptor antagonist (TxRA) activity and thromboxane synthase inhibitor (TxSI) activity. Compounds with the pyridine ring at the 7- or 8 position of the octanoic acid side chain were weakly active as TxSI but behaved as potent TxRA at the platelet receptor for TxA2. However, these compounds were agonists at the vascular receptor. Substitution of the pyridinylalkyl group at the 2- or 3-position resulted in compounds with potent TxSI activity and weak TxRA activity. The activity profile of the compounds with the pyridinylalkyl substitution at the 4-, 5-, or 6-position was very desirable. Compound 22 with a pyridinylpropyl substituent at the 4-position was found to display extremely potent TxRA and TxSI properties. PMID- 1447738 TI - Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 4. 8-[[(4-Chlorophenyl)sulfonyl]amino]-4-(3-(3-pyridinyl) propyl)octanoic acid and analogs. AB - The title compound (10a) and its analogs were synthesized and found to possess two activities, the inhibition of the biosynthesis of thromboxane A2 and antagonism of its receptors. The in vitro and in vivo profile of these compounds as thromboxane receptor antagonists (TxRAs) and thromboxane synthase inhibitors (TxSIs) is described. 10a and its analogs displayed very potent TxRA activity in human washed platelets (IC50 approximately 10(-7)-10(-9) M) and dog saphenous vein (pA2 approximately 9) and also potent TxSI activity (IC50 approximately 10( 9) M). The good bioavailability and the long duration of action of some of these compounds was demonstrated using ex vivo measurement of the TxRA activity upon oral administration to guinea pigs. Compounds 10a, 20, and 33 potently inhibited arachidonic acid induced bronchoconstriction in guinea pigs. PMID- 1447739 TI - Acyl-CoA:cholesterol O-acyl transferase (ACAT) inhibitors. 1. 2-(Alkylthio)-4,5 diphenyl-1H-imidazoles as potent inhibitors of ACAT. AB - A potent, bioavailable ACAT inhibitor may have beneficial effects in the treatment of atherosclerosis by (i) reducing the absorption of dietary cholesterol, (ii) reducing the secretion of very low density lipoproteins into plasma from the liver, and (iii) preventing the transformation of arterial macrophages into foam cells. We have found that a mevalonate derivative 2, which contains a 4,5-diphenyl-1H-imidazol-2-yl moiety, inhibits rat hepatic microsomal ACAT in vitro and produces a significant hypocholesterolemic effect in the cholesterol-fed rat. Structure-activity relationships for analogues of 2 demonstrate that the 4,5-diphenyl-1H-imidazole moiety is a pharmacophore for inhibition of rat microsomal ACAT. PMID- 1447740 TI - Low molecular weight, non-peptide fibrinogen receptor antagonists. AB - The tetrapeptide H-Arg-Gly-Asp-Ser-OH (1) (RGDS), representing a recognition sequence of fibrinogen for its platelet receptor GP IIb-IIIa (integrin alpha IIb beta 3), served as lead compound for the development of highly potent and selective fibrinogen receptor antagonists. Replacement of the N-terminal arginine by p-amidinophenylalanine or the Gly moiety by m-aminobenzoic acid led to compounds which are superior to the lead peptide with regard to activity and selectivity for GP IIb-IIIa vs the closely related vitronectin receptor alpha v beta 3. By random screening [(p-amidinobenzenesulfonamido)ethyl]-p-phenoxyacetic acid derivatives have been identified as fibrinogen receptor antagonists. Further structure-activity relationship studies culminated in the preparation of N-[N-[N (p-amidinobenzoyl)-beta-alanyl]-L-alpha-aspartyl]-3-phenyl-L- alanine (29h, Ro 43 5054) and [[1-[N-(p-amidinobenzoyl)-L-tyrosyl]-4-piperidinyl]oxy]acetic acid (37f, Ro 44-9883), which exhibit very high activity as platelet aggregation inhibitors (IC50s 0.06 and 0.03 microM, respectively, human PRP/ADP) as well as marked selectivity for GP IIb-IIIa vs alpha v beta 3. Since the activity of 37f in dogs declines according to a two-compartment model with an initial phase having a t1/2 of 8 min and a second phase with a t1/2 of 110 min, this compound is a suitable candidate for the development as iv platelet inhibitor. PMID- 1447741 TI - Synthesis and antimuscarinic properties of some N-substituted 5-(aminomethyl)-3,3 diphenyl-2(3H)-furanones. AB - In a study aimed toward developing new, selective antimuscarinic drugs with potential utility in the treatment of urinary incontinence associated with bladder muscle instability, a series of N-substituted 5-(aminomethyl)-3,3 diphenyl-2(3H)-furanones, conformationally-constrained lactone relatives of benactyzine, was prepared. The compounds were examined in several paradigms that measure muscarinic (M1, M2, and M3) receptor antagonist activity. Selected members of the series that displayed potency and/or selectivity in these tests were studied for their effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. These studies revealed that incorporation of the amino functionality into an imidazole or pyrazole ring resulted in some novel, potent, and selective antimuscarinic agents. Appropriate alkyl substitution of position 2 of the imidazole strikingly affected muscarinic, particularly M3, receptor activity and may reflect a complementary site of interaction. Some of the compounds selectively reduced bladder pressure in a cystometrogram (CMG) model without producing concomitant mydriatic and salivary effects. The separate and distinct action of several compounds of this series in these in vivo protocols suggests the possibility of subtypes of muscarinic receptors that may correspond to previously characterized molecular cloned subpopulations. In this article, structure-activity relationships for the series of substituted lactones are discussed. These studies led to the identification of (R)-[(2-isopropyl-1H imidazol-1-yl)methyl]-4,5-dihydro-3,3-diphenyl-2(3H )- furanone (23) as a clinical candidate for treating urinary bladder dysfunction. PMID- 1447742 TI - Thiophene systems. 14. Synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxythieno[3,2-b]pyrans and related compounds as new potassium channel activators. AB - The synthesis and antihypertensive activity of novel 7-(cyclic amido)-6-hydroxy 5,5-dimethylthieno[3,2-b]pyrans and related compounds are described. The compounds were tested for oral antihypertensive activity in spontaneously hypertensive rats (SHR) and selected compounds were evaluated in vitro for increases in 86Rb efflux in rabbit isolated mesenteric arteries. The effects on activity in SHR of lactam ring size, the presence of heteroatoms in the lactam ring, the relative stereochemistry at C-6 and C-7, and the substituents on the thiophene ring are examined. The best racemic compound in this series is 32, trans-5,6-dihydro-6-hydroxy-5,5-dimethyl-2-nitro-7-(2-oxopiperidin -1-yl)-5H- thieno[3,2-b]pyran, which is 10-fold more potent than cromakalim with an ED30 = 0.015 mg/kg in SHR. Compound 32 could be resolved and the antihypertensive activity determined to reside primarily in the (6S,7S)-(-)-enantiomer 41. Surprisingly, the elimination of water to give the enamides 50-52, thiophene isosteres of bimakalim, diminishes activity significantly. PMID- 1447743 TI - Synthesis and biological activity of 4-(diphenylmethyl)-alpha-[(4 quinolinyloxy)methyl]-1-piperazineethanol and related compounds. AB - A series of 4-(diphenylmethyl)-alpha-[(4-quinolinyloxy)methyl]-1-pipe razineethanol and closely related compounds was synthesized and evaluated for cardiac and vascular activity in isolated perfused rat and guinea pig hearts. Compound 1 produced greater inotropic effects in rat hearts than in guinea pig hearts, a phenomenon which was also observed with the prototype agent DPI 201 106. Compound 15 produced an inotropic effect with one-tenth the potency of compound 1. Both compounds 1 and 15 demonstrated direct inotropic and vasodilatory effects when administered iv in anesthetized dogs, although the vasodilatory activity was more pronounced with compound 15 than 1 and DPI compound. Compound 1 lacks the CN moiety which is a key structural requirement in DPI for positive inotropic activity. The synthesis, in vitro, and in vivo evaluations of these agents, and comparative data with DPI-201-106 (compound 17) are reported. PMID- 1447744 TI - A dideazatetrahydrofolate analogue lacking a chiral center at C-6, N-[4-[2-(2 amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L glutamic acid, is an inhibitor of thymidylate synthase. AB - N-[4-[2-(2-Amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl]benzoyl]-L-glutamic acid (15), prepared in five steps from 2-pivaloyl-7 deazaguanine, has been found to be an antitumor agent with its primary site of action at thymidylate synthase rather than purine synthesis. This compound appears to be a promising candidate for clinical evaluation. PMID- 1447745 TI - Cardiotonic agents. Synthesis and cardiovascular properties of novel 2 arylbenzimidazoles and azabenzimidazoles. AB - Novel 2-arylbenzimidazoles and azabenzimidazoles were synthesized, and their inotropic action was evaluated. Changes in left ventricular pressure, dP/dt max, were measured as an index of cardiac contractility. The structural features that impart optimal inotropic activity are presented. The most potent compounds were evaluated orally in conscious dogs with implanted Konigsberg pressure transducers. To investigate the mechanism of action, the most potent compounds were tested for their calcium-sensitizing properties and their potential for the inhibition of phosphodiesterase. Two compounds, 1 and 41, showed interesting in vitro and oral activity without side effects. They have a more potent calcium sensitizing effect than MCI-154 and are under further investigation. PMID- 1447746 TI - 2-(Aminomethyl)chromans that inhibit iron-dependent lipid peroxidation and protect against central nervous system trauma and ischemia. AB - A series of 2-(aminomethyl)chromans was developed as potent inhibitors of iron dependent lipid peroxidation. Compounds within this class are extremely effective at inhibiting lipid peroxidation with IC50's as low as 0.2 microM. Selected members were found to enhance early neurological recovery and survival in a mouse head injury model. In this assay, improvement in the 1-h post-head-injury neurological status (grip test score) by as much as 230% of control was observed. One of the most efficacious compounds (35) was evaluated in two models of cerebral ischemia where significant neuroprotection was observed. These results provide further support for the importance of cerebroprotective antioxidants for the treatment of traumatic and ischemic injury as well as additional evidence for the role of oxygen radicals in postischemic brain damage. PMID- 1447747 TI - Design, synthesis, and biological evaluation of novel 4-substituted 1-methyl 1,2,3,6-tetrahydropyridine analogs of MPTP. AB - The exceptionally good MAO-B substrate properties of several 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) derivatives have prompted studies to evaluate the corresponding properties of tetrahydropyridines bearing heteroatom-linked groups at C-4. The 1-methyl-4-phenoxy-1,2,3,6-tetrahydropyridine analog proved to be an excellent MAO-B substrate. Unlike analogs bearing hydrocarbon substituents at C-4, the resulting dihydropyridinium metabolite did not undergo further oxidation to the pyridinium compound but rather underwent hydrolytic cleavage. This observation has led to studies designed to explore the possibility of developing novel, nontoxic derivatives of MPTP bearing potential pharmacologically active leaving groups at C-4. In this paper we report the results of synthetic and metabolic studies on a series of tetrahydropyridine analogs of MPTP with oxygen, sulfur, and carbamoyloxy derivatives on C-4 which serve as model compounds to evaluate the scope of this prodrug concept. PMID- 1447748 TI - Diamine ligand release from the cisplatin analogue [meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]dichloroplatinum(II) in cell culture medium. AB - The stability of the five-membered chelate ring of the cisplatin analogue [meso 1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]dichloroplatinum(II) was investigated under typical cell culture conditions (IMEM-Richter's medium with 10% fetal calf serum, 37 degrees C). For this purpose, the platinum compound was radiolabeled with tritium in the meta position of the aromatic ring by an acid catalyzed tritium-exchange reaction, and a reversed-phase HPLC assay with radiochemical detection was developed to monitor for the presence of the free diamine ligand in the cell culture medium. A gradual increase in radioactivity attributed to the free diamine was found in medium containing the dichloroplatinum(II) complex (ca. 25% after 24 h), indicating that the diamine ligand was being released from the metal atom. When 1 mM glutathione (GSH) was included in the incubation medium, the amount of free diamine nearly doubled after 24 h, while the amount of radioactivity attributed to serum protein platinum adducts decreased relative to incubations without GSH. On the other hand, the omission of serum from the incubations resulted in a dramatic decrease in the amount of radioactivity eluting under the diamine peak, while the concentrations of the two methionine-Pt adducts, which formed in a 1:1 ratio, rose. Through the use of liquid secondary ion mass spectroscopy, the two methionine-Pt adducts were identified as monomethionine metabolites of the title compound, whereby the two chloride ligands have been replaced by the amino acid. These compounds are probably diastereomers since the sulfur of methionine can coordinate to platinum with equal probability either cis or trans to the R configured benzylamine carbon. On the basis of the chemical shifts of the MeS groups in the 250-MHz 1H NMR, it is concluded that a S,N-five-membered chelate ring is present in these methionine-Pt adducts. PMID- 1447749 TI - Structural features of substituted purine derivatives compatible with depletion of human O6-alkylguanine-DNA alkyltransferase. AB - A series of O6- and S6-substituted purine derivatives were tested for their ability to deplete the human DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) in cell-free extracts from HT29 colon tumor cells and intact HT29 cells. The order of potency was O6-(p-Y-benzyl)-guanine (Y = H, F, Cl, and CH3) > O6-benzyl-2'-deoxyguanosine > O6-(p-Y-benzyl)guanosine (Y = H, Cl, and CH3) > or = a series of 9-substituted O6-benzylguanine derivatives > or = O6 allylguanine > O6-benzylhypoxanthine > O6-methylguanine. A series of 7 substituted O6-benzylguanine derivatives, 2-amino-6-(p-Y-benzylthio)purine (Y = H, CH3), 2-amino-6-[(p-nitrobenzyl)thio]-9-beta-D-ribofuranosylpurine, and 7 benzylguanine were inactive. It is concluded that for efficient AGT depletion, an allyl or benzyl group attached through exocyclic oxygen at position 6 of a 2 aminopurine derivative is required. Activity is preserved with a variety of substituent groups attached to position 9 while substitution at position 7 leads to a complete loss of activity. PMID- 1447750 TI - Iodinated tomoxetine derivatives as selective ligands for serotonin and norepinephrine uptake sites. AB - In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane preparation. Compound 1R,(R)-(-)-N-methyl-3-(4-iodo-2-methylphenoxy)-3 phenylpropanamine , was the most potent and showed high stereoselectivity for 5 HT uptake sites (Ki, R isomer = 0.65 nM, S isomer = 13.9 nM). Changing the position of the methyl group or eliminating the methyl group at the phenoxy ring resulted in a loss of stereoselectivity. Substitution of the methyl group of tomoxetine with iodine gave the R and S isomers of N-methyl-3-(2-iodophenoxy)-3 phenylpropanamine 4R and 4S. These compounds displayed stereoselectivity for the norepinephrine (NE) (Ki values = 0.24 and 9.35 nM for R and S isomers, respectively). The in vitro binding data suggest that 1R and 4R are potential radioiodinated ligands for pharmacological studies of 5-HT and NE uptake sites, respectively. PMID- 1447751 TI - Carbohydrate materials bearing neuraminidase-resistant C-glycosides of sialic acid strongly inhibit the in vitro infectivity of influenza virus. PMID- 1447752 TI - Synthesis and serotonergic pharmacology of the enantiomers of 3-[(N methylpyrrolidin-2-yl)methyl]-5-methoxy-1H-indole: discovery of stereogenic differentiation in the aminoethyl side chain of the neurotransmitter serotonin. PMID- 1447753 TI - Estimation error of Leydig cell numbers in atrophied rat testes due to the assumption of spherical nuclei. AB - In this study, Leydig cell numbers in control and atrophied testes (induced via subcutaneous implants of testosterone plus 17 beta estradiol for 16 weeks; TE implanted) of rats, estimated via the fractionator method (independent of any assumptions) were compared to those estimated via the disector (unbiased, but dependent on shrinkage) and Floderus (assumes spherical particles, dependent on shrinkage) methods. Estimates of Leydig cell numbers in control rats produced by all three stereological methods were similar. In rats with atrophied testes, both the fractionator and the disector methods produced significantly lower (P < 0.01; 47% and 41% with fractionator and disector, respectively) Leydig cell number estimates per testis than in the controls. By contrast, the estimates of Leydig cell number in atrophied testes derived via the Floderus equation were not significantly different from those of controls, but larger than those obtained via the fractionator and the disector methods. These results suggested that the assumptions of the Floderus method were violated in the atrophied rat testes. Why was the Floderus method of estimating Leydig cell number applicable to control rats but not to the TE-implanted rats? In an attempt to answer this question the diameter measurement together with its correction factor used in the Floderus equation (i.e. D+t - 2H) was also derived from the data collected for the disector method. The values for D+t - 2H used in the Floderus method and also calculated via the disector method were found to be identical in controls, but for the TE-implanted rats a 32% lower value was obtained with the Floderus equation when compared to the disector. These findings suggested that this estimation error caused an overestimation of Leydig cell numbers in the TE implanted rat testes. PMID- 1447754 TI - A tilting device for three-dimensional microscopy: application to in situ imaging of interphase cell nuclei. AB - The resolution of an optical microscope is considerably less in the direction of the optical axis (z) than in the focal plane (x-y plane). This is true of conventional as well as confocal microscopes. For quantitative microscopy, for instance studies of the three-dimensional (3-D) organization of chromosomes in human interphase cell nuclei, the 3-D image must be reconstructed by a point spread function or an optical transfer function with careful consideration of the properties of the imaging system. To alleviate the reconstruction problem, a tilting device was developed so that several data sets of the same cell nucleus under different views could be registered. The 3-D information was obtained from a series of optical sections with a Zeiss transmission light microscope Axiomat using a stage with a computer-controlled stepping motor for movement in the z axis. The tilting device on the Axiomat stage could turn a cell nucleus through any desired angle and also provide movement in the x-y direction. The technique was applied to 3-D imaging of human lymphocyte cell nuclei, which were labelled by in situ hybridization with the DNA probe pUC 1.77 (mainly specific for chromosome 1). For each nucleus, 3-D data sets were registered at viewing angles of 0 degrees, 90 degrees and 180 degrees; the volumes and positions of the labelled regions (spots) were calculated. The results also confirm that, in principle, any angle of a 2 pi geometry can be fixed for data acquisition with a high reproducibility. This indicates the feasibility of axiotomographical microscopy of cell nuclei. PMID- 1447755 TI - An appraisal of low-temperature embedding by progressive lowering of temperature into Lowicryl HM20 for immunocytochemical studies. AB - The progressive lowering of temperature (PLT) method of embedding for electron microscope immunolabelling has been examined with the objective of formulating a standardized protocol which can be applied to a wide variety of samples. The methods described cover fixation, processing of samples by the PLT method, embedding in Lowicryl HM20 and subsequent immunolabelling. Each of the steps in the fixation and embedding protocol has been assessed for its potential to retain both morphology and antigenicity. Comparison of samples embedded in Lowicryl K4M and HM20 at -25 degrees C indicate an increased membrane contrast in HM20 sections, and a further improvement in morphology when samples were embedded in HM20 at -50 degrees C rather than at -25 degrees C. The results of applying the methods described are demonstrated in a range of samples of both mammalian and botanical origin, which includes solid tissues, cells in suspension, and cells grown in vitro as a monolayer culture and embedded in situ. Samples processed by this method have been immunolabelled using a wide range of antibodies recognizing nuclear, cytoplasmic, cell membrane and extracellular matrix antigens. PMID- 1447756 TI - Differences in evaluations of communication channels for cancer-related information. AB - This study examined women's evaluations of communication channels which are major carriers of cancer-related information. A sample of women over 40 (n = 395) was asked which channels they had received cancer-related information from within the last year and what their evaluations were of these channels in terms of three dimensions: editorial tone (credibility), communication potential (presentation and style), and utility. Various statistical analyses revealed significant interactions between evaluations and channels and significant main effects for channels and for evaluations. Additional post hoc comparisons suggested that there was a general trend across channel characteristics to rate doctors and organizations more highly than friends/family and the media for providing cancer related information, although the respondents did not perceive information received from doctors and organizations as more understandable or more novel than information obtained from the media. On the whole, friends and family were evaluated least positively. These results are discussed in terms of their relationship to other programmatic research in this area and their pragmatic implications for future cancer control efforts. PMID- 1447757 TI - Antecedents of adherence to medical recommendations: results from the Medical Outcomes Study. AB - A longitudinal study of patients with chronic medical diseases (hypertension, diabetes, heart disease) was conducted to identify antecedents of adherence to medical recommendations. Data are from 1198 patients in three health-care provision systems in Los Angeles, Chicago, and Boston. Nonadherence at the beginning of the study was the strongest predictor of nonadherence 2 years later. Other significant predictors varied by type of adherence outcome. Patients who were younger and who relied upon avoidant coping strategies tended to be less likely to follow their doctor's specific recommendations. Patients who were distressed about their health, used avoidant coping strategies, or who reported worse physical and role functioning were less likely to adhere in general. Patient satisfaction with two features of care (interpersonal quality and financial aspects) was positively related to adherence in some models, but satisfaction with the technical quality of care was negatively associated with adherence to specific recommendations among heart disease patients. Social support contributed to specific adherence among diabetic patients. Implications of the study for medical care providers are discussed. PMID- 1447758 TI - Perceptions of smoking risk as a function of smoking status. AB - Perceptions of the health risks associated with smoking in comparison with not smoking were assessed for the self and the "typical smoker" among four groups of adults: current, former and nonsmokers in the community, and smokers who had joined cessation clinics to help them quit. Comparisons across groups indicated that risk perceptions differed as a function of smoking status. Clinic attendees reported the highest smoking risk and the greatest perceived benefit of not smoking, and community smokers reported the lowest of each. In addition, community smokers were the only group to exhibit an "optimistic bias" (i.e., a perception that they were less vulnerable to health risk than was the typical smoker). Results from this cross-sectional study suggest that the decision to engage in and to stop risky behaviors is related to the perceptions of the health risk associated with those behaviors. PMID- 1447759 TI - Effects of acute exercise on cardiovascular reactivity. AB - Although exercise may modulate cardiovascular reactivity to stress, its acute effects have not been studied extensively. The purpose of this study was to examine over time the acute effects of different durations of aerobic exercise on cardiovascular reactivity to stressors. Twenty-four sedentary men underwent minimal exercise, 1 or 2 hr of stationary cycling at 55% VO2max. Heart rate, blood pressure, and blood catecholamines were measured during cold pressor, Stroop, and public speech tasks 1, 3, and 24 hr after exercise. One or two hours of exercise attenuated blood pressure responses to stress. The attenuation was evident 3 hr following exercise and was most apparent on the cold pressor task. These effects were independent of epinephrine level and stress appraisal. The role of central sympathetic processes in the effects of exercise and methodologic implications are discussed. PMID- 1447760 TI - The effects of female sexual response in coitus on early reproductive processes. AB - Research has shown that infertility and its medical investigation are stressful for couples and have adverse effects on sexual functioning. The purpose of this study was to examine how female sexual functioning could influence aspects of the reproductive process. This question was examined within the context of the postcoital test (PCT) routinely performed during the infertility investigation. The sample consisted of 85 women with a mean age of 30 years (SD = 3.8 years) and a mean infertile period of 2.5 years (SD = 1.1 years). Prior to the physiological examination, women completed a battery of questionnaires about their sexual functioning during the scheduled encounter engaged in for purposes of the PCT and during other nonscheduled encounters. The results indicated that the PCT contributed to deterioration in female sexual functioning, and in turn, a poor sexual response was associated with poorer physiological results. The implications of sexual behavior influencing physiohormonal reproductive factors are discussed. PMID- 1447761 TI - Speech rate, loudness, and cardiovascular reactivity. AB - This paper reports the results of two studies that investigated the relationship between speech rate, loudness, and cardiovascular reactivity (CVR). One study involved the separate manipulation of speech rate and loudness and assessed its effects on CVR during a routine reading task. The second study involved the simultaneous manipulation of both loudness and speech rate and studied its effects on CVR within the context of a personal interview. In both studies, the reduction of speech rate and/or loudness was associated with a significant reduction in CVR. On the other hand, increasing speech rate and/or loudness had no, or only a very minimal, effect on CVR. It is suggested that in the absence of emotional arousal, especially anger-arousal, rapid and loud speech per se is not associated with significant cardiovascular hyperreactivity. On the other hand, our findings suggest that training people to speak slowly and softly may be an effective approach for the control of cardiovascular hyperreactivity. PMID- 1447762 TI - Electromyographic feedback in the treatment of bilateral facial paralysis: a case study. AB - Electromyographic feedback in the treatment of facial paralysis has been shown to be a useful alternative to surgical procedures. In this paper we report on the partial recovery of a 7-year-old patient with congenital bilateral facial paralysis (Moebius syndrome) that had been considered untreatable by medical specialists. Biofeedback of electromyographic activity was provided together with specific instructions, social reinforcement, and exercises that the patient carried out at home. The rehabilitation training lasted 1 year, during which there was a substantial increase in the electromyographic activity of the muscles on both sides of the face. A follow-up after 1 year of discontinuing the treatment showed that the muscle activity had been maintained and that there was a marked improvement in the patient's mood and facial expression. PMID- 1447764 TI - Sovereign immunity (res ipsa loquitur). PMID- 1447763 TI - Why not simple ventricular pacing? The hemodynamics of cardiac pacing for noncardiologists. AB - For many years, cardiac pacing consisted primarily of implanting and following fixed-rate ventricular systems. While this mode of pacing restored a more acceptable rate and in fact reduced mortality, prevented syncope, and brought clinical improvement in patients with acquired complete heart block, that it often failed to restore the degree of wellness provided by the normal electrical conduction sequence became increasingly apparent. This paper contrasts normal cardiac mechanics to those of simple ventricular pacing, making clear why clinical outcome with the latter is often disappointing. An approach to selecting pacing modes for specific abnormalities is outlined. The legitimate role of simple ventricular pacing continues to diminish as physicians turn to more hemodynamically efficient atrial and dual chamber pacing with sensor-mediated rate modulation where appropriate. PMID- 1447765 TI - Media managed politics and medical care. PMID- 1447766 TI - AIDS in children. PMID- 1447767 TI - Grossly positive peritoneal lavage and nontherapeutic laparotomy after abdominal stab wound. AB - Diagnostic peritoneal lavage is often employed in the evaluation of stab wounds of the anterior abdomen and lower chest. This technique is perhaps too sensitive, however, in detecting self-limited solid visceral and abdominal wall injuries. We report five cases of nontherapeutic laparotomies in abdominal stab wound victims who had a grossly positive peritoneal lavage prior to surgery. Previous retrospective data indicate that such "false positive" lavages most commonly result from blood entering the abdominal cavity from the wound, although nonoperative injuries to solid viscera and iatrogenic trauma are sometimes implicated. We review these studies and suggest caution in relying too much on lavage results in determining the need for exploration after abdominal stab wounds. Rather, they must be considered alongside other findings in assessing each individual case. PMID- 1447768 TI - Evaluation of mammographic calcification. AB - Breast calcifications can be classified into ductal, lobular, or miscellaneous types. Analysis is less difficult using this classification. Frequently, the characterization of miscellaneous types is straightforward. The analysis of ductal type and lobular type microcalcifications is more challenging. If they are scattered, the most important determination is whether or not there are casting calcifications present. If so, malignancy cannot be excluded. If clustered, then analysis of their form becomes critical. Teacup or pearl type calcifications are benign. Granular or casting calcifications are malignant. Mammographic calcifications that appear obviously malignant or highly suspicious for malignancy warrant biopsy whether or not a mass is clinically palpable. If calcifications are obviously benign, then routine follow-up at four to six month intervals if there is a high probability that they are benign. Otherwise, they are biopsied at the discretion of the clinician. PMID- 1447769 TI - Mississippi State Board of Medical Licensure annual report July 1, 1990 through June 30, 1991. PMID- 1447770 TI - Behavior modification. PMID- 1447771 TI - "Current opinions" of the Council on Ethical and Judicial Affairs of the American Medical Association. Opinions on practice matters. PMID- 1447772 TI - Vicksburg AIDS clinic could be model for U.S. small towns. PMID- 1447773 TI - The 1992 Walter J. Johnson Prize of $10,000. PMID- 1447774 TI - Mutational analysis of the bacteriophage P1 late promoter sequence Ps. AB - The bacteriophage P1 late promoter sequence Ps controls the expression of the genes in the tail-fibre operon. Transcription from Ps only occurs during the second half of the P1 vegetative growth cycle and is positively regulated by the product of the phage gene 10. In this study degenerate oligonucleotides were used as primers in site-directed mutagenesis reactions in order to construct a large set of point mutations within the late promoter sequence Ps. A total of 35 independent single point mutations was isolated and the mutants were tested for promoter activity. Mutations in the Escherichia coli-like -10 region and in a late operator sequence, containing a symmetric sequence centred around position 22, resulted in significant reductions in promoter strength. Most of these mutations alter base-pairs that are highly conserved among the known late promoter sequences of the P1 family. In addition, insertion mutants that change the spacing between the -10 and the late operator indicate that a special topological arrangement between the two boxes is crucial for late promoter function. These results suggest that the product of gene 10 binds specifically to a late operator in order to activate transcription from P1 late promoter sequences. PMID- 1447775 TI - X-ray structure determination and comparison of two crystal forms of a variant (Asn115Arg) of the alkaline protease from Bacillus alcalophilus refined at 1.85 A resolution. AB - The X-ray structure determination, refinement and comparison of two crystal forms of a variant (Asn115Arg) of the alkaline protease from Bacillus alcalophilus is described. Under identical conditions crystals were obtained in the orthorhombic space group P2(1)2(1)2(1) (form I) and the rhombohedral space group R32 (form II). For both space groups the structures of the protease were solved by molecular replacement and refined at 1.85 A resolution. The final R-factors are 17.9% and 17.1% for form I and form II, respectively. The root-mean-square deviation between the two forms is 0.48 A and 0.86 A for main-chain and side chain atoms, respectively. Due to differences in crystal lattice contacts and packing, the structures of the two crystal forms differ in intermolecular interaction affecting the local conformation of three flexible polypeptide sequences (Ser50-Glu55, Ser99-Gly102, Gly258-Ser259) at the surface of the protein. While the two overall structures are very similar, the differences are significantly larger than the errors inherent in the structure determination. As expected, the differences in the temperature factors in form I and II are correlated with the solvent accessibility of the corresponding amino acid residues. In form II, two symmetry-related substrate binding sites face each other, forming a tight intermolecular interaction. Some residues contributing to this intermolecular interaction are also found to be involved in the formation of the complex between subtilisin Carlsberg and the proteinaceous inhibitor eglin C. This demonstrates that the two symmetry-related molecules interact with each other at the same molecular surface area that is used for binding of substrates and inhibitors. PMID- 1447776 TI - Solution structure of [d(GCGTATACGC)]2. AB - The solution structure of the alternating pyrimidine-purine DNA duplex [d(GCGTATACGC)]2 has been determined using two-dimensional nuclear magnetic resonance techniques and distance geometry methods. Backbone distance constraints derived from experimental nuclear Overhauser enhancement and J-coupling torsion angle constraints were required to adequately define the conformation of the inter-residue backbone linkages and to avoid underwinding of the duplex. The distance geometry structures were further refined by back-calculation of the two dimensional nuclear Overhauser enhancement spectra to correct spin-diffusion distance errors. Fifteen final structures for [d(GCGTATACGC)]2 were generated from the refined experimental distance bounds. These structures all exhibit fully wound B-form geometry with small penalty values (< 1.5 A) against the distance bounds and small pair-wise root-mean-square deviation values (typically 0.6 A to 1.5 A). The final structures exhibit positive base-pair inclination with respect to the helix axis, a marked alternation in rise and twist, and are shorter and wider than classical fiber B-form DNA. The purines were found to adopt a sugar pucker close to the C-2'-endo conformation while pyrimidine sugars exhibited significantly lower pseudorotation phase angles in the C-1'-exo to C-2'-endo range. The minor groove cross-strand steric clashes at pyrimidine-purine steps that would exist in pure B-DNA are attenuated by an increased rise at these steps (and an increased roll angle at TpA steps). Concomitantly the backbone torsion angles of the pyrimidine moieties have larger gamma values, larger epsilon values, and smaller zeta values than the purines. The structures generated by distance geometry methods were also compared with those obtained from restrained molecular dynamics with empirical force-field potentials. The results indicate that the nuclear magnetic resonance/distance geometry approach alone is capable of elucidating most of the salient structural features of double-stranded helical nucleic acids in solution without resorting to empirical energy potentials and without using any structural assumptions from crystallographic data. PMID- 1447777 TI - The interdependence of protein surface topography and bound water molecules revealed by surface accessibility and fractal density measures. AB - To characterize water binding to proteins, which is fundamental to protein folding, stability and activity, the relationships of 10,837 bound water positions to protein surface shape and residue type were analyzed in 56 high resolution crystallographic structures. Fractal atomic density and accessibility algorithms provided an objective characterization of deep grooves in solvent accessible protein surfaces. These deep grooves consistently had approximately the diameter of one water molecule, suggesting that deep grooves are formed by the interactions between protein atoms and bound water molecules. Protein surface topography dominates the chemistry and extent of water binding. Protein surface area within grooves bound three times as many water molecules as non-groove surface; grooves accounted for one-quarter of the total surface area yet bound half the water molecules. Moreover, only within grooves did bound water molecules discriminate between different side-chains. In grooves, main-chain surface was as hydrated as that of the most hydrophilic side-chains, Asp and Glu, whereas outside grooves all main and side-chains bound water to a similar, and much decreased, extent. This identification of the interdependence of protein surface shape and hydration has general implications for modelling and prediction of protein surface shape, recognition, local folding and solvent binding. PMID- 1447778 TI - Solution structure of [d(ATGAGCGAATA)]2. Adjacent G:A mismatches stabilized by cross-strand base-stacking and BII phosphate groups. AB - The solution structure of a rather unusual B-form duplex [d(ATGAGCGAATA)]2 has been determined using two-dimensional nuclear magnetic resonance (2D-NMR) and distance geometry methods. This sequence forms a stable ten base-pair B-form duplex with 3' overhangs and two pairs of adjacent G:A mismatches paired via a sheared hydrogen-bonding scheme. All non-exchangeable protons, including the stereo-specific H-5'S/H-5'R of the 3G and 7G residues, were assigned by 2D-NMR. The phosphorus spectrum was assigned using heteronuclear correlation with H-3' and H-4' reasonances. The complete assignments reveal several unusual nuclear Overhauser enhancements (NOEs) and unusual chemical shifts for the neighboring G:A mismatch pairs and their adjacent nucleotides. Inter-proton distances were derived from time-dependent NOEs and used to generate initial structures, which were further refined by iterative back-calculation of the two-dimensional nuclear Overhauser enhancement spectra; 22 final structures were calculated from the refined distance bounds. All these final structures exhibit fully wound helical structures with small penalty values against the refined distance bounds and small pair-wise root-mean-square deviation values (typically 0.5 A to 0.9 A). The two helical strands exchange base stacking at both of the two G:A mismatch sites, resulting in base stacking down each side rather than down each strand of the twisted duplex. Very large twist angles (77 degrees) were found at the G:A mismatch steps. All the final structures were found to have BII phosphate conformations at the adjacent G:A mismatch sites, consistent with observed downfield 31P chemical shifts and Monte-Carlo conformational search results. Our results support the hypothesis that 31P chemical shifts are related to backbone torsion angles. These BII phosphate conformations in the adjacent G:A mismatch step suggest that hydrogen bonding of the G:A pair G-NH2 to a nearby phosphate oxygen atom is unlikely. The unusual structure of the duplex may be stabilized by strong interstrand base stacking as well as intrastrand stacking, as indicated by excellent base overlap within the mismatch stacks. PMID- 1447779 TI - Homonuclear three-dimensional NOE-NOE nuclear magnetic resonance/spectra for structure determination of proteins in solution. AB - The solution structures of two proteins (CMTI-I, a trypsin inhibitor from Cucurbita maxima, and hisactophilin, an actin binding protein of 118 amino acids) have been determined based on the NOE data derived solely from the homonuclear 3D NOE-NOE magnetic resonance spectroscopy. Two different approaches for extraction of the structural information from the 3D NOE-NOE experiment were tested. One approach was based on the transformation of the 3D intensities into distance constraints. In the second, and more robust approach, the 3D NOE intensities were used directly in structure calculations, without the need to transform them into distance constraints. A new 2D potential function representing the 3D NOE-NOE intensity was developed and used in the simulated annealing protocol. For CMTI-I, a comparison between structures determined with the 3D NOE-NOE method and various 2D NOE approaches was carried out. The 3D data set allowed better definition of the structures than was previously possible with the 2D NOE procedures that used the isolated two-spin approximation to derive distance information. PMID- 1447780 TI - Evaluation of the sequence template method for protein structure prediction. Discrimination of the (beta/alpha)8-barrel fold. AB - A multiple alignment of five (beta/alpha)8-barrel enzymes has been derived from their structure. The eight beta-strands and eight alpha-helices of the (beta/alpha)8-barrel are correctly aligned and the equivalenced residues in these regions fulfil similar structural roles. Each beta-strand has a central core of usually four residues, two residues contribute side-chains to the barrel core and the other two residues are involved in beta-strand/alpha-helix contacts. However, the fold imposes no constraints on the volumes of the residues at either a local or global level: the volume of the beta-barrel core varies between 1088 A3 in glycolate oxidase and 1571 A3 in taka-amylase. Sequence motifs derived from the multiple alignment were scanned against a database of 124 protein sequences, including 17 (beta/alpha)8-barrel enzymes. The results were evaluated in terms of the discrimination of (beta/alpha)8-barrel sequences and the quality of the alignments obtained. One motif was able to identify the top 12% of high scoring sequences as forming (beta/alpha)8-barrels with 50% accuracy and the bottom 50% of sequences as not being (beta/alpha)8-barrel proteins with 100% accuracy. However, in most instances the alignments were poor. The reasons for this are discussed with reference to the (beta/alpha)8-barrel proteins and the sequence motif method in general. PMID- 1447781 TI - Three-dimensional structure of an Fv from a human IgM immunoglobulin. AB - An IgM(kappa) immunoglobulin from a patient (Pot) with Waldenstrom's macroglobulinemia was hydrolyzed with pepsin to release a fragment consisting of the 'variable' (V) domains of the light and heavy chains plus eight residue 'tails' from the 'constant' (C) domains. The crystal structure of this fragment was determined at 2.3 A resolution by molecular replacement and crystallographic refinement methods. When examined separately, the light chain component closely resembles another human kappa chain (Rei) in both the beta-pleated sheet regions and the 'hypervariable' loops. The conserved pleated sheets in the heavy chain are similar to those in the human Kol IgG1 protein, but the third hypervariable loop in particular is different from that in any immunoglobulin structure described to date. As in the Kol protein, this loop blocks the access to any internal active site along the light-heavy chain interface. Unlike the Kol protein, however, the loop does not protrude beyond the boundaries of a conventional antigen combining site. Instead, it forms a very compact structure, which fills almost all residual space between the domains. This is an example of one dominant complementarity-determining region (CDR) essentially negating the diversity possible with five other CDRs in the two chains. Ordered water molecules are associated with light chain constituents along the interface, but not with CDR3 of the heavy chain. In screening exercises the Pot IgM failed to bind a wide variety of peptides. Together, the results suggest that ligand binding can only occur on external surfaces of the protein. These surfaces carry a limited number of side chains usually assigned to CDRs in more typical antibodies. PMID- 1447782 TI - Crystallization, structure determination and least-squares refinement to 1.75 A resolution of the fatty-acid-binding protein isolated from Manduca sexta L. AB - The molecular structure of an insect fatty-acid-binding protein isolated from Manduca sexta L. has been determined and refined to a nominal resolution of 1.75 A. Crystals used in the investigation were grown from 1.6 M-ammonium sulfate solutions buffered at pH 4.5 with 50 mM-sodium succinate, and belonged to space group P2(1) with unit cell dimensions of a = 27.5 A, b = 71.0 A, c = 28.7 A and beta = 90.8 degrees. An electron density map, phased with four heavy-atom derivatives and calculated to 2.5 A resolution, allowed for complete tracing of the 131 amino acid residue polypeptide chain. Subsequent least-squares refinement of the model reduced the R-factor from 46.0% to 17.3% using all measured X-ray data from 30.0 A to 1.75 A. Approximately 92% of the amino acid residues fall into classical secondary structural elements including ten strands of anti parallel beta-pleated sheet, two alpha-helices, one type I turn, three type II turns, four type II' turns and one type III turn. As in other fatty-acid-binding proteins, the overall molecular architecture of the insect molecule consists of ten strands of anti-parallel beta-pleated sheet forming two layers that are nearly orthogonal to one another. A helix-turn-helix motif at the N-terminal portion of the protein flanks one side of the up-and-down beta-barrel. The functional group of the fatty acid is within hydrogen-bonding distance of Gln39, Tyr129, Arg127 and a sulfate molecule, while the aliphatic portion of the ligand is surrounded by hydrophobic amino acid residues lining the beta-barrel. The binding of the carboxylic acid portion of the ligand is very similar to that observed in P2 myelin protein and the murine adipocyte lipid-binding protein, but the positioning of the hydrocarbon tail after approximately C6 is completely different. PMID- 1447783 TI - Anatomy and evolution of proteins displaying the viral capsid jellyroll topology. AB - In this paper the anatomy of 25 structures containing a jellyroll motif, consisting of eight antiparallel beta-strands forming a so-called beta-barrel, was investigated. This involved performing a careful structural alignment based on hydrogen bonds for the equivalent regions of the tertiary folds and a subsequent analysis of conserved amino acids, equivalenced residue-residue contacts, and various parameters describing the size, shape and other geometrical characteristics of these regions. It was found that the jellyroll motif is best viewed as a two-sheet wedge structure rather than a barrel. The more conserved parameters are discussed. A model of evolutionary development for the jellyroll fold in the various protein and viral structures is proposed. PMID- 1447784 TI - Specific interactions between the IclR repressor of the acetate operon of Escherichia coli and its operator. AB - The positions of interference points between the IclR repressor of the acetate operon of Escherichia coli and its specific operator were examined. The number and nature of nucleotides essential to repressor binding were determined by scanning populations of DNA previously methylated at guanine residues by dimethyl sulfate, or depurinated by treatment with formic acid, or depyrimidated by treatment with hydrazine. A total of 46 nucleotides, distributed almost equally between the two strands of the operator region, were found to be functionally important, although to a varying extent. These are clustered in two successive domains which expand from nucleotide -54 to nucleotide -27 and can organize in a palindrome-like structure containing a large proportion of A and T residues. PMID- 1447785 TI - Crystal packing in six crystal forms of pancreatic ribonuclease. AB - We compare the molecular packing of bovine pancreatic ribonuclease A (RNase A) in six crystal forms, two grown with alcohol, three with high salt and one with polyethylene glycol as a precipitant. The six packings differ in the number of molecules in contact and in the extent of the contacts, which bury 1570 A2 to 2790 A2 of the RNase surface. Regions of the protein surface involved in the six packings cover almost the whole RNase molecule. The abundance of polar interactions, about one per 200 A2, is the same in all types of precipitants. All molecule-to-molecule contacts are different in the six crystal forms, except for the one that forms a RNase dimer. The dimer has a large interface covering 1800 A2 and eight to ten polar interactions. Its presence in the three salt-grown crystal forms suggests that it is an intermediate in salt induced crystallization. In contrast, the two alcohol-grown forms contain only small interfaces, implying a different mechanism of nucleation. PMID- 1447786 TI - Thermodynamic stoichiometries of participation of water, cations and anions in specific and non-specific binding of lac repressor to DNA. Possible thermodynamic origins of the "glutamate effect" on protein-DNA interactions. AB - The objective of this study is to quantify the contributions of cations, anions and water to stability and specificity of the interaction of lac repressor (lac R) protein with the strong-binding symmetric lac operator (Osym) DNA site. To this end, binding constants Kobs and their power dependences on univalent salt (MX) concentration (SKobs = d log Kobs/d log[MX]) have been determined for the interactions of lac R with Osym operator and with non-operator DNA using filter binding and DNA cellulose chromatography, respectively. For both specific and non specific binding of lac R, Kobs at fixed salt concentration [KX] increases when chloride (Cl-) is replaced by the physiological anion glutamate (Glu-). At 0.25 M KX, the increase in Kobs for Osym is observed to be approximately 40-fold, whereas for non-operator DNA the increase in Kobs is estimated by extrapolation to be approximately 300-fold. For non-operator DNA, SKobsRD is independent of salt concentration within experimental uncertainty, and is similar in KCl (SKobs,RDKCl = -9.8(+/- 1.0) between 0.13 M and 0.18 M-KCl) and KGlu (SKobs,RDKGlu = -9.3(+/- 0.7) between 0.23 M and 0.36 M-KGlu). For Osym DNA, SKobsRO varies significantly with the nature of the anion, and, at least in KGlu appears to decrease in magnitude with increasing [KGlu]. Average magnitudes of SKobsRO are less than SKobsRD, and, for specific binding decrease in the order [SKobsRO,KCl[>[SKobsRO,KAc[>[SKobsRO,KGlu[ . Neither KobsRO nor SKobsRO is affected by the choice of univalent cation M+ (Na+, K+, NH4+, or mixtures thereof, all as the chloride salt), and SKobsRO is independent of [MCl] in the range examined (0.125 to 0.3 M). This behavior of SKobsRO is consistent with that expected for a binding process with a large contribution from the polyelectrolyte effect. However, the lack of an effect of the nature of the cation on the magnitude of KobsRO at a fixed [MX] is somewhat unexpected, in view of the order of preference of cations for the immediate vicinity of DNA (NH4+ > K+ > Na+) observed by 23Na nuclear magnetic resonance. For both specific and non-specific binding, the large stoichiometry of cation release from the DNA polyelectrolyte is the dominant contribution to SKobs. To interpret these data, we propose that Glu- is an inert anion, whereas Ac- and Cl- compete with DNA phosphate groups in binding to lac repressor. A thermodynamic estimate of the minimum stoichiometry of water release from lac repressor and Osym operator (210(+/- 30) H2O) is determined from analysis of the apparently significant reduction in [SKobsRO,KGlu[ with increasing [KGlu] in the range 0.25 to 0.9 M. According to this analysis, SKobs values of specific and non-specific binding in KGlu differ primarily because of the release of water in specific binding. In KAc and KCl, we deduce that anion competition affects Kobs and SKobs to an extent which differs for different anions and for the different binding modes. PMID- 1447787 TI - Key residues in the allosteric transition of Bacillus stearothermophilus pyruvate kinase identified by site-directed mutagenesis. AB - The structural gene for pyruvate kinase from Bacillus stearothermophilus has been cloned in Escherichia coli and sequenced. The open reading frame from the ATG start codon to the TAG stop codon is 1482 base-pairs and encodes a peptide of relative molecular mass 52,967. In the expression vector pKK223-3, containing the synthetic tac promoter, the gene is overexpressed in E. coli cells to an estimated level of 30% total soluble cell protein. A purification procedure for the overexpressed protein has been established. The construction and characterization of a pair of mutant proteins has given insight into the structural basis of allosteric regulation in the tetrameric enzyme. Substituting tryptophan for tyrosine at position 466 (mutant Trp466-->Tyr) resulted in an activated form of the enzyme, having a reduced K1/2 for the substrate phosphoenolpyruvate. We propose that the characteristics of this mutant might be the result of bulk removal releasing steric inhibition to the formation of an interdomain salt bridge between Asp356 and Arg444. The regulatory behaviour of the double mutant produced by making the additional substitution aspartate for glutamate at position 356 (Trp466-->Tyr/Asp356-->Glu) corroborates this. The position of the salt bridge is such that it might be pivotal to the conformation of a pocket that is proposed to open up when the active R-conformation is adopted. We suggest that the mechanism of activation of B. stearothermophilus pyruvate kinase by ribose-5-phosphate might hinge on an interaction with, or indirectly through, residue Trp466, removing it from the vicinity of the potential salt bridge between Asp356 and Arg444 and thus effecting a closing together of the protein structure concomitant with an opening up of the pocket region. PMID- 1447788 TI - Crystallization and preliminary X-ray investigation of phosphoribosylaminoimidazolesuccinocarboxamide synthase from the yeast Saccharomyces cerevisiae. AB - Crystals of phosphoribosylaminoimidazolesuccinocarboxamide synthase (EC 6.3.2.6) from the yeast Saccharomyces cerevisiae were grown by the vapor diffusion hanging drop technique, using ammonium sulfate as the precipitant. The crystals had dimensions up to 1.2 mm. X-ray diffraction experiments indicated a space group of P2(1)2(1)2(1) and unit cell parameters of a = 62.3 A, b = 63.5 A and c = 80.9 A, with one molecule in the asymmetric unit. Native data have been collected to 2.5 A resolution. PMID- 1447789 TI - Cloning and analysis of the entire Escherichia coli ams gene. ams is identical to hmp1 and encodes a 114 kDa protein that migrates as a 180 kDa protein. AB - We have used an antibody to a previously identified 180 kDa (Hmp1) protein in Escherichia coli to clone the corresponding gene, which encodes a polypeptide of 114 kDa that has a mobility equivalent to 180 kDa in SDS/PAGE. We have demonstrated that the 180 kDa polypeptide is the primary gene product and not due to aggregation with other molecules. Moreover, our data indicate that the highly charged C-terminal region of the protein is responsible for its anomalous behaviour when analysed by SDS/PAGE. The hmp1 gene is in fact identical to ams (abnormal mRNA stability), also designated rne (RnaseE), and reported to have an ORF of 91 kDa. This discrepancy with the data in this paper can be ascribed to the omission of two bases in the previously reported sequence, generating an apparent stop codon. We previously demonstrated that the 180 kDa Hmp1/Ams protein cross reacted with both a polyclonal antibody and a monoclonal antibody raised against a yeast heavy chain myosin. However, we could detect no homology with myosin genes in the ams/hmp1 sequence. From the DNA sequence data, we identified a putative nucleotide binding site and a transmembrane domain in the N-terminal half of the molecule. In the C-terminal half, which appears to constitute a separate domain dominated by proline and charged amino acids, we also identified a region homologous to the highly conserved 70 kDa snRNP protein, involved in RNA splicing in eukaryotes. This feature would be consistent with reports that ams encodes RNaseE, an enzyme required for the processing of several stable RNAs in E. coli. PMID- 1447790 TI - Crystallization and preliminary crystallographic investigation of methanol dehydrogenase from Methylobacterium extorquens AM1. AB - Single crystals of methanol dehydrogenase (MDH) from Methylobacterium extorquens AM1 have been grown by the vapour diffusion method. These crystals diffract to beyond 2 A resolution and are suitable for X-ray crystallography. They belong to the orthorhombic space group P2(1)2(1)2(1) and have the following unit cell parameters: a = 66.79 A, b = 108.9 A, c = 188.9 A. One asymmetric unit contains an alpha 2 beta 2 tetramer of MDH and the location of the non-crystallographic 2 fold symmetry axis of this tetramer is defined by the paired positions of the binding sites of heavy atoms in four MDH-derivatives. PMID- 1447791 TI - The expression, purification and crystallization of the epsilon subunit of the F1 portion of the ATPase of Escherichia coli. AB - The epsilon subunit of the F0F1-ATPase from Escherichia coli has been expressed in E. coli as a fusion protein with glutathione S-transferase from the parasitic helminth Schistosoma japonicum. The epsilon subunit released by thrombin treatment of the purified fusion protein carried two amino acid changes, A1G and M2S, and was obtained in a yield of about five milligrams per litre of cultured cells. The two amino acid changes were shown not to affect function. The protein has been crystallized in a form suitable for X-ray diffraction structure analysis. The crystals are hexagonal, space group P6(1)22 (or P6(5)22), with a = b = 94.9 A, c = 57.1 A and gamma = 120 degrees. The diffraction from small crystals extends to at least 2.9 A resolution. PMID- 1447792 TI - Crystallization of the A-domain of the mannitol transport protein enzyme IImtl. AB - The A-domain of the mannitol transport protein enzyme IImtl from Escherichia coli (relative molecular mass 16,300) was crystallized, both at room temperature and 4 degrees C, from 40% polyethylene glycol 6000 (pH 8.5 to 9.0) using the hanging drop method of vapour diffusion. The crystals have the monoclinic space group P2(1), with unit cell dimensions a = 54.0 A, b = 67.0 A, c = 80.9 A and beta = 100.8 degrees. They diffract to 2.6 A resolution. A self-rotation function and self-Patterson suggest that there are four molecules in the asymmetric unit showing mmm symmetry. PMID- 1447793 TI - Characterization of the nucleic acid-binding activities of the isolated amino terminal head domain of the intermediate filament protein vimentin reveals its close relationship to the DNA-binding regions of some prokaryotic single-stranded DNA-binding proteins. AB - In order to demonstrate that the nucleic acid-binding activities of vimentin are dictated by its Arg-rich N-terminal head domain, this was cut off at position Lys96 with lysine-specific endoproteinase and analysed for its capacity to associate with a variety of synthetic and naturally occurring nucleic acids. The isolated polypeptide (vim NT) showed a preference for single-stranded (ss) polynucleotides, particularly for ssDNAs of high G-content. A comparison of the sequence and predicted secondary structure of vim NT with that of two prokaryotic ssDNA-binding proteins, G5P and G32P of bacteriophages fd and T4, respectively, revealed that the nucleic acid-binding region of all three polypeptides is almost entirely in the beta-conformation and characterized by a very similar distribution of aromatic amino acid residues. A partial sequence of vim NT can be folded into the same beta-loop structure as the DNA-binding wing of G5P of bacteriophage fd and related viruses. As in the case of G5P, nitration of the Tyr residues with tetranitromethane was blocked by single-stranded nucleic acids. This and spectroscopic data indicate intercalation of the Tyr aromatic ring systems between the bases of the nucleic acids and thus the contribution of a stacking component to the binding reaction. The binding was accompanied by significant changes in the ultraviolet absorption spectra of both vim NT and single-stranded nucleic acids. Upon mixing of vim NT with nucleic acids, massive precipitation of the reactants occurred, followed by the quick rearrangement of the aggregates with the formation of specific and soluble association products. Even at very high ionic strengths, at which no electrostatic reaction should be expected, a distinct fraction of vim NT incorporated naturally occurring ssRNAs and ssDNAs into fast sedimenting complexes, suggesting co-operative interaction of the polypeptide with the nucleic acids. In electron microscopy, the complexes obtained from 28 S rRNA appeared as networks of extended nucleic acid strands densely covered with vim NT, in contrast to the compact random coils of uncomplexed RNA. The networks produced from fd DNA were heterogeneous in appearance and their nucleoprotein strands in rare cases were very similar to the rod-like structures of G5P-fd DNA complexes. PMID- 1447794 TI - Genetic analysis of cosB, the binding site for terminase, the DNA packaging enzyme of bacteriophage lambda. AB - cosB, the binding site for terminase, the DNA packaging enzyme of bacteriophage lambda, consists of three binding sites (called R3, R2 and R1) for gpNu1, the small subunit of terminase; and I1, a binding site for integration host factor (IHF), the DNA bending protein of Escherichia coli. cosB is located between cosN, the site where terminase introduces staggered nicks to generate cohesive ends, and the Nu1 gene; the order of sites is: cosN-R3-I1-R2-R1-Nu1. A series of lambda mutants have been constructed that have single base-pair C-to-T transition mutations in R3, R2 and R1. A single base-pair transition mutation within any one of the gpNul binding sites renders lambda dependent upon IHF for plaque formation. lambda phage with mutations in both R2 and R3 are incapable of plaque formation even in the presence of IHF. Phages that carry DNA insertions between R1 and R2, from 7 to 20 base-pairs long, are also IHF-dependent, demonstrating the requirement for a precise spacing of gpNu1 binding sites within cosB. The IHF dependent phenotype of a lambda mutant carrying a deletion of the R1 sequence indicates that IHF obviates the need for terminase binding to the R1 site. In contrast, a lambda mutant deleted for R2 and R1 fails to form plaques on either IHF+ or IHF- cells, indicating terminase binding of R2 is involved in suppression of R mutants by IHF. A fourth R sequence, R4, is situated on the left side of cosN; a phage with a mutant R4 sequence shows a reduced burst size on both an IHF+ and an IHF- host. The inability of the R4- mutant to be suppressed by IHF, plus the fact that R4 does not bind gpNu1, suggests R4 is not part of cosB and may play a role in DNA packaging that is distinct from that of cosB. PMID- 1447795 TI - Protein folding within the cell is influenced by controlled rates of polypeptide elongation. AB - Previous studies have proposed that specific translational pauses have evolved to promote protein folding inside the cell by temporally separating the folding of specific regions of some polypeptide chains during their synthesis. Here we show that this is the case for a bifunctional protein in Saccharomyces cerevisiae. The yeast TRP3 gene contains a translational pause comprising ten contiguous non preferred codons within its second functional domain (indoleglycerol phosphate synthase). Site-directed mutagenesis was used to remove this translational pause by increasing the codon bias of the region without changing the amino acid sequence of the protein (to create the gene TRP3pr: pause replaced). The TRP3pr gene was able to complement a trp3:: URA3 null mutation in yeast. No significant differences in the doubling times of TRP3 or TRP3pr yeast transformants were observed during growth at 25 degrees C, 30 degrees C or 37 degrees C, or in the presence of sublethal concentrations of the analogue, 5-methyltryptophan. However, further analysis of TRP3 and TRP3pr transformants revealed that the removal of the translational pause causes a 1.5-fold decrease in indoleglycerol phosphate synthase activity per TRP3 mRNA. This observation which is statistically significant (P < 0.05) and reproducible, suggests that translational pausing promotes the correct intracellular folding of the TRP3 protein. PMID- 1447796 TI - Genetic analysis of mutations affecting terminase, the bacteriophage lambda DNA packaging enzyme, that suppress mutations in cosB, the terminase binding site. AB - Terminase, the DNA packaging enzyme of phage lambda, binds to lambda DNA at a site called cosB, and introduces staggered nicks at an adjacent site, cosN, to generate the cohesive ends of virion lambda DNA molecules. Terminase also is involved in separation of the cohesive ends and in binding the prohead, the empty protein shell into which lambda DNA is packaged. Terminase is a DNA-dependent ATPase, and both subunits, gpNu1 and gpA, have ATPase activity. cosB contains a series of gpNu1 binding sites, R3, R2 and R1; between R3 and R2 is a binding site, I1, for integration host factor (IHF), the Escherichia coli DNA bending protein. In this work, a series of mutations in Nu1 have been isolated as suppressors of cosB mutations. One of the Nu1 mutations is identical to the previously described Nu1ms1/ohm1 mutation predicted to cause the change L40F in the 181 amino acid-long gpNu1. Three other Nu1 missense mutations, the Nu1ms2 (L40I), ms3 (Q97K) and ms4 (A92G) mutations, have been isolated; the relative strengths of suppression of cosB mutations by the Nu1ms mutations are: ms1 > ms2 > ms3 > ms4. The Nu1 missense mutations all affect amino acid residues that lie outside of the putative helix-turn-helix DNA binding motif of gpNu1. The Nu1ms1 and Nu1ms2 mutations alter an amino acid residue (L40) that lies directly between two segments of gpNu1 proposed to be involved in ATP binding and hydrolysis; thus these mutations are likely to alter the gpNu1 ATP-binding site. The Nu1ms3 and Nu1ms4 mutations both affect amino acid residues in the central region of gpNu1 that is predicted to form a hydrophilic alpha-helix. To explain how the Nu1ms mutations suppress cosB defects, models involving alterations of the DNA binding and/or catalytic properties of terminase are considered. The results also indicate that terminase occupancy of a single gpNu1 binding site (R3) is necessary and sufficient for the efficient initiation of DNA packaging; the Nu1ms1, ms2 and ms3 mutations permit IHF-independent plaque formation by a phage lacking R2 and R1. PMID- 1447797 TI - Role of MotA transcription factor in bacteriophage T4 DNA replication. AB - At least two bacteriophage T4 replication origins, ori(uvsY) and ori(34), contain a T4 middle-mode promoter that is necessary for origin function. We wanted to analyze the requirement of these two replication origins for the MotA protein, which is the phage-encoded activator of middle-mode promoters. To ensure the complete absence of MotA protein, we deleted the motA gene from the T4 genome. Unexpectedly, the deletion mutant was not viable unless the MotA protein was provided from a recombinant plasmid. Therefore, MotA is an essential protein for T4 growth. The motA delta mutation reduced the synthesis of several proteins that are encoded by genes with middle-mode promoters, delayed and reduced the synthesis of late proteins, and substantially reduced phage genomic replication. The motA delta mutation also reduced the replication of an ori(uvsY)-containing plasmid and virtually abolished replication of an ori(34)-containing plasmid. The replication defects of the two origins correlated with transcriptional defects: the motA delta mutation modestly reduced transcription from the plasmid-borne ori(uvsY) promoter and strongly reduced transcription from the ori(34) promoter. These results provide strong evidence that MotA protein is normally involved in origin-dependent replication. However, MotA is not required for origin-directed replication as long as transcription can occur from the origin promoter. PMID- 1447798 TI - [Quantitative cytology--basic researches and clinical applications]. PMID- 1447799 TI - [A historical review of flow cytometers and characteristics of commercial instruments]. AB - Instruments utilized in flow cytometry are called flow cytometers and they can be classified into two kinds, namely, cell analyzers and cell sorters. Important technological developments related to the flow cytometer and various kinds of laboratory instruments are reviewed historically. Commercial cell sorters and cell analyzers produced by several companies are compared and the characteristics of each are listed. PMID- 1447800 TI - [Progress and application of multiple-parameter flow cytometric analysis]. AB - Multiple-parameter flow cytometric analysis for the expression of cell surface markers has been generally used in various clinical and fundamental fields. This was made possible by the development of many monoclonal antibodies and new fluorescence dyes coordinately with the progress in hardwares. Especially, the development of new fluorescence dyes enabled us simultaneously analysis of more than two markers, not only surface markers but also intracellular events, such as Ca2+ concentration and cell cycle. As a result, fine characterization of cells of interest is now possible even with a limited number of cells within a shorter time. The high resolution and sensitivity of current multiple-parameter flow cytometer make possible the isolation of diverse and unique cell populations that can be obtained by no other way. PMID- 1447801 TI - [Applications of flow cytometry to molecular biology and molecular genetics]. AB - Flow cytometry has been utilized in the fields of immunology, hematology, cancer biology and somatic cell genetics. It is also being used for cell cycle and chromosome ploidy analysis. Furthermore, flow cytometry is powerful for karyotype analysis and chromosome sorting. Here, I will review recent advances of flow cytometry in molecular biology and molecular genetics, and discuss some of our recent works. PMID- 1447802 TI - [The theory of flow cytometric analysis of the cell cycle and their applications in biology and oncology]. AB - The clockwise concept of cell cycle kinetics has changed since molecular biology made rapid advances in this area and added somewhat to cell cycle analysis by DNA histogram. During the last decade, it has been made possible to measure many cell cycle-regulating gene products flow cytometrically. Application of bromodeoxyuridine (BrdU) to cell cycle analysis contributes to scientific progression in many fields of biology and oncology. In this article, we attempt to summarize the outline of new concepts regarding the cell cycle by means of flow cytometric techniques and to describe their application in biology and oncology. For this purpose, probes, biological differences amongst the dyes used, DNA analysis using DNA histograms and their limitations are explained. Next, new methods to analyse cell cycle kinetics by means of BrdU, Ki-67 antigen, cyclin, etc. discussed. As far as application of flow cytometric cell cycle analysis are concerned, influences of nutrition, growth factors and hormones, relationships between DNA index or cell cycle and the prognosis of patients with cancer, and the effect of anticancer drugs on the cell cycle are discussed. Finally, we emphasize the importance of multiparameter analysis of cell cycle kinetics using flow cytometry. PMID- 1447803 TI - [Detection of proliferative cells by DNA polymerase a as a proliferation associated marker]. AB - Proliferative cell fractions were measured by flow cytometry in 20 patients with acute leukemia, 4 with chronic myelocytic leukemia in blastic crisis and 7 with malignant lymphoma. The cells were fixed with 2% paraformaldehyde followed by staining with fluorescein isothiocyanate conjugated monoclonal antibody against DNA polymerase a. The DNA polymerase a-positive population was widely distributed in leukemia, from 20.4% to 84.7% in peripheral blood and from 6.5% to 92.5% in the bone marrow. A positive correlation was found between the values in peripheral blood and bone marrow. The values ranged from 66.4% to 88.1% in cells from cases of malignant lymphoma. Cryopreserved cells may be available for measurement of DNA polymerase a because the result obtained in both frozen and fresh cells were essentially the same. PMID- 1447804 TI - [AgNORs (Ag nucleolar organizer regions)]. AB - A quick and quantitative evaluation technique, "AgNORs-FCM", was developed to analyze Nucleolar Organizer Regions (NORs) stained with silver impregnation followed by cytofluorometric analysis. Cell suspension is stained with AgNORs similarly as described elsewhere for tissue sections, but with a modification of using a much lower concentration of silver nitrate. Cytological general rules in AgNORs-FCM are: 1) Specific exaggeration of side scatters (90 LSs) can be detected according to the intensity of AgNORs staining. 2) Significantly brighter 90 LSs were observed when cultured leukemia cell-line was applied to AgNORs-FCM. 3) AgNORs-FCM provides more specifically brighter 90 LS for cells in G2M and S phase, when gated along the P.I.-fluorescence. AgNORs-FCM can be applied to analyze clinico-pathological samples including neoplastic tissues, more quickly and quantitatively, than regular tissue staining with AgNORs. PMID- 1447805 TI - [Flow cytometric analysis, mechanism of action and evaluation of viability by antineoplastic agents]. AB - Since the cell cycle of tumor cells is evaluable with the aid of flow cytometry, the mechanism of action of antineoplastic agents has readily been analyzed based on the changes of the cell cycle by antineoplastic agents. Propidium iodide had been a conventional staining method for such analysis, but after the introduction of DNA/BrdU double staining method using BrdU, it has become much easier. For evaluating antineoplastic agents, simultaneous measurement by FDA of the viability of the tumor cells is important. In vitro studies of the action mechanism and the antineoplastic effects of 5-FU, ACNU, IFN, PG, CDDP, PEP, and HCFU have been reported previously elsewhere. Similar action mechanism has been confirmed in clinical studies, in which optimal agent was selected by the sensitivity test using flow cytometry, and thus selected agent was actually given to tumor patients. In analyzing antineoplastic agents in vitro, concomitant and total evaluation of DNA-histogram and viability by flow cytometry is needed in the future. PMID- 1447806 TI - [Flow cytometric analysis of proliferative characteristics of human leukemic cells in bone marrows in vivo using bromodeoxyuridine (BrdU) and its monoclonal antibody]. AB - We developed a new method for analyzing the proliferative characteristics of human acute leukemic cells in bone marrows in vivo using BrdU and its monoclonal antibody. The thirty minutes after a bolus BrdU infusion, a 1st bone marrow aspiration (BMP) was performed to calculate BrdU-LI. Then, a 150-minute continuous infusion of BrdU was started. After the infusion, a 2nd BMP was done to calculate the increasing rate of the BrdU-LI for 3 hours. Each of the bone marrow cells was analyzed by FCM. A mean value of 10.4% for BrdU-LI in 22 previously untreated patients was obtained. In 3 of the patients, Ts and Tpot ranged from 13.5 to 33.9 hours and 6.8 to 10.7 days respectively. PMID- 1447807 TI - [Chemo-sensitivity test for malignant brain tumors by DNA histogram, in vitro]. AB - Application of flow cytometric DNA analysis was tried to determine the sensitivity of ACNU, one of nitrosourea derivatives which had been used very commonly for malignant brain tumors, to tumor cells. To evaluate the degree of chemo-sensitivity of ACNU, factor B was introduced, indicating the accumulated cells in SG2M phases after ACNU treatment as the percentage of cells that was previously in the SG2M phases and it revealed that ACNU sensitive cell clones gave much larger values of Factor B than ACNU resistant ones at the concentration of 10 micrograms/ml ACNU treatments. Twenty clinical materials obtained by operation were examined by measuring the degree of values of this Factor B, and the findings indicated that this method would be applicable as a clinical test for chemo-sensitivity of malignant brain tumors, after some improvement of the method. PMID- 1447808 TI - [Flow cytometric bromodeoxyuridine (BrdU)/DNA analysis using fresh solid tumors and its clinical significance]. AB - It is very important to determine the biological characteristics of individual cancers, not only in order to evaluate malignant potentials but also to decide on the most effective anticancer therapy. A method which combines BrdU labeling and flow cytometric bromodeoxyuridine (BrdU)/DNA analysis makes it possible to plot the DNA synthetic rate of cells against their DNA content. Hence, this method yields more useful information than the previous method of flow cytometric DNA analysis. When this method is performed correctly, it can be also applied to fresh solid tumors. In this paper, we will describe the results of our preliminary investigation and discuss its clinical significance. PMID- 1447809 TI - [Flow cytometric analysis of the DNA ploidy pattern of primary lung cancer--its prognostic and biological implications]. AB - In order to clarify the significance of the nuclear DNA ploidy pattern in primary lung cancer, recent reports of flow cytometric analysis of nuclear DNA are discussed. It has been reported in many institutes, that nuclear DNA ploidy pattern was a significant and an independent postsurgical prognostic factor in lung cancer, statistically. Diploidy tumors showed a better post-surgical outcome than aneuploid tumors. This fact is more evident in stage I tumor than in advanced cases and was more in squamous cell carcinomas than in adenocarcinomas. Some papers reported that tumors with a high DNA index showed more invasive character than that with a low DNA index with flow cytometric and histopathological examination. As the percentage of aneuploid tumor was much higher in primary lung cancer than in other cancers, more detailed characterization is believed to be needed in aneuploid tumors by means of other oncological analysis, e.g. growth factors or expression of oncogene products. PMID- 1447810 TI - [DNA ploidy pattern as an indicator of degree of malignancy and prognosis in gastric cancer]. AB - We used fresh materials and paraffin blocks of advanced gastric cancer to examine the relationship of DNA ploidy pattern from flow cytometry (FCM) to degree of malignancy and prognosis. No significant relationship was found between the frequency of DNA aneuploid (DA) and the clinicopathological factors (depth of invasion, degree of progression, histological type, lymph node metastasis, ly, v etc.). FCM examination using fresh materials revealed significant difference in prognosis between the non-DA and DA groups for non-curative stage III or IV cases (p < 0.05). On the other hand, in terms of the relationship between DNA ploidy patterns from paraffin blocks and prognosis for curative resection cases of ss gastric cancer, prognosis was significantly better in the non-DA group than in the DA (p < 0.01). These results indicate that the clinicopathological prognostic factors for gastric cancer are connected in a complex way and that DNA ploidy patterns alone are not superior to the prognosis determining factors used in the past. PMID- 1447811 TI - [Study of nuclear DNA content with flow cytometer in pancreatic diseases]. AB - Benign and malignant diseases of the pancreas were compared with nuclear DNA content by flow cytometry, and the relationship between nuclear DNA content and histopathological findings was studied in ductal carcinoma of the pancreas. The nuclear DNA content in the malignant disease was higher than that in the benign disease. No significant correlation between nuclear DNA content and histopathological findings was observed in ductal carcinoma of the pancreas. A tendency for the nuclear DNA content to increase in proportion to the tumor size and the stage was, however, observed. Study of the nuclear DNA content is believed to be an effective adjuvant modality in differential diagnosis between benign and malignant disease of the pancreas. PMID- 1447812 TI - [DNA ploidy pattern of flow cytometry as indicator of degrees of malignancy and prognosis in colorectal cancers]. AB - Cellular DNA content of primary colorectal cancers was measured by flow cytometry and investigated on clinico-pathological features to elucidate the relationship between DNA ploidy patterns and outcomes. IN 144 colorectal carcinomas, DNA diploid carcinomas accounted for 23% and DNA aneuploid carcinomas for 77%. NO significant difference was observed between DNA ploidy pattern and tumor differentiation, lymph node metastasis or lympangial invasion. DNA aneuploid tumor had a tendency to invade vein and to lead to hematogenic metastasis. Patients with DNA aneuploid tumor showed a significantly poor disease-free and overall survival rate. Significantly increased incidence of hematogenic recurrence was demonstrated in the DNA aneuploid cases. These results suggest that the DNA ploidy pattern of colorectal cancers may prove to be of prognostic value. PMID- 1447813 TI - [DNA ploidy pattern of flow cytometry as indicator of malignancy and prognosis in bladder cancer]. AB - Flow cytometry (FCM) of bladder cancer has unique characteristics. First, bladder washing is a suitable material to measure in terms of single cell suspension, while the urine appears inadequate because of the low sensitivity for detecting bladder cancer. Second, the role of FCM depends on the different features of superficial, in situ or invasive bladder cancer. In superficial cancers, FCM can detect the presence of cancer, predict intravesical recurrence and evaluate the response of intravesical instillation therapy. In carcinomas in situ, frequent occurrence of polyclonal aneuploid may indicate the aggressive nature of high grade malignancy. Early removal of bladder may be endorsed unless BCG instillation is effective. For invasive cancers, FCM does not seem to be so useful, but FCM relates well to other prognostic parameters. PMID- 1447814 TI - [Flow cytometric evaluation of DNA ploidy pattern in uterine cancer]. AB - The distribution of DNA ploidy levels and its prognostic significance in cervical cancer (including squamous cell carcinoma and adenocarcinoma) and endometrial cancer is discussed. DNA aneuploidy was observed in most of the cases with either the histological type of cervical cancer and in half of those with endometrial cancer. The DNA ploidy level of the tumor showed a characteristic distribution according to its histological type or grade. Although several investigators have already reported that patients with DNA diploid uterine tumors had a better survival than those with DNA aneuploid uterine tumors, further research is required before a definite conclusion can be attained on the prognostic value of the degree of DNA ploidy measurement in uterine cancer. PMID- 1447815 TI - [Flow cytometric analysis of DNA ploidy pattern in breast cancer: malignant potential and prognostic implication]. AB - Flow cytometric DNA analysis in solid tumors has developed over the past ten years. In human breast cancer, flow cytometric analysis of DNA ploidy pattern recently reported were reviewed. There are conflicting data regarding the value of DNA ploidy pattern obtained by flow cytometric analysis for determining prognosis for breast cancer patients. Some data seem to indicate that S-phase fraction alone or in combination with DNA ploidy pattern may be more important prognostically than DNA ploidy pattern alone, although the results have not been uniform. These suggests that a consensus of determination for DNA ploidy pattern in breast cancer and further investigations on DNA ploidy pattern are required. PMID- 1447816 TI - [Separation and measurement of lymphocyte functional subpopulations by two color FCM method]. AB - With the popularity of flow cytometry (FCM) and the availability of a wide variety of monoclonal antibodies to human blood cells, analysis of cell surface antigens is now conducted at many facilities as part of their routine testing. Analysis of cell surface antigens by FCM has contributed greatly to the diagnosis and the determination of therapeutic effects in many diseases. In the present study, for detection of lymphocyte surface antigens by two color analysis and selection of appropriate antibodies are described. In addition, the significance of two color analysis is explained by citing hematological neoplasms and several other clinical cases. It has been recently reported that the immunological system is involved in many disease processes. In the future, more detailed studies will be conducted to elucidate the immunological mechanisms in these diseases. PMID- 1447817 TI - [Detection of IgG receptor subtype on basophils using two-color FCM]. AB - It was extremely difficult to phenotype basophils because they are most sparse among blood leukocytes. We developed a new method which identified basophils on the basis of negative reactivity with mixed monoclonal antibodies (CD2, CD14, CD16, CD19). Using this method we could detect Fc gamma R II (CDw32) but not Fc gamma R I (CD64) on basophil surface. The method seems useful for the study of clinical allergy and also of the biology of basophil. PMID- 1447818 TI - [Simultaneous analysis of c-myc protein expression and cell cycle with monoclonal antibody and flow cytometry]. AB - C-myc protein plays an important role in the regulation of cell proliferation and differentiation. In this paper, c-myc protein and DNA were doubly stained and analysed simultaneously with flow cytometry (FCM). At first, three fixatives, ethanol, methanol and paraformaldehyde, were examined using HL-60 cells, among which 50% ethanol was found to be optimal for each staining. After fixation, the cells were stained with a monoclonal antibody against c-myc protein, followed by DNA staining with PI. Simultaneous analysis demonstrated that c-myc protein was constantly expressed through the cell cycle and that the protein amount at the G2 + M phases was 1.5 times higher than that at the G1 phase. Further, the differentiation study with TPA and RA revealed that the growth, S phase and also c-myc protein expression were suppressed during the differentiation. PMID- 1447819 TI - [The expression of IL-2 receptor subunits on various leukemic cells]. AB - Interleukin-2 receptors are composed of at least two polypeptide chains of alpha (55KD) and beta (75KD). The IL-2R beta chain is an essential component of the functional receptor for signal transduction of IL-2. We previously reported the distribution of IL-2R subunits among peripheral blood mononuclear cells. We here present some data regarding the expression of IL-2R subunits on various hemopoietic malignant cells. Fresh leukemic cells obtained from adult T cell leukemia patients expressed both alpha and beta chains, and leukemic cells derived from some patients with T cell leukemia, B cell leukemia or myeloid leukemia expressed the alpha and/or beta chain of IL-2R. The IL-2R beta chain on these leukemic cells were demonstrated to be functional for cell growth signaling. IL-2R alpha and beta chains should be tumor markers. PMID- 1447820 TI - [Flow karyotyping and chromosome sorting]. AB - For flow karyotyping and sorting, chromosomes are stained in suspension with appropriate DNA fluorochromes, and passed singly through a beam of laser light. The emitted pulses of fluorescence and scattered light are measured and stored in the form of a histogram displaying the number of pulses versus fluorescence or scattered light intensity. A data processing system was devised to remove signals from cell debris or chromosome fragments. A selective window was set in a dot plot of fluorescence versus scattered light intensities and a program was made to count pulses from the gated area only. As application of chromosome fractionation, flow cytometry has been used for karyotype analysis, gene mapping, and chromosomal DNA library construction. PMID- 1447821 TI - [Flow cytometric analysis of chromosome aberration on tumor cells]. AB - Chromosomal changes plays an important role in malignant transformation. Generally, the process of karyotype instability with grows aneuploidy occurs in tumor. But it is very difficult to obtained Flow karyotype from tumor cells. There are many technical problem in the analysis of chromosomes aberration in tumor cells. Problem is technical procedure of isolation from metaphase chromosomes. It is important to choice of swelling buffer and treatment times. Such technic affect for Flow karyotype pattern. We try to obtained Flow karyotype from chinese hamster cell and V-79 cells and we reported a recent new techniques of cell preparation and chromosomes suspension. PMID- 1447822 TI - [Progress in microscopic image analysis and the trend of image cytometry]. AB - Image cytometry has recently developed prominently based on the digital imaging of cell morphology brought about by great advances in microcomputer hardware and software, electronics etc. This method is characterized by the quantitation of both the amount of intracellular bioactive materials and cell morphology, and is expected to further advance many cell analysis techniques involving automated cytology, chromosome image analysis, automated histopathology, viable cell analysis, 3D image construction, etc. The present use is still minimal, and advances in both hardware and software for cyto-histologic recognition are essentially necessary. Perhaps by the end of this century, more sophisticated and faster machines for automated cyto-histologic analysis will appear, replacing many microscopic techniques of presently subjective observation in the biomedical field. PMID- 1447823 TI - [The advancement of image cytometry in immunohistology]. AB - An image processing system has been developed by the combination of recent electronic and computer technologies. The system may have a potential power for the quantitative analysis on the immunohistology. The image cytometry was applied to quantitative analysis on Ki-67-positive cells in lymphomas of Waldeyer's ring and nasal cavity. High grade lymphomas showed significantly larger number of Ki 67-positive cells than intermediate-grade lymphomas, even analyzed separately by immunophenotypes. A large mean area per Ki-67-positive cell was significantly associated with T-cell phenotype and unfavorable clinical outcome. Thus, Ki-67 immunostaining combined with image cytometry is a novel method for determining a tumor proliferative index which provides useful clinical data of non-Hodgkin's lymphomas. PMID- 1447824 TI - [Quantitative non-radioactive in situ hybridization for measurement of specific mRNA using image analyzer]. AB - To understand cells, information on the state of gene expression in each cell is essential. We determined the copy number of c-myc mRNA in HL60 cell by first carrying out in situ hybridization using thymine-thymine dimerized anti-sense oligonucleotides probes to c-myc mRNA and the hybridized thymine dimers were localized by the immunoperoxidase method. The density of each cell was measured by an image analyzer and converted to the mRNA copy number in each cell, using dot blot hybridization results, as a reference standard. It was found that the numbers of c-myc mRNA copies varied 0-4,000 when expressed at the unit of cell. PMID- 1447825 TI - [The grading of cellular and structural atypia in cancer and related lesions using multivariate analysis]. AB - In morphologically diagnosing cancer, pathologists' attention is focussed on the presence or absence of atypia, i.e., the form of cells and tissues deviated from the norm, and if it is present, on its grade. However, due to retarded development of techniques for the objective evaluation of its grade, separation of cancer from premalignant lesions still meets great ambiguity. Particularly, the boundaries of "dysplasia" with cancer and noncancerous lesions are not defined in clear morphological terms and are susceptible to a strong between observers fluctuation. In this paper we outlined our recent efforts to establish in various organs a statistically most adequate, and therefore reproducible, classification of atypical lesions, resorting to morphometry and multivariate analysis. Two examples were given: atypia of the pancreatic duct epithelia as an object for the study of purely cellular abnormalities, and hepatocellular carcinoma, which required also to quantify the atypia of tissue structures, The classifications thus established proved to be the most adequate, in that, they closely reflected the grade of malignancy in a clinical as well as biological sense, as shown by the clear between-categorier differences in oncogene mutation, DNA ploidy pattern, the patients' prognoses, and so on. PMID- 1447826 TI - [Application of image cytometry to cytological diagnosis of breast tumors]. AB - Computerized morphological analysis of the cell nuclei was performed on 66 cases (2222 nuclei) of aspirated materials from breast tumors: 25 benign cases (302 nuclei), 41 malignant cases (1420 nuclei). Its diagnostic significance and the correlation between nuclear analysis and clinical staging were studied. Nuclear diagram and intranuclear chromatin distribution pattern were evaluated using computer system named 6400. The malignant tumor had larger, more round-shaped nuclei and less uniform chromatin distribution. Under tnm classification, stage IV tumors had larger, more flattened nuclei and more irregular chromatin distribution pattern than the others. Computerized morphological analysis of breast tumors may give a quantitative aspect to classical diagnostic process. Furthermore, this analytical method provides information on clinical stage of breast cancer. PMID- 1447827 TI - [Quantitative DNA image cytometry by color image analyzer]. AB - We developed a new method to analyze DNA quantitatively by a color image analyzer. A microscopic image of the nucleus stained with Feulgen's reaction, is taken by a CCD color camera and inputted in a color image analyzer. DNA quantity can be calculated directly from the RGB components of the color image instead of the monochrome image taken through band-pass filter, which is specific for the absorption of Feulgen's stain. It takes about 10 minutes to measure 500 nuclei by this method and its accuracy is almost the same as flow cytometry (CV = 3%). The nuclear color image can also be analyzed morphometrically. This method can select tumor cells in a usual cytologic specimen and measure their DNA contents. PMID- 1447828 TI - [Confocal laser scanning microscopy for image cytometry]. AB - By using a focused laser beam as the light source of the microscope, to minimized flare, together with a pinhole in front of a photo detector to eliminate out-of focus data, the confocal laser scanning microscope (CLSM) provides a depth discriminated fluorescence image with high spatial resolution. The CLSM, therefore, has been widely used as a tool for accurate morphometric and densitometric analyses. We discussed here the biological applications of CLSM for demonstrating the three-dimensional features of the embryonic heart tube and chromosome and for imaging fast dynamic changes of [Ca2+]i in the living heart muscle cell pairs. PMID- 1447829 TI - [Progress on chromosome image analysis systems]. AB - This is a review of the development of automated systems of chromosome analysis. The history of its development reflects the progress of image analysis systems and that of method of chromosome analysis in man. It can be chronologically summarized as follows. Period I: 1960s-early 1970s when chromosome banding methods were discovered. Period II: early 1970s-early 1980s when the first image analysis system of chromosome was commercialized. Period III: early 1980s present. Research and development of the automated analysis system of radiation induced chromosome aberrations, conducted under the national project of cross over research on underlying technology of nuclear energy, Science and Technology Agency, Japan, is briefly reported. PMID- 1447830 TI - [Advances in molecular parasitology]. AB - Recent studies on molecular biology of parasites revealed novel mechanisms for the control of expression of parasitic genes. In trypanosomatid protozoa, unusual characteristics of gene regulation, including polycistronic transcription, trans RNA splicing and RNA editing have been discovered. This review describes the recent progress of RNA editing in trypanosomes, and trans-splicing in both trypanosomes and nematodes. Studies of the editing of mRNAs in trypanosomatid mitochondria indicate the involvement of small guide RNA molecules, which are encoded in the minicircles and/or maxicircles of kinetoplast DNA. A proposed transesterification model for RNA editing suggests an analogous reaction between RNA editing and RNA splicing. In addition, the development of stable transfection system and success of homologous gene targeting in Trypanosoma and Leishmania are reported. PMID- 1447831 TI - [Effects of smoking and drinking habits and vitamin A intake on serum concentrations of beta-carotene and retinol]. AB - Serum samples from 341 males aged 10 to 59 years were obtained and stored at -40 degrees C until examined for retinol and beta-carotene concentrations by HPLC, and their relationships to smoking habit, alcohol drinking habit and vitamin A intake were studied. In univariate analysis the serum beta-carotene level was significantly lower in the smokers than in the non-smokers (smokers: 4.6 micrograms/dl, non-smokers: 7.1 micrograms/dl, p less than 0.01) and lower in the drinkers than in the non-drinkers (drinkers: 4.6 micrograms/dl, non-drinkers: 7.3 micrograms/dl, p less than 0.01). The serum retinol level was not different by smoking habit but was higher in the drinkers than in the non-drinkers (drinkers: 80.4 micrograms/dl, non-drinkers: 67.0 micrograms/dl, p less than 0.01). Serum beta-carotene was higher in the group with a greater intake of vitamin A of vegetable origin (6.1 micrograms/dl) than in the group with a smaller intake of it (4.7 micrograms/dl) (p less than 0.01), but serum retinol was not different by the amount of vitamin A intake of animal food origin. To estimate the respective effects and interactions of the above factors on serum beta-carotene and retinol levels by adjusting for the confounding effects of age, serum total cholesterol, HDL-cholesterol and triglyceride, analysis of covariance was performed. For serum beta-carotene, smoking habit (p less than 0.01), drinking habit (p less than 0.01) and the amount of vitamin A intake of vegetable food origin (p less than 0.05) had significant main effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447832 TI - [Improved thermogenesis during acute cold exposure in exercise-trained rats]. AB - The present study was carried out to examine the effects of enhanced cold tolerance induced by exercise training on carbohydrate metabolism during cold exposure. Five-week-old male Wistar rats were divided into three groups. The warm acclimated control group (WA) was exposed to the environment at 25 degrees C, and the cold-acclimated group (CA) was acclimated to cold by exposure to 5 degrees C. The exercise-trained group (ET) was controlled to run at the rate of 35 meters per minute for 9 weeks on a small driven treadmill. The degree of carbohydrate metabolism due to cold exposure significantly decreased with the drop in environmental temperature in the WA and CA groups, but did not change in the ET group. When glucose utilization was blocked with 2-deoxyglucose administration, oxygen consumption during cold exposure decreased in the WA and ET groups, but did not decrease in the CA group. The liver glycogen content decreased during cold exposure in the WA and ET groups, but there was no change in the CA group. It appeared that the fall of the plasma glucose level after the infusion of insulin was significantly greater in the ET and CA groups than in the WA group. These results indicate that the improved capacity for cold-induced thermogenesis in the ET group may be caused by enhanced carbohydrate metabolism. PMID- 1447833 TI - [Effects of an essential trace element agent (TE-5) for total parenteral nutrition on the mineral nutrition in rats fed a trace element-deficient diet]. AB - TE-5 is an essential trace element agent containing iron, zinc, copper, manganese and iodine for total parenteral nutrition (TPN). We have already reported that TE 5 improved the reduction of trace element concentrations induced by TPN. However, effects of TE-5 on the changes in biological function relating to trace elements are poorly understood. The present study was designed to clarify the effects of TE-5 on these functions. Rats fed a trace element (iron, zinc, copper, manganese and iodine)-deficient diet for 7 weeks showed reductions in the following parameters: plasma and various tissue concentrations of iron, zinc, copper, manganese and iodine, growth rate, erythrocyte (iron), hemoglobin (iron), hematocrit (iron), mean corpuscular constants (iron), plasma alkaline phosphatase activity (zinc), serum ceruloplasmin concentration (copper), liver pyruvate carboxylase activity (manganese) and serum thyroxine concentration (iodine). On the other hand, when TE-5 (0.008, 0.04 and 0.2ml/kg: x 0.2, x 1 and x 5 the usual clinical dose, respectively) was intravenously administered once a day for 7 weeks under the conditions described above, there was a tendency to prevent the reductions of plasma and various tissue concentrations of iron, zinc and manganese. In addition, TE-5 prevented the reductions of growth rate, iron metabolism functions, plasma alkaline phosphatase activity, serum ceruloplasmin concentration and liver pyruvate carboxylase activity. The present study shows that TE-5 prevents both reductions of trace element contents and trace element related functions, and suggests that TE-5 is useful for treatment of trace element deficiency in TPN. PMID- 1447834 TI - [Effect of cadmium on lipid components: relation of cadmium to thyroid hormone and growth hormone]. AB - To clarify the relationship of cadmium (Cd), thyroid hormone (TH) and growth hormone (GH) to lipid components, 4-week-old SD rats were dosed orally with Cd (CdCl2) at a dose of 2.0 mg/kg body weight five times a week, orally with TH at a dose of 2.5 mg/kg body weight five times a week and subcutaneously with GH (somatotropin) at a dose of 1.0 IU/kg body weight three times a week, all for 4 weeks. As lipid components, the serum concentrations of triglycerides, free fatty acids, lipid peroxides and long-chain fatty acids were determined. We have devised a new method for determining the fatty acid composition in the femur using gas chromatography-mass spectrometry and made a simultaneous analysis of fatty acids, from myristic acid (C14:0) to cholesterol. The results of the present study led to the following conclusions. 1. Cd may inhibit lipogenesis by binding with SH of coenzyme A, thereby reducing the serum levels of free fatty acids and lipid peroxides. 2. When TH and Cd were administered in combination, the addition of Cd produced an inhibitory effect on lipid components, although TH given alone stimulated the lipid metabolism. Therefore, Cd and TH may have an interaction in lipid components. 3. When GH and Cd were administered in combination, Cd modulated the action of GH, which enhanced the effect of somatomedin on the lipid metabolism. The inhibitory effect of Cd on somatomedin activity via Zn was suggested. 4. A sex difference was found in the composition of fatty acids in blood. The males had higher proportions of palmitic acid (C16:0) and linoleic acid (C18:2), while the females had a higher proportion of arachidonic acid (C20:4). There was no sex difference in fatty acid composition in the femur. 5. It was confirmed that TH produced a peroxide of dehydrocholesterol, a precursor of vitamin D3, in the diaphysis of the femur in the increased metabolic state. PMID- 1447835 TI - [The effect of noise on sleep--changes in hypnograms of subjects exposed to repeated truck-passing sound]. AB - The effect of traffic noise on sleep was evaluated in an experimental room using repeated recorded truck-passing sounds. The peak sound level was 55, 60 or 65 dB (A) with frequencies of three times per hour. The background noise of the exposure night was Leq 42 dB (A) and that of the control night was Leq 35 dB (A). The subjects were five students 23 to 24 years old. The sleep stage of each epoch with a 20-second duration was judged visually based on the criteria of Rechtschaffen & Kales and the data of the second night of noise-exposure and the control night were used. The sleep parameters used were total sleep time (TST), each sleep stage, % of sleep stage against TST, sleep efficiencies, sleep latency, REM latency, REM cycle, REM duration, waking from sleep, number of stage shifts, and subjective sleep judged by the OSA sleep inventory. A paired t test was used for the statistical analysis. TST, REM stage in minutes, and % of REM stage against TST of the exposure night were significantly decreased compared with those of the control night. Other objective and subjective parameters showed no changes during noise exposure. Dividing the all-night into halves, the amount and % of each sleep stage were compared between the exposure and control night. There was no change of sleep stage in the former half, but the % and amount of REM sleep in the latter half were significantly decreased as a result of the noise exposure. The decreases of REM sleep and % REM against TST, especially in the latter half of all-night sleep, were caused by the intermittent truck-passing sounds 20 to 30 times per night. PMID- 1447836 TI - [Peripheral airway obstruction and treatment]. AB - The effect of medication on peripheral airway obstruction was examined in cases of bronchial asthma. Subjects were 1) patients with exercise-induced asthma, 2) an animal model of hyperventilation-induced asthma and 3) patients with chronic asthma. Peripheral airway obstruction was induced in 30 of 51 patients with exercise-induced asthma. Induction of peripheral airway obstruction was protected significantly by procaterol. Cromoglycate was effective in 12 of 17 patients but ipratropium was not effective against induction of peripheral airway obstruction. In the animal model, humid air inhalation, procaterol and ipratropium completely prevented hyperventilation-induced bronchoconstriction, but cromoglycate caused only partial prevention. In cases of chronic asthma with peripheral airway obstruction, beclomethasone inhalation reduced the symptom rating rapidly, but no changes were observed in pulmonary function and threshold of airway responsiveness. Cromoglycate was started in patients with chronic asthma who had been treated with beclomethasone. After cromoglycate administration, therapeutic rating decreased, but increased again after 8 weeks of cromoglycate therapy. Peripheral airway obstruction induced by exercise or hyperventilation could be prevented by adequate premedication, but chronic peripheral airway obstruction was difficult to treat. PMID- 1447837 TI - [Circadian rhythm in the treatment of asthma]. AB - The circadian rhythm of respiratory function was examined in normal males and asthmatic subjects. In both groups, maximal flow decreased in the early morning. The major factor contributing to the circadian change in V50 was lung elastic recoil pressure in normal males and upstream resistance in asthmatic subjects. In some asthmatic patients, beclomethasone inhaled in the afternoon and at night was more effective than in the morning in increasing both the circadian maximal and minimal peak expiratory flow rates. This indicates the importance of chronotherapy in asthma. PMID- 1447838 TI - [Features and treatment of immediate and late asthmatic responses]. AB - In atopic asthma, the antigen-induced airway reaction consists of three phases; (1) immediate asthmatic response, LAR, (2) late asthmatic response, LAR, and (3) post-late asthmatic response, pLAR. Election microscopic examination of biopsy specimens of the bronchial mucosa, and examination of desquamated bronchial epithelial cells in sputum after antigen challenge showed that eosinophil infiltration in the bronchial epithelium contributes to airway hyperresponsiveness in asthma. Since LAR and pLAR are considered to be inflammatory responses caused by eosinophil infiltration, suppression of the inflammation by anti-allergic drugs and corticosteroids is effective in the treatment of LAR and pLAR. PAF antagonists and immunosuppressive agents have been investigated for their use in asthma treatment because of their anti-inflammatory effects. In addition to these anti-inflammatory agents, an antagonist of leukotriene C4 and D4 which are potent bronchoconstricting mediators has been shown to suppress both IAR and LAR, suggesting its possible use in asthma treatment. PMID- 1447839 TI - [Clinical study of synchronous multiple primary cancer involving the lung]. AB - Ten cases of synchronous multiple primary cancer involving the lung were experienced in our hospital during the period from January 1962 to May 1987. The incidence rate was 1.3% of all hospitalized cases of primary lung cancer. The counterpart organs were thyroid gland (4 cases), stomach (2 cases), colorectum (2 cases) and lung (2 cases). Three of four thyroid cancer cases were resected at the same time of pulmonary resection, whereas the stomach and colorectal cancer cases underwent two stage operation. Lung perfusion scintigraphy was very useful in determining the operative method for synchronous multiple primary lung cancer. The 5-year survival rate of all cases of synchronous multiple primary cancer involving the lung was 26.3%, with no hospital death. Surgical treatment is recommended for such cases when both cancers are expected to be resected completely. PMID- 1447840 TI - [The effects of oxygen and vasodilators on pulmonary hemodynamics and blood gases in chronic lung disease]. AB - The effects of oxygen inhalation, nitroglycerin (NTG) and prostaglandin E1 (PGE1) on pulmonary hemodynamics and blood gases were studied in 15 patients with chronic lung disease (CLD). Cardiac catheterization was performed with Swan-Ganz catheter, and pulmonary hemodynamics and cardiac output were measured. After baseline hemodynamics and blood gas measurements were made, 15 patients inhaled oxygen for 15 minutes and the same measurements were repeated. Twenty minutes later, oxygen inhalation was stopped. Then the 15 patients were divided into two groups; one group was administered sublingual NTG (7 patients) and the other was administered PGE1 by continuous intravenous infusion (8 patients). Pulmonary hemodynamics and blood gas measurements were then performed. Oxygen inhalation significantly reduced mean pulmonary artery pressure (from 22.2 +/- 8.8 to 20.0 +/- 6.4 mmHg; p < 0.01) and heart rate (from 78.1 +/- 12.0 to 75.5 +/- 12.5 beats/min; p < 0.05). With respect to oxygenation, oxygen inhalation significantly increased PaO2 (from 68.6 +/- 10.7 to 113.4 +/- 31.4 mmHg; p < 0.01), PvO2 (from 35.1 +/- 3.7 to 38.0 +/- 3.3 mmHg; p < 0.01). Therefore, oxygen inhalation was thought to be useful in patients with chronic lung disease with pulmonary hypertension. Sublingual administration of NTG significantly reduced mean pulmonary artery pressure (from 24.1 +/- 0.2 to 17.6 +/- 6.8 mmHg; p < 0.01), C.I. (from 2.9 +/- 0.2 to 2.3 +/- 0.2 ml/min/m; p < 0.01), O2-transport (from 589.1 +/- 168.4 to 457.0 +/- 105.8 ml/min; p < 0.01), and had a tendency to decrease PvO2 (from 34.3 +/- 3.0 to 32.1 +/- 1.8 mmHg; p < 0.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447841 TI - [Six cases of primary pulmonary cryptococcosis]. AB - Six patients with asymptomatic primary pulmonary Cryptococcosis are reported. In all of the patients, the disease was detected by annual chest X-ray during mass screening for lung cancer or during follow-up for pulmonary tuberculosis or gastric cancer. The chest X-ray findings consisted of a solitary pulmonary nodule in 4 patients and multiple pulmonary nodules in 2. Only one patient who could not be histologically diagnosed by bronchofiberscopy underwent surgical resection. However, the other 5 patients were histologically diagnosed by transbronchial biopsy with bronchofiberscopy. They were treated with oral antifungal agents, namely flucytosine (5-FC) and/or fluconazole, with marked improvement of chest X ray findings. These results indicate that transbronchial biopsy with bronchofiberscopy and oral administration of antifungal agents instead of initial surgical resection are useful in the diagnosis and treatment of primary pulmonary cryptococcosis. PMID- 1447842 TI - [Relation of airway obstruction and respiratory muscle weakness to energy metabolism in pulmonary emphysema]. AB - Resting energy expenditure (REE) was assessed and its relationship to nutritional status, pulmonary function and respiratory muscle function was studied in 25 patients with pulmonary emphysema. The mean value of REE was 1413 +/- 251 Cal and the ratio of REE/REEpred was 1.398 +/- 0.23, suggesting the existence of a hypermetabolic state in these patients. REE/REEpred ratio was inversely correlated with plasma amino acid BCAA/AAA ratio and body muscle mass; and PImax. REE was inversely correlated with FEV1.0%. REE in the patient subgroup with severe hyperinflation (%RV > or = 200) was significantly higher than that in the subgroup with moderate hyperinflation. Malnourished patients showed significantly more severe hyperinflation than well-nourished patients. These findings suggest that augmented REE contributes to malnutrition in patients with emphysema, and that the increase in REE was related to the increase in mechanical work load on the basis of airway obstruction, respiratory muscle weakness and hyperinflation. PMID- 1447843 TI - [Characteristics of chronic interstitial pneumonia seen in the lung operated for lung cancer]. AB - A total of 480 lungs operated for lung cancer were reviewed in an attempt to clarify the characteristics of idiopathic chronic interstitial pneumonia (UIP), seen in the cancer bearing lungs. UIP was identified in 30 cases (6.3%). The mean patients age was 68 years, and 26 cases were male. Squamous cell carcinoma was the dominant tumor type (17 cases) and the lower lobe was the dominant location (18 cases). All cancers were situated in the periphery of lungs which had UIP, but not necessarily in the center of the fibrosis. According to extent, UIP is divided into two categories, localized and diffuse types. Twenty-seven cases had localized type UIP. UIP can be divided into another three categories, according to its microscopic findings; Intramural (IM), emphysematous (E), and intraluminal (IL) types. Eight cases had IM-type and 22 cases had E-type UIP. Some IM-type UIP cases showed only increased density of the subpleural space on CT, without visible cysts. E-type UIP cases had no decrease of lung capacity, and showed various sized cysts on CT. Some cases showed postoperative worsening of UIP and acute exacerbation. We feel that the existence of localized UIP (especially emphysematous type) is important in the early detection of cancer, and as a cue for careful post-operative management to prevent serious complications. PMID- 1447844 TI - [Measurement of CA19-9 in bronchial lavage fluid from patients with lung cancer]. AB - Carbohydrate antigen 19-9 (CA19-9) was measured in bronchial lavage fluid in 21 patients with lung cancer and 4 patients with benign lung diseases (2 patients with DPB, 2 patients with BE). Bronchial lavage of the tumor-related bronchus was performed. In normal subjects, levels of CA19-9 in lavage fluid were less than 1000 IU/ml. On the other hand, in 6 patients with lung cancer, levels of CA19-9 were higher than 1000 IU/ml, and in 3 of these cases, CA19-9 levels were higher than 8000 IU/ml. All six three cases were histologically diagnosed as adenocarcinoma. Tumor resected at operation was then stained by antibody recognizing CA19-9. Tumor in cases with high levels of CA19-9 was stained immunohistochemically. These results indicate that measurement of CA19-9 in bronchial lavage fluid of the tumor-related bronchus is a useful auxiliary method in the diagnosis of lung cancer. PMID- 1447845 TI - [The role of bronchial responsiveness to leukotrienes in antigen-induced immediate and late asthmatic response]. AB - In order to clarify the role of leukotriene in the antigen-induced asthmatic response, we carried out mite-antigen, leukotriene D4 (LTD4) and histamine inhalation tests in 21 mite-sensitive atopic asthma patients, and investigated the relationship between the bronchial responsiveness to mite (PD20-Mite) and that to LTD4 and histamine (PD20-LTD4, PD20-Hist). We then compared PD20-LTD4 and PD20-Hist between the groups with and without late asthmatic response (LAR), and investigated the relationship between the peak percentage fall of FEV1.0 in LAR (magnitude of LAR) and PD20-LTD4 and PD20-Hist. There were significant correlations between PD20-LTD4 and PD20-Mite (r = 0.590, p < 0.01), and between PD20-Hist and PD20-Mite (r = 0.669, p < 0.001). The bronchial responsiveness to LTD4 and histamine was significantly higher in the group with LAR. In addition, PD20-LTD4 showed a significant negative correlation with the magnitude of LAR (r = 0.724, p < 0.001). Furthermore we analyzed the relationship between PD20-LTD and the ratio of the magnitude of LAR to that of IAR (immediate asthmatic response), because there was a significant correlation between the magnitude of IAR and that of LAR (r = 0.842, p < 0.001) in 16 asthmatic patients with dual asthmatic response, and found that the correlation coefficient was also very high (r = -0.836, p < 0.001). These results suggest an important role of leukotriene in the antigen-induced asthmatic response. PMID- 1447846 TI - [Sputum leukotrienes in chronic airway diseases and bronchial asthma attacks]. AB - To determine the pathogenetic role of leukotrienes in chronic airway diseases, sputum samples from patients with bronchial asthma (BA), diffuse panbronchiolitis (DPB), sinobronchial syndrome (SBS), and bronchiectasis (BE) were examined for the presence of leukotrienes (LT) C4, D4, E4, B4, all apparently derived from airway inflammatory cells. Sputum samples from 21 patients, including 10 with BA attack (5 atopic type, 5 non-atopic type) and 11 with chronic obstructive airway diseases (3 DPB, 6 SBS, and BE), were studied. Patients expectorated sputum directly into test-tubes containing 80% ethanol. Following ethanol extraction and partial purification by a C18 SEP-PAK column, LTs were further purified by high performance liquid chromatography (HPLC). Fractions from HPLC with elution times corresponding to synthetic LTC4, D4, E4, and B4 were used to quantify LTs by radioimmunoassay. Eosinophils and neutrophils in the sputum (0.5 ml) were counted following Papanicolaou staining. Percentages of eosinophils in sputum were higher in BA, while those of neutrophils were higher in DPB. Sputum levels of LTC4 were 1.2 +/- 1.6 in BA, 0.12 +/- 0.11 in SBS, and 0.42 +/- 0.14 ng/ml in DPB. Those of LTD4 were 0.21 +/- 0.27 in BA, 0.9 +/- 0.13 in DPB, and 0.10 +/- 0.07 in SBS. LTE4 levels were 5.06 +/- 3.83 in DPB and 2.66 +/- 4.32 in BA. Levels of LTB4 were 1.36 +/- 1.19 in DPB, 0.28 +/- 0.27 in BA, 0.12 +/- 0.07 in SBS, and 0.04 +/ 0.04 in BE. In asthmatics, peptide leukotriene content in sputum was higher than that in chronic airway disease patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447847 TI - [Correlation of signal intensity of blood flow in the pulmonary artery on MR images and clinical features of two cases of primary pulmonary hypertension]. AB - ECG-gated spin-echo MR images of the chest were obtained in two patients with primary pulmonary hypertension (PPH). In transverse section at the level of the right main pulmonary artery (rPA), flow signals in the rPA were quantitatively evaluated, and the correlations with MR signal intensity of intravascular flow and data of routine clinical examinations and the severity of clinical manifestations were studied. In one case, the signal intensity of flowing blood markedly increased with exacerbation of hypoxemia and other clinical manifestations. However, in the other case with a stable course, the signal intensity of intravascular flow did not change significantly. Increase of flow signal in the rPA can reflect decrease of flow velocity that may be cause by a state of high pulmonary vascular resistance or low cardiac output. Therefore, it is suggested that MRI is a useful modality to evaluate the severity of disturbance of the pulmonary circulation in PPH. PMID- 1447848 TI - [Two probable cases of adult Williams-Campbell syndrome--advocation of Williams Campbell-type bronchiectasis]. AB - Williams-Campbell syndrome is a unique type of bronchiectasis which shows ballooning during expiration and collapse during inspiration. Its etiology is thought to be a congenital decrease in bronchial cartilage. We experienced two adult cases of Williams-Campbell syndrome. Since the mucociliary transport system was normal in both cases and neither case had chronic sinusitis, these cases differed from sino-bronchial syndrome. Cases of Williams-Campbell syndrome reported in Japan show characteristic bronchography, but a decrease in bronchial cartilage may or may not be present and its congenital nature is very difficult to demonstrate. We therefore advocate referring to such cases of bronchiectasis with these bronchographic characteristics Williams-Campbell-type bronchiectasis, even if a decrease in bronchial cartilage is not observed. PMID- 1447849 TI - [Thrombosis-inducing activity (TIA) in plasma of a patient with lung cancer, which disappeared after radiotherapy]. AB - A 58-year-old man had been suffering from persistent right shoulder pain was admitted following detection of a Pancoast tumor in the right lung. On admission, there was elevation of peripheral platelet count, plasma FDP and fibrinogen levels and thrombosis-inducing activity (TIA) was detected in his plasma. After receiving 30 Gy of Liniack, the mass shadow and the shoulder pain disappeared, which was accompanied by the normalization of laboratory data and the disappearance of TIA from plasma. However, plasma TIA became positive again one month later, in association with reappearance of shoulder pain and elevation of FDP and fibrinogen levels, which were considered due to recurrence of the tumor, 30 Gy of Liniack together with thermotherapy was again given. There was no subsequent recurrence of tumor, nor TIA has been detected for more than 3 years. PMID- 1447850 TI - [Congenital absence of the right main pulmonary artery--a case report]. AB - A 32-year-old man was admitted to hospital for investigation of bloody sputum. Chest roentgenogram showed a decrease in the volume of the right lung, with mediastinal shift to the right. Chest CT examination revealed narrowing of the right main pulmonary artery. Bronchofiberscopic examination was normal. Pulmonary arteriogram demonstrated complete absence of the right pulmonary artery. Cardiac catheterization showed no concomitant cardiac malformation. Therefore, this case was diagnosed as congenital absence of the right main pulmonary artery. PMID- 1447851 TI - [A case of Hodgkin's disease with endotracheal tumor presenting with severe airflow obstruction]. AB - A 22-year-old woman was admitted to our hospital complaining of productive cough and dyspnea even at rest, and marked cervical lymphadenopathy. Marked stridor and orthopnea were observed, and auscultation of the chest revealed widespread expiratory wheeze which was not relieved by bronchodilators administered intravenously. Chest X-ray and CT scan revealed hilar lymphadenopathy and invasive tumor of the mediastinum. Bronchoscopy demonstrated narrowing of the trachea anteriorly and posteriorly and a submucosal nodular tumor protruding from the right anterior wall, causing approximately 90% occlusion of the lumen of the lower third of the trachea, but distal bronchi were intact. Microscopic findings of inguinal lymph node biopsy specimen revealed mixed cellular lymphoma compatible with Hodgkin's disease. Systemic chemotherapy resulted in relief of symptoms, and two months later, the endotracheal tumor had disappeared bronchoscopically, with slight residual stenosis of the trachea. Before treatment, pulmonary function tests indicated markedly impaired forced volume in 1 second in both expiratory and inspiratory cycles, especially in the latter phase. After remission, however, obstructive ventilatory dysfunction was observed. The cause of prolonged air flow obstruction was thought to be marked infiltration and almost total involvement of the tracheal wall by tumor with a nodular appearance of the lumen. Endotracheal tumor in Hodgkin's disease is rare, and there are few reports on pulmonary function associated with intrathoracic involvement of malignant lymphoma. PMID- 1447852 TI - [A case of bucillamine-induced interstitial pneumonia]. AB - Bucillamine [N-(2-mercapto-2-methylpropionyl)-L-cysteine] is an anti-rheumatic drug which was developed in Japan. Interstitial pneumonia induced by bucillamine has been reported in two patients with rheumatoid arthritis. In this report, we describe another patient who developed bucillamine-induced interstitial pneumonia. In August 1990, a 53-year-old man was admitted because of fever, dry cough and dyspnea on exertion (DOE). Five months previously, he had noted polyarthritis, and treatment with bucillamine was started in May 1990. His polyarthritis improved about 2.5 months after starting bucillamine, but he developed fever, dry cough, and DOE in August 1990. Chest X-ray on admission showed diffuse acinar and interstitial shadows predominantly in the bilateral upper lung fields. Pulmonary function tests revealed decreased vital capacity and diffusing capacity. Arterial blood gas (ABG) analysis revealed moderate hypoxemia with PaO2 67 Torr. After stopping bucillamine, the fever, dry cough, and DOE improved gradually, and the abnormal shadows on chest X-ray and ABG analysis showed moderate improvements. Bronchoalveolar lavage studies showed that total cell counts and proportion of lymphocytes were increased, and CD4+/CD8+ ratio of T cell subsets was decreased to 0.56. Transbronchial lung biopsy specimen revealed lymphocytic alveolitis and mild interstitial thickening. Lymphocyte stimulation test to bucillamine was negative, but patch test with bucillamine was positive. From the patient's clinical course, laboratory data, and pathologic findings, we concluded that this is a case of bucillamine-induced interstitial pneumonia. After treatment with corticosteroid, his chest X-ray and pulmonary function test showed marked improvements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447853 TI - [Two cases of idiopathic pulmonary hemosiderosis: analysis of chest CT findings]. AB - Chest CT findings are reported in two cases of idiopathic pulmonary hemosiderosis. In both cases, CT was performed after remission of an acute exacerbation following corticosteroid therapy. Case 1 was a 17-year-old woman with Down's syndrome. Chest radiograph showed diffuse ground-glass like and reticulonodular shadows, which were predominant in the bilateral lower lung fields. Chest CT showed a diffuse increase of lung filed density, especially in the dorsal zone of both lower lobes. Open lung biopsy revealed hemorrhage and numerous hemosiderin-laden macrophages in the alveoli, and in addition, marked fibrous thickening of the alveolar septa. Case 2 was a 7-year-old girl. Chest radiograph showed diffuse micronodular shadows in both lungs. Chest CT showed diffuse poorly-circumscribed micronodular lesions with uniform distribution, and lung field density was normal except for the right upper lobe with patchy infiltrates. Although lung biopsy was not performed, fibrous thickening of the alveolar septa was presumed to be mild even if present, since pulmonary function and blood gas analysis were within normal limits. In these two cases, lung field density of CT seemed to reflect the degree of diffuse fibrous thickening of the alveolar septa, and it is suggested that CT is valuable in the evaluation of fibrous thickening of the alveolar septa secondary to recurrent pulmonary hemorrhages. Comprehensive review of CT findings of idiopathic pulmonary hemosiderosis was also performed. PMID- 1447854 TI - [Sudden death due to bilateral pulmonary thromboembolism in a patient with multiple myeloma: an autopsy case report]. AB - We encountered a patient with multiple myeloma who died suddenly, in whom bilateral pulmonary artery thrombosis was found at autopsy. The patient was a 50 year-old woman who had received chemotherapy for multiple myeloma at a local clinic for 4 years, and was transferred to our hospital because of recurrence of multiple myeloma in August 1990. Despite chemotherapy performed after admission, serum globulin level increased and her low back pain worsened, and she was generally restricted to bed. On October 21, she developed sudden dyspnea, became markedly cyanotic, lost consciousness, and then suffered a cardiopulmonary arrest. Autopsy revealed bilateral pulmonary artery thrombosis as well as thrombosis in the pelvic veins. Hyperviscosity due to multiple myeloma and long term recumbency were the probable causes of pelvic venous thrombosis and subsequent pulmonary artery thrombosis. We report a rare case of bilateral pulmonary artery thrombosis which developed during the course of multiple myeloma and led to sudden death. PMID- 1447855 TI - [A case of superior vena cava syndrome due to extensive venous thrombosis of an idiopathic nature]. AB - A 37-year-old man was admitted with facial edema and right arm swelling. Venography, computed tomography and magnetic resonance imaging showed massive organizing thrombi in the superior vena cava and bilateral internal jugular as well as subclavian veins, and showed no mass lesions occluding the veins in the mediastinum. Angioscopy demonstrated a white thrombus at the entrance of the right subclavian vein. All results of blood coagulation tests were normal. The patient was diagnosed as having superior vena cava syndrome caused by idiopathic venous thrombosis. Anti-coagulant therapy with intravenous tissue plasminogen activator injection and continuous urokinase and heparin infusion into the thrombi through a catheter were not effective in lysing the thrombi. Collateral circulation gradually developed and his symptoms decreased. We decided to follow this patient on warfarin medication because of the difficulty in removing the thrombi surgically. PMID- 1447856 TI - [A case of endoscopic laser polypectomy for endobronchial hamartoma]. AB - A 70-year-old man was admitted to our hospital because of left-sided chest pain and dyspnea. Chest X-ray film showed a tumor in the left main bronchus and left pleural effusion. On bronchoscopy, a tumor which moved with respiration was observed in the left main bronchus. We successfully performed endoscopic laser polypectomy. Pathological examination revealed non-chondromatous hamartoma. PMID- 1447857 TI - [A case of pulmonary alveolar proteinosis and disseminated atypical mycobacteriosis complicating chronic myelogenous leukemia]. AB - A 47-year-old woman with chronic myelogenous leukemia was treated with daily busulfan (total dose approximately 500 mg) from December 1988 to January 1990. The disease thereafter remained stable with no evidence of blastic transformation. In February 1990 she developed productive cough and abnormal acinar lung shadows appeared transiently on her chest X-ray. In October 1990, productive cough and linear and abnormal acinar lung shadows reappeared. Expectorated sputa contained acid-fast bacilli (Gaffky 6, 10). Antituberculous therapy was started, which caused severe liver dysfunction. She was admitted to our hospital for evaluation of abnormal lung shadows. Transbronchial lung biopsy revealed pulmonary alveolar proteinosis with thickening of alveolar septa. The alveolar septal thickening was suspected to be a pathological change following pulmonary alveolar proteinosis. Cultures from sputum, cerebrospinal fluid, and bone marrow aspiration specimens revealed atypical mycobacterium (M. avium complex), and the diagnosis of disseminated atypical mycobacteriosis was established. The pathogenesis of the disseminated atypical mycobacteriosis was considered to be superinfection by mycobacteria. PMID- 1447858 TI - [A case of anomalous course of the pulmonary vein with a tracheobronchus]. AB - A 28-year-old man was admitted to our hospital for further evaluation of a loop like abnormal shadow in the middle lower lung field on chest X-ray film. Pulmonary angiograms demonstrated staining of the abnormal shadow during the venous phase. The abnormal vein descended from the right upper lobe to the middle lobe and then tortuously made a loop upward to drain into the left atrium. A part of the right apical vein was stenosed. The right apical segmental bronchus directly branched from the trachea. These observations indicate that the abnormalities may have originated in the prenatal period. Cases of anomalous course of the pulmonary vein are very rare. PMID- 1447859 TI - Lymehouse blues. PMID- 1447860 TI - Abortion: physician obligations under the new Kansas law. PMID- 1447861 TI - Physician self-referral regulations. PMID- 1447862 TI - Field ecology of Lyme disease in Kansas. PMID- 1447863 TI - Reported cases of Lyme disease in Kansas. PMID- 1447864 TI - The diagnosis and treatment of Lyme disease. AB - Lyme disease has probably been reported for at least 80 years, with the cause unknown until the discovery of the Ixodes ricinus complex tick-borne spirochete B. burgdorferi. The incidence of diagnosed cases appears to be increasing in Kansas and elsewhere. A negative laboratory test does not exclude the possibility of the disease. At present, no accurate laboratory screen for the illness is available. The diagnosis must be considered when acute or chronic clinical manifestations reviewed in this paper appear in patients. Additional clinical criteria and modified CDC guidelines are proposed to help clinicians determine who should be treated. Current treatment recommendations are presented. PMID- 1447865 TI - Syphilis in Ford County, Kansas, 1992. PMID- 1447866 TI - The cost of lowering cholesterol. PMID- 1447867 TI - [Maternity clinics in Finnish maternity care]. PMID- 1447868 TI - [Professional midwifery ethics and comprehensive public health care]. PMID- 1447869 TI - [From village midwife to chairman of the Town Council. Mrs. Margareta Niskanen's 50-year career. Interview by Leena Valvanne]. PMID- 1447870 TI - [The need for professional identity]. PMID- 1447871 TI - [The pedagogic method of family training]. PMID- 1447872 TI - [Experiences of employees about comprehensive public health care in the development of basic health care systems]. PMID- 1447873 TI - [The nonspecific protective reactions and immunological reactivity of the body in peptic ulcer patients]. PMID- 1447874 TI - [Necroses of the lesser curvature of the stomach]. PMID- 1447875 TI - [The basic results of research in surgery in 1986-1990]. PMID- 1447876 TI - [Essays on surgical diagnosis. 1948]. PMID- 1447877 TI - [The treatment of joint cicatricial lesions of the esophagus and stomach]. AB - Treatment of 108 patients with concurrent cicatricial stenosis of the esophagus and stomach is analysed. Various operations were performed on the stomach in 70 patients. The patency of the esophagus was restored by forced bougienage and intubation. The late-term results were studied in 48 patients in follow-up periods of 2-13 years. Forty-two patients feel quite well and are engaged in physical work, they live on a common diet. Six have to chew their food thoroughly. Two patients died in the postoperative period. PMID- 1447878 TI - [Pylorus-preserving gastric resections in gastroduodenal ulcers]. AB - The article analyses the results of pylorus-preserving resections of the stomach in 116 patients among whom 80 had gastric ulcer, 29 ad duodenal ulcer, and 7 had gastroduodenal ulcers. Changes of acidity and motor-evacuation function of the gastric stump were studied according to the method of pylorus-preserving resection. The late-term results of treatment in follow-up periods of 2 to 5 years are shown, they were found to be good in 96.6% of patients treated by operation and poor in 1.7%. It is noted that the function of the gastric stump is better when the vagus innervation of the pylorus is preserved. Mediogastric resection with selective proximal vagotomy in patients suffering from duodenal ulcer with a superacidic stomach led to stable normalization of acid production, which was a reliable measure for the prevention of a recurrent ulcer. PMID- 1447879 TI - [The use of enteral tube feeding in patients with gastric and duodenal peptic ulcer]. AB - The authors used enteral tube feeding with a multicomponent balanced mixture "Ovolakt" in complex treatment of gastric and duodenal ulcer in 69 patients among which 42 had complicated forms (stenosis, penetration, bleeding) and 27 had no complications. In establishing the diagnosis laboratory tests and radiological and endoscopic examination were conducted. The gastric secretory function was studied by intragastric pH-metry and pH-chromoscopy conducted during enteral feeding and in dynamics after it was ended. In most cases of cicatrization of the gastric and duodenal defects, hypo- and hyperchlorhydria respectively, persisted. Among 42 patients with complicated course of peptic disease, 21 were treated by operation and 19 received nonoperative treatment. The postulcer cicatrix formed 2 3 weeks after enteral feeding was ended in 27 cases of uncomplicated peptic ulcer and in 19 patients with complicated ulcers who were given nonoperative treatment. Complications after operative treatment were not encountered. Patients not treated by operation spent 20-30 days in the hospital. PMID- 1447880 TI - [Emergency surgery of the esophagus]. AB - Emergency surgery of the esophagus is undertaken in acute diseases and injuries to the esophagus: among 926 cases of acute pathology of the esophagus 709 were mechanical ruptures of its wall, 380 z (53.6%) of an instrumental character. A rational therapeutic tactics developed at the Institute and basically new methods of treatment allowed the results to be essentially improved and the mortality rate in traumatic purulent mediastinitis to be reduced from 35% to 12%. The total mortality rate in acute surgical pathology in the last 20 years was 9.5%. PMID- 1447881 TI - [The restoration of the natural intestinal passage after Hartmann's operation in a short stump of the rectum]. AB - Analysis showed restorative-reconstructive operations in patients who underwent Hartmann's operation with preservation of a short rectal stump to be technically difficult and injurious interventions. The interventions must be undertaken only after complete removal of the causes of suppuration of the colostomy in a patient whose condition is satisfactory. The degree of the cicatricial process in the pelvis and the method of the colorectal anastomosis formation essentially influence the results of the restorative-reconstructive operations. The best results were produced in retrorectal pull-through of the colon with the formation of colorectal anastomoses after the type of Duhamel's operation. PMID- 1447882 TI - [A comparative evaluation of different methods of forming a colonic anastomosis in repeat surgical interventions]. AB - The results of repeated operations on the large intestine, mainly reconstructive operations, are analysed. Surgical interventions with the performance of a triangular anastomosis, including that by a method modified by the authors, were carried out on 50 patients. The operative results, particularly those in the last group of patients, are very promising. The number of complications, such as suppuration of the postoperative wound and incompetence of the anastomosis sutures, reduced from 28.8% to 10%, which allows the method to be recommended for wide application in the clinic. PMID- 1447883 TI - [The potentials of computed tomography in the treatment of cysts and inflammatory diseases of the internal organs]. AB - Computed tomography (CT) is used more and more often recently in the treatment of some surgical diseases of the internal organs. The subject of discussion in this work are the results of treatment of cysts and pyoinflammatory diseases of the internal organs. The work was conducted on CT IV generation "QUAD 1" of the CMS firm (England). Needles measuring 14-18d in diameter (Charriere scale) were used for aspiration. A total of 23 therapeutic interventions were performed in 19 patients with exudative pleurisy (1 patient), pleuritis (4), pulmonary abscesses (1), abscesses of the liver (1), abscesses of the subhepatic and subdiaphragmatic spaces (2), cysts of the liver (1) and kidneys (1 patient). Among the interventions 21 were aspirations and 2 drainage of the abscess. A mechanical syringe is used lately for more effective evacuation of the contents. The removed contents, ranging in volume from 10.0 to 600.0 ml, was subjected to cytological, biochemical, and bacteriological analysis. A single puncture is sufficient, as a rule, for aspiration of the cyst contents, one-stage aspiration from cysts of both kidneys may be conducted (as was the case in two of our patients). 96% alcohol was used as the sclerosing agent. In cases of small abscesses aspiration may be repeated for removal of the contents, irrigation of the cavity, and administration of antibiotics. In abscesses measuring more than 10 cm drainage is advisable. Control CT examination is conducted once a week. The condition of the cavity is appraised by combining CT with its contrast study. The immediate results were good and satisfactory in 17 (94.7%) patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447884 TI - [Specific immunity in patients with inflammatory diseases of the abdominal cavity]. AB - In most patients with pyoinflammatory diseases of the abdominal cavity caused by Cl. perfringens microbial associations accumulation of agglutinins occurred during the disease. In purulent abdominal processes caused by Cl. perfringens microbial associations a connection exists between the increased antibody level and wound suppuration. The rise of the antibody level was most marked, whatever the character of the bacterial associations, in patients with generalized peritonitis, abdominal abscess, and in young patients (10-40 years of age) and least in those with phlegmonous cholecystitis and in elderly patients (61-70 years of age). Patients with destructive forms of appendicitis and individuals aged 41-60 took an intermediate position according to these values. Antibody production was weaker in patients with 5 species in the microbial association than in monoinfection. A agglutinin titer in the blood of patients beginning with 1:80 and higher should be considered diagnostic. PMID- 1447885 TI - [Combined operations as a method for increasing the capacity of a surgical clinic]. AB - The work shows the economical effect of concurrent surgery on the abdominal organs and organs of the retroperitoneal space undertaken in 404 patients whose ages ranged from 16 to 81. The time taken by the concurrent operations and the duration of treatment at the hospital were studied. In 63.1% of patients the concurrent operations lasted up to 3 hours. The duration of treatment was least in concurrent appendectomy (14.2 +/- 0.5 days) and longest on oncological patients (40.9 +/- 2.2 days). It is noted that the sum terms of treatment reduce, while in separate performance of the operations they are prolonged. The highest economy of finances is noted in urolithiasis, nephroptosis, acute appendicitis, hernias, and cholelithiasis. The national economic effect in the treatment of 404 patients at the clinic came to 60,471 rubles and 18 kopecks. PMID- 1447886 TI - [Means for optimizing the conditions for the timely hospitalization of patients with acute surgical diseases of the abdominal cavity organs]. AB - Complex research made it possible to reveal factors influencing timely hospitalization of patients by studying the causes of timely and late hospitalization, medical erudition of the urban and rural population, as well as the organization of emergency medical service in the prehospital stage. New methodical approaches to health education among the population as well as measures for raising the confidence of the sick in doctors of emergency aid service and surgeons are suggested. From the example of urban health service the authors emphasize the importance of the principle of necessary hospitalization of patients for profound examination in all cases of a doubtful diagnosis of an acute surgical disease. PMID- 1447887 TI - [The mechanisms of the evacuatory function of the gastric stump after a Hofmeister-Finsterer resection]. AB - Attention is drawn to the fact that evacuation from the gastric stump is determined not only by the size of the anastomosis, the manner by which it is formed, whether transversely or longitudinally but also by the functional condition of the gastric stump and the efferent intestinal loop. Motor-evacuation disorders on the part of the stump and efferent intestinal loop precede the development of most postgastric resection syndromes. The authors examined 197 patients who underwent Hofmeister-Finsterer gastrectomy. Five types of evacuation from the gastric stump were distinguished, to which various combinations of motor function of the stump and efferent intestinal loop corresponded. After studying the type of combinations of the motor function of the stomach and efferent intestinal loop, the authors conducted purposeful correction which promoted normalization of the motor function of these organs. For instance, evacuation in portions, which is most efficient in respect of function, was encountered in 42% of patients without correction and in 75.9% of those in whom correction was undertaken. This allowed postoperative functional complications to be reduced from 38% to 12.08% and the adaptation period to be shortened by 2-3 weeks on the average. PMID- 1447888 TI - [Errors, hazards and complications in the treatment of patients with diffuse suppurative peritonitis]. AB - Errors and complications encountered in the treatment of 208 patients with generalized purulent peritonitis are analysed. The importance of preoperative management of patients is shown, when properly conducted it improves the results of treatment. The author discusses tactical and technical errors which are encountered most frequently during the operation and lead to increase of the mortality rate. Rational postoperative management requires particular attention. The immediate results of treatment are improved when errors, hazards, and complications occurring in the treatment of patients with generalized purulent peritonitis are taken into account. PMID- 1447889 TI - [The use of methyldioxyline for the prevention of local complications following hemorrhoidectomy]. AB - The article discusses the results of clinico-laboratory study of the application of methyl dioxyline ointment after hemorrhoidectomy with complete restoration of the anal canal mucosa. It is shown that the ointment is a reliable measure for the prevention of postoperative purulent complications, it improves the reparative processes. Its use in the treatment of wounds developing as the result of excision of hemorrhoids shortens the term of in-patient treatment after the operation and the period of general incapacity. PMID- 1447890 TI - [A method of preparing the large intestine for surgery by using the peroral administration of a polyethylene oxide solution]. AB - A new method for preparing the large intestine for operation is suggested, it is based on oral administration of a solution of polyethylene oxides with chloramphenicol. The preparation possesses a marked hydrophilic activity, which causes inhibition of absorption processes in the lumen of the intestinal tube. This leads to accumulation of the intestinal contents and their quicker passage. Polyethylene oxides also ensure accumulation of antibiotics in the tissues of the intestinal wall. The suggested method was used to prepare the intestine for operation in 93 patients. Comparative evaluation proved its advantages according to the main clinico-laboratory criteria: the method is technically simple, reduces the period of preparation of the intestine, has no negative effect on the homeostasis values, ensures adequate preparation of the large intestine with decrease of the level of its microbial contamination. With the use of the method the number of postoperative purulent complications in interventions on the large intestine reduced. PMID- 1447891 TI - [The modelling of diffuse peritonitis]. AB - Peritonitis is still an urgent problem and its solution is determined to a great measure by purposeful studies in the field of pathogenesis and treatment. The creation of adequate models of peritonitis acquires particular significance. Eighty-four animals (dogs) were used to create the model. It is shown in the work that a standard model of generalized peritonitis can be produced by two injections of a polymicrobial suspension consisting of the most commonly encountered peritoneal microbes E. coli and B. fragilis. The suspension is injected into different levels of the abdominal cavity. With this method of administration of the polymicrobial suspension the model was reproduced in 90% of cases. Thus, the developed model resembles human peritonitis in the clinical picture and the laboratory and morphological values. PMID- 1447892 TI - [Endoscopic interventions in cicatricial strictures of esophageal anastomoses]. AB - Endoscopic balloon hydrodilation was conducted in 39 patients with cicatricial stenoses of esophageal anastomoses, in 12 patients it was combined with electrodissection of the esophageal anastomosis, in 3 with bougienage, and in 10 with temporary endoprosthetics. The anastomosis was dilated adequately (to 2.0 2.5 cm) in 38 patients. In one case endoscopic treatment was ineffective; another surgical intervention was performed. In another case endoprosthetics was complicated by decubitus of the cervical esophagus (favorable outcome). In late term period of 2 months to 4 years restenosis occurred in 6 of 38 patients; the course of dilation was repeated in 4 patients, 2 patients underwent a reconstructive operation. The authors believe that in development of cicatricial stenosis of the esophageal anastomosis modern methods of therapeutic endoscopy should be resorted to in the first place, and only if they prove ineffective should the question of repeated surgical intervention be discussed. Balloon hydrodilation is the principal method of operative endoscopy in cicatricial stenoses of esophageal anastomoses, which in some cases should be combined with other endoscopic interventions (electroincision and temporary endoprosthetics). PMID- 1447893 TI - [An experimental assessment of methods for applying intestinal sutures in intestinal obstruction]. AB - The results of various methods used in applying intestinal sutures in obturation were studied. Three series of experiments were conducted on 30 dogs--resection of the intestine after obstruction with the formation of anastomoses by means of double-row suture (Albert--Shmiden--Lambert) in the first series (10 dogs), by a single-row suture after V. M. Mateshchuk [correction of Mateshuku] in the second series, and bu a single-row stretching suture suggested by the author in the third series. The postoperative complications and the parameters of physical airtightness of the intestinal anastomosis were studied in dynamics in the experimental animals. The results of the study: incompetence of the anastomosis sutures in the first series 6, in the second 4, and in the third series one. Adhesions occurred in all animals of the first and second series and in 2 of the third series. Six dogs of the first series died, 4 of the second, and one of the third. Study of the dynamics of the results showed a direct connection of the complications with the parameters of the physical airtightness of the anastomosis, and the last-named with the method of the intestinal suture. Relatively better results were noted in formation of the anastomosis by means of our suggested stretshing continuous suture passed through the serous, muscular, and submucous coats of the intestine. PMID- 1447894 TI - [The successful treatment of an acute form of Crohn's disease]. PMID- 1447895 TI - [Invagination in an interintestinal anastomosis]. PMID- 1447896 TI - [Eventration of the small intestine through a contra-aperture for drainage of the abdominal cavity]. PMID- 1447897 TI - [Appendicitis in patients with complete situs inversus viscerum]. PMID- 1447898 TI - [The strangulation of a posttraumatic diaphragmatic-pericardial hernia]. PMID- 1447899 TI - [Rupture of an ovarian cyst in a hermaphrodite simulating acute appendicitis]. PMID- 1447900 TI - [The perforation of a gastroduodenal ulcer during the hormonal treatment of viral hepatitis]. PMID- 1447901 TI - [A bladder diverticulum simulating an inguinal hernia]. PMID- 1447902 TI - [Stress disorders of hormonal regulation and metabolism in acute inflammatory diseases of the abdominal cavity complicated by the development of peritonitis]. PMID- 1447903 TI - The use of non-steroidal anti-inflammatory drugs for the relief of pain in laboratory rodents and rabbits. AB - The data concerning the use of non-steroidal anti-inflammatory drugs (NSAIDs) and evidence for their efficacy in laboratory rats and mice are reviewed. This information is then extrapolated to clinical situations and dose rates that take account of ulcerogenic side effects are recommended. NSAIDs have the potential to be a very useful group of analgesics and should always be considered when attempting to provide pain relief in laboratory animals. PMID- 1447904 TI - The scope for improving the design of laboratory animal experiments. AB - The factors which need to be taken into account in designing a 'good' experiment are reviewed. Such an experiment should be unbiased, have high precision, a wide range of applicability, it should be simple, and there should be a means of quantifying uncertainty (Cox 1958). The relative precision due to the use of randomized block designs was found to range from 96% to 543% in 5 experiments involving 30 variables. However, a survey of 78 papers published in two toxicology journals showed that such designs were hardly used. Similarly, designs in which more than one factor was varied simultaneously ('factorial designs') were only used in 9% of studies, though interactions between variables such as dose and strain of animal may be common, so that single factor experiments could be misleading. The consequences of increased within-group variability due to infection and genetic segregation were quantified using data published by Gartner (1990). Both substantially reduced precision, but toxicologists continue to use non-isogenic laboratory animals, leading to experiments with a lower level of precision than is necessary. It is concluded that there is scope for improving the design of animal experiments, which could lead to a reduction in animal use. People using animals should be required to take formal training courses which include sessions on experimental design in order to minimize animal use and to increase experimental efficiency. PMID- 1447905 TI - Subcutaneous administration of HMG-CoA reductase inhibitors in hyperlipidaemic and normal rats. AB - Recent reports demonstrate a hypocholesterolaemic effect of daily subcutaneous injections of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in different rat models of hyperlipidaemia. However, this effect is not seen after oral administration of HMG-CoA reductase inhibitors in rats. We found that oral administration of the HMG-CoA reductase inhibitor Simvastatin also had no effect on plasma cholesterol in severely hyperlipidaemic Nagase analbuminaemic rats (NAR). Simvastatin (an apolar compound dissolved in propylene glycol) was infused continuously for 28 days into the subcutis of control Sprague Dawley rats (SDR) and NAR using an implanted osmotic pump. All doses which were effective in reducing cholesterol in the NAR (reductions up to approximately 60%), reduced apolipoprotein AI but not apolipoprotein B and caused a severe inflammatory reaction in the dermis. Similar toxicity was observed in the SDR. Subcutaneous administration of the vehicle (propylene glycol) did not cause this reaction and did not affect plasma lipids. Administration of Lovastatin in osmotic pumps resulted in a similar inflammatory reaction. Incorporation of Simvastatin into liposomes did not diminish the toxic effect. On the other hand, infusion of Pravastatin (a polar HMG-CoA reductase inhibitor dissolved in isotonic saline) caused no changes in the dermis and had no effect on plasma lipids in NAR or SDR. Liver microsomes prepared from the Pravastatin-treated rats demonstrated a 3- to 4-fold increase in HMG-CoA reductase activity as compared to untreated rats, confirming uptake of the drug. We conclude that continuous subcutaneous administration of the HMG-CoA reductase inhibitors Simvastatin, Lovastatin and Pravastatin for 28 days may not reduce plasma cholesterol in rats by a mechanism which is related to inhibition of HMG-CoA reductase activity in the liver. The decrease of plasma cholesterol effected by subcutaneous infusion of Simvastatin or Lovastatin in NAR coincides with, and may be related to inflammatory changes caused by administering these compounds into the dermis. PMID- 1447906 TI - Struvite urolithiasis in a B6C3F1 mouse. AB - In a 2 year carcinogenicity bioassay using B6C3F1 mice, one male mouse developed clinical signs near termination of the study, comprising skin sores around the prepuce, penile prolapse and urine scalding. The predominant finding at necropsy was a markedly distended urinary bladder filled with numerous crystallized particles. Microscopically, there was subacute cystitis with marked hyperplasia of the transitional epithelium. X-ray diffraction analysis of the crystals showed a diffraction pattern characteristic of struvite (ammonium magnesium phosphate). The implications of the spontaneous occurrence of bladder stones in rodents on long-term toxicology studies are discussed. PMID- 1447907 TI - Spiral bacterium associated with gastric, ileal and caecal mucosa of mice. AB - A spiral shaped bacterium was seen in smears and histological sections (stained by carbolfuchsin) of gastric, ileal and caecal mucosa as well as in stool smears from mice. A significant correlation between the presence of the spiral bacterium and the occurrence of gastritis was observed but the ileal and caecal mucosa seemed unaffected. The bacterium was Gram negative and grew on BHM and Skirrow's medium, under microaerophilic conditions, at 37 degrees C. Its major biochemical characteristics included positive catalase and oxidase reactions and a rapidly positive urease test. There were 2 or 3 spiral turns per cell and a tuft of up to 12 sheathed flagella on each pointed end. Entwined, braided periplasmic fibrils covered the surface of the cell. This spiral bacterium seemed to be part of the normal intestinal flora but was associated with gastritis. PMID- 1447908 TI - Glycosuria and maternal licking in rats. AB - Maternal anogenital licking (MAGL) has been studied to understand the mechanism of maternal behaviour. The present study showed that rats had glycosuria at the concentration of 18-20 mg/dl and glucose was the preference of postpartum rats. MAGL increased on suckling rats separated for 24 h. However, wiping anogenital region attenuated the increase of MAGL. Therefore, glucose preference of postpartum rats may be involved in MAGL. PMID- 1447909 TI - Spinal dysplasia with stump tail and hind limb paralysis in a laboratory bred cat. AB - A case is presented of a specified pathogen free bred cat which was apparently tail-less at birth and at three weeks of age revealed hind limb paralysis. The animal was euthanized at 4 weeks and X-radiography revealed an abnormal spinal curvature, greatly reduced caudal vertebrae and abnormal pelvic development. A small tail was dissected at post-mortem, but other abnormalities were not seen. PMID- 1447910 TI - Can pre-established nephrocalcinosis regress? PMID- 1447911 TI - Fundamental frequency, jitter, and shimmer in preschoolers who stutter. AB - This investigation examined acoustic correlates of phonatory control in the speech of 10 preschool-aged boys who were stutterers (mean age = 45 months) recorded relatively close to the time of stuttering onset and in the speech of 10 boys who were nonstutterers (mean age = 46 months). For each subject, acoustic measurements of fundamental frequency, jitter, and shimmer were extracted from the 100 msec midportion of 30 vowels selected from fluent utterances in spontaneous speech. Significant differences between the two groups for shimmer measures are among the few positive findings in recent publications concerning the fluent speech of children who stutter. PMID- 1447912 TI - The correspondence of vocal tract resonance with volumes obtained from magnetic resonance images. AB - The increasing availability of magnetic resonance imaging (MRI) as a research, and even clinical, tool in speech production makes possible a wide range of quantitative methods in vocal tract measurement. In these initial stages of application, it is essential that the limits of the method be identified. The present investigation was designed to apply the techniques of digital image analysis and volumetric measurement to MRIs obtained for the vocal tract during production of continuant speech sounds, and to apply these measures to a well established and thoroughly tested model of acoustic transmission (Stevens & House, 1955). The results demonstrated that, although there were several sources of relatively large error and measurement bias, the vocal tract volumes obtained from MRIs were significantly predictive of vocal tract resonance frequencies. These results are discussed with respect to limits and potential for future application of MRI to speech production research. PMID- 1447913 TI - Error monitoring in people who stutter: evidence against auditory feedback defect theories. AB - Several theories purport that people who stutter suffer a speech-auditory feedback defect. The disordered feedback creates the illusion that some kind of error has intruded into the speech flow. Stuttering then results from actions aimed to correct the suspected, but nonexistent, error. These auditory feedback defect theories thus predict deviant error detection performance in people who stutter during speech production. To test this prediction, subjects who stuttered and those who did not had to detect self-produced (phonemic) speech errors while speaking with normal auditory feedback and with the auditory feedback masked by white noise. The two groups did not differ significantly in error detection accuracy and speed, nor in false alarm scores. This opposes auditory feedback defect theories and suggests that the self-monitoring processes of people who stutter function normally. In a condition in which errors had to be detected in other-produced speech, i.e., while listening to a tape recording, subjects who stuttered did detect fewer errors. Whether this might signal some general phonological problem is discussed. PMID- 1447914 TI - How can agreement be disagreement? A reply to Christensen. PMID- 1447915 TI - Marching to different drummers: a reply to Smith. PMID- 1447916 TI - Specific-language-impaired children's quick incidental learning of words: the effect of a pause. AB - It was hypothesized that the initial word comprehension of specific-language impaired children would be enhanced by the insertion of a short pause just before a sentence-final novel word. Three groups of children served as subjects: twenty 5-year-old, specific-language-impaired (SLI) children, and two comparison groups of normally developing children, 20 matched for mean length of utterance (MLU) and 32 matched for chronological age (CA). The children were randomly assigned to two conditions for viewing video programs. The programs were animated stories that featured five novel object words and five novel attribute words, presented in a voice-over narration. The experimental version introduced a pause before the targeted words; the control version was identical except for normal prosody instead of a pause. Counter to the predictions, there was no effect for condition. Insertion of a pause did not improve the SLI children's initial comprehension of novel words. There were group main effects, with the CA matches better than either of the other two groups and no differences between the SLI children and the MLU-matched children. PMID- 1447917 TI - The conditions and course of clinically induced phonological change. AB - This two-part study continued the evaluation of minimal pair treatment in phonological change (Gierut, 1989, 1990, 1991a; Gierut & Neumann, 1992). Three linguistic variables relevant to change were experimentally manipulated within an alternating treatments design to determine specifically the interplay of a maximal number of feature distinctions, feature class, and relationship of treated phonemes to a child's grammar in inducing sound change. The conditions of treatment that were shown to facilitate optimal phonological change in previous research were again experimentally replicated. Specifically, minimal pairs comparing two phonemes previously unknown to a child that also differed by maximal and major class features were found to be the preferred context motivating change. Important individual differences emerged and underscored the role of a child's pretreatment grammar in phonological change. These differences contributed to descriptions of possible courses of change followed by children with phonological disorders and bear upon the predictability of change and the effectiveness of treatments that may condition change. PMID- 1447918 TI - Linguistic trade-offs in school-age children with and without language disorders. AB - Factors influencing the occurrence of trade-off effects among linguistic components were examined. Several linguistic measures were used to represent syntactic and phonological production in order to determine whether interrelationship patterns would vary across measures. Linguistic interactions present in imitated speech were compared to those from spontaneous speech. Group effects were explored by comparing data from children with language-learning disabilities, children with reading disabilities, and normally developing children. Results indicated trade-offs between some linguistic measures and positive relationships among others. More trade-offs were present in imitated speech than in spontaneous utterances. In general, interrelationship patterns were similar across groups. Interpretation of these results in reference to current models of sentence production is offered. PMID- 1447919 TI - Grammatical morphology and speech perception in children with specific language impairment. AB - Many English-speaking children with specific language impairment have been found to be especially weak in their use of grammatical morphology. In a separate literature, many children meeting the same subject description have shown significant limitations on tasks involving the perception of rapid acoustic changes. In this study, we attempted to determine whether there were parallels between the grammatical morphological limitations of children with specific language impairment and their performance profiles across several perceptual contrasts. Because most English grammatical morphemes have shorter durations relative to adjacent morphemes in the speech stream, we hypothesized that children with specific language impairment would be especially weak in discriminating speech stimuli whose contrastive portions had shorter durations than the noncontrastive portions. Results from a group of eight children with specific language impairment with documented morphological difficulties confirmed these predictions. Several possible accounts of the observed morphology perception parallels are offered. PMID- 1447920 TI - A study of developmental speech and language disorders in twins. AB - Fifty-seven same-sex twin sets (32 monozygotic and 25 dizygotic) were examined for concordance of speech and language disorders. Results showed monozygotic twins to have higher concordance than dizygotic twins. In addition, monozygotic twins were more similar in the types of disorders they presented than dizygotic twins. Positive family histories for speech, language, and learning disorders were reported in the nuclear families of the twins. PMID- 1447921 TI - Variables influencing perceptions of the communicative competence of an adult augmentative and alternative communication system user. AB - The effects of aided message length, partner reauditorization, and observer background on perceptions of the communicative competence of an adult augmentative and alternative communication (AAC) system user were examined. Two groups of subjects participated: naive adults with minimal exposure to nonspeaking persons, and speech-language pathologists currently working with AAC users. Four scripted videotaped conversational conditions involving an AAC user and a normally speaking partner were employed to manipulate aided message length and partner reauditorization. A balanced incomplete block design was used. Following each viewing, subjects completed a questionnaire designed to assess the communicative competence of the AAC user. Results indicated a significant interaction effect involving subject group and aided message length. The speech language pathologists were affected by aided message length. Furthermore, significant differences between subject groups were found in specific conditions. Future research directions are discussed. PMID- 1447922 TI - Long-term measures of electrode impedance and auditory thresholds for the Ineraid cochlear implant. AB - Measures of electrode impedance and of detection thresholds for electrical stimuli were extracted from the records of patients implanted with the Ineraid cochlear prosthesis. An analysis of impedance measures, obtained at 1, 12, 24, and 36 months after surgery, demonstrated (a) a significant decrease in impedance over the first year for electrodes that carried current and (b) significant increases in impedance at 24 and 36 months for electrodes that did not carry current. An analysis of detection thresholds, obtained at the same times as the impedance measures, demonstrated that averaged thresholds for the current carrying electrodes varied no more than 0.5 dB over the 3-year period. These results support the conclusion that stimulation with the Ineraid device does not produce deleterious changes in the electrodes or in the target neural tissue. PMID- 1447923 TI - Relationships between speech recognition threshold, average hearing level, and speech importance noise detection threshold. AB - The aim of this study was to determine (a) if the speech importance noise detection threshold (SINDT) could be used as an accurate estimator of speech recognition threshold (SRT), and (b) whether the SINDT correlates well with various measures of the pure-tone threshold average (PTA). Pure-tone threshold, SRT, and SINDT tests were administered to 94 adults with various degrees of hearing loss. The results demonstrated that SRT can be accurately predicted from SINDT and that these two are highly correlated (r = 0.97). Since a SINDT measurement takes less time than SRT determination, the SINDT test may be recommended as an alternative for SRT in some applications. PMID- 1447924 TI - The role of localization in visual reinforcement audiometry. AB - The response task employed in visual reinforcement audiometry (VRA) has been characterized both as a localization response and, alternatively, as a pure operant conditioning behavior independent of localization. This study examined the role of localization in VRA conditioning and threshold procedures by varying the localization information provided to normal infants. Results indicate (a) that the VRA response is not contingent on localization but (b) that performance may be significantly influenced by localization. The findings suggest that any variable that alters proper localization cues, including equipment arrangement or impaired auditory function, may degrade response performance. PMID- 1447925 TI - Distortion-product emissions and auditory sensitivity in human ears with normal hearing and cochlear hearing loss. AB - Distortion product emissions (DPEs) at 2f1-f2 frequencies were measured in 53 human ears; 21 of them exhibited cochlear hearing loss. DPEs were obtained as a function of stimulus level (DPE growth curves) at seven frequency regions between 707 Hz and 5656 Hz. Several distinctly different shapes or patterns of DPE growth curves were observed. These included single-segment monotonic growth curves with and without saturation at moderate and high stimulus levels, diphasic growth curves with nulls at moderate stimulus levels, and non-monotonic growth curves with negative slopes at high stimulus levels. Low-level, irregularly shaped segments were more frequent in normal-hearing ears, suggestive of normal low level active nonlinearities from the outer-hair-cell subsystem. High-level, steeply sloped segments were frequent in hearing-impaired ears, suggestive of residual nonlinearities from a cochlear partition without functional outer hair cells. The stimulus level at which the DPE could just be distinguished from the noise floor, the DPE detection threshold, demonstrated moderate positive correlations (r's from 0.50 to 0.81) with auditory thresholds when all ears, both normal and impaired, were considered together. Those correlations were not strong enough to quantitatively predict auditory thresholds with any great accuracy. However, DPE thresholds were able to predict abnormal auditory sensitivity with some precision. DPE thresholds correctly predicted abnormal auditory sensitivity 79% of the time in the present study, and up to 96% of the time in previous studies. These results suggest that DPE thresholds may prove useful for hearing screening in cases where cooperation from the subject is limited or where corroboration of cochlear hearing loss is required. Different patterns of DPE growth curves suggest underlying micro-mechanical differences between ears, but the differential diagnostic value of those patterns remains to be determined. PMID- 1447926 TI - Speechreading enhancement by voice fundamental frequency: the effects of Fo contour distortions. AB - Recognition of words in sentences of known topic was measured in normally hearing adults via speechreading alone and speechreading supplemented with auditory presentation of signals intended to convey variations of voice fundamental frequency (Fo) over time. Three signals were used: (a) the low-pass filtered output of an electroglottograph (unprocessed Fo), (b) a constant amplitude sine wave whose instantaneous frequency was intended to equal that of Fo (processed Fo), and (c) the same sine wave restricted to a small number of discrete frequency steps (quantized Fo). As the number of steps in the quantized Fo contours increased from 1 to 12, the speechreading enhancement effect increased. The quantized Fo contour with 12 steps was as effective as the processed Fo contour (without quantization), but this processed contour was significantly less effective than the unprocessed electroglottograph signal. The results show that the auditory Fo speechreading enhancement effect is sensitive to the errors introduced by the Fo extraction and regeneration process used in this study. It is also sensitive to the quantization of Fo contours into less than 12 steps. Whether more than 12 steps are required for the full enhancement effect remains to be determined. PMID- 1447927 TI - Masking of tinnitus induced by sound. AB - Two experiments were performed in which 8 listeners used external sound to mask the tinnitus induced by a 95-dB SPL tone presented for 1 min. Wider bandwidth noises were more effective maskers than noises of critical bandwidth, which, in turn, were more effective than tonal maskers. Contralateral maskers were often effective, but less so than ipsilateral maskers. Tuning curves showed some degree of frequency specificity that was not related to the frequency of the tinnitus inducing tone. There were consistent and pronounced differences between individual listeners. Overall, our results indicate both similarities and differences between the masking of induced tinnitus and the masking of pathological tinnitus. PMID- 1447928 TI - Discovery and expository methods in teaching visual consonant and word identification. AB - An experiment was conducted to examine the processes involved in lipreading as well as to investigate an optimal approach to teaching lipreading skill. We compared discovery and expository methods of learning to lip-read. Twenty-six college students with normal hearing were trained over 3 days to lip-read consonant-vowel (CV) syllables. The training material consisted of a prerecorded videotape of four different talkers. The task was a forced-choice procedure with feedback. Subjects learned with training, but there was no difference between the two learning methods. As a retention measure, subjects returned 4 weeks later and repeated the training. There were significant savings of the original learning. Three weeks after the retention phase, subjects were tested with a 10-item forced choice monosyllabic word task. Those subjects who had extensive training on CV syllables did no better on identifying the monosyllabic words than did a control group of 9 subjects with no training. Nevertheless, performance for all three groups (discovery, expository, and no training) improved during training in the word identification task. PMID- 1447929 TI - The role of spectral and temporal cues in vowel identification by listeners with impaired hearing. AB - This study examined the use of duration and formant frequency in the labeling of synthetic CVC stimuli forming a beet-bit continuum. Durational and F2 frequency cues to vowel identity varied systematically across stimuli. Subjects with normal hearing tended to rely primarily on F2 frequency in vowel labeling, whereas subjects with impaired hearing relied less on F2 information. This group difference was observed even for stimuli with large F2 differences, which were easily discriminated by all subjects. The effect of vowel duration on labeling was similar for both groups, with long-duration stimuli receiving more "beet" responses than short-duration stimuli across the F2 range. Psychoacoustic measures of frequency resolution and temporal resolution were poor predictors of a subject's use of formant information and duration information in labeling. PMID- 1447930 TI - The identification of affective-prosodic stimuli by left- and right-hemisphere damaged subjects: all errors are not created equal. AB - Impairments in listening tasks that require subjects to match affective-prosodic speech utterances with appropriate facial expressions have been reported after both left- and right-hemisphere damage. In the present study, both left- and right-hemisphere-damaged patients were found to perform poorly compared to a nondamaged control group on a typical affective-prosodic listening task using four emotional types (happy, sad, angry, surprised). To determine if the two brain-damaged groups were exhibiting a similar pattern of performance with respect to their use of acoustic cues, the 16 stimulus utterances were analyzed acoustically, and the results were incorporated into an analysis of the errors made by the patients. A discriminant function analysis using acoustic cues alone indicated that fundamental frequency (FO) variability, mean FO, and syllable durations most successfully distinguished the four emotional sentence types. A similar analysis that incorporated the misclassifications made by the patients revealed that the left-hemisphere-damaged and right-hemisphere-damaged groups were utilizing these acoustic cues differently. The results of this and other studies suggest that rather than being lateralized to a single cerebral hemisphere in a fashion analogous to language, prosodic processes are made up of multiple skills and functions distributed across cerebral systems. PMID- 1447931 TI - Effects of vocal task and respiratory phase on prephonatory chest wall movements. AB - A vocal reaction time paradigm was used to explore prephonatory respiratory kinematics. Movements of the rib cage and abdomen were recorded prior to production of utterances differing in length and intensity, and vocal responses were elicited in different phases and volumes of the quiet breathing cycle. A velocity threshold was used to distinguish prephonatory adjustments from the cyclical movements of the chest wall that are characteristic of quiet breathing. The results suggest that a variety of prephonatory kinematic events can occur prior to initiation of vocalization in response to a stimulus. Further, prephonatory movements appear to be adaptive in that they are influenced by the length of the utterance to be spoken and the respiratory volume at the time of voice initiation. PMID- 1447932 TI - Choosing a treatment procedure for early stuttering: issues and future directions. AB - The new responsibility of speech-language pathologists to provide direct, early intervention for stuttering creates a further responsibility for them to choose justifiable treatment procedures for that intervention. This paper has two purposes. The first is to encourage clinicians to evaluate the conceptual and practical aspects of the treatments they use for early stuttering. The second purpose of the paper is to overview available early intervention procedures and consider the advantages, disadvantages, and prominent issues associated with each. The procedures considered are environment manipulation, prolonged speech, and response-contingent stimulation. It is concluded that clinicians have no cause to be satisfied with any currently available early intervention procedure. Further, it is concluded that (a) although anticipatory struggle theories have made a useful contribution to scholarship, their line of theoretical reasoning is questionable for clinical practice; (b) although theoretically sound for the purpose, variants of prolonged speech pose prohibitive conceptual and practical shortcomings if they are used to treat very young stuttering children; (c) despite its disadvantages, response contingent stimulation is the most conceptually and practically justifiable method for early intervention with stuttering. PMID- 1447933 TI - Reliability of speech naturalness ratings of stuttered speech during treatment. AB - This study evaluated the reliability with which relatively sophisticated and unsophisticated judges used a 9-point scale to rate the speech naturalness of speech samples from 10 clients in a treatment program for stuttering that employed prolonged speech. Judges rated repeated speech samples from different speakers during various phases of the program. Different groups of sophisticated and unsophisticated judges made ratings at either 15 sec, 30 sec, or 60 sec intervals while listening to the samples. Of the reliability indices, intraclass correlations were significantly higher for sophisticated judges although the consistency and agreement of unsophisticated judges were generally equivalent to that of sophisticated judges. Both agreement scores and intraclass correlations were higher when ratings were made at 60 sec rather than 30 sec intervals. The predominant variable that influenced judgement reliability appeared to be differences among the subjects. The methodology partially replicated Martin, Haroldson, and Triden's (1984) initial investigation on the use of this scale. However, the levels of intra- or interjudge reliability in this study were lower than the levels achieved by Martin et al.'s judges. There were important differences between the Martin et al. study and this one that may account for the findings, and these are discussed. PMID- 1447934 TI - [Efficiency of prevaccination screening of anti-HBc in the anti-hepatitis B vaccination programs]. AB - BACKGROUND: The convenience of carrying out pre-vaccination screening of VHB markers depends on the relative costs of screening and vaccination and also on the prevalence of susceptible subjects in each group of the population. The aim of the present work was to analyse the efficiency of pre-vaccination screening of antiHBc in Catalonia in 1991. METHODS: The per-unit cost of screening was calculated at 1366 ptas. The formula applied was: cost per-unit of screening + (1 X) x the cost per-unit of vaccination of anti-HBc (-) = cost of vaccinating the group. "X" being the threshold of prevalence of markers below which screening cases to be efficient. This prevalence is compared with those expected in the groups of the population to be vaccinated. RESULTS: By applying the above-mention ned formula and taking into account costs in time and travel of the people to be vaccinated, a prevalence threshold of 23% is obtained. This prevalence is much higher than that found in adolescents and students of medicine and nursing, similar to that found in health professionals and lower than that of other risk groups. CONCLUSIONS: Systematic screening of anti-HBc is only recommended in groups of the population where a prevalence higher than 20-25% can be expected. Below this threshold vaccination without previous study of markers is more efficient. This enormously simplifies the strategies of universal vaccination of children, adolescents or both. PMID- 1447935 TI - [Prognostic effect of beta 2-microglobulin in multiple myeloma]. AB - BACKGROUND: The aim of the present study was to compare the prognostic influence of beta 2-microglobulin (B2M) corrected according to renal function versus the uncorrected form and relate these values with other characteristics of the disease in a series of patients with multiple myeloma (MM). METHODS: The serum levels of B2M were determined by the radioimmunoassay method (RIA) in 107 patients with newly diagnosed MM and the prognostic influence of B2M was statistically evaluated with univariant and multivariant analysis. RESULTS: The mean value of B2M obtained in patients with MM was 7.8 +/- 8.0 micrograms/ml, with a median of 5 micrograms/ml. Ninety percent of the patients studied presented serum values of B2M higher than the normal limit. The value of B2M corresponding to the median of the series (5 micrograms/ml) separated two groups of patients with different survival (48 vs 19 months) (p = 0.0001). Similarly, the most discriminative value of corrected B2M in agreement with creatinine (2.5 micrograms/ml) permitted the differentiation of two groups of patients although the differences in survival were less significant (36 vs 26 months, p = 0.03) demonstrating its lesser influence as a prognostic factor with respect to the uncorrected B2M. In contrast, a significant association was observed between high values of B2M and Bence Jones myeloma, clinical stage III, anemia, renal failure and intense involvement of the general state. Multivariant analysis demonstrated that B2M plays a greater prognostic role when used as a discrete rather than a continuous variable and that together with the degree of involvement of the general state, serum albumin and the proportion of plasma cells in the bone marrow, they make up the best set of variables for the prediction of prognosis in patients with MM. CONCLUSIONS: Beta 2-microglobulin is one of the most important independent prognostic factors in multiple myeloma with its prognostic value being greatest when used uncorrected according to the values of creatinine. PMID- 1447936 TI - [Is it possible to predict the evolution of HIV infection?]. PMID- 1447937 TI - [Reality and enigmas in left ventricular hypertrophy in arterial hypertension]. PMID- 1447938 TI - [Bronchiolitis obliterans associated with organizing pneumonia. Clinico pathological study of 6 cases]. AB - Over the last three years six patients diagnosed of bronchiolitis obliterans with organizing pneumonia were studied. Diagnosis was established by open lung biopsy in 4 and by transbronchial lung biopsy in 2. The initiation of the symptoms was subacute although one patient evolved to respiratory failure requiring mechanical ventilation. The mean age of presentation was 68 years with male predominance over females of 5:1. The most frequent symptoms were fever and general malaise in 6 patients, cough and dyspnea in 4, respectively and weight loss in 2 patients. Functional respiratory tests showed restrictive ventilation disturbances in 4 out of 5 patients, mixed in 1 and a reduction in diffusion capacity in the 5 patients in whom it was determined. The radiologic pattern of multifocal alveolar infiltration was present in 6 cases. Interstitial involvement was also associated in 3 patients with pleural effusion in 2. Histologic findings of intraluminal polypoid masses affecting the bronchiols and alveolar conducts (bronchiolitis obliterants) with extension to the alveoli forming conjunctive Masson polyps (organizing pneumonia) was found in the 4 patients who underwent open lung biopsy and in 1 diagnosed by transbronchial biopsy although there were quantitative differences in the degree of alveolar involvement. Response to treatment with steroids was favorable in 5 out of 6 patients while the remaining patients spontaneously improved following thoracotomy. PMID- 1447939 TI - [Prostatic cancer: biological aspects of clinical interest]. PMID- 1447940 TI - [Prognostic factors in breast cancer with negative lymph nodes]. PMID- 1447941 TI - [Tophaceous deposit in the fingertips of patients without gouty arthritis]. PMID- 1447942 TI - [Mesangial glomerulonephritis with focal lesions and a polycystic kidney in an adult]. PMID- 1447943 TI - [Respiratory distress and fulminant septic shock, diagnosed by lymph node biopsy in and adult patient with unrecognised HIV infection]. PMID- 1447944 TI - [Brucella abortus meningitis in a patient with HIV infection]. PMID- 1447945 TI - [Therapeutic measures in massive pulmonary thromboembolism]. PMID- 1447946 TI - Inhibition of human T-lymphocyte activation by macrolide antibiotic, roxithromycin. AB - Effects of macrolide antibiotic, roxithromycin (RXM) on human lymphocytes in culture were studied. The drug showed a dose-dependent inhibition of 3H-thymidine and 35S-methionine uptake responding to T cell mitogens and purified protein derivative of tuberculin (PPD). Activation by PPD, as assessed by 3H-thymidine uptake, was more sensitive to inhibition than the response to T cell mitogens. The drug produced a loss of blasts when added soon after transformation commenced. Immunosuppressive effects of RXM were further characterized by using four different types of metabolized RXM, RU 28111, RU 39001, RU 44981 and RU 45179. The most potent inhibitor of lymphocyte transformation was RU 45179, followed by RU 44981, RU 39001 and RU 28111 have little activity. PMID- 1447947 TI - Intracerebroventricular injection of antibodies directed against Gs alpha enhances the supraspinal antinociception induced by morphine, beta-endorphin and clonidine in mice. AB - The intracerebroventricular (i.c.v.) injection of antisera directed against different sequences of Gs alpha to mice enhanced the antinociceptive potency of the opioids morphine, beta h-endorphin-(1-31) and of the alpha 2-agonist clonidine when studied 24 h later in the tail-flick test. The activity of DAGO, DADLE, DPDPE and [D-Ala2]-Deltorphin II remained unchanged after that treatment. Cholera toxin (0.5 microgram/mouse, i.c.v.), agent that impairs the receptor regulation of Gs transducer proteins promoted comparable changes in the supraspinal analgesia induced by these substances. Six days after a single i.c.v. injection (0.5 microgram/mouse) of pertussis toxin the antinociceptive activity of all the opioids and clonidine appeared diminished. It is concluded that opioids and clonidine promote analgesia after binding to receptors functionally coupled to Gi/G(o) proteins, moreover, the activity of morphine, beta-endorphin and clonidine in this test seems to be counteracted by a process involving activation of Gs alpha transducer proteins. PMID- 1447948 TI - Complete dissociation of DOCA-salt hypertension and red cell ion transport alterations. AB - Our previous study revealed major ion transport alterations that resulted in a pronounced elevation of red cell Na+ content in DOCA-salt treated homozygous vasopressin-deficient (DI) Brattleboro rats in which only a moderate increase of systolic blood pressure occurred. In contrast, no changes of red cell Na+ content were observed in heterozygous vasopressin-secreting (non-DI) Brattleboro rats with a severe DOCA-salt hypertension. Using a chronic supplementation of DI rats with an antidiuretic agonist dDAVP (1-desamino-8-D-arginine vasopressin) we did not demonstrate any significant changes of red cell ion transport in dDAVP treated DI rats with a fully developed DOCA-salt hypertension. The absence of ion transport alterations seems to be mainly due to dDAVP-induced correction of altered K+ metabolism seen in DOCA-salt treated DI animals. It can be concluded that DOCA-salt hypertension can develop even without red cell ion transport alterations which are usually caused by cell K+ depletion. PMID- 1447949 TI - The pharmacological differences and similarities between stress- and ethanol induced gastric mucosal damage. AB - Stress- and ethanol-induced gastric mucosal damage are the two commonly used ulcer models in animals. They share some of the similarities but also have differences in the etiology of gastric ulceration. This article reviews the influences of various protective drugs on these two types of gastric damage in rats. Verapamil (a calcium antagonist) or N-ethylmaleimide (a sulfhydryl depletor) prevents cold restraint-, but potentiates ethanol-provoked gastric lesion formation. N-Acetylcysteine (a mucolytic agent) and acetaminophen (an antipyretic analgesic) have the opposite actions. Prostaglandins provide a much better antiulcer effect on ethanol-induced lesions. Cimetidine (a histamine H2 receptor antagonist) prevents only stress-induced mucosal damage. These differences in drug actions indicate that stress and ethanol may have dissimilar ulcerogenic mechanisms in rats. On the other hand, carbenoxolone (a mucus inducer), histamine H1-receptor antagonists, leukotriene inhibitors (FPL 55712 and nordihydroguaiaretic acid) and mast cell stabilizers (like zinc compounds, sodium cromoglycate, FPL 52694 and ketotifen), all protect against gastric mucosal damage by stress or ethanol in rats. However, the role of gastric sulfhydryls in both types of gastric lesions is still controversial. These findings imply that the two types of lesion formation share some of the ulcerogenic mechanisms. This communication attempts to analyze the various findings and to relate them to the etiology of stress and ethanol-induced gastric lesions. It also summarizes the uses, and the antiulcer mechanisms, of the drugs that have been studied utilizing these two animal ulcer models, and suggests their possible implications in man. PMID- 1447950 TI - Non-right sidedness: an association with lower IL-2 production. AB - Using a laterality questionnaire, 138 normal healthy individuals were classified as right-sided and 25 as non-right sided. Interleukin-2 (IL-2) was generated from whole blood obtained from these subjects using mitogen (PHA) stimulation. IL-2 was quantitated in picograms/ml using an enzyme immunoassay (ELISA). Additionally, sera from these subjects were tested for 7 autoantibodies by standard serological methods. As compared to right sided subjects, non-right sided individuals had significantly lower IL-2 production. Non-right sided individuals with autoantibodies had significantly lower IL-2 production than right sided subjects with or without autoantibodies, but did not differ significantly from their non-right sided counterparts without autoantibodies. These data support the increasing evidence for the differential and lateralized regulation of immune functions by the right and left cerebral regions. PMID- 1447951 TI - Kinetic analyses demonstrate that the equilibrium assumption does not apply to [125I]endothelin-1 binding data. AB - The kinetics of [125I]Endothelin-1 ([125I]ET-1) binding were studied using membranes from rat heart, rat lung, rat brain, and porcine vascular smooth muscle at 37 degrees C in 0.05M Tris-HCl buffer (pH = 7.4). The dissociation half-life (t1/2, diss.) for bound [125I]ET-1 was in excess of 30 hours for each tissue studied. Equilibrium-time requirements for proper Scatchard analysis of [125I]ET 1 were also far in excess of 30 hours for each tissue. These data suggest that determination of dissociation constants, Kd, and receptor concentrations, Bmax, by conventional Scatchard analysis is not feasible with [125I]ET-1. Kinetic analyses may provide a more accurate means for determining [125I-ET-1] binding characteristics including Kd and Bmax. PMID- 1447952 TI - A transient rise in plasma beta-endorphin after a traditional 47 degrees C hot spring bath in Kusatsu-spa, Japan. AB - To clarify the mechanism of the intoxicating feeling attained after a traditional 47 degrees C hot-spring bath called 'jikan-yu' in Kusatsu-spa, Japan, we examined the change in plasma levels of beta-endorphin and methionine enkephalin in 7 healthy subjects. The mean sublingual temperature rose from 36.8 degrees C to 38.6 degrees C and the plasma beta-endorphin level from 16.2 pg/ml to 49.5 pg/ml 2 minutes after completing a 3-minute bath in 47 degrees C hot-spring water. However, the plasma methionine enkephalin level was not changed. This feeling of intoxication may be explained by the transient rise in plasma beta-endorphin level. PMID- 1447953 TI - Age and food restriction alter the porphyrin concentration and mRNA levels for 5 aminolevulinate synthase in rat Harderian gland. AB - The effects of age and food restriction on the porphyrin concentration in Harderian glands were studied in male Fisher 344 rats. Harderian gland porphyrin concentrations increased with age; this was statistically significant in 20 month old animals compared with 3 month old animals. Food restriction (by 40%) prevented the age-associated rise in porphyrins; thus, in 20 month old food restricted rats had porphyrin concentrations similar to those found in young animals. In a second experiment, we correlated the age-associated rise in Harderian gland porphyrin concentrations with an increase in mRNA levels for 5 aminolevulinate synthase (ALV-S). Both the porphyrin concentration and ALV-S mRNA rose at 12 and 18 months of age, but decreased by 24 months of age. It is concluded that, a) porphyrin biosynthesis in the Harderian glands increases up to 20 months of age but decreases in rats that are 24 months old, and b) food restriction prevents the porphyrin rise associated with age in the Harderian gland of male Fisher 344 rats. PMID- 1447954 TI - Diagnostic tools from molecular biology. PMID- 1447955 TI - In situ hybridization: optimization of the techniques for collecting and fixing the specimens. AB - An overview is presented concerning the different protocols for collecting and fixing the specimens for in situ hybridization analysis. Particular attention is devoted to the problem of avoiding the tissue RNA degradation due to the ubiquitous and rather resistant RNases. The choice of the final protocol largely depends on a compromise between the need to maintain morphological details, the care to avoid loss of the target nucleic acids and the capability of the probe to diffuse within the specimen. PMID- 1447956 TI - Autoradiographic detection of radiolabelled probes by in situ hybridization. AB - In the context of in situ hybridization techniques, autoradiography is used to localize radiolabelled probes within intact tissue sections or cell preparations. The present report describes in detail a standardized autoradiographic procedure. Topics include the choice of the emulsion, its preparation and layering onto the slides, the development procedure and the analysis of the results. Special attention is devoted to the practical aspects, so that the technique will be generally applicable, according to the reader's needs. PMID- 1447957 TI - Non-radioactive nucleic acid probes: labelling and detection procedures. AB - A comprehensive overview is given concerning the in situ hybridization techniques using non-radioactively labelled probes. Details are given on the preparation of the probes with different reporter molecules and on the corresponding revealing assays. The development of non-isotopic labelling methods for nucleic acid probes has facilitated the diffusion of the in situ hybridization techniques to the research as well as to the clinical pathology laboratory. Non-radioactive probes have several advantages over the radiolabelled ones, including cost, shelf-life, safety and, last but not least, resolution of the signal. PMID- 1447958 TI - Use of sulphonated probes for detecting human immunodeficiency virus-1 transcripts by in situ hybridization. AB - A detailed procedure is described that allows detection of the presence of human immunodeficiency virus-1 (HIV-1) transcripts within both acetone-fixed tissues and peripheral blood mononuclear cells. This assay uses cDNA probes labelled by a non-isotopic procedure that results in the modification of cytosine residues through covalent linkage to a sulphone group. In situ hybridized probe is then detected by an alkaline phosphatase-conjugated antibody specifically directed against the sulphone hapten. This procedure is specific, rapid and safe and can be applied in the research as well as in the clinical pathology settings. PMID- 1447959 TI - From two dimensional (2D) to three dimensional (3D) analysis by confocal microscopy. AB - The confocal microscope is becoming increasingly important as an apparatus to analyze the 3-D topography of the cell. Main reasons are the high resolution optical sectioning capacity, the non-invasiveness which leaves the object intact, and the imaging capabilities. This chapter introduces a description of the confocal principle, the basic concepts of confocal fluorescence microscopy and some criteria for cell preservation. Optimization of in situ immunofluorescence, hybridization and detection procedures in combination with new digital microscope techniques can fully express their capacities only if the preparation of biological specimens is accurate for 3-D analysis. Some applications of confocal microscopy to the study of intranucleolar antigens, enzyme translocations and fluorescence in situ hybridization, are described in association with 3-D software image processing, as a useful framework for the study of the 3-D visualization of proteins and chromatin domains. PMID- 1447960 TI - Localization of cloned human DNA sequences and analysis of chromosomal alterations by in situ hybridization. AB - The in situ hybridization technique was used for the localization on human chromosomes of single-copy and repeated sequences and, in addition, for the characterization of altered human chromosomes. Two anonymous clones, single or low-copy, obtained from a human X chromosome library were localized on the distal part of the long arm and in the paracentromeric region of X chromosome, respectively. A genomic fragment of the single-copy thyroglobulin (TG) gene was used to confirm the localization on the distal part of the long arm of chromosome 8. The localization and distribution on human chromosomes of the glyceraldehyde-3 phosphate dehydrogenase (GAPD) multigene family obtained by in situ hybridization and by somatic cell hybrids were compared. A phosphoglycerate kinase (PGK) c-DNA clone, which detects genic and pseudogenic sequences on the X chromosome, was used for the characterization of three small ring markers present in unrelated female patients. PMID- 1447961 TI - From immunohistochemistry to in situ hybridization. AB - The revolutionary evolution in science and technology has made it possible to face adequately three main challenges in modern medicine: old diseases changing, new diseases appearing, diseases remaining unknown. In this paper we review the road travelled by the pathologist in search of a method which is based upon the application to routine work of instruments and techniques which once were available for research only. Application to tissue studies of immunological and molecular biology techniques allows a dynamic interpretation of biological phenomena with special regard to gene regulation and expression. The method implies stepwise investigations, including immunohistochemistry, EM and in situ hybridization, in order to progress from the suggestive features detectable in routinely stained preparations to more characteristic, specific and, finally, pathognomonic features. HE-stained preparations and appropriate immunohistochemical stains enable recognition of phenotypic changes which may reflect genotypic alterations. Thus there is a logical and methodological link between the simple HE and the most powerful techniques so far introduced in pathology: immunohistochemistry and in situ hybridization. PMID- 1447962 TI - Genetic variants of alpha-1-antitrypsin (AAT). AB - This paper reviews the genetic variants of alpha-1-antitrypsin (AAT) which have been sequenced with special emphasis on the s.c. deficiency variants. These result in AAT low plasma levels via three main mechanisms: 1) intracellular storage; 2) intracellular degradation; 3) lack of synthesis. Intracellular storage occurs with the classical Z variant and with a few variants called M like, because of their isoelectric focusing (IF) pattern. The storage phenomenon causes liver damage and can be demonstrated at both light and electron microscopic level with the help of immunohistochemistry. We report a new deficiency variant of AAT (M-Cagliari) characterized by very low plasma levels, massive storage of AAT and liver cirrhosis. By using immunohistochemical techniques and DNA analysis we could demonstrate that M-Cagliari has antigenic and genetic properties other than the Z AAT. PMID- 1447963 TI - Breakdown of mucosal defences in congestive gastropathy in cirrhotics. AB - The gastric mucus-bicarbonate barrier, the first line of mucosal defence, has been evaluated in patients with congestive gastropathy and cirrhosis of the liver. Fourteen cirrhotic patients of both sexes (Child's class A or B), with or without oesophageal varices, but with endoscopic signs of congestive gastropathy, and a matched group of healthy controls were studied. The amount of luminal mucoproteins, a Mucoprotective Index as a qualitative assessment of mucus secretion and the output of gastric bicarbonate were determined in basal conditions. In patients with congestive gastropathy a significant (p < 0.01) reduction in all the above parameters was observed, suggesting a substantial impairment of the gastric mucus-bicarbonate barrier. Whether this is an independent phenomenon or a consequence of altered local microcirculation remains to be determined. PMID- 1447964 TI - Role of the spleen in endotoxin-induced hepatic injury in chronic alcohol-fed rats. AB - The present experiments were designed to study the role of the spleen in endotoxin-induced hepatic injury in chronic alcohol-fed rats. Administration of 2 mg/kg body weight of endotoxin caused severe hepatic injury in chronic alcohol fed rats as compared with controls. This injury was significantly less in those whose spleens had been resected 1 week prior to endotoxin administration. There were no differences in plasma endotoxin levels 16 h after intravenous injection of endotoxin between sham-operated control rats, and chronic alcohol-fed rats with and without splenectomy. The plasma tumor necrosis factor (TNF) level 1 h after intravenous injection of endotoxin was significantly higher in chronic alcohol-fed rats than in controls. However, TNF levels were significantly lower in those with splenectomy. Neutrophil infiltration was seen in the liver sinusoid of sham-operated chronic alcohol-fed rats as early as 1 h after injection of endotoxin, and was observed even 15 h later. These results suggest that endotoxin induced liver injury is closely related to factors derived from the spleen and induced by plasma endotoxin, especially when Kupffer cell function is reduced by chronic alcohol feeding. In addition, TNF and neutrophils may play an important role in this type of liver injury. PMID- 1447965 TI - Liver function after bilateral nephrectomy. AB - Consequences of bilateral nephrectomy (NX) for liver functions and for hepatic excretion of various endogenous substances were characterized in rats 24 h after NX. Plasma concentrations of urea, creatinine, fibrinogen, and glutathione increased significantly after NX, whereas the concentrations of total protein, albumin, and lipids decreased. The hepatic excretion of urea, creatinine, phospholipids, cholesterol, and aldosterone significantly increased in uremia, and excretions of protein and glutathione diminished. Active biliary transport can be diminished after NX by the effects of uremic toxins on the liver cells or by the competition phenomena between endogenous substances, which are normally excreted in urine, at the hepatocellular level. Reduced glutathione content and increased lipid peroxidation in hepatocytes have been found. Changes in lipid and protein metabolism after NX can be proved. PMID- 1447966 TI - Decreased hepatic uptake of cholesterol and retinol in the dimethylnitrosamine rat model of cirrhosis. AB - The fenestrated endothelium of the liver sinusoids forms a sieve between the circulation and hepatocytes. Fenestrae selectively permit the entrance of relatively small chylomicron remnants into the space of Disse to contact hepatocyte receptors, but obstruct the passage of the larger parent chylomicrons. Much of dietary cholesterol and most of retinol are transported as esters in the core of chylomicrons. In the dimethyl nitrosamine rat model of cirrhosis, we have described a rapid reduction in size and number of fenestrae well before the onset of cirrhosis. Concurrent with this decreased porosity is a decreased trapping of radio-labelled dietary cholesterol and retinol by these livers. We postulate that the less porous "liver sieve" hinders the hepatic uptake of chylomicron remnants, with consequent disturbance of cholesterol and retinol metabolism. PMID- 1447967 TI - Immunoquantification of cytochrome P-450 3A on rat paraffin-embedded liver tissue. AB - The cytochrome P-450 3A family is involved in the metabolism of several drugs, including nifedipine, cyclosporine, quinidine and erythromycin. The purpose of this study was to develop a reliable method to obtain a relative quantification of cytochrome P-450 3A apoproteins in rat liver specimens by immunocytochemistry and to correlate such quantification to erythromycin N-demethylase activity, a biochemical pathway sustained by that enzymatic system. Thirty-six male Wistar rats were treated with an injection of either saline or dexamethasone phosphate (10, 30 or 50 mg/kg), a potent inducer of cytochrome P-450 3A. Specimens taken from the same lobe were processed for immunocytochemistry and determination of erythromycin N-demethylase activity. Paraffin sections were treated with a polyclonal antiserum directed against cytochrome P-450 3A. The density of cytochrome P-450 3A immunostaining measured by an automatic image analyzer increased with the dose of dexamethasone pretreatment, and with the erythromycin N-demethylase activity, both parameters being closely correlated. Our data indicate that in rats, when cytochrome P-450 3A is concerned, there is a close correlation between the results of immunoquantitation and biochemical activity. This suggests that such a method of investigation might be used on small paraffin embedded liver specimens obtained by needle biopsy. PMID- 1447968 TI - Immunoperoxidase localization of ursodeoxycholic acid in rat biliary epithelial cells. Evidence for a cholehepatic circulation. AB - To explain the hypercholeretic effect of ursodeoxycholic acid, a cholehepatic shunt circulation has been postulated. This pathway includes secretion by the hepatocyte into bile and absorption by the biliary epithelial cells. To test this possibility, we have attempted to localize ursodeoxycholic acid in hepatocytes and portal bile duct cells by an indirect immunoperoxidase technique using specific polyclonal antibodies against ursodeoxycholic acid and cholic acid conjugates. Rat livers were fixed with paraformaldehyde, incubated with antibodies directed against bile acids and examined by electron microscopy. After infusion of ursodeoxycholic acid and incubation with antibodies against this bile acid, an electron-dense staining was observed on the apical (luminal) membrane of the portal bile ductal cells. In contrast, no staining was observed when no ursodeoxycholic acid was infused, or after infusion with taurocholate and incubation with antibodies against cholic acid conjugates. These observations are consistent with absorption of ursodeoxycholic acid by the portal bile ducts and a cholehepatic circulation of this bile acid. PMID- 1447969 TI - The role of integration host factor in gene expression in Escherichia coli. AB - Integration host factor is a sequence-specific, histone-like, multifunctional DNA binding and -bending protein of Escherichia coli. The characterization and functional analysis of this protein has been done mainly in bacteriophage lambda and other mobile genetic elements. Less is known concerning the role of integration host factor (IHF) in E. coli, although it has been implicated in a number of processes in this organism including DNA replication, site-specific recombination, and gene expression. This review presents recent work which suggests that IHF alters the activity of an unusually large number of operons in E. coli. We discuss the possible physiological relevance of the involvement of IHF in gene expression and the hypothesis that IHF is a member of a class of functionally redundant proteins that participate in chromosome structure and multiple processes involving DNA. PMID- 1447970 TI - Septal membrane fusion--a pivotal event in bacterial spore formation? AB - Formation of the asymmetrically located septum divides sporulating bacilli into two distinct cells: the mother cell and the prespore. The rigidifying wall material in the septum is subsequently removed by autolysis. Examination of published electron micrographs indicates that the two septal membranes then fuse to form a single membrane. Membrane fusion would be expected to have profound consequences for subsequent development. For example, it is suggested that fusion activates processing of pro-sigma E to sigma E in the cytoplasm by exposing it to a membrane-bound processing enzyme. Asymmetry of the fused membrane could restrict processing to one face of the membrane and hence explain why sigma E is associated with transcription in the mother cell but not in the prespore. Asymmetry of the fused membrane might also provide a mechanism for restricting the activity of another factor, sigma F, to the prespore. Attachment of the flexible fused septal membrane to the condensing prespore nucleoid could help drive the engulfment of the prespore by the mother cell. PMID- 1447971 TI - Expression of a functional neisserial fbp gene in Escherichia coli. AB - The ability to acquire iron from a human host is a major determinant in the pathogenesis of Neisseria gonorrhoeae and Neisseria meningitidis. Pathogenic Neisseria spp. do not synthesize siderophores and instead express a receptor mediated, high-affinity iron acquisition system in the iron-restricted environment of its host. A ferric-iron-binding protein (Fbp) of Neisseria spp. is also iron-regulated and may play a central role in this novel iron-uptake system. To define the physical properties of Fbp further, we used polymerase chain reaction to synthesize DNA fragments containing the fbp structural gene with and without the sequence encoding the Fbp leader peptide. These fragments were ligated into pUC13 to create in-frame fusions with the alpha peptide of lacZ. The expression of Fbp was under the control of the lacZ promoter. Both fusion clones produced Fbp in large amounts, facilitating the purification of quantities of Fbp sufficient for elucidating the biochemical, immunologic, and functional properties of this protein. PMID- 1447972 TI - Control of gene expression in the temperate coliphage 186. IX. B is the sole phage function needed to activate transcription of the phage late genes. AB - Using plasmid clones we have determined that the late control function B is the only phage function that is needed to activate a late promoter of coliphage 186, and we predict that it functions as an auxiliary factor to RNA polymerase in the activation of late transcription. We have also shown that a high concentration of B will activate late transcription from a prophage, and we conclude that replicating DNA is not a template requirement for B to function. The original demonstration of a need for the replication gene A in late transcription can be explained by the fact that replication leads to an increase in B gene dosage, with the consequent increase in B concentration leading to the efficient activation of the late promoters. PMID- 1447973 TI - Control of gene expression in the temperate coliphage 186. X. The cI repressor directly represses transcription of the late control gene B. AB - We have found that the repressor of 186 lytic transcription, CI, represses transcription of the late control gene B, with no involvement of the B protein itself. In clone studies we showed that CI repressed transcription from the B promoter and that temperature inactivation of CIts led to B derepression. We conclude that CI repressor directly represses transcription of the B gene and, with prophage induction, it is probable that the inactivation of the CI repressor not only derepresses early lytic transcription, but also derepresses B gene transcription, leading to the activation of transcription from the late promoters. PMID- 1447974 TI - Expression of bacterial cytotoxin genes in mammalian target cells. AB - We have studied the expression of the gene fragments encoding the enzymatically active portion of three bacterial cytotoxins: exotoxin A (ETA) of Pseudomonas aeruginosa, and pertussis toxin (PT) and adenylate cyclase toxin (CYA) of Bordetella pertussis, in sensitive mammalian target cells. Expression of active ETA and CYA was lethal to the producing cells and stable transfectants of Cos-1 cells containing the corresponding genes could not be obtained. The expression of the PTS1 subunit was tolerated by the producing mammalian cells. Since PT is cytotoxic because of ADP-ribosylation of G-proteins, we assume that the endogenously expressed PTS1 may not find the cellular target G proteins or PTS1 alone may not be sufficient for ADP-ribosylation of these proteins in vivo. PMID- 1447975 TI - Identification and sequence of a Na(+)-linked gene from the marine bacterium Alteromonas haloplanktis which functionally complements the dagA gene of Escherichia coli. AB - A 4.0 kb fragment from a plasmid genomic DNA library of the marine bacterium Alteromonas haloplanktis ATCC 19855 was found in the presence of Na+ to complement the dagA gene of Escherichia coli. We have completely sequenced this fragment and the position of the Na(+)-linked D-alanine glycine permease gene (dagA) on the fragment has been determined by complementation. The predicted carrier protein consists of 542 amino acid residues (M(r) 58,955). Its hydropathy profile suggests it is composed of eight transmembrane segments with a long hydrophilic region between segments six and seven. Significant similarity has been found between this Na(+)-linked permease and the Na+/proline permeases of E. coli and Salmonella typhimurium and the human and rabbit intestinal Na+/glucose cotransporters. PMID- 1447976 TI - Conservation of the photosynthesis gene cluster in Rhodospirillum centenum. AB - Intraspecies and intergenus complementation analysis were utilized to demonstrate that photosynthesis genes are clustered in distantly related purple photosynthetic bacteria. Specifically, we show that the linkage order for genes involved in bacteriochlorophyll and carotenoid biosynthesis in Rhodospirillum centenum are arranged essentially as in Rhodobacter capsulatus and Rhodobacter sphaeroides. In addition, the location and relative distance observed between the puf and puh operons which encode for light harvesting and reaction-centre structural genes are also conserved between these species. Conservation of the photosynthesis gene cluster implies either that there are structural or regulatory constraints that limit rearrangement of the photosynthesis gene cluster or that there may have been lateral transfer of the photosynthesis gene cluster among different species of phototrophic bacteria. PMID- 1447977 TI - Loss of the pigmentation phenotype in Yersinia pestis is due to the spontaneous deletion of 102 kb of chromosomal DNA which is flanked by a repetitive element. AB - The pigmentation (Pgm+) phenotype of Yersinia pestis encompasses a variety of different physiological traits, all of which are missing in Pgm- mutants. We have previously shown that loss of the Pgm+ phenotype is accompanied by the spontaneous deletion of at least 45 kb of chromosomal DNA, referred to as the pgm locus. Using chromosomal walking, we have now mapped the full extent of the pgm locus in Y. pestis strain KIM6+. Our results indicate that the locus spans 102 kb of DNA which is absent in the spontaneous Pgm- mutant, KIM6. Yersinia pseudotuberculosis PB1/0 contains sequences homologous to the entire pgm locus while only part of this region hybridized to Yersinia enterocolitica WA-LOX DNA. Restriction enzyme mapping and hybridization studies revealed the presence of a repetitive element at both ends of the pgm locus and in multiple copies elsewhere in the Y. pestis genome. This element may be responsible for generating the deletion. PMID- 1447978 TI - flhF, a Bacillus subtilis flagellar gene that encodes a putative GTP-binding protein. AB - We describe the sequence and characterization of the Bacillus subtilis flhF gene. flhF encodes a basic polypeptide of 41 kDa that contains a putative GTP-binding motif. The sequence of FlhF reveals a structural relationship to two Escherichia coli proteins, Ffh and FtsY, as well as to other members of the SRP54 family, in a domain presumed to bind GTP. flhF is located in a large operon consisting of chemotaxis and flagellar genes. Cells deficient in flhF are nonmotile. Through the use of anti-flagellar antibodies we have established that flhF is a flagellar (fla) gene. Thus, flhF is a unique flagellar gene in that it encodes a GTP binding protein with similarities to members of the SRP54 family of proteins. These data suggest that flagellar biosynthesis in B. subtilis requires GTP. PMID- 1447979 TI - Identification and characterization of FliY, a novel component of the Bacillus subtilis flagellar switch complex. AB - The Bacillus subtilis gene encoding FliY has been cloned and sequenced. The gene encodes a 379-amino-acid protein with a predicted molecular mass of 41,054 daltons. FliY is partly homologous to the Escherichia coli and Salmonella typhimurium switch proteins FliM and FliN. The N-terminus of FliY has 33% identity with the first 122 amino acids of FliM, whereas the C-terminus of FliY has 52% identity with the last 30 amino acids of FliN. The middle 60% of FliY is not significantly homologous to either of the proteins. A fliY::cat null mutant has no flagella. Motility can be restored to the mutant by expression of fliY from a plasmid, although chemotaxis is still defective since the strain exhibits smooth swimming behaviour. fliY::cat is in the cheD complementation group. One of the cheD point mutants does not switch although the population grown from a single cell has both smooth swimming and tumbling bacteria, implying that the switch is locked. Expression of fliY in wild-type B. subtilis makes the cells more smooth-swimming but does not appear to affect chemotaxis. Expression of fliY in wild-type S. typhimurium severely inhibits chemotaxis and also makes the cells smooth swimming. Expression in a non-motile S. typhimurium fliN mutant restores motility but not chemotaxis, although expression in a non-motile E. coli fliM mutant does not restore motility. The homology, multiple phenotypes, and interspecies complementation suggest that FliY forms part of the B. subtilis switch complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1447980 TI - gltF, a member of the gltBDF operon of Escherichia coli, is involved in nitrogen regulated gene expression. AB - We report here the construction and analysis of insertional mutations in each of the three genes of the gltBDF operon and the nucleotide sequence of the region downstream from gltD. Two open reading frames were identified, the first of which corresponds to gltF. The gltB and gltD genes code for the large and small subunits, respectively, of the enzyme glutamate synthase (GOGAT). gltF codes for a protein, with a molecular mass of 26,350 Da, which is required for Ntr induction. Histidase synthesis was determined as a measure of Ntr function. First, insertions in gltB, gltD or gltF all prevent Ntr induction. Second, complementation analysis indicates that high-level expression of both the gltD and gltF genes is required for the induction of the Ntr enzymes under nitrogen limiting conditions, indicating that the phenotype of the gltB insertion probably results from polarity on gltD and gltF. Third, glutamate-dependent repression of the glt operon appears to be mediated by the product of the gltF gene. Thus, the gltBDF operon of Escherichia coli is involved in induction of the so-called Ntr enzymes in response to nitrogen deprivation, as well as in glutamate biosynthesis. PMID- 1447981 TI - Four homologous domains in the primary structure of GrsB are related to domains in a superfamily of adenylate-forming enzymes. PMID- 1447982 TI - Calcitriol and postmenopausal osteoporosis. PMID- 1447983 TI - Dyspepsia. PMID- 1447984 TI - Interstate differences in incidence and mortality from melanoma. A re-examination of the latitudinal gradient. AB - OBJECTIVE: To investigate the patterns of cutaneous malignant melanoma (CMM) mortality in Australia. DESIGN: A descriptive analysis of melanoma incidence and mortality in Australia supplemented by a case series analysis of melanoma survival. Melanoma mortality rates were based on tabulations supplied by the Australian Bureau of Statistics for the years 1969-1989. Melanoma incidence rates were based on State cancer registry records for the years 1977-1990. The case series survival analysis was based on detailed individual records from the population-based cancer registries in Tasmania and South Australia. MAIN OUTCOME MEASURES: The level of and rise in melanoma mortality rates during 1969-1989 in Australia; the five-year survival rates for Tasmanian and South Australian cases; and male:female incidence ratios related to latitude. RESULTS: We found annual increases in melanoma mortality rates of 2.5% in men (P < 0.0001) and 1.1% in women (P < 0.0001) for all Australia. The five-year survival rates (with 95% confidence intervals [CI]) were: 67% (59%-75%) for Tasmanian men; 79% (76%-83%) for South Australian men; 80% (74%-86%) for Tasmanian women and 88% (86%-91%) for South Australian women. A change in the male:female incidence ratio with latitude was also found--women have significantly higher incidence rates at higher latitudes, but similar rates to men at lower latitudes. CONCLUSIONS: The age standardised mortality from CMM for the period 1969 to 1989 shows little variation by State for women, despite a considerable range in latitude. CMM mortality in men is increasing at a faster rate than that in women. Between 1982 and 1987 the male:female incidence ratio in high latitudes in the Southern Hemisphere showed an excess of cases in women, a finding which we believe has not been reported before. PMID- 1447985 TI - The treatment of gynaecological malignancy in a general public hospital. AB - OBJECTIVE: To assess the adequacy of treatment of gynaecological cancer in a public hospital and to determine the influence of referral patterns on patient outcome. DESIGN: A retrospective analysis of clinical histories. SETTING: A tertiary-level general public hospital. PATIENTS: 89 patients admitted between 1 January 1979 and 31 December 1987 for primary treatment of a gynaecological malignancy. MAIN OUTCOME MEASURES: The primary study parameter was patient survival. During data analysis, the study parameters were altered to include the adequacy of initial surgery and survival time in relation to the involvement of the Gynaecology Unit. RESULTS: Initial presenting symptoms had a major influence on the referral patterns of patients with a gynaecological malignancy. All patients who presented with abnormal vaginal bleeding were managed by the Gynaecology Unit. Patients with ovarian cancer who presented with non-specific abdominal symptoms and ascites were often managed by other units. There was a statistically significant difference in the adequacy of initial surgery depending on whether the patient was managed by the Gynaecology or the Surgical Unit (P < 0.05). The median survival time of patients managed by the Gynaecology Unit was 20 months; this was considerably longer than the figure of 14 months for other units (P < 0.05). CONCLUSIONS: Patients with ovarian cancer who are managed by a specialised gynaecology unit are more likely to have adequate initial surgery and a longer median survival time. Female patients presenting with non-specific abdominal symptoms, ascites and other signs of intra-abdominal malignancy should be reviewed by a gynaecology unit before initial surgery. PMID- 1447986 TI - General practitioners' attitudes to computer-generated surgical discharge letters. Members of the Department of General Surgery, Fremantle Hospital. AB - OBJECTIVE: To assess general practitioners' attitudes to a computed-generated general surgical discharge letter. To identify the six most important items of information in an ideal discharge letter. DESIGN: One hundred and thirty general practitioners who had received at least six computer-generated surgical discharge letters in one year were circulated with a questionnaire. RESULTS: Most general practitioners approved of the computer-generated discharge letter which included all six of the most important items of information they requested. Eighty-four per cent wished to see a similar computer-generated discharge system extended into other areas of hospital practice. PMID- 1447987 TI - Hepatotoxicity from paracetamol self-poisoning in western Sydney: a continuing challenge. AB - OBJECTIVE: To determine the annual incidence of admissions for paracetamol overdosage in the years 1985 to 1990, morbidity and mortality rates, predictors of poor prognosis and the most appropriate use of N-acetylcysteine (NAC). DESIGN: A retrospective review of case records of all patients with a discharge diagnosis of paracetamol overdosage. SETTING: A 900-bed tertiary referral teaching hospital in western Sydney with a busy accident and emergency department. PATIENTS: 306 patient records were reviewed and details of the overdose and admission were recorded. INTERVENTIONS: NAC infusion in patients with possible paracetamol hepatotoxicity. MAIN OUTCOME MEASURES: Blood paracetamol levels; elevated alanine aminotransferase levels; prolonged prothrombin time; severe liver injury; and NAC side effects. RESULTS: Annual admission rate was constant at circa 55 per annum. Female to male ratio was 2:1. Predictors of liver injury included paracetamol dose over 10 g, presentation more than 10 hours after the overdose and chronic ingestion of more than 80 g alcohol per day. There were no deaths. Fifty-five patients (18%) had toxic paracetamol levels, 51% received treatment with NAC, including 40% of those with non-toxic levels, and 11% of those treated with NAC experienced side effects. CONCLUSION: Paracetamol overdosage continues to be a significant cause of hospital admissions in western Sydney. Severe hepatic damage occurs infrequently and the prognosis for liver injury, when it occurs, is good. Treatment with NAC should be reserved for patients with definite indications for the drug. PMID- 1447988 TI - Motility-like dyspepsia. Current concepts in pathogenesis, investigation and management. AB - Motility-like dyspepsia, a clinical subgroup of functional dyspepsia, refers to the cluster of symptoms which suggests an underlying motility disturbance of the upper gut. Characteristic symptoms, in addition to upper abdominal pain or discomfort, are nausea, vomiting, early satiety, anorexia, postprandial abdominal bloating and excessive repetitive postprandial belching. Patients with concomitant symptoms of irritable bowel syndrome are currently excluded from this clinical entity. Delayed gastric emptying of solids and/or liquids, postprandial antral hypomotility and antroduodenal incoordination, gastric myoelectrical arrhythmias and dysfunction of visceral afferents are the major alterations in upper gut sensorimotor activity which have been described. An empirical trial of medical therapy is warranted if there are no "alarm" symptoms at presentation. If symptoms are not relieved after 2-4 weeks, then investigations of the upper gastrointestinal tract, preferably by endoscopy, to exclude the presence of organic disease, is advisable. Management approaches are then reassurance, dietary manipulations and attention to psychosocial aspects. Prokinetic agents appear to be useful as short-term medical therapy in some patients, but optimum long-term treatment strategies, including the use of medications which may improve a diminished tolerance to gut distension, are not established. PMID- 1447989 TI - How to read a journal article. PMID- 1447990 TI - Lifestyle counselling in general practice. Waste of time or challenge of skill? PMID- 1447991 TI - Pitfalls in penetrating eye injuries. PMID- 1447992 TI - Hearing loss in the elderly. A survey in general practice. AB - OBJECTIVE: To determine the prevalence of undiagnosed hearing impairment in people aged 60 years or over in a general practice setting. DESIGN: A self administered questionnaire followed by physical examination and audiometry. SETTING: A group general practice in the Melbourne suburb of Moorabbin. PATIENTS: Two hundred and one people aged 60 years or over who were not known to be hearing impaired. OUTCOME MEASURE: Results of air-conduction audiometry. RESULTS: Seventy five of the 201 people had undiagnosed hearing loss (37%). The assessments of hearing ability by the patients and their relations were good predictors of the outcome of the audiogram (P < 0.001). Occupational history, medical history and physical examination were poor predictors (P > 0.05). CONCLUSIONS: The use of audiometry for screening for hearing impairment in older general practice patients is likely to have a high yield. A large proportion of people with abnormal audiograms will, however, refuse a hearing aid. PMID- 1447993 TI - Transplantation of the cornea. AB - Corneal transplantation is the most widely practised form of allografting in clinical practice. The operation is used to correct developmental abnormalities of corneal shape such as keratoconus, to overcome opacities of the cornea, to relieve pain and to mend perforations. Corneal transplantation is generally successful but contrary to popular belief, corneal grafts can be rejected. This is a particular problem for patients treated for the sequelae of inflammatory disease. The relative importance of measures such as systemic immunosuppression and tissue typing is less in corneal transplantation than in other forms of clinical allografting. Overcoming rejection, achieving the best optical configuration in a graft, and increasing the number of donor corneas available for transplantation represent the main avenues for achieving improvements in corneal transplantation. PMID- 1447994 TI - Bone marrow transplantation. AB - Over the last 20 years allogeneic bone marrow transplantation from an HLA identical sibling donor has become the treatment of choice for a number of human haematological malignancies, severe aplastic anaemia, some congenital diseases of the immune and haemopoietic systems, and some inborn errors of metabolism. Recently, the successful introduction of HLA-matched unrelated donor transplants, convenient T cell depletion technology, combination immunosuppressive therapy to minimise graft-versus-host disease, blood products that are seronegative for cytomegalovirus, effective antiviral agents, and cloned haemopoietic and immune system growth factors have markedly increased the scope of bone marrow transplantation. Additionally, autologous transplantation appears to have promise especially in lymphoma and breast cancer. PMID- 1447995 TI - Guide to the assessment of percentage "impairment" of the back, neck and pelvis. Australasian College of Rehabilitation Medicine. PMID- 1447996 TI - Identification of infection of an Australian resident with the human immunodeficiency virus type 2 (HIV-2). AB - OBJECTIVE: To present the first confirmed case of human immunodeficiency virus infection type 2 (HIV-2) in an Australian resident. CLINICAL FEATURES: HIV-2 infection in a west African man resident in Sydney was diagnosed in 1992 at Westmead Hospital, Sydney, by serological testing. He was asymptomatic and the blood CD4 T-lymphocyte concentration was not significantly reduced. Infection was probably acquired before migration to Australia. The patient was initially tested for HIV-1 antibody as part of an application for permanent residency. He was in no obvious risk group or transmission category. His serum was repeatedly positive by Genetic Systems enzyme immunoassay (EIA) and borderline by Abbott EIA, was reactive to the HIV-2 peptide on a synthetic envelope peptide assay, and was strongly reactive to all HIV-2 specific viral protein bands on an HIV-2 western blot test. HIV-2 was isolated by co-cultivation of the patient's peripheral blood mononuclear cells and identified by hybridisation using HIV-2 specific oligonucleotide probes, with further confirmation by polymerase chain reaction. INTERVENTION AND OUTCOME: The patient was counselled regarding the clinical course and prognosis of HIV-2 infection, the possible indications for zidovudine therapy, modes of transmission of the virus and safer sex precautions. CONCLUSIONS: This is the first documented case of HIV-2 infection diagnosed in Australia and raises the possibility of other undetected cases. The cost effectiveness of general testing for HIV-2 needs to be assessed and formal epidemiological sentinel programs should be established to monitor specific Australian populations. PMID- 1447997 TI - Epidural injection of depot corticosteroids. Australian Pain Society Limited. AB - This position statement is for general information and discussion only and is not intended as medical advice. Its purpose is to review the current literature on a controversial subject so as to assist medical practitioners who have an interest in pain management. The epidural injection of depot corticosteroids is one of a number of treatment techniques for chronic pain, and it is the view of the directors of the Australian Pain Society Limited that patients with chronic pain require assessment and treatment within multidisciplinary pain management programs. This statement does not encourage or discourage medical practitioners from using epidural steroid injections as a treatment modality. While this review of the pertinent literature may be of assistance to practitioners, no responsibility can be accepted by the Australian Pain Society Limited, or its directors, for any inaccuracy contained in studies referred to therein. All liability is expressly disclaimed for any loss or damage which may arise from any person acting on any statement or information contained herein. PMID- 1447998 TI - The cochlear implant and the deaf community. PMID- 1447999 TI - Change "DNR" to "GPC". PMID- 1448000 TI - Folate supplementation. PMID- 1448001 TI - Sudden death associated with 5-fluorouracil administration. PMID- 1448002 TI - The present status of psychosurgery in Australia and New Zealand. PMID- 1448003 TI - Chloroquine-resistant Plasmodium vivax: it may be a common problem. PMID- 1448004 TI - Asthma morbidity in Australia. PMID- 1448005 TI - In search of the pathogenesis of the refractory cervicobrachial pain syndrome. PMID- 1448007 TI - Air quality on long flights. PMID- 1448006 TI - Psychoactive drug prescribing in the Tasmanian community. PMID- 1448008 TI - The need for a randomised trial of hormone replacement therapy in women with breast cancer. PMID- 1448009 TI - Whiplash in Australia: illness or injury? PMID- 1448010 TI - Whiplash in Australia: illness or injury? PMID- 1448012 TI - HIV infection, confidentiality and discrimination. PMID- 1448011 TI - Non-prescription use of bronchodilator aerosols. PMID- 1448013 TI - HIV infection, confidentiality and discrimination. PMID- 1448014 TI - Licensure of "new generation" conjugated Haemophilus influenzae type b vaccines. PMID- 1448015 TI - A hand burn from unmarked hydrofluoric acid. PMID- 1448016 TI - General practice as a scientific discipline. PMID- 1448017 TI - Cheap thrills. PMID- 1448018 TI - Iron deficiency. PMID- 1448019 TI - Choice of contraceptives. PMID- 1448020 TI - Expert to novice. PMID- 1448021 TI - What is nursing ethics? AB - This article tries to bring some clarity into the current confusion about the nature of nursing ethics. It distinguishes between the empirical, prescriptive and analytic dimensions of ethics. It then describes six contemporary understandings of the parameters and aims of ethics via six different approaches: moral education, management, professional conduct, bioethics, clinical ethics and political ethics. PMID- 1448022 TI - Swedish nursing instructors' views of nursing. AB - The views of Swedish nursing instructors of the concept of nursing are examined. The approach is an inductive one based on grounded theory, which is derived from phenomenology and sociological field research methods. The data were collected by selective sampling and by interviewing 14 teachers in two nursing schools (one small and one large) in Sweden. The analysis shows that the core of nursing can be described as helping the patients either to manage their daily living or to die with dignity, and it consists of three stages which continually interact. Three types of nursing emerged inside this process of help. The relationships between (1) the nurse and different kinds of the art of nursing, (2) the nurse and various kinds of assumptions concerning the patient, and (3) the nurse and different kinds of co-operation with other health care personnel groups define the different types of process of help. The theory of nursing practice generated here is one that can be employed to test nurse orientation in many contexts. PMID- 1448023 TI - The role of the nurse teacher. AB - This paper reports on selected findings of a small exploratory study of the role of the nurse teacher. A questionnaire was circulated to teaching staff in one college of nursing. Quantitative data collected included a range of biographical detail, an outline of career patterns, professional qualifications and specific preparation undertaken for the teaching role. Qualitative data gathered in the study was transcribed and categorised into themes. The areas that are reported here include the identification of the factors that influenced decisions to work in nurse education, educator's views on preparation for the teaching role and areas of satisfaction and dissatisfaction in their work. Issues related to classroom teaching role, clinical teaching role, management and research are discussed. PMID- 1448024 TI - The perceptions of nurse teachers regarding the preparation for their role in Project 2000 programmes. AB - This paper discusses the findings related to the perceptions of nurse teachers regarding the preparation for their role in Project 2000 programmes. Data were collected by utilising three rounds of a Delphi survey with a panel of experts made up of Grade 2 nurse teachers. The panel of 201 respondents was obtained from 25 of the 28 colleges of nursing and midwifery that had implemented Project 2000 between September 1989 and April 1991. The profile of the respondents revealed that 68% work in general nurse courses, 18% in mental health, 8% in mental handicap and 6% in child care. Over half of the respondents hold a degree related to health care and over a quarter are studying for one. The findings suggest that the nurse teachers working in Project 2000 programmes consider their teacher preparation course an important means of preparation for the activities within their role. Degree and diploma courses are also considered important along with additional professional qualifying courses and subject related courses. What did not appear evident was any preparation for the many specific activities they carry out apart from teaching. Experience came out strongly as an important means of preparation for all the activities. Staff development programmes were said by 52% of respondents to be organised within their colleges and perceived by many as an important means of preparation. PMID- 1448025 TI - Planning, designing and developing an assessment tool for a 12-week accident emergency module as part of a pre-registration course: practical account. AB - The process of designing and developing an assessment tool for pre-registration students was governed by the need to assess students clinical competence during their 12-week exposure to the Accident and Emergency Department. It took the form of continuous assessment using a competency coding system ensuring criterion reference based assessment. PMID- 1448026 TI - An evaluation of a training course in the short-term management of violence. AB - Few comprehensive studies have been carried out regarding the nature and extent of violence towards staff in the caring professions. Scarcer still are studies which have thoroughly evaluated the impact of training in the management of violent and aggressive behaviour. Against this background, the following paper describes an evaluation of a 10-day in-service education course in the short-term management of violence. Set within an AB design, a combination of questionnaires and video rated role plays were used to investigate the impact of the training on the knowledge, effect and behaviour of course participants in two groups (N = 25). Results in most areas indicate that positive and significant changes have been brought about. Directions for future research in this area are identified and discussed. PMID- 1448027 TI - Devising a checklist to evaluate the non-verbal aspects of teaching skills and delivery. AB - This article proposes that teachers should constantly reflect upon and evaluate their performance if they are to improve teaching skills and delivery. Interaction Analysis and a true qualitative (anthropological) approach to evaluation are critically reviewed and are considered unsuitable for a teacher wanting to self-assess performances regularly. The use of a checklist in combination with video recording of the session to be evaluated is suggested as an alternative. An example of a checklist designed to focus on non verbal skills is given together with an overview of 'ideal' teacher behaviours. PMID- 1448028 TI - Hyaluronidase. PMID- 1448029 TI - Techniques for administration of i.v. medications/parenteral nutrition via central lines in the NICU: a pilot study. PMID- 1448030 TI - Incidence of patent ductus arteriosus with the use of surfactant. PMID- 1448031 TI - Congenital diaphragmatic hernia: pathophysiology and nursing care. PMID- 1448033 TI - It's common sense. PMID- 1448032 TI - Stressors reported by mothers of hospitalized premature infants. PMID- 1448034 TI - Support for the grieving family: a case study. PMID- 1448035 TI - Recommendation for practice, Part III. PMID- 1448036 TI - Neonatal radiology. Basic concepts and overview. PMID- 1448037 TI - Validity: controlling for variables in research studies involving high-risk neonates. PMID- 1448038 TI - Population-based mortality assessment--Baidoa and Afgoi, Somalia, 1992. AB - Since 1990, Somalia has been the site of an intense civil war that has disrupted health-care services and food delivery to a substantial part of the country. A regional drought, in combination with the ongoing civil disturbances, has further resulted in widespread famine. Multiple international government- and nongovernment-aid agencies are involved in the relief effort for Somalia. However, security problems in most areas of Somalia have prevented recent, systematic population-based assessments of the health and nutritional status of local Somali populations for use in directing relief efforts. To characterize the mortality of various Somali populations and to provide data on major population centers outside of the capital (Mogadishu), CDC, in collaboration with the United Nations Children's Fund (UNICEF) and the U.S. Agency for International Development, conducted a survey (1) of urban populations in a central region of Somalia (Figure 1). This report describes two pilot assessments performed during November 20-25 and December 5-6, 1992, in the towns of Baidoa and Afgoi. PMID- 1448039 TI - Update: poliomyelitis outbreak--Netherlands, 1992. PMID- 1448040 TI - Knowledge of the purpose of community water fluoridation--United States, 1990. AB - Expansion of water-fluoridation programs in the United States has been based on the clear documentation of the caries-preventive benefits of fluoride (1), as well as resources made available since the 1970s through the Fluoridation and Preventive Services Block grants administered by CDC. An estimated 135 million persons in the United States--approximately 61% of the population served by public water supplies--have access to drinking water with clinically important levels of fluoride (0.7 ppm or higher) for the prevention of dental caries (2). Efforts to expand the implementation of community water fluoridation require dissemination and understanding of information about health benefits and purported health risks. This report summarizes results from the 1990 National Health Interview Survey (NHIS) regarding public knowledge of the purpose and value of fluoridation of community drinking water.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448041 TI - Tuberculosis transmission in a state correctional institution--California, 1990 1991. AB - During September and October 1991, active tuberculosis (TB) was diagnosed in two inmates and one employee of a California state correctional institution (1991 average annual inmate population, 5421; employees, 1500). This report presents findings from an investigation by the California Department of Health Services (CDHS), the California Department of Corrections (CDOC), and CDC to determine whether ongoing transmission of Mycobacterium tuberculosis was occurring in the institution. PMID- 1448042 TI - [Protein turnover and amino acids metabolism in septic rats]. AB - This study was carried out to elucidate the protein and amino acids metabolism in septic rats, using constant infusion of 1-13C-leucine (4mg/hr), 5-13C-glutamine (2mg/hr), 1,2-13C-leucine (4mg/hr), or U-14C-leucine (2.0uCui/hr). Whole body protein kinetics showed that protein breakdown rate was increased in sepsis, but no change was found on protein synthesis rate (PSR). Intestinal mucosal fractional synthesis rate (FSR) was increased with sepsis. However, sepsis caused significant decrease of muscle FSR. Both leucine and glutamine oxidation rates were significantly increased in sepsis. Fraction of leucine degradation via glutamine was significantly increased in sepsis. We concluded that 1) both leucine and glutamine were utilized as important energy fuels in sepsis, 2) whole body PSR was influenced by the change of PSR in each organ, 3) the pathway from leucine to glutamine was significant in the degradation of leucine. PMID- 1448043 TI - [Induction of immunogenic variant of a murine fibrosarcoma]. AB - Immunogenic variant was induced from the methylcholanthrene induced fibrosarcoma (MCA-F) by in vitro treatment with the mutagen 1-methyl-3-nitro-1 nitrosoguanidine (MNNG). D-10 tumor cell which was cloned from MNNG treated MCA-F tumor cell was rejected by normal syngeneic C3H-HeJ mice but not by 650 rad irradiated immunosuppressed mice. Host which had rejected D-10 tumor growth, rejected parental MCA-F tumor cells. But active immunotherapy using D-10 tumor cell against MCA-F tumor cells. But active immunotherapy using D-10 tumor cell against MCA-F tumor bearing mice was not successful. Cytotoxic T cell (CTL) established from D-10 immunized spleen cells showed D-10 specific cytotoxic activity and not lysed parent MCA-F cells. CTL clone C-E-6 showed specific cytotoxic and proliferative activity against D-10 cell. In vivo tumor neutralizing assay also showed its specificity against D-10 tumor cell. Active immunotherapy and adoptive immunotherapy using immunogenic variant, D-10 was not successful. D-10 tumor cell possesses very strong neoantigen induced by MNNG treatment and parental MCA-F antigen. PMID- 1448044 TI - [Ultrasonographic finding of hemoperitoneum and indication for laparotomy in blunt abdominal trauma]. AB - The usefulness of the ultrasonography (US) for the indication for laparotomy was evaluated. I analyzed 200 blunt trauma patients who took US exams at my emergency center immediately after admission. Ninety-five percent of patients with hemodynamic instability, whose hemoperitoneum was revealed by US, underwent laparotomy. No negative laparotomy was performed in those patients. Only 5.4% of US hemoperitoneum-negative patients with stable hemodynamics required laparotomy because of peritoneal irritation or the evidence of traumatic diaphragmatic hernia. US hemoperitoneum-positive patients with stable hemodynamics were treated selectively, and 46% of such patients eventually underwent laparotomy, depending on findings of serial US, CT, DPL and Intravenous urogram. In two third of them laparotomy was indicated because of serial US showing the appearance or increase in hemoperitoneum. The maximum width of echo free space in Morison's pouch became more than 10 mm in the all exams when the laparotomy was indicated. I believe that US finding of hemoperitoneum should be an integral part of evaluating laparotomy indications in blunt abdominal trauma. PMID- 1448045 TI - [Study of postgastrectomy fatty liver]. AB - Fatty liver was often found concomitantly by the ultrasound during the follow up study of the gastric cancer operation. By ultrasound, development of postgastrectomy fatty liver was seen in 29 out of 176 patients (16.5%) with several gastrectomies. The number of the patients with postgastrectomy fatty liver was 12 out of 104 patients (11.5%) with distal partial gastrectomy with B-I reconstruction, while that was 17 of 72 patients (23.6%) with total gastrectomy with several reconstructions. The incidence of postoperative fatty liver change was significantly higher in the patients under 59 years old compared to the elders. Seventy-five g oral glucose test induced oxyhyperglycemia and hyperinsulinemia in patients with gastrectomy, especially with total gastrectomy. Integrated plasma insulin and triglyceride responses during first one hour in postgastrectomy patients were significantly higher than preoperative values. Moreover, plasma insulin and blood sugar in response to oral glucose test were significantly higher in patients with postgastrectomy fatty liver, compared to those in patients without fatty liver. These results suggested that the postgastrectomy fatty liver was resulted from the abnormality of the glucose metabolism. PMID- 1448046 TI - [Changes in hepatic volume following direct interrupting surgery for patients with esophageal varices]. AB - The aim of this study is to assess the long term changes in hepatic volume and liver function after direct interrupting surgery. Twenty-four patients with esophageal varices associated with idiopathic portal hypertension (IPH) or liver cirrhosis (LC) who received esophageal transection combined with splenectomy and paraesophago-cardial devascularization were studied, retrospectively. Volume of the liver was obtained by CT scan and was estimated before and after the operation. Plasma indocyanine green disappearance rate (KICG), body weight and liver function test were also evaluated at the same time. In patients with IPH, liver volume and KICG reduced significantly after direct interrupting surgery (liver volume: -21.3%, p < 0.01, KICG: -25.7%, p < 0.01). And in patients with LC, liver volume and KICG also significantly reduced after the surgery (liver volume: -9.6%, p < 0.05, KICG: -15.2%, p < 0.05). However, neither postoperative weight loss nor deterioration of hepatic function was observed. Decreasing rate of the liver volume showed a significant correlation to the spleen volume. These results suggest that interruption of the splenic blood flow by splenectomy leads to reduction of the effective hepatic blood flow and eventually to decrease in the liver volume. PMID- 1448047 TI - [An experimental study on mechanism of regurgitation of the intrabiliary endotoxin into the blood stream in obstructive jaundice]. AB - Using adult mongrel dogs with or without obstructive jaundice (OJ) the significance of the biliary pressure and the route of regurgitation were investigated by intrabiliary injection of endotoxin (ET) (10 micrograms/kg) or saline (control group) under various intrabiliary pressure levels (not carried, 25cmH2O, 35cmH2O). Some of dogs were cannulated into the thoracic duct for the purpose of drainage of the hepatic lymph. The dogs with OJ, of which the common biliary duct had been ligated and resected for two weeks, had ET shock under lower intrabiliary pressure level (25cmH2O) than the dogs without OJ. The drainage of the hepatic lymph could not attenuate ET shock. The ET volume per minute and the total ET volume extracted from the thoracic duct lymph was not increased in the dogs with OJ compared with the control group, while they were significantly increased in the dogs without OJ in proportion to the intrabiliary pressure level. These results suggest that in OJ, ET shock is easily caused by regurgitation of the intrabiliary ET into the blood stream under lower intrabiliary pressure level, and the intrabiliary ET is mainly regurgitated by cholangio-venous reflux, while the cholangio-lymphatic pathway does not function for the route of regurgitation. PMID- 1448048 TI - [Effectiveness of intraoperative cytological examination of peritoneal washings for patients with pancreatic cancer]. AB - To confirm the effectiveness of cytological examination of peritoneal washings for detecting invisible micro-peritoneal dissemination in patients with pancreatic cancer, results were analyzed with the survival and the background factors of the patients. Cytological examination of peritoneal washings or ascitic fluid at recto-vesical pouch or pouch of Douglas was performed in 37 patients with primary pancreatic cancer. Positive results for cancer cells were obtained in five of 9 patients (55.6%) who received cytological examination of ascitic fluid and in seven of 28 patients (25.0%) who received that of peritoneal washings. Four of 6 patients (66.7%) with visible peritoneal dissemination showed positive results. These 6 patients died of peritoneal dissemination with about 10 months. Eight of 31 patients (25.8%) without visible peritoneal dissemination showed positive results of the cytological examination. Two of the 8 patients received resection of the tumor. Other 6 patients without resection developed clinically evident peritoneal carcinomatosis. A high positive rate (66.7%) of cytological examination of the patients with visible peritoneal dissemination and a high incidence of appearance of peritoneal carcinomatosis in patients with positive cytological results but without visible peritoneal dissemination (75.0%; positive vs 26.1%; negative) indicate a high reliability of the cytological examination to detect invisible micro-peritoneal dissemination. PMID- 1448049 TI - [Prognostic factors of papillary carcinomas of the thyroid gland--retrospective multivariate analysis of 227 patients with median follow-up 130 months]. AB - I carried out the retrospective analysis of the prognostic factors of papillary carcinoma of the thyroid gland by using Cox's proportional hazard model using SAS program, and obtained the following conclusions. Two hundred and twenty seven patients who received surgical treatment under the diagnosis of carcinoma of the thyroid in the 1st Department Surgery of Yokohama City University during 24 years from 1964 to 1987 were subjected to this study. As prognostic factors, sex, age at the diagnosis, size of the tumor, presence of lymph node metastasis, number of the metastatic lymph nodes, presence of the local infiltration, presence of the distant metastasis and thyroidectomy were investigated. From these results, age at the diagnosis (chi 2 = 18.93, p < 0.0001, beta = 0.06, risk ratio = 0.203), presence of the local infiltration (chi 2 = 14.55, p < 0.0001, beta = 0.75, risk ratio = 0.175) and sex (chi 2 = 7.63, p < 0.01, beta = -0.91, risk ratio = 0.175) were considered statistically significant. Patients over 50 years of age at the diagnosis and presence of the local infiltration had high risk of death from papillary carcinoma of the thyroid gland. Particularly, age at the diagnosis was the most important prognostic factor. Therefore, it was considered that therapeutic approach taking age into consideration is important for the treatment of papillary carcinoma of the thyroid. PMID- 1448050 TI - [A role of interpectoral (Rotter's) lymph node dissection in modified radical mastectomy for breast cancer]. AB - To study the influence of interpectoral lymph node (IPN) dissection on the prognosis of patients who underwent modified radical mastectomy, IPN was carefully dissected and studied pathologically on 168 cases of our breast cancer patients operated with modified radical mastectomy. There were 1.2 lymph nodes on an average in the interpectoral region, and they were almost 1-2mm in diameter. IPN metastases were found in 10 cases. (Tis: 0%, Stage I: 4.9%, Stage II: 5.7%, Stage III: 13%). Tumors located in outer quadrant in almost all these cases. Positive IPN were found in 6 (16%) of n1 alpha group, 1 (10%) of n1 beta group, and in 3 (50%) of n2 group. All these 3 cases of n2 died of distant metastasis and local recurrence. Two (1.7%) of axillary node (1a, 1b) negative patients had microinvolvement of cancer only in IPN, and are currently disease-free. These data suggest that IPN metastasis may occur even in the early breast cancer patients, and that may be controllable by lymph node excision. Therefore, routine and careful dissection of IPN through wide opening of sulcus interpectoralis is necessary for modified radical mastectomy and even for breast preserving operation. PMID- 1448051 TI - [Operative strategy for thoracoabdominal aortic aneurysm with concomitant reconstruction of four main abdominal branches]. AB - A thoracoabdominal aortic aneurysm (TAAA) involving major abdominal branches remains still difficult to be managed. From 1983 to 1990, we successfully operated five such cases. Our operative strategy for TAAA which necessitates concomitant reconstruction of four major abdominal branches is i) to utilize temporary bypass to maintain distal perfusion during aortic cross-clamping, ii) to reconstruct bilateral renal arteries prior to aortic clamping in order to shorten renal ischemic time as much as possible, iii) to reconstruct celiac and superior mesenteric arteries by Crawford's method, iv) to reconstruct two pairs of intercostal arteries by using diagonal anastomosis in the proximal site, and v) to divide the left renal vein temporarily for easy manipulation of renal arteries. All five cases were recovered uneventfully. This procedure, in which the renal ischemic time is saved as short as possible, is considered a safe and reasonable one for thoracoabdominal aortic aneurysms. PMID- 1448052 TI - [Serum and tissue lysosomal enzymes and liver dysfunction after an experimental acute lower limbs ischemia in the rats]. AB - Adult male Wistar rats were divided in 3 groups. In the first group, infrarenal abdominal aorta was occluded for 6 hours and reperfused thereafter. In the second group, the reperfusion was not made, and the third group underwent a sham operation. Lysosomal enzymatic activities were assessed in serum tissues. Lysosomal membrane fragilities were estimated also in these tissues. Finally, 14C aminopyrine breath test (ABT) was studied to define the possible liver dysfunction caused by limb ischemia. As a result, release of lysosomal enzymes from ischemic muscle was confirmed in vitro experiments, and the increase in the serum was statistically significant in the first and second groups as compared to the third group. Particularly prominent was a marked elevation of cathepsin-D in the first group which was observed immediately after the release of occlusion. Results of liver lysosomal enzymes and ABT revealed significant cellular damages and depression of microsomal function of the liver both in the first and second groups. These studies suggest that lysosomal enzymes derived from ischemic muscle exert a possible toxicity on the liver, and liver damage thus resulted may play a roll on the pathogenesis of whole body injury associated with acute and critical lower limb ischemia. PMID- 1448053 TI - [Cytotoxic effect of CPT-11 against human recurrent carcinoma cells primarily cultured on contact-sensitive plates: preliminary report]. PMID- 1448054 TI - [The small caliber prosthesis provided healing characteristics by plasmin-treated fibrin: preliminary report]. PMID- 1448055 TI - [The fundamental study of the water jet angioplasty: preliminary report]. PMID- 1448056 TI - Dietary level of protein regulates glyceraldehyde-3-phosphate dehydrogenase content and synthesis rate in mouse liver cytosol. AB - The content of liver cytosolic proteins was studied in mice subjected to protein depletion followed by refeeding with a normal diet. Depletion elicited either the accumulation or the decrease of several polypeptides, being the early increase of a M(r) 36,000 polypeptide the most pronounced change observed. The refeeding with a normal diet for 2 days caused a return of the cytosol protein composition to that of normally fed animals. The M(r) 36,000 polypeptide was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Its molecular weight, the sequence of its first twenty amino acid residues, its amino acid composition and its antigenic properties were found to be similar with those of GAPDH from different mammalian cells. During the first 2 days of protein depletion, both the GAPDH polypeptide content and activity increased. Thereafter, the enzymatic activity of GAPDH decreased, whereas GAPDH protein mass decreased in a lesser extent. The accumulation of GAPDH and other particular polypeptides in the cytosols of protein depleted mice was associated with an increased synthesis. The refeeding with a normal diet caused an immediate return to the synthesis pattern of normal livers. PMID- 1448058 TI - Dual anomeric specificity of phosphomannoisomerase assessed by 2D phase sensitive 13C EXSY NMR. AB - The reversible conversion between D-mannose 6-phosphate and D-fructose 6 phosphate catalyzed by yeast phosphomannoisomerase was studied by phase sensitive 2D 13C-(1H) EXSY NMR spectroscopy at 100.623 MHz, using 13C enriched substrates in the C2 position of the D-hexose 6-phosphates. The unique pair of isomerization cross-peaks observed in the 2D EXSY map correlates the 13C2 resonances of the beta-anomers of both D-[2-13C]-mannose 6-phosphate and D-[213C]-fructose 6 phosphate. This indicates that phosphomannoisomerase specifically catalyzes the reversible conversion between beta-D-mannose 6-phosphate and beta-D-fructose 6 phosphate. Since phosphoglucoisomerase was recently found to catalyze specifically the interconversion of alpha-D-glucose 6-phosphate and beta-D fructose 6-phosphate, the beta-anomer of the ketohexose ester could be directly channeled in a multi-enzyme system involving phosphoglucoisomerase, phosphomannoisomerase and phosphofructokinase. PMID- 1448057 TI - Evidence for a lack of functional receptors for nerve growth factor (NGF) in chick bone cells in vitro. AB - Nerve growth factor (NGF) is essential for the development and differentiation of sympathetic and sensory neurons. Recently, NGF receptors were demonstrated in non neural cells, and several mesenchymal cell types including lymphocytes and skeletal myotubes were shown to be stimulated to proliferate by NGF. Our purpose was to examine for the presence of functional NGF receptors in osteoblasts. Bone cells from chick calvaria were used as a model; PC-12 cells derived from rat adrenal pheochromocytoma were used as positive controls. NGF was examined for functions in chick bone cells by studying effects on (1) [3H]-thymidine incorporation; (2) alkaline phosphatase (ALP) activity; and (3) protein tyrosine phosphorylation. Effects of NGF on thymidine incorporation and protein tyrosine phosphorylation by PC-12 cells were also measured. A radioreceptor assay was used to test for the presence of receptors. In chick calvarial cells, NGF had no effect on thymidine incorporation, ALP activity or protein tyrosine phosphorylation. Radioreceptor assay with bone cells showed no evidence of NGF receptors. In contrast, in PC-12 cells, NGF (1) decreased thymidine incorporation; (2) increased protein tyrosine phosphorylation; and (3) showed receptor activity by radioreceptor assay. In conclusion, unlike several other mesenchymal cell types, chick bone cells show no evidence of NGF receptors or functional responses to NGF in vitro. PMID- 1448059 TI - Effect of ethanol on hepatic ribosomal proteins and mRNA. AB - Levels of RNA, mRNA and separation of ribosomal proteins from control and ethanol treated rat liver, showed no change in total RNA content, but poly(A+)mRNA was reduced significantly in ethanolic rats. Ribosomal proteins S2, S3a, S3b, S4, L3, L4, L4a, L10a and L15 were found substantially reduced in experimental rat livers. This study suggests decrease in poly(A+) mRNA coupled with loss of ribosomal proteins must be responsible for decreased protein synthesis in chronic alcoholism. PMID- 1448060 TI - Alterations in human gingival glycosaminoglycan pattern in inflammation and in phenytoin induced overgrowth. AB - Glycosaminoglycans were extracted from normal, inflamed and phenytoin induced overgrowth of human gingival tissue by proteolysis and alcohol precipitation. Extracts were run in a Dowex-1 column and the fractions were treated with mucopolysaccharidases. Cellulose acetate electrophoresis was carried out with or without enzyme digestion for identification of individual glycosaminoglycans. Glycosaminoglycans were found to be decreased in inflammation but were observed to increase in the overgrowth. Hyaluronic acid was found to be increased in both the pathological conditions. Dermatan sulphate, chondroitin sulphate and heparan sulphate were observed to be decreased in inflammation. In overgrowth, dermatan sulphate and chondroitin sulphate were found to increase while the presence of heparan sulphate was not significant. The changes in the pattern of individual glycosaminoglycan in the two varied conditions are discussed. PMID- 1448061 TI - Presence of a highly specific histone H1-like protein in the chromatin of the sperm of the bivalve mollusks. AB - Chromatin organization in the sperm of the bivalve mollusks results from the interaction between a discrete number of protamine-like proteins (PL) and DNA. A small variable amount of histones is also present. An extensive study carried out on a relatively large number of species, within the class Bivalvia, has shown that it is possible to arrange these mollusks into five major categories on the basis of their PL composition (Ausio, J. Comp. Biochem. Physiol. 85, 439-449, (1986) [1]). In the present work, we have extended this analysis to a larger number of species and found that in spite of the inter- and intra-specific similarity of all PL proteins in their chemical composition, they exhibit different degrees of structural variability. Moreover one of these PL proteins is present in all the species analyzed, and bears an enormous resemblance to histones of the H1 family. The evolutionary significance of this finding is discussed. PMID- 1448062 TI - Homeostatic restoration of microsomal lipids and enzyme changes in HMG-CoA reductase and acyl-CoA: cholesterol acyltransferase in chick liver. AB - We have studied the correlation between changes in the lipid composition in chick liver microsomes and the activities of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and acyl-CoA: cholesterol acyltransferase (ACAT) by in vivo and in vitro experiments with 21-day-old chicks. A 5% cholesterol diet for 3 hr produced an increase in the microsomal and plasmatic cholesterol content, a decrease in HMG-CoA reductase activity and a concomitant increase in ACAT activity. The effect produced by the short-term treatment virtually disappeared 27 hr after ending the cholesterol diet. In vitro experiments were carried out by using vesicles constituted by phosphatidylcholine/cholesterol and phosphatidylcholine. PMID- 1448063 TI - The effects of insulin, cycloheximide and phalloidin on the content of actin and p35 in extracts prepared from the nuclear fraction of Krebs II ascites cells. AB - The nuclear fraction isolated from Krebs II ascites cells following cell disruption by nitrogen cavitation was separated into four fractions by salt/detergent extraction: NP-40 soluble fraction, 130 mM KCl extract, DOC/Triton x 100 soluble fraction and salt/detergent treated nuclei. The protein composition of the individual fractions was studied by SDS-PAGE and the relative amounts of actin and a 35 kDa protein (p35) were measured from gel scans. There was a time dependent shift of actin from the 130 mM KCl extract to the NP-40 soluble fraction upon storage of the nuclear fraction on ice, indicating a progressive depolymerization of microfilaments. Compared with actin there was a slower release of p35 into the NP-40 soluble fraction. The results suggest that p35 is not integrated in the microfilament network. Phalloidin, which stabilizes the microfilaments, enriched the amount of both proteins in the 130 mM KCl extracts, together with a series of other proteins in the range 50-205 kDa. The presence of phalloidin also resulted in a large increase in the actin content in both the DOC/Triton x 100 extract and the fraction containing salt/detergent treated nuclei. Incubation of cells with insulin and/or cycloheximide enriched the amount of actin in the 130 mM KCl fraction. The results show that short term incubation of cells with phalloidin, insulin or cycloheximide increases the actin content of the nuclear fraction and also affects the presence of several other proteins. PMID- 1448064 TI - The effect of ischaemia-reperfusion on [3H]inositol phosphates and ins(1,4,5)P3 levels in cardiac atria and ventricles--a comparative study. AB - In this study incorporation of [3H]inositol into inositol phosphates and phosphoinositides as well as tissue Ins(1,4,5)P3 levels of the atria and ventricles of isolated, perfused rat hearts were compared. Although the incorporation of [3H]inositol into the phosphoinositides of atria and ventricles was similar, significantly higher (2-3 fold) incorporation rates into inositol phosphates were observed in atrial tissue. Using a D-myo-[3H]Ins(1,4,5)P3 assay system, the Ins(1,4,5)P3 levels observed in atria from perfused rat hearts were also significantly higher than those obtained under the same experimental circumstances in the ventricles. Since previous studies on whole hearts showed inhibition of the phosphatidylinositol (PI) pathway during ischaemia with an immediate significant stimulation upon reperfusion [12, 20], the effects of ischaemia and 1 min postischaemic reperfusion were also examined separately in atria and ventricles. The results showed that 20 min of global ischaemia significantly depressed Ins(1,4,5)P3 levels as well as incorporation of [3H]inositol into ventricular InsP2 and InsP3. Reperfusion caused an immediate (within 1 min) increase in Ins(1,4,5)P3 levels and also [3H]inositol incorporation into all three cytosolic inositol phosphates in the ventricles. However, the effect of ischaemia and reperfusion on Ins(1,4,5)P3 levels as well as the incorporation of [3H]inositol into the inositol phosphates were less prominent in the atria. It therefore appears that the differential responses of the atria and the ventricles to an oxygen deficiency [41] are also reflected in the differences in PI metabolism during ischaemia-reperfusion. PMID- 1448065 TI - A novel 7-nucleotide motif located in 3' untranslated sequences of the immediate early gene set mediates platelet-derived growth factor induction of the JE gene. AB - A cohort of the serum and growth factor regulated immediate-early gene set is induced with slower kinetics than c-fos. Two of the first immediate-early genes characterized as such, c-myc and JE, are contained within this subset. cis-acting genomic elements mediating induction of the slower responding subset of immediate early genes have never been characterized. Herein we characterize two widely separated genomic elements which are together essential for induction of the murine JE gene by platelet-derived growth factor, serum, interleukin-1, and double-stranded RNA. One of these elements is novel in several regards. It is a 7 mer, TTTTGTA, found in the proximal 3' sequences downstream of the JE stop codon. The 3' element is position dependent and orientation independent. It does not function in polyadenylation, splicing, or destabilization of the JE transcript. Copies of the 7-mer or its inverse are found at comparable 3' sites in 25 immediate-early genes that encode transcription factors or cytokines. Given its general occurrence, the 7-mer may be a required cis-acting control element mediating induction of the immediate-early gene set. PMID- 1448066 TI - Purine biosynthetic genes are required for cadmium tolerance in Schizosaccharomyces pombe. AB - Phytochelatins (PCs) are metal-chelating peptides produced in plants and some fungi in response to heavy metal exposure. A Cd-sensitive mutant of the fission yeast Schizosaccharomyces pombe, defective in production of a PC-Cd-sulfide complex essential for metal tolerance, was found to harbor mutations in specific genes of the purine biosynthetic pathway. Genetic analysis of the link between metal complex accumulation and purine biosynthesis enzymes revealed that genetic lesions blocking two segments of the pathway, before and after the IMP branchpoint, are required to produce the Cd-sensitive phenotype. The biochemical functions of these two segments of the pathway are similar, and a model based on the alternate use of a sulfur analog substrate is presented. The novel participation of purine biosynthesis enzymes in the conversion of the PC-Cd complex to the PC-Cd-sulfide complex in the fission yeast raises an intriguing possibility that these same enzymes might have a role in sulfur metabolism in the fission yeast S. pombe, and perhaps in other biological systems. PMID- 1448068 TI - Hydrolysis of phosphatidylcholine is stimulated by Ras proteins during mitogenic signal transduction. AB - We have used a dominant inhibitory ras mutant (Ha-ras Asn-17) to investigate the relationship of Ras proteins to hydrolysis of phosphatidylcholine (PC) in the transduction of mitogenic signals. Expression of Ha-Ras Asn-17 inhibited NIH 3T3 cell proliferation induced by polypeptide growth factors or phorbol esters. In contrast, the mitogenic activity of PC-specific phospholipase C (PC-PLC) was not inhibited by Ha-Ras Asn-17 expression. Similarly, cotransfection with a cloned PC PLC gene bypassed the block to NIH 3T3 cell proliferation resulting from expression of the inhibitory ras mutant. Hydrolysis of PC can therefore induce cell proliferation in the absence of normal Ras activity, suggesting that PC derived second messengers may act downstream of Ras in mitogenic signal transduction. This was substantiated by the finding that Ha-Ras Asn-17 expression inhibited growth factor-stimulated hydrolysis of PC. Taken together, these results indicate that PC hydrolysis is a target of Ras during the transduction of growth factor-initiated mitogenic signals. PMID- 1448067 TI - Specific changes of Ras GTPase-activating protein (GAP) and a GAP-associated p62 protein during calcium-induced keratinocyte differentiation. AB - Induction of tyrosine phosphorylation occurs as an early and specific event in keratinocyte differentiation. A set of tyrosine-phosphorylated substrates which transduce mitogenic signals by tyrosine kinases has previously been identified. We show here that of these substrates, the Ras GTPase-activating protein, GAP, is specifically affected during calcium-induced keratinocyte differentiation. As early as 10 min after calcium addition to cultured primary mouse keratinocytes, GAP associates with tyrosine-phosphorylated proteins and translocates to the membrane. In addition, a GAP-associated protein of approximately 62 kDa (p62) becomes rapidly and heavily tyrosine phosphorylated in both membrane and cytosolic fractions. This protein corresponds to the major tyrosine phosphorylated protein that is induced in differentiating keratinocytes as early as 5 min after calcium addition. p62 phosphorylation was not observed after exposure of these cells to epidermal growth factor, phorbol ester, or transforming growth factor beta. In contrast, PLC gamma and P13K were tyrosine phosphorylated after epidermal growth factor, but not calcium, stimulation. Thus, changes of Ras GAP and an associated p62 protein occur as early and specific events in keratinocyte differentiation and appear to involve a calcium-induced tyrosine kinase. PMID- 1448069 TI - Multiple in vivo footprints are specific to the active allele of the X-linked human hypoxanthine phosphoribosyltransferase gene 5' region: implications for X chromosome inactivation. AB - Dosage compensation of X-linked genes in male and female mammals is accomplished by random inactivation of one X chromosome in each female somatic cell. As a result, a transcriptionally active allele and a transcriptionally inactive allele of most X-linked genes reside within each female nucleus. To examine the mechanism responsible for maintaining this unique system of differential gene expression, we have analyzed the differential binding of regulatory proteins to the 5' region of the human hypoxanthine phosphoribosyltransferase (HPRT) gene on the active and inactive X chromosomes. Studies of DNA-protein interactions associated with the transcriptionally active and inactive HPRT alleles were carried out in intact cultured cells by in vivo footprinting by using ligation mediated polymerase chain reaction and dimethyl sulfate. Analysis of the active allele demonstrates at least six footprinted regions, whereas no footprints were detected on the inactive allele. Of the footprints on the active allele, at least four occur over canonical GC boxes or Sp1 consensus binding sites, one is associated with a potential AP-2 binding site, and another is associated with a DNA sequence not previously reported to interact with a sequence-specific DNA binding factor. While no footprints were observed for the HPRT gene on the inactive X chromosome, reactivation of the inactive allele with 5-azacytidine treatment restored the in vivo footprint pattern found on the active allele. Results of these experiments, in conjunction with recent studies on the X-linked human PGK-1 gene, bear implications for models of X chromosome inactivation. PMID- 1448070 TI - Mitogenic signaling by colony-stimulating factor 1 and ras is suppressed by the ets-2 DNA-binding domain and restored by myc overexpression. AB - The activity of p21ras is required for the proliferative response to colony stimulating factor 1 (CSF-1), and signals transduced by both the CSF-1 receptor (CSF-1R) and p21ras stimulate transcription from promoter elements containing overlapping binding sites for Fos/Jun- and Ets-related proteins. A sequence encoding the DNA-binding domain and nuclear localization signal of human c-ets-2, which lacked portions of the c-ets-2 gene product necessary for trans activation, was fused to the bacterial lacZ gene and expressed from an actin promoter in NIH 3T3 cells expressing either the v-ras oncogene or human CSF-1R. Nuclear expression of the Ets-LacZ protein, confirmed by histochemical staining of beta galactosidase, inhibited the activity of ras-responsive enhancer elements and suppressed morphologic transformation by v-ras as well as CSF-1R-dependent colony formation in semisolid medium. When CSF-1R-bearing cells expressing the Ets-LacZ protein were stimulated by CSF-1, induction of c-ets-2, c-jun, and c-fos ensued, but the c-myc response was impaired. Enforced expression of the c-myc gene overrode the suppressive effect of ets-lacZ and restored the ability of these cells to form colonies in response to CSF-1. NIH 3T3 cells engineered to express a CSF-1R (Phe-809) mutant similarly cannot form CSF-1-dependent colonies in semisolid medium and exhibit an impaired c-myc response, but expression of an exogenous myc gene resensitizes these cells to CSF-1 [M. F. Roussel, J. L. Cleveland, S. A. Shurtleff, and C. J. Sherr, Nature (London) 353:361-363, 1991]. The ability of these cells to respond to CSF-1 was also rescued by enforced expression of an endogenous c-ets-2 gene. The ets family of transcription factors therefore plays a central role in integrating both CSF-1R and ras-induced mitogenic signals and in modulating the myc response to CSF-1 stimulation. PMID- 1448071 TI - Biological function of the retinoblastoma protein requires distinct domains for hyperphosphorylation and transcription factor binding. AB - Despite the importance of the retinoblastoma susceptibility gene to tumor growth control, the structural features of its encoded protein (pRb) and their relationship to protein function have not been well explored. We constructed a panel of deletion mutants of pRb expression vectors and used a biological assay for pRb that measures growth inhibition and morphologic changes in pRb transfected Saos-2 cells to correlate structural alterations of the pRb coding region with function. We tested the deleted proteins for the ability to bind to viral oncoprotein E1A and to the transcription factor E2F. We also measured the ability of the mutant proteins to become hyperphosphorylated in vivo and to be recognized as substrates in vitro by a cell cycle-regulatory kinase associated with cyclin A. We identified two regions of pRb that are required for E2F binding and for hyperphosphorylation. E1A binding domains partially overlap but are distinct from both of these other two regions. Biological function of pRb is dependent on retention of the integrity of both of these biochemically defined domains. These data support the model that pRb is a transducer of afferent signals (via the kinase that phosphorylates it) and efferent signals (through transcription factor binding), using distinct structural elements. Preservation of both of these features is essential for the ability of pRb to induce growth inhibition and morphologic changes upon reintroduction into transfected cells. PMID- 1448072 TI - Hypoxic induction of the human erythropoietin gene: cooperation between the promoter and enhancer, each of which contains steroid receptor response elements. AB - Transcription of the human erythropoietin (Epo) gene is stimulated by exposure to hypoxia and/or cobalt in whole animals and in Hep3B cells. We have systematically investigated the promoter and 3' enhancer elements necessary for this induction by transient transfection of Hep3B cells. We define a promoter region of 53 bp and an enhancer region of 43 bp that confer hypoxia and cobalt inducibility. Each element gives rise to a 6- to 10-fold induction alone. In combination they produce a 50-fold induction after stimulation, similar to the 50- to 100-fold induction of the endogenous Epo gene. Two areas of DNA sequence homology are present in these regions. We demonstrate specific DNA-protein interactions in the enhancer and the ability of the promoter element to compete with these interactions in electrophoretic mobility shift assays. DNase I footprinting and methylation interference data further refine the cis-acting element in the 43-bp enhancer to a short region containing a direct repeat of a steroid/thyroid hormone receptor response element half-site separated by a 2-bp gap. Two half site consensus sequences are also present in the 53-bp promoter. Site-specific mutation of the half-site sequences in the enhancer destroys the functional activity of the enhancer. PMID- 1448074 TI - Several distinct types of sequence elements are required for efficient mRNA 3' end formation in a pea rbcS gene. AB - We have conducted an extensive linker substitution analysis of the polyadenylation signal from a pea rbcS gene. From these studies, we can identify at least two, and perhaps three, distinct classes of cis element involved in mRNA 3' end formation in this gene. One of these, termed the far-upstream element, is located between 60 and 120 nt upstream from its associated polyadenylation sites and appears to be largely composed of a series of UG motifs. A second, termed the near-upstream element, is more proximate to poly(A) sites and may be functionally analogous to the mammalian polyadenylation signal AAUAAA, even though the actual sequences involved may not be AAUAAA. The third possible class is the putative cleavage and polyadenylation site itself. We find that the rbcS-E9 far-upstream element can replace the analogous element in another plant polyadenylation signal, that from cauliflower mosaic virus, and that one near-upstream element can function with either of two poly(A) sites. Thus, these different cis elements are largely interchangeable. Our studies indicate that a cellular plant gene possesses upstream elements distinct from AAUAAA that are involved in mRNA 3' end formation and that plant genes probably have modular, multicomponent polyadenylation signals. PMID- 1448073 TI - ACR1, a yeast ATF/CREB repressor. AB - Members of the mammalian ATF/CREB family of transcription factors, which are associated with regulation by cyclic AMP and viral oncogenes, bind common DNA sequences (consensus TGACGTCA) via a bZIP domain. In the yeast Saccharomyces cerevisiae, ATF/CREB-like sequences confer either repression or activation of transcription, depending on the promoter context. By isolating mutations that alleviate the repression mediated by ATF/CREB sites, we define a new yeast gene, ACR1, which encodes an ATF/CREB transcriptional repressor. ACR1 contains a bZIP domain that is necessary for homodimer formation and specific DNA binding to an ATF/CREB site. Within the bZIP domain, ACR1 most strongly resembles the mammalian cyclic AMP-responsive transcriptional regulators CREB and CREM; it is less similar to GCN4 and YAP1, two previously described yeast bZIP transcriptional activators that recognize the related AP-1 sequence (consensus TGACTCA). Interestingly, deletion of the ACR1 gene causes increased transcription through ATF/CREB sites that does not depend on GCN4 or YAP1. Moreover, extracts from acr1 deletion strains contain one or more ATF/CREB-like DNA-binding activities. These genetic and biochemical observations suggest that S. cerevisiae contains a family of ATF/CREB proteins that function as transcriptional repressors or activators. PMID- 1448075 TI - Effect of terminal nonhomologies on homologous recombination in Xenopus laevis oocytes. AB - Homologous recombination of linear DNA molecules in Xenopus laevis oocytes is very efficient. The predictions of molecular models for this recombination process were tested with substrates with terminal nonhomologies (nonhomologous sequences). It was found that nonhomologies on one or both ends of an otherwise efficient substrate substantially reduced the yield of recombination products. In the case of a single nonhomology, inhibition was observed for all lengths of nonhomology, from 60 to 1,690 bp, being most dramatic for the longer blocks. Examination of time courses of recombination showed that the blocks were largely kinetic; that is, substrates with short nonhomologies eventually yielded substantial levels of completed products. Intermediates that accumulated after the injection of end-blocked substrates were characterized by two-dimensional gel electrophoresis and hybridization with strand-specific oligonucleotide probes. These blocked intermediates were shown to have base-paired junctions, but resolution was prevented by the failure to remove the 3'-ending strand of the original nonhomology. Continuing exonuclease action created a single-strand gap adjacent to the position of the persistent nonhomology. In contrast, the strand that included the unblocked side of the junction could be sealed. These results are consistent with a nonconservative, resection-annealing mechanism of homologous recombination in the oocytes and suggest the absence of any activity that can efficiently remove 3' tails. PMID- 1448076 TI - p59fyn tyrosine kinase associates with multiple T-cell receptor subunits through its unique amino-terminal domain. AB - Several lines of evidence link the protein tyrosine kinase p59fyn to the T-cell receptor. The molecular basis of this interaction has not been established. Here we show that the tyrosine kinase p59fyn can associate with chimeric proteins that contain the cytoplasmic domains of CD3 epsilon, gamma, zeta (zeta), and eta. Mutational analysis of the zeta cytoplasmic domain demonstrated that the membrane proximal 41 residues of zeta are sufficient for p59fyn binding and that at least two p59fyn binding domains are present. The association of p59fyn with the zeta chain was specific, as two closely related Src family protein tyrosine kinases, p60src and p56lck, did not associate with a chimeric protein that contained the cytoplasmic domain of zeta. Mutational analysis of p59fyn revealed that a 10 amino-acid sequence in the unique amino-terminal domain of p59fyn was responsible for the association with zeta. These findings support evidence that p59fyn is functionally and structurally linked to the T-cell receptor. More importantly, these studies support a critical role for the unique amino-terminal domains of Src family kinases in the coupling of tyrosine kinases to the signalling pathways of cell surface receptors. PMID- 1448077 TI - A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. AB - We have identified a 50-nucleotide enhancer from the human erythropoietin gene 3' flanking sequence which can mediate a sevenfold transcriptional induction in response to hypoxia when cloned 3' to a simian virus 40 promoter-chloramphenicol acetyltransferase reporter gene and transiently expressed in Hep3B cells. Nucleotides (nt) 1 to 33 of this sequence mediate sevenfold induction of reporter gene expression when present in two tandem copies compared with threefold induction when present in a single copy, suggesting that nt 34 to 50 bind a factor which amplifies the induction signal. DNase I footprinting demonstrated binding of a constitutive nuclear factor to nt 26 to 48. Mutagenesis studies revealed that nt 4 to 12 and 19 to 23 are essential for induction, as substitutions at either site eliminated hypoxia-induced expression. Electrophoretic mobility shift assays identified a nuclear factor which bound to a probe spanning nt 1 to 18 but not to a probe containing a mutation which eliminated enhancer function. Factor binding was induced by hypoxia, and its induction was sensitive to cycloheximide treatment. We have thus defined a functionally tripartite, 50-nt hypoxia-inducible enhancer which binds several nuclear factors, one of which is induced by hypoxia via de novo protein synthesis. PMID- 1448078 TI - Histone H3 transcription in Saccharomyces cerevisiae is controlled by multiple cell cycle activation sites and a constitutive negative regulatory element. AB - The promoters of the Saccharomyces cerevisiae histone H3 and H4 genes were examined for cis-acting DNA sequence elements regulating transcription and cell division cycle control. Deletion and linker disruption mutations identified two classes of regulatory elements: multiple cell cycle activation (CCA) sites and a negative regulatory site (NRS). Duplicate 19-bp CCA sites are present in both the copy I and copy II histone H3-H4 promoters arranged as inverted repeats separated by 45 and 68 bp. The CCA sites are both necessary and sufficient to activate transcription under cell division cycle control. A single CCA site provides cell cycle control but is a weak transcriptional activator, while an inverted repeat comprising two CCA sites provides both strong transcriptional activation and cell division cycle control. The NRS was identified in the copy I histone H3-H4 promoter. Deletion or disruption of the NRS increased the level of the histone H3 promoter activity but did not alter the cell division cycle periodicity of transcription. When the CCA sites were deleted from the histone promoter, the NRS element was unable to confer cell division cycle control on the remaining basal level of transcription. When the NRS element was inserted into the promoter of a foreign reporter gene, transcription was constitutively repressed and did not acquire cell cycle regulation. PMID- 1448079 TI - Multiple functional domains of human U2 small nuclear RNA: strengthening conserved stem I can block splicing. AB - We showed previously that a branch site mutation in simian virus 40 early pre mRNA that prevented small t antigen mRNA splicing could be efficiently suppressed by a compensatory mutation in a coexpressed U2 small nuclear (sn) RNA gene. We have now generated second-site mutations in this suppressor gene to investigate regions of U2 RNA required for function. A number of mutations in a putative stem at the 5' end of the molecule inhibited splicing, indicating that bases in this region are important for activity. However, several lines of evidence suggested that formation of the entire stem is not essential for splicing. Indeed, mutations that strengthen the stem actually inhibited splicing, and evidence that this prevents a required base-pairing interaction with U6 snRNA is presented. These results suggest that the relative stabilities of competing intra- and intermolecular base-pairing interactions play an important role in the splicing reaction. Mutations in a conserved single-stranded region immediately 3' to the branch site recognition sequence all inhibited splicing, indicating that this region is required for U2 function, although its exact role remains unknown. Finally, two mutations in the loop of stem IV at the 3' end of the molecule, which destroy the binding site of U2 sn ribonucleoprotein B", prevented small t splicing; this finding contrasts with previous studies which utilized different assay systems. Analysis of the accumulation and subcellular localization of all of the mutant RNAs showed that they were similar to those of the parental suppressor U2 RNA, indicating that the effects observed indeed reflect defects in splicing. PMID- 1448080 TI - Fission yeast pap1-dependent transcription is negatively regulated by an essential nuclear protein, crm1. AB - The fission yeast pap1+ gene encodes an AP-1-like transcription factor that contains a leucine zipper motif. We identified a target gene of pap1, the p25 gene. The 5' upstream region of the p25 gene contains an AP-1 site, and by DNase I footprint analysis, we showed that the pap1 protein binds to the AP-1 site as well as to a 14-bp palindrome sequence. p25 is overproduced when the pap1+ gene is overexpressed, whereas p25 is not produced at all in the pap1 deletion mutant. p25 was previously found to be overproduced in strains carrying cold-sensitive crm1 mutations whose gene product is essential for viability and is thought to play an important role in maintenance of a proper chromosomal architecture. Deletion and site-directed mutagenesis of sequences upstream of the p25 gene demonstrated that the AP-1 site as well as the palindrome sequence are crucial for transcriptional activation either by pap1 overproduction or by the cold sensitive crm1 mutation; pap1+ is apparently negatively regulated by crm1+. Moreover, we found that cold-sensitive crm1 mutations are suppressed by the deletion of pap1+, further indicating a close relationship between crm1+ and pap1+. The crm1 protein is highly conserved; the budding yeast homolog, CRM1, which complements the fission yeast cold-sensitive crm1 mutation, was isolated and found to also be essential for viability. These results suggest the functional importance of chromosome structure on the regulation of gene expression through the pap1 transcription factor. PMID- 1448081 TI - Unstable amplification of two extrachromosomal elements in alpha difluoromethylornithine-resistant Leishmania donovani. AB - We describe the first example of unstable gene amplification consisting of linear extrachromosomal DNAs in drug-resistant eukaryotic cells. alpha Difluoromethylornithine (DFMO)-resistant Leishmania donovani with an amplified ornithine decarboxylase (ODC) gene copy number contained two new extrachromosomal DNAs, both present in 10 to 20 copies. One of these was a 140-kb linear DNA (ODC140-L) on which all of the amplified copies of the odc gene were located. The second was a 70-kb circular DNA (ODC70-C) containing an inverted repeat but lacking the odc gene. Both ODC140-L and ODC70-C were derived from a preexisting wild-type chromosome, probably by a conservative amplification mechanism. Both elements were unstable in the absence of DFMO, and their disappearance coincided with a decrease in ODC activity and an increase in DFMO growth sensitivity. These results suggest the possibility that ODC70-C may play a role in DFMO resistance. These data expand the diversity of known amplification mechanisms in eukaryotes to include the simultaneous unstable amplification of both linear and circular DNAs. Further characterization of these molecules will provide insights into the molecular mechanisms underlying gene amplification, including the ability of linear amplified DNAs to acquire telomeres and the determinants of chromosomal stability. PMID- 1448082 TI - A common intermediary factor (p52/54) recognizing "acidic blob"-type domains is required for transcriptional activation by the Jun proteins. AB - The ability of the c-Jun protein, the main component of the transcription factor AP1, to interact directly or indirectly with the RNA polymerase II-initiation complex to activate transcription was investigated by in vivo transcription interference ("squelching") experiments. Coexpression of a Jun mutant lacking its DNA binding domain strongly represses the activity of wild-type c-Jun. Repression depends on the presence of the transactivation domains (TADs), suggesting that a limiting factor interacting with the TADs is essential to link Jun and the components of the transcriptional machinery. The activity of this intermediary factor(s) is restricted to TADs characterized by an abundance of negatively charged amino acids, as demonstrated by the abilities of the TADs of JunB, GAL4, and VP16 to repress c-Jun activity. Depending on the presence of the TADs of Jun, we found physical interaction between Jun and a cluster of three proteins with molecular masses of 52, 53, and 54 kDa (p52/54). Association between Jun and p52/54 is strongly reduced in the presence of VP16, suggesting that the two proteins compete for binding to p52/54. Transcription factors containing a different type of TAD (e.g., GHF1, estrogen receptor, or serum response factor) fail to inhibit Jun activity, suggesting that these proteins act through a different mechanism. We consider the requirement of Jun to interact with p52/54 utilized by other transcription factors a new mechanism in the regulation of transcription of Jun-dependent target genes. PMID- 1448083 TI - A REB1-binding site is required for GCN4-independent ILV1 basal level transcription and can be functionally replaced by an ABF1-binding site. AB - The ILV1 gene of Saccharomyces cerevisiae encodes the first committed step in isoleucine biosynthesis and is regulated by general control of amino acid biosynthesis. Deletion analysis of the ILV1 promoter revealed a GC-rich element important for the basal level expression. This cis-acting element, called ILV1BAS, is functional independently of whether GCN4 protein is present. Furthermore, unlike the situation at HIS4, the magnitude of GCN4-mediated derepression is independent of ILV1BAS. The element has homology to the consensus REB1-binding sequence CGGGTARNNR. Gel retardation assays showed that REB1 binds specifically to this element. We show that REB1-binding sites normally situated in the SIN3 promoter and in the 35S rRNA promoter can substitute for the ILV1 REB1 site. Furthermore, a SIN3 REB1 site containing a point mutation that abolishes REB1 binding does not support ILV1 basal level expression, suggesting that binding of REB1 is important for the control of ILV1 basal level expression. Interestingly, an ABF1-binding site can also functionally replace the ILV1 REB1 binding site. A mutated ABF1 site that displays a very low affinity for ABF1 does not functionally replace the ILV1 REB1 site. This suggests that ABF1 and REB1 may have related functions within the cell. Although the REB1-binding site is required for the ILV1 basal level expression, the site on its own stimulates transcription only slightly when combined with the CYC1 downstream promoter elements, indicating that another ILV1 promoter element functions in combination with the REB1 site to control high basal level expression. PMID- 1448084 TI - A mammalian cell line deficient in activity of the DNA repair enzyme 5 hydroxymethyluracil-DNA glycosylase is resistant to the toxic effects of the thymidine analog 5-hydroxymethyl-2'-deoxyuridine. AB - We isolated a mutant mammalian cell line lacking activity for the DNA repair enzyme 5-hydroxymethyluracil-DNA glycosylase (HmUra-DNA glycosylase). The mutant was isolated through its resistance to the thymidine analog 5-hydroxymethyl-2' deoxyuridine (HmdUrd). The mutant incorporates HmdUrd into DNA to the same extent as the parent line but, lacking the repair enzyme, does not remove it. The phenotype of the mutant demonstrates that the toxicity of HmdUrd does not result from substitution of thymine in DNA by HmUra but rather from the removal via base excision of large numbers of HmUra residues in DNA. This finding elucidates a novel mechanism of toxicity for a xenobiotic nucleoside. Furthermore, the isolation of this line supports our hypothesis that the enzymatic repairability of HmUra derives not from its formation opposite adenine via the oxidation of thymine, but rather from its formation opposite guanine as a product of the oxidation and subsequent deamination of 5-methylcytosine. PMID- 1448085 TI - Osteoblast-specific expression of growth hormone stimulates bone growth in transgenic mice. AB - Growth hormone (GH) is an important regulator of postnatal growth, acting on a wide variety of target tissues. Here, we show that local production of GH in osteoblasts is able to stimulate bone growth directly without significant systemic effects. Mice were made transgenic by microinjection of an osteocalcin human GH (osteocalcin-hGH) gene construct in which approximately 1,800 bp of the rat osteocalcin promoter was fused to the hGH gene. Five lines of transgenic mice, each with measurable amounts of serum hGH (ranging from 1 to 1,000 ng/ml), were analyzed. Northern (RNA) blot hybridization showed that the hGH transcript was detectable only in the bone. Further characterization of hGH mRNA distribution by in situ hybridization revealed that in neonates the most intense signal was found in periosteal osteoblasts, while in adults, trabecular and endosteal osteoblasts were favored. In one transgenic line (992-1), hGH was expressed at a much lower level and had minimal systemic effects; however, the local concentrations of hGH in bone were sufficient to stimulate bone growth in these animals. PMID- 1448086 TI - Isolation and structural analysis of a 1.2-megabase N-myc amplicon from a human neuroblastoma. AB - Oncogene amplification is observed frequently in human cancers, but little is known about the mechanism of gene amplification or the structure of amplified DNA in tumor cells. We have studied the N-myc amplified domain from a representative neuroblastoma cell line, SMS-KAN, and compared the map of the amplicon in this cell line with that seen in normal DNA. The SMS-KAN cell line DNA was cloned into yeast artificial chromosomes (YACs), and clones were identified by screening the YAC library with amplified DNA probes that were obtained previously (B. Zehnbauer, D. Small, G. M. Brodeur, R. Seeger, and B. Vogelstein, Mol. Cell. Biol. 8:522-530, 1988). In addition, YAC clones corresponding to the normal N-myc locus on chromosome 2 were obtained by screening two normal human YAC libraries with these probes, and the restriction maps of the two sets of overlapping YACs were compared. Our results suggest that the amplified domain in this cell line is a approximately 1.2-Mb circular molecule with a head-to-tail configuration, and the physical map of the normal N-myc locus generally is conserved in the amplicon. These results provide a physical map of the amplified domain of a neuroblastoma cell line that has de novo amplification of an oncogene. The head to-tail organization, the general conservation of the normal physical map in the amplicon, and the extrachromosomal location of the amplified DNA are most consistent with the episome formation-plus-segregation mechanism of gene amplification in these tumors. PMID- 1448087 TI - The fission yeast genes pyp1+ and pyp2+ encode protein tyrosine phosphatases that negatively regulate mitosis. AB - We have used degenerate oligonucleotide probes based on sequences conserved among known protein tyrosine phosphatases (PTPases) to identify two Schizosaccharomyces pombe genes encoding PTPases. We previously described the cloning of pyp1+ (S. Ottilie, J. Chernoff, G. Hannig, C. S. Hoffman, and R. L. Erikson, Proc. Natl. Acad. Sci. USA 88:3455-3459, 1991), and here we describe a second gene, called pyp2+. The C terminus of each protein contains sequences conserved in the apparent catalytic domains of all known PTPases. Disruption of pyp2+ results in viable cells, as was the case for pyp1+, whereas disruption of pyp2+ and pyp1+ results in synthetic lethality. Overexpression of either pyp1+ or pyp2+ in wild type strains leads to a delay in mitosis but is suppressed by a wee1-50 mutation at 35 degrees C or a cdc2-1w mutation. A pyp1 disruption suppresses the temperature-sensitive lethality of a cdc25-22 mutation. Our data suggest that pyp1+ and pyp2+ act as negative regulators of mitosis upstream of the wee1+/mik1+ pathway. PMID- 1448088 TI - Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding. AB - Mutations in the p53 gene are most frequent in cancer. Many p53 mutants possess transforming activity in vitro. In cells transformed by such mutants, the mutant protein is oligomerized with endogenous cell p53. To determine the relevance of oligomerization for transformation, miniproteins containing C-terminal portions of p53 were generated. These miniproteins, although carrying no point mutation, transformed at least as efficiently as full-length mutant p53. Transforming activity was coupled with the ability to oligomerize with wild-type p53, as well as with the ability to abrogate sequence-specific DNA binding by coexpressed wild type p53. These findings suggest that p53-mediated transformation may operate through a dominant negative mechanism, involving the generation of DNA binding incompetent oligomers. PMID- 1448089 TI - Alternative topogenic signals in peroxisomal citrate synthase of Saccharomyces cerevisiae. AB - The tripeptide serine-lysine-leucine (SKL) occurs at the carboxyl terminus of many peroxisomal proteins and serves as a peroxisomal targeting signal. Saccharomyces cerevisiae has two isozymes of citrate synthase. The peroxisomal form, encoded by CIT2, terminates in SKL, while the mitochondrial form, encoded by CIT1, begins with an amino-terminal mitochondrial signal sequence and ends in SKN. We analyzed the importance of SKL as a topogenic signal for citrate synthase, using oleate to induce peroxisomes and density gradients to fractionate organelles. Our experiments revealed that SKL was necessary for directing citrate synthase to peroxisomes. C-terminal SKL was also sufficient to target a leaderless version of mitochondrial citrate synthase to peroxisomes. Deleting this tripeptide from the CIT2 protein caused peroxisomal citrate synthase to be missorted to mitochondria. These experiments suggest that the CIT2 protein contains a cryptic mitochondrial targeting signal. PMID- 1448090 TI - Identification of a cysteine-rich receptor for fibroblast growth factors. AB - The fibroblast growth factor (FGF) family consists of seven members whose activities are thought to be mediated by multiple receptors. Here we describe the cDNA cloning, expression, and characterization of a cysteine-rich FGF receptor (CFR) that is distinct from previously identified FGF receptors. The deduced amino acid sequence for CFR suggests that it is an integral membrane protein containing a large extracellular domain comprising 16 cysteine-rich repeated units and an intracellular domain of 13 amino acids. No reported sequences exhibit significant homologies to either the repeated extracellular motif or to the entire CFR amino acid sequence. Several CFR transcripts are present in embryonic chick tissue, suggesting that CFR undergoes alternate mRNA splicing or that related genes are present. Chinese hamster ovary cells transfected with the CFR cDNA express a 150-kDa polypeptide that binds FGF-1, FGF-2, and FGF-4 but does not bind several non-FGF family members. The high degree of evolutionary conservation among vertebrate CFRs and its ability to bind three different FGFs with high affinity suggest that this unique receptor plays an important role in FGF biology. PMID- 1448091 TI - Activation of the HLA-DRA gene in primary human T lymphocytes: novel usage of TATA and the X and Y promoter elements. AB - Human T lymphocytes express human leukocyte antigen (HLA)-DR-alpha (DRA) upon mitogenic or antigenic stimulation. DR+ T cells are also found in a number of inflammatory and autoimmune diseases and have a proposed role in these diseases. The molecular mechanism of DR regulation in untransformed blood T lymphocytes was studied here by transient transfection of DRA-chloramphenicol acetyltransferase reporter gene constructs. Several novel features of this regulation were observed. During the early stages of T-cell activation by mitogens or antigens, strong promoter induction was exhibited with the proximal 43 bp of the DRA promoter which contains a TATTA motif. Addition of upstream X and Y DNA elements augmented the response. This contrasts with data from transformed cell lines in which the proximal 43 bp produced no detectable promoter function, and the inclusion of X and Y elements is essential for basal level expression. Mutation of the TATTA motif or substitution with a functional but different TATA element produced errant initiation and greatly reduced gene expression. Interestingly, T lymphocytes from a normal donor were DR+ prior to in vitro stimulation, and again, strong promoter activity was observed with 43 bp of proximal sequence. Unexpectedly, the presence of the X and Y elements correlated with a suppression of class II promoter function and surface antigen expression. This study of nontransformed lymphocytes reveals several novel features of DRA gene regulation and underscores the value and necessity of such studies. PMID- 1448093 TI - Cloning and characterization of SRP1, a suppressor of temperature-sensitive RNA polymerase I mutations, in Saccharomyces cerevisiae. AB - The SRP1-1 mutation is an allele-specific dominant suppressor of temperature sensitive mutations in the zinc-binding domain of the A190 subunit of Saccharomyces cerevisiae RNA polymerase I (Pol I). We found that it also suppresses temperature-sensitive mutations in the zinc-binding domain of the Pol I A135 subunit. This domain had been suggested to be in physical proximity to the A190 zinc-binding domain. We have cloned the SRP1 gene and determined its nucleotide sequence. The gene encodes a protein of 542 amino acids consisting of three domains: the central domain, which is composed of eight (degenerate) 42 amino-acid contiguous tandem repeats, and the surrounding N-terminal and C terminal domains, both of which contain clusters of acidic and basic amino acids and are very hydrophilic. The mutational alteration (P219Q) responsible for the suppression was found to be in the central domain. Using antibody against the SRP1 protein, we have found that SRP1 is mainly localized at the periphery of the nucleus, apparently more concentrated in certain regions, as suggested by a punctate pattern in immunofluorescence microscopy. We suggest that SRP1 is a component of a larger macromolecular complex associated with the nuclear envelope and interacts with Pol I either directly or indirectly through other components in the structure containing SRP1. PMID- 1448092 TI - Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F. AB - The retinoblastoma protein interacts with a number of cellular proteins to form complexes which are probably crucial for its normal physiological function. To identify these proteins, we isolated nine distinct clones by direct screening of cDNA expression libraries using purified RB protein as a probe. One of these clones, Ap12, is expressed predominantly at the G1-S boundary and in the S phase of the cell cycle. The nucleotide sequence of Ap12 has features characteristic of transcription factors. The C-terminal region binds to unphosphorylated RB in regions similar to those to which T antigen binds and contains a transactivation domain. A region containing a potential leucine zipper flanked by basic residues is able to bind an E2F recognition sequence specifically. Expression of Ap12 in mammalian cells significantly enhances E2F-dependent transcriptional activity. These results suggest that Ap12 encodes a protein with properties known to be characteristic of transcription factor E2F. PMID- 1448094 TI - Separate information required for nuclear and subnuclear localization: additional complexity in localizing an enzyme shared by mitochondria and nuclei. AB - The TRM1 gene of Saccharomyces cerevisiae codes for a tRNA modification enzyme, N2,N2-dimethylguanosine-specific tRNA methyltransferase (m2(2)Gtase), shared by mitochondria and nuclei. Immunofluorescent staining at the nuclear periphery demonstrates that m2(2)Gtase localizes at or near the nuclear membrane. In determining sequences necessary for targeting the enzyme to nuclei and mitochondria, we found that information required to deliver the enzyme to the nucleus is not sufficient for its correct subnuclear localization. We also determined that mislocalizing the enzyme from the nucleus to the cytoplasm does not destroy its biological function. This change in location was caused by altering a sequence similar to other known nuclear targeting signals (KKSKKKRC), suggesting that shared enzymes are likely to use the same import pathway as proteins that localize only to the nucleus. As with other well-characterized mitochondrial proteins, the mitochondrial import of the shared methyltransferase depends on amino-terminal amino acids, and removal of the first 48 amino acids prevents its import into mitochondria. While this truncated protein is still imported into nuclei, the immunofluorescent staining is uniform throughout rather than at the nuclear periphery, a staining pattern identical to that described for a fusion protein consisting of the first 213 amino acids of m2(2)Gtase in frame with beta-galactosidase. As both of these proteins together contain the entire m2(2)Gtase coding region, the information necessary for association with the nuclear periphery must be more complex than the short linear sequence necessary for nuclear localization. PMID- 1448095 TI - Repression and activation of the Drosophila dopa decarboxylase gene in glia. AB - Glial expression of the Drosophila dopa decarboxylase gene (Ddc) is repressed by a regulatory region located approximately 1 kb upstream of the transcriptional start site. We have used in vitro mutagenesis and germ line transformation to determine which elements within the Ddc promoter mediate repression. Our evidence suggests that the hypodermal cell activator elements IIA and IIB play a major role in the transcriptional regulation of Ddc in glial cells. A variety of mutations demonstrate that element IIA is a strong glial activator element and that element IIB is necessary for glial repression. Although these two regulatory elements are nearly identical in sequence, our data suggest that they are not redundant. Altering the wild-type number and spacing of elements IIA and IIB indicates that the wild-type arrangement of this repeat is critical for repression. We conclude that these key elements of the Ddc promoter regulate both activation and repression in glia. PMID- 1448096 TI - A novel DNA-binding motif abuts the zinc finger domain of insect nuclear hormone receptor FTZ-F1 and mouse embryonal long terminal repeat-binding protein. AB - Fruit fly FTZ-F1, silkworm BmFTZ-F1, and mouse embryonal long terminal repeat binding protein are members of the nuclear hormone receptor superfamily, which recognizes the same sequence, 5'-PyCAAGGPyCPu-3'. Among these proteins, a 30 amino-acid basic region abutting the C-terminal end of the zinc finger motif, designated the FTZ-F1 box, is conserved. Gel mobility shift competition by various mutant peptides of the DNA-binding region revealed that the FTZ-F1 box as well as the zinc finger motif is involved in the high-affinity binding of FTZ-F1 to its target site. Using a gel mobility shift matrix competition assay, we demonstrated that the FTZ-F1 box governs the recognition of the first three bases, while the zinc finger region recognizes the remaining part of the binding sequence. We also showed that the DNA-binding region of FTZ-F1 recognizes and binds to DNA as a monomer. Occurrence of the FTZ-F1 box sequence in other members of the nuclear hormone receptor superfamily raises the possibility that these receptors constitute a unique subfamily which binds to DNA as a monomer. PMID- 1448097 TI - Sequence of cDNA comprising the human pur gene and sequence-specific single stranded-DNA-binding properties of the encoded protein. AB - The human Pur factor binds strongly to a sequence element repeated within zones of initiation of DNA replication in several eukaryotic cells. The protein binds preferentially to the purine-rich single strand of this element, PUR. We report here the cloning and sequencing of a cDNA encoding a protein with strong affinity for the PUR element. Analysis with a series of mutated oligonucleotides defines a minimal single-stranded DNA Pur-binding element. The expressed Pur open reading frame encodes a protein of 322 amino acids. This protein, Pur alpha, contains three repeats of a consensus motif of 23 amino acids and two repeats of a second consensus motif of 26 amino acids. Near its carboxy terminus, the protein possesses an amphipathic alpha-helix and a glutamine-rich domain. The repeat region of Pur cDNA is homologous to multiple mRNA species in each of several human cell lines and tissues. The HeLa cDNA library also includes a clone encoding a related gene, Pur beta, containing a version of the 23-amino-acid consensus motif similar, but not identical, to those in Pur alpha. Results indicate a novel type of modular protein with capacity to bind repeated elements in single-stranded DNA. PMID- 1448098 TI - The EGD1 product, a yeast homolog of human BTF3, may be involved in GAL4 DNA binding. AB - A variety of techniques, including filter binding, footprinting, and gel retardation, can be used to assay the transcriptional activator GAL4 (Gal4p) through the initial steps of its purification from yeast cells. Following DNA affinity chromatography, Gal4p still bound DNA selectively when assayed by filter binding or footprinting. However, the affinity-purified protein was no longer capable of forming a stable complex with DNA, as assayed by gel retardation. Mixing the purified Gal4p with the flowthrough fraction from the DNA affinity column restored gel retardation complex formation. Gel retardation assays were used to monitor the purification of a heat-stable Gal4p-DNA complex stabilization activity from the affinity column flowthrough. The activity coeluted from the final purification step with polypeptides of 21 and 27 kDa. The yeast gene encoding the 21-kDa protein was cloned on the basis of its N-terminal amino acid sequence. The gene, named EGD1 (enhancer of GAL4 DNA binding), encodes a highly basic protein (21% lysine and arginine) with a predicted molecular mass of 16.5 kDa. The amino acid sequence of the EGD1 product, Egd1p, is highly similar to that of the human protein BTF3 (X. M. Zheng, D. Black, P. Chambon, and J. M. Egly, Nature [London] 344:556-559, 1990). Although an egd1 null mutant was viable and Gal+, induction of the galactose-regulated genes in the egd1 mutant strain was significantly reduced when cells were shifted from glucose to galactose. PMID- 1448099 TI - Yeast RHO3 and RHO4 ras superfamily genes are necessary for bud growth, and their defect is suppressed by a high dose of bud formation genes CDC42 and BEM1. AB - RHO3 and RHO4 are members of the ras superfamily genes of the yeast Saccharomyces cerevisiae and are related functionally to each other. Experiments using a conditionally expressed allele of RHO4 revealed that depletion of both the RHO3 and RHO4 gene products resulted in lysis of cells with a small bud, which could be prevented by the presence of osmotic stabilizing agents in the medium. rho3 rho4 cells incubated in medium containing an osmotic stabilizing agent were rounded and enlarged and displayed delocalized deposition of chitin and delocalization of actin patches, indicating that these cells lost cell polarity. Nine genes whose overexpression could suppress the defect of the RHO3 function were isolated (SRO genes). Two of them were identical with CDC42 and BEM1, bud site assembly genes involved in the process of bud emergence. A high dose of CDC42 complemented the rho3 defect, whereas overexpression of RHO3 had an inhibitory effect on the growth of mutants defective in the CDC24-CDC42 pathway. These results, along with comparison of cell morphology between rho3 rho4 cells and cdc24 (or cdc42) mutant cells kept under the restrictive conditions, strongly suggest that the functions of RHO3 and RHO4 are required after initiation of bud formation to maintain cell polarity during maturation of daughter cells. PMID- 1448101 TI - Evidence that POB1, a Saccharomyces cerevisiae protein that binds to DNA polymerase alpha, acts in DNA metabolism in vivo. AB - Potential DNA replication accessory factors from the yeast Saccharomyces cerevisiae have previously been identified by their ability to bind to DNA polymerase alpha protein affinity matrices (J. Miles and T. Formosa, Proc. Natl. Acad. Sci. USA 89:1276-1280, 1992). We have now used genetic methods to characterize the gene encoding one of these DNA polymerase alpha-binding proteins (POB1) to determine whether it plays a role in DNA replication in vivo. We find that yeast cells lacking POB1 are viable but display a constellation of phenotypes indicating defective DNA metabolism. Populations of cells lacking POB1 accumulate abnormally high numbers of enlarged large-budded cells with a single nucleus at the neck of the bud. The average DNA content in a population of cells lacking POB1 is shifted toward the G2 value. These two phenotypes indicate that while the bulk of DNA replication is completed without POB1, mitosis is delayed. Deleting POB1 also causes elevated levels of both chromosome loss and genetic recombination, enhances the temperature sensitivity of cells with mutant DNA polymerase alpha genes, causes increased sensitivity to UV radiation in cells lacking a functional RAD9 checkpoint gene, and causes an increased probability of death in cells carrying a mutation in the MEC1 checkpoint gene. The sequence of the POB1 gene indicates that it is identical to the CTF4 (CHL15) gene identified previously in screens for mutations that diminish the fidelity of chromosome transmission. These phenotypes are consistent with defective DNA metabolism in cells lacking POB1 and strongly suggest that this DNA polymerase alpha-binding protein plays a role in accurately duplicating the genome in vivo. PMID- 1448100 TI - Molecular cloning of casein kinase II alpha subunit from Dictyostelium discoideum and its expression in the life cycle. AB - A Dictyostelium discoideum cDNA encoding an alpha-type subunit of casein kinase II was isolated, and its cDNA was used to study developmental expression of casein kinase II during the Dictyostelium life cycle. The 1.3-kb cDNA insert contained an open reading frame of 337 amino acids (M(r) 39,900). The deduced amino acid sequence has high homology with those of casein kinase II alpha subunits from other species. Genomic Southern blot analysis suggested that there is a single gene encoding casein kinase II alpha subunit in D. discoideum. Northern (RNA) blot analysis showed that the casein kinase II alpha-subunit gene is expressed constitutively as a 1.9-kb mRNA throughout vegetative growth and multicellular development. Casein kinase purified from normal vegetative cells contained a major protein band of approximately 36 kDa, which was recognized by antisera raised against rat testis casein kinase II. Comparison of the in vitro transcription/translation product of the alpha-subunit cDNA clone and the purified 36-kDa protein by partial proteolysis indicated that the isolated cDNA clone encodes the Dictyostelium casein kinase II alpha subunit. No protein corresponding to a beta subunit was detected in purified casein kinase. Immunoblot analysis using anti-rat casein kinase II sera showed that the alpha subunit of casein kinase II is expressed constitutively like its mRNA during the life cycle of D. discoideum. Casein kinase II activity measured by using a specific peptide substrate paralleled the level of alpha subunit detected by immunoblotting during the life cycle, with a maximum variation of approximately 2 fold. We were unable to obtain disruptants of the casein kinase II alpha gene, suggesting that there is a single casein kinase II alpha gene, which is essential for vegetative growth of D. discoideum. PMID- 1448102 TI - Two cellular proteins bind specifically to a purine-rich sequence necessary for the destabilization function of a c-fos protein-coding region determinant of mRNA instability. AB - The c-fos proto-oncogene mRNA is rapidly degraded within minutes after its appearance in the cytoplasm of growth factor-stimulated mammalian fibroblasts. At least two functionally independent sequence elements are responsible for the lability of c-fos mRNA. One of these determinants is located within a 0.32-kb sequence present in the protein-coding region. We demonstrate by gel mobility shift experiments and UV cross-linking that at least two protein factors specifically interact with a 56-nucleotide purine-rich sequence located at the 5' end of the 0.32-kb coding region determinant of mRNA instability (CRDI). One protein is predominantly associated with the polysomes, while the other is detected in the post-ribosomal supernatant. Sequence comparison of members of the fos gene family revealed that the high purine content of the protein-binding region is conserved through evolution. Deletion of this region from the 0.32-kb CRDI severely impedes its function as an RNA-destabilizing element. Our results suggest that binding of the two proteins to the purine-rich sequence may participate in the rapid mRNA decay mediated by this 0.32-kb c-fos CRDI. PMID- 1448103 TI - A mutation outside the two zinc fingers of ADR1 can suppress defects in either finger. AB - A second-site mutation that restored DNA binding to ADR1 mutants altered at different positions in the two zinc fingers was identified. This mutation (called IS1) was a conservative change of arginine 91 to lysine in a region amino terminal to the two zinc fingers and known from previous experiments to be necessary for DNA binding. IS1 increased binding to the UAS1 sequence two- to sevenfold for various ADR1 mutants and twofold for wild-type ADR1. The change of arginine 91 to glycine decreased binding twofold, suggesting that this arginine is involved in DNA binding in the wild-type protein. The increase in binding by IS1 did not involve protein-protein interactions between the two ADR1 monomers, nor did it require the presence of the sequences flanking UAS1. However, the effect of IS1 was influenced by the sequence of the first finger, suggesting that interactions between the region amino terminal to the fingers and the fingers themselves could exist. A model for the role of the amino-terminal region based on these results and sequence homologies with other DNA-binding motifs is proposed. PMID- 1448104 TI - P25 gene regulation in Bombyx mori silk gland: two promoter-binding factors have distinct tissue and developmental specificities. AB - The gene encoding the silk protein P25 is expressed in the posterior silk gland of Bombyx mori with strict territorial and developmental specificities. The cis acting regulatory elements previously located within the 441-bp 5' proximal sequence of the gene were examined for protein-binding capacities. We identified two factors, BMFA and SGFB, that lead to prominent band shifts and the target sites for which are included in a region homologous to the fibroin gene enhancer sequence. Analysis of the tissue-specific incidence of both factors showed that BMFA is ubiquitous, whereas SGFB is restricted to the silk gland cells. However, SGFB was found in both posterior and middle silk gland cells and therefore likely directs organ-specific, but not territory-specific, expression. Developmental studies throughout the fourth larval molt, at which the P25 gene status changes from derepressed to repressed, revealed that BMFA is reversibly modified at the transition from intermolt to molt. Indeed, the preexisting BMFA is replaced by a structurally related factor, BMFA', during the 2 h following head capsule apolysis. The exact temporal coincidence of this conversion with the onset of gene repression suggests that BMFA' is involved in transcription inactivation and likely results from a transduction process initiated by the hormonal change at molting. PMID- 1448105 TI - A mutation in the tRNA nucleotidyltransferase gene promotes stabilization of mRNAs in Saccharomyces cerevisiae. AB - To identify trans-acting factors involved in mRNA decay in the yeast Saccharomyces cerevisiae, we have begun to characterize conditional lethal mutants that affect mRNA steady-state levels. A screen of a collection of temperature-sensitive mutants identified ts352, a mutant that accumulated moderately stable and unstable mRNAs after a shift from 23 to 37 degrees C (M. Aebi, G. Kirchner, J.-Y. Chen, U. Vijayraghavan, A. Jacobson, N.C. Martin, and J. Abelson, J. Biol. Chem. 265:16216-16220, 1990). ts352 has a defect in the CCA1 gene, which codes for tRNA nucleotidyltransferase, the enzyme that adds 3' CCA termini to tRNAs (Aebi et al., J. Biol. Chem., 1990). In a shift to the nonpermissive temperature, ts352 (cca1-1) cells rapidly cease protein synthesis, reduce the rates of degradation of the CDC4, TCM1, and PAB1 mRNAs three- to fivefold, and increase the relative number of ribosomes associated with mRNAs and the overall size of polysomes. These results were analogous to those observed for cycloheximide-treated cells and are generally consistent with models that invoke a role for translational elongation in the process of mRNA turnover. PMID- 1448106 TI - Multiple mechanisms of interference between transformation and differentiation in thyroid cells. AB - Transformation of the thyroid cell line FRTL-5 results in loss or reduction of differentiation as measured by the expression of thyroglobulin and thyroperoxidase, two proteins whose genes are exclusively expressed in thyroid follicular cells. The biochemical mechanisms leading to this phenomenon were investigated in three cell lines obtained by transformation of FRTL-5 cells with Ki-ras, Ha-ras, and polyomavirus middle-T oncogenes. With the ras oncogenes, transformation leads to undetectable expression of the thyroglobulin and thyroperoxidase genes. However, the mechanisms responsible for the extinction of the differentiated phenotype seem to be different for the two ras oncogenes. In Ki-ras-transformed cells, the mRNA encoding TTF-1, a transcription factor controlling thyroglobulin and thyroperoxidase gene expression, is severely reduced. On the contrary, nearly wild-type levels of TTF-1 mRNA are detected in Ha-ras-transformed cells. Furthermore, overexpression of TTF-1 can activate transcription of the thyroglobulin promoter in Ki-ras-transformed cells, whereas it has no effect on thyroglobulin transcription in the Ha-ras-transformed line. Expression of polyoma middle-T antigen in thyroid cells leads to only a reduction of differentiation and does not severely affect either the activity or the amount of TTF-1. Another thyroid cell-specific transcription factor, TTF-2, is more sensitive to transformation, since it disappears in all three transformed lines, and probably contributes to the reduced expression of the differentiated phenotype. PMID- 1448107 TI - Mutations activating the yeast eIF-2 alpha kinase GCN2: isolation of alleles altering the domain related to histidyl-tRNA synthetases. AB - The protein kinase GCN2 stimulates expression of the yeast transcriptional activator GCN4 at the translational level by phosphorylating the alpha subunit of translation initiation factor 2 (eIF-2 alpha) in amino acid-starved cells. Phosphorylation of eIF-2 alpha reduces its activity, allowing ribosomes to bypass short open reading frames present in the GCN4 mRNA leader and initiate translation at the GCN4 start codon. We describe here 17 dominant GCN2 mutations that lead to derepression of GCN4 expression in the absence of amino acid starvation. Seven of these GCN2c alleles map in the protein kinase moiety, and two in this group alter the presumed ATP-binding domain, suggesting that ATP binding is a regulated aspect of GCN2 function. Six GCN2c alleles map in a region related to histidyl-tRNA synthetases, and two in this group alter a sequence motif conserved among class II aminoacyl-tRNA synthetases that directly interacts with the acceptor stem of tRNA. These results support the idea that GCN2 kinase function is activated under starvation conditions by binding uncharged tRNA to the domain related to histidyl-tRNA synthetase. The remaining GCN2c alleles map at the extreme C terminus, a domain required for ribosome association of the protein. Representative mutations in each domain were shown to depend on the phosphorylation site in eIF-2 alpha for their effects on GCN4 expression and to increase the level of eIF-2 alpha phosphorylation in the absence of amino acid starvation. Synthetic GCN2c double mutations show greater derepression of GCN4 expression than the parental single mutations, and they have a slow-growth phenotype that we attribute to inhibition of general translation initiation. The phenotypes of the GCN2c alleles are dependent on GCN1 and GCN3, indicating that these two positive regulators of GCN4 expression mediate the inhibitory effects on translation initiation associated with activation of the yeast eIF-2 alpha kinase GCN2. PMID- 1448108 TI - The SH2/SH3 domain-containing protein Nck is recognized by certain anti phospholipase C-gamma 1 monoclonal antibodies, and its phosphorylation on tyrosine is stimulated by platelet-derived growth factor and epidermal growth factor treatment. AB - In the course of our investigation of phospholipase C (PLC)-gamma 1 phosphorylation by using a set of anti-PLC-gamma 1 monoclonal antibodies (P.-G. Suh, S. H. Ryu, W. C. Choi, K.-Y. Lee, and S. G. Rhee, J. Biol. Chem. 263:14497 14504, 1988), we found that some of these antibodies directly recognize a 47-kDa protein. We show here that this 47-kDa protein is identical to the SH2/SH3 containing protein Nck (J. M. Lehmann, G. Riethmuller, and J. P. Johnson, Nucleic Acids Res. 18:1048, 1990). Nck was found to be constitutively phosphorylated on serine in resting NIH 3T3 cells. Platelet-derived growth factor (PDGF) treatment led to increased Nck phosphorylation on both tyrosine and serine. Nck was also found to be phosphorylated on tyrosine in epidermal growth factor (EGF)-treated A431 cells and in v-Src-transformed NIH 3T3 cells. Multiple sites of serine phosphorylation were detected in Nck from resting cells, and no novel sites were found upon PDGF or EGF treatment. A single major tyrosine phosphorylation site was found in Nck in both PDGF- and EGF-treated cells and in v-Src-transformed cells. This same tyrosine was phosphorylated in vitro by purified PDGF and EGF receptors and also by pp60c-src. We compared the phosphorylation of Nck and PLC gamma 1 in several cell lines transformed by oncogenes with different modes of transformation. Although PLC-gamma 1 and Nck have significant amino acid identity, particularly in their SH3 regions, and both associate with growth factor receptors in a ligand-dependent manner, they were not always phosphorylated on tyrosine in a coincident manner. PMID- 1448109 TI - Characterization of complementary DNA encoding the rat neuromedin U precursor. AB - Neuromedin U (NmU), a peptide originally isolated from porcine spinal cord, is known for its ability to stimulate uterine smooth muscle contraction and to cause selective vasoconstriction. It was subsequently isolated from a number of species. Among the species studied, the five amino acids at the C-terminus of the peptide are totally conserved, suggesting that this region is of major importance. We have cloned and sequenced the cDNA encoding the rat NmU precursor protein using the anchor polymerase chain reaction technique. Sequence analysis revealed that NmU is synthesized as a 174-amino acid precursor. Like the precursors of most other small regulatory peptides, it has a hydrophobic signal peptide and a number of paired dibasic amino acids, which may serve as signals for enzymatic cleavage, to release NmU and a series of other peptides. These predicted flanking peptides of NmU show no significant homology with entries in the protein databases searched, and the cDNA likewise shows no homology with entries in the GenBank database. Northern blot analysis using total RNA extracted from different rat tissues shows high levels of NmU mRNA in the ileum, thyroid, and anterior pituitary. Southern blot analysis of rat genomic DNA demonstrates that NmU is a single copy gene. PMID- 1448110 TI - Structural and functional analysis of the insulin-like growth factor I receptor gene promoter. AB - The insulin-like growth factor I receptor (IGF-I-R) gene is expressed in most body tissues. The levels of IGF-I-R mRNA, however, are regulated by a number of physiological conditions (development, differentiation, and hormonal milieu) as well as in certain pathological states (diabetes and tumors). To understand the molecular mechanisms which control the transcription of the IGF-I-R gene, we have cloned the promoter of the rat receptor gene and have characterized its activity by transient expression assays. Different fragments of the 5'-flanking region (subcloned upstream of a luciferase reporter gene) were transfected into buffalo rat liver 3A cells (a cell line with a low number of IGF-I binding sites) and Chinese hamster ovary cells (a cell line with a higher number of cell-surface receptors). In both cell lines, most of the promoter activity was located in the proximal 416 base pairs of 5'-flanking region. However, further dissection of this proximal fragment revealed a cell type-specific pattern of promoter activity. Thus, in buffalo rat liver 3A cells, subfragments of this region each contributed to total activity, suggesting that contiguous cis-elements can act together to activate transcription. In Chinese hamster ovary cells, on the other hand, subfragments of the proximal promoter region partially substituted for the proximal 416 base pairs of 5'-flanking region. Coexpression studies using an IGF I-R promoter reporter construct together with an Sp1 expression vector (under the control of an ADH promoter) were performed in SL2 cells, a Drosophila cell line which lacks endogenous Sp1. The results obtained showed that Sp1 can trans activate the IGF-I-R promoter in vivo. Transient transfection assays were complemented with gel-retardation assays and DNase I footprinting experiments, which showed that transcription factor Sp1 is potentially an important regulator of IGF-I-R gene expression. PMID- 1448111 TI - Testicular expression of PC4 in the rat: molecular diversity of a novel germ cell specific Kex2/subtilisin-like proprotein convertase. AB - The rat cDNA sequence of PC4 (rPC4), representing a new member of the Kex2/subtilisin-like proprotein convertases, demonstrated the presence of at least three rPC4 mRNAs resulting in the production of rPC4-A (654 amino acids), rPC4-B (619 amino acids), and rPC4-C (609 amino acids) with different C-terminal sequences. Analogous to rat PC4, three cDNAs were also found for the mouse PC4. The observed molecular diversity of PC4 mRNA possibly results from the differential splicing and/or exon skipping of the parent gene. PC4 mRNA, with a major form at 2.8 kilobases, was highly abundant in the rat testis but could not be detected by Northern analysis in any other tissues including the central nervous system and peripheral tissues. Testicular cell separation studies combined with Northern analysis indicate the high expression levels of PC4 in germ cells but not in Leydig, Sertoli, or peritubular cells. In situ hybridization histochemistry confirms the site of PC4 gene expression as the pachytene spermatocytes and the round spermatids but not in the elongating spermatids. We also demonstrate the colocalization of PC4 with proenkephalin in testicular germ cells by in situ hybridization. A study of the ontogeny of PC4 indicated that PC4 mRNA was first expressed postnatally between days 19 and 22, coinciding with the first stages of spermiogenesis. The stage-specific expression of PC4 in testis indicates its potential role in the developmental maturation of germ cells and that this convertase may play a specific physiological function in reproduction. PMID- 1448112 TI - The multifunctional peptidylglycine alpha-amidating monooxygenase gene: exon/intron organization of catalytic, processing, and routing domains. AB - Peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3) is a multifunctional protein containing two enzymes that act sequentially to catalyze the alpha-amidation of neuroendocrine peptides. Peptidylglycine alpha hydroxylating monooxygenase (PHM) catalyzes the first step of the reaction and is dependent on copper, ascorbate, and molecular oxygen. Peptidyl-alpha hydroxyglycine alpha-amidating lyase (PAL) catalyzes the second step of the reaction. Previous studies demonstrated that alternative splicing results in the production of bifunctional PAM proteins that are integral membrane or soluble proteins as well as soluble monofunctional PHM proteins. Rat PAM is encoded by a complex single copy gene that consists of 27 exons and encompasses more than 160 kilobases (kb) of genomic DNA. The 12 exons comprising PHM are distributed over at least 76 kb genomic DNA and range in size from 49-185 base pairs; four of the introns within the PHM domain are over 10 kb in length. Alternative splicing in the PHM region can result in a truncated, inactive PHM protein (rPAM-5), or a soluble, monofunctional PHM protein (rPAM-4) instead of a bifunctional protein. The eight exons comprising PAL are distributed over at least 19 kb genomic DNA. The exons encoding PAL range in size from 54-209 base pairs and have not been found to undergo alternative splicing. The PHM and PAL domains are separated by a single alternatively spliced exon surrounded by lengthy introns; inclusion of this exon results in the production of a form of PAM (rPAM-1) in which endoproteolytic cleavage at a paired basic site can separate the two catalytic domains. The exon following the PAL domain encodes the trans-membrane domain of PAM; alternative splicing at this site produces integral membrane or soluble PAM proteins. The COOH-terminal domain of PAM is comprised of a short exon subject to alternative splicing and a long exon encoding the final 68 amino acids present in all bifunctional PAM proteins along with the entire 3'-untranslated region. Analysis of hybrid cell panels indicates that the human PAM gene is situated on the long arm of chromosome 5. PMID- 1448113 TI - Ligands induce conformational changes in the carboxyl-terminus of progesterone receptors which are detected by a site-directed antipeptide monoclonal antibody. AB - We have prepared a monoclonal antibody, C-262, to a synthetic peptide that contains the carboxy-terminal 14 amino acids from progesterone receptors (PR). This sequence is 100% conserved in all species of PRs that have been cloned to date, suggesting that this antibody will recognize all mammalian and avian PR. The C-262 antibody recognizes both native and denatured forms of the receptor. However, it does not recognize PR when they are bound to the hormone agonists progesterone or R5020. Surprisingly the antibody does recognize PR when they are bound to the steroid antagonist RU486. This suggests that progestin agonists induce a conformational change in the receptor that occludes the C-262 epitope in the carboxyl-terminus, whereas unliganded receptors and receptors bound with RU486 assume distinct conformations that leaves the C-terminal tail accessible to the C-262 antibody. PMID- 1448114 TI - One of the two trout proopiomelanocortin messenger RNAs potentially encodes new peptides. AB - POMC is the precursor for a number of biologically active peptides such as ACTH, alpha-MSH, beta-MSH, and beta-endorphin. It is well known that some of these peptides, especially beta-endorphin, are involved in the regulation of reproductive functions in mammals. In order to investigate the possible role of POMC-derived peptides in the control of fish reproduction, we have cloned and sequenced two different trout POMC cDNAs called POMC A and POMC B. These cDNAs exhibited limited sequence homology (44%). The deduced amino acid sequences also showed weak similarity (43%), despite the high conservation of some peptide sequences (alpha-MSH, beta-MSH, and beta-endorphin). The POMC A coding sequence exhibited an unusual length, generating the longest endorphin ever sequenced. The long carboxy-terminal part of the beta-endorphin A contained three potential dibasic cleavage sites, allowing the occurrence of three new peptides: EQWGREEGEE, ALGE, and YHFQG. Using in situ hybridization, we found that the two POMC genes were expressed in the same pituitary cells. POMC A mRNA was the only one detectable in the hypothalamus of sexually inactive fish, whereas the two POMC genes were expressed in the hypothalamus of sexually active fish. These results indicate that two functional POMC genes are present in the rainbow trout. In POMC neurons, the expression of the POMC B gene is likely to be under the control of sexual steroids. PMID- 1448115 TI - Regulation of c-jun and jun-B by progestins in T-47D human breast cancer cells. AB - To investigate further the molecular mechanisms of progestin regulation of human breast cancer cell growth, we studied the effect of progestins on expression of the protooncogene c-jun and other members of the jun family, jun-B and jun-D, in T-47D human breast cancer cells. The progestin medroxyprogesterone acetate (MPA) increased c-jun mRNA levels in a time- and dose-dependent fashion. Maximal effects were seen after 3 h of treatment with 10-100 nM MPA. Under these conditions, the c-jun mRNA was increased 5.4-fold above the control level. Although the c-jun mRNA level was increased by cycloheximide alone, a further 2.4 fold increase was seen when the cells were treated with MPA in the presence of cycloheximide. The p39 c-jun protein was also increased 3.8-fold by this treatment. Maximum levels of p39 c-jun protein were achieved 9 h after treatment, and this level was maintained for at least 24 h. Dexamethasone and dihydrotestosterone did not increase the p39 c-jun protein level under these conditions. However, MPA treatment of T-47D cells resulted in a 55% decrease in overall AP-1 activity, as measured by transient transfection of an AP-1-regulated chloramphenicol acetyltransferase reporter gene. These effects were all reversible by cotreatment with a 10-fold higher concentration of the antiprogestin RU 486. MPA decreased jun-B mRNA levels 50% 1 h after treatment in T-47D cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448116 TI - Insulin receptor gene expression during development: developmental regulation of insulin receptor mRNA abundance in embryonic rat liver and yolk sac, developmental regulation of insulin receptor gene splicing, and comparison to abundance of insulin-like growth factor 1 receptor mRNA. AB - Insulin gene expression has been demonstrated in nonpancreatic tissues early in development, suggesting that this hormone might have actions significant for the differentiating embryo. Because such actions imply ligand-receptor binding, we quantified mRNAs encoding the two known forms of insulin receptor in rat liver and yolk sac, two endodermally derived tissues shown to express insulin genes, between gestation days (E) 13 and E21 (mid-organogenesis to parturition). Because of its presumed importance for fetal growth, we estimated the abundance of mRNA encoding insulin-like growth factor 1 (IGF 1) receptor in the same samples for comparison. The abundance of insulin receptor mRNA exceeded that for IGF 1 receptor mRNA in liver and yolk sac at all times studied. This difference was greater in liver, where insulin receptor mRNAs were three to more than 50 times more abundant than IGF 1 receptor mRNA on gestation days E13-E16, times which antedate the development of significant hepatic metabolic actions of insulin. The marked abundance of mRNAs encoding insulin receptors is consistent with the hypothesis that insulin has significant actions in specific tissues during the organogenic period. PMID- 1448117 TI - Site-directed mutagenesis of glycosylation sites in the transforming growth factor-beta 1 (TGF beta 1) and TGF beta 2 (414) precursors and of cysteine residues within mature TGF beta 1: effects on secretion and bioactivity. AB - The transforming growth factor-beta 1 (TGF beta 1) and -beta 2 (414) precursors both contain three predicted sites of N-linked glycosylation within their pro regions. These are located at amino acid residues 72, 140, and 241 for the TGF beta 2 (414) precursor and at residues 82, 136, and 176 for the TGF beta 1 precursor; both proteins contain mannose-6-phosphate (M-6-P) residues. The major sites of M-6-P addition are at Asn (82) and Asn (136), the first two sites of glycosylation, for the TGF beta 1 precursor. We now show that the major site of M 6-P addition within the TGF beta 2 (414) precursor is at Asn241, the third glycosylation site. To determine the importance of N-linked glycosylation to the secretion of TGF beta 1 and -beta 2, site-directed mutagenesis was used to change the Asn residues to Ser residues; the resulting DNAs were transfected into COS cells, and their supernatants were assayed for TGF beta activity. Substitution of Asn (241) of the TGF beta 2 (414) precursor resulted in an 82% decrease in secreted TGF beta 2 bioactivity. Mutation at Asn72 resulted in a 44% decrease, while mutation at Asn140 was without effect. Elimination of all three glycosylation sites resulted in undetectable levels of TGF beta 2. These results were compared with similar mutations made in the cDNA encoding the TGF beta 1 precursor. Mutagenesis of the two M-6-P-containing sites (Asn82 and Asn136) resulted in an 83% decrease in secreted TGF beta 1; replacement of Asn82 and Asn136 with Ser individually resulted in 85% and 42% decreases in activity, respectively. Substitution of Asn176 with Ser was without effect, while substitution of all three sites of glycosylation resulted in undetectable levels of TGF beta 1 activity, similar to the results obtained with TGF beta 2. The nine Cys residues within the mature region of TGF beta 1 were mutated to serine, and their effects on TGF beta 1 secretion were evaluated. Mutation of most Cys residues resulted in undetectable levels of TGF beta 1 protein or activity in conditioned medium. Mutation of Cys (355) led to the secretion of inactive TGF beta 1 monomers, suggesting that this residue is either directly involved in dimer formation or required for correct interchain disulfide bond formation. PMID- 1448118 TI - Characterization of the genomic corticotropin-releasing factor (CRF) gene from Xenopus laevis: two members of the CRF family exist in amphibians. AB - In mammals, the release of pituitary ACTH is stimulated by CRF. Two related peptides exist in nonmammalian vertebrates, sauvagine from frog skin and urotensin-I from the urophysis of teleost fish. Their related structures (approximately 50%) and capacity to stimulate the release of ACTH from mammalian and fish pituitaries has led to the proposal that sauvagine and urotensin-I are homologs of mammalian CRF. However, sauvagine does not appear to stimulate ACTH release in amphibians, although mammalian CRF (ovine) induces a potent response from amphibian pituitaries. This could indicate that the main function of sauvagine does not involve ACTH regulation and suggests that an additional CRF like peptide exists in Amphibia. We report here the isolation of two highly homologous CRF-like genes from the frog, Xenopus laevis. Analysis of the expression pattern of these CRF-like genes revealed mRNA in splenic tissue and in the preoptic nucleus and paraventricular organ of the brain. The amino acid sequence of the mature peptide regions (1-41) of both X. laevis genes is strikingly conserved, sharing more than 93% homology with mammalian CRFs, yet only 50% homology with sauvagine. In view of the fact that these new amphibian CRF-like genes share far greater homology with mammalian CRF than that exhibited by sauvagine, we propose that the new Xenopus CRF-like genes are the amphibian counterparts to mammalian CRF. Thus, two members of the CRF family have now been identified in the Amphibia, namely CRF and sauvagine. PMID- 1448119 TI - Promoter for the regulatory type I beta subunit of the 3',5'-cyclic adenosine monophosphate-dependent protein kinase directs transgene expression in the central nervous system. AB - Cyclic AMP-dependent protein kinase (cAPK) modulates synaptic transmission and influences memory and learning. Among the various isoforms of regulatory and catalytic subunits that comprise mammalian cAPK, only the regulatory type I beta (RI beta) subunit is unique to nervous tissue. The requirement for RI beta in neurons is presently unknown. Previous studies demonstrate that holoenzyme containing RI beta activates at lower concentrations of cAMP compared to other forms of cAPK. Thus, neurons that induce RI beta expression may become more sensitive to subsequent hormonal signals and maintain more long-term phosphorylation events. To further elucidate the function of this novel protein, we have begun to investigate its gene. Here we report the isolation of the mouse RI beta promoter as determined by S1 nuclease analysis and transgenic mouse expression. A beta-galactosidase fusion gene containing 1.5 kilobases of 5' nontranscribed RI beta DNA and 2 kilobases of intron 1 was expressed preferentially in the cortex and hippocampus of the brain and within the spinal cord. In addition to mimicking the location of endogenous RI beta expression, the transgene was activated at a similar time (embryonic day 11.5) during mouse fetal development. Isolation of the RI beta promoter will help identify the elements that direct transcription in a subset of neurons and illuminate the physiological conditions that may regulate RI beta expression. This promoter can also be used to target the expression of wild type and mutant cAPK subunit genes in order to investigate synaptic plasticity in animals. PMID- 1448120 TI - An association between collateral blood flow and myocardial viability in patients with recent myocardial infarction. AB - BACKGROUND: We hypothesized that successful reperfusion of an occluded infarct related coronary artery even late after acute myocardial infarction would result in improved regional wall motion and that such improvement might be related to the presence of collateral blood flow within the infarct bed. METHODS: We assessed regional wall motion by two-dimensional echocardiography at base line and one month after angioplasty was attempted in the occluded infarct-related artery in 43 patients who had had a myocardial infarction two days to five weeks earlier. A wall-motion score was assigned to each patient on a five-point scale (from 1 [normal function] to 5 [dyskinesia]). The percentage of the infarct bed perfused by collateral flow was assessed with myocardial contrast echocardiography. RESULTS: In the 41 patients who had abnormal wall motion at base line, improvement in function was noted in 25 (78 percent) of the 32 in whom angioplasty was successful, as compared with only 1 (11 percent) of the 9 in whom it was unsuccessful (P < 0.001). The percentage of the infarct bed supplied by collateral flow at base line was directly correlated with wall function and inversely correlated with the wall-motion score one month after successful angioplasty (r = -0.64, P < 0.001). Among the patients in whom angioplasty was successful, the 23 in whom > 50 percent of the infarct bed was supplied by collateral flow had better wall motion (P < 0.001) and greater improvement in wall motion at one month (P = 0.004) than the 9 in whom < or = 50 percent of the bed was supplied by collateral flow. The degree of improvement in function was not influenced by the length of time between the infarction and the attempted angioplasty. CONCLUSIONS: The myocardium remains viable for a prolonged period in many patients with acute infarction and an occluded infarct-related artery. Viability appears to be associated with the presence of collateral blood flow within the infarct bed. PMID- 1448121 TI - A controlled trial of trimethoprim-sulfamethoxazole or aerosolized pentamidine for secondary prophylaxis of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. AIDS Clinical Trials Group Protocol 021. AB - BACKGROUND: Pneumocystis carinii pneumonia (PCP) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome (AIDS), but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP. METHODS: We conducted a comparative, open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim-sulfamethoxazole or pentamidine. All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer. The participants were followed for a median of 17.4 months. RESULTS: In the trimethoprim-sulfamethoxazole group (n = 154) there were 14 recurrences of PCP, as compared with 36 recurrences (including 1 extrapulmonary recurrence) in the aerosolized-pentamidine group (n = 156). The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim sulfamethoxazole and 27.6 percent with pentamidine (P < 0.001). The risk of a recurrence (adjusted for initial CD4 cell count) was 3.25 times higher in the pentamidine group (P < 0.001, 95 percent confidence interval, 1.72 to 6.16). There were no significant differences between the groups in survival or in hematologic or hepatic toxicity. Crossovers from trimethoprim-sulfamethoxazole to aerosolized pentamidine were more common than the reverse (27 vs. 4 percent), partly because of the study protocols for the management of leukopenia. There were 19 serious bacterial infections in the trimethoprim-sulfamethoxazole group and 38 in the pentamidine group. The time to a first bacterial infection was significantly greater for those assigned to trimethoprim-sulfamethoxazole (P = 0.017). CONCLUSIONS: In patients with AIDS who are receiving zidovudine, trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection. PMID- 1448122 TI - The self-limited nature of chronic idiopathic diarrhea. AB - BACKGROUND: Little is known about the clinical presentation and natural history of previously healthy patients in whom chronic idiopathic diarrhea develops. METHODS: We reviewed the case records of 152 patients with chronic diarrhea who had no history of gastrointestinal surgery and who were evaluated in detail as part of a chronic-diarrhea protocol from 1985 to 1990. Patients were considered to have chronic idiopathic diarrhea if they had persistently loose stools for more than four weeks, no systemic illness, and no identifiable cause of diarrhea. RESULTS: Seventeen patients (10 men and 7 women) ranging in age from 33 to 72 years met the criteria for chronic idiopathic diarrhea. Each patient had a history of a relatively abrupt onset of symptoms, often soon after returning home from a trip, starting two to seven months before evaluation. Their diarrhea did not occur during a local outbreak of diarrhea, and other family members did not become ill. Stool frequency ranged from 5 to 25 movements per day, stool weights ranged from 417 to 1480 g per day, and fecal electrolyte and osmolality values were consistent with a diagnosis of secretory diarrhea. The results of biopsies of the small intestine and colon were normal, as were small-bowel roentgenograms. Extensive studies for infectious causes of diarrhea were negative, and no patient responded to antibiotic therapy. In every patient the diarrhea stopped without specific therapy after 7 to 31 months (mean, 15) and did not recur during a follow-up period averaging 38 months. CONCLUSIONS: Sporadic idiopathic chronic diarrhea is a recognizable syndrome that can last many months, but is self limited. PMID- 1448123 TI - Prevention and treatment of pneumocystis pneumonia. PMID- 1448124 TI - Seminars in medicine of the Beth Israel Hospital, Boston: Pancreatic and islet transplantation for diabetes--cures or curiosities? PMID- 1448125 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 51-1992. A 78-year-old woman with recurrent gastrointestinal bleeding after several intra-abdominal vascular operations. PMID- 1448126 TI - Folic acid and neural-tube defects--time for action? PMID- 1448127 TI - Suicide in the home in relation to gun ownership. PMID- 1448128 TI - Suicide in the home in relation to gun ownership. PMID- 1448129 TI - Suicide in the home in relation to gun ownership. PMID- 1448130 TI - Suicide in the home in relation to gun ownership. PMID- 1448131 TI - Prevalence of HIV-infected syringes during a syringe-exchange program. PMID- 1448132 TI - Things that go bang in the night. PMID- 1448133 TI - Adding injustice to injury. Compulsory payment for unwanted treatment. PMID- 1448134 TI - His father's Oldsmobile. PMID- 1448135 TI - Sakmann starts German-Israeli fund. PMID- 1448136 TI - Germany will ease requirements of gene technology laws in bow to researchers. PMID- 1448137 TI - EMF report draws fire. PMID- 1448138 TI - FDA wants to invite women into drug trials earlier. PMID- 1448139 TI - The brain size/IQ debate. PMID- 1448140 TI - The brain size/IQ debate. PMID- 1448141 TI - Watch that dog! PMID- 1448142 TI - Mir for the crystallographers' money. PMID- 1448143 TI - Molecular neurology comes of age. PMID- 1448144 TI - Immunology. Deconstructing the MHC. PMID- 1448145 TI - Neurobiology. Elements of visual perception. PMID- 1448146 TI - Of mice and men. PMID- 1448147 TI - Protein kinase C downregulation? PMID- 1448148 TI - Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. AB - The inhibins are alpha:beta heterodimeric growth factors that are members of the transforming growth factor-beta family. To understand the physiological roles of the inhibins in mammalian development and reproduction, a targeted deletion of the alpha-inhibin gene was generated by homologous recombination in mouse embryonic stem cells. Mice homozygous for the null allele (inhibin-deficient) initially develop normally but every mouse ultimately develops mixed or incompletely differentiated gonadal stromal tumours either unilaterally or bilaterally. Inhibin is thus a critical negative regulator of gonadal stromal cell proliferation and the first secreted protein identified to have tumour suppressor activity. PMID- 1448149 TI - Functional localization and lateralization of human olfactory cortex. AB - Anatomical and physiological investigations in monkeys indicate that olfaction is subserved by several cortical regions. But the areas implicated in the human olfactory system have not been definitively identified by functional criteria. Behavioural evidence has suggested that laterally specialized mechanisms for odour processing may exist, but the neuroanatomical substrate remains unknown. We used positron emission tomography to study the cortical representation of human olfactory processing by comparing cerebral blood flow changes evoked during olfactory stimulation with those of a control task. We report here significant cerebral blood flow increases at the junction of the inferior frontal and temporal lobes bilaterally, corresponding to the piriform cortex, and unilaterally, in the right orbitofrontal cortex. The results complement and extend previous data implicating these regions in olfactory processing, and indicate that a functional asymmetry exists in the human brain favouring the right orbitofrontal area in olfaction. PMID- 1448150 TI - Columns for visual features of objects in monkey inferotemporal cortex. AB - At early stages of the mammalian visual cortex, neurons with similar stimulus selectivities are vertically arrayed through the thickness of the cortical sheet and clustered in patches or bands across the surface. This organization, referred to as a 'column', has been found with respect to one-dimensional stimulus parameters such as orientation of stimulus contours, eye dominance of visual inputs, and direction of stimulus motion. It is unclear, however, whether information with extremely high dimensions, such as visual shape, is organized in a similar columnar fashion or in a different manner in the brain. Here we report that the anterior inferotemporal area of the monkey cortex, the final station of the visual cortical stream crucial for object recognition, consists of columns, each containing cells responsive to similar visual features of objects. PMID- 1448151 TI - Brefeldin A inhibits Golgi membrane-catalysed exchange of guanine nucleotide onto ARF protein. AB - The fungal metabolite brefeldin A is a powerful tool for investigating membrane traffic in eukaryotic cells. The effects of brefeldin A on traffic are partly explained by its ability to prevent binding of cytosolic coat proteins onto membranes. The non-clathrin coatomer complex binds reversibly to Golgi membranes in a GTP-controlled cycle. The low-molecular-mass GTP-binding protein ADP ribosylation factor (ARF), which also associates reversibly with Golgi membranes, is required for coatomer binding and probably accounts for the control by guanine nucleotide of the coatomer-membrane interaction. Brefeldin A prevents the assembly of coatomer onto the membrane by inhibiting the GTP-dependent interaction of ARF with the Golgi membrane, but the nature of this interaction has not been established. Here we demonstrate that Golgi membranes can specifically catalyse the exchange of GTP onto ARF and that brefeldin A prevents this function. PMID- 1448152 TI - Inhibition by brefeldin A of a Golgi membrane enzyme that catalyses exchange of guanine nucleotide bound to ARF. AB - A wide variety of membrane transformations important in intracellular transport are inhibited by the fungal metabolite brefeldin A (refs 1-4), implying that the target for this drug is central to the formation and maintenance of subcellular compartments. Brefeldin A added to cells causes the rapid and reversible dissociation of a Golgi-associated peripheral membrane protein (M(r) 110,000) which was found to be identical to one of the subunits of the coat of Golgi derived (non-clathrin) coated vesicles, beta-COP, implying that brefeldin A prevents transport by blocking the assembly of coats and thus the budding of enclosed vesicles. In addition to the coatomer (a cytosol-derived complex of seven polypeptide chains, one of which is beta-COP), the non-clathrin (COP) coat of Golgi-derived vesicles contains stoichiometric amounts of a small (M(r) approximately 20,000) GTP-binding protein, the ADP-ribosylation factor (ARF). Binding of ARF to Golgi membranes is necessary before coatomer/beta-COP can bind these membranes (ref. 12; and D. J. Palmer et al., manuscript submitted), so the primary effect of brefeldin A seems to be on the reaction responsible for ARF binding. Indeed, like beta-COP, ARF is dissociated from the Golgi complex by treatment with brefeldin A and brefeldin A prevents ARF from associating in vitro, but the mechanism of this action by brefeldin A has been unclear. Here we report the discovery of an enzyme in a Golgi-enriched fraction that catalyses guanine nucleotide (GDP-GTP) exchange on ARF-1 protein, and which is inhibited by brefeldin A. We suggest that activation of ARF proteins for membrane localization by compartmentalized exchange enzymes is in general the first committed step in membrane transformation pathways. PMID- 1448153 TI - Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. AB - We report here the determination and refinement to 1.9 A resolution by X-ray cryo crystallography the structure of HLA-Aw68. The averaged image from the collection of bound, endogenous peptides clearly shows the atomic structure at the first three and last two amino acids in the peptides but no connected electron density in between. This suggests that bound peptides, held at both ends, take alternative pathways and could be of different lengths by bulging out in the middle. Peptides eluted from HLA-Aw68 include peptides of 9, 10 and 11 amino acids, a direct indication of the length heterogeneity of tightly bound peptides. Peptide sequencing shows relatively conserved 'anchor' residues at position 2 and the carboxy-terminal residue. Conserved binding sites for the peptide N and C termini at the ends of the class I major histocompatibility complex binding groove are apparently dominant in producing the long half-lives of peptide binding and the peptide-dependent stabilization of the class I molecule's structure. PMID- 1448154 TI - Atomic structure of a human MHC molecule presenting an influenza virus peptide. AB - Infection by influenza virus results in the stimulation of cytotoxic T lymphocytes specific for killing virally infected cells. Specificity is provided by clonally distributed, hypervariable T-cell receptors on cytotoxic T lymphocytes which react with peptide fragments that are derived from viral proteins expressed in the cytoplasm and 'presented' on the surface of infected cells, bound to class I histocompatibility glycoproteins. Here we describe the structure of the complex between the human class I histocompatibility glycoprotein HLA-Aw68 and the influenza virus nucleoprotein peptide Np 91-99 as determined by X-ray cryocrystallography. Residues at both ends of the peptide are substantially buried in the peptide binding-site, whereas those in the middle of the peptide, P4 to P8, are predominantly exposed and could be recognized directly by T-cell receptors. The extended conformation of the bound viral peptide is remarkably similar to that of a collection of endogenous peptides with a different sequence motif bound to another human allele, HLA-B27. The structure defines in atomic detail the antigenic surface constructed of major histocompatibility complex and viral peptide atoms that is recognized by T-cell receptors. PMID- 1448156 TI - Identification by anti-idiotype antibodies of an intracellular membrane protein that recognizes a mammalian endoplasmic reticulum retention signal. PMID- 1448155 TI - The three-dimensional structure of an intact monoclonal antibody for canine lymphoma. AB - Crystal structures of Fab antibody fragments determined by X-ray diffraction characteristically feature four-domain, beta-barrel arrangements. A human antibody Fc fragment has also been found to have four beta-barrel domains. The structures of a few intact antibodies have been solved: in two myeloma proteins, the flexible hinge regions that connect the Fc to the Fab segments were deleted so the molecules were non-functional, structurally restrained, T-shaped antibodies; a third antibody, Kol, had no hinge residues missing but the Fc region was sufficiently disordered that it was not possible to relate its disposition accurately with respect to the Fab components. Here we report the structure at 3.5 A resolution of an IgG2a antitumour monoclonal antibody which contains an intact hinge region and was solved in a triclinic crystal by molecular replacement using known Fc and Fab fragments. The antibody is asymmetric, reflecting its dynamic character. There are two local, apparently independent, dyads in the molecule. One relates the heavy chains in the Fc, the other relates the constant domains of the Fabs. The variable domains are not related by this 2-fold axis because of the different Fab elbow angles of 159 degrees and 143 degrees. The Fc has assumed an asymmetric, oblique orientation with respect to loosely tethered yet almost collinear Fabs. Our study enables the two antigen-binding segments as well as the Fc portion of a functional molecule to be visualized and illustrates the flexibility of these immune response proteins. PMID- 1448157 TI - Gene therapy researcher under fire over controversial cancer trials. PMID- 1448158 TI - US genome project does it the French way, conceding that size matters after all. PMID- 1448159 TI - Biotechnology loses another battle in Germany. PMID- 1448160 TI - Dutch win a reprieve over threatened lab closing. PMID- 1448161 TI - Efficacy of leprosy vaccine. PMID- 1448162 TI - AIDS and sexual behaviour in France. ACSF investigators. AB - The results of a massive telephone survey of sexual lifestyles in France should provide a basis for prevention strategies for AIDS and sexually transmitted diseases. PMID- 1448163 TI - Sexual lifestyles and HIV risk. AB - Britain's first large, national survey of sexual attitudes and lifestyles will allow improved estimates of the magnitude of the HIV epidemic in Britain and should lead to better strategies for prevention. PMID- 1448164 TI - Evolutionary biology. What the sperm count costs. PMID- 1448165 TI - Superantigen data. PMID- 1448166 TI - Echoes of D4 receptor repeats. PMID- 1448167 TI - Production of sperm reduces nematode lifespan. AB - Sex and death are two fundamental but poorly understood aspects of life. They are often thought to be linked because reproduction requires the diversion of limited resources from somatic growth and maintenance. This diversion of resources in mated animals, often called a cost of reproduction, is usually expressed as a reduction of lifespan in mated animals, although some debate exists on the best way to measure this cost. I report here that in the soil nematode, Caenorhabditis elegans, sex significantly decreases male lifespan without reducing hermaphrodite lifespan. The reduction of mated male lifespan seems to be caused by additional sperm production and not by the physical activity of mating. This conclusion is supported by observations that a mutation reducing sperm production increased mean lifespan by about 65% in both mated males and hermaphrodites. This suggests that spermatogenesis, rather than oogenesis or the physical act of mating, is a major factor reducing lifespan in C. elegans. This contradicts the traditional biological assumption that large oocytes are much costlier to produce than small sperm. PMID- 1448168 TI - Viscous fingering of HCl through gastric mucin. AB - The HCl in the mammalian stomach is concentrated enough to digest the stomach itself, yet the gastric epithelium remains undamaged. One protective factor is gastric mucus, which forms a protective layer over the surface epithelium and acts as a diffusion barrier Bicarbonate ions secreted by the gastric epithelium are trapped in the mucus gel, establishing a gradient from pH 1-2 at the lumen to pH 6-7 at the cell surface. How does HCl, secreted at the base of gastric glands by parietal cells, traverse the mucus layer without acidifying it? Here we demonstrate that injection of HCl through solutions of pig gastric mucin produces viscous fingering patterns dependent on pH, mucin concentration and acid flow rate. Above pH 4, discrete fingers are observed, whereas below pH 4, HCl neither penetrates the mucin solution nor forms fingers. Our in vitro results suggest that HCl secreted by the gastric gland can penetrate the mucus gel layer (pH 5-7) through narrow fingers, whereas HCl in the lumen (pH 2) is prevented from diffusing back to the epithelium by the high viscosity of gastric mucus gel on the luminal side. PMID- 1448169 TI - Possible blindsight in infants lacking one cerebral hemisphere. AB - Patients with damage to the striate cortex have a subjectively blind region of the visual field, but may still be able to detect and localize targets within this region. But the relative roles in this 'blindsight' of subcortical neural systems, and of pathways to extra-striate visual areas, have been uncertain. Here we report results on two infants in whom one cerebral hemisphere, including both striate and extra-striate visual cortex, needed surgical removal in their first year. Single conspicuous targets in the half-field contralateral to the lesion could elicit fixations, implying detection and orienting by a subcortical system. In contrast, binocular optokinetic nystagmus (OKN), for which a subcortical pathway has often been thought adequate, showed a marked asymmetry. In normal neonates, fixation shifts and OKN have both been taken to reflect subcortical control; our results are consistent with subcortical control for fixation but not for OKN. PMID- 1448170 TI - Cloning and expression of a rat brain L-glutamate transporter. AB - Synaptic transmission of most vertebrate synapses is thought to be terminated by rapid transport of the neurotransmitter into presynaptic nerve terminals or neuroglia. L-Glutamate is the major excitatory transmitter in brain and its transport represents the mechanism by which it is removed from the synaptic cleft and kept below toxic levels. Here we use an antibody against a glial L-glutamate transporter from rat brain to isolate a complementary DNA clone encoding this transporter. Expression of this cDNA in transfected HeLa cells indicates that L glutamate accumulation requires external sodium and internal potassium and transport shows the expected stereospecificity. The cDNA sequence predicts a protein of 573 amino acids with 8-9 putative transmembrane alpha-helices. Database searches indicate that this protein is not homologous to any identified protein of mammalian origin, including the recently described superfamily of neurotransmitter transporters. This protein therefore seems to be a member of a new family of transport molecules. PMID- 1448171 TI - The glial cell glutamate uptake carrier countertransports pH-changing anions. AB - Uptake into glial cells helps to terminate glutamate's neurotransmitter action and to keep its extracellular concentration, [Glu]o, below neurotoxic levels. The accumulative power of the uptake carrier stems from its transport of inorganic ions such as sodium (into the cell) and potassium (out of the cell). There is controversy over whether the carrier also transports a proton (or pH-changing anion). Here we show that the carrier generates an alkalinization outside and an acidification inside glial cells, and transports anions out of the cells, suggesting that there is a carrier cycle in which two Na+ accompany each glutamate anion into the cell, while one K+ and one OH- (or HCO3-) are transported out. This stoichiometry predicts a minimum [Glu]o of 0.6 microM normally (tonically activating presynaptic autoreceptors and post-synaptic NMDA receptors), and 370 microM during brain anoxia (high enough to kill neurons). Transport of OH-/HCO3- on the uptake carrier generates significant pH changes, and may provide a mechanism for neuron-glial interaction. PMID- 1448172 TI - HLA-DR molecules from an antigen-processing mutant cell line are associated with invariant chain peptides. AB - The invariant chain, which associates with the major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum, serves two functions important in antigen processing. First, it prevents class II molecules from binding peptides in the early stages of intracellular transport. Second, it contains a cytoplasmic signal that targets the class II-invariant chain complex to an acidic endosomal compartment. Proteolytic cleavage and subsequent dissociation of the invariant chain then occurs, allowing peptides derived from endocytosed proteins to bind to released class II molecules before their expression at the cell surface. Certain human cell lines that are mutant in one or more MHC-linked genes are defective in class II-restricted antigen processing. Here we show that in transfectants of one of these cell lines, T2, this deficiency results in the association of a large proportion of class II molecules with a nested set of invariant-chain-derived peptides (class II-associated invariant chain peptides, or CLIP). HLA-DR3 molecules isolated from T2 transfectants can be efficiently loaded with antigenic peptides by exposure to a low pH in vitro, perhaps reflecting the in vivo conditions in which peptides associate with class II molecules. Addition of synthetic CLIP inhibits the loading process, indicating that CLIP may define the region of the invariant chain responsible for obstructing the class II binding site. PMID- 1448173 TI - Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes. AB - The co-ordinated function of effector and accessory cells in the immune system is assisted by adhesion molecules on the cell surface that stabilize interactions between different cell types. Leukocyte function-associated antigen 1 (LFA-1) is expressed on the surface of all white blood cells and is a receptor for intercellular adhesion molecules (ICAM) 1 and 2 (ref. 3) which are members of the immunoglobulin superfamily. The interaction of LFA-1 with ICAMs 1 and 2 provides essential accessory adhesion signals in many immune interactions, including those between T and B lymphocytes and cytotoxic T cells and their targets. In addition, both ICAMs are expressed at low levels on resting vascular endothelium; ICAM-1 is strongly upregulated by cytokine stimulation and plays a key role in the arrest of leukocytes in blood vessels at sites of inflammation and injury. Recent work has indicated that resting leukocytes express a third ligand, ICAM-3, for LFA-1 (refs 11, 12). ICAM-3 is potentially the most important ligand for LFA-1 in the initiation of the immune response because the expression of ICAM-1 on resting leukocytes is low. We report the expression cloning of a complementary DNA, pICAM 3, encoding a protein constitutively expressed on all leukocytes, which binds LFA 1. ICAM-3 is closely related to ICAM-1, consists of five immunoglobulin domains, and binds LFA-1 through its two N-terminal domains. PMID- 1448174 TI - Cloning and characterization of a new intercellular adhesion molecule ICAM-R. AB - The human intercellular adhesion molecules ICAM-1, ICAM-2 and their counter receptors, the beta 2 or leukointegrins, mediate a variety of homotypic and heterotypic leukocyte and endothelial cell-cell adhesions central to immunocompetence. It has been found that cell-cell adhesion which is dependent on expression of the leukocyte function-associated antigen LFA-1 is not always blocked completely by antibodies raised against ICAM-1 and ICAM-2. Other leukointegrin ligands therefore probably exist, such as a glycoprotein of M(r) 124K that binds LFA-1 and has been designated ICAM-3 on the basis of this function. We have molecularly cloned a new member of the ICAM family, ICAM-R, which is related to ICAM-1 and ICAM-2. The complementary DNA encoding ICAM-R is 1,781 base pairs long and the protein has five extracellular immunoglobulin family type domains. The mature cell-surface form of the ICAM-R protein has an M(r) which varies from 116 to 140K in a cell type-specific fashion. Overall identities in protein sequence with ICAM-1 and ICAM-2 are 48% and 31% respectively, with the degree of similarity varying between individual domains. The high level of expression of ICAM-R on resting leukocytes of all lineages and its lack of expression on either resting or cytokine-activated endothelial cells indicates a pattern of expression distinct from ICAM-1 and ICAM-2. In common with ICAM-1 and ICAM-2, ICAM-R is a ligand for the beta 2-integrin CD11a/LFA-1 (CD18). PMID- 1448175 TI - Imprinting and splicing join together. AB - A gene thought to be involved in RNA splicing, and which is imprinted in mice, may play an important part in Prader-Willi syndrome. PMID- 1448176 TI - Making light work with optical tweezers. AB - Microscopic objects, including biological material, can be remotely manipulated with tightly focused beams of infrared laser light. The use of optical traps, or 'optical tweezers', holds great promise for noninvasive micromanipulation and mechanical measurement in cell biology. Optical tweezers are the 'tractor beams' of today's technology. PMID- 1448177 TI - Long lasting attenuation of 8-OH-DPAT-induced corticosterone secretion after a single injection of a 5-HT1A receptor agonist. AB - The effects of 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) and some other 5-hydroxytryptamine1A (5-HT1A) receptor agonists (buspirone, ipsapirone and flesinoxan) on corticosterone secretion in rats were studied. The 5-HT1A receptors mediating the corticosterone secretion appear to be postsynaptic to the 5-HT neurons, since the response to 8-OH-DPAT was not decreased but potentiated by depletion of 5-HT with p-chlorophenylalanine pretreatment of the animals. Rapid attenuation of the response was developed after a single dose of a 5-HT1A receptor agonist. Thus, 1 mg/kg s.c. of 8-OH-DPAT attenuated the response of a challenge dose (0.1 mg/kg s.c.) of this compound within 4 h lasting between 7 and 14 d. The development of the subsensitivity was antagonized by pretreatment of the rats with the 5-HT1A receptor antagonist S-5-fluoro-8-hydroxy-2-(di-n propylamino)tetralin ((-)-UH 301). This compound also antagonized the acute effect of 8-OH-DPAT in increasing serum corticosterone. The subsensitivity development was specific for the 5-HT1A receptor-mediated corticosterone secretion, since the increase in serum corticosterone produced by stimulation of other receptor systems, e.g. alpha 2-adrenoreceptors (clonidine) or 5-HT2 receptors [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, (DOI)] was not affected. PMID- 1448178 TI - Functional expression of human 5-HT1A receptors and differential coupling to second messengers in CHO cells. AB - The signal transduction linkages of the cloned human 5-HT1A receptor as expressed stably in CHO cells were studied. A transfected clonal cell line which expresses 900 +/- 36 fmol 5-HT1A receptor/mg protein (designated CHO-5-HT1A/WT-27) responded to 5-HT and/or 8-OH-DPAT by coupling to several second messenger pathways. The 5-HT1A receptor inhibited, but did not stimulate, membrane adenylyl cyclase activity and whole cell cAMP accumulation in a dose-dependent manner (for 5-HT, IC50 = 146 +/- 27 and 55 +/- 12 nM, respectively). Activation of the receptor was associated with other signal transduction linkages: (i) a 40-50% increase in hydrolysis of inositol phosphates (for 5-HT, EC50 = 1.33 +/- 0.15 microM for 5-HT), (ii) a transient elevation of cytosolic Ca2+ levels (apparent at 1-100 microM 5-HT) which was not affected by chelation of extracellular Ca2+ by EGTA, and (iii) an augmentation of [3H]-arachidonic acid release pharmacologically with the calcium ionophore A23187 or by activation of endogenous thrombin or P2 purinergic receptors (for 5-HT, EC50 = 1.22 +/- 0.17 microM). This pathway may be an amplification mechanism for signaling in anatomic regions with high concentrations of several neuro-transmitters, hormones or autacoids, such as at neuronal junctions or near areas of platelet aggregation. All linkages were sensitive to pertussis toxin pre-treatment (IC50 approximately 0.5-0.6 ng/ml x 4.5 h for all pathways), suggesting the involvement of Gi protein(s) in these signal transduction pathways. Coupling to varied signal transduction pathways in a single cell system may be a common feature of receptors which classically inhibit adenylyl cyclase such as the 5-HT1A receptor. PMID- 1448179 TI - Characterization of the interaction of the cervane alkaloid, imperialine, at muscarinic receptors in vitro. AB - The action of the cervane alkaloid, imperialine, has been assessed at M1, M2 and M3 receptors in functional assays and at M1, M2, M3 and putative M4 sites in binding studies. In functional studies, imperialine acted as a selective surmountable antagonist at M2 receptors in guinea-pig isolated atria and uterus ( log KB = 7.7 and 7.4, respectively), in comparison to M1 receptors in canine isolated saphenous vein (-log KB = 6.9) or M3 receptors in a range of guinea-pig isolated smooth muscles including ileum, trachea, fundus, seminal vesicle or oesophagus (-log KB = 6.6-6.8). In rat aorta, the -log KB value at the M3 receptor (5.9) was slightly, but significantly, lower. In competition radioligand binding studies, imperialine was also selective toward to M2 sites in rat myocardium (-log Ki = 7.2) with respect to M1 and M3 sites (rat cerebral cortex, rat submaxillary gland; -log Ki = 6.1 and 5.7, respectively). However, it did not significantly discriminate between rat cardiac M2 sites and putative M4 sites in rabbit lung (-log Ki = 6.9). Imperialine resembles the alkaloid himbacine in terms of its pharmacological profile at muscarinic receptor subtypes in that it acts as an M2 selective antagonist with respect to M1 or M3 sites. It may also provide a second, commercially available, antagonist with which to discriminate between M1 and M4 receptors. PMID- 1448180 TI - The extraneuronal transport mechanism for noradrenaline (uptake2) avidly transports 1-methyl-4-phenylpyridinium (MPP+). AB - The corticosterone-sensitive extraneuronal transport mechanism for noradrenaline (uptake2) removes the neurotransmitter from the extracellular space. Recently, an experimental model for uptake2 has been introduced which is based on tissue culture techniques (human Caki-1 cells). The present study describes some properties of uptake2 in Caki-1 cells and introduces a new substrate, i.e., 1 methyl-4-phenylpyridinium (MPP+). Experiments on Caki-1 cells disclosed disadvantages of tritiated noradrenaline as substrate for the investigation of uptake2. The initial rate of 3H-noradrenaline transport [kin = 0.58 microliter/(mg protein.min)] was low compared with other cellular transport systems and intracellular noradrenaline was subject to rapid metabolism (kO methylation = 0.54 min-1). The neurotoxin MPP+ was found to be a good substrate of uptake2. Initial rates of specific 3H-MPP+ transport into Caki-1 cells were saturable, the Km being 24 micromol/l and the Vmax being 420 pmol/(mg protein.min). The rate constant of specific inward transport was 34 times higher [19.6 microliters/(mg protein.min)] than that of 3H-noradrenaline. The ratio specific over non-specific transport was considerably higher for 3H-MPP+ (12.6) than for 3H-noradrenaline (3.0). 3H-MPP+ transport into Caki-1 cells was inhibited by various inhibitors of uptake2. The highly significant positive correlation (p less than 0.001, r = 0.986, n = 7) between the IC50's for the inhibition of the transport of 3H-noradrenaline and 3H-MPP+, respectively, proves the hypothesis that MPP+ enters Caki-1 cells via uptake2. 3H-MPP+ is taken up via uptake2 not only by Caki-1 cells but also by the isolated perfused rat heart which is another established model of uptake2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448181 TI - Extraneuronal uptake of noradrenaline in rabbit dental pulp: evidence of identity with uptake1. AB - The extraneuronal removal and disposition of noradrenaline in rabbit dental pulp was examined in view of earlier evidence that the tissue possessed an extraneuronal uptake process resembling neuronal uptake1. Pulp, which had been depleted of sympathetic nerves by homolateral superior cervical ganglionectomy, was incubated in vitro with 3H-noradrenaline in low concentrations (0.025 or 0.18 mumol/l). When the metabolising enzymes (monoamine oxidase, catechol-O-methyl transferase) were active, 3H retention by the denervated pulp, as indicated by the 3H content after the tissue had been washed for 30 min following incubation with 3H-noradrenaline, was less than 3% of that of the innervated pulp. When the enzymes were inhibited, retention rose to approximately 30% of that of the innervated pulp. Analysis of the time course of the 3H efflux indicated that the 3H-noradrenaline in the denervated pulp had accumulated in a single compartment characterised by a t1/2 for efflux of several hours. Accumulation did not occur under Na(+)-free conditions, and was inhibited by desipramine (IC50 less than 0.03 mumol/l) and by substrates of neuronal uptake1. Mean IC50 values of the latter were very similar to those for inhibition of neuronal uptake1 and comprised (in mumol/l): (+)amphetamine (0.29), dopamine (0.31), tyramine (0.39), (-)noradrenaline (0.70), (-)adrenaline (1.50), 5-hydroxytryptamine (20) and bretylium (35). Uptake2 inhibitors were less active (O-methyl isoprenaline, IC50 = 60 mumol/l) than uptake1 inhibitors, or were without inhibitory effects at the concentrations tested (hydrocortisone, 210 mumol/l; 2-methoxy oestrone, 10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448182 TI - Stable adenine nucleotides inhibit [3H]-noradrenaline release in rabbit brain cortex slices by direct action at presynaptic adenosine A1-receptors. AB - Effects of adenosine and nucleotides on the release of previously stored [3H] noradrenaline were studied in rabbit brain cortex slices. The slices were stimulated twice, in most experiments by 6 electrical field pulses delivered at 100 Hz. Adenosine and the nucleotides AMP, ADP, ATP, AMPS, ADP beta S, ATP gamma S, beta,gamma-imido-ATP and beta,gamma-methylene-ATP all reduced the evoked overflow of tritiated compounds. For purines for which concentration-response curves were determined, the order of potency was adenosine greater than ATP approximately ATP gamma S approximately beta,gamma-imido-ATP approximately ADP greater than beta,gamma-methylene-ATP. AMP 30 mumol/l and AMPS 30 mumol/l were approximately equieffective with 30 mumol/l of adenosine and ATP gamma S, and ADP beta S 30 mumol/l was approximately equieffective with 30 mumol/l of ADP. alpha,beta-Methylene-ADP, 2-methylthio-ATP, UTP and GTP gamma S did not change the evoked overflow of tritium. alpha,beta-Methylene-ATP caused an increase; however, the increase was small and became significant only after 59 min of exposure to alpha,beta-methylene-ATP or when the slices were stimulated by 30 pulses, 10 Hz. Neither adenosine deaminase (100 U/l) nor the blocker of 5' nucleotidase, alpha,beta-methylene-ADP (10 mumol/l), attenuated the inhibition caused by ATP, ATP gamma S and beta,gamma-methylene-ATP, despite the fact that adenosine deaminase abolished the effect of adenosine. 8-Cyclopentyl-1,3 dipropylxanthine (DPCPX, 10 nmol/l) shifted the concentration-response curves of adenosine, ATP gamma S, beta,gamma-imido-ATP and beta,gamma-methylene-ATP to the right by very similar degrees. 8-(p-Sulphophenyl)-theophylline (30 and 300 mumol/l) also markedly antagonized the inhibition produced by ATP gamma S. alpha,beta-Methylene-ATP (10 and 30 mumol/l) and suramin (100 mumol/l) did not modify the effects of adenosine, ATP gamma S and beta,gamma-methylene-ATP. It is concluded that nucleotides themselves can inhibit the release of noradrenaline in the rabbit brain cortex. The nucleotides and adenosine seem to act at the same site, i.e., the A1 subtype of the P1-purinoceptor. The results support the notion that metabolically stable, phosphate chain-modified nucleotides such as ATP gamma S, beta,gamma-imido-ATP and beta,gamma-methylene-ATP can be potent P1 agonists. No evidence was found for presynaptic P2x-, P2y- or P3-purinoceptors. PMID- 1448183 TI - Lidocaine has a narrow antiarrhythmic dose range against ventricular arrhythmias induced by programmed electrical stimulation in conscious postinfarction dogs. AB - The aim of the present study was to investigate the dose-dependent antiarrhythmic efficacy of lidocaine against electrically induced tachycardias in conscious, chronically instrumented postinfarction dogs. Programmed electrical stimulation (PES) was performed in 16 dogs 8 to 21 days after a 4 h occlusion of the left anterior descending coronary artery (LAD). Infusion of saline in 8 control animals with sustained ventricular tachycardia (SVT) inducible at baseline did not affect subsequent inducibility. In the treatment group 7 of 8 animals responded with SVT and one exhibited ventricular fibrillation at baseline. After an initial bolus of 1 mg/kg lidocaine intravenously (i.v.), the drug was infused at infusion rates of 40, 80 and 120 micrograms/kg/min (i.v.). During 80 micrograms/kg/min lidocaine (mean plasma level 3.5 micrograms/ml) 7 out of 8 animals displayed an antiarrhythmic response; both the lower and the higher infusion rate were associated with a smaller antiarrhythmic efficacy (3 of 8 animals responded to 40 micrograms/kg/min and 4 of 8 to 120 micrograms/kg/min). Licocaine did not affect ventricular refractory periods, but induced an increase in intraventricular conduction time at all infusion rates, from 66.2 ms at baseline to 67.7 ms (p less than 0.05), 67.7 ms (p less than 0.05), 70.0 ms (p less than 0.01) respectively. In conclusion the present study demonstrates that lidocaine is of considerable value in the management of PES-induced ventricular arrhythmias in the postinfarction phase. However there is only a small optimal therapeutic plasma level range, where lidocaine exhibits its antiarrhythmic efficacy against this type of arrhythmia; this makes a carefully titration of the drug necessary both in the experimental and in the clinical setting. PMID- 1448184 TI - Blood pressure and gastric motor responses to bradykinin and hydrochloric acid injected into somatic or visceral tissues. AB - Both visceral and somatic nociceptive stimuli elicit reflex changes in blood pressure and gastric motor activity, but the exact type of response varies with the type of nociceptive stimulus and its site of application. Therefore, the present study compared the effects of visceral (i.p. or i.a.) and somatic (s.c.) administration of bradykinin and HCl on both mean arterial blood pressure (MAP) and intragastric pressure in anaesthetized rats. The nervous pathways mediating these responses were investigated by surgical or pharmacological inhibition of the possible reflex arcs. Bradykinin (i.a.--into the aortic arch, i.p., and s.c.), and HCl (i.p. and s.c.), elicited a fall in MAP followed by a transient increase. Intragastric pressure decreased in response to administration of these chemicals. Acute coeliac ganglionectomy reduced the gastric relaxations in response to both bradykinin and HCl, whereas vagotomy reduced only the gastric relaxations induced by HCl. Neither lesion influenced the changes in MAP after either chemical. Ablation of small diameter afferents by capsaicin or chemical sympathectomy by guanethidine reduced the changes in MAP after both chemicals, except that which occurred after i.a. injection of bradykinin. The secondary increase in MAP after i.a. and i.p. administration of algesics was increased after guanethidine. Both pretreatments reduced gastric relaxations in response to either chemical. Pretreatment of the rats with the bradykinin antagonist Hoe-140 reduced the responses to bradykinin but not to HCl. The results show that both visceral and somatic administration of painful chemicals elicit reflex falls in MAP and intragastric pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448185 TI - Hydroxysteroid sulfotransferase and a specific UDP-glucuronosyltransferase are involved in the metabolism of digitoxin in man. AB - In vitro experiments were performed with cytosolic and microsomal fractions of human liver specimens in order to investigate which enzyme forms of sulfotransferase (ST) and UDP-glucurosyltransferase (GT) are involved in the metabolism of digitoxin (dt-3) and/or its cleavage products. It was found that the cytosolic STs preferentially react with digitoxigenin (dt-0) whereas microsomal GTs conjugate digitoxigenin-monodigitoxoside (dt-1) and in traces the bisdigitoxoside (dt-2). Dt-3 and dt-0 cannot be glucuronidated. By separation of different sulfotransferases it was found that the hydroxysteroid-ST is responsible for dt-0 and 3-epidigitoxigenin (epi-dt-0) sulfation. The hydroxysteroid-ST could be purified and characterized (apparent Km and Vmax for dt-0 sulfation: approx. 17 mumol/l and 2.7 nmol/min mg protein, respectively). Of various model substrates and endogenous compounds (steroids, bilirubin) none caused a competitive inhibition of the microsomal dt-1 glucuronidation except dt 2 and dt-3. Therefore it can be supposed that a new GT form catalyses this reaction. It is characterized by an extraordinarily high affinity towards dt-1 with Km values ranging between 0.7 and 27 mumol/l. PMID- 1448187 TI - [Ultrastructure of blood-brain barrier in human brain tumors]. PMID- 1448186 TI - Reduction of postischemic leukocyte-endothelium interaction by adenosine via A2 receptor. AB - The adhesion of leukocytes to the endothelium of postcapillary venules hallmarks a key event in ischemia-reperfusion injury. Adenosine has been shown to protect from postischemic reperfusion injury, presumably through inhibition of postischemic leukocyte-endothelial interaction. This study was performed to investigate in vivo by which receptors the effect of adenosine on postischemic leukocyte-endothelium interaction is mediated. The hamster dorsal skinfold model and fluorescence microscopy were used for intravital investigation of red cell velocity, vessel diameter, and leukocyte-endothelium interaction in postcapillary venules of a thin striated skin muscle. Leukocytes were stained in vivo with acridine orange (0.5 mg kg-1 min-1 i.v.). Parameters were assessed prior to induction of 4 h ischemia to the muscle tissue and 0.5 h, 2 h, and 24 h after reperfusion. Adenosine, the adenosine A1-selective agonist 2-chloro-N6 cyclopentyladenosine (CCPA), the A2-selective agonist CGS 21,680, the non selective adenosine receptor antagonist xanthine amine congener (XAC), and the adenosine uptake blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI) were infused via jugular vein starting 15 min prior to release of ischemia until 0.5 h after reperfusion. Adenosine and CGS 21,680 significantly reduced postischemic leukocyte-endothelium interaction 0.5 h after reperfusion (p less than 0.01), while no inhibitory effect was observed with CCPA. Coadministration of XAC blocked the inhibitory effects of adenosine. Infusion of NBTI alone effectively decreased postischemic leukocyte-endothelium interaction. These findings indicate that adenosine reduces post-ischemic leukocyte-endothelium interaction via A2 receptor and suggest a protective role of endogenous adenosine during ischemia reperfusion. PMID- 1448188 TI - [Intentional hypotension therapy induced by nitroglycerin and the changes in the intracranial pressure for acute hemorrhagic intracranial lesions]. AB - It is reported that nitroglycerin (NTG) induces the elevation of intracranial pressure (ICP). Because of it, the use of NTG in patients exhibiting the increased ICP especially in the neurosurgical field is thought to be avoided. However, these reported cases dealt with normal patients. Few cases under the condition of exactly increased intracranial pressure were studied. Our 31 patients of the hemorrhagic intracranial lesion (subarachnoid hemorrhage and hypertensive intracranial hemorrhage) at the acute stage were treated by NTG infusion as an antihypertensive drug, and the ICP was measured using the epidural pressure transducer. The 31 patients were divided into three groups. Group 1 consists of the 14 patients exhibiting normal ICP (< 15mmHg). Group 2 consists of 9 patients showing elevated ICP (15mmHg < or =). Group 3 consists of 8 patients treated with glycerol before the NTG infusion. Group 1 demonstrates a statistically significant elevation of ICP corresponding with the blood pressure depression. Group 2 showed no significant elevation of it. Group 3 disclosed no remarkable elevation of it both in the elevated ICP cases and the normal ICP cases. As mentioned above, the intravenous NTG caused a remarkable increase of ICP in the normal compliance of the intracranial contents and no elevation of ICP in the poor compliance. We conclude that NTG can be used for blood pressure control at an acute stage even in hemorrhagic intracranial lesion as anti depressor. PMID- 1448189 TI - [Evaluation of cerebral blood circulation using fast magnetic resonance imaging (turbo-FLASH)]. AB - In its initial stage of development, poor time resolution was supposed to be inevitable for magnetic resonance imaging (MRI). The development of the gradient echo technique, however, has made an opening for a breakthrough to a fast MRI technique. However, conventional gradient echo technique is not fast enough to disclose the cerebral blood circulation. A new technique (turbo-FLASH), which combines gradient echo and preparation pulse, has opened the door to a true dynamic (high time resolution) MRI. The authors performed a basic study of this new fast imaging technique (Turbo-FLASH) for the evaluation of cerebral blood circulation. Using this dynamic MRI, the conventional Gd-DTPA administration (0.1mmol/kg, intravenous manual administration) has produced sufficient contrast to reveal a difference of the extent of enhancement between normal gray matter and white matter. In patients of cerebral infarction, the infarcted brain does not show any significant increase of signal intensity after the administration of contrast medium, whereas the normal brain shows a sharp increase of signal intensity after the administration of contrast medium. Indeed, many puzzling questions remain to be solved for clinical application of this new dynamic MRI. For example, the optimal quantity of contrast medium and optimal parameters for this sequence (T1 weighted or T2 weighted?) are still unknown. But, in any case, this dynamic MRI is expected to be a clinically powerful tool for the evaluation of cerebral blood flow. PMID- 1448190 TI - [Basilar artery occlusion therapy for giant aneurysm: hemodynamic analysis by hydraulic vascular model]. AB - Therapeutic occlusion of the basilar artery has been one of the alternative treatments for surgically or intravascularly inaccessible basilar bifurcation giant aneurysms. However, several problems have been reported, such as incomplete thrombosis of the aneurysms, their growth or rupture, and cerebral embolism originating from their cavities. Since hemodynamic changes after occlusion therapy are suspected to be responsible for these phenomena, they were investigated by a hydraulic vascular model. A hydraulic vascular model of the vertebrobasilar artery was constructed with silicone and glass tubes. A glass made sphere of 2.5 cm in diameter was attached to the model and was regarded as a basilar head aneurysm. A 40% glycerol solution at 25 degrees C was found to be of similar viscosity and specific gravity to those of human whole blood at 37 degrees C and was perfused in the model. A device to measure intra-aneurysmal clearance was made from a stable luminous source and a Cds photocell. Good correlation was found between the output and an intra-aneurysmal dye concentration. The dye was injected into the aneurysm and its half-life was calculated from clearance curves. It was then regarded as an index of stagnation in an aneurysmal cavity. The flow volumes were estimated as: 60ml/min to the territory of one posterior cerebral artery (PCA) and 80ml/min to the cerebellum and the brain stem. Half-life was recorded in the following conditions: 120ml/min of flow in the basilar artery (BA) into bilateral PCAs stimulating the condition before BA occlusion, and various flow values (60ml/min to 10ml/min) of P1 segment simulating the conditions after BA occlusion distal to the superior cerebellar artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448191 TI - [Ischemic complications following parent artery occlusion with detachable balloons in the treatment of large carotid aneurysms: effectiveness of 99mTc HMPAO SPECT and importance of postoperative management]. AB - Three patients with large carotid aneurysms were treated by parent artery occlusion with detachable balloons. Of these, 2 had intracavernous carotid artery aneurysms and one had a carotid-ophthalmic aneurysm. All patients underwent a formal balloon occlusion test and tolerated it well. One patient with a carotid ophthalmic aneurysm, however, developed postoperative ischemic effects. This case was that of a 55 year-old female with right visual disturbance. Her middle cerebral artery flow had been compromised during test occlusion under induced hypotension. Although initially intact after balloon occlusion, she was found to be hemiplegic 24 hours later. She subsequently developed multiple small infarcts which were shown on MRI and which corresponded exactly to the previously demonstrated region of decreased flow during testing. This ischemic complication is possibly due to hypoperfusion, but embolism from the thrombosed aneurysm can not be denied. To prevent these complications, an extracranial-intracranial artery anastomosis prior to parent artery occlusion should be considered if the preoperative 99mTc-HMPAO SPECT shows a compromised cerebral blood flow. In addition to this, postoperative anticoagulant therapy should be given even if test occlusion was well tolerated clinically. PMID- 1448192 TI - [Cyst formation following local chemotherapy of malignant brain tumor: a clinicopathological study of two cases]. AB - This paper reports clinicopathological findings concerning an enlarged bulky cyst and the tumor cavity following local administration of an anticancer agent combined with radiotherapy in two patients suffering from malignant glioma. Case 1: This 69 year-old man who had been diagnosed as having glioblastoma in the right parietal lobe had received local chemotherapy after the first operation. Simultaneously radiotherapy of 69 Gy in total dose was performed. At the second operation for the tumor, cyst formation was clinically confirmed and necrotomy as well as evacuation of the large cyst was performed after adjuvant therapy. The patient died at a time ten months after the first surgical operation. Case 2: This is the case of a 48 year-old man who was diagnosed as having gemistocytic astrocytoma in the left frontal lobe. The first surgical operation was performed and was followed by local chemotherapy as well as radiotherapy (total dose of 90 Gy in two sessions). The second surgical operation of the recurrent tumor, with necrotomy and evacuation of the large cyst were performed after adjuvant therapy. The patient expired at a time sixty-five months after the first surgical operation. Relevant to the chemotherapy, adriamycin (ADM) (0.5mg) and methotrexate (MTX) (1mg) were administered through the Ommaya's reservoir into the tumor bed at craniotomy. The usual doses of ADM and MTX amounted to 5.0mg respectively. Through conventional CT and MRI, formation of a cyst including abundant membranous debris or septi was identified in both cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448193 TI - [A case of common carotid artery stenosis due to hanging]. AB - We report a case of a 50-year-old woman with traumatic dissection of the right common carotid artery secondary to attempted suicidal hanging. Initial examination showed marks of strangulation on the neck, facial edema, and multiple conjunctival petechiae accompanied by difficulty in breathing and loss of consciousness. She gradually recovered except for her left upper limb weakness. Rehabilitation, with a diagnosis of left brachial plexus injury, was started. Two years later, she occasionally felt numbness of the left upper extremity. On her second admission, a bruit was heard on the right side of her neck. Neurological examination did not reveal any change. CT scan showed atrophic changes. Angiography demonstrated approximately 80% stenosis of the right common carotid artery which was thought to be responsible for the attacks of numbness. Right carotid endarterectomy was performed. Histological findings revealed dissection of the medial layer of the arterial wall. Complaints of numbness disappeared postoperatively, and angiography showed good patency at a follow-up examination. We conclude that the stenosis of the common carotid artery was not due to atherosclerosis but due to the dissection as a result of hanging. PMID- 1448194 TI - [A case of subfrontal schwannoma]. AB - We encountered a rare case of subfrontal schwannoma. A 55-year-old woman had received resection of a left frontal tumor because of hyposmia, at the age of 28 years. On June 10, 1989, she was admitted with the chief complaint of progressive contraction of visual field. Neurologic examination revealed anosmia, impaired vision and concentric contraction of visual field. Fundoscopy showed optic atrophy. CT examination demonstrated a calcified mass of mixed density which was occupying her nasal cavity, ethmoid sinus and anterior skull base. The lesion was enhanced with contrast medium. MRI clearly depicted the extension of the lesion and a low signal intensity area in the left frontal lobe as a postoperative scar. Angiography showed hypovascularity. The tumor was totally removed by bifrontal craniotomy on August 22, 1989. Infiltration into the brain or compression of the optic nerve was not detected. The dura on the cranial base side was damaged and lost by infiltration of the tumor, normal olfactory bulb was not able to be identified, and the cribriform plate was broken. The anterior skull base was reconstituted by covering the dural defect with cadaveric dura and the bony defect with a pericranium. HE staining showed Antoni A&B types of schwannoma. Postoperative course was uneventful. In this case, it is most likely that a remnant of the tumor resected when she was 28 years old had developed subfrontal schwannoma a long time after the operation, although the histological type at that time was unknown. It is also possible that a primary tumor in the nasal cavity or paranasal sinus may have extended into the cranium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448195 TI - [Gliosarcoma associated with von Recklinghausen's disease: a case report]. AB - A very rare case of gliosarcoma with von Recklinghausen's disease is presented. A 51-year-old man was admitted to our hospital in March 1990, because of a 2-month history of personality change and left hemiparesis. Multiple neurofibroma over his whole body with many cafe au lait spots had been present since early childhood. His mother, brothers and children also had cafe au lait spots. Neurological examination on admission revealed memory disturbance, left homonymous hemianopsia and left hemiparesis. CT scan showed a large lobular lesion in the right temporoparietal region. The medial hypodense part was sharply demarcated by a ring-like enhancement, while the lateral isodense part was homogeneously enhanced. MRI showed a sharply demarcated high intensity lesion with Gd-EDTA enhancement corresponding to the enhanced area on CT. Faint staining on angiography revealed that the blood supply to the tumor was predominantly dural. At surgery, the tumor was solid and highly vascular, and adhered tightly to the dura. The superficial part of the tumor was well demarcated from the brain tissue, but the demarcation was obscure in the deeper part. Histological findings showed two clearly defined neoplastic components: a gliomatous component that was stained for GFAP, and a sarcomatous component that had spindle-shaped nuclei and eosinophilic fibers. The patient underwent radiotherapy after surgery, but the tumor soon recurred. A second operation was performed, but the tumor had infiltrated into the scalp and he died 10 months after the first operation. This combination is very rare and has not been reported previously. PMID- 1448196 TI - [A case of cystic optic glioma involving chiasma and bilateral posterior optic pathway]. AB - A case of cystic optic glioma involving chiasma and bilateral posterior optic pathway was reported. A 26-year-old male was admitted to our hospital complaining of dysarthria and left hemiparesis. CT, MRI revealed a cystic tumor at the right basal ganglia to midbrain, a calcified one at the bilateral optic tract and left temporal to thalamic region, and a small one at the chiasma. Radiotherapy and chemotherapy were performed because anaplastic astrocytoma was suspected after stereotactic biopsy of the tumor at the right basal ganglia. The subsequent MRI showed continuity among the above three lesions to be well defined. About 2 years later, however, enlargement of the cyst, tumor invasion beyond the optic pathway and growth of the chiasmal lesion were noted, and direct surgery to the chiasmal lesion was performed. The chiasma was swollen and grayish soft tumor tissue was partly resected after aspiration of the intrachiasmal cyst. The definitive pathological diagnosis was pilocytic astrocytoma. This case was designated as a peculiar optic glioma in the following respects; the patient was an adult man suffering from dysarthria and left hemiparesis, the tumor involved not only the chiasma and the bilateral optic tract, but also the outside optic pathway and was accompanied by a large cyst. PMID- 1448197 TI - [Two cases of failure of a programmable pressure valve]. AB - Two cases of a programmable pressure valve trouble are reported. Case #1 was that of a 49-year-old male who had received a ventriculoperitoneal shunt (VPS) using a Sophy programmable pressure valve (Model S3) after the removal of the fourth ventricle ependymoma. After the VPS, the patient went through several episodes of complaining of headache due to the spontaneous movement of the rotor from the high pressure position to the medium or low pressure position. The symptom had disappeared after exchanging the valve for a new one and by setting the valve pressure at high. Examination of the removed valve revealed that the bending degree of the spring tip was insufficient, and that the opening pressures at the medium and high pressure positions were both lower than the desired range. Case #2 was that of a 62-year-old female who had received a VPS for normal pressure hydrocephalus using a Sophy programmable pressure valve (Model S3) with the valve pressure set a high. However, her symptoms did not improve, so an attempt was made to change the valve pressure from the high pressure position to the medium pressure position with a ring magnet. But the rotor could not be moved. The valve was exchanged and the valve pressure was set at medium, and the symptoms of the patient improved postoperatively. Examination of the removed valve revealed that the movement of the rotor with a ring magnet was not able to be carried out smoothly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448198 TI - [Primary intracranial melanoma: a case report]. AB - A rare case of primary intracranial melanoma is presented in a 34-year-old man with initial symptoms of persistent headache. In magnetic resonance imaging(MRI), this case had all the characteristic findings of intracranial melanoma which had been reported previously. In 123I-iodoamphetamine-single photon emission CT (123I IMP-SPECT), abnormal accumulation of 123I-IMP was recognized in early and late phase imaging, which was very specific to the lesion. This is the first report of 123I-IMP-SPECT performed on a primary intracranial melanoma. Tumor mass originated from pia mater was surgically resected, but the dissemination of tumor cells was recognized macroscopically. Pathological examination of the specimen showed very little malignant changes of melanoma cells, which was in contrast to the previous reports. Although, no standard chemotherapy of the primary intracranial melanoma has been established, DAV therapy to the dissemination of tumor cells into the subarachnoid space, and intravenous administration of interferon-beta were performed in this case. Methods of differential diagnosis and treatments of primary intracranial melanoma are reviewed and discussed. PMID- 1448199 TI - [Anterior sacral meningocele associated with tethered cord syndrome]. AB - A case of anterior sacral meningocele associated with tethered cord syndrome is reported. A 5-year-old boy was admitted for urinary and fecal incontinence which had persisted since his birth. Abdominal MRI and sacral CT showed a presacral cystic mass communicating with the spinal dural sac through a neck traversing a sacral bony defect and tethered spinal conus. Neurological examination showed that the patient had a neurogenic bladder, atrophy of the legs and anesthesia below the S3 level. Operative finding revealed a thickened filum terminale attached to the wall of the presacral meningocele. Agenesis of the nerve root below the S2 level was identified, and no neural elements entered into the sac. Untethering was performed. Postoperative course was uneventful and the patient is doing well with his neurogenic bladder gradually improving. PMID- 1448200 TI - On the significance of subterritories in the "accumbens" part of the rat ventral striatum. AB - Although many workers have appreciated the striking cytologic and neurochemical similarities of neostriatum, accumbens and olfactory tubercle, a compelling case for regarding these areas as territories in a striatal complex awaited the arguments made by Heimer and his colleagues based on their investigations of connections. A number of recent papers support this viewpoint and extend it with the characterization of three accumbal subterritories: core, shell and rostral pole. The case for separate classifications of systems traversing the accumbens has become more compelling with each study that demonstrates connectional, cytoarchitectural and neurochemical specificity conforming to the boundaries separating the core and its downstream targets from the shell and its projection fields. Furthermore, its apparent composite of core-like and shell-like characteristics distinguishes the rostral pole as yet another unique subterritory. Differences in compartmental organization distinguish the accumbens and neostriatum. The available data are consistent with the periventricular and rostrolateral enkephalin-rich zones being ventralmost parts of the neostriatal patch and matrix compartments, respectively. The accumbal cell cluster compartment, on the other hand, appears to be a separate entity, with connectional and neurochemical features that are dissimilar to both patch and matrix of neostriatum. Boundaries between the accumbens and caudate-putamen remain elusive, and the point of view that such boundaries do not exist but, rather, are represented by "transition zones" must to a large degree reflect the reality. Likewise, it is important to acknowledge that the boundaries between accumbal subterritories are not necessarily distinct or observed faithfully by all of the afferent systems. "Transition zones" appear to be particularly significant organizational features in rostral and lateral parts of the accumbens. Interestingly, histochemically distinct cell clusters tend to be numerous in boundary regions between adjacent territories and subterritories. The predominant organizational pattern appears to be one in which the core, shell and rostral pole engage different forebrain systems that possibly subserve entirely different functions mediated by distantly related mechanisms. In this regard, it is of paramount interest that the processing of information conveyed to the accumbens by diverse cortical and subcortical inputs occurs within distinct and perhaps very different dopaminergic environments in the core, shell and rostral pole (e.g., see Refs 24, 34, 90, 110). PMID- 1448201 TI - Pharmacological stimulation reveals recombinant human nerve growth factor-induced increases of in vivo hippocampal cholinergic function measured in rats with partial fimbrial transections. AB - The present study determined the effects of chronic recombinant human nerve growth factor administration [1 microgram given intracerebroventricularly q.i.d. (every other day) for three weeks] on in vivo hippocampal cholinergic function in adult rats with unilateral partial fimbrial transections. Partial fimbrial transections did not significantly alter the levels of endogenous acetylcholine or [2H4]acetylcholine in the hippocampus due to functional compensation by surviving cholinergic terminals. In animals chronically treated with nerve growth factor, the levels of endogenous choline, endogenous acetylcholine, [2H4]choline and [2H4]acetylcholine accumulated in the hippocampus on the lesioned side were not significantly different from those on the contralateral unlesioned side or from values measured in animals treated with cytochrome c, a control protein. However, changes in cholinergic parameters induced by the partial lesions or recombinant human nerve growth factor treatment became manifest when animals were challenged using pharmacological agents such as pentylenetetrazole or pilocarpine given after lithium chloride pretreatment. First, in nerve growth factor-treated animals administered the general stimulant pentylenetetrazole (10 mg/kg) 2 min prior to measuring in vivo cholinergic parameters, we observed a significant increase in the hippocampal content of [2H4]choline in both lesioned and unlesioned hippocampi. The magnitude of the increase was significantly higher on the lesioned compared to the unlesioned side. Although chronic recombinant human nerve growth factor treatment induced increases of hippocampal [2H4]choline levels, there were no concomitant increases in the level of [2H4]acetylcholine. Second, in nerve growth factor-treated animals administered lithium chloride (3 mmol/kg) 20 h prior to pilocarpine (30 mg/kg), we observed a significant enhancement of the content of endogenous acetylcholine in the hippocampus of the lesioned side. Partial fimbrial transections also reduced in vitro cholinergic parameters reflecting endogenous acetylcholine levels in hippocampal slices. The content of endogenous acetylcholine in the slices was decreased by approximately 50% and chronic nerve growth factor treatment significantly elevated this value to approximately non-lesioned control values. Similarly, reductions in spontaneous and veratridine-evoked release of endogenous acetylcholine induced by partial fimbrial transections were counteracted by recombinant human nerve growth factor treatment. These findings demonstrate that chronic recombinant human nerve growth factor treatment effectively enhances the in vivo and in vitro synthesis, storage and release of endogenous acetylcholine. The results from the in vivo studies suggest that recombinant human nerve growth factor-induced differences in functional performance of hippocampal neurons may only be manifest during behavioral and/or pharmacological stimulation. PMID- 1448202 TI - State-dependent and state-independent effects of thyrotropin-releasing hormone on medial septum neuronal activity in the brain slices of waking and hibernating ground squirrels. AB - Effects of thyrotropin-releasing hormone on spontaneous activity and responses to medial forebrain bundle stimulation were tested in the units of the medial septum diagonal band complex in slices taken from the brain of hibernating and waking ground squirrels. Administration of thyrotropin-releasing hormone (0.1 microM) into the flow of incubating medium increased the frequency of spontaneous activity of all the medial septum-diagonal band complex neurons in hibernating ground squirrels and of the majority of neurons in the waking ground squirrels. However, in the septal slices of hibernating ground squirrels this increase was significantly more pronounced. In addition, the neuropeptide slightly increased the frequency of bursts in the majority of cells with rhythmic burst activity. The excitatory influence of thyrotropin-releasing hormone on the units was preserved in conditions of synaptic blockade. In neurons from other structures (lateral septum, medial preoptic area, hippocampus) in the brain slices of both hibernating and waking ground squirrels, thyrotropin-releasing hormone did not usually affect the level of spontaneous discharges. When studying the responses of the medial septum-diagonal band complex neurons to electrical stimulation of medial forebrain bundle it was found that application of thyrotropin-releasing hormone (0.1 microM) led to the disappearance of responses in 50 and 44% of units in the hibernating and waking ground squirrels, respectively; in the rest of the neurons a disturbance of stability and probability of responses was observed. The existence of a modulatory thyrotropin-releasing hormone system which participates post-, and, probably, presynaptically in the regulation of the medial septum diagonal band complex neuronal activity is suggested. The role of thyrotropin releasing hormone and of medial septum-diagonal band complex in the neural control of hibernation/euthermic waking cycle is discussed. PMID- 1448203 TI - Fos-like expression and nuclear size in osmotically stimulated supraoptic nucleus neurons. AB - This study has analysed by immunocytochemistry the pattern of expression of Fos related proteins, as well as variations in nuclear size, after the osmotically induced activation of supraoptic nucleus neurons of the rat. In control rats most supraoptic nucleus neurons were Fos-like negative. After acute and chronic dehydration by salt-loading, the number of Fos-like positive neurons increased dramatically. The level of Fos-like immunoreactivity was higher in chronically stimulated rats, and also the neurons of the ventral region of the supraoptic nucleus were more intensely stained than those of the dorsal region. The karyometric analysis was made on electron micrographs. The mean nuclear profile area showed a significant increase in dehydrated rats with respect to the controls (73 +/- 16 microns 2 in those dehydrated for six days vs 54 +/- 13 in controls, mean +/- S.D.). However, no significant differences in this parameter were found when one-day and six-day dehydrated groups were compared. The invagination factor of the nuclear membrane, a nuclear shape indicator, decreased significantly in dehydrated rats, indicating a tendency towards spherical nuclei. It is noteworthy that the nuclear profile perimeter was constant, about 32 microns, in control and osmotically simulated rats. The higher nuclear accumulation of Fos-related antigens after six days of dehydration suggests that in chronically stimulated supraoptic nucleus neurons there is a sustained induction of cell-specific genes. Moreover, the transcription rate of the target genes containing the consensus DNA sequence TGAC/GTCA or c-AMP responsive elements recognition sites may depend upon the nuclear concentration of Fos related antigens in supraoptic nucleus neurons. Our results also suggest that the initial Fos-related antigen expression and nuclear size increase are triggered concomitantly in supraoptic nucleus neurons after a short period of osmotic stimulation. On the other hand, we propose that nuclear envelope invaginations represent a reservoir of nuclear membrane which allows dynamic changes in nuclear size and shape depending on the metabolic status of the supraoptic nucleus neurons. PMID- 1448204 TI - Lesion and electrophysiological studies on the hypothalamic afferent pathway of the milk ejection reflex in the rat. AB - The afferent pathway of the milk ejection reflex in the hypothalamus was investigated with lesion and electrophysiological methods in anesthetized lactating rats. Destruction of the central region of the mid-hypothalamus (n = 12) blocked milk ejections induced by suckling, while that of the lateral region (n = 7) had no effect. In an electrophysiological study, extracellular recordings of neurons antidromically activated by electrical stimulation of the supraoptic nucleus were obtained from the ipsilateral hypothalamus caudal to the paraventricular nucleus (n = 84). Thirty-nine neurons were examined to see whether their firing activities changed during the milk ejection reflex. A group of 13 neurons were found to show changes in their activities prior to the reflex milk ejection; the neurons displayed a brief high-frequency burst of spikes before each milk ejection in the same manner as oxytocin neurons, and none of them antidromically responded to electrical stimulation of the neurohypophysis. The bursting neurons were recorded from the dorsomedial hypothalamic nucleus (n = 6), the region just lateral to that nucleus (n = 3) and the posterior hypothalamus (n = 4). The locations were included in a region whose destruction blocked the milk ejection reflex. These results indicate that the afferent pathway of the milk ejection reflex in the rat runs through the medial portion of the hypothalamus posterior to the paraventricular nucleus and that this region contains neurons which relay the input to the oxytocin neurons projecting in the neurohypophysis. PMID- 1448205 TI - 5-Hydroxytryptamine-induced sensitization and activation of peripheral fibres in the neonatal rat are mediated via different 5-hydroxytryptamine-receptors. AB - The effects of 5-hydroxytryptamine on peripheral nociceptive fibres were studied in an in vitro preparation of the neonatal rat spinal cord with attached tail. The activation of peripheral fibres in the tail by noxious stimuli (bradykinin, capsaicin, heat) was recorded as a depolarization of a ventral root in the lumbar region of the spinal cord (L3-L5). Responses evoked by brief applications of submaximal or threshold concentrations of bradykinin or capsaicin to the tail were enhanced by 5-hydroxytryptamine and the 5-hydroxytryptamine1C/5 hydroxytryptamine2-receptor agonist alpha-methyl-5-hydroxtryptamine but not by the 5-hydroxytryptamine3-receptor agonist 2-methyl-5-hydroxytryptamine or the 5 hydroxytryptamine1-receptor agonist 5-carboxamidotryptamine. Sensitization induced by 5-hydroxytryptamine and alpha-methyl-5-hydroxytryptamine was blocked by the selective 5-hydroxytryptamine2-receptor antagonist ketanserin. Neither the 5-hydroxytryptamine3/5-hydroxytryptamine4-receptor antagonist ICS 205-930 nor the 5-hydroxytryptamine1/5-hydroxytryptamine2-receptor antagonist methiothepin blocked the 5-hydroxytryptamine-induced sensitization. The responses evoked by submaximal thermal stimuli were also enhanced following the sensitization of peripheral nociceptors with 5-hydroxytryptamine or alpha-methyl-5 hydroxytryptamine. The alpha-methyl-5-hydroxytryptamine-induced enhancement of thermal responses was reduced by ketanserin. 5-Hydroxytryptamine did not evoke a ventral root response unless peripheral fibres were sensitized with threshold concentrations of bradykinin or capsaicin. This effect was mimicked under the same conditions by 5-carboxamidotryptamine but not by alpha-methyl-5 hydroxytryptamine or 2-methyl-5-hydroxytryptamine. The excitatory effect of 5 hydroxytryptamine was blocked by methiothepin but not by ICS 205-930 or ketanserin. Neither 5-hydroxytryptamine-induced sensitization nor 5 hydroxytryptamine-evoked activation of peripheral fibres was blocked by indomethacin. These data indicate that two types of receptor are involved in the peripheral actions of 5-hydroxytryptamine in nociception. 5-Hydroxytryptamine induced sensitization involves a 5-hydroxytryptamine2-receptor, whereas 5 hydroxytryptamine-evoked excitation involves a 5-hydroxytryptamine1-like receptor. PMID- 1448206 TI - Measurements of intracellular calcium in sensory neurons of adult and old rats. AB - Cytosolic free calcium ([Ca2+]i) was measured using fluorescent digital imaging microscopy in rat dorsal root ganglion neurons isolated from animals of two age groups (adult: seven months; and old: 30 months). Neurons were enzymatically isolated and maintained in primary culture for 14 days. Cultured neurons were loaded with the fluorescent dye, Fura-2. The spatial distribution of resting [Ca2+]i was even in both adult and old rats, but the value of cytoplasmic free calcium in old neurons was significantly higher (207 +/- 37 nmol/l vs 96 +/- 23 nmol/l) in comparison with adult ones. Depolarization with 50 mmol/l K+ produced a rapid increase in [Ca2+]i in all neurons, but the values of depolarization induced increase of [Ca2+]i in old neurons were significantly lower (423 +/- 54 nmol/l) compared with cells isolated from adult rats (1011 +/- 91 nmol/l). The time of the complete restoration of [Ca2+]i to the resting level was 10-times longer in old neurons. The caffeine-induced rise of intracellular calcium was somewhat higher in neurons from old animals, and its restoration to normal level was delayed. The findings indicate a substantial alteration of the mechanisms of regulation of intracellular calcium homeostasis with neuronal ageing. PMID- 1448207 TI - Long-term reduction of vasopressin excretion induced by the central injection of an immunoconjugate (antibody to vasopressin linked to ricin A chain). AB - We have previously demonstrated that vasopressin-producing neurons are the target of monoclonal antibodies to vasopressin microinjected into the brain tissue. At the same time, this central microinjection of vasopressin-monoclonal antibody into the supraoptic nuclei produced hydro-osmotic disorders mimicking the effects of a central diabetes insipidus. In order to investigate the increase in both duration and amplitude of the biological effects seen after the injection of vasopressin-monoclonal antibody, an immunoconjugate was constructed with the vasopressin-monoclonal antibody IgG1k isotype and the cytotoxic part of the ricin molecule, the ricin A chain. The biological parameters, such as diuresis and urine osmolality which are directly regulated by vasopressin, and vasopressin excretion, were measured after the central injection of this immunotoxin/immunoconjugate. The consequences of immunotoxin injection were also studied when immunotoxin was co-injected with monensin (50 nM) which has been shown to decrease the intracellular degradation of immunotoxin, and plasma complement, which has been shown to increase the neuronal uptake of immunotoxin. Single injection of immunotoxin near the hypothalamic supraoptic nuclei significantly increased diuresis and decreased vasopressin excretion. However, these effects were only transient and disappeared 24 h later. Four successive injections of immunotoxin (one per day) with monensin induced a decrease of vasopressin excretion which was still observed after a resting period of four days after the fourth injection. The long-term reduction of vasopressin excretion was induced in rats receiving four successive injections of a mixture consisting of immunotoxin with monensin and plasma complement. In such experiments, the vasopressin content of urine remained low (55% under the baseline value), two weeks after the fourth injection of immunotoxin. At the same time, the diuresis was increased (80% above the baseline value) and urine osmolality lowered (45% under the baseline value). When non-specific IgG replaced specific antibody, vasopressin excretion, diuresis as well as urine osmolality were unchanged. The results of this study demonstrated that the use of a specific immunotoxin results in a local interference with the vasopressinergic neurons and induces a long-term reduction of vasopressin secretion. PMID- 1448208 TI - The use of a neurotoxic lectin, volkensin, to induce loss of identified motoneuron pools. AB - In this study we investigated degeneration of defined motor pools in the adult rat spinal cord and the associated changes in spinal cord in dorsal root ganglia and peripheral nerve. Degeneration of motoneurons was induced by the neurotoxic lectin, volkensin. This substance is taken up by the axons and retrogradely transported to the cell body, where it inhibits proteosynthesis and kills the neuron. Accordingly, in adult Wistar rats the peroneal or the sciatic nerve was injected with 5.0 ng volkensin, and the effect of this single injection was investigated at different intervals after the operation. Retrograde labelling by horseradish peroxidase was used to reveal the extent of cell death and glial repair was studied by immunostaining with different glial cell markers. Degenerating cells were observed in the ventral horn of the lumbar spinal cord and L4 and L5 dorsal root ganglia as early as four days after volkensin treatment and by two weeks no retrogradely labelled motoneurons could be found in the treated peroneal pool. These changes were accompanied by severe muscle weight loss. Examination of the ventral horn of the spinal cord on the treated side revealed many hypertrophic astrocytes and reactive microglial cells expressing an increased level of complement receptor type 3 immunoreactivity. In the volkensin injected peripheral nerve, distinct signs of Wallerian-like degeneration could be observed. Schwann cells identified by immunostaining to S-100 protein appeared to be preserved. Interestingly, at later stages after volkensin injection (four to eight weeks), some retrogradely labelled motoneurons were seen in the peroneal pool; their number occasionally reached 18.4% of the control pool. The dorsal root ganglia showed extensive loss of neurons and numerous abnormal neurons were found throughout the period of the study. These findings suggest that some motoneurons are able to recover from exposure to volkensin and temporary arrest of proteosynthesis. Despite this, volkensin-induced selective motoneuron death in the adult rat can be a useful experimental model for degenerative motoneuron disease. PMID- 1448209 TI - Cis-dichlorodiammineplatinum alters GABAergic structures in the immature rat cerebellum. AB - It has been reported that injection of the antitumoral drug cis dichlorodiammineplatinum at 10 days of life affects cerebellar development in rats. After a single dose of 5 micrograms/g of body weight, the formation of granule cells is decreased and the maturation of postmitotic neurons is slowed down. A substantial time after treatment, reduced cell packing density of the internal granule layer and atrophy of the molecular layer can be observed. In addition, there is degeneration of some Purkinje cells and Golgi neurons. In spite of all these alterations, the regular architecture of the cerebellar folia is retained in many places. In the present study, we used immunocytochemistry with an immune serum raised against glutamic acid decarboxylase to further characterize the cis-dichlorodiammineplatinum-induced alterations of GABAergic neurons. The aim was to examine cerebellar development and to test for factors controlling the settling of GABAergic circuits. At all post-treatment intervals, most of the Purkinje and Golgi neurons and molecular layer interneurons showed stronger anti-glutamic acid decarboxylase immunoreactivity than in controls; this may have been due to altered fixation because of cis-dichlorodiammineplatinum induced damages to the blood vessels; but could also reflect cellular retention of the enzyme, maybe due to cis-dichlorodiammineplatinum-induced damage of the microtubular apparatus. After seven days, large roundish immunoreactive varicosities were present in the molecular layer adjacent to the Purkinje cell dendritic poles. These varicosities, which were not observed in control animals, may be terminals of Purkinje cell axon recurrent collaterals contributing to the supraganglionic plexus, whose abnormal development would compensate for the reduced inhibitory inputs from inhibitory interneurons and/or Purkinje cells, which degenerated at early post-treatment intervals. At later post-treatment intervals (15 and 21 days), there were also alterations in the pericellular basket at the Purkinje cell axon hillock, which was poorly developed in or absent from the majority of cells. The finding was confirmed by morphological observation of basket cells in Golgi-Cox preparation and immunocytochemistry with an antibody raised against 200,000 mol. wt phosphorylated neurofilaments. It is concluded that early changes in anti-glutamic acid decarboxylase immunoreactivity of neurons may be due to a direct interference of the drug with the cellular metabolic pathways. The late anomalies in the anti-glutamic acid decarboxylase immunoreactivity appear to be secondary to changes in the tissue cytoarchitecture rather than being primary cis-dichlorodiammineplatinum-induced lesions of the cells. PMID- 1448210 TI - Communicating in a decentralized system... PMID- 1448211 TI - Refusal of treatment. PMID- 1448212 TI - Medigap insurance policies standardized. PMID- 1448214 TI - Voice mail leave you tongue-tied? PMID- 1448215 TI - Six sets of clinical practice guidelines for 1992. PMID- 1448213 TI - Parental rights: who pays the price? PMID- 1448216 TI - Eight premises for a reformed American healthcare system. American Organization of Nurse Executives. PMID- 1448218 TI - Protecting patient safety in new product evaluation. PMID- 1448217 TI - Navigating the maze of capital equipment acquisition. PMID- 1448219 TI - Nurses and market research. PMID- 1448220 TI - Pharmaceutical services in the 1990s. PMID- 1448221 TI - Collaboration in evaluating patient management protocols. PMID- 1448222 TI - Voyage to shared governance. PMID- 1448223 TI - Substance abuse among nurses at teaching hospitals. PMID- 1448224 TI - Health reform: everybody plays and everybody pays. PMID- 1448225 TI - A comprehensive diabetes education program. PMID- 1448226 TI - Pressure areas: standard protocols improve care. PMID- 1448227 TI - Innovations in staffing: the resource nurse. PMID- 1448228 TI - Decentralization in cardiac services. PMID- 1448229 TI - Nine rules of thumb to make communications work. PMID- 1448230 TI - The clinical ladder in a rural hospital. PMID- 1448232 TI - 13 steps to collegiality. PMID- 1448231 TI - Interim nurse manager: a survival guide. PMID- 1448233 TI - Using LPN experience: modular nursing. PMID- 1448234 TI - Career scope--North East. PMID- 1448235 TI - The value of imaging in the diagnosis of thyroid cancer. PMID- 1448236 TI - Morphologic (CT) and functional (rCBF-SPECT) correlates in Alzheimer's disease. AB - Thirty-five patients with a clinical diagnosis of probable Alzheimer's disease underwent computed tomography (CT) and regional cerebral blood flow (rCBF) studies using single photon emission computed tomography (SPECT). Two sets of images in each subject were scored for the extent of structure and function changes. Thirty-four of 35 patients had various degrees of atrophy on CT, 33 of whom also had perfusion deficits of varying severity. One patient with normal CT had perfusion deficits, and another patient with a normal perfusion pattern had changes on CT. Regional perfusion deficits on SPECT were seen with and without associated changes on CT. Correlations were studied between CT and SPECT scores using Spearman's rank correlation coefficients. While regional scores on CT and SPECT did not significantly correlate, the total and left hemisphere scores on two sets of images showed fair correlations (r = 0.425 and r = 0.535, respectively, P less than 0.01). The correlations between cognitive performance in patients as assessed on Mini-Mental State Examination (MMSE) and CAM-COG and perfusion scores were highly significant while CT scores showed lower correlations. These findings suggest that the relationship between structural and functional changes in Alzheimer's disease is not straightforward and that the extent of changes in function as assessed by regional cerebral blood flow studies is a reliable measure of deficits in cognitive function. PMID- 1448237 TI - Left ventricular ejection fraction and volumes calculated from dual gated SPECT myocardial imaging with 99Tcm-MIBI. AB - Dual gated (DG) cardiac single photon emission computed tomographic (SPECT) studies at end-diastole (ED) and end-systole (ES) were acquired in 27 ischaemic heart disease (IHD) patients after intravenous injection of 555-740 MBq 99Tcm MIBI. Acquisition parameters were: 180 degrees from LPO to RAO, 32 projections, 64 x 64 matrix, 75 cardiac beats per projection, 80 ms at ED and 80 ms at ES for each cardiac cycle. A computer program was developed to calculate the ED and ES left ventricular (LV) volumes and LV ejection fraction (EF). The computational approach is interactive, semi-automatic and iterative with built-in visual quality control. Short axis slices are used with corresponding ED and ES slices processed as pairs from apex to base. Left ventricular cavity pixels are identified and summed on a slice-by-slice basis. Myocardial pixels are similarly identified. The computed LVEF and ED and ES volumes have been correlated with those from contrast ventriculography (CV). The mean calculated EF for 27 patients was 53.6 +/- 10.7% from DG SPECT versus 55.3 +/- 12.1% from CV (NS). The EF linear correlation coefficient was r = 0.97. PMID- 1448238 TI - Patterns of regional cerebral blood flow in Alzheimer's disease. AB - Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease. PMID- 1448239 TI - Rapid quality control of 99Tcm-sestamibi. AB - The thin layer chromatographic (TLC) method for determining the radiochemical purity of 99Tcm-sestamibi suggested by the manufacturer of the kit is slow and inconvenient. In this study a more rapid reversed phase chromatography (Sep-Pak) technique is compared with the TLC method for measurement of the radiochemical purity of 99Tcm-sestamibi. The levels of free 99Tcm-pertechnetate in 99Tcm sestamibi were accurately determined using the Sep-Pak technique. However, due to binding of variable amounts of reduced-hydrolysed unbound 99Tcm to the chromatography cartridge, the Sep-Pak method overestimated the radiochemical purity of the radiopharmaceutical by approximately 3%. In practice, this overestimation is not important and the Sep-Pak technique can be used as a rapid method of determining radiochemical purity of 99Tcm-sestamibi. PMID- 1448240 TI - 67Ga-9N3 uptake by xenografts of human melanotic melanoma in mice. AB - Tumour uptake of the inert, neutral complex 67Ga-9N3 and the tumour:blood concentration ratio (1,4,7,triazacyclononane-1,4,7, triacetic acid) were measured in mice bearing xenografts of the human melanotic melanoma HX118. Between 1 and 4 h after the injection the tumour:blood ratio increased from 3.5 to 21 and the concentration of 67Ga-9N3 in the tumour decreased from 0.43 to 0.13% g-1. During the first 24 h the concentration of 67Ga-9N3 in the tumour exceeded that in all other tissues except the liver and kidneys. The tumour:blood ratio and tissue distribution of 67Ga-9N3 at 4 h were compared with those of four other complexes. The results indicated that of the five complexes 67Ga-9N3 would be the most suitable for tumour imaging at early times after administration. Imaging would not be restricted to gamma emitting 67Ga as there is also the possibility of using the 9N3 ligand to bind 111In for single photon emission computed tomography (SPECT), 68Ga for positron emission tomography (PET) or even stable Ga for direct in vivo nuclear magnetic resonance (NMR) detection. PMID- 1448241 TI - A file format for the exchange of nuclear medicine image data: a specification of Interfile version 3.3. AB - Working Group 1 of the European project COST-B2 on quality assurance of nuclear medicine software has been concerned with the development of an appropriate mechanism for the transfer of nuclear medicine image data files between computer systems from different vendors. To this end a protocol based upon Report No. 10 of the American Association of Physicists in Medicine (AAPM) [1] was adopted. A previous publication [2] gave a specification (V3.2) for an intermediate file format with a list of key-value pairs for the header data associated with nuclear medicine image data files. This paper presents a revised specification for the intermediate file format and associated keys, now called V3.3, which has evolved from the experience in using the earlier version. It is hoped that the modifications proposed will improve the definition and usability of the file format as given in the earlier version. PMID- 1448242 TI - Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy. AB - OBJECTIVE: To determine the contributions of uterine artery diameter and mean flow velocity to the increase in volumetric flow during human pregnancy. METHODS: Volunteers (18 pregnant and six not pregnant) were studied using both a commercially available Doppler instrument with imaging ultrasound and an improved Doppler instrument with software that can determine instantaneous true mean blood flow velocity. Diameter and mean flow velocity measurements were combined to yield volumetric flows in the common iliac, external iliac, and uterine arteries during and after pregnancy. RESULTS: Compared with the nonpregnant state, uterine artery diameter doubled by week 21 (from 1.4 +/- 0.1 to 2.8 +/- 0.2 mm; P < .05), did not change between weeks 21 and 30 (2.9 +/- 0.1 mm), and increased between weeks 30 and 36 (to 3.4 +/- 0.2 mm). Uterine artery mean flow velocity rose progressively from nonpregnant values to attain at week 36 a velocity nearly eight times faster (8.4 +/- 2.2 versus 61.4 +/- 3.0 cm/second; P < .05). Unilateral uterine artery blood flow at week 36 was 312 +/- 22 mL/minute. CONCLUSIONS: Compared with nonpregnant values, common iliac artery flow increased and external iliac artery flow decreased during pregnancy, suggesting that redistribution of pelvic flow to favor the uterus contributed to the pregnancy associated rise in uterus artery flow. Early in pregnancy, the increase in uterine artery blood flow was due in equal parts to changes in uterine artery diameter and mean flow velocity, whereas late in pregnancy, the rise was due mainly to faster mean flow velocity. PMID- 1448244 TI - Does closure of Camper fascia reduce the incidence of post-cesarean superficial wound disruption? AB - OBJECTIVE: To determine whether closure of Camper fascia prevents the development of superficial wound disruption after cesarean delivery. METHODS: During a 1-year period, 438 women undergoing cesarean delivery were randomized into groups with and without approximation of Camper fascia with absorbable suture during closure of the abdominal incision. All women received routine postoperative care following our departmental guidelines. We reviewed charts after the puerperium to identify women with postoperative superficial wound disruption and to obtain demographic and delivery information for analysis. RESULTS: We found a significantly higher incidence of wound disruption in the group without the suture than in those in whom the tissue was approximated (P = .03). Four or more vaginal examinations and higher body mass index were also associated with a higher incidence of wound disruption (P = .05 and P = .04, respectively). Logistic regression correction for covariables that might influence the results of our main analysis revealed no effect of maternal age, parity, indications for cesarean delivery, duration of labor, duration of ruptured membranes, duration of surgery, use of internal monitoring, type of incision, use of antibiotic prophylaxis, surgeon's level of training, or maternal diabetes mellitus and/or hypertension. CONCLUSION: Approximation of Camper fascia with absorbable suture at closure of the abdominal incision during cesarean delivery appears to protect against postoperative superficial wound disruption and is therefore recommended. PMID- 1448243 TI - Maternal-fetal HLA-DR relationships and pregnancy-induced hypertension. AB - OBJECTIVE: Some studies have found an increased prevalence of pregnancy-induced hypertension among women sharing HLA antigens with their spouses or fetuses, thus supporting the hypothesis that maternal sensitization to fetal HLA alloantigens reduces the risk for pregnancy-induced hypertension. However, not all studies have confirmed these findings. No investigators have examined the four different types of maternal-fetal HLA relationships in their studies of pregnancy-induced hypertension. Our goal was to examine such associations to test further the HLA allosensitization hypothesis. METHODS: We conducted a cohort study of pregnancy induced hypertension among 683 nulliparous women. Women and their neonates were typed for HLA-A, -B, -DR, and -DQ antigens using serologic techniques to establish maternal-fetal relationships. RESULTS: We found an increased prevalence of pregnancy-induced hypertension when the fetus, but not the mother, was potentially exposed to HLA-DR alloantigens (maternal allogenicity) compared with the other three conditions combined (P < .003). Controlling for confounding factors, the increased prevalence of pregnancy-induced hypertension persisted in situations of maternal HLA-DR allogenicity (P < .007). CONCLUSIONS: Based upon our observations and other immunologic studies of pregnancy-induced hypertensive and uncomplicated pregnancies, we conclude that a maternal humoral response against fetal anti-HLA-DR immunoglobulin (IgG) antibody may influence the development of pregnancy-induced hypertension. This could occur when an immunocompetent fetus is exposed to maternal HLA-DR alloantigens, maternal exposure to fetal HLA-DR alloantigens alloantigens, maternal exposure to fetal HLA-DR alloantigens is not possible, and fetal IgG antibody bears paternally inherited markers allogeneic to the mother. PMID- 1448245 TI - Effect of time and storage temperature on amniotic fluid glucose concentration. AB - OBJECTIVE: To evaluate the effects of time and storage temperature on amniotic fluid (AF) glucose concentration. METHODS: Amniocentesis was performed on 47 patients with preterm labor or preterm rupture of membranes at or before 34 weeks' estimated gestation and the AF was cultured for aerobic, anaerobic, Mycoplasma, and Ureaplasma organisms. Twenty-one samples were stored at 37C, 13 were kept at room temperature (22C), and 13 were frozen (-20C). Glucose concentration was measured at 0 and 12 hours on all AF samples and at 2, 4, and 6 hours on the unfrozen samples. RESULTS: No significant change in AF glucose concentration occurred over time at any storage temperature in the 35 samples with negative cultures. In 12 AF samples with positive cultures, a significant decrease from baseline was noted at 2 and 4 hours in those kept at 37C and 22C (P = .016). Glucose concentration was unchanged in frozen samples regardless of the culture results. The initial AF glucose concentration was significantly lower in samples with positive than in those with negative cultures (P < .0001). CONCLUSION: Amniotic fluid glucose concentration does not change over 12 hours in the absence of intra-amniotic infection. PMID- 1448246 TI - Loop electrosurgical excision procedure of the transformation zone and colposcopically directed punch biopsy in the diagnosis of cervical lesions. AB - OBJECTIVE: To estimate the disagreement between the histologic reports at colposcopically directed punch biopsy of the cervix and subsequent loop excision of the transformation zone, and to assess the indications for loop excision in current practice. METHODS: The histologic diagnoses from loop electrosurgical excision procedures and concurrent colposcopically directed punch biopsies were compared in 337 consecutive women undergoing loop excision in a 5-year period. RESULTS: Disagreement between punch biopsy and loop excision was recorded in 190 cases (56.4%). The undercall and overcall rates for punch biopsy were 14 and 42.4%, respectively. Undercall at punch biopsy occurred in 24 of 46 cases of cervical intraepithelial neoplasia (CIN) III and in one microinvasive cancer diagnosed at loop excision, and disagreement was within one grade of CIN in 16 cases. CONCLUSIONS: Loop electrosurgical excision allows further and more accurate histologic examination of the transformation zone and should be the standard assessment procedure in all cases of CIN II detected at punch biopsy and whenever cytology or colposcopy suggests the risk of punch biopsy undercall. Immediate treatment by local destruction should not be performed, to avoid underestimation of the severity of the lesion. PMID- 1448247 TI - Chorionic villus sampling: experience with 3016 cases performed by a single operator. AB - OBJECTIVE: To describe our experience with 3016 first-trimester chorionic villus sampling (CVS) procedures, all performed by a single operator, to assess the influence of operator experience on the safety and efficacy of CVS. METHODS: Transcervical or transabdominal CVS procedures were performed on 3016 patients between the gestational ages of 9-12 weeks. The sampling success rate, procedure complications, cytogenetic results, and pregnancy outcomes were tabulated and analyzed. RESULTS: Samples adequate for diagnosis were obtained in 99.7% of the cases. The mean (+/- standard deviation) number of insertions per procedure was 1.1 +/- 0.4. The percentage of procedures in which the sample was obtained with a single insertion increased from 51% in the first 100 cases to 96% in the last 2516 cases. There were 56 (1.94%) first- and second-trimester pregnancy losses among 2892 pregnancies intended to continue. This loss rate compares with published baseline risk figures for miscarriage of approximately 2-3%. No difference in pregnancy loss rate followed one or two catheter or needle insertions, but the need for three insertions was associated with a significantly increased loss rate (6.7 versus 1.9%; chi 2 = 4.35, P < .05). CONCLUSION: Operator experience plays a significant role in the safety and efficacy of CVS. PMID- 1448248 TI - Prediction of the small for gestational age infant: which ultrasonic measurement is best? AB - OBJECTIVE: To determine the most appropriate ultrasonic measurement for the prediction of a small for gestational age (SGA) infant. DATA SOURCES: A literature search of all English language journals over the last 15 years was undertaken. One hundred seventeen articles on the use of morphometric and Doppler ultrasonic measurements in the diagnosis of SGA were reviewed. METHODS OF STUDY SELECTION: Studies were included if antenatal and postnatal criteria for diagnosis were clearly defined and data for SGA and normal fetuses were reported, allowing the construction of a 2 x 2 table. DATA EXTRACTION AND SYNTHESIS: Studies with the same criteria were grouped according to whether the population was high or low risk. The sensitivity, odds ratio (OR), and false-positive rate were calculated for each study; summary statistics were then calculated for each ultrasonic measurement provided the individual sensitivities, ORs, and false positive rates were not significantly different (P > .01). CONCLUSIONS: In high risk subjects, abdominal circumference below the tenth percentile had the highest common sensitivity, and estimated fetal weight below the tenth percentile had the highest common OR. In studies in which morphometric and Doppler ultrasonic measurements were compared in the same subjects, the Doppler ORs tended to be lower than the ORs for morphometric measurements. In low-risk subjects, much lower ORs were found for all ultrasonic measurements. The heterogeneous nature of the studies reviewed may have contributed to the different results within each group. PMID- 1448249 TI - Assessment of rapid identification tests for genital carriage of group B streptococci. AB - OBJECTIVE: The purpose of this study was to assess the relative value of reported methods for rapid identification of group B streptococcal colonization of the female genital tract. DATA SOURCES: Trials of group B streptococcal identification techniques published in peer-reviewed journals were located using a computerized literature search and cited references from relevant articles or text chapters. METHODS OF STUDY SELECTION: Reports were included in the analysis if the methodology fulfilled the following criteria: 1) A reference culture method was used for comparison; 2) performance characteristics were presented or could be calculated; 3) the method could be performed in a standard laboratory on a 24-hour-a-day basis; and 4) results could be routinely available within 12 hours. DATA EXTRACTION AND SYNTHESIS: Performance characteristics such as sensitivity, specificity, and predictive values for the various methods were evaluated and compared. Factors such as colonization rates and methods for identifying carriers were included in the overall assessment of test performance. CONCLUSIONS: The overall sensitivity of current methods for the rapid detection of group B streptococcal colonization is low. However, some rapid antigen detection tests are highly sensitive in identifying heavily colonized patients, and therefore may be useful for selecting high-risk patients for intrapartum antibiotic prophylaxis. PMID- 1448250 TI - Rapid fetal lung maturity testing: commercial versus NBD-phosphatidylcholine assay. AB - We compared the TDx Fetal Lung Maturity test and the fluorescence polarization method using 1-palmitoyl-2(6-[(7-nitro-2,1,3-benzoxadiazol-4- yl)amino]caproyl)phosphatidylcholine (NBD-phosphatidylcholine). Using 76 paired human amniotic fluid samples, the fluorescence polarization values of the two methods were found to have a strong nonlinear correlation (r2 = 0.946). Both assays can be completed in less than 1 hour, have excellent precision (between day variation less than 2%), and indicate the amount of surfactant phospholipid relative to albumin. The FLM assay is calibrated with surfactant/albumin standards; therefore, the reported results (in mg/g) correlate inversely with polarization of NBD-phosphatidylcholine. Strong correlations were seen for both assays with the lecithin-sphingomyelin ratio and phosphatidylglycerol. The correlations indicate that the recommended reference range for FLM will have more false predictions of immaturity than the NBD-phosphatidylcholine assay. PMID- 1448251 TI - A technique for laparoscopic pomeroy tubal ligation with endoloop sutures. AB - A laparoscopic technique of Pomeroy tubal ligation using endoloop sutures was compared with the conventional technique of laparoscopic tubal ligation with Silastic rings. Fifty-three patients selected from a population undergoing tubal ligation were randomized to either the Pomeroy (N = 28) or ring (N = 25) group. Mean (+/- standard deviation) operative time for the Pomeroy group was 27.39 +/- 5.95 minutes, with a range of 18-40; for the ring group, the time was 23.11 +/- 11.53 minutes, with a range of 12-58. These times were not statistically different. Operative complication were encountered only in the ring group and included two lacerations of the mesosalpinx. There were no technical or method failures over a follow-up interval of 12-18 months. Specimens confirmed tubal histology in all cases in the Pomeroy group. Laparoscopic Pomeroy tubal ligation using endoloop sutures was easily performed, comparable to laparoscopic application of Silastic rings, and provided a surgical specimen to confirm tubal histology. This aspect may represent a medicolegal advantage of documentation not available with other laparoscopic techniques of tubal ligation. PMID- 1448252 TI - Coping with extraperitoneal insufflation during laparoscopy: a new technique. PMID- 1448253 TI - Antenatal treatment of alloimmune thrombocytopenia. PMID- 1448254 TI - Hysteroscopic endometrial ablation using the rollerball electrode. PMID- 1448255 TI - Randomized comparison of laparoscopy-assisted vaginal hysterectomy with standard vaginal hysterectomy in an outpatient setting. AB - OBJECTIVE: To compare outpatient laparoscopy-assisted vaginal hysterectomy with standard outpatient vaginal hysterectomy. METHODS: Fifty-six women scheduled for vaginal hysterectomy were randomly assigned to undergo either a laparoscopy assisted vaginal hysterectomy with endoscopic staples (N = 29) or a standard vaginal hysterectomy (N = 27). There were no differences between the study groups with regard to age, gravidity, parity, preoperative indications, and previous operations. RESULTS: Twenty-eight of 29 laparoscopy-assisted vaginal hysterectomies and all 27 vaginal hysterectomies were completed without incident. When indicated, unilateral or bilateral oophorectomies were completed. The mean operating time was significantly longer for laparoscopy-assisted vaginal hysterectomy (120.1 versus 64.7 minutes). Fifty-three of the 55 patients completing surgery were discharged home by 12 hours from the time of admission. Complications with laparoscopic hysterectomy were related to the technical aspects of laparoscopy. The incidence of febrile morbidity was similar in the groups. Although patients having laparoscopy-assisted hysterectomy required statistically significantly more pain medication and had lower postoperative hematocrit measurements, this did not make a clinical difference in the postoperative courses. The mean hospital charge for laparoscopy-assisted vaginal hysterectomy was $7905 and for vaginal hysterectomy $4891. CONCLUSION: Other than cost, laparoscopy-assisted vaginal hysterectomy and standard vaginal hysterectomy appear comparable in patients who could otherwise undergo a vaginal hysterectomy. PMID- 1448256 TI - Appropriateness of hysterectomies performed for multiple preoperative indications. AB - OBJECTIVE: To correlate the listing of multiple preoperative indications for hysterectomy with the risk of non-confirmation of the preoperative diagnosis. METHODS: Records of 171 women undergoing consecutive hysterectomies for all indications at a large teaching hospital were reviewed for preoperative indication(s), compliance with published preoperative validation criteria for cases in which tissue pathology was not expected, and histologic verification of the preoperative diagnosis for cases in which tissue pathology was expected. Rates of confirmation (histologic verification plus successful compliance with validation criteria) of the preoperative diagnosis were compared between subgroups of cases in which single indications were listed (N = 124) or multiple indications were listed (N = 47) preoperatively. RESULTS: The rate of confirmation of single indications (115 of 124 cases, 93%) was significantly higher than the rate of confirmation of even one indication in cases in which multiple indications were listed (28 of 47 cases, 60%, P < .0001; relative risk for non-confirmation of multiple indications = 1.55). Multiple indications were more likely to be listed when tissue pathology was not expected, representing 49% of validatable indications as compared with only 18% of histologically verifiable indications (P < .0001). Overall, the rate of compliance with validation criteria (70%) was significantly lower than the rate of histologic verification (90%) (P < .01). CONCLUSION: These data suggest that listing of multiple preoperative indications for hysterectomy is associated with both decreased appropriateness, as reflected in decreased compliance with generally accepted preoperative validation criteria, and decreased diagnostic accuracy, as reflected in lower rates of histologic verification. PMID- 1448257 TI - The effect of bilateral pudendal blockade on the static urethral closure function in healthy females. AB - OBJECTIVE: To evaluate the effect of bilateral pudendal blockade on the urethral closure function in the resting state in healthy women. METHODS: Synchronous measurements of pressure and cross-sectional area were recorded at the bladder neck, in the high-pressure zone, and in the distal urethra before and after the pudendal blockade in ten women. RESULTS: The blockade reduced the resting pressure significantly (P < .01) all along the urethra. The viscoelastic indices of elastance (reciprocal of compliance) and hysteresis (difference in pressure at a given degree of urethral dilation when this is increased and decreased stepwise) were significantly (P < .05) reduced. CONCLUSIONS: The striated muscles innervated by the pudendal nerve are of paramount importance for the closure function in the resting state all along the urethra. Urethral elastance and hysteresis seem to depend on activity in the surrounding striated muscle fibers. PMID- 1448258 TI - Transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease. AB - OBJECTIVE: To evaluate transvaginal sonographic findings in ambulatory patients with suspected pelvic inflammatory disease (PID). METHODS: We studied 51 outpatients with a mean age of 26.8 years (range 16-52) who had a history of low abdominal pain, negative pregnancy test, and no gynecologic procedures performed during the last month. Endometrial biopsy was used for the histopathologic diagnosis. The presence of plasma cell endometritis was used as the criterion standard for the diagnosis of PID. Sonography was performed before biopsy in a blinded fashion without knowledge of the clinical findings and laboratory results except for the pregnancy test. Repeat pelvic and ultrasound examinations were performed 4 weeks after antimicrobial therapy. RESULTS: Endometrial biopsy revealed plasma cell endometritis in 13 cases (25%). Thickened fluid-filled tubes were seen in 11 of 13 patients (85%) with plasma cell endometritis and in none of those without. Other sonographic findings associated with plasma cell endometritis were polycystic-like ovaries and free pelvic fluid. A sonogram suggestive of PID, ie, thickened fluid-filled tube with or without free pelvic fluid, had a sensitivity of 85% and a specificity of 100% for the diagnosis of plasma cell endometritis. None of the patients with a normal sonogram or simple cyst had plasma cell endometritis. Repeat examination after 4 weeks showed that the sonographic findings had resolved in 60% of the patients who had had histologic evidence of infection. CONCLUSION: Transvaginal sonography can facilitate the outpatient management of patients with suspected PID. PMID- 1448259 TI - Transvaginal ultrasound, color flow, and Doppler waveform of the postmenopausal adnexal mass. AB - One thousand postmenopausal women were examined prospectively with transvaginal ultrasound. Seven hundred forty-three (74%) were asymptomatic and presented for screening. Data were analyzed to determine the accuracy of this new modality. Eighty-three women had surgery, and 29 malignant neoplasms were found. Color flow was identified in 27 of 29 malignant tumors and 35% of benign masses. A cutoff value of 0.41 for the Doppler resistance index in the feeder vessels had the best discriminatory value; sensitivity and specificity were 96 and 95%, respectively, for separating benign from malignant neoplasms. Positive and negative predictive values were 96 and 95%, respectively. Morphology alone had poor sensitivity, but when combined with Doppler indices, the sensitivity improved to 90% and the positive and negative predictive values were 90 and 96%, respectively. The results of this study suggest that in the postmenopausal ovary, transvaginal B mode imaging, color flow, and Doppler indices satisfy criteria as tests that may be sensitive and specific enough for application in a screening program. PMID- 1448260 TI - A critical evaluation of transvaginal Doppler studies, transvaginal sonography, magnetic resonance imaging, and CA 125 in detecting ovarian cancer. AB - OBJECTIVE: To evaluate whether transvaginal Doppler ultrasound is more valid than transvaginal sonography, magnetic resonance imaging (MRI), and CA 125 in differentiating malignant from benign ovarian tumors. METHODS: Sixty-three patients with ovarian tumors (36 benign and 27 malignant) were studied with transvaginal Doppler ultrasound before surgery. Blood flow velocity waveforms arising from intratumoral and/or tumor surface arteries were assessed by calculating the resistance index. Transvaginal B-mode sonography and MRI imaging examinations were also conducted. Serum CA 125 levels were measured. RESULTS: There was a significant difference between the resistance index value (0.692 +/- 0.188) in benign tumors and the value (0.503 +/- 0.107) in malignant tumors (P < .05). When 0.72 (mean of the malignant tumor resistance index values + 2 standard deviations) was considered as the cutoff value of the resistance index, the sensitivity and specificity of the resistance index in detecting malignant ovarian tumors were 92.6 and 52.8%, respectively. These values did not differ significantly from those with transvaginal sonography diagnosis (sensitivity 85.2%, specificity 69.4%). The resistance index sensitivity was significantly higher than those with MRI diagnosis (66.7%) and CA 125 levels (59.3%) (P < .05); however, the resistance index specificity was significantly lower than those with MRI diagnosis (97.1%) and CA 125 levels (91.7%) (P < .05). CONCLUSION: Our results suggest that transvaginal Doppler ultrasound does not provide more useful diagnostic information than transvaginal sonography, MRI, and CA 125 for the differentiation of malignant from benign ovarian tumors. PMID- 1448261 TI - Comparison of clinical versus surgical staging systems in vulvar cancer. AB - OBJECTIVE: To compare prognostic information from the new surgical staging system of the International Federation of Gynecology and Obstetrics (FIGO) with the old clinical staging system for vulvar cancer. METHODS: One hundred six women with previously untreated squamous cell carcinoma of the vulva who underwent radical vulvectomies and inguinal lymph node dissections at the University of Oklahoma from 1971-1990 were considered eligible for this study. A retrospective chart review was conducted to assign surgical stage. The clinical and pathologic factors analyzed for survival included the clinical and surgical stage of disease, nodal status, tumor size, and lesion location. RESULTS: Overall 5-year survival was 64%. Forty-three patients had inguinal and femoral node metastasis with a 5-year survival of 38%, versus 87% for patients without nodal metastasis (P < .00001). An increased number of positive groin lymph nodes was associated with a poorer prognosis. Thirty-one patients had tumors of 2 cm or less in maximum diameter with no recurrences, versus 52% 5-year survival in the remaining patients (P < .001). Perineal involvement was identified in 24 patients, but did not significantly influence survival. CONCLUSION: Overall, the new classification system revised by FIGO for vulvar cancer staging places patients into more accurate risk categories. PMID- 1448262 TI - Surgical treatment of unexpected invasive cervical cancer found at total hysterectomy. AB - OBJECTIVE: To determine the proper management of patients found to have invasive cancer of the cervix on pathologic examination of a uterus removed for benign indications. METHODS: We report 18 patients undergoing hysterectomy who were found to have cervical cancer with invasion deeper than 3 mm and/or lymph vascular space involvement. None had gross residual tumor following simple hysterectomy. All patients underwent a second operation. Seventeen women underwent a radical parametrectomy, upper vaginectomy, and pelvic lymphadenectomy; one had pelvic and periaortic lymphadenectomy alone because of bilateral grossly positive obturator nodes. RESULTS: Median follow-up was 72 months. One of the 15 women without residual disease or nodal involvement at second operation had pelvic recurrence 66 months after therapy. Three patients with disease identified at radical surgery underwent tailored postoperative pelvic radiation, and two of these had pelvic recurrence. The overall actuarial 5 year survival for the 18 patients was 89%. Operative morbidity was comparable to that of patients undergoing primary radical hysterectomy. CONCLUSION: This study confirms that patients with unexpected invasive cervical cancer found at total hysterectomy can undergo radical re-operation with low morbidity and excellent cure rates. PMID- 1448263 TI - Adenocarcinoma in situ of the uterine cervix. AB - OBJECTIVE: To assess the diagnostic accuracy of cervical conization in women with adenocarcinoma in situ and to determine whether a select group of women could be managed by conization alone without hysterectomy. METHODS: We retrospectively reviewed 40 cases of cervical adenocarcinoma in situ diagnosed on cervical conization. RESULTS: Cervical conization revealed adenocarcinoma in situ alone in 15 women. Twenty-five women had adenocarcinoma in situ coexisting with squamous dysplasia (23) or microinvasive squamous cell carcinoma (two). Twenty-two women underwent hysterectomy after cone biopsy. Adenocarcinoma in situ was detected in the hysterectomy specimen in one of 12 women with uninvolved cone margins, versus seven of ten women with involved margins (P = .006); two of these seven women also had foci of invasive adenocarcinoma in the hysterectomy specimen. Conization was the only treatment for 18 selected women with adenocarcinoma in situ and uninvolved margins; all were relapse-free after a median interval of 3 years (range 1.5-5). CONCLUSIONS: Women with cervical adenocarcinoma in situ diagnosed by conization who have positive margins are at high risk of residual adenocarcinoma in situ and moderate risk of occult invasive adenocarcinoma; expectant management is not warranted. However, a cone biopsy with uninvolved margins can reliably guide subsequent therapy. Selected young women who desire preservation of fertility and have uninvolved margins probably can be managed by conization alone, but further study is required to establish the safety of this approach. PMID- 1448264 TI - Radical hysterectomy in obese women. AB - OBJECTIVE: To determine whether there is a significant difference in treatment outcome and acute and chronic complications in obese compared with non-obese women having radical hysterectomy for early-stage cervical cancer. METHODS: From 1970-1985, 320 women underwent a class III radical hysterectomy and pelvic lymphadenectomy for stage IB-IIA invasive cervical cancer at Duke University Medical Center. Forty-three of these women weighed at least 80 kg and had a body weight greater than 25% above their ideal predicted weight. These women were compared to 277 patients with normal weight for height. RESULTS: The median age, incidence of diabetes mellitus and hypertension, number of nodes removed at lymphadenectomy, disease-free survival, length of hospital stay, and serious surgical or medical complications were the same in the two groups. However, obese patients had a significantly higher estimated blood loss, greater incidence of transfusion, and longer operative times. CONCLUSIONS: Survival is not compromised and the incidence of serious complications is not increased in obese patients treated with radical hysterectomy, but the operative technique is more difficult, the procedure lasts longer, and the surgery is associated with greater blood loss. PMID- 1448265 TI - Maternal and neonatal outcomes after oxytocin augmentation in patients undergoing a trial of labor after prior cesarean delivery. AB - OBJECTIVE: To study the safety of oxytocin augmentation in patients having abnormal labors after a prior cesarean delivery. METHODS: We retrospectively analyzed a case series of women undergoing a trial of labor after a previous cesarean delivery from the University of California San Francisco perinatal data base. Women whose labors were augmented with oxytocin were compared to women with labor abnormalities managed without the use of oxytocin. A wide range of maternal and neonatal outcomes was compared. Only vertex singleton term deliveries were studied. RESULTS: From 1975-1990 there were 504 trials of labor, of which 185 (37%) had labor abnormalities; 62 of these 185 (34%) were augmented with oxytocin. Fifty-eight percent of the trials of labor ended in vaginal delivery. In patients since 1982, 73% delivered vaginally. Forty-six (74%) of augmented patients delivered vaginally. There were no maternal deaths, uterine ruptures, or hysterectomies. Estimated blood loss was slightly greater among augmented patients after controlling for mode of delivery (P < .05), but only by 50-100 mL on average. There was no difference in the need for maternal transfusion. Fetal trauma and fetal scalp blood sampling occurred more frequently (P < .05) in the augmented labors, but only in the subgroup delivered by cesarean. No increased risk was demonstrated by a comparison between patients receiving oxytocin and epidural anesthesia and patients with labor abnormalities receiving neither. CONCLUSION: Retrospective analysis supports the use of oxytocin and epidural anesthesia to augment abnormal trials of labor after prior cesarean. PMID- 1448266 TI - Labor induction in women at term with mifepristone (RU 486): a double-blind, randomized, placebo-controlled study. AB - OBJECTIVE: To determine the efficacy and safety of mifepristone as an induction agent for the initiation of labor or as a cervical ripening agent in women at term. METHODS: Our study group contained 120 women at term (after 37.5 weeks' amenorrhea) who had clear clinical indications for labor induction. They were randomized to receive either 200 mg of mifepristone or placebo on days 1 and 2 of a 4-day observation period, with labor induction planned for day 4. Eight patients, three treated with mifepristone and five receiving placebo, had to be excluded from the survey because they required cesareans for medical reasons (fetal distress or maternal complications) less than 12 hours after taking the first tablet. RESULTS: Forty-one subjects entered spontaneous labor, 31 treated with mifepristone and ten in the control group (P < .001). Forty-five needed cervical maturation with prostaglandins on day 4, 13 of whom had received mifepristone and 32 of whom had been given placebo (P < .001). Thirteen women treated with mifepristone and 13 who had taken placebo had mature cervices sufficient for classic labor induction with oxytocin and amniotomy. Patients who delivered vaginally needed a much lower amount of oxytocin when mifepristone had been given, and the mean time interval between day 1 of the survey and the onset of labor was also significantly shorter in this group. CONCLUSION: Although more studies are needed, we have found mifepristone to be a safe, efficient, and suitable induction agent for initiation of labor in women at term. PMID- 1448267 TI - Psychosocial correlates of drug and heavy alcohol use among pregnant women at risk for drug use. AB - OBJECTIVE: To investigate the roles of life stress, depression, and social support in the use of drugs and alcohol among pregnant women at risk for substance use because they have a substance-using partner. METHODS: This is a secondary analysis of data collected for a study of the impact of health behaviors and psychosocial characteristics on the newborns of 1226 pregnant women. Participants were interviewed during pregnancy and postpartum using a questionnaire that included instruments such as the Life Experiences Survey, the Center for Epidemiologic Studies Depression Scale, and the Norbeck Social Support Questionnaire. Drug use by women was determined by self-report and urine toxicology screens. Drug use by partners was based on maternal report. RESULTS: Five hundred seventy-three women reported that they had a substance-using partner. These women were nearly five times more likely (odds ratio 4.87, 95% confidence interval 3.76-6.30) to be substance users compared with women who did not report substance use by a partner. Of these women, substance users reported more negative life events on average in the past year than did non-users (19.3 versus 15.8; P = .01). There was no difference in mean Center for Epidemiologic Studies Depression Scale scores (19.7 versus 18.7; P = .26) or in mean social support scores (78.2 versus 72.4; P = .14) between users and non-users. CONCLUSIONS: Women with substance-using partners have an increased likelihood of being users themselves. Among women with substance-using partners, substance use by a pregnant women is associated with more negative life events but not with depression symptomatology scores or social support scores. PMID- 1448268 TI - Crack cocaine: a risk factor for human immunodeficiency virus infection type 1 among inner-city parturients. AB - OBJECTIVE: To define the relationship between crack cocaine use and human immunodeficiency virus (HIV) infection while controlling for other HIV risk factors. METHODS: We performed a case-control study among inner-city pregnant women who were followed at a large urban hospital in Atlanta, Georgia; 79 of the women were HIV-1-infected and 525 were seronegative. We identified the women from a prenatal population undergoing routine voluntary HIV-1 antibody screening. RESULTS: From July 1, 1989 to December 31, 1990, we screened 13,469 pregnant women; 80 (5.9 per 1000) were HIV-1-infected. One seropositive woman who did not complete a risk-behavior questionnaire was excluded from the study. Seropositivity was associated with a history of crack cocaine use (odds ratio 2.3, 95% confidence interval [CI] 1.1-4.8), intravenous drug use (odds ratio 14.5, 95% CI 4.5-46.3), and a history of sexually transmitted diseases (odds ratio 2.6, 95% CI 1.5-4.5). We found a significant interaction (P = .01) between a history of crack cocaine use and employment status: Unemployed women who used crack cocaine were 3.5 times more likely to be HIV-1-infected than were employed women who used crack cocaine. CONCLUSIONS: Crack cocaine use was found to be a risk factor associated with HIV-1 infection among pregnant women, particularly those who were unemployed. This finding suggests that the impact of crack cocaine use on HIV transmission may be related to economic factors and possibly to either trading sex for money to buy cocaine or trading sex for the drug. PMID- 1448269 TI - Management and therapy of human immunodeficiency virus-infected pregnancies in maternal-fetal medicine fellowship training programs. AB - OBJECTIVE: To determine attitudes and practices of obstetricians in maternal fetal medicine fellowship programs regarding the management of human immunodeficiency virus (HIV) infection and the use of zidovudine during pregnancy. METHODS: We sent a questionnaire to the directors of all 78 approved maternal-fetal medicine fellowship programs. The responses, reflecting the consensus of the staffs of each program, were obtained and tabulated. RESULTS: Although their programs annually provide care for more than 2100 pregnant women infected with HIV, less than 25% of all maternal-fetal medicine fellowship directors reported that their patients participate in multicenter studies of HIV infection complicating pregnancy. Nearly two-thirds of the infected women are excluded from such multicenter studies. More than 70% of all program directors believe that zidovudine should be offered to symptomatic pregnant women infected with HIV; one-half question whether zidovudine poses short-term fetal risks. Nevertheless, nearly half of all HIV-infected pregnant women they manage are excluded from trials of zidovudine therapy during pregnancy. CONCLUSIONS: Many HIV-infected pregnant women who receive care in clinics of maternal-fetal medicine fellowship programs are excluded from multicenter studies. Consideration should be given to creating a national registry for this important, currently unreported, clinical resource. PMID- 1448270 TI - The epidemiology of pregnancy complications and outcome in a Norwegian twin population. AB - OBJECTIVE: To measure the contribution of genetic factors to selected pregnancy complications, including miscarriage, twinning, hypertension-toxemia, and nausea vomiting. METHODS: Information on 22,241 pregnancies of 8675 female twins or spouses of male twins was obtained by questionnaire from members of the population-based Norwegian Twin Panel. Comparisons of observed tetrachoric correlations were used to assess the importance of genetic influences on the variables examined. RESULTS: Pregnancy history information was provided by both members of 830 monozygotic and 902 dizygotic female twin pairs and by the spouses of both members of 459 monozygotic and 464 dizygotic male twin pairs. The incidence of twin pregnancy in general, and of opposite-sexed twins in particular, found among dizygotic twin women was nearly twice that observed for any other group. Monozygotic female twin pairs were more concordant than dizygotic female twin pairs for the occurrence of miscarriage, nausea or vomiting during pregnancy, and hypertension or overt toxemia. A similar pattern of twin similarity was observed for the use of certain medications during pregnancy including vitamins, aspirin, and nausea medication. CONCLUSIONS: Maternal genetic factors make an important contribution to a predisposition for dizygotic twinning, contribute to the risk of miscarriage, and appear to determine, in part, whether a woman experiences nausea-vomiting or hypertension-toxemia during pregnancy. In addition, health-seeking behaviors of women during pregnancy, as reflected by the use of several classes of medication, appear to be influenced somewhat by genetic factors. PMID- 1448271 TI - Color Doppler flow as an indicator of trophoblastic activity in tubal pregnancies detected by transvaginal ultrasound. AB - OBJECTIVE: To evaluate the potential benefits of transvaginal color Doppler in the diagnostic evaluation of tubal pregnancies. METHODS: Fifty-two women with suspected tubal pregnancy were examined by transvaginal ultrasonography and color Doppler. Those with positive scans were referred for exploratory laparoscopy. The area of the tubal pregnancy was examined by color flow imaging and the resistance indexes (RIs) of the artery blood flows were calculated. The pulsatility indexes (PIs) of both uterine arteries were also measured and serum beta-hCG was quantitated. RESULTS: Tubal pregnancy was diagnosed by transvaginal ultrasonography in 38 of the patients. There were two false-negative and two false-positive results. Color flow in the trophoblastic tissue was detected in 50% of the tubal pregnancies, and the mean (+/- standard deviation) RI of the trophoblastic flows was 0.51 +/- 0.12. The RIs of the trophoblastic flows tended to decrease at higher beta-hCG levels, and 88.2% of the cases with detectable trophoblastic flow had beta-hCG above 800 mIU/mL. The average PI of the uterine arteries was 2.28 +/- 0.89. The PIs of the ipsilateral uterine arteries were significantly lower in the patients with trophoblastic flow than in those without it. CONCLUSION: By monitoring trophoblastic activity, color Doppler may differentiate between active and inactive disease and could assist in choosing the correct treatment. PMID- 1448272 TI - [Importance of prognostic factors in the prognosis of cancer of the endometrium]. AB - 126 stage I and II endometrial cancer patients were followed up for at least 5 years to evaluate the impact of surgical-pathological risk factors on the survival. Out of the prognostic variables evaluated the age and clinical stage failed to influence the 5-year survival rate. The effect on survival of factors such as low grade of differentiation and the depth of myometrial infiltration was however significant, (p < 0.01 and p < 0.001 respectively). The early local recurrence has also significant negative prognostic value (p < 0.05). This latter can be effectively prevented through the prehysterectomy suture of the external cervical os. On the basis of their findings authors suggest to consider the grade and the depth of myometrial invasion beside the clinical stage at the determination of the extension of the surgical procedure and at the decision on the administration of postoperative irradiation. PMID- 1448273 TI - [Biochemical, clinical and genetic analysis of various aminoacidopathies (non ketotic hyperglycemia, maple syrup urine disease, histidinemia, tyrosinemia)]. AB - The genetical types were classified according to the clinical findings and biochemical results in cases of 13 newborn/children suffering from various aminoacidopathies. The genetical types were: 3 neonatal and 4 infantile types were found out of 7 non-ketotic disease (MSUD) patient was infantile type with 9.1 per cent keto acid decarboxylase activity in leukocyte homogenate. Among the 3 histidinemic patients 1 was severe neonatal type and 2 cases were chronic types. The 2 treated tyrosinemic children proved to be type III. (chronic with rickets). PMID- 1448274 TI - [Quality control of radiographic imaging of the lumbar spine]. AB - The qualitative control of the roentgenographic findings was performed independently by the assessment of five x-ray specialists on 40 two-directional lumbosacral roentgenograms. The findings were based on questioners including all details and a table of the internationally used "Radiological Diagnosis". In earlier publications the anatomical and structural changes were considered the risk factors of the waist. (Osteoporosis, changes in the position of the vertebral body, change in the shape of the spine, restriction of the intervertebral cleft and deformation of the small articulations). The views of the research workers were compared by means of statistical analysis. Compared with other authors the methods of these findings are in agreement with the international norms. These findings drew attention to the necessity of an objective assessment of the subjective findings. PMID- 1448275 TI - [Andrologic significance of genital mycoplasma]. AB - The authors investigated the effect of genital mycoplasma infection of fertility. The rate of silent mycoplasma infection was studied in asymptomatic andrological patients (655 persons) and in a control group of so called "chronic prostatitis" (1085) patients with clinical symptoms. In the asymptomatic andrological group the urethral smear was positive in 12.5% of cases, the ejaculate in 22.0% of cases. In the "chronic prostatitic" group mycoplasma infection was present in urethral smear in 34.8% of cases, and in the ejaculate in 37.0% of cases. The isolation showed that 29.2% of positive ejaculate samples contained M. hominis, and 70.8% of samples was infected by U. urealyticum. For investigating the effect of mycoplasma infection on the male fertilization capacity, infected and non infected andrological patients was compared by conventional andrological parameters and by modern functional tests like bovin mucus penetration test, hypoosmotic swelling test and swim up procedure. All the modern parameters and one of the conventional tests (sperm motility) showed a significant difference between the two groups. PMID- 1448276 TI - [Yersinia-induced arthritis in patients with spondylitis ankylopoietica of 20 year duration]. AB - The case of a 46 years old woman with spondylitis ankylopoetica is reported. Following diarrhoea a severe, asymmetric oligoarthritis developed with positive Yersinia enterocolitica serology. The acute oligoarthritis repressed after 2 month. PMID- 1448277 TI - [Centenary of the birth of Imre Haynal, M. D]. PMID- 1448278 TI - [Remembering Istvan Csapody (1892-1979)]. PMID- 1448279 TI - [HIV screening of milk donors]. PMID- 1448280 TI - [Endoprostheses for stenosis of the major airways]. PMID- 1448281 TI - A.C. and D.C. motility of mammalian auditory sensory cells--a new concept in hearing physiology. AB - Transduction of sound events results mechano-electrically in a.c. and d.c. movements of the auditory sensory cells based on de- and repolarization steps through the opening of apical and lateral K(+)--conductive ion channels. During transduction, apical ionic channels are thought to allow an influx of K+ resulting in a depolarization of the outer cell membrane. This is followed by a K(+)--efflux through basolateral K(+)--channels, inducing a re- or hyperpolarization phase. Different hypotheses expect the apical transduction channels to be located either in the cell membrane of the stereocilia and/or in the cell membrane of the cuticular plate (CP). Patch-clamp techniques revealed the presence of an unspecific CP-channel adjacent to the insertion of the stereocilia. In the basolateral cell membrane of outer hair cells (OHC) from the mammalian cochlea, the prevailing channel type, a rectifying high-conductance K(+)--channel, has been characterized as C-channel. After depolarization of the auditory sensory cells, however, the signal transfer divides at this point. The depolarization of inner hair cells (IHC) leads to the release of afferent transmitters for which glutamate is a good candidate. By contracts in OHCs the stimulation induces active mechanical responses of the sensory cells. Slow d.c. movements of the cylindrical hair cell body as well as of the cuticular plate with the sensory hairs are thought to control the operation point of the stereocilia. The mechanical characteristics of the cochlear partition during adaptation, TTS as well as the homeostasis of the basilar membrane location could be modulated by the OHCs. In particular, the slow d.c. movements may protect the vulnerable cochlear partition against high sound pressure levels. Rapid d.c. movements of which the underlying mechanisms is unknown, may interfere cycle-by cycle with the travelling wave. Thus, near hearing threshold, they could drastically amplify and tune the travelling wave. This could explain otoacoustic emissions, the high sensitivity and the frequency selectivity of the ear at low sound pressures. Moreover, it cannot be excluded that the actomyosin skeleton significantly helps to amplify the travelling wave by intermittent stimulations of a resonance system. PMID- 1448282 TI - [Etiology of laryngeal neoplasms--results of epidemiologic tests in Upper and Lower Silesia]. PMID- 1448283 TI - [One stage reconstructive surgery of the hypopharynx from clinical material of the ENT Clinic Medical Academy in Cracow]. AB - From April 1990 till September 1991 in ENT Clinic Medical Academy in Cracow 6 patients with well advanced laryngeal cancer involving hypopharynx were treated surgically. Total laryngectomy with partial or total hypopharyngectomy was performed and then the reconstruction of hypopharynx one stage procedure using pectoralis major myocutaneous flap was done. In all patients cosmetic and functional results were excellent. PMID- 1448284 TI - [Evaluation of frequency of recurrence in malignant head and neck neoplasms in the years 1980-1990]. AB - During the years 1980-1990 in the Otolaryngological Department of the Silesian Medical Academy in Katowice 452 patients with malignant neoplasms of the head and neck were treated. 154 (35%) patients treated by radiotherapy. 140 (30%) were operated, 133 (29%) were treated by both methods and 25 (6%) were treated symptomatically. 139 (30%) out of them have had the recurrencies after the treatment. The authors made the analysis of frequency of recurrencies in years 1980-86 in comparison with period 1987-90. The statistically significant increase of frequency of recurrencies in years 1987-1990 was found. PMID- 1448285 TI - [Histologic grading of malignancy and prognosis in laryngeal neoplasms]. AB - The semi-quantitative grading system for squamous cell carcinoma based on estimation of multiple histologic variables according to Jakobsson is presented. Selected histologic parameters have been also evaluated regarding their importance in predicting patient outcome. Features such as differentiation of the tumor cells, their nuclear polymorphism, number of mitoses and vascular invasion significantly correlated with clinical outcome. The structure of the tumor and cellular host response had no influence on survival. There was statistically significant relationship between the patient outcome and histologic grade of malignancy expressed by total point value. The incidence of cervical node and distant metastases was three times more frequent in the group of poorly differentiated tumors than in others. There was no correlation found between the localization of the tumor and the degree of cancer differentiation, but the supraglottic tumors poorly and moderately differentiated infiltrated towards the glottis more often then highly differentiated. PMID- 1448286 TI - [Partial supra-cricoid reconstructive laryngectomy with CHP and CHEP: surgical technique and oncologic results]. AB - The authors present a report on 62 cases of partial horizontal supracricoid reconstructive laryngectomy, including 28 cases of cricohyoidopexy (CHP) and 34 cases of cricohyoidoepiglottopexy (CHEP). The surgery was carried out in the years 1971 to 1989 in the ENT Clinic of Pomeranian Medical Academy in Szczecin. The indications, surgical technique and oncological results are presented. 78% patients survived after 3 years and 73% after 5 years without recurrence. The reasons of failure and the way of treatment are discussed. PMID- 1448287 TI - [Interleukin-1 beta and TNF alpha in serum of patients with otosclerosis]. AB - Levels of interleukin-1 beta and tumor necrosis factor--alfa were determined using immunoradiometric method in the serum of patients who have gone surgical treatment due to otosclerosis. Values of both cytokines were higher in the serum of patients as compared with the control group. As regards TNF-alfa these differences were statistically significant. PMID- 1448288 TI - [Effect of equilibrium disorders in otosclerotic patients post stapedectomy on postoperative hearing improvement]. AB - In this paper author described the significance of vestibular symptoms post stapedectomy in postoperative hearing improvement. Vertigo post stapedectomy was noted and spontaneous nystagmus, positional nystagmus and directional preponderance were examined. Postoperative hearing improvement in patients with and without vestibular symptoms was compared. Author maintained that recent symptoms of peripheral vestibular disfunction had made no difference in postoperative hearing improvement. PMID- 1448289 TI - [An objective evaluation of retrocochlear structures in the auditory pathway by means of CNT (cochlear nerve tester)]. AB - Indications for hearing implants in profoundly deaf patients have been presented. Auditory pathway status was evaluated by application of electrical stimulation of cochlear nerve. The electrical stimulus originated from Cochlear Nerve Tester. Obtained sound sensations might be revealed on ABR pattern. PMID- 1448290 TI - Diagnostic value of transtympanic electrocochleography; case reports. AB - The transtympanic electrocochleography is performed on more than 1000 patients with various hearing loss. The registration technique in brief as well as some interesting findings (endolymphatic hydrops, neural hearing loss due to multiple sclerosis, mitochondrial cytopathology) will be presented. The indications of the electrocochleography as an audiological topo-diagnostic tool will be discussed. PMID- 1448291 TI - Auditory brainstem responses (ABR) in guinea pigs to loud tones noise: a preliminary study. AB - It is well known that exposure to intense acoustic stimuli can induce permanent damage to the tissues of the inner ear. In this study the technique of ABR measurement and the experimental animal model of acoustic trauma were presented. In forty 3 months old guinea pigs the hearing threshold was assessed using the ABR technique (Amplaid mk 10 system). The hearing thresholds ranged from 40 to 50 dB-pe-SPL (mean 45.26 dB, sd. 4.73). The mean latencies of the four most prominent peaks in the ABR pattern were also measured. Fourteen of animals were then exposed to a 1 kHz pure tone at different duration and stimulus level. The ABR threshold was measured immediately after exposure and 20 to 30 days later. The exposure at 112 dB for 2h caused the threshold shift in all guinea pigs varying from 25 to 65 dB. After 3-4 weeks of recovery time in all animals hearing threshold improved, in some animals reaching the pre-exposure level. We conclude that the ABR technique allows to measure precisely and with high reproducibility the hearing level in guinea pigs and also allows to estimate the threshold shift after exposure to noise. PMID- 1448292 TI - [Wladyslaw Oltuszewski--organizer of the first Polish phoniatrics institute (in it's 100 year anniversary)]. AB - On the occasion of 100's anniversary of first phoniatrics' department foundation in Poland--"The Warsaw Institute of Speech Deviation", the activity of dr med. Wladyslaw Oltuszewski its organizer and the pioneer of Polish phoniatrics is described. The main topics of his activities are referred in his book "About speech and its disorders" (1906). Dr Oltuszewski's achievements in the popularization of the knowledge about speech disorders were strongly pointed out. His lectures were given not only for medical societies but also for the pedagogic ones. PMID- 1448293 TI - [Malignant tumors of the head and neck in children. Part I--review]. AB - About 27% of malignant tumors in children is located in the head and neck. Besides primary solid tumors, lymph node metastases as well as signs of systemic diseases of the lymphatic tissue are often found in this region. The latter are the most common childhood malignancies. Among primary solid malignant tumors in this region neoplasms of the soft tissues are frequency found. Their prevalence comes next to the tumors of the central nervous system and the orbit. Rhabdomyosarcoma (RMS) represents 50% of cases in this group. Malignant neoplasms originating from epithelial and bone tissue occur rarely in children. The evolution of triple therapy, combining surgery with irradiation and chemotherapy has produced and improvement in prolonged survival rates in these children. PMID- 1448294 TI - [State of the vestibular system in chronic alcoholics]. PMID- 1448295 TI - Interdisciplinary treatment of spina bifida children. AB - In the Spina Bifida Centre, Niguarda Ca' Granda Hospital (Milan, Italy), from June 1985 to June 1990, 60 spina bifida children have been treated. The results of the rehabilitation programme (including orthopaedic, urological and psychosocial aspects) at the time of the survey were: (a) Neuromotor function: 72% of the patients achieved ambulation, 52% of these being less than 2 years of age, and 20% older than 2 years; 18% were too young for walking. Thus, considering the children's age, about 90% of the subjects achieved the standing position, and 89% achieved ambulation. (b) Bladder function: 83% of the children had a complete urological evaluation; 40% of those with a neuropathic bladder had a hyperreflex type, 54% areflexic, and 6% normoreflexic. Thirty-two percent of the patients had signs of 'high pressure' bladder function. Urinary continence was: 36% > or = 2 hours, 20% < 2 hours, 44% not detectable (age < 2 years). Forty percent of the subjects used intermittent catheterisation. (c) Psychosocial aspect: child adaptation to the disease and to the rehabilitation programme was good in 61% of the patients; family problems were identified in 70% of the patients; enrollment in preschool and school programmes was normal (or with specialist teaching) in about 74%; 33.3% of the subjects had disturbance of affect. The results clearly showed that the interdisciplinary approach favoured the social integration of these children. PMID- 1448296 TI - Spinal cord injury: 10 and 15 years after. AB - Researchers have only recently begun to study the problems and adaptations of persons who have lived with spinal cord injury (SCI) for many years. This descriptive study examined recent functional changes and perceptions regarding the quality of life in 43 SCI persons who were 10 or 15 years post injury; 31 percent of the 137 persons surveyed (by mail) responded. On a general rating of quality of life, neither level nor completeness of injury was a significant factor. Subjects who were in a preferred current living situation had a significantly better perceived quality of life (t = -3.2, p < .01); employment did not similarly affect quality of life ratings. There was no significant Spearman correlation between quality of life and the number of recent changes experienced in daily functioning (rs = .17); likewise, quality of life was not related to involvement in exercise or other recreational activities. The nature of the changes most often experienced, as well as factors that persons saw as helping to maintain their independence, are described. PMID- 1448297 TI - Depressed serum high density lipoprotein cholesterol levels in veterans with spinal cord injury. AB - Cardiovascular diseases are the most frequent cause of death among persons with spinal cord injury (SCI), and these diseases are reported to occur prematurely in the disabled compared to the able bodied population. The mechanism of accelerated coronary heart disease (CHD) in persons with SCI may be partially explicable on the basis of the lipoprotein profile. We performed fasting lipoprotein determinations on 100 veterans with SCI, 50 with paraplegia and 50 with quadriplegia, and 50 veteran controls. The mean age of the subjects with SCI was 47.8 +/- 1.4 years with a duration of injury of 16.3 +/- 1.2 years. The mean serum high-density lipoprotein (HDL) cholesterol was depressed in subjects with paraplegia or quadriplegia compared to controls (37 +/- 1 or 40 +/- 1 versus 48 +/- 2 mg/dL, p < 0.0001). Although serum total cholesterol was lower (p < 0.01) in subjects with SCI than in controls, there was no significant difference in mean serum low-density lipoprotein (LDL) cholesterol. Thirty-seven percent of subjects with SCI have serum HDL cholesterol levels less than 35 mg/dL with no significant difference in lipoprotein distribution between high and low cord lesions. Eighteen percent of individuals with SCI have an absolute elevation of LDL cholesterol (greater than 160 mg/dL). About 40% of those with SCI and LDL cholesterol levels between 130 and 160 mg/dL also have serum HDL cholesterol values below 35 mg/dL, all of whom would have their serum HDL cholesterol level undetected if lipoprotein profiles were performed according to present recommendations--that is, only if the serum total cholesterol is elevated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448298 TI - Suggested MRI criteria for surgical decompression in acute spinal cord injury. Preliminary observations. AB - The effect of spinal cord compression identified with magnetic resonance imaging (MRI), on neurological prognosis, was retrospectively evaluated in 36 patients with acute spinal cord injury. Of the 21 patients without cord compression, 16 had potentially reversible injury (normal spinal cord or cord oedema), all having functional recovery. Of the 15 patients with cord compression, 3 had operative decompression. In the 12 patients who did not undergo surgery, the degree of recovery was directly related to the magnitude of spinal cord compression, only one of the patients with moderate or marked cord compression having useful motor function at follow up. In contrast, the 3 patients with surgical decompression had at least 2 grades of improvement, all having functional recovery. These findings raise the possibility that MRI may be used to identify a patient group who will benefit from surgical decompression. A numerical index is proposed to prospectively identify patients for surgical decompression, and further studies are underway to evaluate this. PMID- 1448299 TI - Bacterial biofilm formation in the urinary bladder of spinal cord injured patients. AB - Ten spinal cord injured patients aged 8 to 55 years (mean 32) were followed for up to 2 months after admission to a rehabilitation setting from an acute care hospital. Urinary fluid and bladder epithelial cells were collected weekly by intermittent catheterization and examined for bacterial colonization. Six patients had no history of urinary tract infection upon admission, likely due to the antimicrobial coverage given during acute care. All the patients subsequently became colonized with uropathogens at some time during the study period. Bacterial biofilms were found in 73% of the samples (73% Gram negative organisms, 27% Gram positive), with mean pathogenic adhesion counts of 29 organisms per bladder cell. In 16% of cases, bladder biofilms were found when urine culture was negative. Bacterial biofilms were also evident during antimicrobial therapy in 10 of 12 samples tested and urine cultures showed breakthrough infections in 50% of cases. Two asymptomatic patients were colonized with Klebsiella pneumoniae and Pseudomonas aeruginosa and were dismissed without requiring therapy. Clearly, bacterial biofilms can exist on bladder epithelia, without being detected in urine samples and without giving rise to symptoms. The extent to which they occur and damage the host remains to be determined, as does the answer to the question, should these patients be treated? PMID- 1448300 TI - Results of the combined treatment of paediatric intraspinal tumours. AB - In this article 98 patients with paediatric intraspinal tumours are presented. All were evaluated according to their ages, sex, signs and symptoms. The patients also had radiological and histopathological studies; and the results of surgical, physical medicine and rehabilitation and of radiotherapy are discussed and compared with the results of patients reported in the literature. PMID- 1448301 TI - Lumbar spine dimensions in paraparetic patients: a 10 year follow up study. AB - Lumbar spinal AP radiographs of 13 C3-T11 paraparetic patients taken at about a 10 year interval were compared. The height (H) and maximum width (W) of the interapophysolaminar spaces (IALS), the width of the vertebral bodies at their waist (V) and the relationship between them showed minimal change over the follow up period. The difference between the late and early mean IALS height values increased caudally but was statistically significant only below L5. Subjective evaluation of the consecutive x-ray films revealed few new degenerative abnormalities. It is concluded that the normal aging process, which includes horizontal spreading of the lumbar vertebral bodies and narrowing of the lumbar spinal canal, is not accelerated by paraparesis and may even be retarded by relative immobilization. PMID- 1448302 TI - Postoperative wound infections following myocutaneous flap surgery in spinal injury patients. AB - Severe pressure ulcers in patients with spinal cord injury are frequently treated by using musculocutaneous (m-c) flap surgery. There have been few studies of the use of perioperative antibiotics to prevent postoperative infection in this setting. We reviewed 74 m-c flap surgeries in 53 patients (41 male and 12 female) from October 1989 for one year. The sites involved were ischial (31), sacral (24), trochanteric (18), deltoid (2), olecranon (1) and posterior thigh (1). An antibiotic was usually administered perioperatively for 5 days. Patients were followed for a median of 30 (8-96) weeks. Postoperative infections occurred at a median of 12 (4-25) days in 6 of 74 (8%) surgeries. The organisms cultured from the 6 infected wounds were: Bacteroides sp. (4), Proteus mirabilis (2), E. coli (2), MRSA (2), and others (6--each isolated once). These results indicate that antibiotics did not prevent postoperative infection in approximately 8% of patients undergoing m-c surgery. The frequency of isolation of Bacteroides sp. from these infections suggests that anaerobic bacteria may persist in healing pressure ulcers and perioperative antibiotics might include coverage for anaerobic bacteria. PMID- 1448303 TI - Incidence and risk factors in the appearance of heterotopic ossification in spinal cord injury. AB - Heterotopic ossification (HO) is a frequent complication in patients with a spinal cord injury (SCI), although the aetiology is unknown. A study was undertaken of 654 SCI patients with traumatic aetiology, admitted for the first time to the Hospital Nacional de Paraplejicos, Toledo, during 1988 and 1989. Of the total number of patients, 85 (13%) were diagnosed HO and 569 without HO. The diagnosis was mainly achieved by x-ray studies and clinical signs. From the 569 patients with traumatic aetiology without HO, 44 were selected at random, as were 44 of the 85 patients with HO. The mean time lapse between the occurrence of the accident and admission for patients with HO was 40.79 days (typical deviation (TD) = 45.2), and for patients without HO was 32.84 (TD = 38) days, resulting in a value of F = 0.796 through analysis of variance, which is not a statistically significant variation between the 2 groups. In both groups we have taken account of the following variables: age at time of lesion, lesion level, type of lesion (complete or incomplete), spasticity, urinary tract complications, deep vein thrombosis, important associated injuries occurring at the moment of lesion, time elapsed before admission and the existence of pressure sores. In those SCI patients with HO the number of ossifications and their localisations were also verified. By use of the chi square test (X2) over all 9 variables which were studied, we found that 3 variables (complete spinal lesion, presence of pressure sores and spasticity) were significantly related to HO formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448304 TI - Use of the biceps femoris following failed inferior gluteal flap transfer. Case report. AB - Considering the high recurrence rate of pressure ulceration in paraplegic patients, flap procedures to reconstruct a defect should not be at the expense of another possible future flap. The posterior thigh fasciocutaneous flap is useful for the coverage of ischial and trochanteric pressure sores; the biceps femoris musculocutaneous flap is a useful choice for deep ischial defects. However, the cutaneous portions of these two flaps is nearly identical. The previous transfer of the biceps flap excludes the further use of the posterior thigh flap. In contrast, use of the posterior thigh flap still permits the employment of a biceps V-Y advancement flap. Even if the donor site of the previous posterior thigh flap must be skin-grafted, the graft will remain viable on its muscular bed and function as the cutaneous portion of the flap; thus stable coverage is provided, despite previous use of 'first line' flaps. We demonstrate how careful planning of the stages of flap procedures can allow the most economic use of donor areas in this difficult patient group. PMID- 1448305 TI - Urinary lithiasis induced by sulfamethoxazole in a patient with tetraplegia. Case report. AB - Bladder lithiasis is a frequent complication in paraplegics and tetraplegics. We report on a patient where treatment of a urinary infection with antibacterial sulfamides was the causative factor in the formation of bladder stones. PMID- 1448306 TI - Duration of symptoms and outcome in bacterial meningitis: an analysis of causation and the implications of a delay in diagnosis. AB - The prompt diagnosis and therapy of bacterial meningitis remain enduring clinical challenges, for no physician would knowingly delay appropriate therapy. However, whether a delay in the initiation of antimicrobials in fact causes a worse outcome is a separate and tangential question. In clinical medicine a treatment decision involves a bedside estimate of the risk and potential severity of illness balanced against the benefits and adverse effects of therapy. For severe infections, the inexorable damage of untreated disease is presumed, and antimicrobials properly are given without hesitation. In contrast the methodical weighing of evidence regarding the issue of causation is for the purpose of characterizing biologic phenomena. Although legal and medical implications may be contained in such an analysis, its relevance to any particular clinical case is only retrospective. To judge responsibly the strength of a causative link, all available scientific evidence must be analyzed by established criteria. Such as analysis suggests that any connection between a delay in the treatment of bacterial meningitis and outcome depends on the presenting clinical pattern. If the presentation is that of a nonspecific illness with general symptoms, then a short delay of < 3 to 5 days does not appear to alter the risk of sequelae or death. In the case of fulminant meningitis a delay in initiating therapy seems unconnected to outcome. Finally for patients with a history of clinically overt meningitis, an inappropriate delay in commencing therapy incrementally increases the risk of permanent injury. PMID- 1448307 TI - Therapy of bacterial sepsis, meningitis and otitis media in infants and children: 1992 poll of directors of programs in pediatric infectious diseases. AB - To determine current opinions among experts in pediatric infectious diseases for treatment of bacterial sepsis, meningitis and acute otitis media, we polled directors of training programs in January, 1992. Responses were received from 69 centers in the United States and Canada. For initial treatment of presumed bacterial meningitis, the third generation cephalosporins alone or combined with ampicillin have become drugs of choice in all age groups. Most infectious disease programs include dexamethasone in the management of presumed bacterial meningitis for children 2 months of age and older. Third generation cephalosporins are also drugs of choice for presumed sepsis: combined with ampicillin for infants 5 weeks of age; used alone for children 5 months and 12 years of age. Amoxicillin remains the preferred drug for initial treatment of acute otitis media. The combination of amoxicillin and clavulanic acid is favored in the setting of an increased proportion of beta-lactamase-producing bacterial pathogens. Comparison of these results with polls in 1987 and 1989 indicates a shift in recommendations of therapy of presumed bacterial sepsis and meningitis from ampicillin alone or combined with an aminoglycoside or chloramphenicol to use of a third generation cephalosporin alone or combined with ampicillin. PMID- 1448308 TI - Missed opportunities for influenza vaccination among children with asthma. AB - Influenza vaccination is recommended for children with moderate to severe asthma. However, most children with asthma are not vaccinated, in part because many do not make an office visit during the vaccination time period. We studied 247 urban children with asthma to determine the maximum number that could have been vaccinated during a medical visit to a clinic or emergency department. One hundred thirty-nine patients (56%) had at least one visit during the study period. Sixty-five patients (26%) received the influenza vaccination; 74 patients (30%) did not receive the vaccination despite being seen in the clinic or emergency department. One-half of the missed vaccination opportunities at the clinic occurred during nonacute visits. Influenza vaccination rates could be substantially improved by efforts to increase primary care visits during the vaccination time period and to minimize missed vaccination opportunities. PMID- 1448309 TI - Value of C-reactive protein determination in the initial diagnostic evaluation of the febrile, neutropenic child with cancer. AB - We studied prospectively the value of administration C-reactive protein (CRP) in the diagnostic evaluation of the child with cancer hospitalized for fever and neutropenia. During a 7-month period 74 patients with malignant disease had 122 hospital admissions because of fever and neutropenia. All patients had a serum CRP obtained 8 to 24 hours after the onset of fever as part of their initial evaluation. There was a borderline correlation between serum CRP concentration and temperature at admission (P = 0.06). Patients with fever without an identifiable source had significantly lower CRP concentrations compared with those having focal or microbiologically documented infection (34.9 +/- 6 vs. 70.2 +/- 12 mg/liter; P = 0.0005). Twelve patients had positive blood cultures, 5 of which were coagulase-negative staphylococci considered to be central venous catheter-related infection or colonization. CRP concentrations were significantly lower in these 5 patients compared with the 7 patients with septicemia caused by other organisms (21 +/- 9 vs. 113 +/- 23 mg/liter; P = 0.01). In distinguishing between septicemic and nonsepticemic children, serum CRP was found to have excellent sensitivity and negative predictive value at concentration limits of 20, 50 and 100 mg/liter. However, both specificity and positive predictive value were low at these respective levels, thus limiting the overall utility of serum CRP in the initial empiric management of the febrile, neutropenic child with cancer. PMID- 1448310 TI - Prophylactic miconazole oral gel for the prevention of neonatal fungal rectal colonization and systemic infection. AB - Prior rectal colonization with fungi may be an important risk factor for development of systemic fungal infection in the neonate. This placebo-controlled study evaluated the benefits of miconazole oral gel in the prevention of fungal rectal colonization and systemic infection in high risk neonates admitted to the Neonatal Intensive Care Unit. Repeated oral application of miconazole gel reduced the overall prevalence of postnatally acquired rectal colonization; a yeast was grown in 19.5% of the weekly rectal swabs in the miconazole-treated group compared with 36.2% in the control group (69 of 354 vs. 146 of 403, P < 0.0001). There was no reduction in the incidence of systemic fungal infection in the two groups although the overall incidence of the infection was low in both groups, at 2.0% vs. 2.6% (6 of 298 vs. 8 of 302, P not significant). No relationship was shown between prior rectal colonization and subsequent systemic fungal infections in either of the two groups. This study does not support the use of prophylactic miconazole oral gel for the prevention of neonatal systemic fungal infections. PMID- 1448311 TI - Comparative efficacy of oral rifampin and topical chloramphenicol in eradicating conjunctival carriage of Haemophilus influenzae biogroup aegyptius. Brazilian Purpuric Fever Study Group. AB - Persistent conjunctival carriage of the Haemophilus influenzae biogroup aegyptius (Hae) strain (BPF clone) responsible for Brazilian purpuric fever (BPF) has been documented. Topical chloramphenicol is routinely used to treat conjunctivitis in areas affected by BPF in Brazil. Although the BPF clone is susceptible to chloramphenicol, we observed a number of children treated with topical chloramphenicol for conjunctivitis who still developed BPF. During an investigation of an outbreak of BPF in Mato Grosso State, Brazil, we compared oral rifampin (20 mg/kg/day for 4 days) with topical chloramphenicol for eradication of conjunctival carriage of H. influenzae biogroup aegyptius among children with presumed BPF clone conjunctivitis. Conjunctival samples were taken for culture on the day treatment was initiated and a mean of 8 and 21 days later. At 8 days the eradication rates for oral rifampin and topical chloramphenicol were 100 and 44%, respectively (P = 0.003); at 21 days they were 100 and 50% (P = 0.01). Oral rifampin was more effective than topical chloramphenicol for eradication of the BPF clone and may be useful in prevention of BPF. PMID- 1448312 TI - Immunogenicity of recombinant hepatitis B vaccine in urban black children from Ga Rankuwa, Bophuthatswana, South Africa. AB - Many areas in Southern Africa have a relatively high endemicity for hepatitis B for which the only effective medical measure is vaccination. The aim of this study was to evaluate the antibody response to a recombinant hepatitis B vaccine (Engerix B; Smith Kline-Beecham) in a black urban population, with the use of the recommended regimen and a low dose, short course. One hundred eleven children seronegative for hepatitis B virus (5 to 19 years old) were randomized to receive one of the two vaccination schedules (20 micrograms at zero, 1 and 6 months or 2 micrograms at zero, 1 and 2 months). Antibody to hepatitis B surface antigen was determined 6 to 8 weeks after the last dose by radioimmunoassay (Ausab; Abbott Laboratories). The recommended schedule gave a seroconversion rate of 100% with a geometric mean titer of 585.9 mIU/ml. The low dose, short course schedule produced a seroconversion rate of 63.8% and a geometric mean titer of 73.8 mIU/ml. In the 5- to 9-year-old individuals, however, 71.6% seroconverted (geometric mean titer 114.2 mIU/ml). For cost reasons further investigations on low dose regimens are indicated. PMID- 1448313 TI - Diphtheria-tetanus toxoids-pertussis vaccination does not increase the risk of hospitalization with an infectious illness. AB - The purpose of this study was to determine whether children hospitalized with a primary diagnosis of infection were more likely than matched controls to have had a diphtheria-tetanus toxoids-pertussis immunization in the 30 days before hospitalization of the case. Cases were less likely than controls to have received an immunization (P = 0.003). They were also less likely to have been breast-fed (P < 0.001) and to have had a well-child care clinic visit (P = 0.01). Cases were significantly more likely to be preterm (< 38 weeks gestation), low birth weight (< 2500 g) and attending day care than their matched nonhospitalized controls (P = 0.003, 0.03 and 0.002, respectively). This study demonstrates no association between receipt of diphtheria-tetanus toxoids-pertussis immunization and subsequent hospitalization for an infectious illness. PMID- 1448314 TI - Gastric lavage is better than bronchoalveolar lavage for isolation of Mycobacterium tuberculosis in childhood pulmonary tuberculosis. AB - We compared the sensitivity of gastric lavage (GL) with bronchoalveolar lavage (BAL) for isolating Mycobacterium tuberculosis (Mtb) from 20 children with a presumptive diagnosis of primary pulmonary tuberculosis. GL was performed on three consecutive mornings after an overnight fast. BAL was performed on the same day as the last GL. Specimens were submitted for smears and culture for Mtb. None of the acid-fast stained smears was positive. Cultures of BAL fluid on 2 patients (2 of 20 or 10%) were positive for Mtb. Cultures of the gastric aspirates from the same 2 patients were also positive for Mtb. Eight additional patients had positive GL cultures with negative BAL cultures, resulting in a total of 10 of 20 (50%) patients with positive GL cultures for Mtb. The results of our study indicate that GL done on three consecutive days is better than BAL for the bacteriologic diagnosis of childhood pulmonary tuberculosis. PMID- 1448315 TI - Sepsis and septic shock: a review for clinicians. PMID- 1448316 TI - Infections in children with severe protein-energy malnutrition. PMID- 1448317 TI - Perinatal blastomycosis: a review. PMID- 1448318 TI - Lack of efficacy of the urine culture as part of the initial workup of suspected neonatal sepsis. PMID- 1448319 TI - Microbiology of scalp abscess in newborns. PMID- 1448320 TI - Group B streptococcal cellulitis-adenitis in a previously normal child. PMID- 1448321 TI - Chronic epiglottitis in a child with acquired immunodeficiency syndrome. PMID- 1448322 TI - Fever as an adverse reaction to oral trimethoprim-sulfamethoxazole therapy. PMID- 1448323 TI - Rotavirus encephalopathy: evidence of central nervous system involvement during rotavirus infection. PMID- 1448324 TI - Intestinal parasitism of children on Corn Island, Nicaragua. PMID- 1448325 TI - Haemophilus influenzae type B endocarditis and meningitis. PMID- 1448326 TI - Which gram-positive rod would you choose? PMID- 1448327 TI - Encephalitis: direct infection vs. immune-mediated. PMID- 1448328 TI - Vitamin C, neutrophils and the symptoms of the common cold. PMID- 1448329 TI - Decline of Haemophilus disease in Cleveland. PMID- 1448330 TI - Diagnosis and treatment of human immunodeficiency virus infection in infants. PMID- 1448331 TI - Expectant antibiotic therapy in an infant already immunized against Hemophilus influenzae type B. PMID- 1448332 TI - Diagnosis and management of meningitis. PMID- 1448333 TI - [Quantitative analysis of pneumoconiosis in standard chest radiographs]. AB - A computerized method to quantify and characterize interstitial diseases by using physical texture measures obtained from an analysis of the power spectrum of lung textures in digital chest radiographs was applied to Japanese standard radiographs of pneumoconiosis. Texture measures were determined from standard radiographs of silicosis, asbestosis, and other types of pneumoconiosis as well as chest radiographs of normal lungs. Our preliminary results indicated that the texture measures obtained from computer analysis corresponded closely with the standard categories of silicosis. However, there was no significant correlation between texture measures and the categories for asbestosis and other types of pneumoconiosis in terms of texture pattern. Japanese standard radiographs of pneumoconiosis are categorized according to the profusion of opacities, without reference to the size and shape of the opacities. Furthermore, in some films the size and shape of the opacities vary considerably within the same category. Therefore, it is considered that these characteristics of the standard films affected the results of our texture measures. It also considered that a large ROI and other texture measures are needed to characterize large opacities and mixed shaped opacities of pneumoconiosis. PMID- 1448334 TI - [Imaging diagnosis of lupus enteritis--especially about sonographic findings]. AB - We evaluated 4 cases of lupus enteritis by US, abdominal X-ray and CT. On US examinations, in particular, we observed ascites and edematous thickening of the small intestine where Kerckring folds with submucosal edema resembled an accordion. After steroid treatment and consequent improvement of the disease, we noticed disappearance of the intestinal thickening and ascites on US examination, compatible with the diagnosis of lupus enteritis. Based on these results, US was useful for the diagnosis and follow-up of lupus enteritis. PMID- 1448335 TI - [Assessment of a coaxial system accommodated to a 0.035 inch guide wire in superselective hepatic angiography and embolization]. AB - A special coaxial catheter system accommodated to a 0.035 inch guide wire was recently developed. The four-part coaxial system is composed of a central 0.035 inch flexible guide wire, a 4-French inner catheter (straight, 90 cm in length), a 6-French outer catheter (fork-shaped, 60 cm in length), and a hemostatic valve. The 4 French inner catheter is large enough in diameter to allow a larger volume of contrast medium and greater amount of embolic material than the earlier coaxial system. Using this coaxial catheter system, we performed successful superselective hepatic arteriography and embolization in 44 patients with malignant hepatic tumors. Catheterization of the celiac and superior mesenteric arteries with the 6 French outer catheter was easy, and the angiogram obtained was very distinct. The 4 French inner catheter was easily and safely advanced into the segmental hepatic artery, and even common hepatic arteriography with this catheter provided clear images on conventional cut films. Therefore, in most cases, both angiography and embolization can be accomplished using this coaxial system alone. PMID- 1448336 TI - [Intracranial MR imaging of achondroplasia]. AB - Intracranial MR imaging was performed in five patients with achondroplasia. All patients had narrowing of the subarachnoid space at the level of the foramen magnum that was mainly due to protrusion of the posterior aspect. Three patients had compressive deformities of the brainstem and/or upper cervical spine. Among them, two patients had deformities of the pons. Relative upward displacement of the brainstem was seen in all patients. Hydrocephalus was seen in three patients. PMID- 1448337 TI - [MR imaging of thyroid masses]. AB - Magnetic resonance (MR) imaging was performed in 35 patients with histologically proved thyroid masses. Gadopentetate dimeglumine was used in 25 of these cases. The thyroid tumors were analyzed by MR imaging as to shape, margin, pseudocapsulation, homogeneity, and enhanced pattern. Gd-DTPA was helpful in identifying pseudocapsules and showing the extent of the tumor. Papillary carcinoma tended to display unclear margins, heterogeneous intensity, and inhomogeneously enhanced patterns. In follicular adenoma, the tumor margin was smooth and pseudocapsules were clearly detected. Follicular adenoma was enhanced homogeneously, but it was difficult to distinguish follicular adenoma from follicular carcinoma by MR imaging. Adenomatous goiter was delineated as multiple nodules with smooth margins, but without pseudocapsules. These nodules were enhanced in various ways after Gd-DTPA administration. PMID- 1448338 TI - [CT-guided selective pneumomediastinography and its clinical evaluations]. AB - CT diagnosis is playing a central role in the judgment of mediastinal invasion in esophageal and pulmonary cancers. Estimation of the mediastinal invasion is now based on the indirect findings such as presence of a fatty layer and angle of contact between the lesion and adjacent organs. An attempt to delineate directly the relation between the primary lesion and adjacent organs has been made by adopting new CT-guided selective pneumomediastinography (PMG CT). Twenty-three cases were studied with CT guided paravertebral route. Mediastinal invasion on PMG CT was judged by a condition of the air distribution to the adjacent organs. Assessment was made by the use of the findings whether the organs are separated by aeration or not and of presence or not of the "sulcus formation". The accuracy of judging mediastinal invasion has been improved from 41% by conventional CT to 85% by PMG CT based on the diagnostic criteria which adopted "sulcus formation". This method is useful clinically as a testing technique supplementing the conventional diagnostic imaging. PMID- 1448339 TI - [Scandinavia and the WMA (World Medical Association)]. PMID- 1448340 TI - [Prevention and treatment of traveler's diarrhea]. AB - Travelers' diarrhea (TD) affects 20-50 per cent of individuals going to developing countries in Asia, Africa, or Latin America. The etiology varies but is dominated by enterotoxigenic E. coli, found in 30-50 per cent. TD is usually a mild disease, self-limiting in 3-4 days, but 10 per cent of those afflicted have symptoms for one week or more. Prophylaxis of TD involves dietary restrictions and, in selected medical risk groups, antimicrobial drugs. The most important treatment of TD is oral rehydration and loperamide in mild to moderate, non invasive illness. Antibiotics for self-treatment shall be restricted for medical risk groups and individuals travelling far from medical service. PMID- 1448341 TI - [Prokinetic drugs]. AB - Prokinetic drugs--preparations that stimulate gastro-intestinal motility- constitute a relatively new concept in medical therapy, chiefly represented by the products cisapride and metoclopramide. This review consists in an account of the physiological regulation of motility in the upper gastro-intestinal tract where prokinetic drugs are considered to exert their most significant effect, and the therapeutic effects demonstrable in treatment with these drugs. PMID- 1448342 TI - [Bacterial adhesion to epithelial cells of the nasopharynx essential in the development of otitis media]. AB - Otitis media develops when certain bacterial pathogens gain access to the middle ear cavity from the nasopharynx through the eustachian tube. Adhesion of bacteria, in particular Streptococcus pneumoniae and Haemophilus influenzae, to the non-ciliated epithelial cells of the nasopharynx, close to the opening of the eustachian tube, is significantly correlated to the otitis-prone condition in children. Otitis-prone children have significantly fewer bacteria in the nasopharynx coated with the immunoglobulin secretory IgA (SigA) then healthy children have. Adhesion and occurrence of middle ear pathogens in the nasopharynx decreases with advancing age. Epstein-Barr virus, causative agent of infectious mononucleosis, causes a remarkable increase in bacterial adhesion to epithelial cells. PMID- 1448343 TI - [Psychosocial consequences of screening programs in children]. AB - Owing to improved possibilities of early diagnosis, there has been increasing interest in screening children, particularly newborns. However, in the event of false-positive results or certain hereditary risk factors there is a danger of adverse psychosocial consequences, especially negative stigmatization (both of children and their families). Accordingly, except where neonatal screening may be essential for medical reasons, such screening programmes should preferably be scheduled for a later stage in life when the parents are less prone to anxiety about anything that might be interpreted as a threat to the well-being of their offspring. PMID- 1448344 TI - [Problems of drug resistance in developing countries--use and abuse of anti infective agents]. AB - Widespread use and misuse of anti-infective agents have resulted in a problem of drug resistance linked to treatment of infectious diseases. In developing countries especially, the sale of such drugs is poorly controlled and the pharmaceutical industry is dumping obsolete products. Intensive marketing, lack of diagnostic facilities and receptive local cultural attitudes to new "wonder drugs" such as antibiotics, have resulted in dramatic unnecessary use of such. Therefore the ideal strategies for treatment of infectious diseases guided by microbiological diagnosis and resistance pattern are violated in most developing countries, leading to excessive use of anti-infective agents and development of resistance. This has serious consequences for the infections that cause most cases of infant mortality, namely malaria, diarrhoeas and infections of the respiratory tract. Improvements in this vicious circle of drug use and resistance can only be made by attacking several factors simultaneously. There is a need for general information, stricter legislation, essential drug lists, national drug policies, better knowledge of local resistance patterns, better diagnostic facilities, better knowledge about local beliefs about drugs and better communication to local health workers and the community. PMID- 1448345 TI - [Medicine in developing countries--the pathology of poverty. Interview by Eva Oldinger]. PMID- 1448346 TI - [First Scandinavian Gaucher meeting. Treatment with enzyme substitution provides optimism for the future]. PMID- 1448347 TI - [Confidence intervals]. PMID- 1448348 TI - Family medicine education in Canada. AB - Within the sphere of health and welfare, Canada has more in common with the Scandinavian countries than with the United States. This article describes and discusses the unique role of the College of Family Physicians of Canada and the education and training for family medicine, both on the undergraduate and postgraduate levels in Canada. The development of the Master of Clinical Science in Family Medicine degree programme at the University of Western Ontario is considered to be an important vehicle for strengthening academic family medicine in Canada. The amalgamation of current knowledge not only from clinical sciences and educational research, but also from the social sciences, is seen as fundamental to the continued improvement of this discipline. PMID- 1448349 TI - Molecular abnormalities responsible for thrombosis. Genetic aspects. AB - The association between congenital deficiencies and recurrent thrombosis strongly suggests that antithrombin III, protein C and protein S play a major role in inhibiting thrombin formation in vivo. Genetic analysis using DNA fragment amplification by polymerase chain reaction and direct gene sequencing has led to the identification of many novel mutations in qualitative and quantitative deficiencies. Elucidation of the molecular basis of these deficiencies is critical to our understanding of natural antithrombotic mechanisms. It not only provides information on the structural features governing protein function, but also permits a better classification, based on genomic abnormalities of hereditary deficiencies responsible for mild to severe phenotypes and may prove of further value to define the most pertinent plasma assays for routine diagnosis. PMID- 1448350 TI - Air filtration and prevention of aspergillary pneumopathies. Preliminary comparative study of two mobile units for bacteriological air purification with recycling. AB - Two mobile units for air filtration with recycling designed to reduce the aerobiocontamination of hospital rooms were tested. Their efficacity was evaluated by measurement of particle retention and by quantitative determination of the reduction of aerobiocontamination in rooms occupied by patients. Results show a significant improvement in the aerobiocontamination of test rooms as compared to control rooms. It is thus reasonable to suppose that these systems may provide a practical solution to the problems posed by hospitalization in ordinary rooms of patients subjected to aplasive chemotherapy. A randomized clinical trial is in progress. PMID- 1448351 TI - Evaluation of a new haematology analyser for whole blood count and full differential (NE-8000). AB - We evaluated the fully automated haematology analyser TOA Sysmex NE-8000 over a three-month period according to the ICSH protocol using as reference techniques a Coulter STKR counter and microscope examination for WBC differential and cell morphology. The NE-8000 employs aperture impedance to perform cell counts, with a sheath fluid to focus cells hydrodynamically prior to counting and sizing. WBC are differentiated into five populations. A combination of aperture impedance, radio frequency measurement and differential cell shrinkage is used, eosinophil and basophil percentages being established in two separate channels and subtracted from the total granulocyte count in order to give the value for neutrophils. Analysis of 1060 samples processed by the closed sampling automode demonstrated satisfactory counting performance. Among the WBC differentials obtained from 100 samples, neutrophil, eosinophil and lymphocyte results correlated well with those from microscopic examination of blood smears performed according to the NCCLS standard H20 T protocol. Differences observed in the percentages of basophils were of no biomedical significance. A comparative study for monocytes showed poor correlation for values below 5% and above 10%, best results being obtained in the intermediate range 5-10%. The NE-8000 also demonstrated good reliability for detection of abnormal cells. PMID- 1448352 TI - Use of the new Coulter MAXM for leucocyte differentials. AB - The Coulter MAXM is an automated instrument designed to give a complete haematological profile including cell counts and WBC differential (DIFF). The WBC DIFF is determined by tridimensional flow cytometry on the basis of cell volume, light scattering and conductivity (VCS technology). Evaluation of the MAXM DIFF was performed by comparison with microscopic examination of blood smear. A total of 467 samples were studied by the MAXM and reference techniques, according to a standard protocol employed in our laboratory to define the criteria for smear examination. Good correlation was obtained between the two methods in non-flagged samples and those flagged only with an isolated "Imm Gran" message. In a group of 407 non-haematological and 60 haematological patients, there were 12 (2.6%) false positive and 5 (1.1%) false negative reports, all in non-haematological cases and the five false negative results corresponding to no more than minor abnormalities. The Coulter MAXM was thus shown to be an excellent haematology analyser. This instrument was capable of detecting significant abnormalities of blood smears with a sensitivity of 97.9%, a specificity of 94.7% and a global efficiency of 96.3% in the samples examined in the present study. PMID- 1448353 TI - Cell proliferation: analysis by flow cytometry. AB - Cell proliferation can be efficiently analyzed by multiparameter flow cytometry. Different strategies may be used: As a primary approach, static analysis reveals the momentary distribution in a single sample between cell cycle phases, metabolic states, or differentiation lineages. Kinetic analysis uses sequential measurements of cell cycle traverse in synchronized cell populations or accumulation of cells blocked in a particular cell cycle phase. DNA replication analysis is based on the incorporation of the thymidine analogue bromodeoxyuridine. Cell production by mitosis as well as cell loss by cell death can be estimated. Cell production may be assessed by measurement of mitotic rate or S-phase influx. Cycling/non-cycling status may be indicated by proliferation associated antigens. Specific cell clones in experimentally mixed populations can be discriminated using reporter genes. Flow cytometric multiparameter analysis has the potential of revealing and quantitating the heterogeneity with respect to stemlines, proliferation and differentiation. This is of increasing importance in the study of human cancers, as a possible basis for therapeutic decision making. PMID- 1448354 TI - Bone marrow enrichment technique for detection and characterization of scarce abnormal cells. AB - A frequent problem encountered in analysis of bone marrow aspirates is the small number of suspect cells in the material. We present a method for concentration of the cells in bone marrow aspirates which yields smears suitable for immunocytochemical techniques. Bone marrow sampling is performed in two steps: a first aspirate is used to prepare conventional smears and a second aspirate is submitted to two-step centrifugation to separate and collect the nucleated cells without use of a separation medium. Sufficient material is obtained to prepare a large number of films, thus allowing immunocytochemical investigation with a wide panel of monoclonal antibodies. The proportions of the different cell types are similar to those observed in conventional smears and cell morphology is unaltered. This enrichment procedure improves the accuracy of routine cytological bone marrow examination, may be easily applied in laboratories performing bone marrow studies and in our hands has proved of value for the detection and characterization of both malignant blood diseases and bone marrow dissemination of carcinoma. PMID- 1448355 TI - Ethionine: a new antileukaemic drug? AB - In our hands, benzene proved to be a valuable drug for the treatment of chronic leukaemia. When correctly administered it did not provoke the harmful side effects reported by several authors in accord with the first description of von Koranyi in 1912. In many cases benzene induced complete remission persisting for over 18 months. This compound was found to be active even in patients who had not responded to busulphan, although the contrary was also observed for certain subjects. In accordance with previous investigations carried out in the rabbit, concomitant administration of cysteine-HCl blocked the leucopenic effect of benzene in 5 of 6 cases whereas ethionine, an antimetabolite of methionine and/or cysteine, appeared to enhance its therapeutic action. It is worthy of note that in at least one case ethionine administered alone led to complete clinical and haematological remission of the leukaemic state. PMID- 1448356 TI - Clostridium perfringens septicemia during the course of leukemia. AB - Clostridium perfringens (CP) is an infrequent cause of septicemia in neutropenic patients. We report the case of a 17 year old man treated for acute lymphoblastic leukaemia in whom a strain of CP was isolated from blood cultures. The clinical spectrum and evolution of CP septicemia in neutropenic patients are discussed. PMID- 1448357 TI - Relapse as acute monocytic leukaemia of acute lymphoblastic leukaemia with t(4;11). AB - A young adult suffering from acute lymphoblastic leukaemia with t(4;11) relapsed with features of monocytic leukaemia. This unusual evolution is discussed in relation with the pluripotent nature of t(4;11) leukaemic cells. PMID- 1448358 TI - Breast cancer. AB - Breast cancer will continue to be a major health problem for women as long as there is a lack of prevention strategies and underuse of early detection programs. The role of the nurse in health promotion must focus on educating women about the ambiguity surrounding risk factors and the importance of participating in early detection practices. PMID- 1448359 TI - Ovarian cancer. The most lethal gynecologic malignancy. AB - The need for the early detection of ovarian cancer continues to be one of the most important issues in women's health care. The overall 5-year survival rate for epithelial ovarian cancer remains approximately 30% and has not improved over the last three decades. The failure to improve the prognosis for women with ovarian cancer is directly attributable to the lack of an effective screening test for early-stage disease. It is hoped that with the study of those women at high risk, an appropriate screening method will be discovered. Nurses should become knowledgeable about the nature of ovarian cancer, should be able to identify the woman at familial risk, and should look at a symptomatic woman with a high degree of suspicion. As health educators, nurses can provide up-to-date information about Ca 125 serum tests and vaginal ultrasonography used to screen high-risk populations. Nurses must educate women about the importance of the pelvic examination. Historically, nurses are trained to view the patient holistically. Such a viewpoint will help to put together all of the pieces of a difficult puzzle. PMID- 1448360 TI - Holistic care of the patient with cervical cancer. AB - Participation by women in screening programs for cervical cancer is far from optimal, and many lives are lost because of this. Cervical cancer is common, and is easily detected and treated. It has a good prognosis for cure if detected early in its course. Effective screening has been shown to have a major role in decreasing the morbidity and mortality associated with cervical cancer. Therefore, there is a need for increased public health education and availability of screening programs for women. It is particularly important that public health efforts reach women in the lower socioeconomic groups who are less apt to exhibit health promotive behaviors. Women of Latin American heritage are at particularly high risk because of cultural barriers to the discussion of sexual practices. Until public health interventions are more successful, cervical cancer will continue to pose a major threat to women who are either too embarrassed or too misinformed to understand that prevention is an integral part of women's health care. Nurses view patients in a holistic way. It is this philosophy of care that offers women who are diagnosed with cervical cancer a means to adapt successfully to the psychologic and physiologic stresses associated with the diagnosis. Nurses need to recognize this strength and to offer holistic approaches to women in crisis. No two patients deal with a diagnosis of cancer in the same manner. A major challenge to nurses across a hospital community continuum is to provide comprehensive psychologic and physiologic assessment of a women's response to a diagnosis of cervical cancer and to provide effective and holistic intervention when necessary. PMID- 1448361 TI - Lung cancer in women. Rising epidemic, preventable disease. AB - Lung cancer is a preventable disease. Like acquired immunodeficiency syndrome, lung cancer is reaching epidemic proportions in women. This article overviews selected epidemiology of lung cancer and discusses public health issues that are gender-specific to women. Community nursing approaches are advocated that address risk behaviors in women and girls. PMID- 1448362 TI - Domestic violence. The pregnant battered women. AB - Nurses need to understand the theoretic debates that attempt to explain why men batter women. Nurses can participate more effectively in preventing and reducing the incidence of physical violence directed against women in intimate relationships. A raised feminist consciousness will expand the nurse's repertoire of interventions to assist in the identification and treatment of victims. PMID- 1448363 TI - Homeless women. The context of an urban shelter. AB - The role of the nurse in a shelter has just begun to emerge. The prevalence of homeless women is escalating, and nurses are playing primary roles in teaching, health care, social support, and case finding for women in shelters. This article describes some of the health, social, and psychologic issues facing women in a large urban shelter from the perspective of a senior nurse psychologist at Boston's Long Island Shelter. PMID- 1448364 TI - Addicted women. Profiles from the inner city. AB - This article has focused on addicted women and the contexts in which they present to the community nurse. An effort has been made to broaden the clinical applications to include the societal problems underlying addiction and the policy issues that must be addressed to solve them. Addicted women can be described from a societal dimension, in which the health care system reflects disarray and fiscal chaos, and from a community dimension. The two dimensions link the public and the private spheres. To evaluate addicted women and the options for their recovery more effectively, it is helpful to integrate the societal and personal milieu--public issues and the private lives that illustrate them. This is how policy is best formulated. The numbers of addicted women in the health care system reflect only the tip of the iceberg. Health care providers must strive to reach women who are outside of the health care system who have not been connected to a hospital, shelter, or home care agency. Researchers need to differentiate sample patient populations, and the patient selection bias needs to be addressed early on. A model of a community support for recovery located within a housing project was a viable option for reaching addicted women. The role of nurses is becoming increasingly unique. Nurses are skilled as caregivers and clinicians. They can open doors of opportunity for inner-city women and children by developing health-promotive programs in hospital settings for substance abusing women and by continuing to work with their colleagues in the community context. On both dimensions, nurses have front-line accessibility to women and children who are vulnerable. Often, commonality of gender strengthens the nurse/patient relationship and facilitates trust as well as empathy between female addicts and their nurse advocate counterparts. Never has the call to inner-city nurses been more compelling. The problems related to drug abuse and parenting are multidimensional. They resist easy definition and solution. Nurses have the education and the clinical expertise to provide front-line interventions for inner-city women who are addicted to drugs. Nurses are educated holistically as caregivers and teachers. Ideally, nurses can exert their strongest impact on health promotion in the neighborhoods of communities. In reality, this has not worked, and nurses remain part of a health care system that has failed inner-city poor women and their children. Nurses in hospitals and in community setting spend most of their time applying "bandages" to the psychologic and physical wounds that emerge from the addiction to drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1448365 TI - Identifying the woman with alcohol problems. The nurse's role as gatekeeper. AB - Alcoholism among women, although frequently undetected, is on the rise, posing a significant social health problem. Nurses acting as gatekeepers are in an excellent position to identify alcohol problems and refer the individual to the appropriate health care provider. Concern about a lack of knowledge of signs of this problem and ingrained moralistic attitudes often interfere with this process. This article reviews some of the historical antecedents contributing to our present view of alcoholism, explores some of the known differences between male and female alcoholics, defines the tasks and limits of the nurse's role as gatekeeper, and identifies helpful qualities of the nurse. PMID- 1448366 TI - HIV infection in women. Implications for nursing practice. AB - Much remains to be explained regarding women with HIV infection or AIDS. Interest in determining whether the natural history of the disease or the clinical manifestations are gender specific is leading to more research focused on women. The female roles of childbearer and caretaker evoke ethical issues that are unique to this epidemic and that can impact on the development and delivery of health care services. Women at the greatest risk for HIV disease are not likely to form coalitions to advocate for services, research dollars, and education. They need advocates and assistance in becoming united to advocate for themselves. Nurses have a critical role in the provision of services to women with HIV disease. As educators, direct service providers, and administrators, nurses contribute to the development of services that are holistic and family centered. As advocates, nurses can ensure that women are accurately and well informed about the disease and the resources available to them. Because AIDS no longer affects only those persons living in large metropolitan areas, it is imperative that all nurses become experts in the care of women with AIDS and advocates for a better outcome. PMID- 1448367 TI - Older women. Sexually transmitted diseases and acquired immunodeficiency syndrome. AB - Increasingly, American women aged 50 and over are afflicted with sexually transmitted diseases (STDs) and acquired immunodeficiency syndrome (AIDS). In order to meet the US Public Health Services' Health Objective for the Year 2000, health care workers must address the issues that impact on the older woman's ability to protect herself and others from these highly stigmatized diseases. Nurses must be aware of the potential for STDs and AIDS in this population and appropriately refer individuals for screening and follow-up care. Older women must be empowered economically, legally, and politically so they can assume an assertive role in their own health promotion. Cultural and societal barriers need to be overcome to change stereotypic attitudes about older women's sexuality. Only then can access to health information, health care, and research be assured. PMID- 1448368 TI - Women at midlife. The transition to menopause. AB - The advantage over men that women experience in life expectancy does not extend to morbidity. Although women live on average approximately 7 years longer than men, their later years are often filled with medical problems. Much is currently known that could influence and effect improved health for women. Menopause is not a dramatic event that signals an abrupt change in the health and well-being of women. Rather, it is a transitional time of perhaps a 25-year span when estrogen production gradually declines and results in a variety of bodily changes. Concurrent with the hormone changes are other effects of the normal cycle of aging. Comprehensive multidisciplinary health care clinics for adult women have the potential to provide health services that women seek. PMID- 1448369 TI - Women at midlife. Hormone replacement therapy. AB - As women approach the climacteric period, many changes are occurring in their bodies. Many of the physiologic changes are related to a decrease in estrogen production by ovaries. Hormone replacement therapy has been proposed to help relieve many of the manifestations associated with menopause. Before they begin hormone replacement therapy, women need to be informed about the advantages and disadvantages of this treatment. Decreasing the risk of cardiovascular disease and preventing further development of osteoporosis are primary reasons for administering hormone supplementation to postmenopausal women. The risk of breast cancer is not increased with low-dose estrogen, and by adding progesterone, the risk of endometrial cancer is virtually eliminated. Not every woman is a potential candidate for hormone replacement therapy. Contraindications exist, and some women experience discomforting side effects. Withdrawal bleeding with combination therapy is the main reason women do not comply with treatment protocols. Although supplementation may prove helpful for the postmenopausal woman, each individual needs to evaluate her own personal situation carefully. Accurate knowledge about normal changes due to decreased estrogen production, the pros and cons of therapy, and personal health status assists in the decision as to whether hormone replacement therapy is appropriate for a particular postmenopausal woman. PMID- 1448370 TI - Nutrition in women across the life span. AB - Recent recommendations on nutrition, such as the Surgeon General's Report on Nutrition and Health, have emphasized the relationship between diet and disease. In the Surgeon General's report, Americans have been advised to limit their consumption of fat, cholesterol, sodium, and alcoholic beverages, and to increase their consumption of complex carbohydrates and fiber. Two of the recommendations in this report related to the consumption of iron and calcium are particularly important to women's health. Women are advised to increase their consumption of food high in calcium and to include foods containing iron, such as lean meats, fish, certain beans, iron-enriched cereals, and whole grain products. Iron is essential as a constituent of hemoglobin, myoglobin, and certain enzymes. Iron losses during menstruation and the increased need for iron during pregnancy place women at risk for iron deficiency. Bone mass continues to increase until the late twenties, and one method to prevent osteoporosis may be adequate calcium intake during these years of early adulthood. Food guides that list amounts and types of foods to be eaten are helpful for the individual or as an educational tool for the nurse or educator. A Daily Food Guide was recently designed to meet the nutritional needs of women throughout the life cycle, and the government has very recently released a Food Guide Pyramid. Although it is important for women to learn how to control certain dietary components, they should also be aware of the protective nature of certain nutrients, such as iron and calcium. PMID- 1448371 TI - Predictors of depression in women. AB - The identification of depression in women is a challenge for nurses. Case finding for health promotion can be performed when risk factors are identified, when a determination of symptoms using DSM III-R2 criteria is made, and when the clients are referred for appropriate interventions. The referring nurse can be a support system while the client is in the initial phases of intervention. Nurses can have a major role in the identification of and planning of treatment for women who are depressed or at risk for depression. PMID- 1448372 TI - Using Kryofix as alternative for formalin results in more optimal and standardized immunostaining of paraffin sections. AB - Although used for over one century formalin has several disadvantages which Kryofix, an alternative fixative for paraffin blocks used in Leiden for 6 years, does not have. In this study the effects of Kryofix on tissue regarding immunohistochemistry are compared with those of buffered formalin. All markers studied showed enhanced staining in the Kryofix blocks after 4 hours of fixation, whilst in some cases the immunostaining of the formalin blocks was even negative. For all markers, the sera could be further diluted for the Kryofix sections, for some with as much as a factor 20, enhancing the cost-effectiveness of the method. We established that for formalin, the fixation time strongly influenced the results. For Kryofix there was no time factor: the immunostaining results of 1 hour fixation were identical to those after 3 months of fixation. This study shows that by this method of fixation, in which there is no cross-linking of proteins, immunostaining of paraffin sections is optimized and standardized. PMID- 1448373 TI - Tumour-like lesions of the salivary glands. The new WHO classification. AB - Tumour-like lesions must be distinguished from true tumours of the salivary glands. In the new WHO classification of salivary gland tumours seven entities were considered: sialadenosis, oncocytosis (diffuse oncocytosis and focal adenomatous oncocytic hyperplasia), necrotizing sialometaplasia (salivary gland infarction), benign lymphoepithelial lesion (chronic myoepithelial sialadenitis), salivary duct cysts (mucoceles of the minor salivary glands of extravasation or retention type, cysts of the major salivary glands, ranula and dysgenetic polycystic disease of the parotid gland), chronic sclerosing sialadenitis of the submandibular gland (Kuttner tumour), and cystic lymphoid hyperplasia in AIDS. The main topics of clinical data and pathohistology were described and documented by the results of the Salivary Gland Register in Hamburg (1965-1989). PMID- 1448374 TI - Morphometric distinction of sclerosing adenosis from tubular carcinoma of the breast. AB - Objective features have been identified that assist in distinguishing sclerosing adenosis from tubular carcinoma of the breast. Hematoxylin and eosin stained paraffin sections of 18 sclerosing adenoses and 18 tubular carcinomas were studied using a TAS Plus image analysis system. Histological measurements from lumens and glands included stereologic features of architecture and morphometry of size and shape (the latter by Fourier coefficients). Cytological measurements included nuclear area, perimeter, diameter and formfactor. Initial analysis suggested utility for several individual features. However, after a modified Bonferroni procedure only two of the features were statistically significant, i.e. the coefficient of variation of luminal form factor and the surface density of glands. Multivariate discriminant analysis using these two variables correctly classified 86% of the cases, with three adenoses and two carcinomas misclassified. Validity of the discriminant rules was supported by classification using measurements from a separate, independent set of cases (ten sclerosing adenoses and nine tubular carcinomas). The classification function computed from the first set misclassified only one case from the second set, a tubular carcinoma, leaving 95% of the cases successfully categorized. Chi square test for 2 x 2 contingency tables gave a p-value < 0.001 for both sets of cases. The results suggest that morphometric features are helpful in distinguishing tubular carcinoma from sclerosing adenosis and point out the need for conservative analysis of high-dimensional data sets. PMID- 1448376 TI - Assessment of the risk on endometrial cancer in hyperplasia, by means of morphological and morphometrical features. AB - The value of two "cancer risk" assessment rules (one consisting of qualitative microscopical features and one consisting of morphometric characteristics) has been evaluated in 39 patients with hyperplasia of the endometrium. Of these, in seven (7139 = 18%) cancer was detected in the follow-up and 32 remained stable or became less abnormal. The results of the qualitative analysis were well in agreement with those published earlier. In none of the eight patients with simple hyperplasia cancer was detected, in contrast to five of the 11 patients (45%) with cytologic atypia and glandular complexity. Twenty patients showed cytologic atypicality in the absence of glandular complexity, or no atypicality but glandular complexity; in two (10%) of these patients cancer was detected later in the follow-up. The morphometric rule (consisting of volume percentage of stroma, log-normally transformed standard deviation of the shortest nuclear axis and outer surface density of the glands) results in a multivariate score. Nineteen patients had a score value above 0.6 and in none of them cancer was found. In contrast, in seven of the 20 patients (35%) with a score value below 0.6, cancer was detected. Regarding the question which of the techniques is more powerful, the specificity is better with the qualitative evaluations; the sensitivity is higher with the morphometric rule. An advantage of the morphometric rule is that only two groups (very low/very high risk) are discerned. PMID- 1448375 TI - Nucleolar silver staining patterns and HLA-DR antigen expression in bronchial epithelial cells in chronic bronchitis. AB - Bronchial epithelial cells obtained by brush biopsy during fiberoptic bronchoscopy performed in 12 patients with chronic bronchitis and 12 healthy control subjects, were investigated for HLA-DR antigen expression and nucleolar silver staining patterns. In all patients with chronic bronchitis the number of bronchial epithelial cells positive to HLA-DR antigen was highly increased (> 90%), whereas in the controls only a few epithelial cells (< 10%) showed a weak HLA-DR antigen expression. Patients with chronic bronchitis showed an increased lymphocytic reaction compared to the control subjects. Both in the patients with chronic bronchitis and in the healthy controls the number of nucleoli was the same. The number of silver stained dots per nucleus was significantly higher in patients with chronic bronchitis than in the control subjects (7.70 +/- 0.87 as against 5.11 +/- 0.52; p < 0.0001). The intensity of the lymphocytic reaction correlated with the HLA-DR antigen expression and the increase in silver staining (Spearman's r = 0.543; p < 0.01). This indicates the influence of inflammation on the activation of epithelial cells derived from the respiratory tract. PMID- 1448377 TI - Morphometric discrimination of colonic tubular adenoma from adenocarcinoma by vector and tensor analyses. AB - Four parameters were considered in this study to discriminate between tubular adenoma and adenocarcinoma of the colon. The deformation of the tubular profile (TD) and the average sector resultant (AR) were used as supracellular parameters, the vector resultant strain (VS) which represented the cellular crowding as a cellular parameter, and the deformation of the nucleus (ND) as a nuclear parameter. Statistical comparison between the two groups showed that all the parameters had high levels of significance. Direct discriminant analysis was applied to discriminate between the two diseases and all parameters showed large F-ratios; however, the evaluation by the stepwise discriminant method indicated that ND had a sufficient power of discrimination between the two diseases. Biplot with confidence interval ellipses (95%) was plotted for ND versus TD to demonstrate the graphical separation of the groups. PMID- 1448378 TI - Differentiation of human thyroid follicle cells from normal subjects and Basedow's disease in three-dimensional collagen gel culture. AB - Thyroid follicles, an essential functional unit of the thyroid, exist in the extracellular matrix of the tissue in vivo. Therefore, in any monolayer culture system, the follicles cannot be reconstructed. Our previous study adopting three dimensional collagen gel culture showed that isolated porcine follicle cells reconstructed thyroid follicles specific for the thyroid gland in vivo. To elucidate whether this culture system is also applicable to human follicle cells, and furthermore to provide a culture system for investigations of the pathogenesis of human thyroid diseases, we tried to culture isolated human follicle cells of normal thyroid tissue and of Basedow's disease in three dimensional collagen gel. In this culture system, they apparently reconstructed thyroid follicles. The component cells of the reconstructed follicles exhibited structural polarity specific for human thyroid follicle cells and produced thyroid hormones. In addition, the cells responded to a TSH-stimulation in terms of morphological and functional differentiation, and they presented HLA-DR antigen with an interferon-gamma-stimulation. This report is a first instance of reconstruction of human thyroid follicles and HLA-DR antigen induction in three dimensional follicle structures in vitro. This culture system provides a more physiological environment in vitro for biological and pathogenetic investigations of human thyroid follicle cells than the monolayer culture system. Further experiments using this method will probably provide new clues to the pathogenetic mechanisms of human thyroid diseases. PMID- 1448379 TI - Small adrenocortical tumors without apparent clinical endocrine abnormalities. Immunolocalization of steroidogenic enzymes. AB - Immunohistochemical analysis of steroidogenic enzymes (P-450 side-chain cleavage, 3 beta-hydroxysteroid dehydrogenase, P-450 C21-hydroxylase, P-450 17 alpha hydroxylase and P-450 11 beta-hydroxylase) was performed on fifteen cases of small adrenocortical adenomas, which were detected incidentally in hormonally asymptomatic patients (non-functioning adrenocortical tumor), in order to study steroidogenesis in these tumors. Immunolocalization revealed that all cases examined expressed all the enzymes in the adrenocortical steroidogenic pathway to various degrees, and in twelve cases abnormalities of precursor hormones and steroid metabolites were clinically observed. Attached non-neoplastic adrenals were present in twelve cases. Among these twelve cases, eight showed cortical atrophy, especially in the zona fasciculata. These atrophied adrenals expressed little immunoreactivity of the enzymes examined. These results strongly indicate that most of small non-functioning adrenocortical tumors have the capacity to produce biologically active steroids including cortisol, although not necessarily associated with hypercorticism. Especially in the cases with cortical atrophy in attached non-neoplastic adrenals, it is considered that autonomous neoplastic production and secretion of cortisol may be insufficient to cause clinical and routine laboratory abnormalities but sufficient to subtly alter the hypothalamic pituitary-adrenal axis by suppressing ACTH and/or CRF secretion and to result in adrenocortical atrophy. It should be recognized that corticosteroidogenesis does take place in the majority of clinically small non-functioning adrenocortical tumors incidentally detected in hormonally asymptomatic patients when managing these patients. PMID- 1448380 TI - Meningothelial meningioma with "amianthoid" fibers. Case report with ultrastructural study. AB - The case of a meningothelial meningioma with 'amianthoid' fibers in a 48-year-old woman is presented. By light microscopy the tumor showed the typical features of meningothelial meningioma and rounded, deeply eosinophilic, and fibrillary areas, especially around and/or in the vicinity of blood vessels. These fibers are also called 'amianthoid' fibers. Ultrastructurally, these foci were made up of disorderly arranged and interwaving mature collagen fibrils with a variable width between 40 and 190 nm. No evidence of intracellular collagen synthesis by the tumor cells was found. The presence of 'amianthoid' fibers does not seem to carry any prognostic significance. PMID- 1448381 TI - Cell-matrix patterns in the cutaneous lesion of chromomycosis. AB - Chromomycosis is a chronic fungal infection characterized by dermal fibrosis with persisting fungi in situ, generally leading to a verrucous skin lesion. The absence of good clinical results under specific treatment suggests irreversibility of the fibrotic lesion. Frozen and paraffin-embedded skin biopsies of eleven patients with chromomycosis due to Phialophora pedrosoi were studied by immunohistochemistry and electron microscopy. Distinct cell-matrix patterns were found in different tissue localizations: neutrophilic abscesses with oedema and necrotic keratinocytes in the epidermis; dense connective matrix around inflammatory infiltrates, mainly composed of macrophages and giant cells, and organized granuloma in the dermis. Active fibroblasts and mast cells were constantly observed. The inability of fibrotic tissue to be remodelled seems correlated to the nature and the organization of the matrix components but, the factors triggering the initial fibrogenic events remain to be characterized. PMID- 1448382 TI - The long-term prognosis of the primary glomerulonephritides. A morphological and clinical analysis of 1747 cases. AB - Long-term studies of all types of primary glomerulonephritis (GN) taking into consideration the major morphological and clinical findings revealed the following: 1) Endocapillary GN, post-streptococcal type has a very good prognosis when only glomerulitis is present. The prognosis is significantly worse if either interstitial inflammation with fibrosis or nephrotic syndrome (NS) is present at the time of the biopsy. 2) The prognosis of the various types of mesangioproliferative GN (IgA nephritis, non-IgA nephritis, and immunohistologically negative GN) is very good if there is only glomerulitis. The prognosis is worse for all three types when the renal cortical interstitium exhibits inflammation with fibrosis at the time of the biopsy, and is worst of all when both interstitial fibrosis (IF) and the signs of acute renal failure (ARF) are present. Of this group, the type in which there are negative immunohistological findings exhibits the best prognosis. No difference in prognosis is found between IgA nephritis and non-IgA nephritis. 3) Minimal changes GN with NS has a very good prognosis when the interstitium is not involved. The presence of interstitial inflammation and fibrosis worsens the prognosis significantly. 4) Focal sclerosing GN has a much poorer prognosis than minimal changes GN with NS, even when there is glomerulitis only (5- and 10-year renal survival rates (RSRs) of 90% and 67%, respectively). If interstitial inflammation and fibrosis are present, the prognosis is significantly worse (5- and 10-year RSRs of 84% and 55%, respectively). The prognosis is worst when both ARF and IF are present at the time of the biopsy (5- and 10-year RSRs of 56% and 46%, respectively). From the clinical side, the prognosis is significantly worse if, at the time of the biopsy, NS is present or the serum creatinine concentration is elevated to more than 1.3 mg%. 5) Chronic membranous GN has a better prognosis than focal sclerosing GN if glomerulitis only is present (5-year RSR, 88%; 10-year RSR, 77%). If the renal cortical interstitium is also involved (in the form of IF), the prognosis is significantly worse (5-year RSR, 65%; 10 year RSR, 38%). The prognosis in this disease, too, is worst when both ARF and IF are present at the time of the biopsy (5-year RSR, 38%; 10-year RSR, 25%). 6) Membranoproliferative GN has a worse prognosis than any of the types of GN so far mentioned (5-year RSR, 51%; 10-year RSR, 32%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1448383 TI - Cellular autofluorescent pigment and interstitial fibrosis in smoker's lung. AB - The mechanisms by which cigarette smoking lead to bronchopulmonary diseases are incompletely understood. The most characteristic lesion is a chronic macrophage alveolitis accompanied by slight fibrosis and emphysema. The macrophages contain a ceroid-like granular autofluorescent pigment in their lysosomes. Using immunohistochemical methods, open lung-, transbronchial biopsies and cells obtained by broncho-alveolar lavage from cigarette smokers were studied: anti human macrophage serum and anti-human elastase, immune sera against type I, type III collagens and fibronectin were used in the demonstration of the cellular components of alveolitis and the connective tissue constituents of fibrosis. The characteristic red-brown autofluorescent pigment of the macrophages was also found in an extra-alveolar location mainly in peribronchial, septal and pleural scars. Similar emission colour occurred focally in the elastic laminae of fibrotic alveoli and sclerotic arteries. Granular fluorescent pigment was found in many bronchial epithelial cells. The epithelial pigmentation was associated with increased transcription of nucleic acid proteins, revealed by colloid silver (AgNOR) reaction. The results suggest that the autofluorescent pigment substances in macrophages may indicate or also play a role in the development of pathological connective tissue and epithelial changes of smoker's lung, in addition to the known mediators and enzymes. PMID- 1448384 TI - Mobilization of iron and iron-related proteins in rat spleen after intravenous injection of lipopolysaccharides (LPS). AB - We used lipopolysaccharide (LPS) to provoke immune responses and observed the changes in the localization of iron and iron-related proteins, such as transferrin receptor, ferritin and hemosiderin in the rat spleen. After intravenous injection of 250 micrograms LPS (salmonella minnesota R595), spleen weight and serum IgM levels increased, cells incorporating 5-bromo-2' deoxyuridine (BrdU), and transferrin receptor positive cells increased in the peripheral portion of the periarterial lymphoid sheath (PALS), the marginal zone (MZ) and the follicles. Ferritin positive cells increased markedly in the white pulp and stainable iron increased in the marginal metallophils (MM) and in the macrophages in the MZ and the outer PALS. Even in iron deficient rats, a similar change was observed for the localization of iron and iron-related proteins after injection of LPS. After injection of 0.4 mg keyhole limpet hemocyanin (KLH), changes similar to but less pronounced than that in the LPS injected rats were observed for serum IgM levels and for the localization of iron and iron-related proteins. These results showed that the iron in the MM and the macrophages in the white pulp have a dynamic response to immunological challenges and suggested that they play some role in immune responses. PMID- 1448385 TI - Zinc concentrations in human tissues. Liver zinc in carcinoma and severe liver disease. AB - In 58 unselected necropsies, zinc (Zn) in specimens of liver (mean +/- s = 280 +/ 178 micrograms/g d.w./4.28 +/- 2.72 mumol/g d.w.), kidney (170 +/- 57 micrograms/g d.w./2.60 +/- 0.87 mumol/g d.w.), spleen (69 +/- 13 micrograms/g d.w./1.05 +/- 0.20 mumol/g d.w.), and lung (64 +/- 16 micrograms/g d.w./0.98 +/- 0.24 mumol/g d.w.) were analysed by means of flameless atomic absorption spectrometry. In the examined range from 25 to 92 years of age, the Zn concentrations in all tissues measured did not show age or sex-dependency. There was a high correlation between the tissue concentration of Zn and Mg in lung, liver, and spleen, between Zn, Mg, and Pb in liver as well as between Zn and Pb and Zn and Cd in kidney. All hepatic cirrhosis cases had very low Zn conc. in liver tissue, the tumor cases generally increasing Zn conc. in liver tissue with progressive stage of regional invasion and distant metastasis. PMID- 1448386 TI - Endometrial cancer associated with polycystic ovaries in young women. AB - Two women (17 and 36 years old) are presented, who complained about abnormal vaginal bleeding. The rare diagnosis of an adenocarcinoma of the corpus uteri with concomitant polycystic ovaries (Stein-Leventhal-Syndrome) was made. PMID- 1448387 TI - Patterns of measles pneumonitis. AB - As a result of the enlarging pool of unvaccinated children and young adults, there has been an increase in serious measles pneumonitis in our areas. We recently examined autopsy and/or lung biopsy material from five children with fatal measles pneumonitis. Two patients were immunocompromised because of either prematurity or acute leukemia and died 13-16 days following onset of symptoms. Both had classic giant cell pneumonitis, with readily demonstrable intranuclear inclusions. Three other children without known immunocompromise had a more prolonged course. The lungs of these patients lacked the classic pattern and displayed instead a spectrum of less specific findings ranging from organizing diffuse alveolar damage to interstitial pneumonia with giant cells, but without viral inclusions. An accompanying necrotizing bronchiolitis was also present. Electron microscopy and/or detection of elevated measles-specific immunoglobulin M was necessary to confirm the diagnosis in these apparently immunocompetent patients. We conclude that the histologic features of fatal or serious measles pneumonitis are variable and depend to some extent on the immunocompetence of the host as well as the duration and tempo of the disease. Ancillary studies may be necessary to establish the diagnosis in cases lacking classic histopathologic features. PMID- 1448388 TI - Rectal myopathy in chronically constipated children. AB - We examined full-thickness rectal biopsies from 30 children who had chronic constipation, including 5 children with constipation associated with clinical symptoms of intestinal pseudo-obstruction. Biopsies from 9 patients who required colonic interposition and from 7 with Hirschsprung's disease were used as controls. Tissues were evaluated for muscularis mucosae thickness (in mm), for absolute circular and longitudinal muscle layer thicknesses and their ratio, and for the intensity of neural vasoactive intestinal peptide (VIP) immunohistochemical staining. Atrophy of the rectal musculature with focal muscle fiber vacuolation or muscle fiber disappearance was found in all children with chronic constipation. Muscularis mucosae thickness was increased (P < .01) and the circular-to-longitudinal muscle ratio was decreased in the constipation group, with the greatest degree of atrophy being demonstrated in the circular layer. Two of the patients had additional biopsies up to 9 years after the first that illustrate progressive myopathic changes over time. This study demonstrates muscular atrophy in the rectum of children with chronic constipation. Besides primary idiopathic disease, potential etiologies include chronic distention, denervation, functional obstruction from obstipation, alteration in gut hormones, and toxic, ischemic, or neural injury. PMID- 1448389 TI - Use of fluorescent in situ hybridization to detect trisomy 13 in archival tissues for cytogenetic diagnosis. AB - The present report describes the use of molecular probes to investigate the chromosomal constitution of interphase nuclei of formalin-fixed, paraffin embedded tissue from three infants with multiple congenital malformations and a provisional diagnosis of trisomy 13 in two. Fluorescent in situ hybridization with the probe for the 13 and 21 centromeric regions revealed five nuclear signals in two of the cases, indicating the presence of an extra chromosome, and only four nuclear signals in the other case. Only the two positive cases had phenotypic features consistent with trisomy 13. Routine cytogenetic analysis was performed on one child and confirmed an additional chromosome 13. The child without an extra chromosome had features consistent with Ivemark syndrome. This study demonstrates the utility of fluorescent DNA probes for the retrospective diagnosis of aneuploidies in archival material. PMID- 1448390 TI - Glomic cells and their peptides in the carotid body of the human fetus. AB - Carotid bodies from 15 human fetuses of gestational ages 13-19 weeks were examined by light and electron microscopy. They were also labeled with antisera to methionine- and leucine-enkephalins, substance P, and bombesin. At 13 weeks of gestation most fetal glomic cells formed a homogeneous population but a few could be distinguished by light microscopy as rounded, pale fetal chief cells or elongated, darker fetal sustentacular cells, a distinction that became more certain with increasing gestational age. Electron microscopy confirmed this distinction, in which fetal chief cells contained dense-core vesicles and were partially enfolded by cytoplasmic extensions of fetal sustentacular cells. Immunoreactivity to methionine- and leucine-enkephalins was found at all gestational ages and was confined largely to fetal chief cells. Immunoreactivity to substance P was less specific, and there was no reaction for bombesin. Thus, by as early as the 13th week of gestation the two principal types of cell of the mature human carotid body begin to become recognizable on paraffin-embedded sections stained with hematoxylin and eosin. Furthermore, fetal chief cells can synthesize the peptides found in the adult. PMID- 1448391 TI - Oral congenital cystic choristomas: a case report. AB - Solitary choristomas containing gastrointestinal mucosa occur rarely in the tongue and the oral mucosa and usually present as an asymptomatic mass. This report documents the occurrence of two congenital intraoral cystic choristomas in a 5-month-old male infant. The cysts were located on the dorsum of the base of the tongue and left floor of mouth anterior to the lingual cyst. Both cysts were lined by nonkeratinizing squamous epithelium and gastric, intestinal, and respiratory epithelium. The cysts were excised by an oral approach. PMID- 1448392 TI - Chronic granulomatous disease: an ultrastructural study of the pigment laden histiocytes. AB - We have studied the ultrastructural characteristics of the pigments in the macrophages of liver and lymph nodes from three children with chronic granulomatous disease (CGD). The pigments represent lipofuscin bodies and appear to be formed from lysosomes. Characteristic structures are believed to represent transitional stages between lysosomes and mature pigment granules. It is thought that the residual lipids undergo progressive oxidation secondary to deficient lipolytic activity, overloading the lysosomes. It was also noted that liver biopsy can be a valuable tool in confirming the diagnosis of CGD, particularly when the disease is clinically suspected but the results of the nitroblue tetrazolium test are equivocal. PMID- 1448393 TI - Meconium periorchitis. PMID- 1448394 TI - Congenital lipoblastoma of the hand. PMID- 1448395 TI - Congenital syphilis in a twin gestation. PMID- 1448396 TI - Granulomatous meningoencephalitis due to leptomyxid ameba. PMID- 1448397 TI - Histopathologic variability of finding erythroid inclusions with intrauterine parvovirus B19 infection. PMID- 1448398 TI - An overview of survival studies in patients with heart failure. AB - Heart failure is associated with poor prognosis, but recent large-scale investigations have generated valuable and practical information to help improve clinical management and patient survival. This review presents an overview of the findings of recent heart failure survival studies and how these may affect therapeutic strategy for patients with this condition. PMID- 1448399 TI - The chronic fatigue syndrome. PMID- 1448401 TI - The law and medical fitness to drive--a study of doctors' knowledge. AB - We assessed doctors' knowledge on laws and recommendations regarding fitness to drive in certain medical conditions by a questionnaire survey. A total of 646 doctors consisting of 400 general practitioners and 246 hospital doctors of all grades were circulated with the questionnaire. The survey was anonymous so non responders could not be re-circulated. The response rate was 26% general practitioners and 32% (hospital doctors). The results show the poor knowledge of doctors on several aspects of fitness to drive. It is necessary for all doctors to have a basic knowledge on the laws and recommendations on fitness to drive so that they can advise their patients correctly. Our survey clearly shows that doctors' knowledge is poor. Many drivers may therefore be placing themselves and others at risk. It is mandatory that this subject receives more attention in undergraduate and postgraduate education and that doctors should be regularly updated on new recommendations from the Driver and Vehicle Licensing Agency. PMID- 1448400 TI - The menopause and hormone replacement therapy. PMID- 1448402 TI - Cardiovascular complications of parenteral nutrition. AB - During a 3 year period, 1987-1989, we encountered three major complications associated with parenteral nutrition leading to congestive cardiac failure--acute beriberi, right atrial and superior vena caval thrombosis, and fungal endocarditis. Unrecognized, these are invariably fatal. Persistent vomiting from intestinal obstruction led to the development of thiamine deficiency in the patient with beriberi. Recurrent catheter tip sepsis probably accounted for thrombosis and endocarditis in the second and third cases, respectively. These conditions are preventable with careful attention to nutritional replenishment and aseptic technique. In patients with catheter-related sepsis early, repeated blood culture is of diagnostic value. Patients with Staphylococcus aureus catheter-associated bacteraemia require at least 4 weeks of appropriate antibiotic therapy. Recurrent sepsis, especially when associated with pulmonary embolic phenomena, is an indication for echocardiography. PMID- 1448403 TI - Concentrations of vitamins A, C and E in elderly patients with Parkinson's disease. AB - Concentrations of the naturally occurring antioxidant vitamins A, C and E were measured in 27 patients with Parkinson's disease and 16 age-matched control subjects, from a similarly disabled patient group. There was no significant difference in the serum concentrations of vitamins A and E in the two groups. Vitamin C was significantly higher (P < 0.05) in the Parkinson's disease group, however, the mean leucocyte vitamin C concentration in the control group was low (101 nmol/10(8) WBCS) compared to established data in healthy young individuals (119-301 nmol/10(8) WBCS). There was no correlation between the severity or duration of Parkinson's disease and concentrations of vitamins A, C and E. There is therefore no evidence from this study that a deficiency of these antioxidants contributes to the onset or progress of Parkinson's disease. PMID- 1448404 TI - Microalbuminuria in non-insulin-dependent (type 2) Nigerian diabetics: relation to glycaemic control, blood pressure and retinopathy. AB - Twenty-four hour urinary albumin concentrations were measured in 113 (mean age 51.1 years) non-insulin-dependent (NIDDM) Nigerian diabetics (50 males, 63 females). A high prevalence of microalbuminuria (> or = 30 mg/24 hour) was observed in male (54%) as well as female diabetics (59%). Microalbuminuria was also observed in a high proportion of diabetics (52%) with a short duration (< 5 years) of disease. Elevated blood pressure and retinopathy were present in 41% and 16% of patients respectively. Among the 49 patients with normoalbuminuria (< 30 mg/24 hour), six (12%) had retinopathy compared with 12 (18%) in the microalbuminuria group. Diastolic blood pressure levels were significantly higher (P < 0.01) in male diabetics with retinopathy but this was not associated with higher albuminuria. Urinary albumin concentrations were not influenced by elevated blood pressure. There were no significant differences in age, duration of diabetes, blood pressure or serum creatinine between diabetics with and without microalbuminuria. These results suggest that though there is a high prevalence of microalbuminuria amongst NIDDM Nigerian diabetics it may not predict retinopathy and occurs independently of either glycaemic control or elevated blood pressure levels. PMID- 1448405 TI - Magnetic resonance imaging for the assessment of residual masses after treatment of non-Hodgkin's lymphomas. AB - Eight patients with non-Hodgkin's lymphoma who were in clinical remission but showed residual masses after therapy were examined with magnetic resonance imaging at 1.5 T at the end of therapy, with the sequences TR/TE:500/35,500/70,2000/35 and 2000/70. Residual masses were found in lymphoid areas (7), spleen (3) and kidney (1). In three patients, T2 showed high signal intensity. Disease progressed in the following 1-3 months and active lymphoma was histologically identified. In the other five patients, T2 showed a very low signal intensity. One of them had a distant relapse in lymphoid areas but the remaining four patients are asymptomatic after a mean follow-up time of 13 months, suggesting that the lymphoma is cured and the mass inactive. We conclude that magnetic resonance imaging seems to distinguish active from non-active residual masses after treatment of non-Hodgkin's lymphoma patients otherwise in clinical remission. PMID- 1448406 TI - The value of urinary red cell shape in the diagnosis of glomerular and post glomerular haematuria. A meta-analysis. AB - The proportion of dysmorphic red cells (DRC) in the urinary sediment and their mean corpuscular volume (MCV) have been claimed to discriminate between glomerular and postglomerular sources of haematuria. To determine the diagnostic value of urinary DRC and MCV, we searched the literature and critically reviewed 21 published studies using a predetermined set of criteria for evaluation. All studies originated from referral centres. Interobserver variability in identifying urinary DRC was reported in four studies and found to be unacceptably large in one. Although reproducible over different samples of the same individual, urinary MCV was unreliable in cases of low-grade haematuria because of interfering debris. Weighted averages and 95% confidence limits of the sensitivity and specificity of the DRC proportion for glomerular disease were 0.88 (0.86-0.90) and 0.95 (0.93-0.97), respectively; those of a low MCV were 1.00 (0.98-1.00) for sensitivity and 0.87 (0.80-0.91) for specificity. Sensitivity and specificity values derived from in-patients were slightly higher than those in referred outpatients. No studies of urinary DRC or MCV in patients with incidentally detected microhaematuria in the primary care setting were found. We conclude that at present the diagnostic value of urinary DRC and MCV is limited. In referral centres, that is, in patients with a high probability of postglomerular haematuria, the test cannot rule out urological lesions, because its specificity for glomerular disease may be as low as 0.80. In the primary care setting, that is, in unselected patients with incidentally detected low-grade haematuria, the accuracy of the test has not been studied but may be even lower. The use of urinary DRC or MCV as an indicator of the source of haematuria is in need of further experimental development and confirmation. PMID- 1448407 TI - Costovertebral joint dysfunction: another misdiagnosed cause of atypical chest pain. AB - The diagnostic work-up of atypical chest pain frequently leads to invasive procedures. However, this painful symptomatology can sometimes be of benign origin and respond to simple therapeutic manoeuvres. A number of musculoskeletal conditions such as costovertebral joint dysfunctions should be carefully considered. We report five cases in which patient discomfort and high costs could have been avoided if awareness of these conditions had led to a correct diagnosis upon initial physical examination. PMID- 1448408 TI - Acute renal failure in a case of paraquat poisoning with relative absence of pulmonary toxicity. AB - A 37 year old male presented after the ingestion of paraquat ('Gramoxone', 20% w/v). Plasma paraquat concentrations indicated that he had a greater than 50% probability of death. The patient survived following a period of acute oliguric renal failure and with only mild pulmonary toxicity. PMID- 1448409 TI - Occupational medicine in the National Health Service. PMID- 1448410 TI - Should clinicians accept management responsibilities? PMID- 1448411 TI - 'Pseudo-Alzheimer's' and primary brain tumour. AB - Primary brain tumour may present in the elderly purely as a dementing illness before the onset or detection of sensorimotor neurological symptoms or signs. Although neurological examination may indicate no definite signs, close attention to accepted DSM-IIIR and NINCDS-ADRDA diagnostic criteria for primary degenerative dementia and 'probable' Alzheimer's disease respectively will suggest a process other than a degenerative one. This was the case in two patients with primary brain tumour presenting clinically with dementing illness similar to but distinct from Alzheimer's disease. PMID- 1448412 TI - Miliary tuberculosis presenting with thyrotoxicosis. AB - A male patient is described who presented with thyrotoxicosis, and a large painful neck mass. From the excised mass and stomach aspiration Mycobacterium tuberculosis was cultured and a diagnosis of miliary tuberculosis was made. The thyrotoxicosis was attributed to tuberculous thyroiditis. PMID- 1448413 TI - Menetrier's disease in a child. AB - A case of Menetrier's disease in a 3 year old child presenting with subtotal pyloric stenosis and fatal outcome due to postoperative complications is reported. It is emphasized that although radiographic and gastroscopic studies are helpful, a full-thickness mucosal biopsy is essential for the diagnosis of Menetrier's disease. PMID- 1448414 TI - Primary renal renin secretion responding to angiotensin converting enzyme inhibition. AB - A case of primary renal renin secretion of probable neoplastic origin is reported. Investigation demonstrated renin secretion to be incompletely autonomous with suboptimal suppression to posture and hypervolaemia. Easy control of the hypertension and hypokalaemia was achieved with an angiotensin converting enzyme inhibitor. Such treatment may prove to be a preferable option to surgery. PMID- 1448415 TI - Massive gastric dilatation and acute pancreatitis--a case of 'Ramadan syndrome'? PMID- 1448416 TI - Urinary bladder carcinoma initially manifested as brain metastases. PMID- 1448417 TI - Bilateral tubercular psoas abscess mimicking bilateral hydronephrosis--the role of computerized tomography in the management. PMID- 1448418 TI - Enterobius vermicularis live adult worms in the high vagina. PMID- 1448419 TI - Delivery of plasmid DNA into mammalian cell lines using pH-sensitive liposomes: comparison with cationic liposomes. AB - We compare the transfection efficiency of plasmid DNA encoding either luciferase or beta-galactosidase encapsulated in pH-sensitive liposomes or non-pH-sensitive liposomes or DNA complexed with cationic liposomes composed of dioleoyloxypropyl trimethylammonium:dioleoylphosphatidyl-eth anolamine (1:1, w/w) (Lipofectin) and delivered into various mammalian cell lines. Cationic liposomes mediate the highest transient transfection level in all cell-lines examined. pH-sensitive liposomes, composed of cholestryl hemisuccinate and dioleoylphosphatidylethanolamine at a 2:1 molar ratio, mediate gene transfer with efficiencies that are 1 to 30% of that obtained with cationic liposomes, while non-pH-sensitive liposome compositions do not induce any detectable transfection. Cationic liposomes mediate a more rapid uptake of plasmid DNA, to about an eightfold greater level than that obtained with pH-sensitive liposomes. The higher uptake of DNA mediated by Lipofectin accounts for part of its high transfection efficiency. Treatment of cells with chloroquine, ammonium chloride, or monensin decreases (threefold) transfection using pH-sensitive liposomes and either has no effect on or enhances cationic liposome-mediated transfection. Therefore plasma membrane fusion is not the only mechanism available to cationic liposomes; in certain cell lines DNA delivery via endocytosis is a possible parallel pathway and could augment the superior transfection efficiency observed with cationic liposomes. PMID- 1448420 TI - Regional jejunal perfusion, a new in vivo approach to study oral drug absorption in man. AB - Recently a new in vivo approach in man, using a regional intestinal perfusion technique, has been developed. The perfusion tube consists of a multichannel tube with two inflatable balloons, which are placed 10 cm apart. The tube is introduced orally and the time required for insertion and positioning of the tube is approximately 1 hr. In the present study eight healthy subjects were perfused in the proximal jejunum on three separate occasions. The first two perfusion experiments used the same flow rate, 3 ml/min, and the third experiment used 6 ml/min. Phenazone (antipyrine) was chosen as the model drug. The recovery of PEG 4000 in the outlet intestinal perfusate was complete in experiments 1 and 2, but slightly lower (90%) when the higher flow rate was used. The mean (+/- SD) fraction of phenazone absorbed calculated from perfusion data was 51 +/- 12% (3 ml/min), 64 +/- 19% (3 ml/min), and 42 +/- 27% (6 ml/min) for the three experiments, respectively. The mean fraction absorbed estimated by deconvolution of the plasma data was 47 +/- 16%, 51 +/- 19%, and 38 +/- 26%, respectively. The effective permeability of phenazone was 5.3 +/- 2.5, 11 +/- 6.8, and 11 +/- 12 (x 10(4) cm/sec, respectively. We have shown that it was possible to establish a tight intestinal segment which behaved as a well-mixed compartment. The low perfusion rate of 3 ml/min was preferred, since it resulted in the lowest variability in absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448421 TI - Suppression of inflammation by cyclosporin A is mediated via a T lymphocyte independent process. AB - An athymic mutant rat strain was used to examine the hypothesis that modification of diseases with an inflammatory component by cyclosporin A (CsA) results from the suppression of nonspecific inflammatory mechanisms, rather than T-lymphocyte function, as is commonly inferred. Confirmation that the animal host was grossly depleted of T cells was obtained from anatomic and morphologic examination and functional tests of T-lymphocyte responsiveness. The experimental approach was to determine the effect of CsA on the course of experimentally induced infection with Escherichia coli, and extracellular pathogen. Host protection against this microorganism is dependent on an effective nonspecific inflammatory response. CsA administration prior to bacterial challenge resulted in a highly significant increase in bacterial numbers in the kidneys of both euthymic and athymic hosts. The data have provided a direct demonstration that modulation of the nonspecific inflammatory response by CsA can occur via a T lymphocyte-independent process. PMID- 1448422 TI - Microdialysis sampling for the investigation of dermal drug transport. AB - Microdialysis perfusion in vivo has the potential to be a powerful sampling technique in dermal and transdermal drug delivery studies. Characterization of a commercially available microdialysis probe in vitro considering relevant physiological parameters is a vital first step in the evaluation of microdialysis as a dermal sampling technique. In previous microdialysis studies, analyte concentration and neutrality have been implicated in altering microdialysis recovery. The recovery of a model compound 5-fluorouracil (5-FU) was investigated at several pH values and donor concentrations. The relative recovery of 5-FU by the microdialysis probe was affected by pH but not by donor concentration. To confirm further that the changing concentration and pH profile presented by the flux of 5-FU was not significantly altering microdialysis recovery, an experiment comparing direct and microdialysis sampling of a Franz diffusion cell receptor compartment was performed. Although the 5-FU concentration (0-686 ng/ml) and pH (7.40-7.24) changed substantially, the recovery of 5-FU was not adversely affected. To demonstrate the feasibility of dermal microdialysis, the flux of a commercial preparation of 5-fluorouracil was monitored utilizing a microdialysis probe implanted in excised rat skin in vitro. The results from the dermally implanted probe demonstrate the potential of the technique while establishing the limitations of the current microdialysis system. PMID- 1448423 TI - Acyclovir permeation enhancement across intestinal and nasal mucosae by bile salt acylcarnitine mixed micelles. AB - The purpose of this study was to investigate the absorption enhancement of acyclovir, an antiviral agent, by means of bile salt-acylcarnitine mixed micelles. The specificity, site dependence, palmitoyl-DL-carnitine chloride (PCC) concentration dependence, and effects of absorption promoters on acyclovir absorption via the nasal cavity (N) and four different intestinal segments of the rat, i.e., duodenum (D), upper jejunum (UJ), combined lower jejunum and ileum (LJ), and colon (C) were evaluated. The present study employed the rat in situ nasal and intestinal perfusion techniques and utilized sodium glycocholate (NaGC), three acylcarnitines, and their mixed micelles as potential nasal and intestinal absorption promoters. Acylcarnitines used were DL-octanoylcarnitine chloride (OCC), palmitoyl-DL-carnitine chloride (PCC), and DL-stearoylcarnitine chloride (SCC). All acylcarnitines and NaGC by themselves produced negligible enhancement of acyclovir absorption in the rat intestine, while OCC and SCC were totally ineffective in the nasal cavity. However, the mixed micellar solutions of NaGC with PCC or SCC could significantly increase the mucosal membrane permeability of acyclovir in the colon and nasal cavity. On the other hand, NaGC OCC mixed micelles slightly increased the absorption of acyclovir by both routes. When a mixed micellar solution of NaGC with PCC was used, the rank order of apparent acyclovir permeability (Papp; cm/sec), corrected for surface area of absorption, was N (10.54 +/- 0.62 x 10(-5)) > D (6.82 +/- 0.30 x 10(-5)) > LJ (2.90 +/- 0.08 x 10(-5)) > C (2.54 +/- 0.14 x 10(-5)) > UJ (2.30 +/- 0.22 x 10( 5)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448424 TI - Effect of loading on swelling-controlled drug release from hydrophobic polyelectrolyte gel beads. AB - The effect of oxprenolol HCl loading on the kinetics of polymer swelling and drug release from suspension-polymerized poly(methyl methacrylate-co-methacrylic acid) (PMMA/MAA) beads has been studied in detail. Within the range of variables studied, the polymer swelling rate increases with buffer pH and concentration. And an ionization-controlled swelling mechanism (analogous to the relaxation controlled mechanism) mechanism) seems to become more rate-limiting at higher buffer concentrations. At oxprenolol HCL loading levels below 17.8%, the drug release and associated dimensional changes (in pH 7.4) exhibit an extended quasi linear region despite the inherent limitation of spherical geometry. At higher loading levels, the drug release becomes faster and first-order in nature. This is apparently a result of the transition from a dissolved to a dispersed system above a percolation threshold (15-18% loading in the present study). As a result of competition from processes such as the reduction of bead dimension due to drug release and the dimensional increase due to polymer swelling and osmotic contributions from the drug, the transient bead diameter increases monotonically during drug release at loading levels up to 25.6%, whereas upon further increasing the drug loading, the bead diameter goes through a maximum during the early drug release, which eventually increases again as a result of the slow but continuous increase in polymer swelling due to further ionization. In all cases, both the drug release and the dimensional changes approach completion as the penetrating ionization fronts meet at the center, indicating a true swelling controlled behavior. PMID- 1448425 TI - Metabolism, distribution, and transdermal permeation of a soft corticosteroid, loteprednol etabonate. AB - The soft corticosteroid, loteprednol etabonate (chloromethyl 17 alpha ethoxycarbonyloxy-11 beta-hydroxy-3-oxoandrosta-1,4-diene-17 beta-carboxylate), I, was designed based on the "inactive metabolite approach." Accordingly, I should be metabolized by hydrolysis to the corresponding inactive cortienic acid derivative, II. The in vitro and in vivo metabolism of I indeed yielded mainly this inactive metabolite, which is more hydrophilic and thus readily eliminated from the body. Relatively high levels of I were found in tissues after intravenous administration of the drug in rats. The permeability of I through hairless mouse skin was comparable to what has been found for related "hard" steroids, without significant metabolism taking place in the skin. PMID- 1448426 TI - Molecular weight changes in polymer erosion. AB - We report a study of the effects of polymer molecular weight on the erosion of polyanhydride copolymer matrices composed of 1,3-bis(p-carboxyphenoxy)-propane (CPP) and sebacic acid (SA) in aqueous solution. The erosion profile characteristically displays an induction period during which the erosion rate is relatively slow. The length of this period depends on the initial molecular weight of the polymer. The induction period may be characterized as a time during which a rapid decrease in polymer molecular weight occurs, the end of this period correlating with the time required for the polymer molecular weight to decrease to below a value of approximately 5000 (MW). PMID- 1448427 TI - Dose proportionality of transdermal nitroglycerin. AB - The FDA Cooperative Efficacy Study of transdermal nitroglycerin utilized a combination of marketed products over a wide dose range. Unfortunately, plasma nitroglycerin concentrations were not determined. The current study was conducted to assess plasma nitrate concentrations after transdermal doses of 15, 30, 60, and 105 mg/24 hr employing the FDA Cooperative Study design. Plasma concentrations of nitroglycerin, 1,3-glyceryl dinitrate, and 1,2-glyceryl dinitrate were determined during the 24 hr of application and for 1 hr after transdermal system removal. Dose proportionality was assessed after normalizing the data by theoretical dose. For nitroglycerin, dose-normalized AUC(0-infinity) and Cmax were higher for the 105 mg/24 hr dose than for the other doses. For the metabolites, 1,3-glyceryl dinitrate and 1,2-glyceryl dinitrate, there were no differences in dose-normalized AUC(0-infinity) and dose-normalized Cmax between the dose levels. No differences were seen in Tmax between the dose levels for all three species. Based on the dinitrate metabolites, dose proportionality was seen over the 15 to 105 mg/24 hr dose range. Nitroglycerin, however, was found to be linear only between 15 and 60 mg/24 hr. PMID- 1448428 TI - Metabolism of testosterone during in vitro transport across CACO-2 cell monolayers: evidence for beta-hydroxysteroid dehydrogenase activity in differentiated CACO-2 cells. AB - Testosterone has previously been used as a model compound for the determination of unstirred water layer thickness in the CACO-2 transport model. We have found, however, that testosterone is metabolized during in vitro transport across the CACO-2 cell monolayers. This suggests that testosterone is not an ideal model substance. Testosterone is metabolized to androstenedione, indicating the formation of 17-beta-hydroxysteroid dehydrogenase by differentiated CACO-2 cells. No reverse metabolism is observed, thus androstenedione is considered superior to testosterone for determination of unstirred water layer thickness in the CACO-2 system. Permeability coefficients for testosterone and androstenedione obtained under identical transport conditions were 66 (+/- 7) * 10(-6) (n = 26) and 84 (+/ 7) * 10(-6) (n = 9) cm/sec, respectively. The unstirred water layer thicknesses at different agitation rates are determined for the CACO-2 transport model used in our laboratory utilizing androstenedione as a model compound. The system is capable of controlling the water layer thickness from about 200 to 1000 microns. PMID- 1448429 TI - High-dose methotrexate does not affect the pharmacodynamics of phenobarbital hypnotic action but decreases the central nervous system (CNS) sensitivity to pentylenetetrazol-induced maximal seizures in rats. AB - Chemotherapy with high-dose methotrexate (HD-MTX) is often associated with acute neurotoxicity. We determined whether the altered neuronal function after HD-MTX [such as the reduced regional cerebral metabolic glucose rate (rCMRGlc) and slow electroencephalographic pattern] affects the sensitivity of the CNS to centrally acting drugs: the depressant phenobarbital, which reduces rCMRGlc, and the analeptic agent pentylenetetrazol (PTZ), which elevates rCMRGlc. Adult male Sabra rats received an i.v. infusion of MTX, 0.51 mg/min, to induce neurotoxicity or saline solution for 24 hr. Subsequently, MTX-treated and control groups were infused in one experiment with phenobarbital until loss of the righting reflex and in the second experiment with PTZ until the onset of maximal seizures. HD-MTX did not affect the infused hypnotic dose or serum, brain, and cerebrospinal fluid concentrations of phenobarbital at the onset of anesthesia. The convulsive dose and PTZ concentrations in the serum and brain at the onset of maximal seizures were significantly higher in the HD-MTX-treated animals. These outcomes indicate that HD-MTX and the reduced rCMRGlc that follows this treatment do not contribute to the hypnotic action of phenobarbital. On the other hand, treatment with HD-MTX exhibited anticonvulsant properties as evidenced by the reduced CNS sensitivity to PTZ-induced seizures. PMID- 1448431 TI - General treatment of the enterohepatic recirculation of drugs and its influence on the area under the plasma level curves, bioavailability, and clearance. AB - A general treatment of enterohepatic recirculation of drugs has been developed based on the fraction of drug in systemic circulation that is excreted in the bile and the fraction of drug reabsorbed from the gut that reaches systemic circulation in each enterohepatic cycle. The deduced equations make it possible to establish mathematical relationships between the areas under the blood level curves (AUC) of a drug when administered to normal and bile duct-cannulated animals and to predict the effect of enterohepatic recycling on bioavailability and clearance. The results were compared with those obtained by other authors using different approaches to enterohepatic recirculation, and some discrepancies were found in the equations describing the effect of enterohepatic recycling on AUC and bioavailability of drugs. The cause of such discrepancies and the problems associated with the prediction of hepatic extraction ratio from in vitro studies are discussed. PMID- 1448430 TI - Studies on the excretion of diazepam and nordazepam into milk for the prediction of milk-to-plasma drug concentration ratios. AB - The influence of varying protein and fat content in milk of New Zealand White rabbits on the milk-to-plasma drug concentration (M/P) ratio of diazepam was studied. At various time points after littering, a bolus dose (1.5 mg/kg) followed by a 26-hr infusion (1.8 mg/h) of diazepam was administered to freely moving rabbits via a jugular vein catheter. Milk and blood samples were collected to allow characterization of milk composition and quantitative determination of diazepam and nordazepam in milk and plasma. At steady state diazepam showed M/P ratios between 3.7 and 9.5, whereas nordazepam showed ratios between 2.1 and 4.3, respectively. The relative importance of milk protein binding and milk-fat partitioning for the excretion of a drug into milk depended on the drug's affinity to milk fat. A stepwise multiple regression analysis suggested that observed M/P ratios of diazepam could be explained by considering the fat content of milk alone. Nordazepam with a lower solubility in milk fat showed M/P ratios which could be best explained by considering protein and fat concentrations together. Using the data from the infusion studies, two recently published diffusional models to predict M/P ratios were evaluated. Neither model could accurately predict the M/P ratios of diazepam and nordazepam observed in rabbits. However, after extending the model described by Atkinson and Begg to take the actually measured partitioning between skim milk and milk fat into account, a great improvement in the predictive power for observed M/P ratios occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448432 TI - A quantitative structure-activity relationship (QSAR) study of alkylpyrazine odor modalities. AB - The odor strength of a series of alkylpyrazines has been quantitatively investigated applying molecular connectivity, molecular shape, and the recently developed electrotopological state indices. The successful use of the latter parameters indicates that both electronic and topological features contribute to the odor strength of the compounds under study, while the specific role of the two nitrogen atoms is revealed. PMID- 1448434 TI - Microparticles of polyvinyl alcohol for nasal delivery. I. Generation by spray drying and spray-desolvation. AB - Spray-drying and spray-desolvation are described for the generation of polyvinyl alcohol microparticles intended for nasal administration. The spray-dried microparticles of polyvinyl alcohol were of an appropriate size distribution but consisted of hollow spheres, which made them unsuitable for nasal delivery, as rapid clearance and a varied deposition pattern would be expected. Microparticles were also produced by spraying polyvinyl alcohol (average molecular weight of 14,000) solution (12.5%, w/v) at 0.332 ml/min onto the surface of acetone (spray desolvation). These microparticles were solid collapsed spheres with the desired size for nasal deposition (10-200 microns). This method can be applied to encapsulation of drugs that are heat labile such as peptides and proteins. PMID- 1448433 TI - The effects of N(4-methylphenyl)diphenimide on lipid metabolism of Sprague Dawley rats. AB - N(4-Methylphenyl)diphenimide proved to be an effective hypolipidemic agent in rats at 10 and 20 mg/kg/day. Both serum cholesterol and triglyceride levels were reduced significantly. Decreases in tissue lipids as well as VLDL cholesterol levels were observed. HDL-cholesterol was elevated even at 10 mg/kg/day. The agent was equally effective in hyperlipidemic diet-induced rats, lowering serum lipids and VLDL- and LDL-cholesterol while elevating HDL-cholesterol levels. The drug interfered with the incorporation of 3H-cholesterol and 3H-palmitic acid into chylomicrons, VLDL, and LDL. The two precursors were incorporated at a higher rate into HDL. 3H-Leucine was incorporated into chylomicrons, VLDL, and LDL at a higher rate, but not into HDL. Reduced uptake of the precursor for lipid synthesis was noted in tissues after treatment with the drug. PMID- 1448435 TI - Participation of Macrogolstearate 400 lamellar phases in hydrophilic creams and vesicles. AB - In binary Macrogolstearate 400 (MS 400)/water systems, lamellar surfactant arrangements can be detected by polarized light and transmission electron microscopy. As demonstrated by X-ray diffraction and differential scanning calorimetry, the alkyl chains of the emulsifier are in the crystalline state. Ternary systems with liquid paraffin represent optically isotropic, homogeneous o/w creams for a wide composition range. Incorporation of up to 50 mol% cholesterol into the MS 400 lamellar structures leads to a gel-liquid crystalline phase separation within the bilayer, thus enabling the formation of spherical nonionic vesicles. The transition enthalpy of the samples decreases linearly with increasing cholesterol concentrations. The Macrogolstearate 400/cholesterol vesicles proved to be stable in hydrophilic cream systems. Cationic vesicles can be prepared using cetyltrimethylammonium bromide (CTAB) as a charge inducer. Low CTAB portions are inhomogeneously distributed within the bilayer, as detected by DSC. The results also indicate a perturbation of the alkyl chains packing for the positively charged vesicles. PMID- 1448436 TI - Benzoyl peroxide solubility and stability in hydric solvents. AB - Saturated solubility and reaction rate constants for the decomposition of benzoyl peroxide in solution and suspension were determined for use in formulation development. The solvents studied included ethanol, propylene glycol, and cosolvent mixtures of PEG 400 and water. The solubility of benzoyl peroxide was inversely related to the solvent polarity, with greater solubility occurring with semipolar solvents. The stability of benzoyl peroxide in solution was dependent on the solvent, concentration of benzoyl peroxide, and temperature. The compound was least stable in PEG 400. Stability was improved when water was added to PEG 400. Similar solvent effects were observed in suspension. In benzoyl peroxide suspensions of PEG 400 and PEG 400/water blends, benzoyl peroxide stability was dependent on solubility, with improved stability occurring in blends where the benzoyl peroxide was least soluble. Thus, solution formulations of benzoyl peroxide in pharmaceutically acceptable solvents are unlikely to show good stability; however, suspension formulations should be reasonably stable if the vehicle is selected to provide low benzoyl peroxide solubility. PMID- 1448437 TI - Predicting the effect of nonionic surfactants on dispersed droplet radii in submicron oil-in-water emulsions. AB - A novel theoretical model which describes the mass mean radius of oil droplets in an oil-in-water emulsion is described. A modified form of the Langmuir adsorption isotherm is used to account for nonlinear adsorption of surfactant to an oil water film and its effect on interfacial tension and oil droplet radius. On the basis of this model, the mass mean oil droplet radius may be related to bulk surfactant concentration for a nonionic surfactant. An analysis of the mineral oil-Triton X405-water system shows that aqueous solutions of Triton X405 against mineral oil behaved in accord with the proposed model. gamma m, the maximum interfacial tension lowering by Triton X405, was estimated to be 20.9 dyne/cm. A surfactant specific apparent constant (B) which relates the rate constant for adsorption to the interface to the rate constant for desorption from the interface into the aqueous bulk was estimated as 5.44E4 cm3/g. The pressure across the curved interface, delta P, was estimated as 1.05E6 dyne/cm2. The theoretical model appears to be consistent with experimentally observed oil droplet radii and is considered to be an accurate representation of the mechanics of dispersed droplet radii under conditions of moderate load of nonionic surfactant. PMID- 1448438 TI - Powdered solution technology: principles and mechanism. AB - The concept of powdered solutions can be used to formulate liquid medications in dry, nonadherent, free-flowing, and readily compressible powders. The technique is based on simple admixture of drug solution or liquid drug with selected carrier and coating materials. Improved drug release profiles are exhibited by such delivery systems even for poorly water-soluble drugs. Previous work using this method has rendered its industrial application impractical because of the unsatisfactory flow properties of the powder admixtures. This article presents a theoretical model based on the principles and mechanism of powdered solutions and introduces a new physical property of powders termed the flowable liquid retention potential (phi value). Mathematical expressions are derived that can be used to calculate the optimum amount of excipients required to yield powder admixtures with acceptable flowability. The validity and applicability of these expressions have been verified experimentally using clofibrate and prednisolone as test materials. The proposed model is shown to be superior to previously reported studies in optimizing the amount of excipients needed to prepare powdered solutions with acceptable flow properties. PMID- 1448439 TI - In vitro oral mucosal absorption of liposomal triamcinolone acetonide. PMID- 1448440 TI - Nasal absorption of leucine enkephalin in rats and the effects of aminopeptidase inhibition, as determined from the percentage of the dose unabsorbed. PMID- 1448441 TI - High-performance liquid chromatography determination of acitretin in plasma and its application to a pharmacokinetic study in human subjects. PMID- 1448442 TI - Excessive accumulation of hepatic copper in LEC rats aged 80 days without hepatitis and 130 days with hepatitis. AB - The Cu concentration was about 40 and 60 times higher in the liver in Long-Evans with a cinnamon-like coat color (LEC) rats aged 80 days (without hepatitis) and 130 days (with hepatitis), respectively than in the liver in Fischer rats. Most hepatic Cu was recovered in the cytosol fraction. Furthermore, about 96% and 84% of the cytosolic Cu was found in the metallothionein region on a Sephadex G-75 column in LEC rats aged 80 and 130 days, respectively. The hepatic metallothionein concentration was about 130 to 140 times higher in LEC rats than in Fischer rats when the concentration was expressed as metallothionein-bound Cu. Three forms of Cu-metallothionein were isolated by DEAE-cartridge. Although the concentration of hepatic Cu-metallothionein and its composition of polymorphic form were not changed greatly in hepatitis phase (in the 130-day-old LEC rats), activities of serum enzymes, aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) were increased significantly. The LEC rat showed a significantly low concentration of biliary Cu and markedly low activity of ceruloplasmin (as ferroxidase). Serum Cu showed a low concentration in the 80-day old LEC rats, but recovered to the control level in the 130-day-old LEC rats. The abnormal accumulation of Cu may be due to the inherent reduction of excretion of Cu into the bile and blood. Such deposition may be a trigger for the onset of the spontaneous hepatitis occurring at 90-120 days after birth and for the onset of hepatoma later. PMID- 1448443 TI - Experimental evaluation of the effects of pravastatin on electrophysiological parameters of rat skeletal muscle. AB - The effects of daily chronic treatment for 6 months with pravastatin was evaluated on the performance of the skeletal muscle system of different rat groups. At all doses (0.1 mg/kg-20 mg/kg) the righting reflex and the electromyographic signals observed in vivo did not show any abnormality. At the end of the treatment the Extensor digitorum longus muscles were dissected from treated and control rats and their passive and active electrical parameters were analyzed in vitro by standard microelectrodes technique. Pravastatin did not modify the chloride conductance nor the excitability characteristics of the fibers. Chronic treatment with pravastatin does not produce any alteration of skeletal muscle function. PMID- 1448444 TI - Mechanical effects of some prostanoids on isolated human oesophageal submucosal veins. AB - The effects of prostaglandins E1, E2, F2 alpha, prostacyclin, and the thromboxane A2-mimic U46619 were investigated on isolated human oesophageal submucosal veins from the oesophageal body and the oesophagogastric junction. U46619 most potently, but also PGF2 alpha produced venocontraction without differences between preparations from the oesophageal body and the oesophagogastric junction. PGE1 and prostacyclin caused relaxation of vessels precontracted with U46619 (10( 9) M). PGE2 induced either contraction or relaxation, but biphasic effects in the same vessel segment were not seen. Indomethacin 10(-6) M inhibited the contractile responses to both noradrenaline and K+ (124 mM), suggesting that the agonists induced synthesis or release of vasoconstrictor prostanoids. Prostanoids exert potent mechanical effects in submucosal oesophageal veins and may be of physiological importance. PMID- 1448445 TI - Bioactivation of halogenated hydrocarbons by rabbit pulmonary cells. AB - 1,1-Dichloro-2,2-bis (4'-chlorophenyl)ethane (DDD), 1,2-dibromoethane (DBE) and trichloroethylene are three halogenated hydrocarbons that selectively bind to pulmonary epithelial cells and that may be pneumotoxic. The susceptibility of pulmonary cells and the mechanisms of cytotoxicity of these compounds were evaluated using enriched subpopulations of isolated rabbit lung cells incubated with DDD, DBE, and trichloroethylene. These chlorinated and brominated hydrocarbons were studied to evaluate their ability to induce selective pneumotoxicity by their bioactivation in three cell types, i.e. Clara cells, alveolar type II cells, and alveolar macrophages. Evidence of cytochrome P-450 bioactivation was assessed by utilizing the suicide inhibitor, 1 aminobenzotriazole (ABT) to ameliorate cytotoxicity. DDD, DBE and trichloroethylene were cytotoxic to Clara cells, type II cells and alveolar macrophages and the order of cell susceptibility to DDD was Clara > type II > macrophages. DBE and trichloroethylene were nonselectively cytotoxic. ABT reduced the cytotoxic effects of DDD and DBE in Clara cells. These studies indicated that all three compounds were toxic to isolated lung cells and that bioactivation of DDD and DBE in rabbit Clara cells to a cytotoxic intermediate was mediated, at least in part, by cytochrome P-450 oxidation. PMID- 1448446 TI - Pharmacokinetics of the oxime HI-6 from a mixture with atropine sulphate in dogs. AB - The pharmacokinetics of the oxime HI-6 from an aqueous solution and from a mixture containing HI-6 and atropine (in doses similar as proposed for their combination in an automatic injector) was studied in German shepherd dogs. A standard manual injection of mixed drugs was followed by enhanced resorption of HI-6 while the elimination curves were quite similar. A comparison of the parameters describing relative bioavailability at the 80% probability level did not reveal any significant differences between the formulations of HI-6. The increase in HI-6 level in blood of animals receiving a mixture is more likely to be attributed to the local vasodilatation than to the systemic cardiovascular effects of atropine. PMID- 1448447 TI - Effects of toluene and n-hexane on rat synaptosomal membrane fluidity and integral enzyme activities. AB - The effects of toluene and n-hexane on rat synaptosomal membrane fluidity and the integral enzymes acetylcholinesterase (AChE) and ATPase were studied in vitro. The synaptosome membranes were isolated in Percoll and sucrose gradients. After adding toluene and n-hexane to the incubation mixture (37 degrees) in 2,4,6 and 8 mM concentrations, the fluidity changes were measured by the lateral pyrene diffusion method from Percoll-isolated membranes, and the ATPase and acetylcholinesterase activities were determined from both synaptosome isolations. Addition of toluene caused a linearly correlated increase of the synaptosomal membrane fluidity and a linear decrease of the AChE activity. The ATPase activity did not decrease linearly but dose-dependently. In contrast to the effects of toluene in vitro, addition of n-hexane in the same concentration range had no comparable influence on membrane fluidity nor on the activities of both integral enzymes despite its even higher lipid/water partition coefficient. Toluene increases synaptosomal membrane fluidity and at the same time inhibits the integral enzymes, probably by disturbing the lipid/protein interaction. PMID- 1448448 TI - Interaction between ciprofloxacin and thiopental in the central nervous system of the male rat. AB - The effect of intravenous ciprofloxacin (CPX) pretreatment on the kinetics and brain sensitivity for thiopental was studied in male rats using a previously developed electroencephalographic (EEG) threshold method. Thiopental was administered intravenously with constant infusion rate. Immediately after the appearance of the first burst suppression of 1 sec. or more (the "silent-second") in the EEG the infusion was stopped and the rats were killed by decapitation. The dose of thiopental needed to reach the criterion of silent-second was slightly reduced in ciprofloxacin pretreated rats when compared with saline pretreated controls. One rat that developed seizures after CPX pretreatment needed a considerably reduced dose of thiopental to induce the silent-second. The serum concentrations of thiopental were markedly reduced in the experimental group while no significant differences were found in the concentrations of thiopental in the different parts of the central nervous system (CNS), fat or muscle tissue. The kinetics of CPX were also affected. The experimental group (CPX + thiopental treated) had significant higher brain concentrations of CPX than the corresponding only CPX treated control group while no differences were found in the serum concentrations of CPX between the groups. As previously suggested, the distribution of thiopental in the CNS is not only dependent on its lipid solubility, but also as a weak organic acid, on the transport system for organic acids out of the CNS which both thiopental and ciprofloxacin seem to use and mutually compete for it. PMID- 1448449 TI - Effects of felodipine on utero-placental blood flow in normotensive rabbits. AB - The utero-placental blood flow was investigated in anaesthetized normotensive pregnant rabbits after repeated administration of a high dose of the antihypertensive calcium antagonist felodipine and in untreated controls. By means of the microsphere technique blood flow was also determined in the lungs, skin, intestine, skeletal muscle and kidneys during chloralose anaesthesia. Felodipine reduced mean arterial blood pressure, which was associated with a marked reduction in vascular resistance in the skeletal muscle vascular bed, where blood flow was increased seven-fold. In contrast, blood flow to placentae and kidneys were reduced. The pronounced reduction in placental blood flow may limit foetal nutrition and hence explain reported foetal digital defects after administration of high doses of felodipine to pregnant normotensive rabbits. PMID- 1448450 TI - On the pharmacological and physiological role of glibenclamide-sensitive potassium channels in colonic smooth muscle. AB - Actions of activators of glibenclamide sensitive K+ channels on canine colonic circular muscle were investigated. Cromakalim as well as its (-) enantiomer lemakalim caused inhibition of spontaneous phasic contractile activity (EC50's 4.4 +/- 0.1 x 10(-7) M and 2.3 +/- 0.4 x 10(-7) M, respectively) and of carbachol induced activity (EC50's: 9.4 +/- 5.1 x 10(-7) M and 4.3 +/- 1.4 x 10(-7) M, respectively). Cromakalim and lemakalim effects were completely inhibited by glibenclamide. Additive effects between K+ channel activators and other drugs relaxing colonic muscle (the L-type calcium channel blocker D600 and forskolin) were seen. A physiological role for specific glibenclamide sensitive K+ channels, if existing, remains unresolved. The present study indicates that the non adrenergic inhibitory nerves do not act through these channels, neither does stimulation of muscarinic or beta-adrenergic receptors. PMID- 1448451 TI - The effect of high calcium intake on intracellular free [Ca2+] and Na(+)-H+ exchange in DOC-NaCl-hypertensive rats. AB - The effects of calcium supplementation on blood pressure, intracellular free calcium concentration ([Ca2+]i) and rate of Na(+)-H+ exchange were studied in DOC NaCl-hypertensive rats. All the animals were uninephrectomized and divided into two main groups: the first group received deoxycorticosterone (DOC) (25 mg/kg, s.c.) once a week and had 0.7% NaCl as drinking fluid while the other received equal volumes of saline and tap water to drink. The animals were further divided according to dietary calcium intake: in the Control and DOC groups the chow contained 1.1% calcium, in the Calcium and DOC+Calcium groups, 2.5%. After 6 and 8 weeks, blood pressure in the DOC group was higher than in the Control group; on the other hand, the development of hypertension was attenuated in the DOC+Calcium compared with the DOC group. The Control and Calcium groups did not differ from each other. Platelets and lymphocytes were used as experimental models to study changes in the regulation of [Ca2+]i, evaluated by fluorescent indicators indo-1 and quin-2. In lymphocytes, basal [Ca2+]i was highest in the DOC group, but similar in DOC+Calcium and Control groups. In platelets, both basal and thrombin stimulated [Ca2+]i were higher in the DOC and DOC+Calcium groups than in the Control group. In both cell types [Ca2+]i was similar in Control and Calcium groups. In addition, platelets were used to study the ability of the cells to recover from intracellular acidification by first blocking the Na(+)-H+ exchange in a Na(+)-free medium and then restarting the exchange mechanism by increasing the extracellular Na+ concentration at constant speed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448452 TI - Bioavailability of two Soviet sustained-release theophylline formulations in comparison with TheoDur. AB - The pharmacokinetic parameters of two theophylline preparations of Soviet origin (Theobiolongas and Theopaek) were compared with the reference preparation TheoDur. The three sustained-release preparations were administered in a single oral dose (400 mg) to healthy volunteers. Blood samples were drawn over 36 hr and plasma concentrations of theophylline were measured by HPLC. Significant differences in the pharmacokinetic parameters were observed between the drugs. Compared to TheoDur, the two Soviet drugs, Theobiolongas and Theopaek, had lower bioavailability (86% and 82%, respectively), and higher rate of absorption. An 8 hr dosing interval should be preferred for Theobiolongas and Theopaek while twice daily administration appears to be appropriate for these preparations only in exceptional cases. PMID- 1448454 TI - Heterotopic autotransplantation of the distal pancreas segment after total pancreatectomy for cancer of the head of the pancreas. AB - Autotransplantation of the distal pancreas segment with pancreaticojejunostomy was performed in four patients with cancer of the head of the pancreas to preserve endocrine pancreatic function after extended total pancreatectomy. All patients had tumor involvement of both the celiac axis and the portal vein. The pancreatic graft was determined to be cancer-free by frozen section histologic and pancreatic juice cytologic examinations. The distal pancreas segment was autotransplanted to the iliac vessels heterotopically and placed in the extraperitoneal pocket to avoid untoward effects of any local recurrence or pancreatic leakage. This procedure, in the form of reconstruction, might be called modified subtotal pancreatoduodenectomy. Postoperatively, all patients remained normoglycemic without exogenous insulin administration, and their quality of life was considered satisfactory. PMID- 1448453 TI - Characterization of cultured human nesidioblasts and their associated macromolecules: cross-reactivity with a cloned rat pancreatic beta-cell line. AB - Near-total pancreatectomy in a neonate presenting with persistent hypoglycemia offered an unusual opportunity to grow preparations enriched in beta-cells. Morphology, chromosomal analysis, and immunohistochemistry were used to characterize a subculture (Nesi B) that remained stable through passage 11. Insulin secretion of Nesi B was constitutive at 38-74 nU/microliters of medium/24 h, increasing modestly in the presence of isobutylmethylxanthine, an inhibitor of cyclic AMP phosphodiesterase. Endocrine cells, exclusive of those in islet regions, were widely distributed throughout the original tissue section, and immunostaining of the Nesi B subculture demonstrated well-differentiated heavily granulated insulin-positive cells, each with a normal modal number of chromosomes (46). Nesi B cell-associated macromolecules were isolated in 3 x 10(-3) ethylenedinitrilotetraacetate/phosphate-buffered saline and were found to be reactive with a heterologous immune serum elicited to a cloned rat pancreatic beta-cell line (RIN-5F). Western (immuno) blotting showed this immunoreactivity to reside primarily in a 95-kDa fraction of Nesi B-derived components. These results indicate that human nesidioblasts can be cultured for a sufficient number of passages to allow isolation and immunochemical characterization of pancreatic beta-cell macromolecules shared between rat and human and that may serve as organ specific antigens for inflammatory disorders of the pancreas. PMID- 1448455 TI - A stereological investigation of rat endocrine pancreas after a long-term low protein diet. AB - Stereological analysis of rat endocrine pancreas was carried out after 4 months of low-protein intake. Thirty make Wistar rats, aged 2 months at the beginning of the experiment, were divided into three groups. The control group (NP) received a standard laboratory diet. The experimental group (LP) received a low-protein diet, and the pair-fed animals also received a standard laboratory diet, as the NP rats did, but restricted to the amounts consumed by the LP group. All groups were offered drinking water ad lib. Weibel's multipurpose lattice was used to determine the volume fraction of cells and numerical density of islets in the endocrine pancreas. The results showed that the long-term low-protein diet decreased the volume fraction of B-cells and increased that of A-cells. Numerical density of islets was significantly increased, whereas the absolute number was decreased. The mean number of B-cells per islet was found to be decreased and that of D-cells increased. The mean radius of the islets was decreased, as was the mean surface area. PMID- 1448456 TI - Element distribution in organelles of pancreatic acinar cells of rat, mouse, and pig investigated by energy-dispersive X-ray microanalysis. AB - The exocrine pancreas was long thought to be composed of identical subunits, the acinar cells that store the inactive forms of the digestive enzymes in zymogen granules (ZGs). These were generally seen as a homogeneous population of vesicles. This homogeneity was recently questioned: Digestive demands are answered by the release of specific enzymes and immunocytochemical labeling showed distinctive nonidentical populations of ZGs. We have aimed at finding concomitant differences in element contents. We analyzed by energy-dispersive x ray microanalysis (EDX) the subcellular distribution of elements in acinar cells of resting and stimulated rat, resting mouse, and resting pig pancreas and compared the results with values from the literature. We found large variances in the concentrations of Na, Mg, P, S, Cl, K, and Ca in cytoplasm rich in endoplasmic reticulum (C/E), whereas the concentrations of P, Cl, K, and Ca in mitochondria and ZGs had surprisingly small variations. Na and Mg were detected in measurable amounts only in C/E and mitochondria and Ca was detectable only in ZGs. We could not find any other elements. We have not found clearly distinguishable populations of ZGs. We critically discuss our findings in comparison with the literature. Many discrepancies can be explained by the different preparation procedures. We show that it is questionable to present absolute values of concentration in biological specimens on the basis of EDX. The technique should, in our opinion, be used only for the study of relative concentrations. PMID- 1448457 TI - Contribution of postprandial amino acid levels to stimulation of insulin, glucagon, and pancreatic polypeptide in humans. AB - The present study was designed to examine the contribution of the postprandial increase of plasma amino acids after ingestion of a protein-rich meal to the rise of the three pancreatic hormones insulin, glucagon, and pancreatic polypeptide (PP). A mixed amino acid solution was designed, which permitted a fairly close imitation of the arterial plasma pattern of the 21 amino acids that rise after ingestion of a 200-g porcine steak meal. In 10 healthy subjects the intravenous infusion of this mixed amino acid solution at a rate of 10 g/h elicited a rise of the 21 amino acids examined that correlated well with the postprandial increase (r = 0.89, p < 0.001). The maximal rise of plasma insulin (64 +/- 5 pmol/L) and glucagon (630 +/- 21 ng/L) was not significantly different from the postprandial increase of these two hormones (49 +/- 4 pmol/L and 780 +/- 28 ng/L, respectively). PP levels rose by 316 +/- 33 ng/L postprandially, which was clearly above the increase of 112 +/- 13 ng/L during intravenous amino acids (p < 0.01). In conclusion, the present data demonstrate that the postprandial rise of amino acid levels in arterialized venous plasma can account for most if not all of the postprandial increase of insulin and glucagon during the ingestion of a protein-rich meal. In contrast, only 35% of postprandial PP levels can be ascribed to the rise of plasma amino acids. In contrast to the effect of carbohydrate-rich meals, an enteric augmentation of insulin release seems to be of minor and possibly of no importance during ingestion of protein-rich meals. PMID- 1448458 TI - Expression of genes associated with dedifferentiation and cell proliferation during pancreatic regeneration following acute pancreatitis. AB - Pancreatic gene expression was analyzed in the rat during taurocholate-induced pancreatitis, with emphasis on the postacute phase where regeneration occurs. Increased expression of cellular oncogenes c-myc and H-ras followed a pattern typical of tissular regeneration. The c-myc protein was immunolocalized to acinar cells, in which amylase expression was concomitantly decreased. Such modifications in the program of gene expression and the presence of numerous mitotic figures confirmed participation of acinar cells in regeneration. There was, on the contrary, no evidence of duct cell proliferation and pancreatitis did not influence the expression of two mRNAs encoding ductal proteins. Expression of villin, which is a marker of the embryonic pancreas, increased by five times during pancreatic regeneration. The protein was localized to the tubular complexes, suggesting that cells forming those structures had returned to a protodifferentiated stage in which they should have recovered pluripotency. They might therefore supply the pancreas with any cell type needed to reconstitute functional parenchyma. PMID- 1448459 TI - Effect of total extrinsic denervation and atropine on HCl-stimulated pancreatic exocrine secretion and CCK release in conscious dogs. AB - In 10 dogs with pancreatic fistulas, we studied the effect of extrinsic pancreatic innervation and atropine on protein and bicarbonate secretion and cholecystokinin (CCK) release after intraduodenal perfusion with HCl. Before and after extrinsic denervation of the pancreas, the dogs were given 0.05 M HCl in increasing doses (1.5-48 mmol/h). Tests were repeated with atropine. Increasing doses of HCl resulted in a dose-dependent release of protein and bicarbonate output in both the intact and the denervated pancreas. However, pancreatic denervation significantly decreased pancreatic secretion in response to low loads but not to high loads of HCl. HCl-stimulated CCK release was not altered by pancreatic denervation. In the intact pancreas, atropine significantly reduced bicarbonate and protein response to low loads but not to high doses of HCl. In the denervated gland, atropine had no further inhibitory effect on exocrine pancreatic secretion. Furthermore, atropine showed no influence on HCl-stimulated CCK release under either condition. PMID- 1448460 TI - [The importance of Ginkgo biloba in European botany and pharmacy]. PMID- 1448461 TI - [Ginkgo biloba L., from the viewpoint of systematic and applied botany]. PMID- 1448462 TI - [The contents of Ginkgo biloba]. PMID- 1448463 TI - [Pharmacologic actions of Ginkgo biloba extract and contents]. PMID- 1448464 TI - Selective reduction by the 5-HT antagonist amperozide of alcohol preference induced in rats by systemic cyanamide. AB - This investigation was undertaken to determine the effect of a unique psychotropic agent on the volitional drinking of alcohol induced pharmacologically in the rat by an inhibitor of aldehyde dehydrogenase. Following administration of cyanamide in a dose of 10 mg/kg twice daily for 3 days, the pattern of drinking of ethyl alcohol was determined in each of 12 Sprague-Dawley rats by means of a standard preference test for 3-30% alcohol vs. water. Then, each rat was offered water and its maximally preferred concentration of alcohol, which ranged from 7-15%. After a 4-day predrug test, either the saline control vehicle or the diphenylbutylpiperazinecarboxamide derivative, amperozide, was administered subcutaneously. The injections of amperozide were given b.i.d. at 1600 and 2200 h over 3 days in a dose of 0.5, 1.0, or 2.5 mg/kg. The intake of alcohol during the sequence of amperozide injections was significantly reduced in a dose-dependent manner in terms of both absolute g/kg and proportion of alcohol to water intake, whereas the saline control vehicle was without any effect on alcohol consumption. Although the highest dose of amperozide reduced the total intake of fluid due to the sharp decline in alcohol drinking, neither the consumption of food nor level of body weight was affected by any dose of the drug either during or after its administration. Because amperozide acts centrally on the synaptic activity of dopaminergic and serotonergic neurons in limbic system structures, it is envisaged that the drug ameliorates the aberrant drinking of alcohol by virtue of a direct effect on either one or both of these classes of neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448465 TI - Ethanol and delta-sleep-inducing peptide: effects on brain monoamines. AB - The brain content of dopamine (DA) and its metabolites [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were the same in rats with different immobilization times in forced swimming test, while the serotonin (5-HT) concentration was higher in high active (HA, immobilization < 2 min) than low active (LA, immobilization > 5 min) animals. Ethanol (2 g/kg, PO) tended to increase the DA level in the striatum and nucleus accumbens in LA rats and decrease the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentration in HA rats. delta-Sleep-inducing peptide (DSIP) injection reduced the level of 5-HT in the medial prefrontal cortex (MFC) in both groups, did not affect the concentration of DA or DOPAC, but increased HVA in the striatum of HA rats. DSIP injected before ethanol administration augmented the ethanol effects on 5-HT in the MFC and attenuated the action of ethanol on 5-HIAA in the nucleus accumbens. A relationship between the different levels of voluntary alcohol consumption and sensitivity to stress among LA and HA rats and the differences in DA and 5-HT concentrations is suggested. The use of LA and HA rats in developing models for testing of stress-shielding compounds is also described. PMID- 1448466 TI - Effects of drugs on the temporal distribution of schedule-induced polydipsia in rats. AB - Drinking was induced in food-deprived rats by a fixed-time 1-min schedule of food presentation. With three rats, d-amphetamine (0.25, 0.5, 1.0, and 2.0 mg/kg) led to a dose-related increase in licking early in the interfood intervals, the peak of the temporal distribution of licking being shifted to earlier values. These effects were seen even when d-amphetamine had no effect on overall rates of licking and drinking. With another three rats, however, diazepam (0.5, 1.0, 2.0, and 4.0 mg/kg) did not shift the peak of the temporal distribution of licks in interfood intervals, even at doses that produced small increases in overall rates of licking and drinking. However, diazepam did reduce the peak of the distributions of licks at doses that did not decrease water intake and licks per minute. PMID- 1448467 TI - Behavioral effects of amphetamine and apomorphine after striatal lesions in the rat. AB - It is well established that denervation of the dorsal striatum by its dopaminergic afferents attenuates the stereotyped response to d-amphetamine, which can be considered as an extreme form of motor activation. However, it is difficult to sustain the view that this structure serves primary motor control function because the role of dopamine in the striatum remains difficult to understand. In this study, we compared the effects of two dopaminergic agonists, d-amphetamine and apomorphine, after dorsal striatal lesions with ibotenic acid using a computerized scoring of the behavior. Although d-amphetamine- and apomorphine-induced locomotor activity was no different between lesioned and nonlesioned rats in photobeam activity cages, the structure of their behavioral pattern was quite different. Freezing, a usual response after d-amphetamine, was blocked by the lesion. Lesioned rats exhibited less standing than nonlesioned after d-amphetamine, apomorphine, or saline treatment. Moving was increased in lesioned rats after a low dose of d-amphetamine (0.5 mg/kg) or apomorphine (0.5 mg/kg), while d-amphetamine induced in the same rats an increase of rearing. Stereotyped behavior after both drugs at high doses was not affected by striatal lesion. These results indicate that the dorsal striatum is not involved only in the control of stereotypy, as has been suggested using 6-hydroxydopamine lesions, but also plays a major role in the mediation of behavioral activation in response to stimulant drugs. PMID- 1448468 TI - Effects of angiotensin II on behavioral responses of defensive burying paradigm in rats. AB - The effects of angiotensin II (ATII) administered intracerebroventricularly in male Wistar rats in doses of 0.1, 0.5, and 1.0 micrograms, as well as of ATII (1.0 micrograms) + saralasin (SAR, an analog ATII) (5.0 micrograms), on behavioral responses of the defensive burying paradigm were studied. ATII-treated animals displayed significantly less defensive burying behavior (less time spent in defensive burying and less frequent burying than in vehicle-treated rats) in a dose-dependent manner. SAR at a dose of 5 micrograms did not affect burying behavior significantly; it also did not modify the inhibition effects of ATII on behavioral responses of the defensive burying test. These results provide evidence that ATII can exert anxiolytic actions on central transmitter systems mediating conditioned fear-related behaviors (i.e., defensive burying). The present study suggests that the defensive burying animal model is a rather sensitive test fulfilling the pharmacological criteria of dose-dependent sensitivity for studying the central effects of neuropeptides (e.g., ATII). PMID- 1448469 TI - Changes in spontaneous behavior in the dog following oral administration of L deprenyl. AB - An open-field activity test was developed for studying the effect of a single oral dose (range of 0.1-5 mg/kg) of L-deprenyl on spontaneous behavior in the dog. A computer program was used to quantify observations of locomotor activity, directed sniffing, urination, grooming, inactivity, jumping, rearing, and vocalization during a 10-min baseline and posttreatment session. Three dose dependent behavioral changes were observed: an overall decrease in directed sniffing, an increase in total locomotor activity in females, and a decrease in frequency of urination in males. These effects were only seen at the dose levels of 2 mg/kg or higher. Computer-assisted tracings of behavioral patterns showed increased stereotypical behavior and decreased exploratory behavior at the high dose levels. These behavioral effects are most likely due to either increased levels of phenylethylamine resulting from inhibition of monoamine oxidase B and/or the production of amphetamines as a result of the metabolism of L deprenyl. PMID- 1448470 TI - Further evidence for enigmas in adaptation mechanisms for the DOI-induced behaviors. AB - The acute and chronic effects of the 5-hydroxytryptamine2/1C (5-HT2/1C) receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the antagonist ketanserin were evaluated on the DOI-induced 5-HT2 receptor-mediated ear-scratch response (ESR) in mice. A challenge dose of DOI (2.5 mg/kg) administered 24 h following its first injection reduced the ESR frequency by 80 97%. The ESR score attained first injection value when the time lag between the first and the second injection was greater than 72 h. On the other hand, a single administration of ketanserin (1.0 mg/kg) caused no significant effect at 24 or 48 h but significantly reduced (51%, p < 0.05) the DOI-induced ESR 120 h following its injection. Chronic once-daily DOI injections reduced the ESR score by 80-97% throughout the treatment regimen. Following cessation from chronic treatment, the DOI-induced ESR frequency returned to control levels in a time-dependent manner. Repeated ketanserin administration significantly reduced the DOI-induced ESR score by 46% when tested 24 or 48 h following cessation of antagonist administration but had no effect at 78 h. Recently, we reported that 48 h following either a single DOI injection or termination from repeated DOI or ketanserin administration the DOI-induced head-twitch response (HTR) in mice exhibited supersensitivity. Thus, it appears that the DOI-induced behaviors exhibit differential adaptation mechanisms following either agonist or antagonist exposure. These studies further support our hypothesis that serotonergic drugs may have the ability to change independently the 5-HT-receptor sensitivity (signal transduction) and receptor density in the same or opposite directions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448471 TI - Unilateral, but not bilateral, locus coeruleus lesions facilitate recovery from sensorimotor cortex injury. AB - This study investigates the role of the locus coeruleus in recovery from sensorimotor cortex injury. Unilateral locus coeruleus lesions given 2 weeks prior to unilateral sensorimotor cortex injury facilitate subsequent motor recovery compared to animals with only a sensorimotor cortex injury, while bilateral locus coeruleus lesions severely retard motor recovery. The results suggest that recovery of function from the cortical injury is facilitated as long as a sufficient amount of the noradrenergic system remains intact, perhaps to provide a basis for compensatory sprouting. The results also suggest that recovery does occur in the absence of the locus coeruleus, indicating that the noradrenergic system is not necessary for recovery to occur after the cortical injury. PMID- 1448472 TI - Rodent model of nicotine abstinence syndrome. AB - Few animals models are currently in use for the recognized clinical problem of nicotine dependence and abstinence. This study introduces a rapid and convenient model using the rat. Sixteen male rats were rendered nicotine dependent by 7 days of continuous subcutaneous infusion of either 3 mg/kg/day (n = 8) or 9 mg/kg/day (n = 8) nicotine tartrate salt; 8 control rats were infused with saline alone. Rats were observed for 15 min before, during, and after the drug infusion period using a tally sheet modified from a standard checklist of opiate abstinence signs. There were few signs observed in any group at baseline and at the end of the infusion period. However, nicotine-infused rats showed a significant, dose related increase over the control group at 16 h after the end of infusion, largely subsiding by 40 h. The most frequently observed signs during withdrawals included: teeth-chattering/chews, writhes/gasps, ptosis, tremors/shakes, and yawns. A significant drop in locomotor activity and increase in weight gain following termination of nicotine infusion provided additional evidence of an abstinence syndrome. This syndrome was alleviated by SC administration of 0.4 mg/kg nicotine tartrate. PMID- 1448473 TI - Serial injections of MK 801 (Dizocilpine) in neonatal rats reduce behavioral deficits associated with X-ray-induced hippocampal granule cell hypoplasia. AB - MK 801 (NMDA antagonist) has been shown to protect newborns from hypoxia-induced brain damage. Here, we determined if (+)-5-methyl-10,11-dihydroxy-5h-dibenzo (a,d)cyclohepten-5,10-imine (MK 801) could attenuate behavioral deficits associated with early radiation-induced hypoplasia of fascia dentata granule cells. We pretreated neonatal rats (n = 20) with MK 801 (0, 0.1, or 0.2 mg/kg, IP) before each of eight fractionated, head-only doses of X-rays (13 Gy total) administered during the first 16 days postpartum. Other rats (n = 18) received the same drug treatments but were sham irradiated. At age 16 months, water-escape latencies to a submerged platform were measured in a water maze. Irradiated rats with hippocampal damage exhibited impaired learning (longer latencies to find the platform) than did sham-irradiated subjects. Moderate doses of MK 801 (0.1 mg/kg) facilitated the learning of the water maze by irradiated subjects but did not enhance the number of their fascia dentata granule cells. Higher doses (0.2 mg/kg) of MK 801 provided no behavioral benefits. In fact, this dose significantly impaired the learning of the water maze by sham-irradiated rats and potentiated the granule cell hypoplasia observed in irradiated subjects. Thus, early MK 801 treatment produces dose-dependent behavioral protection for rats with radiation-induced hippocampal damage. Future studies may reveal the neurophysiological and neuroanatomic substrates of this behavioral recovery. PMID- 1448474 TI - Strain and sex differences in amphetamine-induced rotation. AB - Studies of rotational behavior in female rats have investigated Fischer, Sprague Dawley, Madison, WI, and Holtzman strains. The present study of amphetamine induced rotational preference looked at the most widely used of the pigmented strains, Long-Evans hooded rats, examining rotation in females and comparing rotational magnitude and direction to males of the same strain. We corroborate in Long-Evans animals the greater rotation of females, but our findings oppose the right-sided female and left-sided male rotational preferences reported in earlier studies. Only female rats in this experiment had a significant directional bias, and it was to the left. This result strongly points to the importance of strain in the lateralization expressed by rotation. PMID- 1448475 TI - Acute and chronic morphine administration in swine. AB - Functional responses to acute and chronic morphine administration in domestic swine were examined and correlated with pharmacokinetic profiles. Acute effects of morphine sulfate were monitored in pigs for 24 h and the chronic actions of morphine alkaloid were monitored for 21 days. Serum morphine levels, nociception, locomotor activity, respiratory rate, body temperature, and body weight were monitored during all studies. To assess nociception in a large laboratory animal, a portable thermal stimulating device was constructed. Morphine sulfate administered IV and SC had a half-life of approximately 1 h whereas delayed release morphine alkaloid delivered SC had a half-life of 28 h. The degree of antinociception paralleled decline in blood morphine levels for both SC- and IV administered animals. Tolerance occurred to both antinociception as well as weight gain despite morphine levels remaining constant over the 21-day period. Morphine dependence was demonstrated by precipitation of an abstinence syndrome using naloxone. Animals in withdrawal displayed consistent signs, including wet dog shakes, posture changes, vocalization, and salivation. Collectively, these results indicate that swine may be reliably employed as a model to study the actions of morphine and opiate-like compounds. PMID- 1448476 TI - Effects of central administration of kynurenic acid on spontaneous locomotor activity in the kindled rat: a multivariate approach using the automated Digiscan monitoring system. AB - Changes in spontaneous motor activity in kindled hooded rats were measured following intracerebroventricular administration of three doses of kynurenic acid (65, 39, and 6.5 micrograms, dissolved in 3.3 microliters isotonic saline). Behavior was measured in the automated Digiscan system on every third day during 13 days of drug administration to assess initial behavioral impairment and the development of tolerance. Activity data were collected beginning 5 min after drug administration for six consecutive 5-min samples. The results revealed a suppressive effect of central administration of kynurenic acid on the pattern of spontaneous locomotor activity and showed the development of behavioral tolerance. Initially, the degree of suppression was dose related, but as tolerance developed group differences were minimized. Most measures returned to predrug levels by day 13 except vertical movement, which remained suppressed in the 65-micrograms group throughout testing. This measure may have been more sensitive to the subtle and long-lasting motor impairments resulting from kynurenic acid. PMID- 1448477 TI - Sensitization and individual differences to IP amphetamine, cocaine, or caffeine following repeated intracranial amphetamine infusions. AB - Rats that have a high locomotor response to novelty (HR) sensitize more readily to IP-administered amphetamine than rats with a low locomotor response (LR) to novelty. This experiment compared sensitization in HR and LR rats following amphetamine (3.0 micrograms/side for 5 days) infused bilaterally into either the nucleus accumbens (NACC), ventral tegmental area (VTA), or the medial frontal cortex (MFC). The subsequent locomotor response to IP-administered d-amphetamine sulfate (1 mg/kg), cocaine HCl (15 mg/kg), and caffeine benzoate (20 mg/kg) was also examined. No differences were observed between HR and LR rats following amphetamine infusion into either the MFC, NACC, or VTA. However, HR rats showed greater locomotor activity compared to LR rats following either IP amphetamine, cocaine, or caffeine for subjects cannulated in the NACC, MFC, or the VTA. Repeated infusions of amphetamine into the VTA increased the locomotor response to both IP amphetamine and cocaine, but not to IP caffeine, while repeated infusions of amphetamine into the NACC or MFC had no effect on locomotor response to any drug subsequently administered IP. The results support previous findings that changes induced by intra-VTA infusions, but not intra-NACC or MFC infusions, of amphetamine induce sensitization to IP-administered amphetamine and cocaine. Findings from the present experiment indicate the ability of the dopamine cell body region, but not the dopamine terminal fields, to produce locomotor sensitization to amphetamine and cocaine. The results from the present experiment also indicate the lack of localization to one of studied regions of individual differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448478 TI - 8-OH-DPAT in the midbrain central gray inhibits lordosis behavior. AB - Sexually receptive female rats were infused intracranially with 500-2,000 ng 8 hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the midbrain central gray (MCG), in the vicinity of the dorsal raphe nucleus (DRN), or directly into the DRN. When cannulae were located within the DRN, there was little evidence of change in lordosis behavior but a decrease in locomotor activity was commonly observed. In contrast, when cannulae were located anterior, ventromedial, or lateral to the DRN inhibition of lordosis behavior was rapid and robust. Both the lordosis-to-mount ratio (L/M) and the quality of the lordosis reflex were reduced following the infusion. The MCG receives lordosis-facilitating input from the ventromedial nucleus of the hypothalamus and from ascending sensory pathways and contributes information to descending motor systems involved in the lordosis response. Thus, the MCG is a critical link in the completion of the estrogen dependent lordosis reflex. The present results suggest that 5-hydroxytryptamine1A receptors in the MCG prevent the completion of this reflex. PMID- 1448479 TI - Peripheral serotonin is an incomplete signal for eliciting satiety in sham feeding rats. AB - Peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] to rats equipped with gastric cannulae reduced their 30-min consumption of sweetened milk after overnight deprivation whether the cannulae were closed (real feeding) or open (sham feeding). The anorectic action of 5-HT (1.6, 4.0, and 10.0 mumol/kg, IP) in sham feeding was dose-related, rapid in onset, and persisted during the 30 min testing session. However, 5-HT failed to elicit resting--the terminal behavioral phase of satiety--in sham-feeding rats. Direct comparison of the effects of 4.0 mumol/kg 5-HT under both feeding conditions established that this dose promoted resting only when rats fed with their cannulae closed. The actions of 5-HT on feeding and resting were behaviorally selective because serotonergic treatment did not retard the beginning of feeding, alter sham drinking of water, or reduce investigation by food-deprived rats of a novel object in an open field. Together, the results suggest that 5-HT exerts separate actions to inhibit feeding and accelerate the process of satiation as marked by resting. However, peripheral 5-HT is inadequate as a signal for modulating satiety in the absence of postingestive stimuli. PMID- 1448480 TI - Enhanced social interactions in rats following chronic, centrally infused oxytocin. AB - Most studies investigating the behavioral effects of centrally administered oxytocin (OT) have been confined to single acute injections followed by brief behavioral observations lasting up to 90 min. The present study examines the behavioral effects of chronic, centrally administered OT in male rats observed continuously for prolonged periods of time. Either artificial cerebrospinal fluid or OT was centrally infused (via osmotic minipump) to gonadally intact male rats. Behavioral observations were made on males paired with either ovariectomized or estrous females during a 6-h time period. Most striking was the observation that durations of physical contact were doubled in pairs containing OT-infused males, even in the absence of sexual interactions. Also, OT-infused males showed significantly higher levels of anogenital sniffing of females and autogrooming; however, sexual interactions were unaffected by chronic OT. Chronic OT had no effect on body temperature, analgesia, or exploratory behavior in an open field. These findings suggest that chronic OT in male rats has behavioral effects that may significantly enhance adult social (nonsexual) interactions, possibly through alterations in olfactory and somatosensory information processing. PMID- 1448481 TI - 5-HT3 receptor antagonists block cocaine-induced locomotion via a PCPA-sensitive mechanism. AB - We report results in rats pretreated with (+/-)-zacopride (0.03 mg/kg, IP), ICS 205-930 (0.1 mg/kg, IP), and MDL 72222 (1.0 mg/kg, IP) 15 min before challenge with (-)-cocaine (10.0 mg/kg, IP). At a dose of 10 micrograms/kg, zacopride significantly inhibited (approximately 50%) cocaine-induced locomotion. We also investigated whether or not 5-hydroxytryptamine3 (5-HT3) antagonists block the cocaine binding site on the dopamine transporter and/or affect the ability of dopamine to regulate this binding site. In well-washed striatal membranes, neither zacopride nor ICS 205-930 (10(-9)-10(-5) M) inhibited [3H]2 beta carbomethoxy-3 beta-(4-fluorophenyl)tropane ([3H]WIN 35,428) (0.3 nM) binding. Furthermore, neither of these compounds affected the ability of dopamine to block WIN 35,428 binding. To determine if 5-HT is required for the 5-HT3 antagonist effect, we examined the interaction between cocaine and zacopride in rats pretreated with p-chlorophenylalanine (PCPA) (3 days x 100 mg/kg/day). PCPA pretreatment shifted the cocaine dose-response curve to the right and blocked the ability of zacopride to reverse cocaine-induced activity. PMID- 1448482 TI - Central effects of monosodium glutamate on feeding behavior in adult Long-Evans rats. AB - Monosodium glutamate (MSG) is known as a neurotoxic molecule when injected neonatally in rats, where it produces a marked decrease in food intake and an increase in adipose tissue mass. But, in adult rats subcutaneous injections of MSG produce a small, dose-dependent increase in food intake. It is not known if this action is centrally or systemically mediated. Therefore, the feeding pattern of adult rats injected intracerebroventricularly with MSG was measured. Seven days after installation of a cannula in the right lateral ventricle, rats were injected either with artificial cerebrospinal fluid or twice with 3 mg/brain MSG within a 3-day interval. The feeding pattern was recorded via a complete computerized system during 24 h. Feeding behavior was significantly modified by MSG treatments. These effects were observed immediately after drug injections, that is, upon the first meal, as well as during the 24 h that followed. For the first meal, modifications in meal size (+285%; p = 0.0001), meal duration (x10; p = 0.0005), postmeal interval (x4; p = 0.0005), and the satiety ratio (-50%; p = 0.01) were observed. During the 24-h postinjection period, modifications in meal number (-3; p = 0.0007), total amount of food eaten (+21%,; p = 0.007), time spent eating (+40%; p = 0.007), meal duration (+53%; p = 0.005), and meal size (+44%; p = 0.01) were noted. When the two MSG injections were compared, differences were also noted. For the first meal, postmeal interval (-50%; p < 0.005) and satiety ratio (-50%; p < 0.005) were decreased after the second injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448483 TI - Differential effects of mesocortical, mesolimbic, and mesostriatal dopamine depletion on spontaneous, conditioned, and drug-induced locomotor activity. AB - Groups of rats with 6-hydroxydopamine (6-OHDA) lesions of either the medial prefrontal cortex (PFC), nucleus accumbens (NAC), or caudate putamen (CPu) were given daily tests for locomotor activity in photocell cages while food deprived. Two separate groups of NAC-lesioned rats were prepared with either large [NACT (90% NAC dopamine depletion)] or partial [NACP (67% NAC dopamine depletion)] lesions. NACT rats were spontaneously hypoactive whereas NACP rats were hyperactive compared with sham-operated controls. PFC-lesioned rats were also hyperactive compared to their respective controls. Spontaneous locomotor activity in CPu-lesioned rats did not differ from shams. When daily food supplements were paired with the photocell cages, all subjects developed a conditioned locomotor response. During the first few days of conditioning, the response to this conditioning procedure was markedly greater in the NACP group whereas the response in the NACT group was unaffected initially and actually enhanced during the latter days of testing. The locomotor response to the conditioning procedure was unaffected in either the PFC- or CPu-lesioned groups. Both the NACT and NACP lesions attenuated the locomotor response to 1.5 mg/kg d-amphetamine sulphate IP, and the NACT group showed a supersensitive response to 0.1 mg/kg apomorphine HCl SC. PFC or CPu 6-OHDA lesions did not alter the response to either drug. These results differentiate the role of PFC, NAC, and CPu dopamine in spontaneous, conditioned, and drug-induced locomotor activity and further implicate dopaminergic mechanisms of the NAC in the magnitude of the behavioural response to incentive stimuli. PMID- 1448484 TI - Effect of food deprivation and refeeding on the concentration of vasopressin and oxytocin in discrete hypothalamic sites. AB - Recent evidence has implicated hypothalamic peptides, such as arginine vasopressin (AVP) and oxytocin (OT) in the control of feeding behavior. In this study, we investigated the impact of food deprivation (48 h) and subsequent refeeding (6 h) on the concentration of AVP and OT in discrete hypothalamic areas, as well as in the neurohypophysis. We also estimated in these rats certain peripheral measures, including hydroelectrolytic parameters, plasma and urine AVP, and plasma corticosterone. The results of this study revealed that food deprivation for 48 h produced little change in OT concentration in the various hypothalamic nuclei studied, including the paraventricular and supraoptic nuclei, with the exception of the median eminence (ME), where a significant decline ( 36%; p < 0.05) was detected. This effect was not significantly reversed by 6 h of refeeding. With respect to AVP concentration, food deprivation caused a reliable decline exclusively in the parvocellular subdivision of the paraventricular nucleus (pPVN; -45%; p < 0.01) and in the supraoptic nucleus (SON; -45%; p < 0.01). No change in AVP was detected in the ME or in most other hypothalamic nuclei examined. Refeeding for 6 h actually potentiated the effect of food deprivation, decreasing further from baseline the content of AVP in the pPVN and SON. The only other hypothalamic area to exhibit a change in AVP content was the ventromedial nucleus, where AVP level increased (p < 0.001) after deprivation and declined to normal after 6 h of refeeding. The content of AVP and OT in the neurohypophysis was unaffected by food deprivation and subsequent refeeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448485 TI - Acute effects of marijuana on cognition: relationships to chronic effects and smoking techniques. AB - A double-blind, placebo-controlled study assessed acute effects on human cognition of marijuana smoking involving long or short durations of inhalation and breath holding. During eight test sessions, 48 adult, male volunteers completed standardized, pencil-and-paper tests of educational development and ability, as well as computerized tests of learning, associative processes, abstraction, and psychomotor performance. Marijuana impaired all capabilities except abstraction and vocabulary. These impairments were more pervasive than those associated with heavy, chronic marijuana use in a previous study involving the same tests, but showed some similarities. Marijuana altered associative processes, encouraging more uncommon associations. Marijuana-induced impairment in learning pairs of words was influenced by associative relationships between the words. There were a few hints that prolonged breath holding increased marijuana's effects under some test conditions, but in general it did not. Prolonged breath holding itself affected performance in four tests, regardless of whether subjects smoked marijuana or placebo. Whether physiological or psychological factors (e.g., exposure to carbon monoxide in smoke or subjects' expectations) produced these effects could not be determined. PMID- 1448486 TI - Vagally mediated feeding responses to phloridzin infusion in the rabbit. AB - Rabbits were infused with the plant glycoside, phloridzin, which blocks absorption of glucose across a number of bodily tissues. Feeding was dramatically increased in the first 0.5 h following phloridzin infusion into either the duodenum or the hepatic-portal vein of intact rabbits. Food intake covaried inversely with glycemic levels after phloridzin infusion into the hepatic-portal vein, but rabbits did not show a systematic relationship between blood glucose levels and food intake following duodenal infusion of phloridzin. When administered into the general circulation via the jugular vein, phloridzin did not elicit feeding. Finally, vagotomized rabbits did not show the hyperphagic response to phloridzin that was observed in intact rabbits. It was concluded that the feeding response to phloridzin is vagally mediated and appears to be induced by glucose transport inhibition at some peripheral site. PMID- 1448487 TI - Analgesic actions of local anesthetics and cobalt chloride in the rat brain stem. AB - A low-intensity thermally evoked tail avoidance reflex (LITETAR) was used to study changes in nociceptive response produced by local anesthetics and cobalt chloride microinjected into the dorsal posterior mesencephalic tegmentum (DPMT) of conscious rats. Dose-related prolongation of the LITETAR (e.g., analgesia) was observed when lidocaine, cocaine, and bupivacaine were administered into the DPMT. Analgesic actions were also demonstrated when cobalt chloride was microinjected into the DPMT. The analgesic actions of these different neuronal suppressants provide support for the hypothesis that there exists tonic activity of hyperalgesic processes in the rat brain stem. PMID- 1448488 TI - Distinguishing effects of cocaine i.v. and SC on mesoaccumbens dopamineand serotonin release with chloral hydrate anesthesia. AB - The effect of i.v. cocaine (0.5 and 1.0 mg/kg) was studied on synaptic concentrations of dopamine (DA) and serotonin [5-hydroxytryptamine (5-HT)] in the mesoaccumbens nerve terminal, the nucleus accumbens (NAcc), in chloral hydrate anesthetized, male Sprague-Dawley rats (Rattus norvegicus) with in vivo electrochemistry (voltammetry). In further in vivo voltammetric studies, the effects of SC cocaine on synaptic concentrations of DA and 5-HT were studied in the chloral hydrate-anesthetized paradigm in two neuroanatomic substrates, NAcc and mesoaccumbens somatodendrites, the ventral tegmental area (VTA-A10), in a dose-response fashion (10, 20, and 40 mg/kg) in six separate studies. Moreover, in two additional in vivo voltammetric studies, again using the chloral hydrate anesthetized paradigm, the impulse flow blocker, gamma-butyrolactone (gamma-BL) (750 mg/kg, IP), was studied alone and in combination with SC cocaine (20 mg/kg) to determine whether or not cocaine can act by presynaptic releasing mechanisms for DA and 5-HT. The results show that IV cocaine concurrently and significantly increased DA and 5-HT release in the NAcc (p < 0.001, p < 0.0005, respectively) at both doses tested. Moreover, IV cocaine effects on DA and 5-HT release were significantly and positively correlated (p < 0.01). On the other hand, SC cocaine concurrently and significantly decreased DA and 5-HT release in NAcc (p < 0.0001) and VTA (p < 0.0001) at each separate dose tested. SC cocaine effects on DA and 5 HT release were significantly and positively correlated across dose and neuroanatomic substrate (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448489 TI - Orally administered cyclo(His-Pro) reduces ethanol-induced narcosis in mice. AB - Cyclo(His-Pro) (cHP) is an endogenous, enzymatically resistant, biologically active peptide. We examined its ability to be absorbed after oral administration. cHP radioactively labeled with 125I (I-cHP) was fed to adult mice, and blood and tissue samples were taken 15-90 min later. Radioactivity quickly appeared in blood at levels about one half to one fourth those previously found after IV injection. The highest concentrations were in the kidney and liver, but the testes, muscle, lung, and brain also contained more radioactivity than was accounted for by their vascular spaces. Between 25-32% of the radioactivity recovered from blood 30 min after feeding eluted on high-performance liquid chromatography in the position of intact peptide. Oral cHP reversed ethanol induced narcosis, an effect previously found to occur within the brain. These results show that cHP can be absorbed orally in amounts sufficient to affect the CNS. PMID- 1448490 TI - The CCK-A receptor antagonist, devazepide, blocks the anorectic action of CCK but not peripheral serotonin in rats. AB - A role has been proposed for cholecystokinin (CCK)-A-type receptors in mediating the anorectic action produced by serotonergic stimulation in rats. We examined the effect of pretreatment with the CCK-A antagonist devazepide (DVZ) on anorexia produced by peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] or CCK-8 in 3-h food-deprived rats consuming a 30-min test meal of sweetened mash. The anorectic effect of CCK-8 (4.0 nmol/kg, IP) was antagonized in a dose dependent manner by DVZ (0.03, 0.10, and 0.30 mumol/kg, IP), with even the lowest dose producing a significant reversal. Under identical testing conditions, a supramaximal dose of DVZ (.75 mumol/kg) did not attenuate the reductions in food intake produced by either a moderate (4.0 mumol/kg) or a high dose (10.0 mumol/kg) of 5-HT. These data confirm established findings that the anorectic action of peripheral CCK depends upon CCK-A receptors. However, peripherally administered 5-HT reduces food intake independently of CCKergic function. PMID- 1448491 TI - Effect of oxiracetam on scopolamine-induced amnesia in the rat in a spatial learning task. AB - The effects of the nootropic agent 4-hydroxy-2-oxopyrrolidinoacetamide (oxiracetam) on memory and performance impairments induced by scopolamine were evaluated in the Morris water maze task. No effect was seen on the performance of rats when treated with oxiracetam (30 mg/kg, IP) alone. Task performance of scopolamine (0.2 mg/kg, SC)-treated rats was impaired as compared to that of control animals. The behavioral deficits expressed in the task by scopolamine treatment were attenuated by the same dose of oxiracetam. PMID- 1448492 TI - Estradiol modulation of the hyperphagia induced by the 5-HT1A agonist, 8-OH-DPAT. AB - Ovariectomized rats were primed with sesame oil or estradiol benzoate followed 48 h later by either sesame oil or progesterone. Four hours later, rats were treated with either saline or 0.25 mg/kg 8-hydroxy-2-9(di-n-propylamino)tetralin (8-OH DPAT). Rats were allowed to eat for 4 h after this final treatment. Animals in all hormonal conditions showed hyperphagia following 8-OH-DPAT. However, the hyperphagia was significantly attenuated by pretreatment with estradiol benzoate. There was no effect of progesterone on the hyperphagic response. These results suggest that previous findings of an estrous cycle modulation of the hyperphagic response to 8-OH-DPAT arise from the modulatory effects of estradiol, and not progesterone, during the female reproductive cycle. PMID- 1448493 TI - Serotonergic drugs do not substitute for clozapine in clozapine-trained rats in a two-lever drug discrimination procedure. AB - The atypical neuroleptic clozapine has been shown to have cue properties in two lever drug discrimination procedures. Although it has been demonstrated that clozapine acts at several types of receptors in vitro and in vivo, including dopamine, serotonin [5-hydroxytryptamine (5-HT)], and acetylcholine receptors, the mechanism of action for its discriminative stimulus properties has not yet been determined. The present study examined the effects of haloperidol (D2 dopamine antagonist), ritanserin (5-HT2 antagonist), 1-alpha H,3-alpha,5-alpha H tropan-3yl-3,5-dichlorobenzoate (MDL 72222) (5-HT3 antagonist), and buspirone (5 HT1A agonist) in stimulus substitution tests with rats trained to discriminate clozapine (5.0 mg/kg, IP) from vehicle in a two-lever drug discrimination procedure under a fixed ratio 30 schedule of food reinforcement. Analysis of the results revealed that, while clozapine produced dose-dependent responding on the clozapine lever, haloperidol and the three serotonin drugs failed to produce full substitution for clozapine at any of the doses tested. These results suggest that the discriminative stimulus properties are not mediated by D2 dopamine receptor blockade, antagonism at 5-HT2 or 5-HT3 receptors, or agonistic activity at 5-HT1A receptors. The neural basis of clozapine's discriminative stimulus properties has not yet been determined. PMID- 1448494 TI - Devazepide antagonizes the inhibitory effect of cholecystokinin on intake in sham feeding rats. AB - 3S(-)-N-(2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl) -1H indole-2-carboxamide (devazepide), a potent and selective cholecystokininA (CCKA) antagonist, has been shown to reverse the inhibitory effect of exogenously administered CCK-8 on food intake. In all tests, however, the inhibition of food intake could have been due not only to the CCK-8 administered but also to synergistic interactions between administered CCK-8 and endogenous satiety signals, such as glucagon or CCK released from the small intestine, elicited by the postingestive effects of the test diet. To eliminate these possible interactions, we investigated the effect of devazepide on the inhibitory effect of CCK-8 on the intake of a milk diet during 30 min of sham feeding, a procedure that minimizes or eliminates the postingestive satiating effect of food. Under these conditions, devazepide was a potent antagonist of the inhibitory effect of CCK-8 (16 mumol/kg, IP): The approximate ED50 was 625 ng/kg (1.3 nmol/kg) and the threshold dose was between 62.5 and 625 ng/kg. PMID- 1448495 TI - A versatile one-stage neurovascular flap for fingertip reconstruction: the dorsal middle phalangeal finger flap. AB - The dorsal middle phalangeal finger flap is an extremely reliable flap that is indicated for fingertip injuries which require sensory reconstruction. This flap originates from the dorsum of the middle phalanx of the finger and is elevated with a vascular pedicle of the digital artery and the dorsal branch of the digital nerve. After transfer of the flap to the injured site, epineural neurorrhaphy is done between the digital nerve and the dorsal sensory branch of the flap. This flap can be thought of as an island flap of the innervated cross finger flap that provides excellent sensory recovery and aesthetic improvement. We used this flap in a series of eight consecutive patients and were able to follow up seven patients for longer than 6 months (mean follow-up time 10.7 months). All patients achieved measurable two-point discrimination, with an average of 4.9 mm in the moving two-point discrimination. In this study, we report our consecutive series of the dorsal middle phalangeal finger flap and its versatile utility. PMID- 1448496 TI - Osteoid osteoma of the distal phalanx of the finger: a diagnostic challenge. AB - Osteoid osteomas of the distal phalanx of fingers are uncommon. An extensive review of the literature indicates that the diagnosis of osteoid osteoma of the distal phalanx is often delayed for several months to years (average 34.3 months). Pain is the most common finding (92 percent), followed by swelling and clubbing (75 percent). Relief of pain by aspirin was indicated in 10 patients (42 percent). Multiple operations were done in 7 patients prior to the appropriate diagnosis and treatment. A typical case report is presented to illustrate the difficulties in diagnosis and treatment of this benign bone tumor. A better awareness of this tumor may prevent unwanted delays in diagnosis and unnecessary operations. PMID- 1448497 TI - The effect of denervation on soft-tissue infection pathophysiology. AB - Pressure is the sine qua non in the etiology of pressure sores; however, ischemia, denervation, edema, and infection also have been implicated. The role of denervation in tissue infection was studied in an isolated in vivo ovine flap model. Twenty-six adult ewes, divided into three groups, had 29 island pedicle flaps raised on their buttocks. In group I, the cutaneous nerve remained intact, while group II had its nerve divided acutely. Group III had prolonged denervation, where the nerve was divided 7 days before flap elevation. All flaps received intradermal inoculations of 10(7) Staphylococcus aureus. Ninety-six hours later, quantitative bacteriology showed counts of 10(7), 10(7), and 10(9) colony-forming units (CFU) per gram of tissue in groups I, II, and III, respectively. Septic foci were larger in group III, and there was a significant increase in tissue edema between groups I and III. A 25-fold increase in bacterial counts seen in the prolonged denervation group may help explain why neurologically injured patients are more susceptible to infection and pressure ulcerations. PMID- 1448498 TI - The peripheral nerve allograft in the primate immunosuppressed with Cyclosporin A: I. Histologic and electrophysiologic assessment. AB - Nerve regeneration across peripheral nerve allografts and control autografts in primates immunosuppressed with Cyclosporin A was quantitatively evaluated by electrophysiologic and histologic methods. Twelve cynomolgus monkeys received 3 cm autografts and allografts in contralateral ulnar nerves. They were immunosuppressed with Cyclosporin A at 25 mg/kg per day or placebo vehicle. Morphometric analysis of nerve graft and distal nerve segments was assessed at 1 year after engraftment. Quantitative electrophysiologic studies were performed percutaneously at 6 and 12 months, and compound action potentials were measured directly across the nerve grafts at 1 year. Excellent regeneration was seen across autografts and allografts in Cyclosporin A-treated and placebo-treated recipients. PMID- 1448499 TI - The peripheral nerve allograft in the primate immunosuppressed with Cyclosporin A: II. Functional evaluation of reinnervated muscle. AB - Isometric contractile function was evaluated in primates receiving peripheral nerve allografts and autografts. Twelve adult male cynomolgus monkeys received both sural nerve allografts and autografts to the ulnar nerve in opposite forearms. Half the animals received Cyclosporin A (CsA) immunosuppression (25 mg/kg per day); the remaining animals received placebo. One year following nerve engraftment, isometric contractile muscle function was evaluated in reinnervated abductor digiti quinti and intact abductor pollicis brevis muscles. Maximal twitch tension (Pt), tetanic tension (P(o)), time to peak tension (tpt), rate of rise of twitch tension (DP/dt), and muscle fatigue were evaluated at optimal muscle length (L(o)). All reinnervated muscles distal to nerve autografts and allografts in both Cyclosporin A-immunosuppressed and placebo-treated animals generated equivalent maximal twitch tension, tetanic tension, and time to peak tension, with no significant difference between groups (p > 0.05 by ANOVA). There was a tendency toward increased muscle fatiguability in Cyclosporin A-treated animals (p > 0.05). However, the rate of rise of twitch tension was significantly faster in the reinnervated and intact muscles of Cyclosporin A-treated primates (p < 0.05). Evidence of excellent functional reinnervation across nerve allografts and autografts similar to that seen in histologic and electrophysiologic studies was noted. Cyclosporin A immunosuppression did not significantly enhance recovery of muscle function distal to nerve allografts in this model. PMID- 1448500 TI - An agenda for plastic surgery in the twenty-first century. PMID- 1448501 TI - Plastic surgery: generic or proprietary? PMID- 1448502 TI - AIDS, aesthetic surgery, and the plastic surgeon. PMID- 1448503 TI - Primary cutaneous cryptococcosis as the presenting manifestation of AIDS. AB - Presented is a case of primary cutaneous cryptococcosis, presenting as a papular facial lesion with subsequent ulceration, as the initial manifestation of AIDS. This unusual condition must be considered in the workup of unexplained or therapeutically unresponsive skin lesions. If it is diagnosed in an ostensibly "healthy" individual, evaluation for evidence of immunosuppression, and its underlying cause, must be undertaken. PMID- 1448504 TI - Mixed heterotopic gastrointestinal and respiratory cyst of the lip: case report and review of the literature. AB - A congenital heterotopic gastrointestinal and respiratory cyst arising from the upper lip is reported. The lesion was excised directly with a satisfactory aesthetic result. Long-term follow-up is recommended because of a report of recurrence of this type of lesion after 13 years. PMID- 1448505 TI - Spontaneous regression of subcutaneous metastasis of cutaneous melanoma. AB - A case is presented of a 44-year-old Caucasian man who was operated on in October of 1988 for a cutaneous melanoma in his trunk and who in the space of 1 year manifested a single subcutaneous nodule compatible with a metastasis of melanoma by fine-needle aspiration biopsy. No other abnormal findings were revealed by physical and instrumental examinations. During the subsequent hospitalization, we witnessed (in conjunction with the occurrence of painful symptoms in the hands of an inflammatory nature) the total, progressive, spontaneous regression of the metastasis, which was confirmed by the clinic and the tests. After 15 months of follow-up, the patient has not shown any further signs of illness. PMID- 1448506 TI - Papillary adenoma of the nipple. AB - Papillary adenoma of the nipple is a benign condition of the nipple that can be confused clinically with adenocarcinoma metastatic to the skin or Paget's disease. Deep biopsy of the nipple is necessary to make a histologic diagnosis. Complete excision of the nipple and the subareolar tissue is sufficient to effect a cure. PMID- 1448507 TI - Hook nail deformity repaired using a composite toe graft. AB - The hook nail deformity is caused by loss of fingertip bone and soft tissue. Healing can result in a volarly displaced distal nailbed and a tight tip with inadequate padding and a poor cosmetic appearance. A composite graft from the second toe placed beneath the released nailbed gives good support and improved pulp substance. The technique of the composite toe graft has been performed in nine patients. All grafts were 100 percent viable, but one patient required a second graft for additional tip bulk. There has been no donor-site morbidity in the follow-up of 1 month to 2 years. PMID- 1448508 TI - Permanent lip augmentation employing polytetrafluoroethylene grafts. AB - There is a paucity of literature regarding aesthetic enhancement of the lips. This is due to the lack of reliable techniques employing autogenous tissue and the reluctance on the part of surgeons to use an alloplastic implant in this anatomic region, which is superficial, subject to trauma, and must conform to innumerable geometric shapes. The ideal lip augmentation procedure should provide for a predictable, permanent enlargement without visible scars or donor-site deformity, can be customized to the particular patient's anatomy, and can be reversed if so desired. A series of 21 alloplastic lip implants employing polytetrafluoroethylene with a mean follow-up of 14.33 months is presented. The overall complication rate was 9.52 percent. Permanent lip augmentation can be achieved with alloplastic sheet grafts of polytetrafluoroethylene in a safe and predictable fashion. Stiffness of the lips develops with progressive thickness of the grafts. Grafts exceeding 3 mm in thickness should be avoided. PMID- 1448509 TI - The pronator quadratus muscle flap: coverage of the osteotomized radius following elevation of the radial forearm flap. AB - Skin-graft take following elevation of the osteocutaneous radial forearm flap has been shown to be difficult. The pronator quadratus muscle flap can be elevated to cover the exposed osteotomized radius and flexor carpi radialis and brachioradialis tendons. This technique is technically easy to perform and may significantly reduce donor-site wound-healing problems. PMID- 1448510 TI - Transiliac and retroperitoneal approach for coverage of sacrogluteal defects with inferiorly based rectus abdominis musculocutaneous flaps. AB - An inferiorly based rectus abdominis musculocutaneous flap is transferred to the sacrogluteal region through a transiliac approach. This technique is a simple and safe alternative to obtain a short pathway from the anterior abdomen to the sacral area. PMID- 1448511 TI - Consensus statement on the relationship of breast implants to connective-tissue disorders. PMID- 1448512 TI - Breast imaging for plastic surgeons. PMID- 1448513 TI - Nasotracheal intubation in patients with facial fractures. PMID- 1448514 TI - Treatment of facial paralysis. PMID- 1448515 TI - Gold eyelid weights in patients with facial palsy. PMID- 1448516 TI - Cold preservation of microvascular free flaps. PMID- 1448517 TI - Fixation of facial implants. PMID- 1448518 TI - A 3 1/2-year follow-up of a transplanted osteoarthrotendinous allograft covered with an autogenous flap for thumb reconstruction. PMID- 1448519 TI - Facilitating fetal rabbit surgery. PMID- 1448520 TI - Decreasing prolonged swelling and pain associated with deep plane face lifts. PMID- 1448521 TI - Endoscopic capsulotomy of capsular contracture after breast augmentation: a very challenging therapeutic approach. PMID- 1448522 TI - A maneuver to identify accurately the junction of the upper and lower lateral cartilage in the open rhinoplasty technique. PMID- 1448523 TI - Indirect intracranial volume measurement using CT scan. PMID- 1448524 TI - The experimental effect of low-energy laser on skin flap survival. PMID- 1448525 TI - A long-blade dissector set for calf augmentation. PMID- 1448526 TI - Reply to the editorial on AIDS, aesthetic surgery, and the plastic surgeon. PMID- 1448527 TI - Capsulectomy/local anesthesia by capsular insufflation. PMID- 1448528 TI - Reducing blood loss in reduction mammaplasty. PMID- 1448529 TI - Alterations in skin properties during rapid and slow tissue expansion for breast reconstruction. AB - This study comprises 23 women who had had mastectomies because of breast cancer. They were randomly divided into two groups when they were admitted for breast reconstruction by tissue expansion. The first group was expanded rapidly, i.e., every day, and the other group was expanded slowly, i.e., every week. There were no other differences in the treatment between the two groups. Three months after completion of expansion, the expander was replaced by a permanent prosthesis. The follow-up time was up to 6 months after the second operation. Three different parameters--distensibility, elasticity, and hysteresis--were measured noninvasively on the breast skin and at a control site on several occasions throughout the treatment. During the treatment period there were no differences in skin properties between rapidly and slowly expanded patients. Of the three parameters, distensibility showed the most prominent changes: decreasing during the expansion period, increasing after the expander had been replaced by a permanent prosthesis, and decreasing during the following 6 months. Elasticity did not change significantly, except decreasing after insertion of the permanent prosthesis, and the hysteresis increased at the same time. These findings indicate that tissue expansion alters breast skin only to a small extent and that the mechanical resistance sometimes encountered during tissue expansion is due to deeper structures such as underlying muscles or capsule formation. PMID- 1448530 TI - Holoprosencephaly and midline facial anomalies: redefining classification and management. AB - Holoprosencephaly encompasses a series of midline defects of the brain and face. Most cases are associated with severe malformations of the brain which are incompatible with life. At the other end of the spectrum, however, are patients with midline facial defects and normal or near-normal brain development. Although some are mentally retarded, others have the potential for achieving near-normal mentality and a full life expectancy. The latter patients do not fit clearly into the previously defined classification system. Proposed is a new classification focusing on those patients with normal or lobar brain morphology but with a wide range of facial anomalies. The classification aids in planning treatment. Coupled with CT scan findings of the brain and a period of observation, patients unlikely to thrive can be distinguished from those who will benefit from surgical intervention. Repair of the false median cleft lip and palate may suffice in patients with moderate mental retardation. Patients exhibiting normal or near normal mentality with hypotelorbitism and nasomaxillary hypoplasia can be treated with a simultaneous midface advancement, facial bipartition expansion, and nasal reconstruction. PMID- 1448531 TI - The use of scapular and parascapular flaps for cheek reconstruction. AB - This is a retrospective review of our experience with microvascular transfer of scapular and parascapular flaps for the correction of lateral facial contour deficiencies. Twenty-eight patients with congenital (n = 8) and acquired (n = 20) defects were treated with 30 flaps; two patients had bilateral flaps. The etiology of the defects included hemifacial microsomia (n = 2), oblique facial cleft (n = 1), Romberg's hemifacial atrophy (n = 5), neoplasm (n = 4), irradiation (n = 8), trauma (n = 4), tumor excision (n = 4), facial lipodystrophy (n = 2), and silicone granuloma (n = 2). The follow-up evaluation was from 2 to 13 years, with an average of 6 years. Fabrication of a facial moulage was part of the preoperative planning for each patient. These were compound flaps, including skin, deepithelialized skin, fat, fascia, and bone, if necessary. All flaps were constructed with an intact skin paddle for postoperative monitoring. Based on dissections and anatomic findings at operation, several variations in the level of emergence of the circumflex scapular artery from the triangular space and its branching patterns were noted. All flaps survived; changes in the patients' weights were reflected in the flaps. Twelve patients required secondary procedures: excision of skin monitor islands, scar revisions, debulking, or flap resuspension to the malar region. Bone grafts or alloplastic implants were necessary in four patients in whom the malar eminence could not be adequately corrected by transfer of a flap. The deepithelialized scapular/parascapular flap is preferred for correction of large lateral facial defects. PMID- 1448532 TI - Contralateral injections of botulinum A toxin for the treatment of hemifacial spasm to achieve increased facial symmetry. AB - Six patients noted facial asymmetry after botulinum toxin injection for hemifacial spasm. Each patient was injected on the side contralateral to the spasms with 10 to 15 IU over the zygomatic major and minor muscles. Each patient noted improvement in facial symmetry in the resting position and dynamic facial movements. Five of the six patients desired this approach with subsequent injections. This injection method variation proved helpful in the managing of hemifacial weakness created by botulinum A toxin for this condition. PMID- 1448533 TI - Long-term follow-up of the effectiveness and safety of inferior turbinectomy. AB - The long-term effectiveness and safety of inferior turbinectomy were assessed in 186 patients who were interviewed and examined 10 to 15 years after surgery (mean 12.3 years). Relief of nasal obstruction was reported by 82 percent of the patients; rhinoscopy showed wide, clean nasal airways in 88 percent. Rhinorrhea was still a problem for 34 percent of patients, and 19 percent were receiving medical treatment for this symptom. Smell acuity had improved in 52 percent of the patients. Before turbinectomy, 32 patients had suffered from bronchial asthma; postoperatively, there was an improvement in 16, and no change in 13; 3 patients reported exacerbation of asthmatic attacks. Atrophic changes of the nasal mucosa and chronic purulent infection were not observed in any of the patients. PMID- 1448534 TI - Hypertrophic sternal scars: silicone gel sheet versus Kenalog injection treatment. AB - A prospective, randomized trial was designed to compare the standard Kenalog injection of established hypertrophic sternal scars with topical silicone gel sheets (Spenco). Fourteen poststernotomy cardiac patients with symptomatic scars were randomized to treatment in one-half of the scar with Kenalog injection. Simultaneously, the other half of the scar received the silicone gel sheet. The standard Kenalog injection used was 40 mg/ml x 1 cc, mixed with 1 cc of 1% Xylocaine with epinephrine. The gel sheets were worn continuously for 12 hours for 12 weeks. Pretreatment and posttreatment photographs were compared for color and appearance by blindfolded observers. Scar measurements (length, width, and height) were taken weekly in each area, and the patients were asked to rank their symptoms within each half as worse, the same, or better. The primary outcome of patient preference was analyzed sequentially, and the recruitment was terminated after 11 patients had completed the study, 10 of whom favored the silicone gel treatment (p < 0.05). Three patients remained in the treatment phase at the time of termination and completed the study subsequently. For the total sample of 14 subjects, 11 preferred the silicone gel, 1 expressed no preference, and 2 preferred the injection. The average time to improvement was 3.9 +/- 0.62 days (gel) versus 6.8 +/- 1.86 days (Kenalog). This study demonstrates that silicone gel sheets provide earlier symptomatic relief and a more aesthetic scar and are the preferred treatment of patients with symptomatic hypertrophic sternal scars. PMID- 1448535 TI - Hypertrophic scar: an interruption in the remodeling of repair--a laser Doppler blood flow study. AB - Soft-tissue dermal loss does not regenerate; instead, it is replaced with scar. The extent of scarring is directly related to the severity of tissue loss (in terms of volume and depth). Commonly, an acute dermal loss will heal with excessive scar, hypertrophic scar. A hypertrophic scar is elevated but is contained within the boundaries of the initial injury. Hypertrophic scars have a reddish appearance, indicating an elevated local circulation. A laser Doppler blood flow monitor was employed to measure blood flow changes in healed wounds. It was speculated that local circulation in a developing hypertrophic scar would be elevated. Patients with recently healed wound sites were monitored and exhibited an average blood flow reading of 365 +/- 325 mV (n = 131). This average value, ranging from 98 to 1450 mV, was 18 times greater than the average reading from normal skin, which was 43 +/- 13 mV (n = 212). Blood flow declined to 32 +/- 21 mV (n = 7) at 16 to 18 weeks (74 percent of normal skin values) in healed wounds that developed normal scar. However, a closed wound that developed into a hypertrophic scar had a blood flow reading of 148 +/- 78 mV (n = 59) at 16 to 18 weeks. This value was three times greater than in normal skin and four times greater than in normal scar. At 38 to 50 weeks postinjury, hypertrophic scar remained elevated (102 +/- 34 mV; n = 10). Hypertrophic scars sustain an elevated blood flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448536 TI - Attitude of schizophrenics to computer videogames. AB - We investigated the initial attitude of 10 chronic, defected schizophrenic patients to a computer videogame session. Six of them enjoyed the experience and wanted to repeat it. Cooperation and performance were compared by means of videogames and a standard psychometric test (WAIS). Videogame performance correlated with the execution test IQ more than with the verbal test IQ. Computer games could be useful in these patients for evaluation of attitudes and responses, psychologic testing, motivation and reward. PMID- 1448537 TI - Determinants of recall of parental rearing behavior. The influence of age or loss of parents by separation or death. AB - In a study of 562 psychiatric inpatients and 251 healthy controls, relationships between age of proband and related life events (divorce of parents, death of a parent) and the perceived parental rearing have been investigated. The inverse relationships obtained could be explained by the higher number of divorced parents among younger subjects with negatively experienced parental rearing practices on the one hand and an idealization of the parents who had died on the other hand. In psychiatric patients these relationships and differences were more pronounced pointing to the importance of parental rearing as a vulnerability factor for mental problems during adulthood. The necessity to control for age in studies of perceived parental rearing became obvious by the present results. PMID- 1448538 TI - The Symptom Check List SCL-90-R and its ability to discriminate between dysthymia, anxiety disorders, and anorexia nervosa. AB - The factorial and discriminative validity of the Hopkins Symptom Check List SCL 90-R were examined in the light of criticism that clinical self-rating scales primarily express a general distress factor. In a population of 899 psychosomatic patients, high intercorrelations were found between the individual dimensions of the SCL-90-R. A subsequent Principal Components Analysis obtained 9 factors which were markedly less interdependent than those in the original version. The ability of the questionnaire to distinguish between patients with dysthymia, anxiety disorders and anorexia nervosa was examined. The average hit rate in the discriminant analysis was 67% using the original version and 74% with the proposed new factorial structure of the SCL-90-R, confirming the discriminative validity of the inventory. The present results as well as earlier studies suggest that the factor 'anxiety' should be included in the factor 'phobic anxiety', the factors 'paranoid ideation' and 'psychoticism' should be reformulated, and a new factor 'sleep disturbances' should be added to the original version of the SCL-90 R. PMID- 1448539 TI - Chronic psychoses and rehabilitation: an ecological perspective. AB - Traditional explanatory models, based on core psychological deficits, vulnerability-stress models or distinctions between negative and positive symptoms, may not be sufficient to understand the phenomenon of chronicity. This linear thinking, looking for monocausal explanations, should be replaced by exploring multicausal and circular processes over time, including the individual ecological context of a given patient. Thus, chronicity appears to result much more from endless loops and irreversible bifurcations in its dynamics over time than to be a stable state. Furthermore, the current views on psychopathology and prognosis need to be fundamentally reexamined in the light of this new way of thinking. For understanding and treatment of chronic psychoses, this ecological perspective implies programs which do not focus only on the patient, but look for 'ecological niches' and interventions favoring synergetics and self-organization within the social networks and at the worksite of a given patient. A recently implemented five-step program for vocational rehabilitation and the corresponding research plan will be presented and discussed. PMID- 1448540 TI - The Capgras syndrome in paranoid schizophrenia. AB - Capgras syndrome is characterized by a delusion of impostors who are thought to be physically similar but psychologically distinct from the misidentified person. This syndrome is generally thought to be relatively rare. Most of our knowledge about Capgras syndrome derives from single case studies and small series of cases usually from diagnostically heterogeneous groups. In this article, a series of 31 patients suffering from both paranoid schizophrenia and Capgras syndrome is described. Issues pertaining to the phenomenology of Capgras syndrome, the possible relation between Capgras syndrome and other delusional misidentification syndromes, and a neurobiological hypothesis aimed at explaining Capgras syndrome are discussed. PMID- 1448541 TI - Cycloid psychosis and affective disorder: borderland cases. AB - A subsample of untreated cycloid psychoses satisfying the requirements for major affective disorder according to DSM-III was compared with a subsample of cycloid psychoses getting other DSM-III diagnoses. The concept of cycloid psychosis applied thus was wider than permitted by the criteria stipulated by Perris and Brockington with respect to the prominence of the mood component. Since it could be demonstrated that no decisive differences prevailed with respect to frequencies of single features tested, a modified discriminant analytic procedure was applied. In this analysis, 76% of cases were correctly assigned. On average affective cases were more similar to the score profile derived from the nonaffective group than nonaffective cases were to the same profile, i.e. to themselves. Symptomatologically the affective cases had their main point in a distinctive confusion syndrome. PMID- 1448542 TI - The predictive value of thought disorder in manic psychosis. AB - Twenty-two patients with mania were evaluated for a variety of psychiatric phenomena. These items along with demographic data were used to predict relapse over a 36-month period in a multiple regression model. Formal thought disorder at the onset of illness was a strong predictor of relapse (F = 39, p < 0.001). The quality of the thought disorder was the most significant prognostic indicator. The predictive value of negative thought disorder was not enhanced by the addition of other symptomatic or demographic variables. PMID- 1448543 TI - AIDS and the ethics of medical care and treatment. Institute of Medical Ethics Working Party on the Ethical Implications of AIDS. AB - HIV infection and AIDS have accelerated a trend from paternalism to partnership in relationships between clinicians and patients. Partnership is based on respect for autonomy and is expressed through open dialogue; its moral aims are summed up in the concept of mutual empowerment. This has practical implications for clinical care and treatment, which are discussed here with particular reference to mental impairment or incapacity, unhelpful, harmful or unorthodox therapies, and discontinuing life-prolonging treatment. PMID- 1448544 TI - Wegener's granuloma. A series of 265 British cases seen between 1975 and 1985. A report by a sub-committee of the British Thoracic Society Research Committee. AB - In order to describe the British experience of Wegener's granulomatosis Hospital Activity Analysis was used to collect cases diagnosed in England, Wales and Scotland between 1975 and 1985. Where possible clinical details, histological material and chest radiographs were obtained. Two hundred and sixty five patients were considered to have Wegener's granulomatosis. In 109 a single pathologist confirmed the diagnosis by finding both granulomas and vasculitis in biopsy material. The diagnosis was made on clinical grounds or clinical grounds together with histological diagnosis in the local hospital in 156 patients. Wegener's granulomatosis was confined to the lung or upper respiratory tract in 22 per cent of patients and renal disease occurred in 58 per cent. Laboratory tests showed a pattern of mild anaemia, polymorph leucocytosis, eosinophilia and an elevated ESR and hypergammaglobulinaemia, with no specific pattern of changes. Histological confirmation was most frequently obtained by examination of nasal biopsy specimens, but multiple biopsies were often required. Renal biopsies showed focal proliferative glomerulonephritis but granulomatous glomerulonephritis was uncommon. Of available chest radiographs 61 per cent were abnormal, large opacities being most common. Small irregular opacities were found less often and other abnormalities were uncommon. Treatment varied widely and 10 per cent of patients received no drug therapy. This large series illustrates that even without specific treatment, patients with Wegener's granulomatosis can survive for several years and with modern treatment survival for more than a decade is possible. Conclusions about the effectiveness of the various therapies cannot be drawn from this retrospective study. Renal failure and disseminated vasculitis were the commonest causes of death; death was considered to result from complications of treatment with cytotoxic drugs or prednisolone in 6 per cent of patients. PMID- 1448545 TI - Clinical and histological spectrum of osteomalacia among Asians in south London. AB - In a prospective study of 175 adult Asian patients attending a medical out patient clinic we found a spectrum of metabolic bone disease. Twenty-four patients (13.5 per cent) had definite osteomalacia, of whom 11 (6 per cent) had severe clinical osteomalacia on the basis of associated symptoms and radiological signs. Fifteen (8.5 per cent) had borderline osteomalacia, while the remaining 136 (78 per cent) had normal bone biopsy, or were presumed to be normal. This histological spectrum was paralleled by the increasing prevalence of musculoskeletal symptoms (thigh pain, change in gait and difficulty rising from seated position) attributable to osteomalacia. Multivariate analysis showed that the major determinant of osteomalacia in Asians in South London was vegetarian diet. Increasing severity of bone disease was associated with increasingly strict vegetarian practice, which accounted for the excess risk of females, Hindus, and Asians originating from East Africa. Covering skin when outdoors also contributed to the female excess risk, and suggested a role for reduced solar exposure. Clinically significant osteomalacia is underdiagnosed in the Asian population, but evidence of dietary adaptation suggests this problem may diminish with time. PMID- 1448546 TI - Haemodynamic studies during the management of severe tetanus. AB - Detailed invasive haemodynamic studies were performed in 27 of 32 patients with severe tetanus. Nineteen had severe uncomplicated tetanus and eight had associated major complications, chiefly infection and pulmonary complications. The results were compared with those obtained from 15 healthy male volunteers who served as controls. There were two deaths in 32 patients (mortality 6.25 per cent). Severe tetanus without major complications was characterized by a high output hyperkinetic circulatory state with tachycardia (heart rate 131 (19.2) beats/minute), increased stroke volume index (43.1 (10.7) ml/m2), increased cardiac index (5.48 (0.94) l/min/m2) and a normal left ventricular stroke work index (60.5 (15.9) g/m/m2). Volume loading demonstrated a significant haemodynamic response and increased vascular capacitance. Even so the maximum percent rise from baseline values of these indices after volume load was significantly higher in controls (p < 0.001). Autonomic cardiovascular disturbances affected both sympathetic and parasympathetic activity. Hypertension and tachycardia alternating with hypotension and bradycardia were related to sudden fluctuations in systemic vascular resistance. Our studies suggested some degree of myocardial dysfunction in patients with severe uncomplicated tetanus. The haemodynamics of severe tetanus were masked and altered by complicating infection, pneumonia, and atelectasis. PMID- 1448547 TI - The immunogenetics of early nephropathy in insulin-dependent diabetes mellitus: association between the HLA-A2 antigen and albuminuria. AB - One-hundred and seventy-two normotensive, insulin-dependent diabetic patients without clinical proteinuria (Albustix negative) were typed for the major histocompatibility complex class I (HLA-A, -B) and class II (HLA-DR) antigens. Urinary albumin excretion was measured as the albumin:creatinine ratio (UA/UC, mg/mmol) in an early morning sample. Patients expressing the HLA-A2 antigen had significantly higher UA/UC values than those not expressing the antigen. The observed ratio of geometric means was 1.77 (95 per cent confidence interval (CI) 1.18-2.67; p < 0.01); the relative risk of microalbuminuria (UA/UC > 3.0 mg/mmol) associated with expression of HLA-A2 was 2.52 (95 per cent CI 1.11-5.73; p < 0.05). There was no significant association between UA/UC and HLA-B8, -B15, -DR3, -DR4 or other antigens. Patients were re-studied after a mean period of 5.3 years: multiple linear regression analysis showed that the UA/UC at this time was positively related to the initial glycosylated haemoglobin level (p < 0.01) and expression of the HLA-A2 antigen (p < 0.05), but not to blood pressure or creatinine clearance. Fifteen patients developed macroalbuminuria at follow-up (UA/UC > 45.5 mg/mmol). Compared with a group matched for age, sex, duration of diabetes, and glycosylated haemoglobin who did not develop macroalbuminuria, macroalbuminuric patients had a higher frequency of HLA-A2 (p < 0.01). The odds ratio of progressing to macroalbuminuria associated with HLA-A2 had a 95 per cent CI of 1.71 to infinity. We conclude that an immunogenetic factor may play a role in the development of early diabetic nephropathy and that the risk associated with expression of the HLA-A2 antigen is independent of metabolic control and blood pressure. PMID- 1448548 TI - A study of neuropathy in HIV infection. AB - A prospective study of possible aetiological factors for neuropathy associated with HIV infection was performed in 80 patients and 28 homosexual controls. At entry to the study twelve patients (15 per cent) had evidence of a generalized neuropathy not due to any other cause and a further three patients developed symptomatic neuropathy during a mean (SD) follow-up of 20 (7.5) months. All but two of these neuropathies were of the distal symmetrical sensory type. Electrophysiology was consistent with an axonal pathology and nerve biopsy confirmed this as the major pathological change. Warming threshold was the diagnostic test most frequently abnormal, sometimes in the absence of other electrophysiological abnormalities. No association was seen with opportunistic infection (cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis, Cryptococcus infection or tuberculosis). HIV proviral DNA could not be detected in paraffin sections of peripheral nerve in six patients with neuropathy. The presence of the neuropathy did not show significant correlation with depression of the number of CD4+ T cells in the blood, impaired T cell function tests, or IgG, IgM, or IgA levels. Immune complexes containing C1q, but not those containing IgG, IgM, IgA or C3c, were significantly more common among neuropathic patients (p = 0.01). PMID- 1448549 TI - [The biological effect of low-level radiation doses on the morphological composition of the peripheral blood in children]. AB - Examination of 339 children at the age of 2 to 12 years, living in the caesium contaminated region (from 2 to 5 Ci/km2) has revealed that total radioactivity of their urine is, on the average, twice as high as that of children living in "pure" regions. Quantitative and qualitative changes were observed in the erythroid series, neutrophilic leukocytes, eosinophils and B-lymphocytes of the peripheral blood of children subjected to long-term low-level irradiation. It should be noted that the character and direction of these changes were a function of the children's age and the level of total radioactivity of their urine. PMID- 1448550 TI - [The cytogenetic effect in peripheral blood lymphocytes as an indicator of the effect on man of factors of the Chernobyl accident]. AB - The data obtained confirm the possibility of both individual and population cytogenetic indication of the effect of low intensity radiation, exceeding the background level, and exhibit a positive correlation with the radio-ecological situation formed. The cytogenetic effect, that indicates the disturbance of the genome stability, might be considered as an indicator of a high probability of occurrence of pathologies, with a genetic component, in the subpopulations under study, compared to spontaneous level. PMID- 1448551 TI - [The ultrastructural organization of spruce needles of different ages exposed to radiation]. AB - The ultrastructure of mesophyll cells of spruce needle of different age within the region of Chernobyl catastrophe has been investigated. The quantitative characteristics of chloroplasts are shown to be a function of the absorbed dose rate. The effect of ionizing radiation on the processes of needle tissue ageing is discussed. PMID- 1448552 TI - [Radiologic and histologic study of trepanobioptates of the spongy bones in cattle in regions suffering as a result of the accident at the Chernobyl AES]. PMID- 1448553 TI - [The possibility of using the preparation MIGI-K in districts exposed to radioactive contamination following the accident at the Chernobyl AES]. AB - A preparation from mussels, MIGI-K, used as an additive to the diet of people working at the Chernobyl power plant has proved to be efficient in increasing the total resistance of the body, including the resistance to ionizing radiation. In experiments with animals, MIGI-K has been shown to accelerate excretion of 45Ca and 86Rb from the body. The combination of these properties of MIGI-K permits us to consider it an efficient drug to be used within the regions affected by the Chernobyl disaster. PMID- 1448554 TI - [Evaluation of the effect of the radioactive contamination of hydrobionts in the 30-kilometer control zone of the accident at the Chernobyl AES]. AB - A study was made of hydrobionts, particularly fishes, living within the thirty kilometer control zone of Chernobyl NPP and northern part of the Kiev basin, after the disaster. Out of 31 fish species living in the NPP cooling pond some were identified which were mostly affected by radioactive contamination. They were predators belonging, with respect to reproduction and development, to a lithophilous group. Peculiarities of reproduction of Hypophthalmichthys molitrix kept in stews of the cooling pond before the accident were studied. After a three year exposure to ionizing radiation (cumulative dose of 8-9 Gy) no reduction in the reproductive capacity of mature fishes was observed. PMID- 1448555 TI - [Results of the cytogenetic examination of the people taking part in the clean-up of the accident at the Chernobyl AES]. AB - Chromosome preparations from peripheral blood cells of 117 subjects who took part in liquidation of Chernobyl NPP accident consequences in 1986 have been investigated. The number of chromosome aberrations has been shown to increase considerably. A short-term exposure has been found to be 5-7 times more effective than long-term one. PMID- 1448556 TI - [The formation of DNA-protein cross-links in response to gamma radiation, UV irradiation and chemical agents]. AB - The present paper deals with the damages that are induced by numerous agents, such as gamma-radiation, UV-radiation, visible fluorescent light radiation, and a wide range of chemical agents, and lead to the formation of DNA-protein cross links. This is the most unknown and obscure type of damage to cells. It is, however, well known that these damages are reparable. PMID- 1448557 TI - [The modifying action of calcium antagonists on postirradiation thymidinemia]. AB - Single and long-term per os administration of verapamil, a calcium antagonist, changes the thymidine content of nonirradiated mouse blood. The changes observed depend upon verapamil concentration in the blood. The postirradiation thymidinemia level is the lowest in animals exposed at the time when the thymidine content was minimized by the agent administered. PMID- 1448558 TI - [The effect of ionizing radiation on the phospholipid content of fetal and maternal liver mitochondria at different stages of pregnancy]. AB - A single exposure of pregnant rats to 1 and 2 Gy radiation on days 3, 13 and 17 of reception changes the phospholipid content in membranes of liver mitochondria of fetus and maternal body. The changes are particularly pronounced on day 3 of reception: as the embryo grows the decline in the phospholipid content from the control level decreases. PMID- 1448559 TI - [The effect of biologically active substances on the structure and functional activity of liver nuclei of irradiated rats]. PMID- 1448560 TI - [The ciliated epithelium of the rat trachea is sensitive to gamma-irradiation in very low doses]. AB - As early as 5-7 min after the start of exposure of tissue preparations from rat trachea ciliated epithelium to gamma-radiation at a dose rate of 19 mGy/h, the ciliary motion rate increased periodically. The phenomenon of increasing the ciliary motion occurred more frequently in time; the intervals between two frequency drops became longer and the mean frequency level higher. The reverse sequence of the events was observed during the postirradiation period. The same regularities, but less expressed, were observed after irradiation at a dose rate of 1.8 mGy/h. PMID- 1448561 TI - [An experimental approach to determining the protective properties of drugs against ionizing radiation in low and sublethal doses]. AB - In experiments with mice, the efficiency of radioprotective agents against acute gamma-irradiation with nonlethal and low doses (0.5-4 Gy) was estimated by nine parameters. The treatment with cystamine, cysteamine and riboxine prior to irradiation (< 2 Gy) did not influence the postirradiation values of the parameters under study. With a dose of up to 4 Gy, the effect of riboxine was noted. The determinations of the number of aberrant mitoses, cellularity and mitotic activity of the bone marrow have proved to be most informative. The data obtained are discussed with due regard for the specific effect of low-level radiation and mechanisms of the protective action of the agents under study. PMID- 1448562 TI - [Characteristics of the dynamics of hematopoietic precursor cells cloned in diffusion chambers and recorded in experiments on mice and dogs irradiated in median lethal doses]. AB - In experiments with mice and dogs irradiated with LD50, it was shown the postirradiation depopulation of haemopoietic polypotent (CFUs) cell-precursors in mouse bone marrow was more pronounced than that of granulocytic and macrophagal cells (CFUdc). The rate of repopulation of CFUs during the first week was higher than that of CFUdc (T1/2 was 2.5 and 8.8 days respectively). In dogs, one could notice a partial change in the colony formation, a prolonged plateau period in the postirradiation CFUdc dynamics, and a coincidence in time with cellularity restoration in the bone marrow and peripheral blood leukocytes. It is suggested that in conditions of heterogeneous incubation in diffuse chambers, the haemopoietic cell-precursors are more mature than in the syngeneic system. The method of CFUdc determination has proved to be ineffective in estimating the onset and intensity of the postirradiation haemopoiesis recovery in dogs. The study of the bone marrow CFUdc population may, however, be used in intact animals to predict the probability of their death after irradiation within the median lethal dose range. PMID- 1448563 TI - [The radioprotective effect of hypoxia on clonogenic cells of rat bone marrow stroma (KOE-F)]. AB - A comparative study was made on the survival rate of cell-precursors of haemopoietic stroma, that form, in a rat bone marrow culture, colonies (clones) of fibroblasts (CFU-F) after gamma-irradiation of animals in the air or in a gas hypoxic mixture, containing 8% of O2 (GHM-8). Irradiation in GHM-8 was shown to increase the survival rate of CFU-F by 1.7 times (as compared to exposure in the air) as estimated by the total number of colonies that are formed in a culture; the radioprotective effect of GHM-8 was more pronounced for CFU-F which form dense colonies: DMF for dense and loose clones was 2.4 and 1.6 respectively. PMID- 1448564 TI - [The combined action of microwave irradiation and hypoxia on the biogenic amine content of the blood in guinea pigs in anaphylactic shock]. AB - The repeated effect of microwave radiation on guinea pigs was shown to arrest the anaphylactic shock and the related changes in histamine, epinephrine and norepinephrine content in the blood. The long-term adaptation of animals to hypoxia prevented this effect. PMID- 1448565 TI - [The modifying action of Sophora japonica and an antioxidant vitamin complex on acute radiation injury to the body]. AB - In experiments with mongrel male rats exposed to whole-body gamma-radiation (7, 9 and 11 Gy) the radioprotective effect of enterally administered Sophora japonica and its combination with an antioxidant vitamin complex was investigated. The radioprotective agents applied were shown to produce a synergistic effect. PMID- 1448566 TI - [The electronic structure and radiorprotective activity of a series of substituted iminodihydrofurans]. AB - Compounds that increase the survival rate of lethally exposed hybrid (CBA x C57B1/6)F1 mice have been revealed within the series of iminodihydrofurans. The quantum-chemical estimates, made by the MNDO method, show that substances which are capable of donor-acceptance interaction with DNA nucleotides and have the energy of donor orbitals, comparable with the electron structure of nucleotides, possess radioprotective efficacy. PMID- 1448567 TI - [Enzymes protecting the erythrocyte membrane during the combined exposure to an antioxidant complex and acute irradiation]. AB - The data are presented concerning the effect of ionizing radiation on the hemolytic process and the influence of an antioxidant vitamin complex on the pentosephosphate metabolism and glutathione reductase activity after gamma irradiation. The antioxidant vitamin complex has been shown to produce a favourable effect on the erythrocyte membrane stability in correcting the radiation-induced changes. PMID- 1448568 TI - [The role of fat-soluble vitamins A and E in preventing the biological effects of ionizing radiation in rat tissues]. AB - The lipid peroxidation level and the antioxidant system status have been studied by the amount of alpha-tocopherol and the antioxidant activity of homogenates in the brain, liver, heart and somatic muscle of rats given Vitamins A and E, as physiological additives, before and after gamma-irradiation. It has been shown that a new dynamic balance between the parameters under study is rapidly set up after irradiation, which represents a mechanism of rapid adaptation. The radioprotective effect of alpha-tocopherol is more pronounced than that of Vitamin A (particularly in the brain). In most cases, Vitamin A produces, upon irradiation, an unfavourable effect on antioxidative homeostasis. PMID- 1448569 TI - [Mathematical modeling of the dynamics of the intestinal epithelium in non irradiated and irradiated mammals]. AB - A mathematical model has been developed to describe the dynamics of the crypt villus system of the small intestine epithelium in nonirradiated and chronically irradiated mammals. The model involves the chalone mechanism of regulation of crypt cell reproduction and represents a system of nonlinear differentiation equations. The model presents the dynamics of the small intestine epithelium in nonirradiated animals, including stable fluctuations of the concentrations of crypt and villus cells (the limited cycle), and simulates quantitatively the impairment of the intestinal epithelium in small laboratory animals subjected to long-term irradiation. PMID- 1448570 TI - [The hematopoietic system during chronic irradiation with high dose rates (mathematical modeling)]. AB - Mathematical models have been developed to describe dynamics of some haemopoietic compartments in mammals subjected to long-term irradiation. Within the framework of the models developed an equation has been obtained for a critical dose-rate (Ncr) of chronic irradiation, leading to complete depletion of certain haemopoietic compartments, that helps to prognose the dangerous Ncr values without preliminary experiments. PMID- 1448571 TI - Politics, policy, and research. PMID- 1448572 TI - Meta-analysis of diabetes patient education research: variations in intervention effects across studies. AB - Data from a previously reported meta-analysis of diabetes patient education literature were reanalyzed to determine the influence of study/subject characteristics, such as study quality and age of subjects, on patient outcomes. Patient knowledge and self-management skills, weight loss, glycosylated hemoglobin levels, and psychological outcomes were analyzed as outcome variables. Seventy-three relevant published and unpublished studies were located. Patient education appeared to be more effective in younger patients, particularly for the knowledge outcome. For all patients, glycosylated hemoglobin levels improved between 1 and 6 months postintervention, but decreased to 1-month levels after 6 months. Length of the educational intervention did not appear to influence outcomes. More rigorous, experimental research designs tended to produce more conservative effect size estimates. Implications for diabetes patient education are discussed. PMID- 1448573 TI - A coercive interactional style as an antecedent to aggression in psychiatric patients. AB - As with society at large, violence in psychiatric settings is a serious clinical problem. Despite a great deal of attention, however, very little is currently known about the underlying theory or interventions to reduce aggression and violence in hospital settings. In this study, some psychiatric patients were viewed as having a general, aggressive, interactional style, motivated by the traits of Intimidation and Interpersonal Control, which when combined were labeled Coercion. A causal model in which violence and aggression were hypothesized to be predicted by a coercive interpersonal style and negatively predicted by an accommodating interpersonal style was tested. These interpersonal styles were proposed to mediate antecedent variables, that is, history of violence, psychiatric diagnoses, and length of hospitalization. Data were collected in two hospitals on psychiatric patients (N = 156) and analyzed using multiple regression techniques. The results of theoretical model testing suggested that 60% of the variance in Aggression was explained by four model variables: (a) Intimidation and Interpersonal Control (Coercion) (beta = .44), (b) Length of Hospitalization (beta = .26), (c) History of Violence (beta = .27), and (d) Bipolar Affective Syndrome (beta = .21). The implications for clinical care are discussed. PMID- 1448574 TI - The effect of diet consistency on food intake of anorectic tumor-bearing rats. AB - Delayed gastric emptying has been shown to occur in cancer patients complaining of anorexia and early satiety. Given that liquids are emptied from the stomach faster than solid food, the present study was undertaken to determine if diet consistency would affect food intake of hypophagic rats implanted with the Walker 256 carcinosarcoma. By Day 15 of tumor-growth, caloric intake of tumor-bearing animals was 20% less than controls. The caloric intake of tumor-bearing animals fed a liquid diet was not significantly different from animals fed a solid diet. Furthermore, a delay in gastric emptying was not seen in this animal model of tumor-induced anorexia. PMID- 1448575 TI - Women's perceptions of cesarean and vaginal delivery: another look. AB - Perception of the birth experience was examined in a sample of 106 women who had unplanned cesarean deliveries, 113 who had planned cesarean deliveries, and 254 who had vaginal deliveries. Vaginally delivered women had more positive perceptions than their unplanned cesarean counterparts (p < .001). There were no differences in perceptions between the unplanned and planned cesarean groups, or between the planned cesarean and vaginal groups. General anesthesia for cesarean delivery was associated with more negative perceptions than regional anesthesia, and regional anesthesia for vaginal delivery was associated with more negative perceptions than no or local anesthesia. Pain intensity and physical distress were negatively correlated with perceptions. PMID- 1448576 TI - Developing the construct of role integration: a narrative analysis of women clerical workers' daily lives. AB - There is a gap in nurses' knowledge about how women integrate their multiple roles on a daily basis amidst the economic, social, political, and cultural contingencies of their environments. Quantitative results from a triangulated study of work, maternal, and spousal role experiences of 87 women clerical workers from five ethnic/racial groups indicated that role integration was important in predicting health outcomes. This prior work is extended in this article with an indepth secondary analysis of the qualitative interview data from the same study to develop a theoretical understanding of the construct of role integration. Using techniques of narrative analysis, a theoretical framework was derived to identify and relate aspects, processes, and patterns of role integration as they are experienced in women's everyday lives. Concepts are identified, defined, and visually represented, propositions are elaborated, and implications for further research and practice are suggested. PMID- 1448577 TI - Knowledge of, attitudes toward, and barriers to pharmacologic management of cancer pain in a statewide random sample of nurses. AB - The knowledge of, attitudes toward, and perceived barriers to pharmacologic management of cancer pain were examined in a random statewide sample of nurses (N = 790), using an 82-item questionnaire. Although only 7% of the nurses reported working in oncology settings, 59% of the nurses reported having worked with patients with cancer in the last 6 months. The scores on the knowledge test ranged from 11% to 93% correct, with a mean percent correct of 56.4% (+/- .92). Nurses reported relatively liberal attitudes toward pain management, yet also reported believing that 22% of patients over report pain. Results are discussed with respect to implications for practice and education. PMID- 1448578 TI - Meta-analysis for descriptive research. AB - Although nurses have begun to use meta-analysis, a review of the nursing literature demonstrates that its use has not been maximized. Meta-analysis can be employed to synthesize descriptive as well as experimental research, yet attention in nursing has focused almost exclusively on meta-analysis techniques for, and meta-analytic studies of, experimental research. Furthermore, nursing literature has emphasized use of the effect size index (d) rather than the correlation index (r); the latter may, in some cases, be the more suitable metric, particularly with meta-analysis of correlational studies. An argument is made for the value of meta-analysis as a technique for integrating descriptive research, and an overview of different meta-analytic approaches to data analysis using the correlational index with descriptive research is provided. PMID- 1448580 TI - Hyperventilation syndromes. PMID- 1448579 TI - Nursing intervention studies require outcome measures that are sensitive to change: Part One. AB - In selecting an outcome measure for a study evaluating a nursing intervention, the criterion of sensitivity to change should predominate. Researchers commonly justify their choice of outcome measures for experiments based on such psychometric criteria as high internal consistency reliability and patterns of correlations reflecting convergent and discriminant validity. Although such criteria are appropriate for measures to assess individual differences, they are insufficient when the measures will be used for intervention studies. Researchers may need to develop new measures that are tailored for experimental studies if existing measures are valid mainly for the assessment of individual differences. In this first portion of a two-part article, three of seven factors to consider in selecting an outcome measure for an intervention study are outlined and recommendations for application of principles of reliability and validity in the context of sensitivity to change are given. PMID- 1448581 TI - Speculations on sarcoidosis. PMID- 1448582 TI - Prescribed respiratory diseases in the 1990s. PMID- 1448583 TI - Oxygen transport in the critically ill. PMID- 1448584 TI - Increased asthma admission rates in Asian patients: Blackburn 1987. AB - Asthma admissions for ages 1-44 for the year 1987 were studied to test the clinical impression that asthma admissions in ethnic Asians were more frequent than expected. Data on admissions was obtained from HAA statistics and from ward admission books. Population data was obtained from the 1981 Census with OPCS revisions and local epidemiological data of Asian births and new immigrant numbers. Admission rates per 1000 population were derived. Admissions were increased in Asian patients aged 1-4 years (odds ratio 1.18; 95% confidence interval 0.85-1.64) and 15-29 years (odds ratio 1.57; 95% confidence interval 0.83-2.98), but these increases were not significant. Admissions were significantly increased in Asian patients aged 5-14 (odds ratio 2.03; 95% confidence interval 1.32-3.12; 0.01 > P > 0.001) and 30-44 years (odds ratio 5.85; 95% confidence interval 3.66-9.35; 0.001 > P). The increased admission rate in Asians was not due to increased readmissions in the Asian ethnic group. The data supports the view that the difference in Asian admission rate may be due to a truly increased asthma prevalence in the Asian ethnic group. PMID- 1448585 TI - Evaluation of mean transit time in children as an indicator of airways obstruction. AB - Mean transit time was evaluated as a test of pulmonary function in normal and asthmatic children. It was found to be independent of body size and negatively correlated with PEFR, FEV1 and FVC in normal children. Mean transit time was less sensitive in detecting the effects of bronchodilator therapy in asthmatic children than other simpler tests of lung function. The range of normal was so wide that there was no clear demarcation between normal and abnormal. The degree of overlap makes isolated tests of mean transit time of little diagnostic value. It is therefore concluded that mean transit time though it theoretically offers the attractive advantage of being a sensitive indicator of both large and small airways obstruction, is unlikely to play a major part in the routine evaluation of lung function in asthmatic children. PMID- 1448586 TI - Relationship between inspiratory mouth pressure and respiratory muscle activity in normal subjects. AB - The relationship between inspiratory mouth pressure and respiratory muscle activation was investigated in 20 normal non-smoking subjects (13 males). Surface electromyography (EMG) was recorded from the seventh intercostal space bilaterally during different levels of inspiratory effort monitored by a respiratory mouth pressure gauge. The mouth pressure and EMG relationship was non linear between 20 and 100% of inspiratory effort. Quadratic regression analysis was performed between percent inspiration and percent EMG on each side of the chest. The regression equation and coefficient of determination (r2) for the right side were y = 9.73 (e0.024x-1), r2 = 0.91, and for left side were y = 10.79 (e0.023x-1), r2 = 0.88. An independent t-test did not reveal significant difference (P > 0.05) between the slopes of the regression lines from the two sides of the chest. Therefore, results of the two sides were pooled and the predictive regression equation for the combined results was y = 10.05 (e0.0236x 1). Reasons for such a non-linear relationship may include the loading mechanism of respiratory muscles, inefficiency of intercostal muscles at high levels of inspiration, their recruitment pattern and the histochemical characteristics of respiratory muscles. Since absolute EMG values cannot be used to assess changes in activation on different days, further work is required to establish the between-day repeatability of the technique described which is potentially useful for assessing respiratory muscle function pre- and post-operatively in chest surgery patients. PMID- 1448587 TI - A long-term prospective assessment of home nebulizer treatment. AB - Forty-nine patients (15 asthma, mean FEV1/FVC 1.3/2.1; 34 COPD, mean FEV1/FVC 0.7/1.8) were referred for consideration of home nebulizer treatment. All were monitored for 2 weeks while using their usual inhaled treatment followed by 2 weeks using a 'Nebuhaler' spacer to deliver 1 mg of terbutaline and 80 micrograms of ipratoropium bromide (IB) four times daily. They then borrowed a System 22 nebulizer to self-administer salbutamol nebulizer solution (5 mg), IB unit dose vials (0.5 mg) or a mixture of these drugs four times daily for 1 month each. Both asthmatic and bronchitic patients had a significant rise in their mean daily peak flow rate (PFR) during home nebulizer treatment (P < 0.03) and the COPD patients also had a significant PFR rise during Nebuhaler treatment (P = 0.0004). The mean daily peak flow rates (PFR 1 min-1 were: baseline 179, Nebuhaler 195, salbutamol nebulizer 200, IB nebulizer 198, mixed nebulizer 216). Four patients failed to respond subjectively or objectively to either Nebuhaler or nebulizer treatment. Five patients responded well to Nebuhaler treatment and did not proceed to a home nebulizer trial. Eight further patients preferred Nebuhaler to nebulizer treatment or could not tolerate nebulizer treatment (two cases). Thirty two patients requested home nebulizer treatment for long-term use (nine salbutamol, five IB, 18 mixture). Twenty-seven of these patients had an increased mean daily PFR (compared to their usual therapy) while using their chosen nebulized treatment. The mean increase in PFR for all 32 patients was 191 min-1 (11%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448588 TI - Relation of hypocapnic symptoms to rate of fall of end-tidal PCO2 in normal subjects. AB - Hyperventilation is of little clinical relevance unless it causes symptoms. These are often non-specific. Their threshold for onset and relation to steady level of arterial (or its equivalent, end-tidal PCO2; PETCO2) are uncertain, and it has been suggested that they may relate better to the rate of fall of PCO2 than to the absolute level. We investigated this in nine normal subjects, who breathed to and fro through a pneumotachograph into an open circuit in which the concentration of CO2 could be varied. Tidal volume, respiratory frequency and ventilation was measured on-line by a Compaq computer, and PETCO2 at the mouth was measured by capnograph. Subjects overbreathed at a fixed rate and depth until symptoms consisting of dizziness, paraesthesiae and light headedness occurred. Then, without their knowledge and while they continued to overbreathe, inspired CO2 was increased to restore PETCO2 to normal and abolish symptoms, and was then withdrawn again over either approximately 0.1, 2.5 or 5 min until symptoms were again reported. The PETCO2 at this point was noted. The three protocols were performed in each subject in a random order and the same symptoms were reported each time. When averaged across all subjects, symptoms occurred at mean PETCO2 values of 20.3, 19.2 and 18.6 mmHg (2.71, 2.56 and 2.48 kPa), respectively. These were not significantly different, and it can be concluded that there was no influence of rate of fall of PCO2 on threshold for symptoms. Chest pain only occurred in one subject and may have a different mechanism. PMID- 1448589 TI - Thoracic actinomycosis complicated by Actinobacillus actinomycetem comitans: case report and review of literature. PMID- 1448590 TI - Pulmonary alveolar-septal amyloidosis--an unusual radiographic presentation. PMID- 1448591 TI - Recurrent hyperventilation tetany due to mild asthma. PMID- 1448592 TI - Special treatment for serious asthma. PMID- 1448593 TI - Patient education, self management plans and peak flow measurement. PMID- 1448594 TI - Symptomatic hypercalcaemia in lung cancer. PMID- 1448595 TI - Regulation of calcitonin secretion and calcitonin gene expression. PMID- 1448596 TI - Surgical strategies and methods for the treatment of metastasizing medullary thyroid carcinoma. PMID- 1448597 TI - Pathology of sporadic and hereditary medullary thyroid carcinoma. PMID- 1448598 TI - Postsurgical follow-up and management. PMID- 1448599 TI - Epidemiology of medullary thyroid carcinoma. PMID- 1448600 TI - Tumor markers for the medullary thyroid carcinoma. PMID- 1448601 TI - Sporadic medullary thyroid carcinoma: clinical features and diagnosis. PMID- 1448602 TI - The impact of reimbursement issues on rehabilitation nursing practice and patient care. AB - Rehabilitation nursing practice and patient care are affected profoundly by reimbursement trends. This article provides a basic understanding of current and proposed reimbursement issues in Medicare, Medicaid, and private insurance- information that should help the rehabilitation nurse make the changes necessary to provide patient care within the constraints of the reimbursement systems. Furthermore, an understanding of these economic issues should assist nurses in working collaboratively and positively with administration while reducing their level of frustration. Nurses can play an important role in managing length of stay, using ancillary services, and moving the patient along the continuum of care, all of which are critical financial factors in a facility's successful management of its payer mix. PMID- 1448603 TI - Pressure ulcer prevalence and incidence in a rehabilitation hospital. AB - Pressure ulcers remain a serious health problem, especially in terms of personal suffering and economics. The study described here, conducted in a rehabilitation setting, investigated the prevalence (number of persons with pressure ulcers at a given time) and the incidence (number of persons developing pressure ulcers over a given time) of pressure ulcers. Skin assessments and risk assessments of the subjects were completed using the Braden Scale for Predicting Pressure Sore Risk. Demographic data were obtained. The prevalence rate was 25%, although there was no incidence during the time of this study. Factors associated with the prevalence of pressure ulcers are discussed. PMID- 1448604 TI - Metronidazole use in malodorous skin lesions. AB - Malodorous skin lesions (primarily fungating tumors and decubitus ulcers) can be extremely resistant to efforts to control their odors. The offending bacteria appear to be anaerobes, specifically the Bacteroides species. Topical metronidazole has shown promise for odor control without the cost or side effects of a systemic drug. In various anecdotal reports, lesions in patients treated with topical metronidazole were virtually free of odor within 24 hours, and in some cases, slight improvements in wound appearance and pain also were noted. The encouraging results of these initial experiences with topical metronidazole warrant further study for its efficacy in reducing skin lesion odor. PMID- 1448605 TI - The foot at risk: identification and prevention of skin breakdown. AB - This article presents the major predisposing factors and measures associated with preventing nosocomial foot lesions. The combination of nursing interventions and the appropriate use of protective devices can markedly reduce the incidence of foot lesions acquired in the hospital. Patient and family education is another important aspect in preventing skin breakdown of the foot at risk. PMID- 1448606 TI - Traditional Chinese medicine in rehabilitation nursing practice. AB - Traditional Chinese medicine (TCM) employs methods of treatment such as acupuncture, acupressure, and Qi Gong (treatment based on meditation). The nurse using TCM can affect rehabilitation patient outcomes positively. With TCM training, nurses have an opportunity to learn the nuances of the Oriental environment and integrate them into their skills to nurse the spirit, mind, and body of patients in a holistic manner. PMID- 1448607 TI - Nursing diagnoses used most frequently in rehabilitation nursing practice. AB - This article describes a study of 346 rehabilitation nurses in which the nurses identified the nursing diagnoses most frequently used in rehabilitation. The study identified patterns of diagnosis used by nurses in inpatient and community settings, found no pattern of use by educational background, and delineated etiologies used with diagnoses characteristic of rehabilitation nursing. PMID- 1448608 TI - Developing a safety plan that works for patients and nurses. PMID- 1448609 TI - Human responses to traumatic brain injury. AB - A traumatic brain injury can have devastating effects on the patient and the family. The patient with TBI faces deficits that influence life after hospitalization. With the use of specific nursing therapies, human responses to TBI can be treated and a patient can return to a satisfactory lifestyle. PMID- 1448610 TI - Rehabilitation: the global perspective. PMID- 1448611 TI - A case of lysogenic conversion: modification of cell phenotype by constitutive expression of the Mu gem operon. PMID- 1448612 TI - Construction of a broad host range shuttle vector for gene cloning and expression in Actinobacillus pleuropneumoniae and other Pasteurellaceae. AB - We have constructed a pair of broad host range expression vectors, pJFF224-NX and pJFF224-XN, based on plasmid RSF1010, which enable cloning and efficient expression of genes in Actinobacillus pleuropneumoniae and Pasteurella haemolytica and in Escherichia coli. The vectors consist of the minimal autonomous replicon of the broad host range plasmid RSF1010 and a type II chloramphenicol acetyl transferase gene for chloramphenicol resistance selection. In addition, they contain a gene expression cassette based on the E. coli bacteriophage T4 gene 32 promoter region and a transcription stop signal, which are separated by a segment of multiple cloning sites in both orientations. Electroporation and subsequent selection for chloramphenicol resistance was used for the introduction of the vectors in A. pleuropneumoniae and P. haemolytica. A promoterless xy/E gene from the Pseudomonas putida TOL plasmid was cloned onto pJFF224-NX. This plasmid enabled efficient expression of active catechol2,3oxygenase in A. pleuropneumoniae and P. haemolytica. It was stably maintained in A. pleuropneumoniae without antibiotic selection, showing less than 0.1% loss after 100 generations, while native RSF1010 and other RSF1010-based vectors were unstable in this host. PMID- 1448613 TI - Use of specific oligonucleotides for direct enumeration of Listeria monocytogenes in food samples by colony hybridization and rapid detection by PCR. AB - Two 18-mer oligonucleotides derived from the sequence of hly, the gene coding for listeriolysin O, were shown to be specific for Listeria monocytogenes in the genus Listeria in colony hybridization tests. The oligonucleotides did not hybridize with any of the bacterial species found in food and co-isolated with Listeria on selective media. They were used in colony hybridization tests for enumeration of L. monocytogenes present in food samples after direct plating on selective media plates. In addition, two 24-mer oligonucleotides, each including the sequence of one of the 18-mers, were successfully used for the PCR-based detection of L. monocytogenes bacilli present in food samples after 48-h enrichment period. Using this technique, as little as 10(2) bacteria per ml of enrichment broth can be detected. PMID- 1448614 TI - Cloning and characterization of a Neisseria gene homologous to hisJ and argT of Escherichia coli and Salmonella typhimurium. AB - We have isolated from a genomic library of the pathogenic Neisseriae gonorrhoeae T2 strain, a gene encoding a putative protein of 268 amino acids which exhibited significant similarity to the hisJ and argT gene products of Salmonella typhimurium and Escherichia coli, periplasmic proteins deputed to amino acid transport within the cell. The gene is transcribed as a monocistronic mRNA species of about 960 nucleotides flanked by regulatory elements for initiation and termination of transcription that are efficiently recognized in an E. coli host. PMID- 1448615 TI - Corynebacterium group D2 ("Corynebacterium urealyticum") constitutes a new genomic species. AB - Twenty-one Corynebacterium group D2 ("C. urealyticum") strains were found to constitute a tight DNA hybridization group distinct from named Corynebacterium species. The strains of Corynebacterium group D2 had cell wall component type IV, short chain mycolic acids and G+C content of DNA of 65-66 mol %. Corynebacterium group D2 constitutes a genomic species which can be identified by phenotypic tests. PMID- 1448616 TI - Detection of enterotoxigenic Escherichia coli in faecal specimens by acetylaminofluorene-labelled DNA probes. AB - The present study describes acetylaminofluorene(AAF)-modified DNA probes for the identification of heat-labile (LT) and heat-stable (porcine STp and human STh) toxins from enterotoxigenic Escherichia coli (ETEC). AAF probes were compared with established biotinylated probes and bioassays. Ultracentrifugation was not necessary in the preparation of AAF-labelled probes, and the procedures, i.e. chemical modification of probes, hybridization and immunodetection steps, were optimized to detect ETEC by colony hybridization or direct dot blot techniques. The method combines chemical labelling (covalent attachment of AAF group to guanosine is achieved by treatment of DNA with N-acetoxy-2-acetylaminofluorene) and detection of the hybridized target DNA by means of anti-AAF monoclonal antibodies and alkaline phosphatase-labelled second antibodies. PMID- 1448617 TI - DOT-ELISA for detection of phenolic glycolipid PGL-Tb1 and diacyl-trehalose antigens of Mycobacterium tuberculosis. AB - A DOT-ELISA method for detection of 2,3-diacyl-trehalose (DAT, previously referred to as SL-IV antigen) and triglycosyl phenol phthiocerol di-mycocerosate (PGL-Tb1) antigens from Mycobacterium tuberculosis is described. The method enabled the detection of both antigens in 14 clinical isolates of M. tuberculosis from different geographic origins; the presence of the glycolipids was confirmed by chemical analysis. It was therefore concluded that the synthesis of both of these compounds is characteristic of the species. PMID- 1448618 TI - Degradation of non-phenolic beta-o-4 lignin substructure model compounds by Acinetobacter sp. AB - Acinetobacter sp. utilized non-phenolic beta-o-4-model compounds, 2-methoxy-4 formylphenoxyacetic acid and veratrylglycerol-beta-guaiacyl ether (VGE) as sole carbon source. Vanillin, vanillic acid, protocatechuic acid and catechol were detected in the 2-methoxy-4-formylphenoxyacetic acid amended culture. Veratryl alcohol, veratraldehyde, veratric acid, vanillic acid, protocatechuic acid, catechol and guaiacol were identified from veratrylglycerol-beta-guaiacyl ether culture. Acinetobacter sp. produced catechol 1,2-dioxygenase and protocatechuate 3,4-dioxygenase that cleaved catechol and protocatechuic acid, respectively. PMID- 1448619 TI - Putative nickel-binding sites of microbial proteins. AB - Nickel is biologically important because of its catalytic role in the mechanisms of action of metalloenzymes, and also because of its toxic cellular effects. There exist at least 3 groups of nickel-binding proteins in microorganisms: nickel-specific transporters, accessory proteins involved in nickel incorporation and nickel-containing enzymes. The differences in their physiological functions determine the nature of the ligands and the structures of the nickel-binding sites. The homology among the accessory proteins HypB, ORF4 and UreG suggests that the mechanism of nickel incorporation into hydrogenases in Escherichia coli is the same as or similar to that into hydrogenases of Rhodobacter capsulatus and into urease of Klebsiella aerogenes. PMID- 1448620 TI - The bacterial phosphotransferase system as a potential vehicle for the entry of novel antibiotics. AB - During the past twenty-nine years, not a single class of antimicrobial agents has been discovered that has led to new approved human drugs. Despite a dramatic increase in the potency of existing classes, the need for new effective antimicrobial agents continues. The bacterial phosphotransferase system (PTS) offers the possibility of providing new opportunities for the discovery of important agents. This system offers a vehicle for entry into infecting bacteria and pathways for the initiation of metabolism of such agents. Antimicrobial agents which would use the PTS may be found which are active on both growing and sessile bacterial forms, and due to the lack of a eukaryotic PTS counterpart, such analogues may be expected to be non-toxic to the animal host. PMID- 1448621 TI - Expression of M6 protein gene of Streptococcus pyogenes in Streptococcus gordonii after chromosomal integration and transcriptional fusion. AB - The M6 protein of Streptococcus pyogenes was expressed on the cell surface and secreted in Streptococcus gordonii Challis (formerly Streptococcus sanguis) after chromosomal integration of a promoterless M6 protein gene (emm-6.1). The ermC gene, conferring resistance to erythromycin, was cloned downstream of emm-6.1, within the same ClaI fragment. The initiation codon of emm-6.1 was 19 bp downstream of a ClaI site, so that ClaI cleavage would leave the gene promoterless. The ClaI fragment containing the promoterless emm-6.1 and ermC was ligated in vitro with a ClaI digest of S. gordonii chromosomal DNA. Random chromosomal integration of the heterologous DNA was obtained by using the ligation mixture to transform the naturally competent S. gordonii Challis. Twenty eight percent of transformants selected for erythromycin resistance also expressed M6. Among the best M6 producers, 10 clones were selected for the stability of their phenotype. Nine of the 10 clones were shown to harbour one intact copy of the emm-6.1/ermC ClaI fragment integrated into the chromosome. These strains both expressed M6 protein on the surface and secreted different amounts of the molecule, since in each case the protein was produced after a transcriptional fusion of emm-6.1 with a different chromosomal promoter. A S. gordonii strain expressing large amounts of surface M6 protein, as judged by immunofluorescence and Western blot, was compared to the M- parental strain in a standard opsonophagocytosis assay. Of the isogenic pair, M6+ S. gordonii survived better in human blood and was phagocytosed at a slower rate. PMID- 1448622 TI - Conserved structural and regulatory regions in the Salmonella typhimurium btuB gene for the outer membrane vitamin B12 transport protein. AB - The Salmonella typhimurium btuB gene encodes an outer membrane protein that is necessary for the transport of vitamin B12 and the uptake of the E colicins and bacteriophage BF23. The sequence of this gene showed 87% identity of the deduced polypeptide to its Escherichia coli homolog, and its product was found to function in transport as effectively in cells of E. coli as did the native protein. The extensive sequence conservation within the first 300 transcribed nucleotides, which include the leader and early part of the coding sequence, supports the proposed role of this region in the regulation of btuB gene expression. PMID- 1448623 TI - Two unrelated alkaliphilic Bacillus species possess identical deviations in sequence from those of other prokaryotes in regions of F0 proposed to be involved in proton translocation through the ATP synthase. AB - The a and c subunits of two unrelated alkaliphilic Bacillus species contain unusual motifs in regions previously implicated by others in H(+)-coupled oxidative phosphorylation. The facultative alkaliphile B. firmus OF4 apparently does not contain genes encoding an alternative F0, supporting other evidence that a single species of proton-translocating F1F0-ATPase catalyses oxidative phosphorylation both at low and high pH. The unusual F0 sequence motifs may be part of the adaptation of the extreme alkaliphiles to growth at very high pH. PMID- 1448624 TI - Immunoaffinity purification, stabilization and comparative characterization of listeriolysin O from Listeria monocytogenes serotypes 1/2a and 4b. AB - We developed a simple and highly effective procedure for stabilizing the haemolytic activity of listeriolysin O (LLO) from Listeria monocytogenes after immunoaffinity purification. The haemolytic activity of LLO was stabilized by eluting it directly into tubes containing an alkaline buffer (5 mM lysine, 140 mM KCl, 50% ethylene glycol, pH 11.5). The purified LLO retained 100% of its haemolytic activity after 6 weeks of storage at -20 degrees C. LLO purified from a strain of L. monocytogenes serotype 1/2a (ATCC 43249) and LLO purified from a strain of L. monocytogenes serotype 4b (F 2365) isolated from a Mexican-style cheese, showed no significant differences in pH and temperature stability. When incubated in buffers at pH values from 4 to 12 at 4 degrees C and 25 degrees C, LLO from serotypes 1/2a and 4b retained maximal haemolytic activity at pH 8 after 4 h of incubation. LLO from both serotypes lost their haemolytic activity after incubation at 50 degrees C for 25 min. PMID- 1448625 TI - Typing of Listeria strains by random amplification of polymorphic DNA. AB - The polymerase chain reaction (PCR) was used to obtain randomly amplified polymorphic DNA (RAPD) profiles for typing of Listeria strains. In this procedure, whole cells were incubated in the reaction mixture. The discriminating ability of a randomly designed 10-mer primer, HLWL74, was assessed. A total of 60 collection strains of Listeria, encompassing all 7 Listeria species and all known serovars was submitted to PCR with the primer HLWL74. Upon agarose gel electrophoresis, 29 different banding profiles were reproducibly obtained. No common profiles were recorded for strains from different Listeria species. For various groups of strains sharing the same serotype (e.g. 4b, 1/2a, 1/2b), RAPD analysis could generate further subdivision. On the other hand, some strains from different serotypes produced identical RAPD profiles with the primer HLWL74. The RAPD typing method from whole cells is proposed as an attractive alternative for other Listeria typing systems, and the 10-mer HLWL74 as a primer to include in a forthcoming set of standard primers for RAPD typing of Listeria isolates. PMID- 1448626 TI - A comparative study of randomly amplified polymorphic DNA analysis and conventional phage typing for epidemiological studies of Listeria monocytogenes isolates. AB - The analysis of RAPD profiles generated by PCR with a single 10-mer, HLWL74, was compared to bacteriophage susceptibility data for epidemiological typing of Listeria monocytogenes strains. A total of 104 L. monocytogenes strains was screened, all from serogroup 1 or serotype 4b. Of these, 53 had been isolated during 6 different listeriosis outbreaks. The remaining 51 strains were chosen randomly from our collection. A total of 38 RAPD types were observed, although each epidemic group of strains isolated during one of these outbreaks displayed a specific RAPD profile. For 98% of the strains isolated during outbreaks, the correlation between RAPD typing and phage typing was complete. Only one strain, typed as epidemic by phage typing, was clearly distinguishable from the others by RAPD analysis. Among the 51 strains not related to an outbreak, 12 were linked to epidemic groups by RAPD analysis. Two of these rearrangements were supported by phage typing. The remaining 10 strains could be excluded by phage typing from any of the epidemic groups studies. Considering all 104 isolates, the decision to relate a strain to a particular epidemic group or to exclude a strain from any epidemic group was the same for 92 isolates, using either phage typing or RAPD analysis. The RAPD analysis, which is quick, simple and suited for automation, is proposed as an attractive alternative for phage typing in epidemiological studies of listeriosis. PMID- 1448628 TI - Thin-layer chromatography systems for the identification of Mycobacterium tuberculosis, M. bovis BCG, M. kansasii, M. gastri and M. marinum. AB - Knowledge of mycobacterial glycolipid antigens and the study of their specificity have resulted in their utilization as species markers. We describe a thin-layer chromatography method which could serve as a useful adjunct for the identification of Mycobacterium tuberculosis, M. bovis BCG, M. kansasii, M. gastri and M. marinum. PMID- 1448629 TI - Enzyme electrophoretic polymorphism differentiates invasive from non-invasive Chlamydia psittaci ruminant isolates. AB - A group of 24 Chlamydia psittaci strains isolated from ruminants, belonging to serotype 1 and previously classified as invasive in a mouse model of virulence, was compared to a group of 10 non-invasive strains belonging to serotype 2 by using determination of glucose-6-phosphate and L-malate dehydrogenase zymotypes resulting of the infection of cells by these strains. The serotype 1 or invasive isolates represent a homogeneous group by sharing a unique zymotype which was not observed in the non-invasive strains. On the contrary, the serotype 2 or non invasive isolates constitute a heterogeneous group in generating 2 different zymotypes. Zymotyping clearly distinguishes the ruminant strains from an avian C. psittaci and two C. trachomatis isolates studied for comparison. Our results suggest the usefulness of the studied molecular approach for chlamydiae typing. Furthermore, it can be used as marker of virulence within the C. psittaci strains isolated from ruminants. PMID- 1448627 TI - A rapid and sensitive method for the identification of Brucella species with a monoclonal antibody. AB - A coagglutination test using monoclonal antibody BmE10-5 with specificity for the M antigen of Brucella melitensis 16M has been developed for the rapid identification of the smooth Brucella species. All reference strains of several biovars of B. melitensis, B. abortus, B. suis and B. neotomae tested were positive in this assay. No significant differences in reaction intensity were observed in relation to the different distribution of the A and M antigens among the Brucella serovars analysed. Conversely, rough Brucella species, with the exception of B. abortus 45/20, were negative in the assay. Among the different organisms tested not belonging to the genus Brucella, serovar O9 of Yersinia enterocolitica was the only one that gave a weak positive reaction of coagglutination. Thus, in view of its rapidity, simplicity, specificity and low costs, this technique could be highly useful for rapid identification of smooth Brucella strains in diagnostic laboratories. PMID- 1448630 TI - The antigenic relationship between Candida tropicalis and Escherichia coli (O 75, O 163) and Salmonella serotype Aberdeen O antigens. PMID- 1448631 TI - [What is your diagnosis? Varicella]. PMID- 1448632 TI - [chronic headaches caused by drug abuse: danger for patients with migraine]. PMID- 1448633 TI - [Pathology of myxoid mitral valve degeneration: literature review and personal results]. AB - Mitral prolapse is a parachute-like protrusion of the value into the left atrium. Almost always a myxoid degeneration of the valve is the base of such a prolapse. Myxoid degeneration is understood as dissolution of the collagenous fibrous layer and its replacement by acid glucosaminoglycans. An alteration of collagen is suspected as primary defect in this sometimes also inherited disorder. The electron microscope reveals fragmentation of collagen fibrils and elastic fibers and, within the myxoid material, free lysosomes, so called "matrix-vesicles". An isolated disturbance of collagen types I and III could not be detected by immunohistochemistry. Studies could also to date not demonstrate mutations in the genes coding for collagens. PMID- 1448634 TI - [Rickets due to vitamin D deficiency--a reminder]. AB - Vitamin D deficiency, because of prophylactic supplementation, has become a rare disorder in Switzerland and therefore is usually not considered in the clinical routine. In the few cases we could diagnose, the affected children either have been of East-Mediterranean origin with insufficient nutrition and vitamin supplementation, or were raised in families who, for philosophical or other reasons, refuse any "non-biological" measure including vitamin supplementation. For the orthopedic surgeon the challenging task is to screen out of the many children presented with physiologic gait "disturbance", bow-legs or flat feet the few children with true disorders. An important point is the history of vitamin D prophylaxis; in selected cases X-ray and laboratory findings are indicated. Finally the response to the treatment with vitamin D will confirm the diagnosis of rickets due to vitamin D deficiency. PMID- 1448635 TI - [Advantages of 24-hour ambulatory blood pressure monitoring for the assessment of dose-effect relations and dose-equivalency]. AB - Because of the high variability of blood-pressure, clinical studies using casual measurements require rather large numbers of patients for assessment of pharmacologic efficacy. By the use of blood-pressure monitoring over 24 hours this number can be dramatically reduced. Additional benefits are the precise determination of dose-effect relationships and the more accurate estimate of the response-rate. Comparing two retarded galenic forms of Verapamil we show that even dose-equivalence can be studied with this type of blood-pressure recording. PMID- 1448636 TI - [Clinical-pharmacological case report: drug-induced inappropriate ADH secretion]. AB - The syndrome of inadequate secretion of antidiuretic hormone (SIADH) following treatment with a tricyclic antidepressant is demonstrated using the example of a 70 year-old man admitted for weakness and cognitive disturbances. Because of incontinence he had been periodically treated since 1989 with imipramine (Tofranil) by his family doctor. On admission he was seriously hyponatriemic and had low plasmatic osmolality, significantly lower than urinary osmolality. Creatinine, urea and uric acid in serum were also below normal values. Like other drugs tricyclic antidepressants can rarely induce an increased release of ADH by direct hypothalamic stimuli. In this patient imipramine was terminated and within a few days of reduced fluid intake and substitution of sodium a sustained clinical improvement and normalisation of laboratory parameters was noted. The patient was discharged to his home after three weeks. PMID- 1448637 TI - [A case from practice (257). Cryptococcus meningitis in AIDS (Group IVc1, Center for Disease Control)]. PMID- 1448638 TI - [What is your roentgen diagnosis? Aphthous esophagitis?]. PMID- 1448639 TI - [Diagnosis of neurological symptoms of psychogenic origin]. AB - The principles of neurological examination of patients in which psychogenic disturbances are suspected are first described. After mentioning the frequency of this type of disturbances in the medical literature, some of the most characteristic and most frequent psychogenic disturbances in neurology are described: cranial nerve symptoms, sensory disturbances as well as psychogenic paralysis including paraplegia and psychogenic disturbances of gait. A chapter is dedicated to psychogenic disturbances of consciousness and to psychogenic attacks mimicking epilepsy. Finally a description is given of those organic neurological diseases in which in our experience the erroneous diagnosis of psychogenic disturbances is most frequently made. Some recommendations, how to behave in the presence of a patient with psychogenic neurological symptoms is added. PMID- 1448640 TI - ["Psychogenic" bulbar paralysis]. AB - This 58-year-old female presented with a history of difficulties in swallowing for 30 years. No diagnosis was made in spite of repeated investigations including barium-contrast radiography. A probative strumectomy and psychotherapy were unsuccessful. After an episode of major depression the swallowing disturbances increased. In addition the patient complained of mastication difficulties and was dysarthric. Finally, neurological examination and neurophysiological studies established the diagnosis of progressive bulbar palsy. PMID- 1448641 TI - [Autoimmune paraneoplastic neurological syndromes]. AB - Paraneoplastic neurological syndromes are well established causes of neurological dysfunction in cancer patients. Recently an auto-immune origin has been found for the Lambert-Eaton myasthenic syndrome, the subacute sensory neuronopathy of Denny Brown, the paraneoplastic cerebellar degeneration, the paraneoplastic opsoclonus myoclonus as well as a few other minor syndromes. Indeed patients suffering from these diseases have been found to produce antibodies directed against the central nervous system. These antibodies can be detected as much as a year before the cancer is found and they are therefore interesting for neurological and oncologic diagnosis. PMID- 1448642 TI - [Current developments in the long-term therapy of Parkinson syndrome]. AB - In the course of long-term treatment of Parkinson's disease many problems, which cannot yet be satisfactorily solved, arise with time in a large number of patients. This overview describes some strategies which are used nowadays to tackle these problems. Special attention is drawn to the treatment of painful dystonias and off-periods with apomorphine. PMID- 1448644 TI - [HIV transmission by saliva?]. PMID- 1448643 TI - [Bell's palsy--a field of controversies. I. Etiology and pathogenesis--diagnostic delimitation--prognosis]. AB - Facial paresis as a sign or symptom is caused by a number of different conditions. Although being the most common type of facial paresis, Bell's palsy represents a diagnosis of exclusion characterized by an acute, unilateral peripheral facial palsy of unknown etiology. Clinical features and laboratory findings are considered with regard to their diagnostic as well as prognostic significance. PMID- 1448645 TI - The phenotypic expression of different mutations in transmissible human spongiform encephalopathy. AB - Clinical, pathological, and experimental transmission characteristics are reviewed for each of the known mutations in the amyloid precursor gene (PRNP) associated with familial spongiform encephalopathies. All mutation groups show an earlier age at onset and longer duration of illness than sporadic disease, and more or less distinctive patterns of illness can be recognized for each mutation, although much variability may occur even among affected members of the same family. Experimental transmission of disease has been accomplished for most of the mutations, with shortened incubation periods in the inoculated animals that parallel the earlier age at onset of human illness in these cases, implying a shortened pre-clinical phase of disease rather than an earlier 'infecting event'. Mutations thus not only predispose to spongiform encephalopathy, but also accelerate its pathogenetic tempo and influence its phenotypic expression. PMID- 1448646 TI - [Creutzfeldt-Jakob disease in 4 children treated with growth hormone]. AB - Creutzfeldt-Jakob disease was diagnosed in four growth hormone recipients at the age of 10, 11, 18 and 19 years. To our knowledge, the two first cases are the first instances of Creutzfeldt-Jakob disease recorded in children. Three of them were still being treated with synthetic hormone at the onset of the disease. Neurological disorders: ataxia and diplopia, appeared first, dementia and myoclonus appeared later. Eighteen cases of Creutzfeldt-Jakob disease in growth hormone recipients are now recorded, and the present risk of Creutzfeldt-Jakob disease in pituitary growth recipients is estimated to be 1/300. Because of the long incubation period, new cases are to be feared. Other causes of iatrogenic Creutzfeldt-Jakob disease are reviewed. These facts incite to consider carefully using products of human origin in human therapy. The interactions between growth hormone, prion and host's genomic make-up are still not clear. PMID- 1448647 TI - [Gerstmann-Straussler-Scheinker disease. Pathologal and genetic study]. AB - Gerstmann-Straussler-Scheinker's disease is a familial spongiform encephalopathy whose pathological hallmark is the existence--especially in the cerebellum--of numerous amyloid plaques. We report here the third clinicopathological case in a French family. Brain tissue from one of its members--initially described as familial Creutzfeldt-Jakob's disease--has been reported as successfully inoculated to monkeys. We present the currently accumulating data favouring the hypothesis of a common etiology for familial Creutzfeldt-Jakob's disease and Gerstmann-Straussler-Scheinker's disease. The familial characteristics, resulting in different durations of incubation and evolution, could lead to different clinical and histological expressions. PMID- 1448648 TI - [Ambulatory autonomy and visual motion perception in a case of almost total cortical blindness]. AB - A 37-year-old man experienced cortical blindness following a bilateral stroke in the territory of the posterior cerebral arteries. Four years later, the measurement of visual field defects (Goldmann perimeter) showed persistence of bilateral blindness with a 2-degree preservation of macular vision and a perifoveal sparing between 10 to 30 degrees of eccentricity in the left inferior quadrant. Despite this visual impairment, the subject was able to perform visually-guided locomotion. Moreover he consciously perceived visual motion in the blind parts of his visual field. CT and MRI showed a lesion involving most of the striated cortex. The visual cortex located in the internal occipito-parital regions was relatively spared. The contribution of this structure to extra striated vision of motion is discussed. PMID- 1448649 TI - [Stiff-Man syndrome with late onset]. AB - We report a case of Stiff-Man syndrome according to Gordon, Januszko and Kaufman's criteria. Onset at age 76, association with insomnia and a rapid course leading to death within 2 years were the characteristic features. CSF data, electromyographic and immunological findings suggest abnormalities of catecholaminergic and GABA ergic systems, with release of segmental or suprasegmental inhibitory influence. The presence of antibodies against glutamic acid decarboxylase, considered a useful marker of this syndrome, raises the possibility of an autoimmune pathogenesis. PMID- 1448650 TI - [Post-poliomyelitis syndrome: 29 cases]. AB - The post-polio syndrome refers to new neuromuscular symptoms developed by some patients many years after recovery from acute poliomyelitis. Several groups were separated: musculo-skeletal symptoms (different from a new spinal cord disease), infraclinical signs (EMG), post-polio muscular atrophy (new lower motor neuron objective signs) with several subgroups: cramps and fasciculations, benign focal weakness and atrophy (in previously affected muscles or in unaffected muscles), progressive spinal muscular atrophy. The following examination were performed in some cases, but not all, in this retrospective study: muscle CT scan, conventional electromyography (EMG), quantifying-EMG, macro-EMG and single-fiber EMG. The serum titers of neutralising antibodies to polio virus type 1, type 2 and type 3 were negative. No oligoclonal bands were found in the CSF from 6 patients screened by electrophoresis immunoelectrophoresis. Serum creatine kinase or aldolase was high in 6 patients. The same unusual features in this syndrome were observed on muscle biopsies: muscular hypertrophy and interstitial eosinophils; two patients had rimmed vacuoles in the muscle fibers. PMID- 1448651 TI - [Suprascapular nerve entrapment at the spinoglenoid notch]. AB - The suprascapular nerve passes through the spinoglenoid notch with a risk of entrapment. This results in distal nerve lesion characterized by isolated paralysis of the infraspinatus muscle and, most often, by shoulder pain. We report 7 clinical and electromyographical cases of pure infraspinatus muscle paralysis. The value of the electrodiagnosis, which demonstrated prolonged suprascapular distal nerve latencies (over 5 milliseconds) in the infraspinatus muscle affected while latencies were normal in the supraspinatus muscle, is emphasized. Mechanical factors were associated with paralysis in 5 cases. Compressive synovial cysts were found in 2 patients operated upon. Surgical enlargement of the spinoglenoid notch regularly and rapidly relieves pain and sometimes helps in recovery of the infraspinatus muscle. PMID- 1448652 TI - [Paralytic pontine exotropia disclosing endocarditis]. AB - A case of bacterial endocarditis complicated by paralytic pontine exotropia is reported. Magnetic resonance imaging clearly showed a rostral lesion of the paramedial pontine reticular formation and the medial longitudinal fasciculus. The occurrence of paralytic pontine exotropia is suggestive of ischaemia, and patients with this so-called "one-and-a-half syndrome" associated with signs of infection should be investigated for endocarditis. PMID- 1448653 TI - [Hashimoto's encephalopathy: toxic or autoimmune mechanism?]. AB - A 36-year-old woman presented with partial complex status epilepticus. Magnetic resonance imaging with T2-weighted sequences showed a high-intensity signal in the left posterior frontal area. Hashimoto's thyroiditis was then discovered. The disappearance of the high-intensity signal after corticosteroid therapy was suggestive of an autoimmune mechanism. However, improvement could be obtained only with a hormonal treatment, which supports the hypothesis of a pathogenetic role of the Tyrosine-Releasing Hormone (TRH). PMID- 1448654 TI - [A progressive case of ataxia in a family of Huntington's chorea]. AB - One case of ataxic, pyramidal and demential syndrome associated with retinitis pigmentosa occurred in a family with Huntington's disease (36 patients among 7 generations). The disease started at 15 years of age. Ataxia was transiently attenuated by isoniazid. The patient died of the disease at 26 years of age. PMID- 1448655 TI - [Dementia disclosing primary Gougerot-Sjogren syndrome]. AB - Two cases of primary Sjogren's syndrome revealed by dementia are reported. The patients had progressive or subacute memory dysfunction and psychiatric disorders with depression and delirium. The diagnosis of Sjogren's syndrome was established by biopsy of the minor salivary glands. Both patients were treated with corticosteroids. The neuropsychiatric symptoms improved dramatically in one case and remained unchanged in the other case. Dementia in Sjogren's syndrome seems to be without aphasia, apraxia or agnosia, and associated with psychiatric features, particularly depressive symptoms, thus including some characteristics of subcortical dementia. Diagnosis may be difficult because, as shown in our cases, symptoms of ocular and buccal dryness can be absent. Salivary gland biopsy can be useful in the evaluation of patients with dementia of undetermined etiology. PMID- 1448656 TI - [Chorea disclosing polycythemia and renal adenocarcinoma]. AB - A 79-year-old woman had chorea complicating polycythaemia. The polycythaemia and the chorea disappeared after surgical removal of a renal carcinoma. The literature on polycythaemic chorea is reviewed and its pathophysiology discussed. PMID- 1448657 TI - [Magnetic resonance imaging in lupic chorea]. AB - A case of disseminated lupus erythematosus with chorea is reported. CT was normal. Magnetic resonance imaging showed multiple focal lesions on T2-weighted sequences, predominating in the periventricular white matter. This MRI pattern did not change in a second MRI investigation, 7 months later. The contribution of MRI to our understanding of the neurolupus pathophysiology is discussed. PMID- 1448658 TI - Cell kinetics of glial tumors. AB - The development of monoclonal antibodies against bromodeoxyuridine (BUdR) has made it possible to study the cell kinetics of individual brain tumors more extensively and more rapidly than previously possible. Over the past several years, we have performed in situ labeling studies of 502 neuroectodermal tumors with BUdR. The results have shown that the BUdR labeling index (LI), or percentage of cells in DNA synthesis, is generally higher in malignant gliomas; that histologically similar tumors may have different proliferative potentials, demonstrated by differences in the BUdR LIs; and that a higher LI indicates a higher proliferative potential as well as a shorter time to recurrence and duration of survival. Double-labeling studies with BUdR and iododeoxyuridine, performed to analyze the cell cycle progression in 29 gliomas, revealed that S phase duration (Ts) was fairly uniform (mean +/- SD: 8.9 +/- 2.0 hours) regardless of the differences in the LIs. Nevertheless, the potential doubling time (the time for a tumor cell population to double in the absence of cell loss) varied from 2 days to over a month, being very short for tumors with a high LI, and correlated with the BUdR LIs (Tp = 17.8/LI0.77; r = 0.95). The cell cycle time calculated for gliomas with LIs of 1-20% was 1-2 days. These parameters are useful in determining the dose, duration, and interval of chemotherapy and in evaluating the effectiveness of treatment. Thus, cell kinetics studies not only elucidate the growth characteristics of individual gliomas but may also benefit to patients by providing a more precise prognosis and may be considered in the selection of treatment modalities. PMID- 1448659 TI - Oncogenes and glial tumors. AB - Results of numerous studies indicate that both activation of dominant oncogenes and inactivation of tumor suppressor genes play important roles in the genesis and progression of human gliomas. Activation of the epidermal growth factor receptor (erbB1 oncogene) as the result of gene amplification or rearrangement is the best established example of a dominant oncogene involved in glioma development. There is also suggestive evidence for activation of the ros oncogene in gliomas, and activation of a variety of other dominant oncogenes may be operative in individual tumors. Deletion studies suggest that inactivation of tumor suppressor genes on chromosomes 17p (probably the p53 gene), 10, 9p and 22 also play roles in genesis and progression of human gliomas. Additional work remains to be done to identify other dominant oncogenes and tumor suppressor genes involved in gliomas, and to determine how these various factors interact to cause disease. PMID- 1448660 TI - [Chromosome abnormalities and adenine metabolism in human glial tumors]. AB - Most chromosome aberrations in gliomas are numerical, resulting in either gains or deficiencies of whole chromosomes. In tumors of low malignancy, the karyotype is frequently normal or exhibits a loss of sex chromosome and a gain of chromosome 7. These two anomalies may not be directly related to malignancy. In the highly malignant cases, the two most frequent aberrations are the gain of chromosome 7 and the loss of chromosome 10, other anomalies such as losses or deletions of chromosomes, 9, 22, 6, 13 and 14 being detected at various frequencies. Several of these chromosomes carry important genes of adenine metabolism: AK1 and AK3 (adenylate kinase) and MTAP (methylthioadenosine phosphorylase) for chromosome 9; ADK (adenosine kinase) and mitochondrial ATPase for chromosome 10; ADSL (adenylosuccinate lyase) for chromosome 22, NP (nucleoside phosphorylase) for chromosome 14. We performed the corresponding assays of enzyme activity on both fresh tumors and tumors grafted on nude mice, which showed that these enzymes had a relatively low activity although the tumors were proliferating. However, chromosome losses do not seem to directly cause the metabolic alterations by gene dosage effect. Interestingly, chromosome 10, frequently deficient, also carries genes of importance for glycolysis (hexokinase) and glutamate metabolism (glutamate dehydrogenase and glutamate oxaloacetate transaminase). The deficiency for these genes could be taken into account for a better type of chemotherapy by antimetabolics. PMID- 1448661 TI - [Contribution of nucleolar organizers staining to the prognostic evaluation of meningioma]. AB - Meningioma is often regarded as a benign tumour. It is easy to diagnose, but its prognosis is difficult to determine. Recurrences are numerous and occur at different periods of time. Various predictability factors have been studied, including Nucleolar Organizers Regions (NORs) staining. This technique is easy to perform and enables retrospective studies to be carried out. Comparisons of staining indices with the histoprognostic grades established by Zulch, and correlations between these indices, as well as with the time elapsed before a recurrence occurred, showed that NORs staining can be useful to determine the prognosis. In this retrospective study 69 cases were reviewed. The meningiomas had been removed surgically between January 1979 and December 1991. The clinical follow-up, which lasted from 11 months (for the most recent cases) to 132 months (for the earlier cases), shows that the staining index reaches a critical value beyond which an early recurrence might be expected. PMID- 1448662 TI - Chemotherapy of malignant gliomas: studies of the BTCG. AB - Phase III Trial 8,301 tested the efficacy and safety of intraarterial (IA) BCNU for the treatment of newly resected malignant glioma, comparing IA BCNU vs intravenous (IV) BCNU (200 mg/m2 q 8 wks), each regimen without or with IV 5-FU (1 g/m2/d x 3 two wks after BCNU). All patients also received radiation therapy. 505 patients entered the study; 448 were in the Valid Study Group (VSG). Excluding 190 patients who for medical reasons were not eligible for IA BCNU, 315 patients were randomized between IA (167) and IV (148) BCNU. Actuarial analysis (log-rank) demonstrated worse survival for the IA group (p = 0.002). Serious toxicity was observed in the IA group; 16 patients (9.5%) developed irreversible encephalopathy with CT evidence of cerebral edema, and 26 patients developed visual loss ipsilateral to the infused carotid artery. 5-FU did not influence survival. Survival between the IV and the IA BCNU patients with glioblastoma multiforme did not differ, but was worse for IA BCNU patients with anaplastic astrocytoma than for IV BCNU (p = 0.002). Neuropathologically, IA BCNU produced white matter necrosis. IA BCNU is neither safe nor effective. Phase II Trial 8420, compared IA cisplatin, 60 mg/m2 every 4 wks, vs IV PCNU, 100 mg/m2 q 8 wks; 311 patients were randomized. Preliminary results have been presented. Severe encephalopathy occurred in only 1.5% of patients receiving IA cisplatin. The median survival of the IV PCNU patients was 11.8 months; that of the IA cisplatin patients was 9.4 months, not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448663 TI - [Chemotherapy of malignant glioma. Results of studies of the EORTC group of brain tumors]. AB - The EORTC Brain Tumor Group has conducted 5 randomized and prospective phase-III trials in adults with supratentorial malignant gliomas testing the following adjuvant treatments: 1) CCNU 130 mg/m2, q.6 weeks (trial 26741); 2) VM-26 100 mg/m2 on day 1, plus CCNU 130 mg/m2 on day 2, q.6 weeks, given either during radiation therapy (trial 26751) or during 12 weeks prior to irradiation (trial 26841); 3) Misonidazole 12 mg/m2 total dose in 9 fractions (trial 26801); 4) Cisplatin 60 mg/m2 on days 1, 8, 15 and 21 of radiation therapy (trial 26851). None of these treatments did prolong significantly the survival nor the time to recurrence. The most powerful prognostic factors found in every trial were tumor pathology, patients' age and neurological status. Objective remission lasting 6 to 9 months, defined as a clinical improvement persisting after discontinuation of corticosteroids, was observed with CCNU, VM26 plus CCNU or HeCNU in approximately 20% of the patients, while 30% stabilized on HeCNU. The activity of procarbazine, AZQ or DDMP used as single agents was much lower. PMID- 1448664 TI - [Treatment of supratentorial glioma in adults by intra-arterial HECNU. Experience of the Pitie-Salpetriere group]. AB - Between 1984 and 1988, patients suffering from malignant gliomas received intraarterial chemotherapy with HECNU (IAC). Three groups were identified. Group 1 consisted of 56 patients previously treated with surgery and radiation therapy (RT), who received IAC at recurrence. Group 2 consisted of 46 patients with unresectable tumors, and group 3 of 40 patients who had their tumor surgically removed. In groups 2 and 3, three courses of IAC were administered prior to conventional RT (50-54 Gy). Immediate tolerance was good but delayed ocular and cerebral toxicity occurred in 14% and 11% of cases, respectively. A better therapeutic response was observed with anaplastic gliomas than with glioblastomas (GBM). For anaplastic gliomas, median survivals (MS) were 18 months (group 1), 24 months (group 2) and 30 months (group 3). For GBM, MS were 4.5, 7.5 and 10.5 months in groups 1, 2 and 3, respectively. IAC does not seem to improve the prognosis of GBM. PMID- 1448665 TI - Interstitial irradiation of malignant gliomas. AB - Beginning in 1986, using software to optimize radiation dosimetry, we have stereotactically placed removable catheters containing high activity I-125 sources into malignant gliomas in 56 patients. There were 32 men and 24 women, age 7 to 73. Forty-four had glioblastoma multiforme, and 12 anaplastic astrocytoma. Mean Karnofsky performance score was 75, range 50-100. Twenty patients (all with glioblastoma) were implanted after resection before further therapy, and 36 were implanted at recurrence following resection, external irradiation and chemotherapy. Six thousand cGy was delivered to the enhancing tumor contour on CT scan. Mean dose rate was 37 cGy/hr. Mean tumor volume was 41 cc, range 5-187 cc. Mean volume of brain that received 60 cGy was 67 cc, range 11 184 cc. Of 20 patients treated after resection alone, 8 are alive, 3-43 months after implantation; median survival is 22 months. Of 36 patients treated at recurrence, 14 are alive, 0-19 months after implantation; median survival is 10 months. The most common side effect of the procedure, which occurred in five patients, was catheter misplacement. Twenty-four patients (43%) required 27 reoperations, 1-25 months after implantation. In 25 pathologic specimens available for review, microscopic tumor foci with substantial radiation necrosis were found in 18, radiation necrosis only was noted in 5, and glioma alone was seen in 2. PMID- 1448666 TI - The cellular immunotherapy of primary brain tumors. AB - The use of adjuvant immunotherapy for the treatment of primary malignant brain tumors dates to studies performed in the 1960's and 1970's using non-specific immune stimulators. Although the theoretical designs have remained similar, recent advances in molecular biotechnology have produced a new group of recombinant cytokines, spawning a new generation of immunotherapy-based clinical trials. In contrast to other published Phase I/II studies, we have had highly encouraging preliminary results using lymphokine-activated killer (LAK) cells and recombinant human Interleukin-2 (rIL-2; Cetus, Emeryville, CA), when the patients' use of corticosteroids could be restricted while on study. Patients with recurrent grade 3/3 glioma received multiple cycles of autologous LAK cells and rIL-2, post-operatively, via an Ommaya reservoir implanted into the tumor cavity following re-operation. The overall median survival for 13 patients with grade 3/3 glioma has not yet been reached at 55 weeks following second surgery, [mean +/- SEM, 64.7 +/- 10.5 weeks], with 5 patients still alive. Three patients have had partial responses (PR) demonstrated by CT scanning. In addition, one patient with grade 2/3 glioma has had a complete response (CR), with the disappearance of all residual CT-documented enhancement and mass effect. PMID- 1448667 TI - Childhood medulloblastoma. AB - The progress that has been made in the treatment of the patient with medulloblastoma is gratifying. Survival for those who fall into the lower risk category probably exceeds 75%. For this degree of success, however, patients and their families have had to pay a price in terms of suffering the deleterious late effects of treatment. With sophisticated neuroimaging techniques diagnoses are now being made in a timely fashion and surgical mortality has been reduced to almost zero in most major medical centers. Radiation therapy and chemotherapy regimens have been increasingly successful, and further refinements of treatment are to be expected with the completion of randomized cooperative group trials. It is time to focus on means of achieving similar, or even better results, with reduced doses of neuraxis radiation, whenever possible, especially in the younger patient. PMID- 1448668 TI - Management of brain metastases. AB - Brain metastases are common and often occur in patients whose systemic cancer is quiescent. When brain metastases occur, they considerably decrease the quality of life in patients who otherwise might be functional. An early diagnosis and vigorous treatment of the brain metastasis, while only rarely curative, may lead to a useful remission of the brain symptoms and may both enhance the quality of the patient's life and prolong survival. Patients with known cancer and neurological symptoms should all undergo appropriate diagnostic tests which include either CT scan or magnetic resonance imaging and, if a lesion is found and a definitive diagnosis can not be established, biopsy. Single or solitary brain metastases in patients with good systemic performance status should be strongly considered for surgical extirpation which will both make the diagnosis and deliver definitive treatment to the lesion. Patients with poor systemic performance status and/or multiple brain metastases are candidates for whole brain radiation therapy. Whole brain radiation therapy is also indicated in patients after successful surgical extirpation of a single metastasis. The role of focal radiation therapy and chemotherapy in the treatment of brain metastases is still being evaluated. Preliminary evidence suggests that focal radiation therapy is probably useful for the treatment of relapsed metastases and that chemotherapy may be useful in the primary treatment of small or asymptomatic brain metastases. Appropriate use of therapeutic modalities directed at brain tumors will ameliorate symptoms in most patients and usually increase survival and enhance the quality of the patient's life. PMID- 1448669 TI - [Inoperable brain metastases from bronchogenic cancers. Value of combined chemotherapy with cisplatin and 5 fluorouracil]. AB - We report the results of a combined of chemotherapy with CDDP and 5 FU repeated every 3 weeks in sixteen men (age range 31-73 years) with brain metastases. CT was performed after 2, 4 and 6 cycles to assess efficiency. Response was considered complete when no lesion was found on the CT scan and partial when the lesion shrunk to least half its the total volume. After two cycles, the response rate was 8/16 (50%). Treatment toxicity was mild with only one case of severe but reversible myelotoxicity (grade III). CDDP and 5 FU combined chemotherapy can be a useful treatment for brain metastasis of lung carcinoma. PMID- 1448670 TI - Clinical and pathological advances on central nervous system paraneoplastic syndromes. AB - In the last decade, several features have improved our knowledge of CNS paraneoplastic syndromes. Patients with paraneoplastic cerebellar degeneration (PCD) and breast or ovarian cancer, but not with other tumors, harbor an antibody against Purkinje cells (called anti-Yo). Clinical features of anti-Yo positive and negative PCD are similar but the latter may have a less progressive clinical course with occasional remissions. In addition to the association of opsoclonus with neuroblastoma, this syndrome has been identified in patients with breast or small-cell lung cancer (SCLC). Patients with opsoclonus and breast cancer have an antineuronal antibody (called anti-Ri) not present if opsoclonus is associated with SCLC or neuroblastoma. Paraneoplastic encephalomyelitis (PEM) is almost always associated with SCLC. Most patients present with sensory neuronopathy, limbic or brainstem encephalitis but involvement of multiple levels is usual. An antibody (called anti-Hu) against neuronal nuclear antigens is present in patients with PEM and SCLC. Autopsy studies demonstrate deposits of anti-Hu specific IgG in the neurons and a predominance of T cells in the inflammatory infiltrates. Treatment of the tumor and immunosuppressors are effective in opsoclonus whereas patients with PCD or PEM with circulating antibodies do not improve. PMID- 1448671 TI - [Lambert-Eaton syndrome: clinical and electrophysiological study of 18 cases associated with lung cancer]. AB - The clinical and electrophysiological data of 18 consecutive adult patients with paraneoplastic Lambert-Eaton myasthenic syndrome (LMES) have been reviewed. The cancer associated with LEMS was small-cell lung carcinoma (SCLC) in 15 cases and epidermoid lung carcinoma in 3 cases. The main clinical neurological features were proximal lower limb weakness (100%), depressed tendon reflexes (94%) and dryness of the mouth (66%). The results of repetitive nerve stimulation (RNS) were not statistically different in the paraneoplastic LEMS group and in a group of 6 LMS patients in whom no carcinoma had been detected. Low-amplitude compound muscle action potential (CMAP) was present in all cases; decremental response at low stimulation rates was present in 13/15 cases. An abnormal incremental response at high stimulation rates was observed in all cases. A close correlation between CMAP amplitude and clinical condition was found in 4 cases during the long-term follow-up. In one patient the RNS electrical pattern could be misinterpreted as myasthenia gravis in only one muscle tested. We underline the usefulness of a 50 Hz stimulation during 4 seconds to establish the diagnosis unequivocally, and that of post-exercise facilitation in routine detection among an SCLC population. Our results suggest that CAMP amplitude and RNS test could be used to evaluate the short-term improvement of LMS under treatment and, in some cases, for the long-term follow-up. The infraclinical axonal neuropathy detected in 8 patients probably was another associated autoimmune paraneoplastic complication. PMID- 1448672 TI - NARES: a model of inflammation caused by activated eosinophils? AB - Twenty patients were selected on the basis of perennial rhinitis, the absence of allergy and with an eosinophil count higher than 20% of total leucocytes in nasal secretions (NARES). Nasal endoscopy with biopsies from the middle turbinate and sinus CT were performed. Biopsies were processed for histological examination and for immunofluorescence. The clinical progress during treatment was scrutinized. An acute congestive aspect of the nasal mucosa was noted in 4 cases, and micropolyposis in 9 cases. Sinus CT showed opacity of the ethmoidal cells in 87% of cases (maxillary sinuses: 75%; frontal sinus: 46%; sphenoidal sinus: 31%). An eosinophilic infiltrate of the nasal mucosa was constituted in 9 cases: In 6 cases, the cells expressed the Fc epsilon RII receptor, recognized by the monoclonal antibody Bb10. Anti-H1 drugs usually failed to result in a clinical improvement and local eosinophilia was not changed. Local corticoids were more effective but not sufficient in some cases, so that oral corticotherapy was needed. Ethmoidectomy was performed in three cases. NARES seems to evolve in three stages: (1) migration of eosinophils from the vessels to the secretions; (2) retention of eosinophils in the mucosa which might be linked to activation of unknown origin; (3) nasal polyposis. Numerous interactions between irritation of the epithelium, release of substance P, and eosinophils, lead to the hypothesis of a neurogenic origin of NARES. PMID- 1448673 TI - Eosinophilia in nasal secretions compared to skin prick test and nasal challenge test in the diagnosis of nasal allergy. AB - This study was aimed to assess the usefulness of eosinophilia measurements in nasal smears (ENS) in the diagnosis of nasal allergy. Nasal smears were taken from 84 patients with histories suggestive of allergic rhinitis. The smears were stained by the Giemsa method and examined by light microscopy. Positive results were demonstrated in 69.2% of the samples. All the 84 patients also had a skin prick test (SPT); the perceniitage of correct correlation between ENS and SPT was 71.4%. Forty-two patients underwent nasal challenge test (NCT) and the percentage of correct correlation between ENS and NCT was 69%. Nine patients had negative SPT, but positive ENS. All were nasally challenged with 4 proving positive. This leaves 5 individuals (5.9% of the 84 studied) in the non-allergic rhinitis with eosinophilia category. Based on these findings, it is suggested that the assessment of eosinophils in nasal smears should be given more relevance and be more commonly used in the diagnosis of nasal allergy. PMID- 1448674 TI - Rhinomanometric detection rate of rhinoscopically-assessed septal deviations. AB - Normal values for the flow at a transnasal pressure of 150 Pa were established with active anterior rhinomanometry (with decongestion) in a group of 33 normal subjects. These values were used to detect abnormalities in a group of 193 patients whose septum anatomy had been evaluated with rhinoscopy. About 25% of the rhinoscopically normal patients were found to have significantly low ("abnormal") flow values on one side. The same was true for patients with a small septal deviation restricted to one anatomical area. An abnormal flow was measured in about 35% of the patients with a moderate (restricted) septal deviation. In the patients whose septal deviation was not restricted to one anatomical area, about 45% had an abnormal flow. The highest detection rate was about 80% in patients with major deviations in the region of the vestibule and the valve. Such deviations were found only in a minority of the patients with complaints of nasal obstruction, which limits the importance of rhinomanometric evaluation in clinical practice. PMID- 1448675 TI - Antroconchopexy for surgical treatment of perennial rhinitis. AB - We report on a rhinomanometric assessment of eleven patients undergoing antroconchopexy for relief of a "stuffy" nose. This little-known procedure involves the lateralization of the inferior turbinate through a large intranasal antrostomy. Our results demonstrate a significant improvement in postoperative inspiratory and expiratory nasal resistance. There was also a significant improvement in patient's scoring for nasal obstruction. Finer points of the surgical technique, and indications for the procedure are discussed. PMID- 1448676 TI - The nasal provocation test in the diagnosis of allergic rhinitis. Behaviour and dynamics of nasal flow during the test. AB - We analyzed the value of the (n) coefficient of nasal flow in the formula of nasal resistances in order to: (1) calculate nasal flow during the course of the nasal provocation test, and (2) try to find out whether nasal flow maintains the same characteristics during the test. Our results show that values vary between 1.6589 and 1.8801, with a weighted mean of 1.7645--suggesting that the flow is of a mixed character--without significant differences during the course of the test. At the same time we carried out an analysis of the dynamics of nasal flow during nasal provocation. PMID- 1448677 TI - Respiratory tubes with nasal packings following septorhinoplasty. AB - The use of packings following septorhinoplasty is a matter of controversy. The recommendations go from gluing with fibrin glue only, if anything at all, over quilting stitches, perhaps in combination with silastic or teflon sheats or plates or these sheats alone, to the employment of various more substantial materials and in from 1 to even 14 days postoperatively. If long-term nasal packing is chosen following consideration of primary healing, patients will experience discomfort of mouth-breathing, but pressure in the ears, too. Therefore, our department has used respiratory tubes simultaneously with packings since 1971. In this study, 47 patients who underwent septo- and/or rhinoplasty were treated by nasal packings 6 days postoperatively. All patients were treated by silicone respiratory tubes, one group in all 6 days, one in 4 days only. Self assessment as far as some typical complaints is concerned was carried out as well as tympanometry. There were statistically significant less complaints of pressure in the ears when tubes were used, and the period with tubes was significantly preferred to the period without. A low pressure in the middle ears was seen in many patients. The normalization was occurring significantly sooner with tubes. At the same time they seem to secure that the normalization will take place as fast as it has been demonstrated in an earlier study employing only 3 days of nasal packing. No synechias or perforations were seen at an early follow-up, 1-3 months postoperatively. When long-term packing is preferred, respiratory tubes then can be recommended as effective. PMID- 1448678 TI - Diagnostic value of plain radiographs in chronic maxillary sinusitis: a comparison between radiological and endoscopic findings in 75 patients. AB - Preoperative radiologic and intraoperative endoscopic findings of maxillary and ethmoid sinuses were compared in 75 adult patients, in whom 135 chronically inflamed maxillary sinuses were operated using functional endoscopic sinus surgery (FESS). At sinoscopy, secretion was found in 91% (41/45) of the radiologically opacified antra and in 47% (31/65) of the antra with moderate or marked mucosal swelling in plain radiographs. Antral fluid level in radiographs was a relatively rare (23%) finding and showed secretion as reliably as opacification. Radiographic detection of secretion in maxillary sinuses with mucosal thickening is difficult. There was a fair correlation in both antral and ethmoidal mucosal changes with the mucosal findings in antroscopy and endoscopic ethmoid surgery. PMID- 1448679 TI - [Acute intermittent porphyria in pregnancy: glucose or hematin therapy?]. AB - The symptoms and management of acute intermittent porphyria (AIP) during pregnancy and delivery are presented on the basis of three case reports. Two patients became asymptomatic after infusion of a concentrated glucose solution (600 ml 50% glucose = 300 g glucose per day), while the third patient needed treatment with hematin (1 mg/kg body weight, 6 infusions at intervals of 12 hours) because of deterioration of psychic state in spite of glucose infusion. Whenever an attack of AIP occurs, concentrated glucose solution should be administrated as a first measure accompanied by an analgesic and possibly a neuroleptic agent after elimination of precipitating factors. However, if symptoms persist for 48-96 hours or the psychic and/or neurological state of the patient further deteriorates, administration of 1-3 mg hematin per kg body weight can be recommended. PMID- 1448680 TI - [Long-term follow-up after thyroidectomy: incidence of recurrent goiter and functional results]. AB - We analyzed the postoperative longterm results after strumectomy for sporadic goiter in 26 patients. The follow-up time was 25.1 +/- 14.7 (7-58) years (x +/- SD, extremes). Actual goiter recurrence without need for surgery was observed and sonographically confirmed in 3 patients, and 1 patient without actual recurrence had had a second strumectomy for goiter recurrence in the past. Hence the overall frequency of goiter recurrence in this study is 15% (4/26 patients). The patients with a present recurrence (n = 3) were significantly younger at the time of operation (29 +/- 11, 14-41 years) than those without recurrence (n = 23; 45 +/- 11, 28-60 years; p < 0.001). No patient had clinical endocrine dysfunction. Only four patients had been treated with thyroxine and they all suppressed TSH in the presence of euthyroid FT4 and T3 levels without present recurrence of goiter. 22 patients had no thyroid hormone prophylaxis and in only four of them (18%) was observed a recurrence in the longterm follow-up without endemic iodine deficiency. Prophylaxis with thyroid hormones often is not required in low risk patients operated upon and carefully controlled after strumectomy from non-iodine deficient regions. Patients at risk for recurrence (second strumectomy, family history, elevated TSH, clinical or sonographic evidence for thyroid growth) should be considered for thyroxine therapy with regular follow-up. PMID- 1448681 TI - [Health status of methadone recipients before entering a methadone program]. AB - Data were analyzed from 905 opiate addicts who participated for the first time in a methadone maintenance program in the Canton of Bern, Switzerland, between 1979 and 1989. Data of their physical and psychological state at the time of application for the methadone maintenance program were related to data of the addiction history and program progress. Only one fifth of the participants in the methadone maintenance program report to be in good health. Poorer health corresponds to reported psychological disorders. No correlation between demographical data and health status could be found, except that less qualified patients were in poorer health. Poorer health status is associated with the consumption of a higher amount of heroin per kg body weight and often with consumption of benzodiazepines before entrance into the methadone maintenance program. Methadone maintenance patients with a lower health status are given higher methadone doses. Compared to patients in better shape, more do not work before and during the methadone program. The physicians express less optimism with regard to the success of the program in patients in poorer health, and these are more often expelled from the program by their physicians or the health department. The results indicate that patients generally profit from the methadone maintenance treatment. However, better integrated patients and persons in better health may derive greater benefit from the methadone maintenance treatment. PMID- 1448682 TI - [Do we still have Gothamite tricks today?]. PMID- 1448683 TI - [Concerning: "Incidence of ileus following rectal resection in rectal carcinoma with or without radiotherapy" by M. Els, T. Gross, Ch. Ackermann and P. Tondelli (Schweiz. med. Wschr. 1992; 122: 745-747)]. PMID- 1448684 TI - [Immunology and diagnostic test results in Lyme borreliosis]. AB - Borrelia burgdorferi (B. burgdorferi), the etiologic agent of Lyme borreliosis, shows both a variety of outer surface proteins with molecular weights between 16 and 100 kiloDalton (kD) and a 41 kD flagellar protein, which induce the immunologic response. Lipopolysaccharides, another constituent of the bacterial capsule, are responsible for the inflammatory reaction, constitutional symptoms and for the Jarisch-Herxheimer reaction. First a vigorous T-cell immune response develops, followed later by a more slowly evolving humoral B-cell immune response. The delayed onset of the humoral immune response may explain why antibodies against B. burgdorferi could not be detected early in the course of the disease. But the antibody titers increase with duration of the illness. The humoral response shows the usual pattern of IgM appearing first, followed by IgG and IgA. The IgM titer normalizes after recovery while the IgG titer could persist over years or decades. It is hardly possible to detect B. burgdorferi microscopically or by cultivation from blood, joint or cerebrospinal fluid. For routine diagnosis the fluorescent antibody staining and the ELISA methods are available which detect IgM or IgG antibodies against B. burgdorferi. But the sensitivity and specificity of these tests are still unsatisfactory. Other methods such as the ELISA-capture method, complement binding reaction, passive hemagglutination or the polymerase chain reaction are not yet established for routine purposes. Western blot analysis did not yield an essential diagnostic advantage but may be helpful in long term observation or in special cases. The measurement of the cellular immune response by T-cell proliferation tests remains controversial. First of all Lyme borreliosis has to be diagnosed by clinical findings and by elimination through differential diagnosis. An elevated antibody titer or a positive T-cell proliferation test may confirm the diagnosis but cannot prove it. Without consistent clinical findings they are of no practical significance. Some general guidelines for interpretation of laboratory results are given. PMID- 1448685 TI - [Abdominal aortic aneurysm. Risks and early postoperative course]. AB - A review of the literature shows a very variable mortality, especially after emergency operations for abdominal aortic aneurysm (AAA) (14-70%). We therefore analyzed the mortality of our patients in different subgroups. The hospital data of 82 patients operated on for abdominal aortic aneurysm were analyzed retrospectively. 42 patients underwent emergency operations and 40 patients elective surgery. The mean age was 67.5 +/- 9.4 and 70.7 +/- 7.3 years respectively. The overall 30-day mortality in elective cases was 5% (2/40); elective patients under the age of 75 years had a mortality of 0%. 33% of the emergency cases died within 30 days. The mortality in various subgroups was as follows: "asymptomatic AAA" 5.4% (2/37), "symptomatic AAA" 10% (1/10), "retroperitoneal rupture" 34% (11/32) and "intraperitoneal rupture" 66.6% (2/3). Preoperatively 21/42 patients who underwent emergency surgery were in hypovolemic shock (systolic blood pressure < or = 90 mm Hg). The mortality of these patients was 52% (11/21) compared to 9.5% (2/21), (p < 0.01), in emergency patients without preoperative shock. The causes of death after emergency procedures were hypovolemic shock in 6, heart failure in 4, and multi-organ failure, respiratory insufficiency, unknown and pulmonary embolism in 1 each. 5/14 patients died in theatre. Two patients died after elective procedures: one 9 days postoperatively from myocardial infarction and the second 23 days after the operation from an unknown cause. Reoperation rate after elective and emergency procedures was 7.5% and 16.6% respectively. Mortality after reoperation was 40%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448686 TI - [Fever of unknown origin in a cohort of HIV-positive patients]. AB - The purpose of this study was to determine the prevalence of fever of unknown origin (FUO) in a cohort of HIV positive patients and to describe their evolution and the final diagnosis. The clinical records of 412 patients followed from January 1987 to December 1990 at our HIV outpatient clinic were reviewed: in 151 patients 255 episodes of fever had been observed of which 22 (in 21 patients) met the criteria for FUO. 19 patients (90%) presented with a CDC/WHO stage IV HIV infection and the mean CD4+ lymphocyte count was 0.160 G/l. The etiology was ultimately determined in 13/22 episodes (3 Pneumocystis carinii pneumonia, 3 invasive infections due to atypical mycobacteria, 2 bacterial pneumonia, 1 Cytomegalovirus colitis, 1 Isospora belli enteritis, 1 visceral leishmania, 1 candida septicemia and 1 lymphoma). In 6/22 episodes, the fever subsided after zidovudine was started and was therefore attributed to HIV itself. In 3/22 episodes no etiology was found. In conclusion, this series shows that FUO is usually seen in advanced HIV infection and that it often represents an early sign of opportunistic infection. This observation underlines the importance of follow up, since it finally served to detect the etiology of FUO in 86% of cases. Trial treatment with zidovudine can be useful where no pathology has been discovered despite 3 weeks' follow-up and appropriate investigations. PMID- 1448687 TI - [Glomerulonephritis with transient C3 hypoclompimentemia and endotheliomesangial glomerulonephritis in childhood. A long-term experience]. AB - 62 children (20 girls and 42 boys, ranging in age between 3 and 15 years), presenting with acute hypocomplementemic glomerulonephritis or morphologically confirmed endotheliomesangial glomerulonephritis, were admitted to the University Children's Hospital, Berne from 1970 to 1991. The annual incidence of cases of acute hypocomplementemic glomerulonephritis was stable during the study period. The site of the antecedent infection was the throat in 26 patients, upper respiratory tract in 15, the skin in 9, and unknown in 10. The latent period ranged from 0.5 to 3.5 weeks. 41 patients developed hypertension and 17 renal failure. Hypertensive complications were observed in 6 patients and remitted completely in 5 cases. A nephrotic syndrome (edema, proteinuria of 40 mg/[m2.h], albuminemia < 25 g/l) was observed in 11 patients. Microscopic hematuria persisted in many patients for one year or more. Proteinuria remitted in all but one patient, who was found to have Alport syndrome. This study shows the stable frequency of hypocomplementemic glomerulonephritis since 1970, its good prognosis, and the importance of the measurement of C3-complementemia in children presenting with acute glomerulonephritis. PMID- 1448688 TI - [Acute poisoning due to oral intake of an organic solvent]. AB - We report a case of paint thinner intoxication by oral intake, with loss of consciousness, upper gastrointestinal injuries, renal failure, rhabdomyolysis and cervical plexus injury. The clinical picture was similar to other cases reported in the literature. PMID- 1448689 TI - [Awarding of the 7th Dr.-Josef-Steiner-Krebsforschungspreisen 1992 to Prof. Bernard Fisher and Prof. Gianni Bonadonna]. PMID- 1448690 TI - INR and ISI--a step forward! PMID- 1448691 TI - Management of the do-not-resuscitate patient undergoing anesthesia and surgery. AB - Some unique questions and concerns arise when a patient with do-not-resuscitate orders is taken to surgery. This issue is discussed in the context of current data on cardiopulmonary resuscitation and ethical decision-making strategies. PMID- 1448692 TI - Medical malpractice support group. PMID- 1448693 TI - The South Dakota Drug Education and Evaluation Program (DEEP) PMID- 1448694 TI - Enteral nutrition: past, present and future. PMID- 1448695 TI - Date and acquaintance rape among a sample of college students. AB - This article reports on a date and acquaintance rape needs-assessment survey of 106 male and 113 female students in undergraduate English courses at the University of Hawaii-Manoa. The sample was ethnically mixed, with Japanese being the largest ethnic group represented. Unduplicated counts showed that 28 percent (n = 32) of the women acknowledged that they were victims of rape or attempted rape, and the majority reported multiple victimizations. One-sixth (n = 18) of the men admitted to committing acts that meet the legal definition of sexual assault in Hawaii, and about one-third (29.2 percent, n = 31) admitted that they continue to make sexual advances even after a woman says no. Implications for date and acquaintance rape prevention programs are discussed. PMID- 1448696 TI - Elderly black farm women: a population at risk. AB - Elderly black farm women are a neglected segment of the elderly population. Their self-reliance, mutual support, and rurality have helped keep them isolated and underserved. This article describes the productive life-styles that 10 such women in southeastern North Carolina recalled in oral-history interviews and the problems these women face because of their advancing age, poor health, caregiving responsibilities, and isolation and the deterioration of traditional resources. PMID- 1448697 TI - Psychosocial implications of women and retirement. AB - This article explores the unique effects of retirement on women, many of whom are economically insecure when they retire. Because of the prevailing "myth" among women that they will be cared for in old age and women's fear of growing old, women often do not aggressively plan for their retirement. The women's movement should begin to advocate for women's preparation for the realities of old age. PMID- 1448698 TI - Kennel workers' grief needs addressing. PMID- 1448699 TI - [Indications for the use of metallic implants in the treatment of bone injuries]. PMID- 1448700 TI - [Results of a multicenter study in arthrography using a nonionic, dimeric x-ray contrast medium]. PMID- 1448701 TI - [Initial results in the quantification of fracture healing using computed tomography]. PMID- 1448702 TI - [Fatty tissue necrosis following breast-conserving breast cancer therapy. A diagnostic challenge]. PMID- 1448703 TI - [An unknown syndrome. 5 cases of a hereditary, until now not described symptomatology]. PMID- 1448704 TI - Towards an essential national health research strategy for South Africa. PMID- 1448705 TI - Primary health care--some lessons for South Africa. PMID- 1448706 TI - Guidelines for the development of health policy. I. Tertiary care and academic complexes (a discussion document). PMID- 1448707 TI - Understanding academic medicine. PMID- 1448708 TI - The setting of health research priorities in a new South Africa. PMID- 1448709 TI - Nosocomial colonisation and infection in a paediatric respiratory intensive care unit. AB - A study of the prevalence of nosocomial colonisation and nosocomial infection (NI) was conducted in the paediatric respiratory intensive care unit of a large teaching hospital serving a developing community. Surveillance specimens were collected regularly from 63 consecutive patients admitted over 4 months, and also from professional staff, boarder mothers, cleaners and the unit environment. The incidence among patients of colonisation (40%) and of NI (43%) was high. The risk of dying in children with NI was appreciably increased (relative risk 2,241, confidence interval 0,591-8,503). This did not reach statistical significance, probably because so few children escaped acquiring hospital organisms. The significant risk factor for acquiring colonisation (P = 0.008) and NI (P < 0.0001) was a ward stay of more than 10 days. In addition, for acquiring NI an age of under 6 months was also predictive (P = 0.0298). The nature of the primary illness dictated the time spent in the ward; an important proportion of patients had preventable diseases, such as measles, pneumonia and tetanus, which required prolonged treatment. All children with endotracheal intubation had hospital acquired organisms in tracheal aspirates. Eighty-two per cent of children developed positive gastric aspirates, 17% a positive urine culture and 11% a positive blood culture. Colonisation occurred rapidly; organisms initially appeared in gastric aspirates (mean 2 days), then in tracheal aspirates (mean 5 days) and urine cultures (mean 10 days). The acquired organisms, many of which were antibiotic-resistant, were almost exclusively enteric Gram-negative bacilli (GNB) and Staphylococcus aureus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448710 TI - Antibiotic susceptibility of anaerobic bacteria isolated in Johannesburg. AB - In vitro susceptibilities of 198 anaerobic bacteria to seven antibiotics were evaluated by the agar dilution method. In addition to testing amoxycillin/clavulanic acid in a 2:1 ratio against the bacteria, the combination was also tested against 63 isolates using fixed concentrations of clavulanic acid and serial dilutions of amoxycillin. Penicillin and cefoxitin were not effective against beta-lactamase-producing Bacteroides isolates and only 50% of isolates were susceptible to the 2:1 amoxycillin/clavulanic acid combination. However, when varying concentrations of amoxycillin were used together with constant concentrations of clavulanic acid (4 micrograms/ml) only 9 of 55 amoxycillin resistant Bacteroides were resistant to the combination. Two clostridia were found to produce beta-lactamases and as expected were resistant to penicillin. Of the non-beta-lactamase-producing clostridia 11% were resistant to penicillin and 5% resistant to cefoxitin. Imipenem was effective against the majority of anaerobes tested and only 5 Bacteroides isolates were resistant. All anaerobic strains were susceptible to chloramphenicol and only 6% of strains resistant to clindamycin. Eighty-five per cent and 51% of Bacteroides strains had minimum inhibitory concentrations within two dilutions of the breakpoints of chloramphenicol (16 micrograms/ml) and clindamycin (4 micrograms/ml) respectively. Three strains of Peptostreptococcus spp. were resistant to metronidazole. PMID- 1448711 TI - Safety and efficacy of interferon alpha-2b following prednisone withdrawal in the treatment of chronic viral hepatitis B. A case-controlled, randomised study. AB - The therapeutic effects of interferon alpha-2b (Intron A; Scherag) in patients with chronic active hepatitis caused by hepatitis B virus (HBV) were assessed in a randomised, case-controlled clinical trial conducted between January 1988 and June 1990. Treatment involved a short course of prednisone followed by interferon alpha-2b, initially 10 million U by subcutaneous injection, 3 times a week for 16 weeks. All patients were symptomatic, were known to have had hepatitis B surface antigen and hepatitis B e antigen (HBeAg) in their blood for at least 6 months, and had elevated serum aminotransferase activities with histological evidence of chronic active hepatitis. Patients with carcinoma, renal or haematological abnormalities or decompensated cirrhosis were excluded. In 6 of 10 patients randomised to receive interferon and 1 of 10 controls, HBeAg and HBV DNA were cleared from the blood during the 12-month study period (P < 0.05). An indeterminate response with clearance of HBV DNA but persistence of HBeAg was noted in 1 patient receiving interferon. Serum aminotransferase levels decreased only in those patients who had responded to treatment, but this did not reach statistical significance for the group as a whole. Histological studies, where available, showed decreased hepatic periportal necrosis in patients who underwent treatment. Two patients relapsed to HBeAg-positive status 2 months after their initial seroconversion; 1 became clear again during a repeat course of interferon. Side-effects of treatment were common and included fever, malaise, myalgias and myelosuppression. One patient developed hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448712 TI - A survey of the use of blood and blood components among South African anaesthetists working in teaching hospitals. AB - A survey of the peri-operative policies for blood and blood component therapy was carried out among anaesthetists in the nine South African teaching hospitals. All anaesthetists completed the questionnaire, without recourse to books or discussion. The survey revealed a possible over-utilisation of blood and blood components in the peri-operative period. There were significant deficiencies in the pre-operative assessment of blood and platelet requirements and the specific indications for platelet, fresh frozen plasma and blood transfusions. A significant number of respondents exhibited poor knowledge of the potential dangers and expense that the use of blood and blood components entails. Educational effort was perceived to be the main method of rationalising the anaesthetist's usage of blood and blood components. PMID- 1448713 TI - The role of private hospitals in South Africa. Part I. Current trends. AB - This paper is the first of two that examine the present and the future role of private hospitals in South Africa. Part I describes the current structure and size of the private hospital sector, and analyses recent trends in the number and distribution of beds and hospitals, expenditure patterns, and utilisation of care. These observations are used as the basis for an analysis of the present role of the private hospital sector. It is argued that this sector is an important potential national resource for health care. However, the present contribution of private hospitals to national health care is limited by several factors. Access to a large proportion of these hospitals is restricted to those who can afford to pay, while the economic inefficiency and geographical maldistribution of fee-for-service and charity hospitals compound the negative effect private hospitals have on the public health sector. The gap between the potential contribution of private hospitals and current reality provides a strong argument for the development of a national policy that will improve the situation. PMID- 1448714 TI - Psychiatric manifestations of neurosyphilis. AB - To investigate referral patterns, initial diagnoses and clinical features of patients with neurosyphilis who present with psychiatric manifestations, records were kept of 21 such patients admitted to an acute psychiatric ward. In none of the 12 cases referred from primary care workers was the possibility of neurosyphilis considered. In only 3 cases was this diagnosis considered on admission to the psychiatric ward before serum serological test results were known. Commonest presenting symptoms were personality change (16 patients) and memory impairment (13 patients). Neurological signs or symptoms were also common, particularly absent pupillary reaction to light (5 patients) and buccolingual masticatory movements (5 patients). A positive serological test remains the single most important factor in identifying patients with neurosyphilis. PMID- 1448715 TI - Indications for computed tomographic brain scanning in psychiatric inpatients. AB - This study examined the rate of use of computed tomographic (CT) scanning as well as clinical parameters pertaining to that used in psychiatric patients. These patients were compared with a randomly selected control group of psychiatric patients who were not scanned. In addition, scan abnormalities were examined and correlated with clinical and electro-encephalographic (EEG) data. CT scanning was used on 13.5% of admissions. On axis 1 of the DSM III-R, the CT scan group had a significantly higher incidence of delirium and dementia (P < 0.05) and a much higher rate of medical illness (P < 0.01) on axis 3. The rate of CT abnormality was fairly high at 45.2%. An abnormal CT scan was associated with the diagnosis of dementia, the presence of organic mental status abnormality and of abnormality on neurological examination. Focally abnormal CT scans were associated with focally abnormal EEGs in a significant number of patients (P < 0.05). PMID- 1448716 TI - The clinicoradiological profile of cerebral venous thrombosis. AB - The clinical presentation, diagnostic and radiological aspects and the probable aetiology in 20 consecutively studied patients with cerebral venous thrombosis (CVT) are described. In this retrospective analysis patients were evaluated extensively according to a stroke investigative protocol. Computed tomography signs for CVT may be identified in the majority of cases and frequently obviate the need for angiography. In those patients in whom no satisfactory precipitating factor was recognised further haematological tests revealed abnormalities that are known causes of thrombosis in 7 patients. Eighty-five per cent of the patients made an excellent recovery. It is concluded that CVT can often be diagnosed non-invasively, the presumptive cause can be found in the majority of patients and the prognosis is excellent. PMID- 1448717 TI - Elective cholecystectomy via a 5 cm subcostal incision. AB - This report describes a technique whereby elective cholecystectomy is performed through a 5 cm abdominal incision. Initial results in 18 patients compared with 112 historical control patients undergoing conventional cholecystectomy suggest an encouraging reduction in postoperative hospitalisation time, analgesic requirements and period of recuperation. The procedure takes no longer to perform than conventional cholecystectomy and obesity is not a limiting factor, as originally thought. This technique deserves a place alongside laparoscopic and conventional cholecystectomy in future studies seeking the optimal method of managing symptomatic cholelithiasis. PMID- 1448718 TI - The natural history of carcinoma of the cervix in young women. AB - Invasive carcinoma of the cervix was treated in 1,522 patients over a 10-year period at Groote Schuur Hospital. Data for each patient included place of residence, pathological characteristics of the tumour, nodal spread, histological evidence of human papillomavirus (HPV) infection, disease stage, treatment type, treatment complications, site of recurrence and survival time. Patients aged under 35 years comprised 11.6% of the total patient group. A retrospective cohort study compared women aged under 35 years of age at the time of entry into the study and women aged 35 years or more. In all, 82 eligible young patients were compared with random sample of 82 eligible older patients. Contingency tables, life tables and proportional hazards analysis were used where appropriate. There was no significant difference across the two age groups in the incidence of non squamous tumours, or in the grades of squamous tumours. Similarly there was no evidence of differences in lymph node involvement or HPV infection. Young patients appeared to enter the study at significantly earlier stages of the disease, and a greater proportion of them underwent surgical treatment (diff = 36.4% +/- 13.5%). In both groups treatment complications were less frequently observed after surgery than after radiotherapy. Sites of tumour recurrence were similar in both groups, and there was no apparent difference in survival times. PMID- 1448719 TI - [Failed postpartum sterilisation--a comparison of 5 methods]. AB - A comparison of the standard Vienna method of postpartum sterilisation (3,580 patients with 18 failures and a sterilisation failure rate of 5.03/1,000) with 4 other methods at Paarl Hospital is presented: the Pomeroy method (892 patients with 19 failures and a sterilisation failure rate of 21.31/1,000); the total fimbriectomy method (1,578 patients with 23 failures and a sterilisation failure rate of 14.58/1,000); the Filshie clip method (808 patients with 18 failures and a sterilisation failure rate of 22.28/1,000); and the Irving method performed at caesarean section (456 patients and 1 failure). As no totally permanent technique exists to prevent pregnancy, a plea is lodged for legalised abortion after failed sterilisation. PMID- 1448720 TI - Teenagers seeking condoms at family planning services. Part I. A user's perspective. AB - The promotion of condom use is an essential part of any AIDS prevention programme. By distributing condoms and promoting their use, clinics that provide family planning services can play an important role in preventing the spread of AIDS. This study assesses the accessibility of condoms to teenagers at selected family planning services in Durban. Twelve randomly selected clinics in Durban were visited by each of 4 teenage fieldworkers. During these visits, the fieldworkers' experiences were recorded in detailed notes which were subsequently analysed for content. The fieldworkers experienced difficulty in locating a few of the clinics and some were embarrassed by security staff. The two female fieldworkers, in particular, were intimidated by their reception at the clinics and found resistance to their requests for condoms. On two occasions, supplies of condoms had run out. When condoms were available, they were distributed in a setting that lacked privacy. Information on how to use condoms, if offered at all, was supplied by way of pamphlets and information on AIDS was rarely offered. Overall, the experiences of the fieldworkers indicated that it was difficult for teenagers to obtain condoms from clinics providing family planning services in Durban. It is recommended that there be signs indicating the location of the clinics, and that privacy be ensured and adequate stocks of condoms maintained. Most importantly, clinic staff need to use every opportunity to discuss AIDS prevention with teenagers attending the clinic. PMID- 1448721 TI - Teenagers seeking condoms at family planning services. Part II. A provider's perspective. AB - This study assessed the ability and preparedness of staff at family planning clinics in Durban to assist in AIDS prevention by promoting condom use among teenagers. Staff at 12 randomly selected clinics were interviewed to assess their attitudes towards teenagers seeking condoms, the information imparted on AIDS and condom use, constraints faced in delivering services, and their perceived role in controlling the spread of AIDS. Despite their awareness of AIDS, those interviewed perceived their role to be that of promoting contraception. Condoms were perceived as a poor choice of contraceptive and their use was discouraged. The pamphlets dispensed along with condoms were thought to provide adequate information about condom use. Information on AIDS was given only if the clinic attender initiated discussion on the subject. Most of the clinic staff were keen to discuss other issues during their consultations, but felt constrained by the large numbers of people they had to attend to and the lack of adequate facilities. If family planning services are to play a role in controlling the spread of AIDS, the first step must be to make this function part of the overall policy. For there to be effective counselling on AIDS prevention, in-service training of current staff is required, as well as more staff and improvements in facilities to ensure greater privacy. PMID- 1448722 TI - Perinatal statistics for the Cape Province. PMID- 1448723 TI - Should NSAIDs be used in rheumatoid arthritis? PMID- 1448724 TI - First the infant, then the schoolboy sans teeth. PMID- 1448725 TI - Tetracyclines in myalgic encephalomyelitis. PMID- 1448726 TI - Differentiation of miliary tuberculosis from miliary metastasis of the lung. PMID- 1448727 TI - HIV positivity and abnormal cervical cytology. PMID- 1448728 TI - Acinic cell carcinoma of the sublingual gland. PMID- 1448729 TI - Retroperitoneal in-line aortic bypass for treatment of infected infrarenal aortic grafts. AB - Since 1970, we have treated 43 patients with infected aortic grafts. Early in the series, four patients were treated with resection of the fistula or erosion and systemic and topical antibiotics without removal of the graft. All four patients died. Thirty-two patients were treated by conventional therapy; there were 13 deaths (40 percent). More recently, seven patients were managed by the left retroperitoneal placement of a new in-line polytetrafluoroethylene (PTFE) aortic graft through clean tissue planes, followed by the immediate transperitoneal removal of the infected graft without cross-contamination. Patients were maintained postoperatively on antibiotics for a minimum of two weeks. All seven patients survived without septic complications, with a mean follow-up time of 36 months (six months to four years). The surgical technique consists of initial suprarenal control of the aorta, followed by infrarenal division and oversewing of the distal aorta. A PTFE bifurcation graft is placed connecting the proximal aorta and the appropriate femoral vessels, the right limb tunneled through the space of Retzius. After closure of the incisions, through the space of Retzius. After closure of the incisions, the patient is placed in the supine position and the infected graft is removed transperitoneally. We believe that retroperitoneal in-line aortic bypass for treatment of an infected aortic graft offers a favorable alternative to conventional therapy by avoiding the use of an extra anatomic bypass and associated risk of stump blowout. PMID- 1448730 TI - Observations on prevention and management of vesicovaginal fistula after total hysterectomy. AB - A retrospective study of genital fistulas of the lower urinary tract revealed 91 percent to be postsurgical. Of these, 91 percent occurred after gynecologic procedures. Total hysterectomy was the most common antecedent procedure (n = 110), and the resulting lesion was the vault fistula. Abdominal total hysterectomy was the most frequent operation to precede a vault fistula (n = 92) and almost 70 percent occurred in the absence of factors identified as placing the patient at risk for injury to the bladder. Such risk factors included prior uterine operation, especially cesarean section, endometriosis, recent cold-knife cervical conization and prior radiation therapy. Twenty-four fistulas occurred despite recognition at the time of hysterectomy of injury to the bladder and its prompt repair. Thirty patients had undergone prior failed attempts at repair elsewhere. Three fistulas closed spontaneously. One hundred and seven were repaired by the Latzko technique. There were nine failures, each of which was successfully repaired by a repeat Latzko operation when vaginal reepithelization was complete. Suggestions to avoid injury to the bladder during abdominal total hysterectomy include use of a two-way indwelling catheter when risk factors are present, use of sharp dissection to isolate the bladder, use of extraperitoneal cystotomy when dissection is difficult, filling the bladder when injury is suspected and repair of an overt bladder injury only after mobilization of the injured area. A Latzko repair of a vault fistula is advised because complications are minimal, the postoperative patient is comfortable and the period of hospitalization is five days or less. PMID- 1448731 TI - The diagnosis and management of dystocia of the shoulder. AB - Dystocia of the shoulder is an unpredictable obstetric emergency that may result in injury to the mother or fetus. In an effort to reduce such risks, attempts have been made to identify patients having a fetus who may subsequently develop shoulder dystocia. The literature, however, clearly reflects that even the combination of prenatal historic facts, estimated fetal weight and sequence of intrapartum events is ineffective in prospectively identifying infants whose births are complicated by shoulder dystocia. During a ten year period at the University of Mississippi Medical Center, the incidence of macrosomia, shoulder dystocia and subsequent brachial plexus injury was reviewed. The majority of instances (89 percent) of shoulder dystocia occurred in patients weighing less than 8 pounds 13 ounces at birth. In the current retrospective review, only 11 percent of the women had risk factors for macrosomia or shoulder dystocia and among these, none were identified prospectively. Additionally, 91 percent of patients with brachial plexus injury recovered with no sequelae. One instance of brachial plexus injury occurred at the time of cesarean section. These data reveal that macrosomia and subsequent shoulder dystocia cannot be predicted. Therefore, it is not feasible to prevent brachial plexus injury prospectively by prophylactic cesarean section. Great clinical acumen and technical expertise by the obstetrician using a variety of methods may be useful in avoiding, as much as possible, injury to the mother and fetus when shoulder dystocia does occur. PMID- 1448732 TI - Surgical laparoscopic experience during the first year on a teaching service. AB - Recently, general surgeons have become actively involved in laparoscopic operations. The best method for teaching these techniques to surgical residents is unclear. Since June 1990, at St. Luke's-Roosevelt Hospital Center in New York City, we have instituted a formal course of instruction for surgical residents. This includes a reference syllabus, didactic instruction, use of an inanimate training device and a hands-on practice in swine. Clinically, the residents progress from observer to camera operator and, finally, operator. During the first year of this program, the authors performed 90 laparoscopic cholecystectomies, of which 71 were elective and 19 were for acute cholecystitis. There were seven morbidly obese patients, while 25 had undergone prior abdominal operations. The first 25 operations performed by the authors averaged 93.2 minutes, while the last 40 operations performed primarily by the surgical residents with assistance of the authors averaged 70 minutes. There were nine complications, including postoperative pancreatitis in two patients, Clostridium difficile enterocolitis in two and one each of prolonged paralytic ileus, postoperative transfusion and umbilical incision dehiscence. Two patients had postoperative common duct stones. There were no wound infections, bile duct injuries or deaths. Complications were evenly distributed throughout the series and did not correlate with whether the surgeon was a resident or an attending surgeon. The results of this plan have been quite successful and thus far, 12 residents have completed this program. PMID- 1448733 TI - Prospective comparison of partial versus total portal decompression for bleeding esophageal varices. AB - Eighty-six patients underwent portacaval shunt (PCS) to treat bleeding esophagogastric varices during a period of four years. Twenty-eight patients (group 1) underwent emergency total portal decompression, while 58 patients (group 2) underwent elective partial PCS. Age, gender, preshunt and postshunt alcohol consumption and modified Child-Pugh classification at the time of operation, and at latest follow-up evaluation, did not differ significantly between the two groups. Early mortality was higher after emergency shunts than after elective operation (p < 0.01). However, partial portal decompression, when compared with total shunt, resulted in a significantly lower likelihood of late mortality (13 versus 39 percent) (p < 0.05), as well as portasystemic encephalopathy (8 versus 56 percent) (p < 0.0005). All shunts remained patent postoperatively and no patient had variceal rebleeding during follow-up evaluation averaging 2.2 years. Duplex sonography demonstrated hepatofugal portal flow in all patients in both groups. The results of the current study suggest that partial portal decompression is technically feasible, prevents further variceal hemorrhage and confers significant protection against late mortality and the development of postshunt neuropsychologic dysfunction. PMID- 1448734 TI - Cardiovascular changes during laparoscopic cholecystectomy. AB - Although the technique of laparoscopic cholecystectomy has increasing appeal, physiologic data to support the safety of this procedure are lacking. We studied the cardiovascular changes in 16 patients undergoing laparoscopic cholecystectomy, using impedance cardiography as a noninvasive means of continuous monitoring of cardiac output. Serial measurements of mean arterial pressure (MAP), heart rate (HR), intraperitoneal pressure and expired carbon dioxide tension (PECO2) were also recorded. Results revealed a decrease of 30 percent (p < 0.001) in cardiac index and 5 percent (p = 0.089) in HR, along with increases of 15 percent (p < 0.001) in MAP and of 79 percent (p < 0.001) in the calculated total peripheral resistance index. This elevation in afterload could lead to both an increase in myocardial oxygen consumption and to the potential risk of myocardial ischemia and possibly infarction or congestive heart failure, or both, in patients who are susceptible. The data suggest that patients with a history of cardiac disease should have preoperative cardiac evaluation and be closely monitored during laparoscopic cholecystectomy, as in any other extensive operation. PMID- 1448735 TI - Reassessment of preoperative laboratory testing has changed the test-ordering patterns of physicians. AB - To test the hypothesis that physicians have substantially reduced the ordering of unwarranted preoperative tests, the authors reviewed 2,093 medical records of patients having four surgical procedures performed at three institutions in three cities in 1979, 1981, 1983, 1985 or 1987. Excluding hemoglobin measurements, the incidence of ordering preoperative laboratory tests unwarranted by findings on history or physical examination decreased from 32.2 to 25.9 percent during this decade, representing a 19.6 percent reduction. This decrease was irregular and varied from operation to operation, test to test and institution to institution. Overall, the percentage of preoperative tests ordered that were unwarranted decreased from 66.9 percent in 1979 to 60.1 percent in 1987. Extrapolating these results, the authors estimate that more than $320 million was saved annually by elimination of unwarranted tests and that the potential savings could exceed $1.35 billion a year. Unexpectedly, the preoperative ordering of medically indicated tests also decreased (from 92.9 to 80.9 percent, representing a 12.9 percent reduction). Because the benefit of performing justified tests is probably greater than the benefit of avoiding unwarranted tests, the net change has probably not been beneficial. A better system for obtaining justified tests and for eliminating the unwarranted tests may be necessary before a net benefit occurs. Punitive measures to reduce testing without prior establishment of such a system may save money, but impair health. PMID- 1448736 TI - Microbiologic factors of stump wound infection. AB - Specimens from 52 patients with stump wound infection (SWI) were studied for aerobic and anaerobic bacteria. Bacterial growth was present in 44 specimens. Only aerobic or facultative bacteria were recovered in 19 specimens, only aerobic bacteria in 12 and mixed aerobic, facultative and anaerobic bacteria in 13. One hundred and three isolates were recovered (2.3 per specimen)-58 aerobic or facultative (1.3 per specimen) and 45 anaerobic (1.0 per specimen). The predominant isolates were anaerobic cocci (17), Bacteroides species (13 isolates), Staphylococcus aureus (12) and Escherichia coli (11). Polymicrobial infection occurred in 36 instances. S. aureus was more commonly isolated and anaerobic bacteria were less commonly isolated in SWI of the arms, compared with legs. These data highlight the polymicrobial aerobic-anaerobic cause of SWI. PMID- 1448737 TI - The importance of the endopelvic fascia repair during vaginal hysterectomy. AB - During 1985 to 1989, 177 vaginal hysterectomies were performed in the Department of Gynecology, Kaplan Hospital, Rehovot, Israel, using the Porges technique with some modifications. Ninety patients had some degree of loss of the pelvic support -anterior or posterior wall relaxation, enterocele or uterine prolapse in various degrees. The patients were allocated to two groups, in which two different techniques were compared: group 1, with repair of the pubocervical and pararectal fascia and group 2 without the repair. The repair of the pubocervical and pararectal fascia after vaginal hysterectomy prevented vaginal vault prolapse (zero versus 15 percent, p < 0.01) and reduced the incidence of recurrent rectocele (23 versus 55 percent, p < 0.05) and recurrent cystocele (14 versus 45 percent, p < 0.005). Recurrent genuine stress incontinence was found in 9 percent of patients in group 1 and 18 percent of patients in group 2 (not statistically significant; p = 0.163). Optimal management of relaxation of the vaginal wall during vaginal hysterectomy requires clinical suspicion and precise preoperative diagnosis and therapeutic plan. In the present study, the need for careful repair of the pubocervical and pararectal fascia during vaginal hysterectomy to prevent vaginal vault prolapse is emphasized. This procedure does not prolong the operation significantly (92 +/- 15 versus 84 +/- 17 minutes) and has no deleterious postoperative complications. PMID- 1448738 TI - Immunoperoxidase confirmation of ultrasonically guided fine needle aspirates in patients with recurrent hyperparathyroidism. AB - Fine needle aspiration (FNA) biopsy in conjunction with ultrasonic definition of nonpalpable masses in the neck region is being used more frequently. Currently available preoperative localization tests have failed, in many instances, to delineate adequately the location of missed adenomas of the parathyroid gland. We describe herein the use of ultrasonically guided FNA of parathyroid tissue with immunoperoxidase confirmation for precise localization of the diseased gland. Three patients with persistent hypercalcemia after exploration of the neck were referred to Ochsner Clinic, New Orleans. In two of these patients, a parathyroid adenoma had been removed, while in one patient no adenoma was found. All patients had elevated calcium (range 10.9 to 11.6 milligrams per deciliter), low phosphorous and elevated parathyroid levels. Preoperative ultrasonography to localize the suspected parathyroid glands was performed, with FNA and immunohistochemical confirmation. Smears confirmed adequate cellular material. Alcohol fixed, Papanicolaou stained and air dried, Wright's and Giemsa stained smears were evaluated for the presence of parathyroid cells by conventional cytologic examination. The Papanicolaou-stained slides were then decolorized in 1 percent hydrochloric acid in 70 percent ethanol. After decolorization, the smears were stained for parathyroid hormone (PTH) in an avidin-biotin complex (ABC) system, using a commercially available ABC kit (Vector Laboratories Inc.). The primary antibody is a polyclonal antiserum generated in rabbits against a synthetic human PTH. Negative controls were obtained from normal thyroid glands. In all three patients, the diseased gland was localized by ultrasound with cytologic and immunohistochemical confirmation, one on the right side and two on the left side. At surgical excision, the adenomas weighed 0.8 and 0.75 gram and the carcinoma, 0.75 gram. In two, intraoperative identification of the diseased gland was aided by ultrasound directed methylene blue injection into the adenoma. During a follow-up evaluation of eight to 24 months, serum calcium had remained normal in two patients, and one patient had become hypocalcemic and required calcium supplements. The preoperative localization allowed a direct surgical approach to the side in question in all patients. Ultrasonically guided FNA in an immunoperoxidase system can be a valuable preoperative localization technique for patients with recurrent hyperparathyroidism, thus avoiding extensive exploration of the neck with the subsequent complications. PMID- 1448739 TI - Local antibiotic prophylaxis in inguinal hernia repair. AB - We compared the effects of single dose (750 milligrams) prophylactic cefamandole delivered directly into the operative wound with local anesthesia (n = 162) with a control group (no antibiotics) (n = 162) in a randomized trial. No adverse effects were observed. There were seven wound abscesses in the untreated group compared with none in the group receiving antibiotic prophylaxis (p = 0.007). Six of the seven abscesses occurred as late as one month after the patient was discharged from the hospital. The costs of antibiotics used were ten times less than the costs of treatment of wound complications in the control group. PMID- 1448740 TI - T-tube management of late esophageal perforations. PMID- 1448741 TI - A simple modification of choledochoenterostomy using continuous pull through suture. AB - A simple modification of choledochoenterostomy is described. Using continuous suture and pull through technique, the posterior line of the anastomosis is completed without immediate approximation of the two structures. By improving the access, good control of the posterior suture line is ensured, the risk of anastomotic leakage is minimized and the use of stent or T tube is unnecessary. PMID- 1448742 TI - A new technique for ureteral stent placement during pregnancy using endoluminal ultrasound. AB - Endoluminal sonography using the IVUS is a minimally invasive procedure performed using a flexible 6.2F catheter with a 20 megahertz transducer that can easily be passed endoscopically to image the urethra, bladder, ureter and renal pelvis. In the current study, a woman patient in her third trimester of pregnancy with a renal pelvic stone and persistent colic was safely treated with placement of an indwelling ureteral stent. Because it is minimally invasive and does not require the use of roentgenograms, we believe the IVUS will be a useful tool to assist with the management of ureteral colic in patients who are pregnant in whom intervention is required. PMID- 1448743 TI - New York State Health Department ruling--a "wake-up call" for all. PMID- 1448744 TI - Endosurgical revolution, or convergence of multiple technical and socioeconomic realities? PMID- 1448745 TI - Colonoscopic impaction in left colon strictures resulting in right colon pneumatic perforation. AB - Colonic perforation during flexible colonoscopy is a rare but recognized complication. We reviewed 4,593 colonoscopies performed from 1984 to 1989. The perforation rate for diagnostic colonoscopy was 0.17% (6/3,538) and for therapeutic colonoscopy it was 2% (21/1,055). Four perforations of the right colon occurred at a site proximal to the level of the impacted colonoscope. The lesions being evaluated were obstructive in nature: two diverticular strictures (sigmoid colon), one ischemic stricture (descending colon), and one annular carcinoma (descending colon). The four perforations occurred in the right colon and manifested as distension with pneumoperitoneum or retroperitoneal emphysema. Operative management included total abdominal colectomy in two patients (ileoproctostomy in one and ileostomy in one) and right colectomy in two. Outcome was favorable in all cases. PMID- 1448746 TI - Correlative histologic and arthroscopic evaluation in rheumatoid knee joints. AB - The correlation between arthroscopic observations and histologic changes in rheumatoid arthritis is still controversial. Synovial samples of 21 knee joints in rheumatoid arthritis patients were comparatively investigated by endoscopy and histology. Biopsies were scored by an endoscopist and subsequently dissected. Different histochemical and immunocytochemical staining techniques were used to define inflammatory activity. Arthroscopic and histological values were compared by rating scales and variance analysis. Our study indicates that synovial biopsy is of diagnostic value in rheumatoid arthritis. However, its usefulness depends on the histochemical methods used. The results revealed highly significant correlations of endoscopic features with the number of neutrophilic granulocytes, intravascular leukocytes, and peroxidase-positive macrophages. However, no relationship was found between the detection of lymphocytes or resident macrophages and inflammatory scores. The close correlation between endoscopic and histological findings suggests that arthroscopic evaluation allows a valuable classification of the inflammatory activity in rheumatoid synovitis. PMID- 1448747 TI - Mesenteric venous thrombosis. Modern management and endoscopic diagnosis. AB - Mesenteric venous thrombosis has an obscure etiology, a prolonged onset of symptoms, and controversial methods of diagnosis and treatment. Eleven collected patients with pathologic confirmation of this diagnosis are presented, with one patient demonstrating the endoscopic appearance of this disease in human small bowel. Other methods of diagnosis are also reviewed. Treatment of mesenteric venous thrombosis requires resection of necrotic bowel and, we believe, anticoagulation. The role of planned "second-look" laparotomy is reviewed, but it was not necessary in those patients in whom definitive resection could be combined with intraoperative anticoagulation. PMID- 1448748 TI - Laparoscopic tube cholecystostomy. AB - Tube cholecystostomy was offered to 100 patients undergoing laparoscopic cholecystectomy as an alternative to open surgery should the gallbladder be found too severely inflamed for safe removal. At the time of surgery, three of the 100 patients had gallbladders judged too severely inflamed for laparoscopic cholecystectomy. They therefore underwent laparoscopic placement of a cholecystostomy tube. The patients received 48 h of antibiotics in the hospital and then underwent tube drainage for 4-6 weeks as outpatients. They returned to the hospital for interval laparoscopic cholecystectomy. The three patients underwent successful interval laparoscopic cholecystectomy. There were no complications. Of the 100 patients in the study, conversion to open cholecystectomy was not necessary for any of the patients. Tube cholecystostomy is a safe and effective procedure. It should reduce the number of patients who require open surgery for removal of the gallbladder. PMID- 1448749 TI - Concomitant placement of percutaneous endoscopic gastrostomy and jejunostomy. AB - Percutaneous endoscopic gastrostomies have gained wide use for long-term enteral nutrition. However, gastroesophageal reflux and aspiration pneumonia have occurred following this procedure. Initial enthusiasm concerning the ability of intrajejunal feeding to negate the risk of aspiration has been challenged by some reports. In this report, a new method is described for concomitant placement of endoscopic gastrostomy and feeding jejunostomy wherein the tip of the feeding jejunostomy is placed at least 40 cm distal to the pylorus while the gastrostomy tube is used for drainage. Twenty critically ill patients underwent the procedure utilizing general or local anesthesia. Sixty-day follow-up showed one uneventful episode of pulmonary aspiration (5%) after retrograde migration of the jejunal tube into the duodenum. All but two patients (90%) tolerated their tube feedings well. This technique can be easily performed with accurate placement of the PEJ tube distal to the pylorus and is associated with minimal risk of aspiration. PMID- 1448750 TI - Is laparoscopic better than open appendectomy? AB - Laparoscopic appendectomy is becoming increasingly popular as surgeons strive to manage surgical problems via minimally invasive techniques. We reviewed our early experience in 38 patients with laparoscopic appendectomy and compared it to open appendectomies done during the same time period. We found no difference in hospital costs, stay, or wound infection rate. There was a significant difference in OR time: the laparoscopic approach took longer. We conclude that this new approach is not clearly superior to open appendectomy despite theoretical advantages. Newer instruments and further studies are needed. PMID- 1448751 TI - Diagnostic laparoscopy in critically ill intensive-care-unit patients. AB - The diagnosis of intraabdominal sepsis in critically ill intensive-care-unit patients remains a challenge. Diagnostic laparoscopy has been performed in seven such patients following admission for coronary artery bypass surgery, gram negative sepsis, major burns, pneumonia, myocardial infarction, and post pneumonectomy. Laparoscopy revealed acalculous cholecystitis in two patients (one removed laparoscopically), gangrenous colon in two, cirrhosis with liver infarction in one, and, in two patients, no pathology. Although five patients died postoperatively, none was related to the laparoscopy. There were no intraoperative complications and no known pathology was missed. Because of its ease and accuracy, diagnostic laparoscopy should be considered in all critically ill patients suspected of harboring intraabdominal pathology. Further studies are needed to fully establish its efficacy and safety. PMID- 1448752 TI - Laparoscopic splenectomy--technical aspects. AB - Since the recent development of endoscopic cholecystectomy various other digestive disorders have been treated endoscopically. Using the endo-GIA stapler the authors report a case of laparoscopic splenectomy. Five trocar sheaths were used. Once detached, the spleen was cut into fragments in a plastic bag intraabdominally, which allowed its removal. Splenectomy was performed for a girl who had an autoimmune thrombocytopenic purpura (ITP). No operative transfusion was required. The patient was discharged after an uncomplicated postoperative recovery. The cosmetic result is good. PMID- 1448753 TI - LaparoLith. A new instrument for stone fragmentation in laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy can be performed with incisions of a maximum diameter of 10 mm. The removal of a stone-filled gallbladder at the end of an operation via the 10-mm port needs often-extensive tissue-consuming manipulations for stone removal or minilaparotomy. Stone fragmentation can be achieved by mechanical crushing and by ultrasound-, electrohydraulic-, and tunable dye laser lithotripsy. The clinical employment of the LaparoLith (Baxter Healthcare Corporation), an instrument which allows mechanical fragmentation of stones inside the gallbladder, is presented here. We have used the LaparoLith in nine patients and have been successful in stone fragmentation in seven of these. The LaparoLith seems to be helpful in laparoscopic cholecystectomy, preventing extension of the subnavel incision. PMID- 1448755 TI - [Firing according to qualification. A nasty stamp. Interview by Mette Flordbo]. PMID- 1448754 TI - The pneumoperitoneum technique by ultrasonographic guide. PMID- 1448756 TI - [Firing according to qualifications. Like holding on to a time bomb]. PMID- 1448757 TI - [Smoking policy]. PMID- 1448758 TI - [Drug cardex--avoid medication errors]. PMID- 1448759 TI - [International Nurses Day. A healthy old age]. PMID- 1448760 TI - [Executive Board]. PMID- 1448761 TI - [Education--courses nearby]. PMID- 1448763 TI - [Health for all. Ecology and nursing]. PMID- 1448762 TI - [Education--advantages of scholarships]. PMID- 1448764 TI - [Nursing care in endoscopy]. PMID- 1448765 TI - [Clinical nursing--endoscopy]. PMID- 1448766 TI - [Firing according to qualifications. Those, who best can be done without...]. PMID- 1448767 TI - Lysosomal membrane glycoproteins in platelets. PMID- 1448768 TI - Des-gamma-carboxyprothrombin (PIVKA II) and plasma vitamin K1 in newborns and their mothers. AB - Assessments of the vitamin K status in newborns and their mothers by means of des gamma-carboxy-prothrombin (PIVKA II) measurement have given equivocal results. Part of the variability could be attributed to differences in sensitivity (i.e. the ability to detect small concentrations) and validity (i.e. ability to detect vitamin K deficiency) of the methods applied. None of these methods have yet been validated with respect to plasma vitamin K1. In 22 healthy mother/infant pairs PIVKA II was determined using three different assays including ratio Xa/ecarin (Xa/ec), crossed immunoelectrophoresis (CIE), and an ELISA with a monoclonal antibody (MAB). The results were compared with conventional clotting tests and plasma vitamin K1. The following results were obtained: Cord blood: Clotting tests within age-related normal ranges; PIVKA II detection rates: 0/22 (Xa/ec), 1/22 (CIE), 4/22 (MAB); plasma vitamin K1: undetectable in 20/22. Mothers: Clotting tests all within normal range; PIVKA II detection rates: 1/22 (Xa/ec), 0/22 (CIE), 5/22 (MAB); plasma vitamin K1 (pg/ml) for all mothers (median; range): 186; 55-833; for PIVKA II positive mothers: 213; 59-699. PIVKA II detectability in newborns and mothers was not correlated. The results show an increase in sensitivity for PIVKA II detection in the order of MAB >> CIE > Xa/ec. Due to the very low plasma vitamin K1 at birth, no correlation was possible between cord PIVKA II detectability and plasma vitamin K1. However, in mothers at term PIVKA II MAB appears to be unrelated to the vitamin K status. PMID- 1448769 TI - Reduction in factor VII, fibrinogen and plasminogen activator inhibitor-1 activity after surgical treatment of morbid obesity. AB - The aim of this study was to determine the effects of the surgical treatment of morbid obesity on some aspects of haemostatic and fibrinolytic function. Measurement of haemostatic and fibrinolytic factors was performed before and again 6 and 12 months after operation in 19 patients suffering from morbid obesity. Surgical treatment resulted in a mean decrease in body weight of 50 kg at 6 months and 64 kg at 12 months. Weight loss was accompanied at 12 months by significant reductions in median (interquartile range) concentrations of serum cholesterol from 5.3 (4.5-6.2) mmol/l to 3.6 (2.9-4.6) mmol/l; factor VII from 113 (92-145)% of normal to 99 (85-107)%; of fibrinogen from 3.5 (3-9.3) g/l to 2.8 (2.4-3.8) g/l; and of plasminogen activator inhibitor-1 (PAI-1) activity from 21 (11-30) IU/ml to 6.3 (5-10) IU/ml. The decrease in PAI-1 activity probably accounted for a significant reduction in euglobulin clot lysis time. Tissue plasminogen activator activity was undetectable in most patients pre-operatively but increased slightly after 1 year to 110 (100-204) mIU/ml. There were no significant changes in plasma levels of KCCT, factor VIII, von Willebrand factor antigen, alpha-2-antiplasmin, antithrombin III, protein C antigen, beta thromboglobulin, platelet factor 4, fibrinopeptide A or platelet count. These findings provide support for the hypothesis that the surgical treatment of morbid obesity may have a long-term beneficial effect on mortality from cardiovascular and thromboembolic disease. PMID- 1448770 TI - Enhancement of spontaneous fibrinolytic activity in diabetic retinopathy. AB - The fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes. PMID- 1448771 TI - The production of a factor X activator by a methylcholanthrene-induced rat fibrosarcoma. AB - The association between neoplasia and thrombosis has been well documented. We have studied the production of a procoagulant which is a factor X activator in a rat fibrosarcoma model. Extracts of excised tumor were assayed in a one stage clotting assay using normal and factor deficient human plasmas. The activity was not due to tissue factor, as acceleration of clotting was observed in FVII deficient plasma. No activity was noted in FX deficient plasma. The activator was capable of cleaving 125I-FX in the absence or presence of calcium. A radioimmunoassay (RIA) demonstrated a 5,100-fold increase in the levels of FX activation peptide after exposure to sarcoma extract. The FX activation occurs in the absence of calcium although the effect is greatly accelerated in the presence of 5 mM CaCl2. Using a two-stage amidolytic assay, functional activation of FX by the sarcoma was demonstrated. Inhibitor studies suggest that the sarcoma-derived procoagulant is a serine protease. The methylcholanthrene-induced rat sarcoma may serve as a useful model for investigating the regulation and effects of cancer procoagulants. PMID- 1448772 TI - Multicentric evaluation of a new assay for prothrombin fragment F1+2 determination. AB - A multicenter study of a recently developed ELISA for the determination of prothrombin fragment F1+2 was performed in order to evaluate analytical and clinical aspects. Mean intra-assay and inter-assay reproducibility were found to be 11.0 and 12.6%, respectively. The measuring range covered by the calibration curve reaches from 0.04 to 10.0 nM/l F1+2. Testing 133 healthy subjects a reference range of 0.37 to 1.11 nM/l F1+2 (2.5-97.5 percentile) with a median of 0.66 nM/l F1+2 was calculated. Minor difficulties with blood sampling (venous occlusion for 2 min) did not affect F1+2 plasma concentrations. Significantly increased F1+2 levels were measured in patients with leukemia (p < 0.0001), severe liver disease (p < 0.005) and after myocardial infarction (p < 0.01). Elevated F1+2 concentration before the beginning of heparin therapy (1.25 nM/l) decreased to 0.77 nM/l (p < 0.0001) after 1 day of therapy. For patients in the stable phase of oral anticoagulant therapy decreasing F1+2 concentrations were measured with increasing INR. F1+2 levels were already significantly reduced in patients with INR < 2.0 (0.56 nM/l; p = 0.0005). Thus F1+2 determination may be helpful in identifying activation processes as well as in monitoring anticoagulant therapy. PMID- 1448773 TI - Influence of the xanthine derivate HWA 138 on endotoxin-related coagulation disturbances: effects in non-sensitized vs D-galactosamine sensitized rats. AB - We have evaluated the effects of the xanthine derivate HWA 138 in rat endotoxemia in order to 1) prevent coagulation disturbances and other endotoxin-induced physiological abnormalities and 2) to reduce mortality. We performed two studies using two different models (sensitized vs non-sensitized rats) with a similar mortality but different severity of coagulation disturbances: a) LPS (15 mg/kg) alone or with HWA 138 (80 mg/kg) as a treatment modality 30 min pre LPS, b) galactosamine (500 mg/kg) simultaneously with LPS (100 micrograms/kg) with or without HWA 138 (80 mg/kg) pretreatment. Experiments c) and d) employed D galactosamine and/or LPS similar to experiments a) and b), while HWA 138 was applied simultaneously. We found significant 1) amelioration of life-threatening coagulation disturbances in non-sensitized rats, 2) prevention of liver dysfunction in sensitized rats, 3) reduction of TNF formation in both models, and 4) improvement of survival in all groups receiving HWA 138. Our data indicate protective effects of HWA 138 against clotting disturbances either directly via reduced LPS-induced formation of procoagulant activity or indirectly via reduced TNF formation. PMID- 1448774 TI - Prevention of thrombus growth by antithrombin III-dependent and two direct thrombin inhibitors in rabbits: implications for antithrombotic therapy. AB - We compared the abilities of heparin and two direct thrombin inhibitors to prevent fibrin accretion onto pre-existing thrombi in rabbits. Inhibition of thrombus growth was measured as the ability of each test compound to inhibit the accretion of 125I-fibrin onto thrombi pre-formed in jugular veins of rabbits. When administered as a continuous infusion, the two direct (i.e. antithrombin III independent) thrombin inhibitors, r-hirudin and a tripeptide, Ac(D)-Phe-Pro-bor Arg (P-8714) inhibited fibrin accretion as effectively as heparin, but did so in doses which generated little systemic anticoagulation, as compared to the marked anticoagulation associated with the heparin effect. However, both r-hirudin and P 8714 were more effective when they were administered as a single bolus injection than as a continuous infusion. Under the former conditions, there was only a transient systemic anticoagulant effect. We conclude that direct or antithrombin III-independent thrombin inhibitors are more effective than heparin in preventing thrombus growth. The limited effect of heparin is likely due to fibrin impairing the ability of heparin/antithrombin III to inactivate thrombin. PMID- 1448775 TI - Collaborative study of a proposed international standard for plasma fibrinogen measurement. AB - There is increased interest in the relationship between plasma fibrinogen levels and the incidence of coronary artery disease. The National Institute for Biological Standards and Control (UK) has completed a study to establish an International Standard for plasma fibrinogen. This study was conducted using a recommended assay procedure to measure the clottable material present in the proposed lyophilised Standard (coded 89/644). Twenty-two laboratories from nine countries took part in the study and analysis of the data allowed the calibration of 89/644 at 2.4 mg/ml clottable protein. Agreement with this figure was established in two laboratories using three or more different assays for plasma fibrinogen. Degradation studies of the proposed plasma fibrinogen Standard suggested that no loss of clottable protein was observed when the lyophilised material was stored at 20 degrees C for 1 year. The Fibrinogen Sub-Committee of the ISTH (Amsterdam, The Netherlands, June 1991) supported the establishment of 89/644 as an International Standard. This collaborative study will be presented to the Expert Committee on Biological Standardisation of the World Health Organisation at their 1992 session. In the meantime 89/644 will be distributed as the proposed International Standard for plasma fibrinogen measurement containing 2.4 mg/ml clottable protein. PMID- 1448776 TI - Pharmacokinetic properties of recombinant factor VIII compared with a monoclonally purified concentrate (Hemofil M). The Recombinate Study Group. AB - A recombinant FVIII preparation, Recombinate, was compared with a high-purity plasma-derived concentrate, Hemofil M, in 47 hemophilia A patients in a cross over evaluation of pharmacokinetic properties. The recombinant material showed a significantly lower clearance, volume of distribution, and higher in vivo recovery, but a similar half-life to the plasma-based product. In a comparison with reported data from other standard concentrates, the recombinant preparation exhibited potentially better pharmacokinetic properties in that its clearance was slower and its half-life was longer. We conclude that the recombinant DNA method of preparation does not adversely affect the biological and pharmacological characteristics of the factor VIII molecule. PMID- 1448777 TI - The hemodynamic and fibrinolytic response to low dose epinephrine and phenylephrine infusions during total hip replacement under epidural anesthesia. AB - Lower rates of deep vein thrombosis have been noted following total hip replacement under epidural anesthesia in patients receiving exogenous epinephrine throughout surgery. To determine whether this is due to enhanced fibrinolysis or to circulatory effects of epinephrine, 30 patients scheduled for primary total hip replacement under epidural anesthesia were randomly assigned to receive intravenous infusions of either low dose epinephrine or phenylephrine intraoperatively. All patients received lumbar epidural anesthesia with induced hypotension and were monitored with radial artery and pulmonary artery catheters. Patients receiving low dose epinephrine infusion had maintenance of heart rate and cardiac index whereas both heart rate and cardiac index declined significantly throughout surgery in patients receiving phenylephrine (p = 0.0001 and p = 0.0001, respectively). Tissue plasminogen activator (t-PA) activity increased significantly during surgery (p < 0.005) and declined below baseline postoperatively (p < 0.005) in both groups. Low dose epinephrine was not associated with any additional augmentation of fibrinolytic activity perioperatively. There were no significant differences in changes in D-Dimer, t PA antigen, alpha 2-plasmin inhibitor-plasmin complexes or thrombin-antithrombin III complexes perioperatively between groups receiving low dose epinephrine or phenylephrine. The reduction in deep vein thrombosis rate with low dose epinephrine is more likely mediated by a circulatory mechanism than by augmentation of fibrinolysis. PMID- 1448778 TI - The anatomical distribution of plasma fibrinolytic activity in man during cardiac catheterisation. AB - Regional circulating plasma levels of fibrinolytic activity were assessed in 15 patients undergoing cardiac catheterisation. The euglobulin clot lysis time (ECLT) was longer in the abdominal aorta (AA) than the inferior vena cava (IVC), (median difference -17.5 min, p = 0.008). This was associated with higher inhibition of plasminogen activator activity (PAI) in the AA than IVC, -1.75 IU/ml, p = 0.002. In the venous circulation the ECLT was higher in the peripheral venous sample than in the IVC, -25.5 min, p = 0.003, with higher PAI peripherally than in the IVC, -1.9 IU/ml, p = 0.001. There were no differences in ECLT, PAI, PAI-1:Ag or t-PA:Ag throughout the arterial circulation. These results demonstrate higher fibrinolytic activity with lower inhibitor activity in the venous compared to the arterial circulation. Within the venous circulation fibrinolytic activity is lower peripherally with increased inhibitor activity. PMID- 1448779 TI - Mutations in severe, type III von Willebrand's disease in the Dutch population: candidate missense and nonsense mutations associated with reduced levels of von Willebrand factor messenger RNA. AB - The von Willebrand factor (vWF) genes of nine unrelated, severe, type III von Willebrand's disease (vWD) patients (six of Dutch origin) and four unrelated Dutch type I vWD patients were screened for mutations in exons that contain CGA codons (Arg), which are liable to mutation to TGA stop codons. The nine exons of the vWF gene (3, 8, 9, 10, 28, 31, 32, 43 and 45) that contain all the CGA codons (11 in total) of the vWF cDNA were amplified by the polymerase chain reaction and screened for mutations by single-strand conformation polymorphism analysis, restriction enzyme - and/or nucleotide sequence analysis. Three of the severe vWD patients were found to be heterozygous for a nonsense mutation: CGA Arg 2535- >TGA Stop. Three other severe vWD patients were homozygous for a single nucleotide substitution, AAC Asn 2546-->TAC Tyr. The transcription of these mutated alleles was tested by cDNA dependent amplification of platelet RNA. The level of transcription product was strongly reduced for either mutant allele. PMID- 1448780 TI - Comparison of the inhibitory effects of the TXA2 receptor antagonist, vapiprost, and other antiplatelet drugs on arterial thrombosis in rats: possible role of TXA2. AB - The antithrombotic effect of the thromboxane A2 receptor antagonist, vapiprost, was compared with those of other antiplatelet drugs using an arterial thrombosis model which utilized photochemical reaction in the rat femoral artery. Vapiprost prolonged the time required to occlude the artery with thrombus and inhibited collagen-induced rat platelet aggregation in whole blood ex vivo, in a dose dependent manner. The potency ranking of antithrombotic effect was vapiprost > ketanserin (serotonin 5-HT2 receptor antagonist) >> ticlopidine (inhibitor of ADP induced platelet aggregation) = dipyridamole (adenosine uptake inhibitor) > aspirin (cyclooxygenase inhibitor). On the other hand, the ranking of antiplatelet effect was ticlopidine > or = vapiprost > or = aspirin. Ketanserin and dipyridamole were ineffective. Relative to their antiplatelet effect, vapiprost and ketanserin had powerful antithrombotic effects. It is possible that the potent antithrombotic effects of vapiprost and ketanserin in vivo reflect the ability of these drugs to inhibit mediator-induced vascular contractions in addition to platelet aggregation. The results of the present study also suggest that TXA2 may play an important role in thrombogenesis in rats. PMID- 1448782 TI - A high titre "spontaneous" porcine FVIII inhibitor. PMID- 1448781 TI - Hereditary protein C-deficiency: laboratory values in transmitters and guidelines for the diagnostic procedure. Report on a study of the SSC Subcommittee on Protein C and Protein S. Protein C Transmitter Study Group. AB - A multicenter study on protein C-antigen and -activity values was carried out in transmitter patients with hereditary protein C deficiency (diagnosis established by pedigree analysis) and in normal controls in order to (1) establish the range of protein C levels in genetically determined heterozygotes and (2) to evaluate the usefulness of statistical procedures to discriminate between protein C deficient patients and controls. In transmitters absolute protein C activity values ranged from 19 to 82% and antigen values from 22 to 88.5%. Most transmitter patients could clearly be differentiated from the control group. However, in some transmitter patients values of protein C were within the range of the control group. The discrimination between transmitters and controls could be improved by statistical procedures. Using tolerance ellipses the overlapping area of the two groups was smallest when (factor II antigen+factor X antigen)/2 was plotted against protein C antigen. To specify the degree of uncertainty likelihood ratios were calculated to obtain the posterior probability for an individual for being deficient or not. In quadratic discriminant analysis the best discrimination between transmitters and controls was obtained using protein C activity versus factor X antigen and protein C antigen versus factor X antigen. Based on these analysis an equation was derived, which allows the calculation of the likelihood ratio favouring deficiency or non-deficiency in an individual. PMID- 1448783 TI - Erythropoietin doping in athletes: possible detection through measurement of fibrinolytic products. PMID- 1448784 TI - PPACK-thrombin is a noncompetitive inhibitor of alpha-thrombin binding to human platelets. AB - Recent studies from our laboratory indicate that purified kininogens are noncompetitive inhibitors of human alpha-thrombin but not PPACK-thrombin, binding to human washed platelets. In order to understand the mechanism by which the kininogens inhibit alpha-thrombin binding, investigations were initiated to determine if alpha-thrombin and PPACK-thrombin bound to the same site on human platelets. Initial investigations reveal that alpha-thrombin is a more potent inhibitor of 125I-PPACK-thrombin binding than PPACK-thrombin. Further studies show that PPACK-thrombin is a noncompetitive inhibitor of 125I-alpha-thrombin binding to platelets. These studies suggest that human alpha-thrombin binds on the platelet surface to a different site or binds differently to the same site from PPACK-thrombin. These data indicate that the ability of the kininogens to block alpha-thrombin binding to platelets but not PPACK-thrombin binding results from these thrombins having either two different binding sites or one binding site on the platelet surface which they interact with differently. PMID- 1448785 TI - Kinetics of merthiolate-induced aggregation of human platelets. AB - Incubation of human platelet-rich plasma (PRP) or washed platelets with merthiolate (MT; sodium ethylmercurithiosalicylate; an inhibitor of lysophosphatide: arachidonoyl transferase) leads to irreversible platelet aggregation which is parallelled by an increase in thromboxane A2 synthesis. MT induced aggregation is preceded by a pronounced lag-period (0.5-10 min). Duration of the latter is inversely related to the concentration of MT ([MT]). Platelet responses to MT are similar to those triggered by arachidonate (AA) in that the relationships of the aggregation rates both to [MT] and [AA] are threshold and exhibit characteristic super-high values of the apparent Hill coefficients (h > 30). A typical MT-induced response can be subdivided in two sequential phases: i) cyclooxygenase-independent slow aggregation, and ii) indomethacin-abrogated rapid aggregation. MT-induced responses are blocked by PGE1 or ajoene (which inhibits binding of fibrinogen to its cell surface receptor, GPIIb/IIIa). The obtained data are interpreted both quantitatively and qualitatively in terms of a model assuming the existence of: i) a relationship between the rate of MT-inhibitable AA incorporation into phospholipids and the concentration of intracellular free AA, [AA]i; ii) a certain threshold value of [AA]i essential for triggering the second phase of the aggregation. PMID- 1448786 TI - Binding of annexin V to a human ovarian carcinoma cell line (OC-2008). Contrasting effects on cell surface factor VIIa/tissue factor activity and prothrombinase activity. AB - Proteins of the annexin/lipocortin family bind tightly to anionic phospholipids and platelets and act as in vitro anticoagulants. Annexins may be useful as tools to study the availability of anionic phospholipids on cell surfaces and their role in the regulation of blood coagulation. In the present study, we investigated the binding of annexin V (placental anticoagulant protein I) to a human ovarian carcinoma cell line, OC-2008, that constitutively expresses surface membrane tissue factor activity. Binding of annexin V to cell monolayers was calcium-dependent, specific, saturable and reversible; Scatchard analysis indicated a single class of binding sites with an apparent Kd of 9.4 +/- 3.1 nM and 5.2 +/- 1 x 10(6) sites per cell. Binding was completely inhibited by phospholipid vesicles containing phosphatidylserine, but was not inhibited by vesicles containing phosphatidylcholine. Annexin V inhibited the cell surface dependent activity of prothrombinase complex, but did not inhibit the activity of the factor VIIa/tissue factor complex. In conclusion, these results suggest that anionic phospholipid is present on the extracellular face of OC-2008 cells; this anionic phospholipid is functionally important for the activity of the prothrombinase complex, but the importance of anionic phospholipid for the cell surface factor VIIa/tissue factor functional activity is unclear. PMID- 1448787 TI - The inhibitory effect of 9-amino-1,2,3,4-tetrahydroacridine (THA) on platelet function. AB - Tetrahydroacridine (THA), or Cognex, is currently awaiting FDA approval for the treatment of Alzheimer's disease. In addition to reports indicating that THA improves the symptoms of patients with Alzheimer's disease, we have found that THA possesses potent antiplatelet activity. THA produced dose-dependent inhibition of human platelet aggregation induced by collagen, ADP, A23187, and phorbol ester. THA, when added to activated platelets, dispersed the platelet aggregates. We have also examined the effects of THA on intracellular Ca++ mobilization, ATP release, and production of cyclic AMP. PMID- 1448788 TI - 1-Deamino-8 D-arginine vasopressin decreases the production of 13 hydroxyoctadecadienoic acid by endothelial cells. AB - 1-Deamino-8 D-arginine vasopressin (DDAVP) has been used effectively to normalize the bleeding time in various hemostatic disorders. In von Willebrand disease the reduction in bleeding time is due to the preferential release of large multimers of von Willebrand factor from endothelial cells. However, since the bleeding time correction in patients with uremia and liver disease is independent of the release of von Willebrand antigen and activity, other mechanisms of action of DDAVP need to be considered. Endothelial cells generate several thromborepellant factors including 13-hydroxyoctadecadienoic acid (13-HODE), an inhibitor of platelet adhesion to subendothelium. Using cultured fetal bovine aortic endothelial cells (FBAECs), we have investigated whether DDAVP modulates the production of 13-HODE. We have demonstrated that 14C-linoleic acid labeled FBAECs release several oxygenated derivatives of linoleic acid following a 120 min incubation in the presence of serum. One of these products was identified by chromatographic procedures as 13-HODE. The production of 13-HODE was decreased significantly by DDAVP (1-100 ng/ml) with maximal reduction (approx. 25%) seen at 1 ng/ml of DDAVP. While vehicle treated control FBAECs generated 6780 +/- 690 cpm of 13-HODE per 10(6) cells (mean +/- SE, n = 8), DDAVP treated FBAECs produced 4950 +/- 310 (P < 0.01), 5390 +/- 390 (P < 0.01), and 5720 +/- 410 cpm (P < 0.05) of 13-HODE at 1, 10, and 100 ng/ml DDAVP respectively. Our findings of a decrease in 13-HODE would explain the previously observed morphologic changes of increased platelet adhesion to subendothelium following DDAVP infusion and contributes to our understanding of the mode of action of this therapeutic agent in hemostatic disorders. PMID- 1448789 TI - The acute effect of a single very high dose of N-3 fatty acids on coagulation and fibrinolysis. AB - The objective of the study was to investigate the acute effect of a single very high dose of n-3 PUFA on coagulation and fibrinolysis. Forty healthy volunteers were randomized into two groups to receive either 20 grams of n-3 PUFA or 20 grams of n-6 PUFA as a single dose at 6 p.m. with their evening meal. Coagulation and fibrinolysis were evaluated in the fasting state at 8 a.m. the next morning and compared to values obtained at 8 a.m. the day before, when the participants were on their habitual diets. PAI-1 activity in plasma increased by a mean of 62% in subjects randomized to receive n-3 PUFA despite that no changes could be demonstrated in t-PA antigen levels. PAI-1 activity was unaltered in the 20 controls receiving n-6 PUFA. Plasma fibrinogen, coagulation factor VII, thrombin antithrombin complexes and D-dimer did not significantly change after either supplement. The substantial increase in levels of PAI-1 activity in plasma after a single very high dose of n-3 PUFA may limit the usefulness of single very high doses of n-3 PUFA in acute clinical conditions. PMID- 1448790 TI - The vascular plasminogen activator as source of the fibrinolytic potential observed during cardiopulmonary bypass. AB - Increased fibrinolytic activity is a well recognized constant finding observed during cardiopulmonary bypass (CPB). The purpose of the present work was to study and estimate the factors involved in the plasminogen activation and prekallikrein kallikrein systems in a population of adult patients undergoing open heart surgery with CPB. Plasminogen activator activity determinations with a fibrinolytic method as well as plasminogen activation and prekallikrein kallikrein determinations with synthetic substrates were carried out. Our results indicate that no active fibrinolysis but a fibrinolytic potential, similar to that observed in blood obtained after venous occlusion, can be demonstrated in circulating plasma during CPB. This fibrinolytic potential is related to the presence of vascular plasminogen activator released from endothelial cells by the CPB stimulus. PMID- 1448791 TI - Anticardiolipin antibodies in heparin-associated thrombocytopenia. PMID- 1448792 TI - Markers of coagulation activation in inherited protein S deficiency. PMID- 1448793 TI - Calcium binding to abnormal fibrinogens with a single amino acid replacement in the NH2-terminal region of fibrin alpha- or beta-chain. PMID- 1448794 TI - Effect of endothelin on the release of tissue plasminogen activator and plasminogen activator inhibitor-1 from cultured human endothelial cells and interaction with thrombin. PMID- 1448795 TI - Altered primary haemostasis in Conn's syndrome. PMID- 1448796 TI - Molecular mechanism of hemolymph clotting system in Limulus. AB - Limulus (horseshoe crab) hemolymph is known to be very sensitive to bacterial endotoxin (LPS), which causes a rapid coagulation response. Hemolymph contains a single type of hemocyte that undergoes aggregation, adhesion, and degranulation in response to LPS. The granule contents are released into the hemolymph, where they form an insoluble gel. We have characterized four components involved in this coagulation response that comprise a cascade of three serine protease zymogens (factor C, factor B, and proclotting enzyme) and one clottable protein (coagulogen). Of these components, factor C sensitive to LPS is a protein composed of five complement-related domains ("Sushi" or SCR), an EGF-like domain, and a C-type lectinlike domain as well as a putative amino-terminal LPS-binding domain. This domain structure is very similar to that of selectin family of cell adhesion molecules, suggesting that it might also function as a cell adhesion molecule after the release into the hemolymph. Factor B and the proclotting enzyme share a common Cys-rich motif ("cliplike" domain) in the amino-terminal portions. This domain is also found in a putative serine protease zymogen ("easter") in Drosophila, which is essential for normal embryonic development. All four of the components of the cascade and an antibacterial protein (anti-LPS factor) are localized to a specific type of the hemocyte granule. Another antibacterial peptide (tachyplesins I and II) is localized in a distinct granule population. The contents of both granule populations are released into the hemolymph in response to LPS, where they cooperate in immobilization and killing of Gram-negative bacteria. PMID- 1448797 TI - Increased procoagulant activity in peripheral blood mononuclear cells from patients with liver cirrhosis. PMID- 1448798 TI - Low dose infusion of adenosine diphosphate prolongs bleeding time in rats and rabbits. AB - The effect of intravenous infusion of adenosine diphosphate (ADP) on haemostatic and thrombotic mechanisms was studied in rats and rabbits. Infusion of ADP (0.2-1 microMol/kg/min) in rabbits prolonged the skin capillary bleeding time threefold after between 1/2 and 2 hours of infusion. Prolongation of the bleeding time was parallelled by reduced in vitro sensitivity of platelets to ADP in citrated platelet-rich plasma. No major changes in respiratory frequency and heart rate were observed. On the other hand, infusion of adenosine (1 microMol/kg/min) did not affect the bleeding times. Intravenous ADP (0.1 microMol/kg/min) significantly prolonged the bleeding time in anaesthetized rats. Platelet and red cell counts before and during the ADP infusion indicated slight, reversible platelet aggregation. After 75 min the ratio between red cells and platelets resumed a steady pre-experimental level. Platinum wires placed in the abdominal aorta of rats to monitor thrombus formation during ADP infusion indicated an antithrombotic effect of prolonged, low dose infusion of ADP. Since infusion of adenosine did not affect the haemostatic mechanisms, these observations may indicate that ADP infusion desensitized the platelet responsiveness to aggregating stimuli in vivo, and/or that prostacyclin production by endothelium was stimulated by infusion of ADP. PMID- 1448799 TI - Different effects of A23187 and PMA on palmitoylated platelet proteins. AB - The effect of agonists on palmitoylated proteins was examined in platelets prelabeled with [3H]palmitic acid. Non-reduced gels revealed major labeled proteins with masses from 30-38 kDa. One of these proteins was modified by A23187, which led to a loss of radioactivity, and PMA, which altered its electrophoretic mobility. A possible link between the A23187-induced loss of label associated with the protein and the activation of calpain was suggested by the following experiments. (1) There was a good correlation between the loss of label and the proteolysis of proteins in A23187-activated platelets. (2) The permeant calpain inhibitor, E64d, blocked the loss of label as well as the proteolysis of proteins. (3) The loss of label also occurred in a Triton lysate, where calpain was known to be activated. The effect of PMA on the palmitoylated protein was observed only in prelabeled platelets. The protein kinase inhibitor, staurosporine, abolished the PMA-induced platelet aggregation as well as the mobility shift of the labeled protein. PMID- 1448801 TI - Factor VIII/von Willebrand factor levels in plasma frozen to-30 degrees C in air or halogenated hydrocarbons. PMID- 1448800 TI - Thrombin-induced shape change in human megakaryoblastic leukemic cells, MEG-01, is mediated by protein kinase C. AB - We investigated the intracellular processes of the shape change in human megakaryoblastic leukemic cells, MEG-01, by platelet agonists. Thrombin induced the formation of many pseudopods. This shape change was also induced by phorbol 12-myristate 13 acetate (TPA) and weakly by Ca2+ ionophore, A23187, but not by ADP, collagen, or epinephrine. Electron microscopy and FITC-labeled phalloidin staining revealed thick submembranous microfilament bundles in the pseudopods of the shape-changed cells by thrombin. Shape change was inhibited by cytochalasin B. Since Ca(2+)-dependent phosphorylation reactions play central role on the initiation of shape change of platelet, we examined the effects of protein kinase C (PKC) inhibitor, H-7, and myosin light chain (MLC) kinase inhibitor, ML-9, on the shape change of MEG-01 cells induced by thrombin, and observed that H-7 potently inhibited thrombin-induced shape change, while ML-9 did not. These results suggest that thrombin-induced reorganization of microfilaments and shape change of MEG-01 cells are mediated by PKC, but not by MLC kinase. PMID- 1448802 TI - [Theme: growth hormone. Introduction]. PMID- 1448803 TI - [Historical perspective on growth hormone treatment in children]. AB - The history of growth hormone treatment can be divided into two episodes. Between 1958 and 1985 growth hormone was extracted from human pituitaries. Because of the scarcity little scientific research was carried out and efficacy was not optimal. In 1985 biosynthetic growth hormone became available, which facilitated research on the use of growth hormone for various indications. In the future further research is needed on the pathophysiology of growth disturbances, on methods to improve efficacy, and on possible side-effects of pharmacological dosages. PMID- 1448804 TI - [Good things come in small packages? Psychosocial aspects of small stature]. AB - Short stature is considered as a social disadvantage. This review deals with the findings of studies on cognitive and socio-emotional functioning in children with growth hormone deficiency, constitutional short stature, Turner syndrome, skeletal dysplasias and chronic illnesses. The consequences of short stature in adulthood are also described. The short term effect of growth hormone treatment on psychosocial functioning appears positive, but long term results have to be awaited before conclusions can be drawn. PMID- 1448805 TI - [Turner syndrome: a virtually certain indication for growth hormone treatment]. AB - Short stature is a feature in almost all cases with Turner syndrome. The etiology is unknown, but GH secretion appears to be normal. The treatment with anabolic steroids does not seem to increase final height. Oestrogens are needed for secondary sex characteristics, but should be given in a low dosage and at approximately 12-13 years of age, in order not to compromise final height. Growth hormone increases growth velocity and leads to an average gain of 5 cm in terms of final height. The addition of oxandrolone leads to an even higher growth rate, but final height is probably similar to that reached by growth hormone alone. The dosage, injection frequency, age and bone age at the start of therapy have influence on the efficacy. GH in the dosages given appears safe. PMID- 1448806 TI - [Growth hormone treatment in short stature of unknown origin]. AB - Most children with idiopathic short stature can be classified under the diagnoses familial short stature and constitutional delay of growth and adolescence. Administration of growth hormone leads to faster growth, but also faster bone maturation. Daily injections are more efficacious than three injections per week. There is a dose-response relationship. In a Dutch prospective study, the acceleration of growth was only slightly more than bone age advance, so that the average predicted adult height increased only by 3 cm over a period of 4-5 year. In an untreated control group final height was 1 cm lower than predicted. There were great inter-individual differences in terms of growth and bone maturation, which could not be predicted on the basis of clinical and biochemical variables. PMID- 1448807 TI - [Intra-uterine growth retardation: an indication for treatment with growth hormone?]. AB - Children with intra-uterine growth retardation (IUGR) constitute a heterogeneous group. Classification and etiology of IUGR are given. This report presents data on postnatal growth, growth hormone (GH) secretion and GH-therapy in children with short stature after IUGR, which was not based on a chromosomal disorder or a syndrome, with exception of Silver-Russell Syndrome (SRS). During the first two years of life, 86% of the children with IUGR showed spontaneous catch-up growth to a height above the third percentile, while only 14% did not. Sixty to eighty percent of the children with poor catch-up growth showed an insufficient GH secretion, despite of the fact that most children did not show the typical, clinical characteristics of children with classical growth hormone deficiency. GH therapy leads to increased growth velocity, but so far only short-term results have been reported. No serious adverse events were observed. The individual growth responses were heterogeneous, but no difference was shown in the response between the sexes or between those with or without SRS. It is still unclear whether GH-therapy will improve final height and which factors enable detection of patients who will most likely benefit from GH-therapy. Only long-term clinical trials until final height will answer those questions. PMID- 1448808 TI - [Chronic kidney insufficiency: results of treatment with growth hormone]. AB - Stunted growth is a serious problem for many children with chronic renal insufficiency (CRI). Dialysis does not improve growth velocity, while renal transplantation does not always result in better growth either. The pathogenesis of the growth retardation is unknown, but growth hormone (GH) secretion and plasma levels of insulin-like growth factors (IGF) I and -II appear to be normal. Elevated levels of IGF-binding proteins may be involved in the growth retardation. Several 2-year studies have shown that impressive increase in growth velocity can be achieved with GH therapy with 28 IU/m2/week, without significant changes in renal function or adverse events. A lower GH dose of 14IU/m2/week was not able to maintain catch-up growth for longer than 6 months in children older than 4 years. Bone maturation appears unaffected, suggesting improved final height. In children with CRI GH-treatment is best started following 1 year of marked growth retardation. Preliminary results of GH-treatment in children after renal transplantation seem promising, but long-term data are needed before definitive conclusions can be drawn. PMID- 1448809 TI - [Growth hormone therapy in dysmorphic syndromes and chronic disease]. AB - Many clinical syndromes are associated with short stature, which can be proportionate or disproportionate. In the first group of syndromes, such as Turner syndrome and its variants, Down syndrome, Prader-Willi-Labhart syndrome, Noonan syndrome, and Silver-Russell syndrome growth hormone therapy can lead to increased growth velocity, but so far only short-term results have been reported. Growth hormone is contraindicated in syndromes with an increased risk of chromosomal breakage, e.g. Bloom syndrome. In disproportionate syndromes, such as hypochondroplasia, pseudopseudohypoparathyroidism, spina bifida, and hypophosphataemic rickets, the results of growth hormone therapy are not encouraging. Growth hormone therapy in children with rheumatoid arthritis and thalassaemia appears little effective. Long-term clinical trials of reasonable size are needed before reliable conclusions can be drawn about the value of growth hormone therapy in these conditions. PMID- 1448810 TI - Synthetic approaches toward total synthesis of 12 beta-methyl- and 12-methylene 19-norpregnanes. AB - The effect of a substituent in the 12-position of progestagens was studied. To this end, various approaches toward the preparation of 12 beta-alkyl- and 12 alkylidenenorpregnanes were investigated. Eventually, the desired compounds 17 beta-hydroxy-12 beta-methyl-18a-homo-19-nor-17 alpha-pregn-4-en-20-yn-3-one (37) and 17 beta-hydroxy-12-methylene-18a-homo-19-nor-17 alpha-pregn-4-en-20-yn- 3-one (38) were obtained in racemic form by total synthesis; they were shown to lack progestagenic activity. PMID- 1448811 TI - Synthesis of N-acetylglucosaminides of unconjugated and conjugated bile acids. AB - 3-N-Acetylglucosaminides of unconjugated, glycine- and taurine-conjugated bile acids have been synthesized. Bile acids appropriately protected were condensed with acetochloroglucosamine through the 3 alpha-hydroxyl group by means of the Koenigs-Knorr reaction using cadmium carbonate as a catalyst. Subsequent borohydride reduction and/or alkaline hydrolysis provided desired 3-N acetylglucosaminides of unconjugated bile acids. Glycine-conjugates were obtained from N-acetylglucosaminides of unconjugated bile acids and ethyl glycinate by the carbodiimide method. The preparation of N-acetylglucosaminides of taurine conjugates was attained by the Koenigs-Knorr reaction of bile acid p-nitrophenyl esters followed by condensation with taurine. 7-N-Acetylglucosaminides of ursodeoxycholates were prepared in a similar fashion. The convenient synthesis of 3-N-acetylglucosaminides of unconjugated bile acids is also described. PMID- 1448812 TI - Synthesis of deuterium-labeled 5 alpha-androstane-3 alpha, 17 beta-diol and its 17 beta-glucuronide. AB - Using unlabeled androsterone as starting material, 5 alpha-[16,16-2H2]androstan-3 alpha-ol-17-one was synthesized by exchange using deuterated potassium methoxide. This labeled androsterone product was reduced by sodium borodeuteride, which gave predominantly trideuterated 5 alpha-androstane-3 alpha, 17 beta-diol. The labeled androstanediol was conjugated with glucuronide by using the Koenig-Knorr reaction with methyl-1-bromo-1-deoxy-2,3,4-tri-O-acetyl-alpha-D-glucopyranosuronate . The dominant product was identified by thermospray high-performance liquid chromatography/mass spectrometry (MS) and electrospray MS as 5 alpha-[16,16,17 2H3]androstane-3 alpha, 17 beta-diol, 17 beta-glucuronide. PMID- 1448813 TI - 17-Epimerization of 17 alpha-methyl anabolic steroids in humans: metabolism and synthesis of 17 alpha-hydroxy-17 beta-methyl steroids. AB - The 17-epimers of the anabolic steroids bolasterone (I), 4 chlorodehydromethyltestosterone (II), fluoxymesterone (III), furazabol (IV), metandienone (V), mestanolone (VI), methyltestosterone (VII), methandriol (VIII), oxandrolone (IX), oxymesterone (X), oxymetholone (XI), stanozolol (XII), and the human metabolites 7 alpha,17 alpha-dimethyl-5 beta-androstane-3 alpha,17 beta diol (XIII) (metabolite of I), 6 beta-hydroxymetandienone (XIV) (metabolite of V), 17 alpha-methyl-5 beta-androst-1-ene-3 alpha,17 beta-diol (XV) (metabolite of V), 3'-hydroxystanozolol (XVI) (metabolite of XII), as well as the reference substances 17 beta-hydroxy-17 alpha-methyl-5 beta-androstan-3-one (XVII), 17 beta hydroxy-17 alpha-methyl-5 beta-androst-1-en-3-one (XVIII) (also a metabolite of V), the four isomers 17 alpha-methyl-5 alpha-androstane-3 alpha,17 beta-diol (XIX) (also a metabolite of VI, VII, and XI), 17 alpha-methyl-5 alpha-androstane 3 beta,17 beta-diol (XX), 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol (XXI) (also a metabolite of V, VII, and VIII), 17 alpha-methyl-5 beta-androstane 3 beta,17 beta-diol (XXII), and 17 beta-hydroxy-7 alpha,17 alpha-dimethyl-5 beta androstan-3-one (XXIII) were synthesized via a 17 beta-sulfate that spontaneously hydrolyzed in water to several dehydration products, and to the 17 alpha-hydroxy 17 beta-methyl epimer. The 17 beta-sulfate was prepared by reaction of the 17 beta-hydroxy-17 alpha-methyl steroid with sulfur trioxide pyridine complex. The 17 beta-methyl epimers are eluted in gas chromatography as trimethylsilyl derivatives from a capillary SE-54 or OV-1 column 70-170 methylen units before the corresponding 17 alpha-methyl epimer. The electron impact mass spectra of the underivatized and trimethylsilylated epimers are in most cases identical and only for I, II, and V was a differentiation between the 17-epimers possible. 1H nuclear magnetic resonance (NMR) spectra show for the 17 beta-methyl epimer a chemical shift for the C-18 protons (singlet) of about 0.175 ppm (in deuterochloroform) to a lower field. 13C NMR spectra display differences for the 17-epimeric steroids in shielding effects for carbons 12-18 and 20. Excretion studies with I-XII with identification and quantification of 17-epimeric metabolites indicate that the extent of 17-epimerization depends on the A-ring structure and shows a great variation for the different 17 alpha-methyl anabolic steroids. PMID- 1448814 TI - Studies of the synthesis of biomarkers. XI. Synthesis of 4,5-secocholestane and 4 methyl-4,5-secocholestane. AB - 4,5-Secocholestane (1a) and 4-methyl-4,5-secocholestane (1b) were synthesized from cholesterol (2) in five and seven steps, respectively. The key intermediate, 5-oxo-4,5-secocholestan-4-al (7) was reduced by the Clemmensen method to afford 1a. Meanwhile, 7 underwent selective Wittig reaction, Clemmensen reduction, and hydrogenation to give another target molecule, 1b. The structure of an unknown biomarker was shown to be different from the proposed 1a by gas chromatographic and mass spectrometric comparison. PMID- 1448815 TI - Application of time-series analysis for the recognition of increases in urinary estrogens as markers for the beginning of the potentially fertile period. AB - Time-series analysis was applied to the urinary total estrogen data from 142 ovulatory menstrual cycles to determine the first statistically significant increase as a marker for the beginning of the potentially fertile phase. Application of the Trigg's tracking signal to each cycle detected an increase in urinary total estrogens above the baseline in every case, with a cumulative probability of > or = 95%. The distribution of first increase days ranged from 10 days before 3.5 days before the presumed day of ovulation with a mean of 6.5 +/- 1.4 days. The significant parameters in the calculation of the tracking signal are the smoothing constant (alpha) which is related to the number of baseline observations, the baseline mean for the cycle, and the variation of the baseline mean. The method allows a calculation of the tracking signal as the cycle unfolds and a statistical assessment can be given each day. The procedure is easily adaptable for computer calculation, and because it is applied to individual cycles avoids the use of population means with the loss of information inherently associated with the combination of data from many cycles. The Trigg's tracking signal is an appropriate method of analysis of menstrual cycle data and represents a satisfactory alternative to the more usual cumulative sum procedure. The distribution of the first increases constitutes a reference standard for urinary estrogen assays. PMID- 1448816 TI - H-1, C-13, and F-19 nuclear magnetic resonance assignments of 3,3-difluoro-5 alpha-androstane-17 beta-ol acetate. AB - The molecular structure of 3,3-difluoro-5 alpha-androstane-17 beta-ol acetate was analyzed by 1H, 13C, and 19F nuclear magnetic resonance (NMR) techniques; two dimensional NMR was used to assigned 1H and 13C resonances. The 1H NMR spectrum in deuterated chloroform shows three sharp singlets (delta = 0.74, 0.79, and 2.00 ppm) integrating for three protons each, an isolated triplet at 4.55 ppm integrating for one proton, and overlapping multiplets between 0.72 and 2.12 ppm integrating for 31 protons. The 13C spectrum shows 18 resonances between 10 and 55 ppm, and three additional resonances at 82.9, 124.0, and 171.5 ppm. The 19F[1H] spectrum shows two sets of doublets (observed 2J = 150 Hz) at 5.00 and 4.80 ppm. Multiplets arising from 19F-13C J-coupling provide the starting assignment for all resonances by means of 1H homonuclear correlation (COSY) and 1H-13C heteronuclear correlation spectroscopy. PMID- 1448817 TI - Marked increase of stroke incidence in men between 1972 and 1990 in Frederiksberg, Denmark. AB - BACKGROUND AND PURPOSE: Stroke incidence declined until the end of the 1970s in the United States, and the decline continued into the 1980s in Japan. The purpose of this study was to determine possible temporal changes of stroke incidence in a European community. METHODS: A prospective stroke registry was established in the community of Frederiksberg (population, approximately 90,000), Denmark, in the two periods 1972-1974 and 1989-1990. All patients suspected of stroke were clinically evaluated by a neurologist. Only patients with first-ever stroke were included. Complete case ascertainment was ensured by registration of both hospitalized and nonhospitalized patients. Death certificates were also scrutinized. RESULTS: A total of 927 patients with first-ever stroke was recorded. The annual stroke incidence rate per 1,000 increased by 18% from 2.6 in 1972-1974 to 3.1 in 1989-1990 (p < 0.01). This increase was due solely to a 42% increase in men, in whom stroke incidence rose from 2.1 to 3.0 (p < 0.0005). Incidence was unchanged in women at 3.0 and 3.1, respectively. The incidence rates from 1972-1974 were age and sex adjusted to the 1990 population. After adjustment to the Danish population, stroke incidence in Denmark was 2.0 for all, 2.3 for men, and 1.9 for women. In the second study period computed tomography or necropsy was performed in 85% of cases; 2.4/1,000 had cerebral infarction; 0.20/1,000 had intracerebral hemorrhage; and 0.02/1,000 had subarachnoid hemorrhage. CONCLUSIONS: In a period when decline in stroke incidence has stopped in the United States and has continued in Japan, a marked increase of stroke incidence in Danish men was observed. PMID- 1448818 TI - Prevalence and determinants of carotid atherosclerosis in a general population. AB - BACKGROUND AND PURPOSE: The aim of this study was to assess the prevalence of asymptomatic carotid atherosclerotic lesions and their relation to principal risk factors. The importance of the relation between asymptomatic carotid atherosclerotic lesions, stroke, and coronary atherosclerosis has been widely discussed, but there are few transversal and longitudinal studies on a general population. METHODS: A noninvasive examination was carried out using high resolution B-mode ultrasonography, which has been shown to be a reliable tool for epidemiological studies. We examined 630 men and 718 women aged 18-99 years (participation rate, 74.9%). RESULTS: The global prevalence of carotid atherosclerosis was 25.4% in men and 26.4% in women. Intimal-medial thickening was found in 9.4% of men and 11.7% of women. Plaque prevalence was 13.3% in men and 13.4% in women; prevalence of stenotic plaques was 2.7% and 1.5%, respectively. Subjects aged < or = 39 years showed a very low prevalence of any asymptomatic carotid atherosclerotic lesions. In the multiple logistic regression, the analysis of subjects aged > or = 40 years showed a positive significant association between the severity of carotid atherosclerotic lesions (plaques and stenosis) and age (p < 0.001), systolic blood pressure (p < 0.01), cigarette smoking (p < 0.0001), and the protective effect of high density lipoprotein cholesterol (p < 0.037). This analysis did not provide evidence of a clear-cut association between risk factors and intimal-medial thickening. CONCLUSIONS: This population study shows the high prevalence of asymptomatic carotid atherosclerotic lesions in a general population (approximately 25% of adults) and its relation with the classic risk factors. It emphasizes the value of ultrasonography in the detection of early atherosclerotic lesions. PMID- 1448819 TI - Incidence and prognosis of stroke in the Valle d'Aosta, Italy. First-year results of a community-based study. AB - BACKGROUND AND PURPOSE: We sought to determine the incidence rate, risk factors, and prognosis of stroke in Valle d'Aosta, Italy, to provide information for planning regional health-care facilities. METHODS: We undertook a prospective study of all new cases of stroke in the geographically defined population of 114,325 residents of Valle d'Aosta in northern Italy. RESULTS: In the first year of the study (January 1-December 31, 1989), 254 cases of first stroke were registered. The crude annual incidence rate was 2.23/1,000, 1.98/1,000 for men and 2.46/1,000 for women. After adjustment to the 1988 Italian population, the incidence rate for first stroke was 2.15/1,000 per year, 2.48/1,000 per year for men and 1.99/1,000 per year for women. The pathological diagnosis was cerebral infarction in 67%, intracranial hemorrhage in 15%, and unknown in 18%. The overall 30-day case-fatality rate was 31%. In survivors, Barthel Index Score recorded at 30 days from stroke onset showed that 100 patients (62%) were dependent in activities of daily living. CONCLUSIONS: Our results do not differ significantly from those reported in Umbria, the only similar study performed in Italy, and support non-Italian data as to risk factors in stroke. PMID- 1448820 TI - Longitudinal study of regional cerebral blood flow changes in depression after stroke. AB - BACKGROUND: We studied 60 patients longitudinally to examine relations between regional cerebral blood flow and depressive states after stroke. METHODS: Poststroke depressive states were assessed by the Zung Self-Rating Depression Scale (SDS). Regional cerebral blood flow was measured using the 133xenon inhalation method with patients in the resting state on the same day as the SDS assessment. All patients were followed for an average of 14 months after the initial assessment. RESULTS: Severity of depression was inversely correlated with regional cerebral blood flow values in the parieto-occipital regions of the right hemisphere and in the anterior temporal region of the left hemisphere at the initial evaluation. Patients with lesions in left frontal or right parieto occipital regions were more depressive in comparison with those with other brain lesions. Follow-up study showed significant inverse correlations between changes in SDS score and changes in regional cerebral blood flow at all scalp sites. Furthermore, higher inverse correlations were observed at specific brain regions in each hemisphere, including the parietal and parieto-occipital regions of the right hemisphere and the anterior temporal and inferior frontal regions of the left hemisphere. This relation was independent of recovery from neurological deficits. CONCLUSIONS: These results suggest that dysfunction of specific cortical and subcortical regions in both hemispheres asymmetrically contributes to depressive state after stroke. PMID- 1448821 TI - Ticlopidine versus aspirin for the prevention of recurrent stroke. Analysis of patients with minor stroke from the Ticlopidine Aspirin Stroke Study. AB - BACKGROUND AND PURPOSE: Ticlopidine has not been formally compared with aspirin in patients with a completed stroke. We therefore performed an analysis on a subgroup of patients from the Ticlopidine Aspirin Stroke Study (TASS) with a recent minor completed stroke as the qualifying ischemic event. METHODS: This was a multicenter, double-blind, randomized trial of patients with a recent history of cerebral ischemia. Eligible patients had a qualifying minor stroke within 3 months of study entry. All patients received either 650 mg aspirin twice daily or 250 mg ticlopidine twice daily for up to 5.8 years. The primary study end point was the first occurrence of nonfatal stroke or death from any cause. A secondary end point was the first occurrence of a fatal or nonfatal stroke. RESULTS: Minor stroke was the qualifying ischemic event in 927 patients (463 received ticlopidine and 464 received aspirin). The cumulative event rate at 1 year for nonfatal stroke or death was 6.3% for patients receiving ticlopidine and 10.8% for patients receiving aspirin, a 42% risk reduction in favor of ticlopidine. For fatal or nonfatal stroke, the cumulative event rate at 1 year was 4.8% for patients receiving ticlopidine and 7.5% for those receiving aspirin, a risk reduction of 36% for ticlopidine relative to aspirin. The overall risk reductions were 22.1% for nonfatal stroke or death and 19.9% for fatal or nonfatal stroke. Adverse reactions were reported in 58% of the ticlopidine patients and 51% of the aspirin patients. CONCLUSIONS: The results in this subgroup are consistent with the overall TASS results and show that ticlopidine is somewhat more effective than aspirin for reducing the risk of stroke in patients with a completed minor stroke. PMID- 1448822 TI - Cerebral blood flow velocity after hyperventilation-induced vasoconstriction in hypertensive patients. AB - BACKGROUND AND PURPOSE: The aim of our study was to evaluate by transcranial Doppler ultrasonography the dynamics of blood flow velocity changes in the middle cerebral artery during and after hypocapnia-induced vasoconstriction in untreated essential hypertensive patients. METHODS: Sixteen hypertensive patients (10 men and six women, 29-62 years of age) and 10 healthy control subjects (six men and four women, 30-62 years of age) were studied. Patients with mild-to-moderate essential hypertension (mean +/- SE blood pressure, 171/106 +/- 3/2 mm Hg) belonged to stage I or II of the World Health Organization classification. Mean blood flow velocity in the middle cerebral artery, arterial blood pressure, and end-tidal CO2 partial pressure were recorded at baseline, during 2-minute hyperventilation, and every 30 seconds up to 5 minutes after hyperventilation. RESULTS: End-tidal CO2 partial pressure values overlapped in the two groups throughout the study. Baseline values of mean blood flow velocity in hypertensive patients were similar to those in normotensive subjects (mean +/- SE values, 64.7 +/- 3.9 cm/sec versus 58.6 +/- 3.7 cm/sec). A similar fall in mean blood flow velocity was observed in hypertensive patients and normotensive subjects (43.2 +/ 2.8% versus 46.7 +/- 3.6%). Mean blood flow velocity reverted to baseline more quickly in hypertensive patients: 1.5 minutes after hyperventilation, mean blood flow velocity was 60.7 +/- 3.1% and 84.9 +/- 1.8% of control in normotensive subjects and hypertensive patients, respectively. No changes in arterial blood pressure were observed in either group throughout the study. CONCLUSIONS: This study demonstrates that the recovery of blood flow velocity in the middle cerebral artery after hyperventilation is faster in hypertensive patients than in normal subjects, thus providing further evidence that chronic hypertension is associated with changes in the dynamics of cerebral blood vessel reactivity. PMID- 1448824 TI - Critical limits of pressure-flow relation in the human brain. AB - BACKGROUND: This study was designed to determine the minimal mean flow velocity and pressure-flow relation necessary to preserve human consciousness. METHODS: Passive upright tilt provocation was used in conjunction with transcranial Doppler in 80 patients with a history of syncope of unknown etiology. Cerebral blood flow velocity, blood pressure, and heart rate were monitored noninvasively. RESULTS: Forty patients remained asymptomatic, and the rest had clinically induced true syncope or premonitory symptoms. In the asymptomatic group, there was a 23 +/- 16% (p = 0.000) drop in mean flow velocity, but no significant changes in systolic and diastolic blood pressures. In the symptomatic patients, there was a 58 +/- 14% (p = 0.000) drop in mean flow velocity, 37 +/- 23% (p = 0.000) fall in systolic pressure, and 31 +/- 20% (p = 0.000) fall in diastolic pressure. In 80% of symptomatic patients, the critical lower limit of mean flow velocity was at -50% of resting baseline while patients were lying supine. The symptomatic group had lower mean flow velocity and blood pressure responses as compared with the asymptomatic group. The slope and intercept values of the pressure (y axis) to flow velocity (x axis) regression curves indicate a greater degree of impaired autoregulation in the symptomatic group (y = 0.529 x-6.11, r2 = 0.108, p = 0.038) as compared with the asymptomatic (y = 0.317 x + 0.966, r2 = 0.14, p = 0.017). CONCLUSIONS: The critical lower limit of cerebral perfusion lies at 50% below baseline supine mean flow velocity. PMID- 1448823 TI - 99mTc-HMPAO-SPECT with acetazolamide challenge to detect hemodynamic compromise in occlusive cerebrovascular disease. AB - BACKGROUND AND PURPOSE: Insufficiency of collateral supply may lead to low-flow infarcts in severe occlusive cerebrovascular disease. The aim of this study was to evaluate the feasibility of technetium-99m-labeled hexamethylpropyleneamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) to assess hemodynamic compromise in the anterior circulation. METHODS: Cerebral blood flow before and after 1 g acetazolamide was analyzed by 99mTc-HMPAO-SPECT in 21 symptomatic patients with documented extracranial obstructions. SPECT findings were correlated with the results of angiography, transcranial Doppler sonography, and computed tomographic scan. RESULTS: The acetazolamide-induced increase of cerebral blood flow could be reliably monitored by increase of cerebral 99mTc HMPAO uptake, which varied between 11.4% and 47.6% in the less-affected hemisphere. Increment of hemispheric side-to-side asymmetry of tracer uptake after drug challenge revealed significant restriction of regional vasoreactivity in 11 patients. Agreement in assessing hemodynamic compromise was reached in 81% of patients with ophthalmic artery collaterals on angiography (p < 0.001), in 76% with low-flow infarcts on computed tomographic scan (p < 0.01), and in 91% with markedly reduced flow velocities on transcranial Doppler (p < 0.0001). One patient developed a low-flow infarct in the area predicted by SPECT during follow up. CONCLUSIONS: We conclude that 99mTc-HMPAO-SPECT with acetazolamide challenge is a useful method for assessment of the adequacy of hemispheric collateral pathways in patients with severe occlusive cerebrovascular disease. PMID- 1448825 TI - Features on initial computed tomography scan of infarcts with a cardiac source of embolism in the NINDS Stroke Data Bank. AB - BACKGROUND AND PURPOSE: The lack of valid criteria for the clinical diagnosis of cardiogenic embolism is a major problem in both patient care and research. The aim of this study was to identify features on the initial computed tomogram of the brain that discriminate between patient groups with and without a cardiac source of embolism. To gain insight into the neuroradiological features relevant to the diagnosis of cardiac embolic stroke, we studied the initial computed tomogram of the 1,267 patients with ischemic stroke and such a scan in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Data Bank. METHODS: We analyzed the initial computed tomographic data from 1,267 patients with ischemic stroke in the NINDS Stroke Data Bank. Based solely on the presence of cardiac sources of embolism, we defined groups with high (n = 244), medium (n = 165), and low (n = 858) risk for cardiogenic embolism and compared the features on the initial computed tomogram among these three groups. RESULTS: Patients in the high-risk group were significantly more likely (p < 0.001) to have infarcts involving one half lobe or larger or infarcts involving both superficial and deep structures than patients in the medium- or low-risk groups. In contrast, deep small infarcts had a negative association (p = 0.004) with the presence of a cardiac source of embolism. There was no significant trend across risk groups in the percent with hemorrhagic infarction, regardless of whether patients with anticoagulant use at the time of the stroke were excluded. CONCLUSION: Although some features of the initial computed tomogram had highly significant associations with the presence of a cardiac source of embolism, the predictive value of these features for an embolic source was low. PMID- 1448826 TI - Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group. AB - BACKGROUND AND PURPOSE: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged > or = 65 years. METHODS: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged > or = 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history. RESULTS: Detectable carotid stenosis was present in 75% of men and 62% of women, although the prevalence of > or = 50% stenosis was low, 7% in men and 5% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p < 0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation. CONCLUSIONS: In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects. PMID- 1448827 TI - Thrombotic occlusion of the middle cerebral artery. AB - BACKGROUND AND PURPOSE: Epidemiological study of middle cerebral artery occlusion is important because the indication for extracranial-intracranial arterial bypass remains in dispute. To help clarify this issue, we investigated the prognosis of thrombotic middle cerebral artery occlusion in Japanese patients. METHODS: We studied 40 patients with thrombotic middle cerebral artery occlusion who were selected on the basis of clinical features, computed tomographic findings, and angiographic findings. Patients with causes of embolism (i.e., cardiomyopathy, valvular heart disease, cardiac arrhythmia, and carotid ulceration) were excluded. The 40 patients were classified into three groups according to the site of middle cerebral artery occlusion: there were 13 patients with occlusion of the proximal portion of the M1 segment, 13 with distal M1 segment occlusion, and 14 with occlusion of the M2 segment. RESULTS: Good collateral circulation was associated with improved outcomes both clinically and by computed tomography in patients with occlusion of the proximal and distal portions of the M1 segment but not in those with M2 occlusion. CONCLUSIONS: It is reasonable to assume that not only collateral circulation but also the site of occlusion plays an important role in the outcome of middle cerebral artery occlusion. Our finding that good collateral circulation improves the outcome for thrombotic occlusion of the proximal and distal M1 segments supports the possible benefits of such surgery. PMID- 1448828 TI - Arginine vasopressin V1-antagonist and atrial natriuretic peptide reduce hemorrhagic brain edema in rats. AB - BACKGROUND AND PURPOSE: Injection of arginine vasopressin into the cerebral ventricles in animals with brain injury increased brain water, whereas injection of atrial natriuretic peptide reduced water content. Therefore, to determine the role of endogenous arginine vasopressin in brain edema, we attempted to inhibit edema from a hemorrhagic lesion with an arginine vasopressin V1 receptor antagonist or atrial natriuretic peptide. METHODS: Adult Sprague-Dawley rats with hemorrhages induced by 0.4 IU bacterial collagenase were treated with 75 ng (n = 9) or 8 micrograms (n = 9) of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)Arg, 3.2 micrograms (n = 4) atrial natriuretic peptide injected intracerebrally, or 5 micrograms/kg per hour (n = 7) atrial natriuretic peptide intraperitoneally. They were compared with control groups injected with 0.4 IU collagenase only. Brain water and electrolytes were measured 24 hours later. Brain uptake of [14C]sucrose was measured 30 minutes after lesions were induced by 0.4 IU collagenase alone (n = 5) or after collagenase injection and 50 micrograms/kg per hour (n = 5) atrial natriuretic peptide injected intravenously. RESULTS: The arginine vasopressin V1 receptor antagonist and atrial natriuretic peptide significantly (p < 0.05) reduced water and sodium contents in the posterior edematous regions. Brain uptake of [14C]sucrose was significantly reduced by intravenous atrial natriuretic peptide. CONCLUSIONS: Antagonists to arginine vasopressin V1 receptors and atrial natriuretic peptide both significantly reduce hemorrhagic brain edema, and atrial natriuretic peptide appears to protect the blood-brain barrier. PMID- 1448829 TI - Insulin-induced normoglycemia improves ischemic outcome in hyperglycemic rats. AB - BACKGROUND AND PURPOSE: Hyperglycemia is known to aggravate ischemic brain damage. This study sought to determine if preischemic insulin-induced normoglycemia would improve outcome in hyperglycemic rats. METHODS: Normal rats and rats with 5-7 days of streptozotocin-induced diabetes were studied. Normal rats served as either fasted normoglycemic controls or dextrose-infused (hyperglycemic) controls. In the acutely diabetic rats either no insulin was given or insulin was given at 30 or 90 minutes before ischemia so as to induce preischemic normoglycemia. All rats underwent 10 minutes of forebrain ischemia. After 5 days of recovery, motor function and histological outcome were assessed. RESULTS: Untreated diabetic rats and dextrose-infused control rats had greater hippocampal CA1 damage than normoglycemic control rats. In contrast, insulin treated diabetic rats had less hippocampal CA1 damage than either untreated diabetic rats or dextrose-infused control rats. Injury in the two insulin-treated groups was not significantly different from that in the normoglycemic control group (all three groups had plasma glucose values of 120-150 mg/dl immediately prior to ischemia). Despite similar plasma glucose values (300-400 mg/dl), fewer postischemic seizures (0% versus 67%) were observed in the untreated diabetic group than in the dextrose-infused control group (p < 0.001). CONCLUSIONS: Hyperglycemia caused by either dextrose infusion or streptozotocin-induced diabetes resulted in exacerbated ischemic brain damage. Insulin therapy to rapidly induce preischemic normoglycemia improved outcome from forebrain ischemia in the acutely diabetic rats. Glucose-infused hyperglycemic rats frequently exhibited postischemic generalized seizures while acutely diabetic rats did not. The latter results implicate some adaptive/protective mechanism associated with acute streptozotocin-induced diabetes that results in a decreased sensitivity to hyperglycemia-augmented ischemic brain damage. PMID- 1448830 TI - Selective brain cooling during and after prolonged global ischemia reduces cortical damage in rats. AB - BACKGROUND AND PURPOSE: Studies of the cerebroprotective effects of selective brain cooling have failed to show amelioration of ischemic injury in the cerebral cortex. This study was designed to test the hypothesis that mild-to-moderate selective brain cooling initiated after the onset of global brain ischemia in rats protects the cerebral cortex and improves neurological outcome. METHODS: Global forebrain ischemia for 30 minutes in 27 fasted adult male Wistar rats was achieved by bilateral carotid occlusion and hypotension. In group 1, brain temperature, measured in the temporalis muscle, was maintained at 37-38 degrees C throughout the experiment. In group 2, brain temperature fell spontaneously during ischemia to 34.7 +/- 0.1 degrees C and rose spontaneously to 36-37 degrees C after 10 minutes of recirculation. In group 3, brain temperature was lowered with ice packs placed around the head after 15 minutes of ischemia to 24.1 +/- 0.9 degrees C by the end of ischemia, maintained at 30.0 +/- 1.0 degrees C for the first hour of recirculation, then allowed to rise to 36-37 degrees C. RESULTS: Seven-day survival was 0% (0 of 6) in group 1, 73% (8 of 11) in group 2, and 100% (6 of 6) in group 3. Severity of neuronal damage was less in group 2 than in group 1 in the cortex (p < 0.05) and hippocampal CA1 (p < 0.05) and CA3 regions (p < 0.05). Group 3 had less neuronal damage than group 2 in both cortex (p < 0.02) and striatum (p < 0.02). Furthermore, postischemic weight loss was less and neurobehavioral scores were significantly higher in group 3. CONCLUSIONS: This study shows that selective brain cooling increases survival from prolonged global ischemia and reduces neuronal injury in the cerebral cortex as well as the striatum and hippocampus. PMID- 1448831 TI - Antioxidants attenuate microvascular changes in the early phase of experimental pneumococcal meningitis in rats. AB - BACKGROUND AND PURPOSE: We tested in a rat meningitis model 1) whether pneumococcal cell wall components are capable of producing changes in regional cerebral blood flow, brain water content, and intracranial pressure similar to those we have already observed after intracisternal inoculation of live pneumococci and 2) whether antioxidants would modulate these alterations in the early phase of meningitis. METHODS: Regional cerebral blood flow as measured by laser Doppler flowmetry and intracranial pressure were monitored continuously for 4 hours after intracisternal challenge. Brain edema formation was assessed by brain water content determinations. We investigated the following groups: rats challenged intracisternally with the whole intact pneumococcal cell wall (n = 7) or the pneumococcal cell wall hydrolyzed by the M1-muramidase (n = 7); rats injected intracisternally with phosphate-buffered saline (n = 6); rats pretreated intravenously with superoxide dismutase conjugated with polyethylene glycol (10,000 units/kg) and injected intracisternally with cell wall components (n = 5) or phosphate-buffered saline (n = 6); rats injected intracisternally with phosphate-buffered saline and pretreated intravenously with polyethylene glycol (10% solution, 1.2 ml/kg, n = 5) or continuously treated with intravenous free superoxide dismutase (22,000 units/kg per hour, n = 6); and rats continuously treated intravenously with deferoxamine mesylate (10 mg/kg per hour) and injected intracisternally with cell wall components (n = 6) or phosphate-buffered saline (n = 7). RESULTS: Both pneumococcal cell wall preparations produced a significant increase in regional cerebral blood flow, intracranial pressure, and brain water content. Conjugated superoxide dismutase as well as deferoxamine prevented the increase in intracranial pressure and brain water content. In addition, the increase in regional cerebral blood flow as observed in untreated, cell wall challenged rats (baseline, 100%; 183.1 +/- 12.3% after 4 hours, mean +/- SEM) was significantly attenuated by administration of both conjugated superoxide dismutase (136.6 +/- 14.1%) and deferoxamine (149.8 +/- 8.2%) (p < 0.05). Polyethylene glycol-conjugated superoxide dismutase alone produced an increase in regional cerebral blood flow (125.6 +/- 8.7% after 4 hours). We found that polyethylene glycol per se accounts for this action. CONCLUSIONS: These data show that pneumococcal cell wall components containing teichoic acid produce changes in regional cerebral blood flow, intracranial pressure, and brain water content and that oxygen radicals contribute to these pathophysiological alterations in the early phase of experimental pneumococcal meningitis. PMID- 1448832 TI - Effects of retrograde perfusion of the brain with combined drug therapy after focal ischemia in rat brain. AB - BACKGROUND AND PURPOSE: The ischemic edema associated with blood-brain barrier permeability changes and the excess production of free radicals are serious complications in prolonged cerebral ischemia. We examined the efficacy of transvenous perfusion of the brain, starting treatment 5 hours after occlusion of the middle cerebral artery for a period of 2 hours in rats with the combined agents mannitol (10 ml/2 hr) and dexamethasone (1 mg/2 hr) to counter edema and verapamil (0.05 mg/kg/2 hr) for vasodilation. METHODS: In experiment 1, blood brain barrier permeability changes were examined in five groups with six rats each: group C rats underwent 7 hours of middle cerebral artery occlusion with no treatment; group V, treatment with verapamil alone; group VD, treatment with verapamil and dexamethasone; group VM, treatment with verapamil and mannitol; and group VDM, treatment with verapamil, dexamethasone, and mannitol. In experiment 2, we examined local cerebral blood flow, ischemic tissue damage volume, and water content of cerebral hemispheres in two groups of 16 rats each subjected to the same treatment as groups C and VDM rats in experiment 1. RESULTS: There was a significant reduction of blood-brain barrier permeability changes in the ischemic cortex of rats in group VDM compared with rats in the other groups. In the group undergoing transvenous perfusion of the brain with the three combined agents, there was a significant improvement of cerebral blood flow (39-58%, p < 0.05) in the ischemic cortex and reduction of ischemic cerebral damage volume (22%, p < 0.01) and water content of the ischemic hemisphere (p < 0.05) compared with the control group. CONCLUSIONS: The therapeutic approach using combined agents is effective treatment when initiated within 5 hours of focal cerebral ischemia in rats. PMID- 1448833 TI - Spontaneous cerebral hypothermia diminishes focal infarction in rat brain. AB - BACKGROUND AND PURPOSE: Brain temperature during ischemia is known to strongly influence the extent of cellular injury. The objectives of the present study were to determine the effect of severe focal ischemia on brain temperature and to assess the influence of those changes on focal infarction. METHODS: Severe focal ischemia was produced in rats using permanent occlusion of the distal middle cerebral artery combined with transient (60-minute) bilateral carotid artery occlusion. The temperature of the ischemic focus was measured with a small subdural probe. Three groups of rats were studied. In the first group, brain temperature was permitted to decline spontaneously to 32 degrees C after occlusion. In the second, brain temperature was maintained at 37.5 degrees C during occlusion. In the third group, the brain temperature was maintained at 37.5 degrees C for 40 minutes postocclusion before cooling. After recovery for 24 hours, the volume of infarction was measured in histological sections. RESULTS: In the absence of cranial heating, the brain temperature fell to 33 degrees C by 10 minutes postocclusion, and infarct volume was 19 +/- 9 mm3 (mean +/- SEM; n = 6). Maintaining brain temperature at 37.5 degrees C increased the volume of infarction to 82 +/- 16 mm3 (n = 7; p < 0.001). Delayed cooling did not prevent the increase in infarct volume (75 +/- 16 mm3; n = 6). CONCLUSIONS: These results demonstrate that in the present model of transient focal ischemia, spontaneous cooling of the brain during ischemia diminishes the extent of focal infarction, relative to that observed when cerebral hypothermia is prevented or delayed for 40 minutes. PMID- 1448834 TI - Cerebral infarction in a heterozygote with variant antithrombin III. AB - BACKGROUND: We report a heterozygous case of familial qualitative deficiency of antithrombin III associated with cerebral infarction. CASE DESCRIPTION: A 33-year old man had a history of recurrent transient ischemic attacks from the age of 28. Cerebral computed tomography at age 29 disclosed a low-density area in the left frontal lobe, and an internal carotid angiogram showed branch occlusion of the right anterior cerebral artery and stenosis of the left middle cerebral artery. Occlusion of the right middle cerebral artery developed thereafter. The plasma antithrombin III antigen concentration and progressive antithrombin activity were normal, but plasma heparin cofactor activity was low in the patient and his father. Nucleotide sequence analysis of the proband's deoxyribonucleic acid showed no mutation in exons II and VI of antithrombin III. CONCLUSIONS: We conclude that abnormal antithrombin III with defective heparin binding, even though heterozygous, may cause ischemic stroke in young adults. We named this antithrombin III variant "Antithrombin III Nagasaki." PMID- 1448835 TI - Thrombolysis in acute ischemic stroke: does it work? AB - BACKGROUND: This article is presented to provoke further discussion regarding the use of thrombolytic drugs to treat acute ischemic stroke. SUMMARY OF REVIEW: Overview analysis of the six randomized trials of thrombolysis in acute ischemic stroke available in the world literature shows a 20% increase in the odds of death and a 30% reduction in the odds of death or deterioration (both with wide confidence intervals, neither result significant) after thrombolytic treatment for acute ischemic stroke. Exclusion of the two trials conducted without the benefit of computed tomographic scanning shows a 37% reduction in the odds of death (95% confidence interval, 74% reduction to 40% excess) and a significant reduction of 56% in the odds of death or deterioration after thrombolytic treatment (95% confidence interval, 20-76% reduction; 2p = 0.007). Analysis of all published studies (randomized and nonrandomized) shows that there does not appear to be an excess risk of hemorrhagic transformation of the cerebral infarct or of severe edema formation. CONCLUSIONS: We believe the present evidence is sufficiently encouraging to warrant proper testing of thrombolysis in sufficiently large and well-designed randomized clinical trials to influence clinical practice. PMID- 1448836 TI - Evaluation of vasomotor reactivity by transcranial Doppler and acetazolamide test before and after extracranial-intracranial bypass. PMID- 1448837 TI - Applications of transcranial Doppler sonography in acute ischemic stroke. PMID- 1448838 TI - Presumed cardioembolic lacunar infarcts. PMID- 1448839 TI - Prediction of unbound serum valproic acid concentration by using in vivo binding parameters. AB - In a previous study, we determined the in vivo binding parameters of valproic acid (VPA) to serum proteins in seven healthy young adults at steady state by using the Scatchard equation. To evaluate the ability of the Scatchard binding equation to predict steady-state unbound serum VPA concentrations (Cf), 39 adult patients receiving VPA monotherapy and ranging in age from 16 to 68 years were studied. The correlation between predicted and observed Cf was high (r = 0.865). Mean prediction error, mean absolute error (MAE), and root mean squared error (RMSE) were calculated, and served as a measure of prediction bias and precision. The MAE and RMSE were low (MAE = 12.9 mumol/L, RMSE = 17.7 mumol/L). It is feasible to use the Scatchard binding equation to predict Cf in patients receiving VPA monotherapy. PMID- 1448840 TI - Ability of three pharmacokinetic equations to predict steady-state serum theophylline concentrations in pediatric patients. AB - The pharmacokinetic equations of Chiou, Koup, and Kurland are often used in the pediatric setting to predict steady-state theophylline clearance using non-steady serum theophylline concentrations. However, these equations have not been validated or compared in a pediatric population. We evaluated the ability of these equations to predict steady-state serum theophylline concentrations in 61 children (0.21-14.3 years) who received a continuous intravenous theophylline (0.79 +/- 0.12 mg/kg/h) infusion for a minimum of five half-lives. Theophylline concentrations used in the Kurland equation were obtained 10.8 +/- 4.5 h after initiation of therapy and the time between the two concentrations used in the Chiou and Koup equations was 9.2 +/- 3.9 h. Predicted steady-state theophylline concentration values for the three methods were not different from each other (p = 0.91), nor were they different from the observed steady-state concentration values (p = 0.92). The coefficient of determination for predicted vs. observed steady-state concentrations was statistically significant (p less than 0.001) and was comparable for the three methods. There was no difference in mean bias (p = 0.78), precision (p = 0.82), or % error (p = 0.86) values for the three methods. Regardless of the method used, 75 to 82% of all predicted theophylline concentrations were within 20% of the observed steady-state value. However, on average, all methods underpredicted the clearance and hence overpredicted the serum theophylline concentration. The Kurland method did not predict steady-state concentrations any better in patients who had received theophylline prior to admission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448841 TI - Altered heparin pharmacodynamics in patients with pulmonary embolism. AB - Heparin clearance and pharmacodynamic response were examined in 12 patients being treated for deep venous thrombosis (DVT, 6 patients) or pulmonary embolism (PE, 6 patients). A loading dose of 70 units/kg was administered to DVT patients and 100 units/kg to PE patients followed by an initial infusion rate of 15 or 25 units/kg/h for DVT or PE patients, respectively. Heparin clearance was determined at 4, 12, and 24 h after initiating heparin therapy. The mean heparin clearance in the DVT group was 2,164 +/- 1,024 ml/h at 4 h, 2,591 +/- 1,239 ml/h at 12 h, and 2,795 +/- 1,863 m/h at 24 h. The PE patients had clearances of 1,775 +/- 494, 2,004 +/- 321, and 2,843 +/- 1,000 ml/h at 4, 12, and 24 h, respectively. The difference between the two groups was not statistically significant (p greater than 0.50). The activated partial thromboplastin time (aPTT) was used as a measure of heparin effect. The maximum effect (EMAX) and concentration required to attain 50% of the maximum effect (EC50) were determined for each group using the Lineweaver-Burke linearization method. The mean EMAX and EC50 for the DVT patients were 130 +/- 40.99 s and 1.01 +/- 0.70 units/ml, respectively. For the PE patients, the mean EMAX was 418 +/- 200 s and the mean EC50 was 4.32 +/- 2.81 units/ml. The difference between both groups for each parameter was statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448842 TI - Preliminary studies on the in vitro and in vivo effect of salicylate on sperm motility. AB - We have studied the in vitro effect of different concentrations of salicylic acid on the motility of normal human spermatozoa. Sperm motility was evaluated over 48 h at 0, 50, 100, and 200 mg/L of salicylate concentrations. Results are reported as the mean % motility, where 100% motility at each time interval was taken to be the motility of the control (0 mg/L of salicylate). At 48 h, the mean % motility (n = 12) was 61, 43, and 33% at 50, 100, and 200 mg/L of salicylate. Twenty-four hour values (n = 17) were 75, 65, and 48%. Eosin supravital staining demonstrated that the decrease in sperm motility was caused by direct inhibition of motility rather than by spermatozoal death. Four healthy males (17-51 years of age) gave a semen specimen prior to taking 650 mg of salicylate four times daily, followed by a second semen specimen 72 h later. Each individual, therefore, served as his own control. The mean % motility in the postdrug sample at 2, 24, and 48 h was 49, 53, and 47% of the motility found in the predrug sample (n = 4). We conclude that salicylate significantly decreases sperm motility in vitro and in vivo. PMID- 1448843 TI - Pattern of 6-mercaptopurine urinary excretion in children with acute lymphoblastic leukemia: urinary assays as a measure of drug compliance. AB - A method for the measurement of 6-mercaptopurine (6MP) in urine using high performance liquid chromatography is described. Urinary excretion of 6MP was measured in 46 children with acute lymphoblastic leukemia. The proportion of unchanged drug excreted after oral dosage in the morning was greater than after an evening dose (5.6 +/- 3.3% vs. 3.3 +/- 2.4%). Possible reasons for the discrepancy are discussed. In all children receiving 6MP in the morning, the drug was detected in urine at 2 and 4 h after ingestion. At 6 h, 6MP was still detectable in 77% of patients, at 8 h in 54%, at 10 h in 12%, and at 12 h in 8%. The reliability of urinary 6MP determination as a measure of drug compliance was assessed in 39 children accustomed to receiving their medication in the evening. 6MP was detected in 81% of first morning urine samples, indicating compliance with medication the preceding evening. The absence of 6MP in first morning urine samples did not necessarily indicate poor compliance because of the variability in 6MP excretion and unpredictable pattern of night voiding in children. The method was therefore a reliable measure of good short-term compliance. It also directed attention toward possible noncompliance in children with negative samples. PMID- 1448844 TI - Changes in unbound and total valproic acid concentrations after replacement of carbamazepine with oxcarbazepine. AB - Total and free valproic acid (VPA) concentrations were measured in patients switched from a combined VPA and carbamazepine (CBZ) to a combined VPA and oxcarbazepine (OXC) therapy, both administered in individualized daily doses. Four young epileptic patients (13-17 years old) were studied for a 12-week period, total and free VPA concentrations being analyzed just before and 4 h after the morning dose, at the end of VPA and CBZ therapy, and 2 and 10 weeks after CBZ was replaced by OXC. The expected increase in the level/dose (L/D) ratio of total VPA observed at the end of the study was preceded by a clear-cut increase in the L/D ratio of free VPA, which led to VPA-related side effects and required the retitration of VPA daily doses. PMID- 1448845 TI - Plasma levels of trimipramine and metabolites in four patients: determination of the enantiomer concentrations of the hydroxy metabolites. AB - A two-step high-performance liquid chromatography method is described, using a CN column and an alpha 1-acid glycoprotein column, which allows the measurement of the enantiomers of the hydroxy metabolites of trimipramine in plasma of trimipramine-treated patients. Of the four patients analyzed, three showed approximately equimolar concentrations of the (D)- and (L)-enantiomers of the hydroxy metabolites (2-hydroxy-trimipramine and 2-hydroxy desmethyltrimipramine), and one was found to have roughly twice as much of the (L)-form and of the (D) form of 2-hydroxy trimipramine and 2-hydroxy desmethyltrimipramine. From the data available on the pharmacological effects of the enantiomers of trimipramine, it is postulated that this interindividual variability in its pharmacokinetics is another factor that could contribute to the interindividual variability in its pharmacodynamics. PMID- 1448846 TI - Measurement of phenytoin in serum using in-house reagents employing the Syva enzyme-multiplied immunoassay technique principle. AB - Reagents have been developed for the measurement of phenytoin in serum, using the enzyme-multiplied immunoassay approach first introduced by Syva. The assay uses a commercially available antiserum and phenytoin valeric acid coupled to glucose-6 phosphate dehydrogenase as the tracer. It has been adapted for use on an Eppendorf EPOS analyser, which allows 300 assays/h with high precision. Excellent agreement was achieved with commercial reagents, and costs were reduced markedly. PMID- 1448847 TI - Determination of lorajmine and its metabolite ajmaline in plasma and urine by a new high-performance liquid chromatographic method. AB - Lorajmine is a monochloroacetyl derivative of ajmaline with electrophysiological properties somewhat different from those of the compound of origin. Since lorajmine is rapidly hydrolyzed to ajmaline by plasma and tissue esterases, it is crucial to measure plasma levels of both drugs separately. A major problem in assaying lorajmine is its chemical instability in plasma both after blood sampling and during the extraction procedure. Furthermore, lorajmine (unlike ajmaline) is not fluorescent and has a very low UV absorbance, so the standard detectors for high-performance liquid chromatography cannot be used. We describe a new method that solves the problems of instability and sensitivity. Plasma esterases are first blocked pharmacologically (neostigmine); ajmaline is then measured by direct on-column injection of samples. Last, lorajmine is completely converted to ajmaline, extracted, and measured with a fluorescence detector. The molar concentration of ajmaline obtained in the last step, minus that found by direct injection, gives the concentration of lorajmine. Some examples of pharmacokinetic applications are also given. PMID- 1448848 TI - High-performance liquid chromatographic analysis of cyclosporin G (Nva2 cyclosporine) in human blood. AB - A sensitive high-performance liquid chromatographic method for the analysis of the immunosuppressant cyclosporin G (OG 37-325, Nva2-cyclosporine, CsG) in whole blood has been developed. Sample preparation, employing cyclosporin A (CsA) as internal standard, involves organic extraction with methyl t-butyl ether under sequential acidic and basic conditions. Chromatography is performed using a 2 mm inside diameter x 25 cm column packed with 5 microns octyl (C8) material. An isocratic mobile phase comprised of acetonitrile:methanol:water, at a flow rate of 0.4 ml/min, is utilized. Separation is monitored at 230 nm. Data are also presented that demonstrate the use of CsG as an alternative internal standard to cyclosporin D for liquid chromatographic determinations of CsA. PMID- 1448849 TI - Determination of dextromethorphan and its O-demethylated metabolite from urine. AB - A high-performance liquid chromatography (HPLC) assay for the simultaneous quantitation of dextromethorphan and its O-demethylated metabolite dextrorphan from urine is described. A cyano analytical column was used with a mobile phase consisting of MeOH 16%, acetonitrile 3%, and triethylamine 0.06% at pH 2.8 and a flow rate of 1.0 ml/min. Betaxolol was used as the internal standard. Standard curves from 50 ng/ml to 10,000 ng/ml (dextrorphan), and from 50 ng/ml to 8,000 ng/ml (dextromethorphan) were developed. The peaks eluted at 7.8 min (dextrorphan), 12.2 min (betaxolol), and 17.8 min (dextromethorphan). The coefficients of variance ranged from 1.3 to 4.5% at 250 ng/ml and 0.9 to 2.5% at 5,000 ng/ml. This assay was used to determine dextromethorphan/dextrorphan molar ratios in healthy male volunteers for the purpose of determining phenotype status for the P450IID6 isozyme. PMID- 1448850 TI - Application of the Empore solid-phase extraction membrane to the isolation of drugs from blood: II. Mexiletine and flecainide. AB - A stabilized therapeutic drug monitoring procedure incorporating the novel Empore solid-phase extraction membrane (SPEM) for isolation of the antiarrhythmic drugs mexiletine (MEX) and flecainide (FLEC) from serum is described. Routinely, serum (0.5 ml), adjusted to pH 4.5, is passed through an octyl (C8) SPEM to extract the drugs. A methanol:water wash follows to remove proteins and interferences. MEX and FLEC are eluted from the membrane with mobile phase and an aliquot is injected directly onto a Zorbax cyanopropyl (CN) high-performance liquid chromatographic column with detection at 214 nm. Evaporating/concentrating techniques that can adversely influence the stability of the volatile MEX are unnecessary. Recovery for both drugs exceeds 90% and the assay is linear from 0.05 mg/L up to at least 6.0 mg/L for MEX and from 0.05 mg/L up to at least 3.0 mg/L for FLEC. Precision (between-run) coefficients of variation range from 2.3 to 3.0% (0.49-1.97 mg/L) for MEX and 3.7 to 5.9% (0.240-0.992 mg/L) for FLEC. Interferences are minimal. When we compared performance of the Empore SPEM and large-particle solid-phase sorbents packed in cartridges, we observed greater capacity per gram of sorbent and smaller elution volume with the membrane. Most important, concentrating steps that adversely affect the stability of MEX are avoided with the SPEM. PMID- 1448851 TI - Relationship between serum concentration and dose of valproic acid during monotherapy in adult outpatients. AB - The relationship between serum concentration and dose of valproic acid (VPA) is reported to be variable and inconsistent. However, studies evaluating this relationship have included individuals of varying ages and patients receiving potentially interacting medications. In this study, the relationship between VPA serum concentration and dose was evaluated in a homogeneous patient population. Medical records of 60 adult outpatients with epilepsy receiving VPA monotherapy were examined retrospectively for VPA dose (milligrams per kilogram) and corresponding serum VPA concentrations. A significant linear correlation was found in the relationship between VPA dose and serum concentration among all patients (r = 0.63; p less than 0.01). However, considerable interindividual variability in this ratio was demonstrated [coefficient of variation (CV) = 28.9%], and the ratio was significantly dependent on VPA dose. In three selected individual patients, a significant linear correlation was also demonstrated in the VPA serum concentration:dose relationship over time (r = 0.91, 0.94, 0.96; p less than 0.05 for all three patients) with substantially less variability (CV = 10.2-14.6%) and without significant dose dependency, suggesting that this parameter may be useful for guiding VPA dosage adjustment and monitoring patient compliance. Further study is required to evaluate the utility of the serum concentration:dose ratio in monitoring VPA therapy. PMID- 1448852 TI - Evaluation of instrumental, nonisotopic immunoassays (fluorescence polarization immunoassay and enzyme-multiplied immunoassay technique) for cyclosporine monitoring in whole blood after kidney and liver transplantation. AB - Two new instrumental methods, an enzyme-multiplied immunoassay technique (EMIT) and a fluorescence polarization immunoassay (FPIA), were evaluated for monitoring of cyclosporine (CyA) in whole blood samples of renal and liver transplant patients. They are considered as being specific to the parent drug and they were compared with a specific radioimmunoassay (RIA) and a nonspecific FPIA. The data reveal that the novel procedures provide slightly overestimated CyA levels compared with specific RIA (6-12% for EMIT, 20-25% for FPIA). For both assays, intrarun and interrun reproducibilities were found to be in the 2-8% range. The ease of performance and the possibility of performing approximately 40 assays/h make the two methodologies very attractive for both routine and emergency analyses. These approaches are viewed to be complementary to the only previously available instrumental method, the nonspecific FPIA, which provides three- to fourfold higher CyA levels than those obtained with specific methods. Specific and nonspecific monitoring of CyA levels allowed variations in proportions of metabolites to total CyA and metabolites to be distinguished. A higher percentage and variability of cross-reacting metabolites were found in whole blood samples after liver transplantation compared with those in blood of kidney transplant recipients. PMID- 1448853 TI - Gas chromatography/mass spectrometry validation of high-performance liquid chromatography analysis of flecainide enantiomers in serum. PMID- 1448854 TI - [The diagnostic value of medical examinations and their use: external validity]. PMID- 1448855 TI - [How to treat epilepsy in children?]. PMID- 1448856 TI - [Dysplastic valvular regurgitations]. PMID- 1448857 TI - [Neoplastic pericarditis: clinical and anatomo-pathologic aspects. 14 case reports]. PMID- 1448858 TI - [Malabsorption syndromes and immunoglobulin deficiencies]. PMID- 1448859 TI - [Importance of the determination of free thyroxine in comparison with total thyroxine in thyroid disease diagnosis]. PMID- 1448860 TI - [Glucocorticoids and psychiatry]. PMID- 1448861 TI - [The importance of functional cerebral imaging in psychiatric pathology]. PMID- 1448862 TI - [Bourneville's tuberous sclerosis: computed tomography study]. PMID- 1448863 TI - [Caroli's disease in children. Literature review. Two case reports]. PMID- 1448864 TI - [Dermoid mesenteric cysts: a case simulating a dermoid cyst of the ovary]. PMID- 1448865 TI - [Effect of Fusarium autolysate on various immunologic and biologic indices of the state of the carp body]. AB - The Fusarium autolysate has been studied for its effect on certain immunobiochemical, parasitological and fishery-biological characteristics of carp fingerlings in the experiment. It is shown that different methods of introduction and treatment of fish with the autolysate induce changes in titres of the compliment and the content of lysozyme in the blood serum of fish as well as growth of its body weight. Treatment of carp spawn before its incubation increases survivability of fish. It is shown advisable to apply the autolysate in food fishery. PMID- 1448866 TI - [Riboflavin metabolism in diabetes mellitus]. AB - Riboflavin excretion with urine in children suffering from diabetes mellitus is found to be significantly higher in comparison with healthy adults, the riboflavin content in the serum being normal. The total riboflavin concentration in erythrocytes is substantially lower and administration of daily-required riboflavin doses does not increase this parameter. FAD-dependent glutathione reductase in erythrocyte hemolysates is approximately 1.5 times higher than that of healthy children and does not depend on the additional intake of polyvitamins. The seeming affinity of the enzyme with exogenous FAD in sick children is almost 40 times lower in comparison with this value in healthy children, that is why the FAD-effect value in diabetes mellitus children does not exceed 1.2. Peculiarities of the riboflavin metabolism at diabetes mellitus and possibility to use the investigated parameters as criteria of vitamin B2 supply are discussed. PMID- 1448867 TI - [Methemoglobin-induced lipid peroxidation in model membranes]. AB - Lipid peroxidation induced by methemoglobin in liposomes prepared from lecithin, cardiolipin and their mixtures has been investigated. Using absorption spectroscopy technique it was shown that in the bilayers with low initial oxidation methemoglobin caused the formation of diene conjugates. In the bilayers with high degree of oxidation protein activated cleavage of the available fatty acid hydroperoxides. Hydroperoxides were found to induce the reduction of methemoglobin absorption in the Soret band. PMID- 1448869 TI - [A model of intra- and intermolecular interactions of peptide chains]. AB - Results of attempts to determine the code of interaction of amino acids in peptide chains proceeding from their coding nucleotide sequences have been summarized. According to the model suggested the G/C and A/U complementarity of codon roots determines the mutual binding of coded amino acid residues. Structures of analogs of the immunoactive peptide, a fragment of IgG1 (336-370) EPQVY have been constructed on the basis of the model. PMID- 1448868 TI - [Change in the intensity of biosynthesis of proteins, lipids and glycogen in animal tissues during long-term administration of morphine]. AB - The intensity of biosynthesis processes in animal organism has been studied as affected by long-term administration of morphine. It was established that morphine administration to rats for five weeks intensified protein biosynthesis in the brain, kidneys, skeletal muscles: specific radioactivity of blood serum proteins also increased. Incorporation of 2-/14C/glycine label to the brain, cardiac and skeletal muscles increased as affected by morphine: the label incorporation to the liver lipids decreased and that to the kidney and spleen lipids did not change. Specific radioactivity of glycogen multiply increased in the rat liver as affected by morphine. PMID- 1448870 TI - [Interaction of melittin with a model membrane in the presence of antibodies]. AB - The method of fluorescence spectrofluorimetry has been applied to study the interaction of melittin at high and low ionic strength with the phosphatidylcholine model membrane in the presence of monospecific polyclonal and monoclonal antibodies against this peptide. The formation of antigen-antibody complex with the excess of the antigen is shown to decrease the leakage of calcein, a fluorescence dye. With the excess of antibodies the dye leakage is completely suppressed. This effect does not depend on the state of peptide aggregation before binding to the membrane. It is suggested that melittin antigenic determinants are located on the sites of peptide molecule which are necessary for its interaction with the membrane. PMID- 1448871 TI - The charge and atherogenicity of low density lipoproteins. AB - It is concluded on the basis of literature data, that apolipoprotein B-100 is the most high-molecular, hydrophobic, and positive charged protein compared to the other apoproteins of the plasma lipoproteins. Low density lipoproteins of healthy subjects, mainly containing apo B-100, have little heterogeneity on both charge and isoelectric point, in spite of heterogeneity on sizes and apolipoprotein composition. The reason of formation of subfraction with elevated negative charge is the damage with the free radicals and/or aldehydes. The reason of formation of more cationized subfraction is unclear. LDL charge changes are noted in some diseases and syndromes (ischemic heart diseases, familial hyper-alpha lipoproteinemia, Tangier disease, X-bound ichthyosis and, possibly, others). Some IHD patients treatment with antioxidants leads to the disappearance of negative charged LDL subfraction, that shows participation of peroxidation products in their formation. Electrical characteristics of LDL of tissue fluids and of aorta wall differ essentially from those of the same class plasma lipoproteins. Lipid peroxidation and influences of several enzymes play the main role in these differences. PMID- 1448872 TI - [Catalytic effect of gamma-thrombin on synthetic low molecular weight peptide substrates]. AB - Hydrolysis and respective catalytic parameters of hydrolysis of ester peptide substrates that contain residues of hydrophobic and nonpolar amino acids in P2, P3 subsites have been studied. It is shown that efficiency of hydrolysis by thrombin is determined by the length of polypeptide chains and by the nature of the amino acids in P2, P3 subsites in the substrate. In spite of the fact that gamma-thrombin retains the conformation activity of the catalytic centre the local conformation changes of the second binding region of the enzyme have been discovered. PMID- 1448873 TI - [Effect of low doses of external and internal ionizing radiation on proteinases of cells in the rat cerebral cortex of rats]. AB - Single external gamma-irradiation in a dose of 0.5-2 Gy as well as the long-term (30 days) internal irradiation caused by the everyday influx of Cs-137 and Sr-85 isotopes to the organism have been studied for their effect on the activity and properties of histone-specific proteinase from the nuclei of the rat brain cortex cells. It is found out that external irradiation induces a dose-dependent increase of the activity during the first 24 hours after irradiation followed by its decrease 7-30 days later. Internal irradiation induces a decrease of the enzyme activity at the 30th day as well. Certain specificity of the studied indices depending on the type of irradiation has been also observed. PMID- 1448874 TI - [High density lipoproteins of the human aortic wall; size distribution]. AB - The paper presents data on distribution of human aortic high density lipoproteins (A-HDL) according to their size. A-HDL were isolated from the aortic intima (autopsy material) and analyzed by the gradient gel electrophoresis method. The obtained data show that the clear-cut difference exists between size distribution of A-HDL from patients whose death was connected with atherosclerosis and those who died from the diseases not connected with atherosclerosis. In the first case small particles (HDL3B and HDL3C) were predominant. A-HDL with size corresponding to plasma HDL2A and HDL2B slightly predominated in normal intima and A-HDL with size of plasma HDL3A and HDL3C predominated in affected parts of intima. The principal component analysis of data permits suggesting that one of the factors responsible for the accumulation of small A-HDL is a decreased permeability of the affected parts of the vessel wall for the larger HDL particles. Besides, changes of the normal HDL metabolism can also be responsible for the presence of small HDL particles in the intima. PMID- 1448875 TI - [High density lipoproteins in the blood of rats of varying age]. AB - The study revealed age-related changes in the content and ratio of apoproteins which are part of high-density lipoproteins (HDL), as well as the development of dysapolipoproteinemia. The most significant fall (by 46.7%) was found in the content of the key HDL apoprotein--apoA1, and rise (by 107%)--in apoE. The development of dysapolipoproteinemia was accompanied by changes in the lipid composition of HDL and their subfractions (HDL2 and HDL3). HDLs were enriched by cholesterol and its esters. HDL cholesterol/apoA1 ratio increased twice, while the content of phospholipids decreased. PMID- 1448876 TI - [Effect of phytoecdysteroids and nerobol on parameters of carbohydrate and lipid metabolism and phospholipid spectrum of liver mitochondrial membrane in experimental diabetes mellitus of rats]. AB - Phytoecdysteroids: ecdysterone and turkesterone, introduced orally to male rats with the body mass 180-120 g in a dose of 5 mg/l kg of mass and nerobol in a dose of 10 mg per 1 kg of the mass for 15 days against a background of the developed alloxan diabetes cause a considerable decrease in the content of free fatty acids of the blood serum, sharply increased after the subcutaneous injection of alloxan to the animals (150 mg per 1 kg of the mass). The content of glycogen, malonic dialdehyde, pyruvic acid and calcium transporting function of the liver mitochondria are also normalized. These changes are closely interrelated (and may be mutually conditioned) with the preparation-induced reduction of phospholipid spectrum of the liver mitochondrial membranes pathologically changed owing to insulin insufficiency. In this case phytoecdysteroids in the first turn normalize the fractions of phospholipids which play the structural role in the mitochondrial membranes, and nerobol normalizes the level of minor and monoacylic phospholipids. PMID- 1448877 TI - [Ligand spectrum of hemoglobin activity of methemoglobin-reductase and hemolytic resistance of erythrocytes during chronic exposure to nitrates]. AB - It is found that nitrite-ions formed as a result of biotransformation during long term feeding of calves with sodium and potassium nitrates induce changes in some biochemical parameters of blood, including HS-glutathione content in erythrocytes, acid hemolytic resistance of erythrocytes, activity of NAD dependent methemoglobin-reductase, correlation of ligand forms of hemoglobin and its total content. It is supposed that the observed changes are of an adaptational character and, as a whole, provide for the optimization of both quantitative and qualitative composition of population of erythroid cells at the expense of erythropoiesis intensification. PMID- 1448879 TI - [Structural organization of the monofilamentary protofibrils and their association into fibrils]. AB - Evidence of the fibrinogen molecule structure which is suggestive of an antiparallel arrangement of polymerization sites is summarized. A three dimensional model of the structural organization of a monofilamentary protofibril is proposed. A possible role of the "A" and "a" polymerization centers in the lateral association of protofibrils is contemplated. The formation of fibrils in a form of a hollow cylinder is postulated. PMID- 1448878 TI - [Functional and diagnostic significance of A-, Bbeta 1-42 and Bbeta 15-42 peptide fragments of fibrin(ogen)]. AB - A scheme of in vitro formation and hydrolysis of the fibrin clot is suggested. This scheme considers the data concerning a cofactor role of fibrin in activation of polymerization and fibrinolysis. Such parameters of a number of components as concentration of A-, B beta 1-42-and B beta 15-42 peptides and of other fragments of fibrinogen which allow characterizing a state of hyperfibrinolysis, hyperclotting or dynamic equilibrium of these systems are selected in the scheme. PMID- 1448880 TI - [Effect of nitrobenzoic acid on methemoglobin content in blood and activity of antioxidative enzymes in erythrocytes]. AB - Intraperitoneal administration of meta-nitrobenzoic, 3,5-dinitrobenzoic, 2,4,6 trinitrobenzoic and 3,5-dinitro-4-methylbenzoic acids to the white mice in a dose equal to LD50 has induced an increase in the methaemoglobin content in their blood. Total activity of dehydrogenases of pentosephosphate pathway, content of 2,3-diphosphoglycerate increase in response to the intoxication evoked by the mentioned acids. The acute intoxication does not practically change the activity of the key enzymes of antioxidant protection: superoxide-dismutase, catalase and glutathione peroxidase. PMID- 1448881 TI - Correlative study of adult respiratory distress syndrome by light, scanning, and transmission electron microscopy. AB - The sequential pulmonary changes occurring in the evolution of adult respiratory distress syndrome (ARDS) were studied in 35 patients by correlative light, scanning, and transmission electron microscopy. The causes of ARDS were diverse, the major ones being sepsis or aspiration. Patient survival ranged from 3 to 51 days. The acute stage in patients surviving 2 to 7 days was characterized by an exudative reaction with a predominance of hyaline membranes. This acute stage merged with and was replaced by a subacute reparative stage in patients surviving 7 to 14 days, which in turn was replaced by a chronic fibroproliferative stage complicated by interstitial pulmonary fibrosis and a deranged acinar architecture. Correlation of findings by scanning electron microscopy with those by light and transmission electron microscopy provided an added dimension to understanding of the evolving stages of ARDS and demonstrated that type 2 pneumocytes contributed to the fibroproliferative stage through organization of hyaline membranes and re-epithelialization of alveoli. PMID- 1448882 TI - Immunohistochemical and electron microscopic profiles of cutaneous Kaposi's sarcoma and bacillary angiomatosis. AB - Thirty cases of cutaneous Kaposi's sarcoma (KS) were evaluated and compared with eight cases of acquired immunodeficiency syndrome (AIDS)-related bacillary angiomatosis (BA). The morphologic features of both lesions were studied by light and electron microscopy and by immunohistochemistry with monoclonal endothelial antibodies against CD34, BNH9, and factor VIII-related antigen as well as the lectins Ulex europaeus 1 and Psophocarpus tetragonolobus. Macrophage/monocyte markers used were alpha 1-antitrypsin, lysosome, Kp1 (CD68), and polyclonal factor XIIIa. Electron microscopic studies demonstrated that most of the spindle cells in KS showed a paucity of cell organelles and an absence of Weibel-Palade bodies (WPB), whereas the cells in BA showed activated endothelial cells with WPB. By immunohistochemistry the spindle cells in KS were consistently positive for CD34 only, whereas proliferating cells in BA expressed all endothelial markers used. Numerous cells expressing macrophage/monocyte markers were present surrounding both KS and BA, and a small number of similar cells were entrapped within both lesions. The results demonstrated a restricted immunohistochemical profile for endothelial cell markers in spindle cells of KS (CD34+) distinct from that of endothelial cells in BA. These findings suggest that the spindle cells in KS are poorly differentiated endothelial cells or that they belong to an endothelial cell subset with partial expression of endothelial phenotype. PMID- 1448883 TI - Membranocystic lesion in sclerosing lipogranuloma of the scrotum: an ultrastructural study. AB - Two cases of intrascrotal sclerosing lipogranuloma are reported in which affected adipose tissues showed peculiar membranocystic lesions (MCL) similar to the features described in Nasu-Hakola disease. On light microscopy, the MCL were seen in the degenerative fatty tissues and within multinucleated giant cells, which were positive for periodic acid-Schiff stain and resistant to diastase digestion. Ultrastructurally, two types of MCL were observed; one type was characterized by thick membranes composed of vesicular to minute tubular or fibrillar substructures, and the other type was characterized by thin membranes composed of only small numbers of tiny vesicles. The substructures in both types of MCL contained lipid droplets similar to those in the inner space. These results support the concept that the membranes in the MCL are derived from degenerated fat droplets. PMID- 1448884 TI - Ultrastructure and immunohistochemistry of a fetal-type Leydig cell tumor. AB - A symptomless scrotal mass was removed from a 34-year-old man. The lesion was 7 cm in diameter and it was grossly a hemorrhagic cyst with indurated walls. By light microscopy tumor cell clusters and cords were seen infiltrating the testicle, tunica albuginea, and paratesticular tissue. In the immunohistochemical analysis the tumor cells were immunoreactive with anti-S-100 protein and anticarcinoembryonic antigen, but they did not express cytokeratin or alpha fetoprotein as tested with paraffin sections. Tumor cell clusters were enveloped by a laminin-positive basement membrane. Electron microscopy revealed abundant smooth endoplasmic reticulum, lipid droplets, and membranous whorls in the cytoplasm. Lamellar whorled bodies were also seen in mitochondria, which contained tubulovesicular cristae. The presence of a well-developed, often multilayered basement membrane was confirmed at ultrastructural level. The activity of 3-beta-hydroxysteroid dehydrogenase suggested that the tumor cells were capable of androgen synthesis. The morphological features are reminiscent of fetal-type Leydig cells and are distinctly different from the Leydig cell tumors described so far. PMID- 1448885 TI - Solid and papillary neoplasm of the pancreas. AB - In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well as zymogenlike granules were demonstrated. Measurements of mean nuclear volume and volume-corrected mitotic index discriminated between SPN and well-differentiated ductal adenocarcinoma of the pancreas, with notably lower values being seen in SPN. Silver-stained nucleolar organizer region counts showed wide overlaps. The results suggest that SPN is a tumor with mixed endocrine and exocrine features. Its low malignant potential compared to ductal adenocarcinoma is reflected in the mean nuclear volume and volume-corrected mitotic index. The presence of estrogen receptors may prove therapeutically useful. PMID- 1448886 TI - Ultrastructural and immunocytochemical study of a primary gastrinoma of the liver. AB - A primary hepatic gastrinoma found in a 13-year-old boy was studied by light microscopy, immunohistochemistry, electron microscopy, and immunoelectron microscopy. Results were consistent with a neuroendocrine neoplasm with abundant gastrin-immunoreactive cells. Unlike all previously reported cases of primary hepatic neuroendocrine tumors, which have been endocrinologically asymptomatic, the patient had a Zollinger-Ellison syndrome apparently cured by surgical resection of the tumor. PMID- 1448887 TI - Pigmented intracerebral neuroepithelial cyst: report of a case. AB - A 35-year-old man with seizure disorder was found to have a parietal lobe neuroepithelial cyst. The lining of the cyst was made up of ependymal cells containing neuromelanin, which was confirmed ultrastructurally. This appears to be the first report of a pigmented neuroepithelial cyst in the brain parenchyma. PMID- 1448888 TI - Case for the panel. Detection of oligocilia arising from smooth muscle cells of leiomyosarcoma and bilharzial ureters. PMID- 1448889 TI - Two-dimensional arrays for medical ultrasound. AB - The design, fabrication and evaluation of two-dimensional transducer arrays are described for medical ultrasound imaging. A 4 x 32, 2.8 MHz array was developed to use new signal processing techniques for improved B-scan imaging including elevation focusing, phase correction and synthetic aperture imaging. Laboratory measurements from typical array elements showed 50 omega insertion loss of -56 dB, -6 dB fractional bandwidth of 43%, interelement crosstalk of -19 dB, and -6 dB pulse-echo angular response of 62 degrees. Simulations of pulse-echo beam plots have shown grating lobes 20 dB below the main lobe at +/- 7 degrees in the elevation direction. The complete 2-D array has been used for measurements of phase aberrations in breast, and the individual 32 element linear arrays have been used to obtain conventional B-scans. Several 16 x 16 arrays have also been developed for high speed volumetric imaging. These include 96 transmit elements and 32 receive channels. With a lambda/4 matching layer, laboratory measurements show 50 omega insertion loss of -72 dB, -6 dB fractional bandwidth of 63%, interelement crosstalk of -29 dB and -6 dB angular response of 25 degrees. Pulse echo sensitivity was improved by 21 dB through the use of integrated circuit preamplifiers of high impedance mounted in the transducer handle. In vivo cardiac, abdominal, and obstetric B-scans with elevation focusing, as well as high speed C-scans, have been obtained with these 2-D arrays. PMID- 1448890 TI - In vivo imaging using a copolymer phased array. AB - Phased-array images have been obtained in vivo with a steered copolymer array operating at 2.5 MHz. The array was fabricated using 28 microns copolymer film, lambda/4 resonant at 21 MHz, which was bonded to a glass ceramic backing with a thin film bond. The 32 array elements were created by laser ablation of the continuous gold electrode on one side of the film. The transducer was driven by 200 V shock excitation, and the received signal was processed by 32 custom IC preamplifiers that were mounted to the array connector. The amplifiers had a high input impedance compared to that of the array elements and their output impedance matched that of the coaxial cable that connected to the scanner. Because the copolymer transducer had a broad bandwidth, the spectrum of the pulse echo image was modified by the frequency dependent attenuation of tissue and the bandpass of the ultrasound scanner, resulting in a center frequency of 2.5 MHz. The performance of the copolymer array was compared to that of a 3 MHz, PZT array with similar dimensions. On the Duke phased-array scanner, the copolymer sensitivity was 28 dB less than that of PZT. The copolymer elements had a 6 dB pulse-echo angular response of 30 degrees, and the interelement cross-coupling was -35 dB. Phased-array images were made of the heart of a 25 year-old normal male. PMID- 1448891 TI - Optimum nonlinear signal detection and estimation in the presence of ultrasonic speckle. AB - A unified approach to the design of nonlinear filters for speckle suppression in ultrasound B-mode images is presented. The detection of the (lesion) signal is formulated as a binary hypothesis-testing problem. The structure of the optimal decision rules is derived both in the case where the lesion signal is assumed either a constant or random variable. In the case of a constant signal, the maximum likelihood (ML) estimator and the optimal L-estimator are derived. In the case of a random lesion signal, the maximum a posteriori probability estimator of the lesion signal has also been found. Experimental results verify the superiority of the proposed ML-estimator and the L-estimator over the straightforward choice of an arithmetic mean for speckle filtering in simulated tissue mimicking phantom ultrasound B-mode images. PMID- 1448892 TI - Large-transducer measurements of wavefront distortion in the female breast. AB - Ultrasonic waves propagating through soft tissue experience wavefront distortion. Refraction occurs at boundaries between tissue beds having different sound speeds; scattering occurs within a tissue bed, caused by local impedance variations. This paper describes measurements of wavefront distortion in the human female breast that indicate that refraction is the dominant distortion mechanism when the ultrasonic phased array is very large. The determination that refraction dominates the wavefront distortion is based upon studies of multiple image artifacts that result from a single source radiated through in vivo breasts and breast phantoms. The receiving apertures used were 4.65 and 9.6 cm. Such image artifacts are repeatedly observed in the 10 young subjects reported in this paper, and also in older subjects. An understanding of the in vivo observations is obtained by phantom studies. PMID- 1448893 TI - Adaptive imaging in aberrating media: a broadband algorithm. AB - An adaptive algorithm is derived for imaging in an aberrating medium based on wideband (time-domain) linear array data. Image reconstructions using simulated scattering data are presented. An analogy is also drawn between broadband array imaging and limited-angle tomography. This analogy suggests some tomographic-like filtering schemes that can be applied to improve the quality of the image. The algorithm is designed for imaging in composite material, although the imaging of other heterogeneous media such as tissue may be feasible under certain conditions. PMID- 1448894 TI - Role of Helicobacter felis in chronic canine gastritis. AB - Five gnotobiotic Beagle dogs were orally inoculated with a pure culture of Helicobacter felis. The remaining two littermates served as contact controls. Thirty days after infection, all animals were euthanatized and specimens were collected for evaluation. In infected dogs, H. felis was recovered from all areas of the stomach. Colonization was heaviest in the fundus and antrum. H. felis was not cultured from any segment of the gastrointestinal tract distal to the duodenum. Two weeks after infection, all five infected dogs had detectable IgM and IgG serum antibody to H. felis, whereas control dogs had no measurable H. felis serum antibody throughout the study. Histopathologic changes in the stomachs of infected dogs included large numbers of lymphoid nodules throughout all regions of the gastric mucosa and were most numerous in the fundus and body. A mild, diffuse lymphocytic infiltrate with small numbers of plasma cells and eosinophils was also present in the subglandular region of all portions of the gastric mucosa. Electron microscopic examination revealed large numbers of spiral shaped H. felis in gastric mucus adjacent to or superimposed over the areas of inflammation. Occasionally, however, H. felis was observed within the canaliculi of gastric parietal cells. Histopathologic changes in the stomachs of the contact control dogs were limited to focal infiltrates of eosinophils and small aggregates of lymphocytes in the subglandular portions of the gastric mucosa in one animal. Infection with H. felis is a likely cause of naturally occurring lymphofollicular gastritis. PMID- 1448895 TI - Rift Valley fever virus-induced encephalomyelitis and hepatitis in calves. AB - Three calves (Nos. 1, 2 = 7 days old; No. 3 = 21 days old) were inoculated subcutaneously with virulent Rift Valley fever (RVF) virus. All calves became viremic and clinically ill, but the two 7-day-old calves were moribund and were euthanatized subsequently on post-inoculation day (PID) 3. Highest viral titers were measured in the serum, with lesser concentrations in the brain, heart, spleen, and liver of these animals. Viral antigens were detected by immunohistochemical analysis only in the livers, where positive staining was localized in coalescing foci of hepatocellular necrosis. The 21-day-old calf appeared to recover after viremia and pyrexia but became lethargic and ataxic and was euthanatized on PID 9. The calf was no longer viremic, and RVF virus was isolated only from the brain. Microscopic examination of the central nervous system revealed diffuse perivascular infiltrates of lymphocytes and macrophages, multifocal meningitis, and focal areas of neuronal necrosis and aggregates of macrophages, lymphocytes, and neutrophils throughout all regions of the brain and cervical spinal cord. There was positive immunohistochemical staining for viral antigens within the cytoplasm of neurons and glial cells throughout the central nervous system. Thus, RVF virus can cause encephalomyelitis in calves, and the specific virologic diagnosis can be made by immunohistochemical localization of viral antigens in formalin-fixed tissues. PMID- 1448896 TI - Flow cytometric analysis of feline reticulocytes. AB - Hemolytic anemia was induced in five Domestic Shorthair cats (four adult males and one spayed female obtained from a breeding colony at Colorado State University, CO), and blood samples were analyzed from five other cats (two castrated male Domestic Shorthairs, one castrated male Domestic Longhair, one castrated male Persian, and one spayed female Siamese presented to the Veterinary Teaching Hospital at Colorado State University for miscellaneous problems). Blood samples taken from these cats had percentages of aggregate reticulocytes that ranged from 0% to 14.5% as determined by manual counting and were used to identify the best technique for staining cat reticulocytes for flow cytometric analysis. The best technique was mixing a blood sample (1/2,000 dilution) with 0.2 micrograms thiazole orange in 1 ml of diluent and incubating the mixture in the dark at room temperature for 30 to 60 minutes. The percentage of reticulocytes determined by flow cytometry correlated well (r = 0.88) with manually determined aggregate reticulocyte percentages; no significant differences were observed between the two techniques (P > 0.05). For the conditions used, punctate reticulocytes were not detected by flow cytometry. Samples with very high platelet numbers and very low packed cell volumes may show falsely elevated percentages of reticulocytes as determined by flow cytometry. The reproducibility of the flow cytometric technique was good; the coefficient of variation ranged from 4.8% to 17.9% in two samples with two different times of incubation. Staining of cat aggregate reticulocytes with thiazole orange and use of flow cytometric quantification is a reproducible technique that has a good correlation with the manual reticulocyte counting method. PMID- 1448897 TI - Experimental oral administration of canine adenovirus (type 2) to raccoons (Procyon lotor). AB - Canine adenovirus type 2 (CAV2) has been proposed for recombinant vaccines to control rabies in wild animals. To evaluate the suitability of CAV2 as a safe vector for the genetically engineered vaccines, seven wild-caught raccoons (three males and four females) were administered CAV2 per os. Two of the animals were euthanatized on each of post-infection days 3, 6, and 14, and one was euthanatized on day 21. Two other control raccoons (a male and a female) were also euthanatized on day 21. Microscopic pulmonary lesions of multifocal necrotizing bronchiolitis with basophilic intranuclear inclusions were seen in 3/4 raccoons euthanatized on post-infection days 3 and 6. Ultrastructural examination of lungs with pulmonary lesions revealed hexagonal viral particles characteristic of adenoviruses. CAV2 is potentially pathogenic for raccoons, and this susceptibility should be of concern to developers of recombinant vaccines who intend to use CAV2 as a vaccine vector. PMID- 1448898 TI - Immunohistochemical localization of matrix proteins in the femoral joint cartilage of growing commercial pigs. AB - The immunocytochemical localization of several matrix macromolecules, including collagen type II and proteoglycans, in the distal femoral articular-epiphyseal cartilage complex of 15 commercial pigs between the age of 6 and 18 weeks was studied. Early osteochondrotic lesions, i.e., chondronecrosis in the resting region of the growth cartilage, as well as extensions of necrotic cartilage into the subchondral bone, were present in all animals, except those 6 weeks old. A battery of antibodies were used for identification of macromolecules in the matrix at different stages of the disease. Chondrocyte involvement in the process could be studied by identifying the sequence of alterations in matrix macromolecules as the lesion developed. The immunostaining for aggrecan (large aggregating proteoglycans), cartilage oligomeric matrix protein, fibronectin, collagen type II, fibromodulin, and biglycan was more prominent in the areas of chondronecrosis, extending into the subchondral bone, than in the normal resting region. This altered pattern of matrix macromolecules resembled that of the matrix of the proliferative chondrocytes and suggests that the chondrocyte maturation had stopped in the proliferative zone. The matrix in the areas of chondronecrosis in the resting region resembled that in the normal resting region. Thus the chondronecrosis appears to have preceded alterations of the matrix composition. The antibody reactivity pattern was, however, altered in the matrix of the clustered chondrocytes in areas of chondronecrosis. Staining in these regions suggested a more prominent appearance of fibronectin and collagen type II than in the normal matrix of the resting region. These changes are suggestive of attempt to repair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448899 TI - Early sequential ultrastructural renal alterations induced by 2-bromoethylamine hydrobromide in the Swiss ICR mouse. AB - Thirty-two male Swiss ICR mice were injected intraperitoneally with 300 mg 2 bromoethylamine hydrobromide/kg body weight, anesthetized, and perfused with glutaraldehyde-paraformaldehyde solution at 5, 15, 30, 60, 90, 120, 150, and 180 minutes after treatment. Eight control mice were injected intraperitoneally with sterile diluent, and one was perfused at each of the same time periods as the treated mice. Proximal tubule epithelial alterations progressed over time from increased secondary lysosome and myeloid body formation to cellular and mitochondrial swelling and eventually cell necrosis. The glomerular, peritubular, and vasa recta capillaries had endothelial cell swelling and desquamation and platelet aggregation. Bromoethylamine nephrotoxicosis in the male Swiss ICR mouse is an ischemic necrosis of the proximal tubules and papilla initiated by endothelial cell damage and makes an excellent model of chemically induced damage to endothelial cells and tubular necrosis. PMID- 1448900 TI - Hepatic lesions in rabbits infected with Encephalitozoon cuniculi administered per rectum. AB - Microsporidia have been recognized recently as opportunistic pathogens in acquired immunodeficiency syndrome patients. In an attempt to develop an animal model of enteric microsporidiosis, adult (5 to 6 months old) male Flemish Giant rabbits from a closed New York colony were administered 5 x 10(3), 5 x 10(5), and 5 x 10(7) Encephalitozoon cuniculi per rectum. Rabbits given 5 x 10(5) and 5 x 10(7) E. cuniculi had moderate granulomatous periportal infiltrates, characterized by the presence of numerous macrophages, epithelioid cells and a few multinucleated giant cells, lymphocytes, and plasma cells. Inflammatory cells also were seen infiltrating the tunica adventitia and tunica media of hepatic portal veins and branches of the hepatic artery. This study demonstrates that administration of E. cuniculi per rectum to rabbits results in infection that is characterized by high frequency and severity of hepatic lesions. PMID- 1448901 TI - Squamous cell carcinoma arising in two feline thymomas. PMID- 1448902 TI - Testicular epidermoid cyst and penile squamous cell carcinoma in a dog. PMID- 1448903 TI - Predominance of BoCD8-positive T lymphocytes in vascular lesions in a 1-year-old cow with concurrent malignant catarrhal fever and bovine viral diarrhea virus infection. PMID- 1448904 TI - Functional thyroid follicular adenocarcinoma in a captive mountain lion (Felis concolor). PMID- 1448905 TI - Electron microscopic evidence for endothelial infection by African horsesickness virus. PMID- 1448906 TI - Chronic proliferative rhinitis associated with Salmonella arizonae in sheep. PMID- 1448907 TI - Histopathologic findings of Schistosoma margrebowiei in experimentally infected laboratory animals. PMID- 1448908 TI - Dyschondroplasia (osteochondrosis) in articular-epiphyseal cartilage complexes of three calves from 24 to 103 days of age. PMID- 1448909 TI - Dual systemic mycosis caused by Bipolaris spicifera and Torulopsis glabrata in a dog. PMID- 1448910 TI - Astrocytoma in a cynomolgus monkey (Macaca fascicularis). PMID- 1448911 TI - Identification of a binding protein to the X gene promoter region of hepatitis B virus. AB - The X protein of hepatitis B virus (HBV) is a transactivator to homologous and heterologous viral and cellular transcriptional regulatory elements. One sequence specific binding protein, whose binding site located from nt 1102 to nt 1117 of HBV DNA, was identified by mobility shift assay and DNase I foot-printing analysis. A CAT assay experiment demonstrated this 16-bp binding site to have a promoter activity in the X gene transcription. The 58-bp DNA fragment (nt 1085 to nt 1142), which contains the above binding site, could be enhanced by the HBV enhancer. Mobility shift assay using the mutated 58-bp DNA fragments as probes, showed that the mutation, which damaged the palindrome structure between nt 1105 and nt 1112, resulted in loss of the binding activity. This mutation also remarkably reduced the promoter activity. The binding site differed from the target sequences of known transcriptional factors. This factor was thus concluded to be a binding protein to the X gene promoter (X-PBP) of HBV. A homology search demonstrated the binding site to be highly homologous to the promoter elements of human laminin receptor (2H5epitope) and lipoprotein receptor-related protein (LRP) genes. PMID- 1448912 TI - Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses. AB - Mutations in the influenza M2 membrane protein which confer resistance to the antiviral drug amantadine are exclusively located within the transmembrane region of the molecule. The influence of specific amino acid substitutions on the activity of the M2 protein in influenza A virus-infected cells is assessed in this report by their effects upon haemagglutinin (HA) stability and virus growth. A number of amino acid substitutions, e.g., L26H, A30T, S31N and G34E reduced the activity of the M2 protein of A/chicken/Germany/34 (Rostock) and caused a substantial increase in expression of the low-pH form of HA. The adverse effects of the mutations on virus replication were evident from changes selected during subsequent passage of the mutant viruses in the presence or absence of amantadine: reversion to wt, the acquisition of a second suppressor mutation in M2, or the appearance of a complementary mutation in HA which increased its pH stability. In contrast, 127T and 127S, mutations which were most readily selected following passage of the wt virus in the presence of drug, caused an increase in M2 activity. Furthermore, in double mutants the 127T mutation suppressed the attenuating effects of the A30T and S31N mutations on M2 activity. The influence of primary structure on the consequences of particular amino acid changes was further emphasized by the contrasting effects of the G34E mutation on the activities of two closely related proteins, causing an increase in the activity of the M2 of A/chicken/Germany/27 (Weybridge) as opposed to the decrease in activity of the Rostock protein. Estimates of differences in trans Golgi pH based on the degree of conversion of HA to the low-pH form, or complementation of differences in pH stability of mutant HAs, indicate that changes in M2 may influence pH within the transport pathway by as much as 0.6. The results thus provide further evidence that M2 regulates transmembrane pH gradients in the trans Golgi. Incompatibility between particular HA and M2 components and the selection of M2 mutants with suboptimal activity stresses the essential relationship between the structures and functions of these two virus proteins. PMID- 1448913 TI - Molecular cloning and sequencing of the Mexico isolate of hepatitis E virus (HEV). AB - Hepatitis E virus (HEV) is the major causative agent of hepatitis E or what was formerly known as enterically transmitted non-A, non-B hepatitis. The disease has a worldwide distribution but occurs principally in developing countries in any of three forms: large epidemics, smaller outbreaks, or sporadic infections. Genetic variation of different HEV strains was previously noted and it will be important to determine the extent to which this variation may pose problems in the diagnosis and treatment of HEV infection. To analyze differences at the genetic level between HEV(Mexico; M) and the previously characterized HEV(Burma; B) and HEV(Pakistan; P) isolates, overlapping cDNAs were cloned from samples obtained from an infected human and an experimentally inoculated cynomolgus macaque. These cDNA clones, representing the nearly complete (7185-bp) genome of HEV(M), confirmed an expression strategy for the virus that involves the use of 3 forward open reading frames (ORFs). The HEV(M) strain has an overall 76 and 77% nucleic acid identity with the HEV(B) strain and HEV(P) strain, respectively; however, the degree of sequence variation was not uniform throughout the viral genome. A hypervariable region was identified in ORF1 that exhibited a 58 and 54% nucleic acid sequence and 13% amino acid similarity with the Burma strain and the Pakistan strain, respectively. A large number of the nucleotide differences occurred at the third codon position, with the deduced amino acid sequences similarity of 83, 93, and 87% between HEV(M) and HEV(B) isolates in ORF1, ORF2, and ORF3, respectively, and with 84, 93, and 87% amino acid identities between HEV(M) and HEV(P) isolates in ORF1, ORF2, and ORF3, respectively. The nucleotide sequences derived from the highly conserved regions of HEV genome will be useful in developing polymerase chain reaction-based tests to confirm the viral infection. Knowledge of the extent of the sequence variation encountered with HEV will not only aid in the future development of diagnostic and vaccine reagents but also further our understanding of how HEV strain variation might impact the pathological outcome of infection. PMID- 1448914 TI - Two strains of SIVmac show differential transactivation mediated by sequences in the promoter. AB - Two infectious molecular clones of simian immunodeficiency virus, SIVmac251 and SIVmac239, have very different in vivo properties, SIVmac239 being much more pathogenic than SIVmac251. To assess whether the in vivo differences between the two viruses would be reflected in transcriptional rates in vitro, transcriptional activity in the presence of the transactivation protein tat was analyzed by transient transfection assays in HUT-78 and U937 cells. Whereas the two promoters had similar basal activities (Anderson and Clements, 1991, J. Virol. 65, 51-60) the promoter of SIVmac239 was transactivated to a greater extent. Removal of sequences 5' to -225 and 3' to +18 maintained the basal activity, yet made the promoter unresponsive to tat. Addition of bases +19 to +149 reconstituted transactivation and decreased basal activity. Analysis of deletion mutants with reconstituted transactivation response region determined that differences between the two strains were maintained even when only the proximal sequences, -225 to +18 of the U3 and R region were placed upstream of the TAR sequences. This region contains four nucleotide differences and the potential Sp-1-binding sites, where there are an additional 11 bases in SIVmac239 that create a third potential Sp-1 site, compared to only 2 in SIVmac251. Transactivation in this assay system was found to correlate better to RNA differences shortly after transfection (12 hr) than later (46 hr). PMID- 1448915 TI - Genetic evidence that epizootic Venezuelan equine encephalitis (VEE) viruses may have evolved from enzootic VEE subtype I-D virus. AB - An important question pertaining to the natural history of Venezuelan equine encephalitis (VEE) virus concerns the source of epizootic, equine-virulent strains. An endemic source of epizootic virus has not been identified, despite intensive surveillance. One of the theories of epizootic strain origin is that epizootic VEE viruses evolve from enzootic strains. Likely enzootic sources of VEE virus occur in Colombia and Venezuela where many of the epizootic outbreaks of VEE have occurred. We have determined the nucleotide sequences of the entire genomes of epizootic VEE subtype I-C virus, strain P676, isolated in Venezuela, and of enzootic VEE subtype I-D virus, strain 3880, isolated in Panama. VEE subtype I-D viruses are maintained in enzootic foci in Panama, Colombia, and Venezuela. The genomes of P676 and 3880 viruses differ from that of VEE subtype I AB virus, strain Trinidad donkey (TRD), by 417 (3.6%) and 619 (5.4%) nucleotides, respectively. The translated regions of P676 and 3880 genomes differ from those of TRD virus by 54 (1.4%) and 66 (1.8%) amino acids, respectively. This study and the oligonucleotide fingerprint analyses of South American I-C and I-D viruses (Rico-Hesse, Roehrig, Trent, and Dickerman, 1988, Am. J. Trop. Med. Hyg. 38, 187 194) provide the most conclusive evidence to date suggesting that equine-virulent strains of VEE virus arise naturally from minor variants present in populations of I-D VEE virus maintained in enzootic foci in northern South America. PMID- 1448916 TI - Characterization of TH3, an induction-specific protein interacting with the interferon beta promoter. AB - We report the purification and characterization of a unique DNA-binding protein termed TH3 that interacts with the positive regulatory domain (PRD) I and PRDIII domains of the interferon (IFN) beta promoter. In cells treated with poly rl:rC and cycloheximide, appearance of TH3 DNA-binding activity was inversely proportional to the disappearance of a constitutive complex TH1 and coincided temporally with induction of IFN-beta gene transcription. The TH3 DNA-binding protein is a small 14-kDa polypeptide that appears to be derived from the TH1 complex; TH1 in turn is related to interferon regulatory factor (IRF) 2 by immunological cross-reactivity. The TH3 protein appeared to lack the epitope required for recognition by anti-IRF-2 antisera; however, a short microsequence obtained for TH3 overlapped a sequence from the IRF-2 protein. Although TH3 binds to multimers of the AAGTGA hexamer and to PRDI, the TH3 protein alone had a predominantly neutral phenotype on PRDI-dependent transcription in vitro and lacked the negative transcriptional effect attributed to IRF-2. These results raise the possibility that specific proteolysis of a negative regulatory protein involved in silencing the IFN-beta promoter may be an important event leading to transcriptional activation of the interferon gene. PMID- 1448917 TI - Cloned DNA copies of cowpea severe mosaic virus genomic RNAs: infectious transcripts and complete nucleotide sequence of RNA 1. AB - Cowpea severe mosaic virus (CPSMV) is a member of the comovirus group of messenger-sense RNA viruses with bipartite genomes, of which cowpea mosaic virus (CPMV) is the type member. Full-length copies of CPSMV RNA 1 were cloned in plasmids bearing a bacteriophage T7 promoter. Previously, similar clones of CPSMV RNA 2 had been obtained. A 5'-rUAUUAAAAUUUU sequence is common to RNA 1 and RNA 2. From two RNA 1 clones and four RNA 2 clones we excised non-CPSMV sequences so as to provide templates for in vitro transcripts that have only a single guanylate preceding CPSMV RNA sequences. Transcripts from the most active RNA 1 and RNA 2 clones, when mixed, showed about 5% of the infectivity of unfractionated CPSMV RNAs from virions. The longest, 1858 codon open reading frame of the 5957 nt CPSMV RNA 1 extends from an AUG at nt 257 to a UGA termination codon at nt 5831. The calculated molecular weight of the polyprotein is 208,000. Comparisons with the available amino acid residue (aa) sequence information from the complete CPMV RNA 1 sequence and the partial sequence of red clover mottle virus RNA 1 suggest that CPSMV RNA 1 specifies the expected set of five mature proteins: 32K proteinase cofactor, 58K presumed helicase, VPg 5' linked protein of the genomic RNAs, 24K proteinase, and 87K presumed polymerase, separated by four cleavage sites. Of the determined and deduced cleavage sites of the three RNA 1 polyproteins, only that at the 24K/87K junction has a distinct aa pair in the CPSMV polyprotein. Of the five proteins, VPg and 87K show the greatest similarity between CPSMV and CPMV, with identities of 68 and 55%, respectively. Published mutational analysis of the CPMV 24K proteinase and alignment of aa sequences from three comoviruses suggest that cysteine-168, histidine-40 and glutamic acid-77 form the catalytic triad of the CPSMV 24K proteinase. Results are discussed in the context of the resistance that some cowpea (Vigna unguiculata) lines exhibit against CPMV but not against CPSMV. PMID- 1448918 TI - In situ immunogold labeling analysis of the rice hoja blanca virus nucleoprotein and major noncapsid protein. AB - Ribonucleoprotein particles (RNPs) of rice hoja blanca virus (RHBV) were purified and used for electron microscopic analysis and antibody production. Antibodies made to RNPs specifically decorated purified RNPs. The RNPs typically showed characteristic tenuivirus morphologies. They were approximately 8 nm in diameter, mostly circular in nature, and exhibited branching and a high degree of superhelicity. When the RNP antibodies were used for in situ immunogold labeling analysis of RHBV-infected tissues, no specific structures were identified, but gold particles were distributed throughout the cytosol of RHBV-infected but not healthy plants. However, amorphous semi-electron opaque inclusion bodies (ASO IBs) were abundant in cells of RHBV-infected plants. While the ASO-IBs were not labeled with the anti-RNP antiserum, they were specifically labeled with antibodies to the RHBV major noncapsid protein (NCP) and with antibodies to the NCP of another tenuivirus, maize stripe virus. PMID- 1448919 TI - Regulation of the efficiency and thermodependence of murine sarcoma virus MuSVts110 RNA splicing by sequences in both exons. AB - Efficient splicing of MuSVts110 RNA is restricted to temperatures of 33 degrees or lower. Previously, we have shown that this conditional splicing event is mediated, in part, by cis-acting intronic sequences. We have now examined the role of exon sequences in MuSVts110 RNA splicing. We found that deletion of all but 36 nucleotides of the gag exon (E1) yielded a transcript incapable of supporting splicing. However, inefficient, growth temperature-dependent splicing was recovered after restoration of the 300 nucleotides of E1 proximal to the 5' splice site (5' ss). Increasingly efficient splicing was observed as more E1 was restored. Hence, although MuSVts110 E1 sequences were required for splicing, they were not involved in its thermodependence. Similarly, removal of all but 88 nucleotides of the mos exon (E2) abolished splicing at the usual 3' splice site (3' ss). In contrast to E1, restoration of the 200 nucleotides of E2 adjacent to the 3' ss reactivated efficient, temperature-independent splicing. Thermodependent splicing, however, reappeared with the replacement of E2 sequences located more than 400 nucleotides distal to the 3' splice site. In MuSVts110 mutants containing the minimum amounts of both E1 and E2 which would support splicing, splicing was both far more efficient than predicted and temperature-independent, suggesting that cooperation between E1 and E2 may help to regulate MuSVts110 splicing. PMID- 1448920 TI - Analysis of proviruses integrated in Fli-1 and Evi-1 regions in Cas-Br-E MuLV induced non-T-, non-B-cell leukemias. AB - The DNAs of the Cas-Br-E MuLV-induced leukemias always contain somatically acquired mink cell focus-forming (MCF) recombinant proviruses. MCF recombinants could be involved during leukemogenesis at both preleukemic times and in late stage tumors. Among the Cas-Br-E-induced non-T-, non-B-cell leukemias, viral integrations were found in the Fli-1 and Evi-1 region in 71% (36 out of 51) and 22% (16 out of 72) of the tumors analyzed, respectively. As an approach to evaluate the contribution of Cas-Br-E MCF recombinant formation in cis-activation of proto-oncogenes, we analyzed the structure of the Fli-1- and Evi-1-associated proviruses by Southern blot hybridization. In Fli-1, we found that the proviruses, ecotropic as well as MCF, are all integrated within a very short DNA region immediately upstream of the initiator ATG, toward the 3' end of a 5' exon (Ben-David, Giddens, Letwin, and Bernstein, 1991, Genes Dev. 5, 908-918). All proviruses are oriented the same way, in the 5' to 3' transcriptional sense. Both provirus types are able to direct the Fli-1 expression to the same extent presumably via a promoter insertion mechanism. Most of the proviruses had no detectable deletion and contained both 5' and 3' LTR sequences with similar U3 sequences. MCF recombinants did not show any selective advantage over ecotropic proviruses for the Fli-1 locus since the frequency of ecotropic to MCF recombinant virus at the Fli-1 locus was identical to that observed at any other locus. This suggests that the formation of these MCF recombinants is not essential for activation of Fli-1 and that ecotropic Cas-Br-E already possesses the required sequences for full cis-activation of Fli-1. On the other hand, in Evi-1, there is a strict selection for ecotropic proviruses. Presumably, viral genetic elements outside of the U3 region could be critical for the Evi-1 cis activation. PMID- 1448921 TI - Interaction of cellular factors with intragenic cis-acting repressive sequences within the HIV genome. AB - Expression of the human immunodeficiency virus (HIV) structural gene products is suppressed in the absence of the Rev protein. The block to expression reflects, in part, nuclear retention of those mRNAs which encode the structural proteins. The presence of intragenic cis-acting repressive sequences (CRS) and inefficient splicing of the primary viral transcript are thought to contribute to nuclear entrapment of viral RNA. To elucidate the mechanism for repression of HIV gene expression, the ability of a 270-bp segment of the pol gene shown previously to repress gene expression to interact with cellular factors was investigated. Incubation of RNA corresponding to the 270-bp CRS element with nuclear extract prepared from human T-cells revealed a strong and specific interaction with several cellular factors. Covalent cross-linking of the RNA-protein complex demonstrated the presence of at least three proteins, the predominant one having a molecular weight of approximately 42 kDa. A monoclonal antibody raised against hnRNP C, a component of the splicing machinery, recognized the CRS-protein complex, suggesting that hnRNP C or a closely related gene product interacts with CRS-containing RNA. Consistent with this conclusion, addition of RNA corresponding to a beta-globin intron sequence in the binding reaction completely blocked formation of the CRS-protein complex. These findings raise the possibility that the CRS elements elicit nuclear entrapment of viral RNA through formation of RNA-protein complexes that are not accessible to nuclear export pathways. PMID- 1448922 TI - The E3-11.6K protein of adenovirus is an Asn-glycosylated integral membrane protein that localizes to the nuclear membrane. AB - The 11,600 MW (101 amino acids; 11.6K) protein of adenovirus 2 (Ad2) is a protein of unknown function which is synthesized in low amounts during early stages of infection but in very high amounts at late stages. The 11.6K protein migrates as three major groupings of diffuse bands of ca. 14K, 21K, and 31K on SDS-PAGE, indicating that 11.6K undergoes post-translational modification. We show here that 11.6K is Asn-glycosylated with complex (endo H-resistant) oligosaccharides and that 11.6K is an integral membrane protein. Immunofluorescence indicated that 11.6K initially is associated with the endoplasmic reticulum and Golgi apparatus and that it ultimately localizes to the nuclear membrane. The 11.6K protein is predicted to have a single signal-anchor sequence at residues 41-62 and only one potential Asn-linked glycosylation site at residue 14; thus, 11.6K must be oriented in the membranes with its NH2-terminus in the lumen and its COOH terminus in the cytoplasm. The signal-anchor and glycosylation features of 11.6K are preserved in Ad2 and Ad5 (group C), and in Ad3 and Ad7 (group B), but the sequence of 11.6K is more diverged among these serotypes than is the sequence of most other adenovirus proteins. PMID- 1448923 TI - Adenovirus type 12 early region 1B proteins and metabolism of early viral mRNAs. AB - Early region 1B (E1B) of human adenoviruses encodes two major proteins. The 19 kDa polypeptide appears to prevent E1A-induced cytolysis and DNA degradation. The larger E1B product of approximately 55 kDa, which is essential for viral replication, plays a role in the accumulation and stability of viral mRNAs and the late shutoff of host metabolism. For serotype 12 (Ad12), this 482-residue (482R) protein is essential for viral DNA replication. In the present report we have used a series of mutants to examine the roles of Ad12 482R and the 19-kDa, 163R protein in the metabolism of early viral mRNAs. No specific effects on the accumulation of early (or late) mRNAs were detected with any of the mutants affecting 163R. With mutant dl42, which encodes an altered 482R product that lacks residues 114-155, both viral DNA replication and late viral protein synthesis were defective. Accumulation of E1A transcripts in the nucleus and cytoplasm resembled wt. The levels of mRNAs from early regions E1B, E2A and E3 at later times during infection were somewhat lower than those of wt, but this decrease may have been due to the absence of progeny viral DNA in dl42-infected cells. However, the accumulation of both E2B and E4 mRNAs at all times was severely reduced. These data suggested that the requirement of 482R for Ad12 DNA replication may be related to its specific role in the metabolism of E2B and E4 mRNAs that encode products necessary for viral DNA synthesis. PMID- 1448924 TI - Vaccinia virus gene B1R encodes a 34-kDa serine/threonine protein kinase that localizes in cytoplasmic factories and is packaged into virions. AB - Vaccinia virus open reading frame B1R was expressed in E. coli and shown to encode a serine/threonine protein kinase which phosphorylated casein and calf thymus histones in vitro. A polyclonal rabbit antiserum was raised against a TrpE B1R bacterial fusion protein and used to characterize the B1R gene product. Immunoprecipitation and immunoblotting analyses detected a 34-kDa polypeptide that was synthesized early during vaccinia virus infection and which was apparently stable since it was easily detectable 18 hr postinfection. Immunofluorescence demonstrated that this protein localizes in cytoplasmic virus factories, the sites of virus DNA replication. Immunoblotting of vaccinia virions showed that the enzyme is packaged into virus particles. PMID- 1448925 TI - The restricted nature of HIV-1 tropism for cultured neural cells. AB - Infection of the central nervous system by HIV-1, the agent of AIDS, is characterized by the presence of infected and giant microglial cells as well as astrocytosis, demyelination, and neuronal loss. To determine whether cells of neuroectoderm origin can be infected by HIV-1, we have inoculated primary cultures derived from adult human brain with a lymphotropic virus (LAV) or a neurotropic virus (Jr-FL) isolated from a patient with AIDS dementia. While Jr-FL invariably causes productive infection of cultured brain microglia, neither astrocytes nor oligodendrocytes became productively infected by these viral strains. Moreover, the cultured oligodendrocytes develop a normal network of processes and express differentiation antigens in the presence of an ongoing lytic infection of microglial cells. No HIV-1 proviral DNA was detected in primary astrocyte cultures devoid of microglial after inoculation of either HIV-1 strain. Similarly, the neuronal cell line HCN-1 in its differentiated state did not allow the virus to go through cycles of reverse transcription and replication. LAV, however, was able to replicate in undifferentiated HCN-1 cells. Thus, tropism of HIV-1 appears tightly restricted to only one type of differentiated cell in the CNS, the microglia. PMID- 1448926 TI - Expression and secretion of Japanese encephalitis virus nonstructural protein NS1 by insect cells using a recombinant baculovirus. AB - The nonstructural protein NS1 of Japanese encephalitis virus (JEV) was expressed at a high level under the control of the polyhedrin promoter in Spodoptera frugiperda (Sf9) insect cells using a recombinant baculovirus. Recombinant NS1 was designed to contain its natural signal sequence at its N-terminus and no C terminal hydrophobic domain that could act as a membrane anchor. This recombinant protein exhibited similar size to native NS1 expressed in Aedes albopictus (C6/36) insect cells infected with wild-type JEV. The signal sequence of NS1 allowed translocation of the protein into the endoplasmic reticulum where it underwent glycosylation. A small fraction of synthesized NS1 was able, in the absence of any other viral protein, to associate as a homodimer, showing similar characteristics to the native dimer. Interestingly, this recombinant dimeric form seemed to be exported and released in the extracellular medium of infected cell culture. During its transport, one of the two N-linked oligosaccharides of the polymannose type was processed to an endoglycosidase H-resistant form, suggesting that the protein had passed through the Golgi compartment before reaching the cell surface. Moreover, Triton X-114 partitioning analysis showed that monomeric NS1 behaved essentially as a hydrophilic protein, whereas both intracellular and extracellular dimeric NS1 were either free of or associated to membraneous components. PMID- 1448927 TI - Complex intrapatient sequence variation in the V1 and V2 hypervariable regions of the HIV-1 gp 120 envelope sequence. AB - Human immunodeficiency virus (HIV) quasi-species fluctuate both in time and in space. In general intrapatient variation is less extensive than interpatient variation. The V1 and V2 hypervariable regions of the envelope gene were analyzed for patient samples harboring highly divergent genomes in other loci. Proviral sequences were amplified by PCR, cloned, and sequenced. It was concluded that intrapatient variation may exceed interpatient variation but the presence of two clearly distinct populations was not confirmed. The env hypervariable regions appeared to be evolving independently of one another, cautioning against extrapolation of data, particularly from the V3 region. Virus typing and the assessment of HIV superinfection by genetic methods will prove difficult and experimental approaches will have to be carefully designed. PMID- 1448928 TI - The trypsin-sensitive RVER domain in the capsid proteins of minute virus of mice is required for efficient cell binding and viral infection but not for proteolytic processing in vivo. AB - Analysis of a series of mutations in the trypsin-sensitive RVER region of the amino terminal domain in the capsid proteins (VP1 and VP2) of the autonomous parvovirus, minute virus of mice (MVM), demonstrates that this sequence is not essential for proteolytic processing of VP2 into VP3 in vivo, but specific amino acids within this domain are important for viral infection. Analysis of the most deficient of these mutants, VP(delta 2842-2863), a 7-aa deletion of aa 159-165 in VP1 and 17-23 in VP2, has identified at least two steps in MVM infection in which this domain is important. VP(delta 2842-2863) was 3-fold defective in binding to murine A9(2L) cells and, when an equivalent amount of virus was bound to cells, additionally 10-fold deficient compared to wild-type in initiating a productive infection. However, in those cells effectively infected, VP(delta 2843-2863) replicated similar to wild-type. These results suggest that these seven amino acids constitute a region important for both binding and a subsequent step prior to the start of DNA replication such as viral uptake or transport to the nucleus. PMID- 1448929 TI - Identification of the active site residues in the nsP2 proteinase of Sindbis virus. AB - The nonstructural polyproteins of Sindbis virus are processed by a virus-encoded proteinase which is located in the C-terminal domain of nsP2. Here we have performed a mutagenic analysis to identify the active site residues of this proteinase. Substitution of other amino acids for either Cys-481 or His-558 completely abolished proteolytic processing of Sindbis virus polyproteins in vitro. Substitutions within this domain for a second cysteine conserved among alphaviruses, for four other conserved histidines, or for a conserved serine did not affect the activity of the enzyme. These results suggest that nsP2 is a papain-like proteinase whose catalytic dyad is composed of Cys-481 and His-558. Since an asparagine residue has been implicated in the active site of papain, we changed the four conserved asparagine residues in the C-terminal half of nsP2 and found that all could be substituted without total loss of activity. Among papain like proteinases, the residue following the catalytic histidine is alanine or glycine in the plant and animal enzymes, and the presence of Trp-559 in alphaviruses is unusual. A mutant enzyme containing Ala-559 was completely inactive, implying that Trp-559 is essential for a functional proteinase. All of these mutations were introduced into a full-length clone of Sindbis virus from which infectious RNA could be transcribed in vitro, and the effects of these changes on viability were tested. In all cases it was found that mutations which abolished proteolytic activity were lethal, whether or not these mutations were in the catalytic residues, indicating that proteolysis of the nonstructural polyprotein is essential for Sindbis replication. PMID- 1448930 TI - Constitutive expression of the nef gene suppresses human immunodeficiency virus type 1 (HIV-1) replication in monocytic cell lines. AB - In order to study the effect of nef gene expression on viral replication in monocytic cells, we established monocytic (U937 and THP-1) cell transfectants constitutively expressing the human immunodeficiency virus type 1 nef gene. We constructed a plasmid expressing the nef gene derived from an infectious clone, NL432, under the control of SR alpha promoter which can drive a high level of gene expression. We found suppressed viral replication in nef-expressing monocytic cells, although a negative effect of nef was observed, with some variation depending on the virus strain and the cell. We also observed that the expression of the surface CD4 molecule is inversely related to the expression of the nef gene, especially in the U937 transfectants. These results indicate that the suppression of viral replication and the down-modulation of CD4 molecule by nef gene expression occur in monocytic cell lines as in T cell lines. PMID- 1448931 TI - Natural variants of the HIV-1 long terminal repeat: analysis of promoters with duplicated DNA regulatory motifs. AB - Sequence variation in the long terminal repeat (LTR) region of HIV-1 was analyzed in viral isolates of 17 infected individuals. Two classes of LTR size variants were found. One HIV-1 variant was detected containing an additional binding site for the transcription factor Sp1. Another LTR size variation was observed in four patients in a region just upstream of the NF-kappa B enhancer. This variation was the result of a duplication of a short DNA sequence (CTG-motif). Cell culture experiments demonstrated that the natural variant with four Sp1 sites had a slightly higher promoter activity and viral replication rate than the isogenic control LTR with three Sp1 sites. No positive effect of the duplicated CTG-motif could be detected. In order to measure small differences in virus production more accurately, equal amounts of a size variant and the wild-type plasmid were cotransfected into T-cells. The virus with four Sp1 sites did outgrow the three Sp1 virus in 35 days of culture and CTG-monomer virus outcompeted the CTG-dimer virus in 42 days. Based on these results we estimate a 5-10% difference in virus production of the LTR variants when compared to that of wild-type. PMID- 1448932 TI - Rice dwarf phytoreovirus segment S12 transcript is tricistronic in vitro. AB - Sequence analysis revealed that rice dwarf phytoreovirus segment S12 is 1066 nucleotides long with a small out-of-phase, overlapping open reading frame (ORF) as well as a major ORF. The large ORF (positions 42 to 980) encodes 312 amino acids, while the small one (bases 313 to 591) encodes 92 amino acids with an additional in-frame AUG codon (positions 337-339) 24 nucleotides downstream from the first one. Transcripts from a full-length cDNA directed the in vitro synthesis of three polypeptides of 33 (considered to be translated from the long ORF), 8, and 7 kDa. Alteration of each of the two ATG codons on the small ORF demonstrated their involvement in the generation of the 8- and 7-kDa polypeptides. Although it is still unknown whether these proteins are expressed in vivo, the small ORF is shown to be conserved in S9s of two other members of the genus Phytoreovirus, rice gall dwarf virus and wound tumor virus, suggesting its common, important function. PMID- 1448933 TI - The genetic evolution of the envelope gene of simian immunodeficiency virus in cynomolgus macaques infected with a complex virus pool. AB - Two cynomolgus macaques were infected with a complex, but characterized, challenge stock of simian immunodeficiency virus (SIVmac251 32H). The polymerase chain reaction was applied in a temporal sequence analysis to determine the sequences of the gp120 region of the SIV env gene, which were present in the blood of both macaques at 1, 6, and 15 months postinfection (p.i.). At 1 month p.i. selected sequences, which had been present in the original virus challenge stock, were reisolated. At later times, new sequences emerged, which had not been detected in the original virus challenge stock. Changes in sequence were restricted to specific regions of gp120, notably those equivalent to V1, V2, V4, and V5 of HIV-1, but not V3. The diversity and the rate of appearance of new sequences in the V1 region suggest that genetic evolution occurs by mechanisms in addition to nucleotide substitutions. These results are discussed in relation to the role of the envelope protein in the generation of protective immunity against infection with immunodeficiency viruses. PMID- 1448934 TI - [Changes in the lymphatic system in the crush syndrome]. AB - In vivo indirect electrolymphoroentgenography was conducted to study the reaction of lymphatics during prolonged compression syndrome (PCS). The studies were made on white rats, Wistar-line, males. It was found out that the early period of clinical course of PCS was characterized by lymphostasis. The intermediate period of PCS corresponds to the stage of the collateral lymphokinesis. At the edge of intermediate and late period of PCS the electrolymphoroentgenogram shows the removal of lymphostasis and recovery of main lymphokinesis. PMID- 1448935 TI - [Ultrasonic study of the thyroid in the population living in areas contaminated by radioactive substances after the accident at the Chernobyl Atomic Electric Power Station]. PMID- 1448936 TI - [The modelling of battle factors in the special tactical training of the personnel in a medical service troop unit]. PMID- 1448937 TI - [The scope of the medical care for the wounded and sick during their evacuation]. PMID- 1448938 TI - [The garrison joint medical aid station]. PMID- 1448939 TI - [The deontological aspects of the legal regulation of the activities of military medical commissions]. AB - Practically, the questions of deontology are not working out in the sphere of military medical rating (expertise). Finally this fact leads to methodical errors, defects in medical examinations, and thus to a considerable number of requests and complaints. The authors examine the basic questions of deontology from the point of view of the following aspects: collegiality, obligation to render the verdict on medical examination in the presence of examinee, medical secrecy and strict legal regulation of this norm, deontological questions in drawing up, filling in, storing and giving out medical rating documents. PMID- 1448940 TI - [The prospects for the use of a Soviet apparatus for the removal of gallstones with focused shock waves]. AB - Clinico-experimental substantiation was conducted for extracorporal crushing of the stones in biliary ducts in patients who suffered from gallstone disease. The "Urat-II" national lithotriptor and "Urat-B" biostand were used to crush in experimental conditions 140 gallstones (0.5-2.5 cm in size) obtained during cholecystectomies. Experimental researches on 56 white rats were conducted to study the liver tissue and adjacent organs. Optimal regimes for the percussive wave generator were found out in which the best crushing effect was obtained (with the dimensions of fractions up to 1.6 mm) and at the same time the minimal disturbing factor was produced. The data obtained during these researches are used in clinical pilot testings on "Urat-II"--a prototype of the national cholelithotriptor. PMID- 1448941 TI - [The classification of combined craniocerebral injuries from the use of nuclear weapons]. PMID- 1448942 TI - [Regional dehydration in the combined treatment of fractures of the bones of the extremities]. AB - The article makes a theoretical substantiation of regional dehydration in the treatment of the posttraumatic swellings in bone fractures of the extremities. The state of regional hemodynamics in 226 patients with the affections of bones and vessels of the extremities was studied using clinical, functional and angiographical methods. The authors make a conclusion concerning the efficiency of the proposed method of treatment for posttraumatic swellings of the extremities, which is based on the rapid enhancing of the mole-factor in the blood plasma in order to recover optimal conditions for the exchange process and microcirculation. This method of regional dehydration is proposed by the authors as an alternative to the fasciotomy which is based on mechanical influence upon extravasal squeezing of vessels. PMID- 1448943 TI - [The clinico-immunological aspects of a repeat myocardial infarct]. PMID- 1448944 TI - [The first results of lithotripsy performed with the LT.01 apparatus of the EDAP firm]. PMID- 1448945 TI - [The current diagnostic problems of HIV infection in military medicine]. PMID- 1448946 TI - [The medical aspects of the analysis of chemical accidents]. PMID- 1448947 TI - [The epidemiological, clinical, diagnostic and treatment aspects of Legionella infection]. AB - The article studies the modern problems of legionellosis infection and gives data concerning epidemiological aspects of this disease, especially clinical course of its types (pneumonia, acute respiratory viral infection syndrome, alveolitis, pleuritis), as well as methods of bacteriological and serological diagnostics, and etiotropic treatment. The authors use their own materials to describe the restricted outbreak of legionellosis infection and sporadic cases of this disease. The article makes clinic classification of legionellosis taking into account various publications and the proper experience of the authors. PMID- 1448948 TI - [The assessment of body functional systems by the indices of their nonspecific reactions]. AB - The analysis of long standing researches in the military operators' procedure has shown some regularities in the changes of indices which were examined. Varying in time and magnitude the non-specific reactions at first manifest itself in unstable vegetative regulations, then proliferate its influence upon visual and motor coordination, and finally cause negative shifts in professional activities (worsening of accuracy and precision, appearance of errors, etc). It is obvious, that specific reactions impose their own features on the development of this program without changing its basic trend. PMID- 1448949 TI - [Subjective reactions and the objective assessment of the hearing and ventilatory functions of the middle ear during changes in atmospheric pressure]. PMID- 1448950 TI - [The psychophysiological characteristics of the activities of flight personnel during the mastery of VTOL aircraft]. PMID- 1448951 TI - [The effect of PCL-6 photochromic lenses on the visual functions and work capacity of sailors under bright sunlight]. PMID- 1448952 TI - [Experience in organizing emergency neurosurgical care in a clinical hospital]. PMID- 1448954 TI - [The potentials of echocardiography in diseases of the cardiovascular system]. PMID- 1448953 TI - [The work of an irregular central sterilization unit in a hospital]. PMID- 1448955 TI - [The use of a multichannel radiobiotelemetric system with patients with ischemic heart disease]. PMID- 1448956 TI - [The characteristics of the course of the sequelae of nonsevere craniocerebral trauma in young people]. PMID- 1448957 TI - [The accuracy of the x-ray localization of intraocular foreign bodies]. PMID- 1448958 TI - [The organization of protection for personnel and medical care for victims in the contamination of a site by powerful poisonous substances]. PMID- 1448959 TI - [An outstanding Soviet pharmacologist (on the centenary of the birth of S. V. Anichkov)]. PMID- 1448960 TI - Variants of hepatitis B virus. PMID- 1448961 TI - Determination of total protein in highly purified factor IX concentrates. AB - Protein determination by the methods of Kjeldahl, Biuret, Bradford and UV absorbance at 280 nm have been studied in regard to accuracy, precision and simplicity. A reference preparation of a highly purified factor IX concentrate, Nanotiv, reconstituted to 1/5 of ordinary volume was used in the study in order to make a comparison between the different procedures. The Kjeldahl method resulted in a protein concentration of 3.7 mg/ml, whereas the Biuret, Bradford (BSA) and UV absorbance at 280 nm resulted in protein concentrations of 3.6, 2.5 and 2.8 mg/ml, respectively. The corresponding values for specific activity were 136, 140, 200 and 179 IU/mg, respectively. These results demonstrate a great variation in the response obtained by different methods for determination of total protein. PMID- 1448962 TI - Manufacture and in vitro characterization of a solvent/detergent-treated human plasma. AB - We have developed a modified solvent/detergent (S/D) treatment to inactivate viruses in human plasma using 1% w/w final concentration of tri(n-butyl) phosphate (TNBP) and Triton X-100 and an incubation period of 4 h at 30 degrees C. The procedure inactivates > or = 10(6) chimpanzee-infectious doses (CID50) of HBV, > or = 10(5) CID50 of HCV, and > or = 10(6.2) tissue culture infectious doses (TCID50) of HIV. After virus inactivation, eleven plasma batches were lyophilized and 12 batches were deep-frozen until further use. The batches were characterized by extensive laboratory tests including measurement of clotting factors I-XIII, von Willebrand factor, plasminogen, inhibitors of blood coagulation and fibrinolysis, and other clinically important plasma proteins. All parameters were determined before and after S/D treatment. Twelve conventional single donor plasma units served as control. There were no marked losses of activities of clotting factors, antithrombin III, protein C, plasminogen, and C1 esterase inhibitor due to treatment. After the S/D step, the levels of these parameters were within the normal range in all batches. The same holds true for total protein, immunoglobulins, albumin, complement factors C3 and C4, haptoglobin, hemopexin, caeruloplasmin, alpha 1-antitrypsin, and pH. Protein S and alpha 2-antiplasmin activities decreased by about 50% and were frequently found to be slightly below the lower limit of the respective normal range after treatment. The interindividual variations of all proteins analysed were significantly lower than in the single donor plasma units. The S/D procedure did not lead to increases of markers indicating activation of hemostasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1448963 TI - A decade of rare donor services in the United States. Report of the American Red Cross Rare Donor Registry (1981-1990). AB - Between 1981 and 1990, the American Red Cross Rare Donor Registry supplied 9,872 units of red cell components with rare phenotypes to blood centers in the United States and abroad. Approximately 51% were from donors with high-frequency antigen negative phenotypes and 49% were from donors with multiple antigen-negative phenotypes. Since 1989, the disease category requiring the largest number of units has been sickle cell disease. Strategies to ensure that the Registry will have adequate resources to meet future requirements include testing selected donors for rare phenotypes and blood conservation programs, such as intraoperative salvage and the treatment of anemia of chronic renal failure with recombinant erythropoietin. PMID- 1448964 TI - Elevated platelet-associated IgG in PlA1-negative mothers following sensitization to the PlA1 antigen during pregnancy. AB - Between 1984 and 1990, we studied 25 infants with neonatal alloimmune thrombocytopenia caused by alloimmunization to the PlA1 alloantigen. We investigated whether mothers of these infants developed elevated platelet associated immunoglobulin (PAIgG) in addition to anti-PlA1. Eight of the women were found to have PAIgG which persistent at least 7-10 days postdelivery. Eluates prepared from six of the women's platelets reacted with PlA1-positive and PlA1-negative donor platelets, and platelets from donors with Glanzmann's thrombasthenia. None of the women with elevated PAIgG had thrombocytopenia, eclampsia, or infections. Two women were found to have autoreactive antibodies present in plasma. These results indicate that elevated PAIgG may be found in women immunized to the PlA1 antigen. Some women may also have autoreactive antiplatelet antibodies in their plasma. These findings may lead to confusing serologic findings in evaluating the cause of neonatal alloimmune thrombocytopenia. PMID- 1448965 TI - A semiautomated method for erythrocyte antigen typing on microtitration plates. AB - We describe a method for erythrocyte antigen typing on U-bottom microtitration plates. This method permitted phenotyping of erythrocytes by an enzyme-enhanced hemagglutination assay simultaneously with an indirect antihuman globulin assay within the same microtitration plate. A robotic sample processor identified the samples, prepared the red cell suspensions and distributed the suspension along with the diluted antisera onto the microtitration plates. The assay results were read and interpreted using a microtitration plate photometer controlled by software specially designed to interpret agglutination reactions. Sample identities and assay results were automatically connected by the computer system and transmitted to a minicomputer system. PMID- 1448966 TI - Complement activation by cold agglutinins. AB - Purified monoclonal human IgM cold agglutinins (CA) of different specificities (anti-I, anti-i, anti-Pr) were investigated for their complement-activating capacity in a homologous system. Incubation of human RBC with excess of IgM CA in the cold, and subsequently with human serum at 37 degrees C, resulted in striking differences in hemolysis. Hemolysis did not correlate to the amount of antibodies bound to RBC at 4 or 20 degrees C. Despite the hemolytic inefficiency of anti-i and anti-Pr CA tested, C1 fixation and subsequent activation of the classical pathway of complement could be assessed in all cases. Absolute numbers of C3 molecules bound to RBC, exceeding the critical level to initiate the terminal sequence of the complement cascade, could not fully explain the differences in the hemolytic activity of the CA. Since C8 binding protein (C8bp) carries I determinants it is hypothesized that anti-I-induced complement-mediated hemolysis might also be favored by the binding of the autoantibody to and probably steric hindrance of this major regulatory protein of the terminal complement sequence. The prominent role of homologous restriction of complement-mediated lysis as a protective mechanism can also be deduced from the fact that rabbit as well as rat serum as a source of heterologous complement lysed cold agglutinin-sensitized red blood cells more efficiently than human serum. PMID- 1448968 TI - Immediate haemolytic transfusion reaction due to anti-Inb. AB - An immediate haemolytic transfusion reaction was investigated in a patient with intestinal cancer. The causative antibody was directed against a high-frequency antigen Inb that was presumably produced as a result of pregnancies. This is the first case of a severe transfusion reaction due to this alloantibody. PMID- 1448967 TI - 11-Oxycorticosteroid-dependent antibody in the serum of a patient with bladder neoplasm. AB - An IgM 11-oxycorticosteroid-dependent antibody was identified in the serum of a patient with bladder malignancy, which at 4-37 degrees C reacted with all the 11 oxycorticosteroids tested but not with desoxycorticosterone, testosterone, nortestosterone and progesterone. The resulting drug-antidrug antibody complex combines nonspecifically with red blood cells causing agglutination. This reactivity is enhanced both by acid pH and by high drug solution concentrations as well as by ficin test. The antibody is complement-independent and has no blood group specificity. No in vivo or in vitro hemolysis was observed. PMID- 1448969 TI - Whole virus lysate or recombinant synthetic ELISA assay to HIV-1: which is better? PMID- 1448970 TI - An example of anti-AnWj causing haemolytic transfusion reaction. PMID- 1448971 TI - Auto-anti-A associated with immune hemolytic anemia. PMID- 1448972 TI - Red cell-bound complement associated with ABO-hemolytic disease of the newborn. PMID- 1448973 TI - [Medical workers and AIDS: the attitude to the problem]. AB - A questionnaire was spread among Kiev physicians with the purpose of evaluating their level of information concerning the AIDS problem. An interrelation of level of knowledge and character of relation to the HIV infection was found. It was established that the idea of air-drop ways of HIV transmission is widely spread among the medical personnel with a tendency to stigmatization of the infected, underestimation of the AIDS problem significance. The authors emphasize the requirement of state-backed program on system of professional training of medical personnel in the AIDS problem. PMID- 1448974 TI - [Problems in improving the public health of a rural area based on a study of statistical data on population health]. AB - The dynamics of health indices of the Khust District (Transcarpathian Province [correction of Zacarpathye region]) population was studied from 1970 through 1990. It is concluded that statistical data on the increase of morbidity are related to improvement of diagnostics of nosological entities related to increase of the availability of doctors, nursing personnel, number of beds in the district. Reserves of further medical services to the population are discussed. PMID- 1448975 TI - [The outstanding Soviet anatomist Mikhail Sergeevich Spirov (on the centenary of his birth)]. PMID- 1448976 TI - [The characteristics of the course of acute pneumonia in patients subjected to prolonged exposure to low doses of ionizing radiation as a result of the accident at the Chernobyl Atomic Electric Power Station]. AB - Distinct changes in the clinical picture of acute pneumonia were noted in patients subjected to constant prolonged (1986-1990) effect of small doses of ionizing radiation as a result of residing in the contaminated territory after the Chernobyl atomic station disaster. These changes included increased duration of the disease, frequency of protracted forms, suppression of the immune system. At the same time a general decrease of the incidence of acute pneumonia, increase of the frequency of severe cases of concomitant pathology indicate some stimulating effect of small doses of ionizing radiation on the body with a healthy immune system and suppressing effect on inadequately functioning immune system. Changes of the clinico-laboratory indices of the course of acute inflammatory process depended on the duration of residing in the contaminated locality and to a lesser degree of the dose. PMID- 1448977 TI - [A scientific knowledge analysis of the problem of the biomedical sequelae of the accident at the Chernobyl Atomic Electric Power Station]. AB - The authors carried out a scientific-research analysis of publication on the problem of medico-biological sequels of the Chernobyl Atomic Station. Systematization of 282 native and 45 foreign publications are presented as information models emphasizing the main trends of research, especially changes in the nervous system as well as in related systems of the body. Further detailed studies of the Chernobyl disaster sequels are important. PMID- 1448978 TI - [The effect of quantum hemotherapy on cellular and humoral immunity and on erythrocyte morphology in patients with ischemic heart disease]. AB - A study is presented of the effect of reinfusions of ultraviolet-irradiated autologous blood on the number of lymphocytes, titer of circulating immune complexes and theophylline-sensitive cells, number of immunoglobulins A, G and M, number and form of erythrocytes in 30 patients with stable and progressive exertion stenocardia. Thirty control patients were treated with nitrates, calcium antagonists and acetylsalicylic acid. It was established that in patients with stenocardia quantum hemotherapy produces an immunocorrective action reduces the titer of circulating immune complexes, the content of T-lymphocytes, the number of immunoglobulins A and G, normalizes the morphological and functional activity of erythrocytes. Use of this method in the treatment of ischemic heart disease is pathogenetically justified and prevents development of myocardial infarction. PMID- 1448979 TI - [Vasodilating agents: the experimental-clinical aspect (a review of the literature)]. PMID- 1448980 TI - [Immunity and the prostaglandin level in gastritis B]. AB - The indices of systemic and local immunity, level of prostaglandins, presence of Helicobacter pylori in the gastric mucosa was studied in 53 patients with gastritis B. Patients with superficial antral gastritis showed independent of the presence of Helicobacter pylori in the gastric mucosa changes of the systemic immunity and level of PGE2 and PGF1 that were abnormal. In atrophy of the antral gastric mucosa and presence there of H. pylori one observed a reduction of the number of T-lymphocytes and proliferative activity. Suppression of the system of prostaglandins in the blood and gastric mucosa, the toxic effect of H. pylori results in autosensibilization, increase of IgA and IgG finally leading to development of erosions in the gastric antrum. PMID- 1448981 TI - [The efficacy of antibacterial treatment in chronic gastritis of Helicobacter etiology]. AB - A study of 140 patients with chronic gastritis revealed Helicobacter pylori in the gastric antral mucosa in 100% and in the duodenum in 50%. There is a direct correlation between the presence and amount of Helicobacter pylori in the mucosa, lymphoplasmocytic infiltration, dystrophic changes of epithelium. Ampiox treatment proved beneficial both clinically and morphologically. After treatment Helicobacter pylori was absent in 65.7%, in the remaining cases it reduced by 5 10 times. PMID- 1448982 TI - [The level and cryoprecipitating activity of fibronectin in bronchial asthma patients]. AB - 125 patients with bronchial asthma were under observation. It has been established that the level of fibronectin decreases as of severity of clinical symptoms of the disease growth. Parallelly cryoprecipitating activity of fibronectin decreases, testifying functional inferiority of the pointed glycoprotein in the patients with bronchial asthma. Under the influence of undergoing therapy restoration of fibronectin concentration and its complex forming ability takes place except of the hormone-dependent cases of asthma. PMID- 1448983 TI - [The erythrocyte composition of the peripheral blood in tobacco smokers]. AB - Data of cytometry and acid erythrography were evaluated in 60 tobacco smokers and 30 non-smoking healthy persons depending on length of smoking. Tobacco smoking was found to effect blood erythrocytes. Five-year smoking resulted in an increase of macrocytes, young resistant cells. Toxic signs were less pronounced concerning the resistance of circulating red cells. 6-10 years duration of smoking resulted in toxic lesions of the circulating erythrocytes confirmed by an increase of the number of spherulation-altered and low-resistant cells, early onset and late termination of hemolysis, increase of the percent of perished cells. PMID- 1448984 TI - [Thrombocyte aggregation in patients with iron-deficiency anemia]. PMID- 1448985 TI - [The use of the HLA phenotype for predicting the outcome of acute glomerulonephritis in adults]. PMID- 1448986 TI - [The dynamics of the urinary glycosaminoglycan indices in the pathogenetic therapy of glomerulonephritis]. AB - A positive dynamics of the course of glomerulonephritis under the effect of pathogenetic therapy evaluated in 140 patients was accompanied by a statistically valid reduction of glycoseaminoglycanes in the urine. This allows to use these indices as adjunctive criteria of treatment efficiency, especially in patients with chronic forms of the disease. PMID- 1448987 TI - [The correction of lipid peroxidation metabolism, the hemostatic system and cerebral hemodynamics in patients with the initial manifestations of cerebral circulatory insufficiency]. PMID- 1448988 TI - [The use of ethonium electrophoresis in treating patients with atherosclerotic encephalopathy]. AB - The new property of ethonium as an angioprotector makes it possible to use ethonium electrophoresis in the treatment of patients with dyscirculatory encephalopathy of atherosclerotic genesis. Treatment results in a hypocholesterolemic effect, improvement of rheoencephalography data and lipid peroxidation. PMID- 1448989 TI - [The hemostatic system in traumatic subarachnoid hemorrhage in the Far North]. AB - It was found that in conditions of the extreme North sanation of the cerebrospinal fluid occurs later in patients with traumatic subarachnoidal hemorrhage than in the central regions of the country. In connection with this the hemostasis system was studied in 20 patients with traumatic subarachnoidal hemorrhage and 10 patients with brain tumours (control group). Patients with traumatic subarachnoidal hemorrhage showed significant hypocoagulation changes. PMID- 1448990 TI - [The clinico-physiological validation of the use of the endolymphatic route for antibiotic administration for preventing the translocation of intestinal microflora during the treatment of sepsis patients]. AB - One of the main mechanisms of generalization of infection in purulent inflammatory processes of the abdominal cavity, retroperitoneal space and pelvis minor is translocation of the pathogenic microflora of the intestine in the lymphatic system via regional lymphatic nodes with subsequent rupture into the systemic circulation. Endolymphatic administration of antibacterial agents into the peripheral lymphatic vessel favours saturation of the reticuloendothelial structures of the lymph nodes by the antibiotic agent that increases their barrier function and, thus, prevents generalization of the infection and development of polyorganic insufficiency. PMID- 1448991 TI - [An electron microscopic study and the morphofunctional status of the lungs in an experimental reproduction of acute pneumonia]. AB - An analysis of the ultrastructural organization of alveocytes (types I and II), endotheliocytes, interstitium alveolar, macrophages and aerohematic barrier in rabbits with experimental acute pneumonia revealed disorders of synthesis and release of surfactant on the alveolar surface. The observed in pneumonia edema and swelling of the aerohematic barrier components as well as the interstitium reduces the protective mechanism of alveols favouring transition of the disease to a protracted form. PMID- 1448993 TI - [The methodological aspects of studying brain bioelectrical activity in exposure to electromagnetic factors]. PMID- 1448992 TI - [The effect of elevated environmental temperature on the development of a potassium deficiency in the body]. AB - Electron microscopy and roentgen microanalysis were used to study the ultrastructure and electrolytic balance of K+, Na+ and Cl- of the animal myocardial tissue during general body hyperthermia. It was established that long term effect of heating microclimate causes a distinct reduction of K+ in the cardiomyocytes accompanied by essential changes of the ultrastructure of ischemic character. PMID- 1448994 TI - [The toxicological-hygienic characteristics of surface-active substances used in the technological processes of the oil-producing industry]. AB - The authors suggest two stages of ecological and hygienic evaluation of surface active substances widely used in oil extraction. Stage 1. Toxicological-hygienic evaluation of these substances. Stage 2. Ecological-hygienic aspects of surface active substances (migration into soil, phytotoxicity, effect on the water quality and oth.). It was established at stage 1 that proxanol, proxamin, diproxamin are compounds of minor hazard (class 4 hazard). These substances belong to local skin-irritating substances. Proxanol produces skin-resorptive effects which is confirmed by clinical signs of intoxication, reduction of weight of the experimental animals. PMID- 1448995 TI - [The peripheral hemodynamics of pregnant women with diabetes mellitus]. AB - The state of the peripheral hemodynamics was studied rheovasographically in 26 pregnant patients suffering of diabetes mellitus and 30 healthy pregnant (pregnancy terms: 26, 27 and 34-40 weeks). Results of the study revealed changes of the peripheral hemodynamics in the pregnant diabetic patients as compared with pregnant women non-diabetics. These changes consisted in non-adequate response of the vascular bed to increased hemodynamic loads at the 27-33 pregnancy week as well as in more significant increase of the tone in the diabetic patients during the first half of pregnancy as compared with the healthy women. These changes may become supplementary criteria for revealing preclinical manifestations of diabetic angiopathies in pregnant diabetic women. PMID- 1448996 TI - [Natural killer activity--an index of treatment efficacy in patients with acute leukemia]. AB - Treatment results were analyzed in 60 patients with acute non-lymphoblastic leucosis. In 30 patients treatment was carried out with consideration of sensitivity of blast cells to chemotherapeutic agents, in 30 polychemotherapy programs were used. Results indicate that individual choice of agents produced a large number of complete clinico-hematological remissions. In 50% of patients with clinico-hematological improvement natural killers were found in the blood and they showed activity after a course of selected treatment. PMID- 1448997 TI - [The effectiveness of dispensary treatment to prevent myocardial infarct and its mortality]. PMID- 1448998 TI - [The comprehensive diagnosis and treatment of lymphosarcoma of the pharynx]. AB - Modern methods (intrascopic and other instrumental) were used to increase the diagnostic efficiency and extension of the tumour process in 22 patients with lymphosarcoma of the pharynx. Optimal treatment efficacy is achieved in lymphosarcoma of the pharynx by combined use of surgical, radiation (non traditional course) treatment as well as chemotherapy which is used at early stages as an adjunctive method. PMID- 1448999 TI - [Multiple and multilevel compression radiculoneuropathies]. PMID- 1449000 TI - [The rehabilitative treatment of patients after a myocardial infarct who reside in an area close to the Chernobyl Atomic Electric Power Station]. AB - Rehabilitation treatment is evaluated in 55 patients (long-term results) with a history of myocardial infarction residing in the Chernobyl atomic station zone. It was established that the course of the disease in persons who participated in liquidation of the Chernobyl disaster was characterized by a more frequent development of reinfarctions as compared with the Kiev population. Patients residing in the zone neighbouring the Chernobyl station developed more frequently cardiac failure. This requires detailed examination of these patients during their return to work. PMID- 1449001 TI - [The clinical picture of thallium poisoning and the late sequelae]. PMID- 1449002 TI - [The significance of the lymphocyte adherence inhibition test in patients with diffuse toxic goiter]. AB - Patients with diffuse toxic goiter reveal an increased adhesive capacity of lymphocytes evidencing a reduction of lymphokine production by lymphocytes which would suppress adhesiveness. The degree of increase of adhesive properties of lymphocytes depended on the severity of the clinical picture of diffuse toxic goiter, being higher in those with a severe course. Results of the test of lymphocyte adhesion suppression reflect the state of cellular immunity, severity of the clinical course of diffuse toxic goiter and efficacy of treatment. PMID- 1449003 TI - [Occupational morbidity among the workers in enterprises for secondary ferrous metal processing and in refractory materials plants]. AB - The authors discuss the level of professional morbidity among workers of ferrous metal processing enterprises and of refractory factories depending on the profession, age, length of work and sex. Recommendations on the reduction of professional diseases in this branch of industry are given. PMID- 1449004 TI - Prognostic indicators in fulminant hepatic failure. AB - Because of the inhomogeneous prognosis in fulminant hepatic failure, prognostic criteria are required which help to establish the indication for liver transplantation as a successful therapeutic procedure. In our study of 33 patients with fulminant hepatic failure (94% viral hepatitis, 67% hepatitis B), serum bilirubin > 320 or < 160 mumol/L, serum creatinine > 110 mumol/L, prothrombin time < 15% of the normal value and duration of jaundice until onset of encephalopathy > 7 days indicated a fatal outcome. When criteria described by O'Grady et al. were used, only limited predictability was achieved. This, as well as the frequently contradictory results of the few prognostic studies published so far, is probably due to the regional differences in the etiology and the different clinical courses of fulminant hepatic failure. PMID- 1449005 TI - [Orthotopic liver transplantation in hepatic cirrhosis: on the problem of infection of the transplant with persistent hepatitis viruses]. AB - 269 orthotopic liver transplantations (OLT) were performed in 253 patients at our institution from September 1988 to May 1992. 121 patients had end-stage cirrhosis secondary to viral hepatitis type B, delta, or type non-A non-B and C respectively. Reinfection of the graft by persistent viruses is a potential complication in these cases. Passive immunization with anti-HBs hyperimmunoglobulin (HIg) can prevent clinically relevant reinfection of the graft in patients with hepatitis B virus (HBV) infection and low replication rates. Patients with high replication rates will rarely benefit from OLT. Patients with hepatitis delta virus (HDV) infection usually experience HDV reinfection of the graft with subsequent chronic hepatitis although prophylaxis with anti-HBs-HIg was performed. Treatment with interferon alpha had no apparent effect on the incidence of graft reinfection with HBV in this series, but the replication rate of HDV was reduced. Persistent hepatitis C viruses (HCV) usually infect the graft; this was demonstrated in 17 patients by means of the polymerase chain reaction. HCV infection usually causes a mild form of acute hepatitis with transition to a chronic course. Therefore the significance of persistent viral infection lies in the potential for chronic hepatitis in the transplanted organ rather than in the danger of acute injury of the allograft. PMID- 1449006 TI - [Extraction of an artery in rectal biopsy]. AB - A biopsy of a rectal carcinoma has led to the extraction of a 2.5 cm arterial specimen, followed by an arterial bleeding. The cause of this exceptional complication was the presence of atypical vessels reaching the rectal lumen due to tumor ulceration. PMID- 1449007 TI - [Risk of colorectal cancer in ulcerative colitis--monitoring strategies and identification of risk patients]. AB - Patients with ulcerative colitis carry an increased colorectal cancer risk. The cumulative cancer risk for patients with pancolitis is 0.5-0.7% per patient year. Dysplasia as a histologic marker of a neoplastic transformation is used to identify patients with an increased cancer risk during colonoscopic surveillance. Because the classification of dysplasia is subject to inter- and intraobserver variation new methods for the detection of risk patients have been investigated. DNA analysis by flow cytometry seems to be of value for the detection of DNA aneuploidy and the identification of patients who are at risk for neoplastic progression. The significance of DNA aneuploidy is being evaluated in prospective studies. Surveillance guidelines depend on duration and anatomical extent of the colitis as well as on the detection of dysplasia. PMID- 1449008 TI - [Ultrasound morphology of gallstones]. AB - Using a subtile examination technique genuine information can be obtained from the interior of a gallstone--at least to a depth of 15 mm. This information should provide an indication of the homogeneous (crystalline) or inhomogeneous (non-cholesterol) structure of the stone. Further systematic use of differentiating gallstone ultrasonography could become a useful additional decision making criterion for selection of gallstones suitable for conservative treatment. PMID- 1449009 TI - ["Idiopathic pancreatitis"--sludge as the most common cause?]. PMID- 1449010 TI - [Biliary pain in bile ducts without calculi: where is the error?]. PMID- 1449011 TI - [Pathogenesis of liver fibrosis. Synthesis of collagen and non-collagen proteins in cell culture and in vivo]. AB - In vitro and in vivo studies have shown that Ito-cells are able to express the "smooth-muscle"-isoform of alpha-actin which seems to characterize the activated stage of the cells. "Activated" Ito-cells synthesize and secrete collagen- and non-collagen components of the extracellular matrix like fibronectin, laminin, tenascin and entactin. "Quiscent" Ito-cells synthesize mostly collagen type IV and III while "activated" Ito-cells also synthesize alpha-2-macroglobulin, a potent protease inhibitor. The in vitro obtained results were confirmed in vivo as demonstrated on liver sections from chronically damaged liver (carbon tetrachloride administration) by immunohistochemistry and by in situ hybridisation technique. Sinusoidal endothelial cells were shown to synthesize collagen type IV and fibronectin during the time in culture. PMID- 1449012 TI - [Pathomorphology of acute and chronic stages of CCl4-induced liver fibrosis: immunohistochemical and in situ hybridization studies]. AB - The cellular localization of expression of various genes activated during the course of liver fibrosis and regeneration was studied by immunohistology and in situ hybridization in rat and human liver tissues. Mesenchymal cells proved to be the principal sources of extracellular matrix proteins and of fibrogenic growth factors, whereas the collagenase-activating protease transin/stromelysin gene was transcribed in parenchymal cells as well. Fibrogenesis by the mesenchymal compartment appears to be balanced by fibrolysis controlled by parenchymal cell functions. Continuous parenchymal damage may thus disrupt this balance between fibrogenesis and fibrolysis, resulting in fibrosis. PMID- 1449013 TI - [Connective tissue polypeptides in serum: new parameters of connective tissue synthesis and degradation in liver fibrosis]. AB - With the invention of drugs that effectively and specifically inhibit excessive collagen synthesis in the liver, a growing interest in serum assays that assess fibrogenesis, i.e. the de novo formation and fibrolysis, i.e. the removal of connective tissue in the liver, may be anticipated. Several serum assays for connective tissue polypeptides fulfil the criteria of sensitivity and specificity for chronic liver diseases. The aminoterminal procollagen type III peptide (PIIINP) correlates with hepatic fibrogenesis, whereas the propeptides of basement membrane collagen (PIVNP and PIVCP) and the basement membrane glycoprotein laminin reflect the enhanced turnover of basement membranes of the sinusoids as well as of proliferating bile ducts and blood vessels in active fibrosis. Circulating collagen type VI results from degradation of interstitial microfilaments and undulin appears to be released upon remodeling of the hepatic architecture. Combined measurement of selected parameters may allow a non invasive assessment of the balance between fibrogenesis and fibrolysis on a day to-day basis, especially in the light of potential antifibrotic therapy. PMID- 1449014 TI - Pharmacokinetics of colchicine: a review of experimental and clinical data. AB - Thanks to the development of a sensitive and specific radioimmunoassay for colchicine, the pharmacokinetics of colchicine is now well-established after single oral doses. Absorption is characterized by a zero-order rate constant while disposition appears biexponential with a rapid distribution phase (t1/2 = 1.8 h) and a long elimination phase (t1/2 = 20 h). All studies confirm the large total body clearance (35 l/h) predominantly by the extrarenal route and the large distribution volume (700 l). Further studies need to be performed to investigate colchicine absorption and to describe the metabolic pathway of the drug. To date, relationships between colchicine plasma levels and pharmacological effects have not been defined. Monitoring of plasma levels in patients with familial Mediterranean fever should improve treatment with colchicine. However, the therapeutic range has not been precisely determined. The use of colchicine in the treatment of liver cirrhosis and primary biliary cirrhosis is a recent development; so, assuming that a large part of total body clearance depends on hepatic function, the influence of hepatic diseases on colchicine disposition needs to be investigated in order to define the most appropriate therapeutic dosing. PMID- 1449015 TI - [Colchicine in toxic liver cirrhosis and primary biliary cirrhosis]. AB - In animals, colchicine has been shown hepatoprotective, which is related to its anti-fibrotic and anti-inflammatory effect. In man, colchicine has been used for the treatment of alcoholic liver disease and primary biliary cirrhosis. Although controlled trials observed an improvement of liver function tests under colchicine, the survival rate in most studies was only slightly improved without reaching statistical significance. Therefore, at present, no final evaluation of colchicine for the treatment of alcoholic liver diseases and primary biliary cirrhosis can be given. PMID- 1449016 TI - [Pathophysiology of cholestasis: correlation between bile acid metabolism and liver damage]. AB - In patients with cholestasis the biliary excretion of bile acids is diminished. Hepatic sulfation, glucuronidation and hydroxylation of bile acids are increased and enhance their urinary excretion. These metabolic pathways however, are not sufficient to prevent hepatic damage by bile salts. Ursodeoxycholic acid, a very hydrophilic and therefore untoxic bile acid, in part prevents the hepatotoxicity of more hydrophobic bile acids. PMID- 1449017 TI - Treatment of chronic active hepatitis and primary biliary cirrhosis with ursodeoxycholic acid. AB - Ursodeoxycholic acid (UDCA) improves liver function tests in patients with chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC). UDCA will reduce biochemical parameters of both cholestasis and hepatocellular damage. The effects may be less beneficial in patients with advanced stages of chronic liver disease: in PBC we found the improvement of laboratory parameters in stage I and II very impressive, in stage III and IV it was less marked. Data of two controlled trials in PBC showed an improvement in liver histology, in one study the improvement was statistically significant. UDCA can be administered for at least 10 years without any adverse effects, the treatment is safe and improves life quality. The mode of action of UDCA seems to be in its displacement of toxic hydrophobic bile salts from the bile acid pool and the hepatocellular membrane. In in-vitro investigations a direct protective effect of UDCA on isolated sinusoidal hepatocyte membranes against toxic bile salts has been shown. This protective effect of a more general nature may explain the efficacy of UDCA in different chronic, especially cholestatic liver diseases. PMID- 1449018 TI - Hepatic fibrogenesis: the puzzle of interacting cells, fibrogenic cytokines, regulatory loops, and extracellular matrix molecules. AB - Fibrotic lesions affect a wide variety of organs but liver fibrosis is probably the most abundant form of organ fibrosis. Disturbances of the equilibrium between parenchyma and extracellular matrix (ECM) leading to a disproportionate increase and irregular deposition of newly formed connective tissue components (fibrosis) is a common and clinically most important sequelae of chronic active liver diseases. Significant progress has been made during the last years in the analysis of the structural composition of ECM in normal and fibrotic liver and in the dissection of the molecular and cellular mechanisms of exaggerated ECM deposition in necroinflammatory areas using experimental models of hepatic fibrosis, isolated cells in mono- and coculture systems and the growing repertoire of molecular biological tools. Perisinusoidal, retinoid-storing cells (Ito cells, parasinusoidal lipocytes) transform under inflammatory stimuli to myofibroblast-like cells being qualitatively and quantitatively the most important connective tissue producing cell type in human and animal liver. Its activation and transformation is mediated by paracrine and autocrine loops involving transforming growth factor (TGF) beta as the main fibrogenic mediator secreted by activated liver macrophages, possibly also by endothelial cells and liberated by disintegrated thrombocytes. In advanced stages of retinoid-storing cell transformation additional growth factors like platelet derived growth factor (PDGF) become important indicating a sequential action of cytokines and fibrogenic mediators during the fibrogenic process. The molecular and cellular interactions in the course of liver fibrogenesis have gained model character for a number of other organ fibrotic processes, wound repair, and atherogenesis included.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449019 TI - [Combined ursodeoxycholic acid plus colchicine--treatment of primary biliary cirrhosis: results of a placebo-controlled double-blind study]. AB - In the present pilot study we investigated the effects of urso treatment alone in comparison to a combined treatment with urso plus colchicine in PBC. 22 patients with PBC in the histological stages 1-3 entered the study. All patients were pretreated with urso alone (10-12 mg/kg) for 12 months. Thereafter treatment was continued in a double-blind randomized fashion with urso plus placebo or urso plus colchicine (1 mg/day) for another 12 months. During the initial 12 months urso treatment liver function tests improved significantly in all patients, pruritus improved in 60% of patients. After randomization to the different treatment groups the biochemical parameters stabilized at the lower level and no significant differences could be found between urso plus placebo and urso plus colchicine treatment concerning aminotransferases, alkaline phosphatase, bilirubin, cholinesterase, albumin or cholesterol. The results of this pilot study suggest that the addition of colchicine to an initial urso treatment does not lead to further improvement of aminotransferases, alkaline phosphatase, bilirubin or clinical symptoms like pruritus. PMID- 1449020 TI - [The dependence of respiratory intensity on body mass in representative Caudata and Salientia]. AB - Experimental data indicate dependence of the respiration rate on the body mass in both caudate and ecaudate amphibians. The regression line slopes are similar in the both groups, while the a factor value is 3 times lower in the caudates than it is in ecaudates. There certain sex differences in the respiration rate which have no clear biological interpretation. PMID- 1449021 TI - [The motor activity of the chick embryo amnion in the late stages of development. The role of serotonin and noradrenaline]. AB - Experiments with 13- to 19-day-old chicken embryos maintained at 37 degrees C were conducted using direct registration of embryonic movements and amnion pulsation. It is shown that in the non-innervated and lacking blood vessels non striated-muscled amnion, motoric activity could be observed nearly up to the end of the embryonic development, not only during 5 to 14 days old interval as it was supposed earlier. In accordance with our previous results indicating important role of biogenic amines (serotonin and noradrenaline) in the regulation of motoric activity of the chicken embryo amnion at earlier and middle ages, this study provides some evidences of the humoral regulatory mechanism even at later embryonic stages. After being injected into amniotic fluid of older embryos, the serotonin stimulates and noradrenaline inhibits amnion motoric activity (the both are taken at final concentration of 10(-7) to 10(-6) M). Serotonin's receptors blocator, the cyprogeptadin, suppress while beta-adrenoreceptors' blocator, the propranolol, activates intact amnion motorics ( both are taken at final concentration of 10(-7) to 10(-5) M). PMID- 1449022 TI - The European Federation of Cytology Societies, 1969-1989. PMID- 1449023 TI - Diagnosis of follicular lymphoma by fine needle aspiration biopsy. AB - This study evaluated the diagnostic accuracy of fine needle aspiration biopsy (FNAB) of follicular lymphoma (FL). Fourteen aspirates of lymph nodes in which follow-up surgical biopsy revealed FL were studied. Two aspirates were deemed unsatisfactory because of a paucity of cells. The remaining 12 cases received the following diagnoses: 4 positive for malignant lymphoma, 4 highly suspicious for malignant lymphoma and 4 false negatives. FNAB of FL can show a monomorphic or polymorphic cell population. The aspirates with a positive or suspicious diagnosis showed monomorphic cell populations. False-negative diagnoses were attributable to misleading sampling or preparation methods in most cases. We conclude that FNAB of FL is less accurate than FNAB of non-Hodgkin's malignant lymphoma (NHL) in general, but the accuracy rate is similar to that of FNAB of all low-grade NHL. The value of current approaches to the diagnosis of suspected lymphoma by FNAB is emphasized. PMID- 1449024 TI - Comparison of cellular phenotypes in tumor cyst and ascitic fluid from ovarian serous carcinoma. AB - Density gradient centrifugation was applied to isolate cell subsets from tumor cyst and ascitic fluid in eight patients with ovarian serous carcinoma. A comparison of cellular composition and immunologic reactivity of cells from the cysts and from ascitic fluid in each patient was performed. Some differences in density profiles were found, but in each case the consistency of morphologic cell forms in the primary tumor and ascites was documented. Immunophenotypic analyses of isolated cellular fractions using polyclonal and monoclonal antibodies against ovarian carcinoma-associated antigens showed significant immunologic intratumoral heterogeneity. However, there was a similarity of antigen expression in cells from the primary tumors and ascitic fluids. Our study indicated that morphologic and antigenic characterization of a given tumor could be determined in a single representative sample of ascitic fluid. PMID- 1449025 TI - Influence of endocervical status on the cytologic prediction of cervical intraepithelial neoplasia. AB - A case-control analysis of the endocervical status of smears that preceded a histologic diagnosis of cervical intraepithelial neoplasia (CIN) showed that smears which correctly predicted CIN were significantly more likely to include metaplastic cells than were smears reported to be negative. There was no significant difference between the smears with respect to the presence of columnar cells. A high level of agreement was apparent between scientists in determining both columnar and metaplastic cell status. A discussion of the definition, role and potential impact of endocervical status in the prevention of cervical cancer is presented. PMID- 1449026 TI - Fine needle aspiration of pancreatic cystic epithelial neoplasms. AB - Pancreatic cystic epithelial neoplasms present diagnostic challenges in cytology. An accurate diagnosis is important since the prognosis and treatment may vary. We report the cytologic features in fine needle aspirates of four cases of cystic neoplasms of the pancreas (two micro-cystic adenomas, one mucinous cystic neoplasm and one mucinous cystadenocarcinoma). Smears were evaluated as to their cellularity, content and predominant cell type. Aspirates from the microcystic adenomas yielded hypocellular material with rare strips of cuboidal cells having bland nuclei and pale cytoplasm. No mucinous material was identified in the background, but the cells stained positively with periodic acid-Schiff stain. Smears from the mucinous cystic neoplasm were moderately cellular and contained abundant mucinous material. The columnar epithelial cells were arranged in tight sheets, clusters and strips. Most cells had benign nuclear features with focal mild nuclear atypia. Key cytologic findings noted in the mucinous cystadenocarcinoma were moderate cellularity, loose clusters of cells, single cells, overt malignant nuclear features and occasional signet ring cells. Pancreatic pseudocysts can be distinguished from pancreatic cystic epithelial neoplasms by the predominance of histiocytes and inflammatory cells and absence or paucity of epithelial cells. To differentiate microcystic adenomas from mucinous cystic neoplasms, the above criteria coupled with periodic acid-Schiff and mucin staining should effectively differentiate these diagnostic entities. PMID- 1449027 TI - Fine needle aspiration of lymphoblastic lymphoma. A multiparameter diagnostic approach. AB - Sixteen fine needle aspiration (FNA) biopsies of lymphoblastic lymphoma (LBL) that were used to either initially diagnose disease (12) or document relapse (4) were reviewed. Cellular aspirates (2 x 10(7) cells) were readily obtained for immunologic, DNA/RNA flow cytometric and immunoglobulin and/or T-cell receptor gene rearrangement studies. Cytologically, aspirates were characterized by intermediate-sized cells (9.5-18.5 microns) with fine nuclear chromatin, small, inconspicuous nucleoli, irregular nuclear contours and scant basophilic cytoplasm. Frequent mitotic figures were seen (1-14 figures per 1,000 cells). Fourteen cases demonstrated a T-cell phenotype with considerable phenotypic variability. One case demonstrated a precursor B-cell phenotype, and another demonstrated biphenotypic expression with both T-cell and myeloid differentiation. Eleven of 14 cases (79%) were positive for terminal deoxynucleotidyl transferase. Thirteen of 15 cases (87%) manifested diploid DNA content by flow cytometric analysis and were characterized by intermediate proliferative activity (S+G2M 12.7 +/- 8.7% SD) and intermediate mean RNA index (1.3 +/- .5 SD). T beta gene rearrangements were demonstrated in four of five phenotypic T-cell LBL cases analyzed, with concomitant JH gene rearrangements observed in three cases, confirming that bigenotypic rearrangements characterize some T-cell LBLs. We conclude that FNA samples are adequate for accurate characterization of LBL and may obviate the need for surgical biopsy. PMID- 1449028 TI - Cytopathology of the tall cell variant of thyroid papillary carcinoma. AB - The tall cell variant of thyroid papillary carcinoma differs from classic papillary carcinoma in its more aggressive clinical behavior, cell type (columnar amphophilic to oxyphilic) and higher frequency of stromal lymphoid infiltrate. A retrospective study of three such cases was made, with an emphasis given to the utility of fine needle aspiration cytology in their identification. Aspirates revealed papillary fronds and cyanophilic and oxyphilic neoplastic cells with a high proportion of nuclear grooves and cytoplasmic inclusions. These nuclear details allowed a specific diagnosis of papillary carcinoma with oxyphil cells as compared to oxyphilic cell follicular tumors. Smears from two cases showed, in addition, lymphoid cells and multinucleate giant cells. In them a diagnosis of coexisting Hashimoto's disease, granulomatous thyroiditis or inflammatory tumor stroma could not be excluded cytologically. PMID- 1449029 TI - Fine needle aspiration cytology of primary soft tissue tumors. Morphologic analysis of the most frequent types. AB - We reviewed 98 cases of fine needle aspiration of soft tissue tumors with histologic confirmation performed during an eight-year period and propose a working morphologic classification based on the most prominent cytologic features. Six main tumor groups are recognized: myxoid, round cells, spindle cells, pleomorphic cells, polygonal cells and well differentiated. We believe that this classification allows recognition of the most common soft tissue tumors while helping with the differential diagnosis of other neoplasia, primary or secondary, with similar morphology and a similar presentation. PMID- 1449030 TI - Cerebrospinal fluid cell preparation methods. An evaluation. AB - Although the cells from cerebrospinal fluid are widely used for diagnostic purposes, the cell yield on the microscopic slide is only rarely considered and mostly unsatisfactory. A reevaluation of several preparatory methods showed a very low yield with the Sayk-type chamber, a modest yield with the cytocentrifuge and the best yield with a simple, self-adhering chamber on slides coated with a polycation. PMID- 1449031 TI - Presacral myelolipoma. Report of a case with fine needle aspiration cytology and immunohistochemical and histochemical studies. AB - The cytomorphologic features of a case of the rare presacral myelolipoma, diagnosed by computed tomography (CT)-guided percutaneous fine needle aspiration (FNA) biopsy, are presented. It occurred in a 40-year-old man on prolonged steroid therapy for bronchial asthma. On the air-dried, Diff-Quik-stained smear, hematopoietic cells of all lineages and fragments of collapsed stroma were seen in a background of fat droplets. Megakaryocytic, myelocytic and eosinophilic lineages were further demonstrated by Factor VIII immunostain, chloroacetate esterase and LUNA-E histochemical stain, respectively. The reticulum stain of the resected tumor demonstrated that the hematopoietic cells and fat were supported by numerous reticulum fibers of varying thickness; that accounted for the collapsed stroma in the aspirated material. Presacral myelolipoma, occurring predominantly in female adults and presenting secondarily as a space-occupying lesion, is best regarded as encapsulated, heterotopic bone marrow supported by a network of reticulum fibers; it has a characteristic image on CT scan and can be diagnosed by FNA. PMID- 1449032 TI - Fine needle aspiration cytology of clear cell sarcoma. Report of a case with immunocytochemical, immunohistochemical and ultrastructural studies. AB - Cytologic findings of clear cell sarcoma obtained by fine needle aspiration (FNA) of a tumor are described. The tumor probably originated in the retroperitoneal tissue, and the diagnosis was confirmed histologically by open biopsy. Percutaneous needle aspirates of the intraabdominal tumor and touch preparations obtained from the open biopsy specimen revealed numerous atypical cells with an extremely hyperchromatic nucleus, prominent nucleoli and clear cytoplasm. The cytoplasm was rich in glycogen. The immunocytochemical technique demonstrated S 100 protein and neuron-specific enolase in the cytoplasm, both of which were exhibited also in the histologic specimen. Clear cell sarcoma is a rare tumor of soft tissue, and to our knowledge, detailed cytologic appearances of this tumor obtained by FNA have not been reported. In addition, the present tumor was unique in location. It is possible to diagnose clear cell sarcoma accurately on an FNA cytologic specimen if the periodic acid-Schiff stain and immunocytochemical technique are utilized in addition to the routine Papanicolaou method. PMID- 1449033 TI - Cytology of pyelitis glandularis cystica. A case report. AB - Cytologic findings that occur in association with proliferative lesions involving von Brunn's nests in the urinary tract are rare. Such lesions are probably far more common than recognized and are probably considered in the clinicoradiologic differential diagnosis when space-occupying lesions are found, particularly in the upper urinary tract. Reported here are the cytologic findings in a case of pyelitis glandularis cystica that presented as a renal pelvic lesion. PMID- 1449034 TI - Transitional cell carcinoma of the renal pelvis metastatic to the metacarpal. A case report correlating cytologic and histologic findings. AB - This report describes the cytologic, radiologic and histologic findings in a 76 year-old male who presented with a pathologic fracture of the first metacarpal bone as the result of metastatic transitional cell carcinoma. The primary neoplasm was sited in the right renal pelvis. Metastases were also detected in the liver and confirmed cytologically. Problems encountered with the cytologic diagnosis are explained by correlation with the histologic findings. The case also illustrates the importance of clinicopathologic correlation when interpreting fine needle aspiration biopsies. PMID- 1449035 TI - Adamantinoma. A case report with aspiration cytology and differential diagnostic and immunohistochemical considerations. AB - Fine needle aspiration biopsy of bone lesions is routinely used in the metastatic workup of patients with radiographically suspicious areas. However, caution must be used when interpreting smears from aspirates performed on primary bone neoplasms. These tumors are often heterogeneous, and problems with sampling may be encountered. We report a case of a 25-year-old male who presented with a 3-cm lytic lesion in the tibia. A diagnosis of benign fibroosseous lesion was based on the clinical presentation, radiographic appearance and presence of numerous sheets and single cytologically bland spindle cells. Subsequent curettage of the specimen revealed an adamantinoma with a prominent fibrous component. Most of these rare, locally aggressive neoplasms are located in the tibia. They are characterized histologically as having a fibrous background with islands of basaloid, spindle or squamoid cells. Furthermore, a differentiated, regressing variant with an osteofibrous dysplasia-like appearance also exists. Smears consisting primarily of spindle cells or fibrous tissue may lead to an erroneous diagnosis of a fibrohistiocytic neoplasm, fibrous dysplasia, fibrous cortical defect or ossifying fibroma. Pertinent cytomorphologic features should aid in establishing the correct diagnosis of adamantinoma. PMID- 1449036 TI - Cytodiagnosis and comparison of nondecidualized and decidualized endometriosis of the abdominal wall. A report of two cases. AB - We describe two cases of endometriosis of the abdominal wall occurring in young, multiparous women in which the diagnosis was made by fine needle aspiration biopsy. One case illustrates the cytologic features of non-decidualized endometriosis: a biphasic population of stromal and glandular cells. In contrast, the other case showed large, plump stromal cells in a distinctive myxoid background, creating a picture of decidualized endometriosis. The differential diagnoses of palpable masses in the abdominal wall and the importance of clinicopathologic correlation are discussed. PMID- 1449037 TI - Cytologic and immunocytochemical studies of cerebrospinal fluid in meningeal sarcoidosis. A case report. AB - Serial studies were done on cerebrospinal fluid (CSF) from a patient with sarcoidosis involving the meninges. Initially when the disease was active, the CSF protein was increased and glucose decreased. The number of cells in the CSF was moderately increased, and many mononuclear cells were present. Cytologic studies of the CSF showed many normal and some atypical lymphocytes. Immunochemical studies showed that most of these lymphocytes were T cells, with T helper cells predominating over T-suppressor cells by a ratio of 3.92; B lymphocytes were polyclonal. Subsequent studies of the CSF over the following three and one-half years showed that the protein and glucose content and the cell counts in the fluid did not correlate well with the activity of the disease. The number of atypical lymphocytes seemed to be a more useful marker of disease activity in the patient. Cytologic studies, when interpreted within the context of other CSF and clinical findings, are useful for the assessment of patients with sarcoidosis involving the meninges. PMID- 1449038 TI - Proficiency testing in gynecologic cytology. PMID- 1449039 TI - The relationship between first-phase insulin secretion and glucose metabolism. AB - A possible pathogenetic link between absence of first-phase insulin secretion and development of impaired glucose metabolism has been suggested by the results of several cross-sectional studies. First-phase insulin secretion measured during a +7 mmol/l hyperglycemic glucose clamp correlated with total glucose disposal during the clamp (r = 0.65, p < 0.001, N = 59). To examine whether restoration of first-phase insulin secretion improves peripheral glucose uptake in subjects with impaired glucose utilization, seven insulin-resistant subjects (age 54 (38-62) years: BMI 29.3 (21.7-35.8); fasting plasma glucose 5.5 (4.8-7.2) mmol/l; fasting insulin 57 (37-105) pmol/l with impaired first-phase (148 (29-587) vs controls 485 (326-1086) pmol/l x 10 min; p < 0.05) and normal second-phase (1604 (777 4480) vs controls (1799 (763-2771) pmol/l x 110 min) insulin secretion were restudied. The impaired first-phase insulin secretion was restored by an iv insulin bolus at the start of the hyperglycemic clamp. Substrate oxidation rates and hepatic glucose production were determined by indirect calorimetry and [3 3H]glucose infusion. Total glucose uptake was impaired in the insulin-resistant subjects with impaired first-phase insulin secretion compared to controls (18.8 (13.2-22.2) vs 34.8 (24.3-62.1) mumol.kg-1 x min-1; p < 0.01). Restoration of first-phase insulin secretion (1467 (746-2440) pmol/l x 10 min) did not affect glucose uptake (20.2 (9.9-23.8) mumol.kg-1.min-1), with no difference in oxidative and non-oxidative glucose metabolism between the experiments. Second phase insulin secretion was similar during both experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449040 TI - Parathyroid hormone-related peptide, measured by a midmolecule radioimmunoassay, in various hypercalcaemic and normocalcaemic conditions. AB - The diagnosis of humoral hypercalcaemia of malignancy often presents considerable clinical problems. We have studied parathyroid hormone-related peptide (PTHrP) in serum from patients with humoral hypercalcaemia of malignancy (N = 22), hypercalcaemia of malignancy with skeletal metastases (17), histologically confirmed primary hyperparathyroidism (21) and hypercalcaemic patients with various benign diseases (9). PTHrP measurements were also made in normocalcaemic patients with various malignancies (23), endocrine diseases (13), sarcoidosis (22) and chronic renal failure (17). PTHrP was measured by a novel radioimmunoassay using rabbit antibodies directed towards the midregion of the molecule. Immuno- or silica cartridge extraction of serum before radioimmunoassay enabled us to measure PTHrP in all samples, which may add further information about circulating forms of PTHrP. PTHrP was clearly elevated in patients with humoral hypercalcaemia of malignancy (5.0 +/- 4.7 pmol/l) (mean +/- SD, N = 12) and when the kidney function was impaired (4.0 +/- 0.9 pmol/l) (N = 15) (silica cartridge extraction), whether the subject was hypercalcaemic or not. Some patients with endocrine diseases, including two with primary hyperparathyroidism, had slightly elevated serum PTHrP concentrations, while they were normal in sarcoidosis. In healthy subjects the levels were 1.1 +/- 0.5 pmol/l (N = 15) after immunoextraction and 0.8 +/- 0.2 pmol/l (N = 33) after silica cartridge extraction. PMID- 1449041 TI - Treatment of juvenile goitre with levothyroxine, iodide or a combination of both: the value of ultrasound grey-scale analysis. AB - The effects of oral iodide, levothyroxine and of iodide and levothyroxine in combination were studied in three groups of 30 children, age 13-15 years, with euthyroid goitre. As endpoints of this study, we used thyroid volume reduction, thyroid hormones, thyrotropin and thyroid grey-scale histograms by computerized analysis. The three groups were well matched with respect to mean age, body weight and pretreatment thyroid volumes and thyroid hormones. Mean urinary iodide excretion before treatment was in the range of 30 micrograms/g creatinine, since the study was conducted in an iodine-deficient area. All three treatment regimens led to significant reductions in thyroid volume within one month. After six months on 100 micrograms of levothyroxine, thyroid volume had decreased from 14.1 +/- 4.2 ml to 8.3 +/- 2.6 ml (mean +/- SD); on 150 micrograms of iodide, from 18.5 +/- 6.2 ml to 8.8 +/- 2.7 ml; and on 100 micrograms of iodide plus 50 micrograms of levothyroxine, from 17.2 +/- 3.1 ml to 8.3 +/- 2.0 ml. When treatment was discontinued for three months, or the dosage reduced, thyroid volume increased again in the levothyroxine (to 11.3 +/- 2.5 ml) but not in the iodide group. Grey-scale values (by ultrasound, computer-aided estimation) after nine months were significantly different between the three treatment groups; no change was observed with levothyroxine, but after 150 micrograms of iodide as well as after combined treatment with levothyroxine and iodide there were marked decreases of grey-scale values; this is interpreted as reflecting a decrease in follicle size and colloid content of the thyroid which takes place after iodide supplementation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449042 TI - Combined treatment with growth hormone and gonadotropin-releasing hormone analogues in children with isolated growth hormone deficiency. AB - In subjects with an isolated GH deficiency the inhibition of puberty by GnRH analogue administration may be attempted to delay the onset, or to prolong the duration, of pubertal maturation in order to improve final height. We report our experience on the matter in 10 subjects (6M, 4F) suffering from isolated GH deficiency with a chronological age ranging from 6.5 to 10.6 years at diagnosis. After a period of 1-5.1 years of GH treatment, GnRH-analogues (long-acting D-Trp 6-GnRH) were added to GH for 12 months, when six subjects were still prepubertal and four in early puberty. During combined therapy, a regression in pubertal development was shown in three out of four children in early puberty, while serum testosterone or estradiol decreased. Height velocity decreased (from 5.23 +/- 1.49 (mean +/- SD) to 4.12 +/- 0.67 cm/year; p < 0.02), whereas height SD scores for bone age increased (from -0.75 +/- 0.42 to -0.47 +/- 0.55; p < 0.02). During the year of combined therapy, bone age increased only 0.57 +/- 0.27 years. The values for predicted height (TW2 and Bayley-Pinneau method) after combined treatment were also higher than those after treatment with GH alone (p < 0.02 and p < 0.001, respectively). Our preliminary data showed that the addition of GnRH analogues to GH in subjects with isolated GH deficiency reduces the effect of GH on height velocity, but determines an improvement in statural prognosis, although a proper answer will not be obtained until final height has been achieved. PMID- 1449043 TI - Serum levels of intact parathyroid hormone and alkaline phosphatase correlate with cortical and trabecular bone loss in primary hyperparathyroidism. AB - We examined the relationship between bone loss and several biochemical indices in 38 patients with primary hyperparathyroidism. Bone mineral density was reduced by 12 +/- 4.0% in the lumbar spine, 18 +/- 4.2% at the distal radius and 21 +/- 2.8% at the proximal radius (mean +/- SEM). There were significant negative correlations between the serum concentrations of intact parathyroid hormone (PTH) and the Z-scores of the bone mineral content at the proximal and distal radius. In the lumbar spine, bone mineral density was greater in patients with mildly elevated PTH and less in patients whose PTH levels exceeded 8.6 pmol/l. We also observed a strong association between increased levels of serum alkaline phosphatase and low bone mineral Z-scores. Our data thus indicate that cortical and, with the exception of mild primary hyperparathyroidism, trabecular bone loss is proportional to the concentration of circulating PTH and the severity of PTH induced bone turnover. For the individual patient, however, the usefulness of intact PTH and alkaline phosphatase measurements for assessing bone loss associated with primary hyperparathyroidism seems to be only limited. PMID- 1449044 TI - Effects of short-term growth hormone treatment on PTH, calcitriol, thyroid hormones, insulin and glucagon. AB - We measured changes in serum insulin-like growth factor-1 (IGF-1), calcitriol, parathyroid hormone (PTH), thyroid hormones, insulin, and plasma glucagon in response to seven days of treatment with a pharmacological dosage of recombinant human growth hormone (r-hGH) (0.1 IU/kg sc twice daily) or placebo in 20 normal male volunteers to evaluate whether the effect of r-hGH on biochemical bone markers could be attributed to changes in these hormones. Serum IGF-1 (p < 0.001) and vitamin D-binding protein (p < 0.001) increased steadily during treatment returning to baseline at day 14. Total calcitriol (p < 0.01) and free calcitriol index (p < 0.001) increased transiently at day 4. Furthermore, serum insulin (p < 0.001) and both total (p < 0.001) and free triiodothyronine (p < 0.02) increased during treatment, while serum PTH and plasma glucagon remained unchanged. In conclusion, pharmacological doses of r-hGH increased not only IGF-1 but also free calcitriol index, insulin, and free T3. The increase in these hormones may be co responsible for some of the observed effects of r-hGH on bone turnover and calcium homeostasis. PMID- 1449045 TI - Growth hormone stimulates galactopoiesis in healthy lactating women. AB - Sixteen normally lactating women underwent a double-blind randomized placebo controlled trial of recombinant human growth hormone (hGH) to assess the effect of hGH on milk production in early lactation. Milk volumes were measured by test weighing procedures of the infants and removal of residual milk on a control day and after 7 days of treatment with recombinant hGH (0.1 IU.kg-1 body weight.d-1) or placebo treatment. Although all women were lactating normally before the study commenced, milk volume in 8 hGH treated mothers was increased (p < 0.02) by 18.5 +/- 1.4% (mean +/- SEM) compared to 11.6 +/- 2.0% in the placebo-treated group (N = 8). No adverse effects were seen with hGH treatment and no major changes noted in milk constituents. The hGH concentrations in milk were low and did not change with therapy. Plasma concentrations of IGF-1 increased significantly within 24 h of hGH treatment and increased further towards the end of the trial to values of 2.6-fold above the pretreatment values. The concentration of IGF-1 in milk was approximately 100-fold lower than those observed in plasma and could only be reliably measured after size exclusion chromatography to remove the interfering influence of IGF binding proteins in the radioimmunoassay. All women treated with hGH showed a small increase in milk IGF-1 concentrations but the values remained within the range of values observed in women receiving the placebo treatment (1.2 4.4 micrograms/l). Growth hormone treatment increased milk volume in normal lactating women during early lactation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449046 TI - Effects of prolonged Acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin dependent diabetes mellitus. AB - The effect of prolonged treatment with Acipimox on in vivo peripheral insulin sensitivity, and on glucose and lipid metabolism, was investigated in patients with NIDDM in a double-blind study. Twelve NIDDM patients were randomized to treatment with either placebo or Acipimox in pharmacological doses (250 mg x 3) for three months. Fasting plasma glucose, insulin, C-peptide and HbA1c concentrations were unaffected after three months of acipimox treatment. However, fasting plasma non-esterified fatty acid (NEFA) concentrations were twofold elevated after Acipimox treatment (1.34 +/- 0.09 vs 0.66 +/- 0.09 mmol/l; p < 0.05). Despite this, repeated acute Acipimox administration after the three months' treatment period enhanced total insulin-stimulated glucose disposal to the same extent as acute Acipimox administration before the treatment period (367 +/- 59 vs 392 +/- 66 mg.m-2.min-1, NS; both p < 0.05 vs placebo glucose disposal) (267 +/- 44 mg.m-2.min-1). In conclusion, insulin resistance or tachyphylaxis towards the effects of Acipimox on insulin stimulated glucose disposal was not induced during prolonged Acipimox treatment. The lack of improvement of blood glucose control in the patients with NIDDM may be due to the demonstrated rebound effect of lipolysis. PMID- 1449047 TI - Effect of melatonin on the in vitro secretion of progesterone and estradiol 17 beta by ovine granulosa cells. AB - This study was undertaken to determine the effect of melatonin on steroid hormone production by ovine granulosa and luteal cells in vitro. Granulosa and luteal cells from ovine ovaries were cultured for nine days either in D-MEM only or in the presence of melatonin (0.86, 8.6, 86 nmol/l), ovine luteinizing hormone (oLH, 2 micrograms/l) or a combination of both these hormones. Progesterone (P4) and estradiol 17 beta (E2) were determined by validated RIAs. Melatonin stimulation began at either day 1 or day 5 of culture. Melatonin (0.86 nmol/l) significantly increased (p < 0.001) progesterone secretion by granulosa cells both when administered alone and when administered in combination with oLH; the more marked response was observed in the latter case. When the stimulation began at day 5, at a more advanced degree of differentiation of the cells, higher levels of P4 were observed. Higher concentrations of melatonin did not further increase progesterone production. Melatonin alone did not have a significant effect on the production of estradiol 17 beta; neither did melatonin stimulate progesterone production in either long-term cultured luteal cells or in short-term (1-2 h) cultured luteal and granulosa cells. The results of this study document a direct effect of melatonin in stimulating granulosa cells to produce progesterone, a synergistic activity between melatonin and luteinizing hormone and a different ability of granulosa cells to secrete P4 depending on the degree of differentiation. PMID- 1449048 TI - Diaphragmatic movement using ultrasound during spontaneous and mechanical ventilation: effect of tidal volume. AB - Using ultrasound (US) the effect of various tidal volumes on the movement of ventral, dome and dorsal parts of the right hemidiaphragm was studied, both during spontaneous and mechanical ventilation. Six healthy non-medicated volunteers who were in the supine position breathed spontaneously shallowly (tidal volume (VT) being 400 ml) (SB), and deeply (VT 1000 ml) (SB-deep). In addition, they were mechanically ventilated with intermittent positive pressure ventilation at three different VT's: 500 ml (IPPV-500), 1000 ml (IPPV-1000) and 1700 ml (IPPV-1700). The maximal movement was recorded in the ventral part in 2 volunteers during SB, in 3 during SB-deep, and in 3 and 5 subjects during IPPV 500 and IPPV-1700, respectively. The movement in dome was 100% during SB (all others standardized to this), 303 +/- 107% during SB-deep, 82 +/- 30% during IPPV 500, 165 +/- 70% during IPPV-1000 and 266 +/- 153% during IPPV-1700. An increased tidal volume is associated with an increase in the diaphragmatic movement studied by US. However, a larger VT is needed during mechanical ventilation to achieve the same amount of change as occurred with deep spontaneous breathing. PMID- 1449049 TI - Behavioural changes in children following minor surgery--is premedication beneficial? AB - One hundred and twenty-three male children, aged one to ten years, were studied to determine the influence of premedication on changes in patterns of behaviour following hospitalization for repair of inguinal hernias. Four comparable groups were selected for premedication regimen: (1) A control group without premedication; (2) oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg and droperidol 0.15 mg/kg; (3) oral midazolam 0.45 mg/kg; (4) intramuscular midazolam 0.15 mg/kg. Standard inhalational anesthesia was used and caudal blocks employed for analgesia. The parents returned a questionnaire at two weeks. Changes in behaviour were reported in 78% of the children and overall, premedication showed little benefit. However, midazolam premedication was associated with a significantly lower incidence of night-time crying and awakening, compared with no premedication. Only for night-time crying and day-time toilet training did age below five years prove to be a significant contributing factor. PMID- 1449050 TI - Aging and immunity. AB - The function of the immune system peaks at around puberty and gradually declines thereafter with advance in age. The age-related decline of immunological function primarily occurs in the T cell-dependent immune system and is generally associated with increase in susceptibility to infections as well as in incidence of autoimmune phenomena in the elderly. The age-related change in T cell dependent immune functions can be ascribed to the physiological thymic atrophy which starts in an early stage of life. Emigration of T cells from the thymus to the periphery mainly takes place in the late fetal and newborn stage, and dramatically declines after puberty. In other words, the thymic capacity to promote T cell differentiation starts to change in the early stage of life in terms of quantity and quality of T cells. Thus, the composition of T cell-subsets in the periphery gradually changes with age, resulting in the alteration of T cell functions in the elderly. The restoration of immunological functions of the aged individuals is possible and might be beneficial for them to cope with various diseases associated with aging. Physiological thymic atrophy is controlled by both extrathymic and intrathymic factors, and is not a totally irreversible process. The process of thymic atrophy might be explained by further understanding of the relationship between the neuroendocrine and the immune systems. PMID- 1449051 TI - Effects of alkyl alcohols and related chemicals on rat liver structure and function. III. Physiochemical properties of ethanol-, propanol- and butanol- treated rat liver mitochondrial membranes. AB - The physicochemical properties of mitochondria in liver tissue obtained from rats given 32% ethanol, 32% propanol or 6.9% butanol in drinking water for up to 3 months were investigated using differential scanning calorimetry and fluorescence polarization measurements. The results obtained were as follows: 1) Phospholipids extracted from mitochondria showed increases in the relative amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylserine, and a decrease in the relative amount of phosphatidylethanolamine. An increase in the unsaturated/saturated fatty acid ratio of phospholipids was also observed. 2) Elevation of the thermotropic lipid phase transition temperature with a decrease in the enthalpy value (delta H) was revealed by differential scanning calorimetry. 3) The elevation of the lipid phase transition temperature was detected also by fluorescence polarization measurements using 1,6-diphenyl-1,3,5 hexatriene (DPH) as a probe. Elevation of mitochondrial membrane fluidity was found in some of the experimental animals, but most showed no changes in comparison with the control. A possible role of membrane fusion in the mechanism of formation of ethanol-, propanol- and butanol-induced hepatic megamitochondria is discussed on the basis of these results. PMID- 1449052 TI - Immunohistochemical localization of gangliosides in ENU-induced rat glioma. AB - Biochemical studies have indicated that the structurally simple gangliosides, including GD3 and GM3, are major glycolipid components of glioma tissues. In order to clarify the localization of the gangliosides in ethylnitrosourea-induced rat glioma, an immunohistochemical study was performed using antibodies against GM1, GM3, and GD3. The results obtained in normal fetus, newborn, and adult rat brain, and also in human glioma, were compared. In fetal and newborn rat brain, GD3 was present mainly in the neuroepithelial cell surface of the matrix and subependymal layers of the ventricular wall, but GM3 and GM1 were not detected. In adult rat brain, GD3-positive cells were absent, or present in diminished number, and GM1 was found chiefly in the neuropil of the cerebral cortex. Most of the rat glioma cells were positive for GD3, but not for GM1. It was demonstrated that the ganglioside composition of glioma cells was similar to that of immature neuroectodermal cells in fetal and newborn rat brain. Furthermore, the number of GD3-positive oligodendroglioma cells increased with tumor growth. In anaplastic gliomas and gross oligodendrogliomas, most tumor cells expressed not only GD3 but also GM3. These results suggest that GD3 is a marker of proliferating neuroectodermal cells, and that activity of the key enzymes in ganglioside synthesis alters with tumor growth and anaplastic change. PMID- 1449053 TI - Incidence of Paneth cells in minute tubular adenomas and adenocarcinomas of the large bowel. AB - This study attempted to demonstrate the incidence of Paneth cells within large bowel tubular adenoma and adenocarcinoma according to location and macroscopic appearance using minute tumors (up to 5 mm in size). We have shown that Paneth cells were sometimes seen in the early stage of the development of large bowel epithelial neoplasia. According to the macroscopic appearance (elevated or depressed type), in large bowel epithelial neoplasia, there was a statistical difference between the depressed type (32.5%, 14 of 40 cases) and the elevated type (16.6%, 24 of 145 cases) (Chi square analysis, p < 0.05) in the incidence of Paneth cells. Paneth cells were seen more frequently in adenocarcinoma (45.8%, 11 of 24 cases) than in tubular adenoma (16.8%, 27 of 161 cases), with a significant statistical difference (Chi square analysis, p < 0.01). According to location, in both tubular adenoma and adenocarcinoma, Paneth cells were more frequently observed in the proximal colon (tubular adenoma: p < 0.01, adenocarcinoma: p < 0.05, Chi square analysis). PMID- 1449054 TI - Three human osteosarcoma cell lines exhibiting different phenotypic expressions. AB - to elucidate the differences in histological features and biological behavior of osteosarcomas, three human osteoblastic-type osteosarcomas were studied in vitro and in nude mice. The secretory processing and extracellular fiber formation of type I collagen proved to be the most important factor in bone formation in the osteosarcomas. Alkaline phosphatase also seemed to be important. However, we were unable to find any particular protooncogene abnormalities which could have been implicated in the occurrence or biological behavior of these osteosarcomas. PMID- 1449055 TI - An autopsy case of Kawasaki disease with reference to occurrence of acute coronary thrombosis in the convalescent stage. AB - A one-year, four month-old boy who had suffered from Kawasaki disease died suddenly during convalescence despite intensive gamma-globulin treatment. Autopsy revealed a) sausage-like aneurysms of the left and right coronary arteries and fresh thrombosis in the right coronary aneurysm, b) fresh transmural myocardial necrosis in the whole wall of the left ventricle and the anterior part of the wall of the right ventricle, and c) swelling of the cervical lymph nodes and thymus (60 g). Histologically, fibrocellular thickening of the intima and destruction of the media and internal elastic lamina were conspicuous in the area of the aneurysm, but those of the intima and media in the areas adjacent to the aneurysm were mild. Abrupt narrowing of the lumen at the border between the aneurysm and periphery of the right coronary artery was detected, and this may have been responsible for formation of the thrombus in the right coronary aneurysm. In the systemic arteries, perivascular fibrosis was very noticeable despite less severe injury to the intima and media. These findings suggest that severe inflammation of the periarterial regions was present in the acute phase. The lymph system still showed inflammation, supporting the infectious or toxic nature of Kawasaki disease. PMID- 1449056 TI - Carcinoid tumor of the middle ear containing serotonin and multiple peptide hormones. A case report and review of the pathology literature. AB - A 69-year-old man complaining of longstanding hearing loss and mild otorrhea was found to have a mass obliterating the external auditory canal and polypous tympanic mucosa with accompanying absence of the tympanic membrane and ossicular chain. Tumors excised from the external auditory canal and tympanum showed histologic features essentially characteristic of a carcinoid tumor: a ribbon or festoon arrangement of tumor cells, formation of anastomosing cords and glandular spaces, presence of numerous argyrophilic as well as argentaffin secretory granules within many of the tumor cells, and ultrastructural evidence of neurosecretory granules in the tumor cell cytoplasm. Immunohistochemically, the tumor was found to contain not only neuronal marker substances such as neuron specific enolase, S-100 protein and chromogranin A, but also serotonin and multiple peptide hormones such as pancreatic polypeptide, glucagon, cholecystokinin and leucine-enkephalin. A review of the pathology of 17 previous cases of carcinoid of the middle ear suggested that this type of carcinoid may have a variegated hormone profile among carcinoids of foregut origin, and hormonally may resemble ileal carcinoid arising from the midgut, although their histogenetic origins may differ, because of frequent production of serotonin. PMID- 1449057 TI - Catalytic site in the beta subunit of H(+)-ATPase from Escherichia coli:the glycine-rich sequence and its interaction with Ser-174. PMID- 1449058 TI - Structure and function of proton-translocating nicotinamide nucleotide transhydrogenase. PMID- 1449059 TI - The regulatory domain of fungal and plant plasma membrane H(+)-ATPase. AB - The activity of fungal and plant plasma membrane H(+)-ATPases seems to be regulated by modulation of the interaction of an inhibitory domain at the C terminus with the active site. In the yeast ATPase, a mutation at the active site (Ala547- > Val) and a deletion of the C-terminus result in constitutive activation. A double Ser911- > Ala, Thr912- > Ala mutation at the C-terminus (defining putative phosphorylation sites) locks the enzyme in the inhibited state and can be suppressed by the Ala547- > Val mutation at the active site. This provides genetic evidence for domain interaction. In plant ATPase, proteolytic removal of the C-terminus also results in constitutive activation. A peptide covering a region of the plant C-terminus with homology to the yeast C-terminus inhibits the truncated plant ATPase. This suggests similar regulatory mechanisms in fungal and plant ATPases. PMID- 1449060 TI - Molecular correlates of physiological regulation in a P-type H(+)-ATPase. PMID- 1449061 TI - Site-directed mutagenesis of the Ca2+ ATPase of sarcoplasmic reticulum. AB - We have cloned cDNA encoding the Ca2+ ATPase from fast-twitch skeletal muscle and, on the basis of its amino acid sequence and immunological studies of its topology, have made deductions concerning its secondary structure and active sites. These deductions have led us to test models for Ca2+ transport through expression of the protein in functional form in COS-1 cells, mutagenesis, and measurement of altered function. Mutation of about 250 of the 1000 amino acids making up the Ca2+ pump has indicated that the sites of high affinity Ca2+ binding are located in the center of the transmembrane domain and are made up from residues located in transmembrane sequences M4, M5, M6 and M8. The ATP binding site appears to be located in the headpiece and is made up from a series of loop sequences connecting alternating alpha helices and beta strands. Sites of conformational interaction appear in all domains throughout the Ca2+ pump. In our present model, Ca2+ transport occurs through binding to high affinity sites accessible to the cytoplasm in the E1 conformation, followed by release to the lumen from low affinity sites which form during the ATP-induced transition of the protein from the E1 to the E2 conformation. PMID- 1449062 TI - Structural basis for the E1/E1P-E2/E2P conformation changes in the sarcoplasmic reticulum Ca(2+)-ATPase studied by site-specific mutagenesis. AB - Site-specific mutagenesis and functional expression of cloned cDNA of the sarcoplasmic reticulum Ca(2+)-ATPase have been used to demonstrate that exchange of single amino acid residues in the Ca(2+)-ATPase can lead to forms with either "E1/E1P" or "E2/E2P" characteristics. The localization of the mutated residues identifies the M4S4 segment of the ATPase molecule as central to the energy tranducing conformation change, and on the basis of this information a model for the pump mechanism is discussed. PMID- 1449063 TI - Genetic probing of the yeast plasma membrane H(+)-ATPase. AB - The H(+)-ATPase from Saccharomyces cerevisiae has been probed by a random genetic approach that has led to the isolation of primary and secondary site mutations. These H(+)-ATPase (PMA1) mutants help define specific functional, as well as interacting, regions of the H(+)-ATPase. Cellular resistance to hygromycin B has been an important selection tool for the isolation of pmal mutants. One prominent hygromycin B-resistant mutant, pmal-105, was found to have a S368F mutation near the site of phosphorylation (D378) in the catalytic core. This mutation prevents growth in low pH or NH(4+)-containing medium and induces an acid-sensitive Vmax for ATP hydrolysis, as well as a pronounced insensitivity to vanadate. The prominent cellular and biochemical phenotypes of this strain facilitated a detailed revertant analysis to identify protein structure domains that interact directly or indirectly with the localized region defined by the F368 mutation. Partial revertants were isolated which were resistant to low pH or NH4+ but retained hygromycin resistance. Second site mutations were found within the first and second cytoplasmic loop domains, as well as in transmembrane segments 1-3 & 7. All of the revertant enzymes have a stable Vmax but some show changes in the pH optimum for ATP hydrolysis; all display vanadate sensitivities ranging between the insensitive F368 mutant and the fully-sensitive wild type enzyme. Revertant analyses have also been performed on two other pma1 mutants which carry the mutations A135V and G158D in transmembrane segments 1 and 2, respectively. Compensating second site mutations to these mutations were identified in transmembrane segments 1, 2, 4 & 7, as well as within the central catalytic domain. These analyses have helped identify interacting protein structure domains that may participate in coupling ATP hydrolysis to proton transport. Furthermore, they facilitate the construction of structural models to account for these interactions. PMID- 1449064 TI - Kdp, a bacterial P-type ATPase whose expression and activity are regulated by turgor pressure. AB - The Kdp ATPase is a P-type ATPase consisting of three large protein subunits in a complex that probably contains 2 copies of each subunit. A small hydrophobic peptide, encoded in the same operon as the large subunits, may also participate. Kdp has very high affinity for K+ and serves to scavenge this ion when its concentration is low. Kdp responds to turgor pressure at two levels, at the level of activity and of expression. Kdp mediates net uptake when turgor is low, but mediates exchange without net change when turgor is normal. Kdp is expressed only when turgor is low. This control is mediated by a pair of regulatory proteins, members of the class of 'sensor-effector' regulators widely distributed in bacteria. It is suggested that low turgor changes the conformation of the KdpD 'sensor' protein, activating its presumed kinase activity to phosphorylate KdpE, the 'effector' protein, and phospho-KdpE in turn turns on expression of the operon that encodes the Kdp complex. PMID- 1449065 TI - The Na+/glucose cotransporter (SGLT1). AB - An important class of Na+ transport proteins is the cotransporters. They exist in bacteria and animal cells and are responsible for the "active" accumulation of sugars, amino acids, carboxylic acids and some ions, e.g., I-, Cl-, and PO-4, in cells. In the small intestine and renal proximal tubule the cotransporters play an important role in the transport of salt and water across the epithelia. The most well known and best characterized Na+ cotransporter is the intestinal brush border Na+/glucose cotransporter. We have cloned, sequenced, and expressed both the rabbit and human Na+/glucose cotransporters. The cDNAs code for 73kDa proteins with 662-664 residues (86% identity). Secondary structure analysis suggests a 12 membrane-spanning helical model with the N- and C-termini in the cytoplasm. A single N-linked glycosylation site is utilized at Asn248. These sugars are not required for function. Two essential residues for functional expression in oocytes have been identified, Asp28 and Arg300. In two sisters with glucose-galactose malabsorption the transport defect is caused by a missense mutation changing Asp28 to Asn28, and we have found that changing Arg300 to Cys300 eliminated transport. Current research is directed to finding residues and domains essential for ligand binding and transport, and we are using electrophysiological techniques to correlate structure and function. PMID- 1449067 TI - Numerical simulation of uni-site and bi-site ATP-hydrolysis catalyzed by the membrane-bound H(+)-ATPase from chloroplasts. AB - The kinetics of ATP-hydrolysis catalyzed by the H(+)-ATPase from chloroplasts was described by an enzyme kinetic model where either one (uni-site catalysis) or two (bi-site catalysis) sites are operating. Numerical simulations are carried out with the software package LARKIN using measured rate constants as a basis. When the ATP-concentration is increased up to 20 nM (at 20 nM enzyme concentration) a change from uni-site to bi-site catalysis occurs at about 7 nM. The measured effective rate constants change by a factor two. However, the calculated rate constants for the second site are drastically increased. PMID- 1449066 TI - Regulation of the (Ca(2+)+Mg2+)-ATPase of basolateral membranes from kidney proximal tubules by kinase-mediated phosphorylation and by insulin. AB - Membrane vesicles derived from the basolateral aspect of kidney proximal tubule cells are phosphorylated by ATP in the absence of Ca2+. This Mg(2+)-dependent, hydroxylamine-resistant phosphorylation was associated with a 50% inhibition of the (Ca(2+)+Mg2+)-ATPase activity measured upon addition of micromolar Ca2+ concentrations, enough to saturate the high-affinity sites of the Ca2+ pump. The presence of either the protein kinase inhibitor H7 or insulin during phosphorylation virtually eliminated the inhibitory effect associated with phosphorylation. However, insulin itself inhibited ATP hydrolysis by the (Ca(2+)+Mg2+)-ATPase when it was present in the assay medium containing buffer, ATP, Mg2+ and Ca2+, the hydrolytic activity being initiated by addition of the membranes without prior phosphorylation. These results suggest that insulin may play a role in regulating transepithelial Ca2+ transport in renal proximal tubules, and that its effects may be linked with a kinase-mediated process that depends on the functional state of the (Ca(2+)+Mg2+)-ATPase. PMID- 1449068 TI - Reaction cycle and thermodynamics in bacteriorhodopsin. AB - Light causes the all-trans to 13-cis isomerization of the retinal in bacteriorhodopsin; the thermal relaxation leading back to the initial state drives proton transport first via proton transfer between the retinal Schiff base and D85 and then between the Schiff base and D96. The reaction sequence and thermodynamics of this photocycle are described by measuring time-resolved absorption changes with a gated multichannel analyzer between 100 ns and 100 ms, at six temperatures between 5 degrees C and 30 degrees C. Analysis of the energetics of the chromophore reaction sequence is on the basis of a recently proposed model (Varo & Lanyi, Biochemistry 30, 5016-5022, 1991) which consists of a single cycle and many reversible reactions: BR -hv-->K<==>L<==>M1- >M2<==>N<==>O-->BR. The existence of the M1-->M2 reaction, which functions as the switch in the proton transfer, is confirmed by spectroscopic evidence. The calculated thermodynamic parameters indicate that the exchange of free energy between the protein and the protons is at the switch step. Further, a large entropy decrease at this reaction suggests a protein conformation change which will conserve delta G for driving the completion of the reaction cycle. The results provide insights to mechanism and energy coupling in this system, with possible relevance to the general question of how ion pumps function. PMID- 1449069 TI - Characterization of proton transport in bone-derived membrane vesicles. AB - ATP-dependent proton transport was characterized in membrane vesicles, prepared by differential centrifugation from medullary bone of egg laying hens, a source rich in osteoclasts. The H(+)-ATPase present in this preparation showed the characteristics of a vacuolar H(+)-ATPase in its sensitivity to inhibitors, including bafilomycin A1, its sensitivity to cold treatment and its electrogenic mechanism. There was no evidence for a direct activation of the H(+)-ATPase by anions, including Cl-. These results are consistent with the view that the osteoclast, the cell responsible for bone resorption, secrets acid by means of a vacuolar H(+)-ATPase. PMID- 1449070 TI - A novel type haem group of cytochrome o from Escherichia coli. AB - The b-type haem groups of cytochrome o have generally been thought to be protohaems. However, we have recently shown that they are of a novel kind, for which we propose the name haem O. On the basis of its pyridine haemochrome spectrum, chromatographic behaviour and molecular mass of 839 Da, we suggest that haem O is a haem A-like molecule with the formyl group in position 8 of the latter replaced by methyl, but with retention of the 17-carbon hydroxyethyl farnesyl side chain in position 2, characteristic of haem A. This structure has now been unambiguously verified by resonance Raman, 1H-NMR, and infrared spectroscopy, as well as by mass spectroscopy of molecular fragments, in collaboration with C. K. Chang, G. T. Babcock and their co-workers at Michigan State University. Properties of haem O are compared with haem A and protohaem, and possible contributions of haem O structure to the cytochrome o oxidase function are discussed. PMID- 1449071 TI - Expression of subunit II of chloroplast H(+)-ATPase in an Escherichia coli mutant lacking subunit b of its H(+)-ATPase. AB - The DNA of subunit II of the H(+)-ATPase from spinach chloroplast was expressed in Escherichia coli. It was found that a high gene dose is lethal to E. coli. With a lower gene dose subunit II was not able to substitute for the homologous subunit b in the E. coli ATP synthase. PMID- 1449072 TI - Mutational analysis of the role of Lys684 in the Ca(2+)-ATPase of sarcoplasmic reticulum. AB - Site-specific mutagenesis of the sarcoplasmic reticulum Ca(2+)-ATPase was used to investigate the functional role of Lys684 located in the "hinge-domain", a highly conserved region of the cation-transporting ATPases. Mutation of Lys684 to Arg, Ala, His and Gln resulted in complete loss of calcium transport function and ATPase activity. For the Lys684- > Ala, His, Gln mutants, this coincided with a loss of the ability to form a phosphorylated intermediate from ATP or Pi, whereas the Lys684- > Arg mutant retained the ability to phosphorylate from ATP with normal apparent affinity, demonstrating the importance of the positive charge. On the other hand, no phosphorylation was observed with Pi as substrate in this mutant. Examination of the partial reactions following phosphorylation from ATP in the Lys684- > Arg mutant demonstrated a reduction of the rate of transformation of the ADP-sensitive phosphoenzyme intermediate (E1P) to the ADP insensitive phosphoenzyme intermediate (E2P), which could account for the loss of transport function. Once accumulated, the E2P intermediate was able to decompose rapidly in the presence of K+ at neutral pH. In the Lys684- > Ala mutant, nucleotides were found to protect with normal affinity against intramolecular cross-linking induced with glutaraldehyde, indicating that the nucleotide binding site was intact. These data point to a role of Lys684 in the binding and transfer of phosphate to the protein, and in the transport-associated conformational changes of the phosphorylation site. PMID- 1449073 TI - An atomic model for the structure of bacteriorhodopsin, a seven-helix membrane protein. AB - A three-dimensional map of bacteriorhodopsin has been obtained, at near-atomic resolution, by collecting and analysing electron diffraction patterns and electron micrographs from crystals of bacteriorhodopsin preserved at very low temperatures. The map shows a resolution of 3.5 degrees in a direction parallel to the plane of the membrane, but poorer resolution perpendicular. It shows many features well resolved from the main density of the seven alpha-helices, which we interpret as the bulky sidechains of tyrosine, phenylalanine and tryptophan, as well as a very dense feature, which is the beta-ionone ring of the retinal chromophore. Using these bulky side chains as starting points and taking account of bulges of density for the smaller side chains such as leucine, we built an atomic model for the residues between 8 and 225. There are 21 amino acids from all 7 helices surrounding the retinal and 26 amino acids contributed by 5 helices that form the proton channel. Ten of the amino acids in the middle of the proton channel are also part of the retinal-binding site. The model provides a useful basis for considering the mechanism of proton pumping and in the interpretation of other experimental data. In particular, the model suggests that the pK changes in the Schiff base must act as the means by which light energy is converted to proton pumping through the channel. Asp-96 is on the pathway from the cytoplasm to the Schiff base and asp-85 on the pathway from the Schiff base to the extracellular surface. The experimental map and the building of the model of the structure will be described, as well as our interpretation of the structural basis of the mechanism. PMID- 1449074 TI - Purification of the H(+)-ATPase from chloroplasts. AB - Triton X-100* was replaced in the purification of the H(+)-ATPase from chloroplasts by either octyl glucoside, octyl thio glucoside or the zwitterionic detergent CHAPS. The results indicate that the enzyme can be purified without Triton X-100 and retain full activity. PMID- 1449075 TI - Structure and function of the Na(+)-translocating ATPase of Propionigenium modestum. AB - The strict anaerobic bacterium Propionigenium modestum performs a Na+ cycle over the membrane to couple ATP synthesis to the decarboxylation of methyl-malonyl CoA. The responsible ATPase has a typical F1F0 structure, the water-soluble F1 moiety being composed of five different subunits and the more firmly membrane bound F0 part consisting of three different subunits. The F1F0 ATPase but not F1 alone was specifically activated by Na+ ions, suggesting that the Na+ binding site is located on the F0 moiety. The ATPase reconstituted into proteoliposomes catalyzed an ATP-dependent Na+ accumulation that was stimulated to the same extent by dissipating the membrane potential with valinomycin or with the uncoupler carbonylcyanide-m-chloro phenylhydrazone. The transport of Na+ is therefore a primary event, not a secondary event involving the intermediate formation of a proton gradient. The ATPase also catalyzed H+ translocation at Na+ concentrations below 1 mM. Our results indicate a common mechanism of the ATPase for Na+ and H+ (H3O+) translocation and a switch from H+ to Na+ translocation by increasing the Na+ concentration. A hybrid ATPase consisting of F1 from E. coli and F0 from P. modestum had the same specificity with respect to the translocated cations as the homologous F1F0 ATPase of P. modestum, indicating again that the Na+ (H+) binding site is located on the F0 part. Also in accord with this supposition is a diffusion potential-induced translocation of Na+ or H+ through the F0 part of the enzyme complex. The phylogenetic relationship between the Na(+)-translocating ATPase of P. modestum and other F1F0 ATPases has been clearly demonstrated by sequencing studies. PMID- 1449076 TI - Pancreatic islet cell regeneration and growth. Introduction. PMID- 1449077 TI - The partial isolation and characterization of ilotropin, a novel islet-specific growth factor. AB - In this series of studies, we have presented evidence for a novel, pancreatic islet-specific growth factor, which we call ilotropin. Ilotropin is acid stable, heat stable, ethanol-precipitable, and sensitive to trypsin digestion. It appears to have a molecular weight between 29 - 44,000, and preliminary data not presented here suggests that it has a relatively basic pI. Unlike many other growth factors, ilotropin does not bind to heparin. Ilotropin is distinguishable from most of the known growth factors on the basis of at least one of the characteristics established in these studies. The apparent molecular weight of 29 - 44,000 eliminates all but the larger growth factors such as PDGF and hepatic growth factor. The fact that ilotropin is acid stable rules out identity with hepatic growth factor, and its lack of binding to heparin and apparent basic pI rules out identity with PDGF. Thus, the combination of characteristics described in these studies eliminates most of the known growth factors as candidates for the role of ilotropin. Certain growth factor precursor molecules (e.g. TGF-a) and several interleukins and cytokines (e.g. pro-IL-1 and melanocyte growth factor) also fall into this molecular weight range. Whether these proteins might be related to ilotropin or play a role in its biological activity remains to be determined. Current studies of ilotropin include further purification to homogeneity, determination of the peptide sequence of ilotropin, and development of an in vitro bioassay using trophic responses of primary cultures of pancreatic duct cells as an indicator of ilotropin activity. With purified material we ought to be able to identify the cells of origin and the target cells for the action of ilotropin, and establish assays to determine the relationship to failure of beta cell regeneration that accompanies diabetes. Ultimately we hope that ilotropin may lead to new ways of approaching aspects of the problems presented in pancreatic beta-cell failure. PMID- 1449078 TI - The physiological stop pathway: target regulation of axonal growth. PMID- 1449079 TI - Calcium regulation of myosin I--a motor for membrane movement. PMID- 1449080 TI - Amylin expression in the pancreatic beta-cell. PMID- 1449081 TI - Studies of composite grafts of fetal pancreas (FP) and fetal liver (FL) in the streptozotocin-induced diabetic rat. AB - A hepatotrophic effect of pancreatic islets on co-transplanted hepatocytes has been described recently by Ricordi et al. We investigated a possible reciprocal effect of co-transplanted fetal liver (FL) on fetal pancreas (FP) isografted into streptozotocin diabetic rats. FL was co-transplanted with FP in three sites: the new intramural small bowel (ISB) site, the conventional renal subcapsular (RSC) site, and the historically inhospitable intramuscular (IM) site. Overall, as compared to grafts of FP alone, composite FP/FL grafts consistently provided earlier restoration of normoglycemia in streptozotocin diabetic recipients (24 +/ 8 vs. 67 +/- 43 days P = 0.001). The proportion of recipients rendered normoglycemic and the clearance of glucose was site-dependent. For FP and FP/FL recipients respectively, the ISB site resulted in 100% normoglycemia in both groups (19/19 and 6/6), the RSC site resulted in 71% (5/7) and 40% (2/5) and the IM site resulted in 14% (1/7) and 67% (6/9). In normoglycemic recipients, glucose clearance was normal or supraphysiologic except for the RSC site. Composite isografts brought about normoglycemia in 75% (6/8) of recipients treated with beta-cell toxic doses of cyclosporine that prevented reversal of diabetes in recipients of FP alone. Co-transplantation of FL benefits FP through paracrine mechanisms mediated by unknown factor(s). Thus, as compared to grafts of FP alone, composite FP/FL grafts established normoglycemia more rapidly, mitigated cyclosporine toxicity and corrected diabetes when transplanted in the small bowel site. There are several mediators that may be responsible for these paracrine effects between the liver cells and the pancreas. IGF-1 elaborated by FL is the most likely trophic factor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449082 TI - The effects of IGF-I and IGF-II on cell growth and differentiation in the central nervous system. AB - Both IGF-I and IGF-II peptides have been localized to specific brain regions. The distribution of IGF-I is homogeneous whereas IGF-II appears to be more local. Two species of IGF receptors are found in the CNS. The type II (m6P) is similar to that in the periphery, but the type I has nearly the same affinity for IGF-I and IGF-II. IGF-I has now been shown to provide cell growth and survival as well as stimulate neurite outgrowth. Dorsal root ganglia and sympathetic neurons are sensitive to IGF-II and the action may be additive with NGF. Cells other than neurites, such as oligodendrocytes respond to the IGFs as well as primary and transformed lines. The mechanism of action has not been resolved but IDG-II appears to act via G-protein coupled activation of protein kinase C. Interaction between various growth factors and the IGFs may be due to up or down-regulation of the receptor predicated by the non-homologous peptide. PMID- 1449083 TI - Islet beta-cell regeneration and reg genes. AB - In this paper, we show that the reg gene is expressed in experimentally induced regenerating or hyperplastic islets. We have previously reported that ectopic expression of the reg gene occurs in some human colonic and rectal tumors, suggesting that enhanced reg expression may be related to the proliferative state of tumor cells. Reg protein has also been shown to have significant sequence homology with plant and animal lectins, a class of compounds that has been shown to be a growth promoter. At present, any direct relationship between reg protein and beta-cell replication remains to be established. However, since the reg protein is a secretory protein and reg can be expressed at an early stage of pancreatic cell differentiation, the reg protein may act on the stem cells of beta-cells in an autocrine or paracrine manner. In normal mature exocrine cells, the reg gene is expressed and the gene product may be necessary to maintain adequate exocrine pancreatic function. The physiological reasons for the maintenance of two functional reg genes encoding proteins of slightly different sequence in mice are still unclear. The cloning of additional rat and human non allelic reg genes could provide additional clues. PMID- 1449084 TI - Factors regulating islet regeneration in the post-insulinoma NEDH rat. PMID- 1449085 TI - Regeneration of pancreatic endocrine cells in interferon-gamma transgenic mice. AB - We have shown that the pancreatic duct cells of IFN-gamma mouse are actively multiplying and that many duct cells differentiate to become endocrine cells. This islet regenerating process closely parallels the islet development during normal organogenesis in the fetus and offers a model for studying the cell lineage relationships of islet cells. The subject has received wide interest and intensive research in recent years. One of the noteworthy results of this study is the finding that duct cells retain the ability to proliferate and to differentiate into islet cells. Under normal conditions, duct cells do not continue to multiply or to differentiate. The results suggest that in the transgenic mice, the progenitor cells of embryonic multipotential duct cells transform into adult cells, but in the presence of appropriate signals or stimuli can resume their multipotential property. The appearance of hepatocytes indicates that while the cell proliferation observed largely results in endocrine cells, other differentiation pathways are occasionally possible. We also detect a few large cells containing albumin and alpha-fetoprotein in the periductal area. Pancreatic hepatocytes have also been observed in the rat after recovery from copper deficiency diet. Thus, the regeneration of islet cells in transgenic mice provides a model system for the study of factors modulating the growth pattern as well as the differentiation pathway. PMID- 1449086 TI - The role of growth hormone and prolactin in beta cell growth and regeneration. PMID- 1449087 TI - Trophic stimulation of the ductular-islet cell axis: a new approach to the treatment of diabetes. AB - We have established a model in which cellophane wrapping induces reiteration of the normal ontogeny of beta-cell differentiation from ductal tissue. The secretion of insulin is physiologic and coordinated to the needs of the animal. Streptozotocin-induced diabetes in hamsters can be "cured" at least 1/2 the time. There appears to be activation of growth factor(s) within the pancreas acting in an autocrine, paracrine or juxtacrine manner to induce ductal cell proliferation and differentiation into functioning beta-cells. Given the results of our studies to date, it does not seem premature to envisage new approaches to the treatment of diabetes mellitus. Identification of the factor(s) which regulate islet cell proliferation and differentiation in our model may permit islets to be grown in culture. This concept could be extended to induce endocrine cell differentiation in-vitro as well. Furthermore, islet cell growth factors could be used to provide "trophic support" to islet transplants as a means of maintaining graft viability. There may also be greater scope for gene therapy when the growth factor(s) has been isolated, purified, sequenced and cloned. PMID- 1449088 TI - [Peri-orbital surgical approaches]. AB - After having made a definitive diagnosis in patients with orbito-frontal pathology, the choice of incision is an important factor to achieve good intra operative exposure of the region, as well as to obtain a good functional and aesthetic result. In the majority of cases we prefer to utilize the incisions commonly used for blepharoplasty, especially the transconjunctival approach popularized by Tessier. Other more classic accesses such as the superolateral, infra-orbital and intra-oral incisions, are reserved for treatment of cases of orbitomalar (communition) fractures. We feel there are limited indications for use of incisions through the eyebrows with medial extensions for exposure of isolated lesions of the medial orbital wall, orbital roof, and the anterior wall of the frontal sinus. However they may become very useful as the primary incisions in the treatment of open fractures of the orbital region. The bicoronal incision, a classical approach in neurosurgery, is also being used by us in cases of tumors and complicated middle face fractures which appear to extend to the orbito-frontobasal region in 40% of our patients. In addition it provides excellent access for post-traumatic reconstruction of orbito-frontal bone defects and impacted fractures. A combination of different incisions: bicoronal, peri orbital and intra-oral, may be indicated for the correction of syndromal anomalies such as Treacher-Collins, for treatment of complicated facial fractures, or for pure aesthetic surgery procedures, such as the "mask-lift" introduced by Tessier. PMID- 1449089 TI - Gingival localization of fibrosarcoma of soft oral tissues: case report. AB - A gingival localization of fibrosarcoma of soft oral tissues was described in a 58-year-old female. Primary fibrosarcoma of the head and neck region is rare. The histological appearance of the tumour is related to its grade of differentiation. The amount of collagen is variable. The accepted treatment is radical surgery; but metastases occur frequently in the lungs. PMID- 1449090 TI - [Pedicled facial bone flap for closure of the approach in Caldwell-Luc type sinus operations. Its role in the prevention of postoperative complications]. AB - The primary or secondary reconstruction of the facial access after Caldwell-Luc and the more selective resection of sinusal mucous membranes can be important in the therapy and prevention of postoperative complications such as neuralgic facial pain, formation of cysts and chronic sinusitis. The different osteoplastic sinus operations are described and the use of a pedicled bonelid is illustrated. The most common accepted ethiology of post-operative pain is based on the formation of scar-tissue. Postoperative pain is first being treated conservatively, while in case of persisting pain an exploration with dissection of the infra-orbital nerve and reconstruction of the facial defect can be indicated. In a retrospective study of 36 patients the results of our surgical therapy are illustrated. PMID- 1449091 TI - [Complications of orbito-frontobasal fractures]. AB - Complications of fronto-basal trauma can, as a function of their severity, be divided into three classes: life-threatening situations, functional complications and cosmetic defects or facial deformities. They find their origin in the type of trauma, the extent of the lesions of bone and soft tissues, as well as in their timely management and quality of treatment. The etiology of the most common complications and their significance are covered with accent on inadequate primary treatment, insufficient repair of dural lesions, inadequate drainage, unstable osteosynthesis, insufficient treatment of scalp- and frontal defects, and finally the lack of antibiotic prophylaxis. The major complications of frontobasal trauma such as chronic cerebral spinal fluid fistulae and pneumocephalus are reviewed. Attention is also given to the importance of adequate drainage in cases of chronic ethmoidofrontal sinusitis, and on the treatment of osteomyelitis and sinus cysts. The therapeutic possibilities in patients with tissue deficits, i.e. reconstruction of frontal skull defects using autologous hip and rib material, as well as split calvarial bone grafts is discussed. PMID- 1449092 TI - Optimizing Antianginal Therapy: A Consensus Conference. Boca Raton, Florida, February 7-9, 1992. PMID- 1449093 TI - Mechanisms of myocardial ischemia. AB - Traditionally, myocardial ischemia has been viewed as an imbalance in the supply and demand of myocardial oxygen. Stable angina is usually considered to involve a fixed lesion, whereas unstable angina involves a fixed lesion as well as such components as platelet aggregation, thrombotic processes, and vasospasm. Variant angina involves primarily vasospasm. A newer concept holds that most angina results from mixed mechanisms in which both fixed lesions and vasomotor alterations play a role. These mechanisms are responsible for mixed ischemic events, characterized by episodes at varying levels of exertion, with or without anginal pain. This concept would seem to be supported by the occurrence of silent ischemia in the setting of stable, unstable, or variant angina, despite differing pathophysiologic conditions. Ischemic events have important prognostic significance; unfortunately, many are unrecognized by patients. The question whether the treatment of ischemic events will improve prognosis remains a matter of debate. PMID- 1449094 TI - New insights in measurement of myocardial ischemia. AB - Myocardial ischemia may be defined as myocellular dysfunction resulting from hypoxia usually due to limited coronary blood flow. The methods commonly used to make a diagnosis of myocardial ischemia employ either clinical findings (e.g., angina, myocardial infarction) or signals from laboratory tests. Since ischemia is often clinically silent and since clinical events related to ischemia may be catastrophic (i.e., myocardial infarction and sudden death), physicians are dependent on tests using various targeted signals. These signals, however, do not actually provide quantitative measurements of the degree of ischemia or related myocardial dysfunction. Nevertheless, the functional abnormalities reflected by these signals can identify patients at high or low risk for adverse outcomes related to ischemia. So, in this sense, these signals can be used to support the diagnosis of ischemia as well as evaluate its importance in a given patient. The most commonly used signal is an ST-segment shift evident on the electrocardiogram (ECG). When this is horizontal or downsloping and > or = 10 mm, this is often, but not always, due to myocardial ischemia. Although assessment of the exercise stress ECG offers several advantages over assessment of the resting ECG, the standard Bruce protocol is associated with notable shortcomings that become apparent when an attempt is made to assess the effects of a treatment on the ST segment signal. These might be surmounted by use of a continuous ramp-type protocol. Ambulatory ECG monitoring is growing in importance in the wake of increasing awareness of the different daily life circumstances that are associated with ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449095 TI - Treatment of chronic stable angina pectoris. AB - Patients with angina pectoris may be stratified into low- or high-risk categories on the basis of clinical findings and a careful workup, possibly including nuclear imaging of stress-induced abnormal perfusion or contractile patterns and coronary angiography. High-risk patients may require revascularization by angioplasty or bypass surgery, whereas low-risk patients can be managed medically. It is important to consider the impact of various anti-ischemic drugs on the myocardial demand-supply equation. A recent study indicated that the combination of a beta blocker plus isosorbide mononitrate is more effective in increasing exercise duration than is either the combination of a beta blocker and a calcium antagonist or triple therapy. In patients with single-vessel disease, angioplasty has been shown to be more effective than medical therapy in relieving symptoms, but the incidence of restenosis and the associated costs are high. Surgery favorably affects mortality in patients with left main coronary artery disease or 3-vessel disease with left ventricular impairment. New evidence suggests that endothelial dysfunction may play a more important role in chronic stable angina pectoris than has been appreciated and that such dysfunction may be treated with nitrates. PMID- 1449096 TI - Pathophysiology of atherosclerosis. AB - New experimental evidence has shed light on a number of fundamental processes that contribute to atherosclerotic plaque formation. Recent data suggest that oxidized low-density lipoprotein (LDL) may be more avidly bound and taken up by macrophages, and thus more atherogenic, than unmodified LDL. A subclass of LDL, lipoprotein(a), is also of interest with respect to atherogenic potential, particularly since it has a plasminogen-like moiety as part of its structure. It may promote platelet aggregation and thrombus formation and thereby contribute to atherosclerotic plaque growth. Hypercholesterolemia, hypertension, and possibly other factors may induce changes in endothelial structure and function, which appear to be relatively early events associated with arterial injury. Smooth muscle cell proliferation and accumulation are hallmarks of arterial lesions induced by both hypertension and hypercholesterolemia, and several growth factors have been potentially implicated in these responses. Hypertension by itself causes arterial damage, but it does not appear to induce atherosclerosis when plasma lipid concentrations are low. In combination with hypercholesterolemia, however, it is a potent promoter of atherogenesis, and the mechanisms for this more-than-addictive effect are now the focus of considerable investigative attention. PMID- 1449097 TI - Treatment of unstable angina pectoris. AB - Unstable angina pectoris may be manifested as new-onset angina, a change in the anginal pattern, pain at rest with associated electrocardiographic (ECG) changes, or postinfarction angina. Of these, pain at rest with ischemic ECG changes is known to be associated with the poorest prognosis. The pathogenesis of unstable angina pectoris involves a combination of a fixed atherosclerotic obstruction and a dynamic component related to coronary vasoconstriction, thrombus formation, or both. Long-acting nitrates, inhibitors of platelet aggregation, beta blockers, and calcium antagonists are among the agents that have been shown to be effective in the medical management of unstable angina. A study now in progress is evaluating the routine use of thrombolytic therapy for this indication. Although alleviation of symptoms and prevention of death and myocardial infarction are important therapeutic goals, the overall efficacy of a particular medical therapy can best be assessed by objective evaluation of its ability to control ischemia, using such techniques as exercise scintigraphy and ambulatory ECG monitoring. Cardiac catheterization and revascularization are indicated for patients with unstable angina who continue to experience symptoms or who show evidence of silent ischemia despite medical therapy. A study is under way to determine the advisability of routine revascularization of such patients. Revascularization will provide symptomatic relief in most patients with unstable angina and may prolong survival and improve left ventricular function in certain subsets. PMID- 1449098 TI - Pharmacologic mechanisms of nitrates in myocardial ischemia. AB - Nitrates exert both hemodynamic and nonhemodynamic effects that help explain the mechanisms by which these drugs benefit patients with myocardial ischemia. The hemodynamic effects of nitrates include relaxation of conduit arteries, increased arterial compliance, increased venous capacitance, dilation of collateral vessels in the myocardium, and, possibly, increased myocardial compliance. A growing body of evidence suggests that the nonhemodynamic effects of these agents include inhibition of vascular smooth muscle growth and of myocyte hypertrophy and ventricular remodeling. Since endothelial function appears to be abnormal in patients with myocardial ischemia and nitrates replicate many of the effects of endothelium-derived relaxing factor, these drugs may be viewed as a pharmacologic replacement for deficient endogenous activity. PMID- 1449099 TI - Tolerance, rebound, and time-zero effect of nitrate therapy. AB - Both nitroglycerin and long-acting nitrates have proved effective in treating acute anginal pain. In recent years, however, development of tolerance with the continuous use of these agents has been documented. A pilot study demonstrated attenuation of the therapeutic effect of high-dose, continuous transdermal nitroglycerin therapy, despite adequate plasma nitroglycerin levels. In a subsequent, larger Transdermal Nitroglycerin Cooperative Study, evidence of tolerance was detected within 24 hours of initiation of continuous nitroglycerin patch therapy at several different dose levels. Sustained pharmacologic activity has been achieved with the intermittent use of transdermal nitroglycerin, usually for 12 hours followed by a 12-hour drug-free period. When the patch is discontinued, however, some patients experience exacerbation, or rebound, of anginal symptoms and a worsening of exercise tolerance at the end of the drug free period. Additional clinical research is therefore needed to determine the optimal intermittent dosing strategy. PMID- 1449100 TI - Possible mechanisms of nitrate tolerance. AB - Prolonged exposure to organic nitrates has been shown to lead to the rapid development of tolerance to the peripheral and coronary vasodilatory effects of these drugs. As a result of this phenomenon, the hemodynamic and anti-ischemic effects of nitrates may be rapidly attenuated in patients with ischemic heart disease, congestive heart failure, or both. This nitrate tolerance appears to be both dose- and time-dependent. Likely mechanisms proposed for its development are multifactorial and include depletion of sulfhydryl groups, a nitrate-mediated increase in blood volume, and neurohormonal stimulation with activation of vasoconstrictive mechanisms. PMID- 1449101 TI - Rationale for intermittent nitrate therapy. AB - Tolerance to the pharmacologic and therapeutic effects of nitrate therapy is now well established. This phenomenon may be defined as either a decreased response to a given amount of nitrate or the need for an increased amount of nitrate to maintain a constant effect. Tolerance has been demonstrated with all forms of nitrate therapy that maintain continuous blood levels of the drug, including frequent oral dosing, constant intravenous infusion, and continuous transdermal delivery. It can develop rapidly after only a few doses of a nitrate preparation and tends to be partial rather than absolute. Strategies for the prevention of nitrate tolerance include the avoidance of maximum nitrate doses and the use of intermittent nitrate dosing regimens. Providing a relatively brief nitrate-free interval restores vascular responsiveness to nitrates, most likely due to a recovery of the metabolic mechanisms responsible for the therapeutic effect of these drugs. The duration of this period of nitrate abstinence varies, depending on the nitrate preparation used but is generally in the range of 8-12 hours. Such intermittent therapy not only reduces the risk of nitrate tolerance, but also provides a convenient approach to outpatient management. PMID- 1449102 TI - Pharmacokinetics of isosorbide mononitrate. AB - Pharmacokinetic studies show that isosorbide mononitrate is rapidly absorbed after oral administration, reaches peak concentrations within an hour, undergoes no significant first-pass metabolism, and is virtually 100% bioavailable. The half-life is approximately 5 hours, the volume of distribution is 0.62 liter/kg, and the systemic clearance is 115 mL/min. Only 1-2% of an orally administered dose is excreted unchanged in the urine, with the remainder being eliminated as inactive metabolites. Isosorbide mononitrate follows dose-linear kinetics after single and multiple doses. Its pharmacokinetic profile is consistent and highly reproducible and is unchanged in the elderly and in patients with coronary artery disease, renal failure, or liver cirrhosis. An asymmetrical dosage regimen of isosorbide mononitrate has been shown to provide antianginal efficacy for at least 12 hours. Because asymmetrical dosing creates irregular, sawtooth-like changes in plasma concentrations and a fall below a critical threshold level during the night, tolerance does not develop. PMID- 1449103 TI - Efficacy of isosorbide mononitrate in angina pectoris. AB - The rapid development of tolerance has limited the applicability of oral and transdermal nitrates in the long-term management of patients with chronic stable angina pectoris. Recent well-controlled trials have demonstrated that asymmetrical, or eccentric, dosing of oral isosorbide mononitrate, in which 20-mg doses are taken at 8 A.M. and 3 P.M., provides at least 12 hours of antianginal coverage. There is no evidence for the development of tolerance with this schedule, which allows for a 17-hour nitrate withdrawal period. Likewise, the asymmetrical 20-mg twice daily regimen has not been associated with the zero-hour effect that has been reported with higher oral doses of isosorbide mononitrate and with intermittent nitroglycerin patch therapy. This approach also avoids the development of a clinical rebound phenomenon, as measured by increased episodes of angina and nitroglycerin consumption, compared with the pretreatment period, during the nitrate-free interval at night and the early hours of the morning. PMID- 1449104 TI - Optimizing antianginal therapy: consensus guidelines. PMID- 1449105 TI - New insights into the management of myocardial ischemia. AB - Episodes of ST depression are closely related to transient decreases in regional myocardial perfusion during physical or mental stress. At the onset of these events, there is transient constriction of atherosclerotic stenoses, with an increase in myocardial demand as reflected by increases in heart rate and blood pressure. Recent research has shown that normal epicardial coronary arteries respond to these provocations and to increasing blood flow with progressive vasodilation. In contrast, atherosclerotic vessels lose this ability to dilate and may show paradoxical constriction. This abnormal constriction parallels the response of the arteries to acetylcholine, which can be used to assess the ability of the coronary endothelium to regulate vasodilation. The loss of endothelium-dependent vasodilation appears to be an important functional manifestation of coronary atherosclerosis and a potential triggering mechanism for transient ischemia. Dysfunctional endothelium may also result in a procoagulant surface, with cell adherence and local thrombus formation. Restoration of normal endothelial function is likely to emerge as an important therapeutic objective in the management of myocardial ischemia and coronary atherosclerosis. PMID- 1449106 TI - A phase I study of high-dose cisplatin, prolonged infusion 5-fluorouracil, and concomitant conventional fraction radiation therapy in patients with inoperable squamous cell carcinoma of the head and neck. AB - Cisplatin (CDDP) and 5-fluorouracil (5-FU) have been used alone, in combination, and in various doses and sequences with radiation therapy in attempts to improve local control and survival of patients with advanced head and neck cancer. This study was undertaken to determine the toxicity and maximum tolerated dose of high dose CDDP plus prolonged infusion 5-FU with concomitant conventional radiation therapy. Twenty-two patients with inoperable Stage III and IV squamous cell cancer were treated with CDDP (30 or 35 mg/m2 for 5 days every 4 weeks for three courses) and 5-FU (200 or 300 mg/m2 per day continuous i.v. infusion for 12 weeks) with concomitant conventional radiation therapy. This aggressive treatment regimen is accompanied by severe mucositis, myelosuppression, and chronic neuropathy. CDDP, 35 mg/m2/day x 5, and 200 mg/m2/day of 5-FU infused over 12 weeks were identified as potential doses for future Phase II studies. PMID- 1449107 TI - Phase I study of 5-fluorouracil with folinic acid combined with recombinant human granulocyte-macrophage colony-stimulating factor. AB - A Phase I study was conducted to determine whether the addition of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to a combined 5 fluorouracil (5-FU) and folinic acid (FA) regimen would allow an escalated starting dose of 5-FU. FA (500 mg/m2) was administered as a 2-hour infusion on days 1 through 5, with 5-FU administered as a bolus injection 1 hour after the initiation of FA. Fifteen patients were enrolled in the trial; six were entered at a dose level of 375 mg/m2 of 5-FU, six at 450 mg/m2, and three at 540 mg/m2. rhGM-CSF was administered subcutaneously on days 6 through 15. A course of therapy was repeated every 28 days. Serious toxicity was observed at 450 mg/m2, with two patients developing grade 3 mucositis and one, grade 4 mucositis. Dose limiting toxicity occurred at 540 mg/m2, at which point three patients developed grade 4 mucositis. One patient with metastatic colon cancer who received 5-FU at 540 mg/m2 achieved a partial response. Because of this persistent mucositis, the addition of rhGM-CSF used in this schedule would not allow an increased starting dose of 5-FU. PMID- 1449108 TI - Radiation therapy in the treatment of pituitary adenomas. AB - Seventy-eight patients with pituitary adenomas were seen in the Department of Radiation Oncology at Hahnemann University between 1961 and 1986. Most were treated with megavoltage photons with or without prior surgery. In this group, 68 patients were followed: 39 were treated with radiation therapy (RT) alone, and 29 were treated with a combination of surgery and RT (S/RT). Patients were followed for 2 to 20 years. Of 68 patients, (97%) experienced complete response to treatment; 86% of the RT patients remained free of disease at 5 and 10 years. In the S/RT group, 100% and 94% remained free of disease at 5 and 10 years, respectively. Total disease-free survivals at 5 and 10 years were, respectively, 91% and 89%. The majority of the failures occurring in the RT group were with growth hormone-secreting tumors and Cushing's disease. Of the 7 patients that failed or recurred (time to recurrence: 1-16 years posttreatment), 6 have been followed: 4 were treated with surgery, 1 with RT, and 1 with S/RT. All 6 have remained free of disease since salvage, with 2- to 14-year follow-up periods. Serious morbidity and mortality have been reported previously with bitemporal field radiation using kilovoltage and low megavoltage RT. However, there was no temporal lobe necrosis or death in any of the patients in this study. PMID- 1449109 TI - A phase II clinical trial evaluating the use of two sequential, four-drug combination chemotherapy regimens in ambulatory bronchogenic adenocarcinoma patients. AB - Forty-three ambulatory patients with locally advanced or metastatic bronchogenic adenocarcinoma were sequentially treated with two potentially mutually non-cross resistant chemotherapy regimens. A new regimen, MVPF (mitomycin-c, vinblastine, procarbazine, and 5-fluorouracil), was given until progressive disease occurred. Then, a second regimen--MOCC (methotrexate, vincristine [Oncovin], cyclophosphamide, and CCNU)--was initiated. At further progression, regional disease patients received radiotherapy, whereas extensive disease patients received Phase II agents. Of the 43 patients entered on the study, 40 were evaluable. Three patients withdrew early due to poor tolerance of the regimen. The response rate for MVPF was 33% (12 of 40 PR, 1 of 40 CR) compared to a 4% (1 of 23 PR) response for MOCC (difference: p < or = .03), for a total response rate of 35%. Although there was an initial improvement in survival for responders (31.7 weeks) versus nonresponders (15.7 weeks) at the 75th percentile (p < or = .05), there was no significant difference in median survival. The hematologic toxicity was equivalent for both groups, whereas nonhematologic toxicity revealed a high incidence of nausea and vomiting in the MVPF group. It is concluded that this approach lent itself well to ambulatory care, and MVPF could be considered an alternative to cyclophosphamide-based regimens. However, the absence of a meaningful CR rate and lack of influence of response on median survival were factors limiting its effectiveness. PMID- 1449110 TI - Lack of significant activity of 2'-deoxycoformycin alone or in combination with adenine arabinoside in relapsed childhood acute lymphoblastic leukemia. A randomized phase II trial from the Childrens Cancer Study Group. AB - Forty-nine children with recurrent acute lymphoblastic leukemia (ALL) were entered into a randomized Phase II trial evaluating 2'-deoxycoformycin (dCF) alone or in combination with adenine arabinoside (ara-A). 2'-Deoxycoformycin is an inhibitor of adenosine deaminase (ADA), an enzyme found in relatively high amounts in malignant lymphoid cells. Ara-A inhibits DNA polymerase and DNA synthesis. Because its efficacy in vivo as an anticancer agent is limited by its rapid inactivation by ADA, ara-A was combined with dCF to produce cytoreductive levels of ara-A. Twenty-four patients were assigned to receive dCF alone and 25 to receive the combination. No patient responded to dCF alone, and one patient developed a complete remission after treatment with the combination. The toxicity of dCF alone was minimal, except for one patient who became obtunded on day 5 following the first cycle of therapy. In contrast, five patients developed severe toxicity with the combination, including renal failure (three patients), hepatic failure (three patients), and neurologic toxicity (two patients). These results indicate that, at the doses and schedule used in this study, the combination of dCF and ara-A has significant toxicity and minimal activity against recurrent ALL in children. PMID- 1449111 TI - 5-fluorouracil and low-dose leucovorin in the treatment of recurrent epithelial ovarian carcinoma. A phase II trial of the Gynecologic Oncology Group. AB - Twenty-one patients with recurrent epithelial ovarian carcinoma not amenable to cure with further surgery or radiotherapy were entered into a Phase II trial utilizing i.v. leucovorin at 20 mg/m2 followed by i.v. 5-fluorouracil at 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. Twenty-one patients were entered. Of these, 20 were eligible for toxicity assessment and 19 for response. Five had received prior radiotherapy, and all had received prior cisplatin-based chemotherapy. There was one patient response (5.3%; 95% confidence intervals for response of 0% to 26%). Toxicity was moderate with 5 of 20 (25%) grade 3 or 4 leukopenia, 12 of 20 (60%) grade 3 or 4 granulocytopenia, 1 of 20 (5%) grade 3 thrombocytopenia, 5 of 20 (25%) grade 3 GI toxicity, and 2 of 20 (10%) grade 3 neurotoxicity. There was one toxic death in a patient who developed granulocytopenia and pneumonia after her third course of treatment. This dose schedule of 5-fluorouracil and leucovorin has minimal activity in patients with recurrent epithelial ovarian carcinoma who have received prior cisplatin chemotherapy. PMID- 1449112 TI - 5-fluorouracil and low-dose leucovorin in the treatment of recurrent squamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group. AB - Twenty-eight patients with recurrent squamous carcinoma of the cervix not amenable to cure by further surgery or radiation therapy were entered into a Phase II trial utilizing i.v. leucovorin 20 mg/m2 followed by 5-fluorouracil 425 mg/m2 administered daily for 5 days every 4 weeks for the first two courses and then every 5 weeks. One patient never received therapy, and three are inevaluable for response; therefore, 27 patients were evaluable for toxicity and 24 for response. Twenty-three patients had received prior radiotherapy, and 16 had received prior chemotherapy. There was one partial response 4.2% (95% confidence intervals for a response of 0 to 21%). Although toxicity was acceptable with 11 of 27 (41%) grade 3 or 4 leukopenia, 1 of 27 (4%) grade 3 thrombocytopenia, and 3 of 27 (11%) grade 3 or 4 gastrointestinal toxicity, this dose schedule of 5 fluorouracil and leucovorin has minimal activity in recurrent squamous carcinoma of the cervix. PMID- 1449113 TI - Nonbacterial thrombotic endocarditis clinically mimicking veno-occlusive disease of the liver complicating autologous bone marrow transplantation. AB - Nonbacterial thrombotic endocarditis is an uncommon, but well-described, complication of bone marrow transplantation. We describe a case of nonbacterial thrombotic endocarditis following autologous bone marrow transplantation that was marked by weight gain, hepatomegaly, ascites, and extreme hyperbilirubinemia leading to a clinical diagnosis of hepatic veno-occlusive disease. Autopsy revealed nonbacterial thrombotic endocarditis of the tricuspid and pulmonic valves, and passive congestion of the liver, but there was no evidence of veno occlusive disease. We discuss the pathophysiology and clinical features of nonbacterial thrombotic endocarditis and review its occurrence in association with bone marrow transplantation. Nonbacterial thrombotic endocarditis is often difficult to detect clinically and should be a diagnostic consideration in patients who develop systemic emboli or congestive heart failure after bone marrow transplantation. PMID- 1449114 TI - A phase II study of cisplatinum and continuous infusion 5-fluorouracil for metastatic melanoma. AB - Advanced or metastatic melanoma responds poorly to chemotherapy, which has no impact on survival. Responses have been recorded using cisplatinum as a single agent. This study tested the established combination of cisplatinum 100 mg/m2 and 5-fluorouracil 1 g/m2/day continuously intravenously for 5 days repeated every 3 weeks in patients with disseminated melanoma. Twenty-nine patients, 13 having received no prior systemic chemotherapy, received 49 cycles of therapy (median 1, range 1-4). Only one previously untreated patient achieved a partial response with a failure-free survival of 6.5 months and an overall survival of 7.7 months from the commencement of therapy. The major toxicities were nausea and vomiting, (grade 3 in eight patients), stomatitis (grade 4 in two patients, grade 3 in two patients), and myelosuppression. The study showed that cisplatin and 5 fluorouracil have a low order of activity in patients with advanced or disseminated melanoma. PMID- 1449115 TI - Treatment of Langerhans cell histiocytosis in children with etoposide. AB - Ten children with Langerhans cell histiocytosis (LCH) were treated with etoposide. For five patients, this was the initial diagnosis. The other five had failed to respond to previous therapies. Etoposide (100 mg/m2) was given intravenously twice a week for 4 weeks, followed by maintenance therapy every 2 to 4 weeks for 2 years. All 10 patients responded to etoposide, and 6 of them (60%) have been in complete remission for 3 to 36 months without any side effects. One patient relapsed with diabetes insipidus, one with a soft tissue mass, and two others developed multiple bone lesions. Chemotherapy with etoposide appears to be effective and safe for the treatment of children with systemic LCH. PMID- 1449116 TI - Systemic infusion versus bolus chemotherapy with 5-fluorouracil in measurable metastatic colorectal cancer. AB - From January 31, 1986 to January 31, 1989, 184 eligible patients were enrolled in a randomized study of either infusional or bolus 5-fluorouracil (5-FU) for the treatment of metastatic measurable colorectal cancer. Infusion was administered at an escalated dose schedule starting at 350 mg/m2 per day for 2 weeks with a 2 week rest period on a monthly basis, while bolus 5-FU was started at 400-450 mg/m2 for 5 days every 28 days. In these chemotherapy-naive patients with good performance status, the infusion arm produced a response in 11 of 88 patients versus 6 of 82 in the bolus arm (p = 0.384). Progression free survival was significantly longer (p = 0.0139) in the infusion group (3.8 versus 2.3 months), but no significant difference in survival was observed (p = 0.207). As expected, the toxicities of the regimens were different in character, but each had approximately a 20% incidence of significant toxicities. Neither of these methods of administering fluorouracil results in an exceptional response rate, nor does the infusion have an impact on survival as compared to the bolus route. If this type of complicated infusional approach is to continue, especially with increasing dosage (which could be accomplished on our schedule), randomized studies with survival as an endpoint must remain the gold standard. PMID- 1449117 TI - Phase II evaluation of iproplatin in patients with advanced gastric and pancreatic cancer. AB - A total of 48 patients with measurable advanced gastric adenocarcinoma (n = 16) or adenocarcinoma of the exocrine pancreas (n = 32) were prospectively treated with iproplatin at a starting dose of 270 mg/m2 intravenously over 2 hours. The dose was repeated every 28 days, and dose escalations or reductions were made on the basis of toxicity in the preceding course. No patient with gastric carcinoma achieved either a complete or partial response. One partial response and two complete responses were seen with pancreatic adenocarcinoma for an overall response rate of 10%. One patient has remained free of disease for more than 2 years. The major toxicities were granulocytopenia, thrombocytopenia, nausea, vomiting, and diarrhea. All toxicities were reversible upon discontinuation of the drug. On the basis of this trial, we conclude that iproplatin has no substantive activity in advanced gastric or pancreatic carcinomas. PMID- 1449118 TI - Successful therapy of peritoneal mesothelioma with intraperitoneal chemotherapy alone. A case report. AB - Malignant peritoneal mesothelioma is a disease that remains relatively refractory to conventional intravenous chemotherapy with currently available agents. Single agent and combination chemotherapy offer a response rate of 20%. Direct intraperitoneal administration of some chemotherapeutic agents results in a significant pharmacologic advantage with much greater area under the concentration versus time curve (AUC). We report a case of a patient with peritoneal mesothelioma treated with combination intraperitoneal cisplatin and Ara-C who achieved a pathologic complete remission. This patient is still alive and has been in complete remission for 53 months. This combination of intraperitoneal chemotherapy deserves further evaluation in malignant mesothelioma. PMID- 1449119 TI - DAE (daunorubicin, Ara-C, and etoposide) and intermediate dose Ara-C for remission induction and consolidation treatment of adult patients with acute myeloid leukemia. AB - Fifty-one patients (age 18-73 years) with acute myeloid leukemia were treated with daunorubicin, cytarabine, and etoposide in an age-adjusted protocol, with patients older than 50 receiving fewer days of therapy. Complete remission (CR) occurred in 66% of the patients (34 of 51 patients). Patients 50 years of age and younger achieved a 74% CR rate (23 of 31 patients) compared to a 55% CR rate (11 of 20 patients) in older patients. Of the 34 complete responders, 11 (32%) refused consolidation therapy and received traditional Chinese herbal medicine. All of these 11 patients relapsed after a short remission duration (median, 3.8 months) and died. The median remission duration and median overall survival of 23 complete responders receiving at least two courses of consolidation therapy were 10.1 and 19.8 months, respectively. The actuarial 3-year disease-free survival for these 23 complete responders was 21 +/- 9%. Myelosuppression was the major toxicity, and nonhematological side effects were acceptable. The regimen appeared to have acceptable toxicity, and its efficacy was comparable with that of standard regimens with long-term maintenance therapy. PMID- 1449120 TI - Substance use and work disabilities among a general population. AB - Using data derived from a representative survey of 869 Ontario adults, we examined the association between work disabilities and substance use, i.e., drinking, alcohol problems, sleeping pills, and tranquilizers. Overall, we found a significant association between substance use and disability. For alcohol problems, we found that those with moderate limitations reported the greatest number of problems, holding constant age, gender, income, and frequency of drinking. For the use of sleeping pills and especially tranquilizers, we found a strong positive relationship to limitation status. A number of significant interactions involving tranquilizer use showed that two groups, females with total limitations and those aged over 40 years with sensory disabilities, reported exceptionally high rates of tranquilizer use. PMID- 1449121 TI - High-risk sexual behaviors of intravenous drug users in- and out-of-treatment: implications for the spread of HIV infection. AB - This paper examines the sexual behaviors of 255 intravenous drug users (IVDUs) to assess the potential for the sexual transmission of HIV and to examine differences in sexual behaviors between in- and out-of-treatment IVDUs. In treatment subjects (N = 152) were a random sample of clients at a large, publicly funded methadone maintenance program. Out-of-treatment subjects (N = 103) were recruited through a chain referral technique, using the in-treatment subjects. Forty-five percent of the study subjects reported multiple partners and 32% reported exchanging sex for money or drugs in the preceding 6 months. Fifty-three percent reported no use of condoms. After controlling for demographic differences between the in- and out-of-treatment groups, out-of-treatment IVDUs reported significantly more partners than in-treatment IVDUs (4.6 vs 2.3, significant t < 0.01), and more often had exchanged sex for money or drugs (44 vs 26%, relative odds 1.8, p < .05). In- and out-of-treatment subjects did not differ with respect to condom use. We conclude that IVDUs both in- and out-of-treatment continue to be at risk of contracting and spreading HIV infection through sexual behaviors, and that being in drug treatment is associated with a lower incidence of high risk sexual behaviors. PMID- 1449122 TI - Abuse of monoamine oxidase inhibitors. AB - Monoamine oxidase inhibitors, like other antidepressants, generally are considered free of risk for abuse. There is, however, some evidence that MAOIs possess dependence and abuse potential for some patients. We will review the available literature and describe three current cases. Recommendations for treatment are discussed briefly. PMID- 1449123 TI - Assessing treatment effects through changes in perceptions and cognitive organization. AB - This investigation tested the Associative Group Analysis (AGA) for its analytic sensitivity in assessing perceptions and attitudes and in mapping changes in cognitive organization indicative of substance abuse. Based on inferences drawn from the distributions of thousands of spontaneous, free associations elicited by strategically selected stimulus themes, AGA offers an unstructured approach to assess images and meanings, and to map systems of mental representation evasive to the more direct methods of using questions or scales. This article compares pretreatment and posttreatment samples, tracing the psychosocial effects of treatment. The investigations focus on variables related to substance abuse such as self-image, social nexus, and perceptions of illicit substances. The results indicate a sensitive approach, useful in treatment evaluation. PMID- 1449124 TI - The relationship of pretreatment family functioning to drinking behavior during follow-up by alcoholic patients. AB - The relationship of alcoholics' perceptions of the pretreatment functioning of their families to drinking outcomes during an 18-month follow-up was examined. Family functioning was hypothesized to be predictive of drinking behavior, particularly in subjects with low assertion of autonomy scores. These individuals report greater dependency and attachment, and therefore might be more affected by the state of important relationships. The results indicated that with low autonomy male alcoholics, greater family dysfunction predicted significantly fewer days abstinent during Months 1-6 and 13-18 and more severe drinking episodes during the first year of the follow-up. In the high autonomy males, family dysfunction was unrelated to subsequent drinking behavior. In women, on the other hand, greater family dysfunction predicted more days abstinent in those high in autonomy and was unrelated to the drinking behavior of those low in autonomy. Implications for patient-treatment matching, differences between male and female alcoholics, and the need for additional studies of family functioning and drinking behavior in women are discussed. PMID- 1449125 TI - Alcohol norms and expectations as predictors of alcohol use and problems in a college student sample. AB - Two-hundred thirty-one alcohol-using college students completed a questionnaire on their levels of alcohol use, moderate to severe problems with alcohol use, expectations of the effects of alcohol on their own and others' moods and behaviors, the desirability of these effects, norms of significant others for levels of alcohol use and the subject's desire to comply with these norms, reasons for drinking and not drinking alcohol, and a personality measure. Expectations of alcohol effects, norms of significant others, and reasons for drinking and not drinking alcohol were all significant independent predictors of alcohol use and problems with alcohol use. Expectation x desirability of effects formulations and norms x desire to comply with norms formulations did not improve the predictive power of the expectations and norms scales. PMID- 1449126 TI - Cognitive motivations for drinking among alcoholics: factor structure and correlates. AB - The aims of this study were to: a) Identify factors reflecting reasons for drinking and expectancies regarding the effects of drinking among inpatient alcoholics; b) Examine the relationship between these cognitive "motivations" for drinking and both patterns of alcohol consumption and various personal and social consequences of consumption. The factors which emerged relate to negative mood reduction, positive mood enhancement, and social functioning. Although the factors identified in this investigation were not associated with quantity of alcohol consumed, small to moderate associations were found between scores on three of four factors and a variety of adverse physical and occupational consequences of alcohol abuse. PMID- 1449127 TI - Idiopathic achalasia: are there different types? PMID- 1449128 TI - Hepatotoxicity of nonsteroidal anti-inflammatory drugs. AB - The steady increase in nonsteroidal anti-inflammatory drug (NSAID) use over the past decade has been associated with an increased awareness of the gastrointestinal complications of these agents. As a result, several reviews on this topic have been published. Associated with the increased recognition of the untoward gastrointestinal consequences of NSAID use has been an increasing awareness of the untoward hepatic consequences of NSAID use. Nonetheless, many physicians either remain unaware of the hepatotoxic potential of NSAIDs or are unsure which agents are either safer or associated with a greater risk for hepatotoxicity. The following is an overview of the hepatotoxicity of NSAIDs that identifies both the type and severity of such reactions, where sufficient data exist to allow such judgements to be made. PMID- 1449129 TI - Return of esophageal peristalsis after nifedipine therapy in patients with idiopathic esophageal achalasia. AB - This study was carried out to demonstrate the possible return of esophageal peristalsis in patients affected by esophageal achalasia chronically treated with sublingual nifedipine and to investigate which parameters are correlated with the return of peristalsis. Thirty-two patients were treated with sublingual nifedipine 10-20 mg taken 30 min before meals. A clinical and manometric evaluation was performed before and after 6 months of therapy. Before treatment, in no patient was peristaltic activity recorded. After 6 months, peristalsis was observed in six patients. In this group, no pretreatment manometric parameter was different from that of the remaining achalasic patients; only the clinical history of dysphagia was significantly shorter (p < 0.001) and the esophageal diameter significantly less (p < 0.001). In conclusion, chronic treatment with sublingual nifedipine can induce a return of esophageal peristalsis in patients with a short clinical history of disease and slightly dilated esophagus. PMID- 1449130 TI - The importance of fluoroscopic guidance for Maloney dilation. AB - One hundred and forty-five patients were evaluated for the importance of fluoroscopic monitoring during Maloney esophageal dilation. In 35 patients (24%), fluoroscopy altered the dilation technique. Dilation of peptic strictures (27 of 75, 36%) was much more likely to be affected by fluoroscopy than Schatzki's rings (eight of 70, 11%, p < 0.05). Patients whose stricture was altered by fluoroscopy also had larger size hiatal hernias (6.5 vs. 4.3 cm, p < 0.05). Patients with Schatzki's ring with a hiatal hernia size of less than or equal to 4.0 cm did not benefit from fluoroscopy. In 26 of 35 cases, successful redirection of the dilator and passage under fluoroscopy was accomplished. In nine patients, Maloney dilation was impossible, and use of Savary wire-guided dilators was needed. We had no morbidity and mortality. We advise the use of fluoroscopy for Maloney dilation for peptic strictures and for large hiatal hernias. PMID- 1449131 TI - Abnormal upper esophageal sphincter function in achalasia. AB - We describe the results of pharyngeal and upper esophageal sphincter (UES) manometry, using new solid-state computerized technology in 19 patients with achalasia, compared with 14 healthy controls. The major manometric finding in achalasia is an increased residual pressure in the UES. Other differences seen in patients with achalasia include a reduction in the duration of UES relaxation with swallowing and a more rapid onset of pharyngeal contraction after UES relaxation. We review previous descriptions of suspected pharyngeal and UES abnormalities in achalasia and compare them to our own. PMID- 1449132 TI - Meta-analysis of the efficacy of antibiotic therapy in eradicating Helicobacter pylori. AB - Despite numerous Helicobacter pylori treatment studies, the optimum regimen(s) for its eradication remain unclear. Our objective was to determine systematically which regimen(s) gave the best pooled eradication rates, by using meta-analysis methodology. A total of 27 studies were identified. Pooled eradication rates for single (18.6%), double (48.2%), and triple therapy (82.3%) were statistically highly different (p < 0.0005). Eradication rates with amoxicillin (23.0%) and bismuth compounds (19.6%) were equivalent. Combined treatment with bismuth+metronidazole was better than bismuth+amoxicillin (55.1% vs. 43.7%, p = 0.049). Triple therapy with bismuth+metronidazole+tetracycline gave a statistically higher eradication rate (94.1%) than bismuth+metronidazole+amoxicillin (73.1%, p < 0.0005). Despite increased side effects with multiple antibiotic regimens, patients tolerated these well, without significant drop-out. The combination of bismuth, metronidazole, and tetracycline gives the best eradication rate, but the optimal doses and duration of treatment have yet to be determined. Further studies are necessary to explore factors such as antibiotic resistance and drug compliance as important factors affecting antibiotic efficacy. PMID- 1449134 TI - An unrecognized etiology for pyogenic hepatic abscesses in normal hosts: dental disease. AB - Cryptogenic pyogenic hepatic abscesses are a diagnosis of exclusion. We have identified two patients with severe dental disease at the time of the diagnosis of their liver abscess. In both cases, oral flora was cultured from the abscess. Unlike a previous report, both patients were immunocompetent. When compared with a group of patients with liver abscesses and diverticulitis, two differences were found. In contrast to the single abscesses seen in 10 of 10 patients with diverticulitis, the patients with dental disease had multiple abscesses (p < 0.02). In addition, Fusobacterium nucleatum was cultured from both dental disease associated abscesses but only one of the diverticulitis associated liver abscesses (p < 0.05). If a liver abscess is thought to be cryptogenic, a thorough dental exam is recommended. PMID- 1449133 TI - Helicobacter pylori infection in dental workers: a seroepidemiology study. AB - The finding of Helicobacter pylori in dental plaque suggested that dental workers may be at increased risk of acquiring H. pylori infection from occupational exposure. A cross-sectional survey of 239 dental workers from 37 Texas cities (including 89 dentists, 44 dental hygienists, 98 dental assistants, and eight dental students) was conducted. H. pylori infection was determined by the presence of IgG antibodies to H. pylori, using a specific and sensitive ELISA. Participants ranged in age from 19 to 72 yr (mean 34 yr) and the duration of dental practice ranged from 1 to 48 yr (mean 12 yr). Type of dental occupation, duration of practice, type of practice (public or private), instrument used for cleaning teeth (ultrasonic scaler or curette), and prevalence of upper gastrointestinal symptoms were determined by self-administered questionnaires and interviews. Eighty-two percent had no symptoms referable to the upper gastrointestinal tract. The overall prevalence of H. pylori infection was 24%: 17% in dentists, 18% in dental hygienists, 34% in dental assistants, and 25% in dental students. The prevalence increased significantly with age (p < 0.05). The prevalence of H. pylori infection was significantly higher in non-whites, 29 of 63 (46%), than whites, 29 of 176 (16%) (p < 0.001). Logistic regression analysis (dependent variable H. pylori) revealed no significant association between H. pylori infection and the type, duration, or volume of practice, or the type of cleaning instrument used. We conclude that dental workers are not at increased risk to H. pylori infection. PMID- 1449135 TI - Safety and efficacy of high kV biliary lithotripsy: preliminary experience. AB - Despite intense interest in laparoscopic cholecystectomy, biliary lithotripsy (BL), by avoiding the need for general anesthesia, could remain a useful alternative in approximately 10% of patients with symptomatic gallstones. The poor stone clearance rates reported by the Dornier National Biliary Lithotripsy Study has led to disenchantment with biliary lithotripsy. However, the results may reflect the relatively low kV (18.7 +/- 1.7) used. We have compared symptomatic gallbladder stone/cholecystolithiasis patients with one to five stones of aggregate diameter < 60 mm treated with one to three sessions on an MPLS 9000 (Dornier) lithotripter at moderate kV (22.7 +/- 1.7 kV; mean number of shocks 1473 +/- 356) with a similar group treated with high kV (26 kV, mean number of shocks 1357 +/- 507). Ultrasound stone diameter measurements were made pre- and post-BL; 12-wk results are reported. Treatment safety was assessed by recording adverse experiences and serum, urine, hematology, and chemistry. For patients with single stones, the high kV treatment took significantly (p < 0.05) less time (74 +/- 30 min) than moderate kV treatment (118 +/- 33 min). At 3 months, the moderate kV-treated single-stone group had a residual maximum fragment size of 3.2 +/- 3.3 mm versus 1.8 +/- 2.3 mm in the high kV-treated single-stone group. The 3-month stone-free rate for patients with single stones treated at high kV was 44% compared with 46% for the moderate kV-treated group (NS). At 1 wk, 11 patients had microscopic or macroscopic hematuria and six patients had mildly elevated liver function tests. At 6 wk, however, all urine and hematological measurements had returned to normal. Two patients suffered pancreatitis, one in each group. High kV BL appears to be safe and, for patients with single stones, gives better fragmentation and takes less time to administer than moderate kV. Whether a high kV treatment protocol can achieve improved long term stone-free rates remains to be assessed. PMID- 1449136 TI - Gastric and duodenal mucosal prostaglandin concentrations in gastric or duodenal ulcer disease: relationships with demographics, environmental, and histological factors, including Helicobacter pylori. AB - We measured gastric and duodenal mucosal prostaglandin concentrations in 69 patients with active or inactive duodenal or gastric ulcer disease and 26 non ulcer controls. Each underwent endoscopy enabling us to obtain multiple biopsies from the gastric body and antrum and from the duodenal bulb and postbulbar duodenum for measurement of mucosal prostaglandin concentrations, as well as a single biopsy from each region for mucosal histology. Using a multivariate linear regression model, we found that neither gastric nor duodenal ulcer disease significantly affected gastric or duodenal mucosal prostaglandin concentrations. Mucosal prostaglandin concentrations were similar at the edge of the ulcer and in the adjacent non-ulcerated mucosa. Neither gender symptoms, smoking, use of H2 receptor antagonists, disease activity, nor Helicobacter pylori infection had an independent effect on mucosal prostaglandins in any region. Gastritis in the body of the stomach was associated with significantly higher prostaglandins, while older age was associated with significantly lower gastric and duodenal prostaglandins. Gastroduodenal mucosal prostaglandins are thus not altered in patients with active or inactive peptic ulcer disease, even when multiple demographic and histologic variables are taken into consideration. PMID- 1449137 TI - Flexible sigmoidoscopy screening in an industrial setting. AB - Little is known about the yield of colorectal cancer screening programs in an industrial setting. We therefore established a flexible sigmoidoscopy screening program at a chemical manufacturing plant and offered testing to all employees over the age of 40. After a Fleet enema preparation had been administered, a digital rectal examination and sigmoidoscopy were performed on each volunteer worker in the medical office of the plant. The plant had an average census of about 650 workers; 202 were screened during a 2-yr period. The mean (+/- SEM) age of participants was 52 +/- 0.4. Sixty-four employees had polyps (31.7%); data on follow-up colonoscopy were available in 69%. Colonoscopy revealed adenomatous polyps in 23 workers (53.5%), hyperplastic polyps in 10 (23%), and no evidence of neoplasia in 10 (23%). Seven workers did not arrange for follow-up colonoscopy and 12 individuals could not be contacted. No cancers were detected. In the 40- to 50-yr age group, polyps were detected in 19.5% of employees (25% adenomatous). Incidental findings were common, and included prostatic nodules, hemorrhoids, diverticulosis, and proctitis, among others. We conclude that screening sigmoidoscopy can be conveniently and economically performed at the workplace, with a high yield and good worker acceptance. The high yield suggests a possible association between polyp formation and work in a chemical plant. The finding of adenomatous polyps in the younger patients suggests that the threshold for flexible sigmoidoscopy at age 50 needs to be reassessed. PMID- 1449138 TI - Gastrointestinal pneumocystosis in HIV-infected patients on aerosolized pentamidine: report of five cases and literature review. AB - Extrapulmonary infection with Pneumocystis carinii in AIDS patients on aerosolized pentamidine is occurring more frequently. We report five patients diagnosed with gastrointestinal pneumocystosis while on aerosolized pentamidine prophylaxis and have identified infections involving the peritoneum, liver, and transverse colon, as well as stomach and duodenum. Physicians should have a high index of suspicion for extrapulmonary pneumocystosis, especially involving the gastrointestinal system, in HIV-infected patients, and early diagnosis must be pursued aggressively. The use of aerosolized pentamidine as prophylaxis for P. carinii pneumonia is not protective against gastrointestinal pneumocystosis because of inadequate systemic distribution of the drug. To our knowledge, this is the first report in a clinical journal documenting and photographing P. carinii organisms in ascitic fluid. PMID- 1449139 TI - Clinical, endoscopic, immunologic, and therapeutic aspects of oropharyngeal and esophageal candidiasis in HIV-infected patients: a survey of 114 cases. AB - The medical records of 114 consecutive HIV-infected patients with oropharyngeal and esophageal candidiasis, in whom esophagoscopy was performed, were reviewed. Esophageal candidiasis and isolated oral candidiasis were found in 75% and 25% of patients, respectively. Esophageal candidiasis was the AIDS-defining illness in 65 patients and dysphagia was the commonest symptom, but asymptomatic Candida esophagitis was observed in 43% of them. Symptoms were present in six patients with oropharyngeal candidiasis; three of them had a normal esophagoscopy and the other three had acute nonfungal esophagitis. Invasive fungal esophagitis was confirmed by biopsy in 47/74 patients (64%). The patients with esophageal candidiasis had lower CD4+ cell counts (129/microliter) and CD4:CD8 ratios (0.23) than those with oropharyngeal candidiasis (CD4 179/microliter; CD4:CD8 0.35). Thirty-six patients with esophageal candidiasis were treated with fluconazole, 100 mg/daily, for 28 days, and another 34 patients received the same dose for 10 days. A similar efficacy was seen in both regimens, but a higher incidence of oropharyngeal fungal colonization and liver dysfunction was observed in the longer therapy (p < 0.001). We conclude that asymptomatic C. esophagitis is common in HIV-infected patients. Patients with oropharyngeal candidiasis may complain of esophageal symptoms; it could be due to superficial C. infection or another not-identified opportunistic infection. More severe immunologic impairment was required to develop esophageal candidiasis than oropharyngeal candidiasis. A short course of 10 days of fluconazole therapy could be the standard regimen for the treatment of C. esophagitis in AIDS. PMID- 1449140 TI - Gastric acid secretion in HIV-1 infection. AB - It has been suggested that AIDS patients may have reduced gastric acid output. This is of concern because gastric acid may be required for absorption of oral antifungal agents that are important in AIDS management. The cause as well as the progression of reduced gastric acid output in AIDS patients is unclear. This study investigated gastric acid output in relation to the stage of non-AIDS HIV-1 infected patients. No statistical difference was found between nine control and 26 male HIV-infected subjects in basal acid output, maximal acid output, peak acid output, or fasting serum gastrin, regardless of stage. Likewise, no relationship between stage of HIV infection and gastric acid output was determined. We conclude that there is no impairment in basal and maximally stimulated gastric acid secretion in non-AIDS HIV-1-infected males. In addition, the clinical stage of non-AIDS HIV-1 infection has no effect on gastric acid secretion. PMID- 1449141 TI - Decreased intrinsic factor secretion in AIDS: relation to parietal cell acid secretory capacity and vitamin B12 malabsorption. AB - AIDS-associated gastric secretory failure has been characterized by decreased secretion of acid, pepsin, and gastric juice volume. To determine whether decreased intrinsic factor secretion and vitamin B12 malabsorption occur in this entity, we performed prospective measurements of maximal acid output, intrinsic factor output, vitamin B12 absorption, serum vitamin B12, and holotranscobalamin II in 10 consecutive AIDS patients. Four of 10 patients had low maximal acid output, i.e., < or = 1.5 mEq/h (control = 12.8 +/- 9.0, range 2.5-25 mEq/h). Four patients had low intrinsic factor output, i.e., < or = 1.1 microgram/h (control = 8.2 +/- 6.9, range 3.1-19.4 micrograms/h). One patient with low intrinsic factor output had low serum vitamin B12 and a Schilling test consistent with pernicious anemia. A second patient with very low intrinsic factor output (0.16 micrograms/h) had low parts I and II Schilling tests; malabsorption most likely resulted from both low intrinsic factor secretion and ileal disease. One of three vitamin B12 malabsorbing patients, with normal serum vitamin B12, had low holotranscobalamin II, 25 pg/ml (control holotranscobalamin II = 76 +/- 44, range 44-152 pg/ml). Maximal acid output and intrinsic factor output did not correlate in AIDS (r = 0.36, p = 0.30) in contrast to the expected correlation in controls (r = 0.91, p = 0.03). We conclude that low intrinsic factor secretion is common in AIDS and contributes to vitamin B12 malabsorption. Decreased parietal cell secretion of intrinsic factor and acid may occur independently in human immunodeficiency virus-associated gastric secretory failure. Low holotranscobalamin II, an early manifestation of vitamin B12 malabsorption, results in decreased delivery to vitamin B12-dependent tissues prior to depletion of serum vitamin B12. Regular supplementation with vitamin B12 may therefore be warranted in patients with advanced HIV infection. PMID- 1449142 TI - Treatment of intractable hiccup with baclofen: results of a double-blind randomized, controlled, cross-over study. AB - Four patients with intractable hiccup were treated in a double-blind, randomized, placebo, cross-over study with an analogue of gamma-aminobutyric acid, Baclofen. There was a consistent and statistically significant (p = 0.03) improvement in hiccup severity with Baclofen, both subjectively (p = 0.03) and by hiccup-free periods (p = 0.003). The actual frequency of hiccup was not significantly altered by the medication. We propose that the mechanical aspects of hiccup are reduced by Baclofen, leading to a perceptual blockage and a decrease in the reflex severity induced by the gamma-aminobutyric acid analogue. We conclude that this medication may be useful for the treatment of intractable hiccup. PMID- 1449143 TI - Prognostic factors of hepatic encephalopathy after portacaval anastomosis: a multivariate analysis in 50 patients. AB - Portacaval anastomosis has proved to be effective in avoiding active and recurrent hemorrhage from gastroesophageal varices in liver cirrhosis. However, hepatic encephalopathy is the most common and serious complication of this procedure. The aim of this study was to investigate by multivariate analysis the predictive factors of development of hepatic encephalopathy in 50 Child's A and B cirrhotic patients whose variceal bleeding was treated with emergency (n = 17) or elective (n = 33) portacaval anastomosis. The etiology of the cirrhosis was alcoholic in 74% of cases. The mean follow-up was 22.7 +/- 16.6 months (range 1 60 months). The 2-yr probability of suffering from at least one episode of hepatic encephalopathy in the overall group was 43%. The multivariate analyses (Cox's regression method) of 37 variables based upon clinical history, physical examination, and laboratory data disclosed that only five of these variables had independent predictive value: need for diuretic treatment in the days prior to surgery, absence of hepatomegaly, and serum levels of total bilirubin, gamma globulin, and hemoglobin. According to the contribution of each one of these factors to the final model, a prognostic index was obtained which allowed the division of patients in two different groups of risk for developing hepatic encephalopathy (20% and 74%, respectively, after 2 yr of surgery; p = 0.0002). This index may help to better choose those candidates for portacaval anastomosis. PMID- 1449144 TI - Endoscopic sclerotherapy: treatment of choice in patients less than 3 years old with extrahepatic portal vein obstruction. AB - Thirty-two children under 3 yr of age with extrahepatic portal vein obstruction were treated with endoscopic sclerotherapy. The group consisted of 22 males and 10 females, with a mean age of 1.96 yr (range 7 months to 3 yr). The procedure was well tolerated by all after premedication with intravenous diazepam. Esophageal varices were eradicated in all children after 4.45 sessions (+/- 1.12). Follow-up clinical and endoscopic evaluations have been carried out over a period of 9 months to 4 yr (mean 3.5 yr) after the patients were put on a sclerotherapy program. There was a significant reduction in number of bleeding episodes (60 vs. 8), mean blood transfusion requirement (2.19 vs. 0.31), and bleeding risk factor (0.09 vs. 0.008). There were a few minor conditions, such as transient dysphagia and esophageal ulcerations, in 14 patients (43.75%), which later responded to medical treatment. Perisclerotherapy bleeding, seen in six patients (18.7%), responded to repeat sclerotherapy. Recurrence of varices was encountered in two patients (6.25%); these were eradicated after reinstitution of sclerotherapy. Endoscopic sclerotherapy is the treatment of choice in patients of extrahepatic portal vein obstruction who are below 3 yr of age. PMID- 1449145 TI - Bile duct varices or "pseudo-cholangiocarcinoma sign" in portal hypertension due to cavernous transformation of the portal vein. AB - A total of 832 patients with portal hypertension resulting from different etiology was studied by ultrasonograph as a screening test. In 17 of the 832 patients, cavernous transformation of the portal vein was detected by means of ultrasonography. We have prospectively studied these 17 patients, and the diagnosis of cavernous transformation was confirmed by portography in all patients. To evaluate how much biliary tract has been affected from cavernous transformation of the portal vein, and to explain the cause of mildly increased alkaline phosphatase and serum bilirubin levels, endoscopic retrograde cholangiopancreatography (ERCP) was performed in 16 of the 17 patients. There were narrowing, irregularity, undulation and nodular extrinsic defects resulting from compression of thrombosis of the portal vein and the collateral vessels, mimicking cholangiocarcinoma spreading along the common bile duct on the extrahepatic biliary tract in all 16 patients who underwent ERCP. Similar ERCP findings were not found in six patients with portal hypertension due to liver cirrhosis. The ultrasonographic, portographic, and ERCP findings corresponded to surgical findings in six patients who had undergone splenectomy for either hypersplenism or bleeding from esophageal varices. The results indicate that cavernous transformation of the portal vein cause the above-mentioned radiographic findings that we propose to call "pseudo-cholangiocarcinoma sign." PMID- 1449146 TI - Factors influencing acceptance of hepatitis B vaccination by hospital personnel in an area hyperendemic for hepatitis B. AB - A free-of-charge vaccination program against hepatitis B, in which plasma-derived vaccine was used, was offered to 1,299 hospital personnel of Chulalongkorn University Hospital, Bangkok. The initial acceptance rate for vaccination was 65.7%, with 10.0% nonacceptance and 24.3% undecided. The highest rates of acceptance were among medical students (75.5%), student nurses (68.8%), and newly graduated nurses (63.6%). The lowest rate of acceptance was among physicians (48.2%). Factors strongly associated with the acceptance of vaccination were nature of work, age of personnel (< or = 40 yr), number of years spent in profession (< or = 15 yr), knowledge of hepatitis B, confidence in vaccine efficacy and safety, no history of hepatitis B infection, and contact with blood or blood product. Different types of fear, as well as lack of knowledge, were the main reasons responsible for 46.2% of all refusals. More specific educational efforts about vaccine safety and efficacy may positively influence the acceptance of hepatitis vaccination program among health care personnel. PMID- 1449147 TI - Can cytokines prolong survival in ampullary neuroendocrine carcinomas? AB - Herein we report the case of an ampullary tumor in a 53-yr-old Japanese woman who presented in March 1988 with abdominal pain, weight loss, and jaundice. A pancreatoduodenectomy was carried out, and 3 months later, she presented with a Virchow's node. She was initially treated with cytokines plus 5-fluorouracil derivative, resulting in a complete remission lasting over a year. However, in July 1990, the Virchow's node reappeared and was surgically excised. Histology revealed a small-cell neuroendocrine carcinoma (SCNC) similar to the prior ampullary tumor, which was confirmed by immunohistochemical studies and electron microscopic examination. The patient was discharged within 1 month, remaining disease-free over a 18-month period following excision. We suggest that the use of cytokines can be effective, and can increase survival in gastrointestinal neuroendocrine tumors. PMID- 1449148 TI - Familial multiple congenital esophageal rings: report of an affected father and son. AB - Multiple esophageal rings are a very unusual cause of dysphagia. We report a case of a 35-yr-old male with multiple esophageal rings and severe dysphagia, whose father had similar symptoms. Our patient underwent esophageal dilation on one occasion and is asymptomatic at 1-yr followup. We speculate that multiple esophageal rings may be of congenital origin. PMID- 1449149 TI - Antibiotic-associated fulminant pseudomembranous colitis without toxic megacolon. AB - Presented is a middle-aged male who developed a fulminant case of antibiotic associated pseudomembranous colitis characterized by leukocytosis, hypoalbuminemia, ascites, and anasarca without toxic megacolon. The patient responded slowly to medical therapy consisting of intravenous metronidazole, oral vancomycin, and parenteral nutrition. Subsequently, cholestyramine was administered. A review of the literature concerning similar cases of fulminant pseudomembranous colitis is presented. PMID- 1449150 TI - Syphilitic gastritis in an HIV-infected individual. AB - We report the first known case of syphilitic gastritis in an HIV-infected person. The presentation of nonspecific abdominal pain and weight loss in a 48-yr-old former intravenous drug user previously treated for asymptomatic syphilis led to a barium swallow which demonstrated linitis plastica. Upper endoscopy reinforced a suspicion of carcinoma, but biopsy made the diagnosis of syphilis by silver staining. Further testing revealed a positive serology for syphilis as well as HIV infection with a depressed CD-4 lymphocyte count. Treatment with parenteral penicillin led to a rapid resolution of symptoms. This case represents a rare complication of late syphilis, and is another example of the unusual manifestations of syphilis seen in the HIV-infected population. PMID- 1449151 TI - Gastrointestinal obstruction due to Mycobacterium avium intracellulare associated with the acquired immunodeficiency syndrome. AB - Three patients with the acquired immunodeficiency syndrome (AIDS) had complete or incomplete gastrointestinal obstruction resulting from infection with Mycobacterium avium intracellulare. The pathophysiologic mechanisms of the obstruction in the three cases were ileal volvulus due to adhesions from matted infected mesenteric lymph nodes, ileal intussusception due to engorged infected ileal mucosa, and small bowel displacement and compression by massively enlarged infected intraabdominal lymph nodes. These reports extend the clinical manifestations of Mycobacterium avium intracellulare infection in patients with AIDS to include partial and complete gastrointestinal obstruction. PMID- 1449152 TI - Arterioportal fistula: a role for pre-TIPSS arteriography and hepatic venous pressure measurements. AB - A 70-yr-old male presented with massive upper gastrointestinal bleeding secondary to esophageal varices. Because the bleeding was not controlled by sclerotherapy or vasopressin and nitroglycerin, the patient was evaluated for a transjugular intrahepatic portosystemic shunt. Preprocedure arteriography was performed because the etiology of the portal hypertension was uncertain. The arteriogram revealed a hepatic artery to portal vein fistula. Hepatic venous pressure measurements documented an elevated hepatic venous pressure gradient, which diminished dramatically upon embolization of the fistula. Rebleeding from the varices was associated with reestablishment of the fistula via collaterals and elevation of the hepatic venous pressure gradient. The case is presented to establish a role for arteriography prior to transjugular intrahepatic portosystemic shunting, especially in patients with unexplained portal hypertension, and to establish the potential value of hepatic venous pressure measurements in the treatment of arterioportal fistulas. PMID- 1449153 TI - Delayed massive hemobilia following percutaneous liver biopsy: treatment by embolotherapy. AB - A patient developed delayed life-threatening hemobilia after apparently uncomplicated percutaneous needle liver biopsy. An arteriobiliary fistula demonstrated by arteriography was successfully treated by selective transcatheter arterial embolization, with Gelfoam and a Gianturco coil. The diagnosis of liver biopsy-induced hemobilia should be suspected when a postprocedure fall in hematocrit is associated with abdominal pain, hyperbilirubinemia, or unexplained gastrointestinal bleeding. A review of the diagnosis and management of liver biopsy-related hemobilia is presented. PMID- 1449154 TI - Listeria monocytogenes peritonitis: case report and literature review. AB - Listeria monocytogenes is a Gram-positive bacillus that is pathogenic in both the normal and compromised host. We describe Listeria peritonitis and cerebritis in a patient with cirrhosis due to non-A, non-B hepatitis, and review the 11 other cases of Listeria peritonitis reported in the English-language literature. Listeria is a rare cause of peritonitis in debilitated, older patients, with two thirds of the cases occurring in patients with chronic liver disease. Listeria peritonitis may also occur in patients undergoing peritoneal dialysis, or in those with malignancy. Peritonitis due to Listeria is clinically similar to spontaneous bacterial peritonitis, and is associated with fever, variable abdominal pain, and neutrocytic ascites; bacteremia commonly accompanies Listeria peritonitis. This syndrome can be successfully treated with antimicrobial drugs, although the third-generation cephalosporins commonly used in the therapy of spontaneous bacterial peritonitis are not recommended. Ampicillin may be the drug of choice, with combination therapy with an aminoglycoside reserved for cases that do not respond to ampicillin alone. PMID- 1449155 TI - Enterolith ileus: a rare complication of duodenal diverticula. AB - Small bowel obstruction secondary to an enterolith formed within a duodenal diverticulum is a rare complication. Twenty-nine cases of enterolith ileus have been reported in the literature. This is a case report of the 30th, with review of the literature. Enterolith ileus closely resembles gallstone ileus in its clinical presentation. Diagnosis is established by documenting normalcy of gallbladder and the presence of small bowel diverticula. PMID- 1449156 TI - Post-cholecystectomy diarrhea: evidence of bile acid malabsorption assessed by SeHCAT test. AB - Although bile acid malabsorption (BAM) in post-cholecystectomy diarrhea (PCD) is a well-known clinical condition, its true etiopathogenetic role is not entirely clear. The SeHCAT (23-selena-25-homotaurocholic acid) test, a simple and reliable BAM test, was performed in 33 cholecystectomized patients, 26 with chronic diarrhea. The test revealed a marked degree of BAM in 25/26 cases. Cholestyramine in doses of 2-12 g/day was effective in 23/25, ineffective in two, and was not tolerated in one patient. When treatment was suspended, diarrhea recurred in nine, whereas bowel habit remained regular in 60%, with brief sporadic episodes of diarrhea in the other cases. The SeHCAT test was repeated in 11 cases after cholestyramine treatment interruption, and revealed the normalization of parameters in two patients and an improvement in three. We conclude that BAM is an important etiopathogenetic factor in PCD that responds favorably to cholestyramine. In 60% of the cases, it resolved diarrhea definitively, although without eliminating BAM in all cases: this suggests that existence of other factors associated with BAM. The SeHCAT test is essential for a differential diagnosis between PCD and the irritable bowel syndrome. PMID- 1449157 TI - Marked hyperlipidemia and pancreatitis associated with isotretinoin therapy. AB - Isotretinoin, a retinoid derivative, is in wide use as a treatment for severe acne and other dermatologic conditions. Its effects on serum lipids, most notably the induction of hypertriglyceridemia, have been well documented. We present a case of a young woman with a previous history of gestational hyperlipidemia who developed hypertriglyceridemia and pancreatitis after initiation of isotretinoin therapy. A history of gestational hyperlipidemia may serve as a marker to help identify patients who are at increased risk for developing severe hypertriglyceridemia while receiving isotretinoin. Her case emphasizes the need to consider the possibility of pancreatitis in patients who develop abdominal pain while receiving this drug. PMID- 1449158 TI - Multiple hemangiopericytomas of the spleen. AB - Splenic tumors are uncommon. Described is a 58-yr-old man with multiple hemangiopericytomas of the spleen. Hemangiopericytoma is categorized as a benign vascular tumor, but has a relatively high malignant potential. A review of the literature shows that the case we present is only the second ever reported of a tumor originating from the spleen. Radiological findings and the treatment of the tumor are discussed. PMID- 1449159 TI - Common bile duct obstruction due to pancreatic involvement in the von Hippel Lindau syndrome. AB - Pancreatic involvement in the von Hippel-Lindau syndrome occurs frequently, but is nearly always asymptomatic. Until now, only two cases of bile duct obstruction as a complication of this syndrome have been reported. We present another report of cholestatic jaundice in a patient with the von Hippel-Lindau syndrome and multiple pancreatic cystic lesions, treated by endoscopic implantation of a biliary stent. PMID- 1449160 TI - Accredited fellowship training programs in gastroenterology. PMID- 1449161 TI - Beta-blockers and prevention of first variceal hemorrhage: tantalizing expectations? PMID- 1449162 TI - Hepatitis B and renal transplantation: dangling the sword of damocles? PMID- 1449163 TI - Steroids in alcohol hepatitis: hope or hype? PMID- 1449164 TI - Colonic metabolism of short-chain fatty acids. PMID- 1449165 TI - Hepatotoxicity of 6-mercaptopurine in Crohn's disease. PMID- 1449166 TI - Bleeding anal varix: adverse effects of local treatment with histoacryl. PMID- 1449167 TI - Advantage of use of DPM for 14C-urea breath test for the detection of Helicobacter pylori. PMID- 1449168 TI - Pancreatitis after endoscopic cholangiography without pancreatography. PMID- 1449169 TI - Ultrasonic assessment of inflammatory bowel disease. PMID- 1449170 TI - Aeromonas sobria spontaneous bacterial peritonitis. PMID- 1449171 TI - A new chemotherapy against pseudomyxoma peritonei. PMID- 1449172 TI - Lipohyperplasia of the ileocecal valve contiguous with adenocarcinoma of the gallbladder. PMID- 1449173 TI - Cerumen management. PMID- 1449174 TI - Anatomic importance of the retrofacial air tract. AB - The retrofacial air tract is a constant and relevant anatomic landmark for the temporal bone surgeon. By purposefully dissecting this space, one is able to safely identify the facial nerve, endolymphatic sac, and jugular bulb. The retrofacial air tract also provides access to the petrous apex. Forty temporal bones of varying degrees of pneumatization were dissected in order to study the retrofacial air tract. A well-developed air tract was easily identified in all specimens. We describe our anatomic findings and discuss the surgical relevance and important of the retrofacial air tract. PMID- 1449175 TI - Binaural cochlear implants. AB - With the success of monaural cochlear implantation, patients frequently ask about having a second implant. We have performed binaural cochlear implants in 12 adult patients. Desire not to disrupt a functioning implant was the primary consideration in implanting the contralateral ear. Seven patients received a second 3M/House single-channel implant to upgrade to a magnetic external receiver. Four patients with a 3M/House device in one ear elected to place a Nucleus multichannel implant in the opposite ear. One patient with a poorly functioning Nucleus device elected to have a second Nucleus device. Four patients with a Nucleus and a 3M/House implant, one with binaural 3M/House implants, and one with binaural Nucleus implants were tested for auditory discrimination in order to quantify monaural versus binaural differences. The functional benefit of the second implant was mixed, but all patients showed some degree of objective improvement on one or more tests. Five of the six are regular users of both devices; the patient with binaural Nucleus implants wears only one. Despite the differing processing schemes, patients with a Nucleus device in one ear and a 3M/House device in the other ear are able to combine the two signals to advantage. We feel that cochlear implantation in the contralateral ear is an acceptable option in selected patients desiring an upgraded implant without placing a functioning implant at risk. PMID- 1449176 TI - Macrothrombocytopenia and progressive deafness: a new genetic syndrome. AB - We report a kindred with hereditary macrothrombocytopenia and progressive sensorineural hearing loss. Although the occurrence of hereditary sensorineural hearing loss associated with macrothrombocytopenia has been reported in a small number of families, varying degrees of renal pathology have always been present. In contrast to the previously reported syndromes involving a giant-platelet disorder and deafness, none of the family members in this report have had any evidence of renal dysfunction. The disorder was inherited in a linear pattern from great-grandmother to grandmother to mother to daughter. The clinical manifestations include hearing impairment that begins before the third decade and progresses to severe to profound bilateral hearing loss by the fourth decade. The platelet disorder manifests in early childhood and persists lifelong, although it tends to remain subclinical. Hematologic and ultrastructural findings will be contrasted to those found in Alport syndrome. PMID- 1449177 TI - Luetic endolymphatic hydrops: diagnosis and treatment. AB - Luetic endolymphatic hydrops (LEH) is an effectively treatable disorder that requires astute clinical judgment to suspect, confirm, and treat. We provide a review of the literature as well as recommendations regarding the clinical management of LEH with discussion of several illustrative cases. We also give an overview of laboratory testing for the diagnosis and monitoring of the infectious process. Ultimately, the control of the otologic symptoms in LEH requires acumen on the part of the clinician. PMID- 1449178 TI - Cochlear implants in the management of bilateral acoustic neuromas. AB - Multichannel cochlear implants currently provide the only modality for successful auditory rehabilitation of patients with bilateral profound sensorineural hearing loss who derive no benefit from amplification. We have developed a protocol for patients with neurofibromatosis and bilateral acoustic neuromas in which every effort is made to preserve hearing in at least one ear. Failing that, the cochlear nerve is spared, potentially allowing for the insertion of a cochlear implant. We present our data on one such patient whose auditory function was restored with a Nucleus mini 22-channel cochlear implant following removal of his acoustic neuroma. PMID- 1449179 TI - Evaluation of perilymphatic fistulas by middle ear endoscopy. AB - Transtympanic endoscopy provides a unique opportunity to view the undisturbed contents of the middle ear. Fiberoptic and rigid endoscopes have been used for thorough examination of the middle ear without the need for local anesthetics or surgical trauma. Endoscopy is now routinely used in the evaluation of a perilymphatic fistula and the patient is awake during an intermittent forceful Valsalva maneuver. Oval and round windows in both ears of five cats were studied endoscopically to evaluate surgically created fistulas. Excellent visualization of the defect was obtained in all instances. Endoscopy is a useful office technique for the evaluation of perilymphatic fistula. It reduces the need for surgical exploration and provides a satisfactory examination of the middle ear. Obliteration of the window niche can even be performed through the myringotomy using autologous blood. PMID- 1449180 TI - Spontaneous temporal bone cerebrospinal fluid leak. AB - Eight patients with spontaneous cerebrospinal fluid leak of temporal bone origin are presented. Pertinent history and surgical findings are reviewed and contrasted with 33 previously reported patients. Unilateral ear fullness and mild hearing loss are the most common presenting symptoms. Profuse clear otorrhea following myringotomy is virtually pathognomonic. Diagnostic methods including high-resolution computed tomography, magnetic resonance imaging, and contrast cisternography are discussed. The indications for transmastoid and combined transmastoid/middle fossa surgical repairs are compared. Both surgical approaches were found to be equally effective. We favor the transmastoid as the initial approach because of simplicity, safety, and the ability to visualize both the middle fossa and posterior fossa plates as well as the middle ear. PMID- 1449181 TI - Autologous fibrin tissue adhesive for ossicular reconstruction in cats. AB - Autologous fibrin tissue adhesive is currently the most promising adhesive for otologic use with respect to strength and biocompatibility without the risk of transmissable disease that is of concern with the commercially prepared fibrin adhesive. We set out to evaluate the practicality of preparing autologous fibrin adhesive in cats and to see if the adhesive's duration and strength of bonding was sufficient to allow natural tissue union to occur with various grafting materials. Autologous fibrin adhesive was prepared preoperatively from ten cats using the ammonium sulfate precipitation technique. Twenty otologic procedures were performed in which the incus long process was resected and the defect bridged with one of four grafting materials: autograft ossicular bone, bone pate fibrin glue, porous hydroxylapatite, and Plastipore-bone pate. All grafts were secured with the autologous adhesive. The cats were sacrificed at 6 and 12 weeks. We found the the autologous adhesive provided adequate duration and strength of support to enable a firm tissue union between all the grafting materials and the adjoining incus and stapes. PMID- 1449182 TI - Ossiculoplasty prognosis: the spite method of assessment. AB - A series of 535 ossiculoplasties were studied to determine statistically significant links between the presence of presenting preoperative clinical features and adverse audiologic results, in order to identify those aspects of case presentation that indicate a good or poor prognosis. Analysis by chi-square testing has identified twelve features classified as surgical, prosthetic, infection, tissue, and eustachian (SPITE) factors. Regrouping the significant features has demonstrated their value in predicting accurately an ossiculoplasty prognosis. The data were used to compare accurately the results of 247 Plastipore procedures and 265 procedures using the Richards Oval-Top hydroxylapatite implant. There was no statistical difference between the series. The use of these factors will permit precise matching of future series to allow accurate comparisons of prostheses, techniques, individual skills, and also surgical philosophies such as the open and closed cholesteatoma management. Most importantly, the SPITE factors permit an accurate preoperative individual assessment when counseling the patient as to the likelihood of success or failure of a proposed ossiculoplasty. PMID- 1449183 TI - Beta 2 transferrin application in otology. AB - The diagnosis and management of perilymphatic fistula has received considerable attention in recent years. Despite the use of sophisticated technology, the diagnosis of perilymphatic fistula continues to rest primarily upon clinical suspicion and the exclusion of other disorders. In addition, the confirmation of a perilymphatic fistula during surgical exploration is usually based upon the subjective observation of fluid pooling in niches of the middle ear. A sensitive and objective laboratory test for identifying perilymph in the middle ear would be a useful adjunct for the diagnosis and management of perilymphatic fistula. The objective of this paper is to demonstrate the potential utility of beta 2 (beta 2) transferrin assay in the diagnosis of perilymphatic fistula. To accomplish this objective, we confirmed that beta 2 transferrin is present in living human perilymph and is absent in the normal or inflamed middle ear. In addition, the utility of beta 2 transferrin assay in the diagnosis of cerebrospinal fluid otorrhea is presented. PMID- 1449184 TI - Argon laser stapedectomy: comparison to traditional fenestration techniques. AB - A retrospective review of all stapedectomies performed at the Massachusetts Eye and Ear Infirmary over a 13 month period was undertaken to compare the results of argon laser stapedectomy to conventional footplate fenestration techniques. Despite the fact that it was new and unfamiliar to the surgical staff, the complication rate was lower with the argon laser than with footplate fenestration by traditional pick or drill techniques. The incidence of footplate fracture or removal preventing use of a small fenestra technique was five times as likely to occur with traditional instruments as with the argon laser (p < 0.025). In revision stapedectomy sensorineural hearing loss was four times as likely to occur with traditional instruments as with the argon laser (p < or = 0.05). The argon laser did not alter the operating time. Though not ideal for every case, the argon laser endo-otoprobe offers the surgeon a significant new tool to improve the outcome in stapes surgery. PMID- 1449185 TI - Radiographic differential diagnosis of petrous apex lesions. AB - As a consequence of improved diagnostic imaging modalities, otologists have encountered a steadily increasing number of petrous apex lesions in recent years. Contemporary imaging techniques not only provide precise anatomic localization of the lesion, but also are able to suggest specific tissue diagnoses in the majority of cases. Computed tomography (CT), by virtue of its sensitivity and low false-positive rate, is the screening examination of choice in a patient suspected of having a petrous apex lesion. Once a lesion is identified, it is often necessary to obtain a combination of CT and magnetic resonance imaging (MRI). Computed tomography is important in the detection of osseous erosion as well as in the evaluation of the extent of pneumatization and marrow formation. It also provides important details about potential surgical routes to this relatively inaccessible region. Magnetic resonance imaging provides information about the composition of the lesion that cannot be readily discerned on CT scans. In the great majority of cases, it is capable of differentiating between petrous apicitis, cholesterol granuloma, osteomyelitis, cholesteatoma, and neoplasms such as schwannoma, meningioma, chondroma, and chordoma. In the interpretation of MRI scans, a familiarity with the typical appearance of the lesions that affect the petrous apex on T1-weighted, T2-weighted, and gadolinium-enhanced images is essential. A combination of MRI and CT scanning is also necessary to evaluate normal anatomic variations, such as giant air cells and asymmetric bone marrow, which may at times, on MRI alone, simulate pathologic conditions. PMID- 1449186 TI - Immune-mediated inner ear disease. AB - Recent clinical studies, experimental research, and various testing techniques in otoimmunology have resulted in presentation of the synonymous terms autoimmune sensorineural hearing loss, autoimmune inner ear disease, immune-mediated sensorineural hearing loss, and immune-mediated inner ear disease or disorder. The development of this terminology and the clinical presentation of this disease as well as whether it is really a distinct clinical entity are discussed. Laboratory tests for immune-mediated inner ear disease are presented along with a discussion of progress being made in the growing field of otoimmunology. PMID- 1449187 TI - Dermoid tumor of the middle ear: case report and literature review. AB - Dermoids and teratomas are frequently described in the head and neck, but are rarely found in the middle ear or temporal bone. We have recently managed a case of an extensive middle ear dermoid occurring in a 14-month-old female. The purpose of this article is to report the presentation and management of this case and to review the literature with respect to this entity. PMID- 1449188 TI - Blastomycotic cranial osteomyelitis. AB - This is the second case report of a temporal bone osteomyelitis caused by Blastomyces dermatitidis, which presented as a chronic serous otitis media. The presenting serous otitis media was refractory to conventional medical and surgical management and progressed to a temporal bone osteomyelitis prior to diagnosis. B. dermatitidis is a rare fungal pathogen that causes a systemic pyogranulomatous disease that primarily manifests itself in the skin, bones, pulmonary, and genitourinary systems. If left untreated it is associated with a high rate of mortality. The otologic presentation of this rare disease is emphasized, while the clinical and therapeutic features are reviewed. PMID- 1449189 TI - Facial and trigeminal neural dysfunction by a primary cutaneous squamous cell carcinoma: MRI and clinicopathologic correlates. AB - Carcinomatous neural infiltration and subsequent neural dysfunction are phenomena associated with the facial nerve and parotid gland tumors, particularly adenoid cystic carcinoma. The association of primary cutaneous squamous cell carcinoma (PCSCC) with these phenomena is not as well recognized, especially with respect to the involvement of the trigeminal nerve. By presenting the case history of a man who successively developed facial and trigeminal neural dysfunction after Mohs chemosurgery of a PCSCC, this paper documents histologically the occurrence of such neural invasion, and illustrates the utility of gadolinium-enhanced magnetic resonance scanning in patient management. PMID- 1449190 TI - Contemporary diagnostic update: clinical utility of computerized oculomotor and posture testing. PMID- 1449191 TI - Value of human temporal bone studies in advancing the understanding of diseases of the ear. PMID- 1449192 TI - Hearing results following posterior semicircular canal injury during antesigmoid retrolabyrinthine selective vestibular nerve section. AB - The disastrous hearing results in six patients whose posterior semicircular canal was entered during antesigmoid mastoid craniotomy for retrolabyrinthine selective vestibular nerve section were reviewed. The injury occurred during skeletonization of the posterior semicircular canal to maximize intracranial exposure of the eighth nerve. All patients had Meniere's disease. Four patients were deafened, and in two, there was either no serviceable hearing or severe hearing impairment in the operated ear. Caution is urged in posterior semicircular canal labyrinthotomy for vertigo and attempted hearing preservation if a patient has symptoms of endolymphatic hydrops. PMID- 1449193 TI - Mobilization strategy for guinea worm eradication in Nigeria. AB - The transformation of dracunculiasis from an obscure and neglected rural disease to the highly visible target of a national eradication campaign in Nigeria is described in this report. This process progressed through four overlapping stages: documentation of the extent and nature of the disease as a national problem, demonstration in Nigeria that dracunculiasis could be effectively prevented by targeted provision and use of protected rural water supplies, mobilization for community participation in, and political support of, the eradication effort, and implementation of interventions nationwide. The conduct of the first national village-by-village search for cases and documentation of the adverse socioeconomic impact of the disease (e.g., on rice production) in Nigeria were the key elements used to solicit greater attention to the problem and mobilize support for its eradication. The critical role of the mass media in this effort and other benefits of this mobilization strategy are also highlighted. PMID- 1449194 TI - The epidemiology of Chagas' disease in a hyperendemic area of Cochabamba, Bolivia: a clinical study including electrocardiography, seroreactivity to Trypanosoma cruzi, xenodiagnosis, and domiciliary triatomine distribution. AB - A clinicoepidemiologic survey of Chagas' disease was conducted in the remote rural village of Tabacal in southcentral Cochabamba, Bolivia. In June and July 1988, we interviewed and examined 153 of 160 villagers > five years old for signs and symptoms of Chagas' disease. All participants had electrocardiograms (EKGs) and serologic analysis performed, and 20 villagers underwent xenodiagnosis. All 40 houses in the village were examined for triatomes, and house construction materials and defects were recorded. Seventy-four percent of all villagers had serologic evidence of Chagas' disease, and were defined as cases. Cases were three and one-half times more likely to have signs and symptoms of heart failure than non-cases (P = 0.2) and were nine times more likely to have EKG conduction abnormalities than non-cases (P = 0.02). Thirty-three percent of all EKG conduction defects occurred in individuals < 35 years of age. All dwellings had evidence of triatome infestation; 72% of the triatomes collected were positive for metacyclic trypanosomes. We conclude that Trypanosoma cruzi infection is highly prevalent in Tabacal and is a common cause of morbidity in that region. PMID- 1449195 TI - Malaria transmission at a new irrigation project in Sri Lanka: the emergence of Anopheles annularis as a major vector. AB - Malaria transmission was studied in a newly irrigated area of the Mahaweli project in the dry zone of Sri Lanka. Observations were performed for a three month period following the northeast monsoon. Parasitemia in the population varied from 20.2% in February to 7% in May, and infection was due to both Plasmodium falciparum and P. vivax. Night catches of mosquitoes collected with human bait included a high proportion of Anopheles annularis. Mosquitoes containing sporozoites in the salivary glands were identified by an enzyme-linked immunosorbent assay. Anopheles culicifacies, An. annularis, and An. aconitus were all implicated as vectors in the area. The highest entomologic inoculation rate, 0.12 infected bites/hr, was observed with An. annularis and P. vivax in March. We suggest that a change in the ecosystem from dry zone forest to irrigated cultivated land is the cause of the increased prevalence of An. annularis in this area and its emergence as a major vector of malaria. PMID- 1449196 TI - Seroepidemiologic studies of humoral immune response to the Plasmodium falciparum antigens in Thailand. AB - We have investigated seroreactivity against Plasmodium falciparum crude parasite antigens, the P. falciparum ring-infected erythrocyte surface antigen (Pf155/RESA), as well as against two synthetic peptides (EENV)6 and (EENVEHDA)3 that represent important epitopes of Pf155/RESA. The study population consisted of 421 children and adult Thais living in an area with moderate malaria transmission. We related these serologic findings to some important epidemiologic baseline data collected in the study area. The parasite rate in study subjects was 18.76%. Sixty-two percent were seropositive to crude P. falciparum antigens, 30.3% to the Pf155/RESA antigen, 23.05% to (EENV)6, and 20.17% to (EENVEHDA)3. Antibody responses to crude P. falciparum antigens and to Pf155/RESA were age dependent and increased with exposure. There was evidence that Pf155/RESA antibodies might play a role in protective immunity in this population. Since Pf155/RESA is a potential vaccine candidate antigen, the information obtained from these field studies will provide some seroepidemiologic baseline data for subsequent vaccine trials. PMID- 1449197 TI - Simulation of arbovirus overwintering: survival of Toscana virus (Bunyaviridae:Phlebovirus) in its natural sand fly vector Phlebotomus perniciosus. AB - A series of experiments were done to study the effect of simulated summer and winter temperatures on the development of Phlebotomus perniciosus (Diptera:Psychodidae) and on the survival of Toscana virus in transovarially infected insects. Sand flies maintained at 28 degrees C developed relatively fast, with adults emerging from 40 to 55 days after initial oviposition. Similar results were obtained with insects reared at 25 degrees C. In contrast, sand flies maintained at 15 degrees C developed slowly up to the fourth larval instar; at that point, further development ceased and the insects entered diapause. Diapause could be terminated by increasing the ambient temperature to 25 degrees C. The ambient temperatures at which the immature forms were reared (15 degrees C, 25 degrees C, and 28 degrees C) had no effect on the subsequent F1 adult filial infection rates with Toscana virus (49.1%, 47.5%, and 46.5%, respectively). The results of these experiments provide a model of how Toscana virus survives the winter in endemic areas by maintenance in diapausing P. perniciosus larvae. In another experiment, venereal transmission of Toscana virus was shown from transovarially infected males to non-infected virgin females. This is the first demonstration of sexual transmission of a phlebovirus by sand flies. If venereal transmission occurs in nature, it would provide an alternative method of virus amplification in the vector population, in the absence of viremic vertebrates. PMID- 1449198 TI - Cryptosporidiosis among patients with acquired immunodeficiency syndrome in Zulia State, Venezuela. AB - We studied the prevalence of Cryptosporidium in 29 patients with acquired immunodeficiency syndrome (AIDS) from Zulia State, Venezuela. They ranged in age from five months to 46 years. Two were children and 27 were adults, of which six were women. Of the 21 men, 66.6% reported homosexual behavior. Three stool samples from each patient were examined, and modified Ziehl-Neelsen carbolfuchsin staining of formalinether stool concentrates was used to identify Cryptosporidium oocysts. To detect the presence of other intestinal parasites, direct wet mounts and iron-hematoxylin-stained smears were examined. Cryptosporidium was found in 12 (41.3%) of the patients and was identified as a single parasitic infection in seven of the 12 patients (58.3%). Other pathogenic parasites encountered were Giardia lamblia (3 of 12, 25%), Entamoeba histolytica (1 of 12, 8.3%), Ascaris lumbricoides, Trichuris trichiura, and Strongyloides stercoralis (each 1 of 12, 8.3%). Blastocystis hominis, an organism with an uncertain taxonomic position and pathogenicity, was observed in three of 12 patients (25%). An inflammatory exudate was observed in 10 of 12 patients infected with Cryptosporidium. Most of the patients with this infection presented with chronic watery diarrhea and weight loss. Our results suggest that Cryptosporidium is very common in AIDS patients with diarrhea in Venezuela. However, the role of this parasite as an enteropathogen in these patients is uncertain. PMID- 1449199 TI - Lymphadenopathy associated with Leishmania braziliensis cutaneous infection. AB - Lymph node involvement by Leishmania during human cutaneous leishmaniasis was reported more than 90 years ago, but the importance of certain Leishmania strains in such dissemination remains largely speculative. We have examined 36 consecutively untreated cutaneous leishmaniasis patients early in their disease; 66.7% had enlarged lymph nodes. Patients with enlarged lymph nodes had higher anti-Leishmania immune responses than patients without such involvement, both at the IgG antibody level (mean +/- SD optical density at 492 nm = 0.163 +/- 0.089 versus 0.098 +/- 0.086; P = 0.009) and in skin test responses (12.4 +/- 10.2 mm versus 5.7 +/- 7.3; P = 0.03). Thirteen (62%) of 21 lymph node cultures and 16 (53%) of 30 cultures from cutaneous sites were positive for Leishmania. Eleven of 13 isolates from lymph nodes were characterized by a panel of monoclonal antibodies, and all were typed as L. braziliensis. Our findings stress the importance of L. braziliensis as an agent involved in the early invasion of the lymphatic system. PMID- 1449200 TI - Use of enzyme immunoassays to compare the effect and assess the dosage regimens of three Brazilian Bothrops antivenoms. The Butantan Institute Antivenom Study Group (BIASG). AB - The effect of the three main Brazilian polyspecific antivenoms on venom clearance was assessed in 118 moderately envenomed victims of bites by Bothrops species (mainly B. jararaca) in Sao Paulo State, Brazil. Serum samples taken from patients at intervals during their stay in the hospital and at followup approximately four weeks later were tested by enzyme immunoassay for the presence of whole venom and therapeutic antivenom. Results indicated that in patients treated with the standard regimen of either four (40 ml) or eight (80 ml) ampules of each antivenom, venom was cleared from the circulation within four days of antivenom administration. However, high concentrations of antivenom persisted for approximately 10 days and remained detectable until 30-50 days after administration. This suggests that patients may be being treated with excessive amounts of antivenom in Brazil. This practice increases the national cost of antivenom therapy and may contribute to the high frequency of antivenom reactions. Clinically, there was no obvious difference in the efficacy between the three antivenoms. PMID- 1449201 TI - Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency. AB - The evolution of Lyme borreliosis was examined in genetically resistant C.B-17 and susceptible C3H/He(C3H) mice homozygous for the severe combined immune deficiency (scid) gene, or their immunocompetent counterparts. The C.B-17, C.B-17 scid, C3H, and C3H-scid mice were inoculated intradermally with 10(4) Borrelia burgdorferi and examined on days 14, 21, 30, 45, and 60 after inoculation. Spirochetemia was detected through 30 days, but was cleared in all groups by 45 days. Kidney and brain were inconsistently culture positive, but spleen and ear punch samples were positive in most mice. Immunocompetent C.B-17 and C3H mice seroconverted with equivalent IgG titers to B. burgdorferi, while C.B-17-scid and C3H-scid mice did not seroconvert. Arthritis occurred in nearly all joints examined in all genotypes on day 14, was of equal severity among C.B-17, C.B-17 scid, and C3H mice, but was more severe in C3H-scid mice. By days 30 and 45, arthritis began to resolve in immunocompetent mice, with C3H mice having more severe disease than C.B-17 mice. Arthritis persisted in C.B-17-scid and C3H-scid mice. Carditis occurred to an equal degree in all groups on day 14, remained active in scid mice, but regressed in immunocompetent mice at later intervals. Many spirochetes were visualized with silver stain in inflamed synovial tissues of scid mice, and were present in other tissues in smaller numbers. These studies show that specific immunity is not involved in arthritogenesis or genetically determined susceptibility to arthritis, but is involved in arthritis and carditis regression. PMID- 1449202 TI - Renal pathology in owl monkeys vaccinated with Plasmodium falciparum asexual blood-stage synthetic peptide antigens. AB - Renal specimens from Aotus monkeys were studied by light microscopy and immunohistochemistry to examine pathologic changes following vaccination with synthetic peptides corresponding to the 35-kD, 55-kD, and 83-kD asexual blood stage antigens of Plasmodium falciparum. The monkeys were vaccinated and later challenged with P. falciparum. In the monkeys vaccinated with Centers for Disease Control peptides (group I), specimens from four of six postvaccinated animals had mild to severe mesangial proliferation and two had diffuse interstitial nephritis. Specimens from three monkeys vaccinated with Colombia peptides (group II) had mild to severe mesangial proliferation and one had interstitial nephritis. In the hybrid polymer-vaccinated monkeys (group III), specimens from three animals had mild to moderate mesangial proliferation and one had severe interstitial nephritis. On the other hand, the control group immunized with bovine serum albumin (group IV) showed that specimens from three animals had mild to severe mesangial proliferation and two had severe interstitial nephritis. In the nonimmunized group (group V), specimens from three animals had moderate to severe mesangial proliferation and two had severe and mild interstitial nephritis. Immunohistochemical analysis using the peroxidase-antiperoxidase method revealed mesangial deposits of P. falciparum antigens in 11 of 14 vaccinated monkeys and in five of 10 unvaccinated controls. These results show that treatment of monkeys with prospective malaria vaccines does not increase the frequency of occurrence or of the severity of renal lesions. These data thus provide a baseline for assessing the safety of synthetic malarial vaccines in the future. PMID- 1449203 TI - Agglutination of Plasmodium falciparum-infected erythrocytes from east and west African isolates by human sera from distant geographic regions. AB - Plasmodium falciparum-infected erythrocytes (PfE) were collected from acutely infected children in The Gambia and Tanzania and cultured for more than 30 hr until the parasites were mature trophozoites. Sera collected from these countries, other African countries, Asia, and South America were used in the PfE microagglutination test to determine whether PfE from East and West Africa share surface antigens. From the patterns of agglutination reactivity, we identified extensive antigenic diversity in surface antigens, but obtained no evidence for greater differences between isolates from East or West Africa and those within one region. The majority of sera from immune adults from The Gambia, Tanzania, Sudan, Nigeria, or Ghana were pan-agglutinating, and agglutinated all PfE isolates from The Gambia and Tanzania. Some sera from immune adults of Irian Jaya also agglutinated each of the seven African isolates, while others agglutinated many but not all of the isolates, similar to sera from immune adults of Flores, Indonesia. In contrast, sera from nonimmune adults from Colombia agglutinated few of the African isolates. It was remarkable, however, that sera from nonimmune Colombians agglutinated any African isolates. Our results are consistent with the following conclusions: some PfE surface antigen(s) are very diverse; this diversity is a feature of the parasite worldwide; the repertoire of isolate specific surface antigens, although large, includes antigens that are either identical or antigenically cross-reactive in geographically very distant parasite populations; and African adults have pan-agglutinating antibodies that may contribute to protective immunity. Such pan-agglutinating antibodies could reflect the accumulation of a large repertoire of isolate-specific antibodies. The contribution of antibody against any shared PfE surface antigen to the pan agglutinating reactivities is unknown and awaits development of the appropriate reagents. PMID- 1449204 TI - The squirrel monkey as an experimental model for Plasmodium falciparum erythrocyte rosette formation. AB - Experimental cerebral malaria was recently found to occur in the squirrel monkey Saimiri sciureus when infected with the human malaria parasite Plasmodium falciparum. This report is concerned with the existence of spontaneous rosette formation ex vivo (infected blood samples) and in vitro (cultured parasites) between red blood cells (RBC) infected with squirrel monkey-adapted P. falciparum isolates and normal squirrel monkey RBC. Transfer of P. falciparum with high rosette formation tendencies (90-100 R+) from one donor monkey to several recipients gave rise to parasites that varied extensively in their ex vivo rosette formation capacity (4-96% R+). However, all individual parasites readily form rosettes after 24 hr of in vitro culture (60-95% R+). Host factors may be involved in the modulation of rosette formation, although it is found to occur both in splenectomized and spleen-intact animals. Cross-rosette formation is seen between parasitized human RBC and normal squirrel monkey RBC and vice versa, and rosettes formed by RBC of the two hosts are similarly affected by pH, temperature, EDTA, trypsin, as well as squirrel monkey and African human hyperimmune IgG. These characteristics of rosette formation are preserved after long-term in vitro culture in human RBC. Rosettes formed by some isolates are highly sensitive to heparin while others are not, suggesting at least two distinct mechanisms of rosette formation. This idea is also supported by the observation that specific squirrel monkey antisera to heparin-sensitive strains does not dissociate rosettes formed by a heparin-resistant strain. The results suggest that rosettes and anti-rosette formation antibodies formed by squirrel monkeys and humans exhibited similar characteristics, and that the squirrel monkey is therefore a good experimental model to study erythrocyte rosette formation and cerebral malaria. PMID- 1449205 TI - Placental pathology in Plasmodium berghei-infected rats. AB - The pathologic changes in placentae of pregnant rats infected with Plasmodium berghei at different stages of gestation were studied using light and electron microscopy and immunohistochemistry. The major changes observed were thickening and duplication of the trophoblastic basement membrane, and accumulation of parasitized erythrocytes and occasional mononuclear cells in the maternal blood space. Immunohistochemical examination of nine placentae revealed that six stained positively for IgG, two for IgM, and four for P. berghei antigen. No C3 deposition was detected. The findings in this study indicate that the variable parasitologic-clinical course from benign to fatal of P. berghei infection in pregnant rats makes it a potentially valuable model of human gestational malaria infection. PMID- 1449206 TI - Human African trypanosomiasis: presence of antibodies to galactocerebrosides. AB - Improvements were made in the immunodetection of anti-galactocerebroside (anti GalC) antibody in sera of patients with human African trypanosomiasis by thin layer chromatography, enzyme-linked immunosorbent assay, and immunoadsorption. Rabbit anti-GalC antibodies were used to standardize these techniques and demonstrate their specificity. Anti-GalC antibodies were found in the sera of 42.8% of 63 patients with human African trypanosomiasis. Thirty-four control subjects living in the same endemic area were also tested. Anti-GalC levels were higher in human African trypanosomiasis patients with neurologic disturbances compared with patients without such disturbances. These antibodies were distributed mainly between the IgG and IgM classes, but 28% of the patients with human African trypanosomiasis had increased IgA levels without anti-GalC antibody activity. PMID- 1449207 TI - A polyclonal but not a monoclonal antibody to an M(r) 52-kD protein responsible for a punctate fluorescence pattern in Plasmodium falciparum merozoites inhibits invasion in vitro. AB - A monoclonal antibody, MAb H24, recognized a Plasmodium falciparum antigen with a relative molecular mass (M(r)) of 52 kD that appeared to be a rhoptry component by immunofluorescence microscopy. The antigen is synthesized during both ring and schizont stages, but pulse-chase experiments showed that it is not carried through to the next ring stage after reinvasion. It was not labeled by 3H glucosamine. The purified MAb failed to inhibit parasite invasion in vitro. The antigen was isolated using affinity chromatography, and used to produce a monospecific polyclonal antibody (PAb H24) in mice. Polyclonal antibody H24 recognized the same antigen as MAb H24 as judged by both immunofluorescence microscopy and immunoprecipitation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and was markedly inhibitory in vitro. PMID- 1449208 TI - Suppression of Plasmodium falciparum infections during concomitant measles or influenza but not during pertussis. AB - In tropical countries, concomitant infections are a continuous problem. In the Rufiji Delta, an area of Tanzania that is holoendemic for malaria, there were outbreaks of influenza A, measles, and pertussis in 1986 and 1987. Significantly lower parasitic prevalences and mean densities of malaria parasites were found in children up to nine years of age who had measles or influenza than in asymptomatic control children. In contrast, children with pertussis had a higher prevalence and mean density than controls. The clinical courses of measles, influenza, or pertussis infections did not appear to be significantly affected by concomitant malaria infections. The reasons for the suppression of Plasmodium falciparum parasitemia during these viral infections are unclear. This effect could not be explained by the presence of fever. PMID- 1449210 TI - Pathologic changes in the midgut of Culex tarsalis following infection with Western equine encephalomyelitis virus. AB - Midguts of two strains of the mosquito vector Culex tarsalis were examined by light and electron microscopy following infection with western equine encephalomyelitis virus. Infection of the highly susceptible Knight's Landing strain with high-titered blood meals resulted in pathologic changes in the midgut epithelium after 2-4 days of incubation; lesions included sloughing of epithelial cells into the lumen and necrosis of cells in situ. Infection of Knight's Landing strain mosquitoes with low-titered blood meals and infection of the less susceptible Fort Collins strain with high-titered blood meals did not result in a significant increase in detached luminal cells, with respect to uninfected controls. Sloughing of infected cells into the midgut lumen may contribute to modulation of the mosquito infection. Lesions in the midgut of Cx. tarsalis are inconsistent with traditional views that regarded arbovirus infections of mosquito vectors as non-pathologic. These findings demonstrate that mosquito pathology is not an oddity limited to the previously described interaction between Culiseta melanura and eastern equine encephalomyelitis virus, and suggest that alphaviruses in general may adversely affect their mosquito vectors in nature. PMID- 1449209 TI - Failure of a synthetic vaccine to protect Aotus lemurinus against asexual blood stages of Plasmodium falciparum. AB - The hybrid synthetic protein SPf(66), which contains small fragments of the 83 kD, 55-kD, 35-kD, and circumsporozoite antigens of Plasmodium falciparum, was studied to determine its protective capacity against malaria infection in Aotus lemurinus monkeys. Two groups of six monkeys each were immunized six times with this polymer, which was mixed with either Freund's adjuvant or aluminum hydroxide. Two groups of five animals each were used as controls and immunized with saline solution mixed with the same adjuvants. Neither antipeptide nor antimalarial antibodies developed after the six immunization doses. Regardless of this fact, the monkeys were challenged intravenously with 10(5) P. falciparum blood stage parasites, and the resultant parasitemia was followed daily on blood smears. Only one monkey from each of the groups immunized using Freund's adjuvant (both experimental and control) was protected. In those immunized using aluminum hydroxide, one animal was protected in the experimental group, but none were protected in the control group. Anti-parasite antibodies developed during the infection, but did not correlate with protection and failed to recognize SPf(66) peptide in an enzyme-linked immunosorbent assay. Immunization with the polymer did not boost natural antibodies present in two of the monkeys before the experiment. Low levels of gamma-interferon were produced in some animals, but were not correlated with protection. PMID- 1449211 TI - Variation in Aedes aegypti mRNA populations related to strain, sex, and development. AB - Translation products were used to monitor changes in gene expression between different strains and developmental stages of Aedes aegypti. Total RNA was isolated from fourth stadium larvae, male and female pupae, and male and female adults collected at fixed time intervals following pupation and ecdysis. Differences in RNA populations were assessed by in vitro translation followed by one- and two-dimensional polyacrylamide gel electrophoresis and fluorography. Variations in gene expression between sexes and during development were examined in Liverpool (LVP) and Rockefeller (RKF) Ae. aegypti strains. Sex-related differences consisted primarily of differing lengths of expression for certain polypeptides, although two-dimensional electrophoresis revealed changes in intensity of a 44-kD polypeptide with a pI of 7.9 between males and females. Fourth stadium larvae, pupae, and adults expressed different translation products, which probably correlated with developmental differences. Strain related differences were observed between LVP and RKF. PMID- 1449212 TI - Rates of peptide proteolysis measured using liquid chromatography and continuous flow fast atom bombardment mass spectrometry. AB - An immobilized digestive enzyme assay, which has been used to determine whether orally administered peptide drugs are hydrolyzed by the digestive system, was applied to the measurement of rates of proteolysis of biologically active peptides. In this study, the rates of hydrolysis by trypsin and chymotrypsin of the pressor agent angiotensin II, the peptide hormone [Arg8]vasopressin, and the peptide drug [deamino-Cys1,D-Arg8]vasopressin were measured. Enzyme immobilization prevented autolytic proteolysis and provided a stable enzyme preparation during the assays. For rate determinations, the disappearance of substrate was measured over time by using either flow injection continuous-flow fast atom bombardment (FAB) mass spectrometry with selected ion monitoring or reversed-phase high-performance liquid chromatography (HPLC) with UV absorbance detection. Compared to the HPLC method, continuous-flow FAB was faster, provided more confident identification of the analyte because molecular weight data was obtained, and could be used for all enzymatic reactions instead of only those in which complete chromatographic resolution of substrate from proteolytic fragments was obtained. The in vitro proteolytic rates measured for the vasopressins were compared to data from rat bioassays and confirmed that the limiting factor in the oral bioavailability of [Arg8]vasopressin was rapid hydrolysis by trypsin in the intestinal lumen. The more bioactive compound, [deamino-Cys1,D-Arg8]vasopressin, was more stable to chymotryptic digestion and completely resistant to trypsinization. PMID- 1449213 TI - Comparative study of photodissociation and surface-induced dissociation by laser desorption Fourier transform mass spectrometry. AB - Photodissociation (PD) and surface-induced dissociation (SID) are compared for structural analysis of several nonvolatile compounds analyzed by laser desorption Fourier transform mass spectrometry (LD/FTMS). SID and PD of a porphyrin and two metalloporphyrins were investigated using a variety of experimental conditions. Optimum structural information is obtained from PD when parent ions are irradiated for relatively long times (10-30 s) using 575-nm radiation and short times (0.5-1 s) using 308- or 388-nm radiation. Shorter irradiation times in the visible region resulted in less efficient production of structurally significant product ions, while longer times in the ultraviolet region produced more nonspecific fragment ions, apparently at the expense of more structurally significant fragment ions. SID conversion efficiencies for the porphyrins are estimated for collision energies from 25 to 360 eV, with maximum conversion efficiency found using 62- and 115-eV collision energies for the two porphyrins studied. Results from a concurrent study on the combined use of PD and SID for MS/MS/MS are discussed in the context of these results. The MS3 ion spectra generated by the two dissociation techniques differ more significantly than MS2 product ion spectra. These data suggest some general guidelines for MSn studies of nonvolatile compounds analyzed by LD/FTMS, employing PD and SID for ion activation. PMID- 1449214 TI - Application of plasma desorption mass spectrometry to molecular weight determination of human interleukin-4 secreted by a Chinese hamster ovary line. PMID- 1449215 TI - Specificity of interneuronal connections. AB - A fundamental problem of neurobiological research is how specific connections between individual neurons are established and maintained. In this report different levels of neuronal specificity are described. Some neuronal populations display region specificity, but within the target region they establish synapses with a variety of neurons. A characteristic feature of the afferent innervation of hippocampal neurons is that many fibers terminate in a laminated fashion. Such a layer specificity is known for the afferents from the entorhinal cortex and for the mossy fibers. The entorhinal afferents terminate in the outer molecular layer of the fascia dentata and in the stratum lacunosum-moleculare of the hippocampus proper. The mossy fibers display both region specificity and layer specificity: they form numerous synapses in hippocampal region CA3 but never invade CA1; in CA3 they are restricted to stratum lucidum. An extremely high degree of neuronal specificity is observed in the case of the axo-axonic or chandelier cells. The axons of these neurons specifically terminate on the axon initial segments of projection neurons in the neocortex, hippocampus and fascia dentata. Thus, these cells not only display a target cell specificity but a selectivity for a distinct portion of the target cell's membrane. Some of the factors that contribute to these different levels of neuronal specificity are briefly discussed. Positional cues as well as diffusible molecules from the target region may guide the outgrowing growth cone to its target. Molecular interactions between pre- and postsynaptic membranes, the functional load of the synaptic contact, and the selective death of a number of neurons and synapses further determine the specificity of interneuronal connections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449216 TI - Synaptic reorganization in developing and adult nervous systems. AB - Evidence is accumulating that synapse reorganization already starts during development, soon after first synapses appear. Although remodeling continues throughout ontogenesis, there are apparently (critical) periods which are characterized by enhanced synaptic reorganization. In certain parts of the peripheral and central nervous system, synapses may undergo remodeling which leads to changes in their transmission efficiency or complete elimination of the synaptic junctions, even in adulthood. Synaptic reorganization includes progressive and regressive changes on branches of dendritic and/or axonal processes that accompany the formation and elimination of synapses. Three modes of elimination are presently known: Physiological cell death of synaptically connected neurons is involved, especially during certain developmental periods, during hormonally induced metamorphosis and in the olfactory bulb. Synaptic disconnection ("stripping") and lysosomal degradation predominantly of presynaptic elements occur under different conditions. In order to undergo plastic changes, neurons seem to respond to exogenous or intrinsic factors such as lesions (partial deafferentation and axotomy), long-lasting changes in neuronal activity (e.g. drug application and sensory deprivation), hormonal influences (e.g. sexual hormones) or learning conditions. PMID- 1449217 TI - Molecular control of neural plasticity by the multifunctional growth factor families of the FGFs and TGF-beta s. PMID- 1449218 TI - Neuronal specificity and plasticity in the autonomic nervous system. AB - The autonomic nervous system is divided into the sympathetic, parasympathetic and enteric subdivisions. The present review is focussed upon the highly specialized reflex organization and neurochemistry of sympathetic parasympathetic neurons. The currently available informations allow to conclude that autonomic control of each peripheral target tissue is specifically regulated under normal conditions but nevertheless able to respond to altered conditions by changes in neural activity and mediator expression. PMID- 1449220 TI - Myocardial bridges over coronary arteries in Cercopithecus. AB - The presence of myocardial bridges over the coronary arteries has been studied in 29 monkey (Cercopithecus aethiops) hearts. The great resemblance between the Cercopithecus subepicardial arterial net with the corresponding one in humans has been revealed. There is a high incidence (83%) of myocardial bridges only over the ventricular branches of both coronary arteries. Myocardial bridges are usually (90%) located over the left coronary artery branches, and the left anterior interventricular branch is the most frequently (69%) overbridged vessel. The bridges are always single over the vessel examined and their length varies from 0.5 mm to 31.6 mm. No statistically significant sexual difference in myocardial bridges distribution is reported. PMID- 1449219 TI - The hypoglossal-facial anastomosis as model of neuronal plasticity in the rat. AB - Hypoglossal-facial cross anastomosis (HFA) causes regeneration with change of function, as the axotomized hypoglossal motoneurons sprout into the facial plexus and reinnervate the mimic musculature. Following HFA, hypoglossal-hypoglossal single anastomosis (HHA) and resection of 8-10 mm peripheral hypoglossal nerve in 190 female adult Wistar rats, we compared the axon reactions in the hypoglossal nucleus during 1) regeneration with change of function, 2) regeneration with restoration of original function and 3) degeneration of the nucleus. Following postoperative survival times of 1-16 weeks we estimated the volume of the hypoglossal nucleus and counted the number of hypoglossal neurons with the physical disector on both sides of the brainstem. Additional sections of the same animals were reacted with anti-synaptophysin, anti-GFAP and the isolectin Griffonia simplicifolia I-B4 (GSA I-B4) as cytochemical markers for presynaptic boutons, activated astroglia and microglia. After HHA and HFA all hypoglossal neurons survive and the volume of the hypoglossal nucleus remains constant. Resection of the hypoglossal nerve leads to the loss of one third of the hypoglossal neurons and of one third of the volume of the hypoglossal nucleus within 16 weeks post operation. Hypoglossal-facial anastomosis and hypoglossal hypoglossal anastomosis differ in postoperative swelling of the hypoglossal nucleus, microglia and astroglia activation and the duration of synaptic stripping. All differences are limited to the acute growth phase during regeneration. It is concluded that hypoglossal-facial anastomosis provides more stimulation and facilitates faster recovery of the hypoglossal nucleus than does hypoglossal-hypoglossal anastomosis. PMID- 1449221 TI - Proteinase, phosphatase and glucuronidase activities in the growing mandible and temporomandibular joint of the guinea pig. AB - This study investigated the effect of muscle function and occlusal form on the activity levels of several enzymes present in the mandible or temporomandibular joint of the guinea pig. Restriction of maxillary width and asymmetric function of the mandible was caused in 12 animals at the age of 10 days, as described in the accompanying paper (Isotupa et al. 1992). Tissue samples from six anatomical sites were obtained from the animals sacrificed 4, 8, or 12 weeks after manipulation (4 animals in each group). Six age-matched animals acted as controls. Five samples were from the following sites of the mandible: the condylar cartilage, the lower and upper parts of processus angularis, and the anterior and posterior halves of the condyle neck. A sample was also obtained from fossa mandibularis of the temporal bone. Buffer extracts of powderized samples were studied for acid and alkaline phosphatase, glucuronidase and two types of proteolytic activity. Although the asymmetric manipulation of occlusion caused observable, localized asymmetric growth, the enzyme findings were not consistently asymmetric. Manipulation generally increased all enzyme activities regardless of whether apposition or resorption was involved. The activities of alkaline phosphatase more consistently showed this pattern, and changes in enzyme activities seemed to be sensitive, reflecting cellular or molecular level of growth. The enzyme activities may also reflect a certain type of after-effect of irritation, or a healing period. The inclusion of several types of enzyme determinations is recommended to complete macroscopic measurements. Subsequent chromatographic and electrophoretic studies are also useful. PMID- 1449222 TI - Influence of asymmetric occlusal relationships and decreased maxillary width on the growth of the facial skeleton in the guinea pig. AB - The purpose of this study was to evaluate the effect of muscle function and occlusal form on mandibular growth in guinea pigs. We hypothesized that restriction of maxillary width and asymmetric function of the mandible would lead to mandibular asymmetry. The hard palate of 12 animals was exposed at the age of ten days, and cyanocrylate was used to close the midpalatal suture in order to restrict transverse maxillary growth. The right incisors and right molars were ground obliquely at the time of surgery and every two weeks thereafter until the animals were sacrificed 4, 8 and 12 weeks later (four animals in each time group). Six age-matched animals served as controls. Dorsoversal x-rays were taken at sacrifice, followed by the removal of small biopsies from six different sites of the maxillomandibular skeleton for biochemical studies, which will be reported separately. Relative to controls, the treated animals exhibited a narrow maxilla and asymmetry in the height of the ramus and in the length of the mandible from the mental foramen to the angular process. The maximum width between the angular processes of the mandible was extremely narrow, as was the condylar neck especially on the right side. It was concluded that abnormal masticatory muscle function caused by occlusal deviation led to a narrowing and a slight asymmetry of the mandible in the growing guinea pig. PMID- 1449223 TI - Age-related changes in cholinergic and noradrenergic transmission in the rat cerebellum. A histochemical and immunocytochemical study. AB - The histochemical and immunocytochemical distribution of some cholinergic and noradrenergic markers was compared in the cerebellum of young adult (3-month old) and aged (24-month old) Wistar rats. A decrease in the density and staining of acetyl cholinesterase (AChE) positive fibers, puncta and Golgi cells was found in both the cerebellar cortex and nuclei of aged rats. The age-related changes in choline acetyltransferase immunoreactivity were less pronounced than the changes in AChE activity. A reduction in the density of catecholamine fluorescent fibers and puncta was observed in the cerebellar cortex during aging. In aged rats the increase in monoamine oxidase (MAO)-A activity was more pronounced than the increase in MAO-B activity. PMID- 1449224 TI - Differentiation of the brain stem structures in the salamander, Hynobius nebulosus. AB - Differentiation of the internal structure of the brain stem was analyzed in the salamander with special reference to neurons distributed in the marginal layer. It was found that the salamander brain stem was at first composed exclusively of the mantle layer. The marginal layer later differentiated peripherally. In these developmental stages, the mantle and marginal layers were clearly differentiated: the former was made up exclusively of the somata, while the latter was composed mainly of nerve fibers. As the development proceeded, these organization patterns were modified: a few cells migrated into the marginal layer. Cells migrating into the marginal layer formed various nuclei and layers such as the raphe nuclei, reticular formation and superficial cellular layers of the optic tectum. In later development stages, fibers in the marginal layer were myelinated, and neurons in the marginal layer were observed to become embedded among numerous myelinated fibers. Cytologically, the majority of neurons in early developmental stages were unipolar, extending a process peripherally into the marginal layer. In later developmental stages, neurons in a deep zone of the mantle layer remained unipolar, whereas those in the marginal layer and in the superficial zone of the mantle layer differentiated into multipolar cells. Thus, (1) the marginal layer differentiated peripherally as a cell free region; (2) cells in the mantle layer later migrated into the marginal layer, changing into multipolar neurons; (3) cells in the marginal layer formed reticular formation as well as various nuclei and layers in the peripheral white matter; and (4) as development proceeded, fibers in the marginal layer became myelinated. PMID- 1449225 TI - Vascular ontogeny of the septal region in rats. AB - The development of the arterial and venous systems of the septum was studied in rat brains injected daily with India ink, from the 11th embryonic (E) until the first postnatal day. Arterial blood is supplied to the septum by the unpaired hemispheric artery, the stem and septal branches of which are to be recognized on the 14th and 15th embryonic days respectively. At earlier stages, e.g. on E12, a capillary network, the hemispheric plexus, can be seen between the two hemispheres contributing to the blood supply of the septum during the early phase (E14 to E18) of development. From E18 onwards, the arterial supply of the septum is derived only from direct branches of the hemispheric artery; one group of them being dorsal (infracallosal) and the other ventral (subcallosal). The venous drainage of the septum is bidirectional: 1) Veins of the ventral group leading to the interperioptic sinus are seen on E14. At first they collect blood only from a small rostral portion of the septum, but later their territory expands to include the anteroventral two-thirds of the septum. 2) The dorsal septal veins drain into the great cerebral vein (of Galen), or into the superior sagittal sinus directly. Initially, twigs run directly into the great cerebral vein. These later become the tributaries of the internal cerebral vein, which appears on E17 or E18. Until E18 this dorsally-directed drainage predominates, whereas at birth it becomes restricted to one third of the septum as a result of a gradual regression. The development of both arterial and venous circulations of the septum is complete at birth. PMID- 1449226 TI - A study of human foot length growth in the early fetal period. AB - The length of the human fetal foot was studied in 106 feet from 53 unfixed staged human fetuses (35 males and 18 females) by means of the allometric formula log Y = log b+k log X. The gestational age ranged from 13 to 26 weeks postconception. The measurement taken from the heel to the tip of the longest toe was regarded here as the maximum length of the foot. Growth in length of the foot was analysed in relation to crown-rump length. Our results show that foot length growth is correlated to crown-rump growth and is allometrically positive. No statistically significant difference was found between right and left feet or between male and female fetuses. PMID- 1449227 TI - Numerical simulation of aerosol particle transport by oscillating flow in respiratory airways. AB - Particle transport by oscillating flow in a tapered channel or in a tapered tube was computed from the complete equations of motion. These geometries represent a simplified model of the divergent flow field of the mammalian bronchial tree. The computed deformation profile of a line of particles, transported by the oscillatory motion, was compared with prior experimental results and analytical calculations. All three methods agree that there is transport in the divergent direction of the tube by an axial stream of steady drift in the core for moderately high frequency of oscillation (Womersley parameter in the range of 1 to 10). Bidirectional flow is established by an annular stream in the convergent direction, with no net flow on integral cycles of the oscillating fluid. At higher frequency, however, the steady stream transforms to a different shape in the tapered tube, with transport in the divergent direction nearer the walls of the tube, rather than in the core. Transport by the continuing streams with oscillatory ventilation of the respiratory tract should deliver medicinal aerosols of low intrinsic particle mobility to the peripheral regions of the lungs. PMID- 1449228 TI - Orthopedic prosthesis fixation. AB - The fixation of orthopedic implants has been one of the most difficult and challenging problems. The fixation can be achieved via: (a) direct mechanical fixation using screws, pins, wires, etc.; (b) passive or interference mechanical fixation where the implants are allowed to move or merely positioned onto the tissue surfaces; (c) bone cement fixation which is actually a grouting material; (d) biological fixation by allowing tissues to grow into the interstices of pores or textured surfaces of implants; (e) direct chemical bonding between implant and tissues; or (f) any combination of the above techniques. This article is concerned with various fixation techniques including the potential use of electrical, pulsed electromagnetic field, chemical stimulation using calcium phosphates for the enhancement of tissue ingrowth, direct bonding with bone by glass-ceramics and resorbable particle impregnated bone cement to take advantages of both the immediate fixation offered by the bone cement and long term fixation due to tissue ingrowth. PMID- 1449229 TI - Modeling the circulation with three-terminal electrical networks containing special nonlinear capacitors. AB - Development, first of analog and later of digital computers, as well as algorithms for analysis of electrical circuits, stimulated the use of electrical circuits for modeling the circulation. The networks used as building blocks for electrical models can provide accurate representation of the hydrodynamic equations relating the inflow and outflow of individual segments of the circulation. These networks, however, can contain connections in which voltages and currents have no analogues in the circulation. Problems arise because (a) electrical current must flow in closed loops, whereas no such constraints exist for hydraulic models; and (b) electrical capacitors have a number of characteristics that are not analogous to those of hydraulic compliant chambers. Disregarding these differences can lead to erroneous results and misinterpretation of phenomena. To ensure against these errors, we introduce an imaginary electrical element, the nonlinear residual-charge capacitor (NRCC), with characteristics equivalent to those of a compliant chamber. If one uses appropriate circuit connections and incorporates the residual-charge capacitor, then all voltages and currents in the model are proper analogues of pressures and flows in the circulation. It is shown that the capacitive current represents the rate of change of volume of blood inside the vessel, as well as the rate of the corresponding displacement of volume of the surrounding tissue. PMID- 1449230 TI - The impedance of a spherical monopolar electrode. AB - The impedance of a monopolar electrode immersed in an environmental volume conductor consists of two parts; the impedance of the active electrode electrolyte interface, and the resistance of the environmental conductor. Two studies were carried out to quantitate these components. First, impedance frequency data were collected for five spherical stainless-steel electrodes (ranging from 0.473 to 1.11 cm in diameter) immersed in 0.9% saline (p = 70 omega cm). Impedance measurements were made from 100 Hz to 100 kHz and two sets of data were obtained; one before and one after each electrode was polished with fine emery paper. At low frequency, the measured impedances were high and varied with electrode surface preparation. However, above a transition frequency, the impedances were resistive, independent of the electrode surface preparation, and equal to rho/2 pi d as predicted from the theory. This study indicates that the low frequency impedance of a monopolar electrode is dominated by the impedance of the electrode-electrolyte interface. Above a transition frequency, the resistance of the environmental conductor dominates, the value of this resistance depending on the electrode geometry and the resistivity (rho) of the environmental conductor. A second study was conducted, to examine the effect of the distance to the indifferent electrode. A frequency (100 kHz) above the transition frequency was used and impedance data were collected for various distances between the monopolar and indifferent electrodes. The measured resistance increased asymptotically as the distance between the electrodes was increased. When the indifferent electrode diameter was at least 10 times the diameter of the spherical monopolar electrode, the measured resistance was within 5% of the value predicted for an indifferent electrode at infinity. PMID- 1449232 TI - Optimization of single electrode tactile codes. AB - The effects of a frequency modulated electrocutaneous signal's (code's) characteristics on the interpretability of the signal were investigated using an electrocutaneous tracking approach. The characteristics investigated include the functional relationship (exponential and hybrid) between an informational signal and the stimulation frequency, the range of stimulation (2-50 Hz and 2-100 Hz), and the impact of pulse width compensation on a code's efficacy. The interpretability of six different single bipolar electrode codes was examined by 30 subjects using a balanced incomplete block experimental design. Codes with exponentially shaped transfer functions resulted in generally lower electrocutaneous tracking errors than codes utilizing hybrid-shaped transfer functions. Hybrid codes had a transfer function that was linear in the lower frequency range and exponential in the higher frequency range. Codes with a 2-100 Hz frequency range were interpreted better than codes with a 2-50 Hz frequency range. The use of pulse width compensation to maintain a more even level of stimulation intensity had a slightly negative effect on the subjects' abilities to cutaneously track the information signal. PMID- 1449231 TI - Spatial variation of aortic wall oxygen diffusion coefficient from transient polarographic measurements. AB - Polarographic current transients following a voltage step (turn-on transient) were measured with bare cathodes (25 microns diameter) and shallowly recessed oxygen microelectrodes (< 5 microns diameter). Except for the initial part of the current transient, the experimental measurements were in excellent agreement with simple models in the literature, which predict an inverse relationship with square root of t. Turn-on transients were measured in aqueous solutions with known physical properties, and in aortic wall tissue from three different species (n = 6 rabbits, n = 3 dogs, and n = 1 miniature pig). Oxygen diffusion coefficients (D) were determined in vitro by comparing time constants measured by the same microelectrode in saline and in strips of aortic wall tissue at 37 degrees C. On the inner side (endothelium and intima) of the aorta, D averaged (+/- S.E.) 7.0 (+/- 0.8) x 10(-6) cm2/s in 6 rabbits, 6.4 (+/- 1.0) x 10(-6) cm2/s in 3 dogs, and was 4.6 x 10(-6) cm2/s in the pig. On the adventitial side, D was 9.5 x 10(-6) cm2/s in 1 rabbit, 11.4 (+/- 1.2) x 10(-6) cm2/s in 3 dogs, and 8.1 x 10(-6) cm2/s in the pig. For every aortic strip on which D was measured from both sides, D for the inner wall was always lower, overall by a little more than one third (p < 0.001). The lower D on the endothelial side may limit oxygen transport to the vascular wall and play a role in atherogenesis. PMID- 1449233 TI - Development of a computer model to predict strains in the individual fibers of a ligament across the ligamentous occipito-atlanto-axial (C0-C1-C2) complex. AB - A fresh ligamentous occipito-atlanto-axial (C0-C1-C2) complex was appropriately prepared and serially sectioned into thin slices along the transverse planes. The bony outlines from these slices were digitized and assembled in the proper manner to obtain a three-dimensional model of the complex using the AutoCAD system. Various ligaments were identified on the model and strains in individual fibers of a ligament were predicted based on the principles of rigid body mechanics. The ligament behaviors in axial rotation, flexion, and extension modes were analyzed. The capsular ligament fibers were predicted to undergo strains in all modes. Furthermore, these ligaments experienced the largest strain among the ligaments analyzed. Fibers within a ligament were found to respond differently; some were more active than the others and some did not experience any strain at all. A differential behavior in the right and left side alar ligament fibers was also found in axial rotation. The transverse ligament was predicted to wrap around the dens during axial rotation. The strain within a fiber was found to be a function of the initial length (ligament laxity) and its distance from the center of rotation. PMID- 1449235 TI - Annals Index 1988/1989. PMID- 1449236 TI - Report and abstracts of the First International Workshop on Chromosome 9. Held at Girton College Cambridge, UK, 22-24 March, 1992. PMID- 1449234 TI - Computationally efficient algorithms for convection-permeation-diffusion models for blood-tissue exchange. AB - Analysis of data on tissue depositions obtained by positron tomographic or NMR imaging, or of multiple tracer outflow dilution curves, requires fitting data with models composed of aggregates of capillary-tissue units. These units account for heterogeneities of flows and multisolute exchanges between longitudinally distributed regions across capillary and cell barriers within an organ. Because the analytic solutions to the partial differential equations require convolution integration, solutions are obtained relatively efficiently by a fast numerical method. Our approach centers on the use of a sliding fluid element algorithm for capillary convection, with the time step set equal to the length step divided by the fluid velocity. Radial fluxes by permeation between plasma, interstitial fluid, and cells and axial diffusion exchanges within each time step are calculated analytically. The method enforces mass conservation unless there is regional consumption. Solution for a 2-barrier, 3-region model, accurate to within 0.5%, are 100 to 1000 times faster than the corresponding, purely analytic solution, and over 10,000 times for a 4-region model. Applications include multiple indicator dilution studies of kinetics of transcapillary exchange and positron emission tomographic studies of the mechanisms of substrate transport into cells of organs in vivo. PMID- 1449237 TI - Algorithms for a location database. AB - The algorithms that drive the ldb location database are described. The program captures data on genetic and physical maps and combines information from different sources into a summary map. To assure portability it was developed in Fortran on a SUN SPARCStation under Unix. The algorithms, which combine rule based seriation with a minimum deviance bootstrap, allow investigators and chromosome committees to produce a composite location in Mb that integrates partial maps. The program and manual are now available from the authors. PMID- 1449238 TI - A study on Lu-null families in South Wales. AB - Red cells of 75614 blood donors in South Wales were screened with anti-Lu(b) revealing 54 Lu(b-) donors of which 15 were also Lu(a-) giving a frequency of 0.0002 for the Lu(a-b-) phenotype in South Wales. The families of 11 Lu-null propositi were investigated to determine which of the three known genetic backgrounds, dominant, recessive or X-linked recessive, was responsible for their Lu-null phenotype. In 10 of the 11 families the Lu-null phenotype was caused by the dominant suppressor gene In(Lu). The first reported family demonstrating independence of In(Lu) and LU, through the Au groups, is described together with the third family demonstrating suppression of P1 by In(Lu). The families showed that In(Lu) is not closely linked to HLA. The genetic background for the 11th propositus was not determined; homozygosity of the silent allele LU is a possible but unproved explanation. PMID- 1449239 TI - Interphase cytogenetics of the ICF syndrome. AB - Interphase behaviour of centromeric heterochromatin of chromosomes 1 and 16 has been investigated in lymphocytes and fibroblasts of patients with ICF syndrome and of normal subjects with non-isotopic in situ hybridization, using the satellite II-related probe pHuR 195. We found evidence for interphase somatic pairing in ICF lymphocytes with a frequency higher than that found in normal cells. Lymphocytes of ICF patients showed nuclear protrusions and micronuclei and these nuclear abnormalities consistently involved a hybridization signal. Somatic pairing was also present in fibroblasts, but with frequencies similar in normal and ICF subjects. The fibroblasts do not have the major chromosomal abnormalities found in lymphocytes. The degree of heterochromatin condensation in fibroblasts was lower than that in lymphocytes and we postulate that the more decondensed state of chromocentres in the fibroblasts could be the reason for the absence of the major chromosomal abnormalities. PMID- 1449240 TI - Long-term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa-responsive dystonia. AB - Dopa-responsive dystonia (DRD) is one form of childhood-onset idiopathic torsion dystonia. Adult-onset parkinsonism has appeared in several previously unaffected members in families with DRD suggesting that this may be an additional phenotypical expression of the disease. We report a family with DRD in which 2 women and 1 man, unaffected by dystonia, developed tremor-onset parkinsonism after age 50 years. The women continue on a low dosage of levodopa after 9 and 13 years of treatment, with a stable, nearly complete, symptomatic response. This contrasts to the typical long-term treatment complications observed in patients with Parkinson's disease. We assessed nigrostriatal dopaminergic function in the proband, with typical DRD, and the 2 women with parkinsonism using 6-[18F]fluoro L-dopa positron emission tomography. All 3 had normal striatal 6-[18F]fluoro-L dopa uptake. These observations provide compelling evidence that "benign" adult onset parkinsonism may be an expression of the disease in some members of families with DRD and does not support consideration of the DRD gene as a risk factor for development of Parkinson's disease. There may be considerable clinical heterogeneity in DRD depending on the age at onset. PMID- 1449241 TI - The identification of presymptomatic parkinsonism: clinical and [18F]dopa positron emission tomography studies in an Irish kindred. AB - An Irish kindred is described in which 5 of 10 siblings in the fourth or fifth decade of life developed an akinetic-rigid syndrome clinically indistinguishable from idiopathic Lewy body Parkinson's disease. Four of these patients were scanned by positron emission tomography (PET) with [18F]dopa after clinical diagnosis and in all, a profound impairment of tracer uptake into the striatum was recorded. The fifth patient was initially scanned at a time when he was asymptomatic and normal by clinical examination. His scan showed impaired tracer uptake, indicating a subclinical defect in the presynaptic nigrostriatal system. Within months of his scan, he too developed subtle symptoms and signs of parkinsonism although there was little further clinical progression or change in his PET scan over the following year. A clinically normal sibling was also scanned and found to have subclinical impairment of [18F]dopa uptake in the putamen. The 19-year-old daughter of an affected sibling had a mild postural tremor but no other symptoms or signs. The [18F]dopa uptake in her putamen fell at the borderline between normal and parkinsonian values. This study confirms that PET can identify preclinical parkinsonism in at-risk subjects. The finding of abnormalities in several clinically unaffected family members suggests that family studies based on clinical assessment alone may miss a significant number of subclinically affected individuals, leading to an underestimate of any genetic component to Parkinson's disease. PMID- 1449242 TI - Adenosine: a potential mediator of seizure arrest and postictal refractoriness. AB - Adenosine is a potent inhibitory neuromodulator and has been proposed as an endogenous anticonvulsant. Depth electrodes modified to include a microdialysis probe were implanted for 10 to 16 days in the hippocampi of 4 patients with intractable complex partial epilepsy to test the hypothesis that during seizures extracellular adenosine reaches levels that may depress epileptiform activity. Samples were collected bilaterally at 3-minute intervals before, during, and after a single, spontaneous-onset seizure in each patient. All seizures commenced in one hippocampus and propagated to the contralateral hippocampus. Extracellular adenosine levels increased by 6- to 31-fold with the increase significantly greater in the epileptogenic hippocampus. During seizures, levels of adenosine in the dialysate reached concentrations as high as 2.5 microM, reflecting extracellular concentrations of approximately 65 microM. Adenosine at concentrations of 40 to 50 microM depresses epileptiform activity in vitro, so the levels we report may suppress seizure activity in vivo. Moreover, adenosine levels remain elevated above basal values for the entire 18-minute postictal period. These data support the role of adenosine in mediating seizure arrest and postictal refractoriness and suggest that treatments which facilitate adenosine may be effective in preventing seizures. PMID- 1449243 TI - Effectiveness of botulinum toxin administered to abolish acquired nystagmus. AB - We injected botulinum toxin into the horizontal rectus muscles of the right eyes of 2 patients who had acquired pendular nystagmus with horizontal, vertical, and torsional components. This treatment successfully abolished the horizontal component of the nystagmus in the injected eye in both patients for approximately 2 months. Both patients showed a small but measurable improvement of vision in the injected eye that may have been limited by coexistent disease of the visual pathways. The vertical and torsional components of the nystagmus persisted in both patients. In 1 patient, the horizontal component of nystagmus in the noninjected eye increased; we ascribe this finding to plastic-adaptive changes in response to paresis caused by the botulinum toxin. Such plastic-adaptive changes and direct side effects of the injections--such as diplopia and ptosis--may limit the effectiveness of botulinum toxin in the treatment of acquired nystagmus. Neither patient elected to repeat the botulinum treatment. PMID- 1449244 TI - Serial cranial and spinal cord magnetic resonance imaging in multiple sclerosis. AB - Twenty-nine mildly disabled patients with multiple sclerosis underwent serial clinical and magnetic resonance imaging (MRI) evaluations (pre- and postgadolinium cranial and spinal cord MRI) on at least 3 occasions at 13-week intervals and during periods of suspected relapse. Using clinical judgment of the presence of recent active disease as the gold standard, combined MRI studies confirmed the clinical impression of active disease in 93% of follow-up visits (sensitivity) and the absence of active MS in 63% of follow-up visits (specificity). None of the cranial and spinal MRI-detected abnormalities disappeared. Gadolinium administration particularly increased the yield of spinal MRI. Cranial MRI alone detected 80% of the MRI-active visits. Clinical and MRI concordance was significantly better for the presence of recent disease activity than for the anatomical localization of the presumed site of activity. MRI evidence of apparent ongoing disease activity was seen more frequently in patients believed to have active multiple sclerosis in the preceding year (13 of 21) than in patients who had been in clinical remission for at least the 2 preceding years (2 of 8). Although clinical evidence of new disease activity was much less common in patients with active, chronic-progressive disease (1 of 8) than in patients with active, relapsing disease (9 of 13), the proportion of patients with either infrequent relapses, frequent relapses, or slow chronic progressive disease in the preceding year in whom MRI activity developed and the pattern of this new MRI activity was similar between these types of active patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449245 TI - HTLV-I-specific cytotoxic T lymphocytes in the cerebrospinal fluid of patients with HTLV-I-associated neurological disease. AB - Recently, it has been shown that in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated neurological disease, high levels of HTLV-I-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood. These CTLs predominantly recognized products of the pX region of HTLV-I, had a CD8+ phenotype, and were human leukocyte class I restricted. Moreover, these responses were not detected in asymptomatic, HTLV-I-seropositive individuals. This implied a role for these CTLs in the pathogenesis of the neurological disorder associated with HTLV-I. We have extended these observations by demonstrating HTLV-I-specific CTLs directly from lymphocytes obtained from the cerebrospinal fluid of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Uncultured cerebrospinal fluid lymphocytes were used directly as effectors on a variety of targets expressing HTLV-I. These cells were lysed in a virus-specific and HLA class I-restricted manner. Moreover, the cerebrospinal fluid lymphocytes were sorted into purified CD8+ populations, cloned by limiting dilution, and assayed for CTL activity. An exceedingly high proportion of these resultant lines were shown to be cytolytic and precursor frequency analysis indicated that as many as 1 in 500 cells were HTLV-I-specific CTLs. The majority of these CTL lines recognized HTLV-I gene products encoded within the pX region of HTLV-I. The significance of these HTLV-I-specific CTLs in the central nervous system of patients with HTLV-I-associated neurological disease is discussed with regard to the potential role of CTLs in the pathogenesis of this disease. PMID- 1449246 TI - Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. AB - Abnormalities in the blood-brain barrier (BBB) may be important in mediating some of the tissue damage that accompanies human immunodeficiency virus (HIV) infection of the brain, as well as in facilitating viral entry into the central nervous system. Accordingly, immunohistochemical detection of fibrinogen (FIB) and immunoglobulin G (IgG) was used as a marker of vascular permeability in formalin-fixed, paraffin-embedded brains of patients with acquired immunodeficiency syndrome (AIDS) who had HIV encephalitis (HIVE) (n = 17) and those who did not have HIVE (n = 16); nonimmunosuppressed patients served as control subjects (n = 22). The sex ratios and postmortem intervals were similar in all groups (p > 0.05), but the age of the two AIDS groups were younger than the control group (43.2 and 40.9 versus 62.5 yr; p < 0.05). The two AIDS groups had higher immunostaining for FIB and IgG than the control group (p < 0.001 and p < 0.0001, respectively) but did not differ from one another. Furthermore, the two AIDS groups had a significantly higher incidence of combined extravasation of both FIB and IgG, whereas the control group had a significantly higher incidence of negative staining for both proteins (p < 0.002). More than 95% of the microglial nodules of HIV were negative for serum proteins; however, all focal lesions with tissue necrosis, including lymphoma, opportunistic infections, and HIV (rarely), contained extravasated serum proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449247 TI - Disease-specific patterns of locus coeruleus cell loss. AB - Computer visualization techniques were used to map and to quantitatively reconstruct the entire locus coeruleus, including the nucleus subcoeruleus, to compare the topographic patterns of cell loss in postmortem brains from patients with Parkinson's disease, Alzheimer's disease, and Down syndrome. There was comparable cell loss in all three diseases (approximately 60%) compared with aged normal subjects, and there was a significant loss of nucleus subcoeruleus cells specifically in patients with Parkinson's disease (63%). There was a significant positive correlation between the magnitude of locus coeruleus cell loss and the duration of Alzheimer's disease, but no such correlation was found for Parkinson's disease. In patients with Parkinson's disease, there was comparable cell loss throughout the rostral-caudal extent of the nucleus; however, in patients with Alzheimer's disease and Down syndrome, the greatest cell loss always occurred within the rostral portion of the nucleus, with a relative sparing of caudal cells. These data are consistent with the hypothesis that cell loss in Parkinson's disease is the result of a pathological process that attacks the catecholaminergic cells of the locus coeruleus and the subcoeruleus in general; in Alzheimer's disease and Down syndrome, however, the pathological process only affects the rostral, cortical-projecting locus coeruleus cells and spares the caudal, noncortical-projecting cells. PMID- 1449248 TI - Suppression of postischemic epileptiform activity with MK-801 improves neural outcome in fetal sheep. AB - To determine the effect of suppression of epileptiform activity that develops after hypoxic-ischemic injury in the immature brain, chronically instrumented near-term fetal sheep (119-133 days) were subjected to 30 minutes of complete cerebral ischemia: 6 were given a 0.3-mg/kg bolus of MK-801 at 6 hours after the insult followed by continuous infusion of 1 mg/kg over the next 36 hours, and were compared to 6 control sheep. Electrocorticographic activity and edema within the parasagittal region of the cortex were quantified with real-time spectral analysis and impedance measurements, respectively. Histological outcome was assessed 72 hours later. The intense epileptiform activity seen from 9 +/- 2 to 30 +/- 3 hours in the control group was completely suppressed in the MK-801 treated group. The onset of secondary cortical edema was delayed from 9.4 +/- 1.1 hours to 14.8 +/- 0.7 hours (p < 0.01). Neuronal damage was reduced, particularly in the lateral cortex and hippocampus (p < 0.05). Infarction of the parasagittal cortex was not prevented. These results suggest that N-methyl-D-aspartate mediated epileptiform activity that develops after a global hypoxic-ischemic insult worsens neuronal outcome in the immature brain. PMID- 1449249 TI - Electron transfer complex I defect in idiopathic dystonia. AB - It has been suggested that dystonia is caused by an autosomal gene with reduced penetrance and a consequent biochemical abnormality affecting cell activity within the basal ganglia. No consistent biochemical disturbance has been identified. In the present study, activities of the mitochondrial electron transfer complexes were measured in platelets of 31 patients with idiopathic dystonia. Enzyme assays of these patients were compared to measurements in 28 control subjects. A significant decrease of complex I activity was observed in the majority of the patients, whereas the activities of other electron transfer complexes were normal. The severity of the complex I defect was more pronounced in patients with the segmental or generalized form than in those with focal dystonia. Complex I activity was not age dependent in the patients or control subjects. Although the electron pathway in complex I is disturbed in patients with idiopathic dystonia, complex I protein content seems to be normal. Whether abnormalities of complex I activity play a role in the pathogenesis of idiopathic dystonia remains to be determined. PMID- 1449250 TI - Neuropsychological features of familial Alzheimer's disease. AB - It has been proposed that early-onset familial Alzheimer's disease (FAD) and sporadic Alzheimer's disease (AD) have different causes, with FAD due to a single dominant gene with disease onset before the sixth decade, whereas sporadic AD has a later onset and is not associated with a dominant pattern of inheritance. Given these differences, we questioned whether these etiologically distinct forms of AD also differ neuropsychologically. In this study we performed neuropsychological evaluations on patients from two well-documented families with FAD and a group of patients with sporadic AD. The groups were matched on global disease severity at entry. Two groups of education- and age-matched normal controls were recruited for comparison. The groups were analyzed for psychometric findings and pattern of deficits. Both patients with FAD and patients with sporadic AD showed a similar pattern of neuropsychological impairment relative to age-matched controls, i.e., mildly to moderately impaired verbal performance and concentration, severely slowed psychomotor speed, and severely impaired delayed recall of verbal material. There were no differences in pattern suggestive of disproportionately severe anomia, amnesia, agnosia, or apraxia in the early onset FAD group, as has been reported previously. PMID- 1449251 TI - Neurological rehabilitation. AB - Increasingly, neurologists are participating in the rehabilitation of disorders of the nervous system. Compelling reasons why neurologists, especially those with academic interests, should become involved in rehabilitation include the opportunity to observe patients in the recovery phases of their illnesses and to study issues relating to functional recovery, exposure to patients (such as those with spinal cord injury) who are often not seen by neurologists in the acute phase, and the opportunity to help establish a scientific base for rehabilitation medicine. Many areas of investigation can contribute to the scientific basis of neurological rehabilitation. Among the most promising are regeneration in the central (CNS) and peripheral nervous systems, adaptive mechanisms following CNS injury, computational neuroscience, neuromuscular physiology of chronic denervating conditions (e.g., the post-polio syndrome), and outcome studies of both physical and pharmacological therapeutic modalities. While there may be financial advantages to involvement in neurological rehabilitation, these are probably overestimated and interest in this field would continue to grow without them. There is a need for enhanced training in this subspecialty, including the development of dual certification programs in neurology and rehabilitation medicine. PMID- 1449252 TI - Dopamine D1 and D2 receptors in progressive supranuclear palsy: an autoradiographic study. AB - Dopamine D1 and D2 receptors were studied in brain tissue sections from a typical patient with progressive supranuclear palsy and in 7 age-matched brains. The density of D1 receptors in the caudate-putamen and frontal cortex of the patient was within control limits. By contrast, the density of nigral D1 receptors and striatal D2 receptors was dramatically reduced in the patient as compared to the control brains. This work shows again that the loss of striatal D2 receptors is the most plausible explanation for the poor response to dopaminergic drugs in patients with progressive supranuclear palsy. While the loss of nigral D1 receptors can be explained by the loss of nigral neurons, it seems that neurons bearing striatal D1 receptors are spared in progressive supranuclear palsy. The clinical effects of selective D1 agonists are worth testing in this devastating disorder. PMID- 1449253 TI - Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene. AB - The genetic mutation of X-linked recessive bulbospinal neuronopathy is amplification of a polymorphic tandem CAG repeat in the androgen receptor gene. We studied this CAG repeat in 26 Japanese patients from 21 families with X-linked recessive bulbospinal neuronopathy. The number of CAG repeats was significantly correlated with the age at onset of limb muscular weakness (r = -0.596, p < 0.001) and age-adjusted scored disability (r = 0.446, p < 0.03). The length of the CAG repeat therefore seems to be a determinant factor of clinical severity. PMID- 1449254 TI - Morton Prince. PMID- 1449255 TI - Prevalence of multiple sclerosis. PMID- 1449256 TI - Prevalence of multiple sclerosis. PMID- 1449257 TI - Prevalence of multiple sclerosis. PMID- 1449258 TI - [Non-Hodgkin's lymphoma and AIDS: histopathologic features]. AB - HIV-related non-hodgkin lymphomas currently occur in 5 to 8% of AIDS patients. AIDS-related lymphomas are high-grade tumors with the morphologic characteristics of either small noncleaved cell lymphomas of the Burkitt type or large cell centroblastic and immunoblastic lymphomas. Mixed features may be found, making classification difficult. Useful methods for characterizing AIDS-related non hodgkin's lymphomas include immunophenotypic studies using B-cell differentiation and activation antigens (HLA-DR, CD10, CD19, CD20, CD21, CD22, CD23, CD38), evaluation of expression of surface immunoglobulins (IgS), activation and proliferation (CD25, CD30, CD71, Ki67), and identification of T-cell markers (CD1, CD2, CD3, CD4, CD5, CD7, CD8). Cases studied were of the B-cell type. Comparison with morphologic features revealed that Burkitt's lymphomas were monoclonal and expressed B-cell markers (CD10, CD19, CD20, CD22, CD38) and surface immunoglobulins, especially IgM kappa. This immunophenotype is similar to that of large cell or centroblastic non-hodgkin's lymphomas, suggesting that Burkitt lymphomas originate from centrofollicular cells. Immunoblastic non hodgkin's lymphomas were monotypic or polytypic and expressed CD10 and CD38 antigens but not the other B-cell antigens Furthermore, a very large number of cells stained positively with the Ki67 antibody demonstrating that most lymphoma cells were undergoing cycling. PMID- 1449259 TI - [Large cell lymphomas: effect of histologic groups on the prognosis. Study of 210 cases treated with the same therapeutic protocols]. AB - As part of a study of two therapeutic protocols initiated in 1982 and 1985, respectively, for localized (n = 134) and disseminated (n = 76) large cell lymphomas, histologic type was determined for each patient by several pathologists using the Kiel classification for morphologic features and the international working formulation for protocol assignment and multifactorial statistical analysis. Therapeutic results in the two hundred and ten cases were correlated with a number of prognostic factors including age, stage, tumor size, extranodal disease, and clinical or biological markers for disease activity such as the LDH level. The previously reported influence of histologic subgroup on prognosis was not found with these highly effective protocols, whether histologic type was considered alone or in combination with other prognostic factors. The only consistent finding was that anaplastic large cell lymphomas, despite their aggressive features, were most likely to have a favorable outcome. PMID- 1449260 TI - [Signet ring cell tumor of the thyroid gland. Morphologic, immunohistochemical and ultrastructural study of a case and review of the literature]. PMID- 1449261 TI - [AIDS-related progressive multifocal leukoencephalopathy limited to U fibers, responsible for subacute encephalopathy with normal CT scan findings]. AB - A 41-year-old male homosexual with AIDS was hospitalized for temperature elevation to 40 degrees C with confusion. Neurologic evaluation found psychomotor slowing and temporospatial disorientation with no focal signs. The CD4 count was 100/mm3. CSF analysis and the CT scan were normal. Despite antiviral treatment the patient died fifteen days after admission. Gross appearance of the brain was normal. Histologic examination disclosed multiple, small foci of demyelination characteristic of progressive multifocal leukoencephalopathy. These foci were disseminated among the U fibers. In situ hybridization and immunocytochemical studies demonstrated papovavirus particles in oligodendrocytes and a few astrocytes. This case shows that papovavirus infection in AIDS patients may be responsible for a diffuse febrile encephalopathy with normal CT scan findings and a rapidly progressive course. PMID- 1449262 TI - [Keratosis of the oral cavity]. AB - Among white lesions of the oral cavity, keratoses can be suspected clinically but should be confirmed by histologic studies. Only examination under the microscope can demonstrate superficial keratinization of the epithelium. Irritative keratosis, dysplastic and malignant keratoses, and specific clinico-pathologic keratoses are reviewed successively. The differential diagnosis of white lesions of the oral cavity is discussed. PMID- 1449263 TI - [Necrotizing sialometaplasia]. AB - Necrotizing sialometaplasia is an infrequent, nonmalignant, self-limited condition involving the accessory salivary glands. Clinical and histologic features of necrotizing sialometaplasia may mistakenly suggest malignant disease. This fact emphasizes the importance of carefully correlating clinical and pathologic findings and of looking for histologic criteria indicative of nonmalignant disease. Three cases are discussed and the relevant literature is reviewed. PMID- 1449264 TI - [Rare lesion of the vulva]. PMID- 1449265 TI - [Heart-lung transplantation. A necropsy study of thirty-seven patients]. AB - Between 1987 and 1992, thirty-seven heart-lung transplant recipients had a postmortem examination at the Pitie-Salpetriere Teaching Hospital in Paris, France. Except for three patients who survived 2 months, 4 months and 16 months after transplantation, respectively, most patients died in the early postoperative period (mean survival time = 34.6 days). Autopsy disclosed minor acute heart rejection in four patients and minor acute lung rejection in three patients. Five patients had obliterating bronchiolitis that was the cause of death in two cases. Main causes of death included perioperative pleural bleeding, respiratory infection with or without septicemia, diffuse alveolar lesions (adult respiratory distress syndrome and/or pulmonary edema undergoing organization) and multiple organ failure. Hemodynamic and respiratory complications responsible for multiple organ failure in the perioperative period, as well as pre-existing morbid conditions such as cirrhosis of the liver induced by heart failure, may have a major bearing on the outcome of heart-lung transplantations. PMID- 1449266 TI - [Polymorphous low-grade adenocarcinoma of the minor salivary glands. Seven cases]. AB - Seven cases of polymorphous low-grade adenocarcinoma of the minor salivary glands are reported. This fairly recently described tumor, which is not exceptional, is characterized by a polymorphous architecture, fairly uniform cytologic features, and a marked tendency to infiltrate neighboring structures with perineural spread in virtually every case. Immunohistochemical and ultrastructural studies reported in the literature have demonstrated that the tumor cells exhibit epithelial and myoepithelial differentiation. These tumors probably arise from reserve cells in terminal ducts. The histologic study should eliminate two other tumors that carry a very different prognosis, i.e., pleiomorphic adenoma and the tubular, cribriform variety of cystic adenoid carcinoma. Low-grade polymorphic adenocarcinomas grow slowly. Recurrences are infrequent. Metastases are rare and involve only regional lymph nodes. The morphologic features and course of these tumors explain the term "low-grade polymorphous adenocarcinoma" used to designate them. PMID- 1449267 TI - Cancer morbidity and mortality in USA Mormons and Seventh-day Adventists. AB - Comparison of cancer morbidity and mortality rates between Mormons and Seventh day-Adventists and the corresponding rates in the Federal Republic of Germany and the United States, reveals that mortality from malignant neoplasms in general is much lower in Mormons and Seventh-day Adventists than in the Federal Republic of Germany. The difference concerns in particular the tobacco-dependent tumors: compared to the rate of affected males in the Federal Republic of Germany, only some 25% of Mormon males are getting lung cancer. Similar patterns are found in laryngeal carcinoma. Tumors that are related to both alcohol and tobacco, such as carcinomas of tongue, pharynx and esophagus, are also significantly less frequent in Mormons. Malignant neoplasms of the female genital tract show distinct analogies: cervical carcinoma has a morbidity rate of only 26.7% of affected women in Germany. Accordingly, mortality rates of Mormons and Seventh-day Adventists show a significant lower level when compared with cancer data of lung, colon and rectum, and prostate from the best German cancer registry (Saarland). Some tumor rates are higher in Mormons, e.g. malignant melanoma, also all types of malignant lymphoma and myeloma. The life expectancy is generally elevated by 2 4 years in Mormons and Seventh-day Adventists. The association with the particular life style of both religious groups, especially the strict reduction of tobacco consumption, and factors of dietary and other habits is discussed. PMID- 1449268 TI - Immunoreactivity of calmodulin, S-100 protein alpha and beta subunits in rat submandibular glands. AB - The calcium-binding proteins calmodulin and S-100 protein alpha and beta subunits were studied in Rat submandibular salivary gland using monoclonal antibodies and immunoperoxidase staining. Histologically, Rat submandibular gland consists of acinar and ductal components. The latter include intercalated, granular convoluted tubule, striated and excretory ducts. Ultrastructural studies of adult Rat granular convoluted tubule show granular cells, pillar cells and transition cells. Immunostaining for S-100 alpha and calmodulin was observed in granular convoluted tubule pillar cells and transition cells, whereas cells of striated ducts and intercalated ducts stained positive for calmodulin. S-100 beta staining in acinar cells was visible as a fine granular pattern. Although immunohistochemical localization in rat submandibular gland differed for S-100 alpha and beta subunits, expression was similar for S-100 alpha and calmodulin in the granular convoluted tubule segment. No immunodeposition of calmodulin, S-100 alpha or S-100 beta was found in granular cells, which contain growth factors such as EGF and NGF. PMID- 1449269 TI - [Oncogenes and tumor-suppressor genes]. AB - Tumors arise as a result of a chain of genetic alterations that impair normal cell functions and lead to invasion and development of metastases. These genetic alterations may result either in qualitative or quantitative changes in genes that play a key role in normal cell function, called proto-oncogenes, or in inactivation of genes that normally inhibit cell growth, called tumor suppressor genes. Whatever the mechanism involved, responses of the cell to changes in the environment become inappropriate. This paper successively reviews the various categories of proto-oncogenes, the mechanisms by which proto-oncogenes can be activated, and several examples of tumor suppressor genes. The various genetic factors involved in cell transformation probably act together to create a network of molecular interactions that results in tumor progression. PMID- 1449270 TI - A new model for testing gametocytocidal effects of some antimalarial drugs on Plasmodium falciparum in vitro. AB - A technique is described for obtaining pure gametocyte cultures of Plasmodium falciparum, using pyrimethamine at the minimum concentration for inhibition of asexual parasites. Routine cultures producing sexual stages were exposed to pyrimethamine on days 5 and 6. These cultures grew synchronously and contained gametocytes of stages II, III and V on day 7, 9 and 15 of the cultures respectively. The pyrimethamine-treated gametocytes were more infective to mosquitoes than were untreated controls. This model for the culture of pure gametocytes was used to observe the activity of chloroquine, halofantrine, pyrimethamine and quinine on the gametocyte stage III of Plasmodium falciparum strain NF54 in vitro. NF54 was shown to be sensitive to chloroquine, quinine and pyrimethamine, but the results showed that halofantrine was the most effective drug in reducing the number of gametocytes. A concentration of 3 x 10(-9) M halofantrine was lethal to both asexual parasites and gametocytes. The gametocytocidal EC90 of chloroquine (1 x 10(-6) M) and that of quinine (9 x 10( 7) M) were equal to the minimum inhibitory concentration of asexual stages of isolates of P. falciparum considered as highly resistant to these drugs. A high concentration of pyrimethamine (1 x 10(-4) M) had, in contrast, little effect on gametocytes. PMID- 1449271 TI - Malaria parasitological indices in the Cordillera Province (Santa Cruz Department, Bolivia). AB - In 1988-1989, as part of a co-operative programme with the local Unidad Sanitaria, two cross-sectional surveys were carried out to study the prevalence of malaria in eight villages in the rural areas near Camiri, Boyuibe and Gutierrez (Cordillera Province, Santa Cruz Department, Bolivia). Thick and thin blood films were collected from all available two- to nine-year-old children at the end of the dry season, in the first survey (252 samples), and after the rainy season, in the second survey (346 samples). The parasite and gametocyte indices increased between surveys from 1.59-25.72 and from 0.40-1.73, respectively. All infections were due to Plasmodium vivax. Both prevalence and parasite load were lower in children aged two to four years than in older children. Prevalences, parasite loads, and parasite densities were highest in rural areas near Camiri and Gutierrez. PMID- 1449272 TI - Oxido-reductive functions of Entamoeba histolytica in relation to virulence. AB - Entamoeba histolytica can reduce nitro-blue tetrazolium (NBT) in Hank's balanced salt solution to almost the same extent as in Eagle's minimal medium. Further, this reduction was stimulated only to a minor degree by glucose, pyruvate and DL serine, substrates known to support respiratory activity (O2 uptake) in E. histolytica. However, both NADH and NADPH increased NBT reduction several-fold, the effect being greater with NADPH. A sizeable proportion of this endogenous dye reducing capability (in Hank's solution) was associated with low-speed sediments obtainable from amoebic homogenates, which also shared the bulk of 125I labelling (when the homogenates were prepared after surface labelling with Na 125I). Conversion of the dye to formazan was strongly inhibited by -SH blocking agents, but was not influenced by rotenone and antimycin A. The activity was also inhibited by H2O2, but stimulated by catalase. Superoxide dismutase only slightly curtailed NBT reduction in intact cells, but inhibited it in homogenates in a concentration-dependent manner to a maximal extent of 33%. Almost the same degree of curtailment of this activity was induced by anaerobic conditions. Both concanavalin A (Con A) and phorbol myristate acetate stimulated the activity in intact cells, though the effect of Con A was nullified by alpha-methyl mannoside. Both NBT-reducing capability and alcohol dehydrogenase activities were higher in the more virulent IP:106 strain, and they increased with time in cultures of NIH:200 in a cholesterol-enriched environment. PMID- 1449273 TI - The efficacy of chemotherapy with mebendazole in human cystic echinococcosis: long-term follow-up of 52 patients. AB - Sixty patients with Echinococcus granulosus infection of the liver, lungs, bone and/or soft tissues were treated for several months with oral mebendazole (50-60 mg kg-1 day-1), in divided doses after fat-rich meals, either without surgery (WS), post-surgery (PS) or pre- and post-surgery (PPS). Long-term follow-up, possible for 52 of the patients, showed that WS, PS and PPS patients have so far remained disease-free following treatment for (means +/- standard deviations) 65.5 +/- 37.7, 82.5 +/- 37.0 and 84.1 +/- 28.3 months, respectively. Ultrasound and computed tomography scans were similar in WS and PPS patients post-treatment. Blood eosinophil levels, which were sometimes elevated initially, returned to normal in all patients and this decrease indicated cyst degeneration before this was evident on the scans. Treatment of patients with cystic echinococcosis may no longer require surgery. PMID- 1449274 TI - Antibodies of different immunoglobulin isotypes in serum and bile of patients with clonorchiasis. AB - Specimens of serum and bile from patients were assayed by an enzyme-linked immunosorbent assay to reveal antibodies specific to antigens from adult Clonorchis sinensis. Antibodies of the IgG isotype showed the greatest elevation during infection (Student's t-test, P < 0.001), whereas serum IgA and IgE and secretory IgA in bile were moderately elevated (P < 0.05). Major differences in the distribution of antibodies among the IgG subclasses were observed between patients who were and those who were not infected. IgG4 antibody levels were elevated in the serum and bile of infected patients, and there were significant correlations between the levels of IgG and IgG4 antibodies and the intensity of infection. PMID- 1449275 TI - Ivermectin for the treatment of periodic malayan filariasis: a study of efficacy and side effects following a single oral dose and retreatment at six months. AB - Ivermectin, a new antifilarial drug and currently the drug of choice for the treatment of onchocerciasis, has been shown to be effective in bancroftian filariasis. We report here, for the first time, the efficacy and safety of the drug in the treatment of filariasis caused by periodic Brugia malayi. Sixty male, asymptomatic microfilaraemics of Alleppey district, Kerala, South India, received single oral doses of ivermectin in a double blind study. Four dosages were used: 20, 50, 100 and 200 micrograms kg-1 body weight. Clearance of microfilariae, which was not complete, began as early as 12 hours post-treatment and was maximal at the end of one month. Microfilaria levels began to rise thereafter and reached 20-50% of pretreatment levels at six months. The two higher doses (100 and 200 micrograms kg-1) were more effective in suppressing microfilaraemia at six months (P < 0.05). After six months, 32 patients were retreated using the same dose of ivermectin that they had received initially. The pattern of clearance was essentially similar to that seen during the first treatment phase and microfilaria levels were 10-35% of pretreatment levels at the end of the next six months. Twenty-eight individuals who were not retreated at six months continued to have increasing levels of microfilariae, reaching 60% of pretreatment levels at the end of the next six months. Side effects (such as fever, headache, myalgia), which were mild to moderate, were seen in most patients and were unrelated to the dose (P > 0.05) or pretreatment levels of microfilariae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449276 TI - The prevalence and intensity of soil-transmitted helminthiases in rural communities in southern Nigeria. AB - An investigation of the prevalence and intensity of soil-transmitted helminthiases was undertaken in four villages in Oyo state, Nigeria. Diagnosis was based on examination of stool samples for the presence of helminth ova in all age classes. The prevalence of Ascaris lumbriocoides ranged from 61.5-72.2%, of Trichuris trichiura from 65-74%, and of hookworm from 52.4-63% depending on the village concerned. Intensity, assessed indirectly as the mean eggs per gram of faeces (epg), varied with regard to the four villages. The mean egg count of A. lumbricoides varied from 6815-10,823 per gram, of T. trichiura from 127-246, and of hookworm from 122-267. Host age, sex and household size were found to be significant factors influencing faecal egg output, and indirect measure of the intensity of the helminth infections. PMID- 1449277 TI - Human Oesophagostomum infection in northern Togo and Ghana: epidemiological aspects. AB - Recently, it has been established that human infection with Oesophagostomum bifurcum is common in northern Togo and northeastern Ghana. Two surveys were conducted in this area. In a regional survey, O. bifurcum infection appeared to occur in 38 of 43 villages. The highest prevalences (up to 59%) occurred mostly in small isolated villages and were usually associated with high hookworm infection rates. The infection was relatively rare in children under five years of age (7% infected). In older individuals, females showed higher prevalences than males (30% vs. 24%). In a second survey, the entire population of two high prevalence villages was examined. Infection rates were low in children under three years of age, but rose quickly thereafter, suggesting intense transmission. A stable level of infection was reached by 10 years of age. Oesophagostomum larvae were found more frequently in hookworm-positive than in hookworm-negative coprocultures, and possible explanations for the association between infection with Oesophagostomum and hookworm are discussed. PMID- 1449278 TI - Coagulation abnormalities and ivermectin. AB - Prothrombin ratios were measured 13-16 days after treatment in 148 subjects from Sierra Leone taking part in a double-blind placebo-controlled trial of ivermectin. Prolonged prothrombin ratios were observed more frequently in the ivermectin group, although this difference was not significant and no patients suffered bleeding complications. Further investigation of these patients failed to reveal any abnormality of liver function, although factor VII and II levels were reduced in most affected individuals, suggesting interference with vitamin K metabolism. Ivermectin has a minimal effect on coagulation and concern about mass treatment for this reason appears to be unjustified. PMID- 1449279 TI - Plasmodium ovale in the highlands of Irian Jaya, Indonesia. PMID- 1449280 TI - Comparison of Leishmania infections in sandflies fed with two types of feeders. PMID- 1449281 TI - A possible animal reservoir for Leishmania tropica s.l. in Kenya. PMID- 1449282 TI - The seroprevalence of toxoplasmosis in sheep, goats and pigs in Zimbabwe. PMID- 1449283 TI - Experimental infection and morphology of Taenia saginata (Burma strain) in domestic animals. PMID- 1449284 TI - Mediastinitis in heart transplantation. AB - Between March 1985 and December 1991, mediastinitis developed in 12 of 420 cardiac transplantation patients (2.8%). The mortality rate in this group of patients was 8.3% (1/12). Actuarial survival (1 year, 75%; and 5 years, 65%) was not significantly different from that of the group without mediastinitis (1 year, 88%; and 5 years, 75%). A higher percentage of the patients in the group with mediastinitis were listed as UNOS status 1 (50% versus 35%) and had a history of previous sternotomies (58% versus 44%). The presentation of mediastinitis was typical. Computed tomographic scanning with or without aspiration was a valuable adjunct in the diagnosis of mediastinitis. Induction immunotherapy with minimal steroids in the perioperative period was used in all patients. This may contribute to the patients' ability to mount an appropriate and effective response to infection, permitting earlier diagnosis. The debridement irrigation technique used in 8 of 12 patients had a low success rate of 33%, whereas the debridement muscle flap technique used in 4 of 12 was 100% successful in eliminating infection. PMID- 1449285 TI - Long-term effect of total fundoplication on the myotomized esophagus. AB - From 1978 to 1983, 17 patients had an esophagocardiomyotomy with an added short total fundoplication as an antireflux procedure. Thirteen had achalasia and 4, diffuse esophageal spasm. All patients initially had the usual symptoms of these motor disorders. Early after the operation all became asymptomatic, but over the years of follow-up, symptoms reappeared in 14 of 17 patients, and 5 required reoperation. The distal esophageal transverse diameter showed progressive dilatation from 3.9 cm preoperatively to more than 6 cm after 10 years of evolution. Over the same period, deterioration in the esophageal emptying capacity caused esophageal stasis to increase from 32% to 75%. Manometric changes were significant after the operation: resting pressures in the esophageal body decreased from 10.5 to 4.4 mm Hg (p < 0.001) proximally and from 12.2 to 4.6 mm Hg distally (p < 0.001). Peak contraction pressures became significantly weaker: 38 to 30 mm Hg in the proximal esophagus (p < 0.001) and from 49.2 to 28.1 in the distal esophagus (p < 0.001). Tertiary contractions were unchanged distally, but peristalsis reappeared in more than 30% of all swallows in the proximal half of the esophageal body. The resting pressure gradient in the lower esophageal sphincter area was reduced from 25.5 to 7.4 mm Hg by the operation. This gradient remained stable over 10 years of follow-up. No significant acid exposure was documented in 8 patients undergoing 24-hour pH recordings after their operation. Endoscopy revealed dilatation and retention without evidence of reflux esophagitis damage. Total fundoplication when associated with esophageal myotomy results in improved symptoms in the early postoperative phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449286 TI - Clinical manifestation of mediastinal fibrosis and histoplasmosis. AB - We treated 20 patients thought to have mediastinal fibrosis secondary to Histoplasma capsulatum. All but 1 were symptomatic. The most common symptoms were dyspnea (8), hemoptysis (6), postobstructive pneumonia (5), and superior vena caval obstruction (2). Nine patients had severe stenosis of the trachea, carina, or main bronchus. Special stains identified Histoplasma capsulatum in surgical specimens in 9 patients. Surgical procedures were done for 18 of 20 patients (resection of subcarinal mass, 6; right middle and lower lobectomy, 5; carinal pneumonectomy, 4; esophagoplasty, 4; sleeve resection, 3 (with right main bronchus in 1, right lower and middle lobectomy in 1, and carina in 1); right upper lobectomy, 1; middle lobectomy, 1; and bronchoplasty of left main bronchus, 1. There were 4 deaths, 3 after complications of carinal pneumonectomy and 1 in a patient with tracheobronchial obstruction that could not be dilated. Two patients were treated with amphotericin and 4 with ketoconazole. Sclerosing mediastinitis secondary to histoplasmosis presents tremendous surgical challenges because of the intense fibrosis encountered. Bronchoplastic procedures are possible in spite of the intense fibrosis. High mortality rates after carinal resection may be encountered. The exact role of antifungal therapy is as yet undefined. PMID- 1449287 TI - Postcardiotomy centrifugal mechanical ventricular support. AB - From August 1979 through August 1991, 91 patients were supported with centrifugal mechanical ventricular assist. Major indications for its use were postcardiotomy ventricular failure (79) or as a bridge to cardiac transplantation (12). In postcardiotomy use (0.2% of all cardiac procedures), there were 54 male (68.4%) and 25 female patients (31.6%) with a mean age of 54.8 years and a mean duration of use of 3.56 days (range, 1 hour to 19 days). Forty-nine patients (62%) were successfully weaned, and 20 (25.3%) were hospital survivors. In 57 patients the device was inserted to wean from cardiopulmonary bypass, whereas in 22 it was employed later in the postoperative period because of low cardiac output or sudden arrest. Thirty-four (59.6%) of the 57 patients in the former group were weaned, and 15 (26.3%) were discharged, results similar to those in the latter group with 15 (68.2%) weaned and 5 (22.7%) discharged. Morbidity associated with use of centrifugal blood pumps included bleeding (87.3%; mean transfusion requirement, 53.2 units), renal failure (46.8%), cerebrovascular accident (12.7%), thromboembolism (12.7%), and hepatic insufficiency (12.7%). After a mean follow-up of 45.4 months (range, 2 to 142 months), 7 patients had died (35% late mortality), 1 patient is in functional class IV, and all others are in functional class I or II. Lower survival was associated with biventricular failure and renal failure but not with age or sex of the patient. PMID- 1449288 TI - Device-supported myocardial revascularization: safe help for sick hearts. AB - Although advances in both the technology of artificial oxygenation and our understanding of myocardial preservation have made aortocoronary bypass operations safer, clinical settings remain where even these improvements have limited efficacy. We have recently treated 43 severely ill patients with aortocoronary bypass, using a ventricular assist device for intraoperative hemodynamic support and ventricular decompression. For 34 of the patients, preoperative ejection fractions (multigated acquisition) ranged from 0.12 to 0.28 (average, 0.22); 6 patients manifested cardiogenic shock preoperatively, and emergency operations precluded multigated acquisition studies. Twenty-nine patients had preoperative evidence of congestive heart failure, 10 had a prior bypass operation, 9 had major chronic obstructive pulmonary disease, and 2 were Jehovah's Witnesses. The operative technique involved minimal doses of heparin (1 to 1.5 mg/kg), no cardioplegia, and no cardiopulmonary bypass. Revascularization was accomplished on beating, nonworking hearts, with right (40 of 43) and left (43 of 43) ventricles supported by Nimbus Hemopumps (4 of 43) or Bio-Medicus centrifugal ventricular assist devices for an average of 112 minutes. In each case, the patient's lungs were used as the oxygenator. An average of 3.7 bypass grafts per patient were constructed. The left internal mammary artery was used in 41 patients, whereas at least one coronary endarterectomy was required in 20. Six patients had concomitant placement of an automatic implantable cardioverter defibrillator. Two patients (4.6%) died: 1 (with preoperative cardiogenic shock) of low cardiac output on postoperative day 1, and 1 of a severe neurologic deficit on day 8. Follow-up ranged from 2 to 18 months (average, 8.9 months), with all survivors demonstrating improvement in cardiac function in both the early and late postoperative periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449289 TI - Early cellular events in the lung allograft. AB - We hypothesized that ischemic insult to the lung allograft may render it more susceptible to rejection. Left canine single-lung allografts were subjected to usual periods of cold and warm ischemia (4 hours and 1 hour, respectively). Bronchoalveolar lavage and open lung biopsies were performed at 0, 1, 4, and 24 hours and 1 week after transplantation. Bronchoalveolar lavage fluid was examined for cellular phenotypes, lymphocyte lectin-mediated cytotoxicity, and natural killer cell cytotoxicity. Open lung biopsy specimens were examined for severity of injury/rejection and MHC class II expression. Within 1 to 4 hours of reimplantation, we observed marked influx of polymorphonuclear leukocytes and lymphocytes and an increase in lectin-mediated cytotoxicity (25.6% +/- 14.8% and 50.6% +/- 20.1% versus 5.4% +/- 7.5% preoperatively; p < 0.05). In addition, natural killer cell cytotoxicity increased from 10.2% +/- 13.5% before transplantation to 20.5% +/- 8.6% 4 hours after transplantation (p < 0.03). By 24 hours MHC class II expression became evident and continued to increase while subtle histologic evidence of rejection appeared by 1 week. We conclude that ischemia-reperfusion injury can alter the local bronchopulmonary milieu, thus rendering it more susceptible to the development of rejection. PMID- 1449290 TI - Bioassay of EDRF from internal mammary arteries: implications for early and late bypass graft patency. AB - To study the basal, luminal release of endothelium-derived relaxing factor, 35-mm segments of canine internal mammary artery (IMA) were cannulated and perfused at 5 mL/min in vitro with physiological salt solution. Vasoactive properties of the effluent were bioassayed on coronary artery smooth muscle. Effluent from IMAs produced significant vasodilation of the bioassay ring compared with effluent from a prosthetic conduit (n = 24; p < 0.05). The vasodilation by the effluent could be eliminated by mechanically removing the intima of the IMA, or by treating the IMA segments with NG-monomethyl-L-arginine or NG-nitro-L-arginine, two competitive inhibitors of nitric oxide synthesis from L-arginine; vasodilation was not influenced by treatment with indomethacin. In 83% of the superfusion experiments, effluent from the left IMA induced greater relaxation of the bioassay ring than did effluent from the right IMA. In addition, the average vasodilation induced by left IMA effluent was 28% +/- 2.3% versus 17.4% +/- 3.1% for the right (n = 24; p < 0.05). However, in organ chamber experiments, right and left IMAs exhibited comparable endothelium-dependent vasodilation to acetylcholine (n = 6). Because endothelium-derived relaxing factor induces vasodilation and also inhibits platelet adhesion, platelet aggregation, and atherogenesis, luminal release of endothelium-derived relaxing factor by the IMA could contribute to superior results when the artery is used in bypass grafting. PMID- 1449292 TI - Left atrial isolation associated with mitral valve operations. AB - Surgical isolation of the left atrium was performed for the treatment of chronic atrial fibrillation secondary to valvular disease in 100 patients who underwent mitral valve operations. From May 1989 to September 1991, 62 patients underwent mitral valve operations (group I); 19, mitral valve operations and DeVega tricuspid annuloplasty (group II); 15, mitral and aortic operations (group III); and 4, mitral and aortic operations and DeVega tricuspid annuloplasty (group IV). Left atrial isolation was performed, prolonging the usual left paraseptal atriotomy toward the left fibrous trigone anteriorly and the posteromedial commissure posteriorly. The incision was conducted a few millimeters apart from the mitral valve annulus, and cryolesions were placed at the edges to ensure complete electrophysiological isolation of the left atrium. Operative mortality accounted for 3 patients (3%). In 79 patients (81.4%) sinus rhythm recovered and persisted until discharge from the hospital. No differences were found between the groups (group I, 80.7%; group II, 68.5%; group III, 86.7%; group IV, 75%; p = not significant). Three late deaths (3.1%) were registered. Long-term results show persistence of sinus rhythm in 71% of group I, 61.2% of group II, 85.8% of group III, and 100% of group IV. The unique risk factor for late recurrence of atrial fibrillation was found to be preoperative atrial fibrillation longer than 6 months. Due to the satisfactory success rate in recovering sinus rhythm, we suggest performing left atrial isolation in patients with chronic atrial fibrillation undergoing valvular operations. PMID- 1449291 TI - Coronary artery bypass without cardiopulmonary bypass. AB - The purpose of this article is twofold: to describe our technique for performing coronary artery bypass grafting without cardiopulmonary bypass (off pump) and to demonstrate that this operation is safe, in terms of mortality and certain indices of morbidity. Very little has been published in regard to off-bypass operations. From 1985 through 1990, 220 patients underwent operation off bypass; 220 on-pump controls were retrospectively matched for number of grafts, left ventricular function, and date of operation. Groups were compared in terms of mortality and ten indicators of morbidity. The same analysis was performed for ten subgroups. We found no statistically significant difference between groups in mortality (off pump, 1.4% [3/220]; on pump, 2.4% [5/220]), which held across all subgroups. Patients undergoing operation off pump required blood far less often (not transfused: off pump, 72.7% [160/220]; on pump, 54.6% [116/220]; p = 0.005 by Fisher's exact test), and the low output state occurred statistically less frequently off pump (off pump, 5.5% [12/220]; on-pump, 12.7% [28/220]; p = 0.01 by Fisher's exact test). Further research should be directed to which subgroups can be operated on to advantage off pump and which, if any, groups of patients should be confined to on-bypass operations. PMID- 1449293 TI - Combined carotid and coronary revascularization: the preferred approach to the severe vasculopath. AB - The timing of carotid endarterectomy (CEA) and coronary revascularization (CABG) for concomitant disease is controversial. Results of combined CEA/CABG in 127 patients (age range, 46 to 82 years; mean age, 65 years; 61% male) from 1978 to 1991 were reviewed. Ninety-five patients (75%) were in New York Heart Association functional class III or IV, 48 (38%) had left main coronary artery disease, and 32 (28%) had depressed ejection fraction ( < 0.50). Forty (32%) had asymptomatic bruits, 61 (48%) transient ischemic attacks, and 26 (20%) prior strokes. Seventy five (59%) had bilateral carotid stenosis, including 20 (16%) with contralateral occlusions. Perioperative mortality was 7 of 127 (5.5%), and all deaths were cardiac related. Myocardial infarctions occurred in 6 of 127 patients (4.7%) and were nonfatal in 3 (2.3%). Permanent strokes occurred in 7 of 127 (5.5%) and were ipsilateral in 5 (3.9%). Perioperative stroke did not occur in the asymptomatic group, but the risk was higher in those with prior stroke (19%) or with contralateral carotid occlusion (15%). The stroke risk for our patients with carotid disease having CABG without CEA is not known, but the literature reports rates as high as 14%. For our patients without known concomitant disease, the risk of permanent stroke was 1.0% (31/3012) for isolated CABG and 1.5% (7/482) for isolated CEA. The late results after CEA/CABG revealed a 5-year survival of 70% +/- 5%, which correlated with ejection fraction ( > or = 0.50, 81% +/- 5%; < 0.50, 45% +/- 11%; p < 0.003). Freedom from late permanent ipsilateral stroke was 97% +/- 2% at 8 years. Freedom from stroke at 5 years was lower among patients with a previous stroke (71% +/- 10%) compared with transiently symptomatic (90% +/- 4%) and asymptomatic (96% +/- 4%) patients (p < 0.03). Combined CEA/CABG is a useful option in this high-risk group of patients with extensive atherosclerosis; avoids a subsequent hospitalization, anesthetic, and delay period; and provides long-term protection from ipsilateral stroke. PMID- 1449294 TI - Vascular anatomy of the gastric tube used for esophageal reconstruction. AB - This study investigates the actual, as contrasted with the presumed, blood supply of the greater curvature gastric tube commonly used to reconstruct the gullet after esophagogastrectomy. Arterial and venous corrosion casts of this tube were created in 30 cadavers and demonstrated the following: (1) The right gastroepiploic artery is the exclusive conduit of blood in the pedicle. (2) The contribution of the right gastric artery is negligible. (3) Although tributaries of the left gastroepiploic artery are distributed over the central portion of the tube, the connection between the right and left gastroepiploic vessels is minute. (4) The blood supply of the cranial 20% of the greater curvature tube is through a microscopic network of capillaries and arterioles. These findings constitute an anatomical argument for extremely gentle handling of the stomach throughout its mobilization, during construction and positioning of the tube, and during the anastomosis. PMID- 1449295 TI - Absent pulmonary valve syndrome: operation in infants with airway obstruction. AB - From 1979 through 1991, 19 infants with absent pulmonary valve syndrome and airway obstruction were seen for surgical treatment. All patients underwent extensive pulmonary artery aneurysmorrhaphy using cardiopulmonary bypass. Fourteen patients had simultaneous transatrial ventricular septal defect (VSD) closure, infundibular resection, and placement of a short transannular patch; 2 had transventricular VSD closure and infundibular resection without a transannular patch; 1 underwent transventricular VSD closure and transannular patching; and 2 underwent pulmonary artery aneurysmorrhaphy alone with the VSD left open. All 19 infants had good hemodynamics when taken from the operating theater, but 3 died postoperatively of severe airway obstruction, despite further tracheobronchopexy procedures in 2 (hospital mortality rate, 16%; confidence limits, 7% to 29%). Among the 16 patients discharged from the hospital, there was one late death. Five other patients have required reoperation for branch pulmonary artery stenosis (n = 2), residual airway obstruction resulting from persistent pulmonary artery dilatation (n = 1), closure of VSD (n = 1), and homograft valve insertion for pulmonary incompetence and right ventricular dysfunction (n = 1). There are 15 long-term survivors. Eight of them have episodic bronchospasm of mild to moderate severity, and all are responsive to sympathomimetic bronchodilator aerosols. The remaining 7 are asymptomatic. PMID- 1449296 TI - Effect of delay in retroperfusion therapy on infarct size reduction. AB - Retroperfusion of arterial blood through the coronary sinus reduces infarct size if therapy starts immediately after coronary artery occlusion. To determine if a new system of non-electrocardiogram-synchronized retroperfusion is able to reduce infarct size after delays consistent with clinical use, anesthetized pigs were subjected to 4 hours of left anterior descending coronary artery occlusion followed by 1 hour of reperfusion. Retroperfusion of arterial blood commenced immediately after occlusion of the left anterior descending coronary artery in the no-delay group (n = 10) and after a 1-hour (n = 10) and a 2-hour (n = 8) delay in two other groups. In the control group (n = 10), no therapy was used. In all groups, retroperfusion of arterial blood was terminated after 4 hours of occlusion of the left anterior descending coronary artery. Infarct size, expressed as a percentage of the in vivo area at risk (+/- the standard deviation), was smaller in the no-delay group (44.1 +/- 12.9) and marginally smaller in the 1-hour delay group (71.0 +/- 9.8) compared with controls (86.3 +/- 7.5) (p < 0.05). Infarct size in the 2-hour delay group (75.0 +/- 10.7) was not significantly different from controls. Mean coronary sinus pressure (+/- the standard deviation) was 56 +/- 25 mm Hg, 39 +/- 9 mm Hg, and 47 +/- 9 mm Hg in the no-delay, 1-hour delay and 2-hour delay groups, respectively. Thus, this new retroperfusion system limits infarct size by 50% if it is started immediately after coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449297 TI - Hyperglycemia increases cerebral intracellular acidosis during circulatory arrest. AB - Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess cerebral high-energy phosphate metabolism and intracellular pH in normoglycemic and hyperglycemic sheep during hypothermic circulatory arrest. Two groups of sheep (n = 8 per group) were placed in a 4.7-T magnet and cooled to 15 degrees C using cardiopulmonary bypass. Spectra were acquired before and during circulatory arrest and during reperfusion and rewarming. Intracellular pH and adenosine triphosphate levels decreased during circulatory arrest. Compared with the normoglycemic animals, the hyperglycemic group was significantly more acidotic with the greatest difference observed during the first 20 minutes of reperfusion (6.40 +/- 0.08 versus 6.08 +/- 0.06; p < 0.001). Intracellular pH returned to baseline after 30 minutes of reperfusion in the normoglycemic group but did not reach baseline until 1 hour of reperfusion in the hyperglycemic animals. Adenosine triphosphate levels were significantly higher in the hyperglycemic group during circulatory arrest. Repletion of adenosine triphosphate during reperfusion was similar for both groups. These results support the hypothesis that hyperglycemia during cerebral ischemia drives anaerobic glycolysis and thus leads to increased lactate production and an increase [corrected] in the intracellular acidosis normally associated with ischemia. PMID- 1449298 TI - Barbiturates impair cerebral metabolism during hypothermic circulatory arrest. AB - Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37 degrees C, during cardiopulmonary bypass before and after drug administration at 37 degrees C and 15 degrees C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37 degrees C followed by an infusion of 3.3 mg.kg-1 x min-1 until hypothermic arrest. A control group of animals (n = 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15 degrees C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p < or = 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain. PMID- 1449299 TI - Coronary sinus injuries during retrograde continuous normothermic blood cardioplegia. AB - Injuries to the coronary sinus during cardioplegic arrest are rare but potentially lethal. We herein present case reports of injuries to the coronary sinus occurring during retrograde continuous normothermic blood cardioplegia, and emphasize preventive measures and treatment. PMID- 1449300 TI - Clinical cardiomyoplasty: preoperative factors associated with outcome. AB - Dynamic cardiomyoplasty has been used clinically to augment the ventricular function of a failing heart. Fifteen clinical dynamic cardiomyoplasties have been performed at Allegheny General Hospital since 1985. Left ventricular ejection fraction improved in long-term survivors from a preoperative value of 0.23 +/- 0.02 to 0.32 +/- 0.05 with postoperative cardiomyostimulation (p < 0.05). There was an average reduction of 2 +/- 0.3 New York Heart Association classes (3.6 +/- 0.2 before operation versus 1.6 +/- 0.4 after operation; p < 0.001). Postoperative mortality was 27% (4/15), and early mortality (within 6 months after operation) was 20% (3/15). Significant preoperative differences between survivors and nonsurvivors were found in right ventricular ejection fraction (0.53 +/- 0.03 versus 0.30 +/- 0.07; p < 0.05), pulmonary artery mean pressure (19 +/- 2 versus 34 +/- 6 mm Hg; p < 0.05), pulmonary artery diastolic pressure (12 +/- 1 versus 25 +/- 5 mm Hg; p < 0.05), and pulmonary vascular resistance (1.4 +/- 2 versus 2.5 +/- 0.7 Wood units; p < 0.05). Dynamic cardiomyoplasty can be done with low operative mortality in patients with isolated left ventricular failure, but mortality is high in those with biventricular failure or pulmonary hypertension. Improvement in functional class and ventricular function can be expected in long-term survivors. Application of these findings to patient selection will improve the risk/benefit ratio for dynamic cardiomyoplasty. PMID- 1449301 TI - Fluosol cardioplegia results in complete functional recovery: a comparison with blood cardioplegia. AB - Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery. Fluosol is an asanguineous solution with the ability to bind and release oxygen linearly at low temperatures. Neonatal piglet hearts (24 to 48 hours old) were excised and supported on an isolated, blood-perfused working heart model. After baseline stroke-work index was determined, hearts were arrested with either normocalcemic blood cardioplegia (group 1, n = 8) or normocalcemic Fluosol cardioplegia (group 2, n = 8). Cold cardioplegia was administered at 45 mm Hg every 20 minutes for 2 hours. Hearts were then reperfused with whole blood. Functional recovery, expressed as percent of control stroke-work index, was determined 60 minutes after reperfusion at left atrial pressures of 3, 6, 9, and 12 mm Hg. Functional recovery at 60 minutes was similar between group 1 (95%, 93%, 93%, 88%) and group 2 (100%, 94%, 94%, 95%) at left atrial pressures of 3, 6, 9, and 12 mm Hg, respectively. Mean lactate consumption 5 minutes after reperfusion was significantly greater (p = 0.0001) in group 1 (31.8 +/- 6.3 micrograms.min-1 x g-1) than in group 2 (-0.59 +/- 0.1 microgram.min-1 x g-1), indicating superior metabolic recovery in the blood cardioplegia hearts. Edema formation, as determined both by water content (group 1, 81.10%; group 2, 81.63%) and by electron microscopy, was not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449302 TI - Influence of beta 1-blockade on myocardial substrates early after a coronary operation. AB - A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. This study was undertaken to find out if early postoperative high-dose infusion of the selective beta 1-blocking agent metoprolol tartrate has additional effects on metabolic variables related to myocardial energy supply/demand balance compared with those obtained with a late preoperative oral dose. The study included 21 male patients undergoing coronary bypass grafting. All patients received an oral dose of metoprolol before the operation. After the operation, patients were randomized to a control group or a group receiving intravenous infusion of metoprolol. Myocardial uptake of oxygen and substrates was determined before and during atrial pacing. Metoprolol reduced arterial concentrations of free fatty acids, reduced myocardial uptake of free fatty acids, and enhanced myocardial uptake of lactate. During paced tachycardia, the metoprolol concentration correlated negatively with myocardial uptake of free fatty acids (r = -0.80; p < 0.001) and positively with myocardial uptake of lactate (r = 0.53; p < 0.05). It is concluded that postoperative infusion of metoprolol induces myocardial metabolic changes compatible with an improved energy supply/demand balance. PMID- 1449303 TI - Pleuropulmonary aspergilloma: clinical spectrum and results of surgical treatment. AB - From 1974 to 1991, 77 patients were admitted for pulmonary (55), pleural (16), or bronchial (6) aspergilloma. About 50% were asymptomatic. Sixty-three underwent operation. Pulmonary aspergillomas were operated on for therapeutic need in 26 and on principle in 18; the procedures were 28 lobar or segmental resections, 10 thoracoplasties, and 5 pleuropneumonectomies (1 patient had exploration only). Pleural aspergillosis was treated by operation on principle in 5 and for therapeutic need in 8 patients; 10 thoracoplasties, 1 attempt at pleuropneumonectomy, and 2 decortications were performed. All six bronchial lesions were operated on as a rule. Overall postoperative mortality was 9.5%. Major complications were bleeding (n = 37), pleural space problems (n = 24), respiratory failure (n = 6), and postpneumonectomy empyema (n = 4). All patients with pleural disease experienced complications. The outcome was better after lobar or segmental resection than after thoracoplasty (mortality, 6% versus 15%). Asymptomatic and nonsequellary pulmonary or bronchial aspergilloma also had an improved outcome. We conclude that operation is at low risk in pulmonary or bronchial locations in asymptomatic patients and in the absence of sequellae; the risk is high in symptomatic patients for whom operation is the only definite treatment. Pleuropneumonectomy should be avoided. Only symptomatic pleural aspergilloma should be operated on. PMID- 1449304 TI - Temporary double exclusion of the perforated esophagus using absorbable staples. AB - A new method for double exclusion of the esophagus is presented. Temporary closure of the cervical and intraabdominal esophagus using absorbable staples allows effective healing of esophageal perforations. The procedure should be routinely combined with drainage of the periesophageal abscess. Complete recanalization of the esophagus occurs 1 to 2 weeks after operation. PMID- 1449305 TI - Vascular and interstitial effect of University of Wisconsin solution on canine lung. AB - Belzer's University of Wisconsin cold storage solution (UWCSS) has proved useful in extending the shelf life of organs in extrathoracic transplantation and more recently has also been shown to be useful in heart transplantation. I investigated the effect of 4 degrees C UWCSS on the vascular and interstitial properties of the lung to see whether it affected the pulmonary microcirculation or caused pulmonary edema. Infusion of UWCSS was associated with a slight decrease in oxygen tension, but the final oxygen tension was no different from that previously demonstrated with Euro-Collins solution. Vascular conductance was not affected by UWCSS, but average vascular closure increased slightly, indicating that increased vascular tone occurs. This effect is similar to but less than that previously observed with Euro-Collins solution. Based on comparisons of wet to dry weight ratios, estimates of interstitial compliance, transvascular fluid flux, and microvascular filtration coefficient, it does not appear that UWCSS causes pulmonary edema. Further investigation into the usefulness of UWCSS in lung transplantation is therefore warranted. PMID- 1449306 TI - Safety and efficacy of autologous blood donation before elective aortic valve operation. AB - Although the use of preoperative autologous blood donations for patients undergoing elective cardiac operations has increased dramatically in recent years, patients awaiting elective aortic valve replacement have traditionally been denied access to preoperative autologous blood collection programs. We report our experience with 79 patients, each of whom donated 1 to 3 units of autologous blood before an aortic valve operation. All patients had serious aortic valve disease as evidenced by symptoms and preoperative catheterization data. The patients collectively made 129 blood donations. One patient had a syncopal episode within 2 hours of donation and recovered without difficulty. Of the patients who gave autologous blood preoperatively, 68% avoided any homologous blood donor exposure during their subsequent hospitalization for aortic valve replacement. In contrast, in a group of 298 patients who did not give autologous blood preoperatively, only 31% avoided homologous blood exposure during aortic valve replacement (p < 0.0001). Our experience suggests that preoperative autologous blood donation by patients awaiting elective aortic valve replacement is both safe and effective. Patients with aortic valve disease should not be routinely excluded from preoperative blood services. PMID- 1449307 TI - Clinical and hemodynamic evaluation of the 19-mm Carpentier-Edwards supraannular aortic valve. AB - The clinical and hemodynamic performance of the 19-mm Carpentier-Edwards supraannular aortic valve is largely unknown compared with that of the larger valves. Over 4 years we implanted the 19-mm Carpentier-Edwards supraannular aortic valve into 21 patients (20 female) with a mean age of 75 +/- 1.2 years (range, 59 to 86 years) and a mean body surface area of 1.6 +/- 0.03 m2 (range, 1.3 to 1.7 m2). There were four deaths, one operative and three late noncardiac deaths. Follow-up of the 17 survivors for a mean of 20 +/- 3.1 months (range, 2 to 42 months) demonstrated symptomatic improvement in all 17 (all are now in New York Heart Association functional class I or II). There were no valve-related complications and no patient required long-term anticoagulation. Doppler echocardiographic studies were used to assess the in vivo hemodynamic profile of the valve. Mean postoperative aortic valve gradient was 34.1 +/- 2.7 mm Hg (range, 19 to 52 mm Hg). Functional valve orifice area was 1.1 +/- 0.09 cm2 (range, 0.6 to 1.8 cm2). Mean cardiac output was 3.92 +/- 0.17 L/min (range, 3.2 to 5.1 L/min) with a mean cardiac index of 2.5 +/- 0.11 L.min-1 x m-2 (range, 2.1 to 3.2 L.min-1 x m-2). In conclusion, we have demonstrated that aortic valve replacement with the 19-mm Carpentier-Edwards supraannular aortic valve has a low operative mortality and offers major clinical benefits despite moderate transprosthetic gradients. This approach provides an alternative management strategy in elderly patients who would otherwise require low-profile mechanical valves or aortic root enlargement. PMID- 1449308 TI - Optimal approach to the mitral valve: dissection of the interatrial groove. AB - Surgical exposure of the mitral valve has challenged surgeons for more than 30 years. Many ingenious, but often complex approaches have been devised during this time. Using the dissection of the interatrial groove to bring the left atrial incision more anterior and medial, we have achieved excellent exposure in more than 300 mitral valve procedures. This simple technique does not lengthen the procedure and is not associated with an increased risk of either early or late morbidity. PMID- 1449309 TI - Pulmonary "twinning" procedure: use of lungs from one donor for single-lung transplantation in two recipients. AB - Since the introduction of lung transplantation as an option for patients with end stage respiratory disease in the early 1980s, there have been substantial advances made in the technical aspects of transplantation as well as the early clinical results. With an ever-increasing number of patients being designated suitable candidates for transplantation, the volume of transplants in the foreseeable future will be limited more on the basis of donor lung supply than any other single factor. Pulmonary "twinning" provides an important step in ensuring that all suitable and available donor lungs are utilized whenever feasible. This report reviews the results of 20 single-lung transplantations carried out in five separate transplantation centers using organs retrieved from ten donors. The overall mortality rate in this group of patients was 5%, which compares very favorably with historical controls. No serious problem was noted with respect to increased perioperative morbidity or increased ischemic times in this group of patients. We suggest that this process should be considered and, wherever possible, adopted by all major lung transplant centers. PMID- 1449310 TI - Quantitation of particulate microemboli during cardiopulmonary bypass: experimental and clinical studies. AB - An electronic particle-size analyzer (Coulter Counter ZM) was used to quantitate particulate microemboli 15 to 80 microns in size during cardiopulmonary bypass. Through both laboratory studies and clinical research, we confirmed three main causes of microemboli: (1) infusion of banked blood stored for more than 3 days; (2) use of cardiotomy reservoirs; and (3) use of bubble oxygenators. The regression equation between number of particles and blood storage time was Y = 3.7262X + 10.244 (r = 0.886; p < 0.01). The number of microemboli from cardiotomy reservoirs was 2.8 to 5.1 times that from other sources (p < 0.01). The number of solid particles from bubble oxygenators was 1.8 to 3.2 times that from membrane oxygenators (p < 0.01). Electron microscopy showed that a large number of solid particles more than 20 microns in size were formed during heart-lung bypass. They obstructed the microcirculation and damaged pulmonary capillary endothelial and alveolar epithelial cells. The degree of histological damage was related to the number and size of microemboli and the duration of pulmonary microcirculatory obstruction. PMID- 1449311 TI - Complete cure after a seemingly unsuccessful operation for Wolff-Parkinson-White syndrome. AB - A 48-year-old man with Wolff-Parkinson-White syndrome and poorly tolerated atrial fibrillation underwent surgical dissection of an accessory pathway. After operation electrocardiogram revealed a very unfavorable outcome: sinus rhythm with persistence of delta waves alternated with sequences of complete atrioventricular block. Therefore, an early reoperation was planned. Fortunately, in the next days conduction through the accessory pathway and signs of atrioventricular block disappeared. Complete cure was observed during long-term follow-up. PMID- 1449312 TI - Pneumatocele complicating hyperimmunoglobulin E syndrome (Job's Syndrome). AB - The case of a boy with hyperimmunoglobulin E syndrome or Job's syndrome is presented to demonstrate the occurrence of pneumatoceles in this syndrome as well as their unusual natural history and failure to spontaneously resolve. Surgical resection was required for two complications in this patient, persistent bronchopleural fistula and a pulmonary abscess that destroyed one lung and required pneumonectomy. Pathologic examination of the specimens demonstrated the wall of the cysts consisted of granulation tissue with chronic active inflammation surrounded by infarcted pulmonary parenchyma with coagulative necrosis. The mechanism responsible for increased immunoglobulin E production in this syndrome is unknown, as is the manner in which elevated immunoglobulin E levels impair normal immune function. PMID- 1449313 TI - Surgical treatment of postinfarction ventricular septal defect with aortic stenosis. AB - A 69-year-old man with an acute postinfarction ventricular septal defect was also found to have aortic stenosis. Successful management required closure of the postinfarction ventricular septal defect and replacement of the stenotic aortic valve. The contribution of aortic stenosis to the cause of the infarction and the postinfarction ventricular septal defect, as well as the implications for surgical management, are discussed. PMID- 1449314 TI - Pleural liposarcoma presenting with respiratory distress and suspected diaphragmatic hernia. AB - A young woman with a history of diaphragmatic hernia presented to the hospital in respiratory distress and in premature labor. Her admission chest roentgenogram showed opacification of the left hemithorax, and her arterial blood gas analysis revealed hypoxemia. Emergency cesarean section and exploratory left thoracotomy were carried out; a large tumor occupied the left side of the chest, and pneumonectomy was performed. No diaphragmatic hernia was present. A pathologic diagnosis of primary liposarcoma was made. PMID- 1449315 TI - Retrograde coronary sinus cardioplegia in the presence of persistent left superior vena cava. AB - Administration of retrograde cardioplegia is hampered by the presence of a persistent left superior vena cava, which results in excessive runoff of solution into the persistent left superior vena cava and the right atrium. Technical modifications are described that permitted aortic valve replacement to be performed in a patient with persistent left superior vena cava using only retrograde cardioplegia. PMID- 1449316 TI - Post-atherectomy coronary artery aneurysm. AB - A 52-year-old man underwent an uneventful directional atherectomy of the left anterior descending coronary artery. Four months after the procedure unstable angina developed and on angiogram an aneurysm of the left anterior descending coronary artery was noted. The patient underwent bypass of the left anterior descending coronary artery. An attempt to exclude the aneurysm resulted in hemodynamic compromise and was discontinued. Follow-up angiogram 2 months after operation showed the aneurysm to be smaller. The patient is doing well 6 months after operation. PMID- 1449317 TI - Giant intrapericardial solitary fibrous tumor. AB - A 60-year-old man with a large pericardial effusion was found to have a giant intrapericardial solitary fibrous mesothelioma firmly attached to the ascending aorta and pulmonary trunk. Nine months after excision of the mass the patient is free from symptoms and signs of tumor recurrence. Solitary fibrous mesothelioma is a rare benign tumor and its excision is curative; however, because of the lack of information on its long-term behavior, close noninvasive follow-up of this patient is necessary. PMID- 1449318 TI - Management of severe bronchial ischemia after bilateral sequential lung transplantation. AB - A case of severe diffuse bronchial ischemia after bilateral sequential lung transplantation is presented. A combination of initial conservative treatment with silicone stenting and late bilateral retransplantation under stable conditions resulted in good clinical outcome. Factors in decision making and technical aspects of the stenting procedure are discussed. PMID- 1449319 TI - Permanent pacemaker implantation in premature infants less than 2,000 grams of body weight. AB - Pacemaker implantation in premature infants presents technical problems because of the relatively larger size of the pulse generator compared with their bodies. A new technique with which successful generator implantation was performed in 2 premature infants less than 2,000 g of body weight is described. The generator is wrapped in a Gore-Tex surgical membrane. A piece of membrane overlying the electrical contact surface of the generator is removed, and the generator is fixed to the abdominal wall in the peritoneal cavity. The technique is simple to perform and would give relative ease in generator exchange. PMID- 1449320 TI - Replacement of paracorporeal ventricular assist devices. AB - In this communication we describe a technique to change paracorporeal ventricular assist devices after the development of mechanical complications. This procedure is technically simple and in our experience does not require a sternotomy or cardiopulmonary bypass. Paracorporeal ventricular assist devices can be safely changed allowing continued support and survival. PMID- 1449321 TI - Inverted Y incision for accurate tailoring of patches and vessels. AB - When anastomosing vessels or using a patch to close a defect, it is often difficult to trim the vessel end or patch to size once the anastomosis is underway. We describe an inverted Y technique that is easy, is completely reproducible, and provides for an even, accurate fit. A continuous suture is run from the heel along either side to the widest part of the anastomosis. A straight incision is made from the tip of the patch or toe of the vessel to a point corresponding to the apex of the defect to be filled; from this point, approximately curved cuts are made to the edges of the patch or vessel just beyond the last sutures. The patch is now accurately shaped and the suture lines are completed. PMID- 1449322 TI - Repairing the degenerative anterior mitral leaflet. AB - This is a consecutive, nonselected series of 18 patients with degenerative mitral regurgitation requiring a reparative operation on the anterior mitral leaflet. A new technique of double-breasting the two leaflets when flail septal segments are encountered is introduced. PMID- 1449323 TI - The Nissen fundoplication. AB - The most commonly employed antireflux operation is the Nissen fundoplication. However, its origin and subsequent modifications are rarely defined. These aspects of the operation are reviewed in this article as are the results currently obtainable with the modern version of the operative procedure. PMID- 1449324 TI - Team approach for clinical cardiac surgery research. PMID- 1449325 TI - Length of the in situ right gastroepiploic artery for coronary artery bypass. PMID- 1449326 TI - Electrical instability during reperfusion. PMID- 1449327 TI - Pulmonary pseudotumor. PMID- 1449328 TI - Hemolysis after open heart operations. PMID- 1449329 TI - Penetrating cardiac trauma. PMID- 1449330 TI - Surgery of aortic dissections with GRF glue. PMID- 1449331 TI - Modified retractor to prevent peripheral nerve injury. PMID- 1449332 TI - [Value of an algorithm of automatic adaptation of the atrio-ventricular delay to the instantaneous atrial rate in cardiac stimulation]. AB - It has been suggested that an algorithm of automatic adaptation of the AV delay to the instantaneous atrial rate be introduced into the program of DDD pacemakers to reproduce the physiological adaptation of the PR interval to effort, characterised by progressive shortening inversely linearly related to the heart rate. In order to evaluate the potential benefits in conditions of "standard" programming (basal AV delay the same for all patients: maximal frequency of 1/1 AV synchronisation uniformly limited to 120 bpm), a haemodynamic study was undertaken in 10 patients who had permanent DDD pacemakers implanted for advanced AV block. Measurements were taken during two standardized exercise stress tests (20 W/2 mn steps from an initial load of 20 W) performed in a random order, one with a fixed AV delay of 156 ms and the other with an "automatic AV delay" allowing linear reduction from a maximum value of 156 ms at rest to a minimum value of 84 ms at the maximum heart rate of 120 bpm. At the peak of exercise the "automatic AV delay" significantly affected 4 parameters: the paced ventricular rate (p = 0.008) and rate-pressure product (p = 0.005) which increased, pulmonary capillary pressure (p = 0.03) and cycle-to-cycle variability of systolic and diastolic blood pressures (p = 0.02 < p < 0.0001) which decreased. There was a tendency (NS) to slowing of the spontaneous atrial rate and to increase in cardiac output. This increase was significant in some patients and seemed to be due to a good relationship between the individual optimal value of the value basal AV delay measured by Doppler echocardiography and the value programmed in this study (156 ms).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449333 TI - [Use of sternal zipper in open heart surgery]. AB - A sternal zipper was used in 50 patients with an unstable haemodynamic condition after open heart surgery. The patients were 19 women and 31 men (average age 51.6 years, range 7 to 67 years). The indications for surgery were aortocoronary bypass in 25 cases, replacement of the ascending aorta in 7 cases, valve replacement in 16 cases and correction of congenital heart disease in 2 cases. Twenty eight patients required circulatory assistance. The sternal zipper was used for 4 to 72 hours (average 29.5 hours) and mediastinal toilet was performed at least every 24 hours. At each opening of the zipper, 3 bacteriological swabs were taken from 3 different sites in the mediastinum and sent for culture. Global mortality was 36% (N = 18). The cause of death was a low output syndrome in 12 cases, hepatic and renal failure in 2 cases, resistant arrhythmia in 1 case, neurological complication in 1 case and septicaemia in 2 cases. There was one late death 3 months after hospital discharge which was attributed to a cardiac arrhythmia. The sternal zipper would seem to be a valuable option when the operative conditions are difficult, allowing the chest to remain open, so preventing cardiac compression during a critical period. PMID- 1449334 TI - [Ventricular repolarization]. AB - Ventricular repolarisation is the period that depolarised cells require to become polarised, that is to say excitable. In general cardiological practice, the duration of repolarisation is assessed by measuring the QT interval on the surface electrocardiogram. This measurement may be difficult because of the lack of precision in defining the end of the T wave. Automatic systems are becoming available and should circumvent these difficulties of manual measurements. Interpretation of a change in the QT interval during drug administration or related to cardiac pathology should take the many sources of physiological variation of ventricular repolarisation into account. One of the main causes of this variation is the heart rate which influences the duration of repolarisation in a complex manner. Analysis of the duration of repolarisation has many implications in pathology and pharmacology. Prolongation of the QT interval and its failure to adapt to the heart rate are trigger factors for torsades de pointe. Many drugs prolonging the duration of repolarisation and of the ventricular refractory period are being developed. Their effects are partially dependent on the heart rate. Finally, prolongation of the QT interval is associated with a poor prognosis after myocardial infarction. PMID- 1449335 TI - [Double-blind clinical and echocardiographic study of oral enoximone versus placebo in severe cardiac insufficiency]. AB - The effect of enoximone was assessed by a randomised double blind trial versus placebo. The clinical status of the patients was evaluated by the NYHA classification and quality of life score. Inotropic state was estimated from the maximum acceleration of aortic and pulmonary blood flow recorded by Doppler echocardiography. Thirty patients with severe cardiac failure, aged 66.4 +/- 14 years, symptomatic despite maximal therapy associating diuretics, digitalis, nitrate derivatives and angiotensin converting enzyme inhibitors, were included. Fifteen patients were given enoximone 100 mg three times a day orally (Group E) and the other 15 were given a placebo (Group P). The NYHA class and quality of life scores were assessed at D0, D4 and D31. Doppler echocardiography and Holter recordings were performed on D0 and D31. The two groups were comparable at D0. Ten patients abandoned the trial, 3 from Group E (including 1 death) and 7 from Group P (including 3 deaths). At D4, 13 patients from Group E and 8 from Group P were clinically improved (p < 0.05). At D31, the clinical state was stable or improved in 10 of the 12 patients in Group E and 6 of the 8 patients in Group P (NS). No secondary effects were severe enough to warrant the withdrawal of treatment: the frequency of ventricular extrasystoles was comparable in the two groups at D0 and D31. At D31 the maximal aortic acceleration had increased by 20% compared with D0 (p < 0.05) and the maximal pulmonary acceleration by 31% (p < 0.05) in Group E. The same parameters showed no significant change in Group P ( 6% and +5% respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449336 TI - [An unusual cause of sudden death: spontaneous dissection of coronary arteries. Apropos of 2 cases]. AB - The authors report two new cases of spontaneous dissection of the coronary arteries in women under 50 years of age without any predisposing factors and responsible for sudden death. One patient had dissection of the left anterior descending artery and the other had dissection of the left anterior descending and right coronary arteries. Special histological stains allow demonstration of abnormalities of the elastic tissue of the media in both cases. In the first case, a plaque of atheroma was present opposite the site of dissection but did not seem to be causal. In the second case, severe periadventitial cellular, infiltration of unknown origin was observed. This pathology of the young woman, often occurring in the postpartum period, is as rare as it is unpredictable. PMID- 1449337 TI - [Early postoperative thrombolysis of Saint-Jude aortic valve prosthesis]. AB - The authors report a case of thrombolytic therapy with streptokinase in the early postoperative period after aortic valve replacement with a Saint Jude medical prosthesis. After good initial progress, the patient had to be reoperated on the 12th postoperative day for sternal disunion. Reoperation was followed rapidly by progressive thrombosis of the aortic prosthesis demonstrated by repeated Doppler echocardiographic examination. The impossibility of eliminating mediastinitis led to medical thrombolysis. The outcome was favourable after a regressive cerebral embolic event. This case illustrates the value of Doppler echocardiographic examination in the postoperative period. Thrombolysis may constitute an alternative to reoperation when the operative risk is high. The risk of thrombolysis may not be as great as some believe. PMID- 1449338 TI - [Recurrent syncope during deglutition. An uncommon form of sinusal dysfunction]. AB - The authors report the case of a 69 year old man with a 16 year history of syncope occurring only while swallowing liquids. Two episodes were observed during a hospital admission to the intensive care unit for unstable angina and allowed documentation of prolonged sinus arrest (7 sec) causing syncope. In the light of this case and a review of the literature, the physiopathological role of deglutition in the genesis of cardiac conduction defects and arrhythmias is discussed and the new classification of sinus node dysfunction proposed by Bashour in 1985 is recalled. PMID- 1449339 TI - [Chronic dissecting aortic aneurysm and Turner's syndrome. Apropos of a case]. AB - Turner's syndrome is a genetic abnormality which is associated with cardiovascular anomaly in 20% of cases. Coarctation of the aorta and bicuspid aortic valve are the commonest malformations. Aortic dissection is the most serious complication affecting these patients. The authors report the case of chronic aortic dissection of the ascending and transverse aorta in a 27 year old patient with Turner's syndrome. The dissection was diagnosed on angiography. Transthoracic echocardiography showed aneurysmal dilatation of the aortic root. Surgical treatment consisted in replacement of ascending and transverse aorta with a Dacron tube. The anatomopathological analysis showed cystic medianecrosis of the aortic wall. The immediate postoperative evolution was satisfactory. The long-term outcome with a 4 year follow-up was excellent from the clinical and echocardiographic point of view. Turner's syndrome is probably associated with a congenital abnormality of the connective tissue especially of the elastic fibres of the aortic wall, explaining the development, though rare, of aneurysmal dilatation of the ascending and transverse aorta and dissection. These patients should be followed up regularly clinically and by transthoracic echocardiography. Other investigations such as transoesophageal echocardiography, magnetic resonance imaging and angiography are indicated when aortic dilatation, aortic regurgitation or chest pain suggesting aortic dissection are observed. PMID- 1449340 TI - [Spontaneous angina caused by spasm of the left coronary artery]. AB - A 42 year old woman presented with a one year history of retrosternal chest pain and back pain on effort and at rest sometimes accompanied by minor syncopal attacks. Transient atrioventricular block was documented during one such episode associated with hypotension. Coronary angiography showed spontaneous spasm of the left main coronary artery with clinical symptoms but no electrocardiographic changes. The spasm was relieved by injection of SIN-1. The similarity between the previous clinical symptoms and those observed at coronary angiography was in favour of the diagnosis of spasm of the left main coronary artery without atherosclerotic coronary disease. Treatment with calcium atherosclerotic coronary disease. Treatment with calcium blockers and platelet antiaggregants led to total regression of her symptoms with a follow-up of 5 months. PMID- 1449341 TI - [After oculo-stenotic reflex: oculo-nuclear reflex?]. PMID- 1449343 TI - [Immediate and long-term results of coronary surgery under age 40]. AB - The results of coronary artery surgery in young adults have not been extensively studied. We analysed the results of 221 patients under 40 years of age operated between 1979 and 1989 at the Pitie-Salpetriere Hospital. The patients were 200 men and 21 women with an average age of 36.2 years. The most common cardiovascular risk factors were smoking (69.6%) and hyperlipidaemia (52%). One hundred and eighteen patients (53.4%) had previous myocardial infarction (MI). Triple vessel disease was present in 129 cases, double vessel disease in 59 cases and single vessel disease in 33 cases. Twenty three patients had significant left main coronary disease. The number of bypass grafts per patient averaged 2.3. The operative mortality was 2.07% (6 cases), death being due to myocardial infarction in 4 cases. Perioperative myocardial infarction was diagnosed in 12 cases (5.05%). One hundred and ninety nine patients were followed up for an average of 7.4 years. Seven of the 17 late fatalities were of cardiac origin. The actuarial 9 year survival rate was 84%. Five patients were reoperated after an average of 6.4 years. Eighty five per cent of patients were asymptomatic at the last follow up examination. In conclusion, the symptoms of coronary artery disease in young adults can be effectively treated with a low operative risk by myocardial revascularisation surgery. Long-term follow-up remains essential to define the outcome in these patients. Systematic use of internal mammary artery bypass grafting should improve these results in the future. PMID- 1449342 TI - [Outcome of prognostic factors of infectious endocarditis over a 16 year period. Apropos of 471 cases]. AB - Four hundred and seventy one cases of infective endocarditis (IE) were reviewed: 338 native valve IE and 133 prosthetic valve IE (42 early and 91 late IE). Two periods were compared: 1973-1980 (250 cases) and 1981-1988 (221 cases). There was a decrease in native valve IE (78% to 64%) and an increase in late prosthetic valve IE (13% to 27%), little change with respect to age, causal cardiac disease, delay in diagnosis (except in native valve IE, 39 to 29 days), or frequency of complications, especially cardiac (50% and 51%). However, global mortality decreased from 41% to 27% (p < 0.001). The evolution of the frequency of cardiac complications, cardiac surgery and mortality for the two periods was: for native valve IE respectively 53% to 42%, 41% to 37%, 37% to 20% (p < 0.005); for early prosthetic valve IE respectively, 45% to 55%, 41% to 55%, and 82% to 50% (p < 0.05); for late prosthetic IE, respectively 34% to 69%, 34% to 69% and 37% to 36%. The frequency of surgery had therefore little influence on prognosis except in early prosthetic valve IE. The percentage of infections which could not be controlled medically decreased from 17% to 11%. The mortality of unoperated patients decreased from 46% to 28% (p < 0.01), suggesting more effective antibiotherapy, and the mortality of operated patients fell from 34% to 26%. Global surgical mortality was 35% in the acute phase (positive valve culture), 14% after sterilisation (p < 0.001) and the corresponding frequencies of paravalvular leaks was 17% and 4% (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449344 TI - [Heart valve surgery and associated diseases in aged subjects]. AB - The object of this study was to assess the additional risk related to associated pathology in patients aged 70 or over undergoing valvular heart surgery. Two hundred and thirty nine patients aged 70 to 87 years (average 74.6 +/- 3.2) underwent this form of surgery between October 1979 and June 1989. Sixty seven had coronary artery disease, 26 had atherosclerotic occlusive peripheral arterial disease, and 149 had one or more extracardiovascular pathology. Two hundred and thirteen patients underwent monovalvular and 26 bivalvular replacement. Coronary bypass was associated in 25 cases. Eighteen patients (7.5%) died in the 30 days following surgery. The perioperative mortality was not significantly greater in patients with extra-cardiac pathology (9.4% vs 4.4%; NS), in patients with coronary artery disease (11.9% vs 5.8%; NS), in patients with respiratory failure and FEV1 < 1 litre (1 death out of 20 cases) or in patients with renal failure and serum creatinine levels > or = 175 mumol/l (20% vs 6.3%, NS). Respiratory failure was the only extra-cardiac variable identified with increased perioperative morbidity. The perioperative mortality of elderly patients with valvular heart disease is greater than that of patients under 70 years of age (6.4% vs 2.1%) in our experience of the last 6 years p < 0.01). Associated arterial and extra-cardiac pathology does not significantly increase the mortality and strict selection of elderly inoperable patients together with improved surgical techniques and postoperative care has considerably reduced perioperative morbidity and mortality in this group of patients. PMID- 1449345 TI - [Patency of the artery responsible for myocardial infarction: role on ventricular function and long-term outcome]. AB - Out of 3,171 consecutive patients referred for coronary angiography, 240 were selected on the following criteria: recent primary myocardial infarction, single vessel coronary disease, no angioplasty or coronary surgery after the angiography which was performed 20 to 90 days after the onset of myocardial infarction. The patients were divided into 2 groups according to whether the artery responsible for infarction was patent (Group I: 115 patients) or not (Group II: 125 patients). The left ventricular ejection fraction was significantly higher in Group I (58 +/- 10.8%) than in Group II (53.7 +/- 11.3%) and end systolic and end diastolic left ventricular volumes were greater in Group II (51.8 +/- 22 ml/m2 and 88 +/- 22 ml/m2 respectively). Long-term follow-up (56 +/- 25 months in Group I and 61 +/- 26 months in Group II) was possible in 112 patients in Group I and 123 patients in Group II. Of the 7 patients who died in group II, 4 deaths were of cardiac origin; in addition, 2 cases of sustained ventricular tachycardia were observed in this group. None of the 6 deaths observed in Group I was of cardiac origin and there were no cases of ventricular tachycardia (p = 0.05). The functional status was identical in the two groups at the end of the study. These results suggest that the patency of the coronary artery responsible for myocardial infarction at a distance from the acute event is associated with better left ventricular function and a better long term prognosis. PMID- 1449346 TI - [Return to work of professional drivers after cardiac rehabilitation]. AB - This study analysed the possibilities of returning to work of professional drivers after a cardiac event and rehabilitation. The population comprised 94 consecutive patients, all men, average age 48.8 years (range 30 to 63 years) referred after coronary bypass surgery (N = 39), myocardial infarction (N = 38), angina (N = 4) or valve replacement surgery (N = 13). Advice on professional reinsertion was given after the rehabilitation program, authorization to drive being given in the absence of cardiac symptoms, residual myocardial ischaemia, severe left ventricular dysfunction and serious ventricular arrhythmias. After 35 months, 4 patients were lost to follow-up; of the 90 remaining patients, the frequency of return to work (maximal at the 9th month) was 65.6% with 84.7% obtaining a renewal of their driving licence. In this series, 81% of patients were asymptomatic, 2 died, 16.7% had further cardiovascular complications. The morbidity and mortality were significantly greater in the group who had to stop driving (N = 40) (32.5% vs 8%, p < 0.001). Non complications occurred during work in those who resumed driving. This study confirms the safety of allowing low risk professional drivers, identified during cardiac rehabilitation by simple, reliable clinical and paraclinical criteria, to return to work. PMID- 1449347 TI - [Abnormal origin of the left circumflex coronary artery: clinical, angiographic and prognostic aspects. Apropos of 30 cases]. AB - The object of this study of 30 patients with an anomalous origin of the left circumflex coronary artery was to define the clinical and angiographic features of this condition and to assess its influence on morbidity and survival. The 30 patients were 24 men and 6 women with ages ranging from 29 to 76 years. An anomalous origin of the left circumflex coronary artery should be suspected when two angiographic signs are present: firstly, the visualisation of a spur of opacification in the 30 degrees LAO view of left ventriculography, present in 93% or our patients; secondly, during selective left coronary angiography in the transverse view, an ascular zone is observed where the normal left circumflex artery should be. Confirmation of the diagnosis depends on opacification of the left circumflex arising from the right anterior sinus of Valsalva with a separate (37%) or common (23%) orifice with the right coronary artery or arising from a proximal segment of the right coronary artery/(40%). Five patients (17%) had a significant stenosis of the anomalous left circumflex coronary artery but this was always associated with lesions of the other coronary narrowing was observed. Of these patients, one had electrocardiographic signs of myocardial ischaemia and no other cause apart from the anomalous origin of the left circumflex to explain this ischaemia. The 30 patients were followed up for an average of 6.1 +/- 3.9 years. During this period, 1 cardiac death, 1 infarction, 5 cases of angina, 4 coronary bypass procedures, and 6 coronary angioplasties were observed. Nine patients (30%) had no cardiac event during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449348 TI - [Children and the environment]. PMID- 1449349 TI - [Modifying therapeutic in immune response]. PMID- 1449350 TI - [New data on the genesis of sleep-wakefulness rhythm in children aged 4-15 months]. AB - The present study deals with the ontogeny of the sleep-wakefulness rhythm in 12 children from the 4th to the 15 month of age. The main findings were as follows: 1. The circadian rhythm of wakefulness and sleep is clearly sep up as of 4 months of age and is characterized by 3 main parameters: a long uninterrupted night sleep period which includes the time interval from midnight to 4 a.m. The duration of this period of time is always equal to or higher than 400 min. The periodicity of the last falling asleep before midnight and the periodicity of the first awakening after midnight are equal or very close to 24 hours. Both seem to be mutually adjusted or connected to each other. 2. Some ages are characterized by significant changes in the daily distribution of the number and duration of sleep spans. 3. These changes suggest the existence of several ultradian rhythmicities which prevail successively throughout the development period under study. 4. There are many important differences between girls and boys. PMID- 1449351 TI - [Treatment of insulin-dependent diabetes mellitus by insulin pump in children under 7 years of age]. AB - BACKGROUND: Conventional insulin therapy for diabetes mellitus is sometimes inadequate for controlling metabolic disturbances in young children; the risk of hypoglycemia is particularly high at this age. METHODS: Ten newly-diagnosed insulin-dependent diabetic children aged 1 to 7 years were treated by continuous subcutaneous insulin infusion using a portable pump. The mean duration of treatment was 17 months (4 to 42 months). RESULTS: The mean individual capillary blood glucose calculated over periods of 6 months ranged from 84 +/- 23 to 206 +/ 97 mg/dl. The glycosylated hemoglobin values were 6.5 to 8.9% during the same period. There was no hypoglycemic coma; 7 children experienced a total of 16 episodes of ketonuria. The average daily dose of insulin used by these 10 patients was 0.72 +/- 0.24 units/kg. CONCLUSION: Continuous subcutaneous insulin infusion is a feasible therapy and it was well tolerated even in the youngest children. External insulin infusion devices appear to be an alternative to conventional insulin therapy and a way of overcoming the therapeutic difficulties encountered with these young patients. PMID- 1449352 TI - [Congenital deglutition disorder revealing cerebral stem disorders. 12 cases with neurophysiological study]. AB - BACKGROUND: Respiratory problems in neonates and infants may be the result of a variety of neuromuscular dysfunctions. Neurologic evaluation of functions, such as sucking and swallowing, may be difficult in these very young infants and can be helped by neurophysiological studies. METHODS: 12 infants admitted because of repeated episodes of respiratory obstruction due to difficulties of sucking and/or swallowing took part in the study. The neurophysiological studies included electromyography of the facial, lingual and pharyngeal muscles, brain stem auditory evoked potentials and measurement of the blink reflexes. The results were correlated with events during the perinatal period and those that occurred during the follow-up. RESULTS: Dysphagia was evident from the neonatal period; it was complicated by nasal reflux and aspiration bronchopneumopathy. Facial diplegia was observed in 8 patients. 9 patients failed to thrive. The electromyographic patterns showed partial denervation of the facial, lingual and pharyngeal muscles in all cases; the blink reflex was altered in 11 cases, and the brain stem evoked potentials were abnormal in 3 of the 8 cases tested. 7 of the infants had histories of pregnancy and obstetrical abnormalities, and/or fetal distress. The swallowing function partially improved within several months. CONCLUSIONS: Neurophysiological studies indicate neurofunctional alterations in the VII, IX, X and XII cranial nerve nuclei, V and VII pathways and the auditory tract. These lesions and the time course of improvement suggest that they are due to pre- or perinatal anoxo-ischemic brain stem injury. PMID- 1449353 TI - [Dysregulation of plasma 1,25(OH)2D in calcium restriction in hypercalciuric children]. AB - BACKGROUND: The effect of calcium restriction on the plasma concentration of 1,25(OH)2D in normo- and hypercalciuric children remains unknown. METHODS: We studied phosphate and calcium metabolism of 8 normocalciuric and 8 hypercalciuric children aged 4 to 16 years, under 3 conditions: on a normal dietary calcium intake after a 5-day calcium-restricted diet, and after oral calcium loading. The healthy, normocalciuric children had histories that included no renal failure of abnormalities of phosphate and calcium metabolism. Four of the 8 hypercalciuric children had urolithiasis, 1 had hematuria and the 3 others had idiopathic hypercalciuria. Blood samples were analyzed for calcium, creatinine, immunoreactive parathyroid hormone, cAMP, 25(OH)D and 1,25(OH)2D concentrations. Urine samples were analyzed for calcium, phosphorus, creatinine and cAMP. RESULTS: On the normal dietary calcium intake, the hypercalciuric children had higher urinary calcium excretion and plasma 1,25(OH)2D levels and lower TmP that did the controls. The 1,25(OH)2D levels of the normocalciuric children were significantly increased after 5 days of dietary calcium deprivation, but those of the hypercalciuric children were not. The other parameters (essentially PTH, cAMP and TmP) varied similarly in the two groups. CONCLUSION: The results suggest that: a) calcium restriction influences 1,25(OH)2D levels in normocalciuric subjects via a PTH- and phosphor-independent mechanism; b) dietary control of renal vitamin D metabolism is impaired in hypercalciuric patients. PMID- 1449354 TI - [Familial infantile cortical hyperostosis (Caffey's disease) with osteolytic lesions of the skull]. AB - BACKGROUND: The parietal and frontal bones are rarely affected in infantile cortical hyperostosis. CASE REPORTS: Case n. 1: A 14-day-old boy developed a swelling of the left eyelid that extended to the face in a few days. It was tender and associated with fever. Laboratory findings were increased (RBC sedimentation rate and other signs of inflammation). CT scan of the sinuses, soft tissues and bones was normal, but at the age of 23 days minimal patches of rarefaction were seen on X-rays of the frontal bones. These lacunar areas gradually extended, with the inflammation persisted. A new CT scan at 6 months of age confirmed the existence of lacunar areas in the skull, but failed to find any lesions of the mandibles or nasal bones. At that time, scintigraphy showed inflammatory lesions of the skull and ribs. All clinical, laboratory and radiological findings spontaneously disappeared within 3 years. Case n. 2: Similar swellings of the face developed at the age of 15 days in the brother of case n. 1. The laboratory findings were identical to those for his brother, and there were minimal lytic areas of the vault of skull without any other lesions. At 3 months of age, X-rays confirmed the existence of skull lesions and showed cortical hyperostosis of the left humerus. Similar cortical hyperostosis of nasal bones appeared at the age of 8 months, while the inflammatory syndrome persisted. All findings gradually and spontaneously disappeared within 18 months. CONCLUSIONS: Cortical hyperostosis are usually most prominent in the lower extremities in cases of familial infantile cortical hyperostosis. The lesions were largely confined to the skull in our cases, with no lesions of the mandible. The disease was only identified in the first case after a protracted course with unpredictable remissions and relapses and the discovery of the cortical hyperostosis in his brother. PMID- 1449355 TI - [Cerebral lesions observed in a twin after the in utero death of the other twin. Fetal anoxia-ischemia can be the possible mechanism (3 cases)]. AB - BACKGROUND: The death of one twin in utero may result in visceral lesions, of possible vascular origin, in the surviving twin when the pregnancy is monochorionic and diamniotic. CASES REPORT: Case n. 1: The death of one twin and enlargement of the ventricular system in the other were seen by ultrasonography at 24 weeks of pregnancy, 8 weeks after the mother had a fall on the stairs. The heterogeneous imaging in the inferior part of placenta suggested a clot in this area. The pregnancy was terminated at 28 weeks because the ventricular dilatation continued to increase. The newborn died a few minutes later and examination of the placenta showed that the pregnancy was monochorionic and monoamniotic. Case n. 2: The death of one twin with macerating features was seen by ultrasonography at 31 weeks. The other twin was born at 32 weeks of a dichorionic, diamniotic pregnancy. Injection of milk into the placental vasculature failed to visualize any vascular anastomoses between the two placentas, but ultrasonography showed bilateral cystic lesions in the frontal lobes of the brain. Case n. 3: Acute polyhydramnios developed at 21 weeks of pregnancy; it was treated by 3 amniocenteses, while ultrasonography of the twins was normal. A fetal transfusion syndrome was observed at birth, the pregnancy being monochorionic and diamniotic. Cranial ultrasound on day 6 was normal in the recipient twin, but showed numerous cerebral cavities in the donor, which was confirmed at autopsy after that this twin suddenly died at 2 months of age. CONCLUSIONS: Brain lesions of vascular origin, can be observed in any type of twin pregnancies. They may be the result of transfusion of clot or thromboplastin-rich blood from the donor fetus through vascular anastomoses in a monochorionic placenta. They also may be due to anoxo ischemic lesions in the absence of such anastomoses, or, in the fetal transfusion syndrome, to circulatory difficulties in one of the twins, as observed in premature singletons. In the cas of anoxo-ischemic lesions, anticipating the birth of the surviving twin is not justified. PMID- 1449357 TI - [Trace elements and low birth weight newborn infants]. PMID- 1449356 TI - [A cause of neonatal respiratory distress: cerebral tissue heterotopia in the cavum]. AB - BACKGROUND: Brain heterotopia can be reflected in disturbances of the oropharynx during the neonatal period, such as acute upper airway obstruction. The main differential diagnosis is encephalocele, which must be recognized before undertaking any surgical procedure. CASE REPORT: A boy, aged 5 days, with a cleft palate and bifid uvula, was admitted for respiratory distress. The distress initially occurred during bottle-feeding, but later became permanent. A solid mass, seemingly implanted in the superior wall of the pharynx, was successfully removed by forceps. A later CT scan showed the absence of any defect in the cribriform plate, thus excluding diagnosis of encephalocele. Histological, examination of the mass showed glial tissue without neurons. CONCLUSION: The presence of a pharyngeal mass in a newborn signals three possibilities: teratoma, heterotopic brain tissue or encephalocele. Encephalocele must by ruled out by a preoperative CT scan with a water soluble contrast agent in order to avoid CSF leakage and meningitis. Respiratory distress should be treated by oral endotracheal intubation to allow time for CT scan investigation. PMID- 1449358 TI - [Value of intravenous immunoglobulins for the prophylaxis and treatment of neonatal infections]. PMID- 1449359 TI - [Conservative treatment of renal insufficiency in the first year of life]. PMID- 1449360 TI - [Antibiotherapy as first choice in neonatal septicemia]. PMID- 1449361 TI - [False positive serologic tests for Lyme disease in echovirus meningitis]. PMID- 1449362 TI - [Thyroid goiter revealing Burkitt's lymphoma]. PMID- 1449363 TI - [Exogenous surfactants. The pulmonary surfactant. Relations between structure and function]. PMID- 1449364 TI - [Exogenous surfactants of natural origin. What is new in 1992?]. PMID- 1449365 TI - [Artificial exogenous surfactants]. PMID- 1449366 TI - [Exogenous surfactants. Indications and limits in 1992]. PMID- 1449367 TI - [Autoimmune diseases in pediatric. Complement deficiencies and anticardiolipin syndromes. Genetic complement deficiencies and autoimmune diseases]. PMID- 1449368 TI - [Cold urticaria, cutaneous vasculitis and C4B homozygote deficiency. Apropos of 2 cases with a familial study]. PMID- 1449369 TI - [Thrombosis and antiphospholipid antibodies in systemic lupus erythematosus with pediatric onset]. PMID- 1449370 TI - [False forms of cardiolipin syndrome. Apropos of a case]. PMID- 1449371 TI - [Thrombotic manifestations and acute distal ischemia in primary antiphospholipid syndrome in children]. PMID- 1449372 TI - [Energy intake and appetite regulation in infants]. PMID- 1449373 TI - [Maternal breast feeding and growth factors]. PMID- 1449374 TI - [Can allergy be prevented by the right nutrition during infancy?]. PMID- 1449375 TI - [Early diversification of nutrition of the infant. Advantages and disadvantages]. PMID- 1449376 TI - [General clinical aspects of growth during puberty]. PMID- 1449377 TI - [Value of predictive methods of height in adulthood]. PMID- 1449378 TI - [Hormonal regulation of growth during puberty]. PMID- 1449379 TI - [Simple delayed puberty in boys]. PMID- 1449380 TI - [Growth and puberty in Turner syndrome]. PMID- 1449381 TI - [Growth and precocious puberty. Results of treatment by LHRH analogs]. PMID- 1449382 TI - Brain morphology and schizophrenia. A magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures. AB - We used magnetic resonance imaging to examine the morphologic characteristics of the amygdala/hippocampus, prefrontal cortex, and caudate nucleus in 29 healthy volunteers matched for age, gender, and head of household socioeconomic status and 44 patients with chronic schizophrenia. Total volumes of these structures were determined from 3-mm contiguous coronal sections. Schizophrenic patients, compared with healthy controls, had significantly smaller right and left amygdala/hippocampal complex volumes, smaller right and left prefrontal volumes, and larger left caudate volumes. A secondary analysis revealed reductions in the right and left amygdala and the left hippocampus. In addition, prefrontal white matter, but not gray matter, was reduced in the schizophrenic patients. Moreover, the right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume (r = .39), data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia. We studied the implications of these data for the pathophysiology of schizophrenia. PMID- 1449383 TI - Striatal metabolic rate and clinical response to neuroleptics in schizophrenia. AB - A low metabolic rate in the caudate nucleus and putamen in schizophrenic patients while they were not receiving medication was found to predict a favorable clinical response to haloperidol. Twenty-five patients (21 men and four women) entered a double-blind crossover trial of haloperidol and placebo; to our knowledge, this is the first such trial with positron emission tomography to be reported. Patients received either placebo or medication for the first 5 weeks, and they received the other treatment for the second 5 weeks. Positron emission tomographic scans were obtained at weeks 5 and 10. Patients with low relative metabolic rates in the caudate nucleus and putamen while they were receiving placebo were more likely to show decreases in their Brief Psychiatric Rating Scale scores with haloperidol treatment than individuals with normal or high metabolic rates. Among responders, haloperidol treatment had a "normalizing" effect on metabolic activity in the striatum, with the metabolic rate while they were receiving haloperidol being higher than that while they were receiving placebo. Nonresponders were more likely to show a worsening of hypofrontality while they were receiving medication and an absence of change in the striatum. PMID- 1449384 TI - Schizophrenics show spatial working memory deficits. AB - The present study demonstrates that schizophrenics are impaired on spatial delayed-response tasks, analogous to those that have been used to assess the working memory function of the dorsolateral prefrontal cortex in rhesus monkeys. Schizophrenic patients and two control groups, normal subjects and bipolar psychiatric patients, were tested on the oculomotor version of the memory task, a haptic version of the same task, and two control tasks: a sensory task that did not require working memory and a digit span test. The schizophrenic patients showed marked deficits relative to the two control groups in both the oculomotor and haptic delayed-response tasks. They were not, however, impaired on the digit span test, which taps verbal working memory as well as voluntary attention, and on the sensory control task, in which their responses were guided by external cues rather than by spatial working memory. These findings provide direct evidence that schizophrenics suffer a loss in representational processing and that this deficit is modality independent. These data on spatial working memory add to the growing evidence for involvement of the dorsolateral prefrontal cortex in schizophrenic disease. PMID- 1449385 TI - Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944-1945. AB - We tested the hypothesis that first-trimester exposure to acute food deprivation is a risk factor for schizophrenia. A sharp and time-limited decline in the food intake of the Dutch population following a Nazi blockade in 1944 to 1945 created a unique if tragic natural experiment to test this hypothesis in three regions of Holland (west, north, and south). In the west, or famine region, birth cohorts exposed to severe food deprivation (an average daily ration under 4200 kJ) during the first trimester showed a substantial increase in hospitalized schizophrenia for women but not for men. Relative risks for women were 2.17 for "broad" and 2.56 for "restricted" schizophrenia. Moderate food deprivation during the first trimester (average daily ration under 6300 kJ) was not associated with increased risk of schizophrenia in the famine region. In the north and south regions, numbers were smaller and there was no exposure to severe famine. Birth cohorts exposed to moderate food deprivation during the first trimester showed a trend toward increased risk of schizophrenia for women. These findings give plausibility to the proposition that early prenatal nutrition can have a gender specific effect on the risk of schizophrenia. PMID- 1449386 TI - Ventricular enlargement in schizophrenia: is there really a gender effect? PMID- 1449387 TI - Characterizing organic delusional syndrome. PMID- 1449388 TI - Neuroleptic treatment, symptoms of schizophrenia, and plasma homovanillic acid concentrations revisited. PMID- 1449389 TI - [Mucous membrane of the gastric antrum in late periods after selective proximal vagotomy with surgical drainage of the stomach and duodenum]. AB - A clinicomorphological analysis was performed of the gastric antrum mucous membrane of 60 patients after selective proximal vagotomy because of stenosing duodenal ulcer. The patients were subdivided into two randomized groups depending on the type of the draining operation. The first group had a gastroduodenoanastomosis for the gastric drainage and the second group underwent duodenum plasty (drainage of the duodenum). Discontinuation of the pylorus function in the gastric drainage operation resulted in higher incidence and intensity of duodenum-gastric reflux and made more severe antrum gastritis; reflux-gastritis developed frequently. Morphological signs of reflux-gastritis in 95% of cases coincided with the results of the radionuclide method. Duodeno gastric reflux decreased as a rule Helicobacter pylori (HP) contamination of the mucous membrane but did not eliminate it completely in all cases. The combination of these two factors resulted in more severe gastritis than that provoked by each of them separately. The etiology of gastritis and its intensity may be determined only by morphological examination of gastric mucous membrane. The results of endoscopic and histologic methods coincided in 70% of cases. Duodenal-gastric reflux, HP and high acid production play a certain role in ulcer recurrence. PMID- 1449390 TI - [Gastric ulcers in liver cirrhosis and their exposure to low-intensity infrared laser radiation]. AB - By means of light, scanning electron microscopy and planimetry, the pathomorphology of gastric ulcers (GU) was investigated in patients who had died from liver cirrhosis (LC) and in rats with experimental portal hypertension (PH). It was noticed that GU are frequent (13.3%) in patients with LC. Experimental GU induced in rats with PH persist longer and their areas are larger than in ulcers without cirrhosis. The treatment of ulcers through abdominal wall with low intensive infrared laser irradiation (LILR) causes significant acceleration of their epithelialization in the rat without cirrhosis. Ulcers in the animals with cirrhosis do not repair under LILR influence, but their area significantly decreases after forming collateral shunting. The congestion in the portal system is the main pathogenetic element in gastroesophageal ulcerogenesis. The laser therapy without decreasing portal hypertension is not efficient. PMID- 1449391 TI - [Interaction of indigenous parietal microorganisms with cells of the digestive tract mucosa]. AB - By means of light, electron microscopy and stereomorphometry the interaction of microorganisms (MO) and cells of the mouth, stomach and gut mucous membrane was studied in different pathologic conditions on clinic and experimental material. No penetration was noted of MO into cells of the keratinized squamous epithelium, they were present in intercellular spaces. In the stomach, MO as a rule interact with mucocytes altering their surface. Spirillum-like MO sometimes penetrate into the parietal cells. In the small bowel MO may penetrate the cells causing lysis of apical membranes and photocytosis changing the microvilli structure. MO may enter the goblet cells during the secretion. They may settle in the cell cytoplasm without causing its alteration. In crypts, near Paneth cells, MO were subjected to lysis. The peculiarities of MO interaction with cells depend on their structural-functional status. PMID- 1449392 TI - [Zinc content of pancreatic islets in diabetes]. AB - Content and distribution of zinc was studied in the pancreatic islets in human and rabbit diabetes. The diabetes development is followed by a decrease of zinc content in the insulin-producing cells in parallel with the severity of diabetes. The damage to the islet B-cells is the cause of zinc metabolism disturbance in the endocrine pancreas. Influence of high glucose concentration in the blood may be another factor. PMID- 1449393 TI - [Immunohistochemical detection of insulin and insulin-like growth factors using antibodies to various parts of the insulin receptor molecule]. AB - The indirect peroxidase-labeled antibody method was used to localize insulin receptors (IR) in the liver and brain of rats under various physiological conditions. Light- and electron-microscopically, specific immunohistochemical reaction was revealed in hepatocytes and endothelial cells of brain vessels with antisera against alpha- and beta-subunits of IR. Immunohistochemical reaction in the hypothalamic median eminence was observed only with antiserum to peptides with amino acid sequence corresponding to sequence 48-77 of human placenta IR. Electron-microscopically, immunohistochemical reaction was revealed on the cytoplasmic membranes and granular endoplasmic reticulum of the fibroblasts in the pericapillary space. The receptors observed correspond to receptors to insulin-like growth factor-1. PMID- 1449395 TI - [Criticism of current medical ideology]. PMID- 1449394 TI - [A case of Holt-Oram syndrome]. AB - Description of a rare hereditary heart disease in a newborn (heart-hand symptom complex: changes of the shape and structure of a forearm with the absence of thumb and finger V plus atrial septal defect) is presented. The combined effect of genetic and environmental influences is regarded as a cause of the syndrome. PMID- 1449396 TI - [Recombination transformations as one of the mechanisms of qualitative changes in living systems]. AB - New quality in the nature, according to the author, may appear not only in the process of quantitative changes, but by means of various recombinations (regrouping) of elements composing the system without changing their number. The variants of such regrouping are discussed. Recombinant (conformative) changes which are widely spread in the nature, play an important role in the host adaptive reactions. PMID- 1449397 TI - The neuropsychology of the cerebellum: an emerging concept. PMID- 1449398 TI - The brain stem viewed in situ from above. PMID- 1449399 TI - Selegiline and manic behavior in Parkinson's disease. PMID- 1449400 TI - Open controlled therapeutic trial of intravenous immune globulin in relapsing remitting multiple sclerosis. AB - Ten patients with relapsing-remitting multiple sclerosis were treated with intravenous immune globulin, 0.4 g/kg per day for 5 consecutive days, and then with additional booster doses of immune globulin of 0.4 g/kg, once every 2 months, for the next 12 months. Ten untreated patients with relapsing-remitting multiple sclerosis who were matched with the study patients for age, disease duration, and number of attacks per year served as controls. Immune globulin treatment was well tolerated, with no side effects. The exacerbation rate decreased from 3.7 +/- 1.2 exacerbations per year before treatment to 1.0 +/- 0.7 exacerbations per year during the treatment in the immune globulin-treated patients, while it remained unaltered in the controls. The posttreatment Kurtzke Expanded Disability Status Scale score decreased from a mean of 4.45 to 4.15, whereas in controls it increased from 3.55 to 3.75. The results suggest that immune globulin suppresses the ongoing pathologic process in multiple sclerosis and may be a promising treatment to prevent disease exacerbations. PMID- 1449401 TI - Quality of life in multiple sclerosis. Comparison with inflammatory bowel disease and rheumatoid arthritis. AB - Multiple sclerosis (MS) and other chronic illnesses can drastically decrease quality of life (QOL), but there has been little systematic study of QOL in patients with chronic medical diseases. We analyzed QOL in 68 patients with MS, 164 patients with inflammatory bowel disease, and 75 patients with rheumatoid arthritis. The previously validated test instrument was a standardized interview consisting of 41 questions clustered in four subscales: functional and economic scale, social and recreational scale, affect and life in general scale, and medical problems scale. Patients were included in the study if they had a definite medical diagnosis and disease duration of 10 years or longer. In the patients with MS, Kurtzke's Expanded Disability Status Scale correlated strongly only with the medical problems score. Of Kurtzke's Functional System Scales, only the visual Functional System Scores was correlated with total QOL and subscale scores, suggesting that vision is strongly related to QOL. Duration of MS was unrelated to QOL scores. There were significant differences between patients with MS, inflammatory bowel disease, and rheumatoid arthritis on the subscale and total QOL scores. Results suggested that QOL was best in the inflammatory bowel disease group and worst in the MS group. Numerous statistically significant differences on individual questions were evident, suggesting that unique clinical profiles differentially characterize these diseases. Assessments of QOL are a meaningful addition to impairment scales, such as Kurtzke's Expanded Disability Status Scale. Furthermore, QOL scores may meaningfully measure the impact of a chronic medical disease, such as MS, compare the impacts of different diseases, and assess the effects of therapeutic intervention. PMID- 1449402 TI - Effects of cigarette smoking on motor functions in patients with multiple sclerosis. AB - The acute effects of cigarette smoking on motor functions were examined in 21 patients with multiple sclerosis and 11 healthy control subjects. The motor function in the upper extremities was assessed by a simple test battery. Sixteen of 21 patients had a transient deterioration of their motor function immediately after smoking, lasting for 10 minutes. The mean decrease in motor performance score for all 21 patients was 14%. With the same tests performed without smoking only three of 14 patients had a deterioration and the group had a mean 8% improvement. The control group showed a steady improvement over time, both in smoking and in simulation experiments. We conclude that nicotine causes a transient worsening of motor functions in patients with multiple sclerosis, which can be due to its effects on the central nervous system or vegetative-vascular functions. PMID- 1449403 TI - Neuropsychological importance of subcortical white matter hyperintensity. AB - Subcortical hyperintensity on magnetic resonance imaging is a common incidental finding in healthy elderly subjects. The relationship of such changes to cognitive functioning remains unclear, however, because only a small number of studies have examined this issue with conflicting results. We therefore assessed 66 healthy adult volunteers (mean [+/- SD] age, 61.8 +/- 15.8 years) with magnetic resonance imaging scans rated for subcortical hyperintensity, and with two neuropsychological instruments selected a priori on the basis of previous reports in the literature. Findings were highly significant for both the Benton Facial Recognition Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol. However, in both cases, the majority of variance was accounted for by age and educational level. Effects of subcortical hyperintensity were not significant. We conclude that subcortical hyperintensity in healthy adults does not relate to cognitive functioning, at least with these two instruments. PMID- 1449404 TI - Comparisons of verbal fluency tasks in the detection of dementia of the Alzheimer type. AB - The performances of 89 patients with dementia of the Alzheimer type (DAT) and 53 demographically matched elderly normal control subjects were compared on four verbal fluency measures (category, letter, first names, and supermarket fluency). Receiver operating characteristic curves were plotted to determine each fluency tasks' sensitivity (ie, true-positive rate) and specificity (ie, true-negative rate). Category fluency demonstrated the greatest degree of discrimination between patients with DAT and normal control subjects (sensitivity, 100%; specificity, 92.5%); letter fluency was the least accurate (sensitivity, 89%; specificity, 85%). Separation of patients with DAT by gender revealed similar findings. In further analyses with a subgroup of 21 mildly impaired patients with DAT, category fluency lost none of its discriminative capabilities, whereas all other fluency measures showed marked reductions in discriminability. We conclude that this superiority of category fluency is due to its dependence on the structure of semantic knowledge, which deteriorates in the early stages of DAT. PMID- 1449405 TI - Validation of the 3-oz water swallow test for aspiration following stroke. AB - A 3-oz water swallow test identified 80% (16/20) of patients aspirating during a subsequent videofluoroscopic modified barium swallow examination (sensitivity, 76%; specificity, 59%). It also identified patients with more severe dysphagia aspirating larger amounts (sensitivity, 94%; specificity, 26%) or thicker consistencies (sensitivity, 94%; specificity, 30%) of test material. The 3-oz water swallow test is a sensitive screening tool for identifying patients at risk for clinically significant aspiration who need referral for more definitive modified barium swallow evaluation. PMID- 1449406 TI - Cerebral glucose metabolism in Parkinson's disease with and without dementia. AB - Although cognitive impairment is commonly associated with Parkinson's disease, the relative importance of cortical and subcortical pathologic changes to the development of dementia is controversial. Characteristic abnormalities in cortical glucose metabolism have been reported previously in Alzheimer's disease, a disease in which cortical changes predominate. We measured cerebral glucose metabolism with positron emission tomography in 20 control subjects and in 14 patients with PD with mental status ranging from normal to severely demented to determine whether changes in cortical glucose metabolism occur in early PD and whether the degree and pattern of metabolic change relate to the severity of dementia. The patients were divided into demented and nondemented groups according to the results of neuropsychological assessment. Age-adjusted covariance analyses were performed, since the age distribution varied between groups. The nondemented patients with PD showed widespread cortical glucose hypometabolism without any selective temporoparietal defects. The pattern of glucose hypometabolism seen in the demented patients with PD resembled that described in patients with Alzheimer's disease; ie, there was a global decrease in glucose metabolism, with more severe abnormalities observed in the temporoparietal regions. PMID- 1449407 TI - Elevated neopterin levels in Guillain-Barre syndrome. Further evidence of immune activation. AB - Neopterin is a by-product of guanosine triphosphate metabolism and is produced by macrophages in response to lymphocytic activation. We have studied serum neopterin levels in patients with Guillain-Barre syndrome to obtain further evidence of immune activation in this disease. Serum neopterin levels were significantly elevated in patients with Guillain-Barre syndrome compared with patients with other peripheral neuropathies and multiple sclerosis and with healthy control subjects. Serial analysis demonstrated that as neopterin levels fell, the clinical status of the patients with Guillain-Barre syndrome improved and soluble interleukin 2 receptor levels dropped. Thus, lymphocytic and macrophage activation may play a role in the pathogenesis of Guillain-Barre syndrome. PMID- 1449408 TI - Frontal lobe dysfunction in unilateral lenticulostriate infarcts. Prominent role of cortical lesions. AB - Most studies on frontal lobe dysfunction (FLD) in patients with striatal lesions did not consider possible associated cortical lesions not seen on computed tomographic scans. To determine the possible role of such cortical lesions, we assessed FLD in 10 patients with unilateral lenticulostriate infarct on computed tomographic scans. Magnetic resonance imaging revealed an associated cortical infarct not seen on computed tomographic scans in four patients. Using a battery of neuropsychological tests sensitive to FLD, we found that (1) the crossed tapping test was the only FLD test significantly disturbed in patients with pure unilateral lenticulostriate infarcts, (2) FLD was only present in patients with associated cortical infarct, and (3) caudate lesions only account for the number of echopraxic errors in the crossed tapping test. We conclude that unilateral isolated lenticulostriate infarcts might not lead to FLD, even though they may disturb the development of strategies involved in motor procedural learning. PMID- 1449409 TI - Suicide and patients with neurologic diseases. Methodologic problems. AB - OBJECTIVE: The suicide risk in patients with many neurologic diseases has been reported to be greater than that in the general population. Studies on the subject are, however, often encumbered with methodologic problems. We appraised these problems and, based on an evaluation, reappraised knowledge of the suicide risk in patients with specific neurologic diseases. DATA SOURCE: Using the computerized database MEDLINE, we identified all published reports with the key words suicide, attempted suicide, and neurologic diseases. STUDY SELECTION: We assessed and reviewed studies concerning the most common neurologic diseases for methodologic problems in the study design. DATA EXTRACTION: The following methodologic problems emerged during our review: (1) choice of study type, ie, autopsy study or follow-up study; (2) choice of study population; (3) choice of control groups; (4) epidemiologic/statistical methods used; and (5) validity of statistics reported. DATA SYNTHESIS: We analyzed the methodologic problems in studies of patients with multiple sclerosis, epilepsy, Huntington's chorea, spinal cord lesions, cranial trauma, brain tumors, Parkinson's disease, vascular disorders, and migraine. In most of the studies, the methods used gave rise to uncertainty about the conclusion presented. CONCLUSION: An increased suicide risk was found in patients suffering from multiple sclerosis and spinal cord lesions as well as in selected groups of patients with epilepsy. In other neurologic diseases, the suicide risk may be increased, but the results are uncertain due to the methodologic problems in the study design. PMID- 1449410 TI - Effect of ethanol on mouse brain microsomal phospholipid turnover. AB - In an investigation of the effects of chronic and acute ethanol administration on phospholipid synthesis, mice subjected to chronic or acute ethanol administration were intraventricularly injected with 1,332 kBq of 2-3H-glycerol (3H-glycerol) and 4,070 kBq of 32P-phosphoric acid 15 min after the ethanol injection. One hour later, mice were sacrificed, and brain microsomes were prepared for analysis of incorporation of radioactivity into phospholipids. Chronic ethanol treatment significantly decreased incorporation of 3H-glycerol and 32P-phosphoric acid into phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol plus phosphatidylserine. However, acute ethanol treatment had no marked effect on incorporation of 3H-glycerol or 32P-phosphoric acid into any of these phospholipids. On the other hand, chronic ethanol administration had no significant effect on incorporation of the radioisotopes into triphosphoinositide (TPI) or diphosphoinositide (DPI) in microsomal fractions, or the 3H- and 32P TPI/DPI ratios. However, acute ethanol administration decreased the incorporation of 3H-glycerol into DPI and TPI, but did not change the TPI/DPI ratio; it also significantly increased the 32P-TPI/DPI ratio and decreased 32P-phosphoric acid incorporation into DPI but did not significantly affect 32P-phosphoric acid incorporation into TPI. Chronic ethanol administration is thought to have altered the turnover of phospholipids in the microsomal membrane, thereby affecting both the levels and turnover of neurotransmitters. In addition, the change of labeled TPI/DPI ratio observed after acute ethanol treatment may reflect nicotinic receptor activity in the mouse brain. PMID- 1449411 TI - Effect of acetaldehyde on ethanol absorption in the canine jejunum. AB - The effects of acetaldehyde on ethanol absorption from the intestinal tract were studied using canine jejunal segment. A thirty-centimeter jejunal segment with intact vascular supply was isolated, and jejunal absorption studies were performed by administering a 17% ethanol solution (0.4 g/kg) into the lumen of the jejunal segment. In the control group, blood ethanol concentrations in the portal vein increased rapidly, with a peak level of 9.8 +/- 1.9 mM 30 min after administration. In the cyanamide-pretreated group, dogs were injected intravenously with cyanamide (100 mg/kg), an inhibitor of acetaldehyde dehydrogenase, 150 min before ethanol dosing. The blood ethanol concentration in the portal vein of this group, accompanied by a high acetaldehyde concentration, increased gradually, reaching a peak of 10.7 +/- 1.84 mM 120 min after ethanol administration. Each concentration gradient corresponded to the systemic circulatory order from the portal vein for ethanol concentration, and from the hepatic vein for acetaldehyde concentration. The absorbed amount of ethanol in the control and cyanamide-pretreated groups was 94.9 +/- 4.1% and 69.3 +/- 4.8%, respectively. Pharmacokinetic analysis indicated that a presence of high acetaldehyde concentration in the blood resulted in less ethanol reaching the systemic circulation (control: 7.34 +/- 2.95 h-1, cyanamide-pretreated: 1.08 +/- 0.75 h-1). The results also suggest that the absorption of ethanol from the intestine decreases when there is a high acetaldehyde concentration in the blood. PMID- 1449412 TI - Ethanol enhances, but diazepam and pentobarbital reduce the ambulation-increasing effect of caffeine in mice. AB - The interactions of caffeine (10 mg/kg p. o.) with various doses of ethanol, diazepam or pentobarbital were investigated by observing the ambulatory activity of mice. The ambulatory activities after the coadministration of caffeine with ethanol (1.6, 2.4 and 3.2 g/kg p. o.) were significantly higher than those after the single administration of the corresponding doses of individual drugs. Ethanol alone significantly increased the activity with ataxia at 2.4 and 3.2 g/kg, suggesting that 1.6 g/kg of ethanol was an optimum dose for studying the interaction of caffeine with ethanol. Although diazepam (0.25, 0.5 and 2 mg/kg s. c.) and pentobarbital (1, 3 and 10 mg/kg s. c.) alone did not change the activity, they significantly reduced the effect of caffeine. Naloxone (1 and 5 mg/kg s. c.) did not modify the effect of caffeine alone, but, at 5 mg/kg, it was effective in significantly reducing the ambulation-increasing effect of caffeine with ethanol (1.6 g/kg) to nearly the level of caffeine alone. Ca-cyanamide (5 mg/kg p. o., pretreatment 30 min before), reserpine (1 mg/kg s. c., pretreatment 4 hr before) and alpha-methyl-p-tyrosine (200 mg/kg i. p., pretreatment 1 hr before) reduced the ambulation increment induced by caffeine alone or combination of caffeine with ethanol. Ethanol, diazepam and pentobarbital are classified as CNS depressants, and caffeine as a CNS stimulant. However, the present experiment demonstrated that the interaction of caffeine with ethanol was very different from that of caffeine with diazepam or pentobarbital. In the enhancing interaction of caffeine and ethanol, both dopaminergic and endogenous opioid systems may be involved. PMID- 1449413 TI - Patterns of alcohol abuse from the viewpoint of multiple substance abuse. AB - 1. As a result of examining the alcoholism of 172 subjects, from the view point of multiple abuse in a long-term process, we were able to classify alcoholism into three patterns: Pattern I is the alcohol alone type, Pattern II is the alcoholism with legal drugs, such as hypnotics and tranquilizers and Pattern III is the alcoholism with illicit drugs, such as organic solvents and methamphetamine. 2. We ascertained the alcohol alone abuse type (Pattern I) existed. 3. Pattern II resembles Pattern I in living status, delinquency, experience of criminal acts and characters except that the abusers in Pattern II were younger than those in Pattern I. 4. The abusers in Pattern III showed a trend to incline to multiple abuse. They had antisocial characters and family problems and the level of their social life was disrupted from their youth in many cases. PMID- 1449414 TI - [Alcohol drinking behavior based on the neurochemical background. I. Alcohol preference and brain monoamines]. AB - The relationship between voluntary alcohol consumption and monoamine levels was studied in the inbred strains of C57BL/6N, C57BL/6J, A/J, BALB/cA, CBA/N, C3H/He and DBA/2Cr mice; the congenic mouse strain B10. Br/Sg, and the senescence accelerated mouse (SAM P1, SAM P2). C57BL strains exhibited a high alcohol preference whereas the other strains exhibited a low alcohol preference. A clear positive relationship was found between alcohol intake (g/kg/day) and brain norepinephrine (NE) level (r = 0.683, p < 0.05), and a clear negative relationship between alcohol intake and brain serotonin (5HT) level (r = -0.628, p < 0.05). These results suggest that a voluntary alcohol intake in mice is genetically influenced with the brain monoamines, and depend upon the levels of brain NE and 5HT. PMID- 1449415 TI - [Alcohol drinking behavior based on the neurochemical background. II. Alcohol preference and aging]. AB - The present studies have investigated the relationship between alcohol behavior and aging in several strains of mice. First experiments have carried out whether a free choice of 10% (v/v) ethanol and tap water for 4 weeks changes the alcohol preference and the brain neurotransmitters in three inbred strains of mice, C57BL/6J, C3H/He and DBA/2Cr. Mice of these strains showed mean ethanol intakes of 4.41, 1.76 and 0.77 g/kg/day, respectively. Levels of the brain monoamines did not change in the alcohol preferring C57BL/6J mice, but in those with less preference of alcohol, C3H/He and DBA/2Cr, there were significant increases in dopamine and 5HT levels during the four weeks experiment. Second studies have reexamined if the factor of aging affects on the alcohol preference or drinking behavior in mice. Intake of 10% ethanol (ml/day) and alcohol preference (%) increased significantly with age. A further study was conducted in which groups of 16 week old mice were checked for alcohol preference along with a completely naive control group. The alcohol preference and alcohol intake were maximum in mice given free access to ethanol at 4 weeks of age. These results suggest that a) the mouse strain with a low preference of alcohol undergo neurochemical changes after exposure to 10% ethanol and water even be free choice, and b) alcohol drinking behaviors are not only affected on the general aspects but also the factor of aging and the conditions in which mice have expressed the accesses to alcohol. PMID- 1449416 TI - [Lymphocyte adenylate cyclase activity in alcoholics]. AB - Lymphocyte adenylate cyclase (AC) activity in alcoholics was examined. Gpp(NH)p stimulated AC activity was not altered in lymphocyte membranes from alcoholics in acute withdrawal state. In the case of long-term abstinent alcoholics, who maintained abstinence from alcohol for at least one year, lymphocyte Gpp(NH)p stimulated AC activity was slightly reduced but not significantly. However, the extent of AC activity induced by 250 mM ethanol in vitro, in the presence of Gpp(NH)p, was significantly reduced in lymphocyte membrane from long-term abstinent alcoholics. These results indicate that lymphocyte AC activity is a biological marker for alcoholics. PMID- 1449417 TI - Review of obstetric operative intervention rates. AB - The trends in obstetric operative intervention at a major teaching hospital in Sydney, Australia, were reviewed during the decade 1979-1989. While the caesarean section rate has increased by 36.4%, forceps deliveries have decreased. The normal delivery rate has remained constant at 67%. PMID- 1449418 TI - Umbilical artery blood flow in intra-uterine growth retarded fetuses and fetal outcome: a study of 102 cases. AB - The 102 fetuses diagnosed by ultrasound to be asymmetrically growth-retarded had blood flow velocity waveforms of the umbilical artery studied. Sixty-two cases had normal blood flow, 28 had abnormal blood flow but with present end-diastolic flow, 8 had absent end-diastolic flow, and 4 had reversal of end-diastolic flow. Comparison was made between the blood flow status and other biophysical methods of antenatal surveillance and perinatal outcome. There is a strong correlation between abnormal blood flow and abnormalities detected by other biophysical methods of antenatal surveillance. Our study shows that fetuses with severe blood flow impairment tend to be more severely growth-retarded and to be delivered earlier. Our results also show abnormal blood flow to be associated with a poor perinatal outcome. Those fetuses with severe impairment of blood flow suffered a high incidence of operative delivery for fetal distress, acidosis at birth, perinatal mortality and morbidity. The association between abnormal blood flow and the 5-minute Apgar score is significant only in those with the severest impairment of blood flow. Our results are in close agreement with similar studies recorded in the literature. PMID- 1449419 TI - Tetanic uterine contraction may be a cause of persistent fetal bradycardia after fetal blood sampling by ultrasound-guided cordocentesis. AB - Persistent fetal bradycardia necessiating emergency cesarean section is uncommon but a serious complication of ultrasound-guided cordocentesis. The cause of this complication, however, is not completely known. Reported here is a case of tetanic uterine contraction after fetal blood sampling via cordocentesis. PMID- 1449420 TI - Evaluation of measurement of fetal crown-rump length from ultrasonically timed ovulation and fertilization in vitro. AB - To assess with accuracy the development and maturity of the fetus, we evaluated fetal growth in 46 pregnant women who had conceived subsequent to ultrasonically timed ovulation. Fetal crown-rump length (CRL) was measured at gestational ages that differed by about 1 day from those previously reported. The variance in CRL measurements at each gestational age was small, and the data were normally distributed. The CRL growth curves of this and previous studies were tested using measurements from 7 pregnancies derived from in vitro fertilization (IVF). The data from IVF pregnancies were consistent with our curve, having 1 day difference to those previously reported. The gender of the fetus did not influence the CRL during the first trimester. The results suggest that fetal growth is uniform during the first trimester. PMID- 1449421 TI - Severe ovarian hyperstimulation syndrome with minimal ovarian enlargement: a case report. AB - Severe ovarian hyperstimulation syndrome is an uncommon but potentially lethal complication of treatment with in vitro fertilization and other assisted reproductive technologies. We describe such a case which was atypical in that ascites and hydrothorax occurred despite the absence of ovarian enlargement. Whilst the pathophysiology of the syndrome remains unclear, the clinician must remain alert to the possibility of such an unusual presentation of this syndrome. PMID- 1449422 TI - Assessment of follicular maturity by follicular diameter and fluid volume in a program of in vitro fertilization and embryo transfer. AB - We compared the assessment of follicular maturity by follicular diameter or follicular fluid (FF) volume and the subsequent fertilization and cleavage of the oocytes in 36 patients who had ovarian stimulation performed for in vitro fertilization and embryo transfer (IVF-ET). All patients received clomiphene citrate and human menopausal gonadotropin. The daily growth of follicles was assessed ultrasonically for 6 consecutive days before oocyte collection. The follicular diameter was found to be well correlated with the volume of follicular fluid. There were no significant differences among the dominant, second, and third follicles in the rates of oocyte recovery, maturation, fertilization, or cleavage. The rates of oocyte maturation and fertilization in FF volumes of 5.1 to 7.0 ml were significantly higher than in volumes of 1.1 to 5.0 ml, but the cleavage rates were similar. A smaller percentage of embryos developed to the four-cell stage when the oocytes were recovered from follicles with volumes of 1.1 to 3.0 ml. These observations suggest that follicular volume is a good parameter for judging the maturity of oocytes. It is also suggested that, although the oocytes of small follicles can be fertilized and cleaved, oocytes from larger follicles may have a better developmental capacity. PMID- 1449423 TI - Vulvar dystrophy: a clinical follow-up. AB - The vulvar dystrophy is an enigma and one of the most controversial topic as for the pathogenesis, clinical outcome and particularly the malignant potentiality. There has been very few systematic studies regarding vulvar dystrophy in Japan. Vulvar dystrophy with dysplasia is said to be a pre-malignant condition of the vulva. So in our institute a prospective follow-up of 5 months to 4 years was obtained in vulvar dystrophic patients after a conservative protocol of treatment. The initial histological diagnosis revealed 17 patients with squamous hyperplasia (9 patients with dysplasia and 8, without dysplasia), lichen sclerosus in 5 and other dermatoses in 1 patient. "Itching" was the most frequent complaint, encountered in 20 (69%) of the study patient. Amongst these patients 4/5 of lichen sclerosus and 16/18 of squamous hyperplasia and other dermatoses had complete symptomatic relief with testosterone and corticosteroid respectively. Morphologically 22/23 (96%) had more than 50% decrease of the total lesion. In squamous hyperplasia with dysplasia after treatment, the re-biopsy revealed improvement of the dysplasia in all the cases with total disappearance in the mild dysplasia group. So far, vulvar carcinoma did not develop in any of the patient followed in our study who received treatment for vulvar dystrophy. So, for vulvar dystrophy, a benign squamous epithelial disorder of the vulva, steroid hormone therapy is indeed a logical and a consistent one. PMID- 1449424 TI - Association between chlamydial infections and pelvic lesions. AB - Chlamydia trachomatis usually causes asymptomatic cervicitis, but it sometimes ascends into the uterine cavity, fallopian tubes, or peritoneal cavity, causing pelvic inflammatory disease and infertility. In this study, we examined endocervical chlamydial antigens and serum chlamydial antibodies in infertile women and laparoscopically evaluated pelvic lesions according to our pelvic scoring system. In patients testing positive for a chlamydial infection, the total pelvic score was significantly higher than in patients testing negative. When each area examined was assessed separately, however, only the tubal score was significantly higher in the chlamydia infected patients. These findings may indicate that tubal lesions are the major cause of infertility in women with chlamydial infections. PMID- 1449425 TI - Immunohistochemical and ultrastructural investigation of new membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) in gynecologic neoplasms. AB - New membrane-associated placental tissue proteins (MP2 A, B, C, D, and E) were investigated immunohistochemically by avidin-biotin immunoperoxidase technique and immunoelectron microscopy in various gynecologic neoplasms and normal gynecologic tissues. MP2 A and MP2 B were not specific for malignant tumors. MP2 C was present in 67-100% of ovarian carcinomas, 100% of benign dermoid cysts, and 77% of endometrial carcinomas. Except for endocervical adenocarcinomas, MP2 D was hardly detectable in gynecologic malignancies. Although MP2 E was hardly detectable in benign gynecologic tumors, this protein was present in ovarian carcinomas, uterine squamous carcinomas, endocervical adenocarcinomas, and endometrial adenocarcinomas. These results suggest a possible clinical application of these MP2 proteins as a new tumor marker for gynecologic malignancies. PMID- 1449426 TI - Vascular wall arachidonic acid metabolism and fetal growth in the pregnant STZ induced diabetic rat. AB - In pregnant women with severe diabetes mellitus, intrauterine growth retardation (IUGR) may occur despite hyperglycemia. Uterine blood flow may be an important factor in this process. Using pregnant streptozotocin-induced diabetic rats (pregnant STZ-diabetic rats), we evaluated functional and morphological changes in the endothelium, as well as platelet thromboxane A2 (TXA) production and their influence on uterine blood flow. Decreased basal endothelial prostacyclin (PGI2) production as well as significant attenuation of the production response to stimulus was noted, suggesting an impairment of PGI2 production. In the platelet, TXA2 production was augmented, leading to a hypercoagulable state. Decreased myometrial blood flow was documented. Scanning electron microscopy (SEM) revealed definite morphological abnormality of the endothelial cells, probably affecting the permeability to molecules, a major endothelial function. Based on these data, the endothelial derangements suggested by SEM and arachidonic acid metabolism alterations may affect fetal growth in the severe pregnant diabetic through alterations in uterine blood flow. PMID- 1449427 TI - The adverse effects of l-methamphetamine on the development of explanted rat embryos. AB - The adverse effects of l-methamphetamine on the development of rat embryos were studied by means of a whole culture system. The embryos explanted at 12.5th days of gestational age were cultured for a total of 24 hours. After pre-culturing for 6 hours, 4 groups of embryos received additional culturing for 18 hours with saline or various concentrations of l-methamphetamine; 0.5, 2.0 and 5.0 mumol/dl. There was no significant difference in the survival rate among 4 groups. The groups over 2.0 mumol/dl of l-methamphetamine showed significant reduction of crown-rump length, somite number, protein content, DNA content, and protein/DNA ratio. It is suggested that over 2.0 mumol/dl of l-methamphetamine reduces the development but not the survival of rat embryos under whole culture system. PMID- 1449428 TI - Amplification of nocturnal melatonin secretion in women with nocturnal hyperprolactinemia. AB - In order to assess the pathophysiological role of melatonin (MLT) in nocturnal hyperprolactinemia (NH), nocturnal serum MLT and prolactin (PRL) levels were measured in samples collected every 2h over a 12-hour period (2000h-0800h) from 5 normal women and 9 women with NH under physiological light/dark condition (lights off from 2100h to 0600h). Furthermore, differences in the PRL response to acute oral administration of MLT (1 mg or 5 mg) during the daytime between the 2 groups was studied. Nocturnal MLT levels in patients with NH were significantly higher (p < 0.02) than in normal women. The maximal PRL levels (52.6 +/- 26.7 ng/ml at 2400h) during the night in patients with NH were significantly higher (p < 0.05) and were reached 4h earlier than in normal women. The response to administration of 1 mg of MLT was not different between the 2 groups. However, administration of 5 mg of MLT to normal women resulted in a rapid and prominent PRL release, similar to that observed at nighttime in patients with NH. These results indicate that the abnormal PRL release in patients with NH is not due to higher sensitivity to MLT. However, the elevated MLT levels in patients with NH may be related to the neuroendocrine disorder. PMID- 1449429 TI - Effects of cochlear impairment and equivalent-threshold masking on psychoacoustic tuning curves. AB - Psychoacoustic tuning curves in simultaneous masking were measured in three groups: listeners with hearing impairment of primarily cochlear origin, normal listeners with equivalent-threshold masking (ETM) and normal listeners tested in the quiet. ETM was produced by presenting a continuous back-ground noise that was spectrally shaped to yield masked thresholds within 3 dB of each impaired listener's quiet thresholds. For the tuning curves, the level of a 50-Hz-wide noise band necessary to mask a 10-dB SL tone was measured for six masker frequencies. Results under ETM indicate that the shape of the tuning curve depends not only on masked threshold at the probe frequency but also on the spectral shape of the masker. Tuning curves are abnormally broad in some impaired listeners even when the effects of their elevated thresholds, audiometric configuration and altered intensity perception are taken into account by comparisons with normal listeners with ETM. PMID- 1449430 TI - Low-frequency specificity of the auditory brainstem response threshold elicited by clicks masked with 1590-Hz high-pass noise in subjects with sloping cochlear hearing losses. AB - In this study, the frequency specificity of the ABR threshold to stimulation with a click masked with 1590-Hz high-pass noise was determined in subjects with sloping cochlear hearing losses both high- and low-frequency in character. The results show that the ABR threshold elicited by this stimulus is low-frequency specific. The standard error in estimating the 1,000-Hz pure-tone threshold from the high-pass-noise-masked click-evoked ABR threshold is 10.2 dB which equals that for estimating the 3,000-Hz pure-tone threshold from the routinely used unmasked click ABR threshold. The ABR threshold elicited by a click masked with 1590-Hz high-pass noise can therefore be regarded as an accurate tool to predict the pure-tone hearing loss at 1,000 Hz. However, this method is less suitable for routine clinical testing because of the masking noise needed: the occasional high loudness level adversely affects the response quality and reduces the dynamic range of pure-tone hearing losses to be assessed. A third disadvantage is that determining the masking level electrophysiologically for each ear is time consuming. The search for a method with no or less masking noise should therefore continue. PMID- 1449431 TI - Comparison between the frequency specificities of auditory brainstem response thresholds to clicks with and without high-pass masking noise. AB - In this study, the frequency specificity of the auditory brainstem response (ABR) threshold to a click masked with 1590-Hz high-pass masking noise is compared with the frequency specificity of the unmasked click-evoked ABR threshold. The ABR threshold to the high-pass-noise-masked click stimulus is low frequency specific and corresponds with the 1,000-Hz pure-tone threshold. Although the ABR threshold to the unmasked click stimulus corresponds with the '3,000'-Hz pure-tone threshold, the frequency specificity seems much less pronounced than that of the low-frequency-specific stimulus. This study shows, however, that this apparent lack of frequency specificity can be attributed to the selection of pure-tone hearing losses. The ABR threshold evoked by an unmasked click stimulus is, therefore, preeminently useful as a high-frequency point of a two-point audiogram. The possible reasons why the ABR threshold evoked by a broad-band stimulus as the unmasked click corresponds with the higher frequencies of the pure-tone audiogram are discussed. PMID- 1449432 TI - Carboplatin and cisplatin ototoxicity in guinea pigs. AB - Ototoxic effects of cisplatin (1.5 mg/kg), cisplatin with mannitol (1.5 mg/kg cisplatin with 15 mg/kg mannitol) and carboplatin (6 mg/kg) were compared in guinea pigs treated 5 days a week for 5 consecutive weeks. Auditory thresholds were measured in awake animals by means of the compound action potential recorded from electrodes implanted near the round window. The endocochlear potential (EP) was measured in the first turn through the round window, and hair cell counts were estimated by the surface specimen technique. The most pronounced ototoxicity (threshold shifts and hair cell loss) was observed with pure cisplatin. Cisplatin with mannitol appeared to be less toxic than pure cisplatin, and carboplatin the least toxic. Even carboplatin produced significant threshold shifts, particularly at high frequencies, but they were not accompanied by hair cell loss. Values of EP were not different from those in normal control animals. PMID- 1449433 TI - Digital echocardiography in myocardial infarction. AB - Probably the most under-utilised application of echocardiography is in patients with coronary artery disease (CAD). This under-utilisation is striking since echocardiography can be very valuable in evaluating the natural history and therapy of CAD. One reason why echocardiography is not being utilised to its fullest is because of the reliance on videotape to record and display echocardiograms. This medium is time consuming and inconvenient for clinicians to review studies, it is not ideal for detecting subtle wall motion abnormalities, and videotape is impractical for comparing serial studies. Recording and storing echocardiograms on a digital medium overcomes these difficulties. Digital cine loops of single cardiac cycles provide great versatility. Multiple views or studies can be displayed simultaneously, subtle changes in wall motion are more easily detected and different views, or serial studies, can be readily compared. Such images can be displayed on computers on the ward or in the coronary care unit (CCU) and be available 24 hours a day, seven days a week at the convenience of the clinician. One does not need to find a recording on a two hour videotape, which may be in the ultrasound instrument, and one can view the exam in 30 sec instead of 5 to 10 min. Regional and global left ventricular function is one of the most important manifestations of CAD. With new therapeutic efforts at restoring myocardial function and limiting infarct expansion, assessing LV function is more important than ever. Digital echocardiography is an extremely practical and convenient way for clinicians to obtain this information. PMID- 1449434 TI - Transoesophageal echocardiography in heart disease--old technologies, new tricks. AB - Cardiac ultrasound and upper gastrointestinal endoscopy are relatively old technologies. With the introduction of new ultrasound probes and by incorporating ultrasound technology into conventional endoscopes, 'new tricks' in cardiac imaging were discovered. Posterior structures of the heart are now able to be imaged clearly by the ultrasound probe from the oesophagus. Consequently, better resolution of cardiac anatomy allows more accurate diagnosis of cardiac pathologies which is not possible using conventional transthoracic (TT) approach. Over a period of two years, 1200 cases of transoesophageal echocardiography (TOE) were undertaken in our institution. The major indications were diseases of the aorta (10%), source of cardioembolism (28%), assessment of native and prosthetic valve function (20%), suspected endocarditis and its complication (17%), pre and post percutaneous transluminal mitral valvotomy (PTMV [13%], congenital heart disease (2%) and others (10%). The greatest impact with TOE is in the diagnosis of aortic dissection and transection. TOE is superior to conventional TT approach in detecting potential source of embolism, valvular vegetations and its complication, native and prosthetic valve dysfunction and LA thrombus prior to PTMV. Observations by TOE such as spontaneous echo contrast (SEC) in the left atrium open new challenges for further research in its role in the pathogenesis of LA thrombus and its association with cardioembolic event. Other areas of interest include; reclassification of distal aortic dissection and the use of TOE in intra-operative work. PMID- 1449435 TI - Left ventricular energy in mitral regurgitation: a preliminary report. AB - Energy exchange based on Newtonian principles is the most appropriate way to express the function of any pump--including the heart. Using information obtained at cardiac catheterisation, we have measured the total work energy (ET) of the left ventricle (LV) (mean 1.63 F) in patients with severe mitral regurgitation (mean regurgitant fraction 0.66). ET was approximately 84% above normal. Of the regurgitant energy (RE) (mean 0.95 F), on average , 3/4 (73.6%) was kinetic (KE) and 1/4 (23.4%) potential (PE). Both components represent wasted LV energy: the kinetic energy associated with turbulence lost as heat, the potential energy responsible for a rise in Left Atrial (LA) pressure. The amount of PE as a percentage of total regurgitant energy (RE) varied considerably from one patient to another (10.5% to 54.4%). Hence, colour flow mapping which detects only KE of turbulent jet flow must underestimate LV energy loss and, because of patient to patient variation, cannot consistently reflect severity of regurgitation. Measurements of PE correlate well with wedge P-wave height. Corresponding non invasive estimates were made using sphygmodynamometer-calibrated indirect carotid pulse tracings and echocardiographic measurements. These were not significantly different from the invasive measurements. Unfortunately, the calculation of PE is indirect and involves subtraction, so that measurements for individual patients were not accurate enough for clinical use. Part of the non-invasive calculation involved an estimate of left atrial pressure based on the blood pressure measurement and Doppler velocity of regurgitation; this should be a useful measurement in itself.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449436 TI - Mitral valve billowing and prolapse--an overview. AB - Three decades after it was demonstrated that nonejection systolic clicks and late systolic murmurs have a mitral valve origin and that a specific syndrome is associated with the primary degenerative mitral lesion, numerous questions remain unanswered. A principal cause of confusion is the use of the term 'prolapse', which essentially implies a pathological state, in many patients with minimal evidence of a mitral valve anomaly. It should be recognised that no specific feature, whether evaluated by high standard echocardiography or indeed by careful morphological and histological examination, can be defined which distinguishes a normal variant from a pathological valve. There is a gradation from the normal billowing during ventricular systole of mitral leaflet bodies to marked billowing. With advanced billowing or floppy leaflets, failure of leaflet edge apposition supervenes (true prolapse). This is functionally abnormal and allows mitral regurgitation. Prolapse in turn may progress to a flail leaflet and hence gross regurgitation. Relatively rare complications of this degenerative mitral valve anomaly include systemic emboli, infective endocarditis, arrhythmias and, arguably, autonomic nervous system abnormalities. An attempt is made to clarify the management of some symptoms and other aspects of mitral prolapse-including rheumatic anterior leaflet prolapse (without billowing) which remains prevalent in South Africa and Third World countries. PMID- 1449437 TI - Echocardiography in the management of mitral valve prolapse. AB - Echocardiography plays a major role in the management of patients with mitral valve prolapse (MVP). The technique has greatly enhanced our understanding of the pathophysiology, epidemiology and natural history. There are major and minor echocardiographic diagnostic criteria for prolapse. Major criteria involve the mitral leaflets and include late systolic posterior displacement on M-mode, bulging into the left atrium on 2D long-axis (LAX) view, and thickening and redundancy of the leaflets. Minor criteria include holosystolic posterior prolapse on M-mode, bowing of the mitral leaflets into the left atrium (LA) in the apical 2D views, and late systolic mitral regurgitation on the Doppler echogram. Any of the major criteria should be sufficient to make the diagnosis. One or two minor criteria without a major sign would be questionable. The degree of thickening and redundancy and the presence and quantitation of mitral regurgitation influence prognosis. Echocardiography is also helpful in identifying complications such as endocarditis and ruptured chordae. An echocardiogram may not be necessary for the diagnosis, but it is helpful for prognosis and as a baseline for possible future changes. The frequency of follow up echocardiograms should be determined by clinical findings. When mitral regurgitation is present, then one should follow LA and left ventricular size and function. Transoesophageal echocardiography may be desirable for better definition of vegetations or flail leaflets and is frequently used to monitor surgical repair. PMID- 1449438 TI - Genes, gender and geometry and the prolapsing mitral valve. AB - Mitral Valve Prolapse (MVP) is usually a variant of normal occurring in about 4% of the population. Complications are relatively uncommon, but false associations due to ascertainment bias have had a potential for iatrogenic harm. Adverse outcomes which do occur in a subset of MVP subjects are considered here in relation to the contributions of genes, gender and geometry. There are definite associations between MVP and several dominantly inherited connective tissue abnormalities; it occurs in 85% of adults with Marfan syndrome. All these contribute to a very small proportion of the MVP population. A larger less easily characterised group with dominant inheritance and some features of a connective tissue disorder awaits DNA studies for identification. For most MVP subjects our data define significant family aggregation consistent with polygenic inheritance; the likelihood of a first degree relative having MVP is about two and a half times the population average. There is a higher prevalence in young women than in men-5% versus 3%; this has also been demonstrated for floppy mitral valve (MV) at autopsy. MVP complications of chordal rupture, severe mitral regurgitation and infective endocarditis are, however, two to three times more common in men, are age related and evident after the age of 50 years. Higher blood pressure in men may contribute to this in accordance with a response-to-injury hypothesis to explain progressive valve changes. Leaflet, annulus and left ventricular size differences and septal changes are geometric variants with a potential for increasing tension-related valve injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449439 TI - Mitral valve palpitations. AB - Few disorders ever provoked more interest and controversy than mitral valve prolapse (MVP). Past echocardiographic over-diagnosis led to it becoming a whipping boy for otherwise unexplained chest pain, palpitation, arrhythmias and emboli. Surgical centres reported a high incidence of endocarditis and severe regurgitation. Most investigators who have studied the prevalence of arrhythmias in MVP have concluded that they are more common in this syndrome than in the general population and that there is a causal rather than a fortuitous relationship. However, the prevalence of arrhythmias in reported studies is probably higher than in unselected MVP patients. Multiple ventricular premature beats, ventricular tachycardia and sudden death have been reported. Suggested mechanisms have included a focal cardiomyopathy with incoordinate contraction and relaxation, QRS dispersion, a long QT, traction on papillary muscles by prolapsed leaflets, interference with the blood supply of the papillary muscles, stimulation of the endocardium by the chordae and diastolic depolarisation of muscle fibres in redundant leaflets with triggered repetitive automaticity. MVP has been associated with pre-excitation giving rise to atrioventricular re-entry tachycardia. Autonomic dysfunction and a hyperadrenergic state has been claimed and this may also be responsible for supraventricular arrhythmias including atrioventricular nodal re-entry tachycardia, flutter and fibrillation. Electrophysiological studies have yielded contradictory results which may be due to the heterogeneity of the patients studied and variability of the mechanisms. Whatever the true prevalence, arrhythmias in MVP are usually benign. Syncope and sudden death are rare. Anti-arrhythmic therapy is only warranted in patients with frequent and distressing symptoms shown to be due to the arrhythmias or when arrhythmias are judged potentially life threatening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449440 TI - Optimising plasma lipids: public intervention versus high risk management. AB - A public health strategy carries more constraints than a high risk strategy because it targets both low risk and high risk individuals; this requires cautious intervention and hence achieves only a modest reduction in risk. Nevertheless, a modest population-wide fall in the concentrations of atherogenic lipoproteins leads to substantial numbers of preventable heart attacks and deaths. Other strategic considerations are to lower non-lipid cardiovascular risks (hypertension, clotting tendency) and to prevent other diet-related disease (such as cancer) through interventions which lower plasma lipids. The major nutritional changes which achieve this are optimising energy balance, reducing total fats and saturated fatty acids and increasing plant foods which are rich sources of unsaturated fatty acids, fibre and antioxidants. Each of these contributes to optimising the low density lipoprotein (LDL) concentration. Antioxidants (vitamins C and E mainly) may inhibit LDL oxidation. The strategy for lowering plasma triglyceride, especially in the context of atherogenic lipoprotein phenotypes, is mainly through energy balance, reduced saturated fat and alcohol. Correcting overweight especially in those with abdominal obesity, may normalise raised plasma triglyceride, low high density lipoprotein (HDL), abnormal LDL and even glucose intolerance and hypertension, which may be associated. The scientific basis for the lipid optimising effects of the different nutrients will be discussed. PMID- 1449441 TI - The Apo A, B, a of coronary risk: back to kindergarten. AB - Approximately 1% of the population have a dominantly inherited lipid disorder predisposing to premature vascular disease. Apolipoproteins (Apo) B, and A1, the carrier proteins for the atherogenic low density lipoprotein (LDL) and the protective high density lipoprotein (HDL) cholesterol respectively are markers for these disorders, as is Apo(a), the unique carrier protein for lipoprotein(a). We assessed changes in these apolipoproteins during the first 12 years of life, aiming to detect young families with inherited dyslipidaemia and implement early prevention. Among 1032 consecutively born babies in whom levels were measured within their first week and at a mean age of 8.5 months, the Apo B/A1 ratio and Apo(a) both tracked closely (p < 0.01 and < 0.0001). High B/A1 ratios (> 95 percentile) identified two families with familial hypercholesterolaemia, and infants with high Apo B identified two families with hyperapolipoprotein B. Apo(a) levels increased twofold between the first week and 8.5 months and were highly correlated (r = 0.73, p < 0.0001). Levels at 8.5 months were not different from parental values and were closely correlated with them. We then assessed school children aged eight to 12 years. In a pilot study (n = 1400) we have established normal apolipoprotein values and distribution patterns and defined the 95th percentile for each. This study is continuing and parents of children with high levels are being recalled (with their children) for lipid measurements. Our findings indicate that our approach is feasible and has wide acceptance, and that measuring Apo B/A1 and Apo(a) in childhood identifies families at increased cardiovascular risk. We have yet to assess the efficacy of our family-based coronary prevention programme. PMID- 1449442 TI - Cholesterol and coronary heart disease mortality. AB - The epidemiological relation between increased levels of blood cholesterol and increased risk of future heart disease is clear, both within and between countries. These strong relationships have led to the adoption of consensus statements in most countries which recommend measures such as the reduction of dietary saturated fat/an increase in the polyunsaturated/saturated ratio and other dietary and sometimes drug methods to reduce serum cholesterol. There is controversy as to whether these measures should be targeted at individuals with high levels of cholesterol or whether there should be a public health approach to the whole population. The public and medical debate has become more heated since the data from intervention trials are conflicting. Taken overall the trials do appear to show reduction in risk of coronary which is stronger for non fatal, compared with fatal coronary events. Meta analysis suggests that increasing benefit accrues from larger reductions and also longer reductions in cholesterol by intervention. However, individual trials frequently show variable results and some, especially the recent 15 year follow up of a Finnish five year intervention (by diet, cholesterol lowering and blood pressure lowering drugs) was strikingly adverse-although the total number of events was not large. Total mortality is much harder to influence and the sum of the available trials is hopelessly inadequate in size to address these questions. As a result confusion abounds and is unlikely to be clarified by the present on going trials. The need for more data is clear. The pilot study for the Oxford Cholesterol Study will be presented as a prelude for a proposed main study in about 20,000 high risk individuals. PMID- 1449443 TI - Lowering cholesterol: effects on trauma death, cancer death and total mortality. AB - Randomised trials of cholesterol reduction (26 trials, 50,000 patients, net cholesterol reduction approximately 10%) have demonstrated a clear reduction in the incidence of coronary heart disease (CHD) after just a few years of treatment. Overall, the reduction in CHD death was only half as large as the reduction in non-fatal myocardial infarction (MI), although both were statistically significant (2P < 0.005). In these trials, 60% of all deaths were from CHD, and since treatment reduced these by about 10%, the expected reduction in total deaths was about 6%. This expected reduction falls within the 95% confidence interval of the observed effect of cholesterol reduction on total mortality in these trials. There were small excesses of deaths from cancer and deaths from trauma among patients allocated active treatment. However, in no single trial, nor in the trials collectively, were these increases statistically significant. Furthermore, the increases did not appear to be specific to any one agent nor were the increases consistent between trials of the same agent. These observations are consistent with the hypothesis that the small excesses of cancer and trauma deaths observed in the cholesterol reduction trials occurred by chance. PMID- 1449444 TI - Trials and tribulations: the ISIS experience. AB - The ISIS trials group has grown slowly over the last ten years and now includes about 1000 collaborating hospitals worldwide. The original stimulus came from the thesis of a research student, Salim Yusuf, a newly qualified Rhodes Scholar from India. Yusuf's thesis (begun in 1976) examined methods of measuring infarct size quantitatively and paved the way to a preliminary trial of i.v. atenolol in 477 patients in Manchester and Oxford. Richard Peto was consulted about the statistical aspects of a trial design and pointed out that most clinical trials at that time were hopelessly inadequate in size to have the power reliably to ascertain the value of moderate but medically worthwhile treatments in many common conditions. We thus developed much larger collaboration, which still continues to grow. Dr Rory Collins joined the Oxford Cardiac Department and the CTSU in 1981 and now is the coordinator of the ISIS trials, and co-director with Richard Peto of the CTSU. Simple trials answer the questions rapidly and effectively. The mechanics of the trial do not hinder patient entry by participating doctors and nurses. The trials are mainly funded by industry, with 'priming' grants from the British Heart Foundation. Once the protocol is agreed the funding companies have no further input. The trials are planned and supervised by an international steering committee. Sir Richard Doll chairs the data monitoring committees. A brief overview of the three completed trials will be given, together with some peeps behind the scenes. PMID- 1449445 TI - The push, the pull and the periphery. AB - If the failing left ventricle could be given an effective push, other approaches to the treatment of heart failure would not be needed. We have inotropes only for short-term parenteral use. We have no safe inotrope for chronic oral use. The effect of digitalis is only feeble and the phosphodiesterase inhibitors seem to increase mortality from sudden death. Diuretics are dramatic for acute pulmonary oedema and the mainstay for chronic fluid retention but do not improve the pump and by reducing blood volume stimulate the renin angiotensin system to vasoconstriction, further fluid retention and hypokalaemia. Nitrates drop pre load without reducing blood volume but tolerance is a problem and stroke volume does not increase. Reduction of afterload helps the failing ventricle to empty, the pull and output increases. The angiotensin converting enzyme inhibitors (ACEI) are now the cornerstone of heart failure treatment, reducing mortality in severe heart failure (CONSENSUS) and superior to standard vasodilator therapy (V HeFT-2) at improving the survival of patients with mild to moderate heart failure. ACEI can reduce the incidence of ventricular ectopy and probably do this through improving left ventricular function, from decreasing sympathetic tone, reducing myocardial oxygen demand or increasing serum potassium but ACEI did not diminish the incidence of sudden death in the SOLVD trial despite reducing mortality. Disappointingly little improvement in exercise tolerance and persistence of chronic fatigue in heart failure concentrated attention on the periphery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449446 TI - Aspects of active rheumatic carditis. AB - Fulminating active rheumatic carditis has been observed for over 3 decades in this environment with no recent alteration in either the incidence or the pattern of presentation. Patients are black, seldom older than 20 years and are usually in their early teens but may occasionally be as young as five years. Heart failure is prevalent but occurs only when a haemodynamically important left-sided valve lesion supervenes. Regurgitation is the predominant valve lesion and involves principally the mitral valve. Mitral annular dilatation is the initial pathology and predisposes to lengthening--or rupture--of chordae tendineae and prolapse of the anterior leaflet. The resultant cardiac work-overload apparently perpetuates the rheumatic activity. Heart failure, whether caused by or associated with active rheumatic carditis, makes surgical management of the valve lesion mandatory as a life-saving measure. Mitral valve repair, rather than replacement, is the surgical procedure of choice but is not always practicable when the rheumatic activity is fulminant, significant aortic regurgitation associated or the surgeon relatively inexperienced. Aggressive medical therapy for heart failure, which should include vasodilator drugs, provides temporary improvement only. Contrary to ongoing doctrine, treatment with steroid drugs is neither life-saving nor beneficial. Varying degrees of left ventricular dysfunction are encountered pre-operatively and may be a sequel of the severe regurgitant valve lesion rather than of a rheumatic 'myocardial factor'. PMID- 1449447 TI - Remodelling of the heart after myocardial infarction. AB - In the first few hours after the onset of coronary occlusion the infarct zone stretches due to myocyte slippage. Subsequently the noninfarct zone develops volume overload hypertrophy with series addition of new sarcomeres and fibre elongation. Dilatation is detrimental as it increases ventricular wall stress and oxygen demand, and re-entry of electrical impulses may be influenced by stretching of the ischaemic scar resulting in ventricular fibrillation. Left ventricular remodelling and dilatation is a progressive process which begins early and continues in the months after infarction. The major determinants of the extent of remodelling are infarct size and patency of the infarct-related artery. Late reperfusion may reverse initial infarct dilatation and decrease left ventricular volumes by inducing calcium-activated contracture of the actomyosin complex. Expansion may also be inhibited by acceleration of healing, splinting of the infarct zone by salvage of subepicardial cells, and blood in the coronary arteries and veins supporting the infarct zone. End-systolic volume is the strongest predictor of long-term prognosis after infarction. A number of therapies including thrombolysis, angiotensin-converting enzyme (ACE) inhibition and nitrates have been shown to decrease left ventricular dilatation. The optimal time for commencement, dose, duration and the effects of combinations of therapy are yet to be determined. PMID- 1449448 TI - Exercise and the heart. PMID- 1449449 TI - Exercise echocardiography. AB - Exercise testing is an indispensable component of clinical cardiology. Latent disease or the full extent of a problem may not be apparent on a resting examination. Some form of stress is frequently necessary, especially in patients with coronary disease, to appreciate whether a patient has stress-induced ischaemia as manifested by exercise-induced chest discomfort, a drop in blood pressure or electrocardiographic changes of ischaemia. Unfortunately as with every test ECG and clinical monitoring have limitations. Patients may have ischaemia without pain, ECG changes may be non-specific, a resting abnormal ECG has limited value, and the location and amount of ischaemic muscle is not directly assessed. Monitoring the echocardiogram adds significant additional information to routine stress testing. By visualising the myocardium in the exercising individual, it is possible to assess a fundamental manifestation of ischaemia, regional wall motion abnormalities. This information helps identify the vessels and the amount of muscle involved. In addition resting wall motion abnormalities may detect clinically silent infarction or hibernating myocardium. Direct visualisation of the exercising heart provides an improved understanding of a patient's cardiac status. The technique is particularly useful in evaluating revascularisation procedures. Advances in instrumentation have reduced or eliminated many of the technical difficulties with obtaining and interpreting exercise echocardiograms. This examination has become an extremely useful adjunct to routine stress testing. PMID- 1449450 TI - Exercise testing? Not at all. AB - The traditional approach to the ambulatory patient with suspected or definite coronary disease is to evaluate the clinical features, to perform non-invasive tests for myocardial ischaemia, and to proceed, if necessary, to coronary angiography and coronary revascularisation. However, when the results of the exercise tests are discordant with the clinical classifications they are usually misleading as diagnostic tools. When the exercise test is used to assist prognostication, the information provided overlaps with that available to the clinician and only the presence of ST segment depression is an independent prognosticator. The amount of ST segment shift has been found to be an inferior prognosticator to the severity of disease seen on a coronary angiogram and the latter allows for appropriate decisions to be made regarding coronary angioplasty or bypass surgery. A more appropriate use of exercise testing is as a gate for coronary angiography if there is real doubt or the nature of the chest pain or as an aid in therapeutic decisions if the coronary angiography interpretation is difficult. PMID- 1449451 TI - The importance of assessing time-course behaviour of abnormal ST/T changes after exercise. AB - Routine stress electrocardiography has been criticised for yielding too many so called 'false-positive' results because ST/T changes that develop during and after exercise are prevalent. Recent studies in our institution indicate, however, that the time-course behaviour patterns of these ST/T configurational 'abnormalities' after exercise are different from those reflecting myocardial ischaemia due to epicardial coronary artery disease (CAD). Time-course analysis increases the predictive value of exercise testing and has dramatically decreased the number of asymptomatic subjects or symptomatic patients at low risk of having CAD being subjected to coronary arteriography in our institution. Our method of assessing post-exercise time course patterns of abnormal ST/T are described in detail. Ischaemic ST/T abnormalities have late onset, early offset or early onset, late offset whereas those ST/T changes associated with normal epicardial coronary arteries have late onset, late offset or early onset, early offset post exercise time course patterns. PMID- 1449452 TI - Heart failure: to digitalise or not? The view against. AB - Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy. PMID- 1449453 TI - Prevention of sudden cardiac death: the ICD, or an electrical end-point with preceding opportunities for intervention? AB - Sudden cardiac death (SCD) is usually due to monomorphic ventricular tachycardia and/or ventricular fibrillation. However, in the vast majority of patients these arrhythmias are associated with advanced structural disease. In our society, this is usually due to coronary artery disease (CAD). The implantable cardioverter- defibrillator is the logical approach to management in survivors of SCD. Its rational use must be guided by electrophysiology study. However, a realistic and cost-effective approach to the prevention of a first cardiac arrest must be multifaceted and take cognisance of other aspects including primary prevention. Limitation of the size of myocardial infarction (MI) is vital. Trials already suggests that effective thrombolysis may impinge long-term on arrhythmic end points. Following infarction, ventricular arrhythmias and sudden death may also be decreased by aspirin, beta-blockers, and possibly angiotensin converting enzyme inhibitors and amiodarone. Many post-infarction studies employ a combined end-point of death and clinical arrhythmias. However, death is usually confined to those with an ejection fraction < 35%. In them, treatment of associated heart failure is often a consideration and if the ejection fraction < 15-20%, depending on donor availability, transplantation may even be the preferred therapeutic option to the cardioverter-defibrillator. PMID- 1449454 TI - The automatic implantable defibrillator is the most realistic and cost-effective way of preventing sudden cardiac death. AB - Judgement about cost-effectiveness of medical treatments depends upon the criteria used to define effectiveness. The most rational single criterion is the Quality Adjusted Life Year gained (QALY). Comparisons of cost-effectiveness of treatments may be made by comparing the dollar costs per QALY. Both the dollar and the QALY comparisons are subject to all errors of biological variable measurement and bias introduced by experimental design seen in other biological experiments. The proper methodology for comparison is the prospective randomised controlled clinical trial. Such trials using the automatic implantable defibrillator (AICD) as prophylaxis against sudden cardiac death (SCD) have not yet been performed. The major underlying cause of SCD is coronary artery disease with previous myocardial infarction (MI) and provocative tests for ventricular arrhythmias are the most powerful predictors of SCD in infarction survivors. AICD implantation carriers a mortality of about 2%, and survival after successful implantation is about 89% at one, and 84% at two years. By comparison, infarction survivors with left ventricular ejection fraction < 0.4 and inducible slow monomorphic ventricular tachycardia have a survival rate of 70% at one, and 54% at two years. Antiarrhythmic drugs have not proven effective. There is an urgent need to confirm the advantage of the AICD by proper randomised controlled trial. PMID- 1449455 TI - Improved feed intake and body weight change in sheep treated with dexamethasone at entry into pens or feedlots. AB - Treatment with the synthetic glucocorticoid dexamethasone sodium phosphate increased the feed intake of sheep within 24 h. A single treatment with the longer-acting compound dexamethasone trimethylacetate had a slower effect, but resulted in improved feed intake and enhanced body weight gain over a period of 7 to 14 days. Treatment was effective in sheep housed individually and in sheep penned in groups. The improvement in body weight gain disappeared 15 to 20 days after a single treatment, but in most studies treated sheep had less variability in weight change than untreated sheep at this time. A statistically significant increase in body weight gain was observed in 8 of 11 trials; in the other 3 trials, it appeared that the feed intake of the untreated sheep was already maximal. Wethers treated with dexamethasone trimethylacetate on arrival at an assembly point for live export arrived in the Middle East 23 days later with a lower mean weight loss, partly because fewer sheep lost a significant amount of weight. PMID- 1449456 TI - Resistance to synthetic pyrethroid pour-on insecticides in strains of the sheep body louse Bovicola (Damalinia) ovis. AB - Groups of sheep infested with strains of Bovicola (Damalinia) ovis were obtained from flocks either with a history of failure to control lice with synthetic pyrethroid (SP) pour-on insecticides, or from farms where SP compounds were not used. The sheep were treated according to the manufacturer's recommendations with registered "off-shears" SP formulations. All treatments were applied under ideal conditions with doses calculated on an individual body weight basis and applied to the dorsal mid-line from the base of the neck to the butt of the tail. Treated sheep were kept in pens and maintained in separate groups. The pour-on SP treatments significantly reduced the lice population but failed to eliminate the infestation in 7 of 13 experiments in sheep carrying strains of lice with resistance factors of greater than 4 to at least one of the SP compounds. Failures occurred with all three of the SP pour-ons currently registered for lice control in NSW and with both water-based and organic solvent-based formulations. PMID- 1449457 TI - Production responses to internal parasite control in dairy cattle. AB - A significant increase in milk production, averaging 164 litres per cow per lactation (a 4.8% increase), was seen after cows infected with gastrointestinal nematodes, paramphistomes and Fasciola hepatica were treated with broad-spectrum anthelmintics. Three hundred and ninety pairs of cows from eight herds with year round calving were studied. One cow in each matched pair was given 7.5 mg/kg fenbendazole, 7.5 mg/kg levamisole hydrochloride and 15 mg/kg oxyclozanide in March, May and August of one year; the other cow in the pair received no anthelmintic. The number of nematode and trematode eggs was significantly decreased in the faeces of treated cows. PMID- 1449458 TI - Respiratory mechanics of horses during stepwise treadmill exercise tests, and the effect of clenbuterol pretreatment on them. AB - Normal Standardbred horses were given an incremental exercise test on a horizontal treadmill to evaluate the influence of exercise on gas exchange, resistance, dynamic compliance and inertance of the respiratory system. The exercise test consisted of 2 min exercise steps at each of the following speeds: 2.4 m/sec (walk), 4.5 m/sec (slow trot), 7.0 m/sec (fast trot) and 10 m/sec (gallop). At rest and after 1 min of exercise at each step, airflow, tidal volume, respiratory frequency, pharyngeal, mid-oesophageal and transdiaphragmatic pressures and arterial blood gas tensions were measured. The same horses were subsequently treated intravenously with clenbuterol (0.8 microgram/kg) and an identical exercise test and measurement performed 10 min after clenbuterol injection. In response to exercise, there were large increases in tidal volume, respiratory frequency, airflow and pressures. Exercise was associated with a decrease in upper airway resistance but total pulmonary resistance was unchanged. Exercise did not alter inertance or dynamic compliance, horses became hypoxaemic, and at 10 m/sec (galloping) also developed hypercarbia. Treatment with clenbuterol did not alter any of these measurements in response to exercise. These data suggest that dilation of upper airways occurs during exercise, and that inertial forces are important in strenuously exercising horses and may influence the accuracy of dynamic compliance determinations at high exercise intensities. PMID- 1449459 TI - Subclinical epitheliocystis in barramundi, Lates calcarifer, reared in sea cages. PMID- 1449460 TI - Pasteurella multocida septicaemia in pigs. PMID- 1449461 TI - Flood plain staggers, a tunicaminyluracil toxicosis of cattle in northern New South Wales. PMID- 1449462 TI - Total body water and the estimation of fat in the koala (Phascolarctos cinereus). PMID- 1449463 TI - An outbreak of fatal verminous pneumonia in cattle in north Queensland. PMID- 1449464 TI - Naturally occurring Eperythrozoon ovis infection in sheep reduces wool production. PMID- 1449465 TI - Isolation and characterization of two opioid peptides from a bovine hemoglobin peptic hydrolysate. AB - Two opioid peptides were isolated from a bovine hemoglobin hydrolysate, by use of gel permeation (GP) and reverse phase (RP) high performance liquid chromatography (HPLC). Their primary structure and accurate molecular weights, determined by amino acid analysis and fast atom bombardment (FAB) mass spectrometry, were identical to fragments 31-40 (LVV-hemorphin-7) and 32-40 (VV-hemorphin 7) of the beta-chain of bovine hemoglobin. The same fragments occur in human hemoglobin in positions 32-41 and 33-41 of the beta-chain, respectively. The opioid potency of these peptides, exhibited by use of electrically stimulated muscle of isolated guinea-pig ileum (GPI), were significant and comparable with some others previously described. In addition, the location of the two opioid peptides, VV hemorphin-7 and LVV-hemorphin-7, revealed the existence of a "strategic zone" both in the bovine and human beta-chains of hemoglobin. PMID- 1449466 TI - In vitro evolution of cisplatin/DNA monoadducts into diadducts is dependent upon superhelical density. AB - DNA binding of antitumor platinum(II) compounds accounts for cellular toxicity. Binding of cis-dichlorodiammineplatinum(II) (cis-DDP) to DNA involves the transient presence of monoadducts which evolve in a second phase into difunctional lesions which are far more toxic than the monoadducts. Temporal control of the monoadducts half-live is at least dependent upon the chemical nature of the cis-platinum derivative and the secondary structure of DNA. The effect of the degree of DNA superhelicity on the binding of cis-platinum derivatives as well as on the evolution of monofunctional adducts has been addressed on plasmid DNA. The rate of platination was not affected by the degree of DNA superhelicity. Similarly, when the evolution of the lesions was complete, no variation of toxicity was found with different populations of topoisomers, as determined by bacterial transformation efficiency. In contrast, when the kinetic of difunctional lesions formation was controlled in vitro, we observed a higher rate of formation on a supercoiled plasmid by comparison with a relaxed one. This result suggests that platinum-DNA adduct toxicity could be modulated by the topology of the chromosome. PMID- 1449467 TI - Biosynthesis of sphingolipids: dihydroceramide and not sphinganine is desaturated by cultured cells. AB - Radioactively labeled N-[1-14C]-octanoyl-sphinganine and D-erythro-[3-3H] sphinganine were administered in parallel experiments to neuroblastoma cells B 104. A time dependent formation of ceramide with a double bond in its sphingoid backbone was observed in both cases. In the presence of fumonisin B1 (25 microM), a strong inhibitor of sphinganine N-acyltransferase, desaturated ceramide was formed only when cells were fed with N-[1-14C]-octanoyl-sphinganine but not with [3-3H]-sphinganine. Thus, the introduction of the double bond occurs only at the level of dihydroceramide, after N-acylation of sphinganine. It is now obvious that sphingosine is not a biosynthetic intermediate but exclusively a catabolic product of cellular sphingolipids. PMID- 1449468 TI - Memory of butyrate induction by the Moloney murine sarcoma virus enhancer promoter element. AB - We reported previously that a housekeeping gene could be converted to a butyrate inducible gene by replacing its cognate promoter with the Moloney murine sarcoma virus enhancer-promoter element. In this study we report that the activated transcriptional state could be propagated from mother to daughter cells after the withdrawal of the inducer. PMID- 1449469 TI - Animal histo-blood group ABO genes. AB - Sequences homologous to the human histo-blood group ABO genes are present in the genomic DNA of various mammals. We have PCR-amplified, subcloned, and sequenced a portion of these genes from several species of primates and found high conservation of the nucleotide as well as the deduced amino acid sequences during evolution. PMID- 1449470 TI - The interaction of decorin core protein fragments with type I collagen. AB - To further define the molecular interaction between decorin and type I collagen we generated a 20 kD fragment containing the N-terminal half of the core protein by Endoproteinase Arg C digestion and a 40 kD fragment including all leucine-rich repeats in the central part of decorin core by cleavage with 2-nitro-5 thiocyanobenzoate. The fragments did not influence collagen fibril formation, even at high concentration, and radioactive fragments showed little binding to collagen fibrils. Our observations suggest that neither the N-terminal half nor the central leucine-rich repeats of the decorin core protein can, by itself, interact fully with fibrillar collagen. PMID- 1449471 TI - Phenylmethylsulfonyl fluoride stimulates proteolysis of nuclear proteins from chick liver. AB - The degradation of H1 histone and high mobility group (HMG) nonhistone proteins was stimulated when the homogenate from chick liver was incubated in the presence of phenylmethylsulfonyl fluoride (PMSF). Two proteinase inhibitors, elastatinal and chymostatin, significantly inhibited the PMSF-stimulated degradation of H1 histone and HMG proteins. On the contrary, other proteinase inhibitors like leupeptin, pepstatin, trypsin inhibitor, antipain, o-phenanthroline and EDTA had no effect on the degradation of the nuclear proteins. These results warn the researcher to be cautious while using PMSF for preparation of nuclear proteins such as H1 histone and HMG proteins. PMID- 1449472 TI - Brevinin-1 and -2, unique antimicrobial peptides from the skin of the frog, Rana brevipoda porsa. AB - Two unique antimicrobial peptides named brevinin-1 and -2 were isolated from the skin of the frog, Rana brevipoda porsa. Both of the peptides did not have any structural homology with bombinin nor magainin; the frog skin derived antimicrobial peptides isolated from Bombina and Xenopus, nor even with other known antimicrobial peptides of non-amphibian origin. The minimum inhibitory concentration of brevinin-1 against the growth of St. aureus and E. coli was determined to be 8 micrograms/ml and 34 micrograms/ml while that of brevinin-2 was 8 micrograms/ml and 4 micrograms/ml, respectively, indicating the difference of the two peptides in the antimicrobial selectively on Gram-positive and Gram negative bacteria. PMID- 1449473 TI - Therapeutic effects of superoxide dismutase derivatives modified with mono- or polysaccharides on hepatic injury induced by ischemia/reperfusion. AB - Therapeutic effects of four types of recombinant superoxide dismutase (SOD) derivatives, conjugates with polysaccharides, carboxymethyl (SOD-CMD) and diethylaminoethyl (SOD-DEAED) dextrans and galactosylated (Gal-SOD) and mannosylated (Man-SOD) derivatives, on hepatic ischemia/reperfusion injury were studied in rats. Hepatic injury induced by transient occlusion and subsequent reflow of hepatic blood was evaluated by the analysis of biliary excretion of bromosulfophthalein (BSP) injected intravenously. At a dose of 10000 units/kg, native SOD and SOD-DEAE did not show any significant effect and SOD-CMD showed slight effect. On the other hand, Gal-SOD and Man-SOD, targeted to the liver parenchymal and nonparenchymal cells, respectively, by a receptor-mediated endocytosis, exhibited superior inhibitory effects. These results demonstrated that these glycosylated SOD derivatives were useful for the prevention of hepatic ischemia/reperfusion injury. PMID- 1449474 TI - Identification of the fatty acid binding site on glutathione S-transferase P. AB - Glutathione S-transferase P (GST-P) bound a series of endogenous fatty acids (C12 C18). To clarify the function and the binding site of the fatty acids, interaction between fatty acids and GST-P was investigated by using 12-(9 anthroyloxy) stearic acid conjugated with Woodward's reagent K. The fluorescence conjugated fatty acid noncompetitively inhibited GST activity. After GST-P was covalently labeled with the fatty acid, the enzyme was digested with Lysyl Endopeptidase. From the peptide mapping, a single fluorescence-labeled peptide was obtained. By the sequence analysis, the peptide binding fatty acid was determined as the residues of 141-188 from the amino terminus. PMID- 1449475 TI - Dual role of S-nitrosocaptopril as an inhibitor of angiotensin-converting enzyme and a nitroso group carrier. AB - The S-nitroso derivatives of captopril can act as an inhibitor of an angiotensin converting enzyme in the presence of thiol such as glutathione. S Nitrosocaptopril also rapidly transfers its nitroso moiety to a heme protein, which is presumably the responsible mechanism for the activation of guanylate cyclase. These results suggest that S-nitrosocaptopril may serve as an effective hypotensive agent. PMID- 1449476 TI - Substrate preference of metalloproteinases secreted by ts-110 Moloney murine sarcoma virus-transformed normal rat kidney cells. AB - In this study, the two forms of affinity-purified transformation-associated proteins (TAPs) (68 and 64 kD) were shown to have different substrate preferences. For the 68-kD TAP, the order of substrate preference was collagen types I, III, and V; fibronectin; gelatin; and collagen IV. For the 64-kD TAP, the order of substrate preference was collagen I, III, and V and gelatin. The 64 kD TAP did not cleave collagen IV and fibronectin. We also found a 71-kD metalloproteinase in the concentrated purified TAPs that reacted only weakly with a TAP monoclonal antibody and showed this substrate preference: collagen I, III, and V; gelatin; and collagen IV. Whether this 71-kD TAP is a new member of the rat metalloproteinase family will be investigated. PMID- 1449477 TI - A receptor-binding peptide from human interleukin-6: isolation and a proton nuclear magnetic resonance study. AB - In order to locate the receptor-binding region of human interleukin-6 (IL-6), twelve peptide fragments were prepared by digestion of IL-6 with lysylendopeptidase. A significant activity of the receptor-binding was observed only for a peptide Ile88-Lys121, although the activity was estimated at 10(4) fold less than that of intact IL-6. Solution structure of the peptide Ile88 Lys121 was analyzed by using two-dimensional nuclear magnetic resonance (NMR) spectroscopy. The results indicate the presence of alpha-helices in the regions Leu93-Phe106 and Glu110-Ser119. On the basis of the NMR data, we also prepared two peptides. Four-fold less binding activity than that of the peptide Ile88 Lys121 was observed for the peptide Ile88-Arg105, but no activity for the peptide Glu110-Lys121. These results suggest that the helical peptide Ile88-Arg105 composes a part of the receptor-binding region. PMID- 1449478 TI - Invertebrate aspartyl/asparaginyl beta-hydroxylase: potential modification of endogenous epidermal growth factor-like modules. AB - An invertebrate alpha-ketoglutarate-dependent aspartyl/asparaginyl beta hydroxylase, which posttranslationally hydroxylates specific aspartyl or asparaginyl residues within epidermal growth factor-like modules, was identified, partially purified and characterized. Preparations derived from two insect cell lines catalyzed the hydroxylation of the expected asparaginyl residue within a synthetic epidermal growth factor-like module. This activity was found to be similar to that of the purified mammalian aspartyl/asparaginyl beta-hydroxylase with respect to cofactor requirements, stereochemistry and substrate sequence specificity. Furthermore, recombinant human C1r, expressed in an insect cell derived baculovirus expression system, was also found to be hydroxylated at the expected asparaginyl residue. Thus, these results establish the potential for invertebrate aspartyl/asparaginyl hydroxylation. Since several invertebrate proteins known to be required for proper embryonic development contain a putative consensus sequence that may be required for hydroxylation, the studies presented here provide the basis for further investigations concerned with identifying hydroxylated invertebrate proteins and determining their physiologic function. PMID- 1449479 TI - A Tat antagonist inhibits HIV-1 induction in naturally infected and experimentally infected T cells. AB - Ro 5-3335, a novel antagonist of human immunodeficiency virus type 1 (HIV-1) Tat activity, inhibits acute and chronic HIV-1 infection in T lymphocytes. Here we describe the effects of Ro 5-3335 on the accumulation of viral DNA during primary infection, the induction of virus from a latently infected cell line, and the expression of virus upon activation of naturally infected T cells. Ro 5-3335 permitted initial DNA synthesis during primary infection, but inhibited the subsequent increase in viral DNA copy number. The induction of HIV-1, as determined by the synthesis of p24 core antigen, was inhibited by 99% by Ro 5 3335 in both the model cell line and naturally infected T cells. PMID- 1449480 TI - Regulation by thyroid hormone of the synthesis of a cytosolic thyroid hormone binding protein during liver regeneration. AB - To understand the regulation by thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), of the synthesis of a cytosolic thyroid hormone binding protein (p58-M2) during liver regeneration, the synthesis of p58-M2 was evaluated. The synthesis of p58 M2 was measured by metabolic labeling of primary cultures derived from the regenerating liver of euthyroid, hypo- or hyperthyroid rats. During regeneration, the increase in the liver/body weight ratio is approximately 25% higher in hyper- than in hypothyroid rats. However, T3 has no effect on the rate of overall liver regeneration observed in four days. In mature liver, T3 increased the synthesis of p58-M2 by approximately 2.5-fold. During regeneration, however, the change in the synthesis of p58-M2 varied with the thyroid status. In euthyroid rats, the synthesis of p58-M2 continued to increase up to 2-fold during liver regeneration. In hyperthyroid rats, after an initial increase by 1.5-fold on day 1, the synthesis of p58-M2 subsequently declined during regeneration. In hypothyroid rats, the synthesis of p58-M2 remained virtually unchanged during regeneration. These results indicate that T3 regulates the synthesis of p58-M2 in mature and regenerating liver. PMID- 1449481 TI - Regulation of ATP-citrate lyase at transcriptional and post-transcriptional levels in rat liver. AB - The amounts of ATP-citrate lyase in liver cytosol began to increase at 12 hours after refeeding a high-carbohydrate diet and further increased until 48 hours. The amounts of the ATP-citrate lyase mRNA began to increase at 6 hours and reached to a maximum level at 12 hours, followed by decrease to a very low level until 48 hours. The elevated amount of the ATP-citrate lyase mRNA reflected on the increase of ATP-citrate lyase content in the first 24 hours, but these two parameters were not paralleled thereafter. The transcriptional activity of ATP citrate lyase gene in nuclei of rat liver began to increase at 4 hours and further increased to reach a maximum level of 24 fold at 12 hours, maintaining a high level of 17 fold until 48 hours. The elevation of transcriptional activity of ATP-citrate lyase gene preceded the increase of ATP-citrate lyase mRNA content in the liver cytosol by 2 hours, and its increasing pattern was similar to changes of mRNA content until 12 hours. However, while the transcriptional activity remained at a high level until 48 hours, the ATP-citrate lyase mRNA concentration in the cytosol decreased after 12 hours. PMID- 1449482 TI - Differentiative changes in fucosyltransferase activity in newborn rat epidermal cells. AB - An enzymatic activity catalyzing the transfer of L-fucose from GDP-L-fucose to a glycoprotein that is associated with the surfaces of the basal cells has been found in the membranous fraction of the cutaneous epidermis from the newborn rat. This fucosyltransferase which is located in the differentiated cells alters the acceptor glycoprotein's lectin-binding specificity from the Isolectin I-B4 of Griffonia simplicifolia (GS I-B4) to the Agglutinin I of Ulex europeus (UEA) and could be responsible for the same change in lectin-binding specificity that occurs as the epidermal basal cell differentiates. Another membraneous fucosyltransferase that can use asialofetuin--but not the GS I-B4-binding glycoprotein--as an acceptor, is also present in the membraneous fraction. PMID- 1449483 TI - Novel inhibitor of phospholipase A2 with topical anti-inflammatory activity. AB - Activation of a phospholipase A2 (PLA2) is a key step in the production of precursors for the biosynthesis of lipid mediators of inflammation. Inhibition of this enzyme could result in the suppression of three important classes of inflammatory lipids, prostaglandins, leukotrienes and platelet activating factor (PAF), and offers an attractive therapeutic approach to design novel agents for the treatment of inflammation and tissue injury. In this report we describe a novel compound, BMS-181162 4(3'-carboxyphenyl)-3,7-dimethyl-9(2",6"6"-trimethyl 1"-cyclohexenyl),++ +2Z,4E,6E, 8E-nonatetraenoic acid which specifically inhibits a 14 kD human PLA2 and effectively blocks phorbol ester induced skin inflammation in mice. BMS-181162 is the first reported specific inhibitor of PLA2 and its specificity may make useful tool in the dissection of the role of PLA2 in the inflammatory process. PMID- 1449484 TI - Methyl jasmonate conditions parsley suspension cells for increased elicitation of phenylpropanoid defense responses. AB - Pre-incubation of suspension-cultured parsley cells with methyl jasmonate greatly enhances their ability to respond to fungal elicitors by secretion of coumarin derivatives. The effect is most pronounced at relatively low elicitor concentration and also observed for the incorporation of esterified hydroxycinnamic acids and of "lignin-like" polymers into the cell wall. These three responses correspond to defense reactions induced locally when a fungal pathogen attacks plant cells. In contrast, the conditioning of parsley cells by the signal substance methyl jasmonate is reminiscent of the developmental nature of systemic acquired resistance and renders the cells more effective for the elicitor-induced local defense reactions. PMID- 1449485 TI - The glutathione conjugates of tert-butyl hydroquinone as potent redox cycling agents and possible reactive agents underlying the toxicity of butylated hydroxyanisole. AB - The glutathione conjugates of tert-butyl hydroquinone, a metabolite of butylated hydroxyanisole (BHA), possess redox potentials which are much higher as compared to the non-conjugated hydroquinone (0.36 V for the hydroquinone and 1.2-1.4 V for the conjugates). As a result, the redox cycling activity of the conjugates, as measured by oxygen consumption in the presence of a reducing agent, is increased tenfold as compared to the non-conjugated hydroquinone. Since evidence for both oxidative damage and the involvement for glutathione in the toxicity of butylated hydroxyanisole is available, this mechanism may be involved in the toxic action of this compound. PMID- 1449487 TI - Activation of an adrenergic pro-drug through sequential stereoselective action of tandem target enzymes. AB - The synthetic amino acid, 3,4-dihydroxyphenylserine (DOPS) has been of great interest for many years as an adrenergic pro-drug, since the L-threo diastereomer of DOPS can be a precursor of R-(-)-norepinephrine, the natural form of this neurotransmitter. We now report bioactivation of DOPS to the potent pharmacological agent, noradrenalone (arterenone), via sequential stereoselective action by two target enzymes--dopamine beta-monooxygenase (DBM) and L-aromatic amino acid decarboxylase (AADC)--acting in tandem. Enzymatic activation is stereospecific, with only the L-erythro DOPS diastereomer producing noradrenalone; this is consistent with the known stereospecificities of AADC and DBM. These results provide a heretofore unrecognized rationale for the bioactivity of L-erythro DOPS and provide a basis for the design of new adrenergic pro-drugs. PMID- 1449486 TI - Guanosine 5'-O-(3-thiotriphosphate) causes endothelium-dependent, pertussis toxin sensitive relaxations in porcine coronary arteries. AB - To determine whether direct stimulation of endothelial G-proteins causes relaxations of the underlying vascular smooth muscle, the effects of guanosine 5' O-(3-thiotriphosphate) (GTP gamma S) and sodium fluoride were studied in porcine coronary arteries and endothelial cells. Isometric tension was measured in coronary rings contracted with prostaglandin F2 alpha. GTP gamma S (in the presence of saponin) and sodium fluoride (in the presence of AlCl3) relaxed rings with, but not those without endothelium. The responses were inhibited by nitro-L arginine and pertussis toxin. In membrane fractions of coronary endothelial cells, GTP gamma S and sodium fluoride inhibited the ADP-ribosylation of G proteins catalyzed with [32P]-NAD and pertussis toxin. These data suggest that direct stimulation of G-proteins in endothelial cells by GTP gamma S and sodium fluoride causes a pertussis toxin-sensitive relaxation which may be attributed to the release of nitric oxide. PMID- 1449488 TI - Characterization of a Gly19-->Val mutant of ram p25, a low Mr GTP-binding protein: loss of GTP/GDP-binding activity in the mutated ram p25. AB - A substitution of Gly for Val at position 19, which corresponds to oncogenic Gly13-->Val mutation of ras p21, was introduced in a low Mr GTP-binding protein, ram p25. The protein was expressed in cytosolic fraction of Escherichia coli and purified by using specific antibody raised against ram p25. The mutated protein had no guanine nucleotide-binding activity although [Val13]ras p21 was reported to have. The analysis of guanine nucleotide composition of the purified [Val19]ram p25 revealed that the protein was free of nucleotide whereas the normal ram p25 bound about 1 mol of GDP per mol of protein. These results strongly suggested that some part(s) of variable regions as well as the consensus regions are important for the biochemical properties of ram p25. PMID- 1449489 TI - Prevalence of three mutations in the Gs alpha gene among 24 families with pseudohypoparathyroidism type Ia. AB - Pseudohypoparathyroidism type Ia (PHP-Ia), an inherited multi-hormone resistance syndrome, is associated with deficient cellular activity of the alpha-subunit of the guanine nucleotide-binding protein (Gs alpha) that stimulates adenylyl cyclase. We determined prevalence of three recently described mutations in exons 1 and 10 of the Gs alpha gene among 24 unrelated patients with PHP-Ia. Restriction analysis was used to detect two mutations that produce unique RFLPs, and allele-specific oligonucleotide hybridization was used to detect the other mutation. As none of these mutations were not found, genomic DNA was analyzed with denaturing gradient gel electrophoresis to screen for other mutations in exon 10. Mutations of the initiation codon and exon 10 in the Gs alpha gene thus rarely (< or = 4% each) cause PHP-Ia and the Gs alpha gene mutations causing PHP Ia are heterogeneous and unique to each pedigree. PMID- 1449491 TI - Re-examination of [3H]mepyramine binding assay for histamine H1 receptor using quinine. AB - [3H]Mepyramine, a potent antagonist of the histamine H1 receptor, has been widely used as a radioligand binding assay for the H1 receptor. Previously, we purified a mepyramine binding protein (MBP) from rat liver, but found that its partial amino acid sequences were very similar to those of debrisoquine 4-hydroxylase isozymes (P450 db1 and db2), which are members of the superfamily of cytochrome P450. Using cloned histamine H1 receptor cDNA, we found that [3H]mepyramine could bind only the H1 receptor and did not bind MBP in the presence of 10(-5) M quinine, an inhibitor of debrisoquine 4-hydroxylase isozymes. We developed a method to determine the contents of the H1 receptor and MBP separately using [3H]mepyramine and quinine and found that MBP is abundant in certain areas of bovine brain. PMID- 1449490 TI - DRG: a novel developmentally regulated GTP-binding protein. AB - Using a subtraction cloning approach we had previously isolated a series of murine cDNA clones representing the genes predominantly expressed in the embryonic brain and down-regulated during development. We now report that one of these cDNA clones encodes a novel type of GTP-binding protein. The predicted protein of 40.5 kD, named DRG, contains five structural motifs characteristic of the GTP-binding proteins. Consistently, bacterially expressed and cellular DRG proteins are capable of binding GTP in vitro. Sequences closely related to the DRG protein are found in other species including Drosophila and Halobacterium. Based on these observations, we propose that DRG represents an evolutionarily conserved novel class of GTP-binding protein which may play an important role in cell physiology. PMID- 1449492 TI - Immunocytochemical expression and localization of protein kinase C in bovine aortic endothelial cells. AB - Total PKC activity in BAEC incubated for 24 hrs in either 10% serum (FBS) or serum-deprived media (SDM) was similar. However, most of the activity (69%) in the FBS group was detected in the particulate fraction, while it was mainly in the cytosolic fraction (66%) in the SDM group. By confocal microscopy, there was diffuse cytoplasmic localization of the antibodies to the alpha and beta PKC isoforms. gamma PKC was not detected. Treatment of FBS or SDM cells with a phorbol ester resulted in an increase in PKC activity with translocation to the particulate fraction. PKC alpha immunofluorescence redistributed to the perinuclear region whereas PKC beta staining remained mostly cytosolic. Calphostin C, a PKC inhibitor, prevented the phorbol ester-induced increase in PKC activity and translocation. PMID- 1449493 TI - Molecular cloning of the mouse S-adenosylmethionine decarboxylase cDNA: specific protein binding to the conserved region of the mRNA 5'-untranslated region. AB - The nucleotide sequence of a cDNA encoding the proenzyme of mouse S adenosylmethionine decarboxylase (AdoMetDC) including 257 nucleotides of the 5' untranslated region has been determined. Comparison of the nucleotide sequence of the mouse 5' untranslated region with those of other mammals shows it to be highly conserved. The 52 nucleotides upstream from the translation initiation codon are identical in human, rat, bovine and mouse. The polyamines, spermidine and spermine, have been shown to inhibit AdoMetDC mRNA translation. An RNA gel retardation assay demonstrated that a cytoplasmic extract from mouse brain forms an RNA-protein complex with the completely conserved 5' untranslated sequence and that the complex formation is highly dependent on the presence of spermine. Crosslinking by UV irradiation shows that the complex contains a 39-kDa protein interacting with the 5' untranslated sequence. These data demonstrate spermine dependent specific protein binding to a highly conserved 5' untranslated region of an mRNA translationally regulated by polyamines. PMID- 1449494 TI - Modulation of transient type K channel cloned from rat heart. AB - We have cloned a transient type K channel from rat heart (RH10) and coexpressed a metabotropic glutamate receptor (mGluR5) to study the functional modulation of RH10 coupled to the phosphatidylinositol (PI) hydrolysis. Stimulation of mGluR5 suppressed peak amplitude of RH10 current and affected voltage dependence of activation and inactivation of the channel. PMID- 1449495 TI - 3H-uridine uptake in human leukemia HL-60 cells exposed to extremely low frequency electromagnetic fields. AB - Human leukemia HL-60 cells in vitro were exposed or sham-exposed to a 60 Hz electric (3.40 mV/m) or magnetic 10 G (1 muT) field for 5 hr in an attempt to replicate the results of a previously published report (1) of increased uptake of [3H] uridine in response to similar exposure conditions. The results of the present experiments indicated no treatment effect of the fields on uridine incorporation. The ability to detect differences in [3H] uridine uptake were confirmed in a negative control experiment. A 'negative control' experiment demonstrated a statistically significant increase in 3H-uridine uptake for cells at 37 degrees C relative to those at 4 degrees C. PMID- 1449496 TI - Purification and characterization of bovine brain gamma-aminobutyraldehyde dehydrogenase. AB - gamma-Aminobutyraldehyde dehydrogenase was purified to homogeneity from bovine brain. The molecular weight of the native enzyme and subunit were 230,000 and 58,000, respectively. The Km value for gamma-aminobutyraldehyde and NAD+ were 154 microM and 53 microM, respectively. The optimum pH and temperature were 8.0 and 37 degrees C, respectively. N-terminal sequence of the enzyme is as follows: NH2 S-A-A-T-Q-A-V-P-T-P-N-Q-Q-COOH. The enzyme migrates on isoelectric focusing with pI = 6.5. Enhancement of the enzyme activity by polyamine, Mn2+, Mg2+ and inhibition by gamma-aminobutyric acid and Zn2+ will enhance the limited information on regulation of the gamma-ABALDH activity and GABA metabolism to some extent. PMID- 1449497 TI - Regulation of the GTPase activity of the ras-related rap2 protein. AB - The small GTP-binding protein rap2A exhibits a high level of identity with rap1 and ras proteins (60% and 46%, respectively). Nevertheless, its intrinsic GTPase activity is not stimulated by ras-GAP, and unlike the rap1A protein, it cannot compete with ras proteins for their interaction with ras-GAP. In addition, rap1 GAPm that is highly active on the GTPase activity of the rap1A product, also stimulates the GTPase activity of the rap2A protein but with a 30-40-fold lower efficiency. An activity that greatly stimulated the GTPase activity of the rap2 protein (rap2-GAP) was found in bovine brain cytosol and purified. However, it copurified with the cytosolic form of rap1-GAP and was more efficient at stimulating the GTPase activity of the rap1 protein; this 55 kD polypeptide, that is recognized by an antibody raised against rap1-GAPm, likely represents a degraded and soluble form of the full size 89 kD molecule. In bovine brain membranes, a weak GAP activity toward the rap2A protein was also detected; however, it was also attributable to the membrane-associated rap1-GAPm. Thus, it appears that a single rap-GAP protein, complete or degraded, is able to stimulate the GTPase activity of both rap1 and rap2 proteins. PMID- 1449498 TI - Ethylbenzene hydroxylation by cytochrome P450cam. AB - The metabolism of ethylbenzene by cytochrome P450cam was analyzed by experimental and theoretical methods. The present experiments indicate that ethylbenzene is hydroxylated almost exclusively at the secondary ethyl carbon with about a 2:1 ratio of R:S product. Several molecular dynamics trajectories were performed with different starting conformations of ethylbenzene in the active site of P450cam. The stereochemistry of hydroxylation predicted from the molecular dynamics simulations was found to be in good agreement with the observed products. PMID- 1449499 TI - The COUP transcription factor (COUP-TF) is directly involved in the regulation of oxytocin gene expression in luteinizing bovine granulosa cells. AB - Competition with specific oligonucleotides in DNA-binding experiments, polyacrylamide gel electrophoresis, and recognition by specific antibodies have identified the ubiquitous transcription factor COUP as one of the nuclear proteins binding to the promoter region of the bovine oxytocin gene in endogenously expressing bovine granulosa cells. PCR cloning of partial cDNA sequences for bovine COUP-TF I and II and development of RNase protection assays demonstrated the up-regulation of COUP-TF in bovine granulosa cells and corpus luteum under conditions where the oxytocin gene is switched off. These experimental results from in vitro and in vivo studies point to the direct involvement of COUP-TF in oxytocin gene down-regulation during luteinization of bovine granulosa cells. PMID- 1449500 TI - A repressor region in the human beta-myosin heavy chain gene that has a partial position dependency. AB - Expression of the human beta-myosin heavy chain (beta MHC) gene was studied by transient assay in culture and in situ by direct injection of plasmids into adult rat hearts. In this report we describe a unique repressor region located -326/ 309 (5'-TTGGTGGTCGTGGTCAGT-3') of the human beta MHC gene that is conserved among the rat, rabbit, and human beta MHC genes. This sequence conferred repression onto heterologous promoters when the sequence was located 5' but not 3' to the promoters. This partial positional dependency suggests that the factor may act by limiting the binding of enhancers, located more proximally, to their DNA binding sites. PMID- 1449501 TI - Comparison of plasma levels of lipid hydroperoxides and antioxidants in hyperlipidemic Nagase analbuminemic rats, Sprague-Dawley rats, and humans. AB - The levels of lipid hydroperoxides and antioxidants in plasma samples from Nagase analbuminemic rats (NAR) and control Sprague-Dawley rats (SDR) were measured in comparison with those from normal human subjects. Cholesteryl ester hydroperoxide (CE-OOH) was detected, but phosphatidylcholine hydroperoxide was not. The levels of CE-OOH and the ratios of CE-OOH/CE were found to increase significantly in the order of human < SDR < NAR, suggesting that oxidative stress increases in the same order. NAR have a significantly lower level of ascorbate and lower ratio of ubiquinol/ubiquinone concentrations than SDR. This also suggests that NAR are subject to more oxidative stress than SDR, since ascorbate and ubiquinol are the most effective plasma antioxidants against oxygen radicals. PMID- 1449502 TI - Developmental change in subcellular location of Bp-1 protein with an ability to interact with both identifier sequence and its brain-specific transcript, BC-1 RNA. AB - Identifier sequences are transcribed to generate a brain-specific BC-1 RNA present as a ribonucleoprotein particle in the dendrites and somata of neurons. This ribonucleoprotein particle contains an identifier sequence-binding protein (Bp-1 protein). We report here the purification of BC-1 RNA and demonstrate that Bp-1 protein interacts directly with the RNA. We also demonstrate an accumulation of Bp-1 protein in the nucleus of brain cells from mouse fetus and newborns that precedes the postnatal increase in BC-1 RNA. Cytoplasmic Bp-1 protein present in a complex with BC-1 RNA increases postnatally with a concomitant decrease in nuclear Bp-1 protein. These observations suggest that Bp-1 protein may play a role(s) in the synthesis and nuclear export of BC-1 RNA. PMID- 1449503 TI - Gene structure of human indoleamine 2,3-dioxygenase. AB - Two genomic DNA clones that encode human indoleamine 2,3-dioxygenase (IDO) were isolated from the human genomic DNA library using the IDO cDNA as a probe, and their restriction maps and partial nucleotide sequences were determined. The human IDO gene spanned 15 kilobase pairs with ten exons. The 5' terminus of the IDO mRNA was 33 nucleotides upstream of the translation initiation codon ATG. The 5' flanking region contained ISRE, X-box, and Y-box like sequences. Southern blot analysis of the human genomic DNA indicated that the human IDO gene was present in a single copy in the genome. PMID- 1449504 TI - Circadian rhythm of covalent modifications in liver DNA. AB - 32P-postlabeling analysis recently revealed that in addition to 5-methylcytosine, mammalian DNA contains covalently modified nucleotides of unknown structures and functions termed I-compounds whose levels increase with age. I-compound levels, in addition, depend on species, strain, sex, tissue, and diet and are generally lowered by carcinogen exposure. As shown here, levels of several non-polar I compounds in liver DNA of untreated male C3H mice were elevated 2 to 8.5 times at 1800 h and 2400 h as compared to 0600 h and 1200 h, while polar I-compounds and persistent carcinogen-DNA adducts induced by safrole were unaffected by time of day. In liver DNA of male F-344 rats 4 non-polar I-compounds and 4 polar I compounds showed significant circadian rhythm at 2000 h compared to 0800 h. This novel circadian variation of DNA structure implies mechanisms precisely regulating I-compound levels in vivo and may conceivably be linked to diurnal differences of DNA synthesis and gene expression. PMID- 1449505 TI - Stimulation of glucose transport by guanine nucleotides in permeabilized rat adipocytes. AB - Effects of guanine nucleotides on glucose transport were studied in permeabilized rat epididymal fat cells. GTP gamma S and Gpp(NH)p, but not App(NH)p, stimulated 3-O-methylglucose transport. Effect of GTP gamma S was dose-dependent, being detectable at 0.1 mM, and 1.0 mM GTP gamma S stimulated glucose transport to the same extent as insulin. GTP gamma S (0.3 mM) enhanced insulin-stimulated glucose transport while 1 mM GTP gamma S did not affect insulin-mediated transport. GDP beta S had no effect on glucose transport by itself but rather enhanced insulin action. NaF, which is known to activate trimeric G proteins, increased glucose transport to the same extent as insulin. Likewise, mastoparan augmented glucose transport. These results indicate that a certain type of trimeric G protein(s) is involved in the regulation of glucose transport. PMID- 1449506 TI - Isolation and characterization of Y chromosome DNA probes. AB - A sorted, cloned Y chromosome phage library was screened for unique Y chromosome sequences. Of the thousands of plaques screened, 13 did not hybridize to radiolabeled 46,XX total chromosomal DNA. Three plaques were characterized further. Clone Y1 hybridized to multiple restriction enzyme fragments in both male and female DNA with more intense bands in male DNA. Clone Y2, also found in female and male DNA, is probably located in the pseudosutosomal region because extra copies of either the X or Y chromosomes increased Y2 restriction enzyme fragment intensity in total cellular DNA. Clone Y5 was male specific in three of four restriction enzyme digests although in the fourth a light hybridizing band was observed in both male and female DNA. Clone Y5 was sublocalized to band Yq 11.22 by hybridization to a panel of cellular DNA from patients with Y chromosome rearrangements. Clone Y5 can be used to test for retention of the proximally long arm Y suggested to cause gonadal cancer in carrier females. The long series of GA repeats in Y5, anticipated to be polymorphic, may provide a sensitive means to follow Y chromosome variation in human populations. PMID- 1449507 TI - Thapsigargin induces meiotic maturation in surf clam oocytes. AB - I report here that thapsigargin, an inhibitor of Ca(2+)-ATPase activities in internal Ca2+ stores, induces meiotic maturation in prophase I-arrested surf clam (Spisula solidissima) oocytes. The half-maximal dose for triggering germinal vesicle breakdown (GVBD) is 120 nM. Thapsigargin-induced GVBD is followed by all normal subsequent steps of meiotic maturation including extrusions of first and second polar bodies, with almost normal timing as compared with K(+)-induced activation. Thapsigargin-induced GVBD requires the presence of external Ca2+ at a half-maximal concentration of 0.6 mM. In normal sea water, thapsigargin-induced activation is accompanied by a slightly increased 45Ca2+ uptake by the oocytes and by an intracellular pH rise of 0.3 U. These results show that thapsigargin sensitive Ca2+ pools regulating Ca2+ fluxes exist in surf clam oocytes, and they also further establish that Ca2+ ions are the major initial trigger for meiosis resumption in this species. PMID- 1449508 TI - Stimulation of serum-free cell proliferation by coenzyme Q. AB - Coenzyme Q added to culture media stimulates the growth of HeLa and Balb/3T3 cells in serum free conditions. The stimulation by coenzyme Q is additive to the stimulation by ferricyanide, an impermeable electron acceptor for the transplasma membrane electron transport. alpha Tocopherylquinone can also stimulate cell growth, but vitamin K1 is inactive or inhibitory. The response to coenzyme Q and ferricyanide is enhanced with insulin. A contribution to plasma membrane NADH oxidation or modification of the membrane quinone redox balance can be a basis for the growth stimulation. PMID- 1449509 TI - Ergosterol depletion and 4-methyl sterols accumulation in the yeast Saccharomyces cerevisiae treated with an antifungal, 6-amino-2-n-pentylthiobenzothiazole. AB - In Saccharomyces cerevisiae treated with an antifungal agent, 6-amino-2-n pentylthiobenzothiazole, levels of ergosterol and other 4-desmethylsterols were found to be significantly reduced. Major sterols in treated yeast were lanosterol, 4,4-dimethylzymosterol, 4-methylzymosterol and 4-methylfecosterol. A hypothesis is stated that the antifungal agent inhibits sterol demethylation at C 4 and forces the biosynthesis to a blind pathway ending by 4-methylfecosterol. PMID- 1449510 TI - On the antioxidant effects of ascorbic acid and glutathione. PMID- 1449511 TI - Conversion of the human 5-HT1D beta serotonin receptor to the rat 5-HT1B ligand binding phenotype by Thr355Asn site directed mutagenesis. AB - The human 5-HT1D beta serotonin receptor and its rat homolog (also called the 5 HT1B receptor) share 93% amino acid identity, yet display markedly different pharmacological specificities. Comparison of deduced amino acid sequences among these and other recently cloned receptors suggested that this phenotypic difference might be attributable to a single human threonine355/rat asparagine351 amino acid difference in the putative seventh membrane spanning regions. We now report that Thr355Asn mutagenesis of the human 5-HT1D beta receptor alters the binding characteristics of the recombinant receptor in [3H]5-HT binding assays to a profile very similar to that of the rat 5-HT1B binding site. These results confirm that this single amino acid difference is responsible for the majority of the known pharmacological discrepancies between human and rat observed for 5-HT1D beta (5-HT1B) receptors. PMID- 1449512 TI - In vitro binding of oxime acetylcholinesterase reactivators to proteoglycans synthesized by cultured chondrocytes and fibroblasts. AB - The incorporation of the 14C-labelled acetylcholinesterase reactivators 1-(methyl imidazolium)-3 (4-carbaldoxime-pyridinium) propane dibromide (pyrimidoxime) and N,N'-trimethylene bis(pyridinium-4-aldoxime) dibromide (TMB4) into cultured chondrocytes and fibroblasts was measured and their binding to macromolecules synthesized by these cells studied. The results showed that these drugs concentrated slowly and poorly into these cells, but bound firmly to high molecular mass materials in the culture supernatants. The chromatographic properties of these macromolecules on Sepharose CL-2B in non-dissociative or dissociative conditions were similar to those of the proteoglycans synthesized by these cells. Dialysis of the macromolecule-bound drugs against increasing pH buffers showed half-dissociation pH > 8, identical to those for chondroitin sulphate. These results suggest strongly that pyrimidoxime and TMB4 are bound to proteoglycans by ionic interactions, and this together with their poor lipophilicity can explain their high selectivity for the cartilaginous tissues as opposed to other proteoglycan-containing structures such as skin. PMID- 1449513 TI - Quantitative structure-metabolism relationships for substituted benzoic acids in the rat. Computational chemistry, NMR spectroscopy and pattern recognition studies. AB - An extensive set of computed molecular properties, both steric and electronic, have been calculated using molecular orbital and empirical methods for benzoic acid (1) and a congeneric series of substituted benzoic acids, i.e. 2-, 3- and 4 fluorobenzoic acids (2-4), 2-, 3- and 4-trifluoromethyl benzoic acids (5-7), 2-, 3- and 4-methylbenzoic acids (8-10), 4-amino benzoic acid (11), 2-fluoro-4 trifluoromethyl benzoic acid (12), 4-fluoro-2-trifluoromethyl benzoic acid (13), 3-trifluoromethyl-4-fluorobenzoic acid (14). We have monitored the urinary excretion profiles and determined the metabolic fate of compounds 2-7, 12-14 in the rat using high resolution 1H and 19F NMR spectroscopy. Corresponding data for compounds 1,8-11 are taken from the literature. In all cases phase II glucuronidation or glycine conjugation reactions dominated the metabolism of these compounds. Compounds 5, 7, 12, 13 have ester glucuronides as their major metabolites; the rest primarily form glycine conjugates. Compounds (1-12) have been classified according to their calculated physicochemical properties using pattern recognition methods and principal components maps have been used as a novel type of structure-metabolism diagram. The maps of compounds in the physicochemical property space served to separate the compounds into the two major classes which related to their principal metabolic fate in vivo, namely glucuronidation versus glycine conjugation. Compounds 13 and 14 were used as further probes of the property space, and dominant metabolic fates of glucuronidation and glycine conjugation, respectively, were predicted from the previous "training set map". The metabolic fate of compounds 1-14 can thus be classified according to a simple set of physicochemical rules. Investigation of the physicochemical properties which are important in distinguishing the metabolic fate of the compounds may give insight into key features of the drug metabolizing enzyme active sites and hence provide information on basic mechanisms of benzoate metabolism. PMID- 1449514 TI - Inhibition of growth of human leukaemia 60 cells by S-2-hydroxyacylglutathiones and monoethyl ester derivatives. AB - S-2-Hydroxyacylglutathione derivatives were found to induce growth arrest and toxicity in human leukaemia 60 cells in culture. S-D-Lactoylglutathione was the most effective with a median inhibitory concentration IC50 of 82 microM (95% C.I. 65-105 microM). No similar toxicity was induced by reduced glutathione and/or the corresponding aldonic acid (500 microM) in human leukaemia 60 cells, nor by S-D lactoylglutathione (500 microM) in mature human neutrophils under the same culture conditions. Monoethyl ester derivatives of the S-2 hydroxyacylglutathiones were prepared and also induced growth arrest and toxicity but were less effective than the corresponding unesterified compounds. S-2 Hydroxyacylglutathione derivatives also inhibited the incorporation of [3H]thymidine into DNA early in the development of toxicity: for S-D lactoylglutathione, the median inhibitory concentration was 74 microM (95% C.I. 47-116 microM). The mechanism of the inhibition of human leukaemia cell growth by S-D-lactoylglutathione and other S-2-hydroxyacylglutathione derivatives is unknown but appears to be mediated by the inhibition of DNA synthesis. PMID- 1449515 TI - Accessibility of aminoglycosides, isolated and in interaction with phosphatidylinositol, to water. A conformational analysis using the concept of molecular hydrophobicity potential. AB - The mode of interaction between aminoglycosides and negatively charged phospholipids plays a critical role in the inhibition of lysosomal phospholipases induced by these antibiotics and therefore in their nephrotoxicity. Previous works suggested that accessibility of the drug interacting with phospholipids to water could be crucial in this respect. We have used the concept of molecular hydrophobicity potential described by Brasseur [J Med Chem 266: 16120-16127, 1991] to visualize the hydrophobic and hydrophilic envelopes around aminoglycosides assembled with phosphatidylinositol molecules, and to obtain a three-dimensional representation of the complex formed. Using a series of different aminoglycosides, we showed that molecules with a lower inhibitory potential (gentamicin B, amikacin and isepamicin) are surrounded by both hydrophobic and hydrophilic envelopes whereas aminoglycosides which are more inhibitory are enveloped primarily by either hydrophilic (kanamycin A or B) or hydrophobic (gentamicin C1a) envelopes. This approach, which is here for the first time applied to the study of drug-lipid complexes, could help in the better understanding of the molecular mechanism of lysosomal phospholipase inhibition induced by aminoglycosides. PMID- 1449516 TI - Influence of long-term ethanol treatment on in vitro biotransformation of benzo(a)pyrene in microsomes of the liver, lung and small intestine from male and female rats. AB - The influence of long-term ethanol exposure of rats on the microsomal biotransformation of benzo(a)pyrene [B(a)P] was studied. Male and female Wistar rats received an increasing amount of ethanol in their drinking water: percentages rose to 15% (w/v) in 3 weeks. The ethanol content was kept at a concentration of 15% for another 3 weeks. Livers, lungs and intestinal epithelial cells of the rats were then isolated and microsomal fractions prepared. In all organs, the metabolite most formed was 3-hydroxy-B(a)P. In the liver, males showed significantly higher B(a)P hydroxylase activity than females. On the basis of experiments using monoclonal antibodies, a significant part of the B(a)P biotransformation in male rat liver microsomes can be attributed to the male specific P4502C11. In the lung and intestine, there were no significant differences between the sexes. In the liver, ethanol treatment significantly decreased the microsomal formation of phenolic metabolites. In microsomes of intestinal epithelial cells, ethanol treatment enhanced the formation of phenols and diols. In conclusion, ethanol consumption by rats in moderate amounts leads to an alteration in the microsomal biotransformation of B(a)P. Effects are most prominent in the liver, where the formation of phenols is significantly decreased. PMID- 1449517 TI - DNA binding activity and inhibition of DNA-protein interactions. Differential effects of tetra-p-amidino-phenoxyneopentane and its 2'-bromo derivative. AB - In the present study are reported the differential DNA binding activity of the anti-tumor polyamidine tetra-p-amidinophenoxyneopentane (TAPP-H) and its 2'-halo derivative (TAPP-Br), and their effects on the binding of the recombinant Epstein Barr virus (EBV) nuclear antigen to a synthetic oligonucleotide mimicking the target DNA sequence present in the EBV genome. In addition, the proliferation kinetics and cell cycle analysis of human leukemia K562 cells treated with TAPP-H and TAPP-Br are reported. The possible in vivo relationship between DNA binding affinity and cytotoxicity is also discussed. PMID- 1449518 TI - Cyclosporin A protects hepatocytes against prooxidant-induced cell killing. A study on the role of mitochondrial Ca2+ cycling in cytotoxicity. AB - Cyclosporin A (CsA) is a potent inhibitor of the prooxidant-induced release of Ca2+ from isolated mitochondria. In this investigation, pretreatment of hepatocytes with CsA before exposure to the prooxidants tert-butyl hydroperoxide (tBH), cumene hydroperoxide or 3,5-dimethyl-N-acetyl-p-benzoquinone imine (3,5 Me2-NAPQI) prevented the loss of cell viability. HPLC analysis of adenine and pyridine nucleotide concentrations in hepatocytes treated with 3,5-Me2-NAPQI showed a rapid depletion of ATP prior to the loss of cell viability versus the maintenance of near control levels of ATP in hepatocytes treated with CsA before 3,5-Me2-NAPQI. In 3,5-Me2-NAPQI-exposed hepatocytes there was also a rapid loss of cellular NAD+ which could be accounted for initially by a transient increase in NADP+. Measurement of the intracellular Ca2+ pools showed an early depletion of the mitochondrial Ca2+ pool in hepatocytes exposed to 3,5-Me2-NAPQI, tBH or cumene hydroperoxide; this loss was prevented by CsA. In conclusion, these results show that CsA protected hepatocytes from prooxidant injury by preventing mitochondrial Ca2+ cycling and subsequent mitochondrial dysfunction. This suggests that in prooxidant injury, excessive Ca2+ cycling is an early and important event leading to mitochondrial damage and subsequently to cell death. PMID- 1449519 TI - Characterization of carbonyl reducing activity in continuous cell lines of human and rodent origin. AB - Carbonyl reduction was investigated in the continuous cell lines V79, NCI-H322 and C2REV7 by using the ketone compound metyrapone as a substrate. Metyrapone reducing enzymes were characterized by evaluating the cosubstrate requirement and by testing the sensitivity of this reaction to specific inhibitors. All cell lines were found to produce metyrapol at a linear rate over a time course of at least 48 hr, when tested in cultured monolayers. In general, cytosolic metyrapone reduction exceeds microsomal activity several-fold in all three cell lines. Quercitrin turned out to be the strongest inhibitor in all fractions, except in NCI-H322 microsomes where it had no effect. Consequently, carbonyl reductase is suspected to be responsible for metyrapone reduction in the cytosol and microsomes of V79 and C2REV7 cells as well as in the cytosol of NCI-H322 cells. Simultaneous sensitivity towards quercitrin, dicoumarol, indomethacin and 5 alpha dihydrotestosterone in some cases points to the existence of different isozymes of carbonyl reductase. In NCI-H322 microsomes only dicoumarol and indomethacin decrease metyrapol formation, thus pointing to an isozyme of NAD(P)H:quinone oxidoreductase. Concerning cosubstrate requirements metyrapone reducing enzymes show a strong preference for NADPH, thus confirming the involvement of carbonyl reductase in this reaction. In conclusion, carbonyl reduction of metyrapone in continuous cell lines is mediated by carbonyl reductases due to the common sensitivity towards the diagnostic inhibitor quercitrin and due to the strong preference for NADPH as cosubstrate. According to its maintenance in permanent cell lines carbonyl reductase seems to be an essential and constitutive enzyme, which probably fills an important role in normal cell physiology. PMID- 1449520 TI - Use of thiocarbamides as selective substrate probes for isoforms of flavin containing monooxygenases. AB - The oxidation of thiourea, phenylthiourea, 1,3-diphenylthiourea, 1,3-bis-(3,4 dichlorophenyl)-2-thiourea and 1,1-dibenzyl-3-phenyl-2-thiourea was measured in reactions catalyzed by purified pig liver flavin-containing monooxygenase (FMO-1) and by microsomal fractions isolated from pig, guinea pig, chicken, rat and rabbit tissues. The reactions, followed by measuring substrate-dependent thiocholine oxidation [Guo and Ziegler, Anal Biochem 198: 143-148, 1991], were carried out in the presence of 2 mM 1-benzylimidazole to minimize potential interference from reactions other than those catalyzed by isoforms of the flavin containing monooxygenase (FMO). While at saturating substrate concentrations the Vmax for purified FMO-1 catalyzed oxidation of all five thiocarbamides was essentially constant, velocities for the microsomal catalyzed reactions varied not only with tissue and species but also with the van der Waals' surface area of the thiocarbamide. Rat liver, rat kidney and rabbit liver microsomes failed to catalyze detectable oxidation of thiocarbamides larger than 1,3-diphenylthiourea and lung microsomes from a female rabbit only accepted substrates smaller than 1,3-diphenylthiourea. On the other hand, liver microsomes from chickens, pigs and guinea pigs catalyzed the oxidation of larger thiocarbamides, but the rates decreased with increasing substrate size and chicken liver microsomes showed no detectable activity with the largest thiocarbamide tested. To define more precisely the parameters affecting thiocarbamide substrate specificity of microsomal preparations, activities present in detergent extracts of guinea pig liver microsomes were separated into three distinct fractions. The substrate specificities of these partially purified fractions were different and consistent with the difference observed with microsomal catalyzed reactions. This strongly suggests that thiocarbamides that differ in size may be useful probes for measuring the number of activities of FMO isoforms in crude tissue preparations. PMID- 1449521 TI - Lipophilic amino alcohols with calcium channel blocking activity. AB - A series of novel lipophilic amino alcohols, analogs of the anticholinergic drug vesamicol, were evaluated for Ca2+ channel blocking activity. The effects of these drugs on depolarization-induced intracellular free Ca2+ concentration ([Ca2+]i) transients were examined in single NG108-15 cells and dorsal root ganglion (DRG) neurons in culture. [Ca2+] was recorded with the Ca2+ indicator Indo-1 and a dual emission microfluorimeter. Structure-activity studies indicated that features required for Ca2+ channel blocking activity were distinct from those required for anticholinergic activity. In particular, the Ca2+ channel blocking activity was insensitive to the configuration at the chiral center, whereas the anticholinergic activity was clearly enantioselective. One of the most active compounds, 3-(3-bromophenyl)-2-hydroxy-1-[1-(4 phenylpiperidinyl)]propane (2b), was characterized in more detail. This compound inhibited the dihydropyridine-sensitive Ca2+ channel response in NG108-15 cells, evoked by depolarization with 50 mM K+, with an IC50 of 5 microM. Field potential stimulation of DRG neurons elicited [Ca2+]i transients mediated by at least three Ca2+ channel subtypes; compound 2b inhibited the entire Ca2+ channel response with an IC50 of 1 microM. A key element required for Ca2+ channel blocking activity was the presence of an electron withdrawing substituent on the pendant phenyl ring. Modification of the amino alcohol structure may lead to more potent compounds with broad spectrum Ca2+ channel blocking activity. These structures provide a new chemical starting point for the development of Ca2+ antagonists. PMID- 1449522 TI - Glutathione S-transferase-dependent conjugation of leukotriene A4-methyl ester to leukotriene C4-methyl ester in mammalian skin. AB - The glutathione S-transferase (GST)-dependent conjugation of reduced glutathione (GSH) with leukotriene A4 (LTA4)-methyl ester in rodent and human skin was investigated. Incubation of [3H]LTA4-methyl ester (1 nmole, approximately 200,000 dpm) with cytosol prepared from rat, mouse and human skin or with affinity purified GST from rat skin cytosol in the presence of GSH resulted in the formation of LTC4-methyl ester. Maximum enzyme activity was observed in rat skin followed by mouse and human skin. With heat-denatured cytosol or in the absence of GSH, the product formation was negligible. GST purified from rat skin cytosol by GSH-agarose affinity chromatography exhibited a several-fold increase in the specific activity of enzyme with 1-chloro-2,4-dinitrobenzene (55-fold), ethacrynic acid (67-fold) and LTA4-methyl ester (12-fold) as substrates. Western blot analysis of the affinity purified GST indicated a predominant expression of the Pi class of GST isozyme followed by Mu and Alpha classes of isozymes. The formation of LTC4-methyl ester was established by its radioactivity profile on high pressure liquid chromatography and absorption spectroscopy. These results suggest that, in addition to xenobiotic metabolism, cutaneous GSTs may also be capable of metabolizing physiological substrates such as LTA4. PMID- 1449523 TI - Evidence for different mechanisms involved in the formation of lyso platelet activating factor and the calcium-dependent release of arachidonic acid from human neutrophils. AB - Recent studies suggest that the first step in platelet-activating factor (PAF) biosynthesis, 1-alkyl-2-lyso-GPC (lyso PAF) formation, may be initiated by the selective transfer of arachidonate from 1-alkyl-2-arachidonoyl-GPC to an acceptor lyso phospholipid by a CoA-independent transacylase activity (CoA-IT). The present study was designed to determine whether the formation of 1-alkyl-2-lyso GPC and the release of arachidonic acid can occur by different mechanisms. These experiments examined both the formation of 1-[3H]alkyl-2-lyso-GPC from 1 [3H]alkyl-2-acyl-GPC and the release of arachidonic acid from membrane phospholipids as determined by GC/MS in neutrophil homogenates under various conditions. The addition of unlabelled lyso phospholipids to neutrophil homogenates stimulated the time-dependent formation of 1-[3H]alkyl-2-lyso-GPC from 1-[3H]alkyl-2-acyl-GPC. Without exogenous lyso phospholipids, little 1 [3H]alkyl-2-lyso-GPC was formed in this reaction. The activity which catalyzed the formation of 1-[3H]alkyl-2-lyso-GPC had characteristics identical to CoA-IT as indicated by the fact that both reactions were: independent of Ca2+, Mg2+, CoA and CoA fatty acids, located in microsomal fractions, and stable in 10 mM dithiothreitol. In sharp contrast to the aforementioned reaction, addition of lyso phospholipids did not affect the quantity of arachidonic acid released from membrane phospholipids. Furthermore, there was a Ca(2+)-independent release of arachidonic acid from membrane phospholipid that was increased 4 to 5-fold after the addition of 5 mM Ca2+. Finally, Ca(2+)-dependent arachidonic acid release was inhibited by putative phospholipase A2 inhibitors, aristolochic acid and scalaradial, at concentrations where neither the production of 1-[3H]alkyl-2-lyso GPC nor Ca(2+)-independent arachidonic acid release was altered. Together these data imply that there may be different mechanisms involved in the formation of 1 alkyl-2-lyso-GPC and arachidonic acid from membrane phospholipids. PMID- 1449524 TI - Phosphorylation of 9-(2-phosphonomethoxyethyl)adenine and 9-(S)-(3-hydroxy-2 phosphonomethoxypropyl)adenine by AMP(dAMP) kinase from L1210 cells. AB - Acyclic nucleotide analogues 9-(2-phosphonomethoxyethyl)adenine (PMEA) and 9-(S) (3-hydroxy-2-phosphonomethoxypropyl)adenine ((S)-HPMPA) which display potent antiviral activity are transformed in the cells to their mono- and disphosphoryl derivatives. We purified from mouse L1210 cells the enzyme that in two steps phosphorylates PMEA and (S)-HPMPA to their diphosphoryl derivatives and found that it co-purifies with AMP(dAMP) kinase activity; the best substrates of this enzyme were AMP, ADP and dAMP. Other nucleoside 5'-triphosphates or creatine phosphate could not be substituted for ATP as a phosphate donor. Our results also indicated that at least one other enzyme (creatine kinase) is capable of transforming the monophosphoryl derivatives of the studied compounds to their respective diphosphates. PMID- 1449525 TI - Neurotoxins: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4 tetrahydroisoquinoline and 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline as substrates for FAD-containing monooxygenase of porcine liver microsomes. AB - The activity of FAD-containing monooxygenase (FMO) (EC 1.14.13.8) of porcine liver microsomes was examined with the neurotoxins, 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-6,7 dihydroxy-tetrahydroisoquinoline (MDTIQ), as substrates. FMO catalyses these neurotoxins. The kinetic parameters of FMO for the neurotoxins and electron donors were determined. Km values for MPTP, TIQ and MDTIQ were determined to be 47 microM, 6.9 mM and 5.6 mM, respectively. The Km for the electron donor, NADPH, was variable from 31 to 200 microM depending on the substrate used. The activities of FMO for these neurotoxins were comparable with that for dimethylaniline. PMID- 1449526 TI - Albumin binding and brain uptake of 6-fluoro-DL-tryptophan: competition with L tryptophan. AB - We investigated potential competition between L-tryptophan (TRP) and 6-fluoro-DL tryptophan (6-F-TRP) for binding to albumin and for passage through the blood brain barrier (BBB). In experiments based on equilibrium dialysis, albumin (600 microM) bound about 80% of TRP and 50% of 6-F-TRP with affinity constants (Ka) of 3.7 +/- 0.04 x 10(4) and 0.62 +/- 0.01 x 10(4) M-1, respectively. Competitive inhibition was assessed as the decrease in the apparent Ka (K' a) of TRP in the presence of 6-F-TRP, with no modification of the N value. Competition between TRP, 6-F-TRP and L-valine (VAL) for passage across the BBB was demonstrated using two approaches. When administered concomitantly with TRP or 6-F-TRP to rats, VAL decreased brain uptake of TRP and 6-F-TRP and reversed their action on serotonin. In Oldendorf's model, 6-F-TRP and VAL decreased the brain uptake of TRP. PMID- 1449527 TI - Fasting in the rat does not induce hyperfibrinogenaemia. AB - The effects of fasting in the rat on the plasma fibrinogen concentration have been investigated. Fasting for 24-48 hr produced the expected sustained increase (4-5-fold) in the concentrations in the plasma of non-esterified fatty acids, but no accompanying increase in that of fibrinogen was detected. PMID- 1449528 TI - Inhibition of adenosine deaminase by azapurine ribonucleosides. AB - We have synthesized several 8-azapurine nucleosides as inhibitors of adenosine deaminase. The presence of a nitrogen on the imidazole ring decreased the Ki value for nebularine by 100-fold but did not lower the Ki value for coformycin. Evaluation of these compounds in a MOLT-4 growth assay revealed that 2 azacoformycin was as effective as 2'-deoxycoformycin in potentiating growth inhibition by 2'-deoxyadenosine. The azapurine nucleosides merit further study as antitumor agents. PMID- 1449529 TI - Inhibition by a novel azole antifungal agent with a geranyl group on lanosterol 14 alpha-demethylase of yeast. AB - AFK-108 (1-[2-(2,4-dichlorophenyl)-2-((2E)-3,7-dimethylocta-2,6- dienyloxy)ethyl] 1H-imidazole) is a new imidazole derivative characterized by a geranyl substituent showing strong antifungal activity. Azole antifungal agents are known to be potent inhibitors of lanosterol 14 alpha-demethylase (P450(14)DM) of fungi. The role of the geranyl group of AFK-108 on interaction of AFK-108 with the target was studied by using Saccharomyces cerevisiae P450(14)DM as the model enzyme. AFK-108 and some of its derivatives bound to oxidized P450(14)DM with one to-one stoichiometry and inhibited the demethylase activity. AFK-108 derivatives having the longer farnesyl or the shorter prenyl group showed lower affinity than AFK-108 for the enzyme. AFK-108 caused 100% inhibition at the equivalent concentration to P450(14)DM in the reaction mixture (0.07 microM), while the farnesyl derivative inhibited the activity by 60% at the same concentration. AFK 108 interfered with the binding of CO to the ferrous P450(14)DM. However, the interfering effect of the prenyl derivative was lower than that of AFK-108. Another AFK-108 derivative having the saturated 3,7-dimethyloctyl group was also a weaker inhibitor than AFK-108. These experiments suggest that the geranyl group of AFK-108 interacts with the substrate binding site of P450(14)DM that recognises the side chain of the substrate. AFK-108 is the first example of an azole derivative interacting with the side chain recognising region of the substrate binding site of P450(14)DM. PMID- 1449530 TI - Oxidative dehalogenation of 2-fluoro-17 alpha-ethynyloestradiol in vivo. A distal structure-metabolism relationship of 17 alpha-ethynylation. AB - Metabolic activation to catechols and their oxidation products is variously considered to contribute to the genotoxic, cytotoxic, transforming and tumour promoting activities of exogenous steroidal oestrogens. 2-Fluoro-17 alpha ethynyloestradiol (2-FEE2) was synthesized as a prototype of pharmacologically active derivatives of 17 beta-oestradiol which are resistant to metabolic activation in vivo. It possessed high affinity for the rat uterine oestrogen receptor and was oestrogenic in rats. Biliary metabolites of [6,7-3H]2-FEE2 (0.73 mumol/kg, 157 micrograms/kg, i.v.) in female rats were characterized: 87% of the radiolabel was excreted, principally as 2-FEE2 glucuronide, over 6 hr. Although 2 fluoro-17 beta-oestradiol is not metabolized to C-2 oxygenated products in vivo, 2-FEE2 underwent rapid and appreciable oxidative defluorination. 2-Hydroxy-17 alpha-ethynyloestradiol and 2-methoxy-17 alpha-ethynyloestradiol represented, respectively, 8% and 13% of the dose. Fluorination nevertheless restricted C-2 oxygenation to ca. 28% of that which 17 alpha-ethynyloestradiol undergoes in female rats. C-4 oxygenation of 2-FEE2, resulting in catechol formation, occurred but to a lesser extent (ca. 12% of dose). None of the major and identified minor biliary metabolites was a product of metabolic activation at the ethynyl function. A mechanistic rationalization of the long range enhancement by 17 alpha ethynylation of oxidative defluorination at C-2 is presented. PMID- 1449531 TI - Potentiation of CB 1954 cytotoxicity by reduced pyridine nucleotides in human tumour cells by stimulation of DT diaphorase activity. AB - The toxicity of CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] towards human cells was greatly enhanced by NADH (when foetal calf serum was present in the culture medium) and by nicotinamide riboside (reduced) (NRH), but not by nicotinate riboside (reduced). Co-treatment of human cells with CB 1954 and NADH resulted in the formation of crosslinks in their DNA. The toxicity produced by other DNA crosslinking agents was unaffected by reduced nicotinamide compounds. When caffeine was included in the medium, a reduction in the cytotoxicity of CB 1954 occurred. The toxicity experienced by human cell lines after exposure to CB 1954 and NADH was proportional to their levels of the enzyme DT diaphorase NAD(P)H dehydrogenase (quinone), EC 1.6.99.2. It is concluded that NRH, which we have shown to be a co-factor for rat DT diaphorase (Friedlos et al., Biochem Pharmacol 44: 25-31, 1992), is generated from NADH by enzymes in foetal calf serum, and stimulates the activity of human DT diaphorase towards CB 1954. PMID- 1449532 TI - Nature of cytochromes P450 involved in the 2-/4-hydroxylations of estradiol in human liver microsomes. AB - Kinetics of the 2- and 4-hydroxylations of estradiol (E2) by human liver microsomal samples were studied to determine the major P450 isoform involved in these endogenous reactions. Thirty human liver microsomal samples were analysed. Metabolism of 25 microM [14C]E2 produced 2-hydroxy and 4-hydroxy derivatives with a ratio of 3.2 +/- 1.5 and a great inter-individual variation. Kinetic analysis of the 2- and 4-hydroxylations of E2 exhibited a curvilinear double reciprocal plot with an apparent Km of 15 microM. Further experiments demonstrated that alpha-naphthoflavone, testosterone and progesterone increased the 2-hydroxylation activity, suggesting the involvement of a substrate activation mechanism. These two hydroxylations of E2 were shown to be catalysed by cytochrome P450 with an apparent dissociation constant Ks of 0.8 microM. These 2- and 4-hydroxylations inter-correlated significantly (r = 0.93; N = 30). The 2-hydroxylation of E2 correlated with four monooxygenase activities known to be supported by P450 3A4/3A5, namely nifedipine oxidation (r = 0.78; N = 29); erythromycin N demethylation (r = 0.69; N = 27), testosterone 6 beta-hydroxylation (r = 0.66; N = 25) and tamoxifen N-demethylation (r = 0.64; N = 29). On the other hand, E2 hydroxylations did not correlate with activities supported by P450 1A2 and P450 2E1. Furthermore, drugs as cyclosporin, diltiazem, triacetyl-oleandomycin and 17 alpha-ethynylestradiol inhibited more than 90% of the E2-hydroxylations at concentrations < 250 microM, while weak inhibition was shown with 500 microM cimetidine and no significant inhibition with caffeine, phenacetin and omeprazole. Finally, 2- and 4-hydroxylations of E2 correlated significantly with the content of P450 3A4/3A5 immunodetected by a monoclonal antibody anti-human P450-nifedipine (r = 0.84; N = 28). E2-hydroxylation activities were inhibited by more than 80% with polyclonal anti-human anti-P450-nifedipine. Preincubation of human liver microsomes with 100 microM gestodene (a suicide substrate of P450 3A4) inactivated this P450 isoform and accordingly allowed evaluation of the contribution of other P450 isoforms to the E2 metabolism to about 21% (+/- 17%, N = 29). All these results taken together suggest that P450 3A4/3A5 are the major forms involved in the formation of catecholestrogens in the human liver microsomes. PMID- 1449533 TI - Protein-specific S-thiolation in human endothelial cells during oxidative stress. AB - Confluent human umbilical vein endothelial cells were treated with diamide, t butyl hydroperoxide (t-BH) or the hydrogen peroxide generating system glucose/glucose oxidase and the effects on glutathione oxidation and protein S thiolation were examined. In the presence of all three oxidants glutathione was rapidly oxidized to a similar extent and S-thiolation of a limited number of proteins occurred. Diamide caused considerable S-thiolation of proteins with molecular masses of 44, 34, 24 and 14 kDa, of which the protein with molecular mass of 44 kDa was most extensively modified. t-BH caused extensive modification of proteins with molecular masses of 24 and 14 kDa whilst hydrogen peroxide caused S-thiolation of proteins of 39, 24 and 14 kDa. This study shows that S thiolation of proteins is an important metabolic response to oxidant insult in human endothelial cells and that the specificity of the response depends on the chemical nature of the oxidant. PMID- 1449534 TI - Protective effect of trifluoperazine on the mitochondrial damage induced by Ca2+ plus prooxidants. AB - Isolated rat liver mitochondria undergo extensive swelling and disruption of membrane potential when they accumulate Ca2+ in the presence of a prooxidant such as diamide or t-butylhydroperoxide. The phenothiazinic drug trifluoperazine, at concentrations (15-35 microM) which do not inhibit respiration or the influx of Ca2+ into mitochondria, significantly protected mitochondria against the deleterious effects of Ca2+ plus a prooxidant. In contrast, at concentrations higher than 100 microM the drug potentiated these deleterious effects of Ca2+ and prooxidants and had a damaging effect per se on the inner mitochondrial membrane. It is proposed that the protection conferred by the drug is mediated by changes in membrane protein structure that decrease the production of protein thiol cross linkings which occur when mitochondria accumulate calcium under oxidant stress conditions. PMID- 1449535 TI - Enalapril hepatotoxicity in the rat. Effects of modulators of cytochrome P450 and glutathione. AB - The effects of modulators of cytochrome P450 and reduced glutathione (GSH) on the hepatotoxicity of enalapril maleate (EN) were investigated in Fischer 344 rats. Twenty-four hours following the administration of EN (1.5 to 1.8 g/kg), increased serum transaminases (ALT and AST) and hepatic necrosis were observed. Pretreatment of the animals with pregnenolone-16 alpha-carbonitrile, a selective inducer of the cytochrome P450IIIA gene subfamily, enhanced EN-induced hepatotoxicity, whereas pretreatment with the cytochrome P450 inhibitor, cobalt protoporphyrin, reduced the liver injury. Depletion of hepatic non-protein sulfhydryls (NPSHs), an indicator of GSH, by combined treatment with buthionine sulfoximine (BSO) and diethyl maleate (DEM) produced marked elevations in serum transaminases by 6 hr after EN treatment. Administered on its own, EN decreased hepatic NPSH content and when combined with the BSO/DEM pretreatment, the liver was nearly completely devoid of NPSHs. Protection from EN-induced hepatotoxicity was observed in animals administered L-2-oxothiazolidine-4-carboxylic acid, a cysteine precursor. Together, these observations suggest the involvement of cytochrome P450 in EN bioactivation and GSH in detoxification. The results corroborate previous in vitro observations pertaining to the mechanism of EN induced cytotoxicity towards primary cultures of rat hepatocytes. Although the doses of EN used in this study were far in excess of therapeutic doses, under certain circumstances, this metabolism-mediated toxicologic mechanism could form the basis for idiosyncratic liver injury in patients receiving EN therapy. PMID- 1449536 TI - Modulation of deoxycytidylate deaminase in intact human leukemia cells. Action of 2',2'-difluorodeoxycytidine. AB - Cellular metabolism studies had demonstrated previously that low cellular concentrations of 2',2'-difluorodeoxycytidine (dFdC) nucleotides are eliminated by deoxycytidylate deaminase (dCMPD), whereas dCMPD activity is inhibited at high cellular dFdC nucleotide levels (Heinemann et al., Cancer Res 52: 533-539, 1992). An assay for measuring dCMPD activity in intact human leukemia cells has now been developed to permit investigations of the interactions of dFdC nucleotides with dCMPD in intact cells in which the regulated nature of this enzyme was not disrupted. Using [14C]dCyd as the substrate, radioactivity that accumulated in dTTP was quantitated after high-pressure liquid chromotography by a radioactive flow detector. The assay was first characterized using either the dCMPD inhibitor tetrahydrodeoxyuridine (H4dUrd) which directly inhibits dCMPD, or thymidine and 5 fluoro-2'-deoxyuridine (FdUrd) which indirectly inhibit and activate dCMPD, respectively, by affecting the cellular dCTP:dTTP value. Measured by this in situ assay, there was a strong correlation between dCMPD activity and dCTP:dTTP levels. Consistent with previous studies using partially purified enzyme, incubation of cells with dFdC resulted in a concentration-dependent inhibition of dCMPD in situ. The mechanism of modulation of dCMPD by dFdC, however, was clearly different from that of thymidine and FdUrd. In addition to the effect of dFdC on cellular dCTP:dTTP, our findings also suggested an additional inhibitory mechanism, possibly a direct interaction between dCMPD and dFdC 5'-triphosphate. Thus, results obtained using this direct assay of dCMPD in intact cells support the hypothesis that dCMPD is inhibited by nucleotides of dFdC. PMID- 1449537 TI - Rat liver metabolism and toxicity of 2,2,2-trifluoroethanol. AB - 2,2,2-Trifluoroethanol (TFE) is a metabolite of anesthetic agents and chlorofluorocarbon alternatives. Its toxicity in rats is a consequence of its metabolism to 2,2,2-trifluoroacetaldehyde (TFAld) and then to trifluoroacetic acid (TFAA). The enzymes involved in the toxic metabolic pathway have been investigated in this study. For the reaction of TFE to TFAld, the major hepatic metabolism associated with toxicity (as assessed by pyrazole-inhibitability) was NADPH dependent and occurred in the microsomes, whereas for TFAld conversion to TFAA, NADPH-dependent microsomal metabolism was significant, but mitochondrial and cytosolic metabolism in the presence of NADPH were also major contributors. NADPH-dependent hepatic microsomal metabolism of TFE to TFAld and TFAld to TFAA was inhibited by carbon monoxide, 2-allyl-2-isopropylacetamide, SKF-525A, metyrapone, imidazole, and pyrazole, and both reactions were oxygen dependent. The metabolism of TFE to TFAld was inhibited by diethyldithiocarbamate, a specific inhibitor of cytochrome P450E1, and by a monoclonal antibody to P4502E1, whereas the metabolism of TFAld was inhibited by neither. Ethanol pretreatment of rats enhanced the Vmax for hepatic microsomal metabolism of TFE to TFAld from 5.3 to 9.7 nmol/mg protein/min, while for TFAld to TFAA the Vmax was increased from 4.3 to 6.5 and the Km was unaffected for both reactions. Phenobarbital pretreatment of the rats did not affect any of these kinetic parameters. Coadministration of ethanol and a lethal dose of TFE very markedly decreased the lethality. Both the lethality (LD50 0.21 to 0.44 g/kg) and the metabolic kinetic parameters [(Vmax/Km)H(Vmax/Km)D = 4.2] were affected markedly when deuterated TFE replaced TFE. In contrast, deuteration of TFAld did not affect its lethality or rates of metabolism, but did affect its Km. Taken together these results indicate that P4502E1 catalyzed toxicity-associated hepatic metabolism of TFE to TFAld, while TFAld metabolism was catalyzed by a P450 which was not P4502E1. The hepatic metabolism of TFAld was not associated with its toxicity, which has been determined previously to be associated with its intestinal metabolism. PMID- 1449538 TI - Demonstration of similar calcium dependencies by mammalian high and low molecular mass phospholipase A2. AB - The in vitro Ca2+ dependencies of arachidonyl (AA)-selective high molecular mass phospholipase A2 (HMM, 85 kDa-PLA2) and human low molecular mass (LMM-Type II, 14 kDa)-PLA2 were compared. When the LMM-PLA2 and HMM-PLA2 enzymes were examined for hydrolysis against [3H]AA Escherichia coli in an ethyleneglycol-bis(beta aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA)-free buffer system, neither enzyme demonstrated activity below 10 microM free Ca2+. Beyond 11 microM Ca2+ both enzyme activities increased steadily exhibiting 50% of maximal activity at 0.1 and 1.0 mM, respectively. Using EGTA-regulated free Ca2+ buffers, both enzymes responded in a biphasic manner, achieving 50% of the maximum response by 0.5 microM Ca2+, stabilizing up to 0.1 mM, then further increasing with exposure to millimolar Ca2+ concentrations. Replacement of [3H]AA-labeled phosphatidylethanolamine vesicles for [3H]AA E. coli or using Tris-HCl buffer instead of HEPES buffer did not alter these findings significantly. The presence of EGTA had a pronounced concentration-dependent effect on the activity of both the HMM- and LMM-PLA2 enzymes but only in the range of 0 to 100 microM free Ca2+. EGTA (EC50 approximately 200 microM) reduced the concentration of Ca2+ required by PLA2 to achieve 50% of maximal acylhydrolysis. In contrast, the Type I bovine pancreatic PLA2 required millimolar Ca2+ concentrations to elicit 50% of the maximal response in both EGTA-free or EGTA-containing systems, which is concordant with its extracellular role as a digestive enzyme. These data suggest that the LMM-Type II PLA2 and HMM-PLA2 are both activated at submicromolar, intracellularly relevant, Ca2+ concentrations and therefore have the ability to contribute to cellular lipid metabolism. PMID- 1449539 TI - The effect of malaria infection on 3'-azido-3'-deoxythymidine and paracetamol glucuronidation in rat liver microsomes. AB - The effect of malaria infection on UDP-glucuronosyltransferase (UDPGT) activity was investigated in rat liver microsomes using 3'-azido-3'-deoxythymidine and paracetamol. The Michaelis-Menten parameters, Km and Vmax were calculated and intrinsic clearance values were estimated for normal and infected livers. The results show that malaria infection alters the activity of UDPGT. PMID- 1449540 TI - Actin cytoskeleton, tubular sodium and the renal synthesis of dopamine. AB - The present study has examined the effect of colchicine and cytochalasin B, two cytoskeleton disrupter compounds, on the formation of dopamine in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) was also examined. The accumulation of newly formed dopamine and DOPAC in kidney slices loaded with L-DOPA (10-100 microM) was found to be dependent on the concentration of L-DOPA, being similar in control conditions and in preparations treated with increasing concentrations of colchicine (5, 10 and 50 microM). By contrast, cytochalasin B (5, 10 and 50 microM) was found to produce a concentration-dependent reduction in the formation of dopamine and of its deaminated metabolite DOPAC in kidney slices loaded with L-DOPA (10-100 microM). The inhibitory effect of cytochalasin B on the formation of dopamine was found to be completely abolished in kidney slices pretreated with ouabain (500 microM) or when sodium concentration in the incubation was reduced from 120 to 20 mM. On its own, ouabain (500 microM) was found to reduce the formation of dopamine by 55%; the effect of reducing sodium concentration in the incubation medium to 20 mM was also a significant reduction (53% decrease) in the formation of dopamine. The accumulation of DOPAC did always parallel that of its parent amine. It is concluded that the renal formation of dopamine is dependent on the concentration of sodium in the medium and the integrity of the tubular transport of sodium, namely on the association between actin cytoskeleton and Na+,K(+)-ATPase, appears to be determinant. PMID- 1449541 TI - Fasting increases the sensitivity of hepatic harmol glucuronidation to hypoxia. AB - Livers from fasted (N = 16) and fed (N = 22) rats were perfused with harmol (50 microM) for an initial 30 min with normal oxygen delivery (6-10 mumol/min/g liver), then for 45 min with perfusate equilibrated with O2/N2 mixtures, which reduced hepatic oxygen delivery to 0.9-6 mumol/min/g liver, and finally for a further 30 min period of normal oxygenation. Seventy per cent of the harmol eliminated was accounted for as the glucuronide conjugate and approximately 5% as the sulphate conjugate. During the hypoxia phase with fed preparations, decreasing oxygenation did not reduce harmol clearance or harmol glucuronide formation clearance until oxygen delivery was less than 2.5 mumol/min/g liver, whereas with fasted preparations this hypoxic threshold was much higher (5 mumol/min/g liver). Below the hypoxic threshold, harmol clearance was linearly related to oxygen delivery in both groups. Hepatic tissue concentrations of unchanged harmol at the end of the hypoxia phase were double those after the same period of normal oxygenation, whereas tissue harmol glucuronide concentrations were similar. By establishing a hypoxic threshold for reduced oxygen availability this study shows that harmol glucuronidation is relatively insensitive to hypoxia, but sensitivity increases markedly in fasted animals. PMID- 1449542 TI - Comparative binding of etretinate and acitretin to plasma proteins and erythrocytes. AB - The interactions of etretinate and its main metabolite acitretin with human plasma proteins have been investigated in vitro by an erythrocyte partitioning technique that allows a quantitative estimation of the plasma and erythrocyte binding. Etretinate was extensively lipoprotein-bound (75% of plasma etretinate), with a binding constant for its main low density lipoprotein carrier of 40 x 10(6) M-1, accounting for 48% of the total plasma-bound drug. Acitretin was mainly albumin-bound (91% of plasma acitretin), with a binding constant of 0.7 x 10(6) M-1. The total plasma binding of both drugs was > 99% and, in blood, the fractions associated with erythrocytes were 14.5 and 8.1% of the total amount for etretinate and acitretin, respectively. PMID- 1449543 TI - A gas chromatographic procedure for separation and quantitation of the enantiomers of the antidepressant tranylcypromine. AB - A novel assay procedure has been developed that allows for the separation and quantification of the enantiomers of the monoamine oxidase inhibitor tranylcypromine (TCP) in brain and liver of rats. The analytical method involves extraction of the drug from rat tissue with an organic solvent. TCP is then derivatized with S-(-)-N-(trifluoroacetyl)-prolyl chloride to allow gas chromatographic analysis of the resulting diastereoisomers. Conditions for analysis by a gas chromatograph equipped with a nitrogen-phosphorus detector and a capillary column are described. The method has been applied to the separation and quantification of the enantiomers of TCP in samples of brain and liver of rats that had been injected with this drug alone and after pretreatment with iprindole, a drug known to block aromatic ring hydroxylation. PMID- 1449544 TI - Differential stereospecificities and affinities of folate receptor isoforms for folate compounds and antifolates. AB - Two membrane folate receptor (MFR) isoforms are present in human tissues i.e. MFR 1 (e.g. placenta) and MFR-2 (e.g. placenta, KB cells, CaCo-2 cells). MFR-1 was expressed in COS-1 cells and the resulting protein had the same polypeptide molecular weight as the native protein. The affinities of (6S) and (6R) diastereoisomers of N5-methyltetrahydrofolate, N5-formyltetrahydrofolate, and 5,10-dideazatetrahydrofolate as well as folic acid and methotrexate to MFR-1, MFR 2 and placental MFR (MFR-1 plus MFR-2) were determined in terms of the Ki values for their competitive inhibition of the binding of [3H]folic acid to these proteins. The results indicated a striking difference in the stereospecificity of MFR-1 and MFR-2 for reduced folate coenzymes; MFR-2 preferentially bound to the physiological (6S) diastereoisomers and MFR-1 bound preferentially to the unphysiological (6R) diastereoisomers, while dideazatetrahydrofolate did not show significant stereospecificity for MFR-1. Furthermore, MFR-2 displayed significantly (2- to 100-fold) greater affinities for all the compounds tested compared to MFR-1. Purified placental MFR, a natural source of MFR-1 which contains variable amounts of MFR-2, showed intermediate Ki values for the compounds tested compared with MFR-1 and MFR-2 and stereospecificities similar to MFR-1. These observations demonstrate striking differences in the ligand binding sites of MFR-1 and MFR-2 which could potentially be exploited in the design of MFR isoform specific antifolates. PMID- 1449545 TI - The effect of pubertal delay on adult height in men with isolated hypogonadotropic hypogonadism. AB - To determine whether delay of puberty alters adult height, we retrospectively evaluated the adult height of 41 patients who met rigorous criteria for the diagnosis of isolated hypogonadotropic hypogonadism. The adult height of these patients was compared with the mean height of normal American men at age 18 in the 1979 National Center for Health Statistics survey and with the mean adult height of 50 male normal volunteers who had been studied on the same wards as the patients with hypogonadotropic hypogonadism. The mean adult height of the men with isolated hypogonadotropic hypogonadism was 179.7 cm, which exceeded the height of the 50 control subjects and the normal American men (both 176.8 cm) by 2.9 cm (P less than 0.05 and P less than 0.006, respectively). The mean age at treatment to induce puberty was 20.0 yr, which corresponded to a mean delay in the onset of puberty of more than 8 yr relative to normal males. The final height of the men with hypogonadotropic hypogonadism correlated significantly with the duration of pubertal delay (r = 0.32, P = 0.04). Most of the enhanced mean adult height of the patients with isolated hypogonadotropic hypogonadism was attributable to those patients in whom treatment to induce puberty had been delayed to age 18 or greater. The mean adult height of these patients was 182.4 cm, or 5.6 cm greater than the mean height of the 50 controls or of normal American men (P less than 0.001). The mean adult height of patients whose treatment began between 10 and 17 yr of age was 175.0 cm, which did not differ significantly from that of normal men. We conclude that prolonged delay of puberty (6 or more yr) in men with isolated hypogonadotropic hypogonadism is associated with a modest increase (approximately 5 cm) of adult height. PMID- 1449546 TI - The man did fine, but what about the wahoo? PMID- 1449547 TI - More on Gallo and Popovic. PMID- 1449548 TI - Goya's living skeleton. PMID- 1449549 TI - My last will and testament on rapid elimination and ultimate global eradication of poliomyelitis and measles. PMID- 1449550 TI - Evidence of stress throughout the profession. PMID- 1449551 TI - Why does Australia have no national drug policy? PMID- 1449552 TI - Oestrogen replacement after oophorectomy: comparison of patches and implants. PMID- 1449553 TI - Structure-activity relationships in platelet-activating factor (PAF antagonists). 6. Synthesis and in vitro antagonistic activities of 2-substituted 5 oxotetrahydrofurans. AB - The synthesis of 2,5-disubstituted tetrahedrofuran compounds as potential in vitro PAF antagonists is described. Results demonstrate that the structural requirements for potent PAF antagonist activity are: a moderate lipophilic group or a trimethoxyphenyl group in position-5, and a long aliphatic chain terminated by a cationic polar head in position-2. The cis-trans configuration does not induce any difference in biological activity. Some conformational features of the putative PAF receptor are proposed in light of the present findings. PMID- 1449554 TI - A perinatal ethics committee on abortion: process and outcome in thirty-one cases. PMID- 1449555 TI - [Effects of captopril on microcirculation and tissue oxygen balance in patients with hypertension]. AB - Bulbar conjunctival microcirculation, aggregation of platelets and red blood cells, skin oxygen balance were studied in 22 patients with Stage II hypertensive disease. Captopril was found to decrease not only blood pressure, but aggregation of platelets and red blood cells and to improve tissue oxygen supply. With inadequate doses of the drug, an extreme lowering in blood pressure resulted in deteriorated skin oxygen supply along with unaltered aggregation of cellular elements. PMID- 1449556 TI - Proceedings of a consensus development conference on standardized measures in diabetic neuropathy. Autonomic nervous system testing. PMID- 1449557 TI - Ethanol-induced disturbances of gliogenesis and neuronogenesis in the developing murine brain: an in vitro and in vivo immunohistochemical and ultrastructural study. AB - The effects of ethanol on murine brain development were studied in a model of whole embryo culture and in vivo. Ethanol locally enhances cell death in the primitive neuroepithelium. During neuronal migration, ethanol induces a premature transformation of the radial glial guides into astrocytes. Ethanol also inhibits the late gliogenesis. The resulting postmigratory neocortex displays an abnormal neuronal pattern almost completely deprived of vertical columnization. These glial-neuronal disturbances can explain neuropathological and clinical features of the fetal alcohol syndrome. Our study provides also an experimental tool for the study of cell death in normal and abnormal conditions at early stages of neurogenesis. PMID- 1449558 TI - The effect of chronic ethanol consumption on NADH- and NADPH-dependent generation of reactive oxygen intermediates by isolated rat liver nuclei. AB - Previous results have shown that microsomes from ethanol-treated rats generate reactive oxygen intermediates at elevated rates as compared to pair-fed controls in the presence of NADH and especially NADPH. Since isolated rat liver nuclei can produce oxygen radicals with NADH or NADPH as reductants, the effect of chronic ethanol treatment on nuclear generation of reactive oxygen intermediates was determined. Ethanol treatment increased the activity of NADH (+27%) and NADPH (+50%) cytochrome c reductase in the nucleus. Nuclear lipid peroxidation, H2O2 production, and generation of hydroxyl radical-like species were increased by about 25 to 40% after ethanol treatment. In contrast to microsomes, where NADPH dependent rates were higher than the NADH-dependent rates, in nuclei, NADH was as effective as, or even more reactive than NADPH in promoting production of various oxidizing species. The increases in oxygen radical production by nuclei after ethanol treatment were less than the increases found previously for microsomes. Moreover, rates of oxygen radical production by nuclei were less than 10% of the corresponding rates found with microsomes, suggesting that it is unlikely that the small increases found with nuclei after ethanol treatment contribute significantly towards the development of a state of oxidative stress in the liver. PMID- 1449559 TI - The acute effects of ethanol and acetaldehyde on rates of protein synthesis in type I and type II fibre-rich skeletal muscles of the rat. AB - Young rats were injected with either ethanol (75 mmol/kg), acetaldehyde (2.8 mmol/kg) or isovolumetric amounts of NaCl (0.15 mol/l, i.e. controls) with or without inhibitors of alcohol dehydrogenase (4-methylpyrazole) or aldehyde dehydrogenase (cyanamide). After 2.5 hr, fractional rates of protein synthesis (i.e. ks) in the soleus (Type I fibre-rich) and plantaris (Type II fibre-rich) muscles were measured. Ethanol alone reduced ks in both soleus and plantaris muscles, by approx. 25%. Pretreatment of ethanol-dosed rats with 4-methylpyrazole raised plasma ethanol levels and reduced ks in the soleus and plantaris by approx. 35%. Pretreatment of ethanol-dosed rats with cyanamide also increased plasma ethanol and further potentiated the effects of ethanol by reducing ks in the soleus and plantaris by approx. 65%. Acetaldehyde alone reduced ks by approx. 15%, and this effect was not significantly altered by 4-methylpyrazole pretreatment. In some instances, the plantaris was slightly more sensitive to ethanol and acetaldehyde than the soleus. Similar conclusions were derived when data were expressed relative to either RNA or DNA. The data thus suggest that the ethanol-induced inhibition of skeletal muscle protein synthesis may possibly be independently mediated by both ethanol and acetaldehyde. PMID- 1449560 TI - Glucose 1,6-bisphosphate and fructose 2,6-bisphosphate in muscle from healthy humans and chronic alcoholic patients. AB - Chronic alcohol intake produces an increase in the concentration of glucose 1,6 bisphosphate and fructose 2,6-bisphosphate in human muscle before the first sign of myopathy appears. When myopathy was present both sugars decreased to the levels of healthy humans. These changes could contribute to the decline in skeletal muscle performance. PMID- 1449561 TI - Influence of dietary n-6/n-3 polyunsaturated fatty acid balance on the development of tolerance during chronic ethanol intoxication in rats. AB - The present study addresses the possible interacting effects of dietary n-6/n-3 polyunsaturated fatty acid (PUFA) balance and chronic ethanol intoxication on the synaptic membrane responses to ethanol and the development of tolerance in rats. Wistar rats were fed either a standard lab chow or various semi-synthetic diets: rich in PUFA (from soya oil: SO), deficient in linolenate (from sunflower oil: SFO) or rich in long-chain (n-3) PUFA (cod liver oil: CLO). Male adult rats from the second specially fed generation were submitted to a 3-week alcoholization by daily intubation. Functional tolerance was quantified by the hypothermic response to a challenge dose of ethanol. Synaptic fluidity and sensitivity to ethanol (variations after acute ethanol addition) were assessed by fluorescence polarization (FP) of DPH, TMA-DPH or PROP-DPH. Membrane fatty acid composition was determined by GLC. The fatty acid composition of the synaptic membranes was influenced by the diet, but rearrangements among the lipids occurred, resulting in an apparent stability in brain membrane fluidity parameters. Nevertheless, clear-cut differences were noted in response to ethanol intoxication according to the diet. In the same period of time, rats fed SFO or CLO diets were unable to develop tolerance to ethanol at the membrane level as well as functionally, contrarily to the rats fed SO or standard diets. The structurally specific roles of PUFA are suggested by the negative membrane effects of the alpha-linolenate deficient diet (SFO) and the positive ones of a diet (SO) rich and well balanced in (n-3 + n-6) PUFA. Furthermore, the n-6/n-3 PUFA balance in the synaptic membrane needs to be kept within very narrow limits to allow normal development of the adaptive response to ethanol. PMID- 1449562 TI - Time-dependent effect of the angiotensin converting enzyme inhibitor, abutapril, on voluntary alcohol intake in the rat. AB - The angiotensin converting enzyme (ACE) inhibitor, abutapril (CGS 16617), was administered daily for 3 weeks to six different groups of rats at intervals of 15, 30, 45, 60, 90 or 120 min prior to a 40-min daily access to alcohol. Compared to a control group receiving the saline vehicle, abutapril (20 mg/kg) produced a significant and progressively increasing reduction in alcohol intake over the 3 week period of administration. In addition, intervals around the 60-min mark appeared to produce a more pronounced effect on alcohol intake such that a U shaped function of interval emerged. These findings indicate that the interval between abutapril administration and alcohol consumption is an important variable in determining the ability of abutapril to reduce alcohol intake. Treatment of human alcohol misuse with ACE inhibitors might be more successful if done on a symptomatic basis. PMID- 1449563 TI - Triptosine, an L-5-hydroxytryptophan derivative, reduces alcohol consumption in alcohol-preferring rats. AB - Triptosine is a new L-5-hydroxytryptophan derivative whose effect has been studied in the Long-Evans alcohol-preferring rat. At an oral dose of 100 mg/kg once daily, triptosine reduced alcohol consumption by 42% in the second week of treatment and increased that of water by 80%. The results suggest that this precursor of serotonin might play an important role in diminishing preference for alcohol and reaccustoming the animal to water, without exerting an anorexic effect. PMID- 1449564 TI - Plasma atrial natriuretic factor during ethanol ingestion in volume-loaded subjects. AB - The present study was designed to test whether ethanol ingestion affects plasma atrial natriuretic factor (ANF) concentration in healthy volunteers. On the basis of previous studies showing that ethanol induces a diuretic response and a decrease in atrial size (atrial distension), it was hypothesized that ethanol intake might be associated with a decrease in plasma ANF level. To somewhat increase plasma ANF level, the subjects were slightly loaded with water before the trial. As compared with juice, ethanol, 1 g/kg within 1 hr, increased urine output [405 +/- 37 (mean +/- SEM) ml/hr vs. 197 +/- 20 ml/hr, P less than 0.001]. Left atrial size decreased similarly (P less than 0.001) with both drinks. Plasma ANF concentration did not change with either ethanol or juice during the 3-hr study period. No changes were observed in plasma arginine vasopressin concentration and plasma renin activity. Our results are in conflict with previous reports in fasted subjects showing significant changes in plasma concentrations of the same hormones. Thus, the basal fluid balance seems to be crucial to the hormonal response to ethanol. The plasma concentrations of the hormones measured in this study do not directly explain the diuretic response to ethanol observed in slightly volume-loaded subjects. PMID- 1449565 TI - Acculturation and drinking patterns among U.S. Anglos, blacks, and Mexican Americans. AB - The relationship between acculturation, generational status/nativity and drinking patterns is examined using data from a 1988 community survey of 1286 adult regular drinkers (at least two drinks/month) in San Antonio, Texas. This sample includes 412 Anglo, 239 Black, and 635 Mexican American respondents, with Mexican Americans further classified into high, medium, and low acculturation groups using a language-use-based acculturation measure. This data set allows comparisons between racial/ethnic majority and minority groups with further comparisons between Black and Mexican American subgroups. These racial/ethnic and acculturation level comparisons highlight the effects of minority status and cultural differences between groups with regard to drinking patterns. Overall, the analyses indicate little evidence to support an 'acculturation stress' model of alcohol use, wherein the stresses of acculturation produce higher levels of alcohol consumption among moderately or higher acculturation groups. Generally, in our data, quantity and frequency consumption was somewhat higher among the least acculturated males and moderately acculturated females. Further analyses by generational status indicate heavier consumption patterns among second-generation individuals, especially among the less acculturated, though those differences were eliminated by controls. The findings highlight inadequacies of using generational status/nativity measures alone to assess acculturation level. Further, joint effects of acculturation level and generational status suggest the viability of a cultural marginality model of acculturation, though many of the effects of acculturation and generational status are explained by demographic and psychosocial factors. PMID- 1449566 TI - A method for maintaining constant ethanol concentrations in cell culture media. AB - The present study reports on the development of a model for maintaining constant ethanol concentrations over time in cell culture media. When neuroblastoma x glioma cells (NG 108-15) were grown in ethanol containing media under standard cultivation conditions in the incubator at 37 degrees C, a 90% evaporation was observed after 24 hr. To counteract evaporation, the cell culture dishes were placed inside polystyrene boxes together with an open dish containing an appropriate amount of ethanol. By using such procedure, the decrease in ethanol concentration in the culture media was completely avoided. Cultivating cells in ethanol-free media inside sealed plastic boxes did not change their viability, growth rate, protein and phospholipid composition of the cells or the pH of the media, compared to cultures grown outside the boxes. PMID- 1449567 TI - [Management of fever in children: study and practice in a center for family medicine]. AB - For three consecutive weeks a questionnaire was administered to 149 parents that took children under age 13 to Dr. Pila Hospital Family Practice Center. Information was obtained about their understanding of fever and its management. In our study we found parents who had no knowledge about what temperature is considered fever. As a result, there may be children who have been unnecessarily treated for temperatures that are normal. Others failed to recognize high fever and delayed treatment. The findings of this study are consistent with the idea that, in general, there is little knowledge about the definition of fever and its treatment, which suggests the need of an educational program. PMID- 1449568 TI - [Effectiveness of short-term corticosteroid therapy in patients with acute bronchial asthma in Puerto Rico]. AB - This is a pilot study realized in the San Juan City Hospital Pediatric Emergency Room to determine the efficacy of the short-term use of corticosteroids in pediatric patients (5 to 6 years old) with the diagnosis of acute bronchial asthma during the months of March to June 1992. Twenty three (23) cases were evaluated, of which, 8 cases were excluded because they did not comply with the eligibility criterias. The treatment was implemented in a random fashion, which consisted of one control group of treatment with different corticosteroids in combination with albuterol. The patients were evaluated at 0, 2, 6, 12 and 24 hr of therapy a pulmonary index, peak expiratory flow rate (PEFR) and pulse oximeter saturation. On admission to the study the average pulmonary index was 6 and PEFR of less than -3sd. When the patients achieved a pulmonary index of < 4, PEFR > 70% and pulse oxygen saturation of > 95% they were discharged. They were reevaluated at 5 to 7 days and 10 to 14 days after discharge. Using the same objective parameters patients that used corticosteroids had a tendency to improve or maintain the pulmonary index, PEFR and oxygen saturation between normal values. In this study it was possible to identify a tendency in the patients who used corticosteroids: the hospitalizations and exacerbations were less. The extension of the study in terms of population sample offers a better statistical representation to determine the real tendency or conclusions. PMID- 1449570 TI - Attitudes and knowledge toward bicycle helmet by school age children. AB - Approximately 600 children under the age of 15 years, die each year in bicycle related accidents. Over 80% of these deaths involve trauma to the head. Almost one fourth of all significant brain injuries in children are bicycle related. In spite of these significant statistics, bicycle helmet use in Puerto Rico has not received the necessary publicity to increase their use. Pediatricians should encourage helmet use and counsel parents about the important of this device. A case control study of accidents among bicycle riders experiencing a crash demonstrates that safety helmets reduce the risk of head injury by 85% and brain injury by 88%. The recommendation of current safety counseling practices should be incorporated as part of the routine pediatrician visit. Educational campaigns targeted at parents and children focusing on the incidence of consequences of bicycle crashes should be the primary goal for all primary practitioners, since the effectiveness of helmets in preventing head injuries might substantially increase helmet ownership among children. To assess the prevalence of bicycle helmet ownership and the associated factors with this, we surveyed 146 school age children evaluated at the Pediatrics Clinics of the University Hospital Dr. Ramon Ruiz Arnau from January to March 1991. We concluded that only 7.5% of our sample use the helmets. PMID- 1449569 TI - [Prevalence of obesity and associated conditions in a center for family medicine]. AB - Obesity is the most prevalent nutritional problem in North America and is associated with multiple chronic diseases. A sample, stratified by age and sex (N = 193), was taken from all the patients that visited Dr. Pila Hospital's Family Practice Center during a two month period. From the medical records, data was obtained about age, sex, body mass index, and the presence of diabetes mellitus, arterial hypertension, hypercholesterolemia or hyperlipidemia. The mean age was 44.8 years. The prevalence rates for obesity, hyperlipidemia, arterial hypertension, and diabetes were 53.4%, 69.5%, 26.0% and 17.2% respectively. The prevalence rates for hypertension and diabetes were twice in obese subjects than in non obese subjects. No statistical association was found between obesity and hyperlipidemia. Although this sample is not representative of the general population, this study sheds light on the impact of obesity and associated conditions among users of health services. PMID- 1449571 TI - [Evaluation of infants born to mothers with a history of cocaine use during pregnancy]. PMID- 1449572 TI - Computers, diagnoses and patients with acute abdominal pain. PMID- 1449573 TI - Audit of computer-aided diagnosis of abdominal pain in accident and emergency departments. PMID- 1449574 TI - Conjunctival oxygen monitoring in the initial assessment of trauma. AB - The purpose of this study was to evaluate the use of the conjunctival oxygen tension (PCJO2) monitor during the early assessment of injured patients in the A&E Department of a large District General Hospital. The conjunctival oxygen sensor provides a non-invasive continuous monitor of tissue oxygenation in the palpebral conjunctiva and has been shown to detect early hypovolaemia in animal and human studies. For this preliminary report PCJO2 was recorded with initial clinical findings, standard cardiorespiratory parameters (pulse rate, blood pressure, respiratory rate, Glasgow Coma Score) and final diagnosis. Low PCJO2 (less than 45 mmHg) was associated with hypovolaemia, reduced cardiac output and chest injury. Normal PCJO2 in patients with severe head injury requiring transfer to the Regional Neurosurgical Centre or patients from multivictim road traffic accidents (RTAs) indicated no early occult cardiorespiratory compromise and this was subsequently confirmed. Monitoring PCJO2 seems to provide a valuable adjunct in the initial assessment of the injured patient. PMID- 1449575 TI - An ambulance helicopter for emergency calls. AB - The use of a helicopter as a primary response vehicle for the Cornwall Ambulance Service is presented. A brief analysis of the activities of the First Air Ambulance is described and an appraisal of its effects on the overall performance of the Service is given. Emphasis is given to patient acceptability and also to the flexibility of the helicopter in terms of its response to different situations. In conclusion, The Air Ambulance, as part of an integrated ambulance service, is an effective provider of good pre-hospital care. PMID- 1449576 TI - Can out-of-hours operating in gynaecology be reduced? AB - Against a background of concerns about future hospital medical staffing and the safety of unsupervised operations at night, this study examines which gynaecological operations now undertaken at night may be safely postponed until the following day. In the first phase of the study, the operations taking place at night in four hospitals were identified. In the second phase a nominal group technique was used to seek the extent of agreement among professionals about the appropriateness of postponing surgery to the following day in certain circumstances. There were considerable variations between hospitals in the volume of work and the grade of staff involved. The panel concluded that most operations now performed at night should not be postponed. This study suggests that there is limited scope for postponing gynaecological operations currently undertaken at night. PMID- 1449577 TI - A review of in-patient hand infections. AB - A retrospective review is presented of 64 patients with infections of the hand requiring admission to hospital. We present an account of the different types of hand infection encountered, together with details of the various aetiologies and microbiological findings where these are available. The management of hand infections is discussed with reference to the patients in our series, and in terms of the general principles involved. PMID- 1449578 TI - Reducing children's fear when undergoing painful procedures. PMID- 1449579 TI - Avulsion fracture of the straight and reflected heads of rectus femoris. AB - We present a rare case of avulsion fracture of the reflected head of rectus femoris. This occurred in a 13-year-old male footballer. Diagnosis was made with pelvic radiology and treatment was bed rest and analgesia. PMID- 1449580 TI - The management of quinine-induced blindness. AB - Given the potential toxicity of even a small number of quinine tablets we suggest that patients to whom these are prescribed should be alerted to this risk both by the prescribing clinician and by a warning, clearly printed on the tablet container. There is no evidence that increased retinal arteriolar dilation is of any value in the management of patients with quinine induced blindness. Therefore the use of SGB for this condition must be questioned unless a controlled trial is performed which shows benefits. We recommend that the aim of treatment has to be reduction in the plasma level of quinine. The most efficient way of accomplishing this is by repeated oral activated charcoal. PMID- 1449581 TI - Bone infection and the limping child in the accident & emergency department: a diagnosis to be considered. AB - The child who presents to the A&E department with a limp must be taken seriously. It is of paramount importance to include in the list of causes the possibility of infection. The diagnosis and treatment of subacute osteomyelitis in children is discussed to highlight the necessity for immediate referral and inpatient management. PMID- 1449582 TI - Skin ulceration due to cement. AB - Despite legislation that requires manufacturers to inform the public about the dangers of contact with cement, severe ulceration from cement contact still occurs. We present a retrospective study of seven patients presenting to this department over a 2-year period. All were male and employed in the building trade, their injuries being sustained whilst at work. The injuries were to the lower limb, often multiple and required a median of seven visits before healing was complete. One required hospital admission and skin grafting. PMID- 1449583 TI - Violence in the accident and emergency department. PMID- 1449584 TI - Accident--an anachronism? PMID- 1449585 TI - Effects of the Gulf War on accident & emergency attendances. PMID- 1449586 TI - Teaching trauma management. PMID- 1449587 TI - Pulsed electromagnetic energy and pre-tibial lacerations. PMID- 1449588 TI - Massive haemothorax from central venous catheterization: a note of caution. PMID- 1449589 TI - Teaching of basic life support. PMID- 1449590 TI - Sialic acid-binding proteins: characterization, biological function and application. AB - The last decade has witnessed steadily growing support for the notion that the carbohydrate portion of glycoconjugates is not merely an inert structural addition to the protein or lipid backbone. Considerable attention has been given to the chemical composition of glycosidic residues in such heteropolymers. Sialic acids are frequently occurring components of oligosaccharide side chains in glycoconjugates of most higher animals and a few microorganisms. They appear to play an important role as ligands in glycobiological interactions. Mediation of a proposed protein-carbohydrate recognition will necessarily involve a binding protein with the respective specificity. Such proteins thus are able to serve as receptors for certain types of carbohydrate moieties like sialic acids in vivo. Various members of this class of proteins have already proven their value as analytical tools in studying expression and localization of defined sialoglycoconjugates. These proteins attract much attention due to both their functions in situ and their potential as laboratory tools in glycoconjugate research in areas like biochemistry or histology. We present a survey of the purification, characterization and application of this class of proteins to illustrate the status of knowledge and the current directions of research in this field. PMID- 1449591 TI - A simplified combination of DNA probe preparation and fluorescence in situ hybridization. AB - Fluorescence in situ hybridization (FISH) has found widespread applications in cytogenetics. So far the standard protocols for probe amplification (and simultaneous labeling) by PCR, nick translation and in situ hybridization involve different buffer systems leading to a number of time consuming washing steps even before hybridization. In this manuscript we show a fast technique of a close combination of DNA probe preparation and in situ hybridization (ISH). This method was applied to metaphase chromosomes from human lymphocytes fixed on slides. Two specific repetitive DNA probes, the pUC 1.77 DNA probe and the DYZ1 repetitive DNA fraction were used, amplified and labeled in different ways. Additional experiments with total genomic male human DNA as the DNA probe suggest that this method may be extended to a large variety of other probes. Moreover the ISH technique described does not require toxic denaturing agents, such as formamide. PMID- 1449592 TI - Red blood cell partitioning of the [6S]- and the [6R]-isomer of N5 formyltetrahydrofolic acid. AB - The in vitro interaction of the [6S]- and [6R]-stereoisomers of CHO-THFA with human RBCs was investigated in the (therapeutically comparable) concentration range from 1.0 to 12.5 micrograms/ml. Both compounds are bound to RBCs with a kRBC ranging from 0.13 to 0.75 for [6S]-CHO-THFA and from 0.06 to 0.33 for [6R] CHO-THFA, respectively. The interaction of the [6S]-form with RBCs is about two times higher than of the [6R]-form. Incubation of CHO-THFA with RBCs over 24 h showed an accelerated disappearance from the test solution for [6R]-CHO-THFA with a mean t1/2 of 49.9 h in compare to t1/2 = 58.2 h for the [6S]-enantiomer. The results indicate that RBCs may play a major role for the pharmacokinetics and metabolism of CHO-THFA and may act as an intravasal depot especially for [6S]-CHO THFA. PMID- 1449593 TI - Effect of cinnamic and acrylic acids' derivatives on luminol-enhanced chemiluminescence of neutrophils. AB - Fourteen derivatives of cinnamic and acrylic acids were evaluated for their ability to modulate chemiluminescence, evoked by neutrophils that had been exposed to luminol and phorbol-myristate-acetate. Compounds with one or two hydroxyl groups on the phenyl ring demonstrated significant inhibition of the chemiluminescence, but this inhibition was diminished by methoxylation. Saturation of the double bond in the aliphatic chain of cinnamic acid at C6 enhanced the chemiluminescence to a small degree. All three acrylic acid derivatives demonstrated a marked inhibition of the luminol chemiluminescence, indicating that characteristics of the heterocyclic ring is of utmost importance in this activity. PMID- 1449594 TI - Electrostatic potential barrier in asymmetric planar lipopolysaccharide/phospholipid bilayers probed with the valinomycin-K+ complex. AB - Using the carrier-ion complex valinomycin-K+, current/voltage (I/U) characteristics were registered for planar asymmetric lipid bilayers composed on one side of a phospholipid mixture and on the other side of rough mutant lipopolysaccharide. This system resembles the lipid matrix of the outer membrane of Gram-negative bacteria. The evaluation of the current/voltage curves yielded a highly asymmetric electrical potential barrier. The total potential difference between the phospholipid and the lipopolysaccharide was -85 mV, a result which cannot be explained by contributions of Gouy-Chapman potentials alone. The possible contribution of dipole potentials and influences of headgroup effects are discussed. It is shown that the asymmetry of the I/U-characteristic results from the differences of the surface charge densities of the two monolayers but not from those of the states of order of their hydrocarbon chains. PMID- 1449595 TI - Micromorphometric evaluation of changes in symmetry of sarcoplasmic reticulum membranes induced by vanadate. AB - Electron micrographs of light sarcoplasmic vesicles fixed with glutaraldehyde and osmium tetroxide followed by contrasting with uranyl acetate and lead citrate have been evaluated by registering their membrane profiles with a microdensitometer. The asymmetric arrangement of the two layers of the vesicular membrane could be ascertained by demonstrating a ratio of 1.5 for the thickness of the outer versus the inner membrane layer which is in general agreement with the proposed protein structure of the calcium transport enzyme. Treatment of the vesicles with low concentrations of vanadate (0.1 mM) results in a significant lowering of the symmetry ratio by 20% by reducing mainly the thickness of the outer membrane leaflet. Removal of the membrane lipids by treating the vesicles with phospholipase A2 and bovine serum albumin diminishes the membrane surface by 50% resulting in a significant increase of both the membrane thickness and the asymmetry ratio by 30 and 12% respectively. The vanadate induced reduction of membrane asymmetry is accentuated after delipidation indicating that the membrane lipids are not essential for the asymmetric appearance of the native membrane. The stability of the spherical form of the vesicles to delipidation implies that the transport molecules are conically shaped allowing strong mutual interactions. At a measured height of the molecule of 80 A in the membrane, the vanadate induced change in symmetry would be brought about by compensatory changes of less than 3 A of the outer (35 A) and the inner (25 A) diameter of the cone. PMID- 1449597 TI - Correlation of the conformation of a modified ribonuclease octapeptide, homologous to peptide T, with its ability to induce CD4-dependent monocyte chemotaxis. AB - Peptide T, from the human immunodeficiency virus (HIV), whose sequence is Ala-Ser Thr-Thr-Thr-Asn-Tyr-Thr, has been shown to inhibit attachment of this virus to T cells and neural cells bearing the CD4 receptor. This peptide shares extensive homology with the 19-26 segment of ribonuclease A (RNase A), whose sequence is Ala-Ala-Ser-Ser-Ser-Asn-Tyr-Cys. Based on comparison of the structures of peptides occurring in proteins of known structure that are homologous to peptide T, viz, RNase A and endothiapepsin and on conformational energy calculations, we predicted that peptide T adopts a structure much like that for residues 19-26 in RNase A. A critical feature is a bend involving residues Thr 4-Asn 7 in peptide T corresponding to Ser 22-Tyr 25 in the RNase A peptide. Our proposed structure for peptide T has recently been confirmed by Cotelle et al. (Biochem. Biophys. Res. Commun. 171, 596-602). We now show directly that the RNase A peptide, with Met replacing Cys 26 to prevent disulfide exchange reactions, strongly induces monocyte-chemotaxis that is blocked by anti-CD4 monoclonal antibody. Both peptide T and RNase A fail to induce chemotaxis, however, in neutrophils which do not express surface CD4 receptors. These results suggest that both peptides interact with the CD4 receptor in inducing monocyte chemotaxis. We have also prepared cyclo-RNase A peptide with Met 26. Using molecular dynamics and conformational energy calculations, we find that the cyclic peptide cannot form a bend structure involving Ser 22-Tyr 25 that is superimposable on the RNase A bend.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449596 TI - Heterologous expression and purification of active human phosphoribosylglycinamide formyltransferase as a single domain. AB - We report here for the first time that the GART domain of the human trifunctional enzyme possessing GARS, AIRS, and GART activities can be expressed independently in Escherichia coli at high levels as a stable protein with enzymatic characteristics comparable to those of native trifunctional protein. Human trifunctional enzyme is involved in de novo purine biosynthesis, and has long been recognized as a target for antineoplastic intervention. The GART domain was expressed in E. coli under the control of bacteriophage T7 promotor and isolated by a three-step chromatographic procedure. Two residues, Asp 951 and His 915, were shown to be catalytically crucial by site-directed mutagenesis and subsequent characterization of purified mutant proteins. The active monofunctional GART protein produced in E. coli can serve as a valuable substitute of trifunctional enzyme for structural and functional studies which have been until now hindered because of insufficient quantity, instability, and size of the trifunctional GART protein. PMID- 1449598 TI - The principal islet of the Coho salmon (Oncorhyncus kisutch) contains the BB isoenzyme of creatine kinase. AB - The importance of creatine kinase (E.C. 2.7.3.2) in endocrine tissues has been generally overlooked. Using a specific radiometric assay, we have demonstrated the existence of CK in the Brockmann body (principal islet) of the Coho salmon. We have purified this protein from insular tissue and concurrently purified CK from brain and muscle of the salmon. Purification characteristics, immunological cross-reactivity, and N-terminal sequence analysis have demonstrated that the predominant cytosolic CK from the Brockmann body is indistinguishable from the BB (brain) isoenzyme. Immunocytochemical studies indicated that the enzyme resides in the endocrine parenchyma. Phosphocreatine may serve as a reservoir of energy in the islet and augment its capacity to secrete hormones. The induction of CK-BB in the islet by other hormones could influence the secretion of insular hormones. Interorgan flux of the substrate creatine may be an undescribed mechanism of physiological regulation. PMID- 1449599 TI - Solution structure of a synthetic peptide corresponding to a receptor binding region of FSH (hFSH-beta 33-53). AB - The receptor binding surface of human follicle-stimulating hormone (hFSH) is mimicked by synthetic peptides corresponding to the hFSH-beta chain amino acid sequences 33-53 [Santa-Coloma, T. A., Dattatreyamurty, D., and Reichert, L. E., Jr. (1990), Biochemistry 29, 1194-1200], 81-95 [Santa-Coloma, T. A., Reichert, L. E., Jr. (1990), J. Biol. Chem. 265, 5037-5042], and the combined sequence (33-53) (81-95) [Santa-Coloma, T. A., Crabb, J. W., and Reichert, L. E., Jr. (1991), Mol. Cell. Endocrinol. 78, 197-204]. These peptides have been shown to inhibit binding of hFSH to its receptor. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy were used to determine the structure of the first peptide in this series, the 21 amino acid peptide hFSH-beta-(33-53), H2N YTRDLVYKDPARPKIQKTCTF-COOH. Analysis of CD data indicated the presence of approximately equal amounts of antiparallel beta-pleated sheet, turns including a beta-turn, "other" structures, and a small amount of alpha-helix. The major characteristics of the structure were found to be relatively stable at acidic pH and the predominant effect of increased solvent polarity was a small increase in alpha-helical content. One- and two-dimensional NMR techniques were used to obtain full proton and carbon signal assignments in aqueous solution at pH 3.1. Analysis of NMR results confirmed the presence of the structural features revealed by CD analysis and provided a detailed picture of the secondary structural elements and global folding pattern in hFSH-beta-(33-53). These features included an antiparallel beta-sheet (residues 38-51 and 46-48), turns within residues 41-46, and 50-52 (a beta-turn) and a small N-terminal helical region comprised of amino acids 34-36. One of the turns is facilitated by prolines 42 and 45. Proline-45 was constrained to the trans conformation, whereas proline-42 favored the trans conformer (approximately 70%) over the cis (approximately 30%). Two resonances were observed for the single alanine residue (A-43) sequentially proximal to P-42, but the rest of the structure was minimally affected by the isomerization at proline-42. The major population of molecules, containing trans-42 and trans-45 prolines, presented 120 NOEs. Distance geometry calculations with 140 distance constraints and energy minimization refinements were used to derive a moderately well-defined model of the peptide's structure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1449601 TI - The molybdoenzymes xanthine oxidase and aldehyde oxidase contain fast- and slow DTNB reacting sulphydryl groups. AB - The reactivities with an excess of 5-5'-dithiobis (2-nitrobenzoic) acid (DTNB) of sulphydryl residues present in xanthine oxidase and aldehyde oxidase were studied and compared. The results show that two classes of sulphydryl groups with quite different reactivities exist in both enzymes either native or denatured. Some of the available sulphydryl residues thus react instantaneously with the DTNB, whereas the others react very slowly following pseudo-first-order kinetics. The number of sulphydryl residues of each class and the rate constant of slowly reacting groups are, respectively, 1.7 and 0.8 in native xanthine oxidase and 1.6 and 1.7 in native aldehyde oxidase. In denatured enzymes, the number of fast- and slow-reacting sulphydryl residues obtained are, respectively, 13.9 and 7.9 in xanthine oxidase and 5.7 and 5.4 in aldehyde oxidase. Analogously, the rate constant for the slowly reacting groups is similar for the two native enzymes, but in denatured aldehyde oxidase it is double that of denatured xanthine oxidase. PMID- 1449600 TI - Temperature sensitivity of vinblastine-induced tubulin polymerization in the presence of microtubule-associated proteins. AB - The antitumor drug vinblastine has been a useful probe for examining the interaction of tubulin with the microtubule-associated proteins (MAPs), specifically with tau and MAP 2. Although tau and MAP 2 can stimulate microtubule assembly in vitro, their specific interactions with tubulin are known to differ. For example, in the presence of vinblastine, both tau and MAP 2 cause tubulin to form spirals, but tau causes formation of clustered spirals of high turbidity, while MAP 2 causes formation of loose spirals of low turbidity [Luduena et al., J. Biol. Chem. 259, 12890-12898 (1984)]. Although cold temperatures can inhibit microtubule assembly, cold has no effect on vinblastine-induced tubulin spiral formation. Consequently, we used the vinblastine-tubulin system to examine the interactions of tau and MAP 2 with tubulin at low temperatures. We found that tau tubulin-vinblastine complexes form about as well at 0 degree C as at 37 degrees C. In contrast, MAP 2-tubulin-vinblastine complexes form much less well at 0 degrees C than at 37 degrees C. We find, however, that MAP 2, at 0 degrees C, will strongly inhibit, and even reverse, formation of the tau-tubulin-vinblastine complex. This suggests that the temperature-sensitive factor is the MAP 2 stimulated tubulin-tubulin interaction rather than the MAP 2-tubulin interaction per se; this raises the possibility that the tubulin-tubulin interactions stimulated by tau differ in their temperature sensitivity from those stimulated by MAP 2. PMID- 1449602 TI - Primary structure of carboxypeptidase T: delineation of functionally relevant features in Zn-carboxypeptidase family. AB - The primary structure of carboxypeptidase T--a Zn-dependent extracellular enzyme of Thermoactinomyces vulgaris--was determined from the cloned cpT gene nucleotide sequence and compared to Zn-carboxypeptidases from various organisms. The compilation and analysis of multiple alignment accompanied by consideration of available tertiary structure data have shown that in the overall spatial structure and active site arrangement CpT is similar to other enzymes constituting the Zn-carboxypeptidase family. Nine of 16 amino acid residues found to be strictly invariant are presumably located close to the active site. The preservation of His69, Glu72, Asn144, Arg145, His196, Tyr248, and Glu270 identified previously as essential catalytic site participants implicates basically the same catalytic mechanism in the Zn-carboxypeptidase family. It is proposed that Pro205 and Asp256 should play an important role in proper S1' pocket spatial arrangement. The comparative analysis of amino acid variations in S1'-pocket enabled us to reveal structural determinants of the Zn carboxypeptidase primary specificity. The relatively reduced size of the pocket and negative charge of Asp253 are supposed to contribute correspondingly to A- and B-type substrate preferences of carboxypeptidase T endowed with dual primary specificity. PMID- 1449603 TI - Correlation between the compact regions predicted by the average distance map (ADM) and the biologically active sites in atrial natriuretic peptide. AB - The prediction of the short-range compact regions of human atrial natriuretic peptide (alpha-hANP), one of the biologically active peptides, has been made by means of the Average Distance Map(ADM). We found out that the location of the predicted short-range compact regions is consistent with the structural units determined by the NMR analysis (Kobayashi et al., 1988). Furthermore, the short range compact regions correspond well to the biologically active areas of atriopeptin (103-125)-amide (which is homologous peptide to alpha-hANP), detected by the glycine substitution technique (Konishi et al., 1987). The results suggest that a predicted short-range compact region can be regarded as a possible active site in a biologically active peptide. PMID- 1449604 TI - Molecular close-packing method and its application to crystal structure determination of deshexapeptide (B25-B30) insulin. AB - Based on the molecule-packing theory, we defined a molecule-packing function expressing the compatibility of packing among the symmetry-related molecules in a unit cell. A computer program imitating the close-packing of molecules in the objective crystal lattice and giving the function value of each rotation and translation of the molecule in the unit cell was performed, and it therefore made the close-packing of molecules express quantitatively. This method not only could judge a correct solution from several peaks of the rotation or translation function but it may also independently, quantitatively and quickly solve some specific problems of rotation and translation. Using known structure of despentapeptide (B26-B30) insulin as an example, the effectiveness of this method and its program was inspected, and this method was successfully applied to solving the translation problem of the unknown structure of deshexapeptide (B25 B30) insulin. The molecular close-packing method proved by the results of R search and electron density maps is relatively independent of the molecular replacement method, though an effective complement of it. PMID- 1449605 TI - A cDNA clone with anti-oncogene activity. AB - A cDNA clone, p14-6, which has an anti-oncogene activity on the v-Ki-Ras oncogene transformed malignant cell line DT, was found. This clone was recovered from the revertant R14 cells, which had been isolated by transfections of DT cells with a normal human fibroblast cDNA library cloned in pcD2, an Okayama-Berg vector. When transfected into DT cells, p14-6 clone gave rise to phenotypical flat reversion in 5-15% of DT transfectant colonies. The p14-6-transfected flat cell line, RR, was proven to be a true revertant with significantly reduced malignancy by in vitro and in vivo malignancy tests. All other clones recovered from R14 cells were unable to cause this reversion. Molecular hybridizations showed that the p14 6 was inserted into RR genome as tandem repeats, and no structural change was found in the v-Ki-Ras oncogene in RR genome. These facts suggest that the anti oncogene activity of the p14-6 clone on the DT cells may be exerted through expression of the cDNA contained in this clone. PMID- 1449606 TI - [Systematic modelling in nutrition]. AB - Live organisms can be considered as open complex systems in a steady state through which passes a flow of matter which undergoes a series of transformations which constitutes the nutritional process. The systemic approach and modelling procedure can be applied to nutrition as it can to other scientific areas, although examples of this particular application are few. This review describes the complexity of components in nutritional systems and presents a means of simplifying this. A section is given over to a comparative study of the main types of models (empirical vs mechanistic, static vs dynamic) which can be applied to nutrition. The other topics covered concern the modelling of the regulating systems in nutrition (homeostasis, homeorhesis), model validation and comments on application models and research. PMID- 1449607 TI - The influence of processing corn grain on glucose metabolism in ewes. AB - Glucose metabolism was studied in ewes fed 800 g chopped alfalfa hay (H) or 400 g alfalfa hay and 400 g corn grain given in whole (HWC), ground (HGC) or extruded (HEC) form. Daily intake of metabolisable energy and crude protein were: 5.8 MJ, 109 g; 9.0 MJ, 84 g; 9.5 MJ, 84 g and 8.5 MJ, 88 g in H, HWC, HGC and HEC, respectively. In situ ruminal degradability ranked whole, ground, and extruded corn in ascending order. Ruminal pH and concentration of acetic acid were lower and of propionic acid higher (P less than 0.05) in HEC than in HGC and HWC groups. Plasma level of glucose (P less than 0.10), insulin (P less than 0.05), and the ratio of insulin to non-esterified fatty acids (NEFA) (P less than 0.01) were higher in HEC than in other groups. Glucose irreversible loss (GILR) and entry rate (GER), recycling (GRec) and reentry (GRee) were determined by double isotope dilution procedure. GER, but not GILR, was higher in HWC than in H and HGC (6.98 mg/min/kg BW0.75 vs 3.97 and 4.24 mg/min/kg BW0.75, respectively; P less than 0.05) and than in HEC (4.84 mg/min/kg BW0.75; P less than 0.10). GRec and GRee were higher in HWC than in the other treatments. Grinding or extruding the grain increased ruminal degradability and decreased glucose entry rate. PMID- 1449608 TI - Pressure profile along the oesophagus during eructation in sheep. AB - The pressure profile along the oesophagus was recorded simultaneously with the flow rate of eructated gas in sheep to evaluate the oesophageal motor events leading to the relief of gas. All the eructation sequences started by a rise followed by a plateau of oesophageal pressure. The passage of gas at the tracheal level occurred during this plateau and not during the consecutive transient lowering of the oesophageal pressure. All eructation sequences ended by a peristaltic contraction of the oesophagus. The flow rate pattern of gas during eructation was affected by head position leading to different tensions of the oesophagus. We conclude that, despite the large volume of eructated gases, the eructation process is not significantly different in sheep compared to other animals. Therefore, by virtue of its unique physiological particularity, the sheep might be used as an experimental model for the evaluation of lower oesophageal sphincter (LOS) competence. PMID- 1449609 TI - Microstructure of skeletal muscles of growing calves fed silage-based vs hay based diets. II. Fibre type distribution. AB - As described in part I, samples of musculus longissimus dorsi, semimembranosus and semitendinosus were obtained post-slaughter from 2-week, 3-month and 10-month old bull calves. The 2-week-old calves were fed milk only. All the remaining animals were fed grass silage or hay ad lib and a restricted amount of concentrate from 2 weeks of age onwards. Muscle fibres were differentiated according to Ziegan (1979) into fast-twitch glycolytic, fast-twitch oxidoglycolytic and slow-twitch oxidative fibres (FTG, FTO and STO, respectively). The percent distribution of individual types of fibres was estimated as related to the calves age and diet. The most numerous were always fast-twitch glycolytic fibres, the lowest values being observed in the 2-week-old calves. The effect of the diet on fibre percentage distribution in 3-month-old calves differed from that found in 10-month-old animals. This research suggests that a hay-free diet based on grass silage alters the microstructure of skeletal muscles, which thus might also affect the quality of meat. PMID- 1449610 TI - [Effect of bean (Vicia faba) extrusion on nitrogen and starch intestinal flux in lactating cows]. AB - Four mature lactating Holstein cows fitted with permanent ruminal, duodenal and ileal cannulae were used to study the effect of extrusion at 195 degrees C of beans (Vicia faba cv Castel) on organic matter (OM), nitrogen (N) and starch degradation in the rumen and their flow to and absorption from the small intestine. The test protein sources, raw beans (RB) and extruded beans (EB), provided about 45% of the dietary protein. The diets were composed of 23.1% beans, 56.2% corn silage, 10.1% corn grain and 10.7% Italian rye-grass hay on a DM basis; the diets were isocaloric (4.5 Mcal/kg of DM) and isonitrogenous (14% of DM). Cr-EDTA, YbCl3 and purines were used as liquid, particulate and bacterial markers respectively. Extruding the beans did not influence intraruminal pH (6.6), ammonia-N (99 mg/l) and volatile fatty acids (97 mM/l) concentrations. Apparent digestibility in total tract of energy, OM, N and starch were not affected with inclusion of EB instead of RB, the corresponding mean values were: 66, 68, 64 and 95% of intake. Apparent ruminal digestion of OM, starch and N in the forestomach were 39, 58 and 52% for diets containing RB and 38, 72 and 45% for EB diets; efficiency of bacterial protein synthesis (gN/kg organic matter truly digested in the stomach) was higher for EN diets compared with RN diets (25 vs 22). Eating diets including EB increased non-ammonia-N, bacterial-N and dietary-N flows (g/d) to the duodenum compared with diets containing RB: 409 vs 366, 216 vs 194 and 193 vs 172 respectively; while starch flow was reduced (1.5 vs 2.2 kg/d) and OM flow was unchanged (9.8 kg/d). Apparent digestion from the small intestine (g/d) of nonammonia-N, bacterial-N and dietary-N were higher for EB diets: 268 vs 229, 181 vs 160 and 87 vs 69 respectively; meanwhile, starch digestion decreased (975 vs 1,612). The PDIA, PDIN and PDIE contents (g/kg of DM) of the RB were 33, 175 and 127 respectively; the corresponding values after extrusion were: 58, 147 and 178. PMID- 1449612 TI - Ontogeny of the liver nuclear T3-receptor during the last days of incubation and posthatch in the chick embryo. AB - The characteristics of the nuclear T3 receptor in the liver of the chick embryo were studied from incubation day 18 until day 1 posthatching. Treatment of the nuclei with 3 mol.l-1 MgCl2, which removed the endogenously bound hormone, was used in order to determine the total amount of receptors. The affinity constant Ka decreased between incubation day 18 (0.996 +/- 0.276.10(9) M-1) and day 19 (0.247 +/- 0.072.10(9) M-1), remained the same thereafter until hatching and increased again on day 1 posthatching (1.846 +/- 0.928.10(9) M-1). The total amount of receptors tended to increase from incubation day 18 to day 20 non pipping (np) (from 4.40 to 11.55 fmol/micrograms DNA) and decreased thereafter to 2.38 fmol/micrograms DNA on day 1 posthatching. The amount of free binding sites reached a maximum on day 19 (6.91 fmol/micrograms DNA) and then decreased drastically until posthatching (0.19 fmol/micrograms DNA). The maximal specific binding was found on day 20 (np), just prior to penetration of the air chamber. During the time at which the level of T3 remains high in the plasma, a reduction in the amount of receptor was observed, which may be the consequence of a down regulation by T3 itself. PMID- 1449611 TI - Purification of an ovine, androgen-dependent epididymal protein. Evidence for a strong amino acid sequence homology with serum albumin. AB - An ovine, testosterone-dependent protein was purified from an extract of epididymides of orchidectomized-, testosterone-implanted rams by ethylene glycol precipitation, anion exchange chromatography, preparative non-denaturing PAGE at alkaline pH and gel filtration. The protein which had previously been named ovine prealbumin-epididymis-specific protein (oPES), migrated as a single band ahead of ovine serum albumin (oSA). A single component, with an apparent MW of 60 kDa, lower than that of oSA, was also observed in SDS-PAGE. oPES was cleaved after lysyl residues using endoproteinase Lys-C and the hydrolysate was fractionated in 2 steps by reverse-phase HPLC. Six oligopeptides were recovered and sequenced. They all displayed complete identity with regions of bovine serum albumin scattered in the two-third N-terminal part. However, in 2 of them, there was no complete identity with homologous parts of oSA. This indicates that oPES and oSA are probably encoded by different genes. PMID- 1449613 TI - Oestrus and LH responses to oestradiol during lactational anoestrus in Chinese Meishan and large white sows. AB - To investigate endocrine mechanisms associated with the occasional occurrence of fertile oestrus during lactation in the high prolific Chinese Meishan (MS) breed, the incidence of oestrus and changes in plasma luteinizing hormone (LH) levels before and after oestradiol benzoate (OB, 15 micrograms/kg body weight) administration on day 22 was compared in 4 MS and 6 Large White (LW) sows. All sows exhibited oestrus in response to OB. Only 1 sow (MS) ovulated in response to OB, became pregnant and farrowed. Mean plasma LH levels before OB were low (MS: 0.38 +/- 0.06 ng LH/ml, LW: 0.29 +/- 0.04 ng LH/ml, ns). LH levels above 2 ng/ml (surge) occurred in 2/4 MS and 2/6 LW sows at 60 +/- 5 h after OB. The MS sow that ovulated had an LH surge level of 4.5 ng/ml plasma at 40 h after OB. These results indicate minor breed differences in the control of LH secretion during lactational anoestrus. PMID- 1449614 TI - Salivary stimulation by chewing gum and its role in the remineralization of caries-like lesions in human enamel in situ. AB - Salivary stimulation elicited reflexively by taste and mastication leads to an increase in the pH, buffering power, and supersaturation of saliva, which can affect beneficially the balance between enamel de- and remineralization in early caries. In a previous study in which a sorbitol chewing gum was used as a salivary stimulant for 20 minutes, five times daily after meals and snacks over a three-week period (during which fluoride toothpaste was used daily), significant remineralization of caries-like lesions in human enamel attached to intraoral appliances in human subjects was observed. In view of the continued public preference for sucrose-sweetened chewing gums, the study was repeated using a sucrose gum. The mean results showed a trend toward remineralization with the use of sucrose chewing gum, which was significant in 10 subjects who chewed for 30 minutes but not in 9 who chewed for 20 minutes. The use of chewing gum after meals and snacks (in the presence of fluoride from toothpaste) can thus enhance the remineralizing potential of the mouth, probably as a result of salivary stimulation. PMID- 1449615 TI - Effect of gum chewing on the pH of dental plaque. AB - Saliva stimulation by gum chewing has been reported to neutralize plaque acidity. We compared the plaque pH response to bread with honey followed by sucrose-or sorbitol-sweetened gum chewing for 20 minutes. Bread and honey was chosen as previous work in our laboratory found this a worst case challenge in terms of the extent and duration of the pH decline. The study design was factorial with: 4 subjects x 2 replicates x 3 treatments. Each subject received each of the 3 treatments: food (bread and honey), food followed by sorbitol chewing gum, and food followed by sucrose chewing gum. Subjects accumulated plaque for 3 days on a partial prosthesis with a glass electrode set in the approximal space in the gap left by a missing first molar. Plaque pH was monitored for 150 min: baseline (0 10), food (11-30), +/- gum chewing (31-50), post-chew monitoring (51-150). ANOVA of mean plaque pH showed no difference between treatments at baseline. Significantly higher pH levels (p < 0.01) were shown with both gums compared to no gum during the chew and post-chew phases. Plaque pH data were also converted to absolute acid values (cH). Food alone produced 1703 mumol/min.; food followed by sorbitol chewing gum produced 53 mumol/min.; and food followed by sucrose gum produced 156 mumol/min. While the post-chew pH curves were not identical for sucrose vs. sorbitol chewing gums, both neutralized plaque acidity, probably due to the induced salivary action. PMID- 1449616 TI - A modified plaque pH telemetry method. AB - Previous plaque-pH telemetry studies reported the acidogenicity of various foods and dietary patterns to estimate potential cariogenicity. To avoid patient discomfort, improve compliance, and minimize electrode malfunctions, we have simplified our telemetry method and compared it to our previously published model. A removable partial prosthesis with a glass electrode set in the approximal space left by a missing first molar was used in 2 subjects. In the modified method, subjects suspended oral hygiene for 3 days, the prosthesis was then installed on the 3rd day, and accumulated plaque was spread on the electrode and covered with gauze for retention. In comparative tests, the same subjects wore the prosthesis in the mouth during plaque accumulation. Test sessions compared the plaque pH response to 4 treatments: a 10% sucrose rinse, a 10% sorbitol rinse, a snack roll with marmalade and coffee, and the snack followed by gum chewing. Overall, pH curves were similar (mean baselines and minimas) and no significant differences in mean pH response were noted between the 2 methods. The modified method improved subject participation, demonstrated greater reliability, and showed Stephan curves comparable to conventional methods. PMID- 1449618 TI - Fast neutron radiation therapy. PMID- 1449617 TI - Two-year longitudinal study of a peroxide-fluoride rinse on decalcification in adolescent orthodontic patients. AB - The purpose of the present study was to determine if once daily use of a 1.5% H2O2 rinse with 0.05% NaF was more effective in preventing decalcification in adolescent orthodontic patients than comparable use of a 0.05% NaF rinse without H2O2, or in patients using no rinse at all. Ninety-five subjects were selected consecutively from adolescents scheduled to receive fixed orthodontic treatment on both dental arches. Three groups were formed that were matched in percentages for age and sex. The first group (control group, n = 35) used a 1100 ppm F toothpaste only. The second group (NaF rinse group, n = 30) used both the same toothpaste and a once daily 0.05% NaF rinse. The third group (H2O2-NaF rinse group, n = 30) used the toothpaste and a once daily rinse containing both 0.05% NaF and 1.5% H2O2. Decalcification was assessed single-blind on the facial surfaces of all erupted teeth at baseline (before appliances were placed), and 3 months after fixed appliances were removed. The difference between baseline and post-treatment decalcification levels determined the incidence of decalcification during orthodontic treatment. Since the first molars were found to have the highest decalcification scores, separate analyses of variance were carried out for the whole mouth and first molar assessments. A p value of less than 0.05 was considered statistically significant. The results showed no significant differences between any of the groups before orthodontic treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449619 TI - Non-Hodgkin's lymphomas in children. I. Patterns of disease and classification. AB - Non-Hodgkin's lymphomas (NHL) are part of an overlapping spectrum of lympho proliferative diseases in childhood. In the first of this 2 part series, the clinicopathological aspects of NHL in childhood are discussed. The rapid progression of disease, the high incidence of micrometastases (over 80%) at diagnosis, and the propensity of hematogenous spread to the bone marrow and the central nervous system (CNS) as well as the clinico-pathologic 'clusters' associated with particular presenting sites distinguish the pediatric forms of disease. Abdominal primary sites most frequently manifest diffuse undifferentiated (Burkitt's or non-Burkitt's) histopathology, B-cell immunophenotype, FAB-L3 cytomorphology and specific karyotypic and/or genotypic alterations of the immuno-globulin genes and the c-myc oncogene. Mediastinal presentation is associated with lymphoblastic histopathology, T-cell immunophenotype and a variety of less consistent karyotypic and genotypic aberrations. Ki-1 lymphoma, a rare subtype of large cell NHL with specific features is often of T cell origin. The requirements for diagnosis, staging and monitoring are presented in the context of the associations between clinico pathological presentation and subsequent behavior. The most frequent sites of disease progression and relapse are involvement of the bone marrow and the CNS. For Burkitt's lymphoma there is a historic perspective and a description of particular epidemiologic, clinical, virologic, immunophenotypic and genotypic features. Cytogenetic and molecular biologic studies of genomic rearrangements are advancing the understanding of oncogenesis, clonality, lineage, and clinical behavior. The capacity to detect and amplify DNA from submicroscopic disease may contribute to prognostic stratification both at diagnosis and during subsequent monitoring. PMID- 1449620 TI - Non-Hodgkin's lymphomas in children. II. Treatment. AB - The prognosis of non-Hodgkin's lymphoma (NHL) in childhood has improved steadily in the last 2 decades. This is primarily the result of increasingly effective chemotherapy regimens tailored to defined and relatively homogeneous prognostic categories and tested in prospective clinical trials. Surgical excision remains of prognostic benefit only when near-total resection can be performed without delay of chemotherapy. The role of radiation therapy is now limited to the treatment of overt central nervous system (CNS) lymphoma, disease unresponsive to chemotherapy, and certain emergencies. Effective 'prophylactic' treatment of the CNS has been achieved in most series by intrathecal and systemic chemotherapy alone. The most relevant modality of treatment is chemotherapy and a very large number of protocols have been published. The origins of current multi-agent regimens stem both from early experience with cyclophosphamide in endemic Burkitt's lymphoma and from therapeutic studies of acute lymphoblastic leukaemia. Sub-stratification of non-localized NHL has produced protocols designed for either lymphoblastic (mostly T cell) or non-lymphoblastic (mostly B cell) categories. While the cure rate for lymphoblastic lymphoma now exceed 70%, the non-localized non-lymphoblastic disease remains a major obstacle to cure. These patients frequently present with large abdominal primaries and are prone to regional as well as hematogenous dissemination. In particular, involvement of the CNS is now considered to be the most adverse prognostic variable in this group. Recently, highly intensive regimens are addressing these obstacles. On the other hand, NHL defined as localized has been shown to be curable in up to 95% of children with the use of simple chemotherapy regimens as short as 6 months in duration. Salvage of patients who relapse during or after chemotherapy remains bleak but cures are possible with regimens incorporating bone marrow transplantation from either an autologous or allogeneic source. Experimental methods, including biologic and immune response modifiers may also offer future promise. PMID- 1449621 TI - [Omega-6 and omega-3 polyunsaturated fatty acids in healthy and sick children under 5 years of age. Part II. Pathologic metabolism]. AB - Today, the long-chain polyunsaturated fatty acids, omega 6 and omega 3, are of special interest to different research groups, all over the world, due to its physiological and metabolic importance. This paper presents different cases of fatty acids deficiency from which the cases of premature low-birth-weight neonates and children under 5 years old presenting severe malnutrition, stand out. In addition, various inherited pathological processes that involve the mechanism of oxidation of these nutrients, are also described. PMID- 1449622 TI - [Differential physical growth during the first year of life. I. Body growth]. AB - Keeping up to date the children growth and development standards, it is a necessity of main order for Health Secretary, because of it is possible an adequate pediatric evaluation. The present study, reports the results of a longitudinal research on growth in children of both sexes and ages from 0 to 1 year of extrauterine life. In all, we got 44 growth measures of the body, head and corporal composition. This report describes the shape of growth body, illustrates the general parameters of growth: stature and weight. Also it includes the dates correspondent to corporal segment growth: sitting height, upper and lower segments; upper extremity, upper arm, lower arm, hand, lower extremity, thigh, leg and foot lengths; ankle height; biacromial, bicrestal, thorax, elbow, wrist, hand, knee, ankle and foot breadths; and thorax depth. Moreover, we report the final increments for corporal segments studied, and the differences on sexual dimorphism. We describe the methodology, socioeconomic and cultural custom results. The sample was classificated within middle lower social class. PMID- 1449623 TI - [Circumcision in the newborn child and risk of urinary tract infection during the first year of life. A meta-analysis]. AB - To assess if neonatal circumcision may decrease the incidence of urinary tract infection (UTI), published papers on these topics were reviewed, to address their methodological shortcomings, and to analyze them in individual and grouped form. A systematic search of the papers on circumcision and UTI was conducted in Index Medicus (1975-1991) and MEDLINE (1988-1991). Six papers were included in the meta analysis because all of them presented original data obtained from groups of patients. All of the elected articles were considered in individual and grouped form to calculate odds ratio (OR) and confidence interval at 95% (CI 95%). The number of patients included in each paper ranged from 112 to 219,775. Clustering of the articles enabled us to obtain a global sample number of 221,799 patients. In each individual article there was a higher risk of UTI in uncircumcised patients (OR from 10.82 to 156.42). Global risk obtained from the six clustered papers was of 13.05 with a CI 95% from 10.86 to 15.70. Uncircumcised males have low risk of UTI during their first year of life, but the risk may decrease even more with circumcision. This conclusion may not be considered as definitive because of the methodological shortcomings of the papers reviewed. Recommendation of routinely circumcision to all newborns in not justified with these data. PMID- 1449624 TI - [Treatment of children with acute diarrheal disease. Knowledge and attitudes of the health personnel]. AB - Diarrheal diseases are still one of the most frequent causes of death due to dehydration in children; lack of information regarding the adequate treatment of diarrhea is the main cause. The results of an inquire sent to 620 physicians and nurses were analyzed to determine the knowledge and attitudes of the health care workers that reside in different diarrheal mortality areas in Mexico. The less professional experience time was correlated with more knowledge in etiology of diarrhea. More physicians than nurses had correct answers regarding the place of diarrheal diseases in child mortality and the correct use of antimicrobial, and other drugs and liquids to prevent and treat dehydration. Most workers did not know the inconvenience of hypertonic solutions to prevent dehydration and the importance of the oral solution flavor. This results suggest that nurses will, be included in clinical training by means of seminars in oral hydration therapy. Furthermore it seems convenient to increase the access to oral hydration solutions as well as the diffusion of its advantages. PMID- 1449625 TI - [Nosocomial infection in the neonatal period at a third level care center]. AB - Results are presented on epidemiologic surveillance of nosocomial infection of all neonates attended at the Instituto Nacional de Perinatologia throughout 1988 1990, reporting rates of 2.1, 2.9 and 5.5 per 100 discharge for each of the years studied. Data are presented in full by service, showing rates of 4.7, 9.5 and 23.0 per 100 discharge in Neonatal Intensive Care Unit (NICU) and 1.5, 3.2 and 6.7 per 100 discharge for Neonatal Intermediate Care (NIC) for the same three years. With respect to type of infection, septicemia, pneumonia and conjunctivitis come as the most frequent causes of infection and Staphylococcus sp coagulase negative (30%), Staphylococcus aureus (27%) and Escherichia coli (7%) as the prevailing microorganisms in nosocomial infection. PMID- 1449626 TI - [Morbidity reduction in preterm newborns fed with milk of their own mothers]. AB - In order to study the effect of feeding on the morbidity, 118 premature newborn, were followed on successive basis; 59 fed with infant term formula (F) and 59 fed with own mother's milk (LH). The patients were classified in 3 groups according to birth weight: I, < 999 g (n = 4/4); II, 1000-1499 g (n = 37/37) and III, 1500 1999 g (n = 18/18), each group F and LH having equal numbers. Growth, morbidity and clinical management were recorded. Necrotizing enterocolitis (P < 0.001), urinary tract infection (P < 0.01) and infectious diarrhea (P < 0.01) were less frequent in LH infants and as a consequence these infants needed less antimicrobial therapy (P < 0.001), nevertheless the human milk contained flora bacteria. The LH infants of group II need fewer red cell transfusions (P < 0.001) and each group was similar and only the babies < 999 g had increments of approximately 15 g/kg/day. This study highlights the importance of feeding the premature infant with own mother's milk; however, the infant growth increments were less than the expected suggesting that human milk must be fortified with proteins and minerals, considering the mothers as a true human milk bank. PMID- 1449627 TI - [Spondyloepiphyseal dysplasia tarda with progressive arthropathy: 2 siblings affected]. AB - We described a Mexican family whose parents were consanguineous. Therefore two children were affected by a progressive arthropathy with deformity in all finger joints, restricted joint mobility and broad major joints. This condition was diagnosed like atypical juvenile rheumatoid arthritis (JRA) because the test for serum rheumatoid factors and antibodies were negative and failed to respond to anti-rheumatoid treatment. However their radiographic studies showed the spine with universal platyspondyly, enlargement epiphyses of the hands, the absence of destructive and the presence of the dysplastic bone changes. These manifestations permit us to do the diagnosis of spondyloepiphyseal dysplasia tarda with progressive arthropathy. In this report we suggest that a complete radiologic study of the patient will allowed to diagnosis this hereditary autosomal recessive entity; likewise it will let us differ of JRA and others polyarticular conditions of childhood. PMID- 1449628 TI - [The Mortality Committee: a hospital need]. AB - Mortality Committees are multidisciplinary teams whose function is to analyze preventable causes of death in order to decrease the death rate, to contribute to the education of medical and paramedical staff and also to advise the hospital authorities in medical and administrative decision-making. In this paper we discuss the activities of the Mortality Committee of the Hospital de Pediatria from May 1989 to May 1991. The review comprised 202 death cases occurred during this period, and was carried out by the medical personnel involved in attending those cases while alive. In 42.5% of these cases the review was supplemented by the necropsy results. Patients' personal data, referral source, status on admission, principal disease, direct cause of death, adequacy of laboratory test and other studies, clinical/pathological correlation and suggestions to improve medical care are discussed. We suggest for every hospital the convenience of having this committee in order to improve the quality of medical care. PMID- 1449629 TI - [Age of onset of spermaturia in 669 children]. PMID- 1449630 TI - [Omega-6 and omega-3 polyunsaturated fatty acids in healthy and sick children under 5. I. Normal metabolism]. AB - The polyunsaturated fatty acids, omega 6 and omega 3, are organic compounds that have to do with the daily caloric intake; the tissue deposits of energy reserve, as well as the general intermediary metabolism of the human organisms and the composition of all the cellular membranes. This article is about its general characteristics: chemical structure, essenciality, biosynthesis, and physiological and metabolical functions; its compounds and metabolites derived; its organic distribution, and the quantity found in food in general. Of all these, special emphasis are made on the essenciality of linoleic and alpha linolenic acids, due to its metabolic importance. PMID- 1449631 TI - [Permanent pacemakers in children. The indications, complications and long-term follow-up]. AB - Definitive pacemakers were placed in 27 children from June 1970 to October 1988. The indication for the pacemakers was congenital auriculoventricular block in 12 patients who were symptomatic; 8 were children with postoperative auriculoventricular block; 4 had developed complete auriculoventricular block from myocardiopathies and 3 from idiopathic sick-sinus syndrome. Two patients died: one 4 months after placement of the pacemaker due to unrelated causes, and the other 14 years later due to fracture of the electrode. There were 23 who were reoperated for different reasons but the most frequent was battery failure in 8 patients and pacemaker malfunction in 4 patients. The electrode was implanted in the epicardium in 21 patients and via subclavian vein into the endocardium in 6 cases. The growth and development physically and mentally were normal during the follow-up of these children. The average follow-up period was 55.6 months. PMID- 1449632 TI - [The perinatal aspects of surviving low-birth weight neonates]. AB - We analyzed prenatal history of 277 live low birth weight infants (less than 2,500 g). We tried to determine some perinatal factors that may be associated with good prognosis in this group of babies. The variables analyzed were: maternal age, number of prenatal visits, complication of pregnancy, mode of delivery, birth weight, sex, gestational age. Apgar score at 1 minute and the neonatal morbidity. The population was divided in 3 groups: 1. Less than 1,000 g, (3).2. 1,000-1,499 g, (37) and 3. 1,500-2,499 g (237). Each group was also divided in appropriate for gestational age (AGA) and small for gestational age (SGA). We found that morbidity and the risk of death, is less in the SGA compared with AGA, associated with better prenatal care, higher birth weight and gestational age. PMID- 1449633 TI - [Morbidity-mortality due to exchange transfusion in a general hospital. A prospective study]. AB - In this prospective study, the complications and mortality appeared in 50 exchange transfusions (ET) were analyzed. The ET were performed in 84% of the cases through a catheter in the umbilical vessels, 22 through both vessels, 10 by vein and 10 by umbilical artery; in the rest of cases by central vein. We found complications in 33% of the cases. Cardiac arrhythmia (23 cases) was the most frequent complication; also metabolic complications in 20 cases, septic complications in 10 cases (8 cases of omphalitis and 4 of sepsis were included), 8 cases of necrotizing enterocolitis and 3 of bleeding were found. Some of the newborns has 2 or more complications at the same time. The total lethality rate was 4% which occurred in 2 preterm infants with critical state. Our finding suggest that morbidity due to ET is highest than previously reports and maybe the mortality is due to the critical state of patients more than the ET. PMID- 1449634 TI - [The degree of agreement of the clinical and the histopathological diagnoses in a tertiary medical care pediatric hospital]. AB - In Pediatric Hospital, from the National Medical Center, of the Mexican Institute of Social Security were analyzed 96 histological pieces: 59 biopsies, 21 surgical material and 16 slides. There were showed the agreement rate between clinical diagnosis and the end histopathological report from the Pathology Department. The higher correlation rate were with biopsies (83%) and surgical material (81%) and the lowest rate were with slides samples (69%). There were not statistical difference in the 3 study groups (P greater than 0.05). The overall concordance with the clinical diagnosis were 82%. The overall concordance with the 3 study groups were 80%. It is concluded what agreement rate was satisfactory in biopsies and surgical material and the agreement rate measure is an actual parameter in evaluation of clinical competence and also in the evaluation of medical care quality. PMID- 1449635 TI - [Congenital cystic adenomatoid malformation of the lung. A report of 12 cases]. AB - The congenital cystic adenomatoid malformation of the lung is uncommon. In the Hospital Infantil de Mexico Federico Gomez, 12 cases have been seen over a period of 31 years, which points out how rare this malformation is. There was a male predominance, and 75% of the patients had symptoms by 8 months of age. The main complaints were progressive respiratory failure in the newborn period and recurrent lung infection in older children. Treatment was surgical in all cases. There was only one fatality due to cardiac failure. PMID- 1449636 TI - [Splenic abscesses. A case report and review of the literature]. AB - This is a report of a case of a 3-year-old boy who developed splenic abscesses after a mild plantar wound. His initial complains were fever and several distal cutaneous abscesses (septic emboli). Multiple cultures for bacteria, fungi, mycobacterium and anaerobes were performed, but all were negative. In spite of an energetic antimicrobial treatment, he continued with high fever. Echocardiography was normal. Two weeks later, a thoracic radiography showed the left hemidiafragm was elevated and a small pleural effusion. An abdominal echosonography showed multiple hypoechoic splenic lesions, and this finding was confirmed by magnetic resonance imaging. After splenectomy, the patient healed and was discharged. Anatomopathological examination of the spleen showed eight pyogenic abscesses of different size. The causal agent was not isolated. PMID- 1449637 TI - [Rapid intravenous rehydration in acute diarrhea]. AB - With the use of oral rehydration, the need for the use of endovenous rehydration has decreased considerably. Albeit, the use is still necessary in severely dehydrated patients or when oral rehydration fails. Textbooks produced in developed countries recommend slow administration of fluids to correct dehydration in 12 to 24 hours. In developing countries, due to the great number of severely dehydrated patients, this approach is not useful. We developed, during the last 20 years, an approach to intravenous rehydration that permits rehydration of the severely ill patient in a much shorter time (2 to 3 hours) and permits an early refeeding. It can be used in all patients, even newborns or malnourished. No laboratory tests are necessary. Only a small number of simple and readily available solutions are used to prepare the electrolyte mixtures. PMID- 1449638 TI - Haloperidol does not alter expression of ethanol-induced conditioned place preference. AB - A recent experiment (Risinger et al., Psychopharmacology, 107 (1992) 453-456) has shown that haloperidol does not prevent acquisition of ethanol-induced conditioned place preference, suggesting that dopaminergic mechanisms do not mediate the primary rewarding properties of ethanol. The present experiment examined whether haloperidol would prevent the expression of conditioned reward to ethanol-paired stimuli using the place conditioning paradigm. DBA/2J mice received four pairings of a tactile stimulus with ethanol (2 g/kg, IP). A different stimulus was paired with saline. Before preference testing, different groups received one of three doses of haloperidol (0, 0.05 or 0.1 mg/kg); ethanol was not given. Haloperidol produced a dose-dependent decrease in locomotor activity, but did not affect conditioned place preference. These results suggest that expression of ethanol-induced conditioned place preference is mediated by non-dopaminergic mechanisms. PMID- 1449639 TI - The effects of V4 lesions on the visual abilities of macaques: shape discrimination. AB - Monkeys with bilateral ablation of cortical visual area V4 were compared with unoperated controls for their ability to relearn postoperatively a series of preoperatively acquired two-choice visual discrimination problems. The animals with V4 lesions were impaired on relearning to discriminate between different shapes, and discrimination between identical shapes presented at different orientations was also impaired. Some of the deficits were consistent with disrupting the input to inferotemporal cortex, but discrimination of a subset of the stimuli is known to be unaffected by inferotemporal cortex lesions and could not be explained in the same way. To clarify the nature of the deficit, and to test the hypothesis that shapes differing in orientation are analyzed in the occipitoparietal processing pathway, animals with V4 lesions were also compared to normals on their ability to acquire a version of the landmark task. The V4 animals performed as well as the control animals on this task. The results suggest that V4 is important for the shape discrimination abilities that survive inferotemporal cortex lesions. The role of V4 in shape analysis is discussed in the light of recent evidence that V4 neurones are modulated by visual attention. PMID- 1449640 TI - Modulation of visually evoked responses in units of the ventral lateral geniculate nucleus of the rat by somatic stimuli. AB - Single unit activity was recorded from the ventral part of the lateral geniculate nucleus (vLGN) in rats anaesthetized with urethane. Most of the cells located laterally in the nucleus were excited by light. The studied vLGN neurones did not respond to electrical stimulation of the tail, but about half of them changed their response to light significantly when the light flash was paired with the electrical stimulation. When the tail stimulus preceded the light, the changes consisted in a pronounced facilitation of flash-evoked activity. When the electrical stimulus was applied after the flash in a forward conditioning paradigm, facilitations were less pronounced and responses of some neurones were suppressed. These results are in contrast to those of similar experiments on the dorsal LGN, neurones of which were mainly facilitated by the conditioning paradigm. Thus, light-evoked activity of ventral geniculate cells can be enhanced by arousal-related processes. PMID- 1449641 TI - Intrinsic and extrinsic influences on play fighting in rats: effects of dominance, partner's playfulness, temperament and neonatal exposure to testosterone propionate. AB - Play fighting is a frequent activity of juvenile rats and appears to show marked variability amongst individuals in that some rats play a great deal and others very little. This study attempted to identify some of the factors involved in producing this individual variability. The major influence over an individual's frequency of play as a juvenile was found to be the frequency of play by the partner. That is, play appears to be contagious, in that a high playing animal stimulates its partner to play frequently as well. In male juveniles, but seemingly not in female juveniles, the subsequent adult status of one partner as dominant influences the subordinate-to-be to initiate more playful contacts. In addition to these extrinsic influences, however, there appear to be intrinsic factors that influence whether an individual is a high or low playing animal. One intrinsic factor appears to be 'boldness', so that bolder animals tend to initiate more playful contacts. Higher players tend to be more susceptible to the stereotypy-inducing effects of the dopamine agonist, apomorphine, and tend to be more dependent upon the playful activity of the partner to maintain their own high levels of play. Both of these characteristics are consistent with other studies comparing bold and timid rats. Boldness, however, only seems to influence how much play a rat will exhibit, not how much play it is capable of exhibiting. Neonatal testosterone augmentation increases juvenile play fighting but not apomorphine susceptibility, suggesting that a high player need not be a bold animal. The total frequency of play an individual is capable of initiating appears to depend upon perinatal exposure to androgens. Boldness and the playfulness of the partner appear to modulate the expression of this hormonally set value. PMID- 1449642 TI - Role of pups' ultrasonic calls in a particular maternal behavior in Wistar rat: pups' anogenital licking. AB - Stimuli from pups maintain maternal behavior in the postpartum period. Olfactory cues are strongly involved in a particular component of maternal behavior: anogenital licking (MAGL). In addition to the olfactive stimulus, ultrasonic calls from pups are critical in ensuring pup survival. Pups emit vocalizations in distress situations. In a first experiment, pups' calls are recorded around MAGL sequences. In 2 out of 3 cases these calls appear to induce MAGL behavior from the dam with preputialectomised pups as well as with intact pups, but preputialectomised pups alone call again at the end of MAGL sequences. In a second experiment, ultrasonic calls from pups emitted just before AGL sequences were recorded and played back to dams in a glass-dish selection test. Whatever the pups' treatment (preputialectomised or sham), dams showed the specific ingestive behavior towards filter paper impregnated with dodecyl propionate (DP) when auditory cues (pups' ultrasonic calls) and olfactory cues (DP) were combined. The coordination of pups' ultrasonic calls and anogenital odor in MAGL behavior is discussed, ultrasonic calls might be an inducing factor and DP the regulating factor. PMID- 1449643 TI - Limbic seizures, but not kindling, reversibly impair place learning in the Morris water maze. AB - We investigated the effects of kindling and kindled seizures in different limbic structures on place and cue learning in the Morris water maze. The triggering of seizures by stimulation of the perforant path, septum, or amygdala prior to daily training impaired place learning, but had little effect on visible platform training or swim speed. Seizures triggered by stimulation of the medial perforant path after daily training also impaired place learning. Conversely, place learning proceeded normally in rats tested 24 h after kindling triggered by stimulation of the perforant path, septum, or amygdala, indicating that kindling per se does not affect place learning. Each group was able to learn the location of a reversed platform when pretraining seizures were discontinued; and perforant path and septal kindled rats, but not amygdaloid kindled rats, were impaired at learning the location of a reversed platform when seizures were triggered before training. The results confirm previous reports that limbic seizures produce amnesia, but they contradict the finding that hippocampal kindling impairs learning on tasks sensitive to hippocampal lesions. PMID- 1449644 TI - Neural correlates of frog calling: production by two semi-independent generators. AB - The anterior preoptic nuclei of the isolated brainstem of male, Northern leopard frogs (Rana p. pipiens) were stimulated electrically and neural correlates of mating calling recorded from the rhombencephalic mating calling pattern generator. Lesions of discrete areas of the brainstem showed that the mating calling generator is separable into two generators, the pretrigeminal nucleus and the classical pulmonary respiration generator (which is approximately co extensive with the motor nuclei IX-X). Each of these still can produce pulses when isolated from the other. Their interaction changes the expiratory phase of breathing into the vocal phase of calling. All stages of intermediates between these phases could be seen. An updated and simplified model of call production and evolution is presented. PMID- 1449645 TI - Metabolic activity in the hyperstriatum of 2-day-old chicks during optomotor and contrasting visual stimulation. AB - Our earlier report of differences in metabolic activity within the visual regions of the hyperstriatum and ectostriatum, in 2-day-old chicks compared with 23-day old chicks, suggested that two visual pathways within the visual system develop at different rates. Here we have investigated whether the demands of varying visual environments will increase the activity of the hyperstriatum accessorium (HA) in 2-day-olds. Metabolic activity in the HA was monitored in 2-day-old chicks by the radioactive 2-deoxyglucose technique during monocular stimulation with three different visual environments: moving stripes in a rotating drum, which induced eye and head movements, a featureless white environment, and the complex visual environment of the home cage with other chicks. Although a small but significant level of activity was found in HA in the hemisphere opposite the open eye, the activity did not vary with the visual treatment. On the other hand, a raised level of activity in the hyperstriatum dorsale (HD) appeared in chicks viewing the rotating stripes, indicating that at this age the thalamo hyperstriatal pathway may be involved in processing whole-field visual movement. The optomoter environment also produced high activity in the medial hyperstriatum ventrale (MHV), a region that has been implicated in memory formation of imprinting. We suggest that during the sensitive period for imprinting, HA may either have not developed its fully functional capacity, or that following or during imprinting it is actively shut down to protect itself and associated regions from interfering visual input. In contrast to the 2-day-olds, 17-day-old chicks in a visually rich cage environment, had high levels of activity in HA, demonstrating that the functional maturation of the HA, related to performance in the cage environment, is complete at least 6 days earlier than previously observed. PMID- 1449646 TI - Auditory working and reference memory can be tested in a single situation of stimuli for the rat. AB - The comparison of working and reference memory is one of the most valuable research angles for revealing the precise neural mechanisms of memory. The present study introduces a method to test both auditory working and reference memory during a short period in the rat. The apparatus and stimuli are identical for both memory tasks. High and low tones, between which lies a 5-s interval, are continuously presented. The task for working memory is a continuous nonmatching to-sample. The rat makes go and no-go responses to indicate whether the current tone is the same as (match) or different from (nonmatch) the preceding tone. The task for reference memory is a continuous discrimination. The rat makes go responses on high-tone trials and no-go responses on low-tone trials. With alternate training in these tasks, the rat comes to perform well in both tasks. The rat can only know which task is employed in a given session from its own response-reward contingency during the early trials of each session. PMID- 1449647 TI - Pressure on the snout immobilizes the spontaneously active, scopolaminized, and amphetaminized hyperactive rat. AB - Rats that are brought into a novel environment or that are given stimulants or anti-muscarinic drugs exhibit high levels of motor activity. Application of moderate pressure on the sides of the snout of such rats results in immediate cessation of all movements for extended time periods. Hippocampal electrocorticograms show that hippocampal slow wave activity during such induced immobility is equivalent to the hippocampal slow wave pattern typically associated with spontaneous immobility. However, neocortical activity following scopolamine administration contains more 2-6 Hz irregular activity during spontaneous than induced immobility. PMID- 1449648 TI - The effects of early experience on callosal development and functional lateralization in pigmented BALB/c mice. AB - A proportion of animals of the BALB/c inbred mouse strain have an unusually small (sometimes absent) midsagittal area of the corpus callosum (CC). In this study, we used a large sample of both males and females (total n = 198) from a pigmented congenic BALB/c line to investigate the relations among preweaning handling, area of CC, and direction and degree of lateralization as measured by Collins' paw preference task. Twenty litters were handled daily from the day after birth until day 25 (weaning) according to Denenberg's procedure and 18 litters were left undisturbed until weaning. All animals were tested for degree and direction of paw preference in a modification of Collins' apparatus at about 60 days and measures taken on CNS structures at 100 days of age. There were no handling or sex effects on degree or direction of paw preference or on the extent of CC defects, but for animals in the normal range (CC > or = 0.7 mm2), those which had been handled had significantly smaller callosa. No significant differences were detected between right and left hemisphere weights, and these measures did not appear to be related to the behavioural measures. There was no significant correlation between CC area and degree of paw preference nor was there any relationship between total agenesis and degree of handedness. This last result is particularly interesting in light of recent evidence that ILn/J mice, all acallosal, are exclusively ambilateral. PMID- 1449649 TI - Spatial deficits and hemispheric asymmetries in the rat following unilateral and bilateral lesions of posterior parietal or medial agranular cortex. AB - Studies of spatial behavior in both the human and non-human primate have generally focused on the role of the posterior parietal and prefrontal cortices and have indicated that destruction of these regions produce allocentric and egocentric deficits, respectively. The present study examined the role of the rodent analogs of these regions, the posterior parietal (PPC) and medial agranular (AGm) cortices, in egocentric and allocentric spatial processing, and whether spatial processing in rodents is organized in a hemispatial and/or lateralized manner as has been found in the primate. Eighty male rats receiving either a unilateral or bilateral lesion of AGm or PPC were examined on an egocentric (adjacent arm) or an allocentric (cheeseboard) maze task. The results indicated that PPC and AGm have dissociable spatial functions. Bilateral AGm destruction resulted in egocentric spatial deficits, and unilateral AGm operates demonstrated an intermediate deficit. In contrast, bilateral PPC operates demonstrated a severe deficit in allocentric processing. In addition, there were lateralized differences in the performance of unilateral PPC operates. While right PPC lesions resulted in a significant deficit on the allocentric task, no such deficit was seen in left PPC operates. In addition, neither unilateral AGm nor unilateral PPC operates demonstrated a hemispatial impairment on either the egocentric or allocentric tasks. PMID- 1449650 TI - Does the type of prehension influence the kinematics of reaching? AB - Kinematic studies have indicated that when a subject reaches to grasp an object, the movement consists of two primary components: (a) a transport phase whereby the hand is brought towards the object and (b) a grip phase whereby the hand changes shape in anticipation of the grasp. Using a visual perturbation paradigm, we investigated the effect of different grip component strategies upon the transport phase. The distal strategy was determined by the size of the object to be grasped: for the small object (1.5 cm o.d.) subjects naturally adopted a precision grip between the index finger and thumb; for the large object (6 cm o.d.) subjects used a whole hand prehensile grip. During 20% of the reaching trials the perturbation was introduced by unexpectedly changing the object size. The results showed that corrections to the distal program in response to the perturbation were preceded by changes in the deceleration phase of the proximal component. The data supported previous findings of two visuo-motor channels for this prehensile movement but indicated that when unanticipated shifts of only the distal program are required, both channels show modifications. PMID- 1449651 TI - Pimozide prevents the development of conditioned place preferences induced by rewarding locus coeruleus stimulation. AB - Electrical stimulation in the vicinity of the cell bodies of the locus coeruleus (LC) has been shown to support self-stimulation behaviors in rats. In the present study, a Conditioned Place Test, sensitive to both rewarding and aversive qualities of brain stimulation, was employed to determine (a) whether rewarding locus coeruleus stimulation would result in place preferences and (b) if so, whether dopamine receptor antagonism would affect the development of such place preferences. Animals were pretreated with pimozide (0.0, 0.5 or 1.0 mg/kg) prior to exposure to two distinctive environments only one of which was paired with locus coeruleus stimulation. Rats that received vehicle injections prior to stimulation/place pairings developed strong preferences for the stimulation paired environment while those animals pretreated with 0.5 mg/kg pimozide showed no reliable shift in preference from baseline performance. Additionally, animals injected with the 1.0 mg/kg dose of pimozide exhibited mild place aversions to the stimulation-paired environment. It is hypothesized that dopamine neurotransmission is important for the rewarding effects of locus coeruleus stimulation without which such stimulation appears to be aversive. PMID- 1449652 TI - Medial frontal cortex lesions impair the aiming component of rat reaching. AB - This study examined the contribution of medial frontal cortex (the medial portion of supplementary motor cortex, or Fr1) to the performance of rats on trained, or 'skilled', reaching tasks. Unilateral medial frontal cortex lesions moderately impaired reaching success on a task that demanded accuracy but they did not impair performance on a less demanding reaching task nor did they affect limb preference. Kinematic analyses indicated that the aiming component, in which the forearm of the limb is aligned along the midline of the body by adduction of the elbow, was chronically impaired. Rather than adducting the elbow to aim, the rats used a number of limb and whole body postural adjustments to compensate for incomplete or absent aiming. That medial frontal cortex is involved in the execution of at least one component of skilled reaching implies that a larger area of frontal cortex is involved in skilled limb movement than has been suggested by previous studies. The results also suggest that the different regions of frontal cortex may each have a relatively selective involvement in the execution of only a subset of the movements comprising a reach. PMID- 1449654 TI - Comparison among three screening methods for aflatoxigenic isolates. AB - Seventy-six isolates of Aspergillus flavus, which were isolated from one hundred food stuffs in Zhejiang Province, were detected with RMC, AMCS and APA methods for aflatoxigenicity. The rates of toxigenic isolates detected by the three methods were 11.8%, 18.4% and 9.2% respectively. There were twenty toxigenic isolates detected by the three methods (26.3%) AMCS method was better than other methods. False negatives appeared in all methods. False positive appeared in both AMCS method and APA method. It was suggested that AMCS method may be a safe, simple and reliable method for screening toxigenic isolated if some aspects were improved. PMID- 1449653 TI - Protective effects of dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl 2,2'-dicarboxylate on damages of isolated rat hepatocytes induced by carbon tetrachloride and D-galactosamine. AB - The protective effect of biphenyl dimethyl dicarboxylate (DDB) on chemically induced damages was studied in isolated suspended rat hepatocytes. The experimental results showed that DDB (200 micrograms/10(6) cells) efficiently protected the hepatocytes against carbon tetrachloride (CCl4 10 mmol.L-1) and D galactosamine (1 mmol.L-1) induced damages. Membranal lipid peroxidation (malondialdehyde, MDA formation) and glutamic pyruvic transaminase (GPT) release from the hepatocytes were markedly decreased. The damage of the cell surfaces of the hepatocytes were also reduced as seen under a scanning electron microscope (SEM). Pretreatment with DDB (300 mg.kg-1) orally ameliorated the reduction of liver glycogen and blood glucose caused by ip injection of D-galactosamine (800 mg.kg-1) in mice. When normal rats were given DDB 300 mg.kg-1 once daily for 10 d, the free ribosomal protein and RNA in the liver increased significantly. These results indicate that DDB is of beneficial effects on both damaged and normal hepatocytes. PMID- 1449655 TI - Protective effect of dimethyl-4,4'-dimethoxy-5,6,5', 6'-dimethylene dioxybiphenyl 2,2'-dicarboxylate (DDB) against carcinogen-induced rat liver nuclear DNA damage. AB - The protective effect of DDB against carcinogen-induced DNA damage was examined in the present investigation. Preincubation of rat liver nuclei with DDB (1 mmol.L-1) resulted in 60% inhibition of binding of 3H-benzo(a)pyrene to nuclear DNA. Unscheduled DNA synthesis (UDS) induced by aflatoxin B1 (10(-7) mol.L-1) in freshly isolated rat hepatocytes was also inhibited by DDB (10(-6)-10(-3) mol.L 1). Oral administration of DDB at 200 mg.kg-1 once daily for 3 d induced a significant increase of liver cytosol glutathione-S-transferase and microsomal UDPG-transferase activity in mice. These results indicate that DDB is able to directly or indirectly antagonize certain carcinogen-induced DNA damages. PMID- 1449656 TI - Effect of nickel on some aspects of protein metabolism in selected organs of the freshwater mussel Lamellidens marginalis. AB - The levels of soluble, structural and total proteins, and the activities of A1AT and AAT decreased along with an increase in the levels of free amino acids and the activity of protease in the ctenidium, hepatopancreas and foot of the freshwater mussel L. marginalis after 1, 2, 3 and 4 d of exposure to a lethal concentration (115 mg.L-1) of nickel. But the activity of GDH and the level of urea decreased in the hepatopancreas and increased in the ctenidium and foot. A reverse trend was observed in the level of ammonia. In a sublethal concentration (23 mg.L-1), the levels of soluble, structural and total proteins and ammonia decreased in these three organs of the mussel after 1, 5, 10 and 15 d of exposures, with an increase in the levels of free aminoacids, urea and in the activities of protease, A1AT, AAT and GDH. The extent of these changes differed in degree depending on exposure period in the lethal and sublethal concentrations. The results are discussed in order to arrive at the degree of metal stress on the overall nitrogen metabolism of the mussel according to the period of exposure to lethal and sublethal concentrations of nickel. PMID- 1449657 TI - Quantitative risk assessment for lung cancer from exposure to metal ore dust. AB - To quantitatively assess risk for lung cancer of metal miners, a historical cohort study was conducted. The cohort consisted of 1113 miners who were employed to underground work for at least 12 months between January 1, 1960 and December 12, 1974. According to the records of dust concentration, a cumulative dust dose of each miner in the cohort was estimated. There were 162 deaths in total and 45 deaths from lung cancer with a SMR of 2184. The SMR for lung cancer increased from 1019 for those with cumulative dust dose of less than 500 mg-year to 2469 for those with the dose of greater than 4500 mg-year. Furthermore, the risk in the highest category of combined cumulative dust dose and cigarette smoking was 46-fold greater than the lowest category of dust dose and smoking. This study showed that there was an exposure-response relationship between metal ore dust and lung cancer, and an interaction of lung cancer between smoking and metal ore dust exposure. PMID- 1449658 TI - A study on genotoxicity of cooking fumes from rapeseed oil. AB - The present article reports the genotoxic potential of rapeseed oil cooking fume investigated by a battery of short-term tests (Ames test, SCE/V79 in vitro and mice micronucleus in vivo test). The results showed that the cooking fume contained mutagenic activity. In the presence of S9 mix, an increase in the number of the Salmonella TA98 was observed at doses ranging from 1.0 to 5.0 mg/plate, and the SCE frequencies of V79 cell were markedly raised at doses ranging from 0.05 to 0.5 mg.ml-1. The positive result was also obtained in mice micronucleus assay, the mice had inhaled the cooking fume a week earlier. The frequency of mice bone marrow MN-PCE was increased and it showed a remarkable time-dose-response relationship during the 4 weeks exposure. The results suggested that this cooking fume exposure may be a risk factor of lung cancer in Chinese women. PMID- 1449659 TI - Thyrotoxicity of the chlorides of cadmium and mercury in rabbit. AB - Exposure to heavy metals such as cadmium and mercury is of immediate environmental concern. The present study was aimed at establishing a direct relationship between heavy metal poisoning and thyroid dysfunction. Cadmium and mercury treatment at LD50 levels resulted in severe thyrotoxicosis in the rabbit. Within 24 h of intramuscular administration of cadmium chloride 15 mg.kg-1 body weight (bw) and mercury chloride 20 mg.kg-1 bw, thyroid peroxidase activity increased significantly over the control with a concomitant rise in the triiodothyronine (T3) titre. On the other hand, there was a remarkable fall in the thyroxine (T4) level, and the T3/T4 ratio was high as compared with the control. Evidence indicates that acute heavy metal lethality will induce immediate hyperthyroidism. It is suggested that T3-toxicosis may be produced by a preferential synthesis of T3 and/or preferential deiodination of T4 to T3. Measurement of T3 and T4 levels may thus be utilized as a reliable indicator of heavy metal lethality. PMID- 1449660 TI - Metal induced inhibition of photosynthesis, photosynthetic electron transport chain and ATP content of Anabaena doliolum and Chlorella vulgaris: interaction with exogenous ATP. AB - This study demonstrates a concentration dependent inhibition of carbon fixation, O2 evolution, photosynthetic electron transport chain and ATP content of A. doliolum and C. vulgaris by Cu, Ni and Fe. Although the mode of inhibition of photosynthetic electron transport chain of both the algae was similar, PS II depicted greater sensitivity to the test metals used. The toxicity in both organisms was Cu > Ni > Fe. A. doliolum was, however, more sensitive to Cu and Ni, and C. vulgaris to Fe. Toxicity was generally dependent on metal uptake, which in turn was dependent on their concentrations in the external medium. A partial restoration of nutrient uptake, carbon fixation, and enzyme activities following supplementation of exogenous ATP suggests that ATP regulates toxicity through chelation. PMID- 1449661 TI - An out-break of epidemic dropsy in the Barabanki District of Uttar Pradesh, India: a limited trial for the scope of antioxidants in the management of symptoms. AB - An attempt was made to explore the scope of the bio-antioxidants in the management of symptoms of epidemic dropsy caused by argemone alkaloids, sanguinarine and dihydrosanguinarine. The study was performed on 24 randomly selected epidemic dropsy cases who consumed argemone contaminated mustard oil. On examination the cases revealed characteristic pitting edema over limbs (95.8%) accompanied by tenderness (79.2%) and diffuse erythema (95.8%). Tachycardia was present in 1/3 of the examined cases while elevated jugular venous pressure was seen in over 40% of the cases. In two of the cases, reddish-purplish blotches over lower limbs, not raised and which blanched on pressure, was an unusual feature. Chest X-ray revealed pulmonary congestion in 5 cases. ECG performed in 3 cases with severe breathlessness, showed non-specific ST-T changes most marked in L2,L3, avF and V2-V6 which reversed on recovery. Treatment with a combination of antioxidants, riboflavin and tocopherol showed improvement in pain in lower limbs (75%), edema (83.3%) and erythema (66.6%). PMID- 1449662 TI - Studies of lead exposure on reproductive system: a review of work in China. AB - This paper, based on a review of a series studies conducted in China from 1978 through 1991, describes the possible links between low level lead exposure and the adverse effects on reproductive system. Effects on menstrual status and pregnancy outcome manifested mainly as higher prevalences of menstrual disturbance, spontaneous abortion and threatened abortion in exposed females. Transfer of lead via placenta and human milk was shown by higher lead levels in milk and blood of infant. Impairment of male reproductive function was observed as decreased volume of ejaculation, prolonged latency of semen melting, reduced total sperm count and alive spermatozoa, retarded sperm activity as well as lowered density of semen fluid in exposed male workers with Pb-B over 40 micrograms.dl-1. In addition, poorer performance of WISC-R test was revealed in children with Pb-B level over 30 micrograms.dl-1, and retarded physical development was observed in children with Pb-B over 20 micrograms.dl-1. Therefore, health surveillance including the assessment of adverse effects on reproductive system of both female and male lead exposed workers should not be ignored. Furthermore, safety exposure limit of work place, particularly for female workers of child-bearing age, should be developed. PMID- 1449663 TI - Minimally invasive lumbar disc surgery. PMID- 1449664 TI - Total overall management and surgical outcome after aneurysmal subarachnoid haemorrhage in a defined population. AB - It was possible from a geographically well-defined region to detect all patients sustaining an aneurysmal subarachnoid haemorrhage. Different outcomes were measured and compared with other published series. Twenty-one per cent of all our patients at risk were never seen by a neurosurgeon. By adding further 20% of dead patients to the management series a total overall outcome, i.e. from all 'patients at risk', could be calculated, making comparison between different series easier. Favourable outcomes in the three groups (total overall, total management and surgical) as measured with the Glasgow Outcome Scale at 12 months were 46, 58 and 69%, respectively, in this series. In a super selected group such as good-grade patients (Hunt and Hess I-II) at surgery favourable results were seen in 87% of the patients at 6 months follow-up. The favourable outcome in the total overall, total management and surgical groups increased between 6 and 12 months follow-up by 1, 1 and 2%, respectively, as compared to 4, 5 and 6%, respectively, between discharge and 6 months follow-up. The time of follow-up to measure outcome should not be shorter than 6 months in aneurysm cases. It is emphasized that all patients drop-outs from the initial 'patient at risk' should be identified. PMID- 1449665 TI - Smoking and subarachnoid haemorrhage: a case control study. AB - Retrospective and epidemiological studies have suggested that smoking increases the risk of developing aneurysmal subarachnoid haemorrhage (SAH). During 1990, 217 patients presenting to the Mersey Regional Neurosurgical unit with spontaneous SAH were prospectively studied. Smoking habits of patients with SAH were compared with age, sex and occupation matched controls. The relative risk of spontaneous aneurysmal SAH for smokers was twice that of non-smokers (p < 0.001). Management outcome at 6 months following aneurysmal SAH was similar for smokers and non-smokers (p = 0.43) but smokers had more postoperative pulmonary complications requiring ventilation. Significance was tested with chi-square tests. PMID- 1449666 TI - Interstitial white matter brain oedema does not alter the electroencephalogram. AB - An experimental study was performed to determine the effects of interstitial white mater oedema on the electroencephalogram (EEG). Using both rodent and feline infusion models of focal brain oedema no difference was found between the EEG waveforms recorded epidurally from the infused and control hemispheres. It is concluded that where focal slow-wave EEG abnormalities overlie oedematous brain the EEG abnormalities are not primarily related to the brain oedema but arise from either local biomechanical or other pathophysiological mechanisms. PMID- 1449667 TI - Effect of unilateral pre- and postganglionic lesioning of the trigeminal nerve on the development of cerebral vasospasm in the squirrel monkey: angiographic findings. AB - Bilateral carotid angiography was performed in the squirrel monkey before and after unilateral pre- and postganglionic trigeminal lesioning. A unilateral postganglionic lesion caused a significant constriction of about 27% of the ipsilateral cerebral arteries, while a preganglionic lesion did not change the baseline arterial diameter. Following a subarachnoid haemorrhage (SAH) the degree of vasoconstriction in the animals with a preganglionic lesion did not differ significantly from that seen in controls. In the postganglionically lesioned animals, the vasoconstriction was more pronounced (12% at both 10 min and 6 days post SAH) on the lesioned as compared with the non-lesioned side. At day 6 post SAH the degree of vasoconstriction was 19% more pronounced on the lesioned side in post- as compared with the preganglionically lesioned animals. There was no difference in the degree of spasm on the non-lesioned side between the two groups. The findings indicate that the trigeminal system has both a peripheral and a central function. The peripheral, or axon reflex mechanism, exerts a tonic effect on the cerebral vessels. Following a SAH the axon reflex seems to attenuate cerebral vasospasm. PMID- 1449668 TI - Hyponatraemia in neurosurgical patients: diagnosis using derived parameters of sodium and water homeostasis. AB - Seventeen unselected, consecutive patients with intracranial disease and accompanying hyponatraemia were studied. All would previously have been diagnosed as having the syndrome of inappropriate antidiuretic hormone (ADH) secretion on the basis of spot plasma/urinary electrolyte testing with the application to them of existing standard laboratory criteria. Timed urinary collections and matching plasma samples were available in all but three cases for the derivation of creatinine, osmotic and free-water clearances, tubular reabsorbed water, and fractional water and sodium excretions. In a number of patients the plasma renin, aldosterone and ADH levels were also assayed. On the basis of the overall findings, 13 patients were diagnosed as in fact having a salt-wasting state whilst in only four patients was the diagnosis of inappropriate ADH secretion (SIADH) substantiated. It is suggested that obtaining simple derived parameters of sodium and water homeostasis can add significantly in differentiating between these quite opposite syndromes. PMID- 1449669 TI - Microsurgical management of craniopharyngiomas. AB - A retrospective analysis of 34 patients who underwent microsurgical therapy for craniopharyngioma from 1975 to 1989, a period when CT imaging was routinely used, is presented. Mean follow-up was 6.4 years with no patients lost to follow-up. Those who underwent subtotal resection with adjuvant radiation had a significantly better recurrence-free interval compared with those who either underwent total or subtotal surgical resection only (p < 0.05 and p < 0.025). Among patients treated with surgery alone, the total resection group had a recurrence rate of 20% and those with a subtotal resection 60%. Those with subtotal resection and radiation had a 12% rate of recurrence. Endocrine and visual deficits were common after surgery. Based on this review, our results suggest that with a policy of attempted total resection where possible, subtotal removal along with adjuvant radiation, in cases where total resection was deemed unsafe, may be more effective than aggressive total resection alone as the initial management of craniopharyngioma. PMID- 1449670 TI - A simplified technique for lengthening peritoneal catheters. AB - Existing techniques for lengthening a peritoneal catheter require a formal laparotomy, and exploration for the catheter which is then extended by the addition of a necessary length. We describe a simplified technique which is quicker and which in co-operative patients can be done under local anaesthesia on an out-patient basis. In this technique the peritoneal catheter along with its fibrous sheath is dissected and after opening the sheath an additional length is added. The elongated catheter is replaced through the same tubular sheath into the peritoneal cavity. PMID- 1449671 TI - Cystic cerebellar schwannoma. AB - Cystic cerebellar schwannoma is a rare tumour which may not be considered when a low attenuation computed tomographic (CT) lesion is seen in the cerebellar parenchyma. Since the origin of the Schwann cell in the cerebellar parenchyma is conjectural, immunohistochemical techniques are necessary for a diagnosis. PMID- 1449672 TI - MRI in the diagnosis of spinal extradural angiolipoma. AB - We report the case of a 68-year-old woman with a 1-year history of progressive spastic paraparesis, due to an extradural angiolipoma of the mid-thoracic spine. The MRI appearance of the angiolipoma is reported here for the first time. This appearance is characteristic, allows preoperative diagnosis and assists planning of the surgical approach. PMID- 1449673 TI - Cerebral infarction due to Aspergillus arteritis following glioma surgery. AB - Cerebral infarction due to fungal arteritis is an uncommon complication of neurosurgical operations and adjuvant immunosuppressive therapy, including long term steroids. If unrecognized, the neurological deterioration which ensues may be mistreated by increasing the dose of steroids. A case of a 38-year-old Caucasian male who had no obvious immune deficiency or fungal infection prior to a craniotomy for cerebral tumour is described in whom perioperative aspergillus infection resulted in cerebral arteritis and extensive cerebral infarction with a fatal outcome. Long-term steroid therapy used in the management of cerebral tumours may carry an increased risk of systemic or cerebral fungal infection. The possibility of cerebral mycosis (arteritis) and dangers of its non-recognition are highlighted. PMID- 1449674 TI - Vein of Galen aneurysm presenting in middle age. AB - A vein of Galen aneurysm occurring in a 55-year-old woman is presented. The pathogenesis and treatment of this condition, which is rare in adults, is discussed and the literature reviewed. PMID- 1449675 TI - Multicentric glioma of the spinal cord. AB - A 24-year-old woman with neurofibromatosis presented with a 1.5-year history of pain in the neck, both shoulders and back, and a 4-month history of progressively increasing weakness of all the limbs and inability to walk. The limb weakness fluctuated and, at the height of the weakness, it was associated with hesitancy and retention of urine. Magnetic resonance imaging (MRI) showed a fusiform enlargement of the upper cervical cord with obliteration of the subarachnoid space. Imaging after gadolinium-DTPA injection revealed inhomogeneous enhancement extending from the lower medulla down to the C4 cord level, and homogeneous enhancement at D3 to D4 and D6 to D8 cord levels. The spinal cord at the lower two levels appeared morphologically normal. At operation the fusiform enlargement of the cervical cord was confirmed. The tumour was partially removed. Histology revealed it to be a fibrillary astrocytoma. PMID- 1449676 TI - Extraventricular colloid cyst. PMID- 1449677 TI - Stereotactic biopsy in AIDS patients. PMID- 1449678 TI - Transsphenoidal pituitary surgery. PMID- 1449679 TI - The odontogenic keratocyst. PMID- 1449680 TI - Roentgen ray anomalies. PMID- 1449681 TI - Benton E. Crawford radiograph of the month. Atypical root resorption. PMID- 1449682 TI - To retail or not: that's the question. PMID- 1449683 TI - Don't give your patients a chance to back out of their hygiene appointments. PMID- 1449684 TI - Assertiveness will help you deal with difficult co-workers, patients. PMID- 1449685 TI - How-to manual first step to ensure successful infection control plan. PMID- 1449686 TI - Know 'sick building' symptoms to pinpoint unexplained bills. PMID- 1449687 TI - Tinnitus suppression following cochlear implantation. A multifactorial investigation. AB - The effects of cochlear implant on loudness, annoyance, daily duration, location, and residual inhibition of tinnitus were evaluated by a closed-ended, quantifiable questionnaire in 33 postlingually deafened patients who had received implants at the University of Michigan, Ann Arbor, between 1986 and 1990. Preoperative tinnitus was present in 85% of patients. A statistical comparison of preoperative vs postoperative loudness and annoyance indicated a significant reduction in both of these complaints postoperatively. Loudness and annoyance were significantly correlated, both preoperatively and postoperatively. Fifteen patients (54%) with preoperative tinnitus demonstrated a loudness decrease of 30% or more; 43% demonstrated an annoyance decrease of 30% or more; and 48% demonstrated a decrease of 30% or more in daily tinnitus duration. Patients who experienced a loudness or annoyance decrease of 30% or more after implantation demonstrated significantly higher preoperative levels of these complaints, suggesting that degree of tinnitus reduction after implantation may be related to preoperative loudness and annoyance levels. Contralateral tinnitus suppression was reported by 42% of patients. Residual inhibition ranging from 60 seconds to several hours was reported by 50% of patients, predominantly in the ear with the implant. Age, gender, cause of hearing loss, duration of tinnitus, cochlear implant usage, and time after implantation were not predictive of tinnitus suppression. Overall, the majority of the patients (74%) thought that their cochlear implant was helpful in tinnitus suppression, especially in the ear with the implant. Contralateral residual inhibition and tinnitus suppression suggest a central mechanism contributing to these phenomena. PMID- 1449688 TI - Mechanisms of retraction pocket formation in the pediatric tympanic membrane. AB - The epidemiological nature of acquired cholesteatoma in children has shown that it occurs more often in the posterosuperior quadrant of the pars tensa and in the pars flaccida. This type of cholesteatoma is rarely seen before the age of 3 years, and serous otitis media is the most important risk factor for its occurrence. In an attempt to present a pathological rationale for these clinical findings, tympanic membranes from 11 temporal bones with purulent otitis media and 13 with serous otitis media were evaluated light microscopically and compared with 14 temporal bones without disease. Ages ranged from newborn to 3 years 6 months. The persistence of mesenchyme and greater inflammatory reaction observed in the pars flaccida and the posterosuperior quadrant of the pars tensa and changes in collagen and elastin observed in purulent otitis media and serous otitis media may represent a pathological rationale for the epidemiological nature of cholesteatoma in children. PMID- 1449689 TI - Screening audiometry using the high-risk register in a level III nursery. AB - Several factors, including those in the high-risk register, were studied in 1240 graduates of an intensive care nursery who underwent auditory brain-stem response testing. Univariate analysis, with chi 2 and Fisher's Exact Test, and stepwise logistic regression were used to identify variables associated with auditory brain-stem response outcomes. Results suggest that factors in the high-risk register do not carry equal weight and that universal screening in the intensive care nursery may be preferable. PMID- 1449690 TI - Carboplatin-radiation interaction in squamous cell carcinoma cell lines. AB - Chemoradiotherapy has been considered one of the most promising improvements in the treatment of advanced head and neck cancer. This article describes in vitro chemosensitivity to carboplatin in five squamous cell carcinoma cell lines established from head and neck cancers and in one vulvar squamous cell carcinoma cell line. Sensitivity to carboplatin was found to vary markedly when using the 96-well plate clonogenic assay and continuous drug exposure. The difference in carboplatin response between the most sensitive and the most resistant cell lines was fourfold. No cross-resistance was observed between inherent radiosensitivity and chemosensitivity. Effects of concomitant use of carboplatin and radiation were further investigated in the two cell lines that were found to be most sensitive to carboplatin. The drug was administered 1 hour before acute radiation doses, and an additive effect was observed in both cell lines. PMID- 1449691 TI - Analysis of laryngeal movement by digital subtraction laryngography. AB - Fine movement of laryngeal components was analyzed by digital subtraction laryngography with the use of a digital fluorography system. Two kinds of image processing modes, the super pulse image subtraction mode and the time interval difference mode, were used for this purpose. By the super pulse image mode, the distance and extent of movement of laryngeal components at vocal initiation and during phonation could be observed. By the time interval difference mode, the amount and direction of motion for a certain interval and fine movement, such as vocal initiation, were determined. PMID- 1449692 TI - Cytogenetic alterations in laryngeal carcinomas. AB - The purpose of this study was to determine the most frequent chromosomal abnormalities in laryngeal carcinomas. Biopsy specimens of surgical resections from laryngeal squamous cell carcinomas from 15 patients representing different degrees of histologic differentiation were analyzed in short-term culture. Nine of the 15 tumors were hypodiploid with 41 to 45 chromosomes, and four of the 15 tumors were polyploid with more than 50 chromosomes. The most frequent chromosomal alterations we noted included deletion of the short arm of chromosome 3 in 60%, monosomy of chromosome 11 in 30%, and inversions of chromosome 9 and 16 that were present in 20% of the cases. PMID- 1449693 TI - Should granulomas be excised in children with long-term tracheotomy? AB - We reviewed 265 rigid bronchoscopies performed in 50 children with tracheotomy dependent subglottic stenosis (25 congenital, 25 acquired). Granulomas developed in 40 children (80%) and were unrelated to age, sex, race, gastroesophageal reflux, tracheotomy duration, or type of stenosis. The incidence of small to medium, large, and obstructing granulomas at endoscopy was 28%, 6%, and 0%, respectively. Compared with a baseline finding of no granuloma at preceding bronchoscopy, the odds of granuloma recurrence were 3.0 after an unexcised granuloma (95% confidence interval [CI], 1.1 to 8.4), 4.1 after granuloma excision (95% CI, 1.4 to 11.9), and 7.3 after expansion surgery (95% CI, 1.1 to 49.2). Considering the low incidence of large or obstructing granulomas, and the failure of granuloma excision to diminish recurrence, we do not recommend interval excision of nonobstructing granulomas in children with stable tracheotomies. PMID- 1449694 TI - Postoperative technetium scanning in patients with submandibular duct diversion. AB - Submandibular duct diversion is a common procedure for refractory sialorrhea in children. The procedure reroutes Wharton's ducts from the floor of the mouth to the tongue base. As the majority of saliva in the resting state is produced by the submandibular glands, rerouting markedly decreases sialorrhea. However, the procedure has been criticized in that diversion may cause fibrosis and stricture of the ducts. The gland would atrophy, and the physiologic functions of saliva would be lost. Glandular function of six patients with cerebral palsy (mean age, 14.7 years) was evaluated by technetium scanning (mean time after surgery, 43 months). Four patients had normal bilateral function; two patients had no function in one gland but normal function in the contralateral gland. We conclude that bilateral submandibular duct diversion maintains long-term function in at least one gland. PMID- 1449695 TI - Needle-wire localization of an infratemporal fossa foreign body using computed tomography. AB - We report a case involving the localization and surgical removal of a traumatically introduced foreign body deep within the infratemporal fossa. Needle hookwire placement with computed tomographic guidance allowed the precise localization and marking of the foreign body. Surgical removal under local anesthesia and without extensive exploration was, therefore, possible. The details of the localization and marking techniques are described. Needle-hookwire localization under computed tomographic guidance should be considered for deeply located foreign bodies in the head and neck area. PMID- 1449696 TI - Primary carcinoid tumors of the middle ear. Report on four cases and a review of the literature. AB - Carcinoid tumors are rare in the middle ear. To our knowledge, only 17 cases could be found in the literature, the first of which was described in 1980. In addition to enlarging on a previous observation we present three new cases. The neoplasms showed a striking, heterogeneous aspect ranging from solid trabecular to tubuloglandular growth patterns resembling the classic carcinoid tumor and adenomatous middle ear tumor, respectively. Based on immunohistochemistry and electron microscopy, three cell types were found. A review was made of our four patients and the cases described in the literature. The medical histories ranged from 1 month to 9 years. Presenting symptoms and signs were not characteristics, but hearing loss predominated. In two patients, the eardrums were perforated, in all the others it was intact and often bulging. Surgery, usually radical mastoidectomy, was performed in all cases. Often the tumor encased the ossicular chain, without infiltration. In two patients, local recurrence occurred that was treated successfully with surgery. All the cases showed an indolent biological course and the tumors were clinically nonfunctional, despite the recognition of biogenically active products by immunohistochemistry. To our knowledge, regional or distant metastases have never been reported. Conservative surgery with radical removal of the primary or recurrent tumor is the treatment of choice. PMID- 1449697 TI - Transoral surgical management of lesions of the base of the tongue. AB - Lesions of the base of the tongue are rare in the pediatric population. However, when present these lesions may lead to airway obstruction and feeding difficulties. Two patients with lesions of the base of the tongue are described to demonstrate the diagnosis and management of this difficult clinical problem. The use of a transoral median glossotomy for total excision of these lesions is advised in this article. This approach affords excellent surgical exposure, early return to a normal diet, and lack of facial scars. PMID- 1449698 TI - Pathologic quiz case 2. Abscess with sulfur granules with organisms consistent with Actinomyces species. PMID- 1449699 TI - Pathologic quiz case 1. Nasal sarcoidosis. PMID- 1449700 TI - Rhinoplasty surgery. PMID- 1449701 TI - Surgery vs chemotherapy. PMID- 1449702 TI - Electrodissection tonsillectomy. PMID- 1449703 TI - Dolichol: a curriculum cognitionis. AB - Dolichols were first described about 30 years ago when animal tissues were being examined for the presence of a putative precursor to the polyisoprenoid side chain of ubiquinone. These long-chain 2,3-dihydro-polycis-isoprenoid alcohols are found in all eukaryotic organisms. In many plant tissues they are accompanied by families of other polyisoprenoid alcohols that are usually similar molecules and possess an unsaturated alpha-isoprene residue. Analogy with the role of bactoprenyl phosphates in the synthesis of bacterial wall glycans led to the discovery that the mono- and di-phosphates of dolichols function as cofactors in protein N-glycosylation, involving the formation of glycosylated derivatives of dolichol as intermediates. Variation of the concentration of dolichyl phosphate was shown to be one way of controlling protein N-glycosylation. This can be achieved by modification of the relative activities of dolichol kinase and dolichol phosphate phosphatase. Modulation of the biosynthetic pathway, still not fully understood, of dolichyl phosphate may also be an important factor. Several disease conditions involve aberrations in these pathways. PMID- 1449704 TI - Dolichol: function, metabolism, and accumulation in human tissues. AB - Dolichol, a homologous series of alpha-saturated polyisoprenoid alcohols containing 14-24 isoprene units, was first isolated and characterized about 30 years ago. The phosphorylated form, dolichyl phosphate, is required for the biosynthesis of biologically important N-linked glycoproteins. Dolichol itself is synthesized by a common isoprenoid pathway from acetate and synthesis can be inhibited by some of the factors that inhibit cholesterol biosynthesis. It is metabolized very slowly and accumulates in tissues during aging and in certain lipid storage diseases. Dolichyl phosphate and cholesterol also accumulate in tissues during aging, but to a lesser extent than dolichol. Although dolichol and cholesterol have important metabolic functions, their accumulation in tissues can have deleterious effects. PMID- 1449705 TI - Dolichol metabolism in Chinese hamster ovary cells. AB - The addition of oligosaccharide to asparagine residues of soluble and membrane associated proteins in eukaryotic cells involves a polyisoprenoid lipid carrier, dolichol. In Chinese hamster ovary cells, the major isomer of this polyisoprenol has 19 isoprenyl units, the terminal one being saturated. Our laboratory has developed a procedure to analyze the levels and nature of the cell's dolichyl derivatives. Chinese hamster ovary cells contain predominately activated, anionic dolichol derivatives, such as oligosaccharyl pyrophosphoryldolichol, monoglycosylated phosphoryldolichols, and dolichyl phosphate. Our studies show that in growing cells there is continual synthesis of total dolichol. Also, preliminary data suggest there is no catabolism or secretion of this lipid. The level of dolichyl phosphate did not change significantly under a variety of conditions where the levels of enzyme activities utilizing dolichyl phosphate did change. These results suggested that these enzymes had access to the same pool of dolichyl phosphate and had similar Km values for this lipid. PMID- 1449706 TI - The importance of N-linked glycoproteins and dolichyl phosphate synthesis for fusion of L6 myoblasts. AB - Myoblasts fuse to form multinucleated myotubes, one of the early steps in the formation of multinucleated muscle fiber. The fusion reaction is accompanied by biochemical differentiation resulting in the expression of a variety of enzyme activities and macromolecules, particularly creatine phosphokinase. The fusing myoblast is thus an excellent system for use in studies on the molecular basis of cellular recognition. This report focuses on the role played by glycoproteins in this process. It was found that alteration of cell-surface glycoproteins, using oligosaccharide-processing inhibitors that interfered with the synthesis of the high-mannose type of N-linked oligosaccharide, resulted in the inhibition of both the fusion reaction and biochemical differentiation as determined by measurement of creatine phosphokinase. Ketoconazole, compactin, and lovastatin, which affect dolichol and cholesterol biosynthesis, were also potent fusion inhibitors. These observations, coupled with earlier studies on the characterization of fusion defective myoblast cell lines defective in glycoprotein biosynthesis, point to the importance of surface glycoproteins in cellular recognition in L6 myoblasts. PMID- 1449707 TI - Ubiquinone, dolichol, and cholesterol metabolism in aging and Alzheimer's disease. AB - The lipid compositions of various regions of the human brain were investigated during aging and in Alzheimer's disease. The phospholipid amounts and compositions remained unchanged during aging. There were, however, considerable differences both in phospholipid composition and amount when the various regions were compared. The level of dolichol increased severalfold in all regions up to the age of 70, but there was no further elevation thereafter. The ubiquinone level decreased significantly in all parts of the brain upon aging. In Alzheimer's disease, the dolichol level was decreased in all regions, and particularly, in those affected by the disease. In contrast, the dolichyl-P concentration increased in those regions that exhibited morphological changes. There was no modification in cholesterol distribution, but a significant elevation in ubiquinone content was observed in most regions. The only phospholipid whose level was elevated was phosphatidylinositol, and only in those parts of the brain that were affected. The content of polyunsaturated fatty acids in phosphatidylethanolamine was greatly decreased in connection with the disease, with a parallel increase in the saturated portion. The results indicate that Alzheimer's disease results in specific and significant changes in the levels of lipid products of the mevalonate pathway in the brain. PMID- 1449709 TI - The occurrence of long chain polyprenols in leaves of plants of Rosaceae family and their isolation by time-extended liquid chromatography. AB - The long chain polyprenols composed of 30 and more isoprene units from leaves of plants belonging to the genera Potentilla and Rosa have been described. They occur in the form of fatty acid esters. The composition of polyprenol mixture was species dependent and its content reached ca. 0.5% wet weight. Large scale preparation of individual polyprenols from a natural polyprenol mixture was performed using time-extended liquid chromatography on the hydrophobic gel Lipidex-5000. PMID- 1449708 TI - New developments in the synthesis of phosphopolyprenols and their glycosyl esters. AB - Efficient methods were developed in our group in recent years for chemical synthesis of polyprenyl phosphates, polyprenyl monophosphate sugars, and polyprenyl diphosphate sugars, which were known to serve as important intermediates in biosynthesis of complex carbohydrates. A simple procedure was developed involving the phosphorylation of aliphatic alcohols with tetra-n butylammonium dihydrogen phosphate and trichloroacetonitrile. Monophosphates of various natural and modified dolichols and polyprenols, as well as the derivatives of retinol, cholesterol, and nonacosanol, were prepared in high yields. First syntheses of dolichyl thiophosphate and dolichyl hydrogen phosphonate were developed, and these derivatives were of interest as analogs of dolichyl phosphate. Polyprenyl monophosphate sugars, including derivatives of alpha- and beta-anomers of D-glucopyranose, D-galactopyranose, D-mannopyranose, and 2-acetamido-2-deoxy-D-glucopyranose, were obtained smoothly from moraprenyl trichloroacetimidate and acylated glycosyl phosphates after deprotection. A method for the synthesis of polyprenyl diphosphate sugars from polyprenyl phosphoroimidazolidate and unprotected glycosyl phosphates was shown to be applicable for a wide range of the monosaccharide derivatives including hexoses, deoxyhexoses, 2-acetamido-2-deoxyhexoses, and uronic acids. A series of the oligosaccharide derivatives was also prepared by this method. PMID- 1449711 TI - Changes of dolichol and dolichyl fatty acyl esters during the germination and development of soybeans. AB - The amounts of dolichol and dolichyl fatty acyl esters and their composition in various parts of soybean seedlings were determined during germination and development. The dolichol content of cotyledons decreased during germination. Dolichyl fatty acyl esters were identified in cotyledons and the amount was estimated by high performance liquid chromatography. The relative amounts of short-chain dolichols of 15, 16, and 17 isoprene units increased during development of the seedlings. The homologue distribution of free dolichol was different from that of dolichyl fatty acyl esters. The relative amounts of dolichols with 16, 17, and 18 isoprene units were greater in free dolichol than in dolichyl fatty acyl esters. The percentages of long-chain saturated fatty acids in dolichyl fatty acyl esters, specifically 21:0, 22:0, 23:0, 24:0, and 25:0, increased during development. These fatty acids represented more than 40% of the fatty acids in dolichyl fatty acyl esters in stems. These results suggest that dolichyl fatty acyl esters are not a storage form of dolichol. The large accumulation of dolichol and dolichyl fatty acyl esters in the leaves, where photosynthesis takes place, suggests some other function. PMID- 1449710 TI - Yeast dolichyl-phosphomannose synthase: reconstitution of enzyme activity with phospholipids. AB - The activity of purified recombinant yeast dolichyl-phosphomannose synthase (EC 2.4.1.83) was assessed following reconstitution of the enzyme with phospholipids. The yeast synthase, similar to the mammalian enzyme, was active when reconstituted with phosphatidylethanolamine dispersions but had little (less than 5%) activity in stable phosphatidylcholine bilayers. The enzyme was activated by adding increasing amounts of diacylglycerol to phospholipid bilayers, suggesting that activity of the yeast enzyme was dependent on lipid phase properties rather than specific phospholipids. The synthase could also be reconstituted as an active enzyme in bilayers prepared with a commercial crude lipid preparation containing 40% phosphatidylcholine, but at a rate 10% of that occurring in phosphatidylethanolamine. Vesicles composed of the 40% phosphatidylcholine lipid mixture, dolichyl phosphate, and enzyme were leaky in the presence of divalent cations, and dolichyl-phosphomannose synthase did not appear to catalyze the translocation of dolichyl phosphomannose across membranes at a catalytically significant rate under the assay conditions employed. PMID- 1449712 TI - A dolichol acyltransferase present in rat and human postheparin plasma. AB - Incubation of small unilamellar vesicles consisting of dioleoyl phosphatidylcholine-dioleoyl phosphatidylethanolamine (3:1) and 2 mol% [3H]dolichol-19 with postheparin plasma from rat resulted in the formation of dolichyl oleate. Normal plasma or heat-treated postheparin plasma contained no activity and, hence, the results indicate the presence of a cell surface associated dolichol acyltransferase that can be released into the blood by heparin. The reaction is strongly stimulated by phosphatidylethanolamine and Ca2+, whereas no stimulation with triglycerides or acyl-CoA was observed. Together with the fact that the only product formed was dolichyl oleate, these results strongly suggest that a transacylation mechanism from the phospholipids to dolichol is operative in the liposomes. Gel chromatography of postheparin plasma yielded a molecular mass of about 350 kilodaltons for the active enzyme and density gradient centrifugation indicated that this high molecular mass complex consists mainly of proteins. Finally, we conclude that this enzyme is not unique to the rat, but is also present in human postheparin plasma. PMID- 1449713 TI - Uptake of dolichol by Vero cells. AB - Characterization and kinetics of dolichol uptake by a Vero cell line are reported. Vero cells incorporate dolichol in a time- and dose-dependent manner. Optimal uptake is found at 37 degrees C and at a pH of 7.4. In contrast to cholesterol, an inhibitory effect on the dolichol incorporation is found for farnesol, geraniol, and retinol. Long chain polyprenols were slightly stimulatory. The translocation seems not to be highly energy dependent. The lack of substantial inhibition by chloroquine does not plead for a receptor-mediated endocytosis. Incorporated dolichol was distributed over both membranes and supernatant fractions, paralleling the distribution of the lysosomal marker beta N-acetylhexosaminidase. The incorporated dolichol is subject to a fast efflux process, which is potentiated by the presence of lipid acceptors in the extracellular medium. PMID- 1449714 TI - Blood dolichol in lysosomal diseases. AB - Highly elevated serum total dolichol (free dolichol + dolichyl ester) concentrations have recently been found in two lysosomal storage diseases, aspartylglucosaminuria (AGU) and mannosidosis. The present study demonstrates that the increase of serum dolichol in AGU patients is caused by an increase of serum free dolichol. In 15 patients the mean serum level of free dolichol (227 +/ 16 ng/mL) was 1.9 times higher (p < 0.001) than that in healthy controls (120 +/ 6 ng/mL), while the amounts of dolichol fatty acid esters were similar in the patients and controls (110 +/- 9 vs. 118 +/- 6 ng/mL). In contrast, 10 patients with neuronal ceroid-lipofuscinosis (NCL) (three with infantile, four with juvenile, and three with variant late infantile NCL) had significantly (p < 0.01) lower mean serum levels of both free (79 +/- 5 ng/mL) and total (159 +/- 6 ng/mL) dolichol than age-adjusted healthy controls (free, 100 +/- 6 ng/mL; total, 206 +/ 14 ng/mL). Decreased blood dolichol has not been reported earlier for any other disease. We conclude that the increased serum free dolichol in AGU reflects disturbed lysosomal function and that the decreased free and esterified dolichols in NCLs speak against their presumed primary lysosomal nature. PMID- 1449715 TI - Rat liver lysosome membranes are enriched in alpha-tocopherol. AB - The subcellular distribution of alpha-tocopherol has been studied in rat liver. Lysosomal membranes were found to be considerably enriched in alpha-tocopherol with 6300 pmol/mg membrane protein, whereas mitochondrial membranes and microsomes contained 530 and 200 pmol/mg membrane protein, respectively. The 37 fold higher specific content of alpha-tocopherol in lysosomal membranes relative to homogenate indicates that lysosomes could be a target of cellular pathology in vitamin E deficiency states. PMID- 1449716 TI - Protein-linked isoprenoid lipids in dexamethasone-treated human lymphoid lines in culture. AB - Accumulation of isoprenoids was studied in two cell lines derived from acute T cell leukemia: CEM-C7 cells, whose growth is inhibited by the glucocorticoid dexamethasone, and CEM-C1 cells, which are resistant to this steroid. Isoprenoids were measured by growing the cells in serum-free medium in the presence of lovastatin, which blocks synthesis of mevalonate, and then labeling with exogenous [3H]mevalonolactone. In both cell lines, isoprenoids associated with proteins were detected in cytoplasm, nucleus, and chromatin, and in the chromatin residue that remains after extraction of histone and nonhistone proteins. Differences in labeling were detected after treatment with dexamethasone in the CEM-C7 line, showing a decrease in the cytoplasmic fraction with a corresponding increase in both the nuclear and chromatin fractions as compared with untreated cells. No change was seen in the CEM-C1 line. In both cell lines, 25-30% of the incorporated label was released by treatment with acid or alkali. However, the majority of the label required treatment with methyl iodide for the release of organic-soluble tritiated products. After extraction with chloroform, the lipid fractions contained farnesol, geraniol, dolichols, and possibly nerolidol. PMID- 1449717 TI - Localization and preferred orientations of ubiquinone homologs in model bilayers. AB - The localization of ubiquinone has been investigated in phospholipid bilayer vesicles in studies of fluorescence quenching of membrane-bound probes by ubiquinone homologs (Qn, where n is the number of the isoprenoid units of the chain). Fluorescence-quenching data obtained by using a set of anthroylstearate probes, having the fluorophore located at different depths, revealed that ubiquinone-3 is located throughout the whole bilayer thickness. From the bimolecular quenching constants in the membrane, lateral diffusion coefficients in two dimensions were calculated to span values of 10(-7)-10(-6) cm2.s-1. This suggests that ubiquinones laterally diffuse in a very fluid environment. On this basis, it is proposed that their translational diffusion in the bilayer takes place in two dimensions, with the quinone ring oscillating between the two bilayer surfaces within a hydrophobic environment not extending beyond the glycerol region. This model implies that the quinonic head is both settled near the polar surface of the bilayer and buried into the host hydrocarbon interior. This two-site distribution was confirmed for all Qn, except Q0, by their linear dichroism spectra in the bilayers provided by disc-like lyotropic nematic liquid crystals. These spectra also provided detailed information on the preferential orientations of the quinonic head of the different derivatives within the two sites. The mechanism by which the localization and orientation of Qn guest molecules inside the host bilayer is modulated by the isoprenoid chain length is discussed on a thermodynamical basis. Being that Qn is expected to be also widely contained in the highly curved cristae of the mitochondrial inner membrane, by using rod-like lyotropic nematic liquid crystals we searched out effects of the curvature of the host bilayer on those Qn distributions. The linear dichroism measurements reveal that Qn guest molecules are no longer obliged to find a partition between two different types of localizations when the host bilayer is highly curved. In this case all Qn, even the longest Q10, were found to stay parallel to the amphiphilic chains with a single site localization of the head near the polar interface. By the same linear dichroism technique, the local ordering of all Qn derivatives was also evaluated. The order parameters were found to be basically the same for all derivatives. This result is justified on the basis of the relaxation, caused by the surface curvature, of the lateral compression of the host chains. PMID- 1449718 TI - Dolichyl-pyrophosphoryloligosaccharide protein oligosaccharide transferase in neuronal ceroid-lipofuscinosis. AB - The kinetics of the oligosaccharide transfer from oligosaccharyl pyrophosphoryldolichol to endogenous protein acceptors in human fibroblasts were studied. No alterations in the transferase activity and enzyme characteristics could be observed in fibroblasts from neuronal ceroid-lipofuscinosis (NCL) patients. Analysis of urinary dolichol of two NCL patients also did not reveal substantial differences with respect to controls. PMID- 1449719 TI - Partition of free dolichol in human urine. AB - We have demonstrated that dolichol is present in the urinary supernatant. Most of the dolichol present in the supernatant seems to be associated with cellular debris or membrane fragments. The amount of sediment in healthy subjects correlate well with the volume of urine. Although it is illogical to express urinary dolichol relative to urine volume, a good correlation between the amount of sediment and urine volume has made its use justifiable. Because of the presence of a substantial amount of dolichol in the supernatant, it seems better to use uncentrifuged whole urine as the sample for measurement of dolichol. PMID- 1449720 TI - Particulate glycogen of mammalian liver: specificity in binding phosphorylase and glycogen synthase. AB - The glycogen particle - glycogen metabolizing enzyme complex was investigated to gain some understanding of its physiological significance. Fractionations of populations of particles from mouse liver were carried out utilising open column and high performance liquid chromatography, and based either on the molecular weight of the particles or the hydrophobic interactions of the glycogen associated proteins. The activities of glycogen phosphorylase and glycogen synthase were measured in these fractions. Fractionations were of tissue in different stages of glycogen deposition or mobilization. In animals fed ad libitum, glycogen synthase was associated with the whole spectrum of molecular weights, while the glycogen phosphorylase distribution was skewed in favour of the lower molecular weight species. Under conditions of glycogen mobilization, the phosphorylase distribution changed to include all molecular weights. The hydrophobic interaction separations demonstrated that glycogen synthase binds to a specific subpopulation of particles that is a minor proportion of the total. In general, there was a direct relationship of the total amount of phosphorylase and synthase bound during periods of mobilization and deposition, respectively. Two notable exceptions were the large amounts of glucose-6-P dependent synthase present during the early period of glycogen mobilization and the high amounts of active phosphorylase appearing shortly after food withdrawal, in spite of interim glycogen deposition from presumably already ingested food. PMID- 1449721 TI - Modification of mRNA-associated proteins during changes in growth conditions. AB - Following serum stimulation of quiescent 3T6 cells, an elevated in vivo rate of translation was observed. These studies were designed to identify the proteins associated with polysomal mRNA under different growth conditions in an attempt to establish a relationship between translational rate and the mRNA-associated proteins. Ultraviolet cross-linking of proteins to mRNA was employed to ensure that only genuine mRNA-associated proteins were investigated. Our results revealed little change in the population of mRNA-binding proteins, although minor variations in the synthesis of several proteins, most notably a 32 kilodalton species, were observed during growth transitions. These investigations demonstrate further that most of the mRNA-binding proteins were phosphorylated with the degree of phosphorylation of several proteins influenced by growth conditions. PMID- 1449722 TI - Hepatic heparan sulphate proteoglycan and the recycling of transferrin. AB - Heparan sulphate proteoglycan, labelled with [35S]sulphate, was prepared from rat livers for studies of its interaction with purified rat transferrin. Affinity chromatography of the preparation on columns of immobilized differic transferrin and apotransferrin showed that the proteoglycan possessed affinity for both types of matrices at pH 7.3 and that this affinity significantly increased at pH 5.6. The glycosaminoglycan chains liberated from the proteoglycan by heparan sulphate lyase also bound to apotransferrin, albeit less strongly, whereas the deglycosylated core protein exhibited virtually no interaction with this matrix. In the presence of the proteoglycan at pH 5.6, the release of iron from the N lobe of transferrin was accelerated. These observations suggest that heparan sulphate proteoglycan from the liver can mimick some of the known functions of bona fide transferrin receptors and, hence, interaction with the proteoglycan may provide an alternative nondegradative pathway for transferrin through hepatic cells. PMID- 1449723 TI - Proliferation is required for induction of terminal differentiation of Friend erythroleukemia cells. AB - The relationship between cell proliferation and differentiation has long been a source of controversy. Stimulation of normal erythroid maturation results in a finite number of cell divisions accompanied by a concomitant accumulation of hemoglobin. Friend erythroleukemia cells treated with hexamethylene bisacetamide differentiate in a similar manner, while agents such as hemin apparently induce differentiation without limiting cell proliferation. Aphidicolin, an inhibitor of DNA synthesis, has been reported to induce differentiation in the absence of cell proliferation. Using these three chemicals we have investigated the relationship between cell proliferation and erythrocytic maturation by exposing Friend erythroleukemia cells to either hexamethylene bisacetamide (5 mM), hemin (100 microM), or aphidicolin 1.2 microM) and examining the effects on cell growth, morphology, and hemoglobin production. Proliferation in the presence of hexamethylene bisacetamide is limited to four to five rounds of cell division, while hemin has no inhibitory effect. Hexamethylene bisacetamide initiates the complete erythrocytic maturation program, including cellular structural changes and hemoglobin synthesis. Hemin stimulates only globin gene transcription, not differentiation. Aphidicolin inhibits cell growth within 24 h, but does not induce differentiation. Furthermore, inhibition of proliferation by aphidicolin prevents subsequent hexamethylene bisacetamide induced differentiation. These results indicate that at least one round of cell division is required for initiation of erythrocytic differentiation. PMID- 1449724 TI - Secretion of SPARC by endothelial cells transformed by polyoma middle T oncogene inhibits the growth of normal endothelial cells in vitro. AB - Endothelioma cells expressing the polyoma virus middle T oncogene induced hemangiomas in mice by the recruitment of nonproliferating endothelial cells from host blood vessels (Williams et al. 1989). I now report that SPARC, a Ca(2+) binding glycoprotein that perturbs cell-matrix interactions and inhibits the endothelial cell cycle, is produced by endothelioma cells and is in part responsible for the alterations in the morphology and growth that occur when nontransformed bovine aortic endothelial cells are cocultured with endothelioma cells. Normal endothelial cells cocultured with two different middle T-positive endothelial cell lines, termed End cells, exhibited changes in shape that were accompanied by the formation of cell clusters. Media conditioned by End cells repressed proliferation of normal endothelial cells, but enhanced that of an established line of murine capillary endothelium. Radiolabeling studies revealed no apparent differences in the profile of proteins secreted by aortic or capillary cells cultured in End cell conditioned media. Characterization of proteins produced by End cells led to the identification of type IV collagen, laminin, entactin, and SPARC as major secreted products. Although SPARC did not affect the morphology of End or capillary cells, it was associated with overt changes in the shape of aortic endothelial cells. Moreover, SPARC and a synthetic peptide from SPARC domain II inhibited the incorporation of [3H]thymidine by aortic cells, but had minimal to no effect on the capillary endothelial cell line. The inhibition of growth exhibited by aortic endothelial cells cultured in End cell conditioned media could be partially reversed by antibodies specific for SPARC and SPARC peptides. These studies indicate a potential role for SPARC in the generation of hemangiomas by End cells in vivo, a process that requires normal (host) endothelial cells to disengage from the extracellular matrix, withdraw from the cell cycle, migrate, and reassociate into the disorganized cellular networks that comprise cavernous and capillary hemangiomas. PMID- 1449725 TI - Increased preproenkephalin A gene expression in the rat heart after induction of a myocardial infarction. AB - The expression of preproenkephalin A (ppENK) gene was investigated in the rat heart, following the onset of myocardial infarction induced by ligation of the left anterior descending coronary artery. The relative abundance of ppENK mRNA and the level of enkephalins were measured by Northern blot analysis and radioimmunoassay, respectively, in the ventricles from control-unoperated, sham operated, and operated rats. Three hours after the surgery, a comparison between rats with infarction and sham-operated rats revealed that the relative abundance of ppENK mRNA and the level of enkephalins were increased three- to four- and two to three-fold, respectively, in the ventricles of rats with infarction. No difference was observed between rats with infarction and sham-operated rats 24 h after the surgery, or between rats with infarction compared at time intervals of 3 and 24 h following the surgery. The abundance of the ppENK mRNA in the polysomal fraction of the ventricular septum was also measured 3 h after the surgery and found to be threefold higher in rats with infarction as compared with sham-operated rats. These results indicate that the level of enkephalins rapidly increases in the ventricles of rats following myocardial infarction, and that this higher level may be ascribed to a stimulation of the local synthesis of enkephalins. PMID- 1449726 TI - Accelerated entry of aortic smooth muscle cells from spontaneously hypertensive rats into the S phase of the cell cycle. AB - The present study was designed to characterize the growth kinetics of the exaggerated proliferative response to mitogens of vascular smooth muscle cells from spontaneously hypertensive rats compared with cells from normotensive Wistar Kyoto controls. Cellular DNA content, analyzed by flow cytometry, demonstrated a 4-h accelerated entry into the S phase of the cell cycle of vascular smooth muscle cells from spontaneously hypertensive rats; the significant (4.5-fold) increase in the percentage of cells in the S phase occurred between 8 and 12 h after calf serum stimulation. A 3.9-fold increase of cells in the S phase was seen in the normotensive controls only between 12 and 16 h. Transit through the cell cycle was quantitated by flow cytometry using the Hoechst 33,342- bromodeoxyuridine substitution technique. Vascular smooth muscle cells from spontaneously hypertensive rats went through the cell cycle 4 h ahead of cells from normotensive Wistar-Kyoto rats. This accelerated transit of spontaneously hypertensive rat cells was mostly due to an earlier entry into the S phase. Persistence of this new intermediate phenotype in cell culture suggests its primary pathogenetic role in spontaneous hypertension. PMID- 1449727 TI - Transport of Ca2+ by diltiazem across the lipid bilayer in model liposomes. AB - The calcium channel antagonist diltiazem was examined for its ability to translocate Ca2+ from an aqueous medium to the nonpolar lipid milieu. We monitored the spectral changes caused by the drug-mediated cation transport at 37 degrees C in unilamellar vesicles made of dimyristoyl phosphatidylcholine (DMPC) and containing the calcium-sensitive dye arsenazo III trapped inside. Vesicle leakage or membrane fusion caused by diltiazem was assessed by the use of vesicles containing fluorescent indicators. These effects were, however, found to be insignificant compared with ion transport. The transport was negligible at temperatures below the liquid crystalline to gel transition temperature of DMPC indicating a carrier mechanism of ion transport. A quantitative analysis of the transport kinetics indicated that a 1:2 Ca(2+)-drug complex is formed inside the lipid. The calcium ionophoretic ability of diltiazem, combined with other related data, suggests a possible role for Ca2+ in the conformation of the drug in the lipid membrane milieu and in its interaction with the calcium channel. PMID- 1449728 TI - Effects of nonenzymatic glycation of subfragment-1 of myosin on interactions with actin. AB - Nonenzymatic bonding of reducing sugars to subfragment-1 of myosin (S-1) resulted in a reduction in actin-activated S-1 ATPase activity. Fructose caused a greater reduction than glucose. The Km for binding of actin to S-1 was significantly increased with sugar derivatization. In addition, sugar derivatization lowered the ability of S-1 to promote polymerization of G-actin. Western blot analysis demonstrated that glucose was nonenzymatically incorporated into the 50 and 20 kilodalton (kDa) fragments of S-1 with preponderance in the 20-kDa fragment. The reduced affinity of derivatized myosin for actin is indicated by the increased Km, the reduced ability to stimulate actin polymerization, and the positive Western blot reaction in the 20-kDa fragment. PMID- 1449729 TI - Assessment of basic cognitive abilities in relation to cognitive deficits. AB - A modal model of information-processing was used to select a battery of nine tasks of basic cognitive ability (learning, relearning, reaction time, probe recall, Sternberg search, self-paced probe, stimulus discrimination, tachistoscopic full report, tachistoscopic partial report). Parameters from these tasks operationalized the model. After extensive pilot testing of the tasks to establish reliability, we tested 40 subjects (20 with mental retardation and 20 college students) on all tasks and the WAIS-R. The parameters from the tasks were generally reliable (.7 through .9) and had low correlations with IQ (average about .37). Nearly all of the major cognitive parameters differentiated significantly between groups. A subset of the basic cognitive parameters predicted IQ with an estimated multiple correlation in the general population of .72. Prediction of IQ using basic cognitive parameters was better for subjects with mental retardation than for college students. A modified version of the modal model was supported. Results show that individual differences in higher mental processes are highly dependent on basic cognitive abilities and can be predicted from them. These findings have substantial implications for the development of models of information-processing. PMID- 1449730 TI - Teaching self-instruction utilizing multiple exemplars to produce generalized problem-solving among individuals with severe mental retardation. AB - Four residents of a group home who had severe mental retardation were taught to use self-instruction in combination with multiple exemplars to solve task-related problems. The combined strategy was associated with generalization to untrained problems as well as response maintenance of the problem-solving strategy (i.e., responding to multiple exemplars and self-instructing). The use of the strategy was discussed in terms of instructional strategies for teaching self-instruction and areas for future research, including isolating the factors responsible for generalization and identifying the role of language in promoting generalized responding. PMID- 1449731 TI - Families of children with mental retardation: comprehensive view from an epidemiologic perspective. AB - Data covering a 15-year period on the health, behavior, and functioning of a representative population of families of children with mental retardation and comparison children were used in cluster analysis to obtain relatively homogeneous groupings of families. Only a small minority of families of children with mental retardation did not cluster together with comparison families. More than a third functioned well and had a middle-class orientation; less than a third functioned poorly. A few clusters had ambiguous configurations, but most were easily understood and conformed generally to expectations in validation analyses. PMID- 1449732 TI - General slowing of information-processing by persons with mental retardation. AB - On measures of speeded performance, persons with mental retardation typically respond more slowly than do those without mental retardation. A review of 45 published studies yielded 518 pairs of response times (RTs) in which each pair consisted of a mean RT for a group of persons with mental retardation for an experimental condition and the corresponding mean RT for a group of persons without mental retardation. The primary result was that RTs of individuals with mental retardation increased linearly as a function of RTs for persons without mental retardation in corresponding conditions. These results are consistent with the view that differences in processing speed between persons with and without mental retardation reflect some general (i.e., nontask specific) component of cognitive processing. Possible candidates for the general component were discussed. PMID- 1449733 TI - Sentence processing by adolescents with and without mental retardation. AB - A more thorough test of the hypothesis that persons with mental retardation are less likely to construct semantically integrated representations of sentences that they hear than are subjects without mental retardation (Merrill & Bilsky, 1989; Merrill & Mar, 1987) was provided. A series of sentences were presented to adolescents with and without mental retardation. Their memory for the object nouns of the sentences was then tested when they were provided with either the subject noun, the verb, or the subject plus verb of the sentence as a retrieval cue. The two-word cue was relatively better if an integrated semantic representation was constructed. Manipulations included decreasing the processing time given to subjects (expected to inhibit the construction of integrated representations) and presenting a picture with the sentence (expected to facilitate the construction of integrated representations). The reduction in time decreased performance for the subjects without mental retardation to the level normally observed for those with mental retardation; presenting a picture increased performance of subjects with mental retardation to the level of comparison subjects. Results support the suggestion that previously observed differences in sentence processing between individuals with and without mental retardation may be due to differences in generating integrated representations of the sentences during processing. PMID- 1449734 TI - Association between gastrostomy and death: cause or effect? PMID- 1449735 TI - [Exarticulation and replantation of 11, 21]. PMID- 1449736 TI - [Occlusive treatment of atrophic and erosive oral lichen planus with Clobetasol Propionate 0.05% ointment (Dermovat)]. AB - The treatment of eight patients with histologically verified atrophic or erosive lichen planus are reported. The lesions of WHO-diagnosis code 697.02 were subdivided into three classes: atrophic, minor erosive and major erosive. Clobetasol Propionate ointment was placed in the buccal mucosa under an occlusive DuodermR dressing. Healing with striation was obtained in all of those lesions classified as atrophic or minor erosive, while major erosive lesions showed improvement, but persisted. PMID- 1449737 TI - [Exarticulation 11, luxation 21, 9-year old boy patient]. PMID- 1449738 TI - [Caries in 2-3 year old children in relation to feeding habits and nationality]. PMID- 1449739 TI - [Chemo-mechanical excavation with Caridex system--an alternative]. PMID- 1449740 TI - [Inlays of plastic, glass or porcelain]. PMID- 1449741 TI - [Pulp tester]. PMID- 1449742 TI - [Medical protective gloves in dental practice]. PMID- 1449743 TI - [Quality assurance in health service]. PMID- 1449744 TI - [Fracture induced constriction treated by Continuous Passive Motion (CPM)]. AB - Aspects of the history of treatment of painful joints are commented upon. It is pointed out, that the medical and dental professions have for more than 125 years been aware, that immobilization of joints may have harmful effects. Still, research on therapeutic motion of painful joints dates back only 25 years. A case is reported of fracture associated constriction, possibly due to secondary involvement of the temporalis muscle and especially its tendineous insertion on the muscular process of the mandible. When the patient was treated with the CPM apparatus Mobilimb J1 the interincisal distance increased from 13 mm to 46 mm. According to literature CPM has so far been used only as adjunctive physical therapy after surgical intervention. On the basis of data in the literature the author is studying the effect of CPM on reduced mobility of the jaws as primary treatment without surgery. PMID- 1449745 TI - [Health and quality. Quality assessment, quality assurance and quality improvement in health care. Concepts and terminology]. PMID- 1449746 TI - [Treatment of primary caries]. PMID- 1449747 TI - [Is the laser useful?]. PMID- 1449748 TI - [Database KLINIK system]. PMID- 1449749 TI - [Complaints about orthodontics]. PMID- 1449750 TI - [Resorbable Vicryl mesh for new attachment after jaw fracture]. AB - The principle of GTR, guided tissue regeneration, was developed by Scandinavian scientists in order to separate epithelium and connective tissue from periodontal ligament cells and bone, thereby eliciting new attachment after marginal periodontitis. In case of jaw fractures loss of attachment may be seen in relation to teeth in the line of fracture, especially after severe dislocation of the fragments. One such patient is reported in whom only emergency treatment was possible during the first 11 days due to a simultaneous cerebral trauma. As anticipated a deep osseous pocket developed on the actual tooth 43 even if the fractures were anatomically repositioned and fixed with osteosynthesis and even if the postoperative course was uneventful. Later, treated by interpositioning of a resorbable Vicryl membrane, new attachment formed with a gain of the order of magnitude of 8 mm with concomitant osseous regeneration. It is concluded that Vicryl mesh would definitely seem to have a place in the treatment of jaw fractures. However, there is an urgent need for a larger collection of meshes than presently available, including both larger sizes and other shapes. PMID- 1449751 TI - [Endodontics for primary teeth. An update]. PMID- 1449752 TI - [Diagnosis of caries in occlusal plane]. PMID- 1449753 TI - [How does the curing lamp operate?]. PMID- 1449754 TI - The feeling of a presence and verbal meaningfulness in context of temporal lobe function: factor analytic verification of the muses? AB - We hypothesized that the feeling of a presence, particularly during periods of profound verbal creativity (reading or writing prose or poetry), is an endemic cognitive phenomenon. Factor analyses of 12 clusters of phenomenological experiences from 348 men and 520 women supported the hypothesis. We conclude that periods of intense meaningfulness (a likely correlate of enhanced burst-firing in the left hippocampal-amygdaloid complex and temporal lobe) allow access to nonverbal representations that are the right hemispheric equivalents of the sense of self; they are perceived as "a presence." The relevance of our results to the theories of Jaynes, Bear, Edelman, and MacLean is discussed. PMID- 1449755 TI - Asymmetries in the spatial localization of transformed targets. AB - This study was designed to examine the contribution of the right cerebral hemisphere in the spatial localization of visual targets for manual aiming. Visual targets were briefly presented to the right and left fields and subjects were required to point either to the target location, or a "mirror" image of the target location with their right or left index finger. Whereas reaction times were faster for left-hand pointing than for right-hand pointing, there was no differential effect of the mirror image transformation. This suggests that left hand reaction time advantages are more related to right hemisphere involvement in the spatial parameterization of the movement than spatial localization of the target. PMID- 1449756 TI - Ideational fluency in Parkinson's disease. AB - Recent research on Parkinson's disease (PD) suggests that executive functions are impaired but that visuospatial functions may be spared. This dissociation has been attributed to dysfunction in ascending dopaminergic pathways affecting the prefrontal cortex. We investigated these ideas in a sample of intellectually intact patients with idiopathic, optimally treated PD (N = 20) and in spouse controls (N = 15); the groups were divided into young (age < 60) and old subgroups, each comparable on education, vocabulary level, and Mini-Mental State scores. Six tasks were selected from a set of factor-referenced cognitive tests to measure three abilities: (1) ideational fluency (ability to generate ideas), (2) flexibility of use (ability to shift mental set), and (3) spatial orientation (ability to perceive spatial patterns). PD patients were impaired only on the ideational fluency factor (p = .01). An age-related deficit was seen on the spatial factor (p < .05) with a trend on the flexibility factor (.05 < p < .10). No interactions were significant. The findings suggest that when age and verbal intelligence are controlled, PD patients show no deficit on purely spatial tasks; in contrast, patients seem less able to generate ideas though capable of shifting from one idea to another. PMID- 1449757 TI - Assessment of the relationship of cerebral hemisphere arousal asymmetry to perceptual asymmetry. AB - This study examined the hypothesis that characteristic individual differences in cerebral hemisphere arousal asymmetry are related to individual differences in perceptual asymmetry observed in verbally based visual half-field tasks. The study used electrophysiological measures of arousal asymmetry rather than behaviorally derived measures (Levy, Heller, Banich, & Burton, 1983). Measures of alpha asymmetry were obtained from 20 right-handed males during a baseline relaxation condition and during a visual half-field version of the lexical decision task. Reaction time measures of perceptual asymmetry were obtained during this task. The results indicated that a basal arousal asymmetry measured at the temporal recording location during the baseline condition was significantly related to individual perceptual asymmetry during the subsequent lexical decision task. This basal arousal asymmetry was relatively stable across different task conditions. A task-related arousal asymmetry measured at the parietal location during the lexical decision task also made a significant contribution in predicting individual perceptual asymmetry. These two measures of individual arousal asymmetry were able to predict 50% of the variance in perceptual asymmetry. The implications of the results for explaining more wide ranging individual differences in behavioral style and personality are discussed. PMID- 1449758 TI - Electroencephalogram asymmetry during emotionally evocative films and its relation to positive and negative affectivity. AB - The purpose of the present study was to determine if there were differences in hemispheric lateralization during the experience of emotions and if those differences were related to personality style. College-age adult subjects selected for high positive and negative affectivity on Tellegen's Multidimensional Personality Questionnaire (MPQ; Tellegen, 1982) viewed video stimuli selected for their emotionally evocative nature and rated the intensity of the emotions they experienced. The ongoing electroencephalogram (EEG) was recorded while they watched the video clips. Analyses of the EEG data revealed that there were differences in regional activation during the emotional video clips, especially for those stimuli selected to elicit either happy or disgust emotions. These results support the hypothesis that the right hemisphere is specialized for the experience of certain negative affects, whereas the left hemisphere is specialized for the experience of certain positive affects. The findings also indicated some support for the theory that individual differences in personality style are related to differing levels of hemispheric arousal. PMID- 1449759 TI - The roles of handedness and stimulus asymmetry in aesthetic preference. AB - When some pictures are mirror reversed, aesthetic evaluations of them change dramatically. Stimulus features that may be important in contributing to this effect are: (a) location of areas of principal interest or weight in the picture space, (b) cues that suggest a direction of motion within the picture. Dextrals and inverted sinistrals preferred paintings with cues suggesting motion proceeding from left to right over their mirror-reversed versions and also preferred those with weight concentrated in the left portions of the picture space. The explanation that best fits these data is that preference is promoted when the picture content encourages attention to its rightmost portions, thus placing a majority of the picture in the left visual field where it is directly processed by the right hemisphere. PMID- 1449760 TI - Visual hemispheric asymmetries depend on which spatial frequencies are task relevant. AB - Observers classified sine-wave and square-wave gratings on the basis of fundamental frequency (Are the bars wide or narrow?) or on the basis of higher harmonic frequencies (Are the bars sharp or fuzzy?). Stimuli were presented in either the left (LVF) or right (RVF) visual field. When the classification was made on the basis of the fundamental frequencies (1 or 3 c/deg), there was a LVF/right hemisphere advantage. However, when the classification was on the basis of a sharp/fuzzy distinction which involved searching for the higher harmonic frequencies, then a RVF/left hemisphere advantage was found. PMID- 1449761 TI - Auditory/verbal and visual/spatial memory in children with complex partial epilepsy of temporal lobe origin. AB - Two groups of epileptic children and a normal control group were administered a Comprehensive Children's Memory Scale (Experimental Edition) which is presently being developed by this author. The first experimental group consisted of 12 children having complex partial seizures of left temporal origin and the second group consisted of 12 children having partial complex seizures of right temporal lobe origin based upon clinical description and EEG/neuroimaging verification. Results indicated: (a) Children with left temporal lobe epilepsy demonstrated significantly lower performance than controls on auditory/verbal memory testing. (b) Children with right temporal lobe epilepsy demonstrated significantly lower performance than controls on visual/spatial memory testing. (c) For the most part, the right and left temporal lobe groups did not significantly differ from each other. However, their performance was in the expected direction; i.e., children with left temporal lobe epilepsy scored lower than right temporal lobe epileptics on auditory/verbal memory testing, and children with right temporal lobe epilepsy scored lower than left temporal lobe epileptics on visual/spatial memory testing. PMID- 1449762 TI - Impaired drawing from memory in a visual agnosic patient. AB - A case is reported of an associative visual agnosic patient who could not draw from memory objects he could recognize, even though he could copy drawings flawlessly. His ability to generate mental visual images was found to be spared, as was his ability to operate upon mental images. These data suggest that the patient could generate mental images but could not draw from memory because he did not have access to stored knowledge about pictorial attributes of objects. A similar functional impairment can be found in some other visual agnosic patients and in patients affected by optic aphasia. The present case allows a discussion of relationships among drawing from memory, imagery, and copying procedures. PMID- 1449763 TI - The organization of arithmetic facts in memory: evidence from a brain-damaged patient. AB - We report a single case study of a brain-damaged patient with impaired arithmetic performance. Three principal findings are presented: First, in a task involving production of answers to simple arithmetic problems, the patient's performance was far better for subtraction than for addition or multiplication. Second, in all arithmetic operations performance was generally much better for problems potentially solvable by rule (e.g., 5 + 0) than for problems requiring retrieval of specific facts (e.g., 5 + 3). Third, the dissociation between subtraction and the other arithmetic operations obtained in the production task was not observed in a verification task. The implications of these findings for claims concerning the organization of stored arithmetic facts are discussed. PMID- 1449764 TI - Fluency versus conscious recollection in the word completion performance of amnesic patients. AB - To examine the relative contribution of fluency and recollection to the word completion performance of amnesics, we administered a task in which patients were told specifically not to utilize previously presented words during stem completion (an Exclusion condition). This condition was contrasted with a standard word completion task in which patients were encouraged simply to complete the stem with the first word that came to mind (an Inclusion condition). Since the exclusion condition necessitated controlled respecification of the initial presentation, it was hypothesized that amnesics would be less able than controls to exclude study list items. Consistent with this hypothesis, the results indicated that the amnesics' performance, unlike that of the alcoholic controls, did not significantly differ as a function of task condition. To examine whether amnesics' conscious recollection could be enhanced, Experiment 2 presented the study list five times. The amnesics now were able to exclude a significant number of items from the study list; however, they still did so considerably less frequently than alcoholic controls. For the alcoholic controls, increasing the number of study trials had little additional effect on their exclusion performance, but it significantly enhanced their inclusion performance. Taken together, these findings suggest that for control subjects, word completion performance is likely mediated by a combination of fluency and recollection, while for amnesic patients, performance is almost exclusively based on the fluency with which an item comes to mind. PMID- 1449765 TI - Gall's psychophysiological concept of function: the rise and decline of "internal essence". AB - Gall did not employ the term "function" to refer to adaptive mental processes or to observable behavior. To the contrary, he and the phrenologists took a traditional concept of function regarding the contribution or duties of a part within the overall "animal economy" and argued that the "faculties" of the soul are among the functions of the nervous system. In particular, he brought this psychophysiological use of the term into his Enlightenment perspective when he aligned it with internal essence, juxtaposed it to its external sign, and argued that the cerebral organs are the material instruments through which the internal faculties manifest themselves in behavior and in the shape of the skull. Gall did not believe that the faculties are a product of the organs but that the organs, being material incarnations of the internal functions, contain the power to express the faculties externally. Purely psychological uses of function are infrequent among the works of Gall and his followers. It was not until the functionalists at the turn of the century that the word was applied to the adaptive utility of mental processes in relation to the environment and not until the advent of behaviorism that it was employed to refer to the end or adaptive utility of a particular behavior. PMID- 1449766 TI - Hemispheric specialization for word classes with visual presentations and lexical decision task. AB - In the present paper we study the possible RH capabilities for the processing of adjectives and verbs of high frequency and medium imagery using a lexical decision task and a horizontal display. In the analysis of both RTs and mean errors, a RVF advantage is obtained. The interaction VF x Word Class did not reach significance. Therefore, we did not find evidence of differences in the visual-field effect for any syntactic class. These results support a LH superiority for the processing of both adjectives and verbs. For the nonword conditions (pseudoverbs and pseudoadjectives), no visual field differences were observed in either group. Methodological aspects are also discussed. PMID- 1449767 TI - Mechanisms and management of filtration bleb failure. PMID- 1449768 TI - Phenotypic similarities between Stargardt's flavimaculatus and pattern dystrophies. AB - Some heredomacular diseases share ophthalmoscopic and morphologic similarities despite being nosologically distinct. In part, this may arise from pathologic reaction patterns such as lipopigment accumulation and drusen deposition which are common to a variety of disorders of the photoreceptor--retinal pigment epithelium--Bruch's membrane complex. Two of these disorders, Stargardt's flavimaculatus and the pattern dystrophies of the retinal pigment epithelium may be especially difficult to differentiate clinically since they are characterised by both a similar ophthalmoscopic appearance and considerable inter and intrafamilial variation in their expression. Stargardt's flavimaculatus may, however, be distinguished from the retinal pigment epithelial pattern dystrophies by certain clinical and morphological features that are outlined below. PMID- 1449769 TI - Leber hereditary optic neuropathy in Australia. AB - Leber hereditary optic neuropathy (LHON) presents with sudden onset of visual loss mainly in young adult males. LHON is not uncommon in Australia, accounting for 2% of invalid blind pensions. We have identified 20 unrelated families carrying mitochondrial DNA mutations associated with LHON and 135 of 291 individuals with documented LHON are currently alive in Australia. The mean age of onset of visual loss for males was 26 years and for females 27 years, with a range from six to 65 years. The mean risk of visual loss was 20% for males and 4% for females. There are over 1750 male and female carriers living in Australia who have not yet lost vision; 600 carriers are under 24 years of age. The expected number of new cases of blindness from LHON is three to four per year. PMID- 1449770 TI - The objective assessment of abnormal eye movements in infants and young children. AB - Recordings of eye movements from infants and young children can be of clinical value in patients with certain neuro-ophthalmological problems. This requires that the characteristics of normal eye movements in this same age-group are known. Using an electro-oculographic technique in a specially developed laboratory we have been able to assess the saccades, binocular and monocular smooth pursuit, binocular and monocular optokinetic nystagmus (OKN), and sustained vestibular rotation in infants and young children; these recordings were performed in one session lasting approximately 35 minutes. The recordings from four children with abnormal eye movements (delayed visual maturation, hemicerebral cyst, congenital ocular motor apraxia, and gaze-paretic nystagmus) are briefly reported and compared to normal eye movements of age-related children. The limitations of this procedure are discussed. PMID- 1449771 TI - The development of fixing and focusing behaviour in normal human infants as observed with the Otago photoscreener. AB - The Otago photoscreener is an optical instrument which gives a very sensitive indication of the accuracy with which a subject's eyes are fixing and focusing. Early experience suggested that this instrument could be used effectively to screen for the presence of amblyogenic factors in pre-verbal infants. This communication describes the development of ocular fixation and focusing in 137 normal infants who were followed at regular intervals during the first year of life. Accurate fixation and focusing was found in 13% of three-month-old infants, in 68% of six-month-old infants and in 76% of one year olds. The levels of 'focusing' visual acuity obtained from the photoscreen data are considerably better than the levels of cortical acuity measured by the standard behavioral and electrophysiological methods. This suggests that human infants fix and focus accurately for a considerable period before they are able to perceive all the details obtained in their retinal images. PMID- 1449772 TI - Familial congenital corneal anaesthesia. AB - Congenital corneal anaesthesia is a cause of severe corneal ulceration and scarring in childhood. Although uncommon, it may be underdiagnosed when present as an isolated entity. Measures such as the use of elbow splints and tarsorrhaphy may be necessary to prevent visual loss. In rare instances, the condition may be inherited. A family is presented with autosomal dominant isolated congenital corneal anaesthesia, and the systemic associations and treatment of the condition are reviewed. PMID- 1449773 TI - A clinical and cytological study of vitamin A deficiency in Kiribati. AB - Vitamin A status was assessed clinically and by conjunctival impression cytology in a selected group under seven years of age in the Republic of Kiribati. A total of 230 children were studied. Of 185 with readable histology, 14.6% were clinically and histologically abnormal; 19.5% were clinically abnormal but histologically normal; and 15.7% were clinically normal and histologically abnormal. The remainder (50.3%) were clinically and histologically normal. There was a significant correlation between clinical disease and histology (P < 0.001). The prevalence of the disease in males was 45.8% and 26.3% in females. The risk of deficiency appeared to increase with advancing age. There was no significant difference between the two villages studied. PMID- 1449774 TI - An abbreviated assessment of ocular exposure to ultraviolet radiation. AB - Individual behaviour has a very large effect on determining the exposure of the eye to solar radiation. To be able to examine the relationship between ocular exposure to ambient ultraviolet radiation and ocular disease, a model was developed previously that assessed cumulative ocular exposure from individual information on work and leisure activities. In this paper, we present a simplified version of the model that uses data on exposure during the middle of the day (9 a.m. to 3 p.m. solar time) during the northern 'summer' months (April to September). The ocular exposure determined by the simplified model is highly correlated with the full model (r = 0.98) and the simplified model predicts 62% of the total ocular exposure. This model should be useful for future epidemiologic studies of sun exposure and eye disease. PMID- 1449775 TI - Development of experimental chronic intraocular hypertension in the rabbit. AB - There are many unanswered questions about chronic glaucoma which cannot be investigated in the available animal models. The present experiments were designed to develop a rabbit model of chronic intraocular hypertension with characteristics similar to human chronic glaucoma by ligating vortex veins or by making single or multiple intraocular injections of 0.5% or 1% alpha chymotrypsin, 20% chondroitin sulphate, 2% hydroxypropyl methylcellulose, 2% sodium carboxymethylcellulose or 1% or 2% methylcellulose. Evaluation was based on the clinical findings, intraocular pressure and the retrograde axoplasmic transport function of the optic nerve using a horseradish peroxidase histochemical technique. Most methods either failed to produce moderate chronic intraocular hypertension or were associated with other complications. However, a reliable and relatively long period (eight weeks) of intraocular hypertension was developed by a series of four intra-anterior chamber injections of 1% or 2% methylcellulose. This model has been proved suitable for the study of structural and functional damage to the retina and optic nerve caused by chronic glaucoma. PMID- 1449776 TI - The effect of cataract extraction with implant in glaucomatous eyes. AB - The effect of cataract surgery in patients with glaucoma controlled by either topical medication or surgery was assessed in 64 patients. At one year there was a small significant fall in intraocular pressure (IOP) for eyes without previous surgery (preoperative IOP 18.9 +/- 4.7, range 12 to 35 mmHg; postoperative IOP 16.3 +/- 3.4, range 10 to 26 mmHg; P < 0.01) and also for those with previous surgery (preoperative IOP 15.0 +/- 4.3, range 3 to 22 mmHg; postoperative IOP 14.2 +/- 3.7, range 6 to 22 mmHg, P < 0.05). There was a significantly greater incidence of high rise in IOP to 30 mmHg or more immediately after operation in patients without (32%) than those with previous surgery (13%) (chi 2 = 3.9; P < 0.05). Complications were minimal in each group. Iridotomy to deliver the nucleus was necessary in nine eyes without and 21 with previous surgery. Cataract extraction usually causes only a small fall in IOP in glaucomatous patients. If a separate corneal section is used there is no loss of function of the filtering bleb in patients with previous glaucoma surgery. PMID- 1449777 TI - The results of combined cataract extraction and trabeculectomy using separate incisions. AB - A method of combined cataract extraction with posterior chamber intraocular lens and trabeculectomy using separate incisions was tested in 44 operations on 38 patients. The mean preoperative intraocular pressure (IOP) of 28.1 +/- 11.7 (range 12 to 56) mmHg on maximum medication was lowered to 13.9 +/- 3.4 (9 to 23) mmHg at one year, with half the eyes still requiring topical medication. The IOP was 40 mmHg or more preoperatively in eight eyes and 20 mmHg or more in only two patients at one year. There were no rises in IOP above 20 mmHg in the early postoperative period (days 1 and 2). Visual acuity was 6/9 or better in 27 and 6/12 in three eyes. There was an expulsive haemorrhage in one case, rupture of the posterior capsule in two eyes and a choroidal detachment in one eye, but no flat anterior chambers. The two-incision method allowed placement of an intraocular lens with good post-operative pressure control. PMID- 1449778 TI - Day-surgery external dacryocystorhinostomy. AB - A retrospective study of patients undergoing day-surgery external dacryocystorhinostomy (DCR) over five years is presented. The patients were medically fit for day-surgery, preferred outpatient to inpatient care, and had appropriate domiciliary support. There was a high success rate with minimal morbidity, similar to findings in an inpatient setting. Patient satisfaction was uniformly high. The author believes that external DCR can be performed on a day surgery basis safely and successfully. PMID- 1449780 TI - Pseudallescheria boydii keratitis. AB - We treated a case of post-traumatic keratitis caused by the soil saprophyte, Pseudallescheria boydii. The injury was caused by a wood splinter which produced a perforating corneal laceration that was primarily repaired. Signs of corneal infection were not evident until the fourth postoperative week. The organism was eradicated by topical miconazole and natamycin. Subsequent penetrating keratoplasty combined with cataract extraction and intraocular lens implantation has achieved a good visual outcome. PMID- 1449779 TI - Histopathologic, immunophenotypic and genotypic analyses in ocular adnexal lymphoproliferative disorders. AB - This study reports on fourteen biopsies from patients presenting to our orbital and oncology service with ocular adnexal lymphoid proliferations between November 1988 to September 1991. The biopsies were studied using histologic, immunophenotypic and genotypic analyses. By histologic criteria, there were two reactive, five indeterminate and seven lymphomatous lesions. On immunophenotypic analysis, there were two monoclonal and 10 polyclonal lesions in the 12 specimens analysed. Genotypic analysis confirmed the histopathologic diagnoses for the reactive lesions by showing them to be germline. It also confirmed that both the histopathologic lymphomas and immunophenotypically monoclonal lesions were clonally rearranged. Genotypic analysis was able to separate the histologically indeterminate group into two subsets: clonally rearranged, of which there was one, and germline, of which there were four. In addition, it demonstrated that immunophenotypic polyclonality cannot always be equated with genotypic polyclonality as was the situation in four out of 10 lesions in our series. The significance of clonal arrangements in the histologically indeterminate and immunophenotypically polyclonal groups can only be determined by prospective study. PMID- 1449781 TI - Atypical mycobacterium keratitis. AB - We present two cases of Mycobacterium chelonae keratitis, both of which followed minor corneal trauma. One case initially showed improvement with medical therapy alone but eventually required penetrating keratoplasty. The second case required surgical intervention to provide tectonic support, but the infection resolved with antibiotic therapy. PMID- 1449782 TI - Limbal nodules in Sweet's syndrome. AB - Sweet's syndrome is acute febrile neutrophilic dermatosis. Conjunctivitis and episceritis have been described with it before. A case of Sweet's syndrome, described here, was found to have limbal nodules with histology similar to the skin lesions. This is the first report of this association. PMID- 1449783 TI - Diazepam and its effects on visual fields. AB - A patient who experienced severe visual field loss whilst taking 100 mg of diazepam that reverted to normal on cessation of the drug is described. Diazepam affects GABA inhibitory neurones and the physiology of this in the retina and visual cortex is reviewed. PMID- 1449784 TI - Excimer laser keratectomy. PMID- 1449785 TI - Post-cataract cryptococcal endophthalmitis. PMID- 1449786 TI - B and T cell leakiness in the scid mouse mutant. AB - Recombination of antigen receptor gene elements (V, D and J) that code for Ig and TCR variable regions is defective in the scid mouse mutant. However, the defect is not absolute. Developing scid lymphocytes occasionally succeed in forming a productive VDJ and VJ rearrangement at two critical loci (e.g., IgH/IgL or TCR beta/TCR alpha), and given the appropriate stimuli, differentiate into clones of functional B or T cells. Scid mice with detectable B and/or T lymphocytes are referred to as leaky. This review considers the nature and possible basis of B and T cell leakiness in scid mice. PMID- 1449787 TI - Domestic animal models of severe combined immunodeficiency: canine X-linked severe combined immunodeficiency and severe combined immunodeficiency in horses. AB - This review describes the clinical, immunologic and pathologic features of two naturally-occurring models of severe combined immunodeficiency (SCID) in domestic animals that represent different forms of human SCID. Canine X-linked SCID (XSCID) has an X-linked recessive mode of inheritance and, as such, represents a model for the most common form of human SCID in the United States. Affected dogs have normal percentages of circulating B cells and low to normal percentages of phenotypically mature, but nonfunctional T cells. Severe combined immunodeficiency in the horse is an autosomal recessive form of SCID that is characterized by a profound lymphopenia affecting both the B and T cell lineage most likely due to a lymphoid stem cell defect. Since these diseases are naturally-occurring in an outbred species, like man, they represent unique animal models of their respective human counterparts in which to determine the underlying immunologic defect(s), to evaluate novel approaches to immunotherapy or gene therapy, and to evaluate therapeutic regimens for opportunistic infections associated with SCID. PMID- 1449788 TI - Perinatal HIV transmission facts and controversies. AB - In 1992, HIV infection in children is essentially due to vertical or perinatal transmission, i.e. from the mother to the fetus and neonates. This is a particularly serious public-health problem in Africa where the percentage of infected women of child bearing age is as high as 20% in some suburban areas. During the last few years, three important points have been established. (i) In Europe and North America, the rate of perinatal transmission is between 15 and 25% and appears to have remained relatively stable with time in various prospective cohorts. (ii) Considerable efforts have been directed at defining the optimal methods for early diagnosis of HIV infection in the infants. At present viral cultures and gene amplification of HIV DNA by polymerase chain reaction are the most promising procedures for early diagnosis within the first 6 months of life. (iii) Finally, the course of the disease in the infected infant has been well characterised, it takes two main forms--that of an early and severe disease or that of a slowly progressive infection: In addition, follow-up is now sufficient to confirm that children with negative tests at 15 months are indeed uninfected. However, knowledge is lacking in a number of essential areas. These include the exact timing of transmission (in utero, during delivery or post partum), the relative frequency of transmission during each period, the mechanism(s) involved (particularly the role of the placenta), and, finally, the influence of maternal, fetal and viral factors. Answers must be found rapidly in order to develop preventive therapy, to identify women who may have an increased risk of transmitting the virus, to develop a reliable antenatal diagnostic test and, finally, to be in a better position to inform HIV-seropositive women of the relative risks. PMID- 1449789 TI - Gene therapy for primary immunodeficiency disease. AB - Gene therapy offers the potential for developing innovative new treatments for both inherited monogenic diseases as well as polygenic and acquired disorders. For most potential clinical applications, the technology has not yet progressed to the stage where it might be reasonably tested. Problems to be solved include the isolation and characterization of the genes involved, the development of gene delivery systems that will permit efficient gene insertion in the affected cells and tissues, and the development of mechanisms to control or appropriately regulate expression of the introduced genes. The primary immunodeficiency diseases as a group actually lend themselves to the development of gene therapy strategies with current technology more readily than almost any other class of disease. Theoretically any genetic disease that can be successfully treated by allogeneic bone marrow transplantation is a potential candidate for gene therapy directed at correcting the patient's own totipotent bone marrow stem cells. In addition, some disorders lend themselves to genetic correction of more mature cells, although gene transfer in this treatment strategy might have to be repeated periodically. The rationale and preliminary results of the first gene therapy protocol for ADA deficiency SCID are described and strategies for developing somatic cell gene therapy for the other primary immunodeficiency diseases are discussed. PMID- 1449790 TI - Genome exclusion and gametic DAPI-DNA content in the hybridogenetic Bacillus rossius-grandii benazzii complex (Insecta Phasmatodea). AB - Among Sicilian stick insects, two hybridogenetic complexes have been discovered: Bacillus rossius-grandii benazzii and B. rossius-grandii grandii, which also produce androgenetic offspring. The egg maturation of the former is analyzed here through DAPI fluorometry, which, besides the assessment of the meiotic stages, also allows their DNA measurements and the analysis of sperm-head evolution into male pronuclei in these polyspermic eggs. Hybridogenetic eggs undergo an extrasynthesis of chromosomes, because two groups of n autobivalents (4C each) are segregated at metaphase 1st; the two groups must correspond to the pure parental species haplosets. Then the grandii chromosomes degenerate (1st polar body), while the rossius chromosomes divide further to produce two groups of n autodiads (2C each); one of them degenerates (2nd polar body), and the other is ready to perform syngamy (female pronucleus). Meanwhile, several B. grandii sperm evolve into male pronuclei by doubling their DNA (from 1C to 2C content) and assuming an interphase nucleus appearance. If regular mixis occurs, the F1 hybrid constitution is restored but, if it fails, a fusion between two sperms may occur, originating fully paternal descendants (natural androgenesis). The genome exclusion mechanism of stick-insect hybridogens appears to be more primitive than those observed in the already known hybridogenetic complexes of Poeciliopsis and Rana esculenta. Unfertilized eggs of hybridogens are capable of self-activation, but the cytology of the related clonally reproducing B. whitei indicates that its parthenogenetic mechanism stems from the hybridization event (hybrid theory) rather than from tychoparthenogenetic potentialities (spontaneous theory). PMID- 1449792 TI - Demonstration of a stage-specific expression of the ZFY protein in fetal mouse testis using anti-peptide antibodies. AB - The zinc finger Y (Zfy) gene is located on the Y chromosome of all placental mammals. Although it is phylogenetically conserved and is expressed in mouse fetal testis, it is not the sex determining Y (Tdy) gene. To address the possible function of the Zfy gene in mice, the distribution of Zfy protein in fetal mice was investigated by immunocytochemical staining using several specific antisera against synthetic peptides of the mouse Zfy protein. Analysis of various fetal tissues at different embryonic stages demonstrated a specific staining only in fetal testis. In particular, reactive protein was initially observed in male fetal gonads at day 11.5 postcoitum (p.c.). The immuno-staining intensified in fetal testes at day 12 and 12.5 p.c., decreased drastically in those at day 13 and 14 p.c. and became undetectable in those at day 15 p.c. and beyond. The reactive molecules were distributed mostly within the seminiferous tubules of the embryonic testis. The present observations confirm the previous findings with RT PCR analysis and indicate that Zfy or Zfy-like protein is expressed in stage specific manner during early testis differentiation. Its location in the seminiferous tubules suggests a possible role in early germ cell development. PMID- 1449793 TI - Mediation of the actions of insulin and insulin-like growth factor-1 on preimplantation mouse embryos in vitro. AB - Previous studies showed that both insulin and insulin-like growth factor-1 (IGF 1) stimulate metabolism and growth of preimplantation embryos. Because the effects of insulin occur with very low doses, it was suggested that its effects were mediated by its own receptors. However, the effects of IGF-1 occurred at higher doses, suggestive of cross reaction with the insulin receptor but still in the range for mediation via its own receptor. The aim of this study was to investigate the mediation of the metabolic and growth effects of insulin and IGF 1 using a specific insulin receptor antagonist. The antagonistic B-10 Fab fragment (B-10f) completely blocked stimulation of protein synthesis by both insulin and IGF-1, indicating that the insulin receptor mediates this action of both hormones. Alternately, only insulin's stimulation of inner cell mass mitogenesis and morphological development was inhibited by the B-10 Fab fragment. This showed that growth stimulation by insulin and IGF-1 was mediated via different receptors, insulin through its own receptor and IGF-1 through some other receptor. However, mediation via the IGF-2 receptor is not excluded since IGF-1 stimulates compaction when there is evidence for only the presence of the IGF-2 receptor. In summary, insulin or IGF-1 at physiological concentrations stimulates preimplantation mouse embryos, suggesting an important role for both these growth factors in early development. PMID- 1449791 TI - Analysis of the expression of a large number of novel genes isolated from mouse prepubertal testis. AB - The analysis of genes expressed in a restricted temporal and spatial manner during spermatogenesis has given insights into different gene-regulatory mechanisms active in germ cells. However, very few genes have so far been described that are predominantly active in spermatogonia and the early meiotic cell types of testis. To isolate a battery of such genes, more than 100 different mRNA molecules were isolated from a mouse prepubertal testicular cDNA library, and their expression patterns in different tissues analyzed. Thirty mRNAs, 26 of them previously not described in the literature, were found to be predominantly expressed in mouse testis. A detailed analysis of their expression patterns identified a number of mRNA molecules differentially expressed in testicular cell types, including both germ cells and somatic cell types. Characterization of these mRNAs also revealed five distinct temporal phases of gene expression during prepubertal germ cell development. Three different genes, mainly active in the spermatogonial and the early meiotic cell types of testis, were isolated and will be used to characterize further stage-specific gene expression during germ cell differentiation. PMID- 1449794 TI - Increasing carbon dioxide from five percent to ten percent improves rabbit blastocyst development from cultured zygotes. AB - One-cell rabbit zygotes were cultured at 39 degrees C in basal synthetic medium II (BSM-II) with 5%, 10%, or 15% CO2 and humidified air to determine the effect of CO2 concentration on development in vitro. After 4 days in culture, 37% of the embryos grown in 10% or 15% CO2 had reached the hatching blastocyst stage, but only 10% of the embryos were hatching when cultured under 5% CO2 (P = 0.01). Over all blastocysts, cell numbers were 207, 246, and 205 for the 5%, 10%, and 15% CO2 treatments, respectively. In a second experiment to determine if there was a beneficial effect, particularly at the blastocyst stage, of a higher concentration of CO2, embryos were cultured 4 days in either 5% or 10% CO2 or for 2 days in 5% CO2 followed by 2 days in 10% CO2. The numbers of blastomeres per embryo and embryo diameter were greater (P < 0.05) in embryos cultured continuously in 10% CO2 or in 10% CO2 only during days 3 and 4 of culture than in embryos cultured continuously in 5% CO2. In a third experiment, one-cell rabbit zygotes were cultured with 5% or 10% CO2 in a defined, protein-free medium consisting of 1:1 RPMI 1640 and Dulbecco's modified Eagle's medium. The proportion of embryos hatching and cell counts were significantly greater (P < 0.01) when cultured in the presence of 10% CO2. These data indicate that a 10% CO2 atmosphere exerts a beneficial effect on the development of zygotes into expanding and hatching rabbit blastocysts in vitro. PMID- 1449795 TI - In vitro fertilization, development, and implantation after exposure of mature mouse oocytes to visible light. AB - Mature mouse oocytes were exposed prior to in vitro fertilization to visible light during 1, 2, or 4 hr at an intensity of 4,000 lux. Compared to controls cultured under identical conditions but protected from light, exposed eggs did not show any significant modification of cleavage speed and rate. After transfer of blastocysts obtained in vitro in uteri of pseudopregnant females, the implantation rate and the proportion of normal fetuses were not found to be different in relation to preliminary light exposure of oocytes fertilized and cultured in vitro. PMID- 1449796 TI - Biosynthesis of prostaglandins by human spermatozoa in vitro and their role in acrosome reaction and fertilization. AB - Five homogenates of human sperm cells were separately incubated with [14C]arachidonic acid in the presence of reduced glutathione, L-tryptophan, and haematin as cofactors. The cyclooxygenase products of arachidonic acid metabolism were extracted, separated, and measured for their radioactivity. The rate of formation of prostaglandin (PG)D2, PGE2, PGF2 alpha, 6-keto PGF1 alpha, and thromboxane (TX)B2 were 18.0 +/- 1.11, 10.9 +/- 0.68, 5.8 +/- 0.21, 3.9 +/- 0.13 and 6.6 +/- 0.52 pmol/10(6) cells/min, respectively. These results are discussed in relation to the hypothesis that cyclooxygenase metabolites of certain polyunsaturated fatty acids play an important part in the sperm acrosome reaction and fertilization. PMID- 1449797 TI - Characterization of male meiotic germ cell-specific antigen (Meg 1) by monoclonal antibody TRA 369 in mice. AB - We have identified a male meiotic germ cell-specific antigen (Meg 1) with monoclonal antibody (mAb) TRA 369 in mice. The Meg 1 antigen was strongly expressed in specific steps of meiotic germ cells from pachytene spermatocyte to early spermatid, and not in other germ cells or somatic cells. Immunohistochemical examination revealed that the antigen was localized to the cytoplasm and was not distributed in the nucleus or on the cell surface. This antigen was demonstrated to have a molecular weight of 93 kDa and an isoelectric point of 5.2 by Western blotting. This molecule was first detected in the testis of 13-day-old mouse when pachytene spermatocytes first appeared. Thus this is a differentiation-specific antigen in male meiotic germ cells, and mAb TRA 369 is a useful tool to study the regulation of germ cell differentiation and to define germ cell development in a molecular level. PMID- 1449798 TI - Adsorption of oviductal fluid proteins by the bovine sperm membrane during in vitro capacitation. AB - 125I-labeled oviductal fluid (ODF) proteins and antiserum to ODF were used to determine whether ODF proteins associate with the sperm membrane during in vitro capacitation. Luteal and nonluteal pools of ODF were obtained from oviduct catheters during the estrous cycle. Washed sperm (50 x 10(6) sperm/ml) were incubated up to 4 h in a protein-free modified Tyrode's medium (MTM), or MTM supplemented with 40% ODF, or 0.5 ng 125I-labeled ODF proteins. Solubilized sperm membrane proteins and incubation media containing ODF proteins were separated by gel electrophoresis. Membranes isolated from bovine sperm, previously incubated with ODF, adsorbed five 125I-proteins: A doublet at 85-95 kDa, and others at 24, 34, 53, and 66 kDa. The amount of 66 kDA 125I-protein associated with the sperm decreased during the incubation, whereas the amount of 85 to 95-kDa protein did not. Western blot analyses also detected the presence of ODF proteins (53, 66, 85 95, and 116 kDa) in solubilized membranes from sperm incubated in ODF. The 85 to 95-kDa protein in ODF decreased in apparent molecular weight by 5 kDa when associated with the sperm membrane. At 53 kDa, ODF proteins which associated with sperm were transformed from two to three separate proteins. These studies indicate that the surface of sperm is modified by adsorption of ODF proteins to the membrane during in vitro capacitation. PMID- 1449799 TI - Protein synthesis requirements during resumption of meiosis in the hamster oocyte: early nuclear and microtubule configurations. AB - The organization of chromatin and cytoplasmic microtubules changes abruptly at M phase entry in both mitotic and meiotic cell cycles. To determine whether the early nuclear and cytoplasmic events associated with meiotic resumption are dependent on protein synthesis, cumulus-enclosed hamster oocytes were cultured in the presence of 100 micrograms/ml puromycin or cycloheximide for 5 hr. Both control (untreated) and treated oocytes were analyzed by fluorescence microscopy after staining with Hoechst 33258 and tubulin antibodies. Freshly isolated oocytes exhibit prominent nucleoli and diffuse chromatin within the germinal vesicle as well as an interphase network of cytoplasmic microtubules. After 4-4.5 hr in culture, most oocytes were in prometaphase I of meiosis as characterized by a prominent spindle with fully condensed chromosomes and numerous cytoplasmic asters. After 5-5.5 hr in culture, microtubule asters are no longer detected in most cells, and the spindle is the only tubulin-positive structure. Incubation for 5 hr in the presence of inhibitors does not impair germinal vesicle breakdown, chromatin condensation, kinetochore microtubule assembly, or cytoplasmic aster formation in the majority of oocytes examined; however, under these conditions, a population of oocytes retains a germinal vesicle, exhibiting variable degrees of chromatin condensation and cytoplasmic aster formation. Meiotic spindle formation is inhibited in all oocytes. These effects are fully reversible upon culture of treated oocytes in drug-free medium for 5 hr. The data indicate that meiotic spindle assembly is dependent on ongoing protein synthesis in the cumulus-enclosed hamster oocyte; in contrast, chromatin condensation and aster formation are not as sensitive to protein synthesis inhibitors during meiotic resumption. PMID- 1449800 TI - Determination of enzyme activities of energy metabolism in the maturing rat oocyte. AB - Enzyme activities were determined quantitatively in individual rat oocytes to study their energy metabolism during maturation. Low hexokinase activity and high activities of lactate dehydrogenase and enzymes in the phosphate pathway, i.e., glucose 6-P and 6-P gluconate dehydrogenases, were characteristic of immature oocytes. Hexokinase may be a rate-limiting enzyme that enables oocytes to use glucose as an energy source. During maturation, the activities of hexokinase, phosphofructokinase, and malate dehydrogenase increased significantly, suggesting that the glycolytic pathway, as well as the tricarboxylic acid cycle, developed as the first meiotic division proceeded. In contrast, the activities of glucose 6 P and 6-P gluconate dehydrogenases decreased in maturing oocytes. The observation that the enzyme pattern in mature oocytes resembles more closely that in somatic cells appears to be significant, especially in light of previous studies showing this developmental trend in preimplantation embryos. PMID- 1449801 TI - In vitro decondensation of mammalian sperm and subsequent formation of pronuclei like structures for micromanipulation. AB - In this study, we describe an efficient protocol for the formation of in vitro developed pronuclei for micromanipulation techniques. Our approach involved incubation of demembranated or permeabilized mammalian sperm in a phosphate buffer supplemented with heparin and beta-mercaptoethanol. Under the prevailing conditions, we achieved a uniform and reliable synchronous decondensation of sperm nuclear DNA. This initial decondensation facilitated the removal of mammalian protamines upon subsequent incubation in an amphibian egg extract. The interchange of protamines for histones to stabilize the DNA structure is recognized as a prerequisite for pronuclear formation. Furthermore, immunocytochemical studies have revealed that pronuclear development is accompanied by the formation of a nuclear lamina with corresponding DNA synthesis. The method described gave a high yield of nuclei during pronuclear formation. Ultimately, our aim is to transfer the in vitro-developed pronuclei into mammalian oocytes by micromanipulation. This novel procedure may prove useful in alleviating severe male factor problems especially in oligozoospermic cases in our in vitro fertilization center. PMID- 1449802 TI - Parthenogenetic development of bovine oocytes treated with ethanol and cytochalasin B after in vitro maturation. AB - The present study was conducted to investigate the effects of different culture durations (24-36 hr) on bovine oocyte maturation in vitro and the effect of the presence or absence of cumulus cells at the time of treatment to induce parthenogenetic activation (exposure to ethanol and cytochalasin B; CB) (experiment I). The effects of dosage (2.5 or 5.0 micrograms/ml) and incubation time (2.5, 5, or 10 hr) in CB (experiment II) on the subsequent development to the blastocyst stage in vitro was also investigated. In experiment I, cleavage and development to the blastocyst stage were not affected by the presence or absence of cumulus cells at the time of parthenogenetic activation. However, the 24-hr culture duration for in vitro maturation had a significantly lower rate of development to the blastocyst stage than the longer culture durations (27-36 hr). In experiment II, treatment with 5 micrograms/ml CB for 5 hr showed the highest percentage of development to blastocyst in the oocytes matured for both 27 and 30 hr. To determine the viability of the parthenogenetic embryos (morulae and blastocysts), four recipient heifers received two embryos each, and one heifer was found to be pregnant on day 35 following transfer. Although fetal heartbeat was not observed, the subsequent estrus was prolonged in all heifers. The present results demonstrate development of in vitro-matured, parthenogenetically activated bovine embryos up to the preimplantation stage. PMID- 1449803 TI - Mucin genes and the proteins they encode: structure, diversity, and regulation. AB - Mucins are the structural components of the mucus gels that protect the respiratory, gastrointestinal, and reproductive tracts. These polydisperse glycoproteins (250,000 to 20,000,000 D) are approximately 80% carbohydrate on a mass basis and have a high intrinsic viscosity due to their large size and extreme hydrophilicity. Mucin oligosaccharides, the structures responsible for this hydrophilicity, are heterogeneous in size and structure but are chiefly O linked, i.e., they initiate from N-acetylgalactosamine residues attached to threonine and serine residues of the polypeptide backbone. Our understanding of the structure of mucins has advanced rapidly in the last few years with the isolation and sequencing of cDNA clones that encode mucin polypeptide backbones. All currently well-characterized mucins have been found to contain extended arrays of tandemly repeated peptides rich in potential O-glycosylation sites. Less is known about the unique sequences that flank the tandem repeat arrays of secretory mucins, but currently available information indicates that these flanking regions contain cysteine-rich stretches that participate in mucin oligomer formation. Thus, secretory mucins appear to consist of oligomers containing heavily glycosylated domains flanked by unique sequences required for polymerization. Progress has also been made in characterizing the genes that encode mucins. At least four human mucin genes are known at present, although many others may remain to be discovered. Moreover, much work remains before we gain an understanding of the mechanisms involved in the expression of mucin genes and their tissue-specific regulation. PMID- 1449804 TI - Ragweed sensitization-induced increase of myosin light chain kinase content in canine airway smooth muscle. AB - Previous studies have identified changes of mechanical properties of airway smooth muscle (ASM) from a canine model of atopic airway hyperreactivity. These changes, including increased maximum shortening capacity (delta Lmax) and early shortening velocity (Vo), may be responsible for the airway hyperresponsiveness in asthma. We have suggested that these changes may be due to increased actomyosin ATPase activity, controlled via phosphorylation of the 20 kD myosin light chain (MLC20) by MLC kinase (MLCK). Therefore, ATPase activity, MLC20 phosphorylation, and MLCK content and activity were assessed in tracheal and bronchial smooth muscles (TSM and BSM) of ragweed pollen-sensitized dogs (S) and their littermate controls (C). Specific ATPase activities from STSM and SBSM were significantly higher than their control counterparts (CTSM, CBSM). Phosphorylation of MLC20 in STSM was greater both at rest and during electrical stimulation due to the increased amount of MLCK in STSM and SBSM by 30 and 25%, respectively. MLCK activity was also increased significantly in STSM and SBSM (from 46.99 +/- 8.33 and 42.85 +/- 5.92 to 91.9 +/- 6.43 and 64.12 +/- 7.88 32P mmol/mg fresh tissue weight/min respectively [mean +/- SEM]). When normalized to the amount of MLCK in the tissue, however, specific MLCK activity in STSM and SBSM was similar to that in controls. It is unlikely that myosin phosphatase plays any role in the changes of MLC20 phosphorylation in sensitized animals. Peptide mapping showed no visible change in primary structure of MLCK in STSM and SBSM compared with those of controls. We report that ASM actomyosin ATPase activity is increased in STSM and SBSM. The increased ATPase activity is the result of increased MLC20 phosphorylation, the latter likely resulting from the increased MLCK content, which may account for the hyperresponsiveness found in ASM from these animals. PMID- 1449805 TI - Quantifying proliferation of cultured human and rabbit airway smooth muscle cells in response to serum and platelet-derived growth factor. AB - Development of suitable methods for the quantification of the proliferative response of airway smooth muscle (ASM) cells in culture will assist the investigation of the cellular mechanisms underlying the hyperplasia and hypertrophy of ASM as seen in asthmatic airways. In this study, two rapid and simple colorimetric assays have been modified to enable the growth of human bronchial and rabbit tracheal smooth muscle in culture to be assessed. One method depends upon the reduction by living cells of the tetrazolium salt MTT to form a blue formazan product, whereas the other relies on rapid binding of the dye Coomassie brilliant blue to protein at acidic pH. Experiments demonstrated the validity of both assays in quantifying the proliferative response of cultured human and rabbit ASM cells. The increase in optical density observed for each assay correlated directly, throughout the duration of culture, with the increase in cell number determined by hemocytometry in human and rabbit ASM cells proliferating in response to fetal calf serum (1.25 to 10%). This relationship held also for rabbit tracheal ASM cells proliferating in response to the heterodimer of platelet-derived growth factor (1 to 50 ng/ml). Application of these methods to adherent proliferating cultures of human and rabbit ASM cells demonstrated their adaptability to the generation of growth curves in response to serum and to a defined growth factor. These methods allow both total cellular protein and proliferation to be estimated in human and rabbit ASM cells in culture, using assays that are rapid, reproducible, inexpensive, and easy to perform while negating the use of radioisotopes. It is intended that these additional methods should be useful in delineating some of the mechanisms that might contribute to the proliferative response of these cells--particularly since there has been a resurgence in interest in culturing smooth muscle cells derived from the airways. PMID- 1449806 TI - Early maturation of force production in pig tracheal smooth muscle during fetal development. AB - The contractility of airway smooth muscle is fully established at late term at birth but its responsiveness during fetal life has not been defined. In this study, the contractile force of airway smooth muscle to acetylcholine (ACh), K+ depolarizing solution, and electrical field stimulation (EFS) was measured in tracheas from small fetal pigs. Contraction to either agonist and to EFS was detectable in fetuses of as low as 9 g body weight, which corresponds to approximately 36 days of gestation. Isometric force increased progressively with age, reaching 4.1 +/- 0.4 mN for K+ and 5.8 +/- 0.5 mN for ACh (10(-4) M) at 600 g fetal weight (90 days). However, when normalized for cross sectional area of smooth muscle, the stress was essentially the same from 17- to 600-g fetuses. (K+: 17 g = 74.4 +/- 10.6 mN/mm2, 600 g = 89.3 +/- 13.0 mN/mm2; ACh [10(-4) M]: 17 g = 76.3 +/- 16.0 mN/mm2, 600 g = 127.0 +/- 13.0 mN/mm2). The sensitivities of the various groups to ACh were not significantly different (e.g., EC50: 30 g = 4.0 +/- 0.2 x 10(-6) M, 600 g = 3.7 +/- 1.1 x 10(-6) M). EFS produced frequency dependent contractile responses in all groups. With increasing fetal size, there was a corresponding increase in force. When this force was normalized to a maximum ACh response (10(-4) M), there was no significant difference between groups of fetuses. Histologic examination showed the major tissue components of the trachea were present in fetuses above 7 g. Immunocytochemistry detected myosin, caldesmon, and filamin in the smooth muscle from fetuses of 7 g and above, showing that contractile and actin-binding proteins were present from a very early age. It is concluded that smooth muscle contractile function is well developed very early in fetal life in pigs. PMID- 1449807 TI - Secretory proteins and glycoconjugates synthesized by human tracheal gland cells in culture. AB - To study the proteins and glycoconjugates synthesized by serous cells from human tracheal glands (HTG), isolated HTG cells were cultured in the presence of radiolabeled precursors 14C-proline, Na2(35)SO4, and 3H-fucose. The secretory 14C/35S/3H-radiolabeled proteins and glycoproteins, de novo synthesized by HTG cells, were analyzed by gel filtration chromatography. We observed the incorporation of 14C-proline into antileukoprotease and an unknown 30 kD protein, and the incorporation of 35SO4-- and 3H-fucose into high molecular weight glycoconjugates and sulfoconjugates (M(r) > 1,000,000) and into components with apparent M(r) of approximately 250 and 100 kD. After specific chemical and enzymatic treatment, the 35S- and 3H-glycoconjugates were shown to be -O-linked mucin-like glycoproteins and proteoglycans. These results show that cultured HTG cells synthesize some of the macromolecules identified in bronchial secretions. PMID- 1449808 TI - The role of the nonciliated bronchiolar epithelial (Clara) cell as the progenitor cell during bronchiolar epithelial differentiation in the perinatal rabbit lung. AB - Although it is well established that the nonciliated bronchiolar epithelial (Clara) cell serves as the progenitor for itself and ciliated cells in the adult lung following bronchiolar epithelial injury, the nature of this relationship during development has not been well characterized. To define the pattern of proliferation and differentiation of bronchiolar ciliated and nonciliated cells, lungs of fetuses and offspring from time-mated New Zealand White rabbits, ranging in age from 24 days of gestation to 25 wk postnatal (PN), were fixed by airway infusion and embedded for simultaneous light and transmission electron microscopy. Three categories of cells could be distinguished in terminal bronchioles: nonciliated cells with abundant glycogen and variable numbers of organelles; nonciliated cells with little glycogen, large numbers of polyribosomes, and variable numbers of basal bodies; and ciliated cells with cilia of varying height. Together, both types of nonciliated cells were 100% of the epithelium at 24 and 27 days gestation age (DGA). At 30 days DGA, they were 85% of the population; at all postnatal ages, they ranged from 75 to 81% of the total population. Nonciliated cells with polyribosomes and basal bodies were 10 to 20% of the total nonciliated cell population between 24 DGA and 1 wk PN and not found thereafter. Ciliated cells were not observed in animals younger than 30 DGA. Labeling indices of bronchiolar epithelium in fetuses of pregnant rabbits injected with tritiated thymidine, as determined by autoradiography, were 57 cells per thousand at 28 DGA (1 h postinjection [PI]), 76 at 29 DGA (24 h PI), and 114 at 30 DGA (48 h PI).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449809 TI - Modulation of eosinophil chemotaxis by interleukin-5. AB - Eosinophilia and eosinophil function are regulated by cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5). We have investigated the modulatory role of IL-5 on N formyl-methionyl-leucyl-phenylalanine (FMLP), neutrophil-activating factor (NAF/IL-8), platelet factor 4 (PF4), and cytokine-induced chemotaxis of eosinophils from normal individuals. These eosinophils show a small chemotactic response toward PF4 but not to NAF/IL-8 and FMLP. Preincubation of eosinophils with low concentrations of IL-5 caused significantly increased responses toward PF4 and induced a significant chemotactic response toward FMLP and NAF/IL-8. In marked contrast, IL-5 (or IL-3) priming of eosinophils from normal donors resulted in a strong inhibition of GM-CSF-induced chemotaxis. A similar decrease in the chemotactic response toward GM-CSF was observed in eosinophils derived from allergic asthmatic individuals. This finding suggests that the latter eosinophils may have had a prior exposure to IL-5 (or IL-3). Washing of the cells after priming did not abrogate the inhibition of the GM-CSF response. Our data indicate that at low concentrations IL-5 is an important modulator of eosinophil chemotaxis, causing selective upregulation or downregulation of chemotactic responses toward different agents. PMID- 1449810 TI - Late results (50 to 182 months) of the Jatene operation. AB - Between May 1975 and August 1991, 184 patients with transposition of the great arteries (TGA) were operated upon by Jatene operation. One hundred and sixteen underwent corrective surgery prior to June 1987 with a follow-up period of between 50 and 182 months. The ages of these 116 patients ranged from 1 day to 84 months (11.53 +/- 15.98). Eleven percent were less than 1 month old, 38% were between 1 and 6 months, 29% between 7 and 12 months and 22% were older than this. Eighty-eight patients (76%) were boys and the weight ranged from 2.4 to 17.0 kg (6.39 +/- 3.38). Thirty-eight patients (20.7%) died in the immediate postoperative period. Of the survivors, 5 died in the late follow-up between 9 and 66 months (endocarditis at 9 and 66 months; gastroenteritis at 20 months; sudden death at 48 months; and during reoperation for relief of pulmonary stenosis (PS) at 60 months). Of the surviving 73 patients, 24 (32.9%) are anatomically normal at a mean period of 92.5 months postoperatively. Twenty-two (30.1%) have dysfunctions without clinical repercussion. Nineteen (26%) have had no recent evaluation and 8 (11%) were submitted to reoperation or angioplasty for relief of PS. Ninety-eight percent of the patients have normal left ventricular function. The majority of the patients surviving 50 to 182 months are in good clinical condition and if dysfunctions are present these show no progression or severe hemodynamic alterations. PMID- 1449811 TI - Induced hypothermia in the management of refractory low cardiac output states following cardiac surgery in infants and children. AB - Post-operative low cardiac output states remain a major cause of mortality following cardiac surgery in infants and children. Since 1979 we have used moderate induced whole-body hypothermia in the management of low-output states refractory to conventional modes of therapy. This is based not only upon the relationship between body temperature and oxygen consumption, but also on experimental work showing a beneficial effect of cooling upon myocardial contractility, particularly when there is pre-existing impairment of ventricular function. Between July 1986 and June 1990, 20 children with refractory low-output states were cooled by means of a thermostatically controlled water blanket to a rectal temperature of 32-33 degrees C. The median age was 12 months (1 week-11 years) with a median weight of 6 kg (3.5-33 kg). Ten children survived to leave hospital while a further two made a haemodynamic recovery. There was a marked reduction in heart rate (P < 0.001). The mean arterial pressure rose (P = 0.037) while there was a fall in mean atrial pressure (P < 0.001). There was a significant improvement in the urine output (P = 0.002). A fall in the platelet count (P < 0.001) was not accompanied by any change in the white cell count (P = 0.15). Although it is impossible to say whether cooling influenced the outcome in any of these children, it was usually effective in stabilising their clinical condition. The technique is simple and has a sound theoretical basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449812 TI - Twelve year experience with the modified Blalock-Taussig shunt in neonates. AB - Between 1978 and 1990, 53 consecutive modified Blalock-Taussig (MBT) shunts were performed on 51 neonates with cyanotic congenital heart disease using 3 mm-5 mm Gore-Tex grafts. Only 4 of these children had uncomplicated tetralogy of Fallot. The remainder had more complicated pathology requiring urgent intervention. Retrospective analysis of the acute and long term results was performed with 100% follow-up, ranging from 1 month to 12 years (mean 3 years). There were 3 (6%) early deaths (within 30 days of operation) and 17 (33%) late deaths. Of the late deaths, 2 died after further palliation, 2 died after total correction and 13 died suddenly at home. Post mortem examination of the 13 sudden deaths revealed blocked shunts in only 3. Actuarial survival at 2 years was 58%. Shunt patency at 12 months was 87% and at 2 years, 62%. No patient used their initial MBT shunt for more than 40 months. Although this shunt provides good initial palliation, there is a high incidence of late sudden death. We are also concerned about the limited life span of the shunt which partly (3/13) explains the sudden deaths. Therefore we have adopted an aggressive approach to re-study by angiography within 3 months of surgery. PMID- 1449813 TI - The effects of preoperative aspirin therapy on platelet function in cardiac surgery. AB - Extracorporeal circulation is known to have profound effects upon platelets. Changes in platelet function were assessed in 20 patients undergoing elective coronary artery bypass grafting (CABG) who stopped taking aspirin (100 mg per day) 5-7 days before the operation compared with 20 patients undergoing aortic valve replacement (AVR) who had never taken anticoagulants or aspirin. Platelet aggregometry was carried out using the turbidimetric technique (inducing agents: adenosine diphosphate (ADP) 1.0 and 2.0 mumol/l; collagen 4 micrograms/ml; epinephrine 25 mumol/l), and maximum aggregation as well as the maximum gradient of aggregation were monitored before, during, and after cardiopulmonary bypass (CPB) until the 1st postoperative (p.o.) day. Until the 1st p.o. day blood loss was significantly higher in the CABG (890 +/- 160 ml) than in the AVR patients (420 +/- 120 ml). A total of 8 units of packed red cells (PRC) were given in the CABG group, whereas no homologous blood was necessary in the AVR patients (P < 0.05). The aggregation variables of the CABG patients were lower than in the AVR patients as early as after the induction of anesthesia (difference in maximum aggregation ranged from 13-29%). During CPB and immediately thereafter, all aggregation variables were significantly reduced in the CABG patients (reduction in maximum aggregation ranged from -32 to -49%) and were significantly different from the platelet aggregation in the AVR patients. Five hours after CPB and on the 1st p.o. day platelet aggregation in the CABG group almost returned to baseline values, however, without reaching the values of the AVR patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449814 TI - Quantitation of the turbulent stress distribution downstream of normal, diseased and artificial aortic valves in humans. AB - Damage to blood corpuscles seems to be related to the magnitude and exposure time of the turbulent shear stresses (TSS). According to in vitro studies the critical TSS level for lethal erythrocyte and thrombocyte damage is 150-400 N/m2, for exposure times within physiological ranges. To study the distribution of TSS in the human ascending aorta, a hot-film anemometer needle probe was used to register blood velocities at 41 evenly distributed measuring points in the cross sectional area 5-6 cm downstream of the aortic annulus. Measurements were made in the ascending aorta after normal aortic valves (prior to coronary bypass surgery), after stenotic aortic valves, and after implantation of either St. Jude Medical or Starr Edwards Silastic Ball valves. Three-dimensional visualization of velocity profiles were performed and Reynolds normal stresses (RNS) were calculated within 50-ms overlapping time windows in systole. By coordinating the mean RNS for each time window and for all 41 measuring points, 2-dimensional color-coded mapping of the RNS distribution was made. Based on the velocity profiles and the RNS distribution a relative blood damage index (RBDI) was calculated to incorporate the magnitude and exposure time for RNS in the entire cross-sectional area into one parameter. Turbulent shear stresses were estimated by using a previously determined correlation equation between RNS and TSS. After normal aortic valves, RNS was below 4 N/m2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1449815 TI - Problems associated with mechanical heart valve sounds. AB - A cross-sectional study of 50 randomly selected patients 12-36 months following mechanical heart valve replacement with Bjork-Shiley tilting disc valves was undertaken to investigate the factors which affect perception of, and reaction to, sounds generated by mechanical heart valves implanted in patients. Numerous problems were generated by the valves, including annoyance (68%), sleep disturbance (52% in patients; and 46% in patients' partners), interference with concentration (36%) and social embarrassment (28%). These findings are not affected by the measured level of sound or any variation in the number or anatomical position of the valve(s), though age and sex do seem to matter, more problems being reported by younger patients and those of the female sex. Aspects of the patient's personality did not seem to alter the difficulties experienced, though a high level of psychological morbidity was identified in the group as a whole. Most patients experience problems due directly to the noise generated by their valve and should be adequately warned of this before operation. This should also be taken into consideration in designing and evaluating new valve prostheses. PMID- 1449816 TI - Aortic valve replacement in cardiac ochronosis. AB - Two patients with generalized ochronosis developed cardiovascular symptoms related to cardiac ochronosis with aortic valvular stenosis. One patient with a transvalvular pressure gradient of 150 mm Hg underwent emergency aortic valve replacement. The other patient with a transvalvular pressure gradient of 96 mm Hg underwent successful elective aortic valve replacement. Cardiac ochronosis is a rare disease that might be encountered, with the typical signs, during an elective, planned cardiac operation. The most frequent presenting feature of this disease seems to be aortic valvular stenosis. PMID- 1449817 TI - Accidental injuries and blood exposure to cardio-thoracic surgical teams. PMID- 1449818 TI - Mouse peritoneal macrophages contain an acylating system specific for twenty carbon polyunsaturated fatty acids. A study with intact cells. AB - It is widely recognized that in addition to regulating the expression and activity of arachidonic acid (AA)-metabolizing enzymes, the availability of free AA limits eicosanoid biosynthesis. AA participates in a deacylation/reacylation cycle of membrane phospholipids in which the fatty acid is cleaved by phospholipase A2 and reesterified by acyltransferase. Thus, free AA can become available either by phospholipase A2 activation or by inhibition of fatty acid reincorporation. We observed that exposure of [3H]AA-prelabeled macrophages to micromolar concentrations of unlabeled AA resulted in a net release of 3H radioactivity into the extracellular medium. This was not the consequence of phospholipase A2 activation, but of impaired reesterification of previously liberated [3H]AA. The eicosanoid precursors eicosatrienoic acid (ETA) and eicosapentaenoic acid (EPA) mimicked the effect of unlabeled AA on 3H radioactivity release from [3H]AA-prelabeled macrophages, but all other fatty acids tested were ineffective. Similarly, only AA, ETA and EPA were able to inhibit [3H]AA uptake by macrophages, all other fatty acids being ineffective. From these data, it is concluded that intact macrophages contain an acylating system specific for the eicosanoid precursors AA, ETA and EPA. Altogether, the results of this study underscore the importance of fatty acid reacylation in controlling free AA levels in macrophages. PMID- 1449819 TI - Lipopolysaccharide priming potentiates calcium ionophore stimulated human placental prostaglandin E2 release in vitro. AB - In this study, the effect of bacterial endotoxin (lipopolysaccharide; LPS) and of LPS priming on the in vitro release of PGE2 from human placental explants was investigated. Both LPS and the calcium ionophore A23187 significantly stimulated PGE2 release (P less than 0.05). Simultaneous exposure of placental explants to both LPS and A23187 revealed no additive or synergistic stimulation of PGE2 release. LPS priming of placental tissue significantly increased A23187 stimulated PGE2 release when compared to non-LPS-primed tissues. The addition of exogenous arachidonic acid (the substrate for PGE2 synthesis) also significantly (P less than 0.05) stimulated PGE2 release. There was, however, no significant further stimulation of PGE2 release following LPS priming in arachidonic acid treated explants. These data suggest that LPS not only increases basal PGE2 release in human placentae, but also potentiates agonist-stimulated PGE2 release, possibly by increasing tissue capacity for endogenous arachidonic acid liberation. PMID- 1449820 TI - Effect of glutathione content on cellular uptake and growth inhibitory activity of prostaglandin A2 in L-1210 cells. AB - Prostaglandin A2 (PGA2) is known to be actively incorporated into mammalian cells and thereby evokes its biological effects. To explore the transport mechanism of PGA2 and the possible role of cellular glutathione (GSH) in the transport process, we prepared GSH-enriched and -depleted L-1210 cells and then incubated with [3H] PGA2. In GSH-depleted cells, the total amount of PGA2 incorporated was reduced to about 50% of that in the control and GSH-enriched cells, accompanied by marked reduction of the PG in the cytosol but not in the nuclei. The kinetics of uptake revealed that the apparent Vmax was reduced by GSH depletion. Subsequent study of L-1210 cells under culture conditions provided similar results; GSH-depletion caused suppression of PG uptake and a reduction in the amount of PGA2 in cytosol, while its nuclear accumulation was little influenced. Comparison of the effect of PGA2 on the growth of control and GSH-depleted cells showed that the PG suppressed cell proliferation to the same extent. Our results suggest that, though uptake of PGA2 may be significantly influenced, its accumulation, and hence the manifestation of its biological effects are not influenced by GSH status. PMID- 1449821 TI - Prostaglandin photoaffinity probes: synthesis and binding affinity of C-18 substituted PGF2 alpha prostanoids bearing a perfluorinated aryl azide. AB - C-18 Phenoxy analogs of prostaglandin F2 alpha (PGF2 alpha) that possessed a perfluorinated aryl azide and an aryl iodide substituent were synthesized and evaluated as potential photoaffinity probes for PGF2 alpha. Prior studies indicated that only hydrophobic modifications in the omega-side chain of PGF2 alpha were compatible with high binding affinity, and this finding excluded the use of a hydroxyl-substituted C-18 phenoxy group as an activated aryl ring capable of radioiodination. Consequently, an alternate means of introducing the iodine substituent using an ipsosubstitution of a trimethylsilyl arene was developed. Although this strategy was successful from a synthetic perspective, the potential PGF2 alpha photoaffinity probe, (15S)-18-[3'-((4''-azido 2'',3'',5'',6''-tetrafluorophenyl)- methoxy) methyl-5'-iodophenoxy]-19,20 bisnorprostaglandin F2 alpha, exhibited only marginal competitive binding with [3H]-PGF2 alpha to ovine luteal cells and to plasma membranes of bovine corpora lutea. The hydrophobic but bulky C-18 substituent was presumably incompatible with effective receptor binding. PMID- 1449822 TI - Prostaglandin photoaffinity probes: synthesis and binding affinity of aryl azide substituted C-1 esters of prostaglandin F2 alpha. AB - In seeking prostaglandin F2 alpha (PGF2 alpha) photoaffinity probes possessing both an efficient, photoactive cross-linking substituent and a radiolabel of high specific activity, the synthesis and binding affinity of PGF2 alpha C-1 esters in which the alcohol component possessed either an aryl azide or a perfluorinated aryl azide was investigated. These derivatives showed great promise due to their ability to compete for the binding of [3H]-PGF2 alpha in both a luteal membrane binding assay and in a whole luteal cell binding assay. Identification of the C-1 site in PGF2 alpha as a site for modification of the PGF2 alpha molecule with photoactive alcohol derivatives represented a logical step toward the goal of developing a useful PGF2 alpha photoaffinity probe. PMID- 1449823 TI - Platelet signal transduction mechanisms induced by eicosanoids. AB - Platelets are in many ways involved in the pathogenesis of artherosclerosis and the development of coronary heart disease, and play a role in acute myocardial infarction (8). They are also an useful model to study cellular activation mechanisms: their isolation from peripheral venous blood is simple and rapid and their physiological responses such as shape change, aggregation and secretion can be easily measured (10). This chapter is focused on our results on the mechanisms of platelet activation and inhibition induced by eicosanoids. PMID- 1449824 TI - Annexins and phospholipase A2 inhibition. AB - Annexins of human placenta have been purified and characterized. In addition to annexins I to VI and II complex, two novel species of 45 and 68 kDa were obtained. Annexins V and II are most abundant. Phospholipase A2 inhibitory activity of annexin V is low in contrast to that of annexins I to VI, and it is best for annexin II complex. In vitro, annexins bind to liposomes to extents which depend on the type of phospholipid used. This induces liposome aggregation whereby Mix, PI, and PC liposomes preferably aggregate. This hinders PLA2 from its access to the substate. Our data suggest that substrate-depletion by annexins is rather the result of liposome cross-bridging than pure liposome surface coating. PMID- 1449825 TI - LDL receptor-dependent polyunsaturated fatty acid transport and metabolism. AB - It is widely assumed that eicosanoid biosynthesis is initiated by an increase in the intracellular concentration of unesterified arachidonic acid (AA) as a consequence of the activation of cellular phospholipases and/or inhibition of AA reacylation reactions. Here, we describe a mechanism of eicosanoid formation that is entirely dependent on low density lipoprotein (LDL) receptor-mediated delivery of AA to eicosanoid producing target cells. This LDL AA pathway introduces a new regulatory component into the provision of unsaturated fatty acids to mammalian cells. PMID- 1449826 TI - Cleavage of phosphatidylcholine: an additional mechanism for stimulation of macrophage eicosanoid synthesis? AB - Cleavage of phosphatidylcholine (PtdChol) as putative mechanism leading to enhanced eicosanoid synthesis was investigated in mouse peritoneal macrophages. Addition of 12-O-tetradecanoylphorbol 13-acetate (TPA) to intact [3H]choline labelled cells did not enhance radioactivity release above control levels. Membrane-bound PtdChol-specific phospholipase (PL) activity was then measured in a cell-free assay using [3H]choline-labelled membranes as endogenous substrate. Preincubation of macrophages with TPA increased PL activity in a time course resembling the one observed for protein kinase C (PKC) activation. Diacylglycerol (DAG) species derived from PtdChol might therefore serve as additional stimulator of rapid macrophage eicosanoid synthesis via PKC. PMID- 1449827 TI - Prostaglandin 9-ketoreductase from pig and human kidney: purification, properties and identity with human carbonyl reductase. AB - Prostaglandin 9-ketoreductase has been purified to apparent homogeneity from pig and human kidney with an overall yield of 6%. The enzyme has a molecular mass of 34 kDa, it is present as an active monomer in diluted solution and contains approx. 2 equivalents Zn++/mole enzyme. It is stereoselective for the pro(S) hydrogen of NADPH and reduces the prostaglandin 9-keto group to yield 90% prostaglandin F2 alpha and 8% of the beta-form. An extensive study of the catalytic properties was carried out, which leads to the conclusion that the enzyme function in vivo is unlikely a catalysis of oxidation/reduction at the prostaglandin 9-position. Five peptides from the pig kidney enzyme were sequenced and compared with the sequence of carbonyl reductase from human placenta. The identity is > 90% and this, together with the immunological cross-reactivity with human brain carbonyl reductase, most strongly suggests that prostaglandin 9 ketoreductase and carbonyl reductase are the same enzyme. PMID- 1449828 TI - Priming mechanisms and induction of heat shock proteins in human polymorphonuclear granulocytes induced by eicosanoids and cytokines. AB - Priming of human polymorphonuclear granulocytes (PMNs) with cytokines (IL-3, IL 6, TNF-alpha) followed by a subsequent stimulation (FMLP) led to an enhanced polymerization of actin and GTPase-activity which correlated to a loss of ras immunoreactivity and an increased expression of Rab proteins. Furthermore TNF alpha and 12-HETE induced the heat shock proteins (hsp 70 family) in PMNs as was demonstrated by metabolic radiolabeling and Western blotting (anti-hsp 72). This activation of the stress response exerted a protective function towards a subsequent lytic attack by a bacterial cytolysin (leukocidin). PMID- 1449829 TI - The role of prostanoids in pediatric diseases employing mass spectrometric techniques. AB - Urinary excretion rates of primary prostanoids and their metabolites are useful parameters to assess as well renal as systemic prostanoid activity under clinical conditions. Children with renal diseases with systemic involvement, such as Bartter syndrome, renal diabetes insipidus, postobstructive hydronephrosis, and acute renal allograft rejection, have exclusively elevated excretion rates of primary prostanoids. In patients with systemic diseases and additional renal involvement, such as hyperprostaglandin E syndrome and hemolytic uremic syndrome, rates of primary prostanoids and of their metabolites are elevated. In contrast, systemic vascular diseases without renal involvement, such as Henoch-Schonlein purpura and persistent pulmonary hypertension in the newborn, are associated only with increased systemic prostanoid activity indicated by elevated excretion rates of prostanoid metabolites, whereas excretion rates of primary metabolites are in the normal range. PMID- 1449830 TI - The role of leukotriene D4 in septic shock models. AB - Septic shock is a major complication during the treatment of intense care patients. A similar pathologic state can be experimentally induced in rodents by application of endotoxins. There is circumstantial as well as direct evidence for a participation of leukotriene D4 in this experimental multiorgan failure. Due to liver-specific sensitivation by galactosamine endotoxin-induced multiorgan failure can be experimentally transposed to a single organ, i.e. hepatic failure. Data presented here show a participation of the eicosanoid leukotriene D4 in either model of sepsis. We have recently described a cellular system modelling endotoxin-induced hepatic failure. In this system based on the coculture of hepatocytes and nonparenchymal liver cells leukotriene D4 is required for the development of cytotoxicity. It is concluded that the three models share pivotal mechanistic principles and might be used complementary to each other in order to study underlying molecular events. PMID- 1449831 TI - Lipoxygenase inhibitors but not site specific 5-lipoxygenase blockers protect against endotoxic shock and inhibit production of tumor necrosis factor. AB - In the present study it was found that lipoxygenase inhibitors prevent LPS-, but not tumor necrosis factor alpha (TNF alpha)-evoked lethality. The specific 5 lipoxygenase inhibitors (MK-886, CGS-8515) were uneffective in endotoxin-induced shock. The 5-lipoxygenase inhibitors interfered with LTC4 formation in macrophages while they did not affect endotoxin induced TNF alpha-formation, neither in cell cultures nor in mice. The potency of other, less specific lipoxygenase blockers to suppress TNF alpha formation correlated quantitatively with their ability to interfere with 13-HODD synthesis. Based on the fact that a tight correlation exists between inhibition of TNF alpha synthesis and 13-HODD formation, this product might be important for TNF alpha formation. PMID- 1449832 TI - Epidermal derived growth factor stimulates the prostaglandin F2 alpha-synthesis in rabbit luteal cells. AB - Isolated rabbit luteal cells from day 6 and 12 of pseudopregnancy were cultured with hCG, EGF, and EGF together with arachidonic acid (AA) in serum-free culture medium for 96 hours. The hCG stimulation of the progesterone (P) synthesis was more pronounced on day 6 then on day 12. EGF alone did not change significantly the production of either P or PGF2 alpha. AA increased the production of PGF2 alpha on day 6 and 12 significantly (3.9-fold on day 6, P < 0.005; 7-fold on day 12, P < 0.001). AA together with EGF increased the level of PGF2 alpha more pronounced when compared with AA alone (7.2-fold on day 6, P < 0.025; 9.8-fold on day 12, P < 0.05). The progesterone production of the cells remained unchanged during EGF exposure. We conclude that EGF together with AA is able to stimulate the PGF2 alpha biosynthesis in cultured rabbit luteal cells. Therefore, EGF could be relevant as an additional regression factor in rabbits. This mechanism seems to be independent from the progesterone synthesis. PMID- 1449834 TI - Thromboxane as diagnostic tool and therapeutic target in cardiovascular disease. AB - Our studies were first directed to improvements in analytical methodology of thromboxane metabolism in man. These methods were then applied in a variety of clinical settings to better define the clinical spectrum and timecourse of platelet related pathomechanisms. They were also applied in studies aiming at optimized therapeutic interventions. Such biochemical guidelines are essential for the optimal planning of future clinical studies. PMID- 1449833 TI - Endogenous eicosanoids modulate cell growth and the expression of immediate early response genes. AB - Experiments were performed in rat mesangial cells indicating that endogenous non cyclooxygenase metabolites of AA act to modulate the mitogenic response. Irrespective of the mitogen used, metabolism of AA by LO and/or CP 450 influences induction of cell growth and expression of the immediate early response genes c fos and Egr-1. In accordance with other reports (3,4) on the influence of eicosanoids on gene expression, our observations indicate that endogenous eicosanoids may act as intracellular mediators. In the mitogenic response, at least two mechanisms of modulation seem possible: i) AA and its metabolites may act by modulating other 2nd messenger systems or ii) eicosanoids may directly regulate the expression of growth-related genes, e.g. by interacting with a fatty acid response element in the promoter region of respective genes. PMID- 1449835 TI - The role of eicosanoids in reproduction. AB - The central role of eicosanoids in reproduction was studied in areas of important clinical interest. First, their involvement in pregnancy-induced hypertension was investigated. Urine of normotensive and hypertensive pregnant women was analysed for 6-keto-PGF1 alpha, TXB2 and PGE2 by HPLC/RIA. PGE2 and 6-keto-PGF1 alpha excretion was markedly reduced in the preeclamptic subgroup of hypertensive patients during the last two trimesters. A reduced urinary excretion of 6-keto PGF1 alpha, TXB2 and PGE2 was also found in a hypertension animal model (rat). Further, tissue cultures of human placentas, deciduas and fetal membranes from hypertensive pregnancies displayed a reduced prostaglandin production. Secondly, in the same in-vitro model the central role of PGE2 of fetal membrane origin for the beginning or parturition was shown. Thirdly, concerning endometrial function, the enhancement of PGF2 alpha and PGE2 formation in secretory endometrial cells by estradiol-17 beta and progesterone was documented. Fourthly, lipoxygenase product content in peritoneal fluid of endometriotic patients did not differ from controls. PMID- 1449836 TI - [The sunset of psychiatry]. PMID- 1449837 TI - [Biologic markers in multiple sclerosis (I). Clinical correlations]. AB - Seven biological markers were studied in a population of 236 patients (144 females, 92 males) with multiple sclerosis as was the relation with the different degrees of diagnostic certainty (Rose and Poser scales), the time of evolution and number of bouts of the disease. The IgG concentrations, IgG ratio and the quantification of the intrathecal IgG synthesis by the Tourtellotte formula isolatedly constituted the most sensitive biological markers for the diagnosis of multiple sclerosis. Altogether, the determination of the number of cells, IgG and the IgG ratio achieved diagnostic sensitivity of 94% for defined multiple sclerosis. The IgG ratio was the most closely related biological marker related with the number of bouts and the time of evolution of the disease. PMID- 1449838 TI - [Biologic markers in multiple sclerosis (and II). Neurophysiologic and imaging correlations]. AB - The relation between the results of 7 biological markers (cells, total protein, albumin, IgG, IgG ratio, Tibbling ratio, and Tourtellotte's formula) and 4 paraclinical tests (PEV, PEATC, CT and MR) in 236 patients with multiple sclerosis (MS) not selected by the localization of symptoms were studied. One hundred forty-one had clinically defined MS, 22 had defined MS supported by a laboratory and 68 had clinically probable MS. The existence of a relation between PEV and MRI abnormality and the increase in the concentration and the ratios of intrathecal IgG synthesis and the degree of certainty of disease diagnosis was demonstrated. The most sensitive test was MRI (93%) followed by VEP (83%) and BAEP (60%) and the sensitivity of the study with high resolution CT including 59 patients explored by double enhancement and delayed cut off was very low (33%). It was considered that for the lack of a specific diagnostic test the use of biological markers PEV and MR constituted a necessary aid in the diagnosis of MS. PMID- 1449839 TI - Conferencia Cotzias de 1991 de la Sociedad Espanola de Neurologa. The genetic etiology of Parkinson's disease. A review of the evidence. AB - It has been amply documented that Lewy body PD can occur on genetic basis. The pedigrees described thus far have constantly shown an autosomal dominant pattern of inheritance. It remains to be determined what proportion of PD generally is familial? Accumulating clinical data indicate the proportion is quite large. The clinical data now available confirm the observations and conclusions of Mjones' pioneering study and are most consistent with the hypothesis that PD is an autosomal dominant disorder with reduced penetrance, markedly age-related expression and a broad range of clinical manifestations extending beyond our traditional clinical concepts of PD and including many atypical cases and formes frustes as Mjones had suggested. As a practical matter of research strategy the study of pedigrees offers the most promising approach available today to clarifying the etiology of PD for they make possible DNA linkage-mapping studies in search of gene loci. PMID- 1449840 TI - [Primary intraventricular hemorrhage in a patient with unilateral moyamoya disease]. AB - According to the diagnostic criteria currently in use, the so-called "unilateral" forms of the moyamoya disease, or rather those in which the disorders of the disease itself--such as occlusion of the internal supraclinoid carotid artery or its terminal branches and development of abnormal collateral circulation in the region of the basal ganglia--are only found in one hemisphere and should be considered as "probable" forms of the disease with a much lower incidence than the bilateral or "defined" forms of the same. One patient with a primary intraventricular hemorrhage (PIVH) in whom an occlusion of the right internal carotid artery was angiographically demonstrated and in whom collateral type moyamoya circulation was found as was the presence of an aneurysm in the right coroid territory is presented. The association of PIVH, unilateral moyamoya disease and aneurysm is infrequent in the literature, with the origin of the bleeding, in some cases, having been attributed to rupture of the aneurysm. Since angiographic control was not available in the patient presented it cannot be excluded that the aneurysm was really a pseudoaneurysm therefore being a consequence, rather than a cause, of the arterial rupture. Thus one of the other mechanisms proposed must be invoked to explain the pathogenesis of the PIVH: rupture of a perforating artery or of a microaneurysm located in the subependimary periventricular region. The treatment recommended for these case of PIVH associated to aneurysm is chirurgical if persistence is demonstrated in successive arteriographies. PMID- 1449841 TI - [Chorea of the lower limbs secondary to cavernoma]. PMID- 1449842 TI - [Action myoclonus in a case of general progressive paralysis]. PMID- 1449843 TI - [Subpial siderosis in the differential diagnosis of sporadic olivopontocerebellar atrophy]. PMID- 1449844 TI - [Tropical spastic paraparesis and HTLV-1 infection in Spain]. PMID- 1449845 TI - [Accidental epileptic crises. Importance of drugs and the genetic factor in their presentation]. PMID- 1449846 TI - [Cervical spinal cord infarction caused by the use of epidural morphine]. PMID- 1449847 TI - [Neurophysiologic evaluation in patients with neuro-Behcet]. PMID- 1449848 TI - Lung infection with alginate-producing, mucoid Pseudomonas aeruginosa in cystic fibrosis. AB - Progressive pulmonary insufficiency is the major cause of morbidity and mortality in patients with the inherited disease cystic fibrosis. The basic defect involves a disturbed ion transport across cells, but it is not known how this leads to the airways becoming highly susceptible to recurrent respiratory tract infection with S. aureus, H. influenzae and P. aeruginosa as the dominating pathogens. P. aeruginosa is not a primary pathogen in CF and some degree of lung damage generally has taken place before colonization begins at approximately 10 years of age. Cross-infection occurs and the incidence of P. aeruginosa infection can be reduced by interrupting person-to-person spread. P. aeruginosa infection is a chronic infection that is never permanently eradicated. However, intensive antipseudomonal chemotherapy has contributed to improved survival rates. 90% of patients remain alive more than 10 years after onset of chronic P. aeruginosa and, on an average, they can maintain an almost unchanged lung function during that period. Diagnosis of chronic infection rests on bacteriological examination and demonstration of a specific antibody response. Immunological assays to detect an early antibody response were developed. It is characteristic, but not specific for CF, that chronic lung infection is caused by alginate producing mucoid P. aeruginosa. Alginate biosynthesis is under complex genetic control and possibly regulated by environmental factors. Alginate was purified from mucoid P. aeruginosa and characterized and it was shown to be immunologically heterogenous. It is generally assumed that the infection begins with strains that are nonmucoid, but serological analysis show that these strains probably also produce the mucoid substance, alginate, in vivo. Patients infected with mucoid strains demonstrate a significantly higher antibody response to all P. aeruginosa antigens and have a lower lung function when compared to patients infected with nonmucoid strains. Despite the pronounced humoral antibody response efficient immune clearance of P. aeruginosa does not occur. Mucoid P. aeruginosa are organisms that are deficient in most of the classical virulence factors. In vivo it grows in a protected biofilm as mucoid microcolonies, where bacteria are enmeshed in a loosely bound, highly hydrated extracellular matrix of alginate. Purified alginate was shown to inhibit chemotaxis of neutrophil leukocytes and unable to activate complement. A deficient SIgA antibody response to alginate has been observed in bronchial secretions and it was hypothesized to be associated with the epithelial transport defect.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1449850 TI - What more do we have to do? PMID- 1449849 TI - Safety in radiation. PMID- 1449851 TI - What more do we have to do? PMID- 1449852 TI - 'Oral infections in the immunocompromised patient'. PMID- 1449853 TI - 'Dental care of patients susceptible to infective endocarditis'. PMID- 1449854 TI - 'Permanent damage to inferior alveolar and lingual nerves'. PMID- 1449855 TI - Wild oat sowing. PMID- 1449856 TI - Diagnostic accuracy and observer performance in the diagnosis of abnormalities in the anterior maxilla: a comparison of panoramic with intraoral radiography. AB - An investigation was undertaken to assess the reliability of radiographic diagnosis of abnormalities of orthodontic significance in the anterior region of the maxilla from intraoral and dental panoramic tomograph (DPT) views. DPT films of 200 patients were scrutinised by two observers on two separate occasions, who also examined intraoral radiographs of the same patients. Sixty-three of these patients were selected because they had previously been diagnosed as presenting with a defined abnormality of orthodontic relevance, such as supernumerary teeth, absent incisors, etc. The remaining cases had been assessed as depicting normal radiographic appearances. Each radiograph was allocated a unique, randomly selected code number as the only means of identification. It was not possible for the observers to match the DPT to the corresponding intraoral films, and this information was only available to the principal investigator (JWF). Both observers were asked to record the presence or otherwise of any abnormalities at each observation of each radiograph, and to record their findings. The overall level of diagnostic accuracy and reproducibility was fairly high, and in general terms the DPT views were as reliable as the intraoral films with regard to the detection of abnormalities; however, there were significant differences between the observers. It was concluded that in many instances supplementary intraoral films would not contribute any additional information compared to the DPT and that selection criteria should be defined for the former. PMID- 1449857 TI - Permanent retention in orthodontic patients with reduced levels of bone support: a pin stabilised resin bonded splint. AB - Bone loss resulting from periodontal disease can precipitate spontaneous tooth migration. Teeth repositioned by orthodontic means are frequently inherently unstable and may need to be permanently retained by some form of splint. A new technique for permanent anterior splinting is described. PMID- 1449858 TI - Characterisation of the ultrastructure of glass-ionomer (poly-alkenoate) cement. AB - Set glass-ionomer cements were sectioned with a diamond knife and examined in the transmission electron microscope. Their appearance was in accordance with the theoretical structure of these materials, close examination revealing glass particles surrounded by a siliceous layer set in a hydrogel matrix. The elemental composition of each region was determined by X-ray microanalysis (energy dispersive). The results of microanalysis supported the ultrastructural observations, with ions that originated from the glass particles being detected throughout the matrix of the set cement. It was suggested that the mobility of these ions in the matrix phase was important in determining the biocompatibility and adhesive properties of glass-ionomer cements. PMID- 1449859 TI - Teaching integrated treatment at Newcastle upon Tyne Dental School. AB - This article explains the educational policy decisions that lay behind the development of a teaching and training programme of integrated dentistry at the Dental School at Newcastle upon Tyne. The development and organisation of a specially designed clinic is described. The pattern of work undertaken during the first 2 years of operation is analysed and the means of clinical assessment of this work discussed. PMID- 1449860 TI - Quality development. AB - The problem with improving quality in dental practice is not so much a difficulty with understanding exactly what quality means, but more a lack of clear guidance as to how to take the simple, practical steps to achieving that improvement in the daily pressures of practice life. This article describes Quality Development, a simple and practical method that can be used in general practice to help the dental team achieve the objectives in quality care that are appropriate to them. PMID- 1449861 TI - 'The future of dentistry'. PMID- 1449862 TI - 'The future of dentistry'. PMID- 1449863 TI - 'The hygienist's dilemma'. PMID- 1449864 TI - 'A complication before operation'. PMID- 1449865 TI - 'Future relationships of dentistry and medicine in education and practice'. PMID- 1449866 TI - What are Section 63 and 'approved' courses and how are they organised? AB - Although Section 63 courses for general dental practitioners in the NHS have been running for many years, there seems to be poor understanding of what 'Section 63' means and how it operates. To some extent this is because of the changes which have taken place since it was introduced and the tremendous expansion in postgraduate dental education (and its objectives) in recent years. The introduction of other 'approved' courses and postgraduate education allowances have created further uncertainties. This paper gives an overview of Section 63, the source of the funds, how they are allocated, how they may be used and who is eligible, and outlines details of other 'approved' courses and the various allowances which GDPs can claim in relation to these different categories of courses. PMID- 1449867 TI - Intra-oral carcinoma simulating benign oral disease. AB - Intra-oral carcinoma can present in a variety of ways. Whilst carcinoma classically presents as an irregular, indurated, painless mass or ulcer, it is also recognised as being a great 'mimic' of benign lesions. A series of four cases of intra-oral squamous cell carcinoma is presented in which the initial presentation suggested a lesion of benign or dental origin. Factors which raise the index of suspicion are discussed. PMID- 1449868 TI - Self-inflicted mutilation of the dentition in a schizophrenic patient. AB - A case is presented in which a patient performed mechanical self-mutilation of her dentition during an episode of psychotic illness. The management of this case is described and discussed. PMID- 1449869 TI - Computer-based learning in orthodontics--a hypertext system. AB - The computer hypertext system which is described is being used at Birmingham dental hospital to complement the undergraduate training programme in orthodontics. The system is a database of orthodontic information which can be accessed and read in any order. Text screens are linked to numerous graphic images, many of which are interactive. Associated question routines provide a means for student self assessment. The scores from these routines are used to give feedback on student performance and the efficacy of teaching methods. A strength of the programme is the ease of authoring material for inclusion in the database. PMID- 1449870 TI - Comparison of 12-bit and 8-bit gray scale resolution in MR imaging of the CNS. An ROC analysis. AB - A reduction in gray scale resolution of digital images from 12 to 8 bits per pixel usually means halving the storage space needed for the images. Theoretically, important diagnostic information may be lost in the process. We compared the sensitivity and specificity achieved by 4 radiologists in reading laser-printed films of original 12-bit MR images and cathode ray tube displays of the same images which had been compressed to 8 bits per pixel using a specially developed computer program. Receiver operating characteristic (ROC) curves showed no significant differences between film reading and screen reading. A paired 2 tailed t-test, applied on the data for actually positive cases, showed that the combined, average performance of the reviewers was significantly better at screen reading than at film reading. No such differences were found for actually negative cases. Some individual differences were found, but it is concluded that gray scale resolution of MR images may be reduced from 12 to 8 bits per pixel without any significant reduction in diagnostic information. PMID- 1449871 TI - Ultrasound guided needle biopsy of brain tumors using an automatic sampling instrument. AB - All ultrasound (US) guided needle biopsies of brain tumors performed during an 8 year period were reviewed. Tissue samples were obtained in 112 of 115 biopsy procedures, and a histologic diagnosis was established in 99 cases (88.4%). The rate of major complications was 8.0%. The mortality is similar as in reports on stereotactic and CT-guided biopsy procedures while the morbidity is higher in our material. There are no large series available on US guided intracranial biopsy with adequate reports of complications. A modified biopsy technique is introduced here using a cutting needle and an automatic sampling instrument. The modified technique, which has been used in all cases since 1985, yielded diagnostic material in 91.5%. This method consistently provides a tissue core which is essential for a confident histopathologic diagnosis. PMID- 1449872 TI - CT and MR imaging of primary tumors of the masticator space. AB - A retrospective study of CT and MR examinations in 14 patients with benign and malignant tumors originating in the masticator space is presented. At presentation, 12 patients revealed tumor extension to adjacent regions and spaces. Perineural tumor spread along trigeminal nerve branches to the cavernous sinus and orbits was combined with facial pain, and/or numbness, ophthalmoplegia, and exophthalmus. Detailed analysis of tumor growth and spread, enhancement and signal features at CT and MR imaging indicated the tumor histology was, with a few exceptions, nonspecific. More extensive growth and bone destruction was noted only among malignant tumors. MR imaging was found superior to CT in delineating tumor extension due to better soft tissue contrast resolution and multiplanar imaging. Posttreatment examinations were available in 11 patients and showed long standing regional edema of the adjacent temporal lobe and masticator muscles in 4 out of 5 patients without clinical evidence of tumor. In 6 patients, CT and MR features were found almost unchanged with only small size differences after various forms of treatment. PMID- 1449873 TI - Comparison of CT findings in non-Hodgkin lymphoma and squamous cell carcinoma of the maxillary sinus. AB - The findings at CT in 11 patients with primary non-Hodgkin lymphoma (NHL) of the maxillary sinus were compared with the CT findings in 21 patients with squamous cell carcinoma (SCC) of the maxillary sinus. In NHL, the segmental bone destruction was in alignment with the bony wall with a massive tumor infiltration into the neighboring structures. In contrast, all patients with SCC were characterized by a soft tissue mass with aggressive bone destruction. About half of the patients with NHL had cervical lymphadenopathy. Post-treatment recalcification of previous bone destruction was seen in 4 out of 5 NHL patients on follow-up CT. In the patients with SCC, only a few had metastatic lymphadenopathy, and no recalcification occurred after treatment. CT is therefore of importance in differentiating NHL from SCC of the maxillary sinus. PMID- 1449874 TI - Large vein sampling for intact parathyroid hormone in preoperative localization of enlarged parathyroid glands. AB - Unilateral neck exploration for primary hyperparathyroidism (pHPT) of old and high risk patients can be safely performed under local anesthesia, provided there is a correct preoperative side localization of the enlarged parathyroid gland. We performed large vein sampling and measured intact parathyroid hormones (PTH) with a new, highly sensitive immunoradiometric assay. The method was used before operation in 20 patients with pHPT. A unilateral positive gradient of serum PTH levels was obtained in 15 patients. At surgery, 13 of these (87%) proved to be correct, i.e., the adenoma was localized on the same side. Thus, the technique correctly lateralized the parathyroid adenoma in 65% of the patients. We conclude that large vein sampling with measurement of intact PTH is a potentially useful investigation for preoperative side localization of parathyroid adenomas in pHPT patients scheduled for unilateral surgery under local anesthesia. However, prior to routine bilateral neck exploration large vein sampling is not justified. PMID- 1449875 TI - Intravascular ultrasonographic appearance of angiographically normal arteries related to age and the occurrence of vascular disease. AB - In 22 individuals (mean age 52 years) the ultrasonographic images of arteries defined as normal by arteriography were studied and related to the age and medical history of the patients. The series was divided into 2 groups: patients with clinical manifestation of atherosclerosis and patients without a history of arterial disease. The study included 6 young patients (mean age 14 years) referred for angiographic documentation of abolished intracranial circulation. A typical 3-layered appearance of the arterial wall was found in young healthy individuals as well as in adult and elderly subjects. There was no difference in the ultrasonographic appearance of muscular and elastic arteries. In patients with extensive obstructive atherosclerosis affecting other parts of the arterial tree, a segment of the iliac artery can have the same appearance as seen in young healthy individuals. There are indications that severe hypertension can result in a thickening of the middle low-echogenic layer of the arterial wall. In patients with chronic renal insufficiency, small calcifications in the middle layer were a typical finding. PMID- 1449876 TI - Holmium:YAG laser angioplasty. Experimental ablation of vascular tissue via flexible ring catheters. AB - This experimental study was designed to define the potential value of a mid infrared holmium laser in the free running mode for angioplasty. Immediately after removal, fresh normal and diseased human cadaveric arteries were irradiated under saline with a Ho:YAG laser (wavelength 2.13 microns). The laser was pulsed at 3 Hz, 250 microseconds pulse width and fluences of 10 to 40 J/cm2. The laser beam was coupled to ring catheters with multiple low-OH quartz fibers. The tip of the delivery device was held in direct contact with the vessel surface with the laser beam oriented perpendicularly. Ablation of atherosclerotic plaque was accomplished at an ablation threshold of 10 J/cm2. The ablation rate was 2.1 to 8.3 microns/pulse. Removal of calcified plaque was only partially effective. There were marked thermal effects with vacuolizations extending up to 1505 +/- 178 microns into the adjacent tissue. Laser light at the mid-infrared wavelength of 2.13 microns is supposed to be attractive as it is readily absorbed in water and can easily be transmitted through optical fibers. However, Q-switching seems to be essential to minimize thermal side effects and to make effective ablation of calcium possible. PMID- 1449877 TI - Visual interpretation compared with caliper and computerized measurements in experimental vessel stenosis. AB - To explain visual interpretation errors on angiograms, visual interpretation, caliper measurement, and computerized measurement of cine film were compared using each of 10 graphic models and 10 acrylic models with "stenotic vessels". Stenosis > 40% was overestimated and stenosis < 40% underestimated by visual interpretation. In caliper measurement, stenosis > 40% at exposure of 90 kV was greatly overestimated by a degree similar to the estimation by visual interpretation, and stenosis > 40% at exposures of 74 kV and 58 kV was slightly overestimated. In computerized measurement, the estimation was consistent with the actual degree of stenosis. Therefore, visual interpretation was not reliable for estimation, and computerized measurement was indispensable for estimation of vessel stenosis. Moreover, we consider the most common cause of error in visual interpretation to be optical illusions. PMID- 1449878 TI - Diagnosis of tracheal carcinoma at chest radiography. AB - All of the 95 primary tracheal carcinomas registered in Finland during 1967 to 1985 were reviewed. Chest radiographs of 44 patients were available. A tracheal tumor was detected in 8 cases (18%) in the primary examination and according to the review all the detected tumors were larger than 15 mm. However, when the same radiographs were reexamined by a senior radiologist, the tumor was identified in the correct site in 66%. This percentage parallels the results of high kV tracheal radiography (69%) performed on 32 patients. Tumors involving anterior or posterior wall and tumors near the bifurcation were the most difficult to detect. PMID- 1449879 TI - High resolution CT in children with cystic fibrosis. AB - High resolution CT (HRCT) was performed in 24 children (median age 57.9 months) suffering from cystic fibrosis (CF). In 23 patients (one examination unacceptable because of motion artifacts) the most frequent finding was bronchial wall thickening, shown in 21 patients (91%), followed by bronchiectasis in 15 patients (65%). Less frequent findings were mucus plugging and patchy consolidations, which could be demonstrated in 11 patients each (48%). Findings were classified using a CT scoring system and including only irreversible pulmonary changes; a statistically significant correlation with lung function tests (FEV1/FVC; MEF50) could be established. HRCT to date seems to be the most valuable method to determine extent and severity of lung involvement in children with CF and should therefore be routinely used for the staging of this disease. PMID- 1449880 TI - CT compared to angiography for staging of tumors of the pancreatic head. AB - A retrospective study of 32 patients with malignant tumor of the pancreatic head and ampullary region is presented. The aim of the study was to compare the ability of CT and angiography to evaluate the peripancreatic vessels, and to correlate the results of tumor staging based upon CT criteria to angiographic and surgical findings. In 5 patients (16%) CT disclosed contiguous tumor growth around vessels not discernible at angiography and, in contradiction to previous reports, angiography added no valuable information regarding main vessel involvement. In terms of sensitivity, specificity, and positive predictive value CT was more accurate in predicting unresectable than resectable tumors, the former with a sensitivity of 92% and a specificity and positive predictive value of 100%. PMID- 1449881 TI - Splenic abscess. Imaging and intervention. AB - We reviewed the imaging findings of 14 splenic abscesses in 13 patients. All patients underwent chest radiography, 12 ultrasonography (US), 9 CT, 4 plain abdominal radiography, 2 99mTc-HMPAO leukocyte scan and 2 99mTc-HIG scan. Three patients were treated with percutaneous catheter drainage, and 5 with diagnostic or therapeutic fine-needle aspiration (FNA). At US the abscess was hypoechoic (n = 9), anechoic (n = 2), or anechoic with gas-bubbles (n = 1), or the entire spleen was inhomogeneous with gas-bubbles (n = 1). At CT the abscesses appeared as low density (18-30 HU) lesions with (n = 2) or without (n = 7) gas. In 2 cases 99mTc-HMPAO leukocyte scan, and in one case 99mTc-HIG scan showed an intrasplenic defect, and in one case 99mTc-HIG scan was considered normal. At plain abdominal radiography extraintestinal gas was suggested in 2 patients, and the findings were normal in 2. US-guided FNA confirmed infectious etiology of the lesion in 4 patients, and a necrotic specimen suggested infection in one. One patient was cured with repeated aspirations. Catheter drainage was successful in all 3 patients who underwent the procedure. We conclude that US and CT are accurate in detecting splenic abscesses. Our results in splenic interventions advocate wider use of the procedures. PMID- 1449882 TI - CT evaluation of compensatory renal growth in relation to postnephrectomy time. AB - In 27 patients nephrectomized for renal carcinoma, the compensatory hypertrophy of the remaining kidney was assessed by 72 CT examinations performed one month before and during 32 months after nephrectomy. Kidney size was estimated on CT by multiple measurements of the renal parenchymal thickness. Kidney growth was evaluated by comparing the amount of renal parenchyma before and after contralateral nephrectomy. Renal compensatory hypertrophy varied with postnephrectomy time. Kidney enlargement was 15% in the first 3 months, reached maximum 30% about a year later, and was reduced to 5%, 2 1/2 years postoperatively. PMID- 1449883 TI - Acute renal failure secondary to rhabdomyolysis. MR imaging of the kidney. AB - MR imaging of the kidney was performed in 6 patients with acute renal failure (ARF) secondary to rhabdomyolysis caused by snake bite (n = 4), crush injury (n = 1), and carbon monoxide poisoning (n = 1). A test for urine myoglobin was positive in all 6 patients and MR imaging was done 6 to 18 days after the causative event of the rhabdomyolysis. MR images in all 6 patients showed globular swelling of the kidneys, preserved corticomedullary contrast on T1 weighted images, and obliteration of corticomedullary contrast on T2-weighted images. Unlike other medical renal diseases in which corticomedullary contrast is lost on T1-weighted images, preservation of the corticomedullary contrast on T1 weighted MR images with globular renal swelling was a constant finding in patients with ARF secondary to rhabdomyolysis. PMID- 1449884 TI - MR imaging with STIR technique and air insufflation for local staging of bladder neoplasms. AB - Fifty-six patients with bladder carcinoma were studied with MR imaging for the assessment of the local stage, using the inversion recovery pulse sequence with fat suppression (STIR) with air in the bladder. With this technique images of the inner and the outer parts of the bladder wall were obtained, showing high contrast between the latter and the tumor (tumor/muscle contrast 89.9%). Four tumor stages were recognized: superficial neoplasms (Tis, Ta, and T1), partial wall infiltrating neoplasms (T2); total wall infiltrating neoplasms (T3a, T3b), and neoplasms involving other pelvic organs (T4). MR imaging was compared with histopathologic diagnosis obtained at transurethral resection or cystectomy. True positive diagnosis was obtained in 80.4%; false-positive in 14.3% of cases; false negative in 5.3%. Despite the relatively high incidence of overstaged neoplasms, STIR technique combined with air in the bladder allowed a good accuracy in local staging. PMID- 1449885 TI - MR pelvimetry--a practical alternative. AB - Pelvimetry remains a useful technique as part of the assessment of the term breech pregnancy where vaginal delivery is planned. MR pelvimetry is accurate, well tolerated and shows soft-tissue structures as well as bone. It avoids the potentially carcinogenic effects of ionising radiation and is thought to be completely safe for mother and fetus. A technique of MR pelvimetry is described which uses gradient-echo sequences. This quick, practical method makes minimal inroads into valuable scanning time, and may therefore be considered a potentially cost-effective alternative to conventional pelvimetry. PMID- 1449886 TI - One or two samples for determination of total plasma clearance of a nonionic contrast medium in patients undergoing enhanced CT. AB - Plasma clearance of nonionic iopamidol (300 mg I/ml) was measured in 50 patients in connection with enhanced CT. Before injection of either 50 or 100 ml of the contrast medium, S-creatinine and urine osmolality were measured. Employing Renalyzer PRX 90, the plasma concentration of iodine was determined in blood samples drawn approximately 3 and 4 h after injection of iopamidol. The glomerular filtration rate was calculated by the Renalyzer using 2 different formulas, one requiring only a single sample, and one requiring at least 2 samples (standard). Both the 3- and 4-h single sample values correlated well with the glomerular filtration rate expressed by the standard sample value. The result was independent of whether 50 or 100 ml had been administered and whether or not water soluble contrast medium had been given orally before CT. As could be expected S-creatinine and urine osmolality correlated poorly with the clearance values. It is concluded that in patients receiving either 50 or 100 ml contrast medium for enhanced CT, the glomerular filtration rate can be determined in a single sample as well as with 2 samples taken between 3 and 4 h after contrast medium injection. PMID- 1449887 TI - Comparison of intravenous contrast agents for CT studies in children. AB - One hundred and eighty children undergoing CT examination were randomly allocated to receive meglumine diatrizoate, iohexol, or iopamidol as their i.v. contrast agent. Minor side effects were detected in 85% of children receiving meglumine diatrizoate, in 18% of those receiving iohexol, and in 36% of those receiving iopamidol. Because many of these minor side effects cause patient motion or delay scanning after contrast medium injection, they potentially degrade image quality. These findings are an indication for the use of low osmolarity contrast agents for i.v. use in pediatric CT imaging. PMID- 1449888 TI - Influence of contrast media on single nephron glomerular filtration rate in rat kidney. A comparison between diatrizoate, iohexol, ioxaglate, and iotrolan. AB - The effects of slow (10 min) i.v. infusions of contrast media (CM, 1,600 mg I/kg b.w.) on single nephron glomerular filtration rate (SNGFR) in the rat kidney were investigated using a micropuncture technique. Diatrizoate, iohexol, or ioxaglate did not change SNGFR, although a tendency towards a transient suppression was seen during the infusion phase. Iotrolan infusion, however, decreased SNGFR (p < 0.05) and the value still remained below the control value 25 min after the start of infusion. Iotrolan is a nonionic dimeric CM and has a lower osmotic effect in the tubules than the ionic dimeric CM and the monomeric CM when given in iodine equivalent doses. These characteristics of iotrolan have probably some influence on the depression of SNGFR after iotrolan injection. PMID- 1449890 TI - Motion associated susceptibility artifacts. AB - A bowel labeling agent is important for improving abdominal MR. Besides providing contrast between the bowel and other organs, the contrast agent itself is a potential source of artifacts. The artifacts created by superparamagnetic particles (SPP) subjected to motion have been studied in vitro at 0.5 T, and compared to artifacts created by a paramagnetic compound. Apart from the expected static effects of the SPP, movement induced additional artifacts were seen as signal displacements in the phase-encoding direction. The artifacts were obvious at an iron concentration of 1 mg Fe/ml, barely visible at 0.2 mg Fe/ml, and completely absent at 0.1 mg Fe/ml. Artifacts were also evident with the SPP outside the imaging slice. This further emphasizes the importance of choosing the lowest effective dose when using SPP contrast agents. For the paramagnetic agent, motion propagated artifacts consisted of high and low signal regions in a mosaic pattern. PMID- 1449889 TI - Viscosity of some contemporary contrast media before and after mixing with whole blood. AB - The viscosity of 7 contrast media was measured using a rotational viscometer. When solutions with similar iodine concentrations were compared, the highest viscosities were found for the nonionic dimers iodixanol and iotrolan, the lowest for diatrizoate, iopamidol, and iopromide, and intermediate values for iohexol and ioxaglate. The viscosity of iohexol and ioxaglate was found to vary linearly with temperature and quadratically with concentration. Whole-blood viscosity was measured for 5 subjects at high and low shear rates before and after mixing with contrast media in various proportions. Low-shear viscosity was found to decrease and high-shear viscosity to increase with contrast medium concentration. It is concluded that the contrast media currently used may affect blood rheology less than previous agents, despite their higher viscosity. PMID- 1449891 TI - Iodixanol--a new nonionic dimer--in aortofemoral angiography. AB - In 26 patients iodixanol, a new nonionic dimer, isotonic to blood in all concentrations, was used as contrast medium in aortofemoral angiography. Half of the patients received contrast medium in a concentration of 270 mg I/ml and the other half 320 mg I/ml. The aim of the trial was to evaluate the safety and tolerability of iodixanol and the radiographic efficacy of the two concentrations. The degree of discomfort, adverse events, changes in serum chemistry parameters, and diagnostic information were assessed. There were no changes or trends of clinical importance in serum chemistry parameters. The side effects were mild and consisted mostly of some sensation of warmth of short duration. No other adverse events were seen. The overall radiographic efficacy did not show any significant difference between the two concentrations. This indicates that iodixanol is safe and well tolerated when used in adult femoral angiography. PMID- 1449892 TI - [Homeopathy and research]. PMID- 1449893 TI - [Alternative treatment. Documentation and demand]. PMID- 1449894 TI - ["Alternative nursing"]. PMID- 1449895 TI - [Chinese herbal medicine]. PMID- 1449896 TI - [Current research in medicinal plants]. PMID- 1449898 TI - [Norwegian Nurses' Association's activities with alternative medicine]. PMID- 1449897 TI - [Foot zone therapy]. PMID- 1449899 TI - [Heart-lung resuscitation--duty or choice?]. PMID- 1449900 TI - [Acupuncture for nurses?]. PMID- 1449901 TI - [Patient turnover in homes for the aged and nursing homes]. PMID- 1449902 TI - [New field of work: counseling for the aged and families]. PMID- 1449903 TI - [Priests in the hospital environment]. PMID- 1449904 TI - [Hospice care at home]. PMID- 1449905 TI - [Breast cancer: the difficult waiting time--from diagnosis to treatment]. PMID- 1449906 TI - [Community health services. Program for psychiatric patients in Rogaland 1980 1992]. PMID- 1449907 TI - ["Nursing profession--a paradox?"]. PMID- 1449908 TI - ["Pulpit" in pelvic relaxation]. PMID- 1449909 TI - [Women exposed to incest--consequences for pregnancy and childbirth]. PMID- 1449910 TI - [PhD Degree in breast feeding. Interview by Ingrid S. Stephensen]. PMID- 1449911 TI - [Homeopathy]. PMID- 1449912 TI - The function of the 5-hydroxymethyl group of lactose in enzymatic hydrolysis with beta-galactosidase from E. coli. AB - A series of 6-substituted methyl lactoside derivatives together with methyl allolactoside and (6S)-methyl [6-2H]lactoside have been synthesized and characterized by NMR spectroscopy. All compounds were tested as substrates for the enzyme beta-galactosidase from E. coli using progress curve kinetic methology both in single-substrate and competition experiments. The results show that the hydrolysis of methyl lactoside to a large extent takes place through an intramolecular transglycosidation reaction via allolactoside. Furthermore, methyl 6-amino-6-deoxy-D-glucopyranoside proved to be an ihibitor for the enzymatic hydrolysis. PMID- 1449913 TI - Two-dimensional nuclear Overhauser enhancement NMR experiments on pelargonidin-3 glucopyranoside, an anthocyanin of low molecular mass. AB - Pelargonidin-3-glucoside has been isolated from the acidified methanolic extract of strawberries (Fragaria anannassa variety Corona) by successive application of an ion-exchange resin, droplet-counter chromatography and gel filtration. The pigment in acidified methanolic solution was studied by means of the two dimensional nuclear Overhauser enhancement NMR technique, and the sugar unit was found to be attached to the 3-position on the aglycone. At +20 degrees C the pigment was found to be in the extreme narrowing limit where the NOESY cross peaks are negative. However, at -20 degrees C this low-mass anthocyanin could be studied in the slow motion regime where the NOESY cross-peaks are positive. With a mixing time of 0.3 s, the glucose H1"-H4" proton pair was measured in the initial cross-relaxation rate and their cross-peak volume corresponded to the H1" H4" distance found in a 4C1 chair conformation. PMID- 1449914 TI - How can myocarditis be diagnosed and should it be treated? PMID- 1449915 TI - Answers to complex questions cannot be derived from "simple" trials. PMID- 1449916 TI - Changes in left ventricular function and wall thickness in heart transplant recipients and their relation to acute rejection: an assessment by digitised M mode echocardiography. AB - OBJECTIVE: Assessment of changes in left ventricular diastolic function and wall thickness after heart transplantation to verify whether these changes predicted acute rejection assessed by endomyocardial biopsy. DESIGN: Follow up according to a predefined protocol of consecutive patients from the first week after transplantation. SETTING: Heart transplantation unit of the Thoraxcentre, University Hospital Rotterdam Dijkzigt, The Netherlands. PATIENTS: All 32 patients undergoing orthotopic heart transplantation from 1 January 1989 to 31 March 1990 were examined. Two were excluded from the analysis. Patients were treated with cyclosporin and low dose steroids. MAIN OUTCOME MEASURES: Data obtained by digitised M mode echocardiography were compared with the results of endomyocardial biopsy (Billingham classification). Mean values for left ventricular wall thickness, internal dimension, and their standardised rates of change and fractional shortening were determined from 4-6 consecutive expiratory beats. Mean values and individual trends during follow up were also investigated for each ultrasound variable. The results of these average values were compared with values in a group of 10 healthy volunteers. RESULTS: Median follow-up was 177 days (range 10-399). Two hundred and sixty three consecutive M mode studies were examined in relation to concurrent biopsy results. No significant differences were observed between the ultrasound variables at the time of moderate acute rejection (Billingham class 2, n = 37) and other biopsy classes (n = 226). Nor did changes in individual patients predict (moderate) acute rejection episodes. Twenty six of the 30 patients had an abnormal (slow) left ventricular relaxation pattern throughout follow up. CONCLUSIONS: Digitised left ventricular M mode echocardiography did not predict the presence of acute rejection. In most patients there was a persistent slow left ventricular relaxation pattern. PMID- 1449917 TI - Fall in pulmonary vascular resistance in patients awaiting heart transplantation. AB - BACKGROUND: Raised pulmonary vascular resistance is associated with decreased survival after orthotopic heart transplantation and patients with this risk factor are usually denied transplantation. In a proportion of cases raised pulmonary vascular resistance may fall with time and medical treatment. METHODS: Seven patients with high pulmonary vascular resistance (range 3.9-6.6 Wood units) at initial assessment for cardiac transplantation were restudied by right heart catheterisation after a period of seven to 17 months. RESULTS: In five of the seven patients the pulmonary vascular resistance had fallen, allowing orthotopic heart transplantation to be performed in four. In one patient the resistance was static and in one it had risen. The mean fall in pulmonary vascular resistance for the group was (mean (SD)) 2.6 (2.7) Wood units, p < 0.05. CONCLUSION: Patients who have been denied transplantation on the basis of their raised pulmonary vascular resistance should be reassessed after four to six months if they remain otherwise clinically suitable. PMID- 1449918 TI - Early vasodilator treatment in myocardial infarction: appropriate for the majority or minority? AB - OBJECTIVE: To assess the influence of vasodilator treatment started early after myocardial infarction on left ventricular size and function. SETTING: Coronary care unit, Royal Infirmary, Edinburgh. PATIENTS: 105 patients with acute myocardial infarction (systolic blood pressure > 90 mm Hg) were randomised within 24 hours of the start of pain. Unlike previous studies 88% of the patients received thrombolysis. METHODS: Double blind randomised placebo controlled study with either 12.5 mg of captopril three times daily or 20 mg of isosorbide mononitrate three times daily for 28 days. MAIN OUTCOME MEASURES: Clinical outcome and left ventricular size and function assessed by echocardiography, radionuclide ventriculography, and magnetic resonance imaging. RESULTS: There was no difference in left ventricular size or function in either treatment group as measured one week after the end of the trial. Even the placebo group tended to decrease left ventricular diameter over the four week study period (one week: 5.0 (0.1) v, five weeks: 4.8 (0.1) cm, NS). Four patients had an adverse clinical outcome in the placebo group whereas no adverse outcome was seen in the captopril group. CONCLUSIONS: Vasodilator treatment may be of limited value or of no benefit for most infarct patients, particularly those treated with thrombolytic agents. Captopril, however, may benefit patients at high risk. PMID- 1449919 TI - Evidence of increased platelet activation after thrombolysis in patients with acute myocardial infarction. AB - OBJECTIVE: To assess platelet activation after thrombolysis in patients with acute myocardial infarction. DESIGN: Platelet function was assessed by measurement of the in vivo synthesis of thromboxane by gas chromatography-mass spectrometry of thromboxane's major urinary metabolite, 2,3-dinor-thromboxane-B2. SETTING: Coronary care unit of Huddinge University Hospital. SUBJECTS: 30 patients with acute myocardial infarction given either streptokinase 1.5 million units intravenously over one hour + 500 mg aspirin (n = 10), 500 mg aspirin (n = 10), or neither thrombolysis nor aspirin (n = 10). RESULTS: Patients treated by thrombolysis had a 20-fold increase in thromboxane formation during thrombolysis compared with control patients not treated by thrombolysis (p = 0.0001). Until two days after thrombolysis thromboxane production in patients treated with streptokinase did not decrease to a value comparable with patients treated with aspirin but not given thrombolysis. CONCLUSION: Thromboxane production increased considerably during thrombolysis, possibly reflecting greatly enhanced platelet activation. The slow decrease in thromboxane formation after treatment with aspirin suggests that the efficacy of thrombolysis might be improved by more efficient antiplatelet treatment. PMID- 1449920 TI - Left atrial and left ventricular diastolic function during acute myocardial ischaemia. AB - OBJECTIVE: To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia. DESIGN: Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery. PATIENTS: 20 patients with isolated disease of the left anterior descending artery and normal left ventricular function. RESULTS: The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by -37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by -11%). CONCLUSIONS: Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia. PMID- 1449921 TI - Nocturnal hypoxia and arrhythmias in patients with impaired left ventricular function. AB - OBJECTIVES: To document the incidence of hypoxic episodes in a series of patients with impaired left ventricular function, and to correlate the occurrence of hypoxia with severity of arrhythmia. PATIENTS: 34 patients with breathlessness and clinical evidence of left ventricular dysfunction. MAIN OUTCOME MEASURES: Simultaneous overnight finger oximetry and electrocardiographic monitoring. RESULTS: High grade arrhythmias (Lown grade > III) occurred in 20/34 (59%) of patients, and frequent dips in oxygen saturation were noticed (mean dip frequency 4.8/h, range 0.1-20.0). 20/34 (59%) of patients had episodic hypoxaemia, including 13/34 (38%) with a classical Cheyne Stokes pattern. There was a correlation between dip frequency and the presence of high grade arrhythmias (those with high grade arrhythmia had mean (SD) 6.7 (5.5) dips/h v 2.2 (3.4) in those without, p < 0.01); there was also a correlation between the presence of arrhythmias and episodic hypoxaemia (episodic hypoxaemia in those with high grade arrhythmias occurred in 17/20 (85%) v 3/14 (21%) of those without arrhythmias, p < 0.002). There was no correlation between the presence of high grade arrhythmias or dip frequency and the extent of left ventricular impairment, which was present in all patients (mean (SD) ejection fraction 26% (13%)). CONCLUSION: Noticeable abnormalities of nocturnal oxygen saturation occur in patients with impaired left ventricular function, and these are associated with high grade arrhythmias. Interventions that limit desaturation may have valuable anti-arrhythmic effects. PMID- 1449922 TI - Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after inhibition of neutral endopeptidase: effects on diastolic function. AB - OBJECTIVE: +/- Candoxatrilat was used to raise atrial natriuretic factor (ANF) concentrations in patients with heart failure, and the effects on left ventricular systolic and diastolic function were studied to determine the contribution of peripheral and central mechanisms to the haemodynamic effects. DESIGN: This was a single blind, randomised comparison of +/- candoxatrilat and placebo in patients with mild heart failure. All patients received two intravenous doses of +/- candoxatrilat and two placebo doses on four consecutive days. SETTING: A teaching hospital department of cardiology. PATIENTS: Six men (mean age 52 years) with mild heart failure (New York Heart Association class II) due to ischaemic heart disease (four patients) or dilated cardiomyopathy (two patients) were included. Mean ejection fraction was 37.5% and mean peak oxygen consumption was 20.4 ml/min/kg. MAIN OUTCOME MEASURES: Plasma ANF concentrations, haemodynamic indices and left ventricular diastolic function measured by early to atrial filling rate (E:A ratio) with Doppler echocardiography were determined before and after +/- candoxatrilat and placebo. RESULTS: +/- Candoxatrilat caused a threefold rise of plasma ANF compared with placebo (p < 0.005), but there was no significant change in heart rate, blood pressure, or cardiac output. Mean right atrial pressure fell from 6.7 to 4.7 mmHg (NS) and pulmonary artery wedge pressure fell from 9.2 to 6.7 mmHg (p < 0.05). Doppler echocardiographic measurements of transmitral blood flow showed a significant fall in peak early left ventricular filling velocity from 39.5 to 34.2 cm/s (p < 0.05), along with a non-significant rise in peak atrial filling velocity from 39.7-41.6 cm/s after +/ candoxatrilat. The E:A ratio, a Doppler index of left ventricular diastolic function, fell from a mean of 1.04 to 0.87 (p < 0.05). CONCLUSIONS: +/- Candoxatrilat increased plasma ANF concentrations and reduced right atrial and pulmonary artery wedge pressures. No evidence of an improvement in left ventricular systolic or diastolic function was found, so the fall in preload was due to peripheral effects, either an increase in venous capacitance or a fall in circulating blood volume. PMID- 1449923 TI - Efficacy of flecainide, sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality. AB - OBJECTIVE: A comparison of the efficacy of verapamil, sotalol, and flecainide to suppress right ventricular tachycardia (VT) in patients with a clinically normal heart. DESIGN: Patients underwent treatment serially with verapamil (360 mg daily), sotalol (240 or 320 mg daily), and flecainide (200 or 300 mg daily), (the larger dose was for patients heavier than 80 kg) to suppress tachycardia. Each drug was given orally for five half lives before testing. PATIENTS: 23 patients with right VT associated with a clinically normal heart were studied. OUTCOME MEASURES: The effects of drug treatment were examined by the number of ventricular events on 24 hour Holter monitoring, and the ability of tachycardia to be induced by treadmill exercise testing (Bruce protocol) and programmed ventricular stimulation (Wellens protocol), compared with drug free baseline tests. SETTING: Patients were studied in a tertiary referral centre. RESULTS: All three drugs suppressed ventricular salvos (> 3, < 5 consecutive ventricular premature contractions) (p < 0.01) and VT (p < 0.05) on Holter monitoring and did not differ statistically in effect. Exercise induced VT was also suppressed by all three drugs (p < 0.01), and of these sotalol was the most effective although this was not statistically significant (14/23 inducible when drug free, 4/23 on flecainide, 2/23 on sotalol, 5/23 on verapamil). Sustained and non-sustained VT induced by programmed stimulation was also suppressed by the three drugs (p < 0.01) and again sotalol was the best of these though the differences did not achieve statistical significance (17/23 inducible when drug free, 4/17 on flecainide, 2/17 on sotalol, and 6/17 on verapamil). Proarrhythmic effects of drugs were found in a few patients. There was no difference in the efficacy of the drugs in patients with histological abnormalities of the myocardium when compared with those of normal histology. CONCLUSIONS: Ventricular tachycardia associated with a clinically normal heart can be suppressed by flecainide, sotalol, or verapamil. In individual patients sotalol was the most frequently effective drug (effective in > 89% of patients) and is a suitable choice for first line treatment. PMID- 1449924 TI - Comparison of unipolar and bipolar ventricular paced evoked responses. AB - OBJECTIVES: To study the differences between endocardial bipolar and unipolar ventricular paced evoked responses and surface electrocardiograms. PATIENTS: 10 patients with conduction system disease awaiting insertion of a permanent pacemaker were studied with temporary ventricular pacing from the right ventricular apex. MAIN OUTCOME MEASURE: Comparison of the durations of the QRS complexes and QTa and QTe intervals of the endocardial bipolar paced evoked response and the surface electrocardiogram with those of the reference unipolar paced evoked response. RESULTS: By comparison with the unipolar reference, the mean durations of the QRS complexes of the bipolar signal and the surface electrocardiogram were 41.8% and 132.1% respectively. The mean QTa interval was 85.9% and 112.2% respectively and the mean QTe interval was 86.9% and 109.5% respectively. All these differences were significant. The amplitudes of the unipolar QRS complexes and T waves were significantly larger than those recorded in the bipolar configuration. CONCLUSIONS: Differences between the unipolar and bipolar ventricular paced evoked responses are significant. The time course of the unipolar signal is closer to that of the surface electrocardiogram. This indicates that the unipolar paced evoked response does not reflect local electrophysiological events, as has been suggested previously. PMID- 1449926 TI - Mitochondrial DNA deletion diagnosed by analysis of an endomyocardial biopsy specimen from a patient with Kearns-Sayre syndrome and complete heart block. AB - Defects of mitochondrial DNA have been found at necropsy in the myocardium of patients with Kearns-Sayre syndrome. A patient with characteristics typical of Kearns-Sayre syndrome and a complete heart block is described. Southern blot analysis showed a deletion of 3.3 kb in the mitochondrial DNA in an endomyocardial biopsy specimen and in skeletal muscle. The deletion led to the disappearance of the genes for four transfer RNAs and four subunits of complex I (NADH:ubiquinone oxidoreductase) in the mitochondrial respiratory chain. The defect could not be demonstrated in whole blood despite amplification of the mitochondrial DNA region of interest by the polymerase chain reaction technique. There can be heteroplasmy--that is, normal and abnormal mitochondrial DNA populations in one cell--in different tissues, and the degree of heteroplasmy may be crucial in the development of organ-specific symptoms. This patient raises the possibility that some tissues can be specifically enriched with mitochondria with DNA defects and emphasises the need for elective sampling of the target tissue and polymerase chain reaction technique to exclude these defects. The role of mitochondrial DNA defects in idiopathic cardiomyopathies could perhaps be studied by analysis of mitochondrial DNA from endomyocardial biopsy specimens. PMID- 1449925 TI - Effects of abnormal activation on the time course of the left ventricular pressure pulse in dilated cardiomyopathy. AB - OBJECTIVE: To investigate the effects of QRS duration on characteristics of the left ventricular pressure pulse derived from the time course of functional mitral regurgitation by continuous wave Doppler. DESIGN: Retrospective and prospective study of 50 patients with dilated cardiomyopathy, by electrocardiography, echocardiography, and Doppler cardiography. SETTING: Tertiary cardiac referral centre. PATIENTS: 50 patients (mean age (SD) 58 (16)) with dilated cardiomyopathy, all with functional mitral regurgitation. RESULTS: The values of QRS duration ranged widely, from 70 to 190 ms with a mean value of 110 ms, and were unimodally distributed. The overall duration of mitral regurgitation correlated positively with QRS time (r = 0.65) over the entire range of values. When the duration of mitral regurgitation was divided into contraction, aortic ejection, and relaxation times, increased QRS duration prolonged contraction (r = 0.51) and relaxation (r = 0.52) times. Aortic ejection time was affected by RR interval (r = 0.74). Duration of QRS correlated negatively with peak rate of rise in left ventricular pressure (+dP/dt) (r = -0.48), and positively with the time intervals from Q to peak pressure (r = 0.49) and to peak +dP/dt (r = 0.72), and also with those from the start of mitral regurgitation to peak pressure (r = 0.49) and to peak +dP/dt (r = 0.76). Duration of QRS did not directly affect the peak rate of left ventricular pressure fall (-dP/dt), or the isovolumic relaxation period. CONCLUSIONS: Values of QRS duration are unimodally distributed in patients with dilated cardiomyopathy, without evidence of a discrete group of patients with left bundle branch block. Prolonged QRS duration reduces peak +dP/dt, prolongs overall duration of the pressure pulse, the time to peak +dP/dt, and relaxation time. Duration of QRS must therefore be taken into account in assessing standard measurements of myocardial function in patients with dilated cardiomyopathy. PMID- 1449928 TI - A posteroseptal accessory pathway located in a coronary sinus aneurysm: diagnosis and radiofrequency catheter ablation. AB - A coronary sinus aneurysm was diagnosed by means of echocardiography, coronary sinus contrast angiography, coronary angiography, and nuclear magnetic resonance imaging in a patient with Wolff-Parkinson-White syndrome caused by a posteroseptal accessory pathway. Percutaneous radiofrequency current catheter ablation performed in the isthmus of the coronary sinus aneurysm was successful. PMID- 1449927 TI - Apparent obstruction of the superior vena cava and a continuous murmur: signs of a fistula between a vein graft aneurysm and the right atrium. AB - A previously undescribed complication of a saphenous vein aortocoronary bypass graft, namely formation of a fistula between a vein graft aneurysm and the right atrium is reported. A patient presented with a continuous murmur and a combination of signs suggesting superior vena cava obstruction. This pathology was shown by both echocardiography and angiography. Surgical treatment was attempted. PMID- 1449930 TI - Effect of increasing heart rate on Doppler indices of left ventricular performance in healthy men. AB - OBJECTIVE: To investigate the effects of heart rate on the Doppler measurements of left ventricular function and to determine the normal pattern of rate dependency. SETTING: University hospital specialising in internal medicine. PARTICIPANTS: 14 healthy male volunteers 10 of whom were studied. INTERVENTION: Transoesophageal atrial pacing. MAIN OUTCOME MEASURES: At paced rates of 70, 80, and 90 ppm the ratio of early to late peak transmitral flow velocity (E/A) was 1.97 (0.28), 1.49 (0.21), and 0.95 (0.11) respectively; the ratio of early to late time-velocity integrals of transmitral flow (Ei/Ai) was 3.03 (0.51), 2.11 (0.24), and 1.14 (0.30) respectively; and the atrial filling fraction (AFF) was 0.17 (0.03), 0.21, (0.04), and 0.24 (0.04) (mean (SD)). RESULTS: Heart rate showed a linear correlation with E/A (r2 = 0.806), Ei/Ai (r2 = 0.838), and AFF (r2 = 0.343). Neither the peak aortic flow velocity or the mean aortic flow acceleration showed significant changes during pacing at rates of 70, 80, 90, and 100 ppm. CONCLUSIONS: E/A and Ei/Ai can be expected to decrease by 0.5 and 0.9 for each increase of 10 beats/min in heart rate. Knowledge of this relation may be useful for the development of algorithms to correct for heart rate when diastolic function is assessed. PMID- 1449929 TI - Restenosis after coronary angioplasty: a proposal of new comparative approaches based on quantitative angiography. PMID- 1449931 TI - Cardiac surgery: moving away from intensive care. AB - OBJECTIVE: To evaluate outcome in patients managed outside an intensive care unit after open heart surgery. BACKGROUND: The high cost of cardiac surgery is mainly due to the needs of traditional postoperative care. The requirements for intensive care and treatment has decreased with improvements in techniques of cardiac surgery and anaesthesia. In this setting the need to continue to depend on intensive care units for the recovery of cardiac surgical patients is questionable on clinical and economic grounds. DESIGN: Postoperative outcome in 245 patients over a four month period was studied prospectively. PATIENTS: Mean age of the patients was 63.2 years. They underwent a wide variety of operative procedures. Ninety percent of them recovered in a dedicated three bed cardiac surgical recovery area where the management protocol led to rapid extubation and step down in dependency care. RESULTS: Median time for ventilatory support was 90 minutes after transfer to the area. Only five patients were subsequently admitted to the general intensive care unit for prolonged respiratory and cardiac support. Ten patients were electively admitted to the general intensive care unit. Two deaths occurred in hospital in this group (0.8%). Four patients were ventilated for 24 hours in the recovery area itself and made an uncomplicated recovery. CONCLUSION: This study confirms that over 90% of patients undergoing cardiac surgery would recover safely and be treated effectively in a more economical area than intensive care. PMID- 1449932 TI - Cardiac interventional procedure in the United Kingdom during 1990. The British Cardiovascular Intervention Society. PMID- 1449933 TI - Guidelines for training in percutaneous transluminal coronary angioplasty (PTCA). Report of The Council of the British Cardiovascular Intervention Society (BCIS). PMID- 1449934 TI - Simple bone cysts. A review of 59 cases with special reference to their treatment. AB - In a retrospective study, 21 simple bone cysts (SBC) treated by curettage (with or without bone grafting) are compared to 20 SBC treated by intralesional injections of methylprednisolone. Curettage led to 43% favourable results and 29% recurrences. Cortisone injections led to 90% favourable results and 5% recurrences. Combined therapy (curettage and injections) led to results comparable to injections only. In our experience, curettage and hydroxyapatite grafting led to 100% complete healing (only 2 cases). We recommend intralesional methylprednisolone injections because the method is easy, effective and safe. PMID- 1449935 TI - Effect of cup geometry and the presence of cement on acetabular component fixation. AB - Two series of implanted conical, polyethylene Ring cups were studied clinically and radiographically. In one series the cups were uncemented while in the second cement was used. The results using cemented conical cups were then compared with results using a cemented cup of hemispherical design to study the effect of cup geometry. At 7-8 years a total of 3.8% of the cemented conical series and 2.9% of the uncemented were revised for aseptic loosening. At 9 years survivorship was identical. Migration of the sockets occurred in approximately 25% of both series and was directly related to cup cover of less than 80% (P < 0.001). The series of cemented hemispherical cups were reviewed after an identical period. Although the numbers revised for loosening were comparable in this and the cemented conical group, radiological migration was statistically greater in the latter (P < 0.001). Alternative methods of socket preparation and cement technique were thought to be the most likely explanation for the observed differences. PMID- 1449936 TI - Clinical results and radiologic findings after cementless implantation of PCA stems in total hip replacement. AB - The results of radiologic and clinical follow-up of 81 PCA (porous coated anatomie) hip joint prostheses implanted in our clinic between 1986 and 1988 are presented. One of the prostheses had to be explanted because of aseptic loosening after 2.5 years' implantation. Contrary to the fixation concept of the prosthesis, which requires both proximal osseointegration and free axial shifting of the distal part of the prosthesis, our follow-up radiographs showed proximal lysis of 2 mm and more as well as distal hypersclerosis of 3 mm and more in the form of endosteal bone formation in 70% of cases 3 years after implantation. On the basis of our data, the question whether these bone reactions will finally lead to aseptic loosening of the implant cannot be answered yet. PMID- 1449937 TI - The modified Mayo procedure combined with basal valgus osteotomy of the first metatarsal for severe hallux valgus. AB - The modified Mayo procedure corrects valgus deformity of the great toe secondary to osteoarthritis in the first metatarsophalangeal joint. Basal osteotomy of the first metatarsal to correct metatarsus primus varus and to maintain correction of the valgus deformity may be performed simultaneously. We retrospectively reviewed the results in 55 of 70 feet treated by this combined procedure. The average duration of follow-up was 4.2 years (range 0.5-6 years) and the average age at operation was 63 years (range 45-80 years). The results were either very good or good in 82%, moderate in 14%, and poor in 4%. Our technique of basal osteotomy of the first metatarsal is a simple and effective procedure to correct metatarsus primus varus and may restore the distal transverse arch. It should be considered as a possible method of treatment when the intermetatarsal angle is greater than 10 degrees. PMID- 1449938 TI - The pelvic compartment syndrome. AB - In the pelvic region three major compartments (gluteus medius-minimus compartment, gluteus maximus compartment, and iliopsoas compartment) can be distinguished from the smaller compartment of the tensor fasciae latae muscle. Pelvic compartment syndromes are rare. A clear history of trauma is often lacking. Association with drug and alcohol abuse is common, as is the association with the widespread use of anticoagulant therapy. From 1982 to 1990 six patients with acute buttock compartment syndrome were treated in the Department of Trauma Surgery of Hannover Medical School. In five patients fasciotomy of the gluteal compartment was performed. Two patients with a compartment syndrome secondary to necrotizing fasciitis died of septic multiple organ failure. The mean follow-up of the four other patients was 29 months (7-48 months). Three of these four patients revealed a decrease of gluteal muscle volume. Ergometric tests showed a decrease in gluteal muscle force in all patients. PMID- 1449939 TI - Aneurysmal bone cyst. A review of 52 primary and 16 secondary cases. AB - Authors report on the results of treatment of 52 primary and 16 secondary aneurysmal bone cysts (ABC). ABC grow rapidly; 84% of them have already destroyed more than the half of the bone width at recognition. En bloc resection is preferred when the ABC is growing superficially and eccentrically and more than half of the bone width is intact. Careful curettage and bone grafting still remains the surgical method of choice in the majority of cases, when the ABC is more destructive and affects the subchondral bone of the joints. Segmental resection is only indicated when removal of the affected bone does not influence the function of the extremity. Superselective embolization of the cyst was performed in seven cases with excellent results. This method is suggested for ABC in certain locations inaccessible to surgical intervention, e.g., the pelvis, or to avoid excessive bleeding in hypervascularized tumors. In one case, however, an incomplete rebuilding of the ABC could only be achieved by the administration of calcitonin. The 16 cases of secondary ABC were observed mostly in association with osteoblastomas, giant-cell tumors, and osteosarcomas. The incidence of the secondary ABC was 23% in the whole ABC group but not more than 2-4% among the osteosarcomas and giant-cell tumors. Secondary ABC may confuse the histological and clinical diagnoses and that, especially in cases of osteosarcoma, may have fatal consequences. PMID- 1449940 TI - Diagnosis and treatment of retroperitoneal hematoma in multiple trauma patients. AB - From 1984 to 1991 20 multiple trauma patients with pelvic fractures and retroperitoneal bleeding from pelvic vessels underwent angiographic localization and embolization of massively bleeding arterial vessels. Nine patients survived (multiple trauma index grade III, Hanover polytrauma index), three patients with very severe injuries died immediately (multiple trauma index grade IV). After successful control of bleeding by embolization, three other patients died from severe brain injuries and five patients from septic multiorgan failure. The interval to definite localization and treatment of the bleeding source was three times shorter in the group of survivors, and the amount of transfusions needed was less by a factor of three. This underlines the importance of early angiography in multiple trauma patients with pelvic fractures and persisting hemorrhage. Embolization has proven to be effective in the treatment of such injuries. PMID- 1449941 TI - Epiphyseal chondroblastoma of bone. Long-term effects on skeletal growth and articular function in 15 cases treated surgically. AB - The authors describe the long-term sequelae of chondroblastoma in 15 patients with open growth plates, whose age at operation ranged from 8 to 15 years. At follow-up, the youngest patient was 21 and the oldest 48 years old. Upper limb length discrepancy ranging from 2 cm to 10 cm was present in the four patients who had a proximal humeral epiphyseal location; in three of them, the range of motion of the shoulder was also limited and X-rays showed marked irregularities of the humeral head. Lower limb length discrepancy ranging from 0.5 cm to 2 cm was found in five of the eight patients in whom the tumor affected lower limb epiphyses. One patient with proximal tibial epiphyseal involvement also had mild genu valgum. Radiographic osteoarthritis was present only in the trapeziometacarpal joint of a patient in whom the first metacarpal bone affected by the tumor was replaced by a free fibular graft. The abnormalities observed did not cause important functional loss in either the everyday or the working activities of any of our patients. PMID- 1449942 TI - Radiolunate and radioscapholunate arthrodesis. AB - Eleven patients underwent radiocarpal arthrodesis for a wrist disease other than rheumatoid arthritis. Operations included seven radiolunate fusions and four radioscapholunate fusions. The indication for surgery was posttraumatic changes secondary to radius fracture (five), Kienbock's disease (three), localized arthritis secondary to sepsis (two) and acute comminuted fracture of the distal radius (one). All patients had arthritis or post-traumatic changes limited to the articulation between the radius and carpus. Follow-up ranged from 24 months to 7 years, with an average of 41 months. Postoperatively, average range of motion of the wrist was 30.9 degrees of extension, 22.7 degrees of flexion, 10 degrees of radial deviation, and 19.3 degrees of ulnar deviation, and grip strength averaged 81.8% of that for the uninvolved hand. Pain relief was achieved in all patients, and they were able to return to their previous occupation. Bony union was achieved in all cases. Degenerative changes in the midcarpal joint were not seen. PMID- 1449943 TI - Immunoreactive neuropeptide nerves in ligamentous tissue in chronic shoulder pain. AB - Coracoacromial ligament and periligamentous fatty and loose connective tissue obtained during Neer's acromioplasty in patients with chronic painful rotator cuff tendinitis/impingement syndrome was studied for possible signs of inflammatory involvement and for the presence of neuropeptide-containing nerves, using routine histology and immunoperoxidase staining. No accumulations of inflammatory cells were found in the tissues studied. The dense ligamentous tissue proper was practically aneural, as was seen in staining for the generalized neuronal markers protein gene product 9.5 and synaptophysin. In contrast, the periligamentous fatty and loose connective tissue was innervated. Almost all nerves in such tissue contained C-flanking peptide of neuropeptide Y, whereas substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide-containing nerves were not found at all or were extremely rare. This suggests that the coracoacromial ligament is not a target of irritative inflammation. In the periligamentary sheath, nerves containing markers for the C type nociceptive pain fibers were practically absent and all local nerves were postganglionic sympathetic vaso-regulatory nerves. PMID- 1449944 TI - Open traumatic posterior dislocation of the hip. A case report. AB - A case of open traumatic posterior dislocation of the hip is presented. The femoral head and neck were completely out of the skin and there were accompanying fractures of the acetabular floor, the ischial ramus and the greater trochanter. To our knowledge, such a case has not been reported previously and this, together with its interesting mechanism, has led us to report the case. It was followed for 18 months and roentgenographic and 99mtechnetium sulphur colloid scanning studies showed avascular necrosis and osteoarthritis. PMID- 1449945 TI - Traumatic scapulothoracic dissociation. A case report. AB - A rare case of scapulothoracic dissociation which was not diagnosed initially is reported. Vascular injuries associated with this injury are potentially life threatening. The key to the diagnosis is accurate interpretation of the radiographs: the lateral dislocation of the acromion and lateral shift of the medial scapular border are evident on chest radiographs. Emergency subclavian arteriography is essential to assess the vascular status. A high index of suspicion has to be maintained so that this dangerous injury is not overlooked. PMID- 1449946 TI - Leg ulcer clinics: advanced nursing. AB - The author describes the development of a leg ulcer clinic, based on an electric model of care, which draws on her experience as a clinical nurse specialist. The philosophy of the clinic recognises that a 'legs specific' approach offers only short term solutions, and that a holistic method, which encourages patients to examine their own situation, is more appropriate. PMID- 1449947 TI - Clinical trials: comparing dressings. AB - This article describes results from one of the sites involved in a multi-centred comparative study designed to assess the performance of a collagen-alginate dressing used in the treatment of leg ulceration. The research methods used in the trial, as well as the results, will be of interest to practising nurses. Those involved in similar work are invited to submit articles to be considered for publication in future issues of this supplement. PMID- 1449948 TI - Formation of glycine conjugate and (-)-(R)-enantiomer from (+)-(S)-2 phenylpropionic acid suggesting the formation of the CoA thioester intermediate of (+)-(S)-enantiomer in dogs. AB - It has been proposed that the chiral inversion of the 2-arylpropionic acids is due to the stereospecific formation of the (-)-R-profenyl-CoA thioesters which are putative intermediates in the inversion. Accordingly, amino acid conjugation, for which the CoA thioesters are obligate intermediates, should be restricted to those optical forms which give rise to the (-)-R-profenyl-CoA, i.e., the racemates and the (-)-(R)-isomers. We have examined this problem in dogs with respect to 2-phenylpropionic acid(2-PPA). Regardless of the optical configuration of 2-phenylpropionic acid administered, the glycine conjugate was the major urinary metabolite and this was shown to be exclusively the (+)-(S)-enantiomer by chiral HPLC. Both (-)-(R)- and (+)-(S)-2-phenylpropionic acid were present in plasma after the administration of either antipode, and further evidence of the chiral inversion of both enantiomers was provided by the presence of some 25% of the opposite enantiomer in the free 2-phenylpropionic acid and its glucuronide excreted in urine after administration of (-)-(R)- and (+)-(S)-2-phenylpropionic acid. The (+)-(S)-enantiomer underwent chiral inversion to the (-)-(R)-antipode when incubated with dog hepatocytes. These data suggests that both enantiomers of 2-phenylpropionic acid are substrates for canine hepatic acyl CoA ligase(s) and thus undergo chiral inversion, but that the CoA thioester of only (+)-(S)-2 phenylpropionic acid is a substrate for the glycine N-acyl transferase. These studies are presently being extended to the structure and species specificity of the reverse inversion and amino acid conjugation of profen NSAIDs. PMID- 1449949 TI - Pulmonary inversion of 2-arylpropionic acids: influence of protein binding. AB - The possible contribution of pulmonary metabolism to the putative first-pass metabolism of 2-arylpropionic acid nonsteroidal antiinflammatory drugs has not been documented. Isolated perfused rabbit lungs, perfused with 4.5% bovine serum albumin or 5% dextran, were used to study the pulmonary elimination of (R)- and rac-ibuprofen, fenoprofen, and flurbiprofen. In the absence of protein binding, ibuprofen was metabolized via inversion and other pathways, whereas fenoprofen metabolism was essentially restricted to inversion of the (R)-enantiomer; fraction inverted (+/- SE) was 0.37 +/- 0.05 for (R)-ibuprofen and 0.85 +/- 0.03 for (R)-fenoprofen. In the presence of protein, neither ibuprofen nor fenoprofen was metabolized. Flurbiprofen did not undergo pulmonary elimination under any condition studied. This study illustrates that even though a tissue is capable of metabolism, particularly inversion of 2-arylpropionics, the quantitative importance of such elimination pathways may be minimal in the presence of the high degree of protein binding that is characteristic of these drugs. PMID- 1449950 TI - An improved synthesis of the enantiomers of BM-5 and their effects on the central in vivo release of acetylcholine. AB - Racemic N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)acetamide (BM-5), a putative postsynaptic agonist and presynaptic antagonist at muscarinic receptors, was resolved into the enantiomers by a new method suitable for large scale preparation. The method involves a chemoselective N-debenzylation as the key step. The enantiomers of BM-5 were obtained after six separate steps in 25% overall yield. The ability of the enantiomers to release acetylcholine was evaluated in vivo by use of brain dialysis. (R)-BM-5 was the more potent enantiomer in this assay. PMID- 1449951 TI - Absolute configuration and conformation of the pure opioid antagonist (+)-2,9 alpha-dimethyl-5-(m-hydroxyphenyl)morphan. AB - (+)-2,9 alpha-Dimethyl-5-(m-hydroxyphenyl)morphan is the only phenylmorphan analog whose affinity for opioid kappa-receptors is greater than its affinity for opioid mu-receptors. Pharmacologically, the compound is a pure opioid antagonist devoid of agonist activity in in vivo assays of antinociception. The absolute configuration of the compound has been determined to be (1R,5S,9R) from an X-ray crystallographic study of the chloride salt. Thus, the absolute configuration corresponds to that of the atypical opioid agonist (-)-phenylmorphan while the weak atypical agonist (-)-2,9 alpha-dimethyl-5-(m- hydroxyphenyl)morphan corresponds to the potent morphine-like (+)-phenylmorphan. The preferred orientations of the phenyl ring for the two stereoisomers were determined using the molecular mechanics program MM2-87 and found to vary from that of the two parent compounds. The atypical properties of the two 9 alpha-methyl analogs is consistent with an opioid ligand model which proposes that morphine-like properties require a particular range of phenyl orientations. There was good agreement between the structure obtained from X-ray crystallography and computed with the MM2-87 program. PMID- 1449952 TI - Application of time-domain fitting in the quantification of in vivo 1H spectroscopic imaging data sets. AB - Time-domain model function fitting techniques were applied to improve the reconstruction of metabolite maps from the data sets obtained from in vivo 1H spectroscopic imaging (SI) experiments. First, residual water-related signals were removed from the SI data sets by using SVD-based linear time-domain fitting based upon the HSVD (State Space) approach. Second, peak integrals of the metabolites of interest were obtained by quantifying the proton spin-echoes of the voxels by means of non-linear time-domain fitting based upon the maximum likelihood principle. Third, in order to save computational time, interpolation of the metabolite images (from size 32 x 32 to 128 x 128) was performed in the image-domain by applying one-dimensional cubic splines. It was found that the residual water signals can be almost completely removed from the SI data sets by applying the linear HSVD fitting method. Furthermore, it was found that voxel dependency of certain NMR parameters (e.g., variations of the spin-echo offset frequencies and/or phase factors) can be accounted for automatically by applying the nonlinear time-domain fitting technique. For that purpose it appeared to be essential to employ prior knowledge of the NMR spectral parameters. PMID- 1449953 TI - Quantitation of metabolites in human blood serum by proton magnetic resonance spectroscopy. A comparative study of the use of formate and TSP as concentration standards. AB - Formate has been evaluated as an alternative standard to quantitate human serum metabolites in 1H NMR spin-echo spectra. The comparison between added formate and 3-(trimethylsilyl) 3,3,3,3-tetradeutero-propionic acid (TSP) shows that, unlike TSP, formate does not interact with serum macromolecules. Transverse and longitudinal proton relaxation times have been measured on several serum metabolites, in the presence of ammonium chloride. With the exception of glucose, values of metabolite concentrations derived from Hahn spin-echo spectra recorded on serum containing 15.4 mM exogenous formate as a standard, are in excellent agreement with the results of biochemical and chromatographic assays, after correction for differential relaxation effects. This approach can be readily used for quantitation of metabolites from blood serum (and eventually other physiological fluids) in normal and in pathological situations not involving disorders of endogenous formate metabolism. PMID- 1449954 TI - Phosphorus metabolite characterization of human prostatic adenocarcinoma in a nude mouse model by 31P magnetic resonance spectroscopy and high pressure liquid chromatography. AB - A series of experiments were conducted to identify and quantify the phosphorus metabolites of DU 145 xenografts (a human prostatic adenocarcinoma cell line grown in nude mice) using 31P MRS and HPLC. The 31P spectral characteristics of DU 145 xenografts were compared to perfused DU 145 cells and to in situ human prostatic adenocarcinomas. These studies demonstrated that both DU 145 xenografts and perfused DU 145 cells exhibited reduced levels of phosphocreatine relative to spectra of in situ human prostatic adenocarcinomas. Elevated levels of phosphomonesters (PMEs) were observed in 31P spectra of both DU 145 xenografts and in situ human prostatic adenocarcinomas. The major components of the PME resonance of DU 145 xenografts were identified as phosphocholine and phosphoethanolamine. High levels of diphosphodiesters (DPDEs) were consistently observed for both DU 145 xenografts and perfused DU 145 cells, but were absent in 31P spectra in in situ primary human adenocarcinomas. In agreement with spectroscopic results, high pressure liquid chromatographic analyses of human tissue removed at surgery contained insignificant amounts of DPDEs while DU 145 xenografts had high levels of DPDEs consisting mainly of uridine-5'-diphospho-N acetylgalactosamine (22.4 nmol/mg protein) and uridine-5'-diphospho-N acetylglucosamine (7.4 nmol/mg protein). PMID- 1449955 TI - Direct absolute quantification of metabolites in the human brain with in vivo localized proton spectroscopy. AB - The absolute concentrations of the three major brain metabolites observable by in vivo proton spectroscopy--N-acetylaspartate(NAA), creatine and phosphocreatine (Cr and PCr) and choline (Cho)--have been measured at four standardized localizations in 34 healthy volunteers by in vivo localized proton spectroscopy using an external reference sample. The results show that the concentration of Cr and PCr as observed by in vivo MRS (5-6 mmol/L) is lower than that measured by other methods. The results are concordant with the hypothesis, that the Cr and PCr resonance as observed by proton spectroscopy is due mainly to PCr, whereas Cr remains invisible by being attached to a larger molecule. It is also demonstrated, that Cr and PCr is higher in the cerebellum than in the cerebrum, whereas NAA remains constant within the margin of error (8-9 mmol/L). PMID- 1449956 TI - Experimental characterization of the ISIS technique for volume selected NMR spectroscopy. AB - As clinical applications of MRS grow in number and complexity, there is a need for standardized methods for characterizing the performance of volume selection techniques. The results are presented of a thorough evaluation of a particular implementation of ISIS performed using a procedure which forms the basis of the method adopted by the European Community Concerted Action on MRS and MRI. We have found that ISIS localization is optimal when the volume of interest is slightly smaller than the region we wish to study. Contamination with extraneous signal has little T1 dependence so long as TR greater than T1 and the detection pulse angle is 90 degrees. However, a poorly optimized detection pulse results in T1 weighted contamination unless TR greater than 3T1. In the clinical context, this corresponds to a different degree of contamination for each peak in the spectrum. Adiabatic detection pulses were used in an attempt to overcome this problem without resorting to unacceptable TR values, but these were found to function less well than properly optimized rectangular pulses, even if the power was increased above the level determined by the system for B1 insensitivity. These detailed results pertain only to our system, but illustrate the importance of performing similar measurements as part of clinical spectroscopy programmes at other centres. PMID- 1449957 TI - Motional degradation of metabolite signal strengths when using STEAM: a correction method. PMID- 1449958 TI - The clinical use of magnetic resonance spectroscopy. PMID- 1449959 TI - The biochemistry of living tissues: examination by MRS. AB - MRS defines the molecular state of water, the chemical environment of cells and tissues and the qualitative and quantitative state of intermediary metabolism. Because cancer has disordered physiology, obvious differences in MR spectra can be observed. However, the detailed understanding of the biochemistry of cancer will also emerge from careful, quantitative multinuclear MR. The intermediary metabolism of ATP, the Krebs cycle, creatine, cholines and lipids, is discussed. Finally, the biochemical challenge posed by oncogenes may be amenable to MR analyses. PMID- 1449960 TI - Physiological properties of malignant tumours. AB - It is generally accepted that tumour microcirculation, blood flow, oxygen and nutrient supply, tissue pH distribution, and the bioenergetic status--factors which are usually closely linked and which define the so-called metabolic microenvironment--can markedly influence the therapeutic response of malignant tumours to conventional irradiation, chemotherapy, other non-surgical treatment modalities, and the cell proliferation activity within the tumours. Currently available information on the parameters defining the metabolic micromilieu in human tumours is presented in this paper. According to these data, significant variations in these relevant factors are likely to occur between different locations within a tumour, and between tumours of the same grading and clinical staging. Therefore, evaluation of the metabolic microenvironment in individual tumours before therapy and a corresponding 'fine-tuning' of treatment protocols for individual patients may result in an improved tumour response to treatment. PMID- 1449961 TI - Phospholipid metabolites as indicators of cancer cell function. AB - NMR methods are being applied to study phospholipid metabolism of cancer cells by monitoring the resonances which appear in the 31P spectrum. This review, aside from considering the applicability of NMR to this specific pathway, raises the question of whether the phospholipid metabolite peaks observed by MR are indicators of cancer cell function or tumor response to treatment. After assessing the results from many investigations, it is concluded that there is no clear correlation and that a combination of techniques, including in vitro and extract studies, will be necessary for a more comprehensive evaluation of the in vivo data. PMID- 1449962 TI - The choice of experimental models in cancer research: the key to ultimate success or failure? AB - The technologies available for assessing the size and physiological status of malignant tumours are becoming more and more sophisticated. Some of these detect phenotypic biochemical alterations resulting from the genetic changes associated with malignant transformation. Many, however, monitor the abnormal relationship between the tumour mass and the host, detecting pathophysiological changes which result from the host/tumour interaction. The most important of these involve the microregional heterogeneities of nutrients resulting from diffusion patterns around abnormal, newly-formed vascular networks, or inflammatory or immune responses of the host to the tumour. In order to validate new technologies for introduction to clinical medicine they are usually extensively tested in experimental models for cancer. The relevance of these models (whether in vitro cell cultures or experimental tumours) must be considered carefully at the outset, with the factors that influence the parameter being measured, e.g., oxygen or energy status, being given special attention. The genetic similarity of tumour and host, the site of tumour growth, the size of the tumour, the burden it imposes and the immunocompetence of the host are all important features of the experimental model. Inappropriate models may give totally misleading information which cannot be extrapolated to human cancers. PMID- 1449963 TI - Practical applications of chemical shift imaging. AB - Methods of spectral localization are briefly reviewed and divided into two classes: those using phase encoding and those using frequency selective RF pulses in a constant gradient. A potentially troubling artifact in the latter case is the spatial misregistration of different compounds which causes serious errors in 31P spectra from smaller regions. Chemical shift imaging (CSI) is presented as a typical example of phase encoding techniques. An analytical expression for the relationship of the signal observed to the true signal (the point spread function) is derived. Examples of CSI in one, two, and three dimensions are used to illustrate the principles of this type of localization. PMID- 1449964 TI - Practicalities of localization in animal and human tumours. AB - Factors affecting the selection and application of localization methods for measuring tumours by NMR spectroscopy are considered, with particular regard to the S/N ratio and to contaminating signal from outside the volume of interest. Methods of assessing the performance of localization techniques are considered, and their importance for quantitative measurements and comparative studies is discussed. PMID- 1449965 TI - Bioluminescence and fluoroscopic imaging of tissue pH and metabolites in experimental brain tumors of cat. AB - The regional distribution of ATP, glucose, lactate and tissue pH was studied by bioluminescence and fluoroscopic imaging of intact cryostat sections of implantation tumors of cat. In tumors, marked heterogeneity of metabolites and pH was present: in solid parts ATP was similar to normal brain but glucose tended to decrease with an increase in lactate and pH to above normal; in necrobiotic regions ATP declined and pH became acidic. In peritumoral edema, ATP was consistently decreased whereas glucose, lactate and pH increased above normal. Correlation of ATP with water revealed an inverse relationship both in tumor and peritumoral edema but correlation of water with pH was direct in edema and inverse in tumors. The associations and dissociations of lactate, ATP and pH are interpreted in terms of aerobic and anaerobic glycolysis, as well as in respect to the extracellular localization of tumor edema. The findings are of relevance for the interpretation of volume selective NMR spectra and stress the importance of precise volume localization for differentiating between edema and tumor mediated metabolic alterations. PMID- 1449966 TI - Positron emission tomography for tumour assessment. AB - As positron emission tomography (PET) is outside of the main theme of this conference, it is necessary to outline what it offers as a method for assessing tissue function in vivo. This is followed by illustrations of how PET has and is being used to study the physiology and biochemistry of tumours and pharmacokinetics and pharmacology of anticancer agents. Strategies are offered as to how PET may be used for the development of new chemotherapeutic agents. PMID- 1449967 TI - Non-invasive MRS in new anticancer drug development. AB - In the rational development of anticancer drugs it is important to employ all the available pharmacological information. Early clinical trials provide an opportunity for hypothesis testing. MRS techniques have the potential to provide valuable data on the preclinical and clinical pharmacokinetics and pharmacodynamics of drugs non-invasively. Here we illustrate advantages and pitfalls of MRS using studies of two fluorine-containing cancer drugs: a beta,beta-difluoro analogue of the alkylating agent chlorambucil and a fluorinated derivative of the nitroimidazole misonidazole, Ro 07-0741. Limitations include signal quenching via protein binding and inadequate sensitivity for more potent drugs like beta,beta-difluorochlorambucil; but fluoromisonidazole was shown to accumulate in tumours and shows promise as a chemical probe for tumour hypoxia, detectable by 19F MRS. PMID- 1449968 TI - In vivo and ex vivo magnetic resonance spectroscopy as applied to pharmacokinetic studies with anticancer agents: a review. AB - The potential role of MRS in studying the pharmacokinetics of anticancer drugs is reviewed. In vivo and ex vivo MRS has been used extensively in studies with fluoropyrimidines. Results from preclinical models have demonstrated that biochemical modulation of 5-fluorouracil metabolism can be demonstrated by MRS. The more general potential of MRS is illustrated by studies with the antifolate CB3988 (C2-desamino-C2-methyl-N10-propargyl-2'-trifluoromethyl-5,8-dideazafolic acid). Studies in mice and rats have shown that hepatobiliary clearance and renal elimination can be measured non-invasively by MRS. Comparison of half-lives derived from MRS and high performance liquid chromatography data gave reasonable agreement. In addition, MRI was used to localize drug-derived material within the abdominal cavity. The application of ex vivo MRS is illustrated by studies on the urinary excretion of platinum complexes. 1H-MRS has been used to demonstrate the presence of the cyclobutanedicarboxylate leaving group, both free and platinum bound, in the urine of patients treated with carboplatin. With iproplatin 195Pt NMR has been used to demonstrate in vivo reduction of this Pt(IV) complex to Pt(II) complexes. Finally, the application of MRS to the study of the molecular pharmacology of alkylating agents (a nitrogen mustard and N-methyl-N-nitrosourea) is discussed. PMID- 1449969 TI - The contribution made by cell death and oxygenation to 31P MRS observations of tumour energy metabolism. AB - This review discusses the relationship between tumour oxygenation status, tumour cell death and the 31P MRS parameters associated with cellular energy metabolism (phosphocreatine, nucleoside triphosphates and Pi). The presence of cells dying by apoptosis, and during mitosis would be unlikely to affect the 31P spectrum directly since they represent only a small fraction of tumour cells and remain energized until phagocytosed. Histologically necrotic cells also probably contribute nothing to the 31P spectrum. Instead, the spectrum appears to reflect the degree of hypoxia of the remaining viable cells, and the metabolic alterations required to sustain ATP synthesis as the oxygen supply diminishes. The biochemical theory developed to account for the 31P spectra of acutely hypoxic tissues does not apply to chronically hypoxic tumours. The concentrations of free ADP and Pi have major roles in the control of oxidative phosphorylation and glycolysis, as in normal tissues, but the precise relationships are still obscure. Cell-killing following therapy may indirectly affect 31P MRS parameters via changes in oxygen concentration brought about by an improvement in tumour blood flow and alterations in oxygen consumption rates and diffusion distances. PMID- 1449970 TI - Measurement of tumor blood flow by deuterium NMR and the effects of modifiers. AB - Tumor metabolism is directly coupled to tumor blood flow (TBF) and both metabolism and blood flow may be determinants of tumor response to treatment. Since NMR has been used extensively to monitor tumor metabolism noninvasively, development of NMR-based methods for TBF measurement was motivated by the desire to examine the roles tumor metabolism and blood flow may play as determinants of therapeutic response. The concept of using deuterated water as an NMR-detectable, flow-limited tracer for the measurement of tissue blood flow (or capillary perfusion) was introduced in 1987 by Ackerman and coworkers (Proc. Natl., Acad. Sci., USA 84, 4099-4102 (1987)). Since that time, methods have been devised using both spectroscopic and imaging detection for TBF measurement based on either clearance or uptake of deuterated water. In general, the clearance methods are more straightforward to implement, while the uptake methods are less invasive to the tumor. When used with appropriate caution, both approaches yield reliable results. To date, these methods have been applied in a relatively limited number of animal tumors. However, their use is increasing and some of these methods ultimately should be applicable in human tumors. PMID- 1449971 TI - Clinical experimentation in magnetic resonance spectroscopy: a perspective from the National Cancer Institute. AB - This paper describes the National Cancer Institute activities in clinical MRS, including a recent international conference organized by the Diagnostic Imaging Research Branch, a research agenda developed by the conference faculty members of one of the research programs proposed by the author. PMID- 1449972 TI - A plea for support of referenda to increase excise taxes on tobacco. PMID- 1449973 TI - Erythropoietin for anemia of cancer: higher hematocrits, fewer transfusions. PMID- 1449975 TI - A special series: management of medical emergencies in cancer patients. PMID- 1449974 TI - The use of the polymerase chain reaction in clinical oncology. AB - The polymerase chain reaction (PCR) is an extraordinary tool for studying cancer. It is both more sensitive and more rapid than any other detection method, and can be performed without special expertise. It is ideal for the detection of minimal residual disease, particularly in lymphoid malignancies, but also for any cancer with a genetic abnormality that is defined at the molecular level. Other uses, such as diagnosis of cancer based on detection of translocations or point mutations, have an intriguing potential, but remain investigational. At this point, few clinicians would be willing to base a diagnosis, let alone a treatment plan, on a diagnosis based on PCR findings without confirming histology. PMID- 1449977 TI - Clinical trials referral resource. Rhabdomyosarcoma. PMID- 1449976 TI - Acute renal failure in cancer patients. AB - Compromise of kidney function in patients with serious medical illnesses, including cancer, is a serious and potentially fatal complication. In cancer patients, the types of renal injury that may occur are more varied than in patients with other underlying illnesses, and definition of the etiology of the decline in renal function may have important therapeutic and prognostic implications. This review article discusses the clinical manifestations and the diagnostic workup of insults to the kidney in patients with cancer. Therapy (excluding dialysis) for each type of renal insufficiency is briefly reviewed. PMID- 1449978 TI - Recognizing the oral manifestations of AIDS. AB - The first sign of HIV infection may be an unusual or rapidly progressive condition of the oral cavity, including malignancies such as Kaposi's sarcoma. Early diagnosis of these oral conditions can lead to early diagnosis of HIV infection and subsequent treatment with antiretroviral agents that may improve the prognosis. This illustrated review outlines the presenting signs and symptoms of the most common oral manifestations of the AIDS virus, including hairy leukoplakia, candidiasis, Kaposi's sarcoma, periodontal disease, salivary gland disease, necrotizing stomatitis, and infection with herpes and human papillomavirus. PMID- 1449979 TI - New oral agent for PCP is effective, well tolerated. PMID- 1449980 TI - Lymphoma, hairy-cell leukemia respond to new agents. PMID- 1449981 TI - Genetic etiology of lung cancer. AB - Although the clinical management of lung cancer has not changed substantially over the past decade, this same time period has witnessed exciting new developments concerning the origins of this disease. These findings support the hypothesis that lung cancer, as well as other common adult tumors, arise as a result of somatic mutations to a specific group of cellular genes referred to as oncogenes and tumor suppressor genes. New strategies for the prevention and treatment of lung cancer will emerge as we identify the mechanisms that control mutation rates for these target genes and gain a better understanding of the role these genes play in coordinating normal cell growth and differentiation. PMID- 1449982 TI - Malaria. Ministerial Conference on Malaria, Amsterdam. PMID- 1449983 TI - Global health situation. II. Health and environment: urbanization, literacy, water supply and sanitation. PMID- 1449984 TI - Expanded programme on immunization. Program review. PMID- 1449985 TI - Trends in sex ratios of cancer mortality in Europe. 1950-1989. PMID- 1449986 TI - Expanded programme on immunization (EPI). Safety of high titre measles vaccines. AB - Unexpected results suggesting decreased survival when compared with standard titre vaccine administered at 9 months of age have been found in some field studies evaluating the performance of high titre measles vaccine. Analytical difficulties have arisen because the studies were not specifically designed to measure survival. Nonetheless, careful analysis of the results from all of the high titre vaccine trials showed decreased survival of high titre vaccine recipients, in areas with high background mortality rates, compared with recipients of standard measles vaccines at 9 months. No systematic biases could be found in the studies to explain these differences. Statistical analysis of these data suggested that the findings were unlikely to be attributable to chance alone. The panel recommended that high titre measles vaccine derived from the original Edmonston measles vaccine isolate should no longer be recommended for use in immunization programmes. Further post-licensure field studies of new measles vaccines should take into account the results of these studies. Additional detailed epidemiological studies in populations that have received high titre vaccines and their controls were encouraged. PMID- 1449987 TI - Rabies. Two cases of imported rabies in France. PMID- 1449988 TI - Need for consistency in AIDS education. PMID- 1449989 TI - School nursing. The first hundred years. PMID- 1449991 TI - School nursing. The next hundred years. PMID- 1449990 TI - School nursing. 'Pearl is like a mum'. PMID- 1449992 TI - Accident & emergency: care and transfer of the burns patient. AB - A patient with major burns requires intervention from highly skilled nursing and medical teams on arrival at the accident and emergency department, and those staff without proper training can lack confidence in dealing with such a situation. The author offers guidance and advice for nurses in A&E on initial treatment of the burns patient, and discusses the preparation necessary before transferring the victim to another area, as well as the transfer itself. PMID- 1449993 TI - Should nurses wear name badges? AB - In the third and final part of the series of articles on the implications of the 'named nurse' initiative, Stephen Wright looks at the issue of name badges and whether wearing them enhances nurse/patient relationships or poses personal risks to staff. Much of the current information related to the debate is anecdotal, suggesting that formal research on the issues would be useful. PMID- 1449995 TI - Nursing research: exploring the options. PMID- 1449994 TI - Wound care: conflict or collaboration? PMID- 1449996 TI - Tackling staff absenteeism. PMID- 1449997 TI - Mentorship for everyone. PMID- 1449998 TI - The standard guide to ... writing your CV. PMID- 1450000 TI - Theatre nursing. Knowledge to care. PMID- 1449999 TI - Theatre nursing. Making order out of chaos. PMID- 1450001 TI - Theatre nursing. European developments in theatre nursing. PMID- 1450002 TI - Theatre nursing. An alternative to swab racks. PMID- 1450003 TI - Women who prostitute are practising safer sex. PMID- 1450004 TI - Xerostomia and treatment with ddI. PMID- 1450005 TI - Skill mix and the effectiveness of nursing care. PMID- 1450006 TI - Growing straight. PMID- 1450007 TI - Learning disabilities. Using hydrotherapy: maximising benefits. AB - People with a learning disability are increasingly using hydrotherapy for exercise, socialising, and the release of tension and energy. For those with a physical disability, it offers an opportunity for independent activity from which they may be precluded outside the hydrotherapy pool. The author discusses guidelines for staff involved in hydrotherapy sessions before examining in detail the benefits this form of treatment has to offer. PMID- 1450008 TI - Uncommon disorders. Helping lumbosacral arachnoiditis patients. PMID- 1450009 TI - Time management in a day surgery unit. PMID- 1450010 TI - Development of an in vitro bladder model. AB - The first of the three articles in this series (1) expounded the case for a broader approach to research design in nursing. In particular, the experimental approach and the use of laboratory studies were highlighted as areas that nurses have tended to neglect. This second article explores the development of an in vitro bladder model for use in experiments examining infections in catheterised patients. PMID- 1450011 TI - The Clay column. PMID- 1450012 TI - Legal matters: the beverage report. PMID- 1450013 TI - Soapbox: bedevilled advocates. PMID- 1450014 TI - Cardiology update. Health education and heart disease. PMID- 1450015 TI - Cardiology update. VasoSeal. PMID- 1450017 TI - Cardiology update. Computers in cardiac nursing. PMID- 1450016 TI - Cardiology update. The sound revolution. PMID- 1450018 TI - Heart disease: reducing the risks (continuing nursing education). PMID- 1450020 TI - Pay and conditions: the state of the nursing nation. PMID- 1450019 TI - Pressure sores: a case to answer (continuing nursing education). PMID- 1450021 TI - Community care: can't pay, won't pay? PMID- 1450022 TI - HIV/AIDS: beyond the fringe. PMID- 1450023 TI - Health service management: changing the face of London's health care. PMID- 1450024 TI - Responding to need. PMID- 1450025 TI - The bladder model: clinical implications. AB - The first two articles in this series (1, 2) discussed the importance of the experimental approach within nursing research, and described the development of a bladder model which could be used to investigate errors in practice. The final article will document the use of this model in examining the design features of four urinary drainage bags and in investigating the effect of a potential error in practice. PMID- 1450026 TI - Pressure sores and intra-operative risk. AB - The enormous cost of pressure sore care is well documented (1, 2), but a review of the available literature shows few studies on the genesis of intra-operative pressure sores exist and the contribution of operating room exposure as an aetiological factor is largely undefined. This article provides a brief overview of the aetiology of pressure sores, details interface pressures reported on operating tables, and critically reviews the literature suggesting a link between events during the intra-operative period and post-operative pressure sore formation. PMID- 1450027 TI - Relieving stress in a neurosurgical unit. PMID- 1450028 TI - The Sister Susie column. New nursing laid open. PMID- 1450029 TI - Tradimus. An end to the Project. PMID- 1450030 TI - Tradimus. Project 2000: second rate for graduates? PMID- 1450031 TI - Tradimus. A day in the life: confessions of a mature student. PMID- 1450032 TI - Tradimus. Mental health: on the patients' side. PMID- 1450033 TI - Tradimus. Lifting techniques: put your back out of danger. PMID- 1450034 TI - Tradimus. Unworkable paradox. PMID- 1450035 TI - AIDS and cancer: let's begin thinking globally. PMID- 1450036 TI - To fight AIDS, the Swiss Government ready to provide heroin. PMID- 1450037 TI - A therapeutic withdrawal can make a strategic advance. PMID- 1450038 TI - Antiosteolytic agents in the management of hypercalcemia. PMID- 1450039 TI - Infusional anthracyclines: is slower better? If so, why? PMID- 1450040 TI - The epidemiology of acquired immunodeficiency syndrome and associated tumours in Europe. AB - By the end of September 1991, more than 60,000 cases of acquired immunodeficiency syndrome (AIDS) had been reported to the World Health Organization (WHO) by 31 countries in the WHO European region. Most of the cases (58,280/60,485-96%) were recorded in western Europe, chiefly in five countries: France (16,552 cases), Italy (10,584), Spain (10,101), Germany (6,968) and the United Kingdom (5,065). From the first reports in 1981 of European cases of AIDS until 1987, AIDS spread faster in the northern and central areas than elsewhere in the European region. Since then, the spread of the epidemic has been remarkably more rapid in southern Europe, while in eastern Europe AIDS is still in an early phase. More than 70% of the cases among homosexual or bisexual men were from the northern part of Europe, while the cases among intravenous drug users (IVDUs) were concentrated in the southern European countries, principally Italy and Spain. Over time, an increasing proportion of cases was recorded among IVDUs and in heterosexuals. More than 10,000 patients in Europe were diagnosed as having Kaposi's sarcoma (KS) (14% of all AIDS cases) or non-Hodgkin's lymphoma (NHL) (3%) as the presenting clinical manifestation of AIDS. The possibility of predicting the evolution of the epidemic in Europe depends heavily on the development of unbiased monitoring systems for HIV infection in the general population (i.e. anonymous unlinked testing). PMID- 1450041 TI - Allergic reactions to cytotoxic drugs--an update. PMID- 1450042 TI - Response after withdrawal of tamoxifen and progestogens in advanced breast cancer. AB - Tumor response after withdrawal of endocrine therapy for advanced breast cancer with estrogens and androgens is well described. There have been few reports of withdrawal responses (WRs) after cessation of treatment with the newer antiestrogens and progestogens. We assessed WR in women after cessation of adjuvant therapy at first relapse, and after progression on first, second or third line endocrine therapy for advanced disease. One of seven patients (14%) responded after cessation of tamoxifen adjuvant therapy at relapse. Sixty-five of 72 patients were evaluable for WR after cessation of tamoxifen as first line therapy for advanced disease. There were five partial responses (8%) and 14 (22%) 'no change' with a median duration of WR of 10 months (range 3-40 months). WR were seen mainly in soft tissue disease but there were two responses in lung and two in bone. Four of 21 (19%) patients had a WR after cessation of norethisterone acetate (3) and tamoxifen (1), all used as second line therapy. WR are therefore demonstrable after cessation of tamoxifen and norethisterone acetate with durations of response similar to those found with additive therapy. Assessment of WR may represent a way of prolonging the overall response duration in patients with relatively indolent metastatic breast cancer, particularly in soft tissues. PMID- 1450043 TI - Plicamycin and pamidronate in symptomatic tumor-related hypercalcemia: a prospective randomized crossover trial. AB - We have conducted a randomized crossover comparative trial of a single-dose course of disodium (3-amino-1-hydroxypropylidene) bisphosphonate pentahydrate (pamidronate) and plicamycin in 48 patients with a first occurrence of tumor related hypercalcemia. All patients had hypercalcaemia-associated symptoms and serum-calcium levels (corrected for total protein) greater than or equal to 2.80 mmol/l. Pamidronate and plicamycin were given concurrently with rehydration immediately after diagnosis of hypercalcaemia was made. Both agents lowered serum calcium levels significantly within 1 week, with 88% of the evaluable patients in the pamidronate group and 45% of those in the plicamycin group achieving normocalcemia (p less than 0.01). In the patients who received pamidronate, the duration of normocalcemia was longer (p less than 0.05) and there was a significant decrease in serum creatinine (p less than 0.05). Vomiting occurred in 8 of 22 evaluable patients (36%) who received plicamycin, but in none of 25 evaluable patients who received pamidronate (P less than 0.01). Phlebitis occurred at the infusion site in more of the pamidronate-treated patients (P less than 0.05). Hypocalcemia, which occurred in 8 of 25 evaluable patients (32%) in the pamidronate group and in 1 of 22 of those (5%) in the plicamycin group, was either clinically asymptomatic or mild, except in one pamidronate-treated patient. Overall, pamidronate was found to be more effective and better tolerated than plicamycin, thereby confirming results of previous studies that showed pamidronate to be an effective, simple, and safe agent for the relief of the morbidity associated with tumor-related hypercalcemia. PMID- 1450044 TI - The role of age at menarche and at menopause on breast cancer risk: combined evidence from four case-control studies. AB - The role of age at menarche and at menopause on breast cancer risk was reassessed in a combined analysis of four Italian case-control studies including a total of 6,075 cases and 5,492 controls. The risk of breast cancer was lower in women whose menarche occurred at age 15 or over, but there was no evidence for the risk to increase with decreasing age at menarche below age 15. Compared with women with earlier menarche, the relative risk (RR) was 0.9 (95% confidence interval, CI 0.7-1.0) for those with menarche at age 15, 0.8 (95% CI 0.6-0.9) for menarche at 16, and 0.7 (95% CI 0.5-0.8) for menarche at age 17 or over. There was no significant interaction between age at menarche and study centre or age at diagnosis, parity and age at first birth. In relation to age at menopause, compared with women whose menopause occurred at age 40 or less, the relative risk was 1.1 (95% CI 0.8-1.3) between 40 and 44, 1.2 (95% CI 0.9-1.4) between 45 and 49, 1.4 (95% CI 1.2-1.8) between 50 and 53, and 1.4 (95% CI 1.1-1.8) above 53. The risk estimates were comparable in various studies, and the trend in risk with age at menopause was statistically significant. The risk estimates tended to be somewhat higher at peri-menopausal age (45 to 54 years), but no consistent pattern was evident across subsequent strata of age, and the interaction with age was not significant. Likewise, no consistent interaction was observed with parity, age at first birth or body mass index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450045 TI - Subsets of tumors responsive to cisplatin or carboplatin combinations in patients with carcinoma of unknown primary site. A Hellenic Cooperative Oncology Group Study. AB - In this retrospective analysis 48 patients with metastatic undifferentiated carcinoma, adenocarcinoma and epidermoid carcinoma of unknown origin were studied. The purpose of this analysis was to evaluate both the response rate and the toxicity of combination chemotherapy containing cisplatin or carboplatin, and to attempt to identify certain clinical subsets of patients sensitive to these drugs. Four patients were not evaluable and 13 (29.5%), eight of the 34 treated with regimens containing cisplatin and 5/14 with carboplatin-based chemotherapy, responded to treatment. Six of the 23 with undifferentiated tumours, 4/17 with adenocarcinomas and 3/8 with epidermoid cancers responded to chemotherapy. Four of 6 women with adenocarcinoma of the peritoneal cavity, 5/11 with undifferentiated carcinomas with midline distribution and 3/5 with epidermoid carcinomas of the cervical nodes responded. Seven patients achieved complete and six partial remissions. The mean duration of response was nine months; a number of patients enjoyed prolonged and/or durable remissions. Toxicity was tolerable. We conclude that: (a) both cisplatin and carboplatin are active agents in this syndrome with one-third of the evaluable patients responding, and (b) there may be chemosensitive subgroups, such as patients with peritoneal adenocarcinomatosis, undifferentiated carcinoma with midline distribution and metastatic epidermoid carcinoma of the neck nodes. The effectiveness of carboplatin in these patients and the responsiveness of metastatic epidermoid carcinoma of unknown origin have not been adequately dealt with in the literature. PMID- 1450046 TI - Treatment with alpha-interferon versus alpha-interferon in combination with streptozocin and doxorubicin in patients with malignant carcinoid tumors: a randomized trial. AB - An open randomized trial was performed to compare the effect of recombinant interferon-alpha 2a (rIFN-alpha 2a) (group A, n = 12) versus rIFN-alpha 2a in combination with chemotherapy (group B, n = 11) in patients with malignant carcinoid tumors. Both groups received rIFN-alpha 2a at a dose of 3 MU/m2 s.c. three times weekly during the first 6 months. IFN was discontinued every third week in group B, followed by an i.v. injection of 2 g streptozocin and 40 mg/m2 doxorubicin. After 6 months group A showed one complete biochemical response (CR), 9 patients with stable disease (SD) and 2 who progressed (PD). Two patients had a partial reduction (PR) of tumor size, 9 showed SD and one PD. All patients in group B demonstrated SD. Chemotherapy was withdrawn after 6 months and all patients continued with rIFN-alpha 2a at an increased dose of 3 MU/m2 five days/week for a further 6 months. After 12 months 6 patients showed PR, 12 SD and one PD biochemically. Tumor size showed SD in 18 patients and PD in one. One patient died from cardiomyopathy, probably induced by doxorubicin. Antibodies against rIFN-alpha 2a developed in 41% of the patients. In conclusion, we detected no difference in response rates between the two treatment groups. Adverse reactions from the combination were considerable. The frequent development of IFN antibodies might have interfered with the therapeutic results. PMID- 1450047 TI - Pharmacokinetics and metabolism of epirubicin administered as i.v. bolus and 48-h infusion in patients with advanced soft-tissue sarcoma. AB - We have studied the pharmacokinetics of epirubicin after its administration in sarcoma patients either as an i.v. bolus or as a 48-h infusion (5 courses each; 9 patients in total). Bolus injection was followed by a three exponential decay in plasma, with half-lives of 2.43 min, 1.95 h and 21.7 h; 48-h infusions were characterized by the very rapid establishment of a plasma plateau concentration followed by a biexponential decay after stopping the infusion. Pharmacokinetic parameters such as total plasma clearance, total volume of distribution, mean residence time and elimination half-life were similar, irrespective of the duration of the administration. In contrast, the relative amounts of the metabolites of epirubicin were reduced when the drug was administered over 48 h; in particular, the plasma levels of epirubicin glucuronide never exceeded those of epirubicin, which always occur after bolus injection. This may result from a lower availability of epirubicin for metabolism. These results now require validation in a larger group of patients using a cross-over design. PMID- 1450048 TI - Bi-weekly 2-day schedule of high-dose folinic acid, 5-fluorouracil bolus and infusion in pretreated advanced epithelial ovarian cancer: a phase II study. AB - Twenty patients with documented progression after two or three cisplatin-based regimens for advanced epithelial ovarian carcinoma were treated with high-dose folinic acid (200 mg/m2), 5-fluorouracil bolus (400 mg/m2) and continuous infusion (600 mg/m2) for two consecutive days every two weeks. One clinically complete and two partial responses were observed in 16 evaluable patients, with 5 remaining stable. Median survival was 9 months. Toxicity was mild. This combination achieved a 19% (95% confidence interval 4%-46%) response rate in heavily pretreated cisplatin-resistant patients. PMID- 1450049 TI - Multicenter phase II trial of brequinar sodium in patients with advanced melanoma. AB - Seventeen patients with advanced melanoma and no prior exposure to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously. In 14 patients evaluable for efficacy, there were no objective responses. The toxicity was moderate. We conclude that, at this dose and schedule, brequinar has no activity in advanced melanoma. PMID- 1450050 TI - Treatment of resistant tumor-induced hypercalcemia with escalating doses of pamidronate (APD). PMID- 1450051 TI - Interferon alpha-2-beta enhances immunoscintigraphic localization of monoclonal antibody in malignant melanoma. PMID- 1450052 TI - Mechanisms of hypercalcemia in lymphomas. PMID- 1450053 TI - Researchers home in on the elusive stem cell. PMID- 1450054 TI - 'Staging' systems for aggressive non-Hodgkin's lymphoma. PMID- 1450055 TI - Serotonin antagonist antiemetics: progress and concerns. PMID- 1450056 TI - The enigma of ifosfamide encephalopathy. PMID- 1450057 TI - Meta-analysis: the fashion of summing-up evidence. Part II: Interpretations and uses. AB - In this commentary, we use evidence produced by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) ten-year update of a meta-analysis of trials of adjuvant therapies for early breast cancer which started prior to 1985 to illustrate aspects of interpretations and uses of meta-analysis results. The following issues are discussed: i) The meta-analysis provides an average summary for the effect of a treatment. Greater statistical power is obtained by increasing the number of events contributing to the analysis. However, summing up the results of various trials necessitates the loss of individual information concerning the magnitude of treatment effects which depend on tumor- and patient related factors. Subgroup analyses within the meta-analysis process allow some recovery of such features; ii) The absolute benefit obtained from an effective treatment depends not only on the relative benefit of the treatment but also on the prognosis of the individual patients; iii) The results are more immediately applicable if less reliance is placed on the arithmetic construct inherent in the overview, using instead unconfounded information about the value of treatments actually administered. This avoids the need to extrapolate the effect for one component of the therapy by assuming a lack of interaction with its other components; iv) Although indirect comparisons between different meta-analyses are regularly made to pick the "winner" from among tested treatment modalities, it is unlikely that the optimal therapeutic regimen can be defined via such indirect comparisons, though such comparisons may raise interesting, testable hypotheses. PMID- 1450058 TI - Emerging from a crisis in anticancer drug discovery? Screening versus design: confessions of an optimistic fence-sitter. PMID- 1450059 TI - Current results with rhizoxin: the evaluation of a clinical and a basic scientist. PMID- 1450060 TI - A proposal for a simple staging system for intermediate grade lymphoma and immunoblastic lymphoma based on the 'tumor score'. AB - A new staging system for intermediate grade lymphomas and immunoblastic lymphomas is described. This system is based on the tumor score which consists of assigning a point to each one of five variables that have been previously shown to have a high prognostic value. Ann Arbor stages III-IV, presence of bulky mass, elevation of B-2 microglobulin and LDH as well as presence of 'B' symptoms are the variables utilized in this system. When we applied this tumor score system to a population of 144 patients uniformly treated with CHOP/Bleo/CMED protocol, we observed that this system can accurately divide the population into two prognostic groups without an intermediate category. The first group is made up of those patients with a score of 0-2 points while the second group consists of patients with a score of > or = 3 points. The first group has a time-to-treatment failure (TTF) of 83% at three years in contrast to the second group whose TTF was 24%. If we compare this system with other commonly used systems in our institution, such as Ann Arbor, M.D. Anderson clinical staging system, and M.D. Anderson serological staging system, we observed that the tumor score system is not only more specific and sensitive than the others but also was capable of eliminating an intermediate risk group, thus facilitating therapeutic choices. This tumor score system is easy to apply and potentially reproducible in any institution. PMID- 1450061 TI - Severe vascular adverse effects with thrombocytopenia and renal failure following emetogenic chemotherapy and ondansetron. AB - During late 1991, a series of severe adverse events involving thrombocytopenia, renal insufficiency and thrombotic episodes was observed in patients receiving emetogenic chemotherapy. Two patients died, one of renal failure and one of cerebral haemorrhage in the presence of thrombocytopenia. Other severe side effects included thrombosis of the aorta causing paraplegia and multifocal cerebral infarctions. Common exposure features included the use of ondansetron and dexamethasone as antiemetics, and in most of the cases high dose (100 mg/M2 or more) cisplatin. Retrospective review of a series of patients treated with similar cytotoxic regimens for similar diseases before the use of ondansetron revealed no similar adverse effects, but no substantial differences were observed in renal function or haematologic toxicity in the two groups overall. Sporadic adverse vascular events have been observed before the use of ondansetron. The mechanism remains unknown, and it is not clear whether ondansetron was a factor in the unusual incidence of such events in the present series. PMID- 1450062 TI - Sequential estrogen receptor determinations from primary breast cancer and at relapse: prognostic and therapeutic relevance. The International Breast Cancer Study Group (formerly Ludwig Group). AB - We retrospectively evaluated 401 selected patients who had estrogen receptor (ER) assays both at primary surgery and at relapse in an accessible site to determine the clinical relevance of the subsequent ER determination. The median time between ER assessments was 27 months (range: 2-122 months). The median follow-up time from diagnosis was 6 years (range: 2-12 years). For patients with ER+ tumors at primary diagnosis, 29% (76/261) had ER- tumors at relapse, while for ER- primaries, the conversion rate was 33% (46/140). Conversions from ER+ to ER- occurred more often when the time interval between assays was less than one year (p = 0.004), while conversions from ER- to ER+ tended to occur late (beyond three years; p = 0.0003). Treatments received between assays (usually adjuvant therapy) had only a slight influence on ER status conversion. Post-relapse survival was poor for patients who had the biopsy accessible recurrence within one year; an expression of the aggressive nature of the disease. Among patients whose accessible relapse was beyond one year, those with ER- primaries who converted to ER+ had a longer survival than those whose recurrence was classified again as ER- (p = 0.006). This group of patients with ER- primaries who recurred beyond one year with an ER+ tumor in an accessible site represented 29% (40/140) of all patients with ER- primaries and had an estimated overall survival rate of more than 60% at 6 years from the accessible relapse. ER determination upon relapse within one year has very little clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450063 TI - Recombinant tumor necrosis factor for superficial bladder tumors. AB - Twenty patients with histologically documented superficial bladder cancer (Ta, T1, Tis) were treated with intravesical administration of TNF 400-1800 micrograms. Of 18 patients with a marker lesion, 2 obtained a complete response for 8+ and 18 months. Two had a partial response and were given other intravesical therapies after 5 and 7 months. No or minimal systemic absorption of TNF was observed and documented in 4 of 20 patients by pharmacokinetic studies, and no patients developed antibodies to intravesically administered TNF. TNF was well tolerated in doses up to 1800 micrograms. No systemic or local side effects were observed. Modest activity was attained with intravesical TNF, even in pretreated patients. PMID- 1450064 TI - The Stanford experience with combined procarbazine, Alkeran and vinblastine (PAVe) and radiotherapy for locally extensive and advanced stage Hodgkin's disease. AB - This report describes the efficacy and toxicity of PAVe (procarbazine, Alkeran, vinblastine) and irradiation (RT) in the management of 159 patients with locally extensive or advanced stage Hodgkin's disease (HD) at Stanford University. Patients received six courses of chemotherapy alternating with RT. The extent of RT and the schedule of treatment varied according to the stage of disease. About 2/3 of patients received PAVe/RT in the setting of prospective, randomized clinical trials. The rate of complete response was 93%. With a median follow-up of seven years (range 2-17), the 15 year actuarial freedom from progression (FFP) is 78% and overall survival is 75%. Ten-year FFP by stage is: 80% for locally extensive stage II, 90% for stage IIIA and 70% for stage IIIB. Excellent and equal results were attained with PAVe/RT vs. MOP(P) (mustard, Oncovin, procarbazine with or without prednisone)/RT in the randomized combined modality studies. Progression or recurrence was documented in 30 patients and was more common in irradiated sites. PAVe was well tolerated acutely. There were no treatment related fatalities. Twenty-three (14%) patients were admitted to the hospital for neutropenic fever. Five second malignancies have occurred after PAVe/RT only: one myelodysplastic syndrome, one acute myelogenous leukemia, one non-Hodgkin's lymphoma and two solid tumors including a case of non-small cell lung cancer and an in situ carcinoma of the cervix. Three patients died from myocardial infarction several years after the completion of treatment. These mature data show that PAVe/RT is effective and well-tolerated therapy for locally extensive stage II and IIIA/B HD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450065 TI - Preclinical antitumour activity and animal toxicology studies of rhizoxin, a novel tubulin-interacting agent. AB - Rhizoxin is a 16-membered antifungal macrocyclic lactone isolated from the plant pathogenic fungus Rhizopus chinensis. The compound binds to tubulin, preventing microtubule formation, and inhibiting mitosis. It possesses antitumour activity in vivo against various preclinical murine models, both leukaemias and solid tumours model, as well as in vincristine- and doxorubicin-resistant leukaemia lines. In the present study, cytotoxic activity was observed in human tumour cell lines in vitro at very low concentrations (+/- 10(-10) M) particularly against melanoma, colon, renal, non-small cell and small cell lung cancer. In vivo antitumour activity was demonstrated in murine P388 and L1210 murine leukaemias, solid tumour models B16 melanoma and M5076 sarcoma, and in 5 out of 9 human solid tumour xenografts: LOX melanoma, MX-1 breast cancer, non-small cell lung cancer A549, and small cell lung cancers LXFS 605 and LXFS 650. The absence of cross resistance to vinca alkaloids was confirmed in vivo against the vincristine resistant P388 leukaemia subline and the vincristine-resistant human small cell lung cancer LXFS 650. In addition, the antitumour activity of rhizoxin was improved by prolonged or repeated drug administration indicating a schedule dependency. In animal toxicology studies, transient changes in erythrocyte and leukocyte numbers, local phlebitis, diarrhea, and spermatogenic arrest were observed. The LD10 value of rhizoxin after a single intravenous injection was 2.8 mg/kg (8.4 mg/m2). One-tenth of the mouse equivalent LD10 (0.84 mg/m2), the starting dose for clinical phase I studies, was considered to be safe in rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450066 TI - Treatment of primary refractory or relapsed acute lymphoblastic leukemia (ALL) in children. AB - Thirty-one intensively pretreated children with ALL in first bone marrow relapse or refractory to initial therapy were treated with a combination of intermediate dose Ara-C and idarubicin (IDA). Twenty-four patients (77%) achieved complete remission (CR), 8 patients relapsed early and 2 were removed from the study. Fourteen (45% of the original 31 patients) underwent bone marrow transplant (BMT) and 7 of them (22%) are still in continuous CR (CCR) with a median follow-up of 18 months. These results confirm that it is possible to achieve CR even in ALL children who failed on an initial intensive regimen. Newer modalities of post remission therapy, especially for children lacking an HLA donor, should be considered. PMID- 1450067 TI - Metastatic breast cancer: higher versus low dose maintenance treatment when only a partial response or a no change status is obtained following doxorubicin induction treatment. An Eastern Cooperative Oncology Group study. PMID- 1450068 TI - Local treatment of malignant pleural mesothelioma with intracavitary cytosine arabinoside and cisplatin. PMID- 1450069 TI - Ondansetron is not associated with vascular adverse events, thrombocytopenia or renal failure. PMID- 1450070 TI - Can ondansetron hydrochloride (Zofran) enhance the nephrotoxic potential of other drugs? PMID- 1450071 TI - Thyroid, pulmonary, and cardiac sequelae after treatment for Hodgkin's disease. AB - Modern therapy of Hodgkin's disease has produced the expectation of long-term survival for most patients. However, in the process of achieving the current success, a price has been paid in unwanted, delayed side effects. Apart from second malignancies and gonadal impairment, other adverse consequences can be identified. This paper will briefly summarize recent findings related to thyroid, pulmonary and cardiac dysfunction. Attention to treatment regimens and careful follow-up may help to prevent or manage these complications, which are uncommonly life-threatening. The desire to refine the treatment of Hodgkin's disease must not result in a reduction of the overall chance of cure. PMID- 1450072 TI - Second cancer after the treatment for Hodgkin's disease: a report from the International Database on Hodgkin's Disease. AB - Twenty institutions/cooperative groups tabulated second cancers among 12,411 patients diagnosed with Hodgkin's disease between 1960 and 1987, giving 82,850 person-years of observation. Overall, 631 second cancers were observed, as compared with 223.25 expected (observed (O) to expected (E) ratio 2.83, p < 0.001) at least one year after the diagnosis of Hodgkin's disease. Second cancers were acute leukaemias (AL) in 158 cases as compared with 5.75 expected (O/E = 27.48, p < 0.001), non-Hodgkin's lymphomas (NHL) in 106 cases as compared with 3.34 expected (O/E = 31.77, p < 0.001), and solid tumors (ST) in 367 cases as compared with 214.16 expected (O/E = 1.71, p < 0.001), with no differences between males and females. Excess of ST was observed for the following anatomic sites: salivary gland, small intestine, colon, bronchus, pleura, bone, skin other than melanoma and thyroid in males; salivary gland, bronchus, pleura, skin other than melanoma and breast in females. While the excess of second AL and NHL was significant over the 1-14 year period after the start of initial therapy, that of second ST became apparent after the fifth year, increasing with time. Overall, the 15-year cumulative incidence rate of second cancer was 11.2%. It was 2.2%, 1.8% and 7.5% for second AL, NHL and ST, respectively. While the cumulative incidence of AL and NHL plateaued after 17 years, that of ST was still increasing. To analyse whether a particular treatment category was associated with an increased risk of second cancer, a prognostic study was performed on the 11,241 patients who achieved a complete remission and were continuously disease free. Overall, 87 patients developed an AL, 68 a NHL, and 231 a ST. Combined modality treatments including MOPP or MOPP-like chemotherapy were associated with the higher risk of second AL (Relative risk (RR) = 17.11; p < 0.001) followed by age above 50 (RR > 4.50; p < 0.001), advanced clinical stage (RR > 2.50; p < 0.001), splenectomy (RR = 1.65; p < 0.05) and MOPP or MOPP-like chemotherapy used alone (RR = 2.20; p < 0.05). Factors associated with an increased risk of second NHL were age above 30 (RR > 3.5; p < 0.001), male gender (RR = 1.82; p < 0.05) and clinical stage III (RR = 1.70; p < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1450073 TI - Hodgkin's disease: quo vadis? PMID- 1450074 TI - Activation of cytokines in Hodgkin's disease. AB - The complex histological pattern in Hodgkin's disease and in part in large cell anaplastic lymphomas (ALCL) suggests that close interactions exist between the tumor cells and reactive bystander cells. These interactions are most likely mediated by short ranged cytokines. The production of cytokines was analyzed in primary tissues and cell lines from Hodgkin's disease and ALCL by enzyme linked immunosorbent tests (ELISA), Northern blotting, immunohistological staining and in situ hybridization experiments. Our results indicate that Hodgkin's disease derived cell lines produce a variety of cytokines, such as IL1 alpha, IL4, IL5, IL6, IL8, IL9, TNF alpha and TNF beta but not IL1 beta, IL2, IL3 and G-CSF. In addition, the receptors for IL6 were detected in some of the cell lines. The expression of IL6 and IL6 receptors and IL9 has been confirmed for some primary tissues of Hodgkin's disease. From our data, we conclude that IL6, IL9 and additional cytokines are involved in the biology of Hodgkin's disease and ALCL. PMID- 1450075 TI - Cell adhesion molecules in Hodgkin's disease. AB - The fact that Hodgkin's cells are capable of binding lymphocytes has been observed both in vivo and in vitro. It is not unexpected, therefore, that cultured Hodgkin's cells have been found to express a high number of adhesive sites, including representative molecules from various adhesion molecule families. PMID- 1450076 TI - Preliminary report: growth of Hodgkin's lymphoma derived cells in immune compromised mice. AB - Until now there has been no satisfactory animal host for the in vivo growth of Hodgkin lymphoma cells. With the exception of one mutant subline (L540Cy) none of the other Hodgkin derived cell lines nor Hodgkin's disease (HD) derived lymphatic tissue could be propagated in suitable animal systems such as the T-cell deficient nude mouse. Recently, the severe combined immunodeficient (SCID-) mouse has been demonstrated as a possible recipient for human lymphatic tissue. In the present study, we have evaluated the SCID mouse as a possible in vivo model for Hodgkin's lymphoma. I) We demonstrate that seven permanent cell lines derived from patients with Hodgkin's disease grow progressively in SCID mice after subcutaneous and intraperitoneal inoculation. II) In addition, after intravenous injection, two of these lines (L540, L540Cy) show a disseminated growth pattern resembling the distribution of HD cells in man (involvement of lymph nodes, liver and bone marrow but not of spleen). The observed reproducible disseminated tumor growth establishes the SCID mouse as a new animal model for experimental treatment strategies in Hodgkin's lymphoma. III) We present preliminary results of the transplantation of primary material from 13 patients with Hodgkin's disease. Material from two patients induced human tumors in the SCID mice recipients, whereas material from two others led to the induction of mouse lymphomas. The human tumors showed three distinct histological patterns: 1) Lymphoproliferative disease (LPD); 2) anaplastic large cell lymphomas (ALCL); 3) Hodgkin like lesions (HLL). In vitro cell lines established from human SCID mouse tumors were of B-lymphoid origin, were EBV-positive and showed numerical and some structural chromosomal aberrations of varying degree. PMID- 1450077 TI - Histopathological classification of Hodgkin's lymphomas. Results from the reference pathology of the German Hodgkin Trial. AB - Diagnostic biopsies of 1,140 previously untreated patients with Hodgkin's lymphoma from the German Hodgkin Therapy Trial were evaluated by a panel of 4 histopathologists. Each case was classified by consensus of the four according to an extended Rye-System including the diversifying of NS.HD and the unclassifiable cases. The interobserver agreement rate was 92.1% among the panel members regarding the final classification. Primary Hodgkin diagnosis was approved in 91.7% (1045/1140 cases). The distribution of the 1,140 cases within this system was (in %) as follows: 2.7 LP.HD, 57.9 NS.HD, 17.3 MC.HD, 0.7 LD.HD, 13 HD of unclassifiable subtypes, 6.3 of not certain HD, 1.9 Non-Hodgkin Lymphoma, 1 case of non malignancy. Grading of NS.HD into 2 subgroups according to the British classification differed conspicuously by 84.5% versus 15.5% and 71.6% versus 28.4% in British results. This divergency is explained by interobserver disagreement ranking from 43% to 85%. PMID- 1450078 TI - New concepts on histopathology of Hodgkin's disease. PMID- 1450079 TI - Controversies in the use of diagnostic staging laparotomy and splenectomy in the management of Hodgkin's disease. AB - Considerable controversy exists over the routine use of diagnostic staging laparotomy and splenectomy in the workup of patients with Hodgkin's disease. With the development of effective, and perhaps less toxic chemotherapy the need for staging laparotomy has somewhat decreased. In the United States it is still common to recommend surgical staging for early stage patients when the results influence the choice of treatment. Since 20%-30% of clinically staged (CS) IA-IIA and 35% of CS IB-IIB patients with Hodgkin's disease will have occult splenic or upper abdominal nodal involvement not detected by LAG, CT, MRI, or gallium imaging, staging laparotomy allows for selection of patients either to receive limited radiation therapy alone (most PS I-II patients) or chemotherapy with or without radiation (PS III). In Europe, Canada, and South America most patients are clinically staged without a laparotomy. Patients are selected for treatment with radiation therapy alone or for chemotherapy with or without radiation on the basis of clinical prognostic factors. This article details the current arguments for and against the use of staging laparotomy. PMID- 1450080 TI - Diagnostic imaging studies in patients with newly diagnosed Hodgkin's disease. AB - A variety of diagnostic imaging studies are used to evaluate patients with newly diagnosed Hodgkin's disease which provide important information to determine stage and guide patient management. The following will review the current status of diagnostic imaging studies as applied to evaluation of the thorax, abdomen and pelvis, with comment on areas under investigation. PMID- 1450081 TI - International Database on Hodgkin's Disease: a cooperative effort to determine treatment outcome. AB - In an effort to better determine the outcome of patients treated for Hodgkin's disease, twenty institutions/cooperative groups in the western world agreed in 1988 to participate in the development of a large data base by sending data to be analyzed by a common statistical design. Data was obtained from both patients randomized on prospective trials and patients treated by standard protocol but not randomized. Overall statistics on 14,315 adult patients treated from the early 1960s to 1987 were collected. This data was first presented at the Paris International Workshop and Symposium held on June 28-30, 1989. The proceedings, published in 1990, include a detailed description of the data, and prognostic studies on laparotomy findings, response to initial therapy, relapse-free survival, overall survival, and secondary malignancies. The International Database on Hodgkin's Disease represents a compromise between two more classical approaches such as the use of randomized trials and metaanalyses. It should serve as a model for the study of other types of cancer. It has been successful because of interest, time, and the cooperation of physicians in academic centers from much of the western world. PMID- 1450082 TI - Current therapeutic strategies in Hodgkin's disease. PMID- 1450083 TI - Hodgkin's disease in 92 patients with HIV infection: the Italian experience. GICAT (Italian Cooperative Group on AIDS & Tumors). AB - Ninety-two cases of Hodgkin's disease (HD) in patients with HIV infection have been collected by the Italian Cooperative Group on AIDS and Tumors (G.I.C.A.T.). In accordance with the epidemiology of HIV infection in Italy, 82% were intravenous drug users (IVDU), 8% homosexual men, 5% IVDU+homosexuals and 5% heterosexuals. At diagnosis of HD, 16% had AIDS, 20% AIDS related complex (ARC), 33% persistent generalized lymphadenopathy (PGL) and 31% were asymptomatic. Fifty three percent of the patients had stage IV disease and 70% mixed cellularity and lymphocytic depletion. Forty-six patients were treated with MOPP or MOPP [symbol: see text] ABVD +/- radiotherapy (zidovudine was not given) with complete remission (CR) in 54% and partial remission (PR) in 46% of the patients. Fifty six percent of these patients developed opportunistic infections (OI) during therapy or follow-up. Sixteen patients were treated with epirubicin, bleomycin and vinblastine (EBV) and concomitant zidovudine, with CR in 44% and PR in 38%. However, only one of these patients developed OI during therapy or follow-up. The clinico-pathological features and natural history of HD in HIV setting are peculiar and quite distinct from those observed in HD in the general population. Better combined chemotherapy and antiretroviral therapy is needed in order to ameliorate the CR rate and decrease the OI in patients with HIV infection and HD. PMID- 1450085 TI - Radiotherapy versus combined modality in early stages. AB - In early stage Hodgkin's disease the optimal choice of treatment for the individual patient is still an unresolved issue. So far, twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out worldwide. The preliminary results of a global metaanalysis of these trials indicate that we still do not definitively know whether or not the addition of prophylactic chemotherapy up front improves survival. Arguments in favour of the addition of chemotherapy up front are: that laparotomy may be avoided, that radiation fields and doses may perhaps be reduced, and that the stress of experiencing a relapse is avoided in many patients. The major argument against the use of chemotherapy up front is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may be kept at a minimum. Recently, trials have been carried out testing chemotherapy alone. The results of these trials are however conflicting. In order not to jeopardize the good results achieved with the standard treatments developed over the last three decades, newer treatment approaches should be carefully tested in large randomized trials before being implemented for general clinical use. PMID- 1450084 TI - Treatment of children with Hodgkin's disease--results of the German Pediatric Oncology Group. AB - Six hundred sixty-seven children under age 16 were enrolled in 4 consecutive studies in West Germany between 1978 and 1990. These trials were mainly designed to reduce the long-term sequelae of high dose extended-field irradiation as well as the late effects of chemotherapy, in the context of combined modality treatment for all stages. Treatment concepts and results of studies HD-82, HD-85 and HD-87 are presented here. Patients with stages IA/B and IIA were treated with 2 cycles of OPPA (HD-82, n = 100) or OPA without procarbazine (HD-85, n = 53; HD 87, n = 104), followed by involved field irradiation (IFI) using 35 Gy (HD-82, HD 85) or 30 Gy (HD-87). Kaplan-Meier estimates (KME) for event-free survival (survival) at 4.5 years are 99% (100%) in HD-82, 85% (98%) in HD-85 and 88% (100%) in HD-87. Thus, 2 x OPPA is a highly effective chemotherapy eradicating occult microfoci in the non-irradiated adjacent fields, whereas 2 x OPA is less efficacious. Reduction of the radiation dose to 30 Gy (IFI) within the combined modality concept does not affect treatment outcome. About 30% of the boys treated with 2 x OPPA, but none of the girls and none of the boys treated without procarbazine (PC) showed elevated FSH-levels indicating gonadal dysfunction. No secondary leukemias and preleukemias were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450086 TI - NOVP and radiotherapy for early-staged Hodgkin's disease: an interim analysis. AB - Modern treatment plans for early staged Hodgkin's disease must focus on optimal disease-free survival results without laparotomy, minimal acute toxicity, and reduced long-term complications. We have treated 69 adult patients with stage I II Hodgkin's disease, 40 of whom had bulky disease, B symptoms, or hilar disease, and 22 with stage III disease with 3 cycles of NOVP (Novantrone, vincristine, vinblastine, prednisone) and radiotherapy. Only patients with stage III1 disease involving the celiac axis without para-aortic or pelvic involvement, had to undergo laparotomy prior to treatment. Three patients did not respond to NOVP: two of these did not respond to MOPP or ABDIC, and two are currently without relapse following bone marrow transplant. With a median follow-up of 18 months, 62 with stage I-II and 19 with stage III remain without relapse, and 91 patients are alive. Tolerance to therapy was excellent with minimal nausea, myalgias, and alopecia. We conclude that this regimen for Hodgkin's disease provides good results for clinically staged I-III disease, but longer follow-up may demonstrate prognostic factors which will influence our results. PMID- 1450087 TI - Conceptual problems in relation to dose escalation in the first remission of Hodgkin's disease. AB - Autologous bone marrow transplantation (ABMT) is now widely used as salvage therapy in Hodgkin's disease but its value will have to be finally proved by the use of randomised trials. However ABMT is now being used in first remission. The justification of this is based on the view that patients can be identified once remission is achieved who are at high risk of relapse and that these patients will be prevented from relapsing by high dose therapy and ABMT in first remission with an 'acceptable' procedure related toxicity. The choice of patients judged to be suitably poor risk is critical but unproven. The only report of ABMT in CR1 yet published [1] is encouraging but can be criticised on a number of grounds. The incidence of procedure related mortality is a significant factor in determining the balance of any risk/benefit analysis. Randomised trials need to be undertaken but must identify the correct group of patients to avoid treating with high dose therapy those who may already have been cured by initial therapy. PMID- 1450088 TI - Autologous bone marrow transplantation for Hodgkin's disease. AB - Autologous bone marrow and/or peripheral blood stem cell transplantation is being performed increasingly frequently as a treatment for Hodgkin's disease. While patients with refractory disease can sometimes be cured, the results are better in patients who are still chemotherapy sensitive. The use of high dose therapy as part of the primary treatment for high risk patients is now being studied. PMID- 1450089 TI - Digitalis and heart failure: does digitalis really produce beneficial effects through a positive inotropic action? AB - Although digitalis was introduced to medicine long ago, the drug is still extensively used in clinical practice today. Opinions on its mechanism of action have undergone much change in the course of time, and the way in which cardiovascular effects are produced is still not completely clear. Limitations and contraindications for the use of digitalis substances are reported, especially in the treatment of ischemic heart disease. Preliminary data regarding the effects of digitalis on the diastolic phase are unfavorable, although the relationship between digitalis and diastolic function ought to be studied in greater depth in various clinical conditions. In spite of many recent trials, the old question of the usefulness of digitalis in the chronic treatment of patients in sinus rhythm and heart failure is still debated. An important clinical benefit in the chronic use of digitalis appears restricted to a relatively small proportion of patients with severe congestive heart failure, while in the majority of chronically treated subjects the effects of the drug are scanty or insignificant. The beneficial effect of digitalis used chronically is essentially believed to be due to its positive inotropic action. Since the vagomimetic and the antiadrenergic effects of digitalis have been demonstrated to be independent from its inotropic action, they could be considered determinants of the clinical benefits of digitalis. These indirect effects may be useful in the control of the negative neuroendocrine response developing during congestive heart failure. Thus the statement that digitalis is essentially an inotropic agent seems restrictive; its definition should reflect the favorable effects obtained in some cases of congestive heart failure rather than its various and contrasting underlying mechanisms of action. PMID- 1450090 TI - A comparison of the effects of captopril and flosequinan in patients with severe heart failure. AB - Angiotensin converting enzyme inhibitors have greatly improved the treatment of patients with chronic heart failure but they are not effective in all patients, and their use may be limited by side effects. There is, therefore, a need to investigate new drugs and to compare their efficacy with angiotensin converting enzyme inhibitors. Flosequinan is a new direct-acting vasodilator that has been shown to be effective in placebo-controlled studies. Patients with chronic heart failure in NYHA classes II or III who remained symptomatic despite at least 80 mg of frusemide daily were recruited from two centers. Following a single-blind placebo run-in period, the patients were randomized double blind to either the addition of captopril or flosequinan for 6 weeks. Following a further 2-week placebo washout period, they were then given the alternative treatment. Symptom limited treadmill exercise times, scores of perceived exertion, and corridor walk tests were measured at two weekly intervals during the study. Twenty-five patients entered the study, 16 of whom completed without a change in diuretic dose. Five patients were withdrawn while taking captopril and two while taking flosequinan; two were withdrawn during the placebo washout period. For those patients who completed the study, flosequinan increased treadmill exercise tolerance from a mean (SEM) placebo time of 11.5 (1.0) minutes by 2.4 (0.6) (p = 0.0002) and captopril from 12.0 (0.8) minutes by 1.2 (0.6) minutes (p = 0.08). Comparison of the other measures of efficacy revealed no difference between the groups. In this short-term study flosequinan appeared to be equal in efficacy to captopril. PMID- 1450091 TI - A multicenter comparison of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in patients with ischemic heart disease. AB - The effects of nicorandil and diltiazem on serum lipid, apolipoprotein, and lipoprotein levels in 37 patients with ischemic heart disease were examined in a randomized, multicenter study. Nicorandil (n = 20, 10-40 mg/day, b.i.d.) and diltiazem (n = 17, 60-240 mg/day, b.i.d.) were administered for 12 weeks. Both nicorandil and diltiazem administration showed an effective antianginal effect. Diltiazem administration showed a significant hypotensive action. There were no significant changes in serum lipids, apolipoproteins, and lipoproteins for both nicorandil and diltiazem. There were no significant changes in body weight, uric acid, and fasting blood sugar levels during the test period for both drugs. These data show that nicorandil, like diltiazem, does not have any adverse effects on lipid metabolism and that it is a favorable drug to use as an agent for treating arteriosclerotic heart disease. PMID- 1450092 TI - Intravenous atenolol in elderly patients in the early phase of acute myocardial infarction. AB - The aim of this study was to assess the hemodynamic response to intravenous atenolol in elderly patients with acute myocardial infarction. We studied 14 elderly men, aged 64-85 years, and 14 younger men, aged 29-48 years, in the early postfibrinolytic phase of acute myocardial infarction. All the patients were in Killip class I. A triple-lumen Swan-Ganz thermodilution catheter was introduced into the right heart chambers. The patients received 5 mg intravenous atenolol over 5 minutes. All hemodynamic parameters were measured before and 10 minutes after atenolol. The hemodynamic characteristics and the location and extent of acute myocardial infarction were the same in both groups before atenolol. The hemodynamic changes after atenolol administration were the same in the two groups, but the stroke volume and cardiac indexes decreased to a greater extent in the elderly (p = .01 and p = .0001, respectively). These results indicate that intravenous atenolol in the early postfibrinolytic phase of acute myocardial infarction is safe in Killip class I elderly patients, although the cardiac and stroke volume indexes decrease, and the increase in the total systemic resistance is more in older than in younger patients. PMID- 1450093 TI - Antianginal effects of amlodipine at a single dose on exertional angina patients using treadmill exercise testing--a randomized crossover study in comparison with placebo. AB - With eight cases of stable exertional angina as subjects, the antianginal action and sustained effects of single 10 mg oral doses of new calcium antagonists amlodipine were assessed by treadmill exercise tests in randomized crossover trials with respect to a placebo. Exercise tests were conducted before as well as 4, 8, and 24 hours after administration, and plasma amlodipine concentration was investigated at the same times. The maximal exercise time was 299 +/- 43 seconds before as compared with 346 +/- 49 seconds 4 hours after administration and 368 +/- 50 seconds 8 hours after administration, a significant prolongation in each case (p < 0.01). Moreover, the exercise time elapsed until 1 mm of ST-segment depression, as well as the ST-segment depression measured at the same time, were both significantly improved as compared with the placebo results. The plasma amlodipine concentration reached a peak 8 hours after administration and displayed an effective level even 24 hours after administration. The value of delta PRP measured at the same time during the exercise test was also significantly reduced as compared with the placebo results, even 24 hours after administration of amlodipine. These findings supported the conclusion that single 10-mg doses of amlodipine provide stable antianginal action over a 24-hour period. PMID- 1450094 TI - Comparison of effects of enalapril and captopril on serum potassium concentration in the treatment of malignant hypertension. AB - To compare the effects of enalapril and captopril on blood pressure, serum creatinine (S-Cr), and potassium (S-K) levels, patients with malignant hypertension treated with either 5-10 mg of enalapril (eight cases) or 75-400 mg of captopril (eight cases) were investigated retrospectively. After 2 weeks of treatment, the average blood pressure fell from 214/138 to 132/89 mmHg on enalapril and from 240/145 to 147/95 mmHg on captopril. The percent change in mean blood pressure during the 2 weeks of treatment with enalapril (-35.6 +/- 4.0 SE%) was similar to that with captopril (-35.8 +/- 2.8%). S-Cr did not change in both groups, while S-K increased significantly from 3.9 +/- 0.2 to 5.2 +/- 0.2 mEq/l on enalapril and from 3.6 +/- 0.2 to 4.2 +/- 0.1 mEq/l on captopril. S-K at the second week was significantly higher in the enalapril than in the captopril group. The maximum S-Cr concentration during the treatment was correlated with the corresponding S-K concentration similarly in both groups. These results indicate that both enalapril and captopril increase S-K without deterioration of renal function in patients with malignant hypertension and that the way these drugs are used in clinical practice may be more likely to result in elevated S-K with enalapril. PMID- 1450095 TI - Inhibition of platelet accumulation by beta 1-adrenoceptor blockade in the thoracic aorta of rabbits subjected to experimental sympathetic activation. AB - Arterial platelet adhesion is an initiating event in the thrombo-embolic complications of atherosclerosis and may also accelerate the development rate of atherosclerotic lesions. Psychosocial stress has been shown to accelerate atherogenesis in animals, an effect probably mediated via beta-adrenoceptor activation. In view of the postulated roles of platelets and beta-adrenoceptor activation in atherosclerosis development, we decided to test whether beta blockade affects arterial platelet accumulation. We studied the accumulation of radioactivity from 111In-labelled platelets on the wall of the thoracic aorta of rabbits as a measure of platelet accumulation. During the exposure to the labelled platelets, the animals were also exposed to 3 hours of chloralose anesthesia. This is a reproducible model of experimental sympathetic activation, including beta-adrenoceptor activation, which we used to amplify possible effects of beta-blockade on platelet-vessel wall interaction. The effectiveness of the anesthesia in increasing sympathetic activity was verified by significant rises in mean arterial blood pressure (from 77 to 88 mmHg), heart rate (190 to 290 bpm), and plasma levels of norepinephrine (1.0 to 3.3 nM) and epinephrine (0.13 to 0.83 nM). In chloralose anesthetized rabbits, approximately 30 x 10(-9)% of the injected 111In accumulated in each square millimeter of intima at unbranched thoracic aorta. Platelet accumulation was significantly higher at arterial branching points, 70% higher at intercostal artery bifurcations, and 150% higher at coronary artery bifurcations than in unbranched aortic intima. Pretreatment with metoprolol in a dose resulting in "therapeutic" plasma levels significantly reduced platelet accumulation by 48% in unbranched aorta, 65% at intercostal, and 53% at coronary artery bifurcations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450096 TI - Comparative class 1 electrophysiologic and anticholinergic effects of disopyramide and its main metabolite (mono-N-dealkylated disopyramide) in healthy humans. AB - During steady-state treatment with disopyramide, its main and active metabolite, mono-N-dealkylated disopyramide, was reported to reach concentrations that were equal to or higher than the parent drug in 25% of 70 evaluated patients. This metabolite has been found to have a more pronounced anticholinergic action than the parent drug on in vitro evaluation, but neither its anticholinergic nor its direct electrophysiologic effects on the human heart have been properly assessed. We therefore compared the acute electrophysiologic and anticholinergic effects (the standard being atropine, 0.04 mg/kg) of disopyramide and its main metabolite, given 2 mg/kg body weight intravenously to 10 healthy individuals in a double-blind, randomized, crossover design. The anticholinergic effect of these substances on sinus and atrioventricular node function was unexpectedly found to be of similar magnitude and more pronounced than previously thought (at least one third the effects of the atropine dose). The class 1 electrophysiologic effects were as follows: intra-atrial and His-Purkinje conduction (the PA and the HV interval, respectively) was prolonged 33% (95% CI: 18-47%) and 27% (21-32%) by disopyramide, and 15% (10-19%) and 13% (10-17%), respectively, by the metabolite. Disopyramide also prolonged the QRS, JT, and QT intervals by 15% (9-21%), 10% (8 13%), and 10% (7-12%), respectively. The metabolite caused a 9% (7-12%) prolongation of the QRS interval (significantly less than disopyramide), but shortened repolarization (as reflected by the JT interval) by -7% (-2 to -11%; p < 0.01), which is similar to the acute effects of lidocaine 2 mg/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450097 TI - Stimulation of peroxidative reactions by a high dose of allopurinol in the rat myocardium. PMID- 1450098 TI - Effects of celiprolol on cardiovascular responses to smoking in normotensive smokers. PMID- 1450099 TI - Half-squaring in responses of cat striate cells. AB - Simple cells in striate cortex have been depicted as rectified linear operators, and complex cells have been depicted as energy mechanisms (constructed from the squared sums of linear operator outputs). This paper discusses two essential hypotheses of the linear/energy model: (1) that a cell's selectivity is due to an underlying (spatiotemporal and binocular) linear stage; and (2) that a cell's firing rate depends on the squared output of the underlying linear stage. This paper reviews physiological measurements of cat striate cell responses, and concludes that both of these hypotheses are supported by the data. PMID- 1450100 TI - Electrophysiological sensitivity of carotenoid deficient and replaced Drosophila. AB - R1-6 dominated electroretinographic (ERG) spectral sensitivities were determined as a function of days posteclosion from carotenoid deprived and replaced white eyed Drosophila. The sensitivity of flies deprived from egg to adult waxed (about 1.5 log units by day 3), and then waned gradually from 3-11 days (over 2 log units by day 11). Carotenoid replacement (feeding nothing but carrot juice) effected recovery to near the replete controls' level in about 1 day throughout (tested at 0, 4, and 11 days). The normal yellow cornmeal-agar-molasses-brewers yeast fly food (in our laboratory, supplemented with beta-carotene) renders a slower recovery (requiring 7-9 days) since it is a medium designed largely for larval growth. Placing replete adults on deprivational medium did not create a deprivational syndrome in over 11 days. At 3-7 days, deprived flies reared and maintained in constant darkness had substantially enhanced sensitivity, beyond the 1.5 log unit increment already described for cyclic light rearing conditions. All spectral analyses are consistent with the ultraviolet (UV) sensitization of the blue (480 nm) rhodopsin by a replacement-dependent retinoid including two unexpected findings: (1) sensitivity recovery with carrot juice was so fast that the UV peak was already high at 6 h; and (2) the waxing of the deprived fly's sensitivity in dark rearing was so great that the UV peak was present at 4-7 days. PMID- 1450101 TI - Monocular enucleation reduces immunoreactivity to the calcium-binding protein calbindin 28 kD in the rhesus monkey lateral geniculate nucleus. AB - The calcium-binding proteins calbindin (CaBP) and parvalbumin (PV) are important in regulating intracellular calcium in brain cells. PV immunoreactivity is reduced by enucleation in the lateral geniculate nucleus (LGN) and by enucleation and visual deprivation in the striate cortex of adult monkeys. The effects of enucleation and visual deprivation on CaBP immunoreactivity in the LGN are not known. We therefore have studied cells and neuropil in the LGN that are labeled by antibodies to CaBP in normal and visually deprived Rhesus monkeys to determine if there is an effect on this calcium-binding protein. One group of monkeys had one eye removed 2 weeks to 4.3 years before sacrifice. A second group had one eye occluded with opaque lenses from infancy without enucleation. A final group had one eye occluded long-term followed by short-term enucleation 2 weeks before sacrifice. In normal monkeys, CaBP-immunoreactive neurons were found throughout the LGN. They were sparsely distributed within the six main laminae, and more densely distributed within layer S and the interlaminar zones (ILZ). The labeled ILZ neurons had a distinct morphology, with fusiform somata and elaborate dendritic trees that were confined primarily to the ILZ. Most CaBP-labeled neurons in the main layers had dendrites that radiated in all directions from the soma. ILZ and main layer cells labeled by CaBP thus probably represent two different cell types. Monocular enucleation with or without occlusion produced a significant reduction in antibody labeling in the deafferented laminae. Field measures revealed an average 11.5% reduction in optical density in each deafferented lamina compared to its adjacent, nondeprived layer. The differences in field optical density between deprived and nondeprived layers were statistically significant. CaBP neurons were still visible, but the optical density of antibody labeling in these cells also was reduced. Occlusion without enucleation had no effect. Thus, deafferentation, but not light deprivation, reduces concentrations of CaBP in monkey LGN. This effect is different than that seen in striate cortex of adult monkeys, where visual deprivation as well as enucleation alters CaBP immunoreactivity. PMID- 1450102 TI - A circadian clock in the Limulus brain transmits synchronous efferent signals to all eyes. AB - A circadian clock in the brain of the horseshoe crab, Limulus polyphemus, has an important role in the function of the peripheral visual system. At night, the clock transmits neural activity to the lateral, ventral, and median eyes via efferent optic nerve fibers. The activity occurs in synchronous bursts (maximum rate of 2 bursts/s) with individual efferent fibers contributing a single spike in each burst. The circadian efferent activity originates in the protocerebrum. Lateral connections synchronize the efferent activity recorded from the two halves of the protocerebrum, suggesting the existence of bilateral circadian oscillators. Circadian efferent activity survives excision of the brain and isolation of the protocerebrum. We conclude that circadian clock and its complex neural circuitry are fundamental components of the Limulus visual system. PMID- 1450103 TI - Direction selectivity of cells in the cat's striate cortex: differences between bar and grating stimuli. AB - We have investigated the notion that directional responses of cells in the visual cortex depend on the type of stimulus used to drive the cell. Specifically, we have asked if sinusoidal gratings provide a different estimate of direction selectivity than bars that are brighter or darker than the background. Using standard techniques, we recorded from 176 cells in the visual cortex of nine cats. For each cell, bright bars, dark bars, and sinusoidal gratings were presented in a randomly interleaved fashion. Complex cells exhibited around twice as many direction-selective as nondirection-selective responses. Estimates of direction selectivity were nearly identical for bright and dark bars and for gratings. For simple cells, a similar ratio of direction-selective to nondirection-selective responses was observed for gratings. However, a larger proportion of simple cells were classified as direction selective when bars were used for stimulation. A simple cell that exhibited direction selectivity to a grating behaved in a similar manner when stimulated with bright or dark bars. However, in contrast to complex cells, some simple cells classed as directionally nonselective on the basis of their responses to gratings, displayed directionally selective behavior to bars. In addition, the preferred directions for dark and bright bars sometimes differed. These results demonstrate that the classification of a simple cell as directionally selective or nonselective can depend critically on the visual stimulus used. PMID- 1450104 TI - The effect of contrast on the visual response of lagged and nonlagged cells in the cat lateral geniculate nucleus. AB - The response vs. contrast characteristics of different cell classes in the dorsal lateral geniculate nucleus (LGN) were compared. The luminance of a stationary flashing light spot was varied stepwise while the background luminance was constant. Lagged X cells had lower slope of the response vs. contrast curve (contrast gain), and they reached the midpoint of the response range over which the cells' response varied (dynamic response range) at higher contrast than nonlagged X cells. These results indicated that nonlagged cells are well suited for detection of small contrasts, whereas lagged cells may discriminate between contrasts over a larger range. The contrast gain and the contrast corresponding to the midpoint of the dynamic response range were similar for X and Y cells. The latency to onset and to half-rise of the visual response decreased with increasing contrast, most pronounced for lagged cells. Even at the highest contrasts, the latency of lagged cells remained longer than for nonlagged cells. For many lagged cells, the latency to half-fall decreased with increasing contrast. It is shown that the differences in the response vs. contrast characteristics between lagged and nonlagged X cells in the cat are similar to the differences between the parvocellular and magnocellular neurones in the monkey. PMID- 1450105 TI - Changes in fiber organization within the chiasmatic region of mammals. PMID- 1450106 TI - Steady discharges of X and Y retinal ganglion cells of cat under photopic illuminance. AB - The discharges of ON- and OFF-center X and Y retinal ganglion cells in the presence of stationary patterns or of a uniform field of photopic luminance were recorded from urethane-anesthetized adult cats. The interval statistics and power spectra of these discharges were determined from these discharge records. The patterned stimuli were selected and positioned with respect to a cell's receptive field so as to generate steady discharges that were different in mean discharge rate from that cell's discharge for the diffuse field. The interval statistics of discharges recorded for diffuse or patterned illumination for all cell types can be modeled, approximately, as coming from renewal processes with gamma distributed intervals. The gamma order of the interval distributions was found to be nearly proportional to the mean discharge rate for X cells, but not for Y cells. Typical values for the gamma orders and their dependence on mean rate for different cell types are given. The same model of a renewal process with gamma distributed intervals is used to model the measured power spectra and performs well. When the gamma order is proportional to mean rate, the power spectral density at low temporal frequencies is independent of discharge rate. Gamma order was proportional to mean rate for X cells but not for Y cells. Nonetheless, the power spectral densities of both cell types at low frequencies were approximately independent of discharge rate. Hence, noise in this band of frequencies can be considered additive. The consequences of departures from the renewal process and of the gamma order not being proportional to mean rate are considered. The significance of different rates of discharge for signaling is discussed. PMID- 1450107 TI - The relative time course of axonal loss from the optic nerve of the developing guinea pig is consistent with that of other mammals. AB - The relative timing of a number of events during the development of the visual system has recently been suggested to be consistent across a number of mammalian species (Dreher & Robinson, 1988). Some conflicting reports, however, had suggested that the precocial guinea pig might represent an exception to the generalized scheme. A quantitative study was thus carried out on the development of the optic nerve and retina of the guinea pig. Consistent with the prediction of a stable relative time course of mammalian visual development, axons and growth cones were found in the optic stalk from the 24th postconceptional day (40% of the period from conception to eye opening--the cecal period), the peak number of axons was observed on the 32nd postconceptional day (56% of the cecal period), and the phase of rapid axonal loss extended to the 39th and 42nd postconceptional days (68-74% of the cecal period). The number of axons in the adult optic nerve (117,000) represented about 37% of the peak number of axons. Additional observations indicated that during development of the optic nerve the mean axonal diameter increased approximately threefold from 0.31 microns to 1.06 microns. As in other mammals studied so far, myelination was first noted after the period of rapid axonal loss and continued until in the adult 97% of axons were found to be myelinated. In the retina, the presence of pyknotic profiles in the ganglion cell layers extends throughout the periods of loss of the optic nerve axons. Finally, the presence of pyknotic profiles in the amacrine sublayer suggest that in the guinea pig, as in other mammalian species, there is a loss of displaced amacrine cells as well as ganglion cells from the ganglion cell layer. PMID- 1450108 TI - Motion defined exclusively by second-order characteristics does not evoke optokinetic nystagmus. AB - We showed high-contrast, second-order motion stimuli to subjects whilst recording their horizontal eye movements. These stimuli were very poor at evoking optokinetic nystagmus. Smooth-pursuit eye movements and fixation were reduced by a masking band +/- 2.5 deg above and below an imaginary fixation point. First order stimuli evoked vigorous optokinetic nystagmus (OKN) under identical conditions and also when matched for apparent contrast. These findings are discussed in terms of the site of detection of second-order motion. PMID- 1450109 TI - The Limulus-eye view of the world. AB - The compound lateral eye of the adult horseshoe crab, Limulus polyphemus, views the world with approximately 1000 ommatidia. Their optical properties and orientation determine the eye's resolution, field of view, and light collecting ability. Optic axes of adjacent ommatidia diverge from 1-15 deg with an average value of 5.5 deg yielding an average resolution of 0.1 cycles/deg. Resolution is not uniform across the eye: along horizontal planes, it is maximal in the anterior region of the eye (0.22 cycle/deg) and minimal in the posterior region (0.07 cycle/deg); along vertical planes, it is maximal near or just below the horizon (0.23 cycle/deg) and minimal above the horizon (0.04 cycle/deg). Together the ommatidia of one eye view approximately 60% of the hemispheric world on one side of the body. There is little binocular overlap (< 1% of total field). Ommatidial facets of up to 320 microns in diameter (among the largest known in the animal kingdom) make the eye a superb light collector. Limulus are known to use vision to find mates both day and night. Apparently, the optics of the lateral eye sample a large enough part of the world with sufficient resolution and light-collecting ability for the animal to succeed at this essential task. PMID- 1450110 TI - Visual responsiveness and direction selectivity of cells in area 18 during local reversible inactivation of area 17 in cats. AB - We have investigated the effects of inactivation of localized sites in area 17 on the visual responses of cells in visuotopically corresponding regions of area 18. Experiments were performed on adult normal cats. The striate cortex was inactivated by the injection of nanoliters of lidocaine hydrochloride or of gamma aminobutyric acid (GABA) dissolved in a staining solution. Responses of the simple and complex cells of area 18 to optimally oriented light and dark bars moving in the two directions of motion were recorded before, during, and after the drug injection. Two main effects are described. First, for a substantial number of cells, the drug injection provoked an overall reduction of the cell's visual responses. This nonspecific effect largely predominated in the complex cell family (76% of the units affected). This effect is consistent with the presence of long-range excitatory connections in the visual cortex. Second, the inactivation of area 17 could affect specific receptive-field properties of cells in area 18. The main specific effect was a loss of direction selectivity of a number of cells in area 18, mainly in the simple family (more than 53% of the units affected). The change in direction selectivity comes either from a disinhibitory effect in the nonpreferred direction or from a reduction of response in the preferred direction. It is proposed that the disinhibitory effects were mediated by inhibitory interneurones within area 18. In a very few cases, the change of directional preference was associated with a modification of the cell's response profile. These results showed that the signals from area 17 are necessary to drive a number of units in area 18, and that area 17 can contribute to, or at least modulate, the receptive-field properties of a large number of cells in the parastriate area. PMID- 1450111 TI - ATP-independent deactivation of squid rhodopsin. AB - Deactivation of light-activated squid rhodopsin was studied in vitro using GTP gamma S binding by G-protein as a direct measure of rhodopsin activity. Deactivation was inhibited by dilution of the retinal suspension or by removal of soluble components. Deactivation could be restored by addition of soluble material to washed membranes. These results indicate that the deactivation is not due entirely to a conformational transition within rhodopsin itself, but depends on the interaction with other molecules. The possibility that phosphorylation is involved in the deactivation was studied. Deactivation occurred in the presence and absence of added ATP. Deactivation also occurred in the presence of kinase inhibitors and after addition of apyrase, which reduced residual ATP levels to below 1 microM. These results indicate that light-induced phosphorylation is not required for deactivation of squid rhodopsin. In this regard deactivation of squid rhodopsin is different from that of vertebrate rhodopsin, which requires phosphorylation. PMID- 1450112 TI - Morphogenesis of retinal ganglion cells during formation of the fovea in the Rhesus macaque. AB - The morphology of retinal ganglion cells within the central retina during formation of the fovea was examined in retinal explants with horseradish peroxidase histochemistry. A foveal depression was first apparent in retinal wholemounts at embryonic day 112 (E112; gestational term is approximately 165 days). At earlier fetal ages, the site of the future fovea was identified by several criteria that included peak density of ganglion cells, lack of blood vessels in the inner retinal layers, arcuate fiber bundles, and the absence of rod outer segments in the photoreceptor layer. Prior to E112, the terminal dendritic arbor of retinal ganglion cells within the central retina extended into the inner plexiform layer and were located directly beneath their somas of origin or at most were slightly displaced from it. For example, at E90 the mean horizontal displacement of the geometric center of the dendritic arbor from the somas of cells within 600 microns of the estimated center of the future fovea was 4.1 microns (S.D. 2.7, range 1.0-10.0, n = 97). Following formation of the foveal depression the dendritic arbors of cells were significantly displaced from their somas. For example, at E138 the mean displacement was 41.2 microns (S.D. 12.2, range 12.0-56.0, n = 97). The displacement of the dendritic arbor which occurred during this period was not accounted for by areal growth of the dendritic arbor, the somas, or the retina, but was produced by the lengthening of the primary dendritic trunk. Moreover, no significant displacement was observed within the remaining 1.5-6.5 mm of the central retina. These observations provide evidence supporting early speculations that the formation of the foveal pit occurs, in part, by the radial migration of ganglion cells from the center of the fovea during its formation. Our analyses suggest that this migration occurs by the lengthening of the primary dendrite presumably by the addition of membrane. This migration is in a direction opposite to the inward movement of photoreceptors that occurs during late fetal and early postnatal periods (Packer et al., 1990, Journal of Comparative Neurology 298, 472-493). PMID- 1450113 TI - Spectral sensitivity of monocularly deprived cats. AB - The reports of rod-dominated psychophysical spectral sensitivity from the deprived eye of monocularly lid-sutured (MD) monkeys are intriguing but difficult to reconcile with the absence of any reported deprivation effects in retina. As most studies of MD retina have been from cat, we have examined psychophysically the increment threshold spectral sensitivity of MD cats using both reaction time and simultaneous two-choice behavioral procedures. Although the deprived eyes exhibited an absolute increment threshold sensitivity deficit, both rod and cone spectral sensitivity functions were obtained on large white backgrounds. This normal transition from rod to cone vision, as background luminance increased, was also found in threshold vs. intensity functions. Using their deprived eye, some cats exhibited a rod spectral sensitivity function when a smaller, normally photopic, background was used providing some support for a hypothesis that the rod-dominated spectral sensitivity observed in monkey may represent detection of scattered stimulus light. Alternatively monocular deprivation may reveal a rod dominated mechanism which exists in monkey but not in cat. PMID- 1450114 TI - Innovators develop solid state lasers for refractive surgery. PMID- 1450115 TI - An independent evaluation of second generation suction microkeratomes. AB - BACKGROUND: Microkeratome designs for lamellar refractive surgery have changed significantly in recent years. Three microkeratome systems (Automatic Corneal Shaper (Steinway Instrument Company, Inc, San Diego, Calif), Draeger Lamellar Keratome (Storz Instrument GmbH, Heidelberg, Germany), and Microprecision test model (Microprecision Instrument Company, Inc, Phoenix, Ariz) were subjected to a concurrent and independent evaluation. METHODS: Three types of keratectomies (primary superficial stromal, secondary intrastromal, and primary deep stromal) were performed under identical conditions in human cadaver eyes. The resected discs and the beds were observed for uniformity, accuracy, centering, and smoothness. Scanning electron microscopy of the corneal beds and cutting blades was done. RESULTS: The three systems produced irregular surfaces with chatter lines that appeared least rough with the Draeger rotating machine. The average primary and secondary section diameters were undersized by 10% in all three systems. The average primary keratectomy thickness was more accurate with Steinway, but the variability was over 20 microns in all three systems. Regarding the average secondary keratectomy thickness, Steinway tended to cut thicker, whereas Draeger and Microprecision tended to cut thinner than attempted. The Draeger blade presented the smoothest edge. CONCLUSIONS: All three systems need substantial improvements to produce more accurate, reproducible, and smooth resections. More reliable methods to accurately measure the thickness of the resected cornea should be developed. PMID- 1450116 TI - Predicting visual performance following excimer photorefractive keratectomy. AB - BACKGROUND: A duplex optical image is created when the ablation zone formed by excimer photorefractive keratectomy is smaller than the entrance pupil. Visual performance and secondary effects are analyzed using a theoretical model of the optical image. METHODS: A point-spread function having a centered in-focus component surrounded by an annular out-of-focus component is calculated from pupil size, ablation size, refractive error, and photoreceptor directional sensitivity. The line-spread, edge-spread, and optical transfer functions are derived. RESULTS: In the line- and edge-spread functions, secondary maxima and curvilinear ramps are most evident with low refractive errors. The half-height widths of the point- and line-spread functions change little. The optical transfer function is reduced in proportion to the distribution of light between the image components. CONCLUSIONS: Stable point and line half-height widths explain why Snellen visual acuity is insensitive to annular blur. Contrast sensitivity correlates with symptoms of haze and fog. Halos and ghost images are associated with secondary optical maxima and curvilinear ramps. Neither visual acuity nor contrast sensitivity can predict halos or ghost images. Halos and ghost images will be most prevalent in low illumination and for low refractive corrections. High refractive errors will produce fewer visual side effects than low refractive errors. PMID- 1450117 TI - Silicon cast method for quantification of photoablation. AB - BACKGROUND: Topometry and measurement of photoablation patterns are key questions for keratorefractive photoablation. Ablation rates have been determined previously by either tissue perforation or by micrometry performed on histologic sections. METHODS: A three-dimensional cast of cornea after irradiation was made by using a two-component silicon gel that polymerizes within minutes, thus preserving the corneal topography immediately after photoablation. Polymerization is athermal and nontoxic. The resulting silicon blocks were cut perpendicularly to the anterior surface and measured by calibrated light microscopy. RESULTS: The silicon surface is extremely smooth and the accuracy of the cast is better than 0.25 micron. Reproducibility and long-term stability were demonstrated for casts of photoablated polymethylmethacrylate. Thus, ablation rates and profile, volumetry, and topometry can be determined following laser ablation. The method has been applied for 193-nanometer excimer laser in vitro irradiation of the human cornea. Ablation rates in Bowman's layer and stroma for various radiant energies and distinct pulse numbers were found to be in agreement with published data, and an incubation effect for the first laser pulses could be demonstrated. CONCLUSIONS: The method is nondestructive, accurate, inexpensive, practical, and reduces requirements for laboratory animals. PMID- 1450118 TI - A comparison of excimer laser (308 nm) ablation of the human lens nucleus in air and saline with a fiber optic delivery system. AB - BACKGROUND: Photoablation with excimer lasers has demonstrated precise tissue cutting and minimal thermal damage. Potential ophthalmic applications of these lasers include remodelling of the corneal surface, glaucoma treatment, and phacoablation. Ablation of human lens with a 308 nm XeCl excimer laser light delivered through a fiber has been demonstrated in preliminary experiments. Intraocular delivery of laser light must be done in a fluid medium to preserve the integrity of ocular structures. However, little information is available on the effect of the fluid media on the ablation process. Therefore, a series of experiments was conducted to determine whether the ablation of human lens nucleus at 308 nm via a fiber differs in air and saline media. METHODS: Ablation of human lens nuclei (n = 30) was conducted with a XeCI excimer laser (308 nm) coupled to a 600 microns core size fiber. Irradiation was performed at 2.8 mJ/cm2 energy density and 20 Hz. The fiberoptic was brought to contact with the lens nucleus and remained fixed for the duration of irradiation. Variables consisted of the medium (air or saline) and number of pulses delivered (100 to 10,000). Following establishment of the tissue shrinkage ratio, the depth of each crater and the tissue volume removed were measured histologically. The histological features of nucleus ablation in air and in saline were also examined with both light and scanning electron microscopy. RESULTS: Light microscopy revealed that the average zone of thermal damage adjacent to the crater is thinner in the presence of saline (60 microns, SD = 6 microns) than it is in air (90 microns, SD = 12 microns). In both media, the thickness of the zone of thermal damage is greater at the surface than it is at its base. Following irradiation in air, deep sharpedged craters with smooth walls are formed. Craters formed by irradiation in saline are characterized by reduced depth and irregular walls. For the same number of pulses applied (500, 1000, and 2000), the mean depth of ablation per pulse in air (8.6 to 2.7 microns/pulse) was greater by approximately a factor of two than that in saline (4.10 to 1.30 microns/pulse) at P < .01. However, the mean ablated volume removed per pulse was greater in saline (0.00250 to 0.00150 mm3/pulse) than in air (0.00120 to 0.00080 mm3/pulse), for the same number of pulses (1000, 2000) at P < .01. CONCLUSIONS: In comparing the data for the same number of pulses applied in air and in saline, it appears that the depth of crater formed by irradiation in air is deeper than that in fluid. The overall volume ablated is greater in fluid than it is in air at 1000 and 2000 pulses. Additionally, the zone of thermal damage is thinner in the presence of saline than it is in air. Smoother crater shapes were observed following irradiation in air than in saline. These results suggest that under this specific experimental setup, the ablation in saline is different from that in air. PMID- 1450119 TI - Pneumococcal infection after temporary tarsorrhaphy for epikeratophakia. PMID- 1450120 TI - Corneal wound healing after excimer laser ablation in rabbits: expanding versus contracting apertures. AB - BACKGROUND: Photorefractive keratectomy for myopia can be performed using an expanding or contracting iris diaphragm, either of which allows for greater ablation centrally and less tissue ablation toward the edge of the treatment zone. METHODS: To compare the effects of these two strategies, eight rabbits underwent bilateral 5.00-diopter myopic ablations, performed with a contracting diaphragm in one eye and an expanding diaphragm in the other. RESULTS: The rate of epithelial healing and degree of anterior stromal haze, monitored by a masked observer, were similar for the two groups, as was the amount of corneal flattening. CONCLUSIONS: These results in rabbit corneas do not suggest a particular advantage of either the expanding or contracting apertures for achieving central corneal flattening in photorefractive keratectomy. PMID- 1450121 TI - Modified surgical technique for repeated epikeratophakia surgery in aphakic eyes. AB - BACKGROUND: Incomplete epithelial removal from the peripheral keratectomy at the time of repeat epikeratophakia surgery can lead to interface downgrowth and consequent failure, as observed in the case reported herein. We present a modification of the standard surgical technique aimed at avoiding such complication. METHODS: A 69-year-old white female underwent a third aphakic epikeratophakia modified to reduce the risk of epithelial interface downgrowth, which had caused a previous failure. The aphakic tissue lens, 8.5 mm in diameter, was sutured into a corneal pocket obtained at a deeper level, inside the peripheral keratectomy used for the previous two procedures. RESULTS: Useful visual acuity (20/60) was obtained and the refractive outcome remained stable up to 1 year postoperatively. Epithelial interface downgrowth did not recur. CONCLUSIONS: Despite the possible risk of perforation while undermining the recipient cornea at a deeper level, the modified technique might offer a more effective method of preventing epithelial downgrowth after repeat epikeratophakia surgery. PMID- 1450122 TI - Facilitation of ab interno radial keratotomy by air keratoplasty. AB - BACKGROUND: Ab interno radial keratotomy is a keratorefractive procedure with radial incisions made by externalizing a blade inserted in the deep stroma. A major limitation of the procedure is the technical inability to establish a safe pre-Descemetic stromal entry of the blade with subsequent suboptimal depth of the radial incisions. A technique to delineate Descemet's membrane was investigated to obtain deeper incisions with the ab interno radial keratotomy. METHODS: Air was injected with a 30-gauge needle mounted on a 3-milliliter syringe and entering the deep stroma at the limbus in human donor eyes. The injection was done in a pulse fashion with the needle tip advanced 3 mm away from the limbus. Ab interno radial keratotomy was then performed with and without air injection. RESULTS: Bubbles were localized to the pre-Descemet region. The depth of the radial keratotomy incisions increased from 57.7% (SD = 11.5%) without air injection, to 83.0% (SD = 10.6%) with air injection. CONCLUSIONS: Deep stromal air injection delineates the pre-Descemet space, allowing deeper radial incisions with the ab interno radial keratotomy. PMID- 1450123 TI - Surgical correction of hyperopia: a new experimental approach using X-incision and suture technique in rabbits. AB - BACKGROUND: A new experimental surgical technique to correct hyperopia by steepening the central corneal curvature was performed on the eyes of rabbits. METHODS: After X-shaped incisions at four quadrants of the paracentral cornea, four deep, transverse interrupted sutures were placed across the incisions and the knots were tightened to compress the corneal tissue in the direction of the suture. Twenty-three eyes of 12 albino rabbits were divided into group A (7 eyes) with a 4-millimeter diameter clear zone, group B (9 eyes) with a 6-millimeter diameter clear zone, and control group C, consisting of 7 contralateral eyes of group A without any incision or suture. RESULTS: There was significant (p < .01) steepening of the central cornea as measured by the keratometer at postoperative 8 weeks in group A (+1.88 diopters) and group B (+1.68 D) compared with that of the control group C (-3.44 D). The difference in effect of hyperopic correction between groups of A and B was not statistically significant. CONCLUSIONS: This procedure serves only as an experimental model of corneal response to incisions and sutures and is not for use in human corneas. PMID- 1450124 TI - Sliding flap of conjunctival limbus to prevent recurrence of pterygium. AB - BACKGROUND: Several techniques have been advocated for the excision of a pterygium: bare sclera, conjunctival flaps, free conjunctival graft, and labial mucous membrane graft. METHODS: Twenty eyes were treated with a sliding flap of limbal conjunctiva into the scleral bed of the excised pterygium, using 7-0 and 8 0 Vicryl sutures. Corticosteroids and tear substitutes were administered postoperatively. RESULTS: There was one recurrence in the 20 eyes performed with 1 year follow up. CONCLUSIONS: Recurrence was limited to that of 5% (1 case out of 20). Postoperative inflammatory reaction was minimal. PMID- 1450125 TI - A granny-style slip knot for use in eye surgery. AB - An adjustable knot for use in ocular surgery is described herein. The first part of the knot is a granny knot, which allows tension to be adjusted. The advantages of this knot are: 1) ease of tying; 2) adjustability; and 3) small size of the knot. PMID- 1450126 TI - Intrastromal photorefractive keratectomy with a new optically coupled laser probe. AB - BACKGROUND: Intrastromal photorefractive keratectomy is a new procedure in which compact linear or area regions of the corneal stroma can be vacuolized, yielding changes in corneal curvature. METHODS: Diffraction-limited 1064-nanometer light pulses from a high rep rate Q-switched Nd-YAG laser were coupled through novel means into a probe with index-matched optical contact with the cornea. The resulting extremely reduced focal region initiated a plasma point that was free of shock front effects where tissue was reduced to liquid. This probe process was applied to the corneas of eye-bank eyes, and to living rabbit and primate eyes. The refractive effects were evaluated with slit-lamp microscopy, keratoscopy light and electron microscopy. RESULTS: Refractive effects similar to refractive keratotomy were observed immediately after treatment. Intrastromal highly localized vacuolized regions were observed at the depth of focus with variability of only 20 microns. The plasma point vacuoles were about 100 microns in diameter. Stromal material that occupied the vacuole space appeared completely reduced to liquid. The transition region between vacuole and normal tissue was less than 0.5 microns. The treatment vacuoles disappeared to the unaided eye 24 to 48 hours after treatment. CONCLUSIONS: Corneal refractive power can be achieved with intrastromal keratectomy. PMID- 1450127 TI - Keratoconus, videokeratography, and refractive surgery. PMID- 1450128 TI - Critique of hexagonal keratotomy raises a ruckus. PMID- 1450129 TI - Critique of hexagonal keratotomy raises a ruckus. PMID- 1450130 TI - Contact lenses in pregnancy. PMID- 1450131 TI - Antenatal HIV testing. PMID- 1450132 TI - The variability of urinary protein and creatinine excretion in patients with gestational proteinuric hypertension. AB - OBJECTIVE: To determine the variability of protein excretion in patients with proteinuric hypertension and the accuracy of either a urinary protein/creatinine ratio or a Multistix examination for the estimation of a 24 h protein excretion. DESIGN: An indwelling urinary catheter was placed for 24 h and successive 8 h specimens examined. SETTING: A tertiary referral hospital in Cape Town, South Africa. SUBJECTS: 22 women with significant proteinuria in pregnancy were studied. MAIN OUTCOME MEASURES: The urine volume, protein excretion and creatinine excretion in eight hourly periods were measured. Multistix examination of each specimen was recorded. RESULTS: A large coefficient of variation in urine volume (41%), amount of protein excreted (44%) and the amount of creatinine excreted (22%) in the eight hourly specimens were noted. The protein creatinine ratio did not accurately predict the 24 h protein excretion. The Multistix examination was less accurate with increasing amounts of proteinuria. The amount of creatinine excreted correlated with the volume of urine passed (r = 0.43). CONCLUSION: The analysis of a 24 h specimen or urine for protein excretion remains the best method of monitoring proteinuria in pregnancy. The amount of creatinine excreted in 24 h cannot be used as an index of completeness of collection of the 24 h specimen. PMID- 1450133 TI - Prepregnancy counselling: experience from 1,075 cases. AB - OBJECTIVE: To assess the activity of a prepregnancy counselling clinic in terms of investigations, counselling, treatment and subsequent pregnancy outcome. DESIGN: Review of 1,075 couples attending over a nine year period. SETTING: University Hospital offering a tertiary referral service for fetal medicine. SUBJECTS: Couples referred to the clinic from a variety of sources. MAIN OUTCOME MEASURES: Categories of referral, value of diagnostic tests, and subsequent pregnancy outcome. RESULTS: The main categories of referral were: previous miscarriage (44.4%); previous fetal abnormality (19.6%); chronic maternal disease (22.3%); and others (13.7%). Routine investigations produced a low yield of abnormality (1%), in contrast to investigations selected for specific reasons (12%). Subsequent pregnancy outcome, which was unaltered in either the previous miscarriage or fetal abnormality groups, did improve in the chronic maternal disease group. CONCLUSIONS: This study does not prove the value of prepregnancy counselling. However, it does illustrate the importance of making an accurate assessment of previous problems and current health as a means of determining both maternal and fetal risks in a subsequent pregnancy, a process which seems to lead to an improved outcome within selected groups. The importance of continuity of care in all couples, especially when there has been a previous adverse pregnancy outcome is emphasized. PMID- 1450135 TI - The efficacy of phenytoin in relation to serum levels in severe pre-eclampsia and eclampsia. AB - OBJECTIVES: To investigate the efficacy of phenytoin in relation to total and free serum levels in patients with severe pre-eclampsia and eclampsia. DESIGN: Prospective descriptive study. SETTING: Labour Ward, King Edward VIII Hospital, Durban, South Africa. Tertiary referral centre serving an underprivileged community. SUBJECTS: Eleven patients admitted with a hypertensive crisis. Four patients had eclampsia and 7 had impending eclampsia. MAIN OUTCOME MEASURES: Free and total phenytoin levels; efficacy of phenytoin as an anticonvulsant and side effects of therapy. RESULTS: Although total phenytoin levels were within the therapeutic range, free phenytoin levels were abnormally high in all patients. Three patients (2 with eclampsia and 1 with imminent eclampsia) each had a seizure after phenytoin treatment had been initiated. CONCLUSION: Neither total nor free phenytoin levels were good predictors of seizure control. It is postulated that the poor performance of phenytoin as an anticonvulsant in severe eclampsia may relate to inadequate distribution of the drug to the brain as a result of cerebral oedema and poor cerebral perfusion rather than paradoxical seizure activity associated with high free phenytoin levels. PMID- 1450134 TI - The effect of pH on release of PGE2 from vaginal and endocervical preparations for induction of labour: an in-vitro study. AB - OBJECTIVE: To study the effect of pH and precoating with obstetric cream on the release of prostaglandin E2 (PGE2) from commercially available triacetin and starch based gels, lactose based vaginal tablets and sustained release hydrogel polymer pessaries in-vitro. DESIGN: A prospective observational study. METHODS: PGE2 preparations held in dialysis bags were placed in Ringers lactate buffer and release of PGE2 into the buffer was measured over 8-12 h by radioimmunoassay. The hydrogel polymer pessary was also assessed after precoating with obstetric cream. MAIN OUTCOME MEASURES: In-vitro PGE2 release at pH 7.4, pH 5.4 and pH 3.4. RESULTS The gel preparations provided rapid and reliable release, while the lactose based vaginal tablet provided much lower release of PGE2 with sudden and variable release occurring after 5-8 h, an effect which was enhanced at low pH. With the triacetin gel preparation, release of PGE2 was reduced at lower pH, while the starch based gel appeared to provide optimal release at pH 5.4. The hydrogel polymer pessaries provided linear release in-vitro and this was reduced at pH 3.4. In addition, precoating the sustained release hydrogel polymer pessaries with obstetric cream virtually abolished release of PGE2. CONCLUSIONS: As the vagina is normally acid, these results suggest that vaginal pH could influence PGE2 release and this may result in variable clinical responses. In view of this, pH should be taken into account in the development of preparations for clinical use. Furthermore, the use of obstetric cream should be avoided when administering PGE2 preparations for induction of labour. PMID- 1450136 TI - Spontaneous resolution of pre-eclampsia-related thrombocytopenia. AB - OBJECTIVE: To observe the spontaneous resolution of pre-eclampsia-related thrombocytopenia. DESIGN: A retrospective study. SETTING: High Risk Pregnancy Unit, John Radcliffe Maternity Hospital, Oxford. SUBJECTS: Thirty women with pre eclampsia complicated by the HELLP/ELLP syndrome who did not receive any specific treatment for their thrombocytopenia. INTERVENTION: Serial platelet counts throughout labour and the puerperium until the platelet counts returned to levels above 100 x 10(9)/l. MAIN OUTCOME MEASURES: Time taken from delivery and platelet nadir for platelet counts to return to levels above 100 x 10(9)/l. The rate of recovery from the platelet nadir was measured by the slope of the serial platelet counts plotted against time. RESULTS: The mean time until platelet count exceeded 100 x 10(9)/l was 67 h (SD 25) after delivery and 44 h (SD 17) from the platelet nadir. All women had counts above 100 x 10(9)/l by 111 h after delivery, and by 88 h after the platelet nadir. Although the time to recovery appeared to depend on the degree of thrombocytopenia, the rate of resolution did not. CONCLUSION: These data can be used as a guide by clinicians as to the expected time course for postpartum resolution of pre-eclampsia-related thrombocytopenia. PMID- 1450137 TI - Pre-eclampsia and trisomy 13. AB - OBJECTIVE: To assess the reported association between field trisomy 13 and maternal pre-eclampsia. DESIGN: A retrospective case-control study. SUBJECTS: Twenty-five women who gave birth to trisomy 13 infants in southwest England between 1971 and 1989; 38 women who gave birth to trisomy 18 infants in the same region over the same time and 50 women with normal karyotype infants matched for age, parity, and date of delivery with the trisomy 13 group. MAIN OUTCOME MEASURES: The medical records of all the women in the three groups were analysed for evidence of pre-eclampsia. Four different thresholds of pre-eclampsia were used. The incidence of pre-eclampsia was compared between the three study groups and analysed separately for primigravid and multigravid women. RESULTS: The incidence of pre-eclampsia in pregnancies complicated by trisomy 13 was significantly higher than the incidence in the trisomy 18 and the normal karyotype control groups. This association was more pronounced in primigravid pregnancies. CONCLUSIONS: This, the largest survey of trisomy 13 and pre eclampsia to date, suggests an association between the two conditions. It also supports the argument for a fetal factor in the pathogenesis of pre-eclampsia. We speculate on how genes encoded on chromosome 13 may be responsible. PMID- 1450138 TI - Transfer and metabolism of platelet-activating factor by fetal membranes, amnion and chorio-decidua. AB - OBJECTIVE: To determine the metabolism of 3H-Platelet-activating factor (3H-PAF) during transfer through human fetal membranes. DESIGN: 3H-PAF was added to the fetal side of cultured intact fetal membranes, amnion and chorio-decidua obtained from three pregnancies ending in elective caesarean section. MAIN OUTCOME MEASURES: Radioactivity was measured on both sides of the tissue, and in the tissue itself. In some experiments, the metabolism of 3H-PAF was assessed by thin layer chromatography. RESULTS: Very little 3H-PAF crossed the intact fetal membrane (< 2%) during 24 h of culture. Most of the 3H-PAF which accumulated in the membrane was converted to a range of metabolites in the chorio-decidua. CONCLUSIONS: These results suggest that PAF in amniotic fluid may not reach the decidua, and therefore is unlikely to be involved in the control of prostaglandin production from this tissue. PMID- 1450139 TI - The importance of serial biophysical assessment of fetal wellbeing in gastroschisis. AB - OBJECTIVE: To review antenatal and intrapartum assessment of pregnancies complicated by gastroschisis. DESIGN: Retrospective descriptive study. SETTING: University College Hospital, London. SUBJECTS: 24 consecutive cases of gastroschisis between 1986 and 1991. RESULTS: The gestational age at sonographic diagnosis was 20.3 weeks (SD 6.77) and at birth was 36.5 weeks (SD 2.06). There were 21 live births, all with good surgical outcome. There were 16 vaginal deliveries and eight caesarean sections. The elective sections were for oligohydramnios and dilated bowel (1) and clinically suspected growth retardation (1); the intrapartum caesarean sections were for fetal distress (4) and premature breech presentation (2). There were six with dilated gut on ultrasound; one of these ended in a stillbirth. There was a significant association between gut dilatation and caesarean section for fetal distress (P = 0.004). There was also a significant association between meconium staining and fetal distress (P = 0.021). Of these babies, 46% were < or = third centile for corrected birth weight. CONCLUSIONS: While half of the babies with gastroschisis were small for gestational age at birth, reliable antenatal prediction of birth weight is difficult. Gut dilatation may be an indicator of either antenatal or intrapartum fetal distress, but does not correlate with poor neonatal surgical outcome. We suggest close antenatal surveillance of fetal wellbeing in all cases of gastroschisis because, in addition to growth retardation, many show some evidence of fetal distress and 12.5% end in stillbirth, even when appropriately grown. PMID- 1450140 TI - The prognostic value of fetal ultrasonography before induction of labour. AB - OBJECTIVE: To investigate whether ultrasound examination of the fetus and amniotic fluid before induction of labour can provide useful prognostic information about the course of labour and mode of delivery. DESIGN: A prospective observational study. SETTING: The delivery suite of St Mary's Hospital, London. SUBJECTS: 101 women undergoing induction of labour. MEASURED VARIABLES: Biparietal diameter, head circumference, abdominal circumference, occipital position, amniotic fluid volume and umbilical artery Doppler velocimetry waveforms. MAIN OUTCOME MEASURES: The outcome of labour was assessed in terms of the induction delivery interval, the mode of delivery and the incidence of abnormal cardiotocograms in labour. RESULTS: Seven women were delivered by emergency caesarean section early in the first stage of labour because of a significant abnormality of the fetal heart trace and these pregnancies were characterized by small fetal abdominal circumference measurements. Marked oligohydramnios was also noted in five of these seven subjects. Small or average size babies who were surrounded by an adequate volume of amniotic fluid tended to be born spontaneously, whereas the majority of operative deliveries for failure to progress in labour were associated with fetal abdominal circumference measurements > or = 340 mm. The mean Bishop score of women before labour who delivered spontaneously was not significantly different from the scores of women who had a forceps delivery or caesarean section. Abnormal cord Doppler waveforms were observed in only one instance. CONCLUSIONS: In women undergoing induction of labour, the measurement by ultrasonography of two variables (fetal abdominal circumference and amniotic fluid volume) may allow the prospective identification of pregnancies at increased risk of fetal distress or dystocia. If these findings can be replicated in early spontaneous labour than more rational utilization of resources may be possible in hospital based obstetric practice. PMID- 1450141 TI - Long term follow up of women after hysterectomy with a history of pre-invasive cancer of the cervix. AB - OBJECTIVE: A long term review of women after hysterectomy with a history of pre invasive carcinoma of the cervix. DESIGN: 193 women had cervical intra-epithelial neoplasia and two had adenocarcinoma in situ either at hysterectomy or at previous cone biopsy. These were followed up by annual cytology. SETTING: South Glamorgan Health Authority. SUBJECTS: Of 195 women who had a hysterectomy, 143 have been followed up cytologically for more than 10 years and 43 for more than 20 years: a total of 2800 women years of experience. MAIN OUTCOME MEASURES: Timing of abnormal smears. RESULTS: A detailed review of the five women with abnormal smears. The estimated percentage of women who remain negative is 98% at five years, 98.4%, at 10 years and 96.5% at 20 years. CONCLUSION: Cytological screening of all women who had a hysterectomy with a history of CIN is indicated for the first two years after hysterectomy. Thereafter the estimated incidence of 0.7 per 1000 women years is higher than the general population but it is not a sufficient reason to screen more frequently. We recommend screening for the carcinoma of the vagina to be every three years which is the same screening frequency as for cervical carcinoma in the general population. PMID- 1450142 TI - Transcervical resection of the endometrium: a review of 400 consecutive patients. AB - OBJECTIVE: To assess the efficacy of transcervical resection of the endometrium (TCRE) in women presenting with menstrual disorders. DESIGN: A retrospective audit of 400 patients. SETTING: The Department of Gynaecology, St John's Hospital, Chelmsford, Essex. SUBJECTS: 400 consecutive referrals with various bleeding disorders which were suitable for treatment with TCRE. INTERVENTIONS: TCRE, either partially or completely. MAIN OUTCOME MEASURES: Patient satisfaction with procedure at 4 months. The procedure was initially recorded as a failure if any further therapy was required but satisfaction after a second procedure was assessed. RESULTS: 432 procedures were performed in 400 women. Major operative complications were rare with two (0.46%) uterine perforations, four (0.93%) primary haemorrhages requiring Tamponade to control bleeding and one (0.23%) secondary haemorrhage requiring hysterectomy to control it. Glycine toxicity was not clinically apparent. 85% were satisfied after the initial TCRE and 92% were satisfied if the procedure was repeated. CONCLUSION: TCRE is an advance in the management of menstrual disorders. Extensive training is required to minimise complications. The lack of long term follow-up is its major deficiency but this will be rectified in the future. PMID- 1450144 TI - Recurrent miscarriage, cystic hygroma and incontinentia pigmenti. PMID- 1450143 TI - Randomised comparative study in 217 women of three disposable plastic IUCD thread retrievers. AB - OBJECTIVE: To assess the relative efficacy of three disposable plastic instruments in the retrieval of 'missing' IUCD threads. DESIGN: A prospective randomised comparative single centre study. SETTING: Family Planning Clinic in London, UK. SUBJECTS: 217 of 350 IUCD users referred to the research team with 'missing' IUCD threads entered the study. INTERVENTION: All women initially underwent exploration of the endocervical canal with Spencer Wells forceps. When this procedure did not retrieve the threads, the patients were entered into the study. A maximum of two randomly chosen plastic IUCD thread retrievers were then used in any one patient to explore the uterine cavity and capture the 'missing' threads. The order in which the two retrievers were employed was also determined at random. Four separate entries into the uterine cavity were permitted with each instrument, the endocervical canal being explored with Spencer Wells forceps after each retraction of the instrument to identify the possible descent of the threads. MAIN OUTCOME MEASURES: Threads brought down beyond the external cervical os, or threads brought to within the endocervical canal and then grasped by Spencer Wells forceps. RESULTS: In approximately 40% of all patients, the threads were retrieved with Spencer Wells forceps alone and a further 40% with the disposable plastic retrievers. About 5% had no retrievable threads, and only 2.5% of the referred patients required general anaesthesia for removal of their IUCD. The analysis of the comparative trial was confined to the 197 patients with retrievable threads which could not be brought below the external os with Spencer Wells forceps. The first plastic retriever used was successful in 50% of patients. The Retrievette (59%) and the Emmett (53%) performed better than the Mi Mark Helix (37%) in this study. The difference was statistically significant (P = 0.03) and the 95% confidence interval for the difference of the Mi-Mark Helix from the other two retrievers was 4% to 33%. This retrieval rate for the Mi-Mark Helix was much worse than in previously reported studies, though one doctor did have a better success rate with this retriever. The success rates, using a second plastic retriever randomly chosen from the two not used in the first attempt, were almost identical to those observed with the first retrievers: 63%, 56% and 36%. The success rate did not appear to be influenced by the length of thread, day of cycle, device type or parity. The success of the second retriever tried did not seem to be influenced by the retriever that had failed previously. CONCLUSIONS: Based on our experience, the initial exploration of the endocervical canal with Spencer Wells forceps is invaluable. If this simple manoeuvre fails to retrieve the 'missing' threads, either the Retrievette or the Emmett thread retrievers are useful tools in general practice or in the family planning clinic setting. PMID- 1450145 TI - Lacking anastomoses between left and right uterine arteries in uterus bicornis during pregnancy as demonstrated by Doppler velocimetry. PMID- 1450146 TI - Polycythemia associated with leiomyoma of the uterus. PMID- 1450147 TI - Aggressive angiomyxoma of the female pelvis and perineum. Report of two cases and review of the literature. PMID- 1450148 TI - Necrotising granulomatous endometritis following endometrial ablation therapy. PMID- 1450149 TI - Under-reporting of medical terminations of pregnancy. PMID- 1450150 TI - Transvaginal versus transrectal sonography in postmenopausal women. PMID- 1450151 TI - Cervical cone biopsy: a report of one hundred consecutive operations performed as day cases. PMID- 1450152 TI - Incarceration of a bicornuate retroverted gravid uterus presenting with bilateral uretric obstruction. PMID- 1450154 TI - Which hormone tests for the diagnosis of polycystic ovary syndrome. PMID- 1450153 TI - Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean. PMID- 1450155 TI - Audit matters. PMID- 1450156 TI - Treatment of oral cancer by interstitial irradiation using iridium-192. AB - Sixty-seven patients with squamous cell carcinoma of the oral cavity were treated by implantation of radio-active iridium wire between 1977 and 1986. The results are presented in the hope of providing a comparison with those of primary surgical management. The crude 5-year survival rates were 61% for T1, 74% for T2, and 37% for T3 tumours. The major causes of death were uncontrolled tumour in the neck and intercurrent disease. Seven of 52 patients with T1 or T2 tumours (13%) developed local recurrence at the primary site; five were salvaged surgically, for an ultimate failure rate of 4%. The ultimate failure for a group of 15 T3 tumours was 47%. The only morbidity was a 31% incidence of soft tissue ulcers occurring during the first 18 months after treatment, none of which persisted. Elective external beam radiotherapy to the clinically negative neck significantly reduced the incidence of overt lymph node metastases. PMID- 1450157 TI - Prevalence of post-traumatic stress disorder in patients with chronic idiopathic facial pain. AB - 34 patients with chronic idiopathic orofacial pain were assessed by a structured clinical interview for diagnosis of mental disorders according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-III-R). Five (15%) had a history of post traumatic stress disorder (PTSD) which coincided with the pain onset. The majority of these PTSD sufferers also had a personality disorder. The implications of these findings in the diagnosis and management of post-traumatic chronic TMJ pain syndromes is discussed. PMID- 1450158 TI - Waiting list hurdles and the role of the pre-surgical booking clinic. AB - Patients requiring surgery have two main hurdles to cross--long waiting lists and the risk of late cancellation when dates become available. A study was conducted to investigate the inconvenience caused by late cancellation, and to show how the pre-surgical assessment clinic can be utilised to reduce the dissatisfaction and disappointment of the current waiting list system in surgery. PMID- 1450159 TI - Le Fort I maxillary osteotomy: is it possible to accurately produce planned pre operative movements? AB - The planned preoperative maxillary movements for five groups of patients requiring orthognathic surgery were prospectively compared to the actual surgical movements achieved in the operating theatre. There was a very poor success rate in achieving predicted movements in all the patient groups. There is a need to test and implement a reliable method of assisting the surgeon in spatially orientating the jaws on the operating table. PMID- 1450160 TI - Experience with ITI osseointegrated implants at five centres in the UK. AB - Experience with the two-part ITI titanium implant system at five centres in the UK is reported. A total of 461 implants were inserted in 176 patients, who received 189 prostheses. Criteria for the assessment of success following implantation are listed. Results over a 3-year period showed a success rate of 94% when implants were used for mandibular overdentures and crown and bridge prosthetics. A lower success rate in the edentulous maxilla was recorded. PMID- 1450161 TI - Abnormal bone masses in Klippel-Feil syndrome. AB - Five female patients with Klippel-Feil syndrome (KFS) are presented with abnormal bony masses in the mandibular ramus region. The features of KFS are described with assessment and treatment of the five patients. Although congenital duplication of mandibular rami in KFS has been previously documented, we believe this is the first series of patients with this deformity. PMID- 1450162 TI - Equipment and methods for simple sensory testing. AB - Four simple tests which can be used for routine sensory testing following trigeminal nerve injuries are suggested. The methods for constructing the equipment needed for these tests are described. PMID- 1450163 TI - The origin of the temporalis muscle flap. AB - This paper explores the origin of the temporalis muscle flap which has been attributed to Golovine, a Moscow ophthalmic surgeon, who described a forehead skin transposition flap. Small temporalis muscle transpositions were used in surgery for TMJ ankylosis, but the use of the majority of the muscle for reconstruction of facial defects was first described by Sir Harold Gillies during the 1914-18 war. PMID- 1450164 TI - Fine needle aspiration cytology in the diagnosis of amyloid in the submandibular gland. PMID- 1450165 TI - Traumatic cavernous carotid aneurysm resulting in blindness. AB - A case of traumatic aneurysms of the cavernous internal carotid artery which resulted in blindness is presented. This condition would appear to be a rare consequence of maxillofacial trauma, although fistulae are relatively common. The reasons for this apparent paradox, the difficulty of diagnosis and the management are discussed. PMID- 1450166 TI - Dermatofibrosarcoma protuberans of the scalp. AB - Dermatofibrosarcoma protuberans is an uncommon tumour of the dermis and rarely occurs on the scalp; there are few known predisposing factors. A case is described of such a tumour that occurred at the site of radiotherapy for a basal cell carcinoma. Histological characteristics, behaviour and management of dermatofibrosarcoma protuberans are discussed. PMID- 1450167 TI - Oral cancer--time for some home truths? PMID- 1450168 TI - Intercollegiate assessment in oral and maxillofacial surgery. PMID- 1450169 TI - Lipoprotein profile of a Greenland Inuit population. Influence of anthropometric variables, Apo E and A4 polymorphism, and lifestyle. AB - Previously it has been reported that Greenland Inuit (Eskimos) from the Uummannaq district display low levels of plasma cholesterol and triglycerides and relatively high levels of high density lipoprotein (HDL) when compared with healthy Danish control subjects (Lancet 1971;1:1143-1146). Here we present data obtained in 1989 that show the following. In a group of 133 healthy adult Greenland Inuit from Nanortalik, the levels of plasma cholesterol and low density lipoprotein (LDL) cholesterol (6.39 and 4.39 mmol/l, respectively) were slightly higher than "normal" values found in western societies, whereas the HDL cholesterol level was markedly higher (1.64 mmol/l). Compared with most Caucasian populations, the Inuit population we studied exhibits a high apolipoprotein (APO)E*4 allele frequency (0.229), whereas the APOE*2 allele frequency was extremely low (0.015). In contrast to Caucasian populations, in the Inuit population the apoE polymorphism showed only a minor influence on the plasma lipid and (apo)lipoprotein levels, as evaluated by multiple regression analysis, with the exception of apoE levels. This absence of an effect could be explained by the low very low density lipoprotein (VLDL) plus intermediate density lipoprotein (IDL) cholesterol levels. The contributions of eicosapentaenoic acid and linoleic acid to the total amount of fatty acids in plasma cholesterol esters differed markedly from those reported in 1971 for another Greenland Inuit population (3.2% versus 15.8% and 49.5% versus 20.4%, respectively), thereby resembling values now found in the average western population. Even in those Inuit who reported exclusive consumption of the traditional Inuit diet (13% of the population), the fatty acid composition of the plasma cholesterol esters closely resembled the values measured in western populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450170 TI - Chronic rejection of rat aortic allografts. III. Synthesis of major eicosanoids by vascular wall components and effect of inhibition of the thromboxane cascade. AB - We have previously demonstrated that rat aortic allografts from the DA (RT1a) to the WF (RT1v) strain develop chronic arteriosclerotic changes in the vascular wall after a short spontaneously reversible acute rejection episode. These changes, which are lacking in syngeneic DA-to-DA control grafts, are virtually identical with those observed in human allografts during chronic rejection. In this study we have investigated whether eicosanoids are involved in the generation of arteriosclerotic changes. Incubation of aortic wall rings in vitro and immunochemical assays demonstrated that the arteriosclerotic allografts synthesize significantly more thromboxane B2 (TxB2) but not 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) or leukotriene B4. The increased synthesis of TxB2 in the allografts persisted for at least 5 months after transplantation. Separate incubation of the two major components of the vascular wall, after microdissection of the intima and (media plus) adventitia, demonstrated that most of the synthesis of TxB2 during chronic rejection was due to the outer layer of aorta, presumably the inflammatory cells of the adventitia. In contrast, most of the 6-keto-PGF1 alpha was synthesized by the inner layer of the aorta, presumably the endothelial cells and the smooth muscle cells of the intima. Administration of 1 mg.kg-1 x day-1 of a specific TxA2 receptor inhibitor, GR32191B, to the recipient rat reduced the proliferative response of inflammatory cells in the adventitia by 30%, as detected by in vivo tritiated-thymidine (3H-TdR) labeling and autoradiography, but did not reduce the proliferative response of smooth muscle cells in the media and intima.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450171 TI - Upper-body fat distribution: a hyperinsulinemia-independent predictor of coronary heart disease mortality. The Paris Prospective Study. AB - The Paris Prospective Study is a long-term investigation of the factors predicting coronary heart disease in a large population of middle-aged men. The first follow-up examination involved 7,152 subjects, who were natives of metropolitan France and were free of any cardiovascular history. At that time, the usual cardiovascular risk factors and plasma insulin levels were recorded. An index of body fat distribution, the iliac-to-thigh ratio, was entered into the list of predictive variables, despite the fact that it had been measured 1 year before the first follow-up examination. After 11 years of mean follow-up, 129 of the men had died of coronary heart disease. Univariate analysis showed that the iliac-to-thigh ratio (p < 0.0001) and plasma insulin level (both fasting [p < 0.003] and 2-hour postload [p < 0.02]), as well as the four major risk factors of coronary heart disease (age, smoking, blood pressure, and plasma cholesterol level) were significantly higher in subjects who died of coronary heart disease compared with those who had died of another cause or were alive at the end of follow-up. In multivariate stepwise logistic regression, the iliac-to-thigh ratio appeared as an independent predictor of coronary heart disease death, thereby causing the removal of fasting insulin level from the list of significant independent predictors. Nevertheless, in a model that entered 2-hour postload insulin in two classes (high or low), both the insulin level and iliac-to-thigh ratio were found as significant independent predictors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450172 TI - Mitogenic activity of interferon gamma on growth-arrested human vascular smooth muscle cells. AB - Interferon gamma (IFN-gamma) is a multifunctional lymphokine secreted by activated T lymphocytes, which are found in atherosclerotic lesions. IFN-gamma has been reported to suppress the proliferation of vascular smooth muscle cells (SMCs). However, as we report in this paper, IFN-gamma is mitogenic for vascular SMCs under certain circumstances. Recombinant human IFN-gamma (1-100 units/ml), in a dose-dependent fashion, stimulated cell multiplication and [3H]thymidine and 5-bromo-2'-deoxyuridine incorporation into DNA by cultured arterial SMCs that had been growth arrested by culturing in 1% plasma-derived serum for 5 days. IFN gamma also accentuated the mitogenic activity of platelet-derived growth factor (PDGF)-BB. A time-course study revealed that there was a time lag of 4-6 hours between the G1-->S transition of quiescent SMCs stimulated by IFN-gamma and that of SMCs stimulated by PDGF-BB. A synergistic effect of IFN-gamma on the mitogenicity of PDGF became apparent after a similar time lag, suggesting that the IFN-gamma-related mitogenicity is mediated by a substance(s) secreted by IFN gamma-treated SMCs. In fact, conditioned medium of IFN-gamma-treated SMCs was mitogenic for SMCs. Mitogenic activity in the conditioned medium was also detected by an assay using Swiss 3T3 cells, which originate from mice and, therefore, are not responsive to human IFN-gamma. The production of the mitogenic factor was blocked by anti-IFN-gamma antibody. Mitogenicity of the conditioned medium was not eliminated by addition of neutralizing antibody against PDGF, indicating that any autocrine growth factor(s) secreted by IFN-gamma-treated SMCs was not PDGF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450173 TI - Aortic permeability to LDL as a predictor of aortic cholesterol accumulation in cholesterol-fed rabbits. AB - The aim of this study was to investigate the possibility that the permeability characteristics of the arterial wall are related to the development of atherosclerosis. The in vivo regional variation of aortic permeability to iodinated human low density lipoprotein (LDL) in normal rabbits was compared with the regional variation in aortic cholesterol accumulation in cholesterol-fed rabbits. Aortas were divided into the aortic arch, thoracic aorta, and abdominal aorta, and each of these three parts was further subdivided into four segments of similar size. The permeability to LDL was 40 +/- 7 nl.cm-2.hr-1 (mean +/- SEM, n = 11) in the most proximal segment of the aortic arch and decreased throughout the length of the aorta to 3 +/- 1 nl.cm-2.hr-1 in the most caudal segment of the abdominal aorta. In such normal rabbits the aortic cholesterol content was similar in all 12 arterial segments at 0.08 +/- 0.005 mumol/cm2 (mean +/- SEM, n = 3 x 12). Aortic cholesterol accumulation was determined in other rabbits with an average plasma cholesterol level of 32 +/- 1 mmol/l for 96 days; the cholesterol content in the most proximal segment of the aortic arch was 2.7 +/- 0.5 mumol/cm2 (mean +/- SEM, n = 11) and decreased with increasing distance from the heart to 0.17 +/- 0.03 mumol/cm2 in the most caudal segment of the abdominal aorta. Linear regression analysis showed a close positive association between the permeability to LDL of a given aortic segment and the cholesterol accumulation in that same aortic segment after cholesterol feeding (r2 = 0.96, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450174 TI - LDL particle size distribution. Results from the Framingham Offspring Study. AB - Using 2-16% gradient gel electrophoresis, we examined low density lipoprotein (LDL) particle size in relation to plasma lipoproteins in 1,168 women and 1,172 men from the Framingham Offspring Study. In addition, we studied the effect of dietary intake on LDL size in a subset of the population. Seven LDL size peaks were identified, with the largest, LDL 1, being found in the density range 1.019 1.033 g/ml; LDL 2 and LDL 3 in d = 1.033-1.038 g/ml; LDL 4 and LDL5 in d = 1.038 1.050 g/ml; and the smallest, LDL 6 and 7, in d = 1.050-1.063 g/ml. Seventy-seven percent of the population had one major and at least one minor LDL peak. Secondary LDL peaks accounted for 23% of the total LDL relative area, based on laser scanning densitometry. LDL size distribution was skewed toward larger LDL particles in women (prevalence of LDL 1, 30% and of LDL 2, 31%), whereas men exhibited a more symmetric distribution (prevalence of LDL 3, 42%). The prevalence of small (< 255 A), dense (d > 1.038 g/ml) LDL particles 4-7 was 33% in men, 5% in premenopausal women, and 14% in postmenopausal women. In agreement with previous reports, small, dense LDL particles were significantly (p < 0.0001) associated with increased triglyceride and apolipoprotein (apo) B levels and decreased HDL cholesterol and apo A-I levels. In addition, we found a significant (p < 0.0001) association between LDL cholesterol and LDL size. The highest LDL cholesterol levels were found among women with LDL 4 (148 mg/dl) and men with LDL 3-5 (138 mg/dl). In addition, the presence of LDL 3 or 4 as secondary peaks was significantly associated with higher LDL cholesterol levels, while smaller secondary LDL peaks were associated with higher triglyceride levels. We also found that compared with subjects with optimal LDL cholesterol levels (< 130 mg/dl), individuals with high-risk LDL cholesterol levels (> or = 160 mg/dl) had 1) a higher prevalence of LDL 3 and 4 (women only) and a lower prevalence of LDL 1 and 2 (women only) and 2) 11% higher LDL cholesterol to apo B ratios, even when matched for LDL particle size. Furthermore, low saturated fat and cholesterol intakes were significantly associated (p < 0.01) with smaller LDL particles. Therefore, the identification of small, dense LDL particles per se may not be a good indicator of coronary artery disease risk in population studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1450175 TI - Thrombogenicity and procoagulant activity of human mesothelial cells. AB - Cell seeding may decrease the thrombogenicity of implanted vascular grafts, but its application is hampered by the limited availability of autologous endothelial cells. We studied the interaction of alternate cells, human peritoneal mesothelial cells, with whole blood in a flow chamber. When citrated blood was perfused over mesothelial cells, platelet adhesion was seen on the intercellular matrix but not on the cells themselves. Perfusions with blood anticoagulated with low-molecular-weight heparin resulted in fibrin formation at the surface of mesothelial cells but not at the surface of human umbilical venous endothelial cells. At shear rates of 200 sec-1 fibrin deposition on the mesothelial cell surface increased during the first 5 minutes to 5.7 +/- 1.06 micrograms fibrin per square centimeter, whereafter these values stabilized. The procoagulant activity of cultured mesothelial cells was higher than that of peritoneal membrane studied ex vivo. However, cultured mesothelial cells incubated with polyclonal antibodies against tissue factor showed a significant decrease in procoagulant activity. We conclude that human peritoneal mesothelial cells may be used for cell seeding procedures, provided that their tissue factor expression can be controlled. PMID- 1450176 TI - Polarized binding of lipoprotein lipase to endothelial cells. Implications for its physiological actions. AB - Lipoprotein lipase (LPL) that is associated with the luminal surface of capillary endothelial cells hydrolyzes circulating lipoprotein triglyceride molecules. Because LPL is synthesized by cells on the abluminal side of endothelial cells, LPL must contact both the abluminal as well as the luminal sides of the endothelium. To determine whether LPL interacts identically with apical (luminal) and basolateral (abluminal) sides of endothelial cells, we investigated binding, transport, and cellular uptake of LPL presented to each side of bovine aortic endothelial cell monolayers grown on semipermeable filters. When LPL was included in the medium on either the apical or basolateral side of the cells, a similar amount of LPL was found in the medium on the opposite side of the cells. Heat inactivated LPL crossed the monolayers more rapidly in both directions. When cell surface LPL was assessed, more LPL bound to the apical than the basolateral endothelial cell surface. Release of cell surface-associated LPL was assessed with the use of heparin. Less heparin was required to dissociate apical-surface LPL. When LPL (4 micrograms/ml) was in contact with the apical surface for 1 hour, 32.8 +/- 4.9 ng LPL per 24-mm filter were internalized by the cells. If the LPL was in the basolateral medium, only 6 +/- 1.8 ng LPL were found inside the cells. Heat inactivation decreased LPL binding to cell surfaces and internalization by the cells. LPL interactions with the cells were also studied morphologically by using Texas Red (TR)-labeled LPL and confocal microscopy. More TR-LPL was associated with and internalized by the apical endothelial surface. Incubation of cells with TR-LPL in the basolateral medium led to accumulation of LPL on the apical surface, suggesting that the LPL was transported across the cells. Inclusion of TR-LPL on the apical surface did not lead to appreciable accumulation of LPL on the basolateral cell surface. Therefore, endothelial cells are polarized to accumulate LPL on the apical surface. In addition, more LPL is internalized from this side of the cells. We postulate that the polarity of endothelial cells allows LPL to collect at its physiological site of action, i.e., on the luminal surface. PMID- 1450177 TI - Regulation of lipoprotein lipase secretion in murine macrophages during foam cell formation in vitro. Effect of triglyceride-rich lipoproteins. AB - Triglyceride rich-lipoproteins induce triglyceride accumulation in macrophages, leading to foam cell formation. The correlation between cell triglyceride accumulation and lipoprotein lipase (LPL) secretion in murine macrophages and the role that LPL plays in the accumulation process were examined. LPL secretion is defined as the extracellular LPL activity that accumulates during a 4-hour incubation of treated and untreated cells in a bovine serum albumin-containing RPMI-1640 medium. LPL secretion was suppressed (up to 70%) in a dose- and time dependent manner when J774.1 cells were incubated with chylomicrons, very low density lipoproteins, and intermediate density lipoproteins but not with low or high density lipoproteins from normolipidemic and hypertriglyceridemic subjects. Oleic acid both suppressed LPL secretion and invoked triglyceride accumulation. Suppression of LPL secretion preceded gross triglyceride accumulation, was reversible, and was not the result of a reduction in LPL mRNA. P388D1 cells neither secreted LPL nor accumulated triglyceride. Inhibition of LPL secretion by tunicamycin in both peritoneal macrophages and J774.1 cells prevented a hypertriglyceridemic very low density lipoprotein-induced triglyceride accumulation, an effect that was counteracted by addition of exogenous LPL. The results suggest that 1) extracellular hydrolysis of lipoprotein triglyceride is a major factor in inducing foam cell formation and 2) LPL secretion may be regulated by cell energy needs, and when these needs are exceeded, LPL secretion is suppressed. PMID- 1450178 TI - Familial correlations of HDL subclasses based on gradient gel electrophoresis. AB - We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the familial correlations of high density lipoprotein (HDL) subclasses for 150 offspring in 47 nuclear families. The absorbance of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDL3c (7.2-7.8 nm), HDL3b (7.8-8.2 nm), HDL3a (8.2-8.8 nm), HDL2a (8.8-9.7 nm), and HDL2b (9.7-12 nm). Parent-offspring correlations were computed for two different characterizations of the parents: 1) by sex (i.e., mother versus father) and 2) by their relative values (highest versus lowest HDL). Sibling resemblance was assessed by using the intraclass correlations coefficient. Family members were significantly related for the following subclasses: HDL3c (sibling and father-offspring), HDL3b (sibling), HDL3a (sibling and mother-offspring), HDL2a (mother-offspring), and HDL2b (sibling, father-offspring, and mother offspring). The offsprings' HDL3c and HDL2b values were more strongly related to their fathers' than to their mothers' values, whereas their HDL2a levels were more strongly related to their mothers' than their fathers' values. In addition, fathers' HDL2b levels were inversely correlated with the offsprings' HDL3b. The parents' HDL subclass levels were more strongly related to subclass levels of their younger (< or = 20 years) than their older offspring. Among all subclasses, HDL2b showed the strongest parent-offspring relation, with the parents' HDL values accounting for over 30% of the variance in offsprings' HDL2b.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450179 TI - Activation of platelets in blood perfusing angioplasty-damaged coronary arteries. Flow cytometric detection. AB - Fluorescence-activated flow cytometry has been used to investigate platelet activation in blood flowing through atherosclerotic coronary arteries after sustaining mechanical damage induced by percutaneous transluminal angioplasty (PTCA). For flow cytometry, platelets and platelet-derived microparticles were identified by biotinylated anti-glycoprotein (GP) Ib monoclonal antibody (mAb) and a fluorophore, phycoerythrin-streptavidin. Activated platelets were detected by using a panel of fluoresceinated mAbs specific for activation-dependent platelet epitopes, including 1) activated GPIIb-IIIa complex (PAC1); 2) fibrinogen bound to platelet GPIIb-IIIa (9F9); 3) ligand-induced binding sites on GPIIIa (anti-LIBS1); and 4) P-selectin, an alpha-granule membrane protein expressed on the platelet surface after secretion (S12). The binding of antibodies to platelets was determined in blood that was sampled continuously via heparin-coated catheters from the coronary sinus in 1) patients before, during, and for 30 minutes after PTCA and 2) control patients undergoing coronary angiography without PTCA. Platelets in coronary sinus blood showed significant binding of mAbs that specifically detect activation epitopes associated with the GPIIb-IIIa complex (PAC1, anti-LIBS1, and 9F9) during and for 30 minutes after angioplasty in four of the five patients. The relative proportion of platelets positive for PAC1 and anti-LIBS1 increased from baseline values of 2.0 +/- 0.3% (mean +/- SD) and 2.0 +/- 0.5% to 18 +/- 14% and 28 +/- 14%, respectively, during PTCA or 30 minutes after PTCA (p < 0.01 in both cases). Binding with 9F9 was less prominent. The expression of P-selectin was detected in one of the five patients. By contrast, activation-specific mAbs failed to bind detectably with platelets obtained from 1) the peripheral blood during coronary angiography in eight patients or 2) coronary sinus blood obtained via catheter throughout control catheterization procedures in three patients or before PTCA in five. We conclude that circulating platelets become activated while flowing through PTCA-damaged stenotic coronary arteries and that this process of platelet activation is readily demonstrated by measuring the expression of activation-specific membrane GP epitopes by flow cytometric analysis. PMID- 1450180 TI - Pituitary factors in blood plasma are necessary for smooth muscle cell proliferation in response to injury in vivo. AB - Intimal thickening in response to vascular injury is inhibited in animals previously subjected to hypophysectomy. We have investigated the nature and cell kinetics of this effect in a balloon catheter model of injury to the rat carotid artery. The ability of injury to stimulate [3H]thymidine labeling 48 hours after injury was almost completely eliminated in hypophysectomized (hypox) compared with control animals (0.1% versus 32.1%). Total DNA content of the developing neointima 14 days after injury was only 30% of the values found in ballooned carotid arteries of normal rats. If hypox rats were treated with recombinant human growth hormone, the proliferative response was not restored. There are two possible general explanations for the reduction of proliferative response in hypox animals: 1) that smooth muscle cells in the hypox animals have lost the ability to respond to the stimulus of injury or 2) that the ability of the smooth muscle cells to respond has not been reduced by prior hypophysectomy, but that the response itself requires the presence of pituitary-dependent factors. Transplantation experiments were performed in vivo to distinguish between these possibilities. Carotid arteries in inbred Lewis rats were excised 1 hour after balloon injury to give platelets the opportunity to adhere. These vessels were then transplanted from hypox into control animals and vice versa. At 48 hours, proliferation of smooth muscle cells in "control-to-hypox" transplants was 0.3% compared with 14.3% in "control-to-control" transplants, whereas vessels from hypox rats increased their indices to 4.8% if transplanted into control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450181 TI - LDL subclass phenotypes and triglyceride metabolism in non-insulin-dependent diabetes. AB - Plasma low density lipoprotein (LDL) comprises multiple discrete subclasses differing in size, density, and chemical composition. A common, heritable phenotype characterized by the predominance of small, dense LDL particles (LDL subclass phenotype B) is associated with relatively increased concentrations of plasma triglycerides, reduced levels of high density lipoprotein, and increased risk of coronary artery disease in comparison with subjects with larger LDL (LDL subclass phenotype A). Population studies have indicated that approximately 20 30% of adult men have phenotype B, and another 15-20% have LDL of intermediate size. The lipid changes in phenotype B are similar to those that have been observed in patients with non-insulin-dependent diabetes mellitus (NIDDM). In the present study, we have assessed LDL subclass phenotypes in normolipidemic men with NIDDM and in age-matched control subjects who had similar lipid levels. There was a greater than twofold increase in the percentage of individuals with the LDL B phenotype in the NIDDM subjects. The LDL B phenotype was associated with higher plasma triglyceride levels and a trend toward lower high density lipoprotein cholesterol levels compared with the LDL A phenotype in the NIDDM subjects, as has been previously observed in control groups. Indices of diabetic control, such as fasting and hemoglobin A1 levels, were similar regardless of LDL phenotype pattern, suggesting that glycemic control was not likely to account for the increase in the LDL B phenotype. In both control and NIDDM subjects, the clearance of triglyceride-rich lipoproteins was slowed in the subjects with the LDL phenotype B compared with those with the A phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450182 TI - Altered susceptibility to in vitro oxidation of LDL in LDL complexes and LDL aggregates. AB - Low density lipoprotein (LDL) is known to form complexes with polysulfated compounds, like heparin, dextran sulfate (DS), and chondroitin sulfate. In particular, chondroitin 6-sulfate (C6S)-rich proteoglycans of the arterial intima can associate with LDL, resulting in accumulation of LDL in atherosclerotic lesions. Besides LDL complex formation, LDL self-aggregation has been recently suggested to play a role in atherogenesis. Oxidative modification of LDL has also been implicated as a factor in the generation of the atherosclerotic plaque. Assuming that LDL self-aggregation may alter the molecule's susceptibility to oxidative modification, we have studied the sensitivity of LDL in LDL a aggregates as well as in insoluble and soluble LDL-C6S, LDL-heparin, and LDL-DS complexes to in vitro oxidation by cooper ions. Complexing the LDL with C6S and heparin resulted in an increased susceptibility of LDL to in vitro oxidation, whereas the oxidation of LDL complexed with DS was unaffected. In great contrast to the oxidation of LDL in LDL complexes, the in vitro oxidation of LDL in LDL aggregates (self-aggregation by denaturation) was strongly reduced. The results suggest that complex or aggregate formation may alter the susceptibility of the lipoprotein to oxidative modification and finally its metabolic fate or biological activity. PMID- 1450183 TI - Augmented arterial wall expression of type-1 plasminogen activator inhibitor induced by thrombosis. AB - Type-1 plasminogen activator inhibitor (PAI-1), the primary physiological inhibitor of endogenous plasminogen activators, modulates fibrinolysis, cell migration, and tissue repair. To determine whether genetic expression of PAI-1 is augmented in the walls of vessels exposed to thrombi but not to a direct physical insult such as electrical injury, we induced arterial thrombosis in rabbit carotid arteries with intraluminal surgical silk sutures and performed in situ hybridization for PAI-1 messenger RNA (mRNA) and immunohistochemistry for PAI-1 antigen at selected intervals. PAI-1 activity in plasma remained virtually constant. In contrast, PAI-1 mRNA increased in endothelial cells juxtaposed to thrombi, in smooth muscle cells adjacent to the neointima, and in macrophages surrounding the suture material. PAI-1 protein was detected in regions in which PAI-1 mRNA was expressed. The increased expression of PAI-1 mRNA colocalized with PAI-1 protein in the endothelium juxtaposed to thrombi may potentiate thrombosis by shifting the local balance between fibrinolysis and thrombosis toward thrombosis. Furthermore, it may alter vascular remodeling and predispose to stenosis after interventions such as angioplasty, in which local thrombosis cannot be avoided. PMID- 1450184 TI - Increased lipid binding to thrombi in coronary artery disease. Findings in patients without premedication in native (not anticoagulated) test systems. AB - Thrombi and clots were produced from native (i.e., not anticoagulated) platelet rich and platelet-poor plasma from patients with coronary artery disease and control subjects who had not taken any medication known to influence plasma lipids, coagulation, or platelet aggregation. The clotting times were recorded, and the lipid content of clots, thrombi, platelets, plasma, and high density lipoprotein was analyzed. Thrombi produced from native platelet-rich plasma were 46% heavier in coronary artery disease patients and contained about 20% more phospholipids and free cholesterol and about twice the amount of triglycerides and esterified cholesterol in both absolute and relative amounts with respect to the corresponding lipids of plasma plus platelets. The elevated content of lipids not only increases the size of the thrombi but also changes their quality because of an increased content in plasmatic lipids, as platelets contain only trace amounts of triglycerides and cholesterol esters. In agreement herewith, fibrinogen and maximal amplitude on the thrombelastogram were increased in coronary artery disease patients, whereas the thrombus-forming time and clotting times of platelet-poor and platelet-rich plasma were shortened, indicating accelerated coagulation and activation of platelets. Analysis of these results suggests a disturbed interrelation in coronary artery disease between lipids and hemostasis, in which platelets, high density lipoprotein, and lipoproteins rich in triglycerides and cholesterol esters may play a role. PMID- 1450185 TI - Matching clinical and biological specificity: implications for biological psychiatry. PMID- 1450186 TI - A dose-finding study with remoxipride in the acute treatment of schizophrenic patients. AB - Two hundred and forty-two patients with acute schizophrenia were enrolled in a double-blind, comparative, dose-finding study of a novel antipsychotic, remoxipride. Remoxipride was evaluated in a low (30 to 90 mg), medium (120 to 240 mg) and a high (300 to 600 mg) dose range and compared with a haloperidol (15 to 45 mg), which was administered to a similar group of patients. The results support the antipsychotic effect of remoxipride, with maximum efficacy occurring at daily doses between 120 mg and 600 mg. Side-effects were more frequent at doses of remoxipride over 300 mg. In all groups, remoxipride caused consistently fewer extrapyramidal side-effects than haloperidol. The antipsychotic effect of remoxipride may be derived from specific blockade of dopamine D2 receptors in the mesolimbic tract. The findings also suggest that remoxipride may have a therapeutic effect on negative symptoms of schizophrenia. PMID- 1450187 TI - The varied adult psychopathologies of children's behavior disorders. AB - Thirteen percent of the general population show the traits of emotional over reactivity, emotional lability and impulsiveness that appear to be genetically transmitted. The troublesome manifestation of these traits can often be medically controlled, thereby reducing their costs to society. PMID- 1450189 TI - Importance of maintaining normal nasal function in the cleft palate patient. AB - The external nose is a structure that provides prominence to the face. The internal nose is a paired nasal cavity that extends from the face to the pharynx. Turbinates are major structures within the lateral walls of the nose. They perform the major functions of the nose that include respiration, humidification, temperature regulation, and filtration of the inspired air. Conditions that obstruct the nose interfere with its optimal function. These range from acute or chronic infection to enlarged tonsils and adenoid tissue to nasal septal deviation. Surgeons caring for patients with clefts must have familiarity with nasal anatomy and function and conditions that alter them. Correction of these conditions may require medical and/or surgical treatment. PMID- 1450190 TI - Navigation of the nose with flexible fiberoptic endoscopy. AB - The introduction of flexible fiberoptics into medicine revolutionized the evaluation and treatment of velopharyngeal dysfunction. In this paper, rigid endoscopy and flexible fiberoptic scopes are discussed, including their respective advantages and disadvantages. Anesthetic and anatomic considerations relative to the endoscopic procedure are presented. Transnasal endoscopy permits documentation of static and dynamic anatomy, information that may be fundamental for the understanding and treatment of patients with velopharyngeal dysfunction. PMID- 1450191 TI - Nasal airway in breathing and speech. AB - Clefts of the lip and palate frequently produce nasal deformities that tend to reduce the size of the nasal airway. Approximately 70% of the cleft population have nasal airway impairment and about 80% "mouth-breathe" to some extent. Surgical correction of nasal, palatal, and pharyngeal structures may further compromise breathing. Type of cleft appears to affect airway size, with unilateral clefts demonstrating the smallest airway. Although a pharyngeal flap may further decrease airway size, some individuals do not notice a postoperative change because of airway compromise prior to flap placement. Speech is a modified breathing behavior that uses the respiratory system to provide an energy source and involves structures within the respiratory tract to modulate this energy into meaningful sounds. The oral, nasal, and pharyngeal structures that are affected by cleft lip and palate during breathing are often compromised for speech as well. The nasal airway plays an important role in controlling speech pressures when velopharyngeal function is impaired. A "good" nose for breathing is often a "bad" nose for speech under such circumstances. PMID- 1450188 TI - Dopamine receptor genes: new tools for molecular psychiatry. AB - For over a decade it has been generally assumed that all the pharmacological and biochemical actions of dopamine within the central nervous system and periphery were mediated by two distinct dopamine receptors. These receptors, termed D1 and D2, were defined as those coupled to the stimulation or inhibition of adenylate cyclase, respectively, and by their selectivity and avidity for various drugs and compounds. The concept that two dopamine receptors were sufficient to account for all the effects mediated by dopamine was an oversimplification. Recent molecular biological studies have identified five distinct genes which encode at least eight functional dopamine receptors. The members of the expanded dopamine receptor family, however, can still be codifed by way of the original D1 and D2 receptor dichotomy. These include two genes encoding dopamine D1-like receptors (D1 [D1A]/D5 [D1B]) and three genes encoding D2-like receptors (D2/D3/D4). We review here our recent work on the cloning and characterization of some of the members of the dopamine receptor gene family (D1, D2, D4, D5), their relationship to neuropsychiatric disorders and their potential role in antipsychotic drug action. PMID- 1450192 TI - Acoustic assessment of the nasal airway. AB - Instrumental assessment techniques are needed to acquire quantitative information concerning the form and function of the nasal cavity. Until recently, aerodynamic methods were virtually the only source of such information. Two additional instruments are now available that purport to provide information useful to clinicians interested in assessing nasal form and function. This paper describes both the Nasometer and the acoustic rhinometer. In addition, a more traditional measure involving acoustic analysis of nasal consonants is discussed. Both the known and potential benefits and limitations of each technique are discussed. PMID- 1450193 TI - History of cleft lip nasal repair. AB - Surgery of the cleft lip nasal tip has lagged behind cleft lip surgery. In fact, in most early illustrations it was not even noted. Since the development of cosmetic rhinoplasty an endless array of techniques have been published. Unfortunately there are few studies of the gross anatomy. PMID- 1450194 TI - Congenital clefts of the nose: principles of surgical management. AB - Congenital clefts of the nose are rare and highly variable. Because there are few examples, standard methods for treatment do not exist. Therefore each patient must be evaluated and managed individually with respect to anatomic elements, timing, and sequence of reconstruction. PMID- 1450195 TI - Correction of the bilateral cleft lip nasal deformity: evolution of a surgical concept. AB - The origin of the nasal deformity of a bilateral complete cleft lip is both primary (deformation/malformation) and secondary (postoperative distortion). This is an interim report of a personal evolution from staged correction of the bilateral cleft nasal deformity to synchronous repair of the nose and the lip and premaxillary-maxillary clefts. The anatomic concept is that, because of the malpositioned alar cartilages, the columella only appears to be short in an infant with bilateral cleft lip. The technical stratagems to model the nose are: (1) alignment of the premaxilla and (2) anatomic placement of the alar cartilages with sculpturing of the overlying soft tissue. PMID- 1450196 TI - Effects of orthognathic surgery on nasal form and function in the cleft patient. AB - Management of common problems of nasal airway obstruction in cleft and noncleft patients by the subnasal approach through the maxillary Le Fort I osteotomy are discussed. The effects of maxillary surgical repositioning on the esthetics of the nose and upper lip are presented, as well as the sequencing and timing of orthognathic surgery and nasal reconstruction in the cleft patient. Case presentations illustrate the results of this treatment approach. PMID- 1450197 TI - Early and late treatment of unilateral cleft nasal deformity. AB - Surgical techniques have been developed to correct nasal deformity associated with unilateral cleft lip, alveolus, and palate. This deformity can be significantly corrected during the primary cleft lip repair, as performed by the technique described by the author. Secondary corrective procedures focus mostly on skeletal support and lining distortions as well as on rearrangements of lower lateral cartilages. At the final stage, esthetic appearance can be significantly improved by contour remodeling with the addition of cartilage and/or bony implants. Choice of surgical technique depends upon the severity of the deformity and the experience and proficiency of the surgeon. At the present time, correction of the nasal deformity associated with a unilateral cleft is an integral part of primary cleft lip repair and part of multidisciplinary management of cleft deformities. PMID- 1450198 TI - Clinician activism and ethical restraints in providing treatment: preventive as opposed to reconstructive approaches. AB - There is seldom controversy when faced with treatment decisions for a child born with a birth defect. Occasionally, the situation arises in which a decision to withhold treatment must be made. Under most circumstances the responsibility for making such decisions rests with the child's parents or guardians, since it is generally felt that these individuals are the best advocates for the child's best interests. In order to make such difficult decisions, the parents are dependent upon the guidance and counseling of health professionals, especially the physicians most closely involved in each case. The ultimate decisions made by parents are dependent upon open and unambiguous communication with their children's clinicians as well as open communications among the caregivers themselves. The role of the clinician as an advocate for treatment and nontreatment of children is dependent upon clear unbiased communication and the desire to do what is in the best interest for each patient. PMID- 1450199 TI - Management of major craniofacial anomalies: a pediatric perspective. AB - Ethical decision-making regarding complex congenital anomalies has evolved along with improvements in neonatal medical and surgical care, but also reflects a changed medical and social environment. The current process is complex and cumbersome, with no guarantee of consensus, and frequently leads to indecision and disagreement. Improvement of the process will require continued professional education, as well as better reconciliation of areas of ambivalence among professionals, families, and society. PMID- 1450200 TI - Social and psychological effects of major craniofacial deformity. AB - This paper discusses the social and psychological experiences of patients with the most severe forms of craniofacial deformity. The paper concludes that individuals with the most severe forms of craniofacial deformities are at risk for experiencing social and psychological stress and for having their quality of life negatively impacted by the experience of having a facial deformity. Much of the stress experienced by these individuals is the result of the negative social response to their facial deformity. It is emphasized that many patients will not develop psychopathology, because of intervening personality and family factors that may ameliorate these negative social stressors. The excellent progress made in assessing, preventing, and treating the negative psychosocial impact of facial deformity is noted. Finally, in attempting to understand the impact of facial deformity on quality of life, emphasis is placed on the subjective evaluation of these factors by each individual patient and family. PMID- 1450201 TI - Ethical and health policy issues in the treatment of children with major craniofacial deformities. AB - The advent of craniofacial surgery and neonatal intensive care has made it possible for children with serious craniofacial deformities to live and possibly to experience effective habilitation. These therapeutic innovations also raise important social and ethical issues that are rarely examined. This paper reviews the dilemmas that relate to the gatekeeper role for physicians, the impact of prenatal diagnosis, and the allocation of scarce fiscal and health resources to craniofacial care. The high degree of cost, the intense investment of medical resources, and the uncertain outcomes in the care of children with major craniofacial deformities, must be considered in the distribution of resources within a health system. The rationing of health resources is discussed as a future determinant of how care for major craniofacial deformities may be delivered in the United States. PMID- 1450202 TI - Trafficking of glycosphingolipids in eukaryotic cells; sorting and recycling of lipids. PMID- 1450203 TI - Cytoplasmic Ca2+ oscillations in pancreatic beta-cells. AB - In the last 15 years it has been a growing interest in the cyclic variations of circulating insulin [46]. After the suggestion that this phenomenon may be due to oscillations of the beta-cell membrane potential [8,39], it was demonstrated that [Ca2+]i oscillates in the glucose-stimulated beta-cell with a similar frequency to that of pulsatile insulin release. The present review describes four types of [Ca2+]i oscillations in the pancreatic beta-cell. The slow sinusoidal oscillations, referred to as type-a, are those which most closely correspond to pulsatile insulin release. Although not affecting the properties of the type-a oscillations in individual beta-cells, the concentration of glucose is a determinant for their generation and further transformation into a sustained increase. Accordingly, cytoplasmic Ca2+ is regulated by sudden transitions between oscillatory and steady-state levels at threshold concentrations of glucose, which are characteristic for the individual beta-cell. This behaviour explains the observation of a gradual recruitment of previously non-secreting cells with increase of the extracellular glucose concentration [44]. However, it still remains to be elucidated how the sudden transitions between these three states translate into the co-ordinated slow oscillations of [Ca2+]i in the intact islet. Cyclic variations of circulating insulin require a synchronization of the [Ca2+]i cycles also among the islets in the pancreas. It is still an open question by which means the millions of islets communicate mutually to establish a pattern of pulsatile insulin release from the whole pancreas. The discovery that the beta-cell is not only the functional unit for insulin synthesis but also generates the [Ca2+]i oscillations required for pulsatile insulin release has both physiological and clinical implications. The fact that minor damage to the beta-cells prevents the type-a oscillations with maintenance of a glucose response in terms of raised [Ca2+]i reinforces previous arguments [54] that loss of insulin oscillations is an early indicator of type-2 diabetes. Further analyses of the [Ca2+]i oscillations in the beta-cells should include not only the mechanisms for their generation and subsequent propagation within or among the islets but also how modulation of their frequency affects the insulin sensitivity of various target cells. The latter approach may be important in the attempts to maintain normoglycemia under conditions minimizing the vascular effects of insulin supposed to precipitate hypertonia and atherosclerosis [70,71,77]. PMID- 1450204 TI - Immunologic aspects of liposomes: presentation and processing of liposomal protein and phospholipid antigens. PMID- 1450205 TI - Contributions of chemical derivatization and spectroscopic studies to the characterization of the Ca2+ transport ATPase of sarcoplasmic reticulum. PMID- 1450206 TI - Crystal structures of membrane lipids. PMID- 1450208 TI - Analysis of the binding of polymyxin B to endotoxic lipid A and core glycolipid using a fluorescent displacement probe. AB - Dansylcadaverine, a cationic fluorescent probe binds to bacterial lipopolysaccharide and lipid A, and is displaced competitively by other compounds which possess affinity toward endotoxins. The binding parameters of dansylcadaverine for lipid A were determined by Scatchard analysis to be two apparently equivalent sites with apparent dissociation constants (Kd) ranging between 16 microM to 26 microM, while that obtained for core glycolipid from Salmonella minnesota Re595 yielded a Kd of 22 microM to 28 microM with three binding sites. The Kd of polymyxin B for lipid A was computed from dansylcadaverine displacement by the method of Horovitz and Levitzki (Horovitz, A., and Levitzki, A. (1987) Proc. Natl. Acad. Sci. USA 84, 6654-6658). The applicability of this method for analyzing fluorescence data was validated by comparing the Kds of melittin for lipid A obtained by direct Scatchard analysis, and by the Horovitz-Levitzki method. The displacement of dansylcadaverine from lipid A by polymyxin B was distinctly biphasic with Kds for polymyxin B-lipid A interactions corresponding to 0.4 microM and 1.5 microM, probably resulting as a consequence of lipid A being a mixture of mono- and di-phosphoryl species. This was not observed with core glycolipid, for which the Kd for polymyxin was estimated to range from 1.1 microM to 5.8 microM. The use of dansylcadaverine as a displacement probe offers a novel and convenient method of quantitating the interactions of a wide variety of substances with lipid A. PMID- 1450209 TI - Persistence of increased cholesteryl ester in human skin fibroblasts is caused by residual exogenous sphingomyelinase and is reversed by phospholipid liposomes. AB - Human skin fibroblasts (HSF) were exposed to sphingomyelinase 50 or 5 mU/ml for 60 min, washed with 5 mM EDTA or 20% serum and with phosphate-buffered saline, and postincubated for 24 h in the presence of [14C]16:0 sphingomyelin (SP) liposomes. The recovery of up to 48% of label in the medium in ceramide provided evidence of persistence of sphingomyelinase activity. The rate of hydrolysis of [14C]16:0 SP remained the same irrespective of whether the liposomes were added immediately after the wash, or 3 or 6 h thereafter. In HSF labeled with [3H]cholesterol exposure to 50 mU/ml of sphingomyelinase for 60 min resulted in an increase in labeled cholesteryl ester (CE) at 6 and 24 h of postincubation. Addition of sphingomyelin liposomes reduced markedly the fraction of cellular labeled cholesteryl ester recovered after 24 h, while phosphatidylcholine liposomes were not effective. When the enzyme concentration had been reduced 5-20 fold the effect of sphingomyelin liposomes on cellular 3H-CE was evident already after 6 h of postincubation and some effect was seen also with phosphatidylcholine liposomes. Increase in the concentrations of SP liposomes to 150 micrograms/ml restored labeled cholesteryl ester to control values at 24 h. A significant reduction occurred also with 18:1 phosphatidylcholine liposomes but labeled cholesteryl ester remained 50-100% higher when compared with 18:1 or 18:2 SP. No correlation was seen between the rates of cholesteryl ester decrease and free cholesterol efflux into the medium. The inability to remove residual sphingomyelinase by regular washing procedures exaggerates and prolongs the recovery period of sphingomyelin during postincubation and delays the return of the cholesteryl ester pool to control levels. This can be counteracted by addition of phospholipid liposomes that can compete for the enzyme with the plasma membrane sphingomyelin and also substitute the hydrolyzed molecule in the plasma membrane to impede cholesterol flow to cell interior. PMID- 1450207 TI - Spontaneous lipid transfer between organized lipid assemblies. PMID- 1450210 TI - Structural elucidation of a novel phosphonoglycosphingolipid in eggs of the sea hare Aplysia juliana. AB - A novel phosphonoglycosphingolipid (AJPnGL) was isolated from eggs of the sea hare Aplysia juliana. The structure was determined to be Gal alpha 1-->2Gal beta 1-->4(2-aminoethylphosphonyl-->6)Glc beta 1-->1Cer by FAB/MS, 1H-NMR, hydrogen fluoride degradation, methylation analysis, partial acid hydrolysis and GC analysis of the component sugars, fatty acids and long-chain bases. The ceramide moiety of this lipid consisted of branched nonadeca-4-sphingenine and octadeca-4 sphingenine as main long-chain bases and palmitic acid and stearic acid as major fatty acids. Since the sugar chain (Gal alpha 1-->2Gal beta 1-->4Glc beta 1-->) and the ceramide moiety of AJPnGL were identical with those of the main neutral glycosphingolipid of eggs of A. juliana, the biosynthesis of AJPnGL may occur by the addition of 2-aminoethylphosphonate to the main neutral glycosphingolipid, Gal alpha 1-->2Gal beta 1-->4Glc beta 1-->1Cer. PMID- 1450211 TI - Multiple phospholipase A2 activities in canine vascular smooth muscle. AB - Three phospholipase A2 activities from canine vascular smooth muscle were identified and characterized including: (1) a cytosolic calcium-independent phospholipase A2 which is activated by nucleotide di- and triphosphates; (2) a cytosolic calcium-dependent phospholipase A2 which is activated by physiologic increments in calcium ion concentration; and (3) a microsomal calcium-independent phospholipase A2 which was highly selective for plasmenylcholine substrate. Vascular smooth muscle cytosolic calcium-independent phospholipase A2 was activated 338% +/- 11 (X+S.E.; n = 15) by physiologic concentrations of ATP. Similar amounts of activation were also present utilizing other nucleotide di- and triphosphates (e.g., ADP, CTP, GDP and GTP) as well as non-hydrolyzable nucleotide triphosphate analogs (e.g., ATP-gamma-S, AMP-PNP and GTP-gamma-S). Vascular smooth muscle cytosolic calcium-dependent phospholipase A2 was purified 455-fold by sequential DEAE-Sephacel, Phenyl-Sepharose, Mono Q, hydroxyapatite and Superose 12 chromatographies. The partially purified calcium-dependent phospholipase A2 was activated by physiologic increments in calcium ion concentration (e.g., 1 microM) and possessed an apparent native molecular weight of 95 kDa, an acidic isoelectric point (pI = 4.8) and a neutral pH optimum (pH 7.0). Vascular smooth muscle microsomal phospholipase A2 activity was predominantly calcium-independent and was over six-fold selective for hydrolysis of plasmenylcholine substrate. Taken together, these results demonstrate the existence of three separate and distinct phospholipase A2 activities in vascular smooth muscle and identify ATP and calcium ion as independent modulators of discrete phospholipase A2 activities in vascular smooth muscle cells. PMID- 1450213 TI - In vivo phospholipid modification induces changes in microsomal delta 5 desaturase activity. AB - The phospholipid composition of rat-liver microsomes was modified by feeding weaning rats a choline-free diet. After 21 days, the phosphatidylcholine content decreased with a concomitant increment of phosphatidylserine and cholesterol. The bulk fluidity of the membrane decreased. Under these conditions, the delta 5 desaturase activity was diminished as well as the arachidonic-acid content of the membrane lipids. PMID- 1450212 TI - Structural characteristics of the ceramides of neutral glycosphingolipids in the human female genital tract--their menstrual cycle-associated change in the cervical epithelium and uterine endometrium, and their dissociation in the mucosa of the fallopian tube with the menstrual cycle. AB - In human cervical epithelium, uterine endometrium, and mucosa of the fallopian tubes, neutral glycosphingolipids were exclusively represented by the globo series glycosphingolipids, such as CMH, LacCer, Gb3Cer and Gb4Cer, but the molecular species of their ceramide moieties were characteristically altered in the cervical epithelium and uterine endometrium during the menstrual cycle. Individual neutral glycosphingolipids in the cervical epithelium and the uterine endometrium at the follicular phase gave two bands on TLC, whereas those at the luteal phase displayed three bands, the third being the lower migrating one. Neutral glycosphingolipids migrating to the same positions as these lower migrating bands were constantly detected in the mucosa of the fallopian tubes, independent of the menstrual cycle. The lower-migrating bands for the cervical epithelium and the uterine endometrium at the luteal phase were due to molecules mainly constructed of phytosphingosine with alpha-hydroxy fatty acids having chain lengths of 18-24 and 4-sphingenine with alpha-hydroxy fatty acids having chain lengths of 16-22, whereas those in the mucosa of the fallopian tubes were exclusively N-alpha-hydroxypalmitoyl 4-sphingenine. PMID- 1450214 TI - Influence of an increased intake of linoleic acid on the incorporation of dietary (n-3) fatty acids in phospholipids and on prostanoid synthesis in rat tissues. AB - We investigated whether the amount of dietary linoleic acid (LA) (as corn oil) influences the incorporation of dietary eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in tissue phospholipids and the prostanoid biosynthesis. Rats were fed four different levels of corn oil (at a total dietary fat level of either 2.5%, 5%, 10% or 20%); at each corn oil level, two groups of rats were supplemented with either EPA and DHA (200 mg/day) during 6 weeks, and compared with a group receiving oleic acid. The phospholipid fatty acid composition of liver, kidney and aorta showed, as expected, that the incorporation of EPA was highly suppressed by increasing the content of dietary linoleic acid in the diets. On the other hand, DHA was almost unaffected by the amounts of (n - 6) fatty acids in the diets. These results indicate that EPA levels but not DHA levels in tissue phospholipids were influenced by the competing dietary (n - 6) fatty acids. The tissue arachidonate content was similar under the various dietary linoleic acid conditions, but feeding EPA or DHA lowers the AA content. Moreover, the amount of dietary linoleic acid did not significantly influence the prostaglandin E2 (PGE2) production in stimulated aortic rings. However, PGE2 synthesis was significantly decreased in the groups treated with either EPA or DHA. Thromboxane B2 levels in serum followed a similar pattern. It is suggested that an increase of dietary (n - 3) PUFAs is more efficient to reduce (n - 6) eicosanoid formation than a decrease of dietary (n - 6) fatty acids. PMID- 1450215 TI - High-level expression in Escherichia coli and rapid purification of enzymatically active honey bee venom phospholipase A2. AB - Bee venom phospholipase A2 (BV-PLA2) is a hydrolytic enzyme that specifically cleaves the sn-2 acyl bond of phospholipids at the lipid/water interface. The same enzyme is also believed to be responsible for some systemic anaphylactic reactions in bee venom sensitized individuals. To study the structure/function relationships of this enzyme and to define the molecular determinants responsible for its allergenic potential, a synthetic gene encoding the mature form of BV PLA2 was expressed in Escherichia coli. This enzyme was produced as a fusion protein with a 6xHis-tag on its amino-terminus yielding 40-50 mg of fusion protein per 1 of culture after metal ion affinity chromatography. A kallikrein protease recognition site was engineered between the 6xHis-tag and the amino terminus of the enzyme allowing isolation of the protein with its correct N terminus. Recombinant affinity purified BV-PLA2 was refolded, purified to homogeneity, and cleaved with kallikrein, resulting in a final yield of 8-9 mg of active enzyme per 1 of culture. The enzymatic and immunological properties of the recombinant BV-PLA2 are identical to enzyme isolated from bee venom indicating a native-like folding of the protein. PMID- 1450216 TI - Acyl-CoA: cholesterol acyltransferase and 3-hydroxy-3-methylglutaryl-CoA reductase in carp-liver microsomes: effect of cold acclimation on enzyme activities and on hepatic and plasma lipid composition. AB - Hepatic microsomal activities of acyl-CoA:cholesterol acyltransferase (ACAT) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, rate-limiting enzymes in cholesterol esterification and cholesterol synthesis, and the concentration sand compartmentalization of esterified and unesterified cholesterol, were studied in carp acclimated to 10 and 30 degrees C. Irrespective of acclimation temperature, carp-liver ACAT is characterized by an apparent Km-value for oleoyl-CoA of 11-15 microM and displays an optimum activity at pH 7.4. The enzyme activity is reduced approx. 2-fold upon preincubation of microsomes with alkaline phosphatase. Arrhenius plots of ACAT-activity are curvilinear, with curvatures considerably affected by the acclimation temperature of the fish. Carp HMG-CoA reductase has been characterized previously by Teichert and Wodtke ((1987) Biochim. Biophys. Acta 920, 161-170). When measured at 30 degrees C, ACAT activities from 30 degrees C- and 10 degrees C-acclimated carp are identical (approx. 6 pmol/min per mg protein), whilst 'expressed' HMG-CoA reductase activity (18.1 +/- 12.2 pmol/min per mg protein for 30 degrees C-acclimated carp vs. 159.8 +/- 106.6 pmol/min per mg protein for 10 degrees C-acclimated carp) is enhanced 9-fold in the cold environment. This disparity indicates that cold-acclimation results in a massive increase in the capacity for hepatic cholesterol synthesis relative to hepatic cholesterol esterification. At the same time, hepatic compositional analysis reveals identical contents of unesterified cholesterol in either groups of carp but significantly decreased (3-fold) amounts in cholesterol ester (and also in triacylglycerol, 4-fold) in cold-acclimated carp. Moreover, microsomal fractions display lower cholesterol to phospholipid ratios in the cold. In contrast, concentrations of either cholesterol fractions (and of triacylglycerols) in plasma--the mobile compartment for lipoprotein transport--do not differ in cold- and warm-acclimated carp. Based on current concepts of cholesterol metabolism, it is concluded that the cold-enhanced expression of hepatic HMG-CoA reductase activity is a homeostatic response directed against and compensating for a cold-induced but not yet characterized deficiency in hepatic cholesterol availability. PMID- 1450217 TI - Metabolism of intravenously administered 7 alpha-hydroxycholesterol-3 beta stearate in the hamster. AB - In order to investigate the metabolic fate of serum esterified 7 alpha hydroxycholesterol, [4-14C]7 alpha-hydroxycholesterol-3 beta-stearate was synthesized from labeled cholesterol and administered to bile fistula hamsters intravenously. Bile samples were collected at every 20 min for 7 h. Radioactivity was detected in bile 40 min after the beginning of the infusion of the labeled compound and 56.5 +/- 5.7% (48.7-66.0%) of the administered radioactivity was recovered in bile during 7 h. The liver contained appreciable radioactivity (19.5 +/- 7.6% of the administered dose) at the time of sacrifice. Only a trace amount of radioactivity was detected in urine and blood. Cumulative recovery of the radioactivity was 76.3 +/- 8.6% (63.3-90.4%). Major radioactive metabolites in the bile samples were identified to be taurine- and glycine-conjugated cholic acid and chenodeoxycholic acid by radioactive thin-layer chromatographic analysis of the bile samples before and after enzymatic hydrolysis and 3 alpha hydroxysteroid dehydrogenase treatment. The conversion was nearly complete and we could not detect neutral metabolites, such as the mother compound, free 7 alpha hydroxycholesterol and bile alcohols, as well as glucuronidated or sulfated bile acids. It is concluded that serum esterified 7 alpha-hydroxycholesterol could be effectively taken up by the liver, hydrolyzed by cholesterol esterase and metabolized via the normal biosynthetic pathway to taurine- or glycine-conjugated primary bile acids to be excreted into bile. PMID- 1450218 TI - Isolation and characterization of three lysophospholipases from the murine macrophage cell line WEHI 265.1. AB - Anion exchange chromatography of WEHI 265.1 cell homogenates resolved the lysophospholipase activity into three peaks, when assayed using lysophosphatidylcholine as a substrate. Peaks 1 and 2 were purified by sequential hydrophobic interaction and gel filtration chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the purified peaks 1 and 2 indicated homogeneous proteins with apparent masses of 28 and 27 kDa, respectively. Peak 3 lysophospholipases was partially purified by hydrophobic, hydroxyapatite and gel filtration chromatography. Peak 3 lysophospholipase also had calcium-dependent phospholipase A2 activity, which further co-purified with the lysophospholipase activity. The three lysophospholipases were characterized with respect to substrate specificity, additional enzymatic activities and the effects of lipids, metal ions and other compounds on enzymatic activity. Peaks 1, 2 and 3 hydrolyzed lysophosphatidylcholine most readily, but lysophosphatidylethanolamine also served as substrate for each enzyme. Furthermore, all three enzymes hydrolyzed platelet activating factor and acetylated lysophosphatidylcholine. Each lysophospholipase was inhibited by free fatty acids and by palmitoyl carnitine, although the relative sensitivities to these agents differed among the enzymes. The lysophospholipase activities of peaks 1 and 2, but not peak 3, were inhibited by phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate and N ethylmaleimide. Although they had similar masses, the amino acid compositions of peaks 1 and 2 differed, indicating that these are distinct proteins rather than posttranslational modifications of the same gene product. PMID- 1450219 TI - Elevated glucose alters A23187-induced release of arachidonic acid from porcine aortic endothelial cells by enhancing reacylation. AB - Cultured porcine aortic endothelial cells were conditioned in normal (5.2 mM) and elevated (15.6 mM) glucose, prelabeled with [14C]arachidonic acid and stimulated with ionophore A23187. Elevated glucose cultures released less radiolabeled products and less [14C]arachidonic acid. Analysis of cellular lipids revealed that elevated glucose reduced net loss of radiolabel from diacylphosphatidylethanolamine, did not affect early phosphatidylinositol hydrolysis, and increased net loss from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine. Uptake of radiolabel upon stimulation was examined to measure the role of reacylation on the diminished net release of radiolabel in elevated glucose cultures. Enhanced acylation of [3H]arachidonic acid into cellular lipids, especially PI, was observed in stimulated and resting cultures with elevated glucose. Further, pretreatment of the cultures with an acyltransferase inhibitor, thimerosal, prior to A23187 stimulation in radiolabeled cultures, abolished the effects of glucose on eicosanoid and arachidonic acid release. Differences in the ionophore-induced net loss of radiolabel from diacylphosphatidylethanolamine and phosphatidylinositol of the two glucose treatments were diminished by thimerosal exposure, while net loss of radiolabel from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine were unaffected. The data indicate that elevated glucose alters deacylation and enhances reacylation of arachidonic acid into endothelial cells and particularly into phosphatidylinositol. Enhanced reacylation may explain some of the altered lipid pathways that have been observed in experiments that elevate glucose concentrations or involve diabetes. PMID- 1450220 TI - Is there still a role for radioisotope techniques in pulmonary embolism? PMID- 1450221 TI - The use of exercise technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc Sestamibi) perfusion scanning in the detection of acute rejection after cardiac transplantation. AB - Acute cardiac rejection remains an important cause of death during the first year following cardiac transplantation. Right ventricular biopsies at regular intervals are the main method of detecting rejection, although it is invasive. Unfortunately, non-invasive methods of detecting rejection have not proved reliable enough to replace cardiac biopsies. We assessed the usefulness of technetium-99m 2-methoxy-isobutyl-isonitrile (99mTc-Sestamibi) perfusion scanning in detecting acute rejection in 12 human orthotopic cardiac transplant recipients. Rest and exercise studies and right ventricular biopsies were performed on two occasions. Isotopic evidence of rejection was defined as a perfusion abnormality on either the resting or exercise studies. 99mTc-Sestamibi studies successfully identified acute rejection in 8 of 11 rejection episodes (p less than 0.04). The calculated sensitivity and specificity of 99mTc-Sestamibi scanning were both 72%. Perfusion scanning with 99mTc-Sestamibi may be useful in the diagnosis of acute rejection in cardiac transplant recipients. PMID- 1450222 TI - Changes in serum testosterone levels after myocardial infarction. AB - To evaluate the effect of a severe non-endocrine disease on testosterone levels we determined the total testosterone (T), free testosterone (fT), myoglobin and myosin plasmatic levels in 18 men at the time of hospitalization for acute myocardial infarction (AMI), and 1, 3, 7 and 21 days later. Five different methods for determining fT were applied and compared; 1) radioimmunoassay after ultrafiltration, 2) direct analogue based radioimmunoassay (RIA), 3) calculation from total T, sex-hormone-binding globulin (SHBG) and albumin concentrations, 4) calculation from total T, SHBG concentrations with albuminemia fixed at 40 g/L, and 5) evaluation by the (total T)/(SHBG) ratio (fT index). After AMI the total T and fT decreased rapidly (minimum at day 1) and then increased until day 21. While a lower sensitivity in detecting small changes was noted for the direct analogue based fT RIA and for the calculation using a fixed albuminemia, the evolving pattern of the 5 different fT determinations was similar despite different absolute values. However, there was a wide scattering in the results from the different methods used to determine fT. Compared to ultrafiltration, the fT values were lower by direct analogue based assay and higher by calculation. There was a trend of correlation between changes in total T and the maximum myosin concentration (r = 0.557, p = 0.02), showing a relationship between the hormonal changes and the severity of the myocardial infarction. PMID- 1450223 TI - A modeling analysis of rest-stress and stress-rest injection sequences in performing thallium-201 myocardial perfusion scintigraphy. AB - A new thallium-201 stress testing protocol is proposed in which rest images are obtained prior to stress images. The advantages of the new protocol are that it saves time and requires no special diet or activity restriction between imaging sets. A potential problem from reversing the standard imaging sequence is decreased sensitivity to stress perfusion defects owing to background counts from the rest image. Using a cardiac phantom, 74 sets of stress and rest images were simulated under the new protocol and the standard stress-redistribution reinjection protocol. Seven observers were asked to classify the images as normal or abnormal and to distinguish ischemic from fixed defects. Differences in observer performances between the two protocols were compared. With the new protocol, observers had sensitivities of 75%-90% and specificities of 100% in identifying a perfusion defect on the stress study. Accuracy was improved if the image counts from the rest study contributed less than 40% of the final counts of the stress study. Detection of ischemic and fixed defects was as good as or better than with standard protocols. Based on the phantom model, rest followed immediately by stress imaging sequence is an advantageous alternative for thallium-201 stress testing. Clinical trials are necessary to further evaluate this new protocol. PMID- 1450224 TI - Long-term biodistribution in tumored mice of murine and chimeric B72.3-IgG antibody radiolabeled with 114mIn via both DTPA and a macrocyclic chelator. AB - To assess the possibilities of using 114mIn as a therapeutic agent, the long-term biodistribution of 114mIn was studied, in tumor-bearing nude mice, after injection of labeled monoclonal antibody (MoAb) B72.3 IgG, either DTPA-coupled murine, DTPA-coupled chimeric, or macrocycle-coupled chimeric antibody. Although the biodistributions in all cases were similar, there were important differences. The use of DTPA-coupled chimeric antibody led to higher concentrations of radioactivity in tumor, and to lower concentrations in liver and bone, as compared to DTPA-coupled murine antibody. The use of macrocycle-coupled chimeric antibody led to higher concentrations of radioactivity in the liver and in bone as compared to the DTPA-coupled chimeric antibody. However, in this case there were no significant differences in tumor uptake or clearance. Radiation doses were calculated based on the organ retention and by neglecting source-to-target contributions. Radiation dose distribution was marginally favorable for therapy in the group injected with DTPA-coupled chimeric antibody. PMID- 1450225 TI - Evaluation of alkylated derivatives of 99mTc-propylene amine oxime (99mTc-PnAO). AB - Several lipophilic di-alkylated derivatives of propylene amine oxime (PnAO were complexed to 99mTc. Assessment of the 99mTc-PnAO derivatives included biodistribution and qualitative autoradiography. All of the derivatives studied penetrated the intact blood-brain-barrier, with the 99mTc-dibutyl-PnAO complex exhibiting the lowest initial brain uptake while the 99mTc-diethyl-PnAO and the 99mTc-dipropyl-PnAO complexes possessing nearly identical initial brain uptake as compared to 99mTcPnAO. Qualitative autoradiographs revealed significant loss of image resolution with extended time post injection indicative of rapid radiopharmaceutical washout. Although increasing alkyl chain length did not enhance initial brain uptake, the data demonstrates that limited modification of the PnAO ligand structure can be performed without decreasing cerebral uptake of the respective 99mTc complex. PMID- 1450226 TI - Single determination of CA 15.3 and bone scintigraphy in the diagnosis of skeletal metastases of breast cancer. AB - Single determination of CA 15.3 and bone scintigraphy were performed on the same day as follow-up procedures in 864 patients with breast cancer. The sensitivity and specificity of bone scintigraphy for skeletal metastases were 99% and 88.8%, respectively. The overall sensitivity and specificity of CA 15.3 (cut-off for pathological values greater than 30 U/mL) for cancer recurrence or distant metastases were 69.2% and 92.1%, respectively. The sensitivity of CA 15.3 for bone metastases was lower (69.4%) than that of bone scintigraphy. This was mainly due to the relatively high proportion of false-negative CA 15.3 levels in patients with 1-2 bone metastases (sensitivity = 33.3%). According to this result, the circulating levels of CA 15.3 showed a good correlation with tumor extension and, in patients with bone metastases, with the number of skeletal lesions. As regards the contribution of CA 15.3 to the diagnosis of bone metastases, the demonstration of elevated CA 15.3 values in patients with positive bone scintigraphy could support the diagnosis of skeletal metastases. In fact, the positive predictive value of CA 15.3 in patients with positive bone scintigraphy was significantly higher than with only bone scintigraphy (53.8%) or CA 15.3 (50.4%). Finally, very high values of CA 15.3 in patients with known bone metastases could indicate the presence of visceral metastases (mean CA 15.3 in patients with bone metastases = 125.8 U/mL; mean CA 15.3 in patients with bone and visceral metastases = 420.5 U/mL). PMID- 1450227 TI - Conditions for labeling of Schistosoma mansoni cercaria with technetium-99m. AB - Study of the labeling of Schistosoma mansoni cercaria with technetium-99m (99mTc) at room temperature (25 degrees C) and 37 degrees C shows that the incorporation of radioactivity in this cercaria increases with the increase in stannous chloride concentration, reaching a constant value threshold at 130.00 microM. Strong binding of the 99mTc was obtained since the radioactivity was not washed out. The characteristic motion of the cercaria, labeled at 25 degrees C and 37 degrees C, was only modified at the concentration of 1300 microM for both temperatures, showing that the methodology here described can be applied to living structures. With this technique it is possible to obtain a cercariae suspension labeled with a radionuclide that is very inexpensive and readily available. Furthermore, it is a gamma emitter with a photon energy of 140 keV that would permit one to make scannings of the infected animals and causes less of an environmental impact and present fewer radioactive disposal problems than the long lived radionuclides. PMID- 1450228 TI - Radioiodinated azomycin pyranoside (IAZP): a novel non-invasive marker for the assessment of tumor hypoxia. AB - 1-(4-Iodo-4-deoxy-beta-L-xylopyranosyl)-2-nitroimidazole (Iodoazomycin Pyranoside; IAZP) was synthesized, labelled with radioiodine(123I, 125I) and evaluated for non-invasive assessment of tumor hypoxia. A biodistribution study with Balb/c mice bearing EMT-6 tumors showed a tumor-to-blood ratio of 13.9, representing 0.5 percent of injected dose per gram of tissue, at 24 hours post injection. This ratio is the highest for any 2-nitro-imidazole reported to date in this tumor model. Rapid elimination of radioactivity from the whole-body was noted (greater than 97% in 24 hours) and thyroid radioactivity at 24 hours was much lower than with other analogues of this series. No toxicity was observed in Balb/c mice at a dose 100 times higher than the anticipated human dose required for scintigraphic imaging. Planar, whole-body gamma scintigraphic images in the murine Balb/c EMT-6 tumor model clearly delineated tumor tissue at 24 hours post injection. These observations suggest that IAZP may be a suitable agent for non invasive, clinical assessment of tumor hypoxia. PMID- 1450229 TI - Pharmacokinetics of indium-111 labeled 10-3D2 antibreast-tumor antibody in patients. AB - In a program to investigate patient pharmacokinetics of labeled anti-tumor antibodies, a study of the 10-3D2 anti-breast tumor antibody was conducted. The F(ab')2 fragment, coupled with DTPA, was radiolabeled with indium-111 and 1 mg (37 MBq, or 1 mCi) administered to each of 7 patients with documented or suspected breast carcinoma. Abnormal accumulations of radioactivity were observed in only one patient even though 5 had evidence of disease at the time of imaging. Despite the reported absence of circulating antigen to this antibody, sera from one patient showed evidence of a high molecular weight immune complex by size exclusion HPLC. However, this patient had detectable circulating HAMA, which cannot be excluded as the cause of such immune complex. Urine excretion of radioactivity varied greatly from patient to patient (from 2-34% ID within the first day) but the mean value (0.22% ID/hour) was equal to that seen by us in previous studies. The biodistribution of the label was found to be unusual in that kidney levels increased in all patients during the first day and, in particular, liver radioactivity levels decreased in all patients. PMID- 1450230 TI - Risk stratification after myocardial infarction. PMID- 1450231 TI - SPECT: current and future developments. PMID- 1450232 TI - Myocardial salvage in reperfusion injury. PMID- 1450233 TI - Viable myocardium: when to search for it? PMID- 1450234 TI - Positron emission tomography versus thallium-201 scintigraphy for assessment of viable myocardium. PMID- 1450235 TI - Combined evaluation of perfusion and function for the identification of viable myocardium. PMID- 1450236 TI - 99mTc-sestamibi: is it a tracer of variability. PMID- 1450237 TI - Interpretational criteria for positive and negative antimyosin scan in the diagnosis of myocarditis. PMID- 1450238 TI - Thallium-201 reinjection: truth or artifact? PMID- 1450239 TI - Advances in myocardial perfusion imaging: 99mTc-teboroxime. PMID- 1450240 TI - Biodistribution in humans and preliminary clinical evaluation of a new tracer with optimized properties for myocardial perfusion imaging: [99mTc]Q12. PMID- 1450241 TI - The role of nuclear cardiology in the evaluation of coronary artery disease. PMID- 1450242 TI - Biological and methodological problems in using radiolabelled monoclonal antibodies in cardiology. PMID- 1450243 TI - Application of monoclonal antibodies in cardiovascular diseases: atherosclerosis and pulmonary emboli imaging. PMID- 1450244 TI - Quantitation of regional myocardial blood flow in coronary microvascular disease. PMID- 1450245 TI - Thallium-201: single injection, reinjection or twenty-four hour delayed imaging? PMID- 1450246 TI - Monitoring rejection in heart transplant recipients: the Temple University experience. PMID- 1450247 TI - Indium-111 antimyosin antibodies for detection of rejection and drug induced cardiomyopathies. PMID- 1450248 TI - The heart transplant as a clinical model to assess viable myocardium by radioactive tracers. PMID- 1450249 TI - Screening of high risk patients with thallium-201 myocardial perfusion imaging. PMID- 1450250 TI - Adenosine and dipyridamole myocardial scintigraphy. PMID- 1450251 TI - Continuous monitoring of ventricular function. PMID- 1450252 TI - Radionuclide methods for the evaluation of the efficacy of thrombolytic therapy in acute myocardial infarction. PMID- 1450253 TI - Italian multicenter reinjection trial (SIRT): preliminary results of thallium-201 segmental analysis. PMID- 1450254 TI - Scintigraphic assessment of the results of myocardial revascularization. PMID- 1450255 TI - [Mycosis in the 1990's]. PMID- 1450256 TI - [Comparative activities of ciprofloxacin, amoxicillin, and cotrimoxazole in an experimental model of enteritis caused by Salmonella non typhi]. AB - With the use of an in vitro experimental model of enteritis by Salmonella non typhi the efficacy of amoxicillin, cotrimoxazole and ciprofloxacin in the eradication of this fecal pathogen and the prevention of bacteremia was evaluated. Following a fasting period of 48 hours a total of 160 rats were administered 10 UFC of 2 strains of Salmonella non typhi via intragastric tubing. One of the strains was sensitive to amoxycillin and cotrimoxazole (60 rats) and the other strain was resistant to both but was sensitive to ciprofloxacin (100 rats). The antimicrobials were administered 24 hours after the bacterial infection in daily doses for 5 consecutive days. According to the results obtained amoxicillin and cotrimoxazole were ineffective in the eradication of the fecal pathogen indicating an important obstacle in the appearance of bacteremias. To the contrary, ciprofloxacin, even at low doses, eliminated the microorganisms early and demonstrated high efficacy in the prevention of bacteremia in the animals when these results were compared with those of the untreated group. PMID- 1450257 TI - [Escherichia coli virulence factors causing peritonitis, appendicitis and other extraintestinal infections]. AB - Fifty-nine E. coli strains isolated from clinical cases of peritonitis, appendicitis, cholecystitis, wounds and respiratory infections as well as from other miscellaneous sources were investigated. A control group constituted by 475 E. coli strains isolated from the faeces of healthy individuals were also studied. E. coli O-grouped and investigated for production of cytotoxic necrotizing factor CNF1 and alpha-haemolysin (Hly), expression of P fimbriae and mannose-resistant (MRHA) and mannose-sensitive (MSHA) haemagglutination. Virulence factors significantly associated with extraintestinal strains were: production of CNF1 (19% versus 5%, p < 0.001), Hly (27% versus 9%; p < 0.001) and expression of MRHA (44% versus 16%; p < 0.001). The majority of extraintestinal strains (68% versus 36%; p < 0.001), in contrast with faecal E. coli, belonged to O serogroups frequently detected in uropathogenic and bacteraemic E. coli. These results suggest that E. coli causing different types of extraintestinal infections show similar virulence factors and belong to the same serogroups. However, between E. coli isolated from intraabdominal, wound and respiratory infections the number of strains with virulence factors was lower than in E. coli causing urinary tract infections and sepsis. PMID- 1450258 TI - [HIV infection in an autonomous Spanish community (La Rioja). Features, trends and conclusions applicable to other regions]. AB - BACKGROUND: The epidemiologic characteristics of HIV infection in La Rioja (Spain) were studied and the future tendencies of the same analyzed. METHODS: The data from official Health sources were collected and analyzed. RESULTS: In La Rioja, the 5th region in Spain regarding to AIDS incidence, the duplication time of the number of cases continues to shorten. The number in December 1991 was 81. The heterosexual route of infection was 5% of the cases of AIDS up to December 1990 and in 1991 it was 15%, while, with regards to the total number of seropositive subjects, the number rose from 0.3% in December 1990 to 10% in 1991. One thousand one hundred fifty-one seropositive patients were detected in December 1991 representing seroprevalence of 0.34% which reaches 1.14% in the age range between 18-32 years. Mean hospital stay was 23.6 days with 3,032 hospital stays calculated for 1991 representing 8.3 occupied beds/day. There are presently 92 patients undergoing antiviral treatment. Between 43-69 new cases of AIDS have been calculated for 1992. CONCLUSIONS: 1) Medical care should be provided to a greater number of seropositive people to avoid early deterioration. 2) The increase in heterosexual infection is alarming. 3) The need for rehabilitation centers for drug abusers and social alternatives to prostitution is clear. 4) Organized campaigns pointing out and returning the dignity and value of life and therewith the role of human sexuality are needed. 5) Alternative means to conventional hospitalization is required. PMID- 1450259 TI - [Outbreak of Legionnaires' disease in a private apartment building]. AB - BACKGROUND: An outbreak of legionnaires disease occurred in Zaragoza (Spain) in an uncommon environment such as a private apartment building was studied. METHODS: The investigation began upon notification of 3 patients admitted with pneumonia, living in the same apartment building. The suggestion of a common source of infection led to an active search for cases and a micro-environmental study of the zone where the patients lived, as well as a follow up study of other cases with hospital acquired pneumonia throughout the city. RESULTS: Six cases were detected over 9 days with a rate of 1.54%. The evolution of all the cases was favorable. The causal agent was serologically identified as Legionella pneumophilia serogroup 1 which was also found in the shower of one of the patient's bath with further confirmation that the strain isolated belonged to the Pontiac subgroup. CONCLUSIONS: The probable source of infection was the potable water. The stagnation, low temperature of the boiler and the under-chlorination of the water are factors which may have contributed to the appearance of this outbreak. The control of this type of outbreak must be based on a specific information system which treats this disease as requiring individualized declaration. PMID- 1450260 TI - [Evaluation of a selective medium for the isolation of Moraxella catarrhalis]. AB - The recovery rate of Moraxella catarrhalis in a selective culture medium with acetazolamide and in a conventional blood-agar medium was compared from 1291 samples from the respiratory tract and conjunctivae of children and adults with respiratory and ocular symptomatology. M. catarrhalis was recovered in 215 samples on the acetazolamide medium, and only. 18 cases in the blood agar medium (p < 0.001). The highest recovery of M. catarrhalis was in samples with an accompanying flora, either pathogenic or commensal, such as pharyngeal and nasal exudates. The prevalence of M. catarrhalis in adults and children was 2% and 28%, respectively. We therefore, recommend the use of the acetazolamide medium for the recovery of M. catarrhalis in samples where M. catarrhalis is expected to be present with an accompanying flora. PMID- 1450261 TI - [Isolation of Mycobacterium tuberculosis with primary resistance to chemotherapeutic agents in patients with HIV infection]. AB - BACKGROUND: To evaluate the resistance of Mycobacterium tuberculosis in subjects with simultaneous infection by the human immunodeficiency virus. METHODS: Isolation of Mycobacterium tuberculosis was carried out in a University hospital over a period of 7 years with selection of those corresponding to subjects with HIV infection. The isolation of Mycobacterium tuberculosis with resistance to one or more chemotherapeutic drugs was identified and is described herein. RESULTS: A total of 287 subjects were identified having tuberculous disease, 39 (13.59%) of them presented a simultaneous infection by the human immunodeficiency virus. In 4 of the latter (10.26%) Mycobacterium tuberculosis resistant to one or more chemotherapeutic drugs was isolated with the most frequent resistance being to isoniazide (3/4). CONCLUSIONS: A high degree of diagnostic suspicion must be maintained in patients with the human immunodeficiency virus with respect to tuberculosis, not only because of frequent endogenous activation but also because of the danger of in-hospital transmission. The possibility of resistance makes systematic antibiograms in these cases advisable. In these patients recommendations regarding treatment should be followed avoiding shortened or simplified therapeutic periods which have occasionally been demonstrated as ineffective. PMID- 1450262 TI - [Blastocystis hominis]. PMID- 1450263 TI - [Fever, eosinophilia, and subcutaneous nodules. Onchocerciasis. Onchocerca volvulus (river-blindness)]. PMID- 1450264 TI - [Osteomyelitis from a cat bite]. PMID- 1450265 TI - [Acromioclavicular arthritis of the right shoulder with acute presentation]. PMID- 1450266 TI - [Strongyloidiasis in a patient with acquired immunodeficiency syndrome]. PMID- 1450267 TI - [Outbreak of food poisoning caused by Salmonella enteritidis phagotype 6 occurring in Tenerife]. PMID- 1450268 TI - [Pulmonary infection caused by Mycobacterium szulgai in a patient with hairy-cell leukemia]. PMID- 1450269 TI - [Bacteremia caused by Shigella flexneri]. PMID- 1450270 TI - [Disseminated infection caused by Mycobacterium kansasii in acquired immunodeficiency syndrome]. PMID- 1450271 TI - [Vibrio alginolyticus in clinical specimens]. PMID- 1450272 TI - [Wound infection caused by Pasteurella dagmatis following a cat scratch]. PMID- 1450273 TI - It happens all over the world.... PMID- 1450274 TI - Rick-A-Nator appliance. PMID- 1450275 TI - Case report: non-surgical Class III. PMID- 1450276 TI - Ready for phase II--quantitative radionuclide bone scanning. PMID- 1450277 TI - Defend yourself against faulty appliances! PMID- 1450278 TI - Abnormal dento-facial growth--long face syndrome. PMID- 1450279 TI - Case report: correction of Class II skeletal. PMID- 1450280 TI - Case report: Class III skeletal, prognathic MD; orthognathic MX. PMID- 1450281 TI - Muscle deprogramming splint. PMID- 1450282 TI - The diagnostic importance of the Payne technique. PMID- 1450283 TI - Case report: tip-edge treatment of a Class II, division 1 malocclusion with an anterior openbite. PMID- 1450284 TI - Case report: Rick-a-Nator. PMID- 1450285 TI - Universal lingual arch wire: combination appliance for orthopedics and orthodontics. PMID- 1450286 TI - Physical aspects of the EEG in schizophrenics. AB - Physical and dynamic aspects of the electroencephalogram (EEG) were evaluated in 12 schizophrenic patients and 12 matched healthy control subjects by means of two descriptive measures proposed by Hjorth (complexity and mobility) and by a nonlinear measure, dimensional complexity. These measures were compared to power spectra analyses. EEG was recorded from frontal, central, and parietal leads under resting conditions (eyes open and eyes closed) for 12 epochs each of 25 sec. Patients showed the expected increased activity in the 1-7 Hz band and, furthermore, a scalp distribution of dimensional complexity and Hjorth complexity opposite to the distribution in controls: in patients dimensional complexity yielded higher values at frontal (Fz) than central (Cz) leads, whereas the resemblance to sinusoidal waveshape (Hjorth complexity) was larger at Fz than Cz. Results indicate more dynamic complexity or variables determining the dynamics of brain processes in frontal areas in patients. PMID- 1450288 TI - Shifts in covert visual attention in schizophrenic patients and normal controls. PMID- 1450287 TI - Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. AB - Diminished gating of the P50 auditory evoked response to repeated stimuli is a psychophysiological feature of schizophrenia, that is also present in many relatives of patients. Animal models of auditory sensory gating indicate that nicotinic cholinergic neurotransmission is a critical neuronal substrate. The aim of this experiment was to determine if the deficit in sensory gating could be reversed by nicotine administration. Nonsmoking relatives of schizophrenics with abnormal sensory gating were selected as subjects for this initial double-blind trial, to avoid effects of psychotropic medications that might complicate trials in schizophrenic patients themselves. Nicotine-containing gum increased P50 sensory gating to near normal levels within 30 min of administration. The effect was transient; the gating of P50 returned to baseline levels within 1 hr. There was no change observed after placebo administration. In one of the subjects, the anticholinesterase inhibitor physostigmine similarly normalized P50 gating. The results are consistent with the hypothesis that nicotinic cholinergic neurotransmission may mediate a familial psychophysiological deficit in schizophrenia. PMID- 1450289 TI - A 31phosphorous magnetic resonance spectroscopy study of diazepam does not affect brain phosphorous metabolism. PMID- 1450290 TI - Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome. AB - Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive dysfunction. Because glucocorticoid excess is associated with hippocampal damage in animals, and the hippocampus participates in learning and memory, we explored the relationships between hippocampal formation (HF) volume, memory dysfunction, and cortisol levels in 12 patients with CS. After magnetic resonance imaging, HF volume was determined using digital sum of track ball traces of dentate gyrus, hippocampus proper and subiculum, correcting for total intracranial volume. For 27% of the patients, HF volume fell outside the 95% confidence intervals for normal subject volume given in the literature. In addition, there were significant and specific correlations between HF volume and scores for verbal paired associate learning, verbal recall, and verbal recall corrected for full-scale IQ (r = 0.57 to 0.70, p < 0.05). HF volume was negatively correlated with plasma cortisol levels (r = -0.73, p < 0.05). These studies suggest an association between reduced HF volume, memory dysfunction, and elevated cortisol in patients with CS. PMID- 1450291 TI - Continuous physiological changes and subjective reports in panic patients: a preliminary methodological report. AB - Six panic disorder patients and six matched control subjects were studied using a new technique allowing continuous and simultaneous monitoring of physiological responses (blood pressure, heart rate, respiration) and subjective reports of anxiety and panic. This was done before, during, and after CO2 inhalation. Panic patients had significantly higher variability in their heart rate, blood pressure, and breathing rate than the control subjects. They also had irregular breathing patterns with frequent pauses. We identified three different patterns of response to CO2 inhalation in the panic patients. Some patients who panicked on CO2 showed a definite association between changes in physiological responses that preceded their subjective ratings of anxiety; however, others did not show this pattern. The possibility of different physiological mechanisms of panic in different patients is discussed. PMID- 1450292 TI - Cardiovascular phase relationships to the cortical event-related potential of schizophrenic, depressed, and normal subjects. AB - Cardiovascular phase, especially diastole, influences attention and the event related potential (ERP) of the right hemisphere of the brain. Depression and schizophrenia are characterized by attentional deficits, unique lateralization of brain function, and deviant phase relationships of biological oscillators. In the present study, the ERP was recorded during stimulation triggered by diastole and systole in control (n = 16), depressed (n = 16), and schizophrenic (n = 9) subjects. Fifty tones were presented and subjects were instructed to count them silently. Previous findings were supported of delayed latencies and increased amplitude in depressed patients and decreased amplitudes and delayed latencies in schizophrenics. An exaggerated effect of diastole on the ERP in the right hemisphere was observed in depressed patients, however, no cardiovascular effect on the ERP was apparent in schizophrenic patients. Results suggested that heart/brain networks are tightly coupled in normal controls, perhaps "overdriven" in depressed patients, and uncoupled in schizophrenics. PMID- 1450293 TI - Language comprehension in schizophrenics and their brothers. AB - Disturbances in language functioning may be associated with familial vulnerability to schizophrenia. Language comprehension, measured by the Luria Nebraska Relational Concepts Factor Scale, was evaluated in 36 schizophrenic probands and their nonschizophrenic adult brothers (n = 41), and in 18 normal controls. Language comprehension performance was a function of psychiatric diagnosis in the brothers. Brothers who met criteria for schizophrenia-spectrum disorders showed significantly reduced language performance compared with unaffected brothers and normal controls. Moreover, abnormal language performance was exhibited by significantly more probands and spectrum-disordered brothers than by the normal controls and the brothers without schizophrenia-spectrum disorders. Finally, language performance was not significantly different for 31 pairs of schizophrenic probands and their brothers. Impaired language comprehension appeared comparatively specific in this sample of relatives, as groups were not significantly different on measures of nonlinguistic concept formation (Wisconsin Card Sorting Test) and general intellectual functioning (WAIS-R Information and Block design). Results suggest that impaired language comprehension is associated with familial vulnerability to schizophrenia, and that this disturbance may be most severe in relatives diagnosed with schizophrenia-spectrum disorders. PMID- 1450294 TI - The prevalence of autoantibodies among right and left handed schizophrenic patients and control subjects. AB - Sera from schizophrenic patients (n = 186) and healthy control subjects (n = 346) were tested for the presence of seven common autoantibodies by standard immunological methods. The association between handedness and autoantibodies was tested in a multi-way contingency table using a log-linear model. For men, but not women, nondextrals (patients and controls) were twice as likely to test positive for autoantibodies than dextrals (p = 0.0002). Although more women (33%) than men (24%) tested positive for autoantibodies, handedness was not a distinguishing factor among women. These data suggest that sinistrality and gender are associated with autoantibodies in a subgroup of schizophrenic patients and healthy control subjects. PMID- 1450295 TI - Hypothalamic-pituitary-adrenal axis function and suicidal behavior in depression. AB - Hypothalamic-pituitary-adrenal (HPA) axis function was examined in relation to suicidal behavior in depression. There were no significant differences between depressed patients who had or had not attempted suicide for either cerebrospinal fluid concentrations of corticotropin-releasing hormone, plasma cortisol levels predexamethasone or postdexamethasone, or for urinary-free cortisol outputs. However, depressed patients who had made a violent suicide attempt had significantly higher 4 PM and maximum postdexamethasone plasma cortisol levels, and significantly more of them were cortisol nonsuppressors than patients who had made nonviolent suicide attempts. A 5-year follow-up was carried out. There were no significant differences on indices of HPA function between depressed patients who did or did not reattempt suicide during the follow-up or who had never attempted suicide. These results suggest the possibility that dysregulation of the HPA axis may be a determinant of violent suicidal behavior in depression. PMID- 1450296 TI - Preliminary studies of 6 beta-hydroxydexamethasone and its importance in the DST. AB - The role of the metabolites of dexamethasone (DEX) in the dexamethasone suppression test (DST) has never been fully elucidated. We report here our preliminary studies of 6 beta-hydroxydexamethasone (6 OH-Dex), a known metabolite of DEX, on the hypothalamic-pituitary-adrenal (HPA) axis of the rat; its activity in the most commonly used radioimmunoassay for plasma DEX; and its plasma concentrations in a normal human subject during the standard 1.0 mg DST. Six OH Dex administered subcutaneously to rats at a dose of 1 mg/kg was able to completely suppress corticosterone production for at least 3 hr. In the IgG Corp. radioimmunoassay for plasma DEX, 6 OH-Dex was moderately cross-reactive yielding a 50% cross-reactivity of 10%. Gas chromatographic coupled mass spectroscopic analysis of human plasma samples, obtained 12 to 20 hr after the oral ingestion of 1.0 mg DEX, demonstrated similar plasma concentrations for both the parent compound and the 6-hydroxyl metabolite. The relevance of these findings, particularly to pharmacokinetic studies of the DST, is discussed. PMID- 1450297 TI - Bupropion treatment of fluoxetine-resistant chronic fatigue syndrome. AB - Chronic fatigue syndrome (CFS) includes many symptoms of major depression. For this reason, many antidepressants have been used to treat the symptoms of this disorder. Among the more recently released antidepressants are fluoxetine and bupropion. In this open study, nine CFS patients who either could not tolerate or did not respond to fluoxetine showed significant response when administered 300 mg/day of bupropion for an 8-week period in both rating of HDRS (t = 4.80, p < 0.01) and BDI (t = 2.48, p < 0.05). Furthermore, bupropion improvement in Hamilton Depression Rating Scale correlated significantly with change in plasma homovanillic acid (HVA) (r = 0.96, p < 0.01). Plasma total methylhydroxyphenolglycol (MHPG) also increased significantly during bupropion treatment (t = 2.37, p = 0.05). Measures of T1 microsomal antibodies also decreased over treatment time; increases in natural killer cell numbers correlated inversely with change in plasma levels of free MHPG (r = -0.88, p < 0.05). Bupropion responders were more likely to have trough blood levels above 30 ng/ml (chi 2 = 3.6, p = 0.05). PMID- 1450298 TI - Stimulus parameter effects on the P50 evoked response. PMID- 1450299 TI - Counter clockwise scalp hair whorl in schizophrenia. PMID- 1450300 TI - [The value of 2- and 3-dimensional computed tomography in the diagnosis and classification of midfacial and orbital fractures]. AB - The value of 2D- and 3D-computed assisted tomography in detecting and classifying midfacial fractures and craniofacial deformities acquired by gunshot injuries was assessed in 123 resp. 26 patients and compared with the postoperative results. In a comparative study 37 patients were prospectively examined by pluridirectional tomography. Examinations of a macerated skull were performed to optimize 3D investigation technique. High resolution CT proved to be the most reliable technique in detecting midfacial fractures and associated soft tissue injuries. 3D-imaging of bony surfaces allowed clear demonstration of fraction extent and fragment displacement without offering additional detail information. 3D-based computer-assisted manufacturing of individual models facilitated surgical planning of complex midfacial injuries. PMID- 1450301 TI - [Initial experience with digital luminescence radiography in the radiological diagnosis of the visceral cranium]. AB - The purpose of this study was the evaluation of digital luminescence radiography (PCR; Philips Computed Radiography) used in routine radiological analysis of the facial skull. Besides the standard radiographs additional PCR shots were taken in 16 cases. The subjective evaluation was carried out by three different people using clinical criteria. PCR films showed a significant advantage compared to standard radiographs for the above mentioned applications. PMID- 1450302 TI - [The complication incidence after surgical treatments of mouth, jaw and facial tumors in patients over 70]. AB - After operative therapy of tumors of mouth, jaws and face by patients older 70 years the frequency of complications were 26%. Local and systemic disturbances had nearly similar frequencies. Preexistent diseases, therapeutic concepts and methods of anaesthesia influenced as well frequencies of complications as postoperative lethality. In the analysed group of elderly patients the lethality was unexpected low (2,4%). PMID- 1450303 TI - [Laser-induced photoacoustic effects in the dentin]. AB - To study photoacoustic effects in dentin caused by UV-laser ablation, laser induced shockwaves were measured using piezoelectric PVDF films. Above the tissue specific energy threshold for photoablation the amplitude of the acoustic shock waves is proportional to the applied laser energy density. Laser energy densities of 2 J/cm2 cause pressure amplitudes of 50 bar, densities of 20 J/cm2 cause pressure amplitudes of 1000 bar. To avoid microcracks in dentine the maximum laser energy density to prepare dentin should be limited to approximately 20 J/cm2. PMID- 1450304 TI - [Light microscopic studies of pulp morphology following orthodontic therapy]. AB - The authors studied the dental pulp morphology and distribution of acid and neutral mucopolysaccharides in teeth subjected to orthodontic therapy. The teeth were moved with a fixed appliance using forces of 60-200 g. Changes in the histological structure of the dental pulp followed the therapy. The number of collagen fibres increased; they were densely packed and formed thick bundles. A certain degree of hyalinization was also observed. The dental pulp cavity was narrowed by apposition of hard tissue deposits along the canal wall. Pulp stones and diffuse calcification were often encountered. The reaction of acid mucopolysaccharides was found to be very weak, sometimes even negative. The reaction of neutral mucopolysaccharides was not affected so markedly. The results of the paper suggest that changes induced in the dental pulp with fixed orthodontic appliances are irreversible and correspond to those of aging. These premature changes together with rapid hard tissue formation, may negatively influence endodontic treatment in the future. PMID- 1450305 TI - [The assessment of the caries risk in young adults]. AB - Several factors for caries prediction have been proved in a one-year follow-up study on 73 patients. The white-spot lesions have proved to be a good criteria for caries prediction in this population. These lesions could be combined with the microbiological tests Dentocult SM and Oricult N or with the determination of the buffer capacity (Dentobuff), which did not much improve the prediction. PMID- 1450306 TI - [Chronic pain]. PMID- 1450307 TI - [Backache and the anesthetist]. PMID- 1450308 TI - [Monitoring perfusion with transcranial Doppler ultrasound. Progress in cerebral monitoring?]. PMID- 1450309 TI - [Clinical comparison of various infusion regimens within the scope of postoperative on demand analgesia with fentanyl]. AB - 80 patients (ASA I-III, mean age 40-50 years, mean weight 59-68 kg) recovering from major gynaecological surgery (170-200 min) under balanced anaesthesia were randomly assigned to four groups to self-administer intravenous fentanyl during the early postoperative period. PCA devices were ODAC and Prominject with fentanyl demand doses of 34.5 or 34 micrograms, respectively, and lockout times of 1 or 5 min. Concurrent fentanyl infusion was none (group Prom), fixed-rate with 4 micrograms/h (group ODACf), tail-dose, i.e., a fixed-rate infusion with 17 mg/h for a maximum of 60 minutes following a valid demand (group Prom(t)), or adaptive, starting with 4 micrograms/h and being adapted to individual needs depending on total fentanyl consumption in the latest 60-minute period (group ODACa). Data were collected for fentanyl consumption, venous fentanyl serum concentrations in fixed intervals, actual and retrospective verbal rating pain scores (0-5), haemodynamic variables, respiratory rate, side effects and patients' acceptance. Mean duration of patient-controlled analgesia (PCA) was 15 17 hrs. During this period, an average of 12-18 demands were administered per patient, resulting in an average fentanyl consumption of 36-52 micrograms/h (0.57 0.94 micrograms/kg/h). Analgesic efficacy was good in all groups, mean pain scores ranging from 0.4 to 1.1 (actual) and 1.7 to 2.2 (retrospective). Mean duration of a single fentanyl bolus dose was highly variable, ranging from 58 to 90 min if calculated for the total observation period. Statistically significant differences were found for none of the above mentioned PCA parameters. As a trend, the adaptive-rate infusion strategy was favoured (lowest demand rate, best retrospective pain scores).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450310 TI - [Lidocaine plus fentanyl for controlling cardiovascular reactions to laryngoscopy and intubation]. AB - Administration of fentanyl or lidocaine alone often insufficiently suppresses the haemodynamic reaction to laryngoscopy and intubation. We therefore evaluated the combination of both substances in patients with good ventricular performance (EF > 60%) undergoing coronary bypass surgery. 20 patients were randomly assigned to Group 1 (G1) or Group 2 (G2). As induction agents flunitrazepam (0.025 mg/kg), fentanyl (6-7 micrograms/kg) and pancuronium (0.1 mg/kg) were used. 3 minutes prior to intubation G1-patients received saline (0.1 cc/kg) while in G2 patients lidocaine (1 mg/kg) was administered. 10 minutes after termination of the preparations for induction (M1), prior to (M2), during (M3) and 10 minutes after the end of intubation (M4) heart rate (HR), blood pressure (MAP), pulmonary artery pressure (PAP) pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured. From these values we calculated rate-pressure product (RPP), total peripheral resistance (TPR), pulmonary vascular resistance (PVR), cardiac index (CI), stroke volume (SV) and stroke index (SI). Whitney-Mann test (U-test) served for statistical evaluation. If compared to baseline (M1), induction of anaesthesia caused in both groups a significant decrease of MAP (G1: 109 to 81 mmHg; G2: 97 to 77 mmHg), CO (G1: 6.2 to 5.2 l/min; G2: 6.6 to 5.2 l/min), CI (G1: 3.3 to 2.8 l/min m2; G2: 3.5 to 2.7 l/min m2) and RPP (G1: 12701 to 10201 mmHg min-1; G2: 11309 to 8070 mmHg min-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450311 TI - [Indwelling catheters with injection ports: Is retrograde contamination of applied syringe possible?]. PMID- 1450312 TI - [Chronic pain as a psychosomatic syndrome]. PMID- 1450313 TI - [Classification of chronic pain syndromes. Multiaxial pain classification MASK]. PMID- 1450314 TI - [The concept of a multidisciplinary pain clinic]. PMID- 1450315 TI - [Oral ketamine as preferred preanesthetic medication of uncooperative patients]. AB - We report on oral ketamine for the preinduction of 3 patients who aggressively refused the commonly used induction of anaesthesia, due to young age or mental retardation. One child and two mentally retarded patients aged 30 and 31 years who were to undergo dental surgery aggressively refused the induction of anaesthesia, either by inhalation or rectal, intramuscular, or intravenous application of drugs. One of them previously injured the medical personnel and destroyed the interior equipment of a gynaecologist, who tried to perform an examination. After having received 6 to 8 mg/kg body weight ketamine in 10 ml water, which they accepted well, probably because of the long lasting fluid restriction (about 12 hours), they tolerated the induction of anaesthesia by inhalation (2 patients) or intravenously (1 child). Two patients remained awake, but calm, one fell deeply asleep. After several hours of surgery in inhalation anaesthesia they could be extubated within several minutes and discharged the same day. We conclude that 5 to 10 mg/kg oral ketamine in water which has a bioavailability of approximately 20% is a useful agent for the preinduction of patients who aggressively refuse medical treatment. Because deep sleep states cannot be excluded, we recommend a careful supervision after the application of ketamine. Nevertheless, we could discharge our patients on the same day even after long lasting surgical procedures; this makes this method useful in day case surgery. PMID- 1450316 TI - [Historical vignette (5). Brain anemia for more rapid induction of anesthesia]. PMID- 1450317 TI - Effect of thrombin inhibitors on platelet functions: comparative analysis of DuP 714 and hirudin. AB - Since thrombin plays an important role in platelet-mediated arterial thrombosis, we have examined the antiplatelet activity of a synthetic thrombin inhibitor, DuP 714 (Ac-(D)Phe-Pro-boroArg), in comparison with that of the naturally occurring inhibitor hirudin. Hirudin was slightly more potent than DuP 714 in inhibiting thrombin-induced aggregation in washed human platelets (IC50s of 72 nM and 150 nM, respectively) and in inhibiting the secretion of plasminogen activator inhibitor-I from human platelets (IC50s of 300 nM and 900 nM, respectively). In contrast, DuP 714 was more potent than hirudin in inhibiting thrombin-induced [125I]fibrinogen binding to gel purified platelets, and in inhibiting thrombin induced intracellular calcium mobilization in washed platelets. These results indicate that the tripeptide DuP 714 has comparable antiplatelet activity to the 65 amino acid hirudin. We conclude that DuP 714 may have clinical utility in the prevention of platelet-dependent, arterial thrombotic processes. PMID- 1450318 TI - Autoantibody to plasma fibrinopeptide A in a patient with a severe acquired haemorrhagic syndrome. AB - We describe a 50-year-old man with a severe acquired haemorrhagic syndrome. He had slightly prolonged clotting times using bovine thrombin, human thrombin and reptilase. His plasma contained a polyclonal IgG which interfered with the generation of fibrin monomers without inhibiting the aggregation of preformed monomers. The inhibitor delayed thrombin-induced fibrinopeptide A release. The IgG bound to insolubilized synthetic fibrinopeptide A (one binding site per molecule) and, with higher affinity, to fibrinogen (two binding sites per molecule). It did not bind to insolubilized fibrin monomers. The IgG did not impair the catalytic activity of thrombin toward a small synthetic substrate but inhibited the binding of thrombin to fibrinogen without binding to thrombin. The binding of the anti-fibrinopeptide A autoantibody to fibrinogen might have impaired thrombin-induced fibrinogen to fibrin conversion in vivo. This may have favoured the reported haemorrhagic syndrome which was associated with severe chronic renal insufficiency. PMID- 1450319 TI - Platelet prevention of oxidant lung oedema is not mediated through scavenging of hydrogen peroxide. AB - Previous studies have shown that washed human platelets attenuate oxidant oedema in isolated perfused rabbit lungs through mechanisms dependent on platelet glutathione. We hypothesized that the platelet glutathione redox cycle scavenges hydrogen peroxide in this model and thereby protects vascular endothelial cells from oxidant injury. This hypothesis was tested by asking two questions: (1) do glutathione-supplemented platelets demonstrate augmented lung protection compared with control platelets, and (2) does conjugation of platelet glutathione with 1 chloro-2,4-dinitrobenzene or inactivation of catalase with 3-amino-1,2,4-triazole decrease in vitro platelet metabolism of hydrogen peroxide? We incubated washed human platelets with reduced glutathione or glutathione monoester and observed platelet glutathione contents of 181% and 189%, respectively, compared with control values. Incubation of platelets with N-acetylcysteine did not alter platelet glutathione content. Infusion of glutathione-supplemented platelets into isolated lungs injured by purine and xanthine oxidase did not augment platelet protection compared with untreated platelets. We also found that conjugation of platelet glutathione and/or inactivation of platelet catalase did not decrease the rate constant for platelet metabolism of hydrogen peroxide. We conclude that platelets attenuate oxidant lung oedema through glutathione-dependent mechanisms other than direct scavenging of hydrogen peroxide. PMID- 1450320 TI - Lupus anticoagulants/anticardiolipin antibodies in patients with normal tension glaucoma. AB - Ocular vascular occlusive disease resulting in severe retinopathy and/or post thrombotic glaucoma has been extensively discussed in patients with lupus anticoagulant and/or anticardiolipin antibodies (LA/aCL). Inadequate circulation plays an important role in the pathogenesis of another ophthalmic entity--the normal tension glaucoma. We studied 22 patients with normal tension glaucoma (group I) and 23 with chronic open-angle glaucoma (group II) and compared them with a control group (n = 25, group III). LA, aCL, the aCL cofactor beta 2 Glycoprotein I, and other haemostatic parameters including factor VIII:C, von Willebrand factor, factors II, V, VII and plasminogen activator inhibitor were measured. Five out of 22 (22.7%) in group I, five out of 23 (21.7%) in group II and three out of 25 (12.0%) in group III had positive LA and/or aCL. These prevalences were not statistically significantly different. beta 2-Glycoprotein I was normal in all groups. No other parameters were significantly different between groups. These findings do not support the contribution of ocular microvascular occlusive disease, due to elevated aCL, in the pathogenesis of glaucomatous damage. PMID- 1450321 TI - Hereditary deficiency of antithrombin III, protein C and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening. AB - Data in the literature on the prevalence of hereditary deficiency of the natural coagulation inhibitors are conflicting. We conducted a prospective study on 680 consecutive patients with a history of venous thrombosis to determine the prevalence of hereditary deficiency of antithrombin III (AT III), protein C(PC) and protein S(PS) and to establish selection criteria for rational patient screening. The mean age of the patients at investigation was 44.3 +/- 15.4 years, while that at the first thrombotic event was 38.5 +/- 14.8 years. The total prevalence of inhibitor deficiency states was 48/680 (7.1%). 19/680 patients (2.8%) had AT III-deficiency, 17 (2.5%) PC-deficiency, nine (1.3%) PS-deficiency and three (0.4%) a combined deficiency. In 37/48 deficient patients family studies were performed and the hereditary nature was established in 19 cases (2.8% of total patient population, six with AT III-deficiency, eight with PC deficiency, four with PS-deficiency and one with a combined deficiency). Family studies in these 19 patients revealed 46 additional individual patients with a hereditary deficiency state. A positive family history was found in 15/19 (79%) with a proven hereditary deficiency state, in 153/619 (25%) of non-deficient patients and in 11/29 (38%) of deficient patients without established hereditary nature. The mean age at the first thrombotic event was significantly lower in patients with a hereditary deficiency state (26.8 years) compared with the other two groups (39.0 and 39.7 years, respectively). In all patients with a hereditary deficiency the first thrombotic event occurred before the age of 45 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450322 TI - Factor XII clotting activity and antigen levels in patients with thromboembolic disease. AB - Individuals with severe factor XII (FXII) deficiency may be prone to thromboembolic disease and this thrombophilic state may be due to insufficient contact activation dependent fibrinolysis. According to our previous study (Thromb Haemostas 1991; 65: 117-121), however, heterozygous FXII deficiency is not a strong prethrombotic risk factor, only one out of 45 obligatory or possible heterozygotes having sustained a thrombotic event. In the present study, FXII clotting activity (FXII:C) and antigen concentration (FXII:AG) were measured in 200 patients having suffered from idiopathic thromboembolism and compared with the values in 200 healthy controls. Mean FXII levels were not significantly different in thrombophilic patients and controls, and subnormal FXII values were not more frequently encountered in patients than in controls. Specific FXII activity, i.e. the ratio of FXII:C to FXII:AG, showed considerable variation in each of the two groups, but patients and controls had a similar distribution of specific FXII activity. Variations in specific FXII activity were not explained by differences in beta 2-glycoprotein I levels. In conclusion, heterozygous FXII deficiency is not a strong prethrombotic risk factor and subnormal FXII values are not more common in thrombophilic patients than in healthy individuals. PMID- 1450323 TI - Neutralization of factor X activity by factor X-specific monoclonal antibodies. AB - Factor X, a vitamin K-dependent protein, is the plasma zymogen for the active serine protease factor Xa. Factor Xa is the proteolytic enzyme for prothrombinase, the multi-protein membrane complex that catalyses the cleavage of prothrombin to thrombin. A panel of 10 monoclonal antibodies (identified by their corresponding clone numbers: 1, 2, 3, 5, 7, 26, 27, 54, 73, and 79) to factor X were produced by immunizing mice with purified factor X. All of the antibodies bound both human factor X and factor Xa in a solid-phase ELISA and binding of the antibodies was not affected by removal of Ca2+ with EDTA. In immunoblot analysis, antibody alpha HFX-54 bound to the light chain and antibodies alpha HFX-1, -5, 7, and -26 bound to the heavy chain of reduced factor X. Antibodies alpha BFX-2b, alpha HFX-27, -54, and -73 prolonged both the factor X-dependent clotting time and activated partial thromboplastin time (APTT) of normal plasma while antibody alpha HFX-1 only prolonged the APTT. None of the antibodies significantly inhibited factor X activation by purified Russell's viper venom factor X activator. In prothrombin activation assays using purified factor Xa, factor Va, prothrombin, Ca2+ and phospholipid vesicles, seven of the antibodies (alpha HFX 1, -3, -26, -27, -54, -73 and alpha BFX2b) showed some inhibition of thrombin generation ranging from 18 to 60% of the control. The decrease in factor X plasma clotting activity was most likely due to inhibition of factor Xa activity in prothrombinase, although some antibody-dependent inhibition of factor X activation may contribute to the observed inhibition of plasma clotting. Prothrombinase activity on platelets was inhibited in an identical manner by the monoclonal antibodies. When prothrombin was activated in the absence of factor Va, only antibody alpha BFX-2b inhibited activation. Calcium-independent determinants on both the heavy chain (determinants 1 and 26) and light chain (determinant 54) of factor X may play a role in prothrombin activation by prothrombinase. Other epitopes (antibodies alpha HFX-3, -27, -73) appeared to be influenced by association of factor Xa with factor Va. Topographic regions on factor X important for factor X activation and factor Xa function may be identified by the use of these monoclonal antibodies. PMID- 1450324 TI - Enhanced ex vivo proteolysis of plasma von Willebrand factor in disseminated intravascular coagulation. AB - Plasma levels of von Willebrand factor (vWf) are frequently elevated in patients with disseminated intravascular coagulation (DIC). To investigate the qualitative abnormalities of vWf and the possibility of its ex vivo modification in DIC, we analysed the multimeric composition of vWf in citrated plasma from 15 patients with DIC in the presence or absence of serine protease inhibitors (aprotinin and soybean trypsin inhibitor) and/or cysteine protease inhibitors (leupeptin, N ethylmaleimide and EDTA). The proportion of large vWf multimers in plasma prepared in the presence of cysteine protease inhibitors was higher than those without such inhibitors. The addition of serine protease inhibitors during the preparation of plasma had no effect on the relative amounts of large multimers. The relative proportion of large multimers in plasma prepared without inhibitors and the difference between plasmas prepared with and without cysteine protease inhibitors correlated with plasma plasmin-alpha 2-plasmin inhibitor complex values, but not with other plasma or serum markers of DIC (platelet count, fibrinogen, FDP, D-dimer or thrombin-antithrombin III complex). We conclude that ex vivo proteolysis of plasma vWf occurs frequently in patients with DIC and cysteine protease inhibitors can protect this degradation. PMID- 1450325 TI - The effects of type of factor VIII concentrate used in haemophilia on T-helper cell number and inhibitor incidence. AB - This review surveys the available published data on the impact of the type of factor VIII concentrate infused on T-helper lymphocyte count and factor VIII inhibitor induction in haemophiliacs. While concern has been expressed that certain products may have adverse effects on these parameters, only one trial published to date shows a significant benefit of a high purity product in reducing the rate of CD4 lymphocyte decline in HIV seropositive haemophiliacs. A number of other studies show no such significant benefit although the design of many of these might be criticized and few of them consider the potential impact of viral infection other than HIV, such as hepatitis C. More recent data on the incidence and prevalence of inhibitors in the haemophiliac population suggest that the reported high frequency of inhibitor formation for some products may lie within the expected normal range. This raises interest in why some products appear not to induce inhibitor formation, even in the group of patients at greater risk: multitransfused, severely deficient patients. The occasional reports of late onset high titre inhibitors in multitransfused haemophilia patients associated with the introduction of newer products are a matter of concern. PMID- 1450326 TI - Platelet Symposium: Recent developments in British Blood Transfusion Service and clinical practice. Proceedings. London, 8 April 1992. PMID- 1450327 TI - An overview of current trends in platelet preparation, storage and transfusion. AB - We present an overview of issues relating to preparation, storage and transfusion of platelet concentrates. The concepts of quality are described and potential benefits from leucodepletion, UVB irradiation and the use of additive solutions discussed. Emphasis is placed on laboratory evaluation of the storage lesion and in particular morphological changes of platelets during storage. PMID- 1450328 TI - Preparation of platelet concentrates after overnight hold at 20 degrees C. AB - The clinical demand for platelet concentrates has increased dramatically in the last decade, and poses logistical problems for regional transfusion centres. Pietersz et al. (Vox Sang 1989; 56: 145-150) have shown that it is possible to prepare clinically effective platelet concentrates with substantially reduced white cell contamination, whilst maintaining satisfactory levels of factor VIII:C after holding whole blood at 20 degrees C overnight. This approach offers a method of production that will allow platelet concentrates to be prepared from potentially all donations collected, without resorting to extensive out-of-hours working. Following laboratory evaluation of the procedure we were able to reproduce Pietersz's findings, although hypotonic shock response results were less favourable than observed in our routine platelet concentrates. PMID- 1450329 TI - Automated processing of leucocyte-poor platelet concentrates. AB - In view of transfusion reactions and alloimmunization associated with leucocyte contamination of platelet concentrates (PC), there is a general move towards the production of leuco-poor PC. This goal is currently pursued by the production of various PC using buffy coat and apheresis techniques. Although there is no overall consensus on the meaning of 'leuco-poor', by assuming that this refers to a level of 5-50 x 10(7) leucocytes per PC, we were able to make comparisons with available systems used in Europe. In addition to platelet and white cell counts, other markers of PC quality were assessed in some cases. These included traditional markers (such as hypotonic stress response, pH, and lactate and beta thromboglobulin levels) and newer markers (such as glycocalicin and plasma von Willebrand factor levels). Our preliminary results showed appreciable differences in platelet and white cell content of PC prepared by various types of apheresis equipment. Appreciable differences in the quality of stored PC were also observed between routine PC (non-leuco-poor and buffy coat and apheresed PC (leuco-poor). PMID- 1450330 TI - The use of mean platelet volume for evaluation of quality of platelet concentrates. AB - Mean platelet volume (MPV) was determined on whole blood and platelet concentrates (PC) prepared from units of the same blood, as well as on samples of venous blood taken from donors before plateletpheresis and on PC collected by Spectra (COBE Laboratories Ltd) and CS-3000 (Baxter Healthcare Ltd) cell separators. The mean (+/- SD) MPV for PC prepared from blood (7.18 +/- 0.76 fl, n = 12) was significantly lower than that for whole blood (8.32 +/- 0.72 fl, P < 0.02) suggesting significant separation of young, large and dense platelets together with the red cells. In contrast, the mean MPV for PC collected with Spectra and CS-3000 cell separators was 8.48 +/- 0.52 fl (n = 20) and 8.94 +/- 0.60 fl (n = 12), respectively, and was significantly higher (P < 0.01) than that determined in venous blood samples of donors taken before plateletpheresis (7.76 +/- 0.74 fl and 8.12 +/- 0.62 fl respectively). This indicates preferential separation of large platelets, which are by inference, of better quality, into PC. PMID- 1450331 TI - Glycoproteins Ib and IIb/IIIa in the quality assessment of platelet concentrates during storage. AB - We have previously shown that levels of soluble glycocalicin (GC) in plasma supernatants derived from units of platelet concentrates (PC) increase progressively during storage. We now report further studies which show that the levels of both microparticle-bound and soluble GC in PC during storage are influenced by exposure of PC samples to EDTA and treatment of PC packs with ultraviolet B (UVB) irradiation. EDTA leads to a significant increase in the release of microvesicle-bound and soluble GC, while UVB irradiation leads to a dose- and rate-dependent increase in GC release. Paradoxically, UVB leads to an unexpected decrease in supernatant levels of von Willebrand factor (vWf) during storage which contrasts with its increase in untreated, stored PC. Moreover, an increase in GC release during storage is associated with a corresponding decrease in platelet size as determined by measurement of mean platelet volume (MPV) in citrated PC. The GC release is significantly correlated with standard platelet functional tests and other new generation tests such as dMPV and supernatant levels of vWf. In addition, preliminary results show the presence of microparticle-bound and soluble glycoprotein (Gp) IIb/IIIa in the supernatant plasma of stored PC. Our results suggest that supernatant levels of GpIb, GpIIb/IIIa, and vWf, together with alteration in MPV, provide essential new informative parameters for quality assessment of PC. PMID- 1450332 TI - Platelets as immunogens. AB - An immune response to human platelet antigens (HPA), as in neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura (PTP), is the exception rather than the rule and evidence is accumulating for the importance of human leucocyte antigen (HLA) class II restriction in this situation. Platelets have only HLA class I antigens and do not cause primary HLA alloimmunization; in platelet transfusions this is due to the contaminating leucocytes. Autoimmune thrombocytopenia is more common than the alloimmune conditions. The main target antigens for platelet autoantibodies are glycoproteins (Gp) IIb/IIIa and Ib/IX. The mechanism of drug-induced immune thrombocytopenia has been re-examined in relation to the target cell orientation of the antibody and of the drug. PMID- 1450333 TI - An audit of the use of platelet concentrates in the prophylaxis of thrombocytopenic haemorrhage in a large haematology unit. AB - Platelet transfusions are valuable in the prevention of thrombocytopenic bleeding in patients undergoing chemotherapy for haematological malignancies. The commonly used threshold platelet count for transfusion of 20 x 10(9)/l was established in the 1960s when the clinical situation was very different from today. Review of the use of platelet concentrates in a large haematology unit showed lack of adherence to this threshold with the use of platelet transfusions at higher platelet counts. Major bleeding episodes occurred at counts above the threshold when additional clinical factors were operating. A lower threshold was therefore recommended and instituted. This resulted in a 20% reduction in the use of platelet concentrates with no increase in major bleeding episodes. PMID- 1450334 TI - The alloimmunized patient: effective transfusion support and newer experimental approaches. AB - Refractoriness occurs in a proportion of patients who receive multiple platelet transfusions. Alloantibodies, in particular those directed against the class I human leucocyte antigens (HLA) present on the platelet surface, are frequently associated with accelerated platelet destruction and transfusion failure. Compatible platelets for transfusion may be found by selecting donations from HLA typed individuals, crossmatching patients' sera against donor lymphocytes and platelets or both. Maintaining a large panel of HLA-typed apheresis donors is expensive and some mismatching is inevitable due to the polymorphic nature of the HLA system. Cross-matching may improve the outcome when HLA-matched donations are transfused and may also be a cost-effective strategy for the selection of compatible untyped platelets. Administration of intravenous immunoglobulin, plasma exchange and ex vivo removal of platelet HLA have been employed successfully in a few refractory alloimmunized patients but do not yet have an established role. Experimental studies in animal models suggest that it may be possible to induce tolerance to HLA and prevent alloimmunization. PMID- 1450335 TI - Thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenic purpura is an uncommon disorder, but it continues to be of considerable interest. The disease mechanisms are unclear and the aetiology is unknown. Perhaps most enigmatic of all, the mode of action of plasma therapy, which successfully induces remission in about two-thirds of cases, is wholly inexplicable. There are currently several areas of debate on the subject of thrombotic thrombocytopenic purpura. This paper addresses these points of contention: the definition of the disease, its distinction from haemolytic uraemic syndrome, the nature of the platelet aggregating factors in the plasma of patients with acute disease, the importance of the abnormalities of von Willebrand's factor observed in the acute and quiescent phases of the disease, the nature of the factor in normal plasma that induces remission, and the possible causes of the observed superiority of plasma exchange combined with plasma infusion, over plasma infusion alone. PMID- 1450336 TI - Disseminated intravascular coagulation and hepatocellular necrosis due to clove oil. AB - We describe the case of a 2-year-old child who suffered from disseminated intravascular coagulation (DIC) and hepatocellular necrosis, following ingestion of clove oil. The patient was treated with heparin and fresh frozen plasma, and, following specific haemostasis assays, with appropriate coagulation factor and inhibitor concentrates. The case demonstrates how this approach can be successfully used in the management of DIC with coexisting liver failure. PMID- 1450337 TI - Platelet imipramine binding is increased in essential thrombocythaemia. AB - A decrease in platelet serotonin content is well recognized in myeloproliferative disorders, although the basis for this is unclear. The relationship between decreased platelet serotonin and the number of serotonin transport channels in the platelet membrane was explored indirectly by measuring the number of the closely associated imipramine binding sites. Imipramine binding parameters were determined in 12 patients suffering from either essential thrombocythaemia or polycythaemia rubra vera and in 10 healthy controls. The maximal number of imipramine binding sites (Bmax) was increased in both patient groups, significantly so in those suffering from essential thrombocythaemia. This increase contrasts with a decrease in binding in other conditions known to be associated with decreased platelet serotonin. This study thus demonstrates a discrepancy in terms of reduced platelet serotonin content and increased imipramine binding on platelets from patients suffering from essential thrombocythaemia. It is suggested that further investigation of the imipramine binding site in these disorders, in parallel with measures of platelet serotonin content and uptake, is warranted. PMID- 1450338 TI - Meningococcaemia in an adult with hereditary C4b-binding protein deficiency: study of the variations of the protein S system. AB - Serial studies of the plasma protein C-protein S system were performed during the clinical course of a pregnant woman with meningococcaemia who recovered under therapy. The patient had limited purpura fulminans skin lesions and hereditary C4b-binding protein deficiency was suspected. This diagnosis was confirmed in the patient 1 year after delivery and also by family studies. During the meningococcaemia, an initial mild and transient acquired protein C deficiency was seen but no protein S deficiency was observed despite consumption of the latter protein. As C4b-binding protein partial deficiency is associated with high free protein S and protein S activity, this may have protected against acquired protein S deficiency during meningococcaemia. PMID- 1450339 TI - Intravascular platelet activation depends on the degree of stenosis of major cranial arteries in patients with atherosclerosis. PMID- 1450340 TI - Studies on the anticoagulant properties of hementin. PMID- 1450341 TI - Sociologic aspects of pregnancy. AB - Increasingly, social factors are recognized as having a major impact on pregnancy, childbearing, and prenatal care. This review examines some of the more recent societal developments that have influenced health care for pregnant women. Although human gestation is a biologic phenomena, it exists with the social context of personal needs, family, and community of the pregnant women. This social fabric determines the perception, management, and outcome of that gestation. Significant influences to examine include pregnant women in the work force; malpractice concerns of health care providers; issues related to the cost of health care in pregnancy; the legal rights of the pregnant woman versus the legal rights of the fetus; pregnancy and occupational health; and the role of stress in pregnancy outcome. PMID- 1450342 TI - Drug supplementation in pregnancy. AB - Since antiquity, there have been references in medicine to the role of nutrition in pregnancy outcome. Reviewing articles on nutrition and drug supplementation in pregnancy, one is struck by the variety of remedies that have been tried and the variety of effects that have been attributed to them. The number of herbal remedies that have been touted is astounding, and the entire science of Geophagia evolved in the hope identifying of those population-specific customs that may have had a positive effect on birth outcome as an adaptive mechanism. Most recently, there has been renewed interest in the role of nutritional and drug supplementation in pregnancy, specifically in the areas of pregnancy-induced hypertension and teratogenesis. In this article, I briefly review the role of drug supplementation in pregnancy, ranging from established needs such as iron to prevent iron-deficiency anemia to the controversies of low-dose aspirin supplementation for the prevention of preeclampsia and preconceptional folic acid supplementation for the prevention of neural tube defects. PMID- 1450343 TI - Breech presentation and shoulder dystocia in childbirth. AB - This review covers the recent literature relevant to breech presentation and shoulder dystocia. Further evidence in favor of external cephalic version at term has emerged, and the possibility of its use in women with previous cesarean section has been suggested. Attention has been given to trial of labor in selected cases of term breech presentation. The evidence to guide the method of delivery for preterm breech presentations remains inadequate. No perinatal differences have been demonstrated among the outcome of breech second-born twins delivered by external cephalic version, breech extraction, or cesarean section. The evidence in favor of elective cesarean for suspected macrosomia to prevent shoulder dystocia is unconvincing for nondiabetics and is doubtful for pregnant diabetics. The McRoberts maneuver for shoulder dystocia has not received the prominence that it deserves. PMID- 1450344 TI - Anesthesia and analgesia for labor. AB - Epidural analgesia remains the mainstay for providing pain relief during labor. The search continues to find the ideal combination of analgesic agents and administration techniques that will provide excellent pain relief for the mother yet minimize side effects to the mother and fetus. This article reviews recent studies of epidural analgesia, including the increased use of epidural opioids, patient-controlled epidural analgesia, and the complications of epidural analgesia (including effects on gastric emptying, maternal temperature control, and hemodynamic changes to the mother and fetus). Intrathecal (spinal) analgesia, especially using opioids, is also discussed. PMID- 1450345 TI - Puerperium and breast-feeding. AB - The issues related to breast-feeding and problems of the puerperium are often obfuscated by the general but outdated practice of recommending cessation of lactation. This article examines recent literature (June 1991 to May 1992) on breast-feeding and the treatment of puerperal problems, emphasizing that breast feeding may be maintained during virtually all treatment modalities. Additionally, the use of drugs to support or suppress lactation has been of interest, and the increased attention to the fertility impact of breast-feeding, breast-feeding and maternal health, and human immunodeficiency virus and breast feeding has resulted in several new articles of note. In general, the recent study of breast-feeding has identified many positive side effects, while other articles confirm that the treatment for retained placenta, postpartum pain, and puerperal infection, as discussed in recent literature, do not contraindicate breast-feeding. PMID- 1450346 TI - Delivery room management and outcome issues in the neonate. AB - Issues relevant to term newborns include screening for functional neurologic deficits that may be improved by early detection and intervention. Papers are presented that consider ocular, acoustic, and cognitive evaluations in the term neonate. Delivery room management of the meconium-stained infant remains controversial and is discussed by several authors. Data are presented regarding intubation and its role in the prevention of meconium aspiration syndrome, causes of meconium passage in utero, and its significance for neonatal outcome. In addition, illicit drug use, especially cocaine, is a significant problem among pregnant women with multiple sequelae for the fetus and newborn. Papers reviewed include a comparison of neonatal drug screening techniques, fetal effects of subacute maternal cocaine use, and follow-up data in a large cocaine-exposed cohort. The impact of the cocaine problem is growing nationally, overwhelming existing programs for medical care and rehabilitation, and mandating change at all levels of intervention. Finally, the search for a definitive indicator or predictor of birth asphyxia continues to generate literature in both the pediatric and obstetric journals. PMID- 1450347 TI - Trends in obstetric and gynecologic residency education. AB - Residencies in obstetrics and gynecology are popular with graduating medical students, especially women, and positions are filled in excess of 100%. New Accreditation Council for Graduate Medical Education special requirements have focused on several clinical areas and require demonstration of scholarly activity by faculty and 24-hour in-house faculty coverage. Other issues of current concern are resident work hours, pregnancy among residents, and training of residents in induced abortion. PMID- 1450348 TI - Sexual abuse of children and adolescents. AB - Clinicians are seeing greater numbers of children and adolescents suspected of being sexually abused. In the past, the interpretation of the medical findings was hampered by a lack of knowledge of normal anatomy and genital flora in the nonabused prepubertal child. The quality of more recent studies has been improved by the use of more appropriate controls and by the thorough evaluation of reportedly normal girls to ensure that they are truly nonabused. Such studies have provided the clinician with more accurate medical data with which to support the diagnosis of child sexual abuse. PMID- 1450349 TI - Adolescents and human immunodeficiency virus infection. AB - As of March 31, 1992, individuals 13 to 19 years of age had been diagnosed with acquired immunodeficiency syndrome; over one third were diagnosed in the past 2 years alone. Because of the long incubation period from initial infection to acquired immunodeficiency syndrome diagnosis, the majority of young adults with acquired immunodeficiency syndrome were probably initially infected as adolescents. In 1991, 34% of adolescents with acquired immunodeficiency syndrome were female, and their predominant mode of transmission was heterosexual contact. Human immunodeficiency virus seroprevalence studies of adolescents show a male-to female ratio approaching 1:1, with many human immunodeficiency virus-infected adolescent women identifying none of the standard risk. Factors such as sexual and drug experimentation, risk taking, and sense of invulnerability so characteristic of adolescence put adolescents at special risk for human immunodeficiency virus. There is no published information on if or how clinical manifestations of human immunodeficiency virus disease in adolescents might differ from those seen in adults. Medical care should be broad-based and should include access to clinical trials for new drug treatments. General knowledge levels about acquired immunodeficiency syndrome are high among US adolescents, but behavioral changes have lagged behind. All adolescents should be targeted for intensive education about human immunodeficiency virus along with interventions designed to enhance their general coping, communication, and decision-making skills. PMID- 1450350 TI - Update on pregnancy, condom use, and prevalence of selected sexually transmitted diseases in adolescents. AB - Adolescent pregnancy and its consequences continue as major sources of morbidity in the United States. A teenager who becomes a parent is at a significant disadvantage in becoming a contributing adult, both psychosocially and economically. The physician who cares for adolescents has the responsibility of helping parenting teens to find needed support so that they will be able to overcome this significant hurdle. Attention from public agencies has focused on increasing condom use as one approach to adolescent pregnancy prevention. The major advantage of using condoms is that they also prevent transmission of sexually transmitted diseases. Of note is that level of knowledge about condoms is not related to their use, and engaging in high-risk behaviors is related to a decreased likelihood of condom use. With rates of condom use estimated at less than 50%, rates of sexually transmitted disease remain high, as reported in recent surveys. PMID- 1450351 TI - Pediatric and adolescent gynecologic endocrinology. AB - Best described as a transformation from the infantile state to an accentuated dimorphic adult state, puberty is a sequence of events characterized by the secretion of gonadal hormones leading to the development of secondary sexual characteristics, gametogenesis, and reproductive function. In girls, the first signs of puberty may be evident at age 8, with the process largely completed by age 16; in boys, puberty commonly begins between ages 10 and 12 and is largely completed by age 18. Adrenarche, the secretion of adrenal androgens, starts between ages 6 and 8 and is clinically accompanied by pubarche. Premature pubarche should be diagnosed as either typical or atypical. In atypical premature pubarche, corticotropin testing is recommended to determine nonclassical adrenal enzyme deficiency of steroidogenesis. Children with either type of premature pubarche should be under continued follow-up throughout puberty. The trigger of the onset of puberty is still unknown. The presence of gonadotropin activity and possible circadian rhythm in the prepubertal years allows for new understanding in possible triggering mechanisms of puberty. Precocious puberty, which is associated with significant psychologic implications and possible pathology, must be categorized as complete precocious puberty with activation of the hypothalamic pituitary axis or incomplete precocious puberty without activation of the central axis as effective therapies are so different. The categorization does not yield diagnoses, as there are multiple etiologies within each category. The treatment of central precocious puberty with gonadotropin-releasing hormone agonists will postpone pubertal progression to a more appropriate age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450352 TI - Structural anomalies of the reproductive tract. AB - Structural anomalies of the female reproductive tract may be divided into disorders of lateral fusion and disorders of vertical fusion of the Mullerian duct system. In the past, these disorders were diagnosed at or after menarche or later in life during evaluation of various forms of reproductive tract failure, such as infertility and pregnancy wastage. Newer techniques including pelvic ultrasound and magnetic resonance imaging have allowed diagnosis in the pediatric patient and on occasion, even in utero. Surgical correction of lateral-fusion defects (didelphic, bicornuate, septate, and unicornuate uteri) have remained essentially unchanged except for surgical reconstruction of the septate uterus. Surgical correction of vertical defects (vaginal septi and cervical agenesis or dysgenesis) has received considerable recent interest with the development of newer techniques that may be more effective than the reconstructive procedures of the past. PMID- 1450353 TI - Assessment and management of premenstrual syndrome. AB - Premenstrual syndrome has recently become the subject of more rigorous scientific scrutiny. As a result, techniques exist for accurate diagnosis, and the pathophysiology of the disorder is less mysterious. At present, the disorder is thought to be the caused by the interaction of cyclic changes in estrogen and progesterone with a variety of systems, particularly neurotransmitters. Serotonin appears to play an especially important role in this regard. Increased understanding of premenstrual syndrome has enabled the development of specific treatment modalities that, unlike previous prescriptions, have demonstrated efficacy in rigorous and reproducible studies. PMID- 1450354 TI - Chronic pelvic pain. AB - Chronic pelvic pain is a common and important gynecologic problem. The causes are diverse but can usually be categorized by the astute clinician. Gynecologic causes can often, although not always, be pinpointed for specific management protocols. Highlights of helpful areas are described in terms of history, physical examination, and laboratory and endoscopic diagnosis. Therapy may be medical, surgical, psychologic, or supportive. If specific, treatment is likely to be effective in some patients whereby a cause cannot be found, yet the patient may be helped. Some patients improve without treatment. PMID- 1450355 TI - Reversible contraception for the woman over 35 years of age. AB - Methods of reversible contraception, oral contraceptives, intrauterine devices, and Norplant (systemic progestin-only contraceptive; Wyeth-Ayerst, Radnor, PA), can be used for women over 35 years of age. Oral contraceptive formulations are safe and effective for healthy women up to the age of menopause. Oral contraceptives in women who do not smoke cigarettes do not result in a significant increased risk for cardiovascular disease. The incidence of breast cancer is not increased in women who have used oral contraceptives. A slight increase was found in younger women who had been on oral contraceptives based on a reanalysis of the contraceptive and steroid hormone study of the Centers for Disease Control. A reduction in the incidence of ovarian epithelial neoplasia by 40% was found in three European case-control studies. Two intrauterine devices are currently available on the US market: Paragard (GynoPharma, Somerville, NJ) and Progestasert (Alza Corp., Palo Alto, CA). Both of these provide highly effective contraception. A World Health Organization prospective randomized study found that there was an increase in pelvic inflammatory disease rates in the first 20 days after intrauterine device insertion. The intrauterine device itself did not increase the pelvic inflammatory disease incidence rates. The Norplant system exerts its contraceptive action through ovulation inhibition and alteration of cervical mucus. The major consumer complaint is irregular or prolonged uterine bleeding, which can be controlled by oral estrogen. PMID- 1450356 TI - Breast disease. AB - Breast cancer is the leading cause of death in women between the ages of 35 and 54. It is estimated that the specialist in obstetrics and gynecology provides health care for more than half of the female population in the United States and should become familiar with both benign and malignant breast conditions. Confronted with the misconception that the disease appears in women "at risk" only and the estimate that one in every nine women born in the United States will develop breast cancer, adequate education, screening, examination, and documentation are essential in the field of breast disease. PMID- 1450357 TI - Hormone replacement therapy. AB - Although hormone replacement therapy (HRT) has been available for almost 100 years, conflicting opinions still exist about its efficacy and safety. There is uniform agreement that vasomotor instability and vaginal atrophy are totally reversible with HRT. Effective treatment of bone loss with HRT depends on the number of years of estrogen deprivation, peak bone mass, and rapidity of bone loss. Oral, transdermal, and pellet estrogens are equality effective. Mortality from coronary heart disease decreased 20% to 40% in women on HRT, yet the mechanism has not yet been ascertained. The increased risk of endometrial cancer has been confirmed, but better diagnostic techniques for detection in the precancerous state have been developed. The relationship of breast cancer to estrogen use has not been conclusive. Meta-analysis of 13 studies results in a relative risk of 1.06, whereas a large case-control study reveals a relative risk of 0.9. However, it is clear that in the average, healthy woman, low-dose estrogen replacement for less than 10 years does not increase the risk of breast cancer. Physicians are encouraged to help patients weigh the risks and benefits of HRT. PMID- 1450358 TI - Transvaginal sonography in gynecologic office practice. AB - Recent technologic developments have made transvaginal ultrasound an important adjunct to gynecologic examination in both the office and the emergency room settings. Important advantages of using transvaginal ultrasonography to supplement bimanual examination are presented and discussed. Training and equipment issues, as well as medicolegal issues, are addressed. PMID- 1450359 TI - General obstetrics. PMID- 1450360 TI - Adolescent and pediatric gynecology. PMID- 1450361 TI - Office gynecology. PMID- 1450362 TI - A prospective study of pyrogenic reactions in hemodialysis patients using bicarbonate dialysis fluids filtered to remove bacteria and endotoxin. AB - Pyrogenic reactions (PR) are a well-recognized complication of hemodialysis and have been associated with dialyzer reuse, high-flux dialysis, and bicarbonate dialysate. However, the roles of bacteria and endotoxin in dialysate for producing PR are not well defined. To determine the effect of removing most bacteria and endotoxin from the dialysate on the incidence of PR, a cohort of chronic hemodialysis patients receiving high-flux, high-efficiency, or conventional hemodialysis at three centers with bicarbonate dialysis fluids that had been filtered with a polysulfone high-flux hemodialyzer was prospectively studied. Unfiltered bicarbonate concentrate had median bacterial and endotoxin concentrations of 479,000 CFU/mL and 39,800 pg/mL, respectively. After filtration of the bicarbonate concentrate at the central proportioner, dialysate had a median 9.2 CFU/mL of bacteria and 17.8 pg/mL of endotoxin. Dialysate filtered at individual proportioning dialysis machines had a median 0.001 CFU/mL of bacteria and 0.19 pg/mL of endotoxin. Nine PR were identified among 303 patients after 28,007 hemodialysis treatments (0.3 PR/1,000 treatments). The rate of PR was similar for the three hemodialysis treatment modalities and for first-use compared with reused dialyzers. Although the PR rate in this study was lower (P = 0.046) than the PR rate of a previous study with unfiltered dialysis fluids (0.7 PR/1,000 treatments), it represents a difference of only 10 PR in over 28,000 treatments. It was concluded that filtration of hemodialysis fluids is efficacious in removing bacterial and endotoxin contamination and can result in a lower incidence of PR in patients receiving high-flux, high-efficiency, or conventional hemodialysis. PMID- 1450363 TI - Short- and long-term efficacy of total parathyroidectomy with immediate autografting compared with subtotal parathyroidectomy in hemodialysis patients. AB - A retrospective study was performed in chronic hemodialysis patients comparing total parathyroidectomy (PTX) followed by immediate autografting (IA) (total PTX+IA) with subtotal parathyroidectomy (subtotal PTX). One hundred six patients with severe, uncontrolled hyperparathyroidism were referred to this center and underwent surgery during the period from 1980 to 1990. Long-term follow-up after PTX was available in 49 of them: 28 patients had total PTX+IA and 21 had subtotal PTX. The two surgical methods were evaluated with respect to preoperative severity of hyperparathyroidism, immediate postoperative results, and long-term parathyroid status, as evaluated by an RIA measuring intact immunoreactive parathyroid hormone (intact iPTH; normal values, 15 to 65 pg/mL). The initial degree of hyperparathyroidism was comparable in the two groups. An excellent short-term control of hyperparathyroidism was achieved in the great majority (95%) of patients with either surgical procedure. However, long-term normalization of parathyroid gland activity was achieved in only one third of patients whereas 33% had elevated intact iPTH levels (> 130 pg/mL; i.e., higher than twice the upper range of normal) and 32% had low intact iPTH levels (< 15 pg/mL), consistent with permanent hypoparathyroidism. No difference was found in the immediate failure rates: 0 of 28 cases after total PTX+IA compared with 2 of 21 cases after subtotal PTX. Similarly, long-term intact iPTH levels were comparable: 400 +/- 105 versus 212 +/- 82 pg/mL (mean +/- SE; P = not significant). Interestingly, long-term serum intact iPTH levels were higher in patients with nodular (N = 18) than with diffusely (N = 26) hyperplastic glands: 556 +/- 146 versus 126 +/- 52 pg/mL (P < 0.001) and recurrence of hyperparathyroidism was more frequent with nodular hyperplasia (11 of 18) than with diffuse hyperplasia (4 of 26) (P < 0.02). In conclusion, although excellent short-term results were obtained with both procedures, satisfactory long-term control of parathyroid gland function was achieved in only one third of the patients, the other two third remaining either hypoparathyroid or developing recurrent hyperparathyroidism. Last, the histological subtype of parathyroid glands was partially predictive of the recurrence of hyperparathyroidism. PMID- 1450364 TI - Effect of vitamin B6 supplementation on plasma oxalate and oxalate removal rate in hemodialysis patients. AB - Whether pyridoxine (B6) supplements decrease plasma oxalate concentrations in patients on maintenance dialysis is unresolved. The effect of two dose levels of B6, 0.59 mmol/day (100 mg/day) over 6 months and 4.43 mmol (750 mg) after each dialysis treatment for 4 wk, on plasma oxalate and oxalate removal rate (dialysis plus urinary excretion) was studied in patients on maintenance hemodialysis. In both studies, a control group unsupplemented with B6, who remained on their regular diet, was also studied. The vitamin B6 status of the patients was assessed by the erythrocyte glutamate pyruvate transaminase activity and index before and during supplementation. No decrease in plasma oxalate or oxalate removal rate was found in either study. The plasma oxalate and oxalate removal rates of the unsupplemented hemodialysis patients were not different from those receiving B6 either before or after supplementation. These studies demonstrate that high-dose B6 supplementation does not decrease plasma oxalate concentration in a population of hemodialysis patients. PMID- 1450365 TI - Treatment of childhood nephrotic syndrome. AB - This review examines selected aspects of the treatment of the nephrotic syndrome in children. Particular attention has been paid to two groups of nephrotic children. First, children with steroid-responsive nephrotic syndrome are discussed. Recently, a series of controlled studies have provided important information regarding the optimal duration of steroid therapy. Initial episodes of the nephrotic syndrome are best treated with "long" courses of prednisone therapy (6 wk of high-dose daily prednisone followed by 6 wk of alternate-day prednisone). In contrast, relapses do as well with "short" courses (about 2 wk of daily prednisone and 2 wk of alternate-day therapy). Some children who are steroid responsive require high doses of prednisone to remain in remission. These patients may require alkylating agent therapy. The most common cause of steroid resistant nephrotic syndrome is focal segmental glomerulosclerosis. Over the past 10 yr, these patients have been treated with an intensive protocol involving multiple infusions of high-dose methylprednisolone and, in many cases, oral alkylating agent therapy. Current experience with this treatment is presented. The protocol appears to improve the outcome in children with focal segmental glomerulosclerosis, although it is believed that it is essential that these observations be confirmed by a controlled trial. There is also interest in the use of angiotensin-converting enzyme inhibitors and cyclosporine in the treatment of childhood nephrotic syndrome. The experience with these agents is briefly reviewed, but the current data are inadequate to indicate their role(s) in this condition. PMID- 1450366 TI - Glycosyl-phosphatidylinositol-anchored membrane proteins. AB - Many proteins of eukaryotic cells are anchored to membranes by covalent linkage to glycosyl-phosphatidylinositol (GPI). These proteins lack a transmembrane domain, have no cytoplasmic tail, and are, therefore, located exclusively on the extracellular side of the plasma membrane. GPI-anchored proteins form a diverse family of molecules that includes membrane-associated enzymes, adhesion molecules, activation antigens, differentiation markers, protozoan coat components, and other miscellaneous glycoproteins. In the kidney, several GPI anchored proteins have been identified, including uromodulin (Tamm-Horsfall glycoprotein), carbonic anhydrase type IV, alkaline phosphatase, Thy-1, BP-3, aminopeptidase P, and dipeptidylpeptidase. GPI-anchored proteins can be released from membranes with specific phospholipases and can be recovered from the detergent-insoluble pellet after Triton X-114 treatment of membranes. All GPI anchored proteins are initially synthesized with a transmembrane anchor, but after translocation across the membrane of the endoplasmic reticulum, the ecto domain of the protein is cleaved and covalently linked to a preformed GPI anchor by a specific transamidase enzyme. Although it remains obscure why so many proteins are endowed with a GPI anchor, the presence of a GPI anchor does confer some functional characteristics to proteins: (1) it is a strong apical targeting signal in polarized epithelial cells; (2) GPI-anchored proteins do not cluster into clathrin-coated pits but instead are concentrated into specialized lipid domains in the membrane, including so-called smooth pinocytotic vesicles, or caveoli; (3) GPI-anchored proteins can act as activation antigens in the immune system; (4) when the GPI anchor is cleaved by PI-phospholipase C or PI phospholipase D, second messengers for signal transduction may be generated; (5) the GPI anchor can modulate antigen presentation by major histocompatibility complex molecules. Finally, at least one human disease, paroxysmal nocturnal hemoglobinuria, is a result of defective GPI anchor addition to plasma membrane proteins. PMID- 1450367 TI - Five-lipoxygenase products in glomerular immune injury. AB - Leukocyte infiltration, proliferation, and activation are central pathogenetic components of immune injury in the glomerulus. Initial cellular infiltration by polymorphonuclear leukocytes (PMN) is a consequence of the deposition of immune complexes at discreet sites in the glomerulus. This is often followed by macrophage/monocyte infiltration, as well as proliferation of resident mesangial macrophages. Activated leukocytes constitute a rich source of lipid-derived bioactive autacoids, in particular, oxygenated metabolites of arachidonic acid. Here, we assess the role of the five-lipoxygenase (5-LO) family of eicosanoids, in particular, leukotrienes D4 and B4 (LTD4 and LTB4) in mediating functional and structural deterioration during immune inflammatory reactions in the glomerulus. LTD4 and other peptidyl LT appear to play a central role in the reductions in GFR in the acute phases of injury by virtue of their potent vasoactive properties, in particular, their capacity to reduce the glomerular capillary ultrafiltration coefficient, likely through contraction of smooth muscle elements in glomerular mesangial cells. The latter cells possess specific receptors for LTD4 in both humans and rat and contract in vitro when exposed to LTD4 after receptor-mediated activation of phospholipase C. LTB4, a nonvasoconstrictor LT, is released in the early phases of immune injury, likely from leukocyte sources as well as from transcellular metabolism of its precursor, LTA4, by the enzyme LTA4-hydrolase in glomerular mesangial and endothelial cells. LTB4, a potent promoter of PMN attraction, adhesion, and activation exacerbates glomerular functional impairment and structural damage by amplifying PMN-dependent mechanisms of injury. In their totality, 5-LO products of arachidonic acid contribute to the impairment of the normal glomerular filtration and sieving functions that attend acute inflammatory injury in the renal glomerulus and to the subsequent progression of glomerular destruction. This is high-lighted by the significant degree of protection afforded by the selective inhibition of arachidonate 5-LO in vivo in acute and chronic models of experimental glomerulonephritis. PMID- 1450368 TI - Heparin decreases mesangial matrix accumulation after selective antibody-induced mesangial cell injury. AB - Anti-rat thymocyte antibody-induced injury of glomerular mesangial cells is characterized initially by lysis (1 h) and is followed by proliferation (beginning at 3 to 4 days), with resolution that can include a focal increase in mesangial matrix (by 28 days). Chronic administration (every 12 h) of heparin (anticoagulant or nonanticoagulant) resulted in a decrease in antibody-induced mesangial cell proliferation, which, in turn, was associated with a decrease in the size and number of areas of focal mesangial matrix increase. The effect could not be attributed to the effect of heparin on complement, to alterations in the small numbers of la-positive cells that characterize the lesion, or to binding of antibody to glomeruli. The beneficial effects of heparin in reducing mesangial cell proliferation, with a subsequent reduction in matrix increase, suggest that mesangial cell responses are a major element in the development of at least some forms of glomerulosclerosis. The possible mechanisms by which these effects of heparin may be achieved are discussed. PMID- 1450369 TI - The functional and structural changes of the glomerulus throughout the course of murine lupus nephritis. AB - The glomerular functional and structural changes in a murine model (MRL-lpr/lpr) of progressive lupus nephritis were studied. Animals were grouped into three age categories. (I, 14 wk; II, 20 wk; and III, 26 wk). GFR fell with age (257 +/- 43, 178 +/- 50, and 150 +/- 40 microL/min for Groups I through III, respectively). Similarly, the ultrafiltration coefficient (Kf) measured on isolated glomeruli fell with time (0.030 +/- 0.006, 0.023 +/- 0.006, and 0.013 +/- 0.002 nL/s/mm Hg, respectively). Both indomethacin and a selective thromboxane receptor antagonist L-670,596 significantly improved GFR in Group II animals to values seen in Group I animals. Neither agent had any effect to increase GFR in older group III animals. L-670,596 had no effect on Kf in Group II or III animals. Glomerular morphometric evaluation demonstrated a progressive rise in glomerular tuft volume, mesangial matrix expansion, proliferation in cells, and a reduction in open capillary loops and epithelial filtration slits with age. However, because of the increase in glomerular volume, calculated surface area remained well preserved over the three respective groups (61 +/- 18, 76 +/- 15, and 71 +/- 13 microns2 x 10(3)). Therefore, the fall in Kf is likely due to a fall in hydraulic permeability (Lp). The ultrastructural component of the glomerular capillary wall that correlated best with Lp was the epithelial filtration slit number per micrometer of glomerular basement length (r = 0.73; P < 0.0001), which suggests that the structural correlate Kf is in the filtration slit length (FSL). Despite the cell proliferation and mesangial matrix expansion in early disease (Group II), the overall FSL remains stable because of a slight increase in filtration surface area and a slight reduction in epithelial slits per micrometer of glomerular basement membrane. The fall in GFR appears to be hemodynamically mediated by thromboxane A2. In older Group III animals, the fall in GFR appears to be due to a 40% reduction in FSL rather than being hemodynamically based. Thus, the early improvement in function with pharmacological agents is deceptive because considerable disease may be present because of adaptive structural changes. Eventually, with disease progression, compensating hemodynamic and structural factors fail to maintain GFR within normal limits. PMID- 1450370 TI - Hyperinsulinemia and blood pressure sensitivity to sodium in young blacks. AB - The relationship of blood pressure sensitivity to sodium with plasma insulin concentration was examined in young adult (22 to 28 yr) blacks (N = 45). The study included normotensive and borderline hypertensive subjects. Blood pressure sensitivity to sodium was determined by the change in mean blood pressure after 14 days of sodium loading (10 g of NaCl daily plus usual diet). Plasma insulin concentration was determined during an oral glucose tolerance test (OGTT). The correlation of fasting plasma insulin concentration with blood pressure or blood pressure sensitivity to sodium was not statistically significant. There was a significant correlation (after adjustment for adiposity) of blood pressure sensitivity to sodium with both the sum of insulin (r = 0.41; P < 0.01) and the 60-min plasma insulin concentration during the OGTT. The plasma insulin concentration at 60 min during the OGTT correlated significantly with the change in mean arterial pressure over a 5-yr interval (r = 0.36; P < 0.02). There was a similar significant correlation of blood pressure sensitivity to sodium with change in mean arterial pressure over 5 yr (r = 0.48; P < 0.001). These data demonstrate an association of hyperinsulinemia and blood pressure sensitivity to sodium in the young. The data also suggest that insulin may contribute to the pathogenesis of hypertension in the black population. PMID- 1450371 TI - Uremic plasma contains factors inhibiting 1 alpha-hydroxylase activity. AB - The effect of uremic plasma ultrafiltrate on calcitriol synthesis was investigated. Renal 1 alpha-hydroxylase activity was measured in normal rats infused for 20 h with 20 mL of normal or uremic plasma ultrafiltrate. Renal 1 alpha-hydroxylase activity was determined by the generation of calcitriol measured 5, 10, 20, and 30 min after the reaction was initiated by the addition of cold 25(OH)D3. The activity was significantly lower in rats infused with uremic plasma ultrafiltrate. Kidney homogenates preincubated for 3 h with uremic plasma ultrafiltrate also had significantly lower renal 1 alpha-hydroxylase activity than did those preincubated with normal plasma ultrafiltrate. In addition, the effect of the putative uremic toxin, guanidinosuccinic acid (GSA), on renal 1 alpha-hydroxylase activity was studied. Normal rats infused for 20 h with 20 mL of saline solution containing 1.5 mg/dL of GSA had significantly lower renal 1 alpha-hydroxylase activity than did rats infused with normal saline. The enzyme activity was also lower in kidney homogenates preincubated for 3 h with 4 mg/dL of GSA. Enzyme kinetic analysis revealed that the inhibition of renal 1 alpha-hydroxylase by GSA was noncompetitive. It was concluded that uremic plasma contains substances that directly inhibit renal 1 alpha-hydroxylase activity. PMID- 1450372 TI - On the mechanism of impaired distal acidification in hyperkalemic renal tubular acidosis: evaluation with amiloride and bumetanide. AB - It has been postulated that a distinctive type of hyperkalemic distal renal tubular acidosis (DRTA), referred to as voltage-dependent DRTA, results from diminished potassium and hydrogen ion secretion in the distal nephron, which is due to a suboptimal voltage (lumen negative) as a result of impaired sodium reabsorption. To test for the presence of a voltage-dependent DRTA, we used amiloride (20 mg oral, single dose) and bumetanide (2 mg oral, single dose) to inhibit and to stimulate voltage-dependent potassium and hydrogen ion secretion, respectively. Eighteen patients with hyperkalemic DRTA and seven controls with a comparable degree of renal impairment were studied. Patients were subdivided in two groups on the basis of their ability to lower their urine pH during spontaneous acidosis. Patients in Group I lowered their urine pH to the level of controls (5.29 +/- 0.06 and 5.37 +/- 0.11, respectively) whereas patients in Group II could not lower their urine pH below 5.5 (6.38 +/- 0.11). Patients in Group I and Group II had a similar degree of metabolic acidosis and hyperkalemia whereas controls had neither acidosis or hyperkalemia. Most patients in Group II and all patients in Group I had low plasma aldosterone levels. The administration of amiloride resulted in an increase in urine pH and a decrease in potassium excretion in all three groups. The finding that amiloride, presumably by obliterating the transtubular voltage as a result of blockade of sodium transport, inhibited potassium excretion to about the same extent in both groups of patients and in controls argues against the existence of a voltage-dependent defect. Bumetanide produced a fall in urine pH below 5.5 and an increase in potassium excretion in controls and Group I patients. In Group II patients, bumetanide failed to elicit a fall in urine pH below 5.5 but resulted in an increase in potassium excretion similar to that seen in controls and Group I patients. These findings suggest that a derangement other than a voltage dependent defect is responsible for the inability, characteristic of Group II patients, to lower their urine pH. It was concluded that the impairment in urinary acidification observed in patients with this subtype of hyperkalemic DRTA is due to a defect in collecting tubule hydrogen secretion that results from H+ ATPase dysfunction rather than from a voltage-dependent defect. PMID- 1450373 TI - The effects of calcium carbonate as the sole phosphate binder in combination with low calcium dialysate and calcitriol therapy in chronic hemodialysis patients. AB - Alternative phosphate binders, such as CaCO3, have been shown to be effective in the control of phosphate (P) retention in hemodialysis patients (HDP). Additionally, both oral (POC) and iv (IVC) calcitriol are purported to be of benefit in the control of secondary hyperparathyroidism. This investigation was undertaken to determine: (1) the effectiveness of CaCO3 as the sole P binder in combination with low (2.5 mEq/L) Ca dialysate; (2) the effects of discontinuing Al(OH)3 binders on both unstimulated and stimulated Al concentrations; and (3) the comparative parathyroid hormone (PTH) response to both POC and IVC in a large group of hemodialysis patients. One hundred ninety-four HDP completed part 1 of the study where CaCO3 was substituted for Al(OH)3 as the sole P binder for 6 months. A cohort of 49 HDP was given desferoximine (40 mg/kg) initially and 10 months after using CaCO3. In part 2, 54 HDP were given POC and 97 HDP were given IVC in dosages of 0.25 to 0.5 micrograms/day and 1.5 to 6.0 micrograms/wk, respectively, for an additional 6 months. In part 1, Ca and P were not different from baseline values observed with Al(OH)3 therapy. Ionized Ca increased (P < 0.05) and PTH decreased (P < 0.001) during CaCO3 therapy without vitamin D. In part 2, PTH declined 23% with IVC and was unchanged with POC in equivalent dosages (P < 0.05) at 3 months. By 6 months, PTH declined a total of 54% with IVC and was unchanged with POC. Ca, ionized Ca, P, and serum calcitriol were greater (P < 0.05) in the IVC group at 6 months. Serum Al concentrations for the entire 194 HDP fell 65% (P < 0.0001) over 12 months. In the 49 HDP cohort, serum Al fell 43.6% (P < 0.001) and stimulated Al concentrations decreased 68.7% (P < 0.0001) after 10 months. We conclude that: (1) CaCO3 is as effective as Al(OH)3 in controlling P, (2) a small decrease in PTH is observed with CaCO3 alone, (3) serologic evidence of Al excess is virtually eliminated, (4) PTH suppression with IVC is superior to that seen with POC in equivalent doses. PMID- 1450374 TI - Organization, instability and evolution of plant disease resistance genes. PMID- 1450375 TI - Nucleotide sequence and expression of two cDNA coding for two histone H2B variants of maize. AB - The complete amino acid sequences of two variants of histone H2B of maize were deduced from the cDNAs isolated from a maize cDNA library. The two encoded proteins are 150 (H2B(1)) and 149 (H2B(2)) amino acids long and shows the classical organization of H2B histones. The hydrophobic C-terminal region is highly conserved as compared to that of the animal counterparts with only 21 changes (13 conservative) among the 90 residues. Between the N-terminal part and the C-terminal region we note the presence of a basic cluster (9 residues) characteristic of histones H2B. The N-terminal third is extended as compared to the animal consensus H2B and has the same size as the H2B histone of wheat. Up to 9 acidic residues and a five time repeated pentapeptide PA/KXE/KK are present in this region. Southern-blot hybridization showed that the H2B histones are encoded by a multigenic family like the other core histones (H3 and H4) of plants. The general expression pattern of these genes was not significantly different from that of the H3 and H4 genes neither in germinating seeds nor in different tissues of adult maize. PMID- 1450376 TI - Isolation and characterization of a cDNA-clone coding for potato type B phytochrome. AB - We have isolated and sequenced overlapping genomic and cDNA clones encoding the apoprotein of a potato phytochrome. Based on the deduced amino acid sequence, which shows 77% identity to the Arabidopsis phyB and 50% identity to the potato phyA open reading frame, we suggest that these clones encode phyB phytochrome. However, the size of the deduced open reading frame of 1133 amino acids is smaller than the size of the other two phyB open reading frames characterized so far in higher plants, which contain 1171 or 1187 amino acids. The intron/exon structure within the coding region is conserved in phyA and phyB genes of various species. Southern blot analysis indicates that potato phyB is a single-copy gene. PhyB mRNA levels do not differ among different organs or different light regimes. Transcription initiation starts from two different start points which are 63 bp apart. PMID- 1450377 TI - Chloroplast tRNA(Asp): nucleotide sequence and variation of in vivo levels during plastid maturation. AB - Two chloroplast tRNA(Asp) species from barely were purified by chromatography on benzoylated DEAE-cellulose and sequenced. They differ in the modification at position 34, where queuosine (Q) is present in one of the species. The same chromatographic procedure yielded only one tRNA(Glu) species, corroborating the assumption that the same tRNA(Glu) species participates in both protein and chlorophyll biosynthesis. The level of tRNA(Glu) remains unchanged after light treatment of etiolated seedlings, whereas the amount of tRNA(Asp) decreases to about 50% relative to the level of dark-grown plants. PMID- 1450378 TI - Molecular characterization of a pea beta-1,3-glucanase induced by Fusarium solani and chitosan challenge. AB - beta-glucanases are prominent proteins in pea endocarp tissue responding to fungal infection. We have cloned and sequenced a partial pea cDNA clone, pPIG312, corresponding to a beta-1,3-glucanase in pea pods challenged with the incompatible pathogen Fusarium solani f. sp. phaseoli. The insert from the partial pea cDNA was used to probe a genomic library derived from pea leaves of the same cultivar. One of the genomic clones, pPIG4-3, contained the complete coding sequence for a mature beta-1,3-glucanase protein. The predicted amino acid sequence of the pea beta-1,3-glucanase has 78% identity to bean beta-1,3 glucanase, 62% and 60% to two tobacco beta-1,3-glucanases, 57% to soybean beta 1,3-glucanase, 51% to barley beta-1,3-glucanase, and 48% to barley beta-1,3-1,4 glucanase. Genomic Southern analysis indicates that the pea genome contains only one beta-1,3-glucanase gene corresponding to the probe used in this study. Accumulation of beta-1,3-glucanase mRNA homologous with the pPIG312 probe was detected in pea pods within 4 to 8 h after challenge with F. solani f. sp. phaseoli, f. sp. pisi, a compatible strain, or the elicitor, chitosan. In the incompatible reaction, mRNA accumulation remained high for 48h, whereas it rapidly decreased in the compatible reaction. After fungal inoculation of whole pea seedlings, the enhanced mRNA accumulation occurred mainly in the basal region (lower stem and root). This beta-1,3-glucanase mRNA was constitutively expressed in the roots of pea seedlings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450379 TI - Expression and sequence analysis of cDNAs induced during the early stages of tuberisation in different organs of the potato plant (Solanum tuberosum L.). AB - cDNA clones of two genes (TUB8 and TUB13) which show a 25-30-fold increase in transcript in the stolon tip during the early stages of tuberisation, have been isolated by differential screening. These genes are also expressed in leaves, stems and roots and the expression pattern in these organs changes on tuberisation. Southern analysis shows homologous sequences in the non-tuberising wild type potato species Solanum brevidens and in Lycopersicon esculentum (tomato). Sequence analysis reveals a high degree of similarity between the TUB13 cDNA, and a human S-adenosylmethionine decarboxylase gene. The predicted TUB8 peptide sequence shows several repeats of alanine, glutamate and proline which suggests a structural role for the encoded protein. PMID- 1450380 TI - Novel protein kinase of Arabidopsis thaliana (APK1) that phosphorylates tyrosine, serine and threonine. AB - During the course of characterizing polymerase chain reaction products corresponding to protein kinases of a higher plant, Arabidopsis thaliana, we found a DNA fragment that potentially codes for a polypeptide with mosaic sequences of two classes of protein kinases, a tyrosine-specific and a serine/threonine-specific one. Overlapping complementary DNA (cDNA) clones coinciding with this fragment were isolated from an A. thaliana cDNA library. From their sequence analyses a protein kinase was predicted composed of 410 amino acid residues (APK1, Arabidopsis protein kinase 1), in which the kinase domain was flanked by short non-kinase domains. Upon expression of APK1 in Escherichia coli cells, several bacterial proteins became reactive with anti-phosphotyrosine antibody but not with the same antibody preincubated with phosphotyrosine, convincing us that APK1 phosphorylated tyrosine residues. APK1 purified from an over-producing E. coli strain showed serine/threonine kinase activity, and no tyrosine kinase activity, towards APK1 itself, casein, enolase, and myosin light chains. APK1 was thus concluded to be a novel type of protein kinase, which could phosphorylate tyrosine, serine, and threonine residues, though tyrosine phosphorylation seemed to occur only on limited substrates. Since the structure of the APK1 N-terminal portion was indicative of N-myristoylation, APK1 might associate with membranes and thereby contribute to signal transduction. The A. thaliana genome contained two APK1 genes close to each other (APK1a and APK1b). PMID- 1450381 TI - Structure and expression of a sugarcane gene encoding a housekeeping phosphoenolpyruvate carboxylase. AB - A gene (SCPEPCD1) encoding phosphoenolpyruvate carboxylase (PEPC) was isolated from the C-4 monocot sugarcane (Saccharum hybrid var. H32-8560). SCPEPCD1 is ca. 6800 bp long, with 10 exons. The entire gene sequence from -1561 to 262 bp downstream of the putative poly(A) addition signal is reported. A low-level, essentially constitutive pattern of expression, amino acid sequence similarities to other 'housekeeping' PEPC enzymes, and the absence of DNA sequence elements conserved in the upstream region of maize and sorghum C-4-specific PEPC genes indicate that SCPEPCD1 encodes a housekeeping PEPC. Despite this, a motif proposed to act as a phosphorylation site in light-mediated activation of photosynthetic PEPC enzymes [10] is present in the SCPEPCD1 protein; evidence is presented for the presence of this site in other housekeeping PEPC proteins. PMID- 1450382 TI - Ozone-induced changes of mRNA levels of beta-1,3-glucanase, chitinase and 'pathogenesis-related' protein 1b in tobacco plants. AB - Treatment of the ozone-sensitive tobacco cultivar Bel W3 with an ozone pulse (0.15 microliter/l, 5 h) markedly increased the mRNA level of basic beta-1,3 glucanase and to a lower degree that of basic chitinase. The increase of beta-1,3 glucanase mRNA level occurred within 1 h and showed a transient maximum. Seventeen hours after ozone treatment, the beta-1,3-glucanase mRNA level decreased to lower values. The increase of basic chitinase mRNA level was delayed and was less pronounced than that of beta-1,3-glucanase mRNA. Cultivar Bel B showed only a small increase of beta-1,3-glucanase mRNA level after the same ozone treatment, whereas its basic chitinase mRNA was more strongly induced. Prolonged ozone treatment for 2 days of tobacco Bel W3 led to a persistent level of beta-1,3-glucanase and basic chitinase mRNAs, as well as to an increase of acidic chitinase and 'pathogenesis-related' (PR) 1b mRNA levels. The results indicate that genes so far considered to code for PR proteins may also be involved in the plant response to oxidative stress. PMID- 1450383 TI - Analysis of the region in between two closely linked patatin genes: class II promoter activity in tuber, root and leaf. AB - From a potato genomic library a phage lambda clone was isolated that carried nucleotide sequences of two patatin genes, thus demonstrating a close physical linkage between these two members of the patatin gene family. Sequence and restriction analysis showed the genes to be oriented in tandem. The more upstream gene was a pseudogene truncated at the 3' end, whereas the downstream gene was a class II patatin gene. In addition to a 208 bp fragment also present in patatin class I promoters, the region in between both genes contained various direct repeats also found in other patatin genes. To study the promoter activity of this intergenic region, a 2.78 kb fragment was transcriptionally fused to the beta glucuronidase gene and reintroduced into potato cultivar Bintje. Histochemical analysis revealed expression in the outermost layer of cells of the cortex, in the tuber phellogen, in or around the root vascular system, and also in the abaxial phloem layer of the vascular bundle in leaves. PMID- 1450384 TI - Dynamical behavior of psb gene transcripts in greening wheat seedlings. I. Time course of accumulation of the pshA through psbN gene transcripts during light induced greening. AB - The time course of the accumulation of the transcripts from 13 psb genes encoding a major part of the proteins composing photosystem II during light-induced greening of dark-grown wheat seedlings was examined focusing on early stages of plastid development (0.5 h through 72 h). The 13 genes can be divided into three groups. (1) The psbA gene is transcribed as a single transcript of 1.3 kb in the dark-grown seedlings, but its level increases 5- to 7-fold in response to light due to selective increase in RNA stability as well as in transcription activity. (2) The psbE-F-L-J operon, psbM and psbN genes are transcribed as a single transcript of 1.1 kb, two transcripts of 0.5 and 0.7 kb and a single transcript of 0.3 kb, respectively, in the dark-grown seedlings. The levels of accumulation of every transcript remain unchanged or rather decrease during plastid development under illumination. (3) The psbK-I-D-C gene cluster and psbB-H operon exhibit fairly complicated northern hybridization patterns during the greening process. When a psbC or psbD gene probe was used for northern hybridization, five transcripts differing in length were detected in the etioplasts from 5-day old dark-grown seedlings. After 2 h illumination, two new transcripts of different length appeared. Light induction of new transcripts was also observed in the psbB H operon. PMID- 1450385 TI - Molecular cloning of an alanine aminotransferase from NAD-malic enzyme type C4 plant Panicum miliaceum. AB - We have determined the nucleotide sequence of a cDNA encoding AlaAT-2, which is believed to function in the C4-pathway of Panicum miliaceum. An open reading frame (1446 bp) encodes a protein of 482 amino acid residues. The deduced amino acid sequence of AlaAT-2 shows 44.2 and 44.8% homology with the amino acid sequences of AlaATs from rat and human livers, respectively. Northern blot analysis showed that the gene encoding AlaAT-2 in mesophyll and bundle sheath cells was the same and transcribed similarly in the cells. The level of translatable mRNA for AlaAT-2 increased dramatically during greening. PMID- 1450386 TI - Assaying synthetic ribozymes in plants: high-level expression of a functional hammerhead structure fails to inhibit target gene activity in transiently transformed protoplasts. AB - A hammerhead ribozyme designed against the mRNA coding for the Escherichia coli beta-glucuronidase (GUS) reporter enzyme was constructed. The synthetic ribozyme appeared able to correctly cleave in vitro the target RNA. This catalytic molecule was then assayed for in vivo activity in plant protoplasts. Plasmids coding either for the ribozyme or for the GUS target gene were cotransfected into the cells by the PEG-calcium procedure and GUS gene expression monitored following transient expression by measuring the intracellular GUS enzymatic activity. Expression of the ribozyme to high molar excess over the GUS transcript did not lead to any significant decrease of GUS activity in the transfected protoplasts. Insertion of the ribozyme sequence in the 3'-untranslated region of the GUS mRNA also had no detectable effect on GUS reporter gene expression whereas the corresponding RNA appeared able to self-cleave in vitro. These results indicate that the ability of ribozymes to perform catalytic cleavage of their substrate mRNA in vitro is essential but clearly not sufficient to ensure that efficient inhibition of the corresponding target gene will occur upon endogenous expression of this catalytic RNA in the plant cell. PMID- 1450387 TI - An alfalfa (Medicago sativa L.) cDNA encoding an acidic leghemoglobin (MsLb3). AB - We have found an alfalfa cDNA clone that encodes an acidic leghemoglobin. To date, 14 alfalfa leghemoglobin clones have been identified. Five different leghemoglobin 'components' have been biochemically defined on the basis of their pI. A higher-resolution comparison, provided by sequence data analysis, identifies six leghemoglobin 'classes'. All 14 leghemoglobins are assigned to the six 'classes', which can be distributed among the five leghemoglobin 'components'. The newly identified leghemoglobin is the only member of a sixth 'class' of leghemoglobins, and it also is the only member of one of the acidic leghemoglobin 'components' IV or V. PMID- 1450388 TI - Chloroplast import of the precursor of the gamma subunit of pea chloroplast ATP synthase. AB - A cDNA clone encoding the complete precursor of the gamma subunit of the pea chloroplast ATP synthase has been isolated from a pea leaf cDNA library in lambda gt 11 following detection with antibodies to the purified gamma subunit. The cDNA insert of 1.4 kbp is smaller than transcripts of about 1.6 kb detected by northern hybridisation of RNA from both light- and darkgrown pea leaves. The cDNA encodes a polypeptide of 376 amino acid residues, of which 52 residues constitute an N-terminal presequence and 324 residues make up the mature protein. Transcription and translation of the cDNA in vitro produced a protein of 42 kDa, which was imported by isolated pea chloroplasts and processed to the mature 36 kDa subunit. PMID- 1450389 TI - cDNA sequence and expression of a phosphoenolpyruvate carboxylase gene from soybean. AB - A full-length cDNA encoding a subunit of phosphoenolpyruvate carboxylase (PEPC) was isolated from a developing seed expression library of the C3 plant Glycine max. The corresponding mRNA is present at similar levels in leaf, stem, root and developing seed. Two potential start codons exist, and the activity of protein initiated from the first such codon could be subject to regulation by protein kinase. Sequence comparison shows a similar upstream start codon in the case of the Ppc2 gene from Mesembryanthemum crystallinum, previously assumed to lack the sequences necessary for phosphorylation. The soybean encoded protein tends to resemble other 'C3-type' PEPC proteins more closely than those implicated in C4 or crassulacean acid metabolism. PMID- 1450390 TI - Organization of the major latex protein gene family in opium poppy. AB - Opium poppy latex contains a group of laticifer-specific, low-molecular-weight polypeptides called major latex proteins (MLPs). Here we describe a new member of the MLP gene family (gMLP 22) which shares 79.6% nucleotide and 84.6% amino acid sequence identity with previously isolated clones. DNA gel blot analysis indicates that the MLPs are encoded by at least eight genes which are divided into two subfamilies. The expression pattern for each subfamily, as seen in RNA gel blots, appears to be identical and laticifer-specific. PMID- 1450391 TI - Stress distribution and bone density in the lumbar spine. AB - The stress distribution of the lumbar spine was analyzed with a mechanical model of the lumbar motion segment constructed by a three-dimensional finite element method, and the results were compared with the corresponding bone density represented by the value of CT. The results showed that the stress levels in the various parts of the lumbar spine were closely related to the CT values. The authors conclude that the dynamic balance of bone growth is maintained in large part by mechanical stress. PMID- 1450392 TI - Quantitative assessment of regional wall motion abnormalities with 2DE in cases of myocardial infarction. AB - The severity, extent and localization of regional wall motion abnormalities (RWMA) were quantitatively assessed with apical biplane two-dimensional echocardiography (2DE) using a fixed-axis system, ten-segment division area method in 56 patients with old myocardial infarction (OMI). RWMA were found to be more severe in the anterior wall MI (AWMI) group than in the inferoposterior wall MI (IWMI) group and most severe in the extensive AWMI with ventricular aneurysm (EAWMI with VA) group; the extent of RWMA was smallest in the IWMI group, significantly larger in the AWMI group, and largest in the EAWMI with VA group. The location of the RWMA segments showed group-specific tendencies. For example, both coronal and sagittal apices were much more frequently involved in both the EAWMI with VA and the AWMI groups than in the IWMI group (100%, 87% and 0%, respectively, all P < 0.001). The results demonstrated that quantitative analysis of RWMA using 2DE in cases of MI is accurate and feasible. PMID- 1450393 TI - Atrial natriuretic factor and renin synthesized in cultured aortic smooth muscle cells of rats. AB - This study was designed to determine whether or not atrial natriuretic factor (ANF) is present in the vascular walls and to observe the differences in ANF between control (WKY) and stroke-prone spontaneously hypertensive rats (SHRsp). It was found that ANF is indeed present in the vascular wall of the distal aorta. HPLC analysis of the extracts from cultured aortic smooth muscle cells (ASMC) and medium revealed that intracellular ANF was mainly in the form of ANF(1-126), at levels of 0.82 +/- 0.03 (SHRsp) and 1.04 +/- 0.10 ng/10(6) cells (WKY), while the major form in the medium was ANF(99-126), at levels of 0.40 +/- 0.06 and 0.60 +/- 0.06 ng/10(6) cells, respectively. Both forms were present in smaller amounts in SHRsp than in WKY rats. On the contrary, both renin activity and angiotensin I concentrations in SHRsp cells were significantly higher than those in the WKY controls. In addition, immunocytochemistry showed positive ANF staining in cultured ASMC of both strains. The results suggest that ANF can be synthesized and secreted by cultured ASMC from rats. PMID- 1450395 TI - The purification of a guanine nucleotide regulatory protein from rat brain membrane and the measurement of its GTPase. AB - A guanine nucleotide regulatory protein (G-protein) was purified to homogeneity from rat brain membrane though a series of chromatography runs, including DE-52 ion exchange, AcA-34 ultrogel, and octyl-Sepharose columns. The purified G protein consisted of 3 subunits with molecular weights of 41000, 36000, and 8000, respectively. The alpha-subunit of the G-protein possessed high affinity GTP binding sites (k = 22.5 nmol/L) and GTPase activity (Km = 82.5 nmol/L, Vmax = 2.8 pmol/min/microgram protein), and it could be ADP-ribosylated by [adenylate-32P] NAD in the presence of pertussis toxin. These results suggest that the purified protein was Gi-protein. PMID- 1450394 TI - Identification of Leishmania donovani isolates from different kala-azar foci in China by kDNA hybridization. AB - kDNA sequence homology of Leishmania donovani isolates from three types of kala azar foci in China were analyzed by using dot and Southern hybridization with biotin- and 32P-labelled probes. The results revealed kDNA sequence heterogeneity among Leishmania donovani isolates from the three kala-azar foci: sequence homology between isolates of hill and desert foci was higher than that between hill and plain foci isolates. The kDNA hybridization technique was also found to be specific and sensitive for direct identification of Leishmania in animal tissues. In a preliminary survey, kDNA hybridization of cutaneous tissue blots of 71 dogs from endemic regions showed a positive rate of 40.8%, and the rate of double positive cases (touch blot hybridization and bone marrow smear) reached 91.3%. The direct identification of Leishmania in tissues by kDNA hybridization seems to be a useful and convenient method for epidemiological study and clinical diagnosis, especially for species/strain characterization. PMID- 1450396 TI - Metabolism in and function of the central dopamine system after transplanting adrenal medullary tissue into the rat brain. AB - The unilateral nigrostriatal pathway of rats was destroyed by microinjecting 6 hydroxydopamine (6-OH-DA), and isogenous rat adrenal medullary tissue was then transplanted into the lesioned lateral caudate nucleus. After 2 months, rotational movement was almost abolished in 40% of the transplanted rats, and it was significantly reduced in the remaining 60%. Dopamine (DA) and its metabolites contents were significantly decreased in the lesioned side of the forebrain, while no changes of NA were found. After transplanting adrenal medullary tissue, the DA contents increased by 9% only, whereas the NA contents increased significantly. In addition, by examining synaptosomes in the brains of these rats, we found that on the lesioned side of nontransplanted rats, DA uptake and DA receptor binding were increased significantly, while no such changes were seen in the transplanted group. PMID- 1450397 TI - Flow cytometry for analyzing changes in irradiated and heated HeLa S3 cells. AB - In the present study, we have compared the distribution in various phases, DNA content, cell survival and ultrastructure of HeLa S3 cells after irradiation and/or hyperthermia. After 220 KV X-ray irradiation, the Do of the survival curve was 0.94 Gy, Dq was 1.3 Gy, and N was 4.26. After Ir-192 gamma-ray irradiation, the Do of the survival curve was 2.26 Gy, Dq was 3.9 Gy, and N was 5.7. The Do of the survival curve of HeLa S3 cells after treatment at 43.5 degrees C and 44 degrees C was 2.2 min and 1.6 min, respectively. Ultrastructural changes were also observed. The marked increase of the DNA content after 6 Gy irradiation corresponded with changes of distribution in various phases, which indicated a delay in the G2 + M phase. The survival fraction after 6 Gy irradiation was less than 1%. The changes of cell cycle distribution after Ir-192 irradiation were similar to those seen after X-ray exposure. The delay of G2 + M phase after hyperthermia was dose-dependent. An obvious delay of the G2 + M phases was also observed at 24 h after treatment with X-rays plus hyperthermia. PMID- 1450398 TI - Multiple organ injuries after abdominal high energy wounding in animals and the protective effect of antioxidants. AB - Multiple organ injuries caused by high energy abdominal wounds were studied in 8 pigs and 24 dogs, and at the same time the protective effect of antioxidants in 14 dogs with multiple organ injuries was also studied. The experimental results showed that: 1) more than two organs (six organs at most) were wounded in each of the animals studied; 2) the injuries were characterized by hemorrhaging, tissue rupture and hematoma, and the main pathologic changes were local edema and necrosis; 3) the marked increase of lipid peroxide (LPO) levels in the vital organs indicated that multiple organ injuries could also involve the molecular level; 4) the injuries were due to the direct effect of pressure waves and ischemic reperfusion and not to shock or infection; and 5) antioxidants (vitamin E and Salvia miltiorrhiza Bge.) exhibited significant protective effects against multiple organ injuries through a free radical mechanism. PMID- 1450399 TI - Nude mouse interim host model for human parathyroid grafts. I. Structure and secretory function. AB - Human parathyroid (PTG) tissues from cadaver (C-PTG), fetus (F-PTG) and PTG adenoma (A-PTG) were transplanted into the kidney subcapsule of Balb/C nude mice as interim host. The structure and secretory function of the tissues were checked 30, 60, 90, 120, and 150 days after operation. The results showed that PTG tissues from all three donors could retain their structure and secretory function for more than 100 days in the nude mice. The growth and function of PTG tissues from the three donors in nude mice were compared. PMID- 1450400 TI - Nude mouse interim host model for human parathyroid grafts. II. Alteration of MHC antigens in human PTG grafts in the nude mouse. AB - Human parathyroid (PTG) tissues from cadaver (C-PTG), 5-month fetus (F-PTG) and PTG adenoma (A-PTG) were transplanted into the kidney subcapsular areas of Balb/C nude mice as interim host. Dynamic changes in the amount of tissue major histocompatibility complex (MHC) antigen present within the transplantation period were observed. The results showed that during 100 days of interim hosting, no obvious changes in the expression of tissue MHC class I antigens were seen, but the expression of tissue MHC class II antigens was significantly reduced. The changes of MHC antigens in different donor human PTG tissues were compared. PMID- 1450401 TI - Ion-exchange chromatography (IC) in the determination of serum transition metals and its clinical application. AB - The reproducibility of ion-exchange chromatography (IC) (Dionex Bio-LC) in measuring the serum transition metals Cu and Zn was found to be fairly good (CV = +/- 2.1% and +/- 2.7% within runs, and +/- 2.5% and +/- 4.3% among runs for Cu and Zn, respectively). For clinical application, sera from 20 normal volunteers and 20 patients with cancers of the digestive tract (10 early and 10 late stage cases) were analyzed. The means of serum Cu (15.54 +/- 0.31 mumol/L) and serum Zn (14.84 +/- 0.31 mumol/L) in normal volunteers were very close to the values previously determined by atomic absorption spectrophotometry in our laboratory. In the group of late stage cancer patients, the means of serum Cu (24.18 +/- 0.63 mumol/L) and the Cu/Zn ratio (1.97 +/- 0.07) were significantly elevated (P < 0.01), while serum Zn (13.01 +/- 0.61 mumol/L) was remarkably decreased (P < 0.05). There were no significant changes of serum Cu, Zn and Cu/Zn ratio in early stage cancer patients. It is concluded that the IC method is rapid, accurate, sensitive, relatively simple and could be useful in diagnosing late stage cancers of the digestive tract. PMID- 1450402 TI - Pregnancy-associated thrombocytopenia: pathogenesis and management. PMID- 1450403 TI - Interleukin-4 (IL-4) receptor expression on human T cells is affected by different intracellular signaling pathways and by IL-4 at transcriptional and posttranscriptional level. AB - Interleukin-4 (IL-4) modulates the survival, proliferation, and differentiation of a variety of hematopoietic cells. The effects are mediated through a single class of high-affinity receptors for IL-4. To understand the biologic effects of IL-4 on human T cells, we studied the regulation of IL-4 receptor (IL-4R) gene expression. We showed that IL-4R mRNA accumulation in human T cells is enhanced fourfold after activation of different secondary signaling pathways by concanavalin A (Con A), phorbol myristate acetate (PMA), the calcium ionophore A23187, and combinations of these factors. This could be ascribed to an increase in the IL-4R transcription rate and to stabilization of IL-4R mRNA resulting in a half-life of 80 to 90 minutes (v 35 to 40 minutes in resting T cells). IL-4 did enhance the IL-4R mRNA accumulation by a factor 10, which was caused by an increase in the IL-4R transcription rate and prolonging the half-life of IL-4R transcripts to 140 to 160 minutes. Finally, it was shown that A23187 induced IL 4R mRNA expression is a protein synthesis-dependent process. In contrast, Con A-, PMA-, Con A + PMA-, and Con A + A23187-induced expression of IL-4R mRNA is protein-synthesis independent. Cyclosporine A inhibited the A23187- and Con A + A23187-induced IL-4R mRNA accumulation, whereas Con A-, PMA-, and Con A + PMA induced IL-4R mRNA expression was not affected by this drug. These data indicate that expression of IL-4 receptors on human T cells can be modulated by different intracellular signaling pathways at both transcriptional and posttranscriptional levels. PMID- 1450404 TI - Detergent-resistant cytoskeleton of the surface-activated platelet differs from the suspension-activated platelet cytoskeleton. AB - This study contrasts the protein composition of the detergent-resistant cytoskeleton of platelets fully spread on glass with the cytoskeletal composition of resting platelets and platelets aggregated in suspension with thrombin. Complete Triton X-100-insoluble cytoskeletons were isolated from spread, resting, and suspension-activated platelets in the presence of protease inhibitors, solubilized in sodium dodecyl sulfate/EDTA and analyzed on reduced, one dimensional polyacrylamide gels. The protein composition of the cytoskeletons differed both qualitatively and quantitatively. Most notable were more extensive incorporation of total protein, talin, and vinculin into the cytoskeleton of spread platelets than the cytoskeleton of suspension-activated platelets. Varying the concentration and time of exposure to thrombin during suspension activation did not mimic the cytoskeletal changes of surface activation. Scanning electron microscopy, measurement of lipid phosphorus content, and varying the duration of Triton extraction did not show incomplete solubilization or nonspecific trapping of constituents in the spread platelet cytoskeleton. Proteolysis of talin was minimal in suspension-activated platelets and in platelets spread for 50 minutes. The differences in the detergent-resistant cytoskeletons of surface- and suspension-activated platelets indicate significant divergence in the physiologies of platelet spreading on surfaces and platelet activation in suspension. PMID- 1450405 TI - Thrombin interaction with platelet glycoprotein Ib: effect of glycocalicin on thrombin specificity. AB - We describe here the alteration of thrombin specificity induced by its interaction with glycocalicin. Glycocalicin is the external part of platelet glycoprotein Ib alpha (GPIb alpha) and contains binding sites for von Willebrand factor and thrombin. Taking advantage of its solubility, we have used glycocalicin in competition assays on various thrombin activities. Glycocalicin did not inhibit chromogenic substrate hydrolysis nor diisopropylfluorophosphate iPr2 (PF) incorporation, indicating that thrombin binding to GPIb does not alter access to or the conformation of the thrombin catalytic site. Glycocalicin competitively inhibited thrombin binding to fibrin (Ki = 0.1 mumol/L) and blocked fibrinogen clotting activity of thrombin. Glycocalicin also inhibited thrombin binding to thrombomodulin in a competitive manner (Ki = 3 to 5 mumol/L), but failed to prevent thrombin interaction with protein C in the absence of thrombomodulin. Previous results have indicated that GPIb binds to thrombin within the anion binding exosite masked by the carboxy-terminal hirudin peptide 54-65. The present results confirm the implication of the anion binding exosite in GPIb recognition, and further indicate that the thrombin binding site for GPIb overlaps with the thrombin binding sites for fibrin and thrombomodulin, whereas it is distinct from the thrombin binding site for protein C. Some of the structural requirements for thrombin binding to GPIb appear to be very similar to those reported for binding to its platelet receptor. However, thrombin-GPIb interaction does not appear to compete with receptor hydrolysis but rather increases the sensitivity and the rate of platelet responses elicited by the receptor. PMID- 1450407 TI - Potentiation of lipopolysaccharide-induced tumor necrosis factor-alpha expression by 1,25-dihydroxyvitamin D3. AB - The immunomodulatory hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to suppress T-cell proliferation and interleukin-2 synthesis as well as B cell immunoglobulin synthesis, while stimulating many macrophage functions. We have previously shown increased synthesis of interleukin-1 beta in lipopolysaccharide (LPS)-stimulated U937 cells after pretreatment with 10 nmol/L 1,25-(OH)2D3. We now show that 1,25-(OH)2D3 also primes the increase in U937 cell tumor necrosis factor (TNF)-alpha-accumulated mRNA after activation with LPS; 50% effective concentration (EC50) for the LPS-induced expression of TNF-alpha mRNA was decreased by two orders of magnitude after incubation with 10 nmol/L 1,25 (OH)2D3. Pretreatment of U937 cells with 10 nmol/L 1,25-(OH)2D3 also increased subsequent LPS-induced TNF-alpha mRNA expression by twofold and cell-associated TNF protein levels by more than ninefold. This potentiation was steroid-specific for 1,25-(OH)2D3 because dexamethasone inhibited TNF-alpha mRNA. The potentiation required prior exposure to 1,25-(OH)2D3 for more than 6 hours and was clearly seen after 12 hours. The finding that the sensitivity of the U937 cell monokine response to LPS was dramatically increased by 1,25-(OH)2D3 and the delayed effect on the LPS-stimulated TNF-alpha gene transcript levels indicated that 1,25 (OH)2D3 may be altering the expression of a protein(s) in the U937 cell LPS signal transduction pathway. In fact, 1,25-(OH)2D3 induced expression of the mRNA for CD14, the high affinity, cell-surface glycoprotein receptor for LPS, which could account for the enhancement of LPS-stimulated monokine gene expression by 1,25-(OH)2D3. Thus, local monokine gene expression may be regulated by both the amount and the temporal entry of the vitamin D hormone and activator(s) into the inflammatory microenvironment. PMID- 1450406 TI - Interleukin-11 promotes accessory cell-dependent B-cell differentiation in humans. AB - Interleukin-11 (IL-11) is a recently described stromal-derived cytokine that supports the growth of an IL-6-dependent murine plasmacytoma line in the presence of antibody to IL-6 and appears to act in a manner similar to IL-6 on hematopoietic stem cells. Because IL-6 is known to promote differentiation of normal human B cells, the role of IL-11 on B-cell differentiation in vitro was characterized. IL-11 does not result in significantly increased DNA synthesis or Ig secretion by purified B cells alone or B cells cultured with Staphylococcus Cowan I, a T-cell-independent B-cell mitogen. In contrast, purified B cells cultured in the presence of pokeweed mitogen (PWM), irradiated T cells, and monocytes show increased DNA synthesis at day 3 and increased IgG and IgM secretion at day 7 of culture; addition of IL-11 further augments Ig secretion without change in DNA synthesis, an effect that can only be partially blocked by monoclonal antibody to IL-6. Similar experiments confirmed that increased IgG secretion was demonstrable when either IL-11 or IL-6 was added to B cells + CD4+/45RA- T cells + monocytes + PWM; in contrast, Ig secretion was low and equivalent when CD4+/45RA+ T cells were cultured with B cells+monocytes+PWM with or without IL-6 or IL-11. Neither IL-6 nor IL-11 could significantly increase phytohemagglutinin (PHA)-induced DNA synthesis by CD4+/45RA- or CD4+/45RA+ T cells. Although PWM or IL-11 induced IL-6 mRNA expression in both CD4+/45RA- T cells and monocytes, in neither cell did IL-11 increase IL-6 mRNA expression over that noted to PWM alone. These observations support the view that IL-11 promotes differentiation of human B lymphocytes only in the presence of accessory T cells and monocytes and that a minor component of this effect may be through stimulation of IL-6 production by CD4+/45RA- T cells and monocytes. PMID- 1450408 TI - Retroviral gene transfer induced constitutive expression of interleukin-2 or interferon-gamma in irradiated human melanoma cells. AB - Cytokines are important modulators of host antitumor responses. Two of these cytokines, interleukin-2 (IL-2) and interferon gamma (IFN-gamma), are produced after antigen-induced activation of helper lymphocytes. The cytokines are released into the immediate vicinity where they either interact with the appropriate receptors on effector cell populations or are rapidly degraded. To mimic this physiologic release of cytokines at the effector-target site, we used retroviral vectors to transduce melanoma cells with the IL-2 or IFN-gamma cDNA. Five melanoma cell lines were transduced with IL-2- or IFN-gamma-containing vectors and secreted IL-2 at 1 to 40 U/mL/10(6) cells/24 h or IFN-gamma 1 to 8 U/mL/10(6) cells/24 h, respectively. After gamma irradiation, these cells continued to secrete cytokines for about 3 to 4 weeks. Secretion of IFN-gamma induced upregulation of major histocompatibility complex class I molecules in a subset of melanoma cell lines. IL-2 production by human melanoma xenografts induced tumor rejection in BALB/c nu/nu mice, showing the in vivo effect of this cytokine. This study shows that (1) human melanoma cells can be stably transduced with cytokine-containing retroviral vectors; (2) cytokines are secreted constitutively by the transduced tumor cells and have the expected biologic effects in vitro and in vivo; and (3) after gamma irradiation, cytokines continue to be secreted for several weeks. These data suggest that irradiated cytokine secreting allogenic or autologous tumor cells can be used in vaccination protocols for cancer patients. PMID- 1450409 TI - Long-term engraftment of fresh human myeloma cells in SCID mice. AB - Using highly purified myeloma cells from patient bone marrow, we established human-murine myeloma chimeras in severe combined immunodeficiency (SCID) mice and documented secretion of monoclonal human immunoglobulins (Hulgs) in the mice for up to 299 days. Monoclonality of circulating Hulgs was found only when highly purified myeloma cells were injected intraperitoneally. In contrast, injection of unfractionated myeloma marrow led to the development of polyclonal Hulgs in the SCID mice. The criteria for myeloma engraftment included prolonged presence of monoclonal Hulgs in the sera of SCID mice and/or detection of human myeloma cells in their tissues by immunohistochemical examination. Ninety-one percent (10/11) of the fresh purified myeloma specimens engrafted in the SCID mice. Fifty-five percent (6/11) of the patient samples resulted in human B-cell grafts, and 45% (5/11) were identifiable as human myeloma chimeras. Pathologic studies showed that most human plasmacytes were located in the peritoneal cavity but metastatic infiltrates were also found in other organs in 69% of the SCID-human myeloma chimeras. This chimeric model should provide a useful tool for characterization of growth modulation and microenvironmental interactions as well as a means of testing new therapeutic approaches to multiple myeloma. PMID- 1450410 TI - T-cell acute lymphoblastic leukemia--the associated gene SCL/tal codes for a 42 Kd nuclear phosphoprotein. AB - SCL/tal is a putative oncogene originally identified through its involvement in the translocation t(1;14)(p32;q11) present in the leukemic cell line DU.528. Subsequent studies have shown an upstream deletion activating expression of SCL/tal to be one of the most common genetic lesions in T-cell acute lymphoblastic leukemia (T-ALL). The cDNA sequence of SCL/tal encodes a basic helix-loop-helix (bHLH) protein with regions of marked homology to lyl-1 and tal 2, two other bHLH proteins involved in T-ALL chromosomal translocations. The bHLH motif suggests that the SCL/tal product localizes to the nucleus, binds to specific DNA sequences, and regulates transcription of a specific array of target genes. Our studies directly identify the SCL/tal product as a 42-Kd phosphoprotein that efficiently localizes to the nucleus. Deletion mutagenesis has allowed identification of a region critical for nuclear localization, a region that corresponds to the DNA-binding basic domain within the bHLH motif. Because this domain is shared by lyl-1 and tal-2, these latter putative T-cell oncoproteins probably use a nuclear localization mechanism identical to that of SCL/tal. PMID- 1450411 TI - Expression of human recombination activating genes (RAG-1 and RAG-2) in Hodgkin's disease. AB - The differentiation status of Sternberg-Reed (SR) cells is still not well defined, primarily because of their scarcity in tumor biopsies of Hodgkin's disease (HD). In this study we have determined the genomic differentiation status of SR cells by quantitation of recombinase activating gene (RAG) expression. RAG genes are selectively transcribed in immature lymphoid cells. In B cells they are silent after genomic rearrangement has occurred, whereas in T cells they are downregulated during positive selection of double-positive thymocytes into single positive cells. RNA from tumor biopsies either with numerous (11 cases) or a with few SR cells (16 cases) was assessed by a sensitive reverse transcriptase polymerase chain reaction (RT-PCR) and the results compared with established positive and negative controls. In all except two cases levels of RAG expression were within the range of those determined in negative controls. In both positive cases and in the positive control RAG mRNA was further quantitated by competitive PCR. In cases with abundant SR cells RAG expression was still below that observed in 10(-2) dilutions of positive controls. These results suggest that SR cells are derived from lymphoid cells, more differentiated than the pre-B or common thymocyte stage, which have already undergone genomic rearrangement. They show the value of assessing RAG expression by RT-PCR in the characterization of lymphoid malignancies. PMID- 1450412 TI - Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. AB - We have performed a retrospective analysis of the clinical, morphologic, and cytogenetic findings in 26 patients diagnosed between January 1969 and September 1991 with acute erythroblastic leukemia de novo (EL or AML-M6). Clonal chromosomal abnormalities were found in 20 (77%) patients (95% confidence interval [CI], 61% to 93%). Loss of all or part of the long arm (q) of chromosomes 5 and/or 7 was observed in 17 (65%) patients (95% CI, 47% to 83%). In addition, the karyotypes were often complex, with multiple abnormalities and subclones. Among the remaining nine patients, six had a normal karyotype and one each had trisomy 8, t(3;3), or t(3;5). The overall frequency of abnormalities of chromosomes 5 and/or 7 observed in our M6 patients is similar to that observed in our patients with therapy-related acute myeloid leukemia (t-AML; 99 of 129 patients, 77%), but substantially higher than that noted in our other patients with AML de novo (French-American-British [FAB] subtypes M1-M5: 52 of 334 patients, 16%). Our M6 patients with abnormalities of chromosomes 5 and/or 7 were older and had a shorter median survival (16 v 77 weeks [P = .005]) than did the M6 patients without these abnormalities. We found no correlation between morphologic features and either cytogenetic abnormalities or clinical outcome. Of note was the finding that the percentage of myeloblasts, which may account for only a small fraction of the total marrow elements when the revised FAB criteria are applied, had no bearing on prognosis. We conclude that acute erythroblastic leukemia, when defined by morphologic criteria, consists of two distinctive subgroups: one group tends to be older, has complex cytogenetic abnormalities, especially of chromosomes 5 and/or 7, and shares biologic and clinical features with t-AML; the other group, with simple or no detectable cytogenetic abnormalities, has a more favorable prognosis when treated with intensive chemotherapy. PMID- 1450413 TI - Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein (pIXY 321) enhances high-dose Ara-C-induced programmed cell death or apoptosis in human myeloid leukemia cells. AB - High dose Ara-C (HIDAC) induces programmed cell death (PCD) or apoptosis in vitro in human myeloid leukemia cells, which correlates with the inhibition of their clonogenic survival. Hematopoietic growth factors (HGFs) granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) have been demonstrated to enhance the metabolism and cytotoxic effects of HIDAC against leukemic progenitor cells. We examined the effect of pIXY 321 (a GM-CSF/IL-3 fusion protein) on HIDAC-induced PCD and related gene expressions as well as HIDAC-mediated colony growth inhibition of human myeloid leukemia cells. Unlike the previously described effects of HGFs on normal bone marrow progenitor cells, exposure to pIXY 321 alone for up to 24 hours did not suppress PCD in HL-60 or KG 1 cells. However, exposure to pIXY 321 for 20 hours followed by a combined treatment with Ara-C plus pIXY 321 for 4 or 24 hours versus treatment with Ara-C alone significantly enhanced the oligonucleosomal DNA fragmentation characteristic of PCD. This was temporally associated with a marked induction of c-jun expression and a significant decrease in BCL-2. In addition, the treatment with pIXY 321 plus HIDAC versus HIDAC alone produced a significantly greater inhibition of HL-60 colony growth. These findings highlight an additional mechanism of HIDAC-induced leukemic cell death that is augmented by cotreatment with pIXY 321 and may contribute toward an improved antileukemic activity of HIDAC. PMID- 1450414 TI - Expression of the novel intermediate filament-associated protein restin in Hodgkin's disease and anaplastic large-cell lymphoma. AB - In this study, the expression of the novel intermediate filament protein Restin in human tissues was analyzed. Restin expression was studied by immunohistochemistry using polyclonal and monoclonal antibodies. Restin was not detected in normal tissues, a range of B- and T-cell non-Hodgkin's lymphomas, and nonlymphoid tumors. However, Restin was present in Reed-Sternberg cells and variants thereof in Hodgkin's disease, with the exception of the lymphocyte predominant, paragranuloma subtype. Restin was also highly expressed in anaplastic large-cell lymphoma (so-called Ki-1 lymphoma). As expected, Restin was also expressed in Hodgkin cell lines L428, L428KSA, Co, and KM-H2 and the anaplastic large-cell lymphoma cell line Karpas 299, which was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, as well as Northern blotting. The presence of Restin in both Hodgkin's disease and anaplastic large-cell lymphoma is intriguing and might indicate a role of this structural protein in the pathogenesis of both conditions. PMID- 1450415 TI - Human macrophage colony-stimulating factor levels are elevated in pregnancy and in immune thrombocytopenia. AB - Plasma macrophage colony-stimulating factor (M-CSF) levels were measured by enzyme immunosorbent assay (ELISA) using horse and rabbit polyvalent antibodies raised against human M-CSF purified from urine (hM-CSF). Plasma M-CSF levels in nonpregnant female controls were 364 +/- 69 U/mL (mean +/- SD, n = 20). Pregnancy results in significant elevation of circulating M-CSF levels (541 +/- 164 U/mL, n = 46, P < .0005). M-CSF levels were increased by 28 weeks' gestation and did not increase further in later pregnancy. M-CSF levels were also measured in 20 female controls before and after commencing on the oral contraceptive pill. There was no effect of the contraceptive pill on plasma M-CSF levels (364 +/- 69 U/mL before v 373 +/- 66 U/mL after commencing on the pill). In 28 nonpregnant patients with untreated immune thrombocytopenic purpura, (ITP), plasma M-CSF levels were significantly increased (797 +/- 402 U/mL, n = 28, v 364 +/- 69 U/mL in controls, N = 20, P < .0005). Pregnant ITP patients had higher levels of plasma M-CSF (929 +/- 327 U/mL, n = 25) than nonpregnant patients, but this difference was not significant. Elevated levels of M-CSF in ITP may reflect activation of the reticuloendothelial system (RES), which could result in positive feedback to increase the destruction of platelets. The increase in M-CSF associated with pregnancy could contribute to the exacerbation of latent ITP in pregnancy. PMID- 1450416 TI - Eosinophil peroxidase deficiency: morphological and immunocytochemical studies of the eosinophil-specific granules. AB - Five eosinophil peroxidase (EPO)-deficient subjects were identified from 131,000 peripheral blood samples examined for routine automated analysis. The EPO deficient eosinophils of these subjects met the main criteria established for EPO deficiency: absent or strongly decreased reaction for peroxidase, absent or strongly decreased staining with Sudan Black, and an increased ratio of the granule core volume to the total granule volume. In this report we show that this granule alteration is caused mainly by a decrease of its volume, particularly of the matrix, and that two other matrix proteins, eosinophil cationic protein and eosinophil derived neurotoxin, appear to be present in normal amounts in the EPO deficient granules. PMID- 1450417 TI - Prevalent skipping of an individual exon accounts for shortened protein 4.1 Presles. AB - An asymptomatic shortened variant of protein 4.1 (-8.5 Kd) was first recognized in the red blood cells and designated protein 4.1 Presles. We show here that the missing segment belongs to the 22/24 Kd domain. Protein 4.1 cDNA from reticulocytes was amplified, mapped, and sequenced. The truncation appeared to result from the prevalent skipping of an individual and alternatively spliced exon, also called motif II, whereas this motif is preferentially retained under normal conditions. The same phenomenon was observed in lympho-blastoid cells. Sequencing over 80 bp of intronic sequences 5' and 3' of motif II failed to reveal any change. A new alternative splice site was incidently found 81 nucleotide downstream of motif II in both normal and truncated 4.1 mRNA. PMID- 1450418 TI - Effects of leukocyte depletion and UVB irradiation on alloantigenicity of major histocompatibility complex antigens in platelet concentrates: a comparative study. AB - Recent technologic advancement enables us to prepare leukocyte-depleted or UVB irradiated platelet concentrates for possible prevention of primary HLA alloimmunization. However, it is yet not known which of these two approaches is more efficacious. Because well-controlled studies cannot be easily conducted in human subjects to answer this question, a series of experiments were performed using a mouse transfusion model. The results showed that 100% of CBA mice with H2k haplotype developed antibody to donor H2d major histocompatibility complex (MHC) antigens after two weekly transfusions of platelet concentrates containing 2000 leukocytes/microL. In contrast, only 50% of the mice became alloimmunized after receiving platelets containing < or = 2 leukocytes/microL. More impressively, none developed anti-H2d antibodies after receiving two platelet concentrates irradiated with 1,200 mJ/cm2 UVB. UVB irradiation was found to be equally effective in reducing the alloantigenicity of platelet concentrates regardless of whether they contained more than a fully immunogenic dose of leukocytes. The antibody titers determined after five weekly transfusions also supported the observation that UVB irradiation was more efficacious than a 3-log leukocyte depletion in the prevention of primary alloimmunization to MHC antigens. In addition, the studies showed that only transfusions of UVB irradiated platelet products could induce the suppression of immunologic responses to donor MHC antigens in recipients and the induced immunologic suppression could not be further enhanced by gamma irradiation or by leukocyte depletion. PMID- 1450419 TI - Bone marrow transplantation for peripheral T-cell lymphoma in children and adolescents. AB - We report nine children with relapsed (n = 8) or high-risk (n = 1) peripheral T cell lymphoma (PTCL) who underwent autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16. The median age of these patients at time of BMT was 6.5 years (range 2.5 years to 14 years). Three were transplanted with active disease after failing salvage chemotherapy. Of the other six, one was transplanted in first complete remission (CR) and five in second or subsequent CR. Of these nine patients, eight are free of disease a median of 25 months after BMT (range, 6 to 48 months), with an estimated 2-year relapse-free survival (RFS) of 89%. Six of these eight patients have been followed for 12 or more months after BMT, and in each their current remission exceeds their longest previous remission duration. The toxicity of the TT/TBI +/- VP-16 regimens was significant but manageable, predominantly consisting of severe mucositis. For a comparison, we reviewed retrospective data on the six additional children and adolescents with PTCL who underwent BMT during the 3-year period preceding this phase I/II study. The median age at BMT of these six patients was 19 years (range 15.5 years to 20 years). These patients were prepared for BMT with a variety of other regimens. One had no response to BMT and the other five relapsed at 1.5 to 5 months after BMT (median, 3 months) with an RFS of 0%. Our data suggest that thioTEPA plus TBI, with or without VP-16, is an effective preparative regimen for BMT for young patients with relapsed or high-stage PTCL and leads to prolonged RFS. PMID- 1450420 TI - Expansion of a paroxysmal nocturnal hemoglobinuria (PNH) clone after cyclosporine therapy for aplastic anemia/PNH syndrome. PMID- 1450421 TI - Circulating endogenous granulocyte colony-stimulating factor levels after bone marrow transplantation. PMID- 1450422 TI - Role of busulfan pharmacokinetics on outcome after bone marrow transplantation for acute myelogenous leukemia. PMID- 1450423 TI - Graft-versus-host disease or graft-versus-host-like syndrome. PMID- 1450424 TI - Microtubule organization in lymphoid malignancies. AB - The abnormal organization of actin-containing microfilaments and vimentin containing intermediate filaments in neoplastic lymphocytes of T and B cell origin has been described. We investigated microtubules of pathologic cells from 34 lymphoid malignancies, by immunofluorescence microscopy, using monoclonal tubulin antibody. In most cases, apart from two cases of lymphoma, one T cell lymphoma and one B cell lymphoma, interphase leukemia cells, lymphoma cells, and myeloma cells were shown to contain well-organized microtubules which were associated with a microtubule organization center at one end. In the cells of a patient with T cell lymphoma, although microtubules were not visible in the lymphoma cells from lymph nodes, they became visible after 72 hours in culture with concanavalin A (Con A) and interferon alpha. Cap formation was observed with antitubulin monoclonal antibody in the peripheral blood lymphocytes from a chronic lymphocytic leukemia patient, but well-developed microtubules were observed on other occasions in the same patient. There were no obvious structural differences between microtubules in T and B cell lymphoid malignancies, but leukemia cells and lymphoma cells with irregularly shaped nuclei, such as adult T cell leukemia cells and B cell lymphoma cells with cleaved nuclei, had complicated microtubules surrounding their irregular nuclei. In general, after blastogenic stimuli with phytohemagglutinin-P (PHA-P), Con A, and pokeweed mitogen (PWM), the development of the microtubules was proportional to the incorporation of 3H thymidine (3H-TDR). In most cases, after incubation with granulocyte colony-stimulating factor (G-CSF) and interferon alpha, the number of intact cells decreased and the number of degenerated cells increased, but the intact cells had intact microtubules. PMID- 1450425 TI - Optical evaluation of red blood cell geometry using micropipette aspiration. AB - Although red blood cell (RBC) geometry has been extensively studied by micropipette aspiration, the small size of RBC and pipettes vs. the optical resolution of light microscopy suggests the need to consider potential errors. The present study addressed such difficulties and investigated four specific problems: (1) use of exact equations to calculate RBC membrane area and volume; (2) calibration of the pipette internal diameter (PID); (3) correction for a noncylindrical pipette barrel; (4) diffraction distortion of the RBC image. The observed PID represents a cylinder lens enlargement that can be theoretically derived from the glass/buffer refractive index ratio (1.49/1.33 = 1.12). This enlargement was experimentally confirmed by: (1) studying pipettes bent to allow measurement through the barrel (horizontal) and at the orifice (vertical), with a resulting diameter ratio of 1.12 +/- 0.01; (2) and by replacing the surrounding buffer with immersion oil and hence abolishing the lens phenomenon (ratio = 1.12 +/- 0.02). In addition, use of aspirated oil droplets demonstrated a 3.2 +/- 0.2% error when the PID is focused at a sharp, maximum diameter. The average pipette cone angle was 1.49 +/- 0.09 degrees and varied considerably with pipette pulling procedures; calculated tongue geometry inside the pipette was affected by the noncylindrical pipette barrel. The RBC diffraction error, demonstrated by touching two aspirated cells held by opposing pipettes, was 0.091 +/- 0.002 microns. The PID, cone angle, and diffraction artifacts significantly (p < 0.001) affected calculated RBC geometry (average errors up to 5.4% for area and 9.6% for volume). Two new methods to calculate, rather than directly measure, the PID from images of a single RBC, during either osmotic or pressure manipulation, were evaluated; the osmotic method closely predicted the PID, whereas the pressure method markedly underestimated the PID. Our results thus confirm the need to consider the above-mentioned phenomena when determining RBC geometric parameters via micropipette aspiration. PMID- 1450426 TI - Locomotion of human bone marrow and peripheral blood leukocytes is associated with maturational stage and altered in malignancy. AB - Using high-resolution phase contrast time-lapse microcinematography, slow movements (0.8-2.0 microns/minute) of human myeloblasts, monoblasts, and megakaryocytes can be recorded. Upon maturation to promyelocytes, motility is lost until cells have reached the stage of metamyelocytes (0.4 microns/minute). Motility increases sharply following maturation into segmented neutrophils (20.4 microns/minute). Monocytes and promonocytes display a mean track velocity of 7.1 microns/minute. The distribution of lymphocyte velocities is not bell-shaped but shows three maxima of 2.1 microns/minute, 7.8 microns/minute, and 18.4 microns/minute. Atypical lymphocytes from patients with infectious mononucleosis belong to the fast group, whereas lymphocytes activated in vitro by mitogens belong to the slow group. Red blood cell precursors from normal human bone marrow do not move actively. In contrast, erythroleukemic blasts show a motility comparable to normal myeloblasts. Similarly, acute promyelocytic leukemia cells move at 6.7 microns/minute, while their normal counterparts are sessile. Increased motility is also observed in blast cells from a variety of acute myelogenous and lymphoblastic leukemias. PMID- 1450427 TI - Stress platelets in normal individuals and patients with idiopathic thrombocytopenic purpura. AB - To test the hypothesis that stress platelets (SPs) described by Tong et al. in rats may be a parameter of young platelets in humans, we examined and characterized SPs in normal individuals and in patients with idiopathic thrombocytopenic purpura (ITP). Our results indicated that SPs comprise about 1.2% of the circulating platelets in normal individuals and 2.6% in ITP patients. The configuration of SPs as well as of various irregular forms of circulating platelets was found to be supported by synergism of both the platelet microfilaments and microtubules. SPs showed some segmentation, the degree of which was similar in normal individuals and ITP patients, and they underwent further segmentation during in vitro incubation, mainly promoted by microtubules, so that they sometimes appeared like discoid platelets in a chain. These observations suggest a new mode of production of discoid platelets in the circulation. Thus, identification and enumeration of SPs may be useful for evaluating thrombocytopoiesis in humans. PMID- 1450428 TI - Stress platelet: a platelet equivalent of stress reticulocyte. PMID- 1450429 TI - Bone marrow cell differential counts obtained by multidimensional flow cytometry. AB - Five-dimensional flow cytometric analysis of normal bone marrow aspirates was utilized to determine the frequency of neutrophils, eosinophils, monocytes, lymphocytes, nucleated erythrocytes, reticulocytes, platelets, and a cell population that included blasts of each of the cell lineages, megakaryocytes, plasma cells, and basophils. Each of these bone marrow cell populations had unique features with respect to forward light scatter, orthogonal light scatter, and staining with Thiazole-Orange, LDS-751, and CD45 labeled with Phycoerythrin (PE). The identity of the cell populations was verified by sorting each of the cell populations and subsequent light microscopic examination of the cells. The frequencies of the nucleated bone marrow cell subpopulations of 50 normal donors were for neutrophils, mean 72.3%; SD +/- 5.1; 95% limits, 70.9-73.8%; eosinophils, mean 1.8%; SD +/- 1.3; 95% limits, 1.4-2.1%; monocytes, mean, 2.8%; SD +/- 1.2; 95% limits, 2.5-3.1%; lymphocytes, mean 12.1%; SD +/- 3.6; 95% limits 11.1-13.2%; nucleated erythrocytes, mean 8.9%; SD +/- 3.9; 95% limits, 7.8-10.1%; and the cell population that included blasts of each of the cell lineages, megakaryocytes, plasma cells, and basophils, mean 1.6%; SD +/- 1.2; 95% limits, 1.3-1.9%. The percentage of reticulocytes in bone marrow aspirates from 50 normal donors correlated with the reticulocyte frequency in the peripheral blood of these donors. However, the mean frequency of reticulocytes was significantly greater (p < 0.0001) in bone marrow (mean 2.19%; SD +/- 0.88) than in peripheral blood (mean 1.71%; SD +/- 0.88). The technique could discriminate between immature and mature reticulocytes based on the brighter staining with both Thiazole-Orange and LDS-751 of the immature reticulocytes. This was confirmed by cell sorting of both reticulocyte populations, which revealed larger clumps of New Methylene Blue staining material in the brighter Thiazole-Orange and LDS-751 stained reticulocytes. The immature reticulocytes were present in normal bone marrow, but not in normal peripheral blood. As expected, a significantly greater frequency of nucleated cells was found in bone marrow aspirates (mean 0.85%; SD +/- 0.59) than in peripheral blood (mean 0.20%; SD +/- 0.11). The frequency of platelets was significantly lower in bone marrow (mean 1.24%; SD +/- 0.69) than in peripheral blood (mean 2.94%, SD +/- 1.14). Flow cytometric bone marrow analysis can provide clinical laboratories with a technique that generates quantitative bone marrow cell differentials and potentially can reduce the need for light microscopic examination of bone marrow smears. PMID- 1450430 TI - Kinetics of granulocyte deformability following exposure to chemotactic stimuli. AB - In order to quantitate the kinetics of granulocyte deformability changes consequent to chemotactic stimulation, transit times (TT) of neutrophils through 8-microns diameter pores were studied via a modified cell transit analyzer (CTA). Cells isolated from normal human blood were tested at 20-second intervals for 5 minutes following stimulation with N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) or zymosan-activated plasma (ZAP). The effects of cytochalasin B (CB), N ethylmaleimide (NEM), and ibuprofen were also evaluated. Salient results included: (1) greater TT with increasing fMLP concentration (0.01-100 nM) with a peak response at 40-60 seconds followed by a return to or toward control at 5 minutes; (2) longer TT at 60 seconds for at least 75% of the cells at all fMLP concentrations, yet for 1 nM at 5 minutes nearly one half had TT less than unstimulated cells; and (3) similar temporal responses during a 5-minute period to ZAP simulation, with a nonlinear relation between cell rigidity and F-actin content. CB (20 microM) and NEM (1 mM) caused an immediate 30% to 35% decrease of TT for unstimulated cells; ibuprofen (10-1000 micrograms/ml) did not affect unstimulated TT, yet significantly reduced the response to fMLP and ZAP. Cell volume, as judged by CTA pulse height, decreased following fMLP stimulation, thus indicating that cell swelling does not contribute to the longer pore transit times of activated granulocytes. Our results, combined with literature reports describing microvascular occlusion by neutrophils, strongly suggest the importance of kinetic rather than static studies of granulocyte deformability; further, they indicate the usefulness of the modified CTA for such measurements. PMID- 1450431 TI - Epidermal growth factor (EGF) expression in human salivary glands. An immunohistochemical study. AB - Epidermal growth factor (EGF) is a biologically active peptide involved in differentiation, growth, regeneration and repair of human and animal tissues. Quantitative biochemical studies showed in man the highest concentration of EGF in the parotid gland. The aim of the present study was to define EGF immunolocalization in the individual segments of the human major salivary glands (salivon). The material consisted of sections obtained from the surgically removed salivary glands: parotid, submaxillary and sublingual. Immunohistochemical studies were performed by PAP method using monoclonal antibody against human epidermal growth factor. EGF expression was found almost exclusively in the efferent pathways of the salivary glands, mostly in the intercalated ducts and Pfluger salivary tubules. These segments of the salivon are most developed in the parotid gland in which the staining was stronger than in other salivary glands. PMID- 1450432 TI - Adenosine mediation of mesenteric blood flow. AB - The mesenteric circulation is regulated by multiple mechanisms, there is sufficient reason to support the suspicion that local metabolic factors are especially important in the control of intestinal vasculature. Of these, adenosine, a purine nucleoside and mesenteric vasodilator, may be the messenger of the intestinal tissue to signal appropriate responses of the intestinal vessels. The evidence supporting the candidacy of the nucleoside as a local regular of mesenteric circulation may be summarized, as follows: Adenoside is present in the tissue of the gut in measurable quantities. Exogenous adenosine is a powerful dilator of mesenteric resistance vessels. Blockade of adenosine receptors in the mesenteric circulation interferes significantly with three autoregulatory phenomena, i.e., postprandial hyperemia, pressure-flow autoregulation, and reactive hyperemia. The evidence which weakens the role of adenosine as mesenteric vasoregulator includes: Findings in several reports that adenosine depressed intestinal oxygen consumption. The failure of adenosine receptors to inhibit some autoregulatory hyperemias of the gut and the rather limited amount of evidence regarding tissue adenosine release in autoregulatory responses of the gut's vasculature. PMID- 1450433 TI - Ornithine decarboxylase in large bowel mucosa: regulation by gastrin, secretin and EGF. AB - Rats were fasted 48 h and then injected once with either saline, pentagastrin, EGF, secretin or combinations of secretin and pentagastrin or EGF. Another group of rats was fasted and refed. Animals were killed 4 h later and ODC assayed in mucosa of the cecum, proximal colon, and distal colon. EGF significantly increased ODC activity in all 3 tissues. Secretin had no effect by itself on ODC or ODC stimulated by EGF. Pentagastrin significantly increased ODC of the cecum, and secretin completely inhibited the effect of pentagastrin. Refeeding fasted rats significantly induced activity in all three tissues. Immunocytochemistry using a highly specific polyclonal ODC antibody showed that ODC was confined to the crypt cells of the proximal colon. Antibody dilution techniques demonstrated that gastrin, EGF and refeeding increased the level of enzyme in these cells. Refeeding in addition caused the appearance of enzyme in surface epithelial cells. These results showed that colonic mucosal ODC is present in proliferative cells and is regulated by the same peptides known to regulate growth in this tissue. Colonic mucosal ODC also responds the same way as it does in the oxyntic gland and small bowel mucosa. PMID- 1450434 TI - Aminergic control of vasopressin secretion in the conscious rat. AB - The influence of aminergic pathways on basal and stimulated vasopressin (AVP) release was studied in conscious rats, the stimulus for hormone release being an intracerebroventricular (ICV) injection of 5 microliters 0.85M sodium chloride. The animals were treated with either phenoxybenzamine, propranolol or haloperidol prior to administration of the central hypertonic stimulus. Phenoxybenzamine elevated basal plasma vasopressin concentrations, while propranolol and haloperidol had no effect. The secretion of AVP in response to the hypertonic stimulus was potentiated by phenoxybenzamine and haloperidol, but the effect of propranolol was equivocal. The antagonists had no effect on basal arterial pressure at the time of hypertonic saline administration or the pressor response to ICV sodium chloride. PMID- 1450435 TI - Effect of vasopressin and V1 receptors blockade on hypotensive action of ANP in normotensive (WKY) and spontaneously hypertensive rats. AB - The aim of the study was to find out whether vasopressin (AVP) modifies hypotensive and heart rate accelerating effects of atrial natriuretic peptide (ANP) in normotensive (WKY) and spontaneously hypertensive (SHR) conscious rats. The effect of i.v. administration of 1; 2 and 4 micrograms of ANP on blood pressure (MP) and heart rate (HR) was compared during i.v. infusion of 0.9% NaCl (NaCl), NaCl+AVP (1.2 ng kg-1 min-1) and NaCl+dEt2AVP (V1 receptors antagonist, 0.5 microgram kg-1 min-1). AVP increased MP in SHR and WKY and decreased HR in SHR. V1 antagonist decreased MP and increased HR only in SHR. In SHR ANP decreased MP and increased HR during NaCl, AVP and V1 antagonist infusion. In WKY these effects were observed only during AVP administration. In each experimental situation hypotension and tachycardia induced by ANP were greater in SHR than in WKY. In both strains ANP induced changes in MP and HR were enhanced during AVP in comparison to NaCl infusion. V1 antagonist did not modify effects of ANP in WKY and SHR. The results indicate that ANP abolishes hypertensive response induced by blood AVP elevation and that the basal levels of endogenous vasopressin acting through V1 receptors does not interfere with hypotensive action of ANP neither in WKY nor in SHR. PMID- 1450436 TI - Atrial natriuretic peptide inhibits neurohypophysial hormones' release in the rat (in vitro and in vivo studies). AB - Intracerebroventricular hANP (50 nmol) inhibits release of vasopressin and oxytocin following dehydration as well as after haemorrhage. 10 nmol/L hANP markedly inhibits vasopressin and oxytocin release in vitro from the neurointermediate lobes both under basal condition as well as during stimulation with excess (56 mM) potassium. It is suggested that ANP may serve as a modulator of vasopressin and oxytocin release. The respective processes are localized, at least in part, at the neurohypophysial level. PMID- 1450437 TI - Cell membranes as targets for anti-cancer drug action. AB - A variety of studies strongly hint that cell membranes can be important targets for new and existing anti-tumor drugs. Traditionally, the search for new anti cancer agents has focused on compounds designed to act on the biosynthesis, stability or function of DNA; it may be timely, however, to broaden our search horizon and consider targets outside of the nucleus. Thus, the cell membrane as well as membraneous organelles may well play a key role in the future of anti tumor drug development. PMID- 1450438 TI - Bone metastasis in breast cancer. AB - Bone metastases in breast cancer are common and frequently lead to serious skeletal related morbid complications. Metastases develop in areas of metabolically active trabecular bone. It is presumed that breast cancer cells undergo the same stepwise process for metastases development as demonstrated in other tumor types. The specific factor or factors responsible for the osteotropism of breast cancer have not been identified. The morbid events associated with skeletal metastases, such as pathologic fracture, and spinal cord compression, may be assessed objectively by a variety of techniques including skeletal radiography, radionuclide scanning, computed tomographic scanning and magnetic resonance imaging. Biochemical parameters or markers of skeletal metastases are not sensitive enough to detect clinically occult disease. Therapeutic interventions for bone metastases include local and systemic therapies. Surgery and radiation therapy are most frequently used for relief of pain or impending fracture, or when bone fracture or neurologic compromise has already developed. Systemic treatment of bone metastases appears to be as effective as systemic treatment of other metastatic sites. Both hormone and chemotherapy may provide significant palliation. Clinical research suggests that the adjunctive use of bisphosphonates may significantly reduce the incidence of skeletal-related morbid events associated with osteolytic bone disease. Future research efforts directed at determining the osteotrophic factors responsible for bone metastases in breast cancer, the pathophysiology of the bone remodeling process in metastatic disease and the prophylactic use of bisphosphonates may lead to significant clinical benefit for those in whom bone metastases from breast cancer develop. PMID- 1450439 TI - Therapy of patients with metastatic breast cancer with 5-fluorouracil, leucovorin and carboplatin. AB - Thirty-four women with metastatic breast cancer were treated at the National Cancer Institute of the National Institutes of Health, with a regimen of leucovorin (L), 500 mg/m2 i.v. over 30 min, followed in 1 h by 5-fluorouracil (5 FU), 375 mg/m2 i.v. bolus on days 1-5, and carboplatin (CBDCA), 50-100 mg/m2 i.v. bolus on days 2-4, every 28 days. All patients had received previous combination chemotherapy with at least one regimen (29 patients with 5-FU-containing regimens). CBDCA, 100 mg/m2 on days 2-4, resulted in grade 4 neutropenia in 10 out of 11 patients associated with sepsis in all 10 patients. CBDCA, 75 mg/m2 (seven patients) and 50 mg/m2 (15 patients), resulted in grade 4 neutropenia in six and eight patients, and neutropenic sepsis in five and two cases, respectively. Grade 4 thrombocytopenia occurred in 10, five and two patients receiving 100, 75 and 50 mg/m2 of CBDCA, respectively. Other toxicities included grade 3/4 mucositis in 18 patients and grade 3/4 diarrhea in 10 patients. Twenty nine patients were evaluable for response, with one pathologic complete response (3%), two partial responses (6%), 18 stable disease (53%) and eight (24%) progressive disease. Sites of response included bone, viscera and soft tissue. The median time from entry on study to progression, for responders, was 15 months. When platinum-DNA adduct formation in peripheral white blood cells was analyzed in 27 patients at 24 h after drug administration, a significant correlation between adduct level and CBDCA cumulative dose was found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450440 TI - Salvage chemotherapy with mitoxantrone and mitomycin with or without methotrexate in advanced breast cancer. AB - Thirty-three patients with advanced and refractory breast cancer were treated with two mitoxantrone-containing regimens (mitoxantrone plus mitomycin and mitoxantrone plus mitomycin plus methotrexate). All patients had received previous chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF); cyclophosphamide, adriamycin and fluorouracil (CAF); or CMF and CAF. Partial response occurred in five patients (15 +/- 12%), stable disease occurred in 15 patients (45 +/- 17%) and progressive disease occurred in 13 patients (40 +/- 17%). The median duration of response was 5 months. The median actuarial survival was 11 months. Toxicity was mild, even in patients who had previously received anthracyclines; generally it was mainly hematological. We thus recommend mitoxantrone-containing regimens as salvage chemotherapy in advanced breast cancer. PMID- 1450441 TI - Mitoxantrone, cytosine-arabinoside and 6-thioguanine (MAT) in the treatment of newly diagnosed acute non-lymphoblastic leukemia in adults. AB - Between January 1986 and September 1989, 28 patients over the age of 14 years were treated with a combination of mitoxantrone, cytosine-arabinoside (Ara-C) and 6-thioguanine (MAT) at the Kuwait Cancer Control Centre (KCCC). All patients were newly diagnosed cases of acute non-lymphoblastic leukemia (ANLL). Fifty-eight courses of treatment were given as induction and consolidation therapy. The main toxicity was bone marrow suppression. Other toxicities were mainly nausea and vomiting, hepatotoxicity, renal dysfunction and alopecia. In most patients these were mild and tolerable. Complete remission (CR) was achieved in 18 out of 28 (64%) patients. In six patients it was achieved after one course, in 11 patients after two courses and in one patient after three courses. The median survival was 16 months and for those who achieved CR it was 33 months. The actuarial 3 year survival following CR was 43% and the relapse-free survival was 24%. There was little difference in the CR rate for patients below 40 years compared with older patients. However, there was a remarkable difference in survival, with none of the older patients surviving more than 2 years and an actuarial 3 year survival for younger patients of 49%. The study confirms the efficacy of the mitoxantrone containing combination as a first-line therapy for ANLL. PMID- 1450442 TI - Salvage cisplatin and adriamycin for advanced or recurrent basal or squamous cell carcinoma of the face. AB - Is it justified to treat a small, localized and relatively indolent malignancy by systemic combined chemotherapy? Five patients with locally advanced skin tumors were treated by salvage cisplatin and adriamycin for three to five courses. Three achieved complete response, one achieved partial response and one succumbed to an unrelated cause. The rapid induction of response, high response rate, unmaintained complete remissions of long duration and relatively low rate of toxicity may justify the use of this combination for the treatment of small skin tumors when other treatment options are of no avail. PMID- 1450443 TI - Inhibition of colon tumor cell growth by 8-chloro-cAMP is dependent upon its conversion to 8-chloro-adenosine. AB - Recent interest in site-selective cAMP analogs has focused on the role of 8 chloro-adenosine (8-Cl-adenosine) in the inhibition of tumor cell growth by 8 chloro-cAMP (8-Cl-cAMP) (Van Lookeren Campagne, et al. Cancer Res 1991; 51: 1600 5). We have evaluated 8-Cl-cAMP and 8-Cl-adenosine for their growth inhibitory activity against two human colon adenocarcinoma cell lines, HCT116 and FET. Because these cell lines have been adapted to grow in chemically defined medium we were able to evaluate the effect of serum on 8-Cl-cAMP's growth inhibitory activity. In addition, cells grown in serum-free medium were tested for their sensitivity to 8-Cl-cAMP, serum-activated 8-Cl-cAMP and 8-Cl-adenosine. IC50 values, determined by measuring cell growth using a MTT colorimetric assay, showed that 'serum activation' of 8-Cl-cAMP was required to achieve inhibition of HCT116 (IC50 = 1.3 +/- 0.1 microM) and FET (IC50 = 2.0 +/- 0.1 microM) cell growth. IC50 values were not reached at the highest concentrations tested (IC50 > 500 microM) in the absence of serum, permitting us to conclude that 8-Cl-cAMP does not have growth inhibitory activity between 1.0 and 500 microM doses. HCT116 and FET cells grown in media containing serum and in the presence of 8-Cl adenosine had IC50 values of 0.6 +/- 0.1 and 0.9 +/- 0.2 microM, respectively. HCT116 and FET cells grown in chemically defined medium containing 8-Cl-adenosine exhibited IC50 values of 1.0 +/- 0.1 and 3.1 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450444 TI - Anti-neoplastic effect of halocynthiaxanthin, a metabolite of fucoxanthin. AB - We have reported that fucoxanthin, a natural carotenoid, inhibited the growth of human neuroblastoma GOTO cells. In the present study, we show that a metabolite of fucoxanthin, halocynthiaxanthin, which is isolated from sea squirt Halocynthia roretzi, has a more potent inhibitory effect. Halocynthiaxanthin (5 micrograms/ml) caused complete suppression of GOTO cell proliferation, whereas fucoxanthin reduced the growth rate by only 88.8% compared with the control, at day 2 after the drug treatment. Furthermore, halocynthiaxanthin also inhibited the growth of other human malignant tumor cells. Thus halocynthiaxanthin seems to be a promising anti-neoplastic agent. PMID- 1450445 TI - Identity of the N-terminal sequences of the three A chains of mistletoe (Viscum album L.) lectins: homology with ricin-like plant toxins and single-chain ribosome-inhibiting proteins. AB - Mistletoe lectin (ML) I increases the production of cytokines by mononuclear cells and has been proposed as a useful biological response modifier in the treatment of cancer. Two other lectins, ML II and ML III, have been identified in mistletoe. We report that the N-terminal sequences of the three A chains of ML I, ML II and ML III are identical, and have interesting homology with the N-terminal sequences of the A chain of ricin-like toxins and of single-chain ribosome inhibiting proteins. In addition, the three mistletoe lectins inhibit the growth of the human tumor cell line Molt 4, ML III being the most potent. followed by ML II and ML I. This inhibition is suppressed by addition of rabbit anti-ML I antibodies to the cultured cells. The data obtained suggest that the three lectins have amino acid sequences which show extensive homology and exert very similar biological effects. They may be derived from the same precursor. PMID- 1450446 TI - Antiproliferative effect of complexes of platinum (II) with plasmanyl-(N-acyl) ethanolamine, an inhibitor of protein kinase C. AB - Antiproliferative activities of combinations of semisynthetic plasmanyl-(N-acyl) ethanolamine [PNAE(s)], an inhibitor of protein kinase C, with two antitumor complexes of platinum (II) [cisplatin and ammine(cyclopentylamine)-S-(-) malatoplatinum (cycloplatam)] were investigated. The exposure of human melanoma BRO cells in culture simultaneously with cisplatin (1-10 microM) and PNAE(s) (100 microM-1 mM) in a molar ratio of 1/100 for 24 h induced a considerable decrease in the ability of these cells to incorporate [3H]thymidine into DNA. A considerable antiproliferative synergism of these agents was observed. The effect of cycloplatam/PNAE(s) combination in similar experiments was significantly different from cisplatin/PNAE(s), i.e. interaction of these agents was complex and synergism was not found. PMID- 1450447 TI - Differential inhibition of proliferation of human squamous cell carcinoma, gliosarcoma and embryonic fibroblast-like lung cells in culture by plant flavonoids. AB - We investigated the antiproliferative effect of two polyhydroxylated (quercetin and taxifolin) and two polymethoxylated (nobiletin and tangeretin) flavonoids against three cell lines in tissue culture. Tangeretin and nobiletin markedly inhibited the proliferation of a squamous cell carcinoma (HTB 43) and a gliosarcoma (9L) cell line at 2-8 micrograms/ml concentrations. Quercetin displayed no effect on 9L cell growth at these concentrations, while at 8 micrograms/ml it inhibited HTB 43 cell growth. Taxifolin slightly inhibited HTB 43 cell growth at 8 micrograms/ml, while moderately inhibiting HTB 43 cell growth at 2-8 micrograms/ml. The proliferation of a human lung fibroblast-like cell line (CCL 135) was relatively insensitive to low concentrations of the above flavonoids. PMID- 1450448 TI - Preclinical activity of hepsulfam and busulfan in solid human tumor xenografts and human bone marrow. AB - Hepsulfam (1,7-heptanediol disulfamate, NSC 329680) is a new antineoplastic alkanesulfonate agent which has demonstrated a broader preclinical activity than busulfan. The compound is currently undergoing clinical trials. We have studied the activity of hepsulfam and busulfan simultaneously in human tumor xenografts in vitro in a clonogenic assay and in vivo in tumor-bearing animals in order to assess the activity of both compounds in model systems of slowly growing malignancies. In a total of 37 different tumors of various histologies, both agents demonstrated broad spectrum in vitro activity. The median IC50 of hepsulfam and busulfan was determined as 0.93 and 3.31 micrograms/ml, respectively. At a concentration of 1.0 micrograms/ml, hepsulfam was active in eight of 37 tumors (22%) in the clonogenic assay, whereas busulfan effected inhibition of colony formation in one of 37 lines (3%). At the same concentration, however, hepsulfam demonstrated a clear in vitro toxicity to human bone marrow cells (CFU-GM) from healthy donors, whereas busulfan did not reveal a myelosuppressive effect. Evaluation of equitoxic concentrations in vitro revealed a higher activity of hepsulfam, especially in non-small cell lung cancer. In tumor-bearing nude mice, the approximate LD10 dose was determined as 150 mg/kg single bolus injection given i.p. on day 1 for both compounds. Hepsulfam demonstrated superior in vivo activity in a large cell lung cancer xenograft and a gastric carcinoma model. The preclinical activity of hepsulfam suggests a possible role of this compound in the treatment of solid human malignancies. However, the increased bone marrow toxicity of hepsulfam as compared with busulfan might be critical for further clinical application.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450449 TI - Curative effects of all-trans-retinoic acid on rat sarcomas. AB - The effects of all-trans-retinoic acid (all-trans-RA) on benzo(a)pyrene [B(a)P] induced malignant sarcomas in Sprague-Dawley female rats were evaluated. Ninety eight days after B(a)P administration, all-trans-RA was daily injected to animals with or without clinically palpable tumors. The growth of tumors was slowed down compared with controls. Magnetic resonance imaging analyses showed that all-trans RA-treated rat tumors presented early necrotic areas. Animal survival was slightly increased. Anti-phosphatidylinositol autoantibody levels which were significantly higher in B(a)P-treated rat sera were not modified by all-trans-RA treatment. PMID- 1450450 TI - Identification of 3,4-dihydroxyphenylalanine, 5,6-dihydroxyindole, and N acetylarterenone during eumelanin formation in immune reactive larvae of Drosophila melanogaster. AB - 3,4-Dihydroxyphenylalanine, 5-6-dihydroxyindole, and N-acetylarterenone were detected by electrochemical methods in the hemolymph of immune reactive larvae of Drosophila melanogaster following parasitization by the wasp Leptopilina boulardi. Determinations of the catechols were made after separation by reverse phase, ion-pairing high pressure liquid chromatography with electrochemical detection. The presence of 5,6-dihydroxyindole unequivocally establishes the eumelanin pathway in the defense response of Drosophila, and confirms previous investigations which have implicated certain catecholamine metabolizing enzymes in insect immunity. The occurrence of N-acetylarterenone, a derivative of the principal sclerotizing agent N-acetyldopamine, verifies the existence and proposed involvement of quinone methide isomerase in the regulation of catecholamine metabolism, and suggests that the cellular capsule formed by Drosophila in immune reactions against parasites is most likely a composite of both eumelanin and sclerotin. The absence of 3,4-dihydroxyphenylacetic acid in hemolymph samples from immune reactive hosts suggests that during parasitization certain catecholamines and metabolic precursors may be re-employed in alternate pathways, some of which may be used in defense reactions. PMID- 1450451 TI - A FMRFamide-like peptide is associated with the myotropic ovulation hormone in Rhodnius prolixus. AB - The protocerebral neurosecretory cells previously shown to be the source of the myotropin controlling ovulation in Rhodnius prolixus react in an immunocytochemical assay using an antiserum against FMRFamide. When the same antiserum was injected into fed mated females at the appropriate time the timing of oviposition was delayed, but the total number of eggs developed was unaffected compared to controls injected with pre-immune rabbit serum. The titer of FMRFamide-like peptide (assayed by RIA) in the hemolymph of mated and virgin females was found to fluctuate with the egg laying cycle, and to reflect earlier determinations of the titer of myotropic activity. Western blots of SDS-PAGE revealed a FMRFamide-immunoreactive peptide of approximately 8.5 kDa in both hemolymph and extracts of the ovulation hormone cells. PMID- 1450452 TI - The gonad of the desert snail Eremina ehrenbergi Roth, 1839 (Stylommatophora Gastropoda) and its role in the production of the male gametes. AB - Specimens of Eremina ehrenbergi Roth, 1839, were collected in the El-Omayed area of the Sahara Desert, west of Alexandria. This simultaneously hermaphrodite snail has a comparatively small gonad enclosed in a thin membrane. The gonad is composed of a mass of branched tubules, each differentiated to a generative proximal half and a conducting distal half. The primitive germ cells proliferate from germinal cells forming a discontinuous layer in the germinal wall of each tubule; they undergo spermatogenesis or oogenesis at the original site of their proliferation. A cluster of spermatogonia may be derived from one primitive germ cell and it develops round a "Sertoli" cell. The division and differentiation of the cells in each cluster are strictly synchronized. The role of the gonad in formation of the spermatophore is restricted to the production of clusters of mature spermatozoa, which are discharged, without the "Sertoli" cell, via three efferent ductuli connecting the conducting portions of the gonadal tubules with the hermaphrodite duct. The sperm has the same appearance as in vertebrates and can be studied in smears prepared from the gonad or the middle of the hermaphrodite duct, where they are collected and stored for a time. PMID- 1450454 TI - Development of medical genetics in the Czech Republic from 1986 to 1990. PMID- 1450453 TI - A study of the formation of the neural network in the lungs of Perdicula asiatica, as revealed by the cholinesterase technique. AB - The investigation was undertaken to investigate the formation and association of neural network and their fibres with nerve cells and ganglia in the parenchyma. The staining of the neural network was done by the cholinesterase technique under the maintained pH 5.2, temperature 40 degrees C and incubation period 30 hrs. The neural network was formed by a good number of tortuous thick nerves and was related either with nerve cells or ganglia. At times, it was formed by a good number of thick nerves and a few thin nerves in the connective tissue space. PMID- 1450455 TI - Ethical aspects of genetic counselling. PMID- 1450456 TI - Preclinical diagnostics for polycystic kidney disease. PMID- 1450457 TI - Clinical and cytogenetical findings in five patients with the Prader-Willi syndrome. PMID- 1450458 TI - Prenatal diagnosis of congenital nephrotic syndrome of Finnish type. PMID- 1450459 TI - Ultrasonographic and biochemical markers in prenatal detection of Down's syndrome and neural tube defects. PMID- 1450460 TI - Haplotype analysis of the CFTR gene region and the proportion of delta F508 deletion in Slovak patients with cystic fibrosis. PMID- 1450461 TI - Histoenzymological demonstration of glycerol-3-phosphate dehydrogenase and succinate dehydrogenase in the telencephalic nuclei and fibre tracts of hillstream cyprinoid, Barilius bendelisis (Hamilton). AB - The authors studied the regional localization of two dehydrogenases--glycerol-3 phosphate dehydrogenase and succinate dehydrogenase--in the telencephalic nuclei and fibre tracts of Barilius bendelisis by histoenzymological methods. The activity of these dehydrogenases varied from moderately positive to strongly positive in the nuclear areas and from intensely to strongly positive in the fibre tracts, except those related to the olfactory tubercle. G3PD appears to play an important role in the biosyntheses of phospholipids and to form a link between glycolysis and the pathway of the hexose-monophosphate shunt, in addition to its usual role in the degradation of glucose, along with other dehydrogenases, including succinate dehydrogenase. PMID- 1450462 TI - Studies of the histoenzymological mapping of acid and alkaline phosphatases in the hindbrain of Barilius bendelisis (Hamilton). AB - The regional localization of acid and alkaline phosphatase (EC 3.1.3.2. and 3.1.3.1. respectively), determined histoenzymologically, is described in the cerebellum and medulla oblongata of Barilius bendelisis (Hamilton). Acid phosphatase activity in nuclear areas was observed to be moderately positive, whereas alkaline phosphatase activity varied from weak to strongly positive. The localization pattern of these enzymes in the fibre tracts differed. One interesting finding in this study was that the Purkinje cells in the cerebellum and the Mauthner cells in the medulla oblongata contained these enzymes in a high concentration. The contrasting cytological distribution patterns of the two enzymes indicate that their roles in the neurons and fibre tracts are probably different. PMID- 1450463 TI - Wallagotrema indicus n.sp., a new monogenean from the freshwater sheat-fish Wallagu attu Bloch and Schneider. AB - The paper describes Wallagotrema indicus n.sp., a freshwater monogenean recovered from the gill filaments of the freshwater sheat-fish Wallago attu Bloch and Schn. It is characterized by the number of head organs, an accessory piece on the cirrus, wings on the anchors and a beak-like outgrowth on the dorsal anchors, together with numerous other differences in the shape and size of various body parts. On the basis of these findings, the generic diagnosis of Wallagotrema is amended and a key to the various species of this genus is appended. PMID- 1450464 TI - Variability of the v. cava caudalis and its tributaries in some laboratory animals. II. The laboratory rat (Rattus norvegicus v. alba). AB - Duplication of the v. renalis was found in 11 of the regions examined (18.3%), when it was more frequent on the right side. A v. capsularis was found in 35 regions (58.3%), usually as a single vein. There were 1-3 vv. suprarenales (but mostly two; on the right they usually joined the v. cava caudalis and on the left the v. renalis sinistra). A v. spermatica was present on the right side in every case, but on the left side in 11 cases only; in one case it was duplicated. In the rat, the v. spermatica was rather thin; if absent, it was replaced by the v. deferentialis. In nine cases (60.0%) the v. uterina cranialis dextra opened into the v. cava caudalis, while in 12 cases (80.0%) the left vein opened into the v. renalis sinistra. A v. uterina media, draining blood from the caudal third of the cornu uteri, was found in only five cases (16.7%). The v. uterina caudalis drained blood from the corpus and cervix uteri. The v. ovarica was a constant finding; it was mostly joined by the v. lumbalis--and on the left side by the v. phrenica sinistra. In males, the vv. lumbales occurred mostly as a pair of veins lying just below the vv. renales. In females, they were present on both sides. As a rule, the v. iliolumbalis occurred as a single vein on both sides. The v. cava caudalis originated at the level of the transition between the lumbar and the sacral spine, usually at the confluence of the two vv. iliacae communes, which in 14 cases (46.7%) were joined by the v. sacralis mediana. Duplication of the v. cava caudalis was found in only one case (a female). Comparison of the morphology of the v. cava caudalis and its tributaries in the rat and the guinea pig showed more slight differences between the two species. PMID- 1450465 TI - Effect of testosterone on the ovotestis of the land snail Theba pisana. AB - The effect of testosterone on the histological pattern of the gonads of the land snail Theba pisana was studied. It was found that testosterone accelerated spermatogenesis, as indicated by the large increase in the number of spermatozoa and the decrease in the number of primary spermatocytes. The diameter of the acini in treated snails was greater than in the normal controls. Conversely, testosterone led to reduction of the number of mature ova. PMID- 1450466 TI - Current strategies for vascular access in patients on hemodialysis. PMID- 1450467 TI - What we have learned about uremia from peritoneal dialysis. AB - Weekly clearances of small solutes such as urea are relatively low on continuous ambulatory peritoneal dialysis (CAPD) compared to those of thrice weekly hemodialysis (HD); large solute clearances are more comparable. Some believe that good clinical outcomes with chronic peritoneal dialysis support the importance of larger molecular weight toxins. However, CAPD patients of large size or approaching an anephric state occasionally develop uremic symptoms that can be reversed with an increased exchange volume or an increased number of exchanges. Increasing exchange volume or the number of exchanges increases small solute clearances by an amount near the increase in drain volume, but clearances of larger molecular weight substances are minimally affected. Thus, peritoneal dialysis experiences initially focused attention on large molecules and now appear to confirm the importance of small solutes in uremic toxicity but at lower clearance requirements than needed in HD. PMID- 1450469 TI - Recent research in extracorporeal life support for respiratory failure. PMID- 1450468 TI - ECMO in the management of cardiac failure. AB - Extracorporeal membrane oxygenation (ECMO) can provide univentricular or biventricular cardiac, as well as respiratory, support; it has extended the application of ECMO to infants and children who develop refractory cardiogenic shock before or after repair of congenital heart defects. The Pediatric Cardiac ECMO Registry, recently established by the Extracorporeal Life Support Organization, reports an overall survival rate of 47%. All were believed to have little chance of survival without mechanical support. ECMO has also been used for perioperative cardiac support after cardiac transplant. Hemorrhage remains the most common complication of ECMO. The future of ECMO for cardiac support depends on development of methods to prevent cardiac failure, improved ECMO techniques, and increased pediatric cardiac transplantation. PMID- 1450470 TI - Implantable pumps. Recent progress and anticipated future advances. AB - The implantable pump field is now more than 20 years old. The original goal of developing a totally artificial beta-cell remains unrealized, but programmable insulin pumps that contain all of the elements of the artificial beta-cell except the glucose sensor are involved in clinical trials in the United States and are commercially available in Europe. Currently, both single-rate and programmable implantable pumps are in general clinical use in the United States for the treatment of pain and spasticity, cancer, and osteomyelitis. Only a few of the potential applications of implantable pumps have been developed to the stage of commercial availability. This is, in part, because drug companies have traditionally developed parenteral drug applications only as a last resort and, in part, because of the complexity of the regulatory process for implantable pumps, often requiring review by both the drug and device branches of the Food and Drug Administration. PMID- 1450471 TI - Effects of the Berlin Heart biventricular assist device on microvascular responses in pre-transplant patients. AB - Microcirculatory forearm cutaneous blood flow was monitored continuously and noninvasively by laser doppler flow-metry (LDF) in 15 patients treated with the Berlin Heart biventricular assist device system (BVAD) for end-stage heart failure under stable hemodynamic states (BVAD pts, n = 10) and norepinephrine therapy (BVAD nor pts, n = 5). Ten healthy human subjects served as controls (C). Cutaneous blood flow was measured before, during, and after external brachial artery occlusion to evaluate the post-occlusive reactive hyperemia (PORH) as a standardized response. To examine microvascular responses to macrohemodynamic changes, the cardiac output (CO) was decreased by a 20% reduction in BVAD pump rate. No significant differences in baseline LDF measurements (in millivolts) were observed among the three groups (C, 470.7 mV +/- 177.3; BVAD pts, 328.0 mV +/- 122.7; BVAD nor pts, 360.0 mV +/- 160.0). After cuff pressure release (1 min later), a significant (p < 0.004) three-fold to four-fold blood flow increase (PORH) occurred in each group (C, 1113.6 mV +/- 469.2; BVAD pts, 813.0 mV +/- 190.1; BVAD nor pts, 498.0 mV +/- 191.8). The difference in PORH between the BVAD pts and BVAD nor pts was significant (p < 0.01), and the time to peak PORH values was different (p < 0.05) among the three groups (C, 22.2 s +/- 10.7; BVAD pts, 11.3 s +/- 12.5; BVAD nor pts, 7.0 s +/- 5.8). A markedly delayed return to baseline occurred in the BVAD pts. The 20% reduction in BVAD pump rate decreased CO significantly (p < 0.05) and increased (p < 0.01) systemic vascular resistance (SVR).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450472 TI - Simple membrane models for peritoneal dialysis. Evaluation of diffusive and convective solute transport. AB - Currently used mathematical models to estimate parameters describing diffusive (diffusive mass transport coefficient, KBD) and convective (sieving coefficient, S) solute transport during peritoneal dialysis, as proposed by Pyle, Popovich, and Moncrief (PPM model) and Babb, Randerson, and Farrell (BRF model), require nonlinear regression and advanced numerical methods for parameter estimation. In this study, a simplified approach to the evaluation of KBD and S, using the same transport equation used in the PPM and BRF models but based on two-dimensional linear regression, is proposed. This new approach can be extended to generate a family of membrane models that differ in assumption concerning the average solute concentration (c) inside the peritoneal membrane. In particular, c was assumed to be equal to the arithmetic mean value of the dialysate and blood concentrations (PPM model), the blood concentration (BRF model), or the dialysate concentration (D model). The investigated family of models was used to study the transport of urea, creatinine, glucose, sodium, potassium, and total protein in 20 single, 6 hr dwell studies carried out in 20 nondiabetic patients in stable clinical condition using hypertonic (3.86%) glucose solution. For the PPM model, the linear and nonlinear regressions were able to provide almost identical values of KBD and S. The theoretical dialysate to plasma concentration ratio (D/P) was adequately fitted to experimental D/P for both the PPM and BRF models, but the fit was worse for the D model. However, unphysiologic (i.e., out of the 0-1 range) values of S were found for urea, potassium, and glucose independent of the version of the model used. PMID- 1450473 TI - Oxalate removal by differing dialysis techniques. AB - Secondary hyperoxalemia is a common feature in patients with chronic renal failure, but oxalate removal is not adequately accomplished by regular dialysis treatment. Oxalate removal in two groups of patients, 11 on continuous ambulatory peritoneal dialysis (CAPD) and 12 on hemodialysis (HD), was investigated. HD patients were studied during a regular bicarbonate dialysis and during hemodiafiltration (HDF) with a high convective component (UF = 66 mL/min) and AN69 filter (Hospal Filtral 12, 1.2 m2, Hospal Industrie, Meyzieu, France). All HD and HDF spent dialysate and all 24 hr CAPD effluents were collected; oxalate concentration was measured by high performance liquid chromatography (HPLC) using an ion exchange column. Both oxalate flux and total extraction were statistically higher during HDF treatments (HDF = 1.87 +/- 0.77 mg/min and 335.9 +/- 131.5 mg/session, respectively; HD = 0.99 +/- 0.74 mg/min, 226 +/- 153 mg/session, respectively; p < 0.02). The positive interaction of convective and diffusive fluxes probably played a major role in oxalate removal during treatment with a high convective component; solute-membrane interactions can occur by using either cellulosic or synthetic fibers. In CAPD patients, oxalate removal (76.42 +/- 50.85 mg/day) was lower than in patients on either HD or HDF, although weekly oxalate extraction was statistically no different between CAPD (535.46 +/- 356 mg/week) and HD (677.72 +/- 460.82 mg/week). It was concluded that HDF is more effective than HD or CAPD in oxalate removal. Long-term studies are needed to demonstrate whether these kinetic findings have clinical relevance. PMID- 1450474 TI - Where should the hemofiltration circuit be placed in relation to the extracorporeal membrane oxygenation circuit? AB - Patients requiring extracorporeal membrane oxygenation (ECMO) frequently experience hypervolemia and metabolic abnormalities that can be effectively managed by hemofiltration. Although several options for hemofiltration circuit placement exist, some may have the disadvantage of recirculation or shunting of poorly oxygenated blood to the patient. Attachment of the entire hemofiltration circuit to the pre-ECMO pump region is described. Despite the absence of pump generated pressure and a low blood flow rate, effective hemofiltration and diafiltration were achieved. This article examines whether placement of the hemofiltration circuit proximal to the ECMO pump has advantages over other hemofiltration circuit placements. PMID- 1450475 TI - Current functional status of Symbion total artificial heart recipients after transplantation. AB - This multicenter study examines long-term data from the five most experienced North American centers (> 8 total artificial heart [TAH] implants), investigating the functional status of 37 patients who received a Symbion TAH followed by a heart transplant (TX) with post-TX survival > or = 1 year. Primary indications for TAH use included acute cardiogenic shock in 38% (14/37) of patients and deterioration while on the TX waiting list in 35% (13/37). At the time of this study, 86% (32/37) of patients were alive, 94% of whom were functioning at a New York Heart Association (NYHA) classification of I (75% [24/32]) or II (19% [6/32]). NYHA classification before death was I for all five patients who died 40 +/- 17 (r = 14-58) months after transplant. Of the 32 surviving patients, 47% (15) were working, 16% (5) were retired, 12% (4) chose not to work, and 9% (3) were in school. The remaining 16% (5) were unable to work due to surgical limitations. After TX, significant infections occurred in 81% (26/32) of patients and rejection in 72% (23/32). At 1 year after TX, creatinine was within normal limits (< or = 1.4 mg/100 ml or 65-125 mol/L) for 41% (13/32) of patients, 1-2 times normal for 56% (18/32), and > 2 times normal for 3% (1/32). Although TAH is not required for most patients awaiting TX, the device allows excellent long-term functional status in patients otherwise at risk for death. No long-term problems related to the use of temporary mechanical circulatory support were found. PMID- 1450476 TI - Accuracy of intravenous infusion pumps in continuous renal replacement therapies. AB - Most extracorporeal continuous renal replacement therapies (CRRT) require inflow pumping of either dialysate, filtrate replacement solution, or both. Outflow of spent dialysate and ultrafiltrate can be accomplished by gravity drainage or pump. Intravenous infusion pumps have been commonly used for these purposes, although little is known about the accuracy of these pumps. To evaluate accuracy of two different types of intravenous infusion pumps used in CRRT, we studied flow rates at nine different pressure variations in three piston type and three linear peristaltic pumps. The results showed that error of either pump was not different for flow rates of 4 and 16 ml/min. Both types of pumps were affected by fluid circuit pressures, although pressure conditions under which error was low were different for each pump type. The linear peristaltic pumps were most accurate under conditions of low pump inlet pressure, whereas piston pumps were most accurate under conditions of low pump pressure gradient (outlet minus inlet) of 0 or -100 mmHg. The magnitude of error outside these conditions was substantial, reaching 12.5% for the linear peristaltic pump when inlet pressure was -100 mmHg and outlet pressure was 100 mmHg. Error may be minimized in the clinical setting by choosing the pump type best suited for the pressure conditions expected for the renal replacement modality in use. PMID- 1450478 TI - Effect of endotoxin clearance using whole body rinse-out on some blood-gas and metabolic parameters in rats. AB - Conscious and unrestrained male Wistar rats were infused over a 10 min period with 60 mg/kg Escherichia coli endotoxin (LD100) and observed for 6 hr. Hypotension, metabolic acidosis, hyperlactemia, hypoglycemia, and elevated oxygen extraction from blood developed in the rats. Another group of rats was subjected to blood substitution with FC-43 emulsion (artificial blood) 30 min after endotoxin application until hematocrit dropped to 3%, after which 6-9 ml of donor blood was exchange transfused with the emulsion. This method resulted in 98% endotoxin clearance, improved blood alkaline reserves, preserved blood glucose, and normalized arterial mixed venous oxygen gradient and O2 extraction from the blood (which implies preserved blood circulation status). Side effects included hypotension, a transitory rise in blood lactate level, and a fall in arterial oxygen content due to the lower hemoglobin (erythrocyte) level. PMID- 1450477 TI - Disordered breathing patterns during bicarbonate hemodialysis in COPD. Effect of cuprophane versus polysulfone membranes. AB - This study explored the breathing patterns and arterial blood gases before and during cuprophane (CU) bicarbonate and polysulfone (PS) bicarbonate dialysis in six chronic dialysis patients with mild chronic obstructive pulmonary disease (COPD). The studies were performed in random order during two consecutive dialyses. Breathing patterns were monitored by respiratory impedance plethysmography. Apneic episodes, defined as a decrease in tidal volume of 75% lasting 10 sec, were present before and during hemodialysis. In these patients with COPD a high number of apneic episodes (17 +/- 6 [SE]) were observed during CU bicarbonate hemodialysis. Most of these episodes were central rather than obstructive in character. There were fewer events when the same patients were dialyzed with PS membranes (10 +/- 5; p = 0.05). The decrement in PO2 (baseline to 60 min) was 17 +/- 7 during CU and 4 +/- 5 mmHg during PS dialysis (p = 0.10). Minute ventilation decreased in four of six patients on CU bicarbonate and increased in all six patients on PS bicarbonate. It was concluded that bicarbonate hemodialysis does not completely prevent hypoxemia or apnea during dialysis in patients with COPD. Apneic episodes and hypoxemia appear to be less severe during PS bicarbonate than during CU bicarbonate hemodialysis. PMID- 1450479 TI - Prevention of hemodialysis associated hypoxemia by use of low-concentration bicarbonate dialysate. AB - Hypoxemia during acetate dialysis is caused by hypoventilation due to bicarbonate loss across the dialyzer and its regeneration from acetate by a CO2 consuming process. Loss of bicarbonate is prevented by using a bicarbonate containing dialysate, but hypoxemia is still found by many authors. In the current study, ten patients were dialyzed twice against acetate dialysate, high concentration bicarbonate (36 mmol/L), and low concentration bicarbonate (29 mmol/L) dialysates. A significant decrease in PO2 was found during both acetate and high concentration bicarbonate dialysis. Hypoxemia was prevented by low concentration bicarbonate dialysate. A possible explanation for the hypoxemia in high concentration bicarbonate dialysis may be hypoventilation induced by alkalosis. It was concluded that low concentration bicarbonate dialysate prevents hypoxemia during hemodialysis. PMID- 1450480 TI - Peritoneal transfer of carbon dioxide in the rat. AB - In the authors' previous rat studies (Kidney Int 39: 608-617, 1991), peritoneal clearances (Cp) representing near exclusively diffusive CO2 transfer were evaluated: for isosmotic (0.37% dextrose) and hyperosmotic (15% dextrose) solutions with pH 7.2-7.3, Cp CO2 were 1.20 +/- 0.08 and 1.84 +/- 0.04 ml/min, respectively. In the present studies peritoneal transfer parameters (D/B, Cp) of CO2 gas, HCO3-, and total CO2 (tCO2) in anesthetized rats have been compared (n = 22) using solutions with dextrose contents as mentioned above but with a pH of 6.5 or 7.6; how much Cp CO2 measurements obtained with solutions at these pH values differ from Cp shown earlier with solutions of pH 7.2-7.3 has also been evaluated. When the pH was the same, transfer parameters of CO2 gas, HCO3-, and tCO2 were significantly higher under hyperosmotic conditions. The use of solutions with a pH different from 7.2-7.3 resulted in higher Cp of CO2 gas: with isosmotic solutions at pH 6.5 and 7.6, mean increases were 25 and 75%, respectively; with hyperosmotic solutions respective increases were 45 and 134%. The authors conclude that dialysis solution pH, especially under hyperosmotic conditions, significantly changes parameters of diffusive CO2 transfer in the rat. For evaluation of peritoneal blood flow from diffusive transfer parameters of CO2 gas, smaller overestimation can be expected when dialysis solution pH is slightly under than overadjusted compared to blood pH. PMID- 1450481 TI - Influence of aspirin and carbacyclin on bovine platelet function. AB - Cows, calves, and sheep are the animals of choice for in vivo studies on total artificial hearts. In this study, the response of human and bovine platelets to agonists and antagonists was followed. Epinephrine and arachidonate failed to cause aggregation of bovine platelets. Exposure of bovine platelets to prostaglandin E1 (PGE1) resulted in inhibition of response to the action of adenosine diphosphate (ADP). Although epinephrine restored the response of PGE1 treated human platelets, it failed to restore the sensitivity of bovine platelets to the action of ADP. Exposure of bovine platelets to aspirin (100.0 mumol/L) or administration to calves intravenously (10.0 mg/kg) inhibited platelet cyclo oxygenases. Infusion of carbacyclin (U55185) inhibited the ex vivo platelet response to the action of ADP. Results of this study demonstrate that the response of bovine platelets to agonists such as epinephrine, arachidonate, and the endoperoxide mimetic, U46619, is severely compromised. The authors' observations in this study, as well as earlier findings demonstrating the inability of bovine platelets to fully spread on a surface, suggests that the cow may not be an appropriate "model" for evaluating thrombogenicity caused by artificial organs and implants. PMID- 1450482 TI - Comparison of a new venous control device with a bladder box system for use in ECMO. AB - During extracorporeal membrane oxygenation (ECMO), forward pump flow must not be allowed to exceed the rate of blood drainage from the patient so that excessive negative pressure does not develop within the ECMO circuit or in the patient's right atrium. A distensible reservoir ("bladder") and mechanically actuated electronic switch ("bladder box"), has typically been used for this purpose. If the rate of blood flow from the patient to the pump is insufficient to support the perfusion rate desired and adjustments in volume status and catheter position do not increase blood drainage, the only recourse is to increase the siphon pressure by elevating the patient. At the author's institution, a novel venous control module (VCM), without a reservoir, that can provide increased venous drainage without elevating the patient is used. Using an in vitro model of neonatal ECMO, the authors' compared their VCM to a commercially available "bladder box" system. Pressures were monitored in a collapsible chamber inside a water bath (simulating the right atrium), at the gravitational high point of the ECMO circuit ("neck site") and at the low point of the circuit ("venous site") at flow rates of 100, 450, 900, and 1,300 cc/min. Pump shut-off characteristics for both systems were also measured with either sudden interruption of venous drainage ("cross-clamping") or restriction of venous inflow ("hypovolemia"). Under continuous flow conditions, higher flows could be achieved with the VCM. With acute venous catheter occlusion, instantaneous ("trough") pressures at the neck site were lower, and venous monitoring site pressures were higher with the bladder box system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450483 TI - Hepatocytes from rat liver perfusions. Physicochemical effects on polyribosome size. AB - Hepatocytes have been used extensively both in vitro and in vivo for a wide variety of studies. Although isolated hepatocytes appear similar to their in vivo counterparts, they are different in some respects. One aspect in which they differ is their ability to translate proteins. The isolation process appears to inflict sufficient damage to reduce the average polyribosome size within the isolated hepatocytes and this size reduction correlates with a lower rate of protein production. Two methods of liver perfusion that better maintain the normal distribution of polyribosomes are described in this report. It is clear from these studies that new isolation methods that result in high yields of viable hepatocytes that function maximally are needed. PMID- 1450484 TI - Cardiac output regulation in the moving actuator total artificial heart without a compliance chamber. AB - A new cardiac output regulation method for the moving actuator total artificial heart (TAH) has been developed without using an extra compliance chamber or any transducer. The left and right ventricular sacs are alternately pumped by the pendulous moving actuator, with the left sac attached to the actuator and a free right ventricle. Preload sensitive cardiac output response is achieved by adjusting heart rate just below the level needed to generate atrial collapse, while maintaining full-fill and full-ejection conditions. The motor current waveform analysis detects mild atrial suction related to the amount of venous return. In addition, the structural characteristic of the pendulous moving actuator allows for manipulation of the left and right ventricular output difference by adjusting the asymmetry of stroke angle to either the left or right. In mock circulatory system tests, cardiac output increased from 5 to 9 L/min, with left atrial pressure (LAP) maintained at approximately 5 mmHg higher than right atrial pressure (RAP) over a physiologic range of preload (0-12 mmHg of RAP) and afterload [80-120 mmHg of aortic pressure (AoP)]. PMID- 1450485 TI - Glucose-insulin kinetics of the extravascular bioartificial pancreas. A study using microencapsulated rat islets. AB - The success of the extravascular bioartificial pancreas (BAP) is contingent on the rapid transfer of the glycemic signal across both an extravascular compartment and a semipermeable membrane and of insulin from the BAP to the recipient. To examine the possibility of microencapsulated islets such as the BAP to achieve satisfactory in vivo glucose-insulin kinetics, islets were isolated from Lewis rats, encapsulated in poly-L-lysine-alginate membranes, and isogenically transplanted into the peritoneal cavity of 14 streptozotocin induced diabetic rats. Fasting blood glucose (BG) was measured and intravenous glucose tolerance was tested at 8-10 weeks and compared with three control groups: 1) normal Lewis rats (n = 6); 2) untreated diabetic rats (n = 5); and 3) diabetic rats that received intraperitoneal implants of empty capsules (n = 4). Ten animals that received microencapsulated islets (5,271 +/- 431) promptly became normoglycemic, with a mean BG of 128 +/- 17 ng/dl 3 days after transplantation and maintained this level > 100 days. Intravenous glucose tolerance K-value for the group was 3.84 +/- 0.32 compared with 3.96 +/- 0.39 (p = 0.83) for the normal control group, and 0.60 +/- 0.12 (p < 0.01) and 0.40 +/- 0.15 (p < 0.01) for the diabetic control groups with and without empty capsules. The authors conclude from these results that, given sufficient beta-cell mass, a BAP without any vascular access can respond appropriately to an increase in blood glucose concentration, without overshoot hypoglycemia and within a lag lapse compatible with normal physiologic insulin delivery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450486 TI - Administration of GSH has no influence on the RBC membrane: oxidative damage to patients on hemodialysis. AB - In patients on hemodialysis, a metabolic block of the pentose phosphate shunt has been described that impairs the reduction of oxidized glutathione. The block results in lack of detoxication of the free hydroxyl radicals produced inside the red blood cell (RBC) and causes oxidative damage to the polyunsaturated fatty acids of the RBC membrane that results in formation of aldehydes. Malonyldialdehyde has been used as an index of the oxidative damage. In a study group of 13 patients on hemodialysis, the authors have tested whether administering reduced glutathione (GSH) at 1200 mg/day for 1 month could minimize oxidative damage to the RBC membranes and improve the hematologic parameters. Treatment with GSH was followed by significant improvement of hematocrit (P = 0.008), hemoglobin (P = 0.03), and RBC count (P = 0.0037); however, oxidative damage to the membranes was increased (P = 0.0004), which suggests that improvement of the hematologic parameters is not related to reduction of the oxidative damage. This is because oxidized glutathione, formed in the oxidative process, cannot be reduced back to GSH because of alteration of the pentose phosphate shunt. PMID- 1450487 TI - Identification and certification of extracorporeal membrane oxygenation specialists in the United States. AB - Extracorporeal membrane oxygenation (ECMO) is a highly specialized technique widely practiced in many hospitals. Despite the proliferation of ECMO, little information has been generated relating to ECMO specialists, a new professional group responsible for managing the extracorporeal life support (ELS) system. A telephone survey of ECMO centers in the United States was conducted to determine the number of ECMO specialists, team composition by profession, and clinical components of ECMO specialist certification. Data were obtained in May 1991 from all 63 (100%) active ELS centers. The survey found that the average ECMO program performs 3,770 +/- 1,019 clinical hours of ELS per year with a team of 23 +/- 11 specialists. There are 1,431 practicing ECMO specialists in the United States: 73% registered nurses, 22% respiratory therapists, and 5% others. Most ECMO specialist teams (56%) are comprised of a single profession, with 44% of programs using a mixture of professions. The average ECMO specialist manages the ELS system 171 +/- 91 hr/yr. Thirty-six (57%) programs have a mean yearly clinical requirement of 77 +/- 23 ELS hours per specialist. These results represent the first complete report identifying the number of ECMO specialists in the United States. In addition, program demographics demonstrate variability in ECMO experience and certification requirements. PMID- 1450488 TI - Intra-aortic balloon rupture. An increasing trend? PMID- 1450489 TI - Influence of recombinant interleukin-2 and tumor necrosis factor-alpha on the development of ethyl nitrosourea-induced brain tumors. AB - Using the experimental model of brain tumors induced by ethyl-nitrosourea (ENU), human recombinant interleukin-2 (rIL-2) and tumor necrosis factor-alpha (TNF alpha) were administered to Wistar rats in early stages of carcinogenesis. The results obtained suggest that IL-2 does not influence the development of nervous system tumors. In contrast, TNF-alpha was capable of modulating the development of ENU-induced tumors, producing a reduction in the number of schwannomas and a delay in the appearance of intraparenchymatous brain tumors. PMID- 1450490 TI - HL-60 cells isolated for resistance to vincristine are defective in 12-O tetradecanoylphorbol-13-acetate induced differentiation and the formation of a functional AP-1 complex. AB - HL-60 cells isolated for resistance to vincristine are multidrug resistant and defective in the cellular accumulation of drug. Further studies demonstrate that these cells are also highly defective in 12-O-tetradecanoylphorbol-13-acetate (TPA) induced differentiation to macrophages. Analysis of this system demonstrates that certain protooncogenes which may contribute to differentiation are expressed at similar levels in sensitive and resistant cells. Thus, treatment of cells with TPA results in a reduction in the levels of c-myb and c-myc mRNA, while the expression of c-fos, c-jun, and junB is greatly enhanced. Immunoprecipitation experiments also demonstrate a TPA induced increase in the c jun protein in both sensitive and resistant cells. Gel mobility shift assays show that TPA induces AP-1 formation in sensitive cells, whereas in parallel experiments with the HL-60/Vinc isolate, AP-1 is essentially absent. It has been found, however, that in resistant cells which have reverted to drug sensitivity, the levels of TPA inducible AP-1 is essentially identical to that of sensitive cells. Revertant and sensitive cells differentiate at similar levels in the presence of TPA. These studies therefore demonstrate that HL-60/Vinc cells are defective in the TPA induction of a functional AP-1 complex and that this may account for the inability of these cells to differentiate to macrophages. The molecular basis of the finding that AP-1 is not formed in resistant cells remains to be determined. PMID- 1450491 TI - Measurement of folylpolyglutamate synthetase activity in head and neck squamous carcinoma cell lines and clinical samples using a new rapid separation procedure. AB - The activity of folylpolyglutamate synthetase was measured in extracts of head and neck squamous carcinoma cell lines and in surgical specimens utilizing a new rapid method to separate free [3H]glutamate from [3H]glutamate incorporated into methotrexate, used as a substrate for the enzyme. The validity of this new method, based on reversed phase chromatography via a Sep-Pack C18 cartridge, was observed between both methods, but the Sep Pack C18 assay has the advantage that it can be accomplished in less than 5 min, whereas the DE-52 procedure requires approximately 2 hr. In seven head and neck cell lines, activity of folylpoly glutamate synthetase varied from 335-1305 pmol [3H]glutamate incorporated/mg protein/hr. In nine head and neck tumor biopsies, a broad range in activity of folylpolyglutamate synthetase was observed (25-1827 pmol/mg/hr) which partly overlapped the enzyme activity in 'normal' tissue (7-297 pmol/mg/hr). For six patients, folylpolyglutamate synthetase was measured in the center of the tumor, in the transitional region from tumor to 'normal' tissue, and in the 'normal' tissue. The enzyme activity was higher in tumor tissue vs 'normal' tissue in four of six cases, whereas in all cases, the enzyme activity in the transitional region was higher than in 'normal' tissue. The results of this study provide further support for the concept that putative differences in folylpolyglutamate synthetase activity between tumor tissue and normal tissue can be exploited to improve the effectiveness of antifolate-based chemotherapy in general, and in head and neck cancer in particular. PMID- 1450492 TI - Therapeutic trials on progressive muscular dystrophy. AB - The special medical care in the National Sanatorium prolonged the life span of the patients with progressive muscular dystrophy from 15.8 years to 20.4 years over the last 20 years. Various new drug trials for muscular dystrophy have been implemented in the last 12 years in Japan. Bestatin and Loxistatin, protease inhibitors, showed definite improvement on dystrophic mice or hamsters, animal models of muscular dystrophy. However clinical application of these drugs failed to prove the effects on patients with Duchenne muscular dystrophy. The difficulty of clinical evaluation and judgement of effects in progressive neurological diseases is discussed. PMID- 1450493 TI - Acute and chronic eosinophilic pneumonia: clinical evaluation and the criteria. AB - The clinical courses of 11 cases of eosinophilic pneumonia which were clinico pathohistologically diagnosed and found to be unassociated with organic disorders producing peripheral blood eosinophilia were extensively investigated and compared with various types of eosinophilic pneumonia previously reported. Five cases of acute eosinophilic pneumonia fulfilled the following criteria: 1) less than a one-month history of symptoms prior to diagnosis, 2) a short clinical course and 3) no recurrence. Six cases of chronic eosinophilic pneumonia fulfilled the following criteria: 1) more than a two-month history of symptoms prior to diagnosis, 2) a prolonged clinical course and 3) recurrence. The results suggested that various types of previously reported eosinophilic pneumonia classified by sex, the presence or absence of peripheral blood eosinophilia, the degree of clinical symptoms or peripheral blood eosinophilia, and the degree of abnormalities on chest X-ray films should be extensively reevaluated. PMID- 1450494 TI - Selective IgM deficiency: functional assessment of peripheral blood lymphocytes in vitro. AB - The functional aspects of the peripheral blood lymphocytes from 6 patients with primary selective IgM deficiency (sIgMD) were analyzed to elucidate its pathogenesis. The surface IgM positive B cells were present at almost the same percentage as in controls, but the percentage of cluster of differentiation (CD)4+ T cells was higher and that of CD8+ T cells was low. The patient B cells showed a significantly lower proliferative response to Staphylococcus aureus Cowan strain I (SAC) than control B cells and did not produce a significant amount of IgM when co-cultured with control T cells. Interestingly, mitomycin C (MMC)-treated patient T cells induced a greater amount of IgM production by control B cells. In addition, patient B cells treated with SAC and B cell differentiation factors (BCDF) failed to secrete IgM. These results suggest that the pathogenesis of sIgMD may be mainly due to an intrinsic defect in B cell maturation. PMID- 1450495 TI - Ten-year follow-up of Japanese overweight subjects with impaired glucose tolerance: identification of a diabetes-prone subpopulation. AB - Ninety-four overweight subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) were followed for 10 years. No one from the NGT group developed diabetes, however 32% of the IGT subjects did develop diabetes. Initial data of the IGT subjects who developed diabetes were significantly different from those who did not develop diabetes. Fasting, peak and/or sigma plasma glucose (PG), IRI and CPR at 180 minutes and CPR/IRI at 0 and 180 minutes were increased, and the peak time of PG was delayed; also the prevalence of a positive family history was higher, and the body weight heavier. Seventy-nine percent of IGT subjects with the initial sigma PG of greater than or equal to 40 mM or a positive family history developed diabetes whereas only 3% of those with sigma PG of less than 40 mM and a negative family history developed diabetes. Therefore, it might be considered that among the overweight adults with IGT, those with sigma PG of greater than or equal to 40 mM or a positive family history are diabetes prone and those with sigma PG of less than 40 mM and a negative family history are diabetes resistant. PMID- 1450497 TI - Ataxic hemiparesis following thalamic lacunar infarction. AB - A 60-year-old man developed left hemiparesis and homolateral ataxia with normal sensation and normal somatosensory evoked potentials. A lacunar infarct with gadolinium enhancement in the right dorsolateral part of the thalamus was demonstrated on magnetic resonance imaging. Thalamic lesion is a relatively rare cause of ataxic hemiparesis; most of the reported cases of ataxic hemiparesis caused by thalamic lesion were accompanied by sensory disturbances. This is an interesting case which suggested that the thalamic lesion could be responsible for the ataxic hemiparesis without a sensory disturbance. PMID- 1450496 TI - The role of recombinant human tissue-type plasminogen activator in the treatment of acute pulmonary thromboembolism. AB - The effect of intravenous recombinant human tissue-type plasminogen activator (tPA) on arterial blood gases was compared with the effect of heparin treatment in acute pulmonary thromboembolism. Fifteen patients received heparin alone (group A), 5 cases were treated with 7.7 x 10(6) I.U. of tPA (group B) and 10 cases with 15 x 10(6) I.U. of tPA (group C) combined with heparin treatment. Arterial oxygen tension before treatment was not significantly different among the three groups. PaO2 was dramatically improved on the 1st day in group C. By the 7th day, PaO2 of group B had improved to the level of group C. However, the PaO2 of group A on the 7th day was not significantly different compared to the pre-treatment value. In group C, post-treatment perfusion lung scintigrams were improved compared to the pre-treatment images, but this was not the case in group B. Treatment with tPA is more effective for acute pulmonary thromboembolism than heparin alone and a high dose of tPA (15 x 10(6) I.U.) leads to rapid improvement in arterial blood gases and lung perfusion images. PMID- 1450498 TI - Periodic fever compatible with familial Mediterranean fever. AB - A 55-year-old male presented with a recurrent fever of over 38 degrees C, occurring at irregular intervals 1-6 times a month with chest, back or abdominal pain. After admission to our hospital, we found the following characteristics: 1) the febrile attacks were accompanied by obvious inflammatory findings and pleuritis or peritonitis; 2) the patient's elder sister had a similar periodic fever; and 3) there were no apparent causative factors responsible for his symptoms. Therefore, we diagnosed this as a case compatible with familial Mediterranean fever. The febrile attacks have been completely suppressed by daily colchicine. This is the seventh case of familial Mediterranean fever reported in Japan. PMID- 1450500 TI - Hyperparathyroidism associated with parkinsonism. AB - A 70-year-old woman with hyperparathyroidism associated with parkinsonism is reported. Her primary initial symptom was parkinsonism, but it was levodopa resistant. Chemical and hormonal findings revealed that she had hyperparathyroidism. The symptoms were relieved after the surgical removal of a parathyroid adenoma. Although this type of case has been reported only rarely, it suggests that hypercalcemia might be an aggravating factor in levodopa-resistant parkinsonism. PMID- 1450499 TI - Portal hepatic venous shunt via an intrahepatic portal vein aneurysm. AB - A rare case of portal hepatic venous shunt (PHVS) via an intrahepatic portal vein aneurysm (PVA) is presented. A 66-year-old man was admitted for examination of a mass in the liver. Ultrasonography demonstrated a cystic lesion (15 mm in diameter) at the posterior superior segment of the right hepatic lobe which communicated with the right portal vein (RPV) and right hepatic vein (RHV). Superior mesenteric portography showed a biloculate aneurysm in RPV and PHVS. Color doppler ultrasonography indicated that flow in the tracts entered the aneurysmal cavity from RPV and drained into RHV. PMID- 1450501 TI - Noonan syndrome presenting growth hormone neurosecretory dysfunction. AB - Noonan syndrome has been diagnosed by the characteristic physical stigmata for more than two decades. Recent studies of growth hormone secretory pattern provide a new category of growth hormone neurosecretory dysfunction to characterize short stature. We describe herein a case of growth hormone neurosecretory dysfunction in a 16-year-old boy with Noonan syndrome. Growth hormone neurosecretory dysfunction was diagnosed primarily based on the low amplitude and small numbers of the spontaneous bursts of growth hormone secretion during 12-hour nocturnal growth hormone sampling. Treatment with synthetic human growth hormone has markedly accelerated the growth velocity for one year and a half. This case notes the wide spectrum of short stature in Noonan syndrome and the effectiveness of treatment with human growth hormone. PMID- 1450502 TI - Klinefelter's syndrome accompanied by diabetes mellitus and diabetes insipidus. AB - The first case of Klinefelter's syndrome accompanied by diabetes insipidus and diabetes mellitus is reported. A 41-year-old man admitted for hyperosmolar diabetic coma with a past history of diabetes insipidus was diagnosed as having Klinefelter's syndrome by endocrinological examination and sex chromosome analysis. In this case, glucose tolerance test was normalized half a year later and blood glucose was well controlled with diet therapy alone. PMID- 1450503 TI - Quadriceps myositis. AB - A young woman with slowly progressive muscular weakness and atrophy localized in both thighs is reported. Laboratory, electromyographic and histological findings suggested that the patient suffered from chronic myositis with a background of autoimmune disorder. Quadriceps myositis is a rare condition. The previously reported cases of this disease in the literature are reviewed. PMID- 1450504 TI - Fatal pneumonia caused by Corynebacterium group JK after treatment of Staphylococcus aureus pneumonia. AB - A 76-year-old man who was admitted to the hospital because of chronic renal insufficiency and chronic hepatitis died of Corynebacterium group JK pneumonia, after showing a slight improvement by treatment of Staphylococcus aureus with sulbactam/cefoperazone and minocycline. Transtracheal aspiration (TTA) just before his death revealed numerous gram-positive bacilli phagocytized by many neutrophils and more than 10(8) colony forming units (CFU)/ml of Corynebacterium group JK. A drug susceptibility test showed Corynebacterium group JK was resistant to many antibiotics, with the exception of vancomycin and amikacin. PMID- 1450505 TI - Pseudomembranous bronchitis (non-diphtherial) resulting in sudden death: an autopsy report. AB - A 69-year-old woman was admitted because of dyspnea. Thereafter, she fell into a state of shock. Resuscitation was attempted but she did not respond to it and died on the second hospital day. According to the autopsy findings, a wide range of area from the larynx to the trachea was covered with pseudomembrane. In the culture of bacteria, alpha Streptococcus and Corynebacterium genus (non diphtherial) were all that was detected. These findings suggest that pseudomembranous lesion, an endogenous foreign matter of the air passage should be suspected when a patient presents with sudden dyspnea. PMID- 1450506 TI - Multiple myeloma complicated by congestive heart failure following first administration of recombinant alpha-interferon. AB - A 59-year-old female was admitted to Tsukuba University Hospital and diagnosed as IgA-lambda multiple myeloma (stage IIIA). No cardiovascular disorder with the exception of minor ischemic changes in ECG was revealed before treatment. Recombinant human alpha-interferon (IFN) at a dose of 3 million units combined with melphalan and prednisolone was administrated. Sixteen hours after the first administration of IFN, IFN was suspended by the symptoms of congestive heart failure (CHF). Treatment with diuretics and catecholamine products showed almost complete recovery from CHF in 3 weeks. An adverse reaction to IFN was strongly suspected as the cause of CHF. PMID- 1450507 TI - Inflammatory pseudotumor of the spleen. AB - The case of a 39-year-old man with inflammatory pseudotumor of the spleen is presented. This is an extremely rare benign lesion with histologic features of non-specific inflammatory and reparative changes. The literature is reviewed and this case is compared clinically and radiologically with the previously reported cases. PMID- 1450508 TI - Pulmonary intralobar sequestration accompanied by aneurysm of an anomalous arterial supply. AB - A 47-year-old woman presented with hemoptysis and her chest X-ray films showed an opacity suggesting a mass in the left lower lung field. Based on radiographic investigations, the mass was diagnosed as an aneurysm develop in an anomalous vessel and was considered to be a Pryce type I pulmonary intralobar sequestration. Resection of the left lower lobes was performed and the aneurysm was found to be filled with thrombus. It is rare for an aneurysm to form in an aberrant vessel. This complication may have been the result of regional sclerosis affecting the anomalous artery as well as systemic atherosclerosis. PMID- 1450509 TI - Rheumatoid nodules of the lung in a patient with palindromic rheumatism. AB - We report a case of rheumatoid nodules of the lung seen in a patient with palindromic rheumatism. A 54-year-old man with palindromic rheumatism was admitted for evaluation of three nodules in the right upper lobe on chest roentgenogram. Wedge resection was performed for the purpose of confirmative diagnosis and treatment. Histology of these lung lesions revealed palisaded histiocytic cells surrounding a layer of central necrosis, which were considered to be characteristic findings of rheumatoid nodule. Such a case is extremely rare. To our knowledge, only one other case has been reported before in the literature. PMID- 1450510 TI - Serum interleukin-2 receptor and interferon-alpha levels in a patient with allergic granulomatous angiitis (Churg-Strauss). AB - A patient with allergic granulomatous angiitis accompanied by increases in serum interleukin-2 receptor (IL-2R) and interferon-alpha (IFN-alpha) levels is reported. Laboratory findings revealed leukocytosis with eosinophilia and increased serum IgE and IgG. The serum IL-2R and IFN-alpha were increased. The serum immune complex, interferon-beta, -gamma and complements remained at normal levels. The serum IgE, IgG, IL-2R and IFN-alpha correlated with disease activity. Immunofluorescent studies using frozen sections obtained from the dermal lesion showed no immunoglobulin or complement deposits on vascular walls. Measurements of serum IL-2R and IFN-alpha might be considered reliable serologic indicators of disease activity. PMID- 1450511 TI - Hybridization fingerprinting of high-density cDNA-library arrays with cDNA pools derived from whole tissues. AB - As part of an integrated mapping and sequencing analysis of genomes, we have developed an approach allowing the characterization of large numbers of cDNA library clones with a minimal number of experiments. Three basic elements used in the analysis of cDNA libraries are responsible for the high efficiency of this new approach: (1) high-density library arrays allowing thousands of clones to be screened simultaneously; (2) hybridization fingerprinting techniques to identify clones abundantly expressed in specific tissues (by hybridizations with labeled tissue cDNA pools) and to avoid the repeated selection of identical clones and of clones containing noncoding inserts; and (3) a computerized system for the evaluation of hybridization data. To demonstrate the feasibility of this approach, we hybridized high-density cDNA library arrays of human fetal brain and embryonal Drosophila with radiolabeled cDNA pools derived from whole mouse tissues. Fingerprints of the library arrays were generated, localizing clones containing cDNA sequences from mRNAs expressed at middle to high abundance (> 0.1 0.15%) in the respective tissue. Partial sequencing data from a number of clones abundantly expressed in several tissues were generated to demonstrate the value of the approach, especially for the selection of cDNA clones for the analyses of genomes based on expressed sequence tagged sites. Data obtained by the technique described will ultimately be correlated with additional transcriptional and sequence information for the same library clones and with genomic mapping information in a relational database. PMID- 1450512 TI - Mouse microsatellites from a flow-sorted 4:6 Robertsonian chromosome. AB - Twenty microsatellites were generated from a previously characterized lambda gt10 library containing C57BL/6J mouse DNA from a flow-sorted 4:6 Robertsonian chromosome. These sequences were analyzed for size variation between different strains of mice with the polymerase chain reaction (PCR) and mapped by use of either strain distribution patterns (SDPs) in recombinant inbred (RI) strains, or intra- and interspecific backcrosses. Eighty-five percent of the sequences showed allelic variations between different inbred strains of mice and the wild mouse, Mus spretus, and 70% were variant between inbred strains. Eight (62%) of the 13 repeats that have been mapped lie on Chromosomes (Chr) 4 and 6. This approach is an effective way of generating informative markers on specific chromosomes. PMID- 1450513 TI - Mapping of the structural gene for S-adenosyl homocysteine hydrolase to mouse chromosome 2, and related sequences to chromosomes 8 and X. AB - Comparative mapping studies in human and mouse have shown that, to date, human Chromosome (Chr) 20 is completely syntenic with distal mouse Chr 2. The structural locus for S-adenosyl-L-homocysteine hydrolase (EC 3.3.1.1) in human, AHCY, maps to 20 qter-->q13.1, and we report here that the homologous locus in the mouse, Ahcy, maps to distal mouse Chr 2 with gene order Pcna-Ahcy-Ada. Analysis of 123 progeny of an interspecific backcross between a laboratory stock, AN, and Mus spretus using a rat cDNA probe revealed the presence of at least two other Ahcy-related sequences segregating independently in the mouse genome. One, Ahcy-rs1, was mapped to Chr 8 in the BXH recombinant inbred strains, and the other, Ahcy-rs2, shows a pattern of inheritance consistent with X-linkage. PMID- 1450514 TI - Genomic mapping by single copy landmark detection: a predictive model with a discrete mathematical approach. AB - One of the goals of the Human Genome Project is to produce libraries of largely contiguous, ordered sets of molecular clones for use in sequencing and gene mapping projects. This is planned to be done for human and many model organisms. Theory and practice have shown that long-range contiguity and the degree to which the entire genome is covered by ordered clones can be affected by many biological variables. Many laboratories are currently experimenting with different experimental strategies and theoretical models to help plan strategies for accomplishing long-range molecular mapping of genomes. Here we describe a new mathematical model and formulas for helping to plan genome mapping projects, using various single-copy landmark (SCL) detection, or "anchoring", strategies. We derive formulas that allow us to examine the effects of interactions among the following variables: average insert size of the cloning vector, average size of SCL, the number of SCL, and the redundancy in coverage of the clone library. We also examine and compare three different ways in which anchoring can be implemented: (1) anchors are selected independently of the library to be ordered (random anchoring); (2) anchors are made from end probes from both ends of clones in the library to be ordered (nonrandom anchoring); and (3) anchors are made from one end or the other, randomly, from clones in the library to be ordered (nonrandom anchoring). Our results show that, for biologically realistic conditions, nonrandom anchoring is always more effective than random anchoring for contig building, and there is little to be gained from making SCL from both ends of clones vs. only one end of clones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450515 TI - Mapping of two human homologs of a Drosophila heterochromatin protein gene to the X chromosome. PMID- 1450516 TI - Linkage among esterase-6 (Es-6), neural cell adhesion molecule (NCAM), and apolipoprotein C-III (apoc-3) genes on rat chromosome 8. PMID- 1450517 TI - The gene coding for the immunoglobulin heavy chain binding protein BiP (Hsce-70) maps to mouse chromosome 2. PMID- 1450518 TI - Factors in biological fluids affect gel filtration behavior of epidermal growth factor. AB - There have been conflicting reports on the presence of multiple forms of epidermal growth factor (EGF) in human saliva. The present study was initiated to study the gel filtration behavior of EGF in saliva and other biological fluids. In addition, studies were performed to determine if there were factors in saliva or other biological fluids that would influence the gel filtration behavior of EGF. Gel filtration studies with saliva and urine demonstrated EGF migration consistent with a molecular weight of 35 kDa with no heterogeneity observed. The addition of radiolabeled EGF to either saliva or urine resulted in an altered migration on gel filtration. These results provide evidence for a protein-peptide interaction in saliva and other biological fluids that alters the apparent physical properties of mature EGF. PMID- 1450519 TI - Suppression of interleukin-1 action by phospholipase-A2 inhibitors in helper T lymphocytes. AB - The mechanism by which interleukin 1 (IL-1) and T cell receptor (TCR) activation co-stimulate T helper (Th) cells is not clear. In chondrocytes, fibroblasts and several other cell types, much of the evidence suggests a linkage between IL-1 action and increased phospholipase-A2 (PLA2) activity. Although Th cells have very low levels of PLA2, they are well known targets for IL-1. We studied the effects of PLA2 inhibitors, i.e., lipocortin-1 (LC-1) and the synthetic peptide antiflammin-P2 (AF-2), on the enhancing effect of IL-1 upon activation of TCR. When murine D10.G4.1 Th2 cells were stimulated by their clonotypic anti-TCR antibody 3D3, both LC-1 and AF-2 inhibited the biological response to IL-1. This blockade was not seen when D10 cells were induced to proliferate with interleukin 2 (IL-2) and 3D3 in the presence of the same inhibitors, LC-1 or AF-2. These results strongly suggest that PLA2 also plays a central role in mediating the actions of IL-1 in the helper T cell. PMID- 1450520 TI - Compatibility of the S-(3-nitro-2-pyridinesulfenyl) protecting group with DCC/HOBt coupling chemistry. AB - Two recent reports on the partial lability of the 3-nitro-2-pyridinesulfenyl (Npys) thiol protecting group towards 1-hydroxy-benzotriazole (HOBt) have prompted a rechecking of the chemical behavior of this group. Using both soluble and polymer-bound forms of Cys(Npys) as test materials, the complete stability of this protection against HOBt has now been definitively established, and its compatibility with Boc-benzyl-based solid-phase synthesis strategies has been clearly confirmed by stability assays against a wide range of reagents, as well as by the successful synthesis of several Cys(Npys)-containing peptides. PMID- 1450521 TI - Solution synthesis of calciseptine, an L-type specific calcium channel blocker. AB - Calciseptine, an L-type specific calcium channel blocker consisting of 60 amino acid residues with four intramolecular disulfide bonds, was synthesized by the solution procedure applying our maximum protection strategy. The recently developed solvent systems used were a mixture of chloroform or dichloromethane and trifluoroethanol; they were useful for the synthesis of slightly soluble protected peptides. After removal of all the protecting groups by our two-step HF procedure followed by treatment with mercuric acetate, the peptide was folded into its native form by air oxidation, in which redox reagents were necessary to accelerate the correct disulfide bond formation. The product was purified to homogeneity and found to block contractions of the rat thoracic aorta induced by 40 mM K+ with the same potency as that of the natural product. In addition, this peptide was found to block contractions of various rat smooth muscle preparations as well as increase in cytosolic free calcium concentration induced by a high concentration of extracellular K+. PMID- 1450522 TI - Preference of human cdc2 kinase for peptide substrate. AB - Human cyclin B1-bound cdc2 kinase phosphorylated the threonine residue in the sequence -Thr-Pro-Lys-Lys-Ala- but hardly phosphorylated it in the sequence -Thr Pro-Lys-Ala-Lys. The sequence -Thr-Pro-Ala-Pro-Lys-, as found in p53 protein, was also phosphorylated by this enzyme, but less efficiently than in the sequence described above. When the threonine residue in -Thr-Pro-Lys-Lys-Ala- was changed to a serine or a tyrosine residue, the enzyme phosphorylated the serine, but not the tyrosine residue. Changing the lysine next to the proline to alanine reduced its efficiency as a substrate. The peptide, Ala-Ala-Ala-Ala-Lys-Thr-Pro-Ala-Lys Ala-Ala, containing the -Thr-Pro-Ala-Lys- sequence, but not the other lysine residues, was not used as a substrate by the kinase. PMID- 1450523 TI - N alpha-trifluoroacetylation of N-terminal hydroxyamino acids: a new side reaction in peptide synthesis. AB - In the synthesis of the double-chain bis-cystinyl hinge fragment 225-232/225' 232' of the human IgG1, which contains two N-terminal threonine residues, the final acidolytic deprotection step, with 99% aqueous trifluoroacetic acid, was accompanied by formation of remarkable amounts of an unknown side product. This has been identified as the N alpha-mono-trifluoroacetylated product; however, even bis-trifluoroacetylation was found to occur by prolonged exposure of the parallel dimer to the reaction medium. Similarly, the model compounds H-Thr(tBu) Phe-OH, [Boc-Thr(tBu)-Cys-OH]2 and Boc-Thr(tBu)-Cys(StBu)-Ala-OH were acylated by treatment with trifluoroacetic acid at rates that suggest a rather pronounced sequence dependency. Since, on the other hand, the model compound [Boc-Ala-Cys OH]2 was not trifluoroacetylated at all under identical conditions, the reaction has to proceed prevalently via intermediate formation of the trifluoroacetyl ester of N-terminal hydroxyamino acids, followed by O-->N shift according to the hydroxyoxazolidine mechanism. The experimental data indicate also that under favored conditions aminolysis of the trifluoroacetyl ester via an inter- or intramolecular pathway may contribute to the overall reaction rate. PMID- 1450524 TI - Use of 6 M HCl for removal of the N-alpha-tert-butyloxycarbonyl group during solid-phase peptide synthesis. AB - We describe the use of 6 M HCl to remove the Boc group in solid-phase peptide synthesis. Three peptides, 4-10 amino acid residues in length, have been successfully synthesized using 6 M HCl and were found to be comparable in purity to the same peptides prepared using the standard 50% trifluoroacetic acid in dichloromethane method of N-alpha-Boc removal. PMID- 1450525 TI - Copper (II) complexes as a laccase model in the catalytic removal of the phenylhydrazide protecting group under mild oxidative conditions. AB - Copper (II) complexes, with nitrogen-containing ligands (pyridine and imidazole), simulate perfectly the catalytic activity of laccase in the oxidative removal of the phenylhydrazide protecting group. Deblocking occurs under mild conditions, preventing the oxidation of labile amino acids. The effect of certain factors on the rate of deblocking and the degree of conversion were studied, and optimal conditions providing 100% yield of the deblocked products were chosen. PMID- 1450526 TI - [Laudatio with reference to presenting the Johann-Peter-Frank Medal 1992]. PMID- 1450527 TI - [The environment and ethics]. PMID- 1450528 TI - [Approach to current topics in public health]. PMID- 1450529 TI - [Education and continued education in public health. Wishes and reality at the present time; demands for the future]. AB - Sociomedicine in research and practice, i.e. in universities and in public health services, has experienced an upswing many had not expected. The health requirements of society and not only those of the individual have gained a new topicality as social factors were rediscovered in connection with health. Public health services can be advisors to politicians and defence attorneys for the population by assuming a new role and a new measure of self-understanding in the realisation of old but always fresh topics such as environmental medicine (formerly known as environmental hygiene). To translate the multitude of sociomedical tasks effectively into reality, the practically active sociomedical officer in public health services stands in need of the backing and help by sociomedical researchers in the relevant university departments. It will be imperative to achieve in future a greatly improved and closer cooperation between research and practice in sociomedicine. PMID- 1450530 TI - [Educational emphasis at university centers]. AB - In Germany four postgraduate courses in public health were set up since 1989. They all offer a public health training including research activities, field experience and international perspectives. The public health administration should decide in the near future whether this new training could be passed by the public health officers instead of the compulsory courses in the academies in Dusseldorf and Munchen. PMID- 1450531 TI - [Quality assurance: introduction and legal principles]. AB - Quality assurance has been part of clinical medicine and public health for decades, but only recently have structured and well documented procedures of quality assurance been introduced. Industry has been a model. Since 1. 1. 1989 quality assurance in Germany has been a legal requirement for a wide range of health services. Structure, process and outcome as part of quality assurance is defined as well as criteria, standards and norms. The development of quality assurance in Germany is described. The importance of quality assurance for the efficacy, efficiency and the aim-orientated work of the public health services and for the medical service of the compulsory health insurance is stressed. PMID- 1450532 TI - [Quality assurance in the public health office]. AB - Quality is assured not only by long-standing experience; it must be continually safeguarded. Preconditions are as follows: qualified training with scientific background and continual scientific supervision; regular continuing education via exchange of experience; standardising of methods on a intra-office level and by inter-office exchange on Lander level; internal and external cooperation; validity and plausibility controls; interdisciplinary cooperation. These principles are discussed by means of examples of health protection--health protection on environmental protection principles--expertising--medical statistics/health planning--health care aid/health advisory service. PMID- 1450533 TI - [Health promotion by the public health service (with special reference to promoting the self help movement)]. AB - During the last decade there has been a new orientation in public health policies. The question of prevention is gaining importance and has assumed social and political dimensions alongside the traditional medical issues. In future the public health service will increasingly recognise the value of an interdisciplinary approach, as was emphasised in a Resolution by the 64th German State Health Ministers' Conference. The need for cooperation and coordination in important future fields of action--especially the area of Self-Help--is presented as a major challenge for the Public Health Department. Details are given on the new requirements in terms of organisation, staffing and facilities. PMID- 1450534 TI - [High immunization rates--how can they be achieved at all?]. AB - High rates of immunization are achieved not only by compulsory vaccination. Strict discipline is necessary as well as motivation of medical assistants and of patients in their social environment. All people have a natural instinct for protecting themselves against risks of life. This instinct can in fact be stimulated by repeated motivation and can be enforced by propaganda. The process of propaganda alone cannot stimulate urges. Strategy of immunization must be standardised in all districts of the Federal Republic. This means: immunisation schedule, information of patients, children and of their parents. This is part of discipline of vaccination, same as is the permanent training of medical staff. They should be sent to seminars and training workshops. Specialist opinions must be differentiated as to whether they are scientists or articulate their own and personal opinion or whether their attitude is conditioned by general medical considerations. Any legal claims arising from vaccination accidents would be decided 'in dubio pro aegroto'. PMID- 1450535 TI - [Vaccination against Haemophilus influenzae B and rubella]. AB - Haemophilus influenzae B was the most frequent pathogen of bacterial meningitis in childhood during the mid-eighties to the end of the eighties of the present century, taking the place of meningococci since approximately 1984 at about twice the rate of that pathogen, as shown by the records kept during 1980-1990 in Bavarian Departments of Paediatrics. In fact, in 1990 the incidence of HIB meningitides was about 2.5 times that of meningococcus meningitides (85 vs. 34, respectively). For practically 2 years now vaccination against HIB is being publicly recommended and should be made use of as intensively as possible to prevent all HIB infections. For several years the principle of on-target rubella vaccination has been applied to schoolgirls in Lower Saxony, Bremen and Hamburg to prevent rubella embryopathy, a procedure that has proved much more successful than blank vaccination. None of the other Federal German Laender have been following this procedure to date; in consequence there of, although the strategy of on-target vaccination will be continued in Lower Saxony, greater uniformity and greater efficiency are being aimed at throughout Germany by public recommendation of rubella vaccination at an infant age. PMID- 1450536 TI - [Between isolation and acceptance--hepatitis B and AIDS in community facilities]. AB - Both Hepatitis B and the HIV-infection are spread either through blood or sexual contact. The danger of these infections spreading in day nurseries and schools is very remote but nonetheless there are confused fears. These fears lead to isolation and enormous problems for the carriers, who, for the most part, are children but can also be adults. As far as Hepatitis B, HIV and AIDS are concerned there are clear scientific recommendations for those attending these social institutions. Such recommendations have been published in decrees by the responsible ministries of the Lander of the Federal Republic of Germany. These decrees enable infected children and adolescents to lead an accepted life within the community. They reduce the remaining extremely small risk of transmitting the diseases to a level that is in fact lower than the general risk of every-day life and can be tolerated in an empathic society. PMID- 1450537 TI - [The epidemiology of whooping cough]. AB - Due to a low acceptance of active immunisation against Bordetella pertussis, whooping cough continues to be a frequent childhood disease in parts of Germany. The age distribution in the lower Rhine area showed a peak incidence at 4.3 years of age, whereas 11% of all cases were observed in infants, and 6% were observed in adults. A significant sex difference was not found in children suffering from pertussis; in adult patients, however, women were more often affected. Whooping cough occurred during the whole year, its peak incidence was found during early winter. In children, paroxysmal coughing fits, vomiting and whooping were the primary symptoms of disease; adults and infants, however, developed these symptoms only in reduced frequency. About 25% of all cases showed an atypical course, and could only be diagnosed by laboratory tests. While leukocyte count and ESR did not have diagnostic significance, a combination of microbiological and serological tests showed a high diagnostic sensitivity and specificity. In contrast to the former GDR and to most European neighbours, the former Federal Republic overrated the side effects of active vaccination as compared to the various risks of natural infection. This resulted in a decline of vaccine acceptance to less than 10% in several areas of the former FRG. It is anticipated that the altered recommendation in favour of vaccination, and especially the future application of acellular vaccines with less side effects, will result in the elimination of whooping cough in all areas of Germany. PMID- 1450538 TI - [Early special education and integration from the viewpoint of a social pediatric center]. PMID- 1450539 TI - [Rehabilitation of handicapped children as the combined responsibility of medicine and pedagogics--approach and contradictions in the process of integrated education]. AB - The development of common education of handicapped and non-disabled children in kindergartens and schools has removed all doubt that disabled children are encouraged and helped to a considerable degree whereas non-disabled children acquire more social aptitude. In no case need one fear that their learning performance is negatively affected by integrated education. This is of course conditional on the availability of suitable conditions under which such integrated education takes place. The medical profession as a whole did not participate in the development and testing of integrative models and test projects. The main reasons for this are difficulties in communication between physicians and educationists, which require to be discussed. The article describes the need for cooperation by physicians in further development of integrative measures, their possibilities of influencing the development, and their special task in cooperating with educational experts, from a paedogical aspects; finally, the sociopolitical and medicopolitical tasks of the medical profession in Public Health services are pointed out. PMID- 1450540 TI - [Responsibilities of pediatric medicine in integrated rehabilitation of handicapped children in Bremen]. AB - Integrated education of handicapped children in Bremen is both goal and method. In the case of infants (0-3 years old) integration means integrating the child into the family by working with and within the family; for pre-school children (3 6 years old) this means education with non-handicapped children in a pre-school setting; integration in school settings using various approaches is still a goal. Integrated education is understood as a multi-disciplinary approach with the necessary inclusion of sociopaediatric competencies. The contribution to the concept of integration by paediatricians in Bremen is presented in this article. The work described is viewed as a perfect fit for paediatricians in the Public Health Services if they have the necessary preliminaries in self-understanding and qualification. PMID- 1450541 TI - [Psychological testing within the scope of social psychiatric service]. AB - As a psychologist working within the Social Psychiatric Service I find myself exposed to certain assignments and methodological expectations. One of the most common images is that of a "trick- and test specialist" that most of the time would appear along with multitude of open and hidden fantasies towards psychological methods of testing. It's not always easy to meet such expectations appropriately. But due to the severe consequences that may arise from statements of the Service we have to emphasise the limitations of such means of assistance. The mathematical operations of test constructors may be extraordinarily brilliant; the possibilities of transforming psychic phenomena into abstract numbers create however, as many complications as the choice of social scales and standards we have to make for our measurements. Hence, psychological results will still have to follow several different steps of examination that are reciprocally related to each other, even when using methods that seem to provide more comfortable, easier solutions. PMID- 1450542 TI - [Prostitution--a sequela of sexual abuse]. AB - AIDS has consolidated the isolated state of prostitutes and stigmatized them as HIV carriers. Due to the threat of AIDS, the Berlin senate has worked out a programme for prostitutes. For the programme to succeed, knowledge of the causes of prostitution is a prerequisite, such as sexual abuse during childhood and adolescence. The sexually abused who have gone without psychological help are prone to prostitution. The work and its evaluation by a psychologist is presented to help counselling Services on Venereal Diseases in their work. PMID- 1450543 TI - [AIDS counseling in social welfare for prostitutes in the rural area]. AB - Prostitute welfare and AIDS counselling are in the hands of one person in the rural area of the Westerland district. This offers the opportunity of continuously preventing this disease and giving guidance and the "human touch" in close care in case of a possible infection, especially in view of the lower number of cases examined and advised compared with the figures in the big cities. An anonymous poll among 41 prostitutes shows that they approve of and are satisfied with the concept of the "G-welfare". It also shows that the prostitutes themselves are hardly aware of the HIV-risk, that their customers only rarely accept condoms and that there are problems in the use and the toleration of condoms. These difficulties are the main aspects of the preventive work, as well as the psycho-social care and the personal relationship to those examining. PMID- 1450544 TI - [Results from the Frankfurt a.M. AIDS counseling unit 1988 and 1989]. AB - An AIDS counselling office of the Public Health Service has been available to the public of Frankfurt a.M. since September 1985. 6969 blood samples were examined for HIV antibodies between January 1988 and the end of December 1989. The prevalence of positive tests was 1.9% (n = 141). Until now most of the HIV positive clients are homo- and bisexual persons. Security and partnership were the most frequent reasons stated by heterosexual clients at the AIDS-counselling office. PMID- 1450545 TI - [Yes to sex education, but comprehensive, please. The health fair medium in health promotion, 6 years experiences exemplified by AIDS education]. AB - The basic conditions for HIV/AIDS prevention have been changing during the last years. The interdisciplinary approach must be emphasised very clearly nowadays. Models of cooperation within the community must be enhanced. AIDS counselling in Bremen underwent various stages: from a critical analysis of the risk factor theory to the life-style concept and to a call for community action. The paper points out how the 6 years of experience with a special AIDS exhibition can be utilised for health education in other fields. PMID- 1450546 TI - [Special characteristics of physician involvement in AIDS counseling]. AB - Characteristic features of medical work at an AIDS Information Centre are pointed out with particular regard to the present situation in the city and district of Crenter? Hannover. Persons infected with HIV are reviewed, drawing particular attention to the extreme stress of living with the knowledge of being HIV infected. The arising social problems of HIV-positive patients are described together with the doctor's adviser of easing the patient's stress and guiding him into accepting the necessary changes in life. Intensive cooperation hospital doctors, GP's and social workers is described. PMID- 1450547 TI - [Medical management of HIV infected and AIDS patients in the Hannover metropolitan area as an interdisciplinary construct]. AB - Two wards for consultation of AIDS have opened in Hannover in 1987, one in the Public Health Department for the city of Hannover, the other in the Public Health Department for the surroundings. It was a big step towards prevention of AIDS. At the same time a centre, especially for AIDS, was opened at the Medical college of Hannover, consisting of an ambulance and beds in a ward. An official laboratory tests the medical analyses. Today the doctor in the Public Health Department plays an important part: he is the first partner with whom the infected patient can talk. He must also maintain contact with all institutions including the family doctor for optimum patient care. PMID- 1450548 TI - [Effect of air pollutants on the organism of the child]. AB - The Institute of Hygiene at Rostock initiated studies in 1980 on schoolchildren (1st to 4th form) in air-hygienically differently affected areas of the former GDR, as well as studies on probationers of the same age in non-polluted areas. The spectrum of methods included besides clinical, sensorial and psycho diagnostical investigations, also haematological, immunological and pulmonary functions tests. The results indicate that the state of health of children living in industrial areas is impaired. After a recuperating for four weeks under clean air conditions the changed values were normalised and adapted to the values of the non-exposed control group. The long-term effect of the recuperating stay lasts for 9 months. PMID- 1450549 TI - [Incidence of leukemia in the Elbmarsch area]. AB - The extremely conspicuous excess of leukaemia in the immediate neighbourhood of the world's largest boiling water reactor Krummel is shown in its temporal and spatial context. An early extensive Lower Saxony state research programme gives no hint what so ever for a cause beyond three known risks of the region: 1. the main point is that the radiation exposure is well-known for causing leukaemia; 2. contamination of drinking water with an unknown substance containing nitrogen; 3. emissions from a chemical factory (according to a brief toxicological report, however, without potential for causing leukaemia). The leukaemia cluster is discussed against the background of a new valuation of radiation risk derived from recent Hiroshima data and the Mainz Leukaemia Study published in February, which points out in analogy to late British studies a significant increase in the leukaemia risk for the most radiation-sensitive group of infants and young children (aged 0-4) in the proximity of nuclear power plants. PMID- 1450550 TI - [Legionella contamination in warm water systems of a large German city]. AB - Since 1988 the Frankfurt City Health Department examined the hot water systems of all public indoor swimming pools, old age homes and hospitals, and made subsequent checks on the corrective measures introduced. In the 6 public indoor swimming pools the percentage of positive legionella findings, after corrective measures has dropped since 1988: at the central hot-water supply units from 47% to 23%, and at the peripheral tap connections from 66% to 22%. The number of negative samples rose from 43% to 77%. Thus the favourable effect of the corrective measures is demonstrated. Since 1988 samples have been taken from the shower water at old age homes. An increase in negative findings could be shown (from 58% to 70%). From 1990, however, an increase of high-level legionella contamination (> 10,000 Legionella colonies per litre) was detected as well. In one home with a generally high legionella contamination level (up to 75,000 legionella colonies per litre) an investigation of the legionella antibodies was done in the blood of 44 residents whose medical history included fever or bronchial symptoms. In no case a previous infection could be demonstrated. However, there was one patient with a definite legionella pneumonia in the home: this patient usually had been showering for at least 20 minutes a day. Legionella were found in the hot water systems of 16 of the 17 hospitals in Frankfurt. In 1991 more than half to the 204 samples were legionella positive. 5% of the samples had legionella contamination levels of more than 100,000 per litre. Corrective measures have been taken.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450551 TI - [Ethical judgments in environmental medicine]. AB - Among the main tasks of environmental medicine within the framework of the German Public Health Service are the assessment and management of risks involved in environmental problems. The article points out that both tasks involve ethical judgments in crucial matters. An important part of risk management is to establish limit and guiding values. The examples of drinking water regulations and WHO Air Quality Guidelines show that these values depend mainly on decisions on standard settings. It is pointed out that these cannot be derived from knowledge gained from research in natural science and that our present heterogeneous civilization is not conductive to a generally recognised basis for an evaluation. It is suggested to solve this dilemma by a process of mutual agreement on a reciprocal basis. The models of "proxy consent" and "presumed intent" are discussed. Public Health Service must therefore systematically reflect, expose and develop the standard settings of its judgments and actions. PMID- 1450552 TI - [Regional service for senior citizens--a responsibility of the public health office]. AB - At present the share of persons over 60 years of age in the total population is about 20 per cent. The number of persons of very advanced age and of persons in need of permanent care is increasing. Planning care of such persons is one of the major problems of society in the coming decades. This means that Public Health offices will have to tackle important problems in planning, in an advisory capacity and in expertising. The article describes the activities of the "Planning Group Concerned with Care for Persons of Advanced Age" under the supervision of the Public Health Office in Schleswig-Holstein district. PMID- 1450553 TI - [Assistance for the aged from the viewpoint of the public health office]. AB - Problems of old age and ways of helping the old were discussed with various social and age groups, among them secondary pupils as well as people living in old people's homes. The main questions which arose were: "How can one give a purpose to one's old age?"--"How does one win sufficient recognition?"--"What can be done to avoid, or overcome, isolation?" Most senior citizens were in favour of spending their old age in their familiar surroundings--either on their own or with their families, in whose life they wanted to participate. Our inquiries have shown that there are more institutions than generally assumed which offer advice and help and can be consulted by those in particular who have decided against living in an old people's home. With the support of other institutions and authorities, the staff of the local Health Service drew up a brochure on "Assistance in Old Age", which covers the Kulmbach area. Then we tried to find ways of improving the quality of our senior citizens' lives without spending too much money. The key issue which emerged was prevention. PMID- 1450554 TI - [Social medicine aspects in expert assessment according to the new long-term care legislation]. AB - According to the new German 'Betreuungsgesetz' (BtG) legislation concerning care for the mentally and or physically disabled, instituting a "case of care" requires an expert opinion on the patient's mental and physical impairments as well as on the question as to what degree the patient lacks the ability to manage his or her own affairs. The respect for the personal autonomy has to be weighed against the need to take action for the patient's benefit. The concept of 'neglect' ('Verwahrlosung') plays an important role in judging a patient's situation. Criteria for the use of this term are derived from a study carried out by the author, and lead to a questionnaire designed for preparatory investigations. As to the question of who should act as an expert in BtG cases, the author argues that the public health offices qualify best for this task. PMID- 1450555 TI - [Expert assessment for long-term care--starting point for comprehensive help in medical and social rehabilitation]. AB - Based on the various definitions of people in need of constant care the authors describe the needs and chances of professional assessment in the process of financing care at home and in nursing homes. They stress the often neglected point of rehabilitation and plead for participation of social workers and nurses in the assessment process. The precarious situation for many relatives of people in need of care is pointed out. The authors come to the conclusion that public health offices in Germany should--as an important task in the future--concentrate more intensively on the actual problems of people in need of care and participate in local strategies to improve their living conditions. PMID- 1450556 TI - Effectiveness of a bioremediation product in degrading the oil spilled in the 1991 Arabian Gulf War. PMID- 1450557 TI - Degradation of selected insecticides by bacteria isolated from soil. PMID- 1450558 TI - Levels of polychlorinated biphenyls, organochlorine pesticides, and chlorophenols in the Kupa River water and in drinking waters from different areas in Croatia. PMID- 1450559 TI - Sources of pollution at Mina al Fahal coastal area. PMID- 1450560 TI - Characterization of monochlorinated biphenyl products formed by Paul's Scarlet Rose cells. PMID- 1450561 TI - Determination of N-nitrosodimethylamine in thiram formulations using steam distillation followed by solid phase extraction/enrichment. PMID- 1450562 TI - Photochemical degradation of pesticides: photocatalytic effect of Fe(III) ions on methylene blue sensitized interaction of 4-chlorophenoxyacetic acid with H2O2. PMID- 1450563 TI - Distribution and metabolism of 2,5,2'-trichlorobiphenyl in houseflies (Musca domestica L.). PMID- 1450564 TI - Effect of long-term uptake of mercuric sulphide on thyroid hormones and glutathione in mice. PMID- 1450565 TI - Alterations in biochemical composition of skeletal muscle during aflatoxicosis in rabbits. PMID- 1450566 TI - Alterations in erythrocytes during induced chronic aflatoxicosis in rabbits. PMID- 1450567 TI - Induction of micronuclei in mice bone marrow cells by home made aguardientes collected in southern Chile and their incidence in gastric cancer. PMID- 1450568 TI - Cutaneous toxicity of sodium lauryl sulphate, nickel, and their combination in guinea pigs: biochemical and histopathological observations. PMID- 1450569 TI - Use of 4-(nitrobenzyl)pyridine (4-NBP) to test mutagenic potential of slow reacting epoxides, their corresponding olefins, and other alkylating agents. PMID- 1450570 TI - Toxicity of acrylonitrile in a human neuroblastoma cell line and its effect on glutathione and glutathione-S-transferase. PMID- 1450571 TI - Chemosensory and electrophysiological responses in toxicity assessment: investigations with a ciliated protozoan. PMID- 1450572 TI - Acute toxicity of cadmium, copper, mercury, and zinc to ciliates from activated sludge plants. PMID- 1450573 TI - Influence of rain and sulphur dioxide on low level chemiluminescence from leaf of Populus tomentosa. PMID- 1450574 TI - Effects of different dilution water types on the acute toxicity to juvenile Pacific salmon and rainbow trout of fluroxypyr formulated product XRM-5084. PMID- 1450575 TI - Effects of contaminants of macrobenthic communities in the upper Calcasieu Estuary, Louisiana. PMID- 1450576 TI - Parathion and salinity effects on gills and mesonephros carbonic anhydrase activity of the fish Oreochromis hornorum. PMID- 1450577 TI - Free radical theory of aging: history. AB - Aging is the accumulation of changes responsible for the sequential alterations that accompany advancing age and the associated progressive increases in the chance of disease and death. These changes can be attributed to disease, environment, and the inborn aging process. The aging process is now the major risk factor for disease and death after about age 28. The free radical theory of aging arose in 1954 from a consideration of aging phenomenon from the premise that a single common process, modifiable by genetic and environmental factors, was responsible for the aging and death of all living things. The theory postulates that aging is caused by free radical reactions, i.e., these reactions may be involved in production of the aging changes associated with the environment, disease and the intrinsic aging process. The origination of the theory and its application to the problem of increasing the functional life span are discussed. Support for the free radical theory of aging has increased progressively and now includes: 1) studies on the origin of life and evolution, 2) studies on the effect of ionizing radiation on living things, 3) dietary manipulations of endogenous free radical reactions, 4) the plausible explanations it provides for aging phenomena, and 5) the growing numbers of studies that implicate free radical reactions in the pathogenesis of specific diseases. The rapidly growing number of scientists involved in studies on the role of free radical reactions in biological systems should assure future significant increases in the healthy, useful, life span of man. PMID- 1450578 TI - Relationship between antioxidants, lipid peroxidation and aging. AB - Experiments performed on species as different as flies, rats and frogs are not conclusive about the possibility that antioxidant defenses decrease in old animals. Even when these decreases are found, their physiological meaning is far from clear. Furthermore, a constancy of antioxidant capacity in old age is consistent with the fact that aging is a progressive phenomenon which occurs at a rather constant rate from the mature young to the very old animal, without showing a great acceleration rate in the aged. Nevertheless, experimental results strongly suggest that the maintenance of an appropriate antioxidant/prooxidant balance does have an important role in maintaining health in the aging animal. It is possible that the continuous presence of small amounts of free radicals in the adult tissues of both mature adults and old animals is an important factor in aging (a progressive phenomenon) and susceptibility to disease. Since, similarly to what occurs in procariota, the whole antioxidant system seems to be under homeostatic control in vertebrates, it is imperative to perform comprehensive and detailed studies on the effects of carefully controlled doses of antioxidants on biomarkers of health as well as on the different endogenous cellular antioxidant and prooxidant systems. These studies should have as a final goal the knowledge of which doses of antioxidants are high enough to increase antioxidant protection but low enough to avoid feedback depression of other endogenous antioxidants; this could further improve the health state of humans situated in the middle and last phases of their life span. PMID- 1450579 TI - Free radical theory of aging: view against the reliability theory. AB - The reliability theory approach to the free radical theory of aging is presented. First, the structural and functional inhomogeneity - hierarchy - of living systems has been taken into account. Hence, the existence of the finite number of critical structures - supervisors - in the system has been postulated. Second, I have postulated the stochastic nature of age-changes in the supervisors, paying particular attention to oxygen free radicals as the by-products of normal oxidative metabolism. Third, according to the cooperativity of main processes in biological systems, the existence of the threshold values of the reliability parameters of the supervisors has been postulated. In the terms of this reliability free radical theory of aging it becomes possible to explain the character of age-changes in mortality data for humans and animals; to explain how the linear kinetics of accumulation of free radical damages in the cellular targets (supervisors) can lead to the exponential kinetics of the mortality rate growth with age, i.e., to deduce the so-called Gompertz law of mortality; to explain the nature of the well-known empiric interspecies correlations between the maximum life span values and metabolic factors; to estimate species-specific life span potentials of humans and animals. The chromosomes of neural postmytotic cells have been suggested to function as the supervisors. In the terms of the theory it has been estimated that the life span of primates could run up 250 years but for the damages due to the oxygen free radicals. PMID- 1450580 TI - The metabolism of 4-hydroxynonenal, a lipid peroxidation product, is dependent on tumor age in Ehrlich mouse ascites cells. AB - 4-Hydroxynonenal is a major product formed by lipid peroxidation from omega 6 polyunsaturated fatty acids as linoleic acid and arachidonic acid. This aldehyde is cytotoxic at high concentrations (in the range of 100 microM), disturbs cell proliferation at low concentrations and exhibits genotoxic effects. Furthermore, in the submicromolar range 4-hydroxynonenal is chemotactic and stimulates phospholipase C. 4-Hydroxynonenal is rapidly metabolized in eucaryotic cells. Here the metabolism of 4-hydroxynonenal was studied in suspensions of Ehrlich mouse ascites cells at different periods of the tumor age. The Ehrlich ascites tumor is a convenient biological model for the investigation of tumor cells in different age and proliferation phases of the tumor. The main products of 4 hydroxynonenal which were identified in the Ehrlich ascites cells were glutathione-HNE-conjugate, hydroxynonenoic acid and 1,4-dihydroxynonene. The formation of glutathione conjugates following the addition of 4-hydroxynonenal was higher in cells of the early phase in comparison with cells of the late phase of tumor growth. That was in accordance with the increased consumption of the reduced form of glutathione during 4-hydroxynonenal utilization. The degradation of 4-hydroxynonenal and other aldehydic products of lipid peroxidation is postulated to be an important part of the intracellular antioxidative defense system. PMID- 1450581 TI - Effect of aging on glutathione metabolism. Protection by antioxidants. AB - The free radical theory of aging suggests that oxygen free radicals may be involved in the aging process. Thus, changes in antioxidant mechanisms may occur with aging. Since glutathione is one of the most effective antioxidant systems in the cell, its metabolism may change with aging. In this chapter we describe experiments which show the involvement of glutathione in the aging process and which provide a rationale for the administration of antioxidants to old organisms to protect them against some of the changes that occur with aging. PMID- 1450582 TI - Inhibition of LDL oxidation by antioxidants. AB - Low density lipoprotein (LDL) consists of about 3000 fatty acids (50% polyunsaturated) and a single molecule apolipoprotein B (500 kDa). The endogenous antioxidants of LDL consist mainly of tocopherols and few carotenoids, which protect the PUFAS against oxidation. That native LDL contains traces of oxidation products has not been proved yet. Oxidatively modified LDL (oLDL) exhibits cytotoxic and chemotactic activities, furthermore it leads to foam cell formation, a critical step in atherogenesis. The oxidation of LDL is a free radical process and leads to various aldehydic products. The oxidation of LDL is initiated by cells as well as by transition metals like Cu2+. In both cases the oxidation goes through three consecutive phases. The lag-phase is characterized by minimal degradation of PUFAs but a loss of the antioxidants. Thereafter the PUFAs are oxidized to lipid hydroperoxides, which are only intermediates (propagation-phase). These intermediates will decompose to aldehydic products, accompanied by several additional changes in the LDL particle (decomposition phase). For increased macrophage uptake oLDL must reach the late decomposition phase; the presence of lipid hydroperoxides in LDL is not sufficient. It is suggested that binding of aldehydes to free amino groups of Apo B is the reason for macrophage uptake. This is supported by the finding that antibodies against aldehyde-modified LDL are able to recognize oxidized LDL in atherosclerotic lesions. Antioxidants like alpha-tocopherol are able to protect LDL against oxidation. The duration of the lag-phase shows a linear relationship with the content of alpha-tocopherol in LDL. Yet the efficiency of alpha-tocopherol to protect LDL shows strong individual variation. PMID- 1450583 TI - Desialylated low density lipoproteins and atherosclerosis. AB - Oxidative modification of LDL is accompanied by a number of compositional and structural changes, now well known. In addition, other atherogenic modifications of LDL exist, such as desialylation. The present article summarizes the recent data related to desialylated LDL and to the presence of these LDL in blood plasma of patients with coronary atherosclerosis. In addition, this review examines the sensitivity of these LDL to peroxidative stress. PMID- 1450584 TI - Molecular basis of alpha-tocopherol inhibition of smooth muscle cell proliferation in vitro. AB - The molecular events responsible for the inhibition of cell proliferation by alpha-tocopherol have been investigated. Smooth muscle cells in vitro have been shown to be specifically inhibited by alpha-tocopherol with a concomitant inhibition of protein kinase C activity. beta-Tocopherol was inactive, despite its similar radical scavenging activity. The point of inhibition of alpha tocopherol relative to the cell cycle was localized in the late G1 phase. A second effect of alpha-tocopherol observed with smooth muscle cells was the stimulation of protein kinase C biosynthesis in both the S and G2 phases of the cell cycle. The implications of these findings for the onset of arteriosclerosis are discussed. PMID- 1450585 TI - Oxidative damage in Alzheimer's dementia, and the potential etiopathogenic role of aluminosilicates, microglia and micronutrient interactions. AB - While evidence implicating free radical oxidative processes in the etiopathogenesis of Alzheimer's dementia is accumulating, the specific cellular and biochemical mechanisms involved remain to be identified. The potential pathogenic role of microglial cells in neurodegenerative processes is indicated by the finding that purified murine microglial cells exposed in vitro to various model aluminosilicate particles stimulate the generation of tissue-injurious free radical reactive oxygen metabolites. Analogous inorganic aluminosilicate deposits have been reported to occur in the core of the characteristic senile plaques found in the brains of Alzheimer disease subjects. The possible modulation of free radical oxidative activity by antioxidant micronutrients and pharmacological agents, provides a rational basis for further preventative and therapeutic clinical investigations. PMID- 1450586 TI - The role of alterations in free radical metabolism in mediating cognitive impairments in Down's syndrome. AB - Down's syndrome (DS) is a genetic disorder involving an excess of chromosome 21 (trisomy 21) in approximately 96% of the cases and comprises approximately 15% of the population with mental retardation (Heller, 1969). In addition to the constitutional mental deficiencies associated with the syndrome many DS patients develop dementia associated with Alzheimer's disease (AD) in their later years of life (Thase et al., 1984). The genetic locus for Cu,Zn-superoxide dismutase (SOD1), a key enzyme in free radical metabolism, is located on chromosome 21, and the activity level of this enzyme is elevated by approximately 50% in a variety of cells of DS patients (see Kedziora and Bartosz, 1988; Sinet, 1982). Because alterations in free radical metabolism may be involved in neuronal death and may be associated with a number of pathological manifestations of DS, it is important to understand the role of free radical metabolism in cognitive impairments of DS, the topic discussed in this chapter. PMID- 1450587 TI - Evidence for drug metabolism as a source of reactive species in the brain. AB - Several pathways for reactive species formation involving xenobiotic metabolism exist in the brain. They include oxidative activation by different enzymatic systems like cytochrome P-450 and monoamine oxidases, and superoxide radical production issued from reductive xenobiotic metabolism. They may contribute to cellular impairment observed in various physiopathological situations. PMID- 1450588 TI - Anticarcinogenic activities of carotenoids in animals and cellular systems. AB - A large number of studies have indicated that carotenoid pigments act as anticarcinogenic agents in animals treated with either ultraviolet light, ultraviolet light with chemicals, or with chemical carcinogens alone. Although pharmacological doses of cartenoids were used in the early experiments, more recent evidence indicates that relatively small doses can be effective. These studies have been complemented by investigations in bacteria and mammalian tissue, either in cell culture or in organ culture, where it has been demonstrated that various carotenoid pigments can prevent mutagenesis, genotoxic effects, or malignant transformation. It would appear that these effects are intrinsic to the carotenoid molecule, and not necessarily due to the metabolic conversion to retinoids. Partially based on these observations, it has been suggested that carotenoid pigments may function as chemopreventive agents for reducing the risk of cancer in humans. Numerous studies are underway to test this hypothesis. PMID- 1450589 TI - Aging and cancer: plasma antioxidants and lipid peroxidation in young and aged breast cancer patients. AB - The relationship between aging and cancer is complex because the intrication takes place at the cell, the organism and the environment levels. On the other hand, carcinogenesis is a multi-step process, and different mechanisms may be involved in each step. For example, oxidants and antioxidants may play a different role depending upon the phase considered. Tumors in older patients are generally described as slow growing. The difference in tumor aggressiveness between young and older patients is especially obvious in breast cancer patients. The age specificity of some breast risk factors suggests that breast cancer which has been diagnosed in an aged woman was induced late in her life. We address the question whether the characteristics of a senescent organism with regards to oxidant-antioxidant status could be causally related to the slow evolution of tumors in old patients. PMID- 1450590 TI - DNA damage in mammalian cell lines with different antioxidant levels and DNA repair capacities. AB - A wide range of DNA damage is known to be caused by reactive oxygen species (ROS). Defence against the effects of such damage include damage prevention (e.g. antioxidant activity) and the removal of damaged moieties from DNA (DNA repair). Radiation (X-ray) sensitive murine lymphoma (LY) cells were seen to be more susceptible to ROS-induced damage than were radiation resistant cells. This difference was unlikely to be due to the marginally decreased DNA excision repair capacity of the sensitive cells. Radiation sensitive cells did, however, have lower endogenous antioxidant enzyme levels. Thus, the importance of assessing all levels of a cell's response to ROS, in determining the major factors leading to increased mutagen sensitivity, is emphasised. PMID- 1450591 TI - Effect of photooxidation on the eye lens and role of nutrients in delaying cataract. AB - The function of the eye lens is to collect and focus light on the retina. To do so, it must remain clear during the decades of life. Upon aging, lens constituents are damaged and precipitate in opacities called senile cataracts. Laboratory and epidemiologic data indicate that the damage is due in part to light and active forms of oxygen. Antioxidant nutrients - ascorbate, carotenoids, and tocopherol - appear to offer protection against cataract. Fifty million persons worldwide are blind due to cataract, and, in the U.S., there are 1.2 million cataract surgeries performed at an annual cost (including physician visits) of over $3.2 billion. It has been estimated that a 10-year delay in the development of cataract would eliminate the need for half the surgeries. Since it will not be possible to replace most of the damaged lenses, it is essential to determine the efficacy of supplying adequate levels of antioxidant nutrients early in life to preserve lens function. PMID- 1450592 TI - Carotenoids in the retina--a review of their possible role in preventing or limiting damage caused by light and oxygen. AB - Two of the circa 600 naturally occurring carotenoids, zeaxanthin and lutein, the major carotenoids of maize and melon respectively, are the constituents of the macula lutea, the yellow spot in the macula, the central part of the retina in primates and humans. Of the circa ten carotenoids found in the blood these two are specifically concentrated in this area, which is responsible for sharp and detailed vision. This paper reviews the ideas that this concentration of dietary carotenoids in the macula is not accidental, but that their presence may prevent or limit damage due to their physicochemical properties and their capability to quench oxygen free radicals and singlet oxygen, which are generated in the retina as a consequence of the simultaneous presence of light and oxygen. Additionally, in vitro and in vivo animal experiments are reviewed as well as observational and epidemiological data in humans. These show that there is enough circumstantial evidence for a protective role of carotenoids in the retina to justify further research. Some emphasis will be put on age-related macular degeneration (AMD), a multifactorial degenerative retinal disease for which the exposure to light and thus photochemical damage has been suggested as one of the etiological factors. Recent attempts at nutritional intervention in this condition will also be reviewed. PMID- 1450593 TI - Oxidative stress in diabetic retina. AB - The authors describe the alterations usually associated with diabetic retinopathy. They concern the classical thickening of the basal membrane of retinal capillaries and the associated modification of retinal vessel permeability. These alterations correspond to the blood-retinal barrier disruption. The authors then discuss the participation of oxygenated free radicals in the pathogenesis of diabetic retinopathy. They report several experimental studies establishing such a participation and finally describe their own results obtained on a model of retinas isolated from alloxan-induced diabetic rats. After one month of evolution, the electroretinograms (ERG) recorded on isolated retinas from diabetic rats had an amplitude about 20% lower than the controls, whereas after two months of diabetes, this decrease was about 60%. Under these conditions, the authors tested the protective properties of Ginkgo biloba extract (EGb 761) on their model. They observed that in EGb-treated animals (100 mg/kg/day), the ERG had a significantly (p less than 0.001) greater amplitude than untreated animals after two months of diabetes evolution. In conclusion, the authors discuss the possible utilization of a free radical scavenger, such as EGb 761, in the prevention of the retinal impairment in diabetes. PMID- 1450594 TI - Genetic stability and oxidative stress: common mechanisms in aging and cancer. AB - Much evidence indicates that age-related diseases as well as the aging process itself may be a result of genetic instability, resulting in cells changing their proper state of differentiation. Such genetic changes could be of an epigenetic or genetic nature (or both) and suggest that mechanisms acting to stabilize the differentiated state of cells could be major determinants of animal species' general health and longevity. There is also much data indicating that a causative factor in cancer is genetic instability, suggesting the importance of genetic stabilized factors governing the frequency of this disease. Possibly related to these two observations is the good positive correlation between rate of cancer and the rate of aging of different mammalian species. In addition, cells from longer-lived species appear to have a higher intrinsic ability to maintain their proper differentiated state and animals whose life span has been extended by food restriction also have a postponed onset of cancer. These data suggest the possibility that genetic instability may represent a common causative mechanism for both aging and cancer. This suggestion is supported by evidence indicating that oxidative stress can increase cancer frequency and that longer-lived species appear to have a lower oxidative stress state. However, there appears to be a serious lack of evidence indicating that physical and chemical mutagenic agents accelerate aging as they do cancer. For these and other considerations, it is proposed that aging is not a result of genetic instability as are many different age-related diseases. Thus, physiological aging and some age-related diseases could have separate and distinct mechanisms of causation and control. PMID- 1450595 TI - Free radicals and aging of the skin. AB - Cutaneous aging is the result of genetically determined or intrinsic aging superimposed by degenerative changes due to actinic irradiation, also called photoaging. The manifestations of cutaneous aging, as it relates to the perception of age, is caused by ultraviolet light, in particular in those parts of the body exposed daily to solar radiation. Free radical generation in the skin by UV light and from other sources, such as cellular infiltrations or the xanthine oxidase reaction, may be detected by direct and indirect methods. The decrease in antioxidant enzymes and small molecular weight antioxidants such as glutathione, vitamin E and ubiquinone upon exposure to UV light is an indication that the pro-antioxidant balance can be overwhelmed by acute or chronic photo oxidative stress. Antioxidant supplementation is therefore a means for prevention or at least retardation of premature cutaneous aging. PMID- 1450596 TI - Modulators of free radical activity in diabetes mellitus: role of ascorbic acid. AB - Free radical mechanisms are increasingly being implicated in the pathogenesis of tissue damage in diabetes. Various sources of free radicals may modulate oxidative stress in diabetes, including non-enzymatic glycosylation of proteins and monosaccharide autooxidation, polyol pathway activity, indirect production of free radicals through cell damage from other causes, and reduced antioxidant reserve. Ascorbic acid, which may be a principal modulator of free radical activity in diabetes, is shown to be consumed, presumably through free radical scavenging, thus preserving levels of other antioxidants such as glutathione. PMID- 1450597 TI - Possible role of free radicals in the chronic inflammation of the gut. AB - Recent studies have demonstrated that intracolonic administration of trinitrobenzenesulfonic acid (TNB) dissolved in ethanol produces chronic colitis in rats, and that this model shares many features of human inflammatory bowel disease (IBD), particularly Crohn's disease. We investigated the role of free radicals in the pathogenesis of this colitis model. In the early stage of this colitis, antioxidant enzymes (such as superoxide dismutase, glutathione peroxidase) and an antioxidant, alpha-tocopherol, were significantly decreased with the severity of colonic damage. Mn-SOD at a dose of 50000 U/kg attenuated this colitis when preadministered subcutaneously one hour before the induction of colitis. These results suggest that oxygen-derived free radicals may play an important role in this colitis. PMID- 1450598 TI - Age-related variations of enzymatic defenses against free radicals and peroxides. AB - Superoxide dismutase, glutathione peroxidase and catalase are the three main enzymatic systems of defense of the organism against free radicals and peroxides. A survey of the literature shows that no general tendency of evolution of these systems in aging emerges, even if some recent studies in humans demonstrate the existence of a concomitant decrease in most of the antioxidant enzymes in blood of the elderly. The study of the antioxidant systems and their interrelations in the elderly represents a large field of future investigations. PMID- 1450599 TI - Antioxidant status (selenium, vitamins A and E) and aging. AB - Antioxidant status can be evaluated by blood selenium, vitamins A and E. The level of selenium was determined in whole blood, erythrocytes and plasma of 170 French people (70-95 years old) healthy and with intercurrent illness, by using PIXE (proton-induced X-ray emission analysis). These results are discussed with other values from the literature. Plasma levels of vitamins A and E have been measured by HPLC. All data were compared with those obtained for younger subjects. Healthy elderly people residing in a geriatric home received selenium supplements during 1 month. The influence of this supplementation brought to light a deficiency for this trace element. The correlation of aging and nutritional requirements with immune function, heart and cancer death rate is presented and discussed. PMID- 1450600 TI - Inverse correlation between essential antioxidants in plasma and subsequent risk to develop cancer, ischemic heart disease and stroke respectively: 12-year follow up of the Prospective Basel Study. AB - There is accumulating evidence that free radicals may contribute to various diseases such as cancer or cardiovascular disease. Possible health hazards can to some extent be prevented by the body's multilevel defense system against free radicals, which comprises, besides others, antioxidant vitamins. The 12-year mortality follow-up of 2,974 participants of the Basal Study allowed to test the hypothesis that low antioxidant vitamin plasma concentrations (vitamin A, C, E and carotene) were associated with increased death from cancer of various sites and death from atherosclerosis such as ischemic heart disease and stroke, respectively. For the analysis 204 cancer cases, 132 fatalities from ischemic heart disease (IHD) and 31 deaths from cerebral vascular disease were available. Cancer mortality. Overall mortality from cancer was associated with low mean plasma levels of carotene adjusted for cholesterol (p less than 0.01) and of vitamin C (p less than 0.01). Bronchus and stomach cancers were associated with a low mean plasma carotene level (p less than 0.01). Subjects with subsequent stomach cancer had also lower mean vitamin C and lipid-adjusted vitamin A levels than survivors (p less than 0.05). Calculating the relative risk with exclusion of mortality during the first two years of follow-up, low plasma carotene was associated with an increased risk for bronchus cancer (RR 1.8, p less than 0.05), and the small number of stomach cancer cases (RR 2.95, p less than 0.05) low plasma levels of carotene and vitamin A with all cancer types (RR 2.47, p less than 0.01), and low plasma retinol in older subjects (greater than 60 years) with lung cancer (RR 2.17, p less than 0.05). Studies in other cohorts with a poor vitamin E status revealed an increased risk of subsequent cancer at low vitamin E levels as well. It is concluded that low plasma levels of all major essential antioxidants are associated with an increased risk of subsequent cancer mortality. Cardio-vascular mortality. Plasma carotene concentration below quartile 1 was associated with an increased risk for IHD (RR 1.53, p = 0.02). The same was true for low levels of both carotene and vitamin C (RR = 1.96, p = 0.022). The risk of cerebrovascular death was elevated in subjects with low carotene in the presence of low vitamin C plasma concentration (RR 4.17, p less than 0.01). These data confirm and extend recent findings on an inverse correlation of beta-carotene and vitamin C respectively to CVD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1450601 TI - Vitamin E requirement in relation to dietary fish oil and oxidative stress in elderly. AB - A growing body of evidence shows that oxygen radicals and other products of free radical reactions are involved in aging and age-related degenerative diseases. Recent studies have suggested that fish oils (FO) have a potentially beneficial effect on age-associated diseases. Consumption of FO may increase requirement for vitamin E, especially under conditions where oxidative stress is increased. Vitamin E requirement increases with increased intake of dietary polyunsaturated fatty acids (PUFA). This relationship may be exaggerated in elderly subjects. Our studies, as well as those of others, have shown that plasma lipid peroxides are significantly higher in older subjects compared to young subjects. Thus, in conditions where the percentage of highly unsaturated fatty acid increases in the membrane, older subjects may be more susceptible to oxidative damage. In a series of human studies, we found that older women, receiving FO supplements for 3 months exhibited a greater increase in plasma PUFA compared to young subjects. By substituting membrane fatty acids with the potentially unstable (n-3) fatty acids of FO, older subjects were found to be at greater risk of oxidative stress than young subjects. In addition, when exposed to eccentric exercise-induced oxidative stress, older men, receiving vitamin E supplements for 48 days, exhibited significantly lower levels of lipid peroxides in urine compared to placebo control. These data indicate that older subjects are more susceptible to oxidative stress and may benefit from the antioxidant protection provided by vitamin E. PMID- 1450602 TI - Vitamin C and vitamin E--synergistic interactions in vivo? AB - The synergistic relationship between ascorbic acid (vitamin C) and alpha tocopherol (vitamin E) in the inhibition of lipid peroxidation has been known for some time and is now well established in vitro systems. The possibility that ascorbic acid may also reduce tocopheroxyl radicals in vivo is a subject of some interest and speculation. Although not all experiments have failed to suggest a synergistic antioxidant interaction, recent data indicate that the postulated synergism between these vitamins might be relatively unimportant compared with other metabolic processes. PMID- 1450603 TI - The threshold of age in exercise and antioxidants action. AB - Physical activity and exercise are important factors in determining the quality of life in old animals and humans. With age there is a slow but significant reduction in muscle mass and ability to perform certain physical activities. This may be due to changes with the age of muscle composition and protein turnover, as well as decrease of trophic influence in neural control of muscles of old individuals. Exercise in general was shown to improve muscle performance even in old age. However a concept of threshold of age in exercise was advanced forward in the 1970s. Accordingly, the idea was that for a given exercise of a particular duration and intensity there is a certain age beyond which this exercise may not have a positive influence, but can become detrimental to the exercising animal or human. Recent studies on the effect of antioxidants such as Vitamins C and E and selenium have shown that these agents could decrease the free radical associated muscle damage caused by extensive exercise. Thus, administration of these antioxidants especially vitamins C and E may reduce the oxidative damage due to exercise, and may alter the threshold of age by delaying it to an older age. PMID- 1450604 TI - Antioxidant therapy in the aging process. AB - A total of 1,265 patients with age-related diseases such as diabetes, arthritis, vascular disease and hypertension as well as 1,100 persons in diminished health without apparent disease, were treated with the metal chelator EDTA and antioxidants such as vitamin C, E, beta-carotene, selenium, zinc and chromium. Good results were observed in the majority of patients. This is encouraging for the initiation of controlled clinical trials. PMID- 1450605 TI - Oxygen-induced mitochondrial damage and aging. AB - Although the views of Harman and Gerschman provide a reasonable explanation for many of the effects of aging, they fail to explain why many cell types, from amoebae to mammalian spermatogonia, do not show a time-related involution, while other cells (especially the neurons) change with age. We feel that a better understanding of senescence (from the molecular to the organ and organismic levels) can be gained by integrating the free radical theory of aging with the classic concepts of Minot and Pearl on the role of cell differentiation and metabolic rate in, respectively, triggering and pacing senescence. In agreement with the above, we maintain that aging is the non-programmed but unavoidable "side effect" of oxy-radical damage to the membrane and genome of the mitochondria of irreversibly differentiated cells. If oxy-radical damage to mtDNA occurs, it will block the rejuvenation of the mitochondrial population by the process of organelle division, thus leading to bioenergetic decline and cellular death. PMID- 1450606 TI - Instabilities of metabolic regulations in aging. AB - 1) That non-invasive NMR and optical methods can a) quantify the work stress on mitochondria for ATP production, and b) indicate the tissue O2 tension in the capillary bed that is responsible for the rate of radical generation. 2) That free radical damage to mitochondrial function can be quantified by reciprocal plots of inverse slope giving the extrapolated Vm of mitochondria. 3) That a particular genetically deficient individual requiring high dosages of menadione has survived over 9 years. 4) That mitochondrial deficiency leads to an exercise hyperoxia. PMID- 1450607 TI - Lipofuscinogenesis in a model system of cultured cardiac myocytes. AB - Lipofuscin, or age pigment, is a yellowish-brown, autofluorescent, protein, and lipid containing pigment that accumulates in the lysosomal vacuome of a variety of post-mitotic cells in man and animals during aging. Lipofuscin seems to be an end product of peroxidation, fragmentation and polymerization of proteins and lipids. Protein and lipid containing materials are regularly sequestered to the lysosomal system by means of endocytosis and autophagocytosis. Lysosomes and acidified endosomes constitute cellular compartments where iron for short periods of time may exist in reactive form allowing for peroxidative processes. The importance was demonstrated in model systems of cultured cells subjected to oxidative stress and augmented amounts of FeCl3 in the culture medium. This combination was considered to result in increased intracellular, mainly mitochondrial, production of hydrogen peroxide as well as increased intralysosomal concentration of iron. One of the results of this situation was dramatically increased lipofuscinogenesis. PMID- 1450608 TI - Cellular clones and transgenic mice overexpressing copper-zinc superoxide dismutase: models for the study of free radical metabolism and aging. AB - Down's Syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of the chromosome numbered 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain where the occurrence of Alzheimer's disease (AD) is observed in all trisomy 21 patients over the age of 35. Elucidation of the biological mechanisms leading to brain aging in DS might provide new insight into the understanding of brain aging and AD in normal people. Copper-zinc superoxide dismutase (CuZnSOD) is one of the genes encoded by chromosome 21. As a consequence of gene dosage excess, CuZnSOD activity and protein are increased by 50% in all DS tissues. The level of CuZnSOD protein and mRNA is particularly high in hippocampal pyramidal neurons susceptible to degenerative processes in AD and in dopaminergic melanized-neurons vulnerable in Parkinson's disease. Increased CuZnSOD activity in these age-related neurodegenerative disorders might result in H2O2 overproduction and subsequently promote peroxidative damages within cells. Increase of seleno-dependent glutathione peroxidase (Se-GPx) in DS cells supports this concept. In order to test this hypothesis, cell and animal models of CuZnSOD overexpression have been designed. In cells transfected with the human CuZnSOD gene, and increased Se-GPx activity is observed, a situation which mimics DS. In mice transgenic for the human CuZnSOD, the expression pattern of the transgene in the brain is similar to that in humans, and we can observe an increased peroxidation in this tissue. These data, like others in the literature, support the hypothesis that excess CuZnSOD induces an imbalance in the regulation of oxygen-derived free radical production which might result in peroxidative brain damage and possibly contribute to accelerated aging and age-related neuropathology. PMID- 1450609 TI - The importance of antioxidant enzymes in cellular aging and degeneration. AB - Aerobic cells contain various amounts of the three main antioxidant enzymes: superoxide dismutase (SOD), catalase and GSH peroxidase. These three enzymes are necessary for cell survival since inhibition of their activity leads to the arrest of cell mitosis and to cell death. Amongst them, GSH peroxidase was shown to be more efficient than catalase and much more than SOD. This result was obtained by comparing the cell protection against oxidative stress after their microinjection in the cytoplasm. With age, the level of these antioxidant enzymes does not change in several experimental models, so that it is not possible to explain the aging process by a lack of protection due to a decrease in the activity of these three enzymes. However, tissues and cells are more susceptible to free radical attacks with age. In order to understand the importance of free radicals in this process, we have to distinguish between their respective effects on cell mitosis, cell death and cell aging. The effects on mitosis and cell death are well described, and the results clearly show a threshold of response which is determined by the antioxidant content of the cell. There is now evidence that short free radical stresses can also speed up the aging of in vitro cultured human fibroblasts. However, such effects are not typical of free radicals but are also obtained with many other deleterious substances so that free radicals have to be considered as one amongst other factors responsible for influencing the evolution of a cell to an older stage or to cell death. The lowering of the general metabolism and of the free energy in old cells are probably the main factors responsible for the increased susceptibility of these cells to stresses such as oxidative stresses. PMID- 1450610 TI - The importance of molecular size in the pathophysiology of CSF proteins. PMID- 1450611 TI - Increased serum N-acetyl-beta-D-glucosaminidase and alpha-D-mannosidase activities in obese subjects. AB - We have studied N-acetyl-beta-D-glucosaminidase and alpha-D-mannosidase activities in human sera from 35 control subjects, 47 normo- and hyperinsulinemic obese persons, and 12 diabetic patients after a fasting period of 12 h and at 30, 60, 90, and 120 min after an oral glucose overload. The results show a significantly higher activity of these 2 enzymes in obese subjects and diabetic patients, of similar magnitude, especially in those obese persons with a higher grade of obesity. Moreover, the activity of these glycosidases decreases in a similar way in all these 3 groups after the oral glucose overload. PMID- 1450612 TI - Effects of calcium channel blocking and atrial stimulation on QT time during hyper- and normocalcemia in man. AB - We investigated how calcium channel blocking agents modify the known decrease of QT time with increasing heart rate and calcium level. Furthermore, we examined how the influence of calcium channel blocking agents is modulated by atrial stimulation. To answer these questions, we measured the QT time both at a spontaneous heart rate and during atrial stimulation with 90 and 110 beats/min before and after intravenous administration of 5 mg verapamil in 23 patients with primary hyperparathyroidism, pre- and postoperatively. Atrial stimulation increased the frequency-related standard values of QT time. The spontaneous heart rate (HR) was influenced by neither the calcium level nor verapamil. The statistically significant correlations QT vs. HR and QT vs. Ca were reduced by verapamil, which indicated its influence. However, this effect did not achieve statistical significance. PMID- 1450613 TI - Comparison of dietary intakes in four selected European populations. AB - The composition of diet and food intakes in four selected European populations were compared. Dietary data (from the World Health Organization Project on Monitoring Trends and Determinants in Cardiovascular Disease) were measured by record methods and were available for middle-aged men in Finland (n = 653), France (n = 1128), Northern Ireland (n = 356), and southern Germany (Augsburg region; n = 899). Nutritional variables--which are independent of the absolute energy intake, such as the percentage supply of energy from macronutrients and the ratio of polyunsaturated to saturated fatty acids--were on the whole similar. However, striking differences were found in food intake and in the percentage supply of fat from different foods. The results indicate that detailed knowledge of consumption figures is necessary to develop prudent and acceptable nutrition intervention programs. PMID- 1450614 TI - Positive correlation between aortic valve pressure gradient and mitochondrial respiratory chain capacity in hypertrophied human left ventricle. AB - The effect of chronic left ventricular pressure overload on the activities of mitochondrial respiratory chain enzymes was investigated in myocardial biopsies from the left ventricular apex of 13 patients undergoing aortic valve replacement for aortic valve stenosis. Transvalvular pressure gradients measured by left sided heart catheterization ranged from 52 to 100 mmHg. The specific activity of mitochondrial respiratory chain enzyme complexes I+III (antimycin A sensitive NADH cytochrome c oxidoreductase) and the myocardial concentrations of coenzyme Q10 (CoQ10) increased significantly (P < 0.05) with increasing aortic valve pressure gradient. In contrast, the specific activities of complex IV (cytochrome c oxidase), succinate dehydrogenase, and citrate synthase, a mitochondrial matrix enzyme, showed no significant correlation with the pressure gradient. Since CoQ10 is the rate-limiting compound of the activity of complexes I+III but not of cytochrome c oxidase, succinate dehydrogenase, or citrate synthase, these data suggest that the increase in the activity of complexes I+III is due to the increase in CoQ10 content. PMID- 1450615 TI - Induction of the fed pattern of human exocrine pancreatic secretion by nutrients: role of cholecystokinin and neurotensin. AB - The aim of the present study was to assess the role of cholecystokinin and neurotensin in converting the cyclical interdigestive pattern of pancreatic secretion into the non-cyclical fed pattern. Six healthy male volunteers were studied on 4 separate days. During each experiment a mixed liquid meal or solutions of individual nutrients were perfused intraduodenally for 180 min at 2 ml/min. The mixed meal contained 4.3 g glucose, 2.0 g fractionated soya oil, and 1.7 g casein hydrolysate per 100 ml, which delivered a caloric load of 0.9 kcal/min into the duodenum. The isocaloric and isotonic solutions of individual nutrients contained 44.5 g glucose, 17.8 g fractionated soya oil, or 44.5 g hydrolysed serum bovine albumin per liter and delivered 0.36 kcal/min into the duodenum. Duodenal aspirates and blood samples were collected at regular intervals for determination of pancreatic enzyme outputs and plasma levels of cholecystokinin and neurotensin, respectively. The mixed meal converted the cyclical interdigestive secretory pattern into the noncyclical fed pattern whereas none of the three individual nutrients abolished the interdigestive pattern. Not only the mixed meal but also lipid and protein perfusion consistently stimulated cholecystokinin release. Integrated incremental cholecystokinin release amounted to 32.3 +/- 9.9 pg/ml x 180 min with the mixed meal, 23.2 +/- 6.5 with lipid perfusion (P < 0.05 versus mixed meal) and 13.4 +/- 3.8 with protein perfusion (P < 0.05 versus mixed meal). The carbohydrate solution did not significantly release cholecystokinin. None of the duodenal perfusates raised neurotensin plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450616 TI - Long-term follow-up of renal transplantation in type 1 and type 2 diabetic patients. AB - This study evaluated the long-term outcome of renal transplantation in type 1 (n = 25) and type 2 (n = 18) diabetic patients. Overall postoperative survival at 1 year was 69% in type 1 diabetes and 75% in type 2; at 5 years it was 62% in type 1 diabetes and 58% in type 2. Death was due mainly to cardiovascular disease (60%) and septic gangrene (20%). Outcome was examined in terms of graft function, which was poor in the majority (86%) of patients who died. Patients with fatal outcome suffered major vascular complications prior to renal transplantation and frequently had impaired graft function. Metabolic control was better in patients with good graft function (HbA1c < 6.2%) than in those with poor or no function of kidney transplant (HbA1c > 9.8%). In the absence of severe vascular complications renal transplantation may be the treatment of choice for both type 1 and type 2 diabetic patients with end-stage renal disease. Otherwise, renal transplantation is not able to improve the prognosis of patients with a history of severe vascular complications prior to renal replacement therapy. PMID- 1450617 TI - Q fever endocarditis: diagnostic approaches and monitoring of therapeutic effects. AB - The scope of current diagnostic methods for Q fever endocarditis includes serology, direct demonstration of Coxiella burnetii in the resected heart valve tissue, and animal inoculation studies. Illustrated by a clinical case report, the different methods are presented and discussed. Serology represents the primary method, using the techniques of complement fixation, indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). The latter two techniques allow the detection of immunoglobulins G, M, and A to the phase I and II antigens of C. burnetii. After cardiac surgery, we visualized C. burnetii on smears and specifically stained it on histologic sections of the resected heart valve by light and electron microscopic immunohistochemistry. In addition, seroconversion in animals after inoculation with valve specimens confirmed the presence of C. burnetii in the heart valve. The antibody titers determined by ELISA correlated well with the patient's clinical course during the treatment period. Therefore it is suggested that its usefulness for monitoring the efficacy of antimicrobial agents in patients with Q fever endocarditis should be further evaluated. PMID- 1450618 TI - Successful treatment of primary adrenal insufficiency due to malignant non Hodgkin's lymphoma. AB - Although the adrenal glands are frequently the site of tumor metastases, adrenal insufficiency is exceedingly rare. We report on a patient with high-grade B-cell centroblastic lymphoma who initially presented with right axillary lymphadenopathy and bilateral adrenal masses. Four months after axillary lymphadenectomy the patient developed overt signs of Addison's disease. He recovered promptly after initiation of hormone replacement therapy and bilateral adrenalectomy. At present, 16 months after additional chemo- and radiation therapy the patient is considered free of tumor. To our knowledge this is the first report on a patient who presented with adrenal insufficiency in the course of non-Hodgkin's lymphoma and who was successfully treated. Demonstrating this case, we would also like to stress that the development of adrenal insufficiency does not necessarily indicate widespread tumor manifestation in patients with non Hodgkin's lymphoma. PMID- 1450619 TI - Renal long-term effects of calcium antagonist treatment in patients with diabetes mellitus. AB - Although calcium antagonists have long been introduced into antihypertensive treatment, little is known of their renal long-term action in patients with diabetes mellitus, diabetic nephropathy, or hypertension. Much of the current information concerning this issue is from short-term studies. While urinary albumin excretion, a major indicator of glomerular damage in patients with diabetes mellitus, remains unchanged or even increases during short-term calcium antagonist treatment in type 1 diabetic patients, it is mostly reduced in type 2 diabetic patients, especially by diltiazem and nicardipine. There have been discrepant observations in studies lasting 6-months or longer. In many of the studies, urinary albumin excretion is not decreased by calcium antagonist treatment, although blood pressure is well controlled. Albuminuria is markedly reduced, however, after nitrendipine or diltiazem treatment. While calcium antagonists such as diltiazem, nicardipine, or nitrendipine may be as efficacious as converting enzyme inhibitors in preventing the progression of diabetic kidney disease in diabetic patients, the beneficial efficacy of others is less apparent. Reduced albuminuria may be more difficult to attain in macroalbuminuric patients with advanced nephropathy. However, considerations on the potential effects of calcium antagonist long-term treatment on cardiovascular morbidity or mortality in diabetic patients should not be overlooked when their renal action is under discussion. Thus, further studies are needed to define the role of calcium antagonists more precisely in the long-term treatment of diabetic patients with hypertension or diabetic nephropathy. PMID- 1450620 TI - Three cases of malignant neoplasm, pneumonitis, and pancytopenia during treatment with low-dose methotrexate. AB - A 77-year-old man with chronic obstructive pulmonary disease was treated with low dose methotrexate (7.5-15 mg per week). After 15 months a diagnosis of urothelial carcinoma of the bladder was made; after a further 6 months pneumonitis and pancytopenia developed. The patient died due to massive pulmonary hemorrhage. A malignant teratoma was diagnosed in a 65-year-old asthmatic man 16 months after initiation of methotrexate therapy (15 mg per week). The patient died 4 months later due to fulminant progression of the neoplasm. A third malignant neoplasm (dermal squamous cell carcinoma) was seen in a 64-year-old woman with rheumatoid arthritis after 13 months treatment with 7.5 mg methotrexate per week. These three cases, while obviously not proving a causal relationship between long-term treatment with low-dose methotrexate and development of malignant neoplasm, do call for stringent treatment criteria, close surveillance, and prospective studies. PMID- 1450621 TI - HLA-DRB3 gene alleles in Caucasian patients with Graves' disease. AB - Graves' disease (GD) is a human leukocyte antigen (HLA) linked organ-specific autoimmune disease. In German GD patients the disease is associated with HLA specificities of the HLA-DRw52 family (HLA-DR3, -DR5, and DR6; HLA-DRB3 positive HLA haplotypes). Recently, a strong association with a HLA-DRB3 restriction fragment length polymorphism gene has been described. To study HLA-DRB3 alleles and their association with the disease, a large cohort of controls (n = 3724) and GD patients (n = 304) was analyzed. HLA-DR allelic combinations revealed an increase in HLA-DR3/DR5 heterozygous patients (relative risk 2.9; P < 0.001). HLA DRB3 alleles, as defined by DNA typing in HLA-DR matched groups revealed a significant increase in DRB3*0101 homozygosity (relative risk 17.5; P < 0.001) in HLA-DR3 homozygous patients. In GD patients with ophthalmopathy (grade II or higher, according to Werner) DRB3*0101/*0202 heterozygosity revealed an increased relative risk of 5.5 (P < 0.001). Non-HLA-DR3 homozygous, DRB3*0101/*0202 heterozygous patients were at the highest risk for endocrine ophthalmopathy (relative risk 10; P < 0.001). Our data, based on DNA typing methods of HLA-D genes, provide evidence that the susceptibility is strongly associated with HLA DRB3 genes. PMID- 1450623 TI - Failure to detect any effect of amalgam restorations on peripheral blood lymphocyte populations. AB - Dental amalgam has been considered to have adverse side effects on the immune system. Reports have been contradictory, indicating both an increase and a decrease in peripheral blood lymphocyte counts associated with amalgam restorations. We investigated two groups of patients, one of which was treated with amalgam restorations for the first time. In the other group, all existing amalgam fillings were removed. Prior to and after treatment, we determined the absolute and relative numbers of granulocytes, lymphocytes, monocytes, T cells, B cells, cytotoxic T cells, helper T cells and natural killer cells. In addition, functional investigations of T cells were performed. We failed to find any effect of amalgam restorations on the immune system in terms of the parameters investigated. PMID- 1450622 TI - Immediate and long range effects of the uptake of increased amounts of arachidonic acid. PMID- 1450624 TI - Caries susceptibility and renal excretion of calcium. AB - Clearance studies were performed for 2 days in two groups of age-matched young female volunteers: those with low caries prevalence and those with high caries prevalence. Both groups were kept on a low-calcium diet for 1 week and received 0.5 g calcium at the beginning of the second day. In both groups, glomerular filtration rate, urinary flow rate and renal excretions of sodium, calcium, and phosphate were subject to significant circadian variations. In both groups the administration of calcium led to a significant increase in renal excretion of sodium and calcium and a significant decrease in that of phosphate. On the first day, calcium excretion was significantly greater in those with low caries prevalence than in those with high caries prevalence, pointing to altered calcium homeostasis in this group. PMID- 1450625 TI - Esophageal dysfunction in diabetes mellitus: is there a relation to clinical manifestation of neuropathy? AB - In a prospective study, we evaluated 33 diabetic patients [type I (n = 8) and type II (n = 25)]. Esophageal motor functions were examined by registering clinical symptoms and by performing esophageal manometry. We also investigated peripheral and autonomic neuropathy. In diabetics, the lower and upper esophageal sphincter pressure and amplitudes of peristaltic waves were reduced. Compared with controls (n = 30), in diabetics the esophageal peristaltic velocity was reduced significantly, and the duration of contractions were decreased as well. Multipeaked waves were uncommon in diabetics, while non-propulsive contractions were seen more often. No correlation was found between esophageal dysfunction and peripheral or autonomic neuropathy. Some 60% of diabetics reported esophageal symptoms; however, no relationship between these symptoms and the extent of dysfunction in esophageal motility was found. PMID- 1450626 TI - Disturbed calcium metabolism in subjects with elevated diastolic blood pressure. AB - Essential hypertension has been associated with disturbed calcium metabolism, but the available data are controversial. We measured parameters of calcium metabolism in groups of untreated male subjects (n = 78) with elevated diastolic blood pressure (101 +/- 6 mmHg, mean +/- SD) and age-matched male subjects (n = 79) with low diastolic blood pressure (62 +/- 4 mmHg). The participants of the study were drawn from a random population sample. Subjects with high diastolic blood pressure had significantly higher carboxy-terminal parathyroid hormone (PTH) plasma concentrations than controls with low diastolic blood pressure (median 114 vs. 43 pmol/l, P less than 0.01). The 25-hydroxyvitamin D and 1,25 dihydroxyvitamin D concentrations were comparable in both groups. Individuals with high diastolic blood pressure had significantly lower total serum calcium (2.41 +/- 0.10 vs. 2.47 +/- 0.10 mmol/l, mean +/- SD; P less than 0.01). PTH concentrations were correlated with diastolic pressure (r = -0.39, P less than 0.001). The data are compatible with increased parathyroid activity despite unchanged concentrations of vitamin D metabolites in human hypertension. PMID- 1450627 TI - Sulfadiazine therapy for toxoplasmosis in heart transplant recipients decreases cyclosporine concentration. AB - Toxoplasmosis may cause serious problems after organ transplantation. For treatment of active infection, pyrimethamine combined with a sulfonamide is recommended. During oral sulfadiazine therapy, a significant decrease in cyclosporine concentrations was observed in three heart transplant recipients. This interaction has not been reported previously. PMID- 1450628 TI - Pentoxifylline influences acute-phase response in acute myocardial infarction. PMID- 1450629 TI - Molecular mechanisms involved in the etiology and pathogenesis of autoimmune diseases. PMID- 1450630 TI - Current status of HLA matching in renal transplantation. The Collaborative Transplant Study. AB - The impact of HLA compatibility on the success rate of kidney transplants was studied in over 80,000 recipients of primary transplants. The transplants were done from 1982 to 1991 at over 300 transplant centers in 43 countries. The results show that matching the HLA chromosomes in related donor transplants has a striking influence. It is also important that matching for individual HLA antigens in cadaver transplants provides a highly significant improvement in graft survival (P less than 0.0001). After 5 years, matched grafts have a survival rate approximately 20% higher than completely mismatched grafts. The matching effect is particularly strong in presensitized and second graft recipients. There is now direct evidence that even if it is necessary to transport well-matched kidneys a long way, they have a significantly higher success rate than locally transplanted poorly matched kidneys. New data based on molecular technology show that the precise identification of HLA-DR antigens by DNA typing further improves the success rate of HLA-matched transplants. PMID- 1450631 TI - Progress towards a molecular understanding of cyclosporin A-mediated immunosuppression. AB - Immunosuppressive drugs like cyclosporin A (CsA), FK506 and rapamycin exert their immunosuppressive potential primarily by interfering with the activation and proliferation of T cells. These substances bind to intracellular receptor proteins, called immunophilins. Immunophilins are ubiquitous and abundant proteins, found in all prokaryotic and eukaryotic cells investigated, as well as in many subcellular compartments. Immunophilins display an inherent enzymatic activity, the prolyl-peptidyl cis-trans isomerase (PPIase). The eukaryotic PPIases are inhibited upon the binding of immunosuppressants. In addition, the complex of immunophilins and CsA or FK506 acquires a new activity, namely the binding and inhibition of the cytoplasmic Ca(2+)-binding phosphatase calcineurin. This inhibition is postulated to prevent the proper assembly and nuclear positioning of the transcription factor NF-AT (nuclear factor of activated T cells). The correct DNA binding of NF-AT to regulatory elements of the interleukin 2 (IL-2) promoter normally contributes to the transcriptional activation of this gene. Thus, immunosuppressive drugs prevent T-cell activation by interfering with Ca(2+)-dependent signal transduction pathways which regulate gene activities. PMID- 1450633 TI - Autosomal dominant polycystic kidney disease: from molecular genetics to the patients. AB - One of the gene loci (PKD1) responsible for autosomal dominant polycystic kidney disease was located in 1985 to the short arm of chromosome 16. The clinical consequences of this finding are analyzed. Genetic heterogeneity has been demonstrated since 5%-15% of the families inherit a non-PKD1 mutation. Progress in molecular genetics allows better classification of patients with some atypical manifestations, e.g., those with early renal failure or those with congenital hepatic fibrosis. Identification of the gene(s) and of their defects will provide further progress. PMID- 1450632 TI - Towards understanding the pathophysiology of chronic rejection. AB - Chronic allograft rejection is the major reason why allografts are lost. While only 2%-3% of all allografts are lost during the first year to irreversible acute rejection, approximately 6%-7% are lost during each subsequent year to chronic rejection. The major manifestation of chronic rejection in all organs is persistent perivascular inflammation and allograft arteriosclerosis. Bearing this in mind, we have developed a model to investigate the pathophysiology of allograft arteriosclerosis using aortic transplantations between inbred rat strains. The results obtained thus far indicate that several different inflammatory cascades are operative within the vascular wall during allograft arteriosclerosis. The relative importance of these different cascades, and particularly the role of growth factors as final effectors, has not yet been defined. Attempts to suppress allograft arteriosclerosis under experimental conditions have already met with some success: under conditions where no immunosuppression is provided we have been able to delay the process by at least 3 months, though we have not been able to block it indefinitely. It may be expected, however, that once the inflammatory cascades leading to smooth muscle cell replication in the allograft media and their influx into the intima are better defined, more specific approaches to the inhibition of allograft arteriosclerosis will be developed. PMID- 1450634 TI - Autosomal recessive polycystic kidney disease. AB - Autosomal recessive polycystic kidney disease is a rare inherited disorder which usually becomes clinically manifest in early childhood, whereas autosomal dominant polycystic kidney disease usually is a disorder of adult onset. With increasing knowledge and improving diagnostic techniques, it becomes evident that the spectrum of both entities is much more variable than generally known. The presentation of autosomal recessive polycystic kidney disease at later ages and survival into adulthood have been reported. The diagnostic criteria, clinical course, genetics and differential diagnosis of autosomal recessive polycystic kidney disease will be presented. PMID- 1450635 TI - The nephronophthisis complex: clinical and genetic aspects. AB - Familial juvenile nephronophthisis (NPH) and medullary cystic disease (MCD) are hereditary forms of early-onset chronic renal failure caused by the bilateral formation of cysts at the corticomedullary junction of the kidney. Polyuria, polydipsia, anemia, and growth retardation precede end-stage renal failure. The absence of edema and hypertension frequently leads to a delay in the diagnosis and commencement of therapy. The condition is a major cause of end-stage renal disease (ESRD) in children, accounting for 10%-25% of these patients. About 300 cases of NPH or MCD have been described. Although they are almost indistinguishable clinically and pathologically, the two conditions are separated by a characteristic age of onset (11.5 years in NPH vs. 28.5 years in MCD) and by the mode of inheritance (autosomal recessive in NPH vs. autosomal dominant in MCD). An association of NPH with retinitis pigmentosa is known as the Senior Loken syndrome (SLS). Hepatic fibrosis, skeletal defects, and central nervous system abnormalities have been described in association with NPH but are typically absent in MCD. Since the pathology of NPH and MCD is similar, the term "nephronophthisis complex" has been introduced to summarize the related diseases. At present, there are no means of identifying heterozygotes, conducting prenatal diagnosis, or screening children in affected families. The histologic changes of NPH are characteristic but not specific for the disease. Cysts of 1-15 mm in diameter, located primarily at the corticomedullary junction, are seen in 70% of the patients. Light microscopy reveals a chronic sclerosing tubulo-interstitial nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450636 TI - Molecular aspects of Alport's syndrome. AB - We review the recent progress achieved on the understanding of the molecular basis of Alport's syndrome. This inherited disease is defined as progressive nephritis with sensorineural hearing loss. In 80%-85% of the families, inheritance is compatible with X-linked dominant transmission, whereas in the remaining cases autosomal dominant transmission is assumed. Histology studies demonstrated that the main defect is within the glomerular basement membrane (GBM). In addition, evidence for an altered GBM antigenicity came from immunofluorescence studies which showed a reduced or absent binding of anti-GBM autoantibodies or monoclonal antibodies to the "Goodpasture antigen" in some families. Subsequent studies added substantial evidence that Alport's syndrome is a type IV collagen disease. Genetic linkage analyses coherently identified an Alport locus at the X-chromosomal region Xq21.3-22. Recently, a previously unknown alpha 5 chain of type IV collagen was identified, and the corresponding gene was also mapped to Xq22. Subsequent studies on Alport families by various groups identified more than 25 COL4A5 lesions. Segregation in linkage with the Alport phenotype could be shown in large kindreds. Mainly deletions and only a few point mutations were described. Most lesions reported so far are heterogeneous. We were able to identify two deletions and one point mutation involving a 3' splice site in 20 Alport families from Germany. One of the patients with a COL4A5 deletion and the patient with the splice site mutation developed anti-GBM antibodies after renal transplantation. In contrast, no COL4A5 lesions have been found in 2 further patients with posttransplant anti-GBM nephritis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450637 TI - Oscillations: a key event in transformed renal epithelial cells. AB - Intracellular pH (pHi) plays a critical role in the entry of cells into the DNA synthesis phase of the cell cycle. Alterations in pHi may contribute to abnormal proliferative responses such as those seen in tumorigenic cells. We observed that alkaline stress leads to genomic transformation of Madin-Darby canine kidney (MDCK) cells. Transformed cells (F cells) form "foci" in culture, lack contact inhibition, and are able to migrate, typical characteristics of dedifferentiated tumorigenic cells. F cells exhibit spontaneous biorhythmicity. Rhythmic transmembrane Ca2+ flux activates plasma membrane K+ channels and Na+/H+ exchange. This leads to periodic changes of membrane voltage and pHi at about one cycle per minute. We conclude that endogenous oscillatory activity could be a trigger mechanism for DNA synthesis, proliferation, and abnormal growth of renal epithelial cells in culture. PMID- 1450638 TI - The inflammatory function of renal glomerular mesangial cells and their interaction with the cellular immune system. AB - The autoimmune nature of chronic progredient glomerular diseases has been well established. Like in other chronic inflammatory diseases, the active role of organ-borne cells has become increasingly apparent--both for the inflammatory process and for the initiation and perpetuation of the immune reaction. In most forms of glomerulonephritis, intrinsic glomerular mesangial cells are likely candidates to come into intimate contact with immune cells such as monocytes or lymphocytes. On the basis of cell culture studies we would like to integrate the current knowledge available about the responsiveness of mesangial cells to inflammatory agents and the resulting secretory capacity and, moreover, their possible role in sustaining chronic inflammatory injury and autoimmune reactions through a direct interaction with lymphocytes. Apart from being responsive to physiological stimuli such as angiotensin II, glomerular mesangial cells are predominantly activated by agents related to inflammation. This includes exogenous substances such as the components of gram-negative bacteria and an array of highly potent immunological stimuli like antigen-antibody complexes, activated complement, or various cytokines. The transformation of resting mesangial cells to proliferating cells with an accompanying expansion of their secretory profile and responsiveness is due to mediators like platelet-derived growth factor, transforming growth factor, and others. Numerous low-molecular weight substances (O2-, H2O2, NO, platelet-activating factor, eicosanoids), proteins (proteinases, matrix components, interleukins 1 and 6, colony stimulating factors, growth factors), and cell-surface molecules released or expressed by mesangial cells participate in the inflammatory process. Among these products interleukin 1 and/or 6, class II major histocompatibility antigen and integrins also support an interaction with the cellular immune system. It has been well documented that mesangial cells induced in vitro by recombinant T-cell lymphokines, such as interferon-gamma, do express MHC II and ICAM-1 and could function as antigen-presenting cells. However, and perhaps more interestingly, our own recent experiments with cocultures of syngeneic mouse lymphocytes and mesangial cells have demonstrated that T-cells are directly activated by cultured mesangial cells, thus resembling a mesangial cell-specific autoimmune reaction. In parallel to clinical studies searching for a mesangial autoantigen these experiments might help to elucidate the mechanisms of initiation and perpetuation of mesangial cell-dependent autoimmune glomerulonephritis. PMID- 1450639 TI - The glomerular mesangium: capillary support function and its failure under experimental conditions. AB - We present a structural analysis of the ability of the biomechanical unit consisting of mesangium and glomerular basement membrane to maintain normal capillary architecture in the face of mechanical challenges due to high intraglomerular pressures. Capillary support function may be considered in terms of the stabilization of local form (development of wall tension against capillary dilation) and global form (centripetal fixation of capillary loops to maintain higher order form). The pathologic consequences of the loss of this support are illustrated by way of experimental models of mechanical mesangial failure. Such failure may express itself as mesangial widening, increased transmesangial macromolecule "traffic," ballooning of capillary segments, and unfolding of capillary loops. Mechanisms are described by which these structural changes may lead to segmental glomerular sclerosis. PMID- 1450640 TI - Mesangial cells in the pathogenesis of progressive glomerular disease in animal models. AB - Increasing evidence supports a role for glomerular mesangial cell proliferation and over-production of extracellular matrix by mesangial cells in the development of focal or diffuse glomerulosclerosis. Experimental data obtained mainly in the chronic progressive remnant kidney model and in the acute mesangioproliferative anti-Thy 1.1 glomerulonephritis in rats have shed some insights into the factors governing mesangial cell proliferation and matrix synthesis in vivo. In these experimental models, mesangial cell activation can be demonstrated early in the course of disease as exemplified by the de novo expression by the mesangial cell of a smooth muscle "specific" actin isotype (i.e., alpha-smooth muscle actin). Following mesangial cell activation, cellular proliferation ensues both in the acute anti-Thy 1.1 model and, to a lesser degree, in the chronic remnant kidney model. While a multitude of mitogens for mesangial cells has been proposed on the basis of in vitro experiments, the factors involved in the regulation of mesangial cell proliferation in vivo remain largely undefined. Three growth factors which may have important roles in the in vivo mesangioproliferative response are platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta). All three cytokine growth factors are present in various inflammatory cells as well as in mesangial cells themselves, thereby allowing these factors to mediate cell proliferation by either paracrine and/or autocrine pathways. In vivo studies show that PDGF, bFGF, and TGF-beta participate in the mesangial cell proliferation and/or the mesangial matrix expansion that follows mesangial cell injury with anti-Thy 1.1 antibody.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450642 TI - A review of nursing strategies to reduce patient anxiety in coronary care. Part 2. AB - Illness and associated hospitalisation are stressful events for any individual. The stress associated with an admission to a coronary care unit may be related to the severity and acuteness of the illness, the effects of hospitalisation on the individual, their family, their job and financial position, and often manifests itself as anxiety, fear or depression. This paper highlights the use of anxiety reduction strategies such as muscle relaxation, music, education and counseling. The literature reviewed does not provide any clear messages regarding the effectiveness of these strategies in the coronary care unit setting. As a consequence, there is a need to continue researching this important area of nursing practice. PMID- 1450641 TI - Pathology of the human mesangium in situ. AB - Mesangial cells play an important role in the development and progression of human glomerular disease. This article summarizes some important aspects of mesangial properties and behaviour in situ. Intrinsic mesangial cells express alpha-smooth muscle actin and are best characterized as myofibroblasts or glomerular pericytes. The main integrin receptor in the mesangium is the alpha 1 beta 1 integrin. The beta 2 and beta 3 integrins have not been detected. Mesangial cells in situ fail to react with many monoclonal antibodies which stain human mesangial cells in culture, including leukocyte activation antigens. Prominent reactions in glomerular disease are mesangial expansion and progressive glomerular sclerosis, which are preceded by or associated with mesangial cell hypertrophy and/or proliferation. Mesangial enlargement is accompanied by an altered integrin expression and an abnormal composition of extracellular mesangial matrix. From the numerous autocrine and paracrine mediators identified in vitro which stimulate or inhibit mesangial cell growth and extracellular matrix synthesis, up to now only a few factors have been shown to be present in selected human glomerulopathies. These include platelet derived growth factors and platelet derived growth factor receptor beta, transforming growth factors beta, interleukin 1 beta, tumor necrosis factor alpha, and interleukin 6. Further identification of such mediators in situ will improve our understanding of pathological glomerular processes, particularly with respect to the multifunctional properties of the mesangial cell. PMID- 1450643 TI - Cerebral aneurysms and subarachnoid haemorrhage. AB - Up to 2000 Australians each year rupture a cerebral aneurysm. This is immediately fatal in some, and others remain disabled. The main risks after a first haemorrhage are recurrent bleeding, prevented by early surgery, and delayed cerebral ischaemia due to vasospasm. This is minimised by keeping a good fluid balance, calcium antagonists, and possibly newer treatments such as aminosteroids or plasminogen activator. An important problem is that of the missed haemorrhage, which often leads to delay in treatment and a fatal or disabling recurrence. PMID- 1450644 TI - Critical care nursing is a relatively new nursing specialty, but its membership is continuing to grow. PMID- 1450645 TI - A national communications campaign to disseminate information about the Disability Reform Package. PMID- 1450646 TI - Specialisation and developing standards within the national standards framework. PMID- 1450647 TI - Emergency nurse. Look to the future. PMID- 1450648 TI - Emergency nurse profile. Preparing for war--ready for disaster. Interview by Brian Dolan. PMID- 1450649 TI - Emergency nurse. Value for money reports. A & E departments: value for money? PMID- 1450650 TI - RITA--Registry of Industrial Toxicology Animal-data--progress of the working group. AB - A data base for the collection of histopathological diagnoses of neoplastic and pre-neoplastic lesions and related data from control animals involved in long term carcinogenicity or toxicity studies has been operated since 1988. Factors which may have an influence on the spontaneous tumor rate are integrated in the data base. Systematized nomenclature and standardized diagnostic criteria have been established as well as the applied data acquisition and data validation procedure. PMID- 1450651 TI - Ultrastructure and biochemistry of ischemic damages of small intestinal epithelial cells. AB - Ischemia (one hour) and following reperfusion (up to one hour) of the small intestine induce biochemical changes which are indices for the formation and action of oxygen free radicals and which occur predominantly during the reperfusion period. But the villi and the epithelial cells show different patterns of damage, occurring both at the end of the ischemic period and during the reperfusion period. Although the quantitative morphological changes are increased during the reperfusion in comparison with the ischemic phase the quality of the pattern of structural damage is the same in both periods of the experiment. This pattern of the damage includes: 1. the neighbourhood of groups of villi with total ischemic-lytic dissolution of the villi, of villi with damage of the epithelial cells at the tip and at the lateral area and of normal villi; 2. the different degree of structural damage of neighbouring epithelial cells within one villus whose cells are either of regular structural or damaged at subcellular organelles including the plasma membrane or of those being necrotically destroyed and on the way of release into the luminal space; 3. a differentiation of the structural changes of the microvilli and other organelles within single and neighbouring epithelial cells. The biochemical findings on purine nucleotide metabolism and on the formation of oxygen free radicals as "mean values" of a homogenate from a large group of cells cannot reflect the morphological-ultrastructural changes of single villi or even single epithelial cells. The possible reasons for the mosaicism of the morphological changes during ischemia and reperfusion are discussed. PMID- 1450652 TI - A new simulation approach for the determination of the error of parameters of biological importance describing the growth of the Ehrlich ascites tumor of the mouse. AB - Some aspects of the growth of the Ehrlich ascites tumor of the mouse can be described by the logistic function. The parameters used are fitted to the experimental data in a nonlinear way. It is important to determine the error of these parameters of biological importance in order to discriminate between different consequences induced by various experimental situations by means of statistics. But often there is a gap between the data that are available and the stronger assumptions necessary for statistics. We propose a simulation approach which also works in a much larger range of similar situations to close this gap. PMID- 1450653 TI - The influence of systemic hypoxia and reoxygenation on the glutathione redox system of brain, liver, lung and plasma in newborn rats. AB - The concentrations of reduced (GSH) and oxidized glutathione (glutathione disulfide, GSSG) in lung, liver, brain and plasma of newborn rats were investigated under the condition of reversible hypoxia. Brain and lung of newborn rats seem to be susceptible to reversible hypoxia. We found an increase in GSSG concentration after hypoxia in these organs. This alteration of the GSH-GSSG redox system was reversible within 2 hours of reoxygenation. A second increase in cerebral GSSG concentration after 4 hours of reoxygenation was connected with fasting during the experiment. In the liver we found a hypoxia dependent decrease in the GSH level, followed by a decrease in GSSG concentration. The increased GSSG concentrations in lung and brain are accompanied by an enhancement of plasma GSSG concentration. PMID- 1450654 TI - Bile salt-associated electrolyte secretion. A study following a short-term biliary obstruction in the rat. AB - The mechanisms involved in bile salt-induced choleresis are poorly known. To give an insight in this physiological process, bile salt-associated electrolyte secretion was studied following relief of a short-term (2h) biliary obstruction in the rat, an experimental model that shows an important diminution of bile salt choleretic efficiency. For this purpose, biliary excretion of total bile salts and electrolytes (sodium, chloride and bicarbonate) were studied in such a model during taurocholate infusion at increasing rates. The results showed that bile flow, bile salt output and electrolyte secretion stimulated by taurocholate administration were decreased in the rats that were subjected to biliary obstruction. Besides, the choleretic efficiency of the excreted bile salts, as estimated by the slope of the regression line of bile flow vs. bile salt output, was diminished by 46% (p < 0.005). Multiple regression analysis of bile flow vs. bile salt and electrolyte outputs allowed to detect a selective diminution of the fraction of bile flow related to bile salt-associated electrolyte secretion ("secretory fraction" of the choleretic efficiency of bile salts) (3.2 +/- 0.3 vs. 2.5 +/- 0.2 L/mol, p < 0.05) whereas the "osmotic fraction" of the choleretic efficiency of bile salts was not modified by the treatment (5.0 +/- 0.4 vs. 5.1 +/- 0.3 L/mol, p > 0.05). Since both chloride and bicarbonate biliary concentrations in the volume of bile stimulated by taurocholate were reduced by 53% and 52% respectively, a role of these anions in the generation of bile salt induced choleresis was suggested. Possible mechanisms involved in such a process and in its early impairment during cholestasis are discussed. PMID- 1450655 TI - Laser treatment of diffuse retinal pigment epitheliopathy. AB - The Authors report laser treatment of 18 eyes (14 patients) with a variant of central serous chorioretinopathy associated with widespread decompensation of the retinal pigment epithelium (RPE) in the macula, diffuse retinal pigment epitheliopathy (DRPE). All eighteen eyes with DRPE were treated with Krypton red laser photocoagulation in a grid pattern to leaking RPE in areas of neurosensory retinal detachment. All eyes showed anatomic improvement with resolution of the serous macular detachment and lipid exudation. The visual acuity was stabilized in 15 eyes (83%) at 6 months' follow-up, but only 3 eyes (17%) demonstrated improved visual acuity in the same time interval. At eighteen months, 2 of 15 eyes (13%) retained improved visual acuity, 11 eyes (74%) remained unchanged, and 2 eyes (13%) had visual loss. In this series of patients with DRPE, grid laser photocoagulation treatment was uniformly successful in producing an anatomic improvement in the exudative manifestations of the macula and in preventing or slowing progression of vision loss. PMID- 1450656 TI - Surgical management of exudative maculopathies: preliminary report. AB - A new surgical approach to the management of exudative maculopathies has been developed including the transvitreal route. As a result of surgery the subretinal spaces are drained and their viscous content removed. A special tool was designed for this operation. The method has been clinically tested on 32 patients (32 eyes) with different forms of age-related macular degeneration in the phase of complicated pigment epithelium detachment and on six patients (six eyes) with myopic exudative maculopathy. The follow-up ranged from 6 to 32 months. No fluid reappeared in the macular zone in patients with age-related macular degeneration, except one; visual function improved in 26 out of 32 cases (81.3%). Similar results were obtained in all six patients with myopic exudative maculopathy. PMID- 1450657 TI - Ophthalmic aid to eastern Europe: can the individual ophthalmologist help? AB - The problems of ophthalmic care in the newly independent countries of Central and Eastern Europe may not be fully appreciated by Western ophthalmologists. Information that has been received as a result of a questionnaire is discussed and some suggestions are made by which help can be given to countries that have been disadvantaged by political and economic influences for nearly half a century. PMID- 1450658 TI - Fundus angiography with fluorescein-labelled peptide fraction from bovine factor VIII: correlation with histologic findings. AB - A peptide fraction (VUEFFE) obtained from bovine factor VIII, with a high affinity for vessel endothelium, was bound to fluorescein and used for angiography in rabbits. Several eyes had undergone laser photocoagulation on the retina. The location of the dye was studied histologically with fluorescence microscopy on the enucleated, freeze-dried eyes. The angiographic and histologic findings were compared with findings obtained using sodium fluorescein. Fluorescein-labelled VUEFFE gave a longer lasting fluorescence of the retinal vessels with histologic evidence of dye deposition on the vessel wall. It also showed marked affinity for the photocoagulated tissues, giving intense and prolonged staining of the laser burns. Possible clinical applications are discussed. PMID- 1450659 TI - Randomised double-masked trial of lodoxamide and sodium cromoglycate in allergic eye disease. A multicentre study. AB - 135 patients were entered into a 28-day randomized double-masked multicentre study comparing the efficacy and short-term safety of lodoxamide 0.1% ophthalmic solution (Alomide--Alcon Laboratories), a mast cell stabilizer, with sodium cromoglycate 2% ophthalmic solution (Opticrom--Fisons Pharmaceuticals) in the treatment of allergic eye disease. Patients given lodoxamide 0.1% showed a significantly more rapid and greater improvement in their signs and symptoms of allergic eye disease than patients given sodium cromoglycate 2%. Both treatments were found to be safe, and side-effect profiles were comparable between the two treatment groups, although the overall incidence of side-effects in this study was found to be less frequent in the lodoxamide-treated group. PMID- 1450660 TI - Metastatic or dystrophic conjunctival calcification in renal failure? AB - In renal failure the incidence of pingueculae is significantly higher than in a comparable control group but there is no evidence that the calcific precipitation in renal failure is of a dystrophic nature. The lime salts are not located within the area of elastotic degeneration, a prerequisite for dystrophic degeneration. Moreover there is no association between the magnitude of the conjunctival degeneration and the degree of calcification. This makes it likely that the calcium precipitates represent metastatic calcification even though admittedly support for this assumption is tenuous. PMID- 1450661 TI - Multifunctional DNA-binding proteins in yeast. PMID- 1450662 TI - Sequences within the R region of the long terminal repeat activate basal transcription from the HIV-1 promoter. AB - The importance of the R region in basal human immunodeficiency virus type 1 (HIV 1) transcription was addressed by comparing a panel of HIV-1 R region mutants using in vitro and in vivo assays. Using deletion, base substitution mutants, and compensatory mutants, the precise R region sequences essential for basal HIV-1 promoter activity in vitro were mapped to sequences between +17 to +21. Within this regulatory domain, nucleotides +19 and +21 appear to be critical. The effect of these mutations on steady state RNA levels in transfected cells has been analyzed by S1 nuclease protection assay using uniformly labeled probes. Two main conclusions may be drawn from these studies. First, HIV-1 basal transcription is abundant, with the majority of correctly initiated transcripts truncated between sequences +57 to +70. Second, analysis of the compensatory mutants indicates the secondary structure of the nascent R region RNA is not an obligate requirement for the production of the truncated transcripts. Mutations in R region primary sequence that selectively abolish the production of the truncated transcripts in vivo also exhibit reduced promoter activity in vitro. The appearance of high levels of truncated transcripts raise the interesting possibility that-similar to c-myc, c-myb, and c-fos--basal HIV-1 expression is regulated by transcription elongation. PMID- 1450663 TI - Members of the USF family of helix-loop-helix proteins bind DNA as homo- as well as heterodimers. AB - We have isolated human cDNA clones for USF2, a new member of the upstream stimulatory factor (USF) family of transcription factors. Analysis of these clones revealed the existence of highly conserved elements in the C terminal region of all USF proteins. These include the basic region, helix-loop-helix (HLH) motif, and, in the case of the human proteins, the C-terminal leucine repeat (LR). In addition, a highly conserved USF-specific domain is located immediately upstream of the basic region. Using in vitro translated proteins, we found that all members of the USF family bound DNA as dimers. The N-terminal portion of USF, including the USF-specific domain, was entirely dispensable for dimer formation and DNA-binding. However, deletion mutants of USF2 lacking the LR were deficient in DNA-binding activity. Interestingly, each of the USF proteins could form functional heterodimers with the other family members, including the sea urchin USF, which does not have a LR motif. This indicates that the conserved LR in human USF is not required for dimer formation, and influences only indirectly DNA-binding. PMID- 1450664 TI - Regulation of E2F/cyclin A-containing complex upon retinoic acid-induced differentiation of teratocarcinoma cells. AB - Retinoic acid-induced differentiation of mouse P19 teratocarcinoma cells is accompanied by alterations in the level of E2F transcription factor. P19 stem cells contain free, uncomplexed E2F and an E2F complex termed E2F/stem. This stem cell complex is a heterotrimeric protein aggregate consisting of E2F transcription factor, E2F-binding protein (E2F/bp1), and cyclin A. Retinoic acid treatment converts P19 stem cells into differentiated neurons, glial cells, and fibroblasts. The presented experiments clearly show that the level of uncomplexed E2F gradually decreases upon differentiation, and fully differentiated cells do not contain free E2F. In addition, the stem cell-specific E2F aggregate is converted into a smaller complex, termed E2F/diff. This smaller complex, which is specific for differentiated cells, does not contain cyclin A and consists of E2F transcription factor associated with E2F/bp1. Finally, the role of E2F complexes in the cessation of cell proliferation, which accompanies P19 cell differentiation, is discussed. PMID- 1450665 TI - Differential modes of activation define orphan subclasses within the steroid/thyroid receptor superfamily. AB - We report that three orphan receptors, hERR1, hERR2, and hTR2, members of the steroid/thyroid receptor (SR/TR) superfamily, can be activated by different ligand-independent pathways. hERR1 and hERR2 exhibit constitutive activity in the absence of exogenously added ligands. Furthermore, this constitutive activity is localized in the carboxy terminal domain of both receptors and can be transferred to other members of this superfamily using domain switch strategies. In addition, we show that hERR1 can remain constitutively active in the less evolved eukaryotic cell Saccharomyces cerevisiae. In contrast, hTR2 is not constitutively active. However, a chimera of hTR2 can be activated in a ligand-independent manner through a signal transduction pathway initiated at the cell membrane by the neurotransmitter dopamine. Like hERR1 and hERR2, hTR2 is ligand-independently activated through its carboxy terminal domain. Together, these results suggest the existence of emerging subgroups within the SR/TR superfamily that can regulate gene expression through different modes of activation. PMID- 1450666 TI - Mutation analysis of the Cys-X2-Cys-X19-Cys-X2-Cys motif in the beta subunit of eukaryotic translation initiation factor 2. AB - Recessive lethal mutations in the beta subunit of eIF-2 that restore HIS4 expression in the absence of an AUG start codon were isolated from diploid Saccharomyces cerevisiae strains. DNA sequence analysis of these alleles and of eIF-2 beta suppressor alleles isolated from haploid strains, identified point mutations that altered one of six amino acids that map to a Cys-X2-Cys-X19-Cys-X2 Cys "zinc finger" motif and immediately adjacent residues. Five of the affected amino acids are identical in the human and yeast eIF-2 beta protein. Together with earlier studies (Donahue et al., 1988), these point mutations implicate the zinc finger domain of eIF-2 beta in start-site selection during the scanning process. We have supplemented the mutations obtained by genetic selection with an additional set of constructed mutations in this region. Our studies indicate that the cysteine residues and the intervening amino acids of this motif are essential for eIF-2 beta function in translation initiation in vivo. However, the effects observed in cells containing a copy of eIF-2 beta with a deletion of this motif suggest that this mutated form is still able to associate with other components of the initiation complex, imparting defects on translation initiation. Thus, this motif may be required only for later events that lead to initiator codon recognition. Alterations in defined positions, as found in our suppressor alleles, could lead to recognition of non-AUG codons. PMID- 1450667 TI - Fotemustine: an overview of its clinical activity in disseminated malignant melanoma. AB - Fotemustine is a new chloronitrosourea which is active against disseminated malignant melanoma (DMM), and especially against cerebral metastases (CM). This efficacy has been widely demonstrated through many phase II studies. A multicentre trial of monotherapy was undertaken in 153 evaluable French patients. A response rate (RR) of 24.2% (25.0% RR in CM; 31.8% in non-visceral metastases (NVM) was obtained. Three other phase II studies confirmed these results with respective objective RR of 16.7%, 20.0% and 47.0% and RR in CM of 8.3%, 14.3% and 60.0%. Fotemustine has also been used in combination with dacarbazine (DTIC), in patients with DMM. The RR among 103 patients was 27.2% (26.3% in CM, 37.5% in NVM), confirming the activity of fotemustine. The two drugs have also been administered sequentially, in order to exploit their synergism in interfering with the O6 alkyltransferase. Impressive RR have been achieved, especially in patients with visceral metastases (VM) but at the expense of a pulmonary toxicity that does not arise with other treatment schedules and which precludes its use outside of strictly conducted clinical trials. PMID- 1450668 TI - Tamoxifen as a single agent for advanced melanoma in postmenopausal women. A phase II study of the EORTC Malignant Melanoma Cooperative Group. AB - Between 1983 and 1989 a phase II study was carried out by the EORTC Malignant Melanoma Cooperative Group in which postmenopausal women with advanced melanoma but a good performance status received tamoxifen, 40 mg per day, as a single agent. From 12 centres, 114 patients were registered of whom 107 appeared to be eligible and 102 evaluable. Seven died of progressive disease within 4 weeks, eight others had early progressive disease (of whom seven died within 7 weeks). The response rate was 4.9%, the complete response rate 1%. Without prior chemotherapy three of 58 responded, with prior chemotherapy two of 44. Except for one of 46 patients with lung metastases who experienced a PR of these metastases, all responders were patients with slowly growing small soft tissue metastases. We conclude that, because of the few side effects, tamoxifen can be recommended for (postmenopausal) patients who have only a small number of slowly growing metastases and who are not yet candidates for treatment with toxic drugs. PMID- 1450669 TI - BANS: a discussion of the problem. AB - The significance of the BANS location (upper Back, posterior Arm, Neck and Scalp) as a prognostic factor in patients with stage I melanoma is controversial. A meta analysis performed by Weinstock et al. on their own and five comparable studies corroborated the hypothesis that this location is influential in the prognosis of intermediate thickness (0.76-1.69 mm) melanomas. Our study investigated the relationship between BANS subsites, thickness and prognosis in 1,082 stage I melanoma patients from two major Italian centres, Turin and Florence. A BANS primary was observed in 212 (19.5%) patients: recurrences occurred in 85 of them (40.1%) vs 309/870 non-BANS patients (35.5%). Overall survival probabilities were significantly shorter (p less than 0.01) in the BANS group (69.1% vs 76.7% at 5 years; 59% vs 68.5% at 10 years). The prognostic value of the BANS location was confirmed by a multivariate analysis using the Cox proportional hazards model. Stratification of BANS and non-BANS groups by thickness clusters showed a significant difference in both survival (p less than 0.001) and disease-free interval (p less than 0.05) in the 3.01-4.00 mm thickness subset, due to the greater incidence of distant and visceral metastases. In the 0.76-1.69 mm thickness range the significance was p = 0.06. PMID- 1450670 TI - Results obtained by using a computerized image analysis system designed as an aid to diagnosis of cutaneous melanoma. AB - Results obtained using a computerized image analysis system as an aid to clinical diagnosis of melanoma are reported. The system comprises a colour television camera connected through a digitizing board to a 386 personal computer. By means of original algorithms able to measure the shape, the colours and texture of a pigmented lesion of the skin, the system provides eight on/off indicators that are matched with the histological diagnosis to identify benign and malignant pigmented lesions. The chances that a given lesion is malignant increase with the increasing number of positive indicators. The training field of the system was constituted of images and data of 169 cutaneous lesions in 165 patients. Taking two positive indicators as the threshold between pigmented benign and malignant lesions, the efficiency of the system is 0.98, the positive predictive value is 0.45 and the negative predictive value is 0.95. These values were confirmed in a series of 44 pigmented lesions, 10 of which were melanoma, that constitute the present test series. The authors conclude that this computerized image analysis system should be regarded as a useful aid to diagnosis for a non-expert clinician. The system limit is transformation within a naevus. PMID- 1450671 TI - A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumour tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-borono-2-[18F]fluoro-L-phenylalanine. AB - A unique in vivo approach to assessing the concentrations of 4-[10B]borono-L phenylalanine (L-BPA), a melanoma targeting compound for boron neutron capture therapy (BNCT), was investigated using L-BPA labelled with positron-emitting 18F (half-life = 110 min), i.e., 4-[10B]borono-2-[18F]fluoro-L-phenylalanine (L [18F]FBPA). High melanoma uptake of L-[18F]FBPA was reduced slightly by competition with L-BPA in the two animal models of the murine B16 melanoma and the melanotic Greene's melanoma No. 179 in hamsters. In mice given L-[18F]FBPA and L-BPA, the concentrations of 10B in B16 estimated from 18F radioactivity were lower than those measured by inductively coupled plasma-atomic emission spectroscopy. Lower estimated values were dependent on the time after injection and on the loading dose of L-BPA. The estimated 10B concentrations for Green's melanomas were comparable to the measured values. Positron emission tomography (PET) using L-[18F]FBPA allowed Greene's melanomas to be clearly visualized. In conclusion, when L-[18F]FBPA is used as a probe for L-BPA in BNCT of malignant melanomas, the melanoma can be localized and the 10B concentrations in tissues can be assessed in vivo using 18F radioactivity by PET. PMID- 1450672 TI - Expression of cytokine genes, including IL-6, in human malignant melanoma cell lines. AB - As a preliminary to transducing human melanoma cells with lymphokine genes, we sought for constitutive gene expression and production of eight interleukins, tumour necrosis factors and granulocyte-colony stimulating factor in 19 human melanoma cell lines. Conversion of RNA into cDNA by reverse transcriptase and polymerase chain reaction (RT-PCR) were employed to evaluate gene expression while enzyme-linked immunosorbent assays (ELISA) or biological assays were used to assess the presence of proteins. No expression of interleukins (IL) 3, 4, and 5 or interferon-gamma RNA was found, while the other cytokines were variably expressed in melanoma lines, with IL-1 alpha, IL-1 beta, IL-6, IL-8, being detectable in most of the lines. At protein level, 10 melanoma cells were tested with ELISA and all were found to produce IL-8, five produced IL-6, two tumour necrosis factor (TNF)-alpha, one IL-1 alpha and two TNF beta. The levels of TNF beta were at the limit of test sensitivity. The amount of various cytokines released by the different lines varied widely. Biological assay with the D10-G4 clone confirmed the presence of IL-1 alpha in the supernatant of melanoma (ME) 10221 and revealed an IL-1 activity in the supernatant of Me 4024/1. The proliferating activity of melanoma supernatants on D10-G4 was inhibited by treatment with polyclonal antibodies against IL-1 alpha but not with antibodies against IL-1 beta. TNF biological activity was tested against the TNF-susceptible fibrosarcoma WEHI 164 clone 13.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450673 TI - High sensitivity of human melanoma cell lines to the growth inhibitory activity of mycoplasmal arginine deiminase in vitro. AB - Arginine deiminase (AD) is a potent growth inhibitor for some but not all tumour cell lines in vitro. As AD catalyses the direct conversion of L-arginine to L citrulline, the AD-sensitivity of various tumour cells might be attributed to the levels of urea cycle enzymes involved in L-arginine biosynthesis. This study demonstrated that human melanoma cells were highly sensitive to the growth inhibitory activity of AD. Five melanoma cell lines tested also exhibited reduced argininosuccinate synthetase (ASS) gene expression--being almost absent in four cell lines and at low level in one cell line. This resulted in an inability of the cells to utilize L-citrulline for growth. Based on the tissue-specific regulation of ASS gene, the feature of melanomas suggests that it might be possible to develop agents with strong AD activity for chemotherapeutic use for human melanomas in vivo. PMID- 1450674 TI - Febrile infections and malignant melanoma: results of a case-control study. AB - Several reports have described an inverse relationship between the frequency of infections and various malignancies. In this paper results of a hospital-based case control study on 139 melanoma patients and 271 suitable selected controls are presented, addressing the question of whether this relationship exists with respect to malignant melanoma while simultaneously controlling for the effects of other risk factors. Data on childhood diseases (group I), febrile diseases of adulthood (group II) and common febrile infections within a 5-year period prior to the diagnosis of melanoma (group III) were collected using a standardized interview. Group I diseases did not show a marked influence on the risk of malignant melanoma. Considering group II diseases, a significant protective effect was determined for chronic infectious diseases (OR = 0.32) and also for wound infections, abscesses and furunculosis (OR = 0.21). In group III, herpes simplex infections (OR = 0.45) and influenza/common cold (OR = 0.32) substantially reduced the melanoma risk. This effect was less pronounced for gastroenteritis (OR = 0.52). Analysis of the cumulative influence of infections pointed to a strong dose-response relationship between the frequency of febrile infections in adulthood and malignant melanoma. In particular, the risk reduction was striking when two or more febrile infections were compared to no febrile infections in group II (OR = 0.09) and group III (OR = 0.20). The study confirms the hypothesis that an inverse relationship exists between febrile infections and malignant melanoma, but these results have to be interpreted cautiously due to the inherent limitations of the case-control design.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450675 TI - Chronically evolving viral hepatitis. Meeting. Siena, Italy, 1990. PMID- 1450676 TI - Immune pathogenesis of hepatitis B. AB - Available information about the immune pathogenesis of HBV infection in man is very limited. However, the present availability of recombinant sources of the different HBV antigens expressed in the appropriate forms to induce activation of either HLA class I or HLA class II-restricted T cells, provides the necessary tools to investigate directly the mechanisms of liver damage, the role of the different cellular components of the immune system in HBV clearance and the specific nature of the immune defects potentially responsible for the chronic evolution of HBV infection. In addition, improved knowledge of HBV biology suggests a dynamic interpretation of the HBV-immune system interactions, based on which viral mutations as well as direct interferences of HBV with specific immune functions are believed to play a relevant role with respect to the outcome of HBV infection. PMID- 1450677 TI - PCR analysis of HBV infected sera: relationship between expression of pre-S antigens and viral replication. AB - In order to determine the biological significance of the pre-S antigens in HBV infection, HBsAg sera were tested for the presence of pre-S1 and pre-S2. HBV DNA was detected by spot-hybridization and PCR. The data show a complete correlation between pre-S antigenemia and HBV DNA replication in anti-HBe positive cases. PCR but not spot-hybridization was adequately sensitive to also detect HBV DNA in roughly half of the preS negative sera as well. Thus PCR appears to be a valuable technique for detection of potentially infectious anti-HBe carriers. PMID- 1450678 TI - Detection of HBV DNA by PCR in serum from an HBsAg negative blood donor implicated in cases of post-transfusion hepatitis B. AB - An HBsAg negative blood donor, and three of her recipients, who developed HBsAg positive post-transfusion hepatitis B, were all positive for serum HBV DNA by polymerase chain reaction (PCR), and by subtype discriminating PCR were found to harbour HBV specifying ayw. Thus HBV specifying ayw. Thus HBV DNA may be detected and sub-typed by PCR in infectious HBsAg negative individuals. PMID- 1450679 TI - Measurement of anti-HBc IgM levels using the Amerlite anti-HBc IgM assay. AB - The Amerlite anti-HBc IgM assay was evaluated as a tool for determination of antibody levels. With an assay time of 1 hour, the test showed a broad dose response range with high sensitivity and specificity. The software configuration of the analyser can be customized to suit specific research requirements. PMID- 1450680 TI - Evaluation of a new enhanced luminescence immunoassay for confirming the presence of HBsAg in human serum or plasma. AB - An enhanced luminescence assay was developed to confirm the presence of HBsAg in weakly reactive sera. The test proved reliable in differentiating between truly reactive and falsely reactive samples. PMID- 1450681 TI - Functions of hepatitis B surface proteins. AB - HBV surface proteins play a number of functional roles in cellular infection, viral synthesis and in immune responses of the host. Three coterminal proteins of differing sizes and three subdomains of the individual molecules can be recognized. In this brief review, functions of the various proteins and domains are described and their significance as potential immunogens is discussed. Although it is apparent that the surface proteins are involved in the development of persistent HBV infections, the underlying mechanisms of liver involvement remain unknown. PMID- 1450682 TI - Diverging policies for vaccination against hepatitis B. AB - Policies toward vaccination against hepatitis B vary globally according to local prevalence and the population of infected individuals. In the present report, vaccination plans, policies, risks, and experiences of both apparent successes and failures are described. Possible plans, including local vaccine production, are discussed in regard to problems of third-world countries with high HB prevalence. Recommendations are made for vaccination policies in various circumstances. PMID- 1450683 TI - Immunogenicity and safety of a recombinant hepatitis B vaccine produced in mammalian cells and containing the S and the preS2. AB - A group of 273 health care workers, at risk of HBV infection, underwent vaccination with recombinant HBsAg produced in mammalian cells and containing protein sequences coded by both the S and pre-S2 regions (Genhevac B). Preliminary results show that a very early pre-S2 response occurred which may be useful in post-exposure prophylaxis. This observation, in addition to reduced influence by the vaccination protocol, provides grounds for optimism in spite of the fact that the efficiency spectrum of this vaccine was not superior to that of recombinant vaccines produced in yeast. PMID- 1450684 TI - Kinetics of anti-HBs after hepatitis B vaccination: a comparison of two recombinant and one plasma-derived vaccines. AB - Geometric mean titers were determined for three groups of medical students who had been vaccinated against hepatitis B with two different yeast-derived recombinant vaccines and one plasma-derived vaccine. The antibody kinetics for the three groups were similar over a period of 4 years. A formula for prediction of titers from the post-booster anti-HBs concentration is provided. PMID- 1450685 TI - Enhanced luminescent assays for hepatitis markers: assessment of post vaccine responses. AB - A range of solid phase immunoassays have been developed using enhanced chemiluminescence to provide a signal which can be measured in a qualitative or quantitative manner. The "Amerlite" anti-HBs assay has been used routinely to test more than 3000 post-vaccine anti-HBs levels. The results show that 5% of vaccinees are non-responders, but that more than 30% produce antibody levels greater than 1000 mIU/ml. PMID- 1450686 TI - Hepatitis C viral RNA in serum of patients with chronic non-A, non-B hepatitis: detection by the polymerase chain reaction using multiple primer sets. AB - The recently introduced antibody test for hepatitis C virus (HCV) infection has proven to have certain limitations. Since HCV itself is usually present in clinical specimens at very low titers, a useful assay for the virus must have very high sensitivity. We have developed a simple, highly sensitive assay for HCV RNA based on the polymerase chain reaction (PCR). In this test, RNA extracted from HCV infected serum or plasma is used as the template for double PCR with nested primers. Sensitivity studies demonstrate that this assay is able to detect HCV at or beyond the sensitivity level of chimpanzee infectivity. We tested, with several sets of nested primers, 40 patients with chronic non-A, non-B hepatitis (36 seropositive and 4 seronegative) and found that 35/40 were PCR positive including all 4 seronegative patients. Normal human plasma and plasma from hepatitis B infected patients did not react in this test. This assay has proven to be valuable for determining the presence of HCV in various samples; furthermore, it offers the possibility of diagnosis of HCV infection in seronegative patients. PMID- 1450687 TI - Sequence analysis of PCR amplified hepatitis C virus cDNA from French non-A, non B hepatitis patients. PMID- 1450688 TI - T cell recognition of hepatitis B envelope proteins. AB - We have studied the T-cell processing pathways of Hepatitis B antigens and the role of specific B lymphocytes. It could be shown that some form of processing by specific B cells is required for class I CTLs. This mechanism differs from class II endosomal processing. In addition, it could be shown that lysis of HBsAg specific B cells may be partly responsible for chronic HBV carrier states. PMID- 1450689 TI - HCV infection and chronic active hepatitis in alcoholics. AB - Histological signs of chronic active hepatitis were found in 11/41 (27%) patients with chronic alcoholic liver disease. All these 11 patients tested positive for antibodies to HCV and no other causes of chronic hepatitis were found. PMID- 1450690 TI - Diagnostic reagents for hepatitis C virus. AB - The development of diagnostic methods for hepatitis C virus is presented. Special attention is paid to the selection of antigenic markers, the type of assay selected and the interpretation of results. A few of the pitfalls and ambiguities of various assays are discussed and possible future methods are described. PMID- 1450691 TI - Follow-up of patients with hepatitis non-A, non-B: incidence and persistence of anti-HCV depend on route of transmission. AB - Of 32 patients with non-A, non-B hepatitis, 10 (31%) were still anti-HCV-positive 12.8 years after the acute phase of the disease. Seven of the patients (21.9%) still had elevated ALT levels, and among these, 5 out of 5 patients who had been subject to parenteral risk were anti-HCV-positive. In contrast, none of the patients who had not been subject to parenteral risks were positive. PMID- 1450692 TI - Recombinant immunoblot assay for hepatitis C virus antibody in chronic hepatitis. AB - Testing for hepatitis C virus by ELISA requires confirmation by recombinant immunoblot assay (RIBA). The first-generation RIBA uses the same antigen as used in the ELISA and one further antigen. A second-generation RIBA in which two further antigens are present, detects positivity that is not found by either the ELISA or the original RIBA. Consequently, although it is adequate to test ELISA positive sera with the first-generation RIBA, the second-generation assay is recommended for confirming negativity. PMID- 1450693 TI - PCR detection of HCV RNA among French non-A, non-B hepatitis patients. AB - Hepatitis C virus (HCV) cDNA was amplified from serum of 26/40 French chronic non A, non-B hepatitis patients by the nested polymerase chain reaction. Compared with anti-C100, viral cDNA represents a more reliable marker of active HCV replication. PMID- 1450694 TI - Evaluation of anti-HCV positive blood donors identified during routine screening. AB - Of 30,231 donors tested, 368 (1.2%) were anti-HCV positive. Of these, 254 have been evaluated, with the following results: only 25% have a history of parenteral risk, seroprevalence increases with age and approximately 80% of those that are anti-HCV positive in our population are probably infected with HCV. In addition, an unexpectedly large number of these persons have chronic and/or severe liver disease and will require combined diagnostic approaches for accurate evaluation. PMID- 1450695 TI - Presence of HCV RNA in serum of asymptomatic blood donors involved in post transfusion hepatitis (PTH). AB - To study the causes of residual posttransfusion hepatitis, serum from implicated donors was tested by PCR for the presence of HCV RNA. Of 20 anti HCV negative donors, 4 were HCV RNA positive and thus, infective. The results suggest that higher-level investigations are necessary for prospective donors who present blood enzyme abnormalities or other questionable characteristics. PMID- 1450696 TI - Epidemiology of anti-HCV antibodies in France. Viral Hepatitis Study Group of the French Blood Transfusion Society. AB - The aim of this large survey which covered 173,038 unselected blood donors, was to determine the seroprevalence of anti-HCV antibodies and surrogate markers (ALT and anti-HBc) in France. The results revealed a frequency of 0.63% of anti-HCV positive donors. The correlation with surrogate markers was very poor but since we know nothing about the infectivity of anti-HCV negative donations, screening of surrogate markers must still be performed to prevent post-transfusional hepatitis. PMID- 1450697 TI - Assay of antibodies to hepatitis C virus protein C100-3 in blood donors from northern Germany. AB - The prevalence of anti-C100-3 increases with age from 0.41% to 1.26%. It is more frequent in donors with elevated ALT (4.5%). Most ALT elevations, however, are not related to anti-C100-3. Low EIA signals (< 3 x cutoff) are often non specific. The cutoff value should be 2.5 times higher. High EIA signals correlate with ALT elevations. PMID- 1450698 TI - Chronic viral hepatitis in children. AB - Hepatitis B virus is the most common causative agent of chronic viral hepatitis in children. The disease may take an aggressive course, but remains mostly asymptomatic. HDV infection occurs in about 13% of those children who are chronic carriers and are HBsAg positive. HCV infection is generally related to parenteral risk and generally remains asymptomatic. In addition to describing the course of the various diseases, treatment and control measures are discussed. PMID- 1450699 TI - Long-term outcome of chronic type B hepatitis in childhood. AB - The course of hepatitis B was followed in 35 children. Various prognostic factors are evaluated. The long-term outcome of the disease is poor, often progressing to cirrhosis. PMID- 1450700 TI - Repeated course of interferon treatment in chronic hepatitis B in childhood. AB - Ten children affected by HBV chronic hepatitis, not responding to a previous treatment with interferon (IFN), have been treated with a reiterated IFN therapy. The response obtained is not encouraging and only one patient became negative for HBeAg and HBV-DNA. PMID- 1450701 TI - Effect of prednisone priming followed by alfa-interferon in treatment of children with chronic hepatitis B: an interim analysis of a controlled trial. AB - A six-month analysis of a controlled trial on the treatment of chronic hepatitis B in children shows that prednisone priming followed by alpha-interferon 2A was effective in 6 of 9 treated patients in reducing HBV replication and disease activity. PMID- 1450703 TI - Treatment of chronic viral hepatitis anno 1990. AB - The therapeutic efficacy of alpha-interferon therapy in chronic hepatitis is discussed in light of various international studies. Although beneficial to some extent, treatment is of limited value and is accompanied by more-or-less serious side effects. Development of complementary drugs and new therapeutic methods must therefore be continued. PMID- 1450702 TI - Association between HLA class I antigens and response to interferon therapy in children with chronic HBV hepatitis. AB - In this preliminary study, children with chronic HBV hepatitis, as was also previously shown for adults, respond to interferon therapy in an HLA class I antigen dependent manner. If this can be confirmed on a large scale, HLA typing may serve as a useful indication of interferon-therapy responders. PMID- 1450704 TI - HBcAg induced T-cell independent anti-HBc production in chronic HBsAg carriers. AB - The capacity of the nucleocapsid protein of HBV to function as a T-cell independent antigen in man was studied. When T-cell depleted B-cell cultures were challenged with E coli-derived HBcAg, anti-HBc production was registered in culture supernatants from the majority of chronic HBsAg carriers in a quiescent stage of disease. In contrast, similarly prepared and stimulated cultures from donors with natural acquired immunity to hepatitis B or HB-susceptible controls were non-responsive. Addition of autologous T-cells effectively restored anti-HBc responsiveness in T-cell depleted B-cell cultures from HB-immune donors, demonstrating the T-cell dependency for anti-HBc induction in natural HBV infection. PMID- 1450705 TI - Induction of autoantibodies during alpha interferon treatment in chronic hepatitis B. AB - Thirty-two patients with chronic hepatitis B treated with alpha interferon were tested for 12 different antibodies. Only a minority (18%) of cases developed antinuclear antibodies and none developed clinical signs of autoimmune disease. These data suggest that, at the dose regimen used, interferon therapy of chronic hepatitis B is not associated with triggering of autoimmunity. PMID- 1450706 TI - One course versus two courses of recombinant alpha interferon in chronic C hepatitis. AB - Fifty-five patients with antibodies to HCV and chronic liver disease have been enrolled in the study. Thirty-four patients were treated with recombinant alpha interferon (IFN, 3 MU daily for 10 days followed by 3 MU twice/week for 3 months), and were compared to 21 untreated controls. Alanine aminotransferase (ALT) normalization was observed in a significant proportion of treated patients (52.9%), but 66.6% of them experienced a relapse after discontinuation of the therapy. The evaluation of the early ALT behavior after the 10 days priming with daily IFN administration was useful in predicting the response. The administration of a second IFN course with the same schedule and duration as the first course did not increase the efficacy of the treatment. Increased dosage and/or prolonged administration are probably required. PMID- 1450707 TI - Interferon therapy of cryptogenic chronic active liver disease and its relationship to anti-HCV. AB - In a randomized controlled trial of Interferon (IFN) in 60 patients (30 treated and 30 controls) with cryptogenic chronic active liver disease, 70% of treated patients showed complete response, but a high rate of biochemical relapse (62%) was noted. In these cases, a second response to higher doses of IFN has been more difficult and less frequent. A response to IFN was found in 88.5% of anti-HCV positive treated patients and only in 25% of anti-HCV negative. We suggest that serum anti-HCV is a suitable test to predict the response to IFN. PMID- 1450708 TI - Immune pathogenesis of hepatitis A. AB - In an effort to elucidate the mechanism of liver damage resulting from Hepatitis A virus (HAV) infection, we have studied infected skin fibroblasts and autologous lymphocytes from HAV patients. We report here that HLA-restricted virus-specific T cells play an essential role in HAV-related hepatocellular injury. PMID- 1450709 TI - Interferon alpha 2-b therapy of HCV and nonBnonC chronic hepatitis. AB - Twenty-four patients with HCV and NonBNonC chronic hepatitis--4 with HIV coinfection--were treated with r-IFN alpha for at least six months. In this period 62.5% of patients show a normalization of ALT but not a sustained remission. Non-responders have histologically more severe and long-lasting chronic hepatitis. PMID- 1450710 TI - Long-term effects of recombinant leukocyte alpha interferon in the treatment of chronic delta hepatitis. AB - A pilot study is described, in which 25 chronic CDH patients were treated with 3 MU recombinant alpha-interferon per week for 4 months. Improvement was transient and no long-term effects were noted. Side effects were well tolerated and reversible so that longer treatment and higher dosages should be possible. PMID- 1450711 TI - Liver transplantation and hepatitis viruses. AB - Considerations regarding liver transplantation in viral-hepatitis-related acute liver failure and end-stage chronic liver disease are discussed. Parameters of prognosis and indications for transplantation are presented. Differences according to the causative agent are noted, in particular regarding the danger of reinfection. The role of immunoprophylaxis is addressed as is the question of additional antiviral (interferon) treatment. PMID- 1450712 TI - Antibody to hepatitis C virus in acute, self-limited, type B hepatitis. AB - Sera from 104 patients with self-limited, acute type B hepatitis were tested for the presence of anti-HCV antibodies. The results show that especially drug users with acute type B (and occasionally coinfected with type D) hepatitis commonly are infected with HCV. Furthermore, HCV infection may have preceded infection with the other agents and may be responsible for high ALT levels. PMID- 1450713 TI - HCV infection in HBsAg positive chronic liver disease. AB - The prevalence of anti-HCV antibodies was determined for a group of 68 patients with various forms of chronic liver disease. All patients that were anti-HCV positive but did not show signs of HBV replication had severe liver disease. We therefore suggest that HCV may be responsible for liver damage in HBsAg positive subjects when there are no evident signs of HBV replication. PMID- 1450714 TI - HBV and HCV infection in i.v. drug addicts; coinfection with HIV. AB - A group of 122 drug addict patients were studied to evaluate the incidence of HIV, HBV, HCV infections and of laboratory findings of hepatic damage. Our data show that hepatic damage is more frequent in patients affected by HBV-HCV coinfection than those with HBV or HCV infection alone and that HIV positivity supports HBV-HCV coinfection. PMID- 1450715 TI - HCV and HIV infection among intravenous drug abusers in eastern Sicily. AB - In a study of 175 intravenous drug addicts from Eastern Sicily, 58.3% were found to be anti-HCV positive. In this population, the presence of anti-HCV was independent of HIV infection, age, duration of drug use and the practice of needle sharing. This may indicate that HCV is more readily transmitted (or spread earlier in this population) among drug addicts than is HIV. PMID- 1450716 TI - Anti-hepatitis C antibody prevalence among intravenous drug addicts in the Catanzaro area. AB - A higher seroprevalence of anti-HCV antibodies (63.4%) was found in 41 intravenous drug addicts (IVDA) when compared to 220 controls (1.8%). Life style is an important risk factor for HCV transmission among IVDA. PMID- 1450717 TI - Hepatitis C virus (HCV) infection in the Piacenza dialysis center. AB - In a group of 110 dialysis patients, 21% had anti-HCV antibodies. Statistical differences were noted according to method and duration of dialysis as well as the presence of further risk factors. PMID- 1450718 TI - Preliminary investigation on intrafamilial spread of hepatitis C virus (HCV). AB - To determine the risk of cohabitant HCV infection, we investigated the sera of 101 family members of 53 anti-HCV antibody positive chronic liver disease patients. Altogether 14.8% of the cohabitants were also anti-HCV antibody positive, compared to a prevalence of 1.4% in the general population. These results suggest that hepatitis-C-virus may spread by person-to-person infection. PMID- 1450719 TI - Involved factors in the intrafamilial spread of hepatitis C virus. AB - To investigate the risk of non-parenteral HCV infection, sera from 302 relatives of 120 anti-HCV positive subjects were tested for the presence of anti-HCV antibodies. For the sake of comparison, sera from 17,000 blood donors were also assayed. The prevalence of HCV positivity was 4.3% in household contacts, compared to 0.78% in the donor population, indicating a significantly higher risk of infection for family members. Close personal contact may not be as critical a factor for infection as is duration of the disease. PMID- 1450720 TI - Divergent anti-HBc reactivities in HB-immune and chronic HBsAg carriers. AB - We have monitored titers of anti-HBc antibodies in sera from acutely HBV-infected and chronic HBsAg carriers. Our data show that there is a divergence in the specificity of the antibodies in these two populations. We also present preliminary results showing that serum from HB-immune carriers contain antibodies that are multispecific and display autoimmune characteristics, reacting with human serum albumin. PMID- 1450721 TI - Absence of free core antigen in anti-HBc negative viremic hepatitis B carriers. AB - Using enzyme immune assay and immune electron microscopy, we have examined the sera of immune-suppressed anti-HBc negative HBV-infected patients for the presence of HBcAg. Our results suggest that free HBV core particles are absent or present only in minute amounts in the blood of chronic carriers and that at the most, only minimal amounts of core antigen are found on the surface of the virus particles. PMID- 1450722 TI - Homing of T-lymphocytes in acute and chronic HBV positive inflammatory liver disease. PMID- 1450723 TI - Hepatitis B virus specific transcripts in peripheral blood mononuclear cells. AB - We report on the analysis of HBV transcription in peripheral blood mononuclear cells of chronically infected patients by polymerase chain reaction amplification. Our results suggest that in these cells gene expression occurs either as pregenomic or subgenomic transcripts. PMID- 1450724 TI - Relapsing hepatitis A in Saimiri monkeys experimentally reinfected with a wild type hepatitis A virus (HAV). AB - Saimiri monkeys were inoculated three times with hepatitis A virus and observed in a follow-up study for sixteen months. The monkeys developed recurrent hepatitis involving liver damage and cycles of HAV antigen shedding in stools. The relapses were presumably due to immune response effects. PMID- 1450725 TI - Detection of transcriptionally active hepatitis B virus DNA in peripheral mononuclear blood cells after infection during immunosuppressive chemotherapy using the polymerase chain reaction. AB - Using PCR we have studied mononuclear peripheral blood leucocytes (PMBLs) from HBV-infected immunosuppressed patients in order to detect the presence of HBV genomes. Our results indicate that non-transient PMBL infection is common in immunotolerant carriers. In addition, the presence of pregenomic mRNA sequences suggests that virus replication may take place in PMBLs, possibly implicating the latter as a source of virus after replication has ceased in the liver. PMID- 1450726 TI - The hepatitis B virus X protein transactivation of c-fos and c-myc proto oncogenes is mediated by multiple transcription factors. AB - We have constructed two expression vectors in order to study the action of the HBV 17 Kd X protein on the c-fos and c-myc promoters. The results show that the promoters contain multiple elements that respond to X protein, suggesting involvement of multiple transcription factors. The exact mechanism of the interaction remains elusive, but our data allow speculation about the factors that may be influenced. PMID- 1450727 TI - Trans-activation by hepatitis B virus X protein is mediated via a tumour promoter pathway. AB - We have studied the c-myc gene as a possible target of HBV X protein in liver carcinogenesis. Our results indicate that trans-activation by X protein occurs via PKC/AP1 signal transduction, suggesting a possible two-step mechanism in HBV related liver carcinogenesis. PMID- 1450728 TI - Truncated pre-S/S proteins transactivate multiple target sequences. AB - In order to investigate the transactivational function of HBV truncated preS/S proteins we have constructed two sets of plasmids and have tested their transactivational potential on the c-myc regulatory sequences and the TPA responsive element. We found that preS/S proteins only become transactivationally active when truncated at the carboxy terminal end. Furthermore, using immunofluorescence microscopy we determined that the proteins are located exclusively in the cytoplasm, apparently ruling out DNA binding and activation of factors in the nucleus. PMID- 1450729 TI - Variants of hepatitis B virus. AB - Variations in the course of disease caused by hepatitis B virus may often be attributed to genomic variants of the virus. It must be kept in mind, however, that other factors, i.e. immunocompetence of the host and new methods of detection such as PCR, may also result in apparently aberrant phenotypic expression. Examples of both situations are presented here and the need is stressed for combined virological, biochemical and clinical studies. PMID- 1450730 TI - Hepatitis B virus (HBV) genomic variations in chronic hepatitis. AB - Using PCR we have examined the sequence of the pre-C/C region of HBV from sera of anti-HBe positive, chronically HBV-infected patients. The large majority of sera tested contained a mixture of heterogeneous pre-C sequences with 1-3 non-randomly located point mutations. Some of the resultant variant viruses are incapable of synthesizing immunogenic proteins and may be involved in viral persistence in chronic carrier states. PMID- 1450731 TI - Lack of pre-C region mutation in woodchuck hepatitis virus from seroconverted woodchucks. AB - Woodchuck hepatitis virus, which shares a large degree of homology with human HBV, was examined for indications of mutational variants. No alteration in the pre-C region was found, but as in HBV, viral DNA could still be detected by PCR after seroconversion to anti-WHe. PMID- 1450732 TI - Potyvirus serology, sequences and biology. AB - Amino acid sequences of the cytoplasmic cylindrical inclusion protein (CIP), large nuclear inclusion protein (NIb), and coat protein (CP) of potyviruses were re-examined in light of reported serological relationships, and correlated with known and deduced biological functions. No obvious correlations were observed between either amino acid sequences or epitopes recognized by monoclonal antibodies and the natural host ranges of the potyviruses examined. Whereas the identified sequence motifs of the RNA helicase (CIP) and replicase (NIb) are predicted to be antigenic, most of the conserved sequences and epitopes in the CIP, NIb and CP were presumed to be maintained for structural rather than functional reasons. Three possible potyvirus clusters are proposed on the basis of the length and composition of the virion surface-exposed amino terminal extension of the CP; these clusters do not correlate with overall CP sequence homology, host range, or vectors, but are of potential evolutionary significance and hence of possible taxonomic value. PMID- 1450733 TI - Coat protein phylogeny and systematics of potyviruses. AB - The feasibility of applying molecular phylogenetic methods of analysis to aligned coat-protein sequences and other molecular data derived from coat proteins or genomic sequences of members of the proposed taxonomic family of Potyviridae, is discussed. We show that comparative sequence analysis of whole coat-protein sequences may be used reliably to differentiate between sequences of closely related strains, and to show groupings of more distantly related viruses; that coat proteins of putative Potyviridae cluster according to the proposed generic divisions, and, even if some are only very distantly related, the members of the family form a cluster distinct from coat proteins of other filamentous and rod shaped viruses. Taxonomic revisions based on perceived evolutionary relationships, and the lack of feasibility of erecting higher taxa for these viruses, are discussed. PMID- 1450734 TI - Application of genome sequence information in potyvirus taxonomy: an overview. AB - The application of protein and nucleic acid sequence analysis in evolutionary and phylogenetic studies is well established. Available sequence information for the 5' untranslated region of potyviruses including the fungus-transmitted barley yellow mosaic virus (BaYMV) RNA-1 suggests that a 12-nucleotide conserved sequence, the "potybox" is unique to this group. Various non-structural proteins of potyviruses share considerable "signature" sequence homology across a broad spectrum of unrelated viruses, which makes their value limited to "supergroup" or "superfamily" identity. However, in potyviruses, the coat-protein N-terminal sequences and 3' noncoding regions are variable among viruses, but similar among strains of the same virus. This suggests that these sequences may be an accurate marker of genetic relatedness. Until complete genome sequences from a large number of potyviruses become available and their value in systematics is tested, coat protein and 3' noncoding regions remain as the choice of taxonomic indicators. The reason being, that cloning and sequencing of the coat-protein gene and 3' noncoding regions are less complicated and time consuming and the sequences show significant differences among the virus species within the family Potyviridae. PMID- 1450735 TI - Importance of host ranges and other biological properties for the taxonomy of plant viruses. AB - With reference to the confusion regarding the value of biological properties for the taxonomy of plant viruses, following proposal is made. Distinction between viruses should be based on the nucleotide sequences of the genome, whereas that between strains should take also biological characteristics into account. PMID- 1450736 TI - Clustering Potyviridae species on the basis of four major traits. AB - Cluster analysis was used to examine taxonomic relationships among 31 potyviruses, using four categorical variables; genome segmentation, vector, inclusion bodies produced and host range. Analysis showed that regardless of weight given to genome segmentation, the fungus-transmitted viruses clustered in one group and the rest of the viruses in another at 60% level of similarity. It has been concluded that the creation of one family to include both the bymoviruses and potyviruses seems to be a reasonable compromise at the present time. PMID- 1450737 TI - Specific infectivity and host resistance have predicated potyviral and pathotype nomenclature but relate less to taxonomy. AB - The names of potyviruses and viral-strains have represented the occurrence of predominant pathotypes on predominant crop genotypes. Thus virus nomenclature, but not viral taxonomy, has been decisively influenced by plant-genotype susceptibility and indirectly by host genetic resistance. REsistance to infection (i.e., host range) continues to serve a practical role in differentiating recognized viruses. Plant genes that confer disease tolerance or viral resistance remain a principal means of viral pathotype differentiation, as well as a principal control measure against major viral pathogens. Degrees of genetic diversity among isolates of recognized viruses should not be underestimated, and any system of viral taxonomy should be prepared for flexibility at the species level. PMID- 1450739 TI - Potential for using transgenic plants as a tool for virus taxonomy. PMID- 1450738 TI - Sources of resistance to viruses in the Potyviridae. AB - Resistance to 56 viruses in the family Potyviridae in 334 plant species was tabulated. Studies conducted in the last 60 years have elucidated the genetics and usefulness of 135 resistance genes, but no reports on the heritability of other sources of resistance are available. In most of the plant species, resistance to species of Potyviridae was simply inherited, either dominantly (60 genes) or recessively (39 genes). In some cases resistance was conferred by two or more genes. Symbols have been assigned to 86 genes, of which very few are duplicate entities. Resistance genes can be useful in determining relationships among these viruses, as well as for their identification. The role of conventional breeding and biotechnology in transferring genes from one species to another is discussed. PMID- 1450740 TI - A potyvirus in nature: indistinct populations. AB - Potyviruses occur in nature as a variable population. A number of strains have been reported for many potyviruses. Two or more viruses have been separated from "one virus" isolate. Experimental isolation and/or transmission often results in atypical viral isolates. A virus may be considered as a fuzzy population. We should properly understand the range of variation in one virus. The range of variation as well as typical characteristics of a virus should be included in future descriptions. PMID- 1450741 TI - Potyvirus taxonomy: potyviruses that affect solanaceous crops. AB - Serology has been the main, or at least an important, tool for differentiating potyviruses that affect solanaceous crops. At present, analysis of the genome by hybridization techniques has supported the differentiation of viruses demonstrated by serology. Phylogenetic groupings, based on nucleic acid sequences, should be combined with serological detection to make the groupings more usable. PMID- 1450742 TI - Biological variants of tobacco etch virus that induce morphologically distinct nuclear inclusions. AB - The presence of distinctive nuclear inclusions has been used for many years as a diagnostic character for tobacco etch virus (TEV). Cytological examinations of isolates of TEV in both weeds and solanaceous crops from areas widely separated geographically have demonstrated the presence of a variety of nuclear inclusions that vary considerably in form. Such inclusions can, in many cases, be related to differences in symptom expression. It is suggested that distinctive nuclear inclusions may be used to select biological variants of TEV that may be useful in the study and manipulation of closely related "strains" of this potyvirus. PMID- 1450743 TI - Biological variability of potyviruses, an example: zucchini yellow mosaic virus. AB - Potyviruses present an important variability which may affect biological properties such as host range, symptomatology, virulence towards resistance genes, and transmissibility by vectors. A brief account of this potential is presented and illustrated by some aspects of the biological variability of zucchini yellow mosaic virus (ZYMV). PMID- 1450744 TI - Designation of potyvirus genera: a question of perspective and timing. AB - It may be premature to subdivide the Potyviridae into genera (Bymovirus, Potyvirus, Rymovirus) since definitive serological and vector interrelationships between them remain to be established. Monogenic proposals for classifying Potyviridae should also be viewed askance until their practical value in agricultural settings can be demonstrated. PMID- 1450745 TI - Fungal transmission of a potyvirus: uredospores of Puccinia sorghi transmit maize dwarf mosaic virus. AB - Maize dwarf mosaic virus (MDMV) and maize rust, Puccinia sorghi Schw., occur as natural infections on cultivated maize in South Africa. P. sorghi often occurs as a secondary late infection on maize plants which have already been infected with MDMV earlier in the season, either seed or aphid transmitted. When MDMV isolates from maize plants naturally infected by both virus and fungus were propagated by sap inoculation in plant growth rooms, residual uredospores in the sap gave rise to the development of uredia under conditions of high humidity. When uredospores developing on MDMV-B-infected plants were germinated on virus free maize seedlings, these plants became infected with MDMV-B. Similarly, when uredospores, originating from maize plants infected with MDMV-A, were scattered onto virus free maize seedlings, these plants became infected with MDMV-A. The presence of virus on uredospores in infected plant tissue was visualized by indirect immunofluorescence. Identification of virus infection was by DAS-ELISA and immunoelectro-blotting utilizing strain-specific antisera. Virus transmission occurred between closely situated plants which had no actual contact (unaided transmission). MDMV-B transmission by uredospores, to new maize seedlings, has been maintained for three successive years (1988-1991) in a plant growth room. The MDMV-B isolate remained sap and non-persistently aphid transmissible. PMID- 1450746 TI - Inclusion bodies. AB - All viruses in the family Potyviridae which have been studied cytologically (currently 111) induce cylindrical inclusions in host cytoplasm. These inclusions are controlled by portions of the virus genome, therefore, viruses which induce them are related. Viruses in other groups do not induce this type of inclusion. Cylindrical inclusions have come to be recognized as one of the main characteristics of the family Potyviridae. They are used in diagnosis of diseases induced by these viruses. For diagnostic purposes the family can be separated into four subdivisions on the basis of differences in cylindrical inclusion morphologies. Assigning viruses to subdivisions assists in virus identification at the specific and in some instances at the strain level. PMID- 1450747 TI - The usefulness of aphid transmission as a taxonomic criterion for potyviruses. AB - In the past vector relationships have been one of the criteria used for delineating plant virus taxa. The proposed family, the Potyviridae, continues that practice. Aphid transmission of viruses within the genus Potyvirus is a useful characteristic in terms of identification, but is of only limited use in terms of taxonomy. This conclusion is based on a greater understanding of the molecular biology of potyviruses. The molecular basis of aphid transmission is not well understood at the present, but these data suggest that, beyond disease diagnosis, virus identification and characterization, and potential identification of genome microheterogeneity, aphid transmission should only be considered as a minor taxonomic criterion. PMID- 1450748 TI - Viruses of the Potyviridae with non-aphid vectors. AB - The large majority of members of the family Potyviridae are aphid-transmitted. However, 17 viruses whose vectors are unknown have been classified as members of the genus Potyvirus. Loss of aphid transmissibility has been observed in some strains of several potyviruses. There are currently 11 members of the Potyviridae whose vectors are not aphids. These viruses with non-aphid vectors exhibit most of the characteristics of the family. Viruses of the Potyviridae induce cytoplasmic cylindrical inclusions in their hosts whether their vectors are aphids, non-aphids, or are unknown. The virus genome produces the inclusion protein and thus the viruses have related inclusion body gene sequences. Non aphid-transmitted viruses of the Potyviridae also are serologically related to aphid-transmitted potyviruses. PMID- 1450749 TI - Potyviridae: genus Rymovirus. AB - The genus Rymovirus of the family Potyviridae is comprised of seven rod-shaped viruses with the shared characteristic of being transmitted by mites. Aside from this distinguishing feature, rymoviruses are similar to aphid-transmitted potyviruses in that they share a similar particle morphology, some similar antigenic determinants, similar physico-chemical properties, the ability to induce the formation of cytoplasmic cylindrical inclusions, and the ability to infect only graminaceous hosts. In vitro translation studies with wheat streak mosaic virus (WSMV) suggest that this rymovirus uses a potyviral proteolytic processing strategy to express the 3' terminal capsid protein. At the molecular level, limited nucleotide sequence data for WSMV show similarities with aphid transmitted potyviruses in the potyviral capsid protein, large nuclear inclusion and cylindrical inclusion regions. Thus, given the similarities between the rymoviruses and the potyviruses, it is appropriate to include this genus within the family Potyviridae. PMID- 1450750 TI - How important is genome division as a taxonomic criterion in plant virus classification? AB - The number of nucleic acid components that constitute a virus genome has been used as an important discriminatory character in defining groups of plant viruses. However, with some virus groups, in particular potyviruses, recent results of nucleotide sequencing have reinforced previously deduced tentative relationships among viruses with different numbers of genome parts. A convenient solution is to classify these different types into groups or genera within a family (e.g. Potyvirus and Bymovirus in the family Potyviridae). PMID- 1450751 TI - Sequence data as the major criterion for potyvirus classification. AB - Recent knowledge of the structure of the potyvirus particle and its components appears to have resolved what was thought to be an intractable problem of plant virology. This review describes how coat-protein and gene sequence data can be used to provide an hierarchical classification of potyviruses. This classification puts the aphid and non-aphid-transmitted potyviruses into a single family, divides this family into four genera that correspond to the four modes of vector transmission, discriminates distinct potyvirus species from strains, and provides a basis for the formation of subgroups composed of closely related species within a genus. PMID- 1450752 TI - The recombinative nature of potyviruses: implications for setting up true phylogenetic taxonomy. AB - Sequence comparisons reveal that positive-strand RNA viruses not only evolve by divergence from common ancestors but also by interviral recombination. A considerable number of these viruses, exemplified by the family Potyviridae, can in fact, be regarded as successful products of a number of recombination events. It is concluded that the recombinative character of RNA viruses will hamper any attempt to set up a true phylogenetic taxonomy. It is advisable, therefore, to avoid the introduction of any taxon higher-than-family in virus taxonomy. PMID- 1450753 TI - The general properties of potyviruses. AB - The criteria used during the past three decades for including viruses in the potyvirus group are briefly discussed and evaluated. The biological and physico chemical properties of the viruses transmitted by aphids, mites, whiteflies, or the fungus Polymyxa graminis are reviewed, and the taxonomic value of their molecular properties in regrouping the viruses into four groups or genera within the family Potyviridae is discussed. PMID- 1450754 TI - Nomenclature and relationships of some Brazilian leguminous potyviruses related to bean common mosaic and/or passionfruit woodiness viruses. AB - The main Brazilian literature of the last 10 years on potyviruses of leguminous plants related to bean common mosaic virus (BCMV) and/or to passionfruit woodiness virus (PWV) is discussed and summarized. The viruses dealt with are canavalia acronecrosis, mosaico de canavalia, cassia yellow spot, cowpea green vein-banding, cowpea rugose mosaic and cowpea severe mottle. The viruses have similar biological properties, such as a host range restricted mainly to the Leguminosae, aphid transmission, seed transmission in leguminous plants, and various degrees of serological relationships with BCMV and PWV. PMID- 1450755 TI - Potyviruses, chaos or order? AB - At first potyviruses were easily distinguished by biological and serological properties because only a few were known and information on their host ranges was limited. The first evidence of serological cross reaction between two of these viruses was reported in 1951 and was further corroborated for three obviously distinct members of the group in 1960. In 1968 attention was drawn to the fact that some legume and non-legume potyviruses have much wider host ranges than previously known and that within the potyvirus group there is as much biological variation within viruses and overlap between viruses as there is in serology. The concept of continuity within the group was soon supported by others and became known as the "continuum hypothesis." Results with highly sensitive serological methods using polyclonal antisera were conflicting, and nucleic acid hybridization techniques did not unambiguously discriminate between potyviruses. Recent results, obtained with antibodies directed toward epitopes located in the N-termini of the coat proteins of potyviruses, suggest that there are ways to more definitely group strains of one potyvirus and distinguish them from other potyviruses. However, there are exceptions to this rule, as in the case of bean yellow mosaic virus and clover yellow vein virus which are clearly distinct in host range, inclusion bodies, and migration velocity of coat protein, but which still react with antibodies to the N-terminal epitopes of one virus. So the question remains of whether coat-protein properties, especially the serological reactivity of N-termini, which do not alter overall virus integrity when lost, sufficiently represent the genome of a pathogenic virus entity as a single criterion for classification. PMID- 1450756 TI - Ecology and taxonomy of some European potyviruses. PMID- 1450757 TI - Relationships among iris severe mosaic virus (ISMV) isolates. AB - The ISMV isolates studied so far, have been found to be indistinguishable both by serological and hybridization assays. Therefore, the different symptoms induced by these isolates may be based on only minor molecular changes. PMID- 1450758 TI - A comparison of pepper mottle virus with potato virus Y and evidence for their distinction. AB - Pepper mottle virus (PepMOV) was identified as a distinct potyvirus infecting peppers in Arizona and Florida in the 1970's. The distinction of PepMoV from potato virus Y (PVY) has recently been challenged on the basis of sequence comparisons of the coat proteins and of the 3' nontranslated regions of the viral RNAs. We summarize the biological, cytological, serological, and in vitro translational studies which compare the apparent differences, and also similarities, between PepMoV and PVY. We conclude that although PepMoV may be more closely related to PVY than to other known potyvirus, PepMoV should be maintained as a separate virus on the basis of its distinctive characteristics. PMID- 1450759 TI - Is pepper mottle virus a strain of potato virus Y? AB - On the basis of serological properties and host plant reactions pepper mottle virus (PepMoV) has been classified as a potyvirus related to, but distinct from, other pepper-infecting potyviruses, potato virus Y (PVY) and tobacco etch virus (TEV). Recent amino acid and nucleotide sequence data show that PepMoV is more closely related to PVY than previously assumed. PepMoV shows a high degree of homology to various PVY strains in both the coat protein and the 3' non translated sequences, while unrelated potyviruses are generally less homologous in these regions. Detailed coat-protein amino acid sequence and 3' non-translated region (3' NTR) nucleotide sequence comparisons described in this paper confirm the close relationship between PepMoV and PVY and it is concluded that the isolate sequenced indeed represents a strain of PVY. Sequence data for several strains of PVY gave two groups with closer relationships among strains in a group than between groups. PMID- 1450761 TI - A viewpoint on the taxonomy of potyviruses infecting sugarcane, maize, and sorghum. AB - The value of taxonomy lies in its ability to communicate concepts and relationships. Our present concepts of the poaceous potyviruses, based on their biology, serology, and biochemistry, identify four viruses that can be distinguished by each characteristic. Identifying these as four distinct viruses has important implications for disciplines such as epidemiology, plant breeding, and diagnostics. PMID- 1450760 TI - Evidence that pepper mottle virus and potato virus Y are distinct viruses: analyses of the coat protein and 3' untranslated sequence of a California isolate of pepper mottle virus. AB - Pepper mottle virus (PepMoV) is a member of the large and complex genus Potyvirus, and is classically distinguished from other members of the genus by differential host range and cytopathology as well as serology of the coat protein and cytoplasmic inclusion body proteins. Here we report the deduced amino acid sequence of the coat protein of a California potyvirus identified by a variety of classical methods as PepMoV (PepMoV C). Comparison of the 3' untranslated nucleic acid sequence and the deduced coat-protein amino acid sequence of the PepMoV C isolate with those of PVY and other potyviruses indicates that PepMoV C is sufficiently diverged to be considered a distinct virus species. Thus, comparative sequence analyses of the PepMoV C isolate support earlier serological and biological evidence that PepMoV and PVY are distinct viruses. PMID- 1450762 TI - Differentiation of the four viruses of the sugarcane mosaic virus subgroup based on cytopathology. AB - A cytological comparison has been made of representative isolates of johnsongrass mosaic (JGMV), maize dwarf mosaic (MDMV), sorghum mosaic (SrMV) and sugarcane mosaic (SCMV) viruses. These four viruses now encompass the complex of virus strains which were formerly considered as strains of sugarcane mosaic and/or maize dwarf mosaic viruses. The structure of the cytoplasmic cylindrical inclusions induced by these viruses, together with other cytological alterations, allow the four viruses to be distinguished. Pinwheels, scrolls and laminated aggregates were produced only by SCMV whereas JGMV, MDMV, and SrMV produced only pinwheels and scrolls. SrMV produced amorphous cytoplasmic inclusions which are not produced by JGMV and MDMV. The latter two were rather similar in cytological effects except that the SCMV-JG (U.S.A.) isolate of MDMV produced aggregates of needle-like structures in the cytoplasm which were not found with JGMV and the other MDMV isolates. The specific cytological effects induced by these viruses thus corroborate the recent classification of these viruses based mainly on the properties of the coat-protein gene, the 3' noncoding nucleotide sequences, and host reactions. PMID- 1450763 TI - Present status of the sugarcane mosaic subgroup of potyviruses. AB - Until recently, sugarcane mosaic virus (SCMV) was believed to be a single potyvirus consisting of a large number of strains, differing from each other in certain biological and antigenic properties. The use of affinity-purified polyclonal antibodies directed towards the surface-located, virus-specific amino termini of the coat proteins showed that 17 strains from Australia and the United States represented four distinct potyviruses, namely johnsongrass mosaic virus (JGMV), maize dwarf mosaic virus (MDMV), sorghum mosaic virus (SrMV) and SCMV. Comparisons of strains from each of these four viruses on the basis of reactions on differential sorghum and oat cultivars, cell-free translation of RNAs, morphology and serology of cytoplasmic cylindrical inclusions, amino acid sequence and peptide profiling of coat proteins, 3' non-coding nucleotide sequences, and molecular hybridization with probes corresponding to the 3' non coding regions, resulted in exactly the same taxonomic assignments as obtained using amino-terminal serology. These results further confirm that the former sugarcane mosaic virus actually consists of four distinct viruses and show that MDMV, SrMV, and SCMV are more closely related to each other than they are to JGMV. Because these four viruses are closely related but distinct, formation of a sugarcane mosaic subgroup in the genus Potyvirus would be appropriate. PMID- 1450764 TI - Bean yellow mosaic virus subgroup; search for the group specific sequences in the 3' terminal region of the genome. AB - In order to examine relationships among viruses of the bean yellow mosaic subgroup of the Potyvirus genus, several isolates of bean yellow mosaic virus (BYMV) and clover yellow vein virus (C1YVV) were compared by amino acid sequence of the coat protein and nucleotide sequence of the 3' terminal non-coding region. The sequence comparisons showed that BYMV and C1YVV were distinct viruses but had close affinity to each other (85-95% homology among isolates of a virus but 70 77% homology between viruses), justifying establishment of the BYMV subgroup. There was an oligonucleotide consensus sequence present in the 3' terminal non coding region of all potyviruses examined. This consensus sequence divided the potyviruses into three groups whose significance is not clear. PMID- 1450765 TI - A proposal for a bean common mosaic subgroup of potyviruses. AB - In order to elucidate the taxonomic positions of bean common mosaic virus (BCMV) and blackeye cowpea mosaic virus (B1CMV), several strains of these viruses were compared on the basis of host ranges, antigenic properties established with antisera to virions and to N-terminal peptide domains of their coat proteins, and high performance liquid chromatographic peptide profiles. The comparison includes three strains of BCMV, viz. NL1, NL3 and NY15, four strains of B1CMV, viz. Fla, Ind, NR, and W, and the Moroccan isolate (Mor) of cowpea aphid-borne mosaic virus (CABMV), formerly designated as B1CMV-Mor. Based on these parameters, Fla, NR, and W are strains of one virus, whereas NL3, Ind and CABMV-Mor (and possibly NL1 and NY15) are separate viruses. In view of these characteristics which allow similar viruses to be separated, we propose that these viruses be included in a bean common mosaic subgroup of the genus Potyvirus. PMID- 1450766 TI - Serological and biological relationships among viruses in the bean common mosaic virus subgroup. AB - Bean common mosaic virus (BCMV), blackeye cowpea mosaic virus (B1CMV), cowpea aphid-borne mosaic virus (CABMV), azuki bean mosaic virus (AzMV), and peanut stripe virus (PStV) are five species of the genus Potyvirus, family Potyviridae which are seed-transmitted in beans or cowpeas. Eighteen isolates of BCMV, five isolates of B1CMV, four isolates of CABMV, and one isolate each of AzMV, and PStV were compared serologically using a panel of 13 monoclonal antibodies (MAbs) raised against BCMV, B1CMV, CABMV, or PStV in indirect enzyme-linked immunosorbent assay (ELISA). Four MAbs detected all virus isolates; one detected all isolates except those of CABMV. Three MAbs were specific only for serotype A isolates of BCMV. Four MAbs detected all serotype B isolates of BCMV plus all isolates of B1CMV, AzMV, and PStV. None of the antibodies distinguished among these four viruses. However, in biological tests with 11 bean cultivars selected for differentiating BCMV pathotypes, all isolates of B1CMV, AzMV, and PStV could be differentiated from the BCMV serotype B isolates by their reactions on a few bean cultivars in host group I and the cowpea cultivar California Blackeye #5. Potential problems that can arise from the use of nonauthenticated isolates are also discussed. PMID- 1450767 TI - Strains of bean common mosaic virus consist of at least two distinct potyviruses. AB - Bean common mosaic virus (BCMV) consists of a large number of pathotypes and strains which have largely been identified by their characteristic interactions with a selected number of differential bean cultivars. The relationships among these strains and other potyviruses that infect legumes are complex, with indications that BCMV, blackeye cowpea mosaic virus (BlCMV) and azuki bean mosaic virus (AzMV) may be strains of the one virus. Using high performance liquid chromatographic peptide profiles of coat-protein digests, the NL3 and NY15 strains of BCMV were compared with each other, with the Type and W strains of BlCMV and with the mild mottle strain of peanut stripe virus (PStV). The results suggest that BCMV-NL3 and BCMV-NY15 are distinct potyviruses, not strains of the one virus, and that BCMV-NY15 is a strain of the same potyvirus that includes BlCMV, PStV, AzMV and three potyvirus isolates (74, PM, PN) from soybeans. PMID- 1450768 TI - A summary of potyvirus taxonomy and definitions. AB - The current taxonomic status of the family Potyviridae is presented with suggestions for resolving some taxonomic problems. Terms such as strain, pathotype, serotype, variant, mutant, and isolate are discussed in relation to the family. PMID- 1450769 TI - What is a virus? AB - The earlier reluctance of some plant virologists to use the term "virus species" has been overcome and the species has now been accepted as the basic unit in virus classification. A virus species is a polythetic class of viruses that constitutes a replicating lineage and occupies a particular ecological niche. Because of the polythetic nature of virus species, there is no single property, such as a particular level of genome homology, that could be used as the sole criterion for delineating individual virus species. PMID- 1450770 TI - Serology of potyviruses: current problems and some solutions. AB - The serological relationships among members of the family Potyviridae are extremely complex and inconsistent. Variable cross-reactivity of polyclonal antisera, unexpected paired relationships between distinct viruses, and lack of cross-reactions between some strains are the major problems associated with the serology of potyviruses. Recent biochemical and immunochemical investigations of coat proteins have established the molecular basis for potyvirus serology and provided explanations for most of the problems with serology of potyviruses. Information from these studies has also formed the basis for the development of several novel approaches to the accurate detection and identification of potyviruses. However, even these novel approaches are not without drawbacks and some of them cannot be applied easily in plant virus laboratories, since they require prior sequence information and facilities for peptide synthesis. These findings suggest that serology is an imperfect criterion for the identification and classification of potyviruses. PMID- 1450771 TI - Polyclonal reference antisera may be useful for the differentiation of potyvirus species. AB - Attention is directed to the usefulness of polyclonal antisera for the identification of potyviruses on the species level. A scheme for the preparation of such antisera is given. PMID- 1450772 TI - Proteolytic cleavage of the N-terminal region of potyvirus coat protein and its relation to host recovery and vector transmission. AB - The proteolytic cleavage of potyvirus coat N-terminal region is discussed with relation to host recovery and aphid transmission. The relationship of this coat protein region and the HC, may affect the host range and should be considered in this virus group classification. PMID- 1450773 TI - Some unusual serological reactions among potyviruses. AB - The determination of relationships among and the identification of potyviruses with polyclonal antibodies does not always lead to a proper conclusion. The potyvirus specific monoclonal PTY 1 does not detect all potyviruses tested. PMID- 1450774 TI - Serological relationships involving potyviral nonstructural proteins. AB - This report represents a compilation of many of the publications on antigenic properties of potyviral-specified nonstructural proteins. Polyclonal antisera have been prepared for use in characterization of six nonstructural proteins. These include antisera to the cylindrical inclusion proteins of at least 28 potyviruses, to small nuclear inclusion protein (protease) of four potyviruses, to large nuclear inclusion protein (putative replicase) of three viruses, helper component-protease or amorphous inclusion protein of at least four viruses, to the P1 protein (located at the N-terminus of the polyprotein) of one virus, and to the P3 protein (located between helper component protease and cylindrical inclusion protein) of one virus. Monoclonal antibodies also have been prepared to several of these nonstructural proteins. The evidence thus far indicates that cylindrical inclusions of different potyviruses have both conserved and unique epitopes. Nuclear inclusion proteins and amorphous inclusion proteins also may have conserved and unique epitopes. Antigenic relationships of potyviral nonstructural proteins have potential for the identification and classification of potyviruses. PMID- 1450775 TI - The question of nursing scholarship. PMID- 1450776 TI - Emerging role for nurses in health communication. PMID- 1450778 TI - The real experts. PMID- 1450777 TI - Nursing education and professional autonomy. PMID- 1450779 TI - Legal implications of the Patient Self-Determination Act. AB - Passage of the Patient Self-Determination Act provides professional nurses with the opportunity to expand their existing roles of educator and advocate. Institutional policies and procedures implementing the Act should be flexible enough to permit registered nurses to answer questions about the right to refuse medical treatment and how to implement that right. Patients and their families have been asking nurses these questions since before the Quinlan case was decided in 1976. PMID- 1450780 TI - The Patient Self-Determination Act: the ethical dimensions. AB - Advanced, sophisticated technology, rising health care costs, and consumerism all combined to drive the development of the Patient Self-Determination Act. Ethical implications include, but are not limited, to the principles of autonomy and beneficence. Paternalism is also discussed as a compromise to autonomy. Caring is used to focus on the contextual perspective of both patients and nurses for ethical decision making. Implications for future ethical practice conclude the discussion. PMID- 1450781 TI - Carolyn Coolidge: caring for the Chinese elderly at On Lok. PMID- 1450782 TI - Family perspective on the necessity for advance medical directives. AB - Although our parents made no written advance medical directives before becoming terminally ill, with the support of the nursing staff we were able to assist them in their quest for a natural death with dignity. This article presents some of the dilemas faced by families in making end-of-life decisions. The author acknowledges the importance of permission for and support of the decision making by other health care providers, and reflects that advance directives would have facilitated the process. PMID- 1450783 TI - Advance care directives: counseling the patient and family in the primary care setting. AB - NPs are in an excellent position to provide primary care patients with the appropriate counseling for the development of required advanced care directives before the onset of serious illness and hospitalization. Discussion of how and whom to counsel assists the NP in undertaking this important responsibility encountered by primary care providers. PMID- 1450784 TI - Organ donation authorization: an advance medical directive. AB - Primary health care providers may increase the number of organ donations by providing an opportunity for authorization during a health care visit. Lack of authorization prevents many recipients from the benefits of life saving transplants. PMID- 1450785 TI - Health decisions: maintaining control of health care choices. AB - Advanced technology sometimes prolongs life without improving the quality of life. California's Durable Power of Attorney for Health Care (DPAHC) provides individuals with a tool to maintain control over their future health care should they become unable to make health care decisions. California Health Decisions (CHD) developed a comprehensive workshop designed to inform people about the DPAHC and its options and has played a leadership role in educating health care professionals, the general public, seniors, and employee groups. CHD has set a goal of helping 1 million Californians complete a DPAHC by 1995. This article describes the issues involved in implementing the educational goals to achieve this objective. PMID- 1450786 TI - Who speaks for the children: consent for treatment of minors. PMID- 1450787 TI - Understanding current federal reimbursement: what's next? PMID- 1450788 TI - Nonsteroidal anti-inflammatory drugs: a review for the 1990s. PMID- 1450789 TI - Standard algorithm for oscillometric blood pressure measurement. PMID- 1450790 TI - Effective technology management in a cost-conscious environment. PMID- 1450791 TI - Utilizing a systems approach to categorize device-related failures and define user and operator errors. PMID- 1450792 TI - Microcontroller-based real-time QRS detection. AB - The authors describe the design of a system for real-time detection of QRS complexes in the electrocardiogram based on a single-chip microcontroller (Motorola 68HC811). A systematic analysis of the instrumentation requirements for QRS detection and of the various design techniques is also given. Detection algorithms using different nonlinear transforms for the enhancement of QRS complexes are evaluated by using the ECG database of the American Heart Association. The results show that the nonlinear transform involving multiplication of three adjacent, sign-consistent differences in the time domain gives a good performance and a quick response. When implemented with an appropriate sampling rate, this algorithm is also capable of rejecting pacemaker spikes. The eight-bit single-chip microcontroller provides sufficient throughput and shows a satisfactory performance. Implementation of multiple detection algorithms in the same system improves flexibility and reliability. The low chip count in the design also favors maintainability and cost-effectiveness. PMID- 1450793 TI - A computerized system to evaluate volumetric infusion pumps. AB - A computerized system was developed to examine the performance characteristics of infusion pumps. This system collects solution delivered by an infusion pump through an intravenous needle into a collection vessel. Using an inductor-type weight sensor and a semiconductor type of strain-gauge pressure sensor, the weight of the collection vessel and the pressure at the needle were monitored over a specific period (the sampling time), and changes in pressure, flow rate, and volume of fluid were calculated. This system was applied to five volumetric infusion pumps with different pumping mechanisms. Test conditions involved two different solutions, two sizes of needle gauge, and seven flow rates, for a total of 28 measurements per pump. Results showed considerable variation in the infusion pumps' performances based on differences in these indices. Use of an inductance weight sensor as a means to evaluate gravimetric performance appears to be an improvement over conventional methods, which use analytical balances for data generation. The results indicate that this system will be useful in evaluating the performances of commercially available infusion pumps as well as those in development. PMID- 1450794 TI - Quantitative measurement of ventilation at the mouth and nose with heat sensors. AB - Airflow at the nose and mouth is routinely measured during polysomnography for the evaluation of respiratory disturbances during sleep. The usual monitoring device is a small thermocouple placed in front of the nose and mouth that qualitatively detects airflows in or out. A more accurate pneumotachometer on a tight-fitting mask is less frequently used because of the discomfort that is introduced and its potential interference with sleep. The authors tested ten heat sensing devices modified to increase accuracy without increasing discomfort. The designs of these ventilation monitors differed in choices of specific heat detector, techniques of mounting on the face, and types of heat-trapping covers employed. The goal was to find a comfortable oronasal monitor and to define a procedure that could identify those units that generate signals approaching quantitative ventilatory flow. The signal from each device was compared with a "standard" signal derived from respiratory belts during contrived respiratory maneuvers that assessed specific potential sensing problems. The devices behaved differently, and design perturbations could be controlled to construct flow detectors to closely match actual flow. The more accurate devices could be as comfortable as commonly used monitors that do not have the enhanced accuracy. The principles and techniques described for improving the measurement of oronasal ventilation by heat sensor can be invoked to develop monitors that can closely measure actual quantitative ventilatory flow. PMID- 1450795 TI - The clinical terms project. PMID- 1450796 TI - Upper gastrointestinal complaints and complications in chronic rheumatic patients in comparison with other chronic diseases. AB - The aim of this study was to compare the frequency of upper gastrointestinal (GI) complaints and complications between chronic rheumatic patients who are most often non-steroidal anti-inflammatory drugs (NSAIDs) users and patients with other chronic conditions. In this comparison we took into account known risk factors for upper GI disease. To achieve the study aims we performed a combined cross-sectional and retrospective study. We therefore interviewed by means of a standard questionnaire, an index and a reference group, about current upper GI complaints and previous complications. The former group comprises 578 outpatients of the Department of Rheumatology, the latter of 531 outpatients of the Departments of Internal Medicine, Pulmonology, and Cardiology. Although the number of patients in the index group being chronically treated with NSAIDs was very high (62% versus 9% in the reference group: P < 0.00001), no between-group differences were found for the frequency of several current upper gastrointestinal complaints or for the number of upper gastrointestinal investigations ever performed (35% and 37%: NS) or for the use of gastric drugs (14% and 10%: NS). Risk factors for upper GI complaints were not related to NSAID use but with the use of prednisolone, history of duodenal ulcer disease, family history of peptic ulcer disease and female sex. For peptic ulcer disease, bleeding, and gastric surgery, the only difference between the index and reference groups concerned the frequency of gastric ulcers (6.7% and 2.8%: P < 0.005), which was highest in patients with rheumatoid arthritis. Upper GI bleeding had more often been present in male seropositive rheumatoid arthritis patients (13.2% [corrected] and 4.5%: P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450797 TI - The gastroduodenal safety and efficacy of the fixed combination of diclofenac and misoprostol in the treatment of osteoarthritis. AB - A double-blind, randomized, parallel group study was conducted to compare the gastroduodenal safety and antiarthritic efficacy of a fixed combination of diclofenac 50 mg and misoprostol 200 micrograms with that of a combination of diclofenac 50 mg and placebo in patients with osteoarthritis. Three hundred and sixty-one patients with no significant gastroduodenal lesions were enrolled and received study medication two or three times daily for 4 weeks. Post-treatment endoscopic examination of the gastroduodenal mucosa revealed ulcers in 4% of patients in the diclofenac/placebo group compared with none in the diclofenac/misoprostol group (P = 0.015). There were no clinically or statistically significant differences between the two treatment groups in formal assessments of osteoarthritis after either 2 or 4 weeks. It was concluded that diclofenac/misoprostol was associated with significantly less gastroduodenal damage than diclofenac, whilst being as effective as diclofenac alone in the treatment of osteoarthritis. PMID- 1450798 TI - Urinary collagen crosslinks reflect the radiographic severity of knee osteoarthritis. AB - The collagen crosslinks deoxypyridinoline and pyridinoline are indices of mature collagen breakdown and reflect increased bone turnover. Urinary levels were found to be significantly raised in a group of 59 women with knee OA compared to 110 female controls from the general population. Levels of the crosslinks correlated significantly with X-ray grade of all subjects including women from the general population with mild, often asymptomatic, disease. These correlations were not diminished after adjustment for age and weight. PMID- 1450799 TI - Sibship size does not increase the risk of developing rheumatoid arthritis. AB - Although the cause of rheumatoid arthritis (RA) is unknown, one hypothesis is that an infectious episode may trigger the disease and this may occur in childhood. Observational studies performed at least 25 years ago have suggested that the incidence of RA is increased in individuals from large families. We therefore tested this hypothesis using data from a case-control study of 218 females with RA aged 35-70 (mean 58.9 years) and 210 similar aged osteoarthritis (OA) females. Information was obtained by postal questionnaire on sibship size, position in family and sex ratio of siblings. No significant differences were found between the cases and controls for any of these variables. This study did not support the hypothesis that early childhood infection as a consequence of overcrowding is an important factor in the development of RA. PMID- 1450800 TI - Clinical differentiation of oral ulceration in Behcet's disease. AB - Behcet oral ulceration (BOU) is described as being indistinguishable from conventional recurrent oral ulceration (ROU). A clinical comparison between 38 Behcet patients and 38 control ROU cases was effected by completion of a standard questionnaire. Behcet patients reported an increased number of concurrent ulcers and involvement of the soft palate and oropharynx. No differences were detected with respect to duration, frequency, age of onset or family history. In addition, photographs of BOU in 15 patients revealed the concurrence of atypical aphthous and herpetiform varieties. Number, site and appearance of oral ulceration may therefore provide diagnostic features for the development of Behcet's disease. PMID- 1450801 TI - Seronegative arthritis. PMID- 1450802 TI - Lupus comes of age. PMID- 1450803 TI - Injection therapy of superficial rheumatoid nodules. AB - Although intralesional corticosteroid injection of subcutaneous rheumatoid nodules was mentioned in 1968, this simple procedure is not commonly practised. A placebo-controlled, double-blind trial of intralesional corticosteroid injection using 24 rheumatoid nodules from 11 patients was carried out to determine the efficacy and safety of the procedure. Nodules injected with methylprednisolone and lignocaine regressed significantly more than nodules injected with placebo (lignocaine alone). This was consistently shown in all modalities of assessments which included patients' assessments (P < 0.001) and investigator's assessments (P < 0.001) of the percentage change in nodule size, and gross measurements of nodule volumes using a pincer (P < 0.001). Nine of 12 active injections produced > or = 50% loss in nodular volume with complete disappearance of two nodules. This compares with only one out of 12 placebo injections which resulted in > or = 50% loss in nodular volume. The patients found all 12 active injections to be worthwhile compared to only two of 12 placebo injections being worthwhile. The only complication of injection therapy observed was that of pain during the procedure. PMID- 1450804 TI - Papular mucinosis (scleromyxoedema) complicating diffuse systemic sclerosis: clinical features and electron microscope observations. AB - Papular mucinosis (scleromyxoedema) is an uncommon disorder characterized by generalized papular eruption and cutaneous induration, which may be associated with a variety of extracutaneous manifestations. Although scleroderma and papular mucinosis share many features, they are clinically and histologically distinct entities. We report here a patient with diffuse scleroderma who developed superimposed papular mucinosis. Degranulating mast cells were a prominent ultrastructural finding in the involved skin. The occurrence of scleroderma and papular mucinosis, two uncommon cutaneous indurative diseases, in the same patient has not been described previously. PMID- 1450805 TI - The evolution of a case of overlap syndrome with systemic sclerosis, rheumatoid arthritis and systemic lupus erythematosus. AB - An unusual case of overlap syndrome which evolved over a 12-year period is described. The patient initially presented with limited cutaneous systemic sclerosis. She then developed seropositive erosive rheumatoid arthritis and subsequently vasculitis with positive lupus serology. There was no evidence that she had mixed or undifferentiated connective tissue disease, and antibody to ribonuclearprotein was negative. This unusual combination of connective tissue disorders in one patient is reported and the literature is reviewed. PMID- 1450806 TI - Central neurological manifestations of primary Sjogren's syndrome. PMID- 1450807 TI - Renal vein thrombosis in Chinese systemic lupus erythematosus with high titre anticardiolipin antibody. PMID- 1450808 TI - 'Snake oil'. PMID- 1450809 TI - Extracorporeal photochemotherapy. PMID- 1450810 TI - Chloroquine-induced vitiligo in a patient with juvenile onset rheumatoid arthritis. PMID- 1450811 TI - Juvenile arthritis and coeliac disease. PMID- 1450812 TI - Gouty arthropathy and synovial uric acid. PMID- 1450813 TI - Efficiency of a lead-containing tie for radiation protection of the thyroid gland. AB - During fluoroscopy the examiner is usually protected by a radiation-reducing body shield, leaving the thyroid unprotected. The fact that the thyroid is located in a region of the neck usually covered by the shirt collar led to the idea of designing a tie with lead core, providing easy and "decorative" reduction of the radiation dose. Sonographic examinations were carried out in 20 volunteers (10 men, 10 women) to determine the size of the gland and its coverage by such a tie. The reduction of the surface and organ dose was assessed using film dosimetry with scattered radiation, the body of the examiner being simulated by an Alderson phantom. On average 88% of the thyroid gland surface area was covered. Surface dose was reduced to 1%, and organ dose to 10% of the value without the protection tie. PMID- 1450814 TI - Measuring radiation exposure during percutaneous drainages: can shoulder dosemeters be used to estimate finger doses? AB - Some previous studies have shown remarkably high finger doses to radiologists performing percutaneous drainage under fluoroscopy. To assess the possible need for extra finger dosemeters in addition to the general dosemeter, radiologists' and assistants' radiation exposure at both shoulders and at the third fingers of both hands were recorded using thermoluminescent dosemeters during 27 interventional drainage procedures. Under couch screening was used. Mean dose rates were calculated by dividing the doses by the screening time. The dose rates for the sites measured were correlated with each other. The radiologists' bilateral finger dose rates did not correlate with each other; nor did dose rates between the left shoulder and the right hand. The radiologists' dose rates at both shoulders, however, correlated with each other, as did the shoulder dose rates with the dose rates at the ispilateral hand. The right shoulder dose rates correlated with the left hand dose rates. The assistants' dose rates at the places of measurement all showed significant correlations with each other. It is therefore concluded that radiologists involved in percutaneous drainages should use finger dosemeters on both hands; for assistants this may not be necessary. PMID- 1450815 TI - Effect of diatrizoate on the function of the isolated perfused rat kidney. AB - The mechanism of the nephrotoxicity of water-soluble contrast media (WSCM) remains ill defined. We have studied the effect of diatrizoate on the isolated perfused rat kidney (IPRK). Emphasis was on the effect of low- and high-dose diatrizoate on glomerular filtration rate (GFR), renal perfusate flow (RPF), fractional excretion of albumin (FE Alb) and fractional reabsorption of sodium (FR Na). The addition of diatrizoate to the IPRK led to a dose-dependent biphasic change in RPF and GFR characterized by an initial transient increase followed by a marked and sustained decrease. Diatrizoate induced a diuresis and a parallel increase in urinary sodium excretion (fall of FR Na). Fe Alb was also increased in kidneys exposed to diatrizoate. Electron microscopy of a control kidney showed preservation of cellular architecture, which contrasted with the observed cytoplasmic vacuolation of proximal tubular cells after perfusion with diatrizoate. This study confirms a direct effect of WSCM on the function of the IPRK. In this experimental model, diatrizoate reproduces the effects observed in vivo on GFR and renal perfusion. PMID- 1450816 TI - Stage IB cervical carcinoma: a clinical audit. AB - All patients with FIGO Stage IB cervical cancer registered with the Department of Clinical Oncology at the Western General Hospital, Edinburgh, during the 6 years from 1979 to 1984 have been reviewed, as part of a continuing programme of clinical audit. Of the 140 patients with Stage IB disease, 68 (49%) were treated by primary surgery of whom 44 (31%) also received adjuvant radiotherapy. Radical radiotherapy was the definitive treatment for 69 patients (49%). Three patients (2%) were not treated with curative intent. The crude 5-year survival rate for all cases was 72% and the cause-specific 5-year survival rate was 78%. Local tumour control at 5 years was 72%. There was no significant difference in outcome between the surgically treated and irradiated groups of patients. Age, histology and nodal status did not influence outcome. Irradiated patients with bulky tumours fared significantly worse than the other patients who received radical radiotherapy. Multivariate analysis of all patients revealed no significant independent prognostic variables. Primary surgery appears to confer no benefit over radical radiotherapy in terms of either survival or local control. Treatment related late bladder and bowel morbidity was, however, significantly worse in irradiated patients. PMID- 1450817 TI - Calcium antagonists protect mice against lethal doses of ionizing radiation. AB - Currently available radioprotectors are poorly tolerated in man and the general use of aminothiol radioprotectors is compromised by their side-effects. In a search for less toxic radioprotective agents, diltiazem, a calcium antagonist with a benzothiazepine structure, was found to protect mice against a lethal (LD100) gamma radiation dose allowing survival of up to 93%. Dihydropyridine calcium antagonists such as nifedipine, nimodipine, isradipine and nitrendipine also provided radioprotection. Calcium antagonists might attenuate radiation induced injury by inhibiting cellular calcium overload, subsequent to cell membrane damage caused by radiation-generated free radicals. In view of their good tolerance, calcium antagonists may be applied safely in situations of radiation exposure, including radiotherapy and internal radionuclide contamination. These calcium antagonists may also be viewed in other contexts where free radicals are implicated in pathological processes. PMID- 1450818 TI - Phantoms for evaluating the performance characteristics of bone densitometers. PMID- 1450819 TI - Segmental reversal of intrahepatic portal flow due to a liver metastasis. PMID- 1450820 TI - Intrarenal varices mimicking hydronephrosis. PMID- 1450821 TI - Transitional cell carcinoma of the bladder associated with Crohn's disease: case report and review of the literature. PMID- 1450822 TI - The swiss cheese brain. PMID- 1450823 TI - Demonstration by computed tomography of a case of internal small bowel herniation. PMID- 1450824 TI - Caecal herniation through the foramen of Winslow: diagnosis by computed tomography. PMID- 1450825 TI - Dense bones. PMID- 1450826 TI - Correlations between alpha/beta and T1/2: implications for clinical biological modelling. PMID- 1450827 TI - The role of 99Tcm-HMPAO white cell imaging in suspected orthopaedic infection. PMID- 1450828 TI - Coil embolization using a saline flush technique. PMID- 1450829 TI - Fluid levels in a spinal aneurysmal bone cyst following biopsy. PMID- 1450830 TI - Direct coronal computed tomography of the temporomandibular joint in patients with rheumatoid arthritis. AB - Direct coronal computed tomography (CT) of the temporomandibular joint (TMJ) was performed in 26 patients with rheumatoid arthritis (RA) and 26 control subjects. Erosions and cysts of the mandibular condyle had a significantly higher frequency in the RA group than in the control group (p < 0.05) but there was no significant difference in the incidence of other abnormalities. Bone changes were bilateral in RA. A wide range of CT abnormalities was present in patients with RA and in the control group. There are no CT abnormalities specific for RA, but the incidence of erosions and cysts of the mandibular condyle was significantly higher in the RA group and should suggest the diagnosis. PMID- 1450831 TI - Vasoconstriction by angiographic contrast media in isolated canine arteries. AB - To study the mechanism of the pain produced by contrast media (CM) in peripheral arteriography, we examined the direct effects of low concentrations (1.85-100 mg I/ml) of CM (diatrizoate, iopamidol, ioxaglate, and iotrolan) on helically cut strips of canine blood vessels taken from six different regions. We found that: (a) low concentrations of CM induced vasoconstriction. (b) This occurred immediately after the application of CM and produced sustained constriction. (c) The constriction produced in arteries was dose-dependent. (d) The production and intensity of constriction in the arterial strips differed as follows: cranial mesenteric artery > renal artery > femoral artery > common carotid artery > thoracic aorta > coronary artery. The effects of the CM were, in order of magnitude: diatrizoate > iopamidol > ioxaglate > iotrolan. Differences between CM corresponded with the differences in osmolality of the CM solutions. (e) Low concentrations of meglumine and mannitol also produced vasoconstriction. (f) Constriction caused by all drug samples used was reversible, but the process of relaxation to the original tension was much slower in CM-treated arterial strips than in the other strips. From these results, we confirmed that the incidence and degree of vasoconstriction produced by all drug samples used in this experiment depended on solution osmolality, rather than on chemotoxicity or ionicity. We discuss the physiological mechanism of these results and stress the importance of CM hyperosmolality in vasoconstriction and vascular pain production. PMID- 1450832 TI - Percutaneous drainage of splenic abscesses: an effective and safe procedure. AB - Percutaneous drainage of splenic abscesses has not yet become a common procedure due to the potential risk of bleeding and the danger of damage to neighbouring organs. We present our experience of percutaneous drainage in eight patients with splenic abscesses. Four patients were treated by therapeutic percutaneous needle aspiration of the fluid collection, and four by percutaneous trocar catheter insertion. All procedures were guided by ultrasound or computed tomography. The procedure was successful in all eight patients with no complications. PMID- 1450833 TI - One-view versus two-view mammography in baseline screening for breast cancer: a review. AB - Two-view mammography is generally preferred as an initial screening examination because the number of missed carcinomas and false positive results in one-view mammography is considered too large. The present review was performed to assess the difference in screening quality between one- and two-view mammography. Nineteen previous studies were reviewed and differences in sensitivity as well as specificity between two-view and one-view mammography were calculated. The results ranged from -5.7% to 19.4% (median 3.9%), and 2.7% to 36.1% (median 14.8%), respectively, and indicate a higher screening quality of two-view mammography. However, in the studies considered there is a large variation in study population, screening tests used and assessment of disease outcome, which makes the numerical results less conclusive. None of the studies provided adequate information for deciding whether two-view mammography in baseline screening for breast cancer is preferable to one-view mammography. If a screening programme using one-view mammography has already achieved high sensitivity and specificity, the value of an additional craniocaudal view is only marginal. PMID- 1450834 TI - Sonography in thyroid carcinoma in children. AB - This paper reviews the clinical, sonographic and pathological findings of 20 children with thyroid carcinoma in an attempt to determine the value and limitations of sonography in thyroid neoplasms in this age group. Although sonography is an excellent technique for the evaluation of thyroid disorders and masses, certain limitations must be kept in mind. Microscopic foci of tumour might be missed and sonography cannot predictably differentiate benign from malignant disease. Previous radiation exposure should increase the level of suspicion for malignancy. PMID- 1450835 TI - Enlarged mediastinal lymph nodes in the fibrosing alveolitis of systemic sclerosis. AB - The aim of this study was to determine the prevalence of enlarged mediastinal lymph nodes in systemic sclerosis (SSc) and relate this to the extent of pulmonary disease and disease activity as judged by high resolution computed tomography (HRCT). The HRCT scans of 78 patients with SSc were reviewed. The extent of lung disease and HRCT pattern were analysed and CT scans examined on soft tissue window settings for evidence of mediastinal lymph node enlargement. Sixty six (85%) patients had evidence of lung involvement on CT. Enlarged mediastinal lymph nodes were present in 21 (32%) patients with lung involvement but in only 1 (8%) patient without. The prevalence of enlarged mediastinal nodes increased with more extensive lung involvement on CT (p < 0.025), but correlated poorly with the type of CT appearance and concurrent erythrocyte sedimentation rate. Mediastinal lymph node enlargement occurs frequently in patients with SSc, particularly if lung involvement is extensive. PMID- 1450836 TI - Prediction of birthweight by fetal ultrasound biometry. AB - A total of 104 women with singleton pregnancies who were delivered between 37 and 42 weeks gestation had ultrasound scans during the fortnight before delivery. The biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) were measured in all cases. Estimation of fetal weight (EFW) was done by four different methods: using AC alone, AC/BPD, AC/FL and AC/BPD/FL. Results were compared with values of actual birthweights at delivery. There was no significant difference between the mean birthweights of the 47 boy and 57 girl fetuses studied. The EFW(Shepard) method showed the least bias overall: mean percentage error 1.7%, standard deviation (SD) 10.6%. The other three methods significantly underestimated birthweights on average: EFW(Deter), mean error 2.2%, SD 9.3%, p < 0.02; EFW(Campbell), mean error 5.4%, SD 9.5%, p < 0.001; EFW(Hadlock), mean error 5.6%, SD 9.3%, p < 0.001. The percentage error in each group was significantly negatively correlated (p < 0.001) with the scan-delivery interval. Two new equations were generated which gave more accurate predictions for the cases under study using AC, BPD and FL as a combination and also in addition to scan-delivery interval (SDI) in days. PMID- 1450837 TI - The effect of thin K-edge filters on radiation dose in dental radiography. AB - The use of thin K-edge filters has been found to reduce considerably the radiation dose in intra-oral radiography. The aim of this study was to investigate the effect of filtration on the skin entrance dose and several sites (representing organs or areas of interest within the head) along the central beam axis, at other points within the primary beam and at two points just outside the primary beam. The subject was a sliced head phantom (a human skull embedded in tissue-equivalent material) which was exposed to X rays from a conventional dental X-ray unit in the range of tube voltage 55-85 kVp for each of four filter systems. These were 2.7 mm of aluminium alone (the existing total filtration) or with an added 0.1 mm erbium, 0.1 mm yttrium or 0.05 mm niobium metal foils. Measurements of radiation dose were made using thermoluminescent dosemeters (TLD rods) and were adjusted to simulate the exposure resulting from a typical dental radiograph of a maxillary molar. The results suggest that the use of thin K-edge filters significantly reduces the entrance skin dose and to a certain extent reduces the total dose imparted to the head. However, the dose to the ipsilateral orbit at higher tube voltages may be increased. PMID- 1450838 TI - The distribution of medical X-ray doses amongst individuals in the British population. AB - This study has estimated the distribution of diagnostic X-ray doses amongst individuals in the British population by sampling the records kept by general practitioners (GPs) on their patients and the records held by the radiology department of a district general hospital. Deceased patients were chosen in the former case in order to evaluate the dose acquired over a complete lifetime. In each case, several hundred records were sampled. The GP data obtained have enabled an estimate to be made of the likelihood of reaching various dose levels in a lifetime. It is estimated that about 1% of the population has received a lifetime effective dose-equivalent of more than 100 mSv. The largest cumulative dose revealed by the samples of GP and radiology department records was about 200 mSv. The GP data have also shown that the last year of life sees a four-fold increase in the number of X-ray examinations experienced compared with the previous 9 years. The hospital data have allowed an estimate to be made of current rates of dose acquisition amongst the population of a District Health Authority. PMID- 1450839 TI - The use of extracorporeal shock wave lithotripsy for medullary sponge kidneys. AB - A number of patients with medullary sponge kidney recurrently form and pass stones with the risk of developing an obstructive nephropathy. These patients may benefit from extracorporeal shock wave lithotripsy to the medullary collections, as this appears to reduce the frequency of symptomatic stone passage. PMID- 1450840 TI - In vitro inhibition of struvite crystal growth by acetohydroxamic acid. AB - Struvite (MgNH4PO46H2O) crystals were produced by Proteus mirabilis growth in artificial urine, in the presence and absence of the urease inhibitor, acetohydroxamic acid (AHA). In the absence of AHA, struvite crystals assumed an "X-shaped" or dendritic crystal habit due to rapid growth along their 100 axis. When AHA was present, crystal growth, as monitored by phase contrast light microscopy, was greatly slowed, and the crystals assumed an octahedral crystal habit. Scanning electron microscopy revealed that crystals grown in the presence of AHA were pitted on their surface. This pitting was absent in control samples. While most of this inhibition by AHA was due to lowered urease activity, some crystal growth inhibition occurred in struvite produced in the absence of urease activity through NH4OH titration of artificial urine. We conclude that while AHA is primarily a urease inhibitor, it may also disrupt struvite growth and formation directly through interference with the molecular growth processes on crystal surfaces. PMID- 1450841 TI - Pyonephrosis: diagnosis and treatment. AB - A series of 23 confirmed cases of pyonephrosis initially treated by percutaneous nephrostomy drainage were reviewed. Presentation was extremely variable, ranging from sepsis to asymptomatic bacteriuria. Fever, flank pain and leukocytosis were often absent. Ultrasonography was diagnostic in only 3 of 12 patients. In all, 17 patients had associated nephrolithiasis, and 5 patients ultimately required nephrectomy. Renal urine cultures were positive in 16 of 21 instances, with multiple organisms found in 8 of 21, and added bacteriological data not provided by bladder urine cultures in 11 cases. A pre-existing history of urinary tract infection, hypertension and malignancy was common. Percutaneous drainage was a safe, quick and effective diagnostic and therapeutic method. PMID- 1450842 TI - Does DNA flow cytometry give useful prognostic information in renal parenchymal adenocarcinoma? AB - DNA ploidy and S-phase fraction (SPF) were measured by flow cytometry on 381 paraffin blocks from 93 unselected primary renal parenchymal adenocarcinomas (RPA). The results were compared with tumour grade and T category and patient survival, with a mean follow-up of 87 months. Only 21% of the tumours were uniformly diploid and ploidy was heterogeneous in 49% of cases. DNA ploidy and SPF were significantly associated with grade, but not T category of disease. Both flow cytometric parameters were significantly related to survival in a univariate analysis. However, when tumour grade was taken into account, both DNA ploidy and SPF lost their prognostic significance. Thus, neither of these parameters gave prognostic information additional to that provided by tumour grade in unselected cases of primary RPA. PMID- 1450843 TI - Increase in presumptive sensory nerves of the urinary bladder in idiopathic detrusor instability. AB - The density of subepithelial, presumptive sensory nerves in the bladder wall was assessed in 21 women with idiopathic detrusor instability and compared with the density of these nerves in 21 asymptomatic women, using a point-counting technique on sections of bladder biopsies stained for acetylcholinesterase activity. The mean value (+/- S.E.) for the amount of such nerves in patients with detrusor instability (91 +/- 13/mm2) was significantly greater than that from the control group (61 +/- 7/mm2). This suggests that a relative abundance of subepithelial sensory nerves may serve to increase the appreciation of bladder filling, giving rise to the frequency and urgency of micturition which are characteristic of patients with detrusor instability. PMID- 1450844 TI - Loss of sensory neuropeptides in the obstructed human bladder. AB - This is the first investigation of alterations in the innervation of the obstructed human bladder by nerves containing neuropeptides. The patient groups studied were those with stable detrusor function, those with unstable detrusor function, and those presenting with acute retention of urine. Specimens of bladder tissue were taken from the lateral wall of the bladder below the peritoneal reflection. A total of 23 patients was studied (control, n = 4; acute retention, n = 5; stable obstruction, n = 5; unstable obstruction, n = 9). Substance P, calcitonin gene-related peptide and vasoactive intestinal polypeptide levels in the bladder were quantified by immunoassay. The density of innervation of the bladder detrusor by nerves containing these neurotransmitters and by those containing neuropeptide Y and somatostatin was assessed using both semiquantitative and quantitative immunohistochemical techniques. A reduction in the density of innervation by vasoactive intestinal polypeptide, calcitonin gene related peptide, substance P and somatostatin-immunoreactive but not neuropeptide Y-immunoreactive nerve fibres was shown in the obstructed bladder. These findings, combined with the significant reduction in substance P content of the obstructed bladder and in particular of the acute retention bladder, indicate that there may be an afferent nerve dysfunction resulting from prostatic bladder outflow obstruction. PMID- 1450845 TI - Is there still a place for prolonged bladder distension? AB - Over a 2-year period, 31 patients underwent prolonged hydrostatic bladder distension for benign and malignant bladder disease in this unit. Of these, 29 patients had benign functional disorders or bladder contracture, and in 2 patients hydrodistension was performed for complications of treatment for bladder neoplasia. Of the 29 patients with benign disease, 6 observed marked improvement and 8 some improvement in their symptoms, and 12 received no benefit. Patients with detrusor hypersensitivity fared better than those with detrusor instability or interstitial cystitis. A patient with malignant bladder disease died soon after the procedure as a result of a myocardial infarction. Problems attributed to the hydrostatic balloon catheter were responsible for 2 failures. The regional anaesthetic technique failed to provide adequate anaesthesia for hydrodistension in 9 procedures and limited the duration to 2 h in 13 others. Following recall of the perished balloon catheters by the manufacturer, and the introduction of continuous spinal anaesthesia, the number of technical failures has been reduced. This technique still has an important role to play in the relief of severe symptoms unresponsive to medical treatment, but it is important that ideal conditions are provided for hydrodistension in order to ensure maximum success, particularly when the alternative is major surgery. PMID- 1450846 TI - Botulinum toxin in the treatment of chronic urinary retention in women. AB - Six women were identified as having difficulty in voiding or complete urinary retention due to abnormal myotonic-like electromyographic (EMG) activity in the striated muscle of the urethral sphincter. An attempt was made to improve voiding by injection of botulinum toxin into the striated sphincter muscle. Although 3 patients then developed transient stress incontinence, demonstrating that sufficient botulinum toxin had been given to cause sphincter weakness, no patient had significant symptomatic benefit. PMID- 1450847 TI - The open access Continence Resource Centre for Greater Glasgow Health Board. AB - The development of an open access Continence Resource Centre is described. The role of the Centre in helping the sufferers and carers is highlighted. The educational role exceeded expectations. The benefits of the centre in education, research and potential cost saving are discussed. The aims and achievements are in accord with the Department of Health document "An Agenda for Action on Continence". From its opening in August 1989 to the end of February 1992 the centre has served 8070 incontinent individuals and 4736 carers. At a cost of 44,000 pounds per annum this represents good value for money. PMID- 1450848 TI - Preliminary results of concurrent cisplatin and radiation therapy in locally advanced bladder cancer. AB - Between March 1981 and March 1990, 15 patients with locally advanced transitional cell carcinoma of the bladder were treated concurrently with cisplatin and radiotherapy. Treatment comprised a radiation dose of 40-50 Gy in 20-25 fractions over 4-5 weeks and intravenous infusion of cisplatin with hydration during days 1 5 and 22-26. The total scheduled dose of cisplatin was 200 mg. A complete response (CR) was seen in 3 patients (2 T2 tumours and 1 T3) and the other 12 were regarded as partial responders. Two of the 12 partial responders (1 T2 tumour and 1 T4) underwent cystectomy after treatment, but 9 patients (2 T2, 6 T3 and 1 T4) underwent only transurethral resection. The remaining patient (with a T4 tumour) died from systemic disease, further treatment not being possible because of unrelated heart failure. In 3 CR patients and 9 with a partial response (PR), bladder function was preserved and they have survived for a mean of 18.3 months (range 5-47) after therapy. Although 4 patients in this group had recurrent bladder tumours and 1 died from cancer in another part of the body, 7 have survived with normal bladder function and no recurrence. It is concluded that concurrent cisplatin and radiation therapy is a safe and viable regimen and may be considered as a means of preserving the bladder in patients with locally advanced transitional cell carcinoma. PMID- 1450849 TI - Cold sensation and bladder instability in patients with outflow obstruction due to benign prostatic hyperplasia. AB - A series of 73 patients with bladder outflow obstruction caused by benign prostatic hyperplasia underwent urodynamic investigation, including the cold water test. The presence of detrusor instability was associated with a higher urethral opening pressure, maximum detrusor pressure and detrusor pressure at maximum flow. Instability was more common and more pronounced in patients with a lack of cold sensation, but there were some patients who, whilst lacking cold sensation, still possessed the cold reflex. This suggests partial denervation of the bladder or some form of altered modulation of sensory activity within the spinal cord or central nervous system. On the other hand, some of the patients lacked cold sensation but showed a stable detrusor and a high maximum cystometric capacity. This leads to the conclusion that there are different mechanisms by which the bladder reacts to outflow obstruction. PMID- 1450850 TI - Is indoramin an effective alternative to prostatectomy? AB - Alpha-1-adrenergic antagonists are recommended for symptomatic treatment of patients awaiting prostatic surgery. Their efficacy has been confirmed in placebo controlled clinical trials, but to date no comparison of their effects with the results of subsequent prostatectomy has been made. Fifty-five patients awaiting prostatectomy were assessed (by symptom scores and peak urinary flow rates) prior to treatment, on indoramin 20 mg bd, and 2 months following prostatectomy. Side effects while taking indoramin were experienced by 36% of patients. Despite an overall improvement in mean symptom scores, 26% of patients with obstructive and 30% of those with irritative symptoms who were assessed while taking indoramin failed to experience any improvement. Of the 31 patients assessed while on indoramin and again following surgery, prostatectomy produced a greater symptomatic relief than indoramin. The increase in peak flow rate following prostatectomy was 11.7 ml/s compared with 3.2 ml/s on indoramin. However, 5 patients preferred to continue taking indoramin rather than proceeding to surgery. Indoramin is no substitute for prostatectomy. Although some patients might benefit from treatment while awaiting surgery, significant side effects may severely restrict its use for this purpose. The response to indoramin cannot be used as an accurate predictor of response to prostatectomy. PMID- 1450851 TI - Outcome and prognostic factors in patients with advanced prostate cancer and obstructive uropathy. AB - In a series of 51 patients with prostate cancer and obstructive uropathy, unilateral or bilateral obstruction was identified in 22 (43%) and 29 (57%) respectively. This included a non-functioning kidney in 12 patients. In 86% of patients the T category was advanced. Bone metastases were present in 36 cases (71%); 19 patients (37%) had chronic retention. All patients with metastatic disease underwent hormonal manipulation and 43 underwent transurethral resection of the prostate. External beam radiotherapy, percutaneous nephrostomy and ureteric reimplantation were performed in 4, 5 and 1 patient respectively. Actuarial survival of all 51 patients was 57 and 25% at 2 and 5 years. Presentation with bilateral or non-function did not predict a worse prognosis in comparison with patients with unilateral hydroureteronephrosis. Raised alkaline phosphatase and prostatic acid phosphatase were of no prognostic value, while creatinine reached marginal significance. A positive bone scan and raised urea were strongly predictive of a poor outlook. It was concluded that prostate cancer and obstructive uropathy should not uniformly imply a terminal event, and interventional therapy is justified with a 25% 5-year survival rate. PMID- 1450852 TI - Testicular denervation. A new surgical procedure for intractable testicular pain. AB - Chronic testicular pain has many different aetiologies. Identification and treatment of an underlying problem resolve the issue in most cases. However, a proportion of patients with chronic testicular pain have no demonstrable aetiological factor and pose a difficult treatment problem. All of these patients are initially treated by non-surgical measures. Various operations advocated in the literature for non-responders include epididymectomy, scrotal orchiectomy and inguinal orchiectomy, all of which have a significant failure rate. We describe a hitherto unreported operative procedure in a series of 4 patients, with immediate and lasting relief of their pain. PMID- 1450853 TI - Testicular prostheses: the patient's perception. AB - There is a paucity of data to determine if the insertion of a testicular prosthesis is effective in overcoming the psychological effects of an absent testis. A review of 25 patients who had had testicular prostheses showed a high overall level of satisfaction in the 19 patients who were traced. This satisfaction was subject to some qualification. PMID- 1450854 TI - In vitro investigations into the formation and dissolution of infection-induced catheter encrustations. AB - Encrustations are the most frequent complications occurring with indwelling catheters and urine drainage systems. The conditions for bacterial infections, using synthetic urine and controlled contamination by Proteus vulgaris, were standardised by using an in vitro model. Crystal deposits on catheters were analysed by infra-red spectroscopy and scanning electron microscopy. The main components of deposits in all investigations were struvite (MgNH4PO4.6H2O) 60-70% and carbonate apatite (Ca10(PO4,CO3)6 (OH,CO3)2) 30-40%. Investigations as to the quality and quantity of encrustations confirmed the analysis. Irrigation treatment was carried out with physiological saline solution and citric acid solution (Suby G) to study and quantify the dissolution of crystal deposits. Regular irrigation with citric solution resulted in a 70% dissolution of encrustations and ensured free flow as ascertained by measuring flow rates. PMID- 1450855 TI - Familial hollow visceral myopathy with varying urological manifestations. AB - A family with hereditary hollow visceral myopathy is described, with characteristic variation in expression between affected members. Very severe and widespread involvement of the gastrointestinal and urinary tracts in 1 patient contrasted with isolated urinary tract involvement in 2 others, and it is suggested that hollow visceral myopathy should be considered in the differential diagnosis of primary detrusor failure. The management of urinary tract involvement is discussed and a conservative approach is recommended. PMID- 1450856 TI - Endoscopic reappraisal of the morphology of congenital obstruction of the posterior urethra. AB - Congenital obstruction of the posterior urethra was first systematically classified by Young in 1919. Since then, no-one has seriously challenged the presence of both Type I and Type III "valves", although the presence of Type II lesions has often been disputed. A review of Young's papers and more recent anatomical studies, together with endoscopic findings in our own patients, indicates that most congenital posterior urethral obstructions are anatomically similar. Consequently, Young's classification now seems redundant. PMID- 1450857 TI - Paraplegia following spinal anaesthesia in a patient with prostatic metastases. PMID- 1450858 TI - Carcinoma in situ following tuberculous cystitis: an immunotherapeutic dilemma? PMID- 1450859 TI - Articular complications of intravesical BCG treatment for bladder carcinoma. PMID- 1450860 TI - Renal milk of calcium--a new contraindication to extracorporeal shock wave lithotripsy? PMID- 1450861 TI - Systemic candidiasis caused by a renal transplant ureteric stent. PMID- 1450862 TI - Profound haemorrhage causing acute obstruction in medullary sponge kidney. PMID- 1450863 TI - Urethro-vaso-cutaneous fistula: an unusual complication following bladder neck incision. PMID- 1450864 TI - Severe allergic reaction to an intraurethral preparation containing chlorhexidine. PMID- 1450865 TI - Upper quadrant end ureterostomy as urinary diversion for a solitary kidney in a case of extensive urothelial tumours. PMID- 1450866 TI - Endoscopic removal of non-deflating Foley balloon catheter. PMID- 1450867 TI - Simple technique for everting a spout ileostomy. PMID- 1450868 TI - Percutaneous dilatation of difficult nephrostomy tracts. PMID- 1450869 TI - Pre-vesical ureteric calculi: modified prone position for extracorporeal shock wave lithotripsy using the Siemens Lithostar. PMID- 1450870 TI - Epidemiology of the menopause. AB - Profound changes in birth and mortality rates in this century are resulting in the ageing of the population of Britain and other developed countries. The enormous decline in maternal mortality, in particular, has meant that increasing proportions of women are surviving to the menopause and years of active life beyond it. Women aged 55 years and over now comprise 15% of the population of Britain. The average life expectancy for women in developed countries is around 75 years; approximately 90% of women reach the age of 65 years, and 30% reach 80 years. If the average age of menopause is 50 years, most women will spend approximately one third of their lifetime in postmenopausal life; one in every two women will experience about 30 years of postmenopausal life. PMID- 1450871 TI - Endocrinological aspects of the menopause. AB - On average women live for about 30 years after the menopause. About 60-70% of consultations at the general practitioner and hospital specialist levels are for people over the age of 60, the majority of who are females. Therefore it is crucial to examine the effect of oestrogen prior to the menopause and how it interacts with other systems at cellular level. It is also important to examine why cells multiply and differentiate more efficiently in an oestrogenic milieu. This will give a better understanding of the degenerative processes of the menopause and will have profound implications on the design of effective hormone replacement therapy protocols. PMID- 1450872 TI - Hormone replacement therapy and cardiovascular disease. AB - Oestrogen alone probably confers a degree of protection against ischaemic heart disease and stroke and is appropriate for women requiring hormone replacement therapy (HRT) who have undergone hysterectomy. However, the cardiovascular effects of the progestogens used with oestrogen in the much larger number of women who have not undergone hysterectomy are unknown. Some widely used progestogens have adverse effects on lipoprotein levels and may raise blood pressure. The antithrombin III level may be involved in determining the response to oestrogen in different settings. The indications for HRT and the effects of different formulations on cardiovascular disease constitute one of the most pressing but complex issues in present-day medical practice. These questions can only be satisfactorily answered by the randomised controlled trials that should have been initiated several years ago and the feasibility of which is only now being investigated. PMID- 1450873 TI - HRT and osteoporosis. AB - Osteoporosis is characterised by low bone mass, leading to an increased risk of fragility fracture, particularly in the femoral neck, vertebrae and radius. These fractures constitute a major public health problem in the Western world; the estimated annual cost to the health services of hip fracture alone is over 500 million pounds in the United Kingdom. Using population-based data from the USA, Cummings et al. have estimated that the lifetime risks of hip, vertebral and Colles' fractures in a 50 year old, white, postmenopausal woman are 16%, 32% and 15% respectively. Of these, vertebral fractures probably cause the most significant morbidity, since they occur at a younger age than hip fractures and may result in pain, deformity and disability for many years until death intervenes from other causes. Hip fractures occur most commonly in the eight and ninth decades of life and have a mortality at six months of around 15%, increased dependency occurring in the majority of survivors. Colles' fractures, although not usually associated with long-term morbidity, nevertheless cause considerable inconvenience and require hospital treatment. PMID- 1450874 TI - Hormone replacement and cancer. AB - The increasing extended use of noncontraceptive oestrogen by postmenopausal women, intended to prevent other conditions, may at the same time increase their risk of reproductive cancer. The risk of endometrial cancer triples after only a few years of unopposed oestrogen, persists for many years after oestrogen has been discontinued, and appears to be preventable by the addition of a progestin. The effect of replacement hormones on the risk of breast or ovarian cancer is unknown. Most studies suggest a small but significant increased risk of breast cancer after long-term use. Awareness of the known and uncertain cancer risks should be included in decisions to use replacement hormones. PMID- 1450875 TI - Hormone replacement therapy and other menopause associated conditions. AB - In Britain a large majority of the women who use Hormone Replacement Therapy (HRT) use it in order to alleviate symptoms thought to relate to the menopause. These include vasomotor instability, 'minor' psychological disturbance and sexual difficulties. Other HRT effects gained by the women include effects on maintenance of collagen, as in the skin, and on oestrogen sensitive tissues related to the lower urinary tract. PMID- 1450876 TI - HRT: an analysis of benefits, risks and costs. AB - A cost-effectiveness analysis of hormone replacement therapy (HRT) was undertaken to assess the relative benefits of different treatment strategies, and to identify which factors most influence cost-effectiveness. The current lack of conclusive evidence on the effects of HRT, especially in relation to combined therapy and cardiovascular disease, necessitated the use of a large number of assumptions in our model. In terms of net health benefits, the potential reduction in cardiovascular disease would have greatest impact, and would overshadow any small increase in breast cancer risk possibly associated with long term use. Net expenditure by the NHS will depend critically on the direct costs of treatment, rather than on any indirect costs incurred or averted as a result of side-effects. In terms of cost-effectiveness, long-term prophylactic treatment of hysterectomised women and treatment of symptomatic women with a uterus compare favourably with other accepted health care interventions. PMID- 1450877 TI - HRT: developments in therapy. AB - Various forms of oestrogen have been available for use as Hormone Replacement Therapy (HRT) for approximately 50 years. However, there has been little change in the mode of administration until the last 10-15 years. Although the oral route has remained the mainstay of therapy, non-oral routes of administration have been developed. During the 1970s it became clear that use of unopposed oestrogens in women with an intact uterus resulted in an increase in risk of endometrial carcinoma and thus the current practice of adding a sequential progestogen each month, to prevent endometrial hyperplasia, was introduced. However, certain progestogens can cause side-effects and some of the metabolic changes which they induce are potentially undesirable. Thus the search continues for new oral progestogens which are more 'metabolically friendly' than those in current use. Additionally, non-oral delivery systems for progestogens have been studied, such as the transdermal route (patches) and local administration within the uterine cavity (progestogen-containing intra-uterine devices). Both these strategies may minimise their symptomatic, psychological and metabolic effects. Continuous (every day) administration of progestogens in combination with the oestrogen, or the use of new compounds (e.g. tibolone) may overcome the problem of regular withdrawal bleeding which some women find unacceptable. However, it remains to be determined whether such therapies are as efficacious as conventional oestrogen/sequential progesterone regimens. PMID- 1450878 TI - Management of the menopause. AB - The management of the peri- or postmenopausal patient, whether symptomatic or asymptomatic, involves a careful assessment of the problems and expectations of each patient and the matching of appropriate treatment to their needs. The effects of the menopause and its treatment on the patient's immediate and long term health must be taken into account. This may involve consideration of aspects of medical topics as diverse as gynaecological endocrinology, bone metabolism, oncology and cardiology. Although the benefits of oestrogen therapy are well established the response to therapy must be carefully monitored. Vigilance in the monitoring and seeking out of adverse effects both in individuals and populations must continue to ensure that any problems with this form of therapy are detected at the earliest possible stage. PMID- 1450879 TI - Future prospects for hormone replacement therapy. AB - To avoid the complication of osteoporosis, hormone replacement therapy (HRT) is now standard therapy in women with premature ovarian failure. The indications for HRT after the age of 50 are more controversial. There are strong indications from case-control studies that in N. America and Europe HRT protects against osteoporotic fracture, myocardial infarction and stroke; yet the evidence from case control studies is insufficiently precise to quantitate accurately the potential benefits that would accrue from its more widespread use. Clear guidelines also need to be established on the potential usefulness of selective prescribing of HRT using one or more screening procedures. The only effective way of achieving this and of quantitating the potential benefits of HRT with sufficient accuracy is by means of one or more randomized controlled trials. Future research will also address concerns such as the possible increase in the risk of breast cancer after 10 or more years of therapy. Critical to the more widespread acceptance of HRT may be the development of safe regimes which do not promote uterine bleeding as well as minimizing other unwanted side-effects. PMID- 1450880 TI - Hormone replacement therapy. Comments from the editor. PMID- 1450881 TI - Sport and the overtraining syndrome: immunological aspects. AB - Acute exercise of varying severity and corresponding levels of long term competition and training have been found to affect various components of the immune system including lymphocyte subsets, immunoglobulin levels, the mononuclear phagocytic system, polymorphonuclear leukocytes and cytokines, especially IL-1, IL-2, IL-6 and TNF. A tentative trend may be discerned whereby light to moderate exercise may increase immune responsiveness but high-level competition sport, especially if it involves extensive endurance training, may lead to a degree of immunosuppression. Such immune malfunction may be a component of the overtraining syndrome, in which recurrent infections during periods of maximum training or competition stress may form part of the syndrome. Evidence is presented that such overworked muscle may fail to supply adequate glutamine for normal lymphocyte function. Principles of an overtraining treatment strategy are suggested. PMID- 1450882 TI - Sudden cardiac death in athletes. AB - Sudden death in athletes is a rare but tragic occurrence. Congenital cardiovascular abnormalities, usually asymptomatic and often undiagnosed during life, are the main causes in young athletes. Hypertrophic cardiomyopathy and congenital coronary anomalies are the most commonly occurring disorders. Idiopathic concentric left ventricular hypertrophy (non-physiological), arrhythmogenic right ventricular dysplasia and Marfan's syndrome with aortic rupture have also been implicated. Rarer causes include mitral valve prolapse and myocarditis. Coronary atherosclerosis is the major cause in older, and occasionally in younger athletes. Those involved in the medical care of athletes should be aware of the potential causes of sudden death in these groups. Symptomatic athletes should be fully investigated. Screening programmes are probably not justified on a cost effective basis. PMID- 1450883 TI - Exercise, amenorrhoea and the skeleton. AB - One of the accepted benefits of regular exercise is the development of increased bone mineral density (BMD) and hence a skeleton more capable of withstanding the rigours of physical activity throughout life. However an apparent paradox is seen in the observed decrease in lumbar BMD in female athletes who experience menstrual disturbance and athletic amenorrhoea (AA). Despite high levels of activity these athletes suffer the consequences of hormonal deficiency and are at risk of not achieving peak BMD and experiencing further bone loss. It is increasingly evident however that exercise itself continues to exert a protective effect of maintaining BMD at skeletal sites under physical stress. The observed increase then of stress fractures at these sites in amenorrhoeic athletes remains unexplained. PMID- 1450884 TI - The growing child in sport. AB - An increasing number of children undergo intensive training routines and high level competition from an early age. Although physical training may foster health benefits, many are injured as a result of it. Carefully controlled studies on the effects of training routines from childhood are however lacking. This paper reviews some of the effects of training in young athletes, focusing on physical, cardiovascular and muscular effects, and sports injuries. Psychological effects of intensive sports participation are briefly considered. Measures should be taken to modify the present structure of competitive sport to avoid the possible deleterious effects of intensive physical activity on children. PMID- 1450885 TI - Aerobic exercise, anaerobic exercise and the lactate threshold. AB - All exercise draws first on intramuscular stores of ATP and creatine phosphate; initially these are replenished by anaerobic glycolysis. The lactic acid produced contributes to the rapid development of fatigue in high intensity exercise. Aerobic metabolism (at first mainly of glycogen, later increasingly of fat) is the principal route of ATP resynthesis in activities lasting longer than 2 min, but can only maintain work-rates about 1/4 of those possible in very brief bursts. Blood lactate rises at the higher aerobic work rates. 'Lactate threshold' (LT: approximately 2 mmol/l) is almost exactly the speed at which endurance races are won, and close to those apparently providing optimal aerobic training. This training, predominantly of muscle aerobic capacity, elevates LT more than maximum oxygen consumption. LT is not now thought to indicate oxygen-deprivation, but intracellular adjustments driving oxidative phosphorylation faster. Ventilatory breakpoints, formerly considered to indicate LT, correlate more closely with the accumulation of potassium than lactate. PMID- 1450886 TI - Strength of skeletal muscle and the effects of training. AB - The performance of any sporting activity involves a combination of skill and strength and it is very difficult to disentangle their separate contributions. The strength of an individual muscle depends on a number of factors. The major factor is the cross-sectional area of the muscle but others include the extent to which the muscle can be activated by voluntary effort, the overall length of the muscle and the position in which it is used, the fibre type composition and the velocity at which the movement takes place. Over a period of 2 to 3 months the major benefit of training is to improve the skill with which the training exercise is carried out. The effect is very specific so that there is considerable doubt as to whether weight training does anything other than train the athlete to lift weights. Increases in muscle size and strength in a healthy athlete occur relatively slowly and apart from the fact that high forces are required, little is known about the factors which stimulate growth. Accumulation of metabolites and damage to the muscle fibres are possible stimuli for growth but the prescription of optimal training regimes remains a matter of personal choice between the athlete and trainer rather than athlete and physiologist. PMID- 1450888 TI - Psychological stress, performance, and injury in sport. AB - This paper reviews the empirical literature on psychological stress in sport, and the effects that such stress may have upon performance, vulnerability to injury, and rehabilitation from injury. It also examines the strategies that sports performers could use to overcome these effects. The major sources of stress that have been reported by sports performers include fear of failure, concerns about social evaluation by others (particularly the coach), lack of readiness to perform, and loss of internal control over one's environment. Various models and theories of the effects of such stress upon performance and vulnerability to injury are reviewed, including multidimensional anxiety theory and a catastrophe model of anxiety and performance. The cognitive and physiological processes which are thought to underly these effects are also reviewed, together with the intervention strategies that are implied by these processes. Research on the psychological stress that appears to be experienced by performers when they are injured is very limited. However, that which is available suggests that many of the same psychological skills that are thought to enhance performance can also be used to reduce the risk of injury, and promote a speedy recovery from injury. These include goal-setting, imagery, self-talk, and relaxation skills. PMID- 1450887 TI - Food and drink in sport. AB - The nutrition and fluid requirements of a sportsperson should be tailored not only to the sport, with endurance being the most important variable, but also to the individual competitor and the physical environment at the time of the event. This applies especially to fluid intake. There is agreement that the proportion of carbohydrate in the diet should be high and that of fat low. The evidence for increased metabolic demands for vitamins and minerals (except possibly calcium and iron) in exercise is equivocal. Fluid is still the priority constituent that needs monitoring. PMID- 1450889 TI - Exercise in prevention of disease. AB - Measures to increase individual participation in adequate amounts of physical exercise have a key place among the strategies to improve health and prevent disease. The scientific justification is based on a variety of evidence drawn from numerous epidemiological, clinical and physiological studies and is accepted as sound. The prevalence of physical disability is high. Disability attributable to age or chronic disease is helped by exercise. Inactivity compounds the effects of disability--an effect which deserves recognition because it is reversible and not inevitable. The association between a high level of habitual physical activity and a reduction in the individual risk for coronary vessel disease (CVD) is real and appears to be causal. Regular vigorous aerobic exercise is certainly effective in maintenance of health. Weight-bearing exercise has been shown to prevent osteoporosis at any age. The links between many of the functional adaptations which occur with exercise and improvements in health have been demonstrated. The exercise programmes which are effective have been defined. PMID- 1450890 TI - Focal points in orthopaedics. AB - Orthopaedic surgeons have long had an association with sport, although it is arguable whether Galen who was the first sports medicine doctor, appointed to the Pergamum Gladiators in 157 AD was a surgeon by todays definition. This surgical role is now out of proportion to the more global aspects of sports medicine as reflected in the rest of this publication, but accurately related to the consequences of injury to the elite performer, where a minor injury may have a major consequence. As the title makes clear this chapter is a series of cameos some describing aspects of the management of common injuries and others indicating new developments. PMID- 1450891 TI - Exercise, injury and chronic inflammatory lesions. AB - The increasing frequency of injury over the last two decades reflects the activities of a more exercise conscious public. However, all too often injury may be due to ill-advised or inappropriate exercise and can be prevented by relatively simple modification of technique, equipment or gait abnormalities. Nevertheless, many injuries may simply reflect overtraining and the effects of repetitive strain on soft tissue and bony structures. This has led to an urgent need to understand better the mechanisms of injury, the importance of chronic inflammation and the factors involved in recovery of soft tissue strength. In the case of injuries to tendons or ligaments it is often difficult to define the contribution to symptomatology of collagen breakdown or chronic inflammation as a response to this. Furthermore, radiological changes at tendon and ligament attachments (entheses) through overuse can be indistinguishable from chronic inflammatory conditions such as spondarthritis, adding weight to the view that the body has a limited number of ways in which it can react to a variety of chronic stimuli. Marathon runners or footballers, for example, may develop symphysitis through chronic loading and radiologically there may be apparent erosive changes. Rheumatologists, dealing primarily with the chronic inflammatory arthritides, are beginning to understand better the factors involved in chronic inflammation and the effects of exercise. The Sports Physician must equally be aware of some of the pitfalls of misdiagnosis because of the masquerading of some primary inflammatory conditions as soft tissue injury or 'traumatic' joint effusion. This article will therefore review advances in current understanding of the influence of exercise on chronic inflammation and on recovery of tissue strength in sporting injuries. Improving understanding should lead to more defined rehabilitation programmes and a reduction in the all too common reinjury cycle. PMID- 1450892 TI - Gender verification testing in sport. AB - Gender verification testing in sport, first introduced in 1966 by the International Amateur Athletic Federation (IAAF) in response to fears that males with a physical advantage in terms of muscle mass and strength were cheating by masquerading as females in women's competition, has led to unfair disqualifications of women athletes and untold psychological harm. The discredited sex chromatin test, which identifies only the sex chromosome component of gender and is therefore misleading, was abandoned in 1991 by the IAAF in favour of medical checks for all athletes, women and men, which preclude the need for gender testing. But, women athletes will still be tested at the Olympic Games at Albertville and Barcelona using polymerase chain reaction (PCR) to amplify DNA sequences on the Y chromosome which identifies genetic sex only. Gender verification testing may in time be abolished when the sporting community are fully cognizant of its scientific and ethical implications. PMID- 1450893 TI - Pathophysiology of soft tissue repair. AB - Inflammation with subsequent migration of leucocytes and connective tissue cells to the site of damage, together with the release of cytokines by these cells are essential for healing in common sports injuries. Injury to the musculotendinous unit resulting from either blunt trauma, tears or laceration, heal primarily by formation of granulation tissue and scarring. Early diagnosis with appropriate therapy may minimize any potential loss of function. Ligament repair also follows a classical healing response, although the quality of healing is site dependent and may be related to exposure to synovial fluid. In contrast, cartilage, which is avascular, lacks the inflammatory response seen in other connective tissues and this frequently results in poor tissue repair with subsequent degeneration of the injured cartilage. Mechanisms of repair in these tissues are described. PMID- 1450894 TI - Morphology, behavior, and evolution: comparative kinematics of aquatic feeding in salamanders. AB - The kinematics of aquatic prey capture were studied in species representing six salamander families (Ambystomatidae, Amphiumidae, Cryptobranchidae, Dicamptodontidae, Proteidae, and Sirenidae) to test the hypothesis that the process of aquatic prey capture is similar in these families. Seven variables were digitized from high-speed video records of prey capture, and a nested analysis of variance was performed to test for both significant individual within taxon and among taxa effects. The time-to-peak head angle and gape variables showed no taxon effect, while the other five variables exhibited highly significant differences among taxa. Cryptobranchus and Siren showed the most divergent kinematic pattern from the other taxa in a multivariate analysis of all variables, while Ambystoma, Dicamptodon, and Amphiuma tended to have similar overall patterns of head movement. These results show that kinematic patterns during aquatic feeding are not conserved across salamander taxa, and that phylogenetic differentiation in head morphology has been accompanied by novelties in feeding function. The feeding mechanisms of Cryptobranchus and Amphiuma have a bidirectional hydrodynamic design with kinematic correlates that are similar to kinematic characteristics of aquatic feeding in turtles and transformed ambystomatid salamanders. A general framework is presented as an aid to understanding the interrelationships among muscle activity patterns, morphology, and behavior (kinematic patterns). By considering the distribution of taxa in three multivariate spaces, corresponding to three of the levels at which one might analyze a behavior (kinematics, morphology, and motor pattern), it is possible to identify patterns of correspondence among the levels, which aid in understanding the evolution of behavior. PMID- 1450895 TI - Changes in retinal projections and ganglion cell morphology after unilateral enucleation in the common carp. AB - Changes in retinal projections and ganglion cell morphology were studied in one eyed individuals of the common carp, Cyprinus carpio, which were enucleated at a juvenile stage (within 6 months after hatching) and kept for 18 months after the operation. Gross examination of the brains showed a marked atrophy of the contralateral optic tectum and a fine attenuated optic tract ipsilateral to the remaining eye. All retinal recipient areas were bilateral, but numerous projections were heavier contralaterally. Terminal branches in the recipient areas showed more complex patterns with tortuous courses and larger numbers of terminal swellings than in normal animals. Total numbers and distribution patterns of ganglion cells in Nissl-stained retinal whole mounts of one-eyed carp were compared with those in normal carp. The total number of ganglion cells was estimated to be 14 x 10(4)-18 x 10(4) in both one-eyed and normal carp. No difference was observed in isodensity maps and soma area histograms between one eyed and normal carp. Following injections of horseradish peroxidase and nuclear yellow into the optic tectum of each side, three different types of tectal projecting ganglion cells were observed in the remaining retina: contralaterally projecting (CP) cells, ipsilaterally projecting (IP) cells, and bilaterally projecting (BP) cells. The distribution pattern of CP and BP cells in the retina suggested normal retinotopy. However, BP cells were found in a more restricted zone within the CP cell distribution area. The IP cells had a tendency to be scattered sparsely in a wide central area and a dorsal quadrant of the retina. No IP or BP cells were found in the peripheral retina. The time course and morphological changes in axons of these cells are discussed. PMID- 1450896 TI - Physiological characterization of lateral line function in the Antarctic fish Trematomus bernacchii. AB - The Antarctic notothenioids are a monophyletic radiation of fishes that have evolved under conditions of low light and cold, where non-visual sensory systems, such as the mechanosensory lateral line system, would be of importance. As part of a study of the structure and function of the mechanosensory lateral line system in these fishes we systematically characterized the function of the anterior lateral line system in one of the common benthic species, Trematomus bernacchii. Frequency-response and threshold-tuning curve methods yield similar functional characterizations of single afferent fibre responses to vibrational stimulation. Curve fitting of generalized transfer function to frequency-response curves allows an objective splitting of responses into velocity and acceleration sensitive populations thought to correspond to superficial and canal neuromasts, respectively. Both response types are characterized by a low-pass frequency response curve, with a relatively low upper frequency cut-off when compared with data from temperate species. The sensitivity of the lateral line system of T. bernacchii is comparable to that of the mottled sculpin Cottus bairdi. PMID- 1450897 TI - Fibers innervating different parts of the lateral line system of an Antarctic notothenioid, Trematomus bernacchii, have similar frequency responses, despite large variation in the peripheral morphology. AB - Regional differences in the architecture and size of lateral line canals and neuromasts were measured in an Antarctic fish, Trematomus bernacchii, and the data were used in models of canal and cupular mechanics to predict the frequency response of these two peripheral structures. These modeled predictions were then compared to frequency response functions measured with single unit recording techniques from anterior and posterior lateral line fibers innervating different canals on the head and trunk of fish of various sizes. Despite large variations in the peripheral morphology of head and trunk canals in fish of different sizes, lateral line fibers were relatively homogeneous in their frequency response properties. In response to stimuli of equal pk-pk acceleration levels, all canal neuromast fibers responded with equal and maximum responsiveness in the 10-45 Hz range, after which responsiveness fell off at about 18 dB/octave. Whereas the biomechanical models of cupular and canal responsiveness predicted the region of equal and maximum responsiveness in the 10-45 Hz range, they did not predict the high frequency cutoff nor the slope. Rather, these models predicted responsiveness out to at least 540 Hz, and a high frequency slope of 12 dB/octave. In terms of the frequency response of peripheral fibers, we conclude that (1) there can be considerable morphological variability, with little consequence for function, as long as some minimum standards for maintaining constant acceleration responsiveness in the 10-45 Hz range are met, and (2) there must be additional filters between the cupula and primary afferent fibers. PMID- 1450898 TI - Immunohistochemical study of the development of serotoninergic neurons in the brain of the brook trout Salvelinus fontinalis. AB - Serotonin is believed to play an important role in the neuronal development of various invertebrates and mammals, but only one study has yet investigated the development of serotoninergic neurons in the brain of a teleost. In the present study, we investigate the development of serotoninergic neurons in the brain of the brook trout, Salvelinus fontinalis, by immunohistochemistry, from fertilisation to the resorption of the yolk sac and in juveniles for reference. Maintaining trout embryos and larvae in 9L:15D or in complete darkness made no difference in the appearance and distribution of serotonin immunoreactive (5 HTir) neurons. On day 56, the first 5-HTir perikarya, indicative of the primordia of the nuclei raphe medialis/dorsalis, have stained in the presumptive isthmus region. At hatching time (days 95-115), all the 5-HTir nuclei reported in the juvenile are present, except for the population observed in the lobus inferior hypothalami. We observed that the nucleus recessus lateralis stained on day 58, the raphe caudal nucleus on day 60, the nuclei raphe pallidus and obscurus on day 65, the area praetectalis on day 80, and the nucleus recessus posterioris and the anterior group of the nucleus recessus lateralis on day 92. At the complete resorption of the yolk sac (days 175-190), the nucleus reticularis paragigantocellularis, the nuclei raphe pallidus and obscurus and the caudal raphe of the brainstem are very weakly immunoreactive, and in juveniles, only one caudal immunoreactive nucleus is still present. A comparison of our result with those previously reported in the three-spined stickleback, Gasterosteus aculeatus, suggest a similar distribution of 5-HTir neurons in the brain of both species but also reveal species differences in the sequence of appearance of 5HT immunoreactivity in the different neuronal populations. PMID- 1450899 TI - Quantitative histological study of the optic nerve in species of minnows (Cyprinidae, Teleostei) inhabiting clear and turbid water. AB - Quantitative analysis of the optic nerve of minnows using light- and electron microscopy demonstrated that anatomical characteristics of the visual system are closely related to habitat turbidity. Species in the genera Notropis and Cyprinella inhabiting predominantly clear water had larger eyes and almost twice as many optic nerve fibers compared to minnows of turbid habitats. No differences were detected in the thickness of myelination, the axon diameter profile, or the number of optic nerve fibers per retinal area, indicating that the relative number of fibers, as well as their anatomical characteristics, are similar in all species and independent of habitat turbidity. It is therefore hypothesized that quantitative differences in the number of visual elements available for sampling and processing in the retina, optic nerve, and optic tectum are sufficient to account for presumed differences in visual performance. PMID- 1450900 TI - Variation of tectal morphology in teleost fishes. AB - The morphological organization of the optic tectum was analyzed in a number of divergent teleost species. Particular attention was focused on the organization of the periventricular gray zone and of afferent and efferent fiber systems within or adjacent to it. A dorsal part of the periventricular gray zone is recognized which is in register with the distribution of tangentially and radially oriented fascicles. A lateral part of the periventricular gray can be identified as being lateral to the lateral-most of the tangentially and radially oriented fascicles and being in register with a large number of circular fascicles in the deep white zone. Circular fascicles pass between the lateral part of the periventricular gray and a more ventral part. There are few if any circular fascicles in the part of the deep white zone that is in register with the ventral part of the gray. These parts of the periventricular gray are most clearly apparent in clupeomorph fishes, due to an exaggerated separation related to the presence of two tectal lobes within the hemisphere. It is hypothesized that the dorsal part of the gray, as can be recognized cytoarchitectonically, is in register with the projection of the dorsal optic tract and that the lateral and ventral parts of the gray are in register with the projection of the ventral optic tract. PMID- 1450901 TI - Characteristics of saccades induced by neck torsions: a re-examination in the normal guinea pig. AB - Torsion of the neck relative to the fixed head results in several reflexes involving the eyes, the neck and the body. One of these reflexes, the cervico ocular reflex, has been described as having a small gain in the normal animal. However, when the body of a guinea pig is moved relative to the fixed head with a ramp-like velocity profile, saccades are systematically elicited in the direction of body movement. We re-examined the characteristics of this reflex in the normal guinea pig and demonstrated that: (1) it occurs mainly in the range of high velocity body movements; (2) the latency of the saccades is shorter than previously suspected; (3) the saccades are triggered at specific positions relative to the starting and ending positions of rotation, revealing some degree of flexibility in the reflex. We hypothesize that these saccades of nuchal origin are under the control of the same neuronal circuit as visually triggered saccades and quick phases of vestibular nystagmus. Thus, this nuchal reflex may fundamentally subserve orienting behaviour in normal animal. PMID- 1450902 TI - Paradoxical analgesia produced by naloxone in diabetic mice is attributable to supersensitivity of delta-opioid receptors. AB - The effects of naloxone on the analgesic response were examined using the tail flick test, in mice with streptozotocin-induced diabetes. Subcutaneous injection of naloxone (5 mg/kg, s.c.) produced a marked analgesia in diabetic mice but not in age-matched non-diabetic mice. Naloxone-induced analgesia in diabetic mice was significantly reduced by pretreatment with naltrindole (0.1 mg/kg, s.c.), a selective antagonist of delta-opioid receptors. By contrast, no significant naloxone-induced increase in tail-flick latency in diabetic mice was observed after chronic treatment with naloxone (5 mg/kg, s.c.) for 5 days. However, the tail-flick latency was significantly increased by chronic treatment with naloxone in non-diabetic mice. Furthermore, the significant naloxone-induced increase in tail-flick latency in non-diabetic mice that had been chronically treated with naloxone was also antagonized by pretreatment with naltrindole. Chronic pretreatment with 5 mg/kg of naloxone for 5 days markedly attenuated the analgesic effect of the delta-agonist DPDPE in diabetic mice, whereas this pretreatment significantly enhanced the effect of DPDPE in non-diabetic mice. These results suggest that naloxone-induced 'paradoxical' analgesia in mice may be mediated predominantly by delta-opioid receptors. PMID- 1450903 TI - Effect of amygdaloid kindling on [3H]dopamine and [14C]acetylcholine release from rat prefrontal cortex and striatal slices. AB - The involvement of the dopaminergic (DA) systems in the control of limbic kindled seizures is ill defined. The effects of kindling on DA activity may have been overlooked in the past, because of its subtle unilateral occurrence and/or the variance of the endogenous imbalance of DA activity in normal animals. In the present study rats were screened for their endogenous DA imbalance using amphetamine-induced rotational behaviour. Electrical or sham kindling was applied in the hemisphere with the higher endogenous DA activity. Sections of the bilateral prefrontal cortex and dorsal and ventral striatum were dissected either 2 hours or 21 days after the final seizure and the electrically stimulated release of [3H]DA and [14C]acetylcholine (ACh) determined. Release was also measured in the presence of quinpirole or sulpiride to assess the activity of pre and postsynaptic DA D2-receptors. Long-term effects of kindling consisted of facilitation of ACh release in the ventral striatum contralateral to the kindled amygdala and bilateral depression of DA release in the prefrontal cortex. Kindling therefore produced area specific changes in neurotransmitter systems giving rise to increased pro-convulsive cholinergic activity in the ventral striatum and decreased anti-convulsive dopaminergic activity in the prefrontal cortex. PMID- 1450904 TI - Neural sensitivity to pentylenetetrazol convulsions in inbred and selectively bred mice. AB - In these experiments, sensitivity to the convulsant drug pentylenetetrazol (PTZ) was measured in 10 inbred mouse strains, and in 4 mouse lines selectively bred for severe (WSP1, WSP2) or minimal (WSR1, WSR2) ethanol withdrawal convulsions. Using a timed infusion procedure, sensitivity to convulsions was assessed by measures of latency to convulsion, effective dose (ED) infused at time of convulsion, and brain concentration (BC) of PTZ at time of convulsion. In addition, ED and latency to convulsion were measured in WSP and WSR mice at 5 different concentrations of PTZ. Higher concentrations, which increased rate of drug infusion, reduced latency but had little effect on ED. WSP1 mice were slightly more sensitive to PTZ than WSR1 mice, but WSP2 mice were equally or less sensitive than WSR2 mice. Among the inbred strains, latency, ED and brain PTZ concentration were found to be highly correlated, suggesting that pharmacokinetic factors do not significantly influence access of PTZ to sites of action in the central nervous system. The C57BL/6J strain was least sensitive by all measures, while DBA/2J mice were highly sensitive. The BALB/cJ strain was the most sensitive strain as assessed by ED and latency, but BC indicated relatively average sensitivity. Apparently, pharmacokinetic factors in this strain result in a relatively rapid accumulation of drug in brain, making it appear to be more sensitive. Thus, although ED provides a reliable estimate of neural sensitivity in general, genetic factors exist which, in some strains, modify access of PTZ and possibly other drugs to brain, potentially affecting determination of sensitivity in the absence of a measure of brain drug concentration. PMID- 1450905 TI - Impaired learning and memory in mature spontaneously hypertensive rats. AB - In very old, normotensive rats, a disorganization occurs selectively in the retrosplenial cortex, and a similar disorganization occurs in this area in spontaneously hypertensive rats (SHR) at a much earlier age. Since this breakdown compromises a neural circuit involved in learning and memory, this study tests the hypotheses that these functions are disturbed in mature SHR and that they can be prevented or attenuated by long-term, anti-hypertensive therapy. SHR and Sprague Dawley rats (SD) at 3- and 12 months of age, and a group of SHR that had been normotensive from 3 to 12 months of age (CAP-SHR) were trained on an 8 arm radial maze task. Of the 12-month-old groups, SD reached criterion earliest (28 +/- 2 days) and made the least number of total errors. In comparison, 12-month old SHR took significantly longer to reach criterion (39 +/- 2 days) and made nearly twice as many total errors. CAP-SHR were intermediate between the other two groups (32 +/- 2 days). Three-month-old SD learned the task at the same rate as the 12-month-old SD. In contrast, 3-month-old SHR learned the task significantly faster (21 +/- 1 days) and with fewer errors than any other group. These data indicate that, in SHR, learning and memory are compromised by 12 months of age, and that anti-hypertensive therapy with captopril partially prevents this decline. PMID- 1450906 TI - Influence of medial septal cholinoceptive cells on c-Fos-like proteins induced by soman. AB - The effects of intraseptal application of atropine on c-fos proto-oncogene expression related to soman treatment were studied by immunohistochemistry for c Fos-like proteins. In control rats, 2 h after the onset of convulsion, c-Fos-like immunoreactivity was intense in the piriform and entorhinal cortices, but also in the cingulate, frontoparietal and retrosplenial cortices. In addition, the staining was moderate in the hypothalamus, amygdala and fascia dentata. The intraseptal application of atropine, which prevented soman-induced convulsions, reduced or even blocked c-Fos-like protein production related to soman treatment. This inhibition of Fos induction was significant in most of the limbic structures but also in non-limbic areas. The data in this study strongly suggest that the cholinergic cells of the medial septal area play a key role in soman-induced seizures, and confirm that c-Fos-like protein induction is closely related to neuronal hyperactivity. PMID- 1450907 TI - Perinatal hypoxic ischemic encephalopathy affects the proportion of GABA immunoreactive neurons in the cerebral cortex of the rat. AB - The hypothesis was tested whether perinatal hypoxic ischemia leads to a preferential degeneration of the GABAergic inhibitory neurons in the cerebral cortex which, in turn, could account for the reported higher risk of developing epilepsy later in life. To that end rat pups, aged 12-13 days, were made hypoxic by employing a combination of unilateral ligation of one of the carotid arteries and a 90-min exposure to 8% O2. After recovery periods of 3, 7, 35 and 150 days, the animals were sacrificed by perfusion fixation and the brains embedded in Epon. Transverse semi-thin sections were alternately stained with an antibody against GABA and with Toluidine blue. By using an unbiased morphometric method (the disector) the number of GABA-immunoreactive (GABA-IR) neurons and the total number of nerve cells per unit volume of tissue were estimated in corresponding neocortical areas in the ipsilateral (damaged) and contralateral ('control') hemisphere. For all animals with post-ischemic survival times of 3 and 7 days GABA-IR cells constituted a lower proportion of the total number of nerve cells in the damaged than in the 'control' cortical areas. This finding was consistent with the outcome of an earlier in vitro study. By contrast, in all animals with a survival time of 35 and 150 days, the proportion of GABA-IR neurons was higher on the damaged than on the 'control' side. This switch in the direction of the left/right differences, apparently depending on the length of the post-ischemic survival time, was statistically significant. No lateralization in the proportion of GABA-IR cells was detected in the cerebral cortex of the control rats. These observations, therefore, do not support the hypothesis that perinatal hypoxic ischemia ultimately leads to a preferential loss of GABAergic neurons in the cerebral cortex. PMID- 1450908 TI - Gravitoinertial force level affects the appreciation of limb position during muscle vibration. AB - Illusory motion and displacement of the restrained forearm can be elicited by vibrating the biceps brachii or triceps brachii muscle. We measured the influence of gravitoinertial force level on these perceptual responses to vibration during parabolic flight maneuvers where normal (1G) and high force (1.8G) background levels alternated with microgravity (0G). Subjects indicated the apparent forearm position of the vibrated arm with the other forearm and also made verbal reports. Biceps brachii vibration induced illusory extension of the forearm and triceps brachii, illusory flexion; these apparent motions and displacements were highly G force-dependent being enhanced at 1.8G and diminished at 0G relative to normal 1G force level. These alterations are discussed in terms of vestibulo-spinal and propriospinal influences on alpha-gamma motoneuronal control of muscle tone and the varying requirements for postural load support in different force backgrounds. Their implications for the control and appreciation of limb movements during exposure to different G force levels are also described. PMID- 1450909 TI - Lesions of the nucleus paragigantocellularis alter ex copula penile reflexes. AB - The effects of electrolytic lesions of the rostral nucleus paragigantocellularis (nPGi) were examined on ex copula sexual reflexes in male rats. Bilateral lesions of the nPGi significantly reduced (by 50%) the onset of the first ex copula reflex, which usually was a glans erection. In addition, the number of dorsiflexions (flips) was significantly increased. In the anesthetized spinally intact rat the urethrogenital reflex cannot be evoked. However, after chronic bilateral lesions of the rostral nPGi, half of the rats tested displayed the urethrogenital reflex prior to section of the spinal cord. These data support a role for the rostral nPGi in the descending inhibition of male sexual reflexes. PMID- 1450910 TI - Histamine H1 receptors in UC-11MG astrocytes and their regulation of cytoplasmic Ca2+. AB - Experiments were carried out on UC-11MG human astrocytoma cells, a continuous cell line that expresses a broad range of the biochemical and electrophysiological properties found in well-differentiated astrocytes. Because of a number of recent reports that astrocytes may express receptors for a variety of neuro-active substances, we measured the effects of 12 different neurotransmitters on intracellular free Ca2+ (Ca2+i) in UC-11MG cells. Of these neurotransmitters only histamine was found to have a significant effect. Further characterization of the nature of the histamine response showed that UC-11MG cells express mepyramine-sensitive H1 receptors the activation of which causes both mobilization of Ca2+ from intracellular stores and entry of Ca2+ from the extracellular solution. No evidence was found for the presence of H2 receptors. The Ca2+i response was maximal at 300 microM histamine and was attenuated by increasing cell density. We suggest that this neurotransmitter may play a role in astrocytic function in the human CNS. PMID- 1450911 TI - Histamine stimulates glycogenolysis in human astrocytoma cells by increasing intracellular free calcium. AB - Astrocytes from a variety of sources, including the human UC-11MG astrocytoma line, express receptors for histamine on their plasma membranes, but the function of these receptors is largely unknown. Here we report studies on the effect of histamine on newly synthesized glycogen in the human astrocytoma-derived cell line, UC-11MG. We have found [3H]glycogen hydrolysis with a EC50 of 2 microM and a maximum effect of 30% at 300 microM histamine. The glycogenolytic effect of histamine was completely blocked by the H1 receptor antagonist, mepyramine, and was insensitive to the H2 receptor antagonist, cimetidine. Histamine-induced glycogenolysis was significantly reduced in the absence of extracellular Ca2+ and the residual response could be accounted for by Ca2+ released from intracellular stores. The Ca2+ ionophore, ionomycin, induced a similar concentration-dependent increase in both intracellular Ca2+ concentration and in glycogenolysis. These results suggest that one function of astrocytic histamine receptors in vivo may be the stimulation of glucose release from astrocytes, and that this process is mediated by increased intracellular free Ca2+. The glycogenolytic effect of histamine and other neurotransmitters in different systems, and the possible implication of astrocytic glycogenolysis in the pathophysiology of ischemia are discussed. PMID- 1450912 TI - The striatopallidal projection displays a high degree of anatomical specificity in the primate. AB - The striatopallidal projection in the squirrel monkey (Saimiri sciureus) was studied with two highly sensitive anterograde tracers, the lectin Phaseolus vulgaris leucoagglutinin (PHA-L) and biocytin. After small PHA-L injections into various sectors of the striatum, the striatopallidal projection was found to display a very precise topographical organization. Fibers from the head of the caudate nucleus emerge as several distinct fascicles that penetrate the dorsal portion of the pallidum at various points along its rostrocaudal extent. Each fascicle arborizes into the dorsal third of the pallidum as dense plexuses composed of numerous fibers that closely entwined the dendrites of pallidal neurons, hence forming typical 'woolly' fiber arrangements. In contrast, fibers from the postcommissural putamen emerge as a few compact bundles that reach the pallidum through its lateral surface. In the pallidum, thin fibers detach themselves from these compact bundles, sweep caudally, and arborize in the form of narrow and elongated bands aligned parallel to the medullary laminae. Each band appears composed of numerous, thin and weakly varicose fibers that make only en passant type of contact with pallidal cell bodies rostrally, but form a dense field of woolly fibers caudally. In cases in which two PHA-L injections were made at two different rostrocaudal levels in the putamen, two rostrocaudally distant fields of woolly fibers, separated one another by thin varicose fibers, occur in each band. Furthermore, each PHA-L injection site in the striatum gives rise to at least two bands in each pallidal segment, indicating that the primate striatum has a dual representation at pallidal level. Finally, injections of PHA-L and biocytin into two small and mediolaterally adjacent areas of the postcommissural putamen lead to the formation of two clearly distinguishable sets of bands in each pallidal segment. Even though they lie very close to one another these two types of bands never really overlap. This experiment shows that, in contrast to previous beliefs, axons of striatal neurons from two small adjacent populations do not converge upon the same pallidal neurons but instead project to several distinct subsets of pallidal neurons. The findings of the present study reveal that the striatopallidal projection system in primates is highly ordered and displays a high degree of specificity with respect to its target sites in the pallidum. Different anatomical strategies are used to maximally exploit the relatively small pallidal space and ensure that the finely tuned corticostriatal information is not blurred as it flows through the funnel-shaped pallidum. PMID- 1450913 TI - Nerve growth factor effects on pyridine nucleotides after oxidant injury of rat pheochromocytoma cells. AB - Neurotrophic factors regulate neuronal survival and neurite growth in development and following injury. Oxidative stress produced in neurons as a consequence of primary injury, or during reperfusion following ischemia, may contribute to cell death. Here, the effects of nerve growth factor (NGF) on the response to H2O2 injury were examined in the PC12 rat pheochromocytoma cell line. Specifically, the effect of NGF on cell viability after H2O2 injury was measured. Pretreatment with NGF enhanced survival after H2O2 treatment, as measured by Trypan blue dye exclusion, radiolabeled amino acid incorporation, tetrazolium salt reduction, or cytoplasmic enzyme release. One early event associated with H2O2 treatment was a rapid decrease in NAD+. Although initial decreases in NAD+ levels were similar in control and NGF-treated cells, the latter recovered more rapidly and extensively. The decline in total NAD observed after NGF treatment was almost equal in magnitude to the measured increase in NADP. Inhibition of poly(ADP-ribose) polymerase also enhanced viability following H2O2 injury. Treatment with both NGF and an inhibitor of this enzyme resulted in a greater reduction of H2O2 toxicity than was observed with either agent alone. These data suggest that NGF protection is multifactorial and that a significant component of the NGF effect is due to its regulatory role in the metabolism of pyridine nucleotides. PMID- 1450915 TI - Morphology of central terminations of intra-axonally stained, low-threshold mechanoreceptive primary afferent fibers from oral mucosa and periodontium in the rat. AB - Horseradish peroxidase (HRP) was injected intra-axonally into functionally identified primary afferent fibers within the rat spinal trigeminal tract in order to study the morphology of their central terminations. They were physiologically determined to be large, myelinated afferent fibers from periodontium or oral mucosa by means of electrical and mechanical stimulation of their receptive fields. Twenty-eight axons that innervated the periodontium of incisors and 21 axons that innervated the oral mucosa were stained for distances of 2-5 mm from the injection sites at the levels of the main sensory nucleus (Vms), spinal trigeminal nucleus and rostral cervical spinal cord. The collaterals of these primary afferent fibers formed terminal arbors in the medial or dorsomedial part of the Vms, and the oral and interpolar spinal trigeminal nuclei (Vo and Vi). In the caudal spinal trigeminal nucleus (Vc), the collaterals of one half of the periodontium afferent fibers terminated mainly in lamina V at the rostral and middle levels of Vc. On the other hand, the collaterals of the other half of the periodontium afferent fibers terminated mainly in lamina IV at the rostral level of Vc, and rostrally these terminal areas shifted to the most medial part of Vi. The collaterals of mucosa afferent fibers terminated in lamina V at the rostral level of Vc, and these terminal areas shifted gradually to laminae III and IV as the parent axons traveled more caudally. These shifts were staggered rostrocaudally according to the rostrocaudal locations of the receptive fields. The density of collaterals of periodontium afferent fibers in Vi was significantly larger than that of mucosa afferent fibers. The average size of the varicosities of periodontium afferent fibers was significantly larger than those of mucosa afferent fibers in Vo, Vi and Vc. The average number of varicosities belonging to single collaterals of slowly-adapting periodontium afferent fibers in Vi were significantly larger than those in Vo. In Vi, the average number of varicosities of single collaterals of slowly-adapting periodontium afferent fibers were significantly larger than those of rapidly-adapting periodontium afferent fibers. PMID- 1450914 TI - Central carbachol stimulates vasopressin release into interstitial fluid adjacent to the paraventricular nucleus. AB - We have used an in vivo double microdialysis probe technique in conscious rats to determine whether the application of carbachol to one paraventricular nucleus (PVN) can result in increased local release of vasopressin from that PVN. Experiments were carried out 24 h after placement of microdialysis probes lateral to each PVN. When both probes were perfused initially with 0.9% NaCl, vasopressin was detected in the outflow (dialysate) from both probes. When carbachol (100 micrograms/ml) was included in the perfusate of one probe for the first 10 min of a 30-min collection period, while the other probe continued to be perfused with saline alone, there was a seven-fold increase in the concentration of vasopressin in the dialysate from the carbachol-perfused probe; the vasopressin concentration in the dialysate from the contralateral probe increased only slightly. The plasma vasopressin concentration was also elevated. When one of the paired probes was perfused with carbachol (100 micrograms/ml) for 30 min, there were similar increases in the concentration of vasopressin in the dialysate from both probes and a sustained increase in the plasma vasopressin concentration. Thus, vasopressin is released into the interstitial fluid adjacent to the PVN under basal conditions, and this release can be substantially increased when vasopressin secretion to the periphery is stimulated. PMID- 1450916 TI - 5-HT3 receptor antagonists fail to block the suppressant effect of cocaine on the firing rate of A10 dopamine neurons in the rat. AB - In the present study, we have shown that cocaine is significantly more potent in suppressing the firing rate of dopamine cells in the ventral tegmental area (VTA or A10) than in the substantia nigra pars compacta (SNC or A9). We have also determined the ability of several 5-HT3 receptor antagonists to alter the electrophysiological response of A10 dopamine neurons in the rat to cocaine, as these compounds have been implicated in modulating the effects of drugs of abuse on the dopamine system. It was found that the 5-HT3 receptor antagonists ICS205 930, zacopride and ondansetron do not alter either the firing rate or cocaine induced suppression of the basal firing rate of A10 dopamine cells. PMID- 1450917 TI - Involvement of nucleus accumbens dopamine in the motor activity induced by periodic food presentation: a microdialysis and behavioral study. AB - Two experiments were undertaken to investigate the role of accumbens dopamine (DA) in food-related motor activities. Although presentation of large amounts of food elicits feeding behavior, periodic food presentation (PFP; e.g. a 45-mg pellet every 45 s) induces considerable locomotion, rearing and other motor activities in food-deprived rats. In the first experiment, in vivo microdialysis methods were used to study DA release and metabolism in the nucleus accumbens of behaving rats exposed to periodic food presentation. Four behavioral conditions were used: high rate of PFP (one pellet per 45 s), low rate of PFP (one pellet per 4 min), massed food presentation and food deprivation control. The rats that received a high rate of PFP showed substantial increases in locomotor activity, and also showed significant increases in extracellular DA and DA metabolites. Rats that received massed presentation of food pellets consumed large quantities of food, but showed no significant increases in locomotor activity or DA release. Although the group that received the high rate of PFP showed the highest motor activity and the largest increase in DA release, there was only a modest correlation (r = 0.34) between motor activity and increased DA release. In the second experiment, the neurotoxic agent 6-hydroxydopamine (6-OHDA) was injected into the nucleus accumbens in order to assess the effects of DA depletion of PFP induced motor activity. DA depletion significantly reduced PFP-induced motor activity in the first week after surgery, but by the second week DA-depleted rats had recovered normal levels of motor activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450918 TI - Low concentrations of penicillin partially suppress CA3 hippocampal IPSPs in vitro. AB - Low concentrations of penicillin (50-300 IU/ml) produce a pro-convulsant state in CA3 hippocampus characterized by low amplitude, low frequency (2-3 Hz) spontaneous field potential oscillations. Evoked field potentials were used to demonstrate that this distinct, coordinated behavior of the hippocampal neuronal network which is intermediate between normal activity and fully synchronized epileptiform bursting is the result of partial blockade of GABAA-mediated IPSPs. A new method for estimating the degree of IPSP block relative to convulsant doses of penicillin (2,000 IU/ml) indicates that the half-maximal effect occurs at 300 IU/ml. Fully synchronized bursts may require almost complete IPSP block. PMID- 1450919 TI - A single restraint stress exposure potentiates analgesia induced by intrathecally administered DAGO. AB - In rats, restraint exposure potentiates the magnitude and duration of analgesia following both the peripheral and intracerebroventricular administration of several opioid agonists as compared to non-stressed controls. It has been suggested that the site of action whereby restraint leads to potentiated opioid analgesia is located supraspinally. However, the possible contribution of spinal analgesic mechanisms also warrants investigation. Thus, the purpose of the present study was two-fold: (1) to determine whether a single exposure to restraint stress would result in the dose-dependent potentiation of analgesia following the intrathecal (i.t.) administration of the mu (mu)-receptor selective opioid agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) and (2) to quantify the degree of analgesia in restrained vs. non-restrained rats using the tail flick and hot-plate analgesic assays. Using rats implanted with chronic i.t. cannula, dose- and time-course curves were observed following the i.t. administration of DAGO. The results demonstrate that both the duration and magnitude of analgesia was significantly potentiated in restrained rats compared to non-restrained controls. Restraint-treated rats receiving 0.15-0.6 micrograms of DAGO i.t. showed 1.3-1.5-fold potentiation of analgesia in the tail-flick assay and a 2.3-5.6-fold potentiation using the hot-plate assay. Restraint immobilization potentiated the magnitude and duration of DAGO-induced analgesia administered by the i.t. route as measured by the tail-flick and hot-plate assays. These data suggest that spinal analgesic mechanisms significantly contribute to the enhanced analgesic potency of opioids in subjects exposed to restraint stress. PMID- 1450920 TI - Nitric oxide modulates NMDA-induced increases in intracellular Ca2+ in cultured rat forebrain neurons. AB - We studied the effects of nitric oxide (NO) and the NO-releasing agents sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP) and isosorbide dinitrate (ISDN) on N-methyl-D-aspartate (NMDA)-induced increases in intracellular Ca2+ ([Ca2+]i), whole-cell patch-clamp currents and on glutamate stimulated [3H]dizocilpine binding. NO and agents that release NO partially inhibit increases in [Ca2+]i at concentrations between 1 microM and 1 mM. These agents also decrease [Ca2+]i changes produced by kainate and potassium, but to a smaller extent. As the effects of NO are still present following alkylation of the redox modulatory site on the NMDA receptor this action of NO is probably not a consequence of oxidation of the redox site. In contrast to SNP, ISDN does not inhibit NMDA-induced whole cell patch-clamp currents suggesting that NO modulates [Ca2+]i via perturbation of a Ca2+ homeostatic process. Furthermore, SNP may have a direct action on the NMDA receptor complex in addition to the generation of NO. 8-Bromo-cGMP does not mimic the inhibitory effect of NO suggesting that this effect is not the result of NO stimulation of neuronal cGMP production. As the production of NO in neurons is dependent on increases in [Ca2+]i associated with NMDA receptor activation, these data suggest that NO-mediated decreases in [Ca2+]i may represent a novel feedback inhibitory mechanism for NO production in the brain. PMID- 1450921 TI - Presence of D-alanine in proteins of normal and Alzheimer human brain. AB - This report constitutes the first demonstration of the presence of D-alanine in the proteins of the human nervous system. Proteins of the frontal lobe white and gray matter of human brains, both normal and Alzheimer subjects, contain D alanine at concentrations between 0.50 and 1.28 mumol/g of wet tissue, 50-70 times lower than the concentration of L-alanine. Both white and gray matter of Alzheimer brains contain D-alanine 1.4-times higher than the respective regions of normal brains. The gray matter proteins of Alzheimer brains show a highly significant 8% decrease in total alanine content, when compared with normal brain gray matter proteins. Since Alzheimer's disease is exhibited by deterioration of the gray matter, the occurrence of elevated D-alanine levels in the gray matter of Alzheimer brains is a significant discovery and raises the question whether this enantiomer causes the degeneration of the gray matter proteins in Alzheimer's disease, or whether it is an effect of the disease. PMID- 1450922 TI - Regeneration of neural lobe-like neurovascular contact regions in explanted neural lobes placed in the hypothalamo-neurohypophysial tract in the lateral retrochiasmatic area. AB - Neural lobes that had been explanted 30 days earlier were transplanted into retrochiasmatic lesions of the hypothalamo-neurohypophysial tract 15 days before being observed by electron microscopy and neurophysin immunohistochemistry. Neurovascular contact regions consisting of microvascular networks surrounded by neurophysin-immunoreactive terminals developed in 86% of the grafted explants. The fine structure of such regions resembled that of the neural lobe, with palisades of neurosecretory axon terminals abutting the basal laminae associated with the microvessels and plexuses of neurosecretory axons occupying the spaces within the vascular network. Both continuous and fenestrated blood vessels were present. Lamellopodia from glial cells partially ensheathed both axons and terminals, and sometimes separated the terminals from the perivascular basal lamina. Profiles in which neurosecretory granulated vesicles were depleted and many microvesicles were present were interpreted as terminals from which hormones had been released. No regeneration occurred into explants that had been cryotreated to kill their pituicytes and other cells before transplantation. These observations demonstrate that neurosecretory axons served in the hypothalamus can regenerate to form a new neural lobe-like structure when an appropriate microenvironment is available, and that neural lobes explanted 21 days earlier retain the elements required to supply that microenvironment. They also provide evidence that viable pituicytes are essential for regeneration of neurosecretory axons and terminals into transplanted explants. PMID- 1450923 TI - Iron and transferrin uptake by brain and cerebrospinal fluid in the rat. AB - Iron and transferrin uptake into the brain, CSF and choroid plexus, and albumin uptake into the CSF and choroid plexus, were determined after the intravenous injection of [59Fe-125I]transferrin and [131I]albumin into control rats aged 15, 21 and 63 days and 21-day iron-deficient rats. Iron uptake by the brain was unidirectional, greatly exceeded that of transferrin and was equivalent to 39 and 36% of the plasma iron pool per day in the 15-day control and 21-day iron deficient rats. The rate of transferrin catabolism in the rats was only about 20% of the plasma pool per day. Iron and transferrin uptake into the brain and CSF decreased with increasing age and was greater in the iron-deficient than in the control 21-day rats. The quantity of 125I-transferrin recovered in the CSF could account for only a small proportion of the iron taken up by the brain. Albumin transfer to the CSF also decreased with age but was lower than that of transferrin and was not affected by iron deficiency. Similarly, the plasma: CSF concentration ratios of transferrin and albumin, as determined immunologically, decreased with age and were greater for transferrin than albumin. It is concluded that iron uptake by the brain is dependent on iron release from transferrin at the cerebral capillary endothelial cells with recycling of transferrin to the plasma and transfer of the iron into the brain interstitium. Only a small fraction of the transferrin bound by brain capillaries is transcytosed into the brain and CSF, this being one source of CSF transferrin while other sources are local synthesis and transfer from the plasma by the choroid plexuses. PMID- 1450924 TI - Saturable uptake of [125I]L-triiodothyronine at the basolateral (blood) and apical (cerebrospinal fluid) sides of the isolated perfused sheep choroid plexus. AB - The uptake of 125I-labelled L-triiodothyronine (T3) was measured on the blood side of the isolated perfused choroid plexus of the sheep using steady-state and single-circulation paired tracer techniques. The steady-state uptake of T3 was 33.5% (perfusion fluid protein content was 0.05 g.dl-1) which could be reduced to 9.4% in the presence of 500 microM unlabelled T3 showing partial saturation. The CSF to blood steady-state [125I]T3 measurements gave plasma/CSF ratio, R%, of 24.6 +/- 4.8% which was reduced to 9.8 +/- 2.1% in the presence of 500 microM unlabelled T3 in the mock CSF. The transport of T3 across the blood face of the choroid plexus and the CSF to blood transport, failed to show sodium dependence. Using the single circulation paired tracer technique, the initial uptake in less than 60 s, Umax of [125I]T3 was 50.4 +/- 3.9% relative to the extracellular marker [3H]D-mannitol. However, when 250 microM unlabelled T3 was present, Umax was reduced by 66%, although further significant inhibition at higher concentrations was not observed. Uptake of T3 at the blood side of the choroid plexus was partially saturated in the presence of unlabelled reverse T3 and DT3, suggesting little uptake stereospecificity. Unlabelled thyroxine (T4) and the amino acid analogues cycloleucine (aminocyclopentane-1-carboxylic acid) and BCH (beta-2-aminobicyclo-[2,2.1]-heptane-2-carboxylic acid) each reduced [125I]T3 uptake significantly, but not to the same degree as T3 stereoisomers. The neutral amino acids alanine and phenylalanine, had no effect on uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450925 TI - Behavior of VRG neurons during the atonia of REM sleep induced by pontine carbachol in decerebrate cats. AB - The microinjection of carbachol into the pons of acute decerebrate cats elicits a REM sleep-like atonia and a profound suppression of respiratory motoneuronal activity (J. Appl. Physiol., 69 (1990) 2280-2289). To assess whether this suppression is mediated by medullary neurons that provide respiratory drive to motoneurons of the respiratory pump muscles (diaphragm and intercostals), we studied the effect of pontine carbachol on the activity of neurons of the ventral respiratory group (VRG) in decerebrate, vagotomized, paralyzed and artificially ventilated cats. VRG neurons were recorded extracellularly along with the activity of phrenic and intercostal (external and internal) nerves. Both inspiratory (I) and expiratory (E) VRG neurons had incrementing, ramp-like bursts of activity during their firing periods and were not vagal motoneurons. Carbachol produced a depression of the peak firing rate in most (42/57) neurons studied. However, five cells showed no change and ten had an increase in activity in spite of consistent depression at the motoneuronal level. For the total population of cells (34 I and 23 E), the peak firing was reduced to 88.5% +/- 16.3 (S.D.) of control. The simultaneously recorded phrenic activity was reduced to 77.9% +/- 11.5, while inspiratory intercostal activity fell to 63.4% +/- 21.6 and expiratory to 23.2% +/- 21.2 of control. The carbachol-induced changes in peak firing of both I and E cells were quantitatively similar, and positively correlated to changes in peak phrenic activity. Analysis of this correlation suggested that phrenic and intercostal activities will be depressed to some degree by carbachol even when the average VRG cell activity remains unchanged. In addition, our data show that VRG cells may receive a combination of inhibitory and excitatory inputs during the carbachol-induced depression of respiratory motoneurons. Thus, although some disfacilitation from VRG cells may occur, there must be additional inhibitory or disfacilitatory pathways that mediate the decrease in activity of both phrenic and intercostal motoneurons that accompanies the REM sleep-like atonia. PMID- 1450926 TI - Graded postischemic reoxygenation reduces lipid peroxidation and reperfusion injury in the rabbit spinal cord. AB - The effect of graded postischemic reoxygenation on lipid peroxidation, neurological recovery and the degree of spinal cord damage after 20 min abdominal aorta ligature was tested in the rabbit. In comparison with normoxic recirculation, the graded postischemic reoxygenation (GPIR) during early phase of reperfusion (30 min) significantly reduced the level of lipid peroxidation products (LPP) in vivo and in vitro after 1 h survival. Neuropathological changes in animals with normoxic reperfusion showed gradual deterioration ranging from appearance of heavy argyrophilic neurons after 1 h reperfusion followed by neuronal necroses after 12 h survival to the development of an extensive spongy lesion reaching ventral horn and intermediate zone 2 days postoperatively. The neuroprotective effect of graded postischemic reoxygenation was evident even after 2 days survival with preserved structural integrity of the gray matter as confirmed by light and electron microscopy. The results indicate that graded postischemic reoxygenation during 1 h reperfusion can reduce lipid peroxidation and suppress irreversible neuronal damage using developing during the early reperfusion phase. PMID- 1450927 TI - Effects of calcium on the dynamic process of transmitter release which generates either skew- or bell-MEPPS. AB - Miniature endplate potential (MEPP) amplitudes, MEPP frequencies and ratios of skew:bell-MEPPs were determined as well as synaptic vesicle diameters and densities at the mouse diaphragm neuromuscular endplate during exposure to elevated calcium concentrations. Additions of external Ca2+ had variable effects on MEPP frequencies and percentages of skew-MEPPs, regardless of concentrations used (1-25 mM). Nevertheless, changes in MEPP amplitudes were most sensitive (4 fold decrease) to low value increases of Ca2+. Changes in MEPP frequencies produced by an increase in Ca2+ were very sensitive to initial frequencies as well as the initial calcium concentration. An increase in Ca2+ usually increased MEPP frequency (providing skew-MEPPs were measured). Changes in the percentage of skew-MEPPs were extremely variable (4-90%) and these changes depended on initial frequencies, initial skew- to bell-MEPP ratios and age of the mouse. With a change in Ca2+ concentration, synaptic vesicle diameters and densities remained constant during changes in MEPP frequencies and large changes in the skew:bell MEPP ratios; and, vesicle numbers were sometimes slightly increased. Because of the wide range in MEPP frequencies and amplitudes, this study demonstrates that the effect of various treatments should be evaluated on identified endplates and that analyses of randomly selected endplates must consider the large variability between endplates. These results show that the skew-MEPP class must not be ignored in studies of spontaneous MEPP release, and that initial frequencies and age of the mouse are also important in evaluating changes in skew-MEPP to bell MEPP ratios. The rapid changes in skew- to bell-MEPP classes indicate that MEPP class and size are determined at the moment of release by the state of the release process as proposed by Kriebel et al. (1990). Because changes in calcium concentration can immediately alter the ratio of skew- to bell-MEPPs we conclude that the release process has two states to generate the two classes of MEPPs, and that the release process is very sensitive to conditions so that states are easily changed. We propose that the release process meters transmitter in subunit amounts to form both classes of MEPPS and that the calcium ions modulate the process. PMID- 1450928 TI - Hippocampal activity, olfaction, and sniffing: an olfactory input to the dentate gyrus. AB - Experiments in freely moving rats showed that olfactory stimuli elicit a burst of rhythmical 15-30 Hz waves in or near the hilus of the dentate gyrus but not in adjacent regions of CA1. This fast wave burst is not elicited by visual, auditory, or somatosensory inputs and is not related to motor activity. Electrical stimulation of the olfactory bulb evokes a complex potential in the hilus of the dentate gyrus but not in adjacent regions of CA1. Experiments making use of wave-triggered averaging demonstrated that there is a degree of phase locking between (a) hippocampal RSA and sniffing or other respiratory patterns, (b) hippocampal RSA and the initiation of jumping, and (c) respiration and the initiation of jumping. An early hypothesis that the hippocampus and dentate gyrus are part of an olfacto-motor mechanism may merit re-examination. PMID- 1450929 TI - N-methyl-D-aspartate and vasopressin activate distinct voltage-dependent inward currents in facial motoneurones. AB - Facial motoneurones of the rat respond to arginine vasopressin by generating a voltage-dependent inward current which is sodium-dependent and is resistant to tetrodotoxin. In the present study, we have investigated the action of N-methyl-D aspartate (NMDA) on these same neurones. We have obtained single-electrode voltage-clamp recordings from brainstem slices of newborn rats. In a majority of vasopressin-sensitive facial motoneurones, NMDA induced an inward current. This action was direct, was concentration-related and could be suppressed by the specific competitive antagonist D-2-amino-5-phosphopentanoic acid (D-AP5). The NMDA-evoked current increased in amplitude as the neuronal membrane was depolarized. It could be blocked by the noncompetitive antagonist MK-801. It was potentiated following removal of extracellular magnesium, and was attenuated or suppressed when the external magnesium concentration was increased from 1 to 10 mM. By contrast, none of these treatments affected the vasopressin-induced current. These results show that facial motoneurones in the rat possess functional NMDA receptors and indicate that NMDA and vasopressin affect the bioelectrical properties of these neurones by turning on distinct voltage dependent inward currents. PMID- 1450930 TI - Isradipine is able to separate morphine-induced analgesia and place conditioning. AB - The effect of isradipine, a dihydropyridine calcium antagonist, on morphine induced place preference and analgesia in rats and mice was studied. Isradipine (0.6-5.0 mg/kg s.c.) inhibited an acquisition of morphine-induced place preference in rats and mice in a dose-related manner. Isradipine did not affect or strengthen morphine-induced analgesia as measured by tail-clip and hot-plate tests in mice and tail-clip and tail-flick tests in rats. The results suggest that analgesic and reinforcing effects of morphine might be pharmacologically separated by isradipine. PMID- 1450931 TI - Calbindin D-28k and choline acetyltransferase are expressed by different neuronal populations in pedunculopontine nucleus but not in nucleus basalis in squirrel monkeys. AB - Single- and double-immunostaining procedures were used to study the distribution of the acetylcholine synthesizing enzyme choline acetyltransferase (ChAT) and the calcium binding protein calbindin D-28k in the nucleus basalis of Meynert (nbM) and in the pedunculopontine nucleus (PPN) of the squirrel monkey (Saimiri sciureus). As expected from previous studies in other primates, including humans, the nbM in the squirrel monkey is enriched with large ChAT-immunoreactive neurons that form clusters in the substantia innominata. Some ChAT-positive neurons are also scattered more dorsally within the internal and external medullary laminae of the pallidal complex. A smaller number of calbindin-immunoreactive cells occur in the same locations and their mean cross-sectional somatic area (424 microns 2) is not significantly different from that of the ChAT-immunoreactive cells (450 microns 2). Furthermore, 60% of the ChAT-immunopositive cells in the nbM display calbindin immunoreactivity. Most of these double-immunoreactive neurons occur in the typical clusters of the nbM, whereas the large neurons scattered in between the clusters display ChAT immunoreactivity only. In the PPN, ChAT-positive neurons are scattered around and partly within the superior cerebellar peduncle and also form a dense cluster in the lateral portion of the mesopontine tegmentum. Calbindin-immunoreactive cells also abound around the superior cerebellar peduncle, but they are more sparsely distributed and cover a larger sector of the tegmentum than the ChAT-positive neurons. These calbindin immunoreactive cells are significantly smaller (200 microns 2) than the ChAT immunoreactive cells (471 microns 2) and no double-immunostained neurons are present in the PPN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1450932 TI - Sex differences of hypothalamic prolactin cells develop independently of the presence of sex steroids. AB - There is evidence for a hypothalamic prolactin (PRL) system that expresses sexually dimorphic traits. The aim of this in vitro study is to gain an insight into the process of sexual differentiation of hypothalamic PRL cells. In particular, we wanted to determine whether sexual differentiation of these cells can occur independently of the surge of gonadal testosterone which, in the male rat embryo, takes place at embryonic day (E) 18 and is commonly believed to start the critical period of sexual differentiation of the brain. Gender-specific cell cultures were prepared from E 14 or E 17 rat diencephalon and raised in the absence of gonadal steroids. After 10 days in vitro, numbers of PRL immunoreactive (IR) cells and PRL levels were quantified by immunocytochemistry and Western blotting, respectively. Numbers of PRL-IR cells and PRL levels were 2 3 times higher in cultures prepared from female than from male embryos of either age. It is concluded that sexual differentiation of hypothalamic PRL cells starts well before the generally acknowledged onset of the critical period and may proceed independently of the action of gonadal testosterone. Besides gonadal steroids, other mechanisms, such as cell-intrinsic realization of a sex-specific genetic program, may be responsible for initiating the development of sexually dimorphic neuronal phenotypes. PMID- 1450933 TI - Activation of the dentate gyrus by pentylenetetrazol evoked seizures induces mossy fiber synaptic reorganization. AB - Kindled seizures evoked by electrical stimulation of limbic pathways in the rat induce sprouting and synaptic reorganization of the mossy fiber pathway in the dentate gyrus (DG). To investigate whether seizures evoked by different methods also induce reorganization of this pathway, the distribution of mossy fiber terminals in the DG was examined with Timm histochemistry after systemic administration of pentylenetetrazol, a chemoconvulsant that reduces Cl- mediated GABAergic inhibition. Myoclonic seizures evoked by subconvulsant doses of pentylenetetrazol (24 mg/kg i.p.) were not accompanied by electrographic seizures in the DG, and did not induce mossy fiber sprouting. Generalized tonic-clonic seizures evoked by repeated administration of PTZ (24 mg/kg i.p.) were consistently accompanied by electrographic seizure activity in the DG, and induced sprouting and synaptic reorganization of the mossy fiber pathway. The results demonstrated that repeated generalized tonic-clonic seizures evoked by pentylenetetrazol induced mossy fiber synaptic reorganization when ictal electrographic discharges activated the circuitry of the DG. PMID- 1450934 TI - Effects of 1,3-di-o-tolylguanidine (DTG), a sigma ligand, on local cerebral glucose utilization in rat brain. AB - The 2-deoxy-D-[1-14C]glucose ([14C]DG) method was used to examine the effects of the relatively selective sigma ligand 1,3-di-o-tolylguanidine (DTG) on cerebral metabolism in freely moving rats. Each animal received an i.p. injection of DTG (0.2, 1, or 5 mg/kg) or normal saline 20 min prior to the infusion of [14C]DG. DTG induced dose-dependent changes in local cerebral glucose utilization (LCGU) in several motor and limbic structures. Most structures showed increases in LCGU, with a maximum effect at 1 mg/kg. The most profound increases in LCGU were observed in brain regions that are rich in sigma receptors. These included cerebellar and related nuclei (interpositus, lateral and medial cerebellar n., vestibular n., olivary n.), ambiguus n., superior colliculus (superior layers), hippocampus (CA2, CA3, DG), n. basalis of Meynert interpeduncular n., and the substantia nigra pars compacta and pars reticulata. No significant decreases in glucose utilization were observed at any dose. Although the areas affected by DTG are similar to those previously reported for other sigma ligands, future studies employing a range of doses for additional selective sigma ligands must be carried out in order to confirm whether these changes in LCGU were sigma-mediated. PMID- 1450935 TI - High molecular weight basic fibroblast growth factor-like protein is localized to a subpopulation of mesencephalic dopaminergic neurons in the rat brain. AB - A rabbit antiserum (R917) was raised to a purified fraction of bovine brain basic fibroblast growth factor (bFGF). On Western blots of rat midbrain extract, the antiserum did not recognize low molecular weight forms of bFGF. Instead, it recognized a single band of 27-28 kDa. Immunohistochemically, the antiserum preferentially stained a subpopulation of calbindin-negative mesencephalic dopaminergic neurons. The positive somata were mainly packed in a ventral portion of the tegmentum including the A10 region, the ventral tegmental area and the pars compacta of the medial substantia nigra, but were also scattered in both the pars compacta and reticulata portions of the lateral substantia nigra. Processes of dendrites and axons were clearly visible. Terminal fields were located in striosomes, the dorsolateral rim of the neostriatum, the anterodorsal aspect of the nucleus accumbens shell, the infralimbic cortex, and the medial prefrontal cortex. These results suggest that trophic specialization in subpopulations may occur in all three of these dopaminergic projection systems, i.e. the nigrostriatal, mesolimbic and mesocortical pathways. PMID- 1450936 TI - Anticonvulsant effect of intranigral fluoxetine. AB - Bilateral focal injections of the serotonin uptake inhibitor, fluoxetine (1.75 7.0 nmol) into substantia nigra (SN) protected against convulsive seizures evoked by the focal injection of bicuculline methiodide into area tempestas, an epileptogenic site within the deep prepiriform cortex. Injection of fluoxetine unilaterally in SN or bilaterally into a site dorsal to SN was not anticonvulsant. Blockade of nigral gamma-aminobutyric acid (GABA) receptors with bicuculline in SN did not reverse the anticonvulsant action of intranigral fluoxetine. These data suggest that serotonergic transmission in SN exerts a seizure suppressing action which is independent of GABA transmission in SN. PMID- 1450937 TI - Amphibian olfactory receptor neurons express olfactory marker protein. AB - Expression of olfactory marker protein (OMP) in olfactory receptor neurons (ORNs) in two amphibians was investigated by immunohistochemical methods. The OMP immunoreactivity was observed in the cilia, apical dendritic knobs, dendrites and somas of ORNs; the axons of ORNs also showed intense immunoreactivity for OMP throughout their course from the olfactory epithelium to the glomerular layer of the olfactory bulb. Seven days after olfactory nerve transection in salamander, the number of OMP-positive ORNs was markedly reduced in the ipsilateral epithelium. The results demonstrate that amphibian ORNs express OMP and confirm its phylogenetic conservation across diverse species. PMID- 1450938 TI - Chronic fluoxetine treatment reduces hypothalamic vasopressin secretion in vitro. AB - Patients with obsessive-compulsive disorder (OCD) hypersecrete the arousal producing neurohormone arginine vasopressin (AVP) into the cerebrospinal fluid and plasma. Because OCD responds preferentially to potent serotonin uptake inhibitors, we compared the effect of chronic fluoxetine treatment to that of other antidepressants (trazodone and desipramine) on AVP release from rat hypothalamic organ culture and showed that only fluoxetine significantly reduced in vitro AVP release. PMID- 1450939 TI - Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration. AB - The effects of withdrawal from cocaine on extracellular dopamine (DA) levels in the nucleus accumbens (NAC) were examined by intracranial microdialysis in awake rats after periods (9.5-21.75 h) of unlimited-access, intravenous cocaine self administration. Cocaine withdrawal was associated with significant reductions in basal DA overflow that persisted up to 12 h. Maximal inhibition of DA release (mean +/- S.E.M. 66.15 +/- 3.30 percent of basal levels) was observed between 4-6 h after cessation of cocaine intake and was positively correlated (r = 0.88) with the duration of the preceding self-administration episode. The results suggest that suppression of basal DA release in the NAC is an adaptive consequence of sustained cocaine exposure and may in part underlie the post-cocaine anhedonia observed in behavioral models of cocaine withdrawal. PMID- 1450940 TI - Amyloid precursor protein is localized in growing neurites of neonatal rat brain. AB - Previous studies have indicated that amyloid precursor protein (APP) might be a trophic agent in the nervous system, possibly through the regulation of cell adhesion and the protease/protease inhibitor activity. Additionally, APP is upregulated during the development of the nervous system. In order to further study the role of APP in neuritic outgrowth, we examined the patterns of distribution of APP in the immature neonatal rat brain (P1). Laser-scanning confocal imaging of double-immunolabeled sections showed that a subpopulation of the anti-GAP43-immunoreactive outgrowing neurites contained APP immunoreactivity in the neocortex and hippocampus. These fine, long neuritic processes were also positive with antibodies against phosphorylated neurofilaments and were glial fibrillary acidic protein (GFAP) negative. In addition, anti-APP strongly immunolabeled neurons in the inner cortical layers, while GAP43 strongly immunolabeled the neuropil surrounding them. These observations are consistent with a previous study where APP was localized to aberrant sprouting neurites and suggest a possible role for APP in neuritic outgrowth in plaques of patients with Alzheimer's disease (AD), which might explain the abnormal neuritic response found in AD. PMID- 1450941 TI - Comparison of anticonvulsant effects of valproic acid entrapped in positively and negatively charged liposomes in amygdaloid-kindled rats. AB - Intraperitoneal injection of free valproic acid (VPA) suppressed amygdaloid kindled seizure 1 h after injection in rats, but had no effect at 24 h. VPA entrapped in positively charged liposomes showed a prolonged anticonvulsant effect lasting for 2 days, while the effect evaluated at 1 h was not different from that with free VPA. VPA entrapped in negatively charged liposomes exerted a significantly stronger effect at 1 h than did free VPA, while it had no significant effect at 24 h. These results suggest that surface charges on liposomes play an important role in modifying the anticonvulsant effect of VPA. PMID- 1450942 TI - Effects of epidermal growth factor and basic fibroblast growth factor on generation of long-term potentiation in the dentate gyrus of fimbria-fornix lesioned rats. AB - The effects of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on long-term potentiation (LTP) in the dentate gyrus in vivo were investigated in fimbria-fornix (FF)-lesioned rats. Transection of FF resulted in decreased frequency of LTP generation. Intracerebroventricular injection of EGF (50 ng) and bFGF (50 ng) significantly facilitated LTP generation in the FF lesioned rats. These results suggest that EGF and bFGF can promote the hippocampal LTP impaired by loss of subcortical afferents. PMID- 1450943 TI - Differences in the dopaminergic innervation of the electroreceptive and mechanoreceptive medullary lateral line nuclei of the ray, Raja radiata. AB - An immunohistochemical study was made of the octavolateral centres in the medulla of a cartilaginous fish, using an antibody specific for dopamine. No immunopositive cell bodies were observed but dopaminergic fibres were present in parts of the region. The overlying cerebellar crest was devoid of dopamine; the dorsal (electroreceptive) nucleus was poorly innervated, but the medial (mechanoreceptive) nucleus received a rich dopaminergic innervation comprising very fine, varicose fibres. PMID- 1450944 TI - Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study. AB - The Laser Microprobe Mass Analyzer (LAMMA) is a sensitive instrument for identifying and localizing trace elements in tissue samples. Using LAMMA, we have examined melanin-containing neurons of the substantia nigra in patients with Parkinson's disease (PD) and controls. We found that iron significantly accumulates within neuromelanin granules of patients with PD compared to controls. Increased aluminum was found in the neuromelanin granules of 2 of 3 PD cases but in no controls. The accumulation of iron and aluminum, which are known to promote oxidant stress, may account for the selective degeneration of neuromelanin-containing neurons in PD. PMID- 1450945 TI - HIV-1 envelope protein evokes intracellular calcium oscillations in rat hippocampal neurons. AB - Treatment of single rat hippocampal neurons with 200 pM recombinant HIV-1 envelope glycoprotein, gp120, resulted in large increases in the intracellular free calcium concentration ([Ca2+]i) as measured with indo-1-based microfluorimetry. Three patterns of [Ca2+]i increases were observed: in one pattern the [Ca2+]i rose rapidly and transiently as a single peak, in a second pattern gp120 induced [Ca2+]i oscillations that subsided when the protein was removed, and in a third pattern the oscillations continued long after washout of gp120. Both single peak and oscillatory [Ca2+]i increases were completely blocked by the Ca2+ channel blocker nitrendipine (1 microM). The sustained oscillatory responses were also blocked completely and reversibly by the N-methyl-D-aspartate (NMDA) receptor antagonist CGS19755 (10 microM) and the Na+ channel blocker tetrodotoxin (1 microM). Complete block by antagonists of Ca2+, Na+, and NMDA gated ion channels suggests that at least two cells are required to maintain the [Ca2+]i oscillations. We hypothesize that gp120 acts as an excitotoxin by increasing synaptic activity in the network of neurons established in primary culture. PMID- 1450946 TI - The pontine parabrachial region mediates some of the descending inhibitory effects of stimulating the anterior pretectal nucleus. AB - Electrical stimulation of the anterior pretectal nucleus (APtN) elicits antinociception by inhibiting the responses of spinal multireceptive neurones to noxious stimuli. This descending inhibition is mediated, in part, by activating cells in the ventrolateral medulla. Neuronal tract tracing has previously shown that the APtN also projects directly to the pontine parabrachial region (PPR). The PPR, investigated by Katayama et al. (Brain Res., 296 (1984) 263-283), corresponds to the cholinergic cell group Ch5 of Mesulam et al. (Neuroscience, 10 (1983) 1185-1201). In this study, the pathway from APtN to PPR was investigated using urethane anaesthetised rats. Electrical stimulation (single square wave 0.2 ms pulses, 1-10 V, 5 Hz) of the APtN potently excites 40% of the cells recorded in the PPR. In the reverse experiment, stimulation of the PPR at the same parameters excited 36% of the cells recorded in the APtN. The contribution of this pathway to the spinal inhibitory effects of APtN stimulation was then examined. Unanaesthetised animals received electrical stimulation to the APtN (35 microA r.m.s., 15 s) and the increase in tail-flick latencies was measured. Bilateral electrolytic lesions of the PPR caused a 67% reduction of the antinociceptive effect of APtN stimulation. In urethane anaesthetised rats, microinjection of tetracaine into the PPR blocked the inhibition of multireceptive dorsal horn neurones caused by APtN stimulation (20 s train of 50 microA square wave 0.1 ms pulses, 100 Hz). In conclusion, these experiments strongly sugget that the PPR may be an important part of a descending antinociceptive pathway originating in the APtN. PMID- 1450947 TI - Primary culture of postnatal rat hypothalamic neurons in astrocyte-conditioned medium. AB - Mature functional hypothalamic neurons of male and female rats (21-day postnatal) were successfully cultured without attachment to non-neuronal cells in serum-free astrocyte-conditioned medium (ACM). A novel cell-collecting method was designed for these vulnerable cells by allowing the dissociated cell suspension to stand in a vertically held, wide-tipped syringe so that the cells were concentrated near the lower liquid surface, from which position they could be easily dropped into the medium, leaving most of the small debris in the syringe. This method made it possible to study statistically the survival of cultured neurons. It was impossible to collect many viable cells by the commonly used dissociating technique for fetal rat brain. However, neuron-like cells with a few processes could be isolated from sliced hypothalamic tissues by means of enzymatic and mechanical treatments. The original processes disappeared within 1-2 days and some new processes were generated after 2-3 days in vitro; the cells survived for 28 days in vitro. The cells were identified as neurons by the immunostaining method for microtubule-associated protein 2 (MAP2) and neurofilament (NF). Such neurons were obtained from every site of hypothalamic tissue sampled. These phenomena were not observed in chemically-defined medium (CDM), CDM supplemented with basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) or nerve growth factor (NGF). PMID- 1450948 TI - Systemic morphine reduces GABA release in the lateral but not the medial portion of the midbrain periaqueductal gray of the rat. AB - Neuroanatomical, electrophysiological and pharmacological studies have provided indirect evidence indicating that GABAergic neurons play a key role in opiate analgesia mediated by the midbrain periaqueductal gray (PAG) and ventromedial medulla. Although these studies suggest that systemic administration of opiates inhibits GABA release in the PAG, there have been no investigations to date that have directly examined this issue. The present study was thus designed to determine whether systemic morphine injection inhibits GABA release in the PAG of awake, freely moving rats using in vivo microdialysis and subsequent HPLC analysis. Extracellular levels of GABA, glutamate, aspartate, glycine, homocysteic acid and taurine were monitored with the microdialysis technique in either the lateral or medial portion of the ventrocaudal PAG in unanesthetized, unrestrained rats. Amino acid release was induced by infusing veratridine (75 microM, a sodium channel activator) directly through the dialysis probe. The effect of veratridine alone and the effect of veratridine in the presence of systemic morphine on the concentrations of amino acids in the PAG dialysate were determined. There were no significant differences in the basal concentrations of GABA, taurine, aspartate, glutamate, homocysteic acid and glycine between dialysates collected from the medial versus the lateral ventrocaudal PAG. Glycine, taurine and glutamate were present in the highest concentrations in dialysis samples both before and after treatment with veratridine, whereas GABA, homocysteic acid and aspartate were present in the lowest concentrations. Perfusion of veratridine into the ventrocaudal PAG resulted in significant elevation of all amino acids investigated. Except for taurine, no significant difference in veratridine-induced release between the lateral and medial PAG was observed. Tetrodotoxin (TTX) significantly blocked veratridine-induced release of GABA, aspartate, glutamate, glycine and taurine but not homocysteic acid. When rats were injected with morphine (10 mg/kg i.p.), veratridine-induced release of GABA was selectively and significantly decreased in the lateral but not the medial PAG as compared to control rats injected with saline followed by veratridine perfusion. Systemic injection of morphine or saline caused no significant change in the basal concentration of amino acids in PAG dialysate samples. These findings are consistent with the proposed mechanism of action of morphine in the lateral ventrocaudal PAG and offer the first direct evidence that systemic opiates decrease GABA release in this midbrain region. PMID- 1450949 TI - Effects of prazosin on the blood-brain barrier during experimental autoimmune encephalomyelitis. AB - Alterations in normal function of the blood-brain barrier (BBB) are important in the pathophysiology of multiple sclerosis and its laboratory counterpart, experimental autoimmune encephalomyelitis (EAE). As part of studies on drugs that affect vascular tone in rats with EAE, we have shown previously that the specific alpha 1-adrenoreceptor antagonist, prazosin, suppressed clinical and pathologic disease. In the present study we used quantitative morphometric analysis of capillary endothelium and the tracer horseradish peroxidase (HRP) to define effects of this drug on vascular events associated with central nervous system edema. In prazosin-treated and saline-treated EAE rats, protein extravasation in the spinal cord correlated with clinical presentation. Consistent with our previous data, the results showed that increased edema was associated with increased vesicular content of capillary endothelium. In prazosin-treated rats with no clinical signs, vesicular content was comparable to that found in normal animals. With increasing severity of disease, vesicular content increased and mitochondrial content decreased. In both prazosin- and saline-treated rats, mitochondrial content was reduced even when clinical signs were slight, and sharply declined when clinical signs increased. These results suggest that damage to mitochondria may be associated with early pathological events. In prazosin treated animals, HRP accumulated in pericytes, suggesting that these cells were a target for the action of prazosin and may restrict the extravasation of fluid into the perivascular parenchyma. Our results underscore the presence of capillary changes associated with inflammation of the central nervous system, in addition to the well-recognized cellular inflammation that is targeted to the venular bed. The extent of capillary changes was closely associated with extent of tracer leakage in the spinal cord and support the conclusion that transcytotic vesicles are involved in transport of edema fluid during EAE, and that high mitochondrial levels are important for the normal function of BBB endothelium. PMID- 1450950 TI - A1 neurons and excitatory amino acid receptors in rat caudal medulla mediate vagal excitation of supraoptic vasopressin cells. AB - Extracellular recordings from the supraoptic nucleus of the rat established that vasopressinergic neurosecretory cells were excited by stimulation of cervical but not abdominal vagal afferents. This response was absent or significantly attenuated after microinjection of gamma-aminobutyric acid into a region of the caudal medulla known to contain the A1 noradrenaline cell group. Consistent with the possible involvement of the A1 group, vagal stimulation approximately doubled the frequency of proto-oncogene expression in A1 noradrenaline neurons, as indicated by the occurrence of nuclear Fos-like immunoreactivity in tyrosine hydroxylase-positive neurons of the caudal ventrolateral medulla. Finally, A1 region microinjection of either the N-methyl-D-aspartic acid (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV), or the non-NMDA antagonist 6 cyano-7-nitroquinoxaline-2,3-dione (CNQX), significantly reduced vasopressin cell responses to vagal stimulation. These findings suggest that: (i) the A1 group is an essential component in a pathway which relays facilitatory vagal input of cardiopulmonary origin to neurosecretory vasopressin cells, and (ii) the activation of A1 neurons in this pathway involves both NMDA and non-NMDA excitatory amino acid receptors, an observation consistent with an input to A1 cells which generates 'mixed' excitatory postsynaptic potentials. PMID- 1450951 TI - Convergence and segregation of septal and median raphe inputs onto different subsets of hippocampal inhibitory interneurons. AB - The convergence and segregation of medial septal and median raphe afferents in the innervation of different subpopulations of GABAergic interneurons was investigated in the rat hippocampal formation. Following local injections of 5,7 dihydroxytryptamine into the median raphe nucleus destroying all serotonergic neurons, iontophoretic injections of Phaseolus vulgaris leucoagglutinin (PHAL) into the medial septum resulted in anterograde labelling of axons in the hippocampus. The labelled varicose fibres made multiple contacts with calbindin D28K-, parvalbumin-, and cholecystokinin-immunoreactive interneurons. These results disproved the possibility that PHAL-labelled afferents innervating hippocampal interneurons following septal PHAL injections would have been raphe axons passing through the injection site. In the second set of experiments a double anterograde tracing technique (PHAL from the septum and biotinylated-PHAL from the median raphe) and a triple or double immunostaining procedure was used to determine the types of interneurons (calbindin D28K-, parvalbumin-, or cholecystokinin-immunoreactive) innervated by one, or the other, or both pathways. The results showed that parvalbumin-containing neurons were innervated by septal afferents but avoided by raphe axons, whereas calbindin D28K-containing cells, and to a smaller extent cholecystokinin-containing cells served as targets for both pathways. In some cases the same individual calbindin D28K- or cholecystokinin-containing neurons received multiple contacts from afferents of both septal and raphe origin. Thus, our results indicate that different subcortical nuclei modulate largely different inhibitory circuits in the hippocampal formation. However, considering the occasional convergence of the two subcortical nuclei not only onto the same type, but even onto the same individual calbindin D28K-containing interneurons, we propose that a particular inhibitory function, most probably feed-forward inhibition in the distal dendritic region, is under the control of both pathways. PMID- 1450952 TI - Progressive transformation of the cytoskeleton associated with normal aging and Alzheimer's disease. AB - Transitional and end-stage forms of neurofibrillary tangles associated with normal aging and Alzheimer's disease were identified using thioflavine staining combined with tau and neurofilament protein immunofluorescence. Normal aging was marked by transitional pathology in layer II of the entorhinal cortex but no neurofibrillary tangles in prefrontal cortex, whereas, in Alzheimer's disease cases, layer II entorhinal neurons had progressed to end-stage neurofibrillary tangles and the prefrontal cortex contained a high representation of transitional forms of the neurofibrillary tangle. PMID- 1450953 TI - Magnetic resonance imaging of neural transplants in rat brain using a superparamagnetic contrast agent. AB - Rat fetal brain tissue was incubated in vitro with superparamagnetic ferrite particles covalently coupled to the lectin wheat germ agglutinin (WGA) and transplanted into the adult rat striatum. At 6 days and at 3 weeks post-surgery the transplants were observed on T1 weighted magnetic resonance (MR) images of the rat head as an area of relatively low signal intensity which could be clearly differentiated from the higher signal intensity produced by the host brain. Histological analysis revealed that the ferrite particles were largely restricted to the transplant in a patchy distribution. The ferrite particles were associated with cells having an apparent normal morphology. Superparamagnetic ferrite particles act as potent MR contrast agents and can be used to label transplanted cells. The labeled cells are apparently not adversely affected by the WGA-ferrite particles and can be monitored for at least three weeks in vivo using noninvasive MR imaging. PMID- 1450954 TI - Neuroprotective effect of protein kinase C inhibitors on oxygen/glucose free induced decreases in 2-deoxyglucose uptake and CA1 field potentials in rat hippocampal slices. AB - Staurosporine, a protein kinase C inhibitor, was found to produce a neuroprotective effect against an ischemic insult in both gerbils and rats in vivo. We have demonstrated that rat hippocampal slices exposed to oxygen/glucose free medium showed decreases in 2-deoxyglucose (2-DG) uptake and CA1 field potentials elicited by the stimulation of Schaffer collaterals. Therefore we examined the effect of protein kinase C inhibitors on oxygen/glucose free-induced impairments of 2-DG uptake and CA1 field potentials. Pretreatment with staurosporine, K252a and H-7 attenuated decreases in 2-DG uptake and CA1 field potentials. Treatment with phorbol ester, a protein kinase C activator, for a long period (90 min) was found to induce a down-regulation of protein kinase C activity. Therefore we examined the effect of pretreatment with phorbol ester for 90 min on oxygen/glucose free-induced decreases in 2-DG uptake and CA1 field potentials. These decrements were not attenuated by 5-min treatment with phorbol ester but were attenuated by 90-min treatment. The present results suggest that the treatment which decreases protein kinase C activity shows a neuroprotective action against oxygen/glucose free-induced deficits of metabolic and synaptic activity in hippocampal slices. PMID- 1450955 TI - Intravenous angiotensin II induces Fos-immunoreactivity in circumventricular organs of the lamina terminalis. AB - Conscious rats were infused intravenously with either angiotensin II (30-55 pmol/kg/min), isotonic saline or phenylephrine for 2 h, then killed. Fos was identified by immunohistochemistry in the brains. Fos expression occurred in many neurons of the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) with angiotensin infusion but not with isotonic NaCl or phenylephrine. Fos immunoreactivity was induced in cells in several medullary, hypothalamic and limbic structures with infusions of angiotensin II or phenylephrine at pressor doses. The results suggest that blood-borne angiotensin II at physiological levels causes angiotensin receptive neurons in the subfornical organ and OVLT to express Fos. Activation of baroreceptor pathways may also induce Fos expression at several other sites. PMID- 1450956 TI - Redirection of the hypoglossal nerve to facial muscles alters central connectivity in human brainstem. AB - Functional motor control requires perfect matching of central connectivity of motoneurones with their peripheral connections. However, it is not known to what extent central circuitry is influenced by target muscles, either during development or following a lesion. Surgical interventions aimed at restoring function following peripheral nerve lesions provide an opportunity for studying this interaction in the mature human nervous system. We have followed 8 patients in whom the hypoglossal nerve was anastomosed into a lesioned facial nerve, allowing voluntary contractions of the previously paralyzed muscles. We show that, in addition to replacing the facial neurons at peripheral synapses, a new short-latency trigemino-hypoglossal reflex, of the R1 blink reflex type, can be demonstrated in patients showing recovery, implying a sprouting of trigeminal neurons towards hypoglossal motoneurones, over a distance of at least 0.5 cm. These surprising results show an unexpected influence of the periphery in remodelling central connectivity in man. PMID- 1450957 TI - Mild traumatic brain injury enhances muscarinic receptor-linked inositol phosphate production in rat hippocampus. AB - Recent evidence suggests that muscarinic receptors play a role in the hippocampal hypersensitivity to imposed ischemia following mild traumatic brain injury (TBI). In rat hippocampal tissue, carbachol-stimulated inositol phosphate production was found to be enhanced by mild TBI, at 1 h post injury. This finding suggests that mild TBI may result in enhanced coupling between muscarinic receptors and phosphoinositide hydrolysis, which may contribute to post-traumatic hippocampal vulnerability to secondary ischemia. PMID- 1450958 TI - Sexual dimorphisms in the soma size of neurons in the brain of whiptail lizards (Cnemidophorus species). AB - Soma area was significantly larger in the anterior hypothalamus-preoptic area of male than female Cnemidophorus inornatus, and it was significantly larger in females than males in the ventromedial hypothalamus. These results parallel those on the volume of the brain areas in these animals, and therefore probably explain at least part of the dimorphisms seen in this sexually reproducing species. Soma size in parthenogenetic C. uniparens also parallels volume. PMID- 1450959 TI - The progressive changes of neuronal activities of the nigral dopaminergic neurons upon withdrawal from continuous infusion of cocaine. AB - Sensitivity of the nigral dopamine neurons to intravenous apomorphine was examined in rats pretreated with continuous cocaine or saline for two weeks. One day after withdrawal from pretreatment, a subsensitivity was observed while a supersensitivity was found on day 7, along with a significant increase in the baseline firing rates. In humans, an increased sensitivity of dopamine soma/dendritic autoreceptors may partly account for the symptomatology associated with the intermediate phase of withdrawal from cocaine binges. PMID- 1450960 TI - Short latency excitation of upper cervical respiratory neurons by vagal stimulation in the rat. AB - Extracellular recordings were made from 29 respiration-phased neurons in the upper cervical spinal cord (C1-C3) in nine anesthetized rats while ipsilateral and contralateral vagi were stimulated via platinum hook electrodes. Neuronal responses to vagal stimulation were recorded using peristimulus histograms. An accumulation of spikes with an average latency of 4.0 +/- 0.8 (S.D.) ms occurred in 11 cells after ipsilateral stimulation. These results indicate that there are fibers in the vagus which oligosynaptically excite respiratory neurons in the upper cervical spinal cord. PMID- 1450961 TI - Activation of paraventricular neurosecretory cells by local osmotic stimulation of the median preoptic nucleus. AB - Both electrical and local osmotic stimulation of the median preoptic nucleus (MnPO) predominantly produced excitation of paraventricular (PVN) neurosecretory cells in the rat. By contrast osmotic stimulation of the medial septal region was without effect, although electrical stimulation excited most cells. The results suggest that the MnPO is one of the osmosensitive sites controlling electrical activity of PVN neurosecretory cells. PMID- 1450962 TI - Gamma-glutamyltaurine has potent and long-lasting antiepileptic action as demonstrated by intra-amygdaloid injection in amygdala-kindled rats. AB - Intra-amygdaloid injections of gamma-glutamyltaurine, a recently identified brain dipeptide, strongly suppressed seizures in amygdala-kindled rats stimulated with intensities 10 or 50 microA above the generalized seizure triggering threshold (mean 82 microA). The suppressive effect persisted as long as 3 days. Taurine had relatively weak suppressive effects. Thus gamma-glutamyltaurine seems much more potent than taurine in the suppression of epileptic seizures when injected directly into the kindling site. PMID- 1450964 TI - The ecorche model and Pre-Vesalian medical illustration. PMID- 1450963 TI - A continuing signal maintains NGF receptor expression in hypoglossal motor neurons after crush injury. AB - Inhibition of axonal transport by vincristine applied to hypoglossal nerves 7 days after crush injury turns off the usual injured-induced expression of low affinity nerve growth factor receptor (p75NGFr). Vincristine applied proximal but not distal to the crush prevents p75NGFr induction. These results indicate that a continuing signal is axonally transported from the crush site that induces and maintains p75NGFr expression by injured motor neurons. PMID- 1450965 TI - Leonardo da Vinci's anatomy revisited. PMID- 1450966 TI - Depth studies: illustrated anatomies from Vesalius to Vicq d'Azyr. PMID- 1450967 TI - Visions of body and soul. AB - Inspiration for the Sacred Mirrors emerged after I had a series of mystical experiences that caused me to redefine my view of consciousness and the self. I saw the body as not just a solid isolated object in a world of separate forms and existential anxiety, but more like a manifestation of primordial energy of awareness that was everywhere present.... I wanted my paintings to visually chart the spectrum of consciousness from material perception to spiritual insight, and to function, if possible, as symbolic portals to the mystical dimension.... The obvious way was to present a believable and almost hyper-real portrayal of the physical body and then seduce the viewer into the stranger mystical dimensions. PMID- 1450968 TI - Value of magnetic resonance imaging as perceived by referring clinicians. PMID- 1450969 TI - Magnetic resonance imaging of reconstructed knee ligaments. AB - Reconstruction of knee ligaments is now a common orthopedic procedure. Patients are frequently referred for magnetic resonance imaging (MRI) after later reinjury, and the ability to recognize normal reconstructed knee ligaments is therefore becoming increasingly important. This pictorial essay demonstrates various reconstructions of the cruciate and the collateral ligaments, as well as several abnormalities of these ligaments. PMID- 1450970 TI - Fetal cystic hygromas: further insights into their natural history. AB - The authors report their experience with 17 cases of cystic hygroma diagnosed in utero over a period of 6 years and followed to early infancy. Attempts were made to determine which ultrasonographic features were significant in predicting the outcome of this condition. The intrauterine course of the 6 fetuses with a normal karyotype and the 11 fetuses with Turner's syndrome or another form of aneuploidy was analysed to determine whether the size of the hygroma or the presence of septation or nonimmune hydrops could be used to predict the eventual outcome of the pregnancy. An association between the presence of septation and outcome was not demonstrated, but there was a strong association between septation and aneuploidy. Septate lesions were present in 6 of the 10 fetuses with Turner's syndrome and only 2 of the 6 fetuses with a normal karyotype. In this series the most significant features indicating a favourable outcome were the size of the hygroma (no fetus in which the hygroma had a diameter greater than 6 cm survived) and the change in size from the time of diagnosis until 24 weeks' gestation. Of the three fetuses in which the hygroma did not regress by 24 weeks, two died in utero. PMID- 1450971 TI - Ultrasonographic findings in the anterior segment of the eye obtained with a nondedicated unit. AB - Many abnormalities of the anterior segment of the eye can be detected by ultrasonography (US), and associated anomalies of the posterior segment that are difficult to detect clinically may also be demonstrated by this modality. A total of 48 patients with ultrasonographically detectable abnormalities in the anterior segment were examined with real-time high-resolution US; 51 abnormalities were demonstrated. The most common problems were cataract (19 cases), intraocular lens implant (10), dislocated lens (9) and tumour (8). In addition, 23 abnormalities of the posterior segment of the eye were found. Six of the lesions in the posterior segment were obscured by those in the anterior segment and could be detected only by US. PMID- 1450972 TI - Varicocele embolization through competent internal spermatic veins. AB - Transvenous embolization has gained wide acceptance as a primary therapeutic technique in the management of varicocele. In most cases incompetence of the internal spermatic vein is the main cause of the disorder. In 18 of 165 patients treated with embolization, venography demonstrated competence of the internal spermatic vein; the varicocele was due to incompetence of some other anastomotic connection to the vein or the pampiniform plexus. The finding of valvular competence during embolization in a patient with clinical or ultrasonographic evidence of varicocele should not lead to termination of the procedure; instead, a concerted effort should be made to cross the valve to allow therapeutic embolization. PMID- 1450973 TI - Metastatic neuroblastoma presenting as a mandibular mass. AB - Neuroblastoma is the third most common type of cancer seen in children, after leukemia and tumours of the central nervous system. Although bony metastasis to the skull and the orbits has been well described, metastasis to the mandible is exceptional; 32 cases have been reported. Two more are presented here, along with a short review of the topic emphasizing the radiographic features and the differential diagnosis. PMID- 1450974 TI - The computed tomographic appearance of subcutaneous nodules occurring in metastatic neuroblastoma. AB - The authors report a case of subcutaneous nodules in a 2-month-old girl with metastatic neuroblastoma; the appearance of the nodules in computed tomography scans is described. Such nodules are sometimes overlooked by clinicians and radiologists, even though they almost always occur in disseminated disease. In patients with neuroblastoma and other neoplasms subcutaneous nodules may be an easily accessible source of samples for histopathologic examination. PMID- 1450975 TI - Computed tomographic detection of skeletal muscle calcifications in rhabdomyolysis. AB - The authors report a case of rhabdomyolysis with extensive calcification of the paravertebral muscles secondary to ingestion of desipramine hydrochloride, a tricyclic antidepressant. Computed tomography (CT) and isotope scanning were performed, and pathological confirmation of the condition was obtained. The extent of the calcification was probably due to the administration of supplementary calcium to correct hypocalcemia. The authors discuss the correlation between the CT and isotope scan findings. PMID- 1450976 TI - Angiography of a bronchial carcinoid tumour. AB - The author describes a patient in whom a bronchial carcinoid tumour was demonstrated preoperatively only by bronchial arteriography. The reported arteriographic characteristics of such a lesion include hypertrophy of the bronchial artery, a tumour blush and the apparent absence of venous drainage. PMID- 1450977 TI - Hemorrhagic colitis caused by Escherichia coli O157:H7--unusual ultrasonographic and computed tomography findings. AB - Hemorrhagic colitis due to Escherichia coli O157:H7 occurs sporadically but widely throughout North America. Radiographically this condition may mimic ischemic colitis, inflammatory bowel disease, acute appendicitis or appendiceal abscess. Correlation of radiologic and clinical findings is required to ensure diagnostic accuracy and avoid unnecessary surgical intervention. PMID- 1450978 TI - Ultrasonography of foreign-body tenosynovitis. AB - A patient presented with cellulitis of the hand 4 weeks after she was injured by sea urchin spines. Ultrasonography proved useful in identifying three small fragments of spine and suggested tenosynovitis. This method should be considered the imaging technique of choice for wounds of the hand when foreign bodies are suspected. PMID- 1450979 TI - Residents' corner. Answer to case of the month #16. Balkan nephropathy. PMID- 1450980 TI - Planning a safe technique for embolization of pseudoaneurysms of the inferior gluteal artery. PMID- 1450981 TI - [Study in the anuran amphibian Xenopus laevis, some blood characteristics and nitrogen excretion based on changes in the water osmolarity]. AB - The pH, the osmolality and the urea and ammonia concentrations in blood, as well as the net urea and ammonia excretions, were studied in the amphibian Xenopus laevis exposed for several weeks to increased osmotic pressure (OP) of the ambient water, as a result of the addition of either NaCl or mannitol to the water. The pH and the ammonia concentration of the blood were independent of the variations of the ambient osmolarity. On the contrary, the blood osmolality and its urea concentration increased markedly when the ambient OP was augmented. The increase of ambient OP by NaCl addition to the medium augmented the urea net excretion and slightly decreased the ammonia excretion. When the increase of ambient OP resulted from the addition of mannitol in the water, excretions of urea and ammonia became negligible. PMID- 1450982 TI - [Taste thresholds and above-threshold responses to fructose solution in relation to diet in Callitrichidae primates]. AB - Taste thresholds and consumption responses to above-threshold concentrations of fructose solutions were determined in eight callitrichid primate species using the "two-bottle preference test". Although taste thresholds are relatively similar across species, above-threshold responses may differ considerably between marmosets and tamarins. As fructose concentration increases, the rate of consumption increases less for most marmoset species (Cebuella and Callithrix spp.) than for Goeldi's monkey (Callimico) and tamarins (Saguinus and Leontopithecus spp.). It is proposed that distinct shapes of the curves illustrating these responses characterize species in terms of global taste system adaptations to different diets. PMID- 1450983 TI - [Binocular coordination during reading]. AB - Is there an effect on binocular coordination during reading of oculomotor imbalance (heterophoria, strabismus and inadequate convergence) and of functional lateral characteristics (eye preference and perceptually privileged visual laterality)? Recordings of the binocular eye-movements of ten-year-old children show that oculomotor imbalances occur most often among children whose left visual perceptual channel is privileged, and that these subjects can present optomotor dissociation and manifest lack of motor coordination. Close binocular motor coordination is far from being the norm in reading. The faster reader displays saccades of differing spatial amplitude and the slower reader an oculomotor hyperactivity, especially during fixations. The recording of binocular movements in reading appears to be an excellent means of diagnosing difficulties related to visual laterality and to problems associated with oculomotor imbalance. PMID- 1450984 TI - [Stimulation of the prostate growth in rats by milk casomorphins]. AB - Thymidine kinase activity of the ventral prostate from adult rats could be stimulated by administration to the animal of casomorphin or casomorphin (morphiceptin). On the other hand addition of both drugs to the culture medium of prostatic cells from immature rats enhanced the cells growth. In both cases, morphiceptin was more efficient than casomorphin. These results suggest than casomorphins have other properties than their morphinomimetic effects previously described. PMID- 1450985 TI - [Contribution of "bobbed" phenotype to the magnification of ribosomal DNA in Drosophila melanogaster]. AB - Phenotype and magnification of two bobbed mutations allelic to the XNO region were studied at various temperatures. Results showed that magnification increases with increased severity of bobbed phenotype in that the reversion of the bbT6 allele is the same at high and low temperature whereas the thermosensitive bbP5 allele shows increased reversion at high temperature. Temperature shift experiments carried out during the development of premagnified males show that magnification which is followed by selection stage occurs during embryogenesis. PMID- 1450986 TI - [Molecular and cellular action of butyrate]. AB - Butyrate has a dramatic effect on transformed cells in culture. This effect disappears as soon as butyrate is removed from the medium. The other short chain fatty acids are much less effective. Butyrate produces an arrest of cell proliferation at the early G1 phase of the cell cycle. The effect is very general and may be used for cell growth synchronization. This compound increases the expression of the c-fos oncogene and inhibits the expression of c-myc in all phases of the cell cycle. Butyrate modulates the expression of several genes. In general it induces the expression of markers of cell differentiation. Many studies have been devoted to hemoglobin synthesis which is induced in erythroleukemia cells. In general it induces the synthesis of embryonic and of fetal hemoglobin, and delays and even suppresses the switch to adult hemoglobin, which could be useful for the treatment of sickle cell anemia and beta thalassemia. This effect of butyrate seems to require specific DNA regulatory sequences. Butyrate induces the synthesis of alkaline phosphatase, placental and intestinal isozymes, especially in cells where these syntheses are ectopic. It has the same effect on peptidic hormone syntheses and also on receptors of thyroid hormone and insulin. It stimulates their synthesis in cells which are poor in receptor and inhibits the synthesis in cells which have high amounts of these receptors. The use of antibiotics and of the run on method strongly suggest that butyrate acts at the transcriptional level. Butyrate inhibits the induction of proteins, including enzymes, by steroid hormones as has been shown for the induction of tyrosine aminotransferase by glucocorticoids, of ovalbumin and transferrin by estradiol in chick oviduct. Butyrate strongly alters cell morphology, usually it produces an enlargement of the cells with formation of protrusions. In HTC cells alteration of nucleoli and of the nuclear shape are observed. All these alterations are reversible and the cells recover the normal morphology upon removal of butyrate. These alterations result at least partly from modifications of the cytoskeleton: induction of vimentin and cytokeratin, formation of microfilaments, of microtubules and of actin fibers. The external matrix is also modified, as are the cell surface glycoproteins, and gangliosides. Most of these alterations are consistent with the loss of transformation characteristics of the cell. The mechanism of action of butyrate has been studied by many authors. It has been well established that butyrate induces an hyperacetylation of histones by inhibiting histone deacetylases, which is consistent with its stimulatory effect on gene expression.4+ and would require transacting proteins. The use of butyrate in therapeutics would require the synthesis of new molecules including butyrate but more active and metabolized at a slower rate. Several such molecules have been synthesized: monobutyrate 3 (or 6) monoacetate glucose, pivalyloxymethyl-butyrate. The use of such molecules in human therapeutics has been suggested, especially in hematology (sickle cell anemia, beta thalassemia) and in cancerology. PMID- 1450987 TI - [Demonstration of cerebral lateralisation disorder in autistic children: study of auditory reactivity by transcranial pulsed Doppler]. AB - Transcranial Doppler Ultrasonographic recordings of the middle cerebral arteries were performed on children with autistic behavior (AUT), compared to retarded children without autistic behavior (NON-AUT) and normal children (NOR). Blood flow measurements (resistance index) were performed at rest and during auditory stimulations. Compared to NOR and NON-AUT, significant differences of the resistance index were found in AUT on the left side, thus suggesting differences in metabolic mechanisms evoked by auditory stimulations. This result confirms the hypothesis of abnormal development of cerebral lateralization in autism. PMID- 1450988 TI - [Relation between the change of slope of heart rate and second lactic and ventilatory thresholds in muscular exercise with large load]. AB - The time-course of heart rate, blood lactate, and ventilatory gas exchange was studied during an incremental exercise test on cycloergometer in order to ascertain whether heart rate deflection occurred at the same load as the second lactate S[La]2) and ventilatory (SV2) thresholds. Twelve moderately trained subjects, 22 to 30 years old, participated in the study. The initial power setting was 30 W for 3 min with successive increases of 30 W every min except at the end of the test where the increase was reduced to 20 and 10 W.min-1. Ventilatory flow (VE), oxygen uptake (VO2), carbon dioxide production (VCO2, ventilatory equivalents of O2 (EO2 = VE/VO2) and CO2 (ECO2 = VE/VCO2), and heart rate (HR) were determined during the last 20 s of every min. Venous blood samples were drawn at the end of each stage of effort and analyzed enzymatically for lactate concentration ([La]). The HR deflection, S[La]2, and SV2 were represented graphically by two investigators using a double blind procedure. Following the method proposed by Conconi et al. 1982, the deflection in HR was considered to begin at the point beyond which the increase in work intensity exceeded the increase in HR and the linearity of the work rate/HR relationship was lost. S[La]2 corresponded to the second breaking point of the lactate time-course curve (onset of blood lactate accumulation) and SV2 was identified at the second breaking point in the increase in VE and ventilatory equivalent for O2 uptake accompanied by a concomitant increase in ventilatory equivalent for CO2 output. We observed that the deflection point in HR was present only in 7 subjects. The work load, VO2, HR, and [La] levels at which heart rate departed from linearity did not differ significantly from those determined with S[La]2 ans SV2. The VO2 and HR values at HR deflection point were significantly correlated with those measured at S[La]2 and SV2. It is concluded that deflection in heart rate does not always occur, and when it does, it coincides with the second lactate and ventilatory gas exchange thresholds. It can thus be used for the determination of optimal intensity for individualized aerobic training. PMID- 1450989 TI - [Detection of the deletion of interferon-alpha and beta genes in lymphoblastoid cells by PCR]. AB - The HuIFN-alpha and beta genes were examined by the PCR method in the 11 human lymphoblastoid cell lines. The results showed that the homozygous deletion of HuIFN-alpha and beta genes was detected in 5 of 11 cell lines and in 5 of 11 cell lines, respectively. The deletions of both the HuIFN-alpha and beta genes were observed in 4 of 11 cell lines. One T cell leukemia cell line deleted only HuIFN alpha gene, while the other T cell leukemia line deleted only HuIFN-beta gene. This suggests that the deletions of HuIFN-alpha and beta genes may be related the development of leukemia or lymphoma. PMID- 1450990 TI - [Pain: physiopharmacological aspects]. PMID- 1450991 TI - [Current data on the exploration and the evaluation of clinical pain]. AB - Pain is a complex, multidimensional and multifactorial neuropsychological phenomenon with sensory-discriminative, affective, cognitive and behavioral components. Issues on pain assessment are related to the objective evaluation of a subjective phenomenon. Different levels of evaluation are to be considered. Some methods like visual analogue scale, numerical scale and verbal permit a global pain estimation. The aim of other methods like the McGill Pain Questionnaire is a quantitative and qualitative evaluation of the sensory and affective pain components. The measure of objective behavioral changes is an interesting approach, but at the present time there is no valid, simple and commonly used method. There is also a need for methods permitting a better exploration of a pain, and in particular a selective evaluation of organic and functional factors. The limits of psychological factors evaluation are reported. PMID- 1450992 TI - [Targeting of tumor cells by low density lipoproteins: principle and use of ellipticin derivatives]. AB - Cells acquire cholesterol via de novo synthesis and high affinity receptor mediated uptake of low-density lipoprotein (LDL). Some tumor tissues display increased receptor-mediated uptake of LDL as compared with the corresponding normal tissues. This increased LDL receptor activity is unexplained: a high cholesterol demand for cell growth or a mechanism directly linked to cell transformation. LDL has therefore been proposed as a potential carrier for chemotherapeutic agents. Various methods have been used to incorporate antineoplastic lipophilic drugs into LDL. The resultant drug-LDL complexes have been shown to be cytotoxic towards tumor cells in vitro, via the LDL receptor dependent pathway. However little is now on the in vivo fate of this complex. We described the incorporation of lipophilic derivatives of ellipticine into LDL by a fusion or facilitated transfer technique between drug containing microemulsions and LDL. The drug-LDL complex expressed similar metabolic activity, in vitro and in vivo, than native LDL. Initial experiments with melanoma B16 tumor-bearing mice suggest that LDL may be a potential drug carrier in the treatment of malignant diseases. The knowledge of the molecular mechanism of the expression of the LDL receptor in tumor cells and the ability to downregulate the LDL receptor in the normal tissues, will define the application field of this targeting approach. PMID- 1450993 TI - [Antitumor photochemotherapy: biochemical bases, therapeutic uses and perspectives]. AB - The photodynamic therapy of tumors (PDT) is a recent and promising technique for the treatment of tumors which can be reached by the light (directly or by endoscopic illumination). Excellent results are now obtained with hematoporphyrin derivatives such as Photofrin II, provided the concerned tumors are small and well delimited. Porphyrins are transported in blood mainly by lipoproteins, and the low density lipoprotein (LDL) receptor-mediated pathway is probably one of the important factors involved in the selective accumulation of porphyrins by tumor tissues, as cancer cells generally express much more LDL receptors than normal cells. In the present paper, after a brief presentation of the biochemical basis of the light-dependent cytotoxicity of porphyrins, we shall examine the role of lipoproteins, especially LDL, in the transport and the cellular uptake of these compounds. We shall also present recent approaches for the improvement of the PDT efficiency. PMID- 1450994 TI - Dentistry and the European community--1992 and all that! PMID- 1450995 TI - A classification of residential neighbourhoods (ACORN) in relation to dental health and dental health behaviours. AB - Five-year-old children in two district health authorities in the North Western Region of England were examined during 1989-90. Questionnaires were issued to parents to determine whether dental health and related behaviours were associated with socio-economic status. Parents of 1858 children in Salford (response rate = 78 per cent) and 1691 in Trafford (response rate = 81 per cent) returned the questionnaires. Their replies were analysed by dividing the children into a hierarchy according to a classification of residential neighbourhood (ACORN). Significantly fewer in the highest of three Divisions in both districts had suffered from toothache and had undergone a general anaesthetic to have teeth extracted. They were also more likely to have had their teeth brushed with toothpaste by their first birthday and to have visited the dentist by their second. Because ACORN had detected these differences in dental health related behaviour it was possible to identify localities towards which dental health promotion activities can be directed. PMID- 1450996 TI - Loss of the first permanent molar and caries experience of adjacent teeth. AB - The caries experience of the occlusal and distal surfaces of the second premolars and the occlusal and mesial surfaces of the second permanent molars was examined in four groups of subjects aged 19-20 years. Group 1 comprised subjects with first permanent molars present, Group 2 subjects with early loss of the first permanent molar (before the age of 11-12 years), Group 3 subjects with late loss of the first permanent molar (after 11-12 years but before 15-16 years) and Group 4 included a combination of Group 2 and Group 3. Loss of the first permanent molar was associated with increased caries or restorations in the occlusal surfaces of adjacent teeth, but reduced caries or restorations in the proximal surfaces of adjacent teeth. Early loss of the first molar was associated with significantly greater caries or restoration experience in proximal surfaces than late loss, but no difference was detected for occlusal surfaces. PMID- 1450997 TI - The prevalence of developmental defects of enamel in 15-16-year-old children residing in three districts (natural fluoride, adjusted fluoride, low fluoride) in the north east of England. AB - Developmental defects of enamel were assessed in 15-year-old children born and continuously resident in three communities in the north east of England. In naturally fluoridated Hartlepool (F = 1.0-1.3 ppm), artificially fluoridated Newcastle (F = 1.0 ppm) and non-fluoridated Middlesbrough (F < 0.2 ppm) 361, 356 and 376 children respectively were examined. Conventional clinical recording and a photographic technique where colour slides are assessed at random were used and compared. Scoring in both assessments was done by using a modified version of both the Murray and Shaw index and the developmental defects of enamel index. In the clinical assessment more white lines and diffuse opacities were found in the fluoridated areas than in the non-fluoridated area. More opacities were recorded using the photographic assessment than with the clinical assessment, but a similar trend of an increased prevalence of white lines and diffuse opacities was observed using the photographic method. Overall, there was only a small increase in the prevalence of milder forms of enamel defects in fluoridated compared with non-fluoridated areas. PMID- 1450998 TI - A programme of preventive dentistry in field conditions carried out in Glasgow, Scotland. AB - A caries-preventive regime comprising fluoride supplementation in age-related doses, three monthly acid-phosphate-fluoride applications, fissure sealing of deciduous and first permanent molars and chair-side dental health education, had been proved cost-effective in a single health centre setting. It was therefore expanded to a community-wide project in the Greater Glasgow area. This study describes the coverage achieved by the scheme, the demographic details of the children involved, and measured the dental health benefits accrued by the participants. The children received an annual dental examination and, to assess the effects of the programme, the records of 310 subjects who had attended three annual examinations were used. The deft and defs reductions ranged from 60 to 6.5 per cent and 58.8 to 9.6 per cent respectively, and equivalent DMFT and DMFS reductions ranged from 11.1 to 0 per cent, and 33.3 to 16.7 per cent respectively. Previously, deft reductions of 63.7 to 86.2 per cent, and defs reductions of 77.6 to 92.6 per cent had been reported (Stephen et al., 1983). In contrast, the corresponding deft and defs reductions achieved in this project were only up to 16.7 and 9.6 per cent respectively. The programme was most beneficial for children who had reached the age of three years after two year's participation in the scheme. The dental health benefits accrued by those receiving the preventive programme appear to be inversely proportional to its size. Therefore it represents an important example of the reduction of a preventive agents' effectiveness when used under field conditions, as opposed to those of controlled clinical trials. PMID- 1450999 TI - A comparison between commercial kits and conventional methods for enumeration of salivary mutans streptococci and lactobacilli. AB - Mutans streptococci (ms) and lactobacilli levels were determined by conventional and commercial dip-slide methods in three groups of young subjects, aged 5-6 years (93 subjects), 12-13 years (78 subjects) and 18-20 years (81 subjects). Using the same paraffin-stimulated saliva samples, ms and lactobacilli were estimated by conventional viable counts on modified mitis-salivarius agar (MSB) and Rogosa agar plates, and by inoculation of Dentocult SM and Dentocult LB dip slides (Orion Diagnostica, Finland). The salivary ms and lactobacilli counts obtained from conventional agar plates were significantly correlated (P < 0.0001) with the dip-slide estimates of these organisms (Kendal Tau = 0.56, 0.71 respectively). Subjects in Group 2 showed the highest proportion (77 per cent) of individuals with salivary ms levels above 2.5 x 10(5) cfu/ml saliva; 99 per cent of that group had detectable levels of lactobacilli. Significantly different median salivary ms and lactobacilli levels were demonstrated between all groups except for lactobacilli levels between Groups 2 and 3. These dip-slide tests provided suitable and simple methods for screening salivary lactobacilli and ms levels which may have a useful role in the assessment of caries risk. PMID- 1451000 TI - A multivariate model to predict caries increment in Montreal children aged 5 years. AB - A study was carried out in Montreal (Canada) to predict caries development over the period of one year in primary teeth of kindergarten children (mean age 5 years 8 months +/- 4 months) living in a non-fluoridated area. The 302 children were examined at school on two occasions, one year apart. At the first examination selected predictors were collected: caries experience, salivary S. mutans and lactobacilli, buffer capacity, debris index, parents' education, fluoride consumption and family structure (one or two parents). Regression analysis was performed to select the significant factors. A total of 143 children developed new caries over the study period; the mean increment for the whole group was 2.1 dmfs. Sensitivity (Sn) and specificity (Sp) were calculated for each predictor and for the final model. The best model comprised only two factors, caries experience and lactobacillus. This could identify 81.8 per cent of children who would develop new caries during the next 12 months (Sn) and 77.4 per cent of those who would not (Sp). Among the single predictors caries experience alone reached 78.3 per cent for sensitivity and 77.4 per cent for specificity. None of the other predictors, except parents' education, was very good at predicting caries increment over one year. PMID- 1451001 TI - Factors affecting dental attendance among school leavers and young workers in Greater Manchester. AB - The aim of this study was to investigate those factors which could influence adolescents in their dental attendance habits. Discussion groups were formed with school pupils in their final school year and with Youth Training Scheme trainees who had been working for six months or more. Fourteen discussions, involving 97 adolescents, were carried out and recorded on tape. Analysis of these tapes permitted comparison of the responses of the school leavers and the trainees which revealed some recurring themes. No major differences were found between the adolescents in their views on dental attendance before and after leaving school. Many respondents said that they had been able to decide for themselves about going to the dentist since they were 12, 13 or 14 years old, well before school leaving time. A low perception of need and a high level of confidence in self care were widely reported and these tended to reduce the likelihood of attendance. The desire to maintain or produce a good dental appearance was frequently given as the main motive for attending the dentist. PMID- 1451002 TI - Dental attendance patterns among mothers and their children in an area of social deprivation. AB - Dental attendance behaviour was recorded for 358 children aged 5-6 and 10-11 years and their mothers living in a socially deprived area of south Manchester. Information obtained by questionnaire was verified by the local dentists concerned. Forty-four per cent of mothers and 61 per cent of children had attended a dentist in the previous 12 months. The mothers' attendance was a good predictor of children's attendance, although a substantial proportion of mothers who did not attend the dentist themselves did ensure the attendance of their children. PMID- 1451003 TI - Factors determining satisfaction with dental care. AB - The objective of the present study was to study satisfaction with previous dental care in a Swedish population aged 45-69 years. The relationship between a number of factors and satisfaction with care was studied, and differences between people attending private and public dental clinics were examined. The data were collected by an anonymous questionnaire. A multivariate analysis showed that reported satisfaction with previous dental care depended primarily on three factors; treatment by the dentist of choice, chewing ability and contentment with their own dental conditions. PMID- 1451004 TI - Presidential address to the British Association for the Study of Community Dentistry, Cardiff, March 1992. PMID- 1451005 TI - Calcium involvement in free radical effects. PMID- 1451006 TI - Assessment of bone formation by biochemical markers in metabolic bone disease: separation between osteoblastic activity at the cell and tissue level. AB - In this study , serum levels of classical serum markers of bone formation [carboxyterminal propeptide of procollagen type I (S-PICP), bone Gla protein (S BGP)], and total alkaline phosphatase (S-AP)) were related to the calcium kinetic index of whole skeletal mineralization rate (m) by regression analysis in a variety of metabolic bone diseases. For each disease, the regression coefficient (r) as well as the fraction: standard error of estimate/mean dependent variable (SEE/Y) were determined. In a group of 19 normals, only the regression of S-PICP on m reached significance (r = 0.53, P < 0.02, SEE/Y = 0.44), whereas regressions of S-AP and S-BGP on m were nonsignificant. In a pooled material of high- and low turnover bone diseases without mineralization defects or spinal fracture [myxedema, thyrotoxicosis, and primary hyperparathyroidism (n = 48)], a highly significant positive regression of S-PICP on m was demonstrable (r = 0.50, SEE/Y = 0.63, P < 0.001). The regression coefficients obtained for S-BGP and S-AP were 0.74 (P < 0.001, SEE/Y = 0.41) and 0.42 (P < 0.01, SEE/Y = 0.55), respectively. When analyzing individual diseases in this group, significant differences among the three markers were detectable. In a group of 52 osteoporotics, S-PICP correlated significantly to m (r = 0.49, P < 0.001, SEE/Y = 0.50). Corresponding r-values for S-BGP and S-AP were 0.21 (NS) and 0.48 (P < 0.001, SEE/Y = 0.61), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451007 TI - Serum intact parathyroid hormone levels in elderly Chinese females with hip fracture. AB - Serum intact parathyroid hormone (PTH), 25 hydroxyvitamin D(25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), albumin, and ionized calcium were measured in 61 Chinese female patients with hip fracture and 61 control subjects. Hip fracture patients had low albumin, ionized calcium, and 250HD levels. Serum PTH and 1,25(OH)2D values were not different between the two groups. We conclude that although 250HD level in hip fracture patients is low, there is no evidence of secondary hyperparathyroidism, suggesting that the low 250HD levels may be a secondary phenomenon in response to the fracture. PMID- 1451008 TI - The relationship between ultrasound and densitometric measurements of bone mass at the calcaneus in women. AB - Broadband ultrasound attenuation (BUA) of the calcaneus predicts axial density in women and is decreased in women who sustain hip fractures. To determine the relationship between ultrasonic and densitometric assessments of bone mass at the same site, BUA and velocity of sound (VOS) were correlated with bone density as measured by dual energy x-ray absorptiometry (DXA) at the calcaneus in 64 Caucasian women aged 35-83 years. BUA, VOS, and bone density in these women decreased annually as a function of age by 1.0%, 0.3%, and 0.9%, respectively. Holding age, years since menopause, height and weight constant, BUA correlated with VOS (r = 0.74, P < 0.001), and calcaneal density correlated with BUA (r = 0.73, P < 0.001) and with VOS (r = 0.66, P < 0.01). The results indicate that both BUA and VOS measurements reflect density at the calcaneus, but suggest that they measure properties of bone other than density and different from each other. The assessment of these additional properties may be useful in the prediction of fracture risk. PMID- 1451009 TI - Caffeine has the capacity to stimulate calcium release in organ culture of neonatal mouse calvaria. AB - In view of the possible association between ingestion of caffeine (a constituent of coffee, tea, and several beverages) and osteoporosis, we have studied the effect of caffeine on bone resorption in vitro. Caffeine caused a dose-dependent increase of the spontaneous release of 45Ca from neonatal mouse calvarial bones. The effect of caffeine was less pronounced than that of parathyroid hormone (PTH), but of the same magnitude as that of theophylline, a structurally related methylxanthine. The enhancement of 45Ca release induced by caffeine and PTH was observed in 5 days culture. In 2 days culture, however, only PTH stimulated mineral mobilization. The delayed stimulatory effect of caffeine in long-term cultures was abolished by indomethacin and flurbiprofen. In indomethacin-treated bones, however, caffeine potentiated the stimulatory effect on 45Ca release induced by choleratoxin and forskolin. In contrast, caffeine did not potentiate 45Ca release stimulated by PTH. These data show that caffeine can stimulate calcium release from bone in vitro and that this effect is due to potentiation of a stimulatory action of a bone resorptive agonist acting via the adenylate cyclase-cyclic AMP system. PMID- 1451010 TI - Modulation of matrix vesicle enzyme activity and phosphatidylserine content by ceramic implant materials during endosteal bone healing. AB - This study examined effects of bone bonding and nonbonding implants on parameters associated with matrix vesicle-mediated primary bone formation, matrix vesicle alkaline phosphatase and phospholipase A2 specific activities, and phosphatidylserine content. Tibia marrow ablation followed by implantation of KG Cera, Mina 13 (bonding), KGy-213, or M 8/1 (nonbonding) was used as the experimental model. Postsurgery, matrix vesicle-enriched microsomes (MVEM) were isolated from implanted and contralateral limbs. MVEM alkaline phosphatase and phospholipase A2 were stimulated adjacent to bonding implants with similar, though reduced, effects contralaterally. Alkaline phosphatase exhibited slight stimulation in nonbonding tissue; phospholipase A2 was inhibited or unchanged in treated and contralateral limbs. Phosphatidylserine content of MVEM was differentially affected by the implant materials. Thus, MVEM are modulated by implant materials locally and systemically. The data demonstrate that the model is a biologically relevant diagnostic for assessing the tissue/implant interface, primary calcification is affected by implant materials, and implant-specific effects are detected in the contralateral unimplanted limb. PMID- 1451011 TI - Affinity of bone sialoprotein and several other bone and dentin acidic proteins to collagen fibrils. AB - Bone and dentin contain several kinds of mineral-binding proteins and cell attachment proteins. The authors examined the affinity of these proteins to type I collagen, a major matrix protein of the tissue. Bone sialoprotein (BSP), bone Gla protein (BGP), bone small proteoglycan II (PG II), osteonectin (ON), and dentin phosphophoryn (DPP) were labeled with fluorescein isothiocyanate and incubated with reconstituted type I collagen fibril. DPP, BGP, BSP, and PG II were absorbed significantly to the collagen fibril at physiological ionic strength with dissociation constants of 10(-6)-10(-7) M. BSP and PG II enhanced the fibrillogenesis of collagen. These acidic proteins can affect the surface properties of collagen fibril, and BSP, having the cell-attachment sequence Arg Gly-Asp, possibly mediates interaction between collagen fibril and cells. PMID- 1451012 TI - FT-IR microscopic mappings of early mineralization in chick limb bud mesenchymal cell cultures. AB - Chick limb bud mesenchymal cells differentiate into chondrocytes and form a cartilaginous matrix in culture. In this study, the mineral formed in different areas within cultures supplemented with 4 mM inorganic phosphate, or 2.5, 5.0, and 10 mM beta-glycerophosphate (beta GP), was characterized by Fourier-transform infrared (FT-IR) microscopy. The relative mineral-to-matrix ratios, and distribution of crystal sizes at specific locations throughout the matrix were measured from day 14 to day 30. The only mineral phase detected was a poorly crystalline apatite. Cultures receiving 4 mM inorganic phosphate had smaller crystals which were less randomly distributed around the cartilage nodules than those in the beta GP-treated cultures. beta GP-induced mineral consisted of larger, more perfect apatite crystals. In cultures receiving 5 or 10 mM beta GP, the relative mineral-to-matrix ratios (calculated from the integrated intensities of the phosphate and amide I bands, respectively) were higher than in the cultures with 4 mM inorganic phosphate or in the in vivo calcified chick cartilage. PMID- 1451013 TI - Acronyms in bone densitometry. PMID- 1451014 TI - Toxicity and pharmacokinetics of intravitreally injected ciprofloxacin in rabbit eyes. AB - To assess the toxicity of intraocular injection of ciprofloxacin, 22 New Zealand white rabbits received midvitreal injections of 100, 200, 400, 800 or 3200 micrograms of ciprofloxacin in 0.1 mL of distilled water (39 eyes) or 0.1 mL of distilled water only (5 eyes). The ocular pharmacokinetics of intravitreally injected ciprofloxacin was determined by aqueous humour and vitreous sampling 1, 2, 4, 8, 12, 18 or 24 hours after midvitreal injection of 100 micrograms of the drug in one eye each of 25 New Zealand white rabbits. The samples were analysed by means of a disc diffusion bioassay. No ocular damage was noted on ophthalmoscopy at any of the concentrations tested. Histologic study showed mild, transient vacuolation of the nerve-fibre layer in all eyes, including the control eyes, 2 hours after injection; at 24 hours no vacuolation was evident except at concentrations of 800 and 3200 micrograms, at which plexiform layer damage was evident. Peak aqueous and vitreous levels of ciprofloxacin were obtained at 1 hour (0.59 and 27.26 micrograms/mL respectively); the vitreous level fell to below 1.0 micrograms/mL 12 hours after injection. We conclude that intravitreally injected ciprofloxacin may be a safe and useful antibiotic in the treatment of aminoglycoside-resistant bacterial endophthalmitis. PMID- 1451015 TI - Ethmoidectomy decompression for the treatment of Graves' optic neuropathy. AB - When orbital decompression becomes necessary in Graves' optic neuropathy, medial wall decompression is a necessary component of the decompression procedure. The ethmoidectomy approach allows more direct visualization of the posterior ethmoids and sphenoids to effect maximum decompression. This is particularly important in cases in which computed tomography shows the medial rectus muscle to be enlarged posteriorly in the orbit. The procedure provides excellent visualization of the medial rectus. As with any medial wall decompression procedure, postoperative restriction of horizontal motility is a frequent complication, often necessitating more than one subsequent operation. The authors describe their experience with the procedure in 25 patients with Graves' optic neuropathy. PMID- 1451016 TI - Automated detection and quantification of venous beading using Fourier analysis. AB - Venous beading associated with diabetic retinopathy is currently assessed by means of subjective comparison to standard photographs from the modified Airlie House classification scheme. We describe a computerized grading scheme for venous beading. The algorithm, based on Fourier analysis of vessel width measurements, generates a venous beading index (VBI) for digitized colour fundus photographs. Colour photographs of local vessel segments about 1200 microns in length were evaluated by experienced graders. A comparison between the VBI and subjective grading showed good agreement. The mean VBI values across the four levels of clinical grading were significantly different (p = 0.000). Multiple comparison testing indicated that the VBI was able to significantly differentiate between all four categories except the "questionable" (grade 1) category (p < 0.05). We also found that progression of venous beading can be followed with the VBI. The results indicate that further development of automated grading of venous beading is warranted. PMID- 1451017 TI - Collagen shields: efficacy, safety and comfort in the treatment of human traumatic corneal abrasion and effect on vision in healthy eyes. AB - To study the efficacy, safety and comfort of porcine collagen shields in the treatment of traumatic corneal abrasion, patients with corneal abrasions that had occurred within 24 hours before examination were treated with either a collagen shield (18 patients) or tight patching (12 patients). There was no significant difference in the rate of healing or the proportion of corneas healed between the two groups. The collagen shield was significantly more comfortable than the patch (p < 0.05). After 1 hour of wear the collagen shield allowed useful vision (mean 20/100) in nine healthy volunteer subjects. Collagen shields may be of benefit in carefully selected cases of traumatic corneal abrasion. PMID- 1451018 TI - Role of tear secretory IgA in hard contact lens-related changes in the tarsal conjunctiva. AB - The role of tear secretory IgA in contact lens-related conjunctival changes was investigated in 40 subjects (80 eyes) who wore polymethyl methacrylate (PMMA) contact lenses and 10 subjects (20 eyes) who did not wear contact lenses. The eyes in the contact lens group had significantly higher tear IgA levels than the control eyes (p < 0.05). We were not able to demonstrate a relation between increased IgA levels and the presence of symptoms or duration of contact lens wear. Increased IgA levels were correlated to papilla formation in the contact lens group. A rise in tear IgA levels seems to be the first abnormal change related to papilla formation in patients who wear PMMA contact lenses. PMID- 1451019 TI - Cyclosporine in the treatment of nonmicrobial inflammatory ophthalmic disease. AB - Eighteen patients with severe, progressive nonmicrobial inflammatory ophthalmic disease (including five with intermediate uveitis, four with sympathetic ophthalmia and three with serpiginous choroiditis) that had not responded to conventional therapy were treated with cyclosporine. Three of the four patients with sympathetic ophthalmia responded quickly and maximally, and the fourth showed partial improvement. One patient, with several corneal graft failures in the right eye, started cyclosporine therapy after undergoing left corneal transplantation; at the last follow-up visit the graft had been clear for almost 3 years. The response was inconsistent in patients with other types of eye disease. In general, the drug was well tolerated; however, two patients stopped treatment because of unpleasant side effects. No serious or irreversible complications developed. The results suggest that cyclosporine therapy is useful in the treatment of sympathetic ophthalmia and in high-risk corneal transplantation. PMID- 1451020 TI - Ocular findings and visual evoked potential response in the Prader-Willi syndrome. AB - It has recently been suggested that aberrant misrouting of retino-geniculate cortical (RGC) projections, a finding previously noted only in albinism, may be an additional feature of the Prader-Willi syndrome. To determine the prevalence of ocular abnormalities in patients with the syndrome and to look for evidence of misrouted RGC projections by means of testing of the pattern-onset visual evoked potential (VEP) response, we examined 12 patients with Prader-Willi syndrome, 8 albino subjects and 5 healthy control subjects. Ocular findings in the first group included telecanthus (in five subjects), strabismus, nystagmus, foveal hypoplasia, visual field defects and cataract. However, the VEP asymmetry typically seen in albinism was not noted in any of the patients with Prader-Willi syndrome. Our findings do not support previous claims of abnormal optic nerve fibre decussation in Prader-Willi syndrome. PMID- 1451021 TI - Drug-induced fatal aplastic anemia following cataract surgery. AB - Aplastic anemia attributed to medications used in ophthalmology is rare. We report a fatal case that developed in a 73-year-old woman 7 weeks after cataract extraction performed under local anesthesia. Postoperative medications included a chloramphenicol-containing ointment, flurbiprofen sodium drops, prednisone acetate drops and orally given acetazolamide. It was felt that the aplastic anemia was related to therapy with chloramphenicol or acetazolamide or both. We recommend that the course of prophylactic antibacterial therapy after intraocular surgery be kept short, regardless of the preparation used. We urge caution in the choice and use of drugs known to be associated with aplastic anemia and recommend close monitoring of the hemogram. PMID- 1451022 TI - Influence of low-flow infusion and magnesium on tissue necrosis during regional ischemia in the canine myocardium. AB - Passive intracoronary perfusion of therapeutic agents has been used in the clinical setting to attenuate the effects of brief episodes of myocardial ischemia. The objective of this study was to assess the effects of low-flow coronary infusion with or without Mg2+ on tissue necrosis and cardiac hemodynamics after prolonged regional ischemia. In 33 anesthetized dogs (5 excluded during study), the left anterior descending coronary artery was occluded for 6 h. Dogs were assigned to three groups: the first group (n = 8) was subjected to 6 h coronary occlusion without low-flow perfusion (controls), the second group (n = 10) received a low-flow coronary infusion of Ringer's lactate (Mg(2+)-free), and the third group (n = 10) received a low-flow coronary infusion of Ringer's lactate plus Mg2+ sulfate (15 mM). Tissue necrosis was evaluated using tetrazolium staining and was normalized to the principal baseline predictors of infarct size including anatomic risk zone (microsphere autoradiography) and coronary collateral flow. In control hearts, infarct size comprised 51.1 +/- 4.1% of the risk zone (40.8 +/- 5.1% left ventricular cross sectional area (LV)). In the Mg(2+)-free and Mg2+ groups, risk zone size was 17.3 +/- 2.2 and 16.8 +/- 1.8% LV (p < 0.05 vs. controls), while infarct size was 23.1 +/- 3.1 and 24.9 +/- 8.1% (p < 0.05 vs. controls), respectively. Coronary collateral flow in the endocardium was similar for all of the experimental groups; however, hearts subjected to ischemia with low-flow perfusion of Ringer's lactate demonstrated significantly higher epicardial coronary collateral flow levels compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451023 TI - Renal adrenergic receptors: localization of [125I]prazosin binding sites along the microdissected rat nephron. AB - Norepinephrine stimulates renal tubular sodium reabsorption, probably through an alpha 1-adrenoceptor-mediated mechanism. Although the distribution of alpha 1 adrenoceptors in the kidney has been studied with autoradiography, the precise location of these receptors in isolated nephron segments is unclear. Using a microassay we determined the specific binding of [125I]iodoarylazidoprazosin ([125I]prazosin), a high specific radioactivity analog of the selective alpha 1 antagonist prazosin, to microdissected glomeruli and tubule segments. Specific binding of [125I]prazosin (3 nM) in the proximal convoluted tubule was time- and concentration-dependent, saturable, and reversible. In this segment the apparent KD by association and dissociation rate constants of [125I]prazosin binding was 0.47 nM, and the maximum receptor density was approximately 0.19 fmol/mm, or 720 fmol/mg protein. Binding specificity was verified in competition studies with excess (3 microM) unlabeled prazosin and probes for alpha 2- (yohimbine), beta- (propranolol), dopamine1- (SCH23390), and dopamine2- (S-sulpiride) receptors. [125I]Prazosin binding was inhibited significantly only by unlabeled prazosin. Mapping of prazosin binding along the nephron revealed that the highest density was in the proximal convoluted tubule, followed by the proximal straight tubule. Lesser binding was found in the thick ascending limb and in the distal convoluted tubule, whereas in the cortical and outer medullary collecting duct and in glomeruli, binding was not significantly different from zero.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451024 TI - Catecholamine-induced changes in vascular capacitance and sympathetic nerve activity in dogs. AB - The effects of three catecholamines, dopamine, epinephrine, and dobutamine, on the systemic circulation, especially on systemic vascular capacitance, were studied using cardiopulmonary bypass in dogs anesthetized with pentobarbital. Venous outflow was divided into three compartments: splanchnic, renal, and other; changes in systemic blood volume (SBV) were calculated from the changes in total venous outflow. To examine the contribution of sympathetic discharge to these vascular responses, sympathetic efferent nerve activity (SENA) from the ventral ansa subclavian nerve was recorded simultaneously. Experiments were done under three conditions: control, after baroreceptor deafferentation, and after hexamethonium injection with low and high doses of each catecholamine. During control and after baroreceptor deafferentation, dopamine- and epinephrine-induced changes in SBV were less than those after hexamethonium, and not significant except with low dose epinephrine. After hexamethonium, dopamine (200 micrograms/kg), epinephrine (10 micrograms/kg), and dobutamine (100 micrograms/kg) reduced SBV by 10.6 +/- 3.4, 13.1 +/- 1.7, and 1.9 +/- 0.3 mL/kg, respectively. Splanchnic outflow increased significantly with dopamine and epinephrine after hexamethonium. High dose dopamine and epinephrine significantly suppressed SENA to 38 +/- 9 and 15 +/- 6% of baseline, respectively. Low dose dopamine decreased arterial pressure and SENA. This suppression in SENA was attenuated but still observed after baroreceptor deafferentation. Dobutamine reduced SBV, but had no effect on SENA. These results suggest that dopamine and epinephrine primarily decrease SBV by venoconstriction in the splanchnic region, however, these effects are greatly modified by basal sympathetic discharge and changes in SENA and vascular tone. PMID- 1451025 TI - Regional venous outflow, blood volume, and sympathetic nerve activity during hypercapnia and hypoxic hypercapnia. AB - We examined the changes in systemic blood volume and regional venous outflow from the splanchnic, coronary, and other remaining vascular beds in response to acute hypercapnia or hypoxic hypercapnia in dogs, using cardiopulmonary bypass and a reservoir. Hypercapnia (PCO2 = 105 mmHg) (1 mmHg = 133 Pa) and hypoxic hypercapnia (PO2 = 23 mmHg, PCO2 = 99 mmHg) caused marked decreases in systemic blood volume of 14 +/- 3 and 16 +/- 3 mL/kg in spleen-intact dogs, and 3 +/- 2 and 10 +/- 2 mL/kg in splenectomized dogs, respectively. Splanchnic venous outflow increased by 12% at 3.5 min hypercapnia, whereas it decreased by 60% at 3.5 min hypoxic hypercapnia. Coronary venous outflow increased by 85 and 400% at 3.5 min hypercapnia and hypoxic hypercapnia, respectively. Sympathetic efferent nerve activity revealed a significant augmentation during hypoxic hypercapnia and a relatively smaller increase (30% of the response to hypoxic hypercapnia) during hypercapnia. Carotid and aortic chemoreceptor and baroreceptor denervation attenuated significantly the response of systemic blood volume to hypercapnia and hypoxic hypercapnia. The regional venous outflow responses to hypercapnia were not altered after chemodenervation, but those to hypoxic hypercapnia were significantly attenuated after chemodenervation. These results suggest that acute hypercapnia and hypoxic hypercapnia caused a marked decrease in vascular capacitance owing primarily to an increase in sympathetic efferent nerve activity via chemoreceptor stimulation. They also indicate that blood flow to the splanchnic vascular bed during hypercapnia increased (even though the cardiac output was constant), whereas it increased to the extrasplanchnic and coronary vascular beds during hypoxic hypercapnia. PMID- 1451026 TI - Diabetic type of cardiomyopathy in food-restricted rats. AB - We have demonstrated that food restriction that is associated with weight loss can produce a type of cardiac dysfunction similar to that produced by diabetes. As in diabetic atria, the food-restricted atria had a 2-fold increase in contraction force, rate of force development, and rate of force decline compared with controls. Both food-restricted and diabetic atria could tolerate anoxia better than controls. The contractile function of the whole perfused heart from the food-restricted rat was reduced, as in the case of the diabetic heart. As the left ventricular volume was increased, the left ventricular developed pressure and the rate of rise and fall in pressure were significantly reduced in both food restricted and diabetic hearts, compared with those of age- and weight-matched controls. The positive inotropic responses of atria and whole perfused heart to increasing concentrations of extracellular calcium were similarly altered in food restricted and diabetic hearts. The possible molecular mechanisms of these findings and some of the differences observed between food-restricted and diabetic hearts are discussed. PMID- 1451027 TI - The influence of calcium on ANF release in the isolated rat atrium. AB - We developed an in vitro model of the isolated, perfused rat atrium with which to examine the mechanisms linking muscular stretch to atrial natriuretic factor (ANF) secretion. It was shown that an increase in atrial pressure causing distension of the atria is associated with a rise in ANF secretion correlating with the degree of pressure load. Pressure-induced ANF secretion is enhanced by the calcium blocker nifedipine or omission of calcium from the perfusion buffer. The changes in atrial volume in response to a given pressure load are also more pronounced in the absence of calcium or following the addition of the calcium blocker. These data suggest that in nonbeating atria, stretch-induced ANF secretion does not rely on calcium influx. PMID- 1451028 TI - Evidence for an effector role of endothelin in closure of the ductus arteriosus at birth. AB - The ductus arteriosus is a special muscular shunt that in the fetus allows blood to bypass the unexpanded lungs. It closes rapidly after birth and this event is initiated by the physiologic rise in blood oxygen tension. Endothelin-1 has been proposed by us as a local mediator for oxygen after demonstrating that it is formed within the ductus and is a potent ductus constrictor. To confirm this possibility, we have now measured the release of endothelin-1 from the isolated ductus of near-term fetal lambs at different oxygen concentrations of the medium. In addition, using the same preparation, we have examined the effect on contractile tone of compounds interfering with the synthesis (phosphoramidon, 50 microM) and action (BQ123, 1 microM) of endothelin-1. We report that release of endothelin-1 from the ductus tends to increase with the oxygen concentration up to a value mimicking the neonatal condition. Phosphoramidon and, to a greater degree, BQ123 inhibit the contraction of the vessel to oxygen. These results implicate endothelin-1 as the effector agent for oxygen in the ductus and, by extension, assign to this peptide a critical role in the closure of the vessel at birth. PMID- 1451029 TI - Extracellular ATP stimulates elastase secretion from human neutrophils and increases lung resistance and secretion from normal rat airways after intratracheal instillation. AB - The effect of ATP on intracellular Ca2+ levels and elastase secretion in isolated normal human peripheral blood neutrophils was investigated as was its in vivo effect on lung resistance and mucous secretion. ATP (10(-5) M) increased [Ca2+]i from 61 +/- 3 to 165 +/- 15 nM in nonactivated neutrophils; elastase secretion was increased by 40% from nonactivated neutrophils but was unaffected in fMLP (10(-5) M) activated cells. Instillation of ATP (10(-5) and 10(-3) M) into the airways of brown Norway rats increased both lung resistance and secretion. These findings suggest that aerosolization of ATP into the cystic fibrosis-affected bronchial tree might be hazardous in terms of enhancement of parenchymal damage, which would result from neutrophil elastase release, and in terms of impaired respiratory lung function. PMID- 1451030 TI - Inhibition of chick embryo hepatic uroporphyrinogen decarboxylase by components of xenobiotic-treated chick embryo hepatocytes in culture. II. AB - A variety of xenobiotics, viz., 3,3',4,4'-tetrachlorobiphenyl (TCBP), sodium phenobarbital (PB), 3,5-diethoxycarbonyl-2, 4,6-trimethylpyridine (OX-DDC), and nifedipine, cause a decrease in uroporphyrinogen decarboxylase (UROG-D) activity, accompanied by uroporphyrin accumulation, in chick embryo hepatocytes in culture. In this study the activity of 17-day-old chick embryo hepatic UROG-D was determined by measuring the conversion of pentacarboxylporphyrinogen I to coproporphyrinogen I, and it was shown that a UROG-D inhibitor, previously reported to accumulate in TCBP-treated and PB-treated chick embryo hepatocytes in culture, also accumulates in OX-DDC-treated and nifedipine-treated chick embryo hepatocytes in culture. It was concluded that the accumulation of a UROG-D inhibitor provides an explanation for the UROG-D inhibition observed in this culture system with xenobiotics that cause uroporphyrin accumulation. Studies of the UROG-D inhibitory fraction isolated from the 10,000 x g, 40,000 x g, and 100,000 x g supernatant fractions of cultured chick embryo hepatocyte homogenate led to the conclusion that the UROG-D inhibitor is derived from a soluble component of the homogenate. PMID- 1451031 TI - M2 muscarinic ([3H]N-methyl scopolamine) binding in micropunches of rat ventricular myocardium: characterization and modification by progesterone. AB - A new technique is outlined for the characterization and quantification of M2 muscarinic binding sites (receptors) in micropunches (1 mm diam.), cut from slices (350 microns), of fresh cardiac tissue using the hydrophilic antagonist [3H]N-methyl scopolamine. The use of this water-soluble ligand allows us to label, and quantify, M2 receptors on the cell surface of intact cells contained within the micropunch. We believe that cardiac micropunches offer a simple but powerful approach to the investigation of membrane receptor regulation in tissue that largely retains the in vivo cytoarchitecture. Specific binding is reversible, stereospecific, saturable, of high affinity, and has the drug specificity typical of an M2 muscarinic receptor. In rat left ventricle, Bmax was 151.2 +/- 10.3 fmol/mg protein while KD was 1.0 +/- 0.1 nM. Nonspecific binding of the ligand was very low, varying from 2.8% (at 0.27 nM) to 7.7% (at 3.58 nM). This micropunch assay was used to determine that progesterone can compete with the muscarinic ligand for the M2 receptor in vitro (IC50 = 50 x 10(-6) M). The steroids estradiol and testosterone, as well as ouabain, were without effect. Progesterone inhibited [3H]N-methyl scopolamine binding competitively (KD reduced from 1.9 to 4.3 nM) without affecting the rate of association of the ligand. However, progesterone induced a rapid dissociation of the ligand from its receptor. We conclude that the micropunch assay described here is suitable for the continued study of sex hormone effects on cardiac function. PMID- 1451032 TI - Impact of increased infarct transmurality on remodeling and function during healing after anterior myocardial infarction in the dog. AB - To determine the impact of greater infarct transmurality on changes in left ventricular remodeling and function after acute anterior myocardial infarction, serial topographic and functional parameters (two-dimensional echocardiograms) and hemodynamics over 6 weeks, and postmortem topography (planimetry) at 6 weeks, were measured in chronically instrumented dogs randomized to standard coronary artery ligation (group 1) or a modified lower ligation plus collateral obliteration to decrease collateral inflow and increase transmurality (group 2). At 6 weeks, postmortem scar size and collagen were similar in the two groups, but group 2 had greater transmurality associated with more necrosis relative to area at risk, Q waves, infarct expansion, thinning, regional bulging, and cavity dilatation. Over the 6 weeks, group 2 showed more early expansion, late thinning and regional bulging in the short axis, larger diastolic and systolic volumes, and more apical aneurysmal bulging in the long-axis, reflecting more topographic deterioration. More important, group 2 showed greater regional and global left ventricular dysfunction over 6 weeks, lower ejection fraction at 2 days with further decrease over 6 weeks, and more left ventricular thrombus, ventricular arrhythmias, and deaths. In addition, transmurality correlated with the severity of remodeling and dysfunction. The findings indicate that transmurality is a major determinant of remodeling and left ventricular dysfunction during healing after anterior infarction. PMID- 1451033 TI - 85Sr uptake by the chick embryonic heart: effect of high doses of isoproterenol. AB - The aim of the present study was to establish whether intraamnial administration of toxic doses of isoproterenol to chick embryos increases cardiac accumulation of strontium, the homologue element of calcium. It has been shown that the ability of embryonic tissues (blood, heart, and liver) to accumulate 85Sr decreases significantly during ontogeny. Administration of isoproterenol to chick embryos did not elevate the concentration of 85Sr in the heart. It seems, therefore, that isoproterenol-induced developmental changes in the chick embryonic myocardium are not necessarily due to intracellular calcium (as measured by 85Sr) overload. PMID- 1451034 TI - Modulatory effect of steroid hormones on GnRH-induced LH secretion by cultured rat pituitary cells. AB - The purpose of the present experiments was to examine the short- and long-term effects of estradiol-17 beta (E2), progesterone (P), and 5 alpha dihydrotestosterone (DHT), alone and in combination, on the gonadotrophin releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion, using an ovariectomized rat pituitary cells culture model. After 72 h in steroid-free medium, pituitary cells were further cultured for 24 h in medium with or without E2 (1 nM), P (100 nM), or DHT (10 nM). Cultures were then incubated for 5 h in the absence or presence of 1 nM GnRH with or without steroids. LH was measured in the medium and cell extract by radioimmunoassay. The results show that the steroid hormones exert opposite effects on the release of LH induced by GnRH, which seems to be dependent upon the length of time the pituitary cells have been exposed to the steroids. In fact, short-term (5 h) action of E2 resulted in a partial inhibition (64% of control) of LH release in response to GnRH, while long term (24 h) exposure enhanced (158%) GnRH-induced LH release. Similar results were obtained with DHT, although the magnitude of the effect was lower than with E2. Conversely, P caused an acute stimulatory action (118%) on the LH released in response to GnRH and a slightly inhibitory effect (90%) after chronic treatment. GnRH-stimulated LH biosynthesis was also influenced by steroid treatment. Significant increases in total (cells plus medium) LH were observed in pituitary cells treated with E2 or DHT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451035 TI - Intrafibre distribution of succinate dehydrogenase in cat tibialis anterior motor units. AB - Using isolated ventral root filament stimulation and glycogen depletion techniques, 14 motor units from the cat tibialis anterior were studied. Based on their mechanical properties, the units were classified as either slow-fatigue resistant, fast-fatigue resistant, fast-fatigue intermediate, or fast-fatigable. Quantitative histochemical and computer assisted image analysis techniques were used to determine the activity of succinate dehydrogenase in a population of fibres in each unit. In addition, the intrafibre distribution of succinate dehydrogenase activity was measured in those same fibres by calculating the enzymatic activity of circumferential layers every 0.5 microns starting from the fibre edge to its centre. It was established that enzymatic activity and radial distance were linearly related in the fibres. A range in succinate dehydrogenase activity (mean coefficient of variation, 29%) was observed among the fibres of a unit. In contrast, the intrafibre distribution of that activity was rather consistent (mean variation, 4%) across the fibres of a unit. Further, the intrafibre distribution was similar among the fibres of units classified as the same type. However, the intrafibre distribution was disparate among the different unit types. These data suggest that the intrafibre distribution of mitochondrial enzymes may contribute to the mechanical properties of a motor unit. In this regard, a hypothesis is proposed that describes how the absolute activity of a mitochondrial enzyme, and the intrafibre distribution of that activity, may interactively contribute to the fatigue resistance of a unit. PMID- 1451036 TI - Reversibility of renal tubular dysfunction in streptozotocin-induced diabetes in the rat. AB - Enzymuria and specific proteinuria were examined over a period of 19 days in 4 groups of 5 rats: a control group, a nondiabetic polyuric group, a group of streptozotocin-induced diabetic rats treated with insulin as of the 10th day after the injection of the drug, and a similar group of untreated diabetic rats. Increased urinary excretion of beta-N-acetyl-D-glucosaminidase, lactate dehydrogenase, and alanine aminopeptidase was observed shortly after the induction of diabetes. It was partly or totally reversible following insulin treatment. Nondiabetic polyuria had a slight effect on the excretion of alanine aminopeptidase only. The urinary excretion of beta 2-microglobulin also rapidly increased after the onset of diabetes to a level approximately 50 times the control values. This effect was largely reversible with insulin treatment and was absent in the nondiabetic polyuric group. A small but significant 3-fold increase in albumin excretion was also noted but was not affected by insulin treatment. We conclude that streptozotocin-induced diabetes causes an early tubular dysfunction that is unrelated to polyuria and is reversible upon insulin treatment. This tubular dysfunction is best revealed by the urinary excretion of the low molecular weight protein beta 2-microglobulin. Our results suggest that it would be of interest to further examine the usefulness of sensitive markers of tubular dysfunction, especially low molecular weight proteinuria, in the detection of early stages of diabetic nephropathy. PMID- 1451037 TI - Effects of clentiazem (TA-3090) and nifedipine on basal circulating catecholamine levels and on stimulation-evoked adrenal catecholamine secretion in anesthetized dogs. AB - The effects of TA-3090 (clentiazem) and nifedipine on basal sympathoadrenal activity and on the adrenal medullary response during splanchnic nerve stimulation were studied in dogs anesthetized with sodium pentobarbital. Plasma concentrations of epinephrine and norepinephrine were measured in aortic and adrenal venous blood before and after acute administration of the drugs, as well as during left splanchnic nerve stimulation before and after administration of drugs. Following intravenous injections, TA-3090 (30, 100, and 300 micrograms/kg) did not affect basal circulating catecholamine levels, whereas nifedipine (10, 30, and 100 micrograms/kg) markedly increased aortic epinephrine and norepinephrine concentrations in a dose-dependent manner in correlation with progressive decreases in mean arterial pressure. The changes in aortic epinephrine and norepinephrine concentrations were inversely related to those in mean arterial pressure (r = 0.603, p < 0.01; r = 0.536, p < 0.01; respectively). In response to direct splanchnic nerve stimulation (2 Hz, 2 ms, 1 min, 12 V), adrenal venous epinephrine and norepinephrine concentrations significantly increased, with a high degree of reproducibility. The catecholamine responses to splanchnic nerve stimulation were not affected by either TA-3090 or nifedipine at any dose tested. The present results suggest that the increases in circulating catecholamine levels following nifedipine administration are due to baroreflex activation secondary to the drug-induced hypotension. The study indicates that both TA-3090 and nifedipine did not significantly affect L-type Ca2+ channels related to catecholamine release in the adrenal medulla under the present experimental conditions. PMID- 1451039 TI - Sensitivity of early human vision to 3-D orientation in line-drawings. AB - The modern "textbook" view of visual perception contains an inherent paradox. On the one hand, it claims that relatively simple edge-extraction processes requires a stimulus exposure of approximately 50 ms. On the other hand, it says that the identification of objects in photographs and line-drawings can be highly accurate with exposure durations as short as 100 ms. It is tempting to conclude that all the difficult work of perception occurs in the 50 ms that elapse between when these two tasks are accomplished. This article argues against this view, suggesting instead that much more than edge-extraction is accomplished by the early visual processes. To illustrate this view, a computational model is described that is capable of recovering the 3-D orientation of objects from some line-drawings, rapidly and in parallel. Data from recent visual search experiments with human observers are presented in support of this model and the implications of this view for the "textbook" view are discussed. PMID- 1451038 TI - Prostaglandin production by porcine allantochorion in vitro: effect of cortisol infusion in vivo. AB - The effect of cortisol infusion into the porcine fetus on subsequent prostaglandin (PG) production in vitro by the fetal placenta (the allantochorion) was studied. Also, the possible in vitro effects of glucocorticoids and other steroids on PG production by dispersed cells were examined. Two fetuses in each of 6 sows were catheterized on day 100 or 101 of gestation (normal gestation is 114-116 days); one was infused with cortisol (6 mg/day) and one with saline for 5 days beginning on day 103. On day 108, fetal allantochorionic tissue was aseptically collected from the infused fetuses and 2 uninfused litter mates (controls). Pieces of tissues were cut from the allantochorion (4 sows) and dispersed cell preparations were made from each fetus (4 sows). Each preparation was cultured for 24 h, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha (prostacyclin metabolite) measured. In vivo cortisol infusion had no significant effect on the in vitro production of PGE2 or PGF2 alpha by tissues or dispersed cell preparations. However, tissue from the fetuses infused with cortisol produced significantly less 6-keto-PGF1 alpha than uninfused controls (54% of control, p < 0.05). The dispersed cells from uninfused fetuses and 2 cortisol-infused animals were also incubated for 24 h with 10(-7) and 10(-9) M concentrations of estrone, estradiol, progesterone, cortisol, and dexamethasone, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha was measured. No significant effect of any of these steroids in vitro on prostanoid production was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451040 TI - Recognizing novel views of three-dimensional objects. AB - The purpose of the experiments reported was to examine how novel, three dimensional shapes are represented in long-term memory and how this might be differentially affected by monocular and binocular viewing. Three experiments were conducted. The first experiment established that slide projections of the novel objects could be recognized readily if seen in the same orientation as seen during learning. The second and third experiments examined generalization to novel depth rotations of the objects. The second experiment used slide projections of the objects. The results indicated that the representation of the objects seen during training was quite viewpoint-specific as recognition of objects in novel orientations was relatively poor. In the third experiment subjects were shown the real objects under monocular or binocular viewing. Overall, the results are consistent with a growing body of recent research showing that, at least under certain conditions, the visual system stores viewpoint-specific representations of objects. PMID- 1451041 TI - Metric invariance in object recognition: a review and further evidence. AB - Phenomenologically, human shape recognition appears to be invariant with changes of orientation in depth (up to parts occlusion), position in the visual field, and size. Recent versions of template theories (e.g., Ullman, 1989; Lowe, 1987) assume that these invariances are achieved through the application of transformations such as rotation, translation, and scaling of the image so that it can be matched metrically to a stored template. Presumably, such transformations would require time for their execution. We describe recent priming experiments in which the effects of a prior brief presentation of an image on its subsequent recognition are assessed. The results of these experiments indicate that the invariance is complete: The magnitude of visual priming (as distinct from name or basic level concept priming) is not affected by a change in position, size, orientation in depth, or the particular lines and vertices present in the image, as long as representations of the same components can be activated. An implemented seven layer neural network model (Hummel & Biederman, 1992) that captures these fundamental properties of human object recognition is described. Given a line drawing of an object, the model activates a viewpoint-invariant structural description of the object, specifying its parts and their interrelations. Visual priming is interpreted as a change in the connection weights for the activation of: a) cells, termed geon feature assemblies (GFAs), that conjoin the output of units that represent invariant, independent properties of a single geon and its relations (such as its type, aspect ratio, relations to other geons), or b) a change in the connection weights by which several GFAs activate a cell representing an object. PMID- 1451042 TI - Variant points of view on viewpoint invariance. AB - In order to recognize an object, the visual system must make abstraction of proximal stimulus variations concomitant with the incidental vantage point. Theoretical models can be distinguished according to the degree to which they require the achievement of viewpoint independence prior to matching a stored object model. Recognition-by-components is one theory which incorporates the realization of general viewpoint invariance as one of its hallmarks. Some aspects of this theory, especially the orientation independence of the represented relations between object parts, are scrutinized. Next, an alternative approach is sketched in which object recognition is accomplished on the basis of a stimulus description which is dependent on the object's orientation, but which makes abstraction of other stimulus variations. Relevant neurophysiological findings are discussed, as well as behavioural evidence from experiments investigating orientation-dependent priming effects in the perception of biological motion. PMID- 1451043 TI - Perceptual use of nonaccidental properties. AB - Under the assumption of a general viewpoint, particular image properties, such as cotermination, straightness, and parallelism, can be used to infer, more or less reliably, the corresponding characteristics in the world. In this paper, the literature about these nonaccidental properties (NAPs) is reviewed to trace its historical roots, to list the properties that function as NAPs, and to discuss the psychological evidence for their detection and use. Against this background, four experiments are reviewed and four are fully described that were designed to test the perceptual use of skewed symmetry (SS), which results from orthographic projection of planar bilateral or mirror symmetry (BS). Despite the large symmetry advantage obtained in all experiments, SS is only perceived as BS-in depth in cases of closed polygons or dot patterns with higher-order types of symmetry. In all random dot patterns and in some symmetric patterns with low "Gestalt", subjects relied on more local groupings which are qualitatively affine invariant, such as clusters based on proximity or curvilinearity. Based on previous approaches in the literature and these new findings, I suggest some distinctions between different ways of using NAPs, which might foster further research. PMID- 1451044 TI - Orientation congruency effects in visual search. AB - Subjects searched for the letter E in a background of Ls and Fs in displays that had 1, 2, 4, 8, or 12 letters. The letters could be shown at one of six orientations (upright or rotated clockwise in 60 degrees increments). The displays were either congruent for orientation (all letters had the same orientation) or incongruent (letters in haphazard orientations except for the target on E-present trials). Search time increased linearly with the number of letters in the display, and more so for E-absent trials than for E-present trials. Letter orientation, in general, increased search time and produced an M shaped function. Furthermore, orientation effects were attenuated in congruent displays relative to those produced by incongruent displays. The results demonstrated systematic orientation effects on the time to search for a simple pattern embedded in simple backgrounds, and provided converging evidence for the orientation-congruency effect found by Jolicoeur (1990b, Journal of Experimental Psychology: Human Perception and Performance, 16, 351-364). PMID- 1451045 TI - Texture discrimination with and without abrupt texture gradients. AB - A common assumption is that effortless, visual texture discrimination relies on the detection of gradients between two textures. This assumption was assessed in two experiments with manipulations that smoothed (Experiment 1) or interrupted (Experiment 2) the gradient between textures comprising L- and X-type micropatterns. Compared to discrimination performance when there was an abrupt discontinuity between juxtaposed textures, performance declined moderately (about 10 percent) when the texture boundary was smoothed. In this case the two textures were asymmetrically discriminated but there was no interaction of this asymmetry with the abruptness of the texture gradient. Abrupt texture gradients, therefore, are not a necessary condition for the asymmetrical discrimination of two textures. A comparison of discrimination performance with juxtaposed textures- having an abrupt gradient--and discrimination performance when the textures were separated into distinct regions--by non-textured areas--yielded very similar results across several texture pairs. Taken together these results indicate that, in certain instances, texture discrimination may involve pattern classification like processes that are operative in the absence of texture gradients. PMID- 1451046 TI - Acute pain management: i.v. patient controlled analgesia places the patient in control. PMID- 1451047 TI - Breast cancer: recent progress. PMID- 1451048 TI - Where are you when we need you? PMID- 1451049 TI - Preoperative functional anxiety: a conceptual framework. AB - Preoperative functional anxiety is an important phenomenon for the patient undergoing surgical intervention. Functional anxiety facilitates the patient's ability to cope with surgery. Personal control enhances the patient's coping and modifies anxiety to a functional level. The phenomenon of preoperative functional anxiety and related concepts of coping and locus of control have a direct effect on the concept of postoperative recovery. Current research is focusing primarily on preoperative anxiety levels and postoperative recovery. There is a need for further nursing research to develop nursing theory about the concepts of coping and personal control as they relate to preoperative functional anxiety and postoperative recovery. This paper focuses on the development of a conceptual framework for understanding the biopsychosocial phenomenon of preoperative functional anxiety. PMID- 1451050 TI - Production of matrix metalloproteinase-2 and metalloproteinase-3 related to malignant behavior of esophageal carcinoma. A clinicopathologic study. AB - BACKGROUND: Matrix metalloproteinases (MMP) are a gene family of zinc enzymes capable of degrading almost all of the extracellular matrix macromolecules in vivo. Their enzymic activities are believed to be responsible for tumor invasion and metastasis. METHODS: In this study, using peroxidase-antiperoxidase method, monospecific antisera against MMP-1 (tissue collagenase), MMP-2 (type IV collagenase/72-kilodalton [KD] gelatinase), and MMP-3 (stromelysin) were applied to 29 squamous cell carcinomas and normal epithelium of the esophagus to identify cells synthesizing and secreting these enzymes. RESULTS: Immunoreactivity of MMP 1, -2, and -3 was observed in small cancer nests of the deeply invasive or marginal portion of the tumor. Among the 29 patients studied, the presence of at least one MMP was observed in 17 (58.6%). All three enzymes were observed in six (20.6%) patients, MMP-2 and -3 in five (17.2%) patients, only MMP-2 in three (10.3%) patients, and MMP-3 alone in three (10.3%) patients. There was a good correlation among histologic stage and tumor invasion, lymph node metastasis, and MMP expression. In particular, expression of MMP-2 and -3 was closely related to lymph node metastasis and vascular invasion. CONCLUSIONS: These results suggest that MMP, especially MMP-2 and -3, play an important role in tumor invasion and metastasis and that analysis of MMP-2 and -3 production is useful for evaluation of malignant potential in esophageal carcinoma. PMID- 1451051 TI - Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis. AB - For 15 patients with refractory gastric cancer and peritoneal metastasis, intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C combined with extensive surgery was prescribed. The antitumor effects were assessed cytohistologically in pre-IPHP and post-IPHP specimens of the abdominal effusion and peritoneal tissue. Gastric cancer cells in the abdominal effusion and/or lavage vanished from post-IPHP peritoneal exudate obtained from the pouch of Douglas. Peritoneal tissues from nine patients were harvested just after the IPHP treatment. All the nuclei of cancer cells were pyknotic in three of nine patients, and two of these three patients are alive with no local recurrence; one patient died of hepatic metastasis. In the remaining six patients, four with preoperative ascitic effusion and positive post-IPHP histologic findings died of peritoneal, intraabdominal, and pericardial metastases. The other two had some residual microscopic foci in the subperitoneal deep layer; one patient died of pleural recurrence, and the other is alive with no evidence of recurrence 42 months after the IPHP. Among the other six patients, whose post-IPHP peritoneal tissues were not available because of disappearance of disseminating foci as a result of the IPHP, two are living with no recurrence and, of the remaining four patients, three died of hepatic and intraabdominal metastases and the other one died of other causes. The histologic findings are suggestive of the following: (1) uniform heat and drug distribution in the abdominal cavity with IPHP treatment, except for an area adjacent to the inflow point of the perfusate; and (2) limited penetration of heat and drug through the subperitoneal layer. Thus, IPHP treatment results in complete destruction of cancer cells in the abdominal effusion and on and just beneath the peritoneum. PMID- 1451052 TI - Schedule-dependent inhibition of thymidylate synthase by 5-fluorouracil in gastric cancer. AB - BACKGROUND: An optimal treatment schedule of 5-fluorouracil (5-FU) remains to be clarified. METHODS: A randomized study was conducted to investigate schedule dependent thymidylate synthase (TS) inhibition by 5-FU in 16 patients with gastric cancer who underwent surgical resection. Surgical specimens of tumor, normal gastric mucosa, and regional lymph nodes were obtained 12 hours after administration of 5-FU either as a continuous infusion (1000 mg/m2 for 48 hours) or as a bolus injection (500 mg/m2 x 2 in 48 hours). RESULTS: The total TS activity (567.8 +/- 294 fmol/mg protein) and the rate of TS inhibition (74.7 +/- 23.1%) in cancer tissues were significantly higher in the continuous-infusion group than in the bolus-injection group (228.5 +/- 104.6 fmol/mg protein and 48.8 +/- 12%, respectively). Likewise, the total TS activity (807.4 +/- 440.3 fmol/mg protein) and the rates of TS inhibition in lymph nodes (72.3 +/- 17.1%) and in normal gastric mucosa (85.1 +/- 12.2%) were significantly higher in the continuous-infusion group than those in the bolus-injection group (232.4 +/- 142.3 fmol/mg protein and 53.6 +/- 17.0% in lymph nodes and 46.5 +/- 14.3% in normal gastric mucosa, respectively). There was a significant correlation between the total TS activity and TS inhibition. CONCLUSIONS: Continuous infusion of 5-FU provides a superior antimetabolic effect in the treatment of gastric cancer, which may lead to a superior antitumor effect. PMID- 1451053 TI - Adenocarcinoma of the proximal small intestine. A marker for familial and multicentric cancer? AB - BACKGROUND: Adenocarcinoma of the small intestine is uncommon. The Hawaii Tumor Registry (HTR) has identified 49 of these tumors since 1960, and the Japan-Hawaii Cancer Study (JHCS) has identified only four of these tumors among a cohort of 8006 Hawaiian-Japanese men followed up for a period of 22 years. Each of the four men reported by the JHCS had multicentric gastrointestinal cancers. METHODS: Newly diagnosed cancers are recorded separately by the HTR and JHCS, and linkage is maintained between the two files. Family histories are available from the JHCS, and these are supplemented by a state population file maintained by the Department of Genetics, University of Hawaii. RESULTS: Five men, all Japanese, were found to have carcinoma of the proximal small intestine. Each had multicentric carcinomas of the gastrointestinal tract. Carcinoma of the stomach and colon was found in the primary relatives of each of four men whose families lived in Hawaii. CONCLUSIONS: The familial clustering of uncommon neoplasms (small bowel carcinoma and multicentric large bowel carcinoma), and the concurrence of gastric and colonic carcinoma suggests that these subjects have a genetic trait that increases susceptibility to a broad range of carcinogens. PMID- 1451054 TI - Expression of p53 protein in invasive colorectal carcinomas of different histologic types. AB - BACKGROUND: This study was performed to determine whether morphologic differences of colonic cancer types can be related to different genotypes of these tumors. METHODS: Paraffin sections of 76 human invasive colorectal carcinomas were examined for the overexpression of p53 oncoprotein with the avidin-biotin complex peroxidase staining procedure and CM-1 antiserum, which detects p53 protein in paraffin-embedded material. The tumors were categorized as mucinous (22 cases), most of which originated from adenomas, and nonmucinous, which were subdivided into carcinomas originating from adenoma-carcinoma sequence (ACS) (29 cases) and de novo (DN) carcinomas (25 cases). RESULTS: Nineteen DN carcinomas (76%), 21 ACS carcinomas (72%), and 8 mucinous carcinomas (36%) exhibited detectable amounts of p53 protein in the tumor cell nuclei. Strong overexpression of p53 protein coincided with a high percentage (> 40%) of stained nuclei in 40% of ACS and 48% of DN carcinomas versus 9% of mucinous tumors. The percentage of stained nuclei, intensity of staining, and distribution of the stained areas did not correlate with the grade of differentiation or the invasive edge of the tumors. Along with nuclear staining of the tumor area, a distinct perinuclear staining of normal epithelial cells adjacent to the tumor was observed in 48% of DN, 7% of ACS, and 9% of mucinous carcinomas. CONCLUSIONS: The current results, in combination with the recently published data on Ki-ras and c-myc alterations, indicate that mucinous carcinomas differ from nonmucinous colorectal carcinomas in their genetic lesions. PMID- 1451055 TI - Expression of p53 protein in colorectal cancer and its relationship to short-term prognosis. AB - BACKGROUND AND METHODS: The expression of p53 protein in 100 large bowel cancers was studied immunohistochemically by use of a monoclonal antibody (PAb1801). RESULTS: Immunoreactivity was found in 61.0% of specimens from 100 patients with colorectal cancer. The pattern of p53 expression was mainly detected in the nuclei of the cancer cells. There was no significant correlation between the expression of p53 and the histologic grade, tumor size, serosal invasion, lymphatic invasion, venous invasion, lymph node metastasis, or liver metastasis. However, patients with p53-positive tumors had a greater relative risk of death compared with those with p53-negative tumors. The p53 negative-tumors showed a recurrence rate of 5.9%; for the p53 positive-tumors, a recurrence rate of 23.8% was recorded. The 3-year survival rate was 96.7% of 39 patients with p53-negative carcinomas and 61.8% for the patients with p53-positive tumors; there was a significant difference in the rate between the two groups of patients (P < 0.05). The growth fraction of p53-positive tumors determined with a monoclonal antibody against DNA polymerase alpha (49.0%) was significantly higher than that of p53 negative tumors (40.7%, P < 0.01). CONCLUSIONS: These results suggest that the immunoreactivity of p53 may be a biologic marker of prognostic significance. PMID- 1451056 TI - Effects of hyperthermia and iodine-131-labeled anticarcinoembryonic antigen monoclonal antibody on human tumor xenografts in nude mice. AB - BACKGROUND: Many studies have demonstrated synergistic interaction between hyperthermia and radiation. This study was undertaken to determine whether hyperthermia could enhance the effect of radioimmunotherapy (RIT) in the treatment of human colon adenocarcinoma xenografts in nude mice. METHODS: The experiments were conducted in two parts. During the first part of the study, preliminary information was obtained regarding the effect of various temperatures (41 degrees C, 42 degrees C, and 43 degrees C for 45 minutes) and iodine-131 labeled anticarcinoembryonic antigen (CEA) monoclonal antibodies (RMoAb) with administered activity ranging from 130 +/- 19 microCi to 546 +/- 19 microCi on tumor regrowth delay (TRD) and volume doubling time. This information was used in Part 2 of the study, which included four groups of mice: (1) a control group, (2) a group treated with hyperthermia, (3) a group treated with RMoAb, and (4) a group treated with a combination of RMoAb and hyperthermia. RESULTS: Maximum and significantly increased TRD was observed in the group treated with RMoAb and hyperthermia (slope, 0.057) compared with the control group (slope, 0.322), the hyperthermia-treated group (slope, 0.302), and the group treated with RMoAb alone (slope, 0.098). The ratio of the slopes between the groups treated with RMoAb and those treated with RMoAb and hyperthermia was 1.72. No correlation was detected between the percent of antibody uptake in the tumor and tumor regression in the groups treated with heat and RMoAb and those treated with RMoAb alone. CONCLUSIONS: The results of these experiments show that hyperthermia increased the effectiveness of iodine-131-labeled anti-CEA monoclonal antibodies against human colon carcinoma xenografts in nude mice. This study offers a rationale for combining hyperthermia and low-dose radiation produced from RIT in clinical practice. PMID- 1451057 TI - Prognostic factor of telecobalt therapy for early glottic carcinoma. AB - BACKGROUND: Local control rates of T1 and T2 glottic carcinoma treated with radiation alone were reported as 80-91% and 63-76%, respectively. The authors investigated the factors that affect the local control rate for early glottic carcinoma. METHODS: From 1967 through 1982, 330 patients with early glottic carcinoma (T1: 274 patients; T2: 56) were treated with telecobalt therapy at the Department of Radiology, Osaka University Hospital, Osaka, Japan. RESULTS: Five year actuarial survival rates of patients with T1 and T2 were 79% and 80%, respectively. Five-year local disease control rates of patients with T1 and T2 disease were 81% and 67%, respectively. In 243 of 254 patients treated with 2 Gy a day, tumor response could be evaluated at the dose level of 40 Gy. For tumors treated with a daily dose of 2 Gy, local control rates of 153 tumors that disappeared at 40 Gy and 90 tumors that persisted at 40 Gy were 83% and 62%, respectively (P < 0.001). Field size and daily fraction size did not affect the local control rate. CONCLUSION: Evaluation of tumor response at 40 Gy was an important indicator of local disease control for early glottic cancers treated with 2 Gy a day. PMID- 1451058 TI - Malignant transformation in Paget disease of bone. AB - BACKGROUND: The previously reported incidence of malignant transformation of Paget disease up to 5.5% and its dismal prognosis have prompted the clinical investigation of a large population with Paget disease. METHODS: A chart review of symptomatic and asymptomatic patients with a diagnosis of Paget disease between 1970 and 1985 at four large Montreal Hospitals revealed 1078 patients. Eight patients with malignant transformation were studied in detail. RESULTS: The incidence of malignant transformation was 0.7%, and the most frequent histologic type was osteogenic sarcoma. The most prevalent site was the femur, and pathologic fracture with focal osteolysis was present in 50% of patients at the initial appearance of the tumor. Healing at the fracture site was demonstrated in one patient. Another patient died of uncontrollable hemorrhage. A case of malignant lymphoma in Paget disease is recorded. CONCLUSIONS: Surgery or biopsy should be preceded by preoperative scintigraphic bone blood flow evaluation and, if necessary, administration of a preoperative course of mithramycin and selective embolization to minimize bleeding. The prognosis of malignant transformation in Paget disease is poor, although one patient with malignant lymphoma survived after aggressive treatment. Early biopsy and aggressive treatment should not be delayed. PMID- 1451059 TI - The prognostic value of cytogenetic analyses in patients with acute nonlymphocytic leukemia treated with the same intensive chemotherapy. AB - BACKGROUND: Some specific chromosome abnormalities for the leukemias have been proven to be associated with the prognosis of acute nonlymphocytic leukemia (ANLL). However, most of these reports included patients treated with different protocols. Therefore, some bias has been involved in the evaluation of the prognostic factors in such reports. METHODS: The authors studied the morphologic, cytogenetic, and clinical features of 136 patients (86 males and 50 females) with de novo ANLL treated with the same protocol of intensive induction chemotherapy using multivariate analyses. RESULTS: Chromosome abnormalities were detected in 62.5% of the patients. The overall complete remission (CR) rate of disease was 85.5% in these patients. More than 90% of the patients with t(8;21) and pseudodiploid abnormalities achieved experienced CR. However, CR rates in the patients with abnormalities of chromosome 5 or 7 were 50%. With multivariate analyses by the type of karyotypic abnormality, CR duration and survival time of the patients with t(8;21) were longer than those of patients with normal karyotype and abnormalities of chromosome 5 or 7. Abnormalities of chromosome 5 or 7 and hyperdiploid were associated with poor prognosis. Older age and lower platelet counts also were factors contributing to shorter survival times. With the analysis with French-American-British (FAB) classification, only hypoplastic leukemia was a poor prognostic factor. CONCLUSIONS: These data suggest that cytogenetic analyses plays an important role in estimating the prognosis of patients treated with intensive induction chemotherapy. PMID- 1451060 TI - Prognostic significance of histologic parameters of soft tissue sarcomas. AB - BACKGROUND AND METHODS: A univariate and multivariate analysis for the correlation between histomorphologic factors and prognosis was made using data from 1116 patients with soft tissue sarcoma, including 1005 cases available with complete histologic and follow-up data. RESULTS: The overall 5-year survival rate was 43.6%. The univariate analysis using Kaplan-Meier survival curves showed that tumor differentiation, cellularity, nuclear atypia, cellular pleomorphism, mitotic activity, amount of fibrous stroma, extent of myxoid areas, extent of tumor necrosis, and histologic grading (determined by the estimated range of malignancy for each type of sarcoma using a reported guideline) were all significant prognostic factors in the overall soft tissue sarcoma group. By a multivariate analysis using a procedure based on the Weibull model to failure data, the histologic grading and extent of tumor necrosis were proved to be prognostically significant in the overall sarcoma group. However, after additional analysis on each histologic type of sarcoma, it was determined that both tumor necrosis and histologic grading were applicable in only two types: malignant fibrous histiocytoma and leiomyosarcoma. Liposarcoma, synovial sarcoma, and malignant schwannoma each also showed some determinable factor of prognostic significance. CONCLUSIONS: It was concluded that there seemed to be no single universal prognostic parameter that could be applied to each soft tissue sarcoma type. These results suggest that the predictive significance of the various histologic parameters should be based on each specific type of sarcoma. PMID- 1451061 TI - DNA flow cytometry of epithelioid sarcoma. AB - DNA ploidy of paraffin-embedded tissue from 11 patients with epithelioid sarcoma and 20 control specimens (granuloma annulare and sarcoid) was studied. DNA aneuploidy was found in 64% of the epithelioid sarcomas and in none of the control samples. Aneuploidy did not correlate with necrosis, vascular invasion, or mitotic rate. There was also no association of aneuploidy with adverse outcome. PMID- 1451062 TI - Extraskeletal myxoid chondrosarcoma. A clinicopathologic study of ten patients with long-term follow-up. AB - Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma that has been reported to have a relatively good prognosis. The authors report ten patients with EMC on whom there was a minimum follow-up of 10 years. The patients' ages ranged from 31 to 72 years (mean, 57 years); there were six men and four women (seven white, three black). The tumor locations included the knee area and thigh (three patients each), the shoulder (two patients), and the leg and foot (one patient each). The tumors ranged from 3.5 to 18 cm in greatest dimension (median, 11.5 cm). All cases had typical histologic features. Lung metastases developed in all patients but one, and three patients had extrathoracic metastases (one in regional lymph nodes; one in subcutis; and one widespread). Four of the patients who had metastases also had local recurrence, as did the only patient without known metastases. Seven patients died of tumor at 4, 5, 8, 10, 15, 16, and 17 years, respectively, and the three remaining patients were alive with metastatic disease at latest follow-up of 13, 14, and 16 years. The authors' results are distinctly different from those previously reported in series with shorter follow-up times. The authors conclude that extraskeletal myxoid chondrosarcomas are indolent but resilient and capricious tumors with a high potential for metastasis, especially to the lungs, over the long-term. PMID- 1451063 TI - CA 15-3 in patients with locoregional and metastatic breast carcinoma. AB - BACKGROUND: The value of circulating CA 15-3 levels was assessed in 129 patients with recurrent breast carcinoma. METHODS: Patients were divided into four subgroups, according to the following: Group A, locoregional recurrence alone; Group B, locoregional and subsequent systemic recurrence; Group C, combined locoregional and systemic recurrence; and Group D, differing sites of systemic disease. RESULTS: One of 14 patients with locoregional disease alone had increased levels of CA 15-3 (> 25 U/ml). However, 96% of patients (22 of 23 patients) with combined local and systemic disease had increased tumor marker levels. The difference in CA 15-3 levels in patients with combined disease compared with patients with local disease alone was statistically significant (117.0 versus 17.5 U/ml, respectively; P < 0.02). Twenty-four patients with locoregional recurrence later had distant metastasis develop. In this group, patients with an increased CA 15-3 value had a significantly shorter lead time to the development of distant metastases compared with patients with normal tumor marker levels (20.8 +/- 3.3 versus 10.3 +/- 2.7 months, respectively; P < 0.03). CA 15-3 values at diagnosis were increased in 88% of 115 patients with metastatic disease. There was no significant difference in CA 15-3 levels among metastases to lung, liver, and bone nor was there any difference between single and multiple sites of distant metastasis. CA 15-3 is an excellent marker for systemic recurrence of breast carcinoma. CONCLUSIONS: Increased levels and no clinical evidence of recurrence strongly indicate the presence of occult metastatic disease. PMID- 1451064 TI - Pelvic exenteration for the treatment of vulvar cancer. AB - BACKGROUND: Advanced vulvar cancer can be treated by pelvic exenteration. METHODS: A clinical review of patients treated by exenteration surgery for vulvar cancer was performed. RESULTS: From 1950 through 1989, 19 patients underwent pelvic exenteration for advanced or recurrent squamous cell cancer of the vulva. The mean age was 53 years (median, 50 years; range, 40-74 years). The cumulative 5-year survival was 60%. Fourteen patients had posterior exenteration; 2 had anterior exenteration; and 3 had total exenteration. The survival was significantly influenced by lymph node status. When lymph nodes were not involved, 10 of 14 patients survived, whereas all 5 patients with lymph node involvement died of disease (P = 0.002). When exenteration was performed as primary therapy, 7 of 11 patients survived, whereas 3 of 8 survived when exenteration was performed for recurrent disease (P = 0.4). The extent of vulvar involvement did not influence survival (P = 0.99). There was no mortality, but ten patients had complications, including vesicovaginal fistula (three); stomal hernia (two); abscess (one); stress urinary incontinence (one); deep venous thrombosis (one); conduit leak (one); enterocutaneous fistula (one); and small intestinal obstruction (one). CONCLUSIONS: Acceptable survival for advanced or recurrent vulvar cancer can be achieved with pelvic exenteration, but the presence of metastatic disease to lymph nodes markedly decreases survival. PMID- 1451065 TI - Roles of Langerhans' cells and T-lymphocytes infiltrating cancer tissues in patients treated by radiation therapy for cervical cancer. AB - Correlations between infiltration of immunologic cells in tumor tissues and prognosis of radiation therapy were investigated for 275 patients with cervical cancer who were treated with radiation therapy alone, including 216 patients with Stage III squamous cell carcinomas and 59 with adenocarcinomas of all stages. Langerhans' cell (LC) and T-cell were stained immunohistochemically on the specimens excised from the cervical cancer. In squamous cell carcinoma, 5-year survival rates for patients with LC infiltration were significantly better than those without LC (78% versus 60%; P < 0.01). The 5-year survival rate of patients with T-cell infiltration also was significantly better than that of patients without such infiltration (83% versus 61%; P < 0.05). Similar trends were observed in patients with adenocarcinoma; 5-year survival rates for patients with LC infiltration and those without LC infiltration were 49% and 25%, respectively (P < 0.025). The survival rates for patients with T-cell infiltration and those without were 50% and 33%, respectively (P < 0.1). An analysis of patterns of failure of radiation therapy demonstrated that the favorable prognosis in LC infiltration was attributable mainly to improvement of local control rates, but that in T-cell infiltration was not. T-cells infiltrated into tumor specifically in the patients with LC infiltration in both cell types. The authors suggest that the host anti-cancer immune response of individual patients may be remarkably different at the first step of antigen recognition by LC. The LC may induce T cell-mediated antitumor response and improve local response in radiation therapy. PMID- 1451066 TI - The development of hypercalcemia in a patient with an ovarian tumor producing parathyroid hormone-related protein. AB - Hypercalcemia developed in a 34-year-old woman with a clear cell carcinoma of the ovary. Osseous involvement with the tumor cells was not present. Primary hyperparathyroidism was absent. Operative partial resection of the metastatic supraclavicular lymph node, followed by radiation therapy, decreased her serum calcium concentrations. This case belongs to the category of humoral hypercalcemia of malignancy (HHM). Detection of a significant quantity of immunoreactive parathyroid hormone-related protein (PTH-rP) in the metastatic lymph node suggested that the HHM of the patient was induced by PTH-rP produced by the tumor. From a review of 17 cases of ovarian tumors showing HHM-like morbidity, it was found that clear cell carcinoma and cystadenocarcinoma were the major types of ovarian tumors associated with HHM. PMID- 1451067 TI - Different antigenic nature in apparently healthy women with high serum CA 125 levels compared with typical patients with ovarian cancer. AB - BACKGROUND: CA 125 is a representative ovarian cancer-associated antigen defined by monoclonal antibody OC125. Recently, monoclonal antibodies were produced (designated 130-22 and 145-9) that were reactive with CA 125 but bound to a separate epitope named CA 130. There was a close correlation between serum CA 125 and CA 130 values in most instances. However, among more than 8000 serum samples, 5 apparently normal women had high serum CA 125 values, despite having normal CA 130 values. In this study, the antigenic nature of these five women was investigated. METHODS: Using gel chromatography, the molecular masses of CA 125 and CA 130 were estimated that were found in the five women with false-positive CA 125 values. The sera were examined using double-determinant assays combining iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OCI25-coated or 145-9 coated beads. RESULTS: The molecular masses of both CA 125 and CA 130 were estimated as greater than 1000 kilodaltons (KD); the CA 130 mass from one of the five women with an abnormal CA 125 level was approximately 200 KD using gel chromatography. Using the double-determinant assays that combined iodine-125 labeled OC125 or iodine-125-labeled 130-22 with OC125-coated or 145-9-coated beads, high radioactivity was found only in the homologous assay using iodine-125 labeled OC125 with OC125-coated beads. These results suggest that the antigenic nature of CA 125 found in apparently healthy women differs from that found in patients with ovarian cancer and that CA 130 epitopes are not present. CONCLUSIONS: Measurement of serum CA 130 concentrations may be useful for excluding women with falsely elevated CA 125 values. PMID- 1451068 TI - Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. AB - BACKGROUND: Prostate cancer is the most prevalent nonskin cancer among men in the United States and is the second leading cause of cancer deaths in men. The cause of prostate cancer remains obscure. Recently it was hypothesized that low levels of vitamin D, a hormone with potent antitumor properties, may increase the risk for clinical prostate cancer. METHODS: Because the major source of vitamin D is casual exposure to ultraviolet (UV) radiation, the authors examined the geographic distributions of UV radiation and prostate cancer mortality in 3073 counties of the contiguous United States using linear regression and trend surface analyses. RESULTS: The geographic distributions of UV radiation and prostate cancer mortality are correlated inversely (P < 0.0001). Prostate cancer mortality exhibits a significant north-south trend, with lower rates in the South. These geographic patterns are not readily explicable by other known risk factors for prostate cancer. CONCLUSIONS: These data lend support to the hypothesis that UV radiation may protect against clinical prostate cancer. Viewed in conjunction with other recent data, including those demonstrating a differentiating effect of vitamin D on human prostate cancer cells, these findings suggest that vitamin D may have an important role in the natural history of prostate cancer. PMID- 1451069 TI - Prognostic factors for survival of patients with bidimensionally measurable metastatic hormone-refractory prostatic cancer treated with single-agent chemotherapy. AB - BACKGROUND: A range of response proportions have been reported using the same single-agent inpatients with hormone refractory prostatic cancer. To assess whether these results were due to imbalances in prognostic factors, the authors evaluated a series of prognostic factors for survival in patients with prostatic cancer treated with chemotherapy. METHODS: Complete data sets were available in 146 patients, in whom 27 individual variables were considered in univariate analysis. Significant factors (P < 0.05) were then evaluated using regression analysis along with transformations of the data to obtain a Cox and exponential model. The derived model was then evaluated on an independent data set from the National Cancer Institute treated with suramin. RESULTS: In univariate analysis in order of significance, the serum alkaline phosphate (0.0018), serum lactic dehydrogenase (0.006), prior radiation therapy (0.007), serum aspartate amino transferase (0.02), presence of liver disease (0.033), and pretreatment Karnofsky performance status (0.04) were associated with survival. In the regression analysis, only the log-transformed lactic dehydrogenase (LDH) and normal versus abnormal alkaline phosphatase were significant. This model was confirmed with an independent data set from patients treated with the putative growth factor inhibitor suramin. CONCLUSIONS: This analysis emphasizes important factors that can be used to stratify patients in future phase II and III trials. PMID- 1451070 TI - Concurrent vinblastine and radiation therapy in bladder cancer. AB - BACKGROUND: Since mid-1987, 29 patients with invasive transitional cell carcinoma of the urinary bladder (T1-3 N0-X M0) were treated with concurrent radiation therapy (RT) (target dose [TD], 62-66 Gy) 1.8-2.0 Gy/day for 5 days a week with a break in the middle of treatment of 2-3 weeks and vinblastine weekly 2 mg/5-12 h intravenous infusion. METHODS: Patients were divided into two groups: those had only the initial therapy (Group 1) and those who had both courses of RT combined with vinblastine (Group 2). Patients eligible for cystectomy were selected for full-dose RT, according to the results of treatment with a TD of 36 Gy. RESULTS: Tolerable toxicity rates were noted. No patient was excluded from the study. The authors report a clinical complete remission rate of 71% at early evaluation of treatment and a 3-year local progression-free survival of 66% (for Group 2 patients). These results are comparable to those obtained with more aggressive chemoradiation therapy regimens. The authors also noted improved local disease control in patients who received combination therapy in comparison with the 17 patients treated with RT alone. CONCLUSIONS: The authors suggest that concurrent RT and vinblastine therapy is an attractive alternative to other chemoradiation therapy regimens, and is especially superior to RT therapy alone in caring for old patients or patients in poor general condition. PMID- 1451071 TI - Occupation and risk of uveal melanoma. An exploratory study. AB - BACKGROUND: Little is known about the cause of uveal melanoma, the most common primary intraocular malignant lesion in adults. This population-based case control study evaluated occupational exposures. METHODS: One hundred ninety-seven newly diagnosed cases of uveal melanoma participated. Approximately two control subjects matched for age, sex, and telephone exchange area were selected for each case by random-digit dialing. Data were collected by a structured telephone interview. Two systems of occupational coding were used: an occupation-exposure linkage system and the Bureau of Census data. Conditional logistic regression for matched studies was used to examine various occupational exposures while controlling for previously reported potential confounders and for family income. The occupation-exposure matrix was used to define clusters of cases exposed to a particular chemical group from various occupations. RESULTS: Odds ratios were elevated for agriculture and farming work for both industry and occupation; this was consistent across both classification systems. Elevated odds ratios also were found for occupations involving machine operations, fabrication, assembling, equipment cleaning, and exposure to metal industries. Exposure to alkylating agents and phenols was associated with a lower risk compared with all other exposures. Several self-reported exposures also were studied. Exposures associated with elevated odds ratios were inks, insecticides, gases, radioactive substances, polybromated biphenyls, and chemical solvents. CONCLUSIONS: This exploratory study suggests various occupational associations for uveal melanoma and areas for future research. PMID- 1451072 TI - A reassessment of histologic classification and an immunohistochemical study of 88 retinoblastomas. A special reference to the advent of bipolar-like cells. AB - BACKGROUND: Despite perpetual efforts of investigators, the histogenesis of retinoblastoma is still in dispute and histologic classification satisfactorily predictive of prognosis does not seem to be in use. METHODS: The authors studied 88 cases of retinoblastoma clinicopathologically and immunohistochemically, paying special attention to the presence of a "bipolar-like cell" element that would be used as one of the criteria for the diagnosis of differentiated retinoblastoma. RESULTS: Twelve cases of retinoblastoma with the bipolar-like cell element in the absence of rosettes and 41 cases of the tumor with rosettes were classified as differentiated retinoblastomas. The other 35 cases without rosettes or bipolar-like cells were classified as undifferentiated tumors. Tumor cells forming rosettes usually had positive results for synaptophysin and neuron specific enolase (NSE) and negative results for glial fibrillary acidic protein (GFAP) and S-100 protein; however, undifferentiated cells had negative results for these four antibodies. The bipolar-like cells had positive results for synaptophysin and NSE but negative results for GFAP and S-100 protein. Twelve tumors with bipolar-like cells that lacked rosettes showed no optic nerve invasion, and the patients had a significantly better prognosis (100% 5-year survival rate) than 35 patients with undifferentiated tumors (71% 5-year survival rate) (P < 0.01). CONCLUSIONS: The findings support a neuronal origin of the tumor and indicate that, not only the rosettes symbolizing the photoreceptor differentiation, but also other neuronal elements, such as bipolar-like cells, can be used as criteria for histologic classification of retinoblastoma. PMID- 1451073 TI - A randomized trial of accelerated hyperfractionated radiation therapy and bis chloroethyl nitrosourea for malignant glioma. A preliminary report of Radiation Therapy Oncology Group 83-02. AB - BACKGROUND: The third and final randomization of Radiation Therapy Oncology Group (RTOG) 83-02 was performed to identify the maximal tolerated dose and potential efficacy of accelerated hyperfractionated radiation therapy (AHRT) in 1.6 Gy twice-daily fractions for adult malignant glioma. METHODS: From December 1987 to July 1989, 304 patients with malignant glioma were stratified by age, performance status, and histologic findings and randomized to receive total AHRT doses of 48.0 or 54.4 Gy, with 80 mg/m2 of bis-chloroethyl nitrosourea (BCNU) for 3 days every 8 weeks. Distribution of other prognostic factors, including neurologic function, extent of surgery, tumor size, and sex, was comparable in each treatment arm. RESULTS: One Grade 5 radiation therapy (RT)-related toxic effect was reported (in the 54.4-Gy treatment arm), and the incidence of late Grade 3-5 RT-related toxic effects at 18 months was 1% at 48.0 Gy and 4% at 54.4 Gy. The median survival times (MST) for the 48.0 Gy and 54.4 Gy treatment arms were 11.7 and 10.8 months, respectively, comparable to the MST in prior RTOG trials with a similar proportion of patients with glioblastoma multiforme (79%). For the 123 patients who were 60 years of age or older, the MST for the 48.0 Gy and 54.4 Gy treatment arms were 8.9 and 10.4 months, respectively, and compare favorably with the MST of 6.0 months reported with standard RT and BCNU treatment used for 101 patients who were 60 years of age or older in two prior RTOG malignant glioma trials (74-01 and 79-18). Although these results differ significantly (P = 0.0015), this contrast is not significant when adjusted by performance status. CONCLUSIONS: The maximum tolerated dose of AHRT has yet to be identified, and pursuit of this information may most benefit patients with malignant glioma who are 60 years of age or older. PMID- 1451074 TI - Protein kinase C activity in human thyroid carcinoma and adenoma. AB - Protein kinase C (PKC) activity was examined in the cytosolic and particulate fractions of homogenates obtained from 12 papillary thyroid carcinomas, 12 follicular thyroid adenomas, and the adjacent normal thyroid tissue. Particulate PKC activity was elevated significantly in thyroid carcinomas compared with normal thyroid tissue (P < 0.01) and adenomas (P < 0.05). By contrast, cytosolic PKC activity of carcinomas and adenomas was lower significantly than that of normal thyroid tissue (P < 0.01). The percentage of particulate PKC activity in carcinoma and adenoma was higher than in normal thyroid tissue (carcinoma, P < 0.001; adenoma, P < 0.01). The average particulate PKC activity of carcinomas more than 3 cm in diameter was significantly lower than that of carcinomas less than or equal to 3 cm in diameter (P < 0.05). The average cytosolic PKC activity of carcinomas more than 3 cm also was lower significantly than that of smaller carcinomas (P < 0.05). These results suggest that alterations in PKC activity may be important in the development of papillary thyroid cancer. PMID- 1451075 TI - Peculiar nuclear clearing composed of microfilaments in papillary carcinoma of the thyroid. AB - BACKGROUND: Papillary carcinoma of the thyroid frequently occurs in young women. Four cases of papillary carcinoma were found in women in their 20s, and the disease was characterized by unusual morphologic and clinical features. METHODS: Four cases were analyzed clinically, grossly, microscopically, ultrastructurally, and immunohistochemically and compared with control cases of papillary carcinoma. RESULTS: The tumors histologically showed various appearances with trabecular, solid cribriform, follicular, and papillary patterns. A striking finding was that stratified cancer cell nests with prominent nuclear clearings were scattered in the tumors. Ultrastructurally, the nuclear clearings were composed of fine thread like fibrils, and they were bound unselectively to various antibodies against hormones and intermediate filaments. The four patients also had common clinicopathologic features as follows: they were all women in their 20s and their preoperative serum thyroglobulin levels were all normal despite the large size of their thyroid tumors. The tumors were grossly well encapsulated, and there was no lymph node metastasis, except in one patient who had only one positive node. CONCLUSIONS: The peculiar nuclear features were distinct from intranuclear cytoplasmic inclusions or ground-glass nuclei, and these have not been reported previously to the authors' knowledge in conventional thyroid neoplasms. These tumors might represent another subtype of papillary thyroid carcinoma. PMID- 1451076 TI - High-dose intravenous zidovudine with 5-fluorouracil and leucovorin. A phase I trial. AB - BACKGROUND: The inhibition of pyrimidine metabolism by 5-fluorouracil (5-FU) enhances the anti-cancer effects of zidovudine (formerly called AZT) in in vitro and in vivo model systems without additive toxicity. Zidovudine-induced DNA damage correlates with cytotoxicity. METHODS: A Phase I trial of high-dose continuous-infusion intravenous zidovudine therapy in combination with 5-FU and leucovorin therapy was performed. Eighteen patients with advanced malignant tumors were treated with 43 courses of oral leucovorin (50 mg every 4 hours); continuous-infusion 5-FU (800 mg/M2/day) for 72 hours (3 days); and zidovudine, begun 24 hours after the start of 5-FU and leucovorin, for 48 hours, and terminating with the end of the 5-FU infusion. Zidovudine plasma levels and zidovudine-induced DNA damage were assessed. RESULTS: Zidovudine administered in doses of 2-20 g/M2/day, added no obvious toxicity to the basic chemotherapeutic treatment with 5-FU and leucovorin but resulted in a dose-dependent biologic effect manifested by an increase in DNA strand breaks in peripheral blood cells. At doses greater than 15 g/M2/day, altered plasma kinetics of zidovudine were observed; plasma zidovudine levels increased dramatically in relation to the dose of zidovudine. Limitations in drug administration restricted administration of higher intravenous doses without achieving a maximally tolerated dose. No responses were seen in this heavily pretreated population. CONCLUSIONS: Based on the results of preclinical studies, plasma zidovudine levels greater than those achieved at the maximal dose (133 microns) are required for increased anti-cancer activity with 5-FU. Additional studies using a bolus or rapid infusion as a method of achieving higher peak levels are indicated. PMID- 1451077 TI - Education and cancer risk. AB - BACKGROUND: Socioeconomic factors have been associated, to a variable degree, with the risk of serious cancers. METHODS: The relationship between education and cancer risk was analyzed using data from a series of case-control studies conducted in northern Italy between 1983 and 1990, including 119 histologically confirmed cancers of the oral cavity and pharynx, 294 of the esophagus, 564 of the stomach, 673 of the colon, 406 of the rectum, 258 of the liver, 41 of the gallbladder, 303 of the pancreas, 149 of the larynx, 2860 of the breast, 692 of the cervix, 567 of the corpus uteri, 742 of the ovary, 107 of the prostate, 365 of the bladder, 147 of the kidney, and 120 of the thyroid, 72 Hodgkin diseases, 173 non-Hodgkin lymphomas, 117 myelomas, and a total of 6147 control subjects admitted to the same network of hospitals for acute, non-neoplastic conditions. RESULTS: Nine types of cancer were inversely related to education. Those were oral cavity and pharynx, with a relative risk (RR) of 0.3 for the highest versus the lowest level; esophagus, RR = 0.6; stomach, RR = 0.5; liver, RR = 0.7; gallbladder, RR = 0.5; larynx, RR = 0.3; cervix, RR = 0.7; endometrium, RR = 0.5; and non-Hodgkin lymphomas, RR = 0.6. Five cancer sites were directly related to education: colon, RR = 1.3; pancreas, RR = 1.3; breast, RR = 1.5; kidney, RR = 1.3; and thyroid, RR = 1.5. No consistent gradient in risk with education was observed for the six other neoplasms considered, including rectum, prostate, bladder, Hodgkin disease, and multiple myeloma. The patterns of risk for education were consistent in men and women for most cancer sites except colon, for which the direct relationship was stronger in males. CONCLUSIONS: This study confirms the existence of and quantifies a number of strong socioeconomic correlates of cancer risk and indicates a few points open to additional investigation, such as the different pattern of risk for rectal and colon cancer, the strong negative gradient for endometrial cancer, and the absence of any clear association with education for cancers of the ovary, prostate, urinary tract, lymphomas, and myeloma. PMID- 1451078 TI - The spectrum of cancer in Papua New Guinea. An analysis based on the Cancer Registry 1979-1988. AB - Malignant tumors registered with the Tumour Registry of Papua New Guinea (PNG) from 1958-1988 were analyzed with emphasis on the variation of incidence with time and different regions. Cancer incidence was generally low in PNG. During this period, carcinoma of oral cavity, cervix, breast, and skin, hepatoma, and lymphoma were the most common types of malignant lesions detected. The incidence of carcinoma of the oral cavity has increased. Currently, it is more common in the Highlands region and is associated with the spread of betel nut chewing. A threefold increase in cervical carcinoma registration was observed nationally, with a sixfold increase in the Highlands region; this was attributed both to social changes and improved registration. The incidence of breast cancer has doubled, in keeping with better registration, but there is little interregional variation. The decline in registrations of hepatocellular carcinoma is artifactual. PNG is a high-incidence area for Burkitt lymphoma, but Hodgkin disease is rare. Both Burkitt and other non-Hodgkin lymphomas are uncommon in the Highlands. A decline in the incidence of squamous carcinoma of skin was observed that was associated with improved control of tropical ulcers. The incidence of stomach cancer is falling. The registered cancer incidence in PNG is low, even when compared with that in native people from other Pacific nations, such as Fijians and New Caledonian Melanesians. Preventive measures have been hitherto ineffective, with the exception of squamous carcinoma of skin. PMID- 1451079 TI - Epidemiology of lymphomatoid papulosis. AB - BACKGROUND: Lymphomatoid papulosis is a rare skin disease with malignant potential. Its epidemiology is largely unknown. METHODS: A case-control study of lymphomatoid papulosis was done to characterize the patient population and investigate the risk factors for its development. Fifty-seven patients with biopsy-proven lymphomatoid papulosis and 67 individually matched control subjects who were recruited among relatives and acquaintances of the patients answered a standard questionnaire over the telephone. RESULTS: Among patients with lymphomatoid papulosis, 3 had a history of Hodgkin disease, 3 had non-Hodgkin lymphoma, and 10 had mycosis fungoides; none of the control subjects reported such histories. No significant differences were observed between patients and control subjects in regard to residence or travel history or exposures to various physical, chemical, and biologic agents. A higher, although not statistically significant, percentage of patients than control subjects reported a history of radiation therapy and nonlymphoid malignant lesions. No differences were found between patients and control subjects in regard to other medical conditions or family medical history. CONCLUSIONS: Patients with lymphomatoid papulosis have a significantly increased frequency of prior or coexisting lymphoproliferative disorders, an increased frequency of nonlymphoid malignant lesions, and exposure to radiation therapy. PMID- 1451080 TI - New strategies are needed in diffuse malignant mesothelioma. AB - BACKGROUND: Medical records of 50 patients with malignant mesothelioma were reviewed to determine the clinical features and factors influencing survival. METHODS: Charts of all patients whose conditions were diagnosed as malignant mesothelioma were abstracted and analyzed by statistical software. RESULTS: The male-to-female ratio was 4:1. The age distribution was younger than 45 years of age, 10%; 45-54 years of age, 12%; 55-64 years of age, 37%; 65-74 years of age, 33%; and 75 years of age or older, 8%. Both mean and median ages were 58 years. Among the 32 patients in whom asbestos exposure was recorded, 24 had documented exposure. The sites were pleura, 73%; peritoneum, 20%; and both, 6%. The histologic types were epithelial, 51%; sarcomatous, 10%; mixed, 15%; and not specified, 24%. The stage at presentation was Stage I, 37%; II, 39%; III, 12%; IV, 6%; and unknown, 6%. The common symptoms in pleural disease were dyspnea and pain; in peritoneal disease, abdominal distension and pain were common. The median time from first symptom to diagnosis was 3 months (range, 0-23 months). The median survival after the appearance of symptoms, the diagnosis, and the treatment were 13, 10, and 8 months, respectively. CONCLUSIONS: The survival was independent of age, sex, and smoking behavior. It was longer in patients with earlier-stage disease, a good performance status, a longer duration of symptoms, an absence of pain, and who were treated with combined surgery and chemotherapy. Chemotherapy using anthracyclines yielded more remissions (9 of 21) than that using nonanthracyclines (0 of 13). The remission rate after primary chemotherapy with anthracyclines (7 of 16) may be higher than in recurrent tumor (2 of 14). In future trials, stratification into primary chemotherapy and chemotherapy of recurrent cancer is suggested. There is a need for multitechnique trials incorporating primary chemotherapy. PMID- 1451081 TI - Concomitant mucinous tumors of appendix and ovary. Result of a neoplastic field change? AB - BACKGROUND: Mucinous tumors of the appendix and ovary are known to occur together in association with pseudomyxoma peritonei. It has been postulated that this association may be attributable to the development of independent tumors or to metastasis from one site to another. METHODS AND RESULTS: This article reports two patients with concomitant mucinous ovarian and appendiceal tumors in the absence of pseudomyxoma peritonei. CONCLUSIONS: The evidence suggests that these tumors are independent primary neoplasms that develop as a result of neoplastic field change that affects colonic-type epithelium. PMID- 1451082 TI - The Clinical Oncology Career Development Award of the American Cancer Society. A 5-year evaluation. AB - BACKGROUND: In 1985, the American Cancer Society (ACS) replaced their Junior Faculty Clinical Oncology Program with the 3-year Clinical Oncology Career Development Award (COCDA). It was proposed that the longer duration and larger stipend of the COCDA would have a greater impact in encouraging promising young clinical oncologists to enter and remain in academic oncology. The COCDA was evaluated at this time to determine whether these goals had been achieved. METHODS: A questionnaire was sent to 104 of the total of 121 people who received awards in 1985, 1986, and 1987. RESULTS: A review of the 85 completed questionnaires showed that the COCDA had a significant impact on the recipients. Most have remained in academic settings and have flourished, as evidenced by their publication record and success in obtaining extramural funds, despite their clinical orientation. CONCLUSIONS: The COCDA has achieved its initial goals and will remain an important part of the professional education efforts of the ACS. PMID- 1451083 TI - The WHO Histological Typing of Odontogenic Tumours. A commentary on the Second Edition. AB - This article introduces the revised World Health Organization (WHO) classification of odontogenic tumors and jaw cysts and certain bone lesions that either are peculiar to the jaws or have distinctive features in that location. The new and revised classification is compared with the previous version, the reasons for the changes are outlined, and reference is made to a number of newly characterized lesions that have been included. PMID- 1451084 TI - Boron neutron capture therapy for cancer. Realities and prospects. AB - Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10 (10B), is irradiated with low-energy thermal neutrons (nth) to yield (4He) alpha-particles and 7Li nuclei (10B+nth-->[11B]- >4He+7Li+2.31 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of 10B and nth to individual cancer cells to sustain a lethal 10B(n, alpha) 7Li reaction. The current review covered the radiobiologic considerations on which BNCT is based, including a brief discussion of microdosimetry and normal tissue tolerance. The development of tumor localizing boron compounds was discussed, including the sulfhydryl-containing polyhedral borane, sodium borocaptate (Na2B12H11SH), and boronophenylalanine (BPA), both of which are currently being used clinically in Japan as capture agents for malignant brain tumors and melanomas, respectively. Compounds currently under evaluation, such as boronated porphyrins, nucleosides, liposomes, and monoclonal antibodies (MoAbs), were also considered. Nuclear reactors have been used as the exclusive source of neutrons for BNCT. The use of low-energy (0.025 eV) thermal neutrons and higher-energy (1-10,000 eV) epithermal beams, beam optimization, and possible alternative neutron sources (accelerators) were also discussed. Clinical studies performed in the United States during the 1950s and 1960s for the treatment of malignant brain tumors were reviewed. Current studies in Japan and future studies in Europe and the United States concerning the treatment of glioblastomas and melanomas by BNCT were discussed, as were critical issues that must be addressed if BNCT is ever to be a useful therapeutic modality. PMID- 1451085 TI - Leadership through alliances. PMID- 1451086 TI - TENS: an adjunct to analgesia. PMID- 1451087 TI - Ketamine. A solution to procedural pain in burned children. AB - Our experience has shown ketamine to be a safe and effective method of providing pain relief during specific procedures in burned children. It renders high doses of narcotics unnecessary and offers children the benefit of general anesthesia without the requirement of endotracheal intubation and a trip to the operating room. The response of parents and staff to the use of ketamine has been positive. Parents often experience feelings of guilt following injury to a child and are eager to employ methods that reduce their child's pain. So far, no parent has refused the administration of ketamine; some have even asked that it be used during subsequent procedures on their child. With adequate pre-procedure teaching, parents are prepared for the possible occurrence of emergent reactions and can assist in reorienting the child during recovery. Staff have found that the stress of doing painful procedures on children is reduced when ketamine is used. The procedures tend to be quicker and the predicament of working on a screaming, agitated child is eliminated. At the same time, nursing staff have had to get used to the nystagmic gaze of the children and accept that these patients are truly anesthetized even though they might move and talk. Despite the success we and others have had with ketamine, several questions about its use in burn patients remain unanswered. The literature does not answer such questions as: Which nursing measures reduce the incidence of emergent reactions? How many ketamine anesthetics can safely be administered to one individual? How does the frequency of administration relate to tolerance in a burn patient? Are there detrimental effects of frequent or long-term use? Clearly, an understanding of these questions is necessary to determine the safe boundaries of ketamine use in burn patients. Ketamine is not a panacea for the problem of pain in burned children. But it is one means of managing procedural pain, which is, after all, a significant clinical factor in treatment and recovery. PMID- 1451088 TI - Child sexual abuse. What parents need to know. PMID- 1451089 TI - [Routes to modify the impact of stress]. AB - The combined effects that daily frustations and tensions have upon you depend, among other factors, on the evaluation you make of the importance of your needs as well as your confidence in your abilities. This effect is equally dependent upon your evaluation of the availability, quality and adequacy of your support system. To minimize the effects of stress, it is important to develop your internal and external resources. Stress management requires more than learning relaxation techniques. It demands the development of certain attitudes that will eventually influence your entire life. This includes the development of a realistic perception of situations and demands the realization that you can only do your best, keeping in mind your knowledge, and resources as well as the context of the moment. Stress management is time management. The management of your energies is related to your resources, your values, your needs and your priorities. The bottom line is the management of your life. Daily, nurses confront the challenge of discovering their own way of gathering information, of resolving problems, of planning pleasant activities, of benefiting from those surrounding them, as well as generating ideas, thoughts and emotions. Caring for patients must also include taking care of one's self. PMID- 1451090 TI - [Family intervention according to Roy]. AB - The author presents a care plan based upon Sister Callista Roy's conceptual model, that is recognized as well suited to the family system. This, the first of two-part series, focuses on the first two steps of the care plan--the theoretical and practical aspects of data collection and data analysis. The subjects are a single mother and her son. During the first level of evaluation of the family system, the nurse observes and explores the family system's behavior as well as that of each of the family members using the four modes of adaptation: physiological needs, self-concept, role function, and interdependence relations. During the second level of evaluation, the nurse identifies observed and reported stimuli or factors within the family environment that influence observed behaviors. During the data analysis, the nurse determines if the reported or observed behaviors are adaptive or non-adaptive toward maintaining the bio-psycho social integrity of the family. The nurse also determines if the behaviors allow for achievement of identified goals. The nurse establishes links between the behaviors and the stimuli, classes and organizes the findings, and formulates an appropriate nursing care plan. Next month's article will focus on the planning, implementation and evaluation of the nursing care plan. It will focus equally on the ways in which the nurse can facilitate the family's adaptation. PMID- 1451091 TI - Role of polyamines in the growth of hormone-responsive and -resistant human breast cancer cells in nude mice. AB - Recent in vitro data suggest that at least some hormone-independent breast cancer cells exhibit increased polyamine biosynthesis and resistance to antipolyamine therapy. To address this issue under conditions of in vivo growth, we tested the antiproliferative effect of the polyamine synthetic inhibitor alpha difluoromethyl-ornithine (DFMO) on hormone-dependent (MCF-7) and -independent (MDA-MB-231, BT-20) breast cancer cell lines growing in nude mice. We observed that DFMO significantly inhibited the growth of established tumors to a similar extent in all cell lines, even though tumor regression was only observed with MCF 7 cells. DFMO, while inhibiting E2-supported MCF-7 breast cancer growth, did not inhibit E2-stimulated progesterone receptor synthesis. Cellular levels of polyamines were highest in MCF-7 cells and lowest in the BT-20 cell line. Tumor content of spermidine was similarly suppressed by DFMO treatment in the 3 cell lines, while the spermine level was unaffected. Cellular putrescine levels were suppressed in MCF-7 and BT-20 cells. Administration of DFMO prior to implantation of fragments of MCF-7 or MDA-MB-231 tumors in nude mice significantly inhibited tumor development to a similar extent. The action of DFMO seemed to be predominantly tumoristatic since new tumors develop in some mice upon discontinuation of the drug. We conclude that the hormone-independent breast cancer cell lines tested do not exhibit increased polyamine biosynthesis or resistance to antipolyamine therapy when grown in vivo in nude mice. PMID- 1451092 TI - Effects of NSAIDs on NNK-induced pulmonary and gastric tumorigenesis in A/J mice. AB - Non-steroidal anti-inflammatory drugs (NS-AIDs) are among the most widely prescribed drugs. In this study, we compared the efficacies of four NSAIDs to inhibit lung tumorigenesis in A/J mice. The tobacco-specific carcinogen, 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), was given in drinking water between week 0 and week +7. Groups of 25 mice were fed sulindac (123 mg/kg diet), ibuprofen (263 mg/kg), piroxicam (25 mg/kg) or naproxen (230 mg/kg) in AIN-76A diet from week -2 to the end of the bioassay (week +23). Sulindac was the most effective inhibitor and reduced lung tumor multiplicity by 51%. Ibuprofen and piroxicam reduced lung multiplicity by 38% and 30%, respectively. Naproxen demonstrated no inhibitory capacity. Forestomach tumor multiplicity and incidence were both reduced by sulindac and ibuprofen. Sulindac administered from week -2 to week +7 was less effective (28% inhibition) than when given throughout the bioassay. Sulindac induced more intestinal adhesions than any other NSAID and was directly related to the cumulative dose of sulindac. These results show that chemoprevention of lung tumorigenesis by NSAIDs is not limited to sulindac although it is the most effective. PMID- 1451093 TI - Increased survival of L1210 leukemic mice by prevention of the utilization of extracellular polyamines. Studies using a polyamine-uptake mutant, antibiotics and a polyamine-deficient diet. AB - When L1210 leukemia cells are inhibited in their polyamine synthesis by treatment with alpha-difluoromethylornithine (DFMO), their growth in culture is strongly suppressed. In striking contrast, the survival of L1210 leukemic mice is only marginally prolonged by DFMO treatment. This inconsistency is due to the fact, that in the mouse the tumor cells can utilize extracellular polyamines to compensate for the decrease in putrescine and spermidine synthesis caused by DFMO treatment. In the present study, we demonstrate that a reduction in the transport of polyamines into the tumor cells is a more effective means of increasing the therapeutic effect of DFMO than is a reduction in the supply of extracellular polyamines. DFMO treatment cured 30-75% of leukemic mice bearing mutant L1210 MGBGr cells deficient in polyamine uptake, but only slightly increased the survival time of leukemic mice bearing the parental L1210 cells despite the fact that the supply of extracellular polyamines was reduced (by feeding the mice a polyamine-deficient diet containing antibiotics). The effectiveness by which DFMO cured leukemic mice bearing L1210-MGBGr cells appeared to be sex dependent. Thus, 58% of the female mice, as compared to 30% of the male mice, were cured by DFMO treatment. PMID- 1451094 TI - Increased fucosylation and other carbohydrate changes in haptoglobin in ovarian cancer. AB - Cancer sera have high levels of an abnormal form of haptoglobin (Hp) that can be extracted from blood using the fucose-specific lectin, Lotus tetragonolobus. In order to investigate the carbohydrate abnormality that is responsible for this effect, the monosaccharide composition of Hp has been measured in Hp preparations isolated from blood samples of healthy women and women with ovarian cancer. The fucose content (g/100 g protein) of Hp was considerably elevated (7-fold) in ovarian cancer; whereas the concentrations of the other sugars were not significantly increased. There were significant increases in the galactose and N acetylglucosamine contents of the 'cancer' Hp if the levels were expressed relative to the mannose content. This latter finding suggests that there are more oligosaccharide branches on the 'cancer' Hp. The results indicate that Hp is extracted by lotus lectin from ovarian cancer sera because of the increased fucose levels and provide further support for a disturbance in fucose metabolism in cancer. PMID- 1451095 TI - Potentiation of mitomycin C cytotoxicity by glutathione depletion in a multi-drug resistant mouse leukemia cell line. AB - This study was undertaken to elucidate the mechanism of cross-resistance to mitomycin C (MMC) in a multi-drug resistant mouse leukemia cell line (P388/R-84). The P388/R-84 cells were 6.2-fold more resistant to MMC as compared to the sensitive cells (P388/S). Since oxygen radical formation has been suggested to be important in MMC cytotoxicity, MMC-dependent peroxidation of membrane lipids (an index of oxygen radical formation) was compared in these cell lines. MMC dependent lipid peroxidation was 2.56-fold higher using P388/S cell extract when compared to that of P388/R-84 cells. Depletion of cellular glutathione (GSH) levels in the resistant cells produced a 1.76-fold increase in MMC-dependent lipid peroxidation. MMC cytotoxicity was also increased significantly by GSH depletion in P388/R-84 cells. These results suggest that cellular resistance to MMC in P388/R-84 cells may, at least in part, be due to the reduced formation of oxyradicals in these cells. PMID- 1451096 TI - Effect of the progestagen R5020 (promegestone) and of progesterone on the uptake and on the transformation of estrone sulfate in the MCF-7 and T-47d human mammary cancer cells: correlation with progesterone receptor levels. AB - In the present study we have explored the actions of the progestagen R5020 (Promegestone: 17 alpha, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione) and progesterone on the uptake of [3H]estrone sulfate ([3H]E1S) and its conversion to estradiol (E2) by two hormone-dependent mammary cancer cell lines: MCF-7 and T 47D. R5020 or progesterone significantly decreased the uptake of [3H]E1 and its conversion to (E2). In the cells of the two lines, R5020 or progesterone (5 x 10( 6) M) decreased the E2 concentrations by 2-3 times in relation to the levels in untreated cells. E1S (1 x 10(-7) M) also increased expression of the progesterone receptor (PR) and both R5020 (5 x 10(-6) M) and progesterone (5 x 10(-6) M) blocked this stimulatory action of E1S in cells of both cell lines. As E2 is one of the main factors of cancerization in the breast and estrone sulfate is quantitatively the most important precursor of E2 in this tissue, the decrease of E2 by these progestagens could open new possibilities for the control of E2 in the breast cancer tissue. PMID- 1451097 TI - Droloxifene (3-hydroxytamoxifen) has membrane antioxidant ability: potential relevance to its mechanism of therapeutic action in breast cancer. AB - Droloxifene (3-hydroxytamoxifen), is a triphenylethylene derivative recently developed for the treatment of breast cancer. Droloxifene was found to exhibit a membrane antioxidant ability in that it inhibited Fe(III)-ascorbate dependent lipid peroxidation in rat liver microsomes and ox-brain phospholipid liposomes. It also inhibited microsomal lipid peroxidation induced by Fe(III)-ADP/NADPH. Droloxifene was a better inhibitor of lipid peroxidation than tamoxifen, but was less effective than 17 beta-oestradiol in the two microsomal systems and in the preformed liposomal system. When introduced into ox-brain phospholipid liposomes, droloxifene inhibited Fe(III)-ascorbate induced lipid peroxidation to approximately the same extent as similarly introduced cholesterol and tamoxifen, although to a lesser extent than 17 beta-oestradiol. This inhibition of lipid peroxidation by droloxifene may result from a membrane stabilization that could be associated in cancer cells with decreased plasma membrane fluidity. This mechanism may be related to the clinically important antiproliferative action of droloxifene on cancer cells. PMID- 1451098 TI - Comparison of aflatoxin B1-DNA binding and glutathione conjugate formation by liver preparations from rats of different ages. AB - The capability of the newborn rat liver to detoxify aflatoxin B1 (AFB1), a potent hepatocarcinogen is not well understood. Our present results show that immature rats are deficient in the hepatic key factors involved in biotransformation of AFB1. The activities of cytosolic glutathione S-transferases and microsomal cytochrome P-450 along with cellular glutathione (GSH) content show postnatal developmental changes. The ability of hepatic subcellular preparation from newborn rats to convert AFB1 to its reactive epoxide form, is reported for the first time in this communication. Epoxidation of [3H]AFB1 in the presence of liver microsomes from different age-groups as measured by its adduct formation to calf thymus DNA in vitro shows that newborn rats are capable of catalyzing only minimal AFB1-DNA binding compared with that of adults. Addition of cytosolic fraction of various age groups to the system suggests that young rats are less efficient in modulating the binding as compared with adults. The amount of AFB1 GSH conjugate formed is also significantly higher when adult GSH S-transferase is involved in the system. These observations show that immature liver is less efficient than a mature organ in handling a chemical carcinogen and the metabolism of AFB1 by neonatal liver differs from that in the adult. PMID- 1451099 TI - Differential induction of indoleamine-2,3-dioxygenase (IDO) by interferon-gamma in human gynecologic cancer cells. AB - Induction of indoleamine-2,3-dioxygenase (IDO) by interferon-gamma (IFN-gamma) is thought to be one mechanism underlying IFN-gamma's antineoplastic properties. Since clinical trials with IFN-gamma have yielded variable efficacy in treating cancers of gynecological origin, we tested the effects of IFN-gamma on cell growth and IDO activity in cell lines from seven gynecologic and five breast cancers. At a dose of 250 IU/ml, IFN-gamma suppressed cell growth and induced IDO activity in one cervical (C41), one vulva (A431), one breast (HS578T) and two ovarian (OVCAR-3, CAOV-3) cancer cell lines. Differing inhibition of cell growth, but with no induction of IDO activity, was found with IFN-gamma treatment of the other cell lines. PMID- 1451100 TI - Transcriptionally active non-ligand binding oestrogen receptors in breast cancer. AB - Data were obtained on soluble oestrogen (ER) and progesterone (PR) receptors from 273 primary breast tumours, using an enzyme immunoassay (EIA) and ligand binding assay with dextran-coated charcoal (DCC) or isoelectric focussing separations. The p29 and total cathepsin D content was also assayed in the same samples. Tumours expressing ER (by either steroid binding assay or EIA) had higher levels of p29 than those which did not express the receptor (P < 0.0001). Moreover, tumours co-expressing ER, PR and p29 appeared to have higher levels of cathepsin D than those which were negative for at least one protein (P < 0.0001). Twenty out of the 273 human breast cancer samples, containing a level of ER positive by EIA, which did not bind labelled oestradiol, were identified; isoelectric focussing showed that such a receptor was also unable to bind hydroxytamoxifen. These tumours did not significantly differ from those in the whole population in their capacity to express ER (positive by EIA), PR, p29 and cathepsin D. It was concluded that the EIA can detect both a ligand binding ER and a receptor which is able to initiate PR transcription but does not bind radio-labelled ligands in vitro; such a receptor could have a bearing on the variability of tumour response to endocrine therapy. PMID- 1451101 TI - Isolation of a 18,000-Da molecular weight form of parathyroid hormone-related protein from the rat Walker carcinosarcoma 256. AB - The hypercalcaemic Walker carcinosarcoma 256 is a rat model for humoral hypercalcaemia of malignancy (HHM). Tumour products such as parathyroid hormone related proteins (PTHRP) and various growth factors appear to be responsible for this syndrome. Recently, PTHRP immunoreactivity has been detected in the conditioned medium of Walker tumour cells. The present report describes the isolation of a 18,000-Da molecular weight form of PTHRP from Walker tumour homogenates, by using a relatively simple immunoaffinity purification method. Our results suggest that this PTHRP form is similar to that purified from other HHM related tumours. PMID- 1451102 TI - The distribution of the tumour photosensitizers Zn(II)-phthalocyanine and Sn(IV) etiopurpurin among rabbit plasma proteins. AB - Zn-phthalocyanine (ZnPc) and Sn-etiopurpurin (SnET2) incorporated in unilamellar liposomes or solubilized in a Cremophor-EL emulsion have been incubated in vitro with rabbit plasma or intravenously administered to rabbits. Ultracentrifugation and chromatographic analysis of the plasma showed that ZnPc and SnET2 are mainly released to lipoproteins; within the lipoprotein family, both dyes are preferentially bound by low-density (LDL) and high-density (HDL) lipoproteins. The amount of dye bound with these two lipoprotein classes was related to their relative concentration in the plasma; in most cases a larger amount of photosensitizer was bound to HDL as compared to LDL on a protein concentration basis. PMID- 1451103 TI - Investigation on glutamine amidohydrolase (EC 3.5.1.2) and glutamine aminotransferase (EC 2.5.1.15) activity in liver and plasma of EAC-bearing mice following glutaminase therapy. AB - The anti-neoplastic activity of bacterial glutaminase on Ehrlich ascites tumor bearing mice was studied by determining the reduction in the tumor cell count and extension of life span of the host after therapy. The therapeutic effect of glutaminase in relation to change in activity of glutaminolytic enzymes (glutamine amidohydrolase (GNase) and glutamine aminotransferase (GAt)) in liver and plasma were also studied. Bacterial glutaminase was shown to be effective in lowering the tumor burden with increased life span of the host. Glutamine amidohydrolase activity in the liver and plasma was raised significantly with increased tumor burden, whereas GAt activity remained unchanged. Following glutaminase therapy, this high level of GNase activity decreased in comparison to the untreated control. These changes were not seen when normal mice were treated with the same enzyme. Thus alteration in the enzyme levels, particularly GNase was observed to have some correlation with progression of the tumor growth. PMID- 1451104 TI - Dietary retinoids are essential for skin papilloma formation induced by either the two-stage or the complete tumorigenesis model in female SENCAR mice. AB - Our previous work has shown that dietary retinoic acid (RA) is necessary for skin tumor formation induced by the two-stage protocol with the initiator 7,12 dimethylbenz[a]anthracene (DMBA) and the promoter 12-O-tetradecanoyl phorbol-13 acetate (TPA) (De Luca et al., Cancer Res., 36 (1976) 2334-2339). Here we report that retinoids are required for tumorigenesis by the two-stage as well as by the complete tumorigenesis protocol. Mice were treated with a single dose of DMBA (20 micrograms), followed by 20 applications of TPA (2 micrograms), or by 20 applications of DMBA (25 micrograms for 2 weeks and 51 micrograms thereafter). Regardless of the tumor induction protocol, tumor formation was inhibited by vitamin A-deficiency, while RA (3 micrograms/g of diet) or retinyl palmitate (RP, 6 micrograms/g) supplementation permitted the appearance of tumors. In addition, in comparison to the purified diets and regardless of their RA levels, the non purified Purina chow diet enhanced tumor yield especially in the two-stage tumorigenesis protocol. This effect was less striking in mice with tumors induced by the complete tumorigenesis protocol. In summary, dietary retinoids are essential for skin tumor formation induced either by the two-stage or the complete tumorigenesis protocol. PMID- 1451105 TI - Effect of dietary oxidized cholesterol on azoxymethane-induced colonic preneoplasia in mice. AB - The effect of cholesterol and oxidized cholesterol on azoxymethane-induced colonic preneoplasia was evaluated in C57BL/6J and BALB/cJ mouse strains. Mice were fed either a control AIN 76 semisynthetic diet or the control diet supplemented with 0.1% or 0.3% cholesterol, or 0.1% or 0.3% oxidized cholesterol for an 8-week period. For the first 4 weeks of the experiment, mice received weekly injections of azoxymethane (5 mg/kg body weight). Dietary cholesterol increased fecal concentrations of neutral and acid sterols. A dose-response relationship was observed in both mouse strains between the level of dietary cholesterol or oxidized cholesterol and formation of preneoplastic aberrant crypt foci. Enhanced cell proliferation along with alterations in several crypt morphometric parameters were also observed. These anomalies were enhanced to a greater extent by oxidized cholesterol. This data shows a very strong effect of cholesterol in enhancing the development of preneoplastic lesions in chemically induced cells. It also demonstrated that the state of oxidation of cholesterol influences colonic preneoplasia. This factor has been overlooked in previous animal experiments. PMID- 1451106 TI - Species and sex differences of aflatoxin B1-induced glutathione S-transferase placental form in single hepatocytes. AB - Species and sex differences of aflatoxin B1 (AFB1)-induced glutathione S transferase placental form (GST-P) positive single hepatocytes have been investigated 48 h after an intraperitoneal injection of AFB1 to young male and female Fischer rats (2 mg AFB1/kg body wt) and male Syrian golden hamsters (6 mg AFB1/kg body wt). The presence of GST-P positive hepatocytes was examined by the immunohistochemical method. Male rats formed three times as many AFB1-induced GST P positive hepatocytes as females. Pretreatment of both male and female rats with an inhibitor of GSH synthesis, buthionine sulfoximine (BSO) (4 mmol/kg body wt), 2 h and 4 h before AFB1 injection increased AFB1-induced GST-P positive hepatocytes by about 120% above the controls. Male hamsters formed several-fold less AFB1-induced GST-P positive hepatocytes than male rats. Pretreatment with BSO did not increase AFB1-induced GST-P positive hepatocytes in hamsters even though it produced an increase in hepatic necrosis. It appears that GSH and GSH S transferases play an important role in modulating hepatic AFB1-DNA binding and AFB1-induced GST-P positive hepatocytes in rats and hamsters. PMID- 1451107 TI - Bcl-2: an antidote to programmed cell death. AB - The maintenance of homoeostasis in normal tissues reflects a balance between cell proliferation and cell death. The importance of both positive and negative regulators of cell growth has been well documented in neoplasia. bcl-2 argues for the existence of a new category of oncogenes, regulators of programmed cell death. The bcl-2 gene was identified at the chromosomal breakpoint of t(14;18) bearing B cell lymphomas. Bcl-2 has proved to be unique among proto-oncogenes in being localized to mitochondria and in blocking programmed cell death rather than affecting proliferation. In adults, bcl-2 is topographically restricted to progenitor cells and long-lived cells in tissues characterized by apoptotic cell death. Bcl-2 is confined to the zones of surviving B cells in germinal centres. Within thymus, bcl-2 is present in the surviving mature thymocytes of the medulla but absent from the majority of immature cortical thymocytes, most of which die by apoptosis. Transgenic mice that overexpress bcl-2 in the B cell lineage demonstrate extended cell survival and prolonged immune responses and indicate a role for bcl-2 in B cell memory. Transgenic models that overexpress bcl-2 in the thymus have expanded the involvement of bcl-2 to multiple apoptotic pathways and indicate its involvement in thymocyte maturation. Moreover, the development of tumours in transgenic mice that overexpress bcl-2 indicates the potential importance of oncogenes in interfering with programmed cell death. Alterations in genes that regulate cell death may prove to be key events in neoplasia, extending the life span of cells and thus increasing their opportunity to acquire additional genetic aberrations. PMID- 1451108 TI - Oncogene co-operation in leukaemogenesis. AB - The multistep development of haematopoietic malignancies, like other neoplasms, reflects sequential mutations that either activate proto-oncogenes or disrupt tumour suppressor genes. In a few spontaneous leukaemias or lymphomas, more than one mutation has now been identified, and the experimental analysis of oncogene co-operation is advancing rapidly via retroviral gene delivery and characterization of transgenic mice bearing oncogenes. In transgenic models, tumorigenesis can be accelerated by introducing another oncogene or by using a retrovirus as an insertional mutagen to identify cellular genes that collaborate with the transgene. Leukaemogenesis can be promoted by some ten pairs of oncogenes. The myc nuclear oncoprotein, for example, can collaborate with cytoplasmic oncoproteins such as ras, raf, bcl-2, pim-1 and v-abl, as well as with nuclear products such as bmi-1 or the tumour suppressor p53. The genes in such partnerships seem to provide complementary functions. For example, myc seems to prevent cells from becoming quiescent, whereas bcl-2 blocks programmed cell death; and others, for example ras, may diminish growth factor requirements. The products of genes that collaborate may lie on separate signal transduction pathways, leading to distinct nuclear targets. Key targets are postulated to be regulators of the cell cycle, especially the cyclins and associated kinases that govern progression in the G1 phase. PMID- 1451109 TI - Deletions of chromosome 5 in malignant myeloid disorders. AB - Loss of a whole chromosome 5 or deletion of 5q are recurring abnormalities in malignant myeloid neoplasms. Chromosomal loss or deletion are the hallmarks of tumour suppressor genes, suggesting that a gene(s) located on 5q may function as a leukaemia suppressor gene. To determine the location of genes on 5q that may be involved in myeloid leukaemogenesis, we examined the breakpoints of the del(5q) in a series of 117 patients with malignant myeloid diseases. By comparing the breakpoints, we identified a small segment of 5q, consisting of band 5q31, that was deleted in each patient. This segment has been termed the critical region. A striking number of genes encoding haematopoietic growth factors have been mapped within or adjacent to the critical region. These include the genes encoding CSF 2, IL-3, IL-4, IL-5 and IL-9. By using fluorescence in situ hybridization, we have refined the localization of these genes to 5q31.1. To facilitate the identification of a tumour suppressor gene on 5q, we are currently preparing a physical map of 5q31. With FISH analysis of a series of cosmid and phage clones, we identified a number of clones within 5q31. By hybridizing these probes to metaphase cells with a del(5q) involving proximal or distal breakpoints within 5q31, we have narrowed the critical region to a small segment of 5q31 containing eight of the cosmids. In addition, we found that the five growth factor genes are excluded from this region. We have used dual colour FISH to determine the order of these cosmids, the order of the known genes mapped to 5q23-33 and the relationship of these genes to the critical region. To date, mutations of these genes in leukaemia cells have not been identified. The clinical features of myeloid diseases associated with a del(5q) are variable (RA 5q- syndrome v. AML); thus, once the involved gene is identified, it will be important to determine whether the same gene is involved in both types of myeloid disorders. PMID- 1451110 TI - Murine models of normal and neoplastic human haematopoiesis. AB - The ability to transplant human haematopoietic cells into immune deficient mice provides a unique opportunity for studying the organization and regulation of the human stem cell developmental program. One challenge for the future will be to reconstitute mice with functional cells of all lineages. The creation of animal models of many haematopoietic diseases should revolutionize the development and testing of novel therapeutic strategies. Significant progress has been made in establishing models of human neoplastic diseases such as leukaemia and lymphoma. Although the number of patients examined is still small, it appears that there may be a correlation between growth in immune deficient mice and clinical outcome. Future studies should examine the range of diseases that grow in mice and whether in vivo assays have prognostic value clinically. These leukaemia models, in conjunction with high efficiency gene transfer techniques, offer a powerful approach to examine the biological consequences of expressing oncogenes or other key regulatory genes on human leukaemic transformation and progression. PMID- 1451111 TI - The interaction of the erythropoietin receptor and gp55. AB - Friend virus induced erythroleukaemia can be conveniently divided into a first stage and a second stage. The first stage results from the mitogenic stimulation of EPO-R by gp55. In the second stage, multiple proviral integrations appear to result in further transformation of the SFFV infected erythroblast to a leukaemogenic state. The first stage results from EPO-R activation. After retroviral entry, mediated through an unknown receptor, and after cDNA synthesis and proviral integration, viral proteins are synthesized. Gp55 binds and activates EPO-R. A small but measurable amount of gp55-EPO-R complex is transported to the cell surface (Casadewall et al, 1991). In the presence of helper virus, the defective SFFV genome is packaged and released for subsequent rounds of infection. During the first stage, erythroblasts proliferate but are not tumorigenic. During the second stage of Friend disease, subsequent infections result in further proviral integrations in the host genome. Some of these integrations result in increased Spi-1 expression, whereas others result in decreased p53 expression. These events appear to account for the leukaemogenic properties of cells at this stage, 4-6 weeks after the initial SFFV infection. The interaction between EPO-R and gp55 persists at this later stage, although its contribution to the malignant phenotype of the MEL cells is not known. The sequence of events during stage 1 and stage 2 does not appear to have absolute requirements. Starting with IL-3 dependent immortalized Ba/F3 cells, which already have some unknown proliferative mutation (Mathey-Prevot et al, 1986), gp55 and EPO-R can subsequently be introduced, resulting in tumorigenicity (Li et al, 1990). The primary focus of this review has been the early mitogenic stage of Friend disease. Several concepts have emerged regarding the interaction between gp55 and EPO-R. The interaction between the polypeptides is highly specific, occurs in the extracytoplasmic regions and the transmembrane region of the polypeptides and occurs within the same cell, not via cell-cell contact. Both EPO and gp55 activate EPO-R, via different binding sites, resulting in increased cellular tyrosine kinase activity. The first stage of Friend disease is an example of how a non-oncogene bearing retrovirus can induce leukaemia. The env gene of the SFFV is not a classical oncogene. It does not appear to be derived from a normal cellular proto-oncogene. The interaction of gp55 and EPO-R therefore supports the "receptor mediated leukaemogenesis" hypothesis (McGrath and Weissman, 1978, 1979).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1451112 TI - The haematopoietic stem cell and its clonal progeny: mechanisms regulating the hierarchy of primitive haematopoietic cells. AB - Transplantation and marking studies have provided an accurate description of various aspects of developmental and proliferative behaviour of totipotent haematopoietic stem cells. In particular, the remarkable ability of different clones to contribute to all lineages in a continuous, stable and long term manner is a hallmark of stem cell behaviour. Taken together, in vivo reconstitution experiments also provide the basis for a model of stem cell regulation that incorporates stochastic and non-stochastic components. More recent approaches provide optimism that many descriptive aspects of stem cell biology will soon be supported by elucidation of molecular mechanisms. PMID- 1451113 TI - The bcr-abl gene in chronic myelogenous leukaemia. AB - The observation made over 30 years ago that the Philadelphia chromosome is present in nearly all patients with CML led to the identification of a novel fusion gene bcr-abl. In the past few years, the biochemical and biological properties of bcr-abl have been extensively explored. Bcr sequences appear to activate c-abl for transformation by binding to the SH2 domain of c-abl in an intramolecular interaction, presumably interfering with the adjacent SH3 regulatory domain. Upon introduction into bone marrow cells, bcr-abl can cause acute or chronic leukaemias in mice and can stimulate the growth of many cell types, including multipotent stem cells, in vitro. Although their growth is stimulated, these cells are not fully malignant blastic leukaemias. The molecular events that occur during the progression to blast crisis of CML remain largely undefined, but existing animal models and in vitro culture systems will be useful for identifying or testing candidate genes. The study of tyrosine kinase oncogenes in general will probably lead to the identification of relevant bcr-abl substrates. The elucidation of these molecules as well as more downstream events in the bcr-abl signalling pathway offers the hope for novel therapeutic interventions to control Philadelphia chromosome leukaemias. PMID- 1451114 TI - Avian erythroblastosis: a model system to study oncogene co-operation in leukemia. AB - Avian erythroblastosis virus, AEV-ES4, provides an ideal in vitro system to study oncogene co-operation in the development of erythroid leukaemias in chickens. Two oncogenes that use distinct signal transduction pathways have been identified; these act to produce a highly malignant phenotype and are an oncogenic version of a plasma membrane growth factor receptor that regulates haematopoietic progenitor self renewal and a mutated version of a transcription factor that suppresses specific gene expression. These two diverse types of oncogenes act together to generate a more malignant phenotype than would be expected merely from a summation of the individual oncogene effects. The aspects of normal growth control and the regulation of differentiation, which are altered in this system to generate the leukaemic phenotype, include changes in the balance between proliferation versus maturation, altered expression of differentiation genes and changes in growth factor responsiveness. These are exactly those features that are altered in human leukaemias. Thus, the avian leukaemia virus model has taught us important lessons that will help us to understand the basic molecular mechanisms that give rise to human leukaemia. PMID- 1451115 TI - Role of rel family genes in normal and malignant lymphoid cell growth. AB - The rel family of genes encodes transcription factors, such as the v-rel oncoprotein and cellular transcription complexes (eg NF-kappa B), consisting of c rel and related polypeptides. The expression of these genes is correlated most closely with lymphoid cell differentiation and growth stimulation in a variety of cell types. Similarly, rel family proteins control a number of genes involved in lymphoid cell growth and differentiation. Thus, it is not surprising that mutations in rel genes have been implicated directly and circumstantially in a number of lymphoid malignancies, as have a number of other cellular and viral transcription factors (see also Cleary M, Hayman M and Beug H, this issue and reviewed in Rabbitts, 1991). In addition, rel proteins are likely to be involved in T cell diseases caused by the human retroviruses HTLV-I and HIV-1. Therefore, rel proteins could serve as targets for anti-viral or anti-cancer therapies. PMID- 1451116 TI - Transcription factors in human leukaemias. AB - At the present time, two general mechanisms account for deregulation and subsequent oncogenic conversion of transcriptional proteins in human leukaemias. One involves quantitative alterations in expression, suggesting that activity of the involved factors is primarily controlled by their accessibility within the cell. Neoplastic transformation may result from excessive expression or, conversely, complete loss of functional products (eg tumour suppressor proteins not described here). The second mechanism involves mutation by protein fusion (or truncation) and illustrates the modular composition of transcriptional proteins. The loss or inappropriate combination of specific modules creates chimaeric proteins with presumably altered transcriptional properties that may contribute to the neoplastic phenotype. Both mechanisms underscore the importance of cognate interactions, particularly heterodimerization between various transcriptional proteins with other members of the transcription complex. Future efforts will continue to focus on the interactions of oncogenic transcription factors with other cellular proteins and their biologically relevant target genes. PMID- 1451117 TI - Echocardiographic and ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension. AB - High-resolution ultrasonography is a noninvasive technique that allows to investigate the cardiovascular system, in particular the wall thickness and the lumen diameter of the arteries with accuracy and reproducibility. We measured the intima-media thickness of the common carotid artery (CCA) and of its bifurcation (BIF) in 40 patients with essential hypertension, 20 of them with left ventricular hypertrophy (LVH; age 42 +/- 10 years) and 20 without LVH (age 44 +/- 12 years); no other major cardiovascular risk factor was present in all the patients. Both carotid axes have been scanned from different views (anterior, lateral, posterior) on a transversal and longitudinal section using a high resolution steerable linear array of 5.0 MHz. Carotid diameter and thickness were measured in the longitudinal section. CCA parameters were assessed 20 mm caudally to the flow divider. In patients with LVH, blood pressure (172 +/- 21/108 +/- 9 mm Hg) and left ventricular mass index (156 +/- 38 g/m2) were significantly (p < 0.01) higher than in patients without LVH (blood pressure: 158 +/- 11/99 +/- 12 mm Hg; left ventricular mass index: 98 +/- 10 g/m2), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness of both the CCA and BIF was significantly higher in the hypertensives with LVH (CCA: 0.85 +/- 0.02 vs. 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 vs. 0.70 +/- 0.03 mm, p < 0.01). There was a statistically significant correlation between the carotid wall thickness and the left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451118 TI - Loss of nocturnal increase in plasma concentration of atrial natriuretic peptide in hypertensive chronic renal failure. AB - Diurnal change of plasma atrial natriuretic peptide (ANP) concentration was investigated in 12 patients with hypertension due to chronic renal failure (CRF) and in 12 patients with essential hypertension (EH) of comparable degree. Blood pressure (BP) monitoring was performed at 15-min intervals, while peripheral blood samples were obtained at 4-hour intervals starting from 8.00 h. The mean 24 hour plasma levels (+/- SEM) of ANP were 24.3 +/- 1.8 pmol/l in EH and 23.4 +/- 1.2 pmol/l in CRF. In EH, plasma ANP concentration was highest at 4.00 h (33.5 +/ 0.8 pmol/l) and lowest at 16.00 h (15.5 +/- 0.6 pmol/l). In CRF, no significant circadian change was present (22.2 +/- 3.1 and 20.4 +/- 3.6 pmol/l, respectively), and the nocturnal fall in BP was lost. Our data demonstrate that in CRF the loss and possible reversal of the nocturnal decline in BP is associated with the disappearance of any significant circadian variation in the circulating concentrations of ANP. These findings suggest a role for ANP in the alteration of BP variability of CRF, possibly mediated by autonomic dysfunction, and are further evidence for the existence of a relation between the circadian rhythms of ANP and BP. PMID- 1451119 TI - Gallopamil in chronic stable angina: antianginal effect and mechanism of action. A randomized, placebo-controlled, double-blind, cross-over trial. AB - A double-blind, placebo-controlled, cross-over trial of oral gallopamil was performed in 10 patients with stable angina. Gallopamil significantly increased mean exercise time and 1-mm ST time. The rate-pressure product was increased at 1 mm ST time, but unmodified at the highest comparable work load and at peak exercise. The ST segment depression was significantly reduced both at the highest comparable work load and at peak exercise. Gallopamil proves safe and effective; the mechanism of its anti-ischemic effect seems to be due both to an increase in myocardial oxygen supply and to a reduction in myocardial oxygen demand. PMID- 1451120 TI - Role of adrenal androgens in the development of arteriosclerosis as judged by pulse wave velocity and calcification of the aorta. AB - To evaluate the role of adrenal androgens in the development of arteriosclerosis, serum dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), aortic calcification and pulse wave velocity (PWV) were measured in 69 males and 119 females without overt cardiovascular disease. The steroids decreased with age in both sexes, and the reduction was significantly steeper in younger (< or = 40 years) than in older (> 40 years) subjects only in females. When adjusted for age, the steroids were significantly lower in subjects with aortic calcification than in those without it, and the PWV was significantly slower in the latter. Adrenal androgens appear to retard the development and/or progression of arteriosclerosis. PMID- 1451121 TI - Fibrinogen values in patients with and without restenosis following percutaneous transluminal coronary angiography. AB - Fibrinogen has turned out to be an independent risk factor for coronary heart disease (CHD). It is not known whether or not this parameter could be a prognostic factor for restenosis following percutaneous transluminal coronary angioplasty (PTCA), which represents the main problem limiting the long-term efficacy of this procedure. Therefore, we studied fibrinogen concentrations in a series of 50 males (mean age: 55, range: 38-70 years) with CHD and successful PTCA. Follow-up coronary angiography was performed 12 months following PTCA. Twenty-two patients had restenosis, and 28 patients were without restenosis. Both groups did not differ significantly in medical history (smoking habits, hypertension, positive family history for cardiovascular diseases), in routine lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoproteins A1 and B). Fibrinogen values were 405 +/- 128 mg/dl (range: 202-725) in patients with restenosis and 352 +/- 94 mg/dl (range: 187-568) in patients without restenosis (not significant). Elevated fibrinogen levels of more than 400 mg/dl were found in 8 patients in each group. Although fibrinogen is a proven marker for CHD in men, fibrinogen is not a risk factor for restenosis following PTCA. PMID- 1451122 TI - Hemodynamic effects of ibopamine on the pulmonary circulation and right ventricular performance in patients with chronic obstructive pulmonary disease. AB - We have studied the effects of ibopamine, an oral dopamine derivative, on pulmonary hemodynamics and blood gas values when given as a single oral dose (100 mg) to patients with severe hypoxic chronic obstructive pulmonary disease. A small but significant increase in mean pulmonary arterial pressure from 29 +/- 8 to 32 +/- 7 mm Hg (p < 0.01) was noted 30 min after ibopamine was given associated with a small increase in cardiac index. No other consistent hemodynamic changes were observed, and no alteration in blood gas values or oxygen saturation occurred. These results do not indicate a role for ibopamine in the treatment of patients with hypoxic chronic obstructive pulmonary disease and pulmonary hypertension, but, in addition, do not indicate any major deleterious effects of ibopamine on pulmonary hemodynamics or blood gas values in such patients. PMID- 1451123 TI - Hemodynamic effects and pharmacokinetics of long-term therapy with ibopamine in patients with chronic heart failure. AB - To evaluate the attenuation of the effectiveness of long-term ibopamine therapy, ibopamine was administered in single doses of 100 and 200 mg to 10 patients with chronic heart disease. The hemodynamic studies using Swan-Ganz catheter and pharmacokinetic studies were carried out. Ibopamine was found to increase cardiac output and stroke index and to decrease systemic vascular resistance in this acute study. Six patients underwent long-term therapy with the drug and were evaluated for the development of tolerance. Three out of 5 patients experienced an improvement in NYHA functional class after 12-23 weeks of treatment. There was no attenuation in the effects of ibopamine on hemodynamics, pharmacokinetic parameters remained almost unchanged, and tolerance was not observed. These results suggest that ibopamine is useful as an orally administered anti-heart failure drug. PMID- 1451124 TI - Difference in the residual left ventricular pump function between anterior and inferior myocardial infarctions. AB - To evaluate the left ventricular regional ejection fraction (EF) of noninfarcted area in relation to the left ventricular end-diastolic volume (EDV) in patients with recent myocardial infarction (MI), 75 patients with Q-wave MI (anterior: 51 patients; inferior; 24 patients) were studied. The regional EF of noninfarcted area was obtained by radionuclide angiocardiography 4 weeks after the onset of MI and was used to estimate the left ventricular regional function of the noninfarcted area. Peak creatine kinase and QRS scores were not significantly different between anterior and inferior MI in each left ventricular EDV (EDV < or = 100, 101-139 and > or = 140 ml). Global EF and regional EF of noninfarcted area in anterior MI with left ventricular EDV > or = 140 ml was significantly lower than in those with EDV < or = 139 ml (p < 0.01), whereas there were no significant differences in global EF and regional EF of noninfarcted area in the three groups of left ventricular EDV in inferior MI. Thus, the effect of left ventricular EDV on regional EF of noninfarcted area and on the total cardiac performance was more important in anterior than in inferior MI, because a similar degree of left ventricular dilatation resulted in more severe derangements after anterior MI. PMID- 1451125 TI - Risk stratification after acute myocardial infarction by means of echocardiographic wall motion scoring and Killip classification. AB - In order to perform risk stratification, 195 consecutive, unselected patients with acute myocardial infarction (AMI) underwent independent echocardiographic and clinical evaluation of their left ventricular function by means of the wall motion index (WMI) and Killip classification 5 days after AMI. The patients were prospectively allocated to a low, medium or high risk class depending on WMI alone, and the 1-year mortality in these classes was 2, 34 and 37%, respectively (p < 0.0001). The 1-year mortality of the patients in Killip class I, II, or III and IV was 6, 26 and 48%, respectively (p < 0.00001). The number of patients allocated to the low risk group by means of WMI was 87, and the number of patients in Killip class I was 86. Since these groups were not identical, a total of 103 patients, i.e. 53% of the study population, could be identified as low risk patients regarding 1-year mortality 5 days after AMI, when WMI and Killip classification were used in combination. We conclude that the combination of echocardiographic and clinical evaluation of left ventricular function after AMI provides a strong and yet very simple procedure to identify low risk patients, which could be easily implemented in the routine work of coronary care units. PMID- 1451126 TI - Electrocardiographic Q-waves inconstancy during thrombolysis in acute anterior wall myocardial infarction. AB - It is the purpose of this paper to describe the electrocardiographic inconstancy of Q-waves during administration of thrombolytic therapy. This was documented in four patients given streptokinase early in the course of anterior wall myocardial infarction. Understanding the pathogenesis of sequential dynamic variations of Q waves in this setting may offer important insights into coronary physiology and management of acute coronary events. We discuss the possible explanations for such changes with respect to tissue viability, dynamic vascular changes and electrophysiological properties of the reperfused infarcted myocardium. PMID- 1451127 TI - Progression of systolic dysfunction correlated with the ultrasonographically assessed myocardial tissue damage in patients with dilated cardiomyopathy. AB - An echocardiographic follow-up study was performed in 59 patients with dilated cardiomyopathy to characterize the relationship between left ventricular systolic dysfunction and the myocardial tissue character assessed by echocardiographic myocardial gray level distributions. All the selected patients were divided into two groups; those with (group A) and those without (group B) progressive systolic dysfunction. In group A, the ejection fraction decreased from 47 +/- 5 to 23 +/- 4% (p < 0.05) during the follow-up period. The histogram of the myocardial gray level distribution became wider, less peaked and more right-sided in those patients. The relative echo intensity of the myocardium increased from 1.29 +/- 0.19 to 1.60 +/- 0.18 (p < 0.01). In group B, however, neither the shape of the gray level distribution nor ejection fraction changed during the same follow-up period. The relative echo intensity did also not change. Our present results suggested that some of the patients with dilated cardiomyopathy showed progressive systolic dysfunction with extensive myocardial tissue damage. PMID- 1451128 TI - Effects of a 1-year exercise training program on myocardial ischemia in patients after myocardial infarction. AB - To determine the effects of exercise training on exercise-induced ischemia in patients following myocardial infarction, the experience of 13 patients with exercise-induced ST depression, who were moderate-to-high intensity trained for 1 year, has evaluated. After training, the maximum ST depression was significantly less (1.9 +/- 0.8 vs. 1.1 +/- 0.8 mm; p < 0.01), despite an increased maximal rate-pressure product (RPP; heart rate x blood pressure/100; 241.3 +/- 44 vs. 262.0 +/- 58; p < 0.01). For the onset of 0.1 mV of ST depression, we found a significant increase in RPP from 204.1 +/- 34.7 to 234.1 +/- 49.4 (p < 0.01) and also in heart rate (117.1 +/- 15.1 vs. 125.1 +/- 21.7 b.p.m.; p < 0.05), blood pressure (167.6 +/- 18 vs. 180.3 +/- 18 mm Hg; p < 0.01) and workload (93.8 +/- 17.4 vs. 121.1 +/- 23.2 W; p < 0.01). The relationship between ST depression and RPP (RPP/STmax) was favorably modified after training. The ratio RPP/STmax improved significantly from 143.6 +/- 49.4 to 209.1 +/- 69.5 (p < 0.0001). These findings support the hypothesis that a 1-year moderate-to-high training program in some patients following myocardial infarction can elicit adaptations that may well be attributed, at least in part, to an improvement in coronary blood flow. PMID- 1451129 TI - Menopause-related changes in left ventricular function in healthy women. AB - Using technetium scans, this study was aimed at examining possible changes in left ventricular function related to the natural process of cessation of ovarian estrogen production. Fourteen healthy postmenopausal women, divided into two groups according to the time-lapse from menopause (A > 3 years; B < 5 years), underwent a technetium heart scan. The two groups did not differ in heart rate, blood pressure, double product, systemic vascular resistance and cardiac index. The mean end-systolic volume in group A was 14.9 and 25.7 ml/m2 in group B (p = 0.003). The mean pressure/volume ratio was significantly higher in group A than in group B (8.6 vs. 4.7 mm Hg/ml/m2, p = 0.02). Peak ejection rate and peak filling rate were also significantly greater in group A compared to group B (3.3 vs. 2.8 end-diastolic volumes/s, p = 0.02; 2.8 vs. 2.1 end-diastolic volumes/s, p = 0.001, respectively). Our findings suggest that women at an early phase of menopause have a higher degree of myocardial contractility than women of a similar age whose menopause is of longer duration. PMID- 1451130 TI - Physical rehabilitation in coronary patients who have suffered from episodes of cardiac failure. AB - The effects of bicycle training for 5 weeks were evaluated in 12 patients after myocardial infarction with left ventricular dysfunction (left ventricular ejection fraction < 40%) and at least one episode of cardiac failure in the past. The patients were divided into two groups of six according to the Weber classification: Group B (VO2/kg/min: 16-20) and Group C (VO2/kg/min: 10-15). Cardiopulmonary and hemodynamic parameters were evaluated during a maximal exercise test and a simultaneous catheterization of the right side of the heart before and after the training. An increase in the capacity for work was recorded in Group B (p < 0.02), while Group C remained unchanged. A statistically significant increase in minute ventilation (p < 0.05) and VO2/kg/min (p < 0.0006) was recorded in Group B. Group C showed an increase in the mean pulmonary arterial pressure (p < 0.03). All of the other parameters remained unchanged after training. We conclude that physical rehabilitation improves the tolerance to exercise in patients with a mildly depressed cardiac function (Group B) but not in patients with a very depressed cardiac function (Group C). PMID- 1451131 TI - Endomyocardial biopsies in chronic chagasic cardiomyopathy. Immunohistochemical and ultrastructural findings. AB - Mononuclear cellular infiltrates and extensive fibrosis, with or without apical ventricular aneurysms, are the usual morphological findings in chronic chagasic cardiomyopathy. These lesions are thought to be mediated by immune phenomena rather than by continuing parasitic invasion of the heart. In the present report, we correlated clinical, immunohistochemical and ultrastructural findings in 30 endomyocardial biopsies from patients with chronic chagasic cardiomyopathy. In 12 of these biopsies, immunocytochemical techniques were used to identify and count leukocytes (common leukocyte antigen, CLA), T lymphocytes (UCHL-1 antibody) and B lymphocytes (L-26 antibody). The biopsy specimens showed variable degrees of myocardial hypertrophy and mononuclear infiltrates. No tissue forms of trypanosomes were found. The endocardium averaged 24 +/- 12.6 microns (mean +/- SD) in thickness. The mean myocyte diameter was 20 +/- 7.33 microns. The hearts were severely fibrotic containing a mean of 24.1 +/- 12.8% of fibrous tissue (range 8.2-49%), mast cells were scarce. Mononuclear cell infiltrates were found in 25 of the 30 biopsies. In 12 biopsies, immunohistochemical studies showed that the majority of the lymphocytes were T lymphocytes and associated with necrotic or degenerating myocytes. 10 of the 12 biopsy samples showed 5 or more CLA positive mononuclear cells/high power field. In these 10 patients, T and B lymphocytes represented 32 and 13% of the total mononuclear infiltrating cells, respectively. The remaining cells were monocytes and macrophages. PMID- 1451132 TI - Physiological features of pericardial constriction in the absence of pericardial disease. AB - To sustain a clinical diagnosis of constriction it is classically held that the fibrous pericardium must be thickened and adherent to the surface of the heart. A case is presented in which leukaemic infiltration of the fat overlying the myocardium resulted in the physiological features of constriction, although all layers of the pericardium itself were normal. Constriction is thus a physiological diagnosis; it may develop in the absence of the classical anatomical findings. PMID- 1451133 TI - Variability in the transtricuspid gradient by continuous wave Doppler echocardiography. AB - In order to examine the day-to-day variability in the tricuspid regurgitant velocity jet and to determine the degree of physiological changes under exercise and volume loading, repeated echo cardiographic Doppler measurements in 1 single subject were performed. PMID- 1451134 TI - The Sicilian Gambit: reasons for maintaining the present antiarrhythmic drug classification. PMID- 1451135 TI - The Sicilian Gambit: a response to Drs Colatsky and Harrison. PMID- 1451136 TI - Effects of intravenous amiodarone on electrical dispersion in normal and ischaemic tissues and on arrhythmia inducibility: monophasic action potential studies. AB - OBJECTIVE: The aim was to study the effects of intravenous amiodarone on: (1) repolarisation and other monophasic action potential characteristics of normal and ischaemic tissues, and (2) vulnerability to pacing induced repetitive ventricular firing following acute left anterior descending coronary artery ligation. METHODS: Epicardial monophasic action potentials were continuously and simultaneously recorded from ischaemic and non-ischaemic regions of the hearts of 24 pentobarbitone anaesthetised dogs. Monophasic action potential duration, rise time, and amplitude, as well as the degree of dispersion of repolarisation between normal and ischaemic areas and vulnerability to electrical induction of repetitive ventricular firing, were determined using hand held silver-silver chloride "contact pressure" electrodes, before and 15 min after coronary ligation; and 15 min after exposure to low (10 mg.kg-1) doses of amiodarone. Similar determinations were made in drug free controls. RESULTS: Under control conditions, monophasic action potentials from both the (potentially) ischaemic and non-ischaemic regions were comparable, dispersion of repolarisation was minimal, and repetitive ventricular firing could not be induced. Coronary ligation significantly decreased monophasic action potential duration and increased rise time in the ischaemic, but not in the non-ischaemic, regions. Dispersion of repolarisation increased markedly. Repetitive ventricular firing could be induced in all dogs. "Low dose" amiodarone caused a much greater prolongation of repolarisation duration at ischaemic than at non-ischaemic sites. Dispersion of repolarisation decreased virtually to control levels and repetitive firing could no longer be induced in six of seven dogs. "High dose" amiodarone increased ischaemic region repolarisation duration and rise time relative to the non-ischaemic region to an even greater extent than the "low" dose, with the result that dispersion of repolarisation increased rather than decreased and repetitive ventricular firing again became inducible. CONCLUSIONS: The data indicate that: (1) intravenous amiodarone prolongs repolarisation of ischaemic tissues to a greater extent than that of normal tissues; (2) "low" dose amiodarone resulted in an overall decrease in dispersion of repolarisation, with little or no change in dispersion of rise time; (3) the "high" dose increased dispersion of both repolarisation and rise time. These changes were paralleled by changes in vulnerability to induction of repetitive ventricular firing by programmed ventricular pacing, the "low" dose being associated with decreases, and the "high" dose with further increases, in vulnerability, respectively. PMID- 1451137 TI - Left ventricular hypertrophy in a canine model of reversible pressure overload. AB - OBJECTIVE: The goal of therapy for left ventricular pressure overload should include regression of the associated left ventricular hypertrophy, but this process is incompletely understood. The aim of the study was to characterise the extent and time course of the progression and regression of pressure overload left ventricular hypertrophy in a canine hypertrophy model. METHODS: Six puppies were studied longitudinally with haemodynamic and echocardiographic measurements for 10 months. The study animals underwent ascending aortic banding at nine weeks of age which produced an initial gradient of 30 mm Hg. Subsequent growth led to an increase in gradient and the development of left ventricular hypertrophy. Then thoracotomy was again performed to remove the band. One month later, balloon aortoplasty was performed to remove the residual gradient. The animals were then observed for six months. RESULTS: Growth increased the gradient to 105(SEM 10) mm Hg three months after banding. The left ventricular weight to body weight ratio (g.kg-1), an index of hypertrophy, was 7.2(0.5) after three months of pressure overload. Subsequently the band was surgically removed, reducing the gradient to an average of 58(10) mm Hg. Balloon dilatation of the residual aortic stricture reduced the gradient further to 6(5) mm Hg. Over the ensuing six months, echocardiographic determination of left ventricular mass showed the regression in left ventricular hypertrophy. After six months, left ventricular weight to body weight ratio in the previously banded animals was significantly reduced from 7.2(0.5) to 5.3(0.2) (p less than 0.05). CONCLUSIONS: The model produced over 100% left ventricular hypertrophy, most of which regressed following removal of the pressure overload. PMID- 1451138 TI - Effects of chronic oral administration of nifedipine and diltiazem on occlusive thrombus of small coronary arteries in (NZW x BXSB)F1 male mice. AB - OBJECTIVE: (NZWxBXSB)F1 male mice were used as a model to study the effects of chronic administration of nifedipine and diltiazem on small coronary artery disease and mortality. METHODS: 16 week old (NZWxBXSB)F1 male mice were given either nifedipine (n = 29) at 20 mg.kg-1.d-1 orally or diltiazem (n = 28) at 100 mg.kg-1.d-1 orally in two divided doses until they were 24 weeks old (ie, for 60 d). Age matched control mice were given an equivalent volume of vehicle (n = 30). Mice that died received immediate necropsy. After 60 d, all surviving mice were killed and hearts and kidneys were examined histologically. RESULTS: The survival rate at 24 weeks was significantly higher in mice given nifedipine than in the controls (71% and 47%, respectively, p less than 0.05). The number of mice with myocardial necrosis, scar formation, or both, the percentage of areas of the ventricular wall with myocardial necrosis and scar formation, and the number of mice with small intramyocardial arteries showing greater than or equal to 75% stenosis were all significantly lower in the mice given nifedipine than in the controls. In the mice given diltiazem, there were no such differences from the controls. There was no evidence of significant stenosis or thrombosis in the extramyocardial coronary arteries in any of the mice. Systolic blood pressure and the rate-pressure product at 24 weeks of age, as well as the histological score for glomerulonephritis changes, were significantly lower in mice given nifedipine or diltiazem than in the controls. CONCLUSIONS: Despite an equivalent improvement of systolic blood pressure, the double product, and renal disease in nifedipine treated and diltiazem treated mice, only nifedipine prevented small coronary artery disease and increased the survival of (NZWxBXSB)F1 male mice, suggesting that nifedipine prevents occlusive thrombi of small coronary arteries better than diltiazem. PMID- 1451139 TI - Histochemical demonstration of endothelial superoxide and hydrogen peroxide generation in ischaemic and reoxygenated rat tissues. AB - OBJECTIVE: The aims were to test and evaluate two novel and independent histochemical methods for detecting the initial postischaemic burst of superoxide and hydrogen peroxide in buffer perfused rat tissues during reflow after 60 min warm ischaemia. METHODS: The first is a high manganese/diaminobenzidine technique, in which superoxide oxidises Mn2+ to Mn3+, which in turn oxidises diaminobenzidine to form amber coloured polymers, observable by light microscopy. The second is a high iron/diaminobenzidine technique, in which hydrogen peroxide oxidises diethylenetriaminepenta-acetate chelated Fe2+ to form intermediate species, which in turn oxidise diaminobenzidine similarly to Mn3+. Various isolated organs of the rat were rendered ischaemic for 60 min, and reperfused with oxygen or air equilibrated buffers containing diaminobenzidine and either Mn2+ or Fe2+. Tissues were fixed by perfusion with Trump's solution and processed for light microscopy. RESULTS: Both manganese and iron methods consistently showed the appearance of reaction product on the luminal surfaces of arterial, capillary, and venular endothelial cells in lung, heart, and intestine of the rat during the first 2 to 3 min of reoxygenation after ischaemia. The histochemical reactions were nearly absent in non-manganese-treated and non-iron-treated controls. Superoxide dismutase strongly inhibited Mn2+/diaminobenzidine reaction product formation and catalase strongly inhibited Fe2+/diaminobenzidine reaction product formation, when tested in specially perfused lung preparations in which these specific antioxidant enzymes were concentrated. CONCLUSIONS: These histochemical techniques provide direct, visual evidence that a burst of reactive oxygen species is generated in postischaemic rat tissues. The Mn2+/diaminobenzidine and Fe2+/diaminobenzidine techniques permit investigation of the endothelium derived reactive oxygen by simple laboratory procedures available to almost any investigator at low marginal cost. The endothelial oxidants so revealed may be of pathophysiological significance in a variety of cardiovascular disorders. PMID- 1451140 TI - Decreased collagen mRNA and regression of cardiac fibrosis in the ventricular myocardium of the tight skin mouse following thyroid hormone treatment. AB - OBJECTIVE: The aim was to study the effect of thyroid hormone on collagen gene expression in the myocardium of the tight skin mouse (TSK), a genetic model of myocardial fibrosis. METHODS: Heterozygous male (TSK/+) (n = 20) and normal (+/+) homozygous mice (n = 20), 1.5-2 months old of the C57 BL/6 strain were studied. Ventricular hypertrophy following thyroid hormone treatment (L-thyroxine, 10 micrograms.100 g-1 body weight daily intraperitoneally) was examined by measurement of the heart weight/body weight ratios and histological changes. Expression of fibrillar collagen types I and III in the ventricular myocardium was examined by measurement of the abundance of their respective mRNAs. Collagen synthesis was examined by measurement of hydroxyproline. Deposition of collagen types was evaluated by immunofluorescence staining. Expression of non-collagenous proteins, sarcomeric and cytoskeletal actin, was measured at the mRNA level. RESULTS: After 12 days of treatment ventricular hypertrophy was induced in the heart of the TSK mice. The results of northern hybridisation analyses showed that in the hearts of TSK mice 24 h after thyroxine treatment the abundance of mRNA for pro alpha 2 (I) collagen was decreased by 32% (p less than 0.05), pro alpha 1 (III) collagen by 47% (p less than 0.002), cytoskeletal actin by 50% (p less than 0.005), and sarcomeric actin mRNA by 34% (p less than 0.01) compared to the untreated TSK mice. The abundance of mRNA for pro alpha 2 (I) and pro alpha 1 (III) collagens in the thyroxine treated TSK mice were nearly comparable to that in normal homozygous mice. In TSK mice which were treated for 12 d, collagen content of the ventricular myocardium, as determined by hydroxyproline measurements, was decreased by 22.5% (p less than 0.01) compared to that in the heart of normal homozygous mice. CONCLUSIONS: Effects of thyroid hormone on ventricular gene expression in TSK mice result in a diminished collagen mRNA and collagen content and the disappearance of cardiac fibrosis. Thyroid hormone may selectively prevent the induction of cardiac fibrosis and play an important role in regression of cardiac fibrosis via endocrine pathways. PMID- 1451141 TI - Exogenous nitric oxide inhibits in vivo platelet adhesion following balloon angioplasty. AB - OBJECTIVES: The aim was to investigate the effects of an exogenous source of nitric oxide on in vivo platelet adhesion at the site of endothelial denudation after balloon angioplasty. METHODS: The study group consisted of 12 anaesthetised Large White pigs. Pigs were randomised to receive SIN-1 (3-morpholino sydnonimine), an exogenous donor of nitric oxide, or placebo before and during balloon induced vessel wall injury. Platelet deposition was quantified using the injection of autologous 111indium labelled platelets. Platelet function was also monitored by the measurement of bleeding time and ex vivo whole blood aggregometry. RESULTS: Superficial vessel wall injury was confirmed histologically and platelet monolayer formation was demonstrated by scanning electron microscopy. Platelet deposition at the site of endothelial denudation was markedly reduced following SIN-1 administration compared to placebo: 1.266(SEM 0.063) v 1.732(0.060) log platelets x 10(5).cm-2, p = 0.001. SIN-1 raised platelet cyclic GMP concentration, from 4.47(2.48) to 6.14(2.44) pg.platelet-1 (p less than 0.01) and prolonged the bleeding time, from 135(5) to 202(6) s (p = 0.001), but had non-significant effects on ex vivo whole blood aggregometry. CONCLUSIONS: Exogenous nitric oxide, through the activation of platelet soluble guanylate cyclase, inhibits platelet adhesion in vivo following balloon angioplasty. PMID- 1451142 TI - Fluorescence spectroscopy for identification of atherosclerotic tissue. AB - OBJECTIVE: Vessel perforation and limited steerability of the laser light are the major limitations of laser angioplasty. To improve steerability fluorescence spectroscopy has been proposed for identification of atherosclerotic plaques. The aim was to investigate this. METHODS: Fluorescence spectroscopy with three different excitation wavelengths (325 nm, 380 nm, 450 nm) was tested in an emission range of 400 nm to 600 nm. Intensity ratios at 480/420 nm were determined in different types of blood vessels. Necropsy material from 40 patients (punch biopsies of 4 mm diameter from the coronary and carotid artery as well as from the ascending and descending aorta) was studied spectroscopically. Histological alterations of the vessel wall were assessed by a semiquantitative score (0 to 10 points): (a) normal tissue, 0 to 2 points (mean = 0.25; n = 38); (b) mild atherosclerotic lesions, 3 to 5 points (mean = 3.35; n = 39); (c) severe atherosclerotic lesions, greater than or equal to 6 points (mean = 6.75; n = 43). RESULTS: Best spectroscopic results were obtained with an excitation wavelength of 325 nm. In samples with severe atherosclerotic lesions the fluorescence spectra showed a significant reduction of the emitted wavelength intensities when compared to normal tissue. There was a clear separation of the fluorescence spectra between normal and mild as well as between normal and severe atherosclerotic lesions; normal tissue showed an increased intensity in the range from 420 nm to 540 nm, whereas atherosclerotic lesions had no or only a small peak at 480 nm. There was a significant correlation between the semiquantitative score (n = 120) and the fluorescence ratio at 480/420 nm (excitation wavelength 325 nm) with a correlation coefficient of 0.87. The spectroscopic results showed no differences between the samples taken from different types of vessels. CONCLUSIONS: Fluorescence spectroscopy allows a reliable identification of normal and atherosclerotic lesions. The close correlation between the emitted light intensity ratio at 480/420 nm and the histological alterations of the vessel wall suggests a relationship between vessel wall fluorescence and the atherosclerotic alterations of the wall. PMID- 1451143 TI - Afterload dependent prolongation of left ventricular relaxation: importance of asynchrony. AB - OBJECTIVE: Acute increases in afterload and in left ventricular asynchrony both independently prolong left ventricular isovolumetric relaxation. The aim of the study was to investigate whether an increased left ventricular afterload augments left ventricular asynchrony, which in turn could mediate the afterload dependent prolongation of left ventricular isovolumetric relaxation. METHODS: Seven chloralose anaesthetised open chest dogs were instrumented with a left ventricular pressure gauge and two pairs of ultrasonic wall thickness crystals in the antero-apical and postero-basal left ventricular wall. At a constant heart rate of 149(SEM 7) beats.min-1, left ventricular pressure was acutely increased by brief manual clamping of the descending (AOCD) and ascending AOCA) thoracic aorta. Left ventricular asynchrony was quantified by the phase difference of the first Fourier harmonic between postero-basal and antero-apical wall motion. Global left ventricular relaxation was measured as the time constant of isovolumetric pressure fall, tau. Regional myocardial relaxation was assessed as the mean rate to half end diastolic thinning. RESULTS: AOCD increased left ventricular peak systolic pressure from 141.9(6.9) mm Hg to a maximum of 182.0(5.1) mm Hg and tau from 34.3(2.4) ms to 48.0(5.0) ms (p less than 0.05). Simultaneously, phase difference increased markedly during AOCD, from 12.7(3.5) degrees to 24.4(2.2) degrees (p less than 0.05). At matched left ventricular peak systolic pressures, AOCA increased tau from 33.4(2.5) ms to only 42.5(4.3) ms (p less than 0.05 v control and AOCD). Concomitantly, the increase in phase difference was smaller and statistically non-significant, at 13.7(2.9) degrees v 17.1(2.5) degrees. During 13 out of the 14 aortic clampings (7 AOCD, 6 AOCA), tau correlated linearly with phase difference [mean r = 0.74(0.03)]. In contrast to their effects on global left ventricular relaxation and asynchrony, neither AOCD nor AOCA influenced the rate to half end diastolic thinning. CONCLUSIONS: (1) left ventricular asynchrony may increase during an acute augmentation of left ventricular afterload; (2) this increased left ventricular asynchrony possibly contributes to the afterload dependent prolongation of left ventricular isovolumetric relaxation rate. PMID- 1451144 TI - Commentary on viewpoint article by A H Henderson, M J Lewis, A M Shah, and J A Smith (April, pages 305-8) PMID- 1451145 TI - Cardiac metabolism--emergence, decline, and resurgence. Part I. PMID- 1451146 TI - Ischaemic preconditioning: from mechanisms to exploitation. PMID- 1451147 TI - Mechanisms of ventricular arrhythmias in cardiac failure and hypertrophy. PMID- 1451148 TI - Variable effects of human and canine polymorphonuclear leucocytes on vascular smooth muscle tone. AB - OBJECTIVE: Previous studies have shown variable effects of human and canine polymorphonuclear leucocytes (neutrophils) on vascular tone. The aim of this study was to identify whether these variations in neutrophil function are due to species differences. METHODS: Canine and human arterial rings (with and without endothelium) were contracted with the thromboxane A2 analogue U46619, and then exposed to isolated neutrophils. RESULTS: Human neutrophils caused a significant relaxation of the human mammary arterial rings, and the relaxation was unaffected by the cyclo-oxygenase inhibitor indomethacin, enhanced by superoxide dismutase (SOD), and inhibited by oxyhaemoglobin. The relaxant effect of human neutrophils was also diminished upon pretreatment with NG-monomethyl-l-arginine (L-NMMA), indicating that the vasorelaxant material released by the neutrophils was nitric oxide (NO). Human neutrophils also relaxed canine femoral arterial rings, and the relaxant effect was potentiated by SOD and inhibited by pretreatment with oxyhaemoglobin or L-NMMA, confirming that the vasorelaxation was via release of NO. Canine neutrophils, on the other hand, caused an endothelium dependent contraction of autologous femoral arterial rings. This vasoconstriction was not affected by indomethacin, SOD, oxyhaemoglobin, or L-NMMA. However, treatment of canine neutrophils with the 5-lipoxygenase inhibitor piriprost attenuated (p < 0.02) their contractile effect on vascular rings, suggesting that neutrophil generated 5-lipoxygenase products were probably responsible for smooth muscle contraction. Presence of the leukotriene C4 and D4 receptor antagonist FPL 55,712 totally blocked the contractile effects of canine neutrophils, indicating that femoral arterial ring contraction was mediated by peptido-leukotrienes. CONCLUSIONS: The endothelium dependent nature of the canine neutrophil induced contraction suggests that the 5-lipoxygenase product leukotriene A4 is taken up by endothelial cells for conversion to peptido-leukotrienes. Since SOD had no effect and FPL 55,712 totally blocked the vasoconstrictor effects of canine neutrophils, it appears that the vasoconstrictor effects of the latter are mediated primarily through peptido-leukotrienes. In contrast, the vasorelaxation by human neutrophils is mediated through release of NO. PMID- 1451149 TI - Metabolic vasodilatation with glucose-insulin-potassium does not change the heterogeneous distribution of coronary blood flow in the dog. AB - OBJECTIVE: The heterogeneous distribution of coronary blood flow could represent regional differences in demand, or mismatching of regional O2 supply to demand, caused by regionally exhausted vasodilatation (anatomical/mechanical factors) or by regional arteriovenous diffusional O2 shunting. Regional coronary blood flow and global myocardial oxygenation and metabolism were measured during metabolic vasodilatation with glucose-insulin-potassium (GIK). METHODS: Variables were studied before and 30 and 60 min after start of a 30 min infusion of GIK (50% glucose, 4 ml.kg-1, 8 mM KCl, and 3 U insulin.kg-1). Regional blood flows were measured by radioactive microsphere technique and cardiac output by thermodilution. Experimental subjects were six anaesthetised mongrel dogs, weighing 20-27 kg. RESULTS: GIK increased plasma osmolarity and lactate, decreased haemoglobin, and increased cardiac output by 67(29)% and systemic O2 supply by 32(13)%, at unchanged arterial and central venous pressures and heart rate. Coronary blood flow rose by 97(50)% and left ventricular O2 supply by 56(41)%. Although regional blood flows in small tissue samples of about 1 g in the left ventricle ranged from a factor 0.31 to 1.73 of mean flow, GIK did not change flow heterogeneity and regional flows significantly correlated in time. Left ventricular O2 uptake rose by 42(40)%, while venous PO2 increased and O2 extraction decreased. Global lactate uptake increased at unchanged extraction. Changes were reversed after GIK. CONCLUSIONS: GIK transiently increases myocardial O2 uptake following a raised cardiac output, caused by a hyperosmolarity induced rise in cardiac contractility rather than by haemodilution. Although myocardial O2 supply is distributed heterogeneously, the fractional rise with GIK is almost equal among regions. At constant lactate extraction, increased venous PO2 and decreased O2 extraction do not indicate overperfusion in some regions at the cost of underperfusion in others, are probably caused by a small, direct vasodilating effect of hyperosmolarity, and argue against diffusional O2 shunting. As for global O2 supply to demand, the increase in regional O2 supply is probably well adapted to regionally increased demand during GIK, so that the heterogeneous distribution of O2 supply can be explained by regional differences in demand and not by regionally exhausted vasodilatation or O2 shunting. PMID- 1451150 TI - Echocardiographic determination of stroke volume during rapid atrial pacing and volume loading in normal rats. AB - OBJECTIVE: The aim was to validate echocardiographic assessment of acute changes of left ventricular stroke volume in normal rats. METHODS: By transthoracic use of a 7.5 MHz ultrasonic transducer, the left ventricular dimensions were determined before and during rapid atrial pacing and saline infusion in seven Wistar rats weighing 310-470 g. Left ventricular volume was calculated from short axis dimensions according to a cube function formula. Echo stroke volume (SVE) was then compared with that obtained simultaneously using a pulsed Doppler flow meter placed around the ascending aorta (SVF). RESULTS: The SVE (ml) was decreased from 0.30(SD 0.12) to 0.13(0.06) by rapid pacing and increased from 0.27(0.12) to 0.63(0.16) by volume loading. Regression analysis showed high correlations between SVE and SVF during both pacing (r = 0.84) and infusion (r = 0.91) studies. Furthermore, correlations between SVE and SVF in individual animals were very close (r = 0.87-0.99 in the pacing study and 0.92-0.99 in the volume study). Interobserver and intraobserver variances were small, with close correlations (r = 0.96-0.99) and modest standard errors of the estimate (0.02 0.04 ml) between the two measurements. CONCLUSIONS: Echocardiography allows reliable in vivo measurement of cavity dimensions and assessment of acute alterations in stroke volume in normal rats. PMID- 1451151 TI - Effects of exercise stress on left ventricular end diastolic pressure-length strain relations in dogs with and without coronary stenosis. AB - OBJECTIVE: The aim was to elucidate the alterations of left ventricular diastolic properties, taking into account changes in unstressed length during exercise stimuli with and without coronary stenosis. METHODS: Left ventricular end diastolic pressure-length strain relations using segment length normalised to Lagrangian strain, and the rate of relaxation, were studied in seven open chest anaesthetised dogs with and without coronary stenosis on both left anterior descending and circumflex coronary arteries (approximately 30% resting flow reduction) during simulated dynamic exercise. Regional segment length was measured with ultrasonic crystals placed in the left anterior descending subendocardial region, and unstressed segment length at zero transmural pressure was obtained by occluding the vena cava. RESULTS: Peak negative dP/dt was decreased and isovolumetric left ventricular relaxation time constant increased by coronary stenoses; however neither changed significantly during simulated exercise. Left ventricular end diastolic pressure was significantly increased by coronary stenoses, from 3.1(SEM 0.8) to 7.0 (0.9) mm Hg (p < 0.05), and further increased to 15.5(1.1) mm Hg (p < 0.01) during simulated exercise, although right ventricular end diastolic pressure did not change. Unstressed length was increased in coronary stenoses from 9.03(0.08) to 9.89(0.13) mm (p < 0.01), and further increased to 10.34(0.14) mm (p < 0.01) during exercise, whereas it tended to decrease without coronary stenosis, from 9.03(0.08) to 8.79(0.11) mm during exercise. Left ventricular end diastolic pressure-length strain relations progressively shifted upward and leftward with coronary stenoses and subsequent exercise, but shifted downward and rightward during exercise without coronary stenosis. CONCLUSIONS: The increase in unstressed length or volume may contribute to exercise induced left ventricular dilatation observed in patients in effort angina. End diastolic distensibility decreases in both mild supply induced and exercise induced ischaemia, whereas in the normal heart, left ventricular end diastolic distensibility increases during exercise. PMID- 1451152 TI - Mechanical restitution during alternans in guinea pig papillary muscles. AB - OBJECTIVE: The aim was to investigate alternate acceleration and retardation of mechanical restitution as a possible mechanism for mechanical alternans in isolated myocardium. METHODS: Mechanical alternans was induced in papillary muscles from the right ventricles of 11 guinea pigs (200-300 g) by rapid pacing under hypothermic conditions (T = 27 degrees C). Mechanical restitution curves were constructed by measuring the force responses to stimuli applied following variable test intervals during steady state pacing. Curves were obtained under control conditions (steady state stimulation interval 3 s), and for the beats following the large and small contractions during mechanical alternans. Monoexponentials were fitted to the restitution curves. RESULTS: The mean rate constant for restitution following the large beat in alternans was found to be slightly but significantly smaller than that following the small. Both rate constants obtained during alternans were significantly larger than the control rate constant (restitution was faster in alternans). In addition, as the alternation widened, the restitution curve of the beat following the small contraction developed a higher plateau than that following the large. CONCLUSIONS: The results confirm that the small beat in alternans is followed by faster restitution than the large. This alone is insufficient to explain the observed extent of alternans. The restitution curve for the beat following the small contraction must also rise to a higher plateau. Both the amount of calcium available for intracellular release and the rate at which it is made available vary from beat to beat. PMID- 1451153 TI - Haemodynamic and neurohumoral response in heart failure produced by rapid ventricular pacing. AB - OBJECTIVE: The aim was to determine the exact sequence of hormone changes during the progression of fluid retention in a canine model of "congestive cardiac failure" induced by rapid right ventricular pacing, and during recovery when pacing is stopped. METHODS: Rapid ventricular pacing at a rate of 250 pulses.min 1 was used in six mongrel dogs with implanted right ventricular pacemakers. Right heart haemodynamics were measured by means of Swan Ganz catheterisation, allowing flow measurement by thermodilution and pressure measurement by external manometry. Plasma renin activity, arginine vasopressin, and atrial natriuretic factor were assayed on venous blood samples by radioimmunoassay. Noradrenaline was assayed by high pressure liquid chromatography. RESULTS: The onset of rapid pacing was accompanied by a fall in cardiac output and a rise in pulmonary arterial, pulmonary capillary wedge, and right atrial pressures. Noradrenaline and atrial natriuretic factor rose. Plasma renin activity showed an initial fall followed by a rise, and arginine vasopressin was unchanged in the first 8 h. When rapid pacing was continued for a further 35 d, clinical signs of fluid retention appeared by day 28, by which time cardiac output had fallen, and central pressures risen further. Atrial natriuretic factor peaked at around 14 d whereas plasma renin activity, arginine vasopressin, and noradrenaline tended to reach a plateau at about d 20 and then to show further increases as clinical signs of fluid retention appeared; this was most marked with plasma renin activity. Cessation of pacing at d 35 caused a rapid reversal (increase) of cardiac output but a more gradual reversal (decrease) of right heart pressures over 5 d; only wedge pressure returned to base line. Arginine vasopressin and plasma renin activity fell rapidly to around 40% of the final pacing levels and reached basal values after 8 h and 48 h respectively. Noradrenaline fell after 8 h and reached basal levels in 5 d. Atrial natriuretic factor fell quickly by 60% after 8 h but remained above basal levels for 5 d. At the end of pacing, body weight fell rapidly in conjunction with a large diuresis. CONCLUSIONS: These findings are compatible with a major role of one or more of renin, vasopressin, and noradrenaline in the pathophysiology of the fluid retention of heart failure; the manifestations are not counteracted by the rise in atrial natriuretic factor. PMID- 1451154 TI - Myocardial oxygen requirements during experimental cardiopulmonary resuscitation. AB - OBJECTIVE: The aims were to determine myocardial oxygen requirements during cardiopulmonary resuscitation (CPR), and to test the hypothesis that endogenous catecholamines have a major effect on myocardial oxygen requirements in this setting. METHODS: Myocardial oxygen consumption (MVO2) was measured during 20 minutes of CPR in eight anaesthetised dogs. Coronary blood flow was maintained at prearrest levels using an external pump to provide a permissive level of oxygen delivery during ventricular fibrillation. Oxygen content was measured in arterial and coronary sinus blood samples under prearrest conditions and at 5 min intervals during CPR. Four dogs were given propranolol (1 mg.kg-1) following the 5 min measurements. RESULTS: MVO2 averaged 108.7(SEM 12.8)% of the initial prearrest values after 5 min CPR (n = 8). After 10 min CPR, MVO2 fell to 53.8(13.3)% of the initial prearrest values in the subset of animals given propranolol after the 5 min measurements (n = 4), but remained at prearrest levels in untreated animals (p < 0.05 for an interactive effect between treatment and time). MVO2 subsequently tended to decrease with time in untreated animals, but remained a high percentage of prearrest values throughout the 20 min period of CPR. CONCLUSIONS: These findings suggest that endogenous sympathetic stimulation of the fibrillating heart results in high myocardial oxygen requirements during CPR. PMID- 1451155 TI - Effect of 5-aminosalicylic acid on myocardial capillary permeability following ischaemia and reperfusion. AB - OBJECTIVE: The aim was to evaluate the effect of 5-aminosalicylic acid on myocardial capillary permeability for small hydrophilic molecules after ischaemia and reperfusion. METHODS: Open chest anaesthetised dogs were subjected to a 20 min occlusion of the left anterior descending coronary artery followed by 1 h reperfusion. 5-Aminosalicylic acid (bolus injection 12 mg.kg-1, followed by 105 micrograms.kg-1.min-1) (n = 10) or saline (control, n = 12) was given intravenously for 1 h, starting 20 min before ischaemia. The myocardial plasma flow rate, myocardial capillary extraction fraction, and myocardial capillary permeability-surface area (PS) product for 99mTc-DTPA were determined before ischaemia, and 5 and 60 min after the start of reperfusion by employing the single injection residue detection method. Immediately after reperfusion, the reactive hyperaemic plasma flow was measured by the 133Xe washout method. RESULTS: Four dogs (two untreated and two treated with 5-aminosalicylic acid) were eliminated due to ventricular fibrillation at the time of reperfusion. In the remaining animals (10 controls and eight treated) the plasma flow rate, capillary extraction fraction and PS were similar before myocardial ischaemia. After 5 min reperfusion, the plasma flow rate and PS were significantly increased in control animals (p < 0.02 and p < 0.008, respectively), but were unchanged in dogs treated with 5-aminosalicylic acid. In addition, after 5 min reperfusion, PS was significantly higher in the control group than in treated animals (p < 0.005). Microcirculatory variables returned to preocclusive values in both groups by 60 min after reperfusion. 5-Aminosalicylic acid had no significant effect on haemodynamics or on reactive hyperaemic plasma flow. CONCLUSIONS: The results suggest that 5-aminosalicylic acid can attenuate the microvascular changes after reversible myocardial ischaemia. The effect is potentially beneficial, and may be mediated by well recognised anti-inflammatory actions of 5-aminosalicylic acid (ie, scavenging of oxygen free radicals and neutrophil inhibition). PMID- 1451156 TI - Imipramine induced heart failure in the dog: a model to study the effect of cardiac assist devices. AB - OBJECTIVE: The value of intravenous imipramine in creating a reversible model of short term heart failure was evaluated in anaesthetised dogs. METHODS: Acute effects of imipramine were studied in 11 dogs using invasive haemodynamic pressure measurements and two dimensional echo evaluation. RESULTS: After a 30 min imipramine infusion (7.5 mg.kg-1.h-1), positive left ventricular dP/dtmax decreased from 1368(SEM 108) to 909(119) mm Hg.s-1 (p < 0.05), left ventricular end diastolic pressure increased from 8(1) to 12(2) mm Hg (p < 0.05), while left ventricular pressure decreased from 106(4) to 87(6) mm Hg (p < 0.05). Cessation of imipramine administration resulted within 60 min in partial restoration of cardiac function. This deterioration and subsequent recovery was also demonstrated with echocardiographic measurements, which showed a decrease in ejection fraction from 54(3)% to 28(2)% (p < 0.05). During administration of imipramine neither significant electrophysiological changes nor supraventricular/ventricular arrhythmias were seen. Repeated infusions of imipramine in three anaesthetised dogs with a two week interval showed the reproducibility of the haemodynamic effects and the recovery of ventricular function. Since the model was developed to evaluate the use of cardiomyoplasty in heart failure, the effect of imipramine was also evaluated on latissimus dorsi muscle contraction. Administration of imipramine did not affect skeletal muscle force development at the dosage used to create heart failure. CONCLUSIONS: This model can be used to produce short term reversible heart failure in anaesthetised animals to test the efficacy of supportive interventions like dynamic cardiomyoplasty, intra-aortic balloon pumping, and mechanical cardiac assist devices. PMID- 1451157 TI - Adenosine induced chest pain--a comparison between intracoronary bolus injection and steady state infusion. AB - OBJECTIVE: Adenosine may induce chest pain in at least two ways, either by direct stimulation of sensory afferents before actual ischaemia occurs or secondary to ischaemia. The aim was to study if the mechanism of pain induction may depend on the method of adenosine administration. METHODS: Increasing doses of adenosine were given to seven male patients with ischaemic heart disease referred for coronary angiography: first as a bolus intracoronary injection (2.5-50 mumol), second as a 1 ml.min-1 steady state infusion (0.01-20 mumol.min-1) and third as an intravenous steady state infusion (0.076-0.76 mumol.kg-1 x min-1). Pain, rate pressure product, coronary sinus blood flow, and ECG were monitored. Lactate was analysed in coronary sinus and arterial blood. RESULTS: After intracoronary bolus injection there were no signs of myocardial ischaemia, whereas during intracoronary steady state infusion, and in spite of a lower, but definite, degree of pain, 5/7 patients showed myocardial lactate production and three patients showed ST depression. During the intravenous steady state infusion 6/6 patients showed ST depression. CONCLUSIONS: These findings suggest that when using adenosine for studies on the mechanisms of chest pain in patients with ischaemic heart disease it is preferable to use an intracoronary bolus injection technique rather than a steady state infusion, as the risk of inducing ischaemia with the latter model cannot be ignored. PMID- 1451158 TI - Cardiac metabolism--emergence, decline, and resurgence. Part II. PMID- 1451159 TI - Onset of acute myocardial infarction--circadian variation and triggers. PMID- 1451160 TI - Pulmonary artery compliance: its role in right ventricular-arterial coupling. AB - OBJECTIVE: The aim was to investigate the ventricular/vascular coupling of the intact right heart under conditions of normal operation and acute pulmonary hypertension. METHODS: Right ventricular contractility was obtained by calculating the end systolic pressure-volume relationship (Ees) and the effective pulmonary arterial elastance (Ea), applying the Windkessel parameters of the pulmonary arterial input impedance. Coupling between the ventricle and its load could be determined in terms of Ees and Ea. Acute pulmonary hypertension was induced by injecting glass microspheres into the pulmonary vascular bed until a mean pulmonary arterial pressure of more than 35 mm Hg had been reached. Experimental subjects were Landras/Large white pigs (n = 11), studied under general anaesthesia. Ees was obtained by normalising the right ventricle pressure diameter equivalent of Ees to stroke volume. The lumped element parameters of the Windkessel analogue were calculated from the pulmonary artery pressure and blood flow. Stroke work was calculated from the pressure-volume loop and oxygen consumption derived from the pressure-volume area. Efficiency was taken to be the ratio between stroke work and oxygen consumption. RESULTS: Ea increased significantly as mean pulmonary artery pressure rose, while Ees remained linear and constant. Stroke work, as well as efficiency, increased, with the maximum of the stroke work curve lying to the right of the efficiency maximum. At the control step (before pulmonary artery hypertension), Ees = 1.71 Ea (n = 11). CONCLUSIONS: Under control conditions, the right ventricle operates at maximum efficiency and submaximal work output. Compliance of the pulmonary artery is a significant factor in decoupling the right ventricle from its vascular load. As the compliance decreases with acute pulmonary hypertension, the maximum stroke work against load point shifted in such a manner that the right ventricle changed its operational status from a flow to a pressure pump, resulting in a decreased stroke volume. PMID- 1451161 TI - Functional changes in the right and left ventricle during development of cardiac hypertrophy and after its regression. AB - OBJECTIVE: The aim was to determine left and right ventricular functional reserves and collagen concentration during the development of cardiac hypertrophy and after its regression. METHODS: Two experimental models of cardiac hypertrophy (chronic thyroxine or isoprenaline treatment of adult rats) were compared 24 h and five weeks after the agent was last given. Pressure changes in the left (right) ventricle before and after acute aortic (pulmonary artery) ligation were recorded in open chest anaesthetised animals. The difference in dP/dtmax after and before ligation was regarded as the functional reserve. The total collagen concentration was determined in both ventricles separately by means of hydroxyproline. RESULTS: Left and right ventricular weight increased by 20% and 30% respectively in the two models employed. In the thyroxine treated group, the functional reserve of the left ventricle rose very noticeably, whereas in the isoprenaline treated group it decreased. The right ventricular functional reserve did not differ from that in the controls in either of the two groups. The collagen concentration rose in the left ventricle in the isoprenaline group only. Five weeks after the last administration of the agent, cardiac mass and ventricular function did not differ from the control values in either of the models studied; the only exception was the incomplete regression of left ventricular hypertrophy and persistent structural and functional impairment of the left ventricle in the isoprenaline treated group. CONCLUSIONS: Our results indicate that hearts undergoing a comparable degree of experimental hypertrophy may have different functional and structural properties; significant differences were found between the right and left ventricular response. Regression of hypertrophy together with a reversal of ventricular function usually occurs unless the myocardium has received severe structural damage. PMID- 1451162 TI - Effects of adenosine on cardiac performance and phosphate compounds in microembolised guinea pig hearts. AB - OBJECTIVE: The excessive release of adenosine has been reported to cause hyperaemia and to attenuate ischaemic injury in microembolised hearts. The direct effects of exogenous adenosine on cardiac performance were investigated in microembolised guinea pig hearts with the simultaneous measurement of phosphate compounds. METHODS: 21 male guinea pig hearts were perfused according to the Langendorff technique and microembolism was induced by injecting microspheres. Hearts were then treated as follows: group A, adenosine 20 microM and theophylline 60 microM; group B, theophylline 60 microM; group C, saline (control). Cardiac performance was monitored and phosphate compounds were measured by 31P magnetic resonance spectroscopy. RESULTS: Group A showed a significant increase in the left ventricular developed pressure and coronary flow, and a modest restoration of ATP content. Pi/(Pi+Pcr) remained virtually constant. There were no significant changes in left ventricular developed pressure or coronary flow in groups B and C. There was a gradual decrease in tissue ATP content and slight increase in Pi/(Pi+Pcr). CONCLUSIONS: Adenosine improved cardiac performance without adverse effect on energy metabolism in microembolised hearts. Adenosine also restored the ATP stores in microembolised hearts. (Pi = inorganic phosphate; Pcr = phosphocreatine.) PMID- 1451163 TI - Myocardial stretch alters twitch characteristics and Ca2+ loading of sarcoplasmic reticulum in rat ventricular muscle. AB - OBJECTIVE: The aim was to determine the influence of diastolic muscle length on force development and timing parameters of cardiac muscle twitch contraction and to determine whether a length dependency exists for the calcium loading capacity of the sarcoplasmic reticulum. METHODS: Right ventricular papillary muscles and trabeculae were isolated from hearts of female Wistar rats weighing 220-280 g. Papillary muscles were stretched to diastolic lengths of 90, 95, and 100% Lmax and paced at 1.0 Hz. Individual twitch profiles were characterised by their peak force and the maximum rate (dF/dt) of the positive and negative force changes. Intrinsic timing was identified through waveform analysis that divided the twitch profile into time domains for the ascending limb (T0-T1; T1-T2) and the descending limb (T2-T3; T3-T4). Each domain was compared at three muscle lengths. The sarcoplasmic reticular calcium content at short (1.88 microns) and long (2.11 microns) sarcomere lengths was characterised by rapid cooling contractures after 1 s and 60 s of diastolic rest. RESULTS: Peak developed force and the maximum rate of positive and negative force development decreased as diastolic muscle length was reduced from Lmax to 90% Lmax. The intrinsic timing for the segment that reflects the relaxation phase of the twitch (T1-T4) was shortened as muscle length was reduced. The time domain that reflects the combined effects of calcium release and the early phase of contraction (T0-T1) was insensitive to diastolic muscle length. The fractional release of sarcoplasmic reticular calcium at different muscle lengths was approximately 32-35% of the total sarcoplasmic reticulum calcium pool. CONCLUSIONS: The data on the intrinsic timing of the twitch characteristics coupled with rapid cooling contracture analysis suggests a fractional calcium release that is approximately 32-35% of the total sarcoplasmic reticular capacity at either long or short muscle lengths. However, the loading capacity of the sarcoplasmic reticulum is greater when the muscle operates at a shorter diastolic length. This can be interpreted as meaning that diastolic muscle length differentially influences sarcoplasmic reticular calcium storage and release processes. PMID- 1451164 TI - Dietary fat modulation of left ventricular ejection fraction in the marmoset due to enhanced filling. AB - OBJECTIVE: The aim was to investigate the influence of long term dietary fish oil consumption on cardiac function in a non-human primate, to elucidate further the basis of the apparently reduced cardiovascular disease mortality associated with its consumption in man. METHODS: Adult male marmoset monkeys (Callithrix jacchus) were fed diets supplemented with polyunsaturated fatty acids (PUFA) of marine (tuna fish oil) or plant (sunflower seed oil) origin, saturated animal fat (sheep perirenal fat), or a low fat reference diet for 24 months. Cardiac function was assessed using radionuclide angiography under pentobarbitone anaesthesia with a counts based adaptation for ventricular volume estimations. Measures were made at rest and during infusion of adrenaline. RESULTS: The mean left ventricular ejection fraction was greater in the tuna fish oil group [55.0(SEM 1.1)% n = 7] and the sunflower seed oil group [58.1(2.4)% n = 8] than in the reference group [48.5(1.4)% n = 9] and the sheep fat group [47.6(1.8)% n = 8]. This was associated with a more than 25% greater end diastolic volume and 40-70% increases in stroke volume in tuna fish or sunflower seed oil fed animals. There was no evidence of cardiac hypertrophy. In contrast, adrenaline increased stroke volume and ejection fraction by increasing emptying, thus reducing residual end systolic. Tuna fish oil fed animals had a low resting heart rate. When this was raised to comparable levels by adrenaline, lower pressure-rate indices and greater cardiac minute work suggested higher myocardial energy efficiency in PUFA fed animals compared with the reference and sheep fat groups. CONCLUSIONS: Dietary fish oil and sunflower seed oil increased the left ventricular ejection fraction in the marmoset monkey by enhancing ventricular filling, thus providing an energy sparing promotion of diastolic relaxation. PMID- 1451165 TI - Mechanical determinants of myocardial oxygen consumption with special reference to external work and efficiency. AB - OBJECTIVE: The aim of the study was to investigate the ambiguous effect of left ventricular afterload on myocardial work, oxygen consumption, and efficiency. METHODS: Myocardial oxygen consumption and mechanical parameters of the left and right ventricle were measured in situ in a modified heart-lung preparation in the rat. Left ventricular afterload was adjusted arbitrarily by means of a Starling resistor mounted in a shunt circuit between the left ventricle and the caudal caval vein. Left and right ventricular pressure and aortic pressure as well as pulmonary flow and the flow in the shunt circuit were measured. The left ventricular pressure and volume values were converted into wall stress and length data assuming a thick walled sphere, and external work was calculated from left ventricular force and shortening. RESULTS: Left ventricular external work ran through a maximum with decreasing aortic pressure. Left ventricular oxygen consumption per gram and beat correlated linearly with left ventricular peak wall stress, tension-time integral, and maximum rate of stress development. Left ventricular force and shortening, the two components of external work, acted differently: force determined left ventricular oxygen consumption, whereas shortening had no direct effect on myocardial oxygen consumption, but was important in determining left ventricular efficiency. CONCLUSIONS: The interplay between left ventricular afterload and coronary perfusion pressure is of special significance for the heart in situ. The decrease in shortening and external work as well as the diminution in efficiency, observed at low aortic pressure values, can be attributed to impaired coronary perfusion. The coronary perfusion pressure must therefore be taken into consideration for the critical examination of the efficiency of the heart in situ. PMID- 1451166 TI - Failure of mannitol to reduce myocardial infarct size in the baboon. AB - OBJECTIVE: The aim was to determine whether mannitol, previously shown to have several myocardial protective properties, could reduce the myocardial infarct size after coronary occlusion in the baboon. METHODS: Anaesthetised baboons underwent a 2 h transient coronary artery occlusion. Each was randomised into one of two groups receiving either mannitol (n = 6) or no adjunct (n = 8). Mannitol (20%) was given at a rate of 0.4 ml.min-1 x kg-1 starting at 105 min postocclusion until reperfusion was allowed at 2 h, and at a rate of 0.2 ml.min-1 x kg-1 thereafter, until a total of 500 ml had been delivered. Changes in the ST segments were recorded with epicardial wires. The animals were killed at 24 h postocclusion and the hearts excised. Silicone microvascular dye was injected into the previously occluded coronary artery to delineate the perfusion bed. The hearts were fixed in formalin, sliced, and mounted on slides. Using planimetry the ratios of the mean volume of infarct to the mean volume of the perfusion bed (VI/VPB) were calculated and compared. RESULTS: The VI/VPB for the mannitol treated group was 71.7(SEM 14.0)% and for the control group, 65.6(6.9)% (NS). No significant difference was noted in the mean summated ST segment elevations between the two groups. CONCLUSIONS: Mannitol does not reduce myocardial infarct size or ischaemia in the baboon. PMID- 1451167 TI - Interdependence of intracellular taurine and sodium in guinea pig heart. AB - OBJECTIVE: The aim was to investigate the effects of raising intracellular taurine on the intracellular sodium activity (aNa1) in isolated guinea pig ventricular myocytes, and the effect of procedures that raise intracellular sodium on taurine concentration in the perfused guinea pig ventricular tissue. METHODS: Taurine was introduced into the sarcoplasm of isolated ventricular myocytes, either during cell isolation or by diffusion from a penetrating micropipette, and the effect on aNai was measured using an ion sensitive microelectrode. Guinea pig hearts, mounted on a Langendorff apparatus, were perfused with a variety of physiological media and the level of taurine in the ventricles determined using high pressure liquid chromatography. RESULTS: An increase in intracellular taurine caused by its presence during cell isolation or by diffusion from a micropipette significantly reduced the aNai of isolated myocytes at rest, during perfusion with Ca depleted solutions, or on inhibition of the Na pump. In the guinea pig ventricles, taurine at 13.0(SEM 0.6) mmol.kg-1 wet weight comprised up to 45% of the free amino acids; since plasma taurine was 64(13) mumol.litre-1, this means that in vivo a large outwardly directed gradient for taurine exists (equivalent to a free energy of 13.7 KJ.mol-1). Upon perfusion with Ca,Mg free Tyrode solution (which raises intracellular sodium markedly), a time dependent loss of taurine occurred. Both the rate of loss and the total amount lost were increased when the Na pump was also inhibited. This loss of tissue taurine was not due to release from dead or lysed cells, as it was antagonised by procedures known to reduce the rise of aNai during Ca depletion, was inhibited by beta alanine (an inhibitor of taurine transport), and the fall in tissue taurine was not correlated with the appearance of lactate dehydrogenase in the effluent. CONCLUSIONS: The data from isolated myocytes and perfused guinea pig hearts were consistent with the presence of a Na/taurine symport which is activated to cause efflux of Na and taurine when either rise above their physiological level. PMID- 1451168 TI - Digoxin and digoxin derivative induced arrhythmias: in vitro binding and in vivo abolition of arrhythmias by digoxin immune Fab (DIGIBAND). AB - OBJECTIVE: The aim was to compare the binding characteristics of a highly purified digoxin specific antigen binding fragment (digoxin immune Fab: DIGIBIND) with digoxin and with two commonly used derivatives of digoxin, beta methyl digoxin and beta acetyl digoxin, and to assess its ability to abolish the arrhythmogenic effects of these digitalis glycosides. METHODS: The binding characteristics of DIGIBIND with digoxin, beta methyl digoxin, and beta acetyl digoxin were assessed in vitro by measuring their ability to inhibit the binding of DIGIBIND to 3H-digoxin. From these studies the affinities of the interactions between DIGIBIND and these glycosides, and the binding capacity of DIGIBIND for each of these glycosides, could be measured. The ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin, beta methyl digoxin, and beta acetyl digoxin was assessed using an in vivo anaesthetised guinea pig model (n = 36, weight 300-400 g), in which these glycosides were infused intravenously (50 micrograms.kg-1 x min-1) until the onset of ventricular arrhythmias, at which point the total amount of glycoside given was calculated. A single bolus dose of either vehicle or DIGIBIND was then given intravenously, and the time to restoration of normal cardiac rhythm noted. After the administration of DIGIBIND, a second infusion of the same glycoside was given to reinitiate the ventricular arrhythmias. The time to onset of the arrhythmias was noted, and the additional amount of glycoside given calculated. RESULTS: In vitro studies showed the binding of DIGIBIND to 3H-digoxin to be inhibited by digoxin and by the two derivatives. The affinities of these interactions with DIGIBIND were significantly different, that for digoxin being some twofold greater than that for beta methyl digoxin and beta acetyl digoxin. The ED50 concentrations were 14.1 (95% CI 12.2, 15.2), 29.2(26.1, 32.7), and 36.2(33.0, 39.8) nM, respectively. However, there were no significant differences between these glycosides in their binding capacities. The in vivo studies showed that intravenous infusion of digoxin, beta methyl digoxin, or beta acetyl digoxin induced similar ventricular arrhythmias. The onset of the arrhythmias was clearly discernible, and required a significantly lower dose of digoxin compared with that of beta methyl digoxin and beta acetyl digoxin. These doses were 667(SEM 55), 868(33), and 854(40) nmol.kg-1, respectively. Termination of the infusion had no effect on the arrhythmias, and in those animals which received a bolus intravenous injection of saline there was no return to normal cardiac rhythm. By contrast, in animals which received a bolus intravenous injection of DIGIBIND, there was complete abolition of the arrhythmias within 4-6 min. Although the dose of DIGIBIND given to abolish digoxin induced arrhythmias was approximately 25% less than that given to abolish beta methyl digoxin and beta acetyl digoxin induced arrhythmias (p < 0.05), the time to restoration of normal cardiac rhythm after DIGIBIND was not significantly different for digoxin compared with beta methyl digoxin and beta acetyl digoxin, at 4.6(0.9), 4.9(0.8), and 5.7(0.8) min, respectively. To reinitiate the arrhythmias in those animals which had received DIGIBIND, a dose of glycoside was required which was not significantly different from that given prior to the DIGIBIND. This observation therefore confirmed the stoichiometric relationship between DIGIBIND and each of the glycosides in respect of the neutralising action of DIGIBIND in abolishing the arrhythmogenic effects of these agents. CONCLUSIONS: Although there is some small difference in the affinities of the binding interactions, there is no difference in the binding capacities of DIGIBIND for digoxin, beta methyl digoxin, or beta acetyl digoxin in vitro. These binding interactions are manifest as the ability of DIGIBIND to abolish the arrhythmogenic effects of digoxin and the two derivatives in vivo. PMID- 1451169 TI - Anatomical identification of glomeruli in the antennal lobes of the male sphinx moth Manduca sexta. AB - Computer-assisted neuroanatomical methods have been used to demonstrate unique identities of the glomeruli of the antennal lobes (ALs) in males of the sphinx moth Manduca sexta. The glomerular neuropil consists of the male-specific macroglomerular complex, which comprises two closely apposed bulky subunits, and 64 +/- 1 "ordinary" glomeruli arrayed in a shell around a central region of coarse neuropil. Computer-generated maps show the exact locations of all glomeruli and adjacent groups of neuronal somata in a constant Cartesian coordinate system, such that these can be accurately identified in any individual. The glomeruli belong to three classes according to the number and type of identification criteria they satisfy. The larger class comprises glomeruli (n = 44) identified only in the computer-generated maps on the basis of their relative positions. The other two classes include glomeruli that were also identified in sections, either directly from their proximity to readily identifiable structures and their shape and size (n = 10, including the labial palp-pit-organ (LPO) glomerulus), or indirectly from their positions relative to the former (n = 9). Two very small glomeruli were present in only one AL, demonstrating the existence of anomalous glomeruli, whereas another glomerulus had no homologue in both ALs of one individual. The true number of ordinary glomeruli (per male AL) was thus estimated to be 64. The uncertainty in delineating some glomeruli might affect this number without implying modification of the homologies proposed. The locations of tracts and cell groups, both within and near the AL, are also invariant with respect to glomeruli, as shown in the computer maps. The methods employed are general and might be useful to researchers in related fields. The results obtained call for more attention to the precise geometry of neural structures. PMID- 1451170 TI - Distribution of laminin, type IV collagen, and fibronectin in the cell columns and trophoblastic shell of early macaque placentas. AB - The cytotrophoblastic cell columns and trophoblastic shell of macaque placentas accumulate progressively greater amounts of intercellular material during early gestation. We studied the composition of this material in placentas collected from 22-34 days of gestation by using immunoperoxidase techniques directed to the extracellular matrix molecules fibronectin, type IV collagen, and laminin. These antigens co-localized within the intercellular deposits at all stages studied. At day 22 the proximal cell columns were composed of cells with narrow interstices and which lacked immunoreactivity for the 3 antigens. Distally the cells were vacuolated and the intercellular spaces increased in size and contained dense matrix deposits. The trophoblastic shell consisted of closely packed, non vacuolated cytotrophoblast cells with only a delicate meshwork of matrix. By day 27 the matrix deposits of the distal cell columns increased markedly in size. The trophoblastic shell contained larger numbers of vacuolated cells and was occupied by accumulations of matrix. By 34 days the matrix deposits of the cell columns expanded substantially along the longitudinal axes of the columns. These deposits were often continuous with a matrix-dense, cell-deficient layer in the trophoblastic shell. This matrix-rich zone lay between a cellular layer adjacent to the intervillous space and a similar, but discontinuous, cell layer that formed the junctional zone with the endometrium. PMID- 1451171 TI - Localization of xenopsin and xenopsin precursor fragment immunoreactivities in the skin and gastrointestinal tract of Xenopus laevis. AB - Xenopsin (Xp) and xenopsin precursor fragment (XPF) are bioactive peptides derived from a single precursor molecule; both were isolated previously from extracts of Xenopus laevis skin. The present immunohistochemical study was undertaken to determine the specific cellular localization of these two peptides in the skin and also in the gastrointestinal tract of adult Xenopus. We report here that Xp-like and XPF-like immunoreactivities co-exist in the granular glands of the skin and specific granular cells in the lower esophagus and stomach. However, only Xp-like immunoreactivity, not XPF-like immunoreactivity, was detected in tall, thin cells of the duodenum and in club-shaped cells of the large intestine. The immunochemical co-localization of the two peptides in specific cells of the skin, lower esophagus and stomach suggests that the same gene is expressed in each of these cells, and that the precursor molecule undergoes similar post-translational processing. In contrast, the observation that certain cells of the duodenum and large intestine display only one peptide immunoreactivity suggests an alternative phenomenon, possibly involving selective peptide accumulation or expression of a different gene. PMID- 1451172 TI - Characterization of macrophage-like cells in the external layers of human small and large intestine. AB - In the external layers of human small and large intestine macrophage-like cells were characterized by immunohistochemical, histochemical and electron microscopical methods. Using immunohistochemistry and a number of monoclonal antibodies, the presence and distribution of phenotypic subpopulations of macrophages were evaluated. In all locations macrophage-like cells were identified with antibody EBM11, which recognizes CD68 antigen, C3bi which recognizes CD11b, and partly with an antibody which recognizes protein 150,95 (CD11c). Macrophage-like cells in the external muscle layer were HLA-DR-positive (expressing the MHC class-II antigen), in contrast to macrophage-like cells in the subserosa and submucosa. Macrophage-like cells in the external muscle layer were mostly acid phosphatase-negative, and at the electron-microscopic level they were found to have features of macrophages: primary lysosomes, coated vesicles and pits. However, very few secondary lysosomes were present. Birbeck granules were not observed. It is concluded that in the external muscle layer of human small and large intestine numerous macrophages of a special type are present. It is discussed whether this cell type plays a role in gastrointestinal motility and/or has an immunological function. PMID- 1451173 TI - Postsmolt change in numbers of acetylcholinesterase-positive cells in the pineal organ of the Pacific coho salmon. AB - We have examined the occurrence of acetylcholinesterase (AChE)-positive cells in the pineal organ of different developmental stages of the Pacific coho salmon. Large numbers of AChE cells were present in freshwater living alevins, in all stages of presmolts (n = 307-544), and in adult spawners (n = 696-1774), whereas seawater-living postmolts displayed a total lack of labeled cells. The AChE reactive cells were evenly distributed within the pineal end-vesicle and stalk of the presmolts and adults. However, the AChE-positive cells that occurred in the pineal stalk were of a smaller type and more uniform in shape than the cells of the pineal end-vesicle. The dense populations of AChE-stained cells in the alevins were all situated in the caudal part of the pineal end-vesicle. We conclude that changes in pineal metabolism occur in postsmolt salmon that live in salt-water. It is not clear whether the observed change in pineal AChE expression is an "unspecific" change caused by the life in the sea, reflecting alterations that are related to aspects of osmoregulation, and/or is involved in the visual function of the pineal organ resulting from changes in the environmental lighting conditions, e.g., photoperiod, light-intensity, or spectral composition. This study adds to our previous findings of changes that occur in the central nervous system of the salmon during the time of the parr-smolt transformation and migration between limnic and marine environments, and indicates a possible central role of the pineal organ in the control of these events. PMID- 1451174 TI - Peptidergic neurons of the crab, Cardisoma carnifex, in defined culture maintain characteristic morphologies under a variety of conditions. AB - Peptidergic neurons dissociated from the neurosecretory cell group, the X-organ, of adult crabs (Cardisoma carnifex) show immediate outgrowth on unconditioned plastic dishes in defined medium. Most of the neurons can be categorized as small cells, branchers or veilers. A fourth type, "superlarge," found occasionally, has a soma diameter greater than 40 microns and multipolar outgrowth. We report here the effects on morphology that follow alterations of the standard defined culturing conditions. The three common types of neurons are present when cells are grown in crab saline or saline with L-glutamine and glucose (saline medium). Changes of pH between 7.0 to 7.9 have no effect. Osmolarity changes cause transient varicosities in small cells. In some veilers, pits rapidly appear in the veil and then disappear within 35 min. In cultures at 26 degrees C instead of 22 degrees C, veilers extend processes from the initial veil in a pattern similar to branchers, and the processes of adjacent veilers sometimes form appositions. Culturing in higher [K+]o medium ([K+]o = 15-110 mM; standard = 11 mM) has no long-term effect, but growth is arrested by [K+]o greater than 30 mM. Cultures were also grown in media in which [Ca2+]o ranged from 0.1 microM to 26 mM (standard = 13 mM). Outgrowth occurred from all neuronal types in all [Ca2+]o tested. Thus, the expression of different outgrowth morphologies occurs under a wide variety of culturing conditions. PMID- 1451175 TI - Embryonic chicken gizzard: immunolocalization of collagen and smooth muscle myosin. AB - Antibodies to chicken gizzard myosin and to chicken skin collagen type I allow the myofibrillar and connective tissue development in the embryonic chicken gizzard to be followed. Fibroblasts are assumed to synthesize collagen prior to the onset of smooth muscle cell development in the muscle primordium (day 5); they are presumably also responsible for collagen synthesis close to the presumptive lamina propria and in the developing tubular glands (day 14 to 17). From day 6 to 8, myosin and collagen are colocalized intracellularly, and from day 9 onward collagen fibers start to appear extracellularly, eventually forming the trellis-like connective tissue septa that give the rhomboid profile found in the adult muscle. The close association of collagen and myosin in early development suggests that the muscle cells themselves produce and export collagen. PMID- 1451176 TI - Gonadotropin-releasing hormone neurons and pathways in the brain of the female mink (Mustela vison). AB - The distribution of gonadotropin-releasing hormone-immunoreactive neurons and processes was mapped in the female mink brain using coronal, horizontal and sagittal sections. Perikarya were found along a ventral continuum including the olfactory tubercle, the diagonal band of Broca, the lateral septum, the preoptic and anterior hypothalamic area and the mediobasal hypothalamus; 80% of the perikarya were counted in the mediobasal hypothalamus. Fibres were mainly observed in the organum vasculosum of the lamina terminalis and the median eminence. A few processes terminated in the ependymal cells lining the third and lateral ventricles. The total number of immunoreactive perikarya was the highest in the brains of females sacrificed in July; it then significantly decreased until December. This variation is discussed in relation to the annual breeding cycle. PMID- 1451177 TI - Glycophorin A interacts with interleukin-2 and inhibits interleukin-2-dependent T lymphocyte proliferation. AB - Sialoglycolipids shed by tumor cells have been implicated in tumor-induced inhibition of T-lymphocyte responses to interleukin-2 (IL-2). In the present study, we have used glycophorin A, the major sialoglycoprotein of the human erythrocyte membrane, to investigate whether shedding of glycoproteins might also contribute to immunosuppression. Glycophorin A inhibited IL-2-stimulated proliferation of the IL-2-dependent cell lines HT-2 and CTLL-2 in a dose dependent manner. Time course studies on synchronized cell populations indicated that the glycoprotein acted early in the activation process. On the other hand, glycophorin A had essentially no effect on IL-1-mediated stimulation of the IL-1 sensitive thymocyte cell line EL-4 NOB-1. Gel filtration FPLC demonstrated that IL-2 was able to bind to glycophorin aggregates under physiological conditions. Reconstituted vesicles containing glycophorin were also shown to bind IL-2. In addition, both soluble glycophorin aggregates and lipid vesicles containing glycophorin blocked binding of IL-2 to high-affinity cellular IL-2 receptors. Taken together, these results suggest that shedding of tumor sialoglycoproteins with oligosaccharide chains similar to glycophorin A might contribute to negative modulation of IL-2-mediated immune responses. PMID- 1451178 TI - Phenotypic comparison of the three populations of human lymphocytes defined by CD45RO and CD45RA expression. AB - Published reports indicate that CD45RO-CD45RAbright T cells are native T cells, CD45RObrightCD45RA- T cells are memory T cells, and that concomitant loss of CD45RA expression and gain of CD45RO expression occurs during transition from naive to memory status. Thus, following in vitro activation of CD45RO- CD45RAbright T cells, a subset of transitional CD45ROdimCD45RAdim T cells is observed before conversion to a CD45RObrightCD45RA- phenotype is completed. Interestingly, all three of these phenotypic subsets are represented in the circulating human lymphocyte pool. We thus used dual-color flow cytometry to phenotypically characterize CD45RObrightCD45RA-, CD45ROdimCD45RAdim, and CD45RO- CD45RAbright lymphocytes. Both the CD45RObrightCD45RA- and CD45ROdimCD45RAdim subsets consisted almost entirely of T cells, whereas the CD45RO-CD45RAbright subset contained T cells plus essentially all of the B and natural killer cells. Additional studies used three-color flow cytometry to assess activation markers on T cells within the three subsets defined by CD45RO/CD45RA expression. CD25 expression increased with conversion from naive to memory status (5% of CD45RO CD45RAbright, 24% of CD45ROdimCD45RAdim, and 42% of CD45RObrightCD45RA- T cells), whereas CD38 expression decreased during conversion (76, 53, and 27%, respectively). We also assessed the fluorescent intensities of CD11a, CD2, and CD44, shown by others to be increased on memory, compared to naive T cells. Visual inspection of fluorescence cytograms confirmed these findings, and further showed that transitional T cells express these markers at levels indistinguishable from those for naive T cells. These findings suggest that acquisition of CD25 and loss of CD38 occur relatively early in the naive-to memory transition process, being evident in the transitional cell subset. In contrast, increased expression of CD11a, CD2, and CD44 appear to represent late events, occurring after loss of CD45RA and gain of CD45RO has been completed. PMID- 1451179 TI - Down-regulation of cell surface CD4 molecule expression induced by anti-CD4 antibodies in human T lymphocytes. AB - Antigenic modulation was defined as the down-regulation of a cell surface antigen expression induced by exposure to specific antibody. We investigated the modulation of CD4 surface expression in human peripheral blood lymphocytes incubated in vitro with anti-CD4 monoclonal antibodies (mAbs). Modulation of surface CD4 was achieved at 37 degrees C, but not at 4 degrees C, with five different murine anti-CD4 mAbs of IgG1 and IgG2a subclasses, with different epitope specificities. Modulation was dose dependent with a maximum at nonsaturating mAb concentration. It was reversible upon culture in mAb-free medium. It was accelerated and amplified in the presence of monocytes or after cross-linking of anti-CD4 mAbs. It could be induced with solid phase anti-CD4 mAbs, but not with soluble F(ab')2 fragments. Its magnitude was identical on all CD4+ lymphocytes. It was associated with a moderate down-regulation of CD2 and CD3 but not of CD8 and HLA class I surface expression. Modulation was slightly augmented by addition of inhibitors of the endosome/lysosome pathway but not by protein synthesis inhibitors. The anti-CD4 mAb initially bound to cell surface was no longer detectable after 24 hr of culture. Most of surface CD4 proteins complexed with antibody were rapidly internalized and transiently replaced by CD4 from an intracytoplasmic pool and then no longer were expressed. CD4 mRNA was moderately decreased in cells incubated with anti-CD4 mAb while beta-actin and beta 2-microglobulin mRNAs remained at stable levels. It was concluded that down regulation of CD4 surface expression induced by anti-CD4 mAb concerned only a part of CD4 molecules and was associated with a decreased synthesis. The delay required to achieve maximal modulation is likely to reflect exhaustion of the intracytoplasmic recycling pool of CD4 molecules. PMID- 1451180 TI - Enhancement of antigen-induced interleukin 4 and IgE production by specific IgG1 in murine lymphocytes. AB - Conalbumin (CA)-specific type 2 helper T cell (Th2) clone, D10G4.1 (D10) produces IL4 when stimulated with varying doses of TNP-CA in the presence of mitomycin C treated C3H spleen cells or purified B cells as antigen-presenting cells (APC). The production of IL4 was assessed by bioassay and by expression of IL4 mRNA. IL4 production reached maximum at 100 micrograms/ml of TNP-CA, whereas 1 microgram/ml of the antigen induced less than 10% of the maximum level of IL4. This lower level of IL4 production was augmented to the maximum level when monoclonal anti TNP IgG1 was added to the culture at 0.5-1 microgram/ml. Anti-TNP IgE, but not anti-TNP IgM, was also effective, though IgE was 1/10 as effective as IgG1. IgG1 with an irrelevant specificity and F(ab')2 of anti-TNP IgG1 did not show augmenting effects. Moreover, the enhancement by anti-TNP IgG1 was completely abolished by monoclonal antibody against murine Fc gamma RII, 2.4G2. These results suggest that a low dose of the antigen complexed with IgG1 is focused on APC by means of Fc gamma RII, processed, and presented efficiently to the Th2 clone. On the other hand, the co-culture of D10 with normal C3H B cells in the presence of 1-100 micrograms/ml TNP-CA resulted in polyclonal IgE production. Anti-TNP IgG1 markedly augmented the lower level of IgE production induced by a suboptimal dose of the antigen (1 microgram/ml). This augmentation was shown to be dependent on endogenous IL4 because the enhancement was abolished by monoclonal anti-IL4 (11B11). PMID- 1451181 TI - Modulation of the transcriptional rate of Fc gamma receptor mRNA in human mononuclear phagocytes. AB - Human monocytes and macrophages bear three classes of cell surface receptors for the Fc portion of IgG (Fc gamma RI, Fc gamma RII, and Fc gamma RIII). These receptors mediate phagocytosis and other effector functions and are important in the pathophysiology of hematologic disease, inflammation, and host defense. We have previously shown that interferon-gamma (IFN-gamma) and dexamethasone modulate total Fc gamma RII mRNA levels as well as Fc gamma RI and Fc gamma RII protein expression on monocytes and the monocyte-like cell line U937. In this study, we investigated the modulation of Fc gamma RI mRNA. Additionally, we utilized mRNA stability and nuclear run-on assays to study the mechanism of the modulation of Fc gamma receptor transcripts in the monocyte/macrophage cell line U937. In U937 cells, IFN-gamma increased Fc gamma RI mRNA levels 7.5-fold. Treatment with dexamethasone reduced Fc gamma RI mRNA levels to 0.6-fold of baseline and inhibited by 20-60% the increase in mRNA observed after treatment of the U937 cells with IFN-gamma. On monocytes, treatment with IFN-gamma increased monocyte Fc gamma RI mRNA 6.7-fold. Cotreatment of the IFN-gamma-stimulated monocytes with dexamethasone resulted in a 160% further increase in Fc gamma RI expression. Fc gamma RI and Fc gamma RII mRNA half-lives were then determined in U937 cells by incubation with dexamethasone and/or IFN-gamma for 16 hr and then arresting mRNA transcription with actinomycin-D (10 micrograms/ml). The mRNA half lives in untreated U937 cells were 3.3 +/- 0.3 hr (Fc gamma RI) and 3.1 +/- 0.3 hr (Fc gamma RII). For either Fc gamma RI and Fc gamma RII, the effect of dexamethasone and/or IFN-gamma on mRNA half-life was not significant (P > 0.5). We also performed nuclear run-on experiments with U937 cells which indicated that IFN-gamma increased the transcription of Fc gamma RI 4.2-fold and Fc gamma RII 1.7-fold. Our data suggest that these changes in Fc gamma RI and Fc gamma RII protein are likely due, at least in part, to increases in mRNA levels secondary to alteration in gene transcription. PMID- 1451182 TI - Differential responsiveness of immature- and mature-stage murine B cells to anti IgM reflects both FcR-dependent and -independent mechanisms. AB - Mature and immature B cells differ in their responses to antigen receptor crosslinking. Whereas mature B cells enter cell cycle in response to such stimulation, immature B cells exhibit proliferative unresponsiveness and undergo induced tolerance following surface immunoglobulin (sIg) engagement. Previous studies evaluating antigen receptor-mediated negative signaling have utilized intact goat anti-immunoglobulin (anti-Ig) antibodies as polyclonal ligands based upon observations that the Fc portion of these reagents does not interact with and mediate negative signaling through the FcR on mature B cells. Thus, the negative effects of goat anti-Ig on immature B cells have been attributed solely to signals mediated via their antigen receptors. In the studies reported here we show that the activation unresponsiveness inherent to immature B cells is FcR independent. However, we also show that immature B cells are sensitive to FcR mediated inhibition and that these effects can be mediated by intact goat antibodies at concentrations that promote positive activation signals in mature B cells. Our results demonstrate that inhibition of immature B cell LPS responses by anti-Ig antibodies, used in previous studies as an in vitro model for B cell tolerance induction, is an FcR-mediated phenomenon. We show that developmentally associated anti-Ig-mediated inhibition of LPS requires the use of intact antibodies, and that this inhibition can be blocked by the anti-FcR monoclonal antibody 2.4G2. Flow cytometric analysis of FcR-positive B cells indicates that both mature and immature B cells express equivalent levels of FcR gamma. Therefore, the sensitivity of immature, but not mature, cells to intact goat anti mu antibodies suggests that either FcRs or their associated inhibitory pathways change during B cell development. PMID- 1451183 TI - Immunological tolerance to hapten prevents subsequent induction of hapten-immune pulmonary interstitial fibrosis (HIPIF). AB - Pulmonary interstitial fibrosis (PIF) is a morphological term which in part can be defined as accumulation of collagen in the extracellular matrix. Previously we showed that hamsters sensitized with 2,4,6-trinitro-1-chlorobenzene (TNCB) developed PIF 14 days after an intratracheal challenge with 2,4,6-trinitrobenzene sulfonic acid (TNBS). The participation of delayed-type hypersensitivity (DTH) in lung collagen deposition was clearly demonstrated. In this paper, we use an adaptation of this model to mice and show that the lung collagen deposition observed was related to the genetic ability of the strain to maintain a DTH response to the immunizing hapten (TNP). Specifically, the lung collagen deposition on Day 14 in hapten-sensitized, challenged animals in high responder to TNP (BALB/c, H-2d) was higher than that in low responder mouse (C57BL/6, H 2b). Furthermore, aged C57BL/6 strain (retired breeders) possessed a DTH response to TNP and produced significantly higher accumulation of hydroxyproline than that of TNBS-challenged-only animals. A DTH mechanism for the induction of the fibrosis is consistent with the observation that responder mice that were made tolerant to the antigen were unable to respond to the lung challenge with a specific increase in lung index or collagen deposition. These results suggest that effector T lymphocytes that are important in DTH play a key role in the regulation of lung collagen deposition in hapten-immune pulmonary interstitial fibrosis (HIPIF) in mice. PMID- 1451184 TI - Mouse splenic macrophage cell lines with different antigen-presenting activities for CD4+ helper T cell subsets and allogeneic CD8+ T cells. AB - A panel of seven mouse splenic macrophage cell lines, derived from cloned progenitors, was compared for their ability to present antigen to Th1 or Th2 helper T cell lines and hybridomas, as well as to naive T cells, and to provide accessory cell function for the synthesis of antibody from primed B cells. One of the cell lines expressed MHC class II molecules and was the only line with constitutive antigen-presenting activity for Th1 cells. It may represent a subset of splenic macrophages responsible for the activation of naive Th1 helper cells in situ. The remaining six cell lines responded to INF-gamma by up-regulating their class II expression and acquiring Th1 antigen-presenting activity. They may represent cells which, in situ, lack constitutive antigen-presenting activity but are promoted to presenting status by Th1-derived INF-gamma. Five of the cell lines provided accessory cell function to Th2 cells, as indicated by antibody synthesis in suspensions of spleen cells from primed mice depleted of their antigen-presenting cells. One of the cell lines lacking accessory cell activity had constitutive antigen-presenting activity for Th1 cells. This reciprocal expression of antigen-presenting activity supports the idea that Th1 and Th2 helper cells are activated by different antigen-presenting cells. Finally, the cell lines differed in their ability to constitutively induce an allogeneic response; a response that was limited to CD8+ T cells occurred in a CD4+ helper cell-independent manner and was unaffected by the addition of INF-gamma. The alloantigen-presenting macrophage cell lines also possessed the most efficient accessory cell activity for antibody synthesis. These cell lines, which represent a spectrum of antigen-presenting activities in the spleen afford models for defining the roles of macrophages in the induction of immune responses and for resolving issues concerning their development. PMID- 1451185 TI - Human recombinant migration inhibitory factor activates human macrophages to kill tumor cells. AB - A recombinant form of human migration inhibitory factor (rMIF) obtained from COS 1 cells transfected with MIF-specific cDNA is able to activate cultured human peripheral blood monocytes and monocyte-derived macrophages, in a dose-dependent manner to become cytotoxic for tumor cells in vitro. The cytotoxicity exhibited by macrophages treated with rMIF is > or = 30% above that of cells incubated with control supernatants or with media and peaks 72 hr after the addition of tumor targets. rMIF also induces macrophages to produce tumor necrosis factor (TNF alpha) and interleukin-1 beta (IL-1 beta). These results demonstrate that rMIF is able to modulate macrophage functions and plays a role in cell-mediated immune response. PMID- 1451186 TI - A high molecular weight centrosomal protein of mammalian cells is antigenically related to myosin II. AB - Available data on the molecular composition of the centrosome, the typical microtubule-organizing center of animal cells, are still fragmentary. To address this important issue we have taken advantage of centrosome isolation from a human lymphoblastic cell line (KE37) to generate a monoclonal antibody (mAb) library. Here we present the characterization of one of these mAbs (CTR56). On the basis of both its immunofluorescence staining pattern and its reactivity with a major 200 kD antigen on immunoblots, CTR56 has been tentatively classified as an anticellular myosin heavy chain. In light of cytological and biochemical data obtained in parallel with two other well-characterized myosin antibodies, it appears that myosin cannot be considered as a genuine centrosomal protein. We have resolved the paradoxical results with CTR56 by showing that in addition to the cellular myosin heavy chain, this antibody also recognizes a high molecular weight protein specifically enriched in centrosomal fractions. The possible biological significance of this finding is discussed in structural and functional terms. PMID- 1451187 TI - Antikinetochore antibodies interfere with prometaphase but not anaphase chromosome movement in living PtK2 cells. AB - Injection of CREST antikinetochore antiserum (AKA) containing antibodies to the kinetochore into living prometaphase PtK2 cells decreased chromosome velocity to near zero. Injection of either phosphate-buffered saline or CREST antiserum without antikinetochore antibodies (antikinetochore negative: AKN) had no effect on prometaphase oscillations. AKA antiserum injected into anaphase cells at the beginning of chromatid separation had no effect on anaphase chromosome velocity, spindle elongation, or cytokinesis. Visible binding of antikinetochore antibodies in prometaphase cells at room temperature occurred between 5 and 15 minutes after injection. Anaphase cells injected at the beginning of chromatid separation had bound antibody at the end of anaphase. AKA antiserum recognizes in Western blots proteins associated with the primary constriction: CENP-B, -C, and -D, as reported by other workers. The control antiserum, AKN, does not recognize these proteins. These results imply that the antigens recognized by CREST antibodies are important for chromosome movement. Whether or not these antigens are themselves motor molecules cannot be addressed by the present data. In addition, the results suggest that these antigens are not involved in an important way in anaphase movement. PMID- 1451188 TI - [An anniversary of the Comenius University Pharmacy School in Bratislava]. PMID- 1451189 TI - [An overview of the development of pharmacy education in Slovakia]. AB - Before 1777, the pharmacist in Slovakia gained their professional qualification by practising in a pharmacy. From the establishment of the University of Trnava to 1777, they attended lectures and took examinations at its Faculty of Medicine, then from 1784 onwards in Budapest. After the establishment of Czechoslovakia, the candidates of pharmacy studied in Prague, and after the closing of Czech universities (1939) in Bratislava. Between 1940 and 1948 there existed a three year course, and later a four-year course at the Faculty of Medicine, the contents of which were close to the level of the development of sciences and the requirements of pharmaceutical practice. A logical completion of the development of the course of studies was the establishment of independent Faculties of Pharmacy in Bratislava and Brno and the prolongation of the course to five years. Commencing with the academic year 1977/78, the course of studies was divided into three specializations, General Pharmacy, Clinical Pharmacy and Technological Pharmacy. Since the academic year 1990/91 the course is uniform again, with possible differentiations in the profile of the graduate during the course according to the interests and options of the student. PMID- 1451190 TI - [Anti-inflammatory and antipyretic activity of aqua-dihydroxybenzoate copper complexes]. AB - Using screening methods, the anti-inflammatory and antipyretic activities of mononuclear otahedral complexes [composition:Cu(2,YDHB)2.H2O;dihydroxybenzoate ion - DHB; Y(n)-4(8).5(4) and 6(8)] and the corresponding carboxylic acids were studied. On paw dextran edema (rats, an effective dose of 10 mg/kg), a higher efficacy of the complexes was found as compared with the acids. All compounds significantly reduced the endotoxin pyretic reaction (rabbits, in a single dose of 20 mg/kg; in the case of the first two complexes half-dose was administered). Marked toxic effects were determined for Cu(II) salts when they were administered i.p. The observed biological activities of complexes are discussed in relation to their proposed structures. PMID- 1451191 TI - [Changes in the relative levels of fatty acids in blood and myocardium in the Prague breed of rats with hereditary hypercholesteremia after administration of slow calcium channel blockers]. AB - The present paper describes the effect of six-week oral administration of verapamil and diltiazem (1 mg.kg-1 of weight two times daily in 12 hour intervals) on the content of fatty acids of the serum and myocardium of PHHC rats. A cholesterol diet changes the content of fatty acids of the serum and myocardium of PHHC rats in comparison with control rats without the cholesterol diet. A significant decrease in the content of palmitic acid, a decrease in the content of stearic acid, linoleic acid and arachidonic acid and a significant increase in the content of oleic acid were observed in the serum. Long-term administration of the slow calcium channel blockers produces another decrease in the content of the bound form of arachidonic acid. Changes in the representation of other fatty acids are not marked. Long-term administration of a cholesterol diet produces an increase in the content of palmitic acid and stearic acid and a decrease in the content of oleic acid, linoleic acid and arachidonic acid in the myocardium. Administration of verapamil results in a modification of the above mentioned changes in all parameters excepting the content of arachidonic acid, the content of which was decreased in an even more marked manner. Administration of diltiazem produced an accumulation of both saturated and mono-unsaturated fatty acids (palmitic, stearic and oleic acids) and produced a significant decrease in the content of linoleic acid and mainly the bound form of arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451192 TI - [Substitutional relations in the expression of drug consumption]. AB - The present paper analyzes the formal equivalence of expressing the consumption of medicines in financial and physical units. The study was carried out on a representative sample of population; for the sake of the need of analytical expression also the factor of the age in the consumption of drugs measured per 1 inhabitant was taken into consideration. A highly close relationship between the two specific variables is observed. On this basis the postulate of the validity of equivalence is formulated. The paper points to the stability of this formal equivalence also in the conditions of the action of the seasonal component and the pragmatic significance of the obtained results for pharmaco-epidemiological studies is stressed. PMID- 1451193 TI - [Drug consumption of certain pharmacotherapeutic groups in relation to age and sex. Psychopharmacueticals]. AB - The paper presents data on the consumption of psycho-active drugs in the urban population, which are expressed by the number of packages and costs. The consumption of the group of agents under study represents 6.2% of total costs of drugs within the framework of out-patient care. The results of a one-year survey have revealed that the curve of the consumption of psycho-active drugs for the whole population after calculation per one person possesses the shape of a 2nd degree parabola. Consumption of psycho-active drugs per one person is significantly higher in women than in man and it consistently grows with the age. PMID- 1451194 TI - [Prescriptions for individually prepared dermatologic agents. I]. AB - The present paper reports the results of a survey of contemporary medical prescriptions of solutions, suspensions and emulsions used in dermatological practice. The obtained results were compared with the district prescription lists from Slovakia. The analysis of contemporary prescription was carried out in 27 districts in the years 1987 and 1989. The results show that 112 drugs are prescribed in the preparation of solutions. Most solutions are composite and 90% of solutions are hydrophilic. An analysis of suspensions revealed that in hydrophilic suspensions the liquid media water-glycerol or spirit-water prevail, and in hydrophobic suspensions nearly always plant oils are used. Emulsions are represented in topical extemporaneous preparations in a smaller amount than solutions and suspensions; it is 0.7% in the set under study. PMID- 1451195 TI - [Antibiotic consumption in relation to sex and age]. AB - The present paper aims at an analysis of the consumption of antibiotics in relation to age, sex and diagnosis in the district of Bratislava-vidiek. The prescription of 17 primary out-patient care physicians was evaluated. The set under study included 17,771 inhabitants divided into 10 age categories. Drug consumption was expressed by the number of packages per 1000 inhabitants and a month. The processed data were statistically evaluated. The results of the paper showed a higher consumption in women. Within the framework of the age categories under study, the consumption of antibiotics does not increase with age. The highest consumption of antibiotics, 70.45%, was found in the diseases of the respiratory system, the consumption in acute diseases being 60.46%. Tetracycline and penicillin antibiotics are the most frequently used preparations in the population under study. PMID- 1451196 TI - [Phytochemical overview of the components of Calendula officinalis L. and their therapeutic evaluation]. PMID- 1451197 TI - [The status of fluvoxamine among the antidepressive agents]. AB - Fluvoxamine was administered in an open trial of 50 hospitalized patients with major depression of the melancholic type (DSM-III-R) for an average period of 24.56 days in mean minimal and maximal daily doses of 100-311 mg orally after a wash-out interval of 1-14 days. Treatment achieved complete improvement in 54% and partial improvement in 16% of the patients, significantly more frequently in women than in men. The antidepressant effect of fluvoxamine was confirmed also by a statistically significant reduction of the global HAMD and FKD score, starting on the 7th day of the trial. The therapeutic effect was clinically apparent during the second week of treatment. The best therapeutic effect was achieved in anxiety depressions (65%), to a lesser degree inhibitory depressions (50%) and atypical ones (46%), as apparent from the value of Nahunek's antidepressive index 0.88 which suggests a significant anxiolytic effectiveness of fluvoxamine. Fluvoxamine had a positive effect on the majority of HAMD and FKD items, incl. a depressive mood, anxiety, feelings of guilt, anhedonia, reduced interest and ability, obsession, depressive thoughts and suicidal tendencies. Reduced motor activity, loss of appetite, insight, somatic symptoms, paranoidity and hypochondria were less influenced. At the onset of treatment the preparation did not reduced insomnia and thus in 72% patients hypnotics were added. In the course of fluvoxamine therapy no suicidal attempts were observed although 34 (68%) of the patients initially admitted had suicidal thoughts. Fluvoxamine is well tolerated by patients; as to side-effects gastrointestinal complaints were most frequent (in 28% of the patients). PMID- 1451198 TI - [Criteria for selection of first choice antidepressive agents]. AB - Specific inhibitors of the re-uptake of serotonin provide more adequate criteria for the selection of antidepressants of first choice, as compared with classical tricyclic antidepressants. These criteria comprise a specific therapeutic effect (e.g. influence on suicidal thoughts and action), a wider area of indications, serotonergic side-effects and relative safety of overdosage. PMID- 1451199 TI - [Fluvoxamine--pharmacologic properties]. PMID- 1451200 TI - [Fevarin--a selective serotonin uptake inhibitor. Clinical implications of serotonin selectivity]. AB - The author explains the development of specific inhibitors of serotonin re uptake. Fluvoxamine differs from classical tricyclic antidepressants by a pharmacological profile of side-effects and safety of overdosage, while the therapeutic effect is comparable. The serotonin selectivity opens perspectives of further indications. PMID- 1451201 TI - [Adrenergic and serotonergic receptors during depression and its therapy]. AB - It is supposed that adrenergic and serotonergic receptor systems can play a crucial role in pathophysiology of depressive disorder. The hypothesis are based on changes of levels of serotonin and noradrenaline and on changes of their binding sites during depression and its treatment. Study of adrenergic and serotonergic receptors by pharmacological and molecular biological methods give rise to their division to many types and subtypes. This division makes possible to study the depressive disorder and its treatment on well defined receptors systems. Decreased density of beta- and 5-HT1-receptors was found during depression. Antidepressants influence 5-HT2 and adrenergic receptors mainly. Consequently, interaction between adrenergic and serotonergic systems exerts both in the origin of depression and during the treatment. Mutual influence and cooperation of different receptors systems are the main topics of research in this field. PMID- 1451202 TI - [A short questionnaire as a means of screening for psychiatric disorders in the aged]. AB - The authors elaborated a brief questionnaire of mental health of old people. They discuss the the suitability of the self-evaluating part of the questionnaire for detection of mental disorders. Hundred and forty subjects above 65 years of age were examined: living in their homes or hospitalized at the psychiatric clinic. The mean score of the self-evaluating part of the questionnaire in the group of healthy and mentally ill differs significantly. The sensitivity of the self evaluating part for the non-differentiated group of patients is 62.07% and the specificity is 73.08%. Self-evaluation with the best reliability differentiates from healthy subjects the group of depressive patients (sensitivity 82.76%). It was revealed that self-evaluation can help also with detection of dementia (sensitivity (61.11%). An enhanced discriminating sensitivity of the questionnaire is expected from a combination of self-evaluation with items expressing objective evaluation. The authors emphasize the possibility to entrust the questionnaire to paramedical workers, and its non-pretentious character which makes it suitable for old people. PMID- 1451203 TI - [An international study of the course and outcome of schizophrenia coordinated by the World Health Organization]. AB - Psychiatry Demography Unit of Psychiatric Center Prague is one of the participating sites in the transcultural study on Long-term Course and Outcome of Schizophrenia coordinated by World Health Organization (WHO). The aim of the project is to learn more about factors predicting the long-term course and outcome and to investigate socio-cultural differences in schizophrenic patients. The present research builds upon the earlier WHO coordinated studies: International Pilot Study of Schizophrenia (IPSS) carried out in 1968-1969 in 13 centers including Czechoslovakia (N = 1202) and Study on Determinants of Outcome of Severe Mental Disorder (DOSMed) taken place between 1978-1980. The finding of IPSS and DOSMed were notable: incidence of narrowly defined schizophrenia did not vary greatly across cultures in opposite of the variation of short term outcome of illness that was more favourable in developing than in industrialized nations. The present follow-up study of the DOSMed and the IPSS patients (after 14 and 24 years) allow the examination of a large enough sample in a relatively short time and facilitate the development of new instruments, which provide a unique opportunity of their further cultural valid application for our center. PMID- 1451204 TI - [Neurotic disorders and personality disorders in the 10th revision of the International Classification of Diseases]. PMID- 1451205 TI - [Present trends in the development of drugs within the cholinesterase inhibitor group as therapeutic agents for Alzheimer's disease]. AB - With prolongation of human age rises also the incidence of senile dementia, inclusive dementia of Alzheimer's type (DAT). At the same time the authors present views in the aetiology of this illness, the role of cholinergic mechanisms of the development dementia and they mention DAT treatment strategy focusing attention on a group of drugs-cholinesterase inhibitors. PMID- 1451206 TI - [The 140th anniversary of the birth of Dr. O. Binswanger]. AB - Otto Binswanger be one of noted psychiatrist of this era. Authors get acquainted with his biography and extensive scientific, pedagogic and organize activity. PMID- 1451207 TI - Child abuse & neglect--let's focus on prevention. PMID- 1451208 TI - The ISBA year of the child. PMID- 1451209 TI - Advocating for the traumatically brain injured child. PMID- 1451210 TI - Medication administration in Illinois schools. PMID- 1451211 TI - Anaesthetic drug costs are not increased by propofol. PMID- 1451212 TI - Tracheal intubation and cervical injury. PMID- 1451213 TI - Guidelines to the practice of obstetrical anaesthesia. PMID- 1451214 TI - Anaesthesia and myasthenia gravis. PMID- 1451215 TI - Perioperative stroke. PMID- 1451216 TI - Anaesthesia and leucocyte locomotion. PMID- 1451217 TI - Neutrophils from patients undergoing hip surgery exhibit enhanced movement under spinal anaesthesia compared with general anaesthesia. AB - The purpose of this research was to investigate whether the effects of regional anaesthesia on neutrophil migration differ from those due to general anaesthesia during major orthopaedic surgery in human patients. Eighteen patients underwent spinal or general anaesthesia (halothane or isoflurane) for surgery (six patients in each group). Blood samples were taken prior to induction of anaesthesia and after surgery was in progress for one hour. The movement of isolated neutrophils was measured in both samples in the chemotactic chamber toward lipopolysaccharide activated pooled serum. In addition plasma concentrations of catecholamines were determined in the blood samples. Neutrophils extracted from peripheral blood during spinal anaesthesia and surgery moved further towards a complement-derived attractant than neutrophils obtained from patients undergoing surgery under general anaesthesia with halothane or isoflurane and surgery (156.4 +/- 7.6 microns vs 114.3 +/- 6.1 microns or 119 +/- 8.4 microns respectively, P < 0.05). Increased concentrations of adrenaline were present in both general anaesthetic groups whereas the spinal group had lower concentrations than those prior to anaesthesia and surgery. It is considered unlikely that these differences in neutrophil reactivity are due to the direct effects of anaesthetic agents employed. The effects are likely to be the result of differing effects of spinal anaesthesia on the stress response or immunological mediators. PMID- 1451218 TI - Epidural morphine reduces halothane MAC in humans. AB - The effect of epidural morphine sulphate (4 mg in 10 ml saline) on the minimum alveolar concentration of halothane was investigated in a double-blind, randomized fashion in ten adult patients undergoing abdominal surgery, and compared with the minimum alveolar concentration of halothane after epidural administration of 10 ml saline in a similar group of patients. Morphine sulphate, administered through the epidural catheter 98 +/- 33 min before to skin incision reduced the minimum alveolar concentration of halothane by 28% (0.57% vs 0.78%, P < 0.05). PMID- 1451219 TI - Spinal anaesthesia with lidocaine 2% for caesarean section. AB - Spinal anaesthesia with 2, 2.5 or 3 ml of glucose-free lidocaine 2% was studied in 50 patients undergoing Caesarean section. Onset time, cephalad spread of analgesia, quality of analgesia, muscle relaxation, the cardiovascular effects and duration of analgesia and motor block were assessed. Reliable anaesthesia was provided with 2.5 and 3 ml while 2 ml of 2% lidocaine was insufficient. Onset time varied between 5.5 to 6 min and maximum cephalad spread was achieved in 10 15 min. The mean maximum extent of sensory analgesia was higher after 2.5 ml (T4.1) and 3 ml (T3.6) than after 2 ml (T7) (P < 0.001). Complete motor block was achieved in all the patients. The mean duration of sensory block was 123 +/- 6.23 min (2 ml) to 126 +/- 7.53 min (2.5 and 3 ml). The mean duration of motor block in 2.5 and 3 ml groups was higher (P < 0.001) than in the 2 ml group and was correlated with the dose of lidocaine (P < 0.05). Hypotension (SBP < 100 mmHg) was noted in 10% (n = 5) of patients in whom the cephalad spread of analgesia was also higher. All the neonates had an apgar score of 7 or more at 1 min. These results suggest that 2.5 to 3 ml of 2% lidocaine provides satisfactory anaesthesia for Caesarean section. PMID- 1451220 TI - Hyaluronidase improves regional ophthalmic anaesthesia with etidocaine. AB - The effect of adding hyaluronidase to regional ophthalmic anaesthesia with etidocaine 1.5% was examined. Two studies were performed in a double-blind fashion. In Study #1, 70 patients were given peribulbar anaesthesia with etidocaine either with or without hyaluronidase (7.5 IU.ml-1) using a standard intraorbital injection and separate lid injections. The block was supplemented as needed. Lower intraorbital volumes (6.4 +/- 2.2 ml vs 8.2 +/- 2.3 ml, P < 0.01) and improved scores for globe akinesia (P < 0.01), lid akinesia (P < 0.01) and analgesia (P < 0.05) were recorded in the hyaluronidase group than in the plain etidocaine group. In Study #2, 80 patients were randomized to receive etidocaine and hyaluronidase either at a concentration of 7.5 IU.ml-1 or 15 IU.ml-1 using a two-injection-site technique. No differences were noted in the volumes of local anaesthetics required or in the success rates between the two groups. It was concluded that the addition of hyaluronidase to etidocaine decreases the volume needed and improves the quality of block compared with plain etidocaine. Doubling the dose of hyaluronidase does not improve the effectiveness of block. PMID- 1451221 TI - Treatment of intraoperative hypertension with enflurane, nicardipine, or human atrial natriuretic peptide: haemodynamic and renal effects. AB - The purpose of this study was to assess the effects of the calcium entry blocker nicardipine and alpha human atrial natriuretic peptide (hANP) on antihypertensive and diuretic activity in hypertensive surgical patients. The site of the diuretic actions of these drugs along the nephron were also investigated by measuring the excretion rate of inorganic phosphate (PO4). Hypertension during gastrectomy was treated by increasing the concentration of enflurane, by nicardipine infusion (0.5-2.0 micrograms.kg-1 x min-1), or by hANP infusion (0.05-0.2 microgram.kg-1 x min-1) under general anaesthesia. Enflurane, nicardipine and hANP all decreased arterial pressure to the same extent. Urine flow, Na and PO4 excretion increased following the administration of nicardipine or hANP. Fractional distal reabsorption of sodium was suppressed from 89.7 +/- 2.8% to 82.1 +/- 5.0% by the hANP, but not by the nicardipine infusion. Creatinine clearance was increased by hANP infusion, but did not change in the nicardipine group. It is concluded that nicardipine and hANP can be used safely for the treatment of hypertension during surgery. Both drugs induced phosphaturic diuresis, but the site of action of the two drugs on the nephron may be different. Phosphate reabsorption is considered to occur largely in the renal proximal tubule, so that its appearance in the urine in increased quantities without the change of renal circulation in the nicardipine group suggests a proximal tubular action of this drug. However, the site of action of hANP in the kidney was not determined because GFR increased and distal sodium reabsorption was suppressed due to the drug infusion. PMID- 1451222 TI - Anaesthetic technique does not influence postoperative bowel function: a comparison of propofol, nitrous oxide and isoflurane. AB - The aim of this study was to evaluate the influence of propofol, nitrous oxide and isoflurane on recovery, postoperative bowel function and postoperative complications after major gastrointestinal surgery. Sixty patients undergoing elective colonic operations were included in the study. They were randomly allocated to anaesthesia with isoflurane-nitrous oxide, propofol-air, or propofol nitrous oxide, with fentanyl and vecuronium being used in all three groups. The same anaesthetic and surgical teams performed all the operations. The postoperative course was judged once each day by the Acute Physiology Score (APS) based on the Apache II classification, passage of gas, tolerance of enteral feeding, hospital stay and complications up to 30 days after surgery. The demographic data, magnitude of operation, duration of operation, intraoperative blood loss, and post-operative analgesic needs were similar in the groups. In all groups the APS was normal by median day 1 (range 1-7). A similar impairment of bowel function after operation, with passage of gas median 3 (1-6) days after surgery and tolerance of enteral intake median day 5 (1-10), was found in all groups. The incidence of complications and the length of postoperative hospital stay, median 11 (6-45) days, did not differ among the groups. It is concluded that overall recovery, bowel function, postoperative hospital stay, and complications were not influenced by the anaesthetic technique. PMID- 1451223 TI - Alfentanil sedation for cardiac catheterization of children with Fontan shunts. AB - After Fontan operation, prolonged invasive cardiac assessment is often needed. This study is a clinical evaluation of the effectiveness of flunitrazepam premedication, EMLA cream, and alfentanil continuous infusion for management of children undergoing such catheterization. Fourteen consecutive subjects aged 5-20 yr with Fontan shunts (right atrium to pulmonary artery) undergoing elective haemodynamic and electrophysiological catheterization were sedated with an individually titrated alfentanil infusion. After oral premedication with flunitrazepam 2 mg, the mean induction dose and mean maintenance requirement of alfentanil were 4.4 +/- 2.7 micrograms.kg-1 and 10.3 +/- 8.6 micrograms.kg-1 x hr 1, respectively. Mean oxygen consumption during haemodynamic catheterization was 4.1 +/- 0.4 ml.kg-1 x min-1 with an average individual variation of 10%. For every patient, tranquil and stable conditions during catheterization could be produced. It is concluded that alfentanil infusion is a method of sedation of children and adolescents with Fontan shunts during haemodynamic and electrophysiologic catheterization. However, continuous monitoring of ventilation and an understanding of the slow circulation time after Fontan operation are essential with such sedation in these patients. PMID- 1451225 TI - Pulmonary arteriovenous fistula: mechanical ventilation and hypoxemia. AB - Pulmonary arteriovenous malformation (PAVM) is an uncommon congenital anomaly. As PAVM is a direct communication between branches of the pulmonary artery and vein, major disturbances in gas exchange can result. We present a patient with an unsuspected PAVM who came to our institution for drainage of a brain abscess. Arterial blood gas analysis during and after surgery demonstrated a large alveolar-arterial gradient for oxygen in the absence of any obvious pulmonary pathology while the patient was receiving positive pressure ventilation (PPV). Oxygenation improved considerably upon resumption of spontaneous ventilation. A diagnosis of PAVM was made subsequently. We conclude that positive pressure ventilation can worsen right to left shunting in patients with PAVM. PMID- 1451226 TI - Multicore myopathy in a patient with anhidrotic ectodermal dysplasia. AB - We report a patient with multicore myopathy, a rare myopathy not previously reported in the anaesthetic literature. It is characterised by a myopathy of proximal muscles which tends to follow a benign course but may be associated with a severe form of cardiomyopathy. The myopathy is related to central core disease so these patients should be considered to have a potential for developing malignant hyperthermia. Complicating this case was an associated anhidrotic type of ectodermal dysplasia resulting in the absence of sweating, febrile episodes, recurrent pulmonary infections, conical and missing teeth, scaly skin and fine, sparse hair. The patient had a scoliosis repair which was uneventful but died three weeks later following a major pulmonary aspiration while on the ward. The cause of the aspiration is thought to have been unsuspected laryngeal incompetence associated with ectodermal dysplasia, the myopathy involving his bulbar muscles and analgesic medication. PMID- 1451224 TI - The use of muscle relaxants in the intensive care unit. AB - Neuromuscular blocking agents are frequently used in the Intensive Care Unit to facilitate tracheal intubation and the application of continuous paralysis. This review will focus on various conditions of the critically ill patient such as multi-organ dysfunction, acid-base and electrolyte imbalance, prolonged immobility, multiple drug interactions and specific disease/injury processes that may affect the pharmacokinetic and pharmacodynamic behaviour of muscle relaxants. As such, due to the complex nature of the critically ill patients, the effects of neuromuscular blocking agents are unpredictable. Therefore, guidelines regarding their administration and the methodology and requirement for continuous bedside monitoring of neuromuscular function will be presented. PMID- 1451227 TI - Kinetics of dissolution of gaseous halothane in Krebs-Ringer's solution. AB - The responses of biological tissues to volatile anaesthetics are commonly studied by incubating specimens in a bath containing dissolved anaesthetic. One accepted technique is to bubble an anaesthetic gas into several incubation chambers simultaneously. To assess the validity of this technique in producing dissolved anaesthetic (the biologically active form) at equal rates among the several chambers, we determined the kinetics of dissolution of halothane gas in three tissue incubation chambers containing Krebs-Ringer's solution. We found that (1) the dissolution kinetics were first-order in all three chambers; (2) the rate of halothane dissolution depended on the gas bubbling rate; (3) even with the same bubbling rates, chamber shapes and chamber volumes, the dissolution rates for the three chambers were not equal, suggesting that dissolution rate depended on small differences in chamber geometry; (4) the dissolution rates could be made equal by adjusting chamber bubbling rates according to calculations involving the first order rate equation; and (5) the maximum coefficient of variation of dissolved halothane concentration was 9% at 63% approach to equilibrium and 3% at equilibrium. PMID- 1451228 TI - Arterial baroreflex attenuation during and after continuous propofol infusion. AB - The reduction of arterial blood pressure produced by propofol may be, in part, attributable to impaired baroreflex integrity. The purpose of this study was to investigate arterial baroreflex sensitivity during and after continuous propofol infusion. In urethane anaesthetized rabbits, left renal sympathetic nerves were exposed and placed on a bipolar silver electrode to record renal sympathetic nerve activity (RSNA). Mean arterial pressure (MAP) via a femoral artery and heart rate (HR) by electrocardiogram were continuously recorded. The rabbits were divided into two groups of eight each: Group 1, propofol 5 mg.kg-1 bolus followed by infusion 0.5 mg.kg-1 x min-1; Group 2, propofol 2 mg.kg-1 bolus followed by 0.2 mg.kg-1 x min-1. Phenylephrine pressor and sodium nitroprusside (SNP) depressor tests were carried out before propofol was started (control), at 15 and 30 min during 30 min infusion, and at 15, 30 and 60 min after its discontinuation. The change of RSNA was plotted with respect to every 5 mmHg increment and decrement of MAP to construct sympathetic baroreflex sigmoid curves, and to evaluate baroreflex sensitivity. The baroreflex sensitivity was also evaluated by calculating the ratio of maximum increase of RSNA or HR to SNP induced maximum decrease of MAP (delta RSNA/delta MAP, delta HR/delta MAP). Despite the same decreases or increases in MAP, RSNA was attenuated after 15 and 30 min of propofol infusion in both groups compared with control (P < 0.05). Decreased delta RSNA/delta MAP gradually returned to the control level 60 min after discontinuation of propofol in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451229 TI - Lupus anticoagulant, paramyotonia congenita and pregnancy. AB - A case report is presented of the anaesthetic management of a parturient with paramyotonia congenita and lupus anticoagulant antibodies. She had been treated with prophylactic, subcutaneous heparin and aspirin throughout her pregnancy. Epidural analgesia was provided for labour and delivery. PMID- 1451230 TI - Inspiratory valve malfunction in a circle system: pitfalls in capnography. AB - Capnography is a useful technique in monitoring the integrity of anaesthetic equipment such as the malfunctioning of unidirectional valves in circle system. However, the lack of a precise mechanism in existing capnographs to identify the start of inspiration and the beginning of expiration in the capnograms, makes the analysis of the carbon dioxide waveforms during inspiration difficult and thus results in inaccurate assessment of rebreathing. We report a case where, during the malfunction of the inspiratory unidirectional valve in the circle system, the capnograph failed to detect the presence of substantial rebreathing. Critical analysis of the capnogram recorded during the malfunction revealed that there was substantial rebreathing which was underestimated by the capnograph as it reports only the lowest CO2 concentration rebreathed during inspiration in such abnormal situations. PMID- 1451231 TI - Antitumor activity of treosulfan against human breast carcinomas. AB - Treosulfan (L-threitol-1,4-bismethanesulfonate, Ovastat) is a bifunctional alkylating agent that shows a formal structural similarity to busulfan and is applied clinically to patients suffering from ovarian cancer. The present study demonstrated the pronounced antitumor activity of this drug against three of five human breast carcinomas xenografted to athymic mice. It was shown that treosulfan is capable of inducing irreversible and complete remission of the heterotransplanted human breast carcinomas MDA-MB-436 and MX-1 within 14 days after drug application and of effecting growth inhibition by more than 90% in the MDA-MB-435S xenograft. In all three carcinomas, treosulfan caused more pronounced growth reduction than did equitoxic doses of the alkylator cyclophosphamide. Adriamycin, an intercalating cytostatic agent that is an important component of clinical nonhormonal chemotherapy of breast carcinomas, induced only partial remission of these three xenografts and inhibited the tumor growth by 80%-90% (MDA-MB-436, MX-1) and by 70%-80% (MDA-MB-435S), respectively. In the M 3 xenograft, treosulfan just led to a retardation and stagnation of tumor growth; it was again more effective than Adriamycin but was clearly less active than cyclophosphamide. The FM 2 breast carcinoma, finally, was the only xenograft whose growth was not influenced by treosulfan at doses up to that which was lethal to 50% of the treated mice (LD50 value). These results confirm that treosulfan is effective against human breast carcinomas. Because of this activity as well as the known low toxicity and good clinical compatibility of treosulfan, it should be considered for introduction into nonendocrine chemotherapeutic regimens against human breast carcinomas and investigation in clinical trials. PMID- 1451232 TI - Hepatic intra-arterial infusion of fotemustine: pharmacokinetics. AB - Fotemustine is a new nitrosourea derivative that contains an alpha aminophosphonic acid and has a short half-life and a high plasma clearance. As myelosuppression occurs as the dose-limiting toxicity, local drug delivery has been investigated in the treatment of liver metastases arising from colorectal cancer. A pharmacokinetic study was undertaken in patients who received either i.v. or hepatic intra-arterial (HIA) infusion of 100 mg/m2 fotemustine so as to estimate the advantage of local chemotherapy, considering the pharmacokinetic differences between the two routes together with the resultant toxicities (when available). Our findings substantiated the hypothesis that a 4-h HIA infusion of foetmustine would result in a lower exposure of healthy tissues to the drug, since the AUC measured in systemic plasma was reduced by approximately 50% following such treatment as compared with i.v. infusion. This reduction in AUC should indicate a manyfold increase in exposure of the liver tumour to the alkylating properties of the drug, since it represents the proportion of the dose that has degraded within the liver. The first-pass liver-extraction ratio of fotemustine given as a 4-h HIA infusion, which ranged from 0.4 to 0.9 as estimated in patients receiving i.v. and HIA infusions in a cross-over study, argues for further investigation of HIA foetemustine infusion for the treatment of liver metastases so as to increase the response rate and decrease the occurrence of major toxic side effects in such patients. PMID- 1451233 TI - Intrathecal 5-fluorouracil in the rhesus monkey. AB - Because meningeal spread of both leukemia and solid tumors remains a difficult therapeutic problem, there is a compelling need to develop new agents for intrathecal administration. 5-Fluorouracil (5FU), an active anticancer agent, penetrates into the central nervous system to some degree following intravenous dosing. Significant systemic toxicity, however, is associated with this route of administration. Therefore, the pharmacokinetic behavior of 5FU following its intrathecal administration was studied in a rhesus monkey model. After a 10-mg intraventricular dose, the disappearance of the drug from ventricular cerebrospinal fluid was monoexponential, the half-life being 51 min; the area under the concentration-time curve (AUC) being greater than 18 mM h-1; and the peak ventricular 5FU concentrations ranging between 10 and 15 mM. After a 1-mg intralumbar dose, the AUC was 1235 microM h-1. No toxicity was observed following intraventricular administration of 5FU. After intralumbar administration of either a 10-mg or a 1-mg dose, however, local toxicity was observed in the lumbar spinal cord. These findings suggest that intrathecal administration of 5FU is not presently a feasible means of achieving cytotoxic cerebrospinal fluid concentrations. PMID- 1451234 TI - Nitric oxide: its production in host-cell-infiltrated EMT6 spheroids and its role in tumour cell killing by flavone-8-acetic acid and 5,6-dimethylxanthenone-4 acetic acid. AB - Flavone-8-acetic acid (FAA) and its more dose-potent analogue 5,6 dimethylxanthenone-4-acetic acid (5,6-MeXAA), appear to exert their antitumor effects through vascular and other host-mediated mechanisms and are known to induce the synthesis of nitric oxide by murine macrophages. We investigated the role of nitric oxide in the cytotoxic effects of these drugs in host-cell infiltrated spheroids. EMT6 murine mammary adenocarcinoma cells were grown in culture to produce multicellular spheroids in vitro spheroids), which were then inoculated i.p. into mice. After 6 days the spheroids were removed ex vivo spheroids). Exposure to FAA (890 microM) and 5,6-MeXAA (80 microM) in vitro for 20 h increased nitrite concentrations to 6.7 and 9.7 nmol/spheroid, respectively, as compared with 0.7 nmol/spheroid in the absence of drug. FAA and 5,6-MeXAA did not increase nitrite production in in vitro spheroids in cells obtained by peritoneal lavage. However, mixed cultures of in vitro spheroids and peritoneal cells treated with 5,6-MeXAA produced nitrite (2.4 nmol/spheroid), indicating that interactions between host cells and tumour cells were important for induction. The effects of these drugs on ex vivo spheroids were prevented by co incubation with NG-monomethyl-L-arginine, indicating that nitrite originated from the oxidation of L-arginine to nitric oxide. Cell sorting of disaggregated spheroids into EMT6 cells and Mac-1-positive macrophage populations indicated that both of these cell populations could be induced to synthesise nitric oxide by subsequent incubation with 5,6-MeXAA. Incubation of ex vivo spheroids with FAA and 5,6-MeXAA decreased the clonogenicity of EMT6 cells, and this effect was wholly (FAA) or partially (5,6-MeXAA) reversed by the presence of NG monomethylarginine (250 microM). FAA and 5,6-MeXAA may therefore exert some of their cytotoxic effects on tumour cells through the production of nitric oxide. PMID- 1451235 TI - Analysis and pharmacokinetics of N-l-leucyldoxorubucin and metabolites in tissues of tumor-bearing BALB/c mice. AB - Leucyldoxorubicin (Leu-Dox) was developed as a prodrug of doxorubicin (Dox) with the aim of lowering the cardiotoxicity and improving the therapeutic index produced by Dox. To support the preclinical findings on its antitumor activity and cardiotoxicity, concentrations of Leu-Dox and its metabolites were determined in plasma, heart, and tumor after the administration of Leu-Dox to tumor-bearing mice. A liquid-liquid extraction procedure employing a chloroform/2 propanol/dimethylsulfoxide (DMSO) mixture was developed. By means of high performance liquid chromatography (HPLC) with fluorescence detection, Leu-Dox and six of its metabolites could be assayed in the tissues with high sensitivity. Detection limits ranged from 0.01 nmol/g tissue for the aglycons to 0.06 nmol/g for Dox. Recoveries were in the range of 82%-110%, and calibration curves were linear over the concentration range tested (0.1-10 nmol/g tissue, r > or = 0.998). Concentration versus time curves were constructed for plasma, heart, and tumor over the first 72 h, and areas under the curves (AUCs) for the first 48 h were determined by the trapezoidal rule. Dox was rapidly formed from Leu-Dox, reaching peak levels in plasma within 5 min and in tissues within 1 h after i.v. administration of Leu-Dox (12 mg/kg). The elimination of Leu-Dox was also fast as illustrated by final half-lives of 1.1, 0.8, and 0.9 h in the plasma, heart, and tumor, respectively. For Dox, the final half-lives were 16.7 h in plasma, 15.3 h in heart tissues, and 27.4 h in tumor tissues. AUC values determined for Leu-Dox and Dox were 221 and 51 nmol ml-1 min, 443 and 4,262 nmol g-1 min, and 153 and 1,466 nmol g-1 min in the plasma, heart, and tumor, respectively. Comparison of these values with those obtained after an equimolar dose of Dox indicated 26%, 30%, and 16% of Leu-Dox appeared as Dox in the plasma, heart, and tumor, respectively. Thus, not only is the plasma compartment not representative for calculations of the conversion of Leu-Dox into Dox in tissue, but differences in its appearance also exist between the tissue compartments. The AUC values found for Dox in the heart may explain the reduced cardiotoxicity elicited by Leu-Dox as compared with Dox; however, the values obtained for Dox in the insensitive murine colon tumor cannot explain the enhanced antitumor activity exerted by Leu Dox in the sensitive human tumor xenografts in nude mice. PMID- 1451236 TI - Multicenter phase II trial of brequinar sodium in patients with advanced squamous cell carcinoma of the head and neck. AB - A total of 19 patients with advanced squamous-cell carcinoma of the head and neck who had not previously been exposed to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given intravenously at a median weekly dose of 1,200 mg/m2. The toxicity was moderate, with 7 patients (37%) experiencing grade 3 or 4 toxicity. In all, 16 patients who were evaluable for efficacy showed no objective response. We conclude that brequinar given at this dose and on this schedule has no significant activity in advanced squamous-cell carcinoma of the head and neck. PMID- 1451237 TI - Is metabolism an important arbiter of anticancer activity of ether lipids? Metabolism of SRI 62-834 and hexadecylphosphocholine by [31P]-NMR spectroscopy and comparison of their cytotoxicities with those of their metabolites. AB - Antineoplastic ether lipids have entered phase I clinical trial and, although their mechanism of action remains unclear, it is widely believed that the plasma membrane is the primary cellular drug target. In the present study the hypothesis was tested that metabolism of ether lipids acts as a detoxification process. [31P]-nuclear magnetic resonance (NMR) spectroscopy was used to study the metabolism of the ether lipid SRI 62-834 (SRI) and the phosphate ester hexadecylphosphocholine (HPC) in the presence of both isolated phospholipases C and D and post-mitochondrial rat liver homogenate. Both SRI and HPC were slowly metabolised by phospholipase D to their alkyl phosphates and choline, and the alkyl phosphates were subsequently metabolised by phosphatase to yield the alcohols and inorganic phosphate. These studies failed to detect any metabolism of either SRI or HPC by phospholipase C, and the metabolism of platelet activating factor (PAF) by this enzyme was not inhibited by the addition of either compound. The cytotoxicity of SRI, the related compound HPC and their metabolites was determined in vitro using three cell lines. Cytotoxicity was measured by analysis of cell growth kinetics, MTT assay and lactate dehydrogenase release. Closely similar results were obtained in the JB1 rat hepatoma cell line, in the non-transformed BL8 rat hepatocyte cell line, and in A549 human lung adenocarcinoma cells. SRI was the most toxic of the compounds analysed, the concentration required to produce 50% toxicity or growth inhibition (IC50) being 6-9 microM. The putative metabolite of SRI, 2,2' bis(hydroxymethyl)tetrahydrofuran, and the known metabolites [2' (octadecyloxymethyl)tetrahydrofuran-2'-yl]methyl phosphate and 2-hydroxymethyl-2 octadecyloxymethyltetrahydrofuran exhibited IC50 values of > 200, > 100 and 40-70 microM, respectively, consistent with metabolic detoxification. HPC was more cytotoxic (IC50, 37 microM) than its phosphate metabolite (IC50, 140 microM), but its toxicity was similar to that of its metabolite hexadecanol (IC50, 28 microM), suggesting that only the former metabolic route leads to detoxification. PMID- 1451238 TI - Schedule-dependent synergistic action of tiazofurin and dipyridamole on hepatoma 3924A cells. AB - Tiazofurin is an oncolytic nucleoside analog that has shown therapeutic activity in end-stage acute non-lymphocytic leukemia and in chronic granulocytic leukemia in blast crisis. Tiazofurin is anabolized to the active metabolite, TAD, which inhibits IMP dehydrogenase activity, leading to a reduction in guanylate pools and to the cessation of neoplastic cell proliferation. The drug exhibits potent cytostatic and cytotoxic activity against hepatoma 3924A cells in culture. In growth-inhibition and clonogenic assays, the 50% inhibitory concentration of tiazofurin was 3.8 and 4.2 microM, respectively. Dipyridamole, an inhibitor of nucleoside transport, curtails the salvage of nucleosides and bases for nucleotide biosynthesis. Dipyridamole exhibited cytotoxicity against hepatoma 3924A cells, with an LC50 of 24 microM and an IC50 of 29 microM being recorded. A combination of tiazofurin and dipyridamole provided synergistic cytotoxicity in hepatoma 3924A cells in culture. This synergistic activity was dependent on the order of addition of the drugs. Simultaneous addition of the two drugs produced antagonism, whereas preincubation of cells with tiazofurin or dipyridamole followed by addition of the second drug resulted in synergy. TAD concentrations were significantly higher (129% and 135%) in cells that had been pretreated with tiazofurin or dipyridamole before the addition of the second agent as compared with cells that had been treated simultaneously (113%). These studies indicate the importance of the order of the addition of drugs to obtain a synergistic response in combination chemotherapy and suggest the need for a careful selection of drug modulation in clinical trials of tiazofurin and dipyridamole. PMID- 1451239 TI - Myocardial 'stunning' in man. PMID- 1451240 TI - Interposed abdominal compression-cardiopulmonary resuscitation and resuscitation outcome during asystole and electromechanical dissociation. AB - BACKGROUND: Coronary perfusion pressure has been shown to be a significant determinant of return of spontaneous circulation from cardiac arrest during asystole and electromechanical dissociation. The addition of interposed abdominal compression to otherwise standard cardiopulmonary resuscitation (CPR) increases coronary perfusion pressure in animal and human models. METHODS AND RESULTS: Accordingly, we conducted a randomized prospective study of 143 consecutive patients experiencing cardiac arrest in a large university-affiliated teaching hospital in whom the initial arrest rhythm was asystole or electromechanical dissociation. Patients were randomized to receive either interposed abdominal compression-CPR or standard CPR. The two end points studied were return of spontaneous circulation and 24-hour survival. In addition, we studied the complications associated with interposed abdominal compression-CPR. Sixty-nine men and 74 women with a mean age of 64 years (range, 19-97 years) were studied. The overall rate of return of spontaneous circulation was 38%. Return of spontaneous circulation was significantly greater in the group receiving interposed abdominal compression-CPR compared with the group receiving standard CPR (49% versus 28%, p = 0.01). At 24 hours, there was a significantly greater number of patients alive in the experimental group than in the control group (33% versus 13%, p = 0.009). We found no complication directly related to the procedure of interposed abdominal compression in a small subset of patients who died and underwent necropsy. CONCLUSIONS: We conclude that the addition of interposed abdominal compression may be a useful adjunct to otherwise standard CPR that can improve resuscitation outcome of patients experiencing in-hospital cardiac arrest from asystole and electromechanical dissociation. PMID- 1451241 TI - Evaluation of colestipol/niacin therapy with computer-derived coronary end point measures. A comparison of different measures of treatment effect. AB - BACKGROUND: The Cholesterol Lowering Atherosclerosis Study has demonstrated beneficial effect of colestipol/niacin on coronary atherosclerosis using a panel determined global coronary change score. We now report treatment group comparisons using quantitative coronary angiographic (QCA) measures from all processable segments in 85 of 162 randomly selected baseline/2-year film pairs. METHODS AND RESULTS: Treatment benefit was established for percent stenosis for either continuous or categorical analyses with regression established regardless of the per-patient scoring procedure. In addition, treatment benefit favoring regression was established in some cases for roughness and for percent involvement, a longitudinal estimate of the percent of coronary surface involved by raised lesions. Benefit on minimum diameter was directly related to whether the segment was proximal to a graft insertion and hemodynamically related to the bypass graft. QCA correlates of panel-determined progression were increases in percent stenosis and numbers of occluded lesions in native arteries and the number of progressing lesions in bypass grafts. CONCLUSIONS: These results demonstrate that a variety of computer measures can be used as end points in coronary angiographic therapy trials, but change in percent stenosis correlates best with visual panel assessments and best reflects the treatment benefit; when treatment effect sizes are moderate to large, the required sample size of coronary angiographic trials can be reduced when QCA is used. PMID- 1451242 TI - A prospective, placebo-controlled, randomized trial of intravenous streptokinase and angioplasty versus lone angioplasty therapy of acute myocardial infarction. AB - BACKGROUND: The value of routine administration of intravenous thrombolytic agents during percutaneous transluminal coronary angioplasty (PTCA) therapy of acute myocardial infarction (MI) has not been determined. Therefore, we prospectively randomized 122 patients with evolving MI to PTCA therapy with or without adjunctive intravenous streptokinase therapy. METHODS AND RESULTS: Patients with ECG ST segment elevation who presented within 4 hours of symptom onset, had no contraindication to thrombolytic therapy, and were not in cardiogenic shock were enrolled. They were treated immediately with intravenous heparin (10,000 units) and oral aspirin (325 mg) and randomized to treatment with placebo or streptokinase (1.5 M units) administered intravenously over 30 minutes. Patients then were taken immediately to the catheterization laboratory, and those with suitable coronary anatomy underwent immediate PTCA. Subsequent clinical course, serial radionuclide ventriculography, and 6-month repeat angiography were analyzed. A total of 106 patients were treated with PTCA. Use of PTCA was similar for placebo (92%) and streptokinase (83%) groups. Angioplasty was successful in 95% of patients, with no difference in placebo (93%) and streptokinase (98%) groups. Serial radionuclide ventriculography demonstrated no difference in 24-hour (52 +/- 12% versus 50 +/- 12%) or 6-week (51 +/- 12% versus 51 +/- 13%) ejection fraction values for placebo and streptokinase groups, respectively. Contrast ventriculography demonstrated improvement in immediate (54 +/- 12%) versus 6-month (60 +/- 15%, p < 0.05) values for the overall group. No differences in 6-month values were present (58 +/- 15% versus 62 +/- 15%, p = NS) for placebo and streptokinase groups, respectively. Coronary angiography was performed in 75% of the 90 patients eligible for restudy. Arterial patency was 87% at 6 months, and coronary restenosis was present in 38% of patients. No differences in chronic patency or restenosis were detected for the two treatment groups. Although adjunctive intravenous streptokinase therapy did not improve outcome, it did complicate the hospital course. Hospitalization was longer (9.3 +/- 5.0 versus 7.7 +/- 4.4 days, p = 0.046) and more costly ($25,191 +/- 15,368 versus $19,643 +/- 7,250, p < 0.02). Transfusion rate was higher (39% versus 8%, p = 0.0001) and need for emergency coronary bypass surgery was greater (10.3% versus 1.6%, p = 0.03) for the streptokinase-treated patients. CONCLUSIONS: Adjunctive intravenous streptokinase therapy does not enhance early preservation of ventricular function, improve arterial patency rates, or lower restenosis rates after PTCA therapy of acute MI. Hospital course is longer, more expensive, and more complicated. For these reasons, PTCA therapy of acute MI should not be routinely performed with adjunctive intravenous streptokinase therapy. PMID- 1451243 TI - Mitral valve replacement with and without chordal preservation in patients with chronic mitral regurgitation. Mechanisms for differences in postoperative ejection performance. AB - BACKGROUND: Standard mitral valve replacement (MVR) in patients with chronic mitral regurgitation consistently results in a decrease in postoperative left ventricular (LV) ejection performance. This fall in ejection performance has been attributed, at least in part, to unfavorable loading conditions imposed by the elimination of the low-impedance pathway for LV emptying into the left atrium. In contrast to standard MVR in which the chordae tendineae are severed, however, MVR with chordal preservation (MVR-CP) does not usually decrease LV ejection performance despite similar removal of the low-impedance pathway. The purpose of the present study was to define the mechanisms responsible for this discordance in postoperative ejection performance between MVR with and without chordal preservation. METHODS AND RESULTS: Echocardiography and sphygmomanometer blood pressures were obtained in 15 patients with pure chronic mitral regurgitation before and 7-10 days after mitral valve surgery. These measurements were used to calculate ventricular volume, wall stress, and ejection fraction. Seven patients underwent MVR with chordal transection (MVR-CT), and eight patients underwent MVR CP. MVR-CT resulted in no postoperative change in LV end-diastolic volume, a significant increase in LV end-systolic volume, a significant increase in end systolic stress, from 89 +/- 9 to 111 +/- 12 g/cm2 (p < 0.05), and a significant decrease in ejection fraction, from 0.60 +/- 0.02 to 36 +/- 0.02 (p < 0.05). In contrast, patients who underwent MVR-CP had a significant decrease in LV end diastolic and end-systolic volumes. End-systolic wall stress actually fell from 95 +/- 6 to 66 +/- 6 g/cm2 (p < 0.05), and ejection fraction was unchanged (0.63 +/- 0.01 before and 0.61 +/- 0.02 after mitral valve surgery) instead of reduced. CONCLUSIONS: MVR-CT resulted in a decrease in ejection performance caused in part by an increase in end-systolic stress, which in turn increased end-systolic volume. Conversely, MVR-CP resulted in a smaller LV size, allowing a reduced end systolic stress and preservation of ejection performance despite closure of the low-impedance left atrial ejection pathway. PMID- 1451244 TI - Increased expression and regional differences of atrial myosin light chain 1 in human ventricles with old myocardial infarction. Analyses using two monoclonal antibodies. AB - BACKGROUND: This study was designed to examine the expression of atrial/fetal type myosin light chain 1 (ALC1) in human ventricles with old myocardial infarction and in control hearts. METHODS AND RESULTS: The expression of immunoreactive (ir) ALC1 was examined in the subendocardial and subepicardial myocardium of the infarcted and the noninfarcted regions in the left ventricles with old myocardial infarction (n = 12) and of the control left ventricles (n = 8). For the analysis, we prepared two monoclonal antibodies, KA1 and KB1, that were specific for only ALC1 and for both ALC1 and ventricular myosin light chain 1 (VLC1), respectively. The ir-ALC1 expression ratio [ALC1/(ALC1 + VLC1), %] of the subendocardial myocardium, determined densitometrically by Western blotting with KB1, was significantly higher in the infarcted region (11.4 +/- 7.3%) than in the noninfarcted region (4.7 +/- 2.3%, p < 0.001) and the control ventricle (1.0 +/- 1.5%, p < 0.0001). In the infarcted region, the subendocardial myocardium contained a significantly greater percentage of ir-ALC1 than the subepicardial myocardium (5.8 +/- 6.7%, p < 0.005). The ir-ALC1 expression ratio had a significant negative correlation with the value of tissue protein concentration (milligrams protein per gram wet weight). The immunohistochemical study with KA1 revealed that the surviving myocytes included in the infarcted region, especially in the ventricular aneurysm, expressed ir-ALC1 strongly in comparison with those in the noninfarcted or the control ventricles. CONCLUSIONS: These results demonstrate increased expression of ALC1 and the regional differences in the failing left ventricles with old myocardial infarction. We conclude that the reexpression of ALC1 in infarcted ventricles occurs as one of the regional responses to increased load and may be a useful biochemical marker for the appearance of fetal-type myocytes. PMID- 1451245 TI - Preoperative prediction of the outcome of coronary revascularization using positron emission tomography. AB - BACKGROUND: Previous assessments of myocardial viability using positron emission tomography (PET) relied on demonstration of glucose metabolism in hypoperfused asynergic segments using the glucose analogue [18F]2-fluoro-2-deoxyglucose (FDG). Recently, it was shown that myocardial viability could be assessed by calculating the water-perfusable tissue index (PTI) for the asynergic region. PTI represents the proportion of the myocardium that is capable of rapid transsarcolemmal exchange of water and thus perfusable by water. The aim of the present study was to assess myocardial viability by PET using PTI in patients undergoing coronary revascularization. METHODS AND RESULTS: Twelve patients with chronic coronary artery disease and previous myocardial infarction were studied. Analysis of transmission (tissue density) and 15O-labeled carbon monoxide (blood pool), and 15O-labeled water (myocardial blood flow [MBF]) emission PET data enabled the simultaneous quantification of MBF (ml.min-1.g perfusable tissue-1) and PTI (gram of perfusable tissue per gram of total anatomic tissue). In addition, PET imaging with FDG after 75-g oral glucose load was performed in eight patients. Preoperative echocardiography identified 33 hypocontractile and 26 control segments. Follow-up echocardiography performed 3 to 5 months later demonstrated 26 of 33 segments with improved wall motion (recovery) and seven of 33 segments without improvement (nonrecovery). MBF in the control segments (0.97 +/- 0.22 ml.min-1.g perfusable tissue-1) was significantly higher (p < 0.001) than in both the recovery (0.73 +/- 0.18 ml.min-1.g perfusable tissue-1) and the nonrecovery (0.45 +/- 0.11 ml.min-1.g perfusable tissue-1) segments. PTI in the recovery regions (0.99 +/- 0.15) was > or = 0.7 in all cases and slightly less than in control regions (1.10 +/- 0.15, p < 0.02). FDG uptake in these regions was 92 +/- 17% (n = 13) of the uptake in control segments with normal wall motion. In the nonrecovery group, PTI was 0.62 +/- 0.06 (p < 0.02 versus control and recovery) and always < 0.7. In the one patient in whom a comparison with metabolic imaging was made, FDG uptake was 46% of the uptake in a reference region with normal wall motion. CONCLUSIONS: These data showed that contractile recovery occurred only in segments where PTI was > or = 0.7, suggesting that > or = 70% of myocardial tissue in a given asynergic segment should be perfusable by water to enable contractile recovery. There was good agreement between the PTI and FDG methods for predicting improvements in regional wall motion after revascularization. Although further studies should be performed in a larger patient group, the preliminary results are promising and suggest that PTI may be a good predictor of contractile recovery after coronary revascularization. PMID- 1451246 TI - Preservation of atrioventricular nodal conduction during radiofrequency current catheter ablation of midseptal accessory pathways. AB - BACKGROUND: Septal accessory atrioventricular (AV) pathways may be located in close vicinity of the His bundle-AV nodal conduction system. Attempts at surgical or electrical interruption of these pathways may therefore result in impairment of normal AV conduction. This study focuses on a subset of septal pathways with an atrial insertion located inside the triangle of Koch. In this study, they were called "midseptal." METHODS AND RESULTS: Six patients with a midseptal accessory pathway (mean +/- SD age, 40 +/- 12 years; five with Wolff-Parkinson-White syndrome and one with a concealed accessory pathway) underwent attempts at ablation of their pathway using 500-kHz radiofrequency current applied to the atrial insertion of the accessory connection. Guided by the recording of accessory pathway activation potentials, the ablation catheter was positioned in all patients in an area bounded anteriorly by the tip electrode of the His bundle catheter and posteriorly by the coronary sinus ostium. All pathways were successfully ablated without the induction of complete heart block. First-degree AV conduction block occurred in one patient in whom a concealed accessory connection was located closer to the AV node than to the coronary sinus ostium. CONCLUSIONS: Radiofrequency current catheter ablation may be used effectively for midseptal accessory pathways and should be preferred in experienced centers as a safe alternative to surgical therapy. PMID- 1451247 TI - Natural history and patterns of recovery of contractile function in single left ventricle after Fontan operation. AB - BACKGROUND: Before the era of the Fontan procedure, the typical course of patients with single left ventricle (LV) consisted of heart failure and death during the second or third decade of life. Despite the advent of effective palliative therapy, ventricular dysfunction remains a significant clinical problem for these patients. METHODS AND RESULTS: To investigate the causes of ventricular dysfunction in these patients and to determine whether Fontan-type repair reverses deterioration of LV function, the ventricular dimensions, volume, shape, wall stress, and systolic function were determined by echocardiography in 84 patients 0.2-35 years old with double-inlet single LV or tricuspid atresia. Measurements were obtained in 67 patients after palliation (arterial shunt or pulmonary artery band) and in 47 patients a median of 4.4 years after a Glenn (n = 9) or a Fontan operation (n = 38). Before a Fontan procedure, ventricular volumes were 2 to 3 times normal. Ventricular afterload, assessed as circumferential and meridional end-systolic wall stress, became abnormal after 2 years of age. With age, LV shape changed progressively from ellipsoidal to spherical, as indicated by the decrease in long axis:short axis ratio from normal (1.9) toward unity. Concomitantly, the ratio of circumferential to meridional end systolic wall stress fell from 1.3 to unity, the ratio of a sphere at equilibrium. This age-related change in shape and load occurred in concert with progressive deterioration of LV systolic function and contractility. Aortic oxygen saturation, an indicator of pulmonary blood flow and therefore volume work in single-ventricle physiology, was inversely and independently correlated with contractility. In the group of patients in whom a Glenn or a Fontan operation was performed at < 10 years of age, ventricular dimensions, volumes, and wall stress diminished and LV function and contractility improved after surgery (p < 0.001). In patients undergoing surgery after 10 years of age, few had improvement of LV function after surgery. Postoperative ventricular function and contractility were inversely related to age at surgery and to aortic oxygen saturation measured before surgery. CONCLUSIONS: Although Fontan-type repair of single ventricle early in life is associated with reversal of the abnormal contractile mechanics associated with age and volume load, this capacity for recovery diminishes with age at surgery. PMID- 1451248 TI - Effect of baffle fenestration on outcome of the modified Fontan operation. AB - BACKGROUND: The "fenestrated Fontan" (surgical baffle fenestration followed by transcatheter test occlusion and permanent closure after postoperative recovery) was adopted in an effort to reduce perioperative mortality and morbidity. This study assesses the effect of baffle fenestration on outcome. METHODS AND RESULTS: Patients having a modified Fontan operation with a cavocaval baffle and cavopulmonary anastomosis were retrospectively selected for study. Those with baffle fenestration (n = 91) were compared with those without baffle fenestration (n = 56) with respect to preoperative risk factors, age, anatomy, surgical date, and presence or absence of a previous bidirectional cavopulmonary anastomosis. Outcome variables were failure (death or take-down) and duration of postoperative pleural effusions and hospitalization. Survival and clinical status after hospital discharge were ascertained. The two groups did not appear to differ with respect to age or anatomic diagnosis. Patients having baffle fenestration were at significantly greater preoperative risk by univariate and multivariate analysis (p < 0.01). Operative failure was low in both groups (11% without and 7% with baffle fenestration, p = NS). Durations of pleural effusions and hospitalization were significantly shorter with baffle fenestration (p < 0.01). Neither date of surgery nor a previous bidirectional cavopulmonary anastomosis appeared to contribute to improved outcome. Patients with baffle fenestration had lower postoperative systemic venous pressure (p < 0.01). There were no late deaths. Functional status in both groups is good (82% in New York Heart Association class I). CONCLUSIONS: Baffle fenestration is associated with low mortality, significantly less pleural effusion, and significantly shorter hospitalization among high-risk patients having a modified Fontan operation. PMID- 1451249 TI - Effects of pacing tachycardia and balloon valvuloplasty on pulmonary artery impedance and hydraulic power in mitral stenosis. AB - BACKGROUND: Mitral stenosis is characterized by progressive pulmonary hypertension and eventual right ventricular failure. However, the correlation between right ventricular failure and the level of pulmonary hypertension is poor, suggesting that factors other than those recognized from nonpulsatile hemodynamic parameters may contribute to impaired right ventricular performance in this condition. METHODS AND RESULTS: We studied 16 patients with severe mitral stenosis (mean valve area, 1.0 +/- 0.2 cm2) at supine rest and during pacing tachycardia using high-fidelity catheter recordings of pulmonary artery (PA) pressure and flow velocity. Pulmonary impedance spectra, wave reflection properties, and hydraulic power data were derived from Fourier analysis of signal averaged data. Pacing tachycardia (baseline heart rate, 81 +/- 11 beats per minute; pacing, 132 +/- 11 beats per minute) significantly raised pulmonary wedge and mean PA pressures. There was no change in pulmonary vascular resistance (209 +/- 144 to 232 +/- 164 dyne-sec/cm5) or PA characteristic impedance (62 +/- 25 to 55 +/- 28 dyne-sec/cm5). However, first harmonic impedance (Z1) significantly decreased (134 +/- 71 to 100 +/- 68 dyne-sec/cm5; p < 0.001). Accordingly, oscillatory and total dissipated hydraulic power per unit forward flow (WT/CO) fell during tachycardia (2.6 +/- 1.6 to 2.3 +/- 1.4 mW/ml.sec-1; p = 0.06) despite acute pulmonary hypertension. Reflected pressure waves returned earlier to the proximal PA, suggesting increased vessel stiffness. Immediately after percutaneous balloon mitral valvuloplasty (PBV) in eight of the patients, baseline and pacing data were again recorded. Compared with the pre-PBV baseline state, post-PBV resting data demonstrated no change in resistance or characteristic impedance, but there was a significant fall in Z1 (166 +/- 75 to 103 +/- 45 dyne-sec/cm5; p < 0.05) and in the magnitude of pulmonary wave reflections. WT/CO tended to decrease after PBV, and pacing after PBV produced a further decrease in WT/CO, again in association with lower Z1. CONCLUSIONS: These data demonstrate that 1) increased pulmonary characteristic impedance, although a feature of mitral stenosis, is not exacerbated by the acute effects of increased distending pressure; 2) pacing tachycardia in mitral stenosis causes little change in the pulmonary impedance spectrum except at low frequencies, where decreased impedance lowers power requirements per unit flow; and 3) relief of mitral stenosis produces immediate improvement in low-frequency impedance and in hydraulic power requirements. These findings suggest that although characteristic impedance may be a measure of the long-term effects of pulmonary hypertension on the pulmonary circulation, acute increases and decreases in PA pressure produce effects on right ventricular load that are best described in terms of the low frequency properties of the PA system. Improvement in low-frequency impedance diminishes hydraulic power requirements and thus reflects improved ventricular vascular coupling, irrespective of distending PA pressure. Efforts to treat or prevent right heart failure in the presence of pulmonary hypertension should take account of the potential benefit of changes in low-frequency impedance characteristics of the pulmonary vascular bed. PMID- 1451250 TI - Multivariate genetic analysis of blood pressure and body size. The Medical College of Virginia Twin Study. AB - BACKGROUND: In subjects of all ages, those who weigh the most often have the highest blood pressure. Thus, in epidemiological studies, weight is the most important correlate of blood pressure. Using the data from the Medical College of Virginia Twin Study, we asked these questions: 1) Do the same genetic paths that regulate body size also regulate systolic and diastolic blood pressure? 2) Are there distinct genetic pathways that regulate each of these variables? 3) Does environment play a major regulatory role? 4) Are the correlations among these variables mainly due to genetic or environmental effects? 5) Do genetic paths that regulate body size mediate the correlation between systolic blood pressure and diastolic blood pressure? METHODS AND RESULTS: We ascertained 253 Caucasian twin pairs living in the Commonwealth of Virginia. The average age was 11.2 +/- 0.2 years. We used multivariate path analyses to investigate the genetic relations among systolic blood pressure, diastolic blood pressure, and body size. We found that there was a highly significant genetic relation between systolic blood pressure and body size and between systolic and diastolic blood pressure. There are genetic paths that are shared within these two sets of variables, but in each case, the paths for each pair appear to be separate from one another. CONCLUSIONS: These analyses provide a method to partition correlation coefficients found in epidemiological studies into genetic and environmental components. The correlations found among these three variables are in large part due to these genetic relations. We found no genetic relation between diastolic blood pressure and body size. PMID- 1451251 TI - Augmented forearm vasoconstriction during dynamic exercise in healthy older men. AB - BACKGROUND: We tested the hypothesis that the nonactive limb vasoconstriction evoked during large-muscle dynamic exercise becomes augmented with aging in humans. METHODS AND RESULTS: Sixteen young control subjects (age, 26 +/- 1 year) and twelve older (65 +/- 1 year) healthy men with similar chronic physical activity levels were studied during supine leg cycling exercise. Both peak work load (1,100 +/- 60 versus 1,400 +/- 40 kpm/min) and peak O2 uptake (1.85 +/- 0.10 versus 2.38 +/- 0.07 l/min) were lower in the older men (p < 0.05). There were no differences in the two groups under conditions of quiet supine (basal) rest. During cycling for 5 minutes each at mild, moderate, and heavy submaximal intensities (approximately 45%, 65%, and 85% of peak O2 uptake), the increases in arterial blood pressure generally were similar in the young and older subjects; however, heart rate rose less in the older men (p < 0.05). Whole forearm blood flow (venous occlusion plethysmography) was lower and vascular resistance was higher (approximately 55-90%) in the older men at all loads (p < 0.05), but the steady-state forearm skin blood flow responses (laser Doppler velocimetry) were not different in the two groups. The increases in antecubital venous norepinephrine concentrations were greater in the older men at each work load (p < 0.05), although the plasma epinephrine responses were similar in the two groups. In other studies, 1) peak whole forearm reactive hyperemia and vascular conductance after sustained circulatory arrest (ischemia) were slightly (approximately 20%) but not significantly lower in the older men and 2) the forearm vasoconstrictor and plasma norepinephrine responses to a nonexercise sympathoexcitatory stimulus (limb immersion in ice water) tended to be blunted in the older men. CONCLUSIONS: During brief, submaximal, large-muscle dynamic exercise, healthy older men demonstrate augmented forearm vasoconstriction that is probably caused by greater constriction of skeletal muscle resistance vessels; this appears to be mediated, at least in part, by increased sympathetic outflow. These altered sympathetic vasoconstrictor adjustments do not represent a nonspecific hyperresponsiveness to acute stress with human aging. Finally, the regulation of arterial blood pressure appears to be normal in these healthy older men. PMID- 1451252 TI - Angiotensin converting enzyme inhibition restores cardiac and hormonal responses to volume overload in patients with dilated cardiomyopathy and mild heart failure. AB - BACKGROUND: Angiotensin converting enzyme (ACE) inhibition exerts a favorable effect on the response to exercise in heart failure. This study was planned to define the influence of ACE inhibition on the adaptation to volume overload. METHODS AND RESULTS: We studied the hemodynamic, hormonal, and renal responses to acute volume expansion (sodium chloride, 0.9%, 0.25 ml.kg-1.min-1 for 2 hours) in patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (New York Heart Association class I or II, ejection fraction < or = 50%). The patients were studied without any pretreatment (n = 14) or after 1 week of treatment with the oral ACE inhibitor quinapril at a dosage of 10 mg/day (n = 11). Seven patients were studied during constant intravenous infusion with nitroglycerin (0.1 micrograms.kg-1.min-1). The study groups had similar hemodynamic and clinical characteristics and hormonal profile at baseline evaluation. In the untreated patients, volume expansion did not increase left ventricular end-diastolic volume measured by echocardiography and was associated with a reduction in ejection fraction (p < 0.05) and with a paradoxical increase in forearm vascular resistance (p < 0.05) estimated by plethysmography. In addition, plasma atrial natriuretic factor did not change, and plasma norepinephrine was increased by saline loading. In contrast, in the patients treated with quinapril, volume expansion induced an increase of both left ventricular volumes (p < 0.001) without changing ejection fraction and reduced forearm vascular resistance (p < 0.05). In addition, in this group, plasma atrial natriuretic factor levels increased (p < 0.05) and plasma norepinephrine did not change during volume overload. During nitroglycerin infusion, volume expansion was associated with peripheral vasodilatation, increases of left ventricular volumes, and no change in ejection fraction. In this group, however, plasma atrial natriuretic factor levels did not change in response to volume overload. CONCLUSIONS: We conclude that pretreatment with the ACE inhibitor quinapril significantly improves compromised responses to acute isotonic volume overload in patients with dilated cardiomyopathy and mild heart failure. The favorable influence of ACE inhibition on cardiovascular and hormonal responses to volume expansion seems to be related to the cardiac unloading produced by this treatment. PMID- 1451253 TI - 31P magnetic resonance spectroscopy in dilated cardiomyopathy and coronary artery disease. Altered cardiac high-energy phosphate metabolism in heart failure. AB - BACKGROUND: The purpose of this work was to further define the value of cardiac 31P magnetic resonance (MR) spectroscopy for patients with coronary artery disease and dilated cardiomyopathy. METHODS AND RESULTS: Blood-corrected and T1 corrected 31P MR spectra of anteroseptal myocardium were obtained at rest using image-selected in vivo spectroscopy localization, a selected volume of 85 +/- 12 cm3, and a field strength of 1.5 T. Nineteen volunteers had a creatine phosphate (CP)/ATP ratio of 1.95 +/- 0.45 (mean +/- SD) and a PDE/ATP ratio of 1.06 +/- 0.53; in four patients with left anterior descending coronary artery (LAD) stenosis, six patients with chronic anterior wall infarction, and four patients with chronic posterior wall infarction, CP/ATP and phosphodiester (PDE)/ATP ratios did not differ from those in volunteers. Twenty-five measurements of 19 patients with dilated cardiomyopathy yielded a CP/ATP of 1.78 +/- 0.51 and a PDE/ATP of 0.98 +/- 0.56 (p = NS versus volunteers). When these patients were grouped according to the severity of heart failure, however, CP/ATP was 1.94 +/- 0.43 in mild (p = NS versus volunteers) and 1.44 +/- 0.52 in severe DCM (p < 0.05), respectively. No correlation was found between CP/ATP and left ventricular ejection fraction or fractional shortening, but correlation of CP/ATP with the New York Heart Association (NYHA) class was significant (r = 0.60, p < 0.005). Six patients with dilated cardiomyopathy were studied repeatedly before and after 12 +/- 6 weeks of drug treatment leading to clinical recompensation with improvement of the NYHA status by 0.8 +/- 0.3 classes. Concomitantly, CP/ATP increased from 1.51 +/- 0.32 to 2.15 +/- 0.27 (p < 0.01), whereas PDE/ATP did not change significantly. CONCLUSIONS: Cardiac high-energy phosphate metabolism at rest is normal in LAD stenosis and chronic myocardial infarction in the absence of heart failure. The CP/ATP ratio has low specificity for the diagnosis of dilated cardiomyopathy. However, CP/ATP correlated with the clinical severity of heart failure and may improve during clinical recompensation. PMID- 1451254 TI - Cross-bridge dynamics in human ventricular myocardium. Regulation of contractility in the failing heart. AB - BACKGROUND: To investigate whether altered cross-bridge kinetics contribute to the contractile abnormalities observed in heart failure, we determined the mechanical properties of cardiac muscles from control and myopathic hearts. METHODS AND RESULTS: Muscle fibers from normal (n = 5) and dilated cardiomyopathy (n = 6) hearts were obtained and chemically skinned with saponin. The muscles were then maximally activated at saturating calcium concentrations. Unloaded shortening velocities (V0) were determined in both groups. V0 in control was 0.72 +/- 0.09 Lmax/sec, whereas in myopathic muscles, V0 was 0.41 +/- 0.06 Lmax/sec at 22 degrees C. The muscles were also sinusoidally oscillated at frequencies ranging between 0.01 and 100 Hz. The dynamic stiffness of the muscles was calculated from the ratio of force response amplitude to length oscillation amplitude. At low frequencies (< 0.2 Hz) the stiffness was constant but was larger in myopathic muscles. In the range of 0.2-1 Hz, there was a drop in the magnitude of dynamic stiffness to approximately one quarter of the low-frequency baseline. This range reflects cross-bridge turnover kinetics. In control muscles, the frequency of minimum stiffness was 0.78 +/- 0.06 Hz, whereas it was 0.42 +/- 0.07 Hz in myopathic muscles. At higher frequencies, the dynamic stiffness increased and reached a plateau at 30 Hz. There were no differences in the plateau reached between control and myopathic muscles. CONCLUSIONS: Because myopathic hearts have a markedly diminished energy reserve, the slowing of the cross-bridge cycling rate plays an important adaptational role in the observed contractility changes in human heart failure. Although the potential to generate maximal Ca(2+)-activated force is similar in normal and myopathic hearts, alterations in contractile protein composition could explain the diminished cross bridge cycling rate in failing hearts. PMID- 1451255 TI - The importance of acute luminal diameter in determining restenosis after coronary atherectomy or stenting. AB - BACKGROUND: We evaluated native coronary arteries treated by directional coronary atherectomy or balloon-expandable stent placement in an effort to derive a quantitative geometric model relating the luminal diameter immediately after intervention to that present 6 months later. The minimal luminal diameter of each lesion was measured before and immediately after intervention in 102 single Palmaz-Schatz stents and 134 directional atherectomies, 192 (81%) of which had repeat angiographic measurement of minimal luminal diameter 6 months after the intervention. The immediate enlargement in luminal diameter produced by the intervention (acute gain) and the subsequent reduction in luminal diameter from the time of intervention to 6 months of follow-up (late loss) were calculated. METHODS AND RESULTS: Luminal diameter increased from 0.69 +/- 0.40 mm to 3.11 +/- 0.64 mm (acute gain, 2.41 +/- 0.64 mm) after intervention, providing an immediate postprocedure residual stenosis of 1 +/- 14% relative to a reference diameter of 3.13 +/- 0.65 mm. At 6-month follow-up, the late luminal diameter was 1.97 +/- 0.92 mm (late loss, 1.13 +/- 0.89 mm), yielding a late diameter stenosis of 36 +/ 26%. The restenosis rate (according to the traditional definition of diameter stenosis > or = 50%) was 30%. Multivariable analysis demonstrated that late luminal diameter (p = 0.02), late percent stenosis (p = 0.04), and restenosis (according to a > 50% definition, p = 0.04) were each strongly associated with the luminal diameter present immediately after the procedure. Whereas late luminal diameter was also influenced by reference artery size and the vessel treated (left anterior descending versus right coronary artery), reference vessel size was rejected by the multivariable models of late percent stenosis and binary restenosis after they were adjusted for the effect of postprocedure luminal diameter. Once adjusted for postprocedure luminal diameter, neither late luminal diameter nor late loss was found to be independently determined by which device was used (atherectomy versus stents). Rather, late loss was determined independently by the immediate postprocedure luminal diameter (p = 0.005) and the postprocedure percent stenosis (p = 0.02). Although late loss thus increased with acute gain, the net beneficial effect of increased acute gain was maintained: Late loss was only a fraction (0.47) of acute gain, so the ability of a larger postprocedure luminal diameter to reduce the probability of subsequent restenosis was preserved. CONCLUSIONS: This quantitative model demonstrates that the late coronary lumen diameter and the probability of restenosis after Palmaz-Schatz stenting or directional atherectomy are influenced strongly by the lumen diameter present immediately after the procedure rather than by the specific device used. Although the influence of a larger acute result on reduced restenosis appears to be well established in this treatment population, the interplay among the multiple other biological influences on restenosis limits the ability to predict the probability of restenosis for the individual patient based on a large acute result alone. Future studies of restenosis, however, can further refine this multivariable quantitative model by adjusting for the effects of other clinical variables, mechanical interventions, or drug therapies in addition to the clear effect of postprocedure luminal diameter. PMID- 1451256 TI - Restenosis after placement of Palmaz-Schatz stents in native coronary arteries. Initial results of a multicenter experience. AB - BACKGROUND: Several metallic intracoronary stents are currently undergoing preliminary evaluation to ascertain potential benefit as means to reduce the 30 40% incidence of restenosis after balloon angioplasty. METHODS AND RESULTS: To determine the incidence and correlates of restenosis after placement of Palmaz Schatz stents in native coronary arteries in the first group of patients selected for this procedure, clinical and quantitative angiographic data from 206 consecutive patients (221 stenoses) with successful stent placement (diameter stenosis < 50%) were analyzed. Six patients (2.9%) had thrombosis-mediated stent closure within 1 month after stent placement and were excluded from long-term angiographic follow-up. One hundred eighty-one (91%) of the remaining 200 patients had angiography at 5.8 +/- 2.1 months. Patients with and without follow up did not differ in any baseline characteristic; in particular, history of restenosis at the site stented (73% versus 65%), placement of multiple overlapping stents (17% versus 20%), and mean poststent diameter stenosis (16 +/- 12% versus 14 +/- 12%). The overall incidence of restenosis (diameter stenosis > or = 50% at follow-up) in this group at high risk for restenosis was 36% (95% confidence interval, 29-43%) on a per-stenosis basis. The incidence of restenosis when a single stent was placed was 30% (95% confidence interval, 23-37%). Risk was dependent upon a history of restenosis (present versus absent 36% versus 16%, p = 0.02) and upon whether or not a poststent stenosis < or = 0% was achieved (6% versus 33%, p = 0.02). When multiple overlapping stents were placed, restenosis occurred at 64% of sites, and placement of multiple stents was discouraged during the later phases of this study as these results became apparent. CONCLUSIONS: Although multiple stents appear to yield a poor long-term result, placement of single stents may offer a benefit compared with standard coronary angioplasty, particularly if an excellent angiographic result can be obtained in patients without prior restenosis. Further randomized trials in such patients are needed. PMID- 1451257 TI - How does angioplasty work? Serial analysis of human iliac arteries using intravascular ultrasound. AB - BACKGROUND: Previous studies regarding the mechanism by which balloon angioplasty increases luminal patency have generally used animal models or postmortem specimens from occasional fatal cases of angioplasty performed in human patients. In either case, conclusions regarding participatory mechanisms have relied exclusively on nonserial, postangioplasty histopathological examination. METHODS AND RESULTS: In the present study, intravascular ultrasound examination was performed before and after balloon angioplasty in 40 consecutive patients with iliac artery stenoses. The areas of the arterial wall, plaque, lumen, and areas resulting from angioplasty-induced plaque fractures were measured immediately after angioplasty in vivo and compared with findings recorded immediately before angioplasty. Angioplasty increased luminal cross-sectional area (CSA) from 11.5 +/- 0.6 mm2 before angioplasty to 25.4 +/- 1.2 mm2 after angioplasty (p = 0.0001). CSA of the portion of the postangioplasty neolumen contained within angioplasty-induced plaque fractures measured 10.0 +/- 0.8 mm2; the neolumen excluding the area contributed by these plaque fractures measured 15.4 +/- 0.8 mm2. Thus, the area contained within plaque fractures accounted for 10.0 mm2 (71.9%) of the 13.9-mm2 increase in luminal CSA after angioplasty. Analysis of CSA occupied by atherosclerotic plaque disclosed that plaque CSA decreased from 33.8 +/- 1.8 mm2 before angioplasty to 22.5 +/- 1.5 mm2 after angioplasty (p = 0.0001). Plaque CSA was thus reduced ("compressed") by 11.3 +/- 1.1 mm2. Total artery CSA increased ("stretched") slightly from 45.3 +/- 2.6 mm2 before angioplasty to 47.8 +/- 2.0 mm2 after angioplasty (p = 0.0025). CONCLUSIONS: In vivo analysis of iliac stenoses by intravascular ultrasound immediately before and after angioplasty demonstrates that plaque fractures and "compression" of atherosclerotic plaque are the principal factors responsible for increased luminal patency resulting from balloon angioplasty. "Stretching" of the arterial wall provides an additional, but minor, contribution. PMID- 1451258 TI - Endothelial dysfunction in patients with chest pain and normal coronary arteries. AB - BACKGROUND: A subgroup of patients with chest pain and angiographically normal epicardial coronary arteries have reduced dilator response to metabolic or pharmacological stimuli, but the mechanisms responsible for this reduced dilator response are unknown. In this study, we have investigated whether microvascular endothelial dysfunction is a cause of the observed reduced vasodilator reserve. METHODS AND RESULTS: The functional response of the microvasculature was studied with rapid atrial pacing at 150 beats per minute. Fifty-one patients, 20 hypertensive and 31 normotensive, with chest pain and normal epicardial coronary arteries (< 10% stenosis) were studied. Endothelial function was tested with incremental infusions of acetylcholine to achieve estimated intracoronary concentrations ranging from 10(-7) M to 10(-5) M. Endothelium-independent smooth muscle vasomotion was measured using intracoronary sodium nitroprusside. Endothelial dysfunction of epicardial coronary arteries, demonstrated as severe (> 50%) constriction with < 10(-5) M acetylcholine concentration, was evident in five patients (10%). In the remaining 46 patients, coronary blood flow increased with acetylcholine (mean, 78 +/- 43%) and atrial pacing (mean, 51 +/- 37%), and coronary vascular resistance decreased by 35 +/- 16% and 29 +/- 14%, respectively, but the responses were heterogeneous. There was a correlation between the coronary resistance change with acetylcholine and the change with atrial pacing: r = 0.68, p < 0.001 in these 46 patients. Thus, patients with depressed dilation with atrial pacing had reduced endothelium-dependent dilation with acetylcholine, and vice versa. However, the microvascular dilation caused by sodium nitroprusside was not significantly different between patients with and those without reduced dilation with atrial pacing, indicating that the vasodilator defect was not caused by smooth muscle dysfunction. There were no differences in the vasodilator responses with atrial pacing, acetylcholine, or nitroprusside between normotensive and hypertensive patients. Multivariate regression analysis was performed to determine whether age, sex, serum cholesterol level, hypertension, presence of mild epicardial vessel atherosclerosis, resting left ventricular function, change in left ventricular ejection fraction with exercise, vasodilation with acetylcholine, and vasodilation with sodium nitroprusside were independently related to the vasodilator response to atrial pacing. Only the change in coronary vascular resistance with acetylcholine was independently correlated with the change in resistance with atrial pacing: R2 = 0.46, p < 0.0001. CONCLUSIONS: Patients with chest pain, normal epicardial coronary arteries, and reduced vasodilation in response to atrial pacing appear to have associated endothelial dysfunction of the coronary microvasculature. Thus, microvascular endothelial dysfunction may contribute to the reduced vasodilator reserve with atrial pacing and anginal chest pain in these patients. PMID- 1451259 TI - Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart. AB - BACKGROUND: To determine the mechanisms of ventricular tachycardia (VT) in humans, three-dimensional intraoperative mapping of up to 156 intramural sites was performed in 13 patients with healed myocardial infarction and refractory VT. METHODS AND RESULTS: Mapping was of sufficient density to define the mechanism of 10 VTs in eight patients. In five of 10 cases, sustained VT was initiated in the subendocardium or epicardium by intramural reentry with marked conduction delay as well as functional and anatomic block most prominent in the subendocardium and midmyocardium. The initiating beats of reentrant VT induced by programmed electrical stimulation arose in the endocardium or midmyocardium by progressive slowing of conduction leading to unidirectional block. Multiple simultaneous reentrant circuits can be present. In contrast, five of the 10 sustained VTs were initiated by a focal mechanism as defined by the absence of electrical activity between the termination of one beat and the initiation of the next despite the presence of multiple intervening intramural electrode recording sites. Comparisons of the mapping data with results of histopathological analysis of tissue demonstrated that the location of infarction as well as that of adjacent fibrotic muscle determined sites of both fixed and functional conduction block during macroreentrant VT and that slowing of conduction occurred in a direction transverse rather than longitudinal to fiber orientation. CONCLUSIONS: Both intramural reentry and a focal mechanism underlie sustained VT in patients with healed myocardial infarction. PMID- 1451260 TI - Contribution of myocardium responsible for ventricular tachycardia to abnormalities detected by analysis of signal-averaged ECGs. AB - BACKGROUND: Current methods of signal-averaged ECG analysis interrogate the terminal 40 msec of the QRS complex and/or the ST segment and have a low positive predictive accuracy for detecting vulnerability to sustained ventricular tachycardia (VT). The extent to which abnormalities detected during these ECG intervals are generated by myocardial tissue responsible for VT has not been well defined. The purpose of this study was to determine when, during sinus rhythm, myocardium responsible for VT is activated. METHODS AND RESULTS: Three dimensional ventricular activation maps were analyzed during sinus rhythm and during 10 VTs in eight patients with healed myocardial infarctions undergoing arrhythmia surgery for sustained monomorphic VT. The mechanism of VT was focal in five instances and macroreentrant in five. During sinus beats, myocardium responsible for all focal VTs activated 43 +/- 38 msec before the onset of the terminal 40-msec interval of the QRS complex. During sinus rhythm, activation of the myocardium critical to macroreentrant VT began 72 +/- 13 msec before the onset of the terminal QRS interval and in only three instances extended 2-25 msec into the terminal 40 msec of the QRS complex. Electrograms recorded during the ST segment represented late activation of epicardial sites overlying zones of infarction that were temporally and spatially remote from tissue critical to VT. CONCLUSIONS: Current methods of signal-averaged ECG analysis limiting interrogation to the terminal QRS/ST segment exclude detection of > 95% of the signals generated by myocardium responsible for sustained VT. These results establish a pathophysiological basis for expanding signal-averaged ECG analysis to include more of the cardiac cycle. PMID- 1451261 TI - Transcatheter closure of patent foramen ovale after presumed paradoxical embolism. AB - BACKGROUND: Many have proposed a relation between presence of a patent foramen ovale, with or without atrial septal aneurysm, and cryptogenic stroke. The effect of foramen ovale closure on the risk for subsequent strokes is unknown. METHODS AND RESULTS: Transcatheter closure of a patent foramen ovale was undertaken in 36 patients with known right-to-left atrial shunting and presumed paradoxical emboli (31 strokes, 25 transient neurological events, four systemic arterial emboli, and two brain abscesses). Individual patients had between one and four such events. None had a left heart or carotid source of embolism; 31 of 35 had no known risk factors for stroke. Events occurred in 12 patients while they were taking warfarin. At cardiac catheterization, patent foramina ovalia were significantly larger than predicted for age in 67% of the patients. Implantation of a double umbrella device in the patent foramen ovale was achieved in all without serious procedural complications. Of 34 who have returned for follow-up, one has a residual atrial communication that may be clinically important, five had trivial leaks, and 28 have complete closure. There have been no strokes during a mean follow-up of 8.4 months. CONCLUSIONS: Transcatheter closure of a patent foramen ovale can be accomplished with little morbidity and may reduce the risk of recurrence. Further investigations directed toward identifying the population at risk and assessing the effect of intervention are warranted. PMID- 1451262 TI - Parallel cardiac and vascular adaptation in hypertension. AB - BACKGROUND: Although vascular damage in the noncoronary circulation is a major cause of complications in hypertension, relatively little is known of the in vivo geometry and function of the arterial circulation in patients with uncomplicated hypertension or of their relation to left ventricular hypertrophy, a marker of enhanced risk of cardiovascular complications. METHODS AND RESULTS: Wall thickness and internal diameter of the common carotid artery and the presence of atherosclerosis within the extracranial carotid arteries were determined by ultrasound in 43 asymptomatic hypertensive patients and 43 normotensive subjects matched for sex, age, and body size. Vascular stiffness was estimated from simultaneous superimposed carotid pressure waveforms obtained with an external solid-state transducer. Left ventricular size and function were determined echocardiographically. Compared with normal subjects, hypertensive patients had greater left ventricular absolute and relative wall thicknesses, left ventricular mass, and carotid absolute and relative wall thicknesses (p < 0.005). Carotid intimal-medial thickness exceeded the 95th percentile of normal values in 28% of hypertensive patients (p < 0.01). Carotid atherosclerosis was equally prevalent within the two blood pressure groups and was associated with older age, larger left ventricular and carotid wall thicknesses, and carotid diameter. Despite similar carotid pulse pressures, vascular stiffness was significantly increased in the hypertensive patients. Among the population as a whole, significant relations existed between cardiac and vascular wall thicknesses and internal dimensions. In multivariate analyses, these relations were statistically independent of age and blood pressure. CONCLUSIONS: The present study documents the presence of geometric and functional changes within the common carotid artery in uncomplicated hypertension that parallel findings within the left ventricle. The potential contribution of these changes to the cardiovascular complications of hypertension, particularly in the setting of left ventricular hypertrophy, is unknown. PMID- 1451263 TI - Evaluation of left ventricular segmental wall motion in hypertrophic cardiomyopathy with myocardial tagging. AB - BACKGROUND: Segmental wall motion was assessed noninvasively in eight patients with hypertrophic cardiomyopathy and six healthy volunteers by magnetic resonance myocardial tagging. METHODS AND RESULTS: Localization scans were performed for determination of the true short-axis views of the left ventricle (double angulated view). Spatial modulation of magnetization was used to produce a rectangular grid of landmarks. Distortion of the grid was assessed at end diastole, mid systole, and end systole with multiphase gradient echoes. Image sets were acquired at three different planes, namely, the base, the equator, and the apex. Quantitative evaluation was carried out by computer-assisted image analysis. Each individual grid crossing point was identified automatically and the displacement calculated. A polar coordinate system with the center of gravity as motion reference point was chosen to assess fractional rotation and radial displacement at the endocardial, midwall, and epicardial layers of the septal, anterior, posterior, and inferior regions. A wringing motion of the left ventricle with a clockwise rotation of 5.0 +/- 2.4 degrees at the base and a counterclockwise rotation of -9.6 +/- 2.9 degrees at the apex was observed in control subjects. An equal rotation of 5.0 +/- 2.5 degrees at the base and a slightly reduced rotation of -7.3 +/- 5.2 degrees at the apex was found in patients with hypertrophic cardiomyopathy. A transmural gradient in fractional rotation and radial displacement was observed, with the highest values in the endocardial layer. Rotation in patients with hypertrophic cardiomyopathy was significantly less than in normal volunteers in the posterior region of the equatorial and apical planes. Furthermore, radial displacement was significantly reduced in the septum and inferior wall. In the anterior and posterior wall segments, a reduction of the radial displacement was observed only in the epicardium and midwall layers. CONCLUSIONS: Magnetic resonance myocardial tagging allows the noninvasive assessment of regional wall motion. Both in normal volunteers and in patients with hypertrophic cardiomyopathies, cardiac motion occurs in a complex mode, with the base and the apex rotating in opposite directions and the equatorial plane as a transitional zone (wringing motion). A reduced cardiac rotation can be observed in patients with hypertrophic cardiomyopathy mainly in the posterior region, whereas a reduced radial displacement is found in the inferior septal zone. PMID- 1451264 TI - Control of sympathetic nerve activity by vagal mechanoreflexes is blunted in heart failure. AB - BACKGROUND: Previous studies have documented abnormalities of arterial baroreflexes in animals and patients with congestive heart failure. This study determined whether cardiopulmonary reflex control of sympathetic nerve activity was abnormal in a canine model of low-output heart failure induced by rapid ventricular pacing. METHODS AND RESULTS: We stimulated mechanoreceptors throughout the cardiopulmonary region by volume expansion and left atrial mechanoreceptors selectively by inflating small balloons at the junctions of the pulmonary veins and left atrium. Responses of renal sympathetic nerve activity and left atrial and systemic arterial pressures were recorded. In the control group, 15% volume expansion raised left atrial pressure 3.5 +/- 0.8 mm Hg and resulted in a 70 +/- 8% reduction in renal nerve activity. In the heart failure group, 15% volume expansion resulted in a 6.8 +/- 3.0 mm Hg rise in left atrial pressure with only a 16 +/- 20% reduction in renal nerve activity (p < 0.01). When volume expansion was performed after pretreatment with hemorrhage to lower left atrial pressure to the normal range in the heart failure group, the markedly attenuated response in the heart failure group persisted. After vagotomy, volume expansion elicited no change in renal nerve activity. Inflation of the atrial balloons caused a 28 +/- 9% reduction in renal sympathetic nerve activity and a 13 +/- 4 mm Hg decrease in arterial pressure in the control group. Renal nerve activity (-5 +/- 3%) and mean arterial pressure (-1 +/- 1 mm Hg) did not change with balloon inflation in the heart failure group. CONCLUSIONS: We conclude that dogs with low-output heart failure exhibit marked attenuation of cardiopulmonary mechanoreflex control of sympathetic nerve activity. This attenuated response is mediated via cardiac vagal afferent fibers and is due to either abnormalities in cardiopulmonary baroreceptors or abnormalities in the central nervous system. PMID- 1451265 TI - Myocardial cell hypertrophy after myocardial infarction with reperfusion in dogs. AB - BACKGROUND: The potential role of myocardial cell hypertrophy in the ischemic zone in the mechanism of late recovery of regional contractile function after myocardial infarction followed by reperfusion has not been examined. METHODS AND RESULTS: Eight chronically instrumented, conscious dogs were subjected to 90-120 minutes of circumflex coronary artery occlusion followed by reperfusion. The thickness and function of the anterior (AT) and posterior (PT) walls was measured by ultrasonic gauges at control, during occlusion, and after reperfusion. After 3 weeks, cross-sectional areas of surviving cells were determined from subepicardial (epi), midwall (mid), and subendocardial (endo) regions in six dogs and compared with those from six animals without infarction, including three sham operated control dogs. PT systolic wall thickening showed dyskinesia during occlusion but recovered after reperfusion to 48% of control at 1 week and 67% at 3 weeks. End-diastolic thickness of the PT wall increased markedly after reperfusion, but AT and PT walls were only slightly thicker (p = NS) than in control dogs at 3 weeks. Cross-sectional areas of reperfused dogs in the infarct region averaged 279 (PTepi), 291 (PTmid), and 317 microns 2 (PTendo) and were significantly larger than in control animals (237 [PTepi], 241 [PTmid], and 233 microns 2 [PTendo]). PT cell areas were significantly larger than AT cells, ENDO cell areas were larger than EPI cells (both p < 0.05), and ENDO cells of the AT wall were larger than those of noninfarcted dogs (p < 0.05). CONCLUSIONS: In dogs with myocardial infarction followed by reperfusion, the cross-sectional areas of cells in the infarcted PT wall were larger than those in the noninfarcted AT wall, and within both the infarcted and noninfarcted zones, cell areas were larger in the endocardial than the epicardial region. In all regions of the infarcted wall and in the ENDO region of the noninfarcted wall, cell areas were generally larger than those of control dogs without infarction, and the control dogs showed no transmural differences in cell areas. The mechanisms responsible for this significant remodeling of the reperfused infarcted zone, which involves myocardial cellular hypertrophy, are unknown, but it is possible that hypertrophy of surviving regions of the infarcted wall played a role in the late recovery of regional function that accompanied this hypertrophic response. PMID- 1451266 TI - Effects of calcium and EMD-53998 on oxygen consumption in isolated canine hearts. AB - BACKGROUND: Most positive inotropic agents increase cardiac contractility by increasing the amount of Ca2+ cycled with each beat. The additional amount of oxygen that is consumed by the heart to cycle this additional Ca2+ is believed to reduce myocardial efficiency. On the other hand, it has been suggested that the agent EMD-53998 increases the Ca2+ sensitivity of the contractile proteins without affecting the intracellular Ca2+ transient in cardiac muscle. Therefore, application of this agent may increase cardiac contractility without decreasing myocardial efficiency. The purpose of the present study was to test this hypothesis. METHODS AND RESULTS: We measured myocardial oxygen consumption (MVO2) in six isolated, isovolumically beating blood-perfused canine hearts. The hearts were paced at 120 beats per minute. Contractility was varied in each heart by infusion of either CaCl2 or EMD-53998. With infusion of either agent, MVO2 was a linearly proportional function of contractility. No significant difference between CaCl2 and EMD-53998 could be detected in the interrelation between contractility and MVO2. CONCLUSIONS: We conclude that the "calcium-sensitizing agent" EMD-53998 is a potent positive inotropic agent in the isolated, blood perfused canine heart. However, EMD-53998 does not provide an energetic advantage over currently used positive inotropic agents. PMID- 1451267 TI - Diastolic vibration improves systolic function in cases of incomplete relaxation. AB - BACKGROUND: Incomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved. METHODS AND RESULTS: Using 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r = 0.82), the assumed index of severity of incomplete relaxation. CONCLUSIONS: These results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism. PMID- 1451268 TI - Myocardial uptake of 111In monoclonal antimyosin Fab in detecting doxorubicin cardiotoxicity in rats. Morphological and hemodynamic findings. AB - BACKGROUND: The therapeutic value of doxorubicin (DOX) is limited by its cardiotoxicity, which is dose dependent. To improve the detection of such myocardial damage, this study was designed to determine whether the 111In antimyosin antibody Fab could serve as a marker for cardiotoxicity in treated versus control rats on the basis of comparative morphological and hemodynamic findings. METHODS AND RESULTS: DOX was administered by intravenous injection to rats at a dose of 3 mg.kg-1.week-1 for 5 weeks. Three weeks after the final injection, an intravenous dose of 111In antimyosin, 740 kBq (20 microCi), was administered, and tissue distribution of the radioisotope (percent kilogram dose per gram) was assessed in 48 hours. Myocardial uptake of radioactivity by both ventricles was more prominent in the DOX-treated rats than in control rats (p < 0.001). The heart-to-blood and heart-to-lung uptake ratios were markedly higher in the treated rats than in controls (p < 0.001). As the severity of the myocardial damage increased, there was a progressive increase in myocardial uptake. There was a strong correlation between the severity of myocardial damage and the ventricular end-diastolic pressure (r = 0.84 and r = 0.83 in the left and right ventricles, respectively). On microscopic immunoautoradiography of the DOX treated heart, there was a specific immunolocalization of the radiotracer in the injured myocytes but no radioactivity in the control myocytes. CONCLUSIONS: 111In antimyosin antibody appears to be a useful immunoradiotracer in detecting cardiac damage induced by DOX administration and in assessing the severity of cardiotoxicity. These data reinforce the clinical observation that myocardial imaging using 111In antimyosin Fab is able to provide information to guide the course of patients receiving DOX treatment. PMID- 1451269 TI - Effects of calcium channel blockers on calcium uptake in rat aortic valve allografts. AB - BACKGROUND: The life span of human aortic valve allografts is finite, and many fail because of cusp rupture or calcification. Subcellular changes occurring in aortic valves in response to transplantation include the uptake of calcium. This study uses a heterotropic rat aortic valve transplant model to determine whether the calcium channel blockers diltiazem and verapamil might attenuate leaflet calcification. METHODS AND RESULTS: The 60 rats studied were divided into the following groups: 1) control: valves from normal, unoperated F1 generation of Lewis and Brown Norway cross (LBNF1) rats; 2) control: valves from syngeneic transplant combinations (Lewis/Lewis); 3) control: valves from allogeneic transplant combinations (LBNF1/Lewis, donor/recipient); 4) experimental: valves from allogeneic strain combinations treated with 30 mg/kg per day diltiazem; 5) experimental: valves from allogeneic strain combinations treated with 30 mg/kg per day verapamil. Drugs or saline (controls) were administered with osmotic pumps placed subcutaneously 2 days before transplantation. Animals were killed 3 weeks later, and the valves were harvested and prepared for calcium analysis. Energy-dispersive x-ray microanalysis was used to measure the calcium in a section of one leaflet from each valve studied. Paired t tests showed that allograft valves treated with diltiazem or verapamil contained significantly less calcium than allograft controls treated with saline (p < 0.001). When all five groups were subjected to one-way ANOVA, the valves in the allograft control group contained significantly more calcium than all other groups. All other groups were not different from each other. CONCLUSIONS: The calcium channel blockers verapamil and diltiazem were effective in preventing early calcification that occurs in aortic valves after transplantation. Thus, these agents might play a role in prolonging the life of human aortic valve allografts. PMID- 1451270 TI - Effects of vagal stimulation on cesium-induced early afterdepolarizations and ventricular arrhythmias in rabbits. AB - BACKGROUND: Previous evidence has shown that increased sympathetic tone enhances the cesium chloride (Cs)-induced early afterdepolarizations (EADs) and ventricular tachycardias (VTs). METHODS AND RESULTS: We assessed the effects of vagal stimulation on Cs-induced EADs and ventricular arrhythmias in the rabbit heart. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with surface ECG. Two protocols were used: 1) While in their intrinsic sinus rhythm, 11 rabbits were given three intravenous Cs injections (1 mM/kg) 20 minutes apart, and the effects of vagal stimulation on the ventricular arrhythmias thus induced were examined. 2) Under constant atrial pacing (cycle length, 250 msec), EAD amplitude was measured after Cs injection (1 mM/kg) without (five rabbits, control group) or with (four rabbits, vagal stimulation group) vagal stimulation. We observed the following. 1) Cs produced EADs and VTs of polymorphic (PVT) and monomorphic (MVT) types. During PVT, the take-off potential of repetitive premature action potentials in MAP recordings was about the same as the peak level of EADs, and during MVT, the take-off potential was the level of full repolarization. Vagal stimulation suppressed PVT but not MVT. Vagal stimulation after spontaneous termination of MVT restarted MVT of the same morphology at a rate much slower than the preceding sinus rate. 2) EAD amplitude was significantly smaller in the vagal stimulation group than in the control group. CONCLUSIONS: The results suggest that PVT originated from triggering by EADs, whereas MVT was of different origin, and that vagal stimulation suppressed PVT by decreasing the amplitude of EADs. PMID- 1451271 TI - Combination of inhibition of thrombin and blockade of thromboxane A2 synthetase and receptors enhances thrombolysis and delays reocclusion in canine coronary arteries. AB - BACKGROUND: The efficacy of thrombolytic therapy in treating patients with acute myocardial infarction is limited by failure to achieve reperfusion in some patients, by the prolonged time required to achieve reperfusion, and by reocclusion of some coronary arteries. We designed this study to examine the effect of combined inhibition of thrombin and thromboxane synthesis and blockade of thromboxane A2 receptors in addition to tissue-type plasminogen activator (t PA) on thrombolysis and reocclusion in an experimental canine model with coronary thrombosis. METHODS AND RESULTS: Blood flow velocity in the left anterior descending coronary artery (LAD) of 32 anesthetized mongrel dogs was monitored by a pulsed Doppler flow probe. Coronary thrombosis was induced by applying electrical stimulation to the LAD at the site where an external constrictor was used to narrow the artery. Three hours after the formation of occlusive thrombus, animals were randomly assigned to receive one of the following: 1) t-PA (80 micrograms/kg + 8 micrograms.kg-1.min-1 i.v.) and saline; 2) t-PA and hirulog, a hirudin-based synthetic peptide and specific thrombin inhibitor (2 mg/kg + 2 mg.kg-1.hr-1 i.v.); 3) t-PA and ridogrel, a combined thromboxane A2 synthetase inhibitor and receptor antagonist (5 mg/kg + 2.5 mg.kg-1.hr-1 i.v.); or 4) t-PA, hirulog, and ridogrel. Reperfusion developed in 14% (one of seven) of dogs treated with t-PA alone at an average of 86 +/- 4 minutes after treatment, in 78% (seven of nine) of dogs treated with t-PA plus hirulog at 53 +/- 11 minutes, in 13% (one of eight) of dogs treated with t-PA plus ridogrel at 85 +/- 5 minutes, and in 88% (seven of eight) of dogs treated with t-PA, hirulog, and ridogrel at 37 +/- 10 minutes (comparison of the frequency of and the time to reperfusion, both p < 0.01). Among the dogs with reestablished coronary blood flow, reocclusion developed in the one treated with t-PA alone at 36 minutes after reperfusion, in seven of the seven treated with t-PA plus hirulog at 66 +/- 15 minutes, and in two of the seven treated with t-PA, hirulog, and ridogrel at 151 +/- 21 minutes (comparison of the frequency of and time to reocclusion, both p < 0.05). Reocclusion was not detected in the one dog treated with t-PA and ridogrel or in the other five dogs treated with t-PA, hirulog, and ridogrel within 180 minutes after reperfusion. Hirulog prolonged and maintained activated clotting times at a level twice that of baseline values. Hirulog inhibited ex vivo platelet aggregation induced by thrombin, and ridogrel inhibited platelet aggregation induced by U46619, a thromboxane mimetic. CONCLUSIONS: Inhibition of thrombin in addition to treatment with t-PA enhances thrombolysis. A combination of inhibition of thrombin and thromboxane synthetase and blockade of thromboxane A2 receptor enhances thrombolysis and delays or may prevent reocclusion of the recanalized coronary arteries. PMID- 1451272 TI - Induction of endothelial cell expression of the plasminogen activator inhibitor type 1 gene by thrombosis in vivo. AB - BACKGROUND: We have shown previously that products from activated platelets can augment synthesis of plasminogen activator inhibitor type 1 (PAI-1) in cultured endothelial and hepatoma (Hep G2) cells in vitro and increase plasma PAI-1 activity in vivo in rabbits. Accordingly, the effects of activation of platelets associated with thrombosis and thrombolysis in vivo on plasma PAI-1 activity and expression of the PAI-1 gene in endothelium, liver, and other organs were characterized. METHODS AND RESULTS: Endothelial injury giving rise to platelet rich thrombi was induced with electrical stimulation in carotid arteries in rabbits. Clot lysis and recanalization were induced subsequently with intravenous tissue-type plasminogen activator (t-PA) and verified with Doppler flow probes. Plasma PAI-1 activity (mean +/- SD) increased from 6 +/- 2 arbitrary units (AU)/ml to 129 +/- 48 AU/ml (n = 15) within several hours after recanalization. When t-PA had failed to induce recanalization, the increase was much less (from 7 +/- 2 to 42 +/- 23 AU/ml, n = 11). To define mechanisms responsible for these changes, PAI-1 messenger RNA (mRNA) was evaluated by Northern blot analysis and localized in tissues by in situ hybridization. Strong and consistent induction of PAI-1 mRNA was evident in aorta, heart, and liver of animals subjected to thrombosis (twofold to threefold increases compared with values in controls), particularly in those in which thrombolysis had been induced (fourfold to sixfold). After thrombolysis, an intense, PAI-1 mRNA-specific signal was detected in endothelium of aorta, liver, and heart, with less intense signals in endothelium of lung, adrenals, and kidneys. CONCLUSIONS: The increases in plasma PAI-1 activity follow a preceding increase in endothelial cell expression of the PAI-1 gene as reflected by PAI-1 mRNA levels. Thus, increased synthesis of endothelial cell PAI-1 after thrombosis and thrombolysis may attenuate endogenous fibrinolysis early after coronary thrombolysis, thereby potentiating early, thrombotic reocclusion. PMID- 1451273 TI - Interposed abdominal compression-CPR. Low technology for the clinical armamentarium. PMID- 1451274 TI - Transcatheter closure of patent foramen ovale. Therapeutic overkill or elegant management for selected patients at risk? PMID- 1451275 TI - Quantitative assessment of coronary artery stenosis by intravascular Doppler catheter technique. PMID- 1451276 TI - Heart rate variability in myocardial infarction. PMID- 1451277 TI - Force-frequency relation in human heart failure. PMID- 1451278 TI - Relation between ventricular depolarization duration and cardiac cycle length. PMID- 1451279 TI - CT of pelvic infection after cesarean section. AB - The CT findings in 6 women with puerperal sepsis after Cesarean section were reviewed. In four patients a right-sided mass was palpated. CT scan confirmed the diagnosis of Tubo-ovarian abscess in two of the patients, puerperal ovarian vein thrombosis (POVT) in the third and an enlarged adnexa with no signs of abscess formation in the fourth patient. The last two patients had normal adnexae but a large amount of gas in the uterus. All patients recovered after appropriate treatment. In patients with severe puerperal sepsis who do not respond to antibiotic therapy, CT scanning of the abdomen and pelvis is useful. This study can demonstrate whether there is an abscess which requires surgical intervention or POVT which needs additional anticoagulant treatment. PMID- 1451280 TI - The effectiveness of danazol therapy in postmenopausal women affected by endometrial hyperplasia. AB - Forty eight patients in postmenopause affected by histologically confirmed endometrial hyperplasia (34 with simplex and 14 with complex forms) were administered Danazol therapy, 400 mg/day for 3 consecutive months. At the end of treatment, regression of the endometrial hyperplasia was histologically ascertained in 46 patients (95.9%) with disappearance of the metrorrhagia. Endometrial atrophy was obtained in 75% of the cases, while secretive (14.7%) or proliferative (6.2%) aspects resulted in the others. Only 2 patients (4.1%) showed persistence of the hyperplastic endometrium. On the basis of this experience, treatment with Danazol appears to be effective and safe with only scarce and transient side effects. This therapy is therefore proposed as a valid alternative to progestogen therapy in cases of postmenopausal endometrial hyperplasia. PMID- 1451281 TI - Twin pregnancy in a patient with complete heart block. A case report. AB - A 22 year old primigravida with previously undiagnosed congenital complete heart block and a twin gestation is described. Early diagnosis of both problems and cardiac consultation allowed a temporary pacemaker to be inserted early in the third trimester. The patient was delivered by caesarean section at 36 weeks following spontaneous rupture of membranes. Maternal and fetal outcomes were excellent. PMID- 1451282 TI - Effectiveness of magnesium pidolate in the prophylactic treatment of primary dysmenorrhea. AB - To evaluate Magnesium (Mg) effectiveness in the treatment of primary dysmenorrhea, 30 volunteer dysmenorrheic women of mean age 22.6 years were selected from the out-patients of the Dept. of Obstetrics and Gynaecology of the University of Parma during the period January-December 1989. Patients affected by secondary dysmenorrhea were excluded from the trial. The women considered were asked to self-evaluate their menstrual pain for 6 subsequent cycles using the VAS (Visual Analogue Scale). In the first cycle, as control, no drug was administered; in the following ones, every woman was given 4.5 mg oral Mg Pidolate in 3 administrations daily, from the 7th day preceding the onset of menses till the 3rd day of menstruation. Data were statistically analyzed. In Mg treated cycles compared with the control one, first day dysmenorrhea progressively decreased, with a significant drop (p < 0.05) from the 1st to the 6th cycle. A similar trend, but not statistically significant, was seen for the 2nd and 3rd day of cycle. No side effect was remarked. These data suggest Mg administration to be a reliable therapy of primary dysmenorrhea. PMID- 1451283 TI - Vaginal sonography of the endometrium in postmenopausal women. AB - The purpose of this study was to compare transvaginal ultrasound scanning and histology of the endometrium obtained by curettage. One hundred twenty women with postmenopausal bleeding were examined by vaginal sonography, before undergoing curettage. Endometrial thickness, as measured by vaginal sonography, was used as an indicator of endometrial abnormality. The mean endometrial thickness in those women with endometrial cancer was 16.6 +/- 5.4 mm as compared with 3.2 +/- 1.1 mm in those women with atrophic endometrium, and 9.5 +/- 2.3 in those with hyperplasia. If a cutoff limit of 5 mm had been used in this study, 82% of the curettage procedures could have been avoided, without missing a single case of serious endometrial pathology. We conclude that vaginal sonography is a reliable examination in the detection of endometrial abnormality in women with postmenopausal bleeding. PMID- 1451284 TI - Fertility after ovarian cancer treatment. AB - Considering the important improvement of surgical techniques and chemotherapy in the last few years, it is possible today, in selected cases of patients previously treated for ovarian cancer, to support their desire for motherhood, thus improving the quality of life for them. The major problem for the Gynecologic Oncologist in treating young women for ovarian tumour is the lack of statistically significant experience world-wide, because of the very few cases in which the reproductive function is preserved, and pregnancy is subsequently possible. In this report the problem is discussed, and the results obtained in our Institute are presented. PMID- 1451285 TI - Bacchetti (1853) and the first electro-puncture: a milestone in the non-surgical therapy of extrauterine pregnancy. PMID- 1451286 TI - The enigma of Kaposi's sarcoma: an answer at last? PMID- 1451287 TI - Follicle mites and their role in disease. PMID- 1451288 TI - Hazards from hedgehogs: two case reports with a survey of the epidemiology of hedgehog ringworm. AB - Two related cases of ringworm caused by contact with an infected hedgehog are reported. The causal fungus, Trichophyton erinacei, was isolated from human and animal cases. The epidemiology of hedgehog ringworm is discussed. PMID- 1451289 TI - Topical fish oil in psoriasis--a controlled and blind study. AB - Omega-3 polyunsaturated fatty acids compete with arachidonic acid as substrates for lipoperoxidases, which transform them into leukotrienes with low biological activity. As this process, in skin, may benefit psoriatic patients, a randomized controlled single blind-study was carried out on a sample of 25 patients. In the study fish oil (FO) was compared with liquid paraffin (LP); both were topically applied and administered daily for 6 h under an occlusive dressing over a 4-week period. Evaluations were performed weekly assessing erythema, scaling, plaque thickness (induration) and itching. The results showed statistically significant improvement in erythema and scaling for both treatments compared to basal values; significant differences between treatments were achieved in scaling but not in erythema. Compared to baseline, FO significantly improved plaque thickness while LP did not. After 4 weeks, FO proved to be significantly better than LP. All patients accepted the treatment despite its unpleasant smell. Irritation and a burning sensation were reported in the FO treated plaque of one patient. This adverse effect reverted after completing the treatment. These findings demonstrate that topical FO shows a better performance than LP under an occlusive dressing. PMID- 1451290 TI - Topical tretinoin: a new treatment for black hairy tongue (lingua villosa nigra). AB - Black hairy tongue is the name given to the appearance of an abnormal coating of the tongue and occurs only in adults. It is the result of hyperkeratosis of the filiform lingual papillae which, on gross examination appear hair-like with a variable tinctorial aspect from yellow-brown to black. The pathogenesis is unknown and often no definite cause can be identified. A number of aetiologic factors have been implicated including the administration of topical or systemic antibiotics, poor oral hygiene, smoking, alcohol and the use of mouthwashes. Often there are no symptoms other than the aesthetic or anxiety over its aetiology. Some patients complain of gagging, nausea, alteration of taste or halitosis. The condition may be very persistent and recognized treatments include brushing with a soft tooth brush which is enhanced by the prior application of a 40% solution of urea, scraping, topical triamcinolone acetonide, gentian violet, thymol, salicylic acid, vitamin B complex, and surgical excision of the papillae. PMID- 1451291 TI - A double-blind evaluation of topical isotretinoin 0.05%, benzoyl peroxide gel 5% and placebo in patients with acne. AB - A double-blind, randomized study comparing isotretinoin gel (Isotrex), its vehicle base, and benzoyl peroxide was performed on 77 patients with mild to moderate acne vulgaris. The effect of treatment was assessed by acne grade and lesion count. The vehicle base had no effect, but both active groups produced significant improvements. Benzoyl peroxide and isotretinoin significantly reduced non-inflamed lesions at 4 (P < 0.05), 8 (P < 0.01), 12 (P < 0.01) weeks. Benzoyl peroxide had a more rapid effect on inflamed lesions, their being significant reductions at 4, 8 and 12 weeks (P < 0.01), whereas with isotretinoin there was a significant improvement at 12 weeks (P < 0.01). In addition, compared to placebo, both active treatments significantly reduced inflamed and non-inflamed lesions. Acne grade had improved significantly in the benzoyl peroxide group by 4 weeks (P < 0.01) and in the isotretinoin group by 8 weeks (P < 0.05). No significant change in haematological or biochemical parameters occurred. An irritant dermatitis occurred equally with both treatments but was well tolerated by the patients. This data confirms the clinical benefit of benzoyl peroxide in acne. The initial effect of isotretinoin on non-inflamed lesions in this study suggests that the prime mode of action is on comedone formation or separation whereas benzoyl peroxide has an effect on both comedones and inflammation. PMID- 1451292 TI - Skin conditions in epileptics. AB - The prevalence of skin and mucous membrane conditions occurring in 173 epileptics between the ages of 6 and 19 years was compared with that of an age-matched group of 211 non-epileptics. The most frequently used anticonvulants, singly or in combination, were carbamazepine in 54.9%, phenytoin in 47.8%, barbiturates in 36.6% and ethosuximide in 11.2% of epileptics. The most frequent combination was phenytoin and carbamazepine in 14% of the males and 18.4% of the females. An increased prevalence of acne was found in epileptic females; 80.3% compared to 30.2% in non-epileptic females. Hirsutism was found in 43.9% of the female epileptics compared to 7.5% of the non-epileptic females. Of interest was the finding of punctate and linear scars on the dorsum of the hands of 27.7% epileptics compared to 3.8% non-epileptics. Both ephilides and naevocellular naevi occurred in 12.7% of the epileptics compared to 29.4% and 52.1% respectively of the non-epileptics. Leukonychia was also found more frequently in epileptics than in non-epileptics; 52% and 28.9% respectively. PMID- 1451293 TI - Seborrhoea--an indicator for poor clinical response in acne patients treated with antibiotics. AB - The relationship between sebum excretion rate (SER) and clinical improvement was investigated in 255 acne patients treated for 6 months with either oral erythromycin (1 g/day), minocycline (100 mg/day), oxytetracycline (1 g/day) or cotrimoxazole (400 mg/day); topical therapy was 5% benzoyl peroxide. In all but the cotrimoxazole treated group, there was a significant correlation between a high SER and reduced clinical response. This was particularly evident in those patients with an SER of greater than 2.5 micrograms/cm2/min. These patients showed only 17% improvement compared with 100% improvement in those subjects with an SER of 1.0 micrograms/cm2/min or less. The presence of obvious seborrhoea in a patient who has failed to respond to an adequate 6-month course of antimicrobial therapy, should indicate the earlier rather than later use of isotretinoin for their acne. PMID- 1451294 TI - Coexistence of numerous superficial basal cell epithelioma of the back and non specific ulcers of the small intestine: occurrence of two rare diseases in the same patient. AB - A 53-year-old female developed multiple disseminated brownish macules that were confirmed histologically as superficial basal cell epitheliomas on her lower back. She also suffered from short bowel syndrome after repeated resection of a segment of the small intestine because of non-specific ulcers of the small intestine, a rare ulcerative disorder of unknown aetiology. The association of these two rare conditions in the same patient is of interest because it may be more than a simple coincidence. PMID- 1451295 TI - Reticulate porokeratosis--successful treatment with CO2-laser vaporization. AB - A 35-year-old male patient affected with extensive, itching skin lesions of reticulate porokeratosis is reported. He was successfully treated by CO2-laser vaporization. PMID- 1451296 TI - Unilateral linear capillaritis. AB - We present four cases of a distinctive type of pigmented purpuric eruption occurring in a striking linear and pseudo-dermatomal distribution in young males. Whilst these cases share some of the clinical and histological features of other pigmented purpuric dermatoses, they are not readily classified with any of the entities so far defined in this group of disorders. We believe these cases represent a distinct group not previously described. Four patients with an unusual pigmented purpuric eruption are presented. PMID- 1451297 TI - Inflammatory ringworm with unusual features. AB - Zoophilic dermatophyte infections are often inflammatory but severe widespread inflammatory lesions of glabrous skin, as in the female patient described, are unusual. Most cases of M. canis ringworm can be traced to an infected animal. This dermatophyte is associated with a variety of clinical presentations on glabrous skin and is being isolated with increasing frequency in some countries. PMID- 1451298 TI - Hereditary hypotrichosis (Marie-Unna type) and juvenile macular degeneration (Stargardt's maculopathy). AB - Hypotrichosis of the Marie-Unna variety is a distinctive syndrome eponymously named following a publication in 1925 describing a family in which 27 individuals in seven generations were affected by a previously unreported type of hypotrichosis. Its inheritance is determined by an autosomal dominant gene and it usually occurs as an isolated abnormality. Hereditary macular degeneration (Stargardt's maculopathy) is also well recognized and has been reported in one family in association with alopecia areata but never in association with Marie Unna hypotrichosis. Inheritance of Stargardt's maculopathy is autosomal recessive. Our patient demonstrates the co-existence of these two uncommon genetic disorders and it would appear that both defects have been independently inherited. PMID- 1451299 TI - Subcutaneous nodules as the first clinical manifestation of sarcoidosis. AB - We report the case of a 61-year-old male who presented with a febrile illness accompanied by arthralgia and myalgia. Two months later he developed multiple subcutaneous nodules and enlarged parotid glands. Later two erythematous plaques, clinically compatible with erythema nodosum (EN), were observed. Laboratory investigations revealed abnormal levels of angiotensin converting enzyme and chest radiography showed bilateral hilar enlargement. The biopsy of the cutaneous lesions demonstrated multiple non-caseating granulomas in the subcutaneous tissue without any alterations in the epidermis and the dermis. The cultures for Mycobacteria and fungi were both negative. The clinical picture and histopathological findings were compatible with subcutaneous nodular sarcoidosis. The response to steroid treatment was satisfactory. PMID- 1451300 TI - Localized multiple neurofibromas. AB - Two cases of localized multiple neurofibromas are reported. The patients had fairly large, closely grouped neurofibromas limited to a circumscribed part of the body, a very different clinical feature from segmental neurofibromatosis, but with otherwise had typical histopathological features. Possible aetiology is discussed. PMID- 1451301 TI - Wegener's granulomatosis presenting as pyoderma gangrenosum. AB - We report three cases of Wegener's granulomatosis presenting with cutaneous ulceration resembling pyoderma gangrenosum. Wegener's granulomatosis classically affects the upper and lower respiratory tracts and the kidneys. Skin involvement occurs in up to 50% of patients. Increased awareness that cutaneous involvement can take the form of pyoderma gangrenosum and that it can be a presenting sign may lead to more rapid diagnosis of Wegener's granulomatosis. PMID- 1451302 TI - Hailey-Hailey disease--exacerbation by herpes simplex virus and patch tests. AB - Benign familial chronic pemphigus, or Hailey-Hailey disease, is a rare hereditary condition characterized by development of blisters at sites of friction such as the neck, axillae and groin. Contact sensitivity to topical medications is reported to be common and routine patch testing has been strongly advocated. We report a case of Hailey-Hailey disease in a 43-year-old veterinary surgeon who presented with an acute exacerbation of his disease caused by herpes simplex virus type 1 (HSV). Patch testing was carried out to exclude a coexistent contact dermatitis and was complicated by severe local blistering. We are reporting this case to remind clinicians that HSV is a recognized cause of exacerbations of this disease and to warn that patch testing is not without hazard. PMID- 1451303 TI - Acute monocytic leukaemia in a HIV-seropositive man. AB - Individuals infected with the human immunodeficiency virus (HIV) have been reported to develop a number of malignant neoplasms. We recently treated an HIV patient who had acute monocytic leukaemia which was first evident in the skin. To our knowledge, this is the first report of a case of acute monocytic leukaemia occurring in a HIV-infected person. PMID- 1451304 TI - Acquired eruptive haemangiomata with primary biliary cirrhosis and prostatic carcinoma. AB - We report a male patient with acquired eruptive haemangiomata occurring in association with primary biliary cirrhosis and a carcinoma of the prostate. The possible explanations include an abnormality of sex sterol metabolism associated with his liver disease, secretion of an angiogenic factor by his carcinoma or a combination of the two mechanisms. PMID- 1451305 TI - Atypical systemic sclerosis following exposure to vinyl chloride monomer. A case report and review of the cutaneous aspects of vinyl chloride disease. AB - An unusual case of systemic sclerosis occurring in a patient exposed to the vinyl chloride monomer (VCM) is presented. The dermatological aspects of vinyl chloride disease (VCD) are outlined and the mechanisms of pathogenesis discussed. PMID- 1451306 TI - Normolipaemic plane xanthomas: an association with increased vascular permeability and serum lipoprotein(a) concentration. AB - We present a normolipaemic young man with extensive facial plane xanthomas and xanthelasmas with a high level of lipoprotein(a) and possibly increased vascular permeability. These associations are of potential importance in understanding the pathogenesis of xanthoma formation and in the identification of patients at risk from coronary atherosclerosis. PMID- 1451308 TI - Minimizing the pain of local anaesthesia. PMID- 1451307 TI - Selenium plasma levels in psoriasis. AB - Little is known about factors that may have modulating effects on inflammatory diseases such as psoriasis. Recently it has been proposed that trace elements like selenium may play an active role. Selenium concentrations were determined in plasma and in whole blood from 64 patients with psoriasis. Values were compared with those of matched controls: no significant reduction was observed in contrast with previous reports of reduced selenium levels in psoriasis. PMID- 1451309 TI - Pemphigus associated with multiple sclerosis. PMID- 1451310 TI - Mucocutaneous infections with herpes simplex virus and their management. PMID- 1451311 TI - Factitious purpura. AB - Factitious purpura may present as a perplexing problem for the dermatologist and can mimic serious disease. This form of mechanical purpura, often caused by suction may be deliberately or unknowingly induced by the patient. Some cases may go unrecognized for a considerable length of time and undergo unnecessary investigation before the diagnosis is realized. Three cases of purpura are reported in which the causative agents were very different. PMID- 1451312 TI - Flow cytometry analysis of adhesion molecules on human Langerhans cells. AB - The Langerhans cell (LC) migrates between the epidermis and the regional lymph nodes to present antigens. This migration pattern requires the expression of a changing repertoire of cell-surface molecules. In this work, we have investigated the expression of the adhesion molecules CD 11/CD 18 and CD 58 on LCs. Human epidermal cell suspensions were enriched in LCs (mean enrichment 75%) using a two step technique including a Ficoll-Hypaque gradient followed by Fc receptor panning with IgG-coated sheep erythrocytes. The number of cells obtained per experiment was 750,000 (extremes 280,000-1,800,000), and the following antibodies were tested on fresh suspensions and/or after 48 hours in culture: BB3 (antithyroglobulin negative control IgG2a), OKT6 (anti CD1a, Ortho), anti HLA-DR (Becton-Dickinson), MHM 24 (anti CD 11a, leukocyte typing workshop n(0)3), MO1 and 44 (anti CD 11b, leukocyte typing workshop n(0)3), anti CD 11c (Immunotech), 60.3 and MHM 23 (anti CD 18, leukocyte typing workshop n(0)2), TS2/9.1.1 (anti CD 58, leukocyte typing workshop n(0)3). We found that amongst CD 11 subunits, only CD 11c was expressed in fresh suspensions, but was weaker than CD 18, and disappeared with culture. CD 58 was not detected in fresh suspensions but appeared after 2 days of culture, confirming earlier work. Thus the LC exhibits cell surface characteristics similar to tissue macrophages (CD 18 and CD 11c) prior to culture. The expression of CD 58 after culture is in accordance with the interaction of LC with CD2 bearing T-lymphocytes during antigen presentation in peripheral lymph-nodes. PMID- 1451313 TI - An evaluation of the irritancy potential of povidone iodine solutions: comparison of subjective and objective assessment techniques. AB - A double-blind study has been carried out in 12 normal volunteer subjects in order to determine the relative irritancy of povidone-iodine solutions. Aqueous solutions of 10% povidone-iodine (PI), standardized 10% povidone-iodine (SPI) and reformulated standardized 10% povidone-iodine (RSPI) were applied to the backs and occluded using aluminium chambers. At 1, 2, 3, 4, 5, 6, and 8 hours, chambers were removed and the degree of cutaneous irritancy assessed. As well as subjective assessment of erythema, objective measurement of skin colour was performed using an erythema meter. In addition, laser Doppler blood-flow measurements have been carried out. The results show a rapid increase in cutaneous irritancy as evidenced by an increase in visual scores of erythema, increased erythema meter readings and increased cutaneous blood-flow. The increase was greatest for SPI treated sites for all three methods. Statistically these differences were significant at P < 0.05. Thus in this controlled study it has been possible to discriminate between the similar formulations in terms of their cutaneous irritancy. PMID- 1451314 TI - Acute Achilles tendonitis following oral isotretinoin therapy for acne vulgaris. AB - We report three cases of acute Achilles tendonitis following administration of isotretinoin for acne vulgaris. In this rarely documented side-effect, the symptoms were intimately related to the isotretinoin therapy. Modification of dose regimes permitted control of the tendonitis and an eventual successful response to isotretinoin therapy. Oral isotretinoin has been in use for more than 10 years and is known to cause a wide variety of predictable side-effects the most common of which are cutaneous and dose related. Musculoskeletal problems are also well known to occur and these include myalgia, arthralgia and less commonly arthritis and muscle damage, however, isolated Achilles tendonitis has been reported on a rare and sporadic basis. We wish to report a series of three patients who developed acute Achilles tendonitis during administration of isotretinoin for acne. PMID- 1451315 TI - The efficacy of methotrexate in psoriasis--a review of 40 cases. AB - Forty patients with psoriasis treated with methotrexate (MTX) are reviewed. MTX was particularly effective in controlling erythrodermic and generalized pustular psoriasis. The treatment was discontinued in seven patients due to nausea in two and because of abnormal laboratory tests in five. Two patients developed toxic epidermal necrolysis (TEN) and died. Patients under 60 years of age had a liver biopsy before treatment and repeat biopsy after each cumulative MTX dose of 1500 mg. We consider that MTX is the drug of choice for treating difficult psoriasis. PMID- 1451316 TI - Myiasis due to Parasarcophaga argyrostoma--first recorded case in Britain. AB - A case is described of a 79-year-old man in whom a gangrenous toe was invaded by maggots of the flesh fly Parasarcophaga argyrostoma. This is the first recorded case of myiasis by this fly in Britain. PMID- 1451317 TI - Toxic epidermal necrolysis treated with cyclosporin. AB - Toxic epidermal necrolysis (TEN) is a severe life-threatening disorder which has many features in common with graft-versus-host disease. However, immunosuppression with steroids gives disappointing results and is possibly detrimental. We treated two patients who had TEN with a combination of cyclosporin and steroids which resulted in an apparent halt to the evolution of the disease, and a further relapse was aborted using cyclosporin in one of these patients. We feel that the use of this drug in the early treatment of TEN where it is used as a specific therapy aimed at the primary immunopathological events and is used in conjunction with the supportive care patients require, needs to be further evaluated. PMID- 1451318 TI - Skin nodules and macules resembling vasculitis in the antiphospholipid syndrome- a report of two cases. AB - Two patients who demonstrated skin lesions in the presence of antiphospholipid antibodies are documented. The first had a long history of recurrent painful nodules. She had also suffered two deep vein thromboses. The second developed a rash on the lower limbs resembling vasculitis which did not respond to prednisolone, but to low dose salicylate therapy. Histology in both patients revealed microthrombosis of cutaneous vessels. PMID- 1451319 TI - A primary cutaneous multi-lobed B-cell lymphoma. AB - Multi-lobed non-Hodgkin's lymphoma (NHL) has recently been recognized as a NHL variant. A patient presented with a scalp nodule which, upon skull X-Ray, was seen to be associated with a bone defect. Immunophenotyping clearly demonstrated that this was a B-cell proliferation. Histologically the B-lymphocytes were closely related to centroblasts. There were no other extra cutaneous localizations. The present report emphasizes the importance of this clinico anatomical entity which shows prominent extra-nodal involvement, large lymphoid cells with multi-lobed nuclei and a good response to chemotherapy. Multi-lobed NHL may be a T-cell lymphoma, or a B-cell lymphoma closely related to centroblastic NHL. Although multi-lobed lymphomas have a predilection for cutaneous localizations, our case is the first primary cutaneous multi-lobed B NHL, proven by immunophenotyping. PMID- 1451320 TI - Leukonychia due to cytostatic agents. AB - Chromonychia induced by antineoplastic agents has been known for several years. The most frequent of these is melanonychia, either diffuse or in tranverse or longitudinal bands, that may co-exist with diffuse pigmentation of the skin. Although any cytostatic agent may be involved in melanonychia, this condition appears most commonly after treatment with adriamycin and cyclophosphamide or in polychemotherapy. Leukonychia, either true or apparent, seems to be less frequent and is the reason for our reporting two patients with this colour change. PMID- 1451321 TI - Langerhans-cell histiocytosis in an adult patient with multiple myeloma. AB - A 44-year-old man who had suffered for 6 years from multiple myeloma developed multiple papules on the face and chest. Histological examination of these papules revealed the infiltration of predominantly histiocytic cells into the dermis and into parts of the epidermis. These cells were seen on electron-microscopic study to have Langerhans granules in the cytoplasm, which led to a diagnosis of Langerhans-cell histiocytosis concomitant with multiple myeloma. Possible explanations for this unusual association are discussed. PMID- 1451322 TI - ILVEN responding to occlusive potent topical steroid therapy. PMID- 1451324 TI - Abstracts from the 19th annual meeting of the Society for Cutaneous Ultrastructural Research. Lyon, France, 17-19 September 1992. PMID- 1451323 TI - Skin metastasis in laryngeal carcinoma. AB - Cutaneous metastases from carcinoma of the larynx are very rare. We observed a 64 year-old Japanese patient with squamous cell carcinoma of the larynx who developed a subcutaneous nodule on the abdomen. It was found to be a metastatic tumour from the laryngeal cancer, histopathologically as well as histochemically. PMID- 1451325 TI - Is thymosin alpha 1 a thymic hormone? PMID- 1451326 TI - Elevation of feline interleukin 6-like activity in feline immunodeficiency virus infection. AB - The involvement of feline interleukin 6 (IL-6)-like activity in polyclonal B-cell activation in feline immunodeficiency virus (FIV) infection was investigated by using the proliferative response of hybridoma cell clone B3B1. Cats spontaneously infected with FIV had hyperimmunoglobulinemia, as shown by increases in the percentage of gamma-globulin and the plasma IgG concentration and decrease in the albumin/globulin (A/G) ratio. Because IL-6 plays an essential role in the differentiation of activated B cells into Ig-secreting cells, we examined the effect of FIV infection on the plasma IL-6 level. Plasma IL-6-like activity was found to be significantly higher in FIV-infected cats than in healthy controls. Peripheral blood mononuclear cells (PBMC) isolated from FIV-infected cats and cultured without any exogenous activators of IL-6 production released more feline IL-6-like activity than cells from healthy controls. This phenomenon was mainly due to the increase in the production of IL-6 by adherent cells such as monocytes/macrophages, but also partly by nonadherent cells. These results indicate that elevation of feline IL-6-like activity is associated with FIV infection and that overproduction of IL-6 may contribute to the polyclonal B-cell activation seen in FIV infection. PMID- 1451327 TI - Expanded macrophage precursor populations in BXSB mice: possible reason for the increasing monocytosis in male mice. AB - The BXSB mouse spontaneously develops an autoimmune disease that resembles human systemic lupus erythematosus (SLE). During their lifetime, male BXSB mice show an increasing monocytosis in the peripheral blood as opposed to their female littermates. This monocytosis is unique among autoimmune-prone mice. To test the hypothesis that alterations at the stem cell level may be responsible for this monocytosis, myeloid bone marrow precursor cells were examined in both male and female BXSB mice from 4 to 40 weeks of age. The number of M-CSF responding stem cells (CFU-M) and the number of GM-CSF responding stem cells (CFU-GM) were higher than in all other inbred mouse strains tested. In addition, male BXSB mice developed a progressive increase of CFU-M and CFU-GM in the bone marrow during their lifetime, which paralleled the peripheral blood monocytosis. The monocytosis in male BXSB mice is the result of a further expansion of the strain specific high number of macrophage precursors by intrinsic factors, which may be attributed to the influence of the Yaa factor. The sex-specific expanded mononuclear phagocyte system may promote the autoimmune process and may be one reason for the dramatic course of murine SLE in male BXSB mice. PMID- 1451328 TI - Attenuation of murine acute lethal graft-versus-host disease by the administration of DL-alpha-difluoromethylornithine. AB - Intravenous injection of 5 x 10(7) C57BL/6 (B6) lymphocytes into adult (C57BL/6 x DBA/2)F1 recipient mice results in acute lethal graft-versus-host (ALGVH) disease. This disorder is characterized by anemia, a diminished number of splenocytes, impaired cytotoxicity (CTX) against third party alloantigen, and impaired natural killer cell (NK) activity. Parental anti-F1 CTX is critical to the induction of ALGVH disease, and CTX in general has been reported to be dependent upon the presence of the low molecular weight polyamines essential for cell growth and differentiation. We now report that DL-alpha difluoromethylornithine, a specific inhibitor of polyamine biosynthesis, attenuates the clinical expression of disease in mice undergoing ALGVH disease. PMID- 1451329 TI - Immune response to tumor antigens in a patient with colorectal cancer after immunization with anti-idiotype antibody. AB - An active vaccination protocol was performed on one patient with colon carcinoma as a pilot to a prospective randomized double-blind clinical trial with the vaccine SDZ SCV 106. This vaccine is an anti-idiotype goat antibody to the monoclonal antibody 17-1A, which is directed against the tumor antigen 17-1A. To study the effect of the therapy on the immune reactivity, several tests were performed to detect anti-tumor antibodies in the serum as well as in eluates of metastatic tissue. Furthermore metastases removed from the lung were examined by immunohistochemistry. The results suggest that the humoral and cellular immune reactivity against the tumor are enhanced. PMID- 1451330 TI - Cytokine production and serum levels in systemic sclerosis. AB - Serum levels of various cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL1-beta), and interleukin 2 (IL2), and of soluble IL2 receptors (sIL2R) were determined in 30 patients with definite systemic sclerosis (SSc). Spontaneous and lipopolysaccharide-or mitogen-induced production of the cytokines, TNF-alpha, IL1-beta, and IFN-gamma, by peripheral blood mononuclear cells (PBMNC) of these SSc patients was measured by immunoassays. The patients were divided into three groups: 12 with limited cutaneous disease (lcSSc), 7 with diffuse cutaneous disease (dcSSc) < 3 years duration, and 11 with dcSSc > 3 years duration. None were treated with cytotoxic drugs or biologic response modifiers. Sera of patients with SSc had elevated sIL2R levels, and only low levels of IL2 (1-2 U/ml) were detected in 10/29 sera tested. Spontaneous production of TNF alpha and IL1-beta by PBMNC of patients with SSc (829 pg/ml +/- 215 SEM and 728 pg/ml +/- 186, respectively) was significantly higher than that by normal PBMNC obtained from 30 volunteers (25 +/- 10 and 34 +/- 6 pg/ml, respectively) and tested at the same time as patients' PBMNC. The largest increases in spontaneous release of TNF-alpha or IL1-beta were seen in patients with early dcSSc. No significant difference in spontaneous IFN-gamma production by patient or control PBMNC was detected. On the other hand, the mean level of mitogen-induced IFN gamma production by PBMNC was significantly depressed in patients with SSc (103 U/ml +/- 18 vs 255 +/- 33 U/ml in controls). In vitro-induced production of TNF alpha or IL1-beta by patients' PBMNC was comparable to that of normal PBMNC. These data indicate that in vivo-activated PBMNC of patients with SSc spontaneously secrete excessive amounts of fibrogenic cytokines, which are involved in modulation of connective tissue synthesis. PMID- 1451331 TI - Parathyroid hormone inhibits immunoglobulin production without affecting cell growth in human B cells. AB - The effect of parathyroid hormone (PTH) on immunoglobulin (Ig) production and proliferation in the human B-cell lines CBL, SKW, and CESS was studied. PTH inhibited Ig production from all the B-cell lines in a dose-dependent manner during 5 days of culture. As little as 0.1 ng/ml was inhibitory. PTH also inhibited Ig production from cell lines stimulated by vasoactive intestinal peptide (VIP), interleukin 2 (IL-2), and IL-6. This inhibition was not due to decreased cell growth since proliferation was not affected and cell viability was always greater than 98%. In contrast to PTH, inactivated PTH or triiodothyronine failed to affect Ig production. Inhibition by PTH was blocked by anti-PTH serum, but not by control serum. Of the various cytokines tested, IL-4 reduced the PTH induced inhibition of Ig production, whereas other cytokines, including IL-1 beta, IL-3, IL-5, interferon alpha (IFN-alpha), IFN-gamma, and granulocyte macrophage colony-stimulating factor (GM-CSF), failed to do so. The reducing effect of IL-4 was blocked by anti-IL-4 antibody but not by control antibody. Moreover, IFN-alpha and IFN-gamma, but not GM-CSF, overcame the reducing effect of IL-4. PTH also inhibited IgG, IgM, and IgA production by tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I (SAC) and IL-6 without affecting proliferation. This inhibition was blocked by anti-IL-4 antibody but not by control antibody. These results indicate that, in addition to its regulatory effect on calcium metabolism, PTH also acts as an immunoregulatory factor, and that it interacts with the cytokine, IL-4. PMID- 1451332 TI - Association between mast cells and the development of experimental autoimmune uveitis in different rat strains. AB - To study the role of anterior uveal mast cells in experimental autoimmune uveitis (EAU), the mast cells in the iris and ciliary body of Lewis rats, Brown Norway (BN) rats, and their F1 hybrids (LBNF1) were quantitated in normal rats and during the induction period of EAU. The mean baseline mast cell number was 68.9 +/- 10.8 per anterior uvea for Lewis rats, 0.3 +/- 0.2 for BN rats, and 4.6 +/- 0.6 for LBNF1 rats. Detectable mast cells in the anterior uvea of S-Ag-immunized Lewis rats decreased to 60% of control at 6 days postimmunization, recovered to 80% at 10 days, and dropped again to 16% at 13 days, with disease onset around 14 days. In Lewis rats that were adoptively transferred with a uveitogenic T lymphocyte line, a profound drop in anterior uveal mast cell numbers occurred in the eyes with early signs of EAU, 3 days after the transfer. The decrease in detectable mast cells is consistent with mast cell degranulation. The data suggest that anterior mast cells participate in the immunopathogenesis of EAU and may influence the genetic susceptibility to EAU. PMID- 1451333 TI - Effect of exogenous cytokines on the inhibition of macrophage-induced, antigen specific T cell proliferation by poly(I:C). AB - We have previously demonstrated that IFN-alpha/beta, poly(I:C) (an inducer of IFN alpha/beta), or IFN-gamma can inhibit the ability of KLH-pulsed peritoneal macrophages (M phi) to induce the proliferation of syngeneic, KLH-immune T lymphocytes from CBA/J mice. In this study we investigated whether the mechanism by which poly(I:C) inhibits M phi-induced, antigen-specific T cell proliferation involved decreased cytokine production by poly(I:C) treated KLH-pulsed M phi or by T cells cultured with these M phi. The production of IL-2 by T cells cultured with poly(I:C)-treated, KLH-pulsed M phi was decreased by 80%; however, addition of exogenous rIL-2 could not restore proliferation. Although IL-1 production by poly(I:C)-treated M phi was comparable to the level produced by saline-treated, KLH-pulsed M phi controls, addition of exogenous rIL-1 was still examined to explore the possibility that a greater amount of IL-1 may be needed to induce T cell proliferation with poly(I:C)-treated, KLH-pulsed M phi. Increasing concentrations of rIL-1 alone or with rIL-6 did not abrogate the inhibition of M phi-induced, antigen-specific T cell proliferation by poly(I:C). Interestingly, the addition of combinations of IL-1 and IL-6 increased the proliferation of T cells in response to KLH presented by either saline- or poly(I:C)-treated M phi. The effect of the combination of rIL-1 and rIL-6 was synergistic in that addition of either monokine alone had no effect on T cell proliferation. These results suggest that although poly(I:C)-induced inhibition of T cell proliferation is not due to insufficient quantities of IL-1, IL-2, or IL-6, a combination of IL-1 and IL-6 can augment proliferation of freshly isolated T cells in response to antigen presented by freshly isolated accessory cells. PMID- 1451335 TI - ETB interactive technology resources for nurse educators. PMID- 1451334 TI - Heterozygosity of the major histocompatibility complex controls the autoimmune disease in (NZW x BXSB) F1 mice. AB - In the F1 hybrid of phenotypically normal NZW (H-2z) and systemic lupus erythematosus (SLE)-prone BXSB mice (H-2b), features of the disease became more severe than those seen in the BXSB mice, regardless of the presence or absence of the Yaa (Y-chromosome-linked autoimmune acceleration) mutant gene. To determine whether the gene(s) linked to the major histocompatibility complex (MHC) of NZW mice is involved in this event, we developed the H-2-congenic NZW.H-2d strain and compared the severity of autoimmune disease between (NZW x BXSB) F1 (H-2z/b) and (NZW.H-2d x BXSB) F1 mice (H-2d/b). The H-2z/b, but not H-2d/b, heterozygous F1 mice of both sexes showed an accelerated, higher incidence of proteinuria and a more severe thrombocytopenia than did the BXSB mice. In NZW x (NZW x BXSB) F1 backcross mice, the H-2z/b heterozygous progeny showed more severe disease than did the H-2z/z homozygotes. Thus, disease-accelerating events in (NZW x BXSB) F1 mice are linked to the H-2z/b heterozygosity. Because H-2d/z heterozygosity plays a crucial role for SLE in (NZB x NZW) F1 mice, in which SLE features differ from those in (NZW x BXSB) F1 mice, the present observations may imply that the different but related MHC heterozygosity acts as a predisposing genetic element in these different SLE syndromes. PMID- 1451336 TI - Classification of diabetes in patients with end-stage renal disease. Validation of clinical criteria according to fasting plasma C-peptide. AB - An epidemiologic study of end-stage diabetic nephropathy in France (Uremidiab) was performed, aiming to establish the prevalence of both types of diabetes in dialysis patients. Because discrimination between type I and type II diabetes remains mostly clinical, our aim was to evaluate what the most fitted clinical criteria were. We studied 494 hemodialyzed diabetic patients. A first classification (Cn) was offered by the nephrologist. Clinical data of 472 patients (22 patients of the 494 have been excluded) were then collected with a standardized questionnaire, allowing one diabetologist of us to establish the diagnosis of type of diabetes (classification Cd). Plasma C-peptide at this stage of the disease was expected to be very discriminative, measured in 88 patients and defined classification Ccp (< or = 0.6 ng/ml = "negative C-peptide" = type I, > 0.6 ng/ml = "positive C-peptide" = type II). Classification Cd observed 98 type I and 374 type II diabetes. Cn overestimated type I diabetes, 37% of type II diabetes being misclassified because insulin-treated. Classification Ccp observed 74 positive C-peptide patients, classified as type II, among whom 45 were insulin treated. Only 3 patients were discordant for classification Cd and Ccp. Predictive value of "negative C-peptide" and "positive C-peptide" were 100% and 96% respectively. Multiple regression analysis of the Ccp classification was performed with the clinical criteria and showed very significant correlation with: age at the time of diagnosis of diabetes (AGE), maximal body mass index ever reached (BMI MAX) and delay between diagnosis and consistent insulin use (DI).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451337 TI - Proteinuria and renal function in relation to renal morphology. A clinicopathological study of IgA nephropathy at the time of kidney biopsy. AB - At the time of kidney biopsy the pattern of urinary protein excretion (UPE) and renal function were studied in 54 patients (age 16-62 years) with IgA nephropathy (IgAN). Serum and urinary albumin (alb), IgG, beta-2-microglobulin and creatinine were analysed, and excretion rates (UV) and clearances were calculated. The glomerular filtration rate (GFR) was determined by plasma 51Cr-EDTA clearance (51Cr-EDTA) and by 24-hour creatinine clearance (C-Cr 24 h). Glomerular mesangial (volume expansion and cell proliferation), tubulo-interstitial (fibrosis and inflammation) and vascular lesions were classified semiquantitatively on a five degree scale, and the percentage of glomeruli showing global sclerosis, segmental sclerosis and cellular crescents was calculated. One third of our patients had reduced renal function, three patients uremia and 70 per cent of the patients overt albuminuria. The mean GFR was reduced in microalbuminurics and further decreased in albuminurics and nephrotics. A lower GFR and more proteinuria were found in the patients with more advanced morphological lesions also when the uremic patients were excluded. Segmental glomerular sclerosis correlated with GFR as well as with UalbV and UIgGV, while global sclerosis correlated only with GFR. UalbV and UIgGV also correlated with the extent of interstitial damage but not with mesangial lesions. In summary an accurate determination of GFR and UPE at the time of the kidney biopsy may give an indication of the extent of renal damage. A lowered GFR was also found in mild proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451338 TI - Growth, serum lipoproteins and apoproteins in infants with congenital nephrosis. AB - Retarded growth and extremely high cholesterol levels have been reported in infants with congenital nephrotic syndrome of the Finnish type (CNF). In an attempt to normalize growth and lipid disturbances the high-calorie diet (130 kcal/kg/d) containing protein 4 g/kg/d and supplemented with unsaturated fatty acids (mean P/S-ratio 1.40) was given to ten infants with CNF from birth. Growth, lipoprotein and apoprotein concentrations were measured. All patients exhibited normal growth, which allows renal transplantation, the only life-saving treatment in CNF, already at an early age. In spite of the diet lipid profiles at 3 and 9 months revealed marked elevation of triglyceride in all lipoproteins, especially in VLDL fraction, compared to controls. The abnormalities increased significantly with time (p for VLDL-TG 0.04). The elevation of serum cholesterol was mainly attributable to the increase of cholesterol in triglyceride-rich particles (chylomicrons, VLDL, IDL). Analysis of VLDL, LDL and HDL revealed significant triglyceride enrichment and cholesterol deficiency in all lipoproteins. The concentrations of the low-molecular weight apoproteins A-I and A-II were significantly decreased, but the concentration of high-molecular apo B was high. Urinary analysis revealed progression and decreasing selectivity of proteinuria with time. Thus the mechanisms leading to lipid abnormalities in CNF are multiple including stimulated hepatic lipoprotein synthesis, impaired conversion of VLDL and IDL to LDL, compositional changes, urinary loss of low-molecular apoproteins and presumably reduced LPL activity. The abnormalities indicate an increased risk of arteriosclerosis in CNF patients. PMID- 1451339 TI - Lipids and apolipoproteins change during the progression of chronic renal failure. AB - Uremic hyperlipidemia was recently suggested to contribute to progression of chronic renal failure (CRF). To investigate the relationship between lipoprotein abnormalities and decline of renal function, plasma lipids with apoproteins A1, B, E, CII, CIII, CII/CIII and E/CIII ratios, parathyroid hormone (PTH), insulin and glucose levels were examined in 72 patients with different degrees of CRF and compared to 28 patients of a reference group. A significant decrease of CII/CIII ratio was already evident below a Ccr of 60 ml/min, while increased apo-CIII and triglycerides (TG) with reduced HDL-cholesterol (HDL-C) levels occurred below a Ccr of 30 ml/min. Both TG and apo-CIII showed a positive correlation with creatinine levels. On the contrary, apo-CII/apo-CIII and HDL-C inversely correlated with the progression of renal failure. PTH and insulin showed a positive correlation with TG, the former being also inversely related to apo CII/apo-CIII ratio. Our results point to early apolipoprotein changes in the course of CRF. Elevated apo-CIII and reduced apo-CII/apo-CIII ratio may be considered the most typical features of uremic hyperlipidemia and likely account for the impaired TG removal and the hypertriglyceridemia (HTG). Secondary hyperparathyroidism may contribute to reduce peripheral lipolytic activity and cause HTG. A contributory role of hyperlipidemia in the progression of renal disease is also supported. PMID- 1451340 TI - High serum lipoprotein(a) concentrations in uremic patients treated with continuous ambulatory peritoneal dialysis. AB - We measured serum lipoprotein(a) [Lp (a)] concentrations in 50 uremic patients treated on continuous ambulatory peritoneal dialysis (CAPD) and compared them with those in 29 uremic patients on hemodialysis (HD) and those in 62 normal controls. The median values were 47.9 mg/dl in CAPD patients, 25.2 mg/dl in HD patients, and 11.7 mg/dl in controls, respectively. These differences were statistically significant when assessed by Kruskal-Wallis test (p < 0.0001). Thirty-five out of 50 patients on CAPD (70%) and 12 out of 29 patients on HD (41%) had Lp(a) concentrations above 30 mg/dl, whereas these high values were observed in only 15% of normal controls. This difference in prevalence of high Lp(a) was also significant by 2 x 3 chi-square test (p < 0.01). There was a significant positive correlation between Lp(a) and apolipoprotein B (r = 0.517, p < 0.0001). In CAPD patients, 9 with ischemic heart disease had a significantly higher median Lp(a) than those without it (67.4 vs 40.9 mg/dl, p < 0.01 by Mann Whitney U-test). These results suggest that high levels of serum Lp(a) might contribute to an increased risk for ischemic heart disease in CAPD patients, and that there may be a relationship between Lp(a) and apolipoprotein B metabolism in CAPD patients. PMID- 1451341 TI - The effects of recombinant human erythropoietin on hemostasis and fibrinolysis in hemodialysis patients. AB - Thromboembolism might complicate the treatment of patients with chronic renal failure with Recombinant Human Erythropoietin (ReHuEPO). In order to detect prothrombotic changes, a number of hemostatic and fibrinolytic parameters was determined during ReHuEPO treatment of fifteen chronic hemodialysis patients (mean age 47.1 years; ten females, five males). To avoid the influence of hemoconcentration and/or dilution, the patients were kept normovolemic, using the method of echography of the inferior vena cava diameter. In a first group of eight patients, we investigated platelet count and function. During ReHuEPO, a significant rise of hematocrit (19 +/- 3 to 34 +/- 5%, p < 0.001) was observed. Bleeding time shortened (7'33'' +/- 3'39'' to 3'41'' +/- 3'19''; p < 0.001) and platelet count increased (222 +/- 45 to 254 +/- 49 10 9/l; p < 0.005). The initial negative in vitro spontaneous platelet reactivity became positive in two of them, whereas the decrease in ADP threshold in the whole group (2.0 +/- 0.1 to 1.10 +/- 0.4 mumol, p < 0.02) indicated an increased induced platelet reactivity. In all patients prothrombotic changes were observed. The protein-C antigen and protein-C activity and the total and free protein-S antigen decreased significantly. The plasminogen activator inhibitor (PAI) activity in the whole group did not change significantly (6.4 +/- 4.1 to 5.4 +/- 4.8 AU/ml). However, in the patients with fistula thrombosis (n = 3), higher values in all test points were found compared to those without thrombosis. PMID- 1451342 TI - RBC improved survival due to recombinant human erythropoietin explains effectiveness of less frequent, low dose subcutaneous therapy. AB - Effectiveness of less frequent, once weekly, low dose subcutaneous recombinant human erythropoietin (rHuEPO) in maintaining 35% hematocrit in patients with chronic renal failure, predialysis and ESRD receiving dialysis, is dependent on rHuEPO induced prolonged RBC survival. One year of weekly rHuEPO doses to 7 patients originally part of the National Cooperative Protocol were evaluated for a total of 372 weeks for an average of 53 weeks per patient. The original 8 to 12 week dosage was directed by protocol for units per dose at 3 doses per week (4 IV, 3 subcutaneous). Thereafter, all doses were subcutaneous. Units/dose and doses/week were titrated to keep hematocrit at 35-38%. Dosage reduction of rHuEPO was determined by two investigators at the time of each examination. Statistical correlation was performed on effect of rHuEPO on 51Cr T1/2 RBC survival changes and changes of rHuEPO weekly doses. Patients evaluated at specific time points in the study were compared to themselves as their own controls by paired t-test analysis. The long-term increased RBC count correlated with prolonged RBC survival by 51Cr T1/2 rather than reticulocytosis. A relatively increased ease of sustaining the target hematocrit of 35% was demonstrated from the 8th week to 1 year. Thirty-two percent of the expanded RBC mass was older at 12 weeks and 22% was older at 1 year. rHuEPO dosage was reduced to 27% at weeks 8-12, to 21% at weeks 20-24, and to 38% at 1 year corresponding to prolonged RBC survival. 51Cr T1/2 increased from 21.6 days control to 28.6 days at 12 weeks and 26.3 days at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451343 TI - Is folate supplementation necessary in hemodialysis patients on erythropoietin therapy. AB - The need for folate supplementation in hemodialysis (HD) patients receiving erythropoietin (EPO) therapy remains unknown. Twenty stable HD patients, taking folic acid, 5 mg, after a meal during each HD session were divided into two groups. Supplementation was withdrawn at the start of the study in group 1 and after a 12-month-observation period in group 2. EPO treatment, 1500 u x 3/week i.v. was started in both groups. Pre- and post-HD blood samples were obtained at the beginning of the study for baseline values, then 12 and 18 months later. Folate levels decreased to normal after withdrawal of the supplements. The response to EPO treatment was exactly the same in both groups and the anemia was effectively improved. We conclude that there is no need for routine folic acid supplements in HD patients receiving EPO therapy if they are eating an adequate mixed diet. PMID- 1451344 TI - Crescentic glomerulonephritis in a patient taking penicillamine associated with antineutrophil cytoplasmic antibody. PMID- 1451345 TI - Fungus ball: a cause of early obstructive uropathy in renal transplantation. PMID- 1451346 TI - Up-regulation of TIMP-1 expression in B16-F10 melanoma cells suppresses their metastatic ability in chick embryo. AB - Clonal B16-F10 cell lines with increased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) have been generated by transfection with a TIMP-1 containing expression vector. The parental B16-F10 and control 1-2 cells, and two TIMP-1 up-regulated clones (2-10, 6-5), were studied for their growth characteristics in tissue culture and their experimental metastatic ability in the chick embryo. Both of the TIMP-1 up-regulated clones showed slower in vitro growth and had lower saturation densities. Both clones were also less metastatic following intravenous injection into chick embryos, and formed significantly fewer metastatic tumors in the chorioallantoic membrane and in the liver than did parental B16-F10 and control cells. Furthermore, the size of tumors formed by TIMP-1 up-regulated cells was significantly reduced in comparison to the tumors produced by B16-F10 or control cells. Our results show that malignant cell lines genetically modified to express increased levels of TIMP-1 exhibit a suppressed experimental metastatic ability in vivo. We propose that TIMP-1 suppresses metastatic ability by decreasing both invasive and growth abilities. PMID- 1451347 TI - Suppression by interferon-gamma of tumor cell-induced increase in mesothelial permeability. AB - The effect of interferon-gamma (IFN-gamma) on the interaction between tumor cells and mesothelial cell layers was studied from the aspect of changes in mesothelial permeability. Mesothelial permeability was assessed as the percentage diffusion of radiolabeled albumin across the mesothelial cell sheets on Matrigel-coated filter cup assemblies. When lined gastric carcinoma cells (KATO-III) were seeded on the confluent mesothelial cell layers, the fine cobblestone appearance of the cell sheet was disrupted and mesothelial permeability significantly increased. The increase in permeability was suppressed by the addition of as little as 1 U/ml of IFN-gamma. The effect of IFN-gamma was observed when either the conditioned medium of tumor cells alone or the IFN-gamma-resistant tumor cells, K 562, was placed onto the mesothelium. The cobblestone appearance of the cell sheet was relatively well preserved in the presence of IFN-gamma. In contrast, IFN-alpha did not suppress tumor-induced mesothelial permeability. These results suggest that IFN-gamma has the potential to protect the human mesothelial cell layers against tumor cells. PMID- 1451348 TI - A murine model of intracranial invasion: morphological observations on central nervous system invasion by murine melanoma cells. AB - We describe a model of tumour invasion in which murine melanoma/lymphocyte hybrid cells are injected into the lateral ventricle of neonatal mice. CSF circulation carries cells to the third ventricle where attachment to the ependyma and invasion of the underlying brain may be observed. At this distance from the injection site, invasion can be studied free from trauma or inflammation induced by the injection procedure. Accordingly we restricted our attention to the third ventricle. Our results reveal an unusual form of tumour invasion of the ependyma characterized by progressive attenuation of the ependymal cell layer immediately beneath tumour cell aggregates. Continuity of the ependymal cell layer is ultimately lost at a focal point immediately beneath the tumour, permitting direct contact between tumour cells and the neuropil. Subsequent deep invasion of the brain parenchyma is accomplished by pericapillary infiltration. PMID- 1451349 TI - Urokinase-type plasminogen activator activity increases during the growth of two murine mammary adenocarcinomas with different metastasizing abilities. AB - Urokinase-type plasminogen activator (u-PA) plays an important role in tumor growth and metastasis. The aim of this work was to study the u-PA production, in vitro and in vivo, in a transplantable murine mammary adenocarcinoma (M3), moderately metastatic to lung, and in a related tumor variant (MM3), highly metastatic to the same organ, during tumor development. At different times post transplantation, tumors were employed to prepare either primary cell cultures or homogenates. PA activity from conditioned media (CM), cell lysates (CLs) and tumor homogenates (THs) was quantitated by means of a fibrinolytic assay. Immunoneutralization and zymographic assays were performed to identify the PA present in both tumors. PA activity in CM, CLs and THs, that was undetectable at early stages, increased significantly along the growth of M3 adenocarcinoma. Secreted PA activity in MM3 CM was measurable at early stages and consistently increased up to 37 days post-transplantation, but a marked fall of activity was found at 48 days. PA activity in MM3 THs exhibited the same enhancement and late fall found in vitro. A positive correlation was observed between tumor size and THs PA values in both tumors. The PA present in cell cultures and THs was identified as of the u-PA type. These results support the hypothesis that high u PA levels are important for tumor invasion and that the stage of tumor development is a critical factor in their PA activity. PMID- 1451350 TI - A quantitative model for spontaneous bone metastasis: evidence for a mitogenic effect of bone on Walker 256 cancer cells. AB - A new model for the study of spontaneous bone metastasis has been developed which allows for the quantification of metastatic tumor burden and cancer cell growth rate, and which describes the progressive changes in bone morphology. Walker 256 (W256) cells or vehicle were injected into the left upper thigh muscle of male Fischer rats, which were killed 7, 10 or 14 days later. By day 7, metastases had appeared in the distal femur, in the glomeruli of the kidney, and diffusely throughout the liver and lungs. The extent of tumor burden in these organs increased over time. In the femur, 14 days of tumor burden was associated with a 53 +/- 10% decrease in trabecular bone content, a 61 +/- 15% increase in osteoclast surface, and a 95 +/- 10% decrease in osteoblast surface, as compared with non-tumor-bearing controls. By autoradiography, metastatic tumor cells in all organs were determined to have greater growth rates than did cells in the primary tumor. However, within the femur, W256 cells located adjacent to trabecular bone surfaces had a 33 +/- 7% greater growth rate than did W256 cells located > 50 microns from bone surfaces (P < 0.05), suggesting a mitogenic effect of bone. PMID- 1451351 TI - Stimulation of bone resorption results in a selective increase in the growth rate of spontaneously metastatic Walker 256 cancer cells in bone. AB - To test the hypothesis that bone metastasis is related to the rate of bone remodeling, we have examined the effect of enhanced bone resorption on the growth of spontaneously metastatic Walker 256 (W256) cancer cells. Bone resorption was stimulated in male Fischer rats by injecting Rice H-500 Leydig tumor cells subcutaneously. The resorptive response of the skeleton was confirmed in a pilot study by evaluating parameters of bone morphometry after 4, 7 and 10 days of tumor burden. The distal femoral epiphyses had 35 +/- 10% more osteoclast surface, 83 +/- 11% less osteoblast surface, and 46 +/- 5% less trabecular bone after 10 days of tumor burden, compared to non-tumor-bearing controls. To evaluate the effect of Leydig tumor-induced bone resorption on the growth response of W256 cells, 20 rats were injected intramuscularly with 2 x 10(7) W256 cells, and 20 rats were vehicle-injected. Two days later, 10 rats from each group were injected subcutaneously with Leydig tumor cells. Twelve days after W256/vehicle injection, rats were injected with [3H]thymidine, killed 2 h later, and their femurs, liver, lungs and kidneys were processed for histology. In rats injected with Leydig tumor cells only, enhanced bone resorption was confirmed by a 40 +/- 4% increase in serum calcium concentration, a 48 +/- 8% decrease in trabecular bone content, and a 72 +/- 15% decrease in osteoblast surface, compared with non-tumor-bearing rats. Metastatic W256 cells adjacent to trabecular bone in Leydig tumor-bearing rats had a 56 +/- 18% greater relative [3H]thymidine labeling index (TdR) than did W256 cells in the bones of non-Leydig tumor-bearing rats. The TdRs of W256 cells in the liver, lungs, and kidneys were not affected by Leydig tumor burden. In this model, enhanced bone resorption was associated with the selective growth promotion of metastatic W256 cells in bone, suggesting the existence of a bone-derived factor which is mitogenic to W256 cells. PMID- 1451352 TI - Patterning of B16 melanoma metastasis and colonization generally relates to tumor cell growth-stimulating or growth-inhibiting effects of organs and tissues. AB - The mouse B16 melanoma metastasizes first to the lungs and secondarily to systemic sites, involving mainly the adrenals, ovaries and pancreas. Systemic colonization effected by intracardiac injection of tumor cells establishes similar patterning, but in addition frequently colonizes the bones. To assess possible systemic site influences on metastasis and colony formation, the capacity of B16 melanoma cells to proliferate in these sites in vivo and in ex vivo explants following intracardiac injection was examined. Effects of cells isolated from these sites, and of organ- or tissue-conditioned medium, on growth of B16 cells in monolayer culture were also studied. Injected fluorochrome labeled tumor cells initially distributed without site preference, but within 48 h had begun proliferating in the adrenals, ovaries and lungs, while remaining static in the pancreas and bones, and disappearing from the spleen, liver, kidneys, brain, and skeletal muscles. Mitogenic activity releasable in soluble form was associated with all favorable organs and tissues and was the predominant influence of those tissues on cultured tumor cells. In contrast, the overall effects of liver, spleen, kidney, and brain tissues were to inhibit tumor cell growth. Soluble growth-promoting activity enhanced clonogenic growth of isolated tumor cells stimulated by mouse serum, suggesting that metastasis or colony formation might be stimulated in favorable sites by those factors together with blood-borne growth factors. The observed effects of organ- and tissue-derived cells and soluble factors on tumor cells generally reflected the in vivo consequences of tumor cell entrapment in the corresponding sites. However, the failure of metastases to develop in the bones, which are favorable sites for colonization by the same cells, remains puzzling. PMID- 1451353 TI - Combination of interleukin-2 and irradiation in therapy of murine tumors. AB - Experiments were designed to investigate the therapeutic efficacy of interleukin 2 (IL-2) combined with radiotherapy. The effect of IL-2 and local thoracic irradiation (LTI) was determined on 4-day-old lung micrometastases, generated by i.v. injection of tumor cells into mice. IL-2 alone reduced the number of lung nodules more effectively when given from 1 to 4 than 4 to 7 days after tumor cell injection. The combination of IL-2 and LTI reduced the number of lung nodules more than did the individual treatments alone. When IL-2 therapy was combined with local irradiation of 8-mm leg tumors, there was no change in the TCD50 (radiation dose yielding 50% local tumor control). However, the combination of IL 2 treatment on days 1-4 with irradiation of tumor-bearing legs on day 1 after inoculation of tumor cells reduced the TCD50 by a factor of 1.3. These results show that IL-2 improves tumor radiotherapy, but that the improvement depends on anatomic localization and tumor size at the time of treatment. PMID- 1451354 TI - What is obstetric ethics? PMID- 1451355 TI - The beginning of human life: medical observations and ethical reflections. PMID- 1451356 TI - Maternal-fetal conflict: positions and principles. PMID- 1451357 TI - Legal dimensions of maternal-fetal conflict. PMID- 1451358 TI - Assisted reproduction. PMID- 1451359 TI - Ethical issues in obstetric ultrasonography. PMID- 1451360 TI - Ethics in reproductive genetics. PMID- 1451361 TI - The abortion debate: can this chronic public illness be cured? PMID- 1451362 TI - An ethical framework for managing fetal anomalies in the third trimester. PMID- 1451363 TI - Ethical challenges in medical care for the pregnant substance abuser. PMID- 1451364 TI - Human immunodeficiency virus infection during pregnancy. PMID- 1451365 TI - Anencephalic infants as organ donors. PMID- 1451366 TI - The substantive ethics of clinical trials. PMID- 1451367 TI - The teaching of biomedical ethics in obstetrics and gynecology residency programs. PMID- 1451369 TI - Making a decision to perform a hysterectomy. PMID- 1451368 TI - Contraception for the transitional years of women older than 40 years of age. PMID- 1451370 TI - Estrogens and progestins: what to use and how to use it. PMID- 1451371 TI - Alternatives to estrogen for menopausal symptoms. AB - It is not within the scope of this chapter to discuss the long-term effects of menopause, such as osteoporosis or heart disease, or to disentangle the complex psychosocial complications and treatments of menopausal mood disorders. All long term consequences of hypoestrogenism are more amenable to prevention than to cure, as are all the negative consequences of aging. Women should maintain regular physical activity, consume a diet low in fat and high in fiber, ensure adequate calcium intake, and possibly lower animal protein consumption. Moreover, they should know their cholesterol levels and undergo regular physical examinations with an emphasis on health maintenance. Despite the many advantages of estrogen replacement therapy, it is not appropriate for all women. Cultural, personal, and medical considerations may eliminate the use of estrogen, in which case it is important to offer alternative medical advice and direction to minimize bothersome symptoms of menopause and enhance the quality of life. PMID- 1451372 TI - Estrogen replacement and heart disease. PMID- 1451373 TI - Perspectives on osteoporosis. AB - The goal of this chapter was to provide enough information so that the following questions could be answered in a clinical context: 1. Does the patient have osteoporosis or a risk for it? Is densitometry needed? 2. Why does the patient have osteoporosis? Is the diagnosis "the tip of the iceberg" because of an occult secondary cause? 3. Is the patient receiving adequate calcium? Can the patient benefit from estrogen? 4. What clinical information or tests are required to follow a patient with osteoporosis? 5. What drugs are indicated for osteoporosis? Which are promising and which require further research? PMID- 1451374 TI - Hormonal management of osteoporosis. PMID- 1451375 TI - Menopause: a normal view. PMID- 1451376 TI - The carboxyhemoglobin method for estimating bilirubin production in neonates. Japanese studies. PMID- 1451377 TI - Hyperbilirubinemia in black infants. Role of glucose-6-phosphate dehydrogenase deficiency. PMID- 1451378 TI - Jaundice in Navajo neonates. PMID- 1451379 TI - Racial differences in neonatal jaundice. Hyperbilirubinemia in Hispanic infants- a survey. PMID- 1451380 TI - Human growth hormone: a new substance of abuse among adolescents? AB - It has been estimated that as many as 250,000 adolescents are using anabolic steroids (AS). Recently, anecdotal reports suggest that athletes may also be using human growth hormone (HGH). The purpose of the present study was to determine the following: 1) if adolescents in two suburban midwestern high schools (83% white, 14% Asian, and 3% black) were using HGH; 2) knowledge of its effects; 3) reasons for use; and 4) concurrent AS use. After we obtained informed written consent, 224 male and 208 female 10th-grade students were surveyed using a 15-item questionnaire. Of male students surveyed, 5% (n = 11) reported past or present use of HGH, and one female student reported use. Our data suggest that among male adolescents surveyed, a majority had heard of this substance, and 31% of males reported knowing someone who was using HGH. Chi-square analysis found a significant association between AS and HGH use where seven AS users reported past or present use of HGH. Most HGH users were unaware of its side effects and reported first use between 14 and 15 years of age. No differences in sports activity, ethnicity, or age were found between users and nonusers of HGH. PMID- 1451381 TI - Early childhood tooth decay. Pediatric interventions. AB - Pediatricians in the greater Chicago area were surveyed to probe their awareness and approaches to management of dental caries in early childhood. A total of 298 pediatricians (21% of those surveyed) responded to the questionnaire. Ninety-five percent of the respondents stated they examined their patients' teeth; 85% considered dental examinations part of their responsibility for children under 3 years of age. However, our data suggest that many pediatricians are unaware of the decay and the dietary patterns associated with tooth decay in early childhood. Although 96% of the respondents referred patients to a dentist when decay was diagnosed, analysis of diet and dietary counseling were performed by only 61% and 65% of the respondents, respectively. Recommendations for preventive measures that can be adopted by pediatricians are offered. PMID- 1451382 TI - Behavioral correlates of caffeine consumption by children. PMID- 1451383 TI - A computerized automatic exposure device for chest radiography in infants. PMID- 1451384 TI - Late presentation of a subglottic hemangioma masquerading as asthma. PMID- 1451385 TI - Gentian violet toxicity. PMID- 1451386 TI - Accidental intravenous administration of semi-elemental formula in an infant. PMID- 1451387 TI - Good news for health promotion in schools. PMID- 1451388 TI - Decade of the Child in Colorado. PMID- 1451389 TI - Recommendations for assessing children's lead exposure and screening for lead poisoning. PMID- 1451390 TI - Prevention of low birthweight births by reduction of behavioral risks during pregnancy. PMID- 1451391 TI - Additional changes to immunization requirements. PMID- 1451392 TI - Medical training in Costa Rica. PMID- 1451393 TI - Colorado National Guard doctors in Latin America. PMID- 1451394 TI - Americans with Disabilities Act: steps toward compliance. PMID- 1451395 TI - Abraham Lincoln: malpractice defense attorney. PMID- 1451396 TI - Intra-ocular haemorrhage, a frequent complication of acute promyelocytic leukaemia. AB - We have found a high incidence of ocular haemorrhage in patients with acute promyelocytic leukaemia (APL). We describe a series of seven consecutive cases of APL, five of which developed ocular haemorrhage. There were no consistent detectable abnormalities in coagulation predictive of ocular damage. Ocular haemorrhage occurred despite the use of aggressive blood product support and its incidence was not altered by the use of the anti fibrinolytic agent tranexamic acid or by the use of heparin. Complete spontaneous resolution of the ocular pathology occurred in three of the five cases of ocular haemorrhage and partial recovery occurred in one. The fifth patient required surgical intervention. The mechanisms underlying the coagulopathy associated with APL are poorly understood. We discuss the evidence in support of primary disseminated intravascular coagulation and primary fibrinolysis. A logical approach to the management of the bleeding complications in APL can only follow greater understanding of the underlying pathophysiology. PMID- 1451397 TI - Haematological splenectomy. Changing indications and complications. AB - Review of splenectomies carried out for haematological disease over a ten-year period, at a district hospital, shows that the indications for splenectomy have changed substantially over this time. Fewer patients with idiopathic thrombocytopenic purpura now require splenectomy, however its role in the management of lymphoproliferative disorders has expanded. Splenectomy remains an important therapeutic option for a range of haematological disorders: this series shows it to be a safe and effective operation in selected patients, although it is not without both short and long-term sequelae. PMID- 1451398 TI - Evans syndrome: a report on 12 patients. AB - From 1981 to 1989, 12 patients of the University Hospital, Kuala Lumpur, were diagnosed to have Evans syndrome based on direct antiglobulin test (DAT) positive haemolytic anaemia and immune thrombocytopenia occurring either simultaneously (7 patients) or consecutively (5 patients). Their mean age at presentation was 24.8 years with a marked female preponderance. All 12 patients were given high dose steroid after diagnosis. Subsequently, other modalities including intravenous immunoglobulin (1 patient) and high dose methylprednisolone (1 patient) were given. Three patients died of intracranial haemorrhage during the first admission while 1 patient died of pulmonary embolism six months after diagnosis. Three patients had splenectomy because of thrombocytopenia. Six patients tested positive for antinuclear factor and antibodies to double stranded DNA and four of them died. Positive serology appeared to be associated with a poorer prognosis. Follow up observations indicate that patients who survive the acute attacks fare reasonably well. PMID- 1451400 TI - The haemodynamic responses to venesection and the effects of cardiovascular disease. AB - The haemodynamic effects of the venesection of one unit (450 ml) of blood over 9 min were measured using non-invasive techniques, in 14 healthy controls and 18 patients with coronary heart disease or hypertension. Venesection was associated with significant reductions in supine and standing systolic and diastolic blood pressure, stroke volume index and cardiac index, and increases in standing heart rate, in both patient groups. No significant differences were observed between the responses of subjects with and without cardiovascular disease. The authors conclude that, in contrast to established teaching, blood loss can be detected in its early stages by careful haemodynamic monitoring and that venesection can be performed safely without volume replacement in patients with stable cardiovascular disease. PMID- 1451399 TI - Venesection in haemoglobin Yakima, a high oxygen affinity haemoglobin. AB - High oxygen affinity haemoglobins result in polycythaemia and cardiovascular adaptation to maintain tissue oxygenation. The polycythaemia can cause symptoms of hyperviscosity and vaso-occlusive disease. We report a kindred with a high affinity haemoglobin (Haemoglobin Yakima) one of whose members gave birth to two infants with intra-uterine growth retardation and who suffered with symptoms of hyperviscosity which settled on reduction of the PCV by venesection. PMID- 1451401 TI - Ultrastructure of the bone marrow in HIV infection: evidence of dyshaemopoiesis and stromal cell damage. AB - The ultrastructure of bone marrow cells was studied in nine patients infected with the human immunodeficiency virus (HIV). Two of these (cases 1 and 3) were thrombocytopenic, had never suffered from opportunistic infections and had not received any drugs prior to the time of study. A number of ultrastructural abnormalities were found in a variable proportion of the affected cell types in all nine patients. These were: (a) an increased prevalence of multivesicular bodies within several cell types and of abnormalities of the nuclear membrane in neutrophil granulocytes, (b) an increase in the size of the Golgi apparatus and in the quantity of endoplasmic reticulum in neutrophil granulocytes, (c) dysplastic features, including multiple long intranuclear clefts and large cytoplasmic vacuoles in some erythroblasts and (d) vacuolation of the plasma cells. Other abnormalities seen in a proportion of the patients were: (a) cylindrical confronting cisternae (CCC) in some of the lymphocytes, macrophages (phagocytic reticular cells), non-phagocytic reticular cells (including adventitial cells) and endothelial cells of marrow sinusoids, (b) tubuloreticular structures (TRS) in some lymphocytes, plasma cells, monocytes and endothelial cells and (c) precipitates of protein within occasional erythroblasts and marrow reticulocytes. There was also a striking and hitherto undescribed abnormality of the structure of the nucleus in intersinusoidal and perisinusoidal non-phagocytic reticular cells. This was seen in six patients, including case 3, and was characterized by the extensive detachment of masses of abnormally electron-dense heterochromatin from the nuclear membrane, the presence of a uniformly thin layer of electron-dense material at the inner surface of the areas of nuclear membrane denuded of heterochromatin masses and an abnormal electron lucency of areas containing euchromatin. The CCC and TRS were found in the six patients with the lowest number of circulating CD4-positive T cells. The precipitation of protein within erythroid cells may have been caused by the oxidant effect of dapsone or high doses of co-trimoxazole. The abnormalities in the stromal cells and in particular the nuclear changes seen in the non-phagocytic reticular cells support the possibility that one of the mechanisms underlying the cytopenia in patients infected with HIV may be a disturbance of the microenvironmental regulation of haemopoiesis. PMID- 1451402 TI - Measurement of whole blood phagocyte chemiluminescence in a microtitreplate format. AB - Zymosan-induced luminol-enhanced chemiluminescence of phagocytes was measured in whole blood using a microtitreplate format. A consistent reaction response curve could be obtained using a normal blood sample, with low intra-assay variations in peak light index, cumulated response as well as time taken to reach the peak. Variations were common when tests were done on different days for the same individual, or when different persons were compared simultaneously. Reactions were hastened and enhanced if continuous shaking at 37 degrees C was applied. The interval between time zero and peak was the most consistent variable, with a coefficient of variation of 12% in inter-assay analysis. Because of its simplicity and ease of operation, the method is potentially useful in studying phagocyte functions in pathological states. PMID- 1451403 TI - Spurious platelet counts in acute leukaemia with DIC due to cell fragmentation. AB - Automated platelet counts in a patient with newly diagnosed AML M5 with extreme leukocytosis were reported as 129, 166 and 121 x 10(9)/1. Routine blood films showed a corresponding number of platelet-sized particles, judged to be platelets. The patient was treated for DIC with low-dose heparin infusion. Platelet transfusions were not given initially. The patient died 14 h after admission from intracerebral haematoma. The origin of the platelet-sized particles seen in routine stained blood films was examined by cytochemical and immunological staining for peroxidase, non-specific esterase, CD 13 and CD 33. About 1/3 of the fragments had the same staining characteristics as the leukaemia cells, indicating leukaemia cell origin. Staining for platelet-specific antigen GpIIIa was positive only in 4% of the platelet-sized fragments, with a calculated true platelet count of 4 x 10(9)/1. The presence of cell fragments masquerading as platelets should be suspected in leukaemia patients with bleeding symptoms and normal or near normal platelet counts. PMID- 1451404 TI - A mainframe interfacing computer management system for the control of oral anticoagulant therapy. AB - A unique computerized management system has been used to control the anticoagulation of over 400 patients at a large teaching hospital for the last eighteen months. The system is located on the main pathology computer which can be interfaced with the patient administration system (PAS). This enables files in the anticoagulant program to be linked with files in the PAS and files in the haematology database. This system has many advantages over a stand-alone microcomputer system and will form the basis for the next generation of computerized anticoagulant management systems. PMID- 1451405 TI - High Eo-CSF activity in T-cell non-Hodgkin's lymphoma with eosinophilia. PMID- 1451406 TI - Hodgkin's disease and paraproteinaemia: a case report and review of the literature. PMID- 1451407 TI - Spurious anoxaemia in a patient with chronic myeloid leukaemia. PMID- 1451408 TI - Interphase cytogenetic analysis of non-Hodgkin's lymphoma. PMID- 1451409 TI - Which tests are most useful in distinguishing between reactive thrombocytosis and the thrombocytosis of myeloproliferative disease? PMID- 1451410 TI - Use of the Technicon H1 hypochromia flag in detecting spurious macrocytosis induced by excessive K2-EDTA concentration. PMID- 1451411 TI - Monocyte counts on the Coulter STKS. PMID- 1451412 TI - Discourse influences during parsing are delayed. AB - Subjects read sentences containing either a syntactically ambiguous prepositional phrase attachment or a syntactically ambiguous reduced relative clause. The sentences were embedded in passages of text that were consistent with either the minimal or non-minimal attachment reading. In addition, a discourse factor (i.e., whether or not the target sentence was in the discourse focus) was varied. Subjects' eye movements were recorded as they read the passages of text. Our primary finding was that subjects were garden-pathed even when there was biasing context. However, when the target sentence was in the discourse focus, subjects were able to recover more readily from their initial erroneous parse of the sentence. The data thus support models of sentence parsing that postulate that the parsing of a sentence is based upon structurally based principles and the influence of semantic or pragmatic information makes itself felt only after the initial parsing decision has been made. PMID- 1451413 TI - Wishful thinking impairs belief-desire reasoning: a case of decoupling failure in adults? AB - Subjects were presented with a scenario that described how a certain type of opinion poll can be manipulated by respondents to put one particular political party (the threatened party) at a disadvantage. In a first experiment, people supporting this party but pretending to oppose it were found to be as likely to say that they would manipulate the poll as people who actually opposed it. In a second experiment, the threat embodied in the scenario was made more direct. It was also more salient because the study was carried out at a time of heightened political awareness when supporters of the threatened party were genuinely concerned about its future. People supporting the threatened party but pretending to oppose it were now about half as likely to say that they would manipulate the poll as those who actually opposed it. Two explanations for this breakdown in the belief-desire reasoning subserving pretense are considered. PMID- 1451414 TI - Using children's humor to clarify the relationship between linguistic awareness and early reading ability. AB - This study uses linguistic humor to show that an awareness of only those linguistic units transcribed by the orthography bears a special relation to early reading success. The subjects were 48 second-grade children tested on ten "phoneme/morpheme" riddles which manipulate phonemes and bound morphemes and ten "control" riddles which depend on awareness of other aspects of linguistic structure and "common sense". Each child also received the Word Identification and Word Attack subtests of the Woodcock Reading Mastery Tests and the Peabody Picture Vocabulary Test. Reading ability was significantly related to correct resolution of the phoneme/morpheme riddles but not to correct resolution of the control riddles. PPVT scores were significantly related to performance on both types of riddles but not to reading ability. Thus, while IQ is related to the resolution of riddles in general, reading ability has a special relation to riddles which manipulate phonemes and morphemes, consistent with the morphophonological nature of English orthography. PMID- 1451415 TI - Sexual segregation in squirrel monkeys (Saimiri sciureus): a transactional analysis of adult social dynamics. AB - Female agonism against males and male interventions in social transactions between the sexes are 2 explanations for the low rates of social engagement observed between male and female squirrel monkeys (Saimiri sciureus). These possibilities were evaluated by comparing the frequency, structure, and content of transactions between the sexes in 3 experimental social units: male-female pairs, single-male-multifemale groups, and multimale-multifemale groups. Affiliative transactions between the sexes occurred 3-5 times less often in multimale-multifemale groups than in male-female pairs and in single-male multifemale groups. Intermale agonism in the multimale-multifemale groups often coincided with ongoing transactions between the sexes, whereas female agonism against males was rather uncommon in all social units. The results failed to support the female agonism hypothesis and indicate a need for more detailed studies of intermale social dynamics. PMID- 1451416 TI - Transitive inference in rats (Rattus norvegicus). AB - Although Piagetian theory proposes that the ability to make transitive inferences is confined to humans above age 7, recent evidence has suggested that this logical ability may be more broad based. In nonverbal tests, transitive inference has been demonstrated in preschool children and 2 species of nonhuman primates. In these experiments, I demonstrate evidence of transitive inference in rats (Rattus norvegicus). I used an ordered series of 5 olfactory stimuli (A < B < C < D < E) from which correct inferences were made about the novel B versus D pair. Control procedures indicated that performance did not depend on the recency with which the correct answer was rewarded during training and may be disrupted by the addition of logically inconsistent premises (F > E and A > F). The possibility that logical transitivity may reflect a form of spatial paralogic rather than formal deductions from a syllogistic-verbal system is discussed. PMID- 1451417 TI - Silhouettes elicit alarm calls from captive vervet monkeys (Cercopithecus aethiops). AB - In Part 1, we analyzed alarm calls produced by captive vervets (Cercopithecus aethiops) in response to naturally occurring stimuli. Females and juveniles regularly alarm called to airplanes, birds, and barking dogs. Juvenile females accounted for 60% of these alarm calls. In Part 2, we isolated several monkeys from the colony and presented them with life-sized silhouettes of a leopard, snake, eagle, baboon, vervet, and goose. Adult monkeys alarm called more than did juveniles. Alarm calls were elicited by leopard, snake, baboon, and vervet silhouettes, but none were elicited by eagle or goose silhouettes. Some leopard and snake alarm calls matched those recorded in the wild in the context of the vervets' natural predators. Results indicate that silhouette stimuli are a useful technique for eliciting monkey vocalizations in the laboratory. PMID- 1451418 TI - Rodent ultrasonic short calls: locomotion, biomechanics, and communication. AB - Rodents of many species emit short ultrasonic vocalizations during copulation, aggression, and other activities. Thiessen and Kittrell (1979) hypothesized that ultrasound emission by gerbils is the acoustic by-product of physical compression of the thorax during certain locomotor behaviors. I carry this hypothesis further by relating gerbil ultrasound to the biomechanics of respiration during locomotion. I also suggest that at least some of the ultrasonic emissions of other rodent species are, like the gerbil's, by-products of thoracic compression during locomotion. Support for this suggestion comes from descriptions in the literature of ultrasound emission as well as slow-motion analysis of rat copulatory behavior. Finally, this alternative view of rodent ultrasound has consequences for the interpretation of experimental findings in ultrasound research and for the understanding of messages and meanings in rodent communication. PMID- 1451419 TI - Estrus induction in four species of voles (Microtus). AB - Male-induced estrus was examined in montane (Microtus montanus), meadow (M. pennsylvanicus), prairie (M. ochrogaster), and pine (M. pinetorum) voles. Duration of male contact needed for receptivity, effects of parity, and vaginal cytology were assessed. Among nulliparous females, montane voles attained receptivity with less male contact than prairie voles. Meadow and pine voles showed very low receptivity rates. Among parous females, montane and meadow voles did not differ in duration of male contact needed for receptivity and required less than prairie voles. Overall, parous females had higher receptivity rates than nulliparous females. When isolated from males, prairie and pine voles had more leukocytes and fewer cornified cells in vaginal smears than montane or meadow voles. Species differences in estrus induction are discussed in relation to species differences in social organization. PMID- 1451420 TI - Loudness bisection and masking in the rat (Rattus norvegicus). AB - The bisection method of animal psychophysical scaling was examined as a measurement procedure. The critical assumptions of bisection scaling, as described by Pfanzagl (1968), were tested to determine if a valid equal-interval scale could be derived. A valid scale was derived in which loudness for the rat (Rattus norvegicus; n = 13) was a power function of sound pressure for 4-kHz tones. Masking noise reduced the discriminability of tonal stimuli but did not affect the bisection point. This result is consistent with an interval scale representation of loudness and demonstrates scale meaningfulness. Loudness bisection data that have been reported in the literature for 3 species (humans, rats, and pigeons) are in substantial agreement with our results. PMID- 1451421 TI - Ejaculate disruption in two species of voles (Microtus): on the PEI matching law. AB - We permitted male prairie and montane voles (Microtus ochrogaster and M. montanus) five thrusts, without ejaculation, with a female at variable times after a 1st male ejaculated. In both prairie and montane voles, there were fewer sperm, in relation to control conditions, in the female's tract 1 hr after ejaculation if the female received thrusts immediately or 15 min after the ejaculate. There was no such effect after a 50-min delay. There was no significant decrease in litter production in prairie voles caused by thrusts delivered either immediately or after a 15-min delay. Sperm transport in these species is susceptible to disruption for a longer period than in deer mice or rats. The proposal that the postejaculatory interval protects a male from disrupting its own sperm transport (the PEI matching law) appears not to hold for these species. PMID- 1451422 TI - Behavioral asymmetries of psychomotor performance in rhesus monkeys (Macaca mulatta): a dissociation between hand preference and skill. AB - Hand preferences were recorded for 35 rhesus monkeys (Macaca mulatta) as they manipulated a joystick in response to 2 computerized tasks. These preferences were then used to contrast 8 left- and 10 right-handed subjects on performance measures of hand skill. Individual hand preferences were found, but no significant population asymmetry was observed across the sample. However, the performance data reveal substantial benefits of right-handedness for joystick manipulation, as this group of monkeys mastered the 2 psychomotor tasks significantly faster than did their left-handed counterparts. The data support earlier reports of a right-hand advantage for joystick manipulation and also support the importance of distinguishing between hand preference and manual performance in research on functional asymmetries. PMID- 1451423 TI - Object manipulation and the use of tools by infant baboons (Papio cynocephalus anubis). AB - Infant baboons (Papio cynocephalus anubis) in a captive peer group used objects as containers, drinking utensils, and sponges in the context of play. The baboons later used paper, browse, and other materials as tools to extract sweet liquids from apparatus designed to accommodate sponging and probing behavior. The results of this study demonstrate flexible combinatorial manipulation and spontaneous use of tools by infant baboons. These data are consistent with hypotheses that (a) an evolutionary history of omnivorous extractive foraging is associated with the use of tools and (b) free play in an object-enriched captive environment may facilitate combinatorial manipulation in nonhuman primates. PMID- 1451424 TI - Object permanence in cats (Felis catus): an ecological approach to the study of invisible displacements. AB - A single invisible displacement object permanence task was administered to 19 cats (Felis catus). In this task, cats watched a target object from behind a transparent panel. However, cats had to walk around an opaque panel to reach the object. While cats were behind the opaque panel, the object was hidden behind one of two screens. As cats did not perceive the disappearance of the object behind the target screen, the object was invisibly hidden. Results showed that cats solved this task with great flexibility, which markedly contrasts with what has been observed in previous research. The discussion emphasizes the difference between the typical Piagetian task in which the information necessary to succeed must be dealt with in retrospective way, whereas in our task cats had to anticipate a new position of the object. The ecological relevance of this new task is also discussed. PMID- 1451425 TI - Rats (Rattus norvegicus) modulate eating speed and vigilance to optimize food consumption: effects of cover, circadian rhythm, food deprivation, and individual differences. AB - The eating behavior of rats (Rattus norvegicus) given food pellets of specified size was examined as a function of environmental, circadian, and experiential influences. Eating times were shorter in lighted, exposed environments than in dark, covered environments, even though in novel, exposed conditions the rats made many scanning movements as they ate. Eating time also varied as a function of the circadian cycle in that eating times were shorter in the night portion of the day-night cycle. Finally, eating times decreased if rats were food deprived, and deprivation had a small but enduring influence. Within the tests there were differences in the eating times of individual rats that were not attributable to the experimental manipulations. That rats can optimize food intake by varying eating speed is discussed in relation to physiological regulation of feeding and to optimal foraging theory. PMID- 1451426 TI - The Drosophila genome project: current status of the physical map. PMID- 1451427 TI - Glycerolipid biosynthesis in adipose tissue of the bovine during growth. AB - 1. Rates of palmitate esterification in tissue slices and glycerophosphate acyltransferase activity in homogenates were determined in bovine subcutaneous and intermuscular adipose tissue at 340, 418 or 498 kg of live weight. 2. Lower rib section fat accretion rates were observed from 340 to 418 kg than from 418 to 498 kg. 3. Changes in palmitate esterification rates at different body weights were consistent with reduced rib section fat accretion as well as with reported differences in fat accretion in subcutaneous and intermuscular fat depots. 4. Glycerophosphate acyltransferase activity was increased at 418 kg and remained elevated whereas palmitate esterification was decreased at 418 and then increased at 498 kg. 5. Differences between palmitate esterification and glycerophosphate acyltransferase in vitro may have been related to differences in substrate supply. PMID- 1451428 TI - Intestinal disaccharidases in five species of phyllostomoid bats. AB - 1. Intestinal disaccharidases were studied in nectarivorous (Leptonycteris curasoae and Glossophaga soricina), frugivorous (Artibeus jamaicensis and Sturnira lilium), and insectivorous (Pteronotus personatus) adult bats. 2. Adult bats lacked measurable lactase activity. With the exception of trehalase activity, which was present only in P. personatus, nectar- and fruit-eating bats exhibited higher disaccharidase activities standardized by intestinal nominal area than insect-eating P. personatus. 3. Maltase and sucrase activities were significantly linearly correlated. 4. Apparent affinity of sucrase varied almost 5-fold among species. This variation may reflect unstirred layer effects resulting from sucrase being a membrane bound enzyme rather than differences in the "true" affinity of sucrase in solution. 5. Passerine birds showed higher maltase activity per unit of sucrase activity than bats and hummingbirds. Maximal sucrase and maltase activities standardized per intestinal nominal area are 1.5-2 times higher in hummingbirds than in nectar-feeding bats. PMID- 1451429 TI - Changes in apyrase activity in uterus and mammary gland during the lactogenic cycle. AB - 1. The purpose of this present research was to explore the possible roles of ATP diphosphohydrolase (apyrase) in two tissues with high energetic demands during cell proliferation and differentiation. 2. Changes in apyrase activities during the pregnancy lactation cycle were examined in the rat uterus and mammary gland. 3. A significant decrease in apyrase activity (ATPase-ADPase) was observed in the pregnant uterus; this observation correlates with a minor inhibitory effect on platelet aggregation. 4. In mammary gland, the enzyme activity increases during lactation in parallel with an increase in blood supply, synthesis of glycoproteins and cell proliferation. 5. Apyrase activity did not change during the estrous cycle. Estradiol administration to rats slightly increased (20%) both ATPase-ADPase activities. 6. The probable function of apyrase is finally discussed, based on its substrate specificity and subcellular localization. PMID- 1451430 TI - Small nuclear ribonucleoprotein polypeptides in rat sperm. AB - 1. Immunoblot analysis of rat sperm head proteins revealed the presence of polypeptides recognized by anti-Sm serum obtained from patients with systemic lupus erythematosus. 2. Two of these polypeptides have molecular weights of 26,000 and 15,000 and they were identified as small nuclear ribonucleoprotein components present in other rat tissues. 3. When the autoimmune serum was used in the immuno-gold procedure for electron microscopy, gold particles were found only on the sperm nucleus. 4. The results indicate that some polypeptides of the small nuclear ribonucleoprotein complex are components of the rat sperm chromatin. PMID- 1451431 TI - Apparent deficiency of metallothionein in the liver of the Antarctic icefish Chionodraco hamatus. Identification and isolation of a zinc-containing protein unlike metallothionein. AB - 1. A zinc-binding protein has been isolated and purified from the liver of the icefish Chionodraco hamatus. 2. The icefish Zn-protein has characteristics distinct from those of metallothionein. 3. The amino acid composition shows a low content of cysteine and a high content of glutamate and aspartate. 4. No metallothionein has been detected in the extracts from icefish liver. PMID- 1451432 TI - Progesterone stimulates prostaglandin synthesis in eggshell gland mucosa of estrogen-primed chickens. AB - 1. Prostaglandins may be involved in calcium translocation in the avian shell gland, since indomethacin, administered at the beginning of shell formation, reduces eggshell thickness as well as 45Ca-uptake and prostaglandin synthesis by a homogenate of eggshell gland mucosa. 2. The stimulus for calcium transport in the shell gland during shell formation remains unknown. 3. The present study was undertaken to investigate the effects of progesterone on prostaglandin formation by the eggshell gland mucosa of the domestic fowl. 4. Progesterone significantly stimulated synthesis of PGF2 alpha, PGE2 and TXB2 by eggshell gland mucosa homogenate. 5. Progesterone treatment also induced the synthesis of the biotin binding protein, avidin. 6. A microsomal fraction prepared from the eggshell gland mucosa had a high affinity for binding PGE2. 7. Progesterone treatment reduced the KD value of this binding without affecting the maximal number of binding sites. 8. Progesterone did not change the total calcium content of shell gland mucosa. 9. The role progesterone plays in prostaglandin formation and calcium transport in the eggshell gland mucosa is discussed. PMID- 1451433 TI - Developmental changes of L-lysine-ketoglutarate reductase in rat brain and liver. AB - 1. Developmental aspects of L-lysine-ketoglutarate reductase, the first enzyme in saccharopine pathway of L-lysine degradation in rat liver and brain tissues were studied. 2. Although the adult rat brain shows negligible activity, the enzyme activity was shown to be highly active during the early stages of development. 3. The enzyme activity gradually decreased through development in the brain, whereas it gradually increased in the liver, establishing the fact that the saccharopine pathway is the major pathway in liver. 4. Our results also show that glucagon stimulated the induction of this enzyme by 2-3-fold in both adult liver and brain tissues. PMID- 1451434 TI - Affinity purification and characterization of CIF, an insect immunoresponsive factor with NF-kappa B-like properties. AB - 1. A rapid DNA affinity purification procedure was worked out for the purification of the Cecropia Immunoresponsive Factor (CIF) from the pupae of Hyalophora cecropia. 2. CIF consists of a single polypeptide chain of 65 kDa and is present as a homodimer under native conditions. 3. CIF binds to the kappa B like sequences upstream of the H. cecropia immune genes with the following order of affinity: attacin kappa B greater than lysozyme kappa B greater than cecropin A kappa B greater than cecropin B kappa B. 4. The purified CIF also strongly binds to the kappa B sequences from both the immunoglobulin kappa light chain gene and the MHC class I gene. 5. The DNA binding of CIF can be inhibited by antisera directed against NF-kappa B-related proteins. 6. The cytoplasmic factor Cl, co-purified from the affinity column, contains two polypeptide chains, one of which has the same molecular weight as CIF. PMID- 1451435 TI - Purification and properties of the F1-ATPase from liver mitochondria of Gallus gallus. AB - 1. This paper is the first detailed report of the purification of a mitochondrial ATPase from an avian species. 2. The Gallus gallus liver mitochondrial F1-ATPase was purified by chloroform extraction and ion-exchange chromatography. 3. The enzyme shows the five alpha, beta, tau, delta, and epsilon subunits characteristic of mitochondrial F1-ATPases. 4. The Km for ATP is 1 mM and for Mg 0.5 mM with a specific activity of 25.2 mu moles of ATP hydrolyzed x min-1 x mg 1. 5. Unlike mammals enzymes the chicken mitochondrial ATPase shows maximal activity with ITP as substrate, and is strongly inhibited by Cu. PMID- 1451436 TI - Ontogeny of DNA synthetic rhythms in chick (Gallus domesticus) liver. AB - 1. The diurnal pattern of DNA synthesis and mitotic activity in neonatal (1-4-day old) chick liver were investigated under various feeding and lighting regimens. 2. In the meal-fed chicks under the condition of light-dark cycle, DNA synthesis exhibited a 12 hr cycle; the peaks occurring at 9:00 and 21:00. 3. Fasting caused a gradual decrease in the 21:00 peaks. 4. The changes in the lighting regimen to 24 hr continuous lighting also caused a profound change in the DNA-synthetic pattern, suggesting a complex interplay of feeding and lighting regimens in the manifestation of the DNA-synthetic rhythm in neonatal chick liver. PMID- 1451437 TI - Heme biosynthesis pathway regulation in a model of hepatocarcinogenesis pre initiation. AB - 1. Heme regulation before the appearance of hyperplastic nodules was investigated in mice models of hepatocarcinogenesis. 2. With this aim 5-aminolaevulinate synthetase (ALA-S), microsomal heme-oxygenase (MHO), mitochondrial and cytoplasmic rhodanese activities were examined throughout a period of 35 days in animals exposed to dietary p-dimethylaminoazobenzene (DAB). 3. ALA-S activity was significantly diminished (50%) on day 14, then showing a sharply rising profile from day 28 onwards, and reaching 350% on day 35. 4. A similar profile was observed for mitochondrial rhodanese activity. 5. Changes in MHO and cytoplasmic rhodanese activities were almost the opposite to those observed for ALA-S. 6. The distinctive alteration in mitochondrial and cytoplasmic rhodanese would suggest that it plays a subtle role in ALA-S regulation during carcinogenesis initiation through a mechanism that appears to involve subcellular localization controls perhaps by means of the breakage of cystine trisulphide postulated to act as an ALA-S activator. 7. Taking into account the present results, we suggest a probable mechanism for the onset of hepatocarcinogenesis that includes a primary activating liver status, provoking biochemical aberration leading to the stage of initiation of hepatocarcinogenesis involving the whole organ. PMID- 1451438 TI - Presence and genetic polymorphism of an epithelial mucin in milk of the goat (Capra hircus). AB - 1. Analysis of individual samples of goat's milk by SDS-PAGE confirmed that they contain a polymorphic, high molecular weight (M(r) greater than 205 kDa) glycoprotein. 2. On SDS-gels, the polymorphism takes the form of two bands of variable mobility which usually stain with equal intensity. This polymorphism resembles that detected in milk mucins of other species and is best explained by an expression of codominant genes containing variable numbers of a tandemly repeated 60-base segment. 3. Analysis of milk fractions provided evidence that the goat mucin is exclusively a membrane protein, and that it can be purified from other fat globule proteins by gel filtration and peanut lectin affinity chromatography. 4. Among proteins in the goat milk fat globule, the mucin appears to be a strong immunogen but the resulting antibodies applied to Western blots only stained the cow's milk mucin mildly and the guinea pig and human milk mucins not at all. PMID- 1451439 TI - Correlations between the activities of semen acid phosphatase and Ca(2+) dependent ATPase and age in different breeds of cocks. AB - 1. The present work aims to find a biochemical criterion for evaluating the evolution of sperm according to age through the study of the ATPase activity from the spermatozoa and the acid phosphatase from the seminal plasma of cocks from three different breeds. 2. The optimal parameters of action of the cock semen acid phosphatase and the Ca(2+)-dependent ATPase from the spermatozoa were studied. 3. The substrate specificity of the semen acid phosphatase and its inhibition by tartrate, fluoride, metavanadate, molybdate and Hg2+ were also studied. 4. The two enzymes were determined from the Sussex, Golden Cornish and Plymouth Rock breeds at different ages. 5. The data lead to the conclusion that some properties of bird spermatozoa are less influenced by breed while the acid phosphatase activity, secreted in the ductus deferens is a breed characteristic. PMID- 1451440 TI - Selected biological activities of saraines. AB - 1. The Mediterranean sponge Reniera sarai, Pulitzeri-Finali, 1969 (Demospongiae: Haploscleridae: Renieridae) possesses in large amounts a series of unprecedented polycyclic alkaloids, saraines 1-3 and saraines A-C. 2. The structural peculiarities of saraines, their chemical-physical characteristics, along with their relevant abundance in the sponge, prompted a study aimed at investigating their biological properties. 3. Saraines were assayed for their cytotoxic, antibacterial, insecticidal and potential antitumoral activities. These results, along with the growth inhibition of fertilized sea urchin eggs, are reported. PMID- 1451441 TI - Evidence of the presence of GTPase inhibiting proteins for a low M(r) GTP-binding protein, ram p25, in rat spleen and pheochromocytoma PC12 cells. AB - 1. GTPase inhibiting activity for a low M(r) GTP-binding protein, ram p25, was detected in the cytosolic fractions of rat spleen and PC12 cells. 2. The inhibitors were heat-labile and trypsin-sensitive, indicating that they were of proteinous nature. 3. The molecular mass of the inhibitor in the spleen appeared to be about 65 kDa on the elution profile from the gel filtration column. PMID- 1451442 TI - A comparative study on defense systems for lipid peroxidation by free radicals in spontaneously hypertensive and normotensive rat myocardium. AB - 1. Antiperoxidation ability and lipid peroxidation in myocardium were examined in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) at 6 and 16 weeks of age. 2. Glutathione peroxidase activity was higher in SHR at 6 weeks of age, but lower at 16 weeks compared to that in WKY. alpha-Tocopherol content was lower in SHR at both 6 and 16 weeks of age than in WKY. 3. In vitro formation of free malondialdehyde was more pronounced in SHR myocardium than in WKY. 4. Coincidence of lower antiperoxidation ability and higher peroxidation of membrane phospholipid indicate myocardial cell vulnerability in SHR hypertrophied myocardium. PMID- 1451443 TI - Purification and characterisation of glutathione transferase from the giant African snail, Archachatina marginata. AB - 1. Glutathione-S-transferase has been purified from the hepatopancreas of Archachatina marginata to homogeneity. 2. The enzyme was found to be a dimer with a molecular weight of 44,000. The subunits sizes were 22,500 and 23,500 respectively. The isoelectric points of the enzyme were 8.35, 7.95 and 4. The enzyme was most stable at temperature below 40 degrees C. Upon denaturation by 4 M urea, only 56% of the activity could be recovered. 3. The Kms for glutathione and 1-chloro-2,4-dinitrobenze (CDNB) were 0.23 mM and 0.4 mM respectively. The specific activity of the enzyme with CDNB and p-nitrophylacetate as substrates were 47 mumol/mg and 38 mumol/mg respectively. 4. Inhibition studies showed that S-hexylglutathione, Rose Bengal, iodoacetamide, sodium azide and Procion Blue H-B were good inhibitors with I50 values ranging from 18.5 microM to 299 mM. 5. The amino acid composition showed that the enzyme had a relatively high content of hydrophobic and acidic amino acid residues. The peptide maps of the tryptic digests of the native and performic acid-oxidised enzyme indicated that there might be about two disulphide bridges per molecule of the enzyme. PMID- 1451444 TI - Changes in liver microsome lipids and plasma fatty acids induced by dietary orotate in the weanling rat. AB - 1. Dietary orotate produced a decrease in total plasma fatty acids which was reflected in low values of saturated, monounsaturated and polyunsaturated fatty acids longer than 18 carbon atoms of the n-6 series. The relative content of saturated fatty acids in microsomes of animals fed orotate was also decreased. 2. Rat liver delta-9 desaturase activity was lower in the group fed orotate. However, delta-6 desaturase activity did not show significant differences between the groups. 3. Microsomal cholesterol content was lower in rats fed orotate than in controls but phospholipid phosphorus contents were similar. These results suggest a direct effect of dietary orotate on the key enzymes which regulates cholesterol liver metabolism. PMID- 1451445 TI - Cytosolic modulators of acyl-CoA: cholesterol acyltransferase (ACAT) activity in hepatic tissue of the chicken (Gallus domesticus). AB - 1. An enzymatic assay for microsomal acyl-CoA: cholesterol acyltransferase (ACAT) activity in chicken hepatic tissues was developed using silicic acid chromatography. 2. ACAT activity was increased in response to liver cytosolic protein preparations suggesting the presence of cytosolic modulators of the enzyme. 3. Fractions containing low molecular weight proteins (12-15 kDa) prepared by molecular sieve chromatography also stimulated ACAT activity. 4. Liver-FABP was specifically implicated as a cytosolic modulator of ACAT activity in chicken liver tissue. PMID- 1451446 TI - Comparison of glycerolipid biosynthesis in homogenates from human, ovine, bovine and rat adipose tissue in vitro. AB - 1. Assay conditions were compared for glycerolipid biosynthesis in homogenates prepared from human abdominal, ovine and bovine subcutaneous, and rat epididymal adipose tissues. 2. In contrast to other species, longer incubation time and greater homogenate concentration resulted in decreased glycerolipid biosynthesis with rat adipose tissue homogenates. 3. Species differences were observed in concentration-dependency for ATP and fatty acids (palmitate, oleate and palmitoleate). 4. Results indicated that glycerolipid biosynthesis transpired at different rates in the four species, and that ovine and human adipose tissue homogenates had similar properties. PMID- 1451447 TI - The Suicide and Aggression Survey: a semistructured instrument for the measurement of suicidality and aggression. AB - Despite the rising concern with the increasing rate of violent and suicidal behaviors in this country and others, we remain relatively limited in our ability to rigorously define, classify, and measure these behaviors. In addition to our previous work in developing self-rating scales assessing aspects of aggressive behaviors, we have developed the Suicide and Aggression Survey (SAS), a new, comprehensive, semistructured interview and research tool, for the purpose of comprehensively evaluating and understanding the multiple constituents of these behaviors, and for assisting in predicting which individuals might be at high risk for suicide or violence. The present report describes the need for such an instrument and the theoretical models that have guided us in constructing it; one of these is a sequential description of the major classes of variables related to aggression and the other is a two-stage model of countervailing forces. Preliminary reliability data and a description of the structure of the interview are included. PMID- 1451448 TI - Prediction of suicide intent in hospitalized parasuicides: reasons for living, hopelessness, and depression. AB - This study examined the risk prediction efficiency of the Reasons for Living Inventory Survival and Coping Beliefs Scale, Beck Hopelessness Scale, Beck Depression Inventory, and the Life Experiences Survey with a sample of 51 newly hospitalized parasuicides. The index of suicidal potential chosen for this study was suicide intent as measured by Beck's Suicide Intent Scale. Regression analyses indicated that the Survival and Coping Beliefs Scale emerged as the single most important predictor of suicide intent. Hopelessness and depression made secondary and nonsignificant contributions. Hopelessness was a significant predictor of suicide intent when analyzed apart from Survival and Coping Beliefs, but not among a subsample of 43 repeat parasuicides. Classification analyses showed that neither hopelessness nor survival and coping beliefs were accurate at classifying low- or high-intent parasuicides. Factors contributing to the efficacy of survival and coping beliefs as a risk prediction index are discussed, as is the false-negative dilemma in suicide risk assessment and prediction. PMID- 1451449 TI - The PBI-BC: a brief current form of the Parental Bonding Instrument for adolescent research. AB - The present report describes the development of a brief form of the Parental Bonding Instrument (PBI-BC) intended to measure perceptions of current parental characteristics. The PBI-BC, consisting of eight items and inquiring into parental characteristics as perceived by the adolescent respondent over the previous 3 months, is shown to closely replicate the factor structure reported for the PBI. The scales are shown to have reasonable internal reliability. Arithmetic difference scores representing the two bipolar factors seem to be adequate for studies requiring easily calculated measures of parental care versus rejection, and parental control versus autonomy. The PBI-BC may be particularly useful in multivariate studies of adolescent samples, where the two dimensions of parental care versus rejection and parental control versus autonomy are thought to be potentially relevant. PMID- 1451450 TI - Construct validation in adolescents of the brief current form of the Parental Bonding Instrument. AB - We have reported elsewhere the development of a brief version of the Parental Bonding Instrument (PBI), which we have called the Parental Bonding Instrument Brief Current form (PBI-BC), for use in survey research in adolescent samples. It was shown in that report that PBI-BC retained the factor structure of the original instrument. The structure remained stable in adolescents' ratings of their mothers and their fathers. Given the evidence of a relationship between the dimensions from the original scale and psychopathology, it was expected that the PBI-BC would be similarly related to measures of psychopathology, namely, that there would be a set of positive correlations between the perceived parental bonding styles of high control and low autonomy-giving and measures of pathology, with a negative relationship between pathology and perceived parental styles of high care and low rejection. In addition, the present study explored the relationships between perceived parental styles and bipolar positive and negative self-concept measures, with the expectations that high control and low autonomy would be associated with more negative self-concept and that high care and low rejection would be associated with more positive self-concept. The results generally confirmed these expectations, suggesting that the brief instrument has adequate construct validity and would be particularly useful as a brief index in studies of adolescents. PMID- 1451451 TI - Suicide attempts of high medical seriousness in schizophrenic patients. AB - A retrospective study was conducted that included all patients who in the previous 6 years had required admission to our hospital for medical reasons following attempted suicide (N = 253). Those diagnosed as schizophrenic (n = 43) in accordance with DSM-III-R criteria were compared with the other nonschizophrenic suicide attempters. Schizophrenic patients were significantly different in that they were younger and generally unmarried, usually used violent methods, made more attempts while in a psychiatric center, and presented a lower incidence of concurrent organic illness than the nonschizophrenics; almost all of them were chronic. A large majority (80%) showed delusional and hallucinatory symptoms at the time of the attempt. In contrast, depressive symptoms were noted in an appreciably lower percentage of subjects than that in other studies of suicidal behavior in schizophrenics. PMID- 1451452 TI - Crisis intervention response and long-term outcome: a pilot study. AB - We investigated whether process variables (therapeutic alliance and insight) measured at the termination of crisis intervention predict long-term treatment compliance and 2-year outcome. Thirty-seven consecutive depressed psychiatric patients assigned to outpatient crisis intervention (CCI) were assessed with both questionnaires and standardized instruments at intake, 1 week, and CCI termination (mean, 6 weeks). Thirty-one subjects (84%) were also evaluated at 1 year and 2-year follow-up. We found that working alliance and development of insight predicted positive global change and symptom improvement at 1 and 2 years' follow-up. Furthermore, the observed correlation between process measures and 2-year outcome was found to be independent of age, sex, symptoms severity at intake, improvement of symptoms at CCI termination, premorbid adjustment, DSM-III R axis I/axis II diagnosis, and therapeutic alliance at intake. PMID- 1451453 TI - DSM-III-R narcissistic personality disorder evaluated by patients' and informants' self-report questionnaires: relationships with other personality disorders and a sense of entitlement as an indicator of narcissism. AB - Modified versions of the revised Personality Diagnostic Questionnaire (PDQ-R) for DSM-III-R personality disorders (PDs) were completed by 60 patients and their informants. Patients' ratings gave a mean number of 4.5 PDs per subject and narcissistic (NAR) PD in 42%. Informants' ratings gave NAR PD in 38%. For patients and informants, NAR PD scores (i.e., the number of positive NAR PD criteria for each subject) were significantly correlated with histrionic (HIS) and borderline (BOR) PD scores and with scores of some PDs outside DSM-III-R's "cluster B." Also, there were significant correlations between patients' and informants' NAR PD scores and between NAR PD scores and total number of positive criteria (i.e., for all 13 PDs) for patients and informants. For patients' ratings, there were significant associations between NAR PD and HIS, BOR, and passive-aggressive (PAG) PDs and, for informants' ratings, between NAR and HIS PDs. There was no significant association between patients' and informants' diagnoses of NAR PD. Grandiosity, the most characteristic feature of narcissism, is related to NAR PD criteria 3 through 6. The patients' evaluation of criterion 6 (i.e., "Has a sense of entitlement ...") shows satisfactory item-total correlation and endorsement frequency, together with "fair to good" reliability when patients' and informants' ratings are compared (kappa = 0.62). The identification of a sense of entitlement by the patient may be a relatively reliable and valid indicator of narcissism. PMID- 1451454 TI - A case of subcortical grey matter heterotopia presenting as bipolar disorder. AB - A case of previously diagnosed bipolar disorder was found to be associated with unilateral subcortical grey matter heterotopia, cortical hemiatrophy, midline shift, and ventriculomegaly on magnetic resonance imaging (MRI). The patient responded to pharmacotherapy with lithium carbonate and carbamazepine. This case dramatically illustrates the need for neuroimaging in psychiatric patients with apparently "functional" affective illness. PMID- 1451455 TI - Psychiatric disorders among wife batterers. AB - Sixty-one male spouse batterers were identified from a population of relatives of treated alcoholics and compared to 319 married or formerly married men without a reported history of battering on lifetime psychiatric diagnoses and antecedent behaviors. Batterers had higher lifetime rates of alcoholism, antisocial personality disorder, and depression than nonbatterers, but not other psychiatric disorders. While batterers and nonbatterers could not be differentiated based on violent behaviors occurring before the age of 15, 95% of batterers reported other fighting as an adult. Batterers also were more likely to have been divorced two or more times and to report repeated infidelity. Implications for treatment of batterers and identifying groups at high risk for battering are discussed. PMID- 1451456 TI - The value of the local lymph node assay in quantitative structure-activity investigations. AB - The development of quantitative correlations between the physicochemical properties of a compound and its ability to act as a skin sensitizer is complicated by the number of variables associated with the current sensitization test data, combined with the absence of a truly objective end point. Recently, however, a novel approach to the assessment of skin sensitization potential, the local lymph node assay (LLNA), has been described, which determines the skin sensitization by measuring lymphocyte proliferation in lymph nodes draining the site of chemical exposure. The assay offers several advantages over traditional methods in the context of quantitative structure-activity relationship studies. In the present work, a range of bromoalkanes has been employed which demonstrate the robustness and reproducibility of the LLNA. Sensitizing activity increased with chain length up to a maximum at C15/C16, whereafter the response declined. The data were modelled against hydrophobicity, expressed as Clog P and (ClogP)2 to fit the biphasic nature of the results. The results demonstrate the utility of LLNA data for interpretation in the context of quantitative structure-activity relationships, the limited number of variables, inter-test reproducibility and quantitative end point, lending themselves to mathematical interpretations. PMID- 1451457 TI - Eyelid dermatitis: an evaluation of 150 patients. AB - This study was performed to evaluate eyelid dermatitis in a group of patients of our Allergy Unit between January 1990 and April 1991. Among the 1158 patients seen during this period, 150 had eyelid dermatitis: 135 females and 15 males, with a mean age of 35 years. Of the 150 patients with eyelid dermatitis, 54 had eczema localized to the eyelids only, 49 to the eyelids and face, 19 to the eyelids and hands, and 28 to the eyelids and other sites. 98 patients (65.3%) were diagnosed as having allergic contact dermatitis, 25 (16.6%) irritant contact dermatitis, 21 (14%) atopic dermatitis, and 6 (4%) seborrhoeic dermatitis. Patch test reactions to nickel sulphate, Kathon CG and fragrance-mix occurred more frequently in patients with eyelid dermatitis than in those without. PMID- 1451458 TI - Irritant cutaneous reactions to N-methyl-2-pyrrolidone (NMP). AB - Several workers in a small electrotechnical company in Norway experienced irritant reactions of the skin after a few days of working with the solvent N methyl-2-pyrrolidone (NMP). Due to concern about the health risk of commonly-used organic solvents, the company had chosen to use NMP when one of its products had to be treated with a solvent. After 2 days of work with NMP, 10 of the 12 involved workers displayed acute irritant contact dermatitis of the hands. According to published reports, NMP is not considered to be particularly irritant to the skin. The Safety Data Sheet of a Norwegian sales firm contained no information on cutaneous hazards, but the Safety Data Sheet of an American producer of NMP stated the risk of severe dermatitis upon prolonged contact. NMP seems to be more irritant to the human skin than reported thus far. PMID- 1451459 TI - Monitoring of skin response to sodium lauryl sulphate: clinical scores versus bioengineering methods. AB - The present trial was designed to evaluate clinical scores (single observer) of sodium lauryl sulphate (SLS)-induced skin irritation in a group of subjects (n = 10) over a 10-day period along with various skin function parameters. In order to avoid significant variations due to secondary phenomena, the following parameters were recorded with non-invasive instruments in this order: skin capacitance (C1; arbitrary units; CM420 Corneometer), transepidermal water loss (TEWL; g/m2.h; Evaporimeter) and laser Doppler flowmetry (CBFV: cutaneous blood flow values; Periflux). All examinations were performed during winter on reclined relaxed subjects present for at least 10 min in a test room with controlled temperature and relative humidity (t degrees: 19.5-20.7 degrees C and RH: 47.3-60.3%). The analysis of differential data (delta = value at tx-value before test; 2-way ANOVA) was made on single parameters as a function of site (volar forearm versus neck) and time (from 24 h after 48-h occlusion with 5% SLS up to 10 days later). The profile of erythema scores over time differed between neck and forearm, but the delta CBFV readings with the laser Doppler instrument did not detect significant site-time interactions. Roughness (blind evaluation with palpating finger) and capacitance readings (delta C1) showed significant differences between sites, but the profile over time was similar in both locations. delta TEWL did not differ according to anatomical location. The reason for different erythema scores on neck and forearm might be related to inherent regional variation of optical properties of the skin or to a substantial contribution of SLS-induced roughness to the readings of erythema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451460 TI - Patch test reactions to metal salts in patients with oral mucosal lesions associated with amalgam restorations. AB - Patch testing with various metal salts was performed in patients with oral mucosal lesions associated with amalgam restorations, by using polypropylene coated aluminium discs. Positive reactions to mercuric chloride were obtained in 5/12 (42%) of these patients, but only in 1/11 patients (9%) with oral mucosal lesions unassociated with amalgam restorations and in 3/36 patients (8%) in a control group without mucosal lesions. The difference between the former group and the control patients is statistically significant (p less than 0.05). In addition, a positive test reaction to copper sulfate was obtained in 2 patients (16%) with amalgam-associated mucosal lesions and negative reactions to mercuric chloride. 2 of the 5 positive test reactions to mercuric chloride, in the patients with lichenoid mucosal lesions associated with amalgam, became lichenoid and persisted for at least 3 weeks. The patients with these reactions were also positive at a concentration of 0.05% mercuric chloride, but were negative to metallic mercury, in contrast to 2 other patients in the same group. This indicates the necessity of including mercuric chloride when patch testing such patients. PMID- 1451461 TI - Occupational dermatitis from exposure to polyurethane chemicals. AB - In addition to asthma, contact dermatitis may also develop from occupational contact with polyurethane (PU) chemicals. 6 cases of allergic contact dermatitis from exposure to PU chemicals were diagnosed in 1974-1990. The present paper summarizes the results and gives detailed descriptions of 3 such patients. 3 patients were allergic to 5 different diisocyanates (DICs), including 4,4' diphenylmethane DIC (MDI), toluene DIC (TDI), 1,6-hexamethylene DIC (HID), and furthermore to diaminodiphenylmethane (MDA). 3 patients were sensitized by exposure to MDI. 2 of these reacted to MDI and MDA, and 1 to TDI in addition. 1 of the 3 patients reacted only to MDA, possibly formed by hydrolysis of MDI. Primary sensitization to MDA and cross-allergy to MDI could explain the reactions of the patients exposed to MDI, but separate sensitization may also be possible. Patch tests with fresh petrolatum (pet.) mixtures were first made and a 2% concentration was recommended for MDI and TDI. In order to determine the stability of DIC test substances, the last 2 patients were tested with old test substances. Tests with MDI 1.5% pet. and TDI 1.5% pet., 5.5 months and 15.5 months old, were positive. The results suggest that, when allergy to PU chemicals is suspected, patch tests should include, in addition to MDA, at least MDI and TDI 1.5-2% pet. They also suggest that test substances can be used for over a year, and that allergy to MDA may point to MDI exposure contained in PU chemicals. PMID- 1451462 TI - A method for identifying causative chemicals of allergic contact dermatitis using a combination of chemical analysis and patch testing in patients and animal groups: application to a case of rubber boot dermatitis. AB - A 63-year-old woman developed allergic contact dermatitis from rubber boots. Initial investigation, by patch testing in the patient and chemical analysis of the causative rubber boots, revealed that mercaptobenzothiazole (MBT) and dibenzothiazyl disulfide (MBTS) were the causative chemicals. Subsequent investigations were performed by patch testing in animal groups. An extract of the causative rubber boots, MBT and MBTS were used for sensitization of guinea pigs by the guinea pig maximization test (GPMT). 3 animal groups, A (with the boot extract), B (with MBT) and C (with MBTS) were successfully prepared. The boot extract was fractionated by column chromatography and thin-layer chromatography (TLC). Each fraction was subjected to patch testing in the animal groups. Positive reactions in all groups would show that the active fractions contained MBT-type compounds, whereas a positive reaction in group A but negative ones in group B and C would show that the active fractions did not contain any MBT-type compounds. Each fraction was then analyzed by gas chromatography (GC), GC-mass spectrometry (GC-MS), direct inlet-MS (DI-MS) and high-performance liquid chromatography (HPLC). By this investigation, we found not only known allergens (MBT, MBTS), but also unknown allergens: S-substituted MBT-type compounds and styrenated phenol (SP). Thus, SP was shown to be a candidate as a human sensitizer even though the patient did not react to it. PMID- 1451463 TI - Evaluation of skin irritancy of sodium lauryl sulphate: a comparative study between the replica method and visual evaluation. AB - For 20 years, using the replica method, we have evaluated the skin irritancy of about 10,000 commercial products which come into contact with the skin. In this method, test substances are usually applied on the flexor side of the upper arm for 24 h by semi-open patch test. Subsequently, skin replicas are taken and skin irritancy is evaluated microscopically. In the semi-open patch test, test substances are not completely occluded as in the closed patch test. Thus, this method is less invasive than the closed patch test method to the tested subjects. In this study, we investigated the sensitivity of microscopic scoring (MS) of the replica and visual scoring (VS) of the skin. Sodium lauryl sulphate (SLS) at 0.02%, 0.05%, and 0.2% was applied on 20 subjects' upper arms, using closed and semi-open methods. In both the closed patch test and the semi-open patch test, the value of MS correlated with the concentration of SLS, while VS did not show such a clear correlation. In addition, we compared 2 clinical tests for skin irritancy which are commonly performed in Japan: VS of 48 h closed patch test reaction on the subjects' upper backs and MS of 24 h semi-open patch test reaction on the subjects' upper arms (replica method). MS on the upper arms resulted in a constant score, regardless of the location of application, while VS on the upper back produced results which differed widely depending on the location. Thus, the replica method is a useful clinical test for skin irritancy, because it is sensitive, reproducible and non-invasive. PMID- 1451464 TI - Results of routine patch testing of 834 patients in Turin. AB - 834 consecutive patients (630 female), aged between 26 and 46 years, who were suspected of having allergic contact dermatitis were patch tested with the GIRDCA standard series during 1989-1990. The most frequent sensitizers observed included nickel sulphate, cobalt, Kathon CG, perfumes, potassium dichromate and balsam of Peru. We have evaluated the influence of individual factors such as sex, age and occupation on the patch test results, and the coexistence of 2 or more unrelated but statistically significant sensitivities. PMID- 1451465 TI - Occupational dermatitis in an accordion repairer. PMID- 1451466 TI - Bullous fixed drug eruption induced by vinburnine. PMID- 1451467 TI - Patch tests with Tactylon in patients with contact allergy to rubber. PMID- 1451468 TI - Occupational contact urticaria from beef associated with hand eczema. PMID- 1451469 TI - Occupational contact dermatitis from cyclohexanone as a PVC adhesive. PMID- 1451470 TI - The patch test dilution of oleamidopropyl dimethylamine. PMID- 1451471 TI - Contact allergy to undecylenamide diethanolamide in a liquid soap. PMID- 1451472 TI - Teats and pacifiers--an allergy risk for infants? PMID- 1451473 TI - Patch test preparations of mercury ammonium chloride under the microscope. PMID- 1451474 TI - Jellyfish dermatitis due to Carybdea marsupialis. PMID- 1451475 TI - Immunologic contact urticaria syndrome from raw rice. PMID- 1451476 TI - Allergic contact dermatitis from dibutyl phthalate, propyl gallate and hydrocortisone in Timodine. PMID- 1451477 TI - Cross-sensitivity between resorcinol, resorcinol monobenzoate and phenyl salicylate. PMID- 1451478 TI - Contact dermatitis from topical alkylamines. PMID- 1451479 TI - Photocontact allergy due to thiocolchicoside. PMID- 1451480 TI - 17 cases of epoxy resin dermatitis in Shanghai. PMID- 1451481 TI - The reaction index: a parameter to assess the quality of patch test preparations. PMID- 1451482 TI - Contact sensitivity to topical aminoglycosides in India. PMID- 1451483 TI - Occupational contact allergy to 1,2-benzisothiazolin-3-one in the manufacture of air fresheners. PMID- 1451484 TI - Sulphanilic acid: divergent results in the guinea pig maximization test and the local lymph node assay. AB - The guinea pig maximization test (GPMT) has proven to be a valuable tool for the identification of the skin sensitization potential of chemicals. The method identifies a hazard which can lead in the EC to compulsory labelling of that chemical. In the present study, data on sulphanilic acid derived from the GPMT has been compared with results from a second guinea pig assay (the cumulative contact enhancement test) and the murine local lymph node assay, both of which require only topical application of chemical. Except for the GPMT, no test identified any sensitizing activity associated with exposure to sulphanilic acid. These latter results are consistent with the experience gained from substantial human exposure in an occupational setting and from which no cases of allergic contact dermatitis to sulphanilic acid have arisen over a 20-year period. In consequence, it is questioned which test protocol in practice has given the more accurate identification of sensitization hazard relevant to man. PMID- 1451485 TI - Prognosis of occupational chromate dermatitis. AB - To elucidate further the natural history and prognosis of occupational chromate dermatitis, 120 affected patients, diagnosed between 1980 and 1989, were reviewed. The incidence of chromate dermatitis in Western Australia appeared to remain unchanged over the decade. 65% of patients were construction workers with cement-induced chromate dermatitis. Workers at greatest risk of sensitization were those mixing bagged cement at the work site. The median age at onset of symptoms was 34 years, with 48% having been exposed to chromate for 5 years or less. Only 37% presented to the dermatologist within 12 months of developing symptoms. 76% of patients had ongoing dermatitis at the time of review. Although 48% of the study population had completely changed their occupation to avoid chromate exposure, symptoms persisted in 69%. A delayed diagnosis of chromate sensitivity was noted to be a predictor of chronicity. In view of the potential chronicity of chromate dermatitis and its associated social and occupational impairment, we recommend the addition of ferrous sulphate while mixing bagged cement at the work site. This simple technique targets the workers at greatest risk of becoming sensitized. PMID- 1451486 TI - Studies on the allergenicity of Baltic amber. AB - Baltic amber is a fossil resin deposited 36-7 million years ago and one source may be the extinct tree Pinites (Pinus) succinifer. Palaeobotanical studies of amber have an extensive literature, but the aspect of allergenicity has not been addressed before. The aim of our study was to present the results from sensitization studies with Baltic amber and to discuss these in view of possible cross-reactivity with contact allergens in colophony. It is concluded that allergens found in colophony can also be present in Baltic amber. The main resin acids were identified in an ether-soluble extract of amber. Amber suspended in petrolatum caused positive patch test reactions in patients with contact allergy to colophony. Furthermore, animals sensitized to colophony showed positive reactions to amber, but animals induced with amber did not react when challenged with amber. A use test with an amber necklace in patients with positive test reactions to amber and colophony was negative, which supports the view that amber in personal ornaments is not a clinical problem. PMID- 1451487 TI - Erythema multiforme reaction to patch testing. AB - A young woman developed erythema multiforme in association with multiple patch test reactions. Sequential patch testing revealed 2 true positive reactions (colophony and fragrance mix), and was not associated with flare of erythema multiforme-type lesions. The development of erythema multiforme should be included in the list of possible adverse reactions to patch testing, albeit a rare occurrence. PMID- 1451488 TI - A survey of formaldehyde in shampoos and skin creams on the Danish market. AB - To evaluate the exposure of the general population to formaldehyde from the use of cosmetic products, as well as to monitor whether cosmetic products comply with national regulations, 285 shampoos, creams, etc., were analysed for formaldehyde. Identification and determination of formaldehyde was performed by the EEC method for the analysis of formaldehyde in cosmetic products. It was shown that 29.5% of the products investigated contained 0.001%-0.147% total formaldehyde. In 10 of the products (3.5%), total formaldehyde content was > 0.05%. 8 of these products contained > 0.05% free formaldehyde. None of these products was labelled 'contains formaldehyde'. 17 of the products investigated were declared to contain specific formaldehyde-releasers. Formaldehyde could not be detected (detection limit 0.001%) in cosmetic products that were declared to contain Bronidox/Bronopol. PMID- 1451489 TI - Skin reactivity to metallic cobalt in patients with a positive patch test to cobalt chloride. AB - 458 consecutive patients were patch tested with a metallic cobalt disc as a supplement to the standard series. 23 patients had a positive reaction to CoCl2 1% pet. Of these, 19 were tested with the cobalt disc. 11 had a positive reaction and 5 a questionable reaction. There were no positive reactions to the cobalt disc in patients with a negative patch test to CoCl2 1% pet. Patch testing with CoCl2 1% pet. diagnoses all patients with allergy to metallic cobalt, but the test method is limited by a high number of irritant and questionable reactions. PMID- 1451490 TI - Heat treatment of Japanese lacquerware renders it hypoallergenic. AB - Japanese lacquer is made from the sap of the Japanese lacquer tree (Toxicodendron vernicifluum), a member of the Anacardiacae plant family. Objects painted with this material are described collectively as lacquerware. Both fresh lacquer and lacquerware may evoke allergic contact reactions ascribable to the urushiols contained therein. In this study, we have examined the effects of heating on the ability of lacquerware to elicit an allergic contact reaction. Lacquer films prepared with and without heat treatment were tested on urushiol-sensitive subjects. Patch test reactions were strongest to untreated film and decreased with increasing level of heat treatment. Assays for free urushiol in the lacquer films demonstrated that free urushiol content decreased with increasing heat treatment and that urushiols with saturated and monounsaturated alk(en)yl chains predominated. PMID- 1451491 TI - Diagnostic value of the lymphocyte proliferation test in nickel contact allergy and provocation in occupational coin dermatitis. AB - The lymphocyte proliferation test (LPT) was compared with the patch test in the diagnosis of nickel contact sensitivity. Of the 21 subjects with nickel contact allergy, the patch test detected 20 (95%). The subject remaining negative in the patch test was positive in the intradermal test. 18/21 subjects with nickel contact sensitivity were positive in the LPT, whereas in the control group 2/23 subjects were false positive. These results were obtained at nickel sulfate concentrations of less than 10 micrograms/ml, higher concentrations led to nonspecific lymphocyte stimulation. 3 nickel-sensitive cashiers with suspected coin contact-induced deterioration of their hand eczema were challenged by having them count nickel-containing coins daily for 15 min. 2 of them developed vesicular eczema on their palms and fingers in 2 to 3 days. The present results show that the LPT is a reliable additional test in the diagnosis of nickel contact sensitivity. Furthermore, provocation is a valuable procedure when assessing the relevance of nickel contact in occupational hand eczema in certain occupations. PMID- 1451492 TI - Contact sensitivity to N-A Dressing. PMID- 1451493 TI - Occupational contact dermatitis from airborne nicergoline. PMID- 1451494 TI - Compositae dermatitis presenting as hand eczema. PMID- 1451495 TI - Generalized eczema from vitallium osteosynthesis material. PMID- 1451496 TI - Systemic contact dermatitis from an orthodontic appliance. PMID- 1451497 TI - Allergic contact dermatitis from diaminodiphenylmethane in an ostomy bag. PMID- 1451498 TI - Contact allergy to piroxicam gel. PMID- 1451499 TI - Concomitant sensitization to enoxolone and mafenide in a topical medicament. PMID- 1451500 TI - Contact cheilitis in Singapore. PMID- 1451501 TI - Immediate and delayed hypersensitivity to the nettle plant. PMID- 1451502 TI - Caustic ulcers caused by calcium hydroxide in 2 adolescent football players. PMID- 1451503 TI - Allergic contact dermatitis from fepradinol. PMID- 1451504 TI - Allergic contact cheilitis from a lipstick containing oxybenzone. PMID- 1451505 TI - Laxative-induced contact dermatitis. PMID- 1451506 TI - Normal standards for dermatological health screening at places of work. PMID- 1451507 TI - Delayed hypersensitivity to cefuroxime. PMID- 1451508 TI - Allergic contact dermatitis due to 1,2-benzisothiazolin-3-one in paint manufacture. PMID- 1451509 TI - Can 'label dermatitis' become 'creeping neurotic excoriations'? PMID- 1451510 TI - Vulvar contact dermatitis from nifuratel. PMID- 1451511 TI - Contact dermatitis from ketoconazole cream. PMID- 1451512 TI - Allergic contact dermatitis from ethanol in a transdermal estradiol patch. PMID- 1451513 TI - Occupational allergic contact dermatitis from ethyl chloro oximido acetate. PMID- 1451514 TI - Contact sensitization by alternative topical medicaments containing plant extracts. The Dutch Contact Dermatoses Group. PMID- 1451515 TI - Systemic contact dermatitis from tea tree oil. PMID- 1451516 TI - Clinical trial on termination of early pregnancy with RU486 in combination with prostaglandin. AB - Termination of early pregnancy was performed in 1572 healthy women with RU486 (mifepristone, 600mg orally once), followed 36-60 hours later by administration of methyl ester of dl-15-methyl-PGF2 alpha (PG05, 1mg vaginal suppository). Complete abortion was accomplished in 91.2% (1433/1571), incomplete abortion in 4.8% (76/1571), and continued pregnancy in 3.9% (62/1571). The time elapsed between RU486 intake and complete expulsion was 2.4 +/- 1.3 days. Expulsion took place on the third day in 935 women (72%), and on the 4th day in 273 women (21.0%). Uterine bleeding occurred on the second or third day after RU486 intake in 1256 women (88.8%), and lasted 11.7 +/- 6.4 (SD) days, range 2-55 days. One subject had blood transfusion due to excessive bleeding. The main side effects were nausea/vomiting (22.3%), abdominal pain (10.2%), headache/dizziness (4.1%) and diarrhea (2.8%). Fatal side effects have not been reported in this study. About 73% of subjects with complete abortion assessed the treatment as good to excellent. Even in the failed cases, 25-42% of subjects considered the treatment as good. Further studies are needed to determine the optimal dose of the RU486 regimen. It should be emphasized that the treatment must be used under close medical supervision in order to monitor the uterine bleeding. PMID- 1451517 TI - Role of ultrasonography in managing IUD-related complaints. AB - The study included 211 women using Cu-T 380A, of whom 155 presented with complaints related to IUD use. All women were examined by real-time ultrasound using abdominal sector and/or vaginal scanners. The parameters that were studied included the top-fundal distance (distance between the device top and the highest point in the uterine cavity), the intercornual and the fundus-isthmus diameters (of the uterine cavity). Any abnormal finding was also recorded. About 50% of complainers had top-fundal distance more than 4 mm, compared to 28% of non complainers. An intercornual diameter, too small (less than 30 mm) or too wide (greater than or equal to 38 mm), was significantly more frequent in women complaining of bleeding and pain. Other abnormal findings were diagnosed in 25% of complainers compared to 7% in those without complaint. These findings included partial expulsion, appearance suggestive of pelvic inflammatory disease, ovarian swellings, embedding and fibroid uterus. Ultrasonography can give useful insights in managing IUD-related complaints in selected cases. PMID- 1451518 TI - Comparison of two uterine cavity-shaped IUDs. AB - For the purpose of lowering the pregnancy rate of the uterine cavity-shaped stainless steel IUD (first generation UCD) and maintaining its advantages, the copper-plated uterine cavity-shaped IUD (second generation UCD or UCDcu) was designed. A randomized use-effectiveness study in ten centres with the UCDcu and UCD have been analyzed at twelve months. The UCDcu had a significantly lower pregnancy rate (0.3 per 100 women) than the UCD (2.9 per 100 women), p less than 0.005. Whereas, the other cumulative rates such as expulsion, removals for bleeding and pain, and other personal were not significantly different for the two IUDs, p greater than 0.05. PMID- 1451519 TI - Lipid and biochemical changes after low-dose oral contraception. AB - A randomized double-blind study of the metabolic effects of 2 low-dose combined oral contraceptives was carried out in Singaporean women. The subjects comprised 58 women randomly allocated to two treatment groups (29 each): norethisterone 1 mg/ethinyl estradiol 35 micrograms (NET/EE) or levonorgestrel 150 micrograms/ethinyl estradiol 30 micrograms (LNG/EE) and a control group of 23 women using intra-uterine devices (IUD). Blood samples were taken on admission and at 3 and 12 months after pills or insertion of IUDs. Fasting glucose levels were decreased while 2h glucose and triglyceride were increased throughout the treatment period in NET/EE group [corrected]. LNG/EE group only showed significant increase of 2h glucose at 12 months and decrease of LDL cholesterol at 3 months while total cholesterol was significantly suppressed at 3 and 12 months [corrected]. The atherogenic index, LDL/HDL cholesterol was significantly reduced by 12 months. Both groups had no change in hemoglobin, hematocrit and total protein levels but alkaline phosphatase, bilirubin and aspartate transaminase (SGOT) were suppressed. While NET/EE suppressed albumin significantly, this was not observed with LNG/EE group. However, these differences observed with use of each pill preparations, were not so obvious between treatment groups and control. Changes in total, HDL and LDL cholesterol and SGOT were not significantly different than the IUD group. Furthermore, except for 2h glucose, there was no increase in the number of abnormal parameters after treatment. On the contrary, there was a reduction of abnormal values in most liver function parameters. Thus, except for glucose intolerance, the observed changes in metabolic parameters may not constitute any clinical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451520 TI - Long-term effect of low-dose combined steroid contraceptives on body iron status. AB - The present study was aimed to evaluate iron metabolism in active and healthy adult women having taken oral contraceptives (OC) long-term. Mean dietary iron intake in age-matched control and experimental groups was adequate. Serum ferritin used as a marker for body iron stores was marginal in both groups underlying a high prevalence of deficient-iron reserves among subjects. This parameter was not correlated to the iron content of the diet. The serum iron concentration was significantly higher in OC users than control subjects (p less than 0.001). Biochemical results commanded a discussion on the pertinence of evaluating the total dietary iron intake and on the sensitivity of biochemical methods used to assess the iron status. PMID- 1451521 TI - Oral contraceptives in premenstrual syndrome: a randomized comparison of triphasic and monophasic preparations. AB - Thirty-seven women with cyclical mood changes, either only in the premenstrual phase ('pure PMS') or during the entire cycle with premenstrual aggravation ('PMA'), were recruited to participate in a randomized study investigating the effect of three different oral contraceptives (OCs) on mood symptoms; 32 out of the 37 women completed the study. The monophasic ethinylestradiol (EE)/desogestrel (DSG) OC was compared, in a single (doctor)-blind cross-over design, with a monophasic and a triphasic levonorgestrel (LNG)-containing combined OC. The women kept a record of their symptoms and complaints by noting daily ratings using a validated visual analogue scale. One pretreatment cycle was followed by four treatment cycles, two cycles on each OC. All OCs had a beneficial effect on the PMS symptoms compared to the pre-treatment period. There were no changes between consecutive cycles. Cyclical symptom changes were noted during all OC treatment. The monophasic desogestrel pill provoked less changes in mood parameters than the monophasic and triphasic levonorgestrel OCs. However, physical complaints were less frequently reported during the use of the triphasic preparation as compared to the monophasic desogestrel preparation. Women with 'pure' PMS (premenstrual syndrome) were more consistent in their reactions on OCs compared to women with PMA. PMID- 1451522 TI - Ovarian activity and bleeding patterns during extended continuous use of a combined contraceptive vaginal ring. AB - A combined contraceptive vaginal ring with a mean release rate of 0.015 mg of ethinyloestradiol and 0.120 mg of 3-ketodesogestrel per day was used by female volunteers, for either 28, 42, 56 or 84 days. Contraceptive efficacy was assessed by pelvic ultrasound scanning, endocrine monitoring and cervical mucus assessment. Menstrual diary cards were analysed to assess the effect on cycle control. Ovulation inhibition was seen in all treatment groups. Following removal of the ring, a return to an ovulatory cycle was observed in all volunteers. With extension of the treatment cycle beyond the recommended 21 days, there is an increase in the occurrence of bleeding and spotting episodes. This can be compared to patterns obtained during continuous use of combined oral contraceptives. PMID- 1451523 TI - Study to determine the correlation between condom breakage in human use and laboratory test results. AB - The present study examined the value of laboratory tests in predicting condom breakage for 20 lots of latex condoms which differed in age, storage history and laboratory test performance. Two-hundred-sixty-two participating U.S. couples used a total of 4589 latex condoms (mean = 229 condoms per lot, range 224-235). Breakage rates ranged from 3.5 percent for a brand new condom lot to 18.6 percent for a lot that was 81 months old at the time of the study. The statistical predictor models, separately using ultimate elongation from the tensile test, the Condom Quality Index from the airburst volume test, and the percent of condoms failing the airburst volume test as the independent variables and the condom breakage rate as the dependent variable, all appear to have a high level of accuracy in predicting condom breakage in use. The three models had correlation coefficients (R2s) of 0.81, 0.74 and 0.69, respectively. Perhaps the most unexpected result was that the age of the condom lot was the best predictor of condom breakage during use (correlation coefficient (R2) = 0.92). Although the present investigation does not provide sufficient justification to use age as the only factor for decisions on condom lot disposition, it does provide some guidance. PMID- 1451524 TI - Post-coital contraceptive agents from extracts of Sri Lankan alcyonacean soft corals--I. AB - Dichloromethane-methanol (1:1) extracts of ten species of alcyonacean soft corals were screened for post-coital interceptive effects on female rats, using oral administration, from day 1 to day 7 of pregnancy. Significant suppression of fertility was observed in the animals treated with the crude extracts of Sarcophyton ehrenbergi (250 mg/kg/day, P less than 0.05; 500 mg/kg/day, P less than 0.001), Sinularia crispa (500 mg/kg/day, P less than 0.05; 1000 mg/kg/day, P less than 0.001), Sinularia abrupta (1000 mg/kg/day, P less than 0.001), Sinularia spp--III (500 mg/kg/day, P less than 0.05). This antifertility effect appears to be due to interruption of embryonic events during implantation and/or pre-implantation periods. PMID- 1451525 TI - Immunohistochemical localization of basic fibroblast growth factor in mature and developing retinas of normal and RCS rats. AB - Basic fibroblast growth factor (bFGF) delays photoreceptor degeneration when injected intraocularly in Royal College of Surgeons (RCS) rats with inherited retinal dystrophy. In the present study, we have determined the localization of endogenous bFGF in retinas of normal and RCS rats during the normal developmental period (postnatal days 0-20) and the period of photoreceptor degeneration in RCS rats (days 20-90). bFGF was localized immunohistochemically by indirect immunoperoxidase using two different polyclonal antibodies and one monoclonal antibody against bFGF. bFGF was present in retinas as early as birth, and remained through adult age. Controls using either PBS, non-immune IgG or antibody preabsorbed with bFGF peptide were devoid of label. In normal rats between the ages of birth and postnatal day (P) 4, bFGF was found in developing ganglion cells, superficial blood vessels, some of the innermost cells in the neuroblastic layer, developing horizontal cells, and retinal pigment epithelial (RPE) cells. Between P0 and P4, the intensity of staining increased significantly in horizontal cells. From P6-P10, some cells in the inner nuclear layer remained positive, but horizontal cell staining became less intense in the central retina. The superficial vessels, ganglion cells and RPE cells also remained positive for bFGF. At P20-25, when the retina was essentially mature, bFGF was found in RPE cells, most cells of the ganglion cell layer, and many cells of the inner nuclear layer, but horizontal cells and blood vessels showed a lower concentration of bFGF than they did at younger ages. At P45 and older, blood vessels no longer showed bFGF immunoreactivity. The staining pattern in RCS rats was indistinguishable from that for normal rats at all ages examined. These results show that bFGF is present in the developing and adult rat retina in some neural cells, in addition to vessels and RPE cells. The transient elevated expression of bFGF immunoreactivity in developing horizontal cells and blood vessels suggests a possible role for this growth factor in retinal development. In addition, if RCS retinas possess any difference in bFGF localization or concentration compared to normal retinas, it must be too small to detect by immunohistochemical means, or at least with the reagents used. PMID- 1451526 TI - Oxygen-induced retinopathy in the rat: hemorrhages and dysplasias may lead to retinal detachment. AB - Rearing neonatal rats in hyperoxia induces the development of retinal hemorrhages and retinal dysplasia. Albino rats were placed in 80% oxygen immediately after birth and were exposed for either 5, 10, or 14 days, followed by sacrifice or exposure to normoxia for an additional 2, 4, 5, 7, 8, 10, 38, 45 or 56 days. Control rats were simultaneously raised in room air and sacrificed at the same times. All animals were enucleated and their eyes processed for light and electron microscopy. Eyecups were trimmed to facilitate cross-sectioning of the retina in the vertical meridian. No control rats showed signs of retinal hemorrhages or of dysplastic folds or rosettes. Nor did the retinas of rats killed immediately after oxygen exposure contain hemorrhages, but the incidence of retinal folds or rosettes in this group was 54%. For rats exposed to combinations of hyperoxia and brief normoxia (10 days or less), 40% suffered hemorrhages and 50% developed retinal folds or rosettes. Although hemorrhages were more prominent in rats subjected to longer periods of oxygen (73% of all rats exposed for 14 days followed by brief normoxia vs. 6% of those exposed for 5 days followed by brief normoxia), the incidence decreased with time post-exposure in room air. Hemorrhages occurred in 100% of the rats raised in oxygen for 14 days followed by 2 days in room air, and decreased to 50% by 7 days in room air and to 0% by 38 days, indicating a spontaneous resolution with time. In each case, the blood appeared to leak from the newly-forming vessels of the deep capillary net, with most of the red blood cells migrating to the subretinal space. Retinal fold or rosette formation, indicative of developmental dysplasia, occurred in a fraction of virtually all groups of exposed rats, and persisted at the longest post-exposure periods. These two manifestations of oxygen-induced retinopathy are emphasized because they lead to an abnormal separation of the retina from the epithelial layer, which may increase the likelihood of the most serious consequence of ROP--retinal detachment. In fact, all rats that endured post-exposure periods of 38 days or longer before sacrifice exhibited retinal detachment. PMID- 1451527 TI - Ultrastructural localization of hydrogen peroxide in experimental autoimmune uveitis. AB - One of the most prominent features of S-antigen induced uveitis is the massive infiltration of polymorphonuclear leukocytes (PMNs) and mononuclear cells in the ocular tissues and fluids. These inflammatory cells generate reactive oxygen metabolites as microbicidal agents and release these oxidants into the surrounding tissues. Using the cerium perhydroxide method, we have localized subcellular hydrogen peroxide in various inflamed ocular tissues. Most notably, the positive electron-dense granules were seen in the plasma membranes of PMNs that were infiltrating in the retina and uvea. These deposits were noted also in PMNs located within the extravascular spaces. For the intravascular PMNs, the positive reaction products were seen in much lower concentrations. A direct demonstration of substantial concentrations of hydrogen peroxide in experimental autoimmune uveitis, therefore, suggests the possibility that this reactive metabolite is an inflammatory mediator in this condition. PMID- 1451528 TI - Suitability of slit lamp retroillumination photographs for classifying cataracts according to 'Lens Opacities Classification System II (LOCS II)'. AB - The Lens Opacities Classification System II (LOCS II) utilizes photographic standards (two retroilluminated Neitz-CTR and one standard slit lamp Zeiss photographs) for the classification of cortical and posterior subcapsular cataracts, nuclear color and nuclear opalescence. However, dedicated photographic devices, particularly retroillumination cameras, are not always available and this study was aimed at evaluating the suitability of a retroillumination photographic technique with a standard slit lamp camera for cortical and posterior subcapsular cataract classification according to LOCS II. Two observers examined 273 eyes. Kappa statistics demonstrated that agreement between the standard slit lamp, clinical grading (according to published LOCS II methodology) and photographic grading (according to our photographic technique), as well as inter- and intraobserver reproducibility, were excellent (Kappa > 0.74) for the classification of all lenticular regions. The results indicate that a standard slit lamp camera can be as useful as a dedicated retroillumination camera when LOCS II standards are used for cataract classification. PMID- 1451529 TI - Concentration and molecular weight dependency of rabbit corneal epithelial wound healing on hyaluronan. AB - Hyaluronan (hyaluronic acid) is a high molecular weight viscoelastic polymer which has been postulated to enhance wound healing. We investigated the dose and molecular weight (9 x 10(4)-280 x 10(4) dependent effects of hyaluronan on the rate of migration of rabbit corneal epithelium in organ culture and on wound closure in vivo after debridement with n-heptanol. When corneal blocks were cultured with hyaluronan for 20 hours, distances of epithelial migration significantly increased over exposed stroma in proportion to hyaluronan concentration. However, there was no difference in the stimulatory action of hyaluronan on epithelial migration when corneal blocks were cultured at 1 mg/ml of hyaluronan irrespective of changes in the molecular weight range between 9 x 10(4) and 280 x 10(4). Glycosaminoglycans other than hyaluronan (chondroitin, chondroitin sulfate, keratan sulfate and heparan sulfate) failed to increase the epithelial migration. When hyaluronan eye drops were instilled after corneal epithelial removal with n-heptanol, hyaluronan stimulated wound closure in a dose dependent manner, but its stimulatory efficacy was not dependent on molecular weight. PMID- 1451530 TI - Monitoring the genotoxicity of radiocontaminants in Swedish lakes by fish micronuclei. AB - The frequency of micronuclei in erythrocyte cells from fish collected in six Swedish lakes with high concentrations of radiocaesium and other suspected natural and induced pollutants, was investigated. The frequency was enhanced in some lakes but was not correlated with caesium concentrations. Fish could prove to be interesting models for investigations of ionizing radiation effects at low doses because of their sensitivity. PMID- 1451531 TI - Silver staining of synaptonemal complexes in surface-spread spermatocytes of fallow deer (Dama dama L.). AB - Surface-spread spermatocytes of the fallow deer were examined by light microscopy after silver staining. The development and behaviour of synaptonemal complexes and the partial synapsis of the X and Y chromosomes were investigated during leptotene to diplotene chromosome pairing. PMID- 1451532 TI - An ultrastructural evaluation of the reaction of the host cell membrane to the invasive phase of Candida albicans. AB - Ultrastructural studies of the invasive form of Candida albicans in patients with acute or chronic candidosis have demonstrated either (a) a close seal between the host cell membrane and the fungal cell wall or (b) a ruptured or damaged host cell membrane at the point of invasion. This was observed in samples from either oral or vaginal candidosis as the pathogen successfully enters the adjoining host cell. The variations appear to be related to the degree of resistance of the host cell membrane to the invading pathogen. This view is discussed. PMID- 1451533 TI - Cytotoxic effects of antimony trichloride on mice in vivo. AB - Clastogenic effects of antimony trichloride, used in small industries, were monitored in laboratory bred white Swiss mice in vivo, following oral administration by gavaging, after 6, 12, 18 and 24 h. Chromosomal aberrations were principally breaks and damaged cells observed from bone marrow preparations. The frequencies of chromosomal aberrations were directly related to the dose used and were significantly higher than the control. The chemical did not alter the frequency of dividing cells to any significant level. PMID- 1451534 TI - Role of interleukin 2, interleukin 4 and interleukin 5 in the T helper cell driven B cell polyclonal differentiation in the elderly. AB - There is evidence for an impaired T cell-mediated B cell response during senescence. In thirty aged donors, pokeweed mitogen (PWM)-driven immunoglobulin (Ig) synthesis by B cells co-cultured with autologous enriched CD4+ lymphocytes and low amounts of monocytes, was evaluated. Under such experimental conditions, elderly cultures displayed a reduced IgG and/or IgM production when compared with the younger counterpart. Moreover, interleukin (IL)-2 and/or IL-5 addition to cultures led to an enhancement of Ig release. In contrast, IL-4 supplementation failed to positively modulate B cell differentiation. At the same time, aged cells cultured in the presence of IL-2 + IL-5 exhibited an increased Ig synthesis, while the addition of IL-2 + IL-4 or IL-4 + IL-5 mixtures did not induce any significant effect in comparison with homologous untreated samples. The results suggest a critical role for IL-2, IL-4 and IL-5 in the modulation of T helper cell-driven B cell polyclonal responsiveness in the elderly. PMID- 1451535 TI - A method for G-banding chromosomes in one-cell mouse embryos. PMID- 1451536 TI - Nuclear proteins of hamster hepatoma after administration of antitumour agents. AB - One- and two-dimensional gel electrophoretic analysis of nuclear proteins of Kirkman-Robbins hepatoma was used to study the effects of the tumour growth inhibitors methotrexate (MTX) and acyclonucleoside (DHPQtB) on protein composition. MTX and DHPQtB inhibited Kirkman-Robbins hepatoma growth by 89.2 +/- 3.5% and 16.3 +/- 6.1% respectively. The biosynthesis and/or metabolism of some polypeptide spots was affected by these antitumour agents, especially among components with molecular wt/isoelectric points of 52,000-64,000/4.9-5.5, 69,000 78,000/5.0-5.9 and 88,000-100,000/5.1-5.9. PMID- 1451537 TI - Deep vein thrombosis in spinal cord injury. Summary and recommendations. PMID- 1451538 TI - Deep venous thrombosis in spinal cord injury. Overview of the problem. PMID- 1451539 TI - Pathogenesis of venous thrombosis. AB - This brief review attempts to describe the present understanding of the pathogenesis of venous thrombosis in general with special reference to venous thromboembolism in spinal cord injury patients with paralysis. The component parts of Virchow's triad are examined. Most venous thrombi seem to originate in regions of slow blood flow, ie, the large venous sinuses of the calf and thigh or in valve cusp pockets. Decreased blood flow or even stasis due to lack of the pumping action of the large muscle packages in paralyzed patients is undoubtedly one of the major factors. As blood pools, activation products of the coagulation system accumulate locally leading potentially to local hypercoagulability. Activation products of clotting and fibrinolysis can induce endothelial damage which in turn leads to further activation of the hemostasis system. Endothelial damage may also result from distension of the vessel walls by the pooling blood. Blood flow is further decreased by hyperviscosity due to elevated fibrinogen levels and dehydration. Some spinal cord injury patients may sustain direct trauma to the legs; others may encounter vessel wall damage by the immobilized limbs. Shortly after injury, certain changes develop in the clotting system, especially increases in components of the von Willebrand factor macromolecular complex and increased platelet aggregability which could further contribute to hypercoagulability. Recently, an inhibition of the fibrinolytic system was suggested which also could add to a prothrombotic state. All of these interrelated processes clearly explain the high risk of venous thromboembolism in spinal cord injury patients with paralysis which has been clearly demonstrated by many investigators. It is hoped that intense thrombosis prophylaxis will reduce the incidence of this potentially devastating complication. PMID- 1451540 TI - Deep vein thrombosis in spinal cord-injured patients. Evaluation and assessment. PMID- 1451541 TI - Management of deep vein thrombosis in spinal cord injury. PMID- 1451542 TI - Venous thromboembolism in spinal cord injury patients. PMID- 1451543 TI - China's expanded program on immunization. PMID- 1451544 TI - Isradipine treatment for hypertension in general practice in Hong Kong. AB - A 6-week open study of the introduction of isradipine treatment was conducted in general practice in Hong Kong. 303 Chinese patients with mild to moderate hypertension entered the study. Side effects were reported in 21% of patients and caused withdrawal from the study in 3 patients. The main side-effects were headache, dizziness, palpitation and flushing and these were not more frequent than reported in other studies with isradipine or with placebo. Supine blood pressure was reduced (P less than 0.01) from 170 +/- 20/102 +/- 6 mmHg to 153 +/- 19/92 +/- 8, 147 +/- 18/88 +/- 7 and 144 +/- 14/87 +/- 6 mmHg at 2, 4 and 6 weeks respectively in evaluable patients. Similar reductions occurred in standing blood pressure and there was no evidence of postural hypotension. Normalization and responder rates at 6 weeks were 86% and 69% respectively. Dosage was increased from 2.5 mg b.d. to 5 mg b.d. at 4 weeks in patients with diastolic blood pressure greater than 90 mmHg and their further response was greater than those remaining on 2.5 mg b.d. PMID- 1451545 TI - Protective effect of puerarin against myocardial reperfusion injury. Myocardial metabolism and ultrastructure. AB - To ascertain the beneficial effect of puerarin on the myocardium against reperfusion injury, studies on myocardial metabolism and ultrastructure were made. Twelve dogs divided into two equal groups were placed on moderate hypothermic cardiopulmonary bypass, and their hearts were subjected to 140 minutes cold cardioplegic arrest and 60 minute reperfusion. In the control group, the hearts were perfused with crystalloid cardioplegic solution (CPS) every 20 minutes during arrest. In the treated group, the hearts received CPS containing puerarin (2 mg/kg). Myocardial oxygen consumption, lactate production, creatine phosphokinase (CPK) release, water content and ultrastructural alterations were determined before ischemia, during cardiac arrest and at reperfusion. The results showed that intermittent infusion of CPS containing puerarin significantly decreased myocardial lactate production during ischemia, as well as myocardial oxygen consumption, CPK release and water content during reperfusion. Under electronmicroscopy, the degree of ischemic damage judged by a scoring method was less pronounced in the puerarin group than in the control. The authors conclude that puerarin has protective effects on the function of hearts that have undergone long periods of arrest and reperfusion. PMID- 1451546 TI - Electrophysiologic follow-up in dogs receiving intracoronary ethyl alcohol injection. AB - 96% ethyl alcohol was injected into a diagonal branch of the left anterior descending coronary artery of 10 out of 12 anesthetized dogs, and saline solution was injected in the remaining 2. After chest closure, the dogs were subjected to ambulatory monitoring (H) during days 1, 2, 3 and 7. The electrophysiologic study (EPS) and signal-averaged electrocardiography. (SA-ECG) were performed before the injection and again at day 7 after injection. H failed in one dog which died of ventricular fibrillation. In the other 9 dogs that received alcohol injection, H showed frequent ventricular premature and ventricular tachycardia (VT) after injection; six of the 9 dogs sustained VT, which was not inducible by EPS. VT was not found in 2 control dogs receiving saline solution injection. The SA-ECG showed no ventricular late potentials in dogs receiving alcohol injection. Post ablation ventricular arrhythmia (including VT) occurred after intracoronary ethyl alcohol injection in all dogs. Arrhythmogenicity markedly declined during the first 3 days and almost completely disappeared on day 7 after ablation. There was no evidence in favor of reentry as the mechanism of these arrhythmias. Enhanced automaticity was considered as the mechanism for ventricular arrhythmia. PMID- 1451547 TI - Potential pitfalls in using DNA probes to counsel Duchenne and Becker muscular dystrophy families. AB - Although the accuracy in prenatal diagnosis and carrier detection with DNA probes in families with Duchenne and Becker's muscular dystrophies is very high, various factors limit the accuracy of these probes in many families. We report four potential pitfalls, ie, intragenic recombination, genetic heterogeneity, germline mosaicism, and an evolving genetic defect encountered in a population of Duchenne and Becker families, and describe a strategy to incorporate these factors into genetic counseling. PMID- 1451548 TI - Treatment of blepharospasm, hemifacial spasm and strabismus with botulinum a toxin. AB - Thirty patients with blepharospasm, hemifacial spasm, strabismus and entropion were treated with botulinum A toxin giving satisfactory results. Rapid spasm relief, correction of strabismus and entropion were obtained. Only mild, transient and local side-effects occurred. The patients were followed up for 4-12 weeks with no recurrence. The clinical results show that local injection of a minute dose of botulinum A toxin in treating blepharospasm, hemifacial spasm, strabismus and entropion is a safe, effective and simple method of nonsurgical therapy. PMID- 1451549 TI - Linkage between Rh blood group and autosomal dominant retinitis pigmentosa in ten Chinese families. AB - Since Fei et al reported a tentative linkage between ADRP and the Rhesus(Rh) blood group in the unrelated Chinese families in 1987, additional individuals of these ADRP families have been typed for Rh. Further linkage analysis with the LIPED Program on the Rh data of the ten ADRP families showed a maximum summed LOD score of 2.01 at theta = 0.12, which is a further suggestion of linkage between ADRP and Rh. However, genetic heterogeneity certainly exists in these families. It is our presumption that ADRP in those families, which do not exhibit linkage to 3q markers, may map to the short arm of chromosome 1. PMID- 1451550 TI - CT evaluation of malformed external and middle ear and its surgical correlation. AB - This study evaluated the diagnostic value of high resolution CT (HRCT) for atresia of the external auditory meatus (EAM) and isolated middle ear malformation. CT scan of the temporal bone was done in 33 patients with such disorders and 5 patients with otosclerosis etc. were studied in the same way for comparison. Coronal HRCT clearly showed conditions of the atresia plate and malformation of the malleus, incus, abnormal course of facial canal and changes in the vestibular window. The axial HRCT is useful to demonstrate the articulations in between the malleus, incus, stapes and the cochlear window. All the HRCT findings were confirmed during operation. Axial and coronal HRCT for external and middle ear deformation is highly valuable for decision making and surgical planning. PMID- 1451551 TI - Location of lectin UEA-I receptors in histological diagnosis of nasopharyngeal precancerous lesion. AB - Three kinds of lectins (UEA-I, ConA, PNA) were used to study normal, dysplastic, neoplastic nasopharyngeal epithelium by lectin affinitive histochemical method. UEA-I (ulex europeus agglutinin-I) displayed membrane distribution in normal squamous epithelium, but most of nasopharyngeal carcinoma cells were negative. Notably, severe dysplastic epithelium (precancerous lesion) exhibited a strong membranous and cytoplasmic affinity, which contrasted sharply with the normal epithelium and carcinoma cells. The statistically significant difference in the content and distribution of lectin UEA-I in these three groups suggest that UEA-I is a hopeful marker for diagnosing precancerous lesion of the nasopharynx. However, PNA and ConA are of less diagnostic value. PMID- 1451553 TI - Glial polyp of the cervix. A case report. PMID- 1451552 TI - Comparison of serum bactericidal activity of 4 fluoroquinolones in healthy volunteers. AB - In vitro antibacterial activities (MBCs) and serum bactericidal activities (SBAs) of fluoroquinolones were compared. The MBCs were measured by the agar disk dilution test. The 40 tested strains belonging to 8 species were isolated from hospitalized patients. Against Gram positive cocci, Ciprofloxacin (CPLX) and ofloxacin (OFLX) were the more active and nefloxacin (NFLX) was less potent than the others. Against Ps. aeruginosa, CPLX had the highest activity, enoxacin (ENX) as well as OFLX had powerful activity, whereas NFLX was less active. All the 4 agents showed high activity against Gram negative bacilli. In the self controlled, randomized crossover study, 4 fluoroquinolones were given to 10 healthy volunteers and then SBAs were determined using microdilution method. The peak SBAs of CPLX and OFLX were significantly higher than NFLX, and those of ENX were comparatively low, but there was no difference between ENX and OFLX against most of the strains tested. The percentages of peak SBAs greater than 1:8 of the 4 fluoroquinolones suggest that in the treatment of serious infections, CPLX and OFLX are more effective and ENX can also achieve high cure rate. The trough SBAs of the 4 fluoroquinolones suggest that the time interval of administration of CPLX and OFLX should be more than 8 hours, but increase of the dosage or shortening of the time interval between the administrations is recommended for ENX and NFLX. PMID- 1451554 TI - Abdominal pain, ascites, jaundice and oliguria. PMID- 1451555 TI - No epidemics despite devastating floods. PMID- 1451556 TI - Characteristic changes of DNA stemlines during hepatocarcinogenesis in rats. AB - DNA stemlines of hepatocellular carcinoma (HCC) model of adult Wistar rats established by diethylnitrosamine were quantitatively measured by flow cytometry. The cancer-inducing course was divided into four stages, eg, precirrhosis stage, cirrhosis stage, early cancer stage and cancer progression stage. The advantageous DNA stemline of hepatocytes of normal adult Wistar rats was tetraploid (4C). It was from the cirrhosis stage that atavistic proliferation of hepatocytes with diploid (2C) DNA stemline started and replaced 4C hepatocytes, resulting in a new advantageous population. The features of early cancer stage were formation of HCC with 2C DNA stemline, whereas during the cancer progression stage, HCC cells with aneuploid (AN) DNA stemline presented the advantageous growth. The study clearly shows the change pattern of DNA stemline during the course of hepatocarcinogenesis from 4C-2C-AN, which is believed to be the biokinetic mechanism of the development and progression of HCC. PMID- 1451557 TI - Prevalence of antibodies to hepatitis C virus in Chinese patients with viral hepatitis and hepatic failure. AB - Anti-HCV assay with ORTHO kits was done in 100 blood donors and recipients and 374 cases of viral hepatitis, including 65 cases of fulminant, subacute and chronic hepatic failure. None of the 100 blood donors and recipients showed positive anti-HCV response. Anti-HCV was positive in 7.6% of the patients with chronic persistent hepatitis, 9.7% of the patients with chronic active hepatitis and 23.1% of the patients with liver cirrhosis. High prevalence of anti-HCV was observed in subacute hepatic failure (60.8%) and chronic hepatic failure (53.9%). Fifty-two (83.9%) of 62 anti-HCV positive cases were infected concurrently with HBV. The incidence of HBV replicating marker in patients with HCV or co-infected with HBV was lower than that of those with HBV alone. It is suggested that HCV might inhibit the replication of hepatitis B virus. The mortality rate of patients with anti-HCV positive hepatic failure was higher than that of those with HBV infection. Therefore, anti-viral therapy for anti-HCV positive hepatic failure should be considered. PMID- 1451558 TI - Myeloid and erythroid hemopoiesis supported by human bone marrow fibroblasts in vitro. AB - The passages 0 and 3 purified human bone marrow fibroblast layers (FLs) were established by long-term liquid cultures. After 12-day coculture of stromal. cell depleted marrow cell suspensions with passage 0 FLs, 68.33 +/- 4.04% of the hemopoietic colonies adhered to FLs was myeloid in nature and the other 31.67 +/- 4.04% was erythroid. There were still CFU-E (colony forming unit-erythroid), BFU E (burst forming unit- erythroid), and CFU-GM (colony forming unit granulocyte/macrophage) among the nonadherent cells. The media conditioned by passage 0 (F0-CM) and passage 3(F3-CM) FLs stimulated the growth of myeloid and erythroid (BFU-E) colonies. From these data, it is concluded that both FLs and the media conditioned by fibroblasts can stimulate myeloid and erythroid hemopoiesis. PMID- 1451559 TI - Effect of gluco- and mineralocorticoids on gene expression of atrial natriuretic peptide by rat atria in vivo. AB - The effect of gluco- and mineralocorticoids on atrial natriuretic peptide (ANP) gene expression as well as plasma sodium and potassium concentrations was studied in both intact and adrenalectomized Wistar rats. Atria total RNA was extracted with cold phenol method and hybridized to alpha-32P labeled rat ANP-cDNA probe. The ANP gene transcripts in intact rats receiving dexamethasone and in adrenalectomized rats receiving both dexamethasone and deoxy-corticosterone increased by twofold, while there were no significant changes in the other groups. There were no parallel correlations between the rise of corticoid hormones-induced plasma Na+ concentration and the enhancement of rANP-mRNA level. The results suggest that glucocorticoids, when used together with mineralocorticoids, may directly increase ANP gene expression, whereas administration of mineralocorticoids alone has no effect on ANP gene expression. PMID- 1451560 TI - Surgical treatment of cervical spine tumors. AB - Of 40 patients with cervical spine tumor treated from 1980 to 1990, 24 had a primary tumor and 16 a metastatic tumor. Thirty-four patients were operated on through anterior and 5 through posterior approach. Preoperative neck pain was relieved and muscular strength of shoulder and arm increased after operation. Total excision methylmethacrylate or metal prosthesis replacement was used. Total excision of the lesion was emphasized for preventing the recurrence of the tumor. Indications and aims of the operation are discussed. PMID- 1451561 TI - Oculomotor neuropathy syndrome. A diagnostic challenge in nasopharyngeal carcinoma. AB - Of 22 patients with different kinds of oculomotor neuropathy syndrome (ONS), 18 were initially suspected of suffering from nasopharyngeal carcinoma (NPC). However, in a series of evaluations, their diagnoses eventually proved to be other diseases such as cranial neuritis, aneurysm of intracranial internal carotid artery, chordoma, etc. The remaining four patients initially diagnosed as having aneurysm of skull base or pituitary lesion were actually NPC sufferers. Therefore, one should be very careful in differentiating NPC from many other diseases contributing to the similar manifestation of ONS. PMID- 1451562 TI - Evaluation of penetrating keratoplasties with long-term cryopreserved corneas using simplified method. AB - Since March 1986, the authors have studied and simplified the corneal cryopreservation technique using a self-made QL Bio-freezer. On the basis of successful animal experiments, penetrating keratoplasties with human cadaver corneas cryopreserved 9 to 571 days (averaging 131 days) were performed in 60 patients (61 eyes). The patients were followed up for 1.5 to 50 months. 41 of the corneal grafts remained clear, 9 became translucent and 11 cloudy. A total of 46 eyes had their visual acuity improved significantly. The results show that clinical use of corneal cryopreservation by the simplified two-step method is noteworthy. PMID- 1451563 TI - Ultrastructures of the glial epiretinal membrane induced by activated macrophages. AB - A rabbit model of glial epiretinal membrane was established following the injection of activated macrophages into the vitreous. The membrane was composed entirely of cells with glial characteristics, ie, abundant intermediate filaments, microvilli, junctional complexes and basement membranes. The extracellular matrix of the mature membranes contained collagen fibrils of 10 to 15 and 20 to 25 nm in diameter. Fusiform densities were seen adjacent to the cell membrane and cells with indented nuclei were found in thick membranes. These observations demonstrate that glial cells in epiretinal membranes may synthesize collagen and possess myofibroblast-like properties. PMID- 1451564 TI - Functional compartments in the portal system. An experimental study. AB - The pressure of the portal trunk, the left gastric vein, the left and right gastroepiploic veins, the mesenteric vein and the abdominal aorta was measured experimentally at the same time in 10 normal dogs. The levels of the raised pressure in the different compartments with their outflow tracts obstructed respectively were observed and the potentials of the functional barriers between these compartments were quantitatively evaluated. The findings showed that the average power of the functional barriers was 45.1 +/- 5.7% between the different compartments in the gastrosplenic area and 74.3% in the mesenteric region. The weakness of the functional barriers' capacity limiting the collateral diversion between the lesser and greater splanchnic systems may be one of the causes making the distal splenorenal shunt lose its selectivity. PMID- 1451565 TI - Syndrome of endemic arsenism and fluorosis. A clinical study. AB - Sixty-five patients in Xinjiang with syndrome of endemic arsenism and fluorosis (SEAF) were investigated clinically from March 1982 to August 1989. SEAF is a kind of chronic syndrome resulting from the combined, harmful effects of two trace elements, arsenic and fluorine. Peripheral neuritis and cardiovascular changes were observed in this syndrome more often than in simple arsenism or simple fluorosis. The excessive quantities of these two trace elements in blood might have a synergic, harmful effect on the nervous and circulatory systems. No definite conclusion could be reached with regard to the morbidity of skin and visceral tumors in this series. The incidence of associated skin cancer was found to be 7.7% and an associated Grade II squamous cell carcinoma of the esophagus was encountered in one patient. PMID- 1451566 TI - Biokinetics of tritium incorporation into the tissues of rats during continuous ingestion of tritiated water or tritium-labeled food. AB - Wistar strain male rats were continuously given tritiated water or tritiated wheat as drinking water or food for 70 days. During the ingestion, the tritium incorporation into rat tissues was examined in both wet and dry samples of liver, kidney, testis and blood. The concentration of organically bound tritium (OBT) in dry tissues of rats exposed to tritiated water (HTO) and 3H-food (tritiated wheat) attained an equilibrium within 2-3 weeks after the exposure. The concentration of OBT in dry tissues of rats exposed to HTO also reached an equilibrium within 3-4 weeks after the exposure. However, rats exposed to 3H food, except for the liver, such an equilibrium state was not reached in other tissues and the OBT concentrations increased gradually throughout the exposure. The relative concentrations of total 3H and OBT at the end of the chronic ingestion of 3H food (70 day), expressed in percentages of the total activity were 1 and 9 times higher than those in rats exposed to HTO, respectively. In both groups, OBT as well as total 3H was almost uniformly distributed among the tissues examined. PMID- 1451567 TI - Pheochromocytoma: dizziness, palpitation, abdominal pain and vomiting. PMID- 1451568 TI - National epidemiological survey of blindness and low vision in China. AB - According to the National Sample Survey of Blindness and Low Vision, the prevalence of blindness in China was 0.43%, resulting chiefly from cataract (41.06%), corneal diseases (15.38%), trachoma (10.87%), and glaucoma (8.80%); and the prevalence of low vision in China was 0.58%, of which the main causes were cataract (49.83%), ametropia/amblyopia (14.98%), trachoma (9.55%), corneal diseases (8.48%), chorioretinal diseases (6.27%), etc. Among children under 14 years of age, the leading cause of blindness and low vision was heredity (48.46%). Among elderly of 60 years and over, the leading cause of blindness and low vision was cataract (73.13%). PMID- 1451569 TI - Treatment of hemophilia A by living mother-to-son splenic transplantation. First case report in the world. AB - A case of severe hemophilia A was treated by living mother-to-son splenic transplantation. The recipient was a 9-year-old boy. After splenic transplantation, the level of blood factor VIII:C was increased, and no spontaneous hemorrhage occurred. The boy was followed up for over two years. This is a case of spleen allotransplantation with the longest function in the world. PMID- 1451570 TI - Electrophysiological analyses of serotonergic actions on neurons in hypothalamic ventromedial nucleus in vitro: receptor subtypes involved and implications for regulation of feeding and lordosis behaviors. AB - Previously, we have shown that serotonin (5-HT) can inhibit, excite, or biphasically inhibit and excite individual neurons of the ventromedial nucleus (VMN) in hypothalamic slices from female rats. In the present study, similar in vitro methods were used to further characterize VMN neurons responsive to 5-HT, and to identify the receptor subtypes involved in mediating these 5-HT actions. Results from a dose-response experiment indicate that increasing the dose of 5-HT can transform an inhibitory response into a biphasic or even an excitatory response. This indicates that modulation of 5-HT release in the VMN could alter the net response of the VMN to this transmitter. By comparing the actions of 5-HT with the effects of selective agonists and antagonists, the inhibitory action was found to be mediated predominantly, if not exclusively, by 5-HT1A receptors, while the excitatory action was mediated predominantly or exclusively through 5 HT2 receptors. There appear to be few, if any, 5-HT3 receptors in the VMN, and their functions are unclear. The inhibitory and the excitatory phases of the biphasic responses were not mediated together by a single receptor subtype but were mediated separately by 5-HT1A and 5-HT2 receptors, respectively. The presence of the biphasic response in a large proportion of neurons, therefore, indicates the coexistence of different subtypes of 5-HT receptors in many individual VMN neurons. The use of selective agonists and antagonists further indicates that the coexistence also occurs in neurons showing monophasic responses, and that the opposite actions mediated by the coexisting receptor subtypes can interact with each other. Therefore, changing the ratio of coexisting receptor subtypes could modify the net output of the VMN response to 5 HT. Together with behavioral studies by others, it emerges from our findings that the inhibitory action of 5-HT on VMN neurons is associated with, and may be responsible for, the stimulation of feeding and inhibition of lordosis, while the excitatory action is related and may lead to the opposite behavioral effects. Finally, with the coexistence in VMN neurons of two receptor subtypes that can mediate 5-HT effects on both feeding and lordosis, the VMN can serve as a substrate for 5-HT to coordinate these two behaviors. PMID- 1451571 TI - Vasodilator and oxidant scavenger in the neurogenic pulmonary edema induced by cerebral compression. AB - In vagotomized rats, cerebral compression (CC) produced marked increase in arterial pressure and pulmonary hemorrhagic edema (PHE). We studied the effects of a vasodilator and an oxidant scavenger to delineate the role of hemodynamic and permeability factors in this type of neurogenic PHE. Infusion of sodium nitroprusside at a dose of 5 micrograms/kg/min significantly reduced the CC induced pressor response by 14% and the lung edema by 41%. A dose of 10 micrograms/kg/min blocked the pressor response by 51%, and completely prevented the lung injury. Dimethylthiourea (DMTU), a potent scavenger for oxidants such as hydroxyl radical and hydrogen peroxide, in doses of 300 and 600 mg/kg was pretreated 15 min before CC. Although DMTU was shown to block the permeability lung damage caused by phorbol myristate acetate (a neutrophil activator), this agent did not exert any effect on the CC-induced pressor response and lung injury. The data indicate that granulocyte-mediated oxidants such as hydroxyl radical and hydrogen peroxide do not appear to be involved in this type of neurogenic lung pathology. The results support the concept that PHE induced by intracranial hypertension is initiated by hemodynamic changes in the systemic and pulmonary circulation. Hydrostatic effect plays a major role in this type of neurogenic lung pathology. PMID- 1451572 TI - Effects of intra-raphe injection of amino acids on cardiovascular function in rats. AB - The effects of microinjection of an excitatory amino acid (glutamate, 10 micrograms) or several inhibitory amino acids (taurine 10 micrograms, GABA 10 ug or glycine 10 ug) into the dorsal raphe region on cardiovascular function were assessed in rats under pentobarbital sodium. Intra-raphe administration of glutamate, but not saline, caused an increase in the mean arterial pressure. By contrast, intra-raphe administration of taurine, GABA or glycine, but not saline, caused a decrease in both the mean arterial pressure and the heart rate. The glutamate-induced hypertension or both the hypotension and the bradycardia induced by taurine, GABA or glycine was antagonized by pretreatment with intra raphe injection of a serotonergic receptor antagonist (1 ug cyproheptadine). In addition, the vasopressor and bradycardia responses to an intravenous dose of epinephrine (2.5 ug/kg) were assessed in saline-treated rats and amino acid treated rats. Intra-raphe injection of glutamate produced a significant decrease in reflex bradycardia compared to the controls. On the other hand, administration of taurine, GABA or glycine into the dorsal raphe region led to an enhancement of epinephrine-induced bradycardia. Again, the reduction or the facilitation of the epinephrine-induced bradycardia following administration of these amino acids was antagonized by pretreatment with cyproheptadine. The results suggest that the serotonergic receptor mechanisms in the dorsal raphe region play a role in the elaboration or modulation of the cardiovascular responses to amino acids (including glutamate, taurine, GABA and glycine). PMID- 1451573 TI - Antidiuresis and natriuresis induced by gastric distension in water-loaded rats. AB - Antidiuretic and natriuretic responses were observed following gastric distension in anesthetized, water-loaded rats. An increase of intragastric pressure to 25, 30, 35, and 40 cm H2O of 2-minute duration respectively elicited 11, 35, 45, and 55% inhibition of water diuresis with concomitant, graded increase of sodium excretion by the kidney. These antidiuretic and natriuretic responses to gastric distension persisted and sustained the same intensity after acute bilateral cervical vagotomy, indicating that the sensory input conveyed from the gastric mechanoreceptors to central nervous system during gastric distension should involve afferent fibers other than vagus nerve. Rats with diabetes insipidus (D1) produced by hypothalamic lesions were also tested, but neither antidiuresis nor natriuresis in response to gastric distension was observed in these D1 rats whose neurohypophysis contained little antidiuretic hormone (ADH). In conclusion, gastric distension may induce liberation of ADH and probably other neurohypophysial hormone which affects renal handling of sodium and water in anesthetized, water-loaded rats. PMID- 1451574 TI - Effects of thyroidectomy on the hematocrit and blood viscosity in ovariectomized rats. AB - The hematocrit and blood viscosity were measured in ovariectomized (Ovx) rats following thyroidectomy or sham operation. Rats were thyroidectomized (Tx) or sham Tx immediately after ovariectomy. Three months later, Ovx, Ovx+Tx, and intact rats at proestrus stage were bled. Blood was collected by heart puncture in rats under ether anesthesia and heparinized. One month after the first bleeding, Ovx and Ovx+Tx rats were bled once again. the viscosity of whole blood and plasma was measured at various shear rates at 37 degrees C by means of a Mooney-Ewart viscometer. The hematocrit was determined by a microhematocrit centrifuge. The plasma osmolality was measured by a computerized micro-osmometer. Concentrations of plasma sodium and potassium were measured by a flame photometer. The concentration of plasma thyroid stimulating hormone (TSH) was measured by a radioimmunoassay. In Ovx+Tx rats, the plasma TSH concentration was higher, but the hematocrit and blood viscosity were lower than those in Ovx and proestrus rats. The levels of plasma sodium, osmolality and viscosity were not altered by ovariectomy and thyroidectomy. These results suggest that the lower blood viscosity in thyroidectomized rats is due to a reduction of hematocrit. PMID- 1451575 TI - Influence of temperature on rheology of human erythrocytes. AB - The effect of variation in temperature on the rheological properties of human red blood cells was studied by determining the cell deformation in response to aspiration pressure applied via a micropipette. The time history of the deformation was analyzed by the use of a Voigt viscoelastic model consisting of an elastic element (E) in parallel with a viscous element (eta). Viscosity values were obtained during the initial rapid deformation phase (phase I), the later slow deformation phase (phase II), and the recovery phase. With a rise in temperature from 0 to 45 degrees C, both E and eta values decreased. A thermotropic transition temperature was found at approximately 21 degrees C for phase I viscosity and at approximately 9 degrees C for viscosity in the recovery phase, but not for phase II viscosity. These responses to temperature variations provide insights into the viscoelastic properties of the erythrocyte membrane. PMID- 1451576 TI - Cardiovascular effects of endothelin in chronic hypoxic rats. AB - This study was undertaken to investigate the effects of endothelin (ET) on cardiovascular function in chronic hypoxic rats (HA) and sea level controls (SL). Catheters were placed in femoral and pulmonary arteries for measurements of mean systemic arterial pressure (Psa) and mean pulmonary arterial pressure (Ppa). The cardiac output was measured by thermodilution method. It is very interesting to find that intravenous injection of ET (0.2 and 1 nmol/kg) caused a decrease in pulmonary arterial pressure (from 44 +/- 2.6 to 36 +/- 1.9 mmHg, p < 0.05) which sustained for about 10 min while the systemic arterial pressure rise (1 nmol/kg) or no significant change (0.2 nmol/kg) in the HA rats. The depressor action of ET is mainly resulted from the drop of cardiac output in HA rats, since the pulmonary vascular resistance resisted to the action of ET in those chronic hypoxic rats could be due to a simple loss of reaction to ET or the release of vascular dilators which balance the ET vasoconstrictive action. This report also found indomethacin and saralasin did not involve the action of ET on pulmonary arterial depression. PMID- 1451577 TI - [Advances in the prevention of liver neoplasms in China]. PMID- 1451578 TI - [Combined use of glucose and rest period between noise exposure to reduce noise- induced hearing loss]. AB - This paper reports the way which protects hearing from harmful effects of noise. 67 guinea pigs were divided into four groups, 8-9 guinea pigs in each group. The total time of noise exposure at 125 dB SPL white noise in each group was one hour. The control was exposed continuously for 1 hour. Group I was exposed to noise for 30 minutes after intraperitoneal injection of glucose at 2 mg/g body wt., then rest for 30 minutes and exposed for 30 minutes again. Group II was exposed continuously to noise for 1 hour after intraperitoneal injection of glucose at 2 mg and 4 mg/g body wt. Group III was exposed to noise for 30 minutes, rested for 30 minutes and exposed for 30 minutes again without glucose injection. The auditory brain stem response (ABR) was measured before, immediately, 3 days, and 7 days after noise exposure. The effect on hearing conservation was evaluated according to ABR threshold. We observed that the auditory threshold in group I was significantly lower than that of the control in the given time after noise exposure (P less than 0.05), but not so in group II and III. Combined use of glucose and rest period between noise exposure was able to decrease the threshold shift by 15 dB and 10 dB immediately and 7 days after noise exposure respectively. PMID- 1451579 TI - [Studies on metabolism of a fungicide yekuling in rat]. AB - The metabolism of a fungicide Yekuling was studied in rat after oral administration. Four metabolites were isolated and purified by means of reverse phase HPLC and TLC. They were identified to be acetic acid, 1,3-dithiolan-2 ylidenehydrazide; pyruvic acid, 1,3-dithiolan-2-ylidenehydrazide; benzoic acid and hippuric acid with UV and MS. The latter was further confirmed by chemical synthesis. The experimental results showed that Yekuling was metabolized extensively in rat. Yekuling was hydrolyzed by amidase to produce benzoic acid and 1,3-dithiolan-2-ylidenehydrazide. The latter was further acetylated by N acetyltransferase to form acetic acid, 1,3-dithiolan-2-ylidenehydrazide, or condensed spontaneously to form pyruvic acid, 1,3-dithiolan-2-ylidenehydrazide. Benzoic acid was further conjugated with glycine to produce hippuric acid. PMID- 1451580 TI - [Biomechanics study during march with different military equipment of equal carrying load]. AB - The purpose of the study is to select the best military equipment of equal carrying load by the index of biomechanics. Six healthy young men whose age varied between 19 and 25 years were volunteered, in the experiment. They were required to march 1.5 h, carried with different military equipment of equal weight, 25 kg, at a speed of 5 km/h. The centre of gravity of the body and its kinesic parameters were measured before and after the march. The frequency and length of pace were measured during the march. The results of the study indicated that the displacement of the body's centre of gravity carrying equipment I was the most evident, whereas the least displacement of centre of gravity of the body was that carrying equipment II. The frequency of pace during the march was reduced in all three carrying different kinds of equipment, the most evident being that carrying equipment I; the length of pace became bigger with those carrying equipment II and III; the speed of pace was decelerated using equipment I, but it was quickened with equipment II. The change of kinesic parameters have no significant difference among the three. In summary; equipment II conforms best to biomechanical principles, whereas equipment I is the worst. PMID- 1451581 TI - [A study on lymphocyte subpopulations and immunologic status of female workers exposed to benzene]. AB - Peripheral blood from 29 female subjects occupationally exposed to benzene for an average duration of 8.6 years were analysed with monoclonal antibodies (McAbs). Acid alpha-naphthyl acetate esterase (ANAE)-positive cells among lymphocytes and serum IgG, IgA and IgM levels were determined simultaneously. The results showed a decreased total number of lymphocytes, reduction of percentages and absolute numbers of both CD2+ and CD4+ cells, decreased CD8+ and CD57+ cell numbers without significant changes in their percentages, a decreased CD4+/CD8+ ratio, an increased CD20+ cell percentage without significant change in its absolute number and a decreased serum IgM level. ANAE(+)-cell percentages of lymphocytes were of marked positive correlation to CD2+ cell percentages. These results indicate that benzene can cause immunosuppressive effects to the exposed subjects and the analysis of lymphocyte subpopulations by means of McAbs may be useful for evaluating early adverse health effects on workers exposed to the toxicant. PMID- 1451582 TI - [Experimental study of antagonizing effect of calcium and magnesium against fluoride toxicity in collagen]. AB - SD rats were given fluoride 20 mg/kg for 14 days through a gastrointestinal tube, body weight growth depressed obviously, the ratio of the Liver and Kidney weight to body weight increased significantly, hemoglobin concentration dropped and morphology and metabolism of collagen all became abnormal. All these effects can be antagonised by giving calcium (100 mg/kg), magnesium (100 mg/kg) or calcium and magnesium combined (50 mg/kg each). When Ca and Mg is given combined, the antagonizing effect is even better. PMID- 1451583 TI - [Inhibition of eight natural foods on mutagenic effect by aflatoxin B1 and extracts of fungi]. AB - Eight natural foods were tested for their antimutagenic activities on AFB1, metabolic extracts of A. versicolor and A. ochraceus which induced mutagenic activity in TA 98 and TA 100 mutants. The tested substances were extracted repeatedly with acetone. The revertance induced by AFB1, metabolic extracts of A. versicolor and A. ochraceus were significantly decreased when the eight natural foods were added into the medium. The results showed that the eight natural foods had different degrees of anti-mutagenic effect in vitro, suggesting that anti mutagenic substances were present in these natural foods. It is considered that these foods may be practically valuable in the chemoprophylaxis of liver cancer in men. PMID- 1451584 TI - [The effects of kitchen air pollution on animals immune function]. AB - The paper determined the activity of mitogenic response of T lymphocyte, NK cell activity and lymphocyte IL-2 production activity after the mice had been exposed to the polluted kitchen air. The results showed that these immune functions were inhibited in descending order in the mice exposed to pollutants from burning coal mixed with oily smoke. PMID- 1451585 TI - [Multivariate analyses of causal factors included cooking oil fume and others in matched case-control study of lung cancer]. AB - This paper reports the study of 1:1 matched case-control for eighty-three cases of primary lung squamo-carcinoma and seventy-one cases of primary lung adenocarcinoma from urban districts of Nanjing. The result of conditional analysis reveals that cooking oil fume is a common risk factor for lung squamo carcinoma and adenocarcinoma. Its relative risk and population attributable risk (%) are 3.8138, 3.4466 and 51.56%, 60.99% respectively. Besides, smoking, family history of tumors, fuel types and keeping warm by coal stove in winter are selected as risk factors for lung squamo-carcinoma, while history of chronic bronchitis and family history of tumors are screened as risk factors for lung adenocarcinoma. Summary population attributable risk for all five factors of lung squamo-carcinoma and all three factors of lung adenocarcinoma are 99.47% and 76.65% respectively. PMID- 1451586 TI - [A SOS induction test screening study for vegetables inhibiting mutagenicity caused by antineoplastic drugs]. AB - Using mutational and anti-mutational synchronous in SOS inductest (+/- S9), We found that 7 out of 11 kinds of commonly eaten vegetables had the ability to inhibit mutagenicity caused by chemical drugs such as Mitomycin C, Bleomycinia, Fluorouracil, Cis-Diaminodichloroplatinum, Arabinosylcytosin and mustargen, They were garlic, green Chinese onion, onion, garlic bulb, tomato, cucumber and water radish. The other 4 lacking this ability were rape, chinese toon, ginger and asparagus lettuce stalk. We believe that our results can be helpful in the preparation. of cancer patients' diet, who are receiving chemotherapy and in the prevention of cancer. PMID- 1451587 TI - [The confidence interval of micronuclei and chromosome aberration induced by radiation]. AB - This paper proposes a revised method of determining confidence interval of population rate based on statistical theory. The confidence interval of population rate can be obtained accurately by using this method. In addition, it includes a discussion of confidence interval about some basic indexes of micronuclei and chromosome aberration induced by radiation. PMID- 1451588 TI - Preparation and microscopic visualization of multicolor luminescent immunophosphors. AB - The preparation of charge-stabilized suspensions of small phosphor particles (0.1 0.3 micron) and their coupling with antibodies to immunoreactive conjugates is described. Phosphor particles consisting of yttriumoxisulfide activated with europium served as a model system in the evaluation of the stabilizing properties of several polycarboxylic acids. The optimal reagents were then applied to other phosphors which differ in spectral characteristics as well as in luminescence lifetime. These phosphors were ground to a size of 0.1-0.3 micron and proteins or other macromolecules were adsorbed to the phosphor particles to prepare conjugates of different physico-chemical properties. A time-resolved microscope, suitable for real time visualization of the time-delayed luminescence of the immunophosphors by the human eye, is described in detail. Since most phosphors require excitation with far UV light, a special fluorescence microscope allowing far UV excitation was developed for conventional visualization of the luminescence emitted by the phosphor. The possibility of multiple color labeling using various phosphor conjugates was demonstrated in a model system consisting of haptenized latex beads. PMID- 1451589 TI - Quantification by laser scan microscopy of intracellular doxorubicin distribution. AB - Changes in intracellular drug localization accompany doxorubicin resistance in multidrug resistant tumor cells. The purpose of this study was to develop a method to quantify these changes and so detect different levels of resistance. Tumor cells were incubated with the fluorescent anthracycline doxorubicin (excitation at 480 nm; emission maximum at 560-590 nm) and were quantified using laser scanning microscopy. The fluorescent mode was used to record the intracellular drug distribution, whereas the absorption mode was used to define the nuclear and cytoplasmic boundaries. The cell compartments were delineated interactively on an image processing system and the ratio nuclear fluorescence/cytoplasmic fluorescence (N/C ratio) was determined. N/C ratios were: 1.8 in the Chinese hamster ovarian cell line AUXB1 and 0.1 in its MDR subline CHRC5; 3.8 in the human squamous lung cancer cell line SW-1573 and 1.8 and 0.4 in its MDR sublines SW-1573/2R120 and SW-1573/2R160, respectively; and 3.6 in the human myeloma cell line 8226/S and 2.1 and 1.0 in its MDR sublines 8226/Dox4 and 8226/Dox40, respectively. The doxorubicin distribution was independent of the doxorubicin concentration within a range from 1-32 microM. Furthermore, the progressive mean of the nuclear/cytoplasmic doxorubicin fluorescence ratio showed that a minimal sample size of 30 cells is necessary for reliable results. The results of two independent assessments showed a high reproducibility (r = 0.97). Thus, with the method described in this paper, it is possible to detect relatively low levels of doxorubicin resistance (factor 8). PMID- 1451590 TI - Image cytometric DNA analysis in human breast cancer analysis may add prognostic information in diploid cases with low S-phase fraction by flow cytometry. AB - Measurements of DNA ploidy can be performed either with image cytometry (ICM) or flow cytometry (FCM); both methods provide independent prognostic information in primary breast cancer. The aim of the present investigation was to compare the two methods and to relate the findings to prognosis (median follow-up 42 months). Concordance in ploidy status (diploid, tetraploid, aneuploid) was obtained in 76% of the samples (168/222). When the fraction of S-phase cells (SPF) from FCM analysis was also taken into consideration, four different groups of samples were obtained (Flow I-IV), which were considered to correspond to the Auer classification (Auer I-IV) of DNA histograms obtained from image cytometry. Complete concordance between the two techniques now was 70% (155/222). Samples classified as Flow I (diploid or near-diploid with low SPF) and Auer I had a distant metastasis rate of 3/60 (5%), as compared to 62/154 (40%) for all other combinations of the Flow and Auer classifications taken together. Thus, the only findings of prognostic importance were that some samples were Flow I but not Auer I, or vice versa. These two groups represent 17 (7.7%) and 14 (6.3%), respectively, of the total number of samples, and had frequencies of distant metastasis similar to those of the other high-risk groups, namely, 7/17 and 5/14, respectively. In a multivariate analysis, flow cytometric S-phase value was a stronger prognostic factor than either the Flow and Auer classification. We conclude that when routine FCM DNA analysis is used, diploid or near-diploid samples with a low S-phase value should be reanalyzed with ICM. PMID- 1451591 TI - Methods for topographical analysis of intra-nuclear BrdUrd-tagged fluorescence. AB - The observation of BrdUrd staining in the nuclei of cells from exponentially growing populations reveals different typical replicating patterns. We propose a methodological approach to order and characterize BrdUrd intranuclear distributions. First, visual ordering of the patterns is assessed using a spectral analysis coupled to a k-nearest neighbors clustering technique. Subsequently, nine topographical features are introduced to characterize the spatial distribution of BrdUrd-tagged fluorescence in the nuclei of proliferating cells. These topographical features are based on a structural approach. The localization of fluorescence spots is expressed in terms of the normalized distance from the nuclear border and its standard deviation. These topographical features are simple to calculate and easy to relate to visual experience. PMID- 1451592 TI - Eukaryotic DNA replication is a topographically ordered process. AB - This paper describes the relationship between the BrdUrd replicating pattern of a cell and its localization within the S phase by means of topographical features and DNA content measurement. The present study follows an objective ranking of the BrdUrd patterns obtained from a spectral analysis of the BrdUrd images. The pattern ranking was consistent with the DNA content increase throughout the S phase. Five texture groups were arbitrarily set up for the purpose of multivariate analysis. Nine topographical parameters were computed for each BrdUrd-labelled nucleus. The descriptive quality of these parameters was assessed by means of factorial discriminant analysis. These parameters made it possible to characterize objectively the known pattern distributions of replication sites qualitatively described in the literature. PMID- 1451593 TI - Neutrophil function screening in patients with chronic granulomatous disease by a flow cytometric method. AB - Neutrophils from patients with chronic granulomatous disease (CGD) fail to produce a significant oxidative burst following stimulation. We have evaluated the use of flow cytometry and the dye 2',7'-dichlorofluorescein diacetate (DCF) for routine screening for deficiencies of neutrophil oxidative burst. A range for DCF fluorescence for phorbol myristate acetate stimulated and non-stimulated neutrophils was established based on data from 52 healthy adults. Samples from three patients with suspected neutrophil dysfunction, three patients with X linked CGD, and one patient with autosomal recessive (AR) CGD were evaluated with both the DCF assay and the quantitative nitroblue tetrazolium dye reduction (NBT) test. For the DCF test, the ratio of mean fluorescence intensity of stimulated to non-stimulated neutrophils was less than 5 for CGD patients and from 16 to greater than 50 for healthy individuals. With the DCF test, two populations of neutrophils could be identified in samples from four carriers of X-linked CGD, although two carriers of AR CGD had NBT and DCF results in the normal range. Our data suggest the DCF test is a sensitive and convenient method for detecting CGD. PMID- 1451594 TI - Differences between platelet and microparticle glycoprotein IIb/IIIa. AB - Glycoprotein (GP) IIb and IIIa are major constituents of the platelet membrane which are involved in forming the fibrinogen receptor on activated platelets. We used flow cytometry to study the effects of ethylene-diamine tetraacetic acid (EDTA) on the membrane GPIIb/IIIa complexes of platelets and microparticles, and to study the effects of cations on dissociated GP complexes. Microparticles were detected by both the volume signal and by fluorescence using an FITC-conjugated anti-GPIb antibody (NNKY5-5). When platelets were stimulated with ADP, calcium ionophore A23187, or thrombin, fibrinogen binding to the platelet surface increased markedly. However, fibrinogen binding to microparticles showed little increase in response to such agonists. Microparticle GPIIb/IIIa complexes were dissociated by incubation with EDTA at 37 degrees C but did not reassociate after treatment with divalent cations (Ca2+, Mg2+, and Mn2+) in contrast to platelet GPIIb/IIIa complexes. These results suggest that some interaction of GPIIb/IIIa and linked structures like the platelet cytoskeleton may be involved in the reassociation of dissociated GPIIb and GPIIIa, perhaps explaining the failure of reassociation of microparticle GPIIb/IIIa (i.e., the fibrinogen binding to microparticles). PMID- 1451595 TI - Differential analysis of animal bone marrow by flow cytometry. AB - A simple procedure was developed for rapid analysis of animal bone marrow by flow cytometry using the lipophilic cationic dye 3,3'-dihexyloxacarbocyanine iodide [DiOC6(3)]. The batch process allows differentiation of bone marrow cells into lymphoid, erythroid, and myeloid populations and enables classification of erythroid and myeloid cells into proliferating and maturing subpopulations. From these data, myeloid:erythroid (M:E) ratios and maturation indices for erythroid and myeloid cells (EMI and MMI, respectively) can be derived. This procedure provides the opportunity to analyze bone marrow quantitatively and offers distinct advantages to current manual methods in terms of simplicity, throughput, and reproducibility. The method has been tested successfully using marrow from Wistar rats, B6C3F1 mice, beagle dogs, and cynomolgus monkeys. This technique facilitates the evaluation of bone marrow samples taken from preclinical safety studies or from animal colonies of large size. PMID- 1451596 TI - Drop-delay measurement using enzyme-coated particles. AB - A simple technique is suggested for the measurement of drop delay for flow sorting. While the flow cytometer was set to sort a fixed number of particles, the drop-delay setting was changed step by step, and at each step the HRP-coupled particles were sorted into a well of an immunoassay strip. Then the HRP activity of the sorted samples was revealed by routine methods. The maximum level of the enzyme activity shows the proper drop-delay setting. Determination of the drop delay setting takes only a few minutes. The technique is independent of the type of flow cytometer and does not require any additional equipment. PMID- 1451597 TI - Protooncogene expression in subpopulations of cells from leukemia patients. AB - This report describes a method for preserving the light scatter patterns of cells in which myc and myb expression are being measured. Exposure of cells to 1% paraformaldehyde for 72 h prior to antibody staining for myc and myb proteins preserved the light scatter patterns. Using this method, myc and myb expression was found to be highest in lymphocytes and monocytes and lowest in granulocytes. The measurement of differences in the level of expression of these genes in subpopulations of leukemia cells obtained from individual patients is possible as is assessment of the levels of expression amongst normal and leukemia cells present in the same patient. PMID- 1451598 TI - Flow cytometric analysis of peripheral blood erythrocyte chimerism in alpha thalassemic mice. AB - A rapid and reliable method for longitudinal studies on the degree of red cell chimerism following bone marrow transplantation of alpha-thalassemic recipient mice is presented. Blood obtained by tail clipping from transplanted mice was analyzed by measuring forward light scatter (FLS) distribution of red cells using a flow cytometer. Amplification and threshold of FLS were specifically adjusted. For flow cytometric analysis, the red cells needed to be suspended in hypotonic saline (103 mmol/l NaCl). Osmotic fragility testing showed that lysis of erythrocytes did not significantly influence the measurements. Flow cytometric measurement allowed for a rapid determination of the degree of red cell chimerism. PMID- 1451599 TI - Flow cytometric measurement of lipid peroxidation in vital cells using parinaric acid. AB - A method for measuring lipid peroxidation using time resolved flow cytometry is described. Because of its chemical nature, the naturally fluorescent fatty acid cis-parinaric acid is readily consumed in lipid peroxidation reactions. It could be loaded into Chinese hamster ovary cells in a time and concentration dependent manner at 37 degrees C, with 5 microM for 60' giving consistent, bright fluorescence without evidence of cytotoxicity. Examination of cells by fluorescence microscopy showed diffuse staining of surface and internal membranes. Cells were maintained at 37 degrees C while being examined in an Epics Elite flow cytometer equipped with a 325 nm HeCd laser, and parinaric acid fluorescence at 405 nm was measured over time. Addition of the oxidant tert-butyl hydroperoxide resulted in a burst of intracellular oxidation, shown by simultaneously loading the cells with dichlorofluorescein, and loss of parinaric fluorescence over time. This was followed by cell death, indicated by loss of forward light scatter and uptake of propidium iodide. Pretreatment of the cells with the antioxidant alpha-tocopherol, 200 microM, reduced the rate of loss of parinaric acid fluorescence and delayed the onset of cell death. Simultaneous biochemical determination of the lipid peroxidation breakdown product malondialdehyde confirmed a close temporal relationship with loss of parinaric acid fluorescence, both with and without alpha-tocopherol pretreatment and suggested that the flow cytometric assay for lipid peroxidation is of comparable sensitivity. The mitochondrial stain dodecyl acridine orange and the cyanine dye DiOC(6)3 were combined with cis-parinaric acid staining and could be excited by the latter using resonance energy transfer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451600 TI - Signal transduction in monocytes and granulocytes measured by multiparameter flow cytometry. AB - The novel calcium indicator fura red and the oxidative burst indicator dihydrorhodamine (both excited at 488 nm) were used in combination with multiparameter flow cytometry to allow simultaneous kinetic measurements of calcium fluxes and oxidative bursts in monocytes and granulocytes. Using this method it was possible to obtain direct evidence for the following cell type- and stimulus-specific differences in signal transduction pathways: 1) n-formyl methionyl-leucyl-phenylalanine (FMLP)/cytochalasin B-induced oxidative burst is several-fold higher in granulocytes than in monocytes although the calcium fluxes have similar amplitudes in the two cell types; 2) stimulus-induced calcium fluxes in granulocytes are mainly due to release from intracellular stores, whereas monocytes mobilize calcium mainly by influx from the medium; 3) the FMLP/cytochalasin B-induced calcium flux in monocytes is less sensitive to the G protein inhibitor pertussis toxin than the flux in granulocytes; 4) in contrast to FMLP/cytochalasin B, the protein kinase C activator phorbol myristate acetate (PMA) induces an oxidative burst that is not preceded by a cytoplasmic calcium flux; 5) the PMA-induced oxidative burst can be triggered in monocytes and granulocytes that are depleted of intracellular calcium ions, whereas that induced by FMLP/cytochalasin B can not; 6) the G-protein inhibitor pertussis toxin blocks an early event in the signal transduction pathway of FMLP/cytochalasin B, as shown by inhibition of both calcium fluxes and oxidative burst; and 7) 100 nM of the protein kinase inhibitor staurosporine blocks the FMLP/cytochalasin B-induced respiratory burst by interfering with a step downstream to cytoplasmic calcium fluxes, whereas only 10-20 nM is necessary to block PMA-induced oxidative burst. PMID- 1451601 TI - Swine chromosomal DNA quantification by bivariate flow karyotyping and karyotype interpretation. AB - Human and swine chromosomes were analyzed separately and as a mix to obtain bivariate flow karyotypes. They were normalized to each other in order to use the human chromosomal DNA content as standard. Our results led to the characterization of the "DNA line" in swine identical to the human "DNA line." Estimation of the DNA content in mega-base pairs of the swine chromosomes is proposed. Chromosomal assignment to the various resolved peaks on the bivariate swine flow karyotype is suggested from the relation between DNA content quantified by flow cytometry and chromosomal size. Swine chromosomes 1, 13, 6, 5, 10, 16, 11, 18, and Y were assigned to peaks A, B, C, K, L, N, O, Q, and Y, respectively. Peaks D and E were assumed to contain chromosomes 2 and 14, but without specific assignment. Similarly, P and M peaks were expected to correspond to chromosomes 12 and 17. Of the remaining chromosomes (3, 7, X, 8, 15, 9, and 4), chromosomes 3, 7, and X, which were assigned previously to peaks F, G, and H, respectively, led us to deduce that chromosomes 15 and 8 belonged to peaks I and J, and chromosomes 9, 4, and X to peak H. PMID- 1451602 TI - Comparative evaluation of fresh, fixed, and cryopreserved solid tumor cells for reliable flow cytometry of DNA and tumor associated antigen. AB - Five different protocols for the short-term preservation of cells used for multiparameter flow cytometric assay of tumour associated antigens (TAA) and DNA were assessed in cell suspensions prepared by mechanical disaggregation of 15 gynecological tumors. The protocols at 4 degrees C were 1) storage in buffer, 2) storage in 50% methanol, and 3) storage in buffer after formalin fixation. Tissues were also cryopreserved as cell suspensions and tissue blocks. When the TAA expression and DNA histograms of the preserved cells were compared with those in fresh cell suspensions, cryopreservation was found to be the best method: TAA expression was well preserved and there was a good correlation between TAA expression and the quality of the DNA histograms, respectively, in fresh and cryopreserved cells (RS: 0.82-0.91, P less than 0.001 for all TAAs). The cell suspensions preserved at 4 degrees C all showed a significant increase in background fluorescence (P less than 0.05) and a reduction in the TAA specific fluorescence (P less than 0.011). Methanol fixation was better than buffered formalin for the proteins studied, though both gave significantly worse results than cryopreservation. The quality of these cell suspensions and the correlation with TAA measurements in fresh cell suspensions deteriorated progressively with time, particularly if they were stored more than a week. PMID- 1451603 TI - Quantitation of resistance of leukemic cells to cytosine arabinoside from BrdUrd/DNA bivariate histograms. AB - The cytotoxicity of ara-C derives from an inhibition of DNA synthesis after incorporation of ara-CTP into DNA. The rate of DNA synthesis can be determined from the amount of bromodeoxy-uridine (BrdUrd) incorporated into cells after a short exposure to BrdUrd. We developed a computer program to quantify the inhibition of the rate of DNA synthesis by analysis of the distribution of BrdUrd/DNA. Inhibition was evaluated in ara-C-sensitive and resistant cells after incubation with different doses of ara-C. An index of resistance to ara-C (RI) was expressed as the ratio of the amount of BrdUrd incorporated into S phase cells incubated with ara-C to that incorporated in the absence of ara-C. In the ara-C-sensitive and resistant HL60 cells, a linear relationship between RI and log ara-C concentration was observed. Small numbers of slightly resistant cells in mixtures of ara-C-sensitive and resistant cells could be determined using this method, making it suitable for clinical use to test the resistance of leukemic cells to ara-C. PMID- 1451604 TI - Calcein: a novel marker for lymphocytes which enter lymph nodes. AB - Previous studies have identified unique cell surface antigens which are associated with the specific binding of lymphocytes to high endothelial venules (HEV). Evidence is presented in this paper which demonstrates that uptake of the fluorescent dye calcein by lymphocytes represents an additional marker for the lymph node homing subpopulation of lymphocytes. Calcein exhibits a characteristic ability to label lymphocytes differentially into two distinct populations, based on fluorescence intensity, that does not occur with three other structurally related, fluorescein-based dyes. In vivo lymphocyte migration studies revealed that cells displaying the "dull" fluorescence phenotype, although entering all lymphoid organs examined, preferentially homed to the lymph nodes, particularly the popliteal lymph node (PLN). By contrast, lymphocytes displaying the "bright" phenotype were essentially excluded from entering lymphoid organs, where entry is HEV dependent, but were observed entering spleen, where entry is HEV independent. Furthermore, a high proportion (76.5%) of lymphocytes displaying the dull fluorescence phenotype expressed the PLN homing receptor MEL-14. Based on these observations it is suggested that calcein uptake may be a marker for general membrane properties, such as fluidity and plasticity, essential for the passage of lymphocytes through HEV. PMID- 1451605 TI - Flow-cytometric enumeration of micronucleated polychromatic erythrocytes in mouse peripheral blood. AB - A flow-cytometric assay is described that can be used to determine the frequency and the DNA content of micronucleated polychromatic (PCE) and normochromatic (NCE) erythrocytes in mouse peripheral blood. Thiazole orange was used for discrimination between PCEs and NCEs, while Hoechst 33342 was used to detect micronucleated PCEs and NCEs. Up to 70,000 polychromatic erythrocytes can be analyzed in less than 10 min. This corresponds to 150-3,000 micronucleated polychromatic erythrocytes, 90-95% of which are true events as determined with a fluorescence microscope after sorting. Using X-rays as the inducing agent in dose response experiments, a significant increase can be registered at doses of 0.02 Gy. It seems possible that the method will also allow the detection of clastogenic effects of other inducing agents at lower doses than previously possible. PMID- 1451606 TI - Three-dimensional image processing for morphometric analysis of epithelium sections. AB - The reproducible classification of poorly differentiated abnormal epithelium specimens is still a diagnostic problem. The computer-aided method described here improves the differentiation between benign and malignant epithelium specimens. Hematoxylin and eosin-stained sections of normal squamous epithelium, dysplasia, carcinoma in situ, and carcinoma were scanned in a TV microscope system and analyzed by means of image processing methods on a DEC 5000/200 workstation. From the 15-20 microns thick histological sections, 3-5 focus positions in steps of 1 4 microns were scanned. The segmentation of the cell nuclei was performed automatically by color analysis and geometric operations. For each nucleus the best focus level was selected and at this level the center of the cell was calculated. Graph theoretical methods were applied to analyze the morphometry of the epithelium specimens. The minimal spanning tree was computed in the three dimensional (3D) space of the sections with the selected centers of the nuclei as vertices. The best feature found for discrimination of the specimens is the average length of all edges in a tree. In the two-dimensional (2D) analysis we had to accept an error probability of about 20% in differentiation of dysplasia and carcinoma. In contrast to this we differentiated normal squamous epithelium, dysplasia, and carcinoma with a correct classification rate of 100% in the 3D analysis. PMID- 1451607 TI - Automated image detection and segmentation in blood smears. AB - A simple technique which automatically detects and then segments nucleated cells in Wright's giemsa-stained blood smears is presented. Our method differs from others in 1) the simplicity of our algorithms; 2) inclusion of touching (as well as nontouching) cells; and 3) use of these algorithms to segment as well as to detect nucleated cells employing conventionally prepared smears. Our method involves: 1) acquisition of spectral images; 2) preprocessing the acquired images; 3) detection of single and touching cells in the scene; 4) segmentation of the cells into nuclear and cytoplasmic regions; and 5) postprocessing of the segmented regions. The first two steps of this algorithm are employed to obtain high-quality images, to remove random noise, and to correct aberration and shading effects. Spectral information of the image is used in step 3 to segment the nucleated cells from the rest of the scene. Using the initial cell masks, nucleated cells which are just touching are detected and separated. Simple features are then extracted and conditions applied such that single nucleated cells are finally selected. In step 4, the intensity variations of the cells are then used to segment the nucleus from the cytoplasm. The success rate in segmenting the nucleated cells is between 81 and 93%. The major errors in segmentation of the nucleus and the cytoplasm in the recognized nucleated cells are 3.5% and 2.2%, respectively. PMID- 1451608 TI - DNA signal splitting improves detection and analysis of tetraploid populations. AB - Detection of DNA tetraploid populations requires a high index of suspicion at the time of data acquisition and frequently requires subsequent off-line analysis for confirmation, including evaluation of the hypertetraploid region. To analyze these specimens, the flow cytometer operator must run all specimens with the G0G1 peak in low channels or rerun specimens in which tetraploidy is suspected with a lower photomultiplier tube (PMT) voltage or lower amplifier gain setting. Re analysis may not be possible in specimens with few cells. A simple modification to the cytometer allows PMT signal splitting with simultaneous processing of the signal by two different amplifiers. This allows simultaneous acquisition of histograms optimized for both the hypotetraploid and hypertetraploid regions. PMID- 1451609 TI - Molecular approach in spider mites (Acari: Tetranychidae): preliminary data on ribosomal DNA sequences. AB - DNA sequence data were used to examine phylogenetic relationships between six species of economically important Tetranychidae mites: Eotetranychus carpini (Oudemans), E. pruni (Reck), Tetranychus pacificus McGregor, T. mcdanieli McGregor, T. turkestani Ugarov & Nikolski and T. urticae Koch. With primers directed toward conserved elements flanking the target region, the Polymerase Chain Reaction was used to amplify the ITS2 spacer of the ribosomal DNA molecule. The nucleotide sequence of a 300-bp fragment of the ITS2 was determined by direct sequencing and nucleotide divergence used for intra-generic comparison in mites. The resulting phylogenetic tree expressing interspecific relationships in genus Tetranychus agrees with morphological data. The study demonstrates the usefulness of the approach in the assessment of the systematics and evolution of the group. PMID- 1451610 TI - An evaluation of the effectivity of the scrub technique in quantitative ectoparasite ecology. AB - The effectivity of the scrub technique used in quantitative parasite ecology to collect ectoparasites from mammalian skins was evaluated. This was done by reprocessing already scrubbed skins with the alkali digestion technique to remove any remaining parasites. The skins of six adult impala (Aepyceros melampus) ewes were used in the study. The results showed that the scrub technique is variable in its effectivity, and on average removed only 30.2% ectoparasites from the skins. It was also shown that the scrub technique is unreliable and more labour intensive and time consuming than the digestion technique, and should preferably not be used in quantitative studies. PMID- 1451611 TI - Preventing complications in the CAVH patient. AB - Continuous arteriovenous hemofiltration (CAVH) is a recently developed extracorporeal technique for treating the fluid overloaded, critically ill patient. Severe complications can occur during this procedure, including clotting and malfunction of the filter, exsanguination, or fluid and electrolyte imbalance. The critical care nurse who understands the principles of filtration, the concepts of heparinization, and the care and maintenance of the large invasive lines required for CAVH can frequently prevent these complications. PMID- 1451612 TI - Catheter-related sepsis: an analysis of the research. PMID- 1451613 TI - The DCCN education STATPack. Reducing intravascular catheter-related sepsis. PMID- 1451614 TI - Guidelines for selecting a conceptual model of nursing: focus on the individual patient. AB - How do conceptual models help you in clinical practice? How can you select the best model to guide successful interventions for your critical care patients? These authors present three guidelines for selection of a conceptual model for your patient situation. Six case studies of patients requiring critical care nursing demonstrate the fit of the patient's problems and goals for care with particular conceptual models of nursing. PMID- 1451615 TI - Strategies for teaching decision making: discrepancies in cuff versus invasive blood pressures. AB - With advanced technology the nurse has multiple assessment information to consider at once. Sometimes the data from different assessment modes conflicts and the nurse needs to evaluate the discrepancies to determine the most reliable assessment measurement. Teaching nurses clinical decision making is more difficult than before because of this increase in the amount and complexity of the data. These authors show how using an algorithm helps to teach decision making. They describe the use of an algorithm as a teaching tool for a course on evaluating the differences in cuff versus invasive blood pressure readings. PMID- 1451616 TI - A comparison of family needs based on the presence or absence of DNR orders. AB - This investigator found no differences between the needs of family members who selected "Do-Not-Resuscitate" (DNR) orders from those who did not. She suggests reevaluating the assumptions about families who select DNR. PMID- 1451617 TI - Continuing education. PMID- 1451618 TI - Islet cell transplants: putting the cart before the horse. PMID- 1451619 TI - Preparing for college: an interdisciplinary workshop for teens with insulin dependent diabetes mellitus. PMID- 1451620 TI - Diet education for children with IDDM. PMID- 1451621 TI - Evaluation of diabetic patients' home urine glucose testing technique and ability to interpret results. AB - The attention of diabetes educators has focused on home blood glucose monitoring, with little attention being given to the educational needs of patients who choose to perform home urine glucose monitoring. This study assessed patients' urine glucose testing technique and ability to interpret test results. A questionnaire was developed and administered by clinic nurses to 100 adults with diabetes who perform home urine glucose monitoring. Patients selected the urine testing product they used at home and demonstrated the technique using a prepared glucose solution. The nurse recorded whether patients correctly performed each step in the procedure according to product instructions. Results indicated that 61% of patients did not perform the procedure correctly. Patients had difficulty reading package insert instructions, could not correctly read a clock, did not wait the correct amount of time before reading test results, and did not routinely keep written result diaries. This study demonstrates the importance of routine review of home urine glucose testing with the product used at home. PMID- 1451622 TI - Adjusting insulins. AB - The teaching of effective insulin adjustment is a formal process that benefits from being carried out in a standardized way. The unique methods outlined in this report have been taught to people with diabetes for over 8 years. Iterative in nature, the methods are safe and work to achieve specified blood glucose or HbA1c targets. They are designed to accommodate each individual's habits, recognizing that acceptance depends on adapting the medication to the life-style rather than vice versa. New technology was used to mediate insulin adjustments at home. Insulin adjustment of itself, however, is but one of five interdependent factors involved in successful self-management. These include (1) choosing sites of insulin injection; (2) choosing species of origin of insulins to be used; (3) reviewing life-style habits, including diet and exercise; (4) implementing dosage titration; and (5) follow-up. Lack of formalized insulin adjustment methods may be a major reason why many diabetes control programs fail to demonstrate significantly better metabolic control in their patients. PMID- 1451623 TI - A survey of patient preference for insulin jet injectors versus needle and syringe. AB - Many studies have tested the insulin absorption rate and mechanical reliability of jet injectors. However, no published papers have dealt exclusively with patient preference for this method of administering insulin over a period of years. This paper reports the results of a survey done to determine if use of a jet injector for delivering insulin has an effect on acceptance of and adherence to a regimen of multiple doses of insulin. Over the past 15 years, the authors have instructed approximately 70 patients to use various jet injectors. A questionnaire was developed and sent to 75 patients. Of these, 42 completed and returned the questionnaire. Survey results indicate that even though some problems with the injectors were identified, 70% of those responding still preferred to take insulin by jet injector. PMID- 1451624 TI - Comparison of first-generation and second-generation blood glucose meters for use in a hospital setting. AB - This study evaluated and compared a first- and a second-generation blood glucose meter for precision, accuracy, and user preference. Two separate capillary blood glucose fingersticks were performed on 25 outpatients and 60 inpatients with diabetes. Samples were drawn for serum glucose determinations immediately following the capillary fingersticks. Comparison of the Accu-Chek II and Satellite G meters in the outpatient setting gave results similar to the reference laboratory's. When the meters were tested on inpatients, the blood glucose results were significantly higher than those obtained from the hospital laboratory. The Accu-Chek II was more precise than the Satellite G on both normal and high blood glucose samples. Nursing staff indicated preference for the Satellite G because of its quick testing time but not for other preference factors surveyed. Both meters provided more accurate assessments of blood glucose concentration than were obtained from the serum glucose samples routinely processed by our hospital laboratory. Use of a nonfluorinated tube and delayed separation of the sample with resultant glycolysis likely account for this difference. PMID- 1451625 TI - Pancreas transplantation: a University of Minnesota perspective. AB - Because of various difficulties, transplantation is restricted to specific situations. Surgery is considered elective by many insurers, so costs are often borne by the patient. Surgical work-up includes a thorough evaluation of diabetes related complications, tissue typing, psychological state, and social issues. Options of cadaver versus living related donors are explored. The surgical procedure is lengthy and the hospital stay long and intensive. Once a patient is ambulatory, education is begun to meet the extensive learning needs. After discharge, surgical follow-up focuses primarily on blood chemistries, medication doses, and surgical complications. Medical follow-up includes monitoring for infections and rejection as well as addressing long-term complications of diabetes. Studies of the effects of transplantation on diabetes complications are encouraging which, when coupled with improved surgical outcomes, may increase opportunities for transplant. PMID- 1451626 TI - A better method for demonstrating the relationship between factors affecting glycemic control. PMID- 1451627 TI - Preparing for natural disasters: a survival plan for persons with diabetes. PMID- 1451628 TI - Volunteer Protection Act (H.R. 911): protection for AADE volunteers. PMID- 1451629 TI - Photography as a tool in assessment and rapport development in clients with diabetes: research brief. AB - Certainly no major conclusions or generalizations can be made from a pilot study of this size. However, as is the nature of pilot studies, needed modifications in methodology have been discovered. Also, it is obvious that rapport development may be evaluated with the MISS, and the use of a camera has proven to be a worthwhile assessment and intervention tool. The results of this pilot study would certainly warrant continuation with a larger study. Rapport development has not been studied in diabetes. Perhaps rapport may be at risk because of the lengthy provider-patient relationship and the need for repeated physician reinforcement of required medical regimens and some associated life-style changes. In this study, rapport appeared to increase slightly in the experimental (camera) group and decrease in the control (non-camera) group. From the patients' perspective, use of photography communicates that the health care provider cares about them as individuals, is interested in their life-styles, and is seeking methods to best integrate the treatment regimen into their individual life patterns. However, rapport development may deteriorate over time with individuals who have a chronic illness (as indicated by some decrease in pretest/posttest mean differences in both groups), thus emphasizing the responsibility of health care providers to actively work to preserve rapport. The camera may be one method to accomplish this goal. When treating an individual with a chronic illness, health care providers tend to view the patient and problem as one entity rather than as two separate components. The camera may help to enhance this separation and promote understanding of the individual by means of rapport development. PMID- 1451630 TI - [Mathematical model of membrane potential oscillations in bursting neurons of Helix pomatia]. PMID- 1451631 TI - [Formation of the dose burdens on agricultural animals during the accident at the Chernobyl AES and effect of their evacuation on the dose absorbed]. PMID- 1451632 TI - [Growth inhibiting and cytostatic activity of binuclear platinum (II) triamine complexes with polymethylenediamines]. PMID- 1451633 TI - [High molecular weight nuclear matrix phosphoprotein as an analog of the MAP1 protein from brain microtubules associated with DNA in a Mg- dependent manner]. PMID- 1451634 TI - [Decreased MR-activity among chromosomes with a lethal mutation in a Drosophila melanogaster natural population]. PMID- 1451635 TI - [Isotopic effects in biosystems and the problem of aging of the organism]. PMID- 1451636 TI - [Excitonic cleavage--the reason for spectral features of the colchicine-tubulin complex]. PMID- 1451637 TI - [Effect of phorbol esters and amiloride on the radiation-induced interphase death of thymocytes]. PMID- 1451638 TI - [The effect of ftorofok on the enzymatic activity of various isoforms of cytochrome P-450]. PMID- 1451639 TI - [Functional changes in lymphokine-activated lymphocytes depending on the incubation time with interleukin-2]. PMID- 1451640 TI - [Further studies on the removal of (134), (137)Cs from animal meat]. PMID- 1451641 TI - Effects of macrolide antibiotics on gastrointestinal motility in fasting and digestive states. AB - The effect of macrolide antibiotics on gastrointestinal motility was studied in unanaesthetized dogs by using strain-gauge transducers. Midecamycin acetate, leucomycin, josamycin and acetylspiramycin, which are 16-membered macrolides, did not affect the gastrointestinal motility and no symptoms of gastrointestinal disorder were observed. On the other hand, erythromycin, roxithromycin, clarithromycin and oleandomycin, which are 14-membered macrolides, caused giant contraction and disorder symptoms. Moreover, it was found that the glycosidic linkages of the lactone ring were necessary for a structure to exert strong contractile activity. PMID- 1451642 TI - Transfer of beta-lactam preparations created in Japan to lung tissue and the drug selection for chemotherapy of respiratory tract infections. AB - Intraoperative transfer of eight beta-lactam preparations to lung tissues was investigated by one-gram one-hour intravenous drip infusion immediately prior to operation. The Japanese drugs used were piperacillin, cefotiam, ceftizoxime, cefuzonam, latamoxef, flomoxef, cefotetan and cefbuperazone. The serum peak level was highest with cefotetan, 104.1 micrograms/ml, followed by cefbuperazone, latamoxef, ceftizoxime, cefotiam, piperacillin, flomoxef and cefuzonam, in decreasing order. Except for cefuzonam, there was a correlation between the serum peak level and the human serum protein binding rate (r = 0.89). There was a correlation (r = 0.98) between the Cmax of normal lung tissue (alveoli) level and the serum peak level (Cmax), but no correlation between the former and the human serum protein binding rate. The tumour level was lower than that in normal lung tissue (alveoli), but the tissue level at the obstructive pneumonia area was higher. The Cmax of bronchiolar tissue level was highest with cefuzonam, followed by latamoxef. There was no correlation between the Cmax of bronchiolar tissue level and the serum peak level, human serum protein binding rate or the Cmax of lung tissue (alveoli) level. It is therefore presumed that the drug level in tissue of the acute pneumonia area can be determined from the serum peak level of the respective drug. An appropriate drug for chemotherapy may be selected from beta-lactam preparations which are effective against main causative organisms in acute respiratory tract infections. Cefuzonam and latamoxef are especially useful for chemotherapy in patients with acute bronchiolitis. PMID- 1451643 TI - Microbiologic profile of ceftibuten, a new oral cephalosporin. AB - The bactericidal activity of ceftibuten, alone and in combination with other drugs, has been assessed in vitro. The ability to induce a post-antibiotic effect (PAE), the rate of emergence of spontaneous resistant mutants, and the presence of Eagle's phenomenon were also investigated. Ceftibuten rapidly killed most Enterobacteriaceae, Haemophilus, Moraxella and Streptococcus species tested, including beta-lactamase-producing strains with over 90% cfu reduction after only 2 h. Using chequerboard and time-kill tests, ceftibuten was found to react synergistically with aminoglycosides, and to give an indifferent response with ofloxacin against a large number of Gram-negative aerobes and streptococci. Antagonism was never observed. Ceftibuten induced a PAE of approximately 1 h on S. pneumoniae. As expected, no PAE was observed with Gram-negative species. Spontaneous emergence of ceftibuten-resistant strains exposed to supra-MICs of the drug was rare (< or = 10(-8)) in all pathogens tested. No marked Eagle effect was detected when bacteria were treated with ceftibuten at concentrations exceeding 100-fold their MICs. This rules out the possibility that in vivo the high concentrations of ceftibuten reached in the urinary tract may hinder its excellent bactericidal activity. PMID- 1451644 TI - Comparison of norfloxacin and pefloxacin in the prophylaxis of bacterial infection in neutropenic cancer patients. AB - In this study the efficacy of norfloxacin and pefloxacin for the antibacterial prophylaxis of granulocytopenia was compared in cancer patients following cytostatic treatment. A total of 136 patients was randomly selected to receive either norfloxacin or pefloxacin. Nineteen patients remained afebrile in the norfloxacin group compared with thirty one in the pefloxacin group (p = 0.045). Twenty four microbiologically documented infections (twelve with and twelve without bacteraemia) occurred in sixty seven patients taking norfloxacin, and twelve in sixty nine patients taking pefloxacin (five with and seven without bacteraemia) (p = 0.015). Only one infection caused by Gram-negative bacilli was observed in the pefloxacin group compared with seven in the norfloxacin group (p = 0.019). In conclusion, both microbiological and clinical results showed pefloxacin to be a better antibacterial agent than norfloxacin for these patients. PMID- 1451645 TI - Acute systemic and splanchnic haemodynamic effects of L-carnitine in patients with cirrhosis. AB - L-carnitine (L-C) is a naturally occurring substance in mammalian tissues that has recently been proposed as a therapeutic agent in hepatic encephalopathy and liver steatosis. L-C also produces some acute, non-metabolic, haemodynamic effects that have not previously been studied in patients with cirrhosis. Therefore, the authors evaluated the acute effect of i.v. administration of L-C (30 mg/kg) on systemic and splanchnic haemodynamics in ten patients (L-C group) with chronic liver disease (Child-Pugh's class A: 4, B: 3, C: 3 patients) and a control group composed of ten patients with similar clinical characteristics (Child-Pugh's class A: 5, B: 2, C: 3 patients) who received placebo. Heart rate, cardiac index and pulmonary arterial pressure (measured by right heart catheterization) decreased slightly but significantly in the L-C group and the changes observed in stroke volume were highly correlated to the Pugh's score. Moreover, the hepatic venous pressure gradient (measured by hepatic vein catheterization) decreased significantly in the L-C group, whereas no changes occurred in the placebo group. The overall response to L-C was contradictory to that previously observed in animals and humans with normal liver function, and the extent seemed to depend on the severity of liver disease. The effect of the drug on cardiac index, heart rate and hepatic venous gradient could possibly be beneficial for patients with hyperdynamic circulatory condition and portal hypertension. PMID- 1451646 TI - Phase I trial of cystemustine, a new cysteamine (2-chloroethyl) nitrosourea: an intrapatient escalation scheme. AB - A trial of cystemustine, a cysteamine nitrosourea, was carried out on 34 patients with advanced malignancies at increasing dosage of the drug over a period of up to 190 days in seven or eight cycles. A partial response to treatment was obtained in three patients. A degree of haematological toxicity developed in a number of the patients. PMID- 1451647 TI - [The effect of acute cellular rejection on liver function following orthoptic liver transplantation. Quantitative functional studies with the 14C-aminopyrine breath test]. AB - To test the effect of acute cellular rejection on liver function as represented by cytochrome-P-450 enzyme activity, the 14C-aminopyrine breath test (ABT) was performed prospectively in 46 patients (31 men, 15 women; mean age 48 [15-66] years) who had undergone a total of 50 orthotopic liver transplantations. Routine biochemical tests were performed daily until the 30th postoperative day, while the ABT was done daily on days 1-10 and three times weekly on days 11-30, and liver puncture biopsies were obtained once weekly or more often if there was clinical suspicion of rejection. Histologically confirmed cellular rejection occurred within the stated period of observation in eight patients (five women, three men; median age 45 [18-59] years). Results of routine laboratory tests (transaminases, bilirubin, thromboplastin time), as well as bile-flow and body temperature, did not vary uniformly. On the other hand, results of ABT at the time of rejection showed a decrease in all patients by an average of 65% (P < 0.01). Changes in the ABT preceded those in other tests by 1-2 days in four patients, being the only measurable functional abnormality in one. All rejection episodes responded to glucocorticoid pulse-treatment (three times 1 g methyl prednisolone). Using ABT results as criterion, liver function became normal after the glucocorticoid injection within 4-11 days. These data indicate that the ABT is suitable in the routine monitoring of transplant function, thus facilitating early diagnosis and controlled treatment of acute cellular rejection. PMID- 1451648 TI - [Intra-arterial calcium provocation for the preoperative diagnosis of the location of an occult insulinoma]. AB - Blood-sugar levels below 40 mg/dl were measured during syncope in two female patients (aged 59 and 73 years). Suspected organic hyperinsulinism was confirmed by a fasting test. Ultrasound examination and computed tomography failed to demonstrate an insulinoma. Coeliacomesentericography was then undertaken together with a selective intra-arterial calcium provocation test of the pancreas (0.4 or 0.5 mmol calcium in physiological saline was injected into the pancreas-supplying arteries--proximal and distal splenic, superior mesenteric and gastroduodenal). The insulin level was determined in simultaneously obtained hepatic venous blood. In case 1, the insulin level rose tenfold after calcium injection into the proximal splenic artery, indicating a process in the body of the pancreas. In case 2, a steep rise in insulin occurred after injection into the truncus coeliacus and the proximal and distal splenic artery, suggesting an insulinoma in the tail of the pancreas. The site of the insulinoma was confirmed in both cases at surgery. The adenoma was enucleated in case 1, removed by partial resection of the tail of the pancreas in case 2.--These observations show that occult insulinomas can be localized preoperatively by intraarterial calcium injection with measurement of insulin concentration in simultaneously obtained hepatic venous blood. PMID- 1451649 TI - [The therapy of the heparin-induced thrombosis-thrombocytopenia syndrome with immunoglobulins]. AB - A 51-year-old obese woman who had just undergone a second osteotomy for arthrosis of the hip joint was given unfractionated heparin, 7,500 IU subcutaneously three times daily, as thrombosis prophylaxis. Signs of fulminant pulmonary embolism occurred on the 16th postoperative day with a platelet count of 33,000/microliters. Suspected heparin-induced thrombocytopenia and thrombosis (HITT) was confirmed by platelet tests. When heparin had been discontinued immunoglobulin G was administered, seven times 5 g intravenously, in view of the immunological genesis of HITT. In addition thrombolysis treatment with streptokinase combined with phenprocoumon was undertaken, until satisfactory anticoagulation was achieved after 4 days. Platelet count rose to 136,000/microliters within 20 hours of the first immunoglobulin dose. Complete clinical normality was restored, scintigraphy showed no perfusion deficit in the lungs. PMID- 1451650 TI - [The diagnostic significance of lipoprotein(a)]. PMID- 1451651 TI - [Angiotensin-converting enzyme inhibition and angina pectoris]. PMID- 1451652 TI - [Quality assurance in publications]. PMID- 1451653 TI - [The indications for acetazolamide]. PMID- 1451654 TI - [Physical activity and type-II diabetes mellitus]. PMID- 1451655 TI - Imprinting of phosphoribosyltransferases during preimplantation development of the mouse mutant, Hprtb-m3. AB - The measurement of the activity of the X-linked enzyme HPRT has been widely used as an indicator of X-chromosome activity during preimplantation development in the mouse. More recently, the concomitant measurement of the activity of the autosomally-encoded enzyme APRT has been used in an attempt to decrease the variability inherent in the measurement of enzyme activity from minute samples such as preimplantation embryos. In this study the use of the HPRT-deficient mouse mutant, Hprtb-m3, allowed the unequivocal identification of the parental origin of HPRT activity measured in embryos derived from crosses between wild type mice, and mice which were homozygous or hemizygous for the Hprtb-m3 allele. Results were similar to those of a previous study, where oocyte-encoded HPRT activity accounted for about 10% of total HPRT activity at 76 hours post human chorionic gonadotrophin injection and the paternally-derived Hprt allele was shown to be transcriptionally active by the late 2-cell stage. In contrast to other studies, differential expression of the two Hprt alleles was detected during the preimplantation period, in embryos derived from crosses between wild type and HPRT-deficient mice. Evidence was also found for the existence of an X linked locus which influences the amount of APRT activity in the unfertilized oocyte. We propose that the expression pattern of this locus may be influenced by its parental origin. PMID- 1451656 TI - Platelet-derived growth factor-A and its receptor are expressed in separate, but adjacent cell layers of the mouse embryo. AB - The localized developmental expression of murine platelet-derived growth factor A (PDGF-A) was compared to that of its receptor (Pdgfra). Our in situ hybridization study included germ layers of primitive streak embryos, early axial structures (dermatome, myotome, sclerotome, floor plate), the skin and some of its derivatives (hair and mammary gland), the developing forelimb, the branchial arches and various sense organs (otic vesicle, olfactory epithelium and the eye). We report that PDGF-A and Pdgfra are expressed in separate, but adjacent cell layers in these structures and that in most, the ligand is expressed in the epithelium, whereas the receptor in the mesenchyme. This localization corresponds to classical experimental evidence for developmental interactions across cell layers. We suggest that the spatio-temporal regulation of PDGF-A and Pdgfra, and other related systems, represents one model for the spatial regulation of receptor-ligand interactions. PMID- 1451657 TI - BHK-21-derived cell lines that produce basic fibroblast growth factor, but not parental BHK-21 cells, initiate neuronal differentiation of neural crest progenitors. AB - We present evidence that basic fibroblast growth factor (bFGF)-producing cells stimulate primary differentiation of neurons from neural crest progenitors. Baby hamster kidney (BHK-21) cells were stably cotransfected with plasmid pSV2/neo, which contains the gene conferring resistance to the neomycin analog G418 and expression vectors containing the human bFGF cDNA. Various clones, which differed in their bFGF production levels, were isolated. Homogeneous neural crest cells were cultured on monolayers of bFGF-producing, BHK-21-derived cell lines. While the parental BHK-21 cells, which do not produce detectable bFGF, had poor neurogenic ability, the various bFGF-producing clones promoted a 1.5- to 4-fold increase in neuronal cell number compared to the parental cells. This increase was correlated with the levels of bFGF produced by the different transfected clones, which ranged between 2.3 and 140 ng/mg protein. In contrast, no stimulation of neuronal differentiation was observed when neural crest cells were grown on monolayers of parental BHK cells transfected with plasmid pSV2/neo alone, or on a parental BHK-derived clone, which secretes high amounts of recombinant vascular endothelial growth factor (VEGF). Furthermore, the neuron promoting ability of bFGF-producing cells could be mimicked by addition of exogenous bFGF to neural crest cells grown on the parental BHK line. A similar treatment of neural crest cells grown on laminin substrata, instead of BHK cells, resulted in increased survival of non-neuronal cells, but not of neurons (see also Kalcheim, C. 1989, Dev. Biol. 134, 1-10). Taken together, these results suggest that bFGF stimulates neuronal differentiation of neural crest cells by a cell-mediated signalling mechanism. PMID- 1451658 TI - Development of left/right handedness in the chick heart. AB - The chick heart tube develops from the fusion of the right and left areas of precardiac mesoderm and in almost all cases loops to the embryo's right-hand side. We have investigated whether any intrinsic difference exists in the right and left areas of precardiac mesoderm, that influences the direction of looping of the heart tube. Chick embryos incubated to stages 4,5 and 6 were cultured by the New method. Areas of precardiac mesoderm were exchanged between donor and host embryos of the same stage and different stages to form control, double-right and double-left sided embryos. Overall, double-right sided embryos formed many more left-hand loops than double-left sided embryos. At stages 4 and 5 a small percentage of double-right embryos formed left-hand loops (13%) whereas at stage 6 almost 50% of hearts had left-hand loops. Control embryos formed right-hand loops in 97% of cases. The stability of right-hand heart looping by double-left sided embryos, may be related to the process of 'conversion', whereas the direction of looping by double-right sided embryos has become randomised. There is some indication that an intrinsic change occurred in the precardiac mesoderm between stages 5 and 6 that later influenced the direction of looping of the heart tube. The direction of body turning is suggested to be linked to the direction of heart looping. PMID- 1451659 TI - Inhibin alpha- and beta A-subunit immunoreactivity in the chicken embryo during morphogenesis. AB - Antibodies against synthetic peptides selected from the amino acid sequences of human inhibin alpha- and beta A-subunits were used to examine the distribution of inhibin subunit immunoreactivity in chicken embryos during the first week of development. Inhibin alpha-subunit immunoreactivity was localized in skeletal and smooth muscle myoblasts as well as developing cardiac muscle cells. In somites, immunostaining was seen exclusively in myotomes. The appearance of alpha-subunit immunoreactivity was correlated with myogenic differentiation; immunoreactivity was not seen in non-differentiated mesenchymal cells or in terminally differentiated adult muscle cells. In cardiac muscle, some immunopositive myocytes were seen also in the adult. In the adult heart, the Purkinje fibers were strongly immunoreactive, suggesting a possible role of the immunoreactive protein in the impulse-conducting function of these specialized cells. Inhibin alpha-subunit immunoreactivity was also seen in the visceral and parietal cells of the Bowman's capsule in both mesonephric and metanephric kidneys. In addition to mesodermal derivatives, alpha-subunit immunoreactivity was localized in neuroepithelial cells and axons in the developing central nervous system. Immunoblotting with anti-alpha(1-32) revealed two protein bands with M(r) values of 50,000 and 32,000 in cytosol samples of whole embryos under nonreducing conditions. In reduced samples an approximately 14,000 M(r) protein species was detected. Inhibin beta A-subunit immunoreactivity was detected only in chondrocytes, suggesting that the immunoreactive protein might represent a chicken homologue of the various cartilage and bone morphogenetic proteins expressed in mammals. PMID- 1451660 TI - Induction of follicle formation and hair growth by vibrissa dermal papillae implanted into rat ear wounds: vibrissa-type fibres are specified. AB - Adult vibrissa follicle dermal papillae have the capacity to induce hair growth and follicle formation when associated with epidermis from various sources. However, the range of conditions under which hair follicle induction will take place has not been established. The question of whether or not the adult papilla carries information to impose fibre-type specificity has also not been fully answered. This study describes how the implantation of isolated papillae into small incisional cuts on the rat ear pinna resulted in the subsequent emergence of abnormally large hair fibres from the wound sites. Many of these hairs were found to display vibrissa-type characteristics. Histological observations indicated that the papillae had interacted with the edges of the wound epidermis to produce new, and particularly large follicles, while immunohistochemical staining revealed that early follicle construction was accompanied by a profusion of the basement membrane constituents laminin and type IV collagen in the subjacent dermis. These findings show that adult rat papillae retain the capacity, as displayed by embryonic dermis, to determine vibrissa specificity in induced follicles. PMID- 1451661 TI - Developmental modulation of myosin expression by thyroid hormone in avian skeletal muscle. AB - It is well established that a rise in circulating thyroid hormone during the second half of chick embryo development significantly influences muscle weight gain and bone growth. We studied thyroid influence on differentiation in slow anterior latissimus dorsi (ALD) and fast posterior latissimus dorsi (PLD) muscles of embryos rendered hypothyroid by hypophysectomy or administration of an anti thyroid drug. The expression of native myosins and myosin light chains (MLCs) was studied by electrophoretic analysis, and the myosin heavy chain (MHC) was characterized by immunohistochemistry. The first effects of hypothyroid status were observed at day 21 of embryonic development (stage 46 according to Hamburger and Hamilton). Analysis of myosin isoform expression in PLD muscles of hypothyroid embryos showed persistence of slow migrating native myosins and slow MLCs as well as inhibition of neonatal fast MHC expression, indicating retarded differentiation of this muscle. In ALD muscle, hypothyroidism maintained fast embryonic MHC and induced noticeable amounts of fast MLCs, thus delaying slow muscle differentiation. Our results suggest that thyroid hormones play a role in modulating the appearance of neonatal fast MHC and the disappearance of isomyosins transiently present during embryogenesis. However, T3 supplemental treatment would seem to compensate in part for the effects of hypothyroidism induced by hypophysectomy, suggesting that thyroid hormone might interfere with other factors also accounting for the observed effects. PMID- 1451662 TI - The developmental switch in embryonic rho-globin expression is correlated with erythroid lineage-specific differences in transcription factor levels. AB - During chicken embryogenesis, the rho-globin gene is expressed only in the early developmental stages. We have examined the mechanisms that are responsible for this behavior. The transcription of the rho-globin gene is strongly correlated with the presence during development of primitive erythroid lineage cells, consistent with the idea that the expression of the rho-globin gene is restricted to that lineage. The "switching off" of rho-globin during development thus reflects the change from primitive to definitive cell lineages which occurs during erythropoiesis in chicken. We use transient expression assays in primary erythroid and other cells to show that the information for lineage- and tissue specific expression of the rho-globin gene is contained in a 456 bp region upstream of the gene's translational start site. DNA-binding studies, coupled with analysis of the effect on expression of deletions and binding site mutations, were used to identify important control elements within this 456 bp region. We find that binding sites for the ubiquitous transcription factor Sp1, and the specific hematopoietic factor GATA-1, are crucial for expression of the gene in primitive erythroid cells. Quantitative analysis shows that nuclei of the primitive erythroid lineage contain 10-fold more of these factors than do the nuclei of definitive cells. We show that in principle these differences in factor concentration are sufficient to explain the lineage-specific behavior that we observe in our assays. We suggest that this may be an important part of the mechanism for lineage-restricted rho-globin expression during chicken erythroid development. Similar mechanisms may be involved in regulation of other (but not all) members of the globin family. PMID- 1451663 TI - Ventrolateral regionalization of Xenopus laevis mesoderm is characterized by the expression of alpha-smooth muscle actin. AB - Mesodermal patterning in the amphibian embryo has been extensively studied in its dorsal aspects, whereas little is known regarding its ventrolateral regionalization due to a lack of specific molecular markers for derivatives of this type of mesoderm. Since smooth muscles (SM) are thought to arise from lateral plate mesoderm, we have analyzed the expression of an alpha-actin isoform specific for SM with regard to mesoderm patterning. Using an antibody directed against alpha-SM actin that recognized specifically this actin isoform in Xenopus, we have found that the expression of alpha-SM actin is restricted to visceral and vascular SM with a transient expression in the heart. The overall expression of the alpha-SM actin appears restricted to the ventral aspects of the differentiating embryo. alpha-SM actin expression appears to be activated following mesoderm induction in animal cap derivatives. Moreover, at the gastrula stage, SM precursor cells are regionalized since they will only differentiate from ventrolateral marginal zone explants. Using the animal cap assay, we have found that alpha-SM actin expression is specifically induced in treated animal cap with bFGF or a low concentration of XTC-MIF, which induce ventral structures, but not with a high concentration of XTC-MIF, which induces dorsal structures. Altogether, these results establish that alpha-SM actin is a reliable marker for ventrolateral mesoderm. We discuss the importance of this novel marker in studying mesoderm regionalization. PMID- 1451664 TI - Spatial and developmental changes in the respiratory activity of mitochondria in early Drosophila embryos. AB - Mitochondria of early Drosophila embryos were observed with a transmission electron microscope and a fluorescent microscope after vital staining with rhodamine 123, which accumulates only in active mitochondria. Rhodamine 123 accumulated particularly in the posterior pole region in early cleavage embryos, whereas the spatial distribution of mitochondria in an embryo was uniform throughout cleavage stages. In late cleavage stages, the dye showed very weak and uniform accumulation in all regions of periplasm. Polar plasm, sequestered in pole cells, restored the ability to accumulate the dye. Therefore, it is concluded that the respiratory activity of mitochondria is higher in the polar plasm than in the other regions of periplasm in early embryos, and this changes during development. The temporal changes in rhodamine 123-staining of polar plasm were not affected by u.v. irradiation at the posterior of early cleavage embryos at a sufficient dosage to prevent pole cell formation. This suggests that the inhibition of pole cell formation by u.v. irradiation is not due to the inactivation of the respiratory activities of mitochondria. In addition, we found that the anterior of Bicaudal-D mutant embryos at cleavage stage was stained with rhodamine 123 with the same intensity as the posterior of wild-type embryos. No pole cells form in the anterior of Bic-D embryos, where no restoration of mitochondrial activity occurs in the blastoderm stage. The posterior group mutations that we tested (staufen, oskar, tudor, nanos) and the terminal mutation (torso) did not alter staining pattern of the posterior with rhodamine 123. PMID- 1451665 TI - The generation of cell diversity during early neurogenesis in Drosophila. PMID- 1451666 TI - Generation and early differentiation of glial cells in the first optic ganglion of Drosophila melanogaster. AB - We have examined the generation and development of glial cells in the first optic ganglion, the lamina, of Drosophila melanogaster. Previous work has shown that the growth of retinal axons into the developing optic lobes induces the terminal cell divisions that generate the lamina monopolar neurons. We investigated whether photoreceptor ingrowth also influences the development of lamina glial cells, using P element enhancer trap lines, genetic mosaics and birthdating analysis. Enhancer trap lines that mark the differentiating lamina glial cells were found to require retinal innervation for expression. In mutants with only a few photoreceptors, only the few glial cells near ingrowing axons expressed the marker. Genetic mosaic analysis indicates that the lamina neurons and glial cells are readily separable, suggesting that these are derived from distinct lineages. Additionally, BrdU pulse-chase experiments showed that the cell divisions that produce lamina glia, unlike those producing lamina neurons, are not spatially or temporally correlated with the retinal axon ingrowth. Finally, in mutants lacking photoreceptors, cell divisions in the glial lineage appeared normal. We conclude that the lamina glial cells derive from a lineage that is distinct from that of the L-neurons, that glia are generated independently of photoreceptor input, and that completion of the terminal glial differentiation program depends, directly or indirectly, on an inductive signal from photoreceptor axons. PMID- 1451667 TI - The involvement of the Notch locus in Drosophila oogenesis. AB - The Notch gene in Drosophila encodes a transmembrane protein with homology to EGF that, in a variety of tissues, appears to mediate cell interactions necessary for cell fate choices. Here we demonstrate that oogenesis and spermatogenesis depend on Notch. We examine the phenotypes of the temperature-sensitive Notch allele, Nts1, and, using a monoclonal antibody, determine the cellular and subcellular distribution of Notch protein during oogenesis. We show that Nts1 is associated with a missense mutation in the extracellular, EGF homologous region of Notch and that at non-permissive temperatures oogenesis is blocked and the subcellular distribution of the protein is altered. In wild-type ovaries, Notch protein is found on the apical surface of somatically derived follicle cells, while in the germline-derived cells the protein is not polarized. These findings are discussed in view of the hypothesis that Notch acts as a multifunctional receptor to mediate developmentally important cell interactions. PMID- 1451668 TI - Reorganization of the cytoskeleton during Drosophila oogenesis: implications for axis specification and intercellular transport. AB - Inhibitor studies have implicated microtubules in at least three important developmental processes during Drosophila oogenesis: oocyte determination and growth during stages 1 through 6, positioning of the anterior determinant bicoid mRNA during stages 9 through 12, and ooplasmic streaming during stages 10b through 12. We have used fluorescence cytochemistry together with laser scanning confocal microscopy to identify distinct microtubule structures at each of the above three periods that are likely to be involved in these processes. During stages 1 through 7, maternal components synthesized in nurse cells are transported through cytoplasmic bridges to the oocyte. At this time, microtubules that appear to originate in the oocyte pass through these cytoplasmic bridges into the adjacent nurse cells; these microtubules are likely to serve as a polarized scaffold on which maternal RNAs and proteins are transported. During stages 7 and 8, microtubules in the oocyte cortex reorganize to form an anterior to-posterior gradient, suggesting a role for microtubules in the localization of morphogenetic determinants. Finally, when ooplasmic streaming begins during stage 10 b, it is accompanied by the assembly of subsurface microtubule arrays that spiral around the oocyte; these arrays disassemble as the oocyte matures and streaming stops. During ooplasmic streaming, many vesicles are closely associated with the subsurface microtubules, suggesting that streaming is driven by vesicle translocation along microtubules. We believe that actin plays a secondary role in each of these morphogenetic events, based on our parallel studies of actin organization during each of the above stages of oogenesis. PMID- 1451669 TI - A comparison of intracellular changes in porcine eggs after fertilization and electroactivation. AB - The experiments compare intracellular changes in porcine eggs induced by electrical activation with those induced by sperm penetration. Adequate electrostimulation induces changes in both cortical granule exocytosis and protein synthesis similar to those induced by sperm during fertilization. However, ionic changes induced by electrostimulation differ markedly from those initiated at fertilization. Thus, dynamic video imaging using Fura-2 as a Ca2+ probe provides evidence that parthenogenetic activation induced by electrostimulation is initiated by a single sharp rise in the concentration of intracellular free calcium ([Ca2+]i) in the egg. The intracellular Ca2+ transient increase is triggered by an influx of extracellular Ca2+ immediately after electrostimulation. The amplitude of the intracellular Ca2+ transient increase is a function both of the extracellular Ca2+ concentration and of electric field parameters (field strength and pulse duration). Imaging demonstrates further that a single electrical pulse can only induce a single Ca2+ transient which usually lasts three to five minutes; no further Ca2+ transients are observed unless additional electrical stimuli are applied. By contrast, sperm-induced activation is characterised by a series of Ca2+ spikes which continue for at least 3 hours after sperm-egg fusion. The pattern of Ca2+ spiking after fertilization is not consistent during this period but changes both in frequency and amplitude. Overall, the results demonstrate that, although electrostimulation induces both cortical granule exocytosis and protein reprogramming in porcine eggs, it does not reproduce the pattern of [Ca2+]i changes induced by sperm entry at fertilization. PMID- 1451670 TI - 3' non-translated sequences in Drosophila cyclin B transcripts direct posterior pole accumulation late in oogenesis and peri-nuclear association in syncytial embryos. AB - We have characterised forms of the Drosophila cyclin B transcript that differ as a result of a splicing event which removes a nucleotide segment from the 3' untranslated region. In oogenesis, both cyclin A RNA and a shorter form of the cyclin B transcript are seen in the cells of the germarium that are undergoing mitosis. The shorter cyclin B transcript alone is then detectable in the presumptive oocyte until stages 7-8 of oogenesis. Both cyclin A RNA and a longer form of the cyclin B RNA are then synthesised in the nurse cells during stages 9 11, to be deposited in the oocyte during stages 11-12. These transcripts become evenly distributed throughout the oocyte cytoplasm but, in addition, those of cyclin B become concentrated at the posterior pole. Examination of the distributions of RNAs transcribed from chimeric cyclin genes indicates that sequences in the 3' untranslated region of the larger cyclin B RNA are required both for it to become concentrated at the posterior pole and to direct those transcripts in the body of the syncytial embryo to their peri-nuclear localisation. These sequences are disrupted by the splicing event which generates smaller cyclin B transcripts. PMID- 1451671 TI - Pleomorphic adenoma: a preliminary histopathologic comparison between tumors occurring in the deep and superficial lobes of the parotid gland. AB - Twenty-four cases of pleomorphic adenoma of the parotid gland were retrospectively reviewed. The histopathological features of capsular thickness, penetration and completeness, tumoral cell population and mitotic activity were analyzed in twelve superficial lobe and twelve deep lobe tumors. The capsules were found to be significantly thicker and less likely to be penetrated by tumor in the deep lobe group. No significant differences in completeness of encapsulation, cell population or mitotic activity were found between the two groups. This may explain the clinical suggestion that the less aggressive surgical approach which is often performed does not compromise the prognosis for recurrence in the deep lobe lesions. PMID- 1451672 TI - Sinusitis--inspecting the causes and treatment. AB - In summary, sinusitis is a common disease caused by viruses, bacteria and the accumulation of excessive secretions and inflammatory mediators that impair the function of the mucociliary transport. Combination treatment is usually necessary to treat the cause and relieve the symptoms of sinusitis. Therapy aims at eliminating causative bacteria with antibiotics, decongesting edematous membranes, and thinning mucus with use of a mucolytic-expectorant. Improving the rheology of mucus by thinning abnormally thickened secretions may improve mucociliary transport and enhance penetration of antibiotics. Acute sinusitis usually responds to treatment within 2 weeks. However, if treatment is unsuccessful or a severe complication occurs, intravenous antibiotics may be necessary along with antral puncture and lavage. In resistant cases, an appropriate surgical procedure may enhance the drainage. PMID- 1451673 TI - Inverted papilloma of the nose and paranasal sinuses in children. AB - Inverted papillomas are rare nasal and sinus neoplasms in children. The disturbing biological characteristics of these tumors seen in adults, including malignant degeneration and the high frequency of recurrence, have been similarly observed in the pediatric population. Therefore, inverted papilloma in children mandates similar treatment to that proven effective in adults, including wide excision and careful histopathological examination of any tissue excised. Radiation therapy should be reserved for those tumors associated with carcinoma. Since recurrences can occur after long periods of time, life-long follow-up is warranted. PMID- 1451674 TI - Postcricoid surface laryngeal electrode. AB - Progress in identification of the recurrent laryngeal nerve in thyroid and parathyroid surgery has lagged behind the identification of other head and neck nerves. Attempts to use electronic pulsed nerve stimulators with evoked response electromyography have failed due to the absence of a convenient and effective method of monitoring the larynx. A Postcricoid Laryngeal Surface Electrode as herein described shows excellent initial results as an electrode for electromyographic monitoring of the larynx for recurrent laryngeal nerve identification. PMID- 1451675 TI - Auditory brainstem evoked response in patients undergoing carotid endarterectomy. AB - Auditory brainstem evoked response-(ABR) may be affected by changes in cerebral blood flow. Apart from its primary indications for prevention of stroke and transient ischemic attacks-(TIA's), internal carotid endarterectomy-(ICE) has been shown to improve cognitive function and cause diminution of tinnitus and vertigo. A one-week postoperative ABR previous study of patients undergoing ICE demonstrated no change in ABR recordings. In order to evaluate possible late changes, we have conducted a prospective study of the delayed effects of ICE on ABR in 13 patients. No initial pathology was noted and no significant change found in any of the absolute and interpeak latencies of ABR waves. PMID- 1451676 TI - Extrusion rate of Shah and Shepard ventilation tubes in children. AB - Shah and Shepard ventilation tubes are the two most commonly used ventilation tube in current practice. In some centres these two tubes are used interchangeably, in others the Shepard is often used as the first 'grommet' of insertion and the Shah for subsequent insertions. A study was undertaken of extrusion rate of these ventilation tubes in 180 children who had surgery for Serous otitis media in 1987. Extrusion time was found to be very significantly different between these tubes. The Shah ventilation tube remains in situ 3 months longer than the Shepard. A case is made for the use of Shah ventilation tubes as the first "grommet" of insertion. Otorrhoea following insertion of ventilation tube did not affect the extrusion rate of ventilation tubes in this study. Nor has otorrhoea a predilection for any particular ventilation tube. PMID- 1451677 TI - Reflux laryngopharyngitis. PMID- 1451678 TI - Antibiotics and chronic otitis media. PMID- 1451679 TI - A single-fluor approach to DNA sequence determination using high performance capillary electrophoresis. AB - The Tabor and Richardson strategy for enzymatic chain termination sequencing of DNA using relative peak intensity has been adapted to high performance capillary gel electrophoresis with laser induced fluorescence detection. This approach to DNA sequencing involves the use of only a single fluor and results in significant reduction in the time required to determine a DNA sequence without the use of highly complicated and expensive instrumentation. We present a modification of the Tabor and Richardson approach employing two reactions, each containing complementary mixtures of only three ddNTP's in the concentration ratio 4:2:1. The DNA sequence is determined by relative peak height and by assigning the missing ddNTP to "gaps" between the peaks. The use of only three terminators/reaction simplifies the software task of differentiating between the termination types and makes more efficient use of the available dynamic range. Both complementary mixes generate complete sequence information and the two data files are combined in order to make a more confident sequence call. This process helps to eliminate errors caused by occasional non-uniform incorporation of ddNTP's or false terminations and also alleviates some of the difficulty associated with reading through compressed regions of the electropherogram. PMID- 1451680 TI - Stability of capillary gels for automated sequencing of DNA. AB - Recent interest in capillary gel electrophoresis has been fueled by the Human Genome Project and other large-scale sequencing projects. Advances in gel polymerization techniques and detector design have enabled sequencing of DNA directly in capillaries. Efforts to exploit this technology have been hampered by problems with the reproducibility and stability of gels. Gel instability manifests itself during electrophoresis as a decrease in the current passing through the capillary under a constant voltage. Upon subsequent microscopic examination, bubbles are often visible at or near the injection (cathodic) end of the capillary gel. Gels have been prepared with the polyacrylamide matrix covalently attached to the silica walls of the capillary. These gels, although more stable, still suffer from problems with bubbles. The use of actual DNA sequencing samples also adversely affects gel stability. We examined the mechanisms underlying these disruptive processes by employing polyacrylamide gel filled capillaries in which the gel was not attached to the capillary wall. Three sources of gel instability were identified. Bubbles occurring in the absence of sample introduction were attributed to electroosmotic force; replacing the denaturant urea with formamide was shown to reduce the frequency of these bubbles. The slow, steady decline in current through capillary sequencing gels interferes with the ability to detect other gel problems. This phenomenon was shown to be a result of ionic depletion at the gel-liquid interface. The decline was ameliorated by adding denaturant and acrylamide monomers to the buffer reservoirs. Sample-induced problems were shown to be due to the presence of template DNA; elimination of the template allowed sample loading to occur without complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451681 TI - Formamide modified polyacrylamide gels for DNA sequencing by capillary gel electrophoresis. AB - Compressions are occasionally found during the separation of DNA sequencing fragments, particularly in G/C-rich regions and in gels operated at room temperature. Addition of at least 10% formamide to urea/polyacrylamide sequencing gels improves the denaturing capacity of the gel, minimizing compressions. Addition of 20% or more formamide decreases the separation rate, theoretical plate count, and resolution for normally migrating fragments. An optimum concentration of 10% formamide improves resolution of compressed regions without degrading the other characteristics of the gel. Operation of gels at room temperature simplifies the engineering associated with automated sequencers based on capillary gel electrophoresis. PMID- 1451682 TI - Continuous, on-line DNA sequencing using a versatile infrared laser scanner/electrophoresis apparatus. AB - A new apparatus for continuously detecting fluorescently labeled DNA fragments is based on infrared fluorescence technology. This technology combines state-of-the art developments in chemistry, laser technology, and detection, while achieving improved reliability, sensitivity, and flexibility for applications including DNA sequencing. DNA molecules labeled with a novel infrared fluorophore are detected during electrophoresis using a scanning infrared fluorescence microscope. The microscope consists of a laser diode for exciting the fluorophore and a silicon avalanche photodiode for detecting the infrared emission. Optimum conditions for detection and throughput are obtained by adjusting electrophoresis, scanning and imaging parameters. Typical DNA sequencing runs (test templates) allow identification of over 500 bases per sample with greater than 99% accuracy. PMID- 1451683 TI - High resolution-separation of DNA bands by electrophoresis with a long gel in a fluorescence-detection DNA sequencer. AB - A high-resolution separation of DNA bands is achieved by electrophoresis with a long gel in DNA base sequencing using fluorescence detection. We separate 760 and 761 base DNA fragments using the 93 cm migration electrophoresis optimized for the separation of DNA bands. A T7 DNA polymerase and an Mn++ buffer are used in sequencing reactions to obtain fluorescence peaks of uniform strength, and the peak areas in the spectrum are used for recognizing the peak number in a cluster of successive peaks. This method is successfully applied to the DNA fragment spectrum obtained by 93 cm migration electrophoresis, which results in a single band differentiation of bands of 1040 base DNA. PMID- 1451684 TI - Compensation for mobility inequalities between lanes computed from band signals in on-line fluorescence DNA sequencing. AB - Among on-line fluorescence DNA sequencing systems, the four-lane method exhibits the potential for reporting an erroneous sequence due to nonuniform mobility of the DNA fragments migrating among the four lanes. This error is manifest in phenomenon commonly called smiling. This paper presents a computational algorithm which compensates for the mobility inequalities between lanes using signal data obtained from the shorter DNA fragments forming the faster migrating bands. The program mainly consists of two routines: (i) calculation of calibration coefficients (mobility ratios between lanes), and (ii) examination of the coefficients by applying them to a later domain of the same signals. Both routines are connected with several feed-back branches for recalculation. Homology analysis of final sequences has shown that the accuracy rate is maximized with this algorithm and any ambiguous result can be assigned to the residual error inherent in the band identification method used. PMID- 1451685 TI - cDNA sequence of three cysteine-rich clusters in the iron-sulfur subunit of complex II (succinate-ubiquinone oxidoreductase) from Caenorhabditis elegans determined by automated DNA sequencer. AB - Homology probing by using mixed primers for polymerase chain reaction (PCR) and a subsequent sequence analysis by automated DNA sequencer were applied to determine a partial cDNA sequence of the iron-sulfur subunit of complex II (succinate ubiquinone oxidoreductase). Complex II is a membrane-bound flavoenzyme, which catalyzes the oxidation of succinate to fumarate in the tricarboxylic acid cycle, and it is a component of the mitochondrial and bacterial respiratory chains. In this study, the partial amino acid sequence of iron-sulfur subunits in Caenorhabditis elegans mitochondria was deduced from the DNA sequence obtained from cDNA-PCR. Mixed oligonucleotide primers corresponding to two conserved regions which appear to be the binding site for the prosthetic group were used. The product of PCR was cloned into plasmid vector pUC 119 and the sequence was determined from double strand plasmid DNA by the dideoxy method using of one-dye, four-lane type the automated DNA sequencer (DSQ-1, Shimadzu). The PCR product contained 483 nucleotides and its deduced amino acid sequence was highly homologous with that in human liver (68.9%) and that of Escherichia coli sdh B product (50.3%). As expected, striking sequence conservation was found around the three cysteine-rich clusters which have been thought to comprise the iron-sulfur centers of the enzyme. PMID- 1451686 TI - Microelectrophoresis for the separation of DNA fragments. AB - A methodology has been developed which significantly reduces the linear dimension necessary for the electrophoretic separation of DNA fragments and oligonucleotides. DNA fragments are rapidly separated into compact, resolvable microscopic banding patterns which can be detected using a high-resolution electronic imaging system. Separations can be carried out in either capillary tube or thin-layer (slab) microgel formats of one centimeter or less in length. The complete separation of all eleven fragments (1353 to 72 base pairs) of the pi X174 DNA/HaeIII restriction ladder was achieved in a total running distance of less than 2 mm and in less than 2 min. The observed band widths for the larger fragments (1353-603 bp) ranged from 18 to 25 microns, with the intermediate and smaller fragments (310 to 72 bp) ranging from 30 microns to 60 microns. The ethidium bromide-stained microgels were analyzed using an epifluorescent microscope combined with an intensified charged coupled device imaging system. In other experiments, single-base resolution of fluoresceinated oligonucleotides in the 20-30 nucleotide range was demonstrated. DNA sequencing may be possible with further optimization. This new methodology departs from the conventional gel formulations and electrophoretic procedures used for the separation DNA fragments. High voltage gradients and the use of highly concentrated and crosslinked homogeneous polyacrylamide gels effects the rapid separation of DNA fragments in very short distances. Analysis of the microgels with proteins of known size (Stokes radius) indicates that separations are occurring in gels with pore sizes close to the diameter of double-stranded DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451687 TI - Electrophoresis and detection of tin-labeled DNAs on open-faced gels. AB - Alternative protocols are necessary for the use of polyacrylamide gel electrophoresis in genome scale sequencing and mapping studies. The use of radioisotopes and manual gel reading will have to be replaced with a flexible labeling system that can be detected at levels similar or to better than radioisotopes but allows automated, high-speed detection. Labeling with stable isotopes is such an alternative. These nondecaying isotopes have the potential to be detected in sub-attomole quantities, despite being surrounded by the gel matrix, due to the high selectivity and sensitivity of resonance-ionization spectroscopy coupled with a mass spectrometer. In this study the detection limits of sputter-initiated resonance ionization spectroscopy (SIRIS) are investigated using thin, open-faced polyacrylamide gels supported by plastic. This system allows reproducibility and flexibility in the choice of gel size and buffer system since the gel can be cast, washed free of polymerization by-products, dried, and stored until use. Various concentrations of an Sn-labeled oligomer were run on these gels and loads of 5 femtomoles/mm could be detected on a 240 microns thick gel. Gels as thin as 60 microns lower the detectable concentration loads to 1 femtomole/mm. The limiting factor is tin contamination in the gel which, if reduced, will further increase detection. Polymerase chain reaction (PCR) products can also be labeled and detected using Sn isotopes, which could prove useful in mapping studies. Also presented are techniques which will facilitate resolution of these PCR products on open-faced gels by employing discontinuous buffers systems and DNA mobility modifiers. PMID- 1451688 TI - Pulsed field sequencing gel electrophoresis. AB - The effect of pulsed fields on sequencing gel electrophoresis is investigated, using DNA fragment markers ranging in size from 20 to 6557 bases. For high continuous electric fields (5000 V/55 cm) band inversion is observed in which fragments larger than 4000 bases migrate faster than those of 800-1000 bases. The use of one-dimensional pulsed field gel electrophoresis (ODPFGE) eliminates band inversion and extends the monotonic size-mobility relationship of the DNA markers up to about 4000 bases. The relevance of these results, obtained using a manual sequencing process with autoradiographic detection, to automated sequences is discussed. PMID- 1451689 TI - Movement of fluorescence pattern after photobleaching: an accelerated procedure for DNA electrophoretic mobility analysis. AB - A new approach which is compatible with many of the existing procedures for the analysis of DNA species in gel electrophoresis is being demonstrated. It takes advantage of fluorescence photobleaching in order to create a sharp boundary between the stained and the (partially) photobleached DNA. By arbitrarily creating a stained DNA band of narrower width, the sensitivity to detect (averaged) DNA band movements has been increased. This feature permits measurements of time-dependent electrophoretic mobility over very short time periods. The approach can be used to shorten the running time of gel electrophoresis experiment and to increase the resolution because of the sharper boundary and narrower band width. With faster running time, diffusion of both DNA and dye in the gel also becomes less serious. Movement of fluorescence pattern after photobleaching also permits measurements of localized motions when the gel pores are small in comparison with DNA sizes. Experiments demonstrating some aspects of the proposed technique, as well as the anticipated limitations, are presented and discussed. PMID- 1451690 TI - Photodestruction of fluorophores and optimum conditions for trace DNA detection by automated DNA sequencer. AB - Although automated DNA sequencers are becoming popular, their sensitivity in detecting DNA bands is still around 10(-17) mole/band. The sensitivity of a system depends on the laser power, labeling fluorophore, and the fluorescence collecting yield. The emission and photodestruction cross-sections of the fluorophores are critical in optimizing the irradiated laser power and the migration speeds of DNA fragments to achieve high sensitivity. We investigated photodestruction cross-sections of various fluorophores to optimize the irradiation laser power. In addition, we used a cylindrical lens system to improve the fluorescence-collecting yield of a DNA sequencer using side entry laser irradiation. Fluoresceine isothiocyanate (FITC) commonly used in fluorescence studies, is very photo-destructive, the cross-section of the destruction being about 3.8 x 10(-20) cm2 in buffer solution while that of Texas Red is 1.5 x 10(-21) cm2. When the time for DNA fragments to transit through the irradiated region is 11 s, the optimum laser powers are 0.9 mW, with an Ar laser (488 nm) for FITC-DNA, and 18 mW, with an He-Ne laser (594 nm) for Texas Red DNA. We have developed a DNA sequencer, with a cylindrical lens system which improves the fluorescence-collecting efficiency by a factor of 4, and an He-Ne laser (5 mW). Although the sequencer uses a slab gel, an ultra-high sensitivity of 5 x 10( 20) mole/band (S/N-4) was achieved under optimized conditions. PMID- 1451691 TI - Automated magnetic preparation of DNA templates for solid phase sequencing. AB - An integrated protocol for solid-phase DNA sequencing using a robotic work station is described involving magnetic separation of DNA and analysis of the sequencing product by electrophoresis with automated detection of the fluorescently labeled fragments. The method, which is based on magnetic beads in combination with streptavidin-biotin technology, can be used for sequencing both genomic and plasmid DNA. The DNA template is obtained by the polymerase chain reaction (PCR). Protocols to prepare five and ten immobilized samples is described, giving 10 and 20 single-stranded templates, respectively. The magnetic purification steps are performed in a microtiter plate and this allows for an integrated scheme involving a subsequent procedure for automated primer annealing and sequencing reactions. Here, the procedure is examplified by direct genomic sequencing of DNA in blood sample from a human immunodeficiency virus (HIV) infected patient and a cloned human antibody DNA fragment using fluorescently labeled sequencing primers. PMID- 1451692 TI - Fluorescence chemistries for automated primer-directed DNA sequencing. AB - A major limitation in the applicability of automated DNA sequencing instruments has been the difficulty in using user-defined oligonucleotide primers which allow sequencing reactions to start at any specific point in a region of interest. Recently, new chemistries have become available for fluorescent labeling which will begin to facilitate the use of any oligonucleotide primer with automated DNA sequencers. In this report, we describe several methods for automated primer directed DNA sequencing, and compare and discuss the relative merits and limitations of these methods. PMID- 1451693 TI - High-sensitive fluorescent DNA sequencing and its application for detection and mass-screening of point mutations. AB - We describe a rapid and sensitive DNA sequencing method for an automated fluorescent DNA sequencer (AFDS) and its application for detection of point mutations. The method is based on an improved cycle sequencing procedure in which only 10-50 fmol of template DNA is required. Furthermore, it is able to use crude DNA preparation as a template as well as the purified one. Thus, the improved method provided a simplified procedure for sequencing of various types of DNA, including cosmid DNA, in which purification steps were unnecessary. We also developed a novel system for detection of point mutations using AFDS. A set of four lanes is used for the parallel analysis of single-base profiles of four different samples, instead of for the four-base profile of a sample. The AFDS exhibits the base profiles of the samples with four different colors in the analyzed data, which enables us to identify a mutation as an additional peak with a color specific for the lane. The feasibility of our system was tested by analyzing polymerase chain reaction (PCR)-amplified genomic DNAs from four individuals including a carrier of a mutation of C to T. The mutation was clearly identified as an additional "T" peak of a color specific for the carrier. The mutation was also detectable even if 16 individuals including the carrier were simultaneously analyzed on a set of four lanes (four individual samples for each lane). Thus, the novel system is useful for simultaneous detection of mutations in a large number of individual samples. PMID- 1451694 TI - Sequencing by hybridization: towards an automated sequencing of one million M13 clones arrayed on membranes. AB - An immediately applicable variant of the sequencing by hybridization (SBH) method is under development with the capacity to determine up to 100 million base pairs per year. The proposed method comprises six steps: (i) arraying genomic or cDNA M13 clones in 864-well plates (wells of 2 mm); (ii) preparation of DNA samples for spotting by growth of the M13 clones or by polymerase chain reaction (PCR) of the inserts using standard 96-well plates, or plates having as many as 864 correspondingly smaller wells; (iii) robotic spotting of 13,824 samples on an 8 x 12 cm nylon membrane, or correspondingly more, on up to 6 times larger filters, by offset printing with a 96 or 864 0.4 mm pin device; (iv) hybridization of dotted samples with 200-2000 32P-labeled probes comprising 16-256 10-mers having a common 8-mer, 7-mer, or 6-mer in the middle (20 probes per day, each hybridized with 250,000 dots); (v) scoring hybridization signals of 5 million sample-probe pairs per day using storage phosphor plates; and (vi) computing clone order and partial-to-complete DNA sequences using various heuristic algorithms. Genome sequencing based on a combination of this method and gel sequencing techniques may be significantly more economical than gel methods alone. PMID- 1451695 TI - Why can we not sequence thousands of DNA bases on a polyacrylamide gel? AB - Pulsed fields have been remarkably useful at extending the range of DNA molecular sizes that can be separated on agarose gels by controlling the field-induced molecular orientation that often limits the resolution of large molecules. Unfortunately, the same approach seems to be much less effective for DNA sequencing on polyacrylamide gels. We present an experimental and theoretical (modelling) study of DNA sequencing which shows that molecular orientation is indeed not the main limiting factor for sequencing devices that use moderate field intensities and polyacrylamide as a separating matrix. We examine the interplay between electric field intensity, molecular size and resolution, and we suggest different approaches to increase the resolution limit of standard and automated sequencing gels. The theoretical limits of high-field electrophoretic sequencing are also discussed. We conclude that new ideas will be needed to go beyond one kilobase. PMID- 1451696 TI - The prospects for imaging lymph nodes in breast cancer. PMID- 1451697 TI - Quantitative single photon emission tomography: verification for sources in an elliptical water phantom. AB - Accurate absorbed dose calculations are important for a proper dose planning in internal radionuclide therapy. The activity distribution must be measured and the target volume defined. This can be done with single photon emission tomography (SPET) if proper attenuation and scatter correction are employed. This study investigated the calculation of the activity and the volume of different spherical sources. These two parameters are essential for a proper dose calculation. The scatter and attenuation correction method is based on spatially variant scatter functions and density maps. The volume calculation method is based on obtaining a threshold from a grey-level histogram. Both point sources and spheres of different diameters containing technetium-99m were placed in different locations in an elliptical water phantom and imaged by SPET. The activity and the volume of the spheres were calculated from the SPET images and compared with known activities. Results show a quantification of activity within 10% for most of the sources. Important influences on the quantification are (a) the presence of artefacts due to improper reconstruction and (b) the finite spatial resolution which affects the total number of counts within the determined volume. PMID- 1451698 TI - Role of bone scanning in the management of non-united fractures: a clinical study. AB - Technetium-99m methylene diphosphonate (99mTc-MDP) bone scintigraphy was performed in 45 patients (42 male and 3 female) with established non-united fractures to predict the healing response to pulsing electromagnetic field stimulation therapy. The bone scans revealed 3 different scintigraphic patterns. The most frequent pattern was an increased uniform uptake of the tracer at the non-union site (group 1). The second pattern was increased activity at the bone ends with a photon-deficient area between the fracture sites (group 2a) or a generalized decrease in the radionuclide concentration in the region of bone fragments (group 2b). When the scintigraphic pattern did not fit either of the two patterns or when the presence of the cold area between the bone fragments could not be judged with certainty, it was called indeterminate (group 3). All patients underwent pulsing electromagnetic field stimulation. The healing rate was 87.5% and 42.8% in group 1 and group 3 patients, respectively. None of the group 2 patients had any evidence of healing, and they all underwent surgical exploration, revealing complicated non-unions. We conclude that 99mTc bone scintigraphy is a useful tool in determining complicated non-unions and selecting the proper therapy mode. PMID- 1451699 TI - The reliability of the 3-phase bone scan in suspected scaphoid fracture: an inter and intraobserver variability analysis. AB - In the diagnosis of scaphoid fracture, the dynamic phase of the radionuclide bone scan alone has been recommended as an early test. To evaluate the independent reliability of the dynamic and static phases of the 3-phase bone scan in this diagnosis, 3 examiners reviewed the 3-phase bone scans of a series of 60 patients with clinical signs of fracture of the carpal scaphoid and with negative or non diagnostic initial radiographs. The interpretation was performed independently and without the benefit of additional data. The bone scans were reviewed after 1 year by the same observers. The results were analyzed using kappa statistics. The bone scan was suspicious of fracture of the scaphoid in 15 patients. Irrespective of training and experience, the kappa values of the dynamic bone scan between any 2 observers did not exceed 0.57. The kappa values increased significantly when the static phase of the bone scan was examined (> 0.81). The intraobserver variability showed a similar pattern. We conclude that in suspected scaphoid fracture, the dynamic phase of the radionuclide bone scan alone cannot be used as a reliable diagnostic approach because of the low inter- and intraobserver agreement in the interpretation, irrespective of the experience and training of the observer. PMID- 1451700 TI - Scintigraphic evaluation of disease activity in rheumatoid arthritis: a comparison of technetium-99m human non-specific immunoglobulins, leucocytes and albumin nanocolloids. AB - Technetium-99m-labelled, non-specific, polyclonal, human immunoglobulin G (99mTc hIG) has been used to quantify synovial inflammation in rheumatoid arthritis. A comparison was carried out between the scintigraphic results obtained with this tracer, 99mTc-hexamethylpropylene amine oxime-labelled white blood cells (99mTc WBC) and 99mTc-albumin nanocolloids (99mTc-NC). Twenty patients affected by rheumatoid arthritis and suffering from clinically active synovitis were studied with 99mTc-hIG. The number and sites of the involved joints had been previously assessed on the basis of the presence of pain and/or swelling. A radiological examination had already been carried out on all the joints. Two days after the 99mTc-hIG scan, 10 patients (group 1) underwent 99mTc-WBC scintigraphy and the other 10 (group 2) underwent a 99mTc-NC scan. The results show that the results of 99mTc-hIG and 99mTc-NC scans are in agreement with clinical examinations in the majority of cases. However, a certain number of positive joint scans corresponding to negative clinical examinations was found. The numerical distribution of these results according to the radiological stages seems to show that 99mTc-hIG is more useful than 99mTc-NC in the initial phases of the disease. The 99mTc-WBC scan was negative in a consistent percentage of the joints previously assessed as clinically and 99mTc-hIG scan positive. PMID- 1451701 TI - Photopenic defects in marrow-containing skeleton on indium-111 leucocyte scintigraphy: prevalence at sites suspected of osteomyelitis and as an incidental finding. AB - The skeletal distribution of red marrow-containing sites with a decreased uptake of indium-111-labelled leucocytes was examined as part of a retrospective review of 128 consecutive scans in 113 patients. The prevalence of photopenic defects was determined for sites of suspected osteomyelitis and for other skeletal locations included as part of limited or total-body surveys. Of 52 sites suspected of osteomyelitis based upon radiological and clinical data, 21 (40%) demonstrated a decreased leucocyte uptake. The prevalence of photopenia ranged from 79% (11/14) in the spine and 63% (5/8) in the pelvis to 25% (4/16) in the proximal femur and 0% elsewhere in the extremities (0/9) and in the skull (0/3). Fourteen of these 21 defects (67%) were due to active (n = 9) or healed (n = 5) osteomyelitis/discitis. All sites of active osteomyelitis showed destructive changes on correlative radiographs and were associated with infectious processes of more than 1 months duration. Thirty-seven photopenic defects were observed as incidental findings. The prevalence of photopenia as an incidental finding ranged from 0% in the skull, neck and chest to 3%-4% in the thoracolumbar spine and pelvis and 14% in the femoral heads, the latter reflecting primarily bilateral loss of femoral head marrow. No incidentally found photopenic defect reflected active osteomyelitis. At sites in the spine and pelvis with radiologic evidence of bone destruction suggestive of osteomyelitis, an absence of normal red marrow uptake of labelled leucocytes often reflects a variant presentation for active chronic infection. In contrast, incidental photopenia is uncommon at all skeletal sites except the femoral heads, and should not raise concern over unsuspected active osteomyelitis. PMID- 1451702 TI - Liver transplant rejection and cholestasis: comparison of technetium 99m diisopropyl iminodiacetic acid hepatobiliary imaging with liver biopsy. AB - To determine whether the scintigraphic evaluation of technetium-99m diisopropyl iminodiacetic acid (DISIDA) uptake and excretion can distinguish among liver transplant patients with biopsy evidence for rejection, cholestasis or neither condition, we reviewed scintigrams and biopsies in 36 patients. There were 76 scintigrams with corresponding biopsies. Uptake and excretion were graded from image data on scales reflecting normal through severely abnormal values. Biopsies were evaluated for findings of cholestasis and rejection. The majority of scintigrams demonstrated normal uptake (60/75, 80%) and delayed excretion (65/76, 85%), which was most marked immediately after transplantation. One-way analysis of variance showed that the mean excretion values significantly differed between patients with normal biopsies and those with cholestasis and/or rejection (P = 0.0003). However, mean uptake scores demonstrated no statistically significant difference between these two groups of patients (P = 0.1). These findings suggest that 99mTc-DISIDA scintigraphy can differentiate between transplants with and without rejection/cholestasis but not between rejection and cholestasis. If 99mTc DISIDA excretion is normal, rejection and cholestasis are unlikely. PMID- 1451703 TI - Myocardial perfusion damage after mediastinal irradiation for Hodgkin's disease: a thallium-201 single photon emission tomography study. AB - Conflicting data have been reported on the incidence of myocardial abnormalities after mediastinal irradiation for Hodgkin's disease. We studied myocardial perfusion in 31 clinically asymptomatic patients (13 male, 18 female, mean age 35 years) 7 years (range 3-11 years) after mantle field radiotherapy. Thallium-201 tomoscintigraphic data were obtained after exercise, 4 h later and at rest (8-15 days later). Images were analysed visually and quantitatively (sectorial quantification of 201Tl uptake on the bull's eye images of the short-axis slices) compared with those of 35 subjects with a low likelihood of coronary artery disease. Twenty-five tomographic data sets were available. Images were visually abnormal in 21 patients (84%) showing an heterogeneous 201Tl uptake. In 68%, the sectorial 201Tl uptake was lower than the mean 201Tl uptake value minus 2 standard deviations measured in subjects with a low likelihood of coronary artery disease. Significant redistribution (quantitatively assessed > or = 10%) was present in 10 patients (40%). In most of the patients, the location and the shape of the defect(s) could not be anatomically related to an epicardial coronary vessel disease. These results indicate that after mediastinal irradiation the 201Tl myocardial uptake is frequently abnormal. The observed patterns suggest a disease of the small coronary vessels and/or the existence of a myocardial fibrosis rather than epicardial coronary artery disease. PMID- 1451704 TI - Presurgical identification of hibernating myocardium by combined use of technetium-99m hexakis 2-methoxyisobutylisonitrile single photon emission tomography and fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography in patients with coronary artery disease. AB - We tested the possibility of identifying areas of hibernating myocardium by the combined assessment of perfusion and metabolism using single photon emission tomography (SPET) with technetium-99m hexakis 2-methoxyisobutylisonitrile (99mTc MIBI) and positron emission tomography (PET) with fluorine-18 fluoro-2-deoxy-D glucose (18F-FDG). Segmental wall motion, perfusion and 18F-FDG uptake were scored in 5 segments in 14 patients with coronary artery disease (CAD), for a total number of 70 segments. Each subject underwent the following studies prior to and following coronary artery bypass grafting (CABG): first-pass radionuclide angiography, electrocardiography gated planar perfusion scintigraphy and SPET perfusion scintigraphy with 99mTc-MIBI and, after 16 h fasting, 18F-FDG/PET metabolic scintigraphy. Wall motion impairment was either decreased or completely reversed by CABG in 95% of the asynergic segments which exhibited 18F-FDG uptake, whereas it was unmodified in 80% of the asynergic segments with no 18F-FDG uptake. A stepwise multiple logistic analysis was carried out on the asynergic segments to estimate the postoperative probability of wall motion improvement on the basis of the preoperative regional perfusion and metabolic scores. The segments with the highest probability (96%) of functional recovery from preoperative asynergy after revascularization were those with a marked 18F-FDG uptake prior to CABG. High probabilities of functional recovery were also estimated for the segments presenting with moderate and low 18F-FDG uptake (92% and 79%, respectively). A low probability of functional recovery (13%) was estimated in the segments with no 18F-FDG uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451705 TI - Evaluation of myocardial viability with technetium-99m hexakis-2-methoxyisobutyl isonitrile and iodine-123 phenylpentadecanoic acid and single photon emission tomography. AB - The detection of viable myocardium in infarcted regions, i.e. hibernating myocardium, is a major goal in clinical cardiology today. We applied combined planar and single photon emission tomography (SPET) to the non-invasive estimation of the left ventricular ejection fraction (LVEF), myocardial blood flow and free fatty acid uptake in the heart. Of the 31 patients with coronary artery disease, 25 (81%) had had a previous myocardial infarction. All patients had at least one persistent perfusion defect on the stress-rest technetium-99m hexakis-2-methoxyisobutyl isonitrile (Sestamibi) study, and the results revealed 57/124 (46%) persistent perfusion defects. As a part of the perfusion study, the LVEF was measured at rest using the first-pass 99mTc-Sestamibi injection, and the mean LVEF was 47% +/- 9% (mean +/- 1 standard deviation). Iodine-123 phenylpentadecanoic acid (123I-pPPA) imaging at rest was performed within 2 weeks from the perfusion study. Then 6-mm transaxial, sagittal and coronal slices of the perfusion and 123I-pPPA studies were reconstructed. The bull's eye displays of the coronal slices were visually surveyed and divided into 4 quadrants: anterior, lateral, posterior and septal. The following image score was used: 0 = fixed defect, 1 = partial uptake and 2 = normal uptake. Moreover an index of metabolic reserve (MR) was calculated by dividing the bull's eye of the 123I-pPPA study by the bull's eye of resting 99mTc-Sestamibi, and its maximum value was normalized to 100%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451706 TI - Investigation of joint disease. AB - The role of nuclear medicine in the diagnosis and management of the major arthropathies is critically reviewed, with particular reference to osteoarthritis, rheumatoid and similar forms of arthritis, ankylosing spondylitis, non-specific back pain, gout, the neuropathic joint, avascular necrosis, infection and the consequences of prosthetic joint insertion. Attention is drawn both to practical applications and deficiencies in current techniques and knowledge. PMID- 1451707 TI - The small intestine and colon: scintigraphic quantitation of motility in health and disease. AB - Radioisotopes allow accurate quantitation of the pattern and effectiveness of the transit of chyme through the small and large intestines. Abnormalities of small bowel transit can be demonstrated in patients with the irritable bowel syndrome, and patients with chronic idiopathic intestinal pseudo-obstruction due to either a visceral myopathy or neuropathy. In the colon, radioisotopic studies of transit have demonstrated the site of delayed transit in some severely constipated patients. In patients with these disorders of transit, functional studies may influence the choice of medical or surgical therapy although there are few prospective studies which have established their worth in this context. Radioisotope studies can also be utilised to study the effectiveness of delivery of drugs to the small and large bowel, and to study the adequacy of rectal evacuation in patients with a defaecatory disturbance. The low radiation dose and possibility of frequent observations make radioisotope studies valuable for clinical and research studies in functional gastrointestinal disorders. PMID- 1451708 TI - Merkel cell carcinoma and iodine-131 metaiodobenzylguanidine scan. AB - Two cases of Merkel cell carcinoma, a neuroendocrine neoplasia of the skin, investigated with iodine-131 metaiodobenzylguanidine (131I-mIBG) scintigraphy, are reported. Uptake in the tumor was evident only in 1 case. The possible diagnostic and therapeutic role of 131I-mIBG in patients with this rare neoplasm is discussed. PMID- 1451709 TI - Results for a gamma-camera with a new 511-keV collimator. PMID- 1451710 TI - The clinical pharmacology of 6-mercaptopurine. PMID- 1451711 TI - Effects of prior use of non-steroidal anti-inflammatory drugs on renal function and transfusion requirements after upper gastrointestinal haemorrhage. AB - The possibility has been investigated that, after admission to hospital with acute upper gastrointestinal bleeding, patients who have been users of aspirin and non-aspirin non-steroidal anti-inflammatory drugs have poorer baseline renal function, a greater improvement in renal function during their hospital stay, and a larger transfusion requirement than non-users. Patients over 50 years of age admitted to public hospitals with acute upper gastrointestinal bleeding were studied. Creatinine clearance was estimated from serum creatinine and the transfusion requirement was recorded as the number of units of blood transfused on Day 1 and throughout the entire hospital stay. Data were obtained prospectively from case notes and by structured interview. Users of non-steroidal anti-inflammatory drugs were significantly older than non-users. The estimated creatinine clearance on admission to hospital declined with age. Creatinine clearance was 13.2 (95% CI 6.0 to 20.4) ml.min-1 lower in users than non-users of non-aspirin non-steroidal anti-inflammatory drugs. However, the difference was attributable to the older age of the drug users rather than to the drugs themselves. On average, the increase in creatinine clearance during hospital stay was the same in users and non-users of non-aspirin non-steroidal anti inflammatory drugs. Prior use of aspirin had no effect on any measure of renal function. The incidence of blood transfusion was higher in older than in younger patients but neither the incidence of transfusion, nor the transfusion requirement, was different between users and non-users of non-aspirin non steroidal anti-inflammatory drugs and aspirin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451712 TI - Analgesic efficacy of an ibuprofen-codeine combination in patients with pain after removal of lower third molars. AB - A double-blind, randomised analgesic trial was carried out in 165 patients undergoing surgical removal of one impacted lower wisdom tooth. In a two-dose regimen, the analgesic efficacy of the combination ibuprofen-codeine 200 mg : 30 mg was compared with that of acetylsalicylic acid-codeine 500 mg : 30 mg and codeine 30 mg. Each dose was taken when the patient needed pain relief. The intensity of the pain was measured on a visual analogue scale during the 10-h period after the first dose. The mean pain reduction by Dose 1 in patients on ibuprofen-codeine, acetylsalicylic acid-codeine and codeine was 64%, 45% and 26%, respectively, and the mean duration of effect was 8.3, 6.3 and 5.6 h. According to the pain reduction, duration of effect and pain reduction index after Doses 1 and 1 + 2, there was a significant difference between ibuprofen-codeine and the other two drugs. The maximum pain reduction within 4 hours was 84% with ibuprofen codeine. This was significantly different from the reduction achieved both with acetylsalicylic acid-codeine (64%) and codeine (35%). Seventeen patients reported adverse events: 5 on ibuprofen-codeine, 4 on acetylsalicylic acid-codeine and 8 on codeine. The most common events were tiredness and vertigo. It is concluded that the combination ibuprofen-codeine 200 mg : 30 mg had greater analgesic efficacy compared to the combination acetylsalicylic acid-codeine 500 mg : 30 or codeine 30 mg in patients with pain after removal of the lower third molars. PMID- 1451713 TI - Bromocriptine lessens the incidence of mortality in L-dopa-treated parkinsonian patients: prado-study discontinued. AB - L-Dopa supplemented by a peripheral decarboxylase inhibitor is considered the most potent therapeutic regimen prolonging active life in Parkinsonian patients. The long-term benefit of therapy is limited by adverse effects, such as dyskinesia and on-off phenomena, which can be mitigated by the concomitant administration of dopamine agonists, such as bromocriptine. In order to quantify the beneficial impact of early combination therapy, a controlled clinical trial (PRADO: PRA videl1 + DO pa) in patients with early Parkinson's disease was carried out, whereby L-Dopa monotherapy (in a fixed combination with benserazide (DoBe) was being compared with the same combination plus bromocriptine (DoBeBro). Patients were recruited and treated by 101 practising neurologists in the Federal Republic of Germany and in Hungary. Twenty seven clinical university centers cross-checked the patients at regular intervals. The trial started with 3 months of DoBe monotherapy (median dose of 375 mg L-Dopa for both randomized groups) followed by gradual substitution of DoBe by bromocriptine over 3 months in one of the groups (250 mg L-Dopa/10 mg bromocriptine). The target medication was maintained from study months 6 to 54. Parkinsonian symptoms were classified according to the Webster rating scale, the Hoehn and Yahr scale and the Zung Self Rating Depression Scale. Adverse events and life status were checked at regular intervals. Special emphasis was given to motor performance tests. 587 patients (302 in the DoBe group and 285 in the DoBeBro group) were available for intention to-treat analysis. Both groups were homogeneous at baseline in all observed parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451714 TI - Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients. AB - The effect of doxazosin, an alpha 1-adrenoceptor blocking drug, on blood pressure, sensitivity to insulin and serum lipids has been evaluated in 14 hypertensive, non-insulin dependent diabetic patients. The dose was titrated individually upwards from 1 mg until the diastolic blood pressure was below 90 mm Hg, side-effects precluded further dosage increase or the maximum daily dose of 16 mg was achieved. After 12 weeks of treatment (mean doxazosin dose 5.6 +/- 5.1 mg daily), the supine and standing diastolic blood pressure of the patients had declined by about 7 mm Hg, whereas their systolic blood pressure and heart rate were not significantly changed. The metabolic clearance rate of glucose increased from 2.35 to 3.37 ml.min-1.kg-1 during treatment, suggesting improved sensitivity to insulin. Fasting plasma glucose was 11.9 mmol.l-1 before and 10.9 mmol.l-1 after doxazosin therapy (NS). Serum electrolytes and lipids did not change significantly but serum uric acid decreased from 305 to 281 mumol.l-1. Doxazosin may be a useful alternative for the treatment of hypertension in NIDDM patients. PMID- 1451715 TI - Changes in Lp(a) lipoprotein levels during the treatment of hypercholesterolaemia with simvastatin. AB - Thirty-six patients with total serum cholesterol levels above 6.5 mmol/l and Lipoprotein(a) levels above 100 mg.l-1 were evaluated in a 24 week double-blind, placebo controlled, cross-over study to assess the possible changes in Lp(a) during treatment with the HMG CoA reductase inhibitor simvastatin. The median plasma Lp(a) increased from 359 to 464 mg.l-1 during simvastin treatment as compared to placebo (not significant). Individual changes in Lp(a) varied. In a multivariate linear regression analysis the individual change in Lp(a) was correlated with the baseline Lp(a) (r = 0.64), the change in serum triglycerides (r = 0.48) and the baseline apolipoprotein B (r = 0.36). Differences between the Lp(a) phenotypes may explain some of the varied Lp(a) responses. It appears that the effect of simvastatin on the Lp(a) level in individuals is usually insignificant, but in patients with a high Lp(a) simvastatin may further increase it. PMID- 1451716 TI - General well-being during treatment with different ACE-inhibitors: two double blind placebo-controlled cross-over studies in healthy volunteers. AB - Two randomised, double-blind, cross-over studies in healthy volunteers given captopril 50 mg b.d. (n = 37; Study I) or enalapril 20 mg o.d. (n = 40; Study 2) and placebo for 2 weeks have been done to examine general well-being. Subjective experiences were evaluated using the standardised, Minor Symptoms Evaluation profile (MSEP), which was completed during Run-in and on Days 1, 4, 7 and 14 in the morning. In comparison to placebo and the Run-in period, neither captopril nor enalapril affected the MSEP dimensions of Vitality, Contentment and Sleep. Captopril treatment was also assessed by applying the Quality of Life Clinical Questionnaire during Run-in and on Days 7 and 14. No improvement in the quality of life was demonstrated during treatment in comparison with the placebo or the Run-in period. Thus, no mood elevating effect of the ACE-inhibitors captopril and enalapril was demonstrated in healthy volunteers. Cough, which is believed to be a common adverse effect of ACE-inhibitors, was no more frequent during the treatment with captopril or enalapril than with placebo. It is concluded, that short-term treatment with captopril or enalapril is not perceived differently by healthy volunteers than placebo or no treatment at all. Furthermore, the cough associated with ACE-inhibition may be dependent on the duration of treatment, and two weeks was apparently too short for it to emerge. PMID- 1451717 TI - The disposition of valproate and its metabolites in the late first trimester and early second trimester of pregnancy in maternal serum, urine, and amniotic fluid: effect of dose, co-medication, and the presence of spina bifida. AB - We have studied 52 pregnancies in epileptic women taking long-term valproate and have measured the concentrations of the parent compound and 13 of its metabolites by gas chromatography-mass spectrometry in amniotic fluid, maternal serum, and 24 h maternal urine samples. All metabolites of valproate present in the serum could also be detected in the amniotic fluid, although at much lower concentrations. Amniotic fluid concentrations of valproate and several of its metabolites ((E) delta 2-valproate, (2E,3'E) delta 2,3'-valproate, and 3-keto-valproate) correlated with total valproate concentrations as well as with unbound valproate concentrations in maternal serum. We suggest that the amniotic fluid acts as a deep compartment, with slow appearance and disappearance of valproate and its main metabolites. The data further suggest that during the first and early second trimesters of pregnancy the beta-oxidation of valproate decreases. In pregnancies associated with fetal neural tube defects (n = 5) significantly higher daily doses of valproate were used compared with normal pregnancies (n = 47). This resulted in higher concentrations of valproate in maternal serum. However, the metabolite patterns in maternal serum, 24 h urine samples, and amniotic fluid did not show any significant differences in pregnancies with neural tube defects. PMID- 1451718 TI - Phenytoin metabolism during pregnancy. AB - The steady-state 72 h urinary excretion of various phenytoin metabolites has been measured in 10 epileptic women, whose plasma phenytoin concentrations relative to the phenytoin dose fell during pregnancy and rose again post-partum. In later pregnancy and post partum, a mean of 61.3% and 48.9%, respectively, of the total daily phenytoin dose was eliminated as 5-(4-hydroxyphenyl)-5-phenylhydantoin (p HPPH). Even though p-HPPH accounts for not much more than half the total daily phenytoin dose, increased excretion of this metabolite sufficed to account for the elimination of the entire increase in the dose of phenytoin required during pregnancy. There was no definite increase in the excretion of any other (minor) metabolite measured. Thus pregnancy seems not to enhance uniformly the capacity of the various metabolic pathways of phenytoin. PMID- 1451719 TI - Carbamazepine kinetics and adverse effects during and after ethanol exposure in alcoholics and in healthy volunteers. AB - The influence of ethanol on the single-dose kinetics of carbamazepine (400 mg syrup) was assessed in 7 alcoholics after a debauche (mean daily consumption 240 g ethanol) and after 9 days of controlled abstinence, and in 8 healthy volunteers after intake of the drug with and without a single dose of ethanol (25 g). Twelve h after the first test dose of carbamazepine the alcoholics were treated with the drug for 4 days (200 mg tablet b.d.). Carbamazepine was then withheld until a single test dose was given on day 9. Serum levels of carbamazepine and its 10,11 epoxide metabolite were measured by liquid chromatography. Carbamazepine absorption appeared to be delayed in alcoholics, both after debauche and withdrawal, but its bioavailability did not seem to be reduced. Carbamazepine levels were higher and those of its metabolite lower in alcoholics after a debauche than after 9 days of controlled abstinence, but neither was changed in healthy volunteers after the ingestion of carbamazepine together with a single dose of ethanol. The difference may have been due to inhibition of carbamazepine metabolism by ethanol at the high levels attained in alcoholics but not in volunteers. However, it could also be an expression of the unmasking of enzyme induction after ethanol withdrawal. None of the alcoholics had any withdrawal seizures. Despite similar carbamazepine levels, side effects occurred in all volunteers but in none of the alcoholics, indicating that long-term ethanol exposure may promote central nervous adaptation to the acute untoward effects of carbamazepine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451720 TI - Prediction of phenotype for acetylation and for debrisoquine hydroxylation by DNA tests in healthy human volunteers. AB - The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymerase chain reaction (PCR), which also allow for identification of heterozygous carriers of one mutant allele. In the present study, the results of genotyping of 81 healthy European volunteers were compared with the phenotype obtained by the classical biochemical approach using debrisoquine and caffeine as probe drugs. Genotyping correctly predicted all 73 extensive metabolisers (EMs) and 6 out of 8 poor metabolisers (PMs) of debrisoquine. All 48 rapid acetylators and 33 of 35 slow acetylators were predicted. Overall, the DNA analysis result matched the in vivo phenotype in 97.5% of individuals. PMID- 1451721 TI - Steady-state plasma levels of clomipramine and its metabolites: impact of the sparteine/debrisoquine oxidation polymorphism. Danish University Antidepressant Group. AB - After an initial placebo week, 37 depressed inpatients were treated with the fixed dose of 75 mg clomipramine b.d. A sparteine test was carried out during the placebo period and again during the second week of active therapy. Blood for drug assay was collected at the end of the inter-dose interval in the (morning) at weekly intervals. Clomipramine and four metabolites (desmethylclomipramine, didesmethylclomipramine, 8-hydroxyclomipramine, and 8 hydroxydesmethylclomipramine) in plasma were assayed by reversed phase HPLC. The clomipramine and desmethylclomipramine steady-state plasma levels varied by factors of 11 and 9, respectively, and the clomipramine/8-hydroxyclomipramine and desmethylclomipramine/8-hydroxydesmethylclomipramine ratios both varied by 7 fold. During the placebo week, 36 patients were phenotyped as extensive metabolizers (EM) (metabolic ratio, MR, 0.1-2.0), and one patient was phenotyped as a poor metabolizer (PM) (MR > 300). During clomipramine treatment, one patient changed phenotype from EM to PM (MR = 140). In the EM, the median of the MR increased from 0.4 to 2.3. There was a statistically significant correlation between the MR before and during clomipramine treatment, even when the PM was excluded. Neither the steady-state plasma clomipramine levels nor the clomipramine/desmethylclomipramine ratios showed a significant correlation with the MR. In contrast, the desmethylclomipramine and didesmethylclomipramine steady state levels and the desmethylclomipramine/8-hydroxydesmethylclomipramine and clomipramine/8-hydroxyclomipramine ratios showed a significant positive correlation with the MR. The PM had the highest steady-state plasma desmethylclomipramine level and the highest desmethylclomipramine/8 hydroxydesmethylclomipramine ratio. These correlation coefficients (rs) were generally increased when the correlation analyses were based on the MR obtained during clomipramine treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451722 TI - Drug utilization at primary health care level in southern India. AB - Primary health centres provide health care to the majority of the population in developing countries. A drug utilization study was conducted for 1 y at two primary health centres in Pondicherry, India. Information on complaints, diagnosis and drugs prescribed was collected. From the 2953 prescriptions studied, it was found that on an average each patient received 2.71 drugs. Vitamins, antibiotics, analgesics and antihistamines were the most commonly used, accounting for more than 80% of the drugs prescribed. The antimicrobials which constituted one fourth of the drug consumption, comprised sulphonamides, tetracycline and cotrimoxazole. About half of the patients received injections, particularly of the vitamin B Complex and antibiotics. The results will be used to plan intervention strategies for the promotion of rational drug use. PMID- 1451723 TI - Pharmacokinetics of carteolol in patients with impaired renal function. AB - In order to determine the appropriate dosage of carteolol in renal dysfunction, the pharmacokinetics of carteolol has been examined in appropriate patients. The plasma concentrations and urinary excretion of carteolol were investigated in 15 patients with varying degrees of renal impairment during the administration of 5 20 mg carteolol hydrochloride (5 mg/tablet) for 2-45 months. Plasma carteolol levels were linearly correlated with the serum creatinine concentration (r = 0.87) and reciprocally with the creatinine clearance (r = 0.82). The urinary carteolol concentration was correlated with the urinary creatinine concentration (r = 0.69) and the urinary carteolol excretion was also correlated with the creatinine clearance (r = 0.79). These relationships become even closer when the plasma carteolol concentrations and urinary excretion rate of carteolol were factored by the administered tablets. The fractional renal excretion of carteolol was virtually constant at various degrees of renal function, and it always exceeded 100%, which indicates that carteolol was actively secreted, even in patients with renal failure. The estimated tubular secretion rate of carteolol was logarithmically correlated with the fractional renal excretion of carteolol (r = 0.93). The results indicate that the dose of carteolol should be determined according to the degree of renal impairment. PMID- 1451724 TI - Uptake and localisation of O-(beta-hydroxyethyl)-rutosides in the venous wall, measured by laser scanning microscopy. AB - The uptake and localisation of O-(beta-hydroxyethyl)-rutosides (HR) in the venous wall was studied in 8 patients undergoing crossectomy for a varicose long saphenous vein. The fluorescence of cross-sections of the vein wall was measured by laser scanning microscopy, based on the autofluorescence of HR. Four patients (treated group) received 2 x 1.5 g HR IV before surgery, and four (untreated patients) served as controls. Uptake of HR into the veins from treated patients was seen, with a mean fluorescence intensity of 80.9 units compared to 49.4 units in the untreated veins. The increase in fluorescence was clearly demarcated on the endothelial side of the vein wall. It is concluded that HR passes into the vascular wall, where it is localised in the endothelial and sub-endothelial areas. PMID- 1451725 TI - Plasma drug profiles and tolerability of MK-571 (L-660,711), a leukotriene D4 receptor antagonist, in man. AB - We have studied the tolerability and plasma drug profiles of a leukotriene D4 receptor antagonist, MK-571, given intravenously and as an oral solution in two separate trials. Study I (i.v.) involved 2 panels of 6 healthy men in a double blind, alternating, incrementally increasing dose study with single doses up to 1500 mg. There was good tolerability at all doses. Plasma was assayed stereospecifically by HPLC for the S(+) and R(-) enantiomers of MK-571. For each enantiomer AUC values increased more than proportionately with increasing dose, suggesting nonlinear kinetics. The S(+) enantiomer was cleared more rapidly than the R(-) enantiomer. The apparent initial volume of distribution was less than 101 for both enantiomers. Study II (oral) involved 18 healthy subjects in 3 parallel groups who took multiple oral doses of 100, 300, and 600 mg t.i.d. for 31 doses. MK-571 administration was well tolerated, with only mild to moderate gastrointestinal discomfort at the highest dose. Total MK-571 (plasma samples assayed nonstereoselectively) was rapidly absorbed after oral administration, reaching peak concentrations at 1-2 h. Mean 8 h AUC increased from dose 1 to dose 31 in all subjects at all doses, suggesting a modest extent of accumulation (about 50%) of total MK-571 in plasma with a t.i.d. dosage regimen. PMID- 1451726 TI - Dose-dependent kinetics of the enantiomers of MK-571, and LTD4-receptor antagonist. AB - The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i.v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i.v. doses of MK-571 at weekly intervals. The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, 11-, and 2.3 fold. Regardless of dose, the elimination of L 668,018 was more rapid than that of MK-0679. The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition. PMID- 1451727 TI - Population pharmacokinetic parameters for Bayesian monitoring of amikacin therapy in intensive care unit patients. AB - The pharmacokinetics of amikacin has been studied in 40 intensive care unit patients using the bayesian estimation method implemented in the USC PC PACK program of Jelliffe. The volume of the central compartment was significantly higher in these patients than in the reference population, while other pharmacokinetic parameters did not differ significantly from the reference values. The population values may be employed, in addition to those supplied with the software, to adapt dosage regimens of amikacin in ICU patients. PMID- 1451728 TI - Pharmacokinetics of pirmenol in young and elderly subjects. AB - The steady state pharmacokinetics of pirmenol was compared in twelve healthy young (aged 18 to 45 y) and 11 elderly subjects (over 65 y) subjects given pirmenol HCl 100 mg every 12 h for a total of 14 doses. In addition, the single dose pharmacokinetics of pirmenol was determined following a 100 mg oral dose in the young subject group for comparison with the results of repeated administration. In the young subjects, the mean single-dose and steady-state CLR of pirmenol were similar; however, Ae was 29% higher and CL/f was 22% lower at steady state than after the single dose. Steady-state (fourteenth dose) Cmin, Cmax, tmax, lambda z, Ae, CL/f, CLR and V values were similar in the young and elderly subjects. Based on pharmacokinetic considerations, the dosage of pirmenol is unlikely to differ in young and elderly subjects. PMID- 1451729 TI - The effect of a low dose of quinidine on the disposition of flecainide in healthy volunteers. AB - We have studied the effects of quinidine on ECG intervals and on the pharmacokinetics of flecainide and its two metabolites in 6 healthy men in an open randomized crossover study. Flecainide acetate (150 mg) was given as a constant rate i.v. infusion over 30 min. Quinidine (50 mg orally), given the previous evening, did not change the volume of distribution of flecainide (7.9 vs 7.4 l.kg-1), but significantly increased its half-life (8.8 vs 10.7 h). This was attributable to a reduction in total clearance (10.6 vs 8.1 ml.min-1 x kg-1), most of it being accounted for by a reduction in non-renal clearance (7.2 vs 5.2 ml.min-1 x kg-1). The excretion of the metabolites of flecainide over 48 h was significantly reduced. These findings suggest that quinidine inhibits the first step of flecainide metabolism, although it may also reduce its renal clearance, but to a lesser extent (3.5 vs 2.9 ml.min-1 x kg-1). The effects of flecainide on ECG intervals were not altered by quinidine. Thus, quinidine tends to shift extensive metabolizer status for flecainide towards poor metabolizer status and may also alter its renal excretion. PMID- 1451730 TI - Captopril does not interact with the pharmacodynamics and pharmacokinetics of digitoxin in healthy man. AB - The chronic oral administration of 0.07 mg digitoxin o.d. for up to 58 days to 12 healthy volunteers caused a small drop in mean heart rate HR (95% CI: -7.9 to 1.6 beats.min-1), in mean diastolic blood pressure (95% CI: -8.3 to -0.4 mmHg), shortening of the QTc-interval (95% CI: -42 to -19 ms), shortening of the HR corrected pre-ejection period PEPc (95% CI: -16 to -1 ms) and electromechanical systole QS2c (95% CI: -25 to -1 ms), and an increase in the impedance cardiographic Heather index (dZ/dtmax/RZ, 95% CI: 0.3 to 4.3) relative to the baseline measurements before digitalisation. The concomitant administration of 25 mg oral captopril b.d. did not significantly alter these responses relative to the concomitant double-blind administration of placebo, nor did it alter the pharmacokinetic characteristics of plasma digitoxin at steady state. Thus, no relevant change in the pharmacokinetic and pharmacodynamic characteristics of chronically administered digitoxin were induced by concomitant treatment with captopril. PMID- 1451731 TI - Effect of N(G)-nitro-L-arginine methyl ester on the hypotensive and hypertensive responses to 5-hydroxytryptamine in pithed rats. AB - The potential ability of the nitric oxide (NO) synthase inhibitor, NG-nitro-L arginine methyl ester (L-NAME; 1 to 10 mg/kg), to modulate blood pressure responses to 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine (5-CT) and (1 (2,5-dimethoxy-4-iodophenyl)-2-aminopropane) (DOI) was studied in pithed rats. The hypotensive responses to 5-HT in the presence of ketanserin were augmented by L-NAME as well as by phenylephrine infusion, both of which themselves increased blood pressure. L-NAME also tended to prolong the duration of the response of 5 HT. Likewise, the hypotensive responses to 5-CT were potentiated. The magnitude of the hypertensive responses to 5-HT was unaffected by L-NAME or phenylephrine. However, in contrast to phenylephrine, L-NAME prolonged the duration of these responses. The magnitude and duration (middle dose only) of the hypertensive responses to DOI were augmented by L-NAME, but phenylephrine was ineffective. These results suggest that L-NAME increases blood pressure, probably by inhibiting the basal release of NO in animals with a low vascular tone. However, the hypotensive responses to 5-HT and 5-CT seem to be largely independent of NO release by the endothelium, but the hypertensive responses to 5-HT and DOI appear to be limited by the release of NO in the pithed rat. PMID- 1451732 TI - ucb L059, a novel anti-convulsant drug: pharmacological profile in animals. AB - The anticonvulsant activity of ucb L059 ((S)-alpha-ethyl-2-oxo-pyrrolidine acetamide) was evaluated in a range of animal models. ucb L059 was active after oral and intraperitoneal administration in both rats and mice, with a unique profile of action incorporating features in common with several different types of antiepileptic drugs. The compound was active, with ED50 values generally within the range of 5.0-30.0 mg/kg, in inhibiting audiogenic seizures, electrically induced convulsions and convulsions induced chemically by pentylenetetrazole (PTZ), bicuculline, picrotoxin and N-methyl-D-aspartate (NMDA). ucb L059 retarded the development of PTZ-induced kindling in mice and reduced PTZ-induced EEG spike wave discharge in rats. The R enantiomer, ucb L060, had low intrinsic anticonvulsant activity, showing the stereospecificity of action of the molecule although the actual mechanism of action remains unknown. Neurotoxicity, evaluated with an Irwin-type observation test, the rotarod test and open-field exploration, was minimal, with only mild sedation being observed, even at doses 50-100 times higher than the anticonvulsant doses; at pharmacologically active doses, the animals appeared calm but slightly more active. ucb L059 thus presents as an orally active, safe, broad-spectrum anticonvulsant agent, with potential antiepileptogenic and anti-absence actions. PMID- 1451733 TI - Effects of phorbol ester on lower urinary tract smooth muscles in rabbits. AB - The contractile effects of phorbol 12,13-dibutyrate (PDBu) on rabbit urinary bladder dome and urethra were investigated using muscle bath techniques. PDBu caused concentration-dependent contractions in both tissues, and these responses were not affected by pretreatment with atropine, phentolamine, hexamethonium or indomethacin. In both tissues, 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H 7), a potent inhibitor of protein kinase C (PKC), inhibited PDBu-induced contractions in a concentration-dependent manner. The maximum PDBu-induced contractions in bladder dome and urethra were 33.5 +/- 3.4 and 33.3 +/- 4.1% of KCl-induced maximum contractions, respectively. In Ca(2+)-free solution or after pretreatment with nifedipine (10(-6) M), PDBu-induced contractions were reduced but not completely abolished. Although pretreatment with PDBu (10(-8) M) did not have a significant effect on the contractile responses induced by carbachol (in bladder dome) and phenylephrine (in urethra), pretreatment with H-7 (100 microM) had an inhibitory effect on carbachol- and phenylephrine-induced contractions; tonic phase contractions were more sensitive than phasic contractions. These results indicate that PDBu has significant contractile effects in rabbit bladder dome and urethra, and that the effects may be partly mediated by activation of PKC. PKC activation might also contribute to agonist-induced contractile responses in these tissues. PMID- 1451734 TI - Effect of Mn2+ on neonatal and adult rat heart: initial depression and late augmentation of contractile force. AB - In the present study, we examined the inotropic effect of Mn2+ on adult and neonatal rat myocardia, contraction of which is known to be highly dependent on Ca2+ release from the sarcoplasmic reticulum and trans-sarcolemmal Ca2+ influx, respectively. Mn2+ produced an initial negative inotropic effect followed by a late augmentation of contractile force in both neonatal and adult preparations, accompanied by marked prolongation of the contraction duration. The attenuation of the late augmentation by ryanodine was greater in the adult while the effect of nicardipine was greater in the neonate, which was similar to the effects of the two drugs in the absence of Mn2+. We tentatively concluded that Mn2+ produces late augmentation of the contractile force in neonatal and adult rat myocardia through some action on the general mechanism of force development, rather than by acting specifically on the sarcoplasmic reticulum. PMID- 1451735 TI - Dopaminergic modulation of pilocarpine-induced motor seizures in the rat: the role of hippocampal dopamine D1 receptors. AB - The present study addressed the role of dopamine D1 receptors in pilocarpine induced motor seizures in rats. Bilateral pretreatment of the hippocampus with the D1 agonist SKF 38393 (0.1-5 micrograms) did not alter the animals' sensitivity to a threshold (200 mg/kg i.p.) or fully convulsant dose (600 mg/kg i.p.) of pilocarpine, as compared to hippocampal saline-treated controls. Similarly, direct injection of pilocarpine (200 micrograms per side) into both hippocampi elicited low level seizure activity that was not modified by SKF 38393, either coadministered (2 micrograms per side) or injected systemically (30 mg/kg i.p.). On the other hand, intrahippocampal microinjections of the D1 antagonist, SCH 23390 (2 micrograms per side), whilst unable to prevent epileptogenesis to 600 mg/kg pilocarpine, delayed the onset of seizures and reduced their severity. These results suggest that hippocampal dopamine lowers the seizure threshold by activating D1 receptors, an effect which is only disclosed by D1 receptor blockade and is not surmountable by additional D1 stimulation. PMID- 1451736 TI - Influence of pertussis toxin on thermic responses to morphine and neurotensin in rats. AB - The influence of pertussis toxin (PTX) on thermic responses elicited by morphine and neurotensin was evaluated in unrestrained rats kept at 22 degrees C. High doses of morphine (9-36 micrograms/rat i.c.v.) lowered body temperature and low doses (1.25, 2.5 micrograms/rat i.c.v.) produced hyperthermia. The hyperthermic effect was more resistant than the hypothermic effect to naloxone antagonism. Neurotensin (50, 100 micrograms/rat i.c.v.) induced marked hypothermia followed by hyperthermia. I.c.v. injection of PTX (1 microgram), six days before morphine (18 micrograms/rat i.c.v.), replaced the opiate hypothermia by consistent hyperthermia and reduced by 60% the hyperthermia elicited by morphine (2.5 micrograms/rat i.c.v.). The toxin also affected the thermic responses induced by neurotensin (50 micrograms/rat i.c.v.) administered six days after PTX (1 microgram/rat i.c.v.). The initial hypothermia was enhanced by 173% and the late hyperthermia was fully antagonized. It thus appears that PTX-sensitive G-proteins play different roles in the molecular events underlying the thermoregulatory responses to morphine and neurotensin. PMID- 1451737 TI - Pancopride, a potent and long-acting 5-HT3 receptor antagonist, is orally effective against anticancer drug-evoked emesis. AB - Pancopride ((+-)N-(1-azabicyclo-[2,2,2]-oct-3-yl)-2-cyclopropylmethoxy-4-ami no-5 chlorobenzamide) is a new potent and selective 5-HT3 receptor antagonist, orally and parenterally effective against cytotoxic drug-induced emesis. In vitro, pancopride displayed high affinity (Ki = 0.40 nM) for [3H]GR65630-labelled 5-HT3 recognition sites in membranes from the cortex of rat brains. In vivo, pancopride antagonized 5-HT-induced bradycardia in anaesthetized rats when administered i.v. 5 min (ID50 = 0.56 microgram/kg) or p.o. 60 min (ID50 = 8.7 micrograms/kg) before 5-HT challenge. A single oral dose (10 micrograms/kg) of pancopride produced a significant inhibition of the bradycardic reflex over an 8-h period. Pancopride dose dependently inhibited the number of vomiting episodes and delayed the onset of vomiting induced by cisplatin in dogs (ID50 = 3.6 micrograms/kg i.v. and 7.1 micrograms/kg p.o.). Pancopride was also effective in blocking mechlorethamine- and dacarbazine-induced emesis. Unlike metoclopramide, pancopride was shown to lack any measurable antidopaminergic activity both in vitro and in vivo. These results support clinical data, indicating that pancopride will be a useful drug for treating cytostatic-induced emesis in humans. PMID- 1451738 TI - Dexamethasone attenuates altered insulin secretion elicited by interleukin-1 beta in HIT cells. AB - The effects of dexamethasone on the modulation of insulin secretion by recombinant human interleukin-1 beta (IL-1) were examined in HIT-T 15 cells. The addition of IL-1 from 1.2 x 10(-8) to 10(-10) M increased insulin secretion in the 0-4-h period after IL-1 administration and prostaglandin E2 (PGE2) production was suppressed by IL-1 from 1.2 x 10(-8) to 10(-12) M. At all doses used, IL-1 inhibited insulin secretion in the 4-24-h period after IL-1 administration and PGE2 levels were increased in the culture medium. In the second experiment, the addition of 10(-7) M dexamethasone prevented the inhibitory effects of IL-1 on insulin secretion. In the third experiment, dexamethasone at 10(-7) M attenuated both the short-term stimulation of insulin release and the long-term suppression of insulin release caused by IL-1. It also prevented the effects of IL-1 on PGE2 production. The present studies suggest that dexamethasone may have a suppressive action on the effects of IL-1 on in vitro insulin secretion. PMID- 1451740 TI - Effects of baclofen on amino acid release. AB - This study showed the effects of baclofen on endogenous excitatory (Glu and Asp) and non-excitatory (Tau, Gly and Ala) amino acid release. (A) Release was stimulated by K+ 30 mM in rat frontal cortex slices in vitro (evoked release in ng/g tissue per 5 min): 3739 +/- 215 (Asp), 3429 +/- 357 (Glu), 763 +/- 181 (Tau), 945 +/- 71 (Ala), 468 +/- 44 (Gly). (B) Release was largely Ca(2+) dependent for all amino acids but Ca(2+)-independent release was observed for Asp and Glu (29 and 32%, of total evoked release respectively). (C) Ca(2+)-dependent release was inhibited by baclofen 100 microM (% of inhibition taking as 100%, the Ca(2+)-dependent release in the absence of baclofen): 46 (Asp), 96 (Glu) (85% inhibition by baclofen 10 microM), 100 (Tau), 77 (Ala). Ca(2+)-independent release was inhibited: 87 and 88% (Asp), 85 and 95% (Glu) by baclofen 10 and 100 microM respectively. It is concluded that baclofen at a high concentration inhibits the evoked release of Glu, Asp, Tau and Ala due to inhibition of the Ca(2+)-dependent fraction and also of the Ca(2+)-independent component in the case of Glu and Asp. Baclofen at a low concentration inhibits only Glu- and Asp evoked release (total release) due to inhibition of both Ca(2+)-dependent and independent fractions in the case of Glu and to inhibition of the Ca(2+) independent fraction in the case of Asp. The possibility that baclofen might affect the Ca(2+)-independent carrier-mediated release of Glu-Asp is discussed. PMID- 1451739 TI - The vasoconstrictor action of big endothelin-1 is phosphoramidon-sensitive in rabbit saphenous artery, but not in saphenous vein. AB - The effects of big endothelin-1 and endothelin-1 on vascular reactivity were compared in isolated rabbit saphenous artery and vein. The contractile potency of endothelin-1 was three times higher in the vein than in the artery. In contrast, big endothelin-1 was two times more effective in the artery. Phosphoramidon (100 microM), a metalloproteinase inhibitor, antagonised the contractile action of big endothelin-1 in the artery but not in the vein. These data suggest that the biosynthetic pathway leading to the formation of endothelin differs in arterial and venous vessels. PMID- 1451741 TI - Involvement of haloperidol-sensitive sigma-sites in antitussive effects. AB - The effects of selective sigma-ligands on the capsaicin-induced cough reflex in rats were studied. Intraperitoneal injection of (+)-N-allylnormetazocine ((+)-SKF 10,047) and N,N'-di(ortho-tolyl)guanidine (DTG) in doses that ranged from 0.3 to 3.0 mg/kg decreased the number of coughs dose dependently. The antitussive effects of these sigma-ligands were significantly attenuated by pretreatment with haloperidol. Pretreatment with haloperidol also markedly reduced the antitussive effects of (+/-)-pentazocine and dextromethorphan. These results suggest that haloperidol-sensitive sigma-sites may be involved in the regulation of coughs. PMID- 1451742 TI - Investigation into the 5-hydroxytryptamine-induced relaxation of the circular smooth muscle of guinea-pig stomach fundus. AB - The 5-HT receptor that mediates relaxation of circular muscle strips of the guinea-pig stomach fundus under resting tone was investigated. Concentration dependent relaxation was obtained in the presence of atropine (0.2 microM) with 5 hydroxytryptamine (5-HT) (apparent mean pEC50 value, 5.27), 5 carboxamidotryptamine (7.35), 5-methoxytryptamine (4.98) and 5-methyltryptamine (4.58). 1-(m-Trifluoromethyl-phenyl)piperazine and 8-hydroxy-2-(di-n- propylamino)tetralin acted as partial agonists while 2-methyl-5 hydroxytryptamine, alpha-methyl-5-hydroxytryptamine, sumatriptan, metoclopramide and cisapride had little or no effect on the guinea-pig stomach fundus. The concentration-response curve for 5-HT was not affected by tetrodotoxin (0.3 microM), guanethidine (5 microM) or indomethacin (2 microM), suggesting that the relaxation is non-neuronal in origin and is independent of the release of catecholamines or prostanoids. The non-selective 5-HT receptor antagonist, metitepine (0.03-0.1 microM), the 5-HT1C/5-HT2 receptor antagonists, mianserin (0.3-1 microM), pizotifen (0.3-1 microM), ketanserin (3-10 microM), and the 5 HT1A/5-HT2 receptor antagonist, spiperone (3 microM), shifted the concentration response curves for 5-HT to the right. A 5-HT3 receptor antagonist, ICS205-930 (1 microM), propranolol (1 microM) and phentolamine (1 microM) failed to block the 5 HT-induced relaxation. In conclusion, the results found with agonists and antagonists are compatible with the view that a 5-HT1-like receptor is involved in 5-HT-induced direct relaxation of circular muscle of guinea-pig stomach fundus. PMID- 1451743 TI - Neuroprotective effect of 5-HT3 receptor antagonist on ischemia-induced decrease in CA1 field potential in rat hippocampal slices. AB - The effect of 5-HT3 receptor agonists and antagonists on the hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 field potential elicited by stimulation of Schaffer collaterals was investigated using rat hippocampal slices. Treatment with the 5-HT3 receptor agonist, 2-methyl-5-HT (1-10 microM), exacerbated the ischemia-induced decreased in CA1 field potential, whereas treatment with the 5 HT3 receptor antagonist, Y-25130 (0.1-100 microM), or the 5-HT2 receptor antagonist, ketanserin (10, 100 microM), produced dose-dependent neuroprotection against the ischemia-induced decrease. However, in normal non-ischemic solution these treatments did not significantly change the CA1 field potential. The protective action of Y-25130 was blocked by co-treatment with 2-methyl-5-HT. The magnitude of protection in the Y-25130-treated group (EC50, 1.8 microM) was about 20 times greater than that in the ketanserin-treated group (EC50, 33 microM). The present study demonstrated that stimulation of 5-HT3 receptors plays a detrimental role in the development of ischemic damage, whereas blockade of the 5 HT3 receptor plays a neuroprotective role in ischemic damage, suggesting a facilitatory role of 5-HT neurons in ischemia-induced neuronal deficits. PMID- 1451744 TI - Effects of ouabain on muscle tension and intracellular Ca2+ level in guinea-pig aorta. AB - The effects of ouabain on muscle tension and the intracellular Ca2+ level ([Ca2+]i) were examined in guinea-pig aorta loaded with fura-2. Ouabain caused a gradual and sustained increase in both [Ca2+]i and muscle tension. There was a positive correlation between these two parameters. In Ca(2+)-free solution, ouabain did not affect either [Ca2+]i or muscle tension, suggesting that the ouabain-induced increase in [Ca2+]i was not due to Ca2+ release from storage sites. The ouabain-induced increase in [Ca2+]i and muscle tension was inhibited by Ni2+, which inhibits the Na+/Ca2+ exchanger, but not by verapamil. Furthermore, anionic and cationic amphiphiles were used as modulators of the Na+/Ca2+ exchanger. Sodium dodecyl sulfate accelerated the responses to ouabain, whereas dodecyltrimethylammonium bromide inhibited them. These results suggest that in the guinea-pig aorta, ouabain induces contraction by increasing the Ca2+ influx through the Na+/Ca2+ exchanger on the plasma membrane, but not through verapamil-sensitive Ca2+ channels. PMID- 1451745 TI - Analgesic effect of salmon-calcitonin administered by two routes. Effect on morphine analgesia. AB - We compared the analgesia induced by intraperitoneally (i.p.) and intracerebroventricularly (i.c.v.) administered salmon-calcitonin (S-CT), using the hot-plate test and the writhing test. The influence of the route of administration on the analgesia induced by morphine was also studied. After i.p. administration the analgesic effect was observed only in the writhing test. When S-CT was administered i.c.v., analgesia was observed in both tests, although it was greater in the writhing test than in the hot-plate test. I.c.v. injected S-CT increased the analgesia of i.p. injected morphine. Our results provide new information about the analgesic effect of S-CT and suggest that central mechanisms are involved. PMID- 1451746 TI - Action of externally applied ATP on rat reticulospinal vasomotor neurons. AB - In anesthetized rats, iontophoretic application of ATP excited the spinal cord projection neurons in the rostral ventrolateral reticular nucleus of the medulla oblongata. The neuronal response to ATP was mimicked and then blocked by alpha,beta-methylene-ATP, a metabolically stable ATP analogue, and the response was abolished by suramin. Microinjections of ATP (3-100 pmol) into the rostral ventrolateral medulla produced a powerful pressor response. The results suggest that ATP may function as a neurotransmitter or neuromodulator involved in medullary regulation of cardiovascular functions. PMID- 1451747 TI - D-cycloserine reverses the working memory impairment of hippocampal-lesioned rats in a spatial learning task. AB - It is shown that D-cycloserine has cognition-enhancing properties in quinolinic acid hippocampal-lesioned rats. Lesioned rats had a severe impairment of working memory in an allocentric spatial reversal paradigm in the 8-arm maze, and performance could be restored with 12 mg/kg i.p. D-cycloserine, given 30 min before testing. The present findings favour the testing of D-cycloserine for clinical efficacy in patients with Alzheimer's disease with loss of pyramidal neurons and disconnected glycine-NMDA receptor activation. PMID- 1451748 TI - Ethanol can inhibit nitric oxide production. AB - Endogenous nitric oxide (NO) in exhaled air from anaesthetized rabbits was monitored by chemiluminescence. Ethanol (3-30 mmol kg-1) infused i.v. dose dependently reduced the levels of exhaled NO, with an IC50 of 23 +/- 3 mmol kg-1. L-Arginine (1 g kg-1) did not reverse the effect of ethanol. These results demonstrate the inhibition of NO formation by ethanol in vivo. PMID- 1451749 TI - [Immunopathology of lupus nephritis revealed in the mouse models]. PMID- 1451750 TI - Postnatal behavioral development in methylazoxymethanol-induced microcephalic rats--a behavioral teratology study. AB - Behavioral testings in methylazoxymethanol (MAM)-induced microcephalic rats were conducted. Pregnant Sprague-Dawley rats were treated intraperitoneally with 0, 20 or 40 mg/kg of MAM once a day on day 14 of gestation and were allowed to delivery. Male pups from each litter were examined for open field test at 6 weeks of age and shuttle-box avoidance test at 7 weeks or more of age. In the open field activity of pups, the counts of ambulation and locomoting distance in 40 mg/kg group have increased significantly as compared with those in control group. In the shuttle-box avoidance test, the avoidance response rate was dose dependently high in the session of the 1st day. As to the interaction between the avoidance response rate and sequence of sessions, however, the avoidance response rate in 40 mg/kg group was significantly low. Rate of the rats with errors and number of response during the intertrial interval was significantly high in 40 mg/kg group. Thus, we could demonstrate functional disturbance in the memory retaining ability in utero MAM-exposed rats. PMID- 1451751 TI - [Biological effects of exposure to high frequency electromagnetics on rabbits and guinea pigs]. AB - To investigate the biological effects of exposure to feeble high frequency electromagnetism, skin surface temperature, blood vessel (arterioles and venules) diameter were examined, using infrared thermography, a laser doppler flowmeter, and a video microscope, respectively, in the ear of rabbits. After exposing the ear of rabbits to high frequency electromagnetism value of 9 MHz for 15 minutes, continued rising of local temperature was demonstrated. Though dilatation of arterioles was not seen. In addition, venules tended to dilate and blood flow also to increase, and microcirculation was accelerated at the site where electromagnetism was exposed. Hazardous effects of long term exposures of high frequency electromagnetism (9 MHz for 30 days, 8 hours/day) on guinea pigs were not observed in their behavior, food consumption, body and organ weights, hematological and biochemical values, macroscopic and microscopic findings on autopsy. PMID- 1451752 TI - [Morphometric and immunohistochemical studies of the suprachiasmatic nucleus in the hereditary microphthalmic rat]. AB - Morphometric and immunohistochemical analyses of the suprachiasmatic nucleus (SCN) were performed on hereditary microphthalmic rats. In normal rats, the number of cells and the volume of the SCN were 11, 631 and 6.7 x 10(-2) mm3 (an average taken from 12 SCNs). However, the neuronal population and volume of the SCN in hereditary microphthalmic rats were 7,450 and 4.5 x 10(-2) mm3 (an average taken from 14 SCNs), respectively. There were no significant differences in the size of neurons between normal and microphthalmic SCN neurons. Immunohistochemical studies showed that a considerable number of antivasopressin positive neurons were present in microphthalmic rats, despite their lack of the optic nerve. However, further detailed studies revealed that the number of antivasopressin positive neurons present in microphthalmic rats was only 68% of those found in normal rats. These findings suggest that the complete development of the SCN and vasopressin neurons depends on the visual input. PMID- 1451753 TI - [Cryopreservation of unfertilized rat oocytes by ultrarapid freezing]. AB - Unfertilized rat oocytes were placed in a highly concentrated solution of cryoprotectant (DAP 224:2M dimethylsulphoxide, 2M acetamide, 4M propylene glycol in PB1) in 0.5 ml sampling tubes and then immediately immersed into liquid nitrogen; thawing was conducted in a 37 degrees C waterbath. After thawing, 630 out of 968 oocytes (65.1%) were morphologically normal. After insemination in vitro of cryopreserved oocytes, the proportion of pronuclear oocytes with spermatail (s), male (s) and female pronuclei (8-10 h post insemination), and 2 cell embryos with two identical blastomeres (28-30 h post insemination) was 60.8% (152/250) and 29.8% (39/131), respectively. One hundred and fifty oocytes that were judged as pronuclear oocytes under the inverted microscope 8-10 h after insemination were transferred to the oviducts of pseudopregnant recipients; 18.7% (28/150) of the oocytes developed to normal young. PMID- 1451754 TI - The domestication of Crocidura dsinezumi as a new laboratory animal. AB - The dsinezumi shrew (Crocidura dsinezumi), a small insectivore, has been bred for the first time as a laboratory animal. The original animals were captured using Sherman's live traps and transferred into wooden cages. After several generations they were housed in plastic cages. Their diet consisted of trout pellets, cat food, and water provided ad libitum. Monogamous pairs were housed together for 2 3 weeks for mating, and the male was separated from the female during delivery and nursing. In captivity, the reproductive activity was observed throughout the year and the gestation period was estimated at 28-30 days with a litter size of between 1 and 4 pups. Pups grew very rapidly, and reached adult body size (mean: male, 9.7 g; female, 8.3 g) and sexual maturation at 6-8 weeks of age. The reproductive life was estimated at one and a half years, while the longevity was approximately 2 years. PMID- 1451755 TI - Spontaneous lesions in cynomolgus monkeys used in toxicity studies. AB - Spontaneous lesions in wild-caught, laboratory-maintained cynomolgus monkeys used in drug-toxicity studies were examined histopathologically in an effort to better distinguish toxic changes from spontaneous lesions and assess the toxicity of drugs more exactly. In the liver and kidney, where toxic changes are observed frequently, many spontaneous lesions were observed. Infiltration of mononuclear cells, vacuolization of the hepatocytes, dilatation of the renal tubules, and vacuolization of the renal epithelia were observed at a relatively high frequency. It is considered important to examine these changes carefully, because they closely resemble the changes recognized as toxic. Deposition of brownish pigment was observed in various organs such as the liver, kidney, spleen, intestinal tract, lung and brain, however the type of pigment differed among the organs, and histochemical examination revealed anthracosis or accumulation of hemosiderin, or melanin. Since the monkeys were caught in the wild, many parasitic lesions were observed especially in the large intestine and liver. Helminthous worms were frequently observed in the granulomas in the large intestine, however, no parasites were observed in the granulomas in the liver. Such lesions in the liver may be misinterpreted as toxic changes, when only scars or inflammatory lesions are observed. PMID- 1451756 TI - [Immunocytochemical and morphometric studies on the development of renin immunoreactive cells in the rat kidney]. AB - The development of renin-immunoreactive cells was immunocytochemically studied in Wistar-Imamichi rats. The renin-immunoreactivity was localized in the walls of the abdominal aorta, renal artery and arterioles in the kidney. The renin immunoreactive cells converged with the progress of development from the renal artery via several arterioles to the afferent arteriole in the kidney. In the afferent arteriole, renin-immunoreactive cells appeared only in those of matured glomeruli. The matured glomerulus first appeared at 17 days of gestation followed by the initial appearance of renin-immunoreactive cells at 18 days. The juxtaglomerular index showing the relation between matured glomeruli and renin immunoreactive cells increased rapidly until 20 days of gestation, shifted thereafter at a level similar to that at 20 days until 7 days after birth, and increased again until 20 days after birth. Although the area of the transverse section at the hilus of the kidney increased all through the period examined, the number of matured glomeruli increased rapidly from 17 days of gestation to 7 days after birth and maintained a fixed level thereafter. This led to the decrease in the number of matured glomeruli per unit area after 7 days after birth. The fine structure of renin-immunoreactive cells showed no difference according to their sites of localization. PMID- 1451757 TI - [Effect of sex hormones on the onset of diabetic syndrome in WBN/Kob rats]. AB - The effects of sex hormone on diabetic conditions were investigated in WBN/Kob strain rats, i.e., castrated or spayed, hormone-treated, and non-treated rats. The effects of sex hormone on glycosuria, body-weight change, glucose tolerance and histopathology of the pancreas were compared among these animals. There were no abnormal changes in these parameters in the non-treated females and estrogen treated males. The glycosuria began to be observed from the age of about 30 weeks in the non-treated group and from the age of 52 weeks in the castrated group. In the female animals, this symptom began to appear from the age of 55 weeks in the testosterone-treated group and from the age of 72 weeks in the spayed group. Before the onset of the diabetic symptoms, glucose tolerance was impaired in these animals. Body weights of the castrated and estrogen-treated males were lower than that of the non-treated males, especially in the estrogen-treated males. Those of the spayed and testosterone-treated females were much heavier than that of the non-treated females. Testosterone treatment accelerated body weight gain in the spayed female animals. Histopathological examination of the pancreas revealed atrophy of the aciner tissue and atrophy and disappearance of the islet cells similar to those of the non-treated WBN/Kob male rats in the castrated males, spayed females and testosterone-treated females. However, these changes were not observed in the non-treated females or estrogen-treated males. These findings suggest that female hormone suppressed the onset of hyperglycemia along with glycosuria and male hormone accelerates the onset of hyperglycemia in the WBN/Kob rats. PMID- 1451758 TI - Fine structure of the parotid gland in the crest-tailed marsupial-rat (Dasyuroides byrnei). AB - The parotid gland of Dasyuroides byrnei was examined by light microscopy, and transmission and scanning electron microscopy. The acini were composed predominantly of seromucous cells with a few mucous cells. The seromucous cells were light or dark cells containing acidophilic spherical granules of moderate to high electron density and had well-developed cytoplasmic organelles-ordinary mitochondria and large mitochondria with tubular cristae, RER with vesicular or tubular elements, and Golgi apparatus with lamellae, vesicles and vacuoles. The mucous cells had basophilic amorphous granules of low electron density, like those of ordinary mucous cells. The intercalated ducts were composed of simple cuboidal light cells having a few electron-dense granules. The striated ducts consisted of tall columnar light cells containing numerous vesicles and mitochondria with tubular cristae, the same as found in acinar seromucous cells. PMID- 1451759 TI - [Hematological and serum biochemical effects of nursing on the mother in cynomolgus monkeys (Macaca fascicularis)]. AB - The effects of nursing on maternal hematological and serum biochemical values were analyzed in cynomolgus monkeys reared in indoor cages at Tsukuba Primate Center. In our breeding system, infants are usually separated from their mothers at the age of 121 to 180 days. Mother monkeys of such infants were studied hematologically and biochemically (Group B), as were mother monkeys who happened to have nursed their infants past 181 days after parturition (Group A). During the period with their infants, mother monkeys in the latter group showed lower white blood cell counts (WBC) and higher red blood cell counts (RBC), hematocrit values (Ht) and blood urea nitrogen concentrations (BUN) than the mother monkeys who had been separated from their infants. Also, serum calcium concentrations (Ca) were decreased with prolonged nursing periods, indicating that lactation by the mother monkey probably continues even for a period from 181 days to about one year after parturition if she nurses her infant. Lactation during this period may accelerate hematogenesis and protein metabolism in the mother monkey. PMID- 1451760 TI - [Diurnal rhythm of drinking activity in the house musk shrew]. AB - A diurnal rhythm of drinking activity in 7 male and 6 female house musk shrews (Jic: SUN) aged about one year was observed over a period of 10 days under a schedule of 12 hr light and 12 hr darkness (light on at 07:00). In general, the pattern of drinking activity was similar among both sexes, with around 24-hr diurnal rhythm. A few typical drinking patterns of these animals were represented as follows: 1) Drinking interval was very close in the dark phase, while it was a little too sparse in the light phase (n = 4). 2) Its interval remains stationary through a whole day (n = 5). 3) Drinking was performed between the latter half of light and the first half of dark phases (n = 4). PMID- 1451761 TI - Production of normal young following insemination of frozen-thawed mouse spermatozoa into fallopian tubes of pseudopregnant females. AB - Mouse epididymal spermatozoa in the cryopreservation solution (18% raffinose and 3% skim milk in distilled water) were frozen and stored at -196 degrees C, and later thawed at room temperature. The thawed sperm suspension was inseminated into the Fallopian tubes containing ovulated oocytes in pseudopregnant females on the day of finding the vaginal plug. Five out of 12 females gave birth to 28 Young (5.6 per liter). PMID- 1451762 TI - Behavioral study on the gracile axonal dystrophy (GAD) mutant mouse. AB - We investigated motor function and pain sensation in the gracile axonal dystrophy (GAD) mutant mouse, using the tail-flick test and the rotarod test. GAD (gad/gad) and normal sib mice (gad/+ or +/+) were used between 5 and 11 weeks of age, during which time the behavioral signs of GAD mice shifted from sensory ataxia (about 4 to 8 weeks of age) to paresis (after about 9 weeks of age). In the tail flick test, significant shortening of latency was observed at 6 and 8 weeks of age in female GAD mice, in comparison with normal female mice. This may be related to dysfunction or degeneration of axons in the fasiculus gracilis, whose collaterals are thought to control the transmission of nociceptive information. In the rotarod test, a cumulative chi 2 test showed significant reduction in the performance times of GAD mice beginning at 5 and 6 weeks of age in males and females, respectively, indicating that the rotarod test can detect the development of motor incoordination as early as these ages. The performance times of GAD mice dropped sharply from 9 weeks of age onwards, and this is believed to reflect the progression of paresis. The rotarod test therefore appears to be a good method of quantifying behavioral changes in GAD mice and to be applicable both to objective selection of GAD mice before 8 weeks of age and to evaluation of drugs to treat ataxia or paresis. PMID- 1451763 TI - Lymphocyte blastogenesis in hairless dogs following stimulation by various mitogens. AB - Lymphocyte blastogenesis in hairless descendants of Mexican hairless dogs was examined using the following mitogens: phytohemagglutinin (PHA-M), Concanavalin A (Con A), lipopolysaccharide (LPS) and pokeweed mitogen (PWM). Blastogenetic responses to these mitogens were measured by glucose consumption test (GCT) and compared with those of haired beagle dogs. The response to PHA-M was significantly less in the hairless dogs than in the beagles. No significant differences in the responses to Con A, PWM and LPS were recognized. These results indicated T-cell dysfunction in the hairless dogs, coinciding with our previous work showing reduction of the delayed-type hypersensitivity reaction and early degeneration of the thymus. PMID- 1451764 TI - [The influence of serum separators on biochemical values in experimental animals]. AB - The influence of three serum separators, A, B and C, on biochemical values was examined. With A or B, changes in the values of ChE, LAP, UN, K, P, Cl and Ca in rat serum; ChE, UN, Cl and Ca in dog serum; and K and P in monkey serum took place over a period of 20 min after blood collection. Therefore, the biochemical values of whole blood were considered to be stable after 20 min. Thus, biochemical tests were conducted on serum from the three serum separators after allowing the blood to stand 20 min. The values obtained for each separator were not markedly different from those of the control. These results suggest that a serum separator is useful for separation of serum of experimental animals under the proper conditions. PMID- 1451765 TI - [Cryopreservation of spermatozoa of a transgenic mouse]. AB - Spermatozoa of a homozygous transgenic mouse, in which the firefly luciferase gene was expressed under the control of beta-actin promoter, were frozen at -196 degrees C. One fourth of the frozen sperm was later thawed and used for in vitro fertilization. Thirty-six of 65 oocytes (55.4%) developed to the 2-cell stage. All the 2-cell embryos were transferred to the oviducts of pseudopregnant recipients and 23 young (63.9%, 23/36) were born. All of young analyzed carried the transgene and showed the luciferase gene expression. PMID- 1451766 TI - [Genetic profile of LIBP/1 inbred strain derived from the Kunming outbred stock of the mouse]. AB - To make the genetic profile of the LIBP/1 inbred strain obtained from Kunming mice, the most widely used outbred stock in China, 26 loci were examined. The genotypes of four kinds of coat color genes were a/a, B/B, c/c and D/D. The results of testing 21 biochemical marker genes showed Akp-1b, Amy-1a, Car-2a, Ce 2a, Es-1b, Es-3a, Es-10a, Es-11a, Gpd-1a, Gpi-1a, Gus-1b, Hbbs, Idh-1a, Ldr-1a, Mod-1a, Mup-1b, Pep-3b, Pgm-a, Sep-1b, Tam-1c, and Trfb. The H-2 gene loci were Kb and Db. PMID- 1451767 TI - [Developmental study of the ventral scent gland of the Mongolian gerbil]. AB - Male and female in bred Mongolian gerbils aged 4, 5, 10, and 20 weeks were examined for the presence of a ventral scent gland macroscopically and histologically. It was found in about half of the gerbils aged 4 weeks and in all of the gerbils aged over 5 weeks. In adult male gerbils it weighed three times as much as in females. The ventral scent gland exhibited a sebaceous-like structure which consists of giant glandular cells with small vacuoles in the cytoplasm and the glandular cells displayed eosinophilic bodies contained within a duct, which are extruded through the lumen as holocrine-type secretion. PMID- 1451768 TI - The California Family Health Project. PMID- 1451769 TI - Navigating treatment impasses at the disclosure of incest: combining ideas from feminism and social constructionism. AB - This article describes an approach to the social and emotional schisms that characterize the disclosure of intrafamilial sexual abuse (incest). It argues that ideas from social constructionism and feminism can be combined in such a way that what appear as either/or choices become both--and possibilities. These include: social control versus therapy, shame versus pride, attachment to one's abusive partner versus attachment to one's injured child, and "justice" versus "care." PMID- 1451770 TI - Transformations: a blueprint for narrative changes in therapy. AB - When problematic-symptomatic behaviors are conceived as embedded, retained, and maintained in collective stories, therapy can be described as the transformative process by which patients, families, and therapists co-generate qualitative changes in those stories. An emphasis on narratives allows one to specify further how those transformations unfold at the more "micro" level of the exchanges that take place throughout the consultation. To that specification is devoted the core of this essay, which closes with a discussion of the clinical, training, and, especially, research potentials of this systematization. PMID- 1451771 TI - The California Family Health Project: I. Introduction and a description of adult health. AB - Little research has addressed patterns of family and health relationships that reflect both the scope and complexity of family life and the breadth and diversity of health. In the first of a series of articles, we describe the California Family Health Project, a study in which four large "domains" of family life (Structure/Organization, World View, Problem Solving, and Emotional Management) were mapped, described, and compared with a large battery of adult health measures. We first present a brief critical overview of the literature on family and health research, then explain our rationale, define our approach to the multivariate analysis of family and health data, and describe our sample of 225 community-based families. To prepare for analyses with the family variables, we next present descriptive data based on separate principal components analysis (PCA) and multidimensional scaling analysis (MDS) of 14 self-reported health scores for husbands and for wives. No grouping or clustering of health variables emerged for either husbands or wives in the PCAs. A two-dimensional MDS analysis for husbands and for wives displayed the health variables in a circular pattern in which no predominant descriptive dimension or group of discrete dimensions emerged. Consequently, we decided that all 14 health scores will be used in the analyses, with the family variables to follow. PMID- 1451772 TI - The California Family Health Project: II. Family world view and adult health. AB - This article explores the pattern of relationships between family World View and adult Health in a community-based sample of 225 families. Family World View refers to the beliefs, appraisals, and values that define a family's orientation to the world. The interrelationships among eight self-reported family World View variables are described, using principal components analyses (PCA) and multidimensional scaling analyses (MDS). Derived, joint-spouse World Views also are examined using inter-battery factor analysis. The World View variables then are analyzed as a set with 14 self-reported health variables for husbands and wives separately, using canonical correlation. The PCAs for family World View yielded poor solutions for both husbands and wives. The MDS displayed the eight variables in a circular pattern for husbands and for wives, indicating the absence of a single broad dimension, or subgroupings of separate dimensions, that could be used to "describe" the domain. In the canonical analyses, family World View was a strong correlate of Health, with approximately 50% of the variance accounted for by the respective canonical variates. For husbands, what we called Family Coherence, Family Religiousness, Family Life Engagement, and Family Optimism, were correlated with Health. For wives, Family Coherence, Family Religiousness, and Family Optimism, were correlated with Health. Different patterns of health scores emerged by gender, with behavioral indicators, such as Smoking and Drinking, more salient for husbands, and mood indicators, such as Anxiety and Depression, more salient for wives. PMID- 1451773 TI - The California Family Health Project: III. Family emotion management and adult health. AB - This article explores the broad patterning of interrelationships between family Emotion Management and adult Health in a community-based sample of 225 families. Emotion Management refers to how emotion is expressed, acknowledged, and managed by the marital partners. Fifteen reliable-observer ratings of husband-wife behavior were made during each of three 10-minute Emotion Management Interaction Tasks (EMITs). Each of the three tasks "pulled" for the expression of a different emotional theme: loss, intimacy, or conflict. A principle components analysis of the 15 ratings yielded a poor solution. A nonmetric, multidimensional scaling analysis described a two-dimensional, bipolar display with ordering among the variables in each of two wings. One dimension reflected positive versus negative Emotion Management characteristics, and the second reflected active and overt versus passive or covert emotional expression. The pattern of relationships among the couple ratings was similar for each of the three tasks. Using canonical correlation, the couple ratings demonstrated significant associations with 14 adult Health scores for both husbands and wives for the intimacy and conflict tasks, but not for the loss task. Specific gender patterns also emerged. In general, couple overt emotional aversiveness was negatively associated with husbands' health, and couple emotional avoidance/distance was negatively associated with wives' health. PMID- 1451774 TI - From front line to home front: a study of secondary traumatization. AB - While the long-term effects of combat trauma on veterans have been studied extensively, its impact on veterans' wives has yet to be investigated. This study examined the implications of combat-induced psychopathology--wartime combat stress reaction (CSR) and current posttraumatic stress disorder (PTSD)--in a sample of 205 wives of Israeli combat veterans of the 1982 Lebanon war. Results show that both CSR and PTSD were associated with increased psychiatric symptoms in the wives. In addition, current PTSD was particularly found to contribute to impaired social relations among veterans' wives in a broad range of contexts, from inner feelings of loneliness, through impaired marital and family relations, and extending to the wider social network. Implications of these findings for treatment and further research are discussed. PMID- 1451775 TI - Behavioral problems in sons of incarcerated or otherwise absent fathers: the issue of separation. AB - The decade of the 1980s witnessed more than a doubling in the number of incarcerated individuals. Little is known about the psychological reactions of children whose parents are incarcerated, although a variety of behavioral disorders apparently related to separation, stigma, and deception of the child has been reported. The possibility of aggressive or antisocial behavior emerging in sons of incarcerated fathers has been mentioned as of particular concern in some reports. This article discusses salient themes in the literature on the reactions of children to parental incarceration, with an emphasis on boys' reactions to incarceration of their fathers. It critiques this literature and compares the findings with literature on the effects of separation in father absence related to other causes (for example, divorce, death, military service). Behavioral or emotional disorder associated with paternal incarceration probably is related mainly to associated factors such as the meaning of the incarceration to the child, the remaining caretaker's psychological characteristics and psychopathology, the parenting relationship between the caretaker and the child, and the coping capacities and resources of the family, rather than to the separation itself. Recommendations for further research in this increasingly important field are provided. PMID- 1451776 TI - Purification, inhibitory properties and amino acid sequence of a new serine proteinase inhibitor from white mustard (Sinapis alba L.) seed. AB - A new serine proteinase inhibitor, mustard trypsin inhibitor 2 (MTI-2), has been isolated from white mustard (Sinapis alba L.) seed by affinity chromatography and reverse phase HPLC. The protein inhibits the catalytic activity of bovine beta trypsin and bovine alpha-chymotrypsin, with dissociation constants (Kd) of 1.6 x 10(-10) M and 5.0 x 10(-7) M, respectively, at pH 8.0 and 21 degrees C, the stoichiometry of both proteinase-inhibitor complexes being 1:1. The amino acid sequence of MTI-2, which was determined following S-pyridylethylation, is comprised of 63 residues, corresponding to a molecular weight of about 7 kDa, and shows only extremely limited homology to other serine proteinase inhibitors. PMID- 1451777 TI - Effects of okadaic acid on the activities of two distinct phosphatidate phosphohydrolases in rat hepatocytes. AB - Incubation of hepatocytes with okadaic acid displaced the N-ethylmaleimide sensitive phosphatidate phosphohydrolase from the membrane fraction into the cytosol and partially prevented the oleate-induced movement of phosphohydrolase from cytosol to membranes. However, higher concentrations of oleate still caused translocation and activation of the phosphohydrolase. This enzyme is stimulated by Mg2+, and is probably involved in glycerolipid synthesis. Okadaic acid also decreased the concentration of diacylglycerol within the hepatocytes. Okadiac acid had no observable effect on the activity of an N-ethylmaleimide-insensitive phosphatidate phosphohydrolase which remained firmly attached to membranes. This activity is not stimulated by Mg2+ and is probably involved in signal transduction by the phospholipase D pathway. PMID- 1451778 TI - Phorbol ester-induced secretion of human hepatocyte growth factor by human skin fibroblasts and its inhibition by dexamethasone. AB - Human skin fibroblasts secreted a certain amount of human hepatocyte growth factor (hHGF), as determined by an enzyme-linked immunosorbent assay for hHGF. This hHGF secretion was remarkably stimulated by protein kinase C (PKC) activating phorbol esters, which was inhibited by the simultaneous addition of dexamethasone. Pretreatment with phorbol 12-myristate 13-acetate (PMA) caused a down-regulation in hHGF secretion. hHGF secreted by the PMA-treated cells showed a potent hepatocyte growth-promoting activity which was neutralized by an anti hHGF antiserum. These results indicate both that PMA-treated human skin fibroblasts produce biologically active hHGF and the possible involvement of PKC activation in this process. PMID- 1451779 TI - The consensus sequences for cdc2 kinase and for casein kinase-2 are mutually incompatible. A study with peptides derived from the beta-subunit of casein kinase-2. AB - Two series of synthetic peptides that reproduce the amino- and carboxyl-terminal segments of the beta-subunit of casein kinase-2, including the sites phosphorylated by CK2 and cdc2 kinase, respectively, have been used as model substrates for these enzymes. The N-terminal peptide beta(1-9), MSSSEEVSW, is readily phosphorylated by CK2 but not all by cdc2. The opposite is true of the C terminal peptide beta(206-215), NFKSPVKTIR, whose Ser-4 is a good target for cdc2 while being unaffected by CK2. The individual substitutions of Pro-5 and Lys-7 in the latter peptide with Gly and Ala (or Glu), respectively, prevent its phosphorylation by cdc2, whereas the substitution of Lys-3 with Ala is well tolerated and the substitution of the target Ser with Thr actually improves phosphorylation. Thus the consensus sequence for cdc2 is shown to be X-S-P-X-K. Such a requirement for a basic residue at position +3 is opposite to that of CK2 whose consensus sequence (S-X-X-E/D/Yp/Sp) includes an acidic residue at the same position. Moreover the motif Ser-Pro is detrimental for CK2, preventing the phosphorylation of otherwise suitable peptides. These observations would rule out the possibility that the site specificity of CK2 might overlap with that of cdc2 and possibly of other Pro-directed protein kinases. PMID- 1451780 TI - Unimpaired effect of insulin on glucokinase gene expression in hepatocytes challenged with amylin. AB - Amylin appears to interfere with the action of insulin in muscle and possibly in liver. We have attempted to detect a direct antagonism between amylin and insulin in cultured rat hepatocytes. The stimulation of glucokinase gene expression was used as a marker of insulin action. Amylin proved ineffective in suppressing subsequent accumulation of glucokinase mRNA in response to maximal or submaximal doses of insulin. When applied to cells already induced by prior incubation with insulin alone, amylin failed to reverse induction, in contrast to the effectiveness of glucagon under the same conditions. Thus, amylin is not a physiological antagonist of insulin in the control of hepatic glucokinase gene expression. PMID- 1451781 TI - Rapid kinetics of the interaction between daunomycin and drug-sensitive or drug resistant P388 leukemia cells. AB - The initial stages of the interaction of daunomycin (DNM) with drug-sensitive (P388/S) and drug-resistant (P388/100) cells have been defined by a rapid kinetics stopped-flow procedure. The process can be described by two kinetic components. The faster component accounts for rapid occupation of cell surface sites by DNM, as supported by experiments with liposomes with different surface charge. On the other hand, the effect of verapamil in the assays, suggests that the slower component is involved in the transport of the drug into the cells. Our observations are consistent with a loss in the control of the passive permeability to the drugs in the drug-resistant tumor cells. PMID- 1451782 TI - Molecular cloning of three cDNAs that encode cysteine proteinases in the digestive gland of the American lobster (Homarus americanus). PMID- 1451783 TI - A gene family homologous to the S-phase specific gene in higher plants is essential for cell proliferation in Saccharomyces cerevisiae. AB - Previously we reported the isolation and characterization of the gene, cyc07, which was specifically expressed in the S phase during the cell cycle in synchronous cell division cultures of the higher plant, Catharanthus roseus. We found that the yeast Saccharomyces cerevisiae contains two closely related genes which show a high degree of similarity (about 64% at the amino acid level) to cyc07 of C. roseus. Site-directed disruption mutations demonstrated that the two yeast genes, homologous to cyc07, constitute an essential gene family for cell proliferation in yeast cells. Furthermore, the rate of cell proliferation varied with the gene copy number. PMID- 1451784 TI - A dysfunctional C1 inhibitor protein with a new reactive center mutation (Arg-444 ->Leu). AB - A P1 mutation (Arg-444-->Leu) was identified in a dysfunctional C1 inhibitor from a patient with type 2 hereditary angioneurotic edema. The mutation was defined at the level of the protein (by sequence analysis of the Pseudomonas aeruginosa elastase-derived reactive center peptide), and the mRNA (CGC-->CTC) (by sequence analysis of PCR-amplified DNA). PMID- 1451785 TI - Pine stilbene synthase cDNA, a tool for probing environmental stress. AB - Stilbene synthase cDNAs were isolated from a pine (Pinus sylvestris) cDNA library. Poly(A)+RNA required for the preparation was obtained from young seedlings challenged with Botrytis cinerea. A full-length cDNA encoding pinosylvin-forming stilbene synthase was sequenced, and the deduced amino acid sequence was compared with sequences of resveratrol-forming stilbene synthases. The cDNA coding for the key enzyme of pinosylvin formation is a valuable tool for detecting early effects of environmental stress in pine needles. PMID- 1451786 TI - Cloning and characterization of the rat glutathione peroxidase gene. AB - The increased activity of glutathione peroxidase (GSHPx) in rat lungs is associated with the development of tolerance of the animals to hyperoxia. To understand further the regulation of expression of this enzyme, the molecular structure of the corresponding rat gene was characterized. The rat GSHPx gene consists of two exons interrupted by a single intron of 217 base pairs. The same initiation sites for transcription were found to be utilized in both lung and liver. The promoter of the GSHPx gene contains neither a 'TATA' box nor a 'CAAT' box. Instead, it comprises two copies of Sp1 binding motif and one copy of AP-2 binding motif. These features of the promoter may offer a clue to the mechanisms by which the expression of this gene is controlled. PMID- 1451787 TI - Rainbow trout cytochrome P-450c17 (17 alpha-hydroxylase/17,20-lyase). cDNA cloning, enzymatic properties and temporal pattern of ovarian P-450c17 mRNA expression during oogenesis. AB - A cDNA clone encoding cytochrome P-450c17 (17 alpha-hydroxylase/17,20-lyase) was isolated from a rainbow trout ovarian follicle cDNA library. The cDNA contained an open reading frame of 1,542 nucleotides encoding a protein of 514 amino acid residues. The amino acid sequence of trout P-450c17 shows a much greater homology with chicken P-450c17 than with that of human, bovine and rat. The trout P-450c17 expressed in non-steroidogenic mammalian COS-1 cells showed both 17 alpha hydroxylase and 17,20-lyase activities. The cDNA only hybridized to a single species of mRNA (2.4 kb) isolated from rainbow trout ovaries; the 2.4 kb transcripts were abundant in trout ovaries during the later stages of oogenesis. PMID- 1451788 TI - cDNA cloning of rat proteasome subunit RC1, a homologue of RING10 located in the human MHC class II region. AB - The nucleotide sequence of a cDNA that encodes a new subunit, named RCl, of rat proteasomes (multicatalytic proteinase complexes) has been determined. The polypeptide predicted from the open reading frame consisted of 208 amino acid residues with a calculated molecular mass of 23, 130, which is consistent with the size obtained by electrophoretic analysis of purified RCl. The partial amino acid sequences of several fragments of RCl, obtained by protein chemical analyses, were found to be in excellent accordance with those deduced from the cDNA sequence. Surprisingly, the overall structure of RCl was found to be almost identical to that of recently isolated RING10, whose gene is located in the class II region of the human MHC gene cluster. This finding suggests that RCl is a homologue of human RING10, supporting the proposal that proteasomes are involved in the antigen processing pathway. PMID- 1451789 TI - Development of insulin sensitivity in rat skeletal muscle. Studies of glucose transporter and insulin receptor mRNA levels. AB - Expression of GLUT-4 and insulin receptor mRNAs was investigated in rat skeletal muscle by Northern hybridization. GLUT-4 mRNA was barely detectable in foetal muscle, was expressed at low levels by 1-8 days and at 2-3-fold higher levels during and after weaning (18-40 days). In contrast there was little change in insulin receptor mRNA levels prior to weaning and a reduction in mRNA abundance between 18 and 40 days. Weaning rats on to a diet rich in fat prevented the increase in GLUT-4 abundance seen between 15 and 29 days in animals weaned on a high-carbohydrate diet. PMID- 1451790 TI - Expression of 9 Salmonella typhimurium enzymes for cobinamide synthesis. Identification of the 11-methyl and 20-methyl transferases of corrin biosynthesis. AB - Nine of the cbi genes from the 17.5 kb cob operon of Salmonella typhimurium previously shown by genetic studies to be involved in the biosynthesis of cobinamide from precorrin-2, have been subcloned and expressed in Escherichia coli. Seven of the gene products were found in the soluble fraction of cell lysates and have been purified. The gene products corresponding to cbi E, F, H and L were shown by SAM binding and by homology with other SAM-binding proteins to be candidates for the methyltransferases of vitamin B12 biosynthesis. The enzymatic functions of the gene products of cbiL and cbiF are associated with C methylation at C-20 of precorrin-2 and C-11 of precorrin-3. PMID- 1451791 TI - A consensus repeat sequence from the human insulin gene linked polymorphic region adopts multiple quadriplex DNA structures in vitro. AB - A hypervariable region consisting of repeats of a 14 base pair (bp) consensus sequence ACAGGGGT(G/C)(T/C)GGGG is located 363 bp upstream of the human insulin gene. Different repeat numbers of this oligonucleotide give rise to a polymorphism, and so this region is commonly known as the insulin gene linked polymorphic region (ILPR). Here we present evidence, based on the mobility in non denaturing polyacrylamide gels of two dissimilarly sized oligonucleotides containing the ILPR consensus sequence, that this sequence can adopt a number of quadriplex DNA structures in vitro. PMID- 1451793 TI - Expansion of the mammalian 3 beta-hydroxysteroid dehydrogenase/plant dihydroflavonol reductase superfamily to include a bacterial cholesterol dehydrogenase, a bacterial UDP-galactose-4-epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus. AB - Mammalian 3 beta-hydroxysteroid dehydrogenase and plant dihydroflavonol reductases are descended from a common ancestor. Here we present evidence that Nocardia cholesterol dehydrogenase, E. coli UDP-galactose-4 epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus are homologous to 3 beta-hydroxysteroid dehydrogenase and dihydroflavonol reductase. Analysis of a multiple alignment of these sequences indicates that viral ORFs are most closely related to the mammalian 3 beta-hydroxysteroid dehydrogenases. The ancestral protein of this superfamily is likely to be one that metabolized sugar nucleotides. The sequence similarity between 3 beta-hydroxysteroid dehydrogenase and the viral ORFs is sufficient to suggest that these ORFs have an activity that is similar to 3 beta-hydroxysteroid dehydrogenase or cholesterol dehydrogenase, although the putative substrates are not yet known. PMID- 1451792 TI - Cloning and sequence analysis of the phenylalanyl-tRNA synthetase genes (pheST) from Thermus thermophilus. AB - While crystals suitable for X-ray diffraction analyses are available of phenylalanyl-tRNA synthetase (PheRS) from the thermophilic bacterium Thermus thermophilus, neither the primary structure of its constituent alpha and beta subunits nor the nucleotide sequence of the corresponding pheS and pheT genes were known. Using specific oligonucleotides of conserved pheS regions that were adapted to the T. thermophilus codon usage, we identified, cloned and subsequently sequenced the pheST genes of this bacterium. The sequences reported here will greatly aid in the three-dimensional structure determination of T. thermophilus PheRS, a heterotetrameric (alpha 2 beta 2), class II aminoacyl-tRNA synthetase. PMID- 1451794 TI - Stimulation of glucose transport in L6 muscle cells by long-term intermittent stretch-relaxation. AB - Skeletal muscle stretch increases resting metabolism and causes hypertrophy. We have examined the effect of mechanical stretch in vitro on glucose transport activity and transporter contents in L6 muscle cells. Long-term (24-48 h) stretch relaxation (25% maximal elongation at 30 cycles per min) of cell monolayers significantly increased glucose uptake by 1.6- to 2-fold in myotubes but not in myoblasts. The presence of serum was required for the stretch-relaxation induced increase in glucose uptake. Cycloheximide inhibited the mechanical stimulation of glucose uptake, and the latter response was not additive to the stimulatory effect of long-term exposure to insulin. GLUT1 and GLUT4 glucose transporter contents were not changed in total cell membranes from mechanically stimulated cells relative to controls. These results indicate that mechanical stimulation through passive stretch may be an important regulation of nutrient uptake in fetal myotubes independent of innervation. PMID- 1451795 TI - Glycation of crystallins in lenses from aging and diabetic individuals. AB - Water-soluble crystallins were obtained from clear human lenses of different age (4-81-year-olds) and lenses of individuals showing senile or diabetic cataracts. Levels of early glycation products were high in the high molecular weight material (HM) and the alpha-crystallin fractions, compared with beta- and gamma crystallins. This difference becomes more prominent upon aging. The content of total early glycation products in HM and alpha-crystallin increases clearly with age, whereas levels remain relatively constant in the beta- and gamma crystallins. There is an elevation of early products in cataractous lenses from diabetic individuals compared with those suffering from senile cataract. Specific non-tryptophan fluorescence (excitation/emission wavelengths 370/440 nm), used as an indicator for late glycation products, increased dramatically with age and was 2-fold higher in the diabetic subjects. Levels of fluorescence decreased in the order HM > alpha- > beta- > gamma-crystallins. The results suggest an increase in glycation rate in alpha-crystallin as a result of aging and diabetes, while the rate of glycation of beta- and gamma-crystallins remains almost constant. PMID- 1451796 TI - Structure of UvrABC excinuclease-UV-damaged DNA complexes studied by flow linear dichroism. DNA curved by UvrB and UvrC. AB - The interaction between UvrABC excinuclease from Escherichia coli and ultraviolet light-(UV) damaged DNA was studied by flow linear dichroism. The dichroism signal from DNA was drastically decreased in intensity upon incubation with UvrA and UvrB or whole enzyme in the presence of effector ATP. The change was specific for UV-damaged DNA, and a concluded suppressed DNA orientation suggests the wrapping of DNA around the protein. The incubation with the UvrC subunit alone also somewhat reduces the signal, however, in this case the change was smaller and not specific for UV-damaged DNA. The structural modification of DNA, promoted by the (UvrA2-UvrB) complex, probably facilitates or stabilizes the interaction of the UvrC subunit with DNA for the excision. PMID- 1451797 TI - Correlation of cofactor binding and the quaternary structure of pyruvate decarboxylase as revealed by 31P NMR spectroscopy. AB - The pH dependence of the quaternary structure of pyruvate decarboxylase (EC 4.1.1.1) has recently been discovered [(1990) FEBS Lett. 266, 17-20; (1992) Biochemistry (in press)]. In the present study we have investigated the change in quaternary structure by observing the binding of the cofactor, thiamine pyrophosphate, using 31P NMR spectroscopy. The dissociation of the native tetramers into dimers when increasing the pH coincides with a weaker binding of the cofactor and loss of enzyme activity. The results provide further evidence that thiamine pyrophosphate is bound primarily via the beta-phosphate moiety. In addition, a phosphoserine has been discovered in two of the four subunits. PMID- 1451798 TI - Initiator-promoter coupling of phospholipases D and A2 in platelets upon cholesterol incorporation. AB - Since phospholipases exist within a membrane lipid environment, it is not unreasonable to assume that cholesterol capable of changing the lipid environment can effect the coupling relationship among the signal transducing components. Our previous study showed that the 'molecular switch' through which membrane cholesterol modulates cyclic nucleotide levels and Na+/H+ exchange within human platelets is phospholipase A2. We demonstrate here that membrane cholesterol initiates the activation of phosphatidyl choline phospholipase D and phosphatidic acid thus generated promotes the activation of its phospholipase A2 in the presence of extraplatelet calcium. More important, inhibition of phospholipase D by zinc blocks the activation of phosphatidic acid phospholipase A2 in platelets upon cholesterol incorporation. Our result led us to postulate that membrane cholesterol induced initiation promotion coupling of phospholipases D and A2 in human platelets may be responsible for the hypersensitized state of platelets in hypercholesterolemic patients. PMID- 1451799 TI - Na(+)-dependent AIB transport by neuroblastoma cells. AB - Na(+)-dependent amino isobutyric acid transport by two neuroblastoma cell lines with and without amplification of the oncogene N-myc is studied. Surprisingly, the contribution of system A is greater in the cell line showing no N-myc amplification. Preliminary data support a role for essential tyrosine and cysteine residues in the active center of the carriers, mainly in system A. PMID- 1451800 TI - Human peripheral blood lymphocytes express D5 dopamine receptor gene and transcribe the two pseudogenes. AB - Sequential reverse transcription and polymerase chain reaction (RT-PCR) of the mRNA were used to investigate the expression of dopamine receptors in human peripheral blood lymphocytes. The RT-PCR products contained three types of sequences, each corresponding to those of the D5 dopamine receptor gene and the two related pseudogenes. The lymphocyte cDNA library also contained the clones encoding parts of the three genes. Binding profiles of dopaminergic ligands to the lymphocytes were similar to those for the native neuronal membranes. PMID- 1451801 TI - Interaction of alpha subunit of GTP-binding protein Go with a 20-kDa Triton insoluble membrane protein in bovine brain. AB - Heterotrimeric Go bound to the membranes of bovine brain, but Go alpha remained bound to the membranes even after activation with GTP gamma S. Furthermore, Go alpha bound to a Triton X-100-insoluble fraction of the membranes in a saturable manner. However, the 37-kDa Go alpha eliminated by trypsin at the amino-terminus could not bind to the fraction. Using a blot overlay approach of the Triton insoluble fraction, only a 20-kDa protein was identified that interacts with Go alpha. These results indicate that Go alpha binds to a 20-kDa Triton-insoluble protein in the bovine brain membranes. PMID- 1451802 TI - The influence of oligodeoxyribonucleotide phosphorothioate pyrimidine strands on triplex formation. AB - Analogues of the homopyrimidine oligonucleotide dT15 that contained phosphorothioate bonds of a mixture of diastereoisomers or one of the two stereoisomers (either Rp or Sp) were synthesized. The analogues were mixed under conditions conducive to the formation of triple-stranded assemblies. The mixtures were characterized by their thermal stabilities (Tm values), CD spectra, and gel electrophoresis pattern. The 34-mer duplexes containing 15 central purines on one strand and 15 complementary pyrimidines on the other strand gave no detectable triple helix upon combination with dT15S14. On the other hand, 34-bp duplexes with dT15S1, having Rp or Sp, formed triple helixes. This suggests that a steric factor plays an important role in triple helix formation. PMID- 1451803 TI - A GC box in the bidirectional promoter is essential for expression of the human dihydrofolate reductase and mismatch repair protein 1 genes. AB - The human dihydrofolate reductase and mismatch repair protein 1 genes are organized in a head-to-head configuration separated by an 88 base-pair segment and directed by a bidirectional promoter. In vivo transient assays of the site directed mutant promoters using firefly luciferase as a reporter showed that an AT-rich sequence, ACAAATA, in the GC-rich promoter sequence is not required for transcription. However, two out of four GC boxes were shown to function as bidirectional positive regulatory elements. Among them, a GC box at the midpoint of the region between the two initiation sites is essential for supporting minimal bidirectional activity. PMID- 1451804 TI - Comparison of the Ca2+ binding properties of the gamma-carboxyglutamic acid containing module of protein Z in the intact protein and in N-terminal fragments. AB - Protein Z is a vitamin K-dependent plasma protein of unknown function. Its modular structure is identical with those of factors VII, IX, X, and protein C. These proteins have an N-terminal gamma-carboxyglutamic acid (Gla)-containing module which binds six to ten Ca2+. In factors IX, X, and protein C, the adjacent epidermal growth factor (EGF)-like module binds one Ca2+ whereas the EGF-like module in protein Z does not. We have compared the Ca2+ binding properties of a fragment of protein Z comprising the Gla and N-terminal EGF-like modules (pZ GlaEGFN) with those of intact protein Z and the isolated Gla module by measuring the Ca(2+)-induced quenching of the intrinsic protein fluorescence. The similar Ca2+ affinities of pZ-GlaEGFN and protein Z indicate that pZ-GlaEGFN has a native conformation and normal Ca2+ binding properties. A comparison of the Ca2+ binding to pZ-GlaEGFN with those to the corresponding fragments of factors IX, X, and protein C indicate that Ca2+ binding to the N-terminal EGF-like modules in the latter proteins does not influence the folding and Ca2+ binding properties of their Gla modules. Furthermore, the Ca(2+)-induced fluorescence enhancements of GlaEGF fragments from factors IX, X, and protein C appear to be caused by Ca2+ binding to the site in the EGF-like modules since it is not observed for pZ GlaEGFN. PMID- 1451806 TI - Complex formation between glutamyl-tRNA synthetase and glutamyl-tRNA reductase during the tRNA-dependent synthesis of 5-aminolevulinic acid in Chlamydomonas reinhardtii. AB - The formation of a stable complex between glutamyl-tRNA synthetase and the first enzyme of chlorophyll biosynthesis glutamyl-tRNA reductase was investigated in the green alga Chlamydomonas reinhardtii. Apparently homogenous enzymes, purified after previously established purification protocols were incubated in various combinations with ATP, glutamate, tRNA(Glu) and NADPH and formed complexes were isolated via glycerol gradient centrifugation. Stable complexes were detected only after the preincubation of glutamyl-tRNA synthetase, glutamyl-tRNA reductase with either glutamyl-tRNA or free tRNA(Glu), ATP and glutamate, indicating the obligatory requirement of aminoacylated tRNA(Glu) for complex formation. The further addition of NADPH resulting in the reduction of the tRNA-bound glutamate to glutamate 1-semialdehyde led to the dissociation of the complex. Once complexed to the two enzymes tRNA(Glu) was found to be partially protected from ribonuclease digestion. Escherichia coli, Bacillus subtilis and Synechocystis 6803 tRNA(Glu) were efficiently incorporated into the protein-RNA complex. The detected complexes provide the chloroplast with a potential channeling mechanism for Glu-tRNA(Glu) into chlorophyll synthesis in order to compete with the chloroplastic protein synthesis machinery. PMID- 1451805 TI - Characterization of a spinach psbS cDNA encoding the 22 kDa protein of photosystem II. AB - An intrinsic 22 kDa polypeptide is found associated with the oxygen-evolving photosystem II (PSII) core complex in all green plants and cyanobacteria so far examined, although it does not appear to be required for oxygen evolution. Amino acid sequence information obtained from the purified 22 kDa protein was used to construct a probe that was employed to isolate a full-length cDNA clone encoding the 274-residue precursor of the 22 kDa protein. Hydropathy plot analysis predicts the existence of four membrane-spanning helices in the mature protein. The two halves of the approximately 200-residue mature protein show high sequence similarity to each other, suggesting that the psbS gene arose from an internal gene duplication. The 22 kDa protein has some sequence similarity to chlorophyll a/b-binding proteins. PMID- 1451807 TI - Natural human tumor necrosis factor beta (lymphotoxin). Variable O-glycosylation at Thr7, proteolytic processing, and allelic variation. AB - Natural human tumor necrosis factor beta (TNF-beta) purified from supernatants of a human B-lymphoblastoid cell line was found to be heterogeneous in molecular mass, with seven components resolved by gel electrophoresis. All components are N glycosylated at Asn62; N-glycosylation does not contribute to heterogeneity. In addition, part of the molecules are O-glycosylated at Thr7; O-glycosylation is heterogeneous due to variable decoration with neuraminic acid. The four lower molecular mass forms are derived from the full-length protein by trypsin-like proteolytic cleavage in the N-proximal region; these clipped molecules lack O linked carbohydrates. Two allelic variants differing in amino acid position 26 (threonine/asparagine) were identified. PMID- 1451808 TI - 'All-or-none' mechanism of the molten globule unfolding. AB - The Gdm-HCl-induced unfolding of bovine carbonic anhydrase B and S. aureus beta lactamase was studied at 4 degrees C by a variety of methods. With the use of FPLC it has been shown that within the transition from the molten globule to the unfolded state the distribution function of molecular dimensions is bimodal. This means that equilibrium intermediates between the molten globule and the unfolded states are absent, i.e. the molten globule unfolding follows the 'all-or-none' mechanism. PMID- 1451809 TI - Clinical and therapeutic ambiguities in patients suffering from claudication due to atheromatous disease of the lower limbs. PMID- 1451810 TI - Endarterectomy: a brief look into the past and perspectives for the future. PMID- 1451811 TI - Vessel repair after balloon angioplasty: morphological appearance and prostacyclin synthesising capacity. AB - Immediately after balloon dilatation of the rabbit aorta the release of prostacyclin is diminished. In this study the morphological appearance and time course for recovery of prostacyclin production after balloon dilatation have been investigated. Healthy rabbit aortas were analysed 1 h (n = 12), 1 week (n = 13) and 1 month (n = 13) after angioplasty. The production of prostacyclin, from dilated and non-dilated aortic segments, was recorded in a perfusion system. Prostacyclin was measured as its stable degradation product 6-keto-PGF1 alpha. Scanning electron microscopy and light microscopy were used to analyse the type of cells present at the luminal surfaces of the segments. When endothelial cells were found their degree of coverage was also estimated. One hour after balloon dilatation there was a lower production of prostacyclin from the angioplasty segments than from controls. Also, the response to added arachidonic acid (AA) was lower in the angioplasty segments. No endothelial cells were present in the angioplasty segments. After 1 week there was no difference in the basic production of prostacyclin but there was still a lower response from angioplasty segments to the addition of AA. The inner surfaces of the angioplasty segments were covered by three to five layers of smooth muscle cells (SMC). After 1 month, there was no difference in either the basic production or after the addition of AA between control and angioplasty segments. The angioplasty segments were covered with a multilayer of SMC. The control segments had an almost complete cover of endothelial cells at every time interval after angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451812 TI - Management of acute arterial trauma of the upper extremity. AB - During a 3.5 year period ending in September 1991, 50 patients with 51 arterial injuries of the upper extremity were operated on and followed up for more than 6 months. The majority of the cases suffered penetrating injuries, but in 18% blunt trauma led to thrombosis. The most frequently observed signs were haemorrhage, neurological disorders and a peripheral pulse deficit. The brachial artery was most frequently injured. Preoperative arteriography was performed in 20% and peroperative angiography in 16% of cases. Reconstructive surgery was performed in 88% and the brachial artery was ligated in a single patient who was in shock. An end to end anastomosis was possible in 55% and in 45% of cases an autogenous vein graft was used. A microsurgical technique was used in cases of forearm arterial injuries. In five patients with prolonged ischaemia, forearm fasciotomies were needed. Additional procedures such as venous, bone or nerve repair was also necessary. In four cases a temporary shunt was used. All patients were alive with late patency of 91% in the axillobrachial arterial segment. A single failure after repeated brachial artery reconstruction was observed following severe traumatic amputation with large tissue defects. Post-operative arteriography revealed a good anastomosis with patent grafts. Arterial reconstruction is clearly necessary in these injuries and we believe that an experienced vascular surgeon should be involved. PMID- 1451813 TI - Amputation level is not adversely affected by previous femorodistal bypass surgery. AB - Data was reviewed on patients presenting with lower limb-threatening ischaemia to a single vascular unit between September 1984 and December 1990. Three hundred and thirty patients underwent either femoro-popliteal or femoro-infrapopliteal reconstructive surgery and 316 primary amputations were performed on 281 patients. Sixty-three secondary amputations were performed following a femoro distal bypass failure. The below-knee amputation to above-knee amputation ratio (BKA/AKA) was 1.0 in the primary amputation group to 0.91 in the secondary amputation group. A direct comparison cannot be made as the patients represent two separate clinical groups. The ratio of reconstructive operations to primary amputations more than doubled between the first and second halves of the study. The BKA:AKA ratio in the secondary amputation group and the total number of secondary amputations remained relatively constant. This study supports the view that previous femoro-distal surgery does not adversely affect the overall outcome of amputation. PMID- 1451814 TI - The potential risk for subclavian vein occlusion in patients on haemodialysis. AB - Subclavian vein (SCV) stenosis or occlusion can be a late complication of temporary haemodialysis or following catheterisation for intravenous hyperalimentation. In five patients with prior catheterisation or trauma of the SCV, incapacitating oedema of the upper extremity developed only after the creation of ipsilateral arteriovenous (AV) fistulas for haemodialysis. The duration of the previous catheterisation was 2 to 4 weeks. Massive upper extremity oedema developed at 10 days to 22 months with an average of 11 months after the establishment of AV fistulas. Subclavian-axillary vein bypass using a ringed polytetrafluoroethylene graft was successful for one patient and ligation of the AV fistulae led to good results for the other three. In planning vascular access procedures in the upper extremity, venography should be mandatory to try to prevent such complications if a previous history of subclavian catheterisation exits. PMID- 1451815 TI - Femoropopliteal arterial reconstruction with intraoperative iliac transluminal angioplasty for disabling claudication: results of a combined approach. AB - Seventeen patients with disabling claudication resulting from multilevel arteriosclerotic disease were treated by combined intraoperative iliac transluminal angioplasty and femoropopliteal arterial reconstruction. Clinical improvement or total relief of ischaemic symptoms was observed in 15 out of 17 patients. Iliac pressure gradients were reduced with balloon dilatation to < 2 mmHg in all cases. The mean (+/- S.D.) resting ankle-brachial systolic pressure index increased from 0.42 +/- 0.14 to 0.87 +/- 0.21. Complications from intraoperative angioplasty were not encountered and no early graft failures were seen. The primary actuarial graft patency at 1, 2 and 5 years was 100, 88 and 67%, respectively. Combined intraoperative iliac transluminal angioplasty and femoropopliteal arterial reconstruction is a useful alternative to conventional surgical revascularisation in the treatment of selected patients with disabling claudication in the presence of multilevel arteriosclerotic disease. PMID- 1451816 TI - Peroperative anticoagulation with antithrombin or heparin in infrainguinal bypass surgery. AB - Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage. PMID- 1451817 TI - Infrarenal abdominal aortic aneurysms less than five centimetres in diameter: the surgeon's dilemma. AB - A number of recent studies have brought new data and a better understanding of the risk versus benefit of abdominal aortic aneurysm repair. The present evidence indicates that the risk of rupture for non tender aneurysms less than 5 cm is so low that patients can generally be followed by 6 monthly ultrasound and not undergo immediate operation. Surgery should be the method of choice for most patients where the aneurysm is greater than 5 cm. PMID- 1451818 TI - Popliteal vein entrapment in the normal population. AB - The aim of this study was to determine the incidence and severity of popliteal vein compression by full knee extension in the normal population. The popliteal veins in 100 healthy volunteers (200 limbs) with no history of previous deep vein thrombosis (DVT) or venous obstruction were examined using duplex scanning with the knee slightly flexed and then fully extended. Knee extension produced complete obstruction in 17 subjects and severe obstruction (< 50% decrease in diameter) in a further 10 subjects. Thirteen subjects had unilateral compression and 14 bilateral. The 27 subjects were tested for functional venous outflow obstruction with air plethysmography. In flexion, the outflow fraction was normal (> 40%) in all subjects. With the knee fully extended, severe or complete venous obstruction (outflow fraction < 10%) was found in eight subjects. Moderate obstruction (outflow fraction 10-40%) was found in all the remaining 19 subjects. When digital compression of the long saphenous vein was performed, these subjects also demonstrated severe outflow obstruction. Although the incidence of symptoms of functional venous obstruction is rare in the general population, these findings have important implications for venous stasis for patients on the operating table and in those having prolonged bed rest. Studies investigating the association between popliteal vein compression and postoperative deep venous thrombosis are needed. PMID- 1451819 TI - Adverse outcome in surgery for chronic leg ischaemia--risk factors and risk prediction when using different statistical methods. AB - OBJECTIVE: to compare two different statistical methods in predicting the outcome of surgery for chronic leg ischaemia. MATERIAL: the present study from the Swedvasc registry is based on an inception cohort of 1635 patients with chronic leg ischaemia (intermittent claudication in 609 and critical ischaemia in 1026 patients), who have been followed until 1 year after surgery. Outcome was classified as improved vs. not improved, amputated or dead in claudication and as the intact leg vs. amputation or death in critical ischaemia. METHODS: logistic regression analysis was compared to the inductive expert system program, Assistant Professional, in the prediction of outcome. Seventy per cent of cases in the data base were used to create a risk factor model including 17 variables registered in Swedvasc. These variables included an assessment of patients overall health status, severity of disease, the surgeon's experience and surgical procedures. This model was then evaluated using the remaining 30% of the patients in the data base. RESULTS: a risk score indicating a probability of an adverse outcome exceeding 0.5 was, in patients with intermittent claudication, associated with a sensitivity of 38% using logistic regression and 26% using Assistant Professional. The percentages of correctly predicted adverse outcomes were 29 and 50%, respectively. In patients with critical ischaemia, the sensitivities with the two methods were 68 and 38% and the predictive values 42 and 57%, respectively. CONCLUSIONS: the risk scores created with the two methods gave low sensitivities. It is concluded that risk functions could not be used to predict an adverse outcome in patients operated on for chronic leg ischaemia with the data set used. PMID- 1451820 TI - Growth factor release by smooth muscle cells is dependent on haemodynamic factors. AB - Abnormal proliferation of smooth muscle cells (SMCs) is a key event in the development of the atherosclerotic plaque. The early atherosclerotic plaque localises preferentially in areas of flow separation. The basic mechanisms which correlate haemodynamic forces and atherosclerotic plaque formation are not known. Bovine arterial SMCs were subjected to increasing levels of shear stress for 24 h in an in vitro system. The control group was subjected to similar incubation conditions without flow. SMCs subjected to shear stress released a higher quantity of mitogens, including a platelet derived growth factor (PDGF)-like substance. This mitogenic activity was partially reduced (30%, p < 0.01) by an excess of monospecific anti-PDGF antibody. The release of mitogens was proportional to the level of shear stress and was still evident 24 h after flow cessation. In conclusion, shear stress influences the release of mitogens; this might represent a mechanism which links haemodynamic forces and atherosclerotic plaque formation. PMID- 1451821 TI - Simultaneous resection of abdominal aortic aneurysms and early gastric cancer by retroperitoneal and transperitoneal approach. AB - The surgical approach to patients with abdominal aortic aneurysm and gastrointestinal malignancy remains controversial. We experienced two cases with abdominal aortic aneurysm and gastric cancer, which were treated by a one-stage operation using a different approach. At first, the operation for the aneurysm was done through a retroperitoneal approach and then, a partial gastrectomy for gastric cancer was done through a transperitoneal approach. The postoperative course of both cases was uneventful. The patients were discharge on the 19th and 21st postoperative days, respectively. This one-stage operation using different isolated approaches, such as the retroperitoneal approach for abdominal aortic aneurysm and transperitoneal approach for gastric cancer, was useful for the patients with abdominal aortic aneurysm and particularly early gastric cancer in terms of preventing an infection of the prosthetic graft. PMID- 1451822 TI - Co-variation between walking ability and circulatory alterations in patients with intermittent claudication. AB - Unselected patients (n = 183) with subjective symptoms of intermittent claudication were examined clinically and by various circulatory tests (calf blood-flow, ankle, toe pressures). The aims of the present study were to evaluate to what extent the central or peripheral circulation is limiting in unselected patients with subjective symptoms of intermittent claudication, to determine the co-variation between the maximum walking capacity and traditional haemodynamical measures mentioned above and to evaluate to what extent a traditional bicycle ergometer exercise test and treadmill walking test give similar information regarding maximum performance. Eighty-five per cent of all patients were or had been smokers and 16% were diabetics. The mean ankle/brachial blood pressure index was 0.58 +/- 0.02 and the average post-ischemic maximum calf bloodflow was 13.3 +/- 0.6 ml/min/100 ml tissue. Leg arterial insufficiency was the limiting factor of walking capacity in 90% of all patients at 87 +/- 2 W corresponding to a walking distance of 282 +/- 13 m, while leg exhaustion was the limiting factor in 80% of the patients during test on the bicycle ergometer at maximum 84 +/- 2W. The mean maximum walking capacity for all patients was 86 +/- 3W and the mean maximum capacity on the bicycle ergometer was 87 +/- 2W. The ankle/brachial index showed only a weak correlation (r = 0.30, p < 0.002) to walking capacity. Our results demonstrate that the maximum walking capacity on a treadmill agrees with mean values of maximum exercise capacity on a bicycle ergometer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451823 TI - Epidemiology of abdominal aortic aneurysm: the effect of differing definitions. AB - There have been several published definitions for abdominal aortic aneurysm (AAA), however, it is not known how different definitions affect what is reported. This paper presents an evaluation of three definitions taken from the literature on (a) aneurysm frequency, (b) prevalence rate and (c) prevalence ratio from an ongoing case-control study evaluating whether male siblings of patients with known AAA have a higher prevalence of aneurysms compared to a control group. Depending on the definition used, the frequency of AAA could vary from a low of five to a high of 23; the prevalence of AAA in siblings could range from 2.1 to 18.8. Changing definitions alters the prevalence ratio (risk of disease) in both magnitude and direction. On the one hand, male sibling of affected patients are at approximately one and a half times (1.6) greater risk of having an AAA compared to controls, whereas using a different definition they are at less than half the risk (0.3). PMID- 1451824 TI - Endarterectomy of the superficial femoral artery: a procedure worth reconsidering. AB - The preferred management of superficial femoral artery occlusive disease remains unresolved. The oldest technique for restoring vascular continuity, endarterectomy, has been largely replaced by bypass operations and percutaneous transluminal angioplasty. We have continued to perform semi-closed endarterectomy in selected cases and review here a series of 231 consecutive cases in 197 patients treated during the last 10 years. The indication for the endarterectomy was disabling claudication in 186 operations (80%), rest pain in 21 (9%) and gangrene in 24 (11%). The superficial femoral artery abnormality consisted of 1 10 cm occlusion in 52 cases (23%), > 10 cm occlusion in 96 (41%), single stenosis in 21 (9%), multiple stenoses in 28 (12%) and it was unknown in 34 cases (15%). Postoperative mortality was 0.8% with a complication rate of 10%. Five year cumulative primary patency was 71% overall, 75% in patients with disabling claudication, 61% in those with rest pain and 46% in those with gangrene. Eight year patency was 55% (S.E. 5.4%). No difference in 5-year cumulative patency was seen between treatment for stenosis or occlusion (74 and 70%, respectively). The results of earlier studies and the current study raise the question of whether endarterectomy should be the first treatment of choice in obstructive lesions of the superficial femoral artery. The results of endarterectomy are better than can be achieved with angioplasty and compare well with the results of femoropopliteal bypass. Endarterectomy has specific advantages above femoro-popliteal bypass: the autologous saphenous vein is spared for future use and in case of failure of the endarterectomy, femoro-popliteal bypass remains possible.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451825 TI - A method of single-incision, four compartment fasciotomy of the leg. AB - A method of achieving four compartment fasciotomy of the leg using a single skin incision is described. This procedure may be used to decompress the leg in acute compartment syndromes. PMID- 1451826 TI - Verrucous carcinoma (epithelioma cuniculatum) plantare. AB - A case of plantar verrucous carcinoma is described. The lesion was treated as an ischaemic ulcer before the true nature was recognised. Prior to the diagnosis the patient had a femoro-popliteal arterial bypass graft performed. An amputation was undertaken once the diagnosis was established. PMID- 1451827 TI - Ruptured mycotic aneurysm of the abdominal aorta in childhood. AB - Aortic aneurysms are exceedingly rare in childhood and, when mycotic, the risk of rupture is high. We report a case of ruptured mycotic abdominal aortic aneurysm presenting in a 9 year old girl, that was successfully repaired after initial misdiagnosis. PMID- 1451828 TI - Fibromuscular dysplasia of visceral arteries. AB - The case histories of two patients with combined renal and extra-renal fibromuscular dysplasia are presented. Readers are reminded of this rare but important condition as a cause of obscure abdominal symptoms and abdominal bleeding in the absence of atherosclerotic aortic aneurysm. The aetiology, histology, and management of the condition are discussed. PMID- 1451829 TI - Delayed presentation of bilateral popliteal artery injury. AB - We describe a patient who developed serious vascular complications following gunshot wounds to both popliteal fossae. There was minimal evidence of vascular injury on presentation to hospital, in particular ankle systolic pressures were normal. Five days following the initial injuries he was found to have a false aneurysm of the popliteal artery in his right leg and an arteriovenous fistula affecting the popliteal vessels of his left leg. The roles of arteriography and Doppler pressure studies in assessment of possible peripheral vascular injury following penetrating trauma are discussed. It is emphasised that a high index of suspicion and careful clinical review is essential if vascular injuries and their complications are not to be missed. PMID- 1451830 TI - First rib abnormalities in association with cervical ribs: a cause for postoperative failure in the thoracic outlet syndrome. PMID- 1451831 TI - Autumnal aneurysmal ruptures. PMID- 1451832 TI - Seasonal variation in the incidence of ruptured abdominal aortic aneurysm. PMID- 1451833 TI - Naftidrofluryl dose and vascular resistance. PMID- 1451834 TI - Chromosome preparation from human bone marrow--technique modified for immediate clinical investigation. AB - A modified method for chromosome preparation from bone marrow aspirates of normal individuals and leukaemic patients is described for immediate clinical investigation. Hanks' balanced salt solution at different concentrations was used for in vitro incubation and hypotonic treatment. The method yields quite a high mitotic index with good metaphase spreads. PMID- 1451835 TI - Quantification of neutral red pinocytosis by small numbers of adherent cells: comparative studies. AB - A colorimetric assay has been developed for studies on neutral red (NR) pinocytosis by small numbers (below 2 x 10(5)) of adherent cells cultured in 96 well plates. The NR uptake per cell mass was much higher in the sea urchin perivisceral adherent cells and human HL-60 cell line monolayers than in the murine and Atlantic salmon macrophages. The apparent difference points to the usefulness of this novel assay in comparative studies. PMID- 1451836 TI - Properties of acid beta-N-acetyl-D-glucosaminidase from cock semen. AB - Two forms (I and II) of beta-N-acetyl-D-glucosaminidase from cock seminal plasma and one form (III) from spermatozoa were separated by chromatofocusing. The active enzyme forms I and II had pI values of 6.6 and 6.3, respectively, while form III had two subforms with pI values of 6.3 and 6.1, as determined by polyacrylamide gel electrofocusing. The molecular weights were 76,000 for forms I and III and 32,000 for form II. The optimum pH of enzyme forms I and III ranged from 3.6 to 4.0. In contrast, form II showed one distinct maximum at pH 3.7. The Km values obtained with p-nitrophenyl-beta-N-acetyl-D-glucosaminide as substrate were 0.35, 0.28, and 0.39 mM for forms I, II, and III, respectively. It is assumed that both cock spermatozoa and cock seminal plasma contain a common, enzymatically active beta-N-acetyl-D-glucosaminidase subunit with M(r) about 32,000 and pI 6.3. PMID- 1451837 TI - Toxic effect of lead on fertility of inbred strain mice. AB - Males of inbred strains were orally given lead acetate water solution during 150 days. Changes were found in the structure of the seminiferous tubules and in spermatozoa. The pathological changes in Leydig cells brought about a decline in levels of androgens. PMID- 1451838 TI - Down-regulating effect on cellular immunity of the NSF17 factor produced by murine neonatal spleen cells fused with BW 5147 thymoma cells. AB - The non-specific factor NSF17 produced by mouse newborn splenocytes fused with BW 5147 thymoma cells was tested in vivo for its immunosuppressive activity. NSF17 administered i.p. in a single dose into adult mice significantly decreased the PHA-induced proliferative response of lymphocytes, regional graft-versus-host reaction, and delayed-type hypersensitivity. PMID- 1451839 TI - The influence of peat extract on the seminiferous epithelium of mouse testes. AB - Because of the interest in the peat extract as a potential therapeutic agent, its effect on the seminiferous epithelium cells was studied. Adult male mice were intraperitoneally injected with peat extract during 34 days. At intervals equal to the duration of the cycle of the seminiferous epithelium (every 8.5 days), gametogenic cells were quantitatively analysed. It was revealed that the peat extract causes a decrease in the production of the A1 spermatogonia, and as a result a decrease in the intensity of spermatogenesis. Besides, in some individuals disturbances of meiosis took place, leading to an increased degeneration of pachytene spermatocytes and formation of diploid spermatids. PMID- 1451841 TI - The state of the Medical Society of Delaware 1992. PMID- 1451840 TI - Effect of prolonged administration of insecticide (Cyhalothrin/Karate) on the blood and liver of rabbits. AB - A sublethal dose of Karate administered to rabbits produced a significant increase in the total erythrocyte count and packed cell volume after 15 days of administration, though no significant change was observed after 30 days. The transaminases (glutamate oxaloacetate transaminase, GOT; glutamate pyruvate transaminase, GPT) also increased after 15 days of treatment. The GPT activity increased 119% and 60% after 15 and 30 days, respectively. From amongst metabolites, glucose content increased 17% and 185%, while cholesterol decreased 40% and 66%, and bilirubin 84% and 61%, after 15 and 30 days, respectively. The hepatic AkP activity decreased 30%, while the GPT activity increased 44%. Other enzymes such as AcP, GOT and LDH remained unaffected. The concentration of other metabolites, except for FAA which increased 35%, remained unaffected. Histological changes were marked by atrophied hepatic cells and hypertrophied nuclei and nucleoli. A trend towards necrosis of hepatic cells was also observed. All these results indicate that Karate is moderately toxic to mammals. PMID- 1451842 TI - The prehospital use of nebulized albuterol on patients with wheezing whose chief complaint is shortness of breath. AB - The use of prehospital nebulized beta-agonists has become widespread, and their safety and efficacy has been documented. Our purpose was to study their broadened use and determine their effectiveness in specific sub-sets of wheezing patients. We conducted a six and one-half month prospective study to determine the benefit of nebulized albuterol treatments on a variety of wheezing patients whose chief complaint to paramedics was shortness of breath. Sixty-two patients were enrolled in the study and were subdivided into four groups based on patient history; asthma, COPD, asthma & COPD (A/C), and non-Asthma/non-COPD (NANC). The effectiveness of the treatment was evaluated objectively by peak expiratory flow rates (PEFR) obtained before and immediately after treatment and subjectively by the patients' evaluation of their own dyspnea. Changes in PEFR were subjected to analysis by a paired T-test. Albuterol was effective in increasing the PEFR in patients with asthma, COPD and NANC. Patients with both asthma and COPD did not demonstrate increased PEFR after treatment. The majority of all patients were subjectively improved after nebulized albuterol treatments. We conclude that aerosolized albuterol is safe and effective in the prehospital treatment of patients complaining of dyspnea who are wheezing. PMID- 1451843 TI - Is better access to medical care needed in Delaware? AB - Improved access will require more primary care providers, a reduction in administrative red tape, and a clientele with healthy lifestyles who know how to use the system appropriately. Prevention is a necessary component of access even though it often takes years to produce results and is usually not dramatic or glamorous (the heart attack which does not occur is hard to measure). Over time, the health of Delawareans should show improvement through appropriate access to medical care, which should not only be cost effective but add to the quality of life. PMID- 1451844 TI - Tax issues affecting physician recruitment and development. PMID- 1451845 TI - Advance directives. PMID- 1451846 TI - Physical therapy of any individual shall be administered only by a licensed physical therapist. PMID- 1451847 TI - Voluntary Initiative Program proposals, now implementation. PMID- 1451848 TI - Hepatic incidentalomas: imaging hemangiomas. PMID- 1451849 TI - Radiograph of the month. Pleural lipoma. PMID- 1451850 TI - 1991 end-of-year AIDS case summary. PMID- 1451851 TI - Defending the healthcare fraud case: parallel proceedings and collateral consequences. PMID- 1451852 TI - The noninstitutionalized elderly: ability to perform daily activities. PMID- 1451853 TI - Crime and punishment? PMID- 1451854 TI - Comment on hepatic incidentalomas. PMID- 1451855 TI - Schizophrenia or ambivalence. PMID- 1451856 TI - Current concepts in the diagnosis and management of aortic stenosis. PMID- 1451857 TI - Rheumatic fever: a case report. AB - The case of a previously healthy nine-year-old female who presented with a two week history of fever and five days of joint pain is discussed. She was admitted to the hospital, where the diagnosis of acute rheumatic fever was made. Although this diagnosis is made infrequently, it should be part of the differential diagnosis of persistent fever in patients presenting to the Emergency Department. PMID- 1451858 TI - Radiography of the month. Renal angiomyolipoma. PMID- 1451859 TI - Primary care physicians. PMID- 1451860 TI - The preexisting condition. PMID- 1451861 TI - Physicians as Johnnys-come-lately: overcoming misperceptions. PMID- 1451862 TI - [Functional occlusion puzzle. Directional points for form and function]. PMID- 1451863 TI - [Morita-Cyclarc system. Vacuum pouring with cover gas vents]. PMID- 1451864 TI - [Preparation of a prosthesis of cold polymerizing synthetic resin]. PMID- 1451866 TI - [Measurement procedures for improvement of accuracy of fit of cast dental objects]. PMID- 1451865 TI - [Light-curing tray resin for precision improvement of working models]. PMID- 1451867 TI - [Multi-color layer technique. Systems for individualization]. PMID- 1451868 TI - [Practice oriented use of modern composite blends and bonding technology]. PMID- 1451869 TI - [Metal-free restoration techniques. Pin-supported by In-Ceram]. PMID- 1451870 TI - [Ohara-titanium dental casting system. Centrifugal casting with argon cover atmosphere]. PMID- 1451871 TI - [Accurately fitting milled attachments in the double crown technique]. PMID- 1451872 TI - [Bending of Tenti modified Adams clasp. Principles of orthodontic technique]. PMID- 1451873 TI - [Contrasts between two full porcelain systems. 1. Optec-hsp vs. IPS-Empress]. PMID- 1451874 TI - [Four young parrots with massive prognathic problems]. PMID- 1451875 TI - [Arrangement of protuberance-free teeth in complete dentures]. PMID- 1451876 TI - [Individualized composite technique demonstrated in a case report]. PMID- 1451877 TI - [Bending the Adams clasp with the Nance-sling-forceps]. PMID- 1451878 TI - [Key to the success of teamwork in a dental laboratory]. PMID- 1451879 TI - [What happens when plastic must oppose porcelain? Argument for a weak complete denture against a fixed partial denture]. PMID- 1451880 TI - [Contrasts between two full porcelain systems. 2. Optec-hsp vs. IPS-Empress]. PMID- 1451881 TI - [Rematitan-pour-vacuum melting in two-chamber system]. PMID- 1451882 TI - [Preparation of tooth colored adhesive inlays. Prisma AP.H-inlay system]. PMID- 1451883 TI - [What the technician should be careful of in preparation of full porcelain artificial teeth]. PMID- 1451884 TI - [Prosthetic concerns in facial defects]. PMID- 1451885 TI - [Work guides for set-up and fitting of functional tooth relations]. PMID- 1451886 TI - Outcome and long-term effects of pregnancy in women with hyperprolactinaemia. AB - Twenty-four women with high circulating prolactin became pregnant on 39 occasions, of which 32 ended in delivery. Sixteen patients showed radiological evidence of pituitary tumour, 6 exhibited a normal CT and 2 had an empty sella. The pregnancies were induced in 4 patients after successful pituitary surgery, in 3 after surgery and medical treatment, and in the rest by bromocriptine (16) long acting repeatable bromocriptine (1) and methergoline (1). No major complications related to hyperprolactinaemia or its treatment were observed during pregnancy in the patients or offspring. Prolactin after pregnancy was lower than before (basal 95 micrograms/l, after 1st pregnancy 38 micrograms/l P < 0.002, after 2nd pregnancy 24 micrograms/l P < 0.005 compared to basal prolactin); this prolactin reduction tended to be greater in the 9 multiparous patients, but did not attain statistical significance, probably because the number of multiparous patients was too small. A new empty sella developed after delivery in 4 women and persisted in another 2, all of which were medically treated; prolactin fell in all 6 cases normalizing in 3; 4 of these patients had undergone two or more pregnancies. The mean period of follow-up from the last pregnancy was 41.6 months (8-101). These data suggest that pregnancy may hasten a tendency to spontaneous improvement of hyperprolactinaemia, and multiparity may be beneficial in this way. PMID- 1451887 TI - Paradoxical ovarian stimulations in the use of LHRH analogs. AB - In the case of in vitro fertilization, LHRH analogs are used to induce a hypophysial blockage before the phase of stimulation, via administration of exogenous gonadotropin. During in vitro fertilization attempts using LHRH analogs, the blockage is controlled after 14 days of treatment by measuring plasmatic estradiol and by pelvic ultrasonography. In this retrospective study, which concerned 1075 in vitro fertilization cycles, a paradoxical ovarian stimulation with LHRH analogs was observed in 93 cases (8.7%) with high estradiol levels and follicular growth (detected by ultrasonography), in spite of low FSH and LH levels. In 4 cases, a follicular puncture was performed, which made it possible to collect oocytes from which embryos were obtained, thus confirming the observed follicular growth and maturation. The most probable hypothesis explaining this phenomenon seems to be direct ovarian stimulation effectuated in vivo by LHRH analogs. This stimulation is only observed in certain patients, and, more frequently it seems, with certain LHRH analogs, which is probably due to a variation in the expression of ovarian LHRH receptors. PMID- 1451888 TI - A comparative analysis of two preparations of human chorionic gonadotrophin. AB - A biophysical analysis of two pharmaceutical preparations of human chorionic gonadotrophin (Endo and Profasi) demonstrated that both contained high hCG specific activity. HCG protein analysis by occlusion HPLC and SDS gel electrophoresis showed similar profiles for both products. Although the purified protein components of both preparations were similar their were differences in the contents of the unpurified preparations. The Endo preparation exhibited greater inter-vial variability and contained an unidentified aromatic substance which interacted with the desalting column. PMID- 1451889 TI - Cytogenetic analysis of 1508 spontaneous abortions originating from south Slovakia. AB - Knowledge with regard to the spontaneous abortion cytogenetics has been derived exclusively from populations of the highly developed countries; its full applicability to east-european populations living in the peculiar conditions of the former 'socialist countries' may be questioned. The consecutive series of 1912 spontaneous abortion products with identifiable embryonal tissue was collected in six maternal clinics in south Slovakia. 1508 specimens were set in culture. Among 926 (61.4%) successfully karyotyped abortions, 46.0% were chromosomally abnormal specimens. The proportion of the groups of abnormalities is similar to that in other large series, with the exception of a higher proportion of mosaics (14.3% of the abnormalities). The abnormality rate in the whole sample also lies within the range of values published. However, significant inter-regional variability has been established: the chromosome abnormality rate in the urban subsample is 47.8%, whereas the value was only 35.3% for rural southern districts. The anomaly rates are lower for all maternal ages and gestation phases in the country subsample. The possibility of the environmental diversity effect was discussed. No other major peculiarity of cytogenetic abortion characteristics can be determined in the population studied. PMID- 1451890 TI - The prognostic significance of maternal serum CA125 measurement in threatened abortion. AB - The prognostic predictive value of maternal serum CA125 measurement was investigated in 25 cases of threatened abortion. The women were non-smoker, had a ultrasonographically verified viable single fetus, and the gestational ages ranged from 7 to 12 weeks. Twenty-five healty pregnant women, with the same characteristics were used as the control group. The overall abortion rate was found to be 20% (5/25) in the study group. In serial measurements the mean serum CA125 level of the patients with an unfavorable pregnancy outcome was significantly higher than that of the patients with a favorable outcome. When the cut-off level of maternal serum CA125 was taken as > 65 U/ml in the first and > 60 U/ml in the second measurements of the study group, the risk of termination of the pregnancy by spontaneous abortion was 83.3% in the patients with elevated serum CA125 levels. No statistically significant difference was observed with respect to the duration of vaginal bleeding between the aborters and the patients with a favorable outcome. Nevertheless, when vaginal bleeding had been present for 3 days or more and there was high maternal serum CA125 activity, the abortion risk was found to be 100% (3/3). These findings suggest that the maternal serum CA125 measurement in threatened abortion can be useful to determine the extent of decidual destruction which is directly related to the outcome of pregnancy. PMID- 1451891 TI - Carbon dioxide laser treatment of cervical dysplasia in teenagers. AB - Over a 6-year period, 40 young women under 20 years of age with cervical intraepithelial neoplasia (CIN) grade I (58%) to grade III (10%) were treated by laser vaporisation or excisional conisation. This prevalence of CIN in young women (nearly 4% of laser-treated cases) underscores the need for detection of cervical abnormalities in all teenagers engaged in sexual relations. The colposcopically-guided carbon dioxide laser technique is the treatment of choice for vaporisation and conisation of intraepithelial lesions (extending to the periphery of the cervix in 20% of cases) and for vaporisation of associated condylomatous lesions of the cervix (75%), vagina (23%), vulva (48%) and/or anus (8%). PMID- 1451892 TI - An unusual type of endometrial cancer, related to tamoxifen? AB - Tamoxifen, which is increasingly being used in breast cancer patients, has been associated with an elevated frequency of endometrial carcinoma. To our knowledge not a single case of uterine serous papillary carcinoma (USPC) has been documented during tamoxifen treatment. No conclusions as to a causal relationship are yet being made, but if it is due to tamoxifen, we should advise a strategy for prevention, because this subtype is not as curable as endometrioid carcinoma. PMID- 1451893 TI - Ruptured intracranial aneurysm in pregnancy: a case report and review of the literature. PMID- 1451894 TI - Unsuccessful methotrexate treatment of a tubal pregnancy with a live embryo. AB - Two cases with unsuccessful local and systemic methotrexate (MTX) therapy of tubal pregnancy with fetal heart rate activity are reported. The three modes of therapy, the first with local potassium chloride solution injection, the second with local MTX injection, and the third with systemic MTX injection, failed in the resolution of viable ectopic pregnancy. Therapy of MTX in cases of tubal pregnancy with demonstrable fetal heart rate beats, should be reconsidered. PMID- 1451895 TI - Congenital absence of fallopian tube and ovary. AB - Absence of one or both uterine tubes and ovaries is a finding that has rarely been described. Two such cases are presented. In one the anatomical abnormalities were discovered during investigations for primary infertility, in the other the absence was discovered at the time of laparoscopic sterilisation. There are two possible aetiologies. The first involves an asymptomatic torsion of one or both adnexes during adult life or childhood, or even before birth. Alternatively, the absence may be congenital, due either to a defect in the development of the entire Mullerian and Mesonephric systems on one side, or to a defect localised to the region of the genital ridge and the caudal part of the Mullerian duct. PMID- 1451896 TI - Primary amenorrhea-galactorrhea with hyperprolactinemia and huge pituitary enlargement in juvenile primary hypothyroidism. AB - We report a girl with juvenile primary hypothyroidism revealed by growth retardation and a syndrome of primary amenorrhea-galactorrhea with hyperprolactinemia and suprasellar pituitary enlargement. Resolution of the pituitary enlargement and the amenorrhea-galactorrhea syndrome occurred after thyroid hormone replacement. No similar observation has been reported earlier in juvenile hypothyroidism. PMID- 1451897 TI - Antenatal uterine activity monitoring of women at increased risk of preterm labour. AB - The aim of the study was to investigate the usefulness of antenatal uterine activity monitoring in the management of women at increased risk of preterm labour on the basis of a past history of preterm birth or mid-trimester abortion. Uterine activity was recorded every 2 weeks between 20 and 28 weeks gestation. Activity was considered to be increased if pressure changes > 15 mmHg were detected. Fifty-eight women had uterine activity monitoring. Of them, 39 had normal uterine activity. Nineteen women had increased activity and they were randomized to either a study group (9) where the findings were revealed to the clinicians caring for them or a control group (10) where the findings were not revealed. There was no standard regimen of management for the study group except that additional uterine activity monitoring was performed to provide feed back to the clinicians about their interventions. The sensitivity, specificity, positive predictive value and negative predictive value of uterine activity monitoring for preterm births and for preterm births before 32 weeks were disappointing. Uterine activity monitoring was not useful for predicting births prior to 32 weeks; most of these were preceded by prelabour rupture of the membranes. The pregnancy outcome of women with increased uterine activity was not better if clinicians were aware of that increased activity than if they were not. PMID- 1451898 TI - Survival and long-term morbidity in preterm infants with and without a clinical diagnosis of periventricular, intraventricular hemorrhage. AB - The prognosis of clinically diagnosed periventricular, intraventricular hemorrhage on the survival and long-term outcome of 169 infants delivered at 24 to 30 weeks gestation who survived more than 48 hours was evaluated. Periventricular, intraventricular hemorrhage was confirmed by ultrasound in 37.9% of the survivors. In this group the survival rate was 64% and the major handicap rate was 14.6%. In contrast, the survival of infants who did not have a clinical diagnosis of periventricular, intraventricular hemorrhage was greater than 90% with a major handicap rate of only 3.2% (P < 0.0001 and P < 0.03, respectively). Infants with clinical diagnosis of periventricular, intraventricular hemorrhage who were found to have grades 1-2 by ultrasound had the same survival rate as those without a clinical diagnosis of periventricular, intraventricular hemorrhage (90.5%), while infants with grades 3-4 had a survival rate of only 51.2% (P < 0.01). We conclude, that preterm infants who survive longer than 48 hours and do not have a clinical suspicion of periventricular, intraventricular hemorrhage, have an excellent prognosis. In these circumstances brain sonography can be deferred without jeopardizing the infants' health. PMID- 1451899 TI - Understanding the pathophysiology of intra-uterine growth retardation: the role of the 'lower limb reflex' in redistribution of blood flow. AB - Doppler ultrasound was used to investigate the circulatory redistribution and underlying reflex responses of fetal cardiovascular compensation in 30 small-for gestational age (SGA) fetuses. The utero-placental bed, umbilical artery and vein, thoracic and abdominal aorta, internal and external cerebral arteries were evaluated. The values were compared to reference ranges constructed from 135 normal pregnancies, correlated to fetal blood gases obtained by cordocentesis and compared to the outcomes. In Group I (mortality and morbidity), all fetuses had loss of end-diastolic frequencies (L-EDF) in the abdominal aorta (100%), but only 20 (87%) and 13 (56%) had L-EDF in the thoracic aorta and umbilical artery respectively. High vascular resistance in the placental bed and low impedance in the middle cerebral and common carotid arteries was found in 14 (61%), 12 (52%) and 20 (87%) fetuses, respectively. In Group II (Healthy infants) two fetuses had high utero-placental vascular resistance and one had brain-sparing. Doppler indices did not always reflect fetal hypoxaemia demonstrating that redistribution in SGA fetuses may not be triggered by a fall in pO2, and that hypoxaemia is an associated pathology but may not be the underlying cause. It is postulated that redistribution in SGA fetuses is regulated by reflex mechanisms (the 'lower limb reflex') which result in severe vasoconstriction in the abdominal aorta, mesentery and carcass, favouring the brain and cardiac muscles. This mechanism explains the good predictive value of L-EDF in the abdominal aorta for poor neonatal outcome (sensitivity, specificity and positive predictive value, all 100%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451900 TI - A comparative study of intramuscular ketorolac and pethidine in labour pain. AB - A single dose block randomised double-blind study comparing intramuscular ketorolac, 50 mg of pethidine and 100 mg pethidine was carried out in multiparous women. Pain intensity and sedation effect were recorded at inclusion to the study, half hourly for the first 2 h, then hourly until 6 h after delivery. Maternal and neonatal side effects were noted including the Apgar scores and the baby's requirements for resuscitation. All three treatments are relatively ineffective in relieving labour pain. There was no difference in the analgesic efficacy between the two doses of pethidine but both doses of pethidine were statistically more effective compared with ketorolac. There was no difference in the retrospective assessment of the three groups or when comparison was made with the previous labour. A similar number of patients required further analgesia in each group. In all three groups, no adverse effect occurred in the mother or fetus. Maternal sedation and fetal depression were statistically less in the ketorolac group. Although ketorolac had inferior analgesic effect, its use was not associated with clinically significant sequelae and it showed a superior safety profile compared with either dose of pethidine. The study was not powerful enough to detect a difference between 50 mg and 100 mg of pethidine. PMID- 1451901 TI - Reduced albumin binding of MADDS--a measure of bilirubin binding--during pregnancy and delivery. AB - It was the purpose of the present study to investigate whether the decrease in the ability of plasma albumin to bind bilirubin, noted in pregnancy and during delivery, takes place in one step, during pregnancy alone, or in two steps, during both pregnancy and delivery. Furthermore, it was investigated whether a possible decrease during labor was related to the method of delivery itself. The material comprised (a) 17 pregnant women who delivered vaginally; (b) 25 women who were delivered by Cesarean Section; and (c) a group of 25 non-pregnant women. The reserve albumin concentration for binding of MADDS (a measure of the binding of unconjugated bilirubin), the total albumin concentration and the ratio between them were constant in the 6-week period up to birth and were significantly lower than the corresponding values in the non-pregnant group. During labor a significant decrease in reserve albumin and ratio of reserve albumin to total albumin was observed, while no change in the total albumin concentration was noted. No significant difference in reserve albumin concentration, total albumin concentration and ratio between them was found when the group of mothers who delivered vaginally was compared to the Cesarean Section group. It is concluded that the decrease in the ability of plasma albumin to bind unconjugated bilirubin takes place stepwise. The first step is a significant reduction during pregnancy followed by a further decrease during labor. The method of delivery is of no significance. PMID- 1451902 TI - Shape of the myosin head. PMID- 1451903 TI - Some aspects of activation and inhibition of rat brain lipoxygenase. AB - 1. Regulatory properties of lipoxygenase activity in rat brain cytosol were studied using linoleic acid (LA) as a substrate. 2. A change in the absorbance at 234 nm was biphasic when a mixture of LA and pre-formed hydroperoxide (LA-OOH) was incubated with freshly isolated native brain cytosol. Initially, a rapid depletion of LA-OOH was observed with a concomitant formation of LA-oxo compounds. This phase was followed by LA dioxygenation. 3. Both hydroperoxidase and dioxygenase activities of lipoxygenase were inhibited by micromolar concentrations of classic lipoxygenase inhibitors (phenidone, 5,8,11 eicosatriynoic acid and nordihydroguaiaretic acid). 4. The dioxygenase activity in dialysed cytsool was stimulated by nanomolar concentrations of H2O2 and micromolar concentrations of LA-OOH and it was inhibited by serotonin, dopamine and norepinephrine (IC50 25-43 microM). PMID- 1451904 TI - Allosteric regulation of rat testis mitochondrial aldehyde dehydrogenase by capronaldehyde and magnesium ion. AB - 1. The influence of Mg2+ on the kinetic behaviour of mitochondrial aldehyde dehydrogenase from rat testis has been investigated using capronaldehyde as substrate. 2. The kinetic data, obtained by numerical analysis of the progress curves of aldehyde oxidation, were fitted to a modified version of the Monod Wyman-Changeux model and the fitting procedure resulted in a good correspondence between theoretical and experimental reaction rates over a wide range of capronaldehyde and Mg2+ concentrations. 3. According to the model, the tetrameric enzyme is in equilibrium between two conformational states R and T which display comparable affinities for capronaldehyde (the dissociation constants are 0.17 and 0.3 microM, respectively), but different catalytic power (VT = 2VR). The T state can bind with lower affinity a second molecule of aldehyde (K = 2.5 microM). 4. Mg2+ stabilizes the T state (the dissociation constants for the R and T states are 2.2 and 0.12 mM, respectively) and acts as a strong activator of the R state, but as a weak inhibitor of the T state. In the absence of substrates and Mg2+, the R<-->T equilibrium favors the R state ([T]/[R] = 0.16). 5. The model is able to predict the kinetic behaviour also when the NAD+ concentrations are not saturating and when inhibitory effects by NADH are taken into account. PMID- 1451905 TI - Rat erythrocyte glycophorins can be isolated by the lithium diiodosalicylate method used for other glycophorins. AB - 1. The lithium diiodosalicylate/phenol method, widely employed for the isolation of membrane sialoglycoproteins (glycophorins) from mammalian erythrocytes, was applied for the first time to the purification of homologous glycoproteins from rat erythrocyte membranes. 2. The resulting preparations showed to be composed of four components, fractionated on SDS-PAGE. All four were positive for periodic acid-Schiff's reagent stain, the two largest of them being major. 3. Isolated rat glycophorins accounted for 60% of the ghost sialic acid and 1.5% of their protein. The presence of O-acetyl groups was confirmed in one-third of the sialic acid residues. 4. The molecular masses of the four glycophorin components were determined by a method which takes into account the anomalous mobility of glycoproteins on SDS-electrophoresis. Estimated values thus obtained for the actual molecular masses were 74, 32, 25 and 17 kDa. PMID- 1451906 TI - The condensing action of Mg2+, hexamminecobalt3+ and spermidine3+ on chromatin with gene regions activated by 17-beta estradiol. AB - 1. Hepatic vitellogenin synthesis was induced by injecting 17-beta estradiol into fish. Liver nuclei were incubated with the endonuclease EcoRI at an increasing concentration of Mg2+ (0.15-1.50 mM), hexamminecobalt3+ or spermidine3+ (0.10 1.00 mM). Chromatin was separated into a 5000 g supernatant, S-fraction, and pellet fraction. 2. The release of chromatin into the S-fraction was higher for the induced than the control chromatin. Hybridization of the vitellogenin gene retained in the pellet fraction of the controls was unaffected by the individual cations. After activation of the vitellogenin gene, Mg2+ at its lowest concentration retained a high amount of the vitellogenin gene in the pellet fraction. The level of hybridization decreased by increasing the Mg2+ concentration. Retention of the gene rose by adding hexamminecobalt3+ and more so by adding spermidine3+. 3. The condensing action of spermidine3+ was extended to the activated vitellogenin gene regions of chromatin. PMID- 1451907 TI - Gluconeogenesis from methylglyoxal in isolated murine hepatocytes. Does an alternative pathway exist in which pyruvate is not an intermediate? AB - 1. Gluconeogenesis from alanine can be prevented by the addition of monoiodo acetic acid (an inhibitor of glyceraldehyde 3-phosphate dehydrogenase), while glucose production from methylglyoxal is only partially inhibited by this compound. 2. It is supposed that methylglyoxal can enter gluconeogenic sequence not only at pyruvate. PMID- 1451908 TI - Metabolic utilization of muscular L-proline in 24-hr starved rats. AB - 1. The aim of this paper was to study the in vivo skeletal muscle L-proline related to its destination to other key tissues such as liver and intestine as well as to give some insight into the role of blood cells in proline handling. 2. L-U-[14C]Proline was injected intramuscularly and following by sampling of blood, liver, intestine and contralateral muscle at 20 and 30 min after injection. 3. The distribution of radioactivity between blood cells and plasma and in total and individual amino acids, protein and glycogen fractions was determined in the above tissues. 4. The pattern of well fed rats was compared with those submitted to 24-hr complete starvation. 5. During starvation a minor degree of proline oxidation occurs. 6. The main destruction of proline in the liver seem to be the synthesis of proteins. 7. The radioactivity recovered in the blood proline fraction of starved rats is twice that of the fed rats and that it could be attributed mainly to plasma protein. 8. We have obtained in vivo evidence for the role of erythrocyte in the interorgan proline transport. PMID- 1451909 TI - Purification and characterization of glutathione S-transferase isozymes in dog lens. AB - 1. Two isozymes of glutathione S-transferase (GST-dl1 and GST-dl2) were purified to homogeneity from dog lens. 2. The subunit size and the isoelectric point were determined to be 24,000 and > pI 9.5 for GST-dl1 and 22,000 and pI 8.1 for GST dl2. 3. It was judged that GST-dl1 is a class alpha enzyme and GST-dl2 belongs to class pi on the basis of their immunological properties and N-terminal amino acid sequences. 4. The expression pattern of glutathione S-transferase isoenzymes in dog lens is different from that in pig, rat and bovine lenses. PMID- 1451910 TI - Steady-state kinetic properties of FoF1-ATPase: the pH effect. AB - 1. The kinetic properties of FoF1-ATPase from submitochondrial particles isolated from rat heart were studied, with emphasis to the pH effect. The velocity data were treated according to the Hill equation, and the results were discussed on the basis of the knowledge on the soluble F1-ATPase properties. 2. Three kinetic phases were observed in the range of pH 6.0-8.5, with apparent dissociation constant values (K0.5) of 0.001, 0.04 and 1.5 mM (respectively sites I, II and III) at pH 7.0. Their contribution to the total activity of the enzyme were pH dependent on the range of 6.0-7.0, but not from 7.0 to 8.5, where the maximal velocity (V) for site III was some 4-fold larger than for site II, and the total V of sites II and III was some 40-fold larger than V assumed for site I. Therefore, two catalytic sites seem to participate significantly in the catalysis at steady-state condition. 3. Azide increased the sites II and III K0.5 values as well as decreased the site III V. In the presence of bicarbonate these two sites were not distinguishable, and the kinetic parameters at pH 7.0 were similar to those for sites II and III combined. Both azide and bicarbonate did not have a significant effect on site I, and this behavior was not pH-dependent. 4. The studies on the effect of pH on the kinetic parameters showed the following results: (1) the optimum pH for V was around 8.5; (2) decrease in the K0.5 values at pH below 7.0 for site II, and increase at pH over 7.0 for sites II and III; (3) in the pH range of 6.0-8.5 the Hill coefficient increased for site II, decreased for site III, and an intermediary effect was observed for the sites II and III combined, with a Michaelis-Menten behavior in the highest affinity pH, which was found in the physiological range. PMID- 1451911 TI - Characterization of rat liver nuclear proteins which recognize the cAMP responsive element. AB - 1. The data herein reveal the existence of cAMP-responsive element (CRE)-binding factors (CRF) in the nuclear extracts from cAMP-treated rat liver. 2. DNAase I and DMS footprinting analysis showed that the CRFs protected the CRE (-77 to -92) in the phosphoenolpyruvate carboxykinase (PEPCK) promoter and the TGACGTCA motif in a consensus oligodeoxynucleotide based on the sequence of the CRE's of 6 cAMP regulated genes (C32mer). 3. Competition assays indicate that the CRF(s) is a CGTCA-specific, ATF/CREB-like factor(s). 4. Southwestern (SW) blot analysis detected 2 apparent CRFs which have molecular weights of about 30 and 32 kDa, respectively. 5. Based on the comparison of the size and binding specificity of the CRFs with the CREBs reported to date, the CRFs appear to be novel CRE-binding nuclear factors. PMID- 1451912 TI - Differential effects of aluminum ion on smooth muscle calpain I and calpain II activities. AB - 1. In millimolar Ca2+, smooth muscle calpains I and II were inhibited by aluminum ion. 2. At sub-millimolar Ca2+, calpain II, but not calpain I, was activated by low millimolar aluminum ion. 3. Calpastatin inhibited aluminum ion-activated calpain II. 4. Aluminum ion-activated and Ca(2+)-activated calpain II gave almost identical patterns of desmin cleavage. 5. Aluminum-activated calpain II, unlike the Ca(2+)-activated enzyme, did not autolyze and retained its proteolytic activity over extended periods of time. PMID- 1451913 TI - Fluorescamine-induced membrane permeability in mitochondria. AB - 1. Addition of fluorescamine (75 microM) to mitochondria induced an increase in membrane permeability. 2. The leakiness of the inner mitochondrial membrane is characterized by extensive release of accumulated Ca2+, collapse of the transmembrane potential, mitochondrial swelling and efflux of matrix proteins, among them, malate dehydrogenase. 3. These effects were diminished by supplementing the media with 1 mM phosphate, and partially prevented by Mg2+. 4. These results indicate that the primary amino groups of membrane components contribute, partially, to the maintenance of the permeability barrier in mitochondria. PMID- 1451914 TI - Protein kinase NII from calf thymus chromatin. Isolation, characterization and some functional properties. AB - 1. A protein kinase type II was purified from calf thymus chromatin using ammonium sulphate fractionation, ion exchange chromatography on DEAE and phosphocellulose and affinity chromatography on phosvitin- and casein-sepharose columns. 2. The enzyme moves as a single band in non-denaturing gel electrophoresis at pH 8.3, which coincides with the enzyme activity assayed on gel slices. 3. Sodium dodecyl sulphate gel electrophoresis shows three separate polypeptide chains having M(r) of 40,000, 38,000 and 25,000, respectively. The native M(r) was about 130,000, as measured by HPLC on Superose 12 column, suggesting a subunit structure of alpha, alpha', beta 2 type. The enzyme incubated with [gamma 32P]ATP or [gamma 32P]GTP as phosphoryl donors undergoes autophosphorylation in the M(r) = 25,000 subunit. 4. The enzyme phosphorylates casein (Km = 7 microM) and phosvitin (Km = 5 microM) but not histones and was strongly deactivated by Zn2+ ions (I50 = 0.05 mM) and heparin (I50 = 0.1 micrograms/ml). 5. The enzyme seems to be the major phosphorylating system present in the 0.35 M NaCl chromatin extract of calf thymus. The RNA polymerase II from calf thymus and RNA polymerase from E. coli are both phosphorylated by protein kinase NII. The effect of phosphorylation, which causes a remarkable increase of DNA transcription rate, was studied in vitro and extensively discussed. PMID- 1451915 TI - Lysosomal beta-hexosaminidase is highly resistant towards proteolytic degradation in vitro. AB - 1. A partially purified enzyme preparation of beta-hexosaminidase from human fibroblasts was treated with proteases and the effect on its molecular weight and enzymatic activity was studied. 2. Both the forms A and B of the enzyme appeared to be resistant to a protease treatment that degraded the majority of the contaminating proteins to a large extent. 3. The same result was obtained with enzyme preparations from cells treated with tunicamycin. 4. Also the molecular weights of the individual polypeptide chains of the enzyme were not decreased, as was shown by SDS-PAGE, followed by immuno-blotting. PMID- 1451916 TI - pH dependent kinetic studies of lipoamide dehydrogenase catalysis. AB - 1. Kinetic studies of lipoamide dehydrogenase and its modified enzymes catalyzing lipoamide oxidoreduction and ancillary reactions at various pH are compared. 2. The asymptotic kinetics of lipoamide oxidoreductions switch between the ping pong and ordered mechanisms by varying pH of the reactions. 3. pH-rate profiles of these reactions are bell-shaped suggesting the participation of 2 ionizable residues with pK values of 6.6 +/- 0.5 and above 8 respectively. 4. The unusually high pK value for the catalytic site histidine is attributed to its involvement in an ion-pair formation. 5. In the absence of the catalytic site histidine, the pH-rate profile for the lipoamide reduction of the photooxidized enzyme is no longer bell-shaped but it is similar to those of the transhydrogenation and NADH oxidation of the native enzyme. 6. This implies the participation of a low-pK protonated group in these reactions. PMID- 1451917 TI - Cytotoxicity and cytokinetic effects of mitomycin C and/or photochemotherapy in a human colon adenocarcinoma cell line. AB - 1. The cytotoxicity and cytokinetic effects of Mitomycin C (MC) and/or photochemotherapy (PCT) in cultured human colon adenocarcinoma (WiDr) cells were investigated using colony formation to determine cell survival and DNA flow cytometry to analyze cell kinetics. 2. A low concentration of MC (0.01 micrograms/ml) caused accumulation of cells in late S and early G2 phase; higher concentrations (0.05-0.5 micrograms/ml) induced accumulation of the cells in mid and early S phase. 3. The effects of the lowest concentration of MC (0.01 micrograms/ml) were reversible upon removal of the drug, whereas a higher concentration of MC (0.1 micrograms/ml) resulted in a permanent inhibition of cell cycle progression. 4. The sensitivity of Photofrin II-loaded cells to PCT can be enhanced significantly by the addition of MC. 5. The MC-induced accumulation of the cells in S phase may be one reason for the increased cytotoxicity of PCT combined with MC. 6. The data suggest that MC may also inhibit repair of PCT-induced DNA damage. PMID- 1451918 TI - Conversion of skeletal tartrate-sensitive acid phosphatases into tartrate resistant isoenzymes in vitro. AB - 1. Chicken skeletal tartrate-sensitive (TsACP) and -resistant (TrACP) acid phosphatase isoenzymes could be separated from each other by carboxylmethyl sepharose ion exchange chromatography. 2. Chicken skeletal TsACP showed a gradual time-dependent loss of sensitivity to tartrate inhibition when incubated at room temperature, but not at 4 degrees C. 3. The loss of sensitivity to tartrate inhibition was associated with an activation of the enzyme activity. 4. These changes were accompanied with a shift in the electrophoretic mobility of the enzyme activity from a large molecular sized form to a smaller molecular sized form that resembled the freshly prepared TrACP on the native acidic polyacrylamide electrophoresis gels, and on molecular sieve Superose-12 Fast Protein Liquid Chromatography. 5. Kinetic evaluations of the biochemical properties of the "converted" TsACP activity resembled the TrACP. 6. The apparent "conversion" was not unique to chicken TsACP, since similar "conversion" was observed with partially purified preparations of bovine bone matrix TsACP and of human osteoblastic TsACP. 7. Addition of several serine protease inhibitors did not prevent the "conversion". 8. These findings are consistent with the possibility that skeletal TsACPs are precursors of skeletal TrACPs. PMID- 1451919 TI - The effects of exercise and feeding on the activity of lipoprotein lipase in nine different adipose depots of guinea pigs. AB - 1. The activity of lipoprotein lipase (LPL) was measured in whole adipose tissue from 9 identified adipose depots of sedentary, fasting adult guinea pigs and following 30 min of exercise or voluntary ingestion of chow, and in adipocyte and stromal-vascular fractions from exercised specimens. 2. In sedentary, fasting specimens, LPL activity was up to 4 times higher in the small intermuscular depots than in the perirenal and epididymal depot (Table 1). 3. LPL activity increased significantly after feeding only in the large superficial depot, groin, and in the perirenal depot. LPL activity decreased after exercise only in the 2 intermuscular depots and in small anterior superficial depots. These effects of exercise were consistently greater in males than in females (Table 3). 4. Following exercise, there was up to twice as much LPL in the adipocytes as in the stromal-vascular fraction of the intermuscular depots, about 50% more in adipocytes from the minor superficial depots and about equal quantities in the 2 fractions of the intra-abdominal and groin depots (Table 2). 5. The data demonstrate the physiological inhomogeneity of both superficial and internal adipose depots, and are consistent with the hypothesis that LPL originating from adipose tissue may enter the circulation. PMID- 1451920 TI - Vegetable foods in weaning. AB - Vegetable foods (cereals, non-starchy vegetables, legumes) make a unique nutritional and metabolic contribution during weaning. They provide proteins that are of low biological value individually but whose value can be raised by consuming appropriate combinations: minimal amounts of lipids, mostly essential polyunsaturated fats; complex carbohydrates; and soluble fibre, which are fermented by colonic flora to short-chain fatty acids that have beneficial effects. Insoluble fibre, minerals, trace elements and vitamins are also nutritionally important components of vegetable foods. Vegetable foods lower the calorific density of meals, modulate nutrient and antigen absorption, and promote a physiological copropoiesis. Recent nutritional surveys have shown that 12-month old children eat an excessive amount of animal proteins. Whole cereals and non starchy vegetables, including whole legumes, should be routinely eaten during weaning to improve nutritional balance and to make children accustom to eating fibre, which has prophylactic properties. The daily intake of fibre should be progressively increased to 5 g during the first year of life. PMID- 1451921 TI - The effect of Vivida cream as compared with placebo cream in the treatment of sun damaged or age-damaged facial skin. AB - Vivida when used orally has been previously shown to be effective in treating degenerated skin of women. In the present study, 30 women with moderate to severe sun-damaged facial skin applied Vivida cream twice daily for 120 days on one side of the face and placebo to the other. Vivida was significantly (P < 0.001) more effective than placebo in improving wrinkles. The effects of Vivida cream on mottles and telangiectasis were also significantly (P < 0.01) greater than those of placebo. Scanner measurement showed that epidermal thickness increased from 0.13 mm to 0.29 mm and dermal thickness from 0.91 mm to 1.29 mm on the Vivida treated side; only minimal changes were observed on the placebo-treated side. The elasticity index increased from about 50% to 69% on the Vivida-treated side and from 49% to 50% on the placebo-treated side. PMID- 1451922 TI - Pregnancy by means of tubal insemination and subsequent spontaneous pregnancy in rabbits. AB - The purpose of the study was to determine whether or not physical stimulation by tubal insemination had any unfavourable influences upon the tubal fimbria. Tubal insemination was carried out on 14 rabbits and subsequent pregnancy results were monitored. After a period of 69-123 days following tubal insemination, 10 of the rabbits were mated spontaneously and these rabbits were then monitored for pregnancy. Newborn were obtained, with normal gestation periods in six out of the 14 rabbits, following tubal insemination and all 10 of the rabbits that were mated spontaneously with males following tubal insemination subsequently delivered. It is concluded that physical stimulation by tubal insemination does not produce adhesive changes on the tubal fimbria. PMID- 1451923 TI - Onset and duration of the effects of three antihistamines in current use- astemizole, loratadine and terfenadine forte--studied during prolonged, controlled allergen challenges in volunteers. AB - In a three-way, double-blind, crossover study the onset of action and effects at the end of the dosing interval of 10 mg/day astemizole, 10 mg/day loratadine and 120 mg/day terfenadine forte given for 3 days to six atopic volunteers were assessed using the Vienna challenge chamber (VCC). With each treatment, two long term pollen challenges were performed in the VCC: the first to assess the onset of action started 1 h before the first dose and lasted continuously for 5 h; the second to assess the effects at the end of dosing took place 21 h after the last of the three doses and lasted 3 h. All three drug treatments initiated 1 h after the beginning of challenge with grass pollen reversed the adverse effects of challenge on the subjective symptoms (runny, blocked or itchy nose, sneezing, itchy eyes, tears) and the objective parameters (nasal secretions, nasal resistance, nasal flow, flow increase, nasal peak flow) within 1-3 h. The mean time to onset of action was 107 min for astemizole, 117 min after treatment for loratadine and 153 min for terfenadine forte. During the second allergen challenge, 21-24 h after intake, astemizole consistently provided better protection for all parameters than did loratadine or terfenadine forte; however the differences were not statistically significant. PMID- 1451924 TI - Clinical appraisal of vinpocetine for the removal of intractable tumoral calcinosis in haemodialysis patients with renal failure. AB - Previous studies have shown that vinpocetine [14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine] scavenges minerals and/or metals in the soft tissues of rabbits with artificially induced arteriosclerosis. The present study was carried out to determine whether or not vinpocetine would bring about the removal of intractable tumoral calcinosis in haemodialysis patients with renal failure. After administration of 15 mg/day vinpocetine for 3-12 months in haemodialysis patients with X-ray evidence of tumoral calcinosis, calcinosis was completely eliminated in all eight cases. Serum alkaline phosphatase and bone osteocalcin concentrations tended to decrease after treatment with vinpocetine compared with before treatment. Vinpocetine thus appears to be an effective scavenger of tumoral calcinosis in haemodialysis patients with renal failure without any side-effects during treatment. PMID- 1451925 TI - Low-dose sultamicillin oral suspension in the treatment of mild to moderate paediatric infections in Turkey. AB - A total of 101 children (47 males, 54 females; age range, 3 months-16 years) with mild to moderate upper or lower respiratory tract infections, or skin and soft tissue infections entered a clinical study conducted at two centres in Izmir, Turkey. The children received a mean daily dose of 25 mg/kg sultamicillin oral suspension administered as two equal doses approximately 12 h apart. In total, 100 children met all requirements for evaluability and were included in the clinical efficacy assessment, and 49 children were evaluated for bacteriological efficacy. Clinical cure was reported by the investigators in 93 patients, improvement in six and failure in only one. The bacteriological eradication rate of isolated pathogens was 100%. Of the 101 patients evaluated for drug safety, four experienced adverse drug-related or possibly drug-related reactions. All side-effects were gastro-intestinal and diarrhoea was reported in three patients. No discontinuation of therapy was reported, nor were any significant laboratory abnormalities recorded. PMID- 1451926 TI - An open non-comparative pilot study of the safety and efficacy of oral sultamicillin in the treatment of mild to moderate upper respiratory tract infections in children. AB - A total of 49 children (20 females, 29 males; age range, 6 months-12 years) with upper respiratory tract infections (otitis media, sinusitis, pharyngitis and/or tonsillitis) were treated orally with 25 mg/kg.day sultamicillin suspension in two equal doses for an average of 9.2 days. There was bacteriological evidence of sultamicillin-sensitive pathogens in 44 patients prior to treatment. On completion of treatment, 42 (85.7%) patients were rated as clinically cured and there was improvement in the remaining seven (14.2%) patients. Pathogens were totally eradicated in 32/44 (73.7%) cases but were still present in two (4.5%) and in 10 cases follow-up bacteriological evaluation was not possible. Tolerability of sultamicillin was good and only three possible or probable treatment-related adverse events were recorded. PMID- 1451927 TI - An open comparative study of the efficacy and safety of sultamicillin versus cefaclor in the treatment of acute otitis media in children. AB - In an open study, children (age range 6 months-12 years) with otitis media due to a bacterial infection were treated orally with 50 mg/kg sultamicillin (n = 30) in two equal doses each day for a mean of 10 days, or 40 mg/kg cefaclor (n = 30) in three equal doses each day for a mean of 11 days. Earache was rapidly improved by either treatment; none of the 27 evaluable sultamicillin-treated or the 29 evaluable cefaclor-treated patients had earache after 8-10 days. Other signs and symptoms (reddened eardrums, perforated eardrums, middle ear fluid, hearing loss) gradually improved during treatment. All the pathogens isolated from patients in the sultamicillin treatment group were eradicated, as were all but one of the pathogens isolated from patients in the cefaclor treatment group. In the sultamicillin treatment group 65.4% of patients were cured and 34.6% were improved, and in the cefaclor group 65.5% were cured and 31.0% improved, but there was one treatment failure. Study drug-related adverse events were experienced by 33.3% of sultamicillin- and 40.0% of cefaclor-treated patients, all but one (urticaria in a cefaclor-treated patient) were gastro-intestinal. The dose administered was reduced by approximately 50% in patients experiencing adverse effects. This did not lead to any reduction in efficacy and no patient was withdrawn due to adverse events. PMID- 1451929 TI - Treatment of lower respiratory tract infections with sultamicillin. AB - Oral tablets containing 375 mg sultamicillin were used to treat 30 adult patients of either sex suffering from lower respiratory tract infections. The dose used was one tablet every 12 h for 22 cases and one tablet every 8 h for eight cases. The duration of therapy varied between 5 and 14 days (mean 8.6 days). The therapeutic response was rated as cure in 23 (76.6%) patients, with complete disappearance of pretreatment signs and symptoms, and as improvement in seven (23.3%) patients, with amelioration of the pretreatment manifestations. All 52 microorganisms isolated before treatment were eradicated. No adverse effects were reported in 25 (83.3%) patients, whereas the remaining five (16.7%) patients reported mild loose stools with normal bowel motion. There were no abnormal changes in blood count and liver and renal functions following sultamicillin treatment. PMID- 1451928 TI - Relative bio-availability of sultamicillin in healthy volunteers following administration of two tablet formulations. AB - The pharmacokinetics of both ampicillin and sulbactam obtained from a balanced, open two-way crossover study in 20 normal adult volunteers receiving a single 375 mg oral tablet of sultamicillin administered as two different formulations--the original product (Duocid) and a generic formulation that is commercially available in Turkey--were compared. Pharmacokinetic parameters for the two formulations and for both ampicillin and sulbactam were tested for bio equivalence by the two one-sided Student's t-test (80-120% range; P < 0.1). Area under concentration--time curves and maximum concentrations for both components were found to be non-equivalent for the two formulations, the generic formulation having consistently lower mean values. The results were consistent with studies of the in vitro release of sultamicillin from the two tablets. It is concluded that the generic formulation is pharmacokinetically inferior to the original product. PMID- 1451930 TI - An open multicentre study to compare the efficacy and safety of sultamicillin with that of cefuroxime axetil in acute ear nose and throat infections in adults. AB - A total of 110 adults with acute ear, nose and throat infections were treated orally with 750 mg/day (n = 9) or 1500 mg/day (n = 46) sultamicillin, or 500 mg/day (n = 51) or 1000 mg/day (n = 4) cefuroxime axetil for a minimum of 5 days. Variations in dose and duration of treatment were due to severity of symptoms. After treatment with sultamicillin for 8.1 +/- 1.5 days or with cefuroxime axetil for 7.9 +/- 1.6 days, local pain, erythema, exudate, oedema and adenopathies were improved in both treatment groups and all sultamicillin-treated patients were apyretic. All sultamicillin-treated and all but three cefuroxime axetil-treated patients experienced cure or improvement; only one cefuroxime axetil-treated patient discontinued treatment due to treatment failure. Gastrointestinal adverse events occurred in both treatment groups (eight sultamicillin-treated patients and three cefuroxime axetil-treated patients); one patient receiving cefuroxime axetil discontinued treatment due to nausea. Pruritus was reported by one sultamicillin-treated patient. PMID- 1451931 TI - Sultamicillin in the treatment of obstetric and gynaecological infections. AB - A total of 40 adult females were studied suffering from different obstetric and gynaecological infections. In 30 patients two 375 mg sultamicillin tablets were taken twice daily, whereas 10 patients received one 375 mg sultamicillin tablet twice daily. The duration of treatment ranged from 5 to 12 days, with a mean of 6.6 days. Cure or improvement was reported in 35 (87.5%) cases, whereas five (12.5%) patients did not respond to therapy. Of the 61 pathogens isolated before treatment, 56 (91.8%) were eradicated. Clinical tolerability of the therapy was excellent, with no adverse effects being observed in any of the studied patients. The absence of significant differences between the mean values of blood count, hepatic and renal function tests performed before and after treatment confirmed the safety of treatment. It is concluded that sultamicillin is a suitable and useful additional antibiotic therapy for the treatment of obstetric and gynaecological bacterial infections. PMID- 1451932 TI - Attachment--and loss. PMID- 1451933 TI - Childhood physical disability and attachment. PMID- 1451934 TI - Myelomeningocele: a review of the orthopaedic aspects of 206 patients treated from birth with no selection criteria. AB - Two hundred and six consecutive children with spina bifida who have been treated since the first day of life were analysed in terms of walking ability, motor level, orthopaedic deformities, operative procedures and balance deficit. The authors found that: (1) ambulation was quite delayed compared with the normal population; (2) sitting balance was a useful predictor of future walking; (3) almost all patients with quadriceps function were able to walk and were community ambulators; and (4) a significant number of congenital and acquired orthopaedic deformities required surgical intervention. PMID- 1451935 TI - Perceptions of pediatricians' helpfulness: a national study of mothers of young disabled children. AB - A national sample of 503 mothers of young children (up to six years of age) with developmental disabilities was surveyed to determine the extent to which their family pediatricians are helpful in providing information and support. The respondents ranged from lower-middle to upper class, with the mean SES reflective of middle socio-economic status. Their children had a variety of disabilities that qualified them to receive early intervention services. The majority of the mothers found their pediatricians helpful about issues related directly to their child's medical condition. However, few found them helpful with issues relating to the effect of the disability on their child's development, or to their own personal or family needs. PMID- 1451936 TI - The effects of maternal epidural anesthesia on neonatal behavior during the first month. AB - The effects of maternal epidural anesthesia with bupivacaine on the infant's performance on the Neonatal Behavioral Assessment Scale (NBAS) over the first month of life were examined. 20 non-medicated infants were matched for biomedical and demographic variables with 20 infants delivered with bupivacaine epidural anesthesia. The NBAS was administered on days 1, 3, 7 and 28. The epidural group showed poorer performance on the orientation and motor clusters during the first month of life. Epidural mothers reported spending less time with their infants while in the hospital; post hoc analyses showed that they had longer labor, more forceps deliveries and a greater amount of oxytocin. Controlling for the effects of these medical variables, a dose effect was found for the mean orientation and motor cluster scores. The results are discussed in terms of possible effects of the infant's early disorganization on the mother-infant interaction. PMID- 1451937 TI - Fanconi anemia: a model for genetic causes of abnormal brain development. AB - Fanconi anemia is an autosomal recessive disease resulting in bone-marrow failure, phenotypical abnormalities and predisposition to malignancy. The authors reviewed 257 clinical and neuropathology results from the International Fanconi Anemia Registry at The Rockefeller University. Two patients had hydrocephalus and ventriculoperitoneal shunts. Of 15 neuropathology reports, 10 found CNS abnormalities, with the most common--ventriculomegaly--seen in six, two of whom required shunts. Aqueductal stenosis, agenesis of the corpus callosum and septum pellucidum, and holoprosencephaly were found. The authors conclude that neurological derangements are probably more common in Fanconi anemia than previously recognised. Fanconi anemia cells in culture are highly sensitive to oxidative stress and alkylating agents; Fanconi anemia may provide a model for a genetic disorder potentially predisposing to environmental insults. PMID- 1451938 TI - Antecedents and outcome of simple and complex febrile convulsions among Saudi children. AB - Of 215 Saudi children seen with their first febrile convulsion (FC) at the King Khalid University Hospital, Riyadh, between January 1984 and December 1988, the index FC was simple for 133 children and complex for the remaining 82. History of adverse antecedent factors, particularly perinatal asphyxia, birth injuries and pre-existing neurological deficits, were significantly more associated with complex FC, as was occurrence of first FC before the age of 12 months. Recurrence of FCs and development of epilepsy were also more common among the group of children with complex FC. Complex FCs were less benign in the present study population than has been reported in some Western studies. PMID- 1451939 TI - Magnetic resonance imaging in pseudotumor cerebri. AB - The pathophysiology of pseudotumor cerebri is unclear, but may relate to an abnormality in water transport in the brain. The authors performed MR imaging in seven children with pseudotumor cerebri; the signal intensity in the white matter was normal in all patients. These data suggest that periventricular brain water content is not increased markedly in children with pseudotumor cerebri. The authors speculate that this may relate to the establishment of an equilibrium between increased resistance to cerebrospinal fluid outflow and increased brain stiffness, occurring as a consequence of increased cerebral blood-volume and/or interstitial pressure. PMID- 1451940 TI - Epidemiology of headache and childhood migraine in an urban general practice using Ad Hoc, Vahlquist and IHS criteria. AB - In a survey conducted by a UK urban general practice, 98.1 per cent (1083) of the children registered aged three to 11 years took part in an interview. Possible migraine subjects took part in an extended interview, the results of which were recorded using three different sets of diagnostic criteria: Vahlquist, Ad Hoc and International Headache Society. The prevalence of migraine ranged from 3.7 to 4.9 per cent, depending on the criteria used. The prevalence of migraine with aura (1.5 per cent) was similar by all criteria, whereas that for migraine without aura ranged from 2.2 to 3.4 per cent. The prevalence of migraine increased with age. The IHS criteria appeared less sensitive than the Ad Hoc for migraine without aura. Operational criteria using three attacks lasting longer than one hour may be more specific for the diagnosis of migraine in young children. PMID- 1451941 TI - Transient loss of speech followed by dysarthria after removal of posterior fossa tumour. AB - The authors report three children who suffered transient loss of speech during six to eight weeks following removal of a large midline cerebellar tumour. None manifested speech difficulties immediately after surgery, but all developed mutism within 24 to 48 hours. The speech of all children slowly but completely recovered, after a period of severe dysarthria. The re-organization of speech functions is discussed in relation to the functioning of musculature. PMID- 1451942 TI - Pathological left-handedness and preserved function associated with a slowly evolving brain tumor. AB - The authors report the serial neuropsychological evaluations of a patient with acquired left-handedness who had a massive brain tumor that infiltrated the entire temporal and posterior parietal lobes of the left hemisphere. Although the patient had pre-operative impairment of non-verbal memory, follow-up assessment 31 and 66 months after the tumor was resected revealed cognitive functions to be in the high-average to superior range. This case demonstrates the sparing of neuropsychological functions that can be seen with a slowly evolving lesion. The authors suggest that such functional sparing may be due to transfer of function rather than to the residual function of tumor-infiltrated neuronal tissue. Possible mediators of functional preservation include slow lesion growth, the patient's youth at disease onset and the large size of the lesion. PMID- 1451943 TI - 'Identification of neurodevelopmental abnormality at four and eight months by the movement assessment of infants'. PMID- 1451945 TI - The fiftieth anniversary of hypoglycaemic sulphonamides. How did the mother compound work? PMID- 1451944 TI - Magnetic resonance imaging of the kidney in type 1 (insulin-dependent) diabetes mellitus. AB - Reductions in the physiological cortical to medullary signal intensity ratio are found in magnetic resonance scans of the kidney in non-diabetic glomerular disease. Whether this abnormality can also characterise patients with Type 1 (insulin-dependent) diabetes mellitus and nephropathy is not known. We measured the cortical to medullary signal intensity ratio in magnetic resonance images of the kidney in 34 patients with Type 1 diabetes (ten with either clinical proteinuria or raised serum creatinine or both, nine with microalbuminuria, seven with normal urinary albumin excretion and long duration of diabetes and eight with Type 1 diabetes of short duration). The cortical to medullary signal intensity ratio showed a trend to cluster at lower values in the normoalbuminuric patients with normal serum creatinine rather than in the nine healthy individuals, independent of Type 1 diabetes duration (1.47 +/- 0.06 and 1.41 +/- 0.13 vs 1.63 +/- 0.16; five groups Scheffe F-test p = 0.05-0.1). Among the Type 1 diabetic patients, significant reductions in the cortical to medullary signal intensity ratio characterised overt nephropathy (1.19 +/- 0.15, p less than 0.05 vs all groups), but not microalbuminuria (1.47 +/- 0.13, p = NS), concomitantly with low glomerular filtration rate and elevated fractional excretion of uric acid, but independent of glycaemic control. The determinants of the renal cortical to medullary signal intensity ratio in Type 1 diabetes are uncertain. Reductions in the cortical to medullary signal intensity ratio may be a late finding in diabetic nephropathy, and parallel the accompanying impairment in kidney haemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451946 TI - Protective effect of vitamin E supplementation on increased thermal stability of collagen in diabetic rats. AB - Products similar to non-enzymatic glycation end products are known to arise from the interactions between proteins and lipid peroxides in vitro. In this study, we assessed the effect of vitamin E, which possibly modifies lipid peroxide, on advanced glycation end products or similar products in vivo by measuring the fluorescence and thermal rupture time of tail tendon collagen in streptozotocin induced diabetic rats. The diabetic rats and non-diabetic rats were fed a vitamin E supplemented diet, and a control diet starting 3 days after the streptozotocin injection. After the 4-week treatment, the serum lipid peroxide levels expressed as thiobarbituric acid reactants in the diabetic rats on control diet (15.9 +/- 2.6 mumol/l[SEM]) were significantly (p less than 0.05) higher than in the non diabetic rats (7.9 +/- 1.3 mumol/l on control diet and 3.3 +/- 0.4 mumol/l on supplemented diet), but the levels in the diabetic rats on supplemented diet (7.9 +/- 2.3 mumol/l) were reduced to the normal levels. No significant differences were found in serum glucose and glycated haemoglobin levels within the diabetic rats on control and supplemented diets. Both the fluorescence and thermal rupture time of collagen were significantly (p less than 0.05) increased in the diabetic rats on both diets compared with those in the corresponding non-diabetic rats. Although there was no significant difference in the collagen-linked fluorescence within the diabetic rats on control and supplemented diets, the thermal rupture time was significantly (p less than 0.01) shortened with supplemented diet (10.8 +/- 0.7 min on supplemented diet vs 15.0 +/- 0.7 min on control diet).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451947 TI - Insulin secretion by rat islet isografts of a defined endocrine volume after transplantation to three different sites. AB - We have analysed the graft function of rat islet isografts of identical and well defined endocrine volumes after transplantation to three different sites (kidney, liver and spleen). Graft endocrine mass was determined by measuring the total islet volume prior to transplantation and was chosen to be similar to the endocrine volume in the normal adult rat pancreas. Graft function was tested in unanaesthetized, unstressed rats by the responses to glucose infusion and to a meal. All transplanted animals returned to normoglycaemia within one week after transplantation. At one month, basal glucose and insulin levels were similar to controls in rats with grafts to the spleen, but higher in rats with grafts to the kidney or liver. Irrespective of the transplantation site, recipients had higher glucose and lower insulin levels than controls in response to glucose infusion, but in response to a meal these differences from normal were less obvious. Finally, recipients showed both an acute insulin response to glucose infusion as well as a pre-absorptive insulin release after food ingestion, irrespective of the transplantation site. Our findings indicate that the insulin response to glucose infusion and to a meal is quantitatively reduced, but qualitatively intact after transplantation to the kidney, liver or spleen. PMID- 1451948 TI - Role of infiltrating T cells for impaired glucose metabolism in pancreatic islets isolated from non-obese diabetic mice. AB - Pancreatic islets isolated from non-obese diabetic (NOD) mice, all of which have insulitis, exhibit an impaired glucose metabolism. In order to investigate the role of infiltrating lymphocytes for this altered metabolism, we injected 12- to 13-week-old female NOD mice with monoclonal antibodies directed against either the alpha beta-T cell receptor, CD4+ or CD8+ T cells. Control NOD mice were injected with normal rat IgG or with the vehicle (phosphate buffered saline) alone. Injection of the three different monoclonal antibodies markedly reduced the mononuclear cell infiltration. An intravenous glucose tolerance test showed no differences between the groups. Islet insulin release in response to glucose was similar in all groups. In contrast, islets isolated from the control NOD mice with insulitis showed a high basal (1.7 mmol/l glucose) glucose oxidation rate and a small increase in the glucose oxidation rate in response to a high glucose concentration (16.7 mmol/l glucose). The monoclonal antibodies counteracted the elevated basal glucose oxidation rate of the islets. Parallel studies of stimulated mononuclear cells suggested that the contribution of glucose oxidized by islet-infiltrating lymphocytes could only partially explain the observed alterations in NOD mouse islet metabolism. Culture of islets obtained from NOD mice in the presence of the cytokine interleukin-1 beta induced a similar pattern of glucose metabolism as seen earlier in IgG or phosphate-buffered saline treated control NOD mice. In conclusion, alterations in the glucose oxidation rates seem to be an early sign of disturbance in islets isolated from NOD mice. These early alterations in glucose metabolism can be reversed in vivo by monoclonal antibodies directed against effector lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451949 TI - Acute actions of insulin-like growth factor II on glucose metabolism in adult rats. AB - The metabolic potency of recombinant human insulin-like growth factor II was studied in anaesthetized adult rats by obtaining dose-response curves for the hypoglycaemic action and for the stimulation of glucose metabolism during euglycaemic clamping. Compared to insulin, about 50 times higher doses of insulin like growth factor II were required to result in identical in vivo responses, with half-maximally effective serum concentrations for the stimulation of glucose disposal during clamp studies of about 0.8 and 50 pmol/ml, respectively. A similar difference in potency was observed for the dose-dependent stimulatory actions on glucose metabolism in individual target tissues. Half-maximally effective serum concentrations in the range of 0.8 to 3.0 pmol/ml for insulin and of 40 to 70 pmol/ml for insulin-like growth factor II were seen to be required for 2-deoxyglucose uptake, glycogen formation in skeletal muscle and lipogenesis in epididymal fat. Maximal responses were identical with both peptides. These data suggest that in vivo acute metabolic actions of insulin-like growth factor II on carbohydrate metabolism occurred through insulin receptors. PMID- 1451950 TI - Persistent reduction of pancreatic beta-cell mass after a limited period of protein-energy malnutrition in the young rat. AB - Kwashiorkor, the human disease of protein-energy malnutrition, has been implicated in the aetiology of malnutrition-related diabetes mellitus, a form of diabetes not uncommon in developing countries. We have previously demonstrated that temporary protein-energy malnutrition in young rats causes a persisting impairment of insulin secretion. The present study investigates whether this secretory deficiency is accompanied by structural alterations of the endocrine pancreas. Three-week-old rats were weaned onto semi-synthetic diets containing either 15% or 5% protein and these diets were maintained for 3 weeks. From 6 weeks of age all rats were fed a commercial chow containing 18% protein. The endocrine pancreas was investigated by light and electron microscopic morphometry at 3, 6 and 12 weeks of age. In rats not subjected to protein-energy malnutrition there was a progressive increase, with age, of total pancreatic Beta-cell weight and individual Beta-cell size. In 6-week-old rats fed the low protein diet total pancreatic Beta-cell weight and individual Beta-cell size were diminished. In 12 week-old rats previously fed the low protein diet total Beta-cell weight remained lower compared to control rats. It is concluded that protein-energy malnutrition early in life may result in a diminished reserve for insulin production. This may predispose to glucose intolerance or even diabetes in situations with an increased insulin demand. PMID- 1451951 TI - Effects of aminoguanidine on peripheral nerve function and polyol pathway metabolites in streptozotocin-diabetic rats. AB - The effect of 2 months aminoguanidine treatment on nerve conduction abnormalities was studied in streptozotocin-diabetic rats. Treatment with aminoguanidine from the induction of diabetes mellitus prevented a 22% decrease in sciatic motor nerve conduction velocity (p less than 0.001), and a 10% deficit in sensory saphenous conduction velocity (p less than 0.01). There was a 49% increase in resistance of sciatic nerve to hypoxic conduction failure in vitro. This was not significantly affected by aminoguanidine treatment. Sciatic nerve polyol pathway metabolites, sorbitol and fructose, were elevated 10-fold by diabetes (p less than 0.001). Myo-inositol levels were 18% decreased by diabetes. Aminoguanidine treatment had no significant effect on sorbitol, fructose or myo-inositol levels. Aminoguanidine has been identified as both an inhibitor of the formation of advanced glycation end products, and an aldose reductase inhibitor. The data suggest that beneficial actions on nerve function do not depend on the latter property. They support the notion that advanced glycation end products contribute to the aetiology of early diabetic neuropathy, possibly acting via a vascular mechanism, and that aminoguanidine treatment may have therapeutic applications. PMID- 1451952 TI - Life table analysis of the risk of type 1 (insulin-dependent) diabetes mellitus in siblings according to islet cell antibodies and HLA markers. An 8-year prospective study. AB - To determine whether genetic markers can improve the predictive value of islet cell antibodies for development of Type 1 (insulin-dependent) diabetes mellitus, 536 siblings aged 2-29 years were consecutively enrolled in a 8-year prospective survey. The risk of developing diabetes was estimated, using life-table methods, by years of follow-up and age, according to genetic factors (shared HLA haplotypes, DR antigens, C4 allotypes) and islet cell antibody status. Fifteen siblings (2.8%) developed Type 1 diabetes during the study period (risk 4.4% after 8 years, 4% by age 22 years). DR3,4 heterozygosity identified higher risk (16% after 8 years, 12% by age 22 years, p less than 10(-5)) than HLA-identity (10% and 7%, respectively, p less than 0.01); risks for DR3 or DR4 positive and for haplo-identical siblings were low (4%, 3% and 4.4%, respectively, NS). C4BQO also conferred significant risk (11% vs 3% in non-C4BQO siblings, p less than 0.01). The predictive value of genetic markers alone was poor (12% for DR3,4, 7% for HLA-identity, 9% for C4BQO) compared with that of islet cell antibody levels greater than 4 Juvenile Diabetes Foundation units (41%, risk 56% after 8 years, p less than 10(-7)). HLA markers significantly contributed to risk prediction in combination with islet cell antibodies: islet cell antibody-positive DR3,4+ subjects had the highest risk (70% after 8 years, predictive value 58%, p less than 10(-7)) compared with islet cell antibody-positive DR3,4- (37% and 20%, respectively) and islet cell antibody-negative DR3,4+ (5% and 3.6%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451953 TI - Reproducibility of glycaemic thresholds for activation of counterregulatory hormones and hypoglycaemic symptoms in healthy subjects. AB - Nine healthy subjects were studied on two separate occasions, at least two weeks apart, using the glucose clamp technique to produce a gradual hypoglycaemia. Glucose thresholds for neuroendocrine and symptom responses varied up to 1.5 mmol/l between subjects. There was a significant correlation between individual glucose thresholds on day 1 and 2 for adrenaline (p = 0.0008), growth hormone (p = 0.007) and pancreatic polypeptide (p = 0.02), and for autonomic (p = 0.018) and neuroglycopoenic (p = 0.023) symptoms, whereas no significant correlations were found for glucagon and cortisol. The mean intra-individual differences in glucose thresholds between day 1 and 2 were 0.22 mmol/l for the hormones and 0.25 mmol/l for the symptoms. We conclude that healthy subjects differ in hypoglycaemic thresholds, and that the difference reflects individual variation. PMID- 1451954 TI - Factors associated with basal metabolic rate in patients with type 2 (non-insulin dependent) diabetes mellitus. AB - To examine determinants of basal metabolic rate we studied 66 Type 2 (non-insulin dependent) diabetic and 24 healthy age- and weight-matched control subjects with indirect calorimetry and infusion of [3H-3-] glucose. Eight Type 2 diabetic patients were re-studied after a period of insulin therapy. Basal metabolic rate was higher in Type 2 diabetic patients than in control subjects (102.8 +/- 1.9 J.kg LBM-1.min-1 vs 90.7 +/- 2.8 J.kg LBM-1.min-1; p less than 0.01) and decreased significantly with insulin therapy (p less than 0.01). The basal rate of hepatic glucose production was higher in Type 2 diabetic patients than in control subjects (1044.0 +/- 29.9 vs 789.3 +/- 41.7 mumol/min; p less than 0.001) and decreased after insulin therapy (p less than 0.01). Hepatic glucose production correlated positively with basal metabolic rate both in Type 2 diabetic patients (r = 0.49; p less than 0.001) and in control subjects (r = 0.50; p less than 0.05). Lipid oxidation was increased in Type 2 diabetic patients compared with control subjects (1.68 +/- 0.05 vs 1.37 +/- 0.08 mumol.kg LBM-1.min-1; p less than 0.01) and decreased significantly after insulin therapy (p less than 0.05). The rate of lipid oxidation correlated positively with basal metabolic rate both in Type 2 diabetic patients (r = 0.36; p less than 0.01) and in control subjects (r = 0.51; p less than 0.01). These data demonstrate that basal metabolic rate, rates of hepatic glucose production and lipid oxidation are interrelated in Type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451955 TI - Oral contraceptive use and the risk of type 2 (non-insulin-dependent) diabetes mellitus in a large prospective study of women. AB - We examined the association between oral contraceptive use and incidence of Type 2 (non-insulin-dependent) diabetes mellitus among 115117 female nurses free of diabetes, cardiovascular disease and cancer in 1976 and followed-up for 12 years. During 1237440 person years of follow-up, 2276 women who provided information on oral contraceptive use were clinically diagnosed with Type 2 diabetes. Women who used oral contraceptives in the past had only a slight and marginally increased relative risk of 1.10 (95% confidence interval 1.01, 1.21) compared to those women who had never used oral contraceptives after controlling for known risk factors of disease. We found no evidence of increased risk with longer duration of use or with shorter interval since last use. Current users did not have an increased risk of Type 2 diabetes (relative risk = 0.86, 95% confidence interval 0.46, 1.61) when compared to women who had never used the drug. There was no effect modification by obesity, family history of diabetes, or physical activity. These data suggest that past or current oral contraceptive use does not substantially influence subsequent risk of Type 2 diabetes. PMID- 1451956 TI - Trends in mortality from diabetes mellitus in Taiwan, 1960-1988. AB - The increasing trends of mortality from diabetes mellitus in Taiwan are becoming a public health concern. The age-adjusted death rate for diabetes was 3.7 per 100,000 population in 1960, which increased to 23.2 per 100,000 in 1988, a 6.3 fold increase over the past 30 years. The mortality data for diabetes in Taiwan from 1960 to 1988 for both sexes are presented and analysed using an age-period cohort model in order to gain a better understanding of the possible determinants of the time trends of this disease. Steeply increasing trends which are particularly prominent in the elderly are found in the periods studied. Females and urban dwellers demonstrated greater risks for developing the disease. Significant cohort effects were found which peaked in the birth-cohort 1910-1917. This declined thereafter for females but has levelled since then for males. Further study is necessary to assess the aetiological implications of diet and urbanization on time trends of diabetes. PMID- 1451957 TI - An increased level of antibodies to beta-lactoglobulin is a risk determinant for early-onset type 1 (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow's milk. AB - Using a case-control design we have studied whether antibodies to cow's milk proteins are risk determinants for childhood-onset Type 1 (insulin-dependent) diabetes mellitus independent of early exposure to cow's milk formula and islet cell antibodies. Sera from 116 recent-onset diabetic children and 112 age- and sex-matched control children were analysed for cow's milk protein IgA, IgG and IgM antibodies, beta-lactoglobulin IgA and IgM antibodies and islet cell antibodies. The titres were compared to questionnaire data on duration of breast feeding and introduction of formula feeding. Most antibody levels tended to be increased among diabetic compared to control children. This was statistically significant for cow's milk protein IgA antibodies (p less than 0.001) and beta lactoglobulin IgA antibodies (p less than 0.01) as well as for islet cell antibody-positivity which was found among 92% of the diabetic and 3% of control children. The differences in cow's milk protein antibodies as well as beta lactoglobulin antibodies were more pronounced among children with an early onset of Type 1 diabetes. Breast-feeding duration was significantly inversely related to the log of beta-lactoglobulin IgG (r = -0.16, p = 0.04) and the log of cow's milk protein IgA antibodies (r = -0.17, p less than 0.001). A positive correlation was found between formula feeding and the logarithm of beta lactoglobulin IgG antibodies (r = 0.22, p = 0.01) and the log of cow's milk protein IgA antibodies (r = 0.16, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451958 TI - Disease-associated anti-bovine serum albumin antibodies in type 1 (insulin dependent) diabetes mellitus are detected by particle concentration fluoroimmunoassay, and not by enzyme linked immunoassay. AB - We recently developed a particle concentration fluoroimmunoassay for the measurement of serum antibodies to bovine serum albumin in patients with Type 1 (insulin-dependent) diabetes mellitus. We observed elevated IgG-anti-bovine serum albumin antibodies in 100% of newly-diagnosed diabetic children and in 2.5% of matched control children. Here we compare the fluoroimmunoassay and the more commonly available enzyme linked immunoassay technique, exchanging coded serum samples from 40 newly-diagnosed diabetic children and 179 control children between two laboratories. Particle concentration fluoroimmunoassay detected elevated IgG-anti-bovine serum albumin antibodies in all diabetic children, enzyme immunoassay in 25% (p less than 0.0001). Fluoroimmunoassay detected elevated levels in 2.2% and enzyme immunoassay in 10% of control children (p less than 0.002). Elevated IgA-anti-bovine serum albumin antibodies in patients were slightly more often detected by fluoroimmunoassay than by enzyme immunoassay, while in control children enzyme immunoassays detected elevated levels three times more often (p less than 0.01). Values measured in either assay showed overall no correlation in either patient (IgG:rs = 0.28; IgA:rs = 0.11) or control sera (IgG:rs = 0.02; IgA:rs = -0.05). Fluoroimmunoassay for IgG was 100% disease-sensitive (enzyme immunoassay: 25%, p less than 0.0001) and more disease specific (IgG; p less than 0.02). Our findings demonstrate that these assay techniques detected distinct subsets of anti-bovine serum albumin antibodies with little (IgG) or some (IgA) overlap. In fluoroimmunoassay procedures, antigen:antibody binding occurs within 1-2 min while hours are allowed in an enzyme immunoassay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451959 TI - Increases in plasma lysosomal enzymes in type 1 (insulin-dependent) diabetes mellitus: relationship to diabetic complications and glycaemic control. AB - Lysosomal enzymes degrade membrane glycoconjugates, and increased circulating enzyme activity may be an important mechanism in the pathogenesis of diabetic microangiopathy. We have assayed a profile of seven lysosomal enzyme activities (nmol.h-1.ml-1) in platelet-free plasma from 54 Type 1 (insulin-dependent) diabetic subjects (median age 31 years) and 42 matched normal control subjects. A significant increase in median (interquartile range) enzyme activity was measured in diabetic compared to control subjects for beta-D-glucuronidase, 121 (97.7-171) vs 88.8 (62.8-113), p less than 0.001; beta-D-Nacetylglucosaminidase, 693 (568 799) vs 568 (462-686), p less than 0.001; alpha-D-mannosidase, 23.8 (16.7-28.9) vs 14.5 (10.1-20.0), p less than 0.001; and beta-D-galactosidase, 6.94 (6.11 9.99) vs 6.66 (4.78-8.33), p less than 0.04. In contrast, alpha-L-fucosidase, alpha-D-galactosidase and beta-D-mannosidase activities were similar in diabetic and control subjects. None of the enzyme activities differed significantly (p less than 0.05) between 24 diabetic patients with clinical complications and 30 complication-free diabetic patients with similar glycaemic control which does not support the hypothesis that enzyme increases in diabetes arise simply by leakage from damaged tissues. In the diabetic subjects HbA1, median (interquartile range) 9.10 (7.40-10.60), was significantly related to beta-D-glucuronidase (rs = 0.56, p less than 0.001) and beta-D-Nacetylglucosaminidase (rs = 0.55, p less than 0.001). We have therefore demonstrated in diabetic subjects an increase in certain lysosomal glycosidases, that correlates with glycaemic control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1451960 TI - The small heat shock protein hsp25 is accumulated in P19 embryonal carcinoma cells and embryonic stem cells of line BLC6 during differentiation. AB - Murine embryonal carcinoma and embryonic stem cell lines were investigated with regard to the occurrence of the small heat shock protein hsp25 during cell growth and differentiation. In the embryonal carcinoma cell line F9 considerable constitutive levels of hsp25 were observed which could be slightly increased by treatment with retinoic acid. No hsp25 was found, however, in the embryonal carcinoma cell line PCC4. When analyzing the pluripotent embryonal carcinoma cell line P19 and the pluripotent embryonic stem cell line BLC6, both characterized by high differentiation capacity, no hsp25 was observed under cell culture conditions maintaining the undifferentiated state. Induction of differentiation caused by prolonged cell culture, retinoic acid treatment, or embryoid body formation, however, resulted in an increase of the level of hsp25. The finding that hsp25 is accumulated in a differentiation-dependent manner suggests that this protein is associated with processes involved in differentiation. Therefore, hsp25 can be regarded as a marker of differentiation in the investigated embryonal carcinoma cell line P19 and the embryonic stem cell line BLC6. PMID- 1451961 TI - The hamster cheek pouch as a convenient ectopic site for studies of uterine morphogenesis and endocrine responsiveness. AB - The Syrian hamster cheek pouch was evaluated as a convenient transplantation site for studies of estrogen-dependent uterine growth and morphogenesis. At one month of age, hosts were either ovariectomized (Ovex) or ovariectomized and estrogen implanted (Ovex+E2), and at the same time the uterus from a 7-day old untreated donor was transplanted into the host's right cheek pouch. Periodic inspection (by simple eversion of the pouch) revealed viable transplants in the majority of hosts for both groups, and clear evidence of estrogen-dependent transplant growth that continued for at least 9 months. At that time, weight of the transplanted uterus was comparable to that of a given host's own in situ uterus, but uteri at both sites weighed six to eightfold more in Ovex+E2 hosts than in Ovex hosts. Histological analysis also revealed similar degrees of endometrial atrophy in Ovex hosts and hypertrophy/hyperplasia in Ovex+E2 hosts for both in situ and transplanted uteri. Furthermore, while only scant and rudimentary endometrial glands developed in both in situ and transplanted uteri within Ovex hosts, uteri at both sites within the Ovex+E2 hosts were riddled with cystic glandular structures and exhibited marked leukocytic infiltration. These data demonstrate that neonatal uteri transplanted to the hamster cheek pouch will grow, differentiate and follow an endocrine-responsive morphogenetic program that is quantitatively and qualitatively consistent with that of the host's in situ uterus. Lastly, we were able to cleanly separate epithelium from the stroma of 5 day old hamster uteri, reassociate the two tissues in vitro, transplant the recombinants into cheek pouches of adult female hamsters and subsequently observe growth and maintenance of a generally normal uterine morphology and differentiated function. PMID- 1451962 TI - Immunohistochemical study of secretory proteins in the developing human exocrine pancreas. AB - We have studied, by immunohistochemical methods using specific antisera, the development of three glycoproteins of human pancreatic secretion: lipase, carboxyl ester hydrolase (CEH) and the P19 protein (precursor of the non glycosylated protein X or "pancreatic thread/stone protein"). We have compared their development to that of trypsinogens (Tgs) and chymotrypsinogen A (ChTgA), as well as to that of FAP (feto acinar pancreatic protein), a glycoprotein associated with the differentiation of human pancreas. Our studies show the characteristic appearance and development of lipase, the immunoreactivity of which appears later (at the 21st week of pregnancy) than it does for Tgs and ChTg (at the 16th week of pregnancy). Moreover, the lipase labelling is first observed in a few acini dispersed in the pancreas and then spreads out progressively to be present in all the acini after the age of 15 days. By contrast, as soon as they appear, Tgs and ChTg are observed uniformly in all acinar cells. The intensities of the lipase, Tgs and ChTg labellings increase greatly at birth. The ontogenesis of CEH does not follow that of lipase but that of Tgs and ChTg. The ontogenesis of P19 is parallel to that of Tgs. As previously observed, FAP presents a maximal immunoreactivity at the 24th-27th weeks of pregnancy, which decreases slowly up until birth. PMID- 1451964 TI - The future of gastrointestinal practice and education: self-regulation or governmental control? PMID- 1451963 TI - Modulation of differentiation markers in human choriocarcinoma cells by extracellular matrix: on the role of a three-dimensional matrix structure. AB - During spontaneous or chemically induced differentiation human choriocarcinoma cells express typical characteristics of the normal differentiating trophoblast: 1) increased production of peptide and steroid hormones (chorionic gonadotropin, placental lactogen, estrogens, progesterone); 2) increased activity of cellular alkaline phosphatase; 3) morphological transition from cytotrophoblast to syncytiotrophoblast-like cells; and 4) arrested cell proliferation. Since the extracellular matrix is known to control gene expression we have examined the effects of different substrates composed of matrix macromolecules on the differentiation of BeWo choriocarcinoma cells. Matrices tested were: fibronectin, laminin, collagens type I and type IV, the basement membrane-like complex matrix Matrigel, and a complex matrix extracted from human term placenta. Irrespective of the type of molecule(s), it was consistently found that, whenever the matrix molecules were presented as three-dimensional structures (as opposed to protein coatings on tissue culture plastic) the response of affected differentiation markers monitored was highly pronounced. Morphology was changed from monolayers to rounded colonies, cell proliferation was reduced, and the secretion of chorionic gonadotropin was increased up to tenfold. Heterogeneous effects were observed on progesterone secretion and on the activity of cellular alkaline phosphatase. Cell adhesion to matrix molecules, however, did not depend on the structure of the matrix. This study demonstrates that gene expression in these tumor cells can be modified by extracellular matrix and highlights that not only the presence of effector molecules in the matrix but also the three-dimensional structure of the matrix is important for the induction of differentiation. PMID- 1451965 TI - Presentation of the Julius Friedenwald Medal to Basil I. Hirschowitz, M.D. PMID- 1451966 TI - Predictors of outcome in patients with achalasia treated by pneumatic dilation. AB - This prospective study investigates whether the effect of pneumatic dilation in patients with achalasia can be predicted on the basis of patient characteristics, type of treatment, or results of postdilation investigations. Over a period of 10 years, 54 consecutive patients with newly diagnosed achalasia were treated with pneumatic dilation and underwent pretreatment and posttreatment manometric, radiographic, and scintigraphic investigations. They were followed up every 2 years until the fall of 1991. Among the factors evaluated in the initial examination, only young age adversely affected outcome (P < 0.05). With the exception of the diameter of the dilating balloon, the treatment characteristics had a low predictive value. Postdilation lower esophageal sphincter pressure was the single most valuable factor for predicting the long-term clinical response (P < 0.0005). However, patients with high sphincter pressures and poor treatment results benefited from repeated dilations by having progressively longer remissions. It is concluded that young patients are poor candidates for pneumatic dilation, that treatment should be aimed at near complete inflation of the dilating bag, and that postdilation sphincter pressure may guide further treatment. PMID- 1451967 TI - Patchy expression of lactase protein in adult rabbit and rat intestine. AB - Enzymatic and immunohistological analyses of lactase were performed at different stages of development and within different regions of the small intestine of the rabbit and rat. As previously reported, there seems to be a sharp decline of lactase activity on weaning but variable and higher levels of activity are seen in adult animals. Two monoclonal antibodies to rat lactase were available to study the protein in rats. Four monoclonal antibodies to human lactase were shown to cross-react with rabbit lactase and used for the rabbit studies. Immunohistological analysis of small intestine of adult rabbits and rats showed residual lactase protein within the enterocytes throughout the small intestine. In the middle of the small intestine (lower jejunum, upper ileum), uniform staining of the brush border was observed. In the proximal and distal regions, a patchy pattern of staining was observed. This pattern, which resembles that observed in adult hypolactasic humans, indicates an underlying heterogeneity of enterocyte differentiation. PMID- 1451968 TI - Activation of human phagocyte oxidative metabolism by Helicobacter pylori. AB - A characteristic feature of chronic antral gastritis is the abundant inflammatory response in close association with Helicobacter pylori, but the immunopathological mechanisms of tissue damage are unknown. Because reactive oxygen radicals have been implicated in the tissue damage of other chronic inflammatory disorders, we investigated the potential ability of H. pylori sonicate to influence the oxidative burst responsiveness of human polymorphonuclear leukocytes and monocytes. For both cell types, a dose-dependent stimulation in a chemiluminescence system was observed. Furthermore, preincubation in sonicate caused a marked priming of the cells to subsequent stimulation with the oligopeptide N-f-methionyl-leucyl-phenylalanine and phorbol myristate-acetate. The sonicate activity was nondialysable, completely destroyed by proteinase and resistant to heat treatment. However, dialysis of boiled sonicate significantly reduced the activity, suggesting the breakdown of a larger molecule(s) to smaller fragments still biologically active. Preliminary experiments suggest that the activity is 25-35 kilodaltons. The demonstration of a protein with stimulatory activity for production of reactive oxygen radicals by human phagocytes may contribute to the understanding of the immunopathology associated with H. pylori infection. PMID- 1451969 TI - Adaptive changes in the pyloric motor response to intraduodenal dextrose in normal subjects. AB - Gastric emptying of glucose is faster after dietary supplementation of glucose, suggesting specific adaptation to changes in nutrient intake. In the present study, the effects of a continuous long-term (0-120-minute) and two short-term (0 20- and 80-100-minute) intraduodenal infusions of dextrose (2.4 kcal/min) on antropyloroduodenal motility and blood glucose, plasma gastric inhibitory polypeptide, and insulin concentrations were evaluated in nine volunteers. In four volunteers, an intraduodenal infusion of triglyceride (2.4 kcal/min) was administered immediately after the long-term dextrose infusion. The long-term dextrose infusion initially increased isolated pyloric pressure waves (IPPWs) and basal pyloric pressure (P < 0.05 for both), but after about 30 minutes IPPWs and basal pyloric pressure decreased and returned to baseline within 80 minutes. Each short-term infusion increased IPPWs and basal pyloric pressure (P < 0.05 for both). Antral pressure waves remained suppressed during the long-term dextrose infusion. Intraduodenal triglyceride increased IPPWs and basal pyloric pressure (P < 0.05 for both). The long-term dextrose infusion was associated with a sustained increase, and both short-term dextrose infusions were associated with peaks in glucose, insulin, and gastric inhibitory polypeptide levels. There was no significant relationship between biochemical measurements and antropyloroduodenal motility. It is concluded that specific adaptive changes occur rapidly in the phasic and tonic pyloric motor response, but not the antral motor response, to intraduodenal dextrose. PMID- 1451970 TI - Uremia increases gastric mucosal permeability and acid back-diffusion injury in the rat. AB - The possibility that chronic uremia renders the gastric mucosa more susceptible to acid injury was investigated. A rat model of chronic renal failure was induced by subtotal nephrectomy. [H+] back-diffusion across the mucosa, following intragastric perfusion of 0.15N HCl or 15% ethanol in 0.15N HCl, was significantly greater in uremic than in sham-operated rats. Gastric mucous gel thickness and transmural potential difference were significantly lower in rats with renal insufficiency. Furthermore, a significantly greater acidification rate of the surface epithelial cells was found in uremic rats than in sham-operated rats during superfusion with pH 1.7 buffer. Intragastric administration of acidified ethanol or aspirin solutions markedly increased gastric mucosal blood flow (68% and 89% respectively) in the sham-operated group producing mild injury, in contrast to uremic rats, where a lesser increase in mucosal blood flow (7% and 14% respectively) was associated with more pronounced mucosal injury. It was concluded that enhanced susceptibility to acid injury in uremia is due to a reduction of function of pre-epithelial, epithelial, and postepithelial elements of the gastric mucosal barrier. PMID- 1451971 TI - Differential induction of major histocompatibility complex molecules on mouse intestine by bacterial colonization. AB - The aim of this study was to determine what factors induce major histocompatibility complex (MHC) molecules on the mouse small intestinal epithelium by using immunohistochemical methods. In germ-free mice, although MHC class I molecules such as H-2K and thymus leukemia antigen (TLa) were expressed on the small intestinal epithelium, class II molecules were absent. The introduction of microorganisms into germ-free mice induced characteristic MHC molecules on the small intestinal epithelial cells. The I-A molecule was induced on the villus tip and crypt epithelial cells 7 days after conventionalization, and the I-E molecule was induced on the mid villus and crypt epithelial cells 14 days after conventionalization. The staining intensity of the H-2K molecules was increased 4 days after conventionalization. In contrast, TLa did not change during conventionalization of germ-free mice. These results suggest that the expression of MHC molecules, except for the TLa, is greatly dependent on the presence of intestinal microorganisms. PMID- 1451972 TI - Subepithelial collagen table thickness in colon specimens from patients with microscopic colitis and collagenous colitis. AB - Microscopic colitis and collagenous colitis are similar conditions that are differentiated by the presence or absence of subepithelial collagen table thickening. To better understand the relationship between these two disorders and the role of collagen table thickening in the pathogenesis of diarrhea, colonic mucosal biopsy specimens from 24 patients with microscopic or collagenous colitis and 9 control subjects were analyzed using a computer-assisted morphometric method to evaluate the average thickness of the subepithelial collagen table. The collagen table thickness in colitis patients taken together formed a multimodal rather than a unimodal distribution. There was no tendency for collagen table thickening to increase with age or with duration of symptoms. In general, the types and distribution of inflammatory cells were similar in patients with normal and thickened collagen tables. Stool weight correlated with lamina propria cellularity but not with collagen table thickening. The multimodal distribution of collagen table thickening and the lack of correlation with age, duration of symptoms, or inflammation suggest that microscopic colitis and collagenous colitis are discrete conditions, although the inflammatory changes in the two conditions are similar. Moreover, because stool weight correlates with lamina propria cellularity but not with collagen table thickening, diarrhea probably is caused by the inflammatory changes and not by collagen table thickening per se. PMID- 1451973 TI - Stimulation of acid secretion increases the gastric gland luminal pressure in the rat. AB - The gastric mucosal gland luminal pressure was measured in vivo with a pressure sensitive microelectrode technique (servo-null) in anesthetized rats. A microelectrode was inserted into a gland lumen by means of a micromanipulator at an angle of 30 degrees to the mucosal surface. Acid secretion was estimated by measuring the pH in the solution covering the mucosa. During control conditions, when the mucosa was secreting acid spontaneously, gland luminal pressure was 12.3 +/- 1.2 mm Hg. At about 9 minutes after starting pentagastrin administration, the luminal pressure stabilized at 17.2 +/- 1.7 mm Hg. In the rats given impromidine (500 micrograms.kg-1.h-1) luminal pressure gradually increased (during 9-10 minutes) from a control level of 9.0 +/- 1.9 to 17.3 +/- 2.6 mm Hg. During the majority of experiments, the luminal pressure oscillated at 3-7 cycles per minute. The results show that intraluminal pressure increases during stimulated acid secretion, indicating that a resistance to the volume secretion exists in the upper part of the gastric crypts. This hydrostatic pressure may well be the driving force for creating channels for acid and pepsin to cross the mucus layer covering the mucosal surface. PMID- 1451974 TI - Sex differences in gastric alcohol dehydrogenase activity in Sprague-Dawley rats. AB - The effects of sex differences and of fasting on gastric alcohol dehydrogenase activity were determined in Sprague-Dawley rats. Gastric alcohol dehydrogenase activity and enzyme protein levels were higher in female than in male rats. Ovariectomy and orchiectomy had no effect on alcohol dehydrogenase and did not alter the sex difference in enzyme activity. Fasting decreased the enzyme activity more in female than in male rats, abolishing the sex difference. Serum gastrin levels measured in female rats decreased on fasting and returned to normal levels within 24 hours of refeeding. Short- and long-term administration of pentagastrin to fasted and fed female rats did not affect the enzyme activity or enzyme protein level, except for a transient increase in enzyme activity but not in enzyme protein level 12 hours after administration to fasted fats. Omeprazole, which increased serum gastrin levels and decreased enzyme activity but not enzyme protein levels, was found to be a competitive inhibitor of the enzyme with a Ki of 0.40 mmol/L. The mechanisms for the sex differences and changes with fasting in rat gastric alcohol dehydrogenase activity remain unknown. PMID- 1451975 TI - Human gastric myoelectric activity and gastric emptying following gastric surgery and with pacing. AB - Postoperative gastric myoelectric activity, gastric emptying, and clinical course were correlated in 17 patients at high risk of developing gastroparesis after gastric surgery. In addition, an attempt was made to pace the stomach with an electrical stimulus and determine the effect of pacing on early postoperative gastric emptying. Gastric dysrhythmias (bradygastria, slow wave frequency < 2 cycles/min; tachygastria, slow wave frequency > 4 cycles/min) persisted beyond the first postoperative day in 6 patients (35%). Delayed gastric emptying was identified by a radionuclide meal in 15 patients (88%), but symptoms of gastroparesis developed in only 6 of 15 (40%). Patients with postoperative gastroparesis had more frequent dysrhythmias than asymptomatic patients (67% vs. 18%), but these differences were not significant, although we cannot exclude a type II statistical error. Gastric rhythm was entrained in 10 of 16 patients (63%). Pacing increased the gastric slow wave frequency (3.1 vs. 4.1 cycles/min; P < 0.01) but did not improve gastric emptying (gastric retention at 60 minutes, 86% +/- 6% for control and 90% +/- 2% for paced). In conclusion, gastric dysrhythmias do not appear to play a major role in the development of postsurgical gastroparesis. Although gastric rhythm could be entrained in the majority of patients, pacing did not improve gastric emptying overall. PMID- 1451976 TI - Estradiol is trophic for colon cancer in mice: effect on ornithine decarboxylase and c-myc messenger RNA. AB - The mitogenic role of estradiol on the growth of colon cancer was examined in mice. Sham-operated or ovariectomized mice were injected with cancer cells and received estradiol treatment. Tumor growth was noted: tumor weights were higher in female than male mice. The growth of the tumors was least in ovariectomized mice and highest in estradiol-treated ovariectomized mice. Tumor messenger RNA (mRNA) levels for ornithine decarboxylase (ODC) and proto-oncogenes c-myc, c-fos, and H-ras were examined. Two transcripts (2.2 and 2.7 kilobase pairs) of ODC were observed. The steady-state mRNA levels for ODC paralleled the changes observed in the weight of the tumors in all groups of animals. Less dramatic changes were observed in c-myc mRNA levels. No significant differences were observed in the mRNA levels for H-ras and c-fos. It thus appears likely that an increase in the ODC mRNA levels and, to a lesser extent, an increase in c-myc mRNA levels may be some of the important mechanisms by which estradiol mediates its growth effects on colon cancer cells in vivo. PMID- 1451977 TI - Modulation of salivary secretion by acid infusion in the distal esophagus in humans. AB - To examine the relationship between esophageal acid exposure and development of salivation and heartburn, 15 healthy subjects underwent perfusion of the distal esophagus with varying concentrations of hydrochloric acid, different-osmolality saline solutions, and deionized water. In five study subjects, hydrochloric acid was infused in the body of the stomach only. During the study, timed samples of whole and parotid saliva were collected and analyzed for flow rate and bicarbonate concentration. Only hydrochloric acid concentrations of 20 mmol/L or greater (pH 1.8 or lower) induced a rapid (within 2 minutes) and significant (P < 0.05) increase in salivation. The hydrochloric acid-induced salivation was associated with significant (P < 0.05) increase in bicarbonate secretion in both parotid and whole saliva samples. Intravenous atropine administration completely inhibited hydrochloric acid-induced salivary secretion in all six subjects. Changes in osmolality of saline solution infused in the esophagus and hydrochloric acid infused in the stomach did not significantly alter parotid and whole saliva flow rates. These data suggest that in humans, rapid salivation in response to esophageal mucosal exposure to intraluminal hydrochloric acid is a pH dependent and osmolality-independent phenomenon that is most likely mediated by pH-sensitive chemoreceptors located in the esophageal mucosa. PMID- 1451978 TI - Decreased expression of transforming growth factor alpha during differentiation of human pancreatic cancer cells. AB - The relationship between cell differentiation and transforming growth factor alpha (TGF-alpha) expression in human pancreatic cancer cells was analyzed in Capan 1 cells. These cells differentiate either spontaneously or after butyrate treatment. During differentiation (spontaneous or butyrate induced), TGF-alpha messenger RNA (mRNA) levels decreased, whereas the TGF-beta 1 mRNA levels remained unchanged. TGF-alpha was present in cells as proTGF-alpha, which decreased after butyrate treatment. Secretion of TGF-alpha was not found. Under the two conditions of differentiation, the membrane-bound protein kinase C activity was also reduced. Conversely, long-term phorbol ester treatment increased both membrane-bound protein kinase C activity (260%) and TGF-alpha mRNA level (500%), a not significant increase of TGF-beta 1 mRNA was observed. However, phorbol 12-myristate-13-acetate did not induce TGF-alpha synthesis or secretion. These data suggest that expression of TGF-alpha can be reduced in cancer cells; they also suggest the existence of a relationship between TGF-alpha expression and cell differentiation. In addition, the protein kinase C-induced TGF-alpha mRNA level was not followed by the increase of TGF-alpha biosynthesis, suggesting a translational control. Finally, the expression of TGF-alpha and beta 1 messengers appears to be differently regulated. PMID- 1451979 TI - Immunoglobulin A antibody to a 200-kilodalton cytosolic acetaldehyde adduct in alcoholic hepatitis. AB - Considerable clinical and experimental evidence points to the importance of immune responses in the development of alcoholic liver disease. In the present study it was investigated whether circulating antibodies from patients with alcoholic liver disease recognize acetaldehyde-liver protein adducts. Cytosolic and microsomal fractions from livers of Wistar rats or from normal human liver were incubated with acetaldehyde (0.5-2.5 mmol/L) and/or cyanoborohydride (100 mmol/L) then analysed by immunoblotting. Cytosolic fractions that had been incubated with acetaldehyde and cyanoborohydride expressed a 200-kilodalton protein antigen not present in untreated fractions or fractions incubated with acetaldehyde or cyanoborohydride alone. The 200-kilodalton antigen was recognized by immunoglobulin (Ig)A antibodies in a large proportion of sera from patients with alcoholic hepatitis (70%, n = 23), but in significantly smaller proportions of sera from patients with alcoholic cirrhosis without hepatitis (30%, n = 10; P < 0.05), heavy drinkers without overt liver disease (20%, n = 10; P < 0.02), patients with nonalcoholic liver disease (35%, n = 17; P < 0.05), or normal control subjects consuming moderate quantities of alcohol (25%, n = 20%; P < 0.005). These results indicate that IgA antibodies to a 200-kilodalton acetaldehyde-protein adduct are present in a large proportion of patients with alcoholic liver disease and in a significantly smaller proportion of other individuals. PMID- 1451980 TI - Increased gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy. AB - To characterize gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy, 34 cirrhotics with this lesion and 24 noncirrhotics were studied by reflectance spectrophotometry and laser-Doppler flowmetry during endoscopy. A significant correlation was observed between the hemoglobin content of the gastric mucosa, measured by reflectance spectrophotometry, and the serum hemoglobin concentration both in cirrhotics (r = 0.72) and in noncirrhotics (r = 0.87). IHb ratio (hemoglobin content of gastric mucosa divided by blood hemoglobin concentration) was higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001), whereas the oxygen content of the gastric mucosa was similar in both groups. This pattern indicates that cirrhotics with portal hypertensive gastropathy have increased gastric perfusion without congestion. Gastric blood flow estimated by laser-Doppler was significantly higher in cirrhotics with portal hypertensive gastropathy than in noncirrhotics (P < 0.001). In cirrhotic patients, gastric areas with cherry red spots showed a significantly higher IHb ratio than areas with a mosaic or scarlatina pattern (P < 0.05). The magnitude of changes in gastric perfusion and the endoscopic severity of portal hypertensive gastropathy had no relationship with the degree of portal hypertension or the azygos blood flow. PMID- 1451981 TI - Cytological changes in the pancreas of transgenic mice overexpressing transforming growth factor alpha. AB - Transgenic mice overexpressing human transforming growth factor alpha (TGF-alpha) predictably develop an enlarged, firm pancreas. The present study investigated the changes that occur in the different components of the pancreas in these animals. The increase in size of the pancreas may be accounted for by increased connective tissue. The added collagen is mainly type I. Thin, elongate fibroblasts are frequently bordered by a basal lamina, a relationship that is normally restricted to the perineurium. Collagen is intimately associated with epithelial cells. Fingers of connective tissue extend close to acinar lumina. Redifferentiation of acinar cells produces tubular complexes. In some cases, acinar cells take on the appearance of ductular cells. In some, there is a transition to mucin-producing cells. Intermediate forms between acinar and mucin producing cells are present. The growth factor is localized in acinar cells and decreases with redifferentiation. The pancreas of these animals routinely displays characteristics that also are observed in diseases of the exocrine pancreas in humans, including fibrosis and redifferentiation. It is likely that the changes are the result of both direct and indirect effects of TGF-alpha, some of which may parallel altered control mechanisms in human pancreatic disease. Study of this model may provide clues to understanding the initiation of fibrosis and redifferentiation in human pancreas. PMID- 1451982 TI - Primary sclerosing cholangitis: refinement and validation of survival models. AB - The natural history of primary sclerosing cholangitis was studied in 426 patients from five medical centers. The median follow-up time was 3.0 years (range, 0.01 16.6 years); 100 patients had died by the time of last follow-up. Survival analysis (Cox proportional-hazards regression) was used to identify the variables most useful in predicting survival of patients with primary sclerosing cholangitis. Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying. A mathematical model to predict survival of patients with primary sclerosing cholangitis (based on referral values of those predictors) was statistically validated using two methods. Confidence intervals for predicting patient-specific survival probabilities are also presented. This model to predict survival could be used to stratify participants in therapeutic trials, counsel patients and their families, decide on candidacy for and timing of liver transplantation, and provide mathematical controls for evaluating the efficacy of therapies for primary sclerosing cholangitis, including transplantation. PMID- 1451983 TI - Human pancreatic tissue concentration of bactericidal antibiotics. AB - Pancreatic infection represents the most important cause of fatal outcome in human acute pancreatitis. In a comparative analysis, human pancreatic tissue concentrations of 10 different bactericidal antibiotics were determined in 89 patients undergoing pancreatic surgery. Concentrations of the antibiotics were determined in the blood and pancreatic tissue using high-pressure liquid chromatography. Pancreatic tissue concentrations 120 minutes after intravenous administration were as follows: mezlocillin, 19.0 mg/kg; piperacillin, 20.3 mg/kg; cefotaxime, 9.1 mg/kg; ceftizoxime, 7.9 mg/kg; netilmicin, 0.4 mg/kg; tobramycin, 0.4 mg/kg; ofloxacin, 1.7 mg/kg; ciprofloxacin, 0.9 mg/kg; imipenem, 6.0 mg/kg; metronidazole, 3.5 mg/kg. Three groups of antibiotics were established: group A, substances with low tissue concentrations (netilmicin, tobramycin), which were below the minimal inhibitory concentrations of most bacteria found in pancreatic infection; group B, antibiotics with pancreatic tissue concentrations which were sufficient to inhibit some but not all bacteria in pancreatic infection (mezlocillin, piperacillin, ceftizoxime, cefotaxime); group C, substances with high pancreatic tissue levels as well as high bactericidal activity against most of the germs present in pancreatic infection (ciprofloxacin, ofloxacin, imipenem). These data could serve as the basis for adequate antibiotic prophylaxis or treatment of pancreatic infection. PMID- 1451984 TI - Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition. AB - The effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) biosynthesis on the splanchnic and systemic circulation, were investigated in rats with cirrhosis induced by carbon tetrachloride. Portal hypertension in these rats was accompanied by decreased arterial blood pressure and peripheral vascular resistance as well as by splanchnic vasodilation with increased portal venous inflow and decreased splanchnic resistance. Intravenous bolus administration of L-NMMA (25 mg/kg) significantly increased systemic blood pressure and decreased cardiac output. L-NMMA also significantly increased systemic and splanchnic vascular resistance; whereas blood flow to the stomach, small intestine, colon, pancreas, mesentery, spleen, and kidney was decreased significantly. L-NMMA did not alter the portal pressure or portosystemic shunting in these cirrhotic rats, yet portal vascular resistance increased, suggesting effects on the intrahepatic and collateral circulation. Pretreatment with L arginine (300 mg/kg) prevented the hemodynamic changes induced by L-NMMA. These findings support the concept that local excess formation of NO contributes to changes in splanchnic circulation associated with portal hypertension in cirrhosis. PMID- 1451985 TI - Comparison of different treatment modalities in experimental pancreatitis in rats. AB - Lipolytic enzymes may play a role in the pathogenesis of acute pancreatitis. Therefore, the effects of a lipase inhibitor, THL (tetrahydrolipstatin), a protease inhibitor, FUT (nafamostat mesilate), and albumin under different conditions in rats were investigated. (a) Isolated pancreatic acini were incubated with pancreatic homogenates and triglycerides or lecithin with or without albumin and the degree of cellular destruction quantitated. (b) Taurocholate was injected into the pancreatic duct of isolated pancreas and the organ continuously perfused with either FUT, THL, or albumin. Organ damage was evaluated by measurement of pancreatic enzymes in the portal effluence. (c) Necrotizing pancreatitis was induced in vivo via retrograde taurocholate injection. FUT, THL, or albumin was applied either intravenously or injected into the pancreatic parenchyma. (a) Albumin prevented the cellular damage caused by both fatty acids and lysolecithin. (b) THL was ineffective, FUT lowered the release of pancreatic enzymes into the portal effluence, and albumin was most effective. (c) Albumin prevented the development of panlobular necrosis and lowered the degree of extrapancreatic fat necrosis. Albumin, via its ability to bind detergents, may have therapeutic implications. PMID- 1451986 TI - Possible role of transforming growth factor alpha in the pathogenesis of Menetrier's disease: supportive evidence form humans and transgenic mice. AB - Menetrier's disease is an uncommon disorder of unknown etiology characterized by enlarged gastric folds with foveolar hyperplasia and cystic dilatation of gastric glands. Biochemical features that are seen frequently include hypoproteinemia, hypochlorhydria, and increased gastric mucus. Because transforming growth factor alpha (TGF alpha) is an epithelial cell mitogen that inhibits gastric acid secretion and increases gastric mucin content, we hypothesized that its altered expression might be involved in the pathogenesis of this disease. Therefore, we characterized TGF alpha immunoreactivity in the gastric mucosa of 4 patients with Menetrier's disease. In contrast to the normal pattern of TGF alpha immunostaining in which TGF alpha appears most concentrated in parietal cells, there was intense staining in the majority of mucous cells in the gastric mucosa of patients with Menetrier's disease. In one patient from whom sufficient fresh tissue was obtained to isolate RNA, expression of TGF alpha and the epidermal growth factor receptor was higher in the gastric mucosa relative to a normal control. In addition, metallothionein-TGF alpha transgenic mice, which overexpress TGF alpha in gastric mucosa, show a number of features characteristic of Menetrier's disease. These include foveolar hyperplasia and glandular cystic dilatation, increased gastric neutral mucin staining, and reduced basal and histamine-stimulated rates of acid production. Taken together, observations derived from the human material and correlation with data from a transgenic mouse model support an important role for TGF alpha in the pathogenesis of Menetrier's disease. PMID- 1451987 TI - Pacing the gut. PMID- 1451988 TI - Immune responses to acetaldehyde-protein adducts: role in alcoholic liver disease. PMID- 1451989 TI - Prenylation of the large hepatitis delta virus antigen: a target for antiviral therapy. PMID- 1451990 TI - Bleeding esophageal varices--inject or band? PMID- 1451991 TI - The special problem of colitis in the elderly: expanding the spectrum. PMID- 1451992 TI - Acalculous right upper quadrant pain: is cholescintigraphy worthwhile? PMID- 1451993 TI - Determinants of portal hypertensive gastropathy reconsidered. PMID- 1451994 TI - Hemodynamics of octreotide in hepatitis B-related cirrhosis. PMID- 1451995 TI - Manometry in classic and vigorous achalasia. PMID- 1451996 TI - Selective bowel decontamination and liver regeneration. PMID- 1451997 TI - Malabsorption secondary to intestinal hurry. PMID- 1451998 TI - Does erythromycin really have a prokinetic effect on the gallbladder? PMID- 1451999 TI - Atrial natriuretic factor in experimental cirrhosis. PMID- 1452000 TI - [Hormonal contraception and substitution therapy: the importance of progestogen for cardiovascular diseases]. AB - Epidemiological data have demonstrated, that the progestogen component of oral contraceptives is involved in the development of hypertension, ischaemic heart diseases and stroke. It had been suggested, that atherosclerotic lesions due to the unfavourable effect on lipid metabolism of progestogens with androgenic properties, play a causal role. It has, however, been shown, that there is no development of atherosclerosis despite reduced HDL and elevated LDL, presumably because of the induction of hepatic LDL- and remnant-receptors by the strong effect of ethinyl-oestradiol upon the liver. A series of experimental and clinical findings indicates that vasospasms caused by the vasoconstrictory effect of progestogens are involved in the development of arterial thromboses. In postmenopausal women, the additional administration of progestogens to the oestrogen treatment may trigger ischaemic diseases, particularly in the presence of vascular lesions. Oestrogens exercise a pronounced vasodilatory effect and stabilize the vascular tonus--through changes in the responsiveness of endothelium and smooth muscle cells to vasoactive compounds, through modulation of neurotransmitter release from nerve endings, and through direct blocking of calcium channels. The effects depend essentially on an intact endothelium. By a direct action on the vascular wall, progestogens increase the sensitivity of arteries to vasoconstrictory compounds and reduce blood flow. As aldosterone increases the number of beta-adrenergic receptors in the arterial smooth muscle cells and thus act vasodilatorily, it cannot be excluded, that progestogens with high affinity to the aldosterone receptor and antimineralocorticoid properties, may exert a strong vasoconstrictory effect.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1452001 TI - [Diagnosis of tubal function using intraluminal ultrasound--initial results]. AB - The extremely small ultrasound transducers of the intraluminal ultrasound instruments, introduced via catheters, enable diagnosis to be made inside hollow organs. In order to test the possible uses and indications for this new method in gynaecology, we conducted preliminary examinations in the diagnosis of the uterus and tubes. We employed an intraluminal instrument supplied by Dornier. The intraluminal transducers of this instrument have a diameter of 3.5 and 5 F. Following in-vitro examinations, hysteroscopy and laparoscopy/laparotomy were performed in 15 patients during which the transducer was pushed up via the cervix uteri to the tubes with full vision. This was successful in all 15 patients; in 9 cases the transducer could be pushed as far as the distal end. The tubal walls were examined in detail by this method and for the first time it became possible to achieve functional diagnosis of the motility of the tubes. Strictures can be visualised. The endometrium of the uterus, however, cannot as yet be diagnosed exactly by the present-day state of examination technique. If image quality can be further improved, this method will be the first to enable a functional diagnosis of the tubes and the uterus. PMID- 1452002 TI - [Fetal plexus cysts. An indication for prenatal karyotyping]. AB - From March 1988 to September 1990, 1844 patients (pregnant women) were sonographically examined following a pregnancy monitoring programme and for further diagnostic clarification of unclear sonographic patterns. The ultrasound examinations were carried out with a 3.5 Mhz convex transducer, and by pregnancies before the 16th week with a 5 Mhz vaginal transducer (Toshiba SSA 250 a), respectively. In 13 cases (0.7%), foetal chorioidal plexus cysts were found; in 6 of them they occurred unilaterally and in the other 7 bilaterally. In general, most of the cases were diagnosed between the 13th and 22nd weeks of pregnancy. All unilateral cysts appeared transitorily, were of small size and receded by the 24th week of pregnancy. From the 7 patients with bilateral plexus cysts, 4 foetuses showed no signs of anatomical abnormalities. In the other 3 foetuses, it was possible, to recognise further anatomical abnormalities, when performing ultrasound i.e. 2 of them proved to be a trisomy 18 and the third case a trisomy 21. PMID- 1452003 TI - [Pelviscopic hysterectomy--a prospective comparative study of 40 cases]. AB - We review to date 20 pelviscopic extirpations of the uterus. This new method of hysterectomy shows some advantages over the common vaginal hysterectomy. Anatomy of the supporting ligaments of the uterus remains the same, recovery from the operation goes quicker. Morbidity rate seems to be less than in the case of vaginal hysterectomy. PMID- 1452004 TI - [Systematic aspects of depot peritoneal lavage in gynecology]. AB - After 9 years of experience in gynaecology, the systematics of depot peritoneal lavage is now open for discussion. Intraoperatively, a liquid residual depot of 1.5-2.0 l Ringer's solution remains, while the abdominal cavity is continuously rinsed with varying amounts of liquid according to the indication. By maintaining the depot in all lavages, the formation of adhesions is therefore prevented. Forms and indications of the lavages: 1. "Postoperative Clear Lavage": a) Removal of blood and tissue residues must be removed b) Control/early diagnosis of secondary haemorrhage 2. "Adhesion Lavage": Prophylaxis 3. "Anti-septic Massive Lavage": In all cases of inflammatory diseases of the abdominal cavity, to prevent abscess and adhesion formation, and in peritonitis, to remove bacteria, endotoxins and detritus. In severe ascending infections, complete organ preservation was possible in 94% of 330 patients by combining early laparoscopy with an antiseptic massive lavage. Results of the first two indications will be published shortly. PMID- 1452005 TI - [The magnesium and calcium content of pre- and postmenopausal myometrium]. AB - Magnesium and calcium, as well as sodium and potassium, have an important influence on the physiology of contraction of the uterus. The ionic concentrations in the pre- and postmenopausal myometrium were examined. We assumed, that there are differences in the electrolytic contents because of the different functions of the corpus, isthmic part and cervix uteri during pregnancy and throughout labour. Small tissue samples from 37 premenopausal and 20 postmenopausal patients, who underwent an operation with different indications, were dissected after hysterectomy. Magnesium and calcium levels were determined by atomic absorption spectrophotometry and potassium and sodium by emission spectrometry in the wet tissue. In both groups, we found significant differences of the electrolytic contents of the myometrium. In the premenopausal uteri, the magnesium levels decrease significantly (p < 0.001) from the corpus (mean = 4.14 mmol/kg) to the cervix (mean = 2.14 mmol/kg). The same scenario can be observed for the potassium levels (Corpus mean = 56.2 mmol/kg and cervix mean = 25.4 mmol/kg). In contrary, the calcium levels (Corpus mean = 1.60 mmol/kg and cervix mean = 2.26 mmol/kg) and sodium levels (Corpus mean = 69.3 mmol/kg and cervix mean = 93.0 mmol/kg) increase significantly (p < 0.001). In the postmenopausal group, we found slightly elevated concentrations of magnesium, sodium and potassium. Only the calcium content of the corpus uteri rises up to three times about 20 years after the menopause (from mean = 1.60 mmol/kg) (p < 0.001). The electrolytic contents in the myometrium were shown to be different in the corpus, isthmus and cervix uteri.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452006 TI - [Subjective stress of adjuvant chemotherapy in breast cancer patients]. AB - 50 patients, suffering from carcinoma of the breast pT1-3 with concomitant metastatic affection of the lymph nodes with no evidence of distant metastases, and who received adjuvant chemotherapy (either CMF od AC/EC) were examined. Somatic and psychic interferences, the feeling of well-being and general condition, as well as a critical estimation of the clinical situation were assessed. Besides nausea and vomiting, and still prior to hair fall out, chemotherapy activated the memory of the carcinoma. 92% of the patients agreeing to chemotherapy described their decision as having been based exclusively on the medical information. Nevertheless, 30% feel insufficiently informed, so the fear of side effects, the waiting period prior to application, and the confrontation with the seriously ill, were described as a negative experience. An optimistic view with respect to improving the prognosis of the disease were correlated with chemotherapy: 74% would agree to a further chemotherapy. Psychic abnormalities, e.g. depressions, could not be shown following chemotherapy when compared to a reference population. PMID- 1452007 TI - [Acute non-immunologic hydrops fetalis with bilateral chylothorax in the 36th week of pregnancy]. AB - Since the introduction of anti-D gamma-globulin prophylaxis non-immune hydrops fetalis (NIHF) has become the relevant and more common form of fetal hydrops. A case of an NIHF with chylothorax, diagnosed in the 36th week of pregnancy, is discussed with regard to obstetrical and neonatological management. PMID- 1452008 TI - [Intraplacental hematoma following chorionic villi biopsy]. AB - One of the most typical complications following chorionic villae sampling (CVS) is vaginal bleeding shortly or some days after the intervention, resulting in abortion in some cases. We report on a case of intraplacental haematoma (pathology: massive subtotal acute haemorrhagic placental infarct), followed by acute placental insufficiency in the 29th week of pregnancy. Therefore, we decided on an emergency caesarean section. PMID- 1452009 TI - [The timing of patient education in surgical interventions]. PMID- 1452010 TI - [Society of Obstetrics and Gynecology in Berlin. Meeting of 8 January 1991]. PMID- 1452011 TI - [In the light of a petroleum lamp the operation could begin. Richard Frommel (1854-1912): pioneer in treatment of ruptured extrauterine pregnancy]. AB - Richard Frommel (1854-1912) can be called an outstanding German gynaecologist during the late 19th century. This article is intended to give a picture of his life, work, and personality. Frommel was director of the department of obstetrics and gynaecology at the university of Erlangen from 1887 to 1901. Science owes to him, amongst other contributions, an important impulse for changing the therapy of ruptured ectopic pregnancy. Up to the present day Frommel's name together with that of Johann Chiari (1817-1854), serve as eponyms for a special form of the amenorrhoea-galactorrhoea syndrome, namely, the persistent one-post partum. It remains puzzling why Frommel resigned office, when he was just 46 years old, giving up gynaecology completely only a short time later. PMID- 1452012 TI - Fine structure mapping and complementation studies of the metD methionine transport system in Salmonella typhimurium. AB - A fine structure deletion map of the metD region of the chromosome of Salmonella typhimurium responsible for a high-affinity methionine transport system has been constructed. Complementation tests involving the introduction of metD+DNA contained in a pUC8 vector into metD strains indicated the presence of four complementation groups in the metD region. This suggested that the methionine system belongs to the osmotic shock-sensitive class of transport system, and therefore should possess a periplasmic methionine-binding protein and several membrane proteins. But a deletion mutation covering all known metD point mutations did not affect the level of a methionine binding activity in osmotic shock fluids, suggesting either that the deletion did not extend into the gene encoding the binding protein, or that the binding activity is not associated with the metD system. Possible reasons for the failure to isolate mutations in the gene for the binding protein are discussed. PMID- 1452013 TI - Genetics of sexual isolation in females of the Drosophila simulans species complex. AB - Genetic analysis of hybrids between Drosophila simulans and D. sechellia shows that sexual isolation in females is caused by at least two genes, one on each major autosome, while the X chromosome has no effect. These results are similar to those of a previous study of hybrids between D. simulans and another sibling species, D. mauritiana. In this latter hybridization, each arm of the second chromosome carries genes causing sexual isolation in females, implying a total divergence of at least three loci. The genetic similarity between the D. simulans/D. mauritiana and D. simulans/D. sechellia hybridizations probably results from independent evolution and not phylogenetic artifacts, because the dominance relationships and behavioural interactions differ between the two hybridizations. The lack of an X-chromosome effect on sexual isolation contrasts with genetic studies of post-zygotic reproductive isolation, which invariably show strong effects of this chromosome. PMID- 1452014 TI - Polymorphisms distinguishing different mouse species and t haplotypes. AB - Three anonymous chromosome 17 DNA markers, D17Tu36, D17Tu43, and D17Le66B, differentiate between house mouse species and/or between t chromosomes. The D17Tu36 probe, which maps near the Fu locus and to the In(17)4 on t chromosomes, identifies at least 15 haplotypes, each haplotype characterized by a particular combination of DNA fragments obtained after digestion with the Taq I restriction endonuclease. Ten of these haplotypes occur in Mus domesticus, while the remaining five occur in M. musculus. In each of these two species, one haplotype is borne by t chromosomes while the other haplotypes are present on non-t chromosomes. The D17Tu43 probe, which maps near the D17Leh122 locus and to the In(17)3 on t chromosomes, also identifies at least 15 haplotypes in Taq I DNA digests, of which nine occur in M. domesticus and six in M. musculus. One of the nine M. domesticus haplotypes is borne by t chromosomes, the other haplotypes are borne by non-t chromosomes; two of the six M. musculus haplotypes are borne by t chromosomes and the remaining four by non-t chromosomes. Some of the D17Tu43 haplotypes are widely distributed in a given species, while others appear to be population-specific. Exceptions to species-specificity are found only in a few mice captured near the M. domesticus-M. musculus hybrid zone or in t chromosomes that appear to be of hybrid origin. The D17Leh66B probe, which maps to the In(17)2, distinguishes three haplotypes of M. domesticus-derived t chromosomes and one haplotype of M. musculus-derived t chromosomes. Because of these characteristics, the three markers are well suited for the study of mouse population genetics in general and of t chromosome population genetics in particular. A preliminary survey of wild M. domesticus and M. musculus populations has not uncovered any evidence of widespread introgression of genes from one species to the other; possible minor introgressions were found only in the vicinity of the hybrid zone. Typing of inbred strains has revealed the contribution of only M. domesticus DNA to the chromosome 17 of the laboratory mouse. PMID- 1452015 TI - The role of DNA replication and isochores in generating mutation and silent substitution rate variance in mammals. AB - It has been suggested that isochores are maintained by mutation biases, and that this leads to variation in the rate of mutation across the genome. A model of DNA replication is presented in which the probabilities of misincorporation and proofreading are affected by the composition and concentration of the free nucleotide pools. The relationship between sequence G+C content and the mutation rate is investigated. It is found that there is very little variation in the mutation rate between sequences of different G+C contents if the total concentration of the free nucleotides remains constant. However, variation in the mutation rate can be arbitrarily large if some mismatches are proofread and the total concentration of free nucleotides varies. Hence the model suggests that the maintenance of isochores by the replication of DNA in free nucleotide pools of biased composition does not lead per se to mutation rate variance. However, it is possible that changes in composition could be accompanied by changes in concentration, thus generating mutation rate variance. Furthermore, there is the possibility that germ-line selection could lead to alterations in the overall free nucleotide concentration through the cell cycle. These findings are discussed with reference to the variance in mammalian silent substitution rates. PMID- 1452016 TI - Evidence for random distribution of sequence variants in Tenebrio molitor satellite DNA. AB - Tenebrio molitor satellite DNA has been analysed in order to study sequential organization of tandemly repeated monomers, i.e. to see whether different monomer variants are distributed randomly over the whole satellite, or clustered locally. Analysed sequence variants are products of single base substitutions in a consensus satellite sequence, producing additional restriction sites. The ladder of satellite multimers obtained after digestion with restriction enzymes was compared with theoretical calculations and revealed the distribution pattern of particular monomer variants within the satellite. A defined higher order repeating structure, indicating the existence of satellite subfamilies, could not be observed. Our results show that some sequence variants are very abundant, being present in nearly 50% of the monomers, while others are very rare (0-1% of monomers). However, the distribution of either very frequent, or very rare sequence variants in T. molitor satellite DNA is always random. Monomer variants are randomly distributed in the total satellite DNA and thus spread across all chromosomes, indicating a relatively high rate of sequence homogenization among different chromosomes. Such a distribution of monomer variants represents a transient stage in the process of sequence homogenization, indicating the high rate of spreading in comparison with the rate of sequence variant amplification. PMID- 1452017 TI - Involvement of the Escherichia coli RNA polymerase alpha subunit in transcriptional activation by the bacteriophage lambda CI and CII proteins. AB - Escherichia coli cells harbouring the rpoA341 mutation produce an RNA polymerase which transcribes inefficiently certain operons subject to positive control. Here, we demonstrate that the rpoA341 allele also prevents lysogenization of the host strain by bacteriophage lambda, a process dependent upon the action of two phage-encoded activators. This phenomenon was shown to arise from an inability to establish an integrated prophage rather than a failure to maintain the lysogenic state. The inability of the rpoA341 host to support lysogenization could be completely reversed by CII-independent expression of int and cI in trans. These results led us to propose that the inhibition of lysogenization arises from a defective interaction between the phage lambda transcriptional activator CII and the mutant RNA polymerase at the phage promoters pI and pE. Finally, we also provide genetic evidence for impaired transcription of the cI gene from the CI activated promoter, pM in the rpoA341 background. PMID- 1452018 TI - Multiple protein tyrosine phosphatase-encoding genes in the yeast Saccharomyces cerevisiae. AB - In higher eukaryotic organisms, the regulation of tyrosine phosphorylation is known to play a major role in the control of cell division. Recently, a wide variety of protein tyrosine phosphatase (PTPase)-encoding genes (PTPs) have been identified to accompany the many tyrosine kinases previously studied. However, in the yeasts, where the cell cycle has been most extensively studied, identification of the genes involved in the direct regulation of tyrosine phosphorylation has been difficult. We have identified a pair of genes in the yeast Saccharomyces cerevisiae, which we call PTP1 and PTP2, whose products are highly homologous to PTPases identified in other systems. Both genes are poorly expressed, and contain sequence elements consistent with low-abundance proteins. We have carried out an extensive genetic analysis of PTP1 and PTP2, and found that they are not essential either singly or in combination. Neither deletion nor overexpression results in any strong phenotypes in a number of assays. Deletions also do not affect the mitotic blockage caused by deletion of the MIH1 gene (encoding a positive regulator of mitosis) and induction of the heterologous Schizosaccharomyces pombe wee1+ gene (encoding a negative regulator of mitosis). Molecular analysis has shown that PTP1 and PTP2 are quite different structurally and are not especially well conserved at the amino acid sequence level. Low stringency Southern blots indicate that yeast may contain a family of PTPase encoding genes. These results suggest that yeast may contain other PTPase encoding genes that overlap functionally with PTP1 and PTP2. PMID- 1452019 TI - Imported sequences in the mitochondrial yeast genome identified by nucleotide linguistics. AB - In addition to universally appearing mitochondrial (mt) genes, origins of replication and transcription start regions typical of all mt genome variants of the yeast Saccharomyces cerevisiae, the mt genomes of some of the strains contain variable sequences. These sequences are apparently largely dispensable. They are mainly composed of group-I and -II introns and intergenic open reading frames (ORFs). Many of the introns contain ORFs, some of which were shown by genetic and biochemical means to be involved in splicing and transposition of the mt introns. Some of the optional sequences are hypothesized to be mobile genetic elements. Nucleotide (nt) sequences of the mt genome of S. cerevisiae were examined by analyzing occurrences of oligodeoxyribonucleotide (oligo) 'words'. This linguistic technique had been found to be sensitive to both function and origin of the sequence [Pietrokovski et al., J. Biomol. Struct. Dyn. 7 (1990) 1251 1268]. A clear difference is found between the oligo vocabularies of the optional and basic yeast mt sequences. The difference is mainly located in protein coding segments of the optional sequences which contain conserved amino acid motifs, characteristic of intronic and intergenic ORFs. The use of nt linguistics to detect the sequence dissimilarity and its causes in yeast mitochondria provides fast and straightforward results, identifying the intronic and intergenic ORFs as DNA sequences of foreign, non-mt origin. PMID- 1452020 TI - High-level production of a peroxisomal enzyme: Aspergillus flavus uricase accumulates intracellularly and is active in Saccharomyces cerevisiae. AB - Strains of Saccharomyces cerevisiae producing Aspergillus flavus uricase (Uox) have been constructed. An artificial promoter which combined the upstream and downstream sequences of the GAL7 and ADH2 promoters, respectively, was found to be efficient in directing the synthesis of uaZ mRNAs encoding Uox. A good proportionality between the copy number of the uaZ expression cassette and the level of Uox production was found in the range of 1-10 copies. Transformants accumulated active and soluble Uox to a level exceeding 13% of total protein, as deduced from enzymatic assays. This relative level could be improved two- to threefold by using a recipient strain in which the wild-type GAL4 gene had been deleted and which expressed a GAL4 construct placed under the control of the ADH2 promoter. PMID- 1452021 TI - Structural and functional analysis of the amdR regulatory gene of Aspergillus oryzae. AB - We have isolated the Aspergillus oryzae homologue of the amdR regulatory gene of Aspergillus nidulans by cross hybridization. Sequence analysis and functional studies have shown that the amdR genes are highly conserved and functionally interchangeable between the two species. The homology between the two genes extends throughout most of the coding sequences, including sequences encoding the DNA-binding domain and putative activation domains. Two regions of nonconserved sequence were also identified. Studies using various amdS::lacZ fusion constructs indicate that the A. oryzae gene product binds similar sequences and responds to inducer in a similar manner to the A. nidulans protein. Inactivation of the A. oryzae gene results in the inability to grow on gamma-amino-butyric acid (GABA) as a carbon and/or nitrogen source indicating that GABA utilization is amdR dependent in A. oryzae as it is in A. nidulans. PMID- 1452022 TI - Heterologous gene expression in Aspergillus niger: a glucoamylase-porcine pancreatic prophospholipase A2 fusion protein is secreted and processed to yield mature enzyme. AB - The cDNA gene encoding porcine pancreatic prophospholipase A2 (proPLA2) was cloned into an Aspergillus niger expression vector downstream of the glucoamylase (glaA) gene promoter region. When this construct was transformed into A. niger, no detectable PLA2 was produced. Evidence was obtained showing that the PLA2 gene was transcribed and that PLA2 is extremely susceptible to both intracellular and extracellular proteases of A. niger, thus indicating that translation products would be rapidly degraded. By fusing the proPLA2-encoding sequence to the entire glaA gene, secreted yields of PLA2 up to 10 micrograms/ml were obtained from a transformed protease-deficient strain of A. niger. PLA2 was secreted in young cultures as a fusion protein, but in older cultures, it was processed from the glucoamylase carrier protein. Secreted PLA2 was shown to be enzymatically active and to have the correct N-terminal amino acid (aa) sequence, although another form of processed PLA2 was also produced. This form included two aa of the proregion from PLA2. The potential for improving yields of secreted heterologous proteins from A. niger still further is discussed. PMID- 1452023 TI - Cloning and differential expression during the sexual cycle of a meiotic endonuclease-encoding gene from the basidiomycete Coprinus cinereus. AB - The naturally synchronous meiosis of the fungus, Coprinus cinereus, provides an ideal system for the investigation of differential gene expression in relation to meiosis and fruiting body development. We have cloned a cDNA from the fruiting body of C. cinereus encoding the 12-kDa subunit of a meiotic endonuclease (mENase). The identification of the 12-kDa subunit cDNA clone was achieved by the mENase antiserum against a lambda gt11 cDNA expression library. It was confirmed by a direct match of the amino acid (aa) sequence obtained from purified 12-kDa polypeptide with the nucleotide sequence. Northern blot analysis using the cDNA clone as a probe showed that the mENase-encoding gene (MenA) for the 12-kDa subunit was expressed mainly in fruiting bodies and at a very low level in the asexual vegetative mycelium. In addition, it was differentially expressed in the early meiotic stages. The MenA transcript was most abundant in fruiting body primordia prior to the premeiotic S-phase; it remained high from karyogamy to early pachytene, declined drastically by late pachytene and diplotene, and was undetectable by sterigma stage. Western blot analysis showed that the mENase protein was produced at a very low level in mycelium; it was produced in great quantity during the early meiotic stages and decreased to a low level at the end of meiosis. PMID- 1452024 TI - Mutagenesis and regulation of the cysJ promoter of Escherichia coli K-12. AB - The cysJ promoter of Escherichia coli K-12, which is positively controlled by the CysB regulatory protein, was localized through the formation of a fusion of cysJ, the gene encoding NADPH-cytochrome c reductase with lacZ. The position of the transcription start point was determined and the orientation of transcription was shown to be counterclockwise on the E. coli K-12 map. Oligodeoxyribonucleotide directed mutagenesis of the inferred -10 and -35 regions indicated that both sites could be altered to produce promoter 'down' mutations. When the -10 region was made to agree with the -10 consensus sequence, there was increased function under conditions of repression (that is, in the presence of cysteine). Upstream deletions, as well as mutations in a region proposed to be involved in binding of the CysB regulatory protein, identified sequences important for promoter activity from -90 to -78 and from -71 to -66. By comparison of the sequences of four cys promoters, a possible CysB-binding site was found which included the region shown to be required for the positive regulation of the cysJ promoter. PMID- 1452025 TI - A small plasmid for recombination-based screening. AB - We reported recently the construction of the 4.4-kb R6K-derived pMAD1 plasmid carrying supF [Stewart et al., Gene 106 (1991) 97-101] that does not share nt sequences with ColE1 and therefore permits recombination-based screening of lambda libraries that contain ColE1 sequences. Here we describe the construction of the 2.5-kb R6K-derived plasmid, pMAD3, that lacks the pi-encoding pir gene required for R6K replication. To supply pi [Inuzuka and Helinski, Proc. Natl. Acad. Sci. USA 75 (1978) 5381-5385] in trans, we employed pPR1 delta 22pir116, referred to henceforth as pPR1 [McEachern et al., Proc. Natl. Acad. Sci. USA 86 (1989) 7942-7946; Dellis and Filutowicz, J. Bacteriol. 173 (1991) 1279-1286]. Plasmid pMAD3 is small enough to be amplified readily by PCR [Saiki et al., Science 230 (1985) 1350-1354]. This permits the insertion of larger fragments and the retrieval of larger lambda inserts, as well as the use of a simplified PCR based cloning protocol which utilizes annealing rather than ligation to create recombinants in pMAD3 [Nisson et al., PCR Methods and Applications 1 (1991) 120 123]. PMID- 1452026 TI - Cloning and expression in Escherichia coli of the gene encoding an extracellular deoxyribonuclease (DNase) from Aeromonas hydrophila. AB - The gene encoding an extracellular DNase from Aeromonas hydrophila CHC-1 has been cloned and sequenced. Following expression of the dns in Escherichia coli, it was revealed that some of the cloned enzyme was present in the cell-free extracellular supernatant fluid, and there was no cell lysis and concurrent release of cytoplasmic or periplasmic proteins. Therefore, results suggest that E. coli cells were capable of secreting the DNase extracellularly, albeit very inefficiently. The dns is transcribed from its own promoter in E. coli, and expressed as a 25-kDa product, as determined by sodium dodecyl sulfate polyacrylamide-gel electrophoresis of the culture supernatant preparations followed by a DNA-hydrolysis assay. Nucleotide sequence analysis predicted a single open reading frame of 690 bp encoding a 230-amino acid (aa) polypeptide, with a potential 20-aa signal peptide located at the N terminus of the predicted protein. The deduced aa sequence of the entire protein is highly homologous with that of the DNase of Vibrio cholerae. PMID- 1452027 TI - Cloning of a gene from Bacillus cereus with homology to the mreB gene from Escherichia coli. AB - We have cloned and sequenced a gene coding for a putative shape-determining protein (MreB) highly homologous to the mreB gene product of Escherichia coli. The amino acid (aa) identity was 53% and the similarity 72%. The gene is expressed early in the logarithmic phase. The aa sequence comparison showed that the protein, like the E. coli MreB, has structural similarity to actin and heat shock protein Hsc70 encoded by a new super-gene family. PMID- 1452028 TI - A series of shuttle vectors for Bacillus subtilis and Escherichia coli. AB - A series of shuttle vectors for Bacillus subtilis and Escherichia coli was developed. These are derived from one basic construct composed of parts of the Gram+ plasmid pUB110 and the Gram- plasmid pBR322. They contain multiple cloning sites flanked by transcriptional terminators. In one plasmid, a vegetative B. subtilis promoter drives transcription of inserted genes. For the construction of operon and gene fusions, the cat of pUB112 and the lacZ gene of E. coli were employed as reporter genes. With these vectors, cloning and expression of genes as well as probing of regulatory signals can be performed in B. subtilis and E. coli. PMID- 1452029 TI - Cloning and sequence analysis of the gene encoding L-lactate dehydrogenase from Lactococcus lactis: evolutionary relationships between 21 different LDH enzymes. AB - Lactate dehydrogenase (LDH; EC1.1.1.27) is a key enzyme in the fermentation of milk by lactic acid bacteria used in the dairy industry. An 800-bp DNA fragment containing part of the gene (ldh) encoding LDH was amplified from Lactococcus lactis in a polymerase chain reaction using primers designed from the partial amino acid sequence of a lactococcal LDH. This fragment was radioactively labelled and used to probe a phage lambda library of Lc. lactis genomic DNA. Fragments containing ldh were subcloned from lambda to pUC13 and pUC18 and a 1.2 kb region was sequenced. The deduced aa sequence reveals that the lactococcal LDH is highly homologous to the LDHs of other organisms. The active site and several other domains of unknown function are highly conserved between all LDH enzymes (prokaryotic and eukaryotic). An evolutionary study of LDH sequences clearly divides the prokaryotic from the eukaryotic enzymes except for the Bifidobacterium longum LDH which anomalously groups with the eukaryotic enzymes. The LDHs from Gram-positive bacteria form a separate group from the enzymes from the Gram-negative organisms. The lactococcal LDH is phylogenetically closest to the streptococcal LDH. PMID- 1452030 TI - Sequence of a Rhodococcus gene encoding a protein with extensive homology to the mammalian propionyl-CoA carboxylase beta chain. AB - Sequence analysis of a 2-kilobase DNA fragment from Rhodococcus sp. NI86/21 revealed an open reading frame encoding a 476-amino-acid protein with striking homology to the rat and human propionyl-CoA carboxylase beta subunits. The nucleotide sequence of a corresponding prokaryotic gene has not yet been reported. Upstream, the C-terminal part of a putative beta-ketoacyl synthase was identified. PMID- 1452031 TI - A homolog of the proteasome-related RING10 gene is essential for yeast cell growth. AB - Proteasomes are intracellular protein complexes displaying multiproteolytic activities. These complexes have been implicated in the antigen degradation process that generates peptides associated with the major histocompatibility complex (MHC) class-I molecule. RING10 and RING12 are genes encoded by the class II region of the human MHC that have sequence homology to proteasome-encoding genes. We have identified a yeast gene, called PRG1, that encodes a protein predicted to contain 55.6% sequence identity to 80% of the RING10 gene product. Genomic disruption of PRG1 revealed that it is essential for yeast cell growth. These data strongly indicate that the antigen-processing system present in vertebrates evolved from a basic cellular process present in all organisms. PMID- 1452033 TI - An inducible expression system for the production of human lactoferrin in Aspergillus nidulans. AB - The production and secretion of human lactoferrin (hLF) in Aspergillus nidulans is described. The hLF cDNA was expressed under the control of the strong ethanol inducible alcohol dehydrogenase (alcA) promoter. Recombinant hLF (re-hLF) is produced at levels up to 5 micrograms/ml. Approximately 30% of the re-hLF produced in this system is secreted into the growth medium. The re-hLF is indistinguishable from native hLF with respect to size and immunoreactivity. Furthermore, re-hLF is functional by the criterion of iron-binding capacity. The A. nidulans expression system offers an inexpensive, convenient method for the controlled production of mg amounts of biologically active mammalian glycoproteins. PMID- 1452032 TI - Cloning the Cryptococcus neoformans TRP1 gene by complementation in Saccharomyces cerevisiae. AB - We have cloned the phosphoribosyl anthranilate isomerase (PRAI)-encoding gene (TRP1) of Cryptococcus neoformans by genetic complementation in Saccharomyces cerevisiae. Sequence analysis of this gene revealed it to be 939 bp in length, and without known promoter or termination sequences. Unlike some of the filamentous fungi, where PRAI enzymatic activity is controlled by a trifunctional gene product, the C. neoformans PRAI appears to be unifunctional. PRAI of C. neoformans exhibits 39% amino acid (aa) sequence identity compared to the S. cerevisiae counterpart. The TRP1 gene of C. neoformans maps to different size chromosomes in strains with different serotypes. The cloning of this gene for vector constructions, and the demonstration that S. cerevisiae can be used as a surrogate for C. neoformans gene expression, should help with the molecular studies of this significant fungal pathogen in our increasing immunocompromised population. PMID- 1452034 TI - Cloning and molecular characterization of the glyceraldehyde-3-phosphate dehydrogenase-encoding gene and cDNA from the plant pathogenic fungus Glomerella cingulata. AB - The glyceraldehyde-3-phosphate dehydrogenase gene (gpdA) has been identified from a genomic DNA library prepared from the plant pathogenic fungus Glomerella cingulata. Nucleotide sequence data revealed that this gene codes for a putative 338-amino-acid protein encoded by two exons of 129 and 885 bp, separated by an intron 216 bp long. The 5' leader sequence is also spliced by an intron of 156 bp. A cDNA clone was prepared using the polymerase chain reaction, the sequence of which was used to confirm the presence of the intron in the coding sequence and the splicing of the 5' leader sequence. The transcriptional start point (tsp) was mapped at -253 nt from the site of the initiation of translation by primer extension and is adjacent to a 42-bp pyrimidine-rich region. The general structure of the 5' flanking region shows similarities to gpdA from Aspergillus nidulans. The putative protein product is 71-86% identical at the aa level to GPDs from Aspergillus nidulans, Cryphonectria parasitica, Curvularia lunata, Podospora anserina and Ustilago maydis. PMID- 1452035 TI - Sequence of the URA1 gene encoding dihydroorotate dehydrogenase from the basidiomycete fungus Agrocybe aegerita. AB - The URA1 gene encoding dihydroorotate dehydrogenase (DHOdehase) from the edible basidiomycete, Agrocybe aegerita, has been cloned by complementation of the Escherichia coli pyrD mutation. The nucleotide sequence of a 1531-bp genomic fragment carrying URA1 revealed two uninterrupted open reading frames (ORFs) separated by 61 bp. The larger ORF can encode a 328-amino acid (aa) DHOdehase that has 53% homology with the corresponding protein from E. coli. Comparison with other DHOdehase aa sequences showed essentially conservation of the cofactor binding site of flavoproteins. PMID- 1452036 TI - The Rhizobium meliloti pmi gene encodes a new type of phosphomannose isomerase. AB - Interspecific complementation of a Xanthomonas campestris pv. campestris phosphomannose isomerase (PMI) mutant was used to isolate a cosmid from a genomic library of Rhizobium meliloti 2011 carrying the pmi gene of this strain. Subcloning experiments localized the coding region to a 2.0-kb SalI-ClaI fragment. Nucleotide sequence analysis of this fragment indicated the presence of two open reading frames (ORFs), coding for 18- and 43-kDa polypeptides. The analysis of the gene function by gene disruption experiments showed that ORF2 codes for pmi. A comparison of the deduced amino acid sequence with the corresponding sequences of the Pseudomonas aeruginosa and Escherichia coli PMIs revealed no significant homology, indicating that the isolated gene encodes a new type of PMI. The construction of a pmi-deficient mutant of R. meliloti using the sacB-sacR cassette technique showed that the loss of PMI activity does not affect the symbiotic properties of this strain. PMID- 1452037 TI - Cloning and sequencing of the genes encoding glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase and triosephosphate isomerase (gap operon) from mesophilic Bacillus megaterium: comparison with corresponding sequences from thermophilic Bacillus stearothermophilus. AB - The structural genes encoding glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3 phosphoglycerate kinase (PGK) and the N-terminal part of triosephosphate isomerase (TIM) from mesophilic Bacillus megaterium DSM319 have been cloned as a gene cluster (gap operon) by complementation of an Escherichia coli gap amber mutant. Subsequently, the entire tpi gene, encoding TIM, was isolated by colony hybridization using a homologous probe. Nucleotide (nt) sequence analysis revealed an unidentified open reading frame (urf1) of 1029 bp located 50 nt upstream from the start codon of the gap gene. Gene expression from subclones containing different coding regions was studied by enzyme assay and SDS-PAGE. Both GAPDH and TIM are synthesized in transformed E. coli cells, whereas PGK is not. There is no unequivocal evidence for urf1 expression. Two putative promoter sites are present: one 100 nt upstream from urf1 and one 200 nt upstream from the pgk gene. An inverted repeat following the second promoter site is postulated to be involved in the transcriptional regulation of the operon. Each coding region shows a G+C content of 40% attained by the adaptation of the G+C content of the third base in the codon to compensate the G+C content of the first and second bases. The deduced amino acid (aa) sequences of B. megaterium GAPDH, PGK and TIM were compared with those from the thermophilic Bacillus stearothermophilus by antisymmetrical matrices. The detected characteristic thermophilic-mesophilic exchange pattern concerning aa substitutions between hydrophobic-polar and charged-charged residues corresponds to data obtained for thermophilic and mesophilic lactate dehydrogenases (LDH). The determination of the thermostability of these enzymes revealed two regions of stability for B. megaterium TIM at high enzyme concentrations. Heat treatment seems to be responsible for the conversion of two differently active conformations or the induction of a new quaternary structure. PMID- 1452038 TI - Four genes in Streptomyces aureofaciens containing a domain characteristic of principal sigma factors. AB - Four genes encoding sigma-factor-like proteins, hrdA, hrdB, hrdD, and hrdE, were identified in a Streptomyces aureofaciens genomic library using an oligodeoxyribonucleotide probe encoding a peptide motif homologous to the core binding domain in sigma factors. The deduced proteins have M(r) values of 43,363, 57,172, 36,591, and 57,565, respectively, and strongly resemble all known principal sigma factors, including possession of the characteristic 'rpoD box'. Transcription analysis of the hrd genes by Northern blot hybridization indicated only the expression of hrdB and hrdD and weak transcription of hrdA. A repetitive region of a pentapeptide tandemly repeated 6 and 4 times was identified in the N terminal part of HrdB and HrdE, respectively. No such domain was found in any principal sigma factors. PMID- 1452039 TI - tDNA(ser) sequences are involved in the excision of Streptomyces griseus plasmid pSG1. AB - Plasmid pSG1 is maintained in some derivatives of Streptomyces griseus NRRL3851 mainly in the chromosomally integrated form (pSG1int). In others, the integrated plasmid is co-maintained with free pSG1 [Cohen et al., Plasmid 13 (1985) 41-50]. The pSG1 plasmid integration site (attP) and the pSG1int-chromosome boundaries (attL and attR) were cloned and sequenced. The results indicate that pSG1int is flanked at attL by a functional tRNA(ser) gene and at attR by a 60-nt sequence of the 3' end of the same tRNA(ser) gene. A single mismatch distinguishes the 60-nt sequence at attR from its direct repeat at attL. The attP site contains a single copy of the 60-nt repeat, identical to the one at attL. This observation indicates that pSG1, like integrating plasmids of other Actinomycetes, is integrated in a tRNA gene and suggests that the exact excision of pSG1int occurs by a recombinational crossing-over event at the first 43 nt of the 60-nt repeat. PMID- 1452040 TI - Transcription map of the early region of the Streptomyces bacteriophage phi C31. AB - Streptomyces coelicolor A3(2), lysogenised by the temperature-sensitive cts1 mutant of phi C31, can be synchronously induced into the lytic cycle by heat treatment. A transcription map of 10 kb of the phi C31 early gene cluster was deduced using low-resolution S1 nuclease mapping of RNA prepared 10 min after induction. At least nine early transcripts, early (e)RNAs 1-9, were localised reading exclusively rightwards with respect to the standard physical map of phi C31. The mRNAs were extensively overlapping, frequently initiating at the same place but terminating at different sites, and vice versa. Gene expression during the lytic cycle was tightly regulated; no transcription was observed before induction. Transcription was maximal at 10 min post-induction, and at 20 min, eRNAs 5 and 6 persisted whilst eRNAs 7-9 were severely reduced or absent. The pattern of transcription of the early region is consistent with the simultaneous activation of a large number of promoters and differential termination efficiency. PMID- 1452041 TI - A method for generating transcripts with defined 5' and 3' termini by autolytic processing. AB - Plasmids containing both the hammerhead and hairpin ribozyme autocatalytic cassettes were constructed for the purpose of generating RNA transcripts with specific termini at both the 5' and 3' ends. Following transcription, the RNA encoded by these cassettes was capable of intramolecular cleavage. This resulted in the generation of a processed RNA, which was located between the two cassettes, with specifically engineered 5' and 3' ends. The two different ribozymes were selected for their efficient intramolecular cleavage ability and to reduce the possibility of DNA recombination that could occur if identical cassettes were used. An application of this technique was the generation of a processed RNA which was itself a ribozyme, with specific 5' and 3' termini. The ribozyme generated was a hairpin ribozyme specific for a sequence in the gene encoding hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoA reductase). The processed ribozyme was fully catalytically active against an RNA substrate sequence of HMGCoA reductase. PMID- 1452042 TI - Histone-like proteins are required for cell growth and constraint of supercoils in DNA. AB - The gene hns of Escherichia coli K-12, which encodes the histone-like protein H NS, was inactivated by insertion of a DNA (gene hph) encoding hygromycin phosphotransferase. The growth rates of two mutants lacking either one or the other of the histone-like proteins, HU and IHF, were not affected by introduction of the hns mutation. However, cells depleted of HU, IHF and H-NS simultaneously, could not be constructed by P1 phage-mediated transduction. These results, together with our previous finding that cells deficient in both HU and IHF are viable at 30-37 degrees C [Kano and Imamoto, Gene 89 (1990) 133-137] showed that E. coli cells deficient in any two of these three histone-like proteins are viable at 30-37 degrees C, and suggested that simultaneous deficiency of all three of the proteins is lethal. There were no detectable differences in the levels of superhelicity of the reporter plasmids isolated from cells deficient in either IHF or H-NS, or from wild-type cells, but about 15% decrease in negative superhelicity was detected for the reporter plasmid isolated from cells lacking HU and lacking both HU and H-NS. However, the cryptic bgl operon, whose expression was reported to be regulated through topological changes of cellular DNA, could not be activated in cells depleted of HU or IHF. The bgl operon was expressed in cells depleted of both HU and H-NS as well as in cells depleted of H NS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452043 TI - The mosaic organization of the mitochondrial introns of Saccharomyces cerevisiae: features and evolutionary origins. AB - The introns of three genes (oxi3, cob and 21S) from the mitochondrial (mt) genome of Saccharomyces cerevisiae contain closed reading frames (CRFs). In the present work, we have analyzed these sequences in their oligodeoxyribonucleotide (oligo; isostich) patterns. We have shown that the relative amounts of di- to hexanucleotides, when compared to random sequences having the same sizes and compositions, exhibit the same deviations as the intergenic noncoding sequences of the mt genome (except for the CRFs from 21S intron). In contrast, intronic open reading frames (ORFs) showed oligo patterns which were generally quite distinct from those of CRFs, although some similarities could be detected in some cases (especially for aI5 alpha). The mt introns of yeast, therefore, are endowed with a mosaic structure, in which CRFs derive from mt intergenic sequences, whereas ORFs have a different origin (indicated as exogenous by other evidences) yet show, in some cases, the effects of 'sequence assimilation' with CRFs. PMID- 1452044 TI - Computer-aided cephalometric tracing and analysis. PMID- 1452045 TI - Pediatric orthodontics. PMID- 1452047 TI - A simple solution to open-bite treatment: retention follow-up. PMID- 1452046 TI - The Bimler appliance--a step by step approach. A case report. PMID- 1452048 TI - The Jasper Jumper technique. PMID- 1452049 TI - The Spahl split vertical appliance. PMID- 1452050 TI - An overview of Twin Block appliance therapy applications. Part 1. PMID- 1452051 TI - A patient "menu" for colored arch-wire ties. PMID- 1452052 TI - The addition of composite to the occlusal surfaces in order to alter condyle/fossa relationships. PMID- 1452053 TI - The Spahl split vertical appliance system. Part 2. PMID- 1452054 TI - An overview of Twin Block appliance therapy applications. Part 2. PMID- 1452055 TI - A comparison of Twin Block, Andresen and removable appliances in the treatment of Class II Division 1 malocclusion. AB - Cephalometric radiographs were taken before and after treatment in three groups of patients. Ten were treated with removable appliance therapy involving extraction of upper first premolars and retraction of anterior teeth. Ten were treated on a non extraction basis coupled with wearing an upper expansion appliance followed by an Andresen appliance. Another group of ten patients were treated in an identical manner except that they wore a Twin Block instead of the Andresen appliance. When comparing the patient groups before and after treatment, statistically significant differences were found for upper incisor angulation in the Removable (t = 9.49 p < 0.001) Andresen (t = 4.48 p < 0.001) Twin Block (t = 2.81 p < 0.001) groups and for angle ANB in the Andresen (t = 2.88 p < 0.01) and Twin Block (t = 2.65 p < 0.01) groups. Thus the overjet was reduced purely by incisor tipping with the removable appliance as would be expected, but both functional appliances produced some bodily correction with an improvement in the dental base relationship. Although the Twin Block appliance group showed a greater reduction in angle ANB this was not significantly different from that in the Andresen appliance group. The treatment time from insertion of the first appliance to reduction of the overjet to 3mm or less was also recorded. The treatment time for the Twin Block group (8.1 months) was significantly less (t = 2.79 p < 0.05) than the Andresen group (12.8 months), but neither functional group differed significantly from the removable appliance group (10.1 months). PMID- 1452056 TI - Diagnostic treatment chart. PMID- 1452057 TI - Achieving excellence in TMJ, functional orthopedics, and case finishing: Part 1. Locating position of maxilla. PMID- 1452058 TI - Truax Clasp-Less appliance system. PMID- 1452059 TI - The Twin Block technique. Part 1. PMID- 1452060 TI - The bicuspid buildup as an alternative in Phase II treatment of craniomandibular dysfunction. PMID- 1452061 TI - Maintaining a positive cash flow in an orthodontic practice. PMID- 1452062 TI - Recontouring teeth for excellence in orthodontic case finishing. Part 1: Air Rotor Slenderizing (ARS). PMID- 1452063 TI - Molecular biology and infections of the gut. PMID- 1452064 TI - Genetic predisposition to alcoholic liver disease. PMID- 1452065 TI - Epidermal growth factor in the oesophagus. AB - Epidermal growth factor (EGF) has been implicated in mitogenesis and oncogenesis in the gastrointestinal tract. To determine the role of EGF in oesophageal disease, its quantity and distribution in the oesophageal mucosa of control subjects and patients with oesophageal disease were studied. Oesophageal biopsy specimens, taken 20-40 cm from the incisors in 72 patients, were graded histologically and adjacent specimens were taken for immunohistochemical analysis of the distribution of EGF. In patients with Barrett's columnar lined oesophagus, specimens were also taken from the gastric cardia for comparison. Twenty two biopsy specimens showed oesophagitis, 20 Barrett's mucosa, and 30 were histologically normal. EGF was found in the capillary endothelium of the normal oesophageal papillae and basal mucosa. Significantly more EGF positive papillae were found in the normal mucosa (81%) than in the inflamed mucosa (42%) (p < 0.001). The 20 patients with Barrett's mucosa showed abnormal expression of EGF in 25% of the isthmus and superficial epithelial cells. This study has shown that EGF is found only in the endothelial cells of the capillaries of the normal oesophageal mucosa and that the peptide is detectable significantly less frequently than normal in the inflamed oesophageal mucosa. EGF is also abnormally present, in large quantities, in the cytoplasm of the epithelial cells of Barrett's mucosa compared with gastric mucosa. PMID- 1452066 TI - Outcome of surgical treatment of adenocarcinoma in Barrett's oesophagus. AB - A retrospective study was performed of an 11 year period (1978-88) to analyse the survival of 112 patients (85 men and 27 women, mean age 63 years) with adenocarcinoma in a columnar lined (Barrett's) oesophagus in respect of surgical treatment, tumour staging, and histological grading. Presenting symptoms were dysphagia (60%) and pain (25%). Only six patients were previously known to have a columnar lined oesophagus. Eighty five patients (76%) underwent partial resection of the oesophagus and cardia. Postoperative mortality was 6%. After resection (n = 85), the 5 year survival was 24%. Survival was significantly better for patients without regional lymph node metastases (stage 0, I, IIA (n = 61): 5 year survival 30%) and even better if the tumour was restricted to the submucosa (stage 0, I (n = 12): 5 year survival 63%). Survival was not influenced by the histological grade of the tumour. Staging based on infiltration of the oesophageal wall and lymph node spread is valuable in determining the prognosis for patients with adenocarcinoma in Barrett's oesophagus. PMID- 1452067 TI - Endosonography can detect residual tumour infiltration after medical treatment of oesophageal cancer in the absence of endoscopic lesions. AB - Endoscopic ultrasound (endosonography) is useful in the preoperative staging of oesophageal tumours. It may also have a role in evaluation and surveillance of patients with inoperable carcinomas. Thirty four patients with inoperable oesophageal cancer were investigated by endosonography and computed tomography before medical treatment. In 10 patients receiving combined chemotherapy and radiotherapy, the endoscopic lesions resolved and biopsy specimens were negative. When endosonography suggested the persistence of tumour infiltration in these patients, a local recurrence or distant metastases appeared within a few months. In contrast, when no infiltration was detected, no tumoral recurrence or progression was observed within eight months. These results suggest that endosonography is better than endoscopic biopsy specimens and computed tomography in assessing the response of oesophageal carcinoma to non-surgical treatment. PMID- 1452068 TI - Dyspepsia, Helicobacter pylori, and peptic ulcer in a randomly selected population in India. AB - There seems to be a worldwide geographic variation in the prevalence of peptic ulcer disease, although there are few reliable population based studies. This study aimed to determine the prevalence of peptic ulcer disease in a community in southern India and to evaluate the relationship between dyspeptic symptoms, Helicobacter pylori infection, gastritis, and peptic ulcer disease. A sample population was selected randomly from a rural monastic settlement in southern India. Subjects were interviewed using a standardised symptom and demography questionnaire then underwent upper endoscopy and antral biopsy for histology and CLO rapid urease test. Altogether 197 subjects from a population of 1499 (13.1%) were studied. All were male monks and ethnically Tibetan. The median age was 28 years (range: 21-81). None smoked or took NSAIDs. The six month period prevalence of dyspeptic symptoms was 68.5%. Current symptoms were present in 58.9% of subjects. Dyspepsia was more common in subjects aged 40 years or younger (p < 0.0001). H pylori was detected in 77.2% subjects. There was no association between dyspepsia and the presence of H pylori or histological gastritis, although there was a strong correlation between symptoms and ulcer (p < 0.003). The point prevalence of active peptic ulcer was 6.6% (13/197). All ulcers detected were either prepyloric or pyloroduodenal in location. A further 6.6% of subjects had definite evidence of scarring or deformity indicative of ulceration in the past. Subjects with past or present ulcers comprised 17.8% of dyspeptic subjects. H pylori was present in all subjects with active ulcers and in 12/13 of those with scarring. Dyspepsia, H pylori infection, gastritis, and peptic ulcer are all more common in this population than in those from developed countries. Ulcer disease, however, accounts for only a small proportion of subjects with symptoms and neither H pylori infection nor gastritis are significantly associated with the presence of dyspepsia. PMID- 1452069 TI - Mucosal reactive oxygen metabolite production in duodenal ulcer disease. AB - To investigate the hypothesis that reactive oxygen metabolites are important in the pathophysiology of duodenal ulcer disease, their production by duodenal mucosal biopsy specimens was measured using luminol and lucigenin amplified chemiluminescence. Luminol chemiluminescence, expressed as background corrected median photon emission/mg/min x 10(3) (95% confidence intervals), was increased in duodenal inflammation as assessed macroscopically: ulcers 20.3 (4.8 to 51.3), n = 29; severe duodenitis 13.9 (6.6 to 75.3), n = 16; mild duodenitis 0.0 (-0.5 to 0.8), n = 56; controls -0.8 (-1.3 to -0.1), n = 41; p = 0.0001, Kruskal Wallis) and microscopically: severe 17.0 (9.3 to 51.3), n = 12; moderate 0.3 ( 2.8 to 5.8), n = 17; mild -0.1 (-1.8 to 1.0), n = 17; controls -0.8 (-1.6 to 0.0), n = 15; (p = 0.0001). Luminol chemiluminescence was directly related to both the macroscopic and microscopic severity of duodenal damage (Spearman's R = + 0.53, + 0.55 respectively, both p = 0.0001), to histochemical assessment (myeloperoxidase activity) of neutrophil infiltration (R = + 0.63; p = 0.04), and to lucigenin chemiluminescence (R = + 0.56, p = 0.0002). Luminol chemiluminescence was inhibited by sodium azide (-80%), catalase (-73%), and dimethyl sulphoxide (-24%). Superoxide dismutase inhibited lucigenin more than luminol dependent chemiluminescence (-61% and -7% respectively, p < 0.05). Within disease groups, Helicobacter pylori antral infection was associated with increased duodenal chemiluminescence, whereas smoking, alcohol, and use of NSAIDs or H2 blockers had no influence. Their disease related generation in duodenal mucosa supports a role for reactive oxygen metabolites in the pathogenesis of duodenitis and duodenal ulcer. These metabolites might include superoxide, hydrogen peroxide, hydroxyl, and products of myeloperoxidase activity. PMID- 1452070 TI - Effect of immunisation against vasoactive intestinal polypeptide on gastric corpus tone and motility in the ferret. AB - The role of vasoactive intestinal polypeptide in the control of gastric corpus tone and motility was investigated using auto-antibodies to neutralise endogenous vasoactive intestinal polypeptide. Six ferrets were immunised with vasoactive intestinal polypeptide thyroglobulin conjugate in Freund's complete adjuvant which resulted in a significant increase in plasma vasoactive intestinal polypeptide binding activity compared with unimmunised control animals. In acute experiments the level of spontaneous motility in the period immediately after completion of the surgical preparation was 15 times higher in immunised v control animals (p < 0.02). Surprisingly, however, there was no deficit in the ability of the corpus to accommodate fluid. Peak pressure at the end of a 20 ml ramp distension was not different in immunised animals (5.7 (0.6) cm H2O) compared with controls (4.8 (0.3) cm H2O). It is concluded that the non-adrenergic non cholinergic inhibitory mechanisms regulating corpus tone and motility are different and that vasoactive intestinal polypeptide acts primarily to regulate phasic contractile activity. Alternatively, because of plasticity in the mechanisms controlling corpus tone, the effect of vasoactive intestinal polypeptide may have been superceded during the timecourse of the immunisation procedure. PMID- 1452071 TI - Gastric antral dysrhythmias in children with chronic idiopathic intestinal pseudoobstruction. AB - Chronic idiopathic intestinal pseudoobstruction is a serious disorder of intestinal neuromuscular function resulting in recurrent episodes of intestinal obstruction, and is caused by primary disease of the enteric nerves or enteric smooth muscle. Gastric electrical control activity detected by the non-invasive technique of surface electrogastrography was investigated in 11 children (0.1-16 years) with proven chronic idiopathic intestinal pseudoobstruction (four with known disease of the enteric nerves, three with disease of smooth muscle cells, and four without defined pathology), to determine whether abnormalities were present and whether these were useful in detecting the underlying pathology. Abnormalities were present in eight of 11 patients. Persistent tachygastria (electrical control activity frequency > 5 cycles/minute) was found in three patients, all with a proven neuropathy. A continuously irregular frequency was found in five patients, three with a proven myopathy and two with undefined pathology. A normal electrical control activity frequency was present in three patients, one with a proven neuropathy and two with undefined pathology. It is suggested that this non-invasive technique may provide a useful screening test of the pathophysiological basis of the functional obstruction in children with chronic idiopathic intestinal pseudoobstruction. PMID- 1452072 TI - Immunohistochemical analysis of mucosal gamma-interferon production in coeliac disease. AB - The role of gamma-interferon in the pathogenesis of enteropathies with an immunological basis such as coeliac disease, is unclear. Gamma-interferon immunoreactive lymphocytes were quantified in jejunal biopsies from patients with coeliac disease and from normal controls. In coeliac disease, there was an apparent decrease in the percentage of both intraepithelial (3.5% v 13.5%) and lamina propria (10.3% v 47.2%) lymphocytes expressing gamma-interferon compared with controls. In patients successfully treated with a gluten free diet, the percentage of gamma-interferon immunoreactive intra-epithelial lymphocytes was 10.3%. Intraepithelial lymphocytes were immunonegative for class II major histocompatibility complex, while epithelial cells showed increased expression of this product in coeliac disease. The results show that a relatively large proportion of lymphocytes in normal small bowel express gamma-interferon. They also indicate that in coeliac disease the major increase in the numbers of mucosal lymphocytes is the result of infiltration by lymphocytes not expressing gamma-interferon. PMID- 1452073 TI - Gliadin uptake in human enterocytes. Differences between coeliac patients in remission and control individuals. AB - The pepsin trypsin digest of the wheat prolamin gliadin (PT-gliadin) is deleterious to the small intestinal mucosa of coeliac patients. The handling of PT-gliadin by the intestinal epithelium in coeliac patients in remission and control individuals was investigated by in vivo instillation of PT-gliadin. The uptake of PT-gliadin was monitored by immunofluorescence microscopy of intestinal biopsy specimens, using affinity purified PT-gliadin antibodies. Control individuals show weak staining in the apical region of the enterocytes thereby showing an uptake of PT-gliadin. Coeliac patients have a conspicuous fluorescence in relation to the lateral membrane/intercellular space of enterocytes and intense staining intracellularly in the apical region. There is only weak staining in the enterocytes after the instillation was terminated, indicating an intracellular clearance. The study shows that normal enterocytes are able to take up PT-gliadin. The increased uptake in coeliac patients might be of importance for the pathogenesis either by direct toxicity or by presentation to immunocompetent cells. Furthermore, the results are in agreement with the suggestion of a functional alteration in the zonula occludens in the intestinal epithelium of coeliac patients. PMID- 1452074 TI - Colonic preservation reduces need for parenteral therapy, increases incidence of renal stones, but does not change high prevalence of gall stones in patients with a short bowel. AB - Forty six patients with less than 200 cm of normal jejunum and no functioning colon were compared with 38 patients with similar jejunal lengths in continuity with a functioning colon. Women predominated (67%), and the most common diagnosis in each group was Crohn's disease (33 of 46 no colon, 16 of 38 with colon). All patients without a colon and less than 85 cm of jejunum and all those with a colon and less than 45 cm jejunum needed long term parenteral nutrition. Six months after the last resection 12 of 17 patients with less than 100 cm jejunum and no colon needed intravenous supplements compared with 7 of 21 with a colon. Between 6 months and 2 years, little change occurred in the nutritional/fluid requirements in either group, though there was weight gain. Of 71 patients assessed clinically at a median of 5 years, none with more than 50 cm of jejunum and a colon needed parenteral supplements. Most (25 of 27) of those without a colon who did not need parenteral supplements required oral electrolyte replacement compared with few (4 of 27) with a colon. None of the patients without a colon developed symptomatic renal stones compared with 9 of 38 (24%) with a colon (p < 0.001). Stone analysis in three patients showed calcium oxalate. Gall stone prevalence was high but equal in the two groups--43% of those without and 44% of those with a colon. PMID- 1452075 TI - Ketotifen effectively prevents mucosal damage in experimental colitis. AB - The effects of ketotifen, a 'mast cell stabiliser,' on two models of experimental colitis were examined. The inflammatory response elicited by either trinitrobenzene sulphonic acid or acetic acid resulted in increased colonic synthesis of platelet activating factor, prostaglandin E2, thromboxane B2, leukotrienes B4 and C4, and myeloperoxidase activity. Intragastric administration of ketotifen 100 micrograms/100 grams twice daily significantly decreased mucosal damage when given prophylactically 48 hours before the induction of colitis and then throughout the experiment. This effect was consistent in both models and was accompanied by a significant reduction in mucosal generation of platelet activating factor, prostaglandin E2, thromboxane B2, and leukotrienes C4 and B4. Myeloperoxidase activity was reduced as well, reaching significance only in the acetic acid model. This study shows that both trinitrobenzene sulphonic acid and acetic acid colitis can be pharmacologically manipulated by ketotifen. The mechanism of action of ketotifen has not yet been determined. Ketotifen's potential in the treatment of active inflammatory bowel disease or in the prevention of exacertations, or both, remains to be elucidated. PMID- 1452076 TI - Predictors of presence, multiplicity, size and dysplasia of colorectal adenomas. A necropsy study in New Zealand. AB - Three hundred and thirty six forensic necropsy specimens of large bowel were examined in order to identify subject related variables that independently predicted the following adenoma characteristics: presence, size (largest), multiplicity and high grade dysplasia. The variables were age, gender, body mass index, race (European origin versus Maori/Polynesian) and presence of hyperplastic (metaplastic) polyp(s). Subjects included 303 New Zealanders of European origin (M = 185, F = 118) yielding 149 adenomas and 251 hyperplastic polyps and 33 Maori/Polynesians (M = 25, F = 8) yielding five adenomas and one hyperplastic polyp. Independent predictors of adenoma presence as determined by regression analysis were age (p = 0.0001), presence of hyperplastic polyps (p = 0.0001) and male gender (p = 0.05). Models were poor at explaining variation in size, multiplicity, and dysplasia. Larger adenomas occurred more frequently in subjects with multiple adenomas (p = 0.03) and multiple adenomas were probably associated with hyperplastic polyps (p = 0.09) and male gender (p = 0.09) in Europeans. High grade dysplasia was more frequent in women (p = 0.05) and possibly in subjects with hyperplastic polyps (p = 0.2). Body mass index and ethnicity did not predict any adenoma characteristics, but hyperplastic polyp prevalence was influenced by European origin (p = 0.04) and to a lesser extent by body mass index (p = 0.08) as well as presence of adenoma (p = 0.0002) and age ( = 0.005). The association of hyperplastic polyp with presence, multiplicity but not size of adenoma and with a high risk group for colorectal cancer (New Zealanders of European origin) suggests that the hyperplastic polyp serves as a marker for a factor which influences neoplastic evolution at the stages of initiation/transformation but not promotion. Fifty nine per cent of individuals with adenoma(s) did not have hyperplastic polyp(s) emphasising that the last would serve only as a marker of populations and not individuals at high risk of bowel cancer. Low intracolonic butyrate may be the factor linking the expression of the two types of polyp. PMID- 1452077 TI - Dietary calcium does not reduce experimental colorectal carcinogenesis after small bowel resection despite reducing cellular proliferation. AB - It has been proposed that colorectal carcinogenesis is accompanied by increased mucosal cell proliferation and that the converse may also apply. To examine this thesis, the crypt cell production rate (CCPR) was measured in eight groups of rats (n = 187) that had received 1,2 dimethylhydrazine, 70% small bowel resection, supplemental dietary calcium, or a combination of these. Analysis of variance showed the following: (1) the CCPR decreased between the ileum and distal colon; (2) the CCPR decreased between 16 and 32 weeks; (3) 1,2 dimethylhydrazine and small bowel resection increased the CCPR and calcium decreased the CCPR independently of one another; (4) the CCPR interacted with 1,2 dimethylhydrazine x small bowel resection, calcium x 1,2 dimethylhydrazine and interacted between the site of bowel and calcium, 1,2 dimethylhydrazine, small bowel resection, and 1,2 dimethylhydrazine x small bowel resection (p = 0.014 to p < 0.001). The tumour yield was reduced by calcium in 1,2 dimethylhydrazine treated animals (chi 2 = 14.1, df = 3, p < 0.01) but was unaffected by calcium in 1,2 dimethylhydrazine and small bowel resection treated animals despite significant differences in the CCPR. An increase of the CCPR both preceded and accompanied colorectal carcinogenesis but reduction of the CCPR was not invariably accompanied by reduced carcinogenes. PMID- 1452078 TI - Crypt cell production rates at various sites around the colon in Wistar rats and humans. AB - The crypt cell production rate (CCPR) is considered the most robust estimate of cell turnover. The CCPR was determined at various sites around the colon in the Wistar rat (using an in vivo technique) and in six healthy humans (using in vitro organ culture). In both the rat and human colon, the CCPR increased proximally from the rectum to the caecum. The caecum had a significantly higher cell turnover than any other site in the colon (p < 0.05 in the rat, p < 0.01 in humans, Student's t test). These findings are of interest when considering cellular proliferation studies in both inflammatory bowel disease and colorectal cancer, and draw attention to the importance of choosing a constant reference site for comparative studies. This is the first time the CCPR had been measured along the length of the human colon. PMID- 1452079 TI - Anorectal function in patients with complete supraconal spinal cord lesions. AB - Anorectal manometry and sphincter electromyography were performed in 23 patients with complete supraconal traumatic spinal injuries and 30 age and sex matched control subjects. Basal pressures in the spinal group were similar to those in normal subjects but conscious control of sphincter activity was abolished in all spinal patients. Discriminant rectal sensation was also abolished during rectal distension, but 40% of patients experienced a dull pelvic ache at maximum levels of distension. Phasic rectal contraction and anal relaxation were present but exaggerated and induced at lower distending volumes than in normal subjects. The configuration of the rectal pressure/volume relationship was linear in patients compared with a reversed 'S' shape in normal subjects. The external anal sphincter response to rectal distension was noticeably attenuated, reinforcing the view that this spinal reflex is heavily modulated by supraspinal centres under normal circumstances. The external anal sphincter response to increases in abdominal pressure was also attenuated, and the anal pressures were strongly correlated with the level of the lesion and the abdominal pressure the patient could generate. No spinal patient showed a decrease in external anal sphincter activity during straining 'as if to defecate.' The exaggerated anorectal smooth muscle responses to rectal distension and the attenuated external sphincter response explain why patients with complete supraconal spinal lesions experience uncontrollable reflex defecation, while the persistance of external and sphincter contraction and the absence of any external anal sphincter relaxation during straining 'as if to defecate' might explain the difficulty that these patients have in consciously expelling rectal contents. PMID- 1452080 TI - Detection of subclinical autonomic neuropathy in constipated patients using a sweat test. AB - Chronic idiopathic constipation may be the result of an autonomic neuropathy. This hypothesis was tested in 23 constipated patients and 17 age matched controls, using the acetylcholine sweat spot test devised to test autonomic integrity in diabetes. Acetylcholine (0.01%) was injected in the dorsum of the foot painted with a mixture of starch and iodine. Active sweat glands appeared on the surface of the skin as small black dots which were photographed and counted, using a grid with 60 subareas. Two measurements were made: the number of dots per unit subarea (sweat spot test score) and the % number of abnormal subareas (with less than six spots). These two parameters were correlated. The median sweat spot test score was 9.53 in patients and 13.92 in controls (p = 0.0001), the receiver operating characteristic curve showing that a score of 12 delimited normal and abnormal subjects. Increasing age was correlated with a low score in patients, probably because of prolonged symptoms. Seventy per cent of patients and one control had a borderline or abnormal number of subareas. These results suggest that idiopathic constipation is associated with a degree of autonomic denervation. The sweat spot test is an easy, inexpensive method to test this hypothesis and deserves a place in the clinical assessment of slow transit constipated patients. PMID- 1452082 TI - Plasma concentrations of endogenous heparinoids in portal hypertension. AB - Bleeding as a complication of liver disease can occur in the absence of recognised haemostatic defects. It is now possible to measure the concentration of endogenous heparinoid substances in the blood using a competitive binding assay. One such substance, heparan sulphate (normal range < 600 ng/ml) was assayed in the plasma of 49 patients admitted because of oesophageal varices. In 27 patients with recent upper gastrointestinal bleeding the median plasma heparan sulphate value was 1700 ng/ml (interquartile (IQ) range 900-3900) compared with 390 ng/ml (IQ range 256-800) in 22 patients with no recent bleed (p < 0.01). As heparan sulphate is metabolised by the same route as exogenous heparin, an attempt to establish a cause for the raised heparan concentrations was made by measuring the clearance of exogenous heparin in 10 portal hypertensive patients and 10 controls. The median half life of heparin in plasma in the portal hypertensive patients (25.5 minutes; IQ range 22-34) was significantly longer (p < 0.007) than the median half life in the controls (18.7 minutes; IQ range 17 21.5). Thus, there is evidence of raised concentrations of endogenous heparin like substances in portal hypertensive patients after gastrointestinal bleeding. These high concentrations may result from reduced hepatic clearance. PMID- 1452081 TI - Intrahepatic expression of pre-S1 and pre-S2 antigens in chronic hepatitis B virus infection in relation to hepatitis B virus replication and hepatitis delta virus superinfection. AB - Hepatocyte expression of pre-S1 and pre-S2 in relation to hepatitis B virus replication (hepatitis B virus-DNA in serum and HBcAg in the liver), histological activity and hepatitis delta virus superinfection was studied by indirect immunofluorescence on frozen sections of liver specimens from 68 patients with chronic hepatitis B virus infection. All 44 patients with chronic type B hepatitis had pre-S1 and pre-S2 display in the liver. The distribution of pre-S1 in the liver was membranous in one, mixed membranous and cytoplasmic in 12, and cytoplasmic in 31. The distribution of pre-S2 was membranous in one, mixed membranous and cytoplasmic in 26, and cytoplasmic in 17. Membranous expression of pre-S1 was significantly more prevalent in patients with active hepatitis B virus replication than in those without (13/28 v 0/16, p < 0.001), regardless of the histological activity, as was membranous expression of pre-S2 (27/28 v 0/16, p < 0.001). In contrast, a significantly higher extent of cytoplasmic expression of pre-S1 and pre-S2 was noted in patients without active hepatitis B virus replication than in those with. Of 24 patients with chronic type D hepatitis virus, eight had active hepatitis B virus replication, and the other 16 did not. The distribution and quantitative expression of pre-S1 and pre-S2 in the liver in these patients also correlated significantly with the status of hepatitis B virus replication and, moreover, showed little or no difference from those without hepatitis delta virus infection. In conclusion, all patients with chronic type B hepatitis had synthesis and display of pre-S1 and pre-S2 in the liver. The distribution and quantitative expression of pre-S1 and pre-S2, however, were closely related to the status of hepatitis B virus replication, but not to the histological activity. Hepatocyte expression of pre-S1 and pre-S2 in chronic type D hepatitis also correlated significantly with status of hepatitis B virus replication, and was not modulated by concurrent hepatitis delta virus infection. PMID- 1452083 TI - A prospective trial of endoscopic sclerotherapy v oesophageal transection and gastric devascularisation in the long term management of bleeding oesophageal varices. AB - In a prospective three centre study oesophageal transection and gastric devascularisation have been compared with endoscopic sclerotherapy in the long term management of bleeding oesophageal varices. Cirrhotic patients (Child's A or B grade) with documented bleeding oesophageal varices were treated initially with emergency sclerotherapy, and after five days stability, were allocated to one of the two treatment regimes. The endoscopic sclerotherapy group underwent regular sclerotherapy until variceal obliteration while those undergoing surgery were not endoscoped unless bleeding recurred, when they were treated by sclerotherapy if appropriate. Ninety two patients were eligible for analysis (68% alcoholic cirrhosis; mean age 50.1 years) and follow up was achieved for a mean of 52.5 months (range 17-83). Mortality in the first three months was greater in the oesophageal transection and gastric devascularisation group (20% v 1%) but by two years the survival curves were the same and thereafter there was no difference in mortality. Rebleeding occurred in 13/41 (31%) patients, undergoing oesophageal transection and gastric devascularisation. The costs incurred during the first year of oesophageal transection and gastric devascularisation treatment were significantly greater than with endoscopic sclerotherapy (4369 pounds v 1067 pounds, p < 0.0001) and the high rate of rebleeding in the surgical group meant that no cost savings occurred in subsequent years. It is concluded that oesophageal transection and gastric devascularisation confers no benefit over endoscopic sclerotherapy in terms of long term survival and that it is not cost effective as judged by the current health care costs in the United Kingdom. PMID- 1452084 TI - Value of ultrasound and liver function tests in determining the need for endoscopic retrograde cholangiopancreatography in unexplained abdominal pain. AB - The value of serum liver function tests and abdominal ultrasound as screening tests of the need for endoscopic retrograde cholangiopancreatography (ERCP) was determined in patients with unexplained abdominal pain without associated jaundice. In 1989 and 1990 1005 ERCPs were undertaken, of which 138 (14%) were for this indication. The duct or ducts of interest were delineated by ERCP in 95% of patients. The lesions found were bile duct stones in 10 patients, chronic pancreatitis in five, pancreatic carcinoma in one, peptic ulcer or duodenitis in four. A satisfactory ultrasound examination had been performed in 94% of patients. For chronic pancreatitis, its sensitivity was 60% and specificity 95%. For choledocholithiasis, the ultrasonic detection of duct dilatation or stones had a sensitivity of 90% and specificity of 86%. Of the liver function tests, the alkaline phosphatase was more sensitive (67%) than the transaminases (44%) in indicating the presence of bile duct stones and had a high specificity (95%). None of the 10 patients with duct stones had normal ultrasound and normal alkaline phosphatase. Thus it was found that demonstration of a normal common bile duct by abdominal ultrasound and normal serum alkaline phosphatase together have 100% specificity in excluding bile duct stones. Using such knowledge over the two year period of this study would have spared 36 patients the need for ERCP. PMID- 1452085 TI - Intracerebroventricular neuropeptide Y stimulates bile secretion via a vagal mechanism. AB - The effect of intracerebroventricular injection of neuropeptide Y on biliary secretion was studied in conscious dogs, prepared with gastric and duodenal fistulas and cerebroventricular guides. Bile secretion was increased in a dose dependent fashion by intracerebroventricular neuropeptide Y. The peak increase was seen after 500 pM/kg of neuropeptide Y which resulted in a 30 x 2% increase in bile flow over the period 30-150 minutes after injection. ( CONTROL: 23 x 2 (1 x 2) ml/2 hours; neuropeptide Y 500 pM/kg: 30 x 5 (1 x 1) ml/2 hours). Biliary lipid composition was not altered significantly but bicarbonate output was increased at all doses tested. Intravenous infusion of neuropeptide Y (1000 pM) for 1 hour had no significant effect. Intracerebroventricular neuropeptide Y (1000 pM/250-300 mg body weight) also increased bile flow in urethane anaesthetised rats. This effect was abolished by cervical vagotomy. The demonstration of a central stimulation of alkaline bile flow suggests that bile secretion may be subject to central modulation. PMID- 1452086 TI - Minimal change chronic pancreatitis. AB - In patients with severe abdominal pain, of pancreatic origin, there are a few with minimal or equivocal findings on pancreatic investigation and in whom the aetiology of their pancreatic disease is elusive. The findings and outcome in 16 of these patients (four men and 12 women) who underwent resection are reported. Pancreatic imaging showed minimal or equivocal findings in all 16; pancreas divisum was present in five. All were managed conservatively at first but resection was required for progression of symptoms. A drainage procedure was performed initially in five patients but relief of pain was at best transitory before further surgery was required. Partial resection was needed in 12, of whom eight required subsequent completion pancreatectomy and four had a one stage total resection. Nine patients are currently pain free after resection or are very much improved, while six are no better and one patient has died from an unrelated cause. Histology of resected specimens showed chronic inflammatory changes accompanied by subtle non-inflammatory changes in all but one. These changes include duct proliferation, duct complex formation, adenomatous nodules, and acinar cell atrophy, the significance of which is unclear. These findings suggest a syndrome of minimal macroscopic and radiological change chronic pancreatitis with pain as its chief clinical feature and a distinct histology, the aetiology of which is unclear. It seems that there is a distinct syndrome of minimal change pancreatitis, among the group of patients which presents with the clinical features of chronic pancreatitis. PMID- 1452087 TI - Effective treatment of diabetic diarrhoea with somatostatin analogue, octreotide. AB - A 22 year old insulin dependent diabetic with high volume, secretory chronic diarrhoea refractory to standard andiarrhoeal drugs was treated with the somatostatin analogue octreotide, 50 micrograms twice daily by subcutaneous injection. She improved markedly with a decrease in mean stool weight from 1170 g/24 h range 440-2900 g) to 440 g/24 h (range 180-800 g) (p < 0.05). Stool frequency also decreased from six (range two to 12) to one (range one to three) bowel movements per day (p < 0.01). Mouth to caecum transit time increased from 45 minutes to > 210 minutes, although total gut transit time was unchanged and remained rapid at nine hours. Thus octreotide can reduce stool volume and frequency in high volume diabetic diarrhoea when conventional antidiarrhoeal agents have failed. Its therapeutic benefit appeared to be predominantly related to a marked increase in mouth to caecum transit time. PMID- 1452088 TI - Hepatic aberrations in patients with chronic pancreatitis. PMID- 1452089 TI - Helicobacter pylori infection rates in relation to age and social class in a population of Welsh men. PMID- 1452090 TI - Cholestatic hepatitis associated with clavulanic acid. PMID- 1452091 TI - Pugh's grading in the classification of liver decompensation. PMID- 1452092 TI - Superior mesenteric blood flow. PMID- 1452093 TI - The possibilities of changing the production of exocellular polysaccharides of a mutant Mycobacterium strain. AB - By second-step mutagenesis and treatment with N-methyl-N'-nitro-N nitrosoguanidine a mutant strain of Mycobacterium sp. V-649 producing a glucan extracellular polymer and another new streptomycin-resistant mutant were prepared. This mutant strain formed more than 100% first-rate (1.0-1.2%) exocellular polysaccharide. Treatment with 1% dimethyl sulfoxide during submerged cultivation of the mutant strain did not increase the production of the extracellular polysaccharide. PMID- 1452094 TI - Virulence of silver-resistant mutant of Klebsiella pneumoniae in burn wound model. AB - A silver-resistant mutant of Klebsiella pneumoniae B-5 was produced by passaging in nutrient broth containing graded concentrations of silver nitrate up to 150 ppm. The development of silver resistance in the strain resulted in rough colonies, decrease in cell size, carbohydrate content and change in klebocin pattern. The virulence of the AgR strain as checked by the burn wound model decreased as the mutant could not establish itself in the skin and spleen of the animals and the organism was cleared more efficiently by human lymphocytes than the parent AgS strain. PMID- 1452095 TI - Immobilized beta-glucosidase from Curvularia lunata. AB - beta-Glucosidase from Curvularia lunata was immobilized in pellets of polyacrylamide, sodium alginate and agar. The activity of the enzyme was estimated at different times by measuring the absorbance of a solution into which 2-nitrophenol was released by the enzyme. The effect of pH and temperature was studied to select the optimum conditions. Thermostability of the beta-glucosidase in each of the carriers was assessed over a period of 12-26 d. The immobilized enzyme on all the three carriers retained its activity longer than free enzyme did. Polyacrylamide was the best carrier both in terms of thermostability and of reusability of the immobilized enzyme preparations. The Michaelis constant (Km) for each of the immobilized enzyme preparation was calculated. PMID- 1452096 TI - UV-induced mutability in repair-deficient rad6-1 strains of Saccharomyces cerevisiae is caused by a suppressor gene. AB - The RAD6 gene is a multifunctional gene required for DNA repair, induced mutagenesis and sporulation. The survival and revertibility of two loci in four rad6-1 mutant strains of different origin after UV irradiation were followed. As expected, all the rad6-1 strains tested were more sensitive to UV radiation in comparison with RAD6 strains. The reversion frequency per survivor in trp1-289 and arg4-17 alleles was significantly higher in all four rad6-1 mutant strains than in wild-type strains after equal doses of UV radiation. On the basis of genetic analysis we suggest that the phenomenon of increased frequency of induced mutagenesis is caused by a suppressor gene. PMID- 1452097 TI - Expression of Japanese quail ovalbumin in Saccharomyces cerevisiae. AB - A cDNA sequence coding for Japanese quail ovalbumin was used for the construction of expression plasmid under the ADH1 promoter of the yeast shuttle vector pVT101 U. The resulting recombinant expression vector pJK2 was used for the transformation of Saccharomyces cerevisiae. Expression of quail ovalbumin in yeast cells was demonstrated by Western blotting followed by immunochemical detection. PMID- 1452098 TI - Intrapopulation variability of antibiotic biosynthesis in streptomycetes. AB - Spontaneous variants making up parallel series of hereditary variability inside the populations of antibiotic-producing actinomycetes differ in the level of their antibiotic activity. As a rule, spontaneous variants of the basic type possess the highest antibiotic activity. Other variants representing parallel series have a lower activity level. This raises the possibility to carry out a directed selection of previously known active colonies from populations on the basis of their easily discernible morphological properties. It enhances the efficiency of selection work both in the case of stabilization of the level of antibiotic activity and in the case of obtaining more productive commercial strains. PMID- 1452099 TI - Ethanol-induced death and lipid composition of Saccharomyces cerevisiae: a comparative study of the role of sterols. AB - Ethanol tolerance of four Saccharomyces cerevisiae strains characterized by different amounts of delta 5,7-sterols was tested. The individual tolerances did not correlate with the strains sterol levels. The highly and medium-accumulating strains exhibited the highest and lowest ethanol tolerances, respectively. PMID- 1452100 TI - The K3 type killer strains of genus Saccharomyces for wine production. AB - Using simultaneous fusion of protoplasts of three strains the auxotrophic K3 killer designated MH1 was prepared at a very low frequency and further employed for the transfer of the K3 killer character into a commercial wine yeast. A novel Saccharomyces Bratislava 1K3 strain with desirable technological and anti-yeast killer abilities was thus constructed. Attempts to prepare double K1/K3 killers were made. The obtained fusion products contained M1 dsRNA and were able to produce only the K1 type killer toxin. PMID- 1452101 TI - Enhanced biodegradation of a hard bis-quaternary ammonium salt. AB - Bacterial strains with a high biodegradation potential were isolated from activated sludge. Their ability to decompose the hard bis-quaternary ammonium salt FB was determined by the method of chemical oxygen demand (COD) in a mineral medium, where the compound FB was the only source of carbon. The COD values were very low after 21 d and in the course of this period they reached zero level twice. The contribution of adsorption to decrease the COD value was small. The maximum COD decrease was accompanied by an increase of cell respiration. It is suggested that FB is effectively decomposed in spite of the fact that according to its structure it is a typical hard detergent. PMID- 1452102 TI - Consumption of a large dose of alcohol in a short time span. AB - Blood alcohol concentrations (BAC) and time to peak BAC were determined in 16 subjects after ingestion of a large quantity of alcoholic beverages within a short drinking time span not exceeding 30 min. The first group (7 subjects) consumed alcohol after a 3- to 4-h fast. In the second group (9 subjects) the consumption of alcohol took place after eating a large meal. Venous blood samples taken 30 min after drinking finished were compared to the near-simultaneous Breathalyzer results. In addition, the minimum duration of a BAC plateau for these drinking circumstances was assessed. PMID- 1452103 TI - Enzyme-linked immunosorbent assay (ELISA) for the determination of the toxic glycoside cleistanthin B. AB - Cleistanthus collinus is a highly toxic plant frequently implicated in suicidal and homicidal poisoning cases referred to our laboratory. An enzyme-linked immunosorbent assay (ELISA) is reported in this paper for the quantitation of the active principles of C. collinus. This method is highly reproducible and sensitive to detect as low as 2 ng/ml of cleistanthin B, a toxic constituent of C. collinus. The ELISA can be successfully applied for the specific identification of C. collinus poisoning in clinical and forensic toxicology. PMID- 1452104 TI - Precision of estimating time of death by vitreous potassium--comparison of various equations. AB - This paper is a study of the precision of estimating the time since death comparing the equations developed by different authors. Our aim is to determine with the maximum degree of accuracy the exact time of death of the individual. We consider that the study has been fully justified by the observed differences in the results obtained from the different equations under study when the concentration of potassium in the vitreous humour was identical. PMID- 1452105 TI - Grading rigor mortis with myotonometry--a new possibility to estimate time of death. AB - Myotonometry has been applied to grade rigor mortis. The myotonometer is a hand held instrument which gives a mechanical impact against the muscle. The muscle responds with a damped vibration which is registered and treated mathematically. The period and the logarithmic decrement of decay of the vibrations were found to change with the development of rigor mortis. The method gives quantitative information on the muscular stiffness and it can be used when estimating the time of death. PMID- 1452106 TI - Bupropion and alcohol fatal intoxication: case report. AB - A fatality due to the ingestion of bupropion and ethanol is presented. Bupropion and its metabolites were extracted from several tissues and identified using gas chromatography with nitrogenphosphorus and mass spectrometry detection. The concentrations of bupropion, hydroxybupropion and the erythroamino and threoamino alcohol metabolites in heart blood were 4.2, 5.0, 0.6 and 4.6 mg/l, respectively. The heart blood ethanol concentration was 0.27 g/dl. In addition, bupropion was distributed as follows: subclavian blood, 6.2 mg/l; bile, 1.4 mg/l; kidney, 2.4 mg/l; liver, 1.0 mg/kg; stomach contents, 16 mg and urine, 37 mg/l. PMID- 1452107 TI - Suicidal hanging in Cardiff--a 15-year retrospective study. AB - A retrospective study of 84 cases of suicidal hanging was undertaken in which petechial haemorrhages or congestion were seen in 27%, soft tissue haemorrhage in 29% and fracture of the hyoid or laryngeal cartilages in 36%. Fractures were found to be related to increasing age and were not found when a soft ligature had been employed. Petechial haemorrhages and congestion were related to the completeness of suspension. Apart from the lack of fractures in the soft ligature group any of these findings, either singly or in combination, was found to occur without regard to age, suspension type or ligature type. No evidence was found of clustering or seasonality. The findings are compared to other series and discussed with regard to the mechanisms of causation. PMID- 1452108 TI - Determination of cocaine and benzoylecgonine in human amniotic fluid using high flow solid-phase extraction columns and HPLC. AB - A new solid-phase extraction procedure for the determination of cocaine and benzoylecgonine in amniotic fluid, using high flow co-polymeric sorbents is reported. The recoveries of cocaine and benzoylecgonine within the range 0.1-1 mg/l were 95.7% and 50.3%, respectively. The use of high-flow sorbents allowed the easy extraction of amniotic fluid regardless of sample viscosity or physical nature. The use of these solid-phase columns provided many advantages over the more commonly used solvent extraction, including an increase in extraction speed and efficiency, reduced operator time, reduced solvent use and disposal volumes and exceptional extract quality. Further, the determination of amniotic fluid obtained from pregnant cocaine users may provide important information about handling of cocaine by the fetus at various gestational ages. The procedure was successfully applied to amniotic fluid from suspected cocaine abusers. PMID- 1452109 TI - A matter of large body passing through a small hole: the holeproof out the window. AB - A baffling case of fall-from-height is described focusing on aspects of a human body passing through a small hole, within a holeproof window. It is a classic example of an unsatisfactory outcome when a scene of death is modified adversely due to delay in the commencement of scene management. The operative factors may be entirely outside the control of scene investigators. The primary medical attendant is reminded of the forensic obligations at a scene of unnatural death. Reporting this case might encourage forensic practitioners having experience of a similar case to respond through this journal. PMID- 1452110 TI - Early and late meningeal reaction to trauma after long-term brain death. AB - We examined histologically the meninges adherent to traumatic lesions of a patient with brain death sustained for 101 days and observed both early and late reactions of wound healing at the same site of the dura mater. Some parts of the dura mater were thick and histological examinations revealed formation of new vessels and fibrosis with strong positive reaction for iron and fat staining. We also observed fresh haemorrhage and some cell infiltration in the dura and fresh haemorrhage in a small piece of necrotic brain tissue adhered to the dura mater, while other areas of the brain tissue were completely necrotic, enabling the sites of head injury to be localised. These observations suggested that the blood flow in the dura mater fluctuates due to a change of microenvironment, which probably causes repeated secondary petechial haemorrhages in the dura and its adherent necrotic brain tissue, even 101 days after brain death. PMID- 1452111 TI - Widespread myocardial and pulmonary bone marrow embolism following cardiac massage. AB - Widespread fatal massive bone marrow embolism of the coronary and the pulmonary arteries are described in a 71-year-old man with a respiratory disease. Cardiac massage was carried out during the cardiac arrest. In autopsy findings there were no fractures of the ribs or the sternum. The authors suggested that the cardiac massage was the most important predisposing factor for the bone marrow embolism. PMID- 1452112 TI - Post-mortem toxico-kinetics of trazodone. AB - Trazodone is a structurally unique bicyclic anti-depressant, said to be significantly less toxic than other anti-depressants following an acute overdose. We studied the tissue distribution and post-mortem redistribution of trazodone in two fatalities, one of which allowed comparison with trimipramine, a typical tricyclic anti-depressant. Case 1, a 53-year-old female weighing 72 kg, had femoral vein concentrations of trimipramine 5.5 micrograms/ml, trazodone 14.4 micrograms/ml and alcohol 107 mg%. Case 2, a 48-year-old female of 70 kg, had a femoral vein trazodone of 15.5 micrograms/ml and alcohol 34 mg%, with no other drugs detected. For case 1 and case 2 respectively, trazodone tissue concentrations were: skeletal muscle 7.3 and 9.0 micrograms/g; left and right lungs 13.3, 12.9 and 35.3, 40.1; myocardium, 30.9 and 28.9; kidneys 34.7 and 39.6; liver 73.7 and 82.4; fat 18.5 and 16.5; brain 48.6 and 20.9. For case 1 and 2, respectively, blood trazodone concentrations in 10 initial autopsy samples ranged from 13.7-17.3 and 14.4-16.9 micrograms/ml. Twenty-four and forty-eight hours later the respective ranges were 12.8-18.0 and 12.4-19.9 for case 1, 12.5 20.1 and 12.7-27.0 for case 2. By contrast, for trimipramine, blood concentrations at 0 time, 24 h and 48 hours ranged from 5.5-11.4, 5.2-14.3, and 4.2-18.2, respectively. We conclude that trazodone shows little preferential concentration in solid organs and consequently has relatively stable post-mortem blood concentrations with little drug redistribution artefact. Both the clinical pharmacokinetics and post-mortem toxicokinetics of trazodone differ significantly from the tricyclic anti-depressants. PMID- 1452114 TI - Influence of paracetamol, sulfanilamide and ascorbic acid on the electrocatalytic glucose sensor. AB - An electrocatalytic glucose sensor for in vivo application has been developed. The principle of measurement is based on the direct electrochemical oxidation of glucose at a platinum electrode without an enzymatic reaction. In an in vivo experiment with sheep the glucose sensor was tested with respect to its cross sensitivity towards ascorbic acid, paracetamol and sulfanilamide. The influence of these substances could be reduced by an adapted calibration to such an extent, that the sensor performance could be ensured. PMID- 1452113 TI - Insulin modulation of chronotropic response to Adrenaline in diabetic dogs. AB - In 8 unanesthetized dogs, 10-21 days post pancreatectomy, the cardiac chronotropic response to rapid infusion of a pharmacological dosage of Adrenaline was begun. During the subsequent month, the response was recorded electrocardiographically on 19 occasions. On 8 occasions, animals were treated with continuous intravenous administration of fluids and insulin up to the time of the test; on 11, insulin was omitted for 18 hours before Adrenaline injection. Insulin treated animals responded with the typical brief initial bradycardia, followed by some 2 minutes of ventricular tachycardia, and restoration of preinjection heart rate and electrocardiograph pattern within 5 minutes. On those occasions when insulin was omitted, the tachycardia was replaced by ventricular bradycardia. The altered chronotropic response of non-insulin treated dogs indicates impairment of their cardiac beta receptors. PMID- 1452115 TI - Protective effect of diltiazem hydrochloride on the occurrence of alloxan- or streptozotocin-induced diabetes in rats. AB - This study demonstrated that 20 mg/kg of the Ca2+ channel blocker, diltiazem hydrochloride, administered by intraperitoneal injection 15 min before 200 mg/kg of alloxan given by the same route to induce diabetes, served to suppress disease onset completely in rats. Even though 48-h fasting promoted the onset of alloxan diabetes, 40 mg/kg of diltiazem hydrochloride completely prevented the occurrence of diabetes induced by intraperitoneal injection of 200 mg/kg of alloxan. Forty mg/kg of the same agent, however, failed to prevent the onset of diabetes induced by the intravenous injection of streptozotocin (50 mg/kg). From the fact that Ca2+ channel blockers such as nicardipine, verapamil and bepridil have a similar suppressive effect on the occurrence of alloxan diabetes, one may readily infer that this action is characteristic of Ca2+ channel blockers. Moreover, the results suggest the close connection of Ca2+ in the occurrence of alloxan diabetes in rats. PMID- 1452116 TI - Endurance exercise training causes adrenal medullary hypertrophy in young and old Fischer 344 rats. AB - The purpose of the present investigation was to determine the effects of endurance exercise training on adrenal medullary volume and epinephrine content in young (5 month) and old (23 month) female Fischer 344 rats. Animals from each group underwent 10 weeks of treadmill running (60 minutes per day, 5 days per week). 72 hours following the last training session animals were killed and the adrenal glands removed for subsequent analysis. Plantaris muscle citrate synthase activity increased with training in both young and old animals (39.8% young; 36.4% old). Trained animals had larger adrenal medullary volumes (48% increase in young, and 18% in old) than untrained controls. Trained animals also had higher total adrenal medullary epinephrine content (36% increase in young, and 24% in old). There were no differences in adrenal medullary epinephrine or norepinephrine concentration (micrograms/microliters medulla). It was concluded that the training-induced increase in adrenal epinephrine content is due to an increase in the size of the medulla, and not to a greater medullary epinephrine concentration. Furthermore, similar responses to training occur in both old and young animals. PMID- 1452117 TI - Normal tissue plasminogen activator and plasminogen activator inhibitor activity in plasma from patients with type 1 diabetes mellitus. AB - The fibrinolytic system was investigated in 38 patients (21 males and 17 females) affected by type 1 diabetes mellitus (18 free from complications, 10 with retinopathy, and 10 with autonomic neuropathy) and in 8 healthy controls. Two separate fibrinolysis-stimulating tests were done: standardized venous occlusion and 1-desamino-8-D-arginine vasopressin infusion. Plasma tissue plasminogen activator antigen and activity and plasma plasminogen activator inhibitor activity were measured. All the patients were in good metabolic control (mean HbA1c 7.4%, range 6.1-8.0%). No significant differences were observed either between the diabetic patients and the control subjects, nor among the subgroups of diabetic patients. The fibrinolytic system is probably not involved in type 1 diabetes mellitus. PMID- 1452118 TI - The role of estrogen in the TSH and prolactin responses to thyrotropin-releasing hormone in postmenopausal as compared to premenopausal women. AB - The basal and TRH (Thyrotropin-Releasing Hormone) stimulated TSH (Thyrotropin) and PRL (Prolactin) responses (incremental area; IA) to 200 micrograms TRH was studied in 13 pre- and 13 postmenopausal women of 60 years of age. Both groups consisted of healthy women, none had goiter and all were negative for thyroid autoantibodies. The serum levels of TSH, T3, T4 and SHBG (sex hormone-binding globuline) were in the normal range and did not differ significantly between the groups. There were no differences in basal TSH (1.3 +/- 0.5 vs 1.4 +/- 0.5 mIU/l) or PRL (6.4 +/- 2.7 vs 6.6 +/- 2.5 micrograms/l) or for PRL IA (498 +/- 126 vs 584 +/- 165) between pre- and postmenopausal women. However, for TSH IA there was a slight decrease (15%), but not significant, in the postmenopausal group compared to the premenopausal group (1630 +/- 598 vs 2067 +/- 893). In conclusion, a weak but not significant decrease in the TSH response to TRH in postmenopausal women may be explained by the lower endogenous estradiol level. PMID- 1452119 TI - The origin of oestrone sulphate in normal and malignant breast tissues in postmenopausal women. AB - Conversion of oestrone sulphate to oestrone has been suggested to make a major contribution to the level of oestrone found in breast tissues. In order to examine the ability of breast tissues to take up oestrone sulphate (E1S), 3H E1S or E1-35S was infused into postmenopausal women with advanced breast cancer. For 3 subjects infusion of 3H E1S was repeated after treatment with Danazol, a potential inhibitor of oestrone sulphatase activity. After infusion of 3H E1S significant levels of 3H E1S were detected in normal and malignant breast tissues (tissue: plasma ratios 0.14 +/- 0.13 and 0.24 +/- 0.12 respectively, mean +/- S.D., n = 5). Similar 3H E1S tissue: plasma ratios were detected after infusions of 3H E1 indicating that the 3H E1S detected in breast tissues after infusion of 3H E1S may have originated from the hydrolysis of 3H E1S in tissues other than the breast, with subsequent uptake and sulphation in breast tissues. After infusion of E1-35S no significant levels of radioactivity were detectable in normal or malignant breast tissues. Treatment with Danazol had no significant effect on tissue levels of 3H E1S or on the CRE1S E1 or MCR-E1S. It is concluded that oestrone sulphate, as such, is not taken up by breast tissues and that any contribution that oestrone sulphate makes to the oestrogen content of breast tissues will depend upon prior hydrolysis. PMID- 1452120 TI - Does glucagon preserve its insulinogenic effect during tolbutamide-induced hypoglycemia? PMID- 1452121 TI - Effect of muscle constriction on 3-hydroxybutyrate uptake using the microdialysis technique. PMID- 1452122 TI - Pathomorphological findings in thyroid cancers of children from the Republic of Belarus: a study of 86 cases occurring between 1986 ('post-Chernobyl') and 1991. AB - Recently, an impressive increase in malignant thyroid tumours has been observed among children less than 15 years of age living in the Republic of Belarus at the time of the nuclear accident of Chernobyl in 1986. More than half of these patients lived in the region of Gomel, nearest to Chernobyl. Because of the very short time interval between the accident and the tumour occurrence an independent review of the available histopathological material was done. Out of 101 cases diagnosed as thyroid cancers, we reviewed slides of 93 cases and agreed the diagnosis of malignancy in 92.5%. Of these tumours 96.5% were papillary carcinomas, 61.5% were moderately or poorly differentiated. Extrathyroidal extension was observed in 60.5%, regional lymph node metastases in 74% and distant metastases in 7%. One of the patients died from lung metastases. Our results confirm that the neoplasms increasingly diagnosed between 1986 and 1991 among children of this region are thyroid carcinomas. In addition, we correlate several histopathological findings with sex and age of the patients and other parameters, and compare the results with data from other studies. PMID- 1452123 TI - Histological examination of first trimester spontaneous abortions: the impact of materno-embryonic interface features. AB - Cytogenetic findings and placental histological features of 319 consecutive first trimester spontaneous abortions were retrospectively investigated. Correlation of cell culture results and microscopic examination based on conventional villous histological criteria showed an overall sensitivity of 45.1% for histology in detecting chromosomal anomalies. Discrepant cases, i.e. normal histology with unequivocal chromosomal anomaly and abnormal histological features suggesting a chromosomal anomaly according to the classical criteria but with a normal karyotype, were reviewed by two independent observers using extended histological criteria including features of the materno-embryonic interface. There was a significant (P < 0.001) increase of the sensitivity of histology to 66.4% for both observers after the second histological examination. Macerated specimens or incomplete specimens made of chorion laeve or maternal decidua only are difficult to evaluate, and represent the main cause of discrepancy between cytogenetics and morphology. The results of this study indicate that the sensitivity and specificity of microscopic examination in cases of early spontaneous abortion may be improved by adding features of the materno-embryonic interface to classical villous histological criteria. PMID- 1452124 TI - The lymphoepithelial lesion of gastric low-grade B-cell lymphoma of mucosa associated lymphoid tissue (MALT): an ultrastructural study. AB - Lymphoepithelial lesions are a characteristic feature of primary, gastric low grade lymphomas of mucosa-associated lymphoid tissue (MALT). The lymphoepithelial lesions in 12 such lymphomas have been examined by electronmicroscopy and immunohistochemistry. The lymphocytes present in these lesions are neoplastic centrocyte-like (CCL) B-cells and are morphologically and immunophenotypically similar to those of the surrounding lymphoma. Once the CCL cells penetrate the gastric glands, there is marked structural distortion and disruption of the epithelial cells which leads to their ultimate death. The close association of the neoplastic CCL cells and epithelial cells suggests the presence of a factor, an antigen or other receptor, on the plasma membrane of the latter through which these effects are mediated. PMID- 1452125 TI - The peritubular myoid cells in the testes from men with varicocele: an ultrastructural, immunohistochemical and quantitative study. AB - Ultrastructural and some immunophenotypic features of the peritubular myoid cells of testes from normal men and from men with varicocele were studied. The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In normal testes only type a and b tubules were found, whereas the testes from men with varicocele showed type b-e tubules. Myoid cells in tubule types a and b showed slender cytoplasmic projections with abundant, parallel arranged microfilament bundles and electron-dense bodies. In c tubules, the myoid cells showed the same ultrastructure. The myoid cells of tubules with advanced (type d) or complete (type e) sclerosis showed irregularly outlined nuclei, scant microfilament bundles and absence of electron-dense bodies. Immunostaining of myoid cells with anti-actin antibodies was intense in types a-c tubules and scant in types d and e. Immunostaining with anti-desmin antibodies was intense in tubules types a-d, but the immunoreactive cells in types c and d tubules were irregularly shaped and distributed and were scanty in tubule type e. Immunostaining with anti-vimentin antibodies was weak in types a-c tubules and intense in types d and e tubules. Quantitative studies revealed that, with the progression of sclerosis, the numbers of both actin- and desmin-immunoreactive cells per cross-sectioned tubule, and the surface area occupied by the immunostained portion of these cells, decreases while the number of vimentin immunoreactive cells and their immunostained surface area increases. PMID- 1452126 TI - Cribriform intra-tubular epididymal change and adenomatous hyperplasia of the rete testis--a consequence of testicular atrophy? AB - We have observed an unusual change in the epididymal tubules, ranging from focal epithelial proliferation forming bridges, to a pronounced intra-tubular cribriform pattern of the epithelium. This often occurs in association with adenomatous hyperplasia of the rete testis which is an uncommon, usually incidental finding. Both processes appear associated with underlying testicular atrophy and may be related to local hormonal imbalance. PMID- 1452127 TI - Lymph node findings in generalized mastocytosis. AB - Lymph nodes from 21 cases of generalized mastocytosis were studied histologically to confirm or exclude mast cell infiltration, and to investigate their micro architecture. Mast cell infiltrates were detected in 17 (80%) of the lymph nodes and were found mainly in the medullary cords and sinuses. Diffuse infiltration was seen in 14 cases and focal infiltration in three cases. The following pathological findings were frequently observed: germinal centre hyperplasia (n = 14), which is probably a nonspecific finding; and hyperplasia of small blood vessels, which sometimes resembled high endothelial venules (14), eosinophilia (8), plasmacytosis (7) and collagen fibrosis (6), all of which may well be related to the effects of mediators released by mast cells. Infiltrates of acute or chronic myeloid leukaemia were seen in six lymph nodes. Division of the cases into two prognostically different groups, i.e. systemic mastocytosis, in which the skin lesions of urticaria pigmentosa are present and the prognosis is favourable, and malignant mastocytosis, in which there is no cutaneous involvement and the prognosis is poor, revealed that all six lymph nodes exhibiting leukaemic infiltrates came from the malignant mastocytosis group; eosinophilia, plasmacytosis and fibrosis were seen significantly more often in malignant than in systemic mastocytosis, but blood vessel hyperplasia and germinal centre hyperplasia were encountered with the same high frequency in both groups; and mast cell atypia tended to be more pronounced in malignant mastocytosis; this diagnosis could therefore easily be missed without naphthol AS D chloroacetate esterase staining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452128 TI - Benign epithelial neoplasms of the appendix: classification and clinical associations. AB - The nomenclature of non-carcinoid epithelial proliferations of the appendix is confused and many of the terms used have no histogenetic basis. A classification based on the well-established diagnostic categories of colonic epithelial polyps has been proposed recently. We have applied this classification to 42 benign epithelial lesions of the appendix in order to determine its suitability for routine diagnostic use, and in order to determine the prognosis of patients with these lesions. All lesions could be classified as either hyperplastic, adenomatous, mixed hyperplastic/adenomatous or dilated appendices. Six cases were associated with a synchronous carcinoma of the colon with all types of appendiceal histology being represented. Follow-up of the remainder of the patients revealed two subsequent colonic carcinomas, at 3 and 6 years post appendicectomy respectively. In both of these patients, the appendix had shown adenomatous epithelium. We suggest that adenomas of the appendix may have a similar prognostic significance to adenomas elsewhere in the large bowel. PMID- 1452129 TI - Immunohistochemical localization of basement membrane type VII collagen and laminin in neoplasms of the head and neck. AB - The distribution pattern of the basement membrane components type VII collagen and laminin, was studied immunohistochemically in normal human head and neck tissues and in a series of benign and malignant tumours from the same site. Using monoclonal antibodies, a basement membrane containing type VII collagen and laminin could be demonstrated beneath the epithelial cell layer in 16 normal head and neck tissues from different localizations. Unlike type VII collagen, laminin was also abundantly present around blood vessels and muscle fibres. With respect to 42 squamous cell carcinomas studied, type VII collagen and laminin were present in basement membranes surrounding small and large tumour fields, independent of the tumour grade. Type VII collagen was demonstrated in the cytoplasm of tumour cells in 36% of the cases, while the antibody to laminin displayed a basement membrane staining pattern mainly. Both antibodies showed a staining gradient in more than half of the cases, with strong staining in the centre of the tumour and weakening of the staining towards the tumour periphery. In a series of 22 salivary gland tumours consisting of 19 pleomorphic adenomas and three adenoid cystic carcinomas, the distribution pattern of type VII collagen and laminin was very heterogeneous. Laminin was present in 17 and type VII collagen in 10 of 19 cases of pleomorphic adenoma, mostly scattered throughout the tumour fields. In the tumours positive for type VII collagen areas with little or no positivity were also found. A correlation between type VII collagen positivity and the presence of basal cell keratin 14 positivity was noticed in the majority of cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452130 TI - C-cell hyperplasia in secondary hyperparathyroidism. AB - Calcitonin is a hypocalcaemia producing hormone and is secreted by C-cells of the thyroid. The current study was undertaken on a hypothesis that C-cell hyperplasia may develop in the secondary hyperparathyroidism of chronic renal failure in response to sustained hypercalcaemia. With an immunoperoxidase staining method for calcitonin, C-cell hyperplasia was noted in four of six cases of autosomal dominant polycystic kidney disease and in three of six cases of acquired renal cystic disease, an overall incidence of 58% compared with an incidence of 36% (five of 14) in cases of primary hyperparathyroidism with parathyroid adenoma. Thus, both primary and secondary hyperparathyroidism may trigger C-cell hyperplasia in an attempt to produce a hypocalcaemic effect. PMID- 1452131 TI - Secretory meningioma. PMID- 1452132 TI - Vasculitis in ileocaecal tuberculosis: similarities to Crohn's disease. PMID- 1452133 TI - An unusual presentation of transitional cell carcinoma of the distal urethra. PMID- 1452134 TI - Lymphangioma-like change of the thyroid. PMID- 1452135 TI - Solitary microcarcinoid in ulcerative colitis. PMID- 1452136 TI - Primary Kaposi's sarcoma of intraparotid lymph node. PMID- 1452137 TI - [Composition and distribution of lipid and apolipoprotein in plasma lipoproteins of endogenous hypertriglyceridemia]. AB - Lipids and apolipoproteins in plasma VLDL, IDL, LDL, HDL2 and HDL3 isolated by one-step density gradient ultracentrifugation from 7 subjects with endogenous hypertriglyceridemia (HTG) and 4 normalipemics were determined. HTG VLDL was enriched with cholesterol, and its triglyceride (TG), phospholipid (PL) and apo CII, CIII contents (mg/100 mg protein) were significantly higher than those in normal VLDL. ApoE content in HTG VLDL was prone to increasing, and apoB100 content had no apparent difference from that in normal VLDL. Compared with normal HDL2 and HDL3, the contents of total cholesterol (TC), apoAI, CII, and CIII in HTG HDL2, and apoCII, CIII in HTG HDL3 decreased. HTG HDL2 and HDL3 were rich in TG. By analysis of distribution of these lipids and apolipoproteins in various plasma lipoproteins, it was found that the abnormal composition of VLDL and HDL in HTG seemed to be a result of transport of TC, PL, and apoCII, CIII from HDL to VLDL. There was a significantly positive correlation between TC and apoAI, CII, CIII in HDL respectively, which indicated that apoCII and CIII were also associated with the alteration of HDL cholesterol. It is suggested that the elevated plasma VLDL-TG concentration in endogenous hypertriglyceridemia may induce abnormal redistribution of lipid and apolipoprotein among apoCII plasma lipoproteins, and and CIII may play an important role in these changes. PMID- 1452138 TI - [Assay of genomic DNA homology among strains of different virulent leptospira by DNA hybridization]. AB - Nick translation labelling technique was applied to the preparation of two 32P labelled genomic DNA probes from L. interrogans serovar Lai strain 017 and Leptonema illini strain 3055, respectively. Dot-blotting and Southern-blotting with DNA of five strains leptospira from different genus and species were performed. The results showed that certain differences among the L. interrogans, L. biflexa and Leptonema illini could be detected by endonuclease assay. L. interrogans strain 017 with L. biflexa strain Patoc I and Leptonema illini 3055 strain exhibited very little homology. L. interrogans strains 017, 601, and 245 from different serogroup and serovar had a high degree of homology. Leptonema illini strain 3055 showed little homology with L. interrogans and L. biflexa. Therefore DNA hybridization may be used as a tool for the identification and classification of leptospira. PMID- 1452139 TI - [Investigation of microbicidal activity of neutrophil defensins against leptospires]. AB - Defensins play an important role in oxygen-independent microbicidal mechanisms of neutrophils. They are effective against many bacteria, fungi and enveloped viruses. However, the effect of defensins upon leptospires has not been studied. In the present report, human defensins (i.e. HNP, a mixture of HNP1, HNP2 and HNP3 were prepared from human polymorphonuclear neutrophils by chromatography on Sephadex G-100 and then on Biogel P-10. Rabbit defensin NP1 was purified from rabbit peritoneal granulocytes by preparative acid urea polyacrylamide gel electrophoresis. By using the most-probable-number procedure, HNP and NP1 were tested in vitro for the killing of leptospira interrogans serogroup icteroheamorrhagiae serovar lai strain 017. NP1 was highly effective. When leptospires of strain 017 were incubated with 1 microgram/ml of NP1 at 30 degrees C for 4 hours, > 99% of these organisms were killed. HNP was less potent than NP1, and at 50 micrograms/ml, it killed > 90% of leptospires. As is also the case for the killing of bacteria, NP1 was active against leptospires in nutrient-free buffer, whereas HNP required the addition of glucose. The data suggest that defensins could play a major role in the killing of leptospires by neutrophils. PMID- 1452140 TI - [Detection of leptospira by dot blot hybridization with photobiotin- and 32P labelled DNA]. AB - Photobiotin- and 32P-labelled DNA probes of L. interrogans sv. lai strain 017 were produced and the DNA and leptospires were dotted on the NC filter and hybridized. The results showed that photobiotin and 32P-labelled DNA probes could detect DNAs of homology. The smallest amount of DNA that could be detected with the probes were 5pg and 1pg, and the smallest numbers of pathogenic leptospires were 5 x 10(3) and 10(3), respectively. Nonpathogenic leptospires. L. biflexa sv. patoc strain Patoc 1, L. illini strain 3055, Escherichia coli, Bacillus aerogenes capsulatus, and Salmonella anatis, could not be detected by the probes. The study demonstrates that leptospires DNA probe could be produced by labelling the DNA with photobiotin. It has higher sensitivity and specificity and can be used for detection of leptospires in the field and clinic. PMID- 1452141 TI - [The construction of rich genomic library of bovine Y chromosome]. AB - According to the fundamentals of DNA renatured kinetics, we made a study in which genomic DNA from male cattle was completely digested with Sau 3A, while female DNA was sheared to an average size of 500 bp fragments. The Y derived DNA sequence rich library of bovine has been contracted with pUC19 plasmid as vector and JM109 as host bacteria by reassociation of male and female DNA. Male and female DNA probes, were used. The result of colony hybridization showed that out of 1000 recombinants analysed, 6 were found to be stronger signal with male probe. Analysis of Pvu' I digested DNA fragment revealed that most of the inserts were in the 90-300 bp. PMID- 1452142 TI - [Thixotropic properties of whole blood in children with congenital heart disease]. AB - The thixotropic parameters of whole blood in two groups of children with congenital heart disease (CHD) were measured. Group 1. cyanotic heart disease (CCHD), 20 cases; Group 2. acyanotic heart disease (ACHD), 30 cases. Fifty healthy children were controls matched with the patients in sex and age. Their thixotropic parameters were compared; the paired t-test was used. In the children with CCHD, the hematocrit (HCT), the yield stress (tau 0) the Newtonian contribution of viscosity (mu), the equilibrium value of the structural parameter (A), the apparent viscosity at 2.37 sec-1 (eta s) and the Non-Newtonian contribution of viscosity (eta s-mu) were significantly higher than those in corresponding control groups. In the children with ACHD, only the values of tau 0, eta s-mu, and eta s were higher than those in control groups. All of the thixotropic parameters in CCHD group were significantly higher than those in ACHD group. Thus we described quantitatively CHD in terms of thixotropy of blood. The thixotropic parameters of blood could be used as indexes of severity for pathologic changes of CHD. PMID- 1452143 TI - [Noradrenaline fluorescence histochemical study on the locus coeruleus of kindling rat induced by coriaria lactone]. AB - Fourteen male Wistar rats were divided into two groups. The experimental rats were injected with subconvulsive dosage of coriaria lactone (1 mg/kg) intramuscularly per 3.5 days. The controls were injected with normal saline. After 26 injections, the loci coeruleus of kindling rats were studied with the noradrenaline (NA) fluorescence histochemical technique at the time between seizures. The NA fluorescence could be clearly visualized under fluorescent microscope. The intensity of fluorescence was reflected by autoexposure-meter of the fluorescent microscope. The brighter the fluorescence, the shorter the autoexposure time. The intensity of NA fluorescence in the locus coeruleus of experimental animals was weaker than that of the controls. Since NA plays an inhibitory role in cerebral cortex, the decrease of NA, either induced by repeated injections of coriaria lactone or due to the time of sample taken after seizure, needs further study. PMID- 1452144 TI - [Histochemical and image-analytic study of the rat locus coeruleus during status epilepticus]. AB - Twenty-four adult male Wistar rats were used in this study. Status epilepticus was provoked in 10 rats by embedding coriaria lactone particle into the left cerebral motor cortex. In the controls were embedded particles without coriaria lactone. After 6 h of continuous seizure, the locus coeruleus was studied with the noradrenaline (NA) fluorescence histochemical technique and enzyme histochemical test for monoamine oxidase (MAO). The intensity of NA fluorescence was detected with fluorescent microscope autoexposuremeter and analysed with MIAS 200 Image Analyser. The study group showed a parallel increase of NA fluorescence as compared with that of the control group by both measurements. NA plays an inhibitory role in the cortex. Our data suggest that the increase of NA in locus coeruleus may be due to the reduction of NA release from axon terminal. Reduction in inhibition could be one of the mechanisms of seizure activity. The intensity of MAO was detected with MIAS-200 Image Analyser. The regulation of monoamine metabolism by MAO in the central nervous system and the increase of MAO activity in the continuous seizure group may be induced by the accumulation of NA in the locus coeruleus soma. PMID- 1452145 TI - [Ultrastructural observation of SC1001-sodium on brain neurons kindled seizures by coriaria lactone in rabbits]. AB - The ultrastructural changes of hippocampus and cerebral cortex neurons were derived from the rabbits kindled by coriaria lactone and from the kindled rabbits after treatment with SC1001 Na. The results of experiment showed that the hippocampus and cerebral cortex neurons in the kindled group had some degenerative changes, such as the swelling mitochondria, dilated rough endoplasmic reticulum and Golgi complexes when the injuries of neurons were not serious, but the seriously injured neurons were subjected to rupture of the cell membrane and solution of most organella, with only a small amount of degenerative organella. In the group treated with SC1001 Na, the ultrastructure of brain neurons demonstrated a tendency of recreation to normal which showed that SC1001 Na had cured many of the degenerative brain cells. This suggested that active treatment is very important for the epileptic patients. PMID- 1452146 TI - [The purification and properties of LD5 from normal C57 mouse liver, H22 hepatoma and S180 sarcoma]. AB - Type-A LDH (LD5), isolated from normal C57 mouse liver, H22 hepatoma and S180 sarcoma after a sequential ion-exchange and affinity chromatography, was examined to be quite pure. Studies on the enzyme kinetics and immunological properties showed that there were no differences in optimal pH, optimal temperature, subunit MW., isoelectric point between normal and malignant (H22 hepatoma and S180 sarcoma) LD5. Km to pyruvate decreased in malignant LD5 while LD5 content and percentage increased. Three LD5 antibodies raised against rabbits showed cross reaction. These antibodies as probes are useful in the isolation of LD5-mRNAs from G57 mouse liver H22 hepatoma and S180 sarcoma. PMID- 1452147 TI - [Isolation and identification of a strain of Pseudomonas SP. producing insoluble glucan hydrolase]. AB - A strain, CIB871, isolated from the natural world can hydrolyze insoluble glucan(IG) produced by S. mutans. This organism has been identified to be a strain of Pseudomonas SP. It grows well at 30 degrees C. The optimum medium for producing insoluble glucan hydrolase (IGase) is composed of 0.3% peptone, 0.03% IG and M1 salt solution (NH4)2 SO4 1mg/ml, MgSO4 50 micrograms/ml, FeCl2 50 micrograms/ml, K2HPO4 0.5mg/ml). The IGase production reached maximum when cultured for 65-70 hours. PMID- 1452148 TI - [Age-related change of synaptic number in the suprachiasmatic nucleus of the rat hypothalamus]. AB - Numerical changes of the synapses in the hypothalamic suprachiasmatic nuclei (SCN) of rats at different ages were investigated with electron microscope, The population of the major SCN synapses formed with dendrite and total number of synapses were found to be reduced with advancing age. Compared with the young animal group, the synaptic number was statistically different from that in the adult or senescent group. As a result of these changes, the function of SCN might decline with aging. PMID- 1452149 TI - [Effects of insulin on expression of oncogenes in CWE mouse brain]. AB - By RNA dot blot hybridization, we observed the expression of c-myc, c-fos, Ha-ras and erbB genes in normal brain of CWE mouse after the injection of insulin. Transcription of the c-myc and c-fos genes is greatly increased, which peaks approximately 2 h after insulin stimulation, decreases in 6 h and returns to the initial levels within 48 h. The alteration in Ha-ras transcription appears more complex; its expression decreases first but increases subsequently. We also detected the expression of erbB gene which decreases after the injection of insulin. The results suggest that c-myc, c-fos, Ha-ras and erbB might be directly involved in growth control. Their protein products might play a role in intracellular signal transduction. PMID- 1452150 TI - [Comparative study on activity of adenylate cyclase in normal human ovary with ovarian tumors]. AB - It has been documented that the binding activity sites of human chorionic gonadotropin (HCG) receptor and kd in human ovarian tumors are different from those in the normal ovary. And some observations suggest that the HCG receptor depends on adenylate cyclase (AC) for its physiological functions. We studied the activity of AC in normal human ovary and ovarian tumors. Five human ovarian specimens and eighteen ovarian tumor specimens were obtained from women patients undergoing gynecological surgery. Ovaries were homogenized and sonicated. The homogenates were centrifuged at 1000 x g for 15 min. After sucrose density gradient ultracentrifugation (78000 x g, 4 h), the membrane fraction was collected from interface between 33% and 37%. The membrane protein approximately 10 micrograms, ATP 1 mmol/L, 3H-ATP 5 x 10(4) cpm, sulphydryl-ethyl alcohol 10 mmol/L, in a final volume of 200 microliters of Tris-HCl buffer (50 mmol/L), pH7.5, containing MgSO4 5 mmol/L, were incubated at 35 degrees C for 10 min. The reaction was stopped by boiling water bath for 3 min. The AC activity (U/mg): of human normal ovary, 67 +/- 8, of cystadenocarcinoma serous, 146 +/- 70; of cystadenocarcinoma mucinous, 289 +/- 83. PMID- 1452151 TI - [Two pairs of particular structures of mandibular joints of mammalian sorex]. AB - The mandibular joints of Chinese Anouroserex squamipes, spuamipes, MILNE-EDWARDS were examined by gross and microscopic studies. We discovered that there were two pairs of joints in these animals. The upper pair of joints, named lateral mandibular joints, were placed on both sides under the parietal bone. The lower pair of joints, named skull-base mandibular joints, were placed on both sides of the skull-base. These two pairs of joints could not be observed simultaneously in the same plane either sagittally or frontally. The lateral fossa and condyle were obliquely from outward, backward and upward to inward, forward and downward on both sides; the fossa looked like a groove concave downward, and the head of the condyles appeared in a cylindrical form. The lower fossae and condyles were transversely forward and inward from the lateral mandibular joints; the fossa looked like a shallow spoon concave upward, and the condyle appeared in a flat surface to fit the upward fossa. The sorex likes to dig holes on the ground to live in and search for insects in the soil to eat. The skull-base mandibular joints will support the jaw to counteract the digging force and protect the lateral mandibular joints from injury. This study has suggested that the morphology of the mandibular joints is adapted to their functional requirements during evolution. PMID- 1452152 TI - [Circadian rhythm of blood pressure in renovascular hypertensive goats treated with captopril]. AB - Blood pressure (BP) was recorded directly and automatically by a microcomputer aid system for 48 h in normotensive and Goldblatt hypertensive goats. By population-mean cosinor fitting, significant circadian rhythms were found for SBP and DBP in both groups of goats. The BP during nighttime was higher than that during daytime in our goats. An angiotensin converting enzyme inhibitor, captopril, was given to hypertensive goats with usual schedule of drug administration (25mg, t.i.d) or form of chronotherapy (62.5 mg, given before the acrophase of BP, q.n). BP significantly decreased throughout the whole day in both treated groups. But there was no statistical difference of cosinor parameters between the effects of BP in these two groups. BP could be decreased by the method of chronotherapy with less amount of drug and less frequency of drug administration. PMID- 1452154 TI - [Observation of the morphological genesis of pleural mesothelioma induced by asbestos in rats]. AB - In order to observe the lesions of pleural mesothelia caused by asbestos, we injected asbestos fiber into the pleural cavity of Wistar rats. The result showed that there Was an obvious process for the morphological genesis of mesothelioma. Simple hyperplasia and stratified pleomorphic hyperplasia of mesothelial cells were found on the 30th and 106th day after the injection of asbestos fiber, respectively. The benign and malignant mesotheliomas were noted on the 300th day. Meanwhile, a two-way differentiation may be observed in the process of mesothelial hyperplasia. PMID- 1452153 TI - [Effect of Chinese-made vesnarinone on experimental heart failure of dog]. AB - Intravenous drip of sodium pentobarbital 6 mg/kg per min induced obvious heart failure of anesthetic dogs (n = 11) followed by an infusion of 0.25 mg/kg per min to maintain the heart failure state. The Chinese-made vesnarinone 3 mg/kg was injected, followed by an infusion of 0.1 mg/kg per min, or the solvent in the same volume, for 30 min. Vesnarinone increased significantly and instantly the cardiac output and left ventricular maximum + dp/dt, which almost recovered to normal at the end of the infusion and also significantly increased 30 min after administration. The positive inotropic effect of vesnarinone was not accompanied by an increase in the heart rate and the blood pressure. The results of our experiment reveal that the Chinese-made vesnarinone has a potent and relatively selective positive action on heart failure of dogs. PMID- 1452156 TI - [The toxicity of herbicide Asulam]. AB - We conducted a series of toxicity tests and short-term mutagenic assays of Asulam and 40% (W/V) sodium Asulam. It was found that the LD50 of Asulam with acute oral toxicity was 30000 mg/kg for mice, and the LD50 of sodium Asulam for mice and rats were equal (8250 mg/kg). The cumulative coefficient of sodium Asulam in Wistar rats was 9.42. None died from sodium Asulam absorbed via skin. Negative results were obtained in Ames test, Bacillus subtilis repair test and the micronucleus test. There was no significant difference between the control group and the treated groups in the chromosomal aberration rates of spermatogonia and primary spermatocytes of mice testis. The results indicated that Asulam should be regarded as a substance of low toxicity and low accumulation. No mutagenicity was observed in our experiment. PMID- 1452157 TI - [A method of mercapto cotton/Ag-DDC determination for inorganic arsenic in seafood]. AB - A method of mercapto cotton/Ag-DDC determination for inorganic arsenic in seafood was developed. It is reliable and simple--The coefficients of variation for 1.0 5.0 micrograms As (III), kelp and dried small shrimp samples are 1.5-5.6%, 4.4% and 9.5%, respectively. The recoveries of kelp and dried small shrimp samples are 82.0-102.6% and 83.0-97.1%, respectively. As compared with the results of the extraction method (Government standard) in the determination of inorganic arsenic levels in 10 kinds of seafood, the results of this simple method showed no significant difference. PMID- 1452155 TI - [Aluminum and fluorine in blood and bone of rats fed on diet mixed with various contents of aluminum, fluoride or their mixture]. AB - Wistar rats were divided into 8 groups:control, 300 ppm F, 130 ppm F, 300 ppm Al, 1200 ppm Al, 130 ppm Al + 130 ppm F. 300 ppm Al + 300 ppm F and 1200 ppm Al + 300 ppm F. The chemicals were mixed into the standard diet. The animals were fed on the diets for 12 weeks. Contents of F, Al, Ca and P in the blood (or serum) and humerus were determined at the end of 12 weeks. The results showed that the level of F in the blood and bone in the unadulterated F group was increased, especially F in the bone reached a level more than 10 times that of the control. In the 3 mixture groups, blood F and bone F were lowered, while blood F was restored to normal level, but bone F was not nevertheless, the results showed that Al was in antagonism to the absorption of F. In the unadulterated Al groups, blood and bone Al did not parallel with the amount of Al administered. The level of Al in the median Al group was higher than that of the high Al group. Taking the level of blood and bone Al as a measure, when different doses of Al were administered with F, in the low and median dosage of Al, F was in antagonism to Al absorption, but in case of high dosage of Al, F was in potentiation to Al absorption. In all the experimental groups serum P was elevated, but serum Ca was not disturbed. Bone Ca and P were decreased only in the 3 groups with unadulterated F as well as unadulterated and adulterated high dosage of Al. Mechanism of the nonlinearity of Al absorption vs Al dosage, as well as the dual effect of F on the absorption of Al was proposed. PMID- 1452159 TI - [A study on the pathogenicity of Helicobacter pylori in chronic gastritis and peptic ulcer disease]. AB - Gastroendoscopic biopsy specimens from 366 patients were stained with HE, Warthin Starrys or Giemsa and mucin histochemical methods. Positive rate of Helicobacter pylori (HP) was 73.8% in chronic gastritis. Positive rates of HP in gastric ulcer disease were 88.2%, 91.9%, and 11.1% at the near and distant mucosa of ulcer and in duodenitis, respectively. Positive rates of HP in duodenal ulcer disease were 81.5%, 24.6% and 7.2% at the pyloric-antral area and at the near and distant mucosa of duodenal ulcer, respectively. The number of HP in active inflammation was higher than that in inactive inflammation (P < 0.05). The HP almost lived in the neutral mucin. There was no statistical significant difference between near and distant mucosa of ulcer (P > 0.05). HP might play an important role in the pathogenesis of chronic gastritis, and it might aggravate the peptic ulcer disease. PMID- 1452158 TI - [Determination of bendazac lysine by RP-HPLC]. AB - Bendazac (BD) was separated on a CLC-ODS column, 150 x 6 mm id (Shimadzu), using methanol acetic acid 0.1 mol/L (67:33) as the mobile phase. The flow rate was 1.0 ml/min and the detection wavelength, 254 nm. The detection limit of BD was 0.1 ng (R/N, 3:1), which was determined by the peak area measurement using an external standard method. The calibration curve was linear in the range of 5-10 micrograms (r = 0. 9998). The average recovery of BDL was 99.46 +/- 0.59% (n = 9). This method has been applied satisfactorily to the determination of BDL samples. PMID- 1452160 TI - [Alveolar soft part sarcoma: a clinicopathologic and immunohistochemical study of 13 cases]. AB - Thirteen cases of alveolar soft part sarcoma were studied clinicopathologically and by the PAP technique antisera against desmin, myoglobin, S-100 protein, neuron-specific enolase (NSE). We suggested, light microscopically, the main points for diagnosis and differential diagnosis of alveolar soft part sarcoma. Immunohistochemically, the tumor cells reacted positively for desmin (five cases), myoglobin (three cases) and NSE (four cases). No immunoreactivity for S 100 protein was observed. Similar results had been reported by others. No definite conclusion about histogenesis of alveolar soft part sarcoma could be drawn from the small number of cases in this study. PMID- 1452161 TI - [Hepatic segmentectomy using microwave tissue coagulator]. AB - Hepatic segmentectomy using a microwave tissue coagulator guided by intraoperative ultrasonography is a new operative procedure, which our research unit was the first to start using from 1990. Up to now we have performed this kind of operation with success in 26 cases. Our results suggested that the new procedure simplified the original operation and greatly reduced the risk of hemorrhage and iatrogenic spread of the cancer cells during operation. Besides, this operation as a kind of definite anatomic hepatectomy can minimally resect the tumor bearing tissue in a radical fashion, while maximally preserve the tumor free tissue of the liver. PMID- 1452162 TI - [Measurement of T-lymphocyte subsets in bronchial alveolar lavage fluid on smokers and patients with lung cancer]. AB - The measurements of T-lymphocyte subsets (as expressed by, CD3 CD4 and CD8) in the peripheral blood and bronchial alveolar lavage fluid (BALF) on 30 cases of lung cancer, 26 cases of smoker and 25 cases of nonsmoker have been done. The results showed that there existed no differences in the peripheral blood of the above said subsets of lymphocyte. In BALF the percentage of CD3 in all the lymphocytes did not show any significant difference among the three tested groups, either (P > 0.05). But the percentage of CD4 and the ratio of CD4/CD8 manifested the following peculiarity: patients with lung cancers < smokers < nonsmokers (P < 0.01). On the contrary, the percentage of CD8 showed just the opposite: patients with lung cancer > smokers nonsmokers (P < 0.01). It was suggested that the cellular immunity as shown in the peripheral blood did not correspond with the findings in the BALF. The cellular immunity of the lungs was decreased both in patients with lung cancer and smokers, but more severely in the group of lung cancer patients. Smokers who have had changes of above said subsets of lymphocytes in the lungs may develop lung cancer. As the lung cancer advances, it may suppress body immunity and in turn enhance the cancer growth. Both the cause and the effect are interrelated. Therefore, the provocative agents for cellular immunity may act as one of the adjunctive therapies for patients with lung cancer. Giving up smoking should play an important role in recovering or promoting the immunity of the lungs and decreasing the incidence as well as improving the prognosis in patients with lung cancer. PMID- 1452163 TI - [Cost-effectiveness analysis of short-term course and regular course of antithyroid drug therapy for Graves' disease]. AB - One hundred and- eighteen newly diagnosed patients with Graves' disease were treated by tapazole for 6 months (short-term course) and followed up for another 12 months. Forty three percent remission rate was found in this group. A regular course of antithyroid drug therapy for 1.5-2 years with 50% remission rate was taken as control. Cost-effectiveness analysis was made to compare the cost in the two different kinds of therapy. The results showed that the total costs of the treatment per 100 cases were 17,746 yuan for the short-term therapy and 30,708 yuan for the regular therapy, with an average of 412.7 yuan and 614.2 yuan per case respectively. In comparison with the short-term therapy, the regular course could remit 7 more cases at a cost of 12,962.40 yuan, with an average of 1851.80 yuan per case. Therefore, the cost was high by prolonged course of therapy to increase slightly remission rate, although it could remit a few more cases. This study suggests that six-month treatment is preferable for those who live in the rural or remote area where the economy was less developed. A longer course of therapy may be unnecessary for those who have been treated by antithyroid drugs for 6 months or longer and are predicted to obtain a possible prolonged remission. PMID- 1452164 TI - [Female pseudohermaphroditism with a phallic urethra--a case report]. AB - Female pseudohermaphroditism with penile urethra caused by virilizing adrenal tumor in the mother is rare. A case is reported in this article. After operation the diagnosis was verified pathologically. Exposure of a female fetus to endogenous or exogenous androgens before the seventh or eighth week of fetal age may result in male external genitalia. It is emphasized that any cryptorchid phenotypic male born to a virilized mother should be proved by sex chromatin and sex chromosomes to exclude pseudohermaphroditism and that in any case of unexplained female pseudohermaphroditism one should explore the possibility of a maternal virilizing tumor. PMID- 1452165 TI - [Metastatic tumor of posterior fossa]. AB - Twenty-seven cases of metastatic tumor of posterior fossa were presented in this paper. Of the patients, 20 were males and 7 females; their age ranged from 20 to 68, and 89% of them were over 40 years of age. The primary foci found were bronchopulmonary carcinomas (7 cases), rhinopharyngeal carcinomas (3 cases), and cancer of the liver (1 case), but in 16 cases the primary foci were not found. All of these patients presented symptoms and signs of obviously increased intracranial pressure, and most of them had the signs of cerebellar and cranial nerves' lesions. Ventriculorgraphy and brain CT scanning were important procedures in the diagnosis, and MRI was most valuable in establishing the diagnosis and localization of posterior fossa metastatic tumors. Twenty-six patients underwent operation. The short-term follow-up study showed an improvement in 25 cases. There was one death. The surgical treatment of posterior fossa metastatic tumor was emphasized. Radiotherapy and chemotherapy were discussed. PMID- 1452166 TI - [Reduction mammaplasty]. AB - Twenty-eight breasts of 15 patients with macromastia underwent reduction mammaplasty from 1982 to 1989. We followed up these patients postoperatively for 6 months to 7 years. The follow-up time for 8 patients was over 1 year, and 4 patients over 5 years. And 3 patients labored and lactated. These 15 patients were satisfied with this operative results. The operative technology was based on Pitange's method. This method improved the site of the nipple, transposition of nipple-areola complex, and design of dermal pedicle, so that it had better effects in the breast shape, breast fixation and incision scar concealed. We suggest that the purpose of macromastia treated in reducing volume, improving breast shape, preserving lactating function. This paper also discusses the methods for nipple site, nipple-areola complex transposition, breast resection and mastopexy. PMID- 1452167 TI - Origin of changes in the epigastric impedance signal as determined by a three dimensional model. AB - The impedance technique can be used for the noninvasive monitoring of the stomach, with the epigastric impedance signal being a function of the position and configuration of the electrodes. The changes observed could be due to meal resistivity, meal volume and contractions of the gastric smooth muscles. The effect of these various factors on the epigastric impedance signal was determined for several electrode configurations using a three-dimensional model of the abdomen. When the voltage sensing electrodes are located close to the current electrodes, the signal varies linearly with meal volume. The relationship between meal resistivity and the epigastric impedance signal is nonlinear. The impedance signal varies linearly with the contractions of the circular smooth muscles of the stomach. PMID- 1452168 TI - Calculation of Doppler spectral power density functions. AB - A volume integral method for the calculation of Doppler ultrasound spectral power density (spd) functions is described. Axisymmetric flow in a circular tube with a power law velocity profile is assumed. The spd function is regarded as a probability density function for scatterer velocity, and the assumptions under which this is justified are considered. It is shown that the spd function is independent of Doppler angle except in the presence of wall reflection effects. A coordinate system centered on the beam is used and this enables the integrals to be easily formulated for arbitrary beams. Irregularly shaped and nonuniform beams can be treated. For the common flow and beam patterns, which exhibit symmetry, the volume integrals can often be reduced to a single integral and evaluated directly. The method is applied and the spectra are calculated for various different cases. Results are obtained for uniform rectangular and circular insonating beams, and for nonuniform beams with Gaussian, jinc, and sinc profiles. The effects of narrow beams and wall reflection are shown. The method may be readily applied to other beam and flow patterns, and extension to more complicated situations is also discussed. PMID- 1452169 TI - Adaptive filter for event-related bioelectric signals using an impulse correlated reference input: comparison with signal averaging techniques. AB - Many bioelectric signals result from the electrical response of physiological systems to an impulse that can be internal (ECG signals) or external (evoked potentials). In this paper an adaptive impulse correlated filter (AICF) for event related signals that are time-locked to a stimulus is presented. This filter estimates the deterministic component of the signal and removes the noise uncorrelated with the stimulus, even if this noise is colored, as in the case of evoked potentials. The filter needs two inputs: the signal (primary input) and an impulse correlated with the deterministic component (reference input). We use the LMS algorithm to adjust the weights in the adaptive process. First, we show that the AICF is equivalent to exponentially weighted averaging (EWA) when using the LMS algorithm. A quantitative analysis of the signal-to-noise ratio improvement, convergence, and misadjustment error is presented. A comparison of the AICF with ensemble averaging (EA) and moving window averaging (MWA) techniques is also presented. The adaptive filter is applied to real high-resolution ECG signals and time-varying somatosensory evoked potentials. PMID- 1452170 TI - A comparative study of simultaneous vibromyography and electromyography with active human quadriceps. AB - Vibromyographic (VMG) signals, which are low-frequency vibration signals generated during muscle contraction, were studied in comparison with electromyographic (EMG) signals recorded simultaneously during isometric contraction of the human quadriceps muscles. The comparison was accomplished by evaluating the averaged root mean squared (rms) value, mean frequency (MF), and peak frequency (PF) of the VMG and EMG signals for four muscle contraction levels at joint angles of 30 degrees, 60 degrees, and 90 degrees. The four contraction levels, namely 20, 40, 60, and 80% of maximum voluntary contraction (MVC), were estimated and controlled by the torque readings of a Cybex II dynamometer. It was found that the VMG and EMG under the same conditions on the same muscle group are in general equally sensitive to the levels of muscle contraction. Results show that the rms value of the VMG signal increases linearly, in a manner similar to the EMG rms/%MVC relationship, with increasing muscle contraction levels. Furthermore, the study indicates that the averaged MF (6-24 Hz) and PF (9-19 Hz) of the VMG signals are much lower than the MF (75-109 Hz) and PF (40-80 Hz) of the EMG signals. The slopes of MF/%MVC curves for the VMG and EMG are approximately the same for 60 degrees and 90 degrees joint angles (approximately 3.1 Hz per 20% MVC for VMG and approximately 2.6 Hz per 20% MVC for EMG).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452171 TI - Phase delay of pulmonary acoustic transmission from trachea to chest wall. AB - The frequency-dependent propagation time, or phase delay tau (f), of sonic noise transmission from the trachea to the chest wall was estimated over the 100-600 Hz frequency range using a phase estimation technique from measurements performed on eight healthy subjects. Since tau (f) can be greater than one period of the input signal at frequencies greater than 100 Hz, the unambiguous phase estimate at 100 Hz was used as a starting-point to determine the phase angle H(f) and tau (f) at higher frequencies under the constraint that the spectra did not exhibit large point-to-point discontinuities. The resulting tau (f) range of 0.9-4.1 ms is consistent with sound propagation to the chest wall through both airways and surrounding parenchyma. The frequency and spatial dependence of tau (f) indicates that with increasing frequency more sonic energy travels further into the branching airway structure before coupling into the parenchyma. These results suggest that information concerning distinct regional lung structures may be obtained by probing the system acoustically over selected frequency bands. PMID- 1452172 TI - Fuzzy control of mean arterial pressure in postsurgical patients with sodium nitroprusside infusion. AB - We developed a fuzzy control system to provide closed-loop control of mean arterial pressure (MAP) in postsurgical patients in a cardiac surgical intensive care unit setting by regulating sodium nitroprusside (SNP) infusion. The fuzzy controller, originally expert-system-based, was analytically converted to ten nonfuzzy control algorithms, which reduced execution time dramatically. The core of the control algorithms was a nonlinear proportional-integral (PI) controller whose proportional gain and integral gain adjusted continuously according to error and rate change of error of the process output. The gains became larger when process output was far from desired setpoint and smaller when process output was close to desired setpoint, resulting in more dynamic and stable control performance than the regular PI controller, especially when a linear process with time-delay or a nonlinear process was involved. The control algorithms, encoded in C programming language, were implemented to control MAP in patients. Preliminary clinical results showed that the average percentage of time in which MAP stayed between 90% and 110% of the MAP setpoint was 89.31%, with a standard deviation of 4.96%. These were calculated based on 12 patient trials, with total trial time of 95 and 13 min. PMID- 1452173 TI - Adaptive control of multiplexed closed-circuit anesthesia. AB - This paper describes the design of an adaptive closed-circuit anesthesia controller based on a multiplexed mass spectrometer system. The controller deals with measurement deterioration caused by measurement delay and rise time through a long catheter as well as long sampling times due to the multiplexed measurements. Measurement data are extrapolated between sampling periods to increase the estimation convergence rate. A multiple-step-ahead predictive control algorithm is used to calculate intermediate control inputs between sampling intervals. Simulations are used to validate the designed controller. PMID- 1452174 TI - A worst-case optimal parameter selection model of cancer chemotherapy. AB - An optimal parameter selection model of cancer chemotherapy in which two system parameters are unknown is formulated as a worst-case optimal parameter selection model. The model assumes that the unknown parameters lie within a known set. The system constraints must be satisfied over this entire set, and the objective function minimized in the worst case. The continuous dependence of the objective function and the system constraints upon the unknown parameters can be removed, making a numerical solution tractable. For the data considered it is proven that a cure is impossible no matter what the values of the unknown parameters in the parameter set. The optimal policy is shown to be relatively low dose intensity for the majority of the treatment, with the remaining drug delivered towards the end of the treatment interval. PMID- 1452175 TI - Evaluation of microwave and radio frequency catheter ablation in a myocardium equivalent phantom model. AB - A highly localized burst of energy applied to the myocardium via a transvenous catheter-mounted power source can be used to destroy endocardial tissue regions which mediate life-threatening arrhythmias. In the past, high-voltage direct current pulses, radio-frequency (RF) current, and laser light have been used as energy sources. In this paper, the use of 2450 MHz microwave energy applied via a miniature coaxial cable-mounted helical coil antenna designed specifically for this application was investigated as a means to increase the treated volume of cardiac tissue in a controllable and efficient manner during ablation. Using an array of fiber optic temperature probes implanted in a saline-perfused, tissue equivalent gel phantom model designed to simulate the myocardium during ablation, the heating pattern from the microwave antenna was characterized and compared to that induced by a commercial RF electrode catheter at 550 kHz. Effects of variable contact angle between the heat source and heart wall were assessed in terms of the radial penetration and overall volume of heated tissue. Heating patterns from the RF electrodes dropped off much more abruptly both radially and axially than the microwave antenna such that the volume of effectively heated tissue was more than ten times larger for the microwave antenna when the heat sources were well-coupled to the tissue, and more than four times larger for the microwave antenna when the sources were angled 30 degrees away from the tissue surface. PMID- 1452176 TI - Clinical application of an active electrode using an operational amplifier. AB - An active electrode (d10 mm, t6 mm) is presented, that functions as an impedance transformer (an input impedance > 10 G omega, an output impedance < 1 omega) by means of which we can derive surface EMG without any skin preparation and paste. This electrode was compared with a conventional one, and it was ascertained that the electrode could be replaced with the conventional one, and, moreover, it was preferable because it required less preparation time, and was less affected by environmental noise. PMID- 1452177 TI - Estimation of the spatio-temporal correlations of biological electrical sources from their magnetic fields. AB - Quasi-static electromagnetic systems, such as those found in biological systems, produce electric and magnetic fields whose temporal and spatial correlations reflect the source correlations in a straightforward manner. These fields can be noninvasively measured, providing information about the coherence properties of the source, which may directly represent ordered physiological processes of the organism. The description "biocoherence" will be adopted here to refer to the manifestation of the coherence in the magnetic measurements of these sources due solely to physiological processes. In this paper a general formulation linking the spatial and temporal coherence of measurable magnetic fields with the corresponding spatial and temporal coherence of the inaccessible current sources is derived in the quasi-static model. A method for reconstructing the spatial and temporal coherence of the source distribution is then presented. Such coherence maps would be useful descriptors of physiological processes occurring over time and space, and would represent more information than an image of the current sources frozen in time, or even a temporal sequence of such images. PMID- 1452178 TI - Knowing the patient: one aspect of clinical knowledge. AB - This paper analyzes the concept "knowing the patient" which was identified in a qualitative study of expert nursing practice during ventilator weaning of adult patients. The concept signified a cognitive and relational process by which the study participants determined salient aspects of a particular patient situation, while at the same time demonstrating their credibility and eliciting patient trust. The paper describes the clinical judgments, decisions, actions and patient outcomes that ensue from knowing the patient. This analysis offers a contextually specific description of nurses' clinical reasoning that illustrates a dimension of expert clinical practice from actual rather than simulated clinical content. PMID- 1452179 TI - Quality of life of hospitalized persons with AIDS. AB - This study explores quality of life from the viewpoint of Persons with AIDS (PWAs) who were interviewed during periods of hospitalization. Quality of life was viewed as the patients' perception of the relative effectiveness of a chosen or ascribed management style in solving the practical problems associated with being ill. Six management styles used by the respondents to improve their quality of life were identified. Results of this study suggest that nurses can improve PWAs' quality of life by supporting their respective management styles. PMID- 1452180 TI - Spiritual well-being, religiousness and hope among women with breast cancer. AB - The purpose of this study was to clarify spiritual health by examining the role of spiritual well-being (SWB), religiousness and hope in spiritual health. This was accomplished by obtaining questionnaire information from a convenience sample of 175 women diagnosed with breast cancer. Patients classified as intrinsically religious were found to have significantly higher scores on SWB than did those classified as extrinsically religious. There was no difference in hope scores between intrinsically religious and extrinsically religious patients, although hope was positively correlated with SWB. Existential well-being, a component of SWB, was the primary contributor of hope. The two major prognostic variables, stage of disease at diagnosis and number of positive lymph nodes, did not predict any of the scores. PMID- 1452181 TI - Exploring empathy: a conceptual fit for nursing practice? AB - After three decades, the efficacy of empathy in the clinical setting remains undocumented. Recently, concerns have been raised that the concept may be inappropriate and even harmful to the nurse-patient relationship. An analysis of the concept indicates that empathy consists of moral, emotive, cognitive and behavioral components. By tracing the integration of this concept into nursing, we suggest that empathy was uncritically adopted from psychology and is actually a poor fit for the clinical reality of nursing practice. Other communication strategies presently devalued, such as sympathy, pity, consolation, compassion and commiseration, need to be reexamined and may be more appropriate than empathy during certain phases of the illness experience. Directions for future research are suggested. PMID- 1452182 TI - A theory of care-seeking behavior. AB - Although much research has focused upon why people do and do not engage in recommended health behaviors, there is a need to develop more accurate theories to explain and predict engagement in health behaviors. Because health behaviors differ in important ways, it could be most fruitful to understand one type of health behavior, such as secondary prevention behavior. This paper proposes a theory of care-seeking behavior (CSB), based on a theory of general behavior by Triandis. Other popular theories about health behavior (i.e., Health Belief Model and Theory of Reasoned Action) also are reviewed. Empirical support for the variables identified in the theory of CSB is presented, drawing from the literature on secondary prevention for cancer. The theory of CSB is applied to the situation of seeking care for cancer symptoms. Directions for future research based upon this theory are delineated. PMID- 1452183 TI - Portrayal of nurses in advertisements in medical and nursing journals. AB - This investigation examined the content of advertisements in medical and nursing journals to determine if the images of nurses reflect the roles nurses play in health care. The method used was content analysis. Thirty-five nursing journals and 48 medical journals yielded 313 different advertisements picturing nurses. Data were analyzed using descriptive statistics, chi-square, correlation coefficients, and interpreted for overall impressions of the portrayals. Nurses are portrayed as sex objects, ornaments and as handmaidens to physicians. The findings demonstrate a freezing of the image of nurses in the print media. PMID- 1452184 TI - Attitudes of nurse managers and assistant nurse managers toward chemically impaired colleagues. AB - The purpose of this research was to determine attitudes among nurse managers and assistant nurse managers toward impaired colleagues in a descriptive correlational study method, using the Perceptions of Nursing Impairment Inventory. The study revealed no significant differences in attitudes between groups; assistant nurse managers demonstrated a more disciplinary orientation toward impairment within nursing. Both groups tended to have supportive attitudes toward impaired colleagues. Racial/ethnic origin had the most influence on nurse managers' attitudes toward chemically impaired colleagues. The Philippine/Oriental group demonstrated a stronger need to know when a colleague is impaired or receiving treatment, exhibited less belief in the treatability of impairment and displayed a stronger belief in impairment as a personality weakness. PMID- 1452185 TI - Nurses' job satisfaction: are there differences between foreign and U.S.-educated nurses? AB - This article reports the results of a job satisfaction survey administered to foreign-educated and U.S. nurses at six New York City public hospitals. Although a comparison of results for foreign-educated nurses on temporary visas (N = 322) and U.S. nurses (N = 535) revealed demographic, education and work differences, no differences in level of satisfaction were found between the two groups. Cultural and work status differences that may have affected these results are discussed. PMID- 1452186 TI - Nursing chronotherapeutics: a conceptual framework. AB - Nurses frequently make decisions about when treatments and actions are performed. The nursing concern driving this review is the timing of nursing activities to optimize desired and minimize untoward effects. A nursing conceptual framework is proposed that highlights individual and environmental factors, as they relate to rhythmic responses; as well as places within the framework for nursing actions based on customary and usual temporal patterns. PMID- 1452187 TI - Esther Lucile Brown--a memorial. AB - Esther Lucile Brown, who died in 1990 at the age of 92, was a social anthropologist at the Russell Sage Foundation for more than 30 years. Among her contributions were ground-breaking studies of the professions and stimulation of the development of medical social science. Her research on nursing stimulated professionalization and nursing education's move into the university. The accuracy of her research findings on nursing and psychosocial aspects of patient care led many to assume that she was a nurse. This memorial focuses on her contributions and personal impact on friends and colleagues. PMID- 1452188 TI - Temperament theory and research. PMID- 1452189 TI - On the dangers of invisibility. PMID- 1452190 TI - The imposter phenomenon. PMID- 1452191 TI - [New strategies in parasitological research]. PMID- 1452192 TI - [Recent findings on the pathogenicity of Entamoeba histolytica]. AB - Entamoeba histolytica is the causative agent of human amoebiasis. During recent years, research in amoebiasis has concentrated on two subjects: 1. the dual manifestation of the infection as harmless colonization of the intestinal cavity or pathogenic tissue invasion and 2. the molecular analysis of functions of E. histolytica that are considered essential for pathogenicity. Besides epidemiological studies and isoenzyme analyses, molecular genetics have revealed additional evidence that two genetically distinct forms of E. histolytica do exist, named "pathogenic" and "nonpathogenic" forms, respectively. Both can infect humans but only the "pathogenic" form is able to invade the tissue and cause disease whereas the "nonpathogenic" is not. Questions remain open about the mechanism that triggers "pathogenic" E. histolytica to become invasive and about the molecules that are involved. Current data indicate that at least three functions of the amoebae are considered essential for pathogenic tissue invasion. Pathogenicity is viewed as a result of 1. adherence of the amoeba to host cells, predominantly mediated by a galactose- and N-acetylgalactosamine-inhibitable lectin, 2. killing of host cells by a pore-forming peptide known as amoebapore, and 3. proteolysis of the host's extracellular matrix mediated by cysteine proteinases. Structural detailed molecular analysis including cloning of the corresponding genes have led to a better understanding of the function of these proteins. PMID- 1452193 TI - [New views on the pathogenesis and diagnosis of toxoplasmosis]. AB - T. gondii is one of the most occurring human pathogenic parasites in Europe. While the majority of immunocompetent individuals with T. gondii infection do not present clinical symptoms, congenital toxoplasmosis and reactivation of a latent infection in immunocompromised patients (i. e. patients with AIDS) are of high clinical relevance. A classification of T. gondii isolates is not available so far, although it was possible to demonstrate strain differences by the use of several methods, i. e. by using monoclonal antibodies. T. gondii seems to be able to infect any mammalian cell. Host cell-derived as well as parasite-derived factors seem to be important for the contact between host cell and parasite and the subsequent internalization. Following invasion, T. gondii is located within a parasitophorous vacuole that does not fuse with lysosomes. The multiplication rate of these obligately intracellular growing parasites decreases during conversion from the tachyzoite stage to the bradyzoite stage. Finally, the bradyzoites-harbouring cysts persist for the lifetime of the host. Reconversion from bradyzoites to tachyzoites may occur in immunocompromised patients. Probably, IFN-gamma is involved in this process. In addition to serological methods, direct detection of T. gondii using PCR or demonstration of circulating antigens might be routinely used as diagnostical tools in the future. Determination of specific IgA antibodies, which can be evaluated using the immunoblot technique, seem to be important for early serological diagnosis. The use of recombinant antigens might be helpful in future diagnosis to circumvent discrepancies between serological test results which could have resulted from strain-specific differences. PMID- 1452194 TI - [Malaria: immune mechanisms and immunization]. AB - In the 1990s, malaria worldwide is still the most important infectious disease. In endemic areas mostly children carry the highest burden of morbidity and mortality. Nevertheless an increasing incidence in adults can be expected. Patterns of disease and immunity within a population may be related to host parasite interactions and recent advances in immunology have contributed to a better understanding at the molecular level. Humoral and cellular responses play a major part in the immunity as well as immunopathology of malaria. Due to their extensive adaptive modulation, it will be extremely difficult to expel malaria parasites from their ecological niche. Most approaches of immunization targeted at different parasite stages, interfere with the acquisition of natural immunity and should thus be pursued with great care if implemented in the field. PMID- 1452195 TI - [The vir-regulon of Streptococcus pyogenes: coordinate expression of important virulence factors]. AB - Streptococcus pyogenes (group A streptococci; GAS) expresses important virulence factors like the antiphagocytic M protein, the complement factor-inactivating C5a peptidase and the immunoglobulin-Fc-binding proteins on its surface. The corresponding emm, scpA, and emm-related (fcrA, ennX) genes are adjacently encoded on the genome. They are coordinately in trans regulated by the positive regulatory VirR factor. The responsible virR gene is also located within this segment of the genome which was called vir-regulon. There are at least three different types of organization of the vir-regulon. A frequently encountered type is the "Large vir-regulon". It comprises from 5' to 3' the following genes: virR, fcrA, a relatively small emm, ennX, and a 4.6 kb version of scpA. Another common type is the "Small vir-regulon", which contains a virR deviating in its 3' region, a relatively large emm, and a 3.5 kb version of scpA. The "Unusual vir regulon" is less frequently detected. It closely resembles the small one, but harbors an additional 3 to 4 kb DNA fragment between emm and scpA, occasionally encoding an emm-related gene. The type of vir-regulon encoded by a GAS strain correlates to its serotype, its M class, and its expression of serum opacity factor. The structural genes of the vir-regulon are expressed at a high level during growth in exponential phase, under anaerobiosis, and at body temperature. The sensor molecule which modulates VirR activity according to these environmental conditions has not yet been detected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452196 TI - [The role of antibiotics in the management of verotoxin-associated hemolytic anemia syndromes]. AB - Significant improvements of dialysis techniques and the supportive treatment of the hemolytic uremic syndrome (HUS) during the last three decades do not veil the fact that causal therapy is not yet feasible. This holds true for the classic HUS associated with infections by verotoxin-(VT-)producing E.coli (VTEC) as for the majority of the much less frequent "atypical" forms. The influence of antimicrobial agents on production of verotoxins produced by clinical VTEC isolates was examined. Co-trimoxazole significantly increased the total yield of toxin. In contrast, ciprofloxacin, lincomycin and gentamicin caused significant reduction in toxin yields. The pathogenetic and therapeutic relevance of this finding is not yet known. Analysis of the clinical literature for the postulated relation between antibiotic treatment and development of HUS or its impact on the severity of the disease reveals a controversial picture. Based on the dynamics of the disease, the in vitro findings, and reports on unfavourable outcomes after treatment, it is concluded that antibiotics are not indicated in most cases of the enteropathic HUS or other VTEC infections. Antibiotic prophylaxis has neither been proven to be efficacious nor safe for the prevention of secondary cases during VTEC outbreaks. Apart from the implementations of hygienic measures, prospective studies on the role of antibiotics seem clearly warranted. Possible future strategies may include the design of immunological therapeutic concepts. PMID- 1452197 TI - Variants of the mucosal mast cell line (RBL-2H3) deficient in a functional membrane glycoprotein. AB - We have isolated and characterized subpopulations of the rat mucosal mast cell line, RBL-2H3, carrying either high or low density of a glycoprotein, recently established as mast cell function-associated antigen (MAFA, Ortega et al., 1991), on their surface. These populations were investigated in order to better define the involvement of the MAFA in coupling the immunological stimulation of mast cells to mediator release. The MAFA density on the cell surface of the deficient subpopulation was less than or equal to 10-20% that of the parental population and this phenotype was found to be stably maintained for several months. In contrast, the MAFA-enriched cells had maximally twice the number of copies per cell surface than that of the parental population and this phenotype was less stable. Significantly, low copy number of MAFA on the cell's surface was accompanied by a markedly different secretory response, i.e. (i) a considerable decrease in the secretory response to the Fc epsilon RI-mediated stimulus (ii) a marked enhancement of the ionomycin induced secretion. In order to gain insight into the causes for this decrease in cellular response to the Fc epsilon RI mediated stimulus, we measured the amplitudes of several biochemical processes which are assigned to the stimulus-secretion coupling cascade. The Fc epsilon RI mediated uptake of 45Ca2+ by the MAFA-deficient cells was considerably lower than that of the parental and MAFA-enriched cells. Similarly, these cell's Fc epsilon RI-induced rise in [Ca2+]i (both the initial transient as well as the sustained elevation), was markedly lower than that of the parental line and the MAFA enriched cells. Moreover, the low initial transient rise in [Ca2+]i was found to be correlated with the decrease in Fc epsilon RI-mediated IP3 levels. We therefore examined the cell's content of the phosphatidyl-inositides hydrolyzing enzyme, phospholipase C gamma 1. This was found to be similar in the parental line and in its derived subpopulations. However, PLC gamma 1 activation, as measured by the time course of phosphorylation of its tyrosines, showed a marked difference: while PLC gamma 1 tyrosine phosphorylation, in the parental cells, was only transient (detected already 1 min after antigen addition and declined afterwards to basal levels at ca. 10 min), in the MAFA-deficient cells, tyrosine phosphorylated PLC gamma 1 was also observed 1 min after antigen addition, yet showed no decrease with time in its phosphorylation intensity for up to 30 min.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1452198 TI - Inhibition of murine erythroleukemia cell differentiation by normal and partially deleted c-myc genes. AB - In our study of normal and partially deleted myc genes we found that N-myc, similarly to L-myc, can substitute for c-myc and inhibit MEL cell differentiation. All of the known putative functional domains of c-myc seem to be required for this inhibition. It is conceivable that c-myc inhibits differentiation by a mechanism that is related to its normal role in the cell, possibly by regulating transcription of genes involved in growth promotion. As was previously found for all of the other known activities of c-Myc, the HLH and LZ dimerization motifs are absolutely necessary for inhibition of MEL cell differentiation. Heterodimerization of Myc with Max or Max-like proteins could be a prerequisite for such inhibition. It is, therefore, of interest to study the regulation of max in MEL cells expressing normal and deregulated myc genes. PMID- 1452199 TI - Polymorphism of the human Fc gamma receptor II (CD32): molecular basis and functional aspects. PMID- 1452200 TI - Calcium signalling by the high affinity macrophage Fc gamma receptor requires the cytosolic domain. AB - Hematopoietic cells express multiple receptors which bind the Fc domain of IgG. We utilized transfection of COS-1 cells, a cell line which lacks endogenous Fc receptors, to study the expression and function of Fc gamma RI, the high affinity Fc gamma receptor in the absence of other Fc gamma receptors. Fc gamma RI was efficiently expressed in transiently transfected COS-1 cells as measured by flow cytometry and the binding of IgG sensitized RBCs (EA). In addition, analysis at the single cell level demonstrated that individually transfected COS-1 cells release cytosolic free Ca2+ [(Ca2+)i] upon activation with anti-Fc gamma RI antibody. The calcium response required Fc gamma RI cross-linking. COS-1 cells transfected with mutant Fc gamma RI lacking the cytosolic domain expressed Fc gamma receptors and bound EA as well as wild type receptors, but failed to induce an increase in [Ca2+]i. These data indicate that Fc gamma RI in the absence of other Fc gamma receptors mediates a calcium signal and that the cytoplasmic domain of Fc gamma RI contains the elements required for calcium dependent signal transduction. PMID- 1452201 TI - Induction and function of Fc epsilon RII on YT cells; possible role of ADF/thioredoxin in Fc epsilon RII expression. AB - The regulation of low-affinity Fc receptor for IgE (Fc epsilon RII) and the characteristics of both membrane and soluble forms of Fc epsilon RII were studied using YT cell line. We found that YT cells, a human NK like cell line, expressed Fc epsilon RII after IL-1 stimulation. Cross-linking of Fc epsilon RII on IL-1 stimulated YT cells as well as the transfectant of Fc epsilon RII-cDNA (YTSER) resulted in the up-regulation of IL-2R alpha (p55/Tac). A 59 kDa protein phosphorylated at tyrosine residues was co-immunoprecipitated with Fc epsilon RII from YTSER lysate using H107 anti-Fc epsilon RII mAb. YTSER not only expressed Fc epsilon RII on their surface but also secreted soluble form of Fc epsilon RII (sFc epsilon RII/sCD23; IgE binding factor). Affinity purification revealed that sFc epsilon RII released from YTSER is heterogeneous and consisted of several proteins differing in molecular weight. Both EBV+ B cells and HTLV-1+ T cells are high producers of ATL derived factor (ADF)/thioredoxin (TRX) and express Fc epsilon RII and IL-2R alpha respectively. To clarify the mechanism of Fc epsilon RII and IL-2R alpha induction by ADF/TRX, we examined the effect of ADF/TRX on the bindability of nuclear factor kappa B (NF-kappa B), which is known to regulate IL-2R alpha gene expression. In the gel shift assay, ADF/TRX was shown to enhance the bindability of NF-kappa B to its responsive element. PMID- 1452202 TI - Soluble Fc gamma R (sFc gamma R): detection in biological fluids and production of a murine recombinant sFc gamma R biologically active in vitro and in vivo. AB - Soluble forms of receptors for the Fc portion of IgG (sFc gamma R) were detected in biological fluids from mice and humans. In mouse bearing tumors, circulating amounts of sFc gamma R increased concurrently with tumor growth. Tumors secreting IgG2a, IgG2b or IgG3 led to a 5- to 10-fold increase in serum sFc gamma R levels whereas tumors secreting IgG1, IgGA or other types of tumors (non Ig B cell tumors, T cell lymphoma and a melanoma) increased 2- to 3-fold the levels of circulating sFc gamma R. In the human, sFc gamma R were also detected in whole unstimulated saliva. Levels of sFc gamma RII and of sFc gamma RIII were variable and did not seem to depend on the dental status of the individuals. Finally, a murine recombinant sFc gamma R (rsFc gamma R) composed of the two extracellular domains of Fc gamma RII was produced by culture of transfected L cells in bioreactors. The purified rsFc gamma R was found to inhibit antibody production in vitro in anti-SRBC responses and by cultures of small B cells stimulated by anti-IgM antibodies in the presence of IL-4 and IL-5. Moreover, the i.p. injection of this material into adult mice immunized with SRBC led to a decrease of IgG antibody production by splenocytes, as measured by a hemolytic plaque assay, and in serum, as measured by antigen-specific ELISA. PMID- 1452203 TI - Two distinct regions of the mouse beta Fc gamma R gene control its transcription. AB - The low-affinity receptors for the Fc portion of IgG (Fc gamma RII and Fc gamma RIII) are born by most of the immunocompetent cells and mediate a wide spectrum of biological activities. Macrophages, mast cells and lymphocytes express the type II Fc gamma R whereas the type III Fc gamma R is expressed on macrophages, mast cells and NK cells. In mice, the beta Fc gamma R gene codes for Fc gamma RII and the alpha Fc gamma R gene codes for the ligand-binding Fc gamma RIII alpha chain. We have previously demonstrated that the methylation of the 5' region of these genes control their expression. In the present paper, we investigate the role of two unmethylated regions of the beta gene, the promoter and the third intron, in the control of its transcription. We show, by using two cell lines representative of B and mast cells, that different promoter fragments determine, in these two cell types, the transcription of the beta Fc gamma R gene. The third intron of the beta Fc gamma R gene contains sequences, which, introduced upstream to homologous or heterologous promoter, inhibit the transcriptional activity of these promoter. Thus, in B cells and in mast cells, the transcription of the beta Fc gamma R gene is controlled by two distinct regions of the gene. PMID- 1452204 TI - Lymphocyte Fc receptors: the immunobiology and pathology of CD23. PMID- 1452205 TI - TCR induced expression of Fc receptors on murine T cell subsets in vitro and in vivo. PMID- 1452206 TI - Autocrine regulation of murine B lymphocyte growth by an IgM antibody. AB - Culture supernatants of LPS-stimulated murine B lymphocytes are able to inhibit the growth of freshly isolated splenic B cells via an IgM antibody. The binding specificity of this IgM is not yet defined, but appears to be a B lymphocyte surface structure distinct from membrane immunoglobulin, MHC class II antigen, transferrin and Fc gamma receptors, and B220. The regulatory autoantibody allows the normal progression of early, but not late steps in the cycle of polyclonally stimulated B lymphocytes and does not affect the increased antigen-presenting capacity of activated B cells. Therefore, this autoregulatory cycle is apparently ubiquitous and may be a major component of B lymphocyte homeostasis under physiological, as well as pathological conditions. Moreover, these findings bring into focus a possible regulating role of B lymphocytes in the humoral immune response. PMID- 1452207 TI - Restriction mechanisms of B cell regulation by a physiological IgG-anti immunoglobulin autoantibody. AB - Immunization of LEW rats with strongly histoincompatible BN blood cells induces, in addition to anti-donor antibody, a broadly reactive IgG autoantibody which binds to IgG and IgM molecules (IgG anti-Ig). Minute amounts of affinity purified IgG anti-Ig (0.2 pg/10(6) cells) suppress the antibody production in vitro of antigen receptor (AgR)-stimulated B cells derived from rats of the same strain. The suppressive antibody is also active in the whole serum IgG fraction. Importantly, anti-Ig-induced suppression is governed by restriction mechanisms: only AgR-occupied B cells are affected, the suppression is cell cycle dependent, and maximum suppression is obtained at an optimum IgG concentration. Treatment of rats in vivo with 0.8 mg Ig-anti-Ig (whole IgG fraction) along with allogeneic cells resulted in nearly complete suppression of the anti-donor antibody response. Possible mechanisms of B cell suppression by IgG anti-Ig are crosslinking of AgR with FcR, or cocapping of the two receptors with sterical interaction as a consequence of their separate occupation. Both alternatives lead to the release of an inactivating signal. PMID- 1452208 TI - Macrophage-bound C3 fragments as adhesion molecules modulate presentation of exogenous antigens. AB - The involvement of complement in the response to T cell dependent antigens is generally accepted, however the mechanism has not been clarified. We compared the T cell response in vitro, using antigen-pulsed macrophages from normal and genetically C3-deficient guinea pigs, and show, that C3-fragments fixed covalently to the surface of the antigen-presenting cells are involved in the triggering of responder T cells. Binding of guinea pig C3-specific mAb to oil elicited, OVA- and PPD-pulsed macrophages of C3D guinea pigs is reduced compared to normal cells, while the expression of Ia antigens is the same. C3-like peptides can be immunoprecipitated only from the lysate of oil-elicited normal cells. These C3-fragments are fixed to the cell-membrane via ester-bonds, since they are released upon treatment with hydroxylamine. In comparison with normal cells, the antigen-presenting capacity of macrophages derived from C3D animals is strongly impaired in cultures containing 10% normal guinea pig serum. A further impairment is observed in cultures with 10% C3D guinea pig serum. Two of the tested C3-specific mAb inhibited antigen-induced T cell proliferation in a dose dependent manner. Our data point to the importance of C3, as a bivalent molecule, having the capacity to facilitate the cooperation between the antigen-presenting cell and the responder T lymphocytes. PMID- 1452209 TI - Dynamic physical interactions of plasma membrane molecules generate cell surface patterns and regulate cell activation processes. AB - Molecular interaction and transmembrane signal transducing events generate a very dynamic and ever changing "pattern" in the plasma membranes. Lymphocytes, the key functional elements of the immune system, are eminently suited to be the primary targets to investigate these proximity, mobility, or other physical-chemical changes in their plasma membranes. Recently, a number of experiments suggested that processed peptides from antigens can bind specific components of MHC molecules (Elliott et al., 1991). This is certainly a way to alter their structure. Cell surface patterns of topological nature, assembly and disassembly of oligomeric receptor structure like the IL-2 receptor have been investigated by sophisticated biophysical techniques. The dynamic changes in the two-dimensional cell surface pattern and intramolecular conformational changes within this "larger" macro-pattern may have a strong regulatory role in signal transducing and intercellular recognition processes. Recent data on these problems are presented together with brief and critical discussions. PMID- 1452210 TI - Detection of cytokine receptors by high-sensitivity immunofluorescence/flow cytometry. AB - Cytokines have profound effects on cells, and act through receptors which need only be at low concentrations (around 100 copies per cell) to transmit activation signals. The detection of such low concentrations is possible using monoclonal antibodies and fluorescence/flow cytometry, but only by using specialized techniques. The best results so far have been obtained using biotinylated second antibody followed by phycoerythrin-streptavidin, and batches of these reagents have to be carefully selected. Analysis of the fluorescence is best done using 546 nm excitation from a mercury arc lamp, but 512 nm excitation from an argon ion laser can also be used. With appropriate alignment, instruments with 488 nm fixed-wavelength lasers can give sensitivity almost as good as the 546 nm system. Working at high sensitivity, background levels also increase, particularly for B lymphocytes. Background staining can be reduced to acceptable levels by blocking the two major mechanisms for non-specific binding. Applications of these methods to the detection of cytokine receptors on normal and malignant cells are reviewed. PMID- 1452211 TI - In vivo and in vitro death of mature T cells induced by separate signals to CD4 and alpha beta TCR. AB - To investigate whether a clonal deletion mechanism is responsible for the mature T cell tolerance that may be induced in vivo by TCR signal to anti-CD4 (H129.19 mAb) coated cells, we analyzed the T cell repertoire in anti-CD4 mAb treated BALB/c mice by flow cytometry following TCR signals through anti-alpha beta TCR mAb or SEB superantigen. Lymph nodes showed a strong reduction in the CD4+/CD8+ cell ratio, and a selective clonal loss of CD4+ V beta 8+ cells 4d following anti alpha beta TCR or SEB injection, respectively. Following lymph node cell activation in a short-term in vitro assay with SEB or anti-V beta 8 mAb, a selective elimination of CD4+ V beta 8+ cells was again detected, and DNA fragmentation analysis disclosed a cell death by apoptosis. These findings suggest that TCR triggering transduces an apoptotic signal into CD4+ mAb saturated cells that in turn leads to specific holes in the mature T cell repertoire. PMID- 1452212 TI - Targeting of anti-tumor responses with bispecific antibodies. AB - T cells can be induced to specifically lyse tumor cells with bispecific antibodies containing anti-T cell receptor mAbs crosslinked to anti-tumor mAbs. Such "targeted cytolysis" requires that the target cell be bound directly to the cytotoxic cell. In addition, targeted T cells mediate a second activity, the secretion of factors that can block the growth of both tumor target cells and bystander tumor cells. When given to nude mice bearing intraperitoneal human ovarian carcinoma, targeted human T cells cause the rapid removal of most tumor cells from the peritoneum, and markedly prolong the times of survival of treated mice. The efficacy of targeted T cells for treating human cancer is currently being tested in clinical trials. PMID- 1452213 TI - Possibilities of interference with the immune system of tumor bearers by non lymphoid Fc gamma RII expressing tumor cells. AB - The ectopic expression of Fc gamma RII by PyV transformed 3T3 cells derived from tumors of long latency has been established. It was suggested that this expression is one of several changes conferring upon the cells an increased capacity for survival. We found that in one case cells expressing a very high level of Fc gamma RII had also a very high metastatic phenotype as compared to FcR negative cells. Direct evidence that Fc gamma RIIbl functions as a progression factor was provided by transfection experiments. The transfected gene conferred an increased malignancy and invasive phenotype upon PyV or c-Ha-ras transformed cells. In the present study we tested the possibility that Fc gamma RII expressing tumor cells could interfere with the immune system. The following subjects were investigated: 1) The ability of Fc gamma R on the tumor cells to bind the ligand and/or release IBF. 2) The effect of a local accumulation of ligand and/or IBF (assumed to take place in situ in the tumor) on Fc gamma RII expressing T cells. It was found that both tumor-derived receptor positive and beta l transfected PyV transformed cells were capable of binding aggregated mouse IgG. The binding of bivalent ligand was followed by an increase in membrane Fc gamma RII expression. Also both types of cells were capable of releasing IBF. We then tested the possibility that a local accumulation of IgG within the tumor could effect Fc gamma R expressing T cells. It was found that aggregated mouse IgG (as well as IgGl) could stimulate the proliferation of the T cell hybridoma (T2D4) and other Fc gamma RII expressing T cells. We also found that the expression of beta Fc gamma RII specific mRNA peaked at the logarithmic phase of T2D4 cultures, in parallel with their maximal potential to release IBF. Several pathways for interference with the immune system are suggested. PMID- 1452214 TI - Tumor growth changes the contribution of granulocyte-macrophage colony stimulating factor during macrophage-mediated suppression of allorecognition. AB - Tumor-bearing host (TBH) macrophages (M phi) suppress T cell alloresponses, and this study suggests granulocyte-macrophage colony-stimulating factor (GM-CSF), a molecule associated with suppressive M phi activity during tumor growth, signals more immunosuppression. In the absence of M phi, GM-CSF increased T cell proliferation in response to alloantigen. However, TBH M phi-mediated suppression of allorecogntion was further induced by GM-CSF. Allogeneic mixed lymphocyte reaction (MLR) cultures, containing normal host (NH) M phi, were either unaffected or enhanced. Prostaglandin E2 (PGE2), a highly suppressive monokine that decreases alloreactivity, did not seem to be involved in the suppression caused by the TBH M phi/GM-CSF interaction. M phi-CSF (M-CSF) addition to cultures did not reverse the suppression caused by TBH M phi and GM-CSF, and inhibition of PGE2 synthesis did not change the response to M-CSF. TBH Ia- M phi, a suppressor population that predominates among splenic M phi during tumor growth, demonstrated significantly lower reactivity in the presence of GM-CSF. In contrast, alloresponses suppressed by NH Ia- M phi demonstrated higher reactivity in the presence of GM-CSF. The data collectively suggest that TBH M phi respond differently to GM-CSF, and that tumor-induced changes in GM-CSF responsiveness affect M phi accessory ability. PMID- 1452215 TI - HLA molecules in basal cell carcinoma of the skin. AB - Fifty basal cell carcinomas (BCC) and 8 samples of healthy skin were studied for HLA class I and class II antigen expression and for the presence of mutations in codon 12 of the K-ras and H-ras genes. All samples of healthy skin and of epithelium near the tumor showed high levels of class I molecules, whereas 38% of the tumors showed complete absence. Sixty-two percent of the tumors presented positive class I expression with heterogeneous staining. These losses were due to the simultaneous lack of heavy chain and beta 2-microglobulin. Selective losses of HLA-A or HLA-B antigens were not detected. Class II antigens were absent in most of the tumors, only two tumors showing a few weakly positive cells with anti HLA-DR mAb. The loss of class I expression correlated significantly with the degree of histological differentiation and aggressiveness. We were unable to correlate class I expression with clinical size, depth of invasion or the extent of leukocytic infiltrate surrounding the tumor. Analysis by PCR amplification of codon 12 of the K-ras and H-ras oncogenes detected H-ras mutations in 1 out of 50 cases, and no K-ras mutations in any of the tumors studied. Thus, a positive relationship between K-ras and H-ras mutations and BCC tumorigenesis or MHC alterations seems unlikely in this neoplasia. PMID- 1452216 TI - Differences of two Borrelia burgdorferi strains in complement activation and serum resistance. AB - Complement activation and serum resistance of the Borrelia burgdorferi strains B31 (American strain) and PKo (European strain) were compared. In 25% (v/v) normal human serum (NHS) free of B. burgdorferi-specific antibodies the cells of the PKo strain were high activators of complement as indicated by rapid and strong C9 consumption, by deposition of up to 336763 C9 molecules per cell and by the formation of the terminal complement complex on the cell surface. By comparison, complement activation by the B31 strain was low with 5.4-fold less C9 deposited per cell. The addition of B. burgdorferi-specific antibodies to NHS either as purified IgG or heat-inactivated patient sera, had no influence on the results with both strains. After an incubation period of 2h at 37 degrees C in 25% (v/v) NHS most cells of the PKo strain had lost their viability as indicated by cell immobilization and failure to multiply in subcultures. In addition, extensive cell fragmentation and bleb formation were observed in the electron microscope. In contrast, the B31 strain remained alive and morphologically intact after the same incubation with NHS. We conclude from our results that complement activation and serum resistance are properties which differ considerably between isolated strains of B. burgdorferi. PMID- 1452218 TI - Proceedings of the Australasian Society for Experimental Pathology. 24th annual meeting. Sydney, 28 September-1 October 1992. Abstracts. PMID- 1452217 TI - T cell receptor variable region repertoire in lymphocytes from rheumatoid arthritis patients. PMID- 1452219 TI - Burnet oration. Autoimmunity: paradigms of Burnet and complexities of today. PMID- 1452220 TI - Evaluation of thrombus detection in a rabbit model using a technetium-99m labelled anti-fibrin monoclonal antibody. AB - Technetium-99 m (99mTc)-labelled conjugates of an anti-fibrin monoclonal antibody, DD-3B6/22, have been assessed for their detection of vascular thrombi in a rabbit model. DD-3B6/22 binds to a D-dimer epitope present on cross-linked fibrin but absent from the fibrin monomer or fibrinogen. Injection of a 99mTc labelled Fab' fragment of DD-3B6/22 allowed delineation of model thrombi as early as 30 min postinjection (p.i.) with optimal localization at 4-5 h. Thrombus label uptake at 4 h p.i. was 0.304 +/- 0.106% injected dose/g (% ID/g) compared with 0.022 +/- 0.001% ID/g after the injection of a control Fab' fragment. These results suggest that the 99mTc-labelled Fab' fragment of DD-3B6/22 has excellent potential for scintigraphic detection of vascular thrombi in humans. PMID- 1452222 TI - Structural basis of antigenic variation: studies of influenza virus neuraminidase. PMID- 1452221 TI - Western blot analysis of antibody responses to influenza virion proteins. AB - An immunoblotting procedure was developed to detect antibody responses in mice and humans to influenza virion proteins. The technique was capable of detecting 1.5 micrograms of haemagglutinin (HA) on nitrocellulose strips at a 1:5000 dilution of a mouse serum with an initial haemagglutination inhibition titre of 20. The effects of the use of the blocking agent Tween-20 on virion proteins were also studied. The commonly used concentration of 0.05% (v/v) Tween-20, when included in blocking and incubation buffers, greatly reduced the amount of detectable matrix protein but caused no detectable loss of HA and neuraminidase/nucleoprotein proteins. If virion proteins were separated by polyacrylamide gel electrophoresis under reducing conditions, antibody bound to HA2 more strongly than to HA1. Under non-reducing conditions, more antibody bound to the uncleaved HA protein than to other proteins. IgG1 and IgG2a antibody responses in mice to each protein were stronger than IgG2b and IgG3 responses. PMID- 1452223 TI - Diversity and variation in human immunodeficiency virus: implications for immune control. PMID- 1452224 TI - Sporostatic effect of some oils against fungi causing otomycosis. AB - In vitro animycotic effect of mustard, groundnut, soybean, coconut and amla oils on five fungi i.e., Aspergillus niger, A. flavus, Absidia corymbifera, Penicillium nigricans and Candida albicans isolated from otitic fungal infection of external ear (Tympanic membrane) of human being was studied. Spore germination was evaluated in the oil samples as such after heating for two minutes & after boiling the oil. Data show that mustard and coconut oil seem to be effective as in these the spore germination was poor. Other oils were not found to be much effective. Sporostatic effect was noted only when the oils were used after heating or boiling this may be correlated by the synthesis of enzymes during spore germination. PMID- 1452225 TI - Results of pars plana vitrectomy in 62 cases of vitreous haemorrhage. AB - 62 Cases with unresolving Vitreous Haemorrhage due to varied etiology, underwent pars plana Vitrectomy. A vitreous rebleed on the table and post-operatively, was the main complication encountered. Despite limited equipment, a visual improvement was obtained in 59.68% eyes with visual acuity greater than FC 6 meters in 33.87% eyes. This is far better than not being able to offer any treatment at all. PMID- 1452226 TI - Cholesterol can curb heart attacks: study. PMID- 1452227 TI - Changes in pulmonary diffusing capacity and blood gases in chronic obstructive lung diseases. AB - Pulmonary diffusing capacity (TLco) of 19 cases of chronic obstructive lung diseases (Chronic obstructive bronchitis and chronic obstructive emphysema) in the age group of 39 to 58 years (mean age: 49.8 +/- 5.5 SD years) are reported at rest in this investigation. The diffusing capacity for carbon monoxide (TLco) measured by standard methods was significantly reduced in all cases. The mean was 13.1 +/- 2.3 SD ml/min/mmHg. The blood gas findings revealed low arterial oxygen saturation (mean value: 90.2 +/- 2.2%). Arterial carbon dioxide tension was higher than in normal subjects. The mean for this series was 44.8 +/- 4.9 SD mmHg. The mean for normal subjects was 37.5 mmHg and the range 28.2 to 41.5. PMID- 1452228 TI - Effect of different levels of iron supplementation on the iron status and physical work capacity of anaemic Indian women. PMID- 1452229 TI - Differential identification of Mycobacterium tuberculosis from various clinical specimens from Sassoon General Hospital, Pune. AB - A total of 619 clinical specimens from cases of pulmonary and extrapulmonary tuberculosis were processed by smear, culture and biochemical tests. Acid fast bacilli could be demonstrated in 93 samples (15.02%) by Z.N. staining method. Culture yielded positive growth in 95 samples (15.35%) M. tuberculosis human type was the most predominient pathogen obtained from 82 cultures (13.40%) M tuberculosis bovine type was isolated from 2 cases of ascitic fluids (0.32%). Atypical Mycobacteria were isolated from 11 samples (1.73%). 5 turned out to be M. scrofulacium, 4 were M. Kansasii, 1 was M. phlei and 1 was M. smegmatis. PMID- 1452230 TI - Study of bacterial pathogens causing diarrhoeal disease in Bombay with special reference to their antibiotic sensitivity pattern. AB - Diarrhoeal disease is an important cause of morbidity and mortality in developing countries, especially among children. In a study of 720 faecal samples from acute diarrhoeal patients various bacterial pathogens were isolated. An account is given of their antibiotic sensitivity pattern. Many of the E. coli, Salmonella and Shigella strains were found to be multidrug resistant. This resistance was transferable and plasmid mediated. A few of the E. coli strains isolated from healthy controls also showed multidrug resistance. PMID- 1452231 TI - WHO commends India. PMID- 1452232 TI - Low-dose pill is launched. PMID- 1452233 TI - High salt intake can cause gastric cancer. PMID- 1452234 TI - Correlation of microproteinuria and histopathological changes in kidney in diabetes mellitus. AB - Single attempt kidney biopsy was successful in 60 cases of diabetes mellitus out of 83. Histopathological evidence of nephropathy was found in 30 (50%) out of 60 (4 of IDDM and 56 of NIDDM). Microproteinuria was a sensitive indicator of histopathological evidence of nephropathy (by biopsy) and should be used as a non invasive method of evidence of kidney involvement in diabetes mellitus regardless of duration of the disease. Routine renal function tests--commonly used indicators of kidney disease in the presence of hypertension were of no value and should not be relied upon. Duration of diabetes mellitus was important correlation with the evidence of the disease and and its severity but nephropathy was found in newly detected cases of diabetes mellitus (NIDDM). Nephropathy was present in case of DM who had retinopathy and is a better factor of correlation. PMID- 1452235 TI - Development outcome of Down's syndrome in eastern Libya. AB - The psychometric evaluations in 60 cases of Down's syndrome non-institutionalized children in the age group 1-15 years drawn after random selection was compared with 60 children with mental handicap from a residential institution drawn by matching for age, sex and sociocultural conditions. Results of the study show significant difference between the two groups in respect to IQ's but not in respect to DQ's. PMID- 1452236 TI - Neutral sterol excretions in rats fed skim milk and skim milk yogurt diets. AB - Acceleration of cholesterol catabolism (through feces) has been proposed as one of the mechanisms for the hypocholesterolemic effect of dairy products. This study examined the effects of feeding two milk products (skim milk and skim milk yogurt) on fecal neutral sterol excretions in rats. Six groups of nine rats each were fed iso-caloric Chow-based diets containing water, 45% skim milk (SM), or 45% skim milk yogurt (SMY), without or with cholesterol. The results indicate that both SM and SMY increased the excretion of total neutral sterols under hyperlipemic conditions. The SMY diet (with cholesterol) also increased the excretion of coprostanol, a bacterial metabolite. PMID- 1452237 TI - National quality control programme in Indian clinical laboratories. PMID- 1452238 TI - An epidemic of human anthrax--a study. AB - Twenty-five cases of human anthrax, occurring after contact with a Jercy cow infected with B. anthracis and consumption of its improperly cooked meat after death, were reported. Cutaneous anthrax was the predominant variety in 18 persons, 7 had intestinal anthrax, out of them 2 children died, 5 adults survived and one among them developed associated cutaneous anthrax also. All the persons with cutaneous anthrax recovered with treatment. PMID- 1452239 TI - Chloramphenicol resistant Salmonella typhi: the cause of recent out-break of enteric fever in Calcutta. AB - Fifty one strains of Salmonella typhi were isolated during the recent outbreak of enteric fever in and around Calcutta. Forty strains were multidrug resistant including Chloramphenicol. Minimum inhibitory concentrations (MIC) of Chloramphenicol was between 200 mcg per ml and 500 mcg per ml. All these strains were sensitive to Cephalexine, Gentamicin, Furazolidine and Ciproflexacin. Widal test was done in all the cases but the result was inconclusive. PMID- 1452240 TI - Quantitative immunological status of males of unexplained infertility in eastern U.P. AB - 126 males of unexplained infertility and 75 fertile males were studied during a period of more than 2 years. Statistically significant increase in the levels of serum IgM was observed in cases of males of unexplained infertility. Level and percentage of cases showing semen IgM was more in study group (134.61 +/- 25.5 mg %, 41.26%) than control (24%, 99.3 +/- 8.3%). Semen IgA was found only in study group in 30.15% cases. Though definite correlation between serum and semen immunoglobulin was not observed, semen immunoglobulin was found to be 1-2 fold lower than serum. Results of the present study indicate towards a possible immunological role in cases of unexplained infertility in males. PMID- 1452241 TI - A preliminary study on the interaction of cell-polymer extract towards biodegradation. AB - Two newly synthesised polyurethanes were subjected to a preliminary study, in vitro, on the interaction of cell polymer extract to understand the phenomenon of biodegradation by employing VERO cells. VERO cells exposed to the saline extract of the polymer showed cytopathic effect with granulations in the digestive vacuoles. It is suggested that the long term material performance of an implant material can be evaluated by using VERO cells and/or macrophages and by analysing metabolic products secreted by the cells during interaction. PMID- 1452242 TI - Frozen sections--a retrospective study. AB - Two hundred and forty-four (244) specimens were examined by frozen section (FS) from 1987 through 1988 at the Kidwal Memorial Institute of Oncology. Of these, eleven (11) were performed for evaluation of the surgical margin of tumours and fifty four (54) for detection of lymph node metastasis. All these examinations (65) proved to be hundred percent (100%) accurate. The remaining 179 frozen sections were performed for the diagnosis of an unknown pathologic process. Of these, 44.69 percent were precisely diagnosed, in 41.9 percent the pathologic process was correctly but not precisely diagnosed, in 11.17 per cent the diagnosis was deferred and remaining 2.24 percent were incorrectly diagnosed with no harmful consequences to the patients. By eliminating the cases where diagnosis was deferred and combining results of "precise diagnosis" with those of "correct pathologic process", the overall accuracy rate was 98.2 percent. Thus, FS has greater benefit when used for the general diagnosis of an unknown pathologic process rather than for an exact or precise diagnosis. PMID- 1452243 TI - Identification of family Enterobacteriaceae using a three tube method. AB - Four hundred isolates of Gram Negative bacilli from different samples were tested by three tube method and conventional tests. An overall agreement between the two methods was 89.5%. Non-agreement was in respect of less stable tests like gas production and motility. This does not reflect adversely on the efficacy and suitability of the method. The three tube method is simple, rapid, economical and accurate, saving both time and material. PMID- 1452244 TI - Chronic granulomatous mastitis: review of 26 cases with special reference to chronic lobular mastitis. AB - Twenty six cases of chronic granulomatous mastitis are reported in a 5 year period and the slides are reviewed. They are sub-classified into Chronic lobular mastitis (CLM), Plasma cell mastitis and subareolar granuloma. There are 10 cases each of CLM and plasma cell mastitis and one of subareolar granuloma. All the three conditions are associated with duct ectasia. Fat necrosis and infective granulomas were 2 each and one of foreign body granuloma. These lesions can be easily differentiated by histology. While most of the CLM occurred in younger age group, plasma cell mastitis is seen in older women. Histologically, there is a florid inflammatory cell reaction of the stroma with dilatation and destruction of some ducts, with microabscess formation. In plasma cell mastitis, the lesion is more chronic with predominance of plasma cells and involutionary changes of the ducts are seen. PMID- 1452245 TI - MHA-Tp testing on HIV positive and negative women in vigilance home at Madurai. AB - In the study group of 94 cases of female prostitutes and their children 55 cases showed positive for HIV infection by ELISA and Western Blot tests. They showed positive also for syphilis in 37 cases by VDRL and in 43 cases by MHA-Tp tests among HIV positive and negative women. The association of HIV infection and syphilis was observed in this study due to sexual transmission of these infections. But congenital spread from infected mother to their children was not observed in this study since both mothers and their children were negative for these infections. MHA-Tp testing confirmed VDRL test results in 27 cases and also increased specificity of MHA-Tp test result over VDRL result in 16 cases and exclusion of biological false positive by VDRL in 10 cases were noticed in this study. PMID- 1452246 TI - Serum adenosine deaminase activity in bacillary or paucibacillary pulmonary tuberculosis. AB - Serum Adenosine Deaminase (ADA) enzyme levels were estimated in 61 patients with symptoms and signs suggestive of Pulmonary Tuberculosis and correlated with "Gold standards" such as smear positivity of sputum for Acid Fast bacilli, Tuberculin skin testing and Radiological evidence. The mean ADA levels in smear and Tuberculin negative patients was 13.13 +/- 5.97 u/L, while in those with smear and/or strongly positive Tuberculin reaction, the mean levels of ADA were 33.52 +/- 15.22 u/L. The mean serum ADA levels in 25 healthy voluntary donors with no evidence of active or old Tuberculous lesion, were found to be 16.5 +/- 3.18 u/L. The specificity, sensitivity, positive predictive value and negative predictive value of the test was found to be 87%, 71%, 90% and 66.5% respectively. The results conclude that the serum ADA value is sufficiently useful in identifying those patients in whom the diagnosis of Pulmonary Tuberculosis should be actively considered. PMID- 1452247 TI - A study of humoral factors in carcinoma cervix. AB - Serum immunoglobulins, circulating immune-complexes and blocking effect of patients' sera on normal T lymphocytes were studied in 10 patients with chronic cervicitis, 25 with carcinoma cervix and 20 age matched healthy women. No significant difference was observed between the healthy controls and chronic cervicitis. In carcinoma, there was a significant increase in IgG and IgA in stage I, IgG and IgM in stage II and in all the three immunoglobulins in stage III as compared to chronic cervicitis. Circulating immune-complexes and T cell depression were also found to be increased and stage related. After radiotherapy, both these parameters and IgG were found to be significantly reduced. The study of these immune parameters seems to be a promising aid in the diagnosis and prognosis of patients with carcinoma cervix. PMID- 1452248 TI - Epithelioid sarcoma of the thigh--a case report. PMID- 1452249 TI - A case of hitherto unreported cutaneous geotrichosis from India. PMID- 1452250 TI - Leydig cell tumour of testis--a case report. PMID- 1452251 TI - Primary malignant haemangiopericytoma of lung--a case report. PMID- 1452252 TI - Extensive fatal bone marrow necrosis in typhoid fever. PMID- 1452253 TI - The perinatal autopsy. PMID- 1452254 TI - Hairy cell leukemia (HCL) PMID- 1452255 TI - Bellagio brief on vitamin A deficiency. PMID- 1452256 TI - Hemostatic profile in septicemic neonates with and without bleeding. AB - Hemostatic profile was studied in 25 full term, non-asphyxiated neonates with blood culture-proven septicemia. Nine (36%) of these neonates manifested bleeding. Detailed coagulation tests and platelet studies were deranged in 24 (96%) of neonates with septicemia. Abnormalities in coagulation tests did not differ in those with and without bleeding. Only platelet aggregation with ADP was deranged to a significantly greater extent in those with bleeding as compared with those without bleeding. PMID- 1452257 TI - Hepatitis B virus infection in pregnant mothers and its transmission to infants. AB - Screening for serological markers of hepatitis B virus infection was done on 500 pregnant mothers. HBsAg, AntiHBs and HBeAg were done. HBsAg was positive in 3.6%, AntiHBs in 17.4% and HBeAg in 0.4% cases. The infants born to the asymptomatic HBsAg carrier mothers were followed up to 6 months to determine the vertical transmission of HBV infection. Rate of transmission of infection from HBsAg positive mothers to infants were 16.66% irrespective of HBeAg status, whereas it was nearly 100% in case of HBeAg positive mothers. All of the HBsAg positive infants developed the antigenemia between 3-6 months of age, supporting the hypothesis that intrapartum transmission is the major mode of vertical transmission. PMID- 1452258 TI - A screening tool for assessment of the home environment and psychosocial development of preschool children. AB - The purpose of this study was to develop a short tool for the assessment of home environment and psychosocial development of preschool children, based on the data collected on a sample of one hundred and fifty children in the age range of 2 years 10 months to 3 years 8 months. Co-relation analysis was used in identifying home environment and psychosocial development variables for the development of the tool. PMID- 1452259 TI - Epidemiological aspects of school dropouts in children between 7-15 years in rural Maharashtra. AB - A study on school dropouts from primary and secondary school children was undertaken in September '91 from 16 schools at the headquarters of 8 Primary Health Centres, where 172 school dropouts were identified. A home visit was paid and information about socio-economic and cultural aspects was collected and a psychological screening was undertaken. Although there was no significant difference in overall dropout rates for both sexes, it increased sharply at 11 years of age in girls. The majority of children dropped out due to financial problems or unsatisfactory scholastic performance, and 142 (82.5%) of the 172 children studied were poor performers in one or more function tests. Maximum difficulty was observed in concept formation 87 (50.5%), followed by numerical ability in 78 (45%). Identification of children with learning difficulties and intervention using special educational methods within the framework of existing network of primary and secondary schools in rural areas is suggested. PMID- 1452260 TI - Psycho-social aspects of HIV infection and AIDS in multiple transfused thalassemic children. AB - Two hundred and three multi-transfused children with thalassemia attending the thalassemia clinic of the Charak Palika Hospital, New Delhi were screened for human immuno-deficiency virus (HIV) antibodies by ELISA test. All positive cases were confirmed by the Western blot test. Of the 203 children screened, 17 (8.37%) were HIV seropositive and the other 3 children referred to the AIIMS were from neighbouring states. These children were compared with 20 age matched HIV negative thalassemics as controls. Of the 20 HIV positive children, four were diagnosed to have clinical AIDS according to the WHO criteria. The clinical features were similar to those described in pediatric AIDS from other parts of the world. This paper describes the clinical features, behavioural problems, cognitive functions and developmental milestones of the children with AIDS. PMID- 1452261 TI - Pulmonary tuberculosis in Ahmedabad: epidemiology, diagnosis and short course chemotherapy. AB - Five hundred children below the age of 12 years suffering from lung tuberculosis viz., primary complex (PC) or progressive primary complex (PPC) were studied. Diagnosis was based on Kenneth Jones criteria; selected cases having score of 5 or more. One hundred and eighty cases of PC were given A-1 (6 RH) regimen, while 312 cases of PPC were given A-2 (2SHRZ/4 RH) or A-3 (2 SRH/4 RH) or A-4 (2 RHE/4 RH) regimen. Follow-up was done for 6 months after completing the treatment to observe the relapse rate. In cases of PC, 6 RH regimen appeared adequate and cheaper with no relapse rate. In cases of PPC with short course chemotherapy, compliance of patients had been very good. Relapse rate was up to 13% which is acceptable. Drug toxicity was very low. PMID- 1452262 TI - Childhood myelodysplastic syndromes: clinical features, cytogenetics and prognosis. AB - Sixteen children with myelodysplastic syndrome as defined by the French-American British co-operative group are presented. The mean age was 10.5 (2.5 to 16) years, with a male predominance. All patients belonged to the more aggressive subtypes of myelodysplastic syndromes. Seven patients presented with refractory anaemia with excess blasts, six had refractory anemia with excess blasts in transformation, and three had chronic myelomonocytic leukemia. Cytogenetic analysis done in 7 of the 16 patients, revealed karyotype abnormalities involving chromosomes 7, 8 and 17. One patient with Down's syndrome had karyotype of 47, XY, +21 (major clone) and 46, XY (minor clone). Five of these patients evolved to acute leukemia. The mean duration of survival was 5.5 months. Aggressive chemotherapy as a primary line of treatment induced remission in five out of six patients. Predominance of aggressive types of myelodysplastic syndromes in children and their good but short-lived response to aggressive chemotherapy suggests the need for early bone marrow transplantation following chemotherapy. PMID- 1452263 TI - Reproductive profile of mothers in relation to hemoglobin E genotypes. AB - The reproductive profile of 190 Ahom-Kachari mothers belonging to Mongoloid ethnic stock of Assam has been studied in relation to hemoglobin (Hb) E genotypes. No significant variations have been observed in the reproductive performance between the normal population and abnormal hemoglobin homozygote (HbEE) and heterozygote (HbAE) mothers. However, the reproductive wastage among the hemoglobin homozygote (HbEE) mothers has been observed to be double than the normal hemoglobin (HbAA) and abnormal hemoglobin heterozygote (HbAE) mothers. The reproductive performance parameters have also been compared with the other available studies. PMID- 1452264 TI - Risk factors for stillbirths in a rural community. AB - To determine the risk factors for stillbirth, a case-control study was carried out in a rural community of Haryana. Stillbirths (cases) were identified retrospectively from a household survey, while the controls, matched individually with each case for the month of birth, were live born infants from the same neighbourhood as the case. The stillbirth rate in the study population was 26.8 per 1000 (68/2539) births. The distribution of socio-economic and environmental factors was similar in the cases and the controls (P > 0.05). Multivariate analysis indicated higher risk of stillbirth for first order births (Odds Ratio [OR] 7.9, Confidence Interval [CI] 2.1-29.2, P 0.002), history of prior stillbirths/child deaths (OR 15.2, CI 2.3-98.2, P 0.004), and absence of antenatal care (OR 3.3, CI 0.9-14.3, P 0.07). Mothers' age, birth interval (< 24 months), delivery place (hospital or home) and type of birth attendant (trained vs untrained) did not show significant influence on the risk of stillbirth. An improvement in the coverage of antenatal care in socio-economically weaker rural community is suggested as the most appropriate strategy for reducing the high stillbirth rate. PMID- 1452265 TI - Intersex disorder associated with ambiguous genitalia. PMID- 1452266 TI - Embryology and classification of intersex states. PMID- 1452267 TI - Etiopathogenesis, classification, investigations and diagnosis in intersex disorders. PMID- 1452268 TI - Mixed gonadal dysgenesis and dysgenetic male pseudohermaphroditism--a critical analysis. AB - A 10 year prospective study of 14 patients with mixed gonadal dysgenesis (MGD) and six patients with dysgenetic male pseudohermaphroditism (DMP) is reported. All of them had internal mullerian structures, along with unilateral or bilateral dysgenetic testes, ambiguous external genitalia. Twelve had been brought up as male, nine of whom had a unilateral descended testis. Eight had been reared as females, as they had bilaterally undescended gonads, and ambiguous genitalia. Clinical examination, retrograde genito-urethrography and cytogenetic studies suggested the diagnosis in 16 patients, while four were diagnosed on inguino abdominal exploration for undescended testis. This report delineates more clearly the clinical profile of these orders. All the patients reared as male were assigned the male gender following abdominal gonadectomy, retention of scrotal testis and male genitoplasty. The eight patients who were reared as females underwent bilateral salpingo-gonadectomy and female genitoplasty. This management differs from the usual recommendation that all such children should be reared as females. Ten patients (50%) had maternal history of previous abortion/stillbirth, or drug intake in the first trimester of pregnancy suggesting a role of these factors in the etiology. All cases of DMP had a 46,XY karyotype, while eight of 14 cases of MGD had mosaicism with 45X/46,XY cell lines in blood or gonadal cultures. The clinicopathological features of patients of MGD and DMP were similar. It is suggested that these two disorders represent different spectra of the same disorder. A unifying concept of etiopathogenesis is proposed. PMID- 1452270 TI - Prenatal treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: a 10 year experience. PMID- 1452271 TI - Intersex disorders: an approach to surgical management. PMID- 1452269 TI - Steroid enzyme defects leading to male pseudohermaphroditism. PMID- 1452272 TI - Congenital adrenal hyperplasia: experience at intersex clinic, AIIMS. AB - During 1981-88, 63 cases of female pseudohermaphroditism (FPH) were seen at the Intersex clinic at AIIMS, of whom 34 (54%) were diagnosed as due to congenital adrenal hyperplasia (CAH). Though ambiguity was present at birth in most cases, only one child was brought immediately after birth, while 14 presented after one year. Family history of affected siblings and fetal wastage was present in 10. Salt wasting symptoms were present in 13 (38.2%), evidence of early virilization in 10 (29.4%) and generalised hyperpigmentation in 7 (20.6%). Clitoromegaly was present in 30 children with labial fusion in 10 and scrotalisation of labia in 6. The urogenital opening was single in 25 (73.5%). Buccal smear was positive for sex chromatin in 19. Chromosomal pattern showed 46 XX in 33. Dyselectrolytemia was present in 16 children. Bone age was advanced in all. Adrenal hyperplasia could be documented in 3 on CT scan. All the girls were put on hydrocortisone or prednisolone, and fluodrocortisone was given only to children with salt wasting CAH. Children with CAH are being brought to medical attention much too late and investigative and therapeutic facilities are grossly inadequate. There is a need to educate primary care physicians for early case detection and provide minimum diagnostic and therapeutic facilities in regional centres. PMID- 1452273 TI - Trisomy 18 evaluated by Marion's scoring system. PMID- 1452274 TI - Gastric teratoma--review of literature. PMID- 1452275 TI - Counselling concerns as related to familial vesico-ureteral reflux in two siblings. PMID- 1452276 TI - Urolithiasis in children. PMID- 1452277 TI - Parsplana surgery. PMID- 1452278 TI - Pars plana vitrectomy in vitreous haemorrhage due to Eales' disease. AB - Repeated vitreous haemorrhage is a common occurrence in Eales disease. 25 eyes of unresolving vitreous haemorrhage were subjected to pars plana vitrectomy. 18 eyes improved to 1/60 or better. Vitreous rebleed was the commonest problem encountered. We discuss our experience, complications and limitations. PMID- 1452279 TI - Vitrectomy for intra ocular foreign body removal. AB - Ten consecutive cases of perforating ocular injuries with retained intraocular foreign bodies over a period of 2 years were reviewed retrospectively in this study. All cases were operated upon by a 3 port pars plana vitrectomy and if necessary endolaser done. All ten cases (100%) were successful in terms of intraocular foreign body removal through the pars plana sclerotomy but ultimately we lost three [3] [30%] cases of which two had retinal detachments with P.V.R. D 3 preoperatively and the other had endophthalmitis. Of the seven (70%) successful cases four eyes (40%) had a post-operative vision of 6/12 or better while 2 [20%] had 6/24 and the last had 6/60 [10%]. Nine cases [90%] had a magnetic Intraocular foreign body. Various complications of Intraocular foreign bodies like vitreous haemorrhage, retinal incarceration, cataract and retinal detachment were noted preoperatively. Silicone oil was used in three (30%) cases. Sulfur Hexafluoride was used in 5 cases (50%). Endolaser photocoagulation was done in 7 cases (70%). PMID- 1452280 TI - Comparative results of limbal based versus fornix based conjunctival flaps for trabeculectomy. AB - Among 100 cases of primary glaucomas, 50 cases were operated for trabeculectomy by making fornix based flap and 50 cases were operated by fashioning limbal based conjunctival flap. Operative and post operative complications were studied thoroughly in the two groups. All the cases were followed up for six months to one year to assess control of intra ocular pressure, nature and functioning of filtering bleb, field changes and visual status in the two groups. It was found that the fornix based flap is much superior and carries various advantages over the limbal based flap. The operative and post operative complications are minimum in the fornix based flap as compared to the limbal based flap. PMID- 1452281 TI - "A retrospective cohort study for prognostic significance of visual acuity for near over that for distance in anisometropic amblyopia.". AB - A cohort of 50 anisometropic amblyopes, between the ages of 2.5 to 10 years, was studied retrospectively to assess the prognostic significance of visual acuity for near over that for distance. There is ample evidence in the literature for a significantly lower accommodative response in the anisometropic amblyopic eye. It has been proposed that the efferent accommodative dysfunction may be a fundamental and causative factor in anisometropic amblyopia. A reduced visual acuity for near over that for distance was found in 17 [34%] patients and in 11 out of these the near vision improved after an addition of +3.0D sph. When a reduced visual acuity for near, was obtained it was difficult to determine whether the visual afferent system (due to insufficient visual input), or the accommodation efferent mechanism was responsible. However an improvement in corrected near vision by addition of +3.0D sph. suggested an accommodative dysfunction. In patients with reduced visual acuity for near over that for distance, not only was the final visual outcome poor but also the onset of visual improvement in response to amblyopia therapy was delayed. PMID- 1452282 TI - Emergency surgery in orbital trauma: a neurosurgical view. AB - This study is an analysis of five cases of orbital trauma causing proptosis, paralysis of extraocular muscles with or without associated visual failure. All the cases were treated by a Neurosurgical team. Either a frontal craniotomy or a lateral orbitotomy was performed. Plain X-rays of the skull and Computerised Tomography (C.T. Scanning) were the main investigations. Results were encouraging both functionally and cosmetically. Early diagnosis and an aggressive approach to orbital decompression can achieve good results. PMID- 1452283 TI - Conjunctival and corneal peroxidases in vitamin A deficiency. AB - Xerophthalmia is a commonly encountered nutritional disorder that affects the growing population of the world. Conjunctival and corneal epithelial cells contain peroxidase enzyme. In experimentally induced Vitamin A deficiency conjunctival and corneal peroxidases are markedly lowered indicating direct or indirect relation of Vitamin A to epithelial functional integrity. PMID- 1452284 TI - A clinico-investigative profile in Graves' ophthalmopathy. AB - A clinico-investigative profile was studied in 30 patients with Graves' Ophthalmopathy (GO) (15 each with early and late). In accordance to the thyroid status 63.3% of patients were hyperthyroid and 36.7% euthyroid. There was slight female preponderence, with ratio being 1.5:1. Exophthalmometric readings were significantly high in GO patients as compared to controls. However, no significant diagnostic role of postural exophthalmometry was seen. Positional tonometery may have respectable place among the tests for early diagnosis of GO; however, it could not differentiate between hyperthyroid and euthyroid cases. Further the role of ultrasonography, if available could not be overemphasized. PMID- 1452285 TI - Spontaneous extrusion of cysticercosis: report of three cases. AB - We report three cases of spontaneous extrusion of cysticercosis. In two cases, it got extruded from the orbit and in one case from the subconjunctival space. Extrusion of cysticercosis was associated with improvement in clinical signs and symptoms. PMID- 1452286 TI - Ocular motility disturbances (Duane retraction syndrome and double elevator palsy) with congenital heart disease, a rare association with Goldenhar syndrome- a case report. AB - This report is a case of a 4 year old male child who was admitted for meningitis. On clinical examination he was diagnosed as a case of oculo-suriculo-vertebral dysplasia with congenital heart disease, i.e., tetralogy of Fallots besides his presenting picture of meningitis. During his ophthalmic checkup for the conspicuous presence of epibulbar dermoid, he was discovered to have upper lid coloboma, double elevator palsy, and Grade 1 Duane retraction syndrome in his right eye while the pathognomic feature, a dermolipoma, was present in the left eye. The oculo-auriculo-vertebral dysplasia, as described by Goldenhar, is a disease complex of structures developed from the Ist and IInd branchial arch. The important feature of this case is the bilateral involvement of the disease complex over and above the presence of ocular motility disorders--Duane retraction syndrome and double elevator palsy. PMID- 1452287 TI - Bilateral optic nerve infarction following acute systemic hypotension and anemia- a case report. AB - Presented here are case reports of two patients who became completely blind in both eyes following acute systemic hypotension - in one following bouts of vomiting and in the other after repeated gastrointestinal bleeding. Both patients had severe degree of anemia. There were no other risk factors for vascular disease such as arteriosclerosis or vasculitis. PMID- 1452288 TI - Pharmacology of smooth muscle cell replication. AB - The suggestion that smooth muscle cell proliferation contributes to hypertension, atherosclerosis, and restenosis after angioplasty has led to a growing interest in the use of drugs to inhibit this process. This review summarizes pharmacological studies of smooth muscle cell proliferation in vitro and in vivo and identifies specific mediators of proliferation that are implicated by drugs binding with high affinity to enzymes or receptors. PMID- 1452289 TI - Role of angiotensin subtype 2 receptor in neointima formation after vascular injury. AB - The role of angiotensin receptor subtypes 1 and 2 was assessed on neointima formation after injury in rat carotid artery. The effects of angiotensin converting enzyme inhibition by perindopril (3 mg.kg-1 x day-1 p.o.) and selective blockade of angiotensin subtype 1 receptors by DuP 753 (5 and 30 mg.kg 1 x day-1 p.o.) were compared on proliferative response to balloon injury. In rats treated 6 days before and for 14 days after injury, perindopril significantly reduced (-76%, p < 0.01) myointimal hyperplasia. In contrast, DuP 753 at 5 mg.kg-1 x day-1 did not modify the hyperplastic response to balloon catheterization. Only at 30 mg.kg-1 x day-1 was DuP 753 able to reduce neointima formation (-47%, p < 0.05). This dose was equipotent to perindopril on the renin angiotensin system as assessed by the pressor response to angiotensin II and angiotensin I. Therefore, blockade of subtype 1 receptors was a less effective means of suppression of myointimal growth than angiotensin converting enzyme inhibition, suggesting that another angiotensin receptor subtype or converting enzyme substrates are involved in this process. For the determination of whether angiotensin subtype 2 receptors were implicated, the specific subtype 2 receptor antagonist CGP 42112A (1 mg.kg-1 x day-1) was continuously infused perivascularly for 14 days in the vicinity of the injured carotid artery. CGP 42112A was as effective in preventing neointima formation as perindopril (-73%, p < 0.01, versus -76%, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452290 TI - Receptor-mediated effects of angiotensin II on growth of vascular smooth muscle cells from spontaneously hypertensive rats. AB - This study examines the effects of angiotensin II on hypertrophy and proliferation of aortic smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats and the receptor subtypes mediating these effects. In quiescent confluent cells, angiotensin II induced a dose-dependent increase in thymidine and leucine incorporation without stimulating cell proliferation. In nonconfluent cells, angiotensin II stimulated cell proliferation only in combination with a submaximal concentration of fetal calf serum. These effects were enhanced in cells from spontaneously hypertensive rats compared with Wistar-Kyoto rats. The effects of angiotensin II could be blocked by the AT1 receptor antagonist DuP 753 but not by the AT2 receptor ligand PD 123177. In receptor binding studies with cells derived from both rat strains, AT1-typical binding was observed. These data show that the angiotensin II receptors present in vascular smooth muscle cells in culture from both rat strains are of the AT1 receptor subtype. This receptor subtype appears to mediate vascular smooth muscle cell hypertrophy and proliferation as well as vasoconstriction. Although no difference in the receptor profile was detectable between the two rat strains, the affinity for the ligands to the receptor and the receptor density tended to be greater in cells from spontaneously hypertensive rats than in cells from Wistar-Kyoto rats. These results may partly explain the greater hypotensive response to angiotensin II receptor blockade in spontaneously hypertensive rats than in Wistar-Kyoto rats, although both rat strains have the same plasma concentrations of angiotensin II. PMID- 1452291 TI - Blocking hypothalamic AT1 receptors lowers blood pressure in salt-sensitive rats. AB - Previous studies from our laboratory have shown that microinjection of DuP 753 (2 n-butyl-4-chloro-5-(hydroxymethyl)-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4 yl]methyl]imidazole, potassium salt), a highly selective nonpeptide antagonist of type 1 angiotensin II receptors, into the anterior hypothalamic area produces a dose-related depressor response in salt-sensitive spontaneously hypertensive rats fed a basal (1%) salt diet. The current study tested the hypothesis that the depressor response to anterior hypothalamic type 1 angiotensin II receptor blockade with DuP 753 or its metabolite EXP 3174 is enhanced by high (8%) salt feeding in this model. DuP 753 or EXP 3174 (40 micrograms in 100 nl artificial cerebrospinal fluid vehicle) or vehicle alone was microinjected into the anterior hypothalamic area of conscious salt-sensitive spontaneously hypertensive and Wistar-Kyoto rats that had been fed 1% or 8% salt diets for 3 weeks. Both DuP 753 and EXP 3174 caused significant decreases in mean arterial pressure in spontaneously hypertensive but not in Wistar-Kyoto rats fed either diet. The magnitude and duration of the depressor responses to DuP 753 and EXP 3174 were significantly greater in the 8% salt-fed spontaneously hypertensive rats than in 1% salt-fed rats. Vehicle injections had no effect on blood pressure in either strain-diet group. Microinjection of angiotensin II (2 micrograms in 100 nl artificial cerebrospinal fluid vehicle) into the anterior hypothalamic area caused significant pressor and bradycardiac responses in all strain-diet groups; dietary salt supplementation enhanced these effects in salt-sensitive spontaneously hypertensive rats but not in Wistar-Kyoto rats. These responses were blocked by pretreatment with EXP 3174.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452292 TI - Discovery of a well-absorbed, efficacious renin inhibitor, A-74273. AB - The development of orally active renin inhibitors has been plagued by limited bioavailability in animals and humans. A-74273 is a novel, potent nonpeptide inhibitor of human renin (IC50 = 3.1 nM). This compound was absorbed into the portal and systemic circulations of anesthetized rats, ferrets, monkeys, and dogs after intraduodenal dosing. This favorable pattern also was observed after oral dosing in conscious animals, except in monkeys. Hepatic extraction of A-74273 was more efficient in rats and monkeys than in dogs or ferrets. A-74273 modestly inhibits dog renin, and when given orally as the base (0, 0.3, 1, 3, 10, and 30 mg/kg; n = 8 per dose) to conscious, salt-depleted dogs it induced dose-related reductions in mean arterial pressure and plasma renin activity. Peak falls in mean arterial pressure from normotensive baselines were -14 +/- 1, -26 +/- 3, and -44 +/- 3 mm Hg for the 3, 10, and 30 mg/kg groups, respectively (p < 0.05). Baseline plasma renin activity values (10.9 +/- 1.1-12.7 +/- 1.1 ng angiotensin I/ml/hr) were maximally inhibited, ranging from 43 +/- 8% at 0.3 mg/kg to 98 +/- 1% at 30 mg/kg. Bioavailability in this model was estimated to be 54 +/- 13% when plasma drug levels were determined by a renin inhibitory activity assay, but bioavailability was lower when compared with high-performance liquid chromatographic analysis of A-74273. This discrepancy was accounted for by the identification of structurally similar metabolites that are as active as the parent drug against human renin but much less potent against dog renin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452293 TI - Molecular determinants of human prorenin processing. AB - In humans, active renin is generated by the removal of a 43-amino acid prosegment from the zymogen prorenin. This cleavage event is highly specific, occurring at only one of the seven pairs of basic amino acids in the body of preprorenin. This cleavage site selectivity is also displayed by a number of other proteases in vitro and in mouse pituitary AtT-20 cells transfected with a human preprorenin expression vector, suggesting that specificity of cleavage is directed in part by the primary sequence, the higher order structure, or both of prorenin itself. To test this hypothesis, single amino acid mutations were introduced in the region of human preprorenin surrounding the natural cleavage site, and the resultant recombinant proteins were expressed in cultured Chinese hamster ovary and AtT-20 cells. The results suggest that amino acids in addition to the pair of basic amino acids surrounding the cleavage site affect the ability of both trypsin and the endogenous AtT-20 processing enzyme to cleave prorenin. Notably, although a proline at position -4 is essential for processing of prorenin in AtT-20 cells and is correlated with predicted formation of a beta-turn at this position, site directed mutations suggest that this structural feature in addition to a pair of basic amino acids is not sufficient to lead to proteolytic activation of prorenin. Displacement of sequences surrounding the cleavage site to a position 10 amino acids toward the amino terminus led to partial processing of a mutated prorenin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452294 TI - Non-modulation as an intermediate phenotype in essential hypertension. AB - Non-modulation is a trait characterized by abnormal angiotensin-mediated control of aldosterone release and the renal blood supply. To determine whether non modulation defines a specific subgroup of the hypertensive population and its utility as an intermediate phenotype, we have studied the distribution of this quantitative trait, whether its features are reproducible on repeated testing, and whether there is concordance of its multiple features. Essential hypertensive patients (224) and normotensive subjects (119) received an infusion of angiotensin II (Ang II) at 3 ng.kg-1.min-1 for 30-45 minutes. p-Aminohippurate (PAH) clearance was assessed as an index of renal plasma flow while the subjects were on a 200 meq sodium diet; plasma aldosterone levels were measured while the subjects were on a 10 meq sodium diet. In 54 subjects, diuretic-induced volume depletion superimposed on a low salt diet was substituted for the Ang II infusion. The results of each study were submitted to maximum likelihood analysis to assess bimodality. In response to both diuretic-induced volume depletion (p < 0.000023) and Ang II infusion (p < 0.0009), aldosterone responses were bimodally distributed in the essential hypertensive but not in the normotensive subjects, suggesting that this trait identifies a discrete subgroup. In the 59 subjects who had both an adrenal and renal study, 50 (85%) were concordant. Finally, in 27 subjects studied two to six times over a span of 1-60 months, the intraclass correlations of the adrenal, PAH, or both responses were highly significant (p values between 0.001 and 0.00007), indicating high reproducibility of results on repeated testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452295 TI - Fasting insulin in relation to subsequent blood pressure changes and hypertension in women. AB - The role of hyperinsulinemia in the development of hypertension is not well understood, particularly insofar as both conditions relate to obesity. The present analysis examines the hypothesis that hyperinsulinemia, independent of obesity, precedes hypertension and natural blood pressure increases in women. The subjects were 50-year-old women from a prospective population study in Gothenburg, Sweden. Fasting insulin levels were determined at baseline (1968 1969) and were evaluated in relation to subsequent hypertension. Blood pressures were measured at the initial physical examination and at the 6- and 12-year follow-up examinations. The first analysis presented here (n = 278) identified incident cases of hypertension during the 12-year follow-up period, whereas the second analysis (n = 219) examined continuous changes in blood pressure. In both analyses, degree, type, and changes in obesity were considered as possible confounding factors. High fasting insulin values were predictive of subsequent incidence of hypertension over the 12-year follow-up period. Subjects with insulin values above the 75th percentile experienced three times more hypertension than did those below the 25th percentile. There was also a significant association between insulin at baseline and increases in diastolic (but not systolic) blood pressure. The positive relations between fasting insulin, on one hand, and diastolic blood pressure changes and hypertension, on the other, could not be explained by confounding effects of body mass index, waist/hip ratio, or weight gain. These findings are consistent with the hypothesis that fasting insulin levels may be one predisposing factor in the etiology of hypertension. PMID- 1452296 TI - Hyperdynamic circulation and the insulin resistance syndrome ("syndrome X"). AB - The insulin resistance syndrome ("syndrome X") consists of hyperinsulinemia, glucose intolerance, dyslipidemia, and hypertension, although the inclusion of hypertension has been challenged. Insulin has biological effects that could produce a hyperdynamic circulation. We therefore postulated that an insulin induced hyperdynamic circulation is an early feature of the insulin resistance syndrome and that this circulatory abnormality leads to later fixed hypertension. The San Antonio Heart Study cohort, a population-based cohort of 3,301 Mexican Americans and 1,857 non-Hispanic whites, was used to define individuals who were hyperdynamic (pulse pressure and heart rate in the upper quartile of their respective distributions), intermediate, and hypodynamic (pulse pressure and heart rate in the bottom quartile). The characteristics of the insulin resistance syndrome were then examined according to these three hemodynamic categories. We also examined the 8-year incidence of hypertension and of type II diabetes according to these hemodynamic categories. A hyperdynamic circulation was associated with statistically significant increases in body mass index (BMI) (p < 0.001), subscapular-to-triceps skinfold ratio (p = 0.042), triglyceride (p = 0.002), 2-hour glucose (p = 0.002), and fasting and 2-hour insulin (p = 0.019 and 0.006). When hemodynamic status was examined separately in lean (BMI < 27 kg/m2) and obese (BMI > or = 27 kg/m2) individuals, the above effects persisted, although they were somewhat attenuated. The odds ratio for the hyperdynamic state as a predictor of future hypertension was 1.66, although this was not statistically significant (p = 0.304). The odds ratio for predicting future type II diabetes was 3.97, which was statistically significant (p = 0.047).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452297 TI - Silent cerebral infarction as a form of hypertensive target organ damage in the brain. AB - The incidence, number, size, and location of silent cerebral infarction on 0.1 T magnetic resonance imaging was investigated in 66 hypertensive patients (63 +/- 9 years old; mean +/- SD) and 42 age-matched normotensive subjects (61 +/- 9 years old) to determine the clinical significance of hypertension in silent cerebral infarction. Cerebrovascular risk factors and the severity of hypertensive changes in other major target organs were also investigated. The incidence of silent infarction in hypertensive patients (47%) tended to be higher than that of normotensive subjects (33%) and increased significantly with advancing age. In hypertensive patients, a significantly higher incidence of silent lesions was noted in patients with hypertensive changes in major target organs (72-73% in patients with organ involvement versus 33-39% in those without). The average number of lesions in hypertensive patients was significantly higher than that in normotensive subjects (6.0 versus 2.1), and the lesions in the hypertensive patients were more frequently detected in the brain areas supplied by perforating arteries than those in normotensive subjects (47% versus 24%). These results clearly demonstrate that silent cerebral infarction is frequently seen in older hypertensive patients, especially when moderate hypertensive changes are noted in major target organs, and suggest that hypertensive arterial changes play a crucial role in the occurrence of silent infarction. PMID- 1452298 TI - Morphology of renal afferent arterioles in spontaneously hypertensive rats. AB - We present a new perfusion technique that allows arteries down to the level of capillaries to be fixed while relaxed and under a known intravascular pressure. Through a catheter inserted into the right renal artery of 12-week-old male spontaneously hypertensive rats (n = 9) and control Wistar-Kyoto rats (n = 11), the kidney vessels were rinsed with human plasma, relaxed by papaverine, and perfused with a casting resin containing microspheres. The microspheres (12 microns) became trapped in the glomeruli of the kidney and, together with a closing of the venous outflow, they caused the flow through the kidney to stop, so that the intravascular pressure was raised to the level of the input perfusion pressure (100 mm Hg). The resin material was allowed to harden, and the kidney was immersion-fixed and prepared for histomorphometrical investigations. This technique made it possible to measure both the structurally determined lumen diameter and the corresponding media thickness under clearly defined conditions. The lumen diameter of afferent arterioles close to the glomeruli showed a 17% reduction in spontaneously hypertensive rats (15.4 +/- 0.6 microns; mean +/- SEM) compared with Wistar-Kyoto rat arterioles (18.5 +/- 0.3 microns, p < 0.001). However, this was not due to media hypertrophy, because media cross-sectional area was smaller (p < 0.001) in spontaneously hypertensive rats (210 +/- 6 microns 2) compared with Wistar-Kyoto rats (274 +/- 16 microns 2). We conclude that the lumen reduction in renal afferent arterioles in spontaneously hypertensive rats is not the result of an encroachment on the lumen by a hypertrophic media. PMID- 1452299 TI - Development of hypertension in animals with reduced total peripheral resistance. AB - The object of the present study was to determine whether deoxycorticosterone acetate (DOCA)-salt hypertension can be produced in rats in the presence of low total peripheral resistance (TPR) induced by long-term administration of minoxidil, a vasodilator. The rats were divided into four groups: sham-control, DOCA-salt, minoxidil, and DOCA-salt with minoxidil. The rats in both DOCA groups had DOCA pellets implanted subcutaneously and were given saline to drink. The rats in both minoxidil groups were given minoxidil (3 mg/day) in the drinking water throughout the experiment. Final measurements, including mean arterial blood pressure, cardiac index, and renal blood flow were made after 4-6 weeks. Flow measurements were made using radioactive microspheres. Cardiac index (ml.min 1.100 g-1) in sham-control rats averaged 18 +/- 2 and was higher in the other groups: 23 +/- 4 (DOCA-salt), 25 +/- 2 (minoxidil), and 30 +/- 2 (DOCA-salt plus minoxidil). Mean arterial pressure (mm Hg) was increased in both DOCA-salt rats (160 +/- 8) and DOCA-salt plus minoxidil rats (153 +/- 5) as compared with sham control (116 +/- 2) and minoxidil (113 +/- 3) rats. There was no significant difference in TPR between the sham-control and DOCA-salt rats, but TPR in minoxidil and DOCA-salt plus minoxidil rats was 30% and 28% lower than that in untreated sham-control and DOCA-salt hypertensive rats, respectively. In contrast, renal vascular resistance was significantly increased in both DOCA-salt groups as compared with non-DOCA-salt groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452300 TI - Twenty-four-hour blood pressure profiles in normotensive sons of hypertensive parents. AB - We investigated whether blood pressures are higher in normotensive offspring of hypertensive parents than in normotensive offspring of normotensive parents outside the physician's office and, if so, whether these higher blood pressures are dependent on the level of dietary sodium intake. We compared 24-hour ambulatory blood pressure profiles between 11 normotensive sons of two hypertensive parents and 11 normotensive sons of two normotensive parents; profiles were recorded after 1 week of a low sodium diet (10 meq/day) and after 1 week of a high sodium diet (200 meq/day). The sons of hypertensive parents were on average 6 years older than the sons of normotensive parents (47 +/- 5 [SD] versus 41 +/- 4 years, p < 0.05). The shift from low to high sodium diet did not significantly change the magnitude of differences in office or ambulatory blood pressures between the groups (i.e., no group-by-diet interaction); thus, we assessed group effects by contrasting blood pressure means for each group pooled across diets. Age-adjusted office blood pressure was higher in sons of hypertensive parents than in sons of normotensive parents (116 +/- 7/80 +/- 6 versus 111 +/- 7/75 +/- 6 mm Hg; p = 0.020 for systolic and p = 0.003 for diastolic blood pressure).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452301 TI - Sodium-lithium countertransport and probability of hypertension in Caucasians 47 to 89 years old. AB - The objectives of the present study were to determine whether sodium-lithium countertransport contributes to predicting the probability of having hypertension and to determine whether it does so after other predictor traits have been considered. We used logistic regression to model the relation between sodium lithium countertransport and the probability of having hypertension, estimated by the prevalence of hypertension among 172 men and 252 women, aged 47-89 years, from the Caucasian population of Rochester, Minn. When sodium-lithium countertransport was the only predictor trait considered, it made a statistically significant contribution to prediction both in men (model chi(2)1df = 20.50, p < 0.001) and in women (model chi(2)1df = 16.69, p < 0.001). For each standard deviation increase in sodium-lithium counter-transport, the expected odds of having hypertension increased 2.25 times in men (95% confidence interval [CI], 1.44-3.51) and 1.77 times in women (95% CI, 1.32-2.37). When sodium-lithium countertransport was not considered, the other traits identified as predictors were age, body mass index, and plasma apolipoprotein CII and CII squared; plasma apolipoprotein AI was an additional predictor in women but not in men. When sodium-lithium countertransport was added to models that included the other predictors, it improved prediction both in men (increase in model chi(2)1df = 12.29, p < 0.001) and in women (increase in model chi(2)1df = 4.86, p < 0.027). Based on these complete models, when the other predictors remained at their mean values, each standard deviation increase in sodium-lithium countertransport increased the expected odds of having hypertension 2.06 times in men (95% CI, 1.31-3.22) and 1.48 times in women (95% CI, 1.04-2.21). These results establish that sodium-lithium countertransport provides information that is helpful in predicting the probability of having hypertension and is not reflected in other identified predictor traits. PMID- 1452302 TI - Aftereffects of exercise. PMID- 1452303 TI - In search of recognition. PMID- 1452304 TI - Routine hematological values in term newborns. AB - Routine hematological parameters were investigated in 240 term normal neonates, 40 neonates in the first week of life and 49 infants between 3 and 6 months of age. Term normal neonates were selected on the basis of well defined criteria. Cord blood Hb values of 16.2 +/- 1.5 g/dl compared well with some of the recent Indian studies and Caucasian figures. Cord blood hemoglobin was lower in the presence of low maternal hemoglobin and in newborns delivered by Cesarean section. A wide variation existed in the total and differential leucocyte counts, thus limiting the clinical utility of white cell counts in the newborn period. Platelet counts were within the adult normal range. PMID- 1452305 TI - Micro-invasive management of neonatal bilirubinemia. AB - The present study aims at analyzing the suitability of transcutaneous approach and filter paper technique using Minolta Jaundicemeter in the management of neonatal bilirubinemia. I compared serially measured values of Serum Bilirubin Index (SBI) by using filter paper technique and transcutaneous bilirubin index (TcBI) with serum bilirubin level determined by Diazo Method in 100 clinically jaundiced newborns and in 25 neonates at birth. The estimation of TcBI is simple, quick, reliable and non-traumatic to the newborn with no workload on the laboratory and technician. However, different nomograms are to be prepared for different laboratories, as also for the newborns with difference in skin pigmentation, gestational age and after phototherapy. SBI determined by filter paper technique eliminates these limitations. Moreover, the linear correlation was stronger between SBI and Diazo values (r = 0.9343, p < 0.001) in comparison to TcBI with Diazo values (r = 0.9090, p < 0.001). Further SBI readings almost correspond with actual serum bilirubin levels while corresponding TcBI values were much higher especially at higher diazo values. Thus TcBI can be used routinely for the surveillance of neonatal jaundice till it reaches a level corresponding to critical serum bilirubin level at which active management is required. At this point, serum bilirubin level may be confirmed by SBI. PMID- 1452306 TI - Prognostic score for kerosene oil poisoning. AB - Ninety five consecutive children with kerosene oil poisoning were studied, the first 70 retrospectively (internal group) and the rest 25, prospectively (external group) over a period of 3 years and 8 months. Based on clinical features and severity of illness in initial 70 cases, a weighted scoring system to determine the outcome was evolved. This included: (i) fever--absent 0, present 1; (ii) severe malnutrition--absent 0, present 1; (iii) respiratory distress- absent 0, present 2, with cyanosis 4; and (iv) neurological symptoms--absent 0, present 2, with convulsions 4. The scores ranged from 0 to 10 in the internal group. Using discriminate function analysis, a score of 4 or more was found to be associated with prolonged hospital stay and complications. The risk of dying increased if the score was equal to or more than 8. The predictive value of the score was 85.7%. For validation, this scoring was applied to the external group as well and 84% of cases could be correctly predicted. PMID- 1452307 TI - Congenital heart disease in Down syndrome: an echocardiographic study. AB - We evaluated the utility of echocardiography in assessing the frequency and nature of cardiac malformations in children with Down syndrome. Fifty cases of chromosomally proven Down syndrome were studied. A physical examination, electro cardiogram, radiograph of chest and two-dimensional echocardiography was performed on all patients. Twenty-two (44%) children had heart diseases. Endocardial-cushion-defect was the commonest anomaly, followed by ventricular septal defect. Three children with heart disease were asymptomatic and had normal X-ray films of chest and ECGs. The prevalence and specific type of congenital heart disease in this study is comparable to the studies using invasive means for diagnosis. The study further suggests that clinical examination of the cardiovascular system alone may not be sufficient in detecting heart disease. Two dimensional echocardiography offers an excellent non-invasive tool for diagnosing cardiac malformations in Down syndrome. PMID- 1452308 TI - A study of hepatitis B and C prevalence and liver function in multiply transfused thalassemic and their parents. AB - A series of clinics were conducted in Delhi, India, in January, 1990. Of 54 patients with beta thalassemia major (mean age 7.6 years), 11.1% (6 out of 54) tested positive for antibodies to hepatitis C virus (anti HCV antibodies) and 66.6% (36 out of 54) showed evidence of hepatitis B virus (HBV) infection. Only 7.4% (4 out of 54) were hepatitis B surface antigen (HBsAg) positive. Of their parents, 2.2% (2 out of 90) tested positive for anti HCV antibodies, 28.9% (26 out of 90) showed evidence of previous HBV infection and 11.1% (10 out of 90) were HBsAg positive. We argue that HCV constitutes a greater long term threat than HBV in these patients due to the higher incidence of chronic liver disease. We would advocate the introduction of HCV screening of donated blood as well as reinforcing the importance of HBV screening and immunization. PMID- 1452309 TI - Shigellosis in children: a prospective hospital based study. AB - From 1985 to 1988, fecal samples of 950 hospitalized children suffering from diarrhea or dysentery were screened for Shigella species using standard methods. Shigella species were isolated as sole pathogen from 192 (20.2%) cases and S. flexneri type 2 was the predominant serotype. Shigella infection was prevalent throughout the year with high isolation rate during the summer and early monsoon months. Shigella strains isolated during the period were resistant to most of the commonly used drugs for the treatment of shigellosis. Nearly 16% of the Shigella strains were also resistant to nalidixic acid. Presence of blood and mucus in stools (dysentery) was the common clinical presentation of shigellosis cases. Malnutrition was associated with longer duration of illness. High cases fatality rate (16.7%) was observed among hospitalized children infected with Shigella. PMID- 1452310 TI - Osteoarticular tuberculosis in children. AB - One hundred and four cases of osteoarticular tuberculosis were studied. There were 74 boys (71.2%) and 30 girls (28.8%). The mean age at the onset of symptoms was 7.3 years, ranging from 9 months to 18 years. Seventy four cases (71%) reported 3 months after onset of symptoms. The spine was the commonest site involved (43%) followed by hip (14.9%) and knee joints (10.3%). Evidence of active or inactive pulmonary tuberculosis was found in 16.2%. All cases were treated by three drug regimen of rifampicin, isoniazid and ethambutol; rifampicin was discontinued after 6 months, ethambutol after 12-14 months. In 12 cases (11.5%) isoniazid was continued for 18 months. Along with chemotherapy suitable braces, splints, tractions, exercises and other form of physical therapy produced satisfactory results. Seventy eight patients (75%) showed clinical and radiological improvement with one year of treatment. The follow up period ranged between 4 months to 24 months with an average of 17 months. Children because of capacity to grow, showed progressive deformity in knee in 3 cases (2.8%), hip in 98 cases (8.6%), shortening of limbs in 14 cases (13.4%) and kyphosis in 13 cases (12.5%). PMID- 1452311 TI - Colonoscopically reduced intussusception and testicular involvement in Henoch Schonlein purpura. PMID- 1452312 TI - Prenatal diagnosis of Bochdalek's type of diaphragmatic hernia. PMID- 1452313 TI - Gastric teratoma revealed by gastrointestinal hemorrhage. PMID- 1452314 TI - Total intestinal anganglionosis. PMID- 1452315 TI - Congenital absence of ribs. PMID- 1452316 TI - Anterior sacral meningocele: an uncommon cause of constipation in early childhood. PMID- 1452317 TI - Melkersson Rosenthal syndrome: oligosymptomatic form. PMID- 1452318 TI - Congenital subclavian artery aneurysm. PMID- 1452319 TI - Starvation--a rare cause of intussusception in preadolescence. PMID- 1452320 TI - Problems in the anesthetic management of Pierre Robin and Treacher Collin syndromes. PMID- 1452321 TI - Incidence of mitral valve prolapse in children. PMID- 1452322 TI - Cerebral symptoms with P. vivax malaria. PMID- 1452323 TI - Assessment of newborn baby's temperature by human touch: a potentially useful primary care strategy. PMID- 1452324 TI - Discarded infant feeding bottle as spacer. PMID- 1452325 TI - Management of hypertensive emergencies. PMID- 1452326 TI - Intrauterine intussusception as a cause of intestinal atresia. PMID- 1452327 TI - Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex. AB - In an effort to prepare pneumococcal (Pn) capsular polysaccharide (Ps) vaccines that would be immunogenic in infants, covalent conjugates were prepared for Pn types 6B, 14, 19F, and 23F. Each Ps type was covalently bound to an outer membrane protein complex from Neisseria meningitidis serogroup B and evaluated for immunogenicity in mice and infant monkeys. The conjugates induced specific anti-Ps antibody responses in mice and in infant rhesus and African green monkeys; a conjugate of 6B and outer membrane protein complex was immunogenic at Ps doses as low as 20 ng. Although low levels of the Pn group-common cell wall polysaccharide were present in all type-specific Ps preparations, anti-cell wall polysaccharide responses induced by covalent conjugates were < 1% of the total anti-Ps response after two doses of vaccine. In contrast, the anti-cell wall polysaccharide response of a noncovalent conjugate represented 41% of the anti-Ps response after two doses. Relative T-cell dependence, a requirement for the human target population of infants less than 18 months old, was demonstrated for all four Pn Ps conjugates in an athymic mouse model. Therefore, these Pn Ps-outer membrane protein complex conjugate vaccines are excellent candidates for evaluation in human infants. PMID- 1452328 TI - Effect of Pasteurella multocida toxin on bone resorption in vitro. AB - Pasteurella multocida toxin (PMT), which is the primary etiologic factor in the pathogenesis of progressive atrophic rhinitis in pigs, was found to stimulate bone resorption in vitro. This stimulation was observed both in cultures of murine calvaria by measuring the release of calcium and of the lysosomal enzyme beta-glucuronidase and in murine long bone cultures by measuring the release of calcium. Both systems showed the same dose response curve, with the maximal effect at a concentration of 5 ng/ml. The effect on calvaria was studied in more detail. PMT increased bone resorption 24 h after its addition and always had to be present to express an effect. Calcitonin was able to inhibit this increase of resorption completely, and inhibitors of prostaglandin synthesis suppressed it partially. Although the data show an effect of PMT on bone tissue, the results do not exclude an action on cells in the nasal cavity, which could indirectly stimulate bone resorption. PMID- 1452329 TI - Protection of neonatal mice from group B streptococcal infection by maternal immunization with beta C protein. AB - Group B streptococci (GBS) cause the majority of cases of neonatal sepsis and meningitis in the United States. Immunization of women of childbearing age is one strategy under consideration for the prevention of neonatal disease. The beta C protein, a 130-kDa antigen present in many clinical isolates of GBS, was purified from GBS by extraction into sodium dodecyl sulfate (SDS)-containing buffer, preparative SDS-polyacrylamide gel electrophoresis, and electroelution. Purified beta C protein antigen (25 micrograms) with Freund's adjuvant was used to immunize rabbits. Rabbits developed enzyme-linked immunosorbent assay titers of > 1:1.6 x 10(6), and sera from immunized rabbits were administered to pregnant mice. Their neonatal pups were then challenged with a strain of GBS expressing beta C protein; 68% of these pups were protected by immune antiserum, whereas no controls were protected (P < 0.001). The immune serum (diluted 1:100) facilitated opsonophagocytic killing of GBS strains expressing the beta C protein but not those that do not express the antigen (mean log kill +/- standard deviation = 0.71 +/- 0.8 log10 CFU for beta+ strains and 0.09 +/- 0.2 for beta- strains; P = 0.02). In subsequent experiments, adult female mice were actively immunized with two doses of 2, 5, or 10 micrograms of beta C protein 2 months prior to mating. One- to two-day-old offspring of these dams were challenged with GBS and were protected in a dose-dependent manner, with 96% survival in the high-dose (10 micrograms) group and 20% survival in a sham-immunized control group (P < 0.001). Thus, active immunization of mice with the GBS beta C protein confers protection against lethal infection with beta+ GBS to their offspring. PMID- 1452331 TI - Phagolysosomes of Coxiella burnetii-infected cell lines maintain an acidic pH during persistent infection. AB - Coxiella burnetii, the agent of Q fever, is an obligate intracellular bacterium that multiples within vacuoles of phagolysosomal origin. Persistently infected cell lines were maintained in continuous culture for months. We studied the pH of the phagolysosomes by using two murine cell lines during early propagation of the bacteria and after establishment of persistent infection. Three strains of C. burnetii were studied because of the purported propensity of each strain to cause acute or chronic disease and to be resistant or susceptible to antibiotics. The pHs were calculated from fluorescence experiments with fluoresceinated dextran as a lysosomal probe. Phagolysosomal vacuoles maintained an acidic pH during a 36 day infection. Minimal variation of the pH occurred over the duration of the experiment with strains that caused either acute or chronic disease. Phagolysosomal pH remained stable for as long as 153 days with the Nine Mile phase II isolate. Thus, neither the course of C. burnetti infection nor the diversity of antibiotic susceptibility of the strains is related to variations in the phagolysosomal pH. PMID- 1452330 TI - Purification and immunological characterization of a major low-molecular-weight lipoprotein from Borrelia burgdorferi. AB - Borrelia burgdorferi resembles gram-negative bacteria in having both cellular and outer membranes. We previously showed that a lipopolysaccharide (LPS)-like material could be extracted from B. burgdorferi with phenol-chloroform-petroleum ether (PCP). The PCP extract of B. burgdorferi exhibited biological activity in several in vitro assays (e.g., mitogenicity, pyrogenicity, and cytokine release). These activities suggested the presence of endotoxin. The PCP extract of B. burgdorferi, however, also contained a small amount of protein. Preliminary studies showed that monoclonal antibody prepared against this protein inhibited the mitogenic activity of the PCP extract toward murine spleen cells. The current study was therefore undertaken to characterize this protein and to establish methods for its separation from the LPS. The PCP-extracted protein consisted of a single, low-molecular-weight lipoprotein (apparent M(r), 10,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) (SDS-PAGE). By protein analysis, it accounted for 2% of the dry weight of defatted cells, thus making it a major constituent of the spirochete. It was purified from the LPS by initial extraction into 10% Triton X-100 followed by immunoaffinity chromatography in the presence of detergent. On removal of the LPS, the purified lipoprotein formed aggregates stable to SDS-PAGE which were detectable on Western blots (immunoblots) probed with either the monoclonal antibody or polyclonal antiserum. From a plot of the aggregate molecular weight versus aggregate size, a monomer molecular weight of 7,500 was obtained. Indirect immunofluorescence with the monoclonal antibody showed that the lipoprotein was exposed at the surface of the spirochete in only a small percentage of cells. The lipoprotein was present in several strains of B. burgdorferi but absent in other Borrelia spp., treponemes, and gram-negative human pathogens, indicating species specificity. PMID- 1452332 TI - Pathogenesis of Providencia alcalifaciens-induced diarrhea. AB - Providencia alcalifaciens is a member of the family Enterobacteriaceae. There are reports that P. alcalifaciens can cause diarrhea, but the mechanism(s) by which it causes diarrhea is known. We studied P. alcalifaciens isolated from a child and two adults with diarrhea for enteropathogenicity. The three isolates did not exhibit any characteristic adherence to cultured HEp-2 cell monolayers, and they did not produce enterotoxins, cytotoxins, or keratoconjunctivitis in the Sereny test. Two isolates invaded cultured HEp-2 cell monolayers, producing localized bacterial clusters and actin condensation. The pattern of actin condensation was different from that produced by enteropathogenic Escherichia coli but similar to that produced by Shigella flexneri. Invasion and actin condensation were poor for the third isolate. Histology of adult rabbit small intestinal loops inoculated with all three isolates revealed bacterial attachment to, penetration of, and microulcer formation on the surface epithelium and hyperemia, edema, and polymorphonuclear cell infiltration of lamina propria. All the isolates produced diarrhea in rabbits with removable intestinal ties, and some of these rabbits developed hindlimb paralysis. Intestinal histology of the rabbits with removable intestinal ties which developed diarrhea showed changes similar to that in adult rabbits on which ileal loop assays had been performed. Transmission electron microscopy of intestinal tissues also confirmed tissue penetration by the isolates. Nerve tissue histology of two rabbits that developed hindlimb paralysis showed focal mononuclear cell infiltration around peripheral nerve sheaths. It is concluded that some strains of P. alcalifaciens are enteropathogenic and that they cause diarrhea by invading the intestinal mucosal epithelium. However, the relevance to human disease of the hindlimb paralysis observed in this animal model is not clear. PMID- 1452333 TI - Relative abilities of distinct isotypes of human major histocompatibility complex class II molecules to bind streptococcal pyrogenic exotoxin types A and B. AB - The relative ability of distinct isotypes of human leukocyte antigen class II molecules to bind streptococcal pyrogenic exotoxins A and B (SPE A and SPE B, respectively) was investigated by a direct-binding assay with 125I-labeled toxin for SPE A and by a functional assay system measuring the accessory cell activity of human leukocyte antigen class II transfectants in toxin-induced T-cell activation for SPE A and SPE B. SPE A binding was observed in L cells transfected with DQw1 genes. By contrast, it was not detected in L cells transfected with DR2, DR4, DPw4 or DP(Cp63) genes. All the transfectants supported SPE-induced interleukin-2 production by human T cells except the DP transfectants for SPE B. Levels of accessory cell activity were low in the DP transfectants induced by stimulation with SPE A and in the DR and DP transfectants induced by SPE B. The results indicate that SPE A and SPE B bind well to DQ molecules, less well to DR molecules, and very weakly to DP molecules. PMID- 1452334 TI - Complement and antibody participation in opsonophagocytosis of type IV and V group B streptococci. AB - Requirements for complement and antibody in neutrophil-mediated killing of serotype IV and V group B streptococci were investigated. Neutrophils from adults were tested in an opsonophagocytic assay with sera from healthy adults, healthy newborns, and hypogammaglobulinemic, agammaglobulinemic, and C4-deficient patients. For all serum sources, the bactericidal index for both serotypes exceeded 84% after 40 min of incubation. Heat inactivation of sera ablated killing. Blockade of neutrophil receptor FcIII effected a maximum of 16% inhibition of opsonophagocytosis, and FcII receptor blockade demonstrated negligible inhibition. When neutrophil complement receptor 1 or 3 blockade was employed, the maximum inhibition detected was 26%. Simultaneous blockade of complement receptors 1 and 3 effected maximum inhibition levels of 25 and 65% for serotypes IV and V, respectively. Blockade of complement receptor 3 and neutrophil receptor FcIII inhibited opsonophagocytosis by 56% for both serotypes. When serum complement concentrations were restricted, neutrophil-mediated killing diminished but was restored by the addition of hyperimmune rabbit antiserum. These findings suggest that complement and antibody are major participants in the opsonophagocytosis of serotypes IV and V group B streptococci. A low prevalence of carriage or mediation of efficient phagocytosis by interactions of neutrophil complement and Fc receptors may contribute to the rarity of human infections caused by these two serotypes. PMID- 1452335 TI - Role of fibrinogen in complement inhibition by streptococcal M protein. AB - M protein, the major virulence factor of group A streptococci, has antiopsonic activity in that it inhibits activation of the alternative complement pathway on the streptococcal surface. Two properties of M protein have been claimed to account for the inhibitory activity, namely, (i) its binding affinity for complement factor H, which is an inhibitor of alternative pathway activation, and (ii) its high binding affinity for fibrinogen. We have recently shown that fibrinogen, like M protein, inhibits alternative pathway activation by possessing binding affinity for factor H. Here we report that fibrinogen effectively competes with factor H for binding to M protein but retains its own binding affinity for factor H. The presence of fibrinogen did not significantly affect alternative pathway inhibition on the streptococcal surface. PMID- 1452336 TI - eNAP-2, a novel cysteine-rich bactericidal peptide from equine leukocytes. AB - We purified a novel cysteine-rich antibiotic peptide, eNAP-2 (M(r), approximately 6,500), from acid extracts of equine neutrophils by sequential gel filtration and reversed-phase high-performance liquid chromatography and determined its partial N-terminal amino acid sequence. Although its cysteine motif distinguished eNAP-2 from all other currently known endogenous antibiotic peptides, including defensins and granulins, it showed substantial sequence similarity to WDNM1, a putative member of the four-disulfide-core protein family that also includes animal and human antiproteases, snake venom neurotoxins, and rat and mouse whey proteins. The antibacterial properties of eNAP-2 were tested against several equine uterine pathogens, namely, Streptococcus zooepidemicus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Killing of S. zooepidemicus was very efficient, as evidenced by a 94% decrease in numbers of CFU per milliliter after exposure to 100 micrograms of eNAP-2 per ml (approximately 15 microM) for 2 h. Exposure of E. coli and P. aeruginosa to 200 micrograms of eNAP 2 per ml for 2 h resulted in 90.2 and 77.6% reduction, respectively, in the numbers of CFU per milliliter. Bacteriostasis, without bactericidal activity, occurred after K. pneumoniae was incubated with 200 micrograms of eNAP-2 per ml. Additional studies will be required in other species and cell types to determine whether eNAP-2 is restricted to equine neutrophils or is the index member of a larger family of endogenous antibiotics. PMID- 1452337 TI - Characterization of a polysaccharide capsular antigen of septicemic Escherichia coli O115:K "V165" :F165 and evaluation of its role in pathogenicity. AB - Escherichia coli strains of serogroup O115:K(-):F165 have been associated with septicemia in calves and piglets. These strains express a capsular antigen referred to as K"V165" which inhibits agglutination of the O antigen by anti-O115 serum. We used hybrid transposon TnphoA mutants M48, 18b, and 2, and a spontaneous O-agglutinable mutant, 5131a, to evaluate the role of K"V165" in the pathogenicity of E. coli O115. Mutant M48 was as resistant to 90% rabbit serum and as virulent in day-old chickens as the parent strain 5131, mutants 18b and 5131a were less resistant to serum and less virulent in chickens, and mutant 2 was serum sensitive and avirulent. Analysis of outer membrane protein and lipopolysaccharide profiles failed to show any difference between the transposon mutants and the parent strain. In contrast, the spontaneous O-agglutinable mutant showed additional bands in the 16-kDa region of the polysaccharide ladder-like pattern. Mutants 2 and 5131a produced significantly less K"V165" capsular antigen than the parent strain, as demonstrated by a competitive enzyme-linked immunosorbent assay with adsorbed anti-K"V165" serum. In addition, electron microscopic analysis revealed that mutants 2 and 5131a had lost the capsular layer observed in the parent strain after fixation with glutaraldehyde-lysine. This capsule contained carbohydrate compounds and resembled an O-antigen capsule since it prevented O-antigen agglutination before the bacteria were heated at 100 degrees C and induced bacterial serum resistance. The capsule-defective mutants colonized the intestinal epithelium of experimentally infected gnotobiotic pigs but failed to induce clinical signs of septicemia. We concluded that E. coli strains of serogroup O115 expressed a polysaccharide capsular antigen which induced serum resistance and consequently contributed to the pathogenicity of the bacteria. PMID- 1452338 TI - Proteins with molecular masses of 25 to 40 kilodaltons elicit optimal protective responses against Plasmodium chabaudi adami infection. AB - The presence of the CD4+ T cell has been shown to be crucial for resolution of acute infection in the Plasmodium chabaudi adami murine malaria model. This model is, therefore, suitable for the isolation of malaria antigens that are capable of activating protective T cells. In light of this, we set out to identify P. chabaudi adami molecules that activate protective responses in this model. Denatured P. chabaudi adami proteins were isolated by continuous-flow electrophoresis on the basis of their apparent molecular masses and then sequentially assessed for the ability to protect mice in immunization experiments. We report here that low-molecular-mass P. chabaudi adami polypeptides in the range from 25 to 40 kDa are most effective at immunizing mice against a challenge infection with viable P. chabaudi adami. The method used to obtain these proteins could also be applied to identify molecules that activate protective cell-mediated responses in other infectious disease models. PMID- 1452339 TI - Construction of a diphtheria toxin A fragment-C180 peptide fusion protein which elicits a neutralizing antibody response against diphtheria toxin and pertussis toxin. AB - A genetically engineered gene fusion was constructed which encoded a nontoxic derivative of the A fragment of diphtheria toxin joined to the C180 peptide of the S1 subunit of pertussis toxin. The product of this gene fusion, termed the DTA-C180 protein, was purified from the periplasm of Escherichia coli to approximately 80% purity. The DTA-C180 protein possessed an apparent molecular weight of 43,000 by reduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The DTA-C180 protein was cleaved into two tryptic peptides, which migrated with apparent molecular weights of approximately 22,000. One tryptic peptide reacted with diphtheria antitoxin, while the other tryptic peptide reacted with anti-C180 peptide immunoglobulin G. The DTA-C180 protein did not inhibit protein synthesis or stimulate clustering morphology in Chinese hamster ovary cells. The DTA-C180 protein elicited an immune response, in guinea pigs, against both the DTA and C180 peptide components of the fusion protein, with alum being a more efficient adjuvant than Freund's adjuvant for eliciting neutralization titers. Neutralization titers elicited by DTA-C180 protein were weaker than those elicited by diphtheria toxoid and pertussis toxin 9K/129G, a genetically engineered double mutant of pertussis toxin. Three doses of DTA-C180 protein yielded a neutralization titer of 1/750 against pertussis toxin in Chinese hamster ovary cells and a neutralization titer of 1/50 against diphtheria toxin in Vero cells. This is the first report of a protein derived from a recombinant S1 subunit that elicits a neutralizing titer against pertussis toxin. PMID- 1452340 TI - Differences in the binding specificities of Pseudomonas aeruginosa M35 and Escherichia coli C600 for lipid-linked oligosaccharides with lactose-related core regions. AB - Membrane glycolipids contain the lactose sequence (galactose linked to glucose), and the oligosaccharide is variously extended such that there is a cell-type specific repertoire. In this study, binding of Pseudomonas aeruginosa M35 to lipid-linked lactose (Gal beta 1-4Glc [structure 1]), lacto-N-neotetraose (Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc [structure 2]), lacto-N-tetraose (Gal beta 1-3GlcNAc beta 1-3Gal beta 1-4Glc [structure 3]), and asialo GM1 (Gal beta 1 3GalNAc beta 1-4Gal beta 1-4Glc [structure 4]) was evaluated and compared with binding of Escherichia coli C600 to these compounds. Oligosaccharides were linked to the lipid phosphatidylethanolamine dipalmitoate, and the resulting neoglycolipids were resolved on thin-layer chromatograms or coated onto plastic microtiter wells. Lipid-linked structures 1 to 4 were bound by P. aeruginosa and E. coli in the chromatogram assay, but only structure 4 was bound in the microtiter well assay. As shown previously for E. coli binding to lipid-linked structures 1 to 3, binding to lipid-linked structure 4 was not inhibited with oligosaccharide, indicating a requirement for lipid and oligosaccharide. With few exceptions, sialylation and fucosylation of structures 1 to 4 resulted in impaired or abolished binding. Comparisons of binding intensities in the chromatogram assay indicated that recognition by P. aeruginosa and recognition by E. coli are not identical. Presence of the additional disaccharide unit, as in structure 2, resulted in enhanced binding of P. aeruginosa but diminished binding of E. coli relative to lactose binding; fucosylation at galactose of lactose resulted in markedly diminished binding of P. aeruginosa only. In the microtiter well assay, binding of E. coli to asialo GM1 was much weaker than P. aeruginosa binding. The saccharide-plus-lipid-dependent adhesion may be an important factor in increased susceptibility to infection of epithelia already damaged by microbial and chemical agents; the differing strengths of adhesion to the structural variants may relate to tissue tropism. PMID- 1452341 TI - Interaction of pertussis toxin with human T lymphocytes. AB - The binding of pertussis toxin (PT) to the human T-cell line Jurkat was examined by using flow cytometry. Fluorescein isothiocyanate (FITC)-labeled PT bound rapidly to the cells in a specific manner as determined by blocking experiments with unlabeled toxin, B oligomer, and the S2-S4 and S3-S4 dimers. Monoclonal antibodies against the S3 subunit of the toxin also significantly inhibited the binding of FITC-PT. Sialidase treatment of the cells resulted in decreased binding of FITC-PT, indicating that sialic acid residues are involved in the binding process. In addition, we studied the effect of PT binding on the expression of cell surface molecules. On binding of PT to the cell surface, a rapid down-regulation of the T-cell receptor (TCR)-CD3 complex was observed. The modulation of the TCR-CD3 complex was independent of the toxin's enzymatic activity, as the B oligomer and a nonenzymatic toxin mutant induced modulation comparable to that caused by the native holotoxin. Isolated dimers did not cause down-regulation. Stimulation of the TCR-CD3 complex, leading to reduced cell surface expression of this complex, provides a possible explanation for the second messenger production associated with the interaction of PT or B oligomer with T lymphocytes. We therefore conclude that PT activates T cells by divalent binding to the TCR-CD3 complex itself or by binding a structure closely associated with it. PMID- 1452342 TI - Identification of p60 antibodies in human sera and presentation of this listerial antigen on the surface of attenuated salmonellae by the HlyB-HlyD secretion system. AB - Antibodies directed against the major secreted protein of Listeria monocytogenes, termed p60, were found more frequently than antilisteriolysin antibodies in sera of listeriosis patients. Anti-p60 antibodies were also identified in all tested sera from healthy individuals. To test whether p60 provides protection against L. monocytogenes, we constructed an attenuated Salmonella typhimurium aroA strain which secretes p60 via the Escherichia coli hemolysin secretion pathway. Application of this Salmonella strain to BALB/c mice prior to an L. monocytogenes infection induced p60 antibodies in these mice and led to a significantly reduced number of viable bacteria in the spleen compared with that in control animals which were primed with the S. typhimurium aroA strain alone. PMID- 1452343 TI - Demonstration and partial characterization of antigens of Rickettsia rhipicephali that induce cross-reactive cellular and humoral immune responses to Rickettsia rickettsii. AB - The relatively unrelated spotted fever group rickettsia Rickettsia rhipicephali conferred on guinea pigs protective immunity against challenge with virulent R. rickettsii. Immunity was conferred at all doses of R. rhipicephali used in the study. Because of the serologic unrelatedness of these two rickettsiae, determined by the use of microimmunofluorescence and other serological assays, further studies were performed to define the nature of the immune response elicited by R. rhipicephali and the characteristics of the rickettsial antigens that evoke cross-reactive antibody responses. Animals immune to R. rhipicephali tested at the time of challenge showed a complete cross-reactive lymphocyte proliferative response to rickettsial antigens prepared from each species. In fact, spleen cells from R. rhipicephali-immune animals responded better to R. rickettsii antigens than to homologous immunizing antigens. Serum samples were obtained from R. rhipicephali-infected animals at various times after infection and tested by the use of Western immunoblot assay for antibodies that were cross reactive with antigens of R. rickettsii. By 10 days after infection with R. rhipicephali, antibodies to antigens of both species were noted, and by 37 days after infection, sera from immune animals showed strong reactivity to antigens of R. rhipicephali with apparent molecular masses of 107 and 151 kDa. The cross reactive antibody response to antigens of R. rickettsii was relatively strong and involved predominantly the rOmpB protein and the rickettsial lipopolysaccharide. These findings establish the presence of T-cell-dependent epitopes associated with antigens of R. rhipicephali, which confer protective immunity against challenge with R. rickettsii. Results of Western immunoblot assays support the contention that the R. rickettsii rOmpB surface antigen contains important protective epitopes. PMID- 1452344 TI - Endogenous tumor necrosis factor alpha is required for enhanced antimicrobial activity against Toxoplasma gondii and Listeria monocytogenes in recombinant gamma interferon-treated mice. AB - In vitro studies have shown that macrophages stimulated with recombinant gamma interferon (rIFN-gamma) produce tumor necrosis factor alpha (TNF-alpha), which in an autocrine fashion activates these cells. The aim of the present study was to determine whether endogenously formed TNF-alpha also is required for rIFN-gamma induced macrophage activation and enhanced antimicrobial activity in vivo. After an intraperitoneal injection of rIFN-gamma into CBA/J mice, their peritoneal macrophages released enhanced amounts of NO2- and inhibited the intracellular proliferation of Toxoplasma gondii. Injection of neutralizing antibodies against TNF-alpha simultaneously with the rIFN-gamma completely inhibited both the release of NO2- by macrophages and their toxoplasmastatic activity. Similar results were observed after intraperitoneal injection of a competitive inhibitor of L-arginine, NG-monomethyl-L-arginine, together with rIFN-gamma, demonstrating that in vivo L-arginine-derived reactive nitrogen intermediates are essential for the induction of toxoplasmastatic activity. Intravenous injection of rIFN-gamma inhibited the growth of Listeria monocytogenes in the livers and spleens of mice; this effect was abrogated by antibodies against TNF-alpha. Intravenous injection of a large dose of rTNF-alpha resulted in a decrease in the number of bacteria in the liver and spleen, but an injection of rIFN-gamma and rTNF-alpha did not result in enhanced inhibition of the proliferation of L. monocytogenes. Together, the results of the present study are the first to demonstrate that endogenous TNF alpha is required in vivo for the expression of macrophage activation with respect to the release of reactive nitrogen intermediates and toxoplasmastatic activity and for enhanced listericidal activity in the livers and spleens of mice stimulated with rIFN-gamma. PMID- 1452345 TI - Expression of protein F, the fibronectin-binding protein of Streptococcus pyogenes JRS4, in heterologous streptococcal and enterococcal strains promotes their adherence to respiratory epithelial cells. AB - In a previous study we reported the identification of protein F, a fibronectin binding protein that was essential to the ability of Streptococcus pyogenes JRS4 to adhere to respiratory epithelial cells (E. Hanski and M. Caparon, Proc. Natl. Acad. Sci. USA, 89:6172-6176, 1992). To further evaluate the role of protein F in the adherence of the group A streptococci, we screened other group A streptococcal strains, including six recent clinical isolates, and one strain of Enterococcus faecalis for their capacity to bind fibronectin and for the presence of the gene encoding protein F (prtF). Seven of eight group A streptococcal strains analyzed, including all recent clinical isolates, both bound fibronectin at high affinity and contained DNA sequences that hybridized with a prtF-specific probe. One group A streptococcal isolate and the strain of E. faecalis examined neither contained a prtF-related gene nor bound fibronectin. These two strains also could not efficiently adhere to respiratory epithelial cells. However, upon the introduction of the cloned prtF gene, both of these strains gained the capacity to bind fibronectin and to adhere to respiratory epithelial cells. These results suggest that protein F is an important adhesin, which may have a general role in the virulence of the group A streptococci. PMID- 1452346 TI - The arginine-dependent cytolytic mechanism plays a role in destruction of Naegleria fowleri amoebae by activated macrophages. AB - Mouse peritoneal macrophages activated by different immunomodulators (Mycobacterium bovis bacillus Calmette-Guerin or Propionibacterium acnes) destroy Naegleria fowleri amoebae by a contact-dependent process and by soluble cytolytic molecules secreted by macrophages in response to lipopolysaccharide. The goal of this study was to determine whether the arginine-dependent cytolytic mechanism which results in the production of nitric oxide from arginine by activated macrophages destroys the amoebae. Amoebicidal activity of activated macrophages was determined by coculturing macrophages with N. fowleri amoebae radiolabeled with 3H-uridine. The percent specific release of radiolabel was used as an index of cytolysis of the amoebae. The inhibitors NG-monomethyl-L-arginine and arginase were used to determine whether the arginine pathway was a major effector mechanism responsible for amoebicidal activity of activated macrophages. Both the arginine analog NG-monomethyl-L-arginine and arginase, which breaks down arginine, decreased macrophage amoebicidal activity. Addition of arginine to arginine-free medium restores amoebicidal activity to activated macrophage cultures. These results demonstrate that the arginine pathway is an important mechanism for the destruction of susceptible N. fowleri amoebae. PMID- 1452348 TI - Lack of vessel wall elastolysis in human invasive pulmonary aspergillosis. AB - In experimental studies, the apparent ability of Aspergillus fumigatus isolates to produce elastase in agar plates correlates with their ability to cause invasive pulmonary aspergillosis in mice pretreated with cortisone. Thus, elastase production may govern the pathogenicity of particular isolates. If this is so, then disruption of the elastic layers within blood vessel walls in invasive aspergillosis would be expected. To test this hypothesis, tissue blocks were prepared from nine patients with invasive pulmonary aspergillosis. Separate but immediately adjacent histological sections were stained by the Grocott and periodic acid-Schiff methods for fungal hyphae and by the elastic van Gieson technique for elastic tissue. Comparison of those segments of vessel walls infiltrated by hyphae with those not infiltrated by hyphae showed no overall loss of elastic tissue. Material from five of the cases was also stained with an unconventional combination of histochemical stains, allowing accurate identification of both fungal hyphae and elastic laminae in the same histological sections. The results showed no more disruption of elastic laminae than would be expected from simple physical displacement of elastic laminae. We conclude that if elastolysis contributes at all to invasion of vessel walls by aspergilli, then it seems to be very localized and/or transient. PMID- 1452347 TI - Characterization of a > 900,000-M(r) Cryptosporidium parvum sporozoite glycoprotein recognized by protective hyperimmune bovine colostral immunoglobulin. AB - Cryptosporidium parvum, a zoonotic Apicomplexan pathogen, causes profound diarrhea, malnutrition, and dehydration in patients with AIDS. A less severe, self-limited disease occurs in immunocompetent individuals, particularly children, animal handlers, and residents of the developing world. Very little is known about the biology of the organism, the pathophysiology of the disease process, or the mechanism of protective immunity. There is no effective therapy for cryptosporidiosis, but hyperimmune bovine colostrum raised against Cryptosporidium oocysts and sporozoites has ameliorated infection and disease in some patients with AIDS, and a variety of monoclonal antibodies, as well as hyperimmune bovine colostrum, have significantly reduced cryptosporidial infection of mice and calves. We report here the identification and initial characterization of a > 900,000-M(r) Cryptosporodium sporozoite glycoprotein (GP900) that is a prominent antigen recognized by protective hyperimmune bovine colostral immunoglobulin. Three of six murine anticryptosporidial monoclonal antibodies reacted with GP900, indicating that the molecule is highly immunogenic in mice as well as in cows. GP900 is Triton X-100 soluble and N glycosylated. Western blotting of the N-deglycosylated protein, detected with antibodies eluted from recombinant clones expressing a partial GP900 fusion protein, suggested that the polypeptide backbone of the glycoprotein has an M(r) of < 190,000. GP900 is encoded by a single-copy gene that resides on the largest Cryptosporidium chromosome. PMID- 1452349 TI - Respiratory epithelial cell invasion by group B streptococci. AB - Group B streptococci (GBS) are the most common cause of pneumonia and sepsis during the neonatal period; however, the pathogenesis of this infection is poorly understood. We investigated the ability of GBS to enter epithelial cells in culture. Two strains of GBS were capable of invading immortalized respiratory epithelial cell lines in vitro at different levels, suggesting strain differences in invasiveness. Intracellular replication was not observed. Invasion required actin microfilaments but not microtubular cytoskeletal elements. Active bacterial protein, DNA, and RNA syntheses were required for invasion. These findings are consistent with our previous observation of intracellular GBS in the lungs of infected primates. We hypothesize that this organism may access the bloodstream by direct invasion of the epithelial cell barrier. PMID- 1452350 TI - Early pathogenesis of infection in the liver with the facultative intracellular bacteria Listeria monocytogenes, Francisella tularensis, and Salmonella typhimurium involves lysis of infected hepatocytes by leukocytes. AB - The results show that Listeria monocytogenes, Francisella tularensis, and Salmonella typhimurium are facultative intracellular bacteria with a capacity to invade and grow in nonphagocytic cells in vivo. In the liver, all of these pathogens were seen to invade and to multiply extensively in hepatocytes. In all three cases, inflammatory phagocytes were rapidly marshalled to foci of infection where they appeared to cause the destruction of infected hepatocytes, thereby releasing bacteria into the extracellular space, in which presumably they could be ingested and destroyed by the phagocytes. If phagocytic cells were prevented from accumulating at foci of liver infection by treatment of the mice with a monoclonal antibody (NIMP-R10) directed against the type 3 complement receptor of myelomonocytic cells, then lysis of hepatocytes failed to occur and bacteria proliferated unrestrictedly within them. Under these circumstances, otherwise sublethal infections became rapidly lethal. These findings strongly suggest that lysis of infected hepatocytes by phagocytic cells is an important general early defense strategy against liver infection with at least three different intracellular bacteria. PMID- 1452351 TI - Ovine pulmonary surfactant induces killing of Pasteurella haemolytica, Escherichia coli, and Klebsiella pneumoniae by normal serum. AB - Pulmonary surfactant has been shown to play an increasingly important role in bacterial clearance at the alveolar surface in the lung. This study describes a bactericidal mechanism in which ovine pulmonary surfactant induces killing of Pasteurella haemolytica by normal serum. To demonstrate killing, six bacterial species were incubated first with pulmonary surfactant for 60 min at 37 degrees C and then with serum for an additional 60 min at 37 degrees C. P. haemolytica type A1 strains 82-25 and L101, a P. haemolytica type 2 strain, Escherichia coli, and Klebsiella pneumoniae were susceptible and Pasteurella multocida, Serratia marcescens, and Pseudomonas aeruginosa were not susceptible to killing by ovine pulmonary surfactant and normal serum. No bacteria incubated with bovine pulmonary surfactant were killed by normal serum. Although the species origin of pulmonary surfactant was selective, the species origin of serum was not. P. haemolytica incubated with ovine pulmonary surfactant was killed by fetal calf serum, gnotobiotic calf serum, pooled normal sheep serum, pooled normal rabbit serum, and pooled guinea pig serum. Ultrastructurally, killed P. haemolytica suspensions contained dead cells and cells distorted with vacuoles between the cytoplasmic membrane and the cytoplasm. The mechanism of killing did not correlate with concentrations of complement or lysozyme or titers of residual antibody in either the pulmonary surfactant or the serum, and killing was reduced by preincubation of surfactant with P. haemolytica lipopolysaccharide. Preliminary characterization of both surfactant and serum implicate a low molecular-weight proteinaceous component in the surfactant and serum albumin in the serum. This mechanism may help clear certain gram-negative bacteria from the lungs of sheep as a part of the pulmonary innate defense system. PMID- 1452352 TI - Dual roles for class II major histocompatibility complex molecules in staphylococcal enterotoxin-induced cytokine production and in vivo toxicity. AB - The staphylococcal enterotoxins (SE) specifically bind to class II major histocompatibility complex (MHC) proteins, resulting in activation of monocytes and T cells. The SE cause weight loss in mice, which is dependent on T-cell stimulation and tumor necrosis factor alpha (TNF-alpha) production. Here we use a mutant of staphylococcal enterotoxin A that binds class II MHC molecules and activates monocytes but not T cells to evaluate the relative contributions of monocyte- and T-cell-stimulatory activities to in vivo toxicity. The mutant toxin did not cause weight loss in B10. BR mice but did stimulate monocyte TNF-alpha production in vitro, as did the wild-type toxin. Addition of a supernatant from toxin-activated T cells enhanced monocyte-stimulatory activity of both mutant and wild-type toxins fivefold. The effect of the supernatant could be mimicked by recombinant gamma interferon (IFN-gamma) and was inhibited by antibody to IFN gamma. These results suggest that toxin-induced monocyte TNF-alpha production is upregulated by IFN-gamma, which likely represents the T-cell requirement in SE mediated weight loss. Our studies thus implicate two distinct class II MHC dependent signaling pathways for SE, the first involving direct signal transduction through class II MHC molecules mediated by either mutant or wild type toxin and the second requiring T-cell stimulation by toxin-class II MHC complexes with consequent production of IFN-gamma. We suggest that both pathways are required for optimal monocyte TNF-alpha production in vitro and SE-induced toxicity in vivo. PMID- 1452353 TI - Adherence of Legionella pneumophila to guinea pig peritoneal macrophages, J774 mouse macrophages, and undifferentiated U937 human monocytes: role of Fc and complement receptors. AB - Legionella pneumophila, the causative agent of Legionnaires' disease, is a facultative intracellular pathogen of alveolar macrophages. Although previous studies have demonstrated that specific antibody facilitates uptake of L. pneumophila by phagocytic cells, the role of complement has been unclear. Thus, we have examined the relative contributions of Fc gamma- and complement receptor mediated adherence to guinea pig peritoneal macrophages, U937 human monocytic cells, and J774 mouse macrophage cells. Opsonization of L. pneumophila (Philadelphia 2) with polyclonal immunoglobulin G promoted maximum adherence to guinea pig macrophages. In contrast, incubation in the presence of 20% fresh nonimmune human serum from a single donor did not promote adherence. The results obtained with U937 and J774 cells paralleled those obtained with guinea pig macrophages. In the absence of specific antibody, opsonization with guinea pig complement did not enhance adherence of the Philadelphia 1, Philadelphia 2, or Knoxville strain. However, when complement was added to heat-inactivated, specific antiserum, a fourfold increase in the number of adherent organisms was observed. Blocking studies utilizing membrane receptor-specific monoclonal antibodies demonstrated that both Fc and complement receptors mediated adherence of organisms treated with complement in the presence of specific antibody. These results suggest that complement augments adherence of L. pneumophila only when acting in concert with specific antibody. PMID- 1452354 TI - Streptococcal C5a peptidase is a highly specific endopeptidase. AB - Compositional analysis of streptococcal C5a peptidase (SCPA) cleavage products from a synthetic peptide corresponding to the 20 C-terminal residues of C5a demonstrated that the target cleavage site is His-Lys rather than Lys-Asp, as previously suggested. A C5a peptide analog with Lys replaced by Gln was also subject to cleavage by SCPA. This confirmed that His-Lys rather than Lys-Asp is the scissile bond. Cleavage at histidine is unusual but is the same as that suggested for a peptidase produced by group B streptococci. Native C5 protein was also resistant to SCPA, suggesting that the His-Lys bond is inaccessible prior to proteolytic cleavage by C5 convertase. These experiments showed that the streptococcal C5a peptidase is highly specific for C5a and suggest that its function is not merely to process protein for metabolic consumption but to act primarily to eliminate this chemotactic signal from inflammatory foci. PMID- 1452355 TI - Organization of aerobactin, hemolysin, and antibacterial resistance genes in lactose-negative Escherichia coli strains of serotype O4 isolated from children with diarrhea. AB - Epidemiologically related, non-lactose-fermenting (NLF) Escherichia coli strains of serotype O4 have been isolated at a high frequency from children with diarrhea in Somalia (M. Nicoletti, F. Superti, C. Conti, A. Calconi, and C. Zagaglia, J. Clin. Microbiol. 26:524-529, 1988). In order to define the virulence potential of these strains, we characterized the replication properties of their high molecular-weight plasmids and studied the genetic locations and organization of the aerobactin (aer) and hemolysin (hly) determinants encoded by 23 NLF O4 E. coli strains. Southern blot hybridizations, mobilization assays of nonconjugative plasmids, and incompatibility-exclusion experiments conducted with a conjugative incompatibility group FI (IncFI) plasmid showed that (i) 20 out of the 23 strains examined harbor a 160- to 180-kb IncFI plasmid that shares homology with the basic replicons RepFIA, RepFIB, and (except for the plasmid of one strain) RepFIC, and 22 strains also contain a 40- to 140-kb IncFII plasmid sharing homology with the RepFIIA replicon; (ii) the IncFI plasmid is nonconjugative and carries antibiotic resistance genes; (iii) the aer system is located on the IncFI plasmids and/or the chromosomes in the three strains not harboring IncFI, and it is found in an inverted orientation; (iv) the hly determinants are located on the chromosome, and their genetic organization is well conserved and closely resembles that of the reference hemolytic plasmid pHly152; and (v) Hly- mutants obtained by transposon insertion mutagenesis are not cytotoxic to HeLa cell monolayers, indicating that hemolysin is responsible for the high cytotoxic activity we have previously reported for these strains. The structural organization of the plasmid-encoded aer operon, together with the finding that those plasmids also carry antibiotic resistance genes, indicates that the IncFI plasmid of the NLF O4 E. coli strains studied more closely resembles aer-encoding virulence IncFI Salmonella R plasmids than E. coli ColV plasmids. The data presented here cannot rule out whether the strains examined are potentially intestinal or extraintestinal pathogens. Nevertheless, the genetic organization of the virulence genes, together with the epidemiological behavior and the wide spectrum of antibiotic resistance of the NLF O4 E. coli strains, indicates that these strains are structured as typical E. coli pathogenic isolates of human origin. PMID- 1452356 TI - Histological and immunocytochemical characterization of Coxiella burnetii associated lesions in the murine uterus and placenta. AB - The fetoplacental units and the postgravid uterus of BALB/cJ (H-2d) mice inoculated intraperitoneally with Coxiella burnetii (Nine Mile isolate, phase I) on day 6 of pregnancy were examined histologically and immunocytochemically at 1 to 160 days postinoculation. Clinically, abortions, stillbirths, and perinatal deaths were observed. Histological lesions in the placenta were characterized by severe necrosis of the decidua basalis and the labyrinth, fibrinoid degeneration of decidual vessels, and microthrombosis. Pyometra and endometritis at the sites of previous placental attachment, characterized by ulceration, central necrosis, and moderate cellular infiltration consisting of neutrophils and macrophages, were observed postpartum. Pups sacrificed at the age of 9 days exhibited interstitial pneumonia with few granulomas and granulomatous hepatitis and splenitis. Immunocytochemically, antigen-bearing cells were first detected in the decidua 9 days postconception, and single immunopositive cells were detected in the fetal placenta 4 days later. Thereafter, until abortion or parturition, abundant accumulation of C. burnetii antigen was observed in the maternal and fetal compartments of the placenta. Up to 28 days postinoculation, many immunopositive cells were demonstrated at the sites of previous placental attachment, whereas the adjacent endometrium contained only a few antigen positive cells. C. burnetii antigen was demonstrated in decidual cells, trophoblasts, and macrophages and extracellularly within the sinuses of the labyrinth and in the uterine lumen but not in granulated metrial gland cells. Fetuses in utero and aborted, stillborn, or perinatally dying offspring were immunocytochemically negative for C. burnetii antigen; however, pups killed 9 days after birth showed lesion-associated positive immunoreaction in the lung, liver, and spleen. The present study shows that infection with C. burnetii during pregnancy results in uncontrolled growth of the organism in the murine uteroplacental unit and that associated lesions are characterized by necrosis of placental tissues, fibrinoid degeneration of decidual vessels, and microthrombosis. PMID- 1452357 TI - Yersinia pestis YopM: thrombin binding and overexpression. AB - In previous studies, Yersinia pestis YopM has been shown through mutational analysis to be necessary for virulence in mice and found to have homology with the thrombin-binding domain of the platelet receptor GPIb alpha. In this study, YopM was purified and shown by dot blot and chemical cross-linking tests to bind to human alpha-thrombin. No cross-linked product could be detected when human prothrombin was incubated with YopM. As a functional test of thrombin binding, it was shown that native but not boiled YopM inhibits thrombin-induced aggregation of human platelets. Control tests showed that YopM did not inactivate the platelets themselves, nor was its effect a nonspecific consequence of its very acidic isoelectric point. Microsequencing of YopM revealed an intact N terminus, indicating that functional YopM is not processed at the N terminus or secreted by a mechanism involving a cleavable signal sequence. Further characterization was made of an interesting effect on yopM expression that had been noticed in a previous study. A 1.5-kb HaeIII subclone overexpressed YopM in both Y. pestis and Escherichia coli compared with a larger clone containing the 5.3-kb HindIII-F fragment. To search for a possible regulator of YopM expression, the HindIII-F fragment was sequenced, revealing several open reading frames and three large repeated sequences. Deletional analysis showed that these were not involved in regulation of yopM. The data implicated a DNA structure 5' to yopM in moderating yopM expression. PMID- 1452358 TI - Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha. AB - Inflammatory mediators produced by cells in the gingiva have been implicated in the initiation and progression of periodontal disease, a common infectious disease. In this study, we examined the biological activity of neutrophil chemotactic factors and the kinetics of expression of interleukin-8 (IL-8) mRNA derived from normal gingival fibroblasts in response to inflammatory mediators in an in vitro model. Gingival fibroblasts stimulated by either recombinant human interleukin-1 beta or recombinant human tumor necrosis factor alpha produced neutrophil chemotactic factors after 4 h, whereas expression of cell-derived IL-8 mRNA was detected within 1 h after stimulation. Furthermore, in a neutralization assay, rabbit anti-recombinant human IL-8 antiserum inhibited neutrophil chemotactic activity to basal levels. These results provide evidence that gingival fibroblasts synthesize potent chemotactic factors such as IL-8 in the presence of the inflammatory mediators interleukin-1 beta and tumor necrosis factor alpha. The activity of these factors may contribute to neutrophil-mediated processes in the pathogenesis of periodontal disease. PMID- 1452359 TI - Purification and characterization of the urease enzymes of Helicobacter species from humans and animals. AB - The urease enzymes of Helicobacter pylori, H. mustelae, H. felis, and H. nemestrinae have been purified to homogeneity by affinity chromatography and characterized. The native urease enzymes of the four organisms were found to be almost identical, with a pI of 6.1 and molecular masses of 480 to 500 kDa, as determined by electrophoretic mobility in nondenaturing polyacrylamide gels. Transmission electron microscopy of the native urease showed it to be a molecule approximately 13 nm in diameter, with hexagonal symmetry. Denaturation studies indicated that each urease enzyme molecule was composed of two nonidentical subunits with molecular masses of approximately 64 and 30 kDa. The subunits were present in a 1:1 ratio, suggesting a hexameric stoichiometry for the native molecule. The predicted molecular mass of H. pylori urease, based on subunit molecular weight and stoichiometry, is 568 kDa. N-terminal amino acid sequencing of the enzyme subunits from the four species revealed high levels of homology. The large subunits (UreB) were found to be 92 to 100% homologous, and the small subunits (UreA) were 75 to 95% homologous over the first 12 to 20 residues. The high degree of homology suggests a common ancestral origin and an important role for the urease enzymes of these organisms. PMID- 1452360 TI - Clonal and antigenic analysis of serogroup A Neisseria meningitidis with particular reference to epidemiological features of epidemic meningitis in the People's Republic of China. AB - Representative strains of serogroup A Neisseria meningitidis were chosen from all major meningitis epidemics worldwide since 1960 and subjected to analysis for the electrophoretic variation of 15 cytoplasmic allozymes and four outer membrane proteins. The 290 strains defined 84 unique electrophoretic types which were classified in nine subgroups. Tests with monoclonal antibodies specific for conserved pilin epitopes showed that the class I, IIa, and IIb epitopes were uniform within the subgroups. Similarly, the subgroups were uniform for expression of different variable regions of class 1 outer membrane protein, with a few minor exceptions. Many of the bacteria tested were isolated in the People's Republic of China, and the epidemiology of Chinese epidemics of meningococcal meningitis is described. The analysis approaches a global description of epidemic meningitis caused by serogroup A meningococci in the past 30 years. PMID- 1452361 TI - Intestinal changes associated with expression of immunity to challenge with Eimeria vermiformis. AB - To provide more information on the mechanisms involved in the immune inhibition of eimeria infections, NIH mice were adoptively immunized against infection with Eimeria vermiformis by the transfer of mesenteric lymph node cells from primed animals and homologously challenged. Subsequent changes in the architecture and cellular composition of the intestine were compared with those observed in similarly challenged susceptible control mice and correlated with the development of the parasite in the two groups. Actively immunized mice were also examined. In adoptively immunized mice, the development of E. vermiformis was inhibited within 3 days of administering the challenge inoculum. Concurrent changes in the intestine included lymphocytic infiltration, crypt hyperplasia, flattening of the crypt epithelium, and a reduction in the number of Paneth cells. Hyperplasia of goblet and pyroninophilic cells in response to challenge, although accelerated and enhanced in adoptively immunized hosts, occurred after the inhibition of the parasites, and mastocytosis was not observed in these animals, findings which suggest that the activities of goblet, pyroninophilic, and mast cells were not instrumental in reducing the numbers of parasites. The intestines of immunized mice contained fewer intraepithelial lymphocytes at the time of inhibition of the parasites than did those of the controls. The protective effects and intestinal changes described above did not differ appreciably from those seen after challenge of mice that had been immunized by infection. PMID- 1452362 TI - An 87-kilodalton glucan-binding protein of Streptococcus sobrinus B13. AB - An 87-kDa glucan-binding protein (GBP) of Streptococcus sobrinus B13 (serotype d) was isolated and purified from extracellular culture supernatant by using affinity chromatography on Sephadex G-50 and elution with a guanidine HCl gradient. Western blot (immunoblot) analysis showed it to be antigenically related, but not completely identical, to the 74-kDa GBP of Streptococcus mutans Ingbritt. The 87-kDa GBP has no glucosyltransferase activity. A possible role for this GBP in the cariogenicity of S. sobrinus B13 is suggested. PMID- 1452363 TI - Frequency of antigen-specific B cells during experimental ocular Chlamydia trachomatis infection. AB - Chlamydia-specific antibody-secreting cells have been identified in conjunctiva and draining cervical lymph nodes by an ELISPOT assay in a cynomolgus monkey model of trachoma. These local sites contained numbers of chlamydia-specific B cells that were higher than those in distant inguinal lymph nodes and peripheral blood. The numbers of chlamydia-specific immunoglobulin G-secreting B cells observed were 5 to 57 per 10(6) cells in conjunctiva and 24 to 996 per 10(6) cells in cervical lymph nodes during conjunctival infection or after challenge of immune monkeys with the chlamydial 57-kDa heat shock protein (hsp60). These studies demonstrate a large chlamydia-specific B-cell component in the conjunctiva during ocular chlamydial infection. These results are similar to our findings for chlamydia-specific T-cell responses. PMID- 1452364 TI - Studies with enteroaggregative Escherichia coli in the gnotobiotic piglet gastroenteritis model. AB - Two strains of enteroaggregative Escherichia coli of human origin fed to gnotobiotic piglets caused diarrhea or death in the majority of them. Histological examination revealed moderate hyperemia of the distal small intestine and cecum, swelling of small intestinal villi, and layers of aggregated bacteria stacked together in a mucus gel-like matrix overlying intact epithelium. These findings confirm that enteroaggregative E. coli strains produce distinctive intestinal lesions different from those caused by other major categories of diarrheagenic E. coli. PMID- 1452365 TI - Alteration of cytoplasmic Ca2+ in resting and stimulated human neutrophils by short-chain carboxylic acids at neutral pH. AB - The results reported here indicate that the short-chain carboxylic acids acetate and propionate stimulate cytoplasmic calcium mobilization in human polymorphonuclear leukocytes, while butyrate and lactate do not. Together with the results of previous work, this indicates that there are at least three classes of short-chain carboxylic acids: those which can alter only cytoplasmic pH (e.g., lactic acid), those which can alter cytoplasmic pH and actin (e.g., butyric acid), and those which can alter cytoplasmic pH, actin, and calcium (e.g., acetate and propionate). PMID- 1452366 TI - Encystation of Giardia lamblia leads to expression of antigens recognized by antibodies against conserved heat shock proteins. AB - During in vitro encystation, Giardia lamblia expresses several stage-specific proteins which are recognized in immunoblots by antisera raised against antigens from three different pathogens. The antigens belong to two different families of conserved stress proteins: (i) HSP60 purified from Legionella pneumophila and recombinant HSP60 from Mycobacterium bovis BCG and (ii) recombinant HSP70 from Plasmodium falciparum. PMID- 1452367 TI - A bactericidal monoclonal antibody specific for the lipooligosaccharide of Bordetella pertussis reduces colonization of the respiratory tract of mice after aerosol infection with B. pertussis. AB - A mouse immunoglobulin G3 monoclonal antibody specific for the core oligosaccharide moiety of the lipooligosaccharide (LOS) of Bordetella pertussis has been shown to have complement-dependent bactericidal activity. This monoclonal antibody exhibits bactericidal activity against strains of B. pertussis that express the LOS A phenotype. In addition this monoclonal antibody was effective in reducing colonization by B. pertussis in both the lungs and tracheas of mice after aerosol infection. PMID- 1452368 TI - Effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in rats. AB - The aim of this study was to determine the effects of duration of pressure overload on the reversibility of impaired coronary autoregulation in hypertropied hearts. The experiments were performed on 38 anesthetized male Wistar rats aged 6 to 8 weeks. The ascending aorta was banded for 4 or 10 weeks, then in some rats the bands were removed for 4 weeks. We estimated coronary hemodynamics in a model consisting of isolated non-working hearts perfused with Tyrode's solution containing bovine red blood cells and serum albumin. Myocardial mass increased significantly in 4 and 10-week banded groups compared to controls. Four weeks after debanding in 4- and 10-week banded groups, the value returned to that of controls. Autoregulation gain was significantly lower in banded groups than in controls in the range between 50 and 100 mmHg of coronary perfusion pressure. Although the gain normalized in the debanded group after 4 weeks of banding, the value in the debanded groups after 10 weeks of banding remained less than zero between 25 and 150 mmHg of perfusion pressure. In transient flow response to a stepwise increase of perfusion pressure within the autoregulatory range, promptly increased flow was followed by more rapid and greater decrease in controls than in banded groups. The flow response regressed in the debanded group after 4 weeks of banding, while it remained unchanged in the debanded group after 10 weeks of banding. Thus, duration of pressure overload alters the regression of impaired coronary autoregulation in cardiac hypertrophy. PMID- 1452369 TI - Serum cortisol levels predict infarct size and patient mortality. AB - We have investigated prospectively the serum cortisol response to acute myocardial infarction in 70 consecutive patients admitted to a coronary care unit and we have shown that the levels are significantly raised early in the course of the illness and prior to elevation of the cardiac specific enzyme fraction, creatine kinase MB. The magnitude of the cortisol response is related to the size of the ensuing infarction (rs = 0.54) as calculated from the total creatine kinase MB release (P < 0.001) and very high levels (> 2000 mumol/l) are predictive of mortality (P < 0.05). Serum cortisol levels may have a role in the early identification of myocardial infarction and in predicting those patients with a poor prognosis. PMID- 1452370 TI - Non-invasive evaluation of cardiac abnormalities in heat stroke pilgrims. AB - Serial electrocardiograms as well as echocardiographic studies of 51 pilgrims suffering from acute heat stroke (mean rectal temperature 41.6 degrees C) were performed. All patients were examined immediately after cooling and 24 h later whenever possible. Regional wall motion abnormalities were detected in 9 cases (17.6%) while pericardial effusion was observed in 13 cases (25%) and asymmetrical septal hypertrophy was detected in 8 cases (15.6%). Other cardiac abnormalities included right ventricular dilatation and increased in left ventricular internal dimensions in 4 cases (7.8%), respectively. Thirteen cases (25.5%) had normal echocardiographic findings. Forty (78%) patients had sinus tachycardia while 8 cases (15.7%) showed atrial fibrillation with uncontrolled ventricular rate, and 3 (5.8%) had sinus bradycardia. Heat stroke electrocardiograms showed tracings demonstrating ST segment depression, compatible with ischaemia in 9 cases, while in 6 cases there were nonspecific T wave changes, whereas in another 4 cases the tracings demonstrated different conduction abnormalities. The collected data were analysed and compared to those of 43 control patients. The adverse effects of heat stroke on the heart are multifactorial requiring the utmost attention and understanding, as they reflect the patient's cardiovascular status. PMID- 1452372 TI - Acute myocardial ischemia resulting in dynamic obstruction to the left ventricular outflow relieved by successful angioplasty. AB - A patient was admitted because of an acute myocardial infarction which evolved with heart failure and postinfarction angina. A pattern consistent with dynamic left ventricular outflow obstruction was found. It disappeared after coronary angioplasty was performed on the vessel responsible for the ischemia. PMID- 1452371 TI - Right ventricular volumes and hemodynamics after successful orthotopic heart transplantation. A comparison to coronary artery disease using thermodilution. AB - Only few data exist concerning right ventricular function in the chronic stage after cardiac transplantation. Therefore, we investigated hemodynamic and right ventricular volumetric data by a computerized thermodilution Swan-Ganz catheter in 17 patients (median age: 53, range: 18-63 yr) at a median of 24 (4 to 44) months after cardiac transplantation during rest and supine bicycle exercise. Myocardial biopsy showed grade one or less according to the classifications of Billingham. Sixteen patients with coronary artery disease, but without prior myocardial infarction, served for comparison. While angiographic left ventricular ejection fraction was nearly identical in transplant recipients [77 (60-92)%, median (range)] and in patients with coronary artery disease [78 (64-94)%], right ventricular ejection fraction was lower (p < 0.001) in patients after cardiac transplantation [37 (16-58)%] as compared to patients with coronary artery disease [56 (46-62)%]. In transplant recipients right atrial pressure was significantly higher both at rest [10 (2-18) mmHg] and exercise [18 (8-30) mmHg] than in patients with coronary artery disease [5 (1-11) and 8 (3-18) mmHg]. Pulmonary capillary wedge pressure behaved similar in both groups. To further evaluate reasons for right ventricular impairment, a correlation analysis was performed. This showed a negative correlation between right ventricular ejection fraction and the time interval after transplantation (p < 0.0002). However, there was no correlation between right ventricular ejection fraction and acute rejection or a rejection score. In conclusion, right ventricular function may be severely altered in transplant recipients, in contrast to an only slight impairment of left ventricular function. PMID- 1452373 TI - The impact of thrombolytic therapy on hospital mortality from acute myocardial infarction in the Chinese in Hong Kong. AB - Thrombolytic therapy using recombinant-tissue plasminogen activator, urokinase and streptokinase for acute myocardial infarction was instituted in the coronary care unit of the Prince of Wales Hospital in Hong Kong in 1988. To evaluate its impact on hospital mortality of acute myocardial infarction, the database of 465 patients (mean age 65.2 +/- 12.6 yr) admitted into the coronary care unit in the period between 1985-1990 was collected prospectively and their clinical course reviewed. Three hundred and thirty-five patients were males and 130 were females. Patients in the prethrombolytic era (1985-87) and the thrombolytic era (1988-90) were matched for age, proportion of females and clinical severity. One hundred and two patients (39.5%) received thrombolytic therapy. The overall hospital mortality (18.6%) in the thrombolytic era and that for each sex (18.2% in the males; 19.5% in the females) were significantly lower than those of prethrombolytic era (27.1%, 23.4% and 37.7%, respectively). No death was due to bleeding complication. The benefit of thrombolytic therapies in the Chinese was confirmed. More effort is needed to popularize this concept in the Chinese communities, to shorten the prehospital delay of patients and to extend its utilisation to the elderly patients. PMID- 1452374 TI - Effect of diltiazem on silent ischemic episodes, plasma bradykinin and prostaglandin metabolism. AB - Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase > or = 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses. PMID- 1452375 TI - Prodromal chest pains: clues to the pathogenesis of non-Q wave acute myocardial infarction? AB - Prodromal chest pains were recorded from consecutive admissions to a single coronary care unit and the symptoms of those with Q wave and non-Q wave acute myocardial infarction were compared. Of 809 admissions there were 201 with Q wave ad 88 with non-Q wave infarction. The non-Q wave infarction group was older, included more women and a greater proportion had suffered a previous myocardial infarct. Effort angina was equally common in both groups, but in the Q wave infarction group, angina was more often of recent onset, within the previous 4 weeks. Symptoms to indicate worsening angina, more prolonged, intense or frequent pain, were equally common in both groups. These findings suggest that although the extent of coronary artery disease may differ, Q wave and non-Q wave myocardial infarction share a common pathogenic mechanism. PMID- 1452376 TI - Thrombolysis following pre-hospital cardiopulmonary resuscitation. AB - Forty-eight patients were discharged from hospital following successful resuscitation from out-of-hospital ventricular fibrillation. Sixteen of these patients received intravenous thrombolytic therapy on admission to hospital. There were 3 significant bleeding complications and 2 cases of inappropriate administration of streptokinase. One of the patients that did not receive thrombolysis also had a significant bleeding complication of cardiopulmonary resuscitation. Patients admitted to hospital following resuscitation should only receive thrombolytic therapy when there is overwhelming electrocardiographic evidence of acute myocardial infarction, and even then with caution. PMID- 1452377 TI - Radiofrequency catheter ablation for treatment of Wolff-Parkinson-White syndrome- short- and long-term follow-up. AB - One hundred and twenty-five patients with accessory pathways mediated tachyarrhythmias underwent radiofrequency ablation. Right-sided accessory pathways were ablated from the atrial aspect of the tricuspid anulus (all from the femoral vein approach) and the left-sided accessory pathways were ablated from the atrial or ventricular aspect of the mitral anulus. Immediately after the procedures, 3 of 8 accessory pathways (38%) and 131 of 137 accessory pathways (95%) were ablated successfully with radiofrequency through a small-tip (2 mm) and a large-tip (4 mm) electrode catheter, respectively. Seven of the 11 accessory pathways that failed radiofrequency ablation had a later successful direct current ablation. During follow-up (3 to 22 months), serial electrophysiological study showed that 11 of the 114 patients (10%) with successful ablation had return of accessory pathway conduction (2 had recurrence of tachycardia, 2%). Complications included accidental AV block (1 patient), cardiac tamponade (1 patient) and possible aortic dissection (1 patient). Transient proarrhythmic effects (more atrial and ventricular premature beats) were seen during the first week and sustained ventricular tachyarrhythmias were not inducible. In a successful session, procedure and radiation exposure times (including the time for diagnostic procedures) were 3.8 +/- 0.2 h and 45 +/- 4 min, respectively. This study confirms that radiofrequency ablation with a large tip electrode catheter is an effective and relatively safe nonsurgical method for treatment of Wolff-Parkinson-White syndrome, with a low complication and recurrence rate. PMID- 1452378 TI - Acute and chronic performance of a steroid eluting electrode for ventricular pacing. AB - Studies have demonstrated consistently low stimulation thresholds in the first months following implantation of steroid eluting electrodes. There have been no reported cases of exit block. There is little information on the long-term performance of these leads. Data were collected on 15 patients in whom Medtronic steroid eluting leads (5023 and 4003) had been implanted in 1987. Stimulation thresholds were measured at implantation and at weeks 1, 2, 3, 4, 5, 6 and 12. Stimulation threshold, lead impedance and sensing thresholds were monitored periodically for 3 yr using the telemetered function of the pulse generator. Three-month follow-up was obtained in all the patients and 3-yr follow-up in 10. Stimulation thresholds remained low throughout the follow-up period in all but one patient who developed exit block necessitating the replacement of the pacing system. In the remaining patients there was a significant increase in mean stimulation threshold from implantation to week 1 (mean stimulation threshold at implantation = 0.106 ms, mean ST at week 1 = 0.182 ms; p = 0.05), and also a gradual increase in the stimulation threshold over the first 2 yr of follow up (mean stimulation threshold 1 week = 0.182 ms, mean stimulation threshold months 13-24 = 0.243 ms; p = 0.05). Lead impedance showed no significant change over the follow-up period (mean change in impedance = 4.3 omega, SD 163.2, p = 0.97). Unlike many conventional electrodes, steroid eluting leads show no early peak in stimulation threshold but exit block can occur. Stimulation thresholds show a small but significant rise over time. PMID- 1452379 TI - Biophysical parameters of radiofrequency catheter ablation. AB - Radiofrequency catheter ablation has been shown to be an effective treatment for patients with accessory pathways in Wolff-Parkinson-White syndrome and other supraventricular tachycardias. However, the biophysical parameters used so far in vivo did not correlate to the size of myocardial lesions and provided no information about the myocardial wall contact of the electrode. In this study 104 radiofrequency applications were performed on excised pig myocardium in circulating heparinized pig blood as well as in blood alone, and root mean square (rms) voltage, root mean square current and phase angle were measured using a specially developed device. The calculated effective power and output power differed by only 2-7% when measured at the point of maximum current during coagulation. A drop of current following a rise in impedance led to a phase displacement of more than 80 degrees and thereby to a drop of effective power to 17% of the output power. Hence, apparent output power consists mainly of ineffective power. The time dependent variations of phase angle, impedance and current were found to be useful for distinguishing between the media blood and myocardium. These results show that physical parameters measured during radiofrequency catheter ablation may help to control electrode position in the clinical situation and reduce the number and duration of ineffective energy applications. PMID- 1452380 TI - Left ventricular function response to exercise in normotensive obese subjects: influence of degree and duration of obesity. AB - This study has been designed to evaluate whether duration and severity of obesity can influence left ventricular function response to exercise in obese subjects without other known cardiovascular risk factors such as hypertension, diabetes or hyperlipoproteinemia. A total of 29 obese subjects were included and they were divided, according to their body mass index and to Garrow's criteria as follows: Overweight or mildly obese subjects: body mass index from 25 to 30 kg/m2; moderately obese subjects: body mass index > 30 and < 40 kg/m2. Both obese groups were further subdivided according to their duration of obesity evaluated by accurate anamnesis in subgroup A (duration of obesity less than 120 months) and subgroup B (duration of obesity more than 120 months). Left ventricular ejection fraction was detected by blood pool gated radionuclide angiocardiography both at rest and after symptom-limited bicycle ergometer procedure. At peak exercise left ventricular ejection fraction increased significantly (p < 0.05) only in overweight subjects. Exercise produced an increase of left ventricular ejection fraction in 14 overweight and in 5 moderately obese subjects and a decrease in 2 moderately obese subjects. At peak exercise mean heart rate and mean blood pressure increased significantly (p < 0.001) in both groups. When obese subjects were subgrouped according to duration of obesity, left ventricular ejection fraction increased significantly (p < 0.05) only in overweight subjects with duration of obesity less than 120 months. Duration of obesity correlated inversely with percent change in left ventricular ejection fraction (EF) at peak exercise (delta EF) (r = -0.59; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452381 TI - Antihypertensive effects of low doses of hydrochlorothiazide in hypertensive black Zimbabweans. AB - The antihypertensive effects of low doses of hydrochlorothiazide have not been examined in black African hypertensive patients although hydrochlorothiazide is commonly used as first-line therapy. The antihypertensive effects of hydrochlorothiazide in a daily dose of 6.25, 12.5, 25 and 50 mg were examined in 19 black Zimbabwean hypertensive patients in a double-blind, random order, placebo-controlled, cross-over trial. The mean systolic blood pressure on placebo was 170.2 mmHg (95% CI +/- 9.0 mmHg) and on daily doses of hydrochlorothiazide decreased to: 161.1 mmHg (95% CI + 10.0 mmHg) on 6.25 mg; 156.6 mmHg (95% CI +/- 8.6 mmHg) on 12.5 mg; 154.9 mmHg (95% CI +/- 8.5 mmHg) on 25 mg and 149.1 mmHg (95% CI +/- 9.2 mmHg) on 50 mg. The mean diastolic blood pressure on placebo was 101.4 mmHg (95% CI +/- 5.0 mmHg) and decreased to: 98.0 mmHg (95% CI +/- 5.7 mmHg) on 6.25 mg; 96.1 mmHg (95% CI +/- 4.5 mmHg) on 12.5 mg; 93.6 mmHg (95% CI +/- 5.3 mmHg) on 25 mg and 90.5 mmHg (95% CI +/- 3.9 mmHg) on 50 mg. Hydrochlorothiazide in doses of 25 mg and 50 mg decreased systolic and diastolic blood pressure and the 12.5 mg dose decreased systolic blood pressure significantly more than placebo. We conclude that in this population maximum antihypertensive effect is not seen with the lower doses of hydrochlorothiazide and 25 mg is an appropriate starting dose for most patients. PMID- 1452382 TI - Echocardiographic variables affecting surgical outcome in patients undergoing closed mitral commissurotomy. AB - We studied, by transthoracic cross-sectional echocardiography, the influence of subvalvar pathology on the early hemodynamic result of closed mitral commissurotomy in 132 patients with severe rheumatic mitral stenosis (56 males, 76 females, mean age 25.2 yr, range 10-55) in our tertiary care hospital in North India from July 89 to December 91. The mitral subdistance ratio was calculated by dividing the distance between the papillary muscle tip and mitral valve in systole (apical 4-chamber view) by left ventricular diastolic length (apical long axis view). Nineteen patients with mild subvalvar pathology (mitral subdistance ratio > 0.18) and 71 patients with moderate, achieved a larger valve area (2.26 cm2 SD 0.54) than 42 patients with severe subvalvar pathology (mitral subdistance ratio < 0.12, postoperative valve area 2.09 cm2 SD 0.6, p < 0.05). In addition, 9 of these 42 patients (21%) developed significant mitral regurgitation (4 deaths), in contrast to 1/19 with mild and 6/71 with moderate subvalvar pathology. We conclude that echocardiography identifies patients with severe subvalvar pathology who fare poorly after closed mitral commissurotomy. However, this procedure would still be practised in developing countries like ours due to financial constraints. PMID- 1452383 TI - Simultaneous measurement of left atrial pressure by Doppler echocardiography and catheterization. AB - Simultaneous, continuous wave Doppler echocardiography, left ventricular systolic and mean pulmonary capillary wedge pressure measurements were performed during cardiac catheterization in 54 patients with mitral regurgitation. Doppler-derived left atrial pressure, which was calculated by subtracting mitral regurgitant gradient from brachial artery systolic pressure, correlated well with mean pulmonary capillary wedge pressure by catheter (r = 0.933, SEE = 2.9 mmHg, P < 0.001); a comparison between non-invasive and invasive systolic gradients across the mitral valve yielded a high correlation (r = 0.91, SEE = 6.0 mmHg, P < 0.001); and there was also a high correlation between brachial artery and left ventricular systolic pressures (r = 0.93, SEE = 4.9 mmHg, P < 0.01). It is concluded that Doppler echocardiography provides a reliable and accurate method for complete non-invasive assessment of left atrial pressure in patients with mitral regurgitation. PMID- 1452384 TI - Left-atrium-to-right-ventricle shunting after surgery for atrioventricular septal defect: an unusual sequel detected by transesophageal echocardiography. AB - A 25-yr-old female who had undergone surgery for common atrium and atrioventricular septal defect at the age of 9, was found to have residual shunting at the level of the atrioventricular junction. Precordial echocardiography failed to assess the direction of the shunt. Transesophageal echocardiography showed dehiscence of the atrial patch at the level of the atrioventricular junction. Through this defect left-atrium-to right ventricle shunting occurred in diastole, whereas in systole the defect was closed by the juxtaposition of the anterior tricuspid valve leaflet. PMID- 1452385 TI - Right atrial thrombus in constrictive pericarditis. AB - We describe right atrial thrombus complicated by tricuspid valve obstruction in a patient with constrictive pericarditis. This report highlights the role of surgical thrombectomy, and the investigation of constrictive pericarditis to exclude intra-cardiac thrombus. PMID- 1452386 TI - Pericardial metastasis and effusion as the initial manifestation of malignant thymoma: identification by cross-sectional echocardiography. PMID- 1452387 TI - Hypoplastic right ventricle with mild pulmonary stenosis in an adult. AB - A rare cyanotic heart disease surviving to adulthood with minimal symptoms is presented. The final diagnosis was hypoplastic right ventricle with mild pulmonary stenosis, where the latter was not responsible for the right-to-left shunting across a large atrial septal defect. The differences from cases reported in the literature are highlighted. PMID- 1452388 TI - Multichamber intracardiac thrombi in a patient without any predisposing cardiac or non-cardiac disease. AB - A patient who developed multichamber (left ventricle, right ventricle, right atrium) intracardiac thrombi without having any predisposing cardiac or non cardiac disease is discussed. The thrombi were diagnosed echocardiographically and confirmed histopathologically. The occurrence of multichamber mural thrombi without any predisposing disease is extremely rare. Risk factors for their development have been reviewed. PMID- 1452389 TI - Coping and maintenance strategies of spontaneous remitters from problem use of alcohol and heroin in Switzerland. AB - A short review of the literature is followed by data from a Swiss study on spontaneous remission from problem use of alcohol and heroin conducted in 1988. The analysis of the collected life histories led to the identification of a motivation phase, a stage of decision implementation, and a struggle for maintenance as the major sequence of the autoremission process. The discussion focuses on the "tools" which remitters use to put their decision into practice. The coping mechanisms identified are "diversion," "self-monitoring," and "distancing." In relation to the maintenance phase, the perception of possible relapse situations and intuitive predictions of the subjects and collaterals are analyzed. PMID- 1452390 TI - Alcohol-related problems encountered by Japanese, Caucasians, and Japanese Americans. AB - Using population-based survey data, personal-problematic and socioproblematic factors were examined among Japanese in Japan, Japanese-Americans in Hawaii, and Japanese-Americans; Caucasians in California were analyzed as a control group. Caucasian males were more likely to exhibit drinking-related social problems, whereas Japanese males showed more personal-problematic symptoms. Japanese American men, both in Hawaii and California, were least likely among the three ethnic groups to have personal-problematic symptoms and were more likely to have socioproblematic symptoms than Japanese men. These differences might be explained by differences in the perception of social problems. PMID- 1452391 TI - Voluntary agencies dealing with drug and alcohol misusers: a comparison of three surveys conducted in London, Scotland, and Tasmania. AB - A comparison is presented of three independent surveys of voluntary agencies dealing with drug misusers in London, Scotland, and Tasmania. The comparison shows that in all three locations: (1) agencies demonstrate a recent and rapid growth, are predominantly small and rely on the commitment of a few workers, are heavily dependent on government funding and most funds are spent on salaries; (2) staff are largely unqualified and recently appointed, see their primary activity as counseling; and (3) clients are predominantly male. The community base of these agencies means wide variability in type of agency and creates problems in assessing success and in developing relationships between them and agencies in the statutory sector. PMID- 1452392 TI - Behavioral characteristics of seroconverted intravenous drug users. AB - A total of 440 participants (218 in 1987 and 222 in 1988) were recruited from methadone maintenance clinics in New York City. After obtaining informed consent, a standardized questionnaire was administered. Also, sera were collected and tested for HIV antibody. The overall HIV infection rate was 60% in 1987 and 52% in 1988. In 1987 and 1988, respectively, 19 of 23 and 23 of 40 participants who admitted to a previous HIV seronegative result were found to test HIV seropositive. The behavioral factors which differentiated suspected seroconverters from participants who remained seronegative were frequencies of sharing needles (p < .01), sharing cookers (p < .02), and use of shooting galleries (p < .05) during the last 5 years. Needle-sharing behaviors continue to be associated with HIV seroconversion among IVDUs. More effective education to stop needle sharing among IVDUs is needed. PMID- 1452393 TI - Outpatient care participation and six-month status: results with an inner city impoverished alcoholic veterans population. AB - One hundred and thirty-seven impoverished, inner city, predominately Black alcoholic veterans were divided into four groups based on the frequency of their attendance at an outpatient clinic. They were assessed 6 months after their joining the clinic. In general, many variables reflecting lessened alcohol consumption were connected with greater amounts of clinic attendance. In most instances a month or more of attendance at the clinic appeared necessary before the positive changes started to occur. PMID- 1452394 TI - Mortality associated with drug misuse among blacks in New York City, 1979-1981. AB - A comparison of age-specific death rates from "drug dependence" (ICD 304) among Blacks and Whites in New York City for 1979-1981 found two distinct patterns of mortality. Blacks have higher levels of mortality which extend from the central adult years into middle age while deaths among Whites are confined largely to the younger years (below 35). Among both racial groups, mortality is much higher for males than for females. When male undercount is "corrected," the ratios between male and female deaths are smaller. The difference in economic opportunities for Whites and Blacks is suggested as a reason why Whites "age out" of the years of highest risk before Blacks. PMID- 1452395 TI - Violence and illegal drug use among adolescents: evidence from the U.S. National Adolescent Student Health Survey. AB - The relationships between violence, drug use, and victimization were examined in a representative sample of American adolescents. The commonly used illegal drugs (marijuana, amyl/butyl nitrites, psychedelics, amphetamines, and cocaine) and alcohol were considered. Drug users, compared to nonusers, fought more, took more risks which predisposed them to assault, and were assaulted more both at school and outside school supervision. Adolescents who were victims at school were also more likely to be victimized outside of school supervision. This study clearly demonstrates that the aggressor may also be the victim, and that illegal drug/alcohol use is related to victimization. PMID- 1452396 TI - Does the codependent encourage substance-dependent behavior? Paradoxical injunctions in the codependent relationship. AB - It is argued that the paradoxical nature of the power structure within the codependent relationship places limits on the types of control strategies that codependents can utilize in their attempts to extinguish their partner's substance-dependent behavior. From a social exchange and learning theory perspective, it is argued that the types of control strategies that codependents utilize are not only ineffective, but they actually operate to strengthen the likelihood that substance misuse will be repeated in the future. Types of communication behaviors that codependents utilize in order to control are considered, along with ensuing implications for intervention. PMID- 1452397 TI - Alcohol and other drug use among adolescents with disabilities. AB - This study assessed the incidence rates of alcohol and other drug (AOD) use among a sample of five groups of adolescents: (1) nondisabled students, (2) learning disabled students, (3) behaviorally disordered/less aggressive students, (4) behaviorally disordered students, and (5) behaviorally disordered/self-contained students. The learning disabled, behaviorally disordered/less aggressive, and nondisabled students reported similar AOD use rates. The behaviorally disordered/self-contained students reported substantially more AOD use than the other groups. The behaviorally disordered students reported higher usage of some AODs, but the differences were not as dramatic as those of the behaviorally disordered/self-contained group. PMID- 1452398 TI - Effects of sodium valproate on the immune response. AB - The effects of long-term treatment with sodium valproate (VAL) on humoral immunity (Jerne plaque assay) and the delayed-type hypersensitivity (DTH) response of mice were studied. The resistance of treated animals to bacterial infection was also investigated. Various doses of sodium valproate were administered intraperitoneally (on alternate days) for periods of 1, 3 and 7 weeks. Although treatment for 1 week produced no significant effect, VAL treatment (50 and 150 mg/kg/48 h) for periods of 3 and 7 weeks resulted in enhanced numbers of plaque-forming cells (PFC) per spleen and increased spleen weights (after 3 weeks treatment). In contrast, VAL pretreatment of spleen cells in vitro was without effect. Also, no effect of VAL on DTH was observed after 1 or 3 weeks treatment (150 mg/kg/48 h). PMID- 1452399 TI - Anticomplementary activity of boswellic acids--an inhibitor of C3-convertase of the classical complement pathway. AB - Boswellic acids (BA), an anti-inflammatory and anti-arthritic principle/s of Boswellia serrata, were found to possess anticomplementary activity. It inhibits the in vitro immunohaemolysis of antibody-coated sheep erythrocytes by pooled guinea-pig serum. The reduced immunohaemolysis was found to be due to inhibition of C3-convertase of the classical complement pathway. The threshold concentration for inhibiting C3-convertase was found to be 100 micrograms. However, higher concentrations of BA showed constant inhibitory effects on immunohaemolysis. BA also exhibited weak inhibitory effects on individual components of the complement system. In vivo administration of BA also showed the inhibitory effect on guinea pig serum. PMID- 1452400 TI - Modification of spleen cell subsets by chronic cocaine administration and murine retrovirus infection in normal and protein-malnourished mice. AB - We have developed an experimental mouse model to study the effect of daily cocaine administration on the immune system during an acquired immune deficiency syndrome (AIDS). Mice were infected with LP-BM5 murine leukemia virus, a retrovirus which causes immunosuppression with the development of functional murine AIDS. Increasing doses of cocaine given by daily intraperitoneal injection for 11 weeks reduced body weight. A daily cocaine injection in some mice as well as a saline injection in others showed a decrease in the percentage of Thy 1.2+, CD4+ and CD8+ cells, while both treatments increased the percentage and absolute numbers of B-cells per spleen. Saline and cocaine treatment induced an increase in gamma-IFN and TNF-alpha production by splenocytes. Cocaine treatment favored a decrease in sIL-2R secretion. Saline and cocaine treatment had slightly different effects on the splenocytes of protein-malnourished mice. Cocaine treatment induced an increase in the percentage of CD8+ cells. Saline and cocaine treatments decreased the number of Mac 1+ cells in the spleen. Moreover, saline- and cocaine-treated protein-malnourished mice splenocytes did not present the increase in gamma-IFN production as well-nourished mice splenocytes showed. Retrovirus-infected mice showed a decrease in the percentage of Thy 1.2+ and CD8+ cells and an increase in the percentage and absolute numbers of CD4+, IL-2R+, Mac 1+ and B-cells. Cocaine partially prevented the enlargement of lymphoid organs due to lymphoid cell proliferation induced by murine retrovirus infection, but had little effect on the elevated percentage of CD4+ cells or B-cells or the depressed numbers of CD8+ cells associated with virus infection. However, cocaine did reduce the number of activated IL-2R+ cells and macrophages (Mac 1+) in addition to reducing the total number of cells per spleen in all subsets in retrovirus-infected mice, but not in uninfected controls. Cocaine treatment and retrovirus infection alone or in combination suppressed the release of sIL-2R into supernatant fluid during in vitro culture of splenocytes. These data illustrate that cocaine treatment modulates cell proliferation in retrovirus infected mice and thus modifies the absolute number of cells in those subsets already altered by retrovirus infection. Retrovirus-infected and retrovirus infected cocaine-treated protein-malnourished mice showed similar results. PMID- 1452401 TI - Drug-induced modulation of IL-2 production in experimental murine trypanosomiasis. AB - In this study we evaluated the effects of N-acetyl-cysteine and indomethacin in restoring IL-2 producing ability in vitro of splenocytes from mice infected with Trypanosoma equiperdum. Spleen cells from these mice were found to produce significantly lower levels of interleukin-2 (IL-2) in response to mitogen stimulation than spleen cells from uninfected control mice. This was accompanied by considerable suppression of IL-2-receptor expression, which was not attributable to the elimination of a particular T-cell subset. Impairment of IL-2 production was not due to a primary defect in L3T4+ T-cells, but rather to the presence of both adherent and non-adherent suppressor cells that apparently acted via prostaglandin-independent and dependent mechanisms. In fact, the IL-2 producing ability of lymphocytes from infected mice could be efficiently restored by in vitro exposure to N-acetyl-cysteine or indomethacin. PMID- 1452402 TI - Suppression of T-lymphocyte proliferation by sulphonamide hydroxylamines. AB - Hypersensitivity adverse drug reactions, characterized by fever and multi-organ involvement, are the most severe adverse reactions to sulphonamides. Although there is evidence that these reactions are initiated by metabolic events, these reactions appear to be propagated on an immune basis. We investigated the effect of a sulphonamide reactive metabolite, the hydroxylamine of sulphamethoxazole (SMX H/A), on the ability of T-lymphocytes to respond to stimulation with mitogens. Peripheral blood mononuclear cells (PBMCs) were collected and incubated with SMX H/A in increasing concentrations. PBMCs were then incubated with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) or with PHA and ionomycin. T-lymphocyte proliferation was then determined by tritiated thymidine uptake. The hydroxylamine of sulphamethoxazole produced a concentration-dependent decrease in T-lymphocyte proliferation; this decrease was significant even at concentrations of hydroxylamine that were not associated with a decrease in cell viability. PBMCs incubated with SMX H/A that were washed and then added to fresh PBMCs failed to inhibit the proliferation of fresh PBMCs. The hydroxylamine of sulfamethoxazole produces profound suppression of T-lymphocyte proliferation. This suppression appears to be a direct event and does not involve the activation of suppressor cells. These findings may explain the infectious complications contributing to mortality associated with sulphonamide hypersensitivity reactions. PMID- 1452403 TI - Selective inhibition of T-cell-dependent immune responses by bisbenzylisoquinoline alkaloids in vivo. AB - The bisbenzylisoquinoline (BBI) alkaloids, chondocurine, tetrandrine, isotetrandrine and cepharanthine, were tested for immunosuppressive activity in mice. A plaque-forming cell (PFC) response to a T-cell-dependent antigen, sheep red blood cell, was significantly suppressed by a 7 day treatment of chondocurine or tetrandrine at 1 mg/kg/day and of isotetrandrine at 50 mg/kg/day, but not suppressed by cepharanthine treatment. The suppressive effect of chondocurine was greater when it was given after immunization rather than before or concurrently. However, it did not affect the PFC response to a T-cell-independent antigen, lipopolysaccharide. A delayed-type hypersensitivity was also suppressed by chondocurine treatment. There was no significant change in lymphocyte number and proportion of T-cell subsets in the BBI alkaloid-treated mice. These data suggest that there is selective inhibition by chondocurine and tetrandrine of the T-cell dependent immune reactions. PMID- 1452404 TI - Immunomodulatory effects of neem (Azadirachta indica) oil. AB - Immunomodulatory effects of neem oil were studied in mice. The animals were treated intraperitoneally (i.p.) with neem oil; control animals received the emulsifying agent with or without peanut oil. Peritoneal lavage, collected on subsequent days, showed a maximum number of leukocytic cells on day 3 following treatment with neem oil; peritoneal macrophages exhibited enhanced phagocytic activity and expression of MHC class-II antigens. Neem oil treatment also induced the production of gamma interferon. Spleen cells of neem oil-treated animals showed a significantly higher lymphocyte proliferative response to in vitro challenge with Con A or tetanus toxoid (TT) than that of the controls. Pre treatment with neem oil, however, did not augment the anti-TT antibody response. The results of this study indicate that neem oil acts as a non-specific immunostimulant and that it selectively activates the cell-mediated immune (CMI) mechanisms to elicit an enhanced response to subsequent mitogenic or antigenic challenge. PMID- 1452405 TI - Immunotoxicity of subchronic versus chronic exposure to aldicarb in mice. AB - In this study we compared the immunotoxicity of subchronic vs chronic exposure to the aldicarb insecticide at a relatively low, 0.1-10 ppb, level in drinking water. The immunotoxicity of aldicarb was evaluated in 28- and 90-day studies by determination of the humoral, cellular and nonspecific immunity in inbred C57BL/6 mice. Quantification of splenic plaque-forming cells (PFC) to sheep erythrocytes (SRBC), mitogen activation of spleen lymphocytes, mixed lymphocyte reaction (MLR) and the cytofluorometric assay of the phagocytic uptake of fluorescent beads were among the parameters studied. Neither the cell viability nor the splenic cell count was affected by the insecticide exposure. Immunophenotyping and cytometric determination of L3T4+, Lyt2+ and Ig+ cells revealed no effect of the insecticide exposure on the total count of cell subsets in the ungated splenocyte population. However, a marked shift in the percentages of L3T4+ and Lyt2+ cells was noted after subchronic exposure to 1 and 10 ppb aldicarb, possibly indicating activation of these splenic T-cell subsets. Subchronic aldicarb exposure significantly suppressed the splenic PFC response to SRBC at 1 ppb dose, however, no dose-effect correlation could be concluded. Similarly, no dose-effect correlation was observed for subchronic aldicarb-related changes in mitogen responses. Subchronic exposure to aldicarb had no statistically significant effect on the mixed lymphocyte reaction (MLR) or on the macrophage phagocytosis. Chronic exposure to 0.1-10 ppb aldicarb did not affect any of the parameters measured, including the cell subsets. Thus, aldicarb-related changes in immune parameters, noted after a 28-day exposure, were compensated over chronic exposure to the insecticide. PMID- 1452406 TI - Cocaine augments proliferation of human peripheral blood T-lymphocytes activated with anti-CD3 antibody. AB - Previously we observed that cocaine can suppress the phytohemagglutinin-induced proliferation of cultured, purified human T-lymphocytes. However, because the receptor activation pathways stimulated by this mitogen are not fully understood, we decided in the present study to examine the effects of cocaine on T-lymphocyte cultures stimulated with the anti-CD3 antibody which is known to stimulate these cells through the T-cell receptor complex. The results show that cocaine augments T-lymphocyte proliferation to anti-CD3 stimulation at drug concentrations observed in the blood of cocaine abusers. This augmentation was dose dependent reaching a plateau at a concentration above 0.75 microM. The amount of interleukin-2 (IL-2), as measured by ELISA, in the supernatants of T-cell cultures and the level of cytosolic free-calcium (Ca2+) mobilization in the T cells were also increased at approximately the same concentrations that increased proliferation. Cocaine treatment alone had no effects on proliferation, IL-2 production, or Ca2+ mobilization. These results suggest that cocaine augments proliferation of human T-lymphocytes when the cells are activated through the T cell receptor complex by increasing cytosolic Ca2+ mobilization and subsequent IL 2 production. PMID- 1452407 TI - Effects of 2-mercaptoethanol and buthionine sulfoximine on cystine metabolism by and proliferation of mitogen-stimulated human and mouse lymphocytes. AB - Cysteine is an essential amino acid for lymphocytes and its anabolic products are intimately involved in lymphocyte activation. The purpose of this study was to assess the uptake and subsequent utilization of cyst(e)ine by mitogen-stimulated human peripheral blood mononuclear cells (PBMC), to evaluate the effect of an exogenous thiol, 2-mercaptoethanol (2ME), on these processes, and to compare human and mouse lymphocyte reactivities. Unlike mouse lymphocytes, the proliferation of human T-cells was inhibited by addition of 2ME although 2ME enhanced cystine uptake. Optimal responses to T-cell mitogens (Con A and PHA) were obtained with a cystine concentration of greater than or equal to 25 and 200 microM for human and mouse cells, respectively, and 2ME enhanced DNA synthesis of Con A-stimulated mouse cells regardless of the cystine dose; however, 2ME enhanced the response of human cells only in the presence of suboptimal doses of cystine. To assess whether 2ME's inability to enhance human PBMC responses was related to their glutathione (GSH) content, the human PBMC were pretreated with buthionine sulfoximine (BSO, an inhibitor of GSH synthesis). Even when the initial intracellular GSH concentration was lowered to below that of mouse lymphocytes, 2ME still inhibited proliferation. In contrast, addition of 2ME to human PBMC maintained in the presence of BSO enhanced the proliferative response suggesting that a critical level of thiols is needed for proliferation. The ability of 2ME to enhance proliferative responses in cystine deficient medium supports this contention. Consistent with thiol involvement in activation, Con A increased [35S]cystine uptake 2-fold within 4 h of incubation and enhanced subsequent conversion of cystine into cysteine and GSH. Interestingly, BSO treatment only slightly inhibited Con A-induced protein synthesis (5%), but it significantly suppressed conversion of cystine into cysteine or GSH (80-95%) and blocked DNA synthesis (90%). Overall, the results indicate that various differential thiol characteristics must exist between human and mouse lymphocytes and that a reducing equivalent is necessary for DNA synthesis but not lymphocyte activation. PMID- 1452408 TI - Normal development of lymphokine activated killing (LAK) in peripheral blood lymphocytes from hyperprolactinemic patients. AB - The effect of prolactin on the interleukin 2 (IL2)-driven development of Lymphokine Activated Killing (LAK) by normal PBL and by PBL from hyperprolactinemic patients was investigated. Concentrations of PRL corresponding to the physiological serum levels of the hormone and to the Kd of the PRL receptors on NK cells (6-20 ng/ml, 0.3-1 nM) had no effect on the generation of LAK activity by normal PBL, whereas 100-200 ng/ml were slightly, although significantly, inhibitory. By contrast, PBL from 16 hyperprolactinemic patients developed levels of LAK activity comparable with those generated by PBL from age- and sex-matched normoprolactinemic donors. PMID- 1452409 TI - Experimental model of autoimmune hemolytic anemia induced in mice with levodopa by intraperitoneal injection or oral feeding. AB - In this paper we describe a murine experimental model of autoimmune hemolytic anemia induced with multiple injections or oral feeding of levodopa. Strain A mice were intraperitoneally injected or fed with levodopa, at a dose equivalent to the one used in human therapy, and subsequently they developed cycles of IgM, IgG and IgA anti-mouse red blood cells (MRBC) autoantibody responses. Levodopa injection induced serum IgM and IgG anti-MRBC responses and levodopa feeding enhanced the serum anti-MRBC IgA response. The appearance of autoantibodies in the serum was followed by binding of the autoantibodies to mice erythrocytes and three phases of anemia. Red cell bound IgM and IgG autoantibodies were predominant in levodopa-injected mice whereas red cell bound IgA autoantibodies were predominant in levodopa-fed mice. The specificity of the serum IgA autoantibody was not restricted since it interacted with erythrocytes of various species. PMID- 1452410 TI - Potentiation of immune responses in mice by a new inosine derivative--methyl inosine monophosphate (MIMP). AB - Inosine 5'-methyl monophosphate (MIMP) is a new immunomodulator designed to improve upon the activity of other thymomimetic purines. In Balb/c mice, MIMP was assessed for toxicity and activity on immune responses. The lethal dose for half the mice (LD50) exceeded 500 mg/kg of body weight by both the parenteral and oral routes. At doses of 1-100 mg/kg, the mice showed no visible untoward effects. The antibody response of splenocytes to sheep erythrocytes (SRBC) was measured by IgM plaque-forming cells (PFC) in soft agar under optimal conditions of immunization and challenge. MIMP (1-100 mg/kg) was given by both the intraperitoneal and oral routes (gavage) at the time of SRBC injection and 4 days thereafter. The PFC response was found to be significantly augmented. The maximum effect (approximately 2x) was observed at 50 and 100 mg/kg, via intraperitoneal (i.p.) and oral routes, respectively. Increases (maximally 1.5x) in the responses of splenic lymphocytes to mitogen stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A) were observed under similar conditions of MIMP treatment. SRBC-induced delayed-hypersensitivity (DTH) was also measured under optimal conditions. By both i.p. and oral routes, enhancement of DTH response was produced by the lower doses of MIMP (0.01-1 mg/kg). Again, a second peak of optimum stimulation of DTH response was produced by 50 mg/kg of MIMP when administered by both routes. The effect was observed mainly on the sensitization rather than on the expression phase. MIMP qualifies as an effective immunopotentiator in normal mice. PMID- 1452411 TI - Identification of immunoreactive forms of thymosin alpha 1 in serum and supernatants by combining HPLC and RIA. AB - Thymosin alpha 1 (T alpha 1) is a biologically active peptide, originally isolated from the thymus and currently undergoing clinical trials as an immunomodulator in cancer patients, in individuals with chronic active hepatitis, and as an immunoenhancer of vaccines in immunocompromised individuals. Absorption of rabbit antibody to thymosin alpha 1 with a synthetic C-14 fragment of T alpha 1 results in an antiserum with increased affinity for the amino terminal region of T alpha 1 and the precursor protein prothymosin alpha (ProT alpha). Using HPLC methodologies, the predominant form of immunoreactivity in serum and thymus was T alpha 1 not the precursor. Using this assay we detected a decline in mouse serum T alpha 1 following irradiation but not thymectomy, an observation consistent with the existence of an important radiation sensitive lymphoid source of serum T alpha 1. The secretion of authentic T alpha 1 but not the precursor into culture medium by thymic epithelial cells as well as in mitogen-stimulated peripheral blood lymphocytes was also demonstrated by HPLC/RIA. HPLC analysis by molecular weight sizing columns demonstrated that unlike thymic epithelial cells or peripheral blood lymphocytes, the immunoreactive T alpha 1 (IRT alpha 1) form in the supernatants from tumor cells such as MCF-7 breast carcinoma was of a lower molecular weight than authentic T alpha 1. These studies suggest that the authentic form of T alpha 1 is the major immunoreactive form in normal serum and that it is secreted by the medullary thymic epithelial cells as well as by peripheral blood lymphocytes. An additional immunoreactive form, secreted by tumor cells has also been identified and is the subject of future studies. PMID- 1452412 TI - In vitro and ex vivo effect of tiaprofenic acid on human peripheral blood mononuclear cells. AB - The effect of the non-steroidal anti-inflammatory drug (NSAID) tiaprofenic acid on different human immune parameters was investigated in vitro or following in vivo administration in healthy adult volunteers. Results from the in vitro study demonstrated an increased mitogen-induced blastogenesis and interleukin 2 (IL-2) production together with a reduced polyclonal immunoglobulin (Ig) secretion in the presence of the drug. Results from the ex vivo study showed that treatment with tiaprofenic acid had no significant effects on the immune parameters investigated, i.e. unstimulated and mitogen-induced proliferation and IL-2 production, spontaneous and stimulated Ig synthesis, lymphocyte subpopulations, serum Ig and complement levels. PMID- 1452413 TI - Peptides and their constituent amino acids influence the immune response and phagocytosis in different ways. AB - To elucidate the role of immunoactive amino acids (which are capable of stimulating the immune response) in the peptide regulation of antibody production and phagocytic processes we have studied the influence of some fragments of natural peptides and the amino acids included in them on the thymus-dependent immune response to sheep red blood cells (SRBC) and on the phagocytosis of Staphylococcus by murine peritoneal neutrophils. It has been found that the effects of amino acids, as well as of peptides that they form, on the immune response and on phagocytosis were diverse. Glutamic and aspartic acids, threonine and valine stimulated both the immune response and phagocytosis. Glycine and isoleucine influenced neither the immune response nor phagocytosis, whereas lysine, proline, tyrosine and leucine did not influence the immune response, but enhanced the phagocytic activity of neutrophils. Arginine inhibited the immune response but stimulated phagocytosis. Peptide TTKD section (the fragment 77-80 of murine Thy-1-antigen) contained in C- and N-terminus amino acids (T and D) which stimulated the antibody production and phagocytosis, and lysine (K) which stimulated phagocytosis only, enhanced both processes. Peptides LGIP and PYIK (the fragments 49-53 and 66-69 of murine Thy-1 antigen) which contained both immunologically inert amino acids (L, G, I, P, Y, K) and phagocytosis stimulating amino acids (L, Y, P, K) influenced neither the immune response nor the phagocytic activity of neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452414 TI - Anti-CD3-induced T-cell activation in vivo--I. Flow cytometric analysis of dose responsive, time-dependent, and cyclosporin A-sensitive parameters of CD4+ and CD8+ cells from the draining lymph nodes of C57Bl/6 mice. AB - An in vivo model to assess the effects of chemicals on T-cell activation has been characterized and validated using the immunosuppressive drug, cyclosporin A (CsA). The dose response and kinetic effects of the hamster anti-mouse monoclonal antibody 145-2C11 (anti-CD3) on various parameters of T-cell activation were examined in cells from the draining popliteal and inguinal lymph nodes of C57Bl/6 mice. Parameters of anti-CD3-induced T-cell activation included 3H-TdR incorporation (+/- recombinant murine IL-2), and flow cytometric analysis of CD3 and IL-2 receptor (IL-2R) expression on CD4+ and CD8+ cells. Increases in the percentage of lymphocyte subsets in the S/G2M phase of the cell cycle and total cell recovery following anti-CD3 are also reported. Increased 3H-TdR incorporation was maximal over a dose range of 0.25-25 micrograms anti-CD3, while maximal increases in the percentage of CD4+ and CD8+ cycling occurred after a dose of 2.5 micrograms anti-CD3. At 24 h after anti-CD3 treatment, CD3 expression on both CD4+ and CD8+ cells was dose dependently down-modulated while IL-2R expression and IL-2-driven 3H-TdR incorporation were dose dependently increased. In addition, total cell recovery increased at 24 h and correlated with an increase in the percentage of B220+ cells present in the lymph nodes. There was a corresponding decrease in the percentage of Thy 1.2+, CD4+, and CD8+ cells. No increase in cycling of B220+ cells was observed, suggesting an influx of B220+ cells into the node rather than proliferation. Elevation in 3H-TdR incorporation occurred as early as 4 h after anti-CD3 treatment, while increases in the percentage of CD4+ and CD8+ cells cycling were not apparent until 24 h. At 48 h, the percentage of CD8+ cells cycling doubled while the percentage of CD4+ cells cycling remained constant. Down-modulation of CD3 expression on CD4+ and CD8+ cells was apparent as early as 1 h after treatment with less than 10% of CD4+ and CD8+ cells expressing CD3 by 12 h. Induction of IL-2R expression and IL-2-driven 3H-TdR incorporation was maximal at 12 h after anti-CD3. The immunosuppressive drug, CsA (25, 50, or 100 mg/kg, i.p.) decreased anti-CD3-induced 3H-TdR incorporation. Concurrently, anti-CD3-induced increases in the percentage of CD4+ and CD8+ cells cycling were inhibited by CsA. Likewise, IL-2 responsiveness and IL-2R expression on both T-cell subsets were inhibited by CsA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1452415 TI - Macular oedema and retinal neovascularisation in juvenile diabetics. AB - Thirteen young diabetic patients with peripheral capillary non perfusion who presented with symptoms of mild maculopathy were reviewed retrospectively. In this group, peripheral retinal ischaemia was often overlooked and a rapidly progressive proliferative retinopathy developed. Fluorescein angiography of the peripheral retina showed capillary closure, but with preservation of arterioles and venules. In this series, half of the eyes lost vision. In seven eyes where the peripheral ischaemia was treated by pan retinal photocoagulation, the maculopathy resolved without any specific laser treatment to the macula. In young diabetics presenting with maculopathy, the peripheral retina should be examined for ischaemia, and if present, pan retinal laser photocoagulation should be performed. Focal treatment for the macular disease can be delayed until after the peripheral photocoagulation, as the maculopathy may remit. PMID- 1452416 TI - Xerophthalmia clinics in rural eye camps. AB - Even though the primary prevention of many eye diseases can be effectively incorporated into the existing pattern of rural eye camps, efforts in this direction are restrained and insubstantial. We describe our technique and experience in the prevention of xerophthalmia by organising a distinct entity called a xerophthalmia clinic in our eye camps. The clinic consists of an Ophthalmologist or an Ophthalmic assistant who will exclusively examine children who come to the eye camp. This is perhaps, the first report on rural xerophthalmia clinics, in ophthalmic literature. Over a seven year period from 1984 to 1990 we have conducted 71 xerophthalmia clinics amongst the ninty eye camps organised. A total of 11,370 children were examined in the xerophthalmia clinic out of which 18.9% were afflicted with the disease. Therapeutic doses of Vitamin A were administered on the spot to the afflicted and prophylactic doses were administered to the rest. Intensive health education efforts are made through clinics to effectuate change in dietry habits towards consumption of locally grown DGLV (Dark Green Leafy Vegetables) like Anthenum, chenopodium and Amaranthus. A bipronged offensive consisting of mega-dosing and health education is, for the present and the foreseeable future, the best strategy to combat xerophthalmia in this desert region. A year by year breakdown of prevalence rates in the present study shows that in years of severe drought the prevalence of xerophthalmia increases three fold over the non-drought or mild drought years, thereby demonstrating that drought is a substantial risk factor in developing countries leading to vitamin A deficiency and xerophthalmia. PMID- 1452417 TI - Anti-retinal S-antigen antibodies in human sera: a comparison of reactivity in ELISA with human or bovine S-antigen. AB - Various studies have demonstrated anti-retinal S-antigen (S-ag) antibodies in uveitis sera in assays using bovine S-ag. Because of its molecular similarity and cross-reactivity with human S-ag, reactions with bovine S-ag have been considered a reliable indication of anti-S-ag autoimmunity. To test this assumption, the cross-reactivity of purified human and bovine S-ags was quantitated by ELISA titration of various anti-human and anti-bovine S-ag immune reagents raised in mice, rats and rabbits. Anti-human S-ag reagents appeared to be largely cross reactive with bovine S-ag, whereas anti-bovine S-ag reagents were 6-10 times less reactive with the cross-reacting human S-ag than with bovine S-ag, thus showing a predominant role of species-specific epitopes on bovine S-ag. Furthermore, a large number of human control and uveitis sera was tested in ELISA with both human S-ag- and bovine S-ag-coated microwells. Both the numbers of positive sera and the levels of anti-S-ag antibodies in the two tests significantly correlated, but many exceptions were found, and the predictive value of reactions with bovine S-ag for the presence and levels of anti-S-ag autoantibodies was low. For individual human sera, assessment of anti-S-ag autoantibodies requires the use of human S-ag in immunoassays. PMID- 1452418 TI - Retinal toxicity of intravitreal lazaroid (21-aminosteroid U75412E). AB - The 21-aminosteroids or lazaroids are a novel series of compounds being developed for the acute treatment of traumatic or ischemic injury of the nervous system. These compounds were specifically designed to localize within cell membranes and inhibit lipid peroxidation reactions. In this study, 21-aminosteroid U75412E was injected into the vitreous body of rabbit eyes to evaluate its suitability for intraocular injection and its toxicity on intraocular tissues. Doses ranged from 20 micrograms to 200 micrograms. Retinal toxicity was determined through light and transmission electron microscopy and electroretinography. No retinal toxicity was noted in doses of 30 micrograms and below. PMID- 1452419 TI - Ocular involvement in acute lymphoblastic leukemia: an echographic study. AB - We report a case of acute lymphoblastic leukemia (ALL) with ocular involvement in which bilateral swelling of the optic disk head was noticed. Massive direct infiltration of the optic nerve head by leukemic cells can give rise to a clinical picture identical to that of a true papilledema. Ocular echography allowed a better and more complete interpretation of the optic disk involvement. No echographic description of a leukemic infiltration of the optic nerve head has been reported previously. PMID- 1452420 TI - Postural behaviour of intraocular pressure following trabeculoplasty. AB - Postural behaviour of intraocular pressure (IOP) was studied in 29 glaucomatous eyes before and after argon laser trabeculoplasty (ALT) and compared with that of 60 normal eyes. Although argon laser trabeculoplasty was successful in lowering the IOP below 21 mm Hg, it produced little effect on the postural behaviour of the IOP. No significant change was observed in the amplitude of postural rise of IOP in ALT treated eyes. PMID- 1452421 TI - Biophysical characteristics of the Meibomian lipid layer under in vitro conditions. AB - The biophysical behaviour of the Meibomian gland secretion was tested under in vitro conditions. Thereby, simultaneous recording of surface pressure and surface potential was performed. The Meibomian lipid layer was compared with other surface-active components like polyvinylalcohol and polyvinylpyrrolidone. On the other hand, Eledoisin was tested as an example for a surface-inactive substance. An attempt was made to describe the biophysical interaction between a given artificial tear substitute and the Meibomian lipid layer. With respect to the surface potential Dipalmitoyl-phosphatidyl-choline was established as an analogue for Meibomian gland secretion. Fluorescence measurements in the presence of a cyanine dye (1 N,N'dioctadecyloxacarbocyanine) were used as a method to localize the site of the characteristic potential change. From the fluorescence spectra under compression we conclude that the molecular change takes place at the lipid subphase interface of the Meibomian lipid layer. PMID- 1452422 TI - Astigmatism following cataract surgery: comparison of a scleral and a corneal incision in a mixed group of patients with and without glaucoma. AB - We retrospectively analysed the course of postoperative corneal astigmatism and corrected visual acuity after extracapsular cataract extraction and posterior chamber lens implantation with either a corneal or a scleral incision in 170 eyes of 155 patients with and without glaucoma. A continuous 10/0 nylon shoelace suture was used for wound closure in two groups. In a third group, corneal wound closure was performed with a shorter shoelace suture in combination with two vicryl wing sutures at 11 and 1 o'clock. Although early postoperative mean astigmatism in eyes operated through a corneal incision was high (range 2.92-6.67 diopters at 1 month postoperatively) and significantly different when compared to eyes operated through a scleral incision (1.96 diopters), final mean astigmatism did not differ significantly between those two groups. Moreover, in 27% of eyes operated through a corneal incision, mean astigmatism at 2 months postoperatively was not significantly different from the scleral group and suture removal was not necessary. There was no statistically significant difference in corrected visual acuity over the entire study period between groups. Since safety and functional results of the corneal incision were not different from the scleral incision, we prefer a corneal incision in cataract surgery because of its surgical advantages, especially in patients with cataract and coexisting glaucoma. PMID- 1452423 TI - Berson test for blue cone monochromatism. AB - The Berson test for blue cone monochromatism discriminates X-linked blue cone monochromatism from achromatopsia but not from X-linked progressive c dystrophy. PMID- 1452424 TI - Rhodotorula glutinis keratitis. PMID- 1452425 TI - Anterior segment photography using the Oxford retro-illumination camera. AB - The use of the Oxford retro-illumination camera in documenting cataract is now well established. Repeatability has been shown to be good. This article describes its use in photographing the anterior segment of the eye. PMID- 1452426 TI - A 'tent trabeculectomy' (T.T)--surgical alternative for countries of the Third World. PMID- 1452428 TI - Calcium and mitosis. PMID- 1452427 TI - Photoreceptor rescue in the dystrophic retina by transplantation of retinal pigment epithelium. PMID- 1452429 TI - Polyamine cytochemistry: localization and possible functions of polyamines. PMID- 1452430 TI - Mitochondrial genomes of the ciliates. PMID- 1452431 TI - Animal mitochondrial DNA: structure and evolution. PMID- 1452432 TI - Transcription and replication of animal mitochondrial DNAs. AB - The development of in vitro transcription and replication systems has allowed the identification of promoter sequences and origins of replication for several animal mtDNAs. As a consequence, the necessary reagents and basic information are available to permit the characterization of transacting factors that are required for transcription and replication. All of the animal trans-acting species purified at this time are known or reasoned to be nuclear gene products. There is now the opportunity to learn how these nuclear genes are regulated and the mechanisms that are utilized for the import of their products into the organelle. With regard to import, the human transcription factor mtTF1 appears to have an amino-terminal sequence characteristic of other imported mitochondrial proteins (Parisi and Clayton, 1991). An interesting issue is the degree to which fundamental features of mtDNA replication and transcription are conserved between species. With regard to animal mtDNAs, there is very little in the way of conservation of DNA sequence at the promoters and origins of replication. The exceptions to this are the presence of a characteristic stem-loop L-strand origin of replication sequence in vertebrates [except for chicken mtDNA (Desjardins and Morais, 1990)] and the general presence of CSBs II and III (and to a lesser extent CSB I) in most higher animal mtDNAs. Because mtDNA promoters are not highly conserved, it is perhaps not surprising that general cross-species transcription does not occur, except for very limited examples of closely related species and sequences (Chang et al., 1985b). Using crude mtRNA polymerase holoenzyme preparations, there is no specific transcriptional initiation when proteins from human mitochondria are used with mouse mtDNA promoter templates, and vice versa. However, in contrast to this overall observation, purified fractions of human or mouse mtTF1 can be exchanged and shown to function across species boundaries (Fisher et al., 1989). The ability of mitochondrial mtTF1-type proteins to operate across even greater evolutionary distances was suggested by the ability of human and yeast proteins to recognize some mitochondrial promoter sequences in common (Fisher et al., 1992). More recent studies suggest that human mtTF1 can substitute for its yeast homolog in vivo, and thereby perform at least the most critical functions required to maintain yeast mtDNA in the cell (M.A. Parisi, B. Xu, and D.A. Clayton, submitted for publication). The other sites of conserved macromolecular interactions are related to the two origins of DNA replication.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1452433 TI - The endosymbiont hypothesis revisited. PMID- 1452434 TI - Evolution of mitochondrial genomes in fungi. PMID- 1452435 TI - A review of the nature and activity of a general surgical service in Ireland. AB - The steady increase in hospital costs has led to demands for closer scrutiny of activity levels, workloads and outcomes. This study sought to examine these parameters in a typical district general surgical unit in this country. In the five year period 1985-89, 11,227 inpatient and 3,354 outpatient procedures were performed; 83% of the inpatient procedures were elective and 17% were emergency surgical operations. All inpatient procedures were categorized: minor (41%), intermediate (42%) and major (17%). A prospective one year review in 1990/1991 confirmed the accuracy of the retrospective data. During that year 2,335 inpatient operations and 765 outpatient operations were performed, of which 80.5% of the inpatient operations were elective and 19.5% were emergency procedures. Of these 16.6% were major, 34.4% intermediate and 49% were minor operations. 60% of the operations were performed by consultants. The in-hospital surgical mortality for the 1 year prospective review was 1.35% and the perioperative mortality was 0.64%. The overall operation morbidity rate was 9% and the procedure-related morbidity was 4.7%. The wound infection rate was 2%. Of the common operations performed throughout the six year study period appendicectomies and external hernia operations accounted for 20% of the caseload; 14% were urological, 7% were breast and 6% were biliary operations. The average waiting time for elective admissions was less than 4 weeks. The average length of hospital stay and the bed occupancy rates did not change. PMID- 1452436 TI - Contemporary risk factors for sudden infant death in an Irish population--a case control study. AB - This case-controlled study examines some recently implicated risk factors for Sudden Infant Death Syndrome (S.I.D.S.) in Irish infants. Irish S.I.D.S. infants are lighter at birth than controls (3463g) compared to (3542g) and boys out number girls by a ratio of 1.3:1. S.I.D.S. infants are more frequently: breast fed (42% vs 25%) and sleep in a location other than the parent's bedroom (54% vs 21%), but start solids at a similar age and appear not to be sicker prior to death than the control group. This study highlights the frequency of symptoms of possible ill-health (i.e. snuffles and being "chesty") in well infants during the first months of life with 32% of the control group having snuffles and 35% described as "chesty". In addition these symptoms are frequently treated with antibiotics with 31% of the control group having already received antibiotics by 2 months of age. A majority of S.I.D.S. infants were described as cold when found (52%) with 39% described as warm and 15% as sweaty. Obviously the recently implicated role of overheating may be relevant in the latter 15% of S.I.D.S. cases. In this series, 88% of infants had died by 6 months of age. Of the 97 parents of S.I.D.S. infants questioned, 78 had subsequently become pregnant by the time the study was conducted at an average time of 5 months post the S.I.D.S. event. PMID- 1452437 TI - The correlation between clinical diagnosis of knee pathology and findings at arthroscopy. AB - 175 patients referred for arthroscopy were studied prospectively to assess the accuracy of clinical examination supplemented by standard radiology in the evaluation of knee symptoms. Clinical diagnosis of medial meniscal tears was inaccurate while greater confidence could be placed in the diagnosis of anterior cruciate ligament and lateral meniscus tears. Clinical accuracy rates could be improved if patients with minimal symptoms were excluded from arthroscopy examination. PMID- 1452438 TI - Hyperthyroidism associated with acute suppurative thyroiditis. AB - Acute suppurative thyroiditis is a rare condition with potentially serious complications. It has been suggested that hyperthyroidism may be a feature in occasional cases but this has been poorly documented. We describe a patient in whom acute suppurative thyroiditis caused transient hyperthyroidism. PMID- 1452439 TI - Colo-rectal carcinoma 1975 and 1990: no improvement in the stage of disease at resection. AB - There is no overall consensus as to what screening patterns should be adopted for individuals of average risk for colo-rectal carcinoma. The single most important prognostic factor in survival is the stage of the colo-rectal neoplasm at the time of resection. Consequently significant resources have been directed to early detection while the disease is at a curative stage. To assess the impact of widespread availability of faecal occult blood testing and large bowel endoscopy we prospectively examined all large intestine specimens resected for carcinoma in 1990 and compared them with specimens resected for colonic carcinoma in 1975. We excluded adenomatous polyps with malignant change which had been treated by snaring at colonoscopy, without subsequent colectomy, as their precise Duke's staging was so difficult. In any event, their numbers were small (> 5 in 1990). Our study shows that despite the resources targeted at early diagnosis of colo rectal carcinoma resection of tumours at a prognostically favourable stage has not been improved in the 25 years since 1975. PMID- 1452440 TI - Irish Cardiac Society. Annual general meeting. Galway, 8-9 November 1991. Abstracts. PMID- 1452441 TI - Cd-metallothionein in liver and kidney of goldfish (Carassius auratus): effects of temperature and salinity. AB - Treatment of goldfish with Cd, by intraperitoneal injection, resulted in Cd metallothionein (Cd-MT) synthesis mainly in liver and kidney. The relative amount of Cd sequestered by liver metallothionein was always greater in fish maintained at 20 degrees C compared to those reared at 10 degrees C, indicating a temperature dependence of metallothionein biosynthesis; in the kidney this dependence was not so clearly evident. Changes in MT levels induced by adapting fish to different salinities did not correlate with the salinity change. PMID- 1452442 TI - In vivo treatment with a monoclonal antibody to interferon-gamma neither affects the survival nor the incidence of lupus-nephritis in the MRL/lpr-lpr mouse. AB - The effects of the in vitro treatment with a mAb (DB-1) that neutralizes mouse IFN-gamma on the development of the SLE-like syndrome in MRL/lpr-lpr (MRL-lpr) mice were studied. The results show that the i.p. administration of 2.6 mg/week of DB-1 from the 12th to the 20th week of age neither affected the survival nor the incidence and severity of lupus nephritis in MRL-lpr mice. This study argues against the pathogenic relevance of IFN-gamma in this experimental model of human SLE. PMID- 1452443 TI - Mitogenic activities of heteroglycan and heteroglycan-protein fractions from culture medium of Lentinus edodes mycelia. AB - The water soluble material (LEM) was prepared from the solid culture medium in which Lentinus edodes mycelia were growing actively. An alcohol insoluble material was prepared from LEM and subjected to Sepharose 6B gel filtration. The void fraction (LAP1) was composed mainly of xylose-rich heteroglycan and protein. From LAP1, a heteroglycan fraction (LAF1) was prepared by DEAE-Sepharose CL-6B column chromatography. LAP1 and LAF1 enhanced the incorporation of [3H]thymidine into mouse splenic cells (SPs). At each of the optimum doses, the rate of the incorporation was about 10 times as high with LAF1 as with LAP1. Such mitogenic responses were not induced in nylon-column effluent SPs and thymocytes. sIg expressed cells were responsive to LAF1, but not to LAP1. Moreover, with each fraction, the incorporation was enhanced more in plastic adherent splenic cells (ADs) than in SPs. The flow cytometric assay revealed that the number of Mac-1+ cells is about 13 times as many in ADs as in SPs and that the number of Ly-5+ or Thy-1.2+ cells is considerably reduced in ADs compared with that in SPs. Thus, the present studies suggest that LAP1 and LAF1 act as mitogens predominantly for mouse splenic macrophages and/or monocytes. PMID- 1452444 TI - Subtractive antibody to a human immunosuppressive lymphokine affinity isolates a suppressive factor and blocks its function. AB - Hybridoma suppressor factor(s) (HSF), secreted by a human thymus hybridoma (8E 24) established in this laboratory, suppresses Ig as well as IL-2 synthesis by peripheral blood mononuclear cells (PBMC). To aid in the characterization of this lymphokine, we prepared a subtractive antibody to HSF using the products of the hybridoma parent cell line to generate antibodies to irrelevant proteins. The concentrated supernatant fluid of the hybridoma parent cell line (CEM) was used to generate rabbit antibodies and titers of anti-CEM were monitored by enzyme immunoassay (EIA). Next, to remove factors shared by both the parent cell line and hybridoma, the concentrated supernatant fluid of 8E-24 (crude HSF) was passed over an immunoaffinity column, composed of protein A beads coupled to anti-CEM. The 'subtracted' HSF, termed partially purified HSF, was shown to be suppressive in vitro and was then used to prepare a second rabbit antisera. Using partially purified HSF as antigen, the presence of specific antibody was monitored by EIA. This antibody (anti-HSF) was used to prepare another immunoaffinity column by covalently coupling this antibody to protein A beads. Factors bound and then eluted from this affinity column were shown to inhibit IL-2 production by PBMC in a manner similar to HSF. Specific activity of the affinity purified HSF was 50 times that of partially purified HSF. Furthermore, the suppressive activity of affinity purified HSF was abrogated in the presence of anti-HSF. Western blot analysis performed on the concentrated crude HSF, using both the anti-HSF and anti-CEM antibodies, revealed the presence of several bands that selectively reacted with anti-HSF and not anti-CEM. Each of these bands were present in the affinity purified HSF. Of particular interest due to their similar size to the suppressive agent are a band at 12 kDa that reacts selectively with anti-HSF and is detected in crude and affinity purified HSF and a band at 10 kDa. In summary, this protocol resulted in the detection and separation of hybridoma specific proteins within the predicted size range of the suppressive lymphokine. PMID- 1452445 TI - The role of designated driver programs in the prevention of alcohol-impaired driving: a critical reassessment. AB - We review the "designated driver" concept and the current debate over its role in preventing alcohol-impaired driving. In our view, the focus on this strategy by broadcasters, the alcohol industry, and various public service groups has deflected attention from other alcohol-related problems that account for the vast majority of deaths and injuries associated with alcohol use. This focus has also distracted many public health advocates and policymakers from the bigger and more important jobs of increasing public awareness of the social, environmental, and economic factors that influence alcohol consumption and promoting debate on legislation and other public policy solutions to alcohol-impaired driving. As part of a comprehensive strategy, we strongly encourage a renewed focus on "sobriety checkpoints," strict enforcement of laws against alcohol sales to minors, alcohol advertising reform, increased excise taxes, and other public policy initiatives supported by the Surgeon General. These measures will curb underage and heavy alcohol consumption and will create a legal and social environment in which individuals are motivated to avoid impaired driving through several alternative strategies, including but not limited to the use of designated drivers. PMID- 1452446 TI - Mammography usage and the health belief model. AB - Regular screening mammograms for asymptomatic women are the most effective method for early detection of breast cancer. This study assessed the relative influence of Health Belief Model (HBM) constructs on prior mammography usage and the intention to obtain mammograms with data from a sample of 1,057 women over the age of 35 years residing in an urban community in the United States. Covariance structure analysis with latent variables was used initially to perform a confirmatory factor analysis of indicators of Socioeconomic Status (SES), Perceived Susceptibility, Perceived Barriers, Perceived Benefits, Cues to Action, Prior Mammography, and Future Intentions. Once a plausible factor structure was confirmed, a predictive path model was tested with Future Intentions and Prior Mammography as the outcome variables. Cues to Action, operationalized as a physician influence variable, particularly impacted Prior Mammography, and Perceived Susceptibility was the most powerful predictor of Future Intentions. SES only related significantly to Perceived Barriers, and Cues to Action, and did not directly influence Prior Mammography and Future Intentions. HBM predictor variables alone accounted for the relationship between previous mammography experience and intentions to obtain mammograms in the future. Health education implications and an applied outreach program are discussed. PMID- 1452447 TI - A three-year evaluation of the know your body program in inner-city schoolchildren. AB - The impact of the Know Your Body (KYB) comprehensive school health education program was evaluated in a sample of first through sixth-grade students from New York City, using two analytic strategies: a longitudinal cohort and a "posttest only" cohort. In both cohorts, program impact was examined between condition (i.e., KYB vs. no-treatment comparison group) as well as within condition (i.e., low, moderate, and high student exposure). Students in the longitudinal cohort (n = 1,209) who were exposed to high implementation teachers had significantly (p < .05) lower total plasma cholesterol and systolic blood pressure at 3-year posttest than comparison students. Students in the posttest only cohort (n = 3,066) who had high implementation teachers showed significantly (p < .05) lower total plasma cholesterol, systolic blood pressure, self-reported intake of meat and desserts, as well as higher health knowledge and self-reported intake of "heart healthy" foods and vegetables than comparison students. In both cohorts, program effects for several outcome variables were linearly related to level of student exposure to the curriculum, suggesting a dose-response effect. While several methodologic limitations may have influenced study outcomes, these data nonetheless appear to confirm that the KYB program can have a significant positive impact on the knowledge, behavior, and selected risk factors of students in primary grades and that efforts to disseminate and evaluate school health education programs should include strategies to monitor and enhance teacher implementation. PMID- 1452448 TI - Patient attitudes concerning health behaviors during pregnancy: initial development of a questionnaire. AB - The major determinant of infant mortality in the United States is low birthweight (LBW). Health behaviors related to LBW are inadequate prenatal care, poor nutrition, smoking, and moderate to heavy alcohol use. Before interventions can be designed to assist women in modifying these health behaviors, more must be understood about their causes. The Health Belief Model (HBM) is a framework for analyzing beliefs that motivate health behaviors and is well established as a model for understanding health behavior decisions. The chief aim of this study was to develop an instrument to assess women's health beliefs during pregnancy. Questions for the instrument were generated around the four major constructs of the HBM: perceived susceptibility, seriousness, benefits, and barriers. Four focus group interviews, a literature review, and consultation with an HBM expert provided content for questions. The questionnaire was administered to a convenience sample of 127 women. The measurement models were tested using confirmatory factor analysis. Parsimony was achieved by reducing the original 106 item scale to 64 items. The final instrument provides support for the HBM but not for all of its discrete constructs. PMID- 1452449 TI - The impact of tailored self-help smoking cessation guides on young mothers. AB - It has been suggested that tailoring self-help materials for specific target populations will increase their effectiveness. This study tested the value of a self-help guide tailored specifically for women with young children. These women were recruited through a media campaign that encouraged smokers to call the Cancer Information Service (CIS) for assistance in stopping smoking. Women smokers with young children (under the age of 6) who called the CIS were given telephone counseling on quitting and were mailed one of three stop smoking guides. One third of callers received Quitting Times, a guide written specifically for women with young children; one third received the American Lung Association guide, Freedom from Smoking for You and Your Family; and one third received Clearing the Air, a guide developed by the National Cancer Institute. Six months after calling the CIS, these women were contacted by telephone to assess changes in smoking behavior. Overall, 12.5% of the women reported not smoking for at least 1 week at the time of the 6-month follow-up interview. There were no significant differences between subjects in the three groups in use of the self-help guides, methods used to attempt quitting, and quitting behavior. Findings from this study do not support the hypothesis that using a tailored stop smoking guide increases the targeted audience's cessation rate or affects quitting-related behavior. However, it should be noted that the smokers who called were predominantly in the contemplation or action stages. PMID- 1452450 TI - Morphological heterogeneity of secretory granules of rat Clara cells: an immunocytochemical study. AB - The secretory granules of rat bronchiolar Clara cells were classified into different types by their ultrastructural appearances followed by immunocytochemistry using anti-rat 10 kDa Clara cell-specific protein (10 kDa CCSP) antibody. One predominant type was the oval to round granule (type A granule), of which the matrix was composed of a map-like mixture of electron dense and less electron-dense material. Another predominant type was the rod shaped granule (type B granule). The content of type B granules varied from a finely fibrillar (type B1 granule) to an electron-dense, rod-like (type B3 granule) structure. Various intermediate types (type B2 granule) between type B1 and B3 granules were also found. Small cytoplasmic vesicles were found occasionally in close proximity to type B2 or B3 granule. Another type of granule (type C granule) was large, up to 8 microns in diameter, and contained a moderately electron-dense amorphous matrix. Both type A and C granules stained at a similar density with the antibody. The nascent form of type A granules, which was found in the vicinity to the trans face of the Golgi apparatus, was also labeled. On the other hand, the labeling density of type B granules varied: type B1 granules were almost devoid of immunolabeling, whereas type B3 granules were intensely labeled. Type B2 granules stained with the antibody; however, the labeling density was less than that of type B3 granules. The small cytoplasmic vesicles of type B2 granules were labeled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452451 TI - Comparative lectin histochemistry on taste buds in foliate, circumvallate and fungiform papillae of the rabbit tongue. AB - Taste buds (TB) in the foliate, circumvallate and fungiform papillae of the rabbit tongue were examined with lectin histochemistry by means of light (LM) and electron (EM) microscopy. Biotin- and gold-labeled lectins were used for the detection of carbohydrate residues in TB cells and subcutaneous salivary glands. At the LM level, the lectins of soybean (SBA) and peanut (PNA) react with material of the foliate and circumvallate taste pores only after pretreatment of the section with neuraminidase. This indicates that the terminal trisaccharide sequences are as follows: Sialic acid-Gal-GalNAc in O-glycosylated glycoproteins or Sialic acid-Gal-GlcNAc in N-glycosylated glycoproteins. In fungi-form taste buds the lectins of Dolichos biflorus (DBA) and Helix pomatia (HPA), also specific to GalNAc residues, are reactive without preincubation with neuraminidase. Wheat germ agglutinin (WGA), specific to GlcNAc, reacts with TBs of all papillae; and the lectin from Ulex europaeus (UEA I), specific to fucose, binds to individual TB cells. The presence of sialic acid may protect mucus or other glycoproteins in TB cells and inside the taste pore from premature enzymatic degradation. In a post-embedding EM procedure on LR-White-embedded tissue sections, only gold-labeled HPA was found to bind especially on membrane surfaces of the microvilli which protrude into the taste pore; however HPA did not bind to the electron-dense mucus inside the taste pore. The mucus situated in the trough and at the top of the adjacent epithelial cells also is strongly HPA positive, but is of different origin and composition than that found in the taste pore. These results demonstrate distinct carbohydrate histochemical differences between fungiform and circumvallate/foliate taste buds. The different configuration of galactosyl residues and the occurrence of mannose in circumvallate and foliate TBs leads to the suggestion that the lectin reactivities of TBs are not only due to the presence of mucins, but also to N linked glycoproteins, possibly with a hormone-like paraneuronal function. A possible relationship to v. Ebner glands in these papillae is discussed. PMID- 1452453 TI - Case report. Maxillofacial injury. PMID- 1452452 TI - Bromodeoxyuridine (BrdU) immunocytochemistry by exonuclease III (Exo III) digestion. AB - A new procedure is described to generate single-stranded DNA by exonuclease III (Exo III) digestion for bromodeoxyuridine (BrdU) immunocytochemistry on tissue sections. We compared this procedure with the most widely used procedure of DNA denaturation with 2 N HCl. In vivo and in vitro pulse and continuous labelling of tissues and cells were used. The specimens were fixed in formalin, ethanol, glutaraldehyde, Carnoy's, Bouin's or Zamboni's fixative and embedded in paraffin or used unfixed as cryostat sections or cytospin preparations. After Exo III digestion, BrdU substituted DNA was detected irrespective of the fixation procedure applied. The optimal protocol for nuclease digestion appeared to be simultaneous incubation, of 10 Units Exo III per ml EcoRI buffer and anti-BrdU monoclonal antibody at 37 degrees C. The advantages of Exo III digestion for BrdU immunocytochemistry compared to acid denaturation were: less non-specific nuclear background reactivity, no DNA renaturation, less DNA loss, optimal nuclear morphology, increase in antibody efficiency and the possibility for simultaneous detection of acid-sensitive tissue constituents. Disadvantages of the Exo III digestion are decreased sensitivity and the need for more rigorous pepsin pretreatment. We conclude that Exo III digestion of DNA is an appropriate alternative for acid denaturation for BrdU immunocytochemistry on sections of pulse-labelled specimens. PMID- 1452455 TI - Atrophic gastritis and stomach cancer risk: cross-sectional analyses. AB - The relationship between atrophic gastritis and stomach cancer risk was investigated in case-control analyses involving 387 cases with stomach cancer and 5,422 control subjects who received gastroscopic examination at Aichi Cancer Center Hospital from April, 1985 to March, 1989. The presence of atrophic gastritis, the degree and extension of the atrophy and the presence of granularity and erosion were diagnosed endoscopically by six gastroenterologists. The prevalence of atrophic gastritis increased with age and was higher in males than in females. The relative risk (RR) of stomach cancer was 5.13 (95% confidence interval (CI): 2.79-9.42) if a subject had any type of atrophic gastritis. The risk further increased with advancing degree of atrophy and increasing extension on the greater and lesser curvatures. The RR associated with severe atrophy was 7.73 (95% CI: 3.95-15.12). These associations remained significant when analyzed by sex and age. The presence of granularity and erosion did not much affect the estimated risks. A clear difference in risk appeared in the analyses by histological type of cancer. The RR associated with atrophic gastritis was 24.71 (95% CI: 3.46-176.68) for the intestinal type and 3.49 (95% CI: 1.77-6.87) for the diffuse type. These findings may suggest a need for intensive follow-up of patients with severe atrophic gastritis. PMID- 1452454 TI - Adduct formation at C-8 of guanine on in vitro reaction of the ultimate form of 2 amino-1-methyl-6-phenylimidazo[4,5-b]pyridine with 2'-deoxyguanosine and its phosphate esters. AB - We examined the reactivity of the N-hydroxyamino derivative of a carcinogenic heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), after its O-acetylation with four 2'-deoxyribonucleoside 3'-monophosphates. 32P Postlabeling analysis demonstrated that the levels of adducts with 2' deoxyguanosine 3'-monophosphate were much higher than those with the other three nucleotides. 1H-NMR, mass spectral and UV absorption spectral analyses of the major adducts formed by N-acetyoxy-PhIP with 2'-deoxyguanosine and with its phosphate esters indicated that PhIP bound at the C-8 position of guanine, as previously demonstrated with other heterocyclic amines. PMID- 1452456 TI - Species difference among experimental rodents in induction of P450IA family enzymes by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. AB - Rats, mice, hamsters and guinea pigs were given an i.p. injection of 2-amino-1 methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP), a protein-derived pyrolysate component present in cooked foods, and inductions of cytochrome P450 (P450) in the liver and kidney of these animals were examined. The activity and amount of P450s corresponding to the rat P450IA1 and P450IA2 were assessed by means of a bacterial mutation test using 3 carcinogenic heterocyclic aromatic amines including PhIP as substrates and by Western blotting with a monoclonal antibody reactive with both P450IA1 and P450IA2. In rats, PhIP induced P450IA1, P450IA2 and a new but unspecified P450 isozyme in the liver, and induced P450IA1 in the kidney. However, PhIP induced none of these P450 isozymes in mice, hamsters and guinea pigs. PMID- 1452457 TI - Significance of strain and sex differences in the development of 252Cf neutron induced liver tumors in mice. AB - Mouse liver tumors occurring in C3H/HeN, C57BL/6N and C3B6F1 hybrid (C3H x C57BL) were studied following 252Cf fission neutron irradiation. Three strains of mice of both sexes (about 30 mice/group) were irradiated once with 252Cf at doses of 0, 12.5, 50 and 200 cGy. The groups were observed for 13 months after irradiation. The incidence of liver tumors in the non-irradiated controls was 0% in both sexes of C57BL/6N, 11.7% in males and 0% in females of C3B6F1 and 39.5% in males and 11.4% in females of C3H/HeN mice. In the four strains of mice thus far studied, including B6C3F1 hybrid (C57BL x C3H) which was previously studied, 252Cf irradiation has increased the tumor incidence dose-dependently in males and in females, but less effectively in females. The mean number and size of liver tumors were clearly correlated with tumor incidence. The incidence was always highest in C3H/HeN mice of both sexes, followed by B6C3F1, C3B6F1 and C57BL/6N mice. The influence of sex hormones was studied in B6C3F1 mice of both sexes after 200 cGy of 252Cf irradiation. In males, the incidence of liver tumors was significantly decreased from 55.2% to 23.3% and 25.9% after orchidectomy, and in females it was slightly decreased from 27.6% to 14.8% and 18.8% after ovariectomy. Supplementation of testosterone in orchidectomized mice did not restore the occurrence of liver tumors. PMID- 1452458 TI - ras mutations in endocrine tumors: mutation detection by polymerase chain reaction-single strand conformation polymorphism. AB - To elucidate the molecular basis for endocrine tumorigenesis, ras mutations in human endocrine tumors were analyzed using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. Mutations of the H-, K-, N ras genes were examined in genomic DNAs from 169 successfully amplified primary endocrine tumors out of 189 samples. Four out of 24 thyroid follicular adenomas analyzed contained mutated N-ras codon 61, and one contained the mutated H-ras codon 61. One of the 19 pheochromocytomas revealed mutation of the H-ras codon 13. No mutations of the ras gene were detected in pituitary adenomas, parathyroid tumors, thyroid cancers, endocrine pancreatic tumors, and adrenocortical tumors. Based on these findings we conclude that activation of the ras gene may play a role in the tumorigenesis of a limited number of thyroid follicular adenomas and pheochromocytomas, and that mutation of the ras gene is not frequent in other human endocrine tumors. PMID- 1452459 TI - Altered glycosylation of membrane glycoproteins associated with human mammary carcinoma. AB - N-Linked sugar chains of normal mammary gland, mammary carcinomas (primary lesion), and axillary lymph node metastases of mammary carcinomas were released from their membrane preparations by hydrazinolysis and their structures were analyzed. Fractionation using a Datura stramonium agglutinin (DSA)-Sepharose column revealed that the metastasized carcinomas contain more than twice as much DSA-binding oligosaccharides as the normal gland, and the primary carcinomas contain an intermediate amount. These oligosaccharides were elucidated to have tri- and tetraantennary structures containing the GlcNAc beta 1-->6(GlcNAc beta 1 ->2)Man group with and without N-acetyllactosamine repeating units. Lectin blot analysis of membrane glycoproteins and histochemical staining of tissues using biotinylated DSA indicated that these glycosylation changes predominantly occur in a limited number of glycoproteins with apparent molecular weights of 90, 160, and 210 kilodaltons, and mammary carcinomas are distinguishable from normal gland by their intense intracytoplasmic staining. PMID- 1452460 TI - DT-5461, a new synthetic lipid A analogue, inhibits lung and liver metastasis of tumor in mice. AB - We have investigated the antimetastatic effect of a new synthetic lipid A analogue, of low endotoxicity, DT-5461, against two highly metastatic tumor cell lines, L5178Y-ML25 T-lymphoma and B16-BL6 melanoma cells in mice. Four intermittent i.v. administrations of DT-5461 at intervals of 4 days resulted in a significant inhibition of liver metastasis caused by i.v. injection of L5178Y ML25 cells and lung metastasis of B16-BL6 cells in the experimental metastasis models. Intraperitoneal and intranasal administrations as well as i.v. administration of DT-5461 were also effective in preventing lung metastasis of the melanoma cells. Multiple administrations of DT-5461 before the surgical excision of primary tumors significantly reduced the number of lung colonies of melanoma cells and primary tumor size. Similarly, this treatment modality after the surgical excision of primary tumors showed a greater reduction of lung tumor colonies as compared with lipopolysaccharide, a synthetic lipid A (No. 506) and its analogue as well as untreated control in the spontaneous lung metastasis model. Furthermore, the group that received DT-5461 after the inoculation of lymphoma or melanoma cells showed significantly enhanced survival rate compared with the untreated control. These results suggested that DT-5461 may be therapeutically useful for the inhibition of tumor metastasis. PMID- 1452461 TI - Inhibition by fibrin coagulation of lung cancer cell destruction by human interleukin-2-activated killer cells. AB - We examined the effect of fibrin coagulation on tumor cytotoxicity mediated by human lymphokine (IL-2)-activated killer (LAK) cells. LAK cells were induced from peripheral blood mononuclear cells (MNC) by culture with recombinant IL-2 for 4 or 5 days, and LAK cell-mediated cytotoxicity against tumor cells was assessed by 51Cr release assay in the presence or absence of plasma from normal subjects and lung cancer patients. Plasma did not affect the phase of induction of LAK activity by IL-2, but dose-dependently inhibited the effector phase of LAK cell mediated cytotoxicity against Daudi cells. Similar inhibition of LAK cell mediated cytotoxicity was observed on pretreatment of Daudi cells and human lung cancer cell lines with human fibrinogen plus thrombin. A parallel relationship was found between the amount of fibrinogen in plasma of lung cancer patients and inhibition of LAK cytotoxicity. This inhibition was reduced by addition of anticoagulants (heparin or argatroban). These findings suggest that fibrin coagulation on tumor cells protects them from LAK cell-mediated tumor cytotoxicity in malignant lesions and that a combination of an anticoagulant drug and IL-2/LAK therapy may be effective for treatment of lung cancer patients. PMID- 1452462 TI - Fluorouracil catabolism in the combination treatment of cyclophosphamide, methotrexate and fluorouracil. AB - The CMF-regimen is amongst the most effective chemotherapeutic approaches in the treatment of breast cancer. It is generally accepted that the efficacy of the combination of the three agents used in the regimen, i.e., cyclophosphamide (CY), methotrexate (MTX) and fluorouracil (FUra), is based on interactions between the drugs at the intratumoral level. In WAG/Rij rats we previously demonstrated that change of FUra clearance at the first day of the CMF-regimen occurs owing to concomitant CY + MTX. In the present study clearance of FUra and the first product of FUra catabolism, FUraH2, were monitored at day 1 and day 8 of the regimen upon treatment with single agent FUra (F), MTX + FUra (MF), CY + FUra (CF), and CY + MTX + FUra (CMF). At the first day of treatment, FUra and FUraH2 systemic exposure was demonstrated to be increased in CMF-treated rats owing to concomitant CY+MTX. At the eighth day of treatment it was found that repeated CY administration during the previous seven days in CF-treated rats resulted in increased FUra and FUraH2 systemic exposure and therefore increased the dose of FUra artificially. It is concluded that altered FUra clearance owing to extratumoral interactions by concomitant CY and MTX contributes to the efficacy of the CMF-regimen. PMID- 1452463 TI - The orbital glands of the chelonians Pseudemys scripta and Testudo graeca: comparative histological, histochemical and ultrastructural investigations. AB - The orbital glands of the chelonians Pseudemys scripta and Testudo graeca were investigated at the histological, histochemical and ultrastructural levels. Four acinar cell types were seen in the harderian gland of P. scripta on the basis of histochemical reactions and ultrastructure. Secretory granules were of 2 types, one showing moderate electron density with an electronlucent core, the other being smaller and more osmiophilic with an electron-dense core. In the harderian gland of T. graeca only 2 glandular cell types were found; one type contained secretory granules with a dense core surrounded by a wide zone of lower density. Acinar cells of the anterior lacrimal gland in both species were of 2 types, one being of mucous type. In the harderian gland and in the lacrimal gland of both species, one cell type appeared not to be involved in the secretion of organic material. These cells contained numerous tightly packed mitochondria among which were abundant clumps of glycogen; the cell membrane was specialised at both edges. This cell type was similar ultrastructurally to the 'salt cells' described in the salt-secreting glands of various marine vertebrates, i.e. of the cells involved in transport processes. These combined histological, histochemical and ultrastructural studies have allowed us to distinguish orbital glands. In the past, the harderian and lacrimal glands in chelonians have often been mistaken for one another. PMID- 1452464 TI - The cutaneous branches of the superior gluteal nerve with special reference to the nerve to tensor fascia lata. AB - Cutaneous branches from the superior gluteal nerve were studied in 39 half pelves (18 right, 21 left) of 23 adult Japanese cadavers. A detailed description of the branches is not currently available in the literature. Most of these branches perforated tensor fascia lata and were distributed to the centre of the lateral gluteal region. PMID- 1452465 TI - Characterisation of ramified microglial cells: detailed morphology, morphological plasticity and proliferative capability. AB - Several cellular properties of brain microglia in the rat were investigated using both whole tissue and cultures of dissociated cerebral cortical cells. As revealed by thiamine pyrophosphatase histochemistry, tissue microglia possessed a highly distinctive cellular morphology. Stained microglia showed similar overall features of morphology and distribution in both preparations; however, the cells in culture displayed some slight differences from those of the tissue, including larger somata and less developed processes. Through studying living ramified cells in culture, both morphological plasticity as evidenced by patterned variations in soma size and mitotic activity were directly confirmed. It was concluded that ramified microglia definitely possess proliferative capability, and this may reduce the need for blood cell recruitment in brain immune responses. In addition, cultured microglia exist in a somewhat more activated state than those in normal tissue, and in some instances undergo further activation as macrophages. This cortical tissue culture system should provide an amenable preparation for investigating the regulation of microglial function. PMID- 1452466 TI - The foramen meningo-orbitale and its relationship to the development of the ophthalmic artery. AB - The incidence of the foramen meningo-orbitale is reported from a sample of 50 adult dried skulls. The foramen meningo-orbitale is not an inconsistent finding, being identifiable in half of the samples studied. Multiple foramina may exist. Although the location of the foramen meningo-orbitale is not fixed, it lies along or near the suture leading superolaterally from the superior orbital fissure. The foramen represents the remnant of an embryonic conduit for the supraorbital division of the stapedial artery en route to the orbit and the developing ophthalmic artery. An alternative, more medial, pathway exists through the superior orbital fissure. The embryonic anastomosis that occurs between the internal and external carotid systems does not occur at the level of this foramen, but closer to the optic nerve as a portion of the primitive 'ring' artery. The term 'stapedial-ophthalmo-lacrimal' foramen is proposed to proclaim the embryonic significance of this foramen. PMID- 1452467 TI - The hamster harderian gland: a combined scanning and transmission electron microscopic investigation. AB - Scanning electron microscopy of the epithelial cells of the female hamster harderian gland reveals a range of surface features. Some cells exhibit a uniform covering of microvilli while others, often with swollen apices, are relatively devoid of microvilli. Surface pitting is frequent for all cells; pits represent regions of exocytotic lipid vacuole release. A similar range of surface appearances occurs in the male gland but here cells with uniform microvilli represent type I cells (characterised by small lipid vacuoles) while swollen cells with sparse microvilli are type II cells (characterised by large lipid vacuoles). It is suggested that different cell forms represent a single cell type in varying activity states. Luminal debris is often marked, consisting chiefly of lipids. Solid porphyrin accretions, sometimes surrounded by neutrophils, are numerous in female (but not male) glands. Interstitial mast cells are also numerous in the female gland. The gland contains fenestrated capillaries and extensive lymphatics. The duct of the gland, which has received little attention, possesses ciliated cells, nonciliated cells and basal cells. Ciliated cells possess kinocilia and relatively tall thin microvilli, as well as some lipid vacuoles. Nonciliated cells bear shorter microvilli, apically located mucoid granules, and lamellar formations of smooth endoplasmic reticulum. The basal cells are squat and pyramidal; their lateral walls, which interdigitate with the main duct cell types, show pronounced folding. PMID- 1452468 TI - Human intervertebral disc acid glycosaminoglycans. AB - Alcian blue critical electrolyte concentration (CEC) staining of intervertebral discs (annulus and nucleus of cervical, thoracic and lumbar discs) distinguished 3 groups where CEC staining correlated with age (less than 3 months; from 3 months to 5 years; over 10 years). The CEC increased markedly (implying increased sulphation of the glycosaminoglycans) in the period of maturation (fetal life to 10 years) and then remained constant throughout adult life. This is at variance with accepted views which attribute such changes to degenerative changes in old age. The major part of the CEC increase occurred after the disappearance of blood vessels from the disc, which is almost complete by 4 years. Our results are compatible with the hypothesis that keratan sulphate replaces chondroitin sulphate, functionally, in conditions of oxygen lack. PMID- 1452469 TI - Delamination of neuroepithelium and nonneural ectoderm and its relation to the convergence step in chick neurulation. AB - We have analysed the characteristics of the neuroectoderm-nonneural ectoderm meeting point at several axial levels in relation to the mechanics of neurulation in each level. The results show wide differences at cephalic and somitic levels. At cephalic levels, where convergence plays an important role, the delamination process appears at the beginning of the convergence step. This phenomenon produces a major isolation of the basal lamina, forming a space between this structure and the epithelial sheet in whose basal surface a new basal lamina begins to form. This cavity contains abundant extracellular matrix stained with ruthenium red (RR) and tannic acid (TA), and its increase in volume correlates with the progressive convergence of neural folds. At somitic levels, where the convergence is not important, delamination involves the progressive formation of a half-moon-shaped cavity. This structure appears between a dorsal attachment point, in the tip of neuroectodermal wall, and a ventral attachment point which coincides with the point of bending that determines the bilateral furrow, if it exists. In this small cavity, delamination is not related to an isolation of basal lamina. The RR-staining of the extracellular matrix in this cavity is scarce and the volume increase is smaller than in the cephalic region. These results are discussed in terms of neural fold convergence and neural tube closure. PMID- 1452470 TI - RT97- and calcitonin gene-related peptide-like immunoreactivity in lumbar intervertebral discs and adjacent tissue from the rat. AB - The innervation of rat intervertebral disc and adjacent ligamentous tissue has been investigated using 2 antibodies, RT97 and anti-calcitonin gene-related peptide. Immunoreactivity to the peptide was found in many fibres throughout the long ligaments around the intervertebral discs and in the periosteum, especially associated with vascular channels entering the vertebral bodies. Few of the immunoreactive fibres entered the annular lamellae of the disc tissue. Most of those which terminated did so as fine fibres which lay close to, or in, the interlamellar spaces of the outer annulus fibrosus. Calcitonin gene-related peptide-like immunoreactivity was also found in more complex endings in the longitudinal ligaments and rarely within the annulus fibrosus. RT97 immunoreactivity was also present in the complex endings and associated fibres. Conversely, RT97-immunoreactivity was apparent only in a few fine filamentous fibre endings. This suggested that the majority of fine filamentous, or free, nerve endings were of an unmyelinated sensory origin. Alternatively, those endings of a more complex nature, which were RT97-immunoreactive, were of a myelinated sensory origin. No immunoreactivity to either antibody was seen in the inner annular or nuclear tissue. It was therefore concluded that the sensory innervation of the rat intervertebral disc has both myelinated and unmyelinated components, the latter being more extensive. Both types of innervation appear to be restricted to the outermost rings of the annulus fibrosus. PMID- 1452471 TI - Morphometry of cupromeronic blue-stained proteoglycan molecules in animal corneas, versus that of purified proteoglycans stained in vitro, implies that tertiary structures contribute to corneal ultrastructure. AB - Isolated, purified small chondroitin (dermatan) sulphate proteoglycans from corneas of cow and rabbit and cow sclera were stained with Cupromeronic blue in 'model' experiments. The lengths and thicknesses of the images were compared with those of the same proteoglycans stained in the tissue, using the critical electrolyte concentration principle to give specificity for sulphated proteoglycans, and keratanase 1 or chondroitinase ABC digestion to distinguish between chondroitin and keratan sulphate. Corrections for orientation of the stained glycan filaments within the section plane were made to convert the observed lengths to true average lengths. Observed lengths of stained chondroitin (dermatan) sulphate were greater than those of keratan sulphate, both in models and tissues, in agreement with published data from biochemical and rotary shadowing studies, in both species. Corrected (true) average lengths of stained isolated chondroitin (dermatan) sulphate proteoglycans were slightly, but not significantly, longer than expected from rotary shadowing or biochemical measurements. Keratan sulphate lengths were similarly somewhat longer. The data support the idea that Cupromeronic blue acts as a scaffold that helps maintain polyanion shape against distortion on staining. Stained filaments in tissues were sometimes over twice the length of isolated stained proteoglycans, suggesting that 2 glycan chains were aligned end-to-end. Thicknesses of proteoglycan filaments suggested that at least 2 glycan chains were aligned side-by-side, both in models and in tissues. A scheme for proteoglycan tertiary structure in cornea is proposed, in which glycan chains may bridge collagen fibrils in duplexed forms similar to those observed in rotary shadowed preparations. PMID- 1452472 TI - Parvalbumin and calbindin immunoreactivity in the cerebral cortex of the hedgehog (Erinaceus europaeus). AB - To investigate the morphology and distribution of nonpyramidal neurons in the brain of insectivores, parvalbumin and calbindin 28 kDa immunoreactivity was examined in the cerebral cortex of the hedgehog (Erinaceus europaeus). Parvalbumin-immunoreactive cells were found in all layers of the isocortex, but in contrast to other mammals, a laminar organisation or specific regional distribution was not seen. Characteristic parvalbumin-immunoreactive neurons were multipolar cells with large ascending and descending dendrites extending throughout several layers. Calbindin-immunoreactive neurons were similar to those found in other species, although appearing in smaller numbers than in the cerebral cortex of more advanced mammals. The morphology and distribution of parvalbumin- and calbindin-immunoreactive cells in the piriform and entorhinal cortices were similar in hedgehogs and rodents. Parvalbumin-immunoreactive cells in the hippocampal complex were pyramidal-like and bitufted neurons, which were mainly found in the stratum oriens and stratum pyramidale of the hippocampus, and in the stratum moleculare and hilus of the fascia dentata. Heavily stained cells were found in the deep part of the stratum granulare. Intense calbindin immunoreactivity occurred mainly in the granule cell and molecular layers of the dentate gyrus and in the mossy fibre layer. The most outstanding feature in the hippocampal complex of the hedgehog was the extension of calbindin immunoreactivity to CA1 field of the hippocampus, suggesting, in agreement with other reports, that mossy fibres can establish synaptic contacts throughout the pyramidal cell layer. PMID- 1452473 TI - Quantitative study of the development and maturation of human oesophageal innervation. AB - By 8 wk gestation, the human fetal oesophagus is identifiable as a hollow epithelium-lined tube with primitive nerve and muscle precursors present. From 8 16 wk gestation, the muscle layers and innervation mature until fetal swallowing commences at 16 wk. This study examines quantitatively the development and maturation of nerve fibres and cell bodies within the oesophagus using histochemistry. Oesophageal samples (n = 35) from 8 wk gestation to 28 months of age and adults (n = 3) were immunostained using antisera for the general nerve marker, protein gene product (PGP 9.5), the glial tissue marker S100, and the synaptic vesicle protein synaptophysin (p38). Histochemical staining for NADH diaphorase enzyme activity was also used to identify neurons. Computer-assisted image analysis of the muscularis externa permitted detailed quantification of cell size, nerve density and myenteric (plexus) fraction. At 8 wk gestation, PGP and synaptophysin were present in immature neurons throughout the cytoplasm, but from 10 wk synaptophysin was localised solely at nerve synapses. S100 immunoreactivity was also detected from 8 wk gestation onwards and was confined to glial tissue. Nerve cell size increased with maturation from 6 microns at 8 wk gestation to 20 microns at term and 21 microns at 28 months. The numbers of cells, nerve density (% area occupied by nerves throughout section) and myenteric fraction (% area occupied by ganglion cells and nerve fibres within the myenteric plexus) all peaked at 16-20 wk gestation and, whereas the number and density then fell towards adult levels, the myenteric fraction fell during the late second trimester and became constant from 30 wk gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452474 TI - High incidence of the median artery of the forearm in a sample of recent southern African cadavers. AB - Observations of the presence of the median artery, providing substantial blood supply to the hand, were conducted on 96 dissected forearms of 15 adult African females and 49 adult males. The artery has a much higher incidence (27.1%) than previously reported by any author. There is no significant difference in its occurrence between sexes, nor between right and left limbs. The artery seems to occur more often bilaterally than unilaterally. The presence of the artery is not related to age. From a theoretical standpoint it is difficult to accept that a structure present in more than 1 in 4 of individuals should be considered an 'anomaly' or a 'variant'. A different approach to description of normal human anatomy is therefore necessary--that of presenting alternative anatomical patterns of equal standing rather than a single 'normal' pattern. PMID- 1452475 TI - A variant of flexor carpi ulnaris causing ulnar nerve compression. AB - Anatomical variations of the muscles and nerves around the wrist are common. Knowledge of such variations is derived from 2 sources: anatomical dissections and clinically reported cases. We present a case of duplication of the tendon of flexor carpi ulnaris with splitting of the ulnar nerve. The ulnar slip of the tendon was inserted into the pisiform bone and the radial slip into the proximal phalanx of the ring finger. The anatomical literature and the clinically reported cases of variations of the flexor carpi ulnaris are reviewed. PMID- 1452476 TI - Structural variations in the jugular foramen of the human skull. AB - The jugular foramen was examined in 300 Anatolian skulls from the 17th and 18th centuries. In 61.6% the foramen was larger on the right and in 26% on the left, with the remainder being of almost equal size. An obvious dome caused by a superior jugular bulb was present bilaterally in 49%, on the right only in 36%, on the left only in 6%; it was absent bilaterally in 10.3%. Complete bony septation occurred in 5.6% on the right and in 4.3% on the left, partial septation was observed in 2.6% on the right and in 19.6% on the left. Another foramen which is completely separated by a spicule of bone and which transmits the inferior petrosal sinus was present in 5.6% of skulls on the right and in 4.6% on the left. PMID- 1452477 TI - Interference with interparietal growth in the human skull by the tectum synoticum posterior. AB - The tectum synoticum posterior, which is one of the 3 skull roof elements of the chondrocranium, interferes with the growth of the human interparietal bone, thus giving rise to lateral incisures in the bone. Our observations on the developmental fate of the incisures strongly suggest that the sutura mendosa is the remnant of these incisures. PMID- 1452478 TI - A rare anomaly of 5 ossicles in the pre-interparietal part of the squamous occipital bone in north Indians. AB - Examination of 125 adult north Indian skulls revealed a rare anomaly of 5 large ossicles in the upper central part of the squamous occipital bone. Their location and possible derivation are briefly discussed. PMID- 1452479 TI - Undergraduate medical anatomy teaching. PMID- 1452480 TI - Intracellular axonemes within ciliated cells in the tracheal epithelium of domestic pigs. AB - Extended aggregates of intracellular axonemal derivatives can be seen within the apical cytoplasm of ciliated cells of apparently healthy domestic pigs. Such alterations were observed in 15 out of 20 animals. Complete (9 + 2) or incomplete (8 + 2 - 5 + 2) intracellular axonemes were found which sometimes arose from mature, irregularly arranged kinetosomes. In addition, bundles of single microtubules and microtubular pairs were found. In previous investigations on the ciliated epithelium of different mammals, intracellular axonemes were investigated only under pathological or experimental conditions. Our findings indicate that these alterations also occur in healthy animals. The extended aggregates of intracellular axonemal derivatives are more likely to be due to a failure of ciliary maturation than to a degradation of incorporated mature cilia. PMID- 1452481 TI - Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus. AB - A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connectivity. From a descriptive standpoint, 3 neuronal types were found with respect to the number of dendritic stems arising from the neuronal soma: bipolar neurons (48%), multipolar neurons (45.5%) and monopolar neurons (6.5%). Within the multipolar type 2 subtypes could be distinguished, taking into account the number of dendritic spines: (a) with few spines (93%) and (b) very spiny (7%). These results indicate that the hedgehog SON is similar to that in other species except for the very spiny neurons, the significance of which is discussed. In order to characterise the main types more satisfactorily (bipolar and multipolars with few spines) we undertook a quantitative Golgi study of their dendritic fields. Although the patterns of the dendritic field are similar in both neuronal types, the differences in the location of their connectivity can reflect functional changes and alterations in relation to the synaptic afferences. PMID- 1452482 TI - The effects of clenbuterol on satellite cell activation and the regeneration of skeletal muscle: an autoradiographic and morphometric study of whole muscle transplants in mice. AB - The beta-2 agonist clenbuterol was tested for its effect on the proliferation of satellite cells in transplanted skeletal muscles. Using autoradiographic techniques it was found that satellite cells in clenbuterol treated transplants began proliferating earlier than in control animals. The effect of clenbuterol on the growth of regenerating muscle fibres was also examined using morphometric techniques, which manifested itself as hypertrophy of the fibres when compared with the controls. PMID- 1452483 TI - The effects of pre- and posttransplantation exercise on satellite cell activation and the regeneration of skeletal muscle transplants: a morphometric and autoradiographic study in mice. AB - The effects of pre- and posttransplantation exercise on satellite cell activation, and the eventual regeneration of skeletal muscle transplants, were studied histologically, morphometrically and autoradiographically. It was found that satellite cells in these transplants were synthesising DNA 30 h after transplantation, and the transplants appeared to be revascularising at 60 h after surgery. Respectively, this was 18 and 12 h earlier than found in previous studies on nonexercising muscle using the same techniques. The morphometric analysis showed hypertrophy of the muscle fibres of the exercised transplants when compared with controls, and also an increase in the capillarity of the exercised transplants. PMID- 1452484 TI - Anatomical aspects of the lacrimal gland of the tufted capuchin (Cebus apella). AB - In the tufted capuchin (Cebus apella) the main lacrimal gland is composed of 2 distinct portions with an intraorbital and extraorbital localisation, interconnected by a bridge of glandular tissue which crosses the lateral orbital wall through the lateral orbital fissure located in the sphenozygomatic suture. The intraorbital lacrimal gland is flattened and extremely thin, with a variable outline. It lies on the upper and outer third of the globe of the eye, and the aponeurosis and the belly of the lateral rectus muscle, extending antero posteriorly from the upper lateral angle of the orbit midway along the orbital cavity. The extraorbital lacrimal gland is compact, halfmoon-shaped, with 3 surfaces, 3 borders and 2 extremities. It lies in the temporal fossa between the temporalis muscle and the temporal surface of the zygomatic bone, fitting into a depression in this bone, and totally surrounded by adipose tissue. The secretory cells have a flocculent appearance and either low or high density. They possess a basal region containing the nucleus and rich in granular endoplasmic reticulum, and an apical region filled with secretory granules varying in size, form and density. PMID- 1452485 TI - Characterisation of secondary spermatocytes in the marbled newt (Triturus marmoratus). AB - Secondary spermatocytes in the marbled newt (Triturus marmoratus) were identified by means of cytophotometric quantification of nuclear DNA in the testicular lobules containing primary spermatocytes in advanced stages of the first meiotic division (from pachytene onwards) and newly formed spermatids. The nucleus of secondary spermatocytes has an intermediate size between that of primary spermatocytes and round spermatids and was characterised by the presence of abundant masses of dense chromatin and the absence of a nucleolus. At the prophase the chromatin masses were located at the periphery of the nucleus. The ultrastructural study revealed that the nuclear envelope displayed blebs and that the cytoplasm was very similar to that of primary spermatocytes including the presence of smooth endoplasmic reticulum whorls, multiple small dictyosomes, and a proacrosomal-like granule near the nucleus. This granule stained weakly with aqueous PTA and was observed in about 6% of secondary spermatocytes. Many of the mitochondria were grouped beneath the plasma membrane. Approximately 2% of these cells presented an axoneme which was not associated with other flagellar components. PMID- 1452486 TI - Microvessel and astroglial cell densities in the mouse hippocampus. AB - In order to study the factors responsible for glucose uptake in the mouse hippocampus, microvessel and astroglial cell densities were measured and compared in each laminal region. Microvessel density was examined on histologically prepared sections after injection of Indian ink and measured by means of an image analyser. Astroglial cell density was determined after the cells were stained immunohistochemically. Microvessel and astroglial cell densities were determined in 10 different hippocampal structures. Microvessel and astroglial cell densities were strongly correlated in all layers except the pyramidal cell layers. The highest density of perfused microvessels was found in the stratum lacunosum moleculare, compared with other regions, and the lowest values were found in the stratum lucidum and dentate granular cell layer. Among pyramidal cell layers, microvessel density in sector CA3a was significantly higher than that in CA1. PMID- 1452487 TI - The ampulla of the ductus deferens in man: morphological and ultrastructural aspects. AB - In order to compare the histology of the ampulla of the ductus deferens with that of the other segments of the duct in man, the seminal vesicle and the adjacent 13 15 cm of the ductus deferens were obtained during cystectomy from 15 adult men, and were processed for light and electron microscopy. Each ductus deferens specimen was divided into 3 segments: segment A or initial segment (the most proximal to the testis) showing a smooth outer surface and, on section, a uniform lumen and absence of mucosal invaginations; segment B (1.5-4 cm) showing a smooth outer surface and, on section, small cavities in the mucosa; and segment C or ampulla (3-4 cm), which was easily recognisable because of the cerebriform pattern on its outer surface. Segment A showed the usual histological pattern reported in studies of the human ductus deferens. Segment B consisted of mucosa, muscularis mucosae, submucosa, muscular coat and adventitia. The epithelial lining formed multiple branched invaginations in the lamina propria and submucosa giving rise to glandular structures. The lumen of the duct and the glands were lined by the same cell types: (1) basal cells; (2) mitochondrion-rich cells; and (3) columnar cells with the ultrastructural features of glycoprotein-secreting cells. The latter cells could be classified into 3 subtypes suggesting different stages of development: (a) with abundant mitochondria; (b) with abundant rough endoplasmic reticulum; and (c) with abundant secretory granules. Segment C or the ampulla showed the same histology as segment B except for the presence of many diverticula in the ampulla.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452488 TI - Rethinking options for the treatment of shigellosis. PMID- 1452489 TI - The site concentrations of antimicrobial agents in the lung. PMID- 1452490 TI - Antibacterial profile of flurithromycin, a new macrolide. AB - The in-vitro activity of flurithromycin against common respiratory tract Gram positive (85 strains) and Gram-negative (44 strains) pathogens, and a collection of anaerobes (125 strains) was compared with that of erythromycin, cefixime, amoxycillin, co-amoxiclav, ciprofloxacin, netilmicin and clindamycin. Flurithromycin possessed the same spectrum and potency of antimicrobial activity as erythromycin. The presence of 50% human serum in the test media enhanced the activity of flurithromycin against all isolates, with the exception of Streptococcus pyogenes. Flurithromycin induced a post-antibiotic effect (PAE) that ranged from 0.25 h (Haemophilus influenzae) to 3.5 h (Streptococcus pneumoniae) for all strains tested. The presence of serum increased or diminished the duration of the PAE, depending on the strain being analysed. No interaction between flurithromycin and the other drugs tested was observed by the checkerboard technique, but when the time-kill system was used, 35 cases of synergy were noted out of 120 tests performed (29%), of which 15 (43%) were with Moraxella catarrhalis, 12 (34%) with Staphylococcus aureus, four (11%) with H. influenzae and the remainder with S. pneumoniae and S. pyogenes. Netilmicin produced most synergic interactions. Antagonism was not detected by either methods. PMID- 1452491 TI - The combined effect of iron chelators and classical antimalarials on the in-vitro growth of Plasmodium falciparum. AB - The emergence of drug resistant malaria has prompted an intensified search for new antimalarials or combinations of such drugs. Iron chelating agents may represent a new approach to antimalarial treatment and could possibly be used in combination with classical antimalarials. Plasmodium falciparum (FCR-3) strain used at a 1% haematocrit, was subjected to various combinations of the classic antimalarials (chloroquine, pyrimethamine and quinine) and iron chelating agents (desferrioxamine and 2,2'-bipyridyl) in vitro. Tritiated hypoxanthine incorporation was used to determine the growth of the malarial parasites. The iron chelating agents and classic antimalarials when tested alone were found to inhibit the growth of the late stages of the parasite. The combination of the classic antimalarials and iron chelating agents resulted in additive effects on the in-vitro growth of P. falciparum. PMID- 1452492 TI - Decreased susceptibility of penicillin-resistant pneumococci to twenty-four beta lactam antibiotics. AB - The in-vitro activity of 24 beta-lactam antibiotics was compared using three groups of pneumococci and an agar dilution method comprising 100 penicillin susceptible, 100 intermediately penicillin-resistant, and 100 highly penicillin resistant pneumococcal strains. Our results show that intermediately penicillin resistant and highly penicillin-resistant pneumococci had decreased sensitivity to other beta-lactam agents. According to their relative in-vitro activity, the antimicrobials were classified into three groups. The first group included drugs more active than penicillin (imipenem, meropenem, cefotaxime, ceftriaxone, and cefpirome), which could be useful for the treatment of infections due to penicillin-resistant strains. The second group showed slightly lesser activity than did penicillin, and included: ampicillin, cefdinir, cefuroxime, cefoperazone, azlocillin, mezlocillin, piperacillin, cephalothin, and cefamandole. The remaining antibiotics (oxacillin, cefixime, ceftizoxime, cefetamet, cefaclor, ceftazidime, cefoxitin, cefonicid, and latamoxef) showed poor activity against penicillin-resistant strains, precluding their use for empirical treatment in areas with a high prevalence of penicillin-resistant strains. PMID- 1452493 TI - Rapid increase in the prevalence of high-level aminoglycoside resistance among enterococci isolated from blood cultures during 1989-1991. AB - At St Elizabeth Hospital Medical Center in Youngstown, Ohio, USA, the first blood culture isolate of Enterococcus faecalis with high-level gentamicin resistance (MIC > 2000 mg/L) was seen in 1985, and the prevalence of high-level gentamicin resistance among enterococci isolated from blood cultures during 1985-8 was 9%. During the period 1989-91, the prevalence of high-level gentamicin resistance among enterococci isolated from blood cultures increased to 35% (44 of 126 strains). Increases in the prevalence of high-level resistance to amikacin, tobramycin, netilmicin, kanamycin and streptomycin were also demonstrated. Ten of 44 strains (23%) with high-level gentamicin resistance did not exhibit high-level resistance to streptomycin. Of the 126 strains of enterococci, 52% had high-level resistance to at least one aminoglycoside. PMID- 1452494 TI - Antibiotic sensitivity of ribosomes from wild-type and clindamycin resistant Bacteroides vulgatus strains. AB - The sensitivity to different antibiotics of in-vitro polyuridylic acid-dependent polypeptide synthesizing system from Bacteroides vulgatus RYC18F6 and two clindamycin-resistant derivatives was studied. The ribosomes from the resistant strains were not affected by concentrations of up to 0.1 mM clindamycin and lincomycin. In contrast, streptogramin B was found to cause strong stimulation of the clindamycin-resistant polymerizing systems. The modified ribosomes from the resistant strains were more sensitive to other antibiotics like sparsomycin and chloramphenicol. The data indicate that resistance in these B. vulgatus mutant strains is due to alteration of the ribosome structure. PMID- 1452495 TI - Inhibition of Chlamydia trachomatis growth in mouse fibroblasts by liposome encapsulated tetracycline. AB - The in-vitro susceptibility of Chlamydia trachomatis to liposome-encapsulated tetracycline was determined and compared with free tetracycline. Anionic, cationic and neutral small unilamellar liposomes were used in this study. Chlamydia-infected mouse fibroblast monolayers were continuously exposed to varying concentrations of antibiotic, incubated for 48 h and Giemsa stained. The minimum inhibitory concentration (MIC) for anionic, cationic and neutral liposomes containing tetracycline were 0.38, 0.08 and 0.04 mg/L, respectively. This was approximately 2, 10, and 20 times more efficient than free tetracycline (MIC, 0.79 mg/L). Neutral liposomes displayed no visible toxic side-effects on the host cells. When compared with free tetracycline, neutral liposomes were the most efficient for the delivery of inhibitory concentrations of tetracycline to chlamydia-infected mouse fibroblast L cell cultures. PMID- 1452496 TI - In-vitro effects of liposome-encapsulated amphotericin B (AmBisome) and amphotericin B-deoxycholate (Fungizone) on the phagocytic and candidacidal function of human polymorphonuclear leucocytes. AB - Liposomal amphotericin B (AmBisome), at concentrations > or = 20 mg/L, and amphotericin B-deoxycholate (DC) (Fungizone), at concentrations > or = 1 mg/L, both caused a significant reduction in neutrophil uptake of Candida albicans blastospores following simultaneous addition of the drug with the blastospores. The reduction in uptake was seen also in tests in which blastospores were pre treated with the drugs for 60 min, but was not detected in tests in which neutrophils were pre-treated for 60 min. Neither formulation affected neutrophil killing of C. albicans blastospores following simultaneous addition of the drug with the blastospores. However, previous treatment of the neutrophils with either formulation at a concentration of 20 mg/L led to enhanced killing of ingested blastospores. The results suggest that much higher concentrations of liposomal amphotericin B (AmBisome) are required to produce deleterious effects on neutrophil phagocytic function than with the conventional formulation of the drug. PMID- 1452497 TI - Comparative activity of glycopeptide antibiotics against coagulase-negative staphylococci embedded in fibrin clots. AB - The susceptibilities of 16 strains of coagulase-negative staphylococci to vancomycin and teicoplanin were determined by three microdilution methods run in parallel; (i) a reference method in which the medium was Iso-Sensitest broth, (ii) a method in which the organisms were suspended in plasma and (iii) one in which the bacteria were incorporated into a fibrin clot. In comparison with the reference method there was a less than two-fold change in the geometric mean MICs of both antibiotics in plasma, while in clot the increase was 12-fold for vancomycin and 28-fold for teicoplanin. MBCs showed a similar trend although the increase was greater for teicoplanin. These results suggest that protein binding may have a much greater impact on antimicrobial activity when the mobility of the protein is reduced within a clot. PMID- 1452498 TI - In-vitro and in-vivo evaluation of the antistaphylococcal activity of S-5556, a new 16-membered macrolide. AB - During recent years, a resurgence of interest in the macrolides had led to the discovery of new derivatives of erythromycin with improved antibacterial activity and pharmacokinetic properties. In this study the in-vitro and in-vivo antistaphylococcal activity of S-5556, a 16-membered macrolide, was evaluated. In vitro, S-5556 was slightly less active than erythromycin against methicillin susceptible Staphylococcus aureus. In contrast, it had superior activity for methicillin-resistant S. aureus (MRSA); several of these strains with inducible resistance to the macrolides-lincosamides-streptogramins group were susceptible to S-5556 whereas erythromycin was inactive. The combination of S-5556 with oxacillin was synergic for most MRSA strains tested. In vivo, a single prophylactic dose of S-5556 prevented 75%-100% of the cases of acute staphylococcal subcutaneous foreign body infection in a guinea pig-model. In a rat-model of chronic implant infection due to a methicillin- and erythromycin resistant S. aureus strain, S-5556 significantly decreased the bacterial concentration around the foreign material, however resistant mutants emerged. PMID- 1452499 TI - The anti-inflammatory effect of erythromycin in zymosan-induced peritonitis of mice. AB - The anti-inflammatory effect of erythromycin was investigated using zymosan induced peritonitis in mice. When mice were given erythromycin 10 mg/kg/day po for 28 days, a marked suppression of inflammatory responses, including the reduced influx of leucocytes, plasma exudation and prostaglandin E2 synthesis, was observed. However, neither a 7-day treatment with erythromycin nor a 28-day treatment with clindamycin suppressed the response. The anti-inflammatory activity induced after a 28-day treatment with erythromycin was comparable to the anti-inflammatory effect conferred by a 2-day treatment with dexamethasone 40 microgram/mouse/day. Thus, these data confirm previous studies which show that erythromycin can exert an anti-inflammatory effect when used over long periods of time. PMID- 1452500 TI - Amoxycillin-resistant oral streptococci and experimental infective endocarditis in the rabbit. AB - The ability of three amoxycillin-resistant strains of Streptococcus sanguis 254, 24 and 297 (MIC 40 mg/L) to cause infective endocarditis (IE) in the rabbit was investigated. These strains all produced infection in the rabbit, as did an antibiotic sensitive control strain NCTC 7864. Prophylactic amoxycillin (400 mg/kg body weight) administered one hour before bacterial challenge prevented 80% of the animals developing IE irrespective of the challenging strain. It is concluded that amoxycillin-resistant strains of S. sanguis can cause IE and that amoxycillin prophylaxis can still be effective against these bacteria. PMID- 1452501 TI - Efficacies of amphotericin B lipid complex (ABLC) and conventional amphotericin B against murine coccidioidomycosis. AB - The comparative activities of two preparations of amphotericin B against Coccidioides immitis were investigated. These preparations were a deoxycholate suspension (conventional amphotericin B) and a lipid-based formulation, amphotericin B lipid complex (ABLC). In-vitro susceptibility testing demonstrated that the MICs of ABLC were < or = 0.25 mg/L and of conventional amphotericin B were 0.5 mg/L for C. immitis. However, conventional amphotericin B was at least four-fold more fungicidal, with a minimum fungicidal concentration of 4.0 vs > 16 mg/L for ABLC. The therapeutic efficacies were tested in murine models of acute systemic coccidioidomycosis. Female CD-1 mice were infected iv with C. immitis arthroconidia to establish high (> 50%) or low (< 50%) mortality models. Therapy with conventional amphotericin B or ABLC was given three times per week for two weeks starting three days post-infection. Controls received no therapy or drug free diluent only. Survival was tallied up to 49 days post-infection and the fungal cfu counts in spleen, liver, and lungs of all survivors were determined. In the low mortality study all treated mice survived and all therapy regimens reduced infection in all organs. All mice given ABLC 6.6 or 13.2 mg/kg/dose and 80% given ABLC 16.5 mg/kg/dose, as well as 90% given conventional amphotericin B 0.66 mg/kg/dose were free of infection; all controls remained infected. In two high mortality studies, all mice given ABLC 0.66-20 mg/kg/dose or conventional amphotericin B 0.22 or 0.66 mg/kg/dose survived compared with 0-20% of controls. Thirty per cent of uninfected mice given ABLC 20 mg/kg/dose and 40% given conventional amphotericin B 2.0 mg/kg/dose died due to drug toxicity. Mice given ABLC or conventional amphotericin B had lower residual cfu counts of C. immitis in all organs than did controls. Sixty to one hundred per cent of mice given ABLC regimens > or = 6.6 mg/kg/dose were cured, whereas all controls and 50-60% of mice receiving the highest non-toxic conventional amphotericin B regimen (0.66 mg/kg/dose) remained infected. At equal non-toxic amphotericin B doses, conventional amphotericin B was more effective than ABLC in reducing cfu in infected organs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1452502 TI - Multiple dose pharmacokinetics, safety, and effects on faecal microflora, of cefepime in healthy volunteers. AB - In a randomized, double-blind, placebo-controlled study in 12 healthy volunteers pharmacokinetics, safety and impact on the faecal microflora of cefepime were determined. For eight days eight volunteers received cefepime 1000 mg bd by constant infusion over 30 min, four volunteers received placebo. Concentrations of cefepime in serum and urine were measured by bioassay and HPLC. The correlation between the two methods was good and the bioassay results were used for pharmacokinetic calculations. The faecal flora was analysed twice before the study, twice during the study and four times after cefepime administration. There were no significant differences in the pharmacokinetic parameters between days 1 and 8. The following values (mean +/- S.D.) represent day 1. The maximum concentration of 72.69 +/- 12.2 mg/L immediately after infusion decreased to 0.56 +/- 0.17 mg/L after 12 h. The mean 12 h recovery in urine was 93.69 +/- 2.14%. Pharmacokinetic parameters based on an open two-compartment model were as follows (mean +/- S.D.): area under the curve, 142.65 +/- 18.35 mg.h/L; elimination half life 110.3 +/- 8.3 min; steady state volume of distribution 16.0 +/- 1.9 L/70 kg; total clearance, 107.0 +/- 16.0 mL/min; renal clearance 103.0 +/- 15.2 mL/min. No accumulation was observed during the eight day study period with cefepime at this dosage; trough levels on days 2-7 ranged from 0.52 +/- 0.26 mg/L to 0.90 +/- 0.33 mg/L. In the cefepime treated group the following side-effects were noted: headache (5), fatigue (4), nausea/stomach ache (2), soft stool (2), transient scotoma (1). Side-effects in the placebo group were: headache (2) fatigue (3), nausea/stomach-ache (1), soft stool (2) and photophobia (1). During cefepime administration a decrease in the number of Escherichia coli and bifidobacteria in faeces was observed, whereas Bacteroides spp. and clostridia showed a slight increase. The numbers of faecal bacteria returned to normal 20 to 48 days after the study was completed. PMID- 1452503 TI - Bronchoalveolar distribution of cefuroxime axetil and in-vitro efficacy of observed concentrations against respiratory pathogens. AB - The concentrations of cefuroxime in human alveolar macrophages (AM), epithelial lining fluid (ELF), bronchial mucosal biopsies and serum were measured after a single dose, equivalent to 500 mg of cefuroxime base, given in the form of the orally-administered pro-drug, cefuroxime axetil. Fourteen patients undergoing fibreoptic bronchoscopy with bronchoalveolar lavage were studied. The mean ELF concentration was 0.7 mg/L, that of bronchial biopsies was 1.8 mg/kg and that of serum 3.5 mg/L. AM-associated cefuroxime was detected in nine patients. To assess the in-vitro activity of the concentrations achieved at the potential sites of infection, clinical isolates of common respiratory pathogens were exposed to two concentrations of cefuroxime, based on the observed concentrations in ELF and bronchial mucosa. ELF and mucosal site concentrations were effective against Streptococcus pneumoniae (except one strain with reduced susceptibility to benzyl penicillin) and Haemophilus influenzae. The ELF concentration was less effective against Moraxella catarrhalis. PMID- 1452504 TI - Pharmacokinetics of aztreonam in patients with liver cirrhosis and ascites. AB - The pharmacokinetics of aztreonam were studied in six healthy male subjects (group I) and 12 male patients with post-hepatitis liver cirrhosis and ascites. Patients were allocated into two groups according to serum creatinine; group II included nine patients with serum creatinine. < or = 15 mg/L while group III included three patients with serum creatinine > 15 mg/L. Aztreonam 1 g was given as iv bolus injection. Aztreonam reached a peak concentration in the ascitic fluid (AF) of 6.2 +/- 2.3 mg/L at 4 h, and of 8.7 +/- 4.4 mg/L at 6 h in groups II and III respectively. The level of the drug in AF 24 h post-dosing was still higher than MIC90 for Enterobacteriaceae in most patients. The half-life of elimination from serum increased significantly (P > 0.001) from 1.82 +/- 0.14 h in group I to 6.6 +/- 2.1 h and to 8.87 +/- 0.2 h in groups II and III, respectively. Both the central and the terminal volumes of distribution were higher in cirrhotic patients than in healthy volunteers. Liver cirrhosis and ascites resulted in a significant increase (P < 0.001) of the total body clearance (Cl) of aztreonam from 84 +/- 8 mL/h/kg in group I to 209 +/- 87 mL/h/kg in group II. However, the concomitant association of mild renal impairment in group III abolished this increase; Cl in group III was 122 +/- 50 mL/h/kg. The AUC0-infinity serum was 137.5 +/- 12.2, 78.5 +/- 24.9 and 151 +/- 42 mg.h/L in groups I, II and II, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452505 TI - Stability of ceftriaxone solution. PMID- 1452506 TI - Oral cephalosporins. PMID- 1452507 TI - Detection of beta-lactamase production in Moraxella catarrhalis. PMID- 1452508 TI - Serum monitoring of teicoplanin. PMID- 1452509 TI - Acquired platelet function defects. AB - Platelet dysfunctions, especially acquired forms, are common causes of hemorrhage, especially when associated with trauma or surgery. Although the hereditary platelet function defects are generally quite rare, hereditary storage pool disease is common enough to be suspected in an individual, usually a child, with characteristic historical and clinical findings. The acquired platelet function defects, especially those resulting from drugs, are very common and should promptly be suspected in patients developing easy and spontaneous bruising, mild to moderate mucosal membrane hemorrhage, or unexplained bleeding associated with trauma or surgery. The template bleeding time is generally useful as a screening test of platelet function, but a normal template bleeding time, in the face of a suggestive history, suggestive clinical findings, or in the patient frankly bleeding, is not reliable, and platelet aggregation or lumi-aggregation should be done in appropriate clinical situations. Also, prolongation of the template bleeding time is an unreliable predictor of clinical bleeding propensity. The mainstay of therapy for essentially all these defects, if bleeding is significant, is the liberal infusion of appropriate numbers of platelet concentrates. The acquired platelet function defects should also be managed by attempts to treat or control the underlying disease, if possible, and offending drugs or potentially offending drugs should immediately be stopped. PMID- 1452510 TI - Drug-induced alterations of hemostasis and fibrinolysis. AB - The hemostatic and fibrinolytic systems contribute significantly to the overall pathophysiologic status of a patient in a given clinical setting. Drug modulation of these systems plays a crucial role in the facilitation of the therapeutic effects but may also produce bleeding or thrombotic disorders. Many drugs appear inert; they can, however, modulate both the hemostatic and fibrinolytic systems. Such effects depend on several factors, however, but are significant enough to be recognized for the optimal care of patients. Therefore, it is recommended that the hemostatic and fibrinolytic systems should be routinely monitored during drug delivery. PMID- 1452511 TI - Disseminated intravascular coagulation. AB - Current concepts of the etiology, pathophysiology, clinical and laboratory diagnosis, and management of fulminant and low-grade DIC have been presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding these pathophysiologic interrelationships can the clinician and laboratory scientist appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with DIC. Many therapeutic decisions to be made are controversial and will remain so until more is published about specific therapeutic modalities and survival patterns. Also, therapy must be highly individualized depending on the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis, and hemodynamic and other clinical parameters. Many syndromes that are organ-specific share common pathophysiology with DIC but are typically identified as an independent disease entity, such as hemolytic uremic syndrome, adult shock-lung syndrome, eclampsia, and many other isolated "organ-specific" disorders. PMID- 1452512 TI - Anticardiolipin antibodies and thrombosis. AB - Anticardiolipin antibodies (ACLAs) are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby ACLAs alter hemostasis to induce a hypercoagulable state remain unclear, several theories, as previously discussed, have been advanced. The most common thrombotic events associated with ACLAs are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome), or cerebrovascular/retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). The relative frequency of ACLAs in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through IV) should be defined if possible, because this may dictate both type and duration of both immediate and long-term anticoagulant therapy. PMID- 1452513 TI - Hemostatic abnormalities in multiple myeloma and related disorders. AB - Patients with multiple myeloma, Waldenstrom's macroglobulinemia, benign monoclonal gammopathy, and other B-cell disorders associated with high titer serum paraproteins can manifest unique hemostatic disorders. Most of these disorders predispose the patient to hemorrhage, especially following surgical procedures. Mechanisms can include: acquired von Willebrand syndrome, paraprotein induced platelet function defects, factor X deficiency, and local tissue fragility associated with amyloidosis, abnormalities of the function of fibrin, circulating anticoagulants, and thrombocytopenia. The mainstay of therapy is the treatment of the underlying disease. Depending on clinical circumstances, additional therapies might include: plasmapheresis with appropriate factor replacement, arginine vasopressin, fibrinolysis inhibitors, and splenectomy. Less commonly, the paraprotein disorders are associated with thrombotic complications, especially in those cases in which the lupus anticoagulant is present. PMID- 1452514 TI - Bleeding problems in the cancer patient. AB - Bleeding problems in the cancer patient may result from the effects of the tumor on hemostatic mechanisms or from the treatment of the tumor by cytotoxic and other agents. Among the tumor-related bleeding problems are disseminated intravascular coagulation, primary fibrinolysis, thrombocytopenia, acquired platelet dysfunction, and circulating inhibitors or anticoagulants. Disseminated intravascular coagulation in most solid tumors is associated with hypercoagulability, whereas in acute promyelocytic leukemia bleeding is the most common presentation. Treatment-related bleeding disorders include the common problem of thrombocytopenia secondary to myelosuppressive chemotherapy as well as the interesting microangiopathic hemolytic anemia syndrome associated with mitomycin C and other agents. PMID- 1452515 TI - Diagnosis and treatment of cancer-related thrombosis. AB - Thrombotic events are common causes of morbidity and mortality in patients with neoplastic diseases. Standard diagnostic tests may give misleading results, and the effects of treatment may not be as expected. This article discusses the pathophysiology, diagnosis, and treatment of thrombosis in this difficult setting. PMID- 1452516 TI - Acquired circulating anticoagulants. AB - Acquired inhibitors of blood coagulation, which are pathologic circulating substances that directly inhibit clotting factors or their reactions, most commonly occur in patients with hereditary bleeding disorders. This article contains a discussion of acquired circulating anticoagulants that arise de novo in patients with previously normal hemostatic mechanisms. Pathogenesis and management are also discussed. Treatment of these patients poses a challenge for the hematologist because, unlike hereditary hemophiliacs who have learned to adjust their lifestyle, the acquired hemophiliac is unprepared for hemorrhagic episodes. PMID- 1452517 TI - Cancer cell procoagulants and their implications. AB - Cancer cells induce abnormal blood coagulation through a process that probably involves a combination of increased activators and deficiencies of anticoagulants. The probable participating factors (including tissue factor factor VII and cancer procoagulant) and their role in this process are discussed. The current theory on the role of coagulation in malignant disease is also discussed. PMID- 1452518 TI - Use of blood components in cancer patients with bleeding. AB - The need for blood components for oncology patients is small compared with the need for patients with hematologic malignancies. The subject is important because use of these valuable components is dependent on a limited supply and availability. Agreement on when to use components is extremely important. In fact, at the time of this writing, the Transfusion Practices Committee of the American Association of Blood Banks is conducting an extensive survey on the use of platelets in oncology and hematology cancer patients (Questionnaire on Institutional Policy on Platelet Transfusion Practice for Hematology/Oncology Patients). The results will, we hope, provide a consensus on the proper times and counts that require prophylactic use of components for these patients. Because these patients use the vast majority of components (see Table 15), their proper use is imperative to maintaining an adequate platelet and frozen plasma supply. Transfusion support in cancer patients is vital for their survival. Platelets, in particular, are necessary to prevent serious bleeding. The risks from transfusion must always be considered. Fortunately, with increased monitoring of the blood supply, they have been reduced. As with any therapeutic regimen, these risks must be weighed against the benefit the patient may gain. Transfusion should always be used prudently. PMID- 1452519 TI - Structure and mechanism of action of serpins. AB - Serpins have a central role in regulating proteolysis in blood coagulation, fibrinolysis, and inflammation. Congenital serpin deficiencies cause specific clinical syndromes such as thrombosis with antithrombin III deficiency or emphysema with alpha 1-antitrypsin deficiency. Acquired serpin abnormalities have also been reported, for example, increased PAI-1, which is believed to represent a major risk factor for the development of thromboembolic complications. This article has reviewed the structure/function relationships of serpins and have presented ideas concerning their mechanism of action. The implications of this information for designing drugs that could interfere with serpin function has also been described, and mention has been made of the therapeutic potential of such compounds. PMID- 1452520 TI - Acquired von Willebrand's disease. AB - avWD is a rare entity that is primarily associated with lymphoproliferative disorders, most commonly with multiple myeloma, lymphoma, and the myeloproliferative diseases. Various pathogenetic mechanisms have been postulated. The most commonly seen is antibodies directed against the FVIII complex, resulting in either its accelerated destruction or its accelerated clearance by the reticuloendothelial system. There may be immunoadsorption of the FVIII complexes onto the clones of malignant cells, as has been reported in several cases, or proteolysis may be causing the peripheral destruction of the FVIII complex. Lastly, as seen in hypothyroidism, global decrease in production of the multimers also results in avWD. The treatment, in general, should be aimed at controlling the underlying disorder and at stopping any life-threatening hemorrhage. The treatment includes any or all of the following: DDAVP, cryoprecipitate, FVIII concentrates, extracorporeal immunoadsorption, and chemotherapy as needed to control the underlying disorders. The screening tests that will allow for the detection of the avWD include measurement of the bleeding time, the FVIII:C, FVIII:vWF, and the FVIII:RCoF. FVIII:C inhibitors can be demonstrated by mixing the patient plasma with normal plasma. A normal prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) are expected. Clinically, these patients present with mucosal bleeding, and in avWD tend to have an association with lymphoproliferative malignancies. They tend to be elderly patients with no prior history of bleeding diathesis and to have negative family histories for coagulopathies. Further study of these patients is warranted, because this disorder appears to have a multifactorial etiology. Increasing our understanding of avWD may increase our understanding of congenital vWD, thus allowing us to more effectively treat all patients with von Willebrand's disease. PMID- 1452521 TI - Hypercoagulability and thrombosis. AB - This article has summarized known congenital and acquired alterations of hemostasis leading to thrombosis. Decreases in coagulation inhibitors, including antithrombin III, heparin cofactor II, and protein C and protein S, are of major importance in assessing patients with hypercoagulable states or patients with unexplained thrombosis. Newer assays for components of the fibrinolytic system, plasminogen, t-PA and t-PA inhibitor are also now readily available and are important for defining congenital or acquired fibrinolytic defects leading to hypercoagulability and thrombosis. By judicious use of these assays, combined with clinical evaluation, many patients with thrombosis will have an underlying etiologic blood protein defect defined. Delineating reasons for a thrombotic event is of obvious importance for planning long-term prophylactic therapy and for diagnosing and counseling afflicted family members. In this manner, newly found patients can be treated prophylactically before unalterable morbidity or mortality occurs. PMID- 1452522 TI - Interesting profile emerges amid the clouds of smoke. PMID- 1452523 TI - Radiological case of the month. Osteoblastoma. PMID- 1452524 TI - Glomerular disease in the tropics. PMID- 1452525 TI - Primary isolated hormone deficiencies of hypothalamic pituitary origin. PMID- 1452526 TI - Nervous system cryptococcosis in the immunocompromised. PMID- 1452527 TI - Solitary rectal ulcer syndrome. AB - Solitary rectal ulcer syndrome (SRUS) clinically presents with rectal bleed. Twenty three cases of SRUS are described highlighting that it is a distinct clinicopathological entity which can be diagnosed in the presence of typical clinical features, sigmoidoscopic findings and histopathological appearance of mucosal biopsy. PMID- 1452528 TI - Effect of vasodilator and surface active drugs on the efficacy of peritoneal dialysis. AB - The effect of sodium nitroprusside (SNP), a vasodilator drug, and chlorpromazine (CPZ), a surface active drug, on the efficacy of peritoneal dialysis was studied in 25 patients with acute or acute on chronic renal failure in a double blind fashion. Each drug was added to the dialysate during different sets of cycles. In each patient, six clearance periods of 3 cycles each were studied and peritoneal clearances of creatinine and urea and ultrafiltration rates were measured during each clearance period. SNP increased the peritoneal clearance of creatinine and urea by 28.8 percent each (p < 0.001) while CPZ increased the peritoneal creatinine and urea clearance by 17.7 and 26.0 percent respectively (p < 0.001 each). Both drugs significantly increased the ultrafiltration rates (p < 0.001). SNP was found to be superior to CPZ and had prolonged effect even after cessation of administration. PMID- 1452529 TI - Prevalence of spontaneous bacterial peritonitis. AB - To assess the prevalence of spontaneous bacterial peritonitis (SBP), ascitic fluid cell count, and ascitic fluid culture by conventional method and by bedside inoculation in blood culture bottles were performed in 31 consecutive patients of liver cirrhosis. Seven (22.58%) patients had ascitic fluid polymorphonuclear count (PMN) more than 500/mm. Ascitic fluid culture by conventional method was negative in all the patients, while in 4 patients culture was positive by bedside inoculation method. Six of 7 patients with SBP or its variant were in Child class C. Clinical features in these patients were abdominal pain (5 patients), fever (4) and encephalopathy (2); serum bilirubin level was 6.8 +/- 5.5 mg/dl, serum albumin 1.98 +/- 0.2 g/dl, prothrombin index 59.8 +/- 12.2%, ascitic fluid protein 0.78 +/- 0.24 g/dl. Three of 7 patients with SBP or its variant expired during hospital stay; the other 4 patients recovered after appropriate antibiotic therapy. We conclude that SBP is a serious complication in patients of liver cirrhosis with ascites. Ascitic fluid PMN count and bedside inoculation of blood culture bottles with ascitic fluid are sensitive indicators of SBP. Hence they should be performed routinely for early detection of SBP. PMID- 1452530 TI - Acquired toxic methaemoglobinaemia. AB - Eighty Six adult males presented with central cyanosis and constitutional symptoms 2 to 4 hours following ingestion of meal from a common kitchen. On spectrometry methaemoglobin was detected. All recovered fully in 12 to 36 hours on symptomatic treatment. Epidemiological study and toxicological examination revealed that metanil yellow used for colouring the rice was responsible. PMID- 1452531 TI - Insulin responses to varying hyperglycaemia in newly diagnosed non-insulin dependent diabetic patients. AB - The effect of varying degrees of hyperglycaemia on insulin secretion was studied in newly diagnosed non-insulin dependent diabetic patients, stratified according to the fasting plasma glucose values. Of the 116 patients studied, 62 were non obese and 54 obese. Insulin response patterns during 2h oral glucose tolerance test were analysed in comparison with the values in weight matched control subjects and also with respect to the degree of hyperglycaemia. The effect of hyperglycaemia on beta cell secretion differed in obese and non-obese patients. In the non-obese, fasting insulin levels were within normal range even in those with severe hyperglycaemia while the corresponding values in response to glucose stimulation showed a decreasing pattern. In obese patients, even fasting immunoreactive insulin (IRI) value was decreased and with increasing hyperglycaemia the reduction in IRI response to glucose stimulation was of greater magnitude compared to non-obese patients. Thus the modulating effect of obesity on insulin secretion appears to disappear with development of hyperglycaemia. The insulinogenic index was low in all the diabetic patients. PMID- 1452532 TI - Adverse effects of oral amiodarone therapy. AB - Oral amiodarone was administered to 38 patients (25 males, 13 females) with mean age of 43.6 years. Ventricular and supraventricular arrhythmias were present in 30 and 8 patients respectively. Amiodarone was given as 400-1200 mg/day for 1-2 weeks as loading dose and then it was maintained as 100-600 mg/day. The mean duration of therapy was 12.4 months. Adverse effects were noted in 21 (55.3%) cases. The commonest adverse effects observed were asymptomatic corneal microdeposits followed by gastrointestinal, cardiac, neurological and cutaneous disturbances. The drug was withdrawn in 2 (5.3%) patients because of nausea and vomiting. One patient died of pulmonary infiltrations. It is concluded that adverse effects are common with amiodarone but are tolerated well, making this drug an excellent choice for treatment of cardiac arrhythmias. PMID- 1452533 TI - Experience with bone marrow trephine biopsy. AB - One hundred and ten bone marrow trephine biopsies were studied from January 1987 to July 1989, using Zenker's acetic acid as fixative and routine paraffin embedding. Trephine biopsies were useful in differential diagnosis of cytopenias, especially when bone marrow aspiration was hypocellular or a dry tap, and in staging of lymphomas and multiple myeloma. PMID- 1452534 TI - Entry of drugs into target tissues: antimicrobials. PMID- 1452535 TI - Non A non B hepatitis epidemic in Rewa district of Madhya Pradesh. AB - An epidemic of viral hepatitis occurred at Rewa district of Madhya Pradesh during December 1989 through April 1990. A total of 302 cases were admitted to Gandhi Memorial Hospital. Few cases were reported from the adjacent rural areas. Twenty six of the 40 wards of the city were affected and 7 wards were most affected with attack rates ranging from 3-7 per cent. Seventy one per cent of the hospitalised cases were 15 to 35 years of age. Males constituted 72.2% of the cases. In 37 patients (12.2%) the illness had a fatal outcome. The cases fatality rate was 7.9% in males and 20.6% in females. There were leakages in water supply pipe lines at many places which ran parallel to or were laid across open gutters. The source of infection appeared to be water contaminated by sewage. Results of serological tests indicated a non-A, non-B hepatitis viral aetiology of the epidemic. PMID- 1452536 TI - Functional hypothalamic amenorrhoea-isolated gonadotropin deficiency. AB - A 21 year old female patient with primary amenorrhoea was diagnosed to have isolated gonadotropin deficiency with probable functional hypothalamic amenorrhoea. The evaluation included buccal smear for sex chromatin, trial of medroxy-progesterone acetate, trial of oestrogen-progesterone preparation and estimation of serum prolactin, gonadotrophin and oestrogen levels. When diagnosed as isolated gonadotropin deficiency, treatment with gonadotropin is rewarding. PMID- 1452537 TI - Efficacy of oral fluconazole in Cryptococcus neoformans infection. AB - We report a renal allograft recipient who developed disseminated cryptococcosis, which was treated effectively, with oral fluconazole, a new triazole antifungal agent. The patient is doing well on maintenance therapy with fluconazole and immunosuppressive agents. PMID- 1452538 TI - Hereditary angioedema in a family. AB - Hereditary angioedema is an uncommon clinical condition. Life-long episodic brawny and non-itchy swelling of the extremities, face and trunk, with episodic abdominal pain and familial occurrence are the typical features. Oedema causing obstruction of airways may lead to suffocation and even death. The diagnosis can be confirmed by finding low levels of C1 esterase inhibitor, C4 and C2. Therapy with synthetic androgenic agents can ameliorate the condition to a large extent. PMID- 1452539 TI - Rabies presenting as catatonic stupor. PMID- 1452540 TI - Bilateral cataracts as the presenting manifestation of chronic renal failure. AB - A 26 year old female, a case of chronic renal failure secondary to chronic pyelonephritis with renal osteomalacia, came with dimunition vision as the presenting complaint. She was found to have bilateral cataracts. All other known causes of cataract were excluded. Cataracts due to hypocalcaemia in chronic renal failure are a rare phenomenon. PMID- 1452541 TI - Gelatinous transformation of bone marrow. AB - Gelatinous transformation of bone marrow is usually encountered in patients of anorexia nervosa. We report two cases of gelatinous transformation of the marrow, one without any detectable cause and the other associated with visceral leishmaniasis. PMID- 1452542 TI - Specific chiroglyphic, bronchial asthma and yoga. PMID- 1452543 TI - Chloramphenicol vs ciprofloxacin in enteric fever. PMID- 1452544 TI - Idiopathic oedema. PMID- 1452545 TI - Fibrocalculous pancreatic diabetes in an elderly male. PMID- 1452546 TI - High dose atropine in organophosphorus poisoning. PMID- 1452547 TI - Cholesterol estimation--uniformity suggested at national level. PMID- 1452548 TI - Mitoxantrone for advanced breast cancer. PMID- 1452549 TI - Profile of non-Hodgkin's lymphoma in India. PMID- 1452550 TI - Changing trends in the presentation and treatment of enteric fever: our experience. PMID- 1452552 TI - Chronic myeloid leukaemia with massive lymphadenopathy. PMID- 1452551 TI - Severe hypotension with enalapril. PMID- 1452553 TI - Vegetarians dominate in dermatological disorders. PMID- 1452554 TI - Ciprofloxacin dose in enteric fever. PMID- 1452555 TI - Recognising medical journalism. PMID- 1452556 TI - Total gastrectomy in Zollinger Ellison syndrome: does it have no role today? PMID- 1452557 TI - Combination therapy of parkinsonism with deprenyl. AB - In view of the encouraging results in various trials with deprenyl as an added drug therapy for Parkinson's disease, a pilot study to study deprenyl's efficacy in the Indian population was undertaken. Eleven patients were recruited in this open trial and were objectively assessed by Unified Rating Scale for Parkinsonism of Columbia University, Modified Hoehn and Yahr Staging and Schwab and England activities of daily living. Side effects, mood changes, changes in dyskinesia percentage, early morning dystonia and off period percentage were also noted. This study suggests improvement in the above parameters with minimal side effects. PMID- 1452558 TI - Arrhythmias and conduction defects in patients with mitral valve prolapse: a study based on ambulatory monitoring and electrophysiologic studies. AB - Twenty consecutive symptomatic patients of mitral valve prolapse (MVP) and 20 normal age, sex and symptom matched controls were studied. Ambulatory monitoring studies revealed the presence of atrial premature beats (APC) in 16 subjects in each group. Isolated ventricular premature beats (VPC) were observed in 12 patients with MVP and 15 subjects in control group (p = ns). Complex VPCs (Lown IVa, IVb) were recorded in 4 patients of MVP vs 3 controls (p = ns). There was no correlation between the occurrence of arrhythmias with the degree of MVP or the degree of mitral regurgitation. Likewise, MVP patients with prolonged QTc interval did not show higher incidence of spontaneous arrhythmias when compared to those with normal QTc interval. Nineteen patients underwent electrophysiological studies. Two patients showed evidence of abnormal sinus node function. Both these patients in addition had AV nodal abnormalities, manifested by prolonged AH interval. Programmed stimulation studies induced AV nodal tachycardia in one and non-sustained ventricular tachycardia in two (polymorphic in one and monomorphic in the other). Ambulatory monitoring in both these patients did not show any evidence of complex VPCs or VT, indicating poor correlation between inducibility and presence of spontaneous complex VPCs. Patients with MVP do not have a higher prevalence of spontaneous atrial or ventricular arrhythmias when compared to matched normal controls with similar symptomatology. The presence of mitral regurgitation, severity of MVP and associated prolonged QTc interval is not associated with higher prevalence of arrhythmias. The correlation between spontaneous and inducible arrhythmias is poor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452559 TI - Subclavian vein catheters for haemodialysis with and without a subcutaneous tunnel. AB - We have retrospectively analysed the usefulness of a subcutaneous tunnel in patients undergoing haemodialysis through a double lumen subclavian catheter; 194 catheters were used in 145 patients. In 105 patients a subcutaneous tunnel was created. Entry site infection was significantly higher in the no tunnel group (30%; P < 0.02). There was no statistically significant difference in the incidence of septicaemia in the two groups. Eighty five percent of episodes of septicaemia and 67% of entry site infections were due to Staphylococcus aureus. All responded to removal of the catheter and to antibiotics. The average duration the catheter was in place was 20.39 and 21.94 days in the groups with and without tunnel respectively. The average number of dialyses was 9.13 and 9.33 per catheter in the tunnel and no tunnel groups respectively. Three patients had pneumothorax. Subclavian vein thrombosis was suspected clinically in 3 cases. There was no catheter related mortality. We concluded that while entry site infection occurred more frequently in the no tunnel group, the overall incidence of septicaemia was not different in the two groups. Creation of a subcutaneous tunnel has no added advantage. PMID- 1452561 TI - A critical review of prescriptions in internal medicine. AB - A study was undertaken to assess the prescribing trends in inpatients of the Internal Medicine Department of Government General Hospital which is attached to Guntur Medical College, Guntur. Prescriptions for 250 patients were audited under various heads like details of drugs used, generic versus trade name prescribing, dosage, dosage form, dose interval, drug of choice and duration of treatment. Among 250 prescriptions audited, 7 percent used generic names, 22 percent trade names, and 71 percent combinations of both generic and trade names. Dosages and dosage intervals were appropriate. In 75 percent of the audited cases, the duration of treatment was appropriate; 25 percent did not specify the duration. The choice of drugs was proper in 84 percent and inappropriate in 16 percent of cases. Certain deficiencies in the prescribing trends are analysed. PMID- 1452560 TI - Betamethasone in tetanus patients: an evaluation of its effect on the mortality and morbidity. AB - The effect of betamethasone on the outcome in moderate to severe tetanus was studied in a randomised, double blind, placebo controlled study in 22 patients. The mortality rate was reduced by 36.1% with the addition of corticosteroids to the regime of treatment. Betamethasone did not alter the duration of intensive care in those requiring it, but reduced the need for tracheostomy and ventilation. The mean daily dose of diazepam required was not significantly different between the two groups and there was no increase in the incidence of infections in the betamethasone group. PMID- 1452562 TI - Atypical presentations of falciparum malaria. AB - To identify the uncommon presentations of falciparum malaria in an endemic area and to assess the outcome of treatment, a study was carried out on 35 proved cases whose clinical presentations were either dominated by features other than fever or the history of fever was totally absent. Both urban and rural patients were included. Seventeen cases (48.3%) presented with features of cerebral malaria. Acute abdomen, urticaria, and unexplained shock were the other atypical presentations. Five cases (14.3%) of cerebral malaria died. We conclude that awareness of atypical presentations is important to detect cases of falciparum malaria in an endemic area. Intravenous quinine may need to be given promptly even when cerebral malaria is diagnosed empirically. PMID- 1452563 TI - Study of foetal antigen in haematological malignancy. AB - Forty patients with different varieties of leukaemia and lymphoma were studied before and after therapy. Red cells and lymphocytes from each patient were tested for foetal antigen by lectin-agglutination test. The antigen was detectable on red cells in all untreated cases, the highest titre being found in chronic myeloid leukaemia. The titre showed significant reduction after treatment in all cases. We conclude that foetal antigen on red cells is a useful diagnostic aid in haematological malignancy and is a good indicator of the outcome of therapy. PMID- 1452564 TI - Diagnostic evaluation of ascitic adenosine deaminase activity in tubercular peritonitis. AB - Activity of adenosine deaminase (ADA) in serum and peritoneal fluid was studied prospectively in 24 aetiologically proved cases of ascites and 10 age-matched controls. Patients were divided into 3 groups according to causes of ascites, viz. malignant ascites (11), tubercular peritonitis (7) and cirrhosis of liver (6). Serum ADA values and peritoneal: serum ADA ratio did not show any consistent pattern in any group. But in patients with tubercular peritonitis ADA activity in ascitic fluid was significantly higher (P < .001) than in the other groups. An ascitic ADA level of 30 units/L had a sensitivity of 100% and specificity of 94.1% for tubercular peritonitis. These findings suggest that the ascitic fluid ADA activity is useful for the diagnosis of tubercular peritonitis; this method is simple and least invasive. PMID- 1452565 TI - Prevalence of hepatitis surface antigen among rural population of Loni area in Ahmednagar district of Western Maharashtra. AB - Three hundred and fifty three subjects among the rural population of Loni area admitted in the hospital, and 188 medical staff members working in the Rural Medical College and Hospital, Loni, were screened for the presence of HBsAg. Reveresed passive haemagglutination assay was used for screening; it showed an HBsAg positivity rate of 21.8% and 15.8% among hepatitis and non hepatitis cases respectively, and 1.2%, 0% and 4.2% among medical students, doctors and nursing staff respectively. A high HBsAg positivity rate has been observed in the rural population of Loni area. PMID- 1452566 TI - Pharmacokinetics of antiepileptic drugs and its application to therapeutics. PMID- 1452567 TI - Aluminium phosphide poisoning: present status and management. PMID- 1452568 TI - Current molecular techniques and strategies for gene localization. PMID- 1452569 TI - Pneumocystis carinii pneumonia in untreated acute non-lymphoblastic leukaemia. AB - Mixed opportunistic infection with Pneumocystis carinii and Candida prior to cytotoxic therapy in a young male diagnosed as having acute non-lymphoblastic leukaemia resulted in early catastrophe. The role of awareness of this complication and its prompt management is discussed. PMID- 1452570 TI - Primary sclerosing cholangitis. AB - A case of primary sclerosing cholangitis is reported. There was no history of choledocholithiasis, operation or traumatic biliary injury. PMID- 1452571 TI - Pulsus paradoxus with tense pleural effusion. PMID- 1452572 TI - Paraneoplastic syndromes: fads and facts (1) and neurological manifestations of malignant diseases (2) PMID- 1452573 TI - Chloramphenicol resistant typhoid fever. PMID- 1452574 TI - An outbreak of multidrug resistant typhoid fever in Nagpur. PMID- 1452575 TI - Drug resistant typhoid fever (DRT) PMID- 1452576 TI - Routine use of ciprofloxacin. PMID- 1452577 TI - Is ciprofloxacin a panacea or do we need a 'use-restricted' drug? PMID- 1452578 TI - Ciprofloxacin induced psychosis. PMID- 1452579 TI - Treatment of acute viral hepatitis with ribavirin. PMID- 1452580 TI - Seventh cranial nerve palsy in a case of viral hepatitis (type B) PMID- 1452581 TI - Therapy of enteric fever. PMID- 1452582 TI - Burn rehabilitation: our unanswered challenge. The 1992 presidential address to the American Burn Association. PMID- 1452583 TI - Decreased pulmonary barotrauma with the use of volumetric diffusive respiration in pediatric patients with burns: the 1992 Moyer Award. AB - Pulmonary barotrauma is a frequent, life-threatening complication in the pediatric patient who is treated with mechanical ventilation. The volumetric diffusive respiration (VDR) ventilator, which employs a high-frequency progressive accumulation of subtidal volume breaths in a pressure-limited format with a percussive waveform, is capable of providing adequate gas exchange at lower airway pressures; this theoretically decreases the incidence of pulmonary barotrauma compared with conventional mechanical ventilation (CV). The incidence of pulmonary barotrauma since 1988 was evaluated in pediatric patients with burns who were younger than 2 years of age. Twenty-four patients who were treated with only CV were compared with 15 patients who were treated with only VDR. Pulmonary barotrauma was defined as the development of pneumothorax, pneumomediastinum, pneumopericardium, or pneumoperitoneum. There were no significant differences between CV-treated and VDR-treated groups (mean +/- SEM) in the patient characteristics of age (15.9 +/- 1.3 months vs 16.6 +/- 1.8 months), weight (11.2 +/- 0.5 kg vs 12.5 +/- 0.7 kg), percent total body surface burn (46.2% +/- 4.9% vs 55.6% +/- 6.2%), percent full-thickness burn (38.1% +/- 5.3% vs 50.0% +/- 6.6%), inhalation injury (40% vs 60%), or total number of days that mechanical ventilation was required (18.2 +/- 4.2 days vs 22.4 +/- 5.9 days); although these parameters show a slightly more severe degree of injury in the VDR-treated group. There was a reduction in the incidence of pulmonary barotrauma when VDR was used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452584 TI - Pseudomonas aeruginosa exotoxin A: its role in retardation of wound healing: the 1992 Lindberg Award. AB - Bacterial concentrations greater than 10(5) colony-forming units/gm of tissue prevent wound healing. However, it has not been determined whether it is the number of bacteria or a toxin produced by these organisms that impedes the wound healing process. Pseudomonas aeruginosa (PSAR), a burn wound pathogen, produces a dermonecrotic toxin, exotoxin A. Studies have indicated a role for exotoxin A in the pathogenicity of PSAR. We investigated the role of exotoxin A in the retardation of contraction. Acute granulating wounds were created on 90 Sprague Dawley rats. The animals were equally divided into six groups and were treated topically as follows: group 1, sham: no infection, no treatment; group 2, exotoxin A; group 3, exotoxin A and antiexotoxin; group 4, autoclaved PSAR 10(6); group 5, 10(6) viable PSAR inoculated in the wound; group 6, 10(6) viable PSAR and antiexotoxin. Wound contraction was measured with the use of planimetry twice a week. Serial biopsies were performed on all wounds. Contraction rates revealed significantly (p < 0.05) retarded closure in the animals treated with exotoxin A and in the viable PSAR group when compared with the rates of the noninfected control groups. Animals treated with exotoxin A plus antiexotoxin A and those treated with live PSAR and antiexotoxin showed contraction rates identical to the control groups. These data suggest that exotoxin A in PSAR infections retards wound healing and that neutralization of the toxin restores the normal healing process. PMID- 1452585 TI - Clinical trials of a living dermal tissue replacement placed beneath meshed, split-thickness skin grafts on excised burn wounds. AB - We evaluated the ability of Dermagraft (Advanced Tissue Sciences, La Jolla, Calif.), a living tissue analog that is composed of human neonatal fibroblasts, which are grown on a polyglactin acid Vicryl mesh (Ethicon Inc., Somerville, N.J.), to function as a dermal replacement when placed beneath meshed, expanded split-thickness skin grafts (MESTSGs). Full-thickness burn wounds in 17 patients with burns (mean age, 31 years; range, 6 to 69 years; mean burn size, 23.8% total body surface area) were excised to subcutaneous fat (nine patients), to fascia (three patients), or to a combination of deep dermis and fat (five patients). Dermagraft was placed over the experimental sites, which were then covered with MESTSGs. Paired control sites on each patient received MESTSGs only. The results showed that "take" of MESTSGs on control sites was slightly better than take on experimental sites that contained the Dermagraft; however, the differences were not statistically significant. Mesh interstices epithelialized over the surface of the full-thickness wound (control sites) or over the surface of Dermagraft (experimental sites). Wound biopsy specimens demonstrated no evidence of rejection of the cultured allogeneic fibroblasts and minimal inflammatory reaction to the Vicryl fibers. Evidence of continuous basement membrane formation at the epithelial-Dermagraft junction, which was identified by immunohistochemical staining for laminin and type IV collagen, was seen by day 14 beneath the healed epithelium in the skin graft interstices. The Vicryl fibers were hydrolyzed in the wound over a 2-to-4-week period, although some expulsion of fibers occurred as the healing epithelium advanced to close the MESTSG interstices. Elastic fibers were not seen in neodermal tissue in either control or experimental wounds at periods of up to 1 year after grafting. Further trials with this living tissue replacement are in progress. PMID- 1452586 TI - Efficacy of leupeptin, superoxide dismutase, and verapamil in modulating delayed reperfusion damage after burn injury. AB - Reperfusion damage has been identified as an important factor in multiorgan failure after severe burn injury. We wondered if leupeptin, a protease inhibitor, superoxide dismutase (SOD), a scavenger of free oxygen radicals, or verapamil, a calcium antagonist, would protect the cellular energy metabolism when they were given with fluid resuscitation that was delayed 6 hours after a severe burn injury. Fifty male rats weighing 280 to 300 gm received a 50% third-degree scald burn. Ten of these received fluid resuscitation at 30 minutes and 1 1/2 hours after injury, and 40 received delayed fluid resuscitation at 6 and 7 hours after injury. Thirty of these 40 rats were given leupeptin (n = 10), SOD (n = 10), or verapamil (n = 10). Heart, liver, and kidney tissue samples were obtained 8 hours after injury; adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate were measured; and the energy charge potential was calculated. Tissue water content (TWC) in lung and skeletal muscle was also determined. The adenine nucleotide pool and the energy charge potential in heart, liver, and kidney tissue were all significantly decreased (p < 0.01) in rats receiving delayed fluid resuscitation compared with those receiving early resuscitation. Leupeptin was effective in protecting the heart against reperfusion damage, and verapamil and leupeptin showed some efficacy in protecting kidney tissue. Liver tissue, however, showed no protective response with therapy. TWC was significantly decreased (p < 0.01) in skeletal muscle with SOD treatment, and though all treatments appeared to keep lung water content reduced, none was significant at p < 0.01. We thus conclude that both the decreases in heart and kidney adenine nucleotides and the increase in TWC that are caused by delayed fluid resuscitation can be attenuated with appropriate pharmacologic agents. PMID- 1452587 TI - Effect of indomethacin and Impact liquid diet administration on inflammatory mediator production by murine splenocytes after burn injury. AB - Production of prostaglandin E2 (PGE2) and tumor necrosis factor-alpha (TNF-alpha) by various cells is increased after injury, and these mediators are implicated in the downregulation of immune responses. We attempted to modulate the production of immune suppressive mediators by inhibiting prostaglandin production in a murine model that had a burn covering 25% of the total body surface area. Two treatments were performed. One was the intraperitoneal administration of indomethacin after burn injury at 2 mg/kg day for 10 days. The control group received saline solution injections. The other treatment was the ad libitum administration of a commercial diet after burn injury for 10 days. This diet contained mixed fats, including omega-3 and omega-6 fatty acids. The control group received standard mouse food. On days 1, 5, and 10 after burn injury, spleens were removed aseptically, and splenocyte cultures were established and stimulated with phytohemagglutinin. TNF-alpha and PGE2 concentrations were determined in culture supernatants at 48 hours with the use of commercial enzyme linked immunosorbent assay kits. Splenocytes from burned animals produced elevated levels of both mediators in culture supernatants, reaching significant levels of TNF-alpha on day 10 after burn injury and of PGE2 on days 5 and 10 after burn injury. Neither the administration of indomethacin for 10 days nor the administration of the commercial diet for 10 days decreased production of these mediators in culture. However, cells in culture may escape the in vivo regulating effects of biologic modifying agents. PMID- 1452588 TI - Modification of calcium flux of twitch skeletal muscle in mice subjected to 20% body surface area burn. AB - One systemic effect of burn trauma is skeletal muscle weakness. This is the result of changes in second messenger systems involving calcium (Ca2+). Kinetic analysis of Ca2+ from cellular compartments of skeletal muscle of mice that were subjected to small burn injury (20% body surface area) was performed. Muscles of the burn group showed an increased 45Ca2+ uptake maxima compared with those of time-matched control groups. Also, 45Ca2+ efflux analysis showed a lack of differentiation between electrically stimulated tissues and nonstimulated tissues that was easily observed in time-matched control groups. This lack of differentiation indicated changes in intracellular compartmentation. It can be speculated that burn trauma may have a regulatory role in the excitation contraction coupling mechanism by altering myoplasmic levels of Ca2+ even before skeletal muscle dysfunction occurs. These findings suggest that agents capable of controlling myoplasmic Ca2+ levels may aid in alleviating chronic skeletal muscle dysfunction in patients with burns. PMID- 1452589 TI - Micrografts: the "super" expansion graft. AB - A novel technique for producing micronized skin grafts that was introduced in a paper presented at the 1990 ABA meeting was evaluated to quantify maximum expansion. Twenty Sprague-Dawley rats were divided into two groups representing 10:1 and 25:1 expanded micrograft ratios, respectively. Grafted sites in both groups were shown to heal better than those of the control group, and both grafted groups showed comparable healing at day 10. PMID- 1452590 TI - Effects of high-dose vitamin C administration on postburn microvascular fluid and protein flux. AB - The effects of vitamin C treatment (14 mg/kg/hr) on burn injury were evaluated in the hind paws of 12 mongrel dogs. A lymph duct above one hind paw of each dog was cannulated. Hourly lymph flow rates (QL) and plasma and lymph total protein concentrations were measured before the burn injury and for 6 hours after the burn injury. Data from 24 paws were divided into four groups: nonburn without treatment, nonburn with treatment, burn without treatment, and burn with treatment. The nonburn groups showed no significant differences in QL or in total protein flux. In the burn groups the postburn hourly QL increased by sevenfold in the nontreatment group and only by threefold in the treatment group, whereas the postburn hourly total protein flux increased by fifteenfold and fivefold, respectively. We conclude that administration of high-dose vitamin C reduces early postburn microvascular leakage of fluid and protein. PMID- 1452591 TI - How long do we need to give antioxidant therapy during resuscitation when its administration is delayed for two hours? AB - Twenty-four guinea pigs with third-degree burns over 70% of the body surface area were divided equally into four groups. All animals received Ringer's lactate (R/L) beginning 30 minutes after burn injury. Group 1 received R/L without vitamin C beginning 2 hours after burn injury. Groups 2, 3, and 4 received R/L with vitamin C until 4, 8, and 24 hours after burn injury, respectively. Beginning 3 1/2 hours after burn injury the hourly fluid volume was reduced to 25% of the Parkland formula calculation. The hourly sodium and fluid intake in each group was the same. Groups 1 and 2 demonstrated higher hematocrit and lower cardiac output values as compared with those values for group 3, indicating hypovolemia and hemoconcentration in these groups. Group 3 showed hematocrit and cardiac output values equivalent to those values for group 4. We conclude that high-dose vitamin C must be given until 8 hours after burn injury to maintain adequate hemodynamic stability in the presence of a reduced resuscitation fluid volume. PMID- 1452592 TI - Inhalation injury: a decade without progress. AB - Despite major advances in the management of patients with critical burn injuries, inhalation injury continues to be a major determinant of death resulting from burn injuries. Two cohort groups of victims with burn and inhalation injuries, separated by a decade, were retrospectively reviewed in an effort to determine the impact of newer treatment modalities. Patients were categorized as being at "high" or "low" risk on the basis of primary and secondary diagnostic criteria. Despite a statistically significant decrease in the percent of total body surface injury, no change in mortality rate was noted between the two groups. The advent of sophisticated diagnostic and management techniques does not appear to have decreased the mortality rate associated with inhalation injury. PMID- 1452593 TI - A distraction technique for control of burn pain. AB - Research has indicated that analgesics alone do not adequately relieve pain for 75% of patients with burns. The purpose of this study was to determine the effects of a distraction therapy, in which videos were used in combination with administration of analgesics, on intensity and quality of pain and on levels of anxiety in adults during burn dressing changes. The sample consisted of 17 patients who were randomly assigned to the treatment or the control group. The treatment group viewed video programs that were composed of scenic beauty accompanied by music. Each was asked to score his or her present pain intensity and pain rating index with the McGill questionnaire and anxiety with the Spielberger questionnaire before and after the dressing change. A nested general linear model using the "F" test in multiple regression analysis was adjusted for age, percent partial-thickness burn, and choice of topical agent demonstrated that the use of videos during the dressing changes significantly reduced pain and anxiety: present pain intensity (F = 8.69; p = 0.01), pain rating index (F = 5.57; p = 0.03), anxiety (F = 9.10; p = 0.01). It is recommended that the use of pain medication be augmented by use of videos during burn dressing changes. PMID- 1452594 TI - Use of morphine sulfate (MS Contin) in patients with burns: a pilot study. AB - Morphine sulfate (MS Contin), a proven analgesic in the treatment of cancer pain and chronic benign pain, seems to be a good analgesic for the treatment of burn pain. MS Contin is morphine sulfate incorporated in a wax cellulose matrix delivery system. This wax cellulose delivery system gives MS Contin its duration of action. Ten patients were enrolled in an open-labeled, nonrandomized study. The study was designed to examine the analgesic efficacy of MS Contin in the burn population. Each patient remained in the study for 6 days. The efficacy of the analgesic regimen was subjectively measured by the visual pain scale. The MS Contin group was retrospectively compared with a group of patients who were given continuous intravenous infusions of morphine. The two groups were matched according to age, burn size, surgical procedures, and hospital stay. The analgesic qualities of MS Contin were comparable to those of continuous intravenous morphine sulfate infusions. MS Contin is a possible candidate for the treatment of patients with burn pain because of its analgesic qualities, oral dosing, and duration of action. PMID- 1452595 TI - Updating upper extremity temporary prosthesis: thermoplastics. AB - Since 1989 amputees with upper-extremity burns have been fitted with a temporary prosthesis fabricated from low-temperature thermoplastic. Before 1989 conventional temporary prostheses were fabricated with plaster. The use of the thermoplastic material has produced a lightweight, cost-effective, modular system. No patients exhibited skin breakdown with the thermoplastic material. It appears that thermoplastics may be the next major breakthrough in terms of a design for a temporary upper-extremity prosthesis. PMID- 1452596 TI - Mixing inpatient with outpatient care: establishing an outpatient clinic on a burn unit. AB - Outpatient care of patients with burns is an important aspect of a total health care plan. Changes in the health care system, which focuses on cost containment, force reevaluation of the methods used for delivery of high-tech care, particularly in areas such as burn care. Great advances that have taken place over the past decade in the field of burn care have enabled health care providers to treat more patients with burns as outpatients. Those who are specially trained in burn care continue to be the optimal caregivers. The appropriate facilities, spray tables, hydrotherapy, and dressing rooms in which patients with burns are treated are equally important and must be adapted to meet the needs of patients who are ambulatory. The goals of an outpatient burn clinic should be to provide daily wound care and patient education to prevent unnecessary admissions and to promote early discharge for hospitalized patients. Nurses trained in burn care are the optimal providers of ambulatory burn care; therefore the clinic location should be where the caregivers are available. Several obstacles needed to be overcome before an outpatient clinic could be established on the burn unit itself. Wound care is now provided by burn unit nurses, which leads to better results and more consistent follow-up. Patient satisfaction is increased, patient teaching is provided by experienced staff, unnecessary admissions are prevented, and patients are able to be discharged from the hospital earlier or to be followed as outpatients even if surgery is eventually required. PMID- 1452597 TI - Color pressure garments versus traditional beige pressure garments: perceptions from the public. AB - Social acceptance of patients with burns may be affected by the color of the pressure garment they wear. The purpose of this study was to ask students (n = 712), health care providers (n = 354), and the public (n = 250) their perceptions of beige versus color pressure garments. It was assumed that beige pressure garments have negative connotations and that colored pressure garments have positive connotations. Data were collected from subjects after they viewed beige, pink, and blue pressure garments. Items on the instrument contained bipolar word pairs rated on a 5-point scale; a rating of 1 indicated positive feelings, and a rating of 5 indicated negative feelings. Cronbach's alpha reliability for the instrument was 0.85, indicating a high internal consistency among items. Paired t test indicated a significant difference between the subjects' perceptions of the beige garments versus their perceptions of the color garments (t = -44.82, p = 0.000) among all subjects (n = 1259). Results indicate that positive feelings toward color garments may lead to social acceptance of the patient with burns, which in turn could increase the patient's self-esteem. PMID- 1452598 TI - Burn center reimbursement analysis. AB - If burn centers are to survive in the current fixed-payment environment, managers and physicians must be knowledgeable of the parameters and regulators of reimbursement. The purpose of this study was to assess the reimbursement status of a burn center in a private, not-for-profit facility. The analysis included both internal and external constraints imposed on the hospital. Data from fiscal year 1989-90 were used to identify the most frequently coded burn diagnosis related groups and third-party payers. Actual reimbursement rates per diagnosis related group were examined, and the average charge per patient discharge was compared with reimbursement per patient. Total billed charges versus received revenue for Medicaid patients were explored. Problems and solutions were identified and discussed after completion of the assessment. PMID- 1452599 TI - When is enough enough? Ethical dilemmas on the burn unit. AB - Modern burn care often leads to the dilemma of what should or should not be done for patients with clinical deterioration and organ system failure who fail to respond to therapy. The questions are, "When is enough enough?" and "Who decides?" We have developed a structured conference to address these issues and to help us decide whether to recommend continued invasive diagnostic and therapeutic intervention or to allow the patient to "die with dignity." This conference can be requested by any member of the burn team who feels uncomfortable with what is being done for and/or to a patient. It is a meeting of the entire team, and its purpose is to discern the judgment of the group. When the consensus decision is to forego additional therapy, the decision is then presented to the patient (if he or she is able to understand and respond) and to the patient's family. The decision made by the group removes the responsibility of any individual from making a stressful decision if the patient's condition deteriorates abruptly. Patients who accept this decision exhibit a peaceful calm that invariably reaffirms the group dynamics. The family often experiences a great deal of relief, because they are not forced to make the decision even though they wanted it made. Inviting nurses to be active participants in the decision process builds their personal and professional self-esteem and binds the team members into a more tightly knit community. The attending staff may perceive this process as an abdication of responsibility; however, in our experience the consensus conference has led to a conviction that the wisdom of the team is always best. PMID- 1452600 TI - NSAID-induced gastroenteropathy: a biochemical dissection. AB - The most widely accepted view is that damage to the mucosa sets the stage for lesions related to NSAIDs. An alternative hypothesis is that NSAID-induced damage to GI microvasculature is the primary pathologic event. PMID- 1452601 TI - SI units: wrong for the right reasons. PMID- 1452602 TI - Wrong impression. PMID- 1452603 TI - Acute MI pattern in diabetic ketoacidosis. PMID- 1452604 TI - Palpable purpura: identifying the cause. PMID- 1452605 TI - Liposomes: realizing their promise. AB - Thirty years of study have proved that these artificial organelles are versatile tools for learning about the cell membrane. Researchers are now actively investigating their potential for some interesting practical uses as vehicles for gene transfer, as artificial erythrocyte surrogates, as a lubricant for degenerated joint surfaces, and most imminently as "targeted carriers" of pharmacologic agents. PMID- 1452606 TI - Thromboembolism and prosthetic heart valves. PMID- 1452607 TI - Determination of fatty acid and triacylglycerol composition of human adipose tissue. AB - The fatty acid composition of adipose tissue was studied in a population in western Andalusia with a diet in which the fat contribution is mainly from olive oil. The lipid composition of adipose tissue, including the fatty acid composition of triacylglycerols, was examined by capillary gas chromatography. Thirty-five peaks were resolved, ranging in chain length from 12 to 24 carbon atoms, including geometric and positional isomers. The major triacylglycerol was POO, followed by PLO and OOO. PMID- 1452608 TI - Application of gas chromatography-mass spectrometry with selected ion monitoring to the urinanalysis of 4-pyridoxic acid. AB - An analytical protocol has been developed for the analysis of urinary 4-pyridoxic acid (4-PA) by gas chromatography-mass spectrometry (GC-MS) for use in metabolic studies. Aliquots of urine were deproteinised and fractionated by isocratic reversed-phase high-performance liquid chromatography. The eluent fraction containing the 4-PA was collected, freeze-dried and silylated using N-methyl-N (tert.-butyldimethylsilyl)trifluoroacetamide. Derivatisation produced the mono tert.-butyldimethylsilyl derivative of 4-PA lactone. This derivative was readily amenable to GC-MS analysis in the electron ionisation (70 eV) mode, yielding a prominent fragment ion at m/z 222 ([M-57]+; base peak). A heavy isotope-labelled derivative of pyridoxine [dideuteriated pyridoxine; 3-hydroxy-4-(hydroxymethyl)-5 [hydroxymethyl-2H2]-2-methylpyridine] has been synthesised and is being employed to determine the kinetics of labelling of the body pools of vitamin B6. Kinetic measurements are based on the determination of the relative proportions of metabolically produced deuterium-labelled and non-labelled 4-PA in urine, obtained from stable isotope ratios determined by low-resolution selected ion monitoring using a bench-top quadrupole GC-MS system. PMID- 1452609 TI - Characterisation of oligosaccharides from a glycoprotein variant of human serum albumin (albumin Casebrook) using high-performance anion-exchange chromatography and nuclear magnetic resonance spectroscopy. AB - The characterisation of oligosaccharides present on albumin Casebrook, a glycoprotein variant of human serum albumin, which contains an N-linked oligosaccharide at an attachment site formed by a point mutation of 494 Asp- >Asn, is described. The monosaccharide compositional analysis of purified glycopeptides suggested the presence of complex biantennary carbohydrate structures. The oligosaccharides which were released by N-glycosidase-F appeared to be a single molecular species according to their retention on high-performance anion-exchange chromatography. The structure of the oligosaccharide was suggested by sequential exoglycosidase digestions and confirmed by proton nuclear magnetic resonance spectroscopy. It was concluded that the oligosaccharides were essentially homogeneous and consisted of an alpha(2-6)-desialylated complex biantennary glycan. PMID- 1452610 TI - Gas chromatographic-mass spectrometric method for routine monitoring of 5 fluorouracil in plasma of patients receiving low-level protracted infusions. AB - A gas chromatographic-mass spectrometric (GC-MS) method is described which quantitates 5-fluorouracil (5-FU) plasma levels ranging from 0.5 to 50 ng/ml. The analysis uses two internal standards, 1,3-[15N2]-5-fluorouracil and 5 chlorouracil. Extraction and derivatization of the pyrimidine bases were accomplished in a single step using acetonitrile. Compounds were analyzed as their 1,3-dipentafluorobenzyl derivatives by electron-impact MS, and the GC-MS analysis was automated with respect to sample injection and data reduction. Stability of the analysis was demonstrated by continuous unattended analysis of 5 FU in human plasma for periods of up to three days with no deterioration of the quantitative results. The method is applicable to quantitating 5-FU plasma levels in patients receiving protracted infusions of the drug for colorectal cancer or other malignancies. PMID- 1452611 TI - Identification of metabolites of halofantrine, a new candidate anti-malarial drug, by gas chromatography-mass spectrometry. AB - Two previously unknown metabolites of halofantrine, a candidate anti-malarial drug, have been isolated by thin-layer chromatography from the plasma of dogs administered a single oral dose of 60 mg/kg. Their identifies were investigated after trimethylsilylation by gas chromatography-mass spectrometry under electron impact and negative-ion chemical ionization conditions. The structural assignment was further confirmed by using a combination of elemental composition analysis of all the isotope peaks at low mass resolution and isotope pattern matching. These two metabolites were formed by modification of the dibutylaminopropyl side-chain of the parent compound involving deamination and oxidation or reduction. PMID- 1452612 TI - Comparison of high-performance liquid chromatography and high-performance capillary electrophoresis for the determination of cicletanine in plasma. AB - A sensitive and selective high-performance capillary electrophoresis (HPCE) procedure was developed for the determination of total cicletanine in human plasma. The procedure consisted in extraction of the drug with diethyl ether and analysis by micellar electrokinetic capillary chromatography in a fused-silica capillary using sodium dodecyl sulphate in the run buffers and ultraviolet detection. The concentrations of cicletanine obtained by this method were compared with those obtained by a high-performance liquid chromatographic (HPLC) method used routinely. The within-run precision of the methods, expressed as relative standard deviation, ranged from 1.6 to 7.8% for HPLC and from 6.4 to 11.1% for HPCE. Both methods showed an adequate level of accuracy; the relative errors ranged from 0.02 to 3.25% for HPLC and from 0.21 to 2.90% for HPCE. The HPCE method required less than half the time taken by the HPLC method, making HPCE a useful alternative technique for the routine determination of cicletanine in plasma. Both methods were used to follow the time course of total cicletanine in human plasma after a single oral therapeutic dose of the drug. PMID- 1452613 TI - Determination of picogram levels of heptylphysostigmine in human plasma using high-performance liquid chromatography with fluorescence detection. AB - A sensitive (50 pg/ml) method for the determination of heptylphysostigmine in human plasma is described. The procedure is based on liquid-liquid extraction of the drug from buffered plasma, and analysis of the concentrated organic extract using high-performance liquid chromatography on a silica column, under normal phase chromatographic conditions, with fluorescence detection. Physostigmine was used as an internal standard. The assay has been fully validated in the concentration range 50-2000 pg/ml and utilized for the analysis of clinical samples from subjects dosed with heptylphysostigmine. PMID- 1452614 TI - Determination of zolpidem, a new sleep-inducing agent, and its metabolites in biological fluids: pharmacokinetics, drug metabolism and overdosing investigations in humans. AB - For the determination of zolpidem, a new sleep inducer, and its metabolites in human plasma and urine, three methods were developed that are suitable for pharmacokinetics, drug metabolism and overdosing investigations. The methods used for pharmacokinetic and drug metabolism studies are based on column-switching high-performance liquid chromatography; they do not require any sample manipulation because the plasma or diluted urine is injected into a pre-column where clean-up and preconcentration take place. The analytes are transferred by valve-switching to the C18 analytical column for chromatography. To investigate overdose cases, urine samples only are used: the method is simple, because the diluted urine can be injected directly into the analytical column (phenyl type). This allows the identification and quantification of the principal urinary metabolite of zolpidem, the unchanged drug being practically undetectable. All the methods use fluorescence detection, which affords high sensitivity and selectivity. It is necessary to use a method capable of the determination of metabolites even if these are apparently pharmacologically inactive, because in different physiopathological populations the qualitative and quantitative metabolic profiles of zolpidem could be different. The method designed for the investigation of (accidental or deliberate) overdose cases is, as required on such occasions, simple and rapid, with good selectivity with respect to commonly prescribed psychotropic drugs. PMID- 1452615 TI - High-performance liquid chromatographic determination of ambroxol in human plasma. AB - Ambroxol has been determined in biological fluids using a rapid and sensitive high-performance liquid chromatographic method. The samples prepared from plasma by liquid-liquid extraction were analysed on reversed-phase silica gel by competing-ion chromatography with ultraviolet detection. The method was applied to the determination of ambroxol levels in twelve healthy volunteers after oral administration of 90 mg of ambroxol in tablets of Mucosolvan and Ambrosan. PMID- 1452616 TI - Coupling of microdialysis with capillary electrophoresis: a new approach to the study of drug transfer between two compartments of the body in freely moving rats. AB - The feasibility of in vivo microdialysis and capillary electrophoresis for pharmacokinetic studies was tested. Microdialysis probes were inserted in the jugular vein and brain of rats. After an intraperitoneal injection of phenobarbital, microdialysis was performed in the brain and the blood simultaneously in each rat under freely moving conditions. Capillary electrophoresis with ultraviolet absorption was used to measure phenobarbital in blood and brain dialysates. The time course of phenobarbital in the blood and in the extracellular space of the brain was followed. The results demonstrated that microdialysis can be used for pharmacokinetic studies in freely moving animals. Capillary electrophoresis has the potential to improve the time resolution of microdialysis. Other advantages of microdialysis and capillary electrophoresis for pharmacokinetic studies are discussed. PMID- 1452617 TI - Fluorimetric detection of serum corticosterone using high-performance liquid chromatography. AB - A simple, sensitive, specific and reproducible method for the determination of corticosterone concentrations in rat serum using high-performance liquid chromatography (HPLC) with fluorimetric detection is described. Corticosterone is detectable down to 0.1 ng injected onto the HPLC column. Cortisol is used as an internal standard. Ethyl acetate was used for both initial serum corticosteroid extraction and the subsequent fluorophore extraction after sulfuric acid hydrolysis; thus sulfuric acid does not enter the HPLC system. The resultant fluorophores for both corticosterone and cortisol are stable for at least two weeks at ambient temperature not requiring storage at -20 degrees C. The procedure is highly suitable for use with HPLC systems utilising automatic sample injectors. The method is specific for corticosterone; dexamethasone, cortisone and gonadal steroids are not detectable and do not interfere in this assay. PMID- 1452618 TI - Determination of urinary 3-methylhistidine by high-performance liquid chromatography with o-phthaldialdehyde precolumn derivatization. AB - A high-performance liquid chromatographic method to measure the concentration of 3-methylhistidine in human urine with o-phthaldialdehyde precolumn derivatization is described. A clear separation of the 3-methylhistidine derivative from other derivatives in urine was achieved within 25 min. The linearity, recovery and coefficients of variation were determined. The method was successfully applied to clinical assays and used for diagnostic purposes. PMID- 1452619 TI - Assay of timolol in human plasma using gas chromatography with electron-capture detection. AB - A simple and sensitive gas chromatographic method has been developed for the determination of timolol in plasma using electron-capture detection and propranolol as internal standard. Timolol was extracted using butyl chloride and derivatized using trifluoroacetic anhydride in butyl acetate. The lower detection limit for the assay was found to be 1 ng/ml from 1 ml of plasma. Extracted standards gave within-day precision of 12.55, 9.68 and 3.78% for 1, 20 and 100 ng/ml plasma samples, respectively. A recovery of at least 80% of timolol was found using the extraction method described. The assay was used in a randomized cross-over bioequivalence trial using an oral administration of 20 mg of timolol. Pharmacokinetic parameters compare favourably with other literature values. PMID- 1452620 TI - Analysis of 5-fluorouracil in plasma and urine by high-performance liquid chromatography. AB - A relatively simple, sensitive and rapid high-performance liquid chromatographic method is described for measuring the anticancer drug 5-fluorouracil (5-FU) in human plasma and urine. The procedure includes liquid-liquid extraction using ethyl acetate-methanol (95:5) and preparative column chromatography to separate 5 FU from constituents normally occurring in these biological samples. The columns contained a specially modified form of diatomaceous earth, which requires no pre conditioning washes. Reversed-phase high-performance liquid chromatography was performed on a C18 column (70 mm x 4.6 mm I.D.) with a mobile phase of water methanol (95:5) and ultraviolet detection (268 nm). The overall recovery from plasma and urine was 91 and 94%, respectively, at the concentration of 50 ng/ml. The determination limit of the assay for 5-FU was 10 ng/ml of plasma and urine. Concentrations of 5-FU between 10 and 500 ng/ml were measured in plasma and urine with a relative standard deviation of 6.8%. In order to evaluate the procedure, plasma and urine samples from three patients treated with 5-FU by continuous intravenous perfusion, were investigated. PMID- 1452622 TI - High-performance liquid chromatographic determination of pilocarpine in plasma. AB - A high-performance liquid chromatographic procedure requiring neither derivatization nor complex sample work-up is reported for reproducibly and sensitively determining pilocarpine in plasma. Following stabilization of pilocarpine against in vitro hydrolysis using sodium fluoride, plasma samples were extracted and the extracts chromatographed on a 5-microns, low-carbon-load (6%) C18 reversed-phase column. The assay was linear between 10 and 300 ng/ml (r = 0.998). It had sufficient sensitivity to quantitate pilocarpine at concentrations as low as 10 ng/ml (signal-to-noise ratio > or = 4) using a 500 microliters sample. The assay appears to be the first published specifically for plasma determinations and has proven capable of supporting pharmacokinetics studies of pilocarpine disposition in the anesthetized dog. PMID- 1452621 TI - High-performance liquid chromatographic determination of N-methylformamide and N methyl-N-(hydroxymethyl)-formamide in human urine. AB - A reliable high-performance liquid chromatographic (HPLC) method which allows the determination in human urine of two important metabolites of N,N dimethylformamide (DMF), namely N-methylformamide (MMF) and N-methyl-N (hydroxymethyl)formamide (DMFOH), is reported. A single-step rapid purification of urine was performed on a C18 solid-phase extraction column and the eluate was injected directly on to the HPLC column. HPLC was carried out isocratically on Aminex Ion Exclusion HPX-87H column using 7.5.10(-4) M sulphuric acid as the mobile phase with ultraviolet detection at 196 nm. The method is specific, accurate, precise and sufficiently sensitive to be applied to the biological monitoring of MMF and DMFOH in workers exposed to DMF. PMID- 1452623 TI - Determination of zopiclone in plasma using column liquid chromatography with ultraviolet detection. AB - A reversed-phase liquid chromatographic method with ultraviolet detection for the determination of zopiclone in plasma is described. It is rapid, sensitive, reproducible and linear over a wide range. The method was used to study plasma zopiclone concentrations in a case of acute intoxication after oral ingestion of 300 mg of the drug. The plasma level was 1600 ng/ml 4.5 h after the dose and the elimination half-life was 3.5 h. PMID- 1452624 TI - Determination of remoxipride in human plasma and urine by reversed-phase ion-pair high-performance liquid chromatography. AB - A sensitive method is described for the measurement of remoxipride in human plasma and urine. Remoxipride and its internal standard are extracted from plasma or urine at pH 12 with a mixture of hexane and methyl tert.-butyl ether. After washing the organic phase with base, the compounds are extracted into acid and analyzed on a C18 column with ultraviolet detection at 214 nm. The mobile phase is composed of acetonitrile and aqueous buffer (sodium perchlorate and phosphoric acid, pH 1.7). The limits of reliable quantitation for remoxipride are 12.5 and 50 ng/ml for plasma and urine, respectively. The run times are 6 min for plasma and 3 min for urine. The method has been successfully used to assay remoxipride clinical study samples. This mobile phase has also been successfully applied to the analysis of other basic drugs such as cimetidine, codeine, diltiazem and quinidine with minor modifications. PMID- 1452625 TI - Evaluation of a high-performance thin-layer chromatographic technique for the determination of salbutamol serum levels in clinical trials. AB - Salbutamol concentrations were determined by high-performance thin-layer chromatography in the sera of two sets of ten volunteers at hourly intervals for 6 h after taking one 8-mg slow-release tablet. The influence of time lapse in processing of serum samples, i.e. centrifugation, extraction and chromatography, was studied. A statistical significant instability of salbutamol in the sera of patients was found which was not present in standard drug-free serum samples spiked with salbutamol and used for construction of standard curves. PMID- 1452626 TI - Determination of tetracycline antibiotics by reversed-phase high-performance liquid chromatography with fluorescence detection. AB - A highly sensitive method for the determination of tetracycline antibiotics (TCs) using reversed-phase high-performance liquid chromatography with fluorescence detection is presented. This method was based on the use of disodium ethylenediaminetetraacetate (EDTA) and calcium chloride as fluorescence increasing reagents in the mobile phase. The concentrations of each reagent in the mobile phase greatly influenced the fluorescence intensity of TCs. When the concentration of EDTA and calcium chloride were 25 and 35 mM, respectively, and the pH of the mobile phase was 6.5, the maximum fluorescence intensity was obtained. The column temperature hardly influenced the fluorescence intensity. At 3.75 ng of TCs injected, the precision (relative standard deviation) ranged from 1.12 to 2.20%. In the range 0.075-37.5 ng for tetracycline and oxytetracycline and 0.225-37.5 ng for chlortetracycline, a linear response was observed. The detection limits of this method were 49-190 pg for three different TCs. The proposed method was applied to the determination of one of the TCs in pharmaceuticals by the internal standard method using other TCs as internal standards and was also applied to determination of TCs added to fish tissue. PMID- 1452627 TI - Separation of the enantiomers of some potassium channel activators using an alpha 1-acid glycoprotein column. AB - The separations of the enantiomers of some 3,4-dihydro-2,2'-dimethyl-2H-1 benzopyrans and a related tetrahydronaphthalene on alpha 1-acid glycoprotein (Chiral-AGP) are presented, together with the results from an investigation of the effects of organic modifier and pH on the separations achieved. The general utility of Chiral-AGP in separating the enantiomers of compounds from this class of antihypertensive agents is demonstrated in this paper. PMID- 1452628 TI - Analysis of legume oligosaccharides by high-resolution gas chromatography. AB - The suitability of high-resolution gas chromatography (HGRC) for the analysis of the raffinose family oligosaccharides (raffinose, stachyose, verbascose) was investigated. Aqueous methanol (80%) extracts of pea flour were dried and derivatized with either trimethylimidazole or N-methyl-bis(trifluoroacetamide). Separation of the sugar derivatives was achieved utilizing a 10-m DB5-60W capillary column. The effects of carrier gas (He) flow-rate and split ratio on resolution and reproducibility were studied. HRGC analysis was characterized by excellent resolution and satisfactory reproducibility, and proved to be a rapid, sensitive method for quantitation of oligosaccharides in pea flours. PMID- 1452629 TI - Efficient enantioselective separation and determination of trace impurities in secondary amino acids (i.e., imino acids). AB - An R-(-)-1-(1-naphthyl)ethyl carbamoylated-beta-cyclodextrin bonded phase in conjunction with a nonaqueous polar mobile phase was used for the highly selective enantioseparation of a number of secondary amino acids after their pre column derivatization with 9-fluorenylmethyl chloroformate (FMOC). Under the conditions employed, the FMOC reagent served to "lock" the imino acid into their existing conformation thereby preventing the possibility of racemization. Furthermore, it served to increase the sensitivity to the point that trace level enantiomeric impurities were easily detected. Compared with separations that use traditional reversed-phase solvents, this method showed several advantages: higher selectivity towards the imino acid enantiomers investigated, shorter analysis times, faster equilibration of the column, more stable baseline and more sensitive fluorescence detection. The detection limits for FMOC derivatives of proline, trans-4-hydroxyproline, cis-4-hydroxyproline, pyroglutamic acid, 3,4 dehydroproline, thiaproline, penicillamine acetone adduct and pipecolic acid are in the low femtomole range. The method was used for evaluation of enantioselectivity of a number of "optically pure" commercial imino acid standards. Enantiomeric impurities as low as 0.0001% (1 ppm) can be determined in some cases. High precision determination of trace levels of D-imino acids in the presence of large amounts of corresponding (opposite) L enantiomer at 1, 0.1, 0.01% and below are demonstrated. PMID- 1452630 TI - Determination of diaminopimelic acid in biological materials using high performance liquid chromatography. AB - A method for the determination of diaminopimelic acid (DAPA) concentrations in feeds and rumen digesta by reversed-phase high-performance liquid chromatography using precolumn derivatization with o-phthaldialdehyde and fluorimetric detection was developed. Samples were oxidized and hydrolysed prior to analyses by HPLC. Hydrogen peroxide and formic acid were used for oxidation; hydrolyses were performed using 3 M hydrochloric acid under vacuum at 120 degrees C for 17 h. Oxidation allowed more space for DAPA-OPA peak elution and hydrochloric acid hydrolysis reduced sample clean-up and extended the column life. Hydrolysates were diluted, adjusted to pH 7 and filtered. A Beckman Model 507 autosampler with a precolumn derivatization cassette was used for the derivatization process and fluorimetric detection was used to measure the OPA derivatives. Samples were prepared in order to have on-column DAPA concentrations in the range 10-100 pmol. The relative recovery of the standard solutions added to the feed samples ranged from 98.4 to 102.8 %. The reproducibility of the method was evaluated by the analysis of eight alfalfa hay samples and eight alfalfa hay samples incubated in the rumen for 48 h and they yielded relative standard deviations of 2.04 % and 2.02%, respectively. PMID- 1452631 TI - Thermal desorption cold trap-injection in high-resolution gas chromatography: multivariate optimization of experimental conditions. AB - In studies of low concentrations of volatile compounds in air, the method of adsorption on porous polymers and determination by thermal desorption cold trap injection high-resolution gas chromatography is finding increasing application. Factors considered important for injection and chromatographic separation of volatile compounds by this method were investigated with the use of multivariate techniques. For the amount injected on to the chromatographic column, the factors of main importance were found to be the temperature of the injection block, the thickness of the internal coating of the cold trap and the flow-rate. Strong interaction effects were noted. For the sharpness of the chromatographic peaks, the flow-rate was the most important factor. PMID- 1452632 TI - Differential diagnosis of HTLV-I and HTLV-II infections by restriction enzyme analysis of 'nested' PCR products. AB - A 'nested' polymerase chain reaction (PCR) assay is described which is capable of detecting single copies of human T-cell lymphotropic virus (HTLV) in genomic DNA extracted from peripheral blood mononuclear cells (PBMCs). A single set of 'nested' oligonucleotide primers, based on the highly conserved tax/rex region of the viral genome, was able to detect both HTLV-I and HTLV-II proviral sequences in clinical samples of diverse geographical origins, from the United States, Great Britain, Japan, the Caribbean, Italy, Greece, Iraq and West Africa. Rapid discrimination between HTLV-I and HTLV-II infections was achieved by restriction enzyme analysis of unpurified second-round PCR products, even in those cases in which serological assays had failed to provide a definitive result. Over a 2-year period, a total of 53 HTLV infections (37 HTLV-I and 16 HTLV-II) were identified by this technique and complete concordance with serological typing, available in 41 cases, was observed. PMID- 1452633 TI - Enzyme-linked immunosorbent assay for measurement of IgG antibody to Molluscum contagiosum virus and investigation of the serological relationship of the molecular types. AB - An ELISA was developed for measuring levels of IgG antibodies to Molluscum contagiosum virus (MCV) using DNA typed purified virus as antigen. The assay was found to be specific and sensitive for antibodies to MCV as well as being economical in its use of antigen. A close relationship was found between antibody levels to the MCV molecular types 1, 1v and 2 by cross-testing sera on plates coated with the different molecular types of the virus as antigen (P < 0.001). PMID- 1452634 TI - Geographical clusters of dengue virus type 2 isolates based on analysis of infected cell RNA by the chemical cleavage at mismatch method. AB - Genetic variation in 12 strains of dengue virus type 2, isolated from several epidemic areas in different years, was studied by chemical cleavage at mismatched cytosine in DNA:RNA heteroduplexes. End-labelled cDNA probes derived from the E and NS2A genes of the New Guinea C strain were hybridized to total RNA extracted from cells infected by individual isolates. Following modification of mismatched cytosine by hydroxylamine and nucleic acid strand cleavage by piperidine, the resulting fragments of radiolabelled probe were analysed by electrophoresis and autoradiography. The patterns of bands generated corresponded to the geographical groupings of the isolates. Thus this method is suitable in epidemiological studies for rapidly surveying a large number of isolates for genetic variation in a particular gene of interest. PMID- 1452635 TI - Directed and divided attention in Alzheimer's disease: impairment in shifting of attention to global and local stimuli. AB - This study investigated the relative performance of Alzheimer's disease (AD) patients and normal controls on directed and divided attention reaction time (RT) tasks that involved the use of global-local stimuli (e.g., a large '1' made from small '2s'). Relative to normals, AD patients displayed disproportionately greater impairment on the divided attention task compared to the directed attention task. On the divided attention task, when the target remained at the same global-local level across consecutive trials, the AD patients displayed a greater facilitation effect than did the controls when responding to the second stimulus. However, when the target changed levels across consecutive trials (i.e., from the global to the local, or vice versa) the AD patients' RTs to the second stimulus were disproportionately slower than were the controls' RTs. These results demonstrated that AD patients are impaired in disengaging and shifting attention across levels of perceptual organization within the same stimulus. PMID- 1452636 TI - Neuropsychological functioning in adolescents with diabetes. AB - Investigated the relationship between disease variables, neuropsychological performance, and psychosocial status in adolescents with Insulin Dependent Diabetes Mellitus (IDDM). The study group consisted of 85 adolescents, aged 14 to 16.5 years who had been diabetic for longer than 12 months. Parameters of both recent and long-term metabolic control were determined, including diabetic incidents such as severe hypoglycemia or ketoacidosis. The mothers completed standardised measures of adolescent adjustment, and the adolescents provided self reports of psychosocial status. Neuropsychological functioning was evaluated with standardised tests of verbal and nonverbal intelligence, memory and new learning, visuo-graphic skills, mental flexibility, and problem-solving ability. Using retrospective accounts of disease history, there was no relationship between neuropsychological functioning and variables such as age of onset, chronic poor control, or major metabolic crises. The findings emphasise the need for a long term, prospective study of a cohort of diabetic children from the time of diagnosis to clarify causal relationships, if any, between illness variables, neuropsychological performance, and psychosocial factors. PMID- 1452637 TI - Cognitive rehabilitation of the hemineglect disorder in chronic patients with unilateral right brain damage. AB - Thirteen patients with a stabilized hemineglect symptomatology due to right hemisphere lesions were subjected to a rehabilitation training specifically aimed at reducing the scanning deficit. The training consisted of four procedures (visual-spatial scanning, reading and copying training, copying of line drawings on a dot matrix, and figure description) which lasted 40 sessions. By the end of therapy, the patients as a group showed significant improvements on several standard tests of hemineglect. The results on a Semi-structured Scale for the Functional Evaluation of Hemineglect pointed to the extension of exploratory improvements to situations similar to those of daily life. In contrast, patients improved very slightly on a variety of standard visual-spatial tests, indicating the specificity of training in reducing the scanning defect. Seven patients were examined at a follow-up several months after the end of therapy and appeared stable on both standard and functional tests of neglect. PMID- 1452638 TI - Cognitive dysfunction after aneurysm of the anterior communicating artery. AB - The present study examined the nature of the amnestic syndrome following aneurysm of the anterior communicating artery (ACoA) in humans. Eleven ACoA and 13 subjects with intracranial hemorrhages (ICH) elsewhere in the brain were administered a battery of standard neuropsychological tests. The ACoA group performed significantly worse than the ICH controls on tests of delayed verbal memory and on the Wisconsin Card Sorting Test, despite significantly higher Full Scale IQ. No significant differences were observed between groups on tests of immediate recall, attention and concentration, and visuo-spatial functions, although the ACoA group tended to perform better on many of these tests. The results do not support the hypothesis that the cognitive impairments observed following ACoA aneurysm are the result of diffuse cortical damage. The role of specific anterior cerebral structures in defining the "ACOA syndrome" are discussed. PMID- 1452639 TI - Factorial structure of the Waterloo Handedness Questionnaire for control and learning-disabled adults. AB - This study examined the factorial structure of the 32-item version of the Waterloo Handedness Questionnaire (Steenhuis & Bryden, 1989) with a sample of control (n = 325) and learning-disabled (LD) (n = 147) subjects. On the basis of Principal Components Analyses, we have replicated the work of Steenhuis and Bryden (1989) who suggested that hand preference factors for control subjects are multifactorial in nature and are related more to "skilled" and "less skilled" activities rather than on distal/proximal musculature. Further, we have found that the factor structure for hand preference in LD adults is somewhat different than of normally achieving adults. The primary difference occurred within Factor 2. Unlike control subjects, whose Factor 2 items were classified as "less skilled" and preference was less lateralized, items loading on this factor for LD subjects were classified as "skilled" and showed strongly lateralized responses for both left and right handers. Presumably, LD adults show a less marked distinction between "skilled" and "less skilled" unimanual motor activities than control subjects suggesting different degrees of manual laterality between the groups. PMID- 1452640 TI - Evidence of presymptomatic cognitive decline in Huntington's disease. AB - Asymptomatic persons at risk for Huntington's disease (HD) (N = 28) were assessed with neuropsychological, psychiatric, and neurologic tests while undergoing genetic linkage studies to determine their probability of carrying the HD gene. Those participants who were subsequently identified as probable gene carriers did not differ on neurologic or psychiatric examination from those subsequently identified as probable noncarriers. Neuropsychological data are presented for a subset of participants free of other conditions (such as alcoholism) putting them at risk for cognitive deficits. Among these subjects, probable gene carriers were inferior to probable noncarriers on the neuropsychological battery as a whole and on several individual tests involving learning and memory. The results suggest the presence of cognitive decline prior to identifiable motor impairments in HD. PMID- 1452641 TI - Peer review for manuscript and grant submissions: relevance for research in clinical neuropsychology. PMID- 1452642 TI - Adjusting for demographic covariates by the analysis of covariance. PMID- 1452643 TI - Multicenter evaluation of the AntigEnz Chlamydia enzyme immunoassay for diagnosis of Chlamydia trachomatis genital infection. AB - To evaluate the AntigEnz Chlamydia enzyme immunoassay (EIA) (Baxter/Bartels, Issaquah, Wash.), we studied 320 men and 1,209 women attending clinics for sexually transmitted diseases in Baltimore, San Francisco, and Seattle. At examination, two separate swabs were obtained from each patient, one for chlamydial culture and one for EIA. Cervical samples were collected from women, and urethral samples were collected from men. The prevalence of chlamydial infection by culture was 9% in Baltimore (n = 532), 11% in Seattle (n = 500), and 9% in San Francisco (n = 497). To resolve specimens with discrepant culture and EIA results, the EIA transport buffer was centrifuged and the resuspended pellet was stained by direct immunofluorescence to determine whether elementary bodies were present. Overall sensitivity of the AntigEnz Chlamydia assay compared with culture was 87% in men and 86% in women, and overall specificities were 94 and 97%, respectively. Differences between centers were seen, with sensitivities ranging from 76% among men and 79% among women in Seattle to 100% among men and 95% among women in Baltimore. With a true positive considered to be either a culture-positive or an EIA- and direct immunofluorescence-positive specimen, the revised sensitivity was 91% in men and 88% in women. Overall revised specificity was 99% in both men and women. We conclude that in this high-prevalence population, the sensitivity and specificity of this assay compare favorably with those of other noncultural antigen detection tests for the diagnosis of chlamydial genital infection. PMID- 1452644 TI - Seroprevalence of immunoglobulin M (IgM) and IgG antibodies to polysaccharides of Streptococcus pneumoniae in different age groups of Ecuadorian and German children. AB - The age-specific prevalence of serum immunoglobulin M (IgM) antibody to capsular polysaccharides of Streptococcus pneumoniae, as detected by enzyme-linked immunosorbent assay, was studied in 1,301 Ecuadorian children enrolled in a national nutrition and health survey. This prevalence was 6% in infants < 6 months old and increased to 28% in children 6 to 11 months old, 49% in those 12 to 17 months old, and 58% in those 18 to 23 months old. About 80% of the 5-year old children had this antibody. When tested separately against six different capsular polysaccharides, serum IgM antibody reacted with decreasing frequency with serotype 3, 8, 19, 6, 23, and 1 capsular polysaccharides. We did not observe a broadening of the antibody response with increasing age in the sense that more and more serotypes were recognized. A similar age-related prevalence was found for IgM antibody to the species-specific C-polysaccharide of S. pneumoniae and for IgG antibody to capsular polysaccharides of S. pneumoniae. A smaller German serum collection showed a comparable age-related prevalence of pneumococcus specific serum IgG and IgM antibodies. The highest incidence of respiratory diseases was observed in 1- and 2-year-old Ecuadorian children. It thus seems that acquisition of serum antibody to S. pneumoniae reflects more the developmental maturation of an immune response than an actual exposure to different pneumococcal serotypes. PMID- 1452646 TI - Whole-cell protein electrophoresis for typing Mycobacterium tuberculosis. AB - A method of discriminating between strains of Mycobacterium tuberculosis by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell proteins combined with a sensitive silver stain is described. Thirty-five isolates of M. tuberculosis and five isolates from other species of Mycobacterium were examined, including serial isolates from the same patients and isolates from a small cluster of hospital cases. Different species of Mycobacterium were clearly distinguished, and within the species M. tuberculosis, different fingerprints were obtained, allowing discrimination of some strains from different patients. The reproducibility and discrimination of the technique are discussed. PMID- 1452645 TI - Detection of specific antibodies in gingival crevicular transudate by enzyme linked immunosorbent assay for diagnosis of human immunodeficiency virus type 1 infection. AB - The purpose of this open and multicenter trial was to determine the usefulness of antibody detection by enzyme-linked immunosorbent assay (ELISA) in gingival crevicular transudate (GCT), which was collected with an investigational device (Orasure; Epitope, Beaverton, Oreg.), for the diagnosis of human immunodeficiency virus type 1 (HIV-1) infection and to compare it with antibody detection in serum. A total of 1,880 individuals were tested, as follows: 354 HIV-1-infected individuals (111 asymptomatics individuals and 243 individuals with AIDS), 46 individuals with autoimmune diseases (AD), 296 individuals with dental diseases, 42 individuals with other chronic diseases, and 1,142 healthy individuals. Sera from 356 individuals and GCT from 354 individuals were positive for HIV-1 antibodies. There were two false-negative gingival samples, one from an HIV-1 positive asymptomatic individual and one from a patient with AIDS. HIV-1 antibodies were unexpectedly detected in both serum and GCT of two individuals, one with dental disease and one with pulmonary tuberculosis. None of the sera or GCTs from healthy subjects or patients with AD were positive. Compared with the serum assay, the sensitivity, specificity, and positive and negative predictive values of the GCT assay were 99.5, 100, 100, and 99.9%, respectively. Of 355 paired serum-GCT samples that were HIV-1 positive by ELISA and that were tested by Western blot (immunoblot), all were positive for HIV-1 by using the U.S. Public Health Service interpretation criteria, while among gingival samples, 301 were positive, 52 were indeterminate, and 2 were negative. Of 82 negative paired samples selected at random, 80 were negative by Western blotting of serum and GCT and 2 were indeterminate by Western blotting of serum and negative by Western blotting of GCT (a healthy blood donor and a patient with dermatopolymyositis). Testing for HIV-1 antibodies in GCT is a simple and reliable screening procedure in populations with high and low prevalences of infection because of the high sensitivity and specificity of the method, and it offers improved safety for hospital personnel. PMID- 1452648 TI - Evaluation of three immunoassays for detection of Chlamydia trachomatis in urine specimens from asymptomatic males. AB - The performances of three commercially available immunoassays (Chlamydiazyme/Antibody Blocking Assay [Abbott Diagnostics, Abbott Park, Ill.], IDEIA [Analytab Products, Plainview, N.Y.], and Microtrak EIA [Syva Co. Palo Alto, Calif.]) were evaluated for the detection of Chlamydia trachomatis in urine specimens from asymptomatic males. Assay results were compared with direct specimen immunofluorescence (DFA) analysis of urine sediment (Syva Microtrak; Syva Co.), which was chosen as the study confirmation assay. An overall Chlamydia prevalence of 7% (24 of 340) was found in our study population, with peak incidences occurring in the adolescent (8 of 93 specimens) and young adult (11 of 146 specimens) age groups. Sensitivity and specificity data among the Chlamydiazyme, IDEIA, and Microtrak enzyme immunoassays (EIAs) were determined to be 79.1 and 99%, 91.7 and 98%, and 95.8 and 99%, respectively. The Microtrak EIA and IDEIA products demonstrated sensitivities and specificities equal to or greater than those claimed for urine specimens. The diagnostic accuracies of these assays on asymptomatic subjects, along with the ease of this collection method, suggest a role for these products as screening tools. The sensitivity of the Chlamydiazyme assay was lower than that claimed previously in symptomatic patients, with 5 of 24 positive specimens demonstrating false-negative results. In those cases, centrifugation of the original immunoassay aliquot material and then DFA examination confirmed specimen positivity. Urine immunoassay screening in combination with DFA confirmation (which was chosen because it has antibody epitopic specificity different from that of the primary assay) provides a high degree of diagnostic precision. The use of noninvasive collection methods could result in greater testing compliance among asymptomatic males and, subsequently, could reduce the incidences of both symptomatic and silent chlamydial infections. PMID- 1452647 TI - Use of a recombinant 170-kilodalton surface antigen of Entamoeba histolytica for serodiagnosis of amebiasis and identification of immunodominant domains of the native molecule. AB - We expressed the gene that encodes one of the major surface antigens of Entamoeba histolytica, the 170-kDa protein (1,270 amino acids), as a glutathione S transferase fusion protein containing amino acids 1 to 1202 (lacking the putative transmembrane and cytoplasmic regions) and as separate fusion proteins containing each of three major domains of the 170-kDa molecule. Lysates from bacteria induced to express one of these proteins were used as the target antigens in a Western blot (immunoblot) analysis to determine whether a recombinant 170-kDa antigen could serve as the basis for a serologic test used to detect invasive amebiasis and whether there are differences in humoral immunogenicity among the three major domains of the 170-kDa antigen. Among patients with invasive amebiasis from three major areas where the disease is endemic and two sites in the United States, 54 (90%) of 60 had antibodies to the recombinant 170-kDa protein. Among 37 patients from regions where the disease is endemic and 20 patients from the United States without amebic disease, 1 (2%) of 57 had antibodies to the recombinant 170-kDa protein. We found significant differences in seroreactivity to each of three major domains of the molecule among patients seropositive for the complete construct, ranging from 100% seroreactivity with the fusion protein containing the domain designated cysteine rich and 89% seropositivity with the fusion protein incorporating a portion of the region designated cysteine poor to only 9% seropositivity for the fusion protein containing the pseudorepeat domain. Our study indicates that a serologic test based on the recombinant 170-kDA antigen could serve as a highly sensitive and specific test for acute invasive amebiasis. PMID- 1452649 TI - Scedosporium inflatum osteomyelitis in a dog. AB - Scedosporium inflatum Malloch et Salkin was found to cause osteomyelitis in a 6 year-old spayed female beagle. The previously healthy dog suddenly developed right-forelimb lameness. Bony changes consisting of proliferation with some lysis were noted on radiographic examinations. Microscopic observations of stained sections of tissue obtained by biopsy of the distal humerus revealed the presence of septate branching hyphae. Cultures inoculated with tissue from a later biopsy yielded a mold subsequently identified as S. inflatum. Tissue sections stained with specific Scedosporium fluorescent-antibody conjugate were positive, further substantiating the diagnosis. Although the dog was treated with oral itraconazole, no improvement in the animal's condition was noted, and it was euthanized. Autopsy revealed dissemination of the etiologic agent to the lungs. PMID- 1452650 TI - Detection of Shigella dysenteriae type 1 and Shigella flexneri in feces by immunomagnetic isolation and polymerase chain reaction. AB - A combination of immunomagnetic separation (IMS) and a polymerase chain reaction (PCR) procedure was used for direct isolation and identification of Shigella dysenteriae type 1 and Shigella flexneri from feces. Immunomagnetic particles were coated with monoclonal antibody MASFB, which is specific for a common epitope of the O polysaccharides of S. dysenteriae type 1 and S. flexneri. Bacteria bound to the beads were boiled in water, and target DNA was amplified with a primer pair specific for a gene coded on the invasion-associated locus (ial) of the large virulence plasmid of all four Shigella spp. and enteroinvasive strains of Escherichia coli. A 320-bp DNA fragment was generated and detected by an alkaline phosphatase-conjugated probe. Nonviable cells were also captured and detected by this technique. The method is simple and fast (7 h) and has a detection limit of ca. 10 Shigella organisms per g in fecal samples. The combined IMS-PCR assay correctly identified all 57 samples carrying S. dysenteriae type 1 and 68 samples carrying S. flexneri from 238 fecal specimens and also permitted detection of 17 samples carrying Shigella spp. from 113 specimens from diarrheal patients in whom shigellae were not detected by conventional culture. PMID- 1452651 TI - A monoclonal antibody for distinction of invasive and noninvasive clinical isolates of Entamoeba histolytica. AB - Approximately 10% of the world population is infected with Entamoeba histolytica, but only 10% of the carriers develop symptomatic amebiasis. This discrepancy could be explained by the genotypic differences between the morphologically indistinguishable invasive and noninvasive strains of E. histolytica currently identified by zymodeme analysis, a technique that is unsuitable for routine diagnostic laboratories. Here we report the production of a monoclonal antibody against E. histolytica and its use in an immunofluorescence assay to identify invasive isolates cultured from stool samples of infected patients in several regions where amebiasis is endemic: Bangladesh, Colombia, and Mexico. After testing a total of 88 E. histolytica isolates, the correlation between zymodeme characterization and the immunofluorescence assay with the invasive isolate specific monoclonal antibody was 100%. The epitope detected by the invasive isolate-specific monoclonal antibody resides in a previously undescribed internal protein with molecular masses of 84 and 81 kDa in axenic and polyxenic E. histolytica strains, respectively. PMID- 1452652 TI - Identification of meningococcal serosubtypes by polymerase chain reaction. AB - The polymerase chain reaction was used as the basis of a novel typing method for Neisseria meningitidis. Southern hybridization experiments demonstrated that it was possible to identify genes encoding different serological variants of the meningococcal class 1 outer membrane protein by probing with polymerase chain reaction products corresponding to known epitopes. A set of 14 defined variable regions was prepared in bacteriophage M13mp19 by the cloning of polymerase chain reaction products. The phage were dot blotted onto membrane filters, which were used as targets for hybridization of radiolabeled amplified class 1 outer membrane protein genes. Thus, the presence of many different subtype-specific epitopes could be investigated in one experiment. This technique was evaluated with a set of serological reference strains, mainly of serogroup B organisms, and provided an alternative, rapid, and comprehensive typing system that was capable of distinguishing known serosubtypes and also of defining currently untypeable strains independently of sodium dodecyl sulfate-polyacrylamide gel electrophoresis or serological analysis. An additional advantage of this technique was that in the case of an unknown serosubtype (i.e., one that did not hybridize with any of the known samples), the DNA amplified from the original sample could be used to determine the nucleotide sequence of the novel serosubtype and to clone the corresponding variable region into bacteriophage M13. It may be possible to develop this procedure for the diagnostic detection and typing of meningococci directly from clinical samples even when culture is not possible because of antibiotic treatment of an acute case. PMID- 1452653 TI - Epidemiology of Tsutsugamushi disease in relation to the serotypes of Rickettsia tsutsugamushi isolated from patients, field mice, and unfed chiggers on the eastern slope of Mount Fuji, Shizuoka Prefecture, Japan. AB - A total of 59 strains of Rickettsia tsutsugamushi were isolated from patients (24 isolates), Apodemus speciosus mice (30 isolates), and unfed larvae of Leptotrombidium scutellare (2 isolates) and Leptotrombidium pallidum (3 isolates) in the Gotenba-Oyama District, Shizuoka Prefecture, Japan. All these isolates were classified into the three serotypes Karp, Kawasaki, and Kuroki based on reactivity with strain-specific monoclonal antibodies. Kawasaki- and Karp-type rickettsiae were isolated from L. scutellare and L. pallidum, respectively, and the geographic distribution of patients and rodents infected with these two types of rickettsiae coincided with the areas densely populated by the respective chiggers. From these results, we conclude that Kawasaki-type rickettsiae are transmitted by L. scutellare and Karp-type ones are transmitted by L. pallidum. Kawasaki-type rickettsial infections were prevalent in early autumn, and Karp type infections showed a peak of occurrence in the late autumn, reflecting the seasonal fluctuations of L. scutellare and L. pallidum. Isolates of Kuroki-type rickettsiae were obtained only from four patients in October and November, and the relationship between this type of rickettsia and its vector species could not be fully defined. PMID- 1452654 TI - Detection of Chlamydia trachomatis in endocervical specimens by polymerase chain reaction. AB - A rapid and sensitive polymerase chain reaction (PCR)-based assay for detection of Chlamydia trachomatis in cervical specimens is described. This assay consists of (i) sample preparation which avoids the use of heat, centrifugation, or organic extractions; (ii) rapid, two-temperature PCR amplification of C. trachomatis cryptic plasmid sequences; and (iii) capture and colorimetric detection of amplified DNA in microwell plates. PCR was compared with culture by using 503 cervical specimens. After resolution of discrepant specimens with a confirmatory PCR assay directed against the chlamydial major outer membrane protein gene, PCR had a sensitivity of 97% and a specificity of 99.7% while culture had a sensitivity of 85.7% and a specificity of 100%. In a separate study, PCR was compared with a direct specimen enzyme immunoassay (Chlamydiazyme; Abbott Diagnostics) by using 375 cervical specimens. After resolution of discrepant specimens, PCR had a sensitivity and specificity of 100%, while the enzyme immunoassay had a sensitivity of 58.8% and a specificity of 100%. PMID- 1452655 TI - Polymerase chain reaction-based detection of Trypanosoma cruzi DNA in serum. AB - DNAs prepared from chagasic patients' sera were amplified by the polymerase chain reaction using oligonucleotide primers which anneal specifically to a highly repetitive sequence of Trypanosoma cruzi nuclear DNA. Samples from both acutely and chronically infected patients yielded positive results by this method. No significant difference was observed when either whole blood or serum samples of the patients were used. These results indicate that serum instead of whole-blood samples could be used for polymerase chain reaction-based detection of T. cruzi in field studies without the need of applying any special chemical treatment to the specimens. This would represent a considerable advantage due to the easier handling and transportation of serum as compared with whole-blood samples, especially in tropical climates. PMID- 1452656 TI - Improved stool concentration procedure for detection of Cryptosporidium oocysts in fecal specimens. AB - Epidemiologic and laboratory data suggest that coprodiagnostic methods may fail to detect Cryptosporidium oocysts in stool specimens of infected patients. To improve the efficacy of stool concentration procedures, we modified different steps of the Formalin-ethyl acetate (FEA) stool concentration technique and evaluated these modifications by examining stool samples seeded with known numbers of Cryptosporidium oocysts. Because these modifications failed to improve oocyst detection, we developed a new stool concentration technique that includes FEA sedimentation followed by layering and flotation over hypertonic sodium chloride solution to separate parasites from stool debris. Compared with the standard FEA procedure, this technique improved Cryptosporidium oocyst detection. The sensitivities of the two concentration techniques were similar for diarrheal (watery) stool specimens (100% of watery stool specimens seeded with 5,000 oocysts per g of stool were identified as positive by the new technique, compared with 90% of stools processed by the standard FEA technique). However, the most significant improvement in diagnosis occurred with formed stool specimens that were not fatty; 70 to 90% of formed stool specimens seeded with 5,000 oocysts were identified as positive by the new technique, compared with 0% of specimens processed by the standard FEA technique. One hundred percent of formed specimens seeded with 10,000 oocysts were correctly diagnosed by using the new technique, while 0 to 60% of specimens processed by the standard FEA technique were found positive. Similarly, only 50 to 90% of stool specimens seeded with 50,000 oocysts were identified as positive by using the standard FEA technique, compared with a 100% positive rate by the new technique. The new stool concentration procedure provides enhanced detection of Cryptosporidium oocysts in all stool samples. PMID- 1452657 TI - Baculovirus expression of the nucleoprotein gene of measles virus and utility of the recombinant protein in diagnostic enzyme immunoassays. AB - A recombinant baculovirus that expresses the nucleoprotein gene of measles virus (Edmonston vaccine strain) under the transcriptional control of the polyhedrin promoter was generated. The expressed protein (B-MVN) comigrated with the authentic viral nucleoprotein as observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and it was phosphorylated. The B-MVN protein proved to be reactive with monoclonal antibodies in radioimmunoprecipitations, and it was immunogenic, eliciting in mice antisera that recognized the native nucleoprotein. In addition, the B-MVN protein was evaluated as a replacement source of antigen for whole virus in enzyme immunoassays (EIAs) for detection of measles virus-specific immunoglobulin M (IgM) and IgG antibodies. A capture IgM EIA with the B-MVN protein as antigen detected specific IgM antibodies in 18 (72%) acute- and all convalescent-phase specimens from 25 clinical measles cases and exceeded 99% specificity with 120 control specimens. An indirect IgG EIA with the B-MVN protein detected specific IgG antibodies in 129 of 131 (98%) serum specimens with antibodies to measles virus, and results obtained from testing 268 additional serum specimens were better correlated with measles virus-neutralizing antibodies than those obtained with a commercial EIA. PMID- 1452658 TI - Susceptibility testing of Cryptococcus neoformans: a microdilution technique. AB - We studied a series of test conditions in a microtiter system to define the optimal method for determining the susceptibility of Cryptococcus neoformans to antifungal agents. Twenty-one isolates of C. neoformans were grown for 24 or 48 h in four chemically defined media: yeast nitrogen base (BYNB 7); RPMI 1640; synthetic amino acid medium--fungal (SAAMF), buffered at pH 7.0 to select the medium that best supported growth of this fastidious yeast; and yeast nitrogen base, pH 5.4 (YNB 5.4). Maximum growth of C. neoformans, at 35 degrees C, was obtained in YNB 5.4, with the next highest growth levels in BYNB 7, SAAMF, and RPMI. Growth at 24 h was uniformly poor in all media and lacked reproducibility. In contrast, incubation for 48 h gave adequate growth with low standard deviations, and 48 h was selected as the optimal incubation period for this study. Comparison of the relationship between growth kinetics and initial inoculum size for eight cryptococcal isolates showed that 10(4) cells per ml yielded optimal growth in BYNB 7 and YNB 5.4, whereas 10(5) cells per ml was optimal in RPMI and SAAMF. Furthermore, variation of inocula from 10(3) to 10(5) cells per ml showed small but significant inoculum effects in determining MICs of fluconazole, amphotericin B, and flucytosine for C. neoformans. Therefore, 10(4) cells per ml was chosen as the optimal inoculum for susceptibility testing in this study. Mean MICs of fluconazole, amphotericin B, and flucytosine for 21 crytococcal isolates in RPMI and BYNB 7 were low (for example, fluconazole had mean MICs of 1.2 and 1.3 micrograms/ml in RPMI and BYNB 7, respectively) and differed significantly from medium to medium. In contrast, the MICs obtained in SAAMF were significantly higher (e.g., fluconazole had a mean MIC of 2.2 micrograms/ml). Variance in MICs was large with fluconazole and flucytosine but small with amphotericin B, irrespective of the medium used. A microtiter system employing BYNB 7 as the medium, 48 h as the incubation period, and 10(4) cells per ml as the final inoculum is a simple, accurate, and reproducible method for the testing of C. neoformans susceptibility to fluconazole, amphotericin B, and flucytosine. PMID- 1452659 TI - A novel polymerase chain reaction method for detection of human immunodeficiency virus in dried blood spots on filter paper. AB - A method for detection of proviral human immunodeficiency virus DNA in dried blood spots on filter paper by direct polymerase chain reaction (PCR) has been developed. To develop the method, a standard system was used which was prepared from cells each containing a single integrated provirus and titrated with normal donor blood. This rapid procedure provides virtually quantitative yields of nuclear DNA and exploits most of the standard methodology described for blood specimens. A nested PCR using SK38-SK39 gag as the internal primer pair was also designed; this PCR detected a single copy of provirus per filter at near theoretical frequency with SK19 probe. The utility of the procedure was demonstrated with clinical specimens. Blood spot filters from human immunodeficiency virus-infected and uninfected individuals were readily and unequivocally discriminated. The method is designed for ultimate use with large (1.5-ml) sample preparation tubes that are compatible as PCR tubes with thermal cyclers. This will permit convenient, direct single-tube PCR of dried blood specimens on filters. It should be adaptable to analysis of dried blood spots for a variety of infectious or genetic diseases. PMID- 1452660 TI - Characterization and comparison of Australian human spotted fever group rickettsiae. AB - The microbiological and molecular characteristics of the rickettsiae isolated from humans with Queensland tick typhus (QTT) caused by Rickettsia australis and the recently described Flinders Island spotted fever (FISF) were compared. Clinically and serologically, the diseases are similar. Cell culture reveals differences in the plaque-forming abilities of the isolates. Characterization of the gene encoding the genus-specific 17-kDa antigen of R. australis revealed a unique nucleotide sequence unlike those of the FISF isolate and Rickettsia rickettsii. Southern blot analysis of rickettsial DNA from the isolates with a 17 kDa-antigen gene probe revealed the presence of this gene in all isolates but no difference in banding patterns. When a probe for the rRNA genes was used, clear differences in banding patterns of isolates from patients with QTT and FISF were revealed. Thus, the rickettsiae isolated from patients with FISF differ from those from patients with QTT and may represent a new rickettsial species. PMID- 1452661 TI - Evaluation of the autoSCAN-W/A rapid system for identification and susceptibility testing of gram-negative fermentative bacilli. AB - The autoSCAN-Walk-Away (W/A) system for identification and susceptibility testing was evaluated for 400 gram-negative fermentative bacteria by using the API 20E (366 isolates) and/or tube biochemical tests as the reference identification system and a frozen microdilution MIC tray system for susceptibility testing. The W/A system performed well for identification of this group of organisms representing 14 genera and 30 species, showing a sensitivity of 96% and results available in 2 h. Of the 16 misidentifications, 6 were with Serratia liquefaciens. A total of 63 isolates (17%) required further tests to complete the identification, compared with 106 (29%) of the isolates which required additional tests for the API 20E identification. Approximately half (32) of the additional tests with the W/A system were required in order to separate Citrobacter diversus from C. amalonaticus. For susceptibility determinations, the W/A system demonstrated an overall agreement of 93% (4,102 determinations) with 40 major errors (0.98%). However, of the 906 resistant organism-drug combinations in the study, there were 115 very major errors, for a false-susceptibility rate of 12.7% of the resistance determinations. Among these very major errors, 80% occurred with piperacillin and the cephalosporins. The W/A system completed the MIC determinations in 7 h; however, the difficulty in detecting resistance with some antimicrobial agents limited the advantages of the rapid susceptibility testing. PMID- 1452662 TI - Establishment of a particle-counting method for purified elementary bodies of chlamydiae and evaluation of sensitivities of the IDEIA Chlamydia kit and DNA probe by using the purified elementary bodies. AB - To evaluate the sensitivity of commercially available test kits for detection of chlamydiae, we established a method of purifying Chlamydia trachomatis and Chlamydia pneumoniae elementary bodies (EBs). We then subjected the purified EBs, together with the purified EBs of Chlamydia psittaci, to the IDEIA Chlamydia (IDEIA) and DNA probe test kits to determine the EB numbers at the detection limits. The sensitivities of the test kits were thus compared. The results can be summarized as follows. (i) Intact EBs in the purified preparations were present at 100, 96.3, and 97% for the C. psittaci Cal 10, C. trachomatis L2/434/Bu (L2), and C. pneumoniae TW-183 strains, respectively. The preparations of the L2 and TW 183 EBs contained a few EB envelopes, which reacted with antilipopolysaccharide monoclonal antibodies, as did the intact EBs, indicating that elimination of EB envelopes is not required for testing of the IDEIA kit's sensitivity. (ii) We established a method of counting intact EBs and EB envelopes under a scanning electron microscope after sedimentation of EBs on a coverslip by centrifugation. (iii) The EB numbers per assay at the cutoff level, which is set up in the IDEIA kit, were 9.6 x 10(2), 6.5 x 10(3), and 2.5 x 10(4) for the L2, TW-183, and Cal 10 strains, respectively. When the same EB preparations were applied to the DNA probe kit, the EB number at the cutoff level was 7.5 x 10(3) per assay for the L2 strain, but no reaction occurred for the Cal 10 and TW-183 strains at any EB number, indicating that the DNA probe kit is highly specific for C. trachomatis. Although the IDEIA kit designed for detection of C. trachomatis showed a sensitivity superior to that of the DNA probe, the chlamydial species was not determined by the IDEIA kit. PMID- 1452664 TI - Comparison of two culture approaches, blind passage and dual observation, for detecting Chlamydia trachomatis in various prevalence populations. AB - Chlamydia trachomatis diagnosis in our laboratory consisted of dual inoculation of shell vials and detection of inclusions by using fluorescein-conjugated monoclonal antiserum; the second culture vial was conventionally used for blind passage when the first vial was negative. We compared the increase in positivity using blind passage with that of a strategy utilizing observation of two stained monolayers (dual observation) without blind passage, in an effort to reduce the reporting time and labor associated with the conventional approach. A total of 4,329 specimens were obtained from an obstetrics and gynecology (OB-GYN) clinic (2,563 specimens) and the sexually transmitted disease clinic (1,766 specimens). These specimens were used to compare the two strategies. Blind passage of 1,269 initially culture-negative specimens from the OB-GYN clinic resulted in an additional 6 positive chlamydial diagnoses. In comparison, a similar number of specimens (1,294) from the OB-GYN clinic collected subsequently to the first group were tested by dual observation. There were five additional positive findings. A similar evaluation of specimens from the sexually transmitted disease clinic was performed. Blind passage of 313 initially culture-negative specimens yielded 3 additional positive diagnoses, whereas dual observation of 1,435 similar specimens resulted in 9 positive diagnoses. On the basis of analysis of 4,332 specimens, sensitivity of dual observation is comparable to that of blind passage; labor, cost, and reporting time of dual observation are reduced in comparison to those of blind passage. PMID- 1452663 TI - Analysis of relationships among isolates of Citrobacter diversus by using DNA fingerprints generated by repetitive sequence-based primers in the polymerase chain reaction. AB - Oligonucleotide probes which match consensus sequences of the repetitive extragenic palindromic (REP) element hybridize to genomic DNA of diverse bacterial species. Primers based on the REP sequence generate complex band patterns with genomic DNA in the polymerase chain reaction (PCR), a technique named REP-PCR. We used REP-PCR with genomic DNA to fingerprint 47 isolates of Citrobacter diversus. Previously, 37 were assigned electrophoretic types (ETs) by multilocus enzyme electrophoresis and 35 were evaluated by using outer membrane protein profiles. Fingerprints were compared by visual inspection and by similarity coefficients (SimCs) based on the number of common bands versus total bands between two given isolates. DNA fingerprints were highly similar visually for patient pairs and outbreak-related sets. SimCs for these were > or = 0.952. Fingerprints of isolates with different ETs generally were distinctive. Among 21 unrelated isolates representing 15 ETs, only 6 of 210 comparisons had SimCs of > or = 0.952. REP-PCR rapidly generated DNA fingerprints which were highly similar for epidemiologically linked isolates of C. diversus and distinct for previously characterized strains within this species. The ability of this method to discriminate between C. diversus isolates with the same biotype was similar to that of multilocus enzyme electrophoresis and outer membrane protein profiles. REP-PCR may be useful in evaluation of apparent outbreaks of this or other bacterial species which possess these extragenic, repetitive elements. PMID- 1452665 TI - Urinary tract infection due to Rahnella aquatilis in a renal transplant patient. AB - Rahnella aquatilis is an unusual gram-negative rod belonging to the family Enterobacteriaceae. It inhabits fresh water and is rarely isolated from clinical specimens. We report the case of a urinary tract infection caused by this organism in a renal transplant patient. PMID- 1452666 TI - DNA probe for strain typing of Cryptococcus neoformans. AB - A 7-kb linear plasmid, harbored by a URA5 transformant, hybridized to all the chromosomes of Cryptococcus neoformans separated by contour-clamped homogeneous electric field electrophoresis. Its linear maintenance was determined to have been facilitated by the presence of telomere-like sequences at its free ends. Hybridization of this plasmid to AccI-digested genomic DNAs of 26 C. neoformans strains generated 21 unique DNA fingerprints. The DNA fingerprints of isolates within the same serotype were more similar to one another than to those from different serotypes. An acapsular clinical isolate, strain 602, widely used in immunological studies and previously thought to be in serotype D, showed DNA fingerprints typical of serotype A isolates. Isogenic strains of C. neoformans exhibited DNA fingerprints that were identical to one another. The DNA fingerprints were stable and reproducible in spite of repeated transfers in the laboratory on either complex (1% yeast extract, 2% Bacto Peptone, 2% glucose) or minimal (yeast nitrogen base) medium. The DNA fingerprints of isolates recovered from primary blood and cerebrospinal fluid cultures of patients for whom AIDS had been diagnosed showed that the original infection in each of these patients contained a homogeneous population of C. neoformans. The DNA fingerprints of isolates recovered from different tissues of infected mice and from patients undergoing different drug therapy regimens were also found to be very stable. PMID- 1452667 TI - Comparative study of antipneumocystis agents in rats by using a Pneumocystis carinii-specific DNA probe to quantitate infection. AB - A repetitive genomic DNA clone (B12-2) that specifically hybridizes to Pneumocystis carinii DNA has been identified. No cross-hybridization to genomic DNA prepared from bacteria, other fungi, protozoa, or mammals was observed. Clone B12-2 is multiply represented in the P. carinii genome. By direct hybridization to DNA prepared from the lungs of immunosuppressed rats, the probe can detect the equivalent of fewer than 1,000 P. carinii organisms. A hybridization assay employing clone B12-2 has been developed to quantitate organism load in the rat model for P. carinii. Application of the assay to track the accumulation of organisms during the immunosuppression regimen as well as to monitor the efficacy of two drug therapies used clinically for the treatment of P. carinii pneumonia is described here. The clone B12-2 hybridization assay for the determination of P. carinii organism load possesses several advantageous features and thus should serve to complement conventional staining and immunohistochemical methods. PMID- 1452668 TI - Colonization of the female genital tract with Staphylococcus saprophyticus. AB - The prevalence of colonization by Staphylococcus saprophyticus of the urogenital tracts of 276 women from an outpatient gynecology practice was determined by using selective and enrichment culture techniques. Nineteen subjects (6.9%) were found to be colonized by S. saprophyticus. The rectum was the most frequent site of colonization and was responsible for 40% of the isolates; this was followed in decreasing order by the urethra, urine, and cervix. Women colonized by S. saprophyticus were more likely to have experienced a urinary tract infection in the previous 12 months (P = 0.058; odds ratio, 2.844; 95% confidence interval, 1.054 to 7.671). Patients colonized by S. saprophyticus tended to have had their menstrual periods more recently (P = 0.066), experienced sexual intercourse more recently (P = 0.168), and had a recent or concurrent diagnosis of vaginal candidiasis (P = 0.111; odds ratio, 2.393; 95% confidence interval, 0.877 to 6.528). A seasonal variation in colonization was observed, with colonization most likely occurring during the summer and fall. Follow-up for an average of 6.75 months failed to document any colonized woman progressing to symptomatic urinary tract infection. In addition, 21 women colonized by non-S. saprophyticus, novobiocin-resistant, coagulase-negative staphylococci were identified and characterized. PMID- 1452669 TI - Immunoblot analysis of the humoral immune response to Pythium insidiosum in horses with pythiosis. AB - Reactions to Pythium insidiosum by sera from horses with active pythiosis were investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) and immunoblotting. Five strains of P. insidiosum were grown in nutrient broth and then sonicated. After centrifugation, supernatant antigens were separated by SDS-PAGE. An exoantigen of Conidiobolus coronatus was also tested. Bands with molecular weights between 97,000 and 14,000 were identified by Coomassie blue and silver staining. After being transferred to nitrocellulose, the antigens were reacted against sera from six horses with pythiosis, sera from four horses cured a year earlier by vaccination, and sera from five healthy horses. The sera from horses with pythiosis recognized at least 20 antigens in all strains. Three antigens with molecular weights of 32,000, 30,000, and 28,000 appeared to be immunodominant and specific. Sera from horses cured by immunotherapy showed only five very weak bands, three of them the 32,000 molecular-weight (32K), 30K, and 28K antigens. No bands were observed with sera from healthy horses or sera from horses with a variety of other infections. Sera from horses with pythiosis cross-reacted with the 44K antigen of C. coronatus. The immunodominant antigens described here may be useful for diagnostic purposes and in immunotherapy for this oomycotic infection in horses. PMID- 1452670 TI - Characterization and distribution of Pasteurella species recovered from infected humans. AB - During a 3-year period, all Pasteurella strains recovered at the Clinical Microbiological Laboratory, Lund, Sweden, were studied biochemically with respect to their relationship to the recently described taxa of this genus. Of 159 strains recovered from 146 infected humans, 95 were identified as Pasteurella multocida subsp. multocida, 21 as Pasteurella multocida subsp. septica, 28 as Pasteurella canis, 10 as Pasteurella stomatis, and 5 as Pasteurella dagmatis. The homology within and between the Pasteurella species regarding cellular fatty acids and enzymatic activities was also studied. Strains of the different Pasteurella species were indistinguishable from each other regarding fatty acid composition; all strains contained major amounts of C14:0, C16:1, C16:0, and 3-OH C14:0 acids and minor amounts of C18:2, C18:1, and C18:0 acids. Neither did the enzymatic activities distinguish between strains belonging to different species. In addition, of 56 strains examined, toxin production was demonstrated only in 1 strain each of P. multocida subsp. multocida and P. canis. Except for one severe case of necrotizing cellulitis involving P. dagmatis, P. multocida subsp. multocida or P. multocida subsp. septica was recovered in the more serious cases of infection. Except for P. canis, which in all cases was associated with dog bites, most Pasteurella strains were recovered in cases of infection associated with cat bites or scratches. Pasteurella strains occurred in four infected patients without evident connections with animals. PMID- 1452671 TI - Comparison of cytobrushes with swabs for recovery of endocervical cells and for Chlamydiazyme detection of Chlamydia trachomatis. AB - Endocervical swab and cytobrush specimens from 1,301 symptomatic women were microscopically analyzed for adequacy and tested using Chlamydiazyme (CZ) (Abbott Laboratories). When the swab specimen was collected first, blocking antibody confirmed CZ-positive results were obtained from 48 (8.0%) of 599 patients, 42 (87.5%) from swabs and 46 (95.8%) from cytobrushes (not significant). When the swab specimen was collected second, confirmed CZ-positive results were obtained from 46 (6.6%) of 702 patients, 44 (95.6%) from swabs and 41 (89.1%) from cytobrushes (not significant). Cytobrushes offered no significant advantage over swabs for CZ detection of Chlamydia trachomatis. PMID- 1452672 TI - Differential susceptibilities of Mycobacterium avium and Mycobacterium intracellulare to sodium nitrite. AB - Sixty-seven of 72 strains of Mycobacterium avium (93.1%) were resistant to sodium nitrite at a concentration of 3 mg/ml in 7H11 agar medium, while 57 of 59 strains of Mycobacterium intracellulare (96.6%) were susceptible to the agent. The difference in the susceptibilities of M. avium and M. intracellulare to sodium nitrite is therefore useful for the differentiation of the two species. PMID- 1452673 TI - Detection of Toxoplasma gondii in cerebrospinal fluid from AIDS patients by polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to detect Toxoplasma gondii DNA in cerebrospinal fluid (CSF) from 14 patients with AIDS by amplification of the repetitive B1 gene. Positive PCRs were obtained in CSF from four of nine patients with toxoplasmic encephalitis. CSF samples from five control patients were negative for T. gondii DNA by PCR. PMID- 1452674 TI - Evaluation of a chemiluminescent probe assay for identification of Histoplasma capsulatum isolates. AB - Fifty-three of 54 isolates of fungi were correctly identified with an acridinium ester-labelled probe for Histoplasma capsulatum (Accuprobe; Gen-Probe, San Diego, Calif.). One isolate of Aspergillus niger was incorrectly identified as H. capsulatum. Age of the culture, medium for isolation, and morphologic state did not affect the results. PMID- 1452675 TI - Experimental Borrelia burgdorferi infection of outbred mice. AB - Infectivity of Borrelia burgdorferi strain 297 in normal outbred ddY mice was examined. Strain 297 was inoculated intraperitoneally in 3-week-old outbred ddY mice. B. burgdorferi was routinely cultured from the heart and urinary bladder 5 to 84 days postinoculation. The combined isolation rate from both heart and urinary bladder was significantly higher than the rate from spleen, kidney, liver, urine, and blood samples. Three- and 10-week-old mice were infected with inocula of 10(4) and 10(5) or more, respectively. Passive transfer of undiluted and 10-fold-diluted anti-297 rabbit serum and active immunization of 50 to 100 micrograms of lyophilized whole cells completely protected mice from infection with B. burgdorferi. These results suggest that the outbred mouse is a convenient model for experimental infection with B. burgdorferi. PMID- 1452676 TI - Fatal disseminated infection caused by Myceliophthora thermophila, a new agent of mycosis: case history and laboratory characteristics. AB - We report a case of human infection caused by the hyphomycete Myceliophthora thermophila. A 7-year-old male with neurofibromatosis (type 1) was diagnosed in 1987 with acute myeloblastic leukemia associated with the chromosomal abnormality monosomy 7. The patient experienced multiple serious infections over a three-year period before expiring in 1990 while in the end stage of leukemia. Autopsy findings included fungal vegetations of the left atrium, ascending aorta, and pulmonary arteries and fungal invasion of both lungs. Cultures yielded M. thermophila. We believe that this is the first reported fatality caused by M. thermophila. PMID- 1452677 TI - Uncommon Campylobacter species in infant Macaca nemestrina monkeys housed in a nursery. AB - Studies were conducted to characterize 18 isolates of Campylobacter spp. that could not be identified as either Campylobacter jejuni or C. coli. The isolates were cultured from specimens from 13 of 18 infant nonhuman primates during a prospective epidemiologic study reported previously. Phenotypic tests, DNA hybridization, and analysis of DNA coding for rRNA identified the isolates as C. butzleri (seven isolates), C. hyointestinalis (seven isolates), and C. fetus subsp. fetus or C. fetus subsp. fetus-like organisms (four isolates). Ribotype and polyacrylamide gel electrophoresis patterns indicated that there was heterogeneity among the isolates of C. butzleri and C. fetus subsp. fetus-like organisms. PMID- 1452678 TI - Detection of diacetyl (caramel odor) in presumptive identification of the "Streptococcus milleri" group. AB - The caramel odor associated with the "Streptococcus milleri" group was shown to be attributable to the formation of the metabolite diacetyl. Levels of diacetyl in the 22- to 200-mg/liter range were produced by 68 strains of the "S. milleri" group; apart from one strain of Streptococcus mutans, all 92 other strains of streptococci belonging to 12 species produced < 13 mg of diacetyl per liter. Quantitation of diacetyl levels from cultures of streptococci is suggested as a rapid presumptive test for the "S. milleri" group. PMID- 1452679 TI - Use of the E test to predict high-level resistance to aminoglycosides among enterococci. AB - The E test and the reference agar dilution methods were compared for detecting high-level aminoglycoside resistance (HLAR) among 71 selected clinical isolates, including 62 Enterococcus faecalis and 9 Enterococcus faecium isolates. High level gentamicin resistance alone was found in 11% (5 E. faecalis and 3 E. faecium strains) and high-level streptomycin resistance was found in 42% (28 E. faecalis, 2 E. faecium strains) of the strains tested, and 31% of the strains demonstrated high-level resistance to both antimicrobial agents (21 E. faecalis and 1 E. faecium strains). The E test detected all HLAR populations, but the streptomycin strip may require recalibration to achieve absolute MIC comparisons with the reference value (twofold less) or the use of an alternative interpretive resistance breakpoint, e.g., > 1,000 micrograms/ml. By the E test, MIC results indicate that ampicillin, imipenem, penicillin, piperacillin, and vancomycin remain active against the HLAR E. faecalis isolates; however, these tested drugs were less effective on the HLAR E. faecium isolates (< 50%). PMID- 1452680 TI - Processing urine specimens: overnight versus two-day incubation. PMID- 1452681 TI - In vitro susceptibility testing of Haemophilus influenzae: review of new National Committee for Clinical Laboratory Standards recommendations. PMID- 1452682 TI - Stability of dried blood spot specimens for detection of human immunodeficiency virus DNA by polymerase chain reaction. AB - Blood sampling on filter paper has many advantages for the detection of perinatal human immunodeficiency virus (HIV) infection by the polymerase chain reaction (PCR). However, if the method is to be widely used, an assessment of its performance under field conditions is required. To simulate conditions in the field, 50-microliters aliquots of whole blood containing low levels of HIV proviral DNA (4 to 1,024 copies per 100,000 nucleated cells) were spotted onto filter paper; dried; and subjected to heat, humidity, and prolonged storage at room temperature. After exposure, the DNA was recovered and amplified with primers to human leukocyte antigen DQ alpha- and HIV-specific sequences. Treatment at 37 degrees C and 60% humidity for 7 days, storage for 12 weeks at 22 degrees C, and freeze-thawing twice had no adverse effect on PCR reactivity when compared with the results obtained with reference spots stored at -20 degrees C. The lower limits of HIV detection in all tests ranged from 4 to 16 HIV copies per 100,000 cells. Fixation in 70% ethanol improved the amplification of low levels of HIV DNA and reduced biohazard risks. These findings suggest that dried blood spots will provide a powerful new resource for testing for HIV by PCR, especially in remote areas where refrigeration and immediate sample processing are unavailable. PMID- 1452683 TI - Western immunoblot analysis and serologic characterization of Blastomyces dermatitidis yeast form extracellular antigens. AB - A major 98-kDa extracellular protein antigen of Blastomyces dermatitidis was shown in Western blot (immunoblot) analysis to be highly reactive with serum antibodies from patients with blastomycosis. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of yeast form B. dermatitidis culture filtrates and cell extracts demonstrated over 50 proteins, only 24 of which were immunoreactive. Of these, a 98-kDa protein was found to be the most specific and was isolated. This protein was found in both broth culture filtrates and extracts of yeast forms. Western blot tests with this antigen detected serum antibodies in 91% of 32 patients with clinically proven blastomycosis, in contrast to an enzyme linked immunosorbent assay (ELISA) with DEAE-purified antigen, which detected 88% of the cases. The Western blot test also exhibited lower reactivity with a panel of sera from patients with heterologous fungal infections that were cross reactive in the ELISA with DEAE-purified B. dermatitidis antigen. The 98-kDa protein electroeluted from polyacrylamide gels was identical to the diagnostic A antigen used in the blastomycosis immunodiffusion test. Comparison of the 98-kDa antigen with a previously described 120-kDa yeast form cell wall protein antigen of B. dermatitidis showed that these two antigens are almost identical. PMID- 1452684 TI - Salmonella serogroups C2 and C3 identified by agglutination using an immunoglobulin G3(kappa) monoclonal antibody (32-1-E3) reactive with a somatic factor 8-like polysaccharide antigen. AB - An immunoglobulin G3(kappa) monoclonal antibody (MAb), MAb 32-1-E3, which was prepared in BALB/c mice by using a heated, alcohol-acetone-extracted Salmonella newport CDC 50 antigen, reacted with protein-free lipopolysaccharides from Salmonella groups C2 (O:6,8) and C3 (O:-,8) but not with those from any other serogroup tested. Sodium periodate did not inhibit antigen reactivity, which was consistent with its identity as the abequose-containing disaccharide O:8 antigen. Reactivity was inhibited by competition with serogroup C2 (O:6,8) and C3 (O:-,8) antigens but not with non-O:8 antigens. Reactivity was also inhibited by preincubation of the antigen with polyclonal rabbit antiserogroup C2 or C3 antibodies but not with antisera to serogroup C1 or other Salmonella serogroups. The MAb agglutinated with all strains of Salmonella serogroups C2 and C3 tested but not with other bacteria. Agglutination was inhibited by preabsorbing the MAb with either of two serogroup C3 Salmonella strains, S. virginia CDC 189 or S. haardt MDL 83A4545, which contain only O:8, but not by preabsortion with O:8 negative S. cholerasuis MDL 81A7623 (group C1; O:6,7), S. paratyphi type B CDC 157 (group B; O:1,[4],5,12), or Escherichia coli (O:157) (which contains no Salmonella serogroup antigens). The MAb reacted strongly (4+ agglutination) with all 140 wild-type strains of group C2 and C3 Salmonella spp. tested and showed no reaction with any of 1,324 wild-type strains of non-C2 or non-C3 Salmonella spp. tested. The MAb is useful as a replacement for absorbed, polyclonal, single factor O:8 antiserum to discriminate Salmonella serogroups C2 and C3 from serogroup C1. PMID- 1452685 TI - Comparison of epidemiological markers of Salmonella strains isolated from different sources in Spain. AB - A comparative study of the phage types, antimicrobial susceptibility patterns, and plasmid profiles of 171 strains of Salmonella isolated from food, epidemic outbreaks, and water-contaminated environments as well as sporadic human isolates was carried out to determine the most adequate marker in epidemiological investigations. Typing based on the plasmid profiles appears to be the most effective method for grouping strains with the same serotype obtained from a single outbreak and from environmental sources. However, none of the three markers tested allow us total discrimination and identification of related strains from a common source for epidemiological tracing. Therefore, the combined use of the three methods is necessary for determining whether common source isolates are related. PMID- 1452686 TI - Production of monoclonal antibody to a phenolic glycolipid of Mycobacterium tuberculosis and its use in detection of the antigen in clinical isolates. AB - A monoclonal antibody (MAbIII604) specific to phenolic glycolipid Tb (PGL-Tb), a Mycobacterium tuberculosis-specific antigen, was produced and used in the detection of the antigen. MAbIII604 reacted with the PGL-Tb antigen but not with other phenolic glycolipids from Mycobacterium leprae, M. bovis, and M. kansasii, thus indicating the specificity of the monoclonal antibody to PGL-Tb. A dot enzyme-linked immunosorbent assay with MAbIII604 was employed to detect the PGL Tb antigen in lipids purified from M. tuberculosis clinical isolates. Of 50 isolates, 32 (64.0%) showed clear evidence of the PGL-Tb antigen by the dot enzyme-linked immunosorbent assay, but there were marked variations in the intensities and sizes of spots. This suggests differences in PGL-Tb antigen production among M. tuberculosis strains even when they are grown in the same culture media and conditions. This was most evident from the fact that in only eight (16.0%) of the isolates examined was the PGL-Tb antigen detectable by thin layer chromatography, which is much less sensitive for the detection of glycolipid antigens. This study shows that monoclonal antibodies specific to PGL Tb are useful in detecting the antigen in lipid extracts and that there is a marked variation in the PGL-Tb production among M. tuberculosis clinical isolates. PMID- 1452687 TI - Functional and serological analysis of type II immunoglobulin G-binding proteins expressed by pathogenic group A streptococci. AB - Bacterial immunoglobulin-binding proteins expressed on the surface of group A streptococci represent a heterogeneous family of functionally related proteins. In this report, we describe efficient methods for extracting immunoglobulin binding proteins and classifying them functionally and antigenically. A common characteristic of immunoglobulin-binding proteins expressed by group A streptococci appears to be the absence of internal methionine residues in the binding protein. This has enabled development of a rapid, efficient, cyanogen bromide-based extraction procedure for solubilizing these molecules from intact bacteria. Studies carried out with a series of monospecific polyclonal antibodies prepared in chickens have identified two major antigenic classes of immunoglobulin-binding proteins. The methods described in this report facilitate a rapid functional and serological screening of immunoglobulin-binding proteins that should now enable detailed epidemiological studies of the importance of these molecules in group A streptococcal infections and their relationship to other surface proteins, in particular, the antiphagocytic M protein. PMID- 1452688 TI - Diagnosis of early Lyme disease by polymerase chain reaction amplification and culture of skin biopsies from erythema migrans lesions. AB - Current laboratory diagnosis of Lyme disease relies on tests for the detection of antibodies to Borrelia burgdorferi, the etiologic agent of the disease. These tests are often unreliable because of a lack of sensitivity and specificity and test-to-test variability. The purpose of this study was to evaluate the sensitivity and specificity of polymerase chain reaction (PCR) amplification for detection of B. burgdorferi in skin biopsy specimens. Forty-six 2-mm skin biopsy samples were obtained from 44 patients with a clinical diagnosis of erythema migrans, 9 of whom were receiving antibiotic therapy at the time of biopsy. Specimens were ground in BSK medium with separate aliquots taken for culture and PCR. Of the specimens from the untreated group, 57% (21 of 37) were positive by culture and 22% (8 of 37) were culture negative; 22% (8 of 37) of the cultures were uninformative because of contamination. By comparison, 22 (59%) of 37 specimens were positive by PCR amplification. Of 21 culture-positive samples, 13 (62%) were also positive by PCR analysis. Thus, the sensitivity of the PCR was 59 to 62%, based on either a clinical or cultural diagnosis of untreated Lyme disease. None of the nine specimens from antibiotic-treated patients grew in culture, whereas two of the nine were positive by PCR analysis. Given the complexity and time required for culture, PCR is a promising technique for the diagnosis of early Lyme disease. PMID- 1452689 TI - Preliminary evaluation of the ligase chain reaction for specific detection of Neisseria gonorrhoeae. AB - Rapid identification of Neisseria gonorrhoeae in clinical specimens is essential for effective control. Traditional culture requires a minimum of 24 h, and for some specimens harboring gonococci, the gonococci fail to grow or are misidentified. The recently described ligase chain reaction (LCR) is a highly specific and sensitive DNA amplification technique which was evaluated as an alternative to routine culture. Three LCR probe sets were used. Two of the probe sets were directed against the multi-copy Opa genes (Omp-II), while the third set was targeted against the multicopy Pilin genes. Each LCR probe set was evaluated with 260 microorganisms including 136 global isolates of N. gonorrhoeae, 41 isolates of N. meningitidis, and 10 isolates of N. lactamica; 26 nonpathogenic Neisseria strains; and 47 isolates of non-Neisseria species that may reside in clinical specimens. Amplification products were detected by using the IMx LCR format (Abbott Laboratories, Abbott Park, Ill.). Strains of N. gonorrhoeae were assayed at 270 cells per LCR (approximately 6.7 x 10(4) CFU/ml) with the Opa and Pilin probes, producing signals at least 21 and 15 times above background, respectively. In contrast, only background values were observed when testing the probe sets with 124 nongonococcal strains at 1.3 x 10(6) cells per LCR (approximately 3.2 x 10(8) CFU/ml). One hundred urogenital specimens were assayed by LCR, and compared with culture, the three probes were 100% sensitive (8 of 8) and 97.8% specific (90 of 92), resulting in an agreement of 98% (98 of 100). On the basis of the results of these preliminary studies, LCR has the potential to be an accurate and rapid DNA probe assay for the detection of N. gonorrhoeae in clinical specimens. PMID- 1452690 TI - Effects of fixation on polymerase chain reaction detection of Mycobacterium leprae. AB - The effects of standard fixatives (10% neutral buffered formalin, ethanol and mercury based) on the detection of Mycobacterium leprae DNA by the polymerase chain reaction (PCR) were studied. Mercury-based fixatives (Zenker's and Carnoy Lebrun's fluids) strongly inhibited PCR amplification of M. leprae DNA. Ten percent neutral buffered formalin was inhibitory, but significant inhibition was observed only when fixation times exceeded 24 h. Ethanol-based fixatives provided the best medium for holding specimens for subsequent PCR with both free bacilli and skin biopsy specimens containing M. leprae. The M. leprae-specific, 360-bp region of the 18-kDa protein gene could be amplified from paraffin-embedded sections of formalin-fixed skin biopsy specimens from patients with either multibacillary or paucibacillary infections when proper fixation conditions were used. Results of the study demonstrate that tissues properly fixed with two standard fixatives (10% neutral buffered formalin and 50 or 70% ethanol) can be analyzed by PCR for the presence of M. leprae with no loss in specificity and only minimal diminution in sensitivity compared with the specificities and sensitivities obtained by use of freshly prepared, unfixed specimens. PMID- 1452691 TI - Differentiation of Moraxella nonliquefaciens, M. lacunata, and M. bovis by using multilocus enzyme electrophoresis and hybridization with pilin-specific DNA probes. AB - Genetic relationships among strains of Moraxella nonliquefaciens, M. lacunata, and M. bovis were studied by using multilocus enzyme electrophoresis and DNA-DNA hybridization. The 74 isolates analyzed for electrophoretic variation at 12 enzyme loci were assigned to 59 multilocus genotypes. The multilocus genotypes were grouped in four major clusters, one representing strains of M. nonliquefaciens, two representing strains of M. lacunata, and one comprising strains of M. bovis and the single strain of M. equi analyzed. DNA-DNA hybridization with total genomic probes also revealed four major distinctive entities that corresponded to those identified by multilocus enzyme electrophoresis. The two distinct clusters recognized among the M. lacunata strains apparently corresponded to the species previously designated M. lacunata and M. liquefaciens. Distinction of the four entities was improved by hybridization with polymerase chain reaction products of nonconserved parts of pilin genes as DNA probes. With these polymerase chain reaction probes, new isolates of M. nonliquefaciens, M. lacunata, M. liquefaciens, and M. bovis can be identified easily by hybridization. PMID- 1452692 TI - Comparative evaluation of a chemiluminescent DNA probe and an exoantigen test for rapid identification of Histoplasma capsulatum. AB - A chemiluminescent DNA probe (Accuprobe) assay developed by Gen Probe, Inc., for the rapid identification of Histoplasma capsulatum was evaluated and compared with the exoantigen test by using 162 coded cultures including Histoplasma capsulatum var. capsulatum, Histoplasma capsulatum var. duboisii, Histoplasma capsulatum var. farciminosum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis, and morphologically related saprobic fungi. Each test uses a chemiluminescent, acridinium ester-labeled, single-stranded DNA probe that is complementary to the rRNA of the target organism. Lysates of the test cultures were prepared by sonication with glass beads and heat treated. After the rRNA was released from the target organism, the labeled DNA probe combined with the target H. capsulatum rRNA to form a stable DNA-RNA hybrid. A hybridization protection assay was used, and the chemiluminescence of hybrids was measured initially with a Leader 1 luminometer as relative light units and later during the investigation with a probe assay luminometer as probe light units. Of the 162 coded mycelial cultures tested by the Accuprobe assay, 105 were identified as H. capsulatum. The test could be performed with an inoculum of a few square millimeters (1 to 2 mm2) of growth. In the primary evaluation, the Accuprobe identified 103 of the 105 cultures as H. capsulatum within 2 h. The remaining two cultures, contaminated with bacteria, had to be purified before the Accuprobe assay identified them correctly as H. capsulatum. Since each coded culture was concurrently tested for H. capsulatum, B. dermatitidis, and C. immitis exoantigens, the identification of all three dimorphic pathogens was provided simultaneously. Of the 162 coded cultures tested, 105 were identified by the exoantigen test as H. capsulatum, 12 were identified as B. dermatitidis, 13 were identified as C. immitis, and 32 were negative for H. capsulatum, B. dermatitidis, and C. immitis. The bacterial contamination in two isolates did not interfere with the exoantigen testing. The exoantigen test required 7- to 10-day old colonies and required 48 to 72 h of incubation before definitive identification was obtained. PMID- 1452693 TI - Evaluation of the RapID ANA II and API ZYM systems for identification of Actinomyces species from clinical specimens. AB - Classification and identification of fermentative actinomycetes are labor intensive and problematic. In this study, we evaluated the applicability and reliability of the RapID ANA II system (Innovative Diagnostic Systems, Inc., Atlanta, Ga.) and the discriminatory value of the API ZYM system (Societes Analytab Products Inc., La Balme Les Grottes, France) in the identification of Actinomyces-like bacteria by using conventional methods as a reference. Eighty five strains, including 71 isolates from mixed anaerobic infections and 14 reference strains, were tested. The RapID ANA II system correctly identified all Actinomyces odontolyticus strains and 65% of Actinomyces israelii strains. All Arcanobacterium haemolyticum strains were misidentified as Actinomyces pyogenes. The most common isolates in the study were Actinomyces meyeri-like organisms, 84% of which, however, were aerotolerant. The identification of these aerotolerant strains thus remains unresolved and warrants further studies. New characteristics and changes to the conventional API ZYM enzyme profiles are suggested. The API ZYM enzyme profiles of A. odontolyticus and A. israelii were very similar, the only discriminating enzyme being alpha-fucosidase. In differentiation between A. pyogenes and Arcanobacterium haemolyticum, the production of beta-glucuronidase by the former and the production of acid phosphatase by the latter are suggested as new helpful characteristics for use in clinical laboratories. In summary, the RapID ANA II and API ZYM systems can be used as rapid preliminary methods in the identification of Actinomyces species but accurate identification requires supplementary conventional tests and gas-liquid chromatography. PMID- 1452694 TI - Risk factors for sporadic Campylobacter infections: results of a case-control study in southeastern Norway. AB - In 1989 and 1990, a case-control study designed to identify risk factors for sporadic infections with thermotolerant Campylobacter bacteria was conducted in three counties in southeastern Norway. The investigation was confined to infections which were acquired in Norway. A total of 52 bacteriologically confirmed cases and 103 controls matched by age, sex, and geographic region were interviewed. The following risk factors were found to be independently associated with illness in conditional logistic regression analysis: consumption of sausages at a barbecue (odds ratio [OR] = 7.64; P = 0.005), daily contact with a dog (OR = 4.26; P = 0.024), and eating of poultry which was brought into the house raw (frozen or refrigerated) (OR = 3.20; P = 0.024). The risk associated with consumption of sausages at a barbecue could not be attributed to cross contamination from poultry products. By univariate analysis, consumption of poultry which was brought raw and frozen was associated with illness (OR = 2.42; P = 0.042), even though freezing substantially reduces the number of viable campylobacters. When poultry consumption was examined by country of origin, eating of poultry produced in Denmark or Sweden was strongly associated with illness (OR = 13.66; P = 0.014), whereas consumption of poultry produced in Norway was not (OR = 1.33; P = 0.41). PMID- 1452695 TI - Streptococcal erythrogenic toxin genes: detection by polymerase chain reaction and association with disease in strains isolated in Canada from 1940 to 1991. AB - The presence of genes encoding pyrogenic exotoxins type A (speA), B (speB), and C (speC) and streptolysin O (slo) was determined by the polymerase chain reaction (PCR) to target specific sequences in 152 strains of group A streptococci. These included reference strains, representative M and T type strains, and strains associated with scarlet fever and pharyngitis collected between 1940 to 1991 and included strains from patients with severe invasive streptococcal infections. PCR amplicons were detected by agarose gel electrophoresis, and specificity was established by restriction fragment analysis. The frequency of occurrence for each target gene among all strains tested was 33.6% for speA, 99.3% for speB, 28.9% for speC, and 100% for slo. Strains of non-group A streptococci, recognized toxigenic bacterial pathogens, and pneumolysin-producing Streptococcus pneumoniae strains were negative for all targeted gene sequences. Detection limits in the PCR were found to be 100 pg of total nucleic acids for the speB and speC genes and 1 ng for the speA and slo genes. Isolates associated with scarlet fever, pharyngitis, and severe invasive infections showed statistically significant differences in the presence of speA, with scarlet fever strains having the highest association (81.3%), severe infections the next highest association (42.9%), and pharyngitis the lowest association (18.4%). Although no significant differences were observed in speC frequencies in isolated associated with the three disease categories, a genotype of speB slo was significantly higher in isolates associated with pharyngitis (54.1%) than in strains associated with scarlet fever (18.8%) or severe invasive disease (23.8%). Streptolysin O targets were present in all the isolates tested, and only a single strain (T-11-M-11) was devoid of targeted speB sequences, thereby demonstrating that neither speB nor slo is associated with any particular clinical presentation. PMID- 1452696 TI - Detection of serum Candida antigens by enzyme-linked immunosorbent assay and a latex agglutination test with anti-Candida albicans and anti-Candida krusei antibodies. AB - Serum samples from 197 patients with and without candidiasis were assayed for Candida albicans mannan and Candida krusei mannan by an enzyme-linked immunosorbent assay (ELISA) and a latex agglutination test (LA) and for D arabinitol by the enzymatic fluorometric method. Of the 43 patients positive for C. albicans mannan (> or = 0.2 ng/ml), 34 were infected with C. albicans and 9 were infected with Candida tropicalis. C. krusei mannan (> or = 0.3 ng/ml) was detected in 10 patients infected with Candida parapsilosis, 2 patients infected with Candida guilliermondii, and 1 patient infected with C. krusei. With both anti-C. albicans antibodies and anti-C. krusei antibodies, the sensitivities of ELISA and LA for detection of invasive candidiasis (58 patients) were 74 and 38%, respectively. No false-positive reactions were observed by the ELISA or the LA. The sensitivity and specificity of the D-arabinitol/creatinine ratio (> or = 1.5 mumol/mg) to invasive candidiasis were 50 and 91%, respectively. The ELISA with antibodies against both C. albicans and C. krusei may be useful in diagnosing invasive candidiasis caused by medically important Candida strains excluding Candida glabrata. PMID- 1452697 TI - Collaborative comparison of broth macrodilution and microdilution antifungal susceptibility tests. AB - A collaborative comparison of macro- and microdilution antifungal susceptibility tests was performed in five laboratories. MICs of amphotericin B, fluconazole, flucytosine, and ketoconazole were determined in all five centers against 95 coded isolates of Candida spp., Cryptococcus neoformans, and Torulopsis glabrata. A standard protocol with the following National Committee for Clinical Laboratory Standards Subcommittee on Antifungal Susceptibility Testing recommendations was used: an inoculum standardized by spectrophotometer, buffered (RPMI 1640) medium (pH 7.0), incubation at 35 degrees C, and an additive drug dilution procedure. Two inoculum sizes were tested (1 x 10(4) to 5 x 10(3) to 2.5 x 10(3) CFU/ml) and three scoring criteria were evaluated for MIC endpoint determinations, which were scored as 0 (optically clear), < or = 1 (slightly hazy turbidity), and < or = 2 (prominent decrease in turbidity compared with that of the growth control). Overall intra- and interlaboratory reproducibility was optimal with the low density inoculum, the second-day readings, and MICs scored as either 1 or 2. The microdilution MICs demonstrated interlaboratory agreement with most of the four drugs higher than or similar to that of the macrodilution MICs. In general, there was good interlaboratory agreement with amphotericin B, fluconazole, and flucytosine; ketoconazole gave more variable results. PMID- 1452698 TI - Comparison of commercial serological tests for detection of Helicobacter pylori antibodies. AB - Serological testing for Helicobacter pylori infection is one of the diagnostic methods of choice. Various commercial kits that use different antigens have been developed, but data on their diagnostic accuracy and direct comparisons between the tests are lacking. We aimed to evaluate the sensitivity, specificity, and predictive value of three immunoglobulin G enzyme-linked immunosorbent assay kits: Pylori stat, Helico-G, and Premier H. pylori. Serum samples and gastric biopsy findings from 76 patients were evaluated. We found by using a priori cutoff values that the Pylori stat, Helico-G, and Premier kits had overall sensitivities of 96, 96, and 88%, respectively, and specificities of 94, 86, and 96%, respectively, compared with gastric biopsy findings. For 232 serum samples, the Pylori stat test and a previously validated standard serological assay on which the test was based disagreed in 3% of the cases, while for 76 samples that were tested, Helico-G and a previously validated standard assay on which it was based disagreed in 8% of the cases. The intra- and interassay precision of each of the test kits was high. We conclude that serology based on any of these commercial tests represents a reliable and valid method for the diagnosis of H. pylori whether or not highly purified antigens are used. PMID- 1452699 TI - Sensitive and specific serodiagnosis of invasive amebiasis by using a recombinant surface protein of pathogenic Entamoeba histolytica. AB - A recombinantly expressed protein, recEh-P1, representing part of an immunodominant surface antigen of pathogenic Entamoeba histolytica, was used for serodiagnosis of invasive amebiasis. Expression was performed under the control of a T7-RNA promoter by using a modified procaryotic expression vector, designated pHisT7. This vector allowed high-yield expression of recEh-P1 fused to a stretch of sequence containing eight histidine residues, which facilitated purification by metal chelate affinity chromatography on Ni2+ columns under highly denatured conditions. Purified recEh-P1 was found to be water soluble after prolonged dialysis and was used as the antigen for the detection of antiamebic serum antibodies by immunoblotting and enzyme-linked immunosorbent assay. In both tests all sera of patients with invasive amebiasis reacted to recEh-P1 whereas none of those collected from healthy controls, including individuals with noninvasive amebiasis, or from patients suffering from bacterial or protozoan infections unrelated to E. histolytica did so. PMID- 1452700 TI - Antibody response to Brucella outer membrane proteins in bovine brucellosis: immunoblot analysis and competitive enzyme-linked immunosorbent assay using monoclonal antibodies. AB - Sera from Brucella-infected bovines were analyzed by immunoblotting by using sonicated cell extracts of B. melitensis or B. abortus and a competitive enzyme linked immunosorbent assay (ELISA) with monoclonal antibodies against outer membrane proteins (OMPs) with molecular masses of 10, 16.5, 19, 25 to 27, 36 to 38, and 89 kDa. Antibody responses against OMPs were compared with antibody responses against smooth lipopolysaccharide. Immunoblot analysis indicated that the antibody response in infected animals was largely different from one animal to another. The antigens of concern were OMPs with molecular masses of 10, 16.5, 19, 25 to 27, 36 to 38, and 89 kDa and other proteins with molecular masses of between 40 and 80 kDa. According to the specificity of the competitive ELISA, OMPs useful for the detection of infected animals are the OMPs of 10, 16.5, 19, 25 to 27, and 36 to 38 kDa. A competitive ELISA with the anti-89 kDa monoclonal antibody was not specific. Results of the competitive ELISA confirmed the individual variability of the humoral immune response against OMPs. It therefore seems that a combination of several protein antigens is necessary for the development of an immunoassay with a sensitivity comparable to that of the smooth lipopolysaccharide ELISA. PMID- 1452701 TI - Detection of Toxoplasma gondii parasitemia by gene amplification, cell culture, and mouse inoculation. AB - Diagnosis of Toxoplasma gondii infection is difficult, especially in immunosuppressed people. The AIDS epidemic has increased the number of people at risk and increased the need for better diagnostic methods. We have compared three methods for detection of T. gondii parasitemia. Rabbits were infected subcutaneously with 10(4) T. gondii tachyzoites. Blood samples were obtained, and buffy coat or leukocyte fractions were prepared. We sought the T. gondii B1 gene by gene amplification by the polymerase chain reaction, and we sought viable T. gondii cells by inoculating fibroblast cell cultures and by mouse inoculation. Thirty-two blood samples were obtained from seven infected rabbits, and 18 were obtained from four control, uninfected rabbits. Parasitemia was detected in 20 of 32 samples (62%) from infected samples by mouse inoculation, 12 of 32 samples (37%) by gene amplification and detection, and 8 of 32 samples (25%) by cell culture. Mouse inoculation requires use of live animals and has a long turnaround time. Currently, cell culture is the least sensitive but most practical and widely available method for the detection of T. gondii parasitemia. Gene amplification and detection was more sensitive than cell culture and may become available in clinical laboratories as techniques are developed further and automated. PMID- 1452702 TI - The magnetic immuno polymerase chain reaction assay for direct detection of salmonellae in fecal samples. AB - Direct polymerase chain reaction (PCR)-based detection with fecal specimens is hampered by inhibitory compounds, such as bilirubin and bile salts. These fecal compounds showed significant inhibition of PCR at low concentrations (10 to 50 micrograms/ml). For direct PCR analysis, fecal samples must be diluted 500-fold to overcome inhibition. Therefore, the magnetic immuno PCR assay (MIPA), which combines immunomagnetic separation by using specific monoclonal antibodies and PCR, was used to directly detect salmonellae in feces from humans. Immunomagnetically extracted stool samples needed to be diluted only 10-fold when 1 microgram of T4 gene 32 protein was added to the PCR. The MIPA sensitivity obtained was 10(5) CFU/ml of feces. A panel of monoclonal antibodies specific for Salmonella serogroups A to E was used to extract salmonellae from clinical samples. MIPA detection of salmonellae occurred with 11 out of 14 stool samples stored at 4 degrees C for 2 months. MIPA detection of salmonellae in stool samples is a promising, fast method for detection and identification. PMID- 1452703 TI - Comparison of nine antigen detection kits for diagnosis of urogenital infections due to Chlamydia psittaci in koalas. AB - Chlamydia psittaci is the major cause of infectious disease in the koala (Phascolarctos cinereus). It causes four disease syndromes in the koala, namely, conjunctivitis, rhinitis, cystitis, and infertility (females only). Diagnosis of chlamydial infections in koalas relies primarily on isolation of the organism in cell culture. Serology has generally not been useful, and little use has previously been made of the commercially available antigen detection kits. We examined the sensitivity, specificity, and usefulness of three direct fluorescent antibody kits (Vet-IF [Cell Labs], IMAGEN [Celltech], Chlamydia-Direct IF [Bio Merieux]) and six antigen detection enzyme-linked immunosorbent assay (ELISA) kits (Clearview [Unipath], Surecell [Kodak], Pathfinder [Kallestad], Chlamydia EIA [Pharmacia], Chlamydiazyme [Abbott], IDEIA [Celltech]) for the detection of urogenital infections in koalas. Laboratory studies showed that the direct fluorescent-antibody kits were the least sensitive in this case and did not detect fewer than 10(4) elementary bodies per ml, while most ELISA kits detected between 130 and 600 elementary bodies per ml. Field study results showed that the Clearview kit was the most sensitive (91%) compared with the IDEIA (88%) and the Surecell (73%) kits. All three kits were more sensitive than cell culture (36%), highlighting viability loss problems that occur during transport. This study showed that the Clearview kit is sensitive, specific, and easy to use for the detection of type II (urogenital) C. psittaci from koalas in the field and warrants further evaluation. PMID- 1452704 TI - Application of rejection criteria for stool ovum and parasite examinations. AB - We retrospectively determined the yield of 2,015 stool ovum and parasite (O&P) examinations performed over an 11-month period. Two aspects were evaluated: the yield of positive results from multiple specimens per patient versus the result of a single examination, and the yield of positive results from stools submitted after 3 days of hospitalization. There were 131 (6.7%) positive O&P examinations from 75 patients: for 35 patients the single examination was positive; for 18, two of two examinations were positive; and for 15, three of three examinations were positive. The remaining seven patients had at least one negative examination in a series, but pathogenic intestinal parasites were detected in only three of these patients. Seventeen patients with positive O&P examinations were inpatients: seven of nine patients examined for O&P within 3 days of admission had stool specimens that contained recognized pathogens, in contrast to only two of eight patients examined after 3 days of hospitalization. After reviewing the data and informing hospital clinics, wards, and physicians, we instituted the following policy for screening stool specimens submitted for O&P examination. Only one O&P examination was performed for each outpatient visit and for inpatients hospitalized for 3 days or less, and examinations were not performed on stools submitted after 3 days of hospitalization unless the clinician arranged for the examination on the basis of clinical need. Over the 6-month follow-up period, 29.9% of O&P requests were rejected, 22% for patients in hospital for longer than 3 days and 7.9% for multiple O&P requests. Of 265 initially rejected specimens, 22 (8.3%) were examined after the referring physician contacted the laboratory. None of these specimens was positive. We conclude that eliminating O&P examinations of patients hospitalized for more than 3 days and initially performing only one examination per patient significantly reduces the number of examinations performed and reduces laboratory charges without adversely affecting patient care. PMID- 1452705 TI - Evaluation of methods for differentiation of coagulase-positive staphylococci. AB - The purpose of this study was to determine the minimum number of tests that could be used to differentiate between the coagulase-positive strains of staphylococcus: Staphylococcus aureus, Staphylococcus hyicus, and Staphylococcus intermedius. Eighty coagulase-positive strains of each of the three species were examined. The five tests conducted were growth on modified Baird-Parker agar, growth on P agar supplemented with acriflavin, production of acetoin, anaerobic fermentation of mannitol, and presence of beta-galactosidase. Positive test percentages for S. aureus were 100% for growth on modified Baird-Parker agar, 100% for growth on P agar supplemented with acriflavin, 94% for production of acetoin, 99% for anaerobic fermentation of mannitol, and 0% for presence of beta galactosidase. Positive test percentages for S. intermedius were 0% for growth on modified Baird-Parker agar, 0% for growth on P agar supplemented with acriflavin, 1% for production of acetoin, 0% for anaerobic fermentation of mannitol, and 100% for presence of beta-galactosidase. S. hyicus isolates were negative in all five tests. Results from the 240 coagulase-positive staphylococcus strains tested would suggest correct identification of coagulase-positive staphylococci with P agar supplemented with acriflavin and the beta-galactosidase test. These two tests are simple to conduct and result in quick and easy differentiation of the three coagulase-positive staphylococcal species. PMID- 1452706 TI - Cellular fatty acids in Fusobacterium species as a tool for identification. AB - Identification of fusobacteria from clinical specimens currently requires analysis of metabolic end products by gas-liquid chromatography in addition to certain biochemical and enzymatic tests because of the relative biochemical inactivity of these bacteria. Even the finding of pointed, thin gram-negative cells on Gram-stained slides can no longer be relied on for identification of Fusobacterium nucleatum, since at least four other species of fusobacteria have been seen to exhibit similar morphology. We examined 46 clinical isolates and six American Type Culture Collection type strains of fusobacteria by conventional methods and by the Microbial ID Systems MIDI software package for analyzing cellular fatty acid patterns measured by capillary column gas-liquid chromatography. Distinctive patterns of major fatty acids could be used to reliably identify most clinical isolates to the species level. The MIDI system identified 89% of the isolates correctly and provides an alternative to conventional methods. PMID- 1452707 TI - Evaluation of a commercially available complement fixation test for diagnosis of Helicobacter pylori infection and for follow-up after antimicrobial therapy. AB - Commercially available complement fixation test reagents (Institute Virion Ltd., Ruschlikon, Zurich, Switzerland) available in package format were evaluated for the serodiagnosis of Helicobacter pylori infection. The assay was compared with bacterial culture and histological Giemsa stain of gastric biopsy specimens obtained from 930 patients of different ages and from different ethnic groups, with a variety of upper gastrointestinal tract symptoms. The prevalence, sensitivity, specificity, and positive and negative predictive values, respectively, were 35, 71, 90, 80, and 85% for Belgian patients aged 40 years or younger, 50, 81, 93, 92, and 83% for Belgian patients older than 40 years, and 83, 83, 79, 95, and 48% for Mediterranean patients. Using 645 serum specimens from 226 patients, we also evaluated the complement fixation test for its ability to monitor the eradication of H. pylori following antimicrobial therapy. Overall, H. pylori was eradicated from 122 patients while 104 patients remained infected with the organism. A significant decrease in antibody levels was observed 3 to 6 months after the end of therapy in the group of patients from whom H. pylori was eradicated. PMID- 1452708 TI - Value of extended agitation and subculture of BACTEC NR 660 aerobic resin blood culture bottles for clinical yeast isolates. AB - From 10,351 blood cultures, we prospectively studied 1,000 BACTEC NR 660 aerobic resin blood culture bottles (26+ and Peds Plus) for patients suspected of having yeast septicemia to determine whether extended agitation and subculturing would increase the recovery of yeasts. Aerobic bottles were agitated continuously for 144 h. On day 7, 1,000 culture-negative aerobic bottles which had fungal blood culture requests were agitated for an additional 14 days. During this time they were subcultured twice and read twice by BACTEC NR 660. ON days 1 to 7, 81 bottles were cultured positive for yeasts from 36 patients, which included 44 isolates of Candida albicans, averaging 1.4 days to detection, and 12 isolates of Cryptococcus neoformans, averaging 3.8 days to detection. The average detection time for all yeasts was 2.2 days. On days 7 to 21, no yeasts were detected by BACTEC or recovered from the subcultures. We conclude that when continuously agitated for at least 5 full days (120 h), the BACTEC NR 660 aerobic resin bottles reliably isolate yeasts, and it is unnecessary to subculture or hold these bottles beyond 5 days. It also eliminates the need for an additional blood culture system for yeast detection, thus saving (i) confusion in the collection process, (ii) patients' blood and money, and (iii) laboratory technologists' time. PMID- 1452709 TI - Accuracy of the E test for determining antimicrobial susceptibilities of staphylococci, enterococci, Campylobacter jejuni, and gram-negative bacteria resistant to antimicrobial agents. AB - We compared the results of the E test MIC method with the results of agar dilution susceptibility testing for 18 antimicrobial agents against 324 strains of gram-positive and gram-negative bacteria, including 99 strains of staphylococci, 101 strains of antimicrobial-resistant gram-negative bacteria, 40 strains of enterococci, and 84 isolates of Campylobacter jejuni. Overall agreement of MICs (+/- 1 log2 dilution) was 97.3% for staphylococci, 94.6% for gram-negative bacilli, and 100.0% for enterococci. The MIC results for C. jejuni showed an overall agreement of only 82.9%. This was due primarily to a number of offscale values that limited the number of comparisons with clindamycin, trimethoprim-sulfamethoxazole, and tetracycline. Interpretative criteria for the results of the two test methods, however, were similar. Overall, the E test produced MIC results comparable to those of agar dilution when multiresistant organisms were tested. However, it was necessary to add 2% NaCl to the agar when testing oxacillin against staphylococci for both the E test and agar dilution to obtain results comparable to those of the broth microdilution method. PMID- 1452710 TI - Genotypic identification and characterization of species and strains within the genus Candida by using random amplified polymorphic DNA. AB - Random amplified polymorphic DNA (RAPD) was used to better characterize the genotypic relatedness among medically important Candida species. By using short oligomer primers (10-mers) with arbitrarily chosen sequences in the polymerase chain reaction, distinctive and reproducible sets of polymerase chain reaction products were observed for isolates of C. albicans, C. lusitaniae, C. tropicalis, and Torulopsis (Candida) glabrata. The RAPD analysis differentiated a physiologically homogeneous panel of C. parapsilosis into three distinct groups and showed genetic diversity within C. haemulonii. Intraspecies DNA-length polymorphisms were seen for RAPD profiles derived from different isolates of each species. Analysis of RAPDs from a panel of C. albicans, which included 16 laboratory derivatives of two reference strains, showed that the profiles of unrelated strains differed and that the derivatives of each reference strain were identifiable. Minor differences in the RAPD profiles, suggestive of mutations that had occurred during the long-term maintenance of the strains, were detected. Because of its ease and reliability, RAPD analysis should be useful in providing genotypic characters for taxonomic descriptions, for confirming the identities of stock isolates, for typing Candida species in epidemiologic investigations, and for use in the rapid identification of pathogenic fungi. PMID- 1452711 TI - Evaluation of a new monoclonal antibody combination reagent for direct fluorescence detection of Giardia cysts and Cryptosporidium oocysts in human fecal specimens. AB - Giardia lamblia and Cryptosporidium parvum can cause severe symptoms in humans, particularly in the immunologically compromised. Monoclonal antibody reagents offer increased sensitivity and an excellent alternative to conventional staining methods. These reagents are helpful when screening large numbers of patients or those with minimal symptoms. Problems of false-positive and false-negative results with routine staining methods for stool parasites can be eliminated with monoclonal antibody reagents. Known positive formalinized specimens [Giardia sp. (n = 60), Cryptosporidium sp. (n = 55), and mixed Giardia-Cryptosporidium spp. (n = 10)] and negative formalinized specimens (n = 105), of which 46 contained other yeast or human cells or protozoa), were tested by the MERIFLUOR Cryptosporidium Giardia direct immunofluorescence detection procedure. The MERIFLUOR reagent exhibited +/- to 4+ (majority, 2+ to 3+) on all Giardia cysts and 2+ to 4+ (majority, 3+ to 4+) on all Cryptosporidium oocysts. The cysts were generally oval (11 to 15 microns), while the oocysts were round (4 to 6 microns); both showed apple-green fluorescence against a background free of nonspecific fluorescence. All specimens positive for Giardia sp. and/or Cryptosporidium sp. showed fluorescence, and all specimens negative for the two organisms showed no fluorescence. There were eight specimens previously negative by the ova and parasite examination which were positive by the direct fluorescence method; four contained Giardia sp., and four contained Cryptosporidium sp. These positive results were confirmed after the examination of additional trichrome and modified acid-fast smears. The MERIFLUOR reagent was very easy to use, and even with a lower fluorescence intensity for Giardia sp. cysts, no false-negative or false positive results among the specimens tested for either organism were found. PMID- 1452713 TI - Novel coagglutination method for serotyping group B streptococci. AB - A group G streptococcal strain was coated with antibody against six different serotypes (Ia, Ib, II, III, IV, and V) of group B streptococci. The coagglutination patterns of 114 strains of group B streptococci were compared with the serotypes determined after immunoprecipitation. The specificity of the method was 100% and the sensitivity 97%. It was used for the typing of 89 invasive and 101 colonizing isolates. The new method is swift, specific, and highly sensitive. It consumes only minute amounts of antibody. PMID- 1452712 TI - An enzyme-linked immunosorbent assay for enumeration of Pneumocystis carinii in vitro and in vivo. AB - An enzyme-linked immunosorbent assay (ELISA) to quantitate Pneumocystis carinii organisms from culture supernatant and rat lung has been developed. A polyclonal antibody specific to P. carinii was produced in Sprague-Dawley rats by allowing P. carinii-infected animals to recover from infection. This antibody reacted strongly to P. carinii proteins of 50 to 55 kDa and weakly to those of 33 and 116 kDa. The ELISA used this convalescent-phase antibody to quantitate the number of P. carinii organisms in lung homogenates of infected rats and supernatants from infected tissue cultures which were used to screen drugs for P. carinii. The results of the ELISA were compared with those of direct microscopic counting of organisms, and the two methods were highly correlated (r > 0.9). Thus, the ELISA can be used as an alternative method for the quantitation of P. carinii organisms, and it is superior to the conventional microscopic method because it is easier to perform and less labor-intensive. PMID- 1452714 TI - Capsular polysaccharide serotyping scheme for Staphylococcus epidermidis. AB - A scheme for the capsular typing of Staphylococcus epidermidis that is based on direct slide agglutination between proteinase-treated bacterial cells and specific antisera is described. Antisera were prepared from serum from rabbits immunized with two selected strains of encapsulated S. epidermidis isolated from bacteremic patients. Antisera were shown to be type specific and designated type 1 and type 2. Blood isolates of S. epidermidis from hospitals in different locations within the United States and Europe were serotyped, and it was found that over 90% of all strains were of type 1 or type 2. Type-specific antibodies mediated type-specific opsonophagocytosis and killing of S. epidermidis. The specificity was shown to be due to two distinct capsular polysaccharides. The data presented in this report may open a new window on the pathogenesis of S. epidermidis which could lead to the development of new vaccines and therapies. PMID- 1452715 TI - Evaluation of the Wellcolex Colour Salmonella Test for detection of Salmonella spp. in enrichment broths. AB - The Wellcolex Colour Salmonella Test was evaluated for detection of Salmonella spp. in enrichment broths of 1,010 stool samples. In 39 specimens, Salmonella spp. could be isolated from the selenite F broth (SF). Wellcolex agglutination indicative of the presence of Salmonella spp. was noted with the SF in 36 cases, 34 of which were in agreement with the subculture results. Therefore, relative to subculture, the sensitivity and specificity of the Wellcolex-selenite F procedure were 87 and 99%, respectively. Five false-negative results were noted. The gram negative broth (GN) subculture revealed only 23 Salmonella spp. (59% sensitivity). The Wellcolex agglutination procedure applied to the GN indicated Salmonella spp. for 21 samples; its sensitivity was 70% and its specificity was 99% compared with GN subcultures. The Wellcolex agglutination procedure applied to the SF performed better than the agglutination of GN or direct plating procedures and detected 17 of the 39 Salmonella spp. at least 24 h earlier than did culture. PMID- 1452716 TI - Bovine humoral immune response to Cryptosporidium parvum. AB - Cryptosporidiosis is a diarrheal disease predominantly affecting cattle and humans. Sera from experimentally infected calves and calves of various ages with no histories of exposure were evaluated for immunoglobulin G to Cryptosporidium parvum. An age-associated increase in immunoglobulin G was present in experimental calves and in calves with no histories of infection from 1 to 3, but not > 3, months of age. PMID- 1452717 TI - Rapid, sensitive detection of Mycoplasma pneumoniae in simulated clinical specimens by DNA amplification. AB - The polymerase chain reaction (PCR) was investigated as a means of diagnosing Mycoplasma pneumoniae infections. The target DNA sequence was a 375-bp segment of the P1 virulence protein. This DNA segment was amplified in pure cultures of five different strains of M. pneumoniae but not in other species of Mycoplasma, Acholeplasma, or Ureaplasma that were tested. Simulated clinical specimens were used to compare PCR, culture, and the gene probe. The sensitivity of PCR was between 1 and 10 organisms. The sensitivity of culture was approximately 10(3) organisms, and the gene probe detected between 10(4) and 10(5) organisms. These results indicate that PCR has significant potential as a rapid, sensitive method for detecting M. pneumoniae in clinical specimens. PMID- 1452718 TI - Peripheral intramonocytic leishmanias in an AIDS patient. AB - Intramonocytic leishmanias were unexpectedly observed in blood smears of a Spanish AIDS patient. In immunodepressed patients from exposed countries, careful microscopic examination of blood smears should be requested by the clinician in cases of prolonged fever, and biologists must be informed that leishmanias may be fortuitously observed in the peripheral blood. PMID- 1452719 TI - Early diagnosis of toxoplasmic encephalitis in AIDS patients by dot blot hybridization analysis. AB - Central nervous system toxoplasmosis is a life-threatening infection with a mortality rate of higher than 60%. An early and rapid diagnosis is important for effective treatment of the disease. A new approach for detection of cerebral toxoplasmosis is described here. DNAs extracted from cells in cerebrospinal fluid samples (0.3 to 0.8 ml) of patients suspected of having cerebral toxoplasmosis were analyzed by a dot blot hybridization technique. A highly repetitive DNA sequence of Toxoplasma gondii (ABGTg4) was nonisotopically labelled with digoxigenin-dUTP and used as a specific DNA probe. Four of six patients analyzed gave positive signals in our hybridization assay. Two of them recovered with pyrimethamine-sulfadiazine, a drug recommended for treatment of toxoplasmosis. The other two patients with positive signals died soon after diagnosis. Patients with negative signals were found to suffer from mycobacterial infection (patient 1) or varicella-zoster virus infection (patient 6). PMID- 1452720 TI - Immunoglobulin G antibody capture enzyme-linked immunosorbent assay: a versatile assay for detection of anti-human immunodeficiency virus type 1 and 2 antibodies in body fluids. AB - In tests on specimens of dried blood, saliva, and urine from 55 human immunodeficiency virus (HIV)-seropositive and 55 HIV-seronegative patients, an immunoglobulin G capture enzyme immunoassay for the detection of antibodies to HIV types 1 and 2, GACELISA, gave 109 of 110, 109 of 109, and 109 of 110 correct results, respectively. This performance, achieved in a laboratory previously unfamiliar with the assay, suggests that GACELISA is a useful new epidemiological tool for the study of HIV infection, equally applicable to all three kinds of specimen. PMID- 1452721 TI - Aspergillus quadrilineatus, a new causative agent of fungal sinusitis. AB - Aspergillus quadrilineatus was found to be the etiologic agent of pansinusitis in a patient suffering from acute nonlymphoblastic leukemia and who had undergone allogeneic bone marrow transplantation. A. quadrilineatus was cultured from biopsy specimens of the maxillary sinus, and tissue sections with fungal stains showed a necrotic area containing dichotomously branching septate hyphae, which is morphologically consistent with Aspergillus species. The patient was successfully treated with a combination of surgical debridement, granulocyte transfusions, and intravenous administration of amphotericin B-cholesterol sulfate colloidal dispersion. This is the first report of an infection caused by A. quadrilineatus. PMID- 1452722 TI - Autoagglutination and latex particle agglutination assays. PMID- 1452723 TI - Zoonotic tuberculosis in Latin America. PMID- 1452724 TI - Bordetella pertussis versus non-L. pneumophila Legionella spp.: a continuing diagnostic challenge. PMID- 1452725 TI - The customized facemask. PMID- 1452726 TI - Potential patients are in your office. PMID- 1452727 TI - Designs and applications of palatal expansion appliances. PMID- 1452728 TI - Optiflex archwire treatment of a skeletal class III open bite. PMID- 1452729 TI - Indirect-bonded bite plate to prevent impingement on ceramic brackets. PMID- 1452730 TI - Recruitment and development of a stable orthodontic team. PMID- 1452731 TI - The post-treatment consultation. PMID- 1452733 TI - Direct bonding with light-cured adhesive precoated brackets. PMID- 1452732 TI - Space required for arch leveling. PMID- 1452734 TI - Clinical experience with direct-bonded labial retainers. PMID- 1452735 TI - Shear bond strengths of two ceramic brackets. PMID- 1452736 TI - Treatment of severe spondylolisthesis in children by reduction and L4-S4 posterior segmental hyperextension fixation. AB - Twenty children with severe lumbosacral spondylolisthesis underwent reduction, posterolateral fusion, and posterior fixation with an L4 to S2, 3, and 4 sublaminar wired rectangular rod to lessen lumbosacral kyphosis, allow early ambulation, and maintain correction. All patients had a postural deformity, 10 had preoperative neurologic findings, and 8 had severe pain. The average percentage of slip improved from 76% preoperatively to 55% postoperatively, and the slip angle improved from 25 degrees to 5 degrees (p < 0.0001). All patients had solid fusion by 6 months and no progression at 43 month follow-up on the average. We conclude that this technique reliably provides partial reduction, solid fixation, and fusion for patients with severe spondylolisthesis while allowing early ambulation. As with any spondylolisthesis reduction technique, neurologic risk should limit this procedure to well-selected patients. PMID- 1452737 TI - Ambulation after transfer of adductors, external oblique, and tensor fascia lata in myelomeningocele. AB - Forty-seven patients with myelomeningocele underwent triple (adductor, external oblique, and tensor fascia lata) transfers or double (adductor and external oblique) transfers and were retrospectively reviewed. Six patients lost significant neurologic function during the 4-years 6-month follow-up. Thirty seven of the remaining 41 patients had improved gait pattern. Seventeen required less bracing after the muscle transfers. The need for assistive devices decreased in 21 patients. Twenty-seven were able to ambulate independently postoperatively as compared with seven preoperatively. The muscle transfers are indicated in midlumbar and lowlumbar spina bifida patients to improve hip stability, control, balance, and gait pattern. PMID- 1452738 TI - Triple osteotomy of the innominate bone in treatment of developmental dysplasia of the hip. AB - Ten children (11 hips) who underwent triple innominate osteotomy between the ages of 11 and 16 years for treatment of symptomatic acetabular dysplasia and who had > 10 years of follow-up since operation were reviewed to determine if satisfactory results reported in an earlier review were maintained. The mean length of follow-up was 12 years (range 10-16 years). All hips were examined roentgenographically, and functional assessment was made with the Iowa hip scoring system. Ten of the 11 hips improved roentgenographically and eight improved functionally after operation. One hip required replacement arthroplasty 16 years after triple innominate osteotomy. PMID- 1452739 TI - Developmental hip dysplasia potentiated by inappropriate use of the Pavlik harness. AB - Nineteen patients with 28 dislocated hips treated in a Pavlik harness for > 8 weeks with no evidence of hip reduction were identified. After discontinuation of the harness use, reduction was often difficult to obtain and maintain. Thirteen of these patients (17 hips) required operative intervention to obtain stable located hips. In this group of patients, we attempted to identify factors that led to an unusually high number of failures of closed management techniques. Prolonged positioning of the dislocated hip in flexion and abduction potentiates dysplasia, particularly of the posterolateral acetabulum, and increases the difficulty of obtaining a stable closed reduction. Confirmation of satisfactory reduction during treatment with the Pavlik harness is mandatory. Such treatment should be discontinued promptly if reduction is unobtainable. PMID- 1452740 TI - Computed tomography for early evaluation of developmental dysplasia of the hip. AB - Computed tomography (CT) provides an axial image of the dysplastic hip. We reviewed 130 CT scans performed after closed reduction for developmental dysplasia of the hip (DDH) in 42 patients (52 hips). We evaluated methods of measuring CT scans and found no described measurement that was predictive of development of avascular necrosis (AVN) or persistent acetabular dysplasia. The CT scan provides an excellent image of the infant hip when the child is in a spica cast and is useful to confirm an adequate reduction. No patient in this series lost reduction after 2 weeks. PMID- 1452741 TI - Changes of blood flow of the femoral head after subtrochanteric osteotomy in Legg Perthes' disease: a serial scintigraphic study. AB - Serial quantitative scintigraphic studies using 99mTc-methylene diphosphonate were performed on 25 hips with Legg-Perthes' disease to evaluate changes in local blood flow of the femoral head after subtrochanteric varizational and/or derotational osteotomy. Studies were made preoperatively and were repeated postoperatively at 2, 4, 6, and 8 weeks at 3 and 6 months, at 1 year, and finally at 2 years after osteotomy. The relative vascularity of the affected femoral head at 2 weeks after osteotomy was significantly decreased as compared with the preoperative value. Thereafter, it increased steadily, reaching the preoperative level by 6 months with no further statistically significant increase at < or = 2 years. Our scintigraphic study showed that local blood flow of the femoral head does not increase significantly after subtrochanteric femoral osteotomy in Legg Perthes' disease. PMID- 1452742 TI - Proximal femoral osteotomy using the AO fixed-angle blade plate. AB - We describe the technique and results of proximal femoral osteotomy performed with the AO fixed-angle blade plate in 157 hips of 101 pediatric patients. Postoperative immobilization or restriction of activity was not prescribed. Fourteen complications occurred in 11 patients. Use of preoperative antibiotics decreased the rate of infection from 12% to 0%, which was significant. All osteotomies healed by 16 weeks postoperatively with no nonunions, malunions, device failures, or avascular necrosis. Using no postoperative immobilization in these children was successful and resulted in few complications when the appropriate-sized blade plate was used. PMID- 1452743 TI - Single versus double screw fixation for treatment of slipped capital femoral epiphysis: a biomechanical analysis. AB - Slipped capital femoral epiphyses (SCFE) were created in 10 pair of bovine femurs. Each pair was pinned with a single screw on one side and two screws contralaterally. The specimens were reloaded to failure. Double pin fixation yielded only a 33% increase in stiffness as compared with single pin fixation. Resistance to further slip was not proportional to screw number. The stiffness of neither double nor single screw fixation approximated that of the intact physis. Single screw fixation in slipped epiphyses is recommended because the small gains in stiffness with a second screw do not offset the risk of complications. PMID- 1452744 TI - Primary epiphyseal transplants and bone overgrowth in childhood amputations. AB - Seventeen children aged newborn to 14 years underwent major through-bone amputations or revision at our two institutions. Ten patients (group 1) had primary autogenous epiphyseal transplants taken from the amputated limb and used to cap the open medullary canal of the residual limb. Seven patients (group 2) did not have epiphyseal transplants. Nine of 10 patients in group 1 (90%) had no problems related to bone overgrowth or delay in prosthetic fitting. In group 2, six of seven patients (86%) had clinically symptomatic bony overgrowth of 20 months after the index amputation on the average. Four patients had surgical revisions. Therefore, provided healthy autogenous donor epiphyses are available, we recommend primary epiphyseal transplants to avoid the complications of bone overgrowth in childhood through-bone amputations. PMID- 1452745 TI - Bone remodeling after leg lengthening: evaluation with plain radiographs, and computed tomography and magnetic resonance imaging scans. AB - Ten patients who had undergone leg lengthening were monitored with plain radiographs and computed tomography (CT) scans at 3-month intervals. Four of them were examined with magnetic resonance imaging (MRI) scans. When the external fixator was removed, MRI scans could not demonstrate any continuous fat signals in the lengthened region, suggesting the lack of medullary cavity. CT scans disclosed double cortex in three patients and irregular new bone formation in seven. At 6 months, a medullary cavity could be detected. Other aberrations were less evident. Remodeling of new bone material required at least 1 year. PMID- 1452746 TI - Tetracycline labeling as an aid to complete excision of partial physeal arrest: a rabbit model. AB - We determined whether ultraviolet (UV) visualization of tetracycline-labeled bone allows more complete excision of experimentally created physeal arrests while minimizing required bone resection. Lateral distal femoral growth arrests were surgically created bilaterally in eight 6-week-old New Zealand white rabbits, given 3 daily oxytetracycline doses (10 mg/kg); the animals were killed 6 weeks postoperatively. Femurs were excised and dissected free of soft tissue. Ten of 16 operated femurs randomized into two groups had consistent deformity. In group I, arrest was excised with a high-speed burr without, and, in group II, with ultraviolet visualization. In group II, metaphyseal bone and calcified arrest glowed brightly, contrasting well with the epiphyseal plate. All excised specimens were examined under x 9 magnification to assess remaining bone bridges. Excision defects were filled with modeling clay, which was then removed and weighed. Thorough excision was confirmed in each specimen. Resection was easier and less bone usually was resected in the UV group (difference not statistically significant). This technique would best be used in resection of arrests involving small physes such as the distal radius, in which maximal visualization and minimal resection are essential to preserve all possible growth potential. Tetracycline labeling and intraoperative UV visualization of fluorescence allows thorough excision of partial physeal arrest while minimizing required bone resection. PMID- 1452747 TI - Meniscal cyst and magnetic resonance imaging in childhood and adolescence. AB - We retrospectively reviewed 11 cases of meniscal cyst diagnosed at the Mayo Clinic from 1976 through 1990. Patient age ranged from 4 to 18 years (average 13 years). Two cases were diagnosed on clinical findings alone. Arthrograms were available in five cases. Magnetic resonance imaging (MRI) was used in four cases. These cases illustrate the difficulty in making the diagnosis of meniscal cyst. MRI is a useful tool for diagnosing meniscal cyst and aids in surgical planning. Because of the extensive differential diagnosis of the meniscal cyst, we recommend MRI in preoperative evaluation of soft tissue masses about the knee. PMID- 1452748 TI - Physeal reconstruction with blocks of cartilage of varying developmental time. AB - Reconstruction of physeal regions excised from the distal femoral chondroepiphysis was performed in a murine model. The excised regions were replaced with analogous blocks of syngeneic tissue. Vascularity, matrix formation, and cell division were assessed as well as growth. The blocks of tissue did not produce growth consistently, although individual specimens did show some growth. Tritiated thymidine incorporation by the proliferative zone of the transplanted block of tissue was not normal. The blocks of tissue did receive a nutritional supply from the host and did continue matrix formation after transplantation. PMID- 1452749 TI - Tibial physeal changes in renal osteodystrophy: lateral Blount's disease. AB - In a group of 27 children with chronic renal failure and renal osteodystrophy, we identified eight patients with significant involvement of the proximal tibial physis (15 knees). The radiographic changes observed were analogous to those observed in tibia vara (Blount's disease) but involved the lateral physis rather than the medial physis. This observation is offered as further evidence that such changes are related to eccentric weight-bearing rather than alternative etiologies such as trauma, infection, or heredity. PMID- 1452750 TI - Brachymetatarsia of the first metatarsal treated by surgical lengthening. AB - The first metatarsal of six feet in four patients was surgically lengthened. Brachymetatarsia was caused by a congenital defect in two patients, nonunion after metatarsal osteotomy in one patient, and premature physeal closure associated with pin placement across the physis in one patient. In each patient, middiaphyseal osteotomy was performed, pins were placed into the proximal and distal metatarsal fragments, and an external distracting device was attached. After distraction, a fibular graft was inserted and the device was removed. The percentage of metatarsal length gained from the lengthening averaged 36% (range 12-68%). The fibular graft healed in the lengthened position in all patients. PMID- 1452751 TI - Neuropathic foot ulceration in patients with myelodysplasia. AB - To determine if a significant relationship existed between type of operation and eventual development of pedal skin breakdown in a spina bifida patient population, 72 feet in 36 ambulatory patients with low lumbar or sacral myelomeningocele were followed for an average of 14 years 5 months. Using a clinical classification for foot suppleness and position, we determined that foot rigidity, nonplantigrade position, and performance of surgical arthrodesis were clinical indicators that had a strong statistical relationship with eventual development of neuropathic skin changes. PMID- 1452752 TI - Supracondylar fractures of the humerus: a prospective study of percutaneous pinning. AB - In 1981, we designed a protocol to treat displaced supracondylar fractures using a modified technique of closed reduction and percutaneous pinning. After the fracture was internally fixed, intraoperative anteroposterior (AP) radiographs of each distal humerus were compared. The reduction and pinning was accepted only if the radiographs demonstrated that Baumann's angle was < or = 4 degrees of that on the normal side. Seventy-one patients had clinical and radiographic evaluations at an average of 2 years 6 months after the operation. According to Flynn's criteria, the results were satisfactory in 70 patients and unsatisfactory in one. No patient had a cubitus varus deformity at follow-up evaluation. PMID- 1452753 TI - Preliminary results of orthotic treatment of pectus deformities in children and adolescents. AB - Fifty-five children and adolescents with different types of pectus deformities and a minimum follow-up of 1 year were assessed to determine the effectiveness of nonoperative treatment with a dynamic chest compressor orthosis. Thirty-seven patients were treated and compared with 18 untreated patients. The treated patients had a better outcome. Reshaping of the contour of the chest wall was observed in 21 patients with inferior and lateral types of pectus carinatum. The dynamic chest compressor has minimal morbidity and is a valuable treatment option of pectus deformities in the growing period. PMID- 1452754 TI - Osteoarticular complications of childhood brucellosis: a study of 57 cases in Saudi Arabia. AB - Fifty-seven (36%) of a cohort of 157 children with brucellosis from Saudi Arabia had arthritis. Most gave a history of contact with farm animals or drinking unpasteurized milk. Associated features included pyrexia, arthralgia, hepatosplenomegaly, and lymphadenopathy. A subacute presentation with peripheral oligoarthritis predominantly affecting hips or knees was common. Specific chemotherapy resulted in rapid defervescence followed by slower resolution of the arthritis. Children with osteoarticular brucellosis had a higher relapse rate and a longer hospital stay. Supervised combination chemotherapy for at least 6 weeks was effective in preventing relapse. A brucellar etiology should be considered in any child from an endemic area who has osteoarticular manifestations. PMID- 1452755 TI - Long-term effects of neonatal bone and joint infection on adjacent growth plates. AB - Review of children with physeal damage from neonatal infection other than the hip at Winnipeg Children's Hospital showed that six patients had residual growth interference from adjacent infection in the bone or joint. Several of the infections involved multiple joints, with growth plate arrest occurring in the distal femoral growth plate in four, in the proximal humerus in four, in the proximal femur in two, in the distal radius in one, and in the distal humerus in one. Although the initial infection was frequently believed to be successfully treated in the neonate, the clinical effect of these infections on the growth plate was not fully appreciated in five of the infants until the children reached a mean age of 9 years. Because growth abnormalities in physeal bars may not be clinically evident for several years after the initial infection has been treated, we recommend that children with bone and joint infections occurring in the first month of life be followed to skeletal maturity, observing the adjacent physis for late tethering. PMID- 1452756 TI - Intralesional infiltration of corticosteroids in localized Langerhans' cell histiocytosis. AB - The approaches to treatment of Langerhans' cell histiocytosis (LCH) have been as varied as the clinical presentation of the disease. The clinical course of localized LCH of bone is generally benign, and it tends to heal spontaneously in a period of months to years. If treatment is required, the disease can be controlled by local measures such as surgical curettement, low-dose irradiation, or intralesional infiltration with corticosteroids. We reviewed 15 children treated with intralesional infiltration of corticosteroids, either primarily for disease of bone (8 patients) or as adjunctive therapy for disseminated LCH (7 patients). Two patients developed complications as a result of this treatment method. PMID- 1452757 TI - Post-traumatic stress disorder and coping in veterans who are seeking medical treatment. AB - The present study examined psychological coping styles and mental health treatment histories in veterans with PTSD. This study also served as a replication and extension of an earlier investigation that assessed the prevalence of PTSD in World War II, Korea, and Vietnam combat veterans who were seeking medical treatment. Thirty-six combat veteran medical patients were compared to 38 war-era controls. Nearly a third of the combat veterans met psychometric criteria for PTSD; none of the controls met these criteria. Both PTSD-positive subjects and mental health treatment seekers showed a significantly greater use of emotion-focused coping. Results also showed that Vietnam combatants were more likely to have received individual mental health treatment. These findings and their treatment implications are discussed. PMID- 1452758 TI - Are the physical and TABP risk factors for heart disease unique to CHD? AB - Scores of 40 hospitalized CHD patients on 11 Type A-related and 7 physical CHD risk factors were compared to those of 40 hospitalized non-CHD patients. Family history for CHD was the only physical risk factor for which a significant difference was found. CHD patients scored significantly higher on all seven interview-measured Type A and Type A subcomponent variables. Only two of the four Jenkins Activity Survey-measured Type A variables produced significant differences, with one higher for non-CHD subjects. It was concluded that some CHD risk scores also may be associated with other diseases, to the experience of being seriously ill, and/or to the experience of hospitalization. PMID- 1452759 TI - A comparison of 16 systems to diagnose schizophrenia. AB - Sixteen diagnostic classification systems were compared to determine the degree of agreement on the diagnosis of schizophrenia. Data were collected by a structured interview method with 284 patients, 52 first admissions, and 196 readmissions. The kappa coefficient was used to calculate interrater reliability and concordance of the systems. Adequate reliability was found for 12 of the systems. However, concordance was generally low; 11 of 120 combinations reached kappa of .40 or higher for the total sample, 16 of 120 for first admissions, and only 6 of 120 for readmissions. These results indicate the restriction of generalization and raise questions as to the empirical validity of the construct of schizophrenia. PMID- 1452760 TI - Personality predictors of bulimic behavior and attitudes in males. AB - This study was an investigation of personality factors associated with bulimic behaviors and attitudes in males. Various measures that have been noted as predictors of female bulimia were tested on 96 college students. Chronic dietary restraint and interoceptive awareness were the strongest predictors of more maladaptive eating patterns. The results suggest that maladaptive eating patterns in males and females may share a common set of features. PMID- 1452761 TI - Differentiating symptom clusters of borderline personality disorder. AB - This study is an attempt to delineate symptom clusters that may be considered most distinctive of patients diagnosed with borderline personality disorder (BPD). Medical records were examined to assess the extent to which each of the eight DSM-III-R BPD criteria was present in 89 psychiatric in-patients diagnosed with BPD. Structural analysis revealed three symptom clusters that can explain symptomatology for a majority of the sample. BPD patients can be identified initially by a core factor and separated subsequently into several BPD subtypes based on the patients' remaining symptomatology. A hierarchical diagnostic scheme for delineating BPD subtypes is proposed, and the implications of these findings for a theoretical separation of several BPD subtypes are discussed. PMID- 1452762 TI - The Missouri Children's Behavior Checklist behavioral classification system: a construct validity study with nonreferred children. AB - This study provides validity information about the Missouri Children's Behavior Checklist (MCBC) classifications system with nonreferred children. MCBC behavior patterns of 41 children were related to DSM-III symptomatology ascertained through a structured clinical interview, the Child Assessment Schedule, conducted with the mother. The findings indicated that considering the Undifferentiated Disturbance pattern as an indicator of poor adjustment may be unwarranted with nonreferred children. PMID- 1452763 TI - Do computer-administered Minnesota Multiphasic Personality Inventories underestimate booklet-based scores? AB - We ran meta-analyses that compared the Minnesota Multiphasic Personality Inventory scale scores produced in 770 booklet and 762 computer administrations described by nine studies. While most of the differences were small, the computer based scores significantly underestimated their booklet counterparts on 8 of the 13 scales. The average underestimate was about three-quarters of a T-score point and accounted for around 4% of the reliable variance. These findings suggest that separate norms and profile sheets for computer-administered MMPIs might be helpful. PMID- 1452764 TI - Depression, problem-solving ability, and problem-solving appraisals. AB - Behavioral analytic methods were used to create a college student version of the Means Ends Problem Solving Procedure (MEPS). This instrument then was administered with measures of perceived problem-solving ability to depressed and nondepressed students to determine whether differences exist in both problem solving ability and problem-solving appraisal. Analyses revealed that depressed subjects had more negative expectations and lower appraisals of their problem solving ability. However, the groups did not differ in terms of the actual quality of their behavioral solutions to interpersonal, intrapersonal, and emotional problem situations. The results are interpreted as support for the role of cognitive factors in depression and problem-solving across a range of problem solving situations. PMID- 1452765 TI - Left cerebral dominance for bilateral simultaneous sensory stimulation? AB - Hom and Reitan (1982) reported findings with respect to sensorimotor deficits in groups with lateralized cerebral lesions, but evaluated the results only within a framework that related cerebral dominance to deficits that resulted from lateralized lesions. Some of the variables they studied, however, depend upon evidence of retention of functions by one hemisphere under conditions of distracting input. While the right cerebral hemisphere appears to be dominant for tactile-perceptual abilities in terms of resulting deficits, the present study suggests that the left cerebral hemisphere is dominant for certain non-language functions that reflect maintenance of sensory-perceptual abilities under conditions of distracting stimuli. PMID- 1452766 TI - Anatomy of self-injurious, stereotypic, and aggressive movements: evidence for involuntary explanation. AB - Self-injurious movements, common in persons diagnosed with Tourette syndrome, or mental retardation, are typically difficult to eliminate. The author considers the possibility that certain self-injurious movements are involuntary phenomena. An anatomical analysis of high-frequency movements in a patient with severe head slapping is presented by tracing the muscles and nerves involved. The median nerve innervates muscles that bring the hand/arm to the head and also muscles that control this patient's other frequent movements, viz., pill-rolling, thumb gouging, wrist-flapping, and pinching the neck or cheek. Other patients underwent similar investigation: one who headbangs, one who hits out repetitively, and one with non-injurious stereotypic movements. An anatomical explanation suggests that certain self-injurious, aggressive, and stereotypic movements are involuntary muscle contractions that reflect abnormal innervation along specific nerves. PMID- 1452767 TI - The sensitivity of the Mini-Mental State Exam in the white matter dementia of multiple sclerosis. AB - Fifty-six patients diagnosed with definite multiple sclerosis (MS) according to Poser criteria were administered the Mini-Mental State Examination (MMSE) and a comprehensive battery of neuropsychological tests. Extent of cerebral lesion involvement was determined by quantitative magnetic resonance imaging (MRI) ratings. The MMSE correlated with overall levels of physical disability, but did not correlate with total lesion area on MRI. Sensitivity of the MMSE to the subcortical dementia of MS was low (28%) when performance on the neuropsychological testing battery was used as the criterion. Impairment on tests of memory, speed of information processing, abstract reasoning, naming/verbal fluency, as well as visuoperceptual organization, were correlated highly with total lesion area on MRI. The low sensitivity of the MMSE to cognitive impairment in MS is discussed in terms of its item composition and the characteristic pattern of deficits found in MS. PMID- 1452768 TI - Responsivity to cognitive therapy as a function of treatment format and client personality dimensions. AB - The effects of treatment format and client personality dimensions upon responsivity to cognitive therapy were investigated. Depressed subjects were assigned to either 12 weeks of individual or group cognitive therapy. The two formats were found to be equally effective in significantly reducing depression. Subjects were categorized at pretreatment using Beck's Sociotropy/Autonomy Scale in conducting a post hoc analysis of the impact of client personality dimensions upon responsivity to treatment. Consistent with Beck's (1983) interactional model, sociotropic subjects who received group therapy and autonomous subjects assigned to individual therapy showed greater improvement than subjects whose predominant personality dimension did not match the type of treatment received. PMID- 1452769 TI - Prescott Lecky: pioneer in consistency theory and cognitive therapy. AB - Prescott Lecky's theory of self-consistency consists of an organization of ideas that revolve around those of the self and a master motive that serves to preserve and modify the unity of ideas. Self-consistency theory anticipated several cognitive-phenomenological theories of personality and remains relevant to contemporary personality and clinical psychologists. Regrettably, Lecky left few details about the structure, processes, and development of personality. This paper first will review Lecky's career, theory, and influence. Next, the nuclear theory of the mind, attributed to Frederick Thorne, will be described. The nuclear theory refines and extends Lecky's work and will be evaluated on conceptual, empirical, and practical grounds. PMID- 1452770 TI - Correlates of suicide ideation in French-Canadian adults and adolescents: a comparison. AB - Five hundred fifty-eight French-Canadian adolescents and 150 adults served as subjects in a study that compared correlates of suicide ideation. Results of multivariate analyses indicated that suicide ideation in adolescents is related positively to depression and negative stress and negatively to self-esteem and satisfaction with social support. Adult ideation was found to be related negatively to self-esteem and positively to negative life experiences. PMID- 1452771 TI - A comparison of traditional and computer-generated psychological reports in an adolescent inpatient setting. AB - Although individual personality tests and occasionally test batteries have been the focus of considerable research, the psychological report itself has largely escaped direct scrutiny. This study examined the perceived accuracy, utility, and specificity of traditional psychological reports and compared these values with those obtained for the computer-generated report for the Millon Adolescent Personality Inventory (MAPI). Analyses indicated no difference in rated accuracy by either therapists or nursing staff. Both reports were judged as mediocre in accuracy and usefulness. The MAPI was judged to offer more specific interpretations than was the traditional psychological report and to be superior in quality of writing. A variety of substantive and extraneous variables were examined and found not to alter these results. PMID- 1452772 TI - Sadistic and self-defeating personality disorder criteria in a rural clinic sample. AB - A sample of 176 outpatients at a mental health clinic in rural southern Georgia were rated for the presence or absence of the DMS-III-R sadistic and self defeating personality disorder criteria. On the basis of these ratings, 48 patients met the criteria for sadistic (n = 14) and self-defeating (n = 41). Surprisingly, half of the patients who met the sadistic criteria also fulfilled the self-defeating criteria. A factor analysis failed to divide the criteria cleanly into sadistic and self-defeating subsets. PMID- 1452773 TI - Factors affecting the precision of warfarin treatment. AB - AIM: To determine what factors influence the precision of anticoagulant control using warfarin by examining the computerised records of 2207 patients. METHODS: Records from seven district general hospitals were combined and analysed. The precision of anticoagulant control was taken as the absolute deviation of International Normalised Ratio (INR) from target at the most recent determination. This quantity was examined using univariate and multiple regression analyses. RESULTS: Deviation of INR from target was continuously distributed, almost symmetrically about a mean of zero. The patients' age and sex had little bearing on control. Patients with a high target INR were more likely to be undertreated, and patients taking higher doses of warfarin were more likely to be overtreated. Previous over- or undertreatment were strongly related to poorer current control. The control of treatment varied substantially among the seven hospitals. One possible cause of this variation was the dose adjustment coefficient: the greater the dose adjustment for a given deviation from target INR, the better was the control achieved. CONCLUSION: Several groups of patients were identified whose control was less satisfactory and in whom anticoagulant treatment needs particular scrutiny: these include patients with a record of previous over- or undertreatment, but not elderly patients in general. The variation in control among hospitals is a source of concern that merits further attention to achieve better uniformity of anticoagulant treatment. PMID- 1452774 TI - p53 protein in odontogenic cysts: increased expression in some odontogenic keratocysts. AB - AIMS: To assess p53 protein expression in a range of odontogenic cysts arising in the mouth, including those of developmental and inflammatory origin. METHODS: p53 protein was identified using the polyclonal antibody CM-1, together with a standard immunoperoxidase technique. A total of 36 cystic lesions were examined, all of which were histologically benign. RESULTS: Expression of p53 protein was identified within the lining of five of 12 odontogenic keratocysts but was not detected in the other cystic lesions in the series. CONCLUSIONS: This is believed to be the first report that identifies increased expression of p53 protein in benign cystic epithelium. The increased expression of p53 protein in the nucleus is usually associated with malignant disease. These findings are relevant to the management of odontogenic keratocysts which have a tendency to recur, and also to Gorlin Goltz syndrome in which keratocysts and multiple basal cell carcinomas are features. PMID- 1452775 TI - p53 expression in lymphatic malignancies. AB - AIMS: To investigate the expression of p53 protein in malignant and benign lymphoid tissues. METHODS: Tissue from 42 non-Hodgkin's lymphomas, 10 Hodgkin's lymphomas, three atypical hyperplasias and five benign reactive hyperplasias was studied immunohistochemically for the expression of p53 protein. RESULTS: Of the 42 non-Hodgkin's lymphomas, 13 (31%) were positive for p53 in some of the tumour cells. In two cases the proportion of positive cells was more than 10% and in four cases it was between 1-5%. These six cases consisted of three Burkitt's lymphomas, one immunoblastic lymphoma, one centroblastic diffuse lymphoma and one angioimmunoblastic lymphoma. In seven cases the proportion of p53 positive tumour cells was less than 1%. These cases comprised three centroblastic diffuse, three centroblastic polymorphic diffuse, and one angioimmunoblastic type lymphoma. In three out of 10 (30%) Hodgkin's lymphomas, a proportion of the Reed-Sternberg cells were p53 positive. One of these was a mixed cellular subtype and two nodular sclerosing subtypes. p53 protein was not expressed in the three atypical hyperplasias or the five benign reactive hyperplasias of the lymph nodes. CONCLUSIONS: The presence of p53 positivity in non-Hodgkin's and Hodgkin's lymphomas indicates that mutations of the p53 gene may play a part in the development of these tumours. The concentration of p53 positivity in high grade lymphomas suggests that p53 is involved in the transformation of low grade lymphomas to more aggressive types. Because no p53 positivity was observed in benign lesions of the lymph nodes, positive p53 immunohistochemical staining in a lymphoid lesion suggests malignancy. PMID- 1452776 TI - Intramammary lymph nodes. AB - AIMS: To determine the prevalence and pathology of intramammary lymph nodes in breast specimens. METHODS: All breast specimens examined by a single pathologist over 70 months in a large teaching hospital were studied retrospectively. All the surgical pathology reports were reviewed. Relevant glass slides from cases in which intramammary lymph nodes were identified were also reexamined. RESULTS: Breast specimens (n = 682) were examined. Seven lymph nodes were found in five patients. The specimens comprised 533 biopsy specimens, 29 segmental resections, 22 reduction mammoplasties, 77 modified radical mastectomies and 20 gynecomastia mastectomies. No clinically relevant microscopical abnormalities were found in four lymph nodes and slight sinus histiocytosis was seen in two nodes. One node contained metastatic adenocarcinoma and benign glandular epithelial inclusions. CONCLUSION: Although rare, intramammary lymph nodes may be detected by careful gross examination of breast specimens even in the absence of clinical identification. They can occur in any quadrant of the breast and can display a variety of pathological conditions. Pathologists should be alert to the existence and potential importance of these lymph nodes. PMID- 1452777 TI - Immunohistological study of distribution of gamma/delta lymphocytes after allogeneic bone marrow transplantation. AB - The distribution of T lymphocytes expressing the gamma/delta form of the T cell receptor was studied in the liver, intestine, and major lymphoid organs, after bone marrow transplantation (BMT), including cases of graft versus host disease (GvHD). The number of gamma/delta as a proportion of the total number of CD3 positive cells did not differ from that found in normal tissues; the higher percentage normally found in the intestinal epithelium and splenic red pulp was maintained. This, and the results of a previous study undertaken on the skin, provide no evidence that gamma/delta T cells have a particularly important role in T cell regeneration after marrow transplantation or in the pathogenesis of the epithelial lesions associated with GvHD. PMID- 1452778 TI - Well differentiated (benign) papillary mesothelioma of the tunica vaginalis. AB - An unusual mesothelial lesion occurred in the tunica vaginalis of the testis. It conformed histologically and immunohistochemically to well differentiated papillary mesothelioma of the peritoneum. Its aetiology remains uncertain, but this lesion, more than likely, is innocuous. It is important to recognise this entity, which is not well documented in the tunica vaginalis, because it may be misdiagnosed as a malignant mesothelioma and the patient may be subjected to unnecessary treatment. PMID- 1452779 TI - Mucous metaplasia of the pleura. AB - A case of mucous metaplasia of mesothelium in an 80 year old woman is described. Its cause is unknown, but it is important not to confuse it with secondary tumour. PMID- 1452780 TI - Intradural bronchogenic cysts. AB - The pathological findings of an intradural and extramedullary cyst in the mid cervical spinal canal are described in a 55 year old woman who presented with a short history of pain and paraesthesia of the right arm. Intradural well defined solitary cystic lesions in the spinal canal are uncommon, their pathogenesis is poorly understood, and their nomenclature is confusing. In this case the cyst was a bronchogenic cyst; these are a rare form of such cysts and they are thought to be a malformation arising from a split notochordal syndrome and not a teratoma. PMID- 1452781 TI - Pneumococcal endocarditis and disseminated infection. AB - A 61 year old woman presented with back pain and clinical signs of meningitis. Pleocytosis in the cerebrospinal fluid was found, but although Streptococcus pneumoniae was cultured from her blood it failed to grow from the cerebrospinal fluid. An echocardiogram detected vegetations on the mitral valve and a lesion at S1/S2 was demonstrated on a bone scan. Treatment for one month with benzylpenicillin (1200 mg four hourly) was successful for both the cardiac and neurological components of her infection, but her back pain only resolved after treatment was changed to clindamycin. The clinical presentation and metastatic spread of the S pneumoniae infection is much more commonly seen in the context of S aureus endocarditis. It is rare for the pneumococcus to be associated with endocarditis and when it is mortality is usually high. This case shows the metastatic potential of the organism and the requirement for appropriate antibiotics with regard not only to the sensitivity of the organism, but also for the site of infection. PMID- 1452782 TI - Screening for Corynebacterium diphtheriae. AB - A throat swab from a 9 year old girl with pharyngitis yielded a non-toxigenic strain of Corynebacterium diphtheriae var mitis and Streptococcus group G. C pseudodiphtheriticum was isolated from the throats of two of her four brothers. In each case the isolate was sent to the reference laboratory before full identification. The growth was found to be mixed for one brother; the other isolate being a toxin producing C diphtheriae var gravis. The child was asymptomatic and the case proves that all colonial types on the Hoyles plate should be identified. PMID- 1452783 TI - Chronic giardiasis of the stomach. AB - Two cases of chronic giardiasis of the stomach diagnosed from gastric mucosal biopsy specimens are reported. The first case was associated with an acute-on chronic gastritis and Helicobacter-like organisms, and the second with an adenocarcinoma of the stomach. In both cases the trophozoites had been missed in earlier biopsy specimens. As far as is known this is the first report of giardiasis of the stomach. PMID- 1452784 TI - Restrictive endocardial fibroelastosis in a neonate without other cardiac pathology. AB - A case is presented of constrictive endocardial fibroelastosis without other cardiac abnormality in a newborn infant who was treated successfully by orthotopic heart transplantation. PMID- 1452785 TI - Changing trends in infective endocarditis. PMID- 1452786 TI - Safety in the laboratory. PMID- 1452787 TI - ACP Broadsheet 133: November 1992. Gross examination of the stomach. PMID- 1452788 TI - New rapid identification test for Clostridium difficile. AB - AIMS: A set of five tests were developed and tested for their ability to confirm the identity of C difficile colonies within 30 minutes. METHODS: The relevant substrates were incorporated into four filter paper squares attached to a plastic carrier (Diffstrip), five enzymes/products (prolyl aminopeptidase, galactosidase, leucine aminopeptidase, acid phosphatase and indole). The strips were inoculated, incubated for 20 minutes, and reagents added. RESULTS: 96.4% (212 of 220) strains of C difficile were immediately differentiated from 51 other Clostridium spp tested. The remaining 3.6% (eight of 220) of C difficile isolates produced a reaction pattern similar to some of the Clostridium sporogenes tested and required additional tests. None of the other Clostridium spp tested produced reaction patterns similar to C difficile. CONCLUSION: The Diffstrip allowed colonies of C difficile to be confirmed within 30 minutes for 96.4% of isolates, with less than 4% requiring any additional tests. No strains of C difficile were misidentified and no strains of other Clostridium spp tested were misidentified as C difficile. PMID- 1452789 TI - Aeromonas spp as a potential cause of diarrhoea in children. AB - AIMS: To determine the prevalence of Aeromonas spp in the faeces of children and the association with symptoms of gastroenteritis. METHODS: Faecal specimens (n = 1026) were cultured for Aeromonas spp using three selective media and an enrichment broth at both 30 degrees C and 37 degrees C. The isolation of Aeromonas spp was correlated with symptoms of gastroenteritis, previous antibiotic use, and environmental temperature. RESULTS: Aeromonas spp (n = 28) from 26 (2.5%) patients were recovered. Bile salt, Irgasan, and brilliant green agar was the most efficient selective culture medium. Eleven of the patients had symptoms of gastroenteritis, usually mild diarrhoea of two to three days' duration, in the absence of other recognised enteropathogens. A caviae was a particularly frequent isolate (nine out of 11 cases) in symptomatic individuals. Only one out of seven Aeromonas spp recovered by enrichment culture alone was possibly associated with symptoms of gastroenteritis. There was a close correlation between the environmental temperature and isolation of Aeromonas spp. CONCLUSIONS: Aeromonas spp and particularly A caviae may cause gastroenteritis in children, most often during warmer months of the year. Culture for these potential enteropathogens could be confined to summer and autumn months. Bile salt, Irgasan, and brilliant green selective agar, but not alkaline peptone water enrichment, is an efficient culture medium for recovering possibly clinically important isolates. PMID- 1452790 TI - Gastric giardiasis. AB - AIMS: To assess the prevalence of gastric giardiasis in patients undergoing upper gastrointestinal endoscopy, and to define the clinicopathological correlates of gastric Giardia lamblia infection. METHODS: Consecutive gastric biopsy specimens (n = 15,023) from 11,085 patients, taken at Feltre City Hospital (north eastern Italy) from January 1986 to December 1991, were histologically and immunocytochemically examined for the occurrence of G lamblia trophozoites. Three gastric biopsy specimens from patients harbouring G lamblia infection, who repeated endoscopy before treatment, were also examined electron microscopically. RESULTS: Forty one patients (0.37% of the population study) harboured gastric giardiasis. All patients underwent upper gastrointestinal endoscopy because of dyspepsia, epigastric pain, or abdominal distension. Only two patients had diarrhoea at the time of investigation. Giardiasis was clinically unsuspected in all cases, although the nine patients who also had duodenal biopsies performed had concomitant intestinal giardiasis. Gastric giardiasis was invariably associated with chronic atrophic gastritis. Intestinal metaplasia of the gastric mucosa and Helicobacter pylori infection were found in 32 and 37 of the 41 patients with gastric giardiasis, respectively. CONCLUSIONS: The invariable association of gastric giardiasis with chronic atrophic gastritis, most often showing intestinal metaplasia and H pylori infection, indicates that a decreased gastric acidity is a prerequisite for localisation of G lamblia to the gastric mucosa. Though its possible role as a gastric pathogen remains to be elucidated, these findings suggest that trophozoites should be carefully searched for when examining gastric biopsy specimens showing chronic atrophic gastritis. PMID- 1452791 TI - Parasitology: United Kingdom National Quality Assessment Scheme. AB - AIMS: To assess the results from parasitology laboratories taking part in a quality assessment scheme between 1986 and 1991; and to compare performance with repeat specimens. METHODS: Quality assessment of blood parasitology, including tissue parasites (n = 444; 358 UK, 86 overseas), and faecal parasitology, including extra-intestinal parasites (n = 205; 141 UK, 64 overseas), was performed. RESULTS: Overall, the standard of performance was poor. A questionnaire distributed to participants showed that a wide range of methods was used, some of which were considered inadequate to achieve reliable results. Teaching material was distributed to participants from time to time in an attempt to improve standards. CONCLUSIONS: Since the closure of the IMLS fellowship course in 1972, fewer opportunities for specialised training in parasitology are available: more training is needed. Poor performance in the detection of malarial parasites is mainly attributable to incorrect speciation, misidentification, and lack of equipment such as an eyepiece graticule. PMID- 1452792 TI - Solitary necrotic nodule of the liver: parasitic origin? AB - AIMS: To report further cases of solitary necrotic nodule of the liver and to study its nature. METHODS: Seven nodules were retrieved from 4000 necropsy and surgical liver specimens coming to light over the past five years. All of them satisfied the diagnostic criteria of solitary necrotic nodule: a solid lesion with a central necrotic core and a hyalinised fibrotic capsule containing elastic fibres. Their clinicopathological features were reviewed. RESULTS: The nodules were incidental findings at surgery or necropsy in four men and three women whose ages ranged from 48 to 79 years (mean 63.7 years). Four were found in the right lobe and three in the left. Six were subcapsular and only one deep in the parenchyma, with sizes ranging from 0.3-2.5 cm. Each of them was solitary, well demarcated, and round to oval with a firm, whitish rim and a core of yellowish white cheese-like to solid material. In addition to the basic architecture, there were a number of common and undescribed histological features: presence of varying numbers of small mural vessels with intimal fibrosis and obliteration, presence of cholesterol clefts and foamy cells among necrotic material, and sparsity of inflammatory cells. In the two cases where ghosts of degenerated cells and partially preserved liver reticulin pattern were noted, worms were identified, one being Clonorchis sinensis. CONCLUSIONS: The entity is believed to be a "burnt-out phase" of a variety of benign lesions. Parasitic infestation is another possible cause, and presence of ghosts of degenerate cells, partially preserved liver reticulin pattern, cholesterol clefts and foamy cells among necrotic material are auxiliary features pointing to such an aetiology. The variation in morphological fine details reflects both the lesion's diverse pathogenesis and the fact that it can be of varying duration. PMID- 1452793 TI - Effects of chemotherapy on ultrastructure of oesophageal adenocarcinoma. AB - AIMS: To compare and contrast the ultrastructural appearance of resected oesophageal adenocarcinomas treated with preoperative chemotherapy with that of non-treated resected controls; and to determine the usefulness of this method in the assessment of the effectiveness of the chemotherapeutic regimen. METHODS: Ten resected oesophageal adenocarcinomas treated with preoperative chemotherapy- mitomycin-C, ifosfamide, and cisplatin (MIC)--were examined by transmission electron microscopy and their appearance compared with that of 13 concurrent untreated resected oesophageal adenocarcinomas. RESULTS: The treated adenocarcinomas showed cytotoxic damage although complete tumour eradication was not achieved. In all 10 treated cases a variable proportion of the neoplastic cells showed unusual degenerative and necrotic changes not seen in untreated cases. In the most affected carcinomas the stroma contained increased numbers of inflammatory cells. CONCLUSIONS: This ultrastructural method is useful for the assessment of the in vivo effect of MIC. PMID- 1452794 TI - Histopathological and microanalytical study of zirconium dioxide and barium sulphate in bone cement. AB - AIMS: To report the appearances of zirconium dioxide and barium sulphate in interface membranes, synovium, and other tissues around joint prostheses. METHODS: Histological sections from 23 specimens were reviewed by light microscopy and polarisation. Scanning electron microscopy and x ray microanalysis were performed on routinely processed paraffin wax sections. RESULTS: Polyethylene, metals, and polymethylmethacrylate cement debris were easily recognisable. Almost all the cement remnants contained either zirconium dioxide or barium sulphate, confirmed by microanalysis. The contrast media had characteristic light microscopic appearances. Zirconium was identified in macrophages away from cement remnants. CONCLUSION: The presence of radiographic contrast media in tissues around prosthetic joints is common but not widely recognised. PMID- 1452795 TI - Remodelling of subchondral bone in osteoarthritis: a histomorphometric study. AB - AIMS: To determine whether remodelling of subchondral bone in osteoarthritis is related to anatomical and mechanical factors operating on the joint surface. METHODS: Ten femoral heads were examined. Patients due to have the femoral head removed because of osteoarthritis were given a double tetracycline label before surgery. The specimens were divided in three roughly equal parts, corresponding to the medial, central (weight bearing), and lateral aspects of the femoral heads. Undecalcified methylmethacrylate embedded sections were prepared. The subchondral bone was assessed for appositional bone formation by ultraviolet light microscopy, for resorptive activity by osteoclast count, and for trabecular bone volume by semiautomatic computerised image analysis. Appositional bone rate was also correlated with the presence or absence of overlying cartilage. RESULTS: Bone density was reduced in the medial aspect of the femoral heads but there was no significant difference between the appositional bone rate or the resorptive activity in the three areas. Nor was there any correlation between appositional bone rate in the subchondral bone and the presence or absence of overlying cartilage. CONCLUSION: Remodelling of subchondral bone in osteoarthritis, at least in the short term, is fairly constant and is not related to weight bearing. PMID- 1452796 TI - Chronic transmural bronchiolitis: a non-specific lesion of small airways. AB - AIMS: To investigate nine patients with histological changes at open lung biopsy compatible with so-called "small airways disease"; to define these changes and distinguish them from other types of bronchiolitis; and to correlate them with clinical features, respiratory physiology, and other laboratory investigations. METHODS: The open biopsy sections and the clinical records were reviewed. RESULTS: There was chronic inflammation of the walls of centri-acinar respiratory bronchioles and peribronchiolar alveoli. Peripheral alveoli of affected acini were spared. Although lumens were narrowed and distorted, obstruction by granulation tissue plugs was not a feature. Clinical backgrounds included Hodgkin's disease, yellow nail syndrome, sicca syndrome, asthma and psoriasis. The main presenting symptoms were cough, dyspnoea and wheeze, often associated with basal crackles and basal shadowing. There was no consistent immunological or haematological abnormality. Sputum culture was negative in six patients, and a variety of organisms were cultured from three others. In most cases respiratory function tests revealed an irreversible obstructive defect (combined in some cases with a restrictive defect), gas trapping, and well preserved gas transfer. Lung volumes were normal. Bronchodilators, with steroids and azathioprine in more seriously affected patients, stabilised the disease process. CONCLUSIONS: The histological changes may be distinguished from bronchiolitis obliterans and bronchiolitis obliterans organising pneumonia by the absence of intraluminal granulation tissue plugs, and from the obliterative bronchiolitis of rheumatoid disease and diffuse peribronchiolitis on clinical grounds. Although often striking, this lesion does not represent a clinico-pathological entity, and may occur in the distal lung in association with a number of different diseases. "Small airways disease" is often used by clinicians in a functional context, and may lead to confusion. It is suggested that "chronic transmural bronchiolitis" is a more appropriate term. PMID- 1452797 TI - The effect of strontium chloride hexahydrate dentifrices on plaque accumulation and gingival inflammation. AB - 2 strontium chloride hexahydrate-containing dentifrices (SCH), similar except for their respective abrasive systems, diatomaceous earth or silica-based, were compared for their effects on plaque accumulation and gingival inflammation as part of a 2-month randomised double-blind parallel clinical study. No attempt was made to change the patients' oral hygiene prior to participation in the study. Plaque was assessed using the Silness & Loe index and the gingival condition by the Loe & Silness index GI. There was a slight and non-significant increase in plaque accumulation at 2 weeks from baseline, but relatively negligible change thereafter, the effect being identical in both groups. Similarly, the gingival condition showed a slight index change from baseline, although it tended to be slightly higher in the diatomaceous earth group. The results do not support the conclusions of previous studies which indicated that SCH dentifrices increased plaque accumulation. Neither plaque accumulation nor gingival condition significantly changed from baseline levels during the course of the study. PMID- 1452798 TI - Mineralized tissue-formation in periodontal wound healing. AB - The purpose of the present study was to examine and compare the different mineralized tissues that are found on and around the dental root following treatment of different periodontal pathosis. The material has been compiled from previously published experimental studies on periodontal therapies and trauma treatments. 4 distinctly different appearances of the mineralized tissue layers on the marginal dentin surfaces were described; new cementum, non-attached bone like tissue, partly attached bone-like tissue and ankylosis preceded by root resorption. It was concluded that, healing in the periodontal/root interface following periodontal therapy may yield different mineralized tissues, depending on a number of host-specific and external factors. The temporal pattern of such healing processes is schematically represented. PMID- 1452799 TI - A comparison of delmopinol and chlorhexidine on plaque regrowth over a 4-day period and salivary bacterial counts. AB - Delmopinol has been considered as a potential agent for the chemical control of plaque. The aims of these studies were to measure the effects of a 0.2% delmopinol hydrochloride mouthrinse on (1) plaque reformation and (2) salivary bacterial counts. Comparisons were made with a 0.2% chlorhexidine rinse and a placebo rinse. A group of 12 male volunteers took part in the plaque study which was of a double blind, randomised, 3 cell, cross-over design. From a zero plaque baseline subjects rinsed, 2x a day, under supervision, for 1 min with 10-ml volumes of the allocated rinse. After 4 days, during which no other form of oral hygiene was performed, plaque was scored by area and index. Plaque results were significantly lower with chlorhexidine and delmopinol compared with control, and with chlorhexidine compared to delmopinol. Side-effects with delmopinol were transient tingling and numbness of the tongue in some subjects. A 2nd group of 12 male volunteers received single, 1-min rinses of the 3 formulations. Salivary bacterial counts were determined immediately before and up to 420 min after rinsing. Compared to the control rinse, chlorhexidine significantly reduced bacterial counts of 420 min. Delmopinol produced a small reduction in bacterial counts which was only significantly different from control at one time point. Delmopinol deserves further evaluation as a chemical plaque inhibitor, particularly when used as an adjunct to normal toothcleaning. PMID- 1452800 TI - Probing pocket depth at mobile/nonmobile teeth. AB - The aim of the present investigation was to study the influence of an increased tooth mobility on the resistance offered by the periodontal tissues to probing. 6 beagle dogs were used. At the start of the experiment, the animals had clean teeth and normal gingival and periodontal conditions. In each dog, a device was installed in the lower left jaw quadrant to expose the third premolar (P3) to jiggling forces which would enhance the mobility of this "test" tooth. The contralateral tooth served as the non-jiggled control. During the 3 months of experimentation, the teeth of the dogs were cleaned on a regular basis. Clinical examinations including tooth mobility measurements were performed on days 0 and 90. After the examination on Day 90, a probe was inserted in the buccal "pocket" of the mesial root of 3P and P3. The probe was retained with composite. Biopsies including the test or control tooth with adjacent buccal periodontal tissues were harvested, fixed and decalcified. Each biopsy was divided in one mesial and one distal portion (root). The distal portion was embedded in Epon, sectioned and stained in PAS and toluidine blue, while the mesial portion, following probe removal was embedded in paraffin, sectioned and stained in hematoxylin-eosin. The sections were exposed to histometric and morphometric measurements. The findings demonstrated that tissue alterations which occur at mobile teeth may reduce the resistance offered by the periodontal tissues to clinical probing. Such alterations include (i) reduced height of the alveolar bone, (ii) reduced amount of collagen, and increased vascularity in the enlarged supracrestal connective tissue. PMID- 1452801 TI - The effect of supragingival plaque control on the composition of the subgingival flora in periodontal pockets. AB - The effect of mechanical supragingival plaque control on the composition of the subgingival microflora in untreated 4-6 mm deep periodontal pockets was investigated. 13 subjects with chronic periodontitis were recruited for the study. Periodontally-diseased sites were subjected to professional plaque control 3 x weekly for a period of 3 weeks. Contralateral sites received no prophylaxis and served as controls. No instructions in oral hygiene procedures were given to the patients who maintained their habitual oral hygiene regime during the observation period. Clinical examination and darkfield microscopic analysis of bacterial samples were performed every week. The PlI scores for the experimental sites were reduced markedly, while those for the control sites remained stable throughout the observation period. No changes in the other clinical parameters were detected during the study. The composition of the subgingival microflora at the control sites did not change during the experimental period. In contrast, at the test sites, the proportion of spirochetes+motile rods decreased continuously. This decrease reached statistical significance at the end of the experiment. The results indicate that at periodontally diseased sites with an established subgingival ecosystem, supragingival plaque removal may influence the composition of the subgingival microflora. PMID- 1452802 TI - Guided tissue regeneration in the treatment of infrabony defects on maxillary premolars. A pilot study. AB - The present study evaluated clinically and radiographically the short-term results of the healing of infrabony defects at maxillary premolars treated according to guided tissue regeneration (GTR). 9 patients with bilateral presence of infrabony defects with or without furcation involvements at maxillary premolars were selected. At baseline assessments of plaque and gingival indices, bleeding, probing pocket depth and attachment level, and furcation measurements were recorded. Conventional radiographs were obtained in a way that assured a reproducible projection geometry. One premolar was randomly treated with GTR and the contralateral with open debridement. Clinical and radiographic examinations were performed again 6 months postoperatively. The bone tissue changes were assessed by means of conventional radiographs and subtraction images. Sites treated by both procedures demonstrated an improvement of gingival conditions and a reduction of pocket depths. A statistically significant attachment gain was obtained for the test (mean 1.2 mm), but not for the control sites (mean 0.6 mm). The differences, though, were not significant between the test and control sites. Limited improvement in furcation closure was recorded. The radiographic examination demonstrated loss of bone tissue in four sites treated with GTR. The findings suggest that the regeneration of the periodontal soft and bone tissues was not significantly enhanced with the GTR therapy. PMID- 1452803 TI - Intrafamily influences on health behavior. A study of interdental cleaning behavior. AB - The purpose of this study was to assess quantified measures of intrafamily patterns of influence on interdental cleaning behavior based on a conceptual model of family influences on health behavior. Data stemmed from the Norwegian National Health Survey 1985, comprising 295 two-parent families with 2 children above 6 years of age. Analyses were performed with the family as the sampling unit. Logistic regression analyses were applied. The results showed that there were statistically significant associations of interdental cleaning behavior among all pairs of family members, the strongest association being between sibling (OR = 36.6). The multivariate analyses of interdental cleaning behavior of the children showed that the strongest explanatory factor was the interdental cleaning behavior of the mother (OR = 2.4). Thus, the mother seems to play an important role in the formation and maintenance of the elder child's interdental cleaning behavior. The highly correlated interdental cleaning behavior of the 2 siblings could be explained by correlated measurement errors as well as equity in rules and parental control and reinforcement of the behavior, in addition to substantive influential effect of the elder sibling's interdental cleaning behavior on that of the younger sibling. PMID- 1452804 TI - The power of tests to detect differences between periodontal treatments in published studies. AB - 10 studies comparing periodontal treatment modalities were re-examined to see if they had adequate power to detect true differences. Attachment level (AL) and pocket depth (PD) were the 2 variables assessed. A statistical test's power refers to its probability of detecting a significant sample difference in treatment means, given a predetermined value for alpha (level of significance), delta (a clinically meaningful underlying difference), and the sample size. Studies were included that stratified their data by initial pocket depths, reported sample size, and lasted at least 6 months. Power calculations were done for 173 treatment comparisons, using delta = 0.5 mm and alpha = 0.05. For shallow pockets (1-3 mm), most studies had a strong chance of detecting true differences (median power = 83%). For moderate pockets (4-6 mm), median power dropped to 38%. However, median power dropped to 14% for deep pockets (> 6 mm), with 75% of the tests having less than a 20% chance of detecting a 0.5 mm difference. Many of the modalities reported as "not significantly different" from each other have not had a fair trial, especially for deep pockets. In order to improve a study's power, 4 factors are discussed: the number of compared treatments, the expected noise or random error, the patient sample size, and the average number of sites per patient for each pocket depth category. PMID- 1452805 TI - Crossover trials comparing several treatments. AB - Designs exist for crossover studies in which the possibility of distortion by carryover effects is minimised. A novel design including 5 treatments and 15 subjects with this property is presented, along with existing designs. These designs incorporating balance for carryover effects should be used in preference to cyclical permutation designs. Statistical analysis of the resulting data is readily performed. PMID- 1452806 TI - Patient preference regarding 4 types of periodontal therapy following 3 years of maintenance follow-up. AB - It has been shown that certain types of periodontal therapy result in greater post-therapy gingival recession. It has been suggested that this recession may lead to maintenance complications for patients. This study evaluated patient perceptions 3 years following the completion of 4 types of periodontal therapy (coronal scaling (CS), root planing (RP), modified Widman surgery (MW), and flap with osseous resectional surgery (FO)). 75 individuals completed split-mouth therapy and 3 years of maintenance follow-up. An interview survey of all patients categorized their perception for each treatment of their mouth concerning difficulty in cleaning, sensitivity to temperature, general "feeling" of the region, prevalence of localized symptoms, food retention, comfort of oral examination, and attitude toward repeating therapy. Responses to questions showed no statistically significant differences between treatment regions. Patterns demonstrated that FO-treated regions were perceived to have less food retention, but were more difficult to clean. It was generally found that at the end of 3 years of maintenance, patients felt their mouths were "normal", they experienced few localized symptoms, and were very willing to repeat any of the treatment regimens if necessary. PMID- 1452807 TI - Periodontal changes by HIV serostatus in a cohort of homosexual and bisexual men. AB - These data represent 20 months of follow-up on 114 homo/bisexual men. Periodontal changes were analyzed in relation to HIV-1 serostatus, immune status, age and plaque. Gingival index (GI), plaque index (PI), and relative attachment levels recorded by the computerized Florida disk probe were performed every 4 months. A threshold of > or = 3.0 mm of relative attachment loss (RAL) was selected as a significant longitudinal change. RAL > or = 3 mm occurred 6.16 times (95% CI = 1.95, 19.40) more frequently among subjects with T4 counts < 200 compared to subjects with counts of 200 or more. Among older subjects (age > or = 35 years), the incidence (33%) of RAL > or = 3 mm was significantly higher (p = 0.004) in more immunosuppressed subjects (T4 < 200) compared to the incidence (5%) in less immunosuppressed subjects (T4 > or = 200); this association was not significant in younger subjects less than 35 years old (p = 0.55). In 78 subjects present at all follow-up visits, averaged GI increased and were significantly higher in the seropositive subjects compared to seronegative subjects, but, GI was not related to T4 cell counts within the seropositive group. Separate linear regression of GI by PI by HIV serostatus revealed a significantly higher slope in the seropositive group compared to the seronegative group (p = 0.04), suggesting greater sensitivity to plaque in the seropositive group. CONCLUSION: immunosuppression, especially in combination with older age, may be a risk factor for attachment loss, and HIV seropositivity, independent of T4 cell counts, may be a risk factor for gingival inflammation. PMID- 1452808 TI - The effect of supragingival plaque control on the subgingival microbiota in subjects with periodontal disease. AB - The present investigation was performed to study the effect on the subgingival microbiota, of a plaque control program which included meticulous oral hygiene instruction, supragingival scaling and professional monitoring during a 2 year period. 300 subjects were examined for periodontal disease and monitored for 2 years without treatment. After the 2 year examination, 80 subjects were invited to participate in a treatment program intended to improve the standard of their self-performed plaque control. 40 of the invitees had a gingivitis and only minor attachment loss, while 40 subjects had moderate signs of periodontitis. 62 subjects volunteered for this treatment. 23 of the volunteers (Group AB) had several sites with deep pockets (> 4 mm). 39 of the volunteers had gingivitis but shallow pockets only (Group C). Group AB contributed 31 shallow pocket sites (A sites) and 40 deep pocket sites (B-sites), while Group C contributed 63 shallow sites (C-sites). After the clinical examination, samples of the subgingival microbiota were harvested from the 134 A, B and C sites. The 62 subjects were enrolled in a supervised oral hygiene program. Supragingival scaling was carried out. Oral hygiene instruction was provided and repeated on an individual need basis so that all subjects reached and maintained a supragingival plaque score which was < 20%. 24 months after the year 2 examination, the 62 subjects were examined again using both clinical and microbiological examination procedures. The findings demonstrated that carefully performed supragingival plaque control changed the quantity and the composition of the supragingival microbiota.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452809 TI - A survey and review of hepatobiliary lesions in Australian macropods. AB - This report presents information on the range of diseases and lesions that occurred in sections of livers of macropods held in the Non-Domestic Animal Registry at Taronga Zoo. Of 142 affected livers, 52 were due to parasites, 24 to bacteria, nine to Macropod Herpesvirus, four to fungal agents and ten to tumours. In addition, 17 livers had acute degenerative or necrotic lesions, 22 were affected by fibrosis or other chronic lesions and four had miscellaneous degenerative lesions. Common parasitic diseases included toxoplasmosis, coccidial cholangitis, cestode cholangitis (Progamotaenia sp.), fascioliasis and capillarial hepatitis. Bacterial diseases were varied but lesions due to anaerobic bacteria or Mycobacteria spp. were most common. Many of the acute degenerative lesions were associated with cardio-respiratory disease. Chronic lesions were often of unknown origin, although it was speculated that parasitic and bacterial organisms contributed to the aetiology. There were four primary and six metastatic tumours. PMID- 1452810 TI - Peripheral neuropathy in German shepherd dogs. AB - Three aged (10-year-old) German Shepherd Dog litter mates, separately reared, were affected with familial and adult onset peripheral neuropathy. They developed clinical signs, unsteady gait of their hind legs with progressive muscular weakness at almost the same time. The main lesions were systemic neurogenic muscular atrophy, segmental demyelination and Wallerian degeneration of the peripheral nerve fibres. Histochemically, collateral ramification and multiple terminal arborization were observed in terminal axons of motor neurones in the muscles. These changes were attributed to a dying-back process. PMID- 1452811 TI - Immunofluorescent antibody response to lactic dehydrogenase virus in different strains of mice. AB - The development of antibody against lactic dehydrogenase virus in five strains of mice (NZB x NZWF1, BALB/c, C.B-17, ICR and C.B-17 scid or SCID mice) was examined by indirect immunofluorescence (IIF) of infected liver sections. IIF antibody appeared 1 to 3 weeks and rose progressively 2 to 4 weeks after infection in four strains of mice (NZB x NZWF1, BALB/c, C.B-17 and ICR mice). SCID mice did not develop antibody. These results suggest that IIF may be applicable for detecting LDV infection in many other ordinary strains of mice. PMID- 1452812 TI - Histochemistry of glandular metaplasia at the trigone of the urinary bladder in cows. AB - The epithelium at the trigone of the urinary bladder showed intestinal metaplasia of a colonic type in three Holstein-Friesian cows affected with chronic polypoid cystitis. Except for Ricinus communis (RCA-I), almost all goblet cells in the whole crypt were positive to periodic acid-Schiff (PAS), alcian blue (AB) pH 2.5, AB pH 1.0, periodate borohydride-potassium hydroxide-PAS (PB-KOH-PAS), Ulex europaeus (UEA-I), Triticum vulgare (WGA) and Arachis hypogaea (PNA) after neuraminidase digestion. This result indicated that most goblet cells contained acidic and neutral glycoconjugates as O-acetylated sialomucin, L-fucose, N-acetyl glucosamine, neuraminic acid residues and sialic acid-galactose dimers and were devoid of beta-D-galactose. The goblet cells at the surface in the upper half of the crypt contained both sulpho- and sialo-mucins with N-acetyl-galactosamine residues by AB (pH 2.5)-PAS, high iron diamine (HID)-AB (pH 2.5), Dolichos biflorus (DBA) and Glycine maximus (SBA) reactions. On the other hand, the lower goblet cells were found to contain predominantly sulphated mucins with D-mannose and D-glucose residues by AB-PAS, HID-AB and Concanavalia ensiformis (Con A) reactivities. This suggested that mucin secreted from these cells was similar to that secreted from the goblet cells of the large intestine in cattle. PMID- 1452813 TI - A pathological study of bovine alimentary mycosis. AB - A 10-year study showed that 45 of 692 cattle aged > 6 months had systemic mycosis and, of these, 38 had alimentary mycosis. The percentages of these 38 cattle with lesions in various sites were: rumen (73.7), omasum (71.1), abomasum (34.2), reticulum (21.1), intestine (15.8), omasoabomasal orifice (7.9) and tongue (2.6). Infections in both the forestomachs and abomasum occurred in 31.6 per cent; mucormycosis was found in 94.7 per cent and aspergillosis in 31.6 per cent; 26.3 per cent (10 cattle) had complicated infections with both Mucorales and Aspergillus and eight of these animals had mixed lesions of both mucormycosis and aspergillosis. Macroscopically, focal haemorrhagic necrosis was seen in all 38 cattle. Histologically, thrombosis, coagulative necrosis and hyphae typical of the order Mucorales or of Aspergillus spp. were found. Many of the cattle were also affected by ruminal acidosis-inducing factors (ruminal atony 81.6 per cent, mastitis 63.2 per cent, "downer cow syndrome" 57.9 per cent and parturition 50.0 per cent), which may have predisposed to alimentary mycosis. PMID- 1452814 TI - An epidemic of toxoplasmosis in a captive colony of squirrel monkeys (Saimiri sciureus). AB - An epidemic of acute, disseminated toxoplasmosis caused 30 per cent mortality and an apparent 100 per cent morbidity in a captive colony of squirrel monkeys (Saimiri sciureus). The source of the infection could not be elucidated. Although most deaths were due to pulmonary oedema, one monkey probably died of heart and liver failure. These findings support the view that New World monkeys are unusually sensitive to Toxoplasma gondii infection. The similarity of the disease in these monkeys with that in immunocompromised human beings is an observation worthy of further investigation. PMID- 1452815 TI - Immunopathology in Aujeszky's disease virus-infected pigs exposed to fluctuating temperatures. AB - Pigs exposed to fluctuating temperatures (high, 30 +/- 2 degrees C; low, 4 +/- 1 degrees C) were intranasally inoculated with Aujeszky's disease virus (ADV). ADV infected pigs, exposed to the fluctuating temperatures, showed severe clinical signs and ADV in the nasal secretions persisted longer than in the ADV-infected control pigs kept at the normal temperature (20 +/- 2 degrees C). High concentrations of ADV were isolated from nasal secretions on the 1st day after inoculation of the virus. Pathologically, all ADV-infected pigs had non suppurative encephalitis and trigeminal ganglionitis. The lesions were more widely distributed in pigs exposed to fluctuating temperatures than in infected control pigs. Two infected pigs given the stress had severe malacic foci in the frontal lobe and four of them had prominent interstitial pneumonia. In the pigs exposed to fluctuating temperatures, a significant number of immunoglobulin containing cells, especially IgM-containing cells, did not respond to ADV infection. A significant (P < 0.01) difference in the number of IgG- and IgM containing cells was observed between the ADV-infected pigs exposed to the fluctuating temperature and ADV-infected control pigs, respectively. These results demonstrated that the stress of fluctuating temperatures enhanced the susceptibility to ADV infection. PMID- 1452816 TI - Neosporosis in the aborted fetus and newborn calf. AB - Protozoal encephalitic lesions were found in four aborted fetuses and one dead newborn calf. The organism was identified as Neospora caninum by immunoperoxidase. The brain lesions were of two forms. One was observed in three fetuses of 5 months gestation and was characterized by multifocal necrosis. The other was found in a 7-month fetus and in a newborn calf, and showed severe infiltration with macrophages and plasma cells containing IgG. This association, between the age of fetus and inflammation, may reflect development of the immune system in bovine fetuses. PMID- 1452817 TI - Isolation of Brucella melitensis from aborting ruminants in Jordan. AB - Thirty-four isolates (16.5 per cent) of Brucella melitensis were cultured from 206 samples from aborted, still-born or weak full-term animals and vaginal swabs from aborted animals. Twenty-six of 31 isolates from sheep were B. melitensis biovar 3. Two isolates were biovar 1 and one of these was the vaccine strain Rev 1. The three remaining isolates were from vaginal swabs and were not biotyped since B. melitensis biovar 3 had been isolated from the aborted fetuses. One of two isolates from cattle and one isolate from a goat were biovar 1. The remaining cattle isolate was biovar 3. PMID- 1452818 TI - From generation to generation. PMID- 1452819 TI - Managing change: strategies for continuing education. AB - Nurses who provide continuing education have a role, primarily through staff education, in helping to bring about change within their institutions. To fulfill this role requires that nurse educators understand the change process and anticipate the range of human responses to it. This article presents an overview of two change theories that incorporate strategies for CE offerings that facilitate the implementation of change. PMID- 1452820 TI - Nursing internships: taking a second look. AB - Nursing internships are associated with recruitment and retention efforts of hospitals to gain new nursing employees. They are recognized as a benefit to new nursing staff and the hospital as well. Reported to bridge the gap and ease the transition to registered nurse, internships have been reported in the literature for over 30 years. But how effective are they? This article reviews the recent literature for evidence that internship programs improve recruitment and retention, have a positive cost benefit ratio, and ease the role transition of newly employed nurses. PMID- 1452821 TI - Enjoyable learning experiences--an aid to retention? AB - Stress is related to job dissatisfaction and is a significant factor in high turnover rates for nursing staff. In the current labor market, all possible aids to retention need to be considered and innovative approaches need to be tried. Perhaps one of the most powerful retention tools, laughter, is being overlooked. Research indicates that laughter and humor have positive effects by reducing stress and enhancing the immune system. Stress within the hospital environment contributes to burnout. Burnout results in absenteeism, decreased productivity, and turnover. Incorporating laughter and humor into educational programs is one strategy to reduce stress and may be an antidote for burnout. A game called "Not So Trivial ... Protective Pursuit" was used with 150 staff on the evening and night shift. The observed effects were very positive. The implications are that nurse educators can make a significant contribution to preventing hospital burnout by making learning experiences enjoyable. PMID- 1452822 TI - Using a game format to improve compliance with required review of hospital standards and policies. AB - Maintaining quality patient care requires frequent review of hospital standards and policies. This repetition, however, proves to be boring and not much fun, resulting in poor staff participation. The anticipation of a visit from the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) provided the impetus for individual nursing units to develop a means of addressing this problem. Utilizing shared governance concepts, staff developed a game format to stimulate interest. This not only made learning and reviewing fun, but also empowered the staff to become accountable for the quality of their work. This article describes the development of the game format, its implementation, and evaluation of its effectiveness. PMID- 1452823 TI - Preceptors: a comparison of their perceived needs before and after the preceptor experience. AB - This study supports the need to establish selection criteria that emphasize an individual's clinical experiences as part of the preceptor application process. This study further supports the need to provide a comprehensive workshop to prepare participants for the preceptor role. PMID- 1452824 TI - An orientation program for new graduate nurses: the basis of staff development and retention. AB - The nursing shortage and an increased demand for obstetric nurses led a Central Texas hospital to hire new graduates for the Level Three obstetric unit. This change in hiring policy necessitated a reevaluation of the orientation program resulting in a new approach in staff development. A three-phase program was developed beginning with orientation and socialization of the new staff member, continuing with the development of advanced skills, and leading to assignments of complex cases after completing appropriate educational programs. The program has fostered autonomy in the experienced staff nurse and increased job satisfaction as measured by advancement in the career ladder and retention rate. The program is regularly monitored by chart and peer review audits, as well as by the orientees' six-week and six-month evaluations. PMID- 1452825 TI - A 10-year follow-up study: nurse refresher program. AB - A university-based school of nursing has provided a refresher course for inactive nurses since 1980. In 1985, the nursing shortage and declining enrollments in generic nursing schools emphasized the need to return inactive nurses to work. This article describes the 10-year follow-up evaluation of the course with attention to the long-term effectiveness in returning inactive registered nurses to the work force. This study also describes the employment profile of course graduates and the continuing education acquired by respondents since completing the course. Of the 71 respondents, 91% successfully reentered the work force and remained employed in nursing. Nearly half of these individuals were employed in acute care settings. Further, the employment profile of the working graduates showed that 74% had obtained an initial nursing position and remained in it until the time of the follow-up evaluation. Implications of the study and changes planned for the course are also described. PMID- 1452826 TI - RN students' satisfaction with clinical teaching in a distance education program. AB - This study examined student satisfaction with clinical teaching and student perceived difficulties in three introductory nursing courses offered by distance education. The sample consisted of 41 registered nurse respondents enrolled in a baccalaureate nursing program. Quantitative and qualitative data were collected by mailed questionnaire. The results indicate that the degree of satisfaction with the clinical teacher role was high and that unfamiliarity with the clinical settings and roles were perceived as difficulties. As well, the qualitative data suggest that RN learners need gradual exposure to self-directed learning to acquire these skills. PMID- 1452827 TI - Efficacy of a substance abuse primary prevention skills conference for nurses. AB - A conference on substance abuse prevention skills was presented by the New York State Nurses Association (NYSNA) to provide nurses with skills to help patients in various practice settings. Information covered assessment, intervention, and tools for interviewing and identifying resources. A six-month follow-up evaluation showed that the majority of the participants incorporated the skills in their nursing practice primarily in interviewing and use of assessment questions. Directions for future conferences were identified. PMID- 1452828 TI - A practical approach to CPR recertification. PMID- 1452829 TI - Characterization and kinetics of gastric emptying of peptides derived from milk proteins in the preruminant calf. AB - The gastric emptying kinetics of peptides derived from milk protein were studied in vivo in preruminant calves by collecting and characterizing the whole effluent leaving the stomach for 12 h after ingestion of crude skim milk. Peptides were isolated by reversed-phase HPLC and identified. Particular attention was paid to biologically active peptides and to peptides that could be precursors of biologically active sequences. A gastrin inhibitor, the caseinomacropeptide, was emptied from the stomach only during the first 0.5 h of digestion and rapidly hydrolysed. Precursors of immunostimulatory peptides from alpha s1- and beta caseins were emptied throughout digestion in the gastric effluent. A precursor of beta-casomorphins (peptide 58-93 of beta-casein) was emptied from the stomach 3.5 h after the meal when it was taken on an empty stomach. From this precursor, peptides that may be resistant to hydrolysis by intestinal peptidase were obtained after in vitro hydrolysis by pancreatic enzymes. A phosphopeptide (fragment 110-142 of alpha s1-casein) was also found in digesta after a few hours of digestion. When the meal was not taken on an empty stomach, these peptides were emptied in the first digesta at a low concentration. The potential activity of these peptides is discussed. The results support the hypothesis that active sequences could still be present in the gut after the action of pancreatic enzymes. PMID- 1452830 TI - Cost benefit analysis of bovine mastitis in the UK. AB - Bovine mastitis reduces the yield and quality of milk and increases the rate of culling and veterinary costs. This reduces the profitability of farm milk production but the calculation of the extent of this economic loss is complex because of the many factors involved and deficiencies in the evidence on the relationship between the disease and various production factors. This paper examines the available evidence for the UK and provides a consistent analytical framework within which the benefits arising from reduced mastitis in dairy herds constrained by quota can be considered. It is estimated that since 1970 the farms that have followed the recommended control procedures have reduced the average annual number of cases of clinical mastitis from 135 to 40 cases/100 cows each year, while the quarters remaining uninfected for a whole year has increased from 65 to 80% of the total quarters. The costs of the main control procedures (e.g. 8.60 pounds/cow for dry-cow therapy and teat dipping or spraying) are broadly covered by the reduction in clinical mastitis, leaving the benefits of reduced subclinical infection (e.g. 3810 pounds for a 100 cow herd unconstrained by quota and achieving the average reduction in infection) as a substantial bonus. The imposition of quotas reduces the financial benefit of mastitis control but it still remains a worthwhile investment. The results of this analysis can be used to suggest maximum costs of additional new control measures produced by research. It also indicates that there is considerable value in production research which gives more precise knowledge of production systems, thus allowing producers to respond optimally to quota cuts. PMID- 1452831 TI - Effect of mastitis on plasminogen activator activity of milk somatic cells. AB - This study was conducted to examine the effects of mastitis and stage of lactation on plasminogen activator (PA) activity in milk somatic cells. An assay system, which measures the plasmin-mediated hydrolysis of the chromogenic substrate D-valyl-leucyl-lysine p-nitroanilide, was used to assess PA activity present within milk somatic cells. Milk cell associated PA activity was increased (P < 0.05) by 50% in the presence of fibrin fragments. This suggests that milk somatic cells contain tissue PA which, unlike urokinase PA, is preferentially activated in the presence of fibrin fragments. An increase of the milk somatic cell count from < 5 x 10(4) to > 10(6) cells/ml resulted in an 8-fold increase in PA activity per cell. Elevated levels of PA activity were associated with milk somatic cells isolated from mastitic quarters obtained from cows in early (< 4 months in lactation) or late lactation (> 8 months in lactation). We conclude that PA activity is increased during severe mastitic inflammation. Although the physiological function of this enzyme is as yet unclear, we propose that it may be involved in the conversion of plasminogen to plasmin, contributing to the higher levels of plasmin occurring in milk isolated from mastitic quarters. PMID- 1452832 TI - Transepithelial potential difference in the goat mammary gland and its change during hand milking, and administration of oxytocin and catecholamines. AB - The reaction of secretory epithelium and myoepithelial cells in the alveoli to hand milking and i.v. injection of oxytocin and catecholamines was studied in lactating goats. The reaction of secretory cells was assessed by changes in the transepithelial (blood-milk) potential difference (PD), and the contractile reaction of myoepithelial cells by the growth of intramammary pressure (IP). The initial value of PD was 24.6 +/- 0.6 mV, that of IP 3.32 +/- 0.08 kPa (24.9 +/- 0.6 mmHg). Milking and oxytocin administration caused a rise in PD and an increase in IP. After noradrenaline and adrenaline injections two-phase PD changes and a short-term rise in IP were recorded. Isoproterenol, a beta-agonist, caused a rise in PD but did not affect IP. Phenylephrine, an alpha-agonist, caused two-phase and one-phase changes in PD. Simultaneously, a rise in IP was recorded. The results show that the reaction of the mammary gland to the substances administered is complex. Myoepithelial and secretory cells respond differently to short-term rises in the level of mediators and hormones in the blood. PMID- 1452833 TI - Aetiology of disturbed milk ejection in parturient primiparous cows. AB - Milk flow in nine primiparous cows with disturbed milk ejection (D) and in six corresponding control animals (C) with normal milk removal was recorded during machine milking and blood samples were taken before and during milking to determine plasma oxytocin, vasopressin, prolactin, cortisol, oestradiol-17 beta, luteinizing hormone, progesterone and beta-endorphin concentrations. Manual teat stimulation before milking lasted for 1 min. After milk flow had stopped, air was blown into the vagina for 2 min. When milk flow had stopped again, 1 i.u. oxytocin and finally 10 i.u. oxytocin were injected to remove residual milk. During and after teat stimulation, oxytocin remained basal in D, but increased in C, whereas prolactin increased in both groups. While 94% of total milk was obtained in C during this period, only 9% could be removed from D, indicating lack of alveolar milk ejection. During vaginal stimulation, oxytocin increased transiently in D and more than by teat stimulation in C. This allowed the removal of 75% of milk in D, whereas almost no more milk was available in C. After oxytocin injections, 3 and 16% of residual milk were obtained in C and D respectively. Basal oestradiol-17 beta concentration was higher in D than in C (11.6 and 2.0 ng/l respectively), whereas beta-endorphin level was lower (24.1 and 86.6 micrograms/l respectively). Basal concentration of luteinizing hormone and progesterone, and concentration of cortisol and vasopressin before and during milking were comparable in C and D. We conclude that in cows with disturbed milk ejection afferent nervous pathways to the hypothalamus were intact, because prolactin was released by teat stimulation. However, oxytocin was only released by vaginal stimulation, i.e. milk ejection was centrally inhibited during teat stimulation. PMID- 1452834 TI - Effect of methionyl bovine somatotropin in a prolonged-release vehicle on milk production, hormone profiles and health in dairy cows. AB - Milk production of dairy cows in 14 herds was increased by 3.8-32.1% by the administration of recombinant methionyl bovine somatotropin (bST) in a sustained release vehicle at 14 d intervals at 40-94 d post partum. A greater response in multiparous than in primiparous cows was found in cows turned out to graze spring pasture. Administration of recombinant bST resulted in elevated plasma bST during the first 9 d after injection. Clinical characteristics such as respiration, heart rate and body temperature were unaffected by bST treatment, as were blood erythrocyte and leucocyte counts, haemoglobin concentrations and haematocrit values. Plasma levels of glucose, free fatty acids, urea and P, and serum alanine aminotransferase and aspartate aminotransferase were not affected by bST treatment, and acetone was not detected. No adverse effects of bST on general health, infection status of mammary glands, mastitis incidence and reproduction were found. PMID- 1452835 TI - Heat-related changes to the hydrophobicity of cheese whey correlate with levels of native beta-lactoglobulin and alpha-lactalbumin. AB - Correlations were identified between levels of the native whey proteins, beta lactoglobulin and alpha-lactalbumin and the surface and total hydrophobicities of cheese whey in response to different heat treatments. Heat-induced changes in the native beta-lactoglobulin content and surface hydrophobicity of whey exhibited the most significant linear relationship while correlations between total hydrophobicity and the native proteins were less significant because of an atypical rise in the n-heptane-binding capacity of whey after high-temperature treatment. The content of native beta-lactoglobulin in whey was more sensitive to heating than the content of native alpha-lactalbumin, while heat-related changes in the total hydrophobicity of whey were generally greater than similar changes in surface hydrophobicity. PMID- 1452837 TI - Purification of alpha s-, beta- and kappa-caseins by batchwise ion-exchange separation. PMID- 1452836 TI - Studies on antimutagenic effect of milk cultured with lactic acid bacteria on the Trp-P2-induced mutagenicity to TA98 strain of Salmonella typhimurium. AB - The inhibitory effects of cultured milk using 76 strains of lactic acid bacteria isolated from milk products were investigated on the mutagenicity of 3-amino-1 methyl-5H-pyrido[4,3-b]indole (Trp-P2), a tryptophan pyrolysate for Salmonella typhimurium TA98. Each cultured milk sample displayed its characteristic antimutagenic effect against the mutagenicity of Trp-P2. The milk cultured with Lactobacillus acidophilus LA106 (LA2) showed the highest inhibition of 82.1% among the strains used. Milk samples cultured with Lactococcus lactis subsp. lactis, Lll103 (10-3) and Lll102 (KM) also exhibited higher inhibition percentages. PMID- 1452838 TI - Preparative-scale purification of bovine caseins on a cation-exchange resin. PMID- 1452839 TI - Gredos goats' milk cheese: microbiological and chemical changes throughout ripening. PMID- 1452840 TI - Salmonellae, salmonellosis, and dairy foods: a review. AB - Salmonellae continue to be a major concern for the dairy industry because these bacteria have caused recent outbreaks of illness and have been isolated from various dairy products in the market place. Salmonellae are generally not heat resistant and normally grow at 35 to 37 degrees C, but they can grow at much lower temperatures, provided that the incubation time is suitably extended. To minimize problems, foods should be held at or below 2 to 5 degrees C at all times. Both conventional and rapid methods are available to isolate salmonellae from dairy foods and to identify the bacteria. Salmonellae behave differently in different kinds of cheese: they survived in ripening Cheddar cheese for up to 7 mo at 13 degrees C and for 10 mo at 7 degrees C; in coldpack cheese food for several weeks, depending on the pH and preservative used; and in Domiati cheese 13 to 36 d, depending on the manufacturing process used. When Mozzarella cheese was made, temperatures of stretching and molding (60 degrees C) killed all salmonellae present, but, in cottage cheese, survival of the pathogen depended on the cooking temperature of curd. Spray drying of skim milk killed substantial numbers of salmonellae, but some survivors remained. Butter readily supported growth of salmonellae at room temperature, and neither freezing nor refrigeration for brief periods eliminated salmonellae from butter. Use of appropriate hygienic procedures, e.g., Hazard Analysis Critical Control Point system, during processing should reduce the likelihood of salmonellosis outbreaks associated with dairy foods. PMID- 1452841 TI - Growth and activities of Lactococcus lactis in milk enriched with low mineral retentate powders. AB - The growth and activities of three strains of Lactococcus lactis ssp. cremoris (Wg2, E8, and HP) and their proteinase-negative variants were studied in skim milk enriched with three types of retentate powder. The performance of these strains in enriched milks was compared with that determined in reconstituted skim milk. Proteinase-positive strains of L. lactis ssp. cremoris exhibited higher maximum specific growth rates than protease-negative variants. Moreover, maximum specific growth rates of lactococci were lower in skim milk than in enriched milk with a high buffering capacity. The performance of proteinase-positive strains was better than that of proteinase-negative variants. Growth of proteinase positive lactococci in milk media increased alpha-amino groups as determined by the increase of equivalent glutamic acid concentration. Available alpha-amino groups decreased with proteinase-negative variants. Proteinase-positive strain Wg2 exhibited the most proteolytic activity but showed the least specific overall productivity of lactic acid despite high biomass concentration in milk. Among proteinase-positive lactococci, strain E8 produced more lactic acid than other strains, and, among proteinase-negative variants, strain HP had the best specific overall productivity of lactic acid. PMID- 1452842 TI - Production of an electrolyte beverage from milk permeate. AB - The objective of this study was to prepare shelf-stable electrolyte beverages from milk permeate. The average composition of permeate was 4.59% total solids and .40% ash. Lactose was hydrolyzed (approximately 80%) with a commercial fungal lactase enzyme. Additional sweetness was provided by sucrose. The pH was reduced to 3.5 to 3.8 by the addition of citric acid. Shelf-stable products were made using four processes: 1) UHT followed by aseptic filling, 2) heating of filled bottles to 85 degrees C for 30 min, 3) addition of .05% benzoate, and 4) nanopore filtration. The mineral composition of the finished product, expressed in parts per million, was calcium, 150; phosphorus, 157; magnesium, 43; potassium, 1166; sodium, 286; iron, 17; copper, 8; and zinc, 3.4. Listeria monocytogenes, Salmonella dublin, Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae grew well when they were inoculated into unacidified, hydrolyzed permeate. None of these organisms were isolated from properly processed products. A shelf-stable electrolyte beverage high in minerals was made from whole milk permeate. This beverage could be used to replace electrolytes lost from the human body. The production of a permeate beverage would help alleviate disposal problems of permeate. PMID- 1452843 TI - Vitamin A supplementation of Holsteins at high concentrations: progesterone and reproductive responses. AB - Five trials involving 168 Holstein cows and 20 heifers were conducted to determine the effect of vitamin A supplementation at high concentrations, 1 or 2 million IU, compared with 100,000 IU/d, on peripheral concentrations of progesterone and on several measures of reproductive performance. Supplemental vitamin A at high concentrations had no effect on circulating concentrations of progesterone in either cyclic or pregnant cows or on most measures of reproductive performance examined in trials. Thus, it was concluded that providing vitamin A at these high concentrations is not warranted. PMID- 1452844 TI - Evaluation of a system for rating edema in dairy cattle. AB - Our objective was to evaluate a subjective edema rating system to quantitate edema severity. Edema was evaluated with 20 nulliparous Holstein heifers from 3 wk before their expected calving date until 3 wk postpartum. Severity of udder edema was evaluated independently daily by five people throughout the 68-d experiment; a 10-point rating system (0 = no edema, 10 = severe edema) was used. One of the people developing the scoring system served as the official scorer. The accuracy of the rating system, defined as the closeness of test evaluator scores to official scores, was highest for scores 2 to 8. The precision of the system, identified by the standard error of the mean, was similar for each score in the rating system. The largest disagreement between official and test evaluator scores was evident postpartum. The large number of defined points in this rating system and the similarity between official and test scores in this study indicate the usefulness of this tool to evaluate precisely the severity of edema in dairy cattle. PMID- 1452845 TI - Influence of calcium chloride fed prepartum on severity of edema and lactational performance of dairy heifers. AB - Twenty Holstein heifers in a completely randomized design were used to evaluate the effects of prepartum dietary CaCl2 on the development and regression of edema and on subsequent lactational performance. Heifers were assigned to diets containing either 2.17% limestone or 1.5% CaCl2 (DM basis) at 3 wk before expected calving date. Except for the Ca sources, diets were identical. Test diets were only fed prepartum; at calving, all heifers were offered a lactation diet for 3 wk. Severity of edema was evaluated independently by five people daily throughout the experiment; a 10-point rating system was utilized to quantify the severity of edema. Calcium chloride reduced the severity of edema, although this response was most evident during the 1st wk that this salt was fed. The beneficial effects of CaCl2 on edema prepartum disappeared postpartum, when CaCl2 was removed from the diet. Indeed, edema was higher for heifers fed CaCl2 than for those fed limestone at 2 wk postpartum. Calcium chloride reduced DMI prepartum, but, following parturition, a compensatory increase in feed intake occurred. Postpartum daily DMI averaged 1.3 kg higher for heifers fed CaCl2 than for those fed the limestone diet prepartum. Milk yield and composition were somewhat lower for heifers fed CaCl2, although this response was most evident at 1 wk postpartum. Feeding CaCl2 prepartum to prevent milk fever also may reduce the severity of udder edema prepartum and increase feed intake during early lactation. PMID- 1452846 TI - Etiology of acetonemia in Norwegian cattle. 1. Effect of ketogenic silage, season, energy level, and genetic factors. AB - Plasma acetoacetate concentration in the 1st mo of lactation and its relation to BW change, milk yield, DMI, and BW postpartum were studied in 361 first lactation cows during 6 yr. The cows were fed concentrate at 6 and 3 kg/d. Calvings took place from August to December. Single observations for all cows were fitted by a multitrait animal model that accounted for all genetic relationships. Heritability for acetoacetate was .11 with a genetic correlation of .87 for milk yield, -.65 for weight change, and -.13 for BW postpartum. Acetoacetate was higher at 3 kg/d of concentrate than at 6 kg/d, and calving after 3 to 4 mo of indoor feeding was related to higher acetoacetate than was calving shortly after the pasture season. Acetoacetate was related to weight loss postpartum, but at a different degree in different years. In some years, compounds of the silage caused strongly elevated plasma concentrations of acetoacetate after feeding. Experiments were performed to compare hay with silages of different qualities. Rumen concentration of different amines 3 h postfeeding was taken as an index of the amine load of the cow. The concentration of several amines in rumen fluid were high after feeding ketogenic silage. PMID- 1452847 TI - Etiology of acetonemia in Norwegian cattle. 2. Effect of butyric acid, valeric acid, and putrescine. AB - A feeding experiment was performed on 16 cows in order to test the effect of naturally occurring substances in silage on forage intake, ketonemia, and milk yield. The cows were divided into a control group and three experimental groups. The cows in the three experimental groups were fed 100 g/d of putrescine, 200 g/d of valeric acid, or 200 g/d of butyric acid through a ruminal tube for 3 d. Butyric acid increased plasma acetoacetate; the effect was largest in high yielding cows. Putrescine influenced both milk yield and forage intake and may possibly be a contributory factor, alone or combined with other amines, for the development of ketonemia. Valeric acid did not influence feed intake or plasma acetoacetate concentration. A rapid method for acetoacetate analysis also is described. PMID- 1452848 TI - Ruminal in vitro degradability of protein in alfalfa harvested as standing forage or baled hay. AB - Eighty-nine samples, 45 of standing forage and 44 of baled hay, were collected from alfalfa harvested at various maturities over three cuttings each during 2 yr. Alfalfa was cut and conditioned mechanically; samples of standing forage were collected by removing bunches of forage from windrows and freeze-drying them. Forage was allowed to field cure and was harvested at an average 80% DM as small rectangular bales; samples of baled hay were collected by coring bales after storing for 3 to 6 mo. Samples were analyzed for DM, ADF, total N, fractions of total N present as ADIN, N degraded at 0 h, and potentially degradable protein N. Ruminal protein degradation rates and escapes were estimated using an inhibitor in vitro system, assuming that ADIN was unavailable and that ruminal passage rate was .06/h. Standing forage contained smaller fractions of ADIN and N degraded at 0 h, contained a larger fraction of potentially degradable N, and had more rapid degradation rates and lower estimated protein escapes than baled hay. Mean degradation rates and estimated escapes were .171/h and 24% for standing forage and .075/h and 40% for baled hay. There were no differences in degradation rate or estimated escape because of harvest year, and neither was significantly related to maturity or to ADF concentration. Results indicate a significant advantage in ruminal protein escape, compared with grazed alfalfa, for alfalfa harvested and stored as hay. PMID- 1452849 TI - In vivo degradation of protein in diets formulated for two degradabilities. AB - In vivo protein degradability of two basal diets and bacterial protein synthesis were determined in four lactating dairy cows equipped with ruminal and duodenal cannulas. The diets contained corn silage, high moisture corn, and either soybean meal or a 60:40 mixture of soybean meal and corn gluten meal. Diets had calculated ruminal protein degradabilities of 69.3 and 62.3%, respectively. Both diets contained approximately 14% CP and 21% ADF. Duodenal flows of total N, total protein N, microbial N, and duodenal recovery of ingested N tended to be higher for the soybean meal and corn gluten meal diet; ruminally degraded CP was significantly lower than for the soybean meal diet. Ruminal ammonia and plasma urea concentrations tended to be higher for the soybean meal diet, as were molar percentages of butyrate and valerate. Ruminal and total tract apparent digestibilities of CP and OM were not significantly different between diets. Ruminal degradation of protein in the two diets differed by the amount predicted by the NRC system for lactating cows, although absolute values were lower than most previous estimates for similar diets. PMID- 1452850 TI - Effect of fish meal and expeller-processed soybean meal fed to dairy cows receiving bovine somatotropin (sometribove). AB - Forty-eight multiparous cows were blocked by calving date and milk production and assigned randomly to a TMR formulated to contain 68 or 55% of dietary CP as ruminally degradable CP. Diets contained corn silage, alfalfa haylage, and ground corn. Supplemental CP was soybean meal for the control diet or a combination of soybean meal, expeller-processed soybean meal, and fish meal for the low degradable protein diet. Two 10-wk phases began on d 31 +/- 3 (phase 1) and 110 +/- 7 postpartum [phase 2, all cows received subcutaneous implantations of pelleted (400 mg) bST (sometribove) every 14 d]. Dietary energy, CP, ruminally degradable CP, NDF, and ADF were similar between dietary treatments. Production of FCM increased in response to bST but was not affected by dietary treatment. Cows fed the expeller-processed soybean meal and fish meal TMR produced milk that contained less milk fat in phase 1 and less milk protein content in both phases. The DMI, BW, and body condition scores were not affected by diet. Hematocrit, plasma urea N, albumin, total protein, creatinine, glucose, and serum insulin were similar between dietary treatments. Replacing soybean meal with expeller processed soybean meal and fish meal did not affect ruminal degradation of protein or milk production but decreased milk fat and protein contents. PMID- 1452851 TI - Fatty acids, calcium soaps of fatty acids, and cottonseeds fed to high yielding cows. AB - We examined the effects of dietary fat as cottonseed, fatty acids, or calcium soaps of fatty acids in the rations of high yielding lactating cows receiving low forage. Experiments were with isoenergetic, isonitrogenous diets containing equal amounts of forage. Inclusion of up to 510 g/d of fatty acids in the ration enhanced FCM yield. With cottonseed, increased FCM was mainly due to increased fat yield. Dietary fatty acids tended to increase milk in mid and late lactation and to decrease fat percentage. Calcium soaps of fatty acids enhanced FCM, particularly in early lactation. Feeding cottonseed and fatty acids together did not enhance yield. Effects described may be attributed in part to changes in ruminal fermentation in which cottonseed increased acetate concentrations and fatty acids decreased the ratio of acetate and butyrate to propionate and in part to enhanced efficiency of milk yield when fat was included in the ration. PMID- 1452852 TI - Weekly balancing crude protein in diets for Holstein cows throughout lactation using one versus two grains. AB - Holstein cows (n = 72, 28 primiparous) were fed for ad libitum intake a forage mixture (corn and haycrop silages, 63:37 DM) and a 71:29 ratio of two grain mixtures (13.8 and 36.2% CP, DM basis) at 1 kg/2.5 kg of the previous day's milk during 1 to 28 DIM (covariate period). Thereafter, rations were balanced and adjusted for energy and CP weekly based on monthly DHI data, forage analyses, and NRC requirements. Cows were blocked by parity (1 vs. greater than 1) and assigned randomly to receive one grain (blend of 13.8 and 36.2% CP grains, herd mean) or two grains according to individual needs. Daily yields of milk, 4% FCM, SCM, and resulting intakes of grain were higher for cows fed two grains, but the increase in daily DMI and the decreases in daily forage intake and SCM:grain ratio were not significant. Fewer pluriparous cows (3 vs. 8 out of 19) on the two-grain treatment conceived after first service, but overall services per conception (1.97) were equal. Percentage of cows with SCC below linear score 4 (91%) was equal between treatments. Means adjusted by covariate 4% FCM resulted in more modest treatment effects. Advantage of two-grain versus one-grain treatment for milk per day was 7.7% for parity 1 and only 1.6% for parities greater than 1; corresponding responses (nonsignificant) for 4% FCM were 2.8 and 4.3, respectively. Forage DMI depressions on two-grain treatment were not significant. When covariate-adjusted means were used, the advantage in income over feed cost for individualized feeding of CP was $106 and $36/yr per cow in parities 1 and greater than 1 when cows produced 8209 kg (313 DIM) and 8527 kg (320 DIM) of milk, respectively. PMID- 1452853 TI - Epiphytic microflora on alfalfa and whole-plant corn. AB - Epiphytic microflora were identified and counted on four cuttings of alfalfa, each harvested at three stages of maturity, and on three whole-plant corn hybrids. Enterobacteriaceae were predominant on both crops. Yeasts and molds also were major epiphytic microorganisms on whole-plant corn. The group--including lactobacilli, pediococci, and leuconostocs, which are genera that produce lactic acid and thus are instrumental in silage preservation--constituted only a small proportion of the total population (less than .5%) on both crops. Lactate fermenting clostridial spores were not detected on standing alfalfa, and occurrences of these spores on standing corn plants were due to soil contamination from rainfall prior to harvest. The numbers of epiphytic microorganisms, except for the lactobacilli, pediococci, and leuconostocs group, were higher on standing corn than on alfalfa. The epiphytic microflora on alfalfa increased with increasing temperature during the growing season. However, neither cutting number nor maturity affected the epiphytic microflora on standing alfalfa, and wilting following mowing had little effect on most populations. Higher temperatures during wilting increased yeast and mold counts but had no effect on other microbial counts. The chopping process tended to increase the epiphytic microflora populations compared with those on the standing crops, and the group containing lactobacilli, pediococci, and leuconostocs was most enhanced. Only yeast and mold counts on the chopped alfalfa increased with greater DM content and buffering capacity. PMID- 1452854 TI - In vitro effects of the thiopeptide A10255 on ruminal fermentation and microbial populations. AB - Experiments used unadapted mixed cultures of ruminal microorganisms in batch or continuous culture fermentation to investigate the effect of a thiopeptide, A10255, on ruminal fermentation and microbial populations. After 24 h of fermentation in batch culture, addition of A10255 (.5 to 20 ppm of the culture fluid) to 0, 45, 60, and 75% concentrate diets had no effect on total VFA but increased molar proportion of propionate and decreased butyrate. The molar proportion of acetate was decreased by treatment only in the 0 and 75% concentrate diets. The increase in molar proportion of propionate by 20 ppm of A10255 was less than the increase caused by a similar concentration of monensin. The same concentration of A10255 (20 ppm) decreased ADF digestion less than 20 ppm of monensin. In continuous culture, A10255 (33 mg/kg of dietary DM) did not affect total VFA concentration, culture pH, OM digestion, or ADF digestion. Ruminal bacterial populations of total anaerobes and lactate-producing, lactate utilizing, cellulolytic and amylolytic bacteria were unaffected by treatment. However, molar proportions of acetate, butyrate, and isovalerate were decreased, and propionate was increased, by addition of A10255. PMID- 1452855 TI - Effects of lasalocid and undegradable protein on growth and body composition of Holstein heifers. AB - Effects of lasalocid (0 or 200 mg/d per head) and undegradable intake protein (32 vs. 42% of CP in concentrate) on growth and body composition were evaluated using 32 Holstein heifers (253 kg initial BW, SE = 4). Heifers were housed in an open barn in eight pens of 4 heifers and fed 12.7 kg per pen daily of experimental concentrate with medium quality fescue hay for ad libitum consumption for 12 28-d periods. Body measurements were taken every 28 d; ultrasonic fat and muscle depths at the 13th rib, empty body fat, and protein were measured every 84 d. Heart girth and fat and muscle depth at the 13th rib increased when lasalocid and undegradable protein were fed individually, but not in combination. Rates of average daily gain and feed efficiency were not increased significantly when lasalocid and undegradable protein were fed. Data suggest that the combination of lasalocid and undegradable protein may have impaired microbial protein synthesis in the rumen, thereby influencing changes in body composition. PMID- 1452856 TI - Effect of extra energy as fat or milk replacer solids in diets of young dairy calves on growth during cold weather. AB - The effects of feeding two levels of supplemental fat and extra milk replacer solids on Holstein calves housed in hutches during the winter were investigated. Fifty calves (10 per treatment) were assigned to the following dietary treatments: 1) milk replacer (control) reconstituted to 12.5% DM fed at 10% of BW (adjusted weekly), 2) same as treatment 1 plus 113 g/d of supplemental fat, 3) milk replacer reconstituted to 15% DM and fed at 10% of BW (adjusted weekly), 4) same as treatment 1 plus 226 g/d of supplemental fat, and 5) milk replacer reconstituted to 15% DM fed at 14% of BW (adjusted weekly). Half the amount of milk replacer consumed during wk 4 was fed during wk 5, and calves were weaned to dry feed at 35 d of age. A pelleted starter was offered for ad libitum intake throughout the 42-d trial. Gains in BW were greater for calves fed 226 than 113 or 0 g/d of supplemental fat (d 3 to 28). Calves fed milk replacer reconstituted to 15% DM at 14% of BW had greater BW gains during d 3 to 28 than control. Starter consumption was similar between groups receiving 113 and 0 g/d of fat supplement but lower in the group fed 226 g/d. Extra milk replacer solids in diets increased fecal scores to levels greater than those of calves in other groups. The benefit of fat supplementation of milk replacers was manifested as increased BW gain during the 1st mo of life. PMID- 1452857 TI - Genetic and environmental relationships among somatic cell count, bacterial infection, and clinical mastitis. AB - Incidence of bacterial infection in 9784 lactations of 7763 cows in 31 herds, SCC in 32,448 lactations of 19,764 cows from 54 herds, and incidence of first parity mastitis recorded in the first lactations of 148,143 cows in 828 herds were analyzed. Bacterial infection was analyzed dichotomously by both threshold and linear models. The effects of parity, season, stage of lactation, and parity by stage of lactation interaction on SCC were estimated. Heritability of mean lactation log SCC--corrected for the effects of parity, season, and stage of lactation--varied from .13 to .27 for all parities in different data sets. Heritability of bacterial infection was .04 for the threshold model and .02 for the linear models. Heritability of field-recorded mastitis was .01. The genetic correlation between bacterial infection and SCC was near unity, but the genetic correlation between SCC and mastitis was .3. Selection for lowered SCC should reduce incidence of bacterial infection by 2% per unit of selection intensity. PMID- 1452858 TI - Genetic analysis of fertility traits in Israeli Holsteins by linear and threshold models. AB - Conception rates of Israeli Holstein cows and heifers were analyzed separately by linear and threshold models. Fixed effects for both data files were insemination number, AI institute, geographical region, and calendar month. Analysis of cows also included the fixed effects of parity, calving status, and DIM at insemination. Random effects included in the models were herd-year-season, insemination technician, sire of cow, and service sire. Fixed effect solutions for heifers and cows were not similar. For cows, insemination month had the greatest effect on conception rate. Heritability of conception rate ranged from 2 to 3.5% for heifers and from 1 to 2% for cows. Correlations between corresponding threshold and linear model random effect solutions were all greater than or equal to .99. Correlations between heifer and cow analyses for sire and service sire solutions were less than .4. Analysis with an incorrect herd-year-season variance component affected only the technician solutions. PMID- 1452859 TI - Associations between milk protein polymorphisms and milk production traits. AB - Associations between milk protein genotypes and milk production traits were estimated from 6803 first lactation records. Exact tests of associated hypotheses and unbiased estimates of genotype effects were from an animal model. Milk protein genotype effects were estimated using a model in which each milk protein gene was analyzed separately (single-gene analysis) and a model in which all milk protein genes were analyzed simultaneously (multigene analysis). The results of the two models indicate that some effects ascribed to certain milk protein genes in the single-gene analysis are not effects of the milk protein gene itself but of linked genes. Results from this study and from literature indicate that the kappa-casein gene or a very closely linked gene affects protein percentage, and the beta-lactoglobulin gene or a very closely linked gene affects fat percentage. Furthermore, effects of beta-casein genotypes on milk production, fat percentage, and protein yield were significant, and beta-lactoglobulin genotypes had significant effects on milk production and protein yield. It is less clear whether those effects are due to effects of milk protein genes themselves or to effects of linked genes. PMID- 1452860 TI - Heat stress and milk production in the South Carolina coastal plains. AB - A model developed for the South Carolina coastal plains relates hours with temperature-humidity index values above 74 and 80 to summer season daily milk production. When tested on an independent production data set for 1985, the root mean square model error was less than 1.3 kg/d per cow. The model can be used to develop expected summer season dairy production climatologies. Real-time milk production forecasts obtained using daily predicted maximum and minimum temperatures can be used in herd management to reduce effects of heat stress on productivity. PMID- 1452861 TI - External and internal markers for appraising site and extent of digestion in ruminants. AB - Digesta markers are used routinely to calculate fecal output and to estimate kinetics within the digestive tract. A marker suitable for estimating fecal output may not be a suitable kinetic marker because of problems with marker migration, phase separation, inhibition of digestion, osmotic effects within the gut, and quantitation. Marker validity should be checked when possible based on alternative methods (e.g., fecal output and ruminal evacuation). Certain parameters, such as pool size and passage rate, that can be estimated with markers cannot be measured by other noninvasive procedures. Nevertheless, only when marker results are verified by other methods can one evaluate the magnitude of error associated with assumptions inherent in marker mathematics (steady state, instantaneous mixing, and first-order kinetics). When marker results do not meet expectations, marker failure, rather than inadequate knowledge of gastrointestinal function or analytical difficulties, is blamed. No marker is ideal, but research to compare markers is useless if results are not related to direct flow or output measurements. Marker results often are adjusted for marker recovery based on the premise that analysis is precise and that losses are constant. Such adjustment is appropriate only if the error is analytical and proportional. Despite imprecision in marker procedures, inherent variation may be small relative to other sources of variation (e.g., gut physiology, diet, environment, and feed intake). Even though absolute values may be imprecise and inaccurate, marker-based estimates usually provide reliable information about the direction and extent of kinetic changes induced by treatments. PMID- 1452862 TI - Markers for quantifying microbial protein synthesis in the rumen. AB - Measurement of ruminal microbial protein is necessary to quantify ruminal escape of dietary protein and microbial yields. Microbial markers used most widely have been the internal markers, diaminopimelic acid and nucleic acids (RNA, DNA, individual purines and pyrimidines, or total purines), and the external isotopic markers (e.g., 15N and 35S). Combined with digesta flow markers in ruminally and abomasally or intestinally cannulated ruminants, microbial yields can be estimated. An ideal marker system must account for both the bacterial and protozoal pools associated with both the fluid and particulate phases of digesta. No marker has proven completely satisfactory; hence, yield estimates are relative rather than absolute. Total purines represent robust microbial markers that should be adaptable by most investigators. Principal concerns about total purines relate to unequal purine: N ratios in protozoal and bacterial pools and to the need to assume that dietary purines are completely degraded in the rumen. A theoretically sounder, but more costly, method is continuous intraruminal infusion of 15N ammonium salts. However, 15N enrichments of bacterial and protozoal pools are not equal, so the basis for calculating microbial yield in faunated ruminants is uncertain. Urinary purine excretion may prove to be a noninvasive method for estimating microbial protein yields in intact dairy cows. PMID- 1452863 TI - Initial biological testing of root canal sealing materials--a critical review. AB - A number of systems for the biological testing of dental materials have been suggested. This paper presents a critical review of the protocols suggested in the ISO standards for the initial and secondary biological testing of root canal sealing materials. PMID- 1452864 TI - Prevalence and distribution of cervical dentine hypersensitivity in a population in Rio de Janeiro, Brazil. AB - The prevalence, distribution and possible causal factors of cervical dentine hypersensitivity were studied in a population from a Marine Dental Clinic in the city of Rio de Janeiro, Brazil. A total of 635 patients were examined for the presence of cervical dentine hypersensitivity by means of a questionnaire and intraoral tests (air and probe stimuli). There were 157 patients (25%) reporting to have hypersensitive teeth, but only 108 patients (17%) were diagnosed as having cervical dentine hypersensitivity. The prevalence of hypersensitivity was higher among females than males, but this difference was not statistically significant. Most females with hypersensitivity were aged 20-49 and most males were aged 40-59. Incisors and premolars had the highest prevalence of dentine hypersensitivity to air and probe stimuli, while molars had the lowest. The presence and history of dentine hypersensitivity were positively correlated with previous exposure to periodontal treatment. Only a few of the patients who claimed to have dentine hypersensitivity had tried treatment with desensitizing toothpastes or sought professional help. PMID- 1452865 TI - Secondary retention of permanent molars: a report of five families. AB - The aetiopathogenesis of secondary retention is not fully understood, but heredity is involved in at least some cases. In this study first-degree relatives of 52 patients with secondary retention of permanent molars were screened for the presence of the same phenomenon in their dentition. Familial occurrence could be shown in five families. The pedigrees are compatible with autosomal dominant inheritance. HLA phenotypes and blood groups ABO, rhesus and P1 were studied in two families. The lod scores for linkage with secondary retention were added to previously reported information. The lod score for linkage for blood group system P increased from +0.940 to +1.475 at a recombination fraction of 5 per cent. It is concluded that secondary retention of permanent molars is an aetiologically heterogeneous condition in which some cases are caused by the presence of an abnormal autosomal dominant gene. PMID- 1452866 TI - A critical comparison of dentifrice abrasion scores on dentine recorded by gravimetric and radiotracer methods. AB - Dentifrice abrasivity on dentine is conventionally ranked by various in vitro methods. The abrasivity of selected dentifrices in Switzerland was ranked in 1985 by the gravimetric and in 1989 by the radiotracer method. Because same-named brands of dentifrices were differently ranked by these methods, Swiss clinicians were unsure which ranking to follow. This paper lists the errors known to occur in both techniques, but unfortunately it is difficult to quantitate the magnitudes of these errors. Consequently, it is impossible to determine which method yields the more reliable results. Thus, researchers should look into the problem of dentifrice abrasion scores and try to formulate tests which could simplify the selection of brand-named dentifrices by clinicians and the consumers. PMID- 1452867 TI - Cavity convergence angles for direct composite inlays. AB - Direct composite inlays may sometimes be difficult to remove from the cavity following primary polymerization. The aim of this work was to find the lowest cavity convergence angle (taper) which would allow reliable inlay removal. Cavity finish and cavity size were also taken into account. Standardized mesio-occlusal distal cavities of 6 degrees taper were cut into 10 teeth of varying mesiodistal width and finished with either 12-bladed tungsten carbide or 25 microns diamond burs. After separating medium had been applied. Coltene Brilliant Dentin composite resin was packed into the cavity and light cured. The force required to remove the inlay was measured with an Instron Universal Testing Machine. The cavities were then refinished with the alternative finish and the experiment repeated. The same sequence was used for cavities of 12 degrees and finally 18 degrees convergence angle which were cut consecutively in the same 10 teeth. Force levels related to cavity convergence angle, cavity finish and tooth size were tested by ANOVA and regression analysis. The forces required to remove some of the inlays from the 6 degrees, and to a lesser extent 12 degrees angled cavities, proved unacceptably high, while an 18 degrees convergence angle resulted in statistically significant lower forces which were unlikely to damage tooth or inlay. Cavity finish and tooth size did not influence inlay withdrawal force. PMID- 1452868 TI - Trigeminal somatosensory evoked potentials: a normal value study. AB - Normal somatosensory evoked potentials were obtained from the lower lip of 40 volunteers. Efforts were made to exclude artefact. A consistent triphasic wave form of three peaks and troughs was defined. There were greater variations in amplitude than latency between subjects. Statistically, one side of the lower lip can be used as a control for the contralateral side, but it may not be possible to have reliable normal values between subjects. Somatosensory evoked potentials may however represent an objective method of evaluating trigeminal sensory nerve function. PMID- 1452869 TI - A confocal microscopic evaluation of the interface between Syntac adhesive and tooth tissue. AB - The aim of this study was to microscopically evaluate the effect of dentine smear layer thickness, tubular orientation and immediate stress application on a modern dentine bonding agent. Eighty mesial and distal wedge-shaped cavities were cut into dentine/cementum cervically in 40 extracted human lower third molars. The thickness of the dentine smear layer was reduced by polishing the cavity surface in half the samples. Each component of the bonding agent (Syntac: Ivoclar Vivadent) was labelled with a fluorescent dye, the unfilled resin being light cured for 30 s with the composite restoration placed in one increment and light cured for 40 s. The samples were longitudinally sectioned using a slow speed diamond saw underwater, either immediately or 24 h post placement. The sectioned surfaces were then viewed using a confocal optical microscope. The thickness of the smeared layer only effected the penetration of adhesive in dentine tubules which were separated from the pulp chamber by the cavity design. These areas were well filled with adhesive; however, areas communicating with the pulp chamber showed no penetration differences due to smear layer reduction by polishing. The interdependence of the adhesive components was illustrated by failure to achieve a well-impregnated tooth/adhesive hybrid layer when the materials were incorrectly handled. The Syntac/dentine interface was generally able to withstand the stress of sectioning immediately post placement, but showed signs of failure in the cavity line angle when the applied stresses were greatly increased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452870 TI - Determination of doughing and manipulation times of acrylic resin denture base material and a proposal for a specification for a packing plasticity test. AB - The doughing and manipulation times of a range of acrylic resin denture base polymers are presented in this study. The methods evaluated were: (i) probing following American Society for testing materials specification, F451-76; (ii) hole penetration following British Standard, 2487: 1989 and International Standard Organisation, 1567: 1988; (iii) probing using a penetrometer employing a 20 g load and 1 mm diameter needle; (iv) oscillating rheometer apparatus used at a fixed frequency of 1 Hz by sweeping through a programmed linear increase in strain. The results indicate that each of the methods is capable of evaluating the doughing and manipulation times of the unprocessed polymers. It is concluded that the Bohlin VOR Oscillating Rheometer is excellent for investigating the flow properties of denture base polymers but it cannot be recommended for a standards specification test because of the high cost. The penetrometer method has been shown to be superior to the current standards specification test and would be ideal for a packing plasticity standards test. PMID- 1452871 TI - Intraligamentary anaesthesia. AB - The introduction of specialized syringes in the late 1970s and early 1980s has led to an increase in the use of intraligamentary anaesthesia as a means of pain control in dentistry. This paper reviews the technique and its efficacy and considers the advocated advantages and disadvantages of the method in the light of the published scientific evidence. It is concluded that intraligamentary anaesthesia has a role to play in modern dental local anaesthesia but it does not fulfil all the requirements of a primary technique. PMID- 1452872 TI - Tooth wear and facial morphology. AB - This review sets out to explore the relationship between tooth wear and facial morphology, with particular reference to the occlusal vertical dimension. Evidence from anthropological and archaeological investigations suggests that severe tooth wear may not only affect the teeth and occlusion, but may also have more wide ranging effects on overall dentofacial morphology. Studies on contemporary subjects confirm this finding, and the literature on the nature of these effects is reviewed. It is concluded that the adult dentofacial complex is not a static entity, but can compensate for the dental effects of wear. The consequences of this with respect to reconstruction of the worn dentition are discussed, and it is proposed that the dynamic nature of this complex may be employed to help simplify the treatment of severe tooth wear. PMID- 1452873 TI - Titanium nitride coatings in clinical dentistry. AB - Titanium and its alloys are increasingly important in dentistry. Thin titanium nitride (TiN) coatings improve properties of metallic material for industrial purposes. Recently TiN coatings have been advocated in dentistry. In a survey of the literature, aspects of biological, mechanical and corrosive behaviour are assessed. Moreover, specific problems for clinical application are indicated. It is concluded that as long as the integrity of the TiN coating is not guaranteed under critical conditions, one should be cautious with its clinical application, and in no situation can it be used to improve deficient dental alloys. PMID- 1452874 TI - GDPs' and specialists' decisions in the management of fissure caries. AB - As part of a continuing education programme in dentistry, four specialists and 27 selected general dental practitioners were asked to rate 58 clinical management options relating to fissure caries in six simulated patient management problems called challenges. Their ratings are presented and the advantages and disadvantages of the approach are discussed. Areas of agreement and disagreement are highlighted and possible reasons for these explored. PMID- 1452875 TI - An analysis of multiple failures of resin-bonded bridges. AB - A clinical trial involving 203 resin-bonded bridges (RBBs) was undertaken to investigate the influence of several variables on the survival of these prostheses. This article presents the experiences with rebonded and replacement RBBs after failure of the originally bonded RBBs. A total of 62 dislodged and rebonded RBBs was included in this study and evaluated using Kaplan-Meier estimates. Rebonded RBBs that dislodged for a second time were replaced by another type of RBB ('replacement' RBBs, n = 32). The study revealed that rebonded RBBs were more susceptible to dislodgement than originally bonded RBBs. Fifty per cent survival was reached 2.1 years after rebonding. The sooner the first dislodgement occurred, the lower the retention rate of the rebonded RBB (PH model, beta = 0.78, P = 0.02). Also some failure characteristics were evaluated. Failure characteristics (i.e. fracture site and partial versus complete dislodgement) of first and second dislodgement were not correlated (Chi-square, P values > 0.25). The survival of 'replacement' RBBs was significantly better than the survival of multiply failure RBBs (median survivals respectively 1.6 years and 1.0 year, P = 0.03). From the results of this study it may be concluded that the survival rates of rebonded and replacement RBBs were unacceptable. PMID- 1452876 TI - In vivo confocal microscopy in clinical dental research: an initial appraisal. AB - Until recently, the in vivo microscopic investigation of intraoral tissues at high resolution has been virtually impossible. Confocal microscopy enables high resolution imaging to be achieved below semitransparent surfaces in intact living specimens, but this may still be impractical for intraoral applications because of the need to stabilize the sample. The development of a steadying objective (x 240 overall mag.) which is held against the sample surface and is focused by moving internal elements, avoids the need for fine adjustment of the living sample under the microscope to achieve a change of focus. It is therefore more comfortable and also reduces the problems of movement due to the pulse. The objective was used with a tandem scanning microscope, with images recorded via a SIT video camera. Using this system internal tooth structure (e.g. enamel prisms/adhesive restoration interfaces) and the lining cells of the gingival crevice through to the junctional epithelium may be examined. It is also possible to image the oral mucous membrane, focusing to the capillary loops in the basal layers, where streaming red blood cells can be seen. Access is limited to the anterior regions as far back as the premolar teeth. Applications could include caries research, soft and hard tissue responses to biomaterials (e.g. implants), wound healing and monitoring the effect of periodontal treatment regimens. This new technique offers numerous exciting opportunities for the microscopic investigation of many clinical operative procedures in vivo, allowing the response of the tissues to be non-destructively monitored, over time, at high resolution. PMID- 1452877 TI - Surface pH of resin-modified glass polyalkenoate (ionomer) cements. AB - The recently developed group of materials known as light-activated, or resin modified, glass polyalkenoate (ionomer) cements have been produced in response to clinical demands for a command set cavity base material. This study monitored the surface pH of three commercially available resin-modified glass ionomer cements over a 60-min period following either mixing alone or mixing followed by a 30-s exposure to a curing lamp. The results indicate that each material behaves in a unique manner. For all materials and conditions the pH reached after a 60-min period was significantly (P < 0.001) higher than the initial value. Light curing the materials significantly increased (P < 0.01) the surface pH of two of the materials (Baseline VLC and Vitrebond) as compared to the same materials in the uncured state. In the case of XR-Ionomer, however, no significant (P > 0.05) effect of light curing upon the surface pH was apparent. The precise clinical consequences of a low surface pH are unclear but may be an aetiological factor in postoperative pulpal sensitivity. It is therefore recommended that a sublining of a proprietary calcium hydroxide lining material should be placed routinely beneath these materials and every effort made to ensure effective light curing. PMID- 1452878 TI - Microleakage of three generically different fluoride-releasing liner/bases. AB - Three generically different fluoride-releasing materials that function as a liner or base were assessed for their microleakage performance on enamel and dentine. Group 1 (light-cured liner/base) showed much more leakage, but less bulk absorption of tracer, than Group 2 (traditional glass ionomer) or Group 3 (light cured glass ionomer). The response of the three materials to tracer penetration was consistent with what is known about their chemistry. The Group 2 and 3 materials are probably the materials of choice at the caries-vulnerable margins, which are not easily visible for inspection. PMID- 1452879 TI - Effect of the curing cycle on residual monomer levels of acrylic resin denture base polymers. AB - It has been shown previously that high levels of residual monomer have a deleterious effect on the properties of denture base polymers. Levels of residual monomer were determined on a homopolymer and a copolymer using gas-liquid chromatography. A wide range of recommended and 'short cut' curing cycles were then investigated which produced values ranging from 0.56 to 18.46%. From the ranges examined an optimum cycle of 7 h at 70 degrees C and 1 h at 100 degrees C was established which was used to polymerize 23 currently available synthetic denture base polymers. Only small differences were found between the materials tested with a range from 0.54 to 1.08% of residual monomer. PMID- 1452880 TI - Selection of dental procedures for antibiotic prophylaxis against infective endocarditis. AB - A dental source of infection remains the most common identifiable risk factor in infective endocarditis and this may be particularly important in patients at 'high risk'. We therefore performed a questionnaire survey of dental practitioners to assess acceptance of The British Society of Antimicrobial Chemotherapy (BSAC) recommendations, especially with regards to selection of dental procedures for antibiotic prophylaxis. The results showed that the dental practitioners surveyed treated the 'high risk' patient group differently by extending the range of dental procedures covered by antibiotics but the BSAC only recommend that they be treated differently by hospital treatment and/or parenteral antibiotics. This must be an area of concern and deserves further attention, especially with regards to the need for wider publicity and the range of dental procedures that should be covered in the 'high risk' group where morbidity and mortality from infective endocarditis are higher. PMID- 1452881 TI - Sources of error in gnathosonics. PMID- 1452882 TI - Periodontics: a practical approach. PMID- 1452883 TI - The fit of gold-alloy full-crown castings made with pre-wetted casting ring liners. AB - Measurements were made of the fit of full-crown gold-alloy castings produced with two types of pre-wetted ring liner (asbestos and cellulose) and a typical gypsum bonded investment (Cristobalite Inlay, Sybron/Kerr Products, Romulus, MI; W/P = 0.40). Laboratory measurements were made of the effects of the liners on potential investment expansion, and properties of the lining materials considered relevant to casting accuracy were also measured. There was a wide variation in values for mean dimensional inaccuracy. One liner produced a series of castings all of whose inaccuracies lay within the range +/- 0.1%, with a mean value of + 0.01%. With the other five liners, all or most castings were undersize. With three, all or most castings showed inaccuracies worse than -0.2%. The values for casting inaccuracy with the various liners showed a probable correlation with potential investment expansion (p < 0.05); however, no correlation was found between casting inaccuracy and any apparently relevant liner properties, alone or in combination. In casting techniques which use a pre-wetted ring liner, the choice of a specific lining material is an important factor which has a significant effect on casting inaccuracy. With at least three of the six liners tested, a higher investment expansion was needed for accurate full-crown castings to be ensured. PMID- 1452884 TI - The fit of gold-alloy full-crown castings made with ceramic casting ring liners. AB - Measurements were made of the fit of gold-alloy full-crown castings produced with dry ceramic ring liners. When used with vacuum investing, these liners absorb relatively large amounts of water from the investment mix (thereby reducing its original W/P ratio) and then function as wet liners, thus increasing the investment's potential expansion and giving castings which are consistently larger than when air investing is used. With four of the five liners tested, investing in air produced many castings which were unacceptably undersized (inaccuracy worse than -0.2%). The fifth liner, an industrial material 2 mm thick, gave only one casting out of 12 which was outside this limit, although all castings were undersized to a lesser extent. Vacuum investing gave improved casting accuracy; with four of the five liners, the improvement was highly significant (p < 0.001), and with the fifth, probably significant (p < 0.05). Even with vacuum investing, however, with only two of the liners did all castings show inaccuracies within +/- 0.2%. With the other three liners, some castings (ranging from 2/10 to 7/9) had inaccuracies worse than -0.2%. With both air and vacuum investing, changing from one liner to another caused changes in relative casting accuracy which were often significant (p < 0.01) or highly significant (p < 0.001). In casting techniques where a ceramic ring liner is used, the choice of specific lining material and the choice between investing in air or under vacuum are important factors which can have a major effect on the fit of castings. PMID- 1452885 TI - The effect of using layered specimens for determination of the compressive strength of glass-ionomer cements. AB - Compressive strength is widely used as the criterion of strength of glass-ionomer dental cements, despite the difficulties in interpretation of the findings. With the introduction of light-cured glass-ionomer cements, which can be used only in thin layers, the question arises of how test specimens should be prepared for the measurement of compressive strength. A suggested method has been to prepare test pieces by building them up in layers, an approach which is examined critically in the current paper. Two different conventional (acid-base) glass-ionomers were studied with the use of layered and unlayered specimens of dimensions 6 mm (height) x 4 mm (diameter) and 12 mm (height) x 6 mm (diameter). While smaller samples gave the same value of compressive strength as larger specimens, layered specimens gave significantly lower values of compressive strength for both sizes. In view of these findings, and since the layered specimens are tedious to prepare, we conclude that compressive strength is unsatisfactory as a criterion of strength for light-cured glass-ionomer cements. PMID- 1452886 TI - Association between salivary flow rate and the use of systemic medication among 76-, 81-, and 86-year-old inhabitants in Helsinki, Finland. AB - The aim of this study was to examine salivary flow rate and its association with the use of medication in a representative sample of 76-, 81-, and 86-year-old subjects, totaling 368. In this study, 23% (n = 80) of the subjects were unmedicated. From one to three daily medications were used by 47% (n = 168) and more than four medications by 30% (n = 104). The most commonly used medications were nitrates, digitalis or anti-arrhythmic drugs (47.7%), analgesics and antipyretics (32.6%), and diuretics (29.5%). The mean number used daily was significantly higher in 86-year-olds than in the two younger age groups (p < 0.01). No significant differences in this respect were found between genders. Among the unmedicated subjects, 76-year-olds had significantly higher stimulated salivary flow rates than did the 81-year-olds (p < 0.05). Unmedicated women showed significantly lower unstimulated (p < 0.01) and stimulated flow rates than did men (p < 0.05). Stimulated salivary flow rate was also significantly higher in the 76-year-old medicated subjects than in the medicated 86-year-old subjects (p < 0.05). No statistically significant differences were found in unstimulated salivary flow rates among the three age groups. Medicated women showed significantly lower unstimulated salivary flow rates than men (p < 0.001), although the difference in stimulated saliva flow was not significant. A statistically significant difference in unstimulated and stimulated salivary flow rates was found between unmedicated persons and those who took from four to six, or more than seven, prescribed medications daily. PMID- 1452887 TI - Immunocytochemical localization of cathepsins B and G in odontoclasts of human deciduous teeth. AB - For clarification of the mechanisms by which odontoclasts resorb deciduous teeth during physiological root resorption, cysteine-proteinases such as cathepsins B and G were immunocytochemically localized in odontoclasts at the ultrastructural level. Extracted human deciduous teeth undergoing root resorption were fixed with a mixture of formaldehyde and glutaraldehyde and processed for immunocytochemical detection of these enzymes. Sheep antisera, raised against either human cathepsin B or G, were used as primary antibodies. In odontoclasts, specific immunogold labeling of both anti-cathepsin B and G was clearly localized in lysosomes and pale vacuoles of various sizes, and in a portion of the extracellular canals of odontoclastic ruffled borders. In the presence of either antibody, the cytoplasmic matrix, mitochondria, and nuclei were minimally labeled by immunogold particles. The presence of these proteolytic enzymes in odontoclasts suggests that, during odontoclastic root resorption, these enzymes are involved in the formation of resorption lacunae by means of intra/extracellular degradation of collagen and other non-collagenous matrix proteins of deciduous teeth. PMID- 1452888 TI - Effects of sialagogues on ornithine decarboxylase induction and proto-oncogene expression in murine parotid gland. AB - The mechanism of a sialagogue-induced increase in ornithine decarboxylase (ODC) activity and the expressions of proto-oncogenes in murine parotid gland were investigated by use of isoproterenol (IPR), carbachol (CC), and methoxamine (MTX). The results were as follows: (1) The three sialagogues had similar effects on the parotid in vivo (mouse parotid after a single injection of IPR) and/or in vitro (rat parotid explants cultured on siliconized lens paper floating on 199 medium containing IPR, CC, or MTX), the order of their effectiveness being IPR > CC > MTX. (2) Northern/dot and Western blot analyses revealed that the sialagogues elevated the steady-state levels of ODC mRNA and ODC protein to maxima at two h and six h, respectively, after stimulation. The increases were roughly proportional to those in ODC activity, suggesting that sialagogue dependent enzyme induction is regulated at the transcriptional level. (3) The mRNAs of four of nine proto-oncogenes examined showed sialagogue-dependent increases to maxima at 30 min (c-fos) or 60 min (c-jun, c-myc, and c-src) after the beginning of stimulation. These increases were all transient, with the levels returning to the control values (without sialagogue) within 60 min. (4) The IPR dependent elevations of ODC activity and the mRNAs of ODC, c-fos, and c-jun were inhibited by monensin, but not by polymyxin B. On the other hand, the CC dependent increases in these parameters were inhibited by polymyxin B but not by monensin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452889 TI - Effect of age on immunoglobulin content and volume of human labial gland saliva. AB - Stimulated lower labial (LLGF) and parotid salivary volumes and IgG, IgA, and IgM concentrations were measured in 264 subjects whose ages ranged from 17 to 76 years. A significant (p < 0.001) age-related decline in LLGF output was observed for subjects over this age range. Sixty-three percent of the subjects in the 18 20-year-old group (n = 46) secreted at least 10 microL of labial saliva in a 7-10 minute period, while approximately 70% of the subjects in the two oldest groups (61-70 and 71-76 years old) secreted less than 1 microL of LLGF during this time period (n = 64). No significant gender-based differences occurred in the volumes of labial saliva secreted. Stimulated parotid salivary flow showed no age-related trend in these subjects. Lower labial gland salivary IgA concentrations in an older population (mean age +/- SD = 55.6 yr +/- 1.3) were significantly lower (p < 0.025) than IgA concentrations in a younger population (20.7 yr +/- 0.8), when IgA was expressed as microgram/mL LLGF collected. Immunoglobulin A concentrations in parotid saliva and IgG and IgM concentrations in labial and parotid saliva were not significantly different when the two age populations were compared. These data suggest that the physiological and immunological potential of labial gland saliva may decrease with age. PMID- 1452890 TI - The effect of chewing gum use on in situ enamel lesion remineralization. AB - Two independent cross-over studies investigated the possibility of enhanced early enamel lesion remineralization with the use of chewing gum. The first study involved a sorbitol-containing chewing gum, and the second, which had an identical protocol, tested a sucrose-containing chewing gum. In each study, 12 volunteers wore in situ appliances on which were mounted enamel sections containing artificial caries lesions. Subjects brushed twice daily for two min with a 1100-ppm-F (NaF) dentifrice (control and test) and in the test phase chewed five sticks of gum per day for 20 min after meals and snacks. Microradiographs of the enamel lesions were made at baseline and at the end of the seven-week experimental period. In the sugar-free gum study, the weighted mean total mineral loss (delta z) difference [(wk7-wk0) x (-1)] was 788 vol.% min. x micron for the gum, corresponding to remineralization of 18.2%, vs. the control value of 526 vol.% min. x micron, 12.1% remineralization (p = 0.07). There were no significant differences for the surface-zone (p = 0.20) and lesion body (p = 0.28) values. In the sucrose-containing gum study, the delta z difference was 743 vol.% min. x micron for the gum, corresponding to a remineralization of 18.3%, vs. the control value of 438 vol.% min. x micron, 10.8% remineralization (p = 0.08). The surface-zone values were not significantly different (p = 0.55). For the lesion body, however, the sucrose-containing gum value of 6.11 vol.% min. was significantly different (p = 0.01) from that of the control (2.81 vol.% min.). PMID- 1452891 TI - Characterization of fibroblast clones from periodontal granulation tissue in vitro. AB - Connective tissues are known to be composed of heterogeneous fibroblast subpopulations. The significance of this heterogeneity in different physiological and pathological conditions is poorly understood. Granulation tissue is formed in connective tissue during wound healing, chronic inflammation, and certain pathological conditions. In this study, heterogeneity of fibroblasts from granulation tissue was investigated by cell-cloning techniques. Granulation tissue fibroblasts (GTFs) from both chronically inflamed periodontal lesions and healing wound granulation tissue behaved similarly. GTFs showed a more pronounced decrease in proliferative capacity with increasing cumulative population doubling levels (CPDLs) and 30-40% lower cloning efficiency compared with normal gingival fibroblasts (HGFs). Morphologically, cells in GTF cultures were mainly large, whereas HGFs were mainly small in size. Both cell-line types showed heterogeneity in cell morphology. Clones composed of large stellate-like cells predominated in GTF cultures, whereas clones composed of small spindle-shaped or epithelioid cells predominated in HGF cultures. In both cell-line type the proportion of clones composed of large cells increased without increasing CPDL. These findings show that the properties of the fibroblasts changed during their in vitro life spans. The finding that normal connective tissue and granulation tissues contain morphologically distinct fibroblast clones in different proportions suggests that local factors could stimulate local fibroblasts to differentiate into GTFs. Alternatively, local factors could select some fibroblast subpopulations to overgrow the others to form granulation tissue. PMID- 1452892 TI - Histomorphometric study of the periodontal vasculature of the rat incisor. AB - This study assessed quantitatively the vascular system in the cementum-related periodontal ligament (PDL) along the rat incisor. The lower left incisors of six rats (+/- 200 g) were subjected to routine histological procedures and cross sectioned serially (2 microns), and the distance between each section and the apex was computed. The PDL of five sections at different levels along the tooth was divided into mesial, lingual, and lateral parts. The number and area of small and terminal arterioles, capillaries (C), sinusoids (S), post-capillary venules (PCV), and connecting venules, as well as the area of the PDL, were established. Blood vessels (BV) occupied 47 +/- 2% of the PDL area in the apical half and 4 +/ 2% at the incisal end. Of the total BV area, 41%, 32%, and 27% were located on the lingual, mesial, and lateral tooth sides, respectively. The majority of BV belonged to the venous system (98.5 +/- 0.6% and 82.5 +/- 3.0% in the apical and incisal parts, respectively). The apical venous system comprised 95.4 +/- 1.6% S and 3.2 +/- 1.0% PCV, reversing to 27.2 +/- 14.2% S and 55.2 +/- 11.3% PCV in the incisal half. The number of arterial profiles increased gradually from 6.8 +/- 1.5 at the apex to 25.3 +/- 2.4 in the incisal part and that of C from 9.0 +/- 1.18 to 25.0 +/- 4.3. The extensive vascularization in the apical half of the PDL is consistent with the high metabolic demands and with the need for protective cushioning of the constantly growing dental and periodontal tissues.2+_ PMID- 1452893 TI - The vascularity of dental pulp in cats. AB - The fraction of the volume of the coronal pulp of cat canines that is occupied by blood vessels was estimated by measurement of the cross-sectional areas of all the vessels in a complete transverse section of the pulp from each of four teeth. The sections were taken 0.5 mm from the pulp cornu. Overall, 14.4% of the area of the pulp was occupied by vessels. In the core of the pulp, the average value was 42.9%, and superficially, near the odontoblast layer, it was between 5 and 10%. The average capillary density was 1402/mm2, which is higher than in most other tissues. Laser Doppler flow meters can be used for recording blood flow from the coronal pulp of intact teeth, but these instruments are linear only if the moving blood cells occupy no more than 1% of the tissue volume. The present results suggest that this figure is exceeded in pulp. PMID- 1452894 TI - Suppressor cell function in oral lichen planus. AB - Oral lichen planus (OLP) is a common inflammatory condition of the oral mucous membranes which affects between one and two percent of the general population. In accordance with the protracted clinical course of OLP and its association with known auto-immune diseases, the level of self-tolerance is questionable and possibly diminished in patients with this disorder. Normal suppressor T lymphocyte function is reputedly an essential element in the maintenance of self tolerance, and deficient cell-mediated suppressor activity is implicated in the pathogenesis of auto-immune diseases. For assessment of in vitro cell-mediated suppressor activity in OLP, peripheral blood mononuclear cells (PBMC) from ten patients with OLP and from 11 control subjects were activated with the plant mitogen concanavalin A (Con A), followed by co-culture with autologous responder cells. The ability of irradiated Con A-activated cells to suppress the proliferation of Con A-stimulated responder cells was determined. Con A-induced suppressor activity of PBMC in the OLP patients was significantly less than that in control subjects (p = 0.001). Results of the present investigation complement previous in vitro findings which provided indirect evidence of deficient cell mediated suppressor activity in OLP, particularly a decreased proportion of circulating CD4+CD45RA+ lymphocytes and reduced Con A-stimulated PBMC proliferation. The depressed Con A-induced suppressor activity of PBMC in the OLP patients provides direct evidence of deficient in vitro cell-mediated suppressor function in OLP, and suggests that defective cell-mediated suppressor circuits and reduced self-tolerance may be involved in the pathogenesis of this disorder. PMID- 1452895 TI - Effect of a pulsing electromagnetic field on demineralized bone-matrix-induced bone formation in a bony defect in the premaxilla of rats. AB - A 2-mm non-healing bony defect was prepared in the premaxilla of male Wistar rats weighing about 180 g as a simulation of an alveolar cleft, for determination of whether a pulsing electromagnetic field (PEMF) could promote regeneration of bone induced by demineralized bone matrix (DBM). The defect was either treated with 7 mg DBM or was left as a non-grafted control. The rats were exposed to a PEMF with a frequency of 100 Hz, a 10-ms-wide burst with 100 microseconds-wide quasi rectangular pulses, repeating at 15 Hz, and magnetic field strength of 1.5-1.8 G. Alkaline phosphatase activity increased significantly from day 7 in the DBM-graft plus-PEMF group and from day 10 in the DBM-graft group, reaching a maximum on day 14. A greater-than-two-fold rise in alkaline phosphatase activity and a three fold rise in the amount of 45Ca incorporation in the DBM-graft-plus-PEMF group were attained compared with those of the DBM-graft group. The DBM-graft-plus-PEMF group produced more bone with almost complete osseous bridging in the defect sites than did the group treated with DBM only on day 35. The findings indicate that PEMF had an enhancing effect on the bone-inductive properties of the DBM through the stimulation of osteoblast differentiation induced by DBM. PMID- 1452896 TI - Dental predictors of high caries increment in children. AB - A comprehensive set of dental variables was investigated to find the "best" combination of predictors for high caries increment in 7/8-year-old and 10/11 year-old children. Four populations with widely different caries prevalence were studied. Logistic regression analysis supplied multiple-input models by stepwise selection of predictors. A "low number of sound primary molars" was the best and most consistent predictor of high caries increment. The second best predictors were "high numbers of pre-cavity lesions on permanent first molars" (discolored pits and fissures in the younger age group and white spots on the smooth parts of buccolingual surfaces in the older age group). Inclusion of radiological variables did not substantially increase the quality of prediction. For practical application, models with various multiple inputs selected by stepwise procedures were compared with "fixed" three-input models. These three-input models resulted in predictive quality nearly equal to those of the multiple models. Traditional one-input models, containing DMFT or dmft, were inferior to the three-input models, particularly in the older age class. The lower the caries prevalence of the source data, the better was the prediction. As a summary measure characterizing the predictive performance of a model, we used the index "area under the receiver operating characteristic curve" A. For the 1984 data and the three-input models, the area was approximately 80%, and for the 1972 data, the area was 65-70%. PMID- 1452897 TI - Accuracy of visual inspection, fiber-optic transillumination, and various radiographic image modalities for the detection of occlusal caries in extracted non-cavitated teeth. AB - Occlusal caries lesions may progress into the dentin without this resulting in a macroscopic breakdown of the enamel surface. Imaging methods may therefore be needed to aid in the visual detection of occlusal caries. It was the aim of this study to evaluate diagnostic accuracy in a laboratory set-up of visual inspection (VI), fiber-optic-transillumination (FOTI), conventional radiography (CR), and two digital radiographic image modalities (DRm and DRr) for detection of occlusal caries in clinically non-cavitated teeth. Eighty-one extracted third molars from 18-20-year-old males were assessed by four observers on a five-rank confidence scale by the five methods. Ground sections (500-600 microns) served as validation for true state of disease: 1 = no caries in dentin, 2 = caries just beyond dentino-enamel junction, or 3 = deep dentinal caries, halfway or more to the pulp. ROC analysis was performed on the basis of the confidence rank scale data on two diagnostic thresholds, T1 = caries in dentin (disease state 2+3) and T2 = caries deep in dentin (state 3). On the T1 level, use of the FOTI method gave on average the most accurate diagnosis, closely followed by VI, both performing better than use of radiography. On the T2 level, all five diagnostic methods performed equally well. PMID- 1452898 TI - Robustness of the t test applied to data distorted from normality by floor effects. AB - In calculus, plaque, and gingivitis trials, measures are taken on subjects both prior to the use of an active treatment and after its use. When the trial is short-term, or when a cleaning of the mouth takes place after the baseline measurement, distributions of such measures (e.g., the Volpe-Manhold score or the Loe and Silness scale) are approximately normally distributed above zero but also can have a proportion of subjects who attain scores of zero. When the effects of an active treatment are compared with those of a control, the two-independent sample t test can be applied to outcome scores or to differences between the baseline and outcome scores. Robustness of these t tests, in the presence of distributions "distorted" from normality as described, was investigated by computer simulation. In general, both t tests produced actual significance levels which were close to nominal significance levels, even in the presence of small samples and distributions in which as many as 50% of the subjects attained scores of zero. PMID- 1452899 TI - Dentistry--some thoughts for the future. PMID- 1452900 TI - [The action of low doses of nitrosomethylurea on a stationary cell population. An experiment and modelling]. AB - The change of stationary cell population (murine spleen) following an exposure to low doses of methylnitrosourea (10(-11)-10(-5) g/kg of mouse weight) was investigated and modelled mathematically. The suggested model is based on the idea that the effect of cytotoxic agent in low doses has nondestructive "signal" character, changing dynamic balance between cells in proliferating and quiescent compartments. PMID- 1452901 TI - [The effectiveness of ultralow doses and concentrations of biologically active compounds]. AB - Numerous data of literature are analysed on the biological activity of ultra-low (10(-12)-10(-19) M) concentrations and corresponding doses of same bioregulators. Our own data are presented on the modulation of lymphatic vessel contractility by peptides (thyroliberin, defensin, and tuftsin) in concentrations ranging from 10( 13) to 10(-16) M. Hypothetic mechanisms of these phenomena are discussed. PMID- 1452902 TI - [The MB1 family of repeats in clones from the genomes of mammals]. AB - Members of MB1 family repeats are revealed in genomes of many mammals (cow, rabbit, opossum, horse, ...). The MB1 repeats from cow and rabbit genomes are mirror-reflected about the SINE families repeats from cow and rabbit genomes. The life time of MB1 repeats are no less than 100 million years. Classification of MB1 repeats from human genome using the information similarity was performed. This classification has revealed two subfamily MB1 repeats in human genome. Possible processes of creation of MB1 family repeats common for many mammals are discussed. PMID- 1452903 TI - [The suppression of the chemiluminescence of mammalian cells by the metabolites of Crithidia oncopelti]. AB - Effect of water-soluble (polypeptides) fraction (PF) of Crithidia oncopelti on the chemiluminescence of human blood cells and murine splenocytes was studied. The study has shown that PF possessed a capacity to inhibit oxygen-dependent killer system of polymorphonuclear leucocytes in dose-dependent manner. This effect was of a complex nature. The inhibitory effect of PF was demonstrated also in respect to murine mononuclear phagocytes and splenocytes. It was suggested that, in this case, the suppressor effect was related with the influence on membranous cytokines. PMID- 1452904 TI - [The systems-related preconditions of aging]. PMID- 1452905 TI - [The adaptational-regulatory theory of age-related development]. PMID- 1452906 TI - [The physiological mechanisms of aging and research on age-related mortality]. PMID- 1452907 TI - [Experimental approaches to elucidating the patterns of the aging of the body]. PMID- 1452908 TI - [The impossibility in principle of an appreciable increase in the life expectancy of the human species]. PMID- 1452909 TI - [Aging is a result of a shortening of the "differotene" in the telomere due to end under-replication and under-repair of DNA]. PMID- 1452910 TI - [Aging and the immortalization of animal cells: the key role of nuclear proto oncogenes]. PMID- 1452911 TI - [The trigger of the aging process--in the nucleus or the mitochondria?]. PMID- 1452912 TI - [The bioenergetic aspects of the mechanism of aging]. PMID- 1452913 TI - [The mitochondrial theory of aging]. PMID- 1452914 TI - Papillon-Lefevre syndrome. AB - Papillon-Lefevre syndrome, also known as hyperkeratosis palmaris et plantaris or hyperkeratosis palmoplantaris, is a devastating dermatological disease characterized by a thickening of the stratum corneum of the skin on the palms of the hands and soles of the feet. In addition, some patients manifest excessive sweating (hyperhidrosis), the growth of fine body hair and the development of dirty-colored skin on the affected parts. Calcification of the falx cerebri of the dura mater, as well as other areas of the brain, have been reported. From a dental standpoint, young patients with Papillon-Lefevre syndrome have juvenile or precocious periodontosis, with severe destruction of the alveolar bone in both deciduous and permanent dentitions. Bone loss has been observed as early as two years of age, with premature exfoliation of the teeth. There is usually gingival enlargement, gingival ulceration and the formation of deep periodontal pockets; but in some cases, there is no inflammatory reaction and only the periodontium of the secondary teeth is affected. This disease eludes all known forms of therapy and results in edentulousness after only a few years. PMID- 1452915 TI - Advertising and the dental profession. Retrospective and prospective. AB - "Advertising" has become a very controversial topic, not just among dentists, but among all professionals. That controversy focuses on three questions. First, what are the legal issues surrounding dental advertising and how are these issues being resolved? Second, what are the attitudes toward advertising among practicing dentists and how are these attitudes changing? Finally, how many dentists advertise and what are those advertising dentists actually doing? The purpose of this paper is to neither praise nor excoriate advertising, but to refer to the law and to published research in order to provide dental practitioners with a broader understanding of this topic. PMID- 1452916 TI - Invasive versus conservative strategy after thrombolytic therapy for acute myocardial infarction in patients with antecedent angina. A report from Thrombolysis in Myocardial Infarction Phase II (TIMI II). AB - OBJECTIVES: This study was designed to assess the possibility that a subgroup of patients at high risk for recurrent ischemia and reinfarction after thrombolytic therapy might benefit from early intervention. BACKGROUND: The Thrombolysis in Myocardial Infarction Phase II (TIMI II) study recently concluded that an obligatory invasive strategy after thrombolytic therapy offered no advantage over a more conservative strategy. METHODS: Data from the 3,534 patients enrolled in the TIMI II trial were analyzed to determine whether a history of antecedent angina before myocardial infarction identifies patients at high risk for subsequent ischemia and whether these patients might benefit from an invasive strategy. RESULTS: Within the TIMI II population, antecedent angina identified patients at increased risk for recurrent chest pain in the hospital (32.3% vs. 22.1%, p < 0.001) and recurrent infarction during the 1st year of follow-up (11.2% vs. 7.9%, p = 0.001) compared with that of patients without antecedent angina. Among patients assigned to the invasive strategy, coronary arteriography revealed that those with antecedent angina had a more severe residual stenosis of the infarct-related artery after thrombolytic therapy (77.1 +/- 0.7% vs. 73.0 +/- 0.9%, p < 0.001) and more multivessel disease (37.9% vs. 26.4%, p < 0.001). The clinical outcome of the patients with antecedent angina assigned randomly to either the invasive or the conservative strategy were compared. The invasive strategy patients had a slightly lesser incidence of recurrent chest pain in the hospital (29.9% vs. 34.8%, p = 0.13) and more negative (normal) findings on exercise tolerance tests (24.7 vs. 18.9%, p = 0.003), but there was no difference between the treatment strategies in the end point variable of recurrent myocardial infarction or death. CONCLUSIONS: These data demonstrate that antecedent angina identifies patients at increased risk for recurrent ischemic events after thrombolytic therapy. However, similar to the results for the overall population, the invasive strategy does not alter the risk of reinfarction or death compared with the conservative approach. PMID- 1452917 TI - Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction trials. AB - OBJECTIVES: The aim of this study was to determine whether streptokinase treatment improves long-term survival in patients with acute myocardial infarction. BACKGROUND: Thrombolytic treatment for acute myocardial infarction reduces early mortality and improves the 1-year survival rate, but the long-term (3 to 8 years) survival benefits of treatment and the relation between survival and baseline clinical characteristics, infarct size and ventricular function have not been established. METHODS: We assessed survival status at a minimum of 3 and a mean of 4.9 +/- 2.3 years in 618 patients randomized between 1981 and 1986 to receive conventional treatment (n = 293) or thrombolysis with streptokinase (n = 325) in the Western Washington Intracoronary (n = 250) and Intravenous (n = 368) Streptokinase in Myocardial Infarction trials. The relation between long-term survival and thrombolytic treatment, admission baseline clinical characteristics and late radionuclide tomographic thallium-201 infarct size and ejection fraction was assessed in a subset of patients. RESULTS: Survival at 6 weeks was 94% in patients who received streptokinase versus 88% in the control group (p = 0.01). However, survival at 3 years was 84% in the streptokinase group and 82% in the control group and for the total period of follow-up, there was no significant survival benefit (p = 0.16). Analysis by infarct location showed a higher survival rate at 3 years for patients treated with anterior infarction (76% vs. 67% for the control group), but no overall survival benefit (p = 0.14). Survival at 3 years for patients with an inferior infarction was 89% in the streptokinase group and 91% in the control group (p = 0.62). By stepwise Cox regression analysis, admission clinical variables associated with decreased long-term survival were anterior infarction, advanced age, history of prior infarction and the presence of pulmonary edema or hypotension. Although streptokinase therapy was associated with improved survival, it was not an independent determinant of survival (p = 0.069). Ejection fraction and thallium-201 infarct size measured approximately 8 weeks after enrollment had a strong association with long-term survival. Univariate analysis in a subgroup of 289 patients with complete data selected infarct size, ejection fraction, age and history of prior infarction as predictors of survival. In the multivariate model, only ejection fraction (p < 0.0001), age (p = 0.008) and prior myocardial infarction (p = 0.02) remained strong predictors. CONCLUSIONS: In these early trials of thrombolytic therapy for acute myocardial infarction, streptokinase improved early survival, but there was little long-term survival benefit. This failure to show an improvement in the 3- to 8-year survival rate may also reflect the need to study a larger group of patients or to initiate treatment earlier after symptom onset. PMID- 1452918 TI - Additional ST segment elevation during the first hour of thrombolytic therapy: an electrocardiographic sign predicting a favorable clinical outcome. AB - OBJECTIVES: The aim of this study was to investigate the significance of further ST elevation that occurs during the 1st h of thrombolytic therapy before the expected resolution. BACKGROUND: Early resolution of ST segment elevation is commonly accepted as a marker of clinical reperfusion during thrombolytic therapy for acute myocardial infarction. Using frequent electrocardiographic recordings, we observed in some patients further ST elevation that occurred during hour 1 of thrombolysis before the expected resolution. METHODS: To investigate the significance of this pattern, we classified 177 consecutive patients with a first acute myocardial infarction into two groups: Group A, 98 patients with ST elevation > or = 1 mm above the initial ST elevation during the 1st h of thrombolytic therapy, and Group B, 79 patients without this finding. RESULTS: Although the presence or absence of additional ST elevation was not associated with a clinical or prognostic difference in patients with a first inferior or posterior acute myocardial infarction, its presence indicated a more favorable clinical outcome and prognosis in patients with anterior infarction. Among the patients with anterior infarction the 65 patients in Group A had a higher ejection fraction (44 +/- 9% vs. 35 +/- 11%, p < 0.01), less heart failure (15% vs. 35%, p = 0.02) and a lower in-hospital mortality rate (0% vs. 8%, p = 0.04) than did the 37 patients from Group B. CONCLUSIONS: Additional ST elevation early during thrombolytic therapy in patients with anterior infarction suggests a favorable clinical outcome and thus may be indicative of successful reperfusion. PMID- 1452919 TI - Relation of deep arterial resection and coronary artery aneurysms after directional coronary atherectomy. AB - OBJECTIVES: The aims of this study were to document the frequency of coronary artery aneurysm formation in patients undergoing directional coronary atherectomy and to determine the relation of such aneurysms to the depth of arterial resection. BACKGROUND: Deep arterial injury is relatively frequent with the use of directional coronary atherectomy, but the potential for subsequent coronary artery aneurysm formation is unknown. METHODS: Results in a consecutive series of 64 successfully treated patients (a total of 69 lesions; mean angiographic follow up at 5 months) treated with directional coronary atherectomy were retrospectively analyzed with use of quantitative angiographic and histologic data. RESULTS: Coronary aneurysms (ratio of dilated vessel segment to the adjacent reference segment > 1.2:1) occurred in seven patients (10%). The only significant clinical correlate of aneurysm formation was a relatively shorter duration of angina. There were no significant preprocedural angiographic predictors of aneurysms, although 6 (86%) of the 7 aneurysmal lesions arose from restenosis lesions compared with 30 (48%) of 62 lesions with no subsequent aneurysm development (p = 0.06). Histopathologic examination of 414 specimens from 68 treated lesions showed no significant difference in the occurrence of subintimal resection (media +/- adventitia) between those with and without subsequent aneurysm (29% vs. 22%). Media alone was found in 14% of specimens from lesions that later became aneurysmal versus 15% of those that did not; adventitial resection was found in 14% and 7% of specimens, respectively (p = 0.08), with relatively more adventitia per specimen from those with aneurysm (55% vs. 30% without aneurysm, p = 0.08). CONCLUSIONS: Aneurysms occur relatively frequently after directional coronary atherectomy. Although there was no statistically significant correlation with the depth of arterial resection, the evidence from this study suggests that the role of adventitial resection in the occurrence of late aneurysm development should be explored further. PMID- 1452920 TI - Prognosis in cardiogenic shock after acute myocardial infarction in the interventional era. AB - OBJECTIVES: The purpose of this study is to describe the outcome in cardiogenic shock treated with aggressive reperfusion therapy and to identify factors predictive of in-hospital and long-term mortality. BACKGROUND: Cardiogenic shock is the most common cause of death in patients admitted to the coronary care unit. Although studies have reported lower mortality rates in shock treated with angioplasty, few studies have described a cohort of patients with shock who were not selected because they were most likely to benefit from reperfusion therapy. METHODS: A consecutive series of 200 patients admitted with acute myocardial infarction complicated by cardiogenic shock were studied. RESULTS: The in hospital mortality rate was 53%. Variables with significant univariable association with in-hospital death included patency of the infarct-related artery, patient age, lowest cardiac index, highest arteriovenous oxygen difference and left main coronary artery disease. The most important independent predictors of in-hospital death were patency of the infarct-related artery, cardiac index and peak creatine kinase, MB fraction. The mortality rate in patients with patent infarct-related arteries was 33% versus 75% in those with closed arteries and 84% in those in whom arterial patency was unknown. Patients who survived to hospital discharge were followed up for a median of 2 years, with a mortality rate of 18% after 1 year. The best descriptors of the relation between these variables and postdischarge mortality included age, peak creatine kinase, ejection fraction and patency of the infarct-related artery. CONCLUSIONS: In a large consecutive series of patients with cardiogenic shock with complete follow-up, patency of the infarct-related artery was most strongly associated with in-hospital and long-term mortality. This finding supports an aggressive interventional strategy in patients with cardiogenic shock. PMID- 1452921 TI - Effects of acute, transient coronary occlusion on global and regional right ventricular function in humans. AB - OBJECTIVES: The aim of this study was to investigate the changes in right ventricular function during acute coronary occlusion produced by inflating a coronary angioplasty balloon catheter. BACKGROUND: Alterations in right ventricular function are well known to occur in patients with acute myocardial infarction or ischemic cardiomyopathy. However, the changes in right ventricular function resulting from acute, transient coronary occlusion of each of the major coronary arteries have been scantily studied, perhaps because of serious limitations of currently available technology. METHODS: A newly designed, mobile, multiwire gamma camera, in combination with generator-produced tantalum-178, affords high count rate first-pass radionuclide angiography and is thus ideal for studying right ventricular function at the bedside. Accordingly, 46 patients underwent first-pass radionuclide angiography at baseline and during transient coronary occlusion induced by a coronary angioplasty balloon catheter. RESULTS: A significant, albeit modest, decrease in global right ventricular ejection fraction occurred during occlusion of the left anterior descending (from 42.9 +/- 9.3% to 39 +/- 8.7%, p < 0.05) and left circumflex (from 44 +/- 9.1% to 38.8 +/- 7.9%, p = 0.03) coronary arteries, but diagonal artery occlusion caused no significant change in right ventricular ejection fraction. Occlusion of the right coronary artery proximal (but not distal) to the acute marginal branch caused a significant decrease in right ventricular ejection fraction (from 42.6 +/- 4.7% to 35.7 +/- 7.2%, p < 0.01). Although occlusion of the left anterior descending, left circumflex and proximal right coronary arteries all caused significant deterioration in regional right ventricular function, only proximal right coronary occlusion caused right ventricular dilation (p < 0.005). CONCLUSIONS: Significant impairment of right ventricular function occurs during transient occlusion of the left anterior descending, left circumflex and proximal right coronary arteries, but only occlusion of the latter causes acute right ventricular dilation, probably as a result of ischemia. PMID- 1452922 TI - Relation between stimulation site of cardiac afferent nerves by adenosine and distribution of cardiac pain: results of a study in patients with stable angina. AB - OBJECTIVES: The purpose of this study was to establish whether stimulation of cardiac sensory receptors in different myocardial regions results in different distributions of cardiac pain. BACKGROUND: Previous studies have shown that adenosine provokes cardiac pain through stimulation of sensory receptors in the absence of myocardial ischemia. In this study adenosine was used to obtain a regional stimulation of cardiac sensory receptors. METHODS: Increasing doses of adenosine (0.25, 0.5 and 1 mg/min) were selectively infused into the right and then into the left coronary artery in 26 patients with stable angina. RESULTS: No patient developed ischemic electrocardiographic changes during either adenosine infusion. Eighteen patients experienced cardiac pain during both infusions. Despite the stimulation of sensory receptors in different myocardial regions, 13 patients experienced cardiac pain in the same body area. Adenosine-induced pain was always similar to the anginal pain. By contrast, the remaining five patients experienced adenosine-induced cardiac pain in different body areas. In two of these patients, the distribution of anginal pain was similar to that experienced during one of the two adenosine infusions. In the remaining three patients, the distribution of anginal pain was similar to that experienced during adenosine infusion into the right coronary artery during some anginal episodes and to that experienced during adenosine infusion into the left coronary artery during other episodes. CONCLUSIONS: During stimulation by adenosine of sensory receptors in different myocardial regions, the majority of patients experience cardiac pain in the same body area; only a few experience pain in different areas. These differences might be caused by different organizations of the ascending neural pathways to the cortex. Our results suggest that in the same patient different distributions of pain during anginal attacks are probably due to ischemia in different myocardial regions. PMID- 1452923 TI - Comparison of transthoracic and transesophageal echocardiography in evaluation of 47 Starr-Edwards prosthetic valves. AB - OBJECTIVES: Our objectives were to characterize by transesophageal echocardiography the normal appearance of the Starr-Edwards prosthetic heart valve and to compare the utility of transesophageal and transthoracic echocardiography in detection of valve abnormality. BACKGROUND: The Starr-Edwards prosthetic heart valve, the first mechanical valve to be used, has demonstrated excellent durability. METHODS: Fifty transthoracic and transesophageal echocardiographic studies on 37 patients with 47 Starr-Edwards prosthetic valves were analyzed retrospectively. Six cases of surgically confirmed infective endocarditis were studied. RESULTS: Vegetation or abscess formation, or both, was identified by transesophageal echocardiography in all six cases of infective endocarditis but was found in only one of these cases by transthoracic echocardiography. Thrombus was detected by transesophageal echocardiography in 9 of 11 patients with transient ischemic attacks or stroke and in 2 patients by transthoracic echocardiography with 3 confirmed at surgery. In 26 of the 30 patients with a mitral Starr-Edwards valve, the valve demonstrated a trivial or mild "closing volume" early systolic or holosystolic leak on transesophageal echocardiography alone. Transthoracic evaluation identified significant mitral regurgitation in six of the eight patients who had this finding on transesophageal echocardiography. Serial studies were performed to assess response to treatment or need for surgical intervention in eight patients. Seventeen valves have been implanted for 12 years; six of these had significant leakage without apparent cause, a finding not observed more recently implanted valves. CONCLUSIONS: These observations demonstrated the unique utility of transesophageal echocardiography in patients with Starr-Edwards prosthetic valve dysfunction, endocarditis or thrombus formation, and of the clear superiority of transesophageal echocardiography over transthoracic echocardiography in these situations. PMID- 1452924 TI - Aortic valve replacement in octogenarians with aortic stenosis: a case-control study. AB - OBJECTIVES: This study was designed to compare the results of aortic valve replacement in patients greater than or equal to 80 years old with those in patients 65 to 75 years old. BACKGROUND: Aortic valve replacement may be potentially more complicated and require the use of more resources when performed in octogenarians rather than in younger patients. Few hard data on this possibility are available. METHODS: The study group comprises all 44 patients greater than or equal to 80 years old (mean age 82 years) who underwent aortic valve replacement at our institution between January 1981 and July 1989. A control group of 83 patients with a mean age of 70 years was matched with the study group for gender and approximate date of valve replacement. Before operation, 86% of the older patients versus 36% of the younger patients were in New York Heart Association functional class III or IV (p less than 0.001). Data were retrospectively collected from hospital records and a self-assessment telephone interview was conducted. RESULTS: The early mortality rate was 14% in the older group versus 4% in the younger group (p = 0.045). The duration of respirator support, intensive care and the total duration of the hospital stay did not differ significantly between groups. The incidence of postoperative low cardiac output syndrome was higher in the older group (p = 0.049), but the incidence of late valve-related complications was similar in the two groups. The 2-year survival rate (including data on patients who died early) was 73% in the older group and 90% in the younger group (p = NS). Six months postoperatively all patients but one were in functional class I or II. CONCLUSIONS: Although the patients greater than or equal to 80 years old had a poorer preoperative status than that of younger patients, aortic valve replacement in this group did not require more use of hospital resources and resulted in a clinical improvement comparable to that of younger patients. PMID- 1452925 TI - Aortic valve resistance as an adjunct to the Gorlin formula in assessing the severity of aortic stenosis in symptomatic patients. AB - OBJECTIVES: This study was conducted to determine the utility of aortic valve resistance in assessing the severity of aortic stenosis. BACKGROUND: Assessment of the severity of aortic stenosis has traditionally employed hemodynamic data and the Gorlin formula to calculate the area of the aortic valve. Recently, flow dependence of the Gorlin formula has been identified and the accuracy of the formula challenged. Aortic valve resistance, the quotient of gradient and cardiac output, has been advanced as potentially useful in assessing the severity of valve stenosis. METHODS: We studied 48 symptomatic patients with an initial diagnosis of severe aortic stenosis based on a calculated aortic valve area of less than or equal to 0.8 cm2 by the Gorlin formula. Forty of these patients (Group I) were confirmed to have severe aortic stenosis, whereas 8 (Group II) were subsequently proved not to have severe aortic stenosis. The 18 patients in Group I with a valve area of 0.6 to 0.8 cm2 (Group IA) were directly compared with Group II patients who had a similar valve area. RESULTS: Aortic valve area was nearly identical in Group IA and Group II patients (0.69 +/- 0.05 and 0.71 +/ 0.06 cm2, respectively, p = NS). However, aortic valve resistance was much less in Group II patients (212 +/- 6 vs. 316 +/- 11 dynes.s.cm-5, p less than 0.0001). In this small cohort, aortic valve resistance achieved nearly complete separation of patients in Groups IA and II. CONCLUSIONS: In some patients with relatively mild aortic stenosis, the calculated valve area may indicate that the stenosis is severe. The use of aortic valve resistance in conjunction with the Gorlin formula helps separate patients with truly severe aortic stenosis from those with milder disease. PMID- 1452926 TI - Diastolic function of the nonfilling human left ventricle. AB - OBJECTIVES: To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice. BACKGROUND: When mitral inflow was impeded in anesthetized dogs, left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect. METHODS: Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon. RESULTS: The left ventricular diastolic asymptote pressure (P(asy)) was determined in 47 nonfilling beats with a sufficiently long (greater than 200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 +/- 3 mm Hg for beats with normal intraventricular conduction and 3 +/- 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 +/- 14 ml and was comparable to the left ventricular end-systolic volume (39 +/- 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval greater than 200 ms, normal intraventricular conduction and peak left ventricular pressure greater than 50 mm Hg. Time constants (T0 and TBF) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a time constant (T(asy)) derived from an exponential curve fit with the measured diastolic left ventricular asymptote pressure. The value for T(asy) (37 +/- 9 ms) was significantly smaller than that for TBF (68 +/- 28 ms, p less than 0.001) and the value for the measured diastolic left ventricular asymptote pressure (2 +/- 4 mm Hg) was significantly larger than that for the best-fit asymptote pressure (-9 +/- 11 mm Hg, p less than 0.001). T0 (44 +/- 20 ms) was significantly (p less than 0.01) different from TBF but not from T(asy). CONCLUSIONS: During balloon inflation of a self-positioning Inoue balloon, left ventricular pressure decayed continuously toward a positive asymptote value and left ventricular cavity volume was comparable to the left ventricular end-systolic volume of filling beats. In these nonfilling beats, the best-fit asymptote pressure was unrelated to the measured asymptote pressure and T0 was a better measure of T(asy) than was TBF. Reduced internal myocardial restoring forces, caused by different extracellular matrix of the human heart, reduced external myocardial restoring forces caused by low coronary perfusion pressure during the balloon inflation and inward motion of the balloon-occluded mitral valve into the left ventricular cavity could explain the failure to observe significant diastolic left ventricular suction in the human heart. PMID- 1452927 TI - Quantitation of chronotropic response: comparison of methods for rate-modulating permanent pacemakers. AB - OBJECTIVES: The aim of this study was to develop a technique for quantitating chronotropic response. BACKGROUND: Although the importance of chronotropic response for optimizing cardiac output during exercise is widely recognized, methods for quantitating the rate-modulating behavior of permanent pacemakers have not been developed. For a method of quantitating chronotropic response to be clinically useful, the rate-modulating characteristics of a pacing system should be defined at the onset of exertion, over a variety of exercise work loads and during recovery. METHODS: Three methods for quantitation of rate modulation were assessed in 10 patients during treadmill exercise testing using the chronotropic assessment exercise protocol with expired gas exchange analysis. To compare the observed chronotropic response with a standard, the "expected" heart rate throughout exercise was calculated by using the concept of heart rate reserve as described by Wilkoff. The pacing rate observed during exercise was analyzed with 1) standard linear regression analysis, 2) comparison of observed and expected pacing rates at the midpoint and end of each quartile of exercise, and 3) integration of the area under the rate-response curve with comparison with the area under the expected curve. RESULTS: With use of a normalized scale relating change in heart rate to change in metabolic work load, with values of heart rate and metabolic work load at rest set to 0 and those at maximal exertion set to a value of 1, the mean y intercept for the study group was 0.10 +/- 0.20 (range 0.14 to +0.45), with a mean slope of 0.81 +/- 0.25 (range 0.31 to 1.19). The correlation coefficient relating change in heart rate to change in exercise work load was a mean of 0.90 +/- 0.09 (range 0.63 to 0.98). Integration of the area under the rate-response curve observed during exercise yielded a mean area that was 101 +/- 36% of that expected. When the range of exercise work loads was divided into quartiles, the area under the observed rate-response curve was 151 +/- 114% of that expected during the first quartile of exercise, 113 +/- 70% during the second, 96 +/- 38% during the third and 92 +/- 20% during the fourth. The mean area under the curve during recovery was 93 +/- 29% of that expected. Although calculation of the observed heart rate as a percent of that expected at the midpoint and end of each quartile of exercise used fewer observations, it provided similar results. CONCLUSIONS: Quantitation of the rate-response curve with comparison with the expected heart rate curve provides accurate methods for quantitation of chronotropic response. Adoption of this method would facilitate comparisons of artificial sensors and provide a framework to address issues of optimal rate modulation. PMID- 1452928 TI - Flosequinan, a new vasodilator: systemic and coronary hemodynamics and neuroendocrine effects in congestive heart failure. AB - OBJECTIVES: The aim of this study was to evaluate the immediate and long-term systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan in patients with congestive heart failure. BACKGROUND: Preliminary studies have shown that this new long-acting oral systemic vasodilator may have beneficial effects in patients with heart failure. METHODS: Thirteen patients with congestive heart failure were studied. Systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan were assessed acutely with repeat systemic hemodynamic studies after 6 weeks of treatment. RESULTS: The administration of flosequinan acutely and after long-term treatment, resulted in a significant increase in cardiac index, stroke work index and stroke volume index with a reduction in systemic and pulmonary vascular resistances. The improvement in ventricular function was associated with an improvement in left ventricular efficiency without a change in myocardial oxygen consumption or coronary sinus blood flow. Myocardial oxygen extraction and net myocardial lactate extraction also did not change significantly with flosequinan therapy. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma arterial and coronary sinus atrial natriuretic factor concentrations were elevated at baseline; the latter concentrations at the level of the great cardiac vein were significantly higher than those of arterial concentrations, indicating increased left ventricular release of atrial natriuretic factor in congestive heart failure. Both arterial and coronary sinus atrial natriuretic factor levels were significantly reduced with the administration of flosequinan at peak effect in association with an improvement in systemic hemodynamics. CONCLUSIONS: Flosequinan therapy in patients with congestive heart failure results in a sustained beneficial hemodynamic action and improved cardiac performance without an increase in metabolic demand or activation of the sympathetic nervous system. PMID- 1452929 TI - Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure. AB - OBJECTIVES: This study was undertaken to determine if a standard dose of aspirin interacts relevantly with the circulatory effects of enalapril in severe heart failure. BACKGROUND: The frequent association of heart failure with coronary artery disease confers potential for combined treatment with an angiotensin converting enzyme inhibitor and the prostaglandin synthesis inhibitor aspirin, the pharmacodynamic actions of which are, in part, mutually opposed. METHODS: In 18 patients, on 3 consecutive days, hemodynamic measurements were performed at baseline and 4 h after administration of a double placebo, enalapril (10 mg) plus placebo and enalapril plus aspirin (350 mg) according to a double-blind, randomized, crossover protocol. RESULTS: Enalapril given before aspirin led to significant decreases in systemic vascular resistance, left ventricular filling pressure and total pulmonary resistance together with a significant increase in cardiac output. When given with or on the day after aspirin, enalapril did not elicit significant changes in any of these variables. There was a clear tendency to lower values for pulmonary artery pressure on all regimens, and slowing of the heart rate was incurred whether or not aspirin had been given. Chi-square analysis of the individual responses showed that the probability of effecting a decrease in systemic vascular resistance > or = 300 dynes.s.cm-5 was six times greater when enalapril was given without aspirin (p < 0.01). CONCLUSIONS: In severe heart failure, the prostaglandin synthesis inhibition by aspirin counteracts the systemic arterial vasodilation of angiotensin-converting enzyme inhibition with enalapril and substantiates its dependence on the integrity of prostaglandin metabolism. Trends toward reductions of pulmonary artery pressure and slowing of the heart rate were still observed, presumably subsequent to lowered norepinephrine concentrations indicating maintenance of prostaglandin independent actions of angiotensin-converting enzyme inhibition. PMID- 1452930 TI - Amiodarone therapy does not compromise subsequent heart transplantation. AB - OBJECTIVES: The objective of this study was to determine the frequency of pulmonary complications, feasibility of early hospital discharge and requirements for postoperative inotropic and chronotropic support in patients receiving amiodarone therapy before heart transplantation. BACKGROUND: Although many patients waiting for heart transplantation will die of arrhythmias before a donor heart is found, the use of amiodarone has been limited by concern about increased complications in the perioperative period. METHODS: The 29 patients receiving amiodarone at the time of heart transplantation at University of California, Los Angeles Medical Center between October 1986 and September 1990 were compared with 29 control recipients to evaluate postoperative morbidity. Patients were receiving amiodarone for recurrent ventricular tachyarrhythmias (n = 11), atrial fibrillation (n = 2) or complex ventricular ectopic activity (n = 16). The average daily dose was 360 +/- 230 mg/day for an average of 11 +/- 22 months before transplantation. Amiodarone and control groups had a similar ejection fraction (0.18 +/- 0.07 vs. 0.20 +/- 0.08), frequency of coronary disease, age and gender. There were three more status I patients in the control group. OKT3 was given to only two patients receiving amiodarone and 12 control patients at high risk for renal dysfunction. RESULTS: Postoperatively, the duration of assisted ventilation was 21 +/- 19 h after amiodarone therapy versus 26 +/- 2 h in the control group (20 +/- 18 h vs. 15 +/- 9 h after excluding patients receiving OKT3), discharge arterial oxygen saturation was > 95% in both groups. Two patients in the amiodarone group with a smoking history of > 100 pack-years developed bilateral pulmonary infiltrates of brief duration. Although patients receiving amiodarone required atrial pacing more frequently (eight vs. two patients) and had a lower heart rate at discharge (75 +/- 18 vs. 86 +/- 11 beats/min), the duration of inotropic support (2.1 +/- 1.5 vs. 3.5 +/- 2.5 days) and of hospital stay (10 +/- 3 vs. 15 +/- 10 days) was not higher in the amiodarone than in the control group. The mortality rate at 30 days was similar in the two groups (6.8% vs. 3.4%, p = NS). CONCLUSIONS: Amiodarone therapy before heart transplantation may contribute to occasional pulmonary complications but does not significantly increase perioperative morbidity or mortality with the regimens used in this retrospective study. PMID- 1452931 TI - Comparative effects of diabetes mellitus and hypertension on physical properties of human large arteries. AB - OBJECTIVES: The effects of hypertension and diabetes on the physical properties of large arteries were compared in men. BACKGROUND: Although these two diseases are linked to vascular stiffening, no study has analyzed whether the arterial rigidity in diabetes is as substantial as in hypertension. METHODS: Noninvasive measurements of brachial artery mean pressure, diameter (pulsed Doppler study) and compliance (pulse wave velocity) were obtained in 29 men: 11 control subjects, 9 hypertensive nondiabetic patients and 9 diabetic normotensive patients. Individual diameter- and compliance-pressure curves extrapolated from the measured diameter and mean pressure point with a logarithmic elastic model permitted calculation of isobaric diameter and compliance at the same pressure in each subject. RESULTS: Compared with control subjects, hypertensive patients had a larger brachial artery measured diameter and isobaric diameter (p < 0.01) and lower measured and isobaric compliance (p < 0.001, p < 0.01). Compared with control subjects, diabetic patients had lower measured and isobaric compliance (p < 0.01). Comparison of diabetic and hypertensive patients showed that measured diameter and isobaric diameter were decreased in the former (p < 0.01). In the control and hypertensive groups, mean pressure correlated positively with measured diameter and isobaric diameter (p < 0.01) and negatively with measured and isobaric compliance (p < 0.001 and p < 0.01, respectively). In the control and diabetic groups, fasting glucose correlated negatively with measured and isobaric compliance (p < 0.01, p < 0.05). CONCLUSIONS: Intrinsic alterations of the large artery independent of a stretching pressure effect reduce arterial elasticity similarly in those with hypertension or diabetes. The loss of compliance is related to the chronic elevation of blood pressure in hypertension and to that of glycemia in diabetes and is associated with a relative large artery vasoconstriction in diabetic patients as compared with patients with hypertension. PMID- 1452932 TI - Pressure overload-induced cardiac hypertrophy with and without dilation. AB - OBJECTIVES: The present study was designed to produce a small animal model showing compensated hypertrophy followed by congestive heart failure within a reasonable time period. BACKGROUND: Although there are various large animal experimental models of hypertrophy and heart failure, the occurrence of these two stages within a reasonable time period has not been shown very successfully in small animals. METHODS: A mildly constricting band was placed around the ascending aorta of very young guinea pigs (mean age 25 +/- 3 days) to impose a gradually increasing pressure overload. The animals were examined at different postoperative intervals up to 20 weeks. RESULTS: At 10 weeks, there was a 56% increase in ventricular weight/body weight ratio, a 33% increase in left ventricular wall thickness and a significant increase in left ventricular systolic pressure. The animals with 20 weeks of banding had developed various clinical symptoms of congestive heart failure including dyspnea, cyanotic appearance of the extremities, hydrothorax and ascites. Although at this stage there was 86% hypertrophy, the increase in wall thickness was only 20%, indicating cardiac dilation. Depressed left ventricular systolic pressure and increased left ventricular end-diastolic pressure and the increase in wet weight/dry weight ratio in the lungs and liver at 20 weeks also indicated the occurrence of heart failure. The collagen content in the heart of animals with banding for 10 and 20 weeks was 160% and 240%, respectively, of that in corresponding sham control animals. CONCLUSIONS: The data suggest that the heart was in a stage of compensated hypertrophy for up to 10 weeks, whereas heart failure was seen at 20 weeks. The two functional stages, compensatory hypertrophy followed by prolonged failure, make this model appropriate for studies on the transition of heart hypertrophy to congestive heart failure. PMID- 1452933 TI - Pressure recovery in aortic stenosis: an in vitro study in a pulsatile flow model. AB - OBJECTIVES: This study was designed to study pressure recovery in various models of aortic valve stenosis by performing hemodynamic measurements under physiologic conditions in a pulsatile aortic flow circuit. The results were used to validate calculations of pressure recovery based on theoretic considerations derived from fluid dynamics. BACKGROUND: Pressure recovery in aortic stenosis has not been systematically analyzed. METHODS: Stenoses varying in size, shape (circular, Y shaped, slitlike) and inlet configuration (sharp-edged, nozzle-shaped inlet, artificially stenosed bioprostheses) were used. Aortic pressures were measured at multiple sites distal to the stenotic orifice to determine pressure gradients and recovery. RESULTS: With decreasing orifice area (2, 1.5, 1 and 0.5 cm2) pressure recovery increased (5, 7, 10 and 16 mm Hg, respectively) and the index pressure recovery to maximal peak to peak gradient decreased (56%, 37%, 24% and 14%, respectively). For a given orifice size of 0.5 cm2, this index ranged between 12% for a Y-shaped orifice and 15% for a circular orifice with a nozzle (cardiac output 4 liters/min). Increasing the cardiac output increased pressure recovery, whereas the ratio of pressure recovery to maximal pressure gradient remained constant. CONCLUSIONS: The index pressure recovery to transvalvular pressure gradient, which expresses the hemodynamic relevance of pressure recovery, decreases with increasing severity of aortic stenosis but is independent of transvalvular flow. Thus, pressure recovery is of minor importance in severe aortic stenosis but may account for discrepancies between Doppler and manometric gradients observed in patients with mild to moderate aortic stenosis or a prosthetic valve in the aortic position. PMID- 1452934 TI - Left ventricular shape is the primary determinant of functional mitral regurgitation in heart failure. AB - OBJECTIVES: The aim of this study was to examine the temporal association between the onset of functional mitral regurgitation and the development of changes in left ventricular shape, chamber enlargement, mitral anulus dilation and regional wall motion abnormalities during the course of evolving heart failure. BACKGROUND: Despite extensive characterization, the exact etiology of functional mitral regurgitation in patients with chronic heart failure remains unknown. METHODS: Heart failure was produced in seven dogs by multiple sequential intracoronary microembolizations. Serial changes in left ventricular chamber volume and shape were evaluated from ventriculograms. Changes in mitral anulus diameter and ventricular regional wall motion abnormalities were evaluated echocardiographically. The presence and severity of mitral regurgitation were determined with Doppler color flow mapping. Measurements were obtained at baseline and then biweekly until mitral regurgitation was first observed. RESULTS: No dog had mitral regurgitation at baseline but all developed mild to moderate regurgitation 12 +/- 1 weeks after the first embolization. The onset of mitral regurgitation was not associated with an increase in left ventricular end diastolic volume relative to baseline (58 +/- 3 vs. 62 +/- 3 ml), mitral anulus diameter (2.4 +/- 0.1 vs. 2.4 +/- 0.1 cm) or wall motion abnormalities of left ventricular wall segments overlying the papillary muscles. In contrast, the onset of mitral regurgitation was accompanied by significant changes in global left ventricular shape evidenced by increased end-systolic chamber sphericity index (0.22 +/- 0.02 vs. 0.30 +/- 0.01) (p < 0.01) and decreased end-systolic major axis/minor axis ratio (1.71 +/- 0.05 vs. 1.43 +/- 0.04) (p < 0.001). CONCLUSIONS: These data indicate that transformation of left ventricular shape (increased chamber sphericity) is the most likely substrate for the development of functional mitral regurgitation. PMID- 1452935 TI - Early and rapid prediction of patency of the infarct-related coronary artery by using left ventricular wall thickness as measured by two-dimensional echocardiography. AB - OBJECTIVES: The aim of this study was to determine whether echocardiography can distinguish between persistent coronary occlusion and reperfusion. BACKGROUND: There are no adequate clinical or noninvasive laboratory markers to accurately predict successful reperfusion in an acute myocardial infarction. METHODS: In a closed chest swine model, the effect of reperfusion on myocardial wall thickness was studied by comparing a 150-min total coronary artery occlusion (group 1) with 120 min of occlusion followed by 30 min of reperfusion (group 2) in the area of risk as measured by echocardiography. Wall thickness was measured at baseline and at 90 and 150 min. RESULTS: In group 1 (n = 4), there was no appreciable change in mean wall thickness from 90 min to 150 min of occlusion at either end-diastole or end-systole (0.54 +/- 0.02 to 0.52 +/- 0.03 cm, 0.55 +/- 0.03 to 0.54 +/- 0.03 cm, respectively; p = NS). In contrast, in group 2 (n = 6), an increase in mean wall thickness from 0.53 +/- 0.02 to 0.97 +/- 0.05 cm at end-diastole and from 0.56 +/- 0.04 to 1.04 +/- 0.07 cm at end-systole was found from 90 min of occlusion to 30 min of reperfusion (p < 0.001). Reperfusion resulted in an increase in wall thickness of 83 +/- 11% at end-diastole and 92 +/- 17% at end systole. In contrast, persistent coronary occlusion showed minimal changes of 3.0 +/- 5% at end-diastole and -2.0 +/- 6% at end-systole. CONCLUSIONS: This study confirms the hypothesis that an increase in wall thickness can accurately distinguish between reperfusion and permanent coronary occlusion. PMID- 1452936 TI - Comparison of single-photon emission computed tomographic (SPECT) myocardial perfusion imaging with thallium-201 and technetium-99m sestamibi in dogs. AB - OBJECTIVES: The purpose of the present study was to compare single-photon emission computed tomographic (SPECT) myocardial images of technetium-99m (Tc 99m) sestamibi and thallium-201 (Tl-201) isotopes in the same dog undergoing partial coronary occlusion during pharmacologic vasodilation. BACKGROUND: To date, no controlled study has been reported comparing SPECT Tc-99m sestamibi with SPECT Tl-201 imaging during stress with anatomic and physiologic standards. METHODS: Mongrel dogs were anesthetized with chloralose and instrumented to record left anterior descending coronary blood flow and aortic pressure. Partial coronary occlusion with a hydraulic cuff reduced coronary vascular conductance, which is equal to the coronary blood flow normalized to aortic pressure during peak vasodilation with intravenous adenosine. Each dog received 5 mCi of Tl-201, then 30 mCi of Tc-99m sestamibi during partial coronary occlusion at peak vasodilation. Tomographic myocardial imaging was performed in a 180 degrees anterior arc scan for 33.5 min, first with Tl-201, and later, without moving the dog, for 33.5 min with Tc-99m sestamibi. Postmortem staining defined the region underperfused because of its dependence on the artery that was partially occluded. RESULTS: In seven dogs with moderate reduction in coronary blood flow, coronary vascular conductance decreased with partial coronary occlusion (47 +/- 12%) during Tl-201 imaging and (47 +/- 8%, p = NS) during Tc-99m sestamibi imaging. The underperfused region was 23.9 +/- 6.4% of total left ventricular mass. Counts in the defects were 39% higher (0.86 +/- 0.08 of normal counts) for Tc-99m sestamibi than for Tl-201 (0.64 +/- 0.09 of normal counts, p < 0.001), and the defect on SPECT Tc-99m sestamibi images occupied only a fraction (0.37 +/- 0.30) of the area of the defect on the Tl-201 images of the same dog. Bull's-eye displays constructed from the pathologic slices showed that the Tl-201 defect size was closer to the underperfused region of the left ventricular mass determined pathologically than was the Tc-99m sestamibi defect size. In four additional dogs a severe, near total coronary occlusion was created during Tl-201 and Tc-99m sestamibi administration. In these dogs, similar defect contrast (0.55 +/- 0.12 vs. 0.62 +/- 0.09, p = NS) and areas (0.18 +/- 0.07 vs. 0.18 +/- 0.11, p = NS) were observed with Tl-201 and Tc-99m sestamibi, respectively. CONCLUSIONS: Tomographic myocardial imaging with Tc-99m sestamibi during moderately severe partial coronary occlusion underestimated the area of the defect relative to Tl 201 or to the pathologic reference standard in dogs. Defect contrast was sharper with tomographic myocardial Tl-201 than with tomographic myocardial Tc-99m sestamibi during moderately severe partial coronary occlusion. PMID- 1452937 TI - Marked systemic hypotension depresses coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator. AB - OBJECTIVES: This study was designed to test the hypothesis that the level of aortic blood pressure affects the rate and extent of coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator (rt-PA). BACKGROUND: Although many studies have confirmed the efficacy of thrombolytic therapy in the treatment of acute myocardial infarction, the effects of altered blood pressure on coronary thrombolysis have not been studied. Because the aortic pressure represents the coronary artery inflow pressure, first principles predict that changes in blood pressure will affect the delivery of the thrombolytic agent and thus affect thrombolysis. METHODS: The effects of large changes in blood pressure on coronary thrombolysis were studied in a canine model. Coronary thrombosis was induced by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, 24 dogs were classified into three groups of 8 dogs each: Group 1 dogs underwent phlebotomy to adjust systolic blood pressure to 130 mm Hg; Group 2 dogs underwent phlebotomy to decrease systolic blood pressure to 75 mm Hg. Dogs in Group 3 also underwent phlebotomy to achieve a systolic blood pressure of 75 mm Hg and then received norepinephrine to increase this pressure to 130 mm Hg. After adjustment in blood pressure, all dogs received an infusion of rt-PA (0.25 mg/kg body weight) over 30 min through the left anterior descending artery catheter. In a fourth group of six dogs, the effect of altered blood pressure on the rate of coronary thrombolysis was assessed. RESULTS: In dogs in Groups 1 and 3, the rate and extent of coronary thrombolysis were significantly increased compared with values in Group 2. In each of the six Group 4 dogs the rate of coronary thrombolysis increased when norepinephrine increased systolic blood pressure from 75 to 130 mm Hg. CONCLUSIONS: These results indicate that a moderate increase in coronary inflow pressure increases the rate and extent of coronary thrombolysis compared with values during marked systemic hypotension. PMID- 1452938 TI - Delineation of acute myocardial infarction with dysprosium DTPA-BMA: influence of dose of magnetic susceptibility contrast medium. AB - OBJECTIVES: The contrast enhancement of acutely infarcted myocardium produced by the nonionic magnetic susceptibility-enhancing agent dysprosium diethylenetriamine pentaacetic acid-bis-methylamide (DyDTPA-BMA [S-043 Injection]) was assessed in the current study to establish the lowest dose that would yield optimal contrast between normal and acutely infarcted myocardium. BACKGROUND: Magnetic susceptibility contrast agents enhance differences between normal and ischemic tissue by reducing the signal of the normally perfused tissue to which they distribute. METHODS: Acute myocardial infarctions were produced by ligation of the left coronary artery. At 3 to 4 h after occlusion, a dose of 0.1, 0.3 or 0.5 mmol/kg of DyDTPA-BMA was injected intravenously into eight rats each in group 1, 2 or 3, respectively; a fourth group of seven rats served as a control group. Nuclear magnetic resonance (NMR) transverse relaxation time (T2) weighted images (electrocardiographically gated to every 5th beat, echo delay time [TE] = 60 ms) were acquired before and for 1 h after administration of contrast agent. RESULTS: Images obtained before the injection of contrast agent showed moderate differences in signal intensity between normal and infarcted myocardium (p < 0.05). The contrast enhancement and the duration of delineation between infarcted and normal myocardium produced by this agent were dose dependent. At doses of 0.1, 0.3 and 0.5 mmol/kg, DyDTPA-BMA produced signal loss in normal myocardium: 63 +/- 5%, 41 +/- 4% and 28 +/- 4% of the baseline values, respectively, without any significant reduction in signal intensity of the infarcted region. The reduction in signal of normal myocardium and delineation of the infarct persisted for 5 min at a dose of 0.1 mmol/kg, for 20 min at a dose of 0.3 mmol/kg and for 40 min at a dose of 0.5 mmol/kg. No change in signal intensity or signal intensity ratio between normal and infarcted myocardium was observed in the control group during the same observation period. CONCLUSIONS: These results suggest that low doses of this agent, comparable to those of longitudinal relaxation time (T1)-enhancing agents, can delineate acutely infarcted myocardium. A dose of 0.3 mmol/kg of DyDTPA-BMA (S-043 Injection) provides reasonably persistent demarcation of acute myocardial infarction. Because this dose dramatically suppresses the NMR signal of normal myocardium, it shows the infarcted region as a region of high intensity (bright spot) on NMR images. PMID- 1452939 TI - Effect of Buckberg cardioplegia and peripheral cardiopulmonary bypass on infarct size in the closed chest dog. AB - OBJECTIVES: To simulate a human catheterization laboratory setting of controlled reperfusion during myocardial infarction, regional infusion of commercially available Buckberg cardioplegic solution and peripheral vented bypass were administered in the closed chest dog. BACKGROUND: Studies in open-chest dogs have demonstrated a significant reduction in infarct size and improvement in regional wall motion with a similar controlled reperfusion method using infusion of substrate-enriched (Buckberg) cardioplegic solution during cardiopulmonary bypass coupled with left ventricular venting. METHODS: After 100 or 180 min of balloon occlusion of the proximal left anterior descending artery, controlled reperfusion was performed with cardioplegic infusion and vented bypass. Dogs matched for occlusion time underwent balloon deflation without bypass or cardioplegia (uncontrolled reperfusion groups). Microspheres were used to quantify coronary ischemia during balloon inflation. All four groups (n = 8 to 9 per group) were followed up at 1 week to determine regional wall motion and infarct size. RESULTS: Qualitative echocardiographic analysis demonstrated no significant difference among groups in recovery of regional wall motion at 1 week; however, wall motion improved significantly in all groups between the ischemia and 1-week recovery periods. The histologic infarct size compared with the area at risk for dogs with uncontrolled versus controlled reperfusion, respectively, was 17.9 +/- 10.5% versus 31.9 +/- 8.3% (p < 0.05) for dogs with 100 min of occlusion and 40.1 +/- 11.7% versus 46.2 +/- 8.4% (p = NS) for dogs with 180 min of occlusion. A greater rate-pressure product in the dogs with controlled reperfusion after 100 min of occlusion (p < 0.05) may explain the larger infarct size observed for that group. CONCLUSIONS: These results demonstrate that regional infusion of substrate enriched cardioplegic solution in combination with peripheral vented bypass does not further reduce infarct size after prolonged ischemia in the closed chest dog (compared with uncontrolled reperfusion). PMID- 1452940 TI - Effect of chronic supraventricular tachycardia on left ventricular function and structure in newborn pigs. AB - OBJECTIVES: The purpose of this study was to examine the effects of supraventricular pacing tachycardia on left ventricular function and myocardial structure in newborn, immature pigs and to determine whether immature pigs respond to supraventricular tachycardia differently from adults. BACKGROUND: Previous studies have shown that supraventricular tachycardia causes dilated cardiomyopathy in adult animals; however, in humans, supraventricular tachycardia induced congestive heart failure occurs most frequently in children and newborns. Because some clinical diseases may cause myocardial failure in adults but rarely do so in children, it was hypothesized that the effects of supraventricular tachycardia in newborns may be different from those in adults. METHODS: In two groups of newborn swine (3 weeks of age), left ventricular volume, mass and function were assessed with simultaneous echocardiography and cardiac catheterization and myocardial structure was examined with light and electron microscopy. Six piglets underwent 3 weeks of left atrial pacing tachycardia (240 beats/min) and six littermates served as a control group. Both groups were followed up for 3 weeks. RESULTS: At the end of the protocol, left ventricular dimensions increased in the piglets with supraventricular tachycardia compared with values in the control group, but there were no differences in left ventricular mass. Systolic function, assessed by fractional shortening, peak ejection rate and maximal rate of pressure development, was decreased in the group with supraventricular tachycardia. The fractional shortening-end-systolic stress relation in the piglets with supraventricular tachycardia decreased below normal values. Left ventricular diastolic function assessed by the relaxation time constant was prolonged, the peak filling rate was decreased and left ventricular stiffness was increased in the supraventricular tachycardia group. The morphologic data demonstrated that supraventricular tachycardia did not change total myocyte volume but did decrease total myofibrillar volume. CONCLUSIONS: Supraventricular tachycardia caused dilated cardiomyopathy in immature pigs. These changes in left ventricular function were associated with a decrease in cellular contractile proteins. Thus, the effects of supraventricular tachycardia on left ventricular function and structure in immature animals were comparable to previous findings in mature animals. PMID- 1452941 TI - Echocardiographic "smoke" is produced by an interaction of erythrocytes and plasma proteins modulated by shear forces. AB - OBJECTIVES: This study was designed to determine the blood elements responsible for spontaneous echocardiographic contrast. BACKGROUND: Spontaneous contrast or "smoke" is an echocardiographic image usually found in low flow conditions. Two blood elements, erythrocytes and platelets, have been related to the generation of smoke. METHODS: The echogenicity of porcine blood products was assessed in static and flow conditions and was graded on a digitized videodensity computer program that assigned a score of 0 for black and 100 for white images. Blood elements were circulated from a small tube (4-mm diameter) into a larger cylindric chamber (30-mm diameter) under controlled flow rate conditions. The following blood products were studied: whole blood, platelet-depleted blood, platelet-rich plasma, platelet-poor plasma, erythrocytes suspended in saline solution, adenosine diphosphate (ADP) added to platelet-rich plasma, and saline solution as a control medium. RESULTS: As blood flow was increased in 30 ml/min increments from 0 to 180 ml/min, whole blood echo videodensity (scale 0 to 100) progressively decreased in the larger tube from 38 and 42 to 20, 12, 14, 16 and 14, respectively. When flow increased from 0 to 30 ml/min in the smaller tube, corresponding to a wall shear rate of 0 to 80 s-1, the blood entering the chamber was completely echolucent. The echogenicity of blood products in the larger tube was for static flow (0 ml/min) and high flow (180 ml/min), respectively: platelet depleted blood = 36 and 14; platelet-rich plasma = 2 and 2; platelet-poor plasma = 0 and 0; erythrocytes in saline solution = 8 and 12; ADP added to platelet-rich plasma = 0 and 15; saline solution = 0 and 0. Because platelets alone were nonechogenic but platelet-depleted blood produced a flow-dependent echogenicity similar to that produced by whole blood, platelets may not be involved in the production of smoke. However, when platelets were aggregated by ADP, they were echogenic but in dense clumps and in a flow-independent pattern not typical of the smokelike images. Erythrocytes suspended in saline solution had an intermediate density image. CONCLUSIONS: Echogenic smoke appears to be due primarily to the interaction of red blood cells and plasma proteins at low flow and low shear rate conditions. PMID- 1452942 TI - Mitral regurgitant jets after valvuloplasty--I. PMID- 1452943 TI - Mitral regurgitant jets after valvuloplasty-II. PMID- 1452944 TI - Meta-analyses of the effects of thrombolysis and aspirin on clinical outcomes. PMID- 1452945 TI - Choline: an important nutrient in brain development, liver function and carcinogenesis. AB - Choline is required to make certain phospholipids which are essential components of all membranes. It is a precursor for biosynthesis of the neurotransmitter acetylcholine and also is an important source of labile methyl groups. Much attention has been given to the effect of supplemental choline upon brain function, i.e., enhancement of acetylcholine synthesis and release. In addition, choline supplements administered to rats in utero or shortly after birth permanently after brain function. The mechanisms for this effect is unknown and under investigation at this time. Healthy humans fed diets deficient in choline, and humans fed parenterally have decreased plasma choline concentrations and develop liver dysfunction that is similar to that seen in choline-deficient animals. In experimental animals, fatty liver occurs in choline deficiency because phosphatidylcholine synthesis is required for very low-density lipoprotein secretion. This accumulation of lipids in liver may explain why choline-deficient rats spontaneously develop hepatocarcinoma. We found that choline deficiency was associated with the accumulation of 1,2-diacylglycerol, an activator of protein kinase C. Several lines of evidence indicate that cancers might develop secondary to abnormalities in protein kinase C-mediated signal transduction. PMID- 1452946 TI - Effect of interleukin-2 on some micronutrients during adoptive immunotherapy for various cancers. AB - In 20 patients, we investigated the effect of interleukin-2 (IL-2) treatment during adoptive immunotherapy for various cancers on circulating levels of: thiamin; biotin; folate; pantothenate; riboflavin; nicotinate; vitamins A, B6, B12 and E; carotenes; free and total cholines; inositol; and free and total carnitines. Of the above micronutrients, only vitamins A, B6, B12, inositol, carotenes and folate varied markedly from normal levels (pre IL-2 exposure) to abnormal levels (post IL-2). Following IL-2 exposure, every patient's B12 level was significantly elevated; 50% of the levels were abnormally increased above 1000 pg/ml. Extreme significant elevations of inositol were also seen in 90% of the patients. In contrast, IL-2 exposure depressed normal vitamins A, B6, carotene, and folate levels to subnormal; 90% of the patients became B6 hypovitaminemic; 60% for vitamin A, 80% for carotene, and 45% for folate. Other micronutrients tested showed no clear deviations from normal levels post IL-2 exposure. Some reasons for micronutrient variations are discussed. PMID- 1452947 TI - Vitamin E and cancer prevention: recent advances and future potentials. AB - Many animal and in vitro experiments have shown that the supplementation of diet with vitamin E within a certain dose range reduced the risk of chemical- and radiation-induced cancers. In vitro studies revealed that alpha-tocopheryl succinate (TS) induced differentiation and growth-inhibition in certain animal and human tumor cells in culture, whereas alpha-tocopherol (alpha-T), alpha tocopheryl acetate (alpha-TA) and alpha-tocopheryl nicotinate (alpha-TN) were ineffective, alpha-TS also reduced basal and ligand-stimulated adenylate cyclase activity, and expression of c-myc and H-ras oncogenes in certain tumor cells in culture. The relative efficacy of various forms of vitamin E in cancer prevention in animal or human models has not been evaluated. Human epidemiologic studies utilizing retrospective and prospective case-control experimental designs are not suitable for evaluating the role of vitamin E in cancer prevention due to several inherent problems associated with these methodologies. Intervention trials utilizing vitamin E with appropriate biological and statistical rationales are most suitable for testing the role of vitamin E in cancer prevention in humans. Some human trials utilizing vitamin E alone or in combination with other nutrients are in progress. PMID- 1452948 TI - Plasma amino acid responses of trained athletes to two successive exhaustion trials with and without interim carbohydrate feeding. AB - The purpose of this research was to measure changes in selected plasma amino acids (AA) during two successive exercise trials to exhaustion. Eleven trained male athletes completed these trials at weeks 4, 6, 8 and 12. Blood samples for each test were collected after a 12-hour fast at times (in minutes) 0 (Resting), 45, 90, 135, 180, at exhaustion (EI), after a 20-minute recovery period, and at the second exhaustion (EII). At the end of EI, subjects consumed an artificially sweetened water replacement (placebo) treatment or a carbohydrate (CHO) replacement (1.1 g CHO/kg BW) in order to determine any effect of CHO replacement on changes in energy substrates or AA, adjusted for plasma volume changes. From baseline to EI, alpha-aminobutyric acid, alanine, glycine, isoleucine, serine, valine threonine, and tyrosine decreased significantly (p less than or equal to 0.05), while taurine increased significantly. During the recovery period following EI, isoleucine, leucine, ornithine, phenylalanine, tyrosine, urea and valine increased significantly. From the end of recovery until EII, alanine, aspartic acid, glycine, isoleucine, leucine, ornithine, phenylalanine, serine, threonine, tyrosine and valine decreased significantly. CHO replacement had no effect on the mean change scores for any AA from EI to the end of the recovery period and affected only serine, citrulline, glycine and threonine from the end of the recovery period to EII. PMID- 1452949 TI - Role of nutrition in the management of malnutrition and immune dysfunction of trauma. AB - Current nutrition support improves patient outcome in trauma patients. It appears to do so by limiting the adverse effects of specific nutrient or generalized nutrient deficiencies. Immunosuppression, however, continues as a significant clinical problem. This immunosuppression appears to be part of the inflammatory response that accompanies trauma, and in part, to represent the need for conditional nutrients in this setting. Three nutrients that are being evaluated include arginine, uracil as ribonucleic acid and omega-3 polyunsaturated fatty acids. Animal studies report improved immune function. Early clinical trials are reporting improved immune function and patient outcomes. PMID- 1452950 TI - Benefits of oral protein supplementation in elderly patients with fracture of the proximal femur. AB - Malnutrition has been often suggested as contributing to both the high incidence of hip fracture in elderly people and its complications. In a recent prospective controlled randomized study, the clinical outcome of elderly patients with osteoporotic fracture of the proximal femur (hip fracture) improved by giving a simple oral dietary supplement. This study, however, did not prove that protein was responsible for the clinical improvement since the supplement also contained vitamins and minerals. We addressed this question by comparing the clinical outcome and bone mineral density (BMD) changes in elderly patients with hip fracture, receiving two different dietary supplements with different protein contents. Sixty-two patients (mean age 82) admitted into the orthopedic ward for fracture of the proximal femur were randomized into two groups. One group (n = 33) received 250 ml/day of an oral nutritional supplement containing protein (20.4 g), mineral salts (Ca: 0.525 g) and vitamins A = 750 IU; D3 = 25 IU) for a mean of 38 days. A control group (n = 29) received the same supplement dose, but with no protein, for the same period of time. The clinical course was significantly better in the group receiving protein, with 79% having a favorable course as compared to 36% (p less than 0.02) in the control group during the stay in the recovery hospital. The rate of complications and deaths was also significantly lower in the protein-supplemented vs the control group (52 vs 80%, p less than 0.05) 7 months after hip fracture. The median hospital stay was significantly lower in the protein-supplemented group (69 vs 102 days, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452951 TI - The Salt Step Test: its usage in the diagnosis of salt-sensitive hypertension and in the detection of the salt hypertension threshold. AB - The Salt Step Test was devised to characterize the response of the hypertensive patient to dietary salt. The test has three phases: unrestricted salt, to document hypertension and customary salt intake; restricted salt (2 g/day), to identify the salt-sensitive patient; and stepwise increased salt (each step = 1 g/day), to find the level that precipitates hypertension. The Salt Step Test identified that out of 30 well-established adult hypertensives, 13 were salt sensitive. It also revealed that in each salt-sensitive patient, a distinct level of salt (range 3-16 g/day) precipitated hypertension, i.e., a Salt Hypertension Threshold. Definition of the Salt Hypertension Threshold should be useful in providing specific, individualized guidelines for dietary salt restriction. PMID- 1452952 TI - Predicting total body water and extracellular fluid volumes from bioelectrical measurements of the human body. AB - Two biological impedance analyzers, a 50 kHz (RJL) and 20-100 kHz (BMA) instrument, and a total body electrical conductivity (TOBEC) instrument were used to estimate total body water (TBW), extracellular (ECF) and intracellular (ICF) fluid volumes by repeated measurements of 16 normal men (19-38 years old) to assess which, if any, would provide the best estimates. At 3-week intervals, TBW was determined by deuterium dilution, ECF by bromide dilution, ICF by difference (TBW-ECF) and lean body mass by density. Prediction equations were obtained by regression; predicted values for the body fluid volumes were calculated and the results were statistically evaluated. Both the TOBEC and the BMA provided rapid and reliable estimates for body fluid volumes with standard errors of the estimates of about 0.5-1.1 L for ECF, 1.0-1.8 L for TBW, and 1.0-1.3 L for ICF. Part of the error was attributable to standard tracer-dilution methods. PMID- 1452953 TI - Modification by food of the calcium absorbability and physicochemical effects of calcium citrate. AB - The food-calcium (Ca) interaction was examined in 12 healthy women (mean age 38 years) maintained on a constant metabolic diet. They underwent three phases of study, comprised of control (no Ca), Ca citrate (1 g Ca/day) during meals, and Ca citrate separately from meals. Each phase was 7 days in length and two 24-hour urine samples were collected on days 6 and 7. The rise from the control phase in urinary Ca was slightly more prominent when Ca citrate was given with meals than without (68 and 62%, respectively). The fall in urinary phosphorus was equivalent at about 25% between Ca citrate phases. The rise in urinary citrate and pH and the decline in urinary ammonium were more prominent when Ca citrate was given with meals; however, the changes were small or nonsignificant. The urinary saturation of Ca oxalate, brushite or monosodium urate did not differ between the two Ca citrate phases. There was a nonsignificant rise in serum iron during Ca citrate phases. The results suggest that: 1) dissolution and absorption of Ca citrate might be slightly greater when given with food than without; 2) that the ability of Ca citrate to attenuate crystallization of stone-forming Ca salts in urine is not modified by food; and 3) that Ca citrate may not impair iron absorption from food. PMID- 1452954 TI - Comparison of in vitro and in vivo tests for determination of availability of calcium from calcium carbonate tablets. AB - In vitro tests of calcium (Ca) availability and the oral Ca load test were conducted on eight brands of calcium carbonate (CaCO3) tablets (products A-H) each providing 500 mg Ca. Data were collected over three experiments with nine to 11 healthy premenopausal women testing two to four products. Subjects followed a low Ca diet (less than 10 mmol/day). On test mornings, fasting subjects collected baseline urine for 2 hours (-2 to 0 hours), then ingested the tablet with water. Urine was collected from 0 to 2 hours and 2 to 4 hours; for products E-H, urine was collected for an additional 2 hours (4 to 6 hours). Blood was sampled at hours 0, 4 and 6 during testing of products E and F. Three in vitro tests were run: the United States Pharmacopeia (USP) dissolution test, USP disintegration test, and a disintegration test using vinegar. Ca excretion rose significantly at hours 2 to 4 (p less than 0.05) compared to baseline for seven products. Ca excretion either fell or remained constant between hours 4 and 6. Serum Ca rose and serum parathyroid hormone fell at hour 4, compared to fasting values, suggesting that 4 hours represents peak response time. In vivo availability, measured as the incremental increase in Ca excretion (mmol/mmol creatinine) in hours 2 to 4 compared to baseline, did not correlate significantly with results of the USP dissolution test but did with results of either the USP disintegration test or the vinegar test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452955 TI - Further studies of the effect of zinc on intestinal absorption of calcium in man. AB - In a previous study dietary supplementation with 140 mg zinc (Zn) as Zn sulfate (ZnSO4) per day significantly decreased absorption of calcium (Ca) during a low Ca intake (230 mg/day) but not during a normal Ca intake (800 mg/day). The purpose of the present study was to determine whether smaller doses of Zn would also inhibit Ca absorption during the 230 mg Ca intake, and whether the 140 mg dose of Zn would inhibit Ca absorption during a Ca intake less than 800 mg/day. To investigate the first aspect, 100 mg Zn as ZnSO4, was given daily during a low Ca intake (230 mg/day) in six studies, and in the second phase, 140 mg Zn as ZnSO4 was given during a Ca intake of of 500 mg/day in five studies. Intestinal absorption of Ca was determined with tracer doses of 47CaCl2 in control studies and in the two Zn supplementation studies. Results showed that 100 mg Zn/day during a low Ca intake (230 mg/day) did not inhibit Ca absorption and that 140 mg Zn given during the 500 mg Ca intake also did not affect the absorption of Ca. PMID- 1452956 TI - Hypothesis: etiology of atherosclerosis and osteoporosis: are imbalances in the calciferol endocrine system implicated? AB - Atherosclerosis and osteoporosis are currently considered unrelated diseases. Osteoporosis involves bone calcium (Ca) loss and predominantly affects females after menopause. Atherosclerosis is an illness predominantly affecting males, and is primarily characterized by abnormal lipid metabolism. However, pathological calcification of the arterial wall is an underlying feature of atherosclerosis. Ca homeostasis is thus important in atherosclerosis as well as in osteoporosis. Men also develop osteoporosis although at a later age than women, and, as osteoporosis progresses in women, there is an accompanying calcification of arteries leading to increased incidence of atherosclerosis in aging women. Thus, during old age, both atherosclerosis and osteoporosis are prevalent in both males and females. The dramatic increase in atherosclerosis among women as they develop osteoporosis suggests that the two illnesses may be more closely related than previously realized. The use of vitamin D as a food supplement coincides with epidemic onsets of atherosclerosis and osteoporosis, and excess vitamin D induces both conditions in humans and laboratory animals. These observations suggest a role for chronic vitamin D excess in the etiology of the two illnesses. Magnesium (Mg) deficiency, nicotine, and high dietary cholesterol are contributing factors that accentuate adverse effects of vitamin D. PMID- 1452957 TI - Safeguarding supplements. US Pharmacopeia sets quality standards for FDA and the supplement industry. PMID- 1452958 TI - Food intake measurements: is there a "gold standard"? PMID- 1452959 TI - Improving dietitians' teaching skills. AB - Many health professionals lack important teaching skills, perhaps adding to patient difficulties in understanding and adopting therapeutic diets. Research suggests that teaching skills improved after dietitians took a continuing education course entitled "Effective Patient Teaching." Our study tested whether dietitians' new skills would persist in the field and whether selected patient outcomes would differ as a result. Thirty staff dietitians from six urban hospitals were videotaped teaching patients, then randomly assigned to take the Effective Patient Teaching course or not (control group). Follow-up videotapes were made after 1 week, 1 month, and 3 months. After each teaching session, patient satisfaction and recall were assessed. Two judges rated 20 teaching skills, which were divided into four subsets for analysis. Repeated measures analyses of variance showed overall gains only for the group that took the Effective Patient Teaching course, which scored higher than the control group at 1 week and 1 month, but not at baseline or 3 months. Gains occurred in presentation skills and essential teaching functions. Throughout the study, interpersonal skills were high and adherence promotion skills were low for dietitians in both groups. Groups did not differ on patient satisfaction or recall. Improvements in dietitians' teaching skills translated to the field immediately after they completed the continuing education program, but not all gains were sustained after 3 months. We recommend that dietitians assess their teaching and adherence promotion skills, obtain training where warranted, and periodically reassess the application of those skills during patient teaching sessions. PMID- 1452960 TI - Cravings and aversions of pregnant adolescents. AB - Adolescents from 31 eastern Tennessee counties were interviewed during the third trimester of pregnancy (n = 97) and at 1-year postpartum (n = 64) to assess cravings and aversions, beliefs about dietary cravings, and how these factors influence dietary intake. Characteristics of cravings and aversions were assessed using a semistructured interview. Beliefs about cravings during pregnancy were measured with a 13-item Likert-type scale (alpha = 0.79). Two 24-hour recalls and 2 days' food records provided dietary data. Most adolescents (86%) reported cravings during pregnancy. They most frequently reported cravings for sweets, especially chocolate; fruits and fruit juices; fast foods; pickles; ice cream; and pizza. Many participants (66%) experienced aversions during pregnancy toward previously liked foods. The most common aversions were to meats, eggs, and pizza. Fewer cravings and aversions were noted during the first year postpartum. No significant relationship existed between craving and aversions and belief scores. Adolescents craving sweets during pregnancy consumed more sugar and energy than those who did not crave sweets. Cravings generally resulted in increased intake, and aversions led to decreased food consumption. On the basis of these results, we suggest that nutritional assessment of pregnant adolescents include questions about cravings and aversions. PMID- 1452961 TI - Self-reported and measured weights and heights of participants in community-based weight loss programs. AB - Self-reported weights and heights of 82 adults were compared with measured weights and heights 1 to 3 years after participation in community weight loss programs. The mean self-reported weight was 2.3 +/- 1.9 kg lower than measured weight (P < .05). Differences in underreporting were not significant for gender or age group. Heavier individuals misreported their weight to a greater extent (P < .05) than lighter persons, and individuals who had not recently weighed themselves underreported their weight to a greater extent than those who had weighed recently (P < .05). On the average, height was overreported by a mean of 1.8 +/- 2.7 cm. Overreporting increased with increasing height, and men overestimated their height to a greater extent than women (P < .05). Younger subjects reported their height more accurately than those older than 60 years. Results of our study are similar to those of previous investigations that examined self-reporting bias in subjects enrolled in weight loss programs. The mean discrepancy in body weight, however, was greater than that reported in samples drawn from the general population. Our findings indicate that self reported weight and height values in overweight populations should be interpreted with caution. PMID- 1452962 TI - Dietary patterns of elderly Boston-area residents defined by cluster analysis. AB - The dietary patterns of 680 noninstitutionalized, predominantly white, elderly volunteers from the Boston area (447 women and 233 men) were examined by cluster analysis of food contribution to energy intake. Data were derived from 3-day dietary records. The four major patterns identified corresponded to high consumption of (a) alcohol, (b) milk, cereals, and fruits, (c) bread and poultry, and (d) meat and potatoes. The resulting clusters of subjects differed significantly in gender, education, income, and frequency of smoking. Those with diets high in milk, cereals, and fruits had the highest intakes of micronutrients and the best hematologic profile. Those with high meat and potato intakes had the lowest intakes of micronutrients and lowest levels of plasma folate and vitamin B 6. High alcohol consumers had lowest blood levels of riboflavin and vitamin B-12 and highest levels of high-density-lipoprotein cholesterol. Those with high bread and poultry intakes had lowest reported energy intakes, but, paradoxically, they had the highest mean body mass index. Neither total serum cholesterol nor cholesterol intake varied significantly among groups. Our findings suggest that the nutritional status of the elderly may be improved by promoting food patterns rich in milk, fruit, and cereals and by counseling the elderly to limit consumption of alcohol and meats high in saturated fats. PMID- 1452963 TI - Nutrient intakes of 2- to 10-year-old American children: 10-year trends. AB - Nutrient intakes of American children aged 2 to 10 years were compared for the years 1978 and 1988 using a unique nutrient assessment system designed and developed by the Nutrition Department at General Mills. This system integrated data from three sources: 14-day food consumption diaries collected from 4,000 households in the Market Research Corporation of America Menu Census panel surveys; serving-size data from the spring 1977 Nationwide Food Consumption Survey; and nutrient data from the Michigan State University Nutrient Data Bank. The results indicate that energy and macronutrient intakes remained fairly constant over the 10-year period. Average daily vitamin and mineral intakes were lower in 1988 than in 1978 for the majority of those studied; however, most nutrient levels remained over 100% of the Recommended Dietary Allowances (RDAs). For more than 50% of the population, the intakes of calcium, vitamin B-6, and zinc were below the RDAs. Our findings indicate the need for continued monitoring of the impact of changing food consumption patterns on the diets of American children. PMID- 1452965 TI - Journal reading habits of dietitians. AB - Professional journals are an important resource for continuing education. To explore the journal reading habits of registered dietitians (RDs), we mailed a questionnaire to all RDs in the state of Delaware. Responses were received from 71 RDs (47%) who identified 44 professional journals they rely on for current, practical information. RDs who have journals available at work tend to devote more time to reading at work than at home. The Journal of The American Dietetic Association was clearly the professional journal read with most regularity by respondents. Articles of practical interest, followed by abstracts and book reviews, were sections most widely read. Lack of time was the primary reason RDs identified for not devoting adequate time to reading. Many attempted to resolve this problem through reliance on newsletters and less involvement with journal articles. Suggestions for improving and maximizing journal reading habits are offered. PMID- 1452964 TI - Effects of dietary calcium from dairy products on ambulatory blood pressure in hypertensive men. AB - The effect of consumption of 400 mg vs 1,500 mg of dietary calcium per day was examined in 13 male volunteers who had been diagnosed as hypertensive. Dietary calcium consumption was varied by manipulation of the intake of dairy products over 4-week periods. Caffeine intake (mean = 500 mg/day) was monitored. Neither laboratory blood pressure measured by standard sphygmomanometry nor ambulatory blood pressure monitored by automated sphygmomanometry varied significantly among men consuming baseline, low-calcium, or high-calcium diets (laboratory blood pressure = 136/83, 133/83, and 137/84 mm Hg, respectively; ambulatory blood pressure = 136/86, 138/87, and 138/87 mm Hg, respectively). Serum ionized calcium values did not vary with the three diets (1.25, 1.26, and 1.25 mmol/L, respectively). The parathyroid hormone level decreased (39 mmol/L vs 37 mmol/L) and the urinary calcium:creatinine ratio was elevated (0.41 vs 0.50) in the high calcium diet. Consumption of a diet containing 1,500 mg calcium per day over 4 weeks did not produce a significant decrease in blood pressure or alterations in calcium metabolic indexes. PMID- 1452966 TI - Potential role of energy and nutrient intakes in decreasing the incidence of genitourinary tract infections in pregnant adolescents. PMID- 1452967 TI - Prepregnancy weight and rate of maternal weight gain in adolescents and young adults. PMID- 1452968 TI - A food frequency questionnaire that rapidly and accurately assesses intake of fat, saturated fat, cholesterol, and energy. PMID- 1452970 TI - Professional attitudes of dietetics students and practitioners. AB - The purpose of this study was to develop and validate an instrument for measuring differences in professional attitudes of dietetics students and practitioners. Comparisons were made between junior and senior dietetics students, new and experienced (5 years or more) registered members of The American Dietetic Association (ADA), and registered ADA members and registered nonmembers (individuals who dropped ADA membership). The sample consisted of 371 junior and senior students from 18 coordinated dietetics programs and 1,041 dietetics practitioners. Principal component analysis was used to categorize conceptually 51 professionalism statements into 13 factors identified as professional attitude scales. Mean scores for the two scales "personal obligations for professional development" and "mastery of substantive content" were highest for all three groups; lowest scores were for the scale "professional isolation." Overall, significant differences were found on eight scales for one or more of the comparison groups. Students rated the scale "respect for the profession's intellectual challenge" higher than did new and experienced registered ADA members. Discriminant analysis indicated that junior (70%) and senior students (65%) were successfully differentiated on four scales, new (62%) and experienced (60%) registered ADA members on five scales, and ADA members (70%) and nonmembers (72%) on four scales. Results of this study could be used by educators to support inclusion of concepts of professionalism in dietetics curriculums. Results also could aid practitioners in marketing their knowledge and skills by presenting a more positive professional image to clients. PMID- 1452969 TI - Food beliefs and diets of pregnant Korean-American women. PMID- 1452971 TI - The effects of probenecid on the excretion kinetics of stanozolol, an anabolic steroid, in rats. AB - The pharmacokinetic behaviour and the mechanism of renal excretion of stanozolol (STZ), as affected by co-treatment with probenecid, were studied in male Sprague Dawley rats. Pharmacokinetic parameters following intravenous (i.v.) administration of STZ (20 mg kg-1 body wt.) were measured in both STZ-treated (control) and STZ plus probenecid-treated (treatment) groups. In order to assess the renal clearance of STZ, bolus doses of STZ and inulin (40 mg kg-1 body wt.) were injected i.v. either in the presence or absence of probenecid (40 mg kg-1 body wt.). The blood and urine concentrations of STZ were determined by capillary gas chromatography-mass spectrometry (GC-MS). In the probenecid treatment group, the area under the plasma disappearance and urinary excretion curves (AUC) of STZ were significantly decreased (P < 0.01) and the volume of distribution (Vd) and total clearance (CLt) were significantly increased statistically (P < 0.05 and P < 0.01, respectively). No remarkable differences in the urine flow rate, urine pH values, glomerular filtration rate (GFR) or renal clearance were observed in the treatment group. However, the clearance ratio in the treatment group was significantly increased from 11.72 to 17.27. From these results, it is suggested that the significant decrease of AUC, i.e. increase of disappearance of STZ in plasma by co-administration with probenecid, is due to the increase of the clearance ratio. PMID- 1452972 TI - Retention of inhaled perfluoroisobutene in the rat. AB - Perfluoroisobutene (PFIB) is produced by the pyrolysis, and as a by-product during the manufacture, of polytetrafluoroethylene. When inhaled it produces a fulminating and sometimes fatal pulmonary oedema similar to that of phosgene after a latent period of 6-8 h. As part of a study to determine the retained dose and the factors that control the amount retained, this study has investigated the retention in rats of inhaled PFIB at concentrations of 10, 50 and 250 micrograms l-1 in a flow-through system combining head-only exposure and plethysmography. Uptake of PFIB was measured by gas chromatography during elevated and reduced inspired volume and respiratory rate induced by exposure to increased CO2 and injection of pentobarbitone, respectively. The percentage of PFIB retained in the upper airways and lungs was found to be 27.5, 28.1 and 23.7% of the amount inspired at the three concentrations tested. The rate of uptake (nmol min-1 kg-1) of PFIB was a power law of the amount inhaled, an n-fold increase in minute volume producing an nb-fold increase in uptake, where b varied between 0.4 and 0.85. Thus, doubling the inhaled dose produces a 1.3-1.8-fold increase in uptake with a corresponding decrease in percentage retained. The relative contribution of respiratory rate and tidal volume upon PFIB retention could not be defined. PMID- 1452973 TI - Effect of lead on hepatic microsomal enzyme activity. PMID- 1452974 TI - Magnetic resonance imaging of the rat brain following acute carbon monoxide poisoning. AB - Magnetic resonance (MR) may be used for repeatedly and non-invasively imaging the brain. Until now, no studies have used this approach to study the effects of carbon monoxide (CO) poisoning in a defined animal model. Conscious, Levine prepared female rats (unilateral carotid artery and jugular vein occlusion) were exposed to 2400 ppm CO for 90 min, with or without the infusion of 50% glucose solution; CO-stimulated increases in blood glucose and lactate occurred in both groups, while blood pressure and body temperature fell. One to four hours following termination of CO exposure, increased cortical pixel intensity, cortical surface area and brain midline shift were observed on the operated side of the brain in some rats of both groups (i.e. responders = R), providing evidence of edema. At sacrifice, 5 h following termination of CO exposure, gross water content was increased on the left side in the corresponding cortical slices in R rats, providing another measure of edema. Significant positive correlations were found between left to right pixel intensity difference and water content difference, and between the extent of midline shift and water content difference. The elevations of blood glucose and lactate concentrations, and the magnitudes of CO-induced hypothermia and hypotension were similar to those in past studies, but appeared to exert no effect on the severity of cortical edema in terms of differences in pixel intensity, surface area, midline shift or gross tissue water content. Thus, the observed differences between the R rats is not explained by the available data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452975 TI - Effects of 3-methylcholanthrene or diethyl maleate on the hepatotoxicity of acetaminophen. AB - This report presents a set of investigations on the hepatotoxic action of acetaminophen (AA). Male mice of Balb C strain were given [3H]acetaminophen in doses of 100, 300 and 600 mg kg-1 with or without pretreatment with 3 methylcholanthrene (3MCh) or diethyl maleate (DEM). The results of this study show that AA administered in moderate doses brings about necrotic changes due to adduct formation with macromolecules. Adduct formation was inversely correlated with the level of glutathione. Both modifiers enhanced hepatic necrosis and lethality. Diethyl maleate exerted these effects without enhancing covalent binding to macromolecules, while 3MCh increased both adduct formation and lipid peroxidation. PMID- 1452976 TI - Pulmonary reactivity to vanadium pentoxide following subchronic inhalation exposure in a non-human primate animal model. AB - An experimental study was conducted to evaluate changes in pulmonary reactivity resulting from repeated vanadium pentoxide (V2O5) dust inhalation. The study assessed pulmonary reactivity to V2O5 through the use of provocation challenges, and compared V2O5 reactivity before and after subchronic V2O5 exposure. A total of 24 adult, male cynomolgus monkeys (Macaca fascicularis) were exposed by inhalation for 6 h per day, 5 days per week, for 26 weeks. Two V2O5-exposed groups (n = 8 each) received equal weekly V2O5 exposures (concentration x time) with different exposure profiles. One V2O5-exposed group received 0.1 mg V2O5 m-3 on Mondays, Wednesday and Fridays, with a twice-weekly peak exposure of 1.1 mg V2O5 m-3 on Tuesdays and Thursdays, and was included to investigate the influence of an exposure regimen with peaks on the development of pulmonary hyper reactivity. The other V2O5-exposed group received a constant daily concentration of 0.5 mg V2O5 m-3. A control group (n = 8) received filtered, conditioned air. Pre-exposure challenges with V2O5 produced a concentration-dependent impairment in pulmonary function, characterized by airway obstructive changes (increased resistance and decreased flow). Analysis of respiratory cells recovered from the lung by bronchoalveolar lavage demonstrated that airway obstruction was accompanied by a significant influx of inflammatory cells into the lung. Subchronic V2O5 inhalation did not produce an increase in V2O5 reactivity in comparison to the control group, and cytological, immunological and skin test results indicate the absence of allergic sensitization. Instead, a trend toward decreased pulmonary reactivity was found following subchronic V2O5 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1452977 TI - The pattern of poisoning in urban Zimbabwe. AB - A 10-year (1980 to 1989 inclusively) retrospective analysis of poisoning admissions to the six major referral hospitals in Zimbabwe revealed 6018 cases. The majority of the patients were aged 0-5 years (35%) and 21-30 years (22.6%). The main agents associated with acute poisoning were traditional medicines (22.9% of the total), household chemicals (18.8%, 13.2% of which was due to paraffin), snake and insect envenomation (17.1%), orthodox medicines (16.7%) and insecticides (14.8%, 10% of which is accounted for by organophosphates). Mortality was 15% and the main agents associated with fatality were pesticides, traditional medicines and orthodox medicines, in descending order. The prevention and treatment of intoxication caused by traditional and orthodox medicines, the proper storage and disposal of pesticides and legislation regulating their sale and distribution are of high priority in the fight to reduce poisoning caused by these agents. PMID- 1452978 TI - User's review of the Canon Colour Copier. AB - The ability to link the new Canon Colour Laser Copier to a computer opens up new boundaries of data manipulation. A report from the user's point of view, describes a system comprising the copier with computer input, slide scanner and flat copy capacity. Information is given on the types of materials produced, the types of users, the cost of purchase and maintenance, and the potential for generating profit. PMID- 1452979 TI - Medical illustration enters the market economy. AB - The department of medical illustration at the Royal Postgraduate Medical School (RPMS) has been operating as a registered company for just over 1 year. As other similar departments are forced into cost recovery, some may be considering this extra step. This paper sets out some of the pitfalls as well as giving some handy tips which will make the journey down this uneven road a little easier. PMID- 1452980 TI - Endoscopy and endoscopic photography in ENT. AB - Doctors have been concerned with ear, nose and throat (ENT) diseases since the earliest times, but there was no single specialty before the introduction of endoscopic methods last century. Effective visualization of the ears, nose and throat poses significant problems for the medical illustrator today. The development of endoscopy and endoscopic photography is outlined with background information to help the illustrator who has to work in this field. PMID- 1452981 TI - Diabetic retinopathy screening service. AB - The planning, establishment, financing and general organization of a Diabetic Screening Service within a District Health Authority can be a daunting task if not handled correctly. This paper outlines such a service, established in 1987, at a District General Hospital serving a population of 202,000 permanent residents. It highlights the necessity for such a service and its diagnostic value to the local diabetic population. PMID- 1452982 TI - The Sri Lanka cleft lip and palate project--the medical illustrator's contribution. AB - Since 1984, a series of visits to the island of Sri Lanka by an assessment team, and a team of surgeons and anaesthetists, has amassed a huge dataset on unoperated cleft lip and palates and carried out surgery on over 600 patients. In addition, the training of local Sri Lankan professionals was undertaken. The two most recent trips in 1990 are described with reference to the photographic and audiovisual records collected. PMID- 1452983 TI - Ni-Cds: the memory lingers on. AB - The medical photographer's source of power for portable electronic flash has evolved from the disposable, single-use battery via the wet cell to the nickel cadmium rechargeable battery, and recently to the 'dry-fit' rechargeable battery. This paper looks at the ubiquitous nickel-cadmium rechargeable battery with reference to its charge/discharge cycling and chemical 'memory' during discharge, and compares single-use and other rechargeable batteries with respect to ease of use, capacity and working life. PMID- 1452984 TI - The image database: pictures and computers. AB - Information technology offers important new ways of using pictures for teaching in medicine. Methods for storing and delivering high quality images for computer based learning systems are discussed. PMID- 1452985 TI - The Wellcome Trust tropical diseases videodisc project. AB - This presentation sets out the aims and methodology involved in creating a sophisticated teaching archive in tropical medicine based on the Wellcome Museum of Medical Science. This visual archive will take the form of a videodisc database containing 30,000 video stills combined with a limited amount of moving material. While authoring tools will ensure the continuing production of interactive learning material from the archive, users will have access to several hundred hours of ready made tutorials, and an expert system to teach clinical skills. They will also be able to browse through any part of the archive. Successful management strategies have involved a close and supportive relationship with the project sponsors, the formation of expert groups to solve specific problems, and a process of continuous formative evaluation. PMID- 1452986 TI - A survey of videodisc and interactive videodisc projects in North America: Part I. AB - Selected videodisc (VD) and interactive videodisc (IVD) programs, projects and topics are presented in two articles in this and a subsequent issue of the journal. Part I reviews the impact of Information Science developments on image management. The American Society of Hematology Slide Bank and other specific applications in urology, paediatric neurology, obstetrical nursing, medical decision making, dental diagnosis and treatment (DDT), and paediatric cardiology, are reviewed as educational and informatics research projects. This is followed by a section on three-dimensional reconstructions of the brain which stresses digital images. Multi-purposing and repurposing are reviewed in two prototype programs. A discussion of the multidisciplinary Slice of Life projects completes this first article. PMID- 1452987 TI - An interactive videodisc 'cancer patients and their families at home', designed for education in primary health care. AB - This article describes the development of an interactive videodisc program to support professional education in the field of cancer for the primary health care team. Based on a survey of needs, it concentrates on common symptoms and their control, and problems in communication. The educational approach adopted was chosen on the basis of an extensive consideration of the needs, and what was felt most appropriate for adult learners. Plans were carefully reviewed at each stage, with external advisers, and the prototype system independently evaluated in four sites before completing the package. With financial backing from the 'Europe against Cancer' initiative of the European Commission, and close cooperation with national practitioners, Dutch, German, Greek and Portuguese versions of the package have been developed. Local differences in practice are taken into account and translations of key aspects are provided. PMID- 1452988 TI - Hypermedia in biomedical education: a case study. AB - The origination, development and application of a hypermedia system for use in the life sciences is described. Implemented in the Apple Macintosh HyperCard environment, the project has been designed to make use of commercially produced laser discs as visual archives and has included the production of authoring and navigational tools. We report here on our experience in authoring stacks for undergraduate teaching, monitoring of student use and assessment of effectiveness as a self-teaching resource. Future developments and applications within the biomedical sciences are discussed. PMID- 1452989 TI - Digital imaging--dipping a toe in the water. PMID- 1452990 TI - Redial generations of Fasciola gigantica in the pulmonate snail Lymnaea truncatula. AB - Lymnaea truncatula, 4 mm in height, were subjected to infection by a single miracidium of Fasciola gigantica, then raised at 23 degrees C until day 60 of the experiment. Histological study of these snails demonstrated a mean redial burden of 34 parasites at day 60, of which one third were degenerating forms. The mean number of living independent rediae did not exceed 5 for the first and second generations. Conversely, in subsequent generations there were as many as 18 rediae per snail at day 60. The first living redia of the first generation in particular gave rise to daughter rediae. Mature rediae appeared at day 35 and especially concerned the first and second generations at day 60. The authors conclude that development of the first and second redial generations occurs during the same period, and that the forms of the first cohort of the second generation are produced from the first redia of the first generation which originated from the sporocyst. PMID- 1452991 TI - Ultrastructural observations on the redial tegument of Paramphistomum epiclitum from the planorbid snail, Indoplanorbis exustus. AB - The morphology of the tegument in the redia of Paramphistomum epiclitum (Digenea: Paramphistomidae) resembles that shown by most larval and adult digeneans; an outer surface syncytium is in continuity with the cytoplasm of in-sunken, nucleated cytons. Although tegumental cytons usually contain a single nucleus, some display up to six nuclei. The tegumental syncytium lining the pharynx of P. epiclitum rediae lack underlying cytons. The apical membrane of the tegument is elaborated by folds and microvilli, which presumably facilitate uptake of nutrients and/or exchange of ions involved in osmoregulation. A single type of secretory body, resulting from the fusion of smaller vesicles produced at Golgi complexes in the cytons, occurs throughout the tegument. Uniciliate sensory receptors occur in the surface syncytium particularly around the oral opening. PMID- 1452992 TI - The diagnostic value of haematuria and proteinuria in Schistosoma haematobium infection in southern Nigeria. AB - Haematuria and proteinuria as detected by chemical reagent strips correlated moderately (r = 0.7) with prevalence and intensity of infection with Schistosoma haematobium in an area of Anambra State, Nigeria. Differences attributable to age and sex were also reflected in a similar pattern, all peaks occurring in the 5-14 year age group. The differences observed with varying levels of intensity and haematuria at both 10 and 50 erythrocytes/microliter (p < 0.001) and proteinuria at 0.3 g/dl (p < 0.01) were statistically significant. At a proteinuria level of 1 g/dl, the observed differences were however not statistically significant (p > 0.5). The percentage of specimens from children (0-14 years) positive for S. haematobium eggs and with at least traces of haematuria and proteinuria (63.4% and 95%, respectively) was higher than in adults (33.3% and 80.2%, respectively). All individuals with more than 50 eggs/10 ml of urine were correctly identified using both indices either separately or in combination. For egg counts of less than 50 eggs/10 ml of urine, false diagnosis occurred in only 5% of all specimens examined. The sensitivity and specificity of haematuria and proteinuria at trace quantities was very high, but haematuria had a higher predictive value for a positive test (PvPt) and was considered the overall better indicator. A combination of both indices did not significantly increase the PvPt. When trace haematuria and moderate proteinuria were combined, both the sensitivity, specificity and PvPt were all above 90%, giving the best overall values in all the combinations made. PMID- 1452993 TI - Abundance/host size relationship in a fish trematode community. AB - The abundance of six species of trematodes: Aphanurus stossichi, Bacciger israelensis, Diphterostomum israelense, Plagioporus idoneus, Leprocreadium album and L. pegorchis, parasitic in the digestive tract of marine teleostei (Sparidae) collected near Jounieh (east Mediterranean), was analysed as a function of the host-size. In two parasite/host systems, infections were observed from the lowest size classes of the sample, with a clear tendency to an increase of abundance in older fish. In four others, parasites appear only above a rather high threshold class, young individuals never being infected. In the last three parasite/host systems, host invasion may occur early or late, but infection decreases above a well defined size class, old fishes rarely or never being infected. A given trematode species, when parasitizing several host species, shows similar abundance/host size relationships, e.g., P. idoneus in Diplodus vulgaris and Oblada melanura. When more than one species of trematode infects a single host species, curves can be markedly distinct; for instance, L. pegorchis was collected from Pagellus erythrinus below 15 cm. whereas D. israelense parasitized the same fish approximately above the same size. There is no evidence that such a replacement of one trematode by another in the course of host growth is a result of inter-specific competition. PMID- 1452994 TI - A hidden break in the 28.0S rRNA from Diphyllobothrium dendriticum. AB - Nondenatured and denatured total RNA from the tapeworm Diphyllobothrium dendriticum (Cestoda) was analysed by agarose gel electrophoresis. It was found that the large subunit ribosomal RNA (lrRNA) is 28.0S and the small subunit ribosomal RNA (srRNA) is 19.5S. Following denaturation the 28.0S rRNA was disrupted into a 19.5S subfragment and a 20.7S subfragment due to the presence of a centrally located hidden break. By hybridization of Northern blot membranes with oligonucleotide probes specific for the 5'- and 3'-ends of the lrRNA respectively, we have shown that the 19.5S subfragment is from the 5'-end (the alpha-subfragment) and the 20.7S subfragment from the 3'-end (the beta subfragment) of the 28.0S rRNA of D. dendriticum. PMID- 1452995 TI - Experimental infection with Taenia saginata (Poland strain) in Taiwanese pigs. AB - Two 22-day-old Landrace-Small Ear Miniature (L-SEM) pigs, five 45 to 66-day-old Small Ear Miniature (SEM) pigs, and one 16-day-old Holstein calf were each fed 1000, 3000 or 10,000 Taenia saginata (Poland strain) eggs respectively and killed 34-77 days after inoculation. Four of the five SEM pigs and the Holstein calf were susceptible to this parasite. However, two L-SEM pigs and one SEM pig remained negative. The cysticerci recovery rates for the SEM pig and Holstein calf were 36% and 3%, respectively. All cysticerci from the SEM pigs were found in the livers, more in the parenchyma (89%) than on the surface (11%). Only eleven cysticerci in two SEM pigs were mature and the remainder were either immature, degenerated or calcified. The cysticerci in the calf were distributed throughout the body: leg muscles (248), heart (27), tongue (17), intercostal muscles (14), diaphragm (5), kidney (1) and liver (1). Most (299) of the cysticerci were mature, one was immature and 13 were degenerated or calcified. The length, width, diameter of the protoscolex and sucker of the cysticerci from the calf were larger than those from the SEM pigs. However, the diameter of the rostellum of the latter was slightly larger than the former. Hooklets were not found on any mature cysticercus recovered. The results of the present study provide evidence that the SEM pig can be used as an experimental intermediate host for T. saginata. PMID- 1452996 TI - Influence of desiccation of faeces on survival and infectivity of first-stage larvae of Muellerius capillaris and Neostrongylus linearis. AB - First-stage larvae of pure strains of M. capillaris and N. linearis (Nematoda: Protostrongylidae) from goats were used to assess the influence of rapid desiccation on survival. M. capillaris survived desiccation of faeces better than N. linearis. The latter species was particularly susceptible to duration of storage after desiccation (0 to 10 days). Surviving larvae of desiccated batches of M. capillaris were less able to infect the land-snail Candidula intersecta. Resistance of first-stage larvae to desiccation is a key factor in infectivity and may partly account for the geographical distribution of the two species of protostrongylids. PMID- 1452997 TI - Experimental infections with Nematodirus spathiger in rabbits. AB - The feasibility of infecting laboratory rabbits experimentally with the ovine nematode Nematodirus spathiger was examined. Eight-week-old rabbits were dosed either with 5000 or with 17,000 third-stage larvae and killed on days 10, 21 or 42 post-infection. With the lower dose, 20 to 40% of the inoculum were recovered at necropsy. Similar values were observed with the 17,000 dose on days 10 and 21 post-infection, but on day 42 the worm population was residual (0.6%). With both dose levels, during the course of infection, the worm populations were mainly composed of fourth-stage larvae and worm egg excretion was low. N. spathiger mainly inhabited the proximal jejunum. The results were compared with N. spathiger infection in sheep to assess the usefulness of the rabbit as an experimental model for Nematodirus infection. PMID- 1452998 TI - A longitudinal study of porcine serological responses to experimental infections with T-1 and T-3 Spanish Trichinella isolates. AB - Comparison of antibody response and antigen recognition was made by ELISA and western-blot analysis in pig experimental infections by T-1 and T-3 Spanish Trichinella isolates. Two groups of Iberian pigs were experimentally infected with 150 larvae/kg body weight of GM-1 and C-76 Spanish Trichinella isolates as representatives of T-1 and T-3 gene pools respectively. Antibody levels and antigen recognition were measured on days -14, 0, 6, 16, 20, 27, 34, 49, 63 and 82 after infection by ELISA and western-blotting assays. Antibody response against C-76 infection was significantly delayed and lower than against GM-1. The two Trichinella isolates were indistinguishable, however, by western blotting analysis, although recognition of larval antigens was quantitatively higher than adult ones. Interestingly, the principle larval antigenic components recognized by pigs were those recognized by the monoclonal anti-sera NIM-M1. Finally, there were no serological patterns indicative of the stage of infection ("antibody windows") discriminating, for example between early versus late infections. PMID- 1452999 TI - Acanthocephalan infection in man in northern Nigeria. AB - Acanthocephalan ova, indistinguishable from the ovoid eggs of Moniliformis moniliformis, were detected in the stools of a 45-year-old man at the University of Jos Health Clinic, Nigeria. The patient complained of general body weakness, occasional giddiness and intermittent burning sensations around the umbilicus. Successful treatment with niclosamide and the possible source of infection are communicated. PMID- 1453000 TI - Ultrastructural localization of bcl-2 protein. AB - Previous cell subfractionation studies have indicated that bcl-2 is an inner mitochondrial membrane protein. We have sought to determine the ultrastructural localization of bcl-2 protein in lymphoma and breast carcinoma cell lines and biopsy material known to overexpress bcl-2 using immunoelectron microscopy. To avoid the possibility of processing artifacts, samples were prepared by three different methods: progressive lowering of temperature, cryosectioning, and freeze-substitution. In all instances the labeling of bcl-2 protein was relatively weak but the distribution the same. In both lymphoma and breast carcinoma tissues, bcl-2 protein was detected on the periphery of mitochondria: little labeling of either the mitochondrial matrix or cristae could be detected. Labeling was also detected on the perinuclear membrane and throughout the cytoplasm, as also indicated by confocal microscopy. These data therefore indicate that bcl-2 protein can be detected at several intracellular sites and that at the likely functional destination, the mitochondria, there appears to be, contrary to expectations, a preferential association with the outer membrane. PMID- 1453001 TI - GRAMP 100: a membrane protein concentrated on secretory granule membranes and the apical cell surface in exocrine acinar cells. AB - Using a monoclonal antibody (SG10A6) raised against secretion granule membranes of the rat parotid gland, we have identified an antigen that is a common component of both exocrine pancreatic and parotid granule membranes. SG10A6 (an IgM) immunoprecipitates antigen that migrates as a single band (M(r) approximately 80 KD unreduced; M(r) approximately 100 KD reduced) and immunoblots at least two polypeptides that are similar to the reduced and nonreduced immunoprecipitated antigen. This granule-associated membrane polypeptide (GRAMP 100; named for the apparent M(r) in reduced form) is also a prominent component of plasma membrane fractions. Immunocytochemical localization at the electron microscopic level demonstrates the presence of GRAMP 100 on granule membranes, especially condensing vacuoles and exocytotic figures, and the apical plasma membrane. Lower levels of antigen are detected on basolateral plasma membrane and on peri-Golgi membranes that may be part of the endosomal system. Both the cell fractionation and immunocytochemical localization indicate that GRAMP 100 differs in distribution from GRAMP 92 and 30K SCAMPs, two other components of exocrine granule membranes identified with monoclonal antibodies. To date, no polypeptides have been identified with this approach that are exclusive components of exocrine granule membranes. PMID- 1453002 TI - Immunoelectron microscopic localization of phosphoproteins associated with the mitotic spindle. AB - We examined the immunogold staining of microtubules and microtubule organizing centers using an improved silver-enhancement reagent for small (1-1.4 nm) gold conjugated secondary antibodies. First, the staining properties of different commercial preparations of gold-labeled antibodies were compared for sample penetration, label uniformity, and labeling density, and Nanogold 1.4-nm gold conjugated F(ab') was found to be superior to the other probes examined. However, in samples examined for the localization of alpha- and beta-tubulin, gold staining did not extend through the pericentriolar material nor were the centrioles labeled. This apparent lack of centrosomal staining was not due to problems associated with penetration of the antibody probes, since staining adjacent to and within the centriolar cylinder was observed when phosphoprotein antigens recognized by the MPM-2 antibody were localized. The MPM-2 antibodies also localized to mitotic kinetochores, kinetochore fibers, and midbodies, in addition to mitotic centrosomes. The level of MPM-2 staining of the centrosome varied through the cell cycle. At interphase, this staining was restricted within the centriolar cylinder, whereas in mitotic cells extensive staining throughout the pericentriolar material was also observed. These results established the close relationship of MPM-2-reactive phosphoproteins with the centrosome, and suggest that this technique may be useful for ultrastructural localization of other cytoskeletal proteins. PMID- 1453003 TI - Silver enhancement of gold antibody probes in pre-embedding electron microscopic immunocytochemistry. AB - In pre-embedding EM immunocytochemistry with gold probes, the gold must be small enough to penetrate through cell membranes treated with mild detergents. Antibodies labeled with small gold probes (1-1.4 nm) are too small to be resolved in thin sections but can be seen if they are silver-enhanced after the gold has bound to the antigens in the cells. We investigated several aspects of gum arabic silver lactate-hydroquinone enhancement solution (Danscher solution) by examining gold-conjugated antibodies embedded in agar, sectioned on a vibrotome, and enhanced with different solutions. The rate of silver enhancement was optimized in 50% gum arabic and 200 mM HEPES buffer, pH 5.8. We also examined chemicals used as developers and found that N-propyl gallate (NPG) gave a more uniform development than the routinely used hydroquinone (HQ). The diameter of the silver enhanced particles after incubation in osmium tetratoxide (OSO4) decreased somewhat with longer incubation time and higher percentages, but the density (number per unit area) of silver-enhanced particles was little changed. The loss of silver-enhanced particle diameter was reduced by lowering the concentration of OSO4 to 0.1%. Comparison of commercial small gold probes showed that NPG enhancement of Nanogold gave more uniform particle size and a better correlation between enhancement time and particle density. When this procedure was applied to cell cultures with monoclonal antibodies, the silver-enhanced particles were similar to those in the agar sections. When free-floating tissue sections were used, longer silver enhancement times were needed to obtain similarly sized particles. This new NPG-silver-enhancement procedure offers a reliable and easy method to localize proteins in cultured cells and tissue sections by pre embedding electron microscopic immunocytochemistry. PMID- 1453004 TI - Immunohistochemical localization of carbonyl reductase in human tissues. AB - Carbonyl reductase, an NADPH-dependent oxidoreductase of broad specificity, is present in many human tissues. Its precise localization, however, has remained unclear, as well as its physiological and possible pathophysiological significance. The present study reports the immunohistochemical localization of the enzyme in normal human tissues. Immunostaining was detectable in all organs investigated. The highest concentrations were found in the parenchymal cells of the liver, the epithelial cells of the stomach and small intestine, the epidermis, the proximal tubules of the kidney, neuronal and glial cells of the central nervous system, and certain cells of the anterior lobe of the pituitary gland. Consistently pronounced staining was also observed in smooth muscle fibers and the endothelium of blood vessels. The results are in agreement with a housekeeping function of carbonyl reductase in the elimination of reactive carbonyl compounds. PMID- 1453005 TI - Immunocytochemical and biochemical demonstration of formaldhyde dehydrogenase (class III alcohol dehydrogenase) in the nucleus. AB - Alcohol dehydrogenase (ADH), the major enzyme catalyzing the biological oxidation of ethanol in mammals, includes four classes with very different capacities for ethanol oxidation. Class III ADH is present in all the tissues and is well conserved throughout evolution. This enzyme has a low activity with ethanol, is specific for the glutathione-dependent oxidation of formaldehyde, and is therefore a formaldehyde dehydrogenase (FALDH). Until now there have been few and conflicting studies concerning its intracellular distribution, which is important for the understanding of its role in cell function. In the present work we used biochemical and immunocytochemical methods to assess the distribution of FALDH in rat hepatocytes and astroglial cells. With the glutathione-dependent formaldehyde dehydrogenase assay, we found the highest activity in the cytosol of hepatocytes and brain cells (12 and 2.6 mU/mg protein, respectively), but nuclei also exhibited significant activity (1.16 and 2.1 mU/mg protein, respectively). The immunocytochemical results showed the presence of FALDH binding sites in both the cytoplasm and the nucleus of the different cell types studied. Whereas no specific gold particle labeling was seen associated with any cytoplasmic component, in the nucleus the particles were found mainly over condensed chromatin and interchromatin regions. Finally, the gold particle density over both the nucleus and cytoplasm was greater in differentiated than in proliferating astrocytes in primary culture. In contrast, class I ADH, primarily responsible for ethanol metabolism, was found only in the cytoplasm of hepatocytes. We propose that one of the functions of FALDH is to protect cell structures, including DNA, from the toxic effects of endogenous formaldehyde, which is an intermediate in many metabolic process. PMID- 1453006 TI - Iron content correlates with peroxidase activity in cysteamine-induced astroglial organelles. AB - A subpopulation of astrocytes in periventricular brain regions and in cysteamine treated neuroglial cultures contains cytoplasmic granules that exhibit an affinity for Gomori stains, orange-red autofluorescence, and non-enzymatic peroxidase activity. The autofluorescence and pseudoperoxidase activity are consistent with the presence of porphyrins and heme iron, respectively. In the present study, we employed diaminobenzidine cytochemistry, transmission electron microscopy, and energy-dispersive X-ray microanalysis (electron microprobe) in an attempt to correlate fine structure with the peroxidase activity and elemental composition of the cysteamine-induced inclusions in cultured astrocytes. In osmicated preparations, these membrane-bound inclusions varied greatly in size, were round or ovoid in shape, and exhibited an intensely electron-dense granular matrix. In non-osmicated preparations, many inclusions exhibited internal membranous partitions producing complex subcompartmentalization. Diaminobenzidine reaction product, indicative of endogenous peroxidase activity, was occasionally observed distributed diffusely throughout the granule matrix. More commonly, peroxidase activity was restricted to specific intraorganellar compartments. Elemental iron was detected in the inclusions by electron microprobe analysis. The presence and concentration of iron in these organelles correlated closely with the presence and intensity of diaminobenzidine staining, suggesting that redox-active iron mediates the pseudoperoxidase reactions in these cells. Cysteamine-induced derangements of porphyrin-heme biosynthesis may be responsible for the proliferation of iron-containing gliosomes in these astrocytes. PMID- 1453007 TI - Immunocytochemical localization of 67 KD Ca2+ binding protein (p67) in ventricular, skeletal, and smooth muscle cells. AB - By using immunocytochemical techniques, we examined the localization of a 67 kDa Ca2+ binding protein (p67) and calpactin I heavy chain (p36) in ventricular myocytes, skeletal myocytes, and intestinal smooth muscle cells. Immunofluorescence microscopy revealed that the p67 was expressed in all these muscle cells, whereas anti-p36 antibody stained cells in connective tissues but failed to stain these muscle cells. Immunogold electron microscopy was carried out to examine the subcellular localization of the p67 in muscle cells. The results showed that the p67 was exclusively confined to the plasma membrane of muscle cells and the presumptive transverse tubules of the striated myocytes. Immunoblot analysis with anti-p67 antibody showed that the p67 was indeed a constitutive protein of the sarcolemma isolated from rat hearts. These results indicate that the p67 is a sarcolemma-associated Ca2+ binding protein expressed in both striated myocytes and intestinal smooth muscle cells. PMID- 1453008 TI - Ecto-calcium-dependent ATPase activity of mammalian taste bud cells. AB - Histochemistry was utilized to characterize Ca-ATPases associated with lingual taste buds in the golden hamster. Taste buds showed elevated staining for magnesium- or calcium-dependent ATPase (Ca-ATPase) relative to the surrounding epithelium. At low calcium concentrations (0.1-0.5 mM), intracellular staining predominated. Most of the studies were conducted at calcium concentrations of > or = 10 mM, in which most of the staining was localized to the external face of plasma membranes of taste bud cells (including receptor and basal cells) located in the core of fungiform taste buds, or the entire vallate or foliate taste buds. The peripheral fungiform taste bud cells stained much less intensely, but the peripheral cells adjacent to the core showed intermediate levels. GTP and ITP were just as effective substrates as ATP. Millimolar concentrations of magnesium were as effective as calcium. Inhibitors of intracellular ATPases, including quercetin, sodium azide, and 2,4-dinitrophenol, had no effect on the staining. Therefore, the Ca-ATPase staining of plasma membranes at mM concentrations of calcium is thought to correspond to one or more ecto-Ca-ATPase activities with unknown functions. Roles related to increased energy requirements or to the possible function of ATP as a neurotransmitter or -modulator are proposed. PMID- 1453009 TI - Quantitation of gold labeling and estimation of labeling efficiency with a stereological counting method. AB - The amount of immunolabeling over a cell compartment of an average cell was estimated by use of an adaptation of the double disector method introduced by Gundersen. The first and last sections of a stack of ultra-thin sections formed a disector in which cell number could be estimated and related to a defined reference volume to give the cell density. Another stack section, selected at random, was immunolabeled and the number of gold particles associated with unit volume reference space (gold "density") estimated in quadrats placed systematically across the section. The ratio of gold density to cell density was used to estimate the number of gold particles lying over a chosen compartment of an average cell, N(gold)/N(cell). Such estimates required neither cell volume nor section thickness measurement and were reproducible. By combining the number of gold particles per cell with estimates of the number of protein antigens per cell, the number of gold particles associated with each antigen could be found (labeling efficiency). PMID- 1453010 TI - Lectin binding sites as markers of neonatal porcine uterine development. AB - To identify lectin binding sites and to determine if lectin binding patterns change with age in developing neonatal porcine uterine tissues, gilts (n = 3/day) were hysterectomized on Day 0 (birth), 7, 14, 28, 42, or 56. Lectin binding was visualized in Bouin's-fixed uterine tissues with seven biotinylated lectins (ConA, DBA, PNA, RCA-I, SBA, UEA-I, and WGA) and avidin-peroxidase staining procedures. Lectin specificities were demonstrated by pre-incubating lectins with appropriate inhibitory sugars (0.2 M). Staining intensity was evaluated visually (absent, weak, moderate, or strong) for three endometrial tissues; luminal epithelium, glandular epithelium, and stroma. Staining intensities for DBA, PNA, SBA, and WGA were not affected by neonatal age. Staining with these lectins was greater in uterine epithelium (moderate or strong) than in stroma (weak). In contrast, binding patterns for ConA, UEA-I, and RCA-I were affected by neonatal age. Strong epithelial staining associated with ConA binding was observed on all days, whereas stromal ConA staining decreased in intensity from moderate to weak after Day 14. Epithelial staining with UEA-I increased from moderate to strong after Day 28, whereas stromal UEA-I staining decreased from moderate to weak after day 28. Staining with RCA-I was homogeneous for luminal epithelium and stroma but variegated for glandular epithelium on and after Day 7. These observations indicate that a variety of lectin binding sites are present in developing neonatal porcine endometrial tissues and that developmentally related alterations in the distribution and/or orientation of glycoconjugates containing alpha-D-mannose, beta-D-galactose, beta-D-acetyl-N-galactosamine, and alpha-L fucose residues occur between birth and Day 56 as these tissues mature. PMID- 1453011 TI - The human erythropoietin receptor. AB - Molecular analysis of the human erythropoietin receptor (EpoR) promises to yield a greater mechanistic understanding of erythropoiesis and disease states that affect red cell production. The cloned receptor molecule is a 66 kDa membrane protein that is structurally related to a large superfamily of haemopoietin/growth factor receptors. The 66 kDa EpoR alone is capable of binding to erythropoietin (Epo) with nanomolar affinity. The native EpoR may form dimers before or after binding Epo. EpoR dimers and/or associated molecules are probably necessary for high-affinity Epo binding. The 66 kDa EpoR probably exists as a protein complex with as yet unidentified proteins of 100 and 85 kDa. The molecular mechanism of Epo signal transduction remains largely undefined. The possible role of the EpoR in human diseases has been studied in a variety of clinical conditions. A structurally abnormal EpoR gene has been identified in a human erythroleukemia cell line. In polycythemia vera, red cell progenitors exhibit exaggerated sensitivity to Epo and express only low-affinity EpoR. Some cases of hereditary polycythemia may be due to a mutant EpoR conferring enhanced Epo sensitivity. Other pathologic conditions may also be associated with abnormalities of the EpoR or its associated molecules. Soluble, immunoreactive EpoR is detectable in human serum, but its physiological significance is unknown. PMID- 1453012 TI - In vitro revelations of aplastic anemia. AB - Aplastic anemia (AA) is a most difficult disease to study in vitro. By the time the disease presents, the marrow is already hypocellular and the peripheral blood shows pancytopenia, leaving little material remaining for study. However, an understanding of its pathogenesis could provide insight into the control of normal hemopoiesis since AA is an in vivo manifestation of failure of normal hemopoiesis and may provide a way of examining stromal cell-stem cell relationships. Recent interest in the pathogenesis of AA has resulted from a) new laboratory techniques, such as stem cell purification used with modifications of the long-term bone marrow culture system and analysis of stem cells at the molecular level with X-linked DNA probes, and b) the availability of recombinant human hemopoietic growth factors (HGF) in large quantities. Consequently, analyses of the function of some of the individual components of stromal cell mediated hemopoiesis in AA patients have been performed. This has been paralleled, and in some instances preceded, by clinical trials of HGF in patients with AA. PMID- 1453013 TI - SCL and related hemopoietic helix-loop-helix transcription factors. AB - The helix-loop-helix (HLH) proteins are a family of transcription factors that include proteins critical to differentiation and development in species ranging from plants to mammals. Five members of this family (MYC, SCL, TAL-2, LYL-1 and E2A) are implicated in oncogenic events in human lymphoid tumors because of their consistent involvement in chromosomal translocations. Although activated in T cell leukemias, expression of SCL and LYL-1 is low or undetectable in normal T cell populations. SCL is expressed in erythroid, megakaryocyte and mast cell populations (the same cell lineages as GATA-1, a zinc-finger transcription factor). In addition, both SCL and GATA-1 undergo coordinate modulation during chemically induced erythroid differentiation of mouse erythroleukemia cells and are down-modulated during myeloid differentiation of human K562 cells, thus implying a role for SCL in erythroid differentiation events. However, in contrast to GATA-1, SCL is expressed in the developing brain. Studies of the function of SCL suggest it is also important in proliferation and self-renewal events in erythroid cells. PMID- 1453014 TI - Characteristics of the hematopoietic stem cell compartment in adult mice. AB - Mouse hematopoietic stem cells can be enriched from adult bone marrow by a number of methods. The resulting cell populations are heterogeneous in function, suggesting a complex organizational structure within the stem cell compartment. Several assays can be applied to the study of early stages of hematopoiesis; however clonal assays for long-term repopulation, the most critical operational definition of hematopoietic stem cells, are lacking. Further complicating the prospect of understanding early hematopoiesis is the finding that genetic variations among laboratory strains of mice lead to major differences in phenotypic and functional characteristics of hematopoietic stem cells. Application to the human situation of the methodology developed for stem cell isolation and characterization in the mouse will be hampered by the possibility of genetic variations among human subjects and the lack of a well-characterized assay system to detect and quantify cells capable of long-term repopulation of irradiated recipients. PMID- 1453015 TI - Retinyl acetate and all-trans-retinoic acid enhance erythroid colony formation in vitro by circulating human progenitors in an improved serum-free medium. AB - Retinyl acetate (RA) dramatically increased the production of early (d16) erythroid colonies in vitro by circulating human progenitor cells growing in an improved serum-free (SF) medium. In the absence of either erythropoietin (Epo) or insulin-like growth factor I (IGF-I), RA alone was able to induce the hemoglobinization of cells in these erythroid colonies. RA synergized with Epo or with IGF-I to yield increased numbers of well-hemoglobinized early colonies. In the presence of defined burst promoting activity (BPA) provided by recombinant human interleukin 3 (rHuIL-3) and hemin, RA and all-trans-retinoic acid (ATRA) were identical with respect to their differentiation-inducing function for early erythroid colonies. ATRA increased the number of these colonies in a concentration-dependent manner, with maximal stimulation (3.5-fold) occurring at 30 nM in the presence of 5.5 ng/ml IL-3, 0.1 mM hemin, 3.0 U/ml Epo and 30 nM IGF I. This appears to be the first demonstration of erythropoietic activity of two metabolic derivatives of vitamin A in SF medium. PMID- 1453016 TI - Clonogenic assay is not predictive but reflects therapeutic efficacy of interferons in the treatment of chronic myelogenous leukemia. AB - Patients with chronic myelogenous leukemia (CML) have been treated with interferon (IFN) alpha-2b alone or in combination with IFN gamma. In order to predict clinical response to IFN, bone marrow samples from 15 CML patients were incubated with serial dilutions of IFN alpha-2b to obtain the IC50 values for erythroid burst forming units (BFU-E) and granulocyte-macrophage colony forming units (CFU-GM). A dose-dependent inhibition of at least one lineage was observed in all but one sample. An inhibitory effect of greater than 50% was reached for BFU-E in 8/14 patients and for CFU-GM in 10/14 patients. All three patients with no response (NR) to IFN treatment had IFN-sensitive BFU-E and CFU-GM. In four patients with hematologic remission (HR) or partial hematologic remission (PHR), BFU-E or CFU-GM were affected very little by the inhibitory effect of IFN. These observations suggest no predictive value for pretesting IFN sensitivity in vitro. The in vivo effect of IFN on the hemopoietic progenitor cells BFU-E and CFU-GM was evaluated in patients treated with either IFN alpha-2b alone (n = 11), or in combination with low dose IFN gamma (n = 10). All patients were newly diagnosed and not pretreated. After a median treatment duration of 11 months (range 3-25) a significant decrease in BFU-E and CFU-GM was observed in both groups of patients. We conclude that in vitro colony growth reflects the therapeutic efficacy of IFN. PMID- 1453017 TI - Dynamic changes in cytokine secretion by stromal cells during prolonged maintenance under protein-free conditions. AB - Stromal cells of bone marrow origin produce a variety of known cytokines and some factors exhibiting apparently new biological activities. Several of these were identified by the study of cell to cell interactions and were not found in detectable amounts in media conditioned by the cells. We describe here a culture system that enables the release of stromal cytokines into medium free of any added proteins and supplemented with peptides from casein hydrolysate (0.1%). The absence of serum proteins allows extensive concentration and monitoring of activities that are otherwise undetectable. Stromal cells of the MBA-2.1 clonal cell line were seeded in a stationary bed reactor packed with a carrier of non woven fabric matrix. After a proliferation phase with serum containing medium, the cells were maintained for over 10 months in protein-free medium. Throughout this extended incubation in the absence of serum or serum replacing proteins, stromal cells retained their viability and continuously released transforming growth factor-beta (TGF-beta), macrophage-colony stimulating factor (M-CSF) and restrictin-P, a cytotoxic factor that specifically arrested the growth of plasmacytoma cells. In addition, interleukin-6 (IL-6) was first undetectable, and later in culture its titer reached a maximum of 180,000 international units (IU)/ml. Concomitantly, the production of restrictin-P diminished and reached its lowest levels at the end of 10 months. The results may imply a possible causal relationship between the expression of IL-6 and restrictin-P, since no similarly significant changes were observed in the titers of M-CSF and TGF-beta. This novel bioreactor system may be adaptable for efficient production of different cytokines under absolute serum-free conditions. PMID- 1453018 TI - Primary reconstruction of the mandibular alveolar ridge following resection. AB - Standard techniques of mandibular reconstruction aim at the restoration of function. However, the height and shape of the alveolar ridge are often neglected and reconstruction often results in difficulty in subsequent denture wear. Immediate reconstruction of the alveolar process with particulate autologous iliac bone is described, a technique used in 10 patients since 1978. PMID- 1453019 TI - A nasal vestibular flap for reconstruction of the upper lip. AB - A technique to reconstruct the hair-bearing upper lip by means of a hair-loaded nasal vestibular flap is described. This flap is elevated from the nasal vestibular area, and does not result in nasal deformity. This flap is especially suitable to reconstruct the medial portion of the hair-bearing upper lip in adult males. PMID- 1453020 TI - Midline cervical cleft. A case report. AB - A case of incomplete midline cervical cleft of the upper neck is reported. It showed histological resemblance to a mature teratoma with three different germ cell components, including cartilage, striated muscles, small salivary glands, and nerves. PMID- 1453021 TI - The use of fresh frozen allogeneic bone for maxillary and mandibular reconstruction. AB - The use of fresh frozen bone (FFB) alone, or in combination with autogenous bone (AB), for bony augmentation of the maxilla and mandible in preparation for dental reconstruction with endosseous implants has been studied. Ten patients received FFB +/- AB for augmentation of a severely atrophic mandible (n = 6) or for reconstruction of a jaw defect secondary to trauma or tumor resection (n = 4). Average follow-up was 26.3 +/- 5.4 months. At the time of implant placement, the bone grafts were found to be firm in consistency, well incorporated, and well vascularized in all 10 patients. Twenty-nine endosseous implants were placed an average of 8.3 +/- 3.1 months following bone grafting. One implant failed and was replaced, and one implant remains buried as a nonfunctional unit. All patients have been restored prosthetically by means of 28 of the 29 implants. This preliminary study indicates that FFB may be used alone or in combination with autogenous bone for augmentation or reconstruction of the atrophic maxilla and mandible. The resultant ridge is adequate to support loaded endosseous implants. A potential disadvantage is the minimal risk of disease transmission. PMID- 1453022 TI - Endosseous implants in the irradiated composite radial forearm free flap. AB - This paper describes the application of endosseous titanium implants that have been inserted into the vascularized bone of the radial forearm composite flap, used for mandibular reconstruction. The technique described allows full orofacial rehabilitation to be achieved, following ablative surgery and adjuvant radiotherapy. PMID- 1453023 TI - Long-term clinical and radiologic evaluation of autotransplanted teeth. AB - The purpose of the present study was to investigate the radiologic results of 40 autotransplantations (20 molars and 20 premolars) performed in the orthodontic department of the University of Geneva between 1979 and 1990. The sample demonstrated persistence of pulp vitality and continuous root development, followed, however, in most cases by replacement root resorption. The data were in accordance with previously published studies and point to an ideal developmental stage for molar and premolar transplantation to ensure pulpal and periodontal survival. PMID- 1453024 TI - Shoulder-arm-syndrome after radical neck dissection: its relation with the innervation of the trapezius muscle. AB - In a clinical and electromyographic follow-up of 54 patients who underwent radical neck dissection, vast differences in the individual severity of the shoulder-arm-syndrome were found: 31% experienced severe limitations of shoulder mobility combined with severe pain, whereas 41% suffered only mild discomfort and 28% were free of complaints. These clinical findings were compared to recent anatomical observations concerning individual patterns of innervation of the trapezius muscle. It could be shown that the role of the cervical plexus in the innervation of the trapezius muscle is of great importance and that its subfascial branches are able to maintain the motor supply following radical neck dissection in about 2/3 of patients. PMID- 1453025 TI - Extensive malignant schwannoma of the mandibular nerve. Case report. AB - An extensive malignant schwannoma of the mandibular nerve in an 8-year-old boy is presented. The clinical presentation, light microscopic findings, and radiographic features are described. The patient was successfully treated with surgery in combination with chemotherapy. He is still well, without evidence of metastasis or local recurrence, 5 years postoperatively. PMID- 1453026 TI - Breast angiosarcoma metastatic to the maxillary gingiva. Case report. AB - A case of breast angiosarcoma metastatic to the maxillary gingiva is reported. A review of the literature revealed only three previously reported cases. Angiosarcomas often present as benign lesions. The surgeon should maintain a high level of vigilance when patients present with oral lesions and a history of breast tumor. PMID- 1453027 TI - Second reconstruction of the posterior maxilla with a free latissimus dorsi muscle flap. Case report. AB - This paper reports a case in which a latissimus dorsi free muscle flap was used for a second reconstruction following resection of a maxillary ameloblastoma when the ipsilateral temporalis muscle flap had already been used. The case illustrates the dilemma of immediate versus delayed reconstruction following excision of maxillary tumours. PMID- 1453028 TI - Intraosseous hemangioma of the zygomatic bone. A case report. AB - Intraosseous hemangiomas of the facial skeleton are infrequently seen, with most cases occurring in the mandible and maxilla. Hemangioma of the zygomatic bone, however, is extremely rare. A case is presented in which selective embolization, resection of the tumor, and immediate reconstruction were carried out. PMID- 1453029 TI - Esthesioneuroblastoma. A case report. AB - Esthesioneuroblastoma (ENB) is a rare neuroectodermal tumor originating from the olfactory mucosa and therefore usually arising from the nasopharynx. A case in which the diagnosis was made in connection with the extraction of a tooth is reported. Manifestation in the dento-alveolar region is unusual for this tumor. The case presented is also unusual in that the classic symptoms of ENB were not present. Diagnosis, classification, and therapy are described with a brief review of the literature. PMID- 1453030 TI - Malignant lymphoma presenting as pericoronitis. A case report. AB - A case of diffuse, large-cell non-Hodgkin's lymphoma presenting as pericoronitis in the oral cavity is described. The diagnostic pitfalls are briefly discussed. PMID- 1453031 TI - Central schwannoma of the maxilla. AB - A case of schwannoma in the maxilla associated with the nasopalatine nerve of a 9 year-old boy is reported. The diagnosis is supported by an immunohistochemical demonstration of S-100 protein within the tumor cells. The patient is free of disease 6 years after tumor removal. PMID- 1453032 TI - Does metronidazole prevent alveolitis sicca dolorosa? A double-blind, placebo controlled clinical study. AB - The effect of a single preoperative dose of metronidazole in the prevention of alveolitis sicca dolorosa (ASD) after surgical removal of one impacted, non infected mandibular third molar was investigated. A patient sample of 270 were given either 1000 mg of metronidazole or placebo at least 30 min before surgery. The preoperative recordings included gender, age, tooth to be removed, experience of surgeon, time of test medication, and duration of surgery. No difference was found between the metronidazole and placebo groups in the occurrence of ASD. The duration of surgery and the experience of the operating surgeons had no effect on the occurrence of ASD. The present study failed to demonstrate any preventive effect of a single dose of metronidazole on the development of ASD. PMID- 1453033 TI - Sagittal split osteotomy fixed with biodegradable, self-reinforced poly-L-lactide screws. A pilot study in sheep. AB - Self-reinforced poly-L-lactide (SR-PLLA) screws were used to fix bilateral mandibular sagittal split osteotomies (SSO) in six sheep. No intermaxillary fixation was used postoperatively. The follow-up time was 16 weeks, after which the sheep were killed. Both sides of the mandible were photographed and radiographed. The bending strength of the osteotomy was measured on the left side of the mandible. Histological and microradiographic studies were performed on the right side of the mandible. The results showed that the SR-PLLA screws were strong enough to fix the SSO rigidly. The bending force needed to break the bone was greater than that for the average unoperated mandible. The histological and microradiographic studies showed uneventful healing of the osteotomies in all six sheep. The results indicate that this method should be suitable for rigid fixation of SSO and fractures of the mandible in human beings. PMID- 1453034 TI - Muscle spindles in the mylohyoid muscle of rats. AB - The mylohyoid muscle has several functions in relation to respiration, deglutition, and phonation, but these functions are not fully understood. The interaction of the mylohyoid nerve and muscle in 25 rats was studied by neurophysiologic and histologic methods. Stretching of the muscle elicited electrical responses from the branch of the mylohyoid nerve innervating the mylohyoid muscle, and stretch-sensitive receptors were demonstrated histologically in the mylohyoid muscle. This study indicates that the mylohyoid muscle plays an active role in functions such as swallowing, breathing, and phonation. PMID- 1453035 TI - Application of the condylar positioning appliance in mandibular sagittal split osteotomies with rigid skeletal fixation. AB - During orthodontic-surgical treatment of dentofacial deformities, centric relation of the mandibular condylar head to the fossa articularis must be maintained. Intraoperative application of the condylar positioning appliance, in combination with different surgical splints, allows three-dimensional adjustment of the jaw segments. The condylar positioning appliance can be used in osteotomies of the mandible alone, in isolated Le Fort I osteotomies, or in simultaneous osteotomies of the maxilla and mandible. PMID- 1453036 TI - Electrognathographic patterns of mandibular motion after bilateral vertical ramus setback osteotomy. AB - The purpose of this investigation was to study, by means of an electrognathographic procedure, mandibular motion after bilateral vertical ramus osteotomy for correction of mandibular prognathism in 27 adults. Each patient had kinesiographic registrations taken within 1 week before the operation and 6 months postsurgery. The results of the study demonstrated that, on average, orthognathic surgery did not adversely affect the postoperative mandibular motion. On the contrary, postoperative improvement in most of the variables was revealed by analysis of postoperative changes and comparison of the postoperative values with normative data. PMID- 1453037 TI - Disfigurement and psychosocial handicap of adults with extreme mandibular prognathism. AB - Questionnaires and psychological tests were used to assess the psychosocial impact of mandibular prognathism. Patients with mandibular prognathism were asked to assess the impediments caused by their dentofacial deformity. In addition, they were asked to rate their appearance and to report the effect that it had on their social contacts. The self-assessment revealed that patients felt esthetically impaired, but that they had a fairly positive autostereotype, as revealed by their self-descriptive choices on a personality scale. These results were compared with the assessments made by two different control groups composed of persons with no esthetic impairment. The attitudes of the control groups toward the patients were more negative than perceived by the patients, indicating that mandibular prognathism does result in a social handicap. PMID- 1453038 TI - Surgically assisted rapid maxillary expansion in adults. AB - Twelve adults with maxillary width discrepancy of greater than 5 mm were treated by surgically assisted rapid maxillary expansion. The procedure consisted of bilateral zygomatic buttress and midpalatal osteotomies combined with the use of a tooth-borne orthopedic device postoperatively. Mean palatal expansion of 7.5 mm (range of 6 to 13 mm), measured in the first molar region, was achieved within 3 weeks in all patients. Expansion remained stable during the 12-month study period, with a mean relapse for the entire group of 0.88 +/- 0.48 mm. Morbidity was limited to mild postoperative discomfort. The results of this preliminary study indicated that surgically assisted rapid maxillary expansion is a safe, simple, and reliable procedure for achieving a permanent increase in skeletal maxillary width in adults. Further study is necessary to document the three dimensional movements of the maxillary segments and long-term stability of the skeletal and dental changes. PMID- 1453039 TI - Severely impacted canines: autotransplantation as an alternative. AB - Although orthodontic repositioning of impacted teeth is widely used, the treatment has its limitations. Autotransplantation is an alternative therapy that may be used in selected cases of severe impaction or when orthodontic repositioning is unsuccessful. Two case reports are presented to illustrate the use of the technique in patients with severely impacted canines. Indications and limitations are discussed. PMID- 1453040 TI - Prevalence and variance of temporomandibular dysfunction in orthognathic surgery patients. AB - Seventy-five patients were studied retrospectively to assess the prevalence and variance of temporomandibular dysfunction in an orthognathic surgery population. Preoperatively, 49.3% of the sample presented with temporomandibular dysfunction. After orthognathic surgery, of the symptomatic patients, 89.1% had improved temporomandibular function after surgery, 2.7% were unchanged, and 8.1% had increased symptoms. Of the patients asymptomatic prior to surgery, 7.9% developed temporomandibular dysfunction postoperatively. Temporomandibular dysfunction was significantly more prevalent in patients with a Class II skeletal deformity than in those with a Class III deformity, and temporomandibular function generally improved in both groups postsurgically. PMID- 1453041 TI - [Effect of coagulation inhibitor proteins (Calphobindins) on tissue factor expression of endothelial cells]. AB - We established a method for measuring procoagulant action on human umbilical vein endothelial cells (HUVEC). HUVEC (2.5 x 10(4)/well) were stimulated with 1 microgram/ml endotoxin (lipopolysaccharide: LPS) for 6 hours at 37 degrees C in 5% CO2. After washing, the HUVEC were incubated with assay buffer containing Proplex ST 1 unit (factor VII)/ml, S2222 0.6 mg/ml and CaCl2 6.6 mM, for 30 minutes at 37 degrees C. The procoagulant activity was determined by measuring the supernatant at OD405. Calphobindin I, II and III (CPB I, CPB II and CPB III) are the calcium dependent phospholipid binding proteins that exhibit anticoagulant activity in vitro. In this study, we investigated the effects of CPB I, CPB II and CPB III on procoagulant activity (PCA) expressed on HUVEC. The results are as follows 1) CPBI inhibits the procoagulant activity on HUVEC in a dose-dependent manner (IC 50% less than 0.4 microM). The same doses (0.4 microM) of CPBII and CPBIII decreased the procoagulant activity to 28.1% (CPBII), and to 84.6% (CPB III). CPB anticoagulant activities were, CPBII greater than CPBI greater than CPBIII, in that order. 2) When 0.05% H2O2 was added to the cell culture medium wells, concentrations of CPBI in supernatants increased in a time dependent manner, and they reached to the maximum after 8 hours. CPBI in supernatants after 24 hours were not detected without H2O2, but concentrations of 4.88 ng/ml/10(4) cells with 0.01% H2O2, and 9.60 ng/ml/10(4) cells with 0.05% H2O2 were detected. PMID- 1453042 TI - [The study of DNA ploidy as a prognostic factor in uterine cervical cancer]. AB - Nuclear DNA content was measured in 410 paraffin-embedded samples from 136 cases (43 stage Ib and 93 stage IIb) of uterine cervical cancer by flow cytometry, and the significance of DNA ploidy for use as a prognostic factor was evaluated. Positive parametrial invasion cases (p less than 0.05), metastasis to pelvic lymph nodes cases and lymphatic vessel permeation form (p less than 0.05) showed a high incidence of DNA aneuploidy. In the study of the relationship between DNA ploidy and prognosis by the Kaplan-Meier method, the DNA aneuploid group showed a tendency to a poor prognosis in all cases, large cell non-keratinizing cases (p less than 0.05), and large cell non-keratinizing pT2b with pelvic lymph nodes metastasis cases (p less than 0.05), and the DNA aneuploid group had significantly lower three- and five-year survival rates (p less than 0.05). PMID- 1453043 TI - [Comparison of YAG and CO2 laser excisional conization for the treatment of uterine cervical neoplasia]. AB - Thirty-nine patients with cervical neoplasia who were treated by CO2 laser excisional conization were compared with a group of 37 patients whose diagnosis and age were similar were treated by YAG laser excisional conization. Every operation in our series was performed on an outpatient basis. The differences between two groups were statistically significant: The CO2 laser group revealed the advantages in the healing periods from treatment to the end of epithelization (p less than 0.01: T test) and irradiation time (p less than 0.001). There was no difference in the blood loss during the operation. Both initial cure rates were 100% during the follow-up period of 21 to 65 months. During and post operations, more patients required additional measures such as sutures for uncontrollable bleeding in the CO2 laser group. In conclusion, both methods are felt to be good diagnostic and also therapeutic procedures for cervical neoplasia on an outpatient basis. PMID- 1453044 TI - [Effect of endothelium-derived nitric oxide and prostaglandins on the endothelium dependent vascular refractoriness to angiotensin II in pregnant rabbits]. AB - Recently we demonstrated that the vascular response to angiotensin II (A-II) was attenuated in an endothelium-dependent manner by using the isolated ring specimen iliac arteries of pregnant rabbits. In this paper we investigated the possibility that three vasoactive substances, thromboxane A2(TXA2), prostacyclin (PGI2), and endothelium-derived nitric oxide (EDNO), might be involved in this refractoriness to A-II during pregnancy, by measuring the changes in the vascular response to A II (pA2, intrinsic activity) of the isolated arterial rings of rabbits before and after the addition of an inhibitor specific for each of these three substances. Sodium ozagrel, TXA2 synthetase inhibitor, decreased the vascular response to A II more in the blood vessels of pregnant rabbits, regardless of whether the endothelium was intact or denuded, than in the blood vessels of non pregnant rabbits. Tranylcypromine, a PGI2 synthetase inhibitor, significantly increased contractility in the blood vessels with intact endothelium of pregnant rabbits (i.a. = 1.39 +/- 0.099, n = 11, mean +/- SEM), compared to that in the blood vessels with intact endothelium of non pregnant rabbits (i.a. = 1.08 +/- 0.090, n = 7). Methylene blue, a guanylate cyclase inhibitor which blocks the effect of EDNO, amplified the vascular response in blood vessels with intact endothelium of both groups, and more intensely in the blood vessels of pregnant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453045 TI - [Development of a fetal breathing movement tracking system using pulsed Doppler ultrasound]. AB - Fetal breathing movements (FBM) form a useful means of monitoring fetal conditions and functional development. To develop a continuous and quantitative FBM monitoring system for clinical use, a non-imaging method using pulsed Doppler was devised. A pulsed Doppler cardiotocograph module was extended to obtain low frequency Doppler signals, by the addition of a 90 degree phase shifter, analog multipliers, quadrature detector, sample and hold circuits and low pass filters, to produce five simultaneous outputs representing movement at depths separated by 1.5cm intervals. These outputs represent the displacement inside tissue at the various depths. Signal processing was executed on a 32-bit computer with an A/D converter. On-line processing by means of a zero-crossing method and off-line arc tangent method with high accuracy displacement estimation were applied for calculation. With this system, FBM was detected as cyclic and regular displacements of a few hundred microns ranging from 0.5 to 1.5Hz. With digital signal processing of 2/3Hz high pass filtering, precise evaluation FBM was possible while rejecting gross movements due to maternal breathing, etc. Although further studies are required for clinical application, it appears that quantitative assessments of FBM should be possible with this technique. PMID- 1453046 TI - [Mass-screening for ovarian cancer by means of transvaginal ultrasonography- study on size of ovary to select subjects requiring second screening]. AB - Mass-screening for ovarian cancer by means of transvaginal ultrasonography has been performed in Aomori Prefecture since 1989. To select appropriate candidates to receive the second screening, the size of 44 normal ovaries removed by surgery and was measured studied on 10,692 ultrasonic pictures recorded on a VTR. The results were as follows: (1) All 44 ovaries were under 40mm. (2) In 3,806 (35.6%) of 10,692 women at the first screening, their ovaries were detected by ultrasonography. This detection rate was higher in young subjects and in the luteal and menstrual phases than in others. (3) Of these ovaries, 1,303 (34.2%) were under 19mm, 1,891 (49.7%) were 20-29mm and 614 (16.1%) were over 30mm in size. (4) The second screening was performed in 472 of the 614 women, and the size of the ovaries in 83 (17.6%) of them was under 29mm. (5) The frequency of ovarian size exceeding 40mm at the second screening, was 12.5% of the 30-39mm diameter group and 48.0% of the 40-49mm group at the first screening. There was no malignant tumor in the former, but there were one pre-malignant and one malignant tumor in the latter. These results indicate that the second screening should be performed for women having ovaries over 40mm in size. PMID- 1453047 TI - [Usefulness of intraperitoneal carboplatin administration-- pharmacokinetic analysis]. AB - A bolus of carboplatin (CBDCA) 200-450mg/body (148-292mg/m2) with 500ml saline was administrated into the abdominal cavity (ip) of 4 patients with ovarian cancer and 2 patients with uterine endometrial cancer, and concentrations of free and total platinum (Pt) in the blood and ascites were measured with the passage of time. Moreover, the results were analyzed with a 2-compartment model and moment analyses in order to study in vivo kinetics of CBDCA at the time of the ip administration. 1) The shift of Pt to blood through ip administration depended on the peritoneal clearance. Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa. The level was lower in the latter group. 2) The non-binding rate of Pt with protein in the ascites at the time of the ip administration was correlated with the CBDCA concentration in the ascites. 3) The non-binding rate was 80% or more both in the ascites and in the blood within 4 hours after ip. The high level of the nonbinding rate appeared to cause prolongation of the presence of the free-Pt in the ascites and blood, especially in patients with peritonitis carcinomatosa. 4) AUC level in blood was equal to or higher than that observed when the same dose was administered iv. The levels of free-Pt and AUC in the abdominal cavity were 2 to 5 times higher than those in blood in patients with a normal peritoneum, and 7 to 14 times higher in patients with peritonitis carcinomatosa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453048 TI - [Transrectal ultrasonographic detection of uterosacral ligaments--preliminary study for ultrasonographic evaluation of endometriosis]. PMID- 1453049 TI - [Invasive hydatidiform mole in the fallopian tube: report of a case]. PMID- 1453050 TI - [A case of prenatal diagnosis on the VATER association]. PMID- 1453051 TI - [A case of rhabdomyoma arising from the ovary]. PMID- 1453052 TI - [Regulatory factors of blood pressure and clinical study of hypertension]. PMID- 1453053 TI - [Clinical study of glomerular diseases]. PMID- 1453054 TI - [clinical study and physiopathology of multiple myeloma]. PMID- 1453055 TI - [Progress on study of calcium metabolism]. PMID- 1453056 TI - [Molecular biological approach to hematologic diseases]. PMID- 1453057 TI - [Osteocytes and bone metabolism]. PMID- 1453058 TI - [Hypercalcemia and hypocalcemia]. PMID- 1453059 TI - [Calcium metabolism and osteoporosis]. PMID- 1453060 TI - [Treatment of digestive system neoplasms by biochemical modulation]. PMID- 1453061 TI - [Stomach cancers and angiotensin II induced hypertension chemotherapy]. PMID- 1453062 TI - [Immunochemical therapy of stomach neoplasms]. PMID- 1453063 TI - [Cytokine therapy of neoplasms]. PMID- 1453064 TI - [Combined radio-chemotherapy of progressive esophageal cancers]. PMID- 1453065 TI - [Endoscopic therapy of early-stage stomach cancer]. PMID- 1453066 TI - [Photodynamic therapy of early-stage stomach cancers]. PMID- 1453067 TI - [Image diagnosis of cardiovascular diseases]. PMID- 1453068 TI - [Aldosteronism and the related diseases]. PMID- 1453069 TI - [Clinical and epidemiological study of cerebrovascular diseases]. PMID- 1453070 TI - [Clinical study on eosinophils]. PMID- 1453071 TI - [Progress on therapy of rheumatoid arthritis]. PMID- 1453072 TI - [Methicillin resistance staphylococcal infections]. PMID- 1453073 TI - [Clinical study on drug-induced nephropathy]. PMID- 1453074 TI - [Physiopathology of systemic lupus erythematosus]. PMID- 1453075 TI - [Clinical study on kidney transplantation]. PMID- 1453076 TI - [Heart lesions in collagen diseases]. PMID- 1453077 TI - [Clinical study on demyelinating diseases]. PMID- 1453079 TI - [Patient's compliance and clinical practice]. PMID- 1453078 TI - [Efficacy and adverse effect of drugs monitored by blood concentration]. PMID- 1453081 TI - [Drug interactions in combination drug therapy]. PMID- 1453080 TI - [Administration of antibiotics for patients with kidney diseases]. PMID- 1453082 TI - Effects of D- and L-isomers of timolol on retinal and choroidal blood flow in ocular hypertensive rabbit eyes. AB - An ocular hypertensive rabbit eye model was used to study the effect of L- and D timolol on retinal and choroidal blood flow. Ocular hypertension was induced artificially by raising the intraocular pressure to 40 mmHg which reduced the ocular blood flow to 1/3 that of the normal blood flow. The effects of L- and D isomers of timolol on the ocular blood flow of ocular hypertensive eyes were then determined using the colored microspheres technique over a range of 0-180 min after eyedrop instillation. It was found that L-timolol produced biphasic action on the blood flow in the iris, ciliary body and choroid by significantly reducing it initially at 30 min, then markedly increasing it later at 90 min and thereafter. Although L-timolol produced a tendency to reduce the blood flow in the retina, it was not statistically significant. At 90 min and thereafter, the blood flow in all ocular tissues was markedly increased by L-timolol. D-timolol did not reduce the blood flow of ocular tissues initially. There was a tendency to increase the blood flow in all ocular tissues from the very beginning by D timolol. The increase of blood flow became significant at 90 min and thereafter, up to 3 hrs. D-timolol was less potent than L-timolol in increasing the blood flow in ocular tissues. PMID- 1453083 TI - Effect of aldose reductase inhibitors on lenticular dulcitol level in galactose fed rats. AB - We have shown that galactose cataract development is delayed or inhibited with the administration of aldose reductase inhibitors (ARIs). Dulcitol forms and accumulates in the lens of rats fed galactose. We undertook investigations to study the effectiveness of ARIs in preventing the formation and accumulation of dulcitol in the lens. Young Sprague Dawley rats were fed Purina Rat Chow with 50% galactose either with or without 15 mg sorbinil, 0.15, 0.5, or 1.0 mg E 0722/day/Kg body weight. At desired intervals following the initiation of diets, the lenses were processed for the determination of galactose and dulcitol levels. The lenticular dulcitol increased significantly in all animals fed galactose reaching a maximum level by approximately 15 days with comparatively lower levels in the groups fed ARIs with galactose; this increase was dose dependent in the groups fed E-0722. There was a subsequent, rapid drop in lenticular dulcitol by 18 days in all dietary groups. Interestingly, a second peak of increased lenticular dulcitol was observed in all groups. The correlation between dulcitol accumulation and cataract development is discussed. PMID- 1453084 TI - Inhibition of ocular inflammation by chalcone derivatives and prednisolone. AB - Posterior uveitis was induced by injection of 10 micrograms endotoxin intravitreally into rat eyes and anterior ocular inflammation was induced by injection of 0.75 mg of lens protein intracamerally into rabbit eyes. Four chalcone derivatives, RVC-556 (2'-hydroxychalcone), RVC-574 (2'-hydroxychalcone hydrazone), RVC-574P (2'-hydroxychalcone phenyl hydrazone) and RVC-588 (4,4' dihydroxy chalcone) were studied along with prednisolone at a dose of 10 mg/kg i.p. t.i.d. for their anti-inflammatory actions. RVC-574 was more active than prednisolone in inhibiting posterior uveitis by 65% and 43%, respectively. RVC 556, RVC-574P, and RVC-588 did not affect the posterior uveitis in rats. On the other hand, anterior ocular inflammation was inhibited by 1% eyedrops of RVC-556, RVC-574P and RVC-588 but not by RVC-574. RVC-556 was more active than; RVC-574P was less active than; and RVC-588 was about equiactive as prednisolone in inhibiting anterior ocular inflammation by 77%, 47%, 69%, and 64%, respectively. PMID- 1453085 TI - Influence of ion pairing salts on the transcorneal permeability of ionized sulfonamides. AB - The effects of cationic ammonium, phosphonium, and arsonium ion pairing salts as well as anionic organic and inorganic salts on the transcorneal permeability of ionized sulfonamide carbonic anhydrase inhibitors have been studied in the excised rabbit cornea. Benzolamide, trichloromethazolamide (TCM), MK-927, and quaternary ammonium sulfonamide (QAS) were examined. The enhancement in the first order rate constants (k(in)) for the first compound in the presence of pairing salts was as much as 15 times the basal rate, with smaller increases seen with the remaining three drugs. Ion pairing salts may represent a means for enhancing the transcorneal permeability of highly ionized drugs. PMID- 1453086 TI - Ocular penetration of topically applied norfloxacin 0.3% in the rabbits and in humans. AB - The kinetics of topically applied norfloxacin 0.3 percent were studied in rabbit and man. All measurements were performed by high-pressure liquid chromatography. Norfloxacin concentrations were investigated five to 120 minutes in rabbit ocular tissues after instillation of a single drop. In normal eyes, after 30 minutes, mean +/- SEM levels were 14.3 +/- 3.7 micrograms/g in cornea, 3.3 +/- 0.7 micrograms/g in conjunctiva, 0.2 +/- 0.1 microgram/g in aqueous humor. After removal of the corneal epithelium concentrations were as follows: 84.2 +/- 15.8 micrograms/g, 7.3 +/- 2.3 micrograms/g, 8.6 +/- 1.9 micrograms/g respectively. Penetration in posterior ocular tissues were rather poor. In human eyes, the intracorneal concentrations were assessed in patients being operated on corneal grafts. After instillation of 5 drops, the concentration in cornea was 15.5 +/- 2.1 micrograms/g. These data show that therapeutic levels of norfloxacin can be achieved in anterior ocular tissues, which may be of help in superficial infections of the eye. PMID- 1453087 TI - Biopharmaceutical explanation for the topical activity of 6-hydroxyethoxy-2 benzothiazolesulfonamide in the rabbit eye. AB - 6-Hydroxyethoxy-2-benzothiazolesulfonamide (compound 1), 6-hydrogen-2 benzothiazolesulfonamide (compound 2) and ethoxzolamide (compound 3) are carbonic anhydrase inhibitors, of which only compound 1 is active in lowering intraocular pressure when administered to the rabbit eye. They were compared for potency by inhibiting carbonic anhydrase I (CAase I) using the pH stat procedure. No differences were detected. Binding affinity and number of binding sites were identical; only a single binding site was operative. 14C-labelled compound 1 was used to measure the presence of an ocular metabolite which ranged from 17 to 57% in cornea, iris/ciliary body and aqueous humor. By maintaining drug solutions on either the corneal or conjunctival/scleral surfaces of the eye of anesthetized rabbits for 120 minutes, steady state concentrations of compounds 1-3 were determined in cornea, aqueous humor and iris/ciliary body. It was concluded that compound 1 penetrated both routes equally well and also accumulated at the active site in considerably higher concentrations than compounds 2 and 3. Compounds 2 and 3 did not accumulate in the iris/ciliary body nor did compound 3 penetrate the conjunctival/scleral route very well, approximately 5-20 fold lower than from the corneal route. PMID- 1453088 TI - Lenticular uptake and distribution of xenobiotics and amino acids. AB - The objective of this study was to explore the relationship between lipophilicity and the lenticular uptake of radiolabeled xenobiotics. The lenticular uptake of amino acids was also investigated. An organ-culture technique was employed and the partitioning of compounds into the rabbit lens was measured for compounds with log octanol/water partition coefficients (log P o/w) ranging from -1 to 7.3. Drug distribution in the lens was expressed as the concentration ratio of that in the lenticular section (capsule/epithelium, cortex, and nucleus) to that in the incubation medium, (C(lens) section/Cm). The drug partitioning into the lens capsule was facile for all of the compounds tested. The drug concentrations in the lens capsule were higher than those in the cortical and nuclear regions. For compounds with low partition coefficients (such as sulfacetamide and cimetidine), an apparent distribution equilibrium was achieved during a 5-hr period. The C(lens)/Cm value of polar compounds, being less than one, did not further increase by prolonging the incubation period. Only compounds with log Po/w values between 3 and 6 had Cnucleus/Cm values exceeding unity. The maximal values of Ccortex/Cm and Cnucleus/Cm, approximately 15 and 4, respectively, for anthracene (log Po/w = 4.5) and diethylstilbestrol (log Po/w = 5.1), were observed in this study. A bell-shaped relationship was observed between the lenticular uptake rate and drug lipophilicity, of which the maximum occurred around log Po/w of 4. These results indicate the existence of a lipophilicity window for favorable drug distribution into the deeper region of the lens. For several lipophilic compounds, such as padimate-O, values of Cnucleus/Cm increased steadily over a 24 hour incubation period. This suggests that the nucleus behaved as a deep compartment for these compounds. L-Cysteine and L-serine were actively taken up by the lens and the lenticular absorption of L-cysteine was concentration dependent with Vmax and Km values of 18.3 mumol/gm/hr and 49.8 mM, respectively. In summary, a relationship between lenticular uptake and drug lipophilicity was demonstrated. The optimal log Po/w value for drug uptake into the lens was between 4 and 5. The slowness of reaching significant drug concentrations in the nucleus necessitates a chronic dosing regimen to deliver therapeutic drug levels inside the lens. PMID- 1453089 TI - ECG of the month. Brain or heart? Intracranial hemorrhage. PMID- 1453090 TI - Eagle's syndrome: the Ochsner experience. AB - Eagle fully described the syndrome that bears his name in 1948. He noted that the typical patient had undergone tonsillectomy in the past. Although reported in the literature, the carotid artery syndrome is frequently overlooked in patients manifesting craniofacial or pharyngeal pain but who have not undergone tonsillectomy. Cases representative of the variety of patients with Eagle's syndrome treated at the Ochsner Clinic Department of Otolaryngology are presented. The diversity of symptoms and its rather uncommon occurrence often make the diagnosis of Eagle's syndrome elusive. The anatomy and embryology of the stylohyoid complex is discussed, as well as the symptoms, differential diagnosis, workup, and treatment of Eagle's syndrome. We hope to refamiliarize the clinician with this condition in order that it be considered in the assessment of patients with craniofacial pain. PMID- 1453091 TI - Preventing the acquisition and further transmission of the HIV virus. PMID- 1453092 TI - TB: new problems for an old menace. PMID- 1453093 TI - AIDS and multidrug-resistant tuberculosis: an epidemic transforms an old disease. AB - Since 1985, tuberculosis case counts in the United States have increased, primarily because of the influence of the HIV epidemic. In addition, during this time outbreaks of multidrug-resistant tuberculosis among patients with AIDS or HIV infection have been reported in New York City and Florida. These outbreaks have occurred in hospitals and prisons and have been characterized by high case fatality rates, disease transmission within the institutions, and high infection rates in health care workers. The increase in tuberculosis rates and the outbreaks have raised concern that multidrug-resistant tuberculosis could become a widespread problem in the United States. Dealing with tuberculosis in the 1990s will require reconsideration of our current methods of tuberculosis prevention, diagnosis, treatment, and control. PMID- 1453094 TI - Current concepts in the management and prevention of tuberculosis in adults. AB - After a steady decline in incidence during most of this century, tuberculosis case rates stabilized in the mid-1980s, and since then have steadily increased. Several factors may have been responsible for the increase, including the influx of immigrants from endemic areas and the appearance of AIDS. This review outlines the current recommendations for treatment of tuberculosis in the otherwise normal patient, then discusses special problems which may affect treatment, including primary drug failure and relapse, pregnancy and lactation, extrapulmonary disease, AIDS, renal failure, and liver disease. The appearance and significance of multiple-drug-resistant tuberculosis (MDRT) in AIDS victims is discussed, and current recommendations for screening patients for the presence of tuberculosis are reviewed. PMID- 1453095 TI - Attacking today's tuberculosis problem: a multifaceted, coordinated effort. AB - Tuberculosis is making a comeback in communities across the nation. Increased rates of the disease, particularly with those having HIV/AIDS, have sounded the alarm that quick and decisive action is needed to halt the spread of TB. Multidrug-resistant TB is becoming a primary concern with public health officials. Specific plans and efforts, instigated by the Centers for Disease Control, have outlined the appropriate steps local public health workers, the medical community, and civic and community organizations should take in order to eliminate TB by the year 2010. With the creation of the Task Force on Drug Resistant Tuberculosis, Louisiana has a vehicle with which to combat its growing TB problem. PMID- 1453096 TI - Tuberculosis in children in 1992. AB - In children, as in adults, tuberculosis is much commoner among minority population groups, in Louisiana particularly among blacks. Since 1986 tuberculosis in some states has increased notably; in Louisiana the increase is only now, in 1992, becoming apparent. Eighteen new cases in children under 20 were reported in 1991. Diagnosis in children still depends largely on history of contact and on the Mantoux tuberculin test. Treatment has changed markedly to a more intensive 6 month course including three or four drugs. Preventive treatment of tuberculin positive children is particularly emphasized because it will play an important role in achieving the stated public health goal of elimination of tuberculosis by the year 2010. With the increasing number of children exposed to tuberculosis, the increasing number of HIV-positive children at risk, and the rising number of multiresistant tubercle bacilli, vaccination with BCG must be considered. PMID- 1453097 TI - New developments in mycobacteria identification: public health laboratory modernization. AB - Clinical laboratory mycobacteriology has traditionally involved long delays for results, primarily due to the slow growth rate of most members of the genus Mycobacterium. Several new methodologies are now available that enable dramatic reductions in turn-around times. These methodologies include the Bactec TB System for isolation and drug susceptibility testing of Mycobacterium tuberculosis, the use of DNA probes, and high performance liquid chromatography (HPLC) for the identification of mycobacterial isolates. The spread of multidrug-resistant tuberculosis has made it imperative that laboratories take advantage of these new methodologies whenever possible. The Mycobacteriology Unit of the Louisiana Office of Public Health's Division of Laboratories has pioneered the use of these methodologies in a public health laboratory setting. Great reductions in turn around times have been achieved and further reductions are expected as the methods are refined and adapted to the needs of a high-volume public health laboratory. PMID- 1453098 TI - More lessons from the remnant kidney. PMID- 1453099 TI - Neonatal neutrophil dysfunction. PMID- 1453100 TI - Ionized calcium in gallbladder bile: new insights into a clear and ever-present danger. PMID- 1453101 TI - The placental transport and use of acyclovir in pregnancy. PMID- 1453102 TI - Aldosterone, cardiac fibrosis, und der freischutz. PMID- 1453103 TI - A sophisticated technique for measurement of nitric oxide: implications for the mechanism of action of nitroglycerin. PMID- 1453104 TI - Biologic markers for cancer: the search for the Holy Grail continues. PMID- 1453105 TI - Medical futility: values, goals, and certainty. PMID- 1453106 TI - The clinical, biochemical, and molecular spectrum of ornithine transcarbamylase deficiency. PMID- 1453107 TI - Supplemented low-protein diets protect the rat kidney without causing undernutrition. AB - Low-protein diets supplemented with keto-analogues and essential amino acid (KA EAA) mixtures or with EAA have been widely used to retard renal deterioration without affecting nutrition. These assumptions have recently been challenged in clinical studies and rest on little or no experimental data. The effects of EAA and KA-EAA supplementations have not been compared. We compared three groups of rats with subtotal nephrectomy that were fed (1) a 16% casein reference (R) diet, (2) a 6% casein plus EAA (A) diet, or (3) a 6% casein plus KA-EAA (K) diet with KA as amino acid salts. The three diets had the same energy and mineral contents, and they induced comparable growth. The two supplements had the same nitrogen content. The only difference found until month 3 was higher proteinuria and plasma urea levels in group R rats. Renal biopsies performed at month 3 showed more severe glomerular sclerosis and tubular changes in R rats than in A and K rats. From months 3 through 7, R rats developed higher plasma creatinine levels than did A and K rats (final median values: 167, 106, and 83 mumol/L; p < 0.04), had more proteinuria (232, 56, and 84 mg/day), and showed greater mortality rates. At the time the rats were killed, 2 R, 6 A, and 5 K rats had survived while receiving the diets. Examination of the remnant kidneys, regardless of time of death, showed that renal lesions were significantly worse in R than in A and K rats, with sclerosis affecting more than 50% of the glomeruli in 7 of 13 R, 4 of 14 A, and 4 of 15 K rats, and less than 25% glomeruli in 2 of 13 R, 10 of 14 A, and 10 of 15 K rats (A and K vs R: p < 0.03). In conclusion, restriction of nonessential amino acids compensated by EAA or by KA-EAA mixtures retards renal damage without affecting growth, but no real benefit of KA or EAA has been observed. PMID- 1453108 TI - Effects of angiotensin-converting enzyme inhibition in diabetic rats with reduced renal function. AB - To test the effect of converting enzyme inhibition (CEI) on diabetes, with or without renal insufficiency, we studied streptozotocin-induced diabetic rats, with or without reduced renal mass, which were treated with insulin in sufficient amounts to maintain glucose values in the mild to moderately hyperglycemic range. We found that diabetes increased glomerular filtration rate (GFR) (inulin clearance, 2.3 +/- 0.5 ml/min vs 1.9 +/- 0.1 ml/min; p < 0.05) and blood pressure (137 +/- 15 mm Hg vs 116 +/- 6 mm Hg; p < 0.05) but did not increase plasma atrial natriuretic peptide (ANP) values, when compared with control rats (72 +/- 38 vs 68 +/- 24 pg/ml). CEI decreased GFR and blood pressure to control values. In rats with diabetes and concomitantly reduced renal mass, hypertension, elevated ANP values, proteinuria, and glomerulosclerosis were prominent features. CEI was associated with reduced blood pressure (172 +/- 17 mm Hg vs 138 +/- 15 mm Hg; p < 0.05), without a concomitant decrease in GFR (1.1 +/- 0.1 ml/min vs 1.1 +/- 0.1 ml/min). Further, CEI reduced the elevated ANP values (140 +/- 34 pg/ml vs 66 +/- 19 pg/ml; p < 0.05) to those of control rats. CEI reduced proteinuria by 50% and ameliorated the histopathologic changes. In separate experiments, rats with 5/6th nephrectomy and hypertension but without diabetes were also found to have elevated ANP levels that decreased to control values with CEI. The data speak for a renal protective effect of angiotensin I-converting enzyme inhibition in this model but do not support a specific role for ANP in the model of diabetes with concomitantly reduced renal mass. PMID- 1453109 TI - Calcium in human gallbladder bile. AB - Biliary calcium is believed to be of great importance in gallstone pathogenesis. These studies were therefore performed to determine if quantitative and/or qualitative differences in calcium are present in gallbladder bile from patients with and without gallstones. Bile was obtained by direct gallbladder aspiration from 68 obese patients undergoing elective gastric bypass surgery. Forty-five patients had no evidence of gallstones or sludge, 18 had cholesterol gallstones, and five had black pigment stones. Gallbladder bile was also obtained from 27 nonobese patients undergoing elective cholecystectomy (19 cholesterol; eight black pigment gallstones). For all patients, total calcium ranged from 1.50 to 16.44 mmol/L (mean: 6.05 +/- 0.31 mmol/L); free Ca++ ion ranged from 0.53 to 2.83 mmol/L (mean: 1.28 +/- 0.05 mmol/L). Considerable overlap was observed between obese and nonobese subjects and between patients with and without gallstones. For all patient groups, calcium, Ca++, and bound calcium increased linearly with increasing concentrations of bile salt. No significant differences in the slopes of these relationships were observed with obesity or gallstones. In contrast, free Ca++ ion was greater in gallbladder bile from gallstone patient groups throughout the entire range of bile salt. We hypothesize that this observed increase in Ca++ resulted from increased Gibbs-Donnan forces and excess gallbladder mucin present within the gallbladder bile of patients with gallstones. PMID- 1453110 TI - Acyclovir transport by the human placenta. AB - Genital Herpes simplex infection is noted increasingly in women of childbearing age and in neonates. Concern about transmission of herpes to the newborn has led to cesarean delivery of many pregnant women with a history of genital herpes. Severe herpes hepatitis has also been noted in pregnancy. Acyclovir is the drug of choice for this infectious organism. Because there are no data on the mechanism(s) of transport of this drug by the human placenta, this study addressed this issue. We used normal term human placentas. For study of overall placental transport of acyclovir, we used the single, isolated perfused cotyledon technique. For assessment of initial acyclovir uptake, we used microvesicles prepared from the maternal-facing syncytiotrophoblast. Overall transfer of acyclovir at therapeutic concentrations from maternal to fetal compartment was at a rate of about 30% that of a freely diffusible marker, antipyrine. The overall transport was not saturable, was not inhibited by 50-fold adenine concentration, and did not proceed against a concentration gradient. There was no placental metabolism of the drug. Fetal-to-maternal transfer of acyclovir was at a similar rate. In maternal-facing microvesicles net uptake of acyclovir was not saturable, but was temperature dependent and was inhibited by high concentrations of adenine and ganciclovir, but not by nucleosides (adenosine, cytidine, cytosine). These data are most consistent with a carrier-dependent, nucleobase-type uptake of the drug, but passive overall net transfer of acyclovir, dependent on its solubility characteristics. PMID- 1453111 TI - Mineralocorticoid excess, dietary sodium, and myocardial fibrosis. AB - Unlike the non-renin-dependent hypertension associated with infrarenal aorta banding, an abnormal accumulation of fibrillar collagen occurs within the adventitia of intramural coronary arteries and neighboring interstitial space of the left and right ventricles in arterial hypertension associated with primary or secondary hyperaldosteronism. Based on these findings it was suggested that this interstitial and perivascular fibrosis was mediated by mineralocorticoid excess (i.e., elevated plasma aldosterone relative to dietary sodium) and not ventricular loading. To further address the importance of mineralocorticoid excess, we examined the fibrous tissue response after 8 weeks in the following uninephrectomized rat groups receiving a high-sodium diet: D-aldosterone (ALDO) infusion (0.75 micrograms/hr sc, n = 16); deoxycorticosterone acetate (DOCA) administration (100 mg/kg/wk sc, n = 8); and administration of a mineralocorticoid-like substance, glycyrrhizic acid (GA; 1 gm kg/wk sc, n = 8). Compared with ALDO infusion and sodium deprivation (n = 9), untreated controls (n = 14), and uninephrectomized rats with high dietary sodium and no mineralocorticoid administration (n = 15), we found (1) hypertension and left ventricular hypertrophy with all forms of mineralocorticoid excess; (2) a rise in collagen volume fraction with ALDO, and an increase in perivascular collagen with DOCA; and (3) no observance of myocardial fibrosis with GA or experimental controls, including ALDO infusion and sodium deprivation. Thus, in the presence of enhanced sodium intake, chronic administration of ALDO or DOCA are associated with collagen accumulation in the myocardium, whereas with the mineralocorticoid like compound GA, myocardial fibrosis was not seen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453112 TI - Endogenous urinary 3-hydroxyproline has 96% specificity and 44% sensitivity for cancer screening. AB - A method for determining the endogenous urinary excretion levels of both 3 hydroxyproline and 4-hydroxyproline that may be useful for cancer screening of the general population and at the workplace is evaluated in this report. The excretion levels of 3-hydroxyproline and 4-hydroxproline were estimated in 97 patients with cancer and in 99 patients with various nonmalignant diseases and were compared with those of 211 healthy persons. Measurable 3-hydroxyproline peaks (by amino acid autoanalyzer) were absent from 93 samples from 211 healthy persons (44%), 50 of 99 patients with nonmalignant disease (50%), and 10 of 96 patients with cancer (10%). The levels of both 3-hydroxyproline and 4 hydroxyproline in cancer patients were significantly higher than those in healthy persons (p < 0.001 and p < 0.01, respectively) and those in patients with nonmalignant diseases (p < 0.05 and p < 0.01, respectively). Cancer patients were classified into three groups according to grade of cancer growth and invasion. The sensitivity of 3-hydroxyproline was 44% and higher than that of 4 hydroxyproline for the detection of stage II cancers (no distant metastasis); the sensitivities of both hydroxyprolines for the detection of stage I (very early cancer) were low. The specificity of these assays for healthy persons and patients with nonmalignant disease was 96% and 92% for 3-hydroxyproline, and 97% and 79% for 4-hydroxyproline, respectively. Urinary 3-hydroxyproline level should be further investigated as a cancer screening method for healthy persons in the community or the workplace, but appears unlikely to detect many cancers in the earliest stages. PMID- 1453113 TI - Reduced membrane fluidity and increased glycation of membrane proteins of platelets from diabetic subjects are not associated with increased platelet adherence to glycated collagen. AB - Platelets could contribute to vascular disease in diabetes through enhanced adherence to collagen exposed in injured vessels. Increased platelet adherence to collagen in diabetes could result from an alteration in platelets and/or platelet hypersensitivity to collagen that has been glycated to a greater extent. In this study, the adherence of platelets from diabetic or control subjects to glycated or nonglycated collagen coated onto glass surfaces was examined. Membrane fluidity of platelets was also determined, since decreased membrane fluidity associated with increased glycation of membrane proteins of platelets from diabetic subjects was shown in a previous study, and decreases in membrane fluidity have been shown by others to increase platelet adhesion. Thirteen diabetic subjects were compared with 13 age-and sex-matched control subjects. Collagen was glycated (9.7 nmol glucose/mg protein) by preincubation for 12 days in glucose-rich medium (500 mmol/L). A control solution of collagen incubated without glucose for the same time had 3.3 nmol glucose/mg protein. There were no differences in the adherence of platelets from diabetic and control subjects to nonglycated and glycated collagen-coated glass. The mean steady-state fluorescence polarization value (0.187 +/- 0.002) in 1.6-diphenyl-1,3,5 hexatriene-labeled platelets from diabetic subjects was significantly greater than in platelets from control subjects (0.174 +/- 0.002, p < 0.002); thus membrane fluidity in platelets from the group of diabetic subjects was decreased. The extent of glycation of membrane proteins from diabetic subjects (25.4 +/- 0.5 nmol glucose/mg protein) was significantly greater than from control subjects (20.2 +/- 0.4 nmol glucose/mg protein, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453114 TI - Mechanisms of glucagon-induced renal vasodilation: role of prostaglandins and endothelium-derived relaxing factor. AB - The mechanisms underlying the renal hemodynamic responses (vasodilation and hyperfiltration) to an amino acid or protein load are currently unknown and are relevant to understanding the effect of dietary protein on the progression of chronic renal failure. Glucagon (GLC) has been suggested to be important in these renal hemodynamic responses, although the mechanism is again unclear. Thus we investigated potential mediators of the renal hemodynamic response to GLC in the anesthetized rat, including prostanoids and endothelium-derived relaxing factor (EDRF). The effects of glucagon alone and after pretreatment were tested as follows: (1) after baseline renal hemodynamic measurements done with clearance techniques, rats were given GLC alone (n = 5; 200 ng/min IV continuous infusion); (2) glucagon was given after pretreatment with the EDRF synthesis inhibitor nitro arginine-methyl-ester (NAME; n = 6; 125 micrograms/kg/min intrarenal artery by continuous infusion); (3) glucagon was given after pretreatment with indomethacin (INDO; n = 6; 5 mg/kg IV bolus). Repeat clearances demonstrated that GLC infusion increased glomerular filtration rate (GFR; basal vs GLC, 0.87 +/- 0.04 ml/min vs 1.14 +/- 0.09 ml/min, p < 0.05); renal plasma flow (RPF; 4.10 +/- 0.18 ml/min vs 5.56 +/- 0.32 ml/min, p < 0.05) and decreased renal vascular resistance (RVR; 15.82 +/- 1.17 mm Hg/[ml/min] vs 10.72 +/- 0.65 mm Hg/[ml/min], p < 0.05). Intrarenal N-nitro-L-arginine-methyl-ester (NAME) infusion significantly reduced basal GFR (-20% +/- 8%, p < 0.05) and RPF (-43% +/- 2%, p < 0.05), while increasing RVR (+108% +/- 9%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453115 TI - The pituitary-gonadal axis in experimental nephrotic syndrome in male rats. AB - Basal and luteinizing releasing hormone-stimulated gonadotropin secretion were studied in male rats made nephrotic with puromycin, and in pair-fed and normal control animals. In addition, plasma concentrations of testosterone, androstenedione, estradiol, and estrone were measured in the three groups of animals. Urinary testosterone concentrations were also measured in the three experimental groups. The data showed that basal luteinizing hormone concentration was significantly elevated in the nephrotic group compared with the pair-fed and normal control groups. Gonadotropin response to luteinizing releasing hormone stimulation was not significantly different in the three groups, suggesting an intact hypothalamic-pituitary axis in nephrotic syndrome. Urinary testosterone concentration in the nephrotic animals was significantly higher than in the pair fed and normal control groups. Plasma testosterone, androstenedione, estradiol, and estrone concentrations were significantly lower in the nephrotic and pair-fed animals than in the normal control animals, indicating possibly impaired gonadal steroidogenesis in these two groups that may be related to the catabolic state of the animals. It thus appears that urinary loss of protein-bound (sex hormone binding globulin-bound) testosterone in the nephrotic syndrome leads to increased basal secretion of luteinizing hormone, presumably as a result of increased luteinizing releasing hormone secretion. This occurs to compensate for the abnormal urinary testosterone loss and is an attempt to restore plasma testosterone concentrations to normal. The higher basal plasma luteinizing hormone concentration in the nephrotic group supports this conclusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453116 TI - Amiodarone-induced endothelial injury is associated with phospholipase C-mediated hydrolysis of membrane phospholipids. AB - Phospholipids accumulate within the lysosomes of various cells from individuals taking amiodarone. Studies on cultured cells suggest that inhibition of lysosomal phospholipase A1 and phospholipase A2 by amiodarone may be responsible for this derangement in phospholipid metabolism. Inhibition of lysosomal phospholipases by amiodarone has been suggested as a mechanism of its toxicity, but this relationship has not been clearly established. To examine this question, membrane phospholipids of cultured bovine pulmonary artery endothelial cells (BPAEC) were labeled with 14C-stearic acid, 3H-arachidonic acid, 14C-choline, or 14C ethanolamine. Radiolabeled BPAEC were then exposed to various concentrations of amiodarone, and endothelial phospholipase activity was measured by isolating and quantifying various phospholipase products. These findings were compared to a standard indicator of endothelial cytotoxicity using 51Cr release. Six-hour exposures to 5 to 20 micrograms/ml amiodarone produced no BPAEC toxicity and were accompanied by some evidence of decreased phospholipid hydrolysis. At concentrations above 20 micrograms/ml, amiodarone caused significant BPAEC toxicity as indicated by 51Cr release, and this was closely associated with the liberation of substantial amounts of 3H-arachidonic acid and 14C-stearic acid from phosphatidylcholine and phosphatidylethanolamine. In BPAEC labeled with 14C choline and 14C-ethanolamine, cytotoxic doses of amiodarone caused accumulations of 14C-phosphocholine and phosphorylethanolamine, expected products of phospholipase C, but without increases in phospholipase A products. We conclude that exposure of BPAEC to toxic concentrations of amiodarone is associated with extensive hydrolysis of phosphatidylcholine and lysophosphatidylethanolamine via a phospholipase C-specific mechanism, and suggest that this may be a mechanism in the pathogenesis of amiodarone toxicity. PMID- 1453117 TI - The effects of extracellular calcium on prairie dog gallbladder ion transport. AB - Recent studies suggest that experimentally induced gallstone formation is associated with altered gallbladder absorptive function. Moreover, elevated biliary levels of calcium have been implicated in the pathogenesis of cholesterol gallstones. Nonetheless, the relationship between gallbladder ion transport and biliary calcium remains obscure. We tested the hypothesis that extracellular calcium modulates gallbladder ion transport. Prairie dog gallbladders were mounted in an Ussing chamber, and short-circuit current (Isc), transepithelial potential difference (Vms), and tissue resistance (Rt) were measured. Tissues were randomly exposed to physiologic salt solutions containing the following concentrations of calcium: 0.01, 1.3, 5, and 10 mmol/L. Exposure of gallbladder epithelium to increasing calcium concentrations resulted in concomitant increases in Isc and Vms (p < 0.001), without altering Rt. Regression analysis demonstrated a curvilinear correlation between calcium and Isc (Y = 167 + 22.5x - 1.4 x 26; p < 0.001). We conclude that extracellular calcium may be a modulator of gallbladder ion transport. PMID- 1453118 TI - Laminin B1 is preferentially expressed in the cortex of rat kidney and is not affected by cyclosporine administration. AB - Cyclosporine has proven beneficial as an immunosuppressive agent for organ rejection in kidney transplants as well as in heart and liver transplants. Cyclosporine administration, however, is associated with certain adverse effects, one of the most important being chronic nephrotoxicity characterized by focal cortical scarring. Recent experimental data show involvement of type I and possibly type IV collagens in this process. Because laminin represents another potential extracellular matrix target, we examined the effects of cyclosporine administration in rats on the expression of laminin at the messenger ribonucleic acid (mRNA) and protein levels. In untreated normal rats, laminin B1 mRNA is preferentially expressed in the renal cortices, as demonstrated by northern blots. Daily administration of cyclosporine leads to focal cortical interstitial fibrosis and tubular atrophy by 4 weeks with, as shown previously, elevated procollagen alpha-1 (type I) mRNA levels at 1 and 4 weeks. In contrast, the amounts of message for laminin B1 remain identical after 1 week and 4 weeks of cyclosporine administration, despite the development of fibrosis at 4 weeks. Similar results were obtained with antilaminin antibody. We conclude that laminin is abundant in renal cortical tissues as compared with its medullary contents and is not altered in the process of renal cortical fibrosis induced by cyclosporine. PMID- 1453119 TI - 183rd meeting of the Society for Endocrinology. London, 25-27 November 1992. Abstracts. PMID- 1453120 TI - Quality assurance in internal medicine. PMID- 1453121 TI - First-line pharmacological treatment of hypertension. PMID- 1453122 TI - Metabolic disturbances in hypertension: results from the population study 'men born in 1913'. AB - A clustering of metabolic disturbances has been indicated in hypertension. The distribution of such factors was assessed among hypertensives and normotensives in a general population sample of 644 men aged 67 years. Fasting serum insulin, glucose and triglyceride levels were measured. In this study hypertension was defined as DBP > or = 95 mmHg or present use of antihypertensives. Impaired glucose tolerance (IGT) or diabetes mellitus, hyperinsulinaemia (> or = 20 mU l 1) and hypertriglyceridaemia (> or = 2.3 mmol l-1) were defined as metabolic disturbances. When all these disturbances were present simultaneously a complete 'metabolic syndrome' was considered to be present. Hypertension was found in 185 (29%) men, IGT in 15%, diabetes mellitus in 11%, hyperinsulinaemia in 18% and hypertriglyceridaemia in 19%. Among hypertensives, 11 (6%) men had a 'metabolic syndrome', compared to 12 (3%) men in the normotensive group (P = 0.039). At least one metabolic disturbance was present in 109 (59%) of the hypertensive men, and in 173 (38%) of the normotensive men (P < 0.001). The prevalence rates of metabolic disturbances did not differ significantly between lean (BMI < 26 kg m 2) and obese (BMI > or = 26 kg m-2) hypertensives. Only hypertriglyceridaemia was more frequent in obese than in lean hypertensives (20% vs. 37%, P = 0.015). The 'metabolic syndrome' was found in 6% of all hypertensives, which was twice as common as in the normotensive population. The 'metabolic syndrome' was uncommon in both lean and obese hypertensives (5% vs. 7%, NS). These findings indicate that hypertension and metabolic disturbances may have a common underlying cause, at least in some individuals. PMID- 1453123 TI - Association between high levels of growth factors in plasma and progression of coronary atherosclerosis. AB - Although intimal proliferation of smooth muscle cells (SMC) is recognized as one of the key mechanisms in the development of atherosclerosis, our knowledge of the role of circulating growth factors for SMC in this process is limited. In the present study the plasma levels of platelet-derived growth factor (PDGF), beta thromboglobulin (beta-TG), platelet factor 4 (PF 4) and total growth factor activity were determined in a group of 30 young postinfarction patients who had participated in an angiographic study of mechanisms associated with progression of coronary atherosclerosis. Significant correlations were found between the total growth factor activity in plasma and progression (r = 0.42, P < 0.05), as well as severity (r = 0.52, P < 0.01), of global coronary atherosclerosis. Attempts to identify the nature of the total growth factor activity indicated that less than 20% could be attributed to PDGF, the major serum mitogen for SMC. PDGF levels determined by radioimmunoassay were not related to progression or severity of global coronary atherosclerosis, but showed a significant association with the number and severity of distinct stenoses (r = 0.40, P < 0.05). Due to the retrospective design of this study, it is not possible to conclude whether there is a causal relationship between circulating growth factors and development of coronary atherosclerosis. PMID- 1453124 TI - Occurrence of species of low-density lipoprotein with defective clearance in patients with primary moderate hypercholesterolaemia. AB - Recent studies have shown that one cause of primary moderate hypercholesterolaemia is familial defective apolipoprotein B-100 (FDB), a condition in which a mutation in apolipoprotein B-100 (apo B-100) causes low density lipoproteins (LDL) to bind poorly to LDL receptors. One specific mutation, a glutamine-for-arginine transformation at position 3500 of apo B-100, has been reported to produce FDB. However, other mutations in apo B-100 might also cause FDB. The present study was designed to determine whether some patients with hypercholesterolaemia, who do not have the 3500 defect, may have a slowly cleared subfraction of LDL compatible with other forms of FDB. It was postulated that slowly removed LDL should accumulate excess cholesterol ester and hence be less dense than normal LDL. If so, in patients who are heterozygous for FDB, two forms of LDL might be separable by ultracentrifugation. To test this hypothesis, less-dense (d = 1.030 g ml-1) and more-dense (d = 1.040 g ml-1) subfractions of LDL were isolated from a patient with proven FDB (3500 mutation); the two forms of LDL were labelled with different isotopes of radioiodine and re-injected into the patient. The less-dense form was removed much more slowly (0.285 pools day-1) than more-dense LDL (0.570 pools day-1). This finding appeared to confirm the validity of the approach. The same procedure was then applied to 18 other patients having elevated LDL cholesterol but not the 3500 mutation. In 13 patients, the two forms of LDL were removed at essentially identical rates, suggesting that they did not have an abnormal form of LDL. In the other five, less-dense LDL were removed at a significantly slower rate than more-dense LDL; this finding suggests that a significant portion of patients with moderate hypercholesterolaemia have an abnormal LDL species, which is not the 3500 mutation, but delays clearance of LDL from the circulation. PMID- 1453125 TI - The relationship between the transfer factor obtained at rest, and arterial oxygen tension during exercise, in patients with miscellaneous pulmonary diseases. AB - Forty-one consecutive patients with the symptom 'exertional dyspnoea' were referred to the Department of Clinical Physiology for evaluation. Pulmonary fibrosis and chronic obstructive pulmonary disease were the most common diagnoses but other diagnoses were also represented. Some patients had no clinical diagnosis or radiological signs. All patients underwent exercise testing with sampling of arterial blood for blood gas analysis and pulmonary function testing including measurement of the transfer factor (carbon monoxide diffusing capacity) at rest. Independent of spirometric findings and diagnosis a significant correlation (r = 0.80, P < 0.001) was shown to exist between the transfer factor measured at rest and the arterial oxygen tension at maximal exercise level. We recommend measurement of the transfer factor as a screening test for exertional hypoxaemia and suggest that exercise blood gas analysis only seems necessary in patients with a transfer factor between 55% and 80% of the predicted value. PMID- 1453126 TI - Increasing parathyroid hormone concentrations in untreated primary hyperparathyroidism. AB - Twenty-four patients with mild to moderate primary hyperparathyroidism were followed for an average of 2.45 years with serial determinations of serum ionized calcium and intact parathyroid hormone (PTH). For the entire group serum ionized calcium remained stable, whereas serum PTH increased significantly. Eleven patients (group 1) demonstrated a significant increase in PTH with time. The remaining 13 patients formed group 2. Comparison of the changes (%) in each subgroup showed a small but significant increase in serum ionized calcium of 2.6% with time in group 1, while serum PTH increased by 78%. In group 2 serum ionized calcium remained stable whereas PTH increased modestly by 22%. Serum concentrations of creatinine were stable throughout the follow-up period in both groups. Despite the greater precision of serum ionized calcium, measurements of intact PTH are evidently more sensitive than measurements of serum ionized calcium for the detection of progression in primary hyperparathyroidism. PMID- 1453127 TI - Diagnosis of acute symptomatic aortic aneurysm--ultrasonography an important tool. AB - Symptomatic aortic aneurysm is an extremely acute condition with manifest or threatening aortic rupture. The mortality is high and urgent surgery is essential and often life-saving. A correct diagnosis needs to be made without delay, a fact which places great demands on the doctor--often not a surgeon--who is first consulted by the patient. The differential diagnosis and emergency management are discussed here against the background of the course of events in four patients with aortic aneurysm who were referred erroneously for admission to a coronary intensive care unit during a 12-month period. Two of the patients died. The ultrasonographic findings were decisive for the outcome in the two surviving patients and yielded a rapid diagnosis in one further case. Ultrasonography is recommended as the method of first choice for verifying or excluding this condition when it is suspected on clinical grounds. PMID- 1453128 TI - Survival in 91 adults with acute myelogenous leukaemia treated with 1-6 intensive courses of chemotherapy. AB - Ninety-one patients with acute myelogenous leukaemia (AML) aged 17-59 years were treated with a chemotherapy programme which could be completed within 30 weeks for patients who achieved complete remission (CR). Four courses included daunorubicin, cytarabine and thioguanine, while two courses included amsacrine, etoposide and cytarabine. Sixty-five patients obtained CR (71%), more often in patients below (82%) than above (60%) 40 years of age (P = 0.03). Five patients underwent allogenic bone-marrow transplantation, and one patient received an autologous bone-marrow transplant after relapse. Five patients developed central nervous system leukaemia. The overall actuarial 3- and 5-year survival was 29% and 21%, respectively; for patients who obtained CR the corresponding survival rates were 40% and 30%, respectively. Patients below 40 years of age appeared to fare better (5-year survival 26%) than older patients (5-year survival 16%). The estimated disease-free survival rate was 26% at 3 years and 22% at 5 years. The main advantage of this regimen is that results compare favourably with those obtained with other regimens were achieved, without exposing patients to long periods of maintenance therapy. PMID- 1453129 TI - Immunoreactive interleukin-6 in serum of patients with B-lymphoproliferative diseases. AB - Serum immunoreactive interleukin-6 (ir-IL-6) concentration was measured by radioimmunoassay in nine patients with chronic lymphocytic leukaemia (CLL), 16 patients with multiple myeloma (MM), 12 patients with monoclonal gammapathy of undetermined significance (MGUS), 22 patients with primary Sjogren's syndrome (SS), and in 32 control subjects. Measurable quantities of ir-IL-6 were detected in every sample studied. Patients with MGUS and SS had significantly higher serum ir-IL-6 (mean +/- SD) concentrations (337 +/- 92 ng l-1 and 299 +/- 100 ng l-1, respectively) than controls (92 +/- 77 ng l-1) and patients with CLL and MM (120 +/- 32 ng l-1 and 113 +/- 58 ng l-1, respectively). Longitudinal studies of ir-IL 6 concentration in a few patients with MM showed a decrease before remission and an increase prior to relapse, but no consistent pattern was detected. In conclusion, we found that serum ir-IL-6 levels are higher in patients with benign hypergammaglobulinaemic states than in patients with malignant neoplastic B-cell disorders. PMID- 1453130 TI - Haematologic effects of granulocyte-macrophage colony stimulating factor in a patient with thiamazole-induced agranulocytosis. AB - A 61-year-old female patient, treated for hyperthyroidism with thiamazole, developed a severe maturation arrest in the granulocytic lineage and a total agranulocytosis. Subcutaneous GM-CSF was started immediately and given for 6 days. Bone marrow samples were taken before GM-CSF therapy and on days 3 and 8. An increased number of colonies per 10(5) bone marrow cells documented before institution of GM-CSF treatment was followed by a gradual decline to normal values. An increase of granulocyte count to > 0.5 x 10(9) l-1 was recorded on the 4th day of treatment and was preceded by an increase in the number of immature granulocyte precursors in the bone marrow on day 3. The patient was discharged on day 8 and experienced no adverse effects of GM-CSF treatment. Haematopoietic growth factor therapy has a place in the management of patients with drug induced neutropenia/agranulocytosis, which should be further delineated by prospective studies. PMID- 1453131 TI - The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I. AB - Insulin-like growth factor I (IGF-I) is an important anabolic factor for osteoblasts in vitro. Low plasma levels of IGF-I have been observed in young men with osteoporosis. In the present study, we have studied bone mineral density (BMD) and the circulating levels of IGF-I and growth hormone (GH) in adults with acquired GH deficiency. BMD was determined by dual-energy x-ray absorptiometry in 17 men and 12 women (age 27-54 years). Spinal BMD was positively correlated with the plasma levels of IGF-I (r = 0.43, P = 0.019), with the median of GH values obtained by repeated sampling at night (r = 0.43, P = 0.0019), and with the peak of GH values during GHRH provocation test (r = 0.49, P = 0.039). The total BMD was positively related to plasma IGF-I and median of GH values, but not to peak GH by GHRH provocation. In a multiple regression analysis model, IGF-I, peak GH by GHRH provocation test and duration of GH deficiency explained 49% of the variation in spinal BMD. As compared to healthy controls, total, but not spinal, bone mass was lower in men with GH deficiency, but no clinical symptoms of osteoporosis were observed. The positive relationships between BMD and circulating IGF-I and other indices of GH secretion suggest that IGF-I has an endocrine effect on bone mass. PMID- 1453132 TI - Testosterone/epitestosterone ratio in urine: a possible diagnostic tool in the disclosure of exogenous testosterone administration. AB - A 37-year-old woman presented with a history of secondary amenorrhoea and hirsutism for 4 years. She had elevated serum levels of testosterone and dihydrotestosterone, and decreased serum levels of sex hormone binding globulin and oestradiol. Almost daily use of a testosterone-containing ointment in the vulvar region for 6 years was disclosed as the cause of the hyperandrogenism. Serum testosterone, testosterone excretion rate in urine and testosterone/epitestosterone ratio in urine were determined at fixed intervals 24 h before and 48 h after application of the testosterone-containing ointment. There was a rapid increase in serum testosterone, with a peak level after 4-6 h. The testosterone excretion rate and the testosterone/epitestosterone ratio in urine peaked after 2-4 h. After 48 h the serum testosterone level was still about twice the basal value. The testosterone/epitestosterone level was over the 'doping limit' of 6 for 28 h. We conclude that determination of the testosterone/epitestosterone ratio in urine would have disclosed exogenous testosterone administration in this patient. We recommend this test for patients in whom exogenous testosterone administration is suspected. PMID- 1453133 TI - Two UV-induced episodes of myelitis in a patient with systemic lupus erythematosus. AB - Two flares of acute myelitis were observed in a 31-year-old woman with previously known mild SLE. The two myelitic episodes both occurred within 1 week after intense sun exposure, and for this reason photobiological induction of the manifestation is considered likely. The diagnostic utility of MRI in the acute situation and the possible influence of sex-steroids on SLE manifestations are also illustrated by this case. PMID- 1453134 TI - On estimating processing variance: commentary and reanalysis of Kail's "Developmental functions for speeds of cognitive processes". AB - A recent paper by Kail (1988) in this journal appears to contain a significant error in the data analysis. The "goodness-of-fit" coefficients reported which suggest that overall about 94% of the variance can be accounted for by the model seem to be a substantial overestimation as a result of inappropriate procedures for statistical modeling. Using the data made available to us by Kail, we have reanalyzed these results. The corrected values range from 0.9 to 92.1% for the individual tasks with an overall average between 40 and 60%. We suggest that the support for the original conclusions is considerably weaker than reported. PMID- 1453135 TI - Evidence for global developmental change is intact. AB - In this article, I argue that most of the claims made by Morrison, Morrison, and Keating (1992) do not undermine the key results of the Kail (1988) study and that, contrary to their claims, the evidence still provides support for the original conclusion that a global mechanism is implicated in age-related change in speed of processing. PMID- 1453136 TI - Covert orienting to central visual cues and sport practice relations in the development of visual attention. AB - This study examines the development of controlled covert orienting of visual attention, according to the age and the level of performance of tennis players. Practicers and nonpracticers age 13, 16, and 25 participated in a covert orienting task. On each trial, subjects responded to a target which appeared in one of four locations arrayed horizontally across the display. Three central cues were used: neutral, the cue did not specify in which location the target would appear; valid, the target was present in the cued location on 80% of the trials; invalid, the target was present in one of the uncued locations on the remaining 20% of the trials. The results showed that (1) practicers were not faster than nonpracticers in processing the signals, (2) observers of all ages oriented attention voluntarily to the cued locations, (3) central cues had a smaller effect on older and practiced subjects, and (4) developmental and sport practice factors had similar effects on orienting efficiency. The implications of these findings for theories of attentional development are discussed. PMID- 1453137 TI - Operativity and the superordinate categorization of artifacts. AB - Relations between typical and atypical exemplars of superordinate categories are low in figurative similarity, i.e., similarity based in appearance or in spatial/temporal context. Operativity, as an emergent competence to overcome figurative cues and establish nonfigurative relations, might be expected to contribute to superordinate categorization. The present study assessed the relative consistency of age-equivalent preoperational and concrete-operational groups of first graders across two categorization tasks employing color drawings of exemplars of superordinate artifact categories. Concrete-operational subjects categorized two exemplars together on a Sample-Match Task if they had previously included both exemplars under the same category on a Category-Membership Task. In addition to membership in the same category, preoperational subjects required that both exemplars be typical before categorizing them together on the Sample Match Task. The cognitive levels did not differ in their category membership decisions. Results are discussed in terms of both utilization and acquisition of superordinate knowledge. PMID- 1453138 TI - The role of attention in children's time perception. AB - This study tested the role of attention in 7- to 9-year-old children's time estimation. Based on an attentional model of time estimation, it was hypothesized that prospective estimates of short intervals are a function of the degree to which a child is occupied with the passage of time and is focusing his or her attention on estimating the exposure time of a stimulus. Two experiments with two different manipulations on attentional focus were conducted. Eighty children were exposed to two types of light bulbs, one a big bulb kindled with high intensity and the other a small one kindled with low intensity. The light bulbs were kindled for different intervals ranging from 3 to 10 s. In both experiments children estimated the lighting time of the bulbs in each condition by a reproduction method. In the first experiment prospective time estimates were found to be significantly longer than retrospective ones. In the second experiment children gave shorter time estimates when their attention was attracted away from the time estimation task than when it was not. In both experiments the attentional hypothesis was supported. In addition, support for the "more is more" hypothesis was obtained. Implications for understanding children's time perception processes are discussed. PMID- 1453139 TI - Counting knowledge and skill in cognitive addition: a comparison of normal and mathematically disabled children. AB - The relationship between counting knowledge and computational skills (i.e., skill at counting to solve addition problems) was assessed for groups of first-grade normal and mathematically disabled (MD) children. Twenty-four normal and 13 MD children were administered a series of counting tasks and solved 40 computer administered addition problems. For the addition task, problem-solving strategies were recorded on a trial-by-trial basis. Performance on the counting tasks suggested that the MD children were developmentally delayed in the understanding of essential and unessential features of counting and were relatively unskilled in the detection of certain forms of counting error. On the addition task, the MD children committed many more computational errors and tended to use developmentally immature counting procedures. The immature counting knowledge of the MD children, combined with their relatively poor skills at detecting counting errors, appeared to underlie their poor computational skills on the addition task. Suggestions for future research are presented. PMID- 1453140 TI - Clarifying the role of shape in children's taxonomic assumption. AB - When asked to find a new referent of a novel label children tend to ignore thematic relations (e.g., the relation between a spider and its web) and focus instead on taxonomic relations (e.g., the relation between a spider and a snake). The precise nature of children's taxonomic assumption has not been clear, however. One possibility is that the taxonomic assumption reduces to a "similar shape rule": perhaps children tend to select objects of the same taxonomic kind when asked to extend new labels simply because these objects are more similar in shape than objects which are only thematically related. Sixty children between 3 and 5 years of age participated in three studies which examined children's attention to thematic relations, similarity of shape, and taxonomic relations when extending novel object labels. The findings indicated that shape has some primacy in children's expectations about object label reference, yet when shape is not available as a guide, children also take taxonomic kind into consideration when searching for new referents of novel labels. Thus children make use of a relatively rich and somewhat varied set of expectations to guide their inferences about object label reference. PMID- 1453141 TI - "Right decisions, right now". PMID- 1453142 TI - Consultations and referrals. PMID- 1453143 TI - Spirituality. PMID- 1453144 TI - Drug-prescribing questions. PMID- 1453145 TI - Current management of streptococcal pharyngitis. PMID- 1453146 TI - Clarithromycin vs penicillin in the treatment of streptococcal pharyngitis. AB - BACKGROUND: Streptococcal pharyngitis, caused by group A beta-hemolytic streptococci (GABHS), is among the most common infections seen by primary care physicians. Because the illness can result in rheumatic fever, early eradication of infection is important. Penicillin has been the standard treatment for GABHS pharyngitis for over four decades, but reports of bacteriologic failure with this drug in recent years have led to trials of alternative antimicrobials. METHODS: In this investigator-blind, randomized multicenter trial (30 centers), oral clarithromycin, 250 mg twice daily, or oral penicillin VK, 250 mg three times daily, was given to outpatients > or = 12 years old with GABHS pharyngitis as documented by positive cultures for Streptococcus pyogenes and positive rapid immunoassay tests. The clinical and bacteriologic efficacy of clarithromycin was compared with that of penicillin in the 356 evaluable patients. Safety analysis was performed in all patients who had received at least one dose of the study drug (N = 453). RESULTS: Overall, clinical outcomes were comparable in the two groups. However, more clarithromycin-treated patients than penicillin-treated patients had resolution of sore throat (94% vs 86%, P = .014) and disappearance of pharyngeal erythema and exudate (89% vs 82%, P = .05). Bacteriologic cure rates were higher in clarithromycin-treated patients (95% vs 87%, P = .009). No serious adverse events were observed in either group. CONCLUSIONS: This study suggests that clarithromycin twice daily is as effective and as well tolerated as penicillin in the treatment of streptococcal pharyngitis. PMID- 1453147 TI - Patients' attitudes regarding chaperones during physical examinations. AB - BACKGROUND: This study was undertaken to determine the preference of patients concerning the presence of a chaperone during physical examination of the breasts, genitals, rectum, heart and lungs, or abdomen. The study was designed to quantify preference differences between male and female patients and between teenagers and adults, and to determine whether the sex of the examining physician influenced chaperone preference. METHODS: Preference survey data were obtained from 251 female subjects and 201 male subjects over the age of 13 years who visited a family practice center in a midwestern urban community. RESULTS: The majority of patients of either sex and all ages did not care if a chaperone was present. However, substantial proportions of adult women (29%) and female teenagers (46%) preferred that a chaperone be present during a breast, pelvic, or rectal examination by a male physician. Thirty-six percent of adult women and 63% of female teenagers wanted a chaperone present during a first examination of these regions. Adults of both sexes felt the nurse would be the best chaperone, whereas teenagers ranked a parent first and the nurse second. Patients indicated that they felt comfortable asking for a chaperone. CONCLUSIONS: Although most patients have no strong preference, female patients, especially female teenagers, should be given the option of having a chaperone present during an examination of the breasts, pelvis, or rectum by a male physician. PMID- 1453148 TI - Relationship between Pap smear performance and physician ordering a mammogram. AB - BACKGROUND: Although Pap smear screening for cervical cancer in general has been successfully implemented, mammography screening for breast cancer remains relatively underused. Patients having one screening test are more likely to have other screening tests performed. The objective of this study was to determine whether visits by women for Pap smears serve as opportunities for physicians to order a screening mammogram. METHODS: A matched case-control design was used for this retrospective study. Eligible women included those over 50 years of age who had no history of breast cancer or mastectomy and who had made at least one visit to a family practice residency program during the 2-year study period. Cases were randomly selected from women who had mammograms performed. For each case, one control subject who did not have a mammogram was matched by age and number of visits. A chart audit was performed to collect data on the characteristics of these women and whether they completed their screening tests. RESULTS: The adjusted odds ratio (controlling for the patient's age and number of physician visits) for mammogram completion among women who had a Pap smear compared with those who did not was 6.67. This effect persisted after controlling for other confounding factors using logistic regression. CONCLUSIONS: Performing a Pap smear appears to serve as a prompt for the physician to order a screening mammogram. That physicians appear to provide screening tests, particularly Pap smears and mammograms, as a package of services should be considered when future efforts to improve implementation are made. PMID- 1453149 TI - Outpatients' attitudes regarding advance directives. AB - BACKGROUND: Although many bedside ethical dilemmas can be avoided if patients discuss their wishes regarding the use of life-prolonging treatment and aggressiveness of care, many physicians are reluctant to raise this issue with their patients. Physicians may wait for such discussions until a patient is ill or elderly or until the patient raises the issue first. METHODS: Three hundred adult patients visiting their family physician's office were asked to complete a 19-item questionnaire. In addition to providing demographic information, they were asked whether they had discussed their wishes regarding life-prolonging treatments with their physician; what their attitude was toward having these discussions in various situations; whom they wanted to initiate the discussion, and with whom else they had discussed their wishes. RESULTS: Of the respondents who had not previously discussed their wishes with their physician, 68% wanted the physician to initiate the discussion. Only 11% did not want their physician to bring up the subject. A majority of respondents in all age groups thought it was somewhat or very important to discuss this matter both when healthy and when very ill. CONCLUSIONS: Very few patients would be upset if their physician raised the issue of life-prolonging treatment even if he or she did so during an initial patient visit. To avoid problems later, physicians should take an active role by raising these questions early in the patient-physician relationship rather than waiting for the patient to do so. PMID- 1453150 TI - The impact of a patient survey or a physician reminder on the provision of adolescent preventive health care. AB - BACKGROUND: The objective of this study was to determine if the use of a patient survey or a chart stamp could increase the implementation of adolescent preventive health care in a family practice center. METHODS: Subjects were all patients 13 to 18 years old (date of birth 1972 to 1977), who visited the Aultman Family Practice Centers from October 1, 1989, through September 30, 1990 (N = 801 patient visits). Three different 1-month interventions (patient questionnaire, physician stamp, and both patient questionnaire and physician stamp) as well as a 1-month control period were implemented. The effect of the intervention on adolescent preventive health care was measured by review of documentation in the patient's chart. RESULTS: Those charts that indicated that either the questionnaire or stamp had been used showed significantly more documented discussion of issues relating to mood, injury, sexuality, exposure to toxins, and lifestyle (all P < .01). These discussions most commonly took place during a visit for a physical examination. The percentage of visits with documented discussions did not vary significantly according to type of reminder, nor with any physician or patient characteristic. CONCLUSIONS: The use of a reminder, especially in the context of an office visit for a physical examination, significantly increased the implementation of adolescent preventive health care in this family practice center. PMID- 1453151 TI - Coding and reimbursement of primary care debridement and excision procedures. AB - Current medical practice requires physicians to accurately report services provided to patients. Patient billing for debridement and excision procedures involves the selection of specific 1992 Physicians' Current Procedural Terminology codes. Although a site-specific surgical procedure code often yields higher reimbursement than a general procedure code, physicians should select the code that most accurately reflects the procedure performed. This review identifies the codes used to report destruction and excision procedures performed by primary care physicians. Included in this review are skin debridement, burn debridement, excision of benign and malignant lesions of the skin and subcutaneous tissue, cyst and ganglion excision, nail excision, anorectal lesion excision, shave, paring, and skin tag excision procedures, and foreign body removal. The Health Care Financing Administration's relative value units and one state's published Medicaid payment rates are included for each procedure code. Instructions are provided for selecting between multiple coding options when more than one code describes the service provided. PMID- 1453152 TI - Gastroesophageal reflux disease in adults: pathophysiology, diagnosis, and management. AB - Gastroesophageal reflux disease (GERD) refers to symptoms or tissue damage that result from gastroesophageal reflux. Reflux esophagitis is a subset of GERD and implies the presence of esophageal inflammation, ie, esophageal erosions that are visible endoscopically, or nonerosive inflammation that can be documented by biopsies. Heartburn is the most common and specific symptom of GERD. In some patients, chest pain or respiratory symptoms may be the only presenting signs. In patients aged < 50 years with uncomplicated GERD, empiric therapy (typically with antacids or an H2-receptor antagonist) is appropriate. For older patients, those with complications, and those whose symptoms do not respond to empiric therapy, endoscopic evaluation is indicated. Many patients will improve with standard twice-daily dosing of an H2-receptor antagonist. However, GERD is generally more resistant to antisecretory pharmacologic therapy than is peptic ulcer disease. Those patients who fail to respond to standard dosing of an H2-receptor antagonist may get relief from high-dose H2-receptor antagonists or omeprazole therapy. PMID- 1453153 TI - Laboratory outbreak of Q fever. AB - An outbreak of Q fever in a university department where sheep placentas were being used for research is described. Of six persons exposed to the sheep, four had positive titers with only one person developing an acute febrile illness and liver disease. This report illustrates the value of the family physician obtaining an occupational history and conducting an outbreak investigation. PMID- 1453154 TI - Conducting clinical trials in practice settings. Research in progress by family physicians. PMID- 1453155 TI - Steroidogenesis in Fundulus heteroclitus. IV. Dichotomous effects of a phorbol ester on ovarian steroid production and oocyte maturation. AB - The possible role of protein kinase C (PKC) activation in mediating the stimulatory actions of a Fundulus pituitary extract (FPE) on ovarian steroidogenesis and oocyte maturation was investigated. The phorbol ester, phorbol 12-myristate 13-acetate (PMA), alone slightly increased basal 17 alpha hydroxy,20 beta-dihydroprogesterone (DHP) and 17 beta-estradiol (E2) synthesis and significantly stimulated germinal vesicle breakdown (GVBD). Addition of FPE promoted synthesis of DHP, testosterone (T), and E2, and initiated GVBD. Phorbol ester inhibited FPE-induced steroidogenesis but increased the number of oocytes that underwent GVBD. Phorbol ester also markedly impeded induction of steroidogenesis by dibutyryl cAMP and differentially affected the conversion of 25-hydroxycholesterol, pregnenolone, or progesterone to DHP, T, and E2: DHP production was not affected; T production diminished; and E2 synthesis increased (T aromatization also increased). These results suggest an inhibitory role for the PKC pathway on FPE-induced ovarian steroid production, with PMA appearing to affect various steroidogenic steps. The stimulatory action of PMA on oocyte maturation seems to be independent of follicular steroid production since aminoglutethimide, an inhibitor of steroidogenesis, did not block PMA-induced GVBD. Moreover, PMA had a marked stimulatory effect on GVBD in denuded oocytes. Thus, in contrast to the inhibitory role found for the PKC pathway on ovarian follicular steroidogenesis, activation of PKC in the oocyte may serve as a signal transducing mechanism leading to GVBD. PMID- 1453156 TI - Continuous cell movements rearrange anatomical structures in intact sponges. AB - Time-lapse cinemicrography was used to record the active movements of cells in living intact sponges. Each of the three main cell types (pinacocytes, mesohyl cells, and choanocytes) continuously moved and rearranged themselves so that the internal anatomy of the sponge was continuously remodeled. The shape and appearance of the sponges anatomical structures often changed substantially within a few hours. The most motile were the mesohyl cells, with many moving as fast as one cell-length per minute (15 microns/min). Mesohyl cell locomotion was often accompanied by displacements of spicules, canals, and choanocyte chambers; the patterns of these displacements suggested that the mesohyl cells were providing the motive forces for these rearrangements. The locomotion of the pinacocytes varied according to position: those along the outer sponge margins were most active, whereas those in other parts of the surface moved relatively little. Choanocytes were never observed to undergo independent locomotion but were always found grouped together in choanocyte chambers. These choanocyte chambers interacted with pinacocytes and mesohyl cells to form excurrent canals, which continuously moved, fused with, and branched from one another. These observations suggest that the experimental phenomenon of sponge cell reaggregation and reconstitution, discovered by H. V. Wilson, represents an extreme version of morphogenetic processes that normally go on continuously within intact sponges. The results from the present study also suggest that these cellular rearrangements are controlled by active cell movements and behavioral responses that include but are not limited to selective cell adhesion. PMID- 1453157 TI - Effects of diapause on lethal yellow (Ay/Ay) mouse embryos. AB - One of the problems in studying early acting recessive lethal genes is recognizing the homozygotes prior to their demise. Molecular probes can assist in this task, but their use generally requires removal of cells and consequent damage to the embryo, which may compromise its subsequent development. The present study was undertaken in an attempt to distinguish intact, living, lethal yellow (Ay/Ay) embryos from Ay/ae and ae/ae littermates before implantation by placing them in implantation delay or diapause. After 2 days in the reproductive tract of prepubertal females, the great majority of presumptive lethal Ay/Ay embryos has failed to hatch from the zona pellucida and they exhibited a marked deficiency of cells relative to controls, particularly in the inner cell mass. This argues against a stage-specific role for the gene in implantation. PMID- 1453158 TI - Sexually differentiated mechanisms of sterility in interspecific hybrids between Oryzias latipes and O. curvinotus. AB - Fertility of interspecific hybrids between Oryzias latipes and O. curvinotus was examined. F1 females were able to lay eggs but males were sterile. Histological examination of the ovaries of hybrids revealed that oogenesis does not proceed normally in spite of the apparent fertility. Most oocytes degenerated at the pachytene stage of the meiotic prophase, and only a few entered the diplotene stage to develop into ova. Hybrid males could induce females to spawn eggs, an indication that they had differentiated completely into true males. However, they did not produce fertile sperm. Most germ cells in testes of hybrids passes through almost the entire process of spermatogenesis, but deviations from the normal course of events were observed during spermiogenesis. The condensation of chromatin in spermatids occurred, but the diameters of sperm heads were about 1.5 fold larger than those of normal ones. Prominent abnormalities were apparent in the quantity and arrangement of microtubules in the cytoplasm. Abnormal spermatozoa were phagocytized by Sertoli cells. These observations indicate that the mechanisms of impaired gametogenesis in these interspecific hybrids are sexually differentiated. PMID- 1453159 TI - Laboratory guidelines in analytical toxicology: how to approach qualitative analysis. PMID- 1453160 TI - Facial reconstruction. PMID- 1453161 TI - Contribution of rodents to postmortem artifacts of bone and soft tissue. AB - Postmortem disturbance of human remains by rodents extends beyond production of characteristic tooth mark artifacts in dry bones. Three case examples are presented that demonstrate a spectrum of rodent damage to dry and fresh bone and to fresh and mummified soft tissue. In one case, human remains are used for nesting purposes. Rodents are also noted to be vectors of bone transport. Rodent activities can affect bone recovery, human identification, and interpretation of artifacts to bone and soft tissue. Guidelines to differentiate soft tissue artifacts caused by rodents and carnivores are suggested. PMID- 1453162 TI - Ultraviolet radiation and its role in wound pattern documentation. AB - The history of ultraviolet illumination in photography is discussed. Particular attention is devoted to the forensic aspects of ultraviolet photography as it relates to patterned injury on human skin. The authors discuss the theory underlying ultraviolet illumination of wounds on skin as well as the equipment required for this type of imaging. PMID- 1453163 TI - The detection and documentation of trace wound patterns by use of an alternative light source. AB - This article is a discussion of the use of narrow-band light sources coupled with cameras equipped with band-pass filters to document patterned injuries on human skin. Several case reports are included. PMID- 1453164 TI - A statistical analysis of successional patterns in carrion-arthropod assemblages: implications for forensic entomology and determination of the postmortem interval. AB - A set of statistical protocols is proposed for analyzing carrion-arthropod succession in forensic entomology investigations. A total of 23 carrion-arthropod data sets from temperate, tropical, desert, and coastal environments were assembled in a standard format and analyzed using randomization tests and methods derived from quantitative community ecology. The data were analyzed in three ways. First, patterns of arthropod visitation on nonhuman carcasses were analyzed in each of the 23 cases. Analysis revealed two groups of taxa: those that persist on the carcass over a single time interval (= nonreoccurring taxa, 80% of the taxa) and those that appear, leave, and reappear over time on the carcass (= reoccurring taxa, 20%). Reoccurring taxa, which can confound estimation of the postmortem interval (PMI), were found in 6 classes, 12 orders, and 29 taxonomic families of arthropods, including some forensically important taxa (for example, calliphorids, sarcophagids, histerids). The recognition that reoccurring taxa exist and that they are found in forensically important groups is an early step toward factoring in their potential importance in future entomological investigations. Second, temporal changes in the taxonomic composition of the carrion-arthropod community were studied by quantifying the degree of taxonomic similarity between pairwise combinations of time-specific samples of the succession. In 13 of the 18 illustrated cases, the midsuccessional samples, owing to their higher species richness, were taxonomically more similar to all other pairwise samples, on the average, than early and late successional samples which were poorer in species. Variability in taxonomic composition is the norm for most periods of the succession; however, in 17 of the 23 cases, some successional periods (particularly endpoint samples) revealed no changes in arthropod species composition (= matching sample-pairs). When applied to medicolegal cases, it is suggested that data sets with large fractions of matching sample-pairs should produce wider-ranging PMI estimates, on the average, than data sets with smaller fractions of matching sample-pairs. Third, Monte Carlo simulation was applied to each of the 23 assemblages to test specific hypotheses about community-wide patterns of arthropod visitation times on nonhuman carcasses. Simulation results revealed that arthropod residence times in the majority of cases (13 or 56%) followed a "clumped" succession model, whereas, the remaining 10 cases (44%) showed a more "uniform" spacing pattern of residence times on carcasses. Comparison of species accumulation curves for observed and simulated data further revealed that among the 13 "clumped" cases, most (9 or 69%) followed a "clumped, early" model (rather than "clumped, midterm" or "clumped, late" models).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1453165 TI - Transferrin (TF) typing from semen stains using isoelectric focusing and immunoblotting: correlation of TF types among blood, semen, urine, and vaginal secretion. AB - We describe a method for obtaining nondistorted and reproducible transferrin (TF) typing from liquid semen and semen stains. Isoelectric focusing of TF isoproteins on polyacrylamide gel (IEF-PAGE, pH 4 to 6.5) was accomplished using a 0.5 mm thick gel. The separated isoproteins were then visualized by immunoblotting with TF-specific antibody. Pretreatment of semen samples with neuraminidase enhanced the TF band resolution. The method was reliable, sensitive and simple, with a high resolution. When maintained at room temperature, laboratory-prepared semen stains were TF-typable for up to at least 50 weeks. The TF types in semen stains were correlated with the types found in the corresponding blood and urine samples. TF typing could therefore provide an additional discriminant characteristic in the forensic examination of semen stains. An evaluation of TF typing by IEF-PAGE and immunoblotting was also performed on casework samples submitted to our laboratory. PMID- 1453166 TI - The decision theory of paternity disputes: optimization considerations applied to multilocus DNA fingerprinting. AB - The solution of paternity disputes using results from scientific analyses is studied from a decision-theoretical viewpoint. Two alternative approaches to decision making, the so-called 'Bayes' and 'Minimax' strategies, are described and discussed. If prior probabilities of paternity are exactly known, then Bayes decisions are (a) independent of the source of evidence and (b) optimal with respect to average losses caused by wrong decisions. However, it is concluded that Minimax decisions, which depend upon the employed test system but not upon prior probabilities, are more appropriate in paternity cases if equal prior good will towards disclaimed children and alleged fathers is demanded. It is further demonstrated that, when major evidence about paternity comes from multilocus DNA fingerprinting, prior probabilities must be known quite accurately for Bayes decisions to be superior with respect to average losses. Finally, we are able to show that 'quasi' Bayes decision making, that is, adopting a neutral prior probability of 0.5 but leaving thresholds for decision making unchanged, coincides with Minimax decision making if multilocus DNA fingerprinting is employed. PMID- 1453167 TI - Comparison of fingernail striation patterns in identical twins. AB - The fingernail ridge patterns of a pair of identical twins were compared to each other, their parents, and an unrelated subject. The patterns of the twins' nails showed regions of strong similarity but were distinguishable from one another. Fewer similarities were found when comparing the nails to those of the parents and the unrelated control. The twins were shown to be monozygotic by means of DNA profiling. This therefore represents the first demonstration of unique fingernail ridge patterns in subjects shown conclusively to be identical twins. When the fingernail ridge patterns were examined with a scanning electron microscope, the backscattered electron (BEI) images were found to have superior contrast when compared to the secondary electron (SEI) images. PMID- 1453168 TI - A statistical approach to drug sampling: a case study. AB - In many countries it is left to the discretion of the court to accept or reject conclusions based on sampling procedures as applied to the total drug exhibit. As an alternative to this subjective approach, a statistical basis is presented using binomial and hypergeometric distributions to determine a lower limit for the proportion of units in a population which contains a drug, at a given confidence level. A method for calculating the total weight of a drug present in a population within a given confidence interval is also presented. In the event of no failures (all units sampled contain a drug), a sample size of six or seven units is generally sufficient to state that a proportion of at least 0.70 of the population contains a drug at a confidence level of at least 90%. When failures do occur in the sample, point estimation is used as the basis for selecting the appropriate sample size. PMID- 1453169 TI - Ion mobility spectrometry of drugs of abuse in customs scenarios: concentration and temperature study. AB - A custom-built ion mobility spectrometer has been used to obtain the IMS spectra of cocaine, heroin, amphetamine sulfate and LSD at different drug concentrations and desorption temperatures. Practical detection limits for these four drugs were obtained as a function of desorber temperature and for heroin as a function of analysis time. Spectral and ionization interferences for each of the four drugs of interest were determined. Spectral interferences by innocuous materials are few; ionization interferences occur only at very high ratios of the mass of innocuous material to that of the drug of interest. PMID- 1453170 TI - Gunshot residue particles formed by using ammunitions that have mercury fulminate based primers. AB - Ammunition having mercury fulminate-based primers are commonly manufactured by Eastern Bloc countries and used extensively in the Middle East. Gunshot residue (GSR) particles formed by firing these types of ammunition were examined. It was observed that much lower percentage of mercury-containing GSR particles were found in samples taken from a shooter as compared to the percentage of such particles in samples from cartridge cases. This fact must therefore be taken into account when interpreting case results. A plausible explanation for the results described is proposed. PMID- 1453171 TI - Linguistic evidence indicative of authorship by a member of the deaf community. AB - Documents authored by Deaf Americans were examined in order to determine if linguistic evidence indicative of this group of people is present. The native language of deaf people is not English, but rather American Sign Language (ASL). ASL is a visual-gestural language with its own principles of syntax. The evidence examined includes vocabulary, syntax, and word usage. Such characteristics are class evidence and are not a means of identification, but rather an investigative tool. Such information may be of assistance to the field investigator in either developing a suspect or limiting the number of initial suspects in a case. This research revealed that the use of ASL syntax and idioms and the problems associated with the use of English as a second language are indicative of authorship by a member of the Deaf Community. The results of this research will be of assistance to Document Examiners should they need to determine if a document was authored by a deaf individual. PMID- 1453172 TI - Family violence as a determinant factor in juvenile maladjustment. AB - The family is one of the major socialization agencies for children. Parents are one of the most important models from whom the child and adolescent acquire a wide variety of behavior patterns, attitudes, values, and norms. The aim of this study was to determine the importance of factors related to family conflicts in the genesis of social maladjustment. A total of 189 young people (110 boys and 79 girls) from training schools connected with the juvenile court in Murcia (Spain) were studied. The subjects' ages ranged from 11 to 18 years (mean 13.51, SD 0.16). Our sample comprised a group of minors who experienced a high incidence of intrafamilial pathology, which was found to be a significant discriminant factor. Aggressive behavior, rules, norms, values, opinions, and attitudes toward aggressivity can be learned in the family setting. PMID- 1453173 TI - The application of immunoblotting to the phenotyping of haptoglobin. AB - An immunoblotting method for phenotyping haptoglobin in serum and bloodstains has been developed. Haptoglobin isoproteins were separated by polyacrylamide gradient gel electrophoresis and then transferred to nitrocellulose by electroblotting. The use of 1 mm gels facilitated more rapid and effective transfer than conventional 3 mm thick gels. Nitrocellulose blots were developed by double antibody enzyme immunoassay. The detection limit for serum and bloodstains was improved 16 times compared to conventional staining using O-tolidine. The method could detect haptoglobin phenotypes from 0.001 microliter of whole blood. This detection limit is approximately 8 times lower than that of group specific component analysis by immunoblotting. PMID- 1453174 TI - Car surfing in Indiana--an unusual form of motor vehicle fatality. AB - A new form of joyride known as "car surfing" with fatal results is documented. The possible role of this activity in extra-vehicular motor vehicle deaths involving teenage or youthful drivers is described. Potential scene and autopsy findings are discussed. PMID- 1453175 TI - An unusual fatal case of accidental asphyxia in a child. AB - The death of a three-year-old child by asphyctic mechanism is described. The child was accidentally suspended by the neck from a half-opened car window. This report details the form in which the accident occurred. The influence of the type of window and the autopsy findings. PMID- 1453176 TI - Mona Lisa: the enigma of the smile. AB - The Mona Lisa, painted by Leonardo Da Vinci, 1503, pictures a smile that has been long the subject of conjecture. It is believed, however, that the Mona Lisa does not smile; she wears an expression common to people who have lost their front teeth. A closeup of the lip area shows a scar that is not unlike that left by the application of blunt force. The changes evident in the perioral area are such that occur when the anterior teeth are lost. The scar under the lower lip of the Mona Lisa is similar to that created, when, as a result of force, the incisal edges of the teeth have pierced the face with a penetrating wound. PMID- 1453177 TI - An antiplatelet aggregation principle and X-ray structural analysis of cis khellactone diester from Peucedanum japonicum. AB - Three structurally related khellactone coumarins, 1-3, were isolated from the aerial parts of Peucedanum japonicum (Umbelliferae). Compound 2 was identified as a new coumarin (cis-3'-isovaleryl-4'-senecioylkhellactone) by spectral and chemical analysis. Conformation of the dihydropyrano ring of cis-3',4' disenecioylkhellactone [3] was elucidated by X-ray crystallographic analysis. These three natural khellactone esters were subjected to the antiplatelet aggregation bioassay where cis-3',4'-diisovalerylkhellactone [1] showed significant activity (at 50 micrograms/ml). PMID- 1453178 TI - Synthesis of ellagic acid O-alkyl derivatives and isolation of ellagic acid as a tetrahexanoyl derivative from Fragaria ananassa. AB - Ellagic acid [1] is a gallic acid dimer that occurs in plants, fruits, and nuts, either in its free form, or in a series of ellagitannins, or as a glucoside. It has been shown to inhibit cancer induced by several types of chemical carcinogens including polycyclic aromatic hydrocarbons, N-nitrosamines, aflatoxin, and aromatic amines. It has been extracted from a number of fruits, including strawberries; however, its presence in the extracts was determined only by hplc connected with a diode array detector. In the present report, ellagic acid was isolated as a tetrahexanoyl derivative 2 from Fragaria ananassa and identified by 13C and 1H nmr and ms. The 13C-nmr shifts of the aromatic carbons adjacent to a hexanoyloxy group were assigned using two new synthetic model compounds: 3,3' dihexanoyloxydiphenic-2,2',6,6'-dilactone [3] and 4,4'-dihexanoyloxydiphenic 2,2',6,6'-dilactone [4]. Two new derivatives of ellagic acid [1],3,3'-di-beta-D glucopyranosylellagic acid decaacetate [5] and 3,3'-di-n-octyl-4,4' dihexanoylellagic acid [7], were also synthesized. Both derivatives were less effective as inhibitors of benzo[a]pyrene tumorigenesis in the lungs of strain A/J mice than ellagic acid. PMID- 1453179 TI - Diterpene metabolites from two chemotypes of the marine sponge Myrmekioderma styx. AB - Three apparent chemotypes of the marine sponge Myrmekioderma styx exist. An acyclic diterpene, styxenol A [1], has been isolated from the shallow water chemotype, while three tricarbocyclic diterpenes 3, 6, and 7 have been isolated from the deep chemotype. The structures were elucidated based on spectral methods including homo- and hetero-nuclear 2D nmr experiments. Compounds 1, 3, and 6 exhibit moderate cytotoxicity against the P-388 murine leukemia cell line and the A549 human lung tumor cell line. PMID- 1453180 TI - Antibacterial activity of totarol and its potentiation. AB - Antimicrobial activity of six diterpenoids isolated from the bark of Podocarpus nagi (Podocarpaceae) has been tested against twelve selected microorganisms. Totarol [1], the most abundant compound among the six, exhibited potent bactericidal activity only against Gram-positive bacteria, among which Propionibacterium acnes was the most sensitive bacterium. Totarol also showed strong activity against four other Gram-positive bacteria tested: Streptococcus mutans, Bacillus subtilis, Brevibacterium ammoniagenes, and Staphylococcus aureus (both penicillin-resistant and penicillin-susceptible strains). The bactericidal activity of totarol was enhanced when it was tested in combination with several other natural products. Noticeably, the activity of totarol against Sta. aureus was increased eightfold when tested in combination with 1/2MIC of anacardic acid [9]. The synergistic activity of anacardic acid caused the minimum bactericidal concentration (MBC) of totarol to be lowered from 1.56 to 0.2 micrograms/ml. PMID- 1453181 TI - New trichoverroids from Myrothecium verrucaria isolated by high speed countercurrent chromatography. AB - Three new double-bond isomers of the trichothecene trichoverrins (3, 4a and 4b) have been isolated, principally through the use of high speed countercurrent chromatography, which proved to be a powerful tool in the separation of these closely related structural isomers. PMID- 1453182 TI - Bioactive constituents from the twigs of Asimina parviflora. AB - The EtOH extract of Asimina parviflora (Annonaceae), when subjected to activity directed fractionation using lethality to brine shrimp, led to the isolation and identification of five bioactive compounds: asimicilone [1], which is a new 2 quinolone alkaloid, 6-cis-docosenamide [2], which is a new amide of a long hydrocarbon chain fatty acid, and three known compounds, asimicin, (+) syringaresinol, and beta-sitosterol-beta-D- glucopyranoside. The structure determination of the new alkaloid was performed by extensive nmr analyses, including HMQC and HMBC. Selective cytotoxic activities of these compounds in three human solid tumor cell lines are also reported. PMID- 1453183 TI - Antitumor agents, 135. Structure and stereochemistry of polacandrin, a new cytotoxic triterpene from Polanisia dodecandra. AB - A new dammarane triterpene, polacandrin [1], has been isolated from Polanisia dodecandra. The structure of 1 was established as 1 beta, 3 alpha, 12 beta, 25 tetrahydroxy-20(S),24(S)-epoxydammarane by chemical and spectroscopic methods, which included the concerted application of a number of 2D nmr techniques that involved 1H-1H COSY, HETCOR, NOESY, and long-range HETCOR. Single-crystal X-ray analysis of polacandrin pentahydrate verified the complete structure and stereochemistry. Polacandrin showed potent cytotoxicities against KB (ED50 = 0.60 microgram/ml), P-388 (ED50 = 0.90 microgram/ml), and RPMI-7951 (ED50 = 0.62 microgram/ml) tumor cells. PMID- 1453184 TI - Two new alkaloids from Xestospongia sp., a New Caledonian sponge. AB - Five alkaloids have been isolated from a New Caledonian sponge Xestospongia sp. These include three known xestospongin derivatives, the new demethylxestospongin B (1) and a tetrahydrocarboline derivative 5. The structures of the new compounds 1 and 5 have been established by nmr studies and comparison with previously described products. PMID- 1453185 TI - Experimental and clinical evaluation of a noninvasive reflectance pulse oximeter sensor. AB - The objective of this study was to evaluate a new reflectance pulse oximeter sensor. The prototype sensor consists of 8 light-emitting diode (LED) chips (4 at 665 nm and 4 at 820 nm) and a photodiode chip mounted on a single substrate. The 4 LED chips for each wavelength are spaced at 90-degree intervals around the substrate and at an equal radial distance from the photodiode chip. An optical barrier between the photodiode and LED chips prevents a direct coupling effect between them. Near-infrared LEDs (940 nm) in the sensor warm the tissue. The microthermocouple mounted on the sensor surface measures the temperature of the skin-sensor interface and maintains it at a present level by servoregulating the current in the 940-nm LEDs. An animal study and a clinical study were performed. In the animal study, 5 mongrel dogs (weight, 10-20 kg) were anesthetized, mechanically ventilated, and cannulated. In each animal, arterial oxygen saturation (SaO2) was measured continuously by a standard transmission oximeter probe placed on the dog's earlobe and a reflectance oximeter sensor placed on the dog's tongue. In the first phase of the experiment, signals from the reflectance sensor were recorded while the dog was immersed in ice water until its body temperature decreased to 30 degrees C. In the second phase, the animal's body temperature was normal, and the oxygen content of the ventilator was varied to alter the SaO2. In the clinical study, 18 critically ill patients were monitored perioperatively with the prototype reflectance sensor. The first phase of the study investigated the relationship between local skin temperature and the accuracy of oximeter readings with the reflectance sensor. Each measurement was taken at a high saturation level as a function of local skin temperature. The second phase of the study compared measurements of oxygen saturation by a reflectance oximeter (SpO2[r]) with those made by a co-oximeter (SaO2[IL]) and a standard transmission oximeter (SpO2[t]). Linear regression analysis was used to determine the degree of correlation between (1) the pulse amplitude and skin temperature; (2) SpO2(r) and SaO2(IL); and (3) SpO2(t) and SaO2(IL). Student's t test was used to determine the significance of each correlation. The mean and standard deviation of the differences were also computed. In the animal study, pulse amplitude levels increased concomitantly with skin temperature (at 665 nm, r = 0.9424; at 820 nm, r = 0.9834; p < 0.001) and SpO2(r) correlated well with SaO2(IL) (r = 0.982; SEE = 2.54%; p < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1453186 TI - Noninvasive cardiac output determined with a new method based on gas exchange measurements and carbon dioxide rebreathing: a study in animals/pigs. AB - A system has been designed to determine cardiac output noninvasively. The system's main component is a closed breathing circuit and it measures oxygen uptake (VO2), carbon dioxide elimination (VCO2), and end-tidal CO2 partial pressure (PET). As an integral part of the system, periods of CO2 rebreathing can be automatically implemented. The CO2 partial pressure of oxygenated mixed venous blood (Pv) is obtained from the measured exponential rise of the PET value during such a CO2 rebreathing maneuver. A new method is described for estimating the pulmonary blood flow, alveolar ventilation, cardiac output (CO), and mixed venous oxygen saturation (SVO2) from PV, PET, VO2, VCO2, tidal volume, and arterial oxygen saturation. The method was evaluated in 6 anesthetized and mechanically ventilated pigs. A wide range of cardiac output, shunt fractions, and dead space to tidal volume ratios were induced by combinations of bronchoalveolar lavage, hypervolemia, hypovolemia, and variable levels of positive end-expiratory pressure (PEEP). The bias between the CO obtained with the noninvasive technique (CO L/min) and the thermodilution CO (Qt L/min) was 0.13 L/min (SD = 0.78 L/min) and the correlation was N = 64; R = 0.92; CO = 0.95*Qt + 0.38. The bias obtained for double determinations with the noninvasive CO technique was 0.3 L/min (SD = 0.5 L/min). The bias between the noninvasive estimates of Svo2 and the directly measured values was 1.1% (SD = 9.3%). For double determination with the noninvasive technique the bias was -0.9% (SD = 4.7%). It is concluded that in mechanically ventilated pigs the proposed method produces good estimates of CO and SVO2 also in the presence of significant ventilation/perfusion mismatch. PMID- 1453187 TI - Methods to produce calibration mixtures for anesthetic gas monitors and how to perform volumetric calculations on anesthetic gases. AB - A simple procedure for making calibration mixtures of oxygen and the anesthetic gases isoflurane, enflurane, and halothane is described. One to ten grams of the anesthetic substance is evaporated in a closed, 11,361-cc glass bottle filled with oxygen gas at atmospheric pressure. The carefully mixed gas is used to calibrate anesthetic gas monitors. By comparison of calculated and measured volumetric results it is shown that at atmospheric conditions the volumetric behavior of anesthetic gas mixtures can be described with reasonable accuracy using the ideal gas law. A procedure is described for calculating the deviation from ideal gas behavior in cases in which this is needed. PMID- 1453188 TI - Evaluation of users' abilities to recognize musical alarm tones. AB - The problem of accurate identification of alarm sounds in the operating room, recovery room, and intensive care environment has persisted for many years. Monitors made by different companies may have different alarm sounds for the same monitored variable, and similar alarm sounds for different variables. In an effort to illustrate universal alarms sounds, a system of six musical alarm tones was designed with musical themes from popular songs used for oxygenation, ventilation, cardiovascular monitoring, temperature monitoring, artificial perfusion, and drug administration systems. These melodies were played for a group of anesthesiologists and others, who were initially asked to guess the organ system for each melody. The answers were then given to the participants, and after a short delay the melodies were played again in a different order. Seventy-nine response sheets were collected. The expected random score was 1.0 +/ 1.0 SEM correct. The observed score on the first hearing was 1.5 +/- 1.6 SEM, p = 0.01 compared with the random score. The observed score on the second testing was 4.3 +/- 2.2 SEM, p = 0.001 compared with the first hearing. Indeed, 42 of 79 (53%) respondents got all six answers correct on the second testing, versus three respondents for the first testing. The implications of these findings are discussed in the context of integrated alarm systems used in complex medical environments such as the operating room. PMID- 1453189 TI - A widely unappreciated cause of failure of an automatic noninvasive blood pressure monitor. AB - Many anesthesiologists have come to depend on automatic noninvasive blood pressure monitoring to obtain blood pressure (BP) readings. A case is presented in which, during a critical phase of the anesthetic, an automatic noninvasive blood pressure (ANIBP) device not only failed to provide meaningful clinical data but, in fact, gave an error message that was misleading. At the time of the message, the patient was noted to be in ventricular trigeminy at a rate of 92 beats/min. It appears that the repetitive beat-to-beat fall in blood pressure due to the dysrhythmia "fooled" the automatic noninvasive blood pressure device's software algorithm into believing that there was an air leak in the system. Thus, in addition to pointing out an unappreciated and potentially troubling device related critical event, the present case demonstrates the importance of good human factors design for medical devices used in the critical care setting. In particular, the issue is raised of how medical devices should deal with uncertain or potentially misleading data. PMID- 1453190 TI - Anesthesia systems. Part 1: Operating principles of fundamental components. AB - This article is the first in a two-part series on the operation of principal components within Narkomed anesthesia systems. Part 1 illustrates the structure and function of various sections of the machine's internal piping, including components of the pneumatic circuit and the oxygen flush valve, and several safety features, such as the oxygen supply pressure alarm, oxygen failure protection device, and oxygen ratio monitor controller. The article progresses to other basic components of the anesthesia system. Topics include the function of the absorber unit and the flow of gas through it, the principle of operation of the positive end-expiratory pressure valve, the function and mechanics of the adjustable pressure limiter valve, and the open reservoir scavenger system. Part 1 is a valuable tool in understanding the function and pneumatics of the primary components of the anesthesia system. PMID- 1453191 TI - Patient-related data management. AB - Patient-related data management (PDM) has become an increasingly important and time-consuming task in intensive care medicine. Currently, all data are usually collected in a poorly structured patient chart consisting of forms and pictures, with about 400 manual entries a day. To handle this amount of data, we have designed a three-level patient system: level 1, summarizing the whole patient; level 2, summarizing one organ system or one isolated problem; and level 3, variables describing morphology and function of organ systems. PDM must be adapted to different clinical situations. We observed three different scenarios: (1) Exploratory PDM, where the clinician learns about the patient and builds up an individual patient model in his or her mind. (2) Operational PDM, where in routine care clinicians are part of a feedback control system, in which they use the patient-related model. (3) Summary PDM, where a clinician summarizes all the information gathered during a period when he or she was responsible for the patient. Computing tools based on clinical thinking and adapted to different situations can ensure accurate, clear, and concise patient care communication among the members of the intensive care staff. PMID- 1453192 TI - How can a standard software package for data management in anesthesia be achieved? AB - Collecting data for administrative, statistical, medical, and organizational purposes is becoming increasingly important in anesthesia. In 1986 the Swiss Society for Anesthesiology decided to create a program that would be compatible for different computers and would expedite data collection. The system developed was called Information System for Operations (ISOP), which was written in the database and programming system Massachusetts General Hospital Utility Multi Programming System (MUMPS). It was installed in eight hospitals and met the initial requirements, but the individual requirements of the hospitals were greatly underestimated. MUMPS has an impressive data storage capability and handling when used in a personal computer (PC) network. The user-interface, however, is inferior to other PC packages, partly because windowing and mouse support were not implemented when the ANSI standard was set. Improved statistical programs, a module for on-line data acquisition, and intensive care unit (ICU) use will be additional modules to the program. PMID- 1453193 TI - Computerization of anesthesia information management: yet another application. PMID- 1453194 TI - Anesthesia machine check. PMID- 1453195 TI - Quality-of-life assessment: performance status upstaged? PMID- 1453196 TI - Cancer pain: from curriculum to practice change. PMID- 1453197 TI - Prognostic value of quality-of-life scores during chemotherapy for advanced breast cancer. Australian New Zealand Breast Cancer Trials Group. AB - PURPOSE: We observed that quality-of-life (QL) scores, collected to evaluate treatment in a randomized trial in advanced breast cancer, predicted survival duration. This report explores the prognostic associations between QL and survival in more detail. PATIENTS AND METHODS: In a randomized clinical trial comparing intermittent and continuous therapy policies for patients with advanced breast cancer, QL was measured by linear analog self-assessment (LASA) and the Quality-of-Life Index (QLI). Baseline scores and subsequent changes were included in statistical models of survival duration, with and without other prognostic factors. RESULTS: Physician assessment of QLI and patient LASA scores for physical well-being (PWB), mood, nausea and vomiting, appetite, and overall QL (but not pain) at the commencement of treatment were significant predictors of subsequent survival. Scores for PWB and QLI were independent of other prognostic factors. Changes in scores were also prognostically important. Both baseline and change in scores for PWB, mood, pain, and QLI after the first three treatment cycles, but before an arbitrary 180-day time point, were significantly predictive of survival beyond that time. Both QLI and PWB were prognostically independent of tumor response. Although QL improvement was correlated with tumor response, continuous therapy yielded significantly better QL scores, even in nonresponders. CONCLUSION: These findings support the validity of the simple QL measures used in the trial. They are compatible with the simple explanation that patients perceive disease progression before it is clinically evident, but also with a causal relationship between QL and survival duration. PMID- 1453198 TI - Prognostic value of DNA flow cytometry in the locally recurrent, conservatively treated breast cancer patient. AB - PURPOSE: This study attempted to determine the prognostic value of DNA flow cytometry in the treatment of patients with locally recurrent, conservatively treated breast cancer. METHODS AND MATERIALS: Of 433 patients with clinical stage I and II breast cancer treated with conservative surgery and radiotherapy at Yale New Haven Hospital before January 1985, 50 patients experienced an ipsilateral breast relapse as a first site of treatment failure. Using standard flow cytometric techniques, DNA ploidy, DNA index, and S-phase fraction (SPF) were measured for 38 of the 50 (76%) paraffin-embedded specimens available for analysis. RESULTS: At a median postrecurrence follow-up of 5.8 years, the 5-year and disease-free survival rates following ipsilateral breast treatment failure were 48% and 54%, respectively. Sixty-three percent of the recurrent tumors were DNA diploid and 37% were aneuploid. Both DNA ploidy and SPF were statistically significant prognostic indicators for 5-year survival and disease-free survival after local recurrence. The 5-year survival rate of the DNA diploid population was 64%, compared with 15% in the aneuploid population (P < .02). Patients with low SPF (< 12%) experienced an 83% 5-year survival rate, compared with a 24% 5 year survival rate in patients with high SPF (> or = 12%) (P < .03). Ploidy and SPF were combined to define the categories of favorable (diploid, low SPF) and unfavorable (diploid, high SPF or any aneuploid subgroups). Patients in the favorable category experienced an 89% 5-year postrecurrence survival rate and a 100% disease-free survival rate, whereas patients in the unfavorable category had a 24% 5-year survival rate and a 32% disease-free survival rate (P < .01). The flow cytometry as a factor correlated with other clinical parameters previously shown to be of prognostic significance in this patient population. In a multivariate analysis, flow cytometry was a statistically significant and independent prognostic factor for disease-free survival following local recurrence. CONCLUSIONS: DNA ploidy and SPF as measured by currently available flow-cytometric techniques show promise as a tool in determining prognosis for the patient with locally recurrent breast cancer. Implications of these findings with respect to issues of adjuvant systemic therapy at the time of local recurrence are discussed. PMID- 1453199 TI - Adjuvant therapy with a doxorubicin regimen and long-term tamoxifen in premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial. AB - PURPOSE: A randomized trial was performed in premenopausal postoperative women with ipsilateral axillary node-positive (N+) breast carcinoma and known estrogen receptor (ER) status to assess the efficacy of an Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-based induction regimen and 5 or more years of tamoxifen (Tam). PATIENTS AND METHODS: Patients received 12 28-day cycles of cyclophosphamide 100 mg/m2 orally days 1 to 14, methotrexate 40 mg/m2 intravenously (IV) days 1 and 8, fluorouracil 600 mg/m2 IV days 1 and 8, prednisone 40 mg/m2 orally days 1 to 14, and Tam 10 mg orally twice daily (CMFPT), or the same regimen plus halotestin 10 mg orally twice daily (CMFPTH) alternating monthly with 22-day cycles of vinblastine 4.5 mg/m2 IV day 1, Adriamycin 45 mg/m2 IV day 1, thiotepa 12 mg/m2 IV day 1, halotestin, and Tam (ALTER). Prednisone in the ALTER regimen was stopped after the second CMFPTH cycle. After 12 cycles, patients were again randomized to stop or continue Tam. After 5 years, patients on Tam were again randomized to continue or stop Tam; the results from this randomization are still coded. Among 533 analyzed induction cases, 263 received CMFPT and 270 ALTER. Among 396 analyzed maintenance cases, 201 continued Tam and 195 were observed. Pretreatment characteristics were balanced among treatments. The median follow-up times are 5.1 years for induction and 4.1 years for maintenance. RESULTS: The time to relapse (TTR) was superior for the ALTER regimen (P = .04) and for the maintenance Tam (P = .05). Overall survival comparisons between the regimens are not statistically different. A longer TTR was associated with decreasing nodal involvement, ER+ status, and increasing age. The favorable effects of decreasing nodal involvement and ER+ status carried over to survival; a progesterone receptor-positive (PgR+) status and decreasing tumor size were also associated with longer survival. Development of amenorrhea was associated with improved TTR and survival. Toxicity was similar for the two induction regimens and for the two maintenance regimens. Overall relapse patterns were similar among the induction regimens, but continuing Tam led to fewer locoregional relapses. CONCLUSION: The results suggest significant overall TTR therapeutic benefits of an Adriamycin-containing alternating induction regimen and of continuing maintenance Tam therapy for at least 5 years. PMID- 1453200 TI - Treatment of recurrent and refractory pediatric solid tumors with high-dose busulfan and cyclophosphamide followed by autologous bone marrow rescue. AB - PURPOSE: The purpose of this study was to determine the toxicities of and responses to high-dose busulfan and cyclophosphamide with autologous bone marrow transplant (ABMT) in patients with recurrent or refractory pediatric solid tumors. PATIENTS AND METHODS: We treated 18 patients (ages, 2 to 38 years; median, 14) who had tumors that were resistant to conventional chemotherapy and radiotherapy with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg. Seventeen patients received bone marrow purged with 4-hydroperoxycyclophosphamide; one received unpurged marrow. RESULTS: Despite extensive prior treatment, including radiotherapy in 16 patients, toxicity generally was acceptable. For seven patients with measurable disease, there were three partial responses of 2, 10, and 20 months' duration, three patients with stable disease (SD), and one early, toxic death. Of the 11 patients with no measurable disease at the time of transplantation, one patient with osteosarcoma continues in remission at 57+ months and one third of the patients survived for at least 16 months. Mucositis was the predominant nonhematopoietic toxicity. CONCLUSION: Although the high-dose busulfan and cyclophosphamide combination showed modest activity, changes in the preparative regimen should be considered to improve the response rate in refractory tumors. PMID- 1453201 TI - Improvement in outcome for children receiving allogeneic bone marrow transplantation in first remission of acute myeloid leukemia: a report from the Groupe d'Etude des Greffes de Moelle Osseuse. AB - PURPOSE: We retrospectively analyzed the outcome of children with acute myeloid leukemia (AML) in first complete remission (CR) who received HLA-identical bone marrow transplantation (BMT) in 13 French transplant centers. PATIENTS AND METHODS: Seventy-four children were treated from June 1979 through December 1990. The conditioning regimen included total-body irradiation (TBI) in 54 cases and busulfan in 20. Prophylaxis of graft-versus-host disease (GVHD) consisted of cyclosporine (CycloA) plus methotrexate (MTX) for 38 patients, MTX for 17, CycloA for 18, and T depletion without other prophylaxis for one. The mean value of the interval from diagnosis to transplantation was 167 days. RESULTS: Sixteen patients died of transplant-related complications, 12 relapsed, and 46 are alive in continuous remission with a median follow-up of 46 months. We examined results obtained over three successive periods: 1979 to 1982 (n = 14 children), 1983 to 1986 (n = 29), and 1987 to 1990 (n = 31). Probabilities of event-free survival (EFS) were 43%, 48%, and 82% for the three successive periods, respectively (P < .02). This improvement in EFS was linked to a decreased risk of transplant related mortality: 36%, 36%, and 3%, respectively (P < .01). Other factors associated with a better EFS in the univariate analysis were a short time interval from diagnosis to transplant (< 120 days), the absence of significant (grade > or = 2) acute GVHD, and the absence of chronic GVHD. In the multivariate analysis, two factors had a favorable impact on long-term survival: the year of transplantation (years 1987 to 1990 v others) and the absence of acute GVHD. CONCLUSION: The outcome for children receiving allogeneic BMT in first CR of AML has improved in France during recent years. PMID- 1453202 TI - Standard-dose and high-dose peptichemio and cisplatin in children with disseminated poor-risk neuroblastoma: two studies by the Italian Cooperative Group for Neuroblastoma. AB - PURPOSE: The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor risk neuroblastoma. PATIENTS AND METHODS: From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT). RESULTS: Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5). CONCLUSION: Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established. PMID- 1453203 TI - Residual disease at the end of induction therapy as a predictor of relapse during therapy in childhood B-lineage acute lymphoblastic leukemia. AB - PURPOSE: More than 95% of children with B-lineage acute lymphoblastic leukemia (ALL) achieve a clinical remission after the induction phase of chemotherapy (first 28 days) as evaluated by morphologic criteria. However, relapse occurs in approximately 30% of these children. The objective of this study was to determine whether the outcome of patients in clinical remission at the end of induction therapy could be predicted using a highly sensitive method to detect residual disease. PATIENTS AND METHODS: All children diagnosed with B-lineage ALL at the Children's Hospital of Philadelphia during a 2-year period were eligible. The extent of residual leukemia was quantitated in remission marrow samples obtained at the end of induction therapy in 44 children using a phage clonogenic assay in association with complementarity-determining-region 3 (CDR3)-polymerase chain reaction (PCR). RESULTS: Residual disease was a significant predictor of outcome independent of WBC count, age, or sex. The estimated relapse-free survival (RFS) during therapy was 50.4% (+/- 12.6%) for patients with high residual disease (> or = 0.6% leukemia cells among total marrow B cells) versus 91.9% (+/- 5.5%) for those with lower levels (P < .002). There were no significant differences in off treatment RFS between patients with high or low residual disease who completed therapy in continuous remission (P = .82). The overall estimated RFS was 32.3% (+/- 11.6%) for patients with high residual disease versus 62.6% (+/- 10.7%) for patients with lower levels of residual leukemia cells, with a median follow-up of 5.3 years for patients in continuous remission (P < .008). CONCLUSION: PCR detection of high residual disease at the end of induction therapy identifies patients at increased risk for relapse during therapy. PMID- 1453204 TI - Phase I/II study of iodine 131 metaiodobenzylguanidine in chemoresistant neuroblastoma: a United Kingdom Children's Cancer Study Group investigation. AB - PURPOSE: The goal of this study was to evaluate the toxicity of iodine 131 metaiodobenzylguanidine (mIBG) in metastatic neuroblastoma. PATIENTS AND METHODS: A multicenter phase I study of 131I mIBG has been undertaken by the United Kingdom Children's Cancer Study Group (UKCCSG) in children with advanced chemoresistant neuroblastoma. Activity prescription was based on a prescribed whole-body radiation dose, which was established for individual patients by performing an initial tracer investigation with 75 MBq of 131I mIBG. An activity was derived from this pharmacokinetic study that would deliver an initial whole body-absorbed radiation dose of 1 Gy. Subsequent dose escalations were based on observed toxicity. RESULTS: Twenty-five patients, aged 1 to 10 years, were treated with prescribed whole-body dose levels of 1.0 Gy (n = 2), 2.0 Gy (n = 13), and 2.5 Gy (n = 10). This necessitated administration of 2.4 to 12.1 GBq of activity. Hematologic, hepatic, kidney, and adrenal toxicity were observed, with bone marrow suppression being the principal dose-limiting toxicity. Bone marrow toxicity increased with prescribed whole-body-absorbed radiation dose, with 80% of patients developing grade 3 or 4 thrombocytopenia at a prescribed whole-body radiation dose of 2.5 Gy. Objective evidence of tumor response was seen in soft tissue (primary or nodal disease), bone, and bone marrow, with an overall response rate of 33% (partial response, n = 8; static disease, n = 9; progressive disease, n = 7). CONCLUSIONS: This study has established an effective method of activity prescription that predicts subsequent toxicity, with the maximally tolerated dose being sufficient activity to deliver a whole-body-absorbed radiation dose of 2.5 Gy. The objective response rate is comparable to other single agents in chemoresistant neuroblastoma and suggests that 131I mIBG may be a useful method for targeting radiotherapy in metastatic neuroblastoma. PMID- 1453205 TI - Plasma pharmacokinetics and pharmacodynamics of a new prodrug N-l leucyldoxorubicin and its metabolites in a phase I clinical trial. AB - PURPOSE: N-l-leucyldoxorubicin (Leu-Dox) was developed as a prodrug of doxorubicin (Dox) to circumvent the cardiotoxicity associated with repeated administration of Dox. Our purpose was to assess the pharmacokinetics of Leu-Dox, Dox, doxorubicinol (Dol) and four other metabolites for pharmacokinetically guided dose-escalation and to verify the prodrug character of Leu-Dox. PATIENTS AND METHODS: Blood and urine of 14 patients were sampled during the phase I clinical trial and analyzed by high-performance liquid chromatography. Dose levels of Leu-Dox ranged from 18 mg/m2 to 225 mg/m2, the maximum-tolerated dose (MTD). Hematologic parameters were monitored regularly in each patient. RESULTS: Leu-Dox was rapidly distributed (half-life at alpha phase [t1/2 alpha] = 2.5 +/- 0.6 minutes) followed by a biphasic elimination (half-life at beta phase [t1/2 beta] = 17.4 +/- 7.3 minutes; half-life at gamma phase [t1/2 gamma] = 1.5 +/- 0.5 hours), as measured over the first 12 hours after administration. In three patients, in whom Leu-Dox was found in the plasma for up to 48 hours after injection, a final elimination half-life (t1/2,elim) of 16 hours was observed. The t1/2,elim of Leu-Dox was short (0.6 to 16.5 hours) compared with the t1/2,elim of Dox (38 +/- 11 hours). The mean residence time and apparent volume of distribution were 23 +/- 5 minutes and 19 +/- 6 L/m2, respectively. Only 1.5% to 5% of the dose was excreted in the urine over 48 hours, with Dox as major constituent. Dox was rapidly formed, reaching its maximum concentration within 10 minutes after the end of Leu-Dox infusion. Areas under the plasma concentration versus time curve (AUC infinity, mean +/- SD, n = 16) of Leu-Dox, Dox, and Dol were 115 +/- 27 mumol.min/L, 41 +/- 12 mumol.min/L, and 33 +/- 14 mumol.min/L after a dose of 60 mg/m2 Leu-Dox (= 86 mumol/m2). After the same molar dose of Dox (50 mg/m2 = 86 mumol/m2), the AUC infinity of Dox was 179 mumol.min/L, indicating that Leu-Dox was converted into Dox for 23% in the plasma compartment. The AUCs infinity of Leu-Dox, Dox, and Dol increased linearly with the dose. Negligible AUCs were observed for the other four metabolites. The AUCs infinity of Leu-Dox and Dox at the MTD (517 and 145 mumol.min/L, respectively) were lower than those in mice at the LD10 (1,930 and 798 mumol.min/L, respectively), which means that the MTD could not be predicted from the preclinical pharmacokinetics in mice. Hematologic toxicity, especially the WBC count, appeared to correlate much better with the AUC of Dox (r = .91) than with the AUC of Leu-Dox (r = .74), thus confirming the prodrug character of Leu-Dox. CONCLUSIONS: Dox is rapidly formed from Leu-Dox, and seems causative in the observed myelotoxicity. The MTD could not be predicted from the AUC at the LD10 in mice. PMID- 1453206 TI - Phase II study of pentostatin and intermittent high-dose recombinant interferon alfa-2a in advanced mycosis fungoides/Sezary syndrome. AB - PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of alternating administration of pentostatin (deoxycoformycin [DCF]) and interferon alfa-2a (IFN) in patients with advanced or refractory mycosis fungoides (MF) or the Sezary syndrome (SS). PATIENTS AND METHODS: Forty-one patients underwent therapy with alternating cycles of DCF 4 mg/m2 intravenously (IV) days 1 through 3 and IFN 10 million U/m2 intramuscularly (IM) day 22, and 50 million U/m2 intramuscularly (IM) days 23 through 26. Twenty-nine patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), six had not responded to topical therapies, and six had no previous treatment. RESULTS: Two patients achieved a complete response (CR) and 15 achieved a partial response (PR), for an overall response rate of 41% (95% confidence interval, 26% to 58%). No responses were observed in the seven patients with visceral involvement. The median progression-free survival of patients who responded was 13.1 months. IFN-related constitutional symptoms were reported in 39% of patients; severe toxicities included cardiomyopathy in one patient, acute and chronic pulmonary dysfunction in four, and reversible mental status changes in two. Seven patients developed herpes zoster during therapy and six had staphylococcal bacteremia. CONCLUSION: These results suggest that the combination of DCF and IFN is an active regimen in MF patients without visceral involvement. PMID- 1453207 TI - Preoperative systemic chemotherapy followed by adjuvant postoperative intraperitoneal therapy for gastric cancer: a University of Southern California pilot program. AB - PURPOSE: A clinical trial for patients with gastric cancer amenable to curative resection was undertaken to determine feasibility and response to preoperative systemic chemotherapy followed by postoperative intraperitoneal (IP) chemotherapy. METHODS AND MATERIALS: Thirty-eight patients with resectable gastric tumor received two cycles of protracted intravenous (IV)-infusion fluorouracil (5FU), 200 mg/m2/d, for 3 weeks with weekly IV leucovorin 20 mg/m2 and IV cisplatin 100 mg/m2 days 1 and 29. Resection of the gastric tumor followed within 3 weeks of completion of systemic chemotherapy. Those who had all visible tumor removed with clear margins received two cycles of IP floxuridine 3,000 mg (total dose) per day for 3 days and IP cisplatin 200 mg/m2 with IV sodium thiosulfate on the fourth day of IP therapy. RESULTS: Thirty-seven of 38 patients (97%) received two cycles of systemic chemotherapy. Thirty-five of 38 patients (92%) underwent laparotomy for gastric tumor resection. Thirty-three patients (87%) had gastric resections performed; 29 (76%) had all visible tumor removed with microscopically negative margins. No operative mortality was encountered. Twenty-six patients (68%) received IP treatment. IV neoadjuvant treatment was well tolerated and resulted in 68% of the patients reporting improvement in abdominal pain, 45% objective remissions by computed tomography (CT), 38% objective remissions by gastroscopy and biopsy, and 8% had complete surgical pathologic response. Neutropenic sepsis during the IP treatment phase contributed to the only treatment-related death. Four of 29 completely resected patients (14%) have had tumor recurrence. The median follow-up time of patients remaining alive is now 19 months. The median survival for 38 patients entered onto this protocol has not been reached at 17+ months. CONCLUSION: This novel approach to the treatment of adenocarcinoma of the stomach is feasible. The neoadjuvant systemic therapy results in significant primary tumor regression. The determination of whether systemic or IP components of the program contribute to decreased recurrence or increased survival awaits a prospectively randomized clinical trial. PMID- 1453208 TI - A prospective randomized trial comparing the infectious and noninfectious complications of an externalized catheter versus a subcutaneously implanted device in cancer patients. AB - PURPOSE: To compare the frequency of infectious episodes or other problems occurring with an externalized catheter (Hickman) versus a subcutaneously implanted device (Port-a-Cath, Pharmacia, Piscataway, NJ) in cancer patients, we performed a prospective, randomized study in 100 cancer patients (age range, 5 to 74 years). PATIENTS AND METHODS: Patients who were chemotherapy candidates and required an indwelling catheter were monitored prospectively and evaluated during the 180 days after the insertion of the catheter and again at time of study closure. The frequency of catheter use, reason for access, and any problems that might have been related to catheter use were noted. All data were collected prospectively and included the patient's age, sex, underlying malignancy, temperature, and leukocyte and absolute granulocyte counts at the time of catheter insertion and when complications occurred. The time to and reason for removal of the catheter, as well as any intercurrent infectious or mechanical problems, were also determined. RESULTS: Most of the infections that occurred were caused by gram-positive organisms, especially staphylococci or streptococci. A total of 22 complications (11 in each group) resulted in removal of the central line. Only one infection in the Hickman catheter group and four in the Port-a Cath group led to removal of the central line. All other infectious episodes were successfully treated without removal of the catheters. The mean device life was 230 days for the Hickman catheter and 318 days for the Port-a-Cath (not significant). CONCLUSION: There were no differences between the two study groups regarding incidence of documented infections or mechanical or thrombotic complications. PMID- 1453209 TI - Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP. AB - PURPOSE: We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy. PATIENTS AND METHODS: Thirty one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT. RESULTS: Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity. CONCLUSION: ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment. PMID- 1453210 TI - Clinical evaluation of MGI 209, an anesthetic, film-forming agent for relief from painful oral ulcers associated with chemotherapy. AB - PURPOSE: This open-label, multicenter trial evaluated the efficacy of a mucoadherent, anesthetic medication (MGI 209) for relief from painful oral ulcers associated with cytotoxic chemotherapy. PATIENTS AND METHODS: Twenty-eight eligible cancer patients who had up to five discrete oral ulcers (total area < or = 5 cm2) completed this study. Mean age was 53.5 years (range, 21 to 81). Subjective assessments of oral discomfort before and after an orange juice pain challenge (OJPC), which was measured using a visual analog scale (VAS), and visual estimates of the amount of MGI 209 that remained on treated ulcers were collected at (1) baseline (before MGI 209 treatment); and (2) 30, 60, 120, and 180 minutes posttreatment. RESULTS: Most subjects had low VAS scores (4 or less), which was indicative of oral discomfort, at baseline before and after the OJPC. At 30, 60, 120, and 180 minutes after MGI 209 treatment, most subjects had high VAS scores before and after an OJPC compared with baseline scores, which was indicative of a substantial increase in oral comfort; these differences were statistically significant (P < .0001). Mean percent of MGI 209 estimated to remain on ulcers at the previously mentioned times was 93.7%, 90.3%, 79.6%, and 71.3% of the total amount applied, respectively. CONCLUSION: Benzocaine hydrochloride in combination with the protective, mucoadherent film-coating relieved discomfort for at least 3 hours even with exposure to an irritating beverage. MGI 209 treatment should allow patients with chemotherapy-induced oral ulcers to drink and eat with significantly diminished pain or no pain. PMID- 1453211 TI - Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting. AB - PURPOSE: This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis. PATIENTS AND METHODS: This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.15 mg/kg times three doses, every 4 hours or a single 8-mg or 32-mg dose followed by two saline doses that began 30 minutes before cisplatin administration. Cisplatin (high-dose > or = 100 mg/m2 or medium-dose 50 to 70 mg/m2) was given as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 hours after cisplatin administration. RESULTS: A total of 699 patients (359 high-dose, 340 medium-dose) were enrolled. Of these, 618 were assessable for efficacy (15 ineligible, 66 protocol deviations). The 32-mg dose was superior to the 8-mg single dose with regard to total number of emetic episodes (high-dose, P = .015; medium-dose, P < .001), complete response (no emetic episodes: high-dose, 48% v 35%; P = .048; medium-dose, 73% v 50%; P = .001) and failure rate (> 5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005). The 32-mg single dose was also superior to the 0.15 mg/kg times three dose regimen with regard to total number of emetic episodes (medium-dose, P = .033) and failure rate (high-dose, 20% v 36%; P = .009; medium-dose, 9% v 22%; P = .011). Ondansetron was well tolerated. The most common adverse event was headache. An approximate 10-fold increase in the incidence of clinically significant transaminase elevations was observed in the high-dose versus medium-dose cisplatin strata (aspartate aminotransferase [AST], 6.5% v 0.7%; serum alanine aminotransferase [ALT], 5.0% v 0.3%). CONCLUSION: A 32-mg single dose of ondansetron is more effective than a single 8 mg dose and is at least as effective as the standard regimen of 0.15 mg/kg times three doses in the prevention of cisplatin-induced acute emesis. PMID- 1453212 TI - Cancer Pain Assessment and Treatment Curriculum Guidelines. The Ad Hoc Committee on Cancer Pain of the American Society of Clinical Oncology. AB - PURPOSE: More than 70% of patients with cancer develop significant pain at some time during the course of their illness. Despite the general consensus that most cancer pain can be treated effectively, many patients receive inadequate treatment of their pain. One significant contributing factor is the failure of health care professionals to receive formal training in this important aspect of oncology. The Cancer Pain Assessment and Treatment Curriculum Guidelines reflect the American Society of Clinical Oncology's commitment to providing optimal pain relief to patients with cancer. These guidelines represent an effort to promote formal instruction on the assessment and treatment of cancer pain in training programs and continuing education courses. DESIGN AND RESULTS: The curriculum is broad in scope and applicable to patients of all ages. The guidelines emphasize the need for (1) routine pain assessment, (2) proficiency in prescribing opioids, nonopioid analgesics, and adjuvant medications, and (3) an understanding of the potential benefits of antineoplastic, anesthetic, neurosurgical, and behavioral approaches, which often require a coordinated multidisciplinary approach. CONCLUSION: This curriculum should prove a valuable guide to those who wish further education on the optimal treatment of cancer pain. PMID- 1453213 TI - Prerequisites for in vivo cell kinetic studies in patients. PMID- 1453214 TI - Suramin: is adaptive control necessary? PMID- 1453215 TI - Hepatic arterial floxuridine infusion and patient survival. PMID- 1453216 TI - Protein kinase C is activated and diacylglycerol is elevated in epidermal cells from Sencar mice fed high fat diets. AB - Studies reported here determined the effect of dietary fat level on membrane phospholipid composition, phosphoinositide labeling, 1,2-sn-diacylglycerol and protein kinase C activity in epidermal cells from female Sencar mice. Animals were fed either high fat (24.6 g/100 g diet) or control (5 g/100 g diet) diets at constant energy intake for 6 to 7 wk or 15 to 22 wk, and epidermal cells were isolated. The level of phosphatidylinositol was significantly lower in the animals fed the control diet than in the animals fed the high fat diet (0.6 vs. 1.2 nmol/10(6) cells). The fatty acid composition of the phospholipids showed significantly lower arachidonic acid level in phosphatidylinositol when the animals were fed the high fat diet. Protein kinase C activity in the solubilized particulate and soluble fraction of the cells was 131 +/- 18% and 62 +/- 14% greater, respectively, in animals fed the high fat diet compared with animals fed control diet. The level of 1,2-sn-diacylglycerol was significantly higher in animals fed the high fat diet (mean nmol/mg lipid +/- SEM: control, 4.5 +/- 0.5; high fat, 7.0 +/- 0.5). Incorporation of [3H]inositol into inositol lipid was not altered by diet. Because protein kinase C and 1,2-sn-diacylglycerol have been implicated in tumor promotion, the increase in protein kinase C activity and the elevation of 1,2-sn-diacylglycerol in cells from animals fed the high fat diet may be important in the high cancer rate observed with these diets. PMID- 1453217 TI - Sweet lupin protein quality in young men. AB - The protein quality of Lupinus albus cv Multolupa was evaluated in young adult males using the nitrogen balance technique at graded levels of N intake, and compared with egg protein. Lupin protein was consumed at levels of 0.4, 0.6 and 0.8 g/(kg.d) and egg protein at 0.3, 0.45 and 0.6 g/(kg.d). Each period started with 1 d of consuming a protein-free diet; the next 6 d were used as adaptation and the last 4 d for balance. The levels of protein intake were randomly assigned by a modified Latin square. Energy intake was individually adjusted. Mean apparent N digestibility values of lupin protein were 78.8, 76.1 and 70.2% for the levels of 0.8, 0.6 and 0.4 g protein(kg.d), respectively, and 83.8, 78.3 and 67.1% for egg protein consumed at levels of 0.6, 0.45 and 0.3 g protein/(kg.d), respectively. The N balance results obtained when subjects consumed lupin were 16.4, 0.2 and -15.1 mg N/(kg.d) for protein intakes of 0.8, 0.6 and 0.4 g/(kg.d), respectively. Those obtained for egg consumption were 12.6, -3.6 and -17.1 mg N/(kg.d) for protein intakes of 0.6, 0.45 and 0.3 g/(kg.d), respectively. The linear regressions of intake and absorbed N to retained N for lupin were: N retained = -43.41 + 0.50 N intake and N retained = -36.30 + 0.53 N absorbed. The corresponding regressions for egg were: N retained = -45.0 + 0.65 N intake and N retained = -30.65 + 0.58 N absorbed. The net protein utilization of lupin was 77% that of egg protein. PMID- 1453218 TI - Alkaline phosphatase activity and pyridoxal phosphate concentrations in the milk of various species. AB - Because pyridoxal phosphate does not normally cross membranes, it was intriguing that the concentration of pyridoxal phosphate is much higher in goat milk than in human milk. We also noted that, although the total vitamin B-6 concentration of bovine milk was similar to that of caprine milk, the bovine milk had lower pyridoxal phosphate. Preliminary data from five Alpine goats, five Brown Swiss cows, five Holstein cows and three humans suggested that there was an inverse relationship between pyridoxal phosphate concentration and phosphatase activity in the goats and cows but not in the humans. This was confirmed with additional data from Nubian goats, Jersey and Guernsey cows, and crossbred sows. Combining the animal data yielded the following relationship between pyridoxal phosphate (PLP, mumol/L) and alkaline phosphatase (P'ase) activity (mmol/(min.L): PLP = 2.03e(-2.26 P'ase) + 0.03. The human milk samples were low in both pyridoxal phosphate and alkaline phosphatase. We conclude that in goats, cows and pigs a significant fraction of the vitamin B-6 appearing in the milk is secreted as pyridoxal phosphate, probably bound to protein, and varying amounts may then be hydrolyzed back to pyridoxal depending on the alkaline phosphatase activity. Human mammary tissue apparently secretes very little pyridoxal phosphate. PMID- 1453219 TI - Comparative metabolism and requirement of vitamin K in chicks and rats. AB - The metabolic basis for the high vitamin K requirement of chicks compared with rats was investigated. When chicks and rats were fed the same diet, containing 500 micrograms phylloquinone/kg, the total amounts of phylloquinone and its epoxide metabolite found in the liver and plasma were similar in both species. However, phylloquinone 2,3-epoxide was present in high concentrations in chick liver and serum but not in rat liver and serum. This metabolite of the vitamin is normally reduced by a hepatic vitamin K epoxide reductase. The activity of this enzyme in chicks was approximately 10% of that in rats, and the inability of chicks to effectively recycle the epoxide of vitamin K seems to be the major factor in its high requirement. Other species differences in vitamin K metabolism were observed. Much higher concentrations of bacterial menaquinones were present in rat feces compared with chick feces, but neither species had appreciable hepatic concentrations of menaquinones. Chicks, but not rats, were found to have a liver concentration of menaquinone-4 that exceeded that of phylloquinone. This vitamer was present even when its recognized precursor, menadione, was not present in the diet, and the data indicate that chicks convert phylloquinone to menaquinone-4 under the conditions of these experiments. The mechanism of this conversion was not established. PMID- 1453220 TI - Neither dietary fructose, dextrose nor starch modifies in vitro glycerol release by adipocytes from streptozotocin-diabetic rats. AB - Because we found previously that fructose feeding could alter lipolytic responses to isoproterenol and insulin in normal rats, we studied the effects of the same diet in neonatal, streptozotocin-diabetic rats. Twenty-seven 5-wk-old diabetic Sprague-Dawley rats were fed a diet containing 57% carbohydrate as either fructose, dextrose or starch for 6 wk. At the end of the nutritional period, plasma glucose and insulin concentrations in fed rats were similar in the three diabetic groups. Plasma triacylglycerol concentrations were higher in the fructose-fed group than in the other two groups (P < 0.05). Neither the maximal adipocyte lipolytic response (fructose = 1147 +/- 165%, starch = 1823 +/- 329% and dextrose = 1287 +/- 239% of basal values) nor the sensitivity to isoproterenol (ED50) was changed by the dietary carbohydrate exchange. The maximal antilipolytic action of insulin (starch = 68 +/- 10%, dextrose = 41 +/- 13%, fructose = 95 +/- 29% of stimulated lipolysis values) was comparable in the three diet groups. Thus, 6 wk of fructose feeding in diabetic rats increased plasma triacylglycerol concentrations, but had no detectable effect on plasma glucose or insulin concentrations, isoproterenol-induced lipolysis or the antilipolytic action of insulin. PMID- 1453221 TI - An extract of Gymnema sylvestre leaves and purified gymnemic acid inhibits glucose-stimulated gastric inhibitory peptide secretion in rats. AB - Gastric inhibitory peptide release into the portal vein in response to duodenal infusion of D-glucose was studied in the presence of a leaf extract of Gymnema sylvestre, purified gymnemic acid and inhibitors of some putative glucose sensors and carriers in the intestinal lumen. Intraduodenal infusion of D-glucose significantly increased the portal immunoreactive gastric inhibitory peptide concentration in a dose-dependent manner. The increase in the portal immunoreactive gastric inhibitory peptide induced by glucose was significantly depressed by concomitantly infused leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin but not by cytochalasin B. Mannoheptulose, which inhibits glycolysis, and procaine and lidocaine, which inhibit the vagal glucoreceptor in the lumen, did not affect portal immunoreactive gastric inhibitory peptide concentrations. These results suggest that a glucose receptor, which interacts with the leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin, exists for the release of immunoreactive gastric inhibitory peptide and that the glucose receptor for gastric inhibitory peptide release is not likely to be identical with a glucose transporter or a vagal glucoreceptor in the lumen. PMID- 1453222 TI - Placental composition does not respond to changes in maternal dietary carbohydrate intake in rats. AB - In this study we investigated whether placental glycogen reserves and protein and DNA content could be manipulated by altering the level of glucose in the maternal diet. Pregnant rat dams were fed isocaloric diets containing graded levels of glucose (0, 12, 24 and 60%), and placentas were analyzed for glycogen, protein and DNA content on gestational days 18.5 to 21.5. Regardless of the level of glucose in the maternal diet, there was a significant increase in placental size with advancing age, which was characterized by protein accretion but not by an increase in cell number of glycogen content. Restriction of glucose in the diets of pregnant dams failed to produce statistically significant reductions in placental protein, DNA and glycogen and did not retard placental growth, even though intrauterine growth retardation was observed. Fetal weight, plasma glucose, and liver and heart glycogen were positively correlated with placental weight and inversely correlated with placental glycogen and DNA concentrations; by contrast, no significant correlations were calculated between maternal and placental variables. Our study indicates that the placenta is not affected by a specific dietary glucose restriction and that changes in placental weight or glycogen content do not account for the growth retardation observed in fetuses of dams fed glucose-restricted diets. PMID- 1453223 TI - Prevention of immunologic stress contributes to the growth-permitting ability of dietary antibiotics in chicks. AB - The growth-permitting ability of antibiotics fed to broiler chicks was studied as it relates to the state of activation of the immune system. In Experiment 1, chicks were fed two levels of antibiotics (0 or 100 mg streptomycin + 100 mg penicillin/kg diet) and were raised either in an environment with poor sanitation to create a chronic immune stress or in a clean environment. Chicks raised in the unsanitary environment and not fed antibiotics had significantly lower (P < 0.05) rates of weight gain and efficiencies of feed utilization, and higher levels of plasma interleukin-1, compared with chicks raised in the clean environment or chicks raised in the unsanitary environment and fed antibiotics. Adding antibiotics to the diet of birds in the clean environment did not affect any variable. In Experiment 2, chicks were raised in a conventional environment and fed two levels of an antibiotic (0 or 100 mg tetracycline/kg diet). After a 15-d feeding period, half of the chicks were injected with Salmonella typhimurium lipopolysaccharide to create an acute immunologic stress. Feeding antibiotic resulted in improved weight gain, feed consumption and efficiency of feed utilization. Lipopolysaccharide-injected birds developed heavier livers, spleens and intestines relative to body weights and higher rectal temperatures and hepatic metallothionein concentrations, presumably due to an immunologic stress. Omitting antibiotic from the diet resulted in similar changes. These results indicate that feeding antibiotics may permit growth by preventing immunologic stress and associated metabolic changes brought about by monokines including interleukin-1. PMID- 1453224 TI - Dietary guar gum halts further renal enlargement in rats with established diabetes. AB - Guar gum, a dietary fiber known to improve glucose tolerance, was fed to rats with established diabetes to determine its effect on renal enlargement and microalbuminuria. Diabetic rats were fed a modified AIN-76A (basal) diet for 4 wk, at which time half the rats continued to receive the same basal diet (DB-BA group) and half were switched to a 5% guar gum diet (DB-GG group). Nondiabetic rats fed the basal diet served as controls (NRL group). After 8 additional weeks the animals were killed. Glycated hemoglobin, a measure of long-term blood glucose control, was 14.4% in the DB-BA group and 12.4% in the DB-GG group, a statistically significant difference (P < 0.05). Kidney weight of the DB-BA group (3.51 g) was significantly greater than that of the DB-GG group (2.76 g) (P < 0.05). Eight weeks after induction of diabetes, 24-h urinary albumin excretion was highest in the DB-BA group and lowest in the NRL group; excretion in the DB GG group (4 wk of guar feeding) was intermediate. However, by 12 wk no differences in albumin excretion among the groups were apparent. These results suggest that guar gum may be useful for slowing the progression of diabetic nephropathy and that guar gum deserves further study in this regard. PMID- 1453225 TI - Phenylalanine flooding dose procedure is effective in measuring intestinal and liver protein synthesis in sheep. AB - We conducted two experiments to evaluate the flooding dose method for measuring intestinal and liver protein synthesis in sheep. Experiment 1 showed that large doses of phenylalanine did not cause marked metabolic disturbances. Experiment 2 examined the effectiveness of flooding with phenylalanine and the time dependency of the protein synthesis calculation. Rams were injected with 1.2 MBq L-[ring 2,6 3H]phenylalanine/kg body wt and slaughtered 20, 40 or 60 min later. Plasma specific radioactivity reached a plateau within 2.5 min and did not change significantly (P > 0.05) throughout the experiment. Tissue intracellular free pool specific radioactivity also remained constant from 20 to 60 min postinfusion. Flooding conditions were achieved in the intracellular free pool of intestinal tissues (specific radioactivity 70-96% of plasma specific radioactivity), although liver flooding was less successful (57-67%). Protein synthesis rates measured after 20 min were significantly (P < 0.05) higher in the liver, jejunum and ileum than those measured at 60 min. Protein synthesis rates also tended to decline with time in the duodenum and colon (P > 0.05). There were no significant differences (P > 0.05) between protein synthesis rates calculated using the intracellular specific radioactivity vs. plasma specific radioactivity in the duodenum, ileum or colon. Therefore, this method represents an improvement over continuous infusion methods for measurements of protein synthesis in visceral tissues. PMID- 1453226 TI - Erythrocyte metallothionein response to dietary zinc in humans. AB - The response of erythrocyte metallothionein to dietary zinc in human subjects was evaluated in a controlled metabolic protocol including standard indices of zinc status. Fifteen male subjects, age 27 +/- 3.6 y, participated in a 90-d, four phase study consisting of acclimation (7 d; 15 mg Zn/d), treatment (6 wk; either 3.2, 7.2 or 15.2 mg Zn/d), depletion (12 d; 0.55 mg Zn/d) and supplementation (30 d; self-selected diet plus 50 mg Zn/d) phases. During the treatment phase erythrocyte metallothionein decreased in the group fed 3.2 mg Zn/d. Erythrocyte metallothionein decreased during the depletion phase (46 +/- 10%) to below the normal concentration in all groups and increased in the supplementation phase. Plasma zinc concentration decreased in the group fed 3.2 mg Zn/d during the treatment phase relative to the acclimation phase. Erythrocyte zinc decreased in all groups during the depletion phase relative to the treatment phase, and then increased during the supplementation phase. These data suggest that erythrocyte metallothionein can be used as a measure of status in severe zinc depletion and that comparing the change in erythrocyte metallothionein over a 6-wk period can differentiate between low and adequate levels of dietary zinc intake. PMID- 1453227 TI - 5-Methyltetrahydrofolate is reabsorbed and metabolized in isolated perfused rat kidney. AB - The renal regulation of folate excretion is an important component in maintaining the body burden of folate. The tubular processes for folate disposition have been examined by a variety of methods to elucidate the mechanism by which renal folate excretion is regulated. Accordingly, the isolated perfused rat kidney technique was evaluated by investigating the clearance and metabolic patterns of 5 methyltetrahydrofolate (5-CH3-H4PteGlu). Kidneys from male Sprague-Dawley rats were perfused in vitro with [3H]5-CH3-H4PteGlu (1-2000 nmol/L). Linear regression analysis of 5-CH3-H4PteGlu excretion vs. filtered load revealed a tubular transport maximum of 7.5 pmol x min-1.g-1. A dual component system for tubular transport of 5-CH3-H4PteGlu was found: a high capacity, nonsaturable system and a low capacity, saturable system represented by the transport maximum. Furthermore, HPLC analysis of urine demonstrated renal uptake and metabolism of the labeled tracer. Tetrahydrofolate was identified as one metabolic product that indicated secretion of this compound. Additional metabolites were identified from kidney samples. Results suggest that 5-CH3-H4PteGlu undergoes net reabsorption by a dual component transport system; some of the reabsorbed 5-CH3-H4PteGlu is metabolized to other products that may be secreted in the urine. PMID- 1453228 TI - Intestinal amino acid and monosaccharide transport in suckling pigs fed milk replacers with different sources of carbohydrate. AB - Omnivorous mammals are able to adaptively modulate rates of intestinal nutrient transport to match changes in diet. Because adaptive responses during suckling, when dietary composition is relatively constant, have not been adequately determined, we measured in vitro sugar and amino acid uptake [nmol/(mg tissue.min)] in suckling pigs fed milk replacers with either lactose (LAC) or a 60:40 mixture of maltodextrin and sucrose (MDS). The MDS-fed pigs initially grew slower, but had intestinal dimensions similar to those of LAC-fed siblings when normalized to body weight. Carrier-mediated uptake for three monosaccharides (glucose, galactose, fructose) did not differ between LAC- and MDS-fed pigs at 5, 10, 15 and 20 d of age. Interdiet differences in rates of leucine and proline uptake, despite identical types and concentration of protein in both milk replacers, are indicative of non-specific responses to diet during suckling. Uptake capacities (grams of monosaccharide absorbed per 24 h) never exceeded estimates of monosaccharide intake by more than fourfold and were less than aldohexose intake during early suckling. Our results indicate 1) age-related changes in rates of nutrient uptake are genetically programmed and little influenced by diet; 2) any responses to diet are nonspecific and likely involve a shift in the timing of the genetic program; and 3) at birth and throughout suckling, pigs are capable of absorbing limited quantities of alternative nutrients. PMID- 1453229 TI - Sesame seed lignans and gamma-tocopherol act synergistically to produce vitamin E activity in rats. AB - Vitamin E activity of sesame seed, which contains only gamma-tocopherol, a compound that has vitamin E activity equal to only 6-16% that of alpha tocopherol, was examined in two experiments. In the first experiment, groups of rats were fed four diets: vitamin E-free control diet, alpha-tocopherol containing diet, gamma-tocopherol-containing diet and sesame seed-containing diet. Changes in red blood cell hemolysis, plasma pyruvate kinase activity, and peroxides in plasma and liver, as indices of vitamin E activity, were examined. The sesame seed diet has high vitamin E activity, whereas this activity was low in the gamma-tocopherol diet. In plasma and liver, alpha-tocopherol was found in high concentration only in the alpha-tocopherol-fed group, and gamma-tocopherol was found in high concentration only in the sesame seed-fed group, with negligible amounts of gamma-tocopherol in liver of the gamma-tocopherol-fed group. In the second experiment, two diets containing sesame lignan (sesaminol or sesamin) and gamma-tocopherol were tested. Results in both of the sesame lignan fed groups were comparable to those observed in the sesame seed-fed group in Experiment 1. These experiments indicate that gamma-tocopherol in sesame seed exerts vitamin E activity equal to that of alpha-tocopherol through a synergistic interaction with sesame seed lignans. PMID- 1453230 TI - Soluble wheat pentosans exhibit different anti-nutritive activities in intact and cecectomized broiler chickens. AB - The role of the ceca in the anti-nutritive effect of wheat pentosans was studied in intact and cectomized broiler chickens. Addition of wheat pentosans (equivalent to 30 g pure arabinoxylans/kg diet) depressed the digestibilities of starch, protein and fatty acids in both types of birds. Cecectomized birds were less efficient (P < 0.01) in dry matter and energy utilization, but starch digestion was not influenced by cecectomy. Inclusion of isolated wheat pentosans decreased the fecal protein digestibility by 18% in intact birds and by 7% in cecectomized chickens, with the bird type x pentosan interaction being significant (P < 0.05). The ileal pentosan digestibility was not affected either by addition of isolated pentosans or by cecectomy; however, the fecal pentosan digestibility was significantly (P < 0.001) influenced. Thus, in intact birds the fecal pentosan digestibility coefficient was 0.216 in birds fed the control diet and 0.646 in those fed the diet with wheat pentosans; in cecectomized chickens the corresponding values were 0.193 and 0.399, indicating a significant influence of the hindgut microflora on pentosan digestion. The ileal and fecal digestibilities of fatty acids were also determined. There was no interaction between bird type and pentosan addition in the ileal digestibilities of fatty acids. Depressions in the fecal digestibilities of fatty acids 14:0 and 18:0 were significantly (P < 0.05) greater in intact birds. Our results indicate that anti nutritive effects of wheat pentosans in poultry are partially due to an increased activity of hindgut microflora. PMID- 1453231 TI - Reduction of phytic acid in soybean products improves zinc bioavailability in rats. AB - The inhibitory effect of phytic acid in soybean products on zinc bioavailability was evaluated in two experiments in rats. In Experiment 1, soybean flours containing different natural phytic acid levels produced by sand culture techniques that limited phosphorus during growth of the soybean plants were formulated into diets. The rats fed a higher phytic acid level diet had lower food intake, depressed weight gain, and lower tibia zinc gain (P < 0.05). A negative, linear relationship between tibia zinc gain and dietary phytic acid level was found. In Experiment 2, two commercially produced soybean isolates containing either normal phytic acid level or a reduced level were formulated into diets. Slope ratio analysis revealed that relative zinc bioavailability from phytic acid-containing soybean isolate-based diets was significantly reduced (P < 0.05) compared with control diets. Reduced phytic acid soybean isolate-containing diets resulted in a significant increase of zinc bioavailability compared with normal phytic acid diets (P < 0.01). These results coupled with other reports indicate that phytic acid is the primary inhibitory factor in soybean products that results in reduced zinc bioavailability and that phytate reduction in soybean protein increases zinc bioavailability. PMID- 1453232 TI - Estimation of the dietary riboflavin required to maximize tissue riboflavin concentration in juvenile shrimp (Penaeus monodon). AB - The riboflavin requirements of marine shrimp (Penaeus monodon) were evaluated in a 15-wk feeding trial. Juvenile shrimp (initial mean weight, 0.13 +/- 0.05 g) were fed purified diets containing seven levels (0, 8, 12, 16, 20, 40 and 80 mg/kg diet) of supplemental riboflavin. There were no significant differences in weight gains, feed efficiency ratios and survival of shrimp over the dietary riboflavin range. The riboflavin concentrations in shrimp bodies increased with the increasing vitamin supplementation. Hemolymph (blood) glutathione reductase activity coefficient was not a sensitive and specific indicator of riboflavin status of the shrimp. The dietary riboflavin level required for P. monodon was found to be 22.3 mg/kg diet, based on the broken-line model analysis of body riboflavin concentrations. Shrimp fed unsupplemented diet (riboflavin concentration of 0.48 mg/kg diet) for 15 wk showed signs of deficiency: light coloration, irritability, protuberant cuticle at intersomites and short-head dwarfism. PMID- 1453233 TI - Absorption and metabolism of pyridoxamine in mice. II. Transformation of pyridoxamine to pyridoxal in intestinal tissues. AB - The absorption of pyridoxamine from the intestine of the mouse was studied in whole animals. [3H]Pyridoxamine was orally administered and the distribution of isotope between the six recognized forms of vitamin B6 was determined in portal blood after the administration. When small doses (1.4 or 14 nmol) were administered, labeled pyridoxamine could hardly be found in the portal blood, although labeled pyridoxal and pyridoxal phosphate were found in the same blood. However, when a large amount (46 or 140 nmol) was given, a significant amount of labeled pyridoxamine was found with labeled pyridoxal and pyridoxal phosphate in the portal blood. These results suggest that a physiological dose of pyridoxamine is rapidly transformed to pyridoxal in the intestinal tissues and then released in the form of pyridoxal into the portal blood. PMID- 1453234 TI - Vitamin C activity of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid in guinea pigs. AB - The vitamin C activity of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), which is one of chemically stable derivatives of L-ascorbic acid (AsA), in guinea pigs was investigated. Male guinea pigs were divided into 9 groups and fed AsA deficient diet for 24 days with the following supplement: AA-2G- or AsA supplemented groups were orally supplemented with 0.96, 1.92, 9.6 and 192 AA-2G mg/animal/day or equimolar amounts of AsA (0.5, 1, 5 and 100 mg/animal/day, respectively); AsA-deficient group received neither of them. The body weight gain, serum alkaline phosphatase activity, and the concentration of AsA and AA-2G in the liver, adrenals and urine of the guinea pigs were measured at the end of the experimental period. The AA-2G-supplemented guinea pigs showed similar body weight gain to the animals supplemented with equimolar amount of AsA. Serum alkaline phosphatase activity in both AA-2G- and AsA-supplemented groups was significantly higher than that of AsA-deficient group. But there was no significant difference between the groups supplemented with AA-2G and the equimolar amount of AsA. AA-2G-supplemented guinea pigs showed no apparent symptoms of scurvy. In AA-2G-supplemented groups, AA-2G was not detected in the liver, adrenals and urine, but AsA was found and the AsA concentration increased with increasing AA-2G dosage. The AsA concentration in the tissues of each AA-2G supplemented groups was higher than that of AsA-deficient group, which was similar to that of the groups supplemented with equimolar amount of AsA. These results showed that AA-2G has the same vitamin C activity as AsA on a molar basis for the orally supplemented guinea pigs. PMID- 1453235 TI - Comparative effect of casein and soybean protein isolate on body fat accumulation in adult rats. AB - The effect of dietary protein on the body fat accumulation was studied in rats. Adult rats weighing about 300 g were fed 21% protein (casein or soybean protein isolate) and 5% oil diets by pair-feeding for 65 days in Experiment 1. In Experiment 2, only protein and oil contents were changed, 25 and 10%, respectively. Final body weights of the two dietary groups were similar in both experiments, especially in Experiment 2. Total body fat was slightly lower in the soybean protein diet group than in the casein diet group in Experiment 2, only when it was expressed as the percentage against body weight. However, intra abdominal fat was significantly lower in the soybean protein diet groups than in the casein diet groups in both experiments. Serum lipid levels were greatly lower in the soybean protein diet group than in the casein diet group in Experiment 2 (the data were not available in Experiment 1). The results suggest that dietary soybean protein has the effect to lower the intra-abdominal fat accumulation as compared with casein. PMID- 1453236 TI - Effects of dexamethasone on experimental atherosclerosis in cholesterol-fed rabbits. AB - We studied the effects of a synthetic adrenocortical steroid, dexamethasone, on the development of experimental atherosclerosis in cholesterol-fed rabbits. Daily intramuscular injection of dexamethasone (0.125 mg/day) remarkably inhibited the aortic atherosclerosis induced by feeding a 1% cholesterol-rich diet for 8 weeks, although it aggravated diet-induced hyperlipidemia. Histologically, less foam cell accumulation was observed in the atherosclerotic lesions of the dexamethasone-treated rabbits as compared with the control animals. When rabbits were fed a normal chow diet for 10 weeks after receiving the 1% cholesterol-rich diet for 8 weeks, no regression of atherosclerotic lesions was observed with the daily injection of dexamethasone (0.125 mg/day); however, the drug again tended to inhibit further progression of atherosclerosis. The anti-atherogenic mechanism of dexamethasone may involve an inhibition of recruitment of blood monocytes and the insudation of atherogenic lipoproteins, mainly beta-very low density lipoprotein (beta-VLDL) in the present experiments, into the aortic intima, or it may involve a change in the size and structure of the lipoproteins, resulting in their decreased passage through the aortic endothelium into the intima. PMID- 1453237 TI - Diurnal variation and increase of disaccharidase activity in diabetic rats. AB - The small intestinal disaccharidase activity and its daily variation in the diabetic rat have not been well described. Therefore, the small intestinal disaccharidase (maltase, lactase and sucrase) activity and its daily profile were studied in streptozotocin-induced diabetic rats under physiological conditions. In diabetic rats, a similar pattern of diurnal variation of disaccharidase activity to control rats was observed, while the relationships between daily change of disaccharidase activity and that of food consumption suggested that there was a different mechanism of diurnal variation in diabetic rats. On the other hand, a significant increase of mean 24-h lactase and sucrase activities was noted in diabetic rats, while that of maltase was not significant. Using the in vitro incubation method, a significant correlation between glucose concentration and lactase or sucrase activity but not maltase activity was observed. However, insulin showed no effect on disaccharidase activity. Thus we clarified the presence of a diurnal variation of disaccharidase activity and an increase in its activity in diabetic rats. This change was suggested to be derived from high plasma glucose level. PMID- 1453238 TI - Effect of maltitol intake on intestinal calcium absorption in the rat. AB - To examine whether sugar alcohol affects intestinal calcium absorption, 5-week old male Wistar rats were fed a basal diet (66% starch) or the diets containing either 10% maltitol, 10% sorbitol or 10% lactose. At 2 and 6 weeks after the start of feeding, the animals were subjected to 5-day-period calcium balance study. Feeding maltitol diets as well as sorbitol diet led to a significantly elevated intestinal calcium absorption and calcium retention. Lactose diet did not produce an increased intestinal calcium absorption in the condition used in the present study. To explore whether maltitol can exert its effect in a short period of time, the rats were starved for 16h and were fed by a polyethylene tube the diet containing 0.44% calcium together with either 10% maltitol or 10% glucose. The total calcium remaining in the gastrointestinal tract at 6h after feeding was significantly decreased in the rats given maltitol diet as compared to the rats given glucose diet. When 10 microCi of 45CaCl2 was given orally with the diets containing maltitol or glucose, the amount of 45Ca remaining in the gastrointestinal tract at 6h after its administration was smaller in the rats fed maltitol diet than in the rats fed glucose diet. These results suggest that both di- and monosaccharide alcohols might affect intestinal epithelium, resulting in an enhanced intestinal calcium absorption. PMID- 1453239 TI - Qualitative and quantitative estimation of soluble indigestible polysaccharides as substrate for hindgut fermentation by mini-scale batch culture. AB - Pectin, guar gum, transgalactosylated oligosaccharide and glucose were estimated as substrate for hindgut fermentation by measuring the volume of gas released from a 1 ml scale batch culture using rat cecal contents. The amount of short chain fatty acids (SCFA) in cultures of glucose and pectin was also measured. The amount of SCFA (Y mumol/culture) or volume of gas released (Y ml/culture) was expressed as an exponential function of incubation time (t) (Y = A+B x (1-e-kt); A, B and k are constants). The amount of potential production of gas and SCFA (B) for glucose was higher than that for pectin and the rate constant of gas and SCFA (k) for pectin was higher than that for glucose. The volume of gas released (ml/culture) correlated positively and linearly with the amount of total SCFA (acetic, propionic and n-butyric acids, mumol/culture). A single regression stood for both glucose and pectin. The gas release followed saturation kinetics. The half maximal concentration and maximal velocity for gas release from pectin were higher than those from other substrates (glucose, guar gum and transgalactosylated oligosaccharide). PMID- 1453240 TI - Detection of injury-prone behaviors among internal medicine patients. AB - OBJECTIVES: 1) To describe the prevalence of eight injury-prone behaviors (IPBs) and the associations of these behaviors with ten standard chronic disease and sociodemographic risk factors (CDSRFs) among internal medicine patients and 2) to identify a subset of patients with multiple IPBs who might be at particularly high risk of injury. DESIGN: Cross-sectional survey. SETTING: The University of Colorado Health Sciences Center general internal medicine clinic. PATIENTS: Four hundred ninety-two consecutive continuity care patients were eligible. The response rate was 94.3% (464/492). INSTRUMENT: A validated, self-administered questionnaire. MAIN RESULTS: Thirty-four percent of patients did not wear safety belts regularly and 32% had no smoke detector in their homes. Nearly 26% of patients had firearms at home and 6% had a loaded and unlocked gun at home. Fourteen percent of patients had seriously thought about suicide and 6% had attempted suicide. In the prior month, 10% had ridden with a drunk driver, and 4% had driven after drinking too much. Of patients aged 65 years or older, 50% had had recent falls. After adjustment for other CDSRFs, problem drinking was the CDSRF most frequently associated with IPBs. Among men, problem drinking was significantly associated with drinking and driving (OR = 35.3), safety belt non use (OR = 4.3), and previous thoughts of or attempts at suicide (OR = 6.2). Among women, problem drinking was significantly associated with drinking and driving (OR = 8.7). Among men, being unmarried was the demographic risk factor associated with the most IPBs. Of all IPBs, safety belt non-use was most frequently associated with CDSRFs (ORs ranged from 2.8 to 4.4). Men with three or more IPBs were more likely to be problem drinkers (OR = 9.6), smokers (OR = 15.8), obese (OR = 6.3), and unmarried (OR = 67.1). CONCLUSIONS: 1) Injury-prone behaviors are common among patients attending a university-based internal medicine clinic; 2) men and women have substantially different patterns of risk factor associations; 3) CDSRFs, such as problem drinking smoking, and being unmarried, are associated with many IPBs; 4) safety belt non-use is the IPB associated with the most CDSRFs; and 5) CDSRFs appear to cluster in men with multiple IPBs, suggesting that screening for high-risk individuals may be feasible in clinical practice. PMID- 1453241 TI - Driving and Alzheimer's disease. AB - OBJECTIVE: To examine the driving status of Alzheimer's disease (AD) patients presenting to a geriatric clinic, and to investigate the ability of brief cognitive assessment measures to identify those who are no longer able to continue driving safely. DESIGN: Based on caregivers' reports of driving status, AD patients were divided into three groups: those who were still driving with no difficulty, those still driving but having difficulty, and those who had stopped driving due to their cognitive problems. Scores on commonly used cognitive tests were compared across groups. Age, gender, and duration of dementia were also investigated. SETTING: The University of Washington Medical Center (UWMC) outpatient Geriatric and Family Services Clinic. PARTICIPANTS: One hundred consecutive patients who met DSM-III-R criteria for primary degenerative dementia and were either currently driving or had stopped driving due to cognitive deficits. MEASUREMENT AND MAIN RESULTS: Twenty-two subjects were reportedly still driving with no difficulty, 23 were still driving with difficulty, and 55 were no longer driving. Both mental status screening and functional assessments were significantly different between drivers and nondrivers, as were scores on a visual-spatial task. In addition, gender and age distinguished the groups: younger drivers and men drivers were less likely to stop driving despite significant cognitive impairment. CONCLUSIONS: Given the large number of AD patients who continue to drive and who experience problems with driving, this investigation highlights the need for assessment of driving safety as part of a clinical dementia evaluation. In addition, the results suggest a combination of cognitive and functional measures that may be helpful in identifying patients who are at greatest risk for unsafe driving. PMID- 1453242 TI - Long-term success with the national health objective for influenza vaccination: an institution-wide model. AB - PURPOSE: To assess the long-term effectiveness of an influenza vaccination program. SETTING: 725-bed university-affiliated VA teaching hospital providing care to over 35,000 outpatients. DESIGN AND SUBJECTS: 500 randomly selected outpatients were surveyed following each immunization season using a validated, self-administered, postcard questionnaire. PROGRAM DESCRIPTION: The institution wide program, designed to function automatically and to be independent of physician initiative, emphasizes organizational and patient-oriented educational strategies: 1) a hospital policy allowing nurses to vaccinate without a physician's order; 2) a walk-in flu shot clinic; 3) reminders on clinic progress notes; and 4) an educational mailing to all outpatients. The program was initiated in 1987 and has been maintained for each subsequent immunization season. RESULTS: The response rate was over 75% for each of the four years in which there were two mailings. The response rate for 1988-1989, in which there were three mailings, was over 85%. Approximately 70% of the respondents were at high risk for influenza and its complications. Vaccination rates for these high risk outpatients have been sustained at over 58% for each immunization season. The program is well received by the hospital staff and now functions on autopilot each year. CONCLUSION: This highly successful institution-wide influenza vaccination program can be sustained long-term. Elements of this program may help others take advantage of opportunities for influenza prevention. PMID- 1453243 TI - Demographic differences in health status of homeless adults. AB - OBJECTIVE: To determine how the physical health of homeless adults varies by the demographic characteristics of age, gender, ethnicity, lifetime length of homelessness, and work status. PARTICIPANTS: A community-based sample of 529 homeless adults. STUDY DESIGN: In multivariate analyses, the authors studied the independent contributions of five demographic groups to variations in 12 physical health measures (based on self-reports from face-to-face interviews, screening physical examinations, and venous blood samples). MEASUREMENTS AND MAIN RESULTS: Older persons were more likely to have a functional disability (p < 0.001), chronic disease (p < 0.001), and greater risk of dying (p < 0.001), but less likely to abuse substances (p < 0.001). Men were more likely than women to be substance users (p < 0.001) and to have a greater risk of dying (p < 0.001). Whites and blacks were less likely than respondents in other ethnic groups to have an abnormal blood test (p < 0.001). Persons homeless longer were more likely to be substance users (p < 0.001) and to have experienced trauma (p < 0.001). Working for pay was not related to any of our health measures. CONCLUSIONS: Age and gender contributed most to the understanding of differences in health status among homeless adults. Since the homeless have a wide variety of physical, mental, social, and substance-abuse problems, primary care providers are in the best position to provide the broad-based care needed by such persons. PMID- 1453244 TI - Patient characteristics related to intensity of weight reduction care in a university medical clinic. AB - OBJECTIVE: To identify patient characteristics related to intensity of weight reduction care provided in a primary care practice. DESIGN: Cross-sectional study linking data from a patient survey and data from medical records. SETTING: Internal medicine housestaff clinic in an urban university hospital. PARTICIPANTS: 321 outpatients who represented a systematic sample of all outpatients who had visited the clinic over one year. MEASUREMENTS AND MAIN RESULTS: The patient population was largely black (86%) and female (65%). Most patients (54%) were overweight [body-mass index (BMI) > 85th percentile for the United States by gender]. Intensity of care was defined by a composite scale: points were awarded for actions documented in the medical chart or recalled by the patient. Factors independently associated with a higher intensity of care among the 161 overweight patients were: BMI [odds ratio (OR) = 1.13 per kg/m2; 95% confidence interval (95% CI) = 1.04, 122; p = 0.002], the patient's self perception of being overweight (OR = 5.37; 95% CI = 1.99, 14.46; p = 0.001), and age of 64 years or younger (OR = 2.48; 95% CI = 1.12, 5.48; p = 0.02). Race, gender, and presence of hypertension or hypercholesterolemia were not associated with greater intensity of care. CONCLUSIONS: Patients with hypertension and hypercholesterolemia may be receiving suboptimal weight reduction care. Heightened awareness of being overweight may enhance the provision of weight reduction care. Prospective studies are required to confirm these findings. PMID- 1453245 TI - Health behavior changes in the United States, the United Kingdom, and France. AB - OBJECTIVE: To determine changes in health behaviors in the United States, the United Kingdom, and France over the previous two years. DESIGN: Cross-sectional survey of nationally representative samples. SETTING/PARTICIPANTS: Surveys conducted between June and November 1988 on persons aged 16 to 50 years in the United States (n = 1,940), the United Kingdom (n = 1,833), and France (n = 2,294) regarding health behaviors, attitudes toward health, and changes in health practices during the previous two years. MEASUREMENTS AND MAIN RESULTS: Using Bonferroni's adjustment for multiple comparisons, residents of the United States had significantly (p < 0.05) higher Quetelet indices and reported higher egg and red meat consumption, but had lower alcohol consumption, than did residents of either the United Kingdom or France. Americans were also significantly more likely to report attitudes accepting personal responsibility for their health and much more often endorsed the role of health behaviors (e.g., exercise) for decreasing the risk of cardiovascular disease. Changes in health behavior over two years were consistently more likely in the United States for weight loss, decreased alcohol consumption, decreased red meat and egg consumption, and increased exercise. Americans were also much more likely to have changed at least three health behaviors in the previous two years (United States 41.5%, United Kingdom 25.5%, France 13.8%, p < 0.002). A multivariate linear model confirmed the high likelihood of health behavior changes in the United States compared with the United Kingdom or France. CONCLUSIONS: The findings confirm that changes in health behaviors are continuing to occur in the United States, but remain comparatively modest in the United Kingdom and France. These international variations in health behaviors parallel differential declines in mortality rates in ischemic heart disease. PMID- 1453246 TI - The unit of analysis error in studies about physicians' patient care behavior. AB - OBJECTIVE: To estimate the frequency with which patients are incorrectly used as the unit of analysis among statistical calculations in published studies of physicians' patient care behavior. DESIGN: Retrospective review of studies published during 1980-1990. ARTICLES: 54 articles retrieved by a computerized search using medical subject headings for physicians and study characteristics. Article selection criteria included the requirement that the physician should have been the correct unit of analysis. INTERVENTION: Presence of the error was determined by consensus using published criteria. MAIN RESULTS: The error was present in 38 articles (70%). The number of study physicians was reported in 35 articles (65%). The error was found in 57% of articles that reported the number of study physicians and in 95% of those that did not. The error rate was not lower among articles published more recently nor among those published in journals with higher rates of article citations in the medical literature. CONCLUSION: The unit of analysis error occurs frequently and can generate artificially low p values. Failure to report the number of study physicians can be a clue that this type of error has been made. PMID- 1453247 TI - What's preventing more prevention? Barriers to development at academic medical centers. AB - OBJECTIVE: To determine the views of leaders in academic medicine concerning the need for programs in preventive medicine (PM) and the prevailing barriers to program development. DESIGN: Structured interviews. SETTING: Medical schools of the United States. PATIENTS/PARTICIPANTS: 90% of deans and chairpersons of departments of medicine and preventive medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: 91% considered academic PM underdeveloped and 100% considered their own programs average or worse. Identified barriers to development included funding constraints, academic partiality to biomedicine, inadequate quality of preventive medicine research and faculty, public preferences for technologic care, and organization of academic medical centers (AMCs). While 80% perceived a shortage of able PM faculty and 60% considered PM research quality to be inadequate, only 12% of PM units gave research training high priority. While 95% of respondents held that AMCs should develop community programs and 75% identified social problems as a cause of chronic diseases, 65% agreed that community programs are not considered scholarly. Only 23% of PM units gave community service high priority. CONCLUSIONS: A policy contradiction exists: academic leadership agreed on the problems and needed changes in PM, yet the problems were often attributed to nonacademic sources, particularly finding and public preferences, and current academic practices commonly fail to address recognized developmental barriers within academic institutions. A chain of barriers is apparent. Breaking the chain may require a change in our understanding of the role of prevention. PMID- 1453248 TI - Internal medicine training in ambulatory gynecology. AB - OBJECTIVE: To assess internists' perceptions of their training in the management of common problems in ambulatory gynecology and to compare these perceptions with their clinical practice experiences. METHODS: We surveyed 325 internists in the Portland, Oregon, metropolitan area about their residency training and practice experiences in the diagnosis and management of 25 clinical problems in ambulatory gynecology and five nongynecologic problems. RESULTS: Responses were received from 159 internists (48.5%). Overall, the internists reported relatively little residency training in the management of many common gynecologic disorders. Women internists managed gynecologic problems more than did their male counterparts, independent of the number of women patients in their practices. CONCLUSIONS: Internal medicine residency programs need to expand training in ambulatory gynecology to better prepare graduates for clinical practice. PMID- 1453249 TI - Indeterminate HIV-1 western blots: implications and considerations for widespread HIV testing. PMID- 1453250 TI - An observational study of attending rounds. AB - The authors conducted an observational study of attending rounds to determine the current status of this form of clinical teaching in a university-based internal medicine department. Using two forms of measurement, questionnaires and timed observations, we found that 63% of attending physician time was spent in the conference room, 26% in hallways, and only 11% at the bedside. Significant differences were found between estimated and actual times, particularly in discussing previously admitted patients, patient interactions, data reviews, topic presentations, and the category of "other" activities. These results provide a framework for appraising attending rounds and identifying areas that may be improved with a teaching workshop intervention. PMID- 1453251 TI - Halitosis, or the meaning of bad breath. PMID- 1453253 TI - Internal medicine training and women's health: politics and Pap tests. PMID- 1453252 TI - Physicians and AIDS: sexual risk assessment of patients and willingness to treat HIV-infected patients. PMID- 1453254 TI - Coping with government regulations. PMID- 1453255 TI - Sex differences in signs and symptoms from masticatory and other muscles in 19 year-old individuals. AB - Pain and tenderness of masticatory muscles are often related to muscle tenderness elsewhere in the body. It has been shown that women are more prone to musculoskeletal disorders than men. We sought to determine whether sex differences of muscular symptoms were established by the age of 19. The subjects comprised 51 boys and girls who received a questionnaire regarding the function of their masticatory system, frequency of headache, and neck, shoulder and low back pain. Their masticatory system was examined, and neck and shoulders were palpated. For all variables in the questionnaire girls reported symptoms more often than the boys. Of the subjects 50% had tender chewing muscles upon palpation. Again the girls had the most. There was good correlation between reports of pain in one area as compared to others. The number of clinically tender neck and shoulder muscles correlated with the number of tender masticatory muscles. It was concluded that girls presented more muscular symptoms than boys. PMID- 1453256 TI - Complete mandibular denture stability when posterior teeth are placed over a basal tissue incline. AB - Six patients with previous denture experience were provided with new dentures. Metal indicators were placed on either side of the mandibular denture and a cobalt-chromium alloy marker was inserted in the left bucco-posterior area of the mandible in each case. In the new dentures posterior teeth were positioned up to the retro-molar pad, over the basal tissue slope of the posterior mandibular alveolar ridge. After habituation had taken place, a cineradiographic recording was made of chewing. Prior to the second recording the mandibular teeth were removed to a point where the remaining teeth were not over inclined residual alveolar ridges. Denture movement was observed by measuring the distances between the markers on an analytical projector. The results show a significant difference between the cranial values of the two chewing experiences. Values for all denture movements were less after removal of the teeth over an incline. These results support the clinical observation that teeth placed over a basal tissue incline have a destabilizing effect during complete mandibular denture function. PMID- 1453257 TI - Discrimination of clenches at varied jaw positions using autoregressive model coefficients of myoelectrical activities of anterior temporal and masseter muscles. AB - During 10% maximum clenching at intercuspal, protruded, retruded contact and lateral positions, the surface electromyograms (EMG) of bilateral anterior temporal and masseter muscles of 20 normal subjects with intact natural dentitions were recorded. The autoregressive (AR) model of the sampled EMG was then built and the obtained coefficients of the AR model were accepted as featured parameters of the EMG. Finally Bayes' stepwise discriminant analysis was used for establishing discriminant functions of estimating low level clenches at varied jaw positions. It was found that total conformation rates of internal and external sample substitution (15 and 5 subjects) were 82.67% and 78% respectively; the discriminant effect between intercuspal and retruded contact position was not up to predicted standard. The results indicate that AR model coefficients may describe the characteristics of surface EMG of masticatory muscles and easily be used in multiple statistical analysis, from which the classification and diagnosis may be taken. PMID- 1453258 TI - Microleakage of indirect inlays placed on different kinds of glass ionomer cement linings. AB - The objective of this study is to compare the marginal seal of Class II cavities restored with indirect inlays constructed on glass ionomer cement linings having different curing properties. Also the effect of acid-etching of these liners on microleakage was investigated. Mesio-occlusal and disto-occlusal cavities in 80 extracted human molars having the cervical floor below the cementoenamel junction were prepared (n:160). Half of the preparations were restored with Ceramco II porcelain and the rest with SR-Isosit resin inlay material. Liners as light curing Ionoseal light+chemically curing LCL 8 and Zionomer and chemically curing Ketac-Bond glass ionomer cements (GICs) were used. On mesial preparations GICs were acid-etched but were not on distal preparations. All inlays were cemented with Ultrabond composite material. After thermocycling the teeth were placed in a basic fuchsin dye solution for 24 h, then each tooth was sectioned. By using a stereomicroscope the extent of marginal leakage was scored and statistically evaluated. Microleakage was observed beneath all GIC linings and was more extensive between light curing GIC/dentine interface. By acid-etching of GICs the microleakage between GIC/dentine interface was increased significantly. Whether acid-etching was applied or not a significantly increased microleakage was recorded between chemically curing GIC/composite interfaces. Although the marginal microleakage was witnessed in both inlays, it appeared that porcelain inlays provided a better marginal seal, in comparison to SR-Isosit inlays. PMID- 1453259 TI - Physics and the sounds produced by the temporomandibular joints. Part I. AB - In clinical dentistry, the sounds (clicking) and noises (grating) produced by the temporomandibular joints (TMJ) usually signify dysfunction or disease of the mandibular locomotor system. In an attempt to provide guidance to the general practitioner, this article discusses some pertinent parameters defining the physics of airborne and solid-borne vibrations. PMID- 1453260 TI - Maximum jaw opening capacity in adolescents in relation to general joint mobility. AB - Mandibular jaw opening was related with general joint mobility in a non-patient adolescent group. The angular rotation of the mandible at maximum jaw opening was slightly larger in females than in males and significantly larger in hypermobile individuals. No significant relationship between linear measuring of maximal mandibular opening capacity and peripheral joint mobility was found either at active (AROM) or at passive range of mandibular opening (PROM). PROM was strongly correlated to the mandibular length. Clinical signs in the great jaw closer muscles could not be associated to decreased AROM. The mean value of the difference between PROM-AROM (DPA) was 1.2 mm. Frequent clenching and/or grinding was correlated to increased DPA only in hypermobile adolescents (r = 0.49***). Those with DPA exceeding 5mm had all reciprocal clicking. PMID- 1453261 TI - Electromyographic parameters related to clenching level and jaw-jerk reflex in patients with a simple type of myogenous cranio-mandibular disorder. AB - A discriminant analysis has been applied on several electromyographic (EMG) parameters of the masseter and the anterior temporal muscles, related to clenching and the jaw-jerk reflex, to characterize jaw muscle function of patients with craniomandibular disorder (CMD) with respect to controls. The subject samples, matched for age, consisted of 20 females with myogenous CMD, and 20 symptom-free females. The jaw-jerk reflex was elicited by a downward-directed mandibular load, transmitted by a bite-fork causing a similar occlusion and bite rise as a splint. The patients differed mainly from the controls by smaller maximum EMG activity in both muscle groups (P less than 0.05 with the bite-fork inserted). This finding was related to a smaller muscle strength as the EMG level did not improve with pain-free jaw muscles after therapy using a relaxation splint. Discriminating factors of secondary importance were an enhanced bilateral asymmetry in the muscle activity of the patients, and in the reflex amplitude normalized for background EMG activity. In all subject samples, the activity of the anterior temporal muscles decreased with respect to the masseter muscles when the bite-fork was inserted (P less than 0.05-0.001). The therapeutic effect of a relaxation splint may, in part, be related to a relief of the temporal muscles. PMID- 1453262 TI - Shrinkage of tissue conditioners with time--effect of the particle size in powder and the EtOH content in liquid. AB - The dimensional change of tissue conditioners with time was measured until 4 weeks after mixing. Shrinkage of the materials was evaluated in relation to particle size in powder and the EtOH content in liquid. The dissolution of EtOH and plasticizer were also measured to investigate the relation to dimensional change. Shrinkage with time was recorded. The smaller the particle size in powder and the more EtOH in liquid, the greater the shrinkage rate. The smaller the particle size in the powder and the more EtOH contained in the liquid, the greater the dissolution of EtOH. The dissolution of BPBG was below 1/100 comparing that of EtOH and no difference was recognized by particle size and EtOH content. On the basis of these results it is suggested that the dissolution of EtOH is related to shrinkage of tissue conditioners with time and that the component particle size in the powder and EtOH content in the liquid have a significant influence on dissolution of EtOH associated with shrinkage. PMID- 1453263 TI - Relationship between autoregressive model coefficients of EMG and its potentials of jaw closing muscles at rest position and clenching. AB - At rest position and varied clenching levels at intercuspal position, autoregressive (AR) models of myoelectrical activities of both masseter and anterior temporal muscles of 11 healthy subjects with intact natural dentitions were established. The relationship between the AR model coefficients of surface EMGs and their potentials was analyzed by multiple linear regression. It was found that the fourth order coefficient of AR had the greatest effect on the EMG potential levels and their relationship was positive in all recorded muscles. The results indicate the AR coefficients may become a characteristic parameter to describe myoelectrical activity of jaw closing muscles. PMID- 1453264 TI - Effect of mechanical pressure on the blood flow in human palatal mucosa measured by temperature controlled thermoelectrical method. AB - Mucosal blood flow in the human palate was measured by a temperature controlled thermoelectrical method based on the thermal conductivity of mucosal tissue using a blood flow monitor and a non-invasive surface probe. The effect of mechanical pressure on the palatal mucosal tissue was studied. Mechanical pressure (2.5, 5.0, 7.5, 10.0 or 15.0 g mm-2) to the mucosal surface was exerted circumferentially around the surface probe. In five out of seven subjects, the blood flow showed a tendency to be almost constant under the mechanical pressures which are 10.0 g mm-2 or higher. The effect of the duration of the pressure (10.0 g mm-2) exertion on the blood flow was also investigated and it was revealed that the blood flow tended to be constant after 60s in every subject. In the present study, it was also demonstrated that the temperature controlled thermoelectrical method is appropriate for studying the blood flow dynamics in oral mucosa. PMID- 1453265 TI - A new guide for positioning of maxillary posterior denture teeth. AB - There is no definitive method for the arrangement of artificial teeth in complete denture construction. A new method is introduced whereby the maxillary posterior teeth have been set in approximate positions mediolaterally similar to their natural predecessors. The procedure is based on a constant relationship derived from the natural dentition. Its clinical application proved to be suitable for the arrangement of artificial teeth for complete dentures with minimal errors. PMID- 1453266 TI - Observation of proportionality of myoelectrical activity of anterior temporalis to masseter muscle during clenching at varied jaw positions. AB - Twelve healthy subjects with an intact permanent dentition and normal occlusion were selected for sampling of myoelectrical activity of their left and right anterior temporal and masseter muscles during habitual clenching level in varied positions. The proportionality of normalized myoelectrical potentials of anterior temporal muscle to masseter muscle at ICP and RCP was greater than one, while the proportionality at PP was less than one. In the lateral position, the proportionality on the working side was approximately equal to that at RCP, while the proportionality on the non-working side was similar to that at PP. These results suggest that temporal muscle contraction can bring the mandible upward and backward whilst the masseter muscle can elevate the mandible upward and forward. PMID- 1453267 TI - Retinoblastoma and p53 gene expression related to relapse and survival in human breast cancer: an immunohistochemical study. AB - Inactivation of tumour suppressor genes may be an important aetiological factor in many human cancers including breast. In a study of 197 breast cancer patients, tumour tissue was snap-frozen at the time of surgery and immunohistochemical labelling for p53 protein and retinoblastoma (Rb) gene product carried out using an indirect immunohistochemical technique. Tumours were scored by two independent observers for the intensity of nuclear staining for each antibody. Expression of p53 protein showed a significant association with a shorter time to relapse (P = 0.03) and death (P = 0.02) (log rank test). p53 expression did not correlate with nodal status but showed a significant association with high tumour grade (P = 0.001). Rb gene expression showed no relationship to relapse or survival but loss of expression showed a significant correlation with positive lymph node status. The manner by which these proteins might act to determine tumour behaviour remains to be established. PMID- 1453268 TI - Inhibin (10.7 kD prostatic peptide) in normal, hyperplastic, and malignant human endometria: an immunohistochemical study. AB - The expression of inhibin, a 10.7 kD follicle-stimulating hormone (FSH) suppressing prostatic peptide of 94 amino acids, was investigated in normal human endometrium, endometrial hyperplasia, and adenocarcinoma, employing the avidin biotin immunoperoxidase technique. The antiserum used was raised in rabbits against prostatic inhibin isolated from human seminal plasma. The study included 15 well differentiated, 32 moderately differentiated, and 21 poorly differentiated endometrial adenocarcinomas; 26 simple, five complex, and two complex atypical endometrial hyperplasias; and, for comparison, 25 normal proliferative and 30 normal secretory endometria. In malignant and hyperplastic endometrial tissues, inhibin was localized in the epithelial cytoplasm of endometrial glands while the stroma showed weak reactivity. On the other hand, inhibin was undetectable in the early proliferative phase, but was present on the luminal border of the glandular epithelium in the mid- and late proliferative phases. Secretory endometrium displayed strong inhibin reactivity in the cytoplasm of glandular epithelium and in the stroma. The increased inhibin reactivity in secretory endometrium as compared with the proliferative phase is indicative of a functional role for inhibin in the uterus. In addition, its localization in proliferative, hyperplastic, and malignant endometria suggests a possible regulatory role for inhibin in endometrial proliferation and growth. PMID- 1453269 TI - Evaluation of PGP9.5 in the diagnosis of Hirschsprung's disease. AB - The ability of an acetylcholinesterase-stained frozen section to detect an increase in large cholinergic nerve fibres within the muscularis mucosae and extending into the lamina propria was a significant step forward in the diagnosis of Hirschsprung's disease (HD). However, such frozen section diagnosis is not always possible. The purpose of this study was to assess the ability of PGP9.5 to detect this pattern of mucosal nerve fibre staining immunohistochemically. Sixty four specimens were included in the study. Twenty-six of these had been diagnosed as HD by conventional means. All cases were stained immunohistochemically with PGP9.5, S100, and anti-neurofilaments (NF). Twenty-four cases of HD were also stained with neurone-specific enolase (NSE). PGP9.5 reliably stained fibres in the mucosal and submucosal plexuses, and ganglion cells, when the latter were present. This positive staining of ganglion cells was more intense than that seen with NSE, and the positive fibre staining was more intense than that seen with NF. Increased lamina propria fibres were detected with PGP9.5 in only 37 per cent of HD cases compared with S100 positive staining in 60 per cent of cases. However, when S100 staining was assessed alone, it gave a higher false-negative rate in diagnosing HD than PGP9.5 used alone. Therefore we would recommend the use of PGP9.5 and S100 together for the immunohistochemical diagnosis of HD in formalin-fixed biopsies. PMID- 1453270 TI - The peritubular myofibroblasts in the testes from normal men and men with Klinefelter's syndrome. A quantitative, ultrastructural, and immunohistochemical study. AB - The ultrastructure and immunostaining with antibodies against actin, desmin, and vimentin were studied in the peritubular myofibroblasts of testes from normal men and men with Klinefelter' syndrome (KS). The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In control testes, only types a and b tubules were present, whereas the testes from men with KS showed types b, c, d, and e tubules. The ultrastructural study revealed abundant microfilament bundles with electron-dense bodies in the cell periphery of the myofibroblasts in a and b tubules. In c tubules, the microfilament bundles of the myofibroblasts were lacking in electron-dense bodies. Myofibroblasts in tubules d and e showed scanty microfilament bundles. Immunostaining of peritubular myofibroblasts with anti actin antibodies was intense in tubule types a-c and scanty in types d and e. Immunostaining of myofibroblasts with anti-desmin antibodies was intense in tubule types a and b, and negative in types c-e. Immunostaining with anti vimentin antibodies was weak in tubule types a-c and intense in types d and e. Quantitative study revealed that with the progression of sclerosis, the number and volume per cross-sectioned tubule of actin-containing cells and, mainly, desmin-containing cells decrease while the number and volume of vimentin containing cells increase. PMID- 1453271 TI - Immunohistological detection of tumour growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissues. PMID- 1453272 TI - The potential values of fractal dimension measurement in histopathology. PMID- 1453273 TI - Far-UV photochemistry and photosensitization of 2'-deoxycytidylyl-(3'-5') thymidine: isolation and characterization of the main photoproducts. AB - Far-UV irradiation of 2'-deoxycytidylyl-(3'-5')-thymidine (dCpT) gave rise to the pyrimidine (6-4) pyrimidone adduct and its Dewar valence isomer as the main photoproducts. The absolute configuration of the former adduct was determined and its photoisomerization studied. A comparison of the alkali lability of both compounds showed that hydrolysis of the phosphodiester bond occurs for the Dewar valence isomer but not for its (6-4) precursor. In addition, the trans-syn and cis-syn cyclobutane dimers of dCpT were obtained by acetophenone photosensitization and characterized. Finally, the deamination rate constants for this series of compounds were shown to be dramatically influenced by the nature and the configuration of the photoproducts. PMID- 1453274 TI - Laser photolysis of cytosine, cytidine and dCMP in aqueous solution. AB - Laser photolysis of cytosine and cytosine derivatives (cytidine and 2' deoxycytidine-5'-monophosphate) using acetone as a sensitizer have been carried out in aqueous solution using a KrF laser. The absorption spectra of triplet states of cytosine and cytosine derivatives have been observed for the first time. From detailed kinetic analyses, the reaction mechanisms including triplet triplet excitation transfer, and intramolecular excitation transfer within the exciplex arising from the interaction of triplet acetone with cytosine and cytosine derivatives, have been suggested. Accordingly, a series of kinetic parameters have also been obtained. PMID- 1453275 TI - Photoinduction of albino-3 gene expression in Neurospora crassa conidia. AB - The synthesis of carotenoids is induced by blue light in Neurospora crassa mycelia, while in conidia (the vegetative spores) the accumulation of carotenoids also occurs in the dark. The expression of the albino-3 (al-3) gene (coding for the carotenogenic enzyme geranyl-geranyl pyrophosphate synthetase) in isolated conidia was analysed. The level of al-3 mRNA was shown to be increased in light induced wild type (wt) conidia. This light response was elicited by blue light and was under the control of the white collar-1 (wc-1) and white collar-2 (wc-2) gene products. This indicates that the blue-light photoreceptor and the light transduction pathway which activate al-3 gene expression in mycelia are probably the same as in conidia. PMID- 1453277 TI - The Water Pressure Integrity Test--a new integrity test for hydrophobic membrane filters. AB - Sterilizing grade hydrophobic filters are used for the sterile filtration of gases in pharmaceutical and biological applications. Until now the integrity of these membrane filters and their ability to retain bacteria, has been correlated to a solvent based nondestructive integrity test. Current methods use solvents to wet the membranes in order to perform bubble point and diffusion integrity tests. Solvent based integrity tests make it difficult to test in situ following sterilization because of the risk of downstream solvent contamination. A newly developed method, the Water Pressure Integrity Test (WPIT), allows for the integrity testing of hydrophobic filters eliminating the problems associated with traditional test methods employing solvents. A prime advantage of WPIT is that it may be performed in situ post sterilization without any downstream manipulations. The test has been directly correlated to the retention of bacterial challenges. Data will be provided to show the reliability and sensitivity of this easy to perform test. PMID- 1453276 TI - Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs. AB - Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which involves the use of photoactivatable compounds to selectively destroy tumors. 5-Aminolevulinic acid (ALA) is an endogenous substance which is converted to protoporphyrin IX (PpIX) in the synthetic pathway to heme. PpIX is a very effective photosensitizer. The goal of this study was to evaluate the effect of PDT using topical ALA on normal guinea pig (g.p.) skin and g.p. skin in which the stratum corneum was removed by being tape-stripped (TS). Evaluation consisted of gross examination, PpIX fluorescence detection, reflectance spectroscopy, and histology. There was no effect from the application of light or ALA alone. Normal non-TS g.p. skin treated with ALA and light was unaffected unless high light and ALA doses were used. Skin from which the stratum corneum was removed was highly sensitive to treatment with ALA and light: 24 h after treatment, the epidermis showed full thickness necrosis, followed by complete repair within 7 d. Time dependent fluorescence excitation and emission spectra were determined to characterize the chromophore and to demonstrate a build-up of the porphyrin in the skin. These data support the view that PDT with topical ALA is a promising approach for the treatment of epidermal cutaneous disorders. PMID- 1453278 TI - Microbiological validation of a new manufacturing complex for an injectable biological product. AB - The Raritan Biological Production Facility (RBPF) at Ortho Pharmaceutical Corporation, Raritan, NJ, is a unique facility designed and built exclusively for the production of a sterile, injectable biological product of murine monoclonal origin. This product is the first injectable monoclonal antibody product to be licensed by FDA's Center for Biologics-Evaluation and Research (CBER). Thus, Ortho's Biotechnology Division had a unique opportunity to work very closely with CBER throughout all aspects of facility design, construction and validation, including microbiological validation of the facility and its equipment. This paper will address how existing guidelines for pharmaceutical and sterile products were used to develop initial validation protocols for the different areas and applications within the facility, and how the data gathered were used, with the assistance of CBER, to develop operating specifications and monitoring programs, for the operations within the complex. PMID- 1453279 TI - Chemical stability of two sterile, parenteral formulations of cyclophosphamide (Endoxan) after reconstitution and dilution in commonly used infusion fluids. AB - The commercially available parenteral dosage forms of cyclophosphamide (Endoxan, Cycloblastine) are manufactured by an aseptic dry-filling technique and exhibit a slow dissolution rate. A novel dosage form has been developed by one of the manufacturers based on the technique of freeze drying. Dissolution rates of both types of formulations were determined and it was shown that the freeze-dried formulation dissolves more rapidly, within 20 seconds, while it takes at least three minutes to dissolve the dry-filled formulation. The chemical stabilities of the cyclophosphamide solutions, obtained after reconstitution and/or dilution of both formulations, have been investigated and tested as a function of drug concentration (20 and 1 mg/mL), solvent (water, 0.9% sodium chloride, 5% dextrose), container material (glass and polyvinyl chloride (PVC)), light conditions (normal room fluorescent light/dark) and temperature (4 degrees, 20-22 degrees and 37 degrees C). The test solutions were analyzed by a stability indicating reverse phase high performance liquid chromatographic method with ultraviolet detection at 214 nm. Cyclophosphamide solutions (solvent: water; drug concentration; 20 mg/mL) are stable when stored for seven days at 4 degrees C in the dark. At higher temperatures degradation occurred during the test period with 10% loss after seven days at ambient temperature and 50% loss after seven days storage at 37 degrees C. Similar data were found in admixtures with 5% dextrose and 0.9% sodium chloride and initial drug concentration of 1 mg/mL. There are no significant differences in chemical stability between the solutions obtained from reconstitution and dilution of the dry-filled and lyophilized formulations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453280 TI - Temperature profiles and sterilization within a dead-ended tube. AB - Use of steam-in-place (SIP) sterilization has increased as the complexity of biotechnology processing equipment has increased. Extensive biological testing is required prior to use of this equipment as no quantitative guidelines exist for the design of SIP sterilizable equipment. Dead-ended geometries present the most difficult challenge to SIP sterilization, but data are not available as to the effects of tube orientation, length and diameter on time required for sterilization. This study examines the effects on sterilization of location within a dead-ended tube and orientation of the tube with respect to the gravitational vector. Temperature profiles and biological kill of Bacillus stearothermophilus were determined for four tube orientations. Kill kinetics were characterized by time to start of kill and cycle log reduction (CLR) times. Both values increased with increasing distance up the tube and orientation of the tube in a more horizontal position. CLR values were as much as ten times greater than those resulting from saturated steam. Projected sterilization times were determined and found to be very dependent on tube orientation. Recommendations are given for sterilization and validation testing of dead-ended geometries. PMID- 1453281 TI - Formulation development of frozen parenteral dosage forms. AB - Many of the intravenously administered drug compounds are formulated as frozen dosage forms due to lack of sufficient chemical stability at room or refrigerated temperatures. The product is stored in a freezer in the hospital pharmacy and thawed prior to its use. These products therefore, require a long-term frozen shelf-life plus a short-term room temperature and/or refrigerated temperature shelf-life. The formulation is optimized for overall stability in the frozen state as well as in the thawed state. In this paper, the significance of phase changes in the frozen state and the influence of various formulation factors such as drug concentration, diluent, buffer concentration, pH, and raw material purity on the drug stability in the frozen state is reviewed. An overview of analytical and manufacturing considerations unique to frozen products is also presented. PMID- 1453283 TI - Compendial issues: Japan. PMID- 1453282 TI - A comparison of two commercially irradiated Trypticase Soy Agars containing lecithin and polysorbate 80. AB - Gamma-radiation sterilized Trypticase Soy Agar containing lecithin and polysorbate 80 (TSA++) (Becton Dickinson Microbiology Systems, Cockeysville, MD) and irradiated TSA++ (Adams Scientific, West Warwick, RI) were tested by a quantitative spread plate method. Four bacteria Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 10145, Staphylococcus aureus ATCC 25923, Streptococcus pyogenes ATCC 19615 and the yeast Candida albicans ATCC 10231 were tested in two separate experiments using different lots of media. A strain of Aspergillus niger ATCC 16404, was tested by a qualitative streak plate method. The Becton Dickinson Microbiology Systems (BDMS) irradiated TSA++ overall recovered a greater number of organisms than the Adams Scientific TSA++ in both experiments and allowed for the earlier recovery of S. pyogenes ATCC 19615. The growth of A. niger ATCC 16404, was comparable on both media. Efficacy of the media to neutralize 1, 2 and 3% phenol as well as 0.001, 0.01 and 0.1% benzalkonium chloride (BC) solutions was done by a disk diffusion method using 2 gram-positive and 4 gram-negative bacteria. Both media showed complete neutralization of the 0.001 and 0.01% BC solutions and partial neutralization of the 0.1% BC solution. The BDMS TSA++ showed better neutralization of the 2 and 3% phenol solutions than the Adams Scientific TSA++. This data indicates that not all irradiated TSA++ media perform in an equivalent manner. PMID- 1453284 TI - Routine growth monitoring and assessment of growth disorders. AB - Pediatric nurse practitioners have an important role in the routine monitoring of growth and the assessment of growth disorders. The development of good history taking skills and an accurate, repeatable measurement technique are central to the success of growth assessment and evaluation. Numerous causes exist for growth disorders. The pediatric nurse practitioner can be instrumental in identifying these disorders and in making appropriate referral to a pediatric endocrinologist for further evaluation and treatment. PMID- 1453285 TI - Assessment of infant growth. AB - Growth is one of the best indicators of neonatal and infant well being. By comparing the growth of an individual infant over a period of time with available standards, the determination can be made, within limitations, whether the infant is doing as well as should be expected or whether any growth abnormalities exist. The three most common physical measurements of growth are weight, length/height, and head circumference. Normal growth patterns and factors that impact growth within the first 2 years of life are discussed, with recommended techniques for assessment. PMID- 1453286 TI - The impact of genetic syndromes on children's growth. AB - Genetic syndromes that include short stature are recognized by their effect on children's growth rates, by their effect on the growth rate and pubertal development in adolescence, and by the presence of stigmata associated with certain syndromes. The effects of Down, Seckel, Turner, Russell-Silver, Prader Willi, and Noonan syndromes on growth and the growth-inhibiting features of achondroplasia, hypophosphatemic rickets, and Laron dwarfism are reviewed. The terminology used by professionals in discussing genetic alterations should minimize the effects of labeling and stigmatization and should emphasize the normal aspects of a child's life. PMID- 1453287 TI - Accelerated growth in children. AB - Many tall-statured children will display variations of normal growth patterns, such as familial tall stature or familial rapid maturation. However, precocious puberty and a number of rarer diseases that can cause accelerated growth require the earliest possible detection and treatment to ensure that underlying problems are appropriately treated and optimum final adult height is attained. Most of these syndromes are rare. Nevertheless, the pediatric nurse practitioner should be acquainted with them to make timely and appropriate referrals to endocrinologists, geneticists, cardiologists, or orthopedists. PMID- 1453288 TI - Educational, psychologic, and social aspects of short stature. AB - Children with short stature may experience academic difficulties, psychologic impairment, and emotional stress related to an underlying medical condition or social stigmatization. Educational and psychosocial problems associated with short stature often can be alleviated with appropriate interventions. Parents, health-care practitioners, and teachers should be aware of the potential academic, psychologic, and social problems related to short stature and growth delay, so they can support the short child's normal development and intervene promptly if problems arise. PMID- 1453289 TI - Perinatal mortality and morbidity--the Scottish perspective. AB - Although perinatal mortality has continued to fall in Scotland during the last decade, there has been little change during the last three years i.e. 8.9, 8.9, 8.7 per thousand births respectively. Many deaths still result from antepartum haemorrhage and unknown causes so the Scottish Perinatal Mortality group is undertaking a confidential enquiry into the deaths of all normally formed infants of birthweight greater than 2500 g. The other major cause of prenatal death i.e. preterm delivery is also associated with a significant risk of neurological impairment. Results from the Scottish Low Birthweight Study show that 5.7 per cent and 9.5 per cent of very low birthweight infants have severe and moderate disability respectively, reveal once again the importance of research into the primary and secondary prevention of preterm delivery and the care of the preterm neonate. PMID- 1453290 TI - A comparison of postoperative morbidity following prophylactic antibiotic administration by combined irrigation and intravenous route or by intravenous route alone during cesarean section. AB - This study compared the efficacy of a single intravenous dose of Cefazolin alone or combined with an antibiotic containing preclosure-irrigation solution in patients undergoing cesarean section. A total of 308 patients were prospectively assigned to two groups by randomization. Group I received two grams of Cefazolin IV and abdomino-peritoneal irrigation with saline. Group II received one gram of Cefazolin IV and one gram in the saline irrigation solution. The rate of total postoperative morbidity was 2.3 times higher in Group I compared to Group II (16/154 or 10.4% vs 7/154 or 4.5%) and morbidity at the operative site was six times higher (13/154 or 8.4% vs 2/154 or 1.3%). PMID- 1453291 TI - Differences in somatic and organ growth rates in infants who died of sudden infant death syndrome. AB - The aim of present investigation was to study the changes in weight and external measurements and the rates of growth of the internal organs and to compare these findings in infants who died of the sudden infant death syndrome (SIDS). The subjects were 165 infants (100 males and 65 females) who died in Leningrad in 1983-1989 in the first five months of life. Relative growth rates for each month were calculated for weight, external measurements and organ growth, and their ratio was also calculated. Apparent discordance in growth rates was revealed when contrasting the rates for weight, length, head and chest circumference to the growth rates of internal organs and when compared them with each other. The present data show the relation of specific growth patterns to SIDS. PMID- 1453292 TI - In vitro lymphocyte functions in the presence of bovine surfactant and its phospholipid fractions. AB - Endotracheal administration of human or xenogenic surfactant preparations is an effective treatment of the respiratory distress syndrome of preterm infants. The application of large amounts of phospholipids to the lung may result in a significant alteration of the local immune response. We studied the influence of the bovine surfactant preparation SF-RI 1 (Alveofact) on lymphocyte functions in vitro. PHA-induced cell proliferation and immunoglobulin synthesis in the presence of whole surfactant as well as six different defined phospholipids were investigated. A marked concentration-dependent suppression of immunoglobulin production independent of the immunoglobulin isotype and cell proliferation was observed in the range of 5 ng/ml-3 mg/ml of a single phospholipid (or SF-RI 1 respectively). It could be demonstrated that suppression of lymphocyte functions was only due to the phospholipid content of the surfactant preparation. These data indicate that in vivo immune functions may be significantly altered by the administration of exogenous surfactant. This may be particularly important in the presence of primary or secondary pulmonary infections. PMID- 1453293 TI - Calcium dependence of endogenous acetylcholine release into the fetal circulation of the dually perfused human placental lobule. AB - The aim of this study was to examine the role of calcium in the release of acetylcholine (ACh) from the fetal circulation of the dually perfused human placenta. The viability of this preparation was demonstrated; Glucose consumption and lactate production (as sums of both the fetal and maternal values) over the 4 h perfusion period were 13.9 +/- 4.2 mmol/kg/h (mean +/- SEM, n = 7) and 15.1 +/- 2.0 mmol/kg/h (n = 13) respectively. Mean pH levels of the fetal and maternal effluent perfusates were 7.26 +/- 0.02 (n = 5) and 7.32 +/- 0.01 (n = 5). None of these parameters varied significantly from 1 to 4 h of perfusion. ACh output into the fetal vessels after 1 h of perfusion was 0.31 +/- 0.02 nnmol/min/g wt weight (n = 5) in the presence of physostigmine (2.7 uM) and did not vary significantly from 1 to 4 h of perfusion. Perfusion with Ca+(+)-free Krebs solution and 2 mM EDTA (but not with Krebs in the absence of EDTA, or with both Ca++ and EDTA, or in the presence of 3.78 mM Ca++) for 60 min resulted in a significant reduction of ACh output in the fetal perfusate. Output in the former case was partially restored on subsequent perfusion with normal Krebs for 60 min. These results suggest ACh release in perfused human placenta lobules is at least partially Ca+(+)-dependent. PMID- 1453294 TI - Determination of t-PA activity and t-PA antigen in human milk. AB - Although a considerable number of publications on tissue plasminogen activator (t PA) in human milk have appeared, most investigators have determined t-PA activity using an assay on fibrin plates [1, 2, 3, 4]. We measured t-PA activity by a bioimmunoassay and t-PA antigen by ELISA using a monoclonal antibody (SP-322) [6], and estimated t-PA index ((t-PA activity, ng/ml)/(t-PA antigen, ng/ml) x 100) in human colostrum and milk to evaluate the fluctuations of post-delivery t PA. The concentrations of t-PA activity decreased slowly related to the duration of lactation varying between days one and two hundred and ten and showed significant negative correlation with the duration (P less than 0.001). The t-PA antigen made a slow descent, followed by a reciprocal ascent of the t-PA index to the fifty eighth post-delivery day and showed significant correlations with the duration (P less than 0.001, P less than 0.05, respectively). This information suggests that a high concentration of t-PA may be released into the narrow channels of the glands functioning to maintain duct patency under the regulation of an inhibitor such as plasminogen activator inhibitor (PAI). PMID- 1453295 TI - Fetal breathing movements and prostaglandin levels in pregnancies complicated by premature rupture of the membranes. AB - We have previously demonstrated that maternal and fetal prostaglandin levels may be elevated in patients with pregnancies complicated by premature and prolonged rupture of the membranes (PPROM) compared to patients with intact membranes. In the fetal lamb, infusion of prostaglandin abolishes fetal breathing movements and in human pregnancies with PPROM and with poor outcome, fetal breathing movements are absent. The aim of this study was to determine fetal breathing activity in pregnancies complicated by PPROM which had elevated prostaglandin levels. One hour ultrasound examinations were performed on nine fetuses whose mothers had had premature rupture of the membranes at 28 weeks gestation and a median of 4 days prior to the ultrasound examination. The number of fetal breathing movements (FBM) and percentage of time that each fetus spent breathing was documented and this was then related to control values. Following the completion of the ultrasound examination, cordocentesis was performed and blood sent for estimation of bicyclo PGEM levels. All of the fetuses made some breathing activity during the one-hour period, but the number of FBM varied from 1 to 181 (median 21). The percentage time that the fetuses spent breathing was much lower than that which would be expected for their gestational age, being a median of 1.3% (range less than 0.1 to 50.8%) of control values. As bicyclo PGEM levels were elevated in these nine fetuses, these data suggest that reduction in breathing activity in fetuses of pregnancies complicated by PPROM may be due to elevated prostaglandin levels. PMID- 1453296 TI - Femoral artery blood flow monitoring has distinct advantages for examining redistribution of blood flow in fetal acidosis. AB - Changes of blood flow in umbilical artery, carotid artery and femoral artery were examined during the progression of acidemia in fetal sheep by means of indwelling transit-time ultrasonic blood flow meters. Moreover, catecholamines in fetal blood were measured and its interrelation to the alteration in blood flow was examined. Gradually progressing fetal acidemia was induced by repeated cord compression. Umbilical blood flow showed a initial increase thereafter maintaining a plateau through the experiment, which seemed to be dependent on fetal arterial pressure. Carotid artery flow gradually increased until the arterial pH in fetal blood declined to 7.20 and remained at this level even though the acidemia further progressed. Femoral artery flow markedly decreased around fetal arterial blood pH 7.20 and its change correlated well with the plasma level of catecholamines. This change of femoral artery flow may be evaluated by examination of the flow index as well as flow volume. Redistribution of blood flow in the progression of fetal acidemia may be initiated at around fetal arterial pH 7.20 and can be detected by studying femoral artery flow. PMID- 1453297 TI - Catecholamine abnormalities in transient tachypnoea of the premature newborn. AB - The aim of the present study was to assess if there was an association between low catecholamine levels at birth in the premature infant and the development of TTN. Blood samples were collected at delivery from the umbilical artery of all preterm infants with a gestational age less than 36 weeks for determination of pH and catecholamine levels (noradrenaline and adrenaline). Amongst non-asphyxiated infants only, cord pH greater than 7.25 and/or Apgar score greater than 7 at five minutes, catecholamine levels were compared between the 10 infants who developed transient tachypnoea of the newborn (TTN) and 13 controls of a similar gestational age range (31-35 weeks) who developed no respiratory distress in the neonatal period. Infants who developed TTN were more often delivered without labour, 8 of 10 compared to 2 of 13 controls (p less than 0.01). There were no significant differences in adrenaline levels between the two groups. Noradrenaline levels, however, were significantly lower in the infants who developed TTN, being a median of 3.1 nmol/l (range 1.07-5.85 nmol/l) compared to a median of 6.4 nmol/l (range 2.38-22.83) in the controls (p less than 0.01). Infants who were delivered following labour had significantly elevated noradrenaline levels compared those delivered without labour (elective delivery) (p less than 0.05). These results suggest that low noradrenaline levels in preterm infants may explain the association in this group of TTN and "elective" delivery. PMID- 1453298 TI - The prediction of fetal compromise and acidosis by biophysical profile scoring in the small for gestational age fetus. AB - In a prospective blind study, 133 fetuses suspected of being small for gestational age (SGA), defined as an estimated fetal weight less than the 10th centile for gestation, were monitored by weekly biophysical profile assessment. Perinatal outcome was assessed by umbilical venous blood pH estimation and compared with the profile score determined within seven days of delivery. The positive and negative predictive values of the full biophysical profile score were not significantly better than combinations of two or three of the individual components in this group of fetuses. The use of amniotic fluid volume, non-stress testing and either fetal movement or breathing offers an acceptable alternative to full biophysical profile assessment in the fetus suspected of being small for gestation. PMID- 1453299 TI - Human choriogonadotropin (hCG) and placental lactogen (hPL) inhibit interleukin-2 (IL-2) and increase interleukin-1 beta (IL-1 beta), -6 (IL-6) and tumor necrosis factor (TNF-alpha) expression in monocyte cell cultures. AB - The effect of the human trophoblast hormones chorionic gonadotropin (hCG) and placental lactogen (hPL) on the expression of cytokines in peripheral blood mononuclear cell cultures was followed under a variety of culture conditions, (a) phytohemagglutinin stimulated cells (PHA-MSC), (b) allogenic mixed cells (AMC) and (c) spontaneously proliferating cells (SPC). A dose dependent enhanced release of IL-6, IL-1 beta and TNF-alpha by hCG and hPL was observed under all culture conditions. However, an inhibitory effect on the IL-2 release was seen in PHA-MSC by hPL and in AMC by hPL and hCG. The role of the suppression of IL-2 production/release on cytotoxicity towards trophoblast is discussed. These results suggest a sensitive, dose dependent hormonal control of the modulation of the immune response during pregnancy and strengthen the concept of a distinct regulation of monocytes and lymphocyte subpopulation by trophoblast hormones. PMID- 1453300 TI - Discordant anencephaly with a cleft lip and palate in a pergonal-induced triplet pregnancy. AB - Anencephaly in triplets and pergonal induced pregnancies is a very rare incident. Associated cleft lip and palate has never been reported in these case. In this paper we report the first case of an anencephalic infant with cleft lip and palate in a set of pergonal-induced discordant triplet pregnancy. PMID- 1453301 TI - Dental implants: a review. AB - The present article is a review presenting an update on the field of dental implants since the World Workshop in Clinical Periodontics in July 1989. Areas that are discussed include following: 1. Biomaterials and the implant interface, and the interaction of these with the environment. 2. Periodontal considerations including data supporting a perimucosal seal of implant to soft tissue and discussion of the endosseous interface between the bone and the implant. 3. Newer techniques of diagnostic imaging and their determination of bone types are related to the future practice of dental implants. 4. Implant selection and the surgical techniques involved in implant placement. 5. Current ideas of implant prosthodontics, implant maintenance, and the treatment of implant failures. 6. Finally, the use of dental implants in the United States and Sweden. PMID- 1453302 TI - The effect of certain systemic medications on oral calculus formation. AB - A quantitative comparison was made of supragingival calculus that formed in individuals using systemic medications for defined systemic medical problems and individuals not using medication. Measurements of supragingival plaque and calculus were made on the lingual surfaces of the 4 mandibular incisors of 68 consecutive patients presenting for dental examinations and oral prophylaxes. Variables noted in addition to medication and plaque status were: age, sex, time interval since previous prophylaxis, and smoking status. Analysis of results indicated a statistically significant reduction of calculus among individuals medicated with beta-blockers, diuretics, anticholinergics, synthroid and allopurinol despite the high quantity of plaque present. PMID- 1453303 TI - Healing of the intrabony periodontal lesion following root conditioning with citric acid and wound closure including an expanded PTFE membrane. AB - The effect of citric acid conditioning of the root surface in conjunction with gingival flap surgery including barrier membranes (expanded polytetrafluoroethylene) was clinically evaluated in 26 intrabony periodontal defects in 23 patients. Control treatment included gingival flap surgery with barrier membranes alone. Twelve defects were treated with the experimental and 14 with the control protocol. Healing was evaluated 12 months after surgery. Initial probing depths approximated 6.9 mm and defect depths measured during surgery exceeded 4 mm. The patients exhibited good oral hygiene over the study interval as substantiated by low plaque and bleeding scores. Acid conditioning of the root surface did not enhance periodontal healing in this study, similar amounts of defect resolution were observed following either treatment protocol. Probing depth reduction generally approximated 1.8 mm; gain of clinical attachment, 0.8 mm; and defect bone fill, 1.2 mm. Under the prevailing conditions, the barrier membrane procedure apparently gave a healing result beyond which further improvement could not be achieved by root surface conditioning. PMID- 1453304 TI - In vitro effects of citric acid application techniques on dentin surfaces. AB - The present study evaluated the in vitro effects of different application techniques of citric acid on dentin root surfaces. Ten freshly extracted, periodontally involved teeth were obtained and 4 dentin slabs, approximately 4 x 6 x 2 mm, were obtained from the roots of each tooth, for a total of 40 slabs. These slabs were identified by tooth and preserved in 1:1 anhydrous glycerol/absolute alcohol solution. Citric acid pH 1 was applied to 32 of the slabs for 5 minutes with one of 4 different techniques: 1) immersion; 2) placed with a saturated cotton pellet with no rubbing; 3) placed and burnished with a saturated cotton pellet; or 4) applied with a camel hair brush. The remaining 8 dentin slabs were used as negative control specimens, root-planed and non-acid treated. Following the various treatments, the slabs were fixed, dehydrated, critical point dried, and coated for scanning electron microscopic (SEM) evaluation. Scanning photomicrographs were obtained at 2,000, 6,000, and 40,000 magnifications. The surface characteristics of the treated dentin slabs were evaluated descriptively regarding the degree of fiber exposure; the number of exposed tubules and the surface area occupied by tubule orifices were also measured. Friedman's 2-way analysis for block designs was employed. Results demonstrated that root-planed, non-acid treated specimens had an amorphous, irregular surface which corresponded to a smear layer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453305 TI - Endotoxin levels in periodontally healthy and diseased sites: correlation with levels of gram-negative bacteria. AB - This study investigated the correlation between endotoxin levels and the percentage of Gram-negative bacteria in healthy sites and in periodontitis sites. Twelve healthy adults participated. Each subject provided 3 periodontitis sites with 5 to 8 mm probing depths that bled on gentle probing and 3 healthy sites with sulcus depths of 1 to 3 mm that did not bleed. Clinical examinations and sterile paper point sampling of all study sites were conducted on days 0, 7, and 14, and site-specific endotoxin levels and percentage of Gram-negative bacteria were determined. There were significant differences in both endotoxin levels and percentage Gram-negative bacteria between healthy and periodontitis sites across all 3 sampling periods, but no difference across sampling periods in the healthy sites and the periodontitis sites, respectively. Correlation coefficients revealed a high degree of correlation between site-specific endotoxin levels and percentage of Gram-negative organisms. Using a sample dilution of 1 x 10(4), endotoxin levels differentiated healthy from periodontitis sites with a specificity of approximately 91% and a sensitivity of approximately 90%. PMID- 1453306 TI - Comparison of presurgical and immediate postsurgical ibuprofen on postoperative periodontal pain. AB - Previous studies have indicated that non-steroidal anti-inflammatory drugs administered prior to oral surgery procedures are effective in reducing postoperative pain. The purpose of the present study was to compare the efficacy of medicating with ibuprofen immediately presurgically to medicating immediately postsurgically on postoperative pain associated with periodontal surgery. Sixty patients who were to undergo periodontal surgery were randomly divided into 3 groups: the I-pretreatment group received 600 mg ibuprofen immediately presurgically and placebo immediately after the surgery; the I-post-treatment group received placebo before surgery and 600 mg ibuprofen postsurgically; the placebo group received placebo at both time periods. Responses from an 8-hour pain diary completed by each subject were quantified and statistically evaluated non-parametrically. Results indicated that dosing with ibuprofen either immediately before or immediately after periodontal surgery significantly delays onset of pain as compared to placebo, with dosing after surgery demonstrating a significantly greater delay of onset of pain as compared to dosing presurgically. In addition, unlike the presurgical dosing, dosing postsurgically significantly decreases mean pain intensity for a combined 8-hour period following periodontal surgery as compared to placebo. PMID- 1453307 TI - Guided tissue regeneration versus mucogingival surgery in the treatment of human buccal gingival recession. AB - A surgical technique involving membranes was used to treat localized human buccal recessions 3 mm to 8 mm. The results on 25 patients (test group) were evaluated 18 months postoperatively and compared with the results obtained in 25 other patients (control group) having undergone mucogingival surgery. In the test group, a trapezoidal flap with a large base was raised beyond the mucogingival junction. The exposed root surface was scaled thoroughly to a concave shape. A membrane was bent and adapted onto the concave root surface. The flap was sutured far coronally and the membrane removed one month later. The control patients underwent a 2-step procedure, consisting of a free gingival graft and a coronally positioned flap. The amount of root coverage obtained was similar in the 2 groups (test = 72.73%; control = 70.87%), although the clinical attachment gain (test = 5.12 mm; control = 3.56 mm) and pocket variation (test = 1 mm reduction; control = 0.06 mm increase) differed significantly (P < 0.001). The keratinized tissue width was greater in the control group. The regression analysis showed that the amount of covered root surface after treatment was in strict correlation with the depth of the original recession in the test group, while no correlation was found in the control group. The expected root coverage was greater in the test group when the recession was greater than 4.98 mm, while it was greater in the control group when the recession was less than 4.98 mm. These results indicate that a guided tissue regeneration procedure can be used to successfully treat recession. The membrane procedure compared favorably with the mucogingival surgery in the treatment of deep recession. PMID- 1453308 TI - A comparison of ePTFE membranes alone or in combination with platelet-derived growth factors and insulin-like growth factor-I or demineralized freeze-dried bone in promoting bone formation around immediate extraction socket implants. AB - The purpose of this study was to compare bone promotion around implants which were augmented with ePTFE membranes alone or in combination with cortical demineralized freeze-dried bone (DFDB) or the combination of platelet derived growth factor-BB (PDGF) and insulin like growth factor I (PDGF/IGF-I). Membranes were placed over titanium implants which had been inserted into fresh extraction sockets with large buccal dehiscences. Twenty-four implants were placed in 4 dogs. At 18 weeks clinical bone height measurements were taken, the animals were sacrificed, and all specimens retrieved for histologic evaluation. Clinically, a significant gain in bone levels was present in both the ePTFE membrane alone group (P < 0.005) and PTFE plus PDGF/IGF-I group (P < 0.01), but not in the PTFE plus DFDB group. Results from histometric measurements revealed an approximately 2-fold increase in the percentage of implant surface in contact with bone, area of bone adjacent to the implant surface, and in the total length of the implant surface in contact with bone in the dehiscence defects treated with ePTFE plus PDGF/IGF-I compared to the defects receiving ePTFE membranes alone (each P < 0.05). The response to the DFDB was highly variable and it did not significantly improve the efficacy of the PTFE membranes for any parameter measured. The distance from the outer surface of the new bone to the implant surface was statistically significant for ePTFE membranes alone and membranes plus PDGF/IGF I. The results demonstrated that clinically, ePTFE membranes alone or ePTFE membranes with PDGF/IGF-I were equally effective in promoting bone growth around the implants. Histologic measurements demonstrated that sites treated with ePTFE membranes plus PDGF/IGF-I had the highest bone density compared with sites which received ePTFE membranes alone or with ePTFE membranes and DFDB. The results of this study question the use of DFDB and support the use of ePTFE membranes alone or with PDG-F-BB/IGF-I as potential methods of promoting bone formation around dental implants. PMID- 1453309 TI - Effects of melatonin on water metabolism and renal function in male Syrian hamsters (Mesocricetus auratus). AB - The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 micrograms of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects. PMID- 1453310 TI - Androgenic function in adult rats: influence of the pineal gland of the mother and of the offspring. AB - Female rats exposed to long (LD 18:6) or short (LD 6:18) photoperiods from 21 days of age were mated when they reached 55 days of age. On day 2 of gestation animals of each group were either pinealectomized or sham-operated. Lighting regimens were not changed during the course of the study. Male offspring of the four groups of dams were sacrificed on day 70 after birth. Rats that were maintained on long photoperiod had higher testicular testosterone, androstenedione, and dihydrotestosterone content than those raised on a LD 6:18 cycle. Whatever the breeding photoperiod used, maternal pinealectomy induced no modification of reproductive function. Among rats kept in short photoperiod, neonatal pinealectomy (on day 5 after birth) resulted in an enhanced testicular androgen content without any modification of plasma androgen concentration. These results indicate that (1) the previously reported effect of the mother's pineal on pubertal rat testicular function is not present in adulthood and (2) the pineal of the offspring is required to maintain normal testicular androgen content in the adult rat but exerts no influence on circulating androgens. PMID- 1453311 TI - Inhibin-like "antigonadotropic" activity in the ovine pineal. AB - In an attempt to define the antigonadotropic activity associated with the protein/peptide extracts of ovine pineals, melatonin- and steroid-free fractions obtained after subjecting crude ovine pineal acetone powder to soft gel chromatography were tested in three bioassay systems: (1) the conventional compensatory ovarian hypertrophy inhibition assay in rats, (2) the coupled bioassay in immature mice that enables one to distinguish factors acting at the level of the pituitary from those acting at the gonadal level, and (3) the classical in vitro pituitary cell culture assay for inhibin. The large molecular weight fraction, referred to as PI, behaved like a classical antigonadotropin as it suppressed compensatory ovarian hypertrophy following unilateral ovariectomy. Further, it not only lowered the basal and gonadotropin releasing hormone (GnRH) stimulated release of follicle stimulating hormone (FSH) by the cultured pituitary cells, but also inhibited the human chorionic gonadotropin (hCG) induced uterine weight gain in the coupled assay, thus acting like inhibin in these two assay systems. In addition, it showed immunological cross-reactivity with ovine testicular inhibin. The present results strongly support the view that inhibin-like activity may be the major player in what has so far been referred to as antigonadotropic activity. PMID- 1453312 TI - Determination of kinetic properties of serotonin-N-acetyltransferase in bovine pineal gland using HPLC with fluorimetric detection. AB - The determination of serotonin-N-acetyltransferase (NAT) activity in the bovine pineal gland and other rat tissues was based upon the separation and detection of N-acetyltryptamine formed from tryptamine and acetyl CoA by means of high performance liquid chromatography with fluorimetric detection. In the bovine pineal the enzyme exhibited a Km value of 31.45 +/- 4.98 microM and a Vmax value of 30.90 +/- 1.18 pmol N-acetyltryptamine/min/mg protein for tryptamine, and a Km value of 28.72 +/- 7.50 microM and a Vmax value of 25.90 +/- 1.50 pmol N acetyltryptamine/min/mg protein for acetyl CoA. The present method is simple, allows the determination of NAT activity from a variety of enzyme sources, has application to pharmacological studies of NAT regulation in tissue cultures, and provides an alternative to current radioenzymatic assays. PMID- 1453313 TI - Effect of immunization against melatonin on seasonal fleece growth in feral goats. AB - Four vaccination protocols were utilized to investigate the effects of immunoneutralizing circulating melatonin on the annual cashmere growth cycle and cashmere production in Australian feral goats. A fluctuating anti-melatonin antibody response, achieved by repeated booster vaccinations, resulted in an acceleration of the growth cycle in goats which exhibited a significant immune response, compared to sham-immunized controls. Responding goats showed two cycles of cashmere length growth in the first 16 months and increased annual cashmere production in the first year. However, in the second year, these effects were no longer apparent, suggesting either some form of desensitization to melatonin, or a diminished response due to declining antibody titre. The effects of immunization were observed in both sexes; the effect on cashmere length was greater in wethers than in does. Cashmere fibre growth in response to a continuously declining plane of specific antibody showed increased cycle frequency, albeit with a decreased amplitude; guard hair growth cycles were affected to a much lesser extent. Small transient peaks of specific immunity at the summer or winter solstice were without significant effect on cashmere growth. Immunization to provoke a persistent anti-melatonin antibody response at the winter solstice resulted in significantly increased greasy fleece weight, % cashmere yield, and mass of cashmere produced, but no change in fibre diameter in both sexes. Thus the timing of cashmere growth cycles in goats may be, at least transiently, altered by appropriately timed immunization against melatonin. The mechanism of pineal-mediated regulation of cashmere growth cycles may involve (i) entrainment of an endogenous rhythm by melatonin, or (ii) seasonal alteration of cashmere follicle sensitivity to the effect of melatonin. PMID- 1453314 TI - Effects of selective histamine receptor antagonists on skin responses to intradermal bradykinin in healthy volunteers. AB - The effects of chlorpheniramine and cimetidine on the cutaneous responses to intradermal injections of bradykinin were investigated in a randomized, double blind, placebo-controlled, cross-over study. Chlorpheniramine significantly attenuated the increase in cutaneous blood flow and erythema induced by bradykinin but not the weal response. Cimetidine was without influence on these parameters and the effects of the combined therapy of chlorpheniramine and cimetidine were not significantly different from those due to chlorpheniramine alone. These results suggest that the cutaneous vasodilator effect of bradykinin is in part due to histamine release acting on histamine H1-receptors. PMID- 1453315 TI - Characterization of human immunodeficiency virus-1-infected cells of myeloid monocytic lineage (ML-1, HL-60, THP-1, U-937). AB - The myeloid-monocytic cells ML-1, HL-60, THP-1, and U-937 were chronically infected (for > 2 years) with the lymphotropic human immunodeficiency virus type 1 (HIV-1) strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1/HIV-1 and HL-60/HIV-1 cells showed a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-1/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers revealed a differential expression of CD4, CD8, CD11c, CD14, CD15, CD20, HLA-DR, and HLA-DQ in non- or chronically infected cells. In chronically infected cells, the steady-state levels for tumor necrosis factor-alpha, interleukin (IL)-1 beta, and granulocyte-macrophage colony-stimulating factor mRNA remained unchanged whereas the one for IL-6 dropped. PMID- 1453316 TI - Pharmacokinetics of dideoxyinosine in pigtailed macaques (Macaca nemestrina) after intravenous and subcutaneous administration. AB - Four macaques (Macaca nemestrina; 1 female and 3 males) were administered dideoxyinosine (DDI) at three dose levels (3.2 mg/kg i.v., 10 mg/kg i.v., and 20 mg/kg s.c.). Blood and urine samples were collected during 6-8 h and 24 h after drug administration, respectively. The mean plasma clearance (16.7 +/- 4.9 ml/min/kg), steady-state volume of distribution (1.5 +/- 0.4 L/kg), and terminal plasma half-life (96.8 +/- 7.5 min) did not differ significantly between the two i.v. doses. DDI was eliminated from the body primarily by excretion of the unchanged drug in the urine (74%). The absorption of DDI from the subcutaneous site was complete (bioavailability of 0.91 +/- 0.13) and rapid, with peak plasma concentration obtained at 30 min. PMID- 1453317 TI - Report of a Consensus Workshop, Siena, Italy, January 17-18, 1992. Maternal factors involved in mother-to-child transmission of HIV-1. AB - Although most children with AIDS have acquired HIV from their mothers, transmission from an HIV-infected mother to her infant is neither uniform nor currently predictable. With the rapid worldwide spread of HIV infection, particularly into women of child-bearing age, definition of the risk factors associated with maternal transmission is essential to develop and deliver intervention therapy that might impact on the devastating spread of AIDS. To promote research defining the risk factors of HIV transmission from mother to infant, an international workshop was held on January 17-18, 1992, in Siena, Italy. Epidemiology, immunology, virology, and health issues associated with maternal HIV transmission were actively discussed by participants. Current information from the literature and new data available from laboratories formed the basis for the consensus opinions developed at the meeting. Wide differences (10-39%) in HIV transmission seen at different geographic sites may be explained by multiple risk factors. The timing of transmission of HIV from mother to fetal, newborn, or breast-fed infants may be further complicated by viral burden and other cofactors. There are intriguing suggestions that the immunological status of the mother may be influential in preventing or reducing HIV transmission. But this appears to be interrelated with the HIV viral burden and health status of the mother and in turn her likelihood to transmit HIV to her offspring. The infecting "inoculum" may be low and/or selective because of biological barriers that favor reduced transmission with good health of the mother and the absence of other infectious diseases. PMID- 1453318 TI - Progressive multifocal leukoencephalopathy in patients with HIV infection: lack of impact of early diagnosis by stereotactic brain biopsy. AB - Thirteen patients with HIV-related progressive multifocal leukoencephalopathy (PML), representing an institutional incidence of 4.2%, are reported. All cases were diagnosed by image guided stereotactic brain biopsy shortly after their presentation for neurologic complaints. All patients were males; risk factors included homosexual or bisexual activity or intravenous drug use. At the time of presentation with PML, the mean T4 count was 85 (range 9-240 cells/mm3). The most common neurologic symptoms were cognitive dysfunction and aphasia, whereas gait abnormalities and disordered cognition were the most common neurologic signs. Cerebrospinal fluid analysis was helpful only to rule out other causes of CNS disease. Magnetic resonance imaging, more sensitive than computed tomography (CT) scanning, typically revealed multiple areas of increased intensity on T2 weighted images although unifocal disease was seen in 23% of patients. Despite early stereotactic biopsy and aggressive symptomatic therapy, survival of these patients was poor with a mean of 2.6 months after the onset of neurological symptoms and 2.0 months after biopsy. PMID- 1453319 TI - The identification and tracking of Candida albicans isolates from oral lesions in HIV-seropositive individuals. AB - Restriction fragment polymorphism analysis was used to investigate the identity and genotypic relatedness of Candida albicans strains isolated from human immunodeficiency virus (HIV)-infected patients with or without oral candidiasis and from some of their sexual partners. Use of the species-specific DNA probe Ca3 revealed that most subjects carried a single distinct C. albicans strain throughout the course of the study, during both symptomatic and asymptomatic periods. Sexual partners were more likely to carry the same or similar C. albicans isolates than unrelated subjects, raising the possibility of transmission via intimate contact. One patient appeared to acquire his partner's isolate, which then became predominant in both partners in subsequent isolations. These findings indicate that recurrent oral candidiasis is usually caused by a single persistent strain unique to each patient, but that in some cases transmission via intimate contact may occur between sexual partners. PMID- 1453320 TI - D-xylose malabsorption: characteristic finding in patients with the AIDS wasting syndrome and chronic diarrhea. AB - The AIDS wasting syndrome (AWS) is characterized by > 10% loss of baseline body weight during 6 months and may occur in patients with or without associated chronic diarrhea. To determine whether the presence of small-intestinal malabsorption is associated with the development of AWS in human immunodeficiency virus (HIV)-infected patients with chronic diarrhea, we retrospectively reviewed the results of D-xylose testing performed in the clinical evaluation of 21 consecutive HIV-infected patients with chronic diarrhea. A thorough search for small-intestinal pathogens was performed including upper endoscopy, duodenal biopsy, and aspirate for culture and ova and parasite examination. These studies were negative in all patients except two who were excluded from the study. In the 19 patients with no identifiable pathogens, the 1-h serum D-xylose concentration was significantly lower in patients with AWS than in those without, 8.3 +/- 0.8 versus 23.7 +/- 3.4 mg/dl, respectively, p < 0.001. Urine D-xylose excretion during 5 h was also significantly lower in the group with AWS, although creatinine clearance was similar in the two groups. Patients with AWS were more often refractory to standard antidiarrheal therapy with loperamide or diphenoxylate and carried a poor prognosis (90% mortality at 1 year versus 22% mortality in the group without AWS). These data indicate that small intestinal malabsorption is a major component in the severe wasting seen in some HIV infected patients with chronic diarrhea. Patients with markedly abnormal D-xylose tests may require more potent antidiarrheal therapy and are expected to have a high mortality as a possible consequence of intestinal dysfunction. PMID- 1453321 TI - Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy, and outcome. AB - To further characterize the clinical features, response to therapy, and outcome of Pneumocystis carinii choroiditis in patients with AIDS, we retrospectively reviewed the course of choroiditis for eight patients identified from two institutions through April 1991. Seven patients had prior Pneumocystis carinii pneumonia and had received aerosolized pentamidine prophylaxis for a median of 10 months; one patient had no prior history of pneumonia or prophylaxis. The median CD4+ lymphocyte count for six patients was 11 cells/mm3. Choroiditis was a preterminal diagnosis for three patients--two with associated disseminated pneumocystosis. Ocular manifestations improved or resolved with therapy for five of the six treated patients. All five subsequently received prophylaxis with dapsone (n = 2), dapsone/trimethoprim (n = 2), or aerosolized pentamidine (n = 1). Choroiditis recurred at 15 months in the one patient receiving aerosolized pentamidine. The median survival from time of diagnosis was 44 weeks. A literature review including an additional 40 cases support the conclusions that (a) Pneumocystis choroiditis is a rare complication of advanced HIV disease, occurring often in the context of systemic pneumocystosis; (b) ocular signs and symptoms may improve or resolve with specific antipneumocystis therapy; and (c) relapse may occur, particularly in those not receiving systemic prophylaxis. PMID- 1453322 TI - Rhodococcus equi cavitary pneumonia in HIV-infected patients: an unsuspected opportunistic pathogen. AB - Two patients seropositive for human immunodeficiency virus (HIV) and with no previous acquired immunodeficiency syndrome-defining conditions developed cavitary pneumonia and pleural disease caused by Rhodococcus equi. R. equi was isolated from these patients' sputum and lung biopsy specimens, respectively, but the microorganism was initially considered to be a contaminant (patient 1) or misidentified as a nontuberculous mycobacterium (patient 2). The R. equi infection was fatal in one patient, who died after 4 months without specific antimicrobial therapy; the second patient was unresponsive to combination therapy with various antimicrobial agents. R. equi may cause life-threatening infections in HIV-infected patients. Microbiology laboratories should be cognizant of the need to exclude R. equi as a cause of infection in highly immunosuppressed patients. PMID- 1453323 TI - The effect of antiviral therapy on the natural history of HIV infection. PMID- 1453324 TI - Very low seroprevalence of HTLV-I in patients with gynecologic disorders in Thailand. PMID- 1453325 TI - HIV disease and AIDS in women: current knowledge and a research agenda. AB - The study of the clinical manifestations, progression, and outcome of human immunodeficiency virus (HIV) infection in women has begun in earnest. AIDS defining diseases that are more common in women than in men include wasting syndrome, esophageal candidiasis, and herpes simplex virus disease, whereas Kaposi's sarcoma is rare. Non-AIDS-defining gynecological conditions such as vaginal candida infections and cervical pathology are prevalent among women at all stages of HIV infection. Associations have been documented between the presence of human papillomavirus, lower genital tract neoplasia, and HIV-related immunosuppression. Pregnancy has not been confirmed to have an effect on the clinical progression of HIV disease in women incremental to the effect of time. Differential access and utilization of therapeutic interventions appear to account for much of the reported gender discrepancy in survival. Well designed epidemiological and clinical studies will help further scientific knowledge leading to early diagnosis, appropriate treatment, and timely prevention of the manifestations of HIV disease in women. PMID- 1453326 TI - HIV-1 and HIV-2 infections in a high-risk population in Bombay, India: evidence for the spread of HIV-2 and presence of a divergent HIV-1 subtype. AB - A high-risk population (patients of a sexually transmitted disease clinic and the GT hospital in Bombay) was tested for antibodies against HIV-1 and HIV-2. Among 405 serum samples, 226 had previously been classified HIV-positive in India using different locally available enzyme-linked immunosorbent assay (ELISA) tests. The serology of 179 samples was unknown. All 405 samples were tested at the Georg Speyer-Haus (GSH) with the Pasteur HIV-1/2-Combi-ELISA. Positive samples were further analyzed with HIV-1 and HIV-2 Western blot kits from Dupont and Pasteur, respectively. A very high seroprevalence of HIV was found in this population. Among the 179 unscreened samples, 69 (38.5%) were positive in the ELISAs as well as the Western blots for HIV-1 or HIV-2. Among the prescreened samples, only 174 (77%) were confirmed HIV-positive. Altogether, 243 of 405 sera were HIV-positive. Of these, 184 (76%) were reactive with HIV-1, 10 (4%) were reactive with HIV-2, and 49 (20%) had dual reactivity to HIV-1 and HIV-2. Previous data from the Indian Council of Medical Research had already suggested a possible high prevalence of HIV-1 in India. Our results confirm this view. The finding of a substantial spread of HIV-2 infection was, however, totally unexpected in India, but confirms our previous study which had already demonstrated the existence of HIV-2 in this country. Asia can thus no longer be considered free of HIV-2, and testing for HIV-2 appears mandatory, at least in India.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453327 TI - Variations in inpatient mortality for AIDS in a national sample of hospitals. AB - In this project, we examined the spectrum of AIDS-related conditions and variations in associated inpatient mortality for AIDS patients treated in a national sample of hospitals. We identified 10,538 adult discharges with a diagnosis indicating AIDS from 258 hospitals from a national sample of 438 acute care hospitals with 6 million discharges in 1986-1987. Opportunistic and other infections occurred in 55.9 and 37.9%, respectively, of AIDS discharges, and inpatient fatality rates varied considerably depending on complication type(s) and comorbidities. Clinical conditions were more important predictors of inpatient death than demographic or treatment site characteristics. Among opportunistic infections, odds of inpatient death were significantly increased for progressive multifocal leukoencephalopathy (odds ratio [OR] = 2.8), Pneumocystis carinii pneumonia (OR = 2.4), cryptococcosis (OR = 1.6), atypical mycobacterial infections (OR = 1.6), and toxoplasmosis (OR = 1.3). Odds of inpatient death were also significantly increased by non-AIDS-defining infections causing septicemia (OR = 3.1) or CNS involvement (OR = 1.6) or pulmonary involvement (OR = 1.5). After controlling for clinical conditions, significant differences in odds of death persisted across regions, age, and ethnic groups. Increases in hospitals' AIDS treatment experience were associated with a significant decrease in odds of inpatient death. These analyses provide a national perspective on the diversity of AIDS-related clinical conditions and their relative effects on inpatient mortality. PMID- 1453328 TI - The significance of western blot assays indeterminate for antibody to HIV in a cohort of homosexual/bisexual men. The Multicenter AIDS Cohort Study. AB - The objective of this study was to determine the frequency and significance of nondiagnostic Western blot (WB) assays in homosexual/bisexual men at risk of infection with HIV-1. The presence of a positive enzyme-linked antibody assay (EIA) confirmed by a positive WB was used as evidence of infection and seroconversion. Indeterminate WB assays were defined as reactions to only one viral gene product of HIV-1. Three analyses were conducted to (a) determine the frequency of such reactions in men who, during a 4-year period, did not develop diagnostic serologic reactions; (b) determine, retrospectively, the preseroconversion frequency of indeterminate WB assays in 286 men who seroconverted; and (c) evaluate in vitro production of specific antibody by peripheral blood mononuclear cells (PBMCs) as a method of indicating whether or not an indeterminate WB assay represents HIV-1 infection. Reactions to products of gag, pol, or env were noted in 8.0, 4.0, and 6.7% of 1,595 first-visit tests of men who remained seronegative for 4 years. Indeterminate reactions occurred in 204 men with negative EIAs who subsequently seroconverted and in 82 men with positive EIAs preconversion. Supernatants harvested from PBMCs of 2 of 36 seroconverters obtained one or two visits preseroconversion and cultured with pokeweed mitogen were antibody-positive. All were positive at the visit, with diagnostic serology. None of the supernatants from cells of 19 men with EIA negative WB-indeterminate serologic assays were antibody-positive. Our results suggest that persistently EIA-negative homosexual/bisexual men who have indeterminate WB assays are unlikely to be infected with HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453329 TI - Inhibition of HIV-1 RNA production by the diphtheria toxin-related IL-2 fusion proteins DAB486IL-2 and DAB389IL-2. AB - Productive infection of cells by human immunodeficiency virus type 1 (HIV-1) is associated with the activation state of the cell and its obligatory expression of the interleukin-2 receptor (IL-2R), the latter providing a new target for antiviral therapy. A quantitative RNA-RNA hybridization assay is employed to detect production of HIV-1 RNA and to show that two IL-2 diphtheria toxin-related fusion proteins (DAB486IL-2 and its more potent, truncated form DAB389IL-2) inhibit HIV-1 RNA production in infected cells. A mutant form of DAB486IL-2 containing a single point mutation that inactivates the adenosine diphosphate ribosyltransferase activity of the toxin does not inhibit HIV RNA production, even though the molecule binds to the IL-2R. The active fusion proteins inhibit viral RNA replication in cells infected with HIV-1 clinical isolates as well as with a ZDV-resistant strain of HIV-1. These results indicate that IL-2 receptor targeted fusion proteins can be utilized to inhibit HIV-1 replication effectively in infected human lymphocytes. PMID- 1453330 TI - HIV-1 LTR activation model: evaluation of various agents in skin of transgenic mice. AB - Mice containing the HIV-1 long terminal repeat (LTR) regulating the expression of firefly luciferase reporter gene were investigated for their use as a model for activation of the LTR. As a limited test of this model, a number of different factors were screened for their ability to affect reporter gene activities in the skin. Reporter gene levels were increased in the skin by topical treatment of dimethylsulfoxide, retinoic acid, phorbol ester, ultraviolet light, and hydrogen peroxide, all of which have previously been shown to cause increased HIV production in cultured human cells. Topically applied arachidonic acid, histamine, ethanol, acetone, and methanol did not increase reporter gene activities. A lack of published reports on activation of HIV-1 in human cells by these agents suggests that they do not activate viral expression in human cells, which corroborates with the findings of this report. Minor forms of skin wounding and intraperitoneally administered psoralen plus ultraviolet light also increased reporter gene activities in skin. Control and test treatments could be performed on the same mouse and repetitive samples could be obtained from each treatment area. These transgenic mice might be useful as predictive models for regulation of the LTR in epidermal or dendritic cells. PMID- 1453331 TI - Longitudinal study of homosexual couples discordant for HIV-1 antibodies in the Baltimore MACS Study. AB - Thirty-six sexually active couples serologically discordant for human immunodeficiency virus, type 1 (HIV-1), within the Baltimore Multicenter AIDS Cohort Study (MACS) were assessed to determine whether evidence of HIV-1 infection could be detected in the HIV-1-antibody-negative partners and whether factors associated with lack of transmission of HIV from the seropositive to the seronegative partner could be ascertained. Six HIV-1 seropositive couples and 18 seronegative couples were followed concurrently for comparison. None of the seropositive subjects had an AIDS-defining illness at entry into the study, and all subjects were followed for 1 year. A separate evaluation of unprotected anal receptive and insertive intercourse between discordant couples indicated high risk activities for a median of 40 months, as reported by the HIV seropositive partner. Despite this finding, none of the HIV-1 seronegative men in discordant couples had evidence of HIV-1 infection by viral culture, p24 antigen testing, or polymerase chain reaction for HIV-1 DNA. Discordant seronegatives and seropositives did not differ from concordant seronegatives and seropositives in numbers of circulating CD4, CD8, and natural killer lymphocytes or in prevalence of antibodies to herpes simplex virus, type 1, Epstein-Barr virus, or cytomegalovirus, except that discordant seronegative men were less likely than their seropositive partners to have antibodies to herpes simplex virus, type 2. The reason for the apparent lack of HIV-1 infection in seronegative discordant individuals remains unexplained and did not appear to be associated with type of sexual activity, T-lymphocyte subsets or natural killer cells, or early stage of HIV-1 disease. PMID- 1453332 TI - A simplified surveillance case definition of AIDS derived from empirical clinical data. The Clinical AIDS Study Group, and the Working Group on AIDS case definition. AB - A clinical AIDS case definition is needed for surveillance in countries where the CDC case definition is not practical. To derive such a definition, we compared 110 HIV-seropositive and 135 randomly selected HIV-seronegative adult medical ward inpatients in Brazil. Multivariate analysis of clinical signs and symptoms and simple diagnoses resulted in a discriminant function with sensitivity of 89% and specificity of 96% in predicting for AIDS. These data were the empirical basis for a clinical definition of AIDS in adults drafted in a Caracas, Venezuela, workshop sponsored by the Pan American Health Organization. The revised "Caracas" definition presented here requires a positive HIV serology, the absence of cancer or other cause of immunosuppression, plus > or = 10 cumulative points, as follows: Kaposi's sarcoma (10 points); extrapulmonary/noncavitary pulmonary tuberculosis (10); oral candidiasis or hairy leukoplakia (5); cavitary pulmonary/unspecified tuberculosis (5); herpes zoster < 60 years of age (5); CNS dysfunction (5); diarrhea > or = 1 month (2); fever > or = 1 month (2); cachexia or > 10% weight loss (2); asthenia > or = 1 month (2); persistent dermatitis (2); anemia, lymphopenia, or thrombocytopenia (2); persistent cough or any pneumonia except TB (2); and lymphadenopathy > or = 1 cm at > or = 2 noninguinal sites for > or = 1 month (2). This definition has a sensitivity of 95% and a specificity of 100% (91% without HIV serology) when applied to the Brazilian patients in this study. The Caracas definition has been adopted by Brazil, Honduras, and Surinam, and is in validation elsewhere. The use of a reasonably sensitive and specific case definition commensurate with available diagnostic resources should facilitate AIDS surveillance in developing countries. PMID- 1453333 TI - HIV neutralization assay using polymerase chain reaction-derived molecular signals. AB - Characterization of the capacity of human polyclonal antibody to neutralize wild type patient isolates has important implications for vaccine development. We report the development of a polymerase chain reaction-based neutralization assay that quantitatively measures each infection using HIV proviral formation. These molecular end points identified the absence or quantitative diminution of DNA provirus formation as well as a delay in the kinetics of HIV DNA provirus formation. Using both laboratory strain prototype isolates (HIV-1-MN, HIV-IIIb) and primary wild-type patients' isolates, neutralization end points were reproducibly determined. End points were reached within 72 h, thereby minimizing the impact of subsequent rounds of infection on interpretation of results. Although the neutralization titer of polyclonal sera was usually comparable using standard technology, this assay did find isolate-dependent variation in the relationship between p24 production and HIV proviral DNA formation. Finally, we noted the disparity between the ability of human sera to neutralize prototype and wild-type isolates in primary peripheral blood mononuclear cell targets. We believe this assay provides unique opportunities to characterize the initial events of virus-antibody interaction and will help to elucidate clinically relevant neutralization immunoregulatory mechanisms. PMID- 1453334 TI - Drug hypersensitivity reactions and human immunodeficiency virus disease. AB - Drug hypersensitivity reactions are often observed by clinicians treating patients infected with the human immunodeficiency virus (HIV). For certain drugs, the incidence of these reactions appears to be higher than previously reported in the general population. The best example is trimethoprim-sulfamethoxazole, associated with rash, fever, hematologic disturbances, transaminase elevation, and, less frequently, more severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylactic-like reactions. Other sulfa congeners, pentamidine, antituberculosis regimens containing isoniazid and rifampin, amoxicillin-clavulanate, clindamycin, and thalidomide also have been associated with an increased incidence of adverse reactions, some of which could involve allergic mechanisms. Effective dosage and management strategies are needed to prevent or ameliorate hypersensitivity reactions when they occur. PMID- 1453335 TI - Tumor necrosis factor-alpha in advanced HIV infection in the absence of AIDS related secondary infections. AB - The effect of HIV infection on the production of tumor necrosis factor-alpha (TNF alpha) was examined in patients with advanced human immunodeficiency virus (HIV) infection in the absence of AIDS-related secondary infections. Serum TNF-alpha and TNF-alpha production in vitro were measured by enzyme-linked immunosorbent assay in 26 male homosexuals with CDC stage IV HIV infection without active AIDS related secondary infections. In vitro TNF-alpha production was assayed from cultured peripheral blood mononuclear cells (PBMs) or whole blood cultures under conditions for minimising endotoxin contamination. PBMs and whole blood were cultured with and without lipopolysaccharide (LPS). Results were compared with those for 13 HIV-seronegative age- and sex-matched controls. Serum TNF-alpha concentrations were 5 +/- 16 pg/ml in HIV-infected patients and 12 +/- 17 pg/ml in controls. TNF-alpha levels in unstimulated cultures of PBMs obtained from patients were 426 +/- 511 pg/ml and 456 +/- 428 pg/ml in control cultures. There was no difference between groups in the maximal responses of cultured PBMs to stimulation with LPS (2,229 +/- 1,593 pg/ml vs. 2,504 +/- 961 pg/ml). TNF-alpha levels from unstimulated and LPS-stimulated whole blood cultures were not significantly different after adjusting for the number of cultured monocytes (2,038 +/- 1,469 pg/ml vs. 1,511 +/- 488 pg/ml). In 10 patients (38%) the TNF alpha levels from stimulated whole blood cultures were greater than the 95% confidence interval of the control group. TNF-alpha levels in patients were not significantly altered by antiretroviral therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453336 TI - Infectivity of retroviral DNA in vivo. PMID- 1453337 TI - Can HIV-1 infection be transmitted by a "discarded" syringe? PMID- 1453338 TI - Prevalence of HTLV-I/II among blood bank donors in Argentina. PMID- 1453339 TI - Survival differences for 547 AIDS cases in Milan. PMID- 1453340 TI - Results of the 1992 journal of Post Anesthesia Nursing readership survey. PMID- 1453341 TI - The visiting needs of critically ill patients and their families. AB - The purpose of this article is to provide an overview of completed studies that consider visitors in critical care areas. Studies from coronary care, intensive care, pediatric PACUs, and adult PACUs are reviewed. PMID- 1453342 TI - Comparison of nurses' and family members' perceived needs during postanesthesia care unit visits. AB - Today, more PACUs are opening their doors to visiting family members. This change can be exciting and challenging for the PACU nurse. The expertise involved when caring for the patient must be also extended to the family. Literature shows that families have identifiable needs. By attending to those needs, the nurse may help decrease stress for the family during the patient's hospitalization and enable everyone to cope more effectively. Limited published research is available regarding the needs of family members of PACU patients. This descriptive study explores and compares needs identified by family members when visiting PACU patients with needs of these family members perceived by PACU nurses. Analysis of data using the Mann Whitney-U Test indicates a significant difference between the groups. PACU nurses believed that family members' most important need was information. Family members stated that the need to see the family member was more important than was perceived by the nurses. Both groups agreed that education was an important need. Further studies using a larger sample are needed to validate findings of this study. PMID- 1453343 TI - Alternate methods of teaching: use of self-learning packets. AB - Self-directed learning takes multiple forms, all of which allow a person to study at an individual pace and direction. By applying principles of adult learning and various other styles of learning, self-directed learning can be used as an alternative method of education. The focus of this article is one type of self directed learning, self-learning packets. The step-by-step process of designing a self-learning packet is covered. Various methods of topic selection and the key components of self-learning packet design are included. Finally, the usefulness of alternative methods of education such as self-learning packets is examined by cost analysis. PMID- 1453344 TI - The use of temperature as a discharge criterion for ambulatory surgery patients. AB - Evaluating each patient's return to an acceptable state after surgical and anesthetic intervention is the responsibility of the postanesthesia nurse. Postanesthesia nurses use criteria to determine ambulatory surgical patient readiness to be discharged from phase I recovery to phase II recovery and from phase II recovery to home. Temperature is one indicator of postanesthesia recovery. Temperature discharge criteria from phase I postanesthesia recovery have been reported. However, temperature discharge criteria for phase II postanesthesia recovery have been adapted from phase I standards and nursing traditions. This study sought to describe the postoperative temperatures of ambulatory surgical patients from admission to phase II postanesthesia recovery to discharge home. A convenience sample of 101 adult patients undergoing surgery at a hospital-based ambulatory surgical unit (ASU) participated. Tympanic temperature was measured preoperatively on admission to the ASU, postoperatively, at the beginning of phase II postanesthesia recovery, and at the end of phase II postanesthesia recovery immediately before discharge home. All subjects were normothermic during phase II postanesthesia recovery, with temperatures ranging from 36.0 degrees C (96.8 degrees F) to 38.3 degrees C (101 degrees F). Paired Student's t Test showed significant differences (P < .0001) between temperature means. There was a 0.38 degrees C (0.7 degree F) decrease between preoperative admission temperature and temperature on admission to phase II postanesthesia recovery. During phase II postanesthesia recovery the mean temperature increased 0.16 degree C (0.3 degree F) before discharge home. However, the clinical and practical implications of these findings is questionable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453345 TI - Practical points in the care of the patient post-thyroid surgery. AB - It is the purpose of this article to discuss the care of the patient after thyroid surgery. Preoperative preparation will be presented, thyroid anatomy reviewed, and surgical interventions identified. PACU care of the patient identifies specific patient priorities and potential postoperative complications. PMID- 1453346 TI - Instrument development: writing the items. AB - An important step in instrument development is writing the items that are derived from concept analysis and validation. It is also important to determine if the instrument is to be constructed for criterion-referenced or norm-referenced measurement; examples for both are discussed. Also discussed are methods for developing a blueprint for a psychosocial instrument. Additional methods presented are how to construct the items as simple rather than complex sentences, to keep the sentences short and unambiguous, and to construct the items for an eighth-grade reading level to facilitate patient use. PMID- 1453347 TI - Managers, monkeys, and mind-set. AB - One of the most difficult things for a manager to learn is effective time management. The challenge seems to be one of learning what tasks really should be done by the manager and what really can and should be delegated to the staff. This article provides some guidance to managers as they make those decisions. PMID- 1453348 TI - New opportunities for Americans with disabilities. AB - Historically, individuals with disabilities have been isolated and segregated. Physical and psychological barriers left them significantly disadvantaged, politically powerless, and without legal recourse in matters of discrimination. The Americans With Disabilities Act of 1990 is opening doors and promising new opportunities for individuals with disabilities to contribute and participate fully in our society. The author offers an overview of the purpose and major provisions of the act, which compares in scope to the Civil Rights Act of 1964. PMID- 1453349 TI - [Use of semi-quantitative approaches in the evaluation and classification of potential teratogenicity of industrial poisons]. AB - To provide a consistent teratogenic risk assessment from animals' data, the system described here suggests an evaluation by stages. Based on the expert system from Mattison, the toxic responses of common species of experimental animals are scored. The scores are then multiplied by the ratio of the lowest adult 'toxic dose A, to the lowest developmental toxic dose D (A/D). The products form 3 categories. Based on the reversibility of the developmental effects, the categories are subdivided into classes A B C D. This system should permit an unbiased risk assessment and a comparison of industrial chemicals' prenatal toxicity. PMID- 1453350 TI - [Toxicity of chloroform and vitamin A status in the rat]. AB - After a chloroform intraperitoneal injection, lactate dehydrogenase, alanine aminotransferase and particularly aspartate aminotransferase serum activities are much more raised in deficient animals. Liver ornithine decarboxylase (ODC) activity normally decreases in rats between the 4th. and the 7th. month after the weaning. In vitamin A deficient animals, basal values of the enzyme activity are lower and the decrease is deeper. But even at month 7, liver sustains a partial capacity of ODC recovery if retinol is fed during 15 days. Chloroform administration strongly enhances liver ODC activity in normal rats. In the deficiency, stimulation is lower in absolute value but relatively higher if referred to basal level. After retinol refeeding, chloroform stimulates enzyme activity to nearly normal values. Vitamin A deficiency impairs obviously liver ODC activity and its response to chloroform stimulation in rats, but the stroke is at least partially reversible in our conditions. Moreover, deficient animals maintain a non negligible capacity of ODC response under chloroform stimulation. PMID- 1453351 TI - [Teratogenic action of alpha-asarone in the mouse]. AB - The embryotoxicity and teratogenicity of alpha-asarone were investigated in mice. The drug was dissolved in corn oil, and administered daily, by gavage, on days 6 to 15 of gestation, at 0 (controls), 5, 15, 30 and 60 mg/kg. Fetuses were removed on day 18 by caesarean section and examined using routine teratological methods. A significant maternal toxicity was observed in dams given 60 mg/kg, as indicated by a reduced weight gain. An embryolethality was observed in 15, 30 and 60 mg/kg treated groups. In addition, the highest dose induced fetal malformations, mainly represented by hydrocephaly, extra-ribs, clubfeet and cleft lips. PMID- 1453352 TI - [Effects of environmental tobacco smoke on prenatal development. (Review of the medical literature)]. AB - For near thirty years, epidemiological studies have coped with the search of possible noxious consequences of an involuntary exposure of pregnant women to environmental tobacco smoke on the gestation and the intrauterine development of embryo and foetus. These studies were mainly retrospectives; a careful study of the methods used (questionnaires, evaluation of exposure, and so on ...) gives evidence that they can rarely avoid serious criticism. As possible effects of intrauterine exposure to environmental tobacco smoke, low birth weight and impairing of other body parameters, perinatal mortality, frequency of abnormalities have been reviewed. As a potential cause, the role of the father tobacco smoking has been especially examined. As a whole, the consequences of a prenatal exposure to environmental tobacco smoke are an extremely controversial subject and no obvious effect has yet been universally recognized. The critical analysis of the studies has shown that, frequently, the epidemiological studies have been interpreted in order to find links between and involuntary exposure to tobacco smoke and some troubles of reproduction, particularly in offspring. As a matter of facts, fundamentally, the noted actually correlations, even if they are statistically significant, are not able to move such links. They are only able to indicate the existence of an association and only, if the eventual role of confounding factors has been properly treated. An interesting case is the potential effects of the father's tobacco smoking. The hypotheses emerging from these examined inquiries remain to be more precisely defined and thoroughly by new studies, preferentially prospective, and, when necessary, completed by animal experiments. It is suggested that a special effort shall be applied to the measurement of the exposure of pregnant women to define toxic compounds originating from environmental tobacco smoke. Presently, it is not possible to draw a conclusion on the noxious or innoxious influence of the involuntary exposure of pregnant women to environmental tobacco smoke, particularly as far as potential risks for foetus are concerned. PMID- 1453353 TI - An assessment of proteolytic enzymes in Tetrahymena thermophila. AB - Cellular extracts of Tetrahymena thermophila were found to contain substantial levels of proteolytic activity. Protein digestion occurred over broad ranges of pH, ionic strength, and temperature and was stimulated by treatment with thiol reductants, EDTA and sodium dodecyl sulfate. Incubation at temperatures > or = 60 degrees C or with high concentrations of chaotropic reagents such as 10 M urea or 6 M guanidine-HCl caused an apparent irreversible loss of activity. Activity was also strongly diminished by increasing concentrations of divalent cations. Several peptide aldehydes, p-hydroxymercuribenzoate, and alkylating reagents such as iodoacetate, N-tosyl-L-lysine chloromethyl ketone, N-tosyl-L-phenylalanine chloromethyl ketone, N-methylmaleimide, and trans-epoxysuccinyl-L-leucylamido-(4 guanidino)-butane were potent inhibitors of proteolytic activity. Aprotinin diminished activity by approximately 40% while benzamidine, 3,4 dichlorosocoumarin, and trypsin inhibitors from soy bean, lima bean, and chicken egg caused relatively modest inhibition of proteolytic activity. Phenylmethanesulfonyl fluoride had no apparent effect. Electrophoretic separation of proteins on SDS-polyacrylamide gels copolymerized with gelatin substrate revealed that at least eight active proteolytic enzymes were present in cell extracts ranging in apparent molecular weight from 45,000 to 110,000. Five of these apparent proteases were detected in 70% ammonium sulfate precipitates. Gelatinase activity was not detectable when extracts were pretreated with iodoacetate or E-64, indicating that all of the enzymes observed in activity gels were sensitive to thiol alkylation. Cellular extracts of T. thermophila appeared to contain multiple forms of proteolytic enzymes which were stimulated by thiol reductants and inhibited by thiol modifying reagents. Accordingly, the proteolytic enzymes present in cell extracts appear to be predominantly cysteine proteinases. PMID- 1453354 TI - Electron microscopic analysis of circumsporozoite protein trail formation by gliding malaria sporozoites. AB - Immunoelectron microscopic techniques were utilized to characterize the morphology of circumsporozoite protein-containing trails deposited on various substrates by gliding Plasmodium berghei and Plasmodium falciparum sporozoites. The basic components of the trails are beadlike particles, 25 to 90 nm in diameter, which are devoid of unit membrane and have an electron-lucent center. Trails were captured on formvar-covered grids coated with anticircumsporozoite protein monoclonal antibodies and compared with trails produced on uncoated formvar; the results suggest that material containing circumsporozoite protein forms the matrix within which the particles are embedded. The trails exhibit morphological features similar to those displayed by circumsporozoite precipitation reactions; of note is the demonstration of sheaths of circumsporozoite protein-containing material that emanate from sporozoites prior to their gliding. The sheaths narrow into accumulations of electron-dense material, which eventually taper to form typical trails. The structural manifestation of sheaths and other morphological details of the formed trails enables us to correlate sporozoite behavior during trail formation with the motile actions of gliding sporozoites observed by light microscopy. PMID- 1453355 TI - Lysosomal membrane proteins of Amoeba proteus, as studied with monoclonal antibodies. AB - Monoclonal antibodies were prepared against lysosomal membrane proteins of amoebae and used to follow lysosome-phagosome fusion after induced phagocytosis. The specificity of antibodies was checked by indirect immunofluorescence microscopy, immunoelectron microscopy, and localization of the antigen in subcellular fractions. The antibody-recognized proteins started to appear on the membranes of phagolysosomes about 5 min after phagocytosis as detected by indirect immunofluorescence, and the intensity of fluorescence increased for up to 1 h. Results of injection experiments in which purified antibodies had been injected into living cells and probed by indirect fluorescence indicated that the antigens were located on the cytoplasmic side of the lysosomal membranes. Lysosomes fuse with phagosomes on the one hand but not with non-fusible vesicles such as symbiosomes on the other. The results support the view that a membrane component(s) of non-fusible vesicles somehow prevents lysosomes from fusing with them. PMID- 1453356 TI - Micronuclear DNA from Paramecium tetraurelia: serotype 51 A gene has internally eliminated sequences. AB - A method for the isolation of micronuclear DNA from Paramecium tetraurelia has been developed. After cell lysis, a low speed centrifugation at 1,000 g is used to remove all of the unbroken cells and macronuclei and approximately two thirds of the macronuclear fragments. Next a higher speed centrifugation of 9,000 g sediments the micronuclei and frees them from small particulates and soluble constituents. Advantage is then taken of the fact that micronuclei have a lower density than do macronuclear fragments in 45%-60% Percoll. Micronuclei float to the top during centrifugation at 24,000 g, while macronuclear fragments sediment. After several cycles of centrifugation in Percoll, the micronuclei, although heavily contaminated with cytoplasmic components, are essentially free of macronuclei and macronuclear fragments. Micronuclear DNA can then be extracted from the suspension. The whole procedure is very rapid and in about an hour micronuclear and macronuclear DNA can be separated. About 2 micrograms of micronuclear DNA can be obtained from 6 x 10(7) paramecia. We find that there are internal sequences in the micronuclear A gene DNA in wild type cells which are eliminated when the micronuclei develop into macronuclei. They yield unique restriction fragments for micronuclei and macronuclei. Therefore the purity of the preparations is easily monitored by probing Southern blots of restriction enzyme-digested DNA with the cloned A gene. No differences have been found between the micronuclear A gene in wild type and the d48 mutant. PMID- 1453357 TI - Meiosis-reinitiation-inducing factor of Tetrahymena functions upstream of M-phase promoting factor. AB - Reinitiation of meiosis (maturation) of amphibian Bufo and Xenopus oocytes can be induced if Tetrahymena extract is injected into them. The activity differed from M-phase-promoting factor, because action of the former factor on the induction of maturation was inhibited by treatment of the oocytes with cycloheximide. Activity of M-phase-promoting factor was not detected in Tetrahymena extract regardless of the presence of cdc2 homologues in the extract. However, cycloheximide-resistant maturation-inducing activity appeared in the recipients, when the maturation was induced by injection of Tetrahymena extract. Immunoblots using antibodies against cdc2 showed that injection of Tetrahymena extract induced fast mobility of the recipient cdc2 in the presence of the recipient protein synthesis. The same mobility shift of the cdc2 was also induced when M-phase-promoting factor containing Xenopus oocyte extract was injected into immature oocytes or when the immature oocyte extract was treated with alkaline phosphatase. These results indicate that meiosis-reinitiation-inducing factor of Tetrahymena functions upstream of M-phase-promoting factor to induce dephosphorylation of the recipient cdc2. Tetrahymena cdc2 homologues also showed fast mobility when the Tetrahymena extract was treated with alkaline phosphatase. Preliminary experiments showed that the meiosis-reinitiation-inducing factor of Tetrahymena was a soluble protein. PMID- 1453358 TI - Sporogonic development of Leucocytozoon smithi. AB - The sporogonic development of Leucocytozoon smithi in its black fly vector was studied by light and electron microscopy and was compared with that of other haemosporidians. Within 18 to 24 h after ingestion of gametocytes by black flies, ookinetes passing through the midgut epithelium were observed. Intracellular migration of ookinetes resulted in the apparent disruption and degeneration of host cells. Intercellular migration also occurred as was evidenced by the presence of ookinetes between midgut cells. Transformation of ookinete to spherical oocyst occurred extracellularly in three different sites. Although most oocysts were found between the host cell basal membrane and the basal lamina, large numbers also were found attached to the external surface of the basal lamina, projecting into the hemocoel. Ectopic development of oocysts in the midgut epithelium between cells was observed much less frequently than development on the basal side of the midgut. The oocyst wall of dense granules, believed to be of parasite origin, was distinguishable from the basal lamina of the host's midgut epithelium. As in other Leucocytozoidae, the cytoplasm of the oocyst differentiated into a single sporoblastoid from which 30-50 sporozoites were formed. Beginning on the third day post infection, elongation of segregated dense sporoblastoid material associated with pellicle thickening led to the formation of the finger-like sporozoite buds which projected into the oocyst cavity. Sporozoites within mature oocysts and salivary glands were structurally similar to sporozoites as described for other haemosporidians. PMID- 1453359 TI - Experimental horizontal transmission of Enterocytozoon salmonis to chinook salmon, Oncorhynchus tshawytscha. AB - Enterocytozoon salmonis was transmitted to chinook salmon Oncorhynchus tshawytscha by feeding tissues infected with the parasite and by cohabitation of noninfected fish with experimentally infected fish. Affected fish (dead and survivors) in both transmission trials had gross and microscopic signs of the disease and merogonic and sporogonic stages of the parasite. There were no morbidities or mortalities, or evidence of the parasite among control fish in either study. Results suggest that the parasite may be contracted by indirect contact among healthy and infected fish held in crowded ponds or net pens or by direct ingestion of spores found in the water. PMID- 1453360 TI - Discontinuous genetic variation among mesophilic Naegleria isolates: further evidence that N. gruberi is not a single species. AB - Naegleria isolates which are currently placed in the type species N. gruberi display great genetic, physiological and morphological heterogeneity. There are two possible interpretations of the nature of this species--that N. gruberi is a species complex or that it is a single continuously variable species. To distinguish between these alternatives, allelic states were determined for 33 loci in 74 new isolates selected to represent wide geographic sources and diverse temperature limits for growth. The results were compared with data for culture collection strains of N. gruberi and other species in the genus. The isolates formed a discontinuous series of clusters, separated by genetic distances similar to those separating the better-characterised taxa N. fowleri, N. lovaniensis, N. jadini, N. australiensis australiensis and N. australiensis italica. Culture collection strains assigned to N. gruberi fell into six distinct clusters, while other clusters were not represented by reference strains. The data are most consistent with the interpretation that N. gruberi is a group of several distinct species, each equivalent to the recently described species in the genus. Naegleria andersoni andersoni and N. andersoni jamiesoni also formed two distinct clusters, equivalent to species. Characteristics temperature limits for growth show that the mesophilic species are ecological as well as genetic entities. PMID- 1453361 TI - Immobilization antigens from Tetrahymena thermophila are glycosyl phosphatidylinositol-linked proteins. AB - We have studied four strains of Tetrahymena thermophila, each of which expresses a different allele of the SerH gene and produces a distinctive surface protein of the immobilization antigen (i-antigen) class. Following exposure of the strains to [3H]ethanolamine or [3H]myristic acid, a protein corresponding in molecular mass to the characteristic i-antigen for that strain became highly labeled, as determined by mobility in sodium dodecylsulfate-polyacrylamide electrophoresis gels. Furthermore, antibodies raised to the i-antigens of the T. thermophila strains selectively immunoprecipitated radioactive proteins having molecular mass identical to that of the i-antigen characteristic for that particular strain. The lipid moieties labeled by [3H]myristate were not susceptible to hydrolysis by exogenous phosphatidylinositol-specific phospholipase C from bacteria. However, when protein extraction was carried out in the absence of phospholipase C inhibitors, radioactive fatty acids derived from [3H]myristate were rapidly cleaved from the putative i-antigens. On the basis of available data, it was concluded that T. thermophila i-antigens contain covalently-linked glycosyl phosphatidylinositol anchors. PMID- 1453363 TI - A general practice trainee in Kurdistan. PMID- 1453362 TI - Case report: a case of rectal perforation by foreign body presenting as pyrexia of unknown origin. PMID- 1453364 TI - Advanced Trauma Life Support aboard RFA Argus. AB - The Advanced Trauma Life Support (ATLS) system was adopted for casualty reception and resuscitation. ATLS permitted well-informed triage decisions to be made, coupled with appropriate initial, possibly life-saving, treatment. The training given on board has continued to benefit patients treated by ex-Argus staff in their peacetime roles. PMID- 1453365 TI - An insight into the life of Royal Naval surgeons during the Napoleonic War. Part 2. PMID- 1453366 TI - The Knee Signature System: a preliminary report. PMID- 1453367 TI - Dura and cranial base reconstruction by external oblique fascia and rectus abdominis muscle flap. AB - The rectus abdominis muscle flap, combined with the external oblique fascia, were utilized in cranial-base reconstruction. In a wide defect caused by resection of a giant meningioma, the dura was reconstructed with the external oblique fascia and anterior sheath, and the cranial-base defect was reconstructed with the rectus abdominis muscle flap. PMID- 1453368 TI - Reconstruction of recurrent pressure sores using free flaps. AB - The authors describe two successful reconstructions of recurrent pressure sores with free fasciocutaneous flaps. In Case 1, a free lateral thigh flap pedicled on the first and third direct cutaneous branches of the deep femoral vessels was used to cover a large recurrent sacral pressure sore. The vascular pedicle was dissected to the deep femoral trunk proximally and anastomosed to the inferior gluteal vessels. In Case 2, a free medial plantar flap was transferred to a recurrent ischial pressure sore. The vascular pedicle was dissected to the posterior tibial vessels proximally. The long vascular pedicle of the flap was passed through the femoral subcutaneous tunnel, and end-to-side microvascular anastomoses were performed to the superficial femoral trunk without any vein grafts. The authors advocate the use of free tissue transfer for recurrent pressure sore reconstruction. PMID- 1453369 TI - Cryopreserved allogeneic vessel and nerve grafts: hind-limb replantation model in the rat. AB - The authors have previously reported the permanent storage of skin and cutaneous flaps using cryopreservation. In this study, replantation of the hind limb was performed in rats, using an allogeneic femoral artery, vein, and sciatic nerve which had been cryopreserved for more than 3 weeks. Femoral arteries, veins of 2 cm in length, and sciatic nerves of 1.5 cm in length from Lewis rats were cryopreserved for more than 3 weeks to decrease antigenicity. The hind limb of a Brown Norway rat was completely amputated at its mid-length and the cryopreserved artery, vein, and nerve were interposed in the anastomosis of the femoral artery, vein, and sciatic nerve. Immunosuppressants were not used. Hind limbs were replanted in six rats, and all cases survived. Toe spread and gait-foot analysis revealed good results at 3 months postoperatively. Excellent axonal regeneration was observed in the pathologic examination of the sciatic nerve 1 cm distal to the transfer. This report introduces a long-term storage method for vessels and nerves and extends the possibilities for clinical use of cryopreserved vessels and nerves, using replantation in a rat model. PMID- 1453370 TI - Successful replantation of the lower leg after 42-hour ischemia: case report. AB - A case of right lower-leg replantation after 42-hr ischemia is presented. Revascularization of the other foot with circulatory decompensation after 36-hr ischemia was carried out simultaneously. The replanted lower leg survived. Following its shortening in replantation by 12 cm, right lower-leg lengthening by 8 cm was carried out 1.5 years after replantation with the aid of a distraction apparatus. The locomotor function in both lower extremities recovered. PMID- 1453371 TI - Successful digital replantation after 42 hours of warm ischemia. AB - Previously, 6 to 10 hr were believed to be an acceptable limit of warm ischemia for successful digital replantation. The longest warm ischemia time ever reported was 33 hr. This report presents successful replantations of two fingers after 42 hr of warm ischemia. PMID- 1453372 TI - Secondary coverage of the hand using a dorsalis pedis plus first web space free flap. AB - Traditionally, severe degloving injuries of the hand have been treated with random abdominal or pedicled groin flaps, which offer good cutaneous coverage but do not provide sensibility. The authors present the results of the application of an extended dorsalis pedis plus first web space of the foot flap to resurface the hands of five male patients who had been treated originally with random abdominal or pedicled groin flaps. The reported flap has the advantage of providing the patient with up to three different nerve territories, aiding in a better functional use of the hand. PMID- 1453373 TI - Reinnervated radial forearm free flaps in head and neck reconstruction. AB - The radial forearm flap has proved to be a reliable free flap for intraoral reconstruction after major head and neck ablative surgery for cancer. In contrast to the myocutaneous flap, it is thin and flexible, and as a result, it is better suited to conforming to the irregular surface which remains over an intact or restored mandible. A criticism of both techniques however, is that while the flap effectively fills the defect, it serves as an insensate reservoir in which food and saliva can collect. A modification of the reinnervated radial forearm free flap is presented, with discussion of its use in three patients, following extensive resection of the floor of the mouth and tongue. PMID- 1453374 TI - Morphologic characteristics of muscles grafted in rabbits with neurovascular repair. AB - In 34 female white rabbits, rectus femoris (RFM) muscles were grafted with immediate anastomoses of the vasculature (VA) and with nerves either left intact (NI-VA) or with nerves repaired (NR-VA). The purpose of the study was to compare the morphologic changes that occur in NI-VA grafts and NR-VA grafts from 8 to 120 days after grafting. After 8 days, nearly complete survival of all muscle fibers was found. The muscle mass and single fiber cross-sectional area (CSA) of the NI VA group remained near control values for the first 30 days and then declined to 82 percent and 62 percent of the control values, respectively. Little evidence of morphologic disruption was observed. The NR-VA grafts displayed a significant denervation atrophy within the first 15 days, with relative values 67 percent of the control value for mean mass and 53 percent for single fiber CSA. By 120 days, mass and CSA recovered to 80 percent and 62 percent of control values. Although the similarity of the deficits in the nerve-intact and nerve-repaired grafts suggest that tenotomy and repair, rather than innervation, were the major limitations, the mechanism was not resolved. PMID- 1453375 TI - A simple cuff-suture technique for microvascular anastomosis. AB - The use of synthetic cuffs to simplify and hasten microvascular anastomoses is offered as an alternative to conventional methods. In this study, a soft, non irritating, silicone rubber cuff was used to construct end-to-end and end-to-side cuff-sutured anastomoses in rats. This technique was as rapid as other non sutured anastomoses, required no assistant, and provoked no foreign-body reactions. PMID- 1453376 TI - Leukocyte adhesion to vascular endothelium. AB - Leukocyte adhesion and emigration are controlled by soluble mediators and effected by various adhesion molecules. Currently, three major families of adhesion receptors are known to contribute to this process: integrins, vascular selectins, and immunoglobulin-like receptors. These adhesion systems are not additive and mutually replaceable, but appear to constitute a cascade of events. Leukocyte margination is followed by rolling, firm adhesion, emigration, and migration in the interstitial space. In addition, biomechanical parameters like leukocyte deformability and shear stress exerted by the flowing blood modulate the efficacy of adhesive interaction. This article briefly reviews the molecular nature, biologic regulation, and physiologic function of pertinent adhesion receptors. PMID- 1453377 TI - Exercise induced injuries--the way ahead. PMID- 1453378 TI - Smoking impairs the response to a physical training regime: a study of officer cadets. AB - One hundred and sixty five officer cadets completed a 6 month physical training programme; 47 (28%) were smokers and 118 (72%) were not. Improvements in fitness were measured by the Army Personal Fitness Assessment (APFA) which scores for both strength and endurance. Initially both groups had similar APFA scores [mean (SEM)]: smokers 114 (3.1), non smokers 120 (2.3), difference not significant. Six months later both groups had improved their scores: smokers 131 (2.7), non smokers 143 (2.3), but the smokers were now significantly less fit (p < 0.01). The British Army needs a more effective anti smoking policy as 50% of young soldiers continue to smoke, and have an increased risk of premature ischaemic heart disease when compared with their civilian counterparts. Physical fitness remains important in the Army and evidence such as this may help persuade soldiers to give up smoking before standard tests of cardiovascular or lung function show any abnormalities, with benefits for the future health of the Army. PMID- 1453379 TI - A new chart to assist with advanced trauma life support. AB - Many studies have drawn attention to deficiencies in the management of major trauma, both in the UK and elsewhere. One area that has received little attention is the documentation of such cases in the Emergency Room. When outcome may be sub optimal, documentation assumes greater importance if advances are to be made in the organisation of trauma care. Based upon the American College of Surgeons Advanced Trauma Life Support (ATLS) protocols, the authors have designed a document that records dynamically what happens to the multiply injured victim on arrival in the Emergency Room. It unifies the recording of vital signs, whilst acting as an assessment and resuscitation template. By ensuring no life threatening illness is missed it is likely to improve patient survival. The document can act as a basis for teaching and a medico-legal record, whilst providing the necessary data for quality assurance and outcome audit. PMID- 1453380 TI - Chronic pancreatitis in the British Army 1978-1989. AB - A retrospective study was made of all 28 soldiers with chronic pancreatitis first diagnosed between 1978 and 1989. All patients were male, alcohol was the aetiological factor in 90%, the mean age at diagnosis was 30 and the commonest mode of presentation was with recurrent painful episodes of pancreatitis. Endocrine and exocrine pancreatic insufficiency occurred in a quarter and a third of patients respectively and one third required surgical intervention. PMID- 1453381 TI - Experiences in a level-1 trauma centre. PMID- 1453382 TI - A case of factitious fever and 'epilepsy'. AB - We describe the case of a 23 year old male who presented with a history of intermittent pyrexia associated with apparent episodic loss of consciousness. During these events, thermometers placed in the rectum and axillae supported the elevated oral temperature readings. After numerous investigations including electroencephalography had excluded organic disease, the patient was observed applying a hot douche to his rectum prior to his temperature being recorded. PMID- 1453383 TI - Complications of prophylactic intercostal tube drainage--including tension pneumothorax. AB - A case is presented of tension pneumothorax associated with intercostal tube drainage. Complications of intercostal tube drainage are reviewed. PMID- 1453384 TI - The corps disease: brucellosis and its historical association with the Royal Army Medical Corps. AB - Brucellosis (also known as Malta, Mediterranean or Undulant Fever) has aptly been nicknamed the Corps Disease because of the major role played by the Royal Army Medical Corps in elucidating its nature and discovering its mode of spread, thus leading to its prevention and eradication. This history of brucellosis, incorporating a complete bibliography of all references to the disease in the Journal of the Royal Army Medical Corps from 1903 to 1992, documents the fascinating story of this association. PMID- 1453385 TI - Battlefield surgical care--lest we forget. PMID- 1453386 TI - Leptospirosis. PMID- 1453387 TI - Leptospirosis--a cause for concern? PMID- 1453388 TI - Post-operative wound infections in Belize. PMID- 1453389 TI - The number of cells used for immunotherapy of repeated spontaneous abortion influences pregnancy outcome. AB - One hundred and sixty-eight women were immunized on a single occasion with paternal mononuclear cells (MNC) for recurrent spontaneous abortion (RSA) and pregnancy outcomes were analysed with respect to the number of MNC given. The study was done in a prospective sequential fashion using all MNC recoverable from a unit of the spouse's blood and both patients and investigators were blinded as to the number of cells injected. Women receiving low and mid-range doses of MNC (58-305 x 10(6) and 308-567 x 10(6), respectively) had a significantly higher pregnancy success rate (57%) than those receiving the high (568-2677 x 10(6)) dose of MNC (41%). In 77 consecutive patients the diameter of the largest immediate skin flare reaction at the site of subcutaneous injection was recorded. No correlation was found between the skin flare response and the number of MNC injected. Our data suggest that a blinded trial of paternal MNC immunization comparing what appears to be optimum numbers of cells (100-550 million) to a low dose inoculum (e.g., 10 million), again noting the sizes of the skin flare reactions, might answer questions about efficacy and placebo effects of immunotherapy for RSA. PMID- 1453390 TI - Differential distribution of interleukin-1 alpha and interleukin-1 beta proteins in human placentas. AB - Interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) were identified in samples of first trimester and term placentas by immunocytochemistry using two sets of polyclonal antibodies to recombinant IL-1. All samples contained the two species of IL-1, which predominated in different types of cells: IL-1 alpha was contained primarily in placental villous trophoblastic and stromal cells whereas IL-1 beta was localized to cells in fetal and maternal blood. With respect to the cellular localization of the two proteins, early and late gestation tissues were similar. Although these results were generally consistent for the two sets of antibodies, differences were noted in the binding patterns of the individual reagents. The findings in this study provide strong support for the postulate that IL-1 modulates placental development and suggest that IL-1 alpha may be the preferred species in extraembryonic tissues. PMID- 1453391 TI - Distribution of lymphocyte subsets in rat milk from normal and Trichinella spiralis-infected rats. AB - We have shown that T. spiralis-specific T lymphocytes can mediate maternal-to neonatal immunity during lactation. This study addresses the change of lymphocyte populations in rat milk during normal and disease conditions. Two color flow cytometric analysis was performed for milk lymphocytes. T cells (OX19+) made up 45% of rat milk lymphocyte population. T helper cells (Th) composed 35% of total T cells while T cytotoxic/suppressor (Tcs) cells constituted 34%, giving a Th/Tcs ratio of 1.03. The corresponding ratio Th/Tcs in peripheral blood was 2.8. Approximately 21% of OX8+ cells in rat milk were OX19- natural killer (NK) cells. When using the monoclonal antibody 3.2.3 (NKR-P1), 43% of lymphocytes in control rat milk and 14% of blood lymphocytes were NK cells. This indicates a selective passage of these cells into milk. In T. spiralis-immunized rats, the percentage of total T cells was slightly decreased; however, Th and Tcs cells were consistent as compared to control milk. The percentage of NK cells (OX8+OX19-) in milk from T. spiralis-immunized rats was significantly higher than that from control milk (65% vs. 21%, respectively, P less than 0.01). This result was confirmed using the monoclonal antibody 3.2.3 which showed that milk from immunized rats contained 63% NK cells compared to 43% in normal milk (P less than 0.01). This study suggests that NK cells are selectively passaged into rat milk and T. spiralis infection induces an increase of NK cells in milk. PMID- 1453392 TI - Antifertility effects of antisperm cell-mediated immunity in mice. AB - C57BL/6 female mice were immunized with allogeneic (DBA/2) sperm in Freund's adjuvant either subcutaneously (s.c.), transcervically into the uterine lumen (i.u.), or with a combination of s.c. and i.u. immunization approaches. Control mice received DBA/2 lymphocytes, human erythrocytes or saline in adjuvant using the same immunization protocols. Immunization with sperm or control cells in adjuvant exclusively by s.c. or i.u. approaches did not affect subsequent fertility, although sperm-injected mice from both protocols had high titers of circulating antisperm antibodies. In contrast, mice that were immunized with sperm in adjuvant by a combination of s.c. and i.u. injections demonstrated significant reductions in fertilization rate and number of viable fetuses and an increased rate of fetal resorption when compared with non-immunized and control immunized mice. Mice receiving sperm by the s.c./i.u. protocol had high titers of antisperm antibodies and a marked infiltration of T lymphocytes and macrophages into the uterine endometrium. To determine whether cellular immune mechanisms contributed to the infertility effect, T lymphocytes from spleens and pelvic lymph nodes of s.c./i.u. sperm-immunized mice and non-immunized mice were passively transferred to naive syngeneic female recipients which were subsequently mated. The total number of fetuses on day 15 of pregnancy was significantly reduced in mice receiving T-lymphocytes from sperm-immunized mice and a significant increase in fetal resorption sites was also observed. These mice did not have detectable titers of circulating antisperm antibodies, but had a significant infiltration of CD4+ T lymphocytes and macrophages in the uterine epithelium and endometrium. These data indicate that intrauterine antisperm cell mediated immunity can be induced in mice by a combination of systemic and intrauterine immunizations and provide evidence for the existence of reproductive tract mucosal antisperm cellular immune responses that adversely affect fertility and pregnancy. PMID- 1453393 TI - Alloimmune neonatal neutropenia is a potential side effect of immunization with leukocytes in women with recurrent spontaneous abortions. AB - Alloimmunization of a mother against granulocytes causing alloimmune neonatal neutropenia (ANN) in her newborn was found likely to be attributed to previous intradermal injections of paternal lymphocytes. Immunotherapy with leukocytes which was performed for recurrent spontaneous abortions hence provides the possibility of granulocyte alloimmunization and increases the risk of the occurrence of ANN. PMID- 1453394 TI - Laparoscopic uterine suspension as an adjunctive procedure at the time of laser laparoscopy for the treatment of endometriosis. AB - Uterine suspension has been advocated as an adjunctive procedure at the time of conservative surgery for endometriosis but has seldom been used at the time of CO2 laser laparoscopic treatment of endometriosis. In this study of 225 patients treated for cul-de-sac endometriosis by CO2 laser laparoscopy between 1984 and 1989 uterine suspension was performed as an adjunctive procedure at the time of laparoscopy. The result was a cumulative pregnancy rate of 80.0%. Life-table analysis was performed, and monthly fecundity rates were calculated as 15.58%, 6.29%, 17.86% and 7.89% for Revised American Fertility Society (RAFS) endometriosis stages I to IV respectively. CO2 laser laparoscopy and laparoscopic uterine suspension alleviated preoperative pelvic pain complaints in 94% of the patients. Monthly fecundity rates for RAFS stage I endometriosis, which exceeded previously reported rates following expectant management, medical management and conservative surgery, were attributed to laparoscopic uterine suspension, which had not been previously reported as an adjunct to CO2 laser laparoscopy. PMID- 1453395 TI - Effect of thrombin-induced hemostasis on the efficacy of an absorbable adhesion barrier. AB - Serosal injury, bleeding and fibrin deposition are major factors in the development of surgical adhesions; meticulous hemostasis is desirable but not always achievable. The effects of thrombin on adhesion formation and the performance of Interceed Barrier were tested in separate series using a standard model and two levels of bleeding: an "oozing" model in which rabbit uterine horns were scraped to produce uncontrolled punctate bleeding and a "bleeding" model, in which four small blood vessels nicked on the ligament to each horn produced heavier bleeding. Substantial clots in the bleeding model were not removed. Adhesions, assessed after two weeks, were not worsened by the use of thrombin to control bleeding. While Interceed Barrier alone did not reduce adhesions at sites of bleeding, achieving hemostasis with thrombin and then applying Interceed Barrier significantly reduced adhesions. The effect was not achieved by applying thrombin to previously blood-soaked Interceed Barrier. The efficacy of Interceed Barrier applied after achieving hemostasis was further improved by moistening it with heparin. Achieving hemostasis at a bleeding site with thrombin facilitates the efficacy of Interceed Barrier. PMID- 1453396 TI - Clinical and histologic classification of endometriomas. Implications for a mechanism of pathogenesis. AB - One hundred eighty-seven consecutive patients with persistent ovarian cysts and endometriosis underwent laparoscopic evaluation and ovarian cystectomy. All patients had been followed for a minimum of 6 weeks prior to surgery. The cysts were identified initially to be endometriomas based on their gross appearance and the presence of endometriosis at other pelvic sites. Presumed endometriomas were classified into three types based on size, cyst contents, ease of removal of the capsule, adhesions of the cyst to other structures and location of superficial endometrial implants relative to the cyst wall. After clinical laparoscopic classification, the cysts were evaluated histologically without knowledge of the clinical assessment. Histologically small (< 2 cm), superficial ovarian cysts were always endometriomas, and the cyst wall was very difficult to remove (type I). Large cysts with easily removed walls were usually luteal cysts (type II). Large cysts with walls adherent in multiple areas adjacent to superficial endometriosis were generally endometriomas but some also had histologic characteristics of functional (luteal or follicular) cysts (types IIIa and IIIb). These findings led to the conclusion that superficial ovarian endometriosis is similar to endometriosis in extra-ovarian sites in that the formation of superficial cysts is limited in size by fibrosis and scarring. In contrast, large endometriomas may develop as a result of secondary involvement of functional ovarian cysts by the endometriotic process. PMID- 1453397 TI - Laparoscopic supracervical hysterectomy using a single-umbilical puncture (mini laparoscopy). AB - Laparoscopic supracervical hysterectomy with bilateral salpingo-oophorectomy utilizing the single-puncture technique (mini-laparoscopy) is presented here for the first time. The surgical outcome of four patients in whom this minimally invasive approach was employed demonstrates the effectiveness of the single puncture technique as an alternative to the currently used multiple-puncture method for hysterectomy. Laparoscopic supracervical hysterectomy with removal of the uterus and adnexa through the umbilical puncture site is an effective alternative for patients with a healthy cervix, no associated genital prolapse and moderate uterine enlargement. Advantages of this new modality include reduced blood loss and operating time, and the decreased possibility of surgical injury to the ureters, bladder and bowels. The risk of development of malignancy in the retained stump is almost eliminated by the laparoscopic removal of the upper endocervical canal and cauterization of the lower endocervical canal and exocervix. PMID- 1453398 TI - Determining the time of the urinary luteinizing hormone surge. Does it facilitate the interpretation of endometrial biopsy results? AB - Recent data suggest that endometrial maturation correlates highly with the postovulatory day as determined by ultrasound or identification of the urinary luteinizing hormone (LH) surge. A study was performed to determine the level of correlation between two methods of endometrial biopsy (EB) interpretation. Method 1 correlated histology with the onset of the next menstrual period; method 2 correlated it with the postovulatory day relative to the LH surge. Forty EBs were analyzed. Both methods agreed that 20/40 EBs were in phase and 6/40 EBs were out of phase (greater than a two-day lag between histologic endometrial maturation and chronologic dating). Of the remaining 14 EBs, 8 were in phase by method 1 and out of phase by method 2, and 6 were out of phase by method 1 and in phase by method 2. Thus, 35% of EBs were considered in phase by one method and out of phase by the alternative method. This implies that 35% of management decisions regarding whether to repeat an EB or treat an out-of-phase EB may be influenced by the method of interpreting EBs. PMID- 1453399 TI - Decreased amniotic fluid index in term pregnancy. Clinical significance. AB - In a study of 331 term pregnancies a four-quadrant technique was used to obtain amniotic fluid index measurements, and the results were compared with the current widely used single-pocket measurement. In contrast to the "2-cm rule," the amniotic fluid index measurements consistently demonstrated higher sensitivity in predicting poor fetal outcome with no decrease in specificity. It was noted that pregnancies with an index of < or = 8 cm showed higher incidences of meconium staining, cesarean delivery for fetal distress, abnormal fetal heart rate monitoring and Apgar scores of < or = 7 or less at one minute. PMID- 1453400 TI - Fetal weight-cerebellar diameter discordance as an indicator of asymmetrical fetal growth impairment. AB - In this study on the effect of fetal growth impairment < or = 25th percentile on the transverse cerebellar diameter and its relationship with other fetal biometric parameters, the sample comprised 50 women with singleton pregnancies referred for ultrasound evaluation because of clinically suspected intrauterine growth retardation. The cerebellar diameter of asymmetrically growth-impaired fetuses remained within the normal range although it was found to be reduced when compared with that of normal fetuses (4.4 +/- 0.9 versus 4.8 +/- 0.7, P < .05). Although other biometric parameters (biparietal diameter, femur length and abdominal and head circumferences) were also reduced in growth-impaired fetuses, the ratios of these biometric parameters to cerebellar diameter were similar to those of unaffected fetuses. Fetal weight was affected to a greater extent than the cerebellar diameter, leading to discordance between the two parameters. This discordance identified almost all asymmetrically growth-impaired fetuses with a sensitivity of 95.6% and specificity of 96.3%. In contrast, the ratio of head circumference to abdominal circumference remained normal in more than half of the fetuses. Fetal weight-to-cerebellar diameter discordance is a very sensitive and specific indicator of asymmetrical fetal growth impairment. PMID- 1453401 TI - Inflammatory cell infiltrate in the cervix as a predictor of residual cervical intraepithelial neoplasia after conization. AB - From January 1985 to January 1991, 112 patients underwent conization of the cervix for dysplasia. Twenty-one had incomplete resection, with cervical intraepithelial neoplasia (CIN) extending to the endocervical margins of resection. Only 10 had persistent CIN in follow-up. A decrease in the inflammatory cell infiltrate in the cervical stroma of the conization specimen was associated with persistent disease. A simple technique for quantitating this inflammatory cell infiltrate was used. Smoking was associated with a suppression of this local immune response in the cervix. PMID- 1453402 TI - Nonstress test assessment of twins. AB - Twin pregnancies have higher perinatal morbidity and mortality rates than singleton pregnancies. Researchers have demonstrated that one major benefit of prenatal care in the twin gestation is reduced fetal death rate. This study to determine the relationship of nonstress tests (NSTs) to pregnancy outcome in twin gestations comprised 665 women who delivered at Los Angeles County-University of Southern California Women's Hospital from January 1985 to January 1989. These patients, all of whom had prenatal care (PNC), were subdivided into two groups: (1) PNC and NSTs and (2) PNC and no NSTs. The groups did not differ statistically with regard to gravidity, parity and abortions. NSTs were selectively done on twin gestations complicated by discordancy or other fetal/maternal complications. Ten pregnancies were complicated by fetal demise of one or both twins in patients who received prenatal care without NSTs. Among the NST group there was one fetal demise. Although the NST group had fewer fetal deaths, the reduction was not statistically significant (P = .062). Infant birth weight was identified as a confounder because the NST group had a statistically higher mean birth weight. Definitive proof of the ability of NSTs to reduce the fetal death rate in twin gestations complicated by discordancy or other pregnancy complications awaits a large, prospective, randomized trial. PMID- 1453403 TI - Epidermal thickness measurements in vaginal intraepithelial neoplasia. A basis for optimal CO2 laser vaporization. AB - The current management of vaginal intraepithelial neoplasia (VAIN) often involves the use of laser vaporization. A study was performed to measure the epithelial thickness in both premenopausal and postmenopausal women with various grades of VAIN to determine the optimum depth of tissue destruction if laser vaporization is used for therapy. Hematoxylin and eosin-stained tissue sections were examined with light microscopy and measurements made with a calibrated micrometer. Sixty three biopsies from 56 patients were studied. Patients' ages ranged from 22 to 84 years, with a mean of 56. Thirty-six had a prior history of cervical neoplasia. Thirty-nine patients (70%) had VAIN III, 10 had VAIN II, and the remaining 7 patients had VAIN I lesions. The involved epithelium varied from 0.10 to 1.4 mm in thickness, with a mean of 0.46. Noninvolved vaginal epithelium varied in thickness from 0.10 to 0.70 mm, with a mean of 0.28. Koilocytosis was noted in only 9 of the 63 biopsy specimens. In comparing the thickness of involved epithelium in a given patient to that of an adjacent area of normal-appearing epithelium, the epithelium containing VAIN tended to be thicker. The recommended depth of epithelial destruction with laser vaporization in the literature varies widely and appears to have largely an empiric basis. Our study attempted to provide a scientific basis for laser destruction of these lesions. The results obtained indicate that epithelial destruction to a depth of 1.5 mm, including the zone of thermal necrosis, should be sufficient to destroy epithelium containing VAIN without damage to surrounding structures. PMID- 1453404 TI - Extraovular and intraovular uterine contraction monitoring. A comparison. AB - We tested a new method of monitoring intrauterine contraction pressure. The pressure transducer is simply inserted between the fetal membranes and uterus after checking placental placement with ultrasonography. To evaluate this method, a prospective, randomized study was done to compare intraovular versus extraovular intrauterine contraction monitoring in patients undergoing serial labor induction with oxytocin. Study parameters were length of labor, cesarean section rate, Apgar scores and febrile morbidity rate. Two groups of 32 patients each underwent oxytocin induction for postdatism, diabetes or hypertensive disorders of pregnancy. Our results show that extraovular intrauterine contraction monitoring resulted in a better outcome with respect to all the parameters evaluated. Specifically, it had a shorter induction interval, lower cesarean section rate, lower rate of maternal febrile morbidity and comparable neonatal complications. The technique was safe and easy to learn and apply. PMID- 1453405 TI - Prophylactic intrapartum amnioinfusion for patients with oligohydramnios. A prospective randomized study. AB - This prospective study evaluated whether prophylactic saline amnioinfusion among patients with amniotic fluid index (AFI) < or = 5.0 cm decreases the incidence of adverse fetal outcomes. Randomization of 53 patients with decreased AFI at term, resulted in 21 patients' receiving prophylactic saline amnioinfusion early in labor, prior to development of an abnormal fetal heart rate tracing. For the treatment group the mean AFI on admission was 3.0 cm, and the postamnioinfusion AFI was 8.9 cm. For 32 comparison (noninfusion) patients, the mean AFI was 2.9 cm; the group consisted of 17 patients randomized to receive no amnioinfusion (control group) and 15 patients who refused to participate in the study. There was no statistically significant difference between the amnioinfused and nonamnioinfused patients with regard to age, parity, gestational age, AFI at admission or duration of first or second stage of labor. Amnioinfusion resulted in no statistically significant reduction in the incidence of recurrent variable decelerations/bradycardia (26.3% vs. 46.6%), intrapartum resuscitation with terbutaline (5.2% vs. 10.0%), cesarean section for fetal distress (9.5% vs. 9.3%), fetal-acidosis (10.5% vs. 12.0%) or Apgar scores < 7 at five minutes (5.2% vs. 0%) in patients with oligohydramnios. PMID- 1453406 TI - AIDS (HIV) risk assessment in an inner-city women's clinic. AB - Risk assessment and antibody testing are potential modalities through which interventions to reduce heterosexual and perinatal transmission of human immunodeficiency virus (HIV) can occur. More than 98% of women attending inner city adult gynecology, adult contraception and teen family planning clinics successfully completed self-administered HIV (AIDS) risk assessment questionnaires and received individual counseling, risk-reduction education and referral for antibody testing. Fourteen percent of the women (671/4,802) reported at least one HIV risk factor. Multiple sexual partners and intravenous drug use were the most commonly reported HIV risk factors in this population. PMID- 1453407 TI - Incidence of salmonellosis in local hens' eggs. AB - Evidence indicates that outbreaks of salmonellosis may be due to infected eggs. This prompted a study on the incidence of salmonella in eggs. This study was done during summer 1991 and 900 eggs were examined in all. None of the eggs examined were found to be infected with salmonella. However, the result obtained should be treated with care and analysed with a critical eye. The result obtained does not imply that local flocks are not infected by salmonella. PMID- 1453408 TI - Mefenamic acid in prevention of premature labour. AB - Women at risk of premature delivery were divided randomly into 2 groups of 80 each. Mefenamic acid 500mg 3 times a day or a placebo was given in a double blind fashion. Preterm delivery occurred in 15% of the treated group and 40% of the control group (p < 0.005). The mean birth weight in the test group was higher as compared to the controls. There were no cases of foetal malformations in either of the groups. The results support the use of Mefenamic acid in preventing premature labour. PMID- 1453409 TI - Dietary habits of technical and vocational students in Riyadh, Saudi Arabia--I. Meal skipping. AB - 452 male technical and vocational students aged 16-25 years old were surveyed for their dietary habits at Riyadh, Saudi Arabia. The data presented here cover the habit of meal skipping. Results showed that dinner was skipped by 28%, breakfast by 20% and lunch was skipped by 15%. Differences are discussed according to age cohorts and accommodation status subgroups. PMID- 1453410 TI - Environmental health and the South African community. AB - The success of an environmental impact assessment programme will depend on the perceptions of a community. There are differences in the opinion of the population groups of South Africa concerning the perceived environmental threats to health. PMID- 1453411 TI - Lying in children. AB - Lying is a common problem in children. The causes of lying are numerous. With proper management including good parental role models, minimising or preventing contributing factors, and appropriate discipline, most children outgrow the tendency to lie. PMID- 1453412 TI - Older adult learners: a guide for food safety trainers. PMID- 1453413 TI - Physical exercise/sports and biopsychosocial well-being. PMID- 1453414 TI - A consumer-led approach to designing buildings for elderly nursing care. PMID- 1453415 TI - Hypnotism--curse or cure for smokers? PMID- 1453416 TI - The Children Act--partnership with families. PMID- 1453417 TI - Multidisciplinary case conference; fulcrum, fudge, or fix? PMID- 1453418 TI - Health professions in 1992: the European challenge--the challenge for nursing. PMID- 1453420 TI - Presidential politics and health care issues. PMID- 1453419 TI - Single market or single Europe: the challenge for European social work. PMID- 1453421 TI - Setting a good example. PMID- 1453422 TI - Instability versus predictability: the molecular diagnosis of myotonic dystrophy. PMID- 1453423 TI - Comparison of the myotonic dystrophy associated CTG repeat in European and Japanese populations. AB - Gene amplification using polymerase chain reaction (PCR) was carried out on DNA samples from a total of 92 normal subjects and 52 subjects with myotonic dystrophy (DM) from European and Japanese populations, to determine the copy number of the CTG repeat associated with DM for each group. In the two populations, the number of repeats on normal chromosomes only were compared, as CTG copy number on DM chromosomes was difficult to determine by PCR alone. In this study, normal chromosomes were found which had as many as 35 copies of the repeat, which is larger than the normal range reported previously but still does not overlap with the repeat number associated with DM pathology, which is at least 50 copies. Using data from normal chromosomes from unrelated subjects, the frequencies of five, 11, and 13 copies of the CTG repeat were found to be significantly different between the two populations, with five and 11 copies more commonly seen in the European population and 13 copies in the Japanese population. This difference may be the result of natural divergence of the normal chromosomes between the population groups. PMID- 1453424 TI - Minimal expression of myotonic dystrophy: a clinical and molecular analysis. AB - A clinical and molecular study is reported of 83 patients considered to be minimally affected with myotonic dystrophy (DM). These had been identified in three ways: 60 subjects were identified on clinical grounds and were divided into those with and those without neuromuscular involvement (groups I and II); nine subjects were at high risk of carrying the DM gene but had a normal phenotype (group III); and 14 were parents of definitely affected patients where neither parent showed clinical abnormalities (group IV). PCR analysis of the CTG repeat in the DM gene showed a range of 70 to 230 repeats for the younger at risk patients in group III, while the asymptomatic gene carriers in group IV had 53 to 60 repeats. The sensitivity of diagnosis by EMG was found to be 39%. For ophthalmic signs this was 97.5%. This suggests that assignment on the basis of minimal clinical features carries a significant error. Molecular analysis, in conjunction with established clinical investigations, should prove valuable in the identification and exclusion of minimal myotonic dystrophy. PMID- 1453425 TI - The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy. AB - The gene for myotonic dystrophy (DM) has recently been isolated and amplification of an unstable CTG trinucleotide repeat, located within the DM gene, has been identified in virtually all patients studied to date. A high proportion of DM families who are studied show a progressively earlier age of onset with succeeding generations and, in the few pedigrees reported so far, an increasing degree of amplification of the CTG repeat has been noted to parallel this trend. It has been implicit in several of the original reports on the nature of the changes in the DM gene that knowledge of CTG amplification status at the DM locus of a person will provide useful information concerning prognosis. However, no studies of genotype-phenotype correlation have been reported and there are no specific data on which to base such counsel. In this paper we report the correlation between the degree of CTG amplification and age of onset in 109 DM gene carriers from 17 families. Included are parent-child and sib-sib comparisons which provide a framework in which to incorporate DNA diagnostic studies when counselling subjects and families at risk for DM. PMID- 1453426 TI - Presymptomatic diagnosis of myotonic dystrophy. AB - The discovery of an expanded (CTG)n repeat sequence in myotonic dystrophy (DM) has greatly improved our ability to detect DM gene carriers who have few or none of the classical signs of this disorder. We report here our experience with two such groups of gene carriers. We used a PCR based protocol that should be especially sensitive to small increases in CTG triplet number which might escape detection by conventional Southern blot analysis. Our analyses show that on 100 non-DM chromosomes the number of CTG triplets ranged from five to 37. We then studied 17 obligate gene carriers aged 55 years and over who showed no muscle weakness. All of the gene carriers in this group showed a relatively small increase in the number of CTG triplets (52 to 90 CTG triplets) with limited somatic mosaicism. We subsequently studied 11 subjects (aged 19 to 36 years) who had previously been identified as gene carriers by genetic linkage studies, but who lacked diagnostic signs. In this prospectively studied group, nine subjects showed an expanded allele, confirming the earlier prediction from linked genetic markers. The other two subjects had only two normal alleles and no expanded allele. Revision of the clinical data casts doubt on the original diagnosis of DM in their families. Preferential amplification of the normal non-expanded allele was noted in three asymptomatic gene carriers in this study (as well as in two of their clinically affected relatives). We caution that, at least in our hands, the DM mutation can be confidently excluded by this PCR based method only if both normal alleles have been identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453427 TI - Specific molecular prenatal diagnosis for the CTG mutation in myotonic dystrophy. AB - The results of DNA analysis for the specific mutation of myotonic dystrophy are reported in eight pregnancies (two studied retrospectively) in six families. Four results were normal; in the other four, large DNA expansions were found, comparable to the range seen in severely affected children with congenital onset of the disorder. The results agreed with those obtained by linked DNA markers in the six cases where they were available. We conclude that specific molecular prenatal diagnosis of myotonic dystrophy is feasible, and that an abnormal result may also give a guide to possible severity, though this should be interpreted with caution until greater experience is available. PMID- 1453428 TI - Expansion of the myotonic dystrophy gene in Italian and Spanish patients. AB - Myotonic dystrophy results from expansion of a (CTG)n repeat at the 3' untranslated region of the myotonin-protein kinase gene. We show here the genomic analysis of 322 symptomatic patients with the cDNA-25 probe detecting disease specific EcoRI restriction fragments. The expansion was found in the majority of Italian and Spanish patients (92%). The implications of these results for the detection of symptomatic patients in southern Europe are discussed. PMID- 1453429 TI - Intestinal pseudo-obstruction in myotonic dystrophy. AB - We describe four myotonic dystrophy (DM) patients who developed recurrent intestinal pseudo-obstruction. Some episodes were associated with gastroenteritis, while abdominal crowding may have occurred in one case during the third trimester of pregnancy. In most instances, however, no apparent cause could be identified. Intestinal pseudo-obstruction may occur at any stage of DM. In one of our cases intestinal pseudo-obstruction preceded significant muscle weakness by 15 years. Intestinal pseudo-obstruction is usually treated effectively with conservative measures. These include restriction of oral intake, intravenous fluids, and multiple enemas or colonoscopy. Improved intestinal function was noted in one case treated with the prokinetic agent cisapride. A partial sigmoid resection was performed in three cases with dolichomegacolon. No abnormalities were reported on histological examination. Since intestinal pseudo obstruction is a rare complication of DM, it is of interest that two of our cases are sibs. Review of published reports showed several reports of familial occurrence of specific complications. These include cardiac conduction disturbances, focal myocarditis, mitral valve prolapse, pilomatrixomas, polyneuropathy, normal pressure hydrocephalus, and dilatation of the urinary tract. Myotonic dystrophy may show a tendency to familial clustering of organ specific involvement. PMID- 1453430 TI - Inheritance of the fragile X syndrome: size of the fragile X premutation is a major determinant of the transition to full mutation. AB - The fragile X mental retardation syndrome is caused by unstable expansion of a CGG repeat. Two main types of mutation have been categorised. Clinical expression is associated with the presence of the full mutation, while subjects who carry only a premutation do not have mental retardation. Premutations have a high risk of transition to full mutation when transmitted by a female. We have used direct detection of the mutations to characterise large families who illustrate the wide variation in penetrance which has been observed in different sibships (a feature often called the Sherman paradox). A family originally found to show tight genetic linkage between the factor 9 gene and the fragile X locus was reanalysed, confirming the original genotype assignments and the observed linkage. The size of premutations was measured by Southern blotting and by using a PCR based test in 102 carrier mothers and this was correlated with the type of mutation found in their offspring. The risk of transition to full mutation was found to be very low for premutations with a size increase (delta) of about 100 bp, increasing up to 100% when the size of premutation was larger than about 200 bp, even after taking into account (at least partially) ascertainment bias. These results confirm and extend those reported by Fu et al (1991) and Yu et al (1992) and explain the Sherman paradox.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453431 TI - Frequent small amplifications in the FMR-1 gene in fra(X) families: limits to the diagnosis of 'premutations'. AB - In five of 40 fra(X) families reinvestigated using the new intragenic probe StB12.3, small amplifications of the DNA fragment appeared unexpectedly in addition to the mutations found in the probands. This suggests that enlargements of the FMR-1 gene detectable by Southern blotting using this probe must be present at an appreciable frequency in the general population. A proportion of these may be classifiable as 'premutations', or precursors of the much amplified, hypermethylated, and somatically unstable fragment associated with the fragile X syndrome, while others will merely represent stable polymorphisms in fragment length. Hence, accurate diagnosis of some fra(X) carriers will depend upon a more precise measurement of insert size than is currently provided by the newly available molecular probes. PMID- 1453433 TI - High frequency of the Lebanese allele of the LDLr gene among Brazilian patients with familial hypercholesterolaemia. AB - We analysed the LDL receptor (LDLr) gene in 18 Brazilian patients with familial hypercholesterolaemia (FH) from 10 unrelated families. The combination of a direct search for the Lebanese allele of the LDLr gene by a PCR method and Southern blotting using cDNA probes allowed the identification of the gene defect in six out of 10 families. The Lebanese allele was found in five families and in one family the disease was caused by a 4 kb deletion in the 3' half of the LDLr gene. The results indicate an important contribution of the Lebanese allele to the prevalence of FH in the Brazilian population and suggest that it may also be the most common cause of FH in other mixed populations outside the Middle East. PMID- 1453432 TI - Duplication within chromosome 17p11.2 in 12 families of French ancestry with Charcot-Marie-Tooth disease type 1a. The French CMT Research Group. AB - Hereditary motor and sensory neuropathy type I (HMSN I), also designated Charcot Marie-Tooth disease type 1 (CMT1), is a peripheral neuropathy frequently inherited as an autosomal dominant trait, characterised by progressive distal muscular atrophy and sensory loss with markedly decreased nerve conduction velocity. A duplication within chromosome 17p11.2, cosegregating with the disease, has recently been reported in several CMT1a families. In order to estimate the frequency of this anomaly and determine the location of a duplication in this region, 12 CMT1 families were analysed with polymorphic DNA markers located within 17p11.2-12. Duplications were found in all families including loci D17S61 (EW401), D17S122 (VAW409R3a and RM11-GT), and D17S125 (VAW412R3). The duplications were completely linked and associated with the disease (lod score of 20.77 at zero recombination). Screening for the RM11-GT microsatellite showed that most of the duplicated haplotypes were heterozygous, supporting the hypothesis that the duplication resulted from an unequal crossing over. There was no significant haplotype association within the duplicated region suggesting that the duplication resulted de novo as an independent event in each family. In one family, recombination within the duplicated region was observed, indicating that genetic instability in 17p11.2 might be related to a high recombination rate. Since most cases of CMT1a seem to result from this segmental trisomy, it can be used as a basis for DNA diagnosis of the disease. PMID- 1453434 TI - Clinical reinvestigation and linkage analysis in the family with Episkopi blindness (Norrie disease). AB - We present the results of a clinical and genetic reinvestigation of the Cypriot family affected by an X chromosomally inherited eye disease originally published by Taylor et al, who coined the term Episkopi blindness. The pedigree was extended to 160 members, including 16 affected males out of 48 males at risk for the disease, most of whom were seen by one of us (PA). Affected males are blind with no associated symptoms and apparently are not mentally retarded. Thirty-nine family members agreed to blood sampling for genetic investigations. RFLP analysis was performed using probes from the region known to be deleted in some Norrie patients and polymorphic markers (DXS77, DXS7, MAOA, DXS255) from the proximal short arm of the X chromosome. There was no deletion for any of the probes in the affected males. Linkage analysis yielded positive lod scores for all informative markers (Z (DXS255, theta = 0) = 6.54, Z (MAOA, theta = 0) = 2.23, Z (DXS7, theta = 0) = 2.13). Thus, the conclusion that Episkopi blindness and Norrie disease (NDP, MIM *310600) are the same entity based on clinical evidence is now reinforced by gene mapping. PMID- 1453435 TI - Factors affecting the uptake of prenatal diagnosis for sickle cell disease. AB - Between 1979 and 1990, 170 couples at risk of having children with sickle cell disease, resident in the UK and with a continuing pregnancy, were referred for counselling at the University College Hospital Perinatal Centre. Approximately 50% of the couples, including those where one partner actually had sickle cell disease, requested prenatal diagnosis. This was requested in 82% of pregnancies when the mother was seen in the first trimester of pregnancy and in 49% when she was seen in the second trimester. More than 90% of referred couples who already had an affected child requested prenatal diagnosis. The type of sickle cell disease involved and ethnic group also influenced choice. These results show the importance of detecting and counselling couples at risk before pregnancy whenever possible. PMID- 1453436 TI - Polyglandular autoimmune syndrome type I among Iranian Jews. AB - Polyglandular autoimmune syndrome (PAS) has been well characterised and the accepted criteria for diagnosis are the presence of at least two of the three major components: hypoparathyroidism (HPT), candidiasis, and adrenal insufficiency (AI). HPT may, however, be the only manifestation of the syndrome. Iranian Jews, having a high rate of consanguinity, appear to be a community in which PAS type I is frequent. We report on 19 families of patients with HPT from the Iranian Jewish community assuming that they are in fact affected with PAS type I. In the 19 families, 23 patients were affected, including 11 males and 12 females. All the patients but one had HPT (96%), and most were diagnosed by the age of 20 years (91%). AI was diagnosed in five of our patients; in all cases but one it appeared after HPT. Mild oral candidiasis was present in four patients and six of the patients (three males and three females) had hypogonadism. Other features of the syndrome found in some of our patients were pernicious anaemia, hypothyroidism, and alopecia. The disease is autosomal recessive and the calculated prevalence among the Iranian Jews is 1:6500 to 1:9000. The disease is also found with a very high incidence among Finns. A comparison of the symptoms between the two groups showed clinical differences including the relative rarity of candidiasis and absence of keratopathy among the Iranian Jews. PMID- 1453437 TI - Orofaciodigital syndrome type I in a girl with unilateral tibial pseudarthrosis. AB - The orofaciodigital syndromes are a group of possibly seven different malformation syndromes including oral, facial, and digital malformations. Type I has X linked dominant inheritance whereas the other types show autosomal recessive inheritance. An exact diagnosis is therefore important for genetic counselling. We here report a girl with orofaciodigital syndrome type I. She had cystic kidney disease at the age of 8 months which has not previously been reported in an infant with orofaciodigital syndrome. In addition she had unilateral tibial pseudarthrosis which has only rarely been reported in the orofaciodigital syndromes and in type II only. PMID- 1453438 TI - Lethal skeletal dysplasia owing to double heterozygosity for achondroplasia and spondyloepiphyseal dysplasia congenita. AB - A male infant with lethal short limbed dwarfism is described. His father had spondyloepiphyseal dysplasia congenita and his mother had achondroplasia. It is believed that the infant inherited both of these disorders and that their combined effects resulted in early death owing primarily to severe pulmonary hypoplasia. PMID- 1453439 TI - An atypical form of mucolipidosis III. AB - We report two sibs showing a very mild form of mucolipidosis III with no clinical signs but isolated involvement of the hip and very mild abnormalities of the spine. This indicates that a storage disease, in particular mucolipidosis III, should be considered in any case of isolated bilateral hip dysplasia. The differences from other reported atypical variants of mucolipidosis III are discussed. PMID- 1453440 TI - De novo inverted duplication of chromosome 7q. PMID- 1453441 TI - Numerous group I introns with variable distributions in the ribosomal DNA of a lichen fungus. AB - The length of the small subunit ribosomal DNA (SSU rDNA) differs significantly among individuals from natural populations of the ascomycetous lichen complex Cladonia chlorophaea. The sequence of the 3' region of the SSU rDNA from two individuals, chosen to represent the shortest and longest sequences, revealed multiple insertions within a region that otherwise aligned with a 520-nucleotide sequence of the SSU rDNA in Saccharomyces cerevisiae. The high degree of variability in SSU rDNA size can be accounted for by different numbers of insertions; one individual had two group I introns and the second had five introns, two of which were clearly related to introns at identical positions in the other individual. Yet, introns in different positions, whether within an individual or between individuals, were not similar in sequence. The distribution of introns at three of the positions is consistent with either intron loss or acquisition, and clearly indicates the dynamic variability in this region of the nuclear genome. All seven insertions, which ranged in size from 210 to 228 nucleotides, had the conserved sequence and secondary structural elements of group I introns. The variation in distribution and sequence of group I introns within a short highly conserved region of rDNA presents a unique opportunity for examining the molecular evolution and mobility of group I introns within a systematics framework. PMID- 1453442 TI - An accurate method for determining the helical repeat of DNA in solution reveals differences to the crystal structures of two B-DNA decamers. AB - Many DNA sequences have been studied by X-ray crystallography with the goal of deciphering a sequence-structure code. We have determined the helical repeats of two B-type DNA decamers in solution employing an electrophoretic method based on phasing of bent segments. The decamers contain recognition sites for the dcm methyltransferase and for the restriction nuclease NarI with a mutational hotspot. Their helical repeats are 10.59(+/- 0.05) bp and 10.52(+/- 0.03) bp, respectively, whereas crystallographic analysis yielded 10.0 bp in the solid state. This difference is greater than that for the transition between B- and A type DNA in solution. Thus, reliable information about the polymorphism of DNA in solution must be based on both X-ray and solution data. We describe a generally applicable approach to accurately determine helical repeats of small DNA duplexes in solution. PMID- 1453443 TI - Chromatin reconstitution on small DNA rings. V. DNA thermal flexibility of single nucleosomes. AB - The thermal flexibility of DNA minicircles reconstituted with single nucleosomes was measured relative to the naked minicircles. The measurement used a new method based on the electrophoretic properties of these molecules, whose mobility strongly depended on the DNA writhe, either of the whole minicircle, when naked, or of the extranucleosomal loop, when reconstituted. The experiment was as follows. The DNA length was first increased by one base-pair (bp), and the correlative shift in mobility resulting from the altered DNA writhe was recorded. Second, the gel temperature was increased so that the former mobility was restored. Under these conditions, the untwisting of the thermally flexible DNA due to the temperature shift exactly compensates for the increase in the DNA mean twist number resulting from the one bp addition. The relative thermal flexibility was then calculated as the ratio between the increases in temperature measured for the naked and the reconstituted DNAs, respectively. The figure, 0.69 (+/- 0.07), was used to derive the length of DNA in interaction with the histones, 109 (+/- 25) bp. Such length was in good agreement with the mean value of 115 bp we have previously obtained from the distribution of the angles between DNAs at the entrance and exit of similar nucleosomes measured from high resolution electron microscopy. This consistency further reinforces our previous conclusion that minicircle-reconstituted nucleosomes, with 1.3(109/83) to 1.4(115/83) turns of superhelical DNA, show no crossing of entering and exiting DNAs when the loop is in its most probable configuration, and therefore, that these nucleosomes behave topologically as "single-turn" particles. The present data are also within the range of values, 50 to 100 bp of thermally rigid DNA per nucleosome, obtained by others for yeast plasmid chromatin, suggesting that the "single-turn" particle notion may be extended to this particular case of naturally-occurring H1-free chromatin. However, these data are quite different from the 230 bp figure derived from thermal measurements of reconstituted H1-free minichromosomes. It is proposed that nucleosome interactions occurring in this chromatin, but not in yeast chromatin, may be partly responsible for the discrepancy. PMID- 1453444 TI - A peptide model for proline isomerism in the unfolded state of staphylococcal nuclease. AB - Nuclear magnetic resonance spectroscopy has been used to investigate a synthetic peptide (YVYKPNNTHE) corresponding to residues 113 to 122 of staphylococcal nuclease. In the major folded state of the protein this region forms a type VIa beta-turn containing a cis Lys116-Pro117 peptide bond. There is, however, no evidence for any significant population of such a turn in the peptide in aqueous solution and the X-Pro bond is predominantly in the trans configuration. The peptide exhibits several well-resolved minor resonances due to the presence of a small fraction (4 +/- 2%) of the cis-proline isomer. The ratio of cis to trans isomer populations was found to be independent of temperature between 5 degrees C and 70 degrees C, indicating that delta H for the isomerism is close to zero. Using magnetization transfer techniques the rate of trans to cis interconversion was found to be 0.025(+/- 0.013) s-1 at 50 degrees C. The thermodynamics and kinetics of isomerism in the peptide are very similar to those estimated for the Lys116-Pro117 peptide bond in unfolded nuclease, suggesting that the cis-trans equilibrium in the unfolded protein is largely determined by the residues adjacent to Pro117 in the sequence. These results are consistent with previous suggestions that the cis-proline bond is stabilized late in the folding process and that the predominance of the cis form in folded nuclease is due to stabilizing interactions within the protein that give rise to a favorable enthalpy term. PMID- 1453445 TI - Molecular mechanism for ligand stabilization in the mollusc myoglobin possessing the distal Val residue. AB - Myoglobin extracted from the triturative stomach of Dolabella auricularia, a common mollusc found on the Japanese coast, possesses naturally occurring substitution at the distal E7 position (Val-E7) and its oxygen affinity is only slightly lower than those of the common mammalian myoglobins possessing the usual His-E7. 1H nuclear magnetic resonance studies of Dolabella met-cyano myoglobin have revealed that a guanidino NH proton of Arg-E10 is hydrogen-bonded to the Fe bound CN-. The role of Arg-E10 as a hydrogen-bond donor for Fe-bound ligand in the present myoglobin appears to be responsible for its relatively high ligand affinity. PMID- 1453446 TI - Absence of the thermal transition in apo-alpha-lactalbumin in the molten globule state. A study by differential scanning microcalorimetry. AB - To estimate the energy level of the molten globule state, the heat capacity function of apo-alpha-lactalbumin in the molten globule state has been examined using a scanning microcalorimeter at neutral pH. The results showed that the enthalpy difference between the molten globule state and presumed unfolded state by heating was almost zero at neutral pH, demonstrating that the molten globule state does not exhibit any co-operative transition upon heating. This is in agreement with the results already reported at acid pH, but is apparently in conflict with that recently reported with some assumptions at neutral pH. PMID- 1453447 TI - Folding on the ribosome of Escherichia coli tryptophan synthase beta subunit nascent chains probed with a conformation-dependent monoclonal antibody. AB - Experimental analysis of protein folding during protein synthesis on the ribosome is rendered very difficult by the low concentration of nascent polypeptides and the heterogeneity of the translation mixture. In this study, an original approach is developed for analysing nascent polypeptide structures still carried by the ribosome. Folding on the ribosome of nascent chains of the beta subunit of Escherichia coli tryptophan synthase was investigated using a monoclonal antibody (mAb 19) recognizing a conformation-dependent antigenic determinant. Upon synthesis of beta subunits in an E. coli coupled transcription-translation system, it is shown that ribosome-bound nascent polypeptides can react with the monoclonal antibody provided their size is above 11.5 kDa, which is smaller than that of both the N-terminal proteolytic and crystallographic domains (29 and 21 kDa, respectively). The gene fragments coding only for the 11.5 kDa polypeptide, with and without stop codon at the end of the corresponding mRNAs, were constructed and expressed in a cell-free wheat germ translation system. It is shown that antibody 19 reacts with this polypeptide either bound to the ribosome or free in solution. That the 11.5 kDa polypeptide acquires a condensed structure is shown by gel filtration in native conditions and by urea gradient gel electrophoresis. Moreover, it is demonstrated that this condensed structure resembles that of native beta 2 in the vicinity of the epitope for antibody 19. Indeed, the affinity of antibody 19 for the 11.5 kDa fragment, either free or bound to the ribosome, was measured (6 x 10(8) M-1) and shown to be close to that for native beta 2. It is therefore proposed that the polypeptide chain may start to fold during its biosynthesis and that, even before the appearance of an entire domain, a folded intermediate is formed that already exhibits some local structural features of the native state and of an immunoreactive intermediate previously detected during the in vitro refolding of denatured complete beta chains. PMID- 1453448 TI - General mutagenesis/gene expression procedure for the construction of variant immunoglobulin domains in Escherichia coli. Production of the Bence-Jones protein REIv via fusion to beta-lactamase. AB - A novel mutagenesis/gene expression and protein purification scheme was established for ready construction and purification of variant immunoglobulin domains in Escherichia coli. This procedure, which has been applied to the production of the VK domain of the Bence-Jones protein REI and structural variants of it, rests on the synthesis of chimeric proteins with beta-lactamase as the amino-terminal fusion partner. The beta-lactamase not only guides the fusion protein to the periplasmic space, but also allows affinity chromatography on phenylboronate-Sepharose as an efficient and general purification procedure, independent of hypervariable loop structure. The REIv protein was released from the purified fusion protein by site-specific proteolytic cleavage. After a second passage through the same affinity column, up to 2 mg of pure REIv was obtained starting from one liter of bacterial liquid culture. A scheme of oligonucleotide directed mutagenesis was introduced for replacement of DNA stretches encoding hypervariable loops. It exploits a colony color genetic screen and can be applied to any DNA sequence replacement. Mutations can be constructed by simple co transformation with single-stranded template DNA and mutagenic oligonucleotide. PMID- 1453449 TI - Messenger RNA secondary structure and translational coupling in the Escherichia coli operon encoding translation initiation factor IF3 and the ribosomal proteins, L35 and L20. AB - The Escherichia coli infC-rpmI-rplT operon encodes translation initiation factor IF3 and the ribosomal proteins, L35 and L20, respectively. The expression of the last cistron (rplT) has been shown to be negatively regulated at a post transcriptional level by its own product, L20, which acts at an internal operator located within infC. The present work shows that L20 directly represses the expression of rpmI, and indirectly that of rplT, via translational coupling with rpmI. Deletions and an inversion of the coding region of rpmI, suggest an mRNA secondary structure forming between sequences within rpmI and the translation initiation site of rplT. To verify the existence of this structure, detailed analyses were performed using chemical and enzymatic probes. Also, mutants that uncoupled rplT expression from that of rpmI, were isolated. The mutations fall at positions that would base-pair in the secondary structure. Our model is that L20 binds to its operator within infC and represses the translation of rpmI. When the rpmI mRNA is not translated, it can base-pair with the ribosomal binding site of rplT, sequestering it, and abolishing rplT expression. If the rpmI mRNA is translated, i.e. covered by ribosomes, the inhibitory structure cannot form leaving the translation initiation site of rplT free for ribosomal binding and for full expression. Although translational coupling in ribosomal protein operons has been suspected to be due to the formation of secondary structures that sequester internal ribosomal binding sites, this is the first time that such a structure has been shown to exist. PMID- 1453450 TI - A factor with Sp1 DNA-binding specificity stimulates Xenopus U6 snRNA in vivo transcription by RNA polymerase III. AB - We have previously shown that transcription of the Xenopus U6 snRNA gene by RNA polymerase III is stimulated in injected Xenopus oocytes by an activator element termed the DSE, which contains an octamer sequence. Data presented here reveal that the DSE contains, in addition, a GC-rich sequence capable of binding Sp1. Both elements are required to obtain wild-type levels of U6 transcription in vivo. The Xenopus U6 DSE exhibits optimal activation properties only when positioned at its normal location upstream from the start site. The U6 Sp1 motif binds the mammalian Sp1 transcriptional activator independently of the Oct-1 protein in vitro. Those mutations that lead to a reduced transcription level in vivo abolish the binding of Sp1 in vitro. Thus, transcriptional stimulation through the Xenopus U6 Sp1 motif is likely to be mediated by a protein with DNA binding specificity identical to mammalian Sp1. These findings support the notion that RNA polymerase II and III transcription complexes share transactivators. PMID- 1453451 TI - In vitro analysis of mutant LexA proteins with an increased rate of specific cleavage. AB - Specific cleavage of LexA repressor plays a crucial role in the SOS response of Escherichia coli. In vivo, cleavage requires an activated form of RecA protein. However, previous work has shown that the mechanism of cleavage is unusual, in that the chemistry of cleavage is probably carried out by residues in the repressor, and not those in RecA; RecA appears to facilitate this reaction, acting as a coprotease. We recently described a new type of lexA mutation, a class termed lexA (IndS) and here called IndS, that confers an increased rate of in vivo cleavage. Here, we have characterized the in vitro cleavage of these IndS mutant proteins, and of several double mutant proteins containing an IndS mutation and one of several mutations, termed Ind-, that decrease the rate of cleavage. We found, first, that the autodigestion reaction for the IndS mutant proteins had a higher maximum rate and a lower apparent pKa than wild-type LexA. Second, the IndS mutations had little or no effect on the rate of RecA-mediated cleavage, measured at low protein concentrations, implying that the value of Kcat/Km was unaffected. Third, the rate of autodigestion for the double-mutant proteins, relative to wild-type, was about that rate predicted from the product of the effects of the two single mutations. Finally, by contrast, these proteins displayed the same rate of RecA-mediated cleavage as did the single Ind- mutant protein. We interpret these data to mean that the IndS mutations mimic to some extent the effect of RecA on cleavage, perhaps by favoring a conformational change in LexA. We present and analyze a model that embodies these conclusions. PMID- 1453452 TI - Early stages in RecA protein-catalyzed pairing. Analysis of coaggregate formation and non-homologous DNA contacts. AB - RecA protein will catalyze the in vitro pairing of homologous DNA molecules. To further explore the events involved in the search for homology, we have applied a nitrocellulose filter binding assay to follow pairing, and a sedimentation assay to follow the generation of aggregates (termed coaggregates) formed between RecA complexed single-stranded (ss) DNA and double stranded (ds) DNA. Electron microscopy (EM) was used to visualize the structures involved. RecA protein promoted the pairing of circular M13 ssDNA and linear M13mp7 dsDNA efficiently in the absence of coaggregates. Indeed, pairing of homologous ss- and dsDNAs involved coaggregate formation only if the dsDNA was circular. For DNAs containing only a few hundred base-pairs of homology, for example pUC7 dsDNA and M13mp7 ssDNA, pairing and joint formation was observed if the dsDNA was superhelical but not if it was topologically relaxed or linear with the homology internal to an end of the dsDNA. The effect of non-covalently attached heterologous dsDNA on the RecA-promoted joining of M13 ssDNA and linear M13mp7 dsDNA (with non-M13 sequences at both ends) was found to depend on the topology and concentration of the heterologous DNA. A tenfold excess of superhelical pBR322 DNA strongly inhibited pairing. However, addition of relaxed or linear pBR322 DNA to the pairing reaction had little effect. As seen by EM, superhelical pBR322 DNA inhibited joint formation by excluding the homologous dsDNA form the coaggregates. EM also revealed heterologous DNA interactions presumably involved in the search for homology. Here the use of EM has provided a direct visualization of the form and architecture of coaggregates revealing a dense interweaving of presynaptic filaments and dsDNA. PMID- 1453453 TI - Structure of the pericentric long arm region of the human Y chromosome. AB - We have analysed the sequence organization of the DNA in the pericentric region of the long arm of the human Y chromosome. The structures of one cosmid and three yeast artificial chromosome clones were determined. The region consists of a mosaic of the known 5, 48 and 68 base-pair tandemly repeated sequences and at least five novel repeated sequence families. A long range-map of approximately 3.5 x 10(6) base-pairs of genomic DNA was constructed that placed the clones between about 500 x 10(3) and 850 x 10(3) base-pairs from the long arm edge of the centromeric alphoid DNA array. PMID- 1453454 TI - DNA sequence analysis of 66 kb of the human MHC class II region encoding a cluster of genes for antigen processing. AB - The genomic sequence of a 66,109 bp long region within the human MHC has been determined by manual and automated DNA sequencing. From cDNA mapping and sequencing data it is known that this region contains a cluster of at least four genes that are believed to be involved in antigen processing. Here, we describe the genomic organization of these genes, which comprise two proteasome-related genes (LMP2 and LMP7), thought to be involved in the proteolytic degradation of cytoplasmic antigens and two ABC transporter genes (TAP1 and TAP2), thought to be involved in pumping of the degraded peptides across the endoplasmic reticulum membrane. Analysis of the sequence homology and the intron/exon structures of the corresponding genes suggests that one gene pair arose by duplication from the other. Comparison of the available sequence data from other organisms shows striking conservation (70 to 84%) of this gene cluster in human, mouse and rat. The presence of several potential interferon stimulated response elements (ISREs) is in agreement with the experimentally observed up-regulation of these genes with gamma-interferon. PMID- 1453455 TI - Nucleosome core binding region of chromosomal protein HMG-17 acts as an independent functional domain. AB - Chromosomal proteins HMG-14 and HMG-17 have a modular structure. Here we examine whether the putative nucleosome-binding domain in these proteins can function as an independent module. Mobility shift assays with recombinant HMG-17 indicate that synthetic molecules can be used to analyze the interaction of this protein with the nucleosome core. Peptides corresponding to various regions of the protein have been synthesized and their interaction with nucleosome cores analyzed by mobility shift, thermal denaturation and DNase I digestion. A 30 amino acid long peptide, corresponding to the putative nucleosome-binding domain of HMG-17, specifically shifts the mobility of cores as compared to free DNA, elevates the tm of both the premelt and main melt of the cores and protects from DNase I digestion the same nucleosomal DNA sites as the intact protein. The binding of both the peptide and the intact protein is lost upon digestion of the histone tails by trypsin. The nucleosomal binding sites of the peptide appear identical to those of the intact protein. Thus, a region of the protein can acts as an independent functional domain. This supports the notion that HMG-14 and HMG 17 are modular proteins. This finding is relevant to the understanding of the function and evolution of HMG-14/-17, the only nucleosome core particle binding proteins known to date. PMID- 1453456 TI - Two tRNA-binding sites in addition to A and P sites on eukaryotic ribosomes. AB - The interaction of tRNA with 80 S ribosomes from rabbit liver was studied using biochemical as well as fluorescence techniques. Besides the canonical A and P sites, two additional sites were found which specifically bind deacylated tRNA. One of the sites is analogous to the E site of prokaryotic ribosomes, in that binding of tRNA is labile, does not depend on codon-anticodon interaction, does not protect the anticodon loop from solvent access, and requires the presence of the 3'-terminal adenosine of the tRNA. In contrast, the stability of the tRNA complex with the second site (S site) is high. tRNA binding to the S site is also codon-independent; nevertheless, the anticodon loop is shielded from solvent access. Removal of the 3'-terminal adenosine decreases the affinity of tRNA(Phe) for the S site approximately 50-fold. tRNA(Phe) is retained at the S site during translocation and through poly(Phe) synthesis. Thus, the S site does not seem to be an intermediate site for the tRNA during the elongation cycle. Rather, the tRNA bound to the S site may allosterically modulate the function of the ribosome. PMID- 1453457 TI - Substitutions of hydrophobic amino acids reduce the amyloidogenicity of Alzheimer's disease beta A4 peptides. AB - The deposition of amyloid protein aggregates in brain is the main pathological feature of Alzheimer's disease. Their principal constituent is a peptide termed beta A4, which comprises up to 43 amino acid residues. It is highly insoluble under physiological conditions and aggregates into filaments that form very dense clusters in vivo and in vitro. Based on a beta A4 prototype sequence spanning residues 10 to 42 or 43, we have designed analogues in which hydrophobic amino acid residues in position 17 to 20 were substituted by more hydrophilic residues. Depending on the kind of newly introduced amino acids and their position within the sequence, the substitution of only two residues led to variants exhibiting a broad spectrum of different properties. Common to them was a reduced beta-sheet content after solubilization in water and in the solid state. Some of the variants showed significantly reduced amyloidogenicity: although still forming filaments, they did not aggregate into the highly condensed depositions that are typical for amyloid. In addition, they could be solubilized in 200 mM-NaCl and KCl. When mixed with beta A4 peptides bearing the natural sequence, two of the analogues could inhibit the formation of filaments in vitro. These results demonstrate that a well-preserved hydrophobic core around residues 17 to 20 of beta A4 is crucial for the formation of beta-sheet structure and the amyloid properties of beta A4. The introduction of structural alterations within this region may guide the development of reagents for the therapy of Alzheimer's disease. PMID- 1453458 TI - Structure of the myosin filaments of relaxed and rigor vertebrate striated muscle studied by rapid freezing electron microscopy. AB - Rapid freezing followed by freeze-substitution has been used to study the ultrastructure of the myosin filaments of live and demembranated frog sartorius muscle in the states of relaxation and rigor. Electron microscopy of longitudinal sections of relaxed specimens showed greatly improved preservation of thick filament ultrastructure compared with conventional fixation. This was revealed by the appearance of a clear helical arrangement of myosin crossbridges along the filament surface and by a series of layer line reflections in computed Fourier transforms of sections, corresponding to the layer lines indexing on a 43 nm repeat in X-ray diffraction patterns of whole, living muscles. Filtered images of single myosin filaments were similar to those of negatively stained, isolated vertebrate filaments and consistent with a three-start helix. M-line and other non-myosin proteins were also very well preserved. Rigor specimens showed, in the region of overlapping myosin and actin filaments, periodicities corresponding to the 36, 24, 14.4 and 5.9 nm repeats detected in X-ray patterns of whole muscle in rigor; in the H-zone they showed a disordered array of crossbridges. Transverse sections, whose Fourier transforms extend to the (3, 0) reflection, supported the view, based on X-ray diffraction and conventional electron microscopy, that in the overlap zone of relaxed muscle most of the crossbridges are detached from the thin filaments while in rigor they are attached. We conclude that the rapid freezing technique preserves the molecular structure of the myofilaments closer to the in vivo state (as monitored by X-ray diffraction) than does normal fixation. PMID- 1453459 TI - Characterization of bacteriophage T7 RNA polymerase by linker insertion mutagenesis. AB - Thirty-four mutants of phage T7 RNA polymerase (RNAP) were generated by linker insertion mutagenesis and characterized with respect to their ability to carry out various steps in the transcription cycle. A number of mutants with interesting biochemical properties were identified. These include: (1) Mutant RNAPs that are catalytically active but that bind weakly to a T7 promoter; one of these mutants is affected in a region of the RNAP that exhibits homology with the sigma subunit of Escherichia coli RNAP. Another is affected in a region that has been previously implicated in the discrimination of T7 versus T3 promoters (Joho, et al., 1990). (2) Mutant RNAPs that can bind to the promoter but are transcriptionally inactive; some of these RNAPs lack catalytic activity, others are catalytically active but are unable to initiate productive transcription at a T7 promoter. Among the latter class of mutants are enzymes that appear to be weakened in their ability to melt open (or to remain associated with) double stranded DNA; these RNAPs make only abortive initiation products and are unable to proceed to the formation of a productive elongation complex. The mutations causing this phenotype affect regions of the RNAP that exhibit homology with the catalytic site of DNA polymerase I (Delarue et al., 1990). (3) A C-terminal insertion mutant with properties similar to a previously characterized "foot" mutant (Mookhtiar et al., 1991). This RNAP appears to be defective in the very early steps of transcription and may be unable to translocate and/or empty the active site. (4) A mutant that is transcriptionally active, but is unable to complement the growth of T7 gene 1- phage. This phenotype may result from disruption of a function of the RNAP that is distinct from its role in RNA synthesis. PMID- 1453460 TI - Substitution of a single bacteriophage T3 residue in bacteriophage T7 RNA polymerase at position 748 results in a switch in promoter specificity. AB - The bacteriophage T3 and T7 RNA polymerases (RNAP) are closely related, yet exhibit high specificity for their own promoter sequences. In this work the primary determinant of T7 versus T3 promoter specificity has been localized to a single amino acid residue at position 748 in the T7 RNAP. Substitution of this residue (Asn) with the corresponding residue found in T3 RNAP (Asp) results in a switch in promoter specificity, and specifically alters recognition of the base pairs (bp) at positions -11 and, possibly, -10 in the promoter. A complementary mutation in T3 RNAP (T3-D749N) results in a similar switch in promoter preference for that enzyme. The hierarchy of bp preference by the mutant and wild-type enzymes for bp at -10 and -11, and the results of previous experiments, lead to a model for specificity in which it is proposed that N748 in T7 RNAP (and D749 in T3 RNAP) make specific hydrogen bonds with bases at -11 and -10 on the non template strand in the major groove. The specificity determining region of T7 RNAP does not appear to exhibit homology to any known sequence-dependent DNA binding motif. PMID- 1453461 TI - Structure of the U2 strain of tobacco mosaic virus refined at 3.5 A resolution using X-ray fiber diffraction. AB - The structure of the U2 strain of tobacco mosaic virus (TMV) has been determined by fiber diffraction methods at 3.5 A resolution, and refined by a combination of restrained least-squares and molecular dynamics methods to an R-factor of 0.096. The structure is extremely similar to that of the common strain of TMV, with the largest differences being in the protein loop that makes up the inner surface of the virus, and in the C-terminal region on the outer surface. Differences in the inner loop can be correlated with differences in the properties of the two viruses. PMID- 1453462 TI - Is the bacteriophage lambda lysozyme an evolutionary link or a hybrid between the C and V-type lysozymes? Homology analysis and detection of the catalytic amino acid residues. AB - The relationship between the bacteriophage lambda lysozyme (lambda L) and the C and V-type lysozymes has been investigated by sequence alignment, secondary structure prediction and pattern recognition methods. The alignment of the amino terminal part of lambda L with that of V-type lysozymes suggests that Glu19 is a residue essential for catalysis. Its mutation to Gln leads to a completely inactive enzyme. In the alignment of the sequence of lambda L with those of the C type lysozymes a strongly homologous fragment of about 30 amino acid residues is detected. Taking into consideration this observation and the published structural alignments between C and V-type lysozymes, a repetition of the beta-sheet motif in lambda L is proposed. The multiple alignment draws the attention to a possible catalytic role for Asp34 that would be positioned in the middle of the second strand of the beta-sheet as in the C-type lysozymes. This role is confirmed by mutagenesis. The implications of these observations in terms of the evolutionary relationship between lambda L and the other lysozymes is discussed. PMID- 1453463 TI - Similarities and differences between human cyclophilin A and other beta-barrel structures. Structural refinement at 1.63 A resolution. AB - The structure of the unligated recombinant human cyclophilin A (CyP A) has been refined to an R-factor of 0.18 at 1.63 A resolution. The root-mean-squared deviations of the refined structure are 0.013 A and 2.50 degrees from ideal geometries of bond length and bond angle, respectively. Eight antiparallel beta strands of CyP A form a right-handed beta-barrel. The structure of CyP A is compared with other members in the antiparallel eight-stranded beta-barrel family and with the parallel eight-stranded alpha/beta barrels. Although all known eight stranded barrels are right-handed, the tilted angle of the strands against the barrel axis varies from 45 degrees for retinol binding protein and 49 degrees for CyP A to 70 degrees for superoxide dismutase. As a result, the beta-barrel of CyP A is not completely superimposable with other members of beta-barrels. The structure of CyP A has a unique topology, distinct from other members in the beta barrel family. In addition, CyP A is a closed beta-barrel so that neither the immunosuppressive drug cyclosporin A (CsA) nor the proline-containing substrate can bind to the hydrophobic core of the CyP A barrel, while the hydrophobic core of most other barrels is open for ligation. These observations probably indicate that CyP A is neither functionally nor evolutionally related to other beta-barrel structures. Details of interactions between solvent molecules and the active site residues of CyP A are illustrated. A water-co-operated mechanism, where the cis<- >trans isomerization might possibly consist of (1) transition of the prolyl bond and (2) release of N or C-terminal residues of substrate from CyP, is addressed. The refined structure reveals no disulfide bridges in CyP A. Cys115 is near the CsA site, but unlikely to be directly involved in CsA binding because of steric hindrance from Thr119 and Leu122. This geometry probably rules out any mechanisms involving a tetrahedral intermediate formed between cysteine and substrate during cis<-->trans isomerization. PMID- 1453464 TI - High resolution crystal structures and comparisons of T-state deoxyhaemoglobin and two liganded T-state haemoglobins: T(alpha-oxy)haemoglobin and T(met)haemoglobin. AB - The origin of co-operativity in haemoglobin (Hb) resides in the reduced affinity of the T-state. T-state Hb crystals grown from polyethyleneglycol can be liganded without the molecule switching to the R high affinity state. X-ray analysis of T state alpha-oxy Hb and T-state met Hb has identified the structural basis for reduced affinity. The nature of the chemical tension at the haem environment is different in the alpha and beta haems. There are small but definite structural changes associated with ligation in the T-state: these prove to be mostly in the same direction as the larger changes that occur in the T-->R transition. PMID- 1453465 TI - The crystal structure of the Bacillus lentus alkaline protease, subtilisin BL, at 1.4 A resolution. AB - The crystal structure of subtilisin BL, an alkaline protease from Bacillus lentus with activity at pH 11, has been determined to 1.4 A resolution. The structure was solved by molecular replacement starting with the 2.1 A structure of subtilisin BPN' followed by molecular dynamics refinement using X-PLOR. A final crystallographic R-factor of 19% overall was obtained. The enzyme possesses stability at high pH, which is a result of the high pI of the protein. Almost all of the acidic side-chains are involved in some type of electrostatic interaction (ion pairs, calcium binding, etc.). Furthermore, three of seven tyrosine residues have potential partners for forming salt bridges. All of the potential partners are arginine with a pK around 12. Lysine would not function well in a salt bridge with tyrosine as it deprotonates at around the same pH as tyrosine ionizes. Stability at high pH is acquired in part from the pI of the protein, but also from the formation of salt bridges (which would affect the pI). The overall structure of the enzyme is very similar to other subtilisins and shows that the subtilisin fold is more highly conserved than would be expected from the differences in amino acid sequence. The amino acid side-chains in the hydrophobic core are not conserved, though the inter-residue interactions are. Finally, one third of the serine side-chains in the protein have multiple conformations. This presents an opportunity to correlate computer simulations with observed occupancies in the crystal structure. PMID- 1453466 TI - Structure of oxidized bacteriophage T4 glutaredoxin (thioredoxin). Refinement of native and mutant proteins. AB - The structure of wild-type bacteriophage T4 glutaredoxin (earlier called thioredoxin) in its oxidized form has been refined in a monoclinic crystal form at 2.0 A resolution to a crystallographic R-factor of 0.209. A mutant T4 glutaredoxin gives orthorhombic crystals of better quality. The structure of this mutant has been solved by molecular replacement methods and refined at 1.45 A to an R-value of 0.175. In this mutant glutaredoxin, the active site residues Val15 and Tyr16 have been substituted by Gly and Pro, respectively, to mimic that of Escherichia coli thioredoxin. The main-chain conformation of the wild-type protein is similar in the two independently determined molecules in the asymmetric unit of the monoclinic crystals. On the other hand, side-chain conformations differ considerably between the two molecules due to heterologous packing interactions in the crystals. The structure of the mutant protein is very similar to the wild-type protein, except at mutated positions and at parts involved in crystal contacts. The active site disulfide bridge between Cys14 and Cys17 is located at the first turn of helix alpha 1. The torsion angles of these residues are similar to those of Escherichia coli thioredoxin. The torsion angle around the S-S bond is smaller than that normally observed for disulfides: 58 degrees, 67 degrees and 67 degrees for wild-type glutaredoxin molecule A and B and mutant glutaredoxin, respectively. Each sulfur atom of the disulfide cysteines in T4 glutaredoxin forms a hydrogen bond to one main-chain nitrogen atom. The active site is shielded from solvent on one side by the beta-carbon atoms of the cysteine residues plus side-chains of residues 7, 9, 21 and 33. From the opposite side, there is a cleft where the sulfur atom of Cys14 is accessible and can be attacked by a nucleophilic thiolate ion in the initial step of the reduction reaction. PMID- 1453467 TI - Adjacent zinc-finger motifs in multiple zinc-finger peptides from SWI5 form structurally independent, flexibly linked domains. AB - Peptides containing either one, two or three of the three zinc-finger motifs from the yeast transcription factor SWI5 have been prepared by expression in Escherichia coli. The DNA binding characteristics of these peptides were investigated, and a two-dimensional nuclear magnetic resonance (n.m.r.) study undertaken to establish the three-dimensional structures of the two-finger peptide. The peptide containing fingers 1 and 2 binds sequence specifically to two thirds of the DNA binding site recognized either by intact SWI5 or by the isolated three-finger peptide, and hence has the correct tertiary fold for DNA recognition. These results also establish the polarity of DNA binding, since the N-terminal two fingers of SWI5 bind to the 5' end of the DNA binding site. Mild proteolysis of the three-finger peptide using trypsin results in a small number of discrete products, which is consistent with the presence of three structured mini-domains. Nearly complete n.m.r. signal assignments were obtained for two peptides containing finger 2 alone or fingers 1 + 2. Comparison of two dimensional spectra of these peptides and others clearly shows that the NOE enhancements and chemical shifts characteristic of each finger are quite insensitive to the presence or absence of neighbouring fingers. This clearly indicates that adjacent zinc-finger domains are structurally independent in these peptides from SWI5. However, there must be some steric limitations on the possible relative orientations of the fingers, and to establish limits for these a set of structures for the peptide containing fingers 1 + 2 was calculated using the YASAP simulated annealing protocol in conjunction with n.m.r.-based constraints. A more detailed description of the three-dimensional structures of finger 1 and finger 2, and their relationship to other previously determined structures of single zinc-fingers, is given in the accompanying paper. PMID- 1453468 TI - Solution structures of two zinc-finger domains from SWI5 obtained using two dimensional 1H nuclear magnetic resonance spectroscopy. A zinc-finger structure with a third strand of beta-sheet. AB - This paper describes the detailed three-dimensional structures of two zinc-finger domains from the yeast transcription factor SWI5, calculated using the results of the n.m.r. experiments described in the accompanying paper. The structure of finger 2 is essentially similar to those previously obtained by others for isolated, synthetic single zinc-finger domains in solution, and for the three zinc-finger peptide Zif268 in its crystalline complex with DNA. The N-terminal half of the sequence forms a two-stranded, irregular beta-sheet containing both of the metal-binding cysteine residues, while the remainder of the structure forms a helix. Approximately the first half of this helix is alpha-helical, whereas the C-terminal portion, including the two metal-binding histidine residues, is 3(10) helical. Four invariant hydrophobic residues form a core to the structure. In contrast to all previously described structures of zinc-finger domains, finger 1 has an additional strand in the beta-sheet, formed by residues N-terminal to the formal start of the finger motif. This additional strand plays a role in stabilising the folded form of finger 1, since a two-finger peptide lacking the N-terminal residues showed folded structure in finger 2 but not in finger 1. PMID- 1453469 TI - Structural consequences of sequence patterns in the fingerprint region of the nucleotide binding fold. Implications for nucleotide specificity. AB - The dinucleotide binding beta alpha beta motif in the crystal structures of seven different enzymes has been analysed in terms of their three-dimensional structures and primary sequences. We have identified that the hydrogen bonding of the adenine ribose to the glycine-rich turn containing the fingerprint sequence GXGXXG/A occurs via a direct or indirect mechanism, depending on the nature of the fingerprint sequence but independent of coenzyme specificity. The major determinant of the type of interaction is the nature of the residue occupying the last position of the above fingerprint. In the NAD(+)-linked dehydrogenases, an acidic residue is commonly used to form important hydrogen bonds to the adenine ribose hydroxyls and, hitherto, this residue has been thought to be an indicator of NAD+ specificity. However, on the basis of the three-dimensional structure of the NAD(+)-linked glutamate dehydrogenase (GDH) from Clostridium symbiosum we have demonstrated that this residue is not a universal requirement for the construction of an NAD+ binding site. Furthermore, considerations of sequence homology unambiguously identify an equivalent acidic residue in both NADP+ and dual specificity glutamate dehydrogenases. The conservation of this residue in these enzymes, coupled to its close proximity to the 2' phosphate implied by the necessary similarity in three-dimensional structure to C. symbiosum GDH, implicates this residue in the recognition of the 2' phosphate either via water mediated or direct hydrogen-bonding schemes. Analysis of the latter has led us to suggest that two patterns of recognition for the 2' phosphate group of NADP(+) binding enzymes may exist, which are distinguished by the ionization state of the 2' phosphate. PMID- 1453470 TI - Three-dimensional structure of the high-potential iron-sulfur protein isolated from the purple phototrophic bacterium Rhodocyclus tenuis determined and refined at 1.5 A resolution. AB - The molecular structure of the high-potential iron-sulfur protein (HiPIP) isolated from the phototrophic bacterium, Rhodocyclus tenuis, has been solved and refined to a nominal resolution of 1.5 A with a crystallographic R-factor of 17.3% for all measured X-ray data from 30 A to 1.5 A. It is the smallest of the HiPIP structures studied thus far with 62 amino acid residues. Crystals used in the investigation belonged to the space group P2(1) with unit cell dimensions of a = 36.7 A, b = 52.6 A, c = 27.6 A and beta = 90.8 degrees and contained two molecules per asymmetric unit. The structure was solved by a combination of multiple isomorphous replacement with two heavy-atom derivatives, anomalous scattering from the iron-sulfur cluster, symmetry averaging and solvent flattening. The folding motif for this HiPIP is characterized by one small alpha helix, six Type I turns, an approximate Type II turn and one Type I' turn. As in other HiPIPs, the iron-sulfur cluster is co-ordinated by four cysteinyl ligands and exhibits a cubane-like motif. These cysteinyl ligands are all located in Type I turns. The hydrogen bonding around the metal cluster in the R. tenuis protein is similar to the patterns observed in the Chromatium vinosum and Ectothiorhodospira halophila HiPIPs. Several of the amino acid residues invariant in the previously determined C. vinosum and E. halophila structures are not retained in the R. tenuis molecule. There are 13 solvent molecules structurally conserved between the two R. tenuis HiPIP molecules in the asymmetric unit, some of which are important for stabilizing surface loops. Interestingly, while it is assumed that this HiPIP functions as a monomer in solution, the two molecules in the asymmetric unit pack as a dimer and are related to each other by an approximate twofold rotation axis. PMID- 1453471 TI - Crystallization and preliminary X-ray diffraction analysis of the catalytic domain of Cex, an exo-beta-1,4-glucanase and beta-1,4-xylanase from the bacterium Cellulomonas fimi. AB - Single crystals of the catalytic domain of Cex, an exo-beta-1,4-glucanase and beta-1,4-xylanase from the cellulolytic bacterium Cellulomonas fimi, have been grown in the presence of polyethylene glycol 4000 using the vapour diffusion technique. The crystals, which diffract to better than 2.0 A resolution, belong to space group P4(1)2(1)2 or P4(3)2(1)2 and have cell constants: a = b = 88.21 A, c = 81.10 A; alpha = beta = gamma = 90 degrees. PMID- 1453472 TI - Crystallization of recombinant chitobiase from Serratia marcescens. AB - We are currently investigating the biochemical and structural properties of both chitin degrading enzymes chitinase and chitobiase from Serratia marcescens. Previously we have reported the first crystallization and characterization of chitinase crystals (Vorgias et al., 1992). In this communication we present the first crystallization of chitobiase. The protein was synthesized in Escherichia coli and purified to homogeneity using cation exchange chromatography and fast protein liquid chromatography. The crystals have the shape of small prisms and the space group is P2(1) with beta = 101.0 degrees and unit cell dimensions a = 63.2 A, b = 133.2 A, c = 55.1 A. They diffract X-rays to about 2.5 A resolution and are suitable for three-dimensional structural analysis. PMID- 1453473 TI - A myoglobin evolved from indoleamine 2,3-dioxygenase. AB - Hemoglobins and myoglobins are some of the best studied proteins. They are distributed in animals, plants and bacteria, and the characteristic two intron three exon structure is widely conserved in animal globin genes (Jhiang et al., 1988). To date, all of the hemoglobins and myoglobins are believed to have a common origin, and so they are considered to be homologous. We have isolated a completely new type of myoglobin from the red muscle of the abalone Sulculus diversicolor aquatilis. The myoglobin consists of an unusual 41 kDa polypeptide chain, contains one heme per chain and forms a homodimer under physiological conditions. The cDNA-derived amino acid sequence of Sulculus myoglobin showed no significant homology with any other globins, but, surprisingly, showed high homology (35% identity) with human indoleamine 2,3-dioxygenase, a tryptophan degrading enzyme containing heme. This clearly indicates that Sulculus myoglobin evolved from a gene for indoleamine dioxygenase, but not from a globin gene. Sulculus myoglobin lacks the enzyme activity of indoleamine dioxygenase. However, in the presence of tryptophan, the autoxidation rate of oxymyoglobin was greatly accelerated, suggesting that a tryptophan binding site remains near or in the heme cavity as a relic of the molecular evolution. PMID- 1453474 TI - Differential expression of the presynaptic protein SNAP-25 in mammalian retina. AB - We have studied the expression of the nerve terminal protein synaptosomal associated protein 25 (SNAP-25) in the retina of adult rat, mouse, and monkey, as well as in the developing mouse retina. To evaluate SNAP-25 expression, its distribution was compared to those of the synaptic vesicle-associated proteins synapsin I and synaptophysin. In situ hybridization in adult rat retinas suggested that SNAP-25 mRNA is mainly expressed by ganglion, amacrine, and horizontal cells, but not by photoreceptors and bipolar cells. In all species, the SNAP-25 polypeptide was most abundant in the inner part of the inner and outer plexiform layers and was also found in the ganglion cell axons. In adult retina, synapsin I and synaptophysin were also mainly localized in synaptic fields and processes but all three proteins showed a distinct pattern of distribution. Finally, in mouse retina, the three proteins were first detectable at embryonic day 16 and subsequently showed developmentally regulated changes in their cellular localization. These results suggest that SNAP-25 is predominantly expressed in specific subtypes of conventional synapses, but not ribbon synapses, and that it may also be involved in the physiology of nonvesicular terminals of horizontal cells. Our study also suggests that combinatorial expression of different components of the presynaptic specialization may contribute to synaptic functional diversity. PMID- 1453475 TI - Receptor neuron losses result in decreased cytochrome P-450 immunoreactivity in associated non-neuronal cells of mouse olfactory mucosa. AB - Immunohistochemical and immunoblot analyses were used to investigate nasal cytochrome P-450 distribution in mice with either unilateral naris closure for 3, 4, or 5 months, or olfactory bulbectomy. P-450 immunoreactivity was observed only in the supporting cells and Bowman's glands of the olfactory mucosa. Immunoreactivity was clearly reduced in rostral regions of the open-side olfactory mucosa where losses of receptor neurons resulted from 3 to 5 months of closure. Closed-side immunoreactivity was similar to controls. In 4 month closure animals that had regrown their receptor neurons, open-side immunoreactivity was comparable to controls. Olfactory bulbectomy also depressed P-450 immunoreactivity. These data suggest that presence or absence of receptor neurons markedly affects P-450 expression in nonneuronal cells of the olfactory mucosa. PMID- 1453476 TI - Changes in chromatin proteins during optic nerve regeneration in the goldfish. AB - Regeneration of the goldfish optic nerve involves massive changes in the structure and pattern of macro-molecular synthesis in the retinal ganglion cells. To explore the mechanisms that underlie these events, we investigated the changes in chromatin proteins during the course of regeneration. Three major retinal chromatin proteins, two with apparent molecular weights of 58 kDa (C1 and C2) and one at 51 kDa (C3), all having isoelectric points around 5.5, showed a fourfold increase in their synthesis and/or accumulation by 14 days of regeneration. Synthesis of C1 and C3 decreased by day 32, the time at which the axons have grown back to the optic tectum and have formed many of their synapses; synthesis of C2 remained high through day 32. All three proteins bound to DNA-cellulose and required high salt concentrations (0.2-0.5 M KCl) to be eluted. C1 and C2 had similar proteolytic digestion patterns and reacted with monoclonal antibodies that recognize the goldfish intermediate filament proteins of the ON complex. The proteins identified here could be involved in structural alterations in the chromatin, or might serve as transcription factors to regulate gene expression during nerve regeneration. PMID- 1453477 TI - Taurine allosterically modulates flunitrazepam binding to synaptic membranes. AB - Taurine is hypothesized to exert its inhibitory neuromodulatory effects, in part, by interaction with the GABAA receptor. Although taurine displaces GABA agonist binding to synaptic membranes, its allosteric effects on the benzodiazepine recognition site of the GABAA receptor complex is unsettled. We determined the effects of taurine on [3H]flunitrazepam (Flu) binding to well-washed, frozen thawed synaptic membranes prepared from rat cortex. Comparative binding studies were conducted at 37 degrees C and on ice (0-4 degrees C). At 37 degrees C taurine increased Flu binding in a concentration dependent way by interaction with a bicuculline sensitive site, similar to GABA. Taurine increased Flu binding by causing a decrease in KD. The maximal effectiveness of taurine on Flu binding could not be increased further by addition of GABA. In contrast, the maximal stimulation of Flu binding by GABA was decreased by addition of taurine to the level attained by taurine alone. These mixed agonist/antagonist effects of taurine are pharmacologically specific and qualify taurine as a partial GABA agonist in this type of allosteric interaction. However, taurine causes opposite effects on Flu binding when measured at 0-4 degrees C: taurine interacts with a bicuculline insensitive site to inhibit Flu binding by increasing the KD. Taurine inhibition of Flu binding is not overcome by increasing concentrations of GABA. Although the mechanism of taurine inhibition of Flu binding at 0-4 degrees C is unclear, it may be an indirect effect of taurine interaction with membrane phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453478 TI - Cloning of a novel TGF-beta related cytokine, the vgr, from rat brain: cloning of and comparison to homologous human cytokines. AB - Here we describe cloning of a TGF-beta related cytokine from a rat brain cDNA library. This novel cytokine, the vgr (vegetal related), is homologous to the vegetal (Vg1) gene of Xenopus (DL Weeks and DA Melton, Cell, 51:861-867, 1987). In rat brain mRNA a single 3.5 kb RNA could be detected by Northern blot analysis. Thus, this new cytokine is constitutively expressed in the central nervous system. A monoclonal antibody reactive with a synthetic peptide of vgr revealed a faint vgr-like immunoreactivity throughout the CNS, with more pronounced staining of hippocampal neurons, ependymal cells, cells of the choroid plexus, and hypophysis. Using the rat cDNA, two homologous human cytokine cDNAs encoding the human vgr and op-1 were cloned. PMID- 1453479 TI - Neurofilament and tubulin mRNA expression in Schwann cells. AB - Feeding of elemental tellurium to weanling rats blocks synthesis of cholesterol (a major component of myelin), and causes demyelination of the sciatic nerve. Expression of mRNA for myelin-specific genes in Schwann cells is downregulated. We now demonstrate specificity for Schwann cell injury in that expression of mRNAs for neurofilament subunits and for class II beta-tubulin (parameters sensitive to axonal injury) is unaltered in neurons of the dorsal root ganglia. An unexpected result was that in tellurium-treated rats there was marked upregulation of expression of mRNAs coding for the light and medium neurofilament subunits ("neuron-specific" proteins) as well as that for class II beta-tubulin (the major neuronal beta-tubulin isotype) in Schwann cells. Expression of these "neuronal" mRNA species was also detected in distal stumps of transected nerves at times when Schwann cells were undergoing dedifferentiation. PMID- 1453480 TI - Differential expression of carboxyl terminal derivatives of amyloid precursor protein among cell lines. AB - Understanding the pathway for amyloid percursor protein (APP) catabolism has become an important line of investigation. APP is a ubiquitous membrane bound protein that is rapidly cleaved at the membrane, yielding a secreted protein identical to protease nexin II and an internalized 11.5 kDa 100 residue C terminal derivative (CTD). The levels of CTDs in a variety of cell lines have been examined and were found to differ. Cell types associated with the pathology of Alzheimer's disease (AD), such as olfactory neuroblasts (ON) and cortical vascular endothelial cells, have higher levels of CTDs than lymphoblasts and melanoma cells. The mechanism of CTD catabolism appears to involve the lysosome because blockade of lysosomal but not endosomal or mitochondrial function results in increased levels of CTDs. Under these conditions, production of larger, amyloidogenic CTDs is also seen. In cells possessing higher levels of CTDs we find that the mechanism for production of amyloidogenic CTDs may involve the internalization of intact full-length APP. Thus, inhibition of the lysosomal system appears capable of generating amyloidogenic peptides. The amount of amyloidogenic peptides appears to vary among cell lines. Such variation may shed light on why amyloid accumulates around specific cell types such as vascular endothelial cells, neurons, and glia. Finally, disfunction of the lysosomal system may play a role in the pathogenesis of Alzheimer's disease. PMID- 1453481 TI - Neuronal migration in cerebellar microcultures is inhibited by antibodies against a neurite outgrowth domain of laminin. AB - The functional role of laminin in neuronal migration was investigated by using polyclonal antibodies or their divalent (Fab')2 fragments to a neurite outgrowth promoting domain of the B2 chain of laminin in a cerebellar microculture system widely recognized as a model for neuronal migration. We show here that these antibodies or their (Fab')2 fragments totally inhibit migration of the mouse cerebellar granule cells along the glial and other neuronal cell processes. Antibodies to native laminin or other control antibodies have no inhibitory effect. Immunocytochemical analysis of the cerebellar microcultures indicates that the functional role of these antibodies may relate to the fact that the punctate deposits of laminin and its neurite outgrowth promoting domain accumulate in between the migrating neurons and the glial cells. These data provide the first direct evidence for the functional role of laminin and its neurite outgrowth domain in neuronal migration in the mammals. They further suggest that a neuronal cell surface contact with the extracellular deposits of a neurite outgrowth domain of the B2 chain of laminin may mediate neuronal-glial interactions. PMID- 1453482 TI - Myelin/oligodendrocyte glycoprotein is a unique member of the immunoglobulin superfamily. AB - Myelin/oligodendrocyte glycoprotein (MOG) is a primary target autoantigen in experimental autoimmune encephalomyelitis, a widely used animal model for autoimmune demyelinating diseases such as multiple sclerosis. We have isolated several rat MOG cDNAs and confirmed their identity by comparison with MOG N terminal peptide sequence. As expected, MOG mRNA expression is CNS-specific and peaks during active myelination. Our studies show that full length MOG mRNA is approximately 1.6 kb and encodes a signal peptide of 27 amino acids, followed by 218 residues for mature MOG (24,962 MW). A single site for N-glycosylation is found at Asn-31. Rather than the ubiquitous AAUAAA polyadenylation signal, a series of three overlapping, rare poly A signals were identified. The N-terminal half of mature MOG shares 52% identity with bovine butyrophilin, a possible lipid receptor. This same region has 39% identity with chicken B-G antigen, a major histocompatibility complex antigen involved in B cell selection and immune repertoire development. We show that both MOG and butyrophilin, each exhibiting a single Ig-like variable region domain, meet criteria for inclusion in the immunoglobulin superfamily. Moreover, MOG appears to represent a unique member of this superfamily in that it possesses two potential transmembrane domains, in contrast to a single membrane-spanning domain or glycophospholipid anchor found in all other members of Ig superfamily members. PMID- 1453483 TI - Intracellular calcium levels regulate the actions of nerve growth factor on calcium uptake in PC12 cells. AB - The uptake of divalent cations and the intracellular concentration of calcium in PC12 cells were studied by flow cytometric analysis using the calcium-sensitive dye, Fluo-3, under a variety of conditions. In particular the actions of nerve growth factor were analyzed. The data show that nerve growth factor stimulates the uptake of divalent cations and increases the intracellular calcium levels of cells attached to collagen-coated plates. The data further indicate that nerve growth factor-dependent increases in the uptake of divalent cations become less pronounced as the intracellular concentration of calcium increases. Intracellular calcium levels increase upon detachment of the cells from the plates and also with increasing cell density. Studies on the uptake of 45calcium confirmed the influence of intracellular calcium levels on nerve growth factor-stimulated calcium uptake. Thus, the effect of nerve growth factor on the uptake of divalent cations is dependent on the calcium levels in the cells, perhaps explaining why previous studies in this field have provided inconsistent results. PMID- 1453484 TI - Antibody to beta-amyloid precursor protein recognizes an intermediate filament associated protein in Alzheimer's and control fibroblasts. AB - The expression of beta-amyloid precursor protein (BAPP) and its mRNAs was studied in fibroblasts obtained from patients afflicted with Alzheimer's disease (AD) and age-matched controls. Using reverse transcriptase-polymerase chain reaction (RT PCR), transcripts corresponding to 770, 751, 714, and 695 amino acids were detected in both AD and control fibroblasts. Antibody 22C11 against BAPP (Boehringer Mannheim) labeled an intracellular protein, specifically localized to the intermediate filament network. In addition to bands of the predicted molecular weights for BAPP (120-135 kDa), Western blotting revealed a 57 kDa band which was not evident in samples of human brain. As cytoskeletal elements are vital in maintaining cellular architecture and various cell interactions, localization of BAPP or a related molecule to the cytoskeleton suggests a possible structural role for this protein within the cell. PMID- 1453485 TI - Cell cycle and proliferation dynamics of adult rat oligodendrocytes. AB - Adult oligodendrocytes (OLGs) have been shown to be mitotically responsive when co-cultured with dorsal root ganglion. We have investigated the population dynamics of the OLG proliferative response, including the maximum percent of cells which will proliferate and the cell cycle duration time of the adult rat OLG. Adult OLGs were stimulated with pituitary extract and either continuously labeled or pulse labeled with bromodeoxyuridine (BrdU). The labeled cells were stained with a fluorescent anti-BrdU monoclonal antibody, and fluorescence measurements were made with a multiparameter flow cytometer. A maximum number of 53% of the adult OLGs entered the cell division cycle after 9 days. The cell division cycle duration time (Tc) was determined to be approximately 35.4 hr, and the durations of G1, S, and G2M found to be 12.1, 8.5, and 5.8 hr, respectively. A scenario was generated for adult OLG proliferation in which 2.2% of the initial population is stimulated to enter the cell division cycle in the first 24 hr. This initial population divides and continues in the cell division cycle. Another 2.2% of the initial population enters the cell division cycle during the second 24 hr period, divides, and continues in the cell division cycle. This entry of 2.2% of the cells into the proliferative phase continues until 53% of the initial population has left a quiescent state and entered the cell cycle. PMID- 1453486 TI - Nerve growth factor (NGF) receptors in a central nervous system glial cell line: upregulation by NGF and brain-derived neurotrophic factor. AB - The neurotrophic proteins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are related in their primary amino acid structures. In this study we investigated the extent to which the low-affinity NGF receptor (LNGFR) in C6 glioma cells can discriminate between the neurotrophins NGF and BDNF. LNGFR-immunoreactivity (IR) was studied in C6 cells treated for 16 hr with NGF (50 ng/ml) or BDNF (10 ng/ml), using immunogold labelling and electron microscopic morphometric analysis. The cells were exposed to the anti-NGFR antibody 192-IgG, followed by immunoglobulin conjugated with colloidal gold. Untreated C6 cells exhibited some surface gold label (positive LNGFR-IR). Cells treated with NGF or BDNF displayed significantly increased LNGFR-IR on all surfaces in terms of gold labeling, which was more pronounced in NGF-treated cells. LNGFR-IR was also localized in coated endocytotic vesicles, in smooth endoplasmic reticulum, and in secondary multivesicular lysosomes in neurotrophin treated and untreated cells. The increase in LNGFR protein was further substantiated by a correspondingly higher content of LNGFR mRNA detected after 15 hr of either NGF or BDNF treatment. These results suggest that the LNGFR in glial cells can be upregulated by the structurally related neurotrophins NGF and BDNF. PMID- 1453487 TI - Beta/A4 domain of APP: antigenic differences between cell lines. AB - The expression of amyloid precursor protein (APP) in olfactory neuroblasts has been examined with a panel of antibodies directed against varied regions of the APP molecule. The pattern of reactivity was compared to that in the transformed human glial cell line SVG, human cortical brain tissue, and in kidney epithelial 293 cells containing stably transfected and overexpressed human APP751. Antibodies directed against the C-terminus and extracellular domains of amyloid precursor protein (APP) react more strongly on immunoblot with transfected 293 cells and brain tissue than with olfactory neuroblasts (ON) or SVG cells. Antibodies directed against the beta/A4 region of APP show a contrasting pattern of reactivity, yielding greater reactivity with ON and SVG cells than with transfected 293 cells or brain tissue. Analysis of the APP transcripts using polymerase chain reaction indicates that ON and SVG both make predominantly APP770 and 751, as does the transfected 293 cell line. In the absence of any differences in APP transcripts among the cell lines, the difference in availability of the beta/A4 region appears likely to be due to posttranslational modification. These data therefore indicate that processing of APP varies among cell lines and thus may vary from tissue to tissue. PMID- 1453488 TI - Effect of potassium and N-methyl-D-aspartate on the aspartate aminotransferase activity in cultured cerebellar granule cells. AB - The effect of potassium depolarization and N-methyl-D-aspartate (NMDA) on the activity of aspartate aminotransferase (AAT; EC 2.6.1.1), an enzyme suggested to be involved in neurotransmitter glutamate synthesis, was studied in cultured cerebellar granule neurons. Both KCl and NMDA increased AAT activity in a dose dependent manner. When cells were treated 48-72 hr with 40 mM KCl or 150 microM NMDA the AAT was enhanced about 65-75%. The EC50 for NMDA and KCl were 25 microM and 17 mM, respectively. The effect of NMDA and KCl was specific for AAT without affecting the activity of other enzymes like lactate dehydrogenase or protein content and it was observed only in granule cells but not in astrocytes or cortical neurons. The effect of KCl was not mediated by an activation of excitatory amino acid receptors and was Ca(++)-dependent. The effect of NMDA was completely blocked by Mg++ and NMDA antagonists. The increase of AAT induced by AAT and KCl was blocked by cycloheximide and actinomycin D, suggesting an involvement of de novo synthesis of proteins and RNA. Kainic acid and quinolinic acid were also effective in increasing the AAT activity. The action of kainate was less effective than that of NMDA and it was observed only at relatively low concentrations (10 microM). Quinolinic acid raised the activity of AAT about 45% at a concentration of 500 microM. Other non-NMDA agonists did not modify the AAT activity. From these findings we can conclude that NMDA and KCl exert a trophic action on cerebellar granular neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453489 TI - Regional distribution and biochemical characteristics of high molecular weight tau in the nervous system. AB - The present study examined the distribution of the high molecular weight (HMW) tau protein isoform in the nervous system by immunoblotting and immunohistochemistry. Some of the biochemical properties of this 110 kDa tau protein were explored, including its heat stability, phosphorylation and partitioning with cold/Ca2+ stable vs. soluble microtubules. Qualitative western blot analysis revealed that HMW tau is preferentially expressed in neurons with peripherally projecting axons. For example, this isotype was present in sciatic nerve, ventral and dorsal roots, trigeminal nerve, vagus nerve, dorsal root ganglia (DRG) and spinal cord, but was present in only trace amounts in CNS regions. Another tau isoform of slightly smaller size (90-100 kDa), termed mid molecular weight (MMW) tau, was present in abundant quantity in optic nerve samples and detectable in several other CNS regions, including hippocampus and cerebellum. The 110 kDa HMW tau as well as MMW tau and the other tau isoforms were found to be heat stable proteins. The HMW and MMW tau isoforms preferentially partitioned with the cold and Ca+2 insoluble tubulin fraction, but the association of HMW tau with stable microtubules was very susceptible to proteolysis. Dephosphorylation of fresh tissue with alkaline phosphatase produced no apparent shift in the mobility of HMW tau on SDS-PAGE but did alter the mobility of other brain tau isoforms, including MMW tau. Immunocytochemical staining with tau-1 antibody in the DRG, which contains HMW tau but no other tau isotypes, showed localization to mainly small neurons and was not altered by dephosphorylation of the histological sections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453490 TI - Time lapse study of neurite growth in hypothalamic dissociated neurons in culture: sex differences and estrogen effects. AB - Cultures of dissociated hypothalamic cells taken from rat fetuses of 19 days of gestation were studied using time-lapse recording and sequential microphotography from 1 to 5 days in vitro (DIV) and at 7 and 21 DIV. Cultures were seeded with cells taken from fetuses grouped by sex or sexually mixed; experimental cultures were raised in medium containing 17-beta-estradiol 100 nM (E2). Cells were plated on poly-D-lysine-coated coverslips at a culture density of approximately 4,000 cells/cm2. Immunocytochemistry of cell cultures was performed using a Tau monoclonal antibody (clone Tau-1 PC1C6) and a monoclonal antibody against MAP-2 (clone AP-20). Cells started to produce lamellipodia and neuritic processes approximately 4 hr after plating. Forty-eight hours later a few neurons had defined their morphological polarity by the differentiation of an axon-like process that grows faster than the others; at 5 DIV almost all neurons had defined their axons. At this time, monoclonal antibody against MAP-2 clearly stained soma and dendrites, but not axons. Tau immunoreactivity (lots CCA101 and CCA101N from Boeringher Mannheim) was differentially distributed, with a clear predominance in axon and soma. Results on the morphometric analysis of control and E2 treated neurons provide direct evidence for the existence of sex related differences in the neurite outgrowth response of hypothalamic neurons, since cultured neurons taken from female fetuses differentiated axons later and had fewer primary neurites and shorter dendrites than neurons taken from male fetuses or sexually mixed cultures. Also, it was demonstrated in living neurons that E2 effectively enhances outgrowth and elongation in axons. The frequency distribution curves of axonal length for control and E2 treated cultures was unimodal, suggesting that the effect of E2 was a uniform increase in the axonal length of all neurons. The structural differences between neurons from both sexes and the changes induced by E2 may contribute to explain the differences in brain function found between the sexes. PMID- 1453491 TI - Uptake and metabolism of malate in neurons and astrocytes in primary cultures. AB - Uptake and oxidative metabolism of [14C]malate as well as its incorporation into aspartate, glutamate, glutamine, and GABA were studied in cultured cerebral cortical neurons (GABAergic), cerebellar granule neurons (glutamatergic), and cerebral cortical astrocytes. All cell types exhibited high affinity uptake of malate (Km 10-85 microM) with slightly higher Vmax values in neurons (0.1-0.2 nmol x min-1 x mg-1) than in astrocytes (0.06 nmol x min-1 x mg-1). Malate was oxidatively metabolized in all three cell types with nominal rates of 14CO2 production of 2-15 pmol x min-1 x mg-1. The oxidation of malate was only slightly inhibited by 5 mM aminooxyacetic acid (AOAA). In granule cell preparations [14C]malate was incorporated into aspartate and glutamate and, to a much less extent, into glutamine. This incorporation was blocked by 5 mM AOAA. Astrocytes exhibited slightly higher incorporation rates into aspartate and glutamate, but in these cells glutamine was labelled to a considerable extent. AOAA (5 mM) inhibited the incorporation by 60-70%. In cultures of cerebral cortical neurons, very low levels of radioactivity derived from [14C]malate were found in aspartate and glutamate, and GABA was not labelled at all. Glutamine had the same specific activity as glutamate, indicating that the low rates of incorporation of radioactivity into amino acids in this preparation is likely to exclusively represent metabolism of malate in the small population of astrocytes (5% of total cell number), contaminating the neuronal cultures. The findings suggest that exogenous malate to a quantitatively limited extent may serve as a precursor for transmitter glutamate in glutamatergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453492 TI - Incorporation of 15N from L-leucine into isoleucine by rat brain cerebral cortex slices. AB - The fate of leucine nitrogen in the central nervous system was investigated by incubating rat cerebral cortex slices in the presence of 0.5 mM each of L-[15N] leucine, L-isoleucine, and L-valine. Analysis of the slices and incubation media for free amino acids by gas chromatography-mass spectrometry revealed that the 15N from leucine is incorporated into isoleucine only. No 15N was detected in valine or any other amino acid. These results suggest that leucine, valine, and their corresponding aminotransferases may be compartmentalized in brain cerebral cortex. PMID- 1453493 TI - Metabolic relationships between proteins of myelin and paranodally shedded, partially degraded myelin fragments in the rabbit CNS. AB - The "close-to-node" regions of myelinated nerve fibres, i.e., the paranodal end segments, are generally thought to be sites of high metabolic activity and myelin sheath turnover. Data on turnover rates of individual myelin constituents are conflicting but there exists a common belief that myelin is metabolized as independent molecules rather than as a unit. The occurrence of paranodal Marchi positive bodies, with morphological and biochemical properties consistent with partially degraded myelin, prompted us to examine the temporal dynamics of the incorporation of radioactive precursor label in the major proteins of myelin and the Marchi-positive bodies. 3H-leucine was administered intrathecally in adult rabbits. After various survival times, the spinal cord was subfractionated by ultracentrifugation in a discontinuous two-step 0.32 M/0.85 M sucrose gradient. Myelin was collected from the interface and a floating fraction, heavily enriched in Marchi-positive bodies, was recovered on top of the 0.32 M sucrose. By scintillation counting and by gel fluorography combined with immunoblotting, a gradual appearance with time of partially degraded peptides of myelin-associated protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase was seen in the floating fraction but not in myelin. The temporal dynamics of the specific activities of these two proteins and myelin-basic protein and proteolipid protein were consistent with a typical source-product relationship between myelin and the material in the floating fraction. In conjunction with earlier morphological and biochemical findings, these data may suggest that Marchi-positive bodies appear as a consequence of myelin catabolism. PMID- 1453494 TI - Evidence for intracellular cleavage of the Alzheimer's amyloid precursor in PC12 cells. AB - The Alzheimer's amyloid precursor (APP) is cleaved by an unidentified enzyme (APP secretase) to produce soluble APP. Fractionation of PC12 cell homogenates in a detergent-free buffer showed the presence of the Kunitz protease inhibitor (KPI) containing soluble APP (nexin II) in the particulate fraction. Digitonin or sodium carbonate treatment of this fraction solubilized nexin II suggesting that it is contained in the lumen of vesicles. Nexin II production was not affected by lysosomotropic agents, suggesting that APP secretase is not a lysosomal enzyme. Labelling of cell surface proteins by iodination failed to detect full-length APP on the surface of PC12 cells, suggesting that most of this protein is located intracellularly. Furthermore, pulse-chase experiments showed that nexin II is detected in cell extracts before it appears in the culture medium. Cellular nexin II was detected at zero time of chase after only 5 min of pulse labelling with 35S-sulfate, indicated that APP secretase cleavage takes place immediately after APP is sulfated. Temperature block, pulse-chase, and 35S-sulfate-labelling experiments suggested that APP is cleaved by APP secretase intracellularly in the trans-Golgi network (TGN) or in a post-Golgi compartment. PMID- 1453495 TI - Proliferation and differentiation of O4+ oligodendrocytes in postnatal rat cerebellum: analysis in unfixed tissue slices using anti-glycolipid antibodies. AB - We report the study of the in vivo morphology, differentiation, and proliferation of oligodendrocytes (OLs) and their progenitors identified by the antiglycolipid antibodies O4, R-mAb, and O1 in postnatal rat cerebellum, using a novel immunocytochemical staining protocol which allows the analysis of the expression of OL-specific glycolipids in live, unfixed brain slices. An analysis of the individual cells identified in double label immunocytochemistry indicated that the order of antigen expression in OLs during in vivo development is, first, antigens recognized by O4, second, antigens recognized R-mAb, and third, antigens recognized by O1. This order of antigen expression is correlated with increasing morphological complexity and is a pattern mimicked in many culture systems. In vivo O4 identified 3 distinct stages of the OL lineage: (1) morphologically simple proligodendrocyte antigen+ (POA+) R-mAb- blast cells localized at the leading edge of myelinogenesis; (2) morphologically more complex R-mAb+O1- cells; and (3) actively myelinating O1+ [i.e., galactocerebroside+ (GalC)] OLs residing within the white matter. Only the POA+R-mAb- cells incorporated BrdU in animals that were prelabeled 3 hr before immunocytochemistry. We have demonstrated in vivo the subdivision of pre-GalC+ OL progenitors into shorter, biologically noteworthy, stages of maturation. A spatial comparison of the cell populations identified by O4, R-mAb, and O1 demonstrated a progressive wave of OL maturation from the base of the cerebellum toward the folia. The data are consistent with the hypothesis that multiprocessed O4+GalC- progenitors are the most mature stage of the OL lineage with significant proliferative capacity and the first postmigratory stage in normal development. PMID- 1453496 TI - Urinary albumin determination by gel-filtration high-performance liquid chromatography. AB - To determine urinary albumin in a minute amount, a gel-filtration high performance liquid chromatographic procedure was newly established. When urine of a normal rat was eluted isocratically at 0.6 ml/min by 100 mM Na sulfate in 20 mM Na, K-phosphate (pH 7.4), approximately 6 hrs for complete elution of urinary peak-forming substances was needed. Retention time of albumin was found to be 22.9 min. To shorten the analytic time, 100 mM Na sulfate in 20 mM Na, K phosphate (pH 7.4) was first used during a 30 min period for separation of albumin. A mixture of acetonitrile/the above solvent = 3/7 (v/v) was then flushed to wash away the peak-forming substances. By this elution mode, the analytic time could be reduced to 3 hrs. When the validity of this procedure was tested, the detection limit of albumin was 0.04 microgram/injection, and a linearity was observed between 0.2 and 50 micrograms/injection. Rats then received single subcutaneous injections of puromycin aminonucleoside, which is a nephrotoxic agent. The plasma albumin concentrations fell at 5, 10 and 15 days after the administration, and the urinary excretions of albumin rose from the 1st day up to the 15th day. The results denoted that our procedure could be a good evaluative tool for nephrotoxicity studies where albuminuria was manifested. PMID- 1453497 TI - Toxicities of microencapsulated tribromomethane, dibromochloromethane and bromodichloromethane administered in the diet to Wistar rats for one month. AB - The gelatin-starch syrup microencapsulation method was applied to subacute toxicity studies of tribromomethane (TBM), dibromochloromethane (DBCM) and bromodichloromethane (BDCM). Groups of Wistar rats (7 males and 7 females) both sexes were given diet containing microcapsules of each of these trihalomethanes (THMs) at the following concentrations: TBM, 0.068, 0.204 and 0.612% in males, and 0.072, 0.217 and 0.651% in females; DBCM, 0.020, 0.062 and 0.185% in males, and 0.038, 0.113 and 0.338% in females; BDCM, 0.024, 0.072 and 0.215% in males, and 0.024, 0.076 and 0.227% in females. Suppression of body weight gain was seen in each high-dose males fed TBM or BDCM and females fed DBCM or BDCM. Histopathologically, hepatic lesions such as vacuolization and swelling of liver cells were significantly noted in both sexes of all groups fed TBM, in both sexes of the middle- and high-dose groups fed DBCM, and in males of the high-dose group and in females of the middle- and high-dose groups fed BDCM. In addition, single cell necroses were observed in males and females fed DBCM and in males fed BDCM. Hepatic cord abnormalities were also noted in males of the high-dose group fed BDCM. Although no increases in serum transaminase activities (ASAT, ALAT) were evident in either sex fed any of the THMs, decreases in triglyceride content, cholinesterase and lactate dehydrogenase activity were observed. Renal lesions reported to occur in gavage studies were not found in the present feeding study. Lowest-observed-adverse-effect-level (LOAEL) of TBM and no-observed-adverse effect-level (NOAEL) of DBCM and BDCM were determined to be 56.4 mg/kg, 18.3 mg/kg and 20.6 mg/kg, respectively, under the present experimental conditions. PMID- 1453498 TI - Effects of diethofencarb on thyroid function and hepatic UDP glucuronyltransferase activity in rats. AB - To examine the mechanism and toxicological significance of thyroidal tumor observed slightly in a long-term rat study with diethofencarb (isopropyl 3,4 diethoxycarbanilate), male Sprague-Dawley rats were fed diethofencarb in diets at concentrations of 0, 5,000 or 20,000 ppm for 3 months. Examinations mainly for thyroid functions including thyroid uptake of 125I, serum thyroid hormone and thyroid stimulating hormone (TSH) level, hepatic UDP-glucuronyltransferase (UDP GT) activity and histopathological examination in thyroid were performed at week 13. Decreases of body weights and food consumptions were observed at and above 5,000 ppm. Under these conditions, decrease of serum free T4 and increase of serum TSH level were observed only at 20,000 ppm, concurrently with liver weight increase at and above 5,000 ppm and increase of hepatic UDP-GT activity at 20,000 ppm. However, no compound related effects were noted in thyroid weight, thyroid uptake of 125I and gross or histopathological examination in thyroid. These results indicate that the administration of diethofencarb leads to an increase in UDP-GT activity and acceleration of thyroid hormone excretion from the liver. The acceleration causes a decrease in serum free T4 level, triggering the feedback mechanism of the pituitary gland, promotion of TSH release and consequently an increase in serum TSH level. Thus, the slightly higher incidence of thyroid follicular cell tumors observed in the chronic and oncogenicity study with non genotoxic diethofencarb is considered to be caused by these weak pituitary thyroid hormonal imbalances. The toxicological significance in humans is extremely low according to the well established facts that the chronic TSH stimulating would not induce thyroid tumors in humans and humans may be less sensitive than rats in regard to the response to goitrogenic stimuli. PMID- 1453499 TI - Effect of 1,25-dihydroxyvitamin D3 on the female reproductive system in rats. AB - Parenteral application of the active metabolite of vitamin D3, 1,25 dihydroxyvitamin D3, has been anticipated to have remarkable efficacy in secondary hyperparathyroidism. However, in a reproduction seg. I study in rats, poor reproductive performance was reflected in a decrease in the number of matings, implantations and live births. These changes were though reversible after treatment with the compound was discontinued. In order to clarify the mechanism of these reversible toxicities, the following were examined in female rats treated with the D3 metabolite: 1. effect on the estrous cycle (no treatment for 2 weeks, treatment for 3 weeks and recovery for 2 weeks), and 2. effect on the maintenance of pregnancy (treatment for 2 weeks before mating and during the gestation period). In both groups, the levels of calcium, calcitonin, PTH and progesterone in serum were measured, and histopathological examination of the thyroid, parathyroid, ovary and uterus was carried out. The following results were observed: 1) disturbance of the estrous cycle, 2) hypofunctional changes in the corpus luteum in the ovary, and the epithelium, endometrium and uterine gland in the uterus with a decrease in the serum progesterone level and 3) hypercalcemia with a decrease in calcitonin or PTH levels in serum with morphological changes including atrophy and cyst-formation in the parathyroid. However, the above changes were reversible, and recovery was observed after administration of the compound was discontinued. These results indicate that the hypercalcemia caused by 1,25-dihydroxyvitamin D3 disrupts endocrinological homeostasis which in turn temporarily disrupts the female reproductive system. Furthermore, it was suggested that 1,25-dihydroxyvitamin D3 itself directly influences on endocrinological organs (hypothalamus, pituitary, parathyroid and thyroid) and reproductive organs (ovary and uterus). PMID- 1453500 TI - [Role of mast cells in the development of liver fibrosis during experimental hepatocarcinogenesis in rats]. AB - The role of mast cells (MC) in the development of liver fibrosis during experimental hepatocarcinogenesis in rats has been studied light microscopically, histochemically and electron microscopically. An increase in the number of MC in the proliferated connective tissue was found. The histochemical examination showed that the increased MC almost exclusively were connective tissue mast cells (CTMC), whilst mucosa mast cells (MMC) were only rarely seen. The electron microscopical observation revealed a close topographical relationship between MC and fibroblasts sending out pseudopodia, which encircled granula released from MC and phagocytized them. The fibroblasts with phagocytized MC granules were markedly activated showing enhanced formation of collagenous fibrils. Finally, the role of MC in the development of liver fibrosis is discussed. PMID- 1453501 TI - Alteration in hypoxic pulmonary vasoconstriction during hypothermia in dogs. AB - This study was performed to investigate the pulmonary vascular reactivity during hypothermia. It was found that the pulmonary vessels were more sensitive to alveolar hypoxia in hypothermic dogs, and that hypoxic pulmonary vasoconstriction (HPV) was enhanced, which could be inhibited by alpha 1-adrenoceptor blocker prazosin. The concentration of arterial plasma norepinephrine (NE) increased in dogs with hypothermia or in those with hypothermia plus hypoxia, but there was no significant difference between these two groups. The plasma level of 5 hydroxytryptamine (5-HT) was reduced during hypoxia in hypothermic dogs. Increase in plasma 6-keto-PGF1 alpha, which appeared in hypoxic dogs, was not observed during hypoxia in hypothermic dogs. These findings suggest that a potentiation in the sensitivity and reactivity of alpha-adrenoceptor in pulmonary vessels and a decrease in the modulation of PGI2 might be responsible for the enhancement of HPV. 5-HT seemed not to play a contributing role in the alteration of HPV. PMID- 1453502 TI - The preventive effect of radix Salciae miltiorrhizae on monocrotaline-induced pulmonary hypertension in rats. AB - The preventive effect of Radix Salciae Miltiorrhizae (RSM) on pulmonary hypertension (PHT) and right ventricular hypertrophy (RVH) induced by monocrotaline (MCT) in rats was observed with the methods of measuring the right ventricular systolic pressure (PVSP), the ratio of the right ventricle to the left ventricle plus interventricular septum RV/(LV+S) and the pulmonary small artery morphological analysis. The results show that RSM can reduce the PHT, and prevent the RVH and the increase of the medial thickness of pulmonary small arteries. It can also prevent the endothelial cell injury produced by MCT. The pharmacological effects of RSM on pulmonary circulation were also discussed. PMID- 1453503 TI - Effects of sustained ligustrazine on hemorrheology in patients with chronic pulmonary heart disease. AB - Before and after oral administration of sustained Ligustrazine, changes of hemorrheology and TXA2/PGI2 were evaluated in 16 patients with advanced chronic pulmonary heart disease. A decrease in whole blood and plasma viscosity, and reductions in hematocrit and fibrinogen were found after one course of treatment with sustained Ligustrazine. The mechanism of these effects may be related to improved modulation of imbalance of TXA2/PGI2 in patients with advanced chronic pulmonary heart disease. PMID- 1453504 TI - Effect of "re du qing" on the activation, proliferation and membrane fluidity of lymphocytes. AB - Effects of Chinese Medicinal Preparation "Re Du Qing" (RDQ) on the activation, proliferation and membrane fluidity of T lymphocytes from human peripheral blood were studied by means of 3H-TdR incorporation and DPH fluorescence polarization. The results showed that "RDQ" can: 1) significantly inhibit the activation of T lymphocytes; 2) restrain the proliferation of activated T lymphoblasts in the presence of exogenous interleukin-2 (IL-2); and 3) increase the membrane fluidity of T lymphocytes and antagonize the decreased fluidity of lymphocyte membrane mediated by Con A or PHA. The functional abnormalities of T lymphocytes in some autoimmune diseases such as arthritis and the usefulness of RDQ in the treatment of these diseases were also discussed. PMID- 1453505 TI - Effects of surgical trauma on interleukin 2 production and interleukin 2 receptor expression. AB - To elucidate the mechanism of immunologic abnormalities induced by surgical trauma, we measured interleukin 2 (IL-2) production and IL-2 receptor expression in peripheral blood mononuclear cells from 16 patients with cholelithiasis. Compared with preoperative levels, IL-2 production and IL-2 receptor expression were significantly reduced on postoperative day 4, and the reduction was consistent with the suppression of lymphocyte proliferative response to phytohemagglutinin. PMID- 1453506 TI - Interleukin 2 production and its relationship with T lymphocyte subsets in patients with obstructive jaundice. AB - Sepsis remains a major risk in the high mortality and morbidity after surgery for obstructive jaundice. The reasons for the increased susceptibility to infection are unknown. This study examined interleukin 2 (IL-2) production and the lymphocyte response to PHA mitogen in 31 patients with obstructive jaundice. Among them, 18 patients were simultaneously investigated by enumeration of T lymphocyte subsets in peripheral blood with APAAP technique. The results showed that the patients had significantly decreased IL-2 production and lymphocyte response to PHA mitogen. The percentage of Leu 3a (helper/inducer T cell) in the patients was significantly lower than that in normal controls. Leu 3a/Leu 2a (suppressor/cytotoxic T cell) ratio was significantly lower in these patients. The reduction of IL-2 production correlated significantly with the suppression of lymphocyte proliferation but not with the percentage of Leu 3a cells. From these results, it may be suggested that the reduction of IL-2 production in the patients with obstructive jaundice is an important reason for the suppression of T lymphocyte proliferative response, not merely a reflection of the decrease of helper T cells. PMID- 1453507 TI - Gastromucosal lesions in rabbits with chronic schistosomiasis. AB - Upper gastrointestinal hemorrhage is one of the most important complications in portal hypertension secondary to schistosomiasis. Esophageal varices and gastric mucosal lesions are additional sources of bleeding. We studied the histologic and ultrastructural features of gastric mucosa in rabbits with chronic schistosomiasis (n = 10), with normal animals (n = 10) as controls. Our results confirm that in schistosomiasis, the gastric mucosa has characteristic functional and morphological features that may predispose it to the various damaging factors. Mucosal specimens reveal dilated submucosal vein with submucosal edema, ectasia of mucosal capillaries and venules. The mucosal vessels have conspicuous endothelial cells with prominent cytoplasm and numerous tiny projections extending into the vessel lumen. The submucosal venules show morphologic feature of arterialization. There are increased submucosal arteriovenous communications with a reduction in the effective mucosal blood flow. In addition, there are a number of eggs seen in the gastric mucosa of the rabbits with schistosomiasis. The granuloma may cause structural damage to the gastric mucosa. This finding suggests that schistosomiasis may play an important role in gastric lesions. PMID- 1453508 TI - Artificial bone of porous tricalcium phosphate ceramics and its preliminary clinical application. AB - The authors have prepared the artificial bone of porous tricalcium phosphate ceramics according to an appropriate formula and manufacturing technology. Physical and chemical testing shows that it possesses several distinguishing features: the communicating pores and macro/micropores; mean pore size, 380 microns (from 240 microns to 510 microns); porosity, 46.4%; and compressive strength, 97.4 kg/cm2. It consists of CaO (49.09%) and P2O5 (48.84%). The testing of its biocompatibility shows that it is devoid of systemic or local toxicity, and free of irritation or foreign body response in tissues, and it does not result in hemolysis or mutation. The new bone readily grows into its pores with direct contact to the implanted material. 11 cases of bone defects were treated with this artificial bone with satisfactory results. PMID- 1453509 TI - Detection of surface antigen expression of pre- and post-cultured normal adult's bone marrow cells by using ABC technique and its significance. AB - The expression of surface antigens on both normal adult's bone marrow and multipotential progenitor cells (CFU-Mix) was detected by use of ABC technique. The culture system of CFU-Mix was an ideal model for studying the differentiation direction of hematopoietic cells. The monoclonal antibodies (McAb) CD3, CD4, CD8 specific for T-lymphocytic lineage, CD22 for B-lymphocytic lineage and CD11, CD13, CD14 for granulocytomonocytic lineage were all demonstrated in certain proportion in cultured CFU-Mix, which might be associated with the control of hematopoiesis. A decrease in the positive rate of OKT9 and CD34 in cultured cells might be related to the differentiation of hematopoietic cells. SZ-2 and SZ-21 could contribute to the identification of the presence of megakaryocytes in CFU Mix. PMID- 1453510 TI - Clinical studies on high frequency two-way jet ventilation. AB - A new mode of jet ventilation, high frequency two-way jet ventilation (HFTJV) was devised and introduced to increase carbon dioxide elimination during jet ventilation. Its ventilatory efficiency and features were investigated and compared with those of high frequency jet ventilation (HFJV) in 10 patients with normal cardiopulmonary function. Random sample selection and randomized cross over trial were used for comparison between HFTJV and HFJV at the same ventilatory settings of driving pressure 1 kg/cm2 (14.22 Psi), respiratory rate 100/min and I/E ratio 1:2. Peak inspiratory pressure (PIP), end-expiratory pressure (EEP) and main variables of air blood gas analysis (PaO2, PaCO2, pH) were measured and recorded during the use of HFJV and HFTJV. PIP and EEP were significantly lower than with HFTJV than with HFJV. EEP of HFTJV showed a slightly negative pressure (-0.17 +/- 0.03 kPa). PaCO2 with HFTJV was significantly lower than that with HFJV, but PaO2 and pH with HFTJV were significantly higher than those with HFJV. HFTJV was shown to have a ventilatory feature of decreasing airway pressure and simultaneously increasing carbon dioxide elimination, as compared with HFJV. Whether this ventilatory feature of HFTJV can be utilized for various respiratory support in patients with abnormal cardiopulmonary function needs to be further studied. PMID- 1453511 TI - Echocardiographic estimate of left atrial pressure in children. AB - Echocardiographic estimates of left atrial pressure (LAP) using the Q-C/A2-E ratio were obtained from 40 patients and compared with directly recorded mean LAP and/or pulmonary wedge pressure (PWP). The best correlation was obtained between LAP and the Q-C/A2-E (gamma = 0.95, P < 0.01); a good one between PWP and the Q C/A2-E in normal and moderate pulmonary hypertension (gamma = 0.82, P < 0.01), but a poor one in severe pulmonary hypertension (gamma = 0.61, P > 0.05). Consequently, echocardiography provides a useful noninvasive method for the estimation of the LAP and PWP, particularly appropriate for children Intensive Care Unit. PMID- 1453512 TI - Tomorrow's gene therapy suggests plenteous, patent cardiac vessels. PMID- 1453513 TI - Additional dose urged for some receiving Haemophilus influenzae vaccine in early '90s. PMID- 1453514 TI - From the Congressional Office of Technology Assessment. PMID- 1453515 TI - From the Centers for Disease Control and Prevention. Surveillance for occupationally acquired HIV infection--United States, 1981-1992. PMID- 1453516 TI - From the Centers for Disease Control and Prevention. Chaparral-induced toxic hepatitis--California and Texas, 1992. PMID- 1453517 TI - From the Centers for Disease Control and Prevention. Nutritional needs surveys among elderly--Russia and Armenia, 1992. PMID- 1453518 TI - RBRVS gets an eye test. PMID- 1453519 TI - Pediatricians participating in Medicaid. PMID- 1453520 TI - Integrity in the National Resident Matching Program. PMID- 1453521 TI - Orienting college students to careers in medicine. PMID- 1453522 TI - Alcohol-related deaths of American Indians. PMID- 1453523 TI - Alcohol-related deaths of American Indians. PMID- 1453524 TI - Epidemiology of invasive pneumococcal infections in children in Finland. AB - OBJECTIVE: To study the epidemiologic characteristics of invasive infections in children caused by Streptococcus pneumoniae to provide background data for vaccination programs. DESIGN: A nationwide laboratory-based prospective surveillance of all invasive pneumococcal infections in children during 1985 through 1989. SETTING: A network of all microbiologic laboratories and pediatric wards in Finland. PATIENTS: Children aged 0 to 15 years who were admitted to a hospital with S pneumoniae isolated from blood, cerebrospinal fluid, or deep aspirate sample. RESULTS: Four hundred fifty-two invasive pneumococcal infections were diagnosed in 1985 through 1989. The annual incidence rate was 8.9 per 100,000 children less than 16 years of age (24.2 per 100,000 among children less than 5 years of age and 45.3 per 100,000 among those less than 2 years of age). The most common clinical entities were bacteremia without focus (310 cases), pneumonia (66 cases), and meningitis (51 cases), with other focal infections seen in 25 cases. The pneumococcal groups/types 14, 6, 19, 7, 18, and 23 comprised 78% of all invasive infections. CONCLUSIONS: Streptococcus pneumoniae is a common cause of invasive infections in children in Finland. A pneumococcal conjugate vaccine containing the six most common groups/types could prevent up to 70% of invasive pneumococcal infections of children in Finland if fully protective in infancy. PMID- 1453525 TI - Sex differences in osteoporosis in older adults with non-insulin-dependent diabetes mellitus. AB - OBJECTIVE: To describe the association of non-insulin-dependent diabetes mellitus (NIDDM) with bone mineral density (BMD). DESIGN: A survey of men and women from an established epidemiologic cohort who were separately screened for diabetes by oral glucose tolerance test between 1984 and 1987 and for osteopenia by BMD measured in 1988-1989. SETTING: A community-based population of older adults, Rancho Bernardo, Calif. PARTICIPANTS: The first 627 consecutively seen white men and women aged 55 to 88 years. MAIN OUTCOME MEASURES: Bone density measured by single photon absorptiometry at the ultradistal wrist and midradius and by dual x ray absorptiometry at the femoral neck and lumbar spine. MAIN RESULTS: Among the 236 men and 391 women, whose average age was 72 years, 41 men and 39 women had NIDDM, 56 men and 110 women had impaired glucose tolerance, and 139 men and 242 women had normal glucose tolerance. Men with diabetes had BMD levels similar to those men with normal glucose tolerance, whereas women with diabetes had significantly higher BMD levels at all sites than women with normal glucose tolerance. The increased bone density in diabetic women was unexplained by age, obesity, cigarette smoking, alcohol intake, regular physical activity, and the use of diuretics and estrogen. The multiply adjusted mean BMD in women with NIDDM compared with normoglycemic women was 0.600 g/cm2 vs 0.548 g/cm2 at the midradius; 0.265 g/cm2 vs 0.230 g/cm2 at the ultradistal wrist; 0.654 g/cm2 vs 0.610 g/cm2 at the femoral neck; and 0.962 g/cm2 vs 0.859 g/cm2 at the spine. The sex differences were unexplained by survivor bias, prior obesity, or duration of diabetes. Differences were seen in women (but not men) whose diabetes was first detected at the screening evaluation, ie, before drug or dietary treatment. Similarly, in women (but not men) without diabetes increasing BMD levels at all four sites were associated with increasing postchallenge glucose levels independent of age and body mass index. CONCLUSIONS: Older women with NIDDM or hyperglycemia had better BMD than women with normal glucose tolerance, independent of differences in obesity and many other risk factors. No differences in bone density by diabetic status were observed in men. We hypothesize that the sex differences may be explained by the greater androgenicity reported in women with hyperglycemic and hyperinsulinemic conditions. PMID- 1453526 TI - Confidential HIV testing and condom promotion in Africa. Impact on HIV and gonorrhea rates. AB - OBJECTIVE: We evaluated the impact of human immunodeficiency virus (HIV) testing and counseling on self-reported condom and spermicide use and on corresponding HIV seroconversion and gonorrhea rates in urban Rwandan women. DESIGN: Prospective cohort study with 2 years of follow-up, comparison of outcome variables before and after an intervention, and condom use measured in a control group that did not receive the intervention. SETTING: Outpatient research clinic in Kigali, the capital of Rwanda. PARTICIPANTS: One thousand four hundred fifty eight childbearing women, 32% of whom were infected with HIV, were enrolled in a prospective study in 1988, and followed at 3- to 6-month intervals for 2 years. Follow-up was available for 95% of subjects at year 1 and 92% at year 2. INTERVENTIONS: An acquired immunodeficiency syndrome (AIDS) educational videotape, HIV testing and counseling, and free condoms and spermicide were provided to all participants and interested sexual partners. MAIN OUTCOME MEASURES: Self-report of compliance with condom-spermicide use and observed incidence of HIV and gonorrhea. RESULTS: Only 7% of women reported ever trying condoms before the intervention, but 22% reported condom use with good compliance 1 year later. Women who were HIV-positive were more likely to adopt condom use than HIV-negative women (36% vs 16%; P < .05). Independent predictors of condom use, both in HIV-positive and in HIV-negative women, included HIV testing and counseling of the male partner, having a nonmonogamous relationship, and believing condoms were not dangerous. Human immunodeficiency virus seroconversion rates decreased significantly (from 4.1 to 1.8 per 100 person-years; P < .04) in women whose partners were tested and counseled. The prevalence of gonorrhea decreased substantially (13% to 6%; P < .05) among HIV-positive women, with the greatest reduction among condom users (16% to 4%; P < .05). CONCLUSION: A confidential HIV testing and counseling program was associated with increased use of condoms and reduced rates of gonorrhea and HIV in urban Rwandan women. The lack of risk reduction in HIV-negative women whose partner's serostatus was unknown was of concern. Interventions that promote HIV testing and counseling for both members of a couple should be considered in other high-prevalence areas. PMID- 1453527 TI - Academic-industry relationships in the life sciences. Extent, consequences, and management. AB - Academic-industry relationships in the life sciences remain controversial. The available evidence suggests that such relationships have both benefits and risks for involved parties. Benefits include additional support of academic research, income for academic health centers, the potential for increased scientific and commercial productivity in both industries and universities, and enhancement of the educational experiences of students and fellows. Risks include an increase in secrecy in academic environments and damage to public support for the life science enterprise. The balance of known benefits and risks suggests that academic-industry relationships should be permitted and even selectively promoted. However, there is also a need for enhanced vigilance on the part of academic institutions and government to reduce risks posed by certain types of arrangements, especially those involving human subjects. Enhanced vigilance should include disclosure of all academic-industry relationships by life science faculty. PMID- 1453528 TI - Invasive Haemophilus influenzae infections in men with HIV infection. AB - OBJECTIVE: To determine the incidence of invasive Haemophilus influenzae disease in men with the acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection and the proportion of disease due to serotype b. DESIGN: Population-based, active surveillance. SETTING: San Francisco (Calif) Department of Health. PARTICIPANTS: All men 20 to 49 years of age with invasive H influenzae disease. RESULTS: The cumulative incidences of invasive H influenzae disease in men 20 to 49 years of age with AIDS and in HIV-infected men 20 to 49 years of age without AIDS were 79.2 and 14.6 per 100,000, respectively, but only 33% of cases were due to serotype b. The corresponding rates for invasive H influenzae b disease were 11.3 and 7.6 per 100,000. CONCLUSIONS: Men with AIDS or HIV infection are at increased risk of invasive H influenzae infections, including H influenzae b, but such infections are still infrequent in this population. PMID- 1453529 TI - Newer tests for the diagnosis of renovascular disease. AB - OBJECTIVE: To evaluate published reports of diagnostic methods for renovascular hypertension, including Doppler ultrasonography, magnetic resonance imaging, the captopril test, and captopril scanning. DATA SOURCES: MEDLINE and selected references from appropriate published articles. STUDY SELECTION: Studies included those that calculated sensitivities and specificities; studies that derived diagnostic criteria without application to another population of patients were excluded. Consensus of both authors was necessary for inclusion. DATA EXTRACTION: Articles were critically assessed independently by the authors and a consensus critique was developed. DATA SYNTHESIS: Major sources of variability exist in the investigations of recently developed tests for renovascular hypertension. These include variability in patient populations, performance of tests, and determination of outcome measures. CONCLUSIONS: Among the newer diagnostic tests, both magnetic resonance imaging and Doppler ultrasonography hold promise for the anatomic detection of renal artery stenosis, but clear diagnostic criteria have not been universally accepted. There is more information concerning the captopril test, which has a sufficiently high sensitivity to be useful in the screening of high-risk patients for renovascular hypertension. Scans after captopril administration, which appear to be more specific, may enable the prediction of a blood pressure response to angioplasty or surgery. PMID- 1453530 TI - The resource-based relative value scale. PMID- 1453531 TI - New challenges in the development of a conjugate pneumococcal vaccine. PMID- 1453533 TI - The implications of the 1992 Presidential election for health care reform. PMID- 1453532 TI - AIDS in the global village. Why US physicians should care about HIV outside the United States. PMID- 1453534 TI - Clinical significance of reverse redistribution on thallium-201 single-photon emission computed tomography in patients with acute myocardial infarction. AB - To determine the clinical significance of reverse redistribution (RR), resting thallium-201 myocardial single-photon emission computed tomography was performed once or twice in 80 patients in subacute phase (1 week to 2 months) of myocardial infarction. Thirty eight patients demonstrated RR on at least one study (group RR) and 32 a fixed defect only (group FD). Group RR had significantly smaller defects than group FD. Standardizing the relation of the severity of wall motion abnormality of left ventricle on echocardiogram with that of perfusion defect, in group RR wall motion abnormality in the acute and subacute phase reflected the defect of delayed image, while that in chronic phase, which was thought to reflect the viability of myocardium in the infarct region, reflected the defect of initial image. In serial thallium-201 studies, only the defect of delayed image of group RR improved on the second study, while the defect of initial image of group RR and defect of group FD did not improve. Wall motion of group RR improved with the disappearance of RR, and when RR remained, wall motion did not improve so much. We concluded that RR was thought to be demonstrated in viable myocardium with severe wall motion abnormality. PMID- 1453535 TI - Right ventricular wall motion disturbance and determinants of the appearance of hemodynamic right ventricular infarction. AB - In order to elucidate the mechanisms of the appearance of hemodynamic right ventricular infarction (RVI), we studied right and left ventriculograms and hemodynamic findings in 52 patients with acute inferior myocardial infarction. Right ventricular wall motion disturbance (RVWMD) was detected in 69% of patient but hemodynamic RVI was observed only in 16%. Among patients with RVWMD, there was no significant difference in right ventricular ejection fraction between those with (group III) and without (group II) hemodynamic RVI, suggesting that right ventricular (RV) systolic dysfunction does not independently produce hemodynamic RVI. Right ventricular end-diastolic volume index was similar in groups II and III in spite of higher mRA in group III. The result suggested that the RV compliance of group III was decreased. Heart rate (HR) was significantly lower in group III than in group II. Not only physiologic pacing but also VVI pacing significantly improved hemodynamics in patients with hemodynamic RVI. A positive correlation between HR and cardiac index was observed (r = 0.56, p < 0.001) in patients with RVWMD. Decreased RV compliance and bradycardia were considered to be determinants of the appearance of hemodynamic RVI. Volume loading did not improve hemodynamics significantly in patients with hemodynamic RVI. PMID- 1453536 TI - Plasma catecholamine responses to dynamic exercise in patients with coronary artery disease--the relationship between sympathetic activity and systolic blood pressure and exercise-induced ventricular arrhythmias. AB - In order to investigate the relationship between sympathetic activity and postexercise systolic blood pressure (SBP) and exercise-induced ventricular arrhythmias in patients with coronary artery disease (CAD), we studied 38 patients and 9 normal subjects who underwent treadmill testing. Peak pressure rate product was similar in the 2 groups. The plasma concentrations of norepinephrine and epinephrine at rest and immediately after exercise were significantly higher in patients with CAD compared with normal subjects (norepinephrine at rest, p < 0.01; norepinephrine immediately after exercise, p < 0.05; epinephrine at rest, p < 0.05; epinephrine immediately after exercise, p < 0.05). The level of norepinephrine immediately after exercise was significantly higher in 15 patients with a postexercise SBP increase than in 23 patients without that SBP change (p < 0.05), whereas the level of epinephrine was similar in the 2 groups. The level of epinephrine immediately after exercise was significantly higher in 10 patients with exercise-induced premature ventricular contractions than in 28 patients without those arrhythmias (p < 0.05), whereas the level of norepinephrine was similar in the 2 groups. We conclude that a postexercise SBP increase is related to the augmentation of sympathoneural activity and that exercise-induced ventricular arrhythmias are related to the augmentation of sympathoadrenal activity. PMID- 1453537 TI - Improvement in long-term prognosis by coronary bypass surgery in patients with 3 vessel coronary disease--a matched case control study. AB - We compared survival patterns in 61 medically treated and 78 surgically treated patients at a Japanese community hospital. The 2 groups were matched for presence of significant 3 vessel disease, resting ejection fraction of more than 40%, a bypassable left anterior descending artery, sex, and age. All surgical patients received saphenous vein grafts. The patients treated surgically had better 5 and 9 years survival rates than the medically treated patients (93% and 85% vs 74% and 55%, respectively; p < 0.01 by Cox-Mantel analysis). Five and 9 years rates of absence of ischemic events (non-fatal myocardial infarction and primary cardiac death) were also better in the surgical group than the medical group (92% and 87% vs 66% and 52%, respectively; p < 0.001). Of the surgically treated patients, 5 died perioperatively, 3 had late cardiac deaths and 2 had a nonfatal infarction. Among the medically treated patients, 16 had cardiac deaths, and 6 had non-fatal infarctions. Although our study was non-randomized, we have shown an advantage for surgical treatment of patients with 3-vessel coronary disease. PMID- 1453538 TI - Effect of captopril on isoproterenol-induced cardiac hypertrophy and polyamine contents. AB - It is well known that isoproterenol (ISO) a nonselective beta adrenoceptor agonist induces cardiac hypertrophy. It can be assumed that, in addition to its direct cardiac effect, ISO has a cardiac trophic effect via stimulation of the renin angiotensin system. Synthesis of polyamines is facilitated in cardiac hypertrophy and polyamine levels are rapidly elevated prior to an increase in heart weight. In the present study, we investigated whether captopril (30 mg/kg body weight, daily) could attenuate cardiac hypertrophy and elevation of cardiac polyamine levels in rats, which effects were elicited by a chronic (1- or 2 weeks) and repeated administration of a small dose (0.5 mg/kg body weight) of ISO. Cardiac hypertrophy was assessed by an increase in the wet weight and RNA content of the heart. Polyamines were analyzed by HPLC. Captopril alone did not affect either heart weight/body weight ratio or cardiac contents of polyamines and nucleic acids at the end of the second week. In isoproterenol-treated rats, the above parameters, except for putrescine content on day 14, were significantly increased on both day 7 and day 14. Captopril slightly attenuated ISO-induced cardiac hypertrophy and significantly prevented the ISO-evoked increase in the contents of RNA, spermidine, and spermine at the end of the second week. These results suggest that the ISO-evoked increase in cardiac polyamines was mediated, at least in part, by the renin angiotensin system, which was stimulated by ISO. PMID- 1453539 TI - Pathogenesis, treatment and prognosis of impending myocardial infarction and early post-infarction angina--relation between ST-segment shift during myocardial ischemia and the pathogenesis. AB - We studied 141 patients to evaluate the pathogenesis and clinical picture of high risk unstable angina (UA), designated as impending myocardial infarction (IMI) in this study, or severe early post-infarction angina (PIA). IMI and PIA were diagnosed when chest pain appeared at rest and lasted 15 min or more despite extensive pharmacological therapy during hospital stay among consecutive 510 patients with UA. All patients underwent coronary angiography urgently within 72 h after chest pain, and were divided into 2 subgroups according to ST segment shifts during chest pain. In IMI, 42 patients with ST depression had higher incidences of prior myocardial infarction (MI), worsening UA, multivessel disease and complex lesions such as eccentric irregular lesion or ulceration. On the contrary, in 44 with ST elevation, new onset UA, single vessel disease and coronary thrombus (CT) were dominant. In PIA, 32 patients with ST elevation revealed higher incidences in Q wave MI, ST elevation at the MI onset, single vessel disease and CT, compared to 23 with ST depression who showed a high proportion of complex lesions. Thus, it was evident that there was a common link between the pathogenesis of IMI and PIA. The therapeutic options were also different in the groups according to ST segment shift. We conclude that ST segment shifts during chest pain may be useful for determining the pathogenesis and clinical features of high-risk UA. PMID- 1453540 TI - The pathogenesis of an impending infarction and its treatment--an angioscopic analysis. AB - To clarify the pathogenesis of an impending infarction and to investigate the difference between the pathogenesis of an acute myocardial infarction and an impending infarction, we have performed percutaneous transluminal coronary angioscopy in 13 patients with an impending infarction and in 13 patients with an acute myocardial infarction. As a result, coronary thrombi were observed in 12 of the 13 patients with an impending infarction, and a similar frequency of thrombi was observed in the patients with an acute myocardial infarction. Further, grayish white thrombi were observed in 9 of 12 patients with an impending infarction, but no such thrombi were noted in those with an acute myocardial infarction. Reddish thrombi, however, were observed in all patients with acute myocardial infarction, whereas such thrombi were observed in only 3 of 12 patients with an impending infarction. Informatively, occlusive thrombi occurred more frequently in patients with an acute myocardial infarction than in those with an impending infarction. As a thrombus plays an important role in an impending infarction, we also evaluated the effect of anticoagulant and thrombolytic therapy for an impending infarction in 79 patients. The incidence of recurrent angina and a subsequent acute myocardial infarction were significantly higher in non-heparin-treated patients and in thrombolytic-treated patients than in heparin-treated patients. In conclusion, a thrombus plays an important role in the pathogenesis of an impending infarction and in an acute myocardial infarction, though the characteristics of the thrombus differ in each instance. This difference may account for the differing results of thrombolytic therapy. Heparin was found an effective treatment for myocardial ischemia in an impending infarction. PMID- 1453541 TI - The response to drug therapy in unstable angina on the basis of coronary angiography findings. AB - Among 366 unstable angina pectoris patients at our hospital, myocardial infarction was common (15.7%) in those with attacks of chest pain lasting for at least 20 min. There was also a high incidence (30.3%) when chest pain continued after the start of inpatient treatment. To investigate the etiology of unstable angina, coronary arteriography was performed in both the unstable and stable stages in these patients and the results were compared. The role of coronary spasm and coronary thrombosis in unstable angina was investigated, and the efficacy of continuous infusion of either diltiazem or isosorbide dinitrate as treatment for these patients was compared. Coronary arteriography in the unstable stage showed, no clear differences in the morphology of the stenotic site and the degree of stenosis between the patients with and without infarcts when urokinase or isosorbide dinitrate were injected into the coronary arteries. When drug treatment was effective, the angina was stabilized without any improvement in the degree of stenosis or the morphology of the involved coronary vessel. Thus, it was difficult to predict the response to treatment from coronary arteriography performed in the unstable stage. Diltiazem was more effective than isosorbide dinitrate, and it appears that some action other than coronary dilatation was involved in achieving the remission of unstable angina. PMID- 1453542 TI - Coronary angiographic findings and in-hospital outcome of aggressive treatment in impending myocardial infarction. AB - The influence of coronary angiographic findings and treatment on clinical outcome was determined in 104 patients with impending myocardial infarction (unstable angina with prolonged chest pain and persistent electrocardiographic changes on admission). Coronary arteriography was performed on day one (aggressive strategy) in 50 patients and following medical treatment (conservative strategy) in 48 patients, of whom 40 were unstable. Six elderly patients were treated medically without angiography. A complex eccentric morphology of the coronary vessels was the most common finding in both groups, but the incidence of intracoronary thrombus was significantly higher in the aggressive strategy group (78%) and in unstable patients (77%) compared with patients controlled medically (24%). Severe multivessel disease was also common in refractory patients without thrombus. Percutaneous transluminal coronary angioplasty was less successful and produced more distal emboli in patients with thrombus. Emergency intervention was applied to 90% of the aggressive strategy group-it failed to improve the in-hospital outcome, but shortened hospitalization significantly. Elderly patients treated medically without angiography had the highest mortality. We concluded that intracoronary thrombus plays a major role in the pathogenesis of impending infarction, and that the majority of such patients cannot be stabilized medically. An aggressive strategy can be applied safely to impending infarction and will shorten hospitalization. PMID- 1453543 TI - Percutaneous transluminal coronary angioplasty for patients with unstable angina pectoris. AB - Percutaneous transluminal coronary angioplasty (PTCA) was successful in 91% of 76 patients with unstable angina pectoris refractory to pharmacological treatment. However, the rate of acute occlusion and reocclusion was rather high (95). Restenosis developed in 56.5% of successful cases after initial PTCA, and 29 patients underwent 2nd, and nine 3rd PTCA. Most refractory unstable angina can be controlled by PTCA, which may require repeating in some patients. PMID- 1453544 TI - Experimental evaluation of coronary thrombodynamics and effects of pharmacological interventions in acute coronary syndromes. AB - Intracoronary thrombodynamics in acute coronary syndromes was studied with an experimental canine model. An intracoronary thrombus was precipitated at the mock ruptured atheromatous plaque consisting of cholesterol and collagen. In 8 of 10 control models, acute myocardial infarction (AMI) was induced by intracoronary occlusive thrombus 1 h after the start of the experiment. Coronary blood flow decreased continuously (Type A, n = 5) or cyclically (Type B, n = 3) to end in AMI. Effects of pharmacological interventions to prevent AMI were also studied with the model. An intravenous bolus injection of a thromboxane synthetase inhibitor (RS-5186), heparin, a thrombin inhibitor (argatroban), and a thrombolytic agent (urokinase) was performed in 10 models for each drug. The incidence of AMI was significantly decreased to 3 of the 10 models injected with the thromboxane synthetase inhibitor and heparin (p < .05, each drug group vs. control). The preventive effect of argatroban was more potent and AMI occurred in 2 of 10 models (p < 0.01, argatroban vs control). PMID- 1453545 TI - Effect of the combination of anticoagulant and thromboxane synthetase inhibitor (Y-20811) or receptor blockade (S-1452) on preventing thrombotic cyclic coronary flow reduction in dogs with coronary stenosis. AB - We examined the hypothesis that combined actions of anticoagulant (heparin) and Y 20811, thromboxane A2 synthetase inhibitor (TXSI), or S-1452, receptor blockade (TXRB), can provide better antithrombotic protection than TXSI or TXRB alone. In 20 of 33 dogs instrumented, placement of a critical stenosis at a focus of coronary vascular injury initiated a reproducible cyclic coronary flow reduction (CCFR). TXSI (1 mg/kg, IV) perfectly inhibited CCFR in 6 of 10 dogs (60%), and was associated with a significant decrease in 11-dehydro-TXB2 (85 +/- 8% of control; p < 0.05) and an increase in 6-keto-PGF1 alpha (155 +/- 38%; p < 0.05) in coronary sinus blood samples. In the remaining 4 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. On the other hand, TXRB (1 mg/kg, IV) perfectly inhibited CCFR in 7 of 10 dogs (70%), and was accompanied by a significant increase in 6-keto-PGF1 alpha (214 +/- 65%; p < 0.05) and unchanged TXB2 level. In the remaining 3 dogs, additional administration of heparin (2000 IU) completely abolished CCFR. Thus, the combination of anticoagulant and TXSI or TXRB were more effective than TXSI or TXRB alone in abolishing thrombotic CCFR, suggesting that the combination might be effective for treating patients with impending myocardial infarction. PMID- 1453546 TI - Are the various thrombolytic agents equally effective in the treatment of acute transmural myocardial infarction? AB - While it is no longer possible to imagine the treatment of an acute transmural myocardial infarction without the use of thrombolytic agents, some discussion still exists as to the choice of the thrombolytic agent. Our study concerns a group of 160 patients with an acute transmural myocardial infarction, 60 of whom were treated with anistreplase, 52 with streptokinase and 48 with alteplase. Statistically, the administration of anistreplase was associated with a significantly higher frequency of ventricular arrhythmias in comparison to the other thrombolytic agents, whereas after subsequent coronary angiography, the anistreplase group revealed a significantly lower number of completely occluded coronary arteries. The data from this study demonstrate that anistreplase is a very valuable thrombolytic agent. It may even be more effective than streptokinase and alteplase in the treatment of acute myocardial infarction when the patency of the coronary arteries 1 month after the acute coronary event is considered the primary endpoint. PMID- 1453547 TI - Early diagnosis of the site of infarction and the infarct-related coronary artery in patients with acute inferior myocardial infarction. AB - We evaluated the relationship between the site of infarction and the infarct related coronary arteries from electrocardiograms (ECGs) recorded early after the onset of chest pain in patients with an initial acute inferior myocardial infarction (IMI). The subjects were 80 patients (mean age 57 +/- 12 years) with IMI admitted within 6 hours from the onset of chest pain. This was prior to the thrombolytic era. We analyzed the ECGs on admission, at 24 hours and at 4 weeks. All patients underwent left ventriculography and coronary angiography at 4-6 weeks from the onset of the IMI. Left ventricular ejection fraction (EF) and regional area changes were measured. The infarct-related coronary artery was determined by the site of the asynergy. Patients were allocated into 2 groups according to the infarct-related artery, i.e. right (RCA, n = 52) and left circumflex (LCX, n = 28). Parameters measured were ST elevation, amplitude and width of R wave and R/S ratio in leads V1 and V2, and amplitude of U waves in leads V1 to V3. We defined the U wave as a prominent positive U wave (PPU) if it was > 0.5 mm (50 microV) in height. A significantly greater number of patients with PPU showed asynergy in posterolateral segments compared to those without PPU. The EF was significantly lower in patients with PPU than in those without (46 +/- 12% vs 54 +/- 13%, p < 0.05). Patients with PPUs eventually showed ECG evidence of posterior infarction (increased R wave duration and R/S ratio > or = 1 in lead V1 or V2) by 4 weeks compared to those without PPUs. Also a significantly greater number of patients with PPUs developed posterior infarction shown by left ventriculograms than those without PPUs. As to the infarct-related coronary arteries, a significantly greater number of patients with LCX disease showed concomitant posterior infarction than those with RCA disease. Also, a significantly greater number of LCX patients showed PPUs and ST elevations in leads V5 and V6 than those with RCA disease. The sensitivity of PPUs and ST elevations in leads V5 and V6 suggesting LCX disease was 60% and the specificity was 98% with a predictive accuracy of 87%. Therefore, we conclude that PPUs in leads V1-3 and ST elevations in leads V5 and V6 are specific markers for the diagnosis of LCX-related infarction in the setting of evolving IMI. PMID- 1453548 TI - Interventional intra-arterial ultrasonography as an exclusive method of exploration to determine atherosclerotic lesions of the arterial wall at a preclinical stage. AB - Intravascular ultrasonography of the peripheral arterial system was applied following coronarography in 56 patients with one or several critical stenoses of the coronary arteries. Even though the clinical vascular examination and the subsequent noninvasive examination of the peripheral arterial system of all these patients turned out to be completely normal, intra-arterial ultrasonography was able to reveal important atherosclerotic alterations in the wall of the abdominal aorta and of the iliac-femoral arterial system in 51 of these patients. Intra arterial ultrasonography appears to be a very sensitive method of exploration, permitting atherosclerotic changes of the arterial wall to be detected at a very early preclinical stage, long before these deviations could have caused symptoms. PMID- 1453549 TI - Plasma lipid profile in obese children and in children with hereditary predisposition to coronary heart disease. AB - This study examined risk factors for coronary disease and plasma triglycerides, total cholesterol, HDL, LDL cholesterol (C), Apo A-1, and Apo B lipoprotein levels in obese children (n = 107) aged 9-12 years old and in children (n = 64) hereditarily predisposed to coronary heart disease (CHD). In the latter group, children's fathers had a history of MI before 50 years of age. A control group of 30 children was also studied, and the plasma lipid profile was investigated in 35 fathers with premature myocardial infarction. Seventy-five percent of the obese children and 60% of the children hereditarily predisposed to CHD had three or more coronary artery disease risk factors. Plasma HDL-C (p < 0.001), LDL-C (p < 0.001-p < 0.05, respectively), Apo A-1 (p < 0.001), and Apo B (p < 0.001) levels were different in both groups compared with controls. PMID- 1453550 TI - Effects of pravastatin on cholesterol metabolism in Watanabe heritable hyperlipidemic rabbits. AB - Pravastatin, a competitive inhibitor of hydroxymethylglutaryl CoA reductase (HMG CoA reductase) is a potent hypocholesterolemic agent in humans as well as experimental animals, including the Watanabe heritable hyperlipidemic (WHHL) rabbit, lacking low density lipoprotein (LDL) receptor activity. We studied the effect of pravastatin on several aspects of cholesterol metabolism in WHHL rabbits. Cholesterol synthesis was measured by intraperitoneal injection of radioacetate and determination of its incorporation into the nonsaponifiable lipid fraction of liver, plasma, adrenal glands and gonads. A single dose of pravastatin (25 mg/kg) caused statistically significant inhibition of hepatic cholesterol synthesis at 2, 6, 12, and 24 hours following oral administration. By 48 hours, the inhibitory effect of the drug was no longer demonstrable. The pattern of radioactivity in the plasma was similar to that in the liver. The drug had no statistically significant effect on cholesterol synthesis in adrenal glands and gonads, suggesting a selective effect on the liver. Cholesterol absorption was studied after simultaneous oral administration of [3H] cholesterol and [14C] beta-sitosterol. Pravastatin, 50 mg/kg for 10 days had no effect on fecal excretion of the radiolabelled steroids over 4 days. At 24 hours the plasma level of [14C] cholesterol was 1/3 that of control in pravastatin treated animals (p < 0.05) but did not undergo an accelerated decline over 6 days. The activity of acyl CoA: cholesterol acyltransferase (ACAT) in intestinal mucosa and the concentration of hepatic cholesterol were similar in animals treated over one year with pravastatin 50 mg/kg/day or with placebo. Our data do not allow us to make definitive conclusions about the effect of pravastatin on cholesterol absorption but are compatible with the hypothesis that the drug inhibits the hepatic synthesis as well as the assembly of cholesterol into lipoproteins. PMID- 1453551 TI - Production of active and inactive renin by adrenal explant cultures and the existence of a prorenin activating enzyme in the adrenal gland. AB - We previously demonstrated high levels of inactive renin (IR) in nephrectomized rat plasma which provided evidence for extra-renal sources of IR. However, the sources of IR were unknown. This study examined whether the adrenal gland is capable of producing active renin (AR) and IR, using explants of adrenal capsules (glomerulosa portions) from control and nephrectomized (Nepex) rats. Explants from both control and Nepex rats produced large quantities of IR and small quantities of AR. The productions of both IR and AR in Nepex rats were significantly greater than in control rats. High potassium culture medium markedly increased IR and slightly, but significantly, enhanced AR in both control and Nepex rats. On the other hand, sodium had little effect on either IR or AR. A renin-angiotensin system has been reported in the adrenal gland. Recently, a prorenin activating enzyme was demonstrated in the kidney and the aortic wall. The next study was performed to demonstrate the existence of a prorenin activating enzyme in the adrenal gland, using inactive renin from culture medium from Nepex rat explants as the substrate. A 26 KD component in adrenal zona glomerulosa tissues isolated by Sephacryl S-200 column chromatography, converted IR to AR in IR rich medium. The pH optimum for prorenin activation by the enzyme was 6.5. Inhibitor studies indicate that this enzyme is a serine protease. These data suggest that (1) the adrenal gland is an extra renal source of inactive renin and (2) a prorenin activating enzyme exists in the adrenal gland. PMID- 1453552 TI - Intramolecular oscillation of the phosphorylation domain of rat cardiac sarcoplasmic reticulum titrated with arachidonoyl phosphatidylcholine. AB - Sarcoplasmic reticulum vesicles were prepared from rat myocardium. The intramolecular oscillation of the phosphorylation domain of Ca(2+)-ATPase in control vesicles and in vesicles titrated with diarachidonoyl phosphatidylcholine was studied with a nanosecond time-resolved fluorometer. The membrane viscosity of the lipid domain was decreased by the lipid titration. The phosphorylation domain was labeled with a fluorophore, anilinonaphthylmaleimide (ANM). The time course of anisotropy decay of ANM fluorescence reflects the localized oscillation in the protein structure. The half-decay time of the anisotropy was decreased by diarachidonoyl titration from 77 nsec in control vesicles to 66 nsec, suggesting an increase in the intramolecular oscillation. Concomitantly observed decreases in membrane viscosity and Ca(2+)-ATPase activity suggest that the decreased membrane viscosity destabilized the Ca(2+)-ATPase protein structure causing a reduction in Ca(2+)-ATPase activity. PMID- 1453553 TI - Dilated cardiomyopathy with recurrent intraventricular thrombosis. AB - Dilated cardiomyopathy with intraventricular thrombosis is a rare disease, most frequently encountered in adults. It rarely occurs in infants. We report here the case of a 2-year-old boy with intraventricular thrombosis due to dilated cardiomyopathy and emphasize the importance of prophylactic anticoagulant therapy in this case. PMID- 1453554 TI - High output cardiac failure caused by multiple giant cutaneous hemangiomas. AB - A 59-year-old Chinese woman had multiple giant cutaneous cavernous hemangiomas on her right upper limb which resulted in high output heart failure because they presented as a large peripheral arteriovenous (A-V) fistula. Selective right subclavian arteriography showed extremely hypertrophic arteries of the patient's right arm with a tremendous blood supply to the soft tissues; neither superselective embolization nor surgery seemed applicable to this patient. The patient's heart failure was not satisfactorily controlled by conservative treatment. PMID- 1453555 TI - Recurrent atrial flutter in apical hypertrophic cardiomyopathy. AB - Palpitations are a symptom often reported by patients with apical hypertrophic cardiomyopathy (HCM), yet the arrhythmias associated with this type of HCM have not been studied adequately. Herein, a case of persistently recurrent atrial flutter in a 63-year-old Greek man with apical HCM is presented. Synchronized direct-current shocks were used twice during his hospitalization in order to convert atrial flutter to sinus rhythm. No definite precipitating factor for the induction of atrial flutter was identified. PMID- 1453556 TI - Possible intramural site of reentrant circuit in ventricular tachycardia of nonischemic cause. Pre and intraoperative mapping studies. AB - A patient with a drug-refractory sustained ventricular tachycardia (VT) of nonischemic cause was mapped for the site of VT origin. The intraoperative mapping showed the earliest site of activation of VT on the epicardial surface at which the initial deflection of the local electrogram preceded the onset of the QRS complex of VT by 45 msec. The endocardial mapping could not indicate the site at which the electrogram was found prior to the onset of the QRS complex of VT. However, at the earliest site of the endocardial mapping, VT was entrained without change in the configuration of the QRS complex. After cessation of the rapid pacing, VT resumed at the intrinsic rate and the first post-paced return cycle was identical to each paced cycle length. The interval from the stimulus to the orthodromically captured local electrogram at the pacing site was identical to the cycle length of VT. Catheter ablation from the endocardial side and a cryoablative procedure from the epicardial side failed to eradicate the VT. These findings suggest an intramural site of VT origin and reentrant circuit of which the exit and the entrance face the epicardial and the endocardial surfaces, respectively. PMID- 1453557 TI - Proceedings of the XXVII Annual Scientific Meeting of the Society of the Spontaneously Hypertensive Rat. Hokkaido, June 28-29, 1991. Abstracts. PMID- 1453558 TI - A quadricuspid aortic valve. PMID- 1453559 TI - [Thallium-201 myocardial perfusion imaging during adenosine-induced coronary vasodilation in patients with ischemic heart disease]. AB - 201Tl myocardial perfusion imaging during adenosine infusion was performed in consecutive 55 patients with suspected coronary artery disease. Adenosine was infused intravenously at a rate of 0.14 mg/kg/min for 6 minutes and a dose of 111 MBq of 201Tl was administered in a separate vein at the end of third minute of infusion. Myocardial SPECT imaging was begun 5 minutes and 3 hours after the end of adenosine infusion. For evaluating the presence of perfusion defects, 2 short axis images at the basal and apical levels and a vertical long axis image at the mid left ventricle were used. The regions with decreased 201Tl uptake were assessed semi-quantitatively. Adenosine infusion caused a slight reduction in systolic blood pressure and an increase in heart rate. The rate pressure products increased slightly (9314 +/- 2377 vs. 10360 +/- 2148, p < 0.001). Chest pain (24%) and headache (13%) were the frequent side effects. The second-degree atrioventricular block was developed in 11 of 55 (20%) patients. All symptoms and hemodynamic changes were well tolerated and disappeared within 1 or 2 minutes after discontinuing adenosine infusion. The sensitivity and specificity for the detection of patients with coronary artery disease were 100% (31/31) and 88% (7/8), respectively. 201Tl myocardial imaging during adenosine infusion was considered to be safe and useful for evaluating the patients with ischemic heart disease. PMID- 1453560 TI - [Assessment of cardiac function and left ventricular regional wall motion by 99mTc multigated cardiac blood-pool emission computed tomography]. AB - Forty-three patients underwent the analysis of left and right ventricular (LV and RV) volumes, and LV regional wall motion by multigated cardiac blood pool single photon emission computed tomography (SPECT) with 99mTc. To calculate the cardiac volume correctly, the optimal cutoff level in relation to background level was first obtained by a phantom study. Left ventricular end-diastolic, end-systolic volume (EDV and ESV) and ejection fraction (EF) calculated thus with SPECT were correlated well with the data obtained with left ventriculography (LVG) and magnetic resonance imaging (MRI), especially using horizontal long axial image. RV stroke volume (SV) without shunt or valvular diseases was also correlated well with that of LV when it was calculated using horizontal long axial image. However, SV ratio (LVSV/RVSV) was not necessarily ideal numerical 1. In addition LV wall motion was evaluated by multicontour systolic display and phase analysis in SPECT and gated planar images. The results obtained with SPECT were better correlated with those of LVG than gated planar images. It is concluded that multigated cardiac blood pool SPECT is a clinically useful method for an evaluation of cardiac function and left ventricular regional wall motion. PMID- 1453561 TI - [Pulmonary kinetics of 13N-ammonia in smoking subjects--a quantitative study using dynamic PET]. AB - To evaluate the effect of smoking on nonrespiratory function in the lung, a dynamic PET with 13NH3 in the lung was performed in 18 normal volunteers without lung disease nor congestion (9 non-smokers, 4 exsmokers, 5 smokers). After intravenous bolus injection of 13NH3, twenty serial 5.5-second scans followed by six 30-second scans were performed. Regions of interests were assigned on the ventral, lateral and dorsal part of the right lung and time-activity curves were generated through 26 images. The activity curve demonstrated a biexponential clearance from the lung with fast and slow component. The retention fraction (RF), fractional size of the slow component, was calculated, and the half-times (t 1/2) of both components were also evaluated. A significant increase of RF and prolongation of t 1/2 of slow component were observed in smokers compared to non smokers and exsmokers. However, no significant difference of RF nor t 1/2 of both components was observed between non-smokers and exsmokers. These results suggest that long term smoking may modify the pulmonary kinetics of 13NH3, but the change is reversible after cessation of smoking for one year or longer. PMID- 1453562 TI - [Phase 2 clinical study of 99mTc-ECD--a multicenter study]. AB - A phase 2 clinical study of a newly developed brain perfusion agent, 99mTc-ECD, was performed in 166 cases of cerebrovascular diseases and impairment of brain function to evaluate effectiveness, usefulness, optimum dose and optimum timing of imaging as a multi-center study involving 10 institutions in Japan. All cases were judged as no problems on safety and any side effects due to the administration of the compound were not observed. Out of 163 cases evaluated for the clinical usefulness, valuable information for clinical diagnosis was obtained in 160 cases (98.3%), and 154 cases (94.5%) were judged as "extremely useful" or "useful". Although SPECT imaging was possible from 5 min after injection, images obtained between 60 and 90 min after injection showed relatively better image quality in many cases. Regarding standard administration dose, 400 to 800 MBq were considered to be appropriate. 99mTc-ECD is considered to be a promising radiopharmaceutical as a brain perfusion agent. PMID- 1453563 TI - [A case of meningioma with non-accumulation of 99mTc-ECD and increased accumulation of 99mTc-HMPAO in the tumor]. AB - 99mTc-ECD SPECT and 99mTc-HMPAO SPECT with or without Matas test were performed in a 62-year-old woman with meningioma in the left anterior cranial fossa. After injection of 740 MBq 99mTc-ECD or HMPAO, 64 projection images were collected with a rotating Gamma camera. Matas test was carried out by compressing the left common carotid artery for about one minute immediately after RI injection. Although 99mTc-ECD SPECT showed non-accumulation in the tumor, 99mTc-HMPAO SPECT demonstrated increased accumulation in it. This area of increased accumulation disappeared on 99mTc-HMPAO SPECT with Matas test which causes decrease in blood flow of the tumor. These findings suggest 99mTc-ECD and 99mTc-HMPAO have a different mechanisms of accumulation in the meningioma. PMID- 1453564 TI - [Clinical application of 18F-FDG-PET in patients with brain death]. AB - In order to evaluate glucose metabolism in brain death, 18F-FDG-PET scans were performed in three patients with clinically highly suspected brain death. One case was caused by head trauma and other two cases were by subarachnoid hemorrhage. All of them were in deep coma without spontaneous breathing, whose intracranial pressure was remarkably elevated up to the level of mean arterial pressure. Nineteen frames of dynamic scan were started soon after intravenous injection of 18F-FDG for one minute per frame, followed by 10 minutes of static scan which started 40 minutes after the injection. Both in dynamic and static scan, no significant intracranial accumulation of 18F-FDG was seen in all of three cases. This finding can be interpreted as the evidence that there is no significant glucose utilization from blood in the brain. This is the first report of clinical application of 18F-FDG-PET to brain death. Our results support the clinical diagnosis of brain death and 18F-FDG-PET can be of value for the assessment of glucose metabolism in patients with suspected brain death. PMID- 1453565 TI - [Clinical assessment of 99mTc-HMPAO scintigraphy in thoracic tumors]. AB - 99mTc-hexamethylpropylene amineoxime (99mTc-HMPAO) scintigraphy was performed in 15 malignant tumors in 11 patients and a patient with bronchopneumonia. A high 99mTc-HMPAO affinity for the tumors was observed on SPECT, however, the mean tumor/contralateral normal lung ratios of 99mTc-HMPAO activity (1.26) was lower than that of 201Tl-chloride (2.29). 99mTc-HMPAO uptake was seen not only in the tumors but also in the bronchopneumonia, atelectasis, and irradiated lung (containing radiation fibrosis). Moreover, a diffuse uptake in the lung was seen in a patient received repeated chemotherapy. Therefore, it is emphasized that there is a non-specific 99mTc-HMPAO uptake in those various pulmonary conditions. PMID- 1453566 TI - [Active tuberculosis in children who received INH chemoprophylaxis]. AB - Twelve children who developed active tuberculosis even after receiving isoniazid (INH) chemoprophylaxis were seen at Tokyo Metropolitan Children's Hospital from 1982 through 1991. All cases received INH more than 9 mg/kg/day, except for one case in which the amount of INH administered at the referring hospital was unknown and Streptomycin was administered together with INH. The age of starting INH prophylaxis ranged from 2 months to 13 years, and the age at which clinical symptoms and/or laboratory evidences of active tuberculosis were first manifested ranged from 4 months to 18 years. Five patients developed active tuberculosis after the completion of chemoprophylaxis and patients during chemoprophylaxis, with the first presentation ranging from primary complex (seven), chronic pulmonary tuberculosis (two), tuberculous meningitis (two), and tuberculous pleuritis (one). None of the Mycobacterium tuberculosis resistant to INH was isolated. Reviewing these patients, eleven cases had at least one of the following factors: (1) age less than two years old (2) infectious sources expectorated more Mycobacterium tuberculosis (3) delay in starting INH. Above factors should be considered in initiating INH chemoprophylaxis and subsequent follow-up of the patients. PMID- 1453567 TI - [Surgical treatment for tuberculous spondylitis; a case report]. AB - A 64-year-old woman was admitted with the chief complaints of severe back pain. Chest X-ray film on admission showed an abnormal mass lesion in the right upper mediastinum. Chest tomography and chest CT films revealed destruction of thoracic vertebrae (Th 2 and 3) and paravertebral abscess. Chemotherapy containing RFP was started under diagnosis of active tuberculous spondylitis of thoracic vertebrae. Three months later, curative operation for spondylitis were performed. She underwent the resection of necrotic bone and the anterior spinal fusion using transplanted bone autograft. Her post-operative course was good and she discharged three months after curative operation. Tuberculous spondylitis is still important diseases at the differential diagnosis from metastatic vertebral tumors. This report describes a successful case of surgical treatment for tuberculous spondylitis of thoracic vertebrae. PMID- 1453568 TI - [Counting efficacies of the CFU-enumerating method and microscopic counting method for mycobacteria located in cultured macrophages]. AB - I compared counting efficacies of CFU-enumerating method for the number of mycobacteria (Mycobacterium intracellulare and M. fortuitum) locating in cultured macrophages with that of microscopic counting method. Zymosan A-induced macrophages from ddY mice were infected with either M. intracellulare or M. fortuitum by incubation in 10% FBS-RPMI 1640 medium containing the organisms for 1 hr, thereafter thoroughly washed to remove extracellular bacilli, and cultured for 3 to 5 days. At intervals, macrophages were thoroughly rinsed and subjected to either CFU-enumeration or microscopic counting, as follows. In the former method, macrophages were lysed with 0.2% Tween 80-distilled water by sonication using Handy Sonic and CFUs were counted on 7H11 agar plates. In the latter method, the number of acid-fast bacilli was counted by microscopy for macrophages after Ziehl-Toda's staining. The number of bacteria by the CFU-enumerating method was much greater than that by the microscopic counting method. PMID- 1453569 TI - [Initial treatment of pulmonary tuberculosis with refractory factors]. PMID- 1453570 TI - [Re-treatment of refractory pulmonary tuberculosis]. PMID- 1453571 TI - [Rush cases (rapidly progressing tuberculosis) and their management]. PMID- 1453572 TI - [Evaluation of new antitubercular agents--new quinolones]. PMID- 1453573 TI - [Evaluation of new antitubercular agents--new rifamycin derivatives]. PMID- 1453574 TI - [Adoptive immunotherapy of refractory pulmonary tuberculosis using sensitized autologous lymphocytes]. PMID- 1453575 TI - [Immunotherapy of refractory pulmonary tuberculosis--IL-2 therapy]. PMID- 1453576 TI - [Surgical treatment of refractory pulmonary tuberculosis]. PMID- 1453577 TI - Modified plasma clearance technique using nonradioactive iothalamate for measuring GFR. PMID- 1453578 TI - Bradykinin-mediated effects of ACE inhibition. PMID- 1453579 TI - Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease. AB - A paucity of research data exists on the potential for early dietary modification to directly retard cystic growth and proliferation in polycystic kidney disease (PKD). We have therefore examined the relative effects of dietary protein levels and oil type on the progression of disease in a murine model of PKD. In the first study, weanling DBA/2FG-pcy (pcy) mice were fed either a normal (NP), 25%, or low (LP), 6%, casein diet with 10% of either sunflower seed oil (SO) (containing n-6 fatty acids), or fish oil (FO) (containing n-3 fatty acids), in a 2 x 2 design. At the end of the dietary treatment, kidney weight relative to body weight was higher in mice on the NP diets. In addition, kidney phospholipid to kidney weight (mumol/g) was lower in pcy mice on NP diets, indicating that the increased kidney size was largely due to increased cyst development. Replacement of dietary SO with FO resulted in alterations in renal phospholipid fatty acid compositions: 18:2 n-6, 20:4 n-6, and 22:5 n-6 were lower, and 20:5 n-3, 22:5 n-3, and 22:6 n-3 were higher in FO-fed animals. No effect of dietary lipid type on disease progression was noted, however. In a second study, morphometric analysis revealed an 11% lower percentage cyst area and a 46% lower total cyst area (mm2) in kidney sections derived from mice on LP diets compared to NP diets. These results indicate that early dietary protein restriction in PKD prior to clinical manifestation of symptoms of the disease may have a significant impact on the pathogenesis of PKD. PMID- 1453580 TI - Effect of loop diuretics on organic osmolytes and cell electrolytes in the renal outer medulla. AB - Electron microprobe analysis on freeze-dried cryosections was used to determine the effect of the loop diuretics torasemide and furosemide on intracellular electrolyte concentrations in individual cells of the outer and inner stripe of the outer medulla and on cell rubidium uptake, the latter a measure of basolateral Na-K-ATPase activity. In addition, the organic osmolytes glycerophosphorylcholine (GPC), betaine, inositol and sorbitol in cortex, outer medulla and inner medulla were measured using HPLC. Both loop diuretics significantly reduced sodium and chloride concentrations and rubidium uptake in thick ascending limb cells, but did not affect sodium concentration or rubidium uptake in the proximal straight tubule (PST) cells or in the light or dark cells of the outer medullary collecting duct (OMCD). Chloride concentrations in these cells (that is, PST cells, OMCD light and dark cells) were lowered by loop diuretics, albeit less than in thick ascending limb cells. Administration of both loop diuretics for only 20 minutes was sufficient to significantly depress tissue concentrations of GPC, betaine, and myo-inositol in the outer medulla and of GPC, betaine and sorbitol at the papillary tip. These results indicate that loop diuretics, presumably by blocking apical sodium entry, decrease thick ascending limb cellular sodium concentration and, as a consequence, reduce Na-K-ATPase activity as assessed by cell rubidium uptake. Although this has been shown previously in in vitro preparations, the present study confirms this for the first time in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453581 TI - Failure of atrial natriuretic peptide to induce natriuresis in aortocaval fistula dogs. AB - Creation of an aortocaval fistula (ACF) in dogs induces salt and water retention, activation of the renin-angiotensin and adrenergic nervous systems and renal papillary ischemia associated with high levels of circulating atrial natriuretic peptide (ANP). The effects of intrarenal ANP (1.2 micrograms/min) infusion on systemic and renal hemodynamics, renal excretory function, renal output of renin and norepinephrine (NE) and papillary plasma flow (PPF) were studied in both normal and ACF dogs. ANP did not alter systemic hemodynamics in either group, but led to a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), sodium excretion (UNaV) and fractional excretion of sodium (FENa), and a significant decrease in renal vascular resistance (RVR) and urine osmolality (UOsm) in normal dogs. GFR, RBF, RVR, V, UNaV, FENa and UOsm remained unchanged, however, in ACF dogs. In ACF dogs, both renal renin and NE output were significantly greater during baseline and remained significantly greater following ANP infusion, associated with a significantly lower PPF compared with normal dogs. These data suggest that ACF dogs are resistant to the renal effects of ANP, which can neither mitigate the hormonal mediators of sodium retention nor reverse the papillary ischemia observed in this model. PMID- 1453583 TI - Microfilament disruption occurs very early in ischemic proximal tubule cell injury. AB - Experimental ischemic acute renal failure results in disruption of proximal tubule apical membranes. Previous work utilizing immunofluorescence with an anti actin antibody has demonstrated that the apical cytoskeleton of proximal tubule cells is disrupted during ischemic injury. In this study, using rhodamine phalloidin which stains only filamentous actin, we demonstrate that graded durations of ischemia resulted in progressive disruption of proximal tubule apical microfilaments. Quantification using spectrofluorometry showed that 5, 15 and 50 minutes of ischemia resulted in 32.8 +/- 4%, 48.8 +/- 2.5%, and 58.4 +/- 2.6% decreases in apical F-actin relative to controls. Ischemia did not qualitatively affect either glomerular or distal tubule F-actin structure, though there were nonprogressive increases in glomerular fluorescence. In summary, rhodamine-phalloidin staining can be used to qualitatively and quantitatively assess proximal tubule microfilaments in vivo. We conclude that ischemia results in very early loss of proximal tubule apical microfilaments, with the majority of F-actin loss occurring within five minutes. PMID- 1453582 TI - Early glycosylation products induce glomerular hyperfiltration in normal rats. AB - The effects of early glycosylation products (Amadori Products, AP) were investigated in male Munich-Wistar rats to establish whether AP play a role in the pathogenesis of glomerular hyperfiltration of early diabetic nephropathy. To mimic such a condition, normal rats were transfused with blood containing in vitro glycated serum (Group GLYC) to achieve plasma levels of Amadori products similar to those measured in rats with streptozotocin-induced diabetes. Rats transfused with normal blood were used as control (Group CON). Glomerular hemodynamics was evaluated in basal condition (B) and during acute hyperglycemia (HG). Blood transfusion did not alter basal hemodynamics. In Group CON, HG determined a rise of single nephron GFR (41.4 +/- 3.2 vs. 32.1 +/- 1.8 nl/min, P less than 0.005), secondary to the increase of afferent effective filtration pressure (EFPa, +19% vs. B, P less than 0.01). Rats of Group GLYC, in B, had values of SNGFR higher than those of Group CON B (46.8 +/- 3 nl/min, P less than 0.05, ANOVA). This increase was mediated by a significant reduction of glomerular afferent arteriole (Ra, -38% vs. Group CON B, P less than 0.05), a rise in hydrostatic gradient pressure in glomerular capillaries (delta P, +17%, P less than 0.05) and of EFPa (+31%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453584 TI - Thromboxane in the pathogenesis of glomerular injury in diabetes. AB - The present study examined the role of thromboxane (TX) in the initiation and progression of glomerular injury in diabetic rats, as reflected by albuminuria and glomerular histology. Urinary thromboxane and albumin excretion (UTX and UAlb) were elevated by four months after induction of diabetes in the moderately hyperglycemic (200 to 400 mg/dl glucose) streptozotocin diabetic rat (SDR) compared to age-matched control rats. UTX and UAlb both increased progressively in SDR over the seven month period of study. Glomerular TX production, glomerular volume, fractional and absolute mesangial volume and glomerular basement membrane (GBM) width were also increased after seven months in SDR compared to control. Treatment of SDR with a thromboxane synthetase inhibitor (TXI) 4' (imidazol-l-yl) acetophenone (100 mg/kg/day) for seven months beginning at the time of induction of diabetes prevented the increases in UTX, UAlb, glomerular TX production, glomerular volume and mesangial volume and attenuated, but did not prevent, GBM thickening. When the same dose of the TXI was begun five months after induction of diabetes and continued for two months, UTX and ex vivo glomerular TX production were reduced by only 60% compared to untreated SDR and remained higher than corresponding values in control rats. Delayed treatment with the TXI alone did not alter UAlb compared to untreated SDR. By contrast, treatment of five month albuminuric SDR for only two months with the TXI plus the TX receptor antagonist (TXRA) Bay U3405 (5 mg/kg/day) prevented a further increase in UAlb, and reduced fractional albumin clearance and mesangial volume compared to values in untreated SDR. Combined treatment with the TXI and TXRA had no effect on GBM width or glomerular volume compared to values in untreated SDR. The results support roles for TX in the initiation of, and for TX and/or endoperoxides in the progression of glomerular injury in SDR. PMID- 1453585 TI - Peritoneal defense in continuous ambulatory versus continuous cyclic peritoneal dialysis. AB - Several centers have reported a lower rate of peritonitis among adult patients on continuous cyclic peritoneal dialysis (CCPD) as compared to those undergoing continuous ambulatory peritoneal dialysis (CAPD). Preliminary results of our ongoing prospective randomized study comparing CAPD-Y with CCPD also suggest a lower peritonitis incidence among CCPD-treated patients. To investigate whether the two dialysis regimens could result in differences in local host defense, we studied peritoneal macrophage (PMO) function and effluent opsonic activity in eight patients established on CAPD-Y matched with eight chronic CCPD patients. Since short and long dwell times are inherent to both dialysis modalities, and we previously found that dwell time has an impact on PMO function and effluent opsonic activity, patients were studied after both a short (4 hr) and a long (15 hr) dwell time. In both groups PMO phagocytic capacity increased significantly with dwell time (39 +/- 3.3% at 4 hr vs. 58 +/- 4.2% at 15 hr in CAPD patients, and 40 +/- 3.9 vs. 72 +/- 3.3% in CCPD patients; P less than 0.01), as did PMO peak chemiluminescence response (31 +/- 4.9 vs. 77 +/- 7.2 counts.min-1/10(4) cells in CAPD, and 22 +/- 3.9 vs. 109 +/- 21.2 counts.min-1/10(4) cells in CCPD; P less than 0.01) and effluent opsonic activity (41 +/- 7.6 vs. 73 +/- 5.8% in CAPD and 39 +/- 6.2 vs. 70 +/- 5.9% in CCPD; P less than 0.01). However, no significant difference was found in either variable between CAPD and CCPD patients when dwell times were equal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453586 TI - Interleukin-8 and polymorphoneutrophil leucocyte activation in hemolytic uremic syndrome of childhood. AB - Polymorphoneutrophil leucocytes (PMNLs) are implicated in the pathogenesis of diarrhea-associated hemolytic uremic syndrome (D+ HUS). We investigated mechanisms of PMNL involvement by measuring tumor necrosis factor alpha (TNF alpha) and the novel cytokine, interleukin-8 (IL-8), a potent activator of neutrophils, together with alpha 1- antitrypsin-complexed elastase (alpha 1-AT-E) as a marker of neutrophil degranulation, and anti-neutrophil cytoplasmic antibodies (ANCA). IL-8 was not detected in the 17 normal children, but was significantly elevated in 20 of 25 D+ HUS children (P less than 0.005), and in three of nine children with non-diarrhea-associated (D-) HUS. Sequential data showed that IL-8 peaked transiently in the circulation, reaching a maximum just before a more protracted burst of alpha 1-AT-E. The IL-8 levels correlated significantly with circulating alpha 1-AT-E concentrations (r = 0.50, P less than 0.05). In D+ HUS IL-8 levels also correlated with the PMNL count (r = 0.63, P less than 0.005), and the highest values were seen in those children who died in the acute phase of the disease. TNF alpha was raised in only 1 of 16 D+ HUS children and in no patients were ANCA detected. The data suggest that PMNLs in HUS are recruited by IL-8, that this cytokine plays a key role in the PMNL activation which occurs, and that agents which suppress this recruitment and activation might play a therapeutic role in this disorder. PMID- 1453587 TI - Renal handling of silicon in normals and patients with renal insufficiency. AB - We have compared the renal handling of silicon in 16 patients with renal insufficiency to 14 normal individuals. Silicon, phosphate and creatinine were measured in plasma and urine samples. The renal insufficiency group showed significant increases in plasma silicon (1.28 +/- 0.19 vs. 0.17 +/- 0.03 mg/liter), creatinine (5.19 +/- 0.85 vs. 0.89 +/- 0.03 mg/dl) and phosphate (1.33 +2- 0.11 vs. 1.07 +/- 0.4 mmol/liter). Fractional phosphate excretion was increased in the renal insufficiency group (0.55 +/- 0.07 vs. 0.14 +/- 0.01). In contrast, the fractional excretion of ultrafiltrable silicon was not significantly different between groups (0.78 +/- 0.07 vs. 0.87 +/- 0.06). It is concluded that renal insufficiency does not alter the tubular handling of silicon and that regulatory control of silicon excretion is unlikely. PMID- 1453588 TI - Predicting chronic renal insufficiency in idiopathic membranous glomerulonephritis. AB - We developed an approach in quantifying the risk of developing chronic renal insufficiency (CRI) based on a cohort of 184 patients with idiopathic membranous glomerulonephritis (IMGN), prospectively followed by the Toronto Glomerulonephritis Registry between 1974 and 1988. After a mean follow-up period of 5.8 years, 26% of patients developed CRI (defined as persistent reduction of creatinine clearance (CCr) less than or equal to 60 ml/min/1.73 m2 for greater than or equal to 12 months). We found that when compared to the baseline probability of the unselected patients, the severity of proteinuria at kidney biopsy added only marginally to the prediction of CRI. We introduced a special test condition: persistent proteinuria (PP) (that is, duration of proteinuria, g/day, above different cut-off levels). We examined the positive predictive value (PPV) and sensitivity (SEN) of 15 arbitrarily chosen levels of PP (that is, proteinuria greater than or equal to 4, 6 or 8 g/day persisting for greater than or equal to 6, 9, 12, 18 or 24 months) to select levels with optimal predictive characteristics. We found that PP greater than or equal to 8 g/day for greater than or equal to six months was a simple and useful predictor of CRI with a PPV and SEN of 66%. To further improve our prediction, we tested the following parameters: age, sex, initial SCr and CCr, proteinuria, serum albumin, hypertension, rate of change of CCr over time, and therapy (steroids +/- immunosuppressive drugs) in a multivariate analysis. Proteinuria, initial CCr, and rate of change of CCr were most important in predicting CRI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453589 TI - Risk of peritonitis and technique failure by CAPD connection technique: a national study. AB - Peritonitis has been a leading complication of long-term therapy with continuous ambulatory peritoneal dialysis (CAPD). This study was designed to evaluate the risk of peritonitis and technique failure according to the initial CAPD connection technique. Patients from all U.S. facilities starting CAPD therapy at home between January 1 and June 30, 1989 were followed for up to 21 months on the initial CAPD connection technique to change in technique or dialytic modality, to transplantation, death or loss to follow-up. Patients were grouped into standard connection techniques (SCT) (N = 1,133), Y-set (N = 1,067), standard UV set (N = 916) and O-set (N = 167). The time to first peritonitis episode was analyzed actuarially and by using the Cox proportional hazards model which adjusted for age, sex, race, cause of ESRD, CAPD program size and ESRD therapy prior to CAPD. Peritonitis occurred on average at 9.0 month intervals with SCT, 15.0 months with Y-set, 13.4 with standard UV and 9.4 with O-set. The relative risk (RR by Cox analysis) of first peritonitis compared to SCT was 0.60 (40% lower) for the Y-set (P less than 0.01), 0.75 for standard UV (P less than 0.01), and similar to SCT (RR = 0.96) for the O-set (NS), all else being equal. Analysis time to second (N = 1,271) peritonitis episode gave similar results as did analysis of time to CAPD technique failure. Significantly higher RR of peritonitis and technique failure was observed for younger and black patients. These findings suggest the utilization of connection techniques with superior results. PMID- 1453590 TI - Effects of oxygen breathing and erythropoietin on hypoxic vasodilation in uremic anemia. AB - Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, 8 males) before and after correction of anemia with rHuEPO, 50 U/kg 3x/week (Hb: 7.4 +/- 0.3 vs. 10.8 +2- 0.3 g/dl, P less than 0.0001). Hypertension (greater than 15 mm Hg rise in mean BP) occurred in 11 patients. The study was performed while breathing room air and repeated after breathing 60% O2 for 10 to 12 minutes. Before rHuEPO therapy, total blood O2 content increased from 10.01 +/- 0.39 to 10.32 +/- 0.29 ml O2/100 ml blood with breathing 60% O2 (P less than 0.01). After correction of anemia it was 14.65 +/- 0.40 ml O2/100 ml blood on room air (P less than 0.001). There was a significant decrease in forearm blood flow (7.9 +/- 0.5 vs. 6.5 +/- 0.6 ml/min/100 ml tissue, P less than 0.05) and increase in forearm vascular resistance (12.8 +/- 0.1 vs. 16.8 +/- 0.2 mm Hg/ml/min/100 ml tissue, P less than 0.05) with O2 breathing prior to rHuEPO therapy in the blood pressure responders, but no change in these parameters in the group in which blood pressure remained unchanged. When all patients were studied on room air, forearm vascular resistance rose significantly after correction of anemia (13.0 +/- 0.8 vs. 16.3 +/- 0.8 mm Hg/ml/min/100 ml tissue, P less than 0.05), compared with that prior to rHuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453591 TI - Methylprednisolone dosage effects on peripheral lymphocyte subpopulations and eicosanoid synthesis. AB - Glucocorticoids have a major role in the treatment of glomerular diseases. Despite recent advances in understanding of their mechanism of action, very few studies have addressed the relative advantage of the wide range of different dose regimens employed in clinical practice. We studied the effects of methylprednisolone given intravenously for three consecutive days at the doses of 1 mg/kg (group 1, N = 7; group 2, N = 5), 5 mg/kg (group 3, N = 5) or 15 mg/kg (group 4, N = 6) on total blood peripheral leukocytes and on lymphocyte subsets in patients with glomerular diseases, and investigated whether such effects were a function of the drug concentration in the blood. Since glucocorticoids have an inhibitory effect on the formation of eicosanoids in different cells, we also investigated in the same patients the effect of 1 and 15 mg/kg methylprednisolone on systemic and renal eicosanoid synthesis. Results of pharmacokinetic study showed that the three different doses of methylprednisolone we used resulted in major differences in patient's exposure to the drug, and within the same dose there was a great individual variability. By contrast the three different doses of methylprednisolone induced a comparable drop in the absolute number of lymphocytes six hours after the first injection of methylprednisolone, while 24 hours later blood lymphocyte counts returned to the pre-injection values in all patients. Analysis of lymphocyte subsets showed a selective decrease in the number of circulating CD4+ and CD8+ cells six hours after methylprednisolone which was comparable in the four groups of patients studied. As for the effect of methylprednisolone on systemic and renal eicosanoid synthesis in patients with glomerular diseases, 1 and 15 mg/kg were equally unable to reduce thromboxane A2 (TxA2) and prostaglandin E2 (PGE2) release by circulating polimorphonuclear cells (PMNs). By contrast, methylprednisolone partially inhibited eicosanoid synthesis by PMNs in vitro. Consistent with the data on PMNs, urinary excretion of TxA2 and prostacyclin (PGI2) metabolites were unaltered by the different doses of methylprednisolone. By contrast urinary PGE2 was markedly and significantly reduced in patients given 15 but not 1 mg/kg. We conclude that 1 mg/kg methylprednisolone given to patients with glomerular diseases has the same effect on peripheral total blood leukocyte count and lymphocyte subsets than 5 and 15 mg/kg. The same is true for eicosanoid synthesis by PMNs. Renal synthesis of PGE2 is inhibited by 15 mg/kg but not by 1 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1453592 TI - Using USRDS generated mortality tables to compare local ESRD mortality rates to national rates. AB - Mortality tables of the U.S. Renal Data System allow description of national mortality rates among prevalent dialysis patients in five-year age groups and four major categories of causes of ESRD for Black and White patients. Based on these tables derived from over 50,000 deaths in dialysis patients during 1987 to 1989 a methodology is described that allows comparison of local or regional mortality rates to national rates with determination of a standardized mortality ratio and statistical significance. Since this methodology adjusts for patient age, race and cause of ESRD, it can serve as a useful tool for dialysis research and local quality assurance. PMID- 1453593 TI - The nature of clinical trials in nephrology. PMID- 1453594 TI - Sodium-dependent phosphate transport in a rat kidney endosomal fraction. AB - An endosome-enriched fraction was prepared from rat kidney cortex by a standard procedure employing centrifugation on a Percoll gradient. This fraction showed time-dependent accumulation of inorganic phosphate (Pi) which was stimulated two- to threefold during the initial phase by an inwardly directed Na+ gradient. Na+ gradient-dependent Pi accumulation decreased with increasing medium osmolality and Pi binding accounted for only 16% of the total accumulation at two minutes. Like the Pi transporter in the brush border membrane (BBM), the Na+ gradient dependent Pi uptake (but not the Na(+)-independent component) by the endosomal fraction was stimulated by intravesicular Pi and by an outwardly directed proton gradient, and was inhibited by extravesicular arsenate. Unlike the Pi transporter in BBM, the endosomal Pi transporter was not changed by acidic pH under non gradient conditions. Activation of the endosomal proton pump by extravesicular ATP, leading to acidification of the vesicle interior, was accompanied by stimulation of endosomal Na+ gradient-dependent Pi transport. Inhibition of the proton pump by deletion of chloride or addition of N-ethylmaleimide abolished the stimulation of Pi uptake by ATP. The data indicate that the Na(+)-dependent Pi transporter in renal endosomal fractions is an intrinsic endosomal component. It remains to be determined if the endosomal Pi transporter plays a role in regulation of renal Pi transport. PMID- 1453595 TI - Reduced capillary density in the myocardium of uremic rats--a stereological study. AB - Using stereological techniques capillaries, interstitium and myocardial fibers were analyzed in perfusion-fixed hearts of subtotally nephrectomized male Sprague Dawley rats with uremia of 14 months duration (or their sham-operated controls). Uremic rats had higher systolic blood pressure (140 +/- 20.3 mm Hg vs. 119 +/- 6.61 mm Hg) and left ventricular weight/body weight ratio (3.37 +/- 0.09 mg/kg vs. 2.01 +/- 0.12 mg/kg) than controls, and had slight anemia (Hct 35.0 +/- 3.16% vs. 40.4 +/- 3.3%). Length density (Lv) of capillaries, that is, capillary length per unit myocardial volume, was significantly (P < 0.001) decreased in uremia (2485 +/- 264 mm/mm3 vs. 3329 +/- 194 mm/mm3) versus controls. In parallel, surface density and volume density of the capillary lumina were also reduced (7.95 +/- 1.69 cm3/cm3 vs. 11.4 +/- 1.8 cm3/cm3) in the uremic rats. We conclude that in experimental uremia, cardiac hypertrophy is not accompanied by a commensurate increase in capillaries. PMID- 1453596 TI - Insulin-responsive glucose transporter expression in renal microvessels and glomeruli. AB - The insulin-responsive glucose transporter (GLUT4) is expressed at high levels in fat and skeletal muscle, which account for the majority of insulin-stimulated glucose uptake. However, GLUT4 is also expressed at lower levels in kidney and several other tissues. We have used a variety of protein and mRNA detection techniques to determine the sites of renal GLUT4 expression. Indirect immunofluorescence experiments with two specific anti-peptide antisera detected GLUT4 in the smooth muscle cells of the rat renal microvasculature, in renal glomerulus, and in cultured glomerular mesangial and epithelial cells. PCR amplification of cDNA derived from microdissected renal glomeruli, microvessels and tubules corroborated this distribution of GLUT4, and Northern blotting demonstrated GLUT4 mRNA in cultured glomerular mesangial cells. Both the immunofluorescence and PCR data suggested that GLUT4 is most highly expressed in renal microvessels. Our results show that certain renal cells, such as renal microvascular smooth muscle cells, express the insulin-responsive glucose transporter and therefore may demonstrate altered glucose uptake and metabolism in diabetes mellitus. PMID- 1453597 TI - IGF-I binding and IGF-I mRNA expression in the post-ischemic regenerating rat kidney. AB - The localization of IGF-I peptide and IGF-I mRNA was investigated in the post ischemic regenerating rat kidney using immunohistochemistry and non-radioactive in situ hybridization techniques. In addition, the distribution and relative quantity of IGF-I binding sites were studied by autoradiographic ligand-binding techniques. Two and three days after the injury, morphological signs of an intense regenerative activity was evident. By this time a substantial number of the regenerating cells were stained with a monoclonal antibody against the M1 subunit of ribonucleotide reductase, a proliferative marker used. Low proliferative tubular cells, replacing those that had been injured, were seen lining the tubular basement membrane. By seven days, the morphology in the cortex was quite normalized, while cells of the S3 segments in the outer medulla remained dedifferentiated. The regenerative cells expressed IGF-I peptide and IGF I mRNA in a transient manner and this was found to correlate better to cell differentiation than cell division. In addition, non-tubular cells, predominantly macrophages, expressed both the IGF-I peptide and the mRNA. The IGF-I binding was significantly increased in the regenerative zone at all times studied and began to decline at day seven. The binding characteristics were found to be compatible with binding to the IGF-I receptor. Altogether, these findings provide circumstantial evidence that IGF-I is of trophic importance in the regeneration of renal tubular cells. The data are compatible with a local production and action of IGF-I, suggesting an autocrine and/or paracrine mode of action during the regenerative process. PMID- 1453598 TI - Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor. AB - We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453599 TI - Hypoxia-mediated impaired differentiation by LLC-PK1 cells: evidence based on the protein kinase C profile. AB - We recently reported that mild hypoxia in LLC-PK1 cells, grown in standard fashion under a still layer of overlying medium at 5% CO2/18% O2 environment, result in decreased oxidative metabolism and impaired differentiated functions in comparison to adequately oxygenated cultures maintained either under a higher oxygen (36% O2) environment or conditions of continuous rocking of the media fluid. In the present study, subcellular distribution of a regulatory enzyme protein kinase C (PKC) was examined between hypoxic still and normoxic rocked LLC PK1 cells. Subconfluent cultures of hypoxic LLC-PK1 cells exhibited significantly lower and predominantly membrane-bound PKC activity in comparison to mostly cytosolic localization of this enzyme in normoxic rocked cells. One hour of exposure of adequately oxygenated-rocked LLC-PK1 cells with the phorbol ester TPA, a dedifferentiating agent that did not effect the cell ATP content, resulted in significant inhibition of dome formation and sodium-dependent glucose transport activity, a partial loss of pH-responsive ammoniagenesis, and almost complete translocation of protein kinase C activity from cytosol to the membrane pool; all of which resembles the behavior of hypoxic still cultured cells. In addition, acute re-oxygenation of hypoxic still cultures by rocking the media fluid for one hour resulted in an increase in cell ATP content to the cellular levels of ATP observed in normoxic rocked cells. However, all the parameters of differentiation were unaffected by re-oxygenation. These studies support the notion that hypoxia can act in some primary fashion, independent of its effects on energy metabolism, to impair cellular differentiation in LLC-PK1 cells. They also raise the possibility that activation of protein kinase C may act as an important mediator in this process. PMID- 1453600 TI - Urodilatin, not nitroprusside, combined with dopamine reverses ischemic acute renal failure. AB - The present study was undertaken to: (a) clarify the comparative renal potency of bolus injection of the natriuretic peptides urodilatin and ANF99-126 in the rat; (b) establish whether or not intravenous (i.v.) infusion of urodilatin (200 ng/min) combined with dopamine (UD) to maintain mean arterial pressure could improve GFR or renal histology in established experimental ischemic acute renal failure (ARF) induced by 30 minutes of bilateral renal artery clamping; (c) assess comparative efficacies of nitroprusside, an activator of soluble guanylate cyclase, combined with dopamine (ND) or control infusions of dopamine alone (DA), under equivalent conditions; and (d) determine effects of intra-renal arterial infusions of the stable cGMP analogue dibutyryl-cGMP immediately after renal artery clamping (RAC). After initial dose finding studies, i.v. infusion of UD 24 hours after 30 minutes of RAC improved GFR over five hours from 0.24 +/- 0.04 to 1.0 +/- 0.16 ml/min in association with a threefold rise in plasma cGMP and a 13 fold increase in urinary cGMP excretion. Plasma creatinine dropped by 41% from 230 +/- 16 to 135 +/- 18 microM/liter and was still reduced 24 hours later with values averaging 106 +/- 14 compared to 274 +/- 53 microM/liter in non-treated animals. During infusion, UV and FENa+ increased from 1.4 +/- 0.2 to 8.3 ml/min, and from 2.9 +/- 0.5 to maximum values of 15.8 +/- 2.4%. ND or DA alone were less effective, increasing GFR only to 14 and 20%, respectively, of normal values, but improvements were not sustained; in contrast to UD, ND did not alter plasma or urinary cGMP. In addition, DBcGMP was ineffective in improving GFR during early ARF. Histologically UD, but not ND, markedly reduced the incidence of granular casts, tubular desquamation and tubular necrosis in cortical areas and increased the incidence of medullary mitoses. PMID- 1453602 TI - Alport syndrome and diffuse leiomyomatosis: deletions in the 5' end of the COL4A5 collagen gene. AB - Alport syndrome (AS) is an hereditary glomerulonephritis that is mainly inherited as a dominant X-linked trait. Structural abnormalities in the type IV collagen alpha 5 chain gene (COL4A5), which maps to Xq22, have recently been detected in several patients with AS. The association of AS with diffuse esophageal leiomyomatosis (DL) has been reported in 24 patients, most of them also suffering from congenital cataract. The mode of transmission and the location of the gene(s) involved in this association have not been elucidated. Southern blotting using cDNA probes spanning the whole COL4A5 and a 5' end COL4A5 genomic probe showed that three out of three patients with the DL-AS association had a deletion in the 5' part of the COL4A5 gene extending beyond its 5' end. This indicates that the same gene, COL4A5, is involved in classical AS and in DL-AS and that the transmission of DL-AS is X-linked dominant. These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS. PMID- 1453601 TI - Glomerular hemodynamic alterations during acute hyperinsulinemia in normal and diabetic rats. AB - Treatment of insulin dependent diabetes invariably requires exogenous insulin to control blood glucose. Insulin treatment, independent of other factors associated with insulin dependent diabetes, may induce changes that affect glomerular function. Due to exogenous delivery of insulin in insulin dependent diabetes entering systemic circulation prior to the portal vein, plasma levels of insulin are often in excess of that observed in non-diabetics. The specific effects of hyperinsulinemia on glomerular hemodynamics have not been previously examined. Micropuncture studies were performed in control (non-diabetic), untreated diabetic and insulin-treated diabetic rats 7 to 10 days after administration of 65 mg/kg body weight streptozotocin. After the first period micropuncture measurements were obtained, 5 U of regular insulin (Humulin-R) was infused i.v., and glucose clamped at euglycemic values (80 to 120 mg/dl). Blood glucose concentration in non-diabetic controls was 99 +/- 6 mg/dl. In control rats, insulin infusion and glucose clamp increased nephron filtration rate due to decreases in both afferent and efferent arteriolar resistance (afferent greater than efferent) resulting in increased plasma flow and increased glomerular hydrostatic pressure gradient. However, insulin infusion and glucose clamp produced the opposite effect in both untreated and insulin-treated diabetic rats with afferent arteriolar vasoconstriction resulting in decreases in plasma flow, glomerular hydrostatic pressure gradient and nephron filtration rate. Thromboxane A2 (TX) synthetase inhibition partially decreased the vasoconstrictive response due to acute insulin infusion in diabetic rats preventing the decrease in nephron filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453604 TI - On the probability that kidneys are different in autosomal dominant polycystic disease. AB - We hypothesized that highly variable cyst fluid sodium concentrations are a characteristic of every kidney in autosomal dominant polycystic kidney disease (ADPKD). We added our data on sodium concentrations in 124 fluids from ten ADPKD kidneys to data published by others of concentrations in 32 fluids from five kidneys. The values ranged from 3 to 207 mEq/liter; none fell between 59 and 74 mEq/liter. Fluids were designated as low (< 60 mEq/liter; 50 fluids) or high (> 60 mEq/liter; 106 fluids) sodium fluids. Transmission electron microscopy identified differences in the depths of apical tight junctions between cells from cyst walls of 12 of the low and 10 of the high sodium fluids from two kidneys (mean +/- SE depths of 2039 +/- 74 A vs. 386 +/- 18 A respectively; P < 0.0001). When fluids were grouped by kidney of origin, six of the 15 kidneys had only high sodium fluids. The probability that chance had led to the sampling of only high sodium fluids in these organs, given that 32% of all fluids were low sodium fluids, was calculated at < 0.00015. The possibility must be considered that all kidneys are not alike in ADPKD. PMID- 1453603 TI - Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients. Italian Group for the Study of Intravenous Calcitriol. AB - Intravenous calcitriol is known to directly suppress PTH secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum PTH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 +/- 0.02 (SEM) micrograms (0.015 micrograms/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calcium-phosphate products exceeded 60.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453605 TI - Influence of the level of hydration on the renal response to a protein meal. AB - Recent studies have suggested that the renal effects of high protein intake could be mediated, at least in part, by vasopressin and/or an increase in the urinary concentrating activity. The present study investigated the influence of the level of hydration, and hence of the activity of the concentrating process, on the renal response to an acute oral protein load. Clearance studies were performed before (Control) and during three hours after a protein meal (1.5 g/kg body wt protein as cooked meat) in ten healthy volunteers. This study was performed twice at a two to three week interval under either constant low (LowH) or high (HighH) hydration. In spite of the marked difference in initial diuresis (3.1 +/- 0.3 in LowH vs. 13.9 +/- 0.7 ml/min in HighH) and urine osmolality (501 +/- 42 in LowH vs. 99 +/- 3 mOsm/kg H2O in HighH), a similar relative decrease in urine flow rate was observed following the meal in both conditions. TcH2O increased progressively by 70% in LowH whereas CH2O decreased by 40% in HighH. Plasma vasopressin showed a progressive increase with time in LowH (from 1.10 +/- 0.26 in control, to 1.98 +/- 0.35 pg/ml at the third hour after the PM, P < 0.05) but not in HighH (0.53 +/- 0.09 to 0.70 +/- 0.17 pg/ml). Glomerular filtration rate (inulin clearance) increased significantly on the second post-prandial hour under LowH but not under HighH. Excretions rates of Na, Cl, K, and urea increased after the meal, however, not to the same extent nor with the same time course in the two conditions. Significant positive correlations were observed between GFR and TcH2O, urine osmolality, or the ratio of urine-to-plasma urea concentrations in LowH. These results suggest that the protein-induced hyperfiltration is partially blunted by a high water intake, and hence is dependent, directly or indirectly, on the urine concentrating activity. PMID- 1453606 TI - Ketodiet, physiological calcium intake and native vitamin D improve renal osteodystrophy. AB - The effects of a very low-protein diet (VLPD) supplemented with amino acids and ketoanalogues (KA) and with 1 g of calcium carbonate and 1000 IU of vitamin D2, were studied in 17 patients with advanced renal failure (GFR < or = 20 ml/min) over a period of one year. The protein intake was 0.3 g protein/kg body wt/day. Daily phosphorus and calcium intake were respectively 1,500 mg and 300 mg. Sequential bone densitometry was performed and bone histomorphometry after double tetracycline labeling was evaluated, before and after one year of diet. Calcium and phosphate metabolism parameters were monitored every two months. In spite of a significant decrease of GFR, phosphorus, parathyroid hormone (1-84) and osteocalcin plasma levels decreased significantly, while low plasma bicarbonate normalized, and calcitriol and calcium levels remained respectively low and normal. Before the diet, histological study disclosed four cases of mixed osteopathy: osteomalacia associated with osteitis fibrosa (OM/OF), nine pure osteitis fibrosa (OF) and four with normal bone remodeling (NB). After one year of diet, the OM component of OM/OF disappeared, as evidenced by a normalization of the mineral apposition rate and osteoid thickness. In the patients presenting pure OF, a significant decrease in osteoblastic and osteoclastic surfaces, in the number of osteoclasts, and in the bone formation rate (BFR) were found. Vertebral mineral density measured by quantitative computerized tomodensitometry did not change significantly. In conclusion, this study not only confirms the beneficial effects of VLPD + KA + calcium on uremic hyperparathyroid bone disease in advanced renal failure assessed using static bone histomorphometry, but also shows a correction of histodynamic bone parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453607 TI - Renal function 17 to 23 years after chelation therapy for childhood plumbism. AB - An elegant retrospective description of an epidemic of chronic renal failure occurring in patients with histories of untreated childhood lead poisoning in Queensland, Australia established beyond reasonable doubt the existence of lead nephropathy. However, a retrospective uncontrolled report from Boston in 1963 refuted the claim that there are serious renal consequences of untreated childhood lead poisoning. We conducted a controlled prospective, longitudinal study to examine the effects of childhood lead poisoning on renal function 17 to 23 years after chelation therapy. The present study reports the results of renal functional tests in a unique cohort of study subjects (N = 62) with significant lead poisoning (initial PbB > 100 micrograms/dl) diagnosed and treated between 1966 and 1972 and their age-matched control siblings (N = 19; initial PbB < 40 micrograms/dl). During the past nine years serial determinations of renal function on all study subjects and control siblings were obtained. Mean values of systolic and diastolic blood pressures, serum creatinine, serum beta 2 microglobulin, fractional excretion beta 2-microglobulin, urinary protein:creatinine ratio, serum phosphate, tubular reabsorption of phosphate, serum uric acid, and urinary specific gravity were similar in study subjects compared with sibling controls. The frequency of abnormal values for these tests was similar in the two groups. Multiple linear regression analyses failed to demonstrate a significant influence of the presence of plumbism or initial PbB on serum creatinine or systolic or diastolic blood pressure. A modest increase in serum creatinine values was observed over a nine year period in four of 62 study subjects (1.4, 1.4, 1.5, 1.6 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453608 TI - Anaphylactoid reactions associated with reuse of hollow-fiber hemodialyzers and ACE inhibitors. AB - From July 18 through November 27, 1989, 12 anaphylactoid reactions (ARs) occurred in 10 patients at a hemodialysis center in Virginia. One patient required hospitalization; no patients died. ARs occurred within minutes of initiating dialysis and were characterized by peripheral numbness and tingling, laryngeal edema or angioedema, facial or generalized sensation of warmth, and/or nausea or vomiting. All 12 ARs occurred with dialyzers that had been reprocessed with an automated reprocessing system. A cohort study, including all patients undergoing dialysis sessions on the six days when an AR occurred, showed that the patients who experienced ARs were significantly more likely than patients who did not to be treated with angiotensin-converting enzyme (ACE) inhibitors (7/10 vs. 3/33; relative risk = 7.9; 95% confidence interval = 2.5 to 25.2) and to have been exposed to reused dialyzers rather than to new dialyzers (12/70 sessions vs. 0/31; P = 0.016). In those sessions using a reused dialyzer, the mean number of dialyzer uses in case-sessions was significantly higher than for noncase-sessions (10.3 vs. 6.2; P = 0.016). After reuse of dialyzers was discontinued at the center, no further ARs occurred, despite the continued administration of ACE inhibitors. This is the first report of an outbreak of ARs associated exclusively with reused dialyzers. We hypothesize that interactions between a dialyzer that has been repeatedly reprocessed and reused, blood, and additional factors, such as ACE inhibitors, increased the risk of developing ARs. PMID- 1453609 TI - Decreased low-density lipoprotein receptor function and mRNA levels in lymphocytes from uremic patients. AB - The mechanisms by which renal failure causes hyperlipoproteinemia remain unclear. To investigate the potential role of the low-density lipoprotein (LDL) receptor in lipoprotein metabolism in uremia we measured LDL receptor function in peripheral blood mononuclear cells (PBMC) from uremic patients and control subjects using a functional assay in which proliferation of lectin-stimulated PBMC in the presence of lovastatin was dependent upon internalization of exogenous cholesterol via a functional LDL receptor. The amount of LDL required to reverse 50% of lovastatin-induced inhibition of proliferation in PBMC from uremic patients was significantly greater (3.6 +/- 1.8 micrograms/ml, N = 33, P < 0.05) than controls, (1.99 +/- 0.6 micrograms/ml, N = 37). Abnormal LDL receptor function in four uremic patients normalized following renal transplantation. To investigate the molecular basis for LDL receptor dysfunction, we directly quantitated LDL receptor messenger RNA (mRNA) in PBMC from uremic patients and control subjects using a ribonuclease protection assay. LDL receptor mRNA expression in uremic patients was 0.42 +/- 0.08 (N = 10), significantly lower (P < 0.015) than in normal subjects, 0.71 +/- 0.08 (N = 14). These data suggest that an acquired defect in LDL receptor function in PBMC from uremic patients exists which may be due to decreased LDL receptor expression. These abnormalities, if present in other tissues, could contribute to the aberrant lipoprotein metabolism which is a consistent feature of uremia. PMID- 1453610 TI - Severe defect in clearing postprandial chylomicron remnants in dialysis patients. AB - Lipid abnormalities have been suggested as a major cause of the accelerated atherosclerosis and the high incidence of coronary heart disease in chronic renal failure patients. In the present work the postprandial lipoprotein metabolism was studied in chronic dialysis patients with or without fasting hypertriglyceridemia using the vitamin A loading test. This method investigates specifically postprandial lipoprotein metabolism. The determination of vitamin A ester level retinyl palmitate (RP) differentiates the circulating plasma chylomicron and chylomicron remnant fractions from the endogenous VLDL and IDL. Subjects with normal renal function with or without fasting hypertriglyceridemia served as control groups. Dialysis patients have significantly higher level of chylomicron remnants for a more prolonged period of time than controls, irrespective of their fasting triglyceride levels. The area below retinyl palmitate chylomicron remnants curve was 26308 +/- 12422 micrograms/liter.hr in the normolipidemic dialysis patients, significantly higher than (6393 +/- 2098 micrograms/liter.hr; P < 0.0001) in the normolipidemic controls. The retinyl palmitate chylomicron remnants curve of the hypertriglyceridemic dialysis patients was 21021 +/- 4560 micrograms/liter.hr, which was higher than 12969 +/- 2215 micrograms/liter.hr (P < 0.0001) in the hypertriglyceridemic controls. Moreover, the hypertriglyceridemic dialysis patients had an additional defect in the lipolysis metabolic step, that is, accumulation of chylomicrons in circulation. These findings show a severe defect in postprandial lipoprotein metabolism in chronic renal failure patients. The prolonged exposure of the vascular wall to high chylomicron remnant concentrations might be an important pathogenetic factor in the accelerated atherosclerosis seen in chronic dialysis patients. PMID- 1453611 TI - IgA nephropathy in patients with congenital C9 deficiency. AB - The clinical, histologic, and immunopathological findings of three young Japanese males with congenital C9 deficiency and primary IgA nephropathy are reported. The C9 deficiency was discovered either through mass complement screening, or when low hemolytic activity for CH50 and normal C3 levels were detected in plasma. Hematuria and proteinuria were detected at the age of 8 or 9 years as a result of annual urinary screening tests for school children. Renal biopsy showed focal and segmental mesangial proliferation with small epithelial crescents in one patient, and mild, diffuse mesangial proliferation in two. IgA and C3 were deposited predominantly in the mesangial area, and staining for C9 was negative in these patients. Electron microscopy revealed electron dense deposits predominantly in mesangial and paramesangial zones. Immunohistochemical staining in renal biopsy tissues from two patients showed mesangial staining for C5, C8, and S-protein, but staining for C5b-9 neoantigen was completely negative. These results show that the formation of C5b-9 complex is not essential for the induction of human IgA nephropathy, and also for the proliferation of mesangial and even parietal epithelial cells. PMID- 1453612 TI - Renal histology in polycystic kidney disease with incipient and advanced renal failure. AB - Renal specimens were obtained at surgery or postmortem from patients with autosomal dominant polycystic kidney disease (ADPKD). Patients had either serum creatinine (SCr) below 350 mumol/liter (N = 12) or terminal renal failure (N = 50). Specimens were examined by two independent observers using a carefully validated score system. Mean glomerular diameters were similar in ADPKD patients with early renal failure (176 +/- 38 microns) and in victims of traffic accidents (177 +/- 23 microns), while they were significantly greater in diabetics with comparable renal function (205 +/- 16 microns). Glomerular diameters in ADPKD patients with terminal renal failure (191 +/- 45 microns) and with early renal failure were not significantly different. On average, 29% of glomeruli (17 to 62) were globally sclerosed in early renal failure, and 49% (19 to 93) in terminal renal failure. The proportion of glomeruli with segmental sclerosis was less than 4% in both groups. Marked vascular sclerosis, interstitial fibrosis, and tubular atrophy were present in early renal failure, and even more so in terminal renal failure. Interstitial infiltrates were scarce and consisted mainly of CD4 positive lymphocytes and CD68 positive macrophages. Immunestaining with monoclonal renin antibodies showed an increased juxtaglomerular index and expression of renin by arterioles adjacent to cysts, as well as by cyst wall epithelia. The data show more severe vascular and interstitial, but not glomerular, changes in ADPKD with advanced as compared to early renal failure. PMID- 1453613 TI - Glucose homeostasis and the kidney. PMID- 1453614 TI - [Surgical treatment of congenital aneurysm of the internal jugular vein in children]. AB - In the pathogenesis of aneurysm of the internal jugular vein, the loss of its capacity function hampering blood outflow from the cranial cavity is of leading importance. Disorders in cerebral hemodynamics registered in rheoencephalography were revealed in all the patients examined. In 40% of them, the signs of venous encephalopathy were noted. Thus, presence of an aneurysm is an indication for operative intervention. The operation under the conditions of growing organism together with elimination of aneurysm is aimed at restoration of capacity function of the internal jugular vein and ensuring of its growth. Circular resection of aneurysm with end-to-end suturing of the vein and extravasal plasty with the use of polyurethane perforated tubular protector cut in a screw-shaped manner is an adequate operation. PMID- 1453615 TI - [Use of ultraviolet irradiation of the blood after surgery in patients with tumors]. AB - The results of ultra-violet irradiation of the blood in 207 patients after performance of thoracoabdominal operation for cancer of the esophagus and stomach were analysed. The method permits to reduce the incidence of postoperative complications, manifestations of endogenous intoxication, contributes to improvement in metabolic processes, and normalization of the state of the patients. PMID- 1453616 TI - [Preclinical study of the general toxic effect of polyplatillen]. AB - Toxic action of polyplatillen, a principally new platinum compound, was studied on laboratory animals and cell culture. When compared with cis dichlorodiamminplatinum, the preparation is 10-fold less toxic in animals and 100 fold--in the cellular systems. Reversibility of damaging action of polyplatillen at "non-toxic" dosages conditions the perspectiveness of its further clinical trials. PMID- 1453617 TI - [Radiologic diagnosis of Payr disease in children]. AB - The experience with diagnosis of Payr disease in 119 children with the use of a roentgenologic method, in particular, irrigoscopy was summarized. Falling of the right colic flexure with formation of abrupt kinks of the transverse colon, and retention of contrast substance in the right portion of the large intestine are the main roentgenologic signs of the Payr disease. PMID- 1453618 TI - [Ultrasound diagnosis of pyloric stenosis in young children]. AB - The results of observation of 12 children ranging in age from 1 to 4 mos with tentative diagnosis of pyloric stenosis are presented. The study was performed by special method, using "Aloka" SSD-280 (Japan) ultrasound apparatus. The characteristic symptoms of the disease were revealed in 9 children, diagnosis of pyloric stenosis was confirmed by means of endoscopy, palpation, and intraoperatively. The use of US is practically harmless, and can completely substitute for a roentgenologic method in detecting the given congenital pathology. PMID- 1453619 TI - [Current functional methods for investigating the rectoanal region in children]. AB - Continuous rectoanal profilometry and electromanometry with the use of original three-channel "Electronika A-1" apparatus were performed in 40 children. The technique for performance of investigations is described, the scheme for deciphering of the results is given. PMID- 1453620 TI - [Hemosorption with the use of porcine spleen in the treatment of purulent-septic diseases in children]. AB - In 14 children with purulent septic diseases, the method of biohemosorption with the use of a porcine spleen was used. In 13 children, the treatment was effective. One child with bilateral uretherohydronephrosis, pyonephrosis, urosepsis, signs of aggravating polyorganic failure died. The data obtained are indicative of the expediency to use biohemosorption for treatment of children with purulent septic diseases. PMID- 1453621 TI - [Diagnosis and therapy of tumors and tumor-like formations of the stomach and intestine in children]. AB - The experience with diagnosis and treatment of 45 children at the age of from 2 mos to 15 yrs with tumours and tumour-like formations of the stomach and intestine was summarized. Most frequently (more than in 60% of cases), lymphosarcoma was revealed, cancer--in 4.4% of cases. The main causes of diagnostic errors--ignoring the data of history, wrong interpretation of the results of palpation of the abdomen, incomplete examination of a patient and absence of oncologic suspiciousness in a physician. Results of treatment of the patients with malignant masses depended on a stage of the disease. PMID- 1453622 TI - [Comprehensive evaluation of long-term results of surgical treatment and principles of postoperative rehabilitation of children with anorectal atresia]. AB - The examination and treatment of 22 children at the age of from 2 to 14 years after surgical correction of fistulous forms of atresia of the anus and rectum was carried out. In all the patients, besides of general clinical investigations, the special studies of the large intestine with the use of roentgenologic and functional methods were performed. A scale-table for assessment of a degree of anal incompetence have been developed, criteria for choice of rational tactics for rehabilitation of the patients established. PMID- 1453623 TI - [Cysts and cyst-like formations of the abdominal cavity and retroperitoneal space in children]. AB - The results of surgical treatment of 29 children with cysts, and 10--with cyst like formations of the abdominal cavity and retroperitoneal space are described. In majority of the patients, a cyst at the terminal stage was revealed. In presence of complications, they were operated on with tentative diagnosis of acute appendicitis, or ileus. The operation consisted of cyst enucleation, its elimination with resection, or removal of the organ, creation of cystodigestive anastomosis. Postoperative lethality was 12.8%. PMID- 1453624 TI - [Immunocorrective effect of hemosorption in the comprehensive therapy of malignant tumors in children]. AB - In 25 children with malignant tumours of the retroperitoneal space and mediastinum, hemosorption was performed before and after operation in combination with chemotherapy with the aim of immunocorrection and detoxication of an organism. Under the influence of hemosorption, the general state of the patients improved, their immune status normalized permitting not to interrupt a course of chemotherapy. PMID- 1453625 TI - [The use of diagnostic and therapeutic colonofibroscopy in children]. AB - The results of investigation of the large intestine in 187 children were analysed. Of them, in 28 the terminal ileum was as well examined. In 38 patients with polyps and intestinal invagination, colonoscopy was performed in combination with endoscopy. Colonofibroscopy was used as a primary method of study to establish the causes of intestinal hemorrhage, colitis syndrome. The method has a high informative value, permits to extend the diagnostic and therapeutic possibilities in pediatric proctology. PMID- 1453626 TI - [Stages of intestinal invagination in children]. AB - The results of observation of 143 children with intestinal invagination are presented. In 105 patients, the disease was at the stage of compensation, in 27- subcompensation, in 10--decompensation. According to the data of clinical and laboratory investigations, the most pronounced changes in homeostasis were noted in children with intestinal invagination at the late stage. The measures aimed at stabilization of hemodynamics, improvement of microcirculation were carried out. In to the complex of treatment, the methods of extracorporeal detoxication of an organism and intestinal intubation going ahead of aggravation of toxemia were included. PMID- 1453627 TI - [Prognostic value of blood indices in children with acute appendicitis]. AB - The results of comparative analysis of blood formula, volume and cellular content of peritoneal effusion in children operated on for acute appendicitis are presented. In unfavourable course of the postoperative period, a significant decrease in content of neutrophil granulocytes in the peripheric blood and its increase in the peritoneal effusion as compared with the indices in the control group was noted. PMID- 1453629 TI - [Cryosurgical method of therapy for congenital vascular lesions in children]. AB - The experience with the use of a cryosurgical method in the out-patient treatment of 3112 children of different age with congenital vascular formations was summarized. In the total structure of neoplasms, capillary hemangioma was predominant. The original apparatus was used with exposure of from 10 to 45 sec. The results of follow-up of the patients for 2 to 5 years are presented. A good cosmetic and functional result was noted in 96.2% of patients. PMID- 1453628 TI - [Diagnosis and treatment of intestinal obstruction in children in the inter district pediatric surgery department]. AB - Within 25 years, 302 children with different forms of acquired ileus were treated at the inter-district surgical department. Intestinal invagination was revealed in 221 patient. In the complex of diagnostic and therapeutic measures, intravenous administration of "chromosmon", through insufflation of the intestine were employed. Intestinal intubation was performed by means of a magnet-dependent tube of original construction. Lethality was 0.3%. PMID- 1453630 TI - [Laparoscopy in the diagnosis of abdominal diseases in children]. AB - The results of laparoscopy performed in 1988-1990 in 112 children with tumours and cysts of the abdominal cavity, with diseases of the liver and bile ducts are presented. Of them in 60%, the puncture biopsy was performed. Use of laparoscopy in 64.28% of the sufferers with closed abdominal trauma permitted to avoid performance of needless laparotomy. For suspected acute appendicitis, laparoscopy was performed in 80 patients: in 36 of them, no signs of the disease were revealed, in 14--other diseases were detected, in 30--diagnosis was confirmed. A high informative value of the given method in the diagnosis of abdominal diseases in children was noted. PMID- 1453631 TI - [Methods for improving the surgical care of children]. PMID- 1453632 TI - [Study of large intestinal microflora in newborns with Hirschsprung disease]. AB - In 35 newborns and children at the age under 4 mos with Hirschsprung's disease, colonic microflora was studied. Disbacteriosis at phase 1 was revealed in 1 (2.9%) child, at phase 2--in 7 (20%), at phase 3--in 27 (77.1%). In acute form of Hirschsprung's disease, in 68.5% of cases, disbacteriosis at phase 3 with the signs of enterocolitis causing acute ileus was revealed. Intestinal perforation against background of enterocolitis developed in 8 cases. PMID- 1453633 TI - [Five-year experience in the work of the one-day pediatric surgery department]. PMID- 1453634 TI - [Antibiotic therapy of complications in surgical treatment of rectal cancer]. PMID- 1453635 TI - [The role of hypoxia and non-enzyme cationic proteins of leukocytes in the pathogenesis of acute post-operative purulent-inflammatory processes]. PMID- 1453636 TI - [A case of non-aspirated foreign bodies in the lung]. PMID- 1453637 TI - [Relapsing intestinal invagination in a child with Schoenlein-Henoch disease]. PMID- 1453638 TI - [Successful treatment of esophageal atresia combined with congenital duodenal stenosis]. PMID- 1453639 TI - [Peace-time gunshot injury in a child]. PMID- 1453640 TI - [Laser therapy of purulent-inflammatory diseases in children in ambulatory surgery]. PMID- 1453641 TI - [Transverse rupture of the pancreas in a child]. PMID- 1453642 TI - [Torsion of the appendix in a child]. PMID- 1453643 TI - [Congenital lobar emphysema in children]. PMID- 1453644 TI - [Effect of intravascular laser therapy on the rheologic properties of blood in children with bilateral destructive pneumonia]. AB - The effect of intravascular blood irradiation with helium-neon laser in 20 children with bilateral destructive pneumonia at a dose of 10-30 J/cm2 for a course of treatment on indices of hemostasis and rheologic blood properties was studied. Decrease in blood viscosity, hypocoagulative effect of intravascular laser therapy, normalization of clinico-roentgenologic data were revealed. PMID- 1453645 TI - [Laparostomy in a newborn]. PMID- 1453646 TI - [Isolated ectopy of the spleen in the thoracic cavity simulating lung tumor in a child]. PMID- 1453647 TI - [Trichobezoar of the ileum in a ten-year-old child]. PMID- 1453648 TI - [A case of lipoma of the scrotum in a three-year-old child]. PMID- 1453649 TI - [Lymphangioma of the retroperitoneal space in children]. PMID- 1453650 TI - [Hygroma of rare location in children]. PMID- 1453651 TI - [Torsion of the gallbladder in a six-year-old child]. PMID- 1453652 TI - [Condensing osteitis in children]. PMID- 1453653 TI - [The use of autohemolysate for hemostimulation in the combined and comprehensive treatment of patients with oncologic diseases]. PMID- 1453654 TI - [Modified technique of the Ivanissevich operation for varicocele in children]. AB - On the basis of the results of rheotesticulographic studies in 38 children with left-sided II-III degree varicocele, the impairment in hemodynamics in the testicle at the involved side was established. No suppression of androgen function of the organ was revealed. The expediency to perform in patients of pediatric and young age the Ivanissevich operation, the effectiveness of which is increased in use of intraoperative phlebotesticulography was noted. The effective method for varicocele treatment in children has been suggested. The testicular vein is ligated near the deep inguinal ring as well as at the level of the upper third, then it is excised between the ligatures together with the deviating branches. The method was used in treatment of 120 patients with II-III degree varicocele. No disease recurrence is noted during 1.5 years. PMID- 1453655 TI - [Value of dacryocystography in diagnosis of lacrimal duct diseases]. AB - The paper compares the preoperative localization of stenosis in the lacrimal passage after digital dacryocystography with the operative findings in 23 eyes of 22 patients in the years 1988 to 1991 at the Munich University Eye Hospital. In a very high percentage (95.6%) there is a positive correlation. The discussion shows the advantages of the method and includes a review of relevant literature. PMID- 1453656 TI - [Change in the etiology and sequelae of severe eye injuries. A comparison of 197 personal patient admissions with other reports from the literature]. AB - The spectrum of severe eye-injuries has clearly changed. We have analysed the documents of 197 patients treated in our clinic from 1988-1990. Of 119 (60.4%) contusions and 78 (39.6%) perforating injuries only 25.3% were occupational accidents. A more detailed analysis showed above all an increase of sport- and leisure-injuries and a considerable decrease of traffic-injuries (4.6%). Shocking is in contrast the percentage (10.7%) of severe injuries by brutality. More details concerning the consequences of injuries are presented and compared with older statistics. From this conclusions are drawn for better prophylaxis. PMID- 1453657 TI - [Aesthesiometry of the cornea after refractive corneal surgery]. AB - The corneal sensibility was examined with the aesthesiometer of Draeger in 41 patients after refractive corneal surgery, 31 patients after radial keratotomy, 5 after epikeratophakia, 5 after excimer laser ablation. It could be shown that after radial corneal incisions the sensibility remains normal. After epikeratophakia the corneal sensibility is asensible even 3 years after operation. The lenticle periphery shows an increase of sensibility after 6 months. Excimer patients with "haze" showed a significant hyposensibility in the centre. The central sensibility showed normal values after a normal corneal wound healing. PMID- 1453658 TI - [Results of the bimedial muscle belt]. AB - The effectivity of a retroequatorial muscle belt operation, modification of Cuppers' Fadenoperation, is demonstrated by its results in 206 patients with excess esotropia at near and variable angle esotropia. It is shown that this procedure can reduce excess esotropia at near by a significant amount and lessen the extent of variable angle esotropia without causing incomitance in horizontal eye motility. A belt, placed bimedially on both recti muscles, showed to be twice as effective on the deviation at near as on the angle at distance. Proposing a similar mode of action, the atraumatic fixation with the muscle belt can facilitate reoperations in comparison with the Fadenoperation. Damage to the muscle is limited to a minimum. PMID- 1453659 TI - [Persistence and transient conjunctival pathogen colonization before planned intraocular interventions]. AB - The risk of a postoperative endophthalmitis is influenced by the presence of a significant bacterial colonisation of the conjunctiva before intraocular surgery. Between February and August 1990 we performed conjunctival smears in 481 patients 1) on the eve of the operation and 2) just before planned intraocular surgery, to evaluate a persistent or transient microbial colonisation of the conjunctiva. 352 patients showed insignificant ("negative") and 129 patients a significant ("positive") bacterial growth in the first conjunctival smear. 96% of the patients (n = 336) had a negative result in both smears. 30% of the patients (n = 37) with a positive conjunctival smear showed a persisting bacterial colonisation, whereas 70% of the patients (n = 92) had a transient colonisation of the conjunctiva with a negative second smear. As a persisting microbial colonisation of the conjunctiva may be an important factor for the development of postoperative endophthalmitis, we recommend prophylactic conjunctival smears before surgery to diminish the risk of intraocular infections after surgery. PMID- 1453660 TI - [Clinical and fluorescein angiography findings in patients with retinal vein occlusion. A unicenter study of 211 patients]. AB - Between january 1986 and december 1989 we prospectively studied 211 patients with branch retinal vein occlusion (BRVO). Documented by fundus photography and fluorescein angiography clinical and angiographic findings were analysed. The age ranged from 28 to 83 with a mean of 63 years. 104 (48.8%) patients were male, 107 (51.2%) female. 51.1% right and 48.9% left eyes were affected. Mean visual acuity was 20/60. A non ischemic type of BRVO was found in 46.9% and an ischemic in 53.1% of the patients. The mean visual acuity in the non ischemic type was 20/50 and significantly better (p = 0.008) than in the ischemic type with a mean visual acuity of 20/60 (Mann-Whitney test). Preretinal neovascularisation was found in 14.7% and iris neovascularisation in 0.9%. One main branch was occluded in 82.9% and two main branches in 17.1%. The temporal superior quadrant was affected in 51.7%, the temporal inferior in 28%, the nasal inferior in 2.8% and the nasal superior in 0.5%. Hemisperical inferior BRVO were found in 8.1% and hemisperical superior in 5.7% of the patients. A BRVO in the fellow eye occurred in 8.5% and a CRVO in the other eye in 3.8%. Cystoid macular edema was present in 46.4%, a combination of cystoid and ischemic maculopathy in 23.7%, and ischemic maculopathy was found in 10%. Density of intraretinal hemorrhages was significantly (p = 0.046) and type of maculopathy highly significant (p < 0.0001) related to the ischemia type (Chi-square method). PMID- 1453661 TI - [Cosmetic lower eyelid blepharoplasties]. AB - Between April 1988 and December 1991 42 patients underwent a bilateral lower eyelid blepharoplasty. Depending on the etiology either a skin-muscle-flap or a skin-flap technique was used. When the lid was lax, it was shortened by a wedge resection to prevent postoperative ectropion. The results were satisfactory with either technique. PMID- 1453662 TI - [Extracapsular cataract extraction with phacoemulsification and pars plana vitrectomy with silicone oil tamponade in one session]. AB - BACKGROUND: In phacic eyes the development of a cataract is induced by silicon oil. In this case the lens has to be removed in a second operation with or without intraocular lens implantation. In cataract surgery a new incision technique is used, which makes it easily possible to combine both operations in one session. METHODS: A feature of the new incision technique is that a scleral tunnel is dissected before the anterior chamber is opened. The opening closes itself, if the intraocular pressure rises. The danger, that a rise in intraocular pressure during the vitrectomy makes an irisprolaps, for example during the substitution of perfluorcarbon by silicon oil, no longer exists. RESULTS: The operation technique and the postoperative course of three patients with intraocular lens implantation and pars-plana-vitrectomy using silicon oil is reported. CONCLUSIONS: By using the new incision technique in cataract surgery intraoperative complications during vitrectomy like an irisprolaps or penetration of silicon oil into the anterior chamber no longer exist. In selected cases one operation is saved for the patient. PMID- 1453663 TI - [A new program for calculating intraocular lenses]. AB - A principally new programme is described which overcomes the disadvantages of the usual calculation methods. It is based on the application of each surface of the optical system. The point for the anterior chamber lens is chosen in dependence on the anterior chamber depth; for the posterior chamber lens on the posterior surface of the eye lens. The programme is able to calculate 12 different cases. In each case calculations are made for intraocular lens power, aniseikonia and anisometropia. The calculations are made for possible emmetropia as well as for intended myopia or hypermetropia corresponding to the other eye. The programme can also be used to estimate the effect of mistakes made by measuring the single parameters, for instance: refraction, corneal curvature, eye length, anterior chamber depth. Compared to the SRK II-equation the results of the new programme are much more precise. PMID- 1453664 TI - [Alfred Th. Leber (1881-1954): a pioneer in tropical ophthalmology. Missing in the South Seas--rediscovered in India]. AB - In spite of the brief duration of German colonial rule during that period tropical medicine enjoyed a remarkable growth and development. This is the first account of the career of the pioneer of tropical ophthalmology, Alfred Theodor Leber (1881-1954); medical history had previously reported him missing in Java after the 1st world war. His career was greatly influenced by his uncle, Theodor Leber (1840-1917), the founder of experimental ophthalmology. Alfred Leber was the one who combined teaching and research in the subjects of ophthalmology and tropical medicine. During his first expedition as a private lecturer together with von Prowazek in Samoa (1910-1911), he discovered the involvement of the eye in filarial infections with Wuchereria bancrofti (Lebers fundus). In consideration of his extraordinary work he was appointed professor at the young age of 33. After his training at the eye clinic at Berlin University under von Michel he worked as senior physician with von Hippel in Gottingen. Both Ludwig Kulz and the famous painter Emil Nolde joined him on his second expedition, to New Guinea, in 1913. During his expedition in summer 1914 World War I broke out. Leber could not return to Germany. He stayed in the neutral Dutch East Indies during these years. Favoured by the ravages of war, British and Australian authorities (Military Intelligence, War Office, Defence) succeeded in seizing some of Leber's research reports and kept them under lock and key. The "Leber Kulz medical demographic New Guinea expedition on behalf of the Reich's Colonial Office" was therefore known to the public only as "Emil Nolde's travels in the South Seas".(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1453665 TI - [Clinical and histopathological observations of retinal sutures. Preliminary report]. AB - One of the therapeutical methods in the great hole and ora serrata retinal detachment are the retino-scleral sutures. The study evaluates the tolerance of this type of stitches. Experimental investigations have been performed in rabbits with sutures of Ethilon 8-0 or chromic collagen 8-0 put through the sclera. Both segments--the anterior and posterior one have been taken under consideration. The eye have been enucleated on the 1st, 2d, 7th, 14th and 60th day after surgery and evaluated macroscopically. The specimen from the spot of stitching have been executed after fixation in formaline. Clinical observations, macroscopic evaluation of the enucleated eyes and results of the histopathological examination showed good tolerance of the retinal stitches through the tissue of the rabbits eye and indicate the possibility of a clinical utilization of this method. PMID- 1453666 TI - [Detection of early cataract changes in the crystalline lens by using in vivo spectrophotometry of the eye]. AB - The aim of the paper was to study with the use of in vivo spectrophotometry of the eye the threshold values of the registered light above which one can observe clinically visible opacities of the lens. The performed experiments did not however show any major differences in the values of the registered light between persons with early cataract and control group because of considerable scattering of the results in both these groups. In order to explain the prognostic value of the in vivo spectrophotometry of the eye it is necessary to perform long-term observations of the further fate of persons with high values of the registered light. PMID- 1453667 TI - [Effect of cataract extraction on the results of in vivo spectrophotometry of the eye]. AB - The authors compared the results of in vivo spectrophotometry of the eye in persons with a normal lens, in patients with aphakia and after an operation of intraocular lens implantation. The results received show that in the range of 400 500 microns half of the light registered by the spectrophotometer is connected with the lens in the eye. This speaks for the assumption that in vivo spectrophotometry in this range of the wave length may be one more method enabling an objective evaluation of the transparency of the lens. In the case of patients after operation of implantation of an intraocular lens the quantity of of the light reaching the retina is only slightly larger than in persons with a normal lens. PMID- 1453668 TI - [The SRK formula for calculating the power of intraocular anterior-chamber lenses]. AB - Presented is the evaluation of the usefulness of the SRK formula for the calculation of the power of the intraocular anterior chamber lens of Pannu type. This accuracy is characterised by the value of the postoperative deviation of refraction of the operated eye. It has been noticed that the value of this deviation is fluctuating in the early postoperative period. Its stabilization comes out not before the 6th-9th month after surgery. This points out to the necessity of calculating the correcting coefficient A for the SRK formula into the late postoperative period. PMID- 1453669 TI - [Organization and the results of surgical treatment of cataract with implantation of artificial lenses in ambulatory conditions]. AB - Forty one patients aged 29 to 82 years were subjected to cataract extraction in ambulatory conditions. Fifty eyes were operated, among them 33 with implantation of a posterior chamber artificial lens. In cases of a lack of opacities in the cortex layers their structure was loosened before the operation by a YAG laser. The lens was extracted mainly by phacoemulsification. The ambulatory procedure did not result in any undesirable consequences. The profits of operation performed in such a way were stressed. Attention was called to the fact that by prudent qualification of patients and a careful selection of surgical methods the risk of this kind of treatment is not greater than in stationary conditions. PMID- 1453670 TI - [Cyclosporine in the treatment of uveitis]. AB - The study presents several years of observations concerning the application of cyclosporin in 2 cases of a very severe recurrent uveitis. The treatment by cyclosporin enabled to control the situation. In 1 case a cataract extraction was performed without complications. Both patients remain in observation of the out patients department. The treatment with cyclosporin requires observation of some precautions (control of function of the liver, kidneys etc.). No complications after cyclosporin therapy were seen. PMID- 1453671 TI - [Oral acyclovir treatment of viral eye infections]. AB - Forty four patients with virus conjunctivitis, keratitis, uveitis and retinitis were treated by acyclovir in tablets--5 times a day 400 mg.; the results were satisfactory. The drug was well tolerated and it could be used also in patients who showed hypersensitivity for acyclovir after ++intra-conjunctival application in the form of ointment. PMID- 1453672 TI - [Preliminary report on using therapeutic ozone in infectious conjunctivitis and keratitis and in corneal degeneration]. AB - The preliminary report presents the results of application of ozone preparation in form of ophthalmic drops in 89 patients (134 eyes). This preparation has been used in virus conjunctival and corneal diseases as well as in corneal degenerations after inflammatory conditions and chemical burns. One observed as acceleration of the regeneration processes in active inflammatory conditions of the anterior eye segment; instead the cases of leucoma and corneal opacities did not show any clinical effect. PMID- 1453673 TI - [Preliminary report on using general ozone therapy in diseases of the posterior segment of the eye]. AB - Autotransfusion of ozone venous blood was performed in 174 patients, in 32 patients ozone was given intraarterially. General ++ozone therapy was used for the first time in Poland in the following ophthalmological conditions: retinal pigment dystrophy, glaucomatous optic atrophy, in optic neuritis, after injuries and in cases of unknown aetiology; in degenerative-atrophic changes of the choroid, in high myopia, in post-inflammatory cases, in other degenerative diseases and in bacterial corneal ulcerations. Ozone therapy in these conditions seems to be favourable especially when the pathological process is not extensive. One could observe an improvement of the visual acuity and of the visual field. PMID- 1453674 TI - [Personal experiences with transplantation of antigenically compatible cornea. Preliminary report]. AB - Ten corneae from donors selected in respect of partial compatibility of the HLA antigens were transplanted in the period October 1988--October 1989. The grafting was performed in 10 patients with leukomas included in the group of maximal risk (5+). In 9 patients the leukomas were due to ocular burns (chemical in 8 patients and thermal in 1 patient). In 1 patient, a 74 years old man the grafting was performed in the single eye with Salzman's corneal dystrophy with a simultaneous cataract extraction. During observation, which lasted 2 to 12 months 6 grafts remained transparent, 1--partly opacified. Not any transplant did totally opacify. PMID- 1453675 TI - [Transplantation of the cornea from the donor selected on the basis of HLA compatibility in high risk leukoma]. AB - Fifteen corneal grafts were performed in 15 men with high risk leukoma (5+) in the period October 1988--November 1990. The age of the patients oscillated between 11 and 76 years. In 5 patients the grafting was done in only eye. The period of observation after surgery amounted 4-29 months. The favourable results (transparent and ++semi-transparent grafts) were obtained in 9 eyes (60 p.c.) and partly opacified grafts in 6 (40 p.c.). Neither of the grafts opacified. In the preceding years--without taking into account the antigenic selection of the donor -favourable results in similar leukoma cases were achieved in ca. 42 p.c. of cases. PMID- 1453676 TI - [Preliminary results of laser coagulation of the retina in the treatment of diabetic retinopathy in pregnant women]. AB - The authors observed a group of 16 pregnant women aged 22-38 years with insulin dependent diabetes of D, R, RF class (accor. to White). All the patients were treated by conventional insulin therapy. The fundus in 8 of them (16 eyes--group 1) was normal, in following 8 the fundus showed changes of the type of simple retinopathy (13 eyes--group 2) and proliferative retinopathy (3 eyes--group 3). Laser photocoagulation of the fundus changes was executed in 9 eyes. In the final period of gravidity the group 1 and 2 did not exhibit any new changes or intensification of the already existing; this could be connected with application of an intensive conventional insulin therapy. All the eyes (group 1 and 2) except one showed stabilization of the retinal changes after laser treatment. PMID- 1453677 TI - [Laser photocoagulation as a completion of the surgical treatment of retinal detachment]. AB - Among 600 operated retinal detachments in the last 5 years (1985-1989) there was no tight closure of the retinal hole after operation in 78. The causes were: the implant situated paracentrally to the hole, lack of contact between the implant and the hole, an insufficient scar, additional hole. Various types of the performed surgery were analyzed: the meridional or parallel implant, the balloon and endotamponade with the SF6 gas, executed with and without drainage of the subretinal fluid. In cases in which in the postoperative course was detected a lack of tightness of the hole the laser photocoagulation was performed in the area of the flat retinal detachment on the implant in a couple of stages. A favourable result of photocoagulation was attained in 75 patients (96.2 p.c.); in the remaining 3 patients (3.8 p.c.) a second surgical procedure was performed. PMID- 1453678 TI - [Hereditary macular degeneration in 3 generations]. AB - The family was described, where the vitelliruptive macular degeneration with various morphological picture was diagnosed in four persons (two males and two females) on the basis of ophthalmoscopic examination as well as fluorescein angiography. Morphologic variability of this dystrophy may lead to diagnostic difficulties, what previously caused unnecessary treatment of two examined men as cases of "central choroiditis". PMID- 1453679 TI - [6 cases of bilateral melanoma of the uvea]. AB - Six patients with bilateral ocular melanoma were treated in the period 1967-1989. In one case both eyes were enucleated, in 4 one eye only, the other eye was treated. In all enucleated eyes the clinical diagnosis of melanoma was confirmed histopathologically. Two patients died because of metastases to the lungs and liver, one is alive and remains in a periodical control; there are no informations on the remaining 3 patients. PMID- 1453680 TI - [Familial occurrence of congenital aniridia]. AB - Aniridia and coloboma iridis are congenital defects which are inherited in common as an autosomal dominant trait. The study presents an analysis of 15 pedigrees of 15 patients from 3 families; it confirms the hereditary character of aniridia and iris coloboma and indicates the variability of the genetic expression. PMID- 1453681 TI - [Evaluation of pupillary reaction to light flash in patients with retinitis pigmentosa]. AB - Twenty four patients with retinal pigment dystrophy were subjected to examination of pupillary reaction. Evaluated was the amplitude of pupillary reaction on a standard light flash. The results received were compared with the field changes. It was noted that the amplitude is diminished depending on the changes in the visual field. PMID- 1453683 TI - [Temporal arteritis]. AB - Presented is a case of a 74 years old patient whose ailment was diagnosed as Horton's disease (temporal arteritis) on the basis of general clinical symptoms (constant headache, sclerosis of the temporal artery, anorexia and sleeplessness) and ocular signs (poor visual acuity and pale papilloedema). PMID- 1453682 TI - [Internal ophthalmoplegia as a direct consequence of head injury. Report on 2 cases]. AB - The authors describe two cases admitted following head injury and presenting with a dilated, stiff pupil. CT scan of the head revealed no intracranial mass lesion. The symptoms persisted over a year in one case, whereas in the other one they faded away within a few weeks. The symptoms are believed to arise due to a downward shift of the brainstem which is known to occur at the moment of head injury. The oculomotor nerve is ++over-stretched and is supposed to be partially damaged at the posterior petroclinoid ligament. The roots of the pupillomotor fibers may also be supposedly torn at the site where they leave the brainstem. PMID- 1453684 TI - [Transplantation of the retina--the near or distant future?]. AB - In the review the results of the recently published experimental papers concerning transplantations of embryonic retina, retinal pigment epithelium and photoreceptors are discussed. The results of these studies indicate that in humans transplantation of the whole retina is the matter of the distant future but in the near future one can expect transplantation of the isolated retinal layers namely pigment epithelium and photoreceptors. PMID- 1453685 TI - Regulation of neurite outgrowth through protein kinase C and protease nexin-1 in neuroblastoma cell. AB - Accumulating evidence has demonstrated that protein kinase C (PKC) and protease nexin-1 (PN-1) may be involved in neuronal differentiation including migration, neurite outgrowth, target recognition, and synaptogenesis. We investigated the potential roles of PKC and PN-1 in neurite outgrowth of human neuroblastoma cell line, GOTO. Upon withdrawal of serum GOTO cells extended neurite processes within 3 h and formed fine network of neurites after 24 h. This morphological change was completely inhibited by thrombin and phorbol-12-myristate-13-acetate (PMA). Withdrawal of serum increased the neurofilament (NF)-L and -M mRNA levels and thrombin did not inhibit the effect of withdrawal of serum. A potent PKC inhibitor, H-7 induced neurite outgrowth in the presence of serum, however, it did not increase the NF mRNA levels. Actinomycin D and cycloheximide did not inhibit the initial neurite outgrowth induced by withdrawal of serum, while these inhibited the increase in the NF mRNA levels. Thrombin retracted the serum depletion-induced neurites but did not retract the neurites induced by H-7. The specific activity and subcellular localization of PKC did not differ between GOTO cells cultured in serum-containing and -free media for 12 h. The serine protease inhibitory activity was undetectable in the serum-free conditioned medium of GOTO cells but the PN-1 mRNA was clearly detected by Northern blot analysis to a less extent than glial cells. Withdrawal of serum or treatment with H-7 did not increase the PN-1 mRNA level in GOTO cells, but thrombin increased its level about 7 folds in serum-free condition. These results indicate that the initial neurite outgrowth requires neither new RNA nor protein synthesis, and that PKC negatively regulates neurite outgrowth and thrombin blocks neurite outgrowth through PKC-dependent pathways. PMID- 1453686 TI - Genetic changes in multi-step development of colorectal cancer. AB - We studied activated mutations of K-ras gene in three forms of colorectal tumors, i.e., 45 specimens of colorectal adenoma (CA), 10 of 'cancer in adenoma' (CIA), and 24 of colorectal cancer (CC), and in 15 of gastric cancer (GC) as controls. Chromosome aberrations were also examined in 7 specimens of CA, 3 of CIA, 8 of CC, and 7 of GC. Mutation of K-ras Codon 12 was observed in 12 (26.7%) of the 45 specimens of CA, 6 (60.0%) of the 10 specimens of CIA, 6 (25.0%) of the 24 specimens of CC, and 1 (6.7%) of the 15 specimens of GC. In CA, its frequency increased with the degree of histological atypism. In CA and CIA, its frequency increased with the increase in short diameter. The most frequent chromosome aberration was the numerical excess of chromosome 7. Numerical deficiencies of chromosomes 17 and 18 or structural abnormalities of 17p+ and 18q+ were noted in 1 specimen each of CA and CIA, and 2 of CC. Thus, aberrations of these two chromosomes were concurrent. 5q--was observed in 1 specimen each of CA and CC. These findings were not contradictory to the multi-step carcinogenesis model of the colorectum based on the hypothesis that carcinogenesis requires activation of an oncogene by mutation accompanied by defects of several genes that might normally inhibit tumorigenesis. PMID- 1453687 TI - Phosphorylation of CRE-BP1, a cyclic AMP response element binding protein, by protein kinase C and cyclic AMP-dependent protein kinase. AB - CRE-BP1 is a transcriptional activator binding to the cyclic AMP response element, which has a putative metal finger structure and the leucine zipper motif linked to a cluster of basic amino acids in the amino and carboxyl-terminal regions, respectively. The activities of a number of transcription factors are known to be controlled through phosphorylation and dephosphorylation. At the first step for understanding of the regulation of CRE-BP1, phosphorylation of CRE BP1 was studied in vitro. The human recombinant CRE-BP1 was phosphorylated by protein kinase C and cyclic AMP-dependent protein kinase. These two protein kinases recognized distinct seryl residues of CRE-BP1. Amino acid sequence analysis after phosphopeptide map indicated that two seryl residues, Ser-340 and Ser-367, located in the basic region of CRE-BP1 were identified as the major protein kinase C phosphorylation sites, whereas Ser-62 downstream of the metal finger structure was determined as the phosphorylation site by cyclic AMP dependent protein kinase. The phosphorylation of CRE-BP1 by these two protein kinases may regulate the function of this transcriptional activator protein. PMID- 1453688 TI - Multiple hormone secretion and gene expression in clones isolated from rat insulinoma cell lines. AB - Current evidence suggests that a multipotential endodermal cell may give rise to all islet cell phenotypes. Five (N1-N5) and twenty-one (m1-m21) pluripotent rat islet cell clones were isolated from two hormone-producing cell line (RIN-r, RINm5F) derived from a radiation-induced islet tumor. To investigate the characteristics of these clones, we analyzed the hormone expression and secretion by Northern blot, immunocytochemistry, and radioimmunoassay. Increased expression and secretion of insulin and glucagon were observed in these clones. The present examination might also be proof of the secretion of both insulin and glucagon in the single cell of the m21 clone isolated from RINm5F. These cell lines also overexpress the Ha-ras proto-oncogene. In order to determine whether or not the overexpression was caused by gene translocation, the insulin and Ha-ras gene loci in N3 isolated from RIN-r were assigned by in situ hybridization. Both of the genes were located on the long arm of chromosome 1, but no gene translocation was observed. These findings suggest that the expression of insulin and Ha-ras is not affected by chromosomal translocation, but it may be functionally linked in these clones. Overexpression of these three genes may indicate that these clones have the same characteristics as the embryonic immature islet cell. PMID- 1453689 TI - Evaluation of the viability and energy metabolism of ischemically damaged canine pancreas during preservation by the two-layer (University of Wisconsin solution/perfluorochemical) cold storage method. AB - We evaluated the viability and energy metabolism of ischemically damaged pancreas during preservation by the two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) cold storage method. The pancreas grafts subjected to 60-120 min warm ischemia were preserved by the two-layer (UW/PFC) cold storage method for 24 hours (group 3), a simple cold storage in UW for 24 hours (group 2) or without preservation (control) (group 1). The tissue concentration of adenine nucleotides (ANs) were determined using high performance liquid chromatography (HPLC) and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. The functional success rates of pancreas grafts of groups 1, 2 and 3 after 60 min of warm ischemia were 5/5 (100%), 4/5 (80%) and 5/5 (100%). After 90 min warm ischemia, the success rates of groups 1, 2 and 3 were 0/5 (0%), 0/5 (0%) and 5/5 (100%) respectively. Only the two-layer method (group 3) was effective for functional recovery of the pancreas suffered 90 min warm ischemia. However, after more than 105 min, the result was 0/5 (0%) in group 3. In groups 1 and 2, there was no correlation between the posttransplant viability and tissue concentration of ANs and energy charge potential (ECP) at the end of preservation. However, in group 3, there was an excellent correlation between the posttransplant viability and tissue concentration of adenosine triphosphate (ATP) and total adenine nucleotides (TAN) at the end of preservation. We conclude that tissue concentration of ATP and TAN at the end of 24 hour preservation by the two-layer (UW/PFC) method will predict the posttransplant outcome of pancreas graft subjected to significant warm ischemia. PMID- 1453690 TI - Attitudes, perceptions, and risk-taking behaviors of smokers, ex-smokers, and nonsmokers. AB - A sample of American adults completed questionnaires relevant to cigarette smoking. The questions were related to three areas: risk, perceptions of their or others' smoking, and satisfaction with life and health. The results revealed that smokers were greater risk-takers, that they perceived their smoking to be due to both physical and psychological addictions, and that they expressed less satisfaction and control. Results also indicated that smokers who saw their smoking as being addictive tended to be less satisfied with their health and felt less control over their lives. On the other hand, those smokers who were more likely to deny the health risks did not differ from either non- or ex-smokers on any of the satisfaction or control questions. PMID- 1453691 TI - Neuroticism and intensity of religious attitudes among clergy in England. AB - Ninety-two male and 20 female clergy completed the short-form Revised Eysenck Personality Questionnaire (Eysenck, Eysenck, & Barrett, 1985) and the Francis Scale of Attitude Towards Christianity (Francis & Stubbs, 1987). The findings support Eysenck's central theory regarding an inverse relationship between psychoticism scores and religious attitudes, and they confirm the view that neuroticism scores are also implicated in predicting the intensity of religious attitudes among the religiously committed. PMID- 1453692 TI - The effect of hypnotically elicited testimony on jurors' judgments of guilt and innocence. AB - Survey data from several countries indicate that many people believe that hypnosis may increase the accuracy of an eyewitness's memory; most experimental research, however, suggests that this belief is inaccurate. This study examined whether the belief could influence judgments of guilt and innocence in a simulated criminal trial. The results indicated that British undergraduates were more likely to find a male defendant guilty when told that the testimony against him had been elicited under hypnosis. Results concerning a nonhypnotic memory facilitation technique were found to be inconclusive, and the salience of hypnotically elicited testimony was ruled out as a contributory element. PMID- 1453693 TI - Love attitudes of white South African and British university students. AB - The Munro-Adams Love Attitude Scale was administered to 133 randomly chosen final year undergraduate White South African and British university students in this examination of their attitudes toward love, courtship, and marriage in relation to the observation that, although South African tertiary educational institutions exist within the authoritarian and restrictive culture of apartheid, they nevertheless are modeled on the British educational system, which has its roots deeply embedded within a politically democratic context. Results indicated that the South African sample's endorsement of the love attitude items was weaker, except for those pertaining to the power of love, than that of their British counterparts. In addition, the South African scores were lower than those previously reported in other similar cross-cultural research, and there was a differential ranking of the three love styles by the male and female subjects. PMID- 1453694 TI - Social perceptions of male and female extreme mesomorphs. AB - In this study, male and female university students in the United States were exposed to mesomorphic or nonmesomorphic stimuli as reflected by photographs of either male body builders and non-body builders or female body builders and non body builders. Then they were asked to attribute various personality traits and sex-role behaviors to them. Subjects, irrespective of their sex, perceived male and female body builders as possessing more traditionally masculine and less traditionally feminine personality characteristics than male and female non-body builders. Also, male and female body builders were seen as possessing less socially desirable traits than non-body builders. As predicted, female body builders were perceived generally as being more likely to engage in traditionally masculine sex-role behaviors in their dating and marriage relationships than female non-body builders. Contrary to expectation, however, male body builders were not perceived as more likely to engage in higher levels of masculine sex role behaviors than male non-body builders. PMID- 1453695 TI - Attribution of causes to suicide. PMID- 1453696 TI - Drug use and sexual behavior: users, experimenters, and abstainers. PMID- 1453697 TI - Optimal selection of metabolic fluxes for in vivo measurement. I. Development of mathematical methods. AB - The measurement of uptake and secretion rates is often not sufficient to allow the calculation of all internal metabolic fluxes. Measurements of internal fluxes are needed and these additional measurements are used in conjunction with mass balance equations to calculate the complete metabolic flux map. A method is presented that identifies the fluxes that should be selected for experimental measurement, and the fluxes that can be computed using the mass-balance equations. The criterion for selecting internal metabolic fluxes for measurement is that the values of the computed fluxes should have low sensitivity to experimental error in the measured fluxes. A condition number indicating the upper bound on this sensitivity, is calculated based on stoichiometry alone. The actual sensitivity is dependent on both the flux measurements and the error in flux measurements, as well as the stoichiometry. If approximate physiologic ranges of fluxes are known a realistic sensitivity can be computed. The exact sensitivity cannot be calculated since the experimental error is usually unknown. The most probable value of the actual sensitivity for a given selection of measured fluxes is estimated by selecting a large number of representative error vectors and calculating the actual sensitivity for each of these. A frequency distribution of actual sensitivities is thus obtained giving a representative range of actual sensitivities for a particular experimental situation. PMID- 1453698 TI - Optimal selection of metabolic fluxes for in vivo measurement. II. Application to Escherichia coli and hybridoma cell metabolism. AB - A method of analysis was presented in part I of this series for determining the fluxes in a biochemical network that are the optimal choices for experimental measurement. This algorithm is applied to two important biological models: Escherichia coli and a hybridoma cell line (167.4G5.3). Our results show that potentially poor choices for in vivo measurement of metabolic fluxes exist for both model systems. For the subset of reactions in E. coli that was studied, the condition number of the augmented stoichiometric matrix reveals that a 60-fold amplification of experimental error during computations is possible. The biochemical network of the hybridoma cell is more complex than the E. coli system, and thus results in much larger possible error amplification--up to 100,000-fold. The physiological situations appear to have sensitivities that are less than 1/4 to 1/10 of those estimated by the condition number, and the maximum sensitivities are proportional to the condition number. These maximum sensitivities calculated using estimates of the fluxes and the worst possible error vector are upper bounds on the system's actual sensitivity. By examining the effect of measurement error on the sensitivity, the most probable sensitivity is calculated. These results indicate that an approximate two-fold increase in sensitivity of the E. coli system is likely when the worst set of fluxes are measured rather than the best set. The most likely sensitivity of the hybridoma system can range three orders of magnitude, depending on the set of fluxes that are measured. The propagation of experimental error during computations can be diminished for both systems by increasing the number of flux measurements over and above the minimum number of experimental measurements. The findings from these two model systems indicate that the calculation of the condition number can be a useful method for efficient experimental design, and that the usefulness of this method increases as the order of the system increases. PMID- 1453699 TI - The eukaryotic CCAAT and TATA boxes, DNA spacer flexibility and looping. AB - Regulation of RNA transcription in eukaryotic polymerase II promoters involves a complex assembly of protein factors. Some of the factors bind to their cognate DNA-sequence elements while others mediate between the DNA bound ones. In order to enable protein-protein interaction, their spatial positioning with respect to each other is critical. Here two DNA-sequence-elements are investigated, the CCAAT and the TATA boxes and their spacers. Whereas the position of the TATA is fixed at about -30, that of the CCAAT can vary substantially from -50 to -200. Despite the variable loop sizes, the CTF (CCAAT-binding) protein interacts- either directly or indirectly via a co-activator--with the general basal TATA binding transcription factors. Sequence analysis of the spacers, as a function of their sizes, reveals that in the upstream regions of the spacers RR and YY are abundant. In the downstream, 3' region of the spacers RY and YR are very frequent. The DNA sequence elements and their intervening spacers are analyzed in terms of their geometry, anisotropic flexibility and local superhelical density. Our results indicate that the CCAAT and its vicinity is rigid, whereas the TATA and its surroundings is flexible. It is the large flexibility of this region in twist and in roll which allows DNA looping. General mechanistic implications for pol II promoters are discussed. PMID- 1453700 TI - Evolutionary aspects of mammalian secondary sexual characteristics. PMID- 1453701 TI - The pharmacology of extinction. AB - It is impossible to predict what compounds of pharmacological interest may be present in an unexamined species. The extinction of such species may result, therefore, in the loss of therapeutically significant compounds. The fact that science will never know what has been lost does not lessen the significance of the loss. A number of species are discussed to exemplify the potential loss. Ginkgo biloba is an ancient plant, apparently saved from a natural extinction by human intervention. From this tree, the ginkgolides have been isolated. These are potent inhibitors of platelet activating factor and hold promise in the treatment of cerebral ischemia and brain edema. Two species, the tree Taxus brevifolia and the leech Hirudo medicinalis, are threatened as a result of human activity. Both have recently yielded complex compounds of therapeutic importance. The antitumor agent, taxol, is obtained from T. brevifolia and the thrombin inhibitor, hirudin, is found in H. medicinalis. Catharanthus roseus, source of the anticancer agents vincristine and vinblastine, although not threatened, derives from a largely unexamined but severely stressed ecosystem of some 5000 plant species. In other examples, ethnobotanical knowledge of certain plants may be lost while the species survive, as exemplified by the suppression of the Aztec ethnobotany of Mesoamerica by the invading Spanish. Finally, the fallacy of the 'snail darter syndrome', where species may be viewed as too insignificant to worry about, is exposed by consideration of the pharmacological activities of a sea hare (a shell less marine mollusc) and various leeches. PMID- 1453702 TI - Kava: an overview. AB - Since the first significant contact with Europeans in the 18th century, the Oceanic plant, Piper methysticum Forst. (Piperaceae) and the beverage prepared from it, both of which are called kava, have become familiar to much of the outside world through both the written and visual media. The ceremonial preparation and consumption of the beverage are probably its most conspicuous and spectacular features. Kava continues to occupy a central place in everyday life in the islands concerned, although its role has been somewhat diminished by time and outside influences. Despite the large body of literature on kava--about 800 entries are listed in a recent bibliography by Singh (1986)--there has been no comprehensive review on the subject. Earlier contributions by Keller and Klohs (1963) and Shulgin (1973) were selective in treatment and dealt primarily with chemical and pharmacological aspects. The monograph by Steinmetz (1960) remains a standard reference but understandably some of the information in it has become dated. The attention of the reader is also drawn to two excellent additions to the recent kava literature, by Lebot and Cabalion (1988) and Brunton (1989), which are, although somewhat restricted in focus, are very significant contributions to the subject. The present review paper provides an updated and a multidisciplinary overview of the subject. It was prepared on the basis of the author's personal experience--he is a native of Fiji and lived in that country for about 30 years--as well as the relevant literature listed in the Singh (1986) bibliography and some more recent publications. PMID- 1453703 TI - Inventory of plants used in traditional medicine in Somalia. II. Plants of the families Combretaceae to Labiatae. AB - Fifty-nine plants are listed, which are used by traditional healers in the central and southern parts of Somalia. For each species are listed: the botanical name with synonyms, collection number, vernacular name, medicinal use, preparation of remedy and dosage. Results of a literature survey are also reported including medicinal use, substances isolated and pharmacological effects. PMID- 1453704 TI - Preliminary pharmacologic evaluation of crude whole plant extracts of Elephantopus scaber. Part I: In vivo studies. AB - Elephantopus scaber has been used in Brazil as a traditional remedy to cause diuresis, antipyresis and to eliminate bladder stones. In the current study, aqueous and hydroalcoholic extracts of whole plants were tested for acute toxicity, analgesic, antipyretic, antiinflammatory, cardiovascular, diuretic and constipating activities. Both extracts (0.3-6 g/kg i.p.) induced writhing, loss of muscle tone, ataxia, prostration and death in mice. No analgesic effects of these extracts were detected using mouse hot-plate and acetic acid-induced writhing tests. Both extracts failed to modify diuresis or carrageenan-induced rat paw edema. In contrast, given intraperitoneally, both reduced brewer's yeast induced hyperthermia in rats, but when given orally did not affect it. Moreover, the aqueous extract decreased the intestinal transit time in mice while the hydroalcoholic extract increased it. Finally, these extracts, given intravenously, reduced blood pressure and heart rate in rats; these effects could be blocked by atropine but not by co-administration of pyrilamine and cimetidine. PMID- 1453705 TI - Antimicrobial activity of Acacia nilotica (L.) Willd. ex Del. var. nilotica (Mimosaceae). PMID- 1453706 TI - Activities of Chromolaena odorata (Compositae) leaf extract against Pseudomonas aeruginosa and Streptococcus faecalis. PMID- 1453707 TI - Maternity and medicinal plants in Vanuatu. I. The cycle of reproduction. AB - Ethnobotanical data collection to select pharmacologically active species was carried out within a clearly defined therapeutic context: those plants used during the course of a woman's reproductive life. Extensive bibliographical and field data collection and cross-examination of the information thus gathered have provided us with a clearer picture of the effectiveness of these plant species. Various concepts, behaviours and practices relating to menstruation, pregnancy, birth and birth control were examined in detail from an ethnopharmacological point of view. A list of selected species of particular interest is proposed for further study. PMID- 1453708 TI - The tradition of medicinal plants in Zagori, Epirus (northwestern Greece). AB - Traditional herbal medicine in the Zagori region of Greece was studied by obtaining information from users and collecting herbs. In addition, traditional remedies found in old manuscripts and books were compared with those currently used in modern literature. The 36 medicinal plants used today are listed, including their common and scientific names, indications (some new) and recipes for preparations. PMID- 1453709 TI - Ethnobotanical study in River Tenes valley (Catalonia, Iberian Peninsula). AB - An ethnobotanical survey was carried out in the River Tenes valley, in an area of 260 km2 not far from the city of Barcelona. Although this setting might suggest that the area was unsuitable for research of this kind, the variety of microclimates--which implies a rich flora--and the existence of small villages and isolated houses made it possible to obtain valuable information. We obtained data on 209 species belonging to 60 families and here we present our findings on the properties, preparations and uses. PMID- 1453710 TI - Antibiotic screening of medicinal plants of the British Columbian native peoples. AB - One hundred methanolic plant extracts, 96 of which had documented medicinal uses by British Columbian native peoples, were screened for antibiotic activity against 11 bacterial strains. Eighty-five percent were found to have significant antibiotic activity against at least two of the bacteria tested. Ninety-five percent of the plants categorized as potential antibiotics based on their ethnobotanical usage were found to exhibit significant antibiotic activity. Seventy-five were found to be active against methicillin-resistant Staphylococcus aureus, 46 were active against an antibiotic supersusceptible strain of Pseudomonas aeruginosa and 18 of these were also active against a wild type strain. The extracts with the broadest spectra of activity were prepared from: Alnus rubra bark and catkins, Fragaria chiloensis leaves, Moneses uniflora aerial parts, and Rhus glabra branches. PMID- 1453711 TI - Brine shrimp bioassay screening of two medicinal plants used by the Warao: Solanum straminifolium and Virola surinamensis. PMID- 1453712 TI - Folk uses of some lichens in Sikkim. PMID- 1453713 TI - Thrombolysis and postinfarction ventricular septal rupture. AB - We studied all patients with postinfarction ventricular septal rupture referred to the Oxford Heart Centre for operation over a 4 1/2-year period. Twenty one women and 8 men were admitted to the Centre, 13 of whom had received streptokinase and 16 of whom had not. The median interval between symptomatic onset of myocardial infarction and the development of septal rupture was 24 hours for those treated by early thrombolysis (all streptokinase) and six days for those who were not. Of the 26 patients who underwent surgical repair, three were operated on less than 36 hours after streptokinase infusion, in one case within 12 hours of thrombolytic treatment. Macroscopic observation of the disintegrating myocardium showed muscle bundles dissected by blood rendered incoagulable by thrombolytic treatment, together with the histologic features of reperfusion injury. The overall surgical mortality rate for the streptokinase group was 33% and for the others 21%. The patient operated on within 12 hours of thrombolytic treatment recovered uneventfully. Six of seven surgical deaths were caused by left ventricular or biventricular failure and one by gastrointestinal hemorrhage. All survivors were in New York Heart Association classes II or III between 2 weeks and 4 1/2 years after operation. We conclude that thrombolysis leads to early breakdown of the interventricular septum after acute myocardial infarction but does not preclude early repair. PMID- 1453714 TI - Differential effects of advanced age on neurologic and cardiac risks of coronary artery operations. AB - Two thousand patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were prospectively studied to compare the influence of age on the incidence of neurologic, cardiac, and other complications. Postoperative neurologic events were found in 56 (2.8%) patients, with an incidence in patients > or = 75 years (8.9%) more than twice that of patients 65 to 74 (3.6%) and nine times larger than in patients < 65 (0.9%). Cardiac complications did not differ between age groups except for low cardiac output state, which occurred 1.7 times more frequently in patients > or = 75 years compared with those < 65. Patients with postoperative neurologic events had a ninefold increase in mortality--35.7% versus 4.0%. Logistic regression analysis demonstrate the most important predictors of a postoperative neurologic event to be age, preoperative neurologic abnormality, recent myocardial infarction, and duration of cardiopulmonary bypass. The risk of neurologic complications increases disproportionately to the risk of cardiac complications in the elderly undergoing coronary artery bypass grafting with cardiopulmonary bypass. Despite neurologic improvement (32 of 56 patients), a postoperative neurologic event was second only to low cardiac output state as the postoperative complication most highly associated with in-hospital death. These results are important for decisions regarding selection of candidates for coronary artery bypass grafting and for prediction of surgical outcome. PMID- 1453715 TI - Risk factors for stroke after coronary artery bypass. AB - To determine the prevalence of stroke after coronary artery bypass grafting and to evaluate risk factors, we reviewed the records of 1000 patients undergoing coronary bypass within a 1-year time period. Demographic and perioperative data were evaluated by chi 2 analysis. A history of diabetes, evidence of mural thrombus, positive oculopneumoplethysmography findings, increased age, aortic calcification, and postoperative arrhythmias all correlated with increased risk of permanent neurologic deficit for the patient undergoing coronary bypass. Risk factors were analyzed with stepwise logistic regression. A history of diabetes, presence of mural thrombi, and aortic calcification carried a higher probability that the patient would have a permanent neurologic deficit. PMID- 1453716 TI - On-line intraoperative quantitation of regional myocardial perfusion during coronary artery bypass graft operations with myocardial contrast two-dimensional echocardiography. AB - We hypothesized that the success of coronary artery bypass graft operations could be assessed by means of on-line quantitative myocardial contrast echocardiography. Accordingly, myocardial contrast echocardiography was performed at baseline and after each placement of venous graft in 21 patients undergoing coronary artery bypass graft operations. Time-intensity plots were generated on line with the use of a dedicated computer system, and areas under the curve were assessed for each injection. Successful on-line quantitation of myocardial contrast echocardiography data was performed in 17 patients; this allowed comparison before and after coronary artery bypass graft operations for 21 grafts, with agreement between expert visual analysis and quantitative data in 91% of these cases. Three distinct perfusion patterns were noted on myocardial contrast echocardiography: (1) reduced contrast effect before coronary artery bypass graft operations with improvement after coronary artery bypass graft operations (n = 11); (2) adequate contrast effect before coronary artery bypass graft operations with no change after coronary artery bypass graft operations (n = 9) (for patients in group 2, the mean percentage of coronary stenosis was less than the mean for patients in group 1-67% +/- 25% vs. 88% +/- 20%, p = 0.05); and (3) no contrast effect either before or after coronary artery bypass graft operations in one patient with previous infarction. One third of the time (34 of 95 injections), on-line quantitation was unsuccessful. Failure was related three times more often to problems associated with myocardial contrast echocardiography, such as attenuation and inadequate quality of bubbles, than to computer failure. Despite its limitations, on-line quantitative myocardial contrast echocardiography is feasible in patients undergoing coronary artery bypass graft operations and provides important objective information regarding the success of revascularization. PMID- 1453717 TI - A quantitative study of postoperative luminal narrowing of the internal thoracic artery graft in coronary artery bypass surgery. AB - We used quantitative angiography to determine the postoperative diameter of the internal thoracic artery graft at the point close to the anastomosed site in 147 patients who received the graft for the left anterior descending coronary artery. We performed generalized multiple linear regression analysis (Type I quantification method) to assess the effects of the following factors on the internal thoracic artery graft diameter: age, gender, time of angiography, laterality of the internal thoracic artery used, presence of an undivided major side branch of the internal thoracic artery, presence of a saphenous vein graft having blood flow competition with an internal thoracic artery graft, presence of distal stenosis of the recipient left anterior descending coronary artery, severity of postoperative left anterior descending coronary artery stenosis, and presence of coronary risk factors. The standardized category scores for 25% left anterior descending coronary artery stenosis, 50% left anterior descending coronary artery stenosis, and presence of a saphenous vein graft having blood flow competition with an internal thoracic artery graft were -1.418, -0.767 and 0.622, respectively. Thus, the internal thoracic artery diameter was smaller in patients with well-preserved flow of the recipient coronary artery. The internal thoracic artery diameter had a particularly strong correlation with the degree of left anterior descending coronary artery stenosis (partial correlation coefficient: 0.670). The other factors seemed to have little or no correlation with the postoperative internal thoracic artery diameter. With the criterion that the internal thoracic artery diameter below 1.0 mm represents the "string sign" of internal thoracic artery graft, this phenomenon was observed in nine patients (6.1%). In all of these patients, left anterior descending coronary artery flow was well-preserved, and no ischemia was disclosed in the left anterior descending coronary artery-perfused area. These results indicate that internal thoracic artery grafts have flow adaptability responding to the flow demand of the recipient coronary artery and that the string sign of internal thoracic artery grafts is mainly an outcome of its physiologic characteristics. PMID- 1453718 TI - Use of internal mammary artery in myocardial revascularization after mediastinal irradiation. AB - Ten patients with radiation-associated proximal coronary artery disease underwent myocardial revascularization. In seven patients (group A) the internal mammary artery was used and in the other three (group B) only venous conduits were used. Except for mild adhesions between the pericardium and the epicardium, no unusual technical problems were encountered. In all patients in group A the internal mammary artery exhibited excellent flow, and histologic examination in two patients revealed a normal intima and media with only slight fibrosis of the adventitia. In two patients in group B, fibrosis of the internal mammary artery precluded its use, whereas the third patient had contraindications prohibiting use of the internal mammary artery. Long-term follow-up (range 6 to 72 months) revealed that one patient in group A died late of metastatic disease, and of the remainder (nine patients), seven were in New York Heart Association class I and two were in class II. Preoperative assessment of the internal mammary artery by angiography or, alternatively, B-mode imaging with Doppler spectrum analysis is recommended in patients with radiation-induced coronary artery disease who are scheduled to undergo myocardial revascularization with intended use of the internal mammary artery. In our experience, despite previous exposure to irradiation, the internal mammary artery should still be considered as a viable conduit for myocardial revascularization when preoperative assessment shows patency. PMID- 1453719 TI - Direct imaging of the tricuspid valve annular motions by fiberoptic cardioscopy in dogs. I. Does De Vega's annuloplasty preserve the annular motions? AB - Applying the technology of direct imaging by fiberoptic cardioscopy, physiologic and pathophysiologic motions of the tricuspid valve anulus were studied in 10 anesthetized normal dogs (control group) and in 9 dogs that had chronic tricuspid regurgitation (TR group). The heart was perfused with transparent modified Tyrode's solution by working heart method, and the anuli, outlined by sutured beads, were observed and recorded on a high-speed video system in real time. Tricuspid valve annular area was calculated at 14 points during the cardiac cycle. The control group was studied in the normal condition, and the tricuspid regurgitation group was studied during four interventions: nontricuspid annuloplasty group and three tricuspid annuloplasty groups with reducing tricuspid valve annular area to 80%, 65%, and 50% of that of the non-tricuspid annuloplasty group by De Vega's procedure. Tricuspid valve annular area in the control group increased by 7% during atrial systole and was reduced by 34% mainly during ventricular systole, in which the free wall annular area and the septal annular area narrowed by an equal 34%. Chronic tricuspid regurgitation lessened tricuspid valve annular area narrowing to 20% in percent reduction (p < 0.01). In the TR group the decrease in tricuspid valve annular area narrowing was attributed mainly to lessened narrowing of the free wall anulus (percent reduction of tricuspid valve annular area, 19%; p < 0.01). The amplitudes in tricuspid valve annular area narrowing were unchanged in the tricuspid annuloplasty groups even when tricuspid valve annular area, was reduced to 50% by De Vega's tricuspid annuloplasty (percent reduction of tricuspid valve annular area, 16%; not significant). These findings suggest that De Vega's tricuspid annuloplasty is a reasonable method that does preserve the physiologic annular motions in the opening and closing mechanism of the tricuspid valve. PMID- 1453720 TI - Direct imaging of the tricuspid valve annular motions by fiberoptic cardioscopy in dogs with tricuspid regurgitation. II. Does flexible ring annuloplasty preserve the annular motions? AB - Applying the technology of direct imaging by fiberoptic cardioscopy in a working heart condition, we studied the tricuspid valve annular motions with flexible rings in nine dogs with chronic tricuspid regurgitation. Three annuloplasty studies with a totally flexible polytetrafluoroethylene ring, an elastic silicone ring, and a rigid metal ring were compared with a nonannuloplasty study. The annuloplasty was performed by reducing tricuspid valve annular area to 65% of that of nonannuloplasty condition. The anuli were observed and recorded on a videotape in real time. The three rings effectively reduced and remodeled the dilated anuli and improved the valve coaptation. The patterns of annular motions with the polytetrafluoroethylene and silicone ring were similar to that of normal anulus; the free wall anulus contracted centripetally, and the septal anulus moved toward the free wall side during systole. Pliability of both the anteroseptal and posteroseptal commissures with the flexible rings made these motions possible. The polytetrafluoroethylene ring followed a natural undulation of the anulus, whereas the silicone and rigid metal rings forced the annular planes to horizontal ones. Percent reductions of tricuspid valve annular area were 25%, 21%, and 23% in the nonannuloplasty, polytetrafluoroethylene, and silicone ring studies, respectively, without significant differences in annular contraction. In contrast, rigid metal rings completely disturbed the annular motions. These findings indicated that the two flexible rings did preserve the physiologic annular motions to the degree that the anuli had in the chronic tricuspid regurgitation condition. Especially, the totally flexible polytetrafluoroethylene ring preserved not only the annular motions but also the natural undulation, which resulted in reinforcing the valve coaptation. We believe that the flexible ring, especially a totally flexible one, is superior to the rigid ring in the aspect of reinforcing the valve coaptation to prevent further regurgitation. PMID- 1453721 TI - Excellent durability of the Hancock porcine bioprosthesis in the tricuspid position. A sixteen-year follow-up study. AB - From February 1975 to August 1981, 23 consecutive patients underwent tricuspid valve replacement, which was either isolated (six patients) or combined with the replacement of other valves (17) by means of a standard, glutaraldehyde-preserved Hancock porcine bioprostheses. Patients' ages ranged from 9 to 53 (mean 36.2) years. The follow-up period ranged from 0.2 to 16.5 years (mean 9.1) and was complete in 100% of all cases. Structural valve failure of the tricuspid Hancock valve was noticed in two patients, a 9-year-old boy and a 13-year-old girl 3.4 and 16.5 years after implantation, respectively. The actuarial freedom rate from structural valve failure at 10 years was 94 +/- 6%. There were six tricuspid prosthesis-related events: structural valve failure in two and valve thrombosis, anticoagulant-related bleeding, prosthetic valve endocarditis, and periprosthetic leak in one each, respectively. The actuarial freedom from these events at 10 years was 78 +/- 10%. Five pairs of aortic/mitral-tricuspid Hancock valves were explanted simultaneously from the same patients after 8.1 to 13.9 (mean 11.4) years postoperatively. A gross examination showed no valve dysfunction in the explants from the tricuspid position, but degenerative changes with valve dysfunction in those from the mitral and aortic position were observed (none of five versus five of seven; p < 0.03). We concluded that the selection of a Hancock bioprosthesis in the tricuspid position is acceptable because of the low incidence of prosthesis-related complications and the excellent durability of more than 10 years. PMID- 1453722 TI - Collins' solution for cold storage of the heart for transplantation must be reversed with cardioplegic solution before reperfusion. A functional and metabolic study in the rat heart. AB - The following hypotheses were tested using an isolated perfused working rat heart model: (1) Collins' solution for cold storage of the heart is harmful for the heart during reperfusion; (2) a "reverse" of the intracellular-type Collins' solution with an extracellular-type cardioplegic solution before reperfusion is able to prevent this disadvantage of Collins' solution. The following two major groups (I and II) and five subgroups (-a to -e) in each group were prepared. In group I (reversed group); the hearts were initially stored in Collins' solution but were reversed by a 1-minute flush with cardioplegic solution followed by storage in cardioplegic solution for the last 1 to 180 minutes of the total 3 hour storage, that is, groups I-a (reversed for 1 minute), I-b (10 minutes), I-c (30 minutes), I-d (90 minutes), and I-e (180 minutes). In group II (nonreversed control group); the hearts were stored in Collins' solution throughout 3 hours and were also divided into five subgroups of groups II-a, II-b, II-c, II-d, and II-e in which only a 1-minute flush with Collins' solution was performed at the point corresponding to group I. The coronary flow in any of group II showed a marked decrease during the early reperfusion period. In group I, however, the coronary flow increased significantly in proportion to the duration of the reversing phase. The recovery of the aortic flow and the cardiac output in group I showed a bell-shaped pattern in relation to the duration of the reversing phase, reaching their peak values when reversed for 30 minutes (group I-c). The prolonged reverse (180 minutes) resulted in a deterioration of functional recovery associated with a poorer preservation of high-energy phosphates and a larger enzyme leakage. These results suggest that the beneficial effects of intracellular-type Collins' solution for cold storage of the heart were further improved by reversing Collins' solution with the extracellular-type cardioplegic solution for the last 30 minutes of the 3-hour cold storage because the disadvantageous vasoconstriction due to Collins' solution during reperfusion was successfully prevented by the replacement of intravascular and extravascular Collins' solution with cardioplegic solution before the reperfusion. PMID- 1453723 TI - Polyethylene glycol-conjugated superoxide dismutase attenuates reperfusion injury when administered twenty-four hours before ischemia. AB - Covalent linkage of polyethylene glycol to superoxide dismutase prolongs the serum half-life of the enzyme and may facilitate intracellular access. We tested the myocardial protective effect of polyethylene glycol superoxide dismutase administered once, 24 hours before ischemia. Because hearts were studied ex vivo in a crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of polyethylene glycol alone, without conjugation to superoxide dismutase (n = 8); (3) PEG-SOD 10,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4) PEG-SOD 30,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of polyethylene glycol superoxide dismutase significantly reduce reperfusion injury when administered 24 hours before initiation of global ischemia. Moreover, since the perfusate was superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating superoxide dismutase. PMID- 1453724 TI - Nucleoside transport inhibition mediates lidoflazine-induced cardioprotection during intermittent aortic crossclamping. AB - The effects of pretreatment with the nucleoside transport inhibitor lidoflazine on repeated ischemia-reperfusion injury induced by normothermic intermittent aortic crossclamping were studied in canine hearts. Eighteen mongrel dogs were allocated to three groups: placebo (n = 6), lidoflazine (1 mg/kg) (n = 6), and lidoflazine (1 mg/kg) plus the adenosine receptor blocker aminophylline (7 mg/kg) (n = 6). Pretreatment was performed intravenously during 15 minutes before extracorporeal circulation. All hearts were subjected to four intervals of 15 minutes of global ischemia each followed by 10 minutes of reperfusion. After weaning from extracorporeal circulation, functional recovery was followed for 1 hour. In the lidoflazine group, myocardial adenosine content (0.25 +/- 0.06 mumol/gm dry weight) was 3.5 times higher than that in the control group (0.07 +/ 0.03 mumol/gm dry weight; p < 0.05) at the end of the last aortic crossclamping. The release of adenosine from the myocardium during each reperfusion period was significantly higher than that in the control group (p < 0.05). Myocardial extraction of lactate was normalized at every reperfusion interval in the lidoflazine group but not in the control group (p < 0.05). In the lidoflazine group functional recovery was significantly better than that in the control group. Positive rate of rise of pressure, negative rate of rise of pressure, and cardiac output recovered to, respectively, 150% +/- 19%, 82% +/- 8%, and 131% +/- 15% in the lidoflazine group versus, respectively, 37% +/- 9%, 23% +/- 7%, and 29% +/- 8% in the control group (p < 0.001) at 1 hour after extracorporeal circulation. When the adenosine receptor blocker aminophylline was administered in association with lidoflazine, protection dropped significantly: positive and negative rate of rise of pressure and cardiac output were, respectively, 58% +/- 8%, 46% +/- 9%, and 67% +/- 16% at 1 hour after extracorporeal circulation (p < 0.05 versus lidoflazine alone). These results suggest that the cardioprotective effects of lidoflazine are at least in part mediated by adenosine receptor stimulation via nucleoside transport inhibition-induced accumulation of endogenous adenosine in the myocardium. PMID- 1453725 TI - Effects of nucleoside transport inhibition on long-term ex vivo preservation of canine hearts. AB - The effect of nucleoside transport inhibition on 24-hour preservation of canine hearts was studied in 36 hearts arrested either with a cold hyperkalemic cardioplegic solution without (group I) or with supplementation of a specific nucleoside transport inhibitor (R75231, 1 mg/L) (groups II and III). The hearts were excised and stored for 24 hours at 0.5 degrees C. Then they were reperfused for 3 hours with use of a closed perfusion system primed with normal blood (groups I and II) or with blood supplemented with the same nucleoside transport inhibitor (0.32 mg/L) (group III). Serial biopsy specimens for determination of myocardial purines were taken. Creatine kinase and heat-stable lactate dehydrogenase release from the myocardium were examined during reperfusion. Recovery of function was studied during reperfusion by measurement of isometric contraction in a fluid-filled intraventricular balloon. After 24 hours of preservation, without the use of the drug, myocardial inosine and hypoxanthine accumulated to, respectively, 4.05 +/- 1.18 and 0.28 +/- 0.08 mumol/gm dry weight. In the drug-treated groups (II and III pooled), significantly less inosine and hypoxanthine accumulated (1.68 +/- 0.33 and 0.05 +/- 0.02 mumol/gm dry weight, respectively) (p < 0.05 versus group I). Upon reperfusion, intramyocardial adenosine was lost in the control hearts and maintained in the drug-treated hearts. Hypoxanthine accumulated significantly (p < 0.05) during reperfusion in group I (1.08 +/- 0.43 versus 0.16 +/- 0.13 in group II and 0.03 +/- 0.03 mumol/gm dry weight in group III). The rate of creatine kinase and heat stable lactate dehydrogenase release was significantly lower (p < 0.05) in group III (that is, pretreatment and posttreatment with the drug) than in the control group. Functional recovery of hearts in group III was superior to that in group II (p < 0.05), while hearts in group I showed no recovery at all. We conclude that nucleoside transport inhibition improves long-term preservation of the heart and that the mechanism of this protection may be related to an increase in endogenous adenosine and reduction of myocardial hypoxanthine content. PMID- 1453726 TI - Endothelial dysfunction caused by University of Wisconsin preservation solution in the rat heart. The importance of temperature. AB - The superiority of the University of Wisconsin solution over routinely used crystalloid cardioplegic solutions for myocardial preservation has been demonstrated in animal studies. We have investigated the effect of the University of Wisconsin solution at different temperatures on endothelial function by examining its influence on 5-hydroxytryptamine- and nitroglycerin-induced increase in coronary flow in the isolated rat heart. Thirty-eight rat hearts were perfused on a modified Langendorff preparation. In the control experiments, there was no significant difference in the percentage increase in coronary flow induced by 5-hydroxytryptamine and nitroglycerin after 30 minutes of perfusion with Krebs Henseleit buffer (n = 6). Continuous infusion of the University of Wisconsin solution for 30 minutes at 4 degrees C or at 10 degrees C did not alter the 5 hydroxytryptamine or nitroglycerin response. However, infusion at 15 degrees C reduced the 5-hydroxytryptamine-induced vasodilation, while at 20 degrees C the 5 hydroxytryptamine response was converted to vasoconstriction without a significant change in nitroglycerin effect (15 degrees C, 5-hydroxytryptamine, before: 30.2% +/- 1.5%, after: 6.0% +/- 1.0%, nitroglycerin, before: 28.8% +/- 1.3%, after: 31.2% +/- 1.8%; 20 degrees C, 5-hydroxytryptamine, before: 32.2% +/- 2.5%, after: -23.8% +/- 3.6%, nitroglycerin, before: 30.3% +/- 1.9%, after: 33.5% +/- 1.7%). Coronary vascular resistance in the control experiments rose from 55.0 +/- 2.5 cm H2O/ml/gm/min to 58.4 +/- 2.3 cm H2O/ml/gm/min (p = not significant). The increase after University of Wisconsin solution infusion at 4 degrees C and at 10 degrees C was similarly not significant. Coronary vascular resistance increased significantly following infusion of University of Wisconsin solution at 15 degrees C (p < 0.001) or at 20 degrees C (p < 0.01). We conclude that University of Wisconsin solution produces temperature-dependent endothelial dysfunction in the isolated rat heart. PMID- 1453727 TI - Renal function in patients undergoing cardiopulmonary bypass operations. AB - We evaluate short- and long-term effects on renal functional reserve of cardiopulmonary bypass in 11 patients. A selected group (persistence of renal functional reserve before operation) of 11 adult patients undergoing cardiopulmonary bypass for aorta-coronary bypass were studied. Renal functional reserve tests were performed in all patients before the operation, at postoperative day 9, and at 6 months after operation. Basal glomerular filtration rate did not show significant changes at 9 days and at 6 months after operation. On the contrary, renal functional reserve was absent at 9 days, but it was restored to preoperative levels at 6 months after operation. In conclusion, our data indicate that cardiopulmonary bypass probably causes renal damage that is not sufficient to influence routine renal function parameters. PMID- 1453728 TI - Does flow character of cardiopulmonary bypass make a difference? AB - The influence of pulsatile bypass flow on the performance of the cardiovascular system, fluids and blood balance, acid-base equilibrium, and splanchnic function was investigated. One hundred patients scheduled for elective coronary artery bypass grafting were randomly divided into a group of standard perfusion (NP) and a group of pulsatile perfusion (PP). At the end of the operation, similar cardiac performance developed in both groups that was higher than before bypass: left ventricular stroke work index after bypass, 56.8 +/- 2.7 gm/beat per square meter in the NP group and 56.7 +/- 2.6 gm/beat per square meter in the PP group (not significant). Further determinations did not differ among the groups. After discontinuation of cardiopulmonary bypass, bypass grafts flow measured using an electromagnetic probe did not differ among the groups. During the postbypass period, mean arterial pressure and systemic vascular resistance were similar (mean arterial pressure 86.8 +/- 1.6 mm Hg in the NP group and 88.5 +/- 1.7 in the PP group; systemic vascular resistance 817 +/- 33 dyne.sec/cm5 in the NP group and 881 +/- 34.5 in the PP group), as were further determinations. However, severe hypotension requiring the administration of vasoconstrictors was observed more frequently in PP group of patients (20 versus 6%; p < 0.05). Fluid balance determined at the second postoperative day was similar among the groups (+1307 +/ 239 ml in the NP group and +1535 +/- 266 ml in the PP group). Blood loss was 1122 +/- 120 ml in the NP group and 1263 +/- 119 ml in the PP group during the first postoperative day (p = 0.407). Urine output during bypass was lower in the PP group (261 +/- 25 versus 341 +/- 26 ml/hr; p = 0.028). The creatinine clearance was 96.4 +/- 10.3 ml/min in the NP group and 92.6 +/- 7.0 ml/min in the PP group (not significant); amylase and lipase clearance did not differ among the groups. Finally, no significant difference was detected in arterial lactic acid determinations and acid-base balance assessment between the groups postoperatively. Thus equivalent cardiovascular hemodynamics, a good control of fluids and blood balance, acid-base equilibrium, and a satisfactory protection of the function of kidneys and pancreas were obtained with both types of perfusion. PMID- 1453729 TI - The acoustic filter: an ultrasonic blood filter for the heart-lung machine. AB - Cardiopulmonary bypass-associated encephalopathy is thought to be due in part to continuous microembolization of the brain with gas microbubbles more than 40 microns in diameter during bypass. Current barrier filter technology cannot effectively remove such small microbubbles in fragile fluids such as blood. The design concepts for a new nonbarrier ultrasound-based fluid filtration system (an "acoustic filter") capable of filtering small microbubbles from blood are presented. The acoustic filter uses a field of high-intensity ultrasound to push microbubbles down an acoustic gradient, where they can be collected and removed. To test the filtration efficiency of the system, a Doppler ultrasound bubble detector was built. By monitoring the prefilter and postfilter Doppler signal an assessment of filtration efficiency was made. A suspension of stable albumin encapsulated microbubbles (4 to 32 microns) were used as a model of the microbubble contaminants that might be found in the arterial return line of the heart-lung machine. Inactivated, the acoustic filter neither removed nor added microbubbles to the fluid. Activated, the acoustic filter provided total or near total clearing of microbubbles. We conclude that the acoustic filter can remove microbubbles from a cardiopulmonary bypass-like apparatus. PMID- 1453730 TI - Intraaortic balloon pumping in patients requiring cardiac operations. Risk analysis and long-term follow-up. AB - The intraaortic balloon pump is usually the first mechanical device inserted for perioperative cardiac failure; however, little current information is available regarding short- and long-term effectiveness. From January 1983 through November 1990, 6856 adult patients underwent cardiac surgical procedures, 580 of whom (8.5%) had an intraaortic balloon inserted preoperatively (107 patients), intraoperatively (419 patients), or postoperatively (54 patients). There were 374 men and 206 women with a mean age of 63.9 years (range 19 to 88). Operations included 376 coronary artery bypass grafts, 100 mitral valve replacements (with or without bypass grafting), 70 aortic valve replacements (with or without bypass grafting), 15 double valve replacements (with or without bypass grafting), and 32 other procedures. There were 72 (12.4%) complications related to the balloon pump, of which 42 necessitated surgical intervention including thrombectomy (21), vascular repair (13), fasciotomy (2), aortic repair (1), and amputation (4). Operative mortality for patients supported by the balloon pump was 44%. Multivariate stepwise analysis of 27 parameters revealed six independent predictors of mortality: preoperative New York Heart Association class, transthoracic intraaortic balloon insertion (both p < 0.0001), preoperative administration of intravenous nitroglycerin, age, female gender, and preoperative balloon insertion (p < 0.001). Balloon-related complications were not predictive of death. Of the 326 hospital survivors, only 34 were lost to follow-up. There were 75 late deaths, the cause of which was cardiac in 41 (55%), noncardiac in 20 (27%), and unknown in 14 (19%). Actuarial survivals at 1, 5, and 9 years are 51%, 42%, and 33%. Of the 217 hospital survivors still alive and contacted, 81% were in class I (114) or II (60). These data demonstrate (1) operative mortality for patients requiring an intraaortic balloon in the perioperative period remains high, (2) perioperative risk factors can be identified, (3) complications related to the balloon pump do not affect survival, (4) operative survivors can achieve prolonged survival with excellent functional results, and (5) consideration for alternative methods of circulatory support is justified. PMID- 1453731 TI - Dynamic cardiomyoplasty acutely impairs left ventricular diastolic function. AB - In patients with congestive heart failure, medical treatment has a high rate of mortality and morbidity, and transplantation is limited by the availability of donor hearts. Dynamic cardiomyoplasty is being investigated as surgical therapy to improve left ventricular function in these patients. To evaluate the early postoperative effects of this procedure on left ventricular diastolic function, we studied seven dogs through the use of sonomicrometry and micromanometry in a canine model of dynamic cardiomyoplasty. Left ventricular diastolic parameters were determined before wrapping the latissimus dorsi muscle (baseline), after latissimus dorsi muscle wrap but without stimulation, and with synchronous left ventricular contraction-latissimus dorsi muscle stimulation. End-diastolic pressure was increased in both conditions after latissimus dorsi muscle wrap (without stimulation, 5 +/- 1; with stimulation, 6 +/- 2 mm Hg; p < 0.05) compared with baseline (3 +/- 2 mm Hg). The peak rate of diastolic pressure decay was greater at baseline (1560 +/- 370 mm Hg/sec) than after latissimus dorsi muscle wrap, both without (1260 +/- 330 mm Hg/sec, p < 0.01) and with (1120 +/- 420 mm Hg/sec, p < 0.01) stimulation. The constant of pressure decay was prolonged both without (53 +/- 10 seconds, p < 0.05) and with (62 +/- 11 seconds, p < 0.01) latissimus dorsi muscle stimulation compared with the baseline (38 +/- 5 seconds). Compared with baseline (0.2 +/- 0.2 cm-2), the constant of passive chamber stiffness increased after the latissimus dorsi muscle was wrapped around the heart (1.6 +/- 0.7 cm-2, p < 0.05) and with stimulation (2.1 +/- 1.0 cm-2, p < 0.01). The maximal diastolic filling rate (baseline, 18.1 +/- 6.7; without stimulation, 16.6 +/- 8.9; with stimulation, 16.6 +/- 4.1 cm2/sec, not significant) and end-diastolic short-axis area (baseline, 7.3 +/- 2.3; without stimulation, 7.4 +/- 2.1; with stimulation, 7.5 +/- 2.3 cm2, not significant) were similar among the three conditions. The latissimus dorsi muscle wrap prolonged relaxation and increased left ventricular passive stiffness. Synchronous latissimus dorsi muscle stimulation with left ventricular contraction did not improve diastolic function in this model. The results suggest that in the early postoperative period, dynamic cardiomyoplasty impairs diastolic function. PMID- 1453732 TI - High-dose intravenous beta 1-blockade in patients early after cardiac operations. Negative inotropism versus myocardial oxygen economy. AB - A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. Negative inotropic effects may outweigh the expected benefit, however. Against this background hemodynamic and metabolic effects of early postoperative infusion with the beta 1-selective agent metoprolol were studied in 22 patients after coronary operations. During basal postoperative conditions, intravenous metoprolol reduced cardiac index and stroke volume index compared with control patients, while other variables were unaffected. During the higher adrenergic level of a dopamine infusion (7 micrograms/kg per minute), the heart rate, rate pressure product, and myocardial oxygen uptake were attenuated in proportion to the plasma level of metoprolol. Intravenous beta 1-blockade did not affect the cardiac output or stroke volume responses to dopamine (the cardiac output was still, however, 19% lower than in control patients). A release of myocardial creatinine kinase isoenzyme myocardial band was observed during dopamine infusion, suggesting that myocardial ischemia was induced. The release was not influenced by metoprolol, but it correlated with heart rate (r = 0.60; p < 0.01). It is concluded that infusion of metoprolol early after coronary operations depresses myocardial contractility with some 19%, which was without clinical significance in straightforward patients; the increased myocardial metabolic demand during a period of increased adrenergic stress was attenuated by metoprolol. This may be of importance for myocardial recovery. PMID- 1453733 TI - Video-assisted thoracic surgical resection of malignant lung tumors. AB - Forty patients with malignant pulmonary disease underwent evaluation, staging, and a biopsy or resection by means of video-assisted thoracic surgery. There were 20 men and 20 women whose ages ranged from 27 to 82 years. Eight patients had a wedge resection for metastatic carcinoma, three a lobectomy for primary carcinoma, six exploration of the thorax, five biopsy of the aortopulmonary window, and eighteen a sublobar resection for primary carcinoma of the lung. There was no mortality. Three patients had air leaks that lasted an average of 8 days. Video-assisted thoracic surgery seems to be useful for more precise staging of carcinoma of the lung, and, in some patients, resectional operations can be performed. PMID- 1453734 TI - The role of mediastinoscopic biopsy in preoperative assessment of lung cancer. AB - Between 1970 and 1989, mediastinoscopy and thoracotomy were performed on 619 patients admitted to our clinic with lung cancer. When mediastinoscopy was analyzed by lymph node location, the highest sensitivity (95.7%) was for the left paratracheal nodes and the lowest (64.0%) was for nodes at the bifurcation (p < 0.01). The 5-year survivals according to the results of mediastinoscopy were 47% for negative results, 14% for false-negative results, and 6% for positive results. The 5-year survival rate however, was significantly higher (28%) in patients (n = 13) with positive mediastinoscopic findings who underwent complete resection of the primary tumor and all involved nodes than in patients (n = 78) who underwent incomplete resection (p < 0.01). These data support our opinion that patients with positive mediastinoscopic results should not always be excluded from treatment by thoracotomy. The role of mediastinoscopy is not to select patients for thoracotomy but to evaluate lung cancer at the pretreatment stage. PMID- 1453735 TI - Endothelin-1 mediates regional blood flow during and after pulmonary operations. AB - To investigate the role of endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells, in the physiologic response to surgical stress, we measured plasma endothelin-1 concentrations by a sandwich-enzyme immunoassay in patients with lung cancer undergoing pulmonary operations (n = 12). In the first group (n = 6), we measured plasma endothelin-1 concentrations at multiple sampling sites (median cubital vein, pulmonary artery, and left atrium). Plasma endothelin-1 levels were significantly increased at all sampling sites at the end of the operation. Although there was no difference between the increased plasma levels of endothelin-1 in the pulmonary artery and in the left atrium, the increased level in the median cubital vein (peripheral venous blood) was significantly higher than that in the pulmonary artery (mixed venous blood). This result suggests that the production of endothelin-1 might differ between various organs under surgical stress. In the second group (n = 6), we measured plasma endothelin-1 concentrations both in the median cubital vein and in the ipsilateral radial artery, and also measured cardiac output and forearm blood flow. The increase in endothelin-1 levels in the median cubital vein was significantly higher than that in the radial artery after the operation. The endothelin-1 output from the forearm, calculated by the forearm blood flow and the arteriovenous difference of endothelin-1 concentrations, significantly increased after the operation. Although the cardiac output significantly increased after the operation, the forearm blood flow significantly decreased. The present findings provide a novel hypothesis that the preferential release of endothelin-1 from the peripheral vasculature of the forearm may partly contribute to a compensatory response to surgical stress, for example, the reduction of local blood flow in nonvital organs so as to increase the blood flow in vital organs. PMID- 1453736 TI - Quantification of flow through an interatrial communication. Application to the partial Fontan procedure. AB - The partial Fontan procedure has become an accepted alternative for the high-risk candidate. Creation of a small right-to-left shunt will lower the systemic venous pressure and improve systemic cardiac output while maintaining an acceptable systemic arterial saturation. However, because of variations in patient size and postoperative transpulmonary gradient, proper sizing of the residual defect is difficult. We have therefore conducted a series of experiments on a model that simulates the blood flow across interatrial defects of varying sizes at several pressure gradients. We used porcine blood to develop guidelines for the sizing of the residual defect. Our results demonstrate a linear relationship between flow and pressure gradient across all hole sizes tested. In addition, there was a linear relationship between atrial septal defect size and flow at each pressure gradient. Our data show that the Gorlin formula predictions overestimated flow by 10% to 40%. It is evident from these data that relatively small changes in the size of the atrial septal defect or in the pressure gradient result in significant changes in flow. Therefore we advocate the use of an adjustable interatrial communication such as the snare-controlled adjustable atrial septal defect for patients undergoing partial Fontan procedures. PMID- 1453737 TI - Balloon dilation of stenotic aortic valve in children. An intraoperative study. AB - Ten children in the age range of 3 to 17 years with moderate to severe aortic valve stenosis (gradients of 55 to 109 mm Hg) underwent cardiac operations. At the time of the operation, during bypass, balloon dilation of the stenotic valve was performed and the results were visually assessed by the surgeon. Of the 10 consecutive cases, only three showed dilation results that were comparable to what seems optimal from a surgical point of view. The adverse effects in the remaining seven patients and the corrective measures taken were as follows: (1) too extensive a rupture requiring stabilizing sutures in one patient; (2) too short a rupture, requiring additional commissurotomy in three patients; (3) rupture into the valve leaflet, requiring valve suture and corrective comissurotomy in another three patients. This last, rather serious complication occurred in patients having functionally bicuspid valves with slightly thickened free valve edges, whereas valves with severely thickened edges ruptured in the commissure line but often to an insufficient degree. Because of the high incidence of suboptimal separation of the stenotic aortic valves with balloon dilation, we recommend that further evaluation of long-term results and identification of unsuitable cases should precede widespread use of the technique. PMID- 1453738 TI - Long-term results of survivors of surgical valvotomy for severe aortic stenosis in early infancy. AB - Long-term morbidity and mortality were evaluated in the 21 survivors of a cohort of 51 consecutive infants with severe aortic valve stenosis who underwent surgical treatment in the first 3 months of life during the period from 1958 to 1988. The 21 early survivors have been followed up from 3 to 27 years (median 7.5 years). There have been two late deaths: one at age 13 year from bacterial endocarditis and the other at age 14 years after dislodgment of a prosthetic valve. The calculated 10-year actuarial survival for this group is 100%, with a 15-year actuarial survival of 75% (standard error 15%). Seven repeat operations have been performed in six patients: Three had persistent stenosis and a repeat valvotomy was performed in two of them, aged 2 years and 15 years. The other underwent placement of a conduit from the left ventricle to the descending aorta at 2 years of age. Replacement of the aortic valve has been performed in four patients because of severe valvular insufficiency 13 to 27 years after the initial operation. One of these had required a repeat valvotomy at the age of 15 years. The calculated actuarial freedom from reoperation at 10 years is 90% (standard error 6%) and at 15 years, 67% (standard error 15%). Aortic insufficiency was progressive throughout the period of follow-up. No patient had more than moderate aortic insufficiency 3 to 5 years after the initial valvotomy, whereas aortic insufficiency was severe in five of the eight patients followed up for 11 or more years. Progression of aortic insufficiency and the need for reoperation were not related to the age at initial valvotomy. Survivors of surgical aortic valvotomy in early infancy have a relatively good long-term prognosis and a high freedom from reoperation in the period leading to adolescence. Aortic insufficiency in these patients is progressive, and valve replacement eventually may be required. PMID- 1453739 TI - The role of coronary artery abnormalities in the prognosis of truncus arteriosus. AB - A high incidence of coronary ostial and arterial abnormalities was found in a study of 30 pathologic specimens of classic truncus arteriosus at Children's Hospital of Pittsburgh. The following were of special note: (1) left coronary ostium in a posterior and high position; (2) close relation of the left coronary ostium to the pulmonary artery segment in three-leaflet truncal valves; (3) stenosis of the coronary ostium caused by small size, slitlike shape, or the location of the ostium above or in a commissure; (4) the acute angle takeoff of the coronary artery; (5) the position of the left anterior descending artery as it courses posteriorly and close to the truncal wall, and then to the left of the interventricular septum; (6) the size and course of the conal and diagonal arteries from the right coronary artery across the right ventricular outflow area; (7) other coronary abnormalities, including a single coronary artery or ostium with branches crossing the right ventricle below the truncus, the circumflex arising from the right coronary artery and coursing behind the truncus, and the right coronary artery originating from the left anterior descending artery and vice versa. Eight heart specimens with conduit repair were reviewed, and all had injury to coronary arteries, possibly responsible for or contributing to the deaths of six of the eight patients. Coronary abnormalities, often several occurring in combination, may contribute to high operative mortality rate and may be a cause of late sudden death in truncus arteriosus. Surgical procedures should be planned with a view to protecting coronary arteries in the region of the right ventricular outflow tract below the truncus. Coronary artery obstruction (ostial or luminal) can occur and may need to be addressed as a separate issue during surgical procedures. PMID- 1453740 TI - Assessment of myocardial ultrastructure after retrograde infusion of cardioplegic solution. PMID- 1453741 TI - Neutrophil activation during cardiopulmonary bypass. PMID- 1453742 TI - Autoperfusion of the heart and lungs for preservation with preserving the bronchial circulation. PMID- 1453743 TI - Acquired diffuse bronchomalacia in heart-lung transplant recipients. PMID- 1453745 TI - A third-degree burn associated with external cardiac pacing in a five-year-old boy. PMID- 1453744 TI - Invited letter concerning: rationale for wedge resection of peripheral lung cancers--evidence from vessel staining and rates of proliferation. PMID- 1453746 TI - Pulmonary atresia and intact ventricular septum associated with pulmonary artery sling. PMID- 1453747 TI - Transesophageal echocardiographic diagnosis of covert cardiac tamponade during extracorporeal membrane oxygenation in an adult. PMID- 1453748 TI - Establishing a pediatric cardiac surgical unit in the Commonwealth of Independent States (formerly the Soviet Union) PMID- 1453749 TI - Aorta-right ventricular tunnel with a rudimentary valve and an anomalous origin of the left coronary artery. PMID- 1453751 TI - Obstinate cases of stromal keratitis treated by combined traditional Chinese and Western medicine. AB - Twenty-two cases 23 eyes with obstinate stromal keratitis treated by combination of traditional Chinese and Western medicines are reported in this paper. According to clinical manifestations, they are consistent with the clinical diagnosis of stromal herpes simplex keratitis. Since no specific Western medicine is known to be effective in treating this disorder, it is proposed to apply systemic and topical TCM and, if necessary, add beta-ray irradiation to shorten the clinical course of disease, decrease or prevent recurrence and maintain useful visual acuity, avoiding frequent relapses leading to blindness. PMID- 1453750 TI - Clinical and experimental studies on tong yu ling in the treatment of diabetic hyperlipemia. AB - 72 diabetes mellitus patients (70 cases non-insulin-dependent) were treated routinely with D860. After one month, cases with persisting hyperglycemia and hyperlipemia were randomly divided into Group A to be treated with D860 plus Tong Yu Ling (TYL), and Group B to continue treatment with D860 alone, while Group C, comprising cases with persisting hyperlipemia only, were treated with TYL alone. Therapeutic results showed that of the total 50 cases of Group A and C, 26 were markedly improved, 14 improved, and 10 cases ineffective. The antihyperlipemic effect was pronounced in Group A, where the blood cholesterol, beta-lipoprotein and triglyceride showed remarkable decline, less pronounced in Group C, and insignificant in Group B. Experiments in rat models of non-insulin-dependent diabetes demonstrated that TYL was markedly effective in treating hyperlipemia. PMID- 1453752 TI - Treatment of tonic headache with acupuncture. AB - Headache is a common symptom of complicated etiology; treatment is often ineffective when the intrinsic cause of the manifestation is not identified. The author found that tonic headache was very common in Germany, where few patients were helped in spite of various modalities of treatment. Since acupuncture proved useful to many cases it is the author's wish to add this ancient practice to the armory of the medical profession. PMID- 1453753 TI - Treatment with acupuncture at zusanli (St 36) for epigastric pain in the elderly. PMID- 1453754 TI - 51 cases of occipital neuralgia treated with acupuncture. PMID- 1453755 TI - Analgesic effect of laser irradiation following surgical operation of the anus. PMID- 1453756 TI - The effect of radix Salviae miltiorrhizae on the changes of ultrastructure in rat brain after cerebral ischemia. AB - The effect of RSM on ultrastructural alterations of the cortical, hippocampal and caudate neucleus areas brought about by forebrain ischemia in rats were studied. In both RSM-treated and saline-treated groups the ischemic damage was detected in nearly all animals three hours after bilateral common carotid artery ligation, while it was much more mild in RSM-treated animals. The ultrastructural changes consisted of swollen mitochondria, partial loss of cristae, dilatation of rough endoplasmic reticulum and Golgi's complex. In addition, some dark neurons were present, capillary endothelial cells and processes of astrocytes were swollen and active pinocytosis appeared in the endothelial cells. Their presence was most severe in the hippocampus region and the least in the caudate nuclear area. No ultrastructural changes exhibited in the sham-operated animals. The findings of the present experiment demonstrate that RSM can reduce ultrastructural abnormalities of cerebral ischemia and are also direct evidence of the protective effect of RSM on cerebral ischemia. PMID- 1453757 TI - Mechanism of acupuncture in suppressing epileptic seizures. PMID- 1453758 TI - Experimental studies on the inhibition effects of 1000 Chinese medicinal herbs on the surface antigen of hepatitis B virus. AB - The reverse passive hemagglutination inhibition test was used in the screening of 1000 Chinese materia medica for inhibitors of hepatitis B virus surface antigen. The herbal drugs were commercially available and the surface antigen was from sera of hepatitis B patients. 127 effective drugs were obtained from the survey of which 28 were highly inhibitory (8:1), 35 were moderately effective (4:1), and 64 mildly effective (2:1). Further experiments with varying dosages of the drug, dosages of HBsAg and duration of contact showed 10 drugs to be of optimal effect. PMID- 1453759 TI - The feeling thought process during Qigong. PMID- 1453760 TI - Simplified massage therapy for acute uroschesis: a clinical report of 15 cases. PMID- 1453761 TI - Massage treatment of infantile congenital myogenic torticollis. PMID- 1453762 TI - Progress of research on ischemic stroke treated with Chinese medicine. PMID- 1453764 TI - Traditional Chinese methods of health preservation (2). PMID- 1453763 TI - Present status of research abroad concerning the effect of acupuncture and moxibustion on immunologic functions. AB - Japan is one of the countries that have done extensive research on the effect of acupuncture and moxibustion on the immunologic functions. With China first, Japan ranks second among the countries in this study. Concerning research in this field concerned the level abroad can scarcely reach that in China. Scholars abroad fail to base their research on TCM theory. In addition not only the type of diseases studied, and the indexes observed are far less than those in China, but also the scope of their research is far narrower. However, certain diseases under study (for instance, AIDS) and certain indexes under observation (for instance, analysis of changes in T subsets of lymphocytes with monoclonal antibodies), as well as certain aspects of their investigation are worthy of consideration by scholars in China. PMID- 1453765 TI - Acupuncture treatment of soft tissue injury. PMID- 1453766 TI - Auriculoacupuncture therapy--a traditional Chinese method of treatment. PMID- 1453767 TI - Combined therapy with all-trans-retinoic acid and high-dose chemotherapy in patients with hyperleukocytic acute promyelocytic leukemia and severe visceral hemorrhage. AB - Acute promyelocytic leukemia (APL) is associated with a high incidence of disseminated intravascular coagulation (DIC) and early hemorrhagic death. The risk of early fatal hemorrhage is increased when high peripheral-blood blast count and severe DIC accompanied by visceral hemorrhage are present at diagnosis. Progressive cytolysis induced by daily increased doses of chemotherapy, or differentiation all-trans-retinoic acid (ATRA) therapy have been proposed for initial control of DIC, but both are dangerous in hyperleukocytic APL patients. We report our results obtained in three high-risk APL patients treated with a combination of conventional chemotherapy and ATRA. All patients had documented hyperleukocytic APL [M3 or M3-variant subtype, (15, 17) translocation] with DIC, and all had critical clinical course before treatment. Patient 1 presented with cerebral hemorrhage, patients 2 and 3 had acute respiratory failure probably due to pulmonary leukemic infiltration and pulmonary hemorrhage. In order to minimize the severity of DIC during chemotherapy-induced acute cytolysis, ATRA (45 mg/m2 per day) was started on the first or second day of chemotherapy and withdrawn when complete remission (CR) was achieved. Despite adverse clinical features, CR was obtained in these three high-risk patients. Patient 1 showed no increase of cerebral bleeding during therapy. Patients 2 and 3 required transient intensive care, with mechanical ventilation from day 4 to day 11 for one of them. Differentiating granular cells were present in peripheral blood of all patients from the day 5, 12 and 8 of cytotoxic therapy. For the three patients, the number of days with white blood cell count < 1 x 10(9)/l was only 2, 7 and 11 days respectively. These results suggest that differentiation therapy with ATRA may be useful even in hyperleukocytic APL patients, when ATRA is used in combination with chemotherapy. The mechanisms of this putative beneficial effect are discussed. PMID- 1453768 TI - Clinical significance of monoclonal proteins in chronic lymphocytic leukemia. AB - Serum monoclonal proteins were found in 36 of 111 (32%) chronic lymphocytic leukemia (CLL) patients studied using high-resolution agarose gel electrophoresis combined with immunofixation. In contrast, using immunoelectrophoresis (IEP) and serum protein electrophoresis (SPEP), monoclonal proteins were found in 20 and 4% of CLL patients, respectively. The presence of a monoclonal protein was associated with a median survival of 63 months compared to 103 months for individuals without a monoclonal spike (p < 0.012). This was independent of clinical stage. The data also suggests that the presence of a monoclonal protein may define a group of patients at greater risk for disease progression in the low and intermediate risk groups. (Rai stages, 0, I, II). Further follow-up will be required to determine if this is statistically significant. PMID- 1453769 TI - The detection of Philadelphia chromosome negative metaphases in long-term bone marrow cultures of the peripheral blood from patients with chronic myeloid leukemia predicts response to interferon-alpha 2a. AB - The cytogenetic response of 10 patients with chronic myeloid leukaemia (CML) to human recombinant interferon-alpha 2a (rhIFN alpha 2a) was compared to the Philadelphia chromosome (Ph) status of the pre-treatment peripheral blood cells after in vitro culture under long-term bone marrow culture (LTBMC) conditions. Pre-treatment light density peripheral blood cells were cultured in LTBMC on sex mismatched irradiated allogeneic stromal layers with weekly cytogenic examination of metaphases in the non-adherent cell fraction. This was correlated with the patients' response to rhIFN alpha. Two groups of patients, five showing a cytogenetic response (responsive) and five who failed to achieve a cytogenetic response (nonresponsive) were studied. At the initiation of the LTBMCs the Ph' was found to be present in 100% of the cells analysed for nine patients and 97% for one patient. Pretreatment peripheral blood from four responsive patients demonstrated a decline in the proportion of Ph'-positive cells (Ph+) after 1 to 2 weeks in LTBMC. In contrast, peripheral blood from all the non-responsive subjects showed persistence of the Ph+ clone in 100% of the cells analysed out to a maximum of 3 to 5 weeks in LTBMC. A significant difference was observed (Fisher exact test, p = 0.023) between the two patient groups in respect to the appearance of normal clones in the nonadherent population. The presence of Ph- metaphases in LTBMC of peripheral blood cells of CML patients may predict their cytogenetic response to rhIFN alpha 2a. PMID- 1453770 TI - Abnormalities of chromosome 16q in myeloid malignancy: 14 new cases and a review of the literature. AB - Fourteen patients with abnormalities of chromosome 16q, 13 with acute myelogenous leukaemia (AML), and one with refractory anaemia with excess of blasts (RAEB), are described. Seven patients had inv(16)(p13q22), two had del(16)(q22), and five had other abnormalities of 16q. Six of the seven patients with inv(16) had AML M4Eo and, following treatment with adriamycin, cytosine arabinoside, and 6 thioguanine, all achieved complete remission (CR). Neither patient with del(16)(q22) had typical M4Eo morphology at diagnosis; CR was achieved in one and one had resistant leukaemia. Patients with other abnormalities of 16q had blasts of diverse morphology and, although morphologically abnormal eosinophils were seen in three patients, this was not as marked as in the patients with inv(16). CR was achieved in two of the four patients with other abnormalities of 16q but duration of remission was short in both cases. These results suggest that most patients with del(16)(q22) and other abnormalities of 16q22 do not have typical AML M4Eo. Such patients tend to have a worse prognosis, and are more likely to have complex karyotypes typical of secondary leukaemia. PMID- 1453771 TI - The CD4 molecule belongs to the phenotypic repertoire of most cases of acute myeloid leukemia. AB - In the present study fresh leukemic cells obtained from 23 patients with acute myeloid leukemia (AML; FAB subtypes: three M1, five M2, two M3, five M4, eight M5) were investigated for the membrane expression of the CD4 molecule by cytofluorimetric analysis with an anti-CD4 monoclonal antibody (mAb). In 15 cases the presence of the CD4 mRNA was also investigated using Northern blot analysis. Membrane expression of the CD4 molecule was demonstrated in 19 out of 23 cases, and it was found to be weaker than in CD4+ lymphocytes and monocytes obtained from normal controls. Full-length CD4 mRNA was detected in 12 out of 15 (80%) cases, and AML cells positive for CD4 mRNA expression also expressed the CD4 antigen. Since the CD4 molecule expressed by T cells is associated with p56lck, a member of the src family of intracellular tyrosine kinases, we investigated whether the CD4 molecule expressed by myeloid blasts is also associated with a tyrosine kinase activity. In vitro kinase assays performed on anti-CD4 immunoprecipitates from lysates of myeloid leukemia cells from four CD4+ cases were negative for the presence of a tyrosine kinase activity. This finding was not due to the lack of expression of members of the src family since we were able to detect at least p60src and p59fyn in myeloid leukemia cells. According to our results, the CD4 molecule seems to belong to the phenotypic repertoire of most AML, irrespective of their FAB subtypes. However, in myeloid blasts this molecule is not associated with a tyrosine kinase activity as it occurs in T lymphocytes. PMID- 1453772 TI - Differences in the intracellular pharmacokinetics of cytosine arabinoside (AraC) between circulating leukemic blasts and normal mononuclear blood cells. AB - The increasing insights into the pharmacokinetics and the metabolism of cytosine arabinoside (AraC) have improved the rationale for its application in leukemia therapy and have led to a pharmacologically directed design of antileukemic treatment. The current study aims at adding to this approach by detecting differences in the intracellular metabolism of AraC 5'-triphosphate (AraCTP) between leukemic and normal mononuclear blood cells. Measurements of intracellular AraCTP levels were complemented by determinations of plasma AraC and AraU concentrations and were performed in 32 patients with acute myeloid leukemia undergoing combination therapy including either conventional (100 mg/m2 daily) or high-dose (1.0 or 3.0 g/m2 twice daily) AraC. Plasma AraC concentration showed a linear relationship to the applied AraC dose but did not correlate with intracellular AraCTP levels. During conventional-dose AraC therapy little interpatient variation was observed in AraCTP retention times in leukemic blasts from 5 patients with t1/2 values ranging from 1.70 to 2.50 h (median 2.14 h). In all cases AraCTP levels declined rapidly after the end of the AraC infusion. Substantial differences in AraCTP retention times were revealed, however, during 3 h infusions of either 1.0 or 3.0 g/m2 AraC in leukemic blasts from 10 patients with t1/2 values between 1.60 to 7.63 h (median 2.42 h). In addition, AraCTP levels declined in only one patient by > 10% within the first hour after the end of therapy and remained constant or even increased up to 1.5-fold in a post treatment period of 1 to 2.5 h in the other nine cases. In contrast, AraCTP retention times were relatively uniform in normal mononuclear blood cells from 11 patients with t1/2 values of 3.34 to 5.29 h (median 3.85 h). More importantly, AraCTP levels dropped by > 10% within the first hour after the end of the high dose AraC infusion in eight of 11 cases. A post-therapeutic increase > 10% was not observed in any patient. Similar findings emerged after in vitro exposure of normal bone marrow cells from six healthy volunteers to 20 mumol/l AraC for 3 h revealing a > 10% decrease of intracellular AraCTP within the first post treatment hour in all cases with AraCTP retention times of 2.29 to 8.63 h (median 3.20 h). These differences in AraCTP pharmacokinetics between leukemic and normal blood cells may provide the basis for a modified timing of AraC administration with the aim of selectively maintaining cytotoxic AraCTP levels in leukemic blasts while allowing an intermittent drop of AraCTP levels in normal cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1453773 TI - A retinoid acid 'resistant' t(15;17) acute promyelocytic leukemia cell line: isolation, morphological, immunological, and molecular features. AB - We report the isolation of a maturation-resistant acute promyelocytic leukemia (APL) cell line. This permanent cell line, derived from the same patient as the maturation inducible NB4 cell line, is the first retinoid-resistant cell line with a t(15;17) chromosomal translocation. Morphological, immunocytochemical and molecular features of the maturation responsive (NB4) and unresponsive (NB4-RAr) cells are compared. The isolation of the NB4-RAr cell line occurred through a two step process requiring the continuous selective pressure of all-trans-retinoic acid. Cells are also resistant to 13-cis-retinoic acid. Karyotypic and Southern blot analyses show that the two cell lines are similar with respect to the translocation. Northern-blot analyses show that the chimeric fusion transcript PML-RAR alpha and the normal allelic PML and RAR alpha transcripts are similarly expressed in both cell lines. The molecular basis for unresponsiveness to retinoic acid is not known. This resistant cell line offers a cellular model for molecular biology studies on the mechanism of induction of APL cell maturation, as well as a means to elucidate the molecular mechanisms of resistance. It also furnishes a unique tool for designing and/or screening new therapeutic drugs to avoid or relieve retinoid maturation blockage. PMID- 1453774 TI - Absence of negative growth regulation in three new murine radiation-induced myeloid leukemia cell lines with deletion of chromosome 2. AB - Murine radiation-induced acute myeloid leukemia (RI-AML) may be considered as the experimental counterpart of human secondary leukemia. Three new myelomonocytic cell lines derived from RI-AML and carrying a partially deleted chromosome 2 are described. The RI-AML cells responded with increased proliferation after being incubated with the hemopoietic growth factors rG-CSF, rGM-CSF and IL-3. Increased proliferation of the same extent without any effect in differentiation, was also demonstrated in the RI-AML cells after incubation with IL-6 and with mouse lung conditioned medium (CM) and Krebs ascites tumor cells CM which induce differentiation in normal and most leukemic myeloid cells. Down-regulation of the c-myc gene and induction of (2'-5') oligo-adenylate synthetase (reflecting autocrine interferon secretion), two essential mechanisms operating during arrest of growth and concomitant differentiation, were demonstrated to be absent in RI AML cells. In contrast, the M1 cells responded to the above differentiating factors with growth arrest and differentiation and with appropriate c-myc down regulation and synthetase induction. The genetic basis for the distinct RI-AML cells' behavior may be connected with the loss or structural and/or functional abnormalities of DNA sequences located in the deleted part of chromosome 2 or in the respective allele. The presently described new RI-AML cell lines may be used for studies concerning myeloid leukemogenesis in general and secondary leukemia in particular. PMID- 1453775 TI - P53 mutations in myelodysplastic syndromes. AB - Point mutations in the p53 tumor-suppressor gene are the most frequently identified genetic alterations in human malignancies. In order to evaluate the role of p53 mutations in the multistep process of leukemogenesis we studied 61 patients with myelodysplastic syndromes using single-strand conformation polymorphism analysis of polymerase chain reaction products as well as direct sequencing. Mutant alleles were observed in 1/14 refractory anemia with excess of blasts (RAEB) and 2/5 RAEB in transformation. The three mutations represented G:C to A:T transitions at codon 141 (exon 5) and codons 245 and 248 (exon 7), respectively. These data suggest that p53 mutations may contribute, albeit rarely, to the development of preleukemic disorders of the myeloid cell lineage. PMID- 1453776 TI - Leukaemia Research Fund (UK) international research symposium: new approaches to the study of leukaemogenesis. PMID- 1453778 TI - Impedance changes during the compound nerve action potential: implications for impedance imaging of neuronal depolarisation in the brain. AB - Impedance changes were measured during the compound action potential (CAP) in isolated crab nerves with 50 kHz or direct applied current (DC), to suggest an optimal frequency for the imaging of neuronal depolarisation by electrical impedance tomography (EIT). With DC, a predominant apparent impedance decrease of 0.2-0.7 per cent of the resting baseline was observed, which had a time course similar to that of the action potential. Control recordings suggested that these changes could not be attributed to technical errors resulting from the measurement method. A component in some measurements was attributable to effects of the measuring current on the latency of the CAP, but the mechanism underlying the remainder of the changes was unclear. No changes greater than +/- 0.005 per cent were seen with measurement at 50 kHz. This suggests that research into noninvasive rapid imaging of nervous activity in the brain with EIT would be more profitably performed with measurements at frequencies lower than the 50 kHz currently used for safety reasons. PMID- 1453777 TI - The need for standards in recording and analysing respiratory sounds. AB - Respiratory sounds (RSs) recorded from the chest and trachea are nowadays being electronically analysed by many investigators with a view to (i) determining the mechanisms of their production, and (ii) to develop automated diagnostic systems based on RS analysis, that objectively categorise RS as being associated with health or respiratory diseases. However, one problem that hampers this type of research is that almost every RS investigation team uses different equipment, protocols and analysis methods which, to varying degrees, makes inter investigator results difficult to compare. The review first discusses the many variables involved in RS recording and analysis, and the different approaches used by different investigators, to highlight this problem and its consequences. Secondly, although the review cannot propose immediately acceptable guidelines and standards for RS analysis, it proposes a 'seed' set of guidelines that are 'up for discussion' between investigators in the field, the final goal being to inject a degree of standardisation in equipment and methods that are acceptable to all involved. PMID- 1453779 TI - Noninvasive acoustical detection of coronary artery disease using the adaptive line enhancer method. AB - Previous studies have indicated that heart sounds may contain information which is useful in the detection of occluded coronary arteries. Specifically, previous work based on analysing heart sounds recorded during the diastolic portion of the cardiac cycle, when blood flow through the coronary arteries is maximum, has shown that additional frequency components are present in patients with coronary artery disease. To further explore the application of advanced signal processing techniques to the noninvasive detection of coronary artery disease, a new signal processing approach is presented using adaptive line enhancing (ALE) and spectral estimation of diastolic heart sounds taken from recordings made at the patient's bedside. This approach comprises two cascaded processes. In the first the ALE method is used to enhance the diastolic heart sounds and eliminate background noise. In the second process, either autoregressive (AR) or autoregressive moving average (ARMA) spectral methods are used to estimate the model parameters. Model parameters (the power spectral density (PSD) functions and the poles of the AR or ARMA method) were used to diagnose patients as diseased or normal. Results showed that normal and abnormal recordings were correctly identified in 39 of 43 cases using the new method. These results also confirm that high-frequency energy above 400 Hz is associated with coronary stenosis. PMID- 1453780 TI - Heart rate and body temperature sensitive diaphragm pacing. AB - Two ways of rate control for diaphragm pacing are proposed. One is rate control using only the patients' body temperature (method I). The other is rate control by both the patients' heart rate and body temperature (method II). To test the effectiveness of these methods, a diaphragm pacemaker which can be controlled by both heart rate and body temperature has been developed. It was applied to nine mongrel dogs. The pacing rate is controlled by atrial blood temperature (method I) or by both heart rate and temperature (method II). The animal's metabolism was elevated by the administration of a pyrogenic drug. It was found that method I is not suited to rapid changes in metabolism; however, it is useful in extreme metabolic elevation. An animal's metabolism was supported by using method II in all ranges of metabolism. This method proved more effective than method I for rate-responsive diaphragm pacing. PMID- 1453781 TI - Closed-chest cardiac stimulation with a pulsed magnetic field. AB - Magnetic stimulators, used medically, generate intense rapidly changing magnetic fields, capable of stimulating nerves. Advanced magnetic resonance imaging systems employ stronger and more rapidly changing gradient fields than those used previously. The risk of provoking cardiac arrhythmias by these new devices is of concern. In the paper, the threshold for cardiac stimulation by an externally applied magnetic field is determined for 11 anaesthetised dogs. Two coplanar coils provide the pulsed magnetic field. An average energy of approximately 12 kJ is required to achieve closed-chest magnetically induced ectopic beats in the 17 26 kg dogs. The mean peak induced electric field for threshold stimulation is 213 V m-1 for a 571 microseconds damped sine wave pulse. Accounting for waveform efficacy and extrapolating to long-duration pulses, a threshold induced electric field strength of approximately 30 V m-1 for the rectangular pulse is predicted. It is now possible to establish the margin of safety for devices that use pulsed magnetic fields and to design therapeutic devices employing magnetic fields to stimulate the heart. PMID- 1453782 TI - Component wave delineation of ECG by filtering in the Fourier domain. AB - A complete solution to the fundamental problem of delineation of an ECG signal into its component waves by filtering the discrete Fourier transform of the signal is presented. The set of samples in a component wave is transformed into a complex sequence with a distinct frequency band. The filter characteristics are determined from the time signal itself. Multiplication of the transformed signal with a complex sinusoidal function allows the use of a bank of low-pass filters for the delineation of all component waves. Data from about 300 beats have been analysed and the results are highly satisfactory both qualitatively and quantitatively. PMID- 1453783 TI - The effect of averaging cardiac Doppler spectrograms on the reduction of their amplitude variability. AB - The effect of averaging cardiac Doppler spectrograms on the reduction of their amplitude variability was investigated in 30 patients. Beat-to-beat variations in the amplitude of Doppler spectrograms were also analysed. The quantification of amplitude variability was based on the computation of the area under the absolute value of the derivative function of each spectrum composing mean spectrograms. Fast Fourier transform using a Hanning window was used to compute Doppler spectra. Results obtained over systolic and diastolic periods showed that the reduction of amplitude variability followed an exponentially decreasing curve characterised by the equation f (r) = 100 e-beta(r-1), where r is the number of cardiac cycles, beta the exponentially decreasing rate, and 100 the normalised variability for r = 1. In systole, the decreasing rate beta was 0.165, whereas in diastole it was 0.225. Reductions of the variability in systole for a number of cardiac cycles of 5, 10, 15, and 20 were 48, 77, 90 and 96 per cent, respectively. In diastole, reductions of the variability for the same numbers of cardiac cycles were 59, 87, 96 and 99 per cent, respectively. Based on these results, it can be concluded that no significant improvement in the reduction of amplitude variability may be obtained by averaging more than 20 cardiac cycles. PMID- 1453784 TI - Six-band sub-band coder on ECG waveforms. AB - An ECG sampled at a rate of 500 samples s-1 or more produces a large amount of redundant data that are difficult to store and transmit. A process is therefore required to represent the signals with clinically acceptable fidelity and with the least code bits possible. In the paper, an efficient sub-band coding method for encoding ECG waveforms is presented. Although sub-band coding has been successfully applied to speech signals, it is the first time that this technique has been applied to the encoding of ECG waveforms. A frequency band decomposition of an ECG waveform is carried out by means of quadrature mirror filters (QMF), which split the ECG spectrum into six bands of unequal width. In the lower frequency bands, which contain most of the ECG spectrum energy, a larger number of bits per sample is used, whereas in upper frequency bands, which contain noise like signals, fewer bits per sample and the run length coding method are used. The simulation results are presented in terms of bit rates and the quality of the reconstructed waveforms. The results show that a reproduction with an average signal-to-noise ratio (SNR) of 29.97 dB can be achieved even at an average bit rate of 0.81 bits per sample. PMID- 1453785 TI - Comparison between the more recent techniques for smoothing and derivative assessment in biomechanics. AB - When analysing and evaluating human motion, two strictly interconnected problems arise: the data smoothing and the determination of velocities and accelerations from displacement data. Differentiating procedures magnify the noise superimposed on the useful kinematic data. A smoothing procedure is thus required to reduce the measurement noise before the differentiation can be carried out. In the paper two techniques for derivative assessment are presented, tested and compared. One of these is the procedure known as one of the best automatic smoothing and differentiating techniques: generalised cross validatory spline smoothing and differentiation (GCVC). The other, which has recently been presented, features an automatic model-based bandwidth-selection procedure (LAMBDA). The procedures have been tested with signals presented by other authors and available in the literature, by test signals acquired using the ELITE motion analyser and by synthetic data. The results show better or similar performance of LAMBDA compared with GCVC. In the cases in which the natural conditions at the signal boundaries are not met GCVC gives bad results (especially on the third derivative) whereas LAMBDA is not affected at all. Moreover, analysis time is dramatically lower for LAMBDA. PMID- 1453786 TI - On/off control in FES-induced standing up: a model study and experiments. AB - Control of paraplegic standing up was studied with respect to the limitation of the end-velocity of the knee joint when the patient reaches the upright position. Closed-loop on/off control of knee extensor muscle was compared with open-loop controlled standing up both in a model study and in paraplegic patients in a controlled model situation. Criteria were knee-end-velocity and knee extensor muscle activation time. Sensitivity of the system to additional arm support and (in the model study) to the dynamics of knee extensor muscle was studied. It is concluded that the control scheme may reduce knee-end velocity to about 40 per cent and knee extensor activation time to near 70 per cent of the respective open loop values. PMID- 1453788 TI - Vectorial measurement of blood velocity by means of ultrasound. AB - The complete determination of blood velocity as a vector can be achieved using ultrasound techniques, by correlating the echo signals provided by a sector transducer. Here the general problem is approached by suggesting the processing procedure which should be adopted, so that longitudinal and transverse velocity components can be separated. After this a specific transducer layout is considered, which is suitable for in-plane measurements, and possible performances are evaluated by means of simulation. Finally, an experimental facility, set up to demonstrate the validity of the theoretical lines developed in two-dimensional geometry, is described, together with the preliminary results obtained. PMID- 1453787 TI - FFT-based digital tactile vocoder system for real-time use. AB - A microprocessor-based real-time digital vibrotactile vocoder system has been developed to train the deaf and for artificial hearing research. The system is composed of a microcomputer module with a digital signal processor, interface units and an attenuator/driver circuit. Live or digitised (stored or synthetic) speech is presented to the skin spectrally through a belt housing eight or 16 vibrators. Speech is processed in real time using a fast Fourier transform. The system is also capable of presenting any arbitrary spatiotemporal pattern on the skin for artificial hearing experiments. A preliminary experiment with a deaf subject indicates that the system is potentially an effective device for artificial hearing. PMID- 1453789 TI - Radio frequency probe and power amplifier for nuclear magnetic resonance microscopy and microvolume selected 1H spectroscopy at 500 MHz. PMID- 1453790 TI - Semi-automated system for photographing wing motion in free-flying insects. PMID- 1453791 TI - Theoretical and experimental study of wound healing: application to leg ulcers. PMID- 1453792 TI - Three-dimensional microprocessor-controlled electrode positioning system for microelectrode measurement. PMID- 1453793 TI - Micropower, strain-gauge sampling circuit for prosthetic limb applications. PMID- 1453794 TI - Miniature, remotely-controlled microelectrode driver for use in conscious, unrestrained animals. PMID- 1453795 TI - Top of R-wave trigger circuit. PMID- 1453796 TI - High-pass filtering of ECG signals using QRS elimination. PMID- 1453797 TI - Treatment of chronic wounds by means of electric and electromagnetic fields. Part 1. Literature review. AB - The healing of a cutaneous wound is accompanied by endogeneous electrical phenomena. Not knowing whether they represent merely a side-effect of the physiological processes which take course during healing or whether they play a much more important role as mediators of healing, externally applied electricity was examined as a therapeutic tool for the enhancement of natural regenerative processes. In the present review a historical literature survey dealing with human applications of electric current for wound healing acceleration is given. It presents a complete palette of heterogeneous studies, differing in the parameters of applied electric current, in delivery modes as well as in the types of wounds being stimulated. Because of all these differences, comparing the efficacy of the described methods is difficult and could hardly be objective. Therefore greater stress was laid upon the discussion concerning the problems in designing clinical studies (size of the sample observed, control group, ethics of the procedures), rationales for the employment and possible underlying mechanisms of particular methods, and problems of evaluating their efficacy. In spite of the extensive work performed in the field of electrical wound healing we remain only part way towards explaining the mechanisms by which electricity reinforces the regenerative capabilities of injured tissue as well as only part way towards the selection of the optimal stimulation method from among the published reports. PMID- 1453798 TI - Effect of ensemble averaging on amplitude and feature variabilities of Doppler spectrograms recorded in the lower limb arteries. AB - The objective of the present study was to analyse the effect of averaging Doppler blood flow signals in lower limb arteries on amplitude and feature variabilities. Doppler signals recorded in 41 iliac and 35 superficial femoral arteries having different categories of stenosis were averaged over 1-15 cardiac cycles. Based on the relative decreasing rate of an index of variability, results indicated that amplitude variability of the spectrograms was exponentially reduced to 30, 6 and 1 per cent when averaging five, ten and 15 cardiac cycles, respectively. Nine diagnostic features were extracted from Doppler spectrograms and their variations from one cardiac cycle to the next quantified. Based on the relative decreasing rate of these variations, results indicated that feature variability was exponentially reduced to 30, 4 and 1 per cent when averaging five, ten and 15 cardiac cycles, respectively. The effect of averaging on the discriminant power of the features to separate the different categories of stenosis was also investigated by performing t-test analyses. Results showed that averaging between five and ten cardiac cycles provided the better discriminant power for most cases, whereas averaging over more than ten cardiac cycles was of little benefit. Based on the spectral analysis technique used in the present study, we conclude that averaging over ten cardiac cycles is sufficient for the analysis of Doppler spectrograms recorded in the lower limbs. PMID- 1453799 TI - Frequency domain analysis of highly amplified ECG on the basis of maximum entropy spectral estimation. AB - Recognition of patients with high risk for ventricular tachycardia (VT) or sudden cardiac death is of high clinical importance. We have investigated the efficiency of maximum entropy spectral estimation (MES) to detect such risk patients on the basis of highly amplified surface ECG. In comparison with the traditionally applied periodogram (fast Fourier transform), the MES produces sharper and more pronounced peaks in the power density spectrum (PS). The main problem is the influence of residual noise (after averaging), which often leads to additional components in the PS. To completely avoid this negative noise influence we developed a new algorithm, called the variance subtraction method. In a first clinical investigation 86 per cent of patients with myocardial infarction and ventricular tachycardia have shown frequency components above 80 Hz in the PS compared with healthy persons where no frequency components above this 80 Hz level could be detected. PMID- 1453800 TI - Duchenne muscular dystrophy quantification: a multivariate analysis of surface EMG. AB - The paper describes a method of quantifying Duchenne muscular dystrophy which is examiner independent and uses surface electromyographic signals (EMG). A standardised protocol is proposed. Spectral parameters are first computed from digitised EMG, then a polynomial model is deduced from the evolution of each parameter. A discriminant analysis between healthy and DMD subjects leads to the determination of a discriminant plane and a level of sickness index. PMID- 1453801 TI - Propagation model using the DiFrancesco-Noble equations. Comparison to reported experimental results. AB - Propagation, re-entry and the effects of stimuli within the conduction system can be studied effectively with computer models when the pertinent membrane properties can be represented accurately in mathematical form. To date, no membrane models have been shown to be accurate representations during repolarisation and recovery of excitability, although for the Purkinje membrane the DiFrancesco-Noble (DN) model has become a possibility. The paper examines the DN model, restates its equations and compares simulated waveforms in a number of propagation contexts to experimental measurements reported in the literature. The objective is to determine whether or not the DN model reproduced phenomena such as supernormality, shortening in action potential duration during pacing rate increases, alternation of duration with changes in rhythm, graded responses and 'all-or-none' repolarisation in a quantitatively realistic way, as each of these come from time and space dependencies not directly a part of the ionic current measurements on which the DN model is based. The results show that the DN equations correctly simulate these situations and support the goal of having a model that is broadly applicable to Purkinje tissue, including refractory period properties and response to electrical stimulation. PMID- 1453802 TI - Potential distribution and single-fibre action potentials in a radially bounded muscle model. AB - In modelling the electrical behaviour of muscle tissue, we used to employ a frequency-dependent volume conductor network model, which was infinitely extended in all directions. Equations in this model could be solved using a finite difference approach. The most important restriction of this model was the fact that no boundary effects could be incorporated. Analytical models of muscle tissue normally do not have this disadvantage, but in those models the microscopic structure of muscle tissue cannot be taken into account. In the paper, we present a combined numerical/analytical approach, which enables the study of potential distributions and SFAPs in simulated microscopic muscle tissue in which the influence of the muscle boundary has been considered. We considered muscle models with radii of 1.5 mm and 10 mm. Both models were compared with an unbounded network model. In the model with a radius of 1.5 mm we varied the position of the active fibre relative to the muscle surface. It appeared that in most cases the presence of a boundary had a considerable effect on the potential distribution. An increase in the peak-to-peak value of the SFAP amplitude up to 300 per cent was noticed when the active fibre was positioned 500 microns beneath the muscle surface in a model with a radius of 1.5 mm. PMID- 1453803 TI - Mathematical modelling of flow distribution in the human cardiovascular system. AB - The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes. PMID- 1453804 TI - Cardiovascular responses to external counterpulsation: a computer simulation. AB - A mathematical model of the human cardiovascular system is presented which includes a simulation of cardiac assistance by external counterpulsation. The model was established to study the effects of external counterpulsation on cardiovascular haemodynamics. The closed simulation includes both the left and the right heart and the pulmonary circulation. The model is able to provide data for the behaviour of the system under varying modes of assistance. Our results suggest that control of external counterpulsation is more difficult than control of the intra-aortic balloon pump and requires regulation of a larger number of variables. The results also suggest that a tradeoff exists between improved oxygen delivery to the heart and reduction in the oxygen consumption of the myocardium, an observation similar to that reported for the intra-aortic balloon pump. PMID- 1453805 TI - Equivalent dipole estimation of spontaneous EEG alpha activity: two-moving dipole approach. AB - A method of estimating equivalent moving and fixed dipoles from the scalp recorded EEG alpha waves, with the realistic geometry of the head taken into account, is presented. Twenty-one silver electrodes were used to collect spontaneous EEG alpha waves on the scale. Four models, the single-moving dipole model, the single-fixed dipole model, the two-moving dipole model and the two fixed dipole model were applied to approximate the EEG alpha field on the scalp. The algorithm, based on a least-squares fit for estimating the moving and the fixed dipoles by using a realistically shaped head model, is described. The numerical accuracy of the algorithm is also evaluated by a computer simulation. It is found that the spontaneous EEG alpha activity observed on the scalp can be represented by two equivalent moving dipoles, simultaneously located separately in the occipital regions of the right and the left hemisphere, at a depth of 4-6 cm beneath the scalp, with a goodness-of-fit of up to 97 per cent for all subjects examined. The excellent fit of the two-moving dipole model to the EEG human alpha activity is also compared with the single-dipole fit. PMID- 1453806 TI - Droop: a rapidly computable descriptor of local minimum tissue temperature during conductive interstitial hyperthermia. AB - Although the goal of local hyperthermia therapy for cancer is to elevate the temperature of a tumour to cytotoxic levels, without the presence of 'cold spots', varying blood flow has made the achievement of consistent, therapeutic temperature distributions extraordinarily difficult. The paper presents a novel approach to estimating local minimum tumour temperatures during conductive interstitial hyperthermia which facilitates identification and elimination of cold spots. Conductive interstitial hyperthermia is modelled mathematically for a parallel array of implanted, electrically heated catheters which warms the treated tissue by thermal conduction and blood perfusion. Computer simulations employing the bioheat transfer equation reveal a predictive relationship between implanted catheter temperature, catheter power, implantation geometry and local minimum tumour temperature. Formulation of this relationship in terms of a parameter named 'droop' allows estimation of local minimum intratumoural temperatures from individual catheter temperature and power. Computer simulations are also performed to determine the sensitivity of the droop-based estimator to variations in properties of the tissue and catheters. Generally, variations in geometry or thermal properties of about 10 per cent cause estimation errors of less than 1 degree C in magnitude. These results suggest that online estimates of thermal 'droop' may provide a practical route to more consistent control of intratumoural minimum temperature during conductive interstitial heat therapy. PMID- 1453807 TI - Semiautomatic three-dimensional knee motion assessment system. AB - A semiautomatic three-dimensional knee motion assessment system has been developed based on an optoelectric motion tracking system connected to an IBM compatible computer. Critical decisions made in implementing the software component of the system include the modelling of the thigh and lower leg segments, calculating the knee angles, reaction forces, and moments; the file structure used and the format of the programs used to process the data are outlined. Once the subject-specific data have been collected, the system of programs requires no other user-intervention during processing. Also, selected curve parameters are automatically extracted from the output and combined with the subject-specific data that include precision X-ray and anthropometric data, which are all added to a knee motion assessment database. The automated portion of the system frees the experimenter from data processing and allows concentration on data analysis. PMID- 1453808 TI - Approach to the estimation of alveolar pressure from noninvasive measurement of upper airway resistance. AB - An alternative to whole body plethysmography is proposed for estimating upper airway resistance. The feasibility study indicates that the method should be suitable for diagnostic and clinical purposes, following a proper survey and the testing of its reproducibility. 11 subjects are asked to breath normally through 12 small resistances while flow and pressure are monitored at the mouth. Chest movements are recorded by sampling a chest cross-section, and relative variations of the cross-section are compared to the expired and inspired volumes. No viscoelastic effects are significantly documented so that in a first approximation a model consisting only of resistors is applied to the airways. In each subject the patterns of the flow and mouth-pressure are heuristically estimated as a polynomial function of the added resistance. From the fit of the resistor model, the internal resistance of the airways is estimated as that value able to link the flow-resistance function to the pressure-resistance function, according to the classic Kirchhoff laws. We obtain resistances of (mean resistance +/- SD) 2.9 +/- 1.1, range 1.1 to 5.2, hPasdm-3 during expiration and 2.5 +/- 0.8, range 1.3 to 3.7, hPasdm-3 during inspiration. PMID- 1453809 TI - Radial changes of extracellular potential amplitude and integral characteristics and the inverse problem in electroneurography. AB - The possibility of solving the inverse problem in electroneurography, i.e. of estimating the main parameters specifying the activated fibre's functional state, using the amplitude and integral characteristics of the surface potentials generated by infinite homogeneous fibres, has been analysed. An analytical expression has been found for the amplitude of the negative phase Anph of the single fibre extracellular action potential (SFEAP) as a function of the wavelength b, the fibre-electrode distance y and a scale factor Ao proportional to the intracellular action potential amplitude Vm, to the square of the fibre radius a and to the ratio of the axoplasm conductivity sigma a and volume conductor conductivity sigma e. For a large fibre-electrode distance, typical of surface recordings, an analytical expression of the integral of the negative phase Inph of the SFEAP as a function of Ao, b, y and the propagation velocity v was also found. Simple methods are proposed for estimating v, the location of the electrical centre of the activated fibres' territory and the product of the number of activated fibres N, duration T(in) of the intracellular action potential and of the factor Ao. The estimation errors due to the temporal and spatial dispersion of the activated fibres were analysed as a function of the fibre-electrode distance and the territory shape. PMID- 1453810 TI - Three-wheel cycle ergometer for use by men and women with paralysis. PMID- 1453811 TI - Transcutaneous optical telemetry system for an implantable electrical ventricular heart assist device. PMID- 1453812 TI - Flexible PC-based workstation for auditory evoked potential and psychoacoustic experiments. PMID- 1453813 TI - Effect of the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) on the incidence of invasive cervical cancer. AB - The Clinical Laboratory Improvement Act of 1988 (CLIA '88) mandates strict, new quality-control measures for laboratories that interpret cervical cytology smears. Proposed regulations include proficiency testing of cytotechnologists and remediation for technologists and laboratories that fail to meet proposed proficiency standards. Proponents of the new regulations argue that these measures will reduce deaths from cervical cancer by reducing the false-negative rate of the Papanicolaou (Pap) test, but opponents argue that the regulations will increase the price of processing Pap tests and thereby reduce access to cervical cancer screening for high-risk, vulnerable populations. To examine these claims the authors used David Eddy's published simulation to model the natural history and detection of cervical neoplasia, and developed a new model to examine the health consequences of diminished access to Pap testing. The authors estimated the false-negative rate of the Pap test and the price elasticity of demand for preventive services on the basis of the published literature, and modeled the entire range of published or quoted predictions about the impact of CLIA '88 on accuracy and price. The results show that, if effects on access are ignored, reducing the false-negative rate from 15% to 5% would prevent 66 invasive cancers per 100,000 average risk women screened. However, under moderate assumptions regarding the effect of price on access, the regulations would prevent only 11 (instead of 66) cancers per 100,000 eligible women. The regulatory effect is very sensitive to the degree of improvement in the false negative rate and increase in price that the regulations cause. Over the range of assumptions and predictions encountered in the literature and tested in our analysis, the proposed regulations could greatly reduce or greatly increase the incidence of invasive cancer, especially among high-risk and uninsured women. The implementation of the regulations should be delayed until new information regarding the actual false-negative rate of the Pap test allow a more precise estimate of the potential impact on the incidence of cervical cancer. PMID- 1453814 TI - Variation in a medical faculty's decisions to transfuse. Implications for modifying blood product utilization. AB - Previous studies have identified disconcerting differences in transfusion practices among physicians. This article investigates decisionmaking on transfusion by a medical school faculty. One hundred fourteen physicians indicated their propensity to transfuse 24 hypothetical patients who varied systematically in four clinical cues. Physicians agreed with transfusion for a widely divergent number of these patients (mean, 14.6; standard deviation, 5.5; range, 0 to 24). Although the physicians agreed on the order of importance of the clinical cues, they varied significantly in the importance they empirically attributed to the cues and in their thresholds for transfusion. Aside from a slightly higher propensity to transfuse by general internists, differences in decisionmaking were not attributable to physician-based variables. The wide variability in decisionmaking among physicians in the face of agreement on the order of importance of clinical cues suggests that quality assurance programs, and guidelines that only list the cues that ought to influence transfusion decisions, have low potential to achieve blood-product conservation. PMID- 1453815 TI - A discrete choice model of alcoholism treatment location. AB - In this study, a discrete choice model of alcoholism treatment location, with special emphasis on the roles of comorbidities is considered. Three specific questions are addressed: 1) what demographic and health factors have significant impacts on treatment location for both short- and long-term alcoholism and nonalcoholism treatments?; 2) how does the impact of alcohol dependence differ from the impact of alcohol abuse, on probabilities of short-term or long-term inpatient treatment?; and 3) what are the impacts of health comorbidities on probabilities of inpatient treatment in the short or long term? A binomial logit model is estimated for short- and long-term alcoholism treatment, as well as for short- and long-term nonalcoholism treatment (which occurs at the same time). The results indicate the importance of comorbidities in predicting treatment location. They also indicate a trend during the 1980s toward increased use of outpatient rather than inpatient treatment. PMID- 1453817 TI - Development and validation of the Nursing Severity Index. A new method for measuring severity of illness using nursing diagnoses. Nurses of University Hospitals of Cleveland. AB - The purpose of this study was to develop and validate the Nursing Severity Index, a new method used to measure the admission severity of illness of hospital patients using nursing diagnoses, which categorize biologic, functional, cognitive, and psychosocial abnormalities. This retrospective cohort study with independent development and testing phases was conducted at a U.S. academic medical center. In the development phase, data regarding 14,183 adult medical surgical patients admitted to the medical center in 1985 and 1986 was used. In the testing phase, data regarding 7,302 patients admitted in 1987 and 1988 was used. Primary nurses prospectively recorded the presence or absence of 61 nursing diagnoses on admission. Demographic and clinical data were obtained from hospital data bases. In the development phase, the number of admission nursing diagnoses was highly related (P < 0.001) to in-hospital mortality. Using multiple logistic regression, 34 nursing diagnoses were identified as independent predictors of mortality; the Nursing Severity Index equals the number of these 34 diagnoses. In the testing phase of 7,302 patients, the Nursing Severity Index was related (P < 0.001) to mortality rates, which were 0.5%, 1%, 2%, 6%, 13%, 22%, and 31% in seven hierarchical strata defined by the Index. The Index was as accurate in predicting mortality as MedisGroups (receiver-operating-characteristic curve areas, 0.814 +/- 0.016 vs. 0.845 +/- 0.015, respectively, P = 0.12). Furthermore, the Nursing Severity Index and MedisGroups together (receiver operating characteristic curve area 0.880 +/- 0.014), were more accurate (P < 0.01) than either measure alone. The Nursing Severity Index assesses multiple dimensions of illness, can be easily measured during routine patient care, accurately predicts the risk of in-hospital death, and has similar prognostic accuracy as MedisGroups. Its usefulness in outcomes assessment, quality assurance, and case management merits further study. PMID- 1453816 TI - Development of the 'Activities of Daily Vision Scale'. A measure of visual functional status. AB - To develop a method for the evaluation of visual function in subjects with cataracts, the authors identified 20 visual activities and categorized them into five subscales (distance vision, near vision, glare disability, night driving, and daytime driving) that comprised the Activities of Daily Vision Scale (ADVS). Each subscale in the ADVS was scored between 100 (no visual difficulty) and 0 (inability to perform the activity because of visual difficulty). In 334 subjects scheduled for cataract extraction (mean age 75 +/- 9 years, 67% women), ADVS scores (mean +/- standard deviation) for each subscale ranged from 44 +/- 31 for night driving to 72 +/- 24 for near vision activities. When administered by telephone, inter-rater reliability coefficients (r) were 0.82 to 0.97 (P < 0.001) for each of the subscales, and test-retest reliability was 0.87 for the scale overall. Cronbach's coefficient alpha was very high for both the in-person (alpha = 0.94) and telephone (alpha = 0.91) formats. Criterion validity, the correlation between visual loss and ADVS score, was -0.37 (P < 0.001) when the ADVS was administered in person and -0.39 (P < 0.001) when it was administered by telephone. Content validity as assessed with factor analysis showed that 88% of the variance of the principal components weighted on one factor. The authors conclude that substantial visual disability is not captured by routine visual testing and that the ADVS is a reliable and valid measure of patient's perception of visual functional impairment. PMID- 1453818 TI - A receiver operating characteristic (ROC) curve analysis of a model of mental health services use by Puerto Rican poor. AB - In this study, the contribution of four distinct domains of the Help Seeking Decision Making model to predicting the use of mental health services is examined. Using a proposed methodology the authors assess the relevance of this model and its domains to mental services planning. The methodology combines logistic regression analysis and receiver operating characteristic (ROC) curves. Logistic regression analysis allows us to examine the individual variables of the model and generate predictions about use. ROC curves allow us to compare and interpret the relative contribution of a predisposing domain, a physical and mental health domain, an enabling-restrictive domain, and an organizational domain in correctly classifying users and nonusers of mental health services. The physical and mental health domain yielded a Somer's D-statistic of 0.7, which corresponds to an 85% correct classification of randomly selected pairs of users and nonusers. The study findings suggest that comparing ROC curves helps to describe and interpret the domains of the model that are relevant for making predictions about who will or will not use mental health services during a 1-year period. PMID- 1453819 TI - The relationship between commuting patterns and health resources in nonmetropolitan counties of the United States. PMID- 1453820 TI - [Parotiditis in postvaccination period. Epidemiologic pattern and vaccine effectiveness in an epidemic outbreak]. AB - BACKGROUND: Upon the detection of an excess number of cases of parotiditis in La Almolda (Zaragoza) a descriptive study of the epidemic was carried out with vaccination efficacy being quantified. METHODS: The definition and system of detection of the cases was established. To calculate the rate of infection the available demographic data were used as denominators. A study of retrospective groups was designed to calculate the vaccination efficacy including one group of vaccinated subjects and another of non vaccinated subjects. Age and viral contact were considered as inclusion criteria. RESULTS: Fifty-two cases of parotiditis were detected. The rate of infection in a population of under 30 years of age was 18.9%. The most affected age group corresponded to the interval of between 10-14 years of age with a specific rate of 46.5%. The risk of infection was greatest amongst public school students (RR = 5; p = 0.00015). Vaccination efficacy was 74.68%. CONCLUSIONS: This study confirms the tendency that parotiditis affects older subjects during the prevaccination period. The vaccination efficacy found to be 74.68% was lower the efficacy determined from seroconversion studies. PMID- 1453821 TI - [Molecular analysis of chronic Philadelphia chromosome negative myeloid leukemia: study of 6 cases]. AB - BACKGROUND: Patients with Philadelphia negative (Ph-) chronic myeloid leukemia (CML) constitute a small proportion of the total number of patients with CML. Molecular analysis of these cases has permitted recognition that some cases present a breakpoint in the bcr region of chromosome 22, that is, the alteration constituting the substrate of the Ph chromosome. To date, the number of patients analyzed to this regard is low. METHODS: Six patients with Ph negative CML who constituted part of a series of 96 patients diagnosed with CML over a period of 6 years were studied. Analysis of the BCR gene in the DNA of the leuko-concentrate of peripheral blood was carried out with the Southern Blot technique, using the 3' and 5' probes and Transprobe and the restriction enzymes Bgl II, Eco RI, Hind III and Bam HI. The principal clinical-hematological characteristics of the patients were analyzed. RESULTS: Breakpoints were observed in the bcr region of chromosome 22 in 3 of the 6 patients, all of whom presented typical CML clinical hematological features. CONCLUSIONS: Half of the patients with Philadelphia negative (Ph-) chronic myeloid leukemia (CML) have a breakpoint in the bcr region of chromosome 22, a similar molecular pattern to the Ph positive CML and their clinical-hematological profile is indistinguishable from those with CML. PMID- 1453822 TI - [Drug consumption in diabetes mellitus (I). Estimate of the therapeutic profile and the prevalence in the regions of Tarragona (548,900 inhabitants). Grup per a l'Estudi de la Diabetis a Tarragona]. AB - BACKGROUND: This study was carried out to estimate the treatment characteristics and prevalence of diabetes mellitus (DM) diagnosed in the counties of Tarragona (548,900 inhabitants) from the consumption of hypoglycemic medication. METHODS: A stratified aleatory sample was made of the prescription of oral hypoglycemic agents (OHA) and insulin (INS) in 14 centers of primary health care. Calculation of pharmacy dispensing and prescriptions (computer network of the Institut Catala de la Salut) was carried out with a relation of the mean doses of the survey and the estimate of the consumer population being made. A contrast was made of the system with the daily doses defined (DDD/1,000 inhabitants/day) of the different OHA and INS preparations. RESULTS: Following aleatorization a representative sample of 550 diabetics, 64 (11.6%) type I and 486 (88.4%) type II was obtained. In total, 61 were treated with diet alone (IC 95%; 8-13%, p less than 0.05); 249 (41-49%) with OHA (51% of type II) and 240 (39-47%) received insulin, all the type I and 176 (36%) type II. In 23 cases (2-5%) multiple therapy with different drugs was confirmed and 72 (10-15%) were treated with the maximal doses of OHA recommended. The rate of OHA/INS was 2.02-2.05. The prevalence of pharmaco treated DM was 1.9% (prescriptions of public health) and 2.1-2.3% (total consumption). The method for DDD was evaluated as between 1.8% (prescriptions) and 2.0% (total consumption). Globally, during 1990 the prevalence of DM diagnosed in Tarragona was estimated as between 2.1-2.5%. CONCLUSIONS: The estimation of the prevalence of diabetes mellitus indicated higher numbers than those obtained in other studies providing a first line indicator for the planning of care for diabetics in this demarcation. The study also identified the real therapeutic tendencies permitting the extraction of lines of action for the education of diabetics and the formation of professionals attending these patients. PMID- 1453823 TI - [Is parotiditis preventable in Spain]. PMID- 1453824 TI - [Hepatitis A. An eradicable disease?]. PMID- 1453825 TI - [Pharmaceutic promotion and publicity: quo vadis?]. PMID- 1453826 TI - [Future techniques of prenatal diagnosis (II). Fetal cells in blood of pregnant women]. PMID- 1453827 TI - [Lupus anticoagulant in patients infected by the human immunodeficiency syndrome in stages preceding the acquired immunodeficiency syndrome]. PMID- 1453828 TI - [Massive pericardial effusion and cardiac tamponade as presentation form of hypothyroidism]. PMID- 1453829 TI - [Hypoglycemic coma, infrequent cause of arrhythmia]. PMID- 1453830 TI - [Clinical usefulness of serum determination of antigen associated with esophageal carcinoma]. PMID- 1453831 TI - [Considerable hypoglycemia in anorexia nervosa]. PMID- 1453832 TI - [Focal neurologic manifestations in a patient with mediterranean boutonneuse fever]. PMID- 1453833 TI - [Leiomyoma of soft tissues and deep localization]. PMID- 1453834 TI - [LE cells in peripheral blood and pleural fluid in a patient with rheumatoid arthritis]. PMID- 1453835 TI - Laser stapedotomy: a comparative study of prostheses and seals. AB - During the past 13 years, a number of prostheses of differing design and tissue seals have been used in laser stapedotomy for otosclerosis. This study compares the results of three different configurations of prostheses and tissue seals in a series of 53 patients. In 19, a platinum wire Teflon piston was placed in the laser stapedotomy fenestra and crimped on the long process of the incus; autologous venous blood was infiltrated into the oval window niche as a sealing mechanism. In 8 patients, a stainless steel bucket-handle-type prosthesis was used with a blood tissue seal. In 26 patients, a segment of autogenous vein was clad onto the bucket-handle-type prosthesis and placed into the laser fenestra. Two tissue seals (blood and vein) were also compared. The results were compared with regard to several audiometric parameters. It would appear that the bucket handle/vein configuration improves air-bone gap closure in the low- and mid frequency speech range and also shows an advantage for air-bone gap closure to 10 dB or less compared to the other configurations in this study. Mean postoperative gaps were significantly less for vein compared to the blood tissue seal. Physiologic and surgical implications are discussed, and the vein-clad technique is illustrated. PMID- 1453836 TI - Same-day-stay head and neck surgery. AB - The purpose of this study was to determine if selective head and neck surgical procedures on a same-day basis are justifiable. Two hundred consecutive head and neck same-day procedures were reviewed, including 84 parotidectomies and 116 other procedures previously managed as inpatients. Of the 200 patients, 36 (18%) were admitted, 33 for overnight observation, and 164 (82%) were discharged the same day. There were no complications reported in the discharged patients and a later questionnaire showed that 97% of the patients were satisfied. The advantages of selective same-day procedures outweigh the disadvantages for otolaryngologist and patient. The study shows that same-day-stay head and neck surgery for selective procedures is safe, reasonable, and cost-effective, but the combined efforts of the otolaryngologists, nurses, and administrators are required. Because of rising healthcare costs, experts are predicting a significant increase in the next few years of outpatient surgery, including surgery of the head and neck. PMID- 1453837 TI - Classification of laryngotracheal stenosis. AB - Seventy-two cases of laryngotracheal stenosis treated from 1981 through 1991 were reviewed to develop a system of classification which would be useful in predicting the outcome of treatment. Decannulation and absence of dyspnea after exertion were the criteria of successful management. The probability of decannulation over time was computed using the Kaplan-Meier technique. Cox multiple regression analysis was used to determine the effects of independent variables (age, sex, etiology, site of stenosis, length of stenosis, diameter of stenosis, and surgical technique) on treatment success. The only factors with a significant effect on the outcome were site of stenosis and diameter of stenosis. A classification into four clinical stages of stenosis based on site of lesion was shown to effectively predict the likelihood of successful decannulation. PMID- 1453838 TI - The management of subglottic stenosis in patients with Wegener's granulomatosis. AB - Wegener's granulomatosis (WG) is a multisystem inflammatory disease characterized by vasculitis, granuloma formation, and necrosis. Among 158 patients treated at the National Institutes of Health during the past 24 years, 145 (92%) had an otolaryngologic manifestation of their disease and 25 (16%) had subglottic stenosis (SGS). SGS varied from asymptomatic to life-threatening. Sixteen (80%) of 20 patients with fixed SGS required surgical intervention, including manual dilations, carbon-dioxide laser resections, and laryngotracheoplasty (LTP). LTP was performed with and without microvascular reconstruction. Thirteen of the patients required tracheostomy and all 13 were ultimately decannulated. Five patients who repeatedly failed dilations and/or endoscopic laser surgery underwent LTP. Since 1987, two patients have undergone LTP with microvascular free flaps. Both patients were subsequently decannulated. The authors' experience demonstrates that management of SGS in WG is complex, requiring individualized frequent multimodality interventions to achieve satisfactory results. Microvascular laryngotracheal reconstruction should be considered in the surgical armamentarium for patients with persistent stenoses. PMID- 1453839 TI - Thermal effects on horseradish peroxidase uptake in laser nerve transections. AB - The authors previously reported that rat tibial nerves transected with CO2 or KTP/532 laser transmit less horseradish peroxidase (HRP) than those transected with a scalpel. This may be due to laser-specific effects or to thermal phenomena that are laser-independent. This study investigated potential thermal effects on the transmission of HRP through the tibial branch of the sciatic nerve in rats. Bilateral nerve transections were performed on 18 animals using a scalpel (control) or an electrocautery device, which simulated the thermal effects produced by lasers. HRP retrograde transport and deposition in the rat spinal cord were analyzed. Thirteen of 15 animals showed a higher number of HRP-labelled neurons on the scalpel side compared to the electrocautery side; a paired student's t test showed a significant difference (P = .028) in the numbers of HRP stained cell bodies between the control group (x = 687.13 +/- 119.3) and the electrocautery group (x = 388.1 +/- 111.2). In conclusion, reduced HRP uptake in tibial nerves transected with lasers may be in part due to thermal effects produced by the lasers. PMID- 1453840 TI - Cholesteatoma in the pediatric population: prognostic indicators for surgical decision making. AB - A review of surgical therapy for pediatric cholesteatoma at the Arkansas Children's Hospital was performed. Fifty-three children treated surgically for cholesteatoma were studied over a 10-year period. Primary acquired, or attic retraction cholesteatomas, were generally treated with a canal up tympanomastoidectomy; there were very few complications or secondary procedures in this group. Middle ear or secondary acquired cholesteatomas were initially treated by both canal up and canal down procedures; however, a large percentage of these patients eventually required an open cavity procedure. The presence of cholesteatoma in the sinus tympani strongly predicted failure to control disease with a canal up procedure (P < .05); conversely, the absence of matrix in the sinus tympani was predictive for success when a canal up procedure was used for attic cholesteatoma (P < .05). Finally, it was determined that follow-up was not adequate in our patient population. With this in mind, guidelines for the management of pediatric cholesteatoma will be presented. PMID- 1453841 TI - Surgical management of the thyroid nodule: patient selection based on the results of fine-needle aspiration cytology. AB - To determine whether the routine use of fine-needle aspiration (FNA) cytology reduces the rate of unnecessary surgery, the surgical pathology of 54 thyroidectomy patients who had preoperative FNA was compared to the results obtained with 24 thyroidectomy patients who did not have preoperative FNA. Twenty nine (85.3%) of the 34 patients who had a positive FNA were confirmed by histology to have a thyroid neoplasm; in 24 patients, the neoplasm was malignant. Two of the 17 patients who had a negative FNA but underwent thyroidectomy based on other factors were found to have thyroid cancer. Only 8 (33.3%) of the 24 surgical specimens of patients who did not have an FNA were found to be malignant. FNA had a sensitivity of 93.5% and a specificity of 75.0%. The results indicate that the routine use of FNA for patients with thyroid nodules reduces the incidence of unnecessary surgery. Furthermore, FNA alone is sufficient to identify most patients at risk and is, therefore, cost-effective. However, the presence of other findings suspicious of malignancy should preclude clinical decision making based on FNA alone. PMID- 1453842 TI - Hearing preservation following surgical removal of meningiomas affecting the temporal bone. AB - It is a common clinical impression that preservation of hearing is more often achieved when removing a meningioma than a similarly sized acoustic tumor. However, relatively few reports have focused on postoperative hearing results after meningioma removal, and detailed audiometric data are not commonly provided, particularly in the neurosurgical literature. During the past 16 years, 56 meningiomas affecting the temporal bone have been surgically removed at the House Ear Clinic. Hearing preservation was attempted in 16 (29%) of the 56 cases, and these were the focus of this study. The primary presenting symptom was otologic in 67% of these cases, including hearing loss as the primary symptom in 27%. Measurable postoperative hearing was present in 11 (92%) of 12 patients with postoperative audiograms available, and 8 (67%) of 12 patients had good hearing postoperatively. Hearing was preserved near the preoperative level (within 10 dB speech reception threshold and 15% speech discrimination) in 75% of cases. PMID- 1453843 TI - Petrous apex cholesteatoma: diagnostic and treatment dilemmas. AB - The diagnosis and treatment of petrous apex cholesteatoma is a difficult surgical challenge. This study is a review of 14 cases of cholesteatoma involving the petrous apex. These cholesteatomas originated as a congenital primary lesion or secondary to an acquired lesion. The cases were evaluated according to the clinical features, the intraoperative findings, the radiological findings, and the surgical approaches. In this series, 83% of the patients presented with hearing loss and 50% presented with facial nerve weakness or paralysis (House grade II to VI). Intraoperative and radiological features revealed frequent direct labyrinthine and supralabyrinthine cell spread. The transpetrous surgical approach was used in all cases. The main factors affecting the surgical approach to be adopted are the inaccessible nature of the petrous apex, the extent of disease, the degree of facial nerve function, and the need for the prevention of cerebrospinal fluid leaks and the recurrence of the lesion. PMID- 1453844 TI - Advanced carcinoma of the tongue: total glossectomy without total laryngectomy. Review of 80 cases. AB - Opinions are divided over the validity of total glossectomy without associated total laryngectomy for advanced carcinoma of the tongue. This retrospective study evaluates the oncologic and functional results obtained in 80 patients who underwent total glossectomy as a primary procedure or as salvage surgery. Satisfactory swallowing ability was obtained in 41 patients, and speech was understandable in 49 patients. The survival rate at 1 year was 65%, with early recurrence of the disease, which was especially frequent in patients with prior radiotherapy, being the major cause of death. The study confirms the poor prognosis of cases with mandibular involvement, and the fact that partial laryngectomy, when required, impairs functional results. In the light of the authors' experience, total glossectomy without total laryngectomy should only be undertaken in motivated and well-supported patients able to accomplish the difficult rehabilitation process. PMID- 1453845 TI - Amyloid of the facial nerve. AB - Although facial nerve paralysis has been reported in association with amyloidosis, histologic confirmation of facial nerve involvement with amyloid has not been previously demonstrated. A case of localized primary amyloidosis of the facial nerve is presented, and a new magnetic resonance technique for imaging the facial nerve is described. PMID- 1453846 TI - Diverticular imbrication and myotomy for Zenker's. PMID- 1453847 TI - Endoscopic adenoidectomy for relief of serous otitis media. PMID- 1453848 TI - Orbitocerebral complications of pseudomonas sinusitis. PMID- 1453849 TI - Microscopic and endoscopic ligature of the sphenopalatine artery. PMID- 1453850 TI - Documentation is a snap. PMID- 1453851 TI - The flexible (conservative surgical) approach for chronic otitis media in young children. PMID- 1453852 TI - Directory of otolaryngological societies. PMID- 1453853 TI - Drill-generated SNHL. PMID- 1453854 TI - Results of endoscopic sinus surgery. PMID- 1453855 TI - Squamous cell carcinoma of the tongue. PMID- 1453856 TI - Prognostic factors, outcomes and staging in ethmoid sinus surgery. AB - Although the literature is replete with papers discussing the results of surgery for chronic inflammatory sinus disease, critical comparison of results is difficult due to limited knowledge of the prognostic factors and the variable criteria reported for success. Detailed prospective and retrospective data collection was therefore undertaken to evaluate the results of surgical intervention in 120 patients who underwent endoscopic sinus surgery. Results were evaluated both by symptom questionnaire and by endoscopic follow-up examination. Over 240 data fields were collected on each patient, including information regarding presenting symptoms, endoscopic and computed tomography (CT) findings and surgical procedures performed. In order to reduce potential bias, the results of the follow-up questionnaires were compared to questionnaires from other patients unable to return for follow-up endoscopy. Mean follow-up time was 18 months. Potential prognostic variables were evaluated statistically. A strong correlation was identified between the extent of disease and the surgical outcome. Other identified potential factors appeared to have little or no significance. Therefore, a staging system for inflammatory sinus disease based on the extent of disease is suggested. PMID- 1453857 TI - Initial results of endothelial cell seeding following argon laser carotid endarterectomy. AB - This study evaluates the initial results of endothelial cell (EC) seeding following argon laser carotid endarterectomy. Venous endothelial cells were harvested from 12 dogs and cultured. A laser endarterectomy was performed on both carotids of each dog. One side was seeded with endothelial cells. Six dogs had both carotids harvested 1 hour after restoring blood flow. The others were harvested in 24 hours. The percentage of lumen covered with EC was evaluated by scanning electron microscopy. At 1 hour, the seeded arteries demonstrated 35 +/- 3 percent EC coverage, whereas the unseeded arteries had no EC coverage (P = 0.0002). At 24 hours, the seeded arteries had 58 +/- 15 percent EC coverage, whereas the unseeded arteries had no coverage (P = 0.01). Significant gross thrombus developed only in unseeded arteries (P = 0.047), two of which were occluded at 24 hours. EC seeding is beneficial following argon laser carotid endarterectomy resulting in improved patency and less surface thrombogenicity. PMID- 1453858 TI - Effect of force on ablation depth for a XeCl excimer laser beam delivered by an optical fiber in contact with arterial tissue under saline. AB - The effect of force applied to a 430 micron single fiber, delivering 60 pulses of 308 nm XeCl laser radiation at 20 Hz, on the ablation depth in porcine aortic tissue under saline has been investigated. Energy densities of 8, 15, 25, 28, 31, 37, and 45 mJ/mm2 were used. Force was applied by adding weights from 0 to 10 grams to the fiber. The fiber penetration was monitored by means of a position transducer. At 0 grams, the ablation depth increased linearly with incident energy density, but the fiber did not penetrate the tissue; with any weight added, the fiber penetrated the tissue at energy densities above 15 mJ/mm2. The fiber did not penetrate during the first several pulses, possibly due to gas trapped under the fiber. After these first pulses, a smooth linear advancement of the fiber began, which lasted until the pulse train stopped. The ablation depth increased with increasing energy densities and weights. This effect was largest above 25 mJ/mm2 where the ablation efficiencies (unit mm3/J), with weights added to the fiber, were substantially larger than values found in 308 nm ablation experiments described in the literature, which were conducted with either a focused laser beam or a fiber without additional force. The results imply that in 308 nm excimer laser angioplasty, force must be applied to the beam delivery catheter for efficient recanalization, and that experiments performed with a focused beam or without actual penetration of the fiber do not represent the situation encountered in excimer laser angioplasty. PMID- 1453859 TI - XeCl laser ablation of atherosclerotic aorta: optical properties and energy pathways. AB - The energetics of 308-nm excimer laser irradiation of human aorta were studied. The heat generation that occurred during laser irradiation of atherosclerotic aorta equaled the absorbed laser energy minus the fraction of energy for escaping fluorescence (0.8-1.6%) and photochemical decomposition (2%). The absorbed laser energy is equal to the total delivered light energy minus the energy lost as specular reflectance (2.4%, air/tissue) and diffuse reflectance (11.5-15.5%). Overall, about 79-83.5% of the delivered light energy was converted to heat. We conclude that the mechanism of XeCl laser ablation of soft tissue involves thermal overheating of the irradiated volume with subsequent explosive vaporization. The optical properties of normal wall of human aorta and fibrous plaque, both native and denatured were determined. The light scattering was significant and sufficient to cause a subsurface fluence (J/cm2) in native aorta that equaled 1.8 times the broad-beam radiant exposure, phi o (2.7 phi o for denatured aorta). An optical fiber must have a diameter of at least 800 microns to achieve a maximum light penetration (approximately 200 microns for phi o/e) in the aorta along the central axis of the beam. PMID- 1453860 TI - Cornea epithelial damage thresholds in rabbits exposed to Tm:YAG laser radiation at 2.02 microns. AB - We have determined exposure conditions for minimal damage to the corneal epithelium in rabbit using a continuous wave Tm: YAG laser operating in the TEM00 mode at incident powers between 80 and 450 mW. The 1/e beam diameter was 0.94 mm and exposure durations for threshold damage ranged from 4.3 to 0.08 sec. Calculated temperature increases on the beam axis 10 microns beneath the surface at the measured thresholds were essentially constant and averaged 44 degrees C. This is basically the same temperature increase found for threshold CO2 laser damage and suggests that the critical temperature damage model, which correlates CO2 laser damage, can predict damage thresholds for mid-infrared laser radiation. We also showed that reliable thresholds can be determined in freshly enucleated eyes, thus opening up the possibility of using available laser sources in laboratories not equipped and approved for animal experiments to determine damage thresholds. PMID- 1453861 TI - Immediate retinal adhesion by CO2 laser irradiation using a fiberoptic intraocular probe. AB - Using an experimental fiberoptically guided CO2 laser system, we produced lesions on fresh bovine retinas. These lesions were shown to achieve immediate measurable chorioretinal adhesion. This model provides preliminary data on the use of a fiberoptic CO2 laser probe to produce chorioretinal lesions and possible future use in intraocular surgery for retinal detachment. The advantages of using CO2 laser energy are minimal damage surrounding desired lesion and its versatility as a coagulator and cutter. With modifications, CO2 endolaser may have a role in intraocular surgery. PMID- 1453862 TI - Laser-induced experimental vascular occlusion using liposome-encapsulated ADP. AB - The therapeutic occlusion of retinal vessels is often helpful in treating various pathological conditions. We compared the combined effects of argon laser photocoagulation and adenosine diphosphate (ADP) released from temperature sensitive liposomes with argon laser photocoagulation alone on occlusion of retinal vessels in pigmented rats. In Group A, 8 eyes were treated with liposome encapsulated ADP and laser photocoagulation. In Group B, 8 eyes were treated with laser photocoagulation alone. The laser parameters (power, spot size, exposure time) were maintained at the same levels for both groups. The laser was focused on the retinal vessels at the optic nerve head. The treated retinal vessels were observed at time zero, day 1, day 4, and weekly for a period of 3 months. At time zero, 6 of 8 eyes were totally occluded in Group A, with best results obtained at 80 mW. Only 1 of 8 eyes in Group B achieved total occlusion. After 3 months, 4 of 8 eyes in Group A remained totally occluded; no eyes in Group B were occluded. Complete and permanent occlusion of retinal vessels can be achieved by using ADP and laser photocoagulation of lower power density than traditional laser photocoagulation alone. PMID- 1453863 TI - Effects of rapid pulsed CO2 laser beam on cortical bone in vivo. AB - Twenty rabbit femurs were used to study the effect of CO2 laser on cortical bone. Sixteen femurs were treated with 20 watts, 3 mm defocused beam, 2 KHZ spike pulse mode CO2 laser for 10 seconds through a circular window in the metaphysis. In four control femurs, the inner cortex was exposed without laser treatment. The animals were killed at 4 and 6 weeks and the specimens studied histologically. All laser-treated specimens showed thermal changes. Three histological zones were observed. A superficial zone of inner cortex close to the beam consisted mainly of carbonization or carbon ash during resorption. An intermediate zone consisted of bone necrosis and healing with associated areas of new bone formation. The deep zone of outer cortex had normal bone with no cellular damage. No such changes were observed in the control specimens. The CO2 laser can be used to generate a controlled zone of tissue ablation, which may make it a potentially useful tool for tumor margin cauterization. PMID- 1453864 TI - Percutaneous laser discectomy with the Ho:YAG laser. AB - A prototype Ho:YAG (2.15 microns) laser operating at 2-J/pulse, 3 Hz through a 600-microns fiber was employed to perform laser discectomies at the L3-4 disc through an 18G needle in five juvenile pigs. No temperature elevations were recorded in the posterior longitudinal ligament at the disc level and all animals recovered fully with no adverse sequelae, even immediately upon awakening from anesthesia. Pathologic examination demonstrated a wide swath of coagulation necrosis confined to the disc space. The Ho:YAG laser, owing to its close approximation to the intense 2.0 microns absorption band of water, appears to be a viable candidate for clinical trials of laser discectomy. PMID- 1453865 TI - Er:YAG laser ablation of enamel and dentin of human teeth: determination of ablation rates at various fluences and pulse repetition rates. AB - A pulsed Er:YAG laser (2.94 microns) was used to determine ablation depths per pulse of laser energy at 2 Hz and 5 Hz in human teeth cross sections of enamel and dentin. Ablation depths per pulse at 2 Hz in enamel of intact human teeth were measured and compared to ablation depths per pulse determined in enamel cross sections at 2 Hz. Close correlation was observed for ablation depths per pulse of laser energy between teeth cross sections and intact teeth for enamel. Photographs of lased holes at 2 Hz and 5 Hz indicated minimal thermal effects in enamel at fluences below 80 J/cm2. Minimal thermal effects in dentin were noted below 74 J/cm2. Scanning Electron Microscopy (SEM) pictures of lased dentin showed an irregular serrated surface. Results of this study suggest that the Er:YAG laser can effectively ablate enamel and dentin with minimal thermal effects at 2 Hz and 5 Hz. PMID- 1453866 TI - Centering balloon to improve esophageal photodynamic therapy. AB - A cylindrical balloon was developed to improve delivery of circumferential light for photodynamic therapy (PDT) of esophageal carcinoma. The balloon consisted of a 36-mm-long clear cylindrical membrane and a central tube to hold a cylindrical diffuser in the center of the lumen. Three isotropic probes were placed on the outside of the balloon to allow measurement of delivered light dose to the esophageal mucosa. The balloon was tested in the normal esophagus of 8 dogs that were injected with 4.0 mg/kg of PHOTOFRINR. Endoscopy was performed 48 hours following the injection, and under endoscopic observation the balloon assembly was passed, fixed in place, and inflated. A 1-cm cylindrical diffuser was passed into the central tube and 150, 300, and 600 Joules/cm of 630 nm laser light was delivered at 25 cm, 15 cm, and 5 cm proximal to the gastroesophageal junction. One control dog was illuminated using the cylindrical diffuser alone at doses of 300 and 600 Joules/cm of diffuser. Complete circumferential tissue response was obtained when the balloon was used. Relatively uniform light intensities were measured around the lumen. In contrast, noncircumferential and unpredictable PDT responses were generated when the cylindrical diffuser was used without the balloon. PMID- 1453867 TI - CO2 laser urethroplasty in the rabbit: a preclinical model. AB - Our previous work has shown that the CO2 laser can be successfully used in urethral reconstruction in a rat model. This new experiment investigates the use of the CO2 laser to perform a patch graft urethroplasty in the rabbit, as a preclinical model to its use in the repair of hypospadias in humans. Using sterile technique, a patch graft of preputial skin was welded in the repair of a standardized urethral defect in 10 rabbits. In another cohort, the same urethral defect was repaired using standard microsuture technique. In a control group the patch graft was placed with microsuture in a nonwatertight fashion. All animals were followed for 3 weeks. Histologic and radiologic analyses were done in a blinded fashion. Our study showed that CO2 laser repair, when compared to microsuture in urethral reconstruction, required 40% less operative time and produced better graft healing and less intraluminal scarring. PMID- 1453868 TI - Interstitial Nd:YAG laser ablation in normal rabbit liver: trial to maximize the size of laser-induced lesions. AB - In order to apply interstitial laser ablation to relatively small liver tumors in humans, it will be necessary to optimize the irradiation schedule. Nd:YAG laser was applied to normal rabbit liver in vivo at various power and energy outputs, including a protocol in which irradiation was repeated twice, with and without fiber tip advancement during the intermission. Ex vivo and in vivo tissue were also irradiated to determine the effect of perfusion on the lesion size. We obtained the same monotonic relationship between laser settings and lesion size in rabbit liver as we previously reported in rat liver. MR-guided fiber advancement between heating periods increased the transverse diameter of the lesion, and MR monitoring demonstrated this process. Our results suggest that repeated irradiation with brief intermissions, when combined with fiber advancement, may increase the lesion size. PMID- 1453869 TI - Interstitial laser photocoagulation: Nd:YAG 1064 nm optical fiber source compared to point heat source. AB - Interstitial laser photocoagulation (ILP) was performed in vitro in lean bovine and chicken muscle by delivering 1.6 W of continuous-wave Nd:YAG laser energy (1064 nm) from a 400-microns core optical fiber for 300s. The resulting thermal coagulation lesion was consistently larger when the delivered energy was deposited into a small steel sphere than when it was delivered freely into the tissue. Mathematical modelling confirms this result. This preliminary study suggests that a point heat source produces a larger volume of thermal coagulation than a point optical source (1064 nm) delivering the same power. PMID- 1453870 TI - Locomotory characteristics of fibroblasts within a three-dimensional collagen lattice: modulation by a helium/neon soft laser. AB - It has been postulated that low energy (soft) lasers can enhance wound healing. Considering the importance of cell locomotion in the wound healing process, we have studied the effects of a helium/neon laser upon the locomotory behaviour of a population of fibroblasts migrating within a three-dimensional hydrated collagen lattice. Statistical methods were used to quantify cell three dimensional trajectories obtained using a computer-assisted tracking system. A two-minute exposure of embryonic fibroblasts to soft laser light decreased the speed and increased the frequency and duration of stops compared to controls. The locomotory phenotype induced in embryonic fibroblasts by the laser light resembled that of the developmentally older c20 fibroblasts, which are known to express a more mature locomotory phenotype. The relevance of these results to wound healing is discussed. PMID- 1453871 TI - Laser reflections from surgical instruments. AB - The potential hazards to the eye and skin from accidental exposures caused by reflected laser beams from surgical instruments has long been of concern to operating room staff members. Reflectance values for argon neodymium:YAG and CO2 laser wave-lengths were measured from 29 reference surfaces used on surgical instruments. From these measurements, nominal hazard zones could be determined for typical reflection hazards. PMID- 1453872 TI - Local anesthetic-induced toxicity may be modified by low doses of flumazenil. AB - The purpose of this study was to investigate the influence of flumazenil on local anesthetic-induced acute toxicity. For each of the three tested anesthetics (etidocaine, mepivacaine and lidocaine) 6 groups of mice were treated by a single dose of flumazenil (0.125, 0.25, 0.5, 1 and 2 mg/kg), or an equal volume of saline, 15 minutes before the injection of the anesthetic (etidocaine: 50 mg/kg, mepivacaine: 110 mg/kg and lidocaine: 115 mg/kg). The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was not significantly modified by flumazenil. The convulsant activity of lidocaine and mepivacaine was significantly increased by flumazenil but not for etidocaine. Also, increasing doses of flumazenil decreased the time of latency to obtain lidocaine-induced convulsions. This effect was not obtained with etidocaine or mepivacaine. PMID- 1453873 TI - The effect of lowered extracellular Na+ concentration on ultraviolet light induced relaxation of vasoconstricted rabbit isolated thoracic aorta. AB - The effect of lowering extracellular ion concentration on ultraviolet (UV) light induced photorelaxation of norepinephrine(NE)-constricted rabbit isolated thoracic aorta was investigated. The magnitude of the photorelaxation response (similar to acetylcholine-induced, but not nitroprusside-induced, relaxation) progressively declined, in the absence of an effect on NE-induced vasoconstriction, as the total extracellular ion concentration was progressively reduced. This diminution in the photorelaxation response was duplicated by isosmotic lowering of the extracellular concentration of Na+, but not other ions, from 145 to 25 mM and was not restored by the replenishment of the Na+ deficiency by equimolar amounts of mannitol or Li+. In contrast, choline fully substituted for Na+. These findings suggest a fundamental difference in the ion dependency (and, hence, the mechanisms) of UV-induced photorelaxation and the vasorelaxations induced by acetylcholine or sodium nitroprusside. PMID- 1453874 TI - The effect of FK664, a new cardiovascular drug, on systemic capacitance vessels in anesthetized dogs. AB - To characterize the cardiovascular effect of FK664, a compound developed for the treatment of heart failure, the mean circulatory pressure (MCP), cardiac output and other parameters were measured in open-chest anesthetized dogs. Milrinone, a cardiotonic agent, and nifedipine, a calcium channel blocker were used as reference substances. Nifedipine (10 micrograms/kg), FK664 (0.1 mg/kg) or milrinone (0.1 mg/kg) given intravenously reduced the total peripheral resistance in a similar extent (35-40%). Whereas nifedipine had no effect on MCP, FK664 produced a significant decrease in MCP. Milrinone caused a minimal decrease in MCP, but not significantly. These results indicate that FK664 dilates the systemic capacitance vessels. This action to reduce the pre-load would be beneficial in the treatment of heart failure. PMID- 1453875 TI - Amylin. AB - Amylin is a 37 amino-acid peptide which is secreted from the pancreatic islets of Langerhans. It has major sequence homology with calcitonin gene related peptide. Amylin can precipitate out in these cells to form amyloid. Amylin is secreted by similar stimuli to those that secrete insulin. Amylin has a number of effects that may counteract the effect of secreted insulin, i.e., decreased second phase insulin secretion, increased hepatic glucose output, and inhibition of insulin effects on skeletal muscle. It must, however, be recognized that in many cases the doses necessary to produce these effects appear to be supraphysiological. The putative role of amylin in the hyperglycemia of aging and Type II diabetes mellitus therefore remains controversial. Amylin has a number of other effects including inhibition of osteoclastic activity, vasodilatation, anorectic effects and enhanced memory retention. This review postulates a role for amylin in the pathogenesis of a number of age-related changes. PMID- 1453876 TI - Long-term effects of aluminium on the fetal mouse brain. AB - Potentially noxious substances may act as fetal teratogens at levels far lower than those required to produce detectable effects in adults, and behavioural teratogenicity may occur at levels lower than those which produce morphological teratogenesis. Aluminium (Al) is a potential neurotoxin in adults. Since pregnant women may be exposed to untoward levels of Al compounds under certain conditions, we have examined the long-term effects of treating the pregnant mouse with intraperitoneal or oral aluminium sulphate on brain biochemistry and behaviour of the offspring. The cholinergic system, as evaluated by the activity of choline acetyltransferase (ChAT), was affected differentially in different regions of the brain, and still showed significant effects in the adult. Differences between the intraperitoneal and oral series in the magnitude of effect seen in the regions of the brain probably reflect differences in the effective level of exposure. Growth rate and psychomotor maturation in the pre-weaning mouse were affected in the intraperitoneal series only, showing a marked post-natal maternal effect. PMID- 1453877 TI - Combination therapy with an antioxidant and a corticosteroid prevents autoimmune diabetes in NOD mice. AB - Oxygen free radicals have been implicated as mediators of pancreatic islet beta cell damage in autoimmune, insulin-dependent diabetes mellitus (IDDM). In this study, we show that the antioxidant, probucol, produced only a small decrease in diabetes incidence in nonobese diabetic (NOD) mice, an animal model for human IDDM. However, combination of probucol with the antiinflammatory corticosteroid, deflazacort, produced an early synergistic effect, delaying diabetes onset by 3 weeks, and a later additive effect, decreasing diabetes incidence from 68% (17 of 25 mice) to 23% (6 of 26 mice, p < 0.005). Protection against diabetes by the combination of probucol and deflazacort was associated with a significant decrease in pancreatic islet infiltration by macrophages/lymphocytes (insulitis) and prevention of islet beta cell loss. PMID- 1453878 TI - Increase of plasma IL-6 concentration with age in healthy subjects. AB - The present study demonstrated that plasma IL-6 concentration was higher in older subjects than in younger ones and significantly in the male group (P = 0.02); Spearman rank correlation showed that plasma IL-6 concentration was positively correlated with age (r = 0.28, N = 55, P < 0.05); there was a highly significant correlation between the concentrations in plasma IL-6 and IL-1 alpha (r = 0.51, N = 52, P < 0.001). These findings suggest the possibility that age-related changes of plasma IL-6 and IL-1 alpha may provide a pathological basis for the susceptibility to such illness as commonly occurs in elderly people, especially Alzheimer's disease as the two interleukins can induce the production of alpha 1 antichymotrypsin and beta-amyloid protein precursor. PMID- 1453879 TI - PMA-sensitive protein kinase C is not necessary in TRH-stimulated prolactin release from female rat primary pituitary cells. AB - In GH3 cells and other clonal rat pituitary tumor cells, TRH has been shown to mediate its effects on prolactin release via a rise of cytosolic Ca2+ and activation of protein kinase C. In this study, we examined the role of protein kinase C in TRH-stimulated prolactin release from female rat primary pituitary cell culture. Both TRH and PMA stimulated prolactin release in a dose-dependent manner. When present together at maximal concentrations, TRH and PMA produced an effect which was slightly less than additive. Pretreatment of rat pituitary cells with 10(-6) M PMA for 24 hrs completely down-regulated protein kinase C, since such PMA-pretreated cells did not release prolactin in response to a second dose of PMA. Interestingly, protein kinase C down-regulation had no effect on TRH induced prolactin release from rat pituitary cells. In contrast, PMA-pretreated GH3 cells did not respond to a subsequent stimulation by either PMA or TRH. Pretreatment of rat pituitary cells with TRH (10(-7) M, 24 hrs) inhibited the subsequent response to TRH, but not PMA. Forskolin, an adenylate cyclase activator, stimulated prolactin release by itself and in a synergistic manner when incubated together with TRH or PMA. The synergistic effects of forskolin on prolactin release was greater in the presence of PMA than TRH. Down-regulation of protein kinase C by PMA pretreatment abolished the synergistic effect produced by PMA and forskolin but had no effect on those generated by TRH and forskolin. sn 1,2-Dioctanylglycerol (DOG) pretreatment attenuated the subsequent response to DOG and PMA but not TRH. The effect of TRH, but not PMA, on prolactin release required the presence of extracellular Ca2+. In conclusion, the mechanism by which TRH causes prolactin release from rat primary pituitary cells is different from that of GH3 cells; the former is a protein kinase C-independent process whereas the latter is at least partially dependent upon the activation of protein kinase C. PMID- 1453880 TI - 5c,11c,14c-eicosatrienoic acid and 5c,11c,14c,17c-eicosatetraenoic acid of Biota orientalis seed oil affect lipid metabolism in the rat. AB - The effects of 5c,11c,14c-eicosatrienoic acid (20:3BSO) and 5c,11c,14c,17c eicosatetraenoic acid (20:4BSO), polyunsaturated fatty acids (PUFA) contained in Biota orientalis seed oil (BSO), on lipid metabolism in rats were compared to the effects of fats rich in linoleic acid (LA) or alpha-linolenic acid (ALA) under similar conditions. The potential effect of ethyl 20:4BSO as an essential fatty acid also was examined in comparison with the ethyl esters of LA, ALA and gamma linolenic acid (GLA). BSO- and ALA-rich fat decreased the concentration of plasma total cholesterol, high density lipoprotein cholesterol, triglyceride and phospholipid as compared to LA-rich fat. BSO was more effective in reducing plasma cholesterol concentrations than was the ALA-rich fat. Dietary BSO markedly decreased the hepatic triglyceride concentration as compared to the LA-rich or ALA-rich fats. Aortic production of prostaglandin I2 tended to decrease in rats fed BSO or ALA-rich fat compared to those fed the LA-rich fat. Adenosine diphosphate-induced platelet aggregation was similar in the three groups. The proportion of arachidonic acid (AA) in liver phosphatidylcholine (PC) of rats fed BSO was lowest compared to that of rats fed ALA-rich or LA-rich fats. Administration of 20:4BSO, ALA or GLA to essential fatty acid-deficient rats decreased the ratio of 20:3n-9 to AA in liver PC to the same extent; administration of LA was more effective. The results indicate that the effects of specific PUFA contained in BSO on lipid metabolism are different from those of LA and ALA. It is also suggested that 20:4BSO may exhibit some essential fatty acid effects. PMID- 1453881 TI - Inhibitory effect of curcumin on fatty acid desaturation in Mortierella alpina 1S 4 and rat liver microsomes. AB - An extract of rhizomes of Curcuma longta L. (turmeric) inhibited the desaturation of dihomo-gamma-linolenic acid (DGLA) in the arachidonic acid (AA) producing fungus Mortierella alpina 1S-4. The factor responsible for this phenomenon was isolated and identified as curcumin (diferuloyl methane). Mycelial DGLA levels increased about two-fold (22.3 mg/g dry weight) with a concomitant decrease in AA levels when the fungus was cultivated with curcumin. The 50% inhibitory concentration against delta 5 desaturase was 27.2 microM. Curcumin also inhibited rat liver microsomal delta 5 and delta 6 desaturases. PMID- 1453882 TI - Nonesterified fatty acids in normal and diabetic rat sciatic nerve. AB - Alloxan-induced diabetes in rats results in elevated levels of nonesterified fatty acids (NEFA) in whole sciatic nerve and its endoneurium. Increases in NEFA levels are more pronounced in whole diabetic nerve (40% over control) than in its endoneurial portion (20-30%). Alterations in the composition of phospholipid fatty acids are observed as well, including an increase in linoleate (18:2n-6) in endoneurial phosphatidylethanolamine and a decrease in arachidonate (20:4n-6) in both phosphatidylethanolamine and phosphatidylinositol of diabetic nerve. PMID- 1453883 TI - Dietary fat and fatty acids modulate cholesterol cholelithiasis in the hamster. AB - We tested two hypotheses, i) whether the type and the amount of fat in the diet will affect the formation of cholesterol gallstones in the hamsters, and ii) whether palmitic acid, a major fatty acid component of butterfat, can act as a potentiator of cholesterol cholelithiasis in the hamster. Young, male golden Syrian hamsters (Sasco) were fed a semipurified diet containing casein, corn starch, cellulose and cholesterol (0.3%) to which various types and amounts of fat (butterfat, olive oil, menhaden oil, corn oil) were added. All diets contained 2% corn oil to supply essential fatty acids to the growing hamsters. No deaths or illness occurred during the experiment. Animals fed the semipurified diet plus 4% butterfat (group 1) had a gallstone incidence of 63%. Replacement of butterfat with either olive oil, corn oil or menhaden oil prevented the formation of cholesterol gallstones entirely (groups 2-4). When total butterfat was increased from 4% to 8% (group 8), the incidence of cholesterol gallstones increased to 80%. Substitution of 4% olive oil (group 5), corn oil (group 6), or menhaden oil (group 7) for the additional 4% butterfat significantly reduced gallstones to 35%, 45% and 30%, respectively. The replacement of 4% butterfat with 1.2% palmitic acid gave the highest incidence of cholesterol gallstones (95%). These results suggest that butterfat (and one of its components, palmitic acid) intensifies gallstone formation in this model whereas mono- and polyunsaturated fats act as inhibitors of cholesterol cholelithiasis. A fatty acid, possibly palmitic acid, appears to act as lithogen in our model. PMID- 1453884 TI - Changes in blood lipids and fibrinogen with a note on safety in a long term study on the effects of n-3 fatty acids in subjects receiving fish oil supplements and followed for seven years. AB - The present study was designed to assess the effectiveness of the n-3 fatty acids in modifying serum total, low density lipoprotein and high density lipoprotein (HDL) cholesterol, as well as serum triglycerides, over a seven-year period. Changes in plasma fibrinogen were recorded and long term safety assessed. A total of 365 subjects with ischemic heart disease (IHD), hyperlipidemia or a strong family history of IHD had their diet supplemented with MaxEPA (Seven Seas Ltd., Hull, England) fish oil containing 18-19% eicosapentaenoic acid. Venous blood samples were taken at regular intervals for lipid and fibrinogen assays and routine clinical chemistry and hematological profiling. Current medication was recorded and no further dietary modification was attempted. Triglyceride and fibrinogen were significantly reduced, whereas a significant reduction in total cholesterol occurred only in the subjects with a pre-oil level greater than 6.5 mmol/L. HDL cholesterol significantly increased over the study period. Clinical chemistry and hematological profiles were not adversely affected, and platelet count did not change significantly. The type of lipid changes observed were those usually considered antiatherogenic. Reducing fibrinogen may result in beneficial changes in the pathological processes leading to thrombotic occlusion. The consumption of MaxEPA by our patients over a seven-year period did not indicate any adverse effects. PMID- 1453885 TI - Ascorbate and phenolic antioxidant interactions in prevention of liposomal oxidation. AB - Efficient prevention of membrane lipid peroxidation by vitamin E (alpha tocopherol) may involve its regeneration by vitamin C (ascorbate). Conceivably, the efficacy of antioxidants designed as therapeutic agents could be enhanced if a similar regeneration were favorable; thus, a model membrane system was developed which allowed assessment of interaction of phenolic antioxidants with ascorbate and ascorbyl-6-palmitate. Ascorbate alone (50-200 microM) potentiated oxidation of soybean phosphatidylcholine liposomes by Fe2+/histidine-Fe3+, an effect which was temporally related to reduction of Fe3+ generated during oxidation. Addition of 200 microM ascorbate to alpha-tocopherol-containing liposomes (0.1 mol%) resulted in marked, synergistic protection. Accordingly, in the presence but not absence of ascorbate, alpha-tocopherol levels were maintained relatively constant during Fe2+/histidine-Fe3+ exposure. Probucol (4,4'-[(1-methylethylidine)bis(thio)]bis[2,6-bis(1,1- dimethylethyl)]phenol), an antioxidant which prevents oxidation of low density lipoproteins, and its analogues MDL 27,968 (4,4'-[(1-methylethylidene)bis(thio)]bis[2,6- dimethyl]phenol) and MDL 28,881 (2,6-bis(1,1-dimethylethyl)-4-[(3,7,11- trimethyldodecyl)thio]phenol) prevented oxidation but exhibited no synergy with ascorbate. Ascorbyl-6-palmitate itself was an effective antioxidant but did not interact synergistically with any of the phenolic antioxidants. Differential scanning calorimetry revealed significant differences among the antioxidants in their effect on the liquid-crystalline phase transition of dipalmitoyl phosphatidylcholine (DPPC) liposomes. Both alpha-tocopherol and MDL 27,968 significantly reduced the phase transition temperature and the enthalpy of the transition. MDL 28,881 had no effect while probucol was intermediate. The potential for ascorbate or its analogues to interact with phenolic antioxidants to provide a more effective antioxidant system appears to be dictated by structural features and by the location of the antioxidants in the membrane. PMID- 1453886 TI - 31P NMR of tissue phospholipids: competition for Mg2+, Ca2+, Na+ and K+ cations. AB - Phosphatidylcholine (PC), phosphatidylethanolamine (PE), ethanolamine plasmalogen (EPLAS), sphingomyelin (SPH), phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin (CL), phosphatidylglycerol (PG) and phosphatidic acid (PA) were dispersed together in Cs(ethylenedinitrilo)tetraacetic acid-scrubbed chloroform/methanol solution, and high resolution 31P nuclear magnetic resonance spectra were recorded. In separate titration experiments, Mg2+ and Ca2+ were added to the dispersed phospholipid mixture to determine the relative interaction potentials of each of the phospholipids for each of the added cations. The association of cations with individual phospholipids was indicated by 31P chemical-shift changes, signal broadening, signal quenching or a combination of these. The titrations revealed that CL had the highest, and PA the next highest, interaction potential for Mg2+ cations. In contrast, PS and PA had the highest, and CL the next highest, interaction potential for Ca2+. Considering only interactions with Ca2+ ions, the phospholipids can be divided into three distinct groups: PS and PA (high interaction potential); CL, PI and PG (intermediate interaction potential); and EPLAS, PE, SPH and PC (essentially no interaction potential). The two phospholipids with the least interaction potential for either of the alkaline-earth cations were PC and SPH. Na+ and K+ ion interactions with PA, CL, PI and PG were unique and resulted in positive chemical-shift changes relative to the chemical shifts in the presence of Cs+ ions. Relative to both Cs+ and K+ ions, chemical shifts in the presence of Na+ ions were deshielded delta greater than 0.1 ppm in the order PA greater than CL greater than PI greater than PG. PMID- 1453887 TI - The determination of tissue ethanolamine levels by reverse-phase high-performance liquid chromatography. AB - A rapid and sensitive procedure for the determination of ethanolamine levels in mammalian tissues is reported. Ethanolamine was extracted from the tissue with a chloroform/methanol mixture, followed by phase separation. The aqueous phase was subjected to charcoal chromatography and the eluant was derivatized with phenylisothiocyanate. The amount of phenylthiocarbamyl (PTC) ethanolamine in the tissue extract was determined by reverse-phase high-performance liquid chromatography. Quantitation of PTC ethanolamine was linear between 0.1-1.0 nmol. The pool sizes of ethanolamine in hamster heart, liver and kidney were found to be 1.07, 0.92 and 1.11 mumol/g wet weight, respectively. The sensitivity of the method would allow the determination of ethanolamine in very small tissue samples. PMID- 1453888 TI - Black teenage pregnancy: a sociomedical approach. AB - This article is based on a literature and descriptive empirical investigation into the incidence of, and other factors associated with black teenage pregnancy in Africa and South Africa. The research survey was conducted in Port Elizabeth, South Africa. A sample of 145 black teenagers, between the ages of 12 and 17 years, who gave birth during four months in 1990 was interviewed. Socioeconomic, biographical and medical data were obtained. All of which point to an urgent need for a multidisciplinary and holistic approach to age-related sex education for adolescents of both sexes and their parents; socio-economic problems facing the family; ways of preventing school drop out and further unplanned and unwanted pregnancies among teenagers. PMID- 1453889 TI - Tattooing and high-risk behaviour among drug addicts. AB - One hundred and seventy-five patients treated at the drug dependence outpatient ward of the Psychiatric University Clinic of Vienna were investigated in February 1990 using a standardized questionnaire which included questions concerning tattoo behaviour. The tattooing procedure, often carried out in prison and employing unsterile equipment, is a possible way of HIV-1 transmission. It is recommended that the fragmentary legislation in Austria be rewritten and made more effective. According to a ministerial order only medical doctors are allowed to procure a licence for tattooing as it is an invasive procedure. Therefore no licensed tattooing establishments controlled by public health offices exist. Their legal existence would guarantee a hygienic standard and reduce the danger of infection. PMID- 1453890 TI - Appeals from disciplinary rulings of patients' complaints regarding physicians' conduct. AB - In 1984 and 1985 the Danish National Board of Health received a total of 1,062 complaints from patients regarding alleged physician negligence. The board has disciplinary powers over physicians in cases of negligence, and advises the Attorney General in cases of gross negligence which are referred to the court. The investigation found that 17% of the board's rulings were taken on appeal, of these 9% were either wholly or partly upheld. Physicians did not appeal frequently (2%), but their appeals were more often upheld (32%) than was the case in respect of patients' appeals (15% and 4.4% respectively). Evaluation of the cases taken on appeal did not provide support for extending the right to appeal. The consequences of such an extension are, however, discussed in the light of subsequent limitations imposed on the right to appeal and the more well established and comprehensive provisions for appealing that exist in some neighbouring countries. PMID- 1453891 TI - Medical and biological progress and the European Convention on Human Rights. AB - The advances made in life sciences are one of the most significant features of the 20th century scientific revolution and human rights obviously enjoy prominence among the legal issues affected by the development of medicine. The case law of the organs of the European Convention on Human Rights arising from developments in the biomedical sciences is reviewed. The approach of especially the European Commission on Human Rights to the consequences of advances in the life sciences on the protection of the individual's physical integrity and the protection of freedom of thought and private and family life is analysed. 'Contrary to what we are led to believe, it is not from the starting-point of biology that a particular idea of man can be formed; on the contrary, it is from the starting-point of a particular idea of man that biology can be used to serve him': F Gros, F Jacob & P Royer Life Sciences and Society (1979) 288. PMID- 1453892 TI - New Zealand's medical manslaughter. AB - Doctors in New Zealand may be prosecuted for manslaughter if patients die as a consequence of the doctor's failure to exercise reasonable knowledge, skill and care. The requirement to use reasonable knowledge, skill and care has been held to be breached in New Zealand if a doctor is merely careless. No distinction is made between 'criminal negligence' and the negligence standard applicable in civil law. This article examines New Zealand's law relating to medical manslaughter with particular reference to the case of R v Yogasakaran [1990] 1 NZLR 399 which was the subject of a petition to the Privy Council on 30 January 1991. PMID- 1453893 TI - The neglected intermediate premise in the forensic expert's testimony. AB - The testimony of most expert witnesses is reducible to a syllogism: The expert derives a relevant opinion (the conclusion) by applying a general theory or technique (the major premise) to the specific facts of the case (the minor premise). Legal commentators have tended to focus on the expert's major premise to the neglect of the minor premise. Thus, legal analysts have devoted little attention to the question of the forensic expert's use of proper test protocol. This neglect can result in the admission of erroneous scientific testimony. The neglect also represents a missed opportunity--the legal system's opportunity to give the forensic community additional incentive scrupulously to follow correct test procedures. PMID- 1453894 TI - Legal aspects of forensic psychiatry in South Africa. AB - The current political changes in South Africa have focused attention on matters such as the availability of medical and psychiatric services for all. These services have been stretched to breaking point due to waves of crimes of violence which seem to go in tandem with the process of democratization. These questions are discussed and some possible inadequacies of the forensic sciences in the criminal justice system are considered. PMID- 1453895 TI - Preventive outpatient civil commitment and the right to refuse treatment: can pragmatic realities and constitutional requirements be reconciled? AB - This article examines the concept of preventive outpatient civil commitment as a mechanism for controlling the behaviour of the chronically mentally ill. The goal of preventive outpatient civil commitment is to intervene at an early stage to prevent further deterioration of a mentally ill person's state. In the jurisdictions in the United States which have enacted preventive outpatient civil commitment statutes, there is a lesser standard required for outpatient commitment than for inpatient commitment. For outpatient commitment, there generally only needs to be a finding of mental illness and a conclusion that without treatment a person's mental illness will further deteriorate. This standard often clashes with the civil liberties of those being committed, particularly with the right to refuse treatment. This article explores preventive outpatient civil commitment in relation to the historic right to refuse treatment by examining the antithetical positions of the state's authority to treat and the mental health client's interest in liberty. The article concludes that both of these positions ignore the possibility that, through the development of an adequate community care service system, the reality of the mentally ill in the community may be reconciled with a civil liberties perspective. '[The] [c]onstitutional right to privacy...is an expression of the sanctity of individual free choice and self-determination as fundamental constituents of life. The value of life as so perceived is lessened not by a decision to refuse treatment, but by the failure to allow a competent human being the right of choice.' PMID- 1453896 TI - Infanticide: new medical considerations. AB - A relationship between disturbed hormonal and metabolic equilibrium during puerperium and ensuing mental and emotional imbalance has been postulated for a long time. In England and Wales this consideration has resulted in the crime of infanticide being reduced from murder to manslaughter. Recent data indicate that the therapeutic and even routine administration by physicians of powerful vasoactive agents during puerperium, and particularly that of ergot derivatives, is probably the most frequent factor leading to 'pure puerperal psychosis'. It is proposed, therefore, that this psychosis is in fact, in most instances, a form of ergotism and its signs and symptoms and consequences, including coincidental infanticide, themselves are actually manifestations of acute ergot poisoning. It is suggested that based on this information a thorough re-evaluation of the relevant legal concepts is necessary. PMID- 1453897 TI - International migration and medical credentialling. AB - The Single European Act of July 1987, coupled with various other regional and national laws, the purposes of which open borders to the free movement of peoples, goods and services, is soon to be put into operation. Although awaited with much eagerness and expectation, there is also a need for strategic planning in order adequately to address new and possibly ominous legal and medical practice problems. In the United States, a National Practitioner Data Bank, which went into full operation in September 1990 was created to monitor physicians, nurses and other health care providers involved in negligence actions which result in the payment of moneys by settlement or by verdict, and to prevent those whose licences have been suspended, revoked or restricted in any fashion in one state from practising in another based upon reciprocity licensure or board certification criteria. In order to protect patients from abuse by uncredentialled individuals or dangerous clinicians, and further to protect institutions from liability incurred by inadequate credentials checks or through ostensible liability, the creation of a practitioner data bank utilizing modern data gathering, storage and retrieval methods is proposed for the European Community. It should be created under the auspices of the United Nations- possibly through the World Health Organization which already accredits medical education and training programmes--and should be charged with creating uniform standards of professional practice; certifying professionals; and serving as a credentials' clearing house for the health care industry. PMID- 1453898 TI - New Israeli psychiatric legislation. AB - For about 35 years, the 1955 Mental Act served as the main legal tool applied in the treatment of admitted patients in Israel. The law was wearing out, although 'patched up' repeatedly, and could no longer express 'the spirit of the times'. After many vicissitudes, a new Mental Act was implemented in 1991. The various areas dealt with in the new law are described and discussed. Special attention is focused on two issues: patients' rights and the decisions pertaining to enforced examination, hospitalization and treatment. PMID- 1453899 TI - The insanity defense: a South African perspective. AB - The insanity defence has always been a contentious issue. This study was carried out on a sample of 95 consecutive forensic, psychiatric observation cases. The cost-effectiveness of ordering routine investigations during the observation period appeared to be questionable since the results of selective special investigations yielded more useful information. It was found that there was little calculated abuse of the insanity defence, but that the situation was rather one of barely literate persons naively attempting to use it, especially in cases of serious crime. The incidence of these naive users might have been greatly reduced had there been adequate screening before the accused were sent for observation. The court generally accepted the psychiatrist's opinion with regard to mental illness and criminal responsibility. It, however, differed on occasion when it came to the disposal of those accused who were found to be mentally ill. PMID- 1453900 TI - Some psychological reactions of rape victims. AB - This article delineates the psychological reactions of rape victims from a psychodynamic vantage point. Rape, an act of violence, results in psychic trauma. The authors attempt an understanding of the psychological sequelae of rape. PMID- 1453901 TI - Intramarital illegitimacy. AB - Discovering cases of children born to married women by men not their husbands is generally difficult. Legal involvements with regard to paternity, divorce and litigious paranoids also have applicability to cases of pregnancy by donor insemination. The child's right to information regarding paternity is the same in both types of cases, and is relevant with respect to matters of heredity as well as, in some cases, counselling and psychotherapy. PMID- 1453902 TI - Escherichia coli: rapid identification by chromogenic tests. AB - A system has been assessed for the identification of Esch. coli using a rapid triple chromogenic test which relies on the ability of the organism to produce a beta-galactosidase, a beta-glucuronidase, and indole. Coliforms which had been fully identified were tested by this system. Of 512 non-Esch. coli strains there were no false positives, whereas of 514 Esch. coli strains 486 (94.5%) were found to give positive results. Two hundred and twenty-one coliforms that had been isolated from blood cultures were also tested using the colistrip in advance of, or without knowledge of the API 20E result. The test was found to be 100% specific and 94% sensitive for the 105 Esch. coli strains. The test was rapid, simple to perform and economical. PMID- 1453903 TI - High level gentamicin resistance in enterococcal and streptococcal isolates from blood culture. AB - The combination of an aminoglycoside with a cell wall active agent is often necessary for the satisfactory management of serious enterococcal and streptococcal infections. High level gentamicin resistance (MIC > 1000 micrograms/ml) eradicates the synergy between these two classes of antibiotics and treatment of these infections becomes difficult. Over a four year period we assessed the susceptibility of blood culture isolates of enterococci, Streptococcus agalactiae (group B), and clinically significant viridans-type streptococci. The susceptibility of the organisms to gentamicin could be determined utilizing high content aminoglycoside discs. We report an increasing prevalence of high level gentamicin resistance in enterococci in South London, with 44% of isolates being resistant in the first quarter of 1991. None of the streptococcal isolates demonstrated high level gentamicin resistance. We recommend screening for high level gentamicin resistance in all enterococcal and streptococcal cases where aminoglycoside-penicillin synergy is desired. PMID- 1453904 TI - Speech recognition and the clinical microbiology laboratory. AB - Keyboard entry of large amounts of diagnostic data is a laborious task. Any transcription errors that occur may pass undetected by 'non-technical staff' employed to input these data. The object of this project was to design a system, based on a Marconi 'Macrospeak' Speech Recogniser, for 'on line' laboratory entry of data generated from the microbiological examination of specimens of urine. Six parameters considered important to the success of the system were assessed: accuracy, speech recognition, reproducibility, speed, user friendliness, and cost effectiveness. The system performed well under the test conditions examined. 'On line' hands free entry of diagnostic data, using speech recognition, may be a practical alternative to more conventional means of data entry. PMID- 1453905 TI - Urinary amphetamines, benzodiazepines and methadone: cost-effective detection procedures. AB - Cost-effective immunoassays for the detection of amphetamines, benzodiazepines, and methadone in urine have been developed using Syva EMIT reagents and a Cobas Bio centrifugal analyser. With this method up to 2470 samples can be assayed with a single 100 test EMIT kit while maintaining acceptable precision. Mean CVs of 3.8-6.6% were obtained for concentrations around the manufacturer's recommended threshold level (300 micrograms/l). Comparison of the methods with the Abbott TDx system showed good correlation for methadone. The methods compared less well for amphetamines, and it was not possible to obtain a useful correlation for benzodiazepines. Heat treatment prior to analysis did not affect the detection of benzodiazepines and methadone; there was a mean decrease of 14% for amphetamines. PMID- 1453906 TI - Carbamylation and glycosylation of haemoglobin in vitro: effects of cyanate and glucose. AB - An in vitro system that is independent of any haemodynamic influence and other physiological controls was designed to study the formation of carbamylated and glycosylated haemoglobin, by the use of cyanate and glucose respectively, incubated with whole-blood from normal healthy subjects. In this system the formation of glycosylated haemoglobin is more favourable than that of carbamylated haemoglobin. The effect of glucose in reducing the formation of carbamylated haemoglobin is greater than the effect of cyanate on the formation of glycoslyated haemoglobin. There is a strong correlation coefficient (r = 0.9, P < 0.005) for the relationship between the formation of carbamylated and glycosylated haemoglobin in this system. PMID- 1453907 TI - Immunohistochemical demonstration of B and T-lymphocyte cell surface markers: an assessment of tissue transport/storage media. AB - A number of solutions were tested on lymphoid tissue with a view to devising a tissue transport/long-term storage medium which would preserve the morphology and antigenicity of lymphocytes, for demonstration of B- and T-cell surface markers using monoclonal antibodies. Some of the solutions produced total loss of any recognisable tissue structure, but one newly-devised medium gave excellent preservation of morphology and nuclear detail, together with extremely good monoclonal antibody staining. This sterilised medium, Carmichael's medium*, contains a buffer and cryoprotectant: it forms a gel at 4 degrees C, but it is easily liquefied in warm water just prior to immersion of the biopsy. Sections from tissue preserved in Carmichael's Medium were found to be of equally good quality as, and in some cases better than, those which had been fresh frozen. *International patents are currently pending on the formulation of this medium, which will be available commercially through Raymond Lamb Ltd, London, England, UK. PMID- 1453908 TI - Anti-paternal lymphocyte antibodies: a modified cellular enzyme-linked immunospecific assay (CELISA). AB - A cellular enzyme-linked immunospecific assay is described which is ideally suited to measuring the IgG antibody response to donor-specific lymphocyte infusions. The procedure is simple, sensitive, specific and objective. PMID- 1453909 TI - Syphilis diagnosis: screening by enzyme immunoassay and variation in fluorescent treponemal antibody absorbed (FTA-ABS) confirmatory test performance. AB - Four fluorescent treponemal antibody absorbed (FTA-ABS) test kits were evaluated with 86 treponemal and 84 non-treponemal sera selected with enzyme immunoassay (EIA). Agreement between all four kits was 63% for treponemal, and 50% for non treponemal, sera. Discrepancies with treponemal sera were associated with low levels of antibody characterised by T. pallidum haemagglutination assay (TPHA) titres < or = 160 and a negative Venereal Diseases Research Laboratory (VDRL) test. Discrepancies with non-treponemal sera were significantly associated with false reactivity on screening with EIA. Possible reasons for the differences obtained between kits, the importance of screening policies for pre-selecting sera, and the significance of equivocal (borderline) reactions on positive and negative predictive values are discussed. PMID- 1453910 TI - Glutamate pyruvate transaminase as an indicator of infection with Plasmodium falciparum. AB - A correlation is shown between the presence of trophozoites and/or gametocytes of Plasmodium falciparum in thick and/or thin blood films, with the enzyme glutamate pyruvate transaminase (GPT) and a marked increase in serum GPT as a probable consequence of the presence of malaria parasite inferred. It is suggested that serum GPT levels may be used as a reliable marker for malaria infection, but only complementary to microscopic detection of falciparum malaria, rather than being specifically diagnostic. PMID- 1453911 TI - Anti-HBs detection: a modified passive haemagglutination assay. AB - Modification of a commercial haemagglutination assay for the detection of anti HBs has reduced the test time from over one hour to approximately 25 min. increased sensitivity ten-fold without any prozoning, maintained specificity and reduced costs by 90%. The modification consists of diluting the reagent cells ten fold; these are then added to dilutions of test serum in a V-well microplate. After incubation, plates are centrifuged and then inclined at 70 degrees. Positive and negative reactions can be clearly distinguished within approximately 10 minutes. PMID- 1453912 TI - Colorectal cancer. AB - Two current areas of interest regarding colorectal cancer are identification of its genetic and environmental causes, and evaluation of the possibilities of implementing screening programmes for asymptomatic disease in the general population. These issues are addressed in the various studies outlined in this update. PMID- 1453913 TI - Diagnosis of bacterial vaginosis in a routine diagnostic laboratory. AB - Vaginal swabs from 299 hospital and general practitioners' patients were examined for Gardnerella vaginalis by Gram film and by culture, G. vaginalis was isolated in 12% of cultures. Comparison between the 'clue' cell and culture methods suggested that the former is a rapid, acceptable routine screening method for the detection of G. vaginalis. The value of the traditional method of identifying G. vaginalis by sensitivity testing is questioned. All specimens were also examined by Gram film and culture, for the presence of Mobiluncus spp, which was detected in 8.4% of specimens by Gram film but only 0.7% by culture. From a questionnaire returned by 84% of clinicians, metronidazole was found to be the most commonly used antimicrobial agent for the treatment of G. vaginalis, and in all but one case appeared to be clinically effective. PMID- 1453915 TI - The ethics of screening for malignant diseases. PMID- 1453914 TI - Serum low density lipoprotein separation: a simple procedure. AB - Reference methods for serum low density lipoprotein (LDL) separation are time consuming and the salts used in density-gradient ultracentrifugation may cause chemical and/or immunological changes in the lipoprotein structure. A method has been developed to provide native LDL suitable for chemical and immunochemical studies. The three step procedure involves firstly the separation of very low density lipoproteins by non-density adjusted ultracentrifugation, secondly the separation of low from high density lipoproteins by LDL precipitation with PEG 6000, and finally the re-dissolution of the pellet in NaCl 150 mmol/l. The effectiveness of LDL separation, as well as the preservation of the electrophoretic mobility of the LDL molecules, was verified by electrophoresis in agarose gel, and the maintenance of the immunochemical reactivity of apolipoprotein B was verified by an immunochemical assay. PMID- 1453916 TI - Clinical and laboratory waste. PMID- 1453917 TI - Democracy and the computer in America. PMID- 1453918 TI - The family-oriented computerized medical record. PMID- 1453919 TI - Does malpractice make Medline mandatory? PMID- 1453920 TI - Delivering x-ray images on hospital computer networks. PMID- 1453921 TI - E-mail for Novell networks from down under. PMID- 1453922 TI - Uncertainty and critical incidents. PMID- 1453923 TI - The ninth annual medical hardware and software Buyers' Guide. PMID- 1453924 TI - Expression and characterization of the cloned Salmonella typhimurium enterotoxin. AB - Earlier, our laboratory reported the cloning of a chromosomally encoded cholera toxin (CT)-like enterotoxin gene from Salmonella typhimurium Q1 into pBR322. Cell lysates from the plasmid clone pC1, containing a 4.8 kb EcoR1 DNA fragment from Salmonella, caused elongation of Chinese hamster ovary (CHO) cells and this biologic activity was neutralized by anti-CT. However, this cloned gene product did not elicit fluid secretion in the rabbit intestinal loop (RIL) model, because of poor expression. We report here, subcloning of a 4.8 kb EcoRI and a 2.7 kb HindIII/Eco Rl fragment into a high expression T7 RNA polymerase/promoter system. Cell lysates from these clones elicited fluid secretion in the RIL model, caused firm induration in rabbit skin and elongated CHO cells. These biological activities were neutralized by anti-CT. SDS-PAGE and subsequent fluorographic analysis of Escherichia coli, harboring recombinant plasmids in a T7 expression system, revealed the presence of two prominent 35S-labeled polypeptides of 25 and 12 kDa, which were immunoprecipitated with anti-CT. The enterotoxin appeared to be 125 kDa in size, based on chromatography on a P-300 column, had a pl of 6.6 to 6.8, and was heat-labile (60 degrees C/5 min). Unlike cloned CT and heat-labile enterotoxin (LT-l), which were localized in the periplasm, the Salmonella enterotoxin was cytoplasmic in nature. PMID- 1453925 TI - Deposition of circulating streptococcal lipoteichoic acid in mouse tissues. AB - The tissue binding properties of streptococcal lipoteichoic acid (LTA) were studied using normal and passively immunized BALB/c mice. After intraperitoneal injection in non-immunized mice, 3H-LTA concentrations in blood, heart, kidney and liver were highest between 24 and 30 h post-injection. LTA deposits in heart remained high for the next 24 h, whereas other tissue levels decreased. Constant amounts of 3H-LTA were detected in urine throughout the 48 h period. In passively immunized mice, the amount of tissue deposition of 3H-LTA was inversely proportional to the ratio of antibodies to LTA. Autoradiography revealed focal deposits of 3H-LTA in heart, kidney and liver. These observations indicate that LTA, released by streptococci growing at remote body sites, can be carried by the blood to internal organs where it can accumulate and participate in pathogenesis. PMID- 1453926 TI - Growth phase and SpvR regulation of transcription of Salmonella typhimurium spvABC virulence genes. AB - The 90 kb virulence plasmid of Salmonella typhimurium is required for bacterial growth beyond the small intestine to deeper tissues such as the spleen and liver of orally inoculated mice. We constructed transcriptional lacZ fusions within the cloned plasmid-borne virulence genes spvA, spvB and spvC of S. typhimurium to demonstrate that spvR encodes a trans-acting positive regulator for the transcription of spvA, spvB and spvC. Data suggesting that the activation of spvABC transcription is dependent on the growth phase of both S. typhimurium and Escherichia coli grown in Luria Broth (LB) are also presented. Complementation experiments for virulence in mice confirmed that at least spvR and spvC are virulence genes and further suggested that the spvRABC gene cluster consists of at least three transcriptional units containing spvR, spvC and spvABC, respectively. Reinitiation of transcription at spvC was confirmed in vitro, using a lacZ fusion, and was shown to be independent of SpvR-mediated control in LB. PMID- 1453928 TI - Genetic control of resistance to enterotoxigenic Escherichia coli in infant mice. AB - DBA/2 and CBA infant mice orally challenged with bovine enterotoxigenic Escherichia coli (ETEC) strain B80 presented resistance and susceptibility respectively, as measured by mortality rates 6 days after inoculation. Serum antibodies agglutinating ETEC strain B80 had very low titers in both mouse strains. Mendelian analysis of resistance on F1 and on segregating back-crosses showed that resistance is genetic and dominant. Dominance may be explained either by a mixed control with an overdominant major gene or by a polygenic control with a large heterosis effect. PMID- 1453927 TI - Modulation of surface antigen expression by Klebsiella pneumoniae in response to growth environment. AB - Growth in pooled human body fluids [urine, serum and peritoneal dialysate (HPD)] modulated the expression of cell envelope antigens in virulent (serotype O1:K1) and avirulent (serotype O1:K66) Klebsiella pneumoniae strains. Marked variations in the outer membrane protein (OMP) and lipopolysaccharide (LPS) profiles were noted when broth-grown cells were compared with those of bacteria cultured in body fluids. In particular, for the O1:K1 serotype strain, growth in the latter resulted in: (a) the expression of at least five iron-regulated OMPs in the 74-87 kDa range, the pattern of which was medium dependent; (b) alterations in the migration of the LPS core polysaccharide; and (c) the reversion of isogenic O-:K+ and O-:K- mutants to the O+ phenotype after growth in fresh serum but not in heat inactivated serum, urine or HPD. Similar results were obtained for the O1:K66 serotype, although no variation in the migration of the LPS core was noted. For both O1:K1 and O1:K66 serotypes, neither the surface exposure of O1 serotype LPS nor the production of K-antigen (capsular polysaccharide) was affected by growth in body fluids. No reversion of K- mutants to the K+ phenotype was observed. These data illustrate the phenotype flexibility of this opportunistic pathogen and emphasise the crucial role of the O- rather than the K-antigen in protecting K. pneumoniae from complement-mediated serum killing. PMID- 1453929 TI - Transcription analysis and nucleotide sequence of tox promoter/operator mutants of corynebacteriophage beta. AB - The production of diphtheria toxin (DT) by Corynebacterium diphtheriae C7 (beta) is transcriptionally regulated by the iron-dependent diphtheria toxin repressor, DtxR. Transcription of the tox gene was studied in wild-type C. diphtheriae C7 (beta) and in lysogens carrying mutants of beta that determine insensitivity to inhibition of DT production by iron. Under low iron conditions in all strains, tox-specific mRNA appeared and DT production began during late-log phase, and they increased to maximal levels at stationary phase. Under high iron conditions, tox-specific mRNA and DT production were strongly repressed in C7 (beta) but only partially repressed in C7 (beta tox-202) and C7 (beta tox-201). Under high and low iron conditions, DT production and tox-specific mRNA levels were greater in C7 (beta tox-201) and C7 (beta tox-202) than in wild-type C7 (beta). Addition of iron or rifampicin to low iron cultures of C. diphtheriae C7 (beta) repressed tox mRNA production promptly and with a similar time course. In contrast, repression of tox-mRNA synthesis in C. diphtheriae C7 (beta tox-201) occurred promptly after addition of rifampicin but more slowly after addition of iron. Nucleotide sequence analysis revealed single G to A mutations at positions -47 and -48, within the preferred '-10' sequence of the tox promoter, in beta tox-201 and beta tox-202, respectively. The single nucleotide substitutions in the tox-201 and tox 202 regulatory alleles, therefore, have pleiotropic effects, causing increased activity of the promoter and partial resistance of the operator to iron-dependent repression. PMID- 1453930 TI - Physiologic alteration of fibrinogen levels: influence upon patency of microvenous anastomoses. AB - High baseline levels of plasma fibrinogen have been correlated with increased risk for cardiovascular disease. Since fibrinogen plays a central role in both coagulation and platelet aggregation and is a primary component of thrombi, this study was designed to assess the relationship of circulating fibrinogen concentration and vein anastomotic patency. Subcutaneously injected turpentine was used to increase, and intravenous ancrod (snake venom) to decrease, plasma fibrinogen levels. Rat femoral vein anastomoses were performed, and patency was assessed after 120 min of flow. Rat tail bleeding times were obtained, and blood samples were drawn to determine fibrinogen and plasma protein concentrations, Lee White clotting times, and activated partial thromboplastin times (APTT). Increased patency was found in the ancrod group (88%) (P < 0.05 vs. controls); turpentine-treated and control groups were not significantly different (71% and 63%, respectively). The ancrod group also showed significantly prolonged tail bleeding times and APTT. Fibrinogen levels were significantly decreased in the ancrod group (1.73 mg/ml) and elevated in the turpentine group (4.91 mg/ml) vs. controls (2.34 mg/ml; P < 0.005). These results indicate that elevated fibrinogen levels, in particular when triggered by an acute-phase response, do not appear to predispose small vessel repairs toward thrombosis. Furthermore, this study supports the use of ancrod as an anticoagulant for microvascular surgery. PMID- 1453931 TI - Modified anastomotic technique for 1 millimeter internal diameter polytetrafluoroethylene arterial grafts in the rat. AB - Reported patency rates after standard end-to-end anastomoses for microvascular prosthetic grafts have been inconsistent and usually disappointing. A modified anastomotic technique is described in which the prosthetic graft is invaginated inside the arterial lumen. In this study of 6 cm lengths of 1 mm internal diameter polytetrafluoroethylene femoro-femoral bypass grafts in the rat, 6 (40%) of 15 grafts with standard anastomoses were patent at 6 months compared to 28 (90%) of 31 grafts using the modified anastomotic technique (P < 0.001). With invagination of the prosthetic graft inside the arterial lumen, reliable high patency rates can be achieved with microvascular prostheses long enough for potential clinical applications. PMID- 1453932 TI - Long-term results of 1 millimeter arterial anastomosis using the 3M precise microvascular anastomotic system. AB - The 3M Precise Microvascular Anastomotic System has been tested experimentally in long-term studies of arteries of 1 mm in diameter for the first time. The device was placed, using a newly described technique, in the infrarenal aorta of 25 rats. At different intervals (2 weeks, 16 weeks, and 1 year), the section containing the 3M Precise Microvascular Anastomotic System was removed and processed for light microscopy and scanning electron microscopy. All the anastomoses were found to be patent. Using a new device to process the material, both light microscopy and scanning electron microscopy at 2 weeks showed a perfect reparative process at the junction site and the presence of a continuous endothelial layer. Media atrophy was responsible for wall thinning within the device. At 16 weeks, the atrophy of the media was even more marked, reducing the vessel wall thickness within the device to one-third of normal. At 1 year, this atrophy of the media was complete; smooth muscle cells disappeared and were replaced by fibrous tissue. Adventitia was not present over the long term within the device. The continuous endothelial layer, however, was still viable. These long-term results suggest that scar tissue forms within the device, while a continuous endothelial layer remains viable internal to this. PMID- 1453933 TI - Use of fibrin glue to minimize bleeding of microvascular repairs in hypertensive rats. AB - The purpose of this study is to describe our technique of applying fibrin glue at the microvascular anastomotic site and to evaluate the effect of fibrin glue on anastomotic hemostasis and patency under various high pressure states using dopamine-induced acute hypertension in rats. A total of 72 male Wistar Kyoto rats, 10 weeks old, were used in this study. Under urethane anesthesia, end-to end anastomosis of the left femoral artery was performed using 10-0 nylon suture by the standard interrupted suture technique. Pasteurized fibrin glue was then topically applied upon the suture line of the anastomosis. Thirty-six normotensive rats were divided into three groups based on the number of sutures (4, 6, or 8) used to complete the anastomosis. Groups were subdivided, half receiving fibrin glue application and half without. Thirty-six dopamine-induced acutely hypertensive rats were divided into three groups based on the blood pressure levels of 150, 200, and 250 mmHg, respectively. These groups were again subdivided, with half receiving glue applications. Microvascular anastomosis was performed using 6 nylon sutures. Patency rates and anastomotic bleeding were evaluated. The results revealed that successful anastomoses could be performed with fewer sutures when fibrin glue was used as a reinforcement at the anastomosis. Fibrin glue was also effective at the maximum blood pressure (250 mmHg) with no anastomotic leakage and no decrease in postoperative patency rate. These results suggest that conventional microsurgical suturing technique combined with fibrin glue would be effective in the prevention of leakage in microsurgical repairs, even under conditions of high blood pressure. PMID- 1453934 TI - Development of a new rabbit ear model for the longitudinal study of digital pathophysiology. AB - A rabbit ear model has been developed in which arterial pressure, auricular blood flow conductance, and microvascular perfusion can be followed continuously in conscious animals. Conductance is measured with a transit-time flow probe placed around the auricular artery, arterial pressure is measured with an abdominal aortic catheter, and cutaneous microvascular perfusion is assessed using laser Doppler fluxmetry. Placement of a femoral vein catheter permits administration of vasoactive substances. To date, rabbits have been instrumented for 90 days or longer. Auricular and abdominal arterial pressures were equal, permitting the calculation of auricular artery conductance. Microvascular perfusion as measured by laser Doppler fluxmetry followed changes in overall blood flow. The presence of postsynaptic alpha 2-receptors was confirmed by determining auricular conductance before and after the administration of intravenous alpha-agonists. The development of this unique model will help to advance the understanding of the pathophysiology of human digital thermoregulatory vascular abnormalities. PMID- 1453935 TI - Microsurgical approach to the abdominal thoracic duct in the rat: considerations in the collection of lymphocytes. AB - In experiments involving the collection of thoracic duct lymphocytes the anatomy of the abdominal thoracic duct in the rat has been further defined. In general, the abdominal thoracic duct lies posterior and to the left of the aorta between the renal arteries and the diaphragm. There are variations in the microsurgical approach to the classically described location of this organ that should be noted by investigators attempting to identify and dissect this structure. PMID- 1453936 TI - Variability of venous anatomy of rat testis: application to experimental testicular surgery. AB - The venous drainage of the testis of the laboratory rat was observed in 31 animals. The right testicular (internal spermatic) vein drained directly into the right common iliac vein in 77.4%, and into the inferior vena cava in 22.6% of the animals. The left testicular vein drained into the left common iliac vein in all animals, but in 90.3% there was also an accessory branch of the testicular vein draining into the left renal vein. These observations suggest that in the rat the exact anatomy of the venous drainage of each testis should be identified prior to undertaking any surgical procedure on the testis where the venous vasculature plays a major role such as testicular transplantation or the creation of an experimental varicocele. PMID- 1453937 TI - Thigh adductor flap: an experimental model for free flap transfer in the rat. AB - A new model of rat muscle free flap transfer is presented. The flap is based on a long pedicle originating from the femoral vessels and continuing down to the distal saphenous margin at the ankle. The distal portion of the semitendinosus muscle is harvested along with the saphenous artery and great saphenous vein. A larger muscle flap may be harvested by including the distal portions of the posterior and anterior gracilis muscles. The flap can be transferred to remote sites on the animal, with a vascular pedicle of up to 3 cm in length. The diameters of the vessels repaired are of standard microsurgical size. This model has distinct advantages of simplicity, speed of dissection, high success rate after microvascular transfer, and versatility in placement of the muscle mass (due to the long pedicle). PMID- 1453938 TI - New rapid technique for renal transplantation in the rat. AB - Present techniques for renal transplantation in the rat include a period of 20-25 minutes warm ischemia. Our method combines a recently described sleeve anastomotic technique for the renal artery, conventional end-to-end anastomosis of the renal vein, and implantation of the ureter into the bladder. This has resulted in a reproducible ischemic interval of 12-14 minutes. Plasma creatinine and histological features in animals sacrificed from 10 to 30 days after transplantation were within normal limits with no evidence of ischemic damage. A further advantage of the technique is that kidneys can be exchanged between the donor and recipient. It is recommended that this procedure, which reduces the ischemic interval by up to 50%, should be learned and employed in studies of renal transplantation in the rat, especially if such studies include the prior administration of cyclosporine, which may aggravate the effects of ischemia. PMID- 1453939 TI - Small bowel transplantation in the mouse: development of a model. AB - The rat has been used as a model to study the significance of graft and host interactions in small bowel transplantation (SBTX). A mouse model of SBTX would allow investigators to apply the knowledge of the well-defined genetics in the mouse to this field of study. Therefore, we have developed a mouse model of heterotopic SBTX using syngeneic C57BL6/J mice. Animals were anesthetized with a combination of ketamine and xylazine. Donor animals underwent midline laparotomy, with isolation of a segment of bowel as an isograft for transplantation to a recipient animal. The bowel was flushed in situ prior to removal of the graft with a Carrel patch of aorta and portal vein. The recipient animal underwent midline laparotomy and preparation of its infrarenal aorta and inferior vena cava for end-to-side anastomosis of the graft with 10-0 nylon. After vascular reperfusion of the graft the ends of the isografted bowel were brought out as stomata. Successful grafts were later assessed for viability by laparotomy or histological examination at the time of sacrifice. Areas of technical difficulty in this model and issues that might improve the experimental results are discussed. This model should allow investigators to apply the well-defined genetics of the mouse to probe the challenging field of intestinal transplantation. PMID- 1453940 TI - Free flap failure due to venous occlusion secondary to previous intravenous cannulation: a case report. AB - A case of failure of a free radial forearm flap is presented. It is surmised that this was due to venous thrombosis in the cephalic vein which showed evidence of recanalization of an old thrombus. The patient had received intravenous erythromycin some months previously. PMID- 1453941 TI - [Prof. Waclaw Henryk Markert (1898-1992)]. PMID- 1453942 TI - [New approach to the system of training of medical professionals in the realization of current objectives with regard to workers' health care]. AB - In view of the changes in the health care for workers, there is a need to modify the existing system of training for occupational health care professionals in order to secure successful implementation of the new principles. An activity was undertaken at the Postgraduate Training Unit, Institute of Occupational Medicine, Lodz, Poland, to determine new directions, objectives and training curricula in that area. First proposals, based on the review of the new objectives of the occupational health care system and of the presently available staff, concentrate on the indication of three major groups of professionals for which the new training contents should be designed. These three groups include: occupational health care organizers, public health experts and physicians specializing in specific health care for industrial workers. PMID- 1453943 TI - [A computerized system for the protection of the hearing of workers exposed to noise]. AB - The periodical audiometric examinations carried out in order to identify persons with high susceptibility to acoustic trauma is very important in the hearing protection projects concerning workers occupationally exposed to noise. The authors present a computerized system which allows collection and analysis of the results of medical and audiometric examinations. Computer analysis of audiometric data helps to select and protect the workers with dynamic progression of hearing impairment. We believe that the hearing protection system we propose may improve medical care for the workers at risk. PMID- 1453944 TI - [Effects of selected factors on the degree of psychomotor efficiency of welders in a railroad car factory with automated work stations (robots)]. AB - The study of 64 welders employed at automated work stands in the railway car factory conducted in 1989 and 1990 has shown that the psychomotor efficiency level in the examined workers (except for a few cases) was normal. The psychomotor efficiency of the welders studied depended on their age, work day phase and, to a small degree, on the detected biochemical and toxicological disorders. PMID- 1453945 TI - [Changes in the levels of tissue polypeptide antigen and carcinoembryonic antigen in the blood of workers exposed to aromatic amines]. AB - The tissue polypeptide antigen (TPA) and carcinoembryonal antigen (CEA) are the markers used for screening and treatment monitoring of the bladder cancer. A study was carried out in a group of 38 workers chronically exposed to aromatic amines in a dye factory. The findings were compared with those of he study on CS2 exposure and for the non-exposed workers. The results revealed a statistically significant differences between TPA values in the exposed and non-exposed workers. This finding does not apply to CEA. No significant differences between the markers' values were found in the group of workers exposed to CS2. The highest percentage of abnormal values, 29.2%, refers to the workers with a low acetylation phenotype; taking into account the smoking habit the TPA value would amount to 102 U/L in the smokers and to 64.8 U/L in the non-smokers. The studies indicate the higher usefulness of TPA as a marker of the effects of exposure to aromatic amines than that of CEA. PMID- 1453946 TI - [Immunological profile of workers occupationally exposed to chlorine]. AB - Immunological profile of 42 men working under exposure to chlorine for a period from 2 to 38 years was analysed. Toxicological analyses of air samples which were carried out for 20 years showed similar chlorine concentration ranging from 0.21 to 1.05 mg/m3. The number of B, T, and non-B, non-T lymphocytes was determined as well as the C3c, C4 complement components and proteins of acute phase reaction: alpha 1-acid-glycoprotein, haptoglobin and ceruloplasmin in the serum. Chronic exposure to chlorine produced a stimulating effect on the immune system, which was manifested by elevated IgA, IgD and IgM levels, the concentration of acute phase reaction proteins and increased number of B lymphocytes. The observed phenomenon had no influence on the antibacterial and anticancer immunity of the workers. PMID- 1453947 TI - [Chronic bronchitis and respiratory capacity of the lungs in miners from a specific coal mine]. AB - In the group of 3317 miners of one coal mine, who were employed for over 8 years, the prevalence of chronic bronchitis (ch.b.) and lung ventilation disorders was analysed. The frequency of ch.b. in the subjects under study was almost twice as high as in the general male population in Poland and significantly more frequent in miners with pneumoconiosis than in those without pneumoconiosis. Simple pneumoconiosis and ch.b. contributed to decreased ventilatory capacity of the lung. PMID- 1453948 TI - [Evaluation of the immune system in workers engaged in the production of coal derivatives]. AB - The study involved 361 people, 161 of whom were workers of coke plants and the remaining 200 constituted the control group. The coke plant workers were divided into the exposed and non-exposed groups. All of them were subject to the following tests: rosette test, determination of B lymphocytes, determination of the concentration of IgG, IgA, IgM immunoglobulins, and NBT granulocyte reduction test only were found in group I. Subgroups Ia, IIa, IIIa were established, in which subpopulations of T, TH-helper, TS-suppressor, TH and NK (Natural Killer) lymphocytes were discovered in group Ia. The above observations can probably be associated with exposure to tar substances which contain pyrenes. PMID- 1453949 TI - [Morbidity among workers exposed to lead--review of epidemiological studies]. AB - The paper presents a review of morality studies for workers occupationally exposed to lead. The authors highlighted the limitations which most of the reviewed analyses suffer from and which are due mainly to incomplete characteristics of the exposure in question. As follows from the results of morality studies carried out so far, lead-exposed workers are subject to an increased risk of death from stomach and lung cancer, though the epidemiologic evidence for the latter is not quite explicit. The single reports on the risk of cerebrovascular diseases probably concerns only the high-level exposure. Relatively best documented is the death risk due to nephritis. The authors believe that further research is necessary in order to evaluate delayed health effects of chronic exposure to lead. PMID- 1453950 TI - [An atypical case of acute zinc poisoning]. AB - The paper discussed a case of acute zinc intoxication in a 48-year old welder, after four days of cutting zinc-plated pipes with an oxy-acetylene torch, in poorly ventilated places. The zinc fever has been diagnosed on the basis of the symptoms and confirmed by laboratory findings: high zinc blood and erythrocyte concentration and increased urinary excretion of zinc. One year the intoxication the manifestations of the psycho-organic syndrome with predilection to pseudoneurotic reactions were still present. The non-standard factor in this case is the very short time of exposure to zinc oxide and the occurrence of chronic encephalopathy is also singular. PMID- 1453952 TI - Use of a cis-acting mutation to study the role of FLP-mediated recombination in the maintenance of native yeast 2 micrometer plasmids. AB - The 2 micrometer plasmid encodes a mechanism that ensures the partitioning of the plasmid at cell division. Little is known about the detailed mechanism of this partitioning system; for example, is there equal or unequal distribution of the plasmid molecules at mitosis? The plasmid also encodes a site-specific recombination system that is thought to be involved in plasmid copy-number amplification, although to date there has been no direct evidence that the recombination process itself is important for maintenance. We have identified a natural 2 micrometer variant that has a cis-acting mutation in the FLP-mediated recombination system. We show that this plasmid is unable to amplify in vivo. Our results demonstrate that the average copy number per cell is not affected for the mutant but there is a large clonal variation. This is a direct demonstration that plasmid partitioning results in an unequal distribution of plasmids and that FLP mediated amplification compensates for this and therefore has an important role in maintenance. PMID- 1453951 TI - Molecular characterization of the trypanothione reductase gene from Crithidia fasciculata and Trypanosoma brucei: comparison with other flavoprotein disulphide oxidoreductases with respect to substrate specificity and catalytic mechanism. AB - Trypanothione reductase belongs to the family of flavoprotein disulphide oxidoreductases that include glutathione reductases, dihydrolipoamide dehydrogenases and mercuric reductases. Trypanothione reductase and its substrate, trypanothione disulphide, are unique to parasitic trypanosomatids responsible for several tropical diseases. The crystal structure of the enzyme from Crithidia fasciculata is currently under investigation as an aid in the design of selective inhibitors with a view to producing new drugs. We report here the cloning and sequencing of the genes for trypanothione reductase from C. fasciculata and Trypanosoma brucei. Alignment of the deduced amino acid sequences with 21 other members of this family provides insight into the role of certain amino acid residues with respect to substrate specificity and catalytic mechanism as well as conservation of certain elements of secondary structure. PMID- 1453953 TI - DNA sequence determination and functional characterization of the OCT-plasmid encoded alkJKL genes of Pseudomonas oleovorans. AB - The alkBFGHJKL and alkST operons encode enzymes that allow Pseudomonas putida (oleovorans) to metabolize alkanes. In this paper we report the nucleotide sequence of a 4592 bp region of the alkBFGHJKL operon encoding the AlkJ, AlkK and AlkL polypeptides. The alkJ gene encodes a protein of 59 kilodaltons. The predicted amino acid sequence shows significant homology with four flavin proteins: choline dehydrogenase, a glucose dehydrogenase and two oxidases. AlkJ is membrane-bound and converts aliphatic medium-chain-length alcohols into aldehydes. The properties of AlkJ suggest that it is linked to the electron transfer chain. AlkJ is necessary for growth on alkanes only in P. putida alcohol dehydrogenase (AlcA) mutants. AlkK is homologous to a range of proteins which act by an ATP-dependent covalent binding of AMP to their substrate. This list includes the acetate, coumarate and long-chain fatty acid CoA ligases. The alkK gene complements a fadD mutation in Escherichia coli, which shows that it indeed encodes an acyl-CoA synthetase. AlkK is a 60 kilodalton protein located in the cytoplasm. AlkL is homologous to OmpW, a Vibrio cholerae outer membrane protein of unknown function, and a hypothetical polypeptide encoded by ytt4 in E. coli. AlkL, OmpW and Ytt4 all have a signal peptide and end with a sequence characteristic of outer membrane proteins. The alkL gene product was found in the outer membrane of E. coli W3110 containing the alk-genes. The alkL gene can be deleted without a clear effect on growth rate. Its function remains unknown. The G+C content of the alkJKL genes is 45%, identical to that of the alkBFGH genes, and significantly lower than the G+C content of the OCT-plasmid and the P. putida chromosome. PMID- 1453954 TI - Molecular and symbiotic characterization of exopolysaccharide-deficient mutants of Rhizobium tropici strain CIAT899. AB - We studied the symbiotic behaviour of 20 independent Tn5 mutants of Rhizobium tropici strain CIAT899 that were deficient in exopolysaccharide (EPS) production. The mutants produced non-mucoid colonies, were motile, grew in broth cultures at rates similar to those of the parent, and produced significantly less EPS than did CIAT899 in broth culture. A genomic library of strain CIAT899, constructed in pLA2917, was mobilized into all of the mutants, and cosmids that restored EPS production were identified. EcoRI restriction digests of the cosmids revealed nine unique inserts. Mutant complementation and hybridization analysis showed that the mutations affecting EPS production fell into six functional and physical linkage groups. On bean, the mutants were as efficient in nodulation and as effective in acetylene reduction as strain CIAT899, induced a severe interveinal chlorosis, and all but one were less competitive than CIAT899. On siratro, CIAT899 induced nodules that were ineffective in acetylene reduction, whereas the EPS-deficient mutants induced effective nodules. Microscopic examination of thin sections showed that nodules from both siratro and bean plants inoculated with either CIAT899 or an EPS-deficient mutant contained infected cells. These data indicate that EPS is not required for normal nodulation of bean by R. tropici, that it may contribute to competitiveness of R. tropici on bean, and that the loss of EPS production is accompanied by acquisition of the ability to reduce acetylene on siratro. PMID- 1453955 TI - A novel transcriptional regulation mechanism in the flagellar regulon of Salmonella typhimurium: an antisigma factor inhibits the activity of the flagellum-specific sigma factor, sigma F. AB - We have studied the molecular mechanism of the negative regulation by flgM of the late operons of the flagellar regulon of Salmonella typhimurium. A 7.8 kDa protein that was identified as the flgM gene product was purified to homogeneity; its amino-terminal sequence was identical to the deduced sequence except for the lack of the initiating methionine. The purified FlgM repressed transcription from the fliC promoter, one that is activated by the sigma factor, FliA (sigma F). No DNA-binding activity was detected in FlgM. Chemical cross-linking experiments showed that the purified FlgM bound to sigma F and disturbed its ability to form a complex with RNA polymerase core enzyme. These results indicate that FlgM is a novel type of negative regulator that probably inactivates the flagellum-specific sigma factor through direct interaction, i.e. it is an anti-sigma factor. PMID- 1453956 TI - A putative anaerobic coproporphyrinogen III oxidase in Rhodobacter sphaeroides. II. Analysis of a region of the genome encoding hemF and the puc operon. AB - The puc operon of Rhodobacter sphaeroides encoding polypeptides of the major light-harvesting complex, LH2, has been found to be linked to hemF, a gene encoding a putative anaerobic coproporphyrinogen III oxidase. The puc-hemF region of the R. sphaeroides genome has been investigated by insertional mutagenesis, complementation analysis of these insertional mutants and DNA sequencing. A third gene, designated pucC, has been found immediately downstream of pucA and has been shown to be essential for LH2 expression. pucC is cotranscribed with pucB and pucA; however, hemF and the pucBAC operon were found not to be transcriptionally linked. Ultrastructural studies indicated that the morphology of the intracytoplasmic membrane may depend upon expression of pucC as well as pucBA. PMID- 1453957 TI - Cloning, mapping and nucleotide sequencing of a gene encoding a universal stress protein in Escherichia coli. AB - The response of non-differentiating bacteria to nutrient starvation is complex and includes the sequential synthesis of starvation-inducible proteins. Although starvation for different individual nutrients generally provokes unique and individual patterns of protein expression, some starvation stimulons share member proteins. Two-dimensional polyacrylamide gel electrophoresis revealed that the synthesis of a small (13.5 kDa) cytoplasmic protein in Escherichia coli was greatly increased during growth inhibition caused by the exhaustion of any of a variety of nutrients (carbon, nitrogen, phosphate, sulphate, required amino acid) or by the presence of a variety of toxic agents including heavy metals, oxidants, acids and antibiotics. To determine further the mode of regulation of the protein designated UspA (universal stress protein A) we cloned the gene encoding the protein by the technique of reverse genetics. We isolated the protein from a preparative two-dimensional polyacrylamide gel, determined its N-terminal amino acid sequence, and used this sequence to construct a degenerate oligonucleotide probe. Two phages of the Kohara library were found to contain the gene which then was subcloned from the DNA in the overlapping region of these two clones. The amino acid sequence, deduced from the nucleotide sequence of the uspA gene, shows no significant homology with any other known protein. The uspA gene maps at 77 min on the E. coli W3110 chromosome, and is transcribed in a clockwise direction. The increase in the level of UspA during growth arrest was found to be primarily a result of transcriptional activation of the corresponding gene. The induction was independent of the RelA/SpoT, RpoH, KatF, OmpR, AppY, Lrp, PhoB and H-NS proteins during stress conditions that are known to induce or activate these global regulators. The -10 and -35 regions upstream of the transcriptional start site of the uspA gene are characteristic of a sigma 70-dependent promoter. PMID- 1453958 TI - Some of the out genes involved in the secretion of pectate lyases in Erwinia chrysanthemi are regulated by kdgR. AB - The out genes of Erwinia chrysanthemi are required for the translocation across the outer membrane of pectate lyases and cellulases. We present the characterization and the nucleotide sequence of five genes of the out cluster. The products of outS, B, C, D and E have significant homology with the PulS, B, C, D and E proteins necessary to the secretion of pullulanase in Klebsiella pneumoniae. An open reading frame, outT, located between outB and outC has no homology with the pul cluster but is involved in secretion. outC, outD and outE form an operon while outS, outB and outT constitute independent transcription units. outT and the outCDE operon are regulated by kdgR, the negative regulatory gene controlling pectinase production. outB and outS seem to be expressed constitutively. PMID- 1453959 TI - Molecular rearrangement of lactose plasmid DNA associated with high-frequency transfer and cell aggregation in Lactococcus lactis 712. AB - High-frequency conjugation of the lactose plasmid pLP712 is associated with a constitutive cell aggregation phenotype and is facilitated by cointegration with a sex factor. Analysis of 23 independently derived enlarged lactose plasmids revealed that the sex factor DNA present in cointegrates varied in size. This suggested that more than simple cointegration with a sex factor plasmid was involved. Further analysis led to the discovery of a chromosomally located sex factor that could excise and be lost or exist as labile plasmid DNA. Cointegration with this sex factor was shown to be promoted by transposition of a copy of ISSI present on the lactose plasmid, and models are presented to account for the complex and variable structures of the resulting enlarged lactose plasmids. PMID- 1453960 TI - The bgl1 gene encoding extracellular beta-glucosidase from Trichoderma reesei is required for rapid induction of the cellulase complex. AB - We have used a targeted gene deletion event to remove the coding region for the bgl1 gene encoding an extracellular beta-glucosidase from the genome of the cellulolytic fungus Trichoderma reesei. The bgl1 null mutants were used to investigate the role of beta-glucosidase in the hydrolysis of cellulose and induction of the other cellulolytic enzyme components. In the absence of extracellular beta-glucosidase, growth of bgl1 null strains on several carbon sources was the same as that of the parent (as measured by mycelial dry weight). However, levels of extracellular protein and total endoglucanase production were seen to lag relative to those levels observed in the control strain. The mRNA levels of the CBHI, CBHII, EGI, and EGII cellulase genes (cbh1, cbh2, egl1 and egl3) showed a corresponding lag in induction, suggesting that the absence of extracellular beta-glucosidase has an effect on the co-ordinate regulation of the other cellulase genes at the level of transcription. The addition of a potent inducer of the cellulase complex (sophorose) resulted in normal rates of cellulase gene mRNA production and extracellular protein release. This indicates that the absence of beta-glucosidase is not affecting some intrinsic cellular ability to produce mRNA or secrete protein. These data suggest that a functional beta-glucosidase is at least partially responsible for the efficient induction of the depolymerase enzymes of the cellulase complex. The observation that the cellulase complex is induced, albeit after a lag, suggests that other enzymes are present that can substitute for the function of beta-glucosidase during induction. PMID- 1453961 TI - Targeted gene replacements in a Streptomyces polyketide synthase gene cluster: role for the acyl carrier protein. AB - A methodology was developed to construct any desired chromosomal mutation in the gene cluster that encodes the actinorhodin polyketide synthase (PKS) of Streptomyces coelicolor A3(2). A positive selection marker (resistance gene) is first introduced by double crossing-over into the chromosomal site of interest by use of an unstable delivery plasmid. This marker is subsequently replaced by the desired mutant allele via a second high-frequency double recombination event. The technology has been used to: (i) explore the significance of translational coupling between two adjacent PKS genes; (ii) prove that the acyl carrier protein (ACP) encoded by a gene in the cluster is necessary for the function of the actinorhodin PKS; (iii) provide genetic evidence supporting the hypothesis that serine 42 is the site of phosphopantetheinylation in the ACP of the actinorhodin PKS; and (iv) demonstrate that this ACP can be replaced by a Saccharopolyspora fatty acid synthase ACP to generate an active hybrid PKS. PMID- 1453962 TI - The HsdS polypeptide of the type IC restriction enzyme EcoR124 is a sequence specific DNA-binding protein. AB - The HsdS and HsdM polypeptides of the type IC restriction enzyme EcoR124 have been purified independently and used in a set of gel retardation experiments to determine the minimum requirements for sequence-specific recognition of DNA by this enzyme. The HsdS polypeptide alone is able to bind to DNA in a sequence specific manner. In addition, whilst the presence of the HsdM polypeptide gives rise to a stimulation of DNA binding by the HsdS subunit it is not clear whether, under the conditions of the experiments reported here, the HsdS subunit maintains the same interactions with the HsdM subunits observed in the absence of DNA. PMID- 1453963 TI - Mental models, pictures, and text: integration of spatial and verbal information. AB - In the past several years, there has been an acceleration in the publication of cognitive research on the interplay between linguistic and pictorial/spatial information. To report on and encourage this sort of research, we organized a symposium at the 1991 meeting of the Midwestern Psychological Association. The articles in this special section of Memory & Cognition are based on the work presented at the symposium. In this introduction, we offer a suggestion for why the integration of linguistic and spatial information is not only a possibility, but a requirement for effective communication. Our suggestion follows the linguistic analysis of the closed-class elements that convey spatial relations, the prepositions (Talmy, 1983). The structure of language provides but a small set of prepositions to encode the vast number of spatial relations that we can perceive. Thus, to understand a situation that a speaker or a writer is conveying, the listener or reader must combine linguistic information with (perhaps metric) spatial information derived from pictures, the environment, or memory. PMID- 1453964 TI - Pictures and anaphora: evidence for independent processes. AB - Pictures enhance our comprehension of written texts, but the perceptual and cognitive processes that underlie this effect have not been identified. Because integrating the information contained in a text places demands on working memory, the effect of a picture may be to expand the functional capacity of working memory and thereby to facilitate comprehension. Reasoning thus, we predicted that the availability of a diagram would interact with the difficulty of resolving anaphoric references in texts. The resolution of an anaphor distant from its antecedent (which should stress working memory) should benefit greatly from the presentation of a picture, whereas the resolution of an anaphor near to its antecedent should benefit less from the presentation of a picture. Picture availability and distance separating the anaphor from its antecedent were manipulated in experiments involving both cumulative and moving window presentations of texts. Although picture presence and ease of anaphor resolution significantly improved comprehension of the material, no evidence was found for an interaction of these factors. The results are interpreted as consistent both with dual code theory and with aspects of working memory management that do not involve anaphor resolution. PMID- 1453965 TI - Pictorial enhancement of text memory: limitations imposed by picture type and comprehension skill. AB - We examined the kinds of information in a prose passage that is better remembered when depictive illustrations are embedded in the passage than when the passage contains no illustrations. Experiment 1 showed that (1) pictures depicting details effectively increased recall of those details and (2) pictures depicting relationships effectively increased recall of that relational information (relative to a no-picture control condition). In Experiment 2, comprehension skill was found to modulate the general effects obtained in Experiment 1. Detail pictures enhanced the recall of targeted details for all skill levels. Relational pictures enhanced recall of pictured relational information for highly skilled and moderately skilled comprehenders, but not for less skilled comprehenders. Because there were no recall differences across the different skill levels in the no-picture control condition, it is suggested that pictures may serve to enable processing in which readers would not necessarily engage under ordinary circumstances. Pictures, however, did not appear to compensate for limitations reflected in lower scores on a standardized test of reading comprehension. PMID- 1453966 TI - Descriptions and depictions of environments. AB - Subjects studied maps with the expectation that they would draw or describe them from memory. In fact, subjects did both. Order of drawing or describing landmarks revealed the mental organization of environments. Organization was quite similar across maps and descriptions of the same environments, revealing hierarchical structures based on spatial and functional features of the environments and on conventions for sequencing the landmarks. PMID- 1453967 TI - Structural properties of visual images constructed from poorly or well-structured verbal descriptions. AB - Previous research has found a linear relation between distance and scanning times for spatial configurations when the spatial configurations were learned perceptually and when they were constructed from well-structured verbal descriptions. The current research replicated the time-distance relation when the images were constructed from repetitions of well-structured descriptions but not when the images were generated from three repetitions of a description that presented information in a random order. Six exposures to the randomly ordered information yielded the expected time-distance relation in image scanning. We posited that additional exposure to the poorly structured information allowed the image to develop the structural coherence and resolution needed to support consistent scanning. Thus, the structure of descriptions can affect the intrinsic structure of images of described objects and hence the mental operations performed subsequently on these images. Another experiment indicated that image coherence and resolution improves even after the verbal description is accurately recalled. PMID- 1453968 TI - Switching points of view in spatial mental models. AB - In six experiments, subjects read narratives describing varying spatial scenes with more than one point of view. They were probed with questions about objects located in six directions from each character's point of view. Subjects' response times were consistent with a one place-one perspective rule. They seemed to form separate mental models for separate places and to take a character's perspective when there was only one relevant character in a scene, but they seemed to take a neutral perspective when there was more than one probed point of view, rather than switch perspectives. PMID- 1453969 TI - The representation and integration in memory of spatial and nonspatial information. AB - A series of experiments investigated whether people could integrate nonspatial information about an object with their knowledge of the object's location in space. In Experiments 1 and 3, subjects learned the locations of cities on a fictitious road map; in Experiments 2, 4, and 5, subjects were already familiar with the locations of buildings on a campus. The subjects then learned facts about the cities on the maps or the buildings on the campus. The question of interest was whether or not these nonspatial facts would be integrated in memory with the spatial knowledge. After learning the facts, subjects were given a location-judgment test in which they had to decide whether an object was in one region of the space or another. Knowledge integration was assessed by comparing levels of performance in two conditions: (a) when a city or a building name was primed by a fact about a neighboring city or building, and (b) when a city or a building name was primed by a fact about a distant city or building. Results showed that responses in Condition a were faster or more accurate, or both faster and more accurate, than responses in Condition b. These results indicate that the spatial and nonspatial information were encoded in a common memory representation. PMID- 1453970 TI - Abstract versus modality-specific memory representations in processing auditory and visual speech. AB - Serial recall of lip-read, auditory, and audiovisual memory lists with and without a verbal suffix was examined. Recency effects were the same in the three presentation modalities. The disrupting effect of a suffix was largest when it was presented in the same modality as the list items. The results suggest that abstract linguistic as well as modality-specific codes play a role in memory for auditory and visual speech. PMID- 1453971 TI - Individual differences in bridging inference processes. AB - The role of individual differences in bridging-inference processing was studied. Students (n = 135) read passages of short to moderate length. After each one, they answered corresponding questions about inferences that bridged causally related ideas that were either near or far apart in the text. The main hypothesis was that local bridging-inference processing is facilitated by the reader's predisposition to access pertinent knowledge during comprehension. Regression analyses provided support for this proposal and indicated that greater working memory capacity and vocabulary knowledge promote inference processing. The following relationships between the predictors and inference processing were proposed: Knowledge access promotes the co-occurrence in working memory of the text ideas and knowledge needed to compute the bridge. Working-memory capacity enhances the likelihood that needed antecedent ideas will be available to the bridging processes. Vocabulary knowledge may promote inference processing because unfamiliar word meanings place more demands on working-memory resources than do familiar meanings. PMID- 1453972 TI - Dissociations among memory measures in memory-impaired subjects: evidence for a processing account of memory. AB - Deficits in conceptual transfer on both implicit and explicit memory tests were obtained for memory-impaired temporal lobe epileptic (TLE) subjects in three studies. In Experiment 1, in which a generate-read paradigm was employed, memory impaired TLEs failed to show normal generation effects on conceptually driven tests of semantic cued recall and general knowledge questions, although their data-driven memory as measured by word-fragment completion and graphemic cued recall tasks was normal. In Experiment 2, memory-impaired patients having left temporal lobe seizure foci were tested on these four tasks and compared with nonimpaired TLEs having right temporal foci. The left TLEs showed deficits on conceptually driven tasks and normal memory for data-driven tests. These findings were extended in Experiment 3, in which left TLE patients failed to show any benefit from blocked study, as compared with random study, on category production and semantic cued-recall tests, although right TLEs and normal controls showed blocking effects on both tasks. These findings may be accommodated by a processing framework of memory in which memory-impaired patients are characterized as having deficits in conceptual, but not in data-driven, processing capabilities. PMID- 1453974 TI - Effect of local context of responding on human judgment of causality. AB - Two experiments examined the effect of various relationships between a response (pressing the space bar of a computer) and an outcome (a triangle flashing on a screen) on judgments of the causal effectiveness of the response. In Experiment 1, when responses were required to be temporarily isolated from each other prior to an outcome, ratings of the causal effectiveness of the responses were higher than in a condition in which the probability of an outcome following a response was the same but in which no temporal isolation was required. In Experiment 2, when a number of responses were required to be emitted temporally close to the outcome, ratings of the causal effectiveness of the responses were lower than in a condition in which the probability of an outcome following a response was the same but in which no temporal proximity was required. These results suggest that, in addition to the overall probability that an outcome will follow a response, the local context of responding at the time an outcome is presented is critical in influencing ratings of causal effectiveness. PMID- 1453973 TI - In search of a strong visual recency effect. AB - When a sequence of visual stimuli is presented in a fixed location, immediate serial recall of the sequence is characterized by only a small recency effect. According to Battacchi, Pelamatti, and Umilta (1990), the distribution of visual stimuli over space, as well as time, greatly enhances the recency effect. After an initial failure to find a strong visual recency effect with distributed presentation (Experiment 1), in the remaining experiments an attempt was made to more closely approximate Battacchi et al.'s methodology by eliminating articulatory suppression (Experiments 2-7), using their stimuli (Experiments 3 7), blocking conditions (Experiments 4-7), requiring written rather than typed responses (Experiments 5-7), and using their list length (Experiments 6 and 7). Nevertheless, even when their method was followed as closely as possible (Experiment 7), distributed presentation did not produce a strong visual recency effect. The influence of distributed presentation on the visual recency effect would seem to be, at best, limited. PMID- 1453975 TI - Cuing effects and associative information in recognition memory. AB - Item recognition requires discrimination of studied words from nonstudied words. Associative recognition requires subjects to discriminate studied word groups from recombinations of words from different groups. Cued recognition requires the same old-new discrimination as item recognition, but list items are presented as cues along with the test item. The results from three experiments show (1) little or no effect of cuing for low-frequency words, but (2) positive cuing effects for high-frequency words; (3) increasing levels of overall performance with increases in study time, but (4) unchanging effects of cuing with study time; and (5) stronger positive cuing effects for two cues than for one cue. Five models (Independent Cue Model, Matrix model, MINERVA 2, SAM, and TODAM) were fit to the data of Experiment 1. Each model has trouble with at least one aspect of the results. Theoretical implications and modifications are discussed at length. PMID- 1453976 TI - Will we ever increase the incidence of breast feeding? PMID- 1453977 TI - Attitudes of Vietnamese women to baby feeding practices before and after immigration to Sydney, Australia. AB - The purpose of this study was to explore Vietnamese women's attitudes, behaviour and beliefs towards baby feeding practices before and after immigration to Sydney. Findings from 70 questionnaires and 20 in-depth face-to-face interviews with ethnic Vietnamese women indicated that Vietnamese women's preference towards baby feeding practices was shaped by their health beliefs, which in turn were influenced by the social, cultural and economic environment of the host country. Changing to bottle feeding was an adaptation process, a bridge between the old and the new environments. Recommendations have been made regarding ways of promoting breast feeding among immigrant women. PMID- 1453978 TI - Systems of midwifery care in use in Scotland. AB - A survey was undertaken to identify the different systems of midwifery care in use in hospital and community settings in Scotland. The 53 units which responded provided 90% of the maternity care in Scotland. Of the 53 units, the 28 integrated units undertook 83% of Scottish births and were more likely than the non-integrated units to have implemented systems designed to reduce fragmentation of care. Nearly a fifth of units had five different systems of care in operation. More than half the units had at least one of the following systems of care in operation or under planning: individualised care plans; 'patient allocation'; DOMINO schemes; nursing/midwifery process or model; and team midwifery. The most frequently used system was planning individualised care (88% of the units). 'Patient allocation', nursing/midwifery process or model and the DOMINO scheme were in over 60% of the units. The least used system was team midwifery, which was in operation in 21% of the units and being planned for a further 30%. The use of the different systems in combination within a number of units demonstrates that approaches to the objective of continuity of care are complex. There is a need for further research into continuity of care as this is a commonly cited advantage of all five systems of care. PMID- 1453979 TI - The impact of research findings on current practice in relieving postpartum perineal pain in a large district general hospital. AB - In order to study the impact of research findings on current clinical practice 100 members of midwifery and medical staff of a large district general hospital were surveyed regarding their treatment of postpartum perineal pain. Of the 76 who responded only 20 (26%) referred to research findings to support their clinical practice and in only one case was the research appropriate to the population in question. Important research findings were not applied, while the majority of the reported practice was not research-based. Research-based practice is not only the responsibility of the individual clinician but also of those at educational and management levels. Local strategies should be developed and resources made available to facilitate research utilisation and implementation. PMID- 1453980 TI - Early postpartum discharge--an alternative to traditional hospital care. AB - In a predictive study of early postpartum discharge data were collected to justify a proposal that was being developed by a city hospital and the Local Board of Health to provide maternity care for women who wished to be discharged early from hospital following childbirth. In this paper the findings of the predictive study are presented and then compared with the findings from the evaluation of the project which was implemented by the hospital and the Local Board of Health. Overall, the findings from the predictive study were accurate when compared to the findings from the evaluation study. The similarity of findings in both studies demonstrates the value of undertaking a predictive study prior to planning changes in delivery of health care to a specific population. PMID- 1453981 TI - A preliminary evaluation of education material prepared for the Safe Motherhood Initiative Educational Project. AB - Maternal death is a tragedy which is all too familiar in much of the world. As part of the Safe Motherhood Initiative the World Health Organization is developing and producing a learning package designed specifically for midwives. Through a modular system of learning incorporating aspects of community, prevention, treatment and follow-up the package seeks to address the five main causes of maternal mortality. In this paper the first pre-testing of the educational material in an African country is described. The extent of the evaluation is limited at this early stage but the initial analysis of the results is encouraging and have led to modifications of the original package. The evaluation has confirmed that a tool such as this package can be a valuable resource for midwife teachers attempting to improve the relevance of education for their midwifery students. The midwifery students whilst being 'with woman' in childbirth are also grappling with the realities of death in their everyday practice. The educational package has also reinforced the sense of urgency fundamental to completing this extensive project so that it can be made available to midwives throughout the developing world at the earliest opportunity. PMID- 1453982 TI - Electrophoretic mobility and immunoblot analysis of the outer membrane proteins of Aeromonas hydrophila, A. sobria and A. caviae. AB - The outer membrane profiles of three species of the genus Aeromonas were examined by means of SDS-PAGE and immunoblotting to identify species-specific polypeptides and antigens which could presumably be applied to differentiate Aeromonas spp. at the species or subspecies level. Profiles on an 11% discontinuous SDS-PAGE showed common band sharing at the 52 kD position. Species-specific bands for the three strains could also be detected. Immunoblots using heterologous LPS-adsorbed polyclonal antisera revealed demarcated common and uncommon antigens within the three species. Outer membrane preparations were immunoblotted against whole cell polyclonal antisera. The previously documented host pathogenicity of A. sobria correlated well with the immunoblots which showed antigenicity, especially due to the LPS, when compared with the other two species. PMID- 1453983 TI - Susceptibility of sixty-five non-oral clinical isolates of the Streptococcus milleri group to seven antimicrobial agents. AB - Antimicrobial susceptibilities of sixty-five non-oral Streptococcus milleri group clinical isolates to penicillin, gentamicin, lincomycin, ampicillin, chloramphenicol, tetracycline and erythromycin were determined by an agar dilution method. All strains were penicillin-sensitive (MIC < or = 0.031 microgram/ml) and the majority (64/65) were susceptible to erythromycin (MIC < or = 0.125 microgram/ml). Low-level resistance to gentamicin was observed, and the majority of strains possessed an MIC of 8 micrograms/ml. Lincomycin and ampicillin at 0.5 microgram/ml inhibited 52/65 and 61/65 strains, respectively. Of the isolates 92% were inhibited by chloramphenicol at < or = 2 micrograms/ml. Twenty-two S. milleri group strains (of which thirteen were vaginal isolates) were resistant to tetracycline (MIC > or = 8 micrograms/ml). PMID- 1453984 TI - beta-N-acetylhexosaminidases from Serratia marcescens. AB - Two forms of beta-N-acetylhexosaminidase from Serratia marcescens with an optimum pH of 5.0 and 6.5, respectively, to 4-methylumbelliferyl-2-acetamido-2-deoxy-beta D-glucopyranoside were separated by DEAE-cellulose chromatography and Sephacryl S 200 chromatography. On the basis of their molecular weights, thermal stability, substrate specificity and isoelectric points, the form with an acidic pH optimum resembled hexosaminidase B, whereas the form with a neutral pH optimum resembled hexosaminidase C. Lectin binding studies showed that the acidic form does not bind to concanavalin-A-Sepharose, Tetragonolobus purpurea-agarose, wheat germ agglutinin-Sepharose or Ricinus communis-agglutinin-agarose, whereas the neutral form binds to the last two lectin columns. PMID- 1453985 TI - Inhibition of the electron transport system in Staphylococcus aureus by trimethylamine-N-oxide. AB - Trimethylamine-N-oxide (TMAO) inhibited the growth of Staphylococcus aureus but not of S. epidermidis, which is the main flora in ripening squid, the Japanese traditional sea food Ika-shiokara. This selective inhibition of S. aureus was based on the inhibition of the electron transport system. The cytochrome fraction isolated from S. aureus was converted from the reduced to the oxidized form by the addition of TMAO. It is suggested that the inhibition occurred between cytochrome B and cytochrome o. PMID- 1453986 TI - The significance of testing for Pseudomonas aeruginosa in recreational seawater beaches. AB - The occurrence of Pseudomonas aeruginosa and faecal coliforms in Mediterranean sea water from beaches was investigated. Water samples (1,598 in toto) were tested and P. aeruginosa was found in 222 samples (14%). In 31% of samples where P. aeruginosa was detected, faecal coliforms of less than ten bacteria per 100 ml were found. In a group of 98 samples which had > 500 faecal coliforms per 100 ml, 41% had no detectable P. aeruginosa. The inclusion of P. aeruginosa as an additional parameter for approving beaches for recreational activity is recommended. PMID- 1453987 TI - In vitro activity of fosfomycin against 'problem' gram-positive cocci. AB - Fosfomycin was active in vitro against 54 of 60 'problem' Gram-positive cocci (20 methicillin-resistant Staphylococcus aureus, 20 coagulase-negative staphylococci and 20 enterococci). Its activity was significantly greater under anaerobic conditions, especially against coagulase-negative staphylococci. Mutants resistant to fosfomycin were readily demonstrated, but their growth was prevented by rifampicin or ciprofloxacin. The combinations rifampicin+fosfomycin and ciprofloxacin+fosfomycin showed MIC synergy. It is concluded that fosfomycin in an appropriate combination would be a valuable addition to the small and dwindling range of antibiotics active against problem Gram-positive cocci. PMID- 1453988 TI - [The comparative characteristics of Vibrio cholerae hemolysins]. AB - Biochemical and biological properties of in vivo and in vitro hemolysins of cholera germs isolated by different authors as well as hemolysins of Vibrio parahaemolyticus and Escherichia coli have been comparatively characterized. According to the above data hemolysin of cholera germ El Tor is a thermolabile protein with molecular mass of 60-80 thou.; it is cytotoxic, enteropathogenic and lyses all the species of erythrocytes. Hemolysins of V. eltor and germs are immunologically related. Hemolysin of the cholera germ is thermostable and has molecular mass of 20-40 thou., that makes it similar to hemolysin of V. parahaemolyticus. PMID- 1453989 TI - [The cloning of fragments of the streptomycete plasmid pSG1912 as a part of the vector pUC19]. AB - DNA fragments of plasmid pSG1912 isolated from Streptomyces globisporus 1912 have been cloned into vector pUC19 in the E. coli cells. Stability of inheritance of hybrid derivatives in enterobacteria has been studied. The clones where recombinant plasmids are stably inherited have been chosen. The detailed restriction maps of cloned DNA fragments of pSG1912 have been constructed. PMID- 1453990 TI - [The properties of cell wall hydrolysates of Streptococcus group A]. AB - Products obtained from lysis in the cell wall of group A streptococcus have been studied in different growth phases: at the end of the exponential phase and in the stationary one. Endo-beta-N-acetylmuramidase extracted from the culture liquid of Streptomyces levoris 96 has been used for lysis of streptococcus. It is stated that streptococcus cell walls isolated at different growth stages differ in the protein and polysaccharide content. High content of protein in the cell wall of a young culture makes lower the initial rate of the walls' hydrolysis by endo-beta-N-acetylmuramidase. However, with the enzyme penetration into peptidoglycan the rate of hydrolysis of cell walls gets higher and after four hour incubation the lysis degree of walls of the 16- and 8-hour cultures reaches the equal value (63%). Studies in the protein composition of lysates of the streptococcus cell walls have shown that they contain at least 12 proteins most of which are acid and neutral ones. PMID- 1453991 TI - [The kinetics of glycol destruction by a Pseudomonas putida BS-2 strain]. AB - Destruction of ethylene glycol and diethylene glycol by Pseudomonas putida BS-2 culture under conditions of its batch cultivation has been studied for its physiological regularities. The specific rate of the biomass growth in the region of limiting substrate concentrations depends on the diethylene glycol concentration in the medium and follows the Mono equation. A semisaturation constant for diethylene glycol is 209 +/- 17 mg/d. The specific rate of the culture growth is independent of the ethylene glycol concentration in the medium within a wide range from 0.08 to 10 g/l. Kinetics of the bacteria growth inhibition by excess of substrates is a complex character and obeys none of the known models of the substrate inhibition. PMID- 1453992 TI - Attitudes to people with disabilities. PMID- 1453993 TI - Women in medicine. PMID- 1453994 TI - Arthritis: the therapeutic challenge. PMID- 1453995 TI - The sale of the Commonwealth Serum Laboratories: wither antivenom research? PMID- 1453996 TI - Deaths from snake bite in Australia, 1981-1991. AB - OBJECTIVE: To obtain and analyse data relating to snake bite fatalities in Australia. DESIGN: Retrospective analysis of case reports and collation of studies carried out at the Commonwealth Serum Laboratories (CSL). RESULTS: 18 deaths attributed to snake bite were reported to CSL over a 10-year period. Eleven of the victims were males and four of these were bitten after either picking up the snake or playing with it. In most cases, no pathological findings of significance were found at autopsy. Venom was detected in post-mortem samples from nine cases. Brown snakes (genus Pseudonaja) were responsible for 11 deaths; tiger snake (Notechus scutatus) for four, taipan (Oxyuranus scutellatus) two and death adder (Acanthophis australis) one. Death after a brown snake bite was often sudden and unexpected. In three patients bitten by tiger snakes and in one bitten by a brown snake, the presence of cerebral haemorrhage was confirmed at autopsy. CONCLUSIONS: Not all snake bite deaths in Australia are adequately investigated or reported. Under some circumstances death from snake bite is almost inevitable; two infants who received unwitnessed massive envenomations are tragic examples. Had venom absorption from the bitten area been delayed by correct first aid, some of the patients might have survived. The brown snakes (genus Pseudonaja) must now be considered Australia's most dangerous group of snakes because their venom may cause sudden unexpected collapse and death. The increased incidence of intracranial haemorrhage may in some cases be related to the intravenous use of adrenaline. In at least one case, the prompt administration of a clearly needed antivenom might have altered the outcome. PMID- 1453997 TI - Quokka bites. The first report of bites from an Australian marsupial. AB - OBJECTIVE: To describe the incidence and natural history of bites from the quokka, a small wallaby. DESIGN: A prospective case series. SETTING: Rottnest Island Nursing Post, a small hospital staffed by registered nurses on call 24 hours a day, located on Rottnest Island 18 km off the coast of Western Australia near Perth. PATIENTS: All patients presenting after a bite from a quokka. RESULTS: Seventy-two patients (30 males and 42 females) presented after a bite. All but two patients were patting or feeding a quokka at the time of being bitten, and all but two were bitten on a finger or the thumb. Sixty-one per cent of patients were followed up; all wounds healed without complications. No wound pathogens were cultured from either wound swabs or swabs of the mouths of quokkas. CONCLUSIONS: Bites from quokkas heal without complications, usually in two to three weeks. Simple first aid and tetanus prophylaxis where appropriate are all that is required. Antibiotics are not indicated. PMID- 1453998 TI - Scombroid poisoning. A report of seven cases involving the Western Australian salmon, Arripis truttaceus. AB - OBJECTIVE: To present the clinical findings of scombroid poisoning due to ingestion of the Western Australian salmon, Arripis truttaceus, occurring in two separate outbreaks involving seven patients. Both outbreaks occurred in March and the fish had been caught in South Australian waters. CLINICAL FEATURES: Onset of symptoms in all patients occurred within half an hour of ingestion of the affected fish. The clinical syndrome included erythema and urticaria of the skin, facial flushing and sweating, palpitations, hot flushes of the body, headache, nausea, vomiting and dizziness. The fish implicated in one outbreak was noted to have a peppery taste. The diagnosis of scombroid poisoning was confirmed by the presence of the clinical syndrome, and by demonstration of high histamine levels in the cooked fish. INTERVENTION AND OUTCOME: Two patients had minor symptoms which had resolved before seeking medical advice. Another two patients had mild symptoms which disappeared after two hours of observation and required no specific treatment. Three patients had evidence of major toxicity which was successfully treated with parenterally administered promethazine. One of the three patients with major toxicity required overnight admission and repeated doses of promethazine to eradicate her symptoms. No patient had symptoms for longer than 12 hours. CONCLUSION: Scombroid poisoning is caused by ingestion of fish which has accumulated scombrotoxin during spoilage. The toxin is heat stable and has been identified as histamine. The clinical presentation closely resembles an acute allergic reaction. This similarity in symptoms may result in the diagnosis of scombroid poisoning being missed by clinicians. Patients with the symptom complex may be incorrectly informed that they are allergic to the fish species. Diagnosis is clinical and can be confirmed by analysis of the histamine content of the fish. Treatment is with antihistamines, however major toxicity may require the same aggressive management as acute anaphylaxis. PMID- 1453999 TI - Crocodile attacks in the Northern Territory of Australia. AB - OBJECTIVE: To examine crocodile attacks in the Northern Territory with particular reference to risk factors, range of injuries, microorganisms isolated from wounds, and surgical management; and to make recommendations for optimal treatment. DESIGN AND SETTING: The case notes of patients treated at the Royal Darwin Hospital within the last decade were reviewed retrospectively. Autopsy and newspaper reports for the same period were also reviewed. RESULTS: There were 16 reported crocodile attacks in Northern Territory waters from June 1981 to June 1991. Four of these were fatal. Most attacks resulted from swimming or wading in shallow water (13/16). Half the victims were known to be affected by alcohol. The majority of attacks occurred in failing light or at night (10/16). Injuries in survivors ranged from minor lacerations and puncture wounds to major abdominal, chest and limb trauma. Death in fatal attacks was caused by transection of the torso or decapitation. Microorganisms isolated from wound swabs included Pseudomonas, Enterococcus, Aeromonas and Clostridium species. CONCLUSIONS: Most attacks in this series could have been prevented by taking adequate precautions. The treatment of crocodile injuries must include (i) adequate wound cultures, (ii) antitetanus prophylaxis, (iii) meticulous wound debridement, (iv) appropriate broad spectrum prophylactic antibiotics and (v) allowing healing by secondary intention or delayed primary closure where appropriate. PMID- 1454000 TI - The role of foxes Vulpes vulpes in the epidemiology of Echinococcus granulosus in urban environments. AB - OBJECTIVE: To survey the prevalence of intestinal worms, particularly Echinococcus granulosus, in foxes in Canberra. DESIGN: The locations of foxes seen in Canberra during this study were recorded. Foxes and macropod marsupials killed on the roads of Canberra were collected and examined for the presence of intestinal helminths and hydatid cysts respectively. METHOD: The intestinal contents of the foxes were washed through a fine sieve and examined microscopically. All helminths recovered were collected and identified. All the internal organs of the macropods were examined for any cystic lesions. RESULTS: Forty-five foxes and 44 macropods were examined. Echinococcus granulosus was found in three of the foxes (7%). Hydatid cysts were not found in the internal organs of any of the macropods examined. CONCLUSIONS: Echinococcus granulosus is present in the urban fox population of Canberra. This hitherto unreported aspect of the epidemiology of E. granulosus in Australia could be a potential public health risk to urban populations. PMID- 1454001 TI - Ocular injuries caused by magpies. AB - This paper presents a series of six patients with ocular injuries resulting from magpie attacks. Five cases involved children. In two cases the penetration was overlooked initially. In one case the keratitis was caused by Bacillus cereus. Full ophthalmic examination, including indirect ophthalmoscopy and microbiological studies, must be undertaken initially to identify unrecognised eye injuries and to prevent the possible sight-threatening complications of vitreal fibrosis with subsequent retinal detachment or endophthalmitis. PMID- 1454002 TI - An oral history of changes in the Australian diet. PMID- 1454003 TI - Electrocution in Western Australia, 1976-1990. AB - OBJECTIVE: To describe the epidemiology of electrical fatalities in Western Australia between 1976 and 1990. DATA SOURCES: Data for the study were gathered from hospital records, autopsy reports and findings from State Energy Commission and coronal investigations. DATA EXTRACTION: Information that was abstracted included age, sex, occupation, voltage, history of incident and autopsy findings. DATA SYNTHESIS: There were 104 victims. Death occurred most frequently in young men exposed to low voltage current during summer, and nearly half the fatalities occurred in the workplace. Water was present in up to 52% of fatalities. Without exception, all victims developed a lethal arrhythmia at the time of exposure to the electric shock, which usually resulted in death at the scene. CONCLUSION: When a victim is exposed to a fatal electric shock, the lethal arrhythmia occurs at the time of electrocution and is just as likely to occur at home as in the workplace. Electrical fatalities can be prevented largely by the use of residual current devices. PMID- 1454004 TI - What doctors need to know. A note on professional performance. PMID- 1454005 TI - Medical litigation. The aetiological role of psychological and interpersonal factors. AB - The present paper focuses upon psychological factors which may cause patients to make formal complaint or embark upon legal proceedings against a doctor despite competent medical management. Although the principles involved arose from experience of liaison psychiatry in neonatal and obstetric settings, they are more broadly applicable to other areas of medical practice. The corner stone of prevention is appropriate psychological management. One of the most common forms of psychological mismanagement is a failure to share information openly with patients when it becomes available. Sometimes, despite exemplary medical and psychological management, grievance proceedings are still initiated. Often in such cases the cause lies in the patient's psychopathology. Finally, formal complaint or litigation may arise as a result of the patient's unrealistic expectations of the doctor. PMID- 1454007 TI - Merry Christmas, Major Clarke! Changi Christmas 50 years ago. PMID- 1454006 TI - Dr John Thomson (1847-1909). Pioneer surgeon, military surgeon and a founder of St John Ambulance in Australia. AB - Surgeon John Thomson (1847-1909), a Scot who made his life's work in Queensland, was a pioneer surgeon, radiologist and bacteriologist, and one of the founders of the St John Ambulance movement in Australia and the Railway Ambulance Corps. He was variously President of the British Medical Association (Queensland Branch), the Medical Board of Queensland, the Medico-Ethical Association, and the Intercolonial Medical Congress, which was held in Brisbane in 1899. A pioneer military surgeon in this country, he was the foundation Principal Medical Officer (as Surgeon-Major) of the Queensland Ambulance Corps within the Queensland Defence Force. His advocacy for a university north of Sydney was one of the factors which led to the foundation of the University of Queensland, a body which honoured him by the establishment of the John Thomson Lectureship, which for half a century was its most prestigious public oration. The life and times of this singular doctor exemplify one small class of pre-Federation medical pioneers whose professional outreach established a number of voluntary organisations which have blossomed in Australian society to the present day. PMID- 1454008 TI - The first anaesthetics in Australia: an historical update. PMID- 1454010 TI - Doctors and plain English. PMID- 1454009 TI - Appendicitis: historical milestones and current challenges. PMID- 1454011 TI - Other people's practices. Saudi Arabia. PMID- 1454012 TI - Beyond the Barcoo--probable human tropical cyanobacterial poisoning in outback Australia. AB - AIM: To determine the cause of a disease known variously as "Barcoo fever, Barcoo spews, Barcoo sickness", or simply "the Barcoo", once prevalent in outback northern and central Australia. METHOD: Comparison of the recorded symptoms with those of known infectious diseases and gastrointestinal illness; consideration of the epidemiology, including times and places of occurrence and the population affected. RESULT: The disease had features of a toxic rather than an infectious illness and had the characteristics of poisoning by toxic cyanobacteria (blue green algae). In particular the symptoms were similar to those shown to be due to the hepatotoxin of the tropical cyanobacterium Cylindrospermopsis raciborskii (Woloszynska). CONCLUSION: Poisoning by cyanobacterial toxins was once widespread in outback northern Australia and toxic cyanobacteria must still be present in many areas. Although not reported and probably not diagnosed as such, the disease still occurs in mild form. Widespread illness does not occur but individuals still experience symptoms similar to those described a century ago. Precautions are necessary to prevent algal contamination or proliferation in domestic or communal water supplies. PMID- 1454013 TI - Disease-modifying antirheumatic drugs. PMID- 1454014 TI - Prophylaxis against NSAID-induced ulcers. PMID- 1454015 TI - The potential for teratogenicity of vitamin A and its congeners. AB - OBJECTIVE: To review the evidence for teratogenic potential associated with the use of vitamin A and synthetic retinoids in Australia. DATA SOURCES: Relevant indexed journal articles and standard drug information reference texts were identified by Medicine and library search. Information was also obtained from the Australian National Perinatal Statistics Unit. DATA EXTRACTION: We summarised human and animal data relating to the teratogenicity of vitamin A derivatives and synthetic retinoids, including case reports documenting systemic effects from topically administered drugs, pertinent information relating to the clinical pharmacokinetics and adverse effects of these compounds, and the approved and potential indications for the use of these agents. DATA SYNTHESIS: Extensive experimental evidence points to the teratogenicity of natural and synthetic retinoids in animals. Data confirming an effect in humans are not as good. Nevertheless case series, case reports and some epidemiological data regarding isotretinoin suggest that synthetic retinoids are similarly teratogenic in humans. Although there are extensive guidelines and legislation dealing with the use of these compounds in the United States and Australia, the potential for teratogenicity induced by vitamin A still exists. This is because retinoids and vitamin A continue to be prescribed for women of child-bearing potential and documented evidence from the United States reveals that not all prescribers comply with recommendations that minimise the risk of malformations. Non prescription forms of vitamin A are available without a pregnancy hazard warning, and potentially teratogenic amounts are available from dietary sources. CONCLUSIONS: There exists a potential for teratogenicity in association with the use of both synthetic and natural retinoids in Australia. Monitoring systems currently in place in this country may not detect these malformations should they occur. PMID- 1454017 TI - Microbes: the small achievers. PMID- 1454016 TI - Non-steroidal anti-inflammatory drug induced upper gastrointestinal haemorrhage and bleeding. PMID- 1454018 TI - Munchausen syndrome by proxy--a cause of preterm delivery. AB - OBJECTIVE: To present the first case of Munchausen syndrome by proxy involving self-induced preterm delivery. CLINICAL FEATURES: A 27-year-old Caucasian woman induced antepartum haemorrhage and rupture of membranes with a knitting needle at 26 weeks' gestation, leading to delivery of the infant. This "prenatal child abuse" led to a prolonged intensive care stay, extensive treatment and subsequent bronchopulmonary dysplasia. As the child recovered from the effects of extreme prematurity, he became a victim of fabricated illness and recurrent smothering episodes. INTERVENTION AND OUTCOME: After the diagnosis of Munchausen syndrome by proxy was made, the child was removed from the mother and he has since enjoyed good health. CONCLUSION: Self-induction of antepartum haemorrhage can lead to preterm delivery and may be recognisable by certain clinical parameters. The victim of self-induced preterm delivery, if survival ensues, may be subject to further abuse. PMID- 1454019 TI - Open air rock concert: an organised disaster. AB - OBJECTIVE: To describe the planning and implementation of health care provision at a mass gathering, and to describe the conditions treated at such an event. SETTING: When approximately 93,000 fans gathered outdoors in Sydney's Centennial Park, a natural reserve, for Australasia's largest ever outdoor rock concert, there was an obvious potential for medical disaster. PATIENTS: At most disasters or mass gatherings, accurate patient numbers and details are not available, but an organised patient data collection system allowed the case load at this event to be clearly defined. This showed that 450 patients were attended to by the first aid teams. Triage identified 36 of these as having conditions serious enough to require admission to the medical area. Seven of these patients were ultimately transferred to hospital. RESULTS: A brief practical outline is provided of the medical planning for the concert, detailing the staff and equipment, how to avoid potential problems, the use of voluntary organisations, and specific site organisation. Key points in the medical planning, organisation and practicalities, especially those which are vital to any disaster response, are highlighted. CONCLUSION: Solutions to recurrent problems experienced by medical personnel involved with mass gatherings or disasters are suggested. The lack of practice in implementing a multiple casualty or disaster plan may be remedied by organised responses to mass events. PMID- 1454020 TI - Telephone-related lightning injury. AB - OBJECTIVE: To review reported telephone-related lightning injuries, outline the mechanisms of injury and suggest treatment strategies. DATA SOURCES: Cases notified to Telecom Australia and an extensive search of the literature. DATA SYNTHESIS: There is a dearth of literature on telephone-related lightning injury. Some reports note it in passing, others describe single incidents. Case reports from Australia provide detail sufficient for review, and the general principles which govern management of such injuries are presented. CONCLUSION: Telephone related lightning injury is not rare. Practitioners should be aware of the uniqueness of lightning injury and the complexity of its assessment. A research program aimed at further elucidation of the detail of this injury is proceeding. PMID- 1454021 TI - Forensic pathology in Papua New Guinea 1962-1989. PMID- 1454023 TI - Santa psychosis? PMID- 1454022 TI - Platypus envenomation--a painful learning experience. AB - OBJECTIVE: To describe in detail for the first time, the clinical course and medical management of a significant human envenomation by the Australian platypus (Ornithorhynchus anatinus). CLINICAL FEATURES: A 57-year-old man was envenomated via two spur wounds to the right hand from each hind leg of a male platypus. Pain was immediate, sustained, and devastating; traditional first aid analgesic methods were ineffective. INTERVENTION AND OUTCOME: On admission to hospital, narcotics administered intravenously, both intermittently and by infusion, provided inadequate analgesia. A right wrist block was dramatically effective. After the blockade narcotic analgesic support was required for several days. The patient spent six days in hospital, and the envenomated area remained painful, swollen and with little movement for three weeks. Significant functional impairment of the hand persisted for three months, the cause of which is uncertain. CONCLUSIONS: Male platypus venom remains largely unstudied. It produces savage local pain and marked local swelling, but no apparent tissue ischaemia. No antivenom is available; in its absence the only effective analgesia appears to be regional nerve blockade, when the envenomation site and available skills permit. Immobilisation assists. PMID- 1454024 TI - There's a worm in my eye. AB - OBJECTIVE: To report a case of an unusual worm infestation of the eye. CLINICAL FEATURES: A 28-year-old veterinary surgeon complained of the intermittent appearance of a worm in her eyes. Her previous camping travels in west and central Africa suggested the diagnosis of Loa loa, which was confirmed on surgical removal of the worm from beneath the conjunctiva. Laboratory investigations showed peripheral blood eosinophilia, negative thick blood film examinations for microfilariae and positive results of filarial serology. INTERVENTION AND OUTCOME: The worm was removed intact after incision of the overlying conjunctiva. Diethylcarbamazine was prescribed and the patient remained asymptomatic in the subsequent 12 months. CONCLUSIONS: The sighting of a worm in the eye is rare in Australia and usually occurs in immigrants or returned travellers. Loa loa is the most common offending species and is identifiable and treatable. PMID- 1454025 TI - Lead poisoning from Indian herbal medicine (Ayurveda) AB - OBJECTIVE: To present a case of lead poisoning following ingestion of Indian herbal medicine. CLINICAL FEATURES: A 37-year-old man presented with a history of abdominal pain, anorexia and malaise. He had recently returned from a trip to India where he had been taking two different herbal tonics. Investigation revealed low-grade hepatitis and normocytic anaemia with prominent basophilic stippling. The blood lead concentration was high, and analysis of the herbal tablets revealed a very high lead content. INTERVENTION AND OUTCOME: The patient required narcotic analgesia for abdominal pain and was treated with chelation therapy with calcium ethylenediaminetetra-acetate (calcium EDTA) for five days which resulted in a high urinary excretion of lead and resolution of his symptoms over a period of several days. CONCLUSION: Lead poisoning in Australia is usually the result of chronic industrial exposure, but practitioners should be aware of the possibility of poisoning from other domestic sources such as unglazed pottery, cosmetics and herbal remedies, especially those from Asia and India, in which lead may be present in high concentration. Patients from Asia who present with unexplained anaemia or abdominal symptoms should be asked about exposure to such sources. PMID- 1454026 TI - Oestrogen and breast cancer. PMID- 1454027 TI - Report on the effects of introducing primidone for essential tremor. PMID- 1454028 TI - Preventing obesity. PMID- 1454029 TI - Complication of cryotherapy. PMID- 1454030 TI - Gastrointestinal endoscopy. PMID- 1454031 TI - HIV antibody testing of pregnant women. PMID- 1454032 TI - Retropubic extraperitoneal endoscopy. PMID- 1454033 TI - The management of terminally ill patients. PMID- 1454034 TI - AIDS--beyond education. PMID- 1454035 TI - AIDS--beyond education. PMID- 1454036 TI - Indoor air quality and sick buildings. PMID- 1454037 TI - Peak flow errors. PMID- 1454038 TI - A follow-up study of attentional behavior in 6-year-old children exposed prenatally to marihuana, cigarettes, and alcohol. AB - Attentional behavior was examined in one hundred twenty-six 72-month-old children for whom prenatal exposure to marihuana, cigarettes, and alcohol has previously been ascertained. Discriminant Function Analysis revealed a dose-response association between prenatal cigarette exposure and impulsive behavior as manifest on poorer performance on a response inhibition task and increased errors of commission on a sustained vigilance task. Performance on a series of memory tasks particularly those requiring verbal recall was also negatively associated with maternal cigarette use. Prenatal marihuana habits were associated with increased omission errors in the vigilance task, possibly reflecting a deficit in sustained attention. In addition, Discriminant Function Analysis revealed a dose response relationship between prenatal marihuana use and a higher rating by the mothers on an impulsive/hyperactive scale. Relatively low levels of maternal alcohol consumption was related to decreased impulsive responding both in the response inhibition task and in terms of the mothers' perception of the child's behavior. The multifaceted approach of examining attentional behavior was essential to reveal the differential associations with the three prenatally used drugs. The implications of the observations and how the findings relate to and extend the existing literature is discussed. PMID- 1454039 TI - Prenatal cocaine exposure in the laboratory mouse: effects on maternal water consumption and offspring outcome. AB - Pregnant mice were given 50 mg/kg cocaine HCl (1% solution, sc) once daily from gestation days 7 through 18 (sperm positive = day 0; term = day 19). Pair-fed and untreated control groups were also used. The pregnant cocaine-treated females showed normal weight gain and food consumption but had significantly increased water consumption. The cocaine-treated group had a significant increase in embryonic resorptions but no significant effects on stillbirths or postnatal mortality. The offspring of cocaine-treated females had significantly reduced birth weights and postnatal weight gains up to the age of 28 days. There was also a delay in their ear opening but not in other maturational milestones. Increased water consumption following cocaine treatment has been reported by other studies. We speculate that cocaine has a diuretic effect. We discuss the implications of this effect during pregnancy. PMID- 1454040 TI - Sociodemographic factors modifying the effect of environmental lead on neuropsychological development in early childhood. AB - A long-term prospective cohort study was conducted to examine the association between prenatal and postnatal exposure to environmental lead and childhood neuropsychological development. The possible interactive effects of blood lead and some covariates on early development were explored in this study. Our data suggest that gender of the child modifies the effect of lead on the neuropsychological development during early childhood. At the ages of 2 and 4 years, girls appear to be more sensitive than boys to the neuropsychological effects of lead. However, there is no significant modification of the effect of lead by some other covariates, such as parental smoking, socioeconomic status, home environment, birth weight, and the kind of infant feeding. Evidence of interactions between environmental lead exposure and other covariates in the causation of neuropsychological deficits in childhood underscores the desirability of considering both main effects and interactions in this area of research. Such effects, if confirmed, may have implications for public health intervention strategies. PMID- 1454041 TI - The effects of prenatal exposure to phenytoin and other anticonvulsants on intellectual function at 4 to 8 years of age. AB - Twenty phenytoin exposed children between 48 and 99 months of age had an evaluation of behavior and intelligence by a single examiner who was unaware of exposure status. The controls were 98 children identified at birth as having three or more minor anomalies. None of the children evaluated were mentally retarded. In both, a case-by-case comparison and a comparison of the two entire groups, the phenytoin-exposed children had significantly lower scores for both Performance IQ (PIQ), Full Scale IQ (FSIQ), and Visual Motor Integration Test (VMIT). Similar abnormalities have been found in studies of animals exposed to phenytoin in utero. These results suggest that the teratogenic effects of phenytoin may include an effect on cognitive function. PMID- 1454042 TI - Prenatal exposure to cocaine. I: Effects on gestation, development, and activity in Sprague-Dawley rats. AB - Sperm-positive Sprague-Dawley rats received one of four treatments for 20 days beginning within 24 hours of conception. One group received subcutaneous injections of 15 mg/kg cocaine twice daily (Cocaine-D); a second group received 15 mg/kg cocaine twice daily for two consecutive days at 5-day intervals (Cocaine I); a third group received normal saline twice daily (Saline); and a fourth group received 1.5 mg/kg amfonelic acid (AFA), a dopamine reuptake inhibitor, once daily. Cocaine-D, Cocaine-I, and AFA dams were fed ad lib. An attempt was made to pair-feed the Saline dams with the Cocaine-D dams; however, the Saline dams did not eat as much as the Cocaine-D dams which resulted in dams in all groups essentially eating ad lib. The Cocaine-D pups showed a slightly delayed righting behavior and neophobia at 30 days of age, as evidenced by hypoactivity during the first 15 min of a 6-h activity test. The Cocaine-I pups were hypoactive during the 3-h dark phase of the 6-h activity test when tested at 30 days of age. These effects did not occur in the offspring exposed to AFA, a potent dopamine uptake inhibitor and CNS stimulant which indicate that one or more other sites for cocaine action may combine for its effects on the developing fetus. PMID- 1454043 TI - Prenatal exposure to cocaine. II: Effects on open-field activity and cognitive behavior in Sprague-Dawley rats. AB - Pregnant rats received subcutaneous injections of 15 mg/kg of cocaine twice daily (Cocaine-D), twice daily for two consecutive days at 5-day intervals (Cocaine-I), 0.9% saline (Saline) twice daily, or 1.5 mg/kg amfonelic acid (AFA) daily from gestational days 1-20. Offspring were tested for: rates of spontaneous alteration at postnatal days (PND) 32, 35, 40, and 45; acquisition and retention performance on a water maze task beginning at PND 30 and 60; entrance into and activity in an open-field apparatus at PND 60 and 180. The Cocaine-D offspring were less likely than Control offspring to enter the open field when tested at PND 60. The Cocaine I offspring were hyperactive in the open-field apparatus when tested at PND 60. The drug treated offspring did not differ from the Saline control animals on all other measures. The failure of the Cocaine-D animals to enter the open field is consistent with neophobic behavior that we have observed before in rats exposed in utero to cocaine. PMID- 1454044 TI - Comparison of two weeks versus one week of prenatal ethanol exposure in the rat on gonadal organ weights, sperm count, and onset of puberty. AB - Sprague-Dawley dams from Harlan Ind. (Indianapolis, IN) were administered a fortified ethanol liquid diet containing 35% ethanol derived calories for two weeks (E-2) beginning on day 7 or one week (E-1) beginning on day 13 of gestation and continuing through parturition. Control dams were pair-fed an isocaloric liquid diet containing no ethanol during these periods or remained on lab chow and water. E-2 dams consumed an average of 13.52 g ethanol/kg bwt during the first week of exposure (days 8-14) and 12.50 g ethanol/kg bwt the second week (days 14-20). E-1 dams consumed significantly less than E-2 dams during the second week (9.75 g/kg; p < 0.0001). Although the lower consumption in E-1 dams led to a significant decrease in maternal weight gained during the few days of pregnancy compared to E-2 dams, birthweights of E-1 offspring were significantly heavier than those of E-2 offspring (p < 0.05). No effect of ethanol was detected on anogenital distance at birth in either sex. Puberty was delayed in female offspring of both E-1 and E-2 dams (p < 0.01) as measured by age of vaginal opening. These data suggest that the primary teratogenic actions of ethanol in the rat on fetal growth, as well as delayed puberty in females, occur in the last week of gestation. In adult E-2 males, testis weight was significantly heavier than all other groups when indexed to body weight. No effect of prenatal ethanol exposure was observed on the indexed weights of prostate, epididymis, or seminal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454045 TI - Prenatal cocaine and alcohol exposures affect rat behavior in a stress test (the Porsolt swim test). AB - Prenatal cocaine and alcohol exposures have been associated with a variety of adverse effects ranging from subtle neurobehavioral abnormalities to major malformations. In this study, we used the Porsolt swim test to assess the effects of prenatal cocaine and alcohol exposures on stress-related behavior. Pregnant Long-Evans rats were injected daily with 80 mg/kg cocaine HCl (SC) or 6.2-6.5 g/kg ethyl alcohol (PO) from gestation days 7-20 with half the dose given in the morning and the other half in the afternoon. Pair-fed and ad lib control groups were also used. One male offspring from each litter was evaluated in the Porsolt swim test at the age of 120 days. The alcohol and cocaine groups were less immobile (i.e., struggled more to escape) than the controls. These results suggest that prenatal exposure to either alcohol or cocaine can adversely affect behavior in stressful or fearful situations. PMID- 1454046 TI - Prenatal ethanol effects on reward efficacy for adult mice are gestation stage specific. AB - We previously reported that adult mice exposed to ethanol throughout gestation (G5-17) responded slower than controls on reinforcement schedules which required large numbers of responses per unit of food, i.e., high fixed ratio (FR) schedules. The primary finding of the present study was that ethanol exposure during the last 5 days of gestation (G12-17) is sufficient to produce this effect whereas a similar exposure early in gestation (G5-10) is not. Both male and female mice exposed to ethanol late in gestation responded slower than either lab chow or pair-fed controls, and the effect was similar to that of mice exposed to ethanol throughout gestation (G5-17) in our earlier study. Thus, developmental events occurring late in gestation are important for the reduced reinforcing efficacy of food for prenatal-ethanol-exposed mice. In addition, the present experiment established the comparability of the sucrose and lab chow controls on this task. The results of the present study and our previous report are compatible with the hypothesis that the reduced responding on high FR schedules exhibited by prenatal-ethanol-exposed mice reflects a reduction in the efficacy of food reward. It is possible that the reduction in reward efficacy is due to altered development of neuronal systems functionally related to reward which develop late in gestation. PMID- 1454047 TI - Individual psychotherapy with psychotic patients: psychotherapeutic issues in prescribing medication. PMID- 1454048 TI - Combining individual and family treatment: guidelines for the therapist. AB - Successfully combining individual and family treatment for psychosis-prone outpatients who live with their families is a process of keeping the needs of the patient and the family in balance. The therapist has to respond to each in an even-handed way that preserves an alliance with both. Through guidelines and case reports, this chapter describes how to maintain that balance. The therapist patient relationship is the core of treatment and keeps the clinician's focus squarely on the individual needs of the patient. In keeping with that focus, the therapist encourages self-determination on the patient's part and sets up opportunities for the family to communicate directly with the therapist in front of the patient, rather than surreptitiously behind the patient's back. In keeping with a collateral emphasis on the family, the therapist involves the family regularly and early in the course of treatment, respects the family's knowledge of the patient, puts that knowledge to use, and works with the family to deal promptly and effectively with incipient emergencies. The therapist knows that it is not only the therapist but also the family who stimulate a patient to change. The therapist, building on whatever strengths the patient and family possess, enlists the family as an ally in promoting and bringing about therapeutic progress. PMID- 1454049 TI - Pre-alliance group: a new strategy for working with treatment-resistant schizophrenics. PMID- 1454050 TI - A current approach to the psychodynamic psychotherapy of substance-dependent individuals. PMID- 1454051 TI - Infertility: psychotherapeutic issues. AB - In supportive therapy with infertility patients, the clinician tries to relieve dysphoria and enhance self-esteem. Dynamically informed supportive interventions are designed to decrease guilt that may relate to past sexual activities, sexually related diseases, or abortions. These interventions should also be empathetic, promote optimism and reality testing, help with problem solving, allow catharsis and ventilation, decrease feelings of isolation and loneliness, educate and clarify, and praise and encourage where appropriate. Mental health clinicians have an important role to play in the treatment of these patients, provided they learn enough about the psychology of the experience of infertility and about the technology utilized in its treatment. As the number of people seeking treatment for infertility grows, the need for skilled therapists for this population will grow at a parallel rate. PMID- 1454052 TI - The meaning of ethnocultural difference: its impact on and use in the psychotherapeutic process. PMID- 1454053 TI - Anxiety disorders: structured psychotherapy. PMID- 1454054 TI - RNA editing in trypanosomes. The us(e) of guide RNAs. AB - Guide RNAs are encoded in maxicircle and minicircle DNA of trypanosome mitochondria. They play a pivotal role in RNA editing, a process during which the nucleotide sequence of mitochondrial RNAs is altered by U-insertion and deletion. Guide RNAs vary in length from 35 to 78 nucleotides, which correlates with the variation in length of the three functionally important regions of which they are composed: (i) a 4-14 nucleotide 'anchor' sequence embedded in the 5' region, which is complementary to a target sequence on the pre-edited RNA downstream of an editing domain, (ii) a middle part containing the editing information, which ranges from guiding the insertion of just one U into one site to that of the insertion of 32 Us into 10 sites, and (iii) a 5-24 nucleotide 3' terminal oligo [U] extension. Moreover, a variable uridylation site creates gRNAs containing a varying segment of editing information for the same domain. Comparison of different guide RNAs demonstrates that, besides the U-tail, they have no obvious common primary and secondary sequence motifs, each particular sequence being unique. The occurrence in vivo and the synthesis in vitro of chimeric molecules, in which a guide RNA is covalently linked through its 3' U-tail to an editing site of a pre-edited RNA, suggests that RNA editing occurs by consecutive transesterification reactions and is evidence that the guide RNAs not only provide the genetic information, but also the Us themselves. PMID- 1454055 TI - In vitro reconstitution of U1 and U2 snRNPs from isolated proteins and snRNA. AB - In this paper we describe a method for preparing native, RNA-free, proteins from anti-m3G purified snRNPs (U1, U2, U4/U6 and U5) and the subsequent quantitative reconstitution of U1 and U2 snRNPs from purified proteins and snRNA. Reconstituted U1 and U2 snRNPs contained the full complement of core proteins, B, B', D1, D2, D3, E, F and G. Both the U1 and U2 reconstituted particles were stable in CsCl gradients and had the expected buoyant density of 1.4 g/cm3. Reconstituted RNP particle formation was not competited by a 50 fold molar excess of tRNA, as determined by gel retardation assays. However, U1 and U2 particle formation was reduced in the presence of an excess of cold U1 or U2 snRNA demonstrating a specific RNA-protein interaction. U1 and U2 snRNPs were also efficiently reconstituted in vitro, utilizing proteins prepared from mono Q purified U1 and U2 snRNPs. This suggests that for the assembly of snRNPs in vitro no auxiliary proteins other than bona fide snRNP proteins appear to be required. The potential of this reconstitution technique for investigating snRNP assembly and snRNA-protein interactions is discussed. PMID- 1454056 TI - Identification and typing of members of the protein-tyrosine phosphatase gene family expressed in mouse brain. AB - Protein-tyrosine phosphatases (PTPases) form a novel and important class of cell regulatory proteins. We evaluated the expression of PTPases in mouse brain by polymerase chain amplification of cDNA segments that encode the catalytic domains of these enzymes. Degenerate primer pairs devised on the basis of conserved protein motifs were used to generate a series of distinct PCR-derived clones. In this way, murine homologues of the human PTPases LRP, PTP beta, PTP delta, PTP epsilon and LAR were obtained. Corresponding regions in their catalytic domains were used to reveal the evolutionary relationships between all currently known mammalian PTPase protein family members. Phylogenetic reconstruction displayed considerable differences in mutation rates for closely related PTPases. PMID- 1454057 TI - Effect of delta-lysin on the phase transitions of lipid assemblies. AB - X-ray small-angle diffraction, differential scanning calorimetry (DSC), and temperature scanning densitometry (TSD) were used to study the effect of delta lysin on the phase transitions of lipid assemblies from 1,2-0-dixehadecyl-sn glycero-3-phosphocholine (DHPC). The experiments were carried out in excess of water in a temperature range of 0-55 degrees C, and at low peptide concentrations between 10(-4) and 10(-2) moles peptide per mole phospholipid. The incorporation of delta-lysin into lipid assemblies alters the lipid structure without significant changes on the temperatures of phase transition from gel to liquid crystalline phase. The temperature of the main transition was nearly unaffected. A reduction in the transition volume of the lipids with increasing concentrations of delta-lysin was observed. The minor changes in these parameters were interpreted as long-range structural changes caused by the peptide incorporation. The results are discussed in terms of the concept of cooperative phase transition of entire clusters occurring within a membrane implying that relative stable domains of gel phase, and liquid crystalline phase co-exist. PMID- 1454058 TI - Nucleotide sequence of a pregnancy-specific beta 1 glycoprotein gene family member. Identification of a functional promoter region and several putative regulatory sequences. AB - The pregnancy-specific beta 1 glycoprotein (PSG) genes encode a group of heterogeneous proteins produced in large amounts by the human syncytiotrophoblast. Their expression seems to be regulated at the transcriptional level during normal pregnancy. In the present work, we isolated from a human placental library a 17 kb genomic fragment corresponding to a member of the PSG multigene family. DNA sequence analysis of 1190 nucleotides upstream of the translational start and of the first intron, revealed the presence of several putative regulatory sequences. In a transient chloramphenicol acetyltransferase expression assay, 5' flanking sequences within 123 nucleotides upstream to the first major transcription initiation site, functioned as a strong promoter in COS-7 cells. Meanwhile, sequences 5' further upstream had the ability to abolish this promoter activity. The sequence analyzed did not contain any obvious TATA-like boxes or G+C-rich regions, suggesting the existence of unique promoter elements implicated in transcription initiation and regulation of this PSG gene family member. PMID- 1454059 TI - Autoantibodies to nucleolin cross-react with histone H1 in systemic lupus erythematosus. AB - IgM autoantibodies to nucleolin and histone H1 are strongly associated in the serum of patients with systemic lupus erythematosus. IgM eluted from immobilized nucleolin specifically stained histone H1 blotted to nitrocellulose; conversely, IgM eluates prepared from immobilized histone H1 stained nucleolin blots. We conclude that the linkage of anti-nucleolin and anti-histone H1 autoantibodies in SLE is due, at least in part, to immunologic cross-reactivity between these two autoantigens, which share certain similar structural features. PMID- 1454060 TI - Refined definition of the 56K and other autoantigens in the 50-60 kDa region. AB - Alteration of the acrylamide:bisacrylamide ratio in the SDS-polyacrylamide gel used for Western blotting strongly improved the unambiguous detection of antibodies against 50-60 kDa autoantigens present in autoimmune patient sera. The relative migration of Ro52, the 56K autoantigen and calreticulin increased with reduced acrylamide:bisacrylamide ratios in contrast to that of Ro60, La and Jo-1. These analyses indicated that these six autoantigens correspond to six distinct polypeptides. Further analyses using recombinant calreticulin showed that (i) the 56K autoantigen is neither identical nor related to calreticulin and (ii) calreticulin is not a Ro autoantigen. A series of experiments designed to better characterize the 56K autoantigen showed that (i) the antigen is not detectable in fixed cells, presumably due to masking of the epitopes; (ii) about equal amounts of the antigen were recovered in nuclear and cytoplasmic cell fractions after enucleation of the cells; (iii) the 56K autoantigen is not stably associated with either RNA or other proteins. PMID- 1454061 TI - Effect of deletions 5' to the translation initiation sequence on the expression of an mRNA in animal cells. AB - To learn if an mRNA.18S rRNA interaction or a special secondary structure in the mRNA start region is essential for translation in eukaryotic cells, we constructed recombinant plasmids with the SV40 early promoter 5' to part of the Escherichia coli tufB-lacZ gene. Deletion of bases potentially complementary to the 18S rRNA highly increased the transient beta-galactosidase expressed in transfected CHO cells. Deletion of bases that fostered formation of potential hairpins with the mRNA 5'-terminus or altered the structure of the coding region reduced beta-galactosidase activity suggesting that these features of the mRNA secondary structure may be essential for initiation of translation. Computer aided analysis of the potential structure of 290 mRNAs suggests these are conserved features of the initiation region. PMID- 1454062 TI - Engagement of the TcR/CD3 complex stimulates p59fyn(T) activity: detection of associated proteins at 72 and 120-130 kD. AB - Engagement of the T cell antigen-receptor complex (TcR/CD3) induces the rapid tyrosine phosphorylation of a spectrum of substrates whose modification is crucial to the activation process. Although CD4-associated p56lck and TcR/CD3 associated p59fyn(T) could account for this cascade, TcR/CD3 driven stimulation of p59fyn(T) activity has not been demonstrated. In this study, we confirm in Brij 96 based buffers that p59fyn(T) can be co-purified in association with the TcR/CD3 complex, and further demonstrate that antibody-induced cross-linking of TcR/CD3 on the cell surface results in a dramatic increase in the detection of receptor associated kinase activity. This results in an increased phosphorylation and detection of TcR/CD3-p59fyn(T) associated zeta (16-21 kD), p72 (72 kD) and p120/130 (120-130 kD) chains. A distinction between increased recruitment and/or activity of p59fyn(T) was not possible due to the fact that receptor associated p59fyn(T) could not be detected by immunoblotting. However, an alternative approach using membrane vesicles demonstrated an anti-CD3 mediated induced increase (2-5-fold) in the phosphorylation of the fyn kinase. Augmented catalytic activity was accompanied by p59fyn(T) labelling at the autophosphorylation site Tyr420, consistent with stimulated fyn catalytic activity, as well as the phosphorylation of polypeptides at 18-20 (TcR zeta), 31, 90 and 130 kD. Stimulation of fyn activity implicates this kinase as a mediator of the tyrosine phosphorylation events originating from the TcR/CD3 complex. PMID- 1454063 TI - Localization and characterization of the carbohydrate-binding site of the porcine lymphocyte mannan-binding protein. AB - Mannan-binding proteins found in the liver and serum of several vertebrate species are supposed to play an important role in the intracellular transport of glycoproteins, as well as in several protective reactions including complement activation and elimination of various pathogens. To study these protective functions at molecular level it is necessary to understand the fine oligosaccharide specificity and mutual relation among various forms of these soluble lectins. We have isolated mannan-binding protein as peripheral membrane proteins of porcine lymphocytes. This lectin was purified to homogeneity and shown to possess many properties in common with the well studied rat liver proteins (mol. mass, subunit composition and general organization of the molecule). Binding studies performed with three series of defined oligosaccharides (high mannose, hybrid type, and complex) on native lectin molecules as well as isolated carbohydrate-binding domains revealed distinctive features of this mannan-binding protein, including its impaired ability to bind the oligosaccharide ligand after reduction and decyclization at core N-acetyl-D glucosamine 1. PMID- 1454064 TI - Expression of the V(D)J recombinase gene RAG-1 is tightly regulated and involves both transcriptional and post-transcriptional controls. AB - The V(D)J recombinase activating genes, RAG-1 and RAG-2, are coexpressed only in immature lymphocytes, and are sufficient and necessary for V(D)J recombination to occur in non-lymphoid cells. In order to examine control mechanisms operative in the regulation of RAG-1 and RAG-2, we have studied the pattern of expression of these genes in human pre-T cells, pre-B cells, and thymocytes treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA); an agent which mimics some of the lymphocyte maturation changes seen in vivo. The expression of RAG-1 and RAG-2 was tightly controlled in a rapid, yet very complex, manner with both positive and negative control elements operating. Treatment of immature lymphocytes with TPA caused the specific and rapid elimination of steady-state RAG-1 and RAG-2 RNA. Nuclear run-on assays showed that TPA completely repressed the transcription of RAG-1 within 30 min. In addition to repressing the transcription of RAG-1, TPA treatment caused the rapid and specific degradation of RAG-1 transcripts by decreasing the apparent half-life of RAG-1 mRNA more than two-fold. As judged by cycloheximide treatment of cells, the effects of TPA were not dependent on new protein synthesis. A labile transcriptional repressor, separate from the TPA-associated repression of transcription, was also active in cells transcribing RAG-1 and RAG-2 RNA. After depletion of this labile repressor by cycloheximide treatment, steady-state RAG-1 and RAG-2 RNA levels, and their transcription rates, were elevated four- to six-fold; but were still susceptible to elimination by TPA treatment. Treatment of pre-T CEM cells with interleukin-2, or theophylline (an agent that increases intracellular cAMP) resulted in a two fold increase in RAG-1 RNA suggesting that lymphokines, either independently or through second messengers, may modulate RAG-1 and RAG-2 expression. The complex, rapid and precise regulation of RAG-1 and RAG-2 expression is consistent with the view that it is necessary for the cell to tightly regulate V(D)J recombinase levels; lower expression may result in inefficient recombination of Ig/TCR genes, whereas increased expression may lead to recombination errors that are deleterious to the cell. PMID- 1454065 TI - Evidence for immunodominance between closely related epitopes in the selection of T cell repertoire: hierarchy of T cell epitopes in a repeating sequence. AB - In a protein antigen the number of epitopes that are presented by the MHC molecules to the T cells is generally limited. This phenomenon of immunodominance determines the T cell response to a given antigen. To understand the molecular basis of epitope selection we have analysed the hierarchy of T cell epitopes in a repeating synthetic polypeptide antigen Poly 18, Poly EYK(EYA)5 in the mice of H 2d haplotype. Because of its repeating nature, all the potential epitopes of Poly EYK(EYA)5 generated as a result of antigen processing will have extensive sequence overlap, therefore, providing an excellent system to investigate the molecular basis of T cell peptide epitope selection in vivo. We have synthesized a series of 12 and 15 amino acid peptides to mimic these epitopes. In H-2d mice Poly EYK(EYA)5 elicits T cell clones that optimally react with 15 amino acid peptides EYK(EYA)4 and/or (EYA)5. Similar results were obtained when related 12 amino acid peptides EYK(EYA)3 and/or (EYA)4 are used. (EYA)5 reactive T cell clones appear to be very heterogenous and much larger in number than EYK(EYA)4 reactive clones. (EYA)5 reactive clones could be elicited by at least three short Poly-18 derived epitopes (EYA)4, EYK(EYA)3 and (EYA)3EYK while EYK(EYA)4 reactive clones elicited only by the EYK(EYA)3 epitope. However, we observed the dominance of (EYA)5 reactive clones even when EYK(EYA)3 was used as an immunogen and this could be related to the degeneracy of their antigen specificity. Our earlier antigen competition studies suggest that (EYA)5 does not compete with EYK(EYA)4 epitope in binding to I-Ad. Therefore, there is no intramolecular competition between these epitopes to activate T cells. The epitope (EYA)3EYK appears to be subdominant since it can elicit Poly EYK(EYA)5 specific T cells upon immunization but does not appear to be part of Poly EYK(EYA)5 repertoire. Peptides such as (EYA)2EYKEYA or EYAEYK(EYA)2 with lysine substitution in the middle of the sequence were non immunogeneic. Similar results were obtained when the larger 15 amino acid peptides were used as antigen. Another level of epitope immunodominance is seen when substituted peptides of the two immunodominant epitopes are used. Some of these epitopes have potential to be part of the Poly 18 repertoire but they are greatly under represented when intact Poly 18 is used as antigen. The unusual hierarchy observed for immunodominance in these overlapping epitopes of EYK(EYA)5 sequence suggest a bias in the selection of T cell repertoire based upon the crossreactivity between potential epitopes generated as a result of antigen processing. PMID- 1454066 TI - Role of inter-heavy and light chain disulfide bonds in the effector functions of human immunoglobulin IgG1. AB - The role of inter-heavy and light chain disulfide bonds in the effector functions of human IgG1 was investigated. This was accomplished by mutating appropriate sites in IgG1 such that the disulfide bond pattern now resembled that of IgG4. The effector functions of the mutant antibody were then compared to native IgG1 and IgG4. The antibody-dependent cell cytotoxicity activity was completely abolished in the mutant and the complement-dependent cytotoxicity assay was reduced fifteen-fold. The results suggest that the inter-heavy and light chain disulfide bond pattern of an antibody molecule play a role in its effector functions. PMID- 1454067 TI - Molecular analysis of human immunoglobulin V lambda germline genes: subgroups V lambda III and V lambda IV. AB - Three human immunoglobulin V lambda germline genes have been isolated: two from the V lambda IV subgroup and one from the V lambda III subgroup. The V lambda III gene and one of the V lambda IV genes appear to be functional (each being utilized in at least two expressed V lambda genes), despite deviations from the reported consensus sequences in their promoter TATA-box and recombination signal sequence elements. The other V lambda IV gene is a pseudogene. Of the 20 human V lambda germline genes characterized to date, 45% are pseudogenes or vestigial genes. PMID- 1454068 TI - Highlights of controversial issues in anaesthetic reactions. AB - This chapter will first briefly deal with some of the controversial issues surrounding allergic reactions to anaesthetics. Other points which appear to be of fundamental importance and which need further investigation will also be mentioned. Readers are referred to other chapters for further information on some of the issues. PMID- 1454069 TI - Skin tests in diagnosis of allergy to muscle relaxants and other anesthetic drugs. PMID- 1454070 TI - Predictive checkup for risk of anaphylactoid shock in anesthesia. PMID- 1454071 TI - Anaesthetic allergy and prospective radioallergosorbent testing. PMID- 1454072 TI - Anaesthesia-related liver disease. PMID- 1454073 TI - Statistical aspects of preoperative screening for anaesthetic allergies. PMID- 1454074 TI - Allergic reactions to anaesthetics: economic aspects of pre-operative screening. PMID- 1454075 TI - Legal liability for anaphylactic shock. PMID- 1454076 TI - [Plasmids for biodegradation of 2,6-dimethylpyridine, 2,4-dimethylpyridine, and pyridine in strains of Arthrobacter]. AB - Arthrobacter crysallopoietes strain KM-4 degrading 2,6-dimethylpyridine and strain KM-4a degrading both 2,6-dimethylpyridine and pyridine, Arthrobacter sp. KM-4b degrading 2,4-dimethylpyridine were isolated from soil. Arthrobacter crystallopoietes KM-4 and Arthrobacter sp. KM-4b contain 100 Md plasmids pBS320 and pBS323. Arthrobacter crystallopietes KM-4a harbours a 100 Md and 80 Md plasmids. Plasmid curing and conjugation transfer results confirm that these plasmids are involved in degradation of 2,6-dimethylpyridine, 2,4 dimethylpyridine and pyridine. A mutant with lost ability to degrade 2,6 dimethylpyridine was isolated during the growth of strain KM-4 rifR at 42 degrees C. Electrophoretic analysis of the plasmid from temperature sensitive mutant revealed the deletion the size of 26 Md from pBS320 plasmid. PMID- 1454077 TI - [Induction of the SOS-like system in Rec-mutants of Bacillus subtilis]. AB - Influence of the recE1, recB2, recB3, recB19, recF15, recF18, recL16, recM13 and recM27 mutations of the induction of the SOS-like system component, i. e. the RecE protein of Bacillus subtilis was studied by RIA-dot-blot method in UV irradiated or treated by nalidixic acid cells. These agents caused a significant increase in the wild type (rec+) cells but did not stimulate the RecE synthesis in the rec mutants tested. The two exceptions were recB2 and recF18 mutants treated by nalidixic acid. The tsi23 mutation caused thermoinduction of phi 105 bacteriophage in the rec+ genetic background while no prophage particles were induced in the recE, recF, recL, recM mutants. The data suggest that the genetic damage of several rec genes including recB, recE, recF, recL and recM can block induction of the SOS-like system of Bacillus subtilis. PMID- 1454078 TI - [Structure of ends of linear plasmid N15]. AB - The complete structure of the pins on the ends of the linear plasmid N15 (telomers) has been defined for procaryotic organisms for the first time. The ends of the plasmid DNA contain the short nonideal inverted repeats (the size of 28 nucleotide bps) differing in only two nucleotide pairs. PMID- 1454079 TI - [Structure of a region in the genome of bacteriophage N15, necessary for formation of hairpins at ends of the linear plasmid prophage]. AB - A fragment containing telRL site of bacteriophage N15 has been cloned in the vector plasmid pUC19. The nucleotide sequence of a small region from EcoRV-PstI fragment has been defined by Maxam-Gilbert technique. The analysis of the obtained sequence has shown the telRL site to be a nonideal palindrome (the size of 56 nucleotide ops) in which two nucleotide pairs differ in the positions 12 and 14 on both sides of the palindrome centre. The DNA region with alteration of purines and pyrimidines (GC) surrounded by AT-rich regions: 5'-ATTATACGCGCGTATAAT 3'--in the symmetry centre of palindrome is characteristic of the telRL site structure. This characteristic of the region may play a key role in recognition of the site by the specific enzyme at formation of linear prophage-plasmid during lysogenization. PMID- 1454080 TI - [Cloning the asd and lysC genes from Cornyebacterium glutamicum]. AB - Plasmids carrying an asd gene from a mutant. S-(2-aminoaethyl)-L-cysteine resistant strain of Corynebacterium glutamicum were selected from a clonoteque constructed on a plasmid cloning vector pSL5 by complementation of asd mutation in Escherichia coli. Evidence has been obtained that the cloned chromosomal DNA fragment contains also a complete sequence for feed-back-resistant aspartokinase lysC gene. PMID- 1454081 TI - [Analysis of deletions in the dystrophin gene by the multiplex amplification method in patients suffering from Duchenne's muscular dystrophy]. AB - Multiplex polymerase chain reaction was carried out with the material from 68 patients suffering from Duchenne muscular dystrophy in Moscow and Leningrad clinics. Six pairs of oligoprimers were used. Deletions were detected in the material from 22 patients. A new type of deletion was found. Data on deletion frequencies and spectrum were compared with the results published by other authors. PMID- 1454082 TI - [A new R-plasmid from Yersinia pseudotuberculosis]. AB - Yersinia pseudotuberculosis strain 140-P isolated from soil in the Far East was found to harbour an R-plasmid different from the plasmids that had been isolated from the bacteria previously. A new R-plasmid pLD140 is conjugation proficient and codes for the cellular resistance to streptomycin, tetracycline and sulfonamides. The plasid belongs to incompatibility group IncP. Its restriction endonucleases BamHI and SalI profile is different from the ones of the plasmids belonging to the RP4 family. PMID- 1454083 TI - [Plasmids from bacilli related to BAcillus subtilis]. AB - The basic structural and functional properties of natural bacilli plasmids are analyzed in this review. Bacilli plasmids are mostly cryptic, but some are found to have selective markers. Small plasmids replicate by rolling-circle mechanism, however, the replication of large plasmids is likely to occur by the theta mechanism. Plasmid structures involved in replication are analyzed. The bacilli plasmids are stable. They are promising material for vector construction. PMID- 1454084 TI - Discrepancy between self-reported and actual caloric intake and exercise in obese subjects. AB - BACKGROUND AND METHODS: Some obese subjects repeatedly fail to lose weight even though they report restricting their caloric intake to less than 1200 kcal per day. We studied two explanations for this apparent resistance to diet--low total energy expenditure and underreporting of caloric intake--in 224 consecutive obese subjects presenting for treatment. Group 1 consisted of nine women and one man with a history of diet resistance in whom we evaluated total energy expenditure and its main thermogenic components and actual energy intake for 14 days by indirect calorimetry and analysis of body composition. Group 2, subgroups of which served as controls in the various evaluations, consisted of 67 women and 13 men with no history of diet resistance. RESULTS: Total energy expenditure and resting metabolic rate in the subjects with diet resistance (group 1) were within 5 percent of the predicted values for body composition, and there was no significant difference between groups 1 and 2 in the thermic effects of food and exercise. Low energy expenditure was thus excluded as a mechanism of self reported diet resistance. In contrast, the subjects in group 1 underreported their actual food intake by an average (+/- SD) of 47 +/- 16 percent and overreported their physical activity by 51 +/- 75 percent. Although the subjects in group 1 had no distinct psychopathologic characteristics, they perceived a genetic cause for their obesity, used thyroid medication at a high frequency, and described their eating behavior as relatively normal (all P < 0.05 as compared with group 2). CONCLUSIONS: The failure of some obese subjects to lose weight while eating a diet they report as low in calories is due to an energy intake substantially higher than reported and an overestimation of physical activity, not to an abnormality in thermogenesis. PMID- 1454085 TI - Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. AB - BACKGROUND: Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. METHODS: We traced patients with transfusion-related non A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death Index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. RESULTS: Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. CONCLUSIONS: In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease. PMID- 1454086 TI - Sympathetic overactivity in patients with chronic renal failure. AB - BACKGROUND: Hypertension is a frequent complication of chronic renal failure, but its causes are not fully understood. There is indirect evidence that increased activity of the sympathetic nervous system might contribute to hypertension in patients with end-stage renal disease, but sympathetic-nerve discharge has not been measured directly in patients or animals with chronic renal failure. METHODS: We recorded the rate of postganglionic sympathetic-nerve discharge to the blood vessels in skeletal muscle by means of microelectrodes inserted into the peroneal nerve in 18 patients with native kidneys who were undergoing long term treatment with hemodialysis (of whom 14 had hypertension), 5 patients receiving hemodialysis who had undergone bilateral nephrectomy (of whom 1 had hypertension), and 11 normal subjects. RESULTS. The mean (+/- SE) rate of sympathetic-nerve discharge was 2.5 times higher in the patients receiving hemodialysis who had not undergone nephrectomy than in the normal subjects (58 +/ 3 vs. 23 +/- 3 bursts per minute, P < 0.01). In contrast, the rate of sympathetic-nerve discharge was similar in the patients receiving hemodialysis who had undergone bilateral nephrectomy (21 +/- 6 bursts per minute) and the normal subjects. The rate of sympathetic-nerve discharge in the patients receiving hemodialysis who had not undergone nephrectomy was also significantly higher (P < 0.01) than that in the patients with bilateral nephrectomy, and it was accompanied in the former group by higher values for vascular resistance in the calf (45 +/- 4 vs. 22 +/- 4 units, P < 0.05) and mean arterial pressure (106 +/- 4 vs. 76 +/- 14 mm Hg, P < 0.05). The rate of sympathetic-nerve discharge was not correlated with either plasma norepinephrine concentrations or plasma renin activity. CONCLUSIONS: Chronic renal failure may be accompanied by reversible sympathetic activation, which appears to be mediated by an afferent signal arising in the failing kidneys. PMID- 1454087 TI - Brief report: successive occurrence of T-cell and B-cell lymphomas after renal transplantation in a patient with multiple cutaneous squamous-cell carcinomas. PMID- 1454088 TI - Asthma. AB - There is an active inflammatory process in the airways of patients with asthma, even when the patients are asymptomatic. Some of the types of cells involved in this process possess the necessary biologic activities to produce many of the pathophysiologic features of asthma, but the underlying mechanisms have not yet been elucidated. Reducing the severity of the inflammatory process appears to be a reasonable goal of therapy, with potential long-range implications for the morbidity of asthma. Whether this theoretical benefit will be realized awaits further observation. PMID- 1454089 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 52-1992. Progressive pulmonary air-space disease in a 71-year-old man with emphysema. PMID- 1454090 TI - Obesity and efforts to lose weight. PMID- 1454091 TI - Chronic hepatitis C virus infection--a disease in waiting? PMID- 1454092 TI - Prenatal screening for Down's syndrome. PMID- 1454093 TI - Hepatitis B and C infection in an institution for the developmentally handicapped. PMID- 1454094 TI - Metastases and spinal cord compression. PMID- 1454095 TI - Metastases and spinal cord compression. PMID- 1454096 TI - Seizures and treatment for cerebral cysticercosis. PMID- 1454097 TI - Hormone-replacement therapy and pulmonary leiomyomatosis. PMID- 1454098 TI - The American health care system--managed care. PMID- 1454099 TI - AIDS update. PMID- 1454100 TI - Dressing effects on wound healing. PMID- 1454101 TI - Some ethical dilemmas for nurses in clinical practice. PMID- 1454103 TI - The value of a birth plan. PMID- 1454102 TI - Theatre environmental control. PMID- 1454104 TI - Where is the team-work in psychiatric hospitals? PMID- 1454105 TI - Managing change. PMID- 1454106 TI - Nursing education in the USA. PMID- 1454107 TI - Drugs and the gastrointestinal tract. PMID- 1454108 TI - The development of professional nursing education. Part I: Great Britain the Nightingale era (1860-1900). PMID- 1454109 TI - Oncology nursing education in Southern Africa. PMID- 1454110 TI - Diabetic dietary recommendations. PMID- 1454112 TI - CQI (QA 3--the revolution) PMID- 1454111 TI - Physicians--bane or boon for health care delivery? PMID- 1454113 TI - Transient ischemic attack (TIA) secondary to subdural hematoma. AB - Subdural hematomas many sometimes clinically resemble Transient Ischemic Attacks (TIA's). We present three cases which were initially evaluated for, diagnosed as having and were treated for TIA's, but later were found to have subdural hematomas. As in case one, patients with subdurals may have antecedent head trauma which they may or may not recall. Patients presenting with symptoms resembling TIA's need a complete neurologic evaluation. The differential diagnosis for TIA's includes arteriosclerotic extracranial vascular disease, cardiac emboli, migraine, seizure disorder, and mass lesions. Since the prognosis and treatment differs one needs to determine the etiology of the symptoms before treatment is initiated. Specifically, other diagnoses must be excluded prior to anticoagulation therapy, as evidenced by case 2. PMID- 1454114 TI - Resources for medical decision-making in situations of high uncertainty. AB - The high standards of medical practice rest on the assumption that a physician's competence equips him or her to act on a patient's behalf. The conundrum created by medical uncertainty regarding the patient's diagnosis or the appropriate course of treatment seldom receives attention in the medical literature. This article highlights how the age-old medical ideal of beneficence, the modern concept of probabilities, the added dimension of treatment modification based on patients' preferences, and a compassionate disposition operate as competence supporting tools in high uncertainty medical situations. PMID- 1454115 TI - Chickenpox during pregnancy. PMID- 1454116 TI - [Subacute sclerosing panencephalitis (SSPE) in women during pregnancy]. AB - Four women with SSPE during pregnancy were observed. The influence of pregnancy on the course of illness was in all patients unfavourable: the disease exacerbated, what could be explained by physiological immunosuppression connected with gestation. Delivery (in three cases by sectio caesarea) had no beneficial influence on the fatal course of SSPE. In two cases intrauterine necrosis of foetus took place in the 8th and 20th week from the beginning of SSPE. In other two cases healthy children were born. One of them does not exhibit any neurological abnormalities during the first 5 years of life. PMID- 1454117 TI - [IgG1-IgG4 subclasses in the cerebrospinal fluid and blood serum and their synthesis in the central nervous system in multiple sclerosis]. AB - IgG1, IgG2, IgG3 and IgG4 subclasses were detected in cerebrospinal fluid and sera from 32 patients with MS. The CSF levels of IgG1 and IgG3 subclasses in MS patients were significantly higher than those of controls. There were no statistical differences between the values of IgG subclasses in MS and control sera. The IgG1 and IgG3 indices were significantly higher in MS patients than in controls showing that among four IgG subclasses IgG1 ang IgG3 were synthesized in the central nervous system of patients with MS. The elevation of IgG1 and IgG3 indices in MS patients was found more frequently (in about 90% of patients) than the elevation of the general IgG index (in 72% of patients). PMID- 1454118 TI - [Results of prospective 24-hour EEG studies of patients after cranio-cerebral injuries]. AB - In 26 patients 24-hour cassette EEG recording and routine EEG records were taken between 6 and 35 days and again between 6 and 12 months after craniocerebral trauma. Neurological examination and CT of the head demonstrated cerebral concussion in 11 cases and brain contusion in 15 cases. Early after trauma routine EEG was abnormal in 5 cases (19.2%) exclusively in those with brain contusion, and 24-hour EEG recording was abnormal in 16 cases (61.5%), including 7 with cerebral concussion and 9 with brain contusion. In the second half year after trauma 24-hour EEG was normal in 5 cases (19.2%) which had previously abnormal records, and abnormal EEG changes appeared in 6 cases (23.1%) with previously normal findings. Seizure activity was found in the first weeks after trauma in 9 (34.6%) 24-hour recordings. In the second half year after trauma seizure activity was no longer present in 2 cases, but appeared in 6 other cases. Thus 24-hour recording between 6 and 12 months after trauma demonstrated seizure activity in 50% of all patients. In 2 of them epileptic fits developed. The study shows that repeated 24-hour EEG recording after craniocerebral trauma may be important in early detection of patients who are at risk of epilepsy development. PMID- 1454119 TI - [Ischemic stroke in patients under 50 years of age with special reference to its etiology and risk factors]. AB - Eighty-four patients with ischaemic stroke aged 18-50 years were analysed. They had been treated in the years 1985-1989. Forty-five of them were followed up. In a high proportion of cases stroke was a result of thrombosis. Many risk factors were found in this group, mainly hypertension. In most cases stroke was serious, in several cases post-stroke epilepsy and poly-infarction dementia developed. PMID- 1454120 TI - [Neuropathological analysis of 8 cases of clinically diagnosed Reye syndrome]. AB - Authors discuss the possible etiopathogenesis of Reye syndrome (RS) on the base of eight own cases presented in this paper and others previously described. The febrile infection was observed on the beginning of the disease in all actually analysed cases and was followed by symptoms of acute damage of liver and brain. The central nervous system lesions present the changes increasing with time from brain oedema to the necrosis of nerve tissue. The oedematous changes could be recognized as a principal cause of unconsciousness and even of coma in RS. When the etiology of RS remain unknown the clinico-pathological observations of such cases incline to formulate three questions: Is an genetically conditioned background necessary which facilitate toxic or infectious factors to induce the RS? Is the etiology of RS only genetically conditioned? Is an specific viral infection the cause of RS? PMID- 1454121 TI - [Risk factors of leukemic infiltration in patients with acute myeloblastic leukemia]. AB - On the basis of clinical neuropathological evaluation of 48 patients with acute myeloblastic leukaemias the authors analyse the risk factors of leukemic infiltrations developing in the brain. The investigations revealed that the distinct dissemination of leukemic cells in blood is the most important risk factor of such infiltrations. The risk increases significantly in older patients. Survival time and maintenance of high leukocytosis do not intensify the risk of leukemic infiltrations in the brain. PMID- 1454122 TI - [Arteriovenous malformations of the dura mater]. AB - The authors present two cases of dural arteriovenous malformations treated in Dept. of Neurosurgery, Warsaw Medical School. The main clinical problems of this type of AVM are discussed. PMID- 1454123 TI - [Clinical symptoms and the CT image of neoplasm metastases to the brain]. AB - On the basis of 149 CT examinations of cases of brain metastases the neurological symptoms and signs were analysed in relation to the character of the metastasis and the extent of oedema. Stroke beginning of clinical manifestations, loss of consciousness, seizures and neurological syndromes were evaluated. PMID- 1454124 TI - [Neurological sciences and philosophy]. PMID- 1454125 TI - [Use of transcranial Doppler ultrasonography for evaluation of intracranial pressure]. AB - Transcranial Doppler (TCD) studies are very useful for the evaluation of intracranial pressure changes. The most informative for the TCD increase diagnosis are the diastolic pressure decrease and increase of two computed indices: pulsatility index (PI) and resistance index (RI). Single measurements can be misleading and therefore, monitoring of neurosurgical intensive care patients is suggested. Additional information is provided by TCD studies in cerebral blood flow autoregulation tests. The usefulness of TCD in brain death diagnosis is discussed also. PMID- 1454126 TI - [A case of congenital muscular dystrophy with changes in the white matter of the brain]. AB - A case of cerebro-muscular disease is reported in a 5-year-old girl with normal mental development. The changes resembled those in Fukuyama dystrophy, but the clinical picture differs from that dystrophy in normal mental development and absence of other pathological changes in the central nervous system. PMID- 1454127 TI - [Intramedullary metastatic tumor. Case report]. AB - An extremely rare case of intramedullary spinal cord metastasis (Carcinoma solidum metastaticum) is presented. No primary tumour was found. The authors discuss diagnostic and therapeutic problems of treatment in such cases. PMID- 1454128 TI - [Spontaneous cerebrospinal rhinorrhea--report of 2 cases]. AB - The authors present 2 cases of non-traumatic, so called "spontaneous" rhinorrhea. The pathological mechanism of CSF nasal fistula and operation methods are discussed. PMID- 1454129 TI - [A case of superior orbital fissure syndrome]. PMID- 1454130 TI - [Report on the International Quincke Symposium "Barrier concepts and CSF Analysis"; Gottingen, September 18-22, 1991]. PMID- 1454131 TI - [Report on the 7th day of the conference on pediatric neurosurgery Poznan, February 3, 1992]. PMID- 1454132 TI - Astrocyte-endothelial interaction: physiology and pathology. AB - The blood-brain barrier of higher vertebrates is formed by the layer of endothelial cells lining the brain microvessels. The close anatomical association between endothelial cells and perivascular astrocytic end feet suggests cooperation between these cell types in forming and maintaining the blood-brain barrier. This review considers evidence from grafting experiments, developmental studies and culture models of the brain endothelium, concerning the inductive influences acting on the endothelium, and from endothelial cells acting on perivascular astrocytes. Examples from pathology and neurotoxicology which may involve breakdown of induction are also considered. PMID- 1454133 TI - Glioma heterogeneity in vitro: the significance of growth factors and gangliosides. AB - Despite renewed attempts by the WHO at updating the system of classification for brain tumours, most of the dynamic biological processes which underlie both the morphological appearances which form the basis for such systems and the malignant potential of gliomas remain an enigma to the neuropathologist. One feature recognized in human gliomas is their phenotypic and genotypic heterogeneity. Such cellular heterogeneity seen in the histological section is retained in vitro, at least during early passage. It is proposed that this heterogeneity is important in the growth and maintenance of the tumour and may be related to the activity of growth factors and gangliosides. Such molecules may not only influence the histoarchitecture of glial neoplasms but may also determine malignant progression and invasive potential. Moreover, there may be an intimate relationship between growth factors and gangliosides constituting an intricate feedback mechanism upon which the biological progression of gliomas depends. PMID- 1454134 TI - The inflammatory response in the CNS. AB - In recent years it has been recognized that cells of the mononuclear phagocyte lineage, macrophages and microglia, are a major component of gliosis. We review here studies on the kinetics of the myelomonocytic response to acute excitotoxin induced neuronal degeneration and following the injection of endotoxin (LPS) into the parenchyma of the central nervous system. These studies have shown that the kinetics of myelomonocytic recruitment to the parenchyma of the central nervous system is quite unlike that of other tissues; the polymorphonuclear cells are largely excluded and monocytes are only recruited after a delay of several days. The unusual nature of the inflammatory response in the central nervous system needs to be considered when drawing parallels with the acute inflammatory response in other tissues. PMID- 1454135 TI - Transplanted cultured type-1 astrocytes can be used to reconstitute the glia limitans of the CNS: the structure which prevents Schwann cells from myelinating CNS axons. AB - Transplantation of different glial cells into areas of demyelination made in the adult rat spinal cord allows insights into the cell-cell interaction necessary to reconstruct a glial environment around demyelinated axons. Such studies have shown that type-1 astrocytes are central to the exclusion of Schwann cells from areas of glia-free demyelination. However, for these cells to be established in a manner which prevents Schwann cell remyelination of CNS axons, cells of the O-2A lineage are also required. If cultures of isogeneic rat type-1 astrocytes and mouse O-2A cells are transplanted into lesions made in non-immunosuppressed animals. Schwann cell remyelination is limited and extensive oligodendrocyte remyelination is achieved. This paradigm creates a model of immune mediated demyelination in which the immune response is not primarily directed at oligodendrocyte specific epitopes. PMID- 1454136 TI - Genes coding for proteins in central nervous system myelin. AB - There has been considerable interest recently in a genetic component as a causative factor in multiple sclerosis, but the identity of putative susceptibility genes is unknown. In the past decade, the primary amino acid sequences of the four proteins making up 90% of the protein content of central nervous system myelin (proteolipid protein, myelin basic protein, 2',3'-cyclic nucleotide-3'-phosphohydrolase, and myelin-associated glycoprotein) have been determined in several species. Additionally, the structural genes coding for these proteins have been analysed and their human chromosomal localization determined. We have been analysing these genes for possible variants conferring susceptibility to multiple sclerosis. Recent results have shown that cholera and pertussis toxin substrates and low molecular-weight GTP-binding proteins are also present in central nervous system myelin. This implies the presence of signal transducing systems whose purpose is currently obscure. The emerging picture of central nervous system myelin is of a complex dynamic structure composed of many more proteins than was previously thought. PMID- 1454137 TI - Commentary on AIDS and the nervous system. PMID- 1454138 TI - Pathology of the central nervous system in patients infected with the human immunodeficiency virus (HIV): a report of 252 autopsy cases from Brazil. AB - The central nervous system (CNS) was studied in 252 HIV-infected patients from the States of Rio de Janeiro and Sao Paulo in Brazil, the regions with the highest incidence of AIDS in the country. We compared the frequency and morphology of opportunistic infections and CNS changes caused by the HIV, with those described in other series and briefly analysed the risk factors involved in our cases. There were CNS lesions in 230 cases (91.3%), 30 (11.9%) with multiple infections and/or tumours. Most infections were opportunistic (65.4%), including 15.4% viral and 50% bacterial, fungal or protozoal infections. The most frequent was toxoplasmosis (34.1%), followed by cryptococcosis (13.5%), cytomegalovirus (CMV) infection (7.9%) and nodular encephalitis (6.7%). Primary lymphomas were observed in 4% of the cases and HIV encephalitis or leukoencephalopathy in 10.7%. Other opportunistic and HIV associated lesions were present in a limited number of cases and there were also vascular and non-specific lesions. Our study confirms the high frequency of CNS lesions in HIV infected patients. They are morphologically similar to those previously described. However, the higher incidence of toxoplasmosis and cryptococcosis, a lower incidence of viral opportunistic and HIV-associated lesions, and the presence of rarer lesions such as histoplasmosis and chagasic encephalitis, differ from other series, and may reflect geographical and/or socio-economic factors. PMID- 1454139 TI - Morphological spectrum, distribution and clinical correlation of white matter lesions in AIDS brains. AB - This paper analyses the histopathological characteristics and the topographical distribution of 'pure' HIV-associated white matter lesions of the brain in 18 AIDS patients at autopsy; it includes a time-controlled correlation of neuropathology to clinical staging of the AIDS dementia complex. Three distinct lesion types can be delineated: 1 Vacuolar myelin damage (n = 15) in the hemispheric and interhemispheric white matter, in projection fibre tracts, and in intracerebral segments of cranial nerves III, VII, and VIII; 2 Angiocentric foci (n = 14), disseminated randomly in the white matter; 3 HIV leukoencephalopathy (n = 14), as previously defined, seen predominantly in the hemispheric white matter. As a sole lesion type, HIV leukoencephalopathy is found in two cases, while vacuolar myelin damage and angiocentric foci always occur in combination with one or both other types of pathology. Patients with advanced AIDS-dementia complex consistently show severe and combined white matter pathologies at autopsy. We conclude that, in addition to the previously defined features of diffuse HIV leukoencephalopathy, vacuolar myelin damage and angiocentric foci are significant and frequent components of white matter pathology in AIDS autopsies. This reflects the multitude of pathogenetic factors which co-operate in damaging the brain in AIDS. The advanced AIDS dementia complex correlates with the combined and severe white matter lesions. PMID- 1454140 TI - Late effects following central nervous system radiation in a pediatric population. AB - Between 1970 and 1986, 120 children with central nervous system malignancy were treated with radiation therapy. These included 44 low-grade astrocytomas, 11 high grade astrocytomas, 32 medulloblastomas, 15 ependymomas/ependymoblastomas, 3 primitive neuroectodermal tumors and 8 pineal tumors. Seven children were treated without biopsy. Fifty-one treated children were evaluated for the effects of therapy on growth, endocrine function, IQ and hair regrowth. Mean height was 1.5 standard deviations below the mean height for the patient's age at study (range 0 5.7). Height was significantly less in patients receiving radiation to the pituitary and those with somatomedin-C deficiency. Height was also decreased with whole CNS radiation and spine dose > 20 Gy but not to a significant degree. Pituitary radiation in any dose increased the chance of endocrine deficiency (p = 0.004) and 21 of 51 patients had somatomedin-C deficiency. Mean IQ was 92.7 (+/- 18.8), with a slight trend toward decreased IQ with increasing whole brain dose of radiation. Hair regrowth was complete in 20 of 46 evaluated patients, diminished regrowth occurring with increasing volume and dose of radiation. No difference in the measured late effects could be detected with respect to age at treatment, sex, histology or location of tumor. PMID- 1454141 TI - Cerebro-spinal fluid eosinophilia in shunt infections. AB - Hypereosinophilia has been detected in the CSF of 22 patients in a series of 81 cases of shunt infection. It was related with the evolution of the sepsis. Its persistence at the end of treatment appeared to predict later complications, septic or obstructive, and it could be the sign of latent infection. HE might be the result of a specific reaction directed against the infected material, but a non-specific process cannot be eliminated. PMID- 1454142 TI - Cerebral blood flow velocity and failure of autoregulation in neonates: their relation to outcome of birth asphyxia. AB - Using the continuous wave Doppler technique, we examined the pulsatility index (PI) of the anterior cerebral artery in 14 asphyxiated infants. We also measured the blood pressure (BP) and fontanel pressure (FP) and calculated the cerebral perfusion pressure (CPP). According to the neurological prognosis, we divided the 14 infants into two groups and studied correlation of each factor. In the good prognosis group (n = 11), PIs are within normal limits. There is a negative correlation between BP, CPP and PI, suggesting that the autoregulation of cerebral blood flow has been lost. On the other hand, there is no significant correlation between BP, CPP and PI in the poor-prognosis group (n = 3). These infants are thought to have lost the autoregulation, but their cerebral blood flow is not pressure-passive. Not only BP but also brain edema, vasodilation, and possibly other factors may contribute to determine the cerebral blood flow. Concerning FP, no remarkable correlations are found between two groups. It is therefore very important to monitor the PI, BP, FP in asphyxiated infants even if the degree of asphyxia is mild. PMID- 1454143 TI - Transventricular endoscopic investigation and treatment of suprasellar arachnoid cysts. AB - Three children with a suprasellar arachnoid cyst and characteristic neuropathological signs are presented. Through the use of CT scanning and NMR imaging the location, volume and attenuation factors of these cysts can be documented. Stereotactically guided endoscopic exploration of the third ventricle region with visualization and manipulation of the cyst have been performed. This technique should be considered a safe and accurate alternative to craniotomy. PMID- 1454144 TI - Severe type Hunter's syndrome. Polysomnographic and neuropathological study. AB - The clinico-pathological and polysomnographical findings of an adult male patient with severe type of Hunter's syndrome are presented. He died of respiratory failure aged 19, which was much older than the average in this disease. Mucopolysaccharidosis was suspected at the age of one year, and diagnosed by leucocyte enzyme assay at 4 years of age. Mental and physical activity gradually deteriorated until his death. He often showed central type sleep apnea during the sleep stage 2, in addition to common obstructive apnea in Hunter's syndrome. The autopsy showed marked fibrous thickening of the endocardium and valves, enlargement of the liver and spleen, dilatation of the lateral ventricles and diffuse atrophy of the brain. Histologically, diffuse cytoplasmic vacuolations were found in fibroblast-like cells in the thickened endocardium and vascular walls, in Kupffer cells, and in many neurons of the central and peripheral nervous systems. Most neuronal inclusions were considered to be a ganglioside, and in other cells to be a mucopolysaccharide, by their ultrastructure. Massive accumulation of ganglioside in the neurons in the respiratory center might be reflected on central type sleep apnea. PMID- 1454145 TI - Disturbance of GABA metabolism in pyridoxine-dependent seizures. AB - In an infant with typical pyridoxine-dependent seizures, CSF GABA level, was determined before treatment with pyridoxine. Before onset of treatment, level of GABA in CSF was highly lowered (16 pmol/ml), pyridoxine level in serum was within normal range. Immediately after application of 80 mg pyridoxine fits stopped and the EEG was without seizure activity. The data substantiate previous findings in brain tissue from a patient with pyridoxine-dependent seizures. They are proof of a disturbed GABA metabolism in pyridoxine dependent seizures. PMID- 1454146 TI - Congenital caudal spinal atrophy: a case report. AB - An infant presented at birth with symmetrical flaccid paraparesis limited to lower legs and feet, and involving the proximal and distal muscle group. Limitation of the ankle joints was noticed. There were no sensory deficits to painful stimuli and no evidence of loss of sphincter control. Muscle CT revealed severe muscle atrophy in the pelvis and lower limbs, and electromyographic study of the bilateral hamstrings showed polyphasic giant potentials. Motor and sensory nerve conduction velocities were within normal limits, and the spinal MRI showed no structural abnormalities in the cord and the lower spine. These features suggest a congenital segmental abnormality at the anterior horn cell level in the lumbosacral spinal cord, which we propose to call "congenital caudal spinal atrophy". PMID- 1454147 TI - Proton NMR spectroscopy of Canavan's disease. AB - Proton Nuclear Magnetic Resonance (NMR) spectroscopy was used to quantitatively determine cerebral N-Acetyl Aspartate (NAA) concentrations in four patients with Canavan's disease and in four age-matched control subjects. Macroscopic NAA concentrations (mumol/gm wet weight) were not found to be significantly different from controls. Reduced levels of choline and creatine were observed in all patients, and increased levels of lactate and inositol in the eldest three patients. PMID- 1454148 TI - Hereditary progressive dystonia with diurnal fluctuation (Segawa's syndrome)--an unusual case. AB - A young girl with hereditary progressive dystonia with diurnal fluctuation or Segawa's syndrome, completely handicapped and confined to a wheelchair between the age of 5 and 9, revealed an unusually slow response to levodopa. The ability to walk returned only after 12 to 14 months of treatment. Apart from peculiarities of behaviour due to longstanding immobility and ensuing parental overprotection, there were no psychological or mental abnormalities. Other organic diseases were ruled out. A series of regular follow-ups over the course of 7 years was performed. While residual and irregular day-to-day variation of functional capacities almost disappeared after conversion to a preparation with a decarboxylase inhibitor, some mild neurological abnormalities and a slight choreic hyperkinesia persisted with doses providing functional results. The patient today leads an almost normal teenage life and has performed well in school. PMID- 1454149 TI - Severe adverse reaction to carbamazepine: significance of humoral and cellular reactions to the drug. AB - Hypersensitivity to carbamazepine is a well-known phenomenon. The involvement of several organ systems including liver, kidney, bone marrow and other organs have been described. We have observed a 7-year-old boy who had been treated with carbamazepine for seizures. After 10 days of treatment he developed a severe illness with skin rash, high fever, lymphadenopathy, hepatosplenomegaly and lymphopenia. Only slightly decreased complement components and increased complement split products but no circulating immune complexes were demonstrable on admission. Anti-carbamazepine antibodies, T-cell-activation and a significant T-cell reactivity against carbamazepine were found, indicating specific hypersensitivity. Complete recovery was observed after discontinuation of the drug and steroid treatment. PMID- 1454150 TI - Magnetic resonance imaging of progressive hydrosyringomyelia in two patients with meningomyelocele. AB - Two patients who postoperatively developed extensive multiseptated hydrosyringomyelia following surgical repair of a lumbal meningomyelocele are reported. Since MRI has been available, an increasing number of reports showed that MRI is useful in the diagnosis of hydrosyringomyelia. Hydrosyringomyelia can be considered as a dysraphic lesion. Etiology and pathogenesis of hydrosyringomyelia are still not fully understood. Probably arachnoidal adhesions and cord tethering in both patients may be potential factors in producing cystic degeneration of the underlying structure secondary to ischemia. PMID- 1454151 TI - Current bibliographies of neuropeptides prepared by the University of Sheffield Biomedical Information Service. PMID- 1454152 TI - Behavioural effects of two dipeptides L-phenyl alanyl-L-arginine (Phe-L-Arg) and L-phenyl alanyl-D-arginine (Phe-D-Arg) after intracerebroventricular or intrathecal injections in mice. AB - L-phenylalanyl-L-arginine (Phe-L-Arg) and L-phenylalanyl-D-arginine (Phe-D-Arg), dissolved in a physiological saline were injected intrathecally into the lateral brain ventricle, and their behavioural as well as analgesic effects in mice were determined. It was found that a 100 nM dose of either peptide intracerebroventricularly (i.c.v.) injected induced an increase in the locomotor activity and a convulsive effect, whereas the same dose if injected produced a significant analgesic effect. It has been concluded that Phe-L-Arg and Phe-D-Arg have significant but different central effects in mice. PMID- 1454153 TI - Prenatal stress alters the hypothalamic levels of methionine-enkephalin in pup rats. AB - We examined hypothalamic Methionine-enkephalin levels in offspring (postnatal day 10) from stressed female rats in different period of gestation: Group 1, restraint stress day 2 through 6; group 2, restraint stress day 7 through 11; group 3, restraint stress day 12 through day 16 and group 4, restraint stress day 2 through day 16. The hypothalamic levels of Methionine-enkephalin (134.37 +/- 6.19 pg/mg) in the offspring of stressed females from day 2 to day 6 of gestation were significantly (p < 0.001) higher than that obtained in the control group (100.66 +/- 10.13 pg/mg). Similar results were obtained in groups 2 and 3. However, in rat pups from females stressed during 15 days of gestation (group 4) the hypothalamic levels of Methionine-enkephalin (96.5 +/- 6.33 pg/mg) were similar to that obtained in the control group (101.5 +/- 5.15 pg/mg). These results suggest that acute prenatal stress alters the endogenous opioid activity in offspring with possible resultant effects on developmental processes. PMID- 1454154 TI - Structure-activity studies on the effects of atrial natriuretic peptide, brain natriuretic peptide and their analogs on fear-motivated learning behavior in rats. AB - Our previous studies have demonstrated that rat atrial natriuretic peptide (rANP 1-28) and porcine brain natriuretic peptide (pBNP 1-32) administered into the lateral brain facilitate the consolidation of a passive avoidance response and delay the extinction of an active avoidance response in fear-motivated learning in rats. To study the structure-activity relationships in the same learning processes, the effects of several fragments related to ANP and BNP were investigated following their intracerebroventricular administration to rats. The following peptides were studied: rANP 1-28, rANP 5-28, rANP 5-27, rANP 7-23 (ring), rANP 17-23, hANP 10-28, hANP 15-28, hANP 20-28, hANP 1-28, pBNP 1-32 and pBNP 7-32. The peptides were used in equimolar concentration. Two of the peptides studied, ANP 20-28 and ANP 17-23, were ineffective on the extinction of active avoidance behavior and on the consolidation of passive avoidance learning. They exhibited similar actions. The results showed that small fragments of ANP and BNP can carry the biological activity of ANP and BNP on the central nervous system (CNS). It is likely that the biological active center for ANP lies between amino acids 15 and 23 and it is suspected that the ring structure is not absolutely important for the CNS activity. PMID- 1454155 TI - The presence of neuropeptides in GABAergic and cholinergic rat cerebrocortical synaptosome sub-populations. AB - GABAergic and cholinergic synaptosomes from rat cerebral cortex were isolated by a magnetic immunoaffinity technique, i.e. immunomagnetophoresis. These subpopulations were extracted and subjected to radioimmunoassay for four neuropeptides: Neuropeptide Y (NPY); vasoactive intestinal peptide (VIP); substance P (SP); and somatostatin (SRIF). In each of the sub-populations three of the four peptides were enriched in the sorted fraction compared with the mother fraction with respect to the cytosolic marker lactate dehydrogenase (LDH). In the GABAergic sub-population the order was SP > SRIF > NPY > or = VIP whilst in the cholinergic sub-population they were enriched in the order VIP > or = NPY > SP > SRIF. The presence of NPY has not previously been reported in cortical cholinergic neurons. PMID- 1454156 TI - The NMDA-receptor antagonist dizocilpine (MK-801) suppresses the memory facilitatory action of thyrotropin-releasing hormone. AB - Thyrotropin-releasing hormone (TRH) has been shown to improve memory both in animal amnesia models and in humans. In an earlier study we have found that respiratory stimulant action of TRH is mediated through the N-methyl-D-aspartate (NMDA) receptors. Since brain NMDA receptors are implicated in neuronal plasticity, we have investigated whether the non-competitive NMDA antagonist dizocilpine antagonizes the memory-facilitatory action of TRH. TRH (5 mg/kg i.p.) increased passive avoidance scores in the rats in both memory retention and retrieval tests. Dizocilpine (0.2 mg/kg i.p.) caused no significant performance changes. However, it completely blocked the improvement of retention caused by TRH and reversed its effect on retrieval. We conclude that the facilitatory effect of TRH on avoidance retention and retrieval may be mediated by NMDA receptors. PMID- 1454157 TI - Grade II and grade III hypothyroidism in rapid-cycling bipolar patients. AB - Thyroid function was evaluated in 10 rapid-cycling bipolar patients who had previously responded to lithium treatment. Five patients had grade II and 1 patient had grade III hypothyroidism as determined by thyrotropin-releasing hormone tests. Treatment with thyroxine in addition to lithium significantly decreased the intensity and frequency of rapid cycling episodes. PMID- 1454158 TI - Acutely administered haloperidol-induced pattern changes of regional cerebral blood flow in schizophrenics. Observation from subtraction of brain imaging with single photon emission computed tomography using technetium-99m hexamethyl propyleneamine oxime. AB - Changes in regional cerebral blood flow in brain images with single photon emission computed tomography using technetium-99m hexamethyl-propyleneamine oxime before and after intramuscular injection of haloperidol (0.08 mg/kg) were studied in 5 medicated subjects in their twenties, consisting of 5 schizophrenics and 1 patient with histrionic personality disorder, by a subtraction method of brain images. The haloperidol injection induced two types of perfusion pattern change; in 2 of the schizophrenics, a relative hypoperfusion in the frontal lobes in the images prior to injection was converted to a relative hyperperfusion. In the other 3 schizophrenics and in the patient with histrionic personality disorder, the slight left hemispheric dominance was changed to a marked right hemispheric dominance. The results indicate that haloperidol affects perfusion patterns in schizophrenics. PMID- 1454159 TI - Twenty-four-hour beta-endorphin secretory pattern in Alzheimer's disease. AB - A chronobiological study was carried out in 6 male patients (67-71 years), suffering from Alzheimer-type dementia (ATD) and 6 male patients (52-74 years) suffering from multi-infarct dementia (MID), to evaluate their 24-hour beta endorphin and cortisol secretory patterns. Six healthy male adults (28-37 years) and 6 healthy elderly male subjects (78-84 years) constituted the control groups. Blood samples were drawn every 4 h from 8.00 to 20.00 h and every 2 h from 24.00 to 6.00 h. Mean 24-hour beta-endorphin levels were significantly (p < 0.05) higher in the ATD patients (39.2 +/- 1.5 ng/l) than in the other groups (33.8 +/- 1.1, 30.1 +/- 1.6 and 33.2 +/- 1.1 ng/l in the elderly subjects, the adults and the MID patients, respectively). The circadian rhythm was absent in the ATP patients, in the elderly subjects and the MID patients. No differences in plasma cortisol circadian rhythm were observed among the four groups. Our data indicate that changes in circulating beta-endorphin concentrations and circadian pattern may be due to the aging process. PMID- 1454160 TI - Use of buspirone in patients with generalized anxiety disorder and coexisting depressive symptoms. A meta-analysis of eight randomized, controlled studies. AB - This report presents the results of a retrospective analysis of pooled efficacy data from eight studies in which buspirone was compared to placebo in 520 patients with generalized anxiety disorder (GAD). In addition to evaluating overall efficacy in the composite patient data base, four criteria were used to identify subsets of patients with GAD who had coexisting depressive symptoms of at least moderate intensity: (1) a score of > or = 2 on the Hamilton Anxiety (HAM A) Rating Scale item 6 (depressed mood), (2) a score of > or = 2 on the Hamilton Depression (HAM-D) Rating Scale item 1 (depressed mood), (3) a HAM-D total score of > or = 18, or (4) a HAM-D Retardation Factor value (items 1, 7, 8, and 14) greater than the median for the group. Overall, patients treated with buspirone demonstrated significant (p < or = 0.001) improvement over baseline in total HAM A scores compared to patients who received placebo. Buspirone also produced significant (p < or = 0.001) global improvement compared to placebo as assessed by the attending physician. Of the GAD patients stratified according to the four criteria for coexisting depressive symptoms, a substantial percentage (44-64%) of the total patient sample exhibited significant depressive symptoms as part of their anxiety disorder. Patients with GAD and coexisting depressive symptoms of at least moderate intensity exhibited significantly greater improvement with buspirone compared to placebo treatment regardless of the stratification criterion used. They also responded at least as well or better to buspirone therapy as did those with GAD who had less intense depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454161 TI - Tricyclic antidepressant plasma levels after fluoxetine addition. AB - After a review of a pharmacokinetic interaction between tricyclic antidepressants (TCA) and fluoxetine the authors report their own data. They confirm the existence of an interaction of TCA with fluoxetine, in clinical practice, but the fluoxetine was not associated in all cases with a marked increase of TCA plasma levels. The increase appeared especially high with clomipramine (n = 4) and imipramine (n = 3), and lower or dose-dependent with amitriptyline (n = 4). The pharmacokinetic change did not induce side effects in the patients, even when the total TCA plasma level increased to 965 (clomipramine) or 785 (imipramine) ng/ml. The authors then discuss the clinical implication and the possible mechanism of action. PMID- 1454162 TI - Thyroid hormone correlates of sensation seeking and anxiety in healthy human females. AB - The present study explores the relationships among a number of personality measures (the Sensation-Seeking Scale, SSS; the State-Trait Anxiety Inventory, and the Susceptibility to Punishment Scale) and some parameters of the pituitary thyroid axis. The study was carried out on a group of 37 physically and mentally fit female volunteers, none of whom had a personal history of psychiatric or endocrinologic illness. The subjects were controlled for the menstrual cycle. The most relevant result was a significant negative relationship between the SSS score and plasma basal levels of thyroxine (T4) and thyroid-stimulating hormone (TSH). Interaction between T4 and TSH levels with trait anxiety was also observed. PMID- 1454163 TI - Influence of quinidine on the pharmacokinetics of trimipramine and on its effect on the waking EEG of healthy volunteers. A pilot study on two subjects. AB - The pharmacokinetics and pharmacodynamics (waking EEG) of 75 mg trimipramine taken orally were determined in two healthy volunteers on two separate occasions, once without and once after comedication with 2 x 50 mg quinidine. Quinidine, a potent cytochrome P-450IID6 inhibitor, is used as a pharmacological tool to mimic a lack of this enzyme in man. In this study, it markedly altered the pharmacokinetics of trimipramine, almost doubling its plasma half-life and decreasing its apparent clearance and volume of distribution. These results strongly suggest that trimipramine is a substrate of cytochrome P-450IID6. These modifications of trimipramine metabolism were accompanied by measurable changes in some EEG variables, most notably with regard to the relative power in the alpha and theta bands, which showed higher and longer-lasting effects of trimipramine. Since cytochrome P-450IID6 is deficient in 5-10% of Caucasian subjects, this may have consequences in trimipramine-treated subjects, especially with regard to the effects of the drug on the EEG. PMID- 1454165 TI - Regenerating cartilage. PMID- 1454164 TI - Effect of carbamazepine treatment on EEG changes induced by different cortical activation patterns in newly referred epileptic patients. AB - Sixteen epileptic patients suffering from focal epilepsy who underwent antiepileptic drug treatment with carbamazepine (CBZ) for the first time were studied. The EEG was recorded at rest with eyes closed, during blocking reaction (BR), fixation (FIX) and mental arithmetic tasks. The computerized EEG study, performed before and after CBZ therapy, utilized spectral analysis. Data underwent statistical evaluation through Anova and correlation analysis. The parameters evaluated were the mean frequency and the mean absolute and relative power. The results have shown that after CBZ treatment there is a decrease in the alpha reactivity during BR and FIX, while a significant increase in beta activity was observed during all tasks. The effect of CBZ therapy on EEG activity during cortical activation patterns are discussed. PMID- 1454166 TI - Antiperspirants and feet. PMID- 1454167 TI - Cosleeping. PMID- 1454168 TI - Medical planning--Desert Shield/Storm. PMID- 1454169 TI - Where have all the captains gone? A comparison of active and reserve MC ranks and ages, Vietnam to Desert Storm. AB - An analysis of ages and ranks of hospital-based physicians in one area of the Persian Gulf War was used for a comparison with similar data from the Vietnam War. Mean age in the latter was 33.4 years; rank was Captain (0-3.24). In Desert Storm, mean age and rank significantly increased to 46.0 years and close to Lieutenant Colonel (0-4.73), respectively. The large proportion of Reserve Component Physicians (75%) in the Persian Gulf War is the probable explanation for these findings. Medical Corps recruitment and retention problems may result from this most recent war and pose potential threats to success in future U.S. conflicts. PMID- 1454170 TI - Ten leadership steps to a smooth facility upgrade. AB - Leading a medical treatment facility (MTF) through the construction phases of a major upgrade, repair, or any sizable facility project is a challenging and complex endeavor. The Executive Staff can make the process easier on everyone and ensure the final product is in tune with the MTFs needs by taking positive leadership actions. This article describes the effective actions discovered during a 2.5-year-long total MTF upgrade of the 52 Tactical Fighter Wing (TFW) Clinic. These actions involved promulgating a broad systems view of the process, establishing philosophies and criteria, promoting team work, involving customers, and building consensus among the staff. PMID- 1454171 TI - A descriptive analysis of urine cultures: pure versus mixed isolates. AB - Out of 5,670 urine cultures performed in 1989, 1,448 positive cultures with unique results were analyzed. Of these 1,448, 67% were pure cultures, and 50% had at least one isolate with a colony count greater than 100,000 colony forming units/ml. Pseudomonas aeruginosa, Enterococcus faecalis, Proteus mirabilis, Klebsiella pneumoniae, Staphylococcus aureus, and diphtheroids were more likely (p < 0.01) to occur in mixed than pure culture, while Escherichia coli was more likely to occur in pure than mixed culture. The most common organism combinations were diphtheroids-coagulase negative Staphylococcus (30 cultures), E. faecalis coagulase negative Staphylococcus (28), E. faecalis-P. aeruginosa (13), K. pneumoniae-P. aeruginosa (9), and E. coli-P. aeruginosa (9). PMID- 1454172 TI - A descriptive study of mentoring relationships experienced by Army nurses in head nurse or nursing supervisor roles. AB - Mentoring relationships experienced by Army Nurse Corps officers in head nurse or nursing supervisor roles were examined via a survey questionnaire. Findings indicate that career development relationships are occurring among these nurses, but less than half of the relationships consist of mentoring. Nursing supervisors comprised the largest group of career developers, while head nurses were the second most likely group to assist with the development of a novice nurse. Approximately half of the nurses indicated that the career development relationship had a "substantial" influence on their personal lives, and a "very great" influence on their professional lives. PMID- 1454173 TI - The effect of intermediate altitude on the Army Physical Fitness Test. AB - Official physical training records of personnel stationed at intermediate altitude (elevation 5,280 feet) for at least 1 year were reviewed to gauge the effect of altitude on 2-mile running performance. An average of 48 additional seconds (a 5% increase in time) was required to complete the run compared to sea level values in the same subjects. Run times gradually diminished during the first 9 months of assignment to altitude before stability was established. These data indicate that acclimatization occurs over several months. Even with acclimatization, substantial loss of performance is associated with habitation at intermediate altitude. PMID- 1454174 TI - Serum gentamicin concentrations in postpartum endomyometritis. AB - Gentamicin in combination with other antibiotics is frequently used in the treatment of postpartum endomyometritis. The need to monitor and maintain therapeutic concentrations, however, is controversial. To assess the role of monitoring, serum gentamicin concentrations were prospectively studied in an obstetric population treated for postpartum endomyometritis. Clinical course was correlated to serum gentamicin levels obtained using a 1 mg/kg/dose regimen. No patient demonstrated therapeutic concentrations. Sixteen of 18 obstetric patients (88%) exhibited a clinical response despite subtherapeutic serum gentamicin concentrations. The two failures included one case of septicemia and one wound seroma. Serum gentamicin levels of this obstetric population when compared to those from a gynecologic population treated for benign disease demonstrated no statistical difference. These data suggest that clinical response provides an accurate indication of the efficacy of therapy and that gentamicin doses of 1 mg/kg/dose provide sufficient antibiotic coverage in most cases. These results do not support the use of increased gentamicin dosages and the need to attain therapeutic levels in the obstetric patient, as previously suggested. PMID- 1454175 TI - Thirty years of experience with infectious hepatitis prevention in the Israel Defence Forces. AB - Infectious hepatitis is endemic to Israel. Large outbreaks of infectious hepatitis were common in the Israel Defence Forces (IDF) before 1970, at which time post-exposure prophylaxis with immune serum globulin was introduced. It caused a decrease in the incidence of infectious hepatitis from 10-14/1,000 to 3/1,000. A further reduction in incidence was achieved after 1978 when a policy of pre-exposure prophylaxis was established. The number of yearly outbreaks and cases per outbreak also declined as a result of this policy. Worldwide studies have shown that a policy of pre-exposure prophylaxis and/or post-exposure prophylaxis with immune serum globulin is effective in reducing the incidence of infectious hepatitis. The experience of the IDF is that a combination of both pre exposure and post-exposure prophylaxis is more efficacious. This policy should be worthwhile in other areas where infectious hepatitis is endemic. PMID- 1454176 TI - Emotional distress in chronic medical illness: treatment with time-limited group psychotherapy. AB - Time-limited (12 sessions) group psychotherapy was provided for 14 patients with a variety of serious medical illnesses. All patients were referred for psychiatric assistance and most had minimal or no psychiatric disorder. Patients not terminally ill, in continuous pain, or cognitively impaired, but otherwise unselected, were offered treatment. Emphasis was placed on validation of feelings, interpersonal understanding, and problem solving. Increased sense of well being was noted in all patients by self-report; this was contrasted by findings on the Millon Behavioral Health Inventory indicating generally sustained somatic concern. A moderate reduction in the number of visits to other clinics was noted during the treatment period. Although outcome data are incomplete, this appears to be a useful and cost-effective treatment for mixed groups of emotionally distressed medical patients. PMID- 1454177 TI - Anthropometric, psychomotor, and hemodynamic changes during twenty-one continuous days of eating only meals, ready-to-eat (MREs). AB - This study investigated anthropometric, psychomotor, and hemodynamic changes in young adult men during 21 continuous days of eating only meals, ready-to-eat (MREs). The MRE diet group lost more weight and bodyfat (significant at abdominal site, total skinfolds, and total bodyfat percent), and had significantly greater gains in hand grip strength than did controls. Results support the contention that, when eaten as designed, MREs are nutritionally adequate for maintaining body weight and muscle strength without adverse effects. PMID- 1454178 TI - The value of dental radiographic equipment in a Navy field hospital. AB - The portable dental X-ray machine has been used to augment standard field x-ray equipment. This allows for more rapid assessment of combat casualties. The data presented describe the use of the portable dental X-ray machine during the 100 hour ground war against Iraq. PMID- 1454179 TI - Soldiers' dental complaints compared with clinical findings in the Military Hospital in Bologna, Italy. AB - There is no previous data published on the frequency and reasons for dental emergencies in the Italian Army. In this study, all the 329 soldiers who sought dental help during a 5-month period in the Military Hospital in Bologna were investigated. Prior to clinical examination, the soldiers filled out a questionnaire concerning their subjective perception about their dental treatment needs. Data from the questionnaire were then compared with the actual status findings. The results showed that endodontic problems comprised the majority of the cases (37.1%), followed by surgical problems as the second most frequent emergency (33.1%). The subjects' own perceptions showed good agreement with the clinical record in cases with endodontal or surgical problems, excluding problems related to wisdom teeth, while those related to caries and periodontal disease were less frequently correctly assessed by the soldiers. PMID- 1454180 TI - Establishing a neurology service in support of Operation Desert Storm. AB - As a result of Operation Desert Storm, a neurology service was established in the Fort Leonard Wood MEDDAC. Between January 1 and April 30, 1991, a total of 315 new neurology patients were seen in consultation. This number plus all the follow up visits add up to a total of 750 clinical encounters during that period. The characteristics of this service (population served, reasons for referral, and diagnoses) were not significantly different than has been previously reported. The level of activity, by MS3 standards, qualifies this MEDDAC to have two neurologists. PMID- 1454181 TI - Behavioral differences of irradiated persons associated with the Kyshtym, Chelyabinsk, and Chernobyl nuclear accidents. AB - Three nuclear accidents besides Chernobyl have occurred in the former Soviet Union. The accidents occurred around Kyshtym and Chelyabinsk in the Ural Mountains between 1949 and 1967 and contaminated over one-half million people. The health ministries are now interested in the data previously collected on these irradiated populations in order to examine the health (e.g., psychological, hereditary, genome damage, etc.) implications of long-term radiation exposure. PMID- 1454182 TI - A retrospective analysis of open fractures sustained by U.S. military personnel during Operation Just Cause. AB - A retrospective analysis was conducted of 37 open fracture cases sustained by U.S. military personnel during the recent low-intensity conflict in Panama (Operation Just Cause). The etiology, location, classification, and management of open fractures sustained in combat is presented. A significant difference was noted in the infection rate for type III open fractures that were debrided in Panama (22%) as compared to those that were debrided only after transport to CONUS (66%). This study supports the critical importance of adequate battlefield surgical support in low-intensity conflicts, and reemphasizes the crucial role of early surgical debridement for the prevention of wound infection. PMID- 1454183 TI - Carpal tunnel syndrome associated with histoplasmosis: a case report and literature review. AB - A case of localized Histoplasma capsulatum flexor tenosynovitis causing a carpal tunnel syndrome is presented. Carpal tunnel release, with tenosynovectomy, was performed followed by antifungal therapy. The symptoms did not recur. Tenosynovectomy followed by antifungal treatment is recommended. PMID- 1454184 TI - Kaposi's sarcoma of the gallbladder. AB - A 30-year-old man with symptomatic acquired immunodeficiency syndrome presented with abdominal pain and disseminated intravascular coagulation. Radiographic studies revealed thickening of the gallbladder wall. Following stabilization of the coagulation disorder, the patient underwent a cholecystectomy, and the gallbladder was found to contain Kaposi's sarcoma (KS). There have been no previously published reports of KS found in the gallbladder of a living patient in the absence of cutaneous manifestations of KS. The current case illustrates that KS is a multi-focal systemic disease which may have extracutaneous primary manifestations. PMID- 1454185 TI - Idiopathic renal hematuria in a military working dog. AB - A 1.5-year-old male Belgian Malinosis Military Working Dog presented with a 1 month history of intermittent hematuria. Diagnostic ultrasound and contrast radiography demonstrated large blood clots in the urinary bladder and a filling defect in the right renal pelvis. At surgery, clotted blood was present in the right ureter and bladder. Following right nephrectomy, the dog returned to training. One month later, elevations in urea nitrogen and creatinine were noted. Hematuria recurred at 3 months and the dog was found dead in its kennel. Necropsy showed a blood-filled left renal pelvis and ureter. PMID- 1454186 TI - Knee protection during Ranger school. PMID- 1454187 TI - Chronic fatigue syndrome and military service. PMID- 1454188 TI - Antidepressant use for idiopathic hypersomnolence. PMID- 1454189 TI - Arthroscopic surgery of the knee on the U.S. Naval Hospital Ships during Operation Desert Shield. AB - Between September 1990 and January 1991, while deployed to the Persian Gulf for Operation Desert Shield, 118 patients underwent arthroscopic surgery of the knee on the U.S. Naval Hospital Ships USNS Mercy and USNS Comfort. There were 113 men and 5 women, with an average age of 28 years (range, 19-59 years). The most common findings at the time of arthroscopy were meniscus tears (53%), anterior cruciate ligament tears (29%), and normal arthroscopic examinations (9%). There were three complications, two hemarthroses and one superficial portal site infection. Seventy patients (59%) were able to be returned to duty at an average of 6 days post-operatively, obviating the need to evacuate these patients out of the Middle East theater to Europe or the United States, thus avoiding additional delay, expense, and loss of the service member to his military unit. PMID- 1454190 TI - Medical limitations of gas masks for civilian populations: the 1991 experience. AB - Using a gas mask (GM) may involve considerable inconvenience, impairment of respiration and communication, and serious psychological reactions. The medical literature is primarily focused on the occupational aspects of using the GM by young and healthy workers. In contrast, there is hardly any information concerning the use of GMs by large, unselected populations, including children, the elderly, and the sick. Issuing GMs to all residents of Israel prior to Operation Desert Storm created an urgent need to define the populations whose health might be jeopardized by using the standard GM. Adding an active air supply system (AASS) to a standard GM may ease the burden on this high-risk group. We evaluated the physiological aspects of breathing with a GM, with and without AASS, in respect to pathophysiology of diseases, and reached a set of criteria for identifying those who may be endangered by a GM and are expected to benefit from the AASS. The method used to sort and identify those entitled to the AASS is described. PMID- 1454191 TI - Physical and psychosocial impact of activation and deactivation on Army Reserve nurses. AB - Reserve mobilization training focuses on specialty skills and soldiers' common tasks, but does not prepare individuals for the physical and psychological realities of activation. The purpose of this descriptive, multiphasic research was to systematically examine, as it was experienced, the impact of activation and subsequent de-activation on 81 Army Reserve nurses. The variables measured included somatic symptoms, psychosocial effects, stressors, coping strategies, and positive aspects of the experience. Some nurses experienced physical and psychosocial symptoms consistent with post-traumatic stress disorder. Lessons learned from this study will help Army Reserve units to be more proactive in mobilization preparation and training. PMID- 1454192 TI - Research priorities of VA nurses: a Delphi study. AB - The purpose of this study was to conduct a Delphi survey of a sample of Gainesville Veterans Affairs Medical Center staff and head nurses. The study consisted of three rounds of questionnaires completed by the nurses as they identified and narrowed the most pressing nursing research questions. Results indicated that in five of the six clinical settings, despite investigators' instructions to identify clinical nursing research questions, administrative research questions were identified and ranked consistently higher in priority than clinical research questions. The single exception was in home care, where clinical questions received the highest priority. This phenomena may suggest that institutional constraints interfere with nurses' full expression of their clinical practice. PMID- 1454193 TI - Efficiency in the pediatric orthopedic clinic and the effect on the parents: a comparison of military and civilian medical centers. AB - In a short-term comparison of similar pediatric orthopedic practices at a military and a civilian institution in the same geographical location, it was found that total appointment time, waiting time, and travel time were longer in the military setting. It appeared, however, that there was more leniency toward time off from work to accompany children to appointments in the military population. These factors may have considerable impact on time lost from the job for service member sponsors. PMID- 1454194 TI - The efficacy of medicine during the campaigns of Alexander the Great. AB - This paper examines the various factors that may have determined the efficacy of physicians during the campaigns of Alexander the Great. Such general variables as the adequacy of preparation, the nature of the medical profession, and the extent of preventative measures are all discussed at the outset of the paper, followed by a more detailed examination of the specific wounds, illnesses, and treatments of Alexander as described in the accounts of the Alexander historians Plutarch, Curtius, and Arrian. Where no remedy is given by these writers (as is usually the case), this paper speculates on the efficacy of possible treatments as advocated in the contemporary Hippocratic corpus. Casualty statistics of the campaigns are compared to a similar review of Homer's Iliad. From these examinations, this paper concludes that wound treatment efficacy was significantly greater than that of illness treatment, and that Alexander lost many more men to disease than to the wounds of war. PMID- 1454195 TI - Utilization review in the military health care delivery system. PMID- 1454196 TI - Noise-induced low- and high-frequency hearing losses in Finnish conscripts. AB - Thirty-nine otologically healthy military conscripts were examined at the beginning and at the end of their 1-year service. On entry, they all showed normal findings during clinical otolaryngological examinations. The test battery included both conventional (0.25-8 kHz) and high-frequency "electric bone conduction" (0.5-20 kHz) audiometry (EBC). The median pure-tone right ear thresholds at the end of service were 5 dB worse over the frequency range of 2-8 kHz compared with the thresholds at the beginning of the service. The difference was statistically highly significant (p = 0.00035). The median left ear pure-tone thresholds at frequencies of 0.25, 2, and 8 kHz were 5 dB worse at the end of the service compared to the thresholds at the beginning of the service. However, the difference was not statistically significant (p = 0.23). The median curves for the high-frequency (EBC) thresholds measured after the service showed worse thresholds over the whole frequency range compared to the median curves measured before the service. The greatest difference was seen in the highest frequencies (15-17 kHz) in both ears. The differences were statistically significant in both ears (p = 0.03 in the right ears; p = 0.01 in the left ears) when threshold values over the whole frequency range were analyzed. Since the otolaryngological history of these conscripts was uneventful during their service, the hearing deteriorations were considered to be caused by shooting practice. PMID- 1454198 TI - The medical challenge of military operations in the Mississippi Valley during the American Civil War. AB - The prevention and treatment of disease was as important as combat operations in the campaigns along the Mississippi River during the American Civil War. Throughout the Vicksburg campaign, many more soldiers were disabled by sickness than by combat injury. While this held true for both sides, a greater proportion of the Union army was healthy than of the opposing Confederate force. In the last 2 years of the war, the North tried to occupy the Confederate states in the Mississippi Valley. The failure to accomplish this goal was partly due to the deteriorating health of the Union army. Medical knowledge and action taken to prevent disease were of major importance in the success and the failure of military campaigns in the Mississippi Valley during the American Civil War. PMID- 1454197 TI - Epidemiology of soft-tissue/musculoskeletal injury among U.S. Marine recruits undergoing basic training. AB - We determined the incidence of soft-tissue/musculoskeletal injury occurring during 8,076 recruit-months at risk among recruits undergoing basic training at Marine Corps Recruit Depot, San Diego, California, between January and April 1990. We analyzed International Classification of Disease codes relating to initial visit for injuries, and calculated recruit-months from weekly strength figures. Training-related injuries occurred at a rate of 19.9 injuries per 100 recruit-months. Within the sports medicine clinic, iliotibial band syndrome (22.4%), patellar tendinitis (15.1%), and mechanical low back pain (11.4%) occurred most frequently, with rates per 100 recruit-months of 2.1, 1.4, and 1.1, respectively. PMID- 1454199 TI - USAR Nurse Referral and Retention Program. AB - In 1987, the 804th Hospital Center made alleviating the shortfall of registered nurses in the Command a priority. The Command had only 79% of its registered nurse positions filled at the time. Using the recruitment strategies of an employee referral program and a mailing list, the Command reached 100% fill in 2 years and maintained those gains for an additional year. Retention strategies were also implemented which lowered the attrition rate. This paper describes the Army Nurse Referral and Retention Program developed and implemented at the 804th Hospital Center that relieved the shortfall of registered nurses in the United States Army Reserve in New England. PMID- 1454200 TI - High-grade immature teratoma of the testis in infancy. AB - Teratomas of the testis in infants are rare tumors which often display immature elements, disturbing in their histologic appearance. Although the presence of similar histologic features worsens prognosis in testicular teratomas in adults and in teratomas of infants and children presenting at other anatomic sites, the presence of immature elements in testicular teratomas of infancy does not appear to affect prognosis. Therefore, orchiectomy alone is adequate therapy for these neoplasms. The case of an 8-month-old infant with a teratoma of testis is presented. PMID- 1454201 TI - Acute trauma and hypnosis. AB - Hypnosis is a valuable adjunct to the management of acute trauma. This is a case presentation of the management of severe burn injuries after fire and explosion on a United States Navy vessel. Hypnosis was used to calm one patient and facilitate intubation. Further suggestions of rapid healing and anxiety control were given. Hypnosis is not only helpful for management, but can be used to decrease the perceived severity of the incident. Patient well-being may also prevent sequelae of stress. PMID- 1454202 TI - Distribution of 5-HT1 binding sites in cat spinal cord. AB - Quantitative analysis of high affinity [3H]5-HT binding to 5-HT1 receptors in the cervical, thoracic, lumbar, and sacral spinal cord of the cat revealed specific binding throughout the grey matter, with the highest levels of binding in laminae II and III, and the lowest levels in laminae I and VII. Relatively high levels were also observed in the thoracic intermediolateral cell column. There were no significant differences in the degree of binding between various segmental levels. Comparison of these data with published maps of 5-HT immunoreactivity reveals--with the exception of lamina I--a close correspondence between the degree of immunoreactivity and the degree of 5-HT binding. These results suggest that 5-HT plays an important role in a variety of spinal cord sensory, motor and autonomic functions. PMID- 1454203 TI - L-threo-3,4-dihydroxyphenylserine enhanced ocular dominance plasticity in adult cats. AB - We studied whether ocular dominance plasticity can be restored to the aplastic visual cortex of the adult cat by peripheral administration of L-threo-3,4 dihydroxyphenylserine (L-threo-DOPS), an exogenous precursor of L-noradrenaline (NA). We found that NA output in the visuocortical dialysate was significantly increased by a single administration of L-threo-DOPS (200 mg or 1 g, i.p.). Single unit recordings revealed a significant reduction of binocular cells (binocularity = 0.30) in juvenile cats (7-8 months of age) that had been monocularly deprived for one month in combination with L-threo-DOPS (200 mg/day, per os). These results suggest that peripheral administration of L-threo-DOPS enhances ocular dominance plasticity, presumably through activation of the central noradrenergic system. PMID- 1454204 TI - Pyruvate dehydrogenase dephosphorylation in rat brain synaptosomes and mitochondria: evidence for a calcium-mediated effect in response to depolarization, and variations due to ageing. AB - The phosphorylation state of P42, the phosphorylated, catalytically inactive, alpha-subunit of pyruvate dehydrogenase (PDH), decreased markedly (42.4%) in response to K(+)-depolarization of synaptosomes. The dephosphorylation was rapid (5-15 s), calcium-dependent and could also be observed in isolated mitochondria exposed to a rise in extramitochondrial calcium, suggesting that P42 dephosphorylation may act as a calcium sensor in the mitochondrial matrix. The depolarization-dependent dephosphorylation rate of P42 was decreased in synaptosomes derived from 24-month-old animals with respect to 3-month-old adults. The relevance of these results in terms of PDH activation during ageing is discussed. PMID- 1454205 TI - Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. AB - Reduced and oxidized glutathione concentrations in post-mortem brain tissue from the substantia nigra of control subjects and patients with neuropathologically confirmed Parkinson's disease were measured by a coulometric method using high pressure liquid chromatography and electrochemical detection. Reduced glutathione concentrations were decreased in the substantia nigra of parkinsonian patients compared with controls. Differences in the concentration of oxidized glutathione and in the percentage of oxidized glutathione of the total glutathione were not observed between parkinsonian and control subjects. The finding that oxidized glutathione is not decreased in Parkinson's disease suggests that the decrease in reduced glutathione is not exclusively the consequence of neuronal loss in the substantia nigra but may indicate a state of oxidative stress. PMID- 1454206 TI - Soybean agglutinin binds commonly to a subpopulation of small-diameter neurons in dorsal root ganglion, vascular endothelium and microglia in human spinal cord. AB - Soybean agglutinin (SBA) was used to identify the location of N acetylgalactosaminyl glycoconjugates in human dorsal root ganglia (DRG) and spinal cord. SBA bound to a subpopulation of small-diameter neurons in DRG and their central projections. It also bound to microglia and vascular endothelium. Vascular endothelium, DRG neurons and microglia do not originate from the neural tube, but penetrate into the neural tube in the embryonic stage and thereafter are located in the spinal cord. SBA binding glycoconjugates may be responsible for cell-cell interaction between these three cell types and tissues in human spinal cord. PMID- 1454207 TI - Nuclear localization of estrogen receptor-immunoreactivity in the preoptic area of female rats and its reduction by intraventricular colchicine treatment. AB - The subcellular localization of estrogen receptor (ER) was investigated in the preoptic area of ovariectomized female rats by electron microscopic immunohistochemistry, using a monoclonal antibody to ER. ER-immunoreactivity was localized in the nuclei of neurons of the periventricular preoptic nucleus (Pe) and the medial preoptic area (MPA). ER-immunoreactivity had a speckled pattern in the nucleus, but was not observed in the nucleolus or cytoplasm. After intraventricular colchicine treatment, ER-immunoreactivity within the nucleus was reduced drastically in neurons of the Pe and the MPA. The possible mechanism by which colchicine alters ER-immunoreactivity is mentioned. PMID- 1454208 TI - Late appearance of parvalbumin-immunoreactive neurons in the rodent cerebral cortex does not follow an 'inside-out' sequence. AB - Parvalbumin (PARV), a Ca(2+)-binding protein believed to play a role in neuronal excitability, is contained in certain GABAergic inhibitory neurons of the cerebral cortex. Here we report that expression of PARV in the developing neocortex of rats and mice occurs with a sequence which does not follow the usual 'inside-out' gradient of cortical development. Thus, PARV-immunoreactive neurons appear first in layer V and only thereafter in the remaining cortical layers. An adult-like pattern of immunoreactivity is reached simultaneously in layers II-III and VIb. These observations indicate that the mechanisms regulating the functional maturation of PARV-containing inhibitory neurons are different from those that generally govern developmental processes in the cortex. PMID- 1454209 TI - Inhibition of nitric oxide synthesis does not reduce infarct volume in a rat model of focal cerebral ischaemia. AB - The effect of the nitric oxide (NO) synthesis inhibitor Ng-nitro-L-arginine methylester (L-NAME) on ischaemic brain damage was determined in a rat model of focal cerebral ischaemia. Ischaemia was induced by permanent occlusion of the left middle cerebral artery (MCA) and infarction assessed 4 h post-occlusion by quantitative histopathology. L-NAME (30 mg/kg s.c.), administered 30 min pre- and 30 min post-MCA occlusion, did not significantly alter the volume of ischaemic damage in the cerebral hemisphere, neocortex or caudate nucleus compared with saline controls. This result provides no support for the view that NO generation is a key component in the post-ischaemic cascade leading to acute neuronal death. PMID- 1454210 TI - Central 6-hydroxydopamine lesions decrease mineralocorticoid, but not glucocorticoid receptor gene expression in the rat hippocampus. AB - The role of hippocampal noradrenergic inputs in the modulation of corticosteroid receptor expression has been investigated. Adult male rats were given central 6 hydroxydopamine (6-OHDA) and the expression of hippocampal mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNA was examined after two weeks by in situ hybridization histochemistry. Expression of MR mRNA was significantly decreased in all subregions of the hippocampus except CA2, but 6-OHDA lesions had no effect on GR mRNA expression. These data reveal differential regulation of the two receptor types by noradrenergic inputs. PMID- 1454211 TI - Evidence for sex steroid receptors in feline brainstem. AB - Specific binding sites for estrogens, androgens, and progestins were found in cytosol from perfused cat brainstem with the use of a steroid binding assay. These sites resemble 'classical' steroid receptors in ligand specificity as well as in sedimentation properties (sedimentation constant 8-10S on sucrose density gradient). The presence of estrogen receptor in brainstem extracts was also confirmed by an enzyme immunoassay employing monoclonal antibodies directed against human estrogen receptor. This finding may be relevant to known influences of sex steroids on respiration. PMID- 1454212 TI - Absence of a daily neuronal rhythm in the suprachiasmatic nuclei of acircadian Djungarian hamsters. AB - The suprachiasmatic nuclei (SCN) in mammals generate and maintain a variety of daily rhythms. In nocturnally active rodents, SCN electrical activity is high during the subjective day (that time of locomotor inactivity) and low during the subjective night. The present experiment examines the relationship between SCN neuronal activity and the expression of overt circadian behavior in the Djungarian hamster (Phodopus sungorus). Wheel-running locomotor activity was measured in 2 groups of hamsters housed in constant dark (DD). Twelve hamsters, selected from ongoing experiments in our laboratory, showed no overt circadian rhythm in locomotor activity. A second group of 9 control animals exhibited rhythmic wheel-running activity in DD. In contrast to control animals, in vitro SCN electrical activity in brain slices prepared from acircadian hamsters showed no circadian variation. These data indicate that in acircadian animals SCN electrical activity properly reflects behavioral patterns. PMID- 1454213 TI - The stability of human eye orientation during visual fixation. AB - Using the magnetic search coil technique, gaze stability in the horizontal, vertical and torsional planes was measured binocularly in human subjects during visual fixation. Horizontal and vertical eye rotations exhibited a mixture of slow drifts and resetting microsaccades yielding an average standard deviation of 0.11 and 0.10 deg, respectively. In contrast, torsional rotations showed unsystematic smooth drifts with fewer saccades yielding an average standard deviation of 0.18 deg. The lower precision of gaze control in the torsional plane may reflect (i) a discrepancy between the encoding of retinal images in two dimensions but of ocular motor control signals in three dimensions, and (ii) the visual consequences of ocular drifts in the torsional plane, which differ from those in the horizontal and vertical planes. PMID- 1454214 TI - Thermal sensitivity and effect of temperature acclimation on ocular serotonin N acetyltransferase activity in Rana perezi. AB - The thermal sensitivity and the response to thermal acclimation of the serotonin N-acetyltransferase (NAT) activity in frog ocular tissue were studied. The ocular NAT shows a positive thermal modulation for both cosubstrates (tryptamine and acetyl-CoA). The higher NAT activity in the cold-acclimated group (4 degrees C) with respect to the warm-acclimated one (24 degrees C) implies a partial thermal compensation of the enzyme. The present results suggest that frog ocular NAT response to temperature entails a modulation of thermal sensitivity of the enzyme rather than changes in enzyme concentration. PMID- 1454215 TI - Modifications of ependymal cells membranes by galactocerebrosides in cell culture. AB - In this paper we have demonstrated that treatment of ependymal cells in culture by galactocerebrosides induced a decrease in plasma membrane fluidity and an increase of EGF binding sites. We have shown in a previous work that galactocerebroside in vitro and in vivo caused an important morphological change in ependymal cells that grew into an astrocytic shape after a five day treatment. We discuss the hypothesis that the first event in morphological effect could be a modification of plasma membrane followed by important changes in molecules distribution. PMID- 1454216 TI - Effects of thiorphan, bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the recovery of neurotensin and neuromedin N released from mouse hypothalamus. AB - The effects of the endopeptidase 24.11 ('enkephalinase') inhibitor thiorphan, the aminopeptidase inhibitor bestatin and a novel metallopeptidase inhibitor JMV 390 1 on the K(+)-evoked release of immunoreactive neurotensin and neuromedin N (iNT and iNN) from mouse hypothalamic slices were examined. (JMV 390-1 inhibits several metallopeptidases including endopeptidases 24.11, 24.15 and 24.16, and aminopeptidase N equipotently with Ki values around 50 nM.) Thiorphan increased the recovery of released iNT nearly 2-fold and had no effect on iNN. Bestatin produced a 4-fold increase in iNN recovery and was inactive on iNT. Finally, iNT and iNN recoveries were increased up to 4- and 5-fold, respectively, by JMV 390 1. These results show that in the mouse hypothalamus endopeptidase 24.11 participates with other metalloendopeptidases to the degradation of endogenously released NT while endogenously released NN is principally degraded by aminopeptidase(s). PMID- 1454217 TI - Potentiation of spontaneous synaptic activity in rat mossy cells. AB - Recent studies have demonstrated the vulnerability of dentate mossy cells to seizure-induced damage. One source of potentially damaging synaptic input are spontaneously active granule cell terminals ('mossy terminals'.) We sought to test whether there were activity-dependent changes in the spontaneous excitatory input to mossy cells. Using the in vitro slice preparation, we examined the frequency and amplitude of spontaneous excitatory postsynaptic potentials (EPSPs) after intracellular current injection designed to mimic the extreme depolarization these neurons receive during repetitive afferent stimulation. In 4 of 7 neurons, depolarization with trains of current pulses resulted in a significant and persistent increase in frequency of spontaneous synaptic depolarizations (to an average of 178% of the initial baseline rate). In 3 of these affected neurons, an increased frequency of large amplitude, fast-rising EPSPs accounted for the majority of this change. Injection of hyperpolarizing current pulses failed to alter spontaneous activity in 3 other mossy cells. These results suggest spontaneous synaptic input to mossy cells in plastic and can be potentiated by depolarization of a single postsynaptic mossy cell. The ability of mossy cells to potentiate their excitatory input may be relevant to their vulnerability to excitotoxic injury during repetitive afferent stimulation. PMID- 1454218 TI - Delayed increase of extracellular arginine, the nitric oxide precursor, following electrical white matter stimulation in rat cerebellar slices. AB - Amino acid levels were measured in perfusates from biplanar slices of rat cerebellum installed in a Krebs-filled three-compartment chamber. The two lateral compartments housed the white matter and a section containing parallel fibres respectively. The central compartment housed cortical structures, including the Purkinje cell and granule cell bodies. This arrangement allows selective electrical stimulation of the parallel fibre or mossy fibre pathways, recording of the evoked responses to such stimulation and collection of the perfusion medium passing through the central chamber for amino acid analysis using high pressure liquid chromatography (HPLC). Both, 2-Hz and 5-Hz stimulation of white matter caused a delayed increase in arginine levels in the perfusate. Since L arginine is the physiological precursor of nitric oxide, a neuronal messenger in the brain, the data suggest that physiological stimuli can result in the release of this precursor, possibly to supply the nitric oxide synthase. PMID- 1454219 TI - Polyamine-sensitive binding of [125I]ifenprodil in washed, frozen-thawed synaptic membranes: evidence for high affinity binding requiring an open NMDA channel. AB - Binding of [125I]-labelled ifenprodil, a non-competitive N-methyl-D-aspartate (NMDA) antagonist acting at the polyamine domain, was studied in washed, frozen thawed synaptic membranes. Under these conditions where the NMDA channel is essentially in a closed channel state and in the presence of GBR 12909, [125I]ifenprodil binding was rapid, reversible, stereospecific, saturable and to a single population of sites (Kd 76 microM, Bmax 140 nmol/mg protein). Binding was inhibited by spermine, spermidine and ifenprodil congeners. These characteristics differed from those found in fresh membranes (open channel state), with ifenprodil congeners being less potent and potencies of polyamines being unchanged. These data suggest independent, but interacting sites for polyamines and ifenprodil congeners, the latter sensitive to endogenous modulators, labelled by [125I]ifenprodil and probably not NMDA-linked. High affinity binding of ifenprodil congeners seems likely to require an open ('activated') NMDA channel. PMID- 1454220 TI - Localization of dopamine D2 receptor mRNA with non-radioactive in situ hybridization histochemistry. AB - A digoxigenin-labeled antisense 42-mer oligonucleotide was used for the localization of the dopamine D2 receptor mRNA in the rat brain. The digoxigenin label was identified with alkaline phosphatase conjugated sheep-anti-digoxigenin. In good analogy with the known terminal fields of the dopaminergic system, various nuclei throughout the brain were labeled. Positive in situ hybridization signals were also found in dopamine cell groups of the substantia nigra and ventral tegmental area and in regions where a dopaminergic innervation is controversial, like the cerebellar cortex and the hippocampus. The non radioactive in situ hybridization procedure described, shows the localization of the dopamine D2 receptor mRNA with a very high contrast and an optimal histological resolution. PMID- 1454221 TI - Bilateral destruction of neocortical and perirhinal projection targets of the acoustic thalamus does not disrupt auditory fear conditioning. AB - The present study examined whether complete bilateral destruction of auditory cortex would interfere with auditory fear conditioning in rats. Complete destruction of auditory cortex required lesions of temporal neocortical and perirhinal periallocortical areas. Fear conditioning was assessed by measuring freezing and arterial pressure responses elicited by an acoustic stimulus after pairing with footshock. Animals with complete bilateral lesions of auditory cortex showed conditioned arterial pressure and freezing responses comparable to those of unoperated controls. In contrast, bilateral destruction of the acoustic thalamus interfered with the conditioning of both responses. These results demonstrate that the auditory cortex is not required for the conditioning of fear responses to simple acoustic stimuli and add to the growing body of evidence that fear conditioning can be mediated by subcortical (amygdaloid) projections of the acoustic thalamus. PMID- 1454222 TI - Origin of luteinizing hormone-releasing hormone (LHRH) neurons in the chick embryo: effect of the olfactory placode ablation. AB - A unilateral olfactory placodectomy resulted in the absence of luteinizing hormone-releasing hormone-immunoreactive (LHRH-ir) cells in the olfactory forebrain axis of the operated side, whereas the development of the LHRH neuronal system was not disturbed on the unoperated side. In the embryos in which a fragment of the medial olfactory epithelium was spared the damage, a small number of LHRH-ir cells were detected in the nasal region of the operated side, where the lack of the central projection of the olfactory nerve caused stagnation of LHRH-ir cells, no ir-cells being found in the brain area. These results suggest that LHRH neurons originate in the olfactory placode and then migrate into the forebrain along the olfactory nerve. PMID- 1454223 TI - Cholinergic fiber loss occurs in the absence of synaptophysin depletion in Alzheimer's disease primary visual cortex. AB - The significance of cholinergic degeneration in Alzheimer's disease (AD) depends, in part, on whether it is an early event, possibly integral to the progression of the disease, or a late event, occurring only as a secondary effect of cortical degeneration. We have been studying the primary visual cortex in AD cases, on the assumption that the disease process may be retarded in this relatively-spared area, thus providing a 'window' on early AD. In this work, we have quantified acetylcholinesterase fiber density and the density of an immunohistochemical reaction for synaptophysin as measures of cholinergic and total synaptic loss, respectively, in the primary visual cortex of AD and control cases. Cholinergic fibers were depleted to 15% of control values, while synaptophysin density was not significantly altered. Cholinergic degeneration thus appears to occur in the absence of generalized synaptic loss in this area. PMID- 1454224 TI - Evidence for increased calcium influx across the choroid plexus following brief ischemia of gerbil brain. AB - Following 5 min ischemia of gerbil brain, unidirectional transfer of calcium from plasma to cerebrospinal fluid was measured quantitatively with 45CaCl2 at 4 days postischemic recirculation. 45Ca influx across the choroid plexus increased significantly from 0.0101 +/- 0.001 min-1 measured in sham-operated animals (n = 15) to 0.0294 +/- 0.002 min-1 determined in ischemic animals (n = 21; P less than 0.05). Histological examination of choroid plexus was carried out in Cresyl violet-stained sections from gerbils subjected to 5 min ischemia followed by 4 days (n = 6) and 7 days (n = 7) postischemic recirculation. Increased calcium transfer to cerebrospinal fluid was associated with cell damage of choroid plexus observed at 4 days postischemia. Endothelial choroid plexus injury was still detectable at 7 days after the ischemic insult suggesting a long-lasting pathomorphological process. Postischemic alterations in choroid plexus functions apparently expose brain tissue to much higher calcium influx into cerebrospinal fluid which, in turn, may contribute to calcium-related cell damage of the central nervous system. PMID- 1454225 TI - The old system of academia is toppling. PMID- 1454226 TI - Neonatal NP graduate education. PMID- 1454227 TI - Letter to Dr. Louis Sullivan: "my husband Ed retired from the N.Y. telephone company. I am a retired public health nurse". PMID- 1454228 TI - Red ribbons: verity or vogue? PMID- 1454229 TI - From anxiety to action: facilitating faculty development during curriculum change. AB - Nurse educators, both as individuals and as faculty collectively, have recognized the need for change. But as anyone with a basic knowledge of change theory knows, change is usually accompanied by varying degrees of resistance. PMID- 1454230 TI - A new age ISM: beyond a toxic apple. AB - Munhall argues for a synthesis and respect for various educational pedagogues, acknowledging the core values and beliefs about education that reflect our infinite variety. The article abandons the myth of the handsome prince and is the second of a trilogy on apples. PMID- 1454231 TI - Using qualitative methods in teaching undergraduate students research. PMID- 1454232 TI - Voting the RN ticket. PMID- 1454233 TI - AIDS agenda advanced. PMID- 1454235 TI - Medical book collecting: a retrospect and a forecast. AB - Medical book collecting and historical research are complementary pursuits. The author summarizes the contributions of bibliophiles who used their collections as a source of inspiration for historical studies and addresses the challenges confronting medical book collectors. PMID- 1454236 TI - Heirs of Osler: medical bibliophiles in America. AB - An heir is one who appears to acquire a trait from a predecessor or carries on his tradition. The author presents details about the great bibliophiles who received their stimulus from William Osler, his associates, or his writings. William Osler influenced the formation of private libraries in the United States. PMID- 1454234 TI - The legacy of New Jersey physician book collectors. AB - This article offers a brief history of the development of New Jersey's major history of medicine collection, and an overview of selected resources currently available to researchers. Old and rare medical books now are available to a new generation of physicians and scholars. PMID- 1454237 TI - CLIA-88 final rule: Part 3. AB - Physicians performing laboratory tests must have a registration certificate as of September 1, 1992. To continue testing without this certificate could lead to large fines and possible prosecution. This article covers quality assurance, quality control, and maintenance of instruments. PMID- 1454238 TI - Case report: malignant mesenchymoma of the mediastinum. AB - Malignant mesenchymoma is a malignant tumor arising in the soft tissues of the body. It is a rapidly growing tumor prone to recurrences and occasional metastasis. It occurs at all ages and locations but has a preference for the extremities and the retroperitoneum. PMID- 1454239 TI - Profiles in medicine: tribute to Oscar Auerbach, MD. AB - He is prepared to lecture on lung pathology. Instead, Dr. Oscar Auerbach discusses the role of the physician in society and what tremendous contributions each student has the potential to make. This speech re-energizes second-year medical students every year. PMID- 1454240 TI - Challenges for teachers of women's health. AB - Until recently, nursing literature had not addressed feminist issues and nurse educators have had little experience in programs of women's studies. The author discusses some implications for nurse educators as they relate to the new scholarship of women and a new consciousness of women's health. Factors contributing to the need for particular ways of teaching when dealing with women as students and with women's health experiences as subject matter are addressed. Using specific examples from her experience in teaching an open enrollment course in women's health, the author describes the use of some feminist pedagogical approaches and the students' response to them. PMID- 1454241 TI - Clinical case studies: a strategy for teaching leadership and management. AB - In the realities of clinical practice, BSN students are expected to demonstrate both clinical and managerial skills. Presenting leadership and management content through the use of complex patient situations in a clinical case study approach can assist in preparing them. This approach demonstrates to students that leadership and management is an integral part of professional practice. PMID- 1454242 TI - Public schools as a clinical setting for RN students. AB - The challenge to select meaningful clinical sites for RN students is a problem for educators. The significance of the public schools as an initial clinical site, the contribution of RNs to school health programs, student responses, and adaptations to the school setting are presented. Outcomes of the experience will interest nurse educators attempting to provide a professional education for RN to BSN students and provide a service to the community. PMID- 1454243 TI - Faculty support for gay and lesbian nursing students. AB - Gay and lesbian nursing students seem to be invisible. Because the color of their skin does not reveal their minority status, the decision whether to "come out of the closet" is a choice that must be remade-renegotiated-every day of the students' lives. Nursing faculty can play a pivotal role in supporting these students by their attitudes and activism. PMID- 1454244 TI - Students attend nurses association convention for college credit. AB - The author describes a college course that facilitates student attendance at the Iowa Nurses' Association (INA) convention and promotes observation of nurse leaders as they consider nursing and political issues. Using the guidelines in this article, nursing faculty can develop a similar course in their institutions and generate student interest in the activities of the state professional associations. PMID- 1454245 TI - Reciprocal learning among students in the clinical area. AB - Reciprocal learning is a cooperative, collegial method in which there is mutuality of student to student or student to faculty interaction, assistance, and benefits. This teaching method is congruent with curriculum revolution concepts. The authors describe reciprocal learning and provide an example of its application in the clinical area. Guidelines for implementation of the strategy are presented. PMID- 1454246 TI - A domino pharmacology review game. PMID- 1454247 TI - The teacher crisis in nursing education--revisited. AB - The nationwide shortage of teachers is severely and negatively impacting nursing. Many qualified applicants are being rejected by nursing schools, yet the quality of programs is jeopardized when faculty are hired with limited teaching experience and little, if any, formal education as teachers. The author reviews the development and status of graduate nursing education for teachers, documents strong arguments for increasing the number of graduate programs to prepare more teachers of nursing, and raises important questions about teacher education. PMID- 1454248 TI - Discomfort after peer administered injections in an on-campus laboratory. PMID- 1454249 TI - Leadership: a shifting paradigm. PMID- 1454250 TI - Three games for classroom instruction. AB - This article outlines three games appropriate for the education of student nurses. "Categories" is a question-answer type of bowl game. Team players earn points by correctly answering questions in selected areas of nursing content. "A Piece of the Pie" is a variation of a popular board game. Players fill in game "pies" which represent selected areas of nursing content by correctly answering questions. "Outburst" is a game consisting of two teams who accumulate a score by shouting out, in turn, items that they believe would be included under a topic heading. PMID- 1454251 TI - The doctor was Jekyll one minute, Hyde the next. PMID- 1454252 TI - When Mom goes back to school. PMID- 1454253 TI - A day of Thanksgiving. PMID- 1454254 TI - Evaluating A.S.T. and A.L.T. PMID- 1454255 TI - Examining the new O.S.H.A. regulation. PMID- 1454256 TI - A hand to hold. PMID- 1454257 TI - Watch your language. PMID- 1454258 TI - Recognizing neuroleptic malignant syndrome. PMID- 1454259 TI - Oral hypoglycemics: what you and your patient need to know. PMID- 1454260 TI - What you need to know about insulin injections. PMID- 1454261 TI - Billy wouldn't budge ... until the hard truth hit him. PMID- 1454262 TI - Caught in the cross fire. PMID- 1454263 TI - Heading off sudden cardiac death. PMID- 1454264 TI - Close-up on calcaneal fracture. PMID- 1454265 TI - Identifying the skin manifestations of H.I.V. PMID- 1454267 TI - Around the clock blood pressure monitoring: how to get good results. PMID- 1454266 TI - What to do when a patient becomes too special. PMID- 1454268 TI - A lethal injection: who's responsible? PMID- 1454269 TI - Epoetin alfa for renal and H.I.V.-positive patients. PMID- 1454270 TI - The performing art of nursing. PMID- 1454271 TI - The distinctiveness of nursing knowledge. PMID- 1454272 TI - Research methodology and nursing science. PMID- 1454273 TI - Is nursing pot-bound? PMID- 1454274 TI - Disciplinary perspective: unified or diverse? PMID- 1454275 TI - The nature of scientific truth. AB - The purpose of this article is to share with the readers the authors' views on the need for a philosophical foundation in nursing scholarship. The philosophical premises of realism, idealism, and empiricism are discussed. In addition, the research methods most appropriately used with each philosophical stance are identified and discussed. The authors strongly suggest that nursing epistemology will not advance along the lines of good science until all nursing theorists, thinkers, and philosophers identify their underpinning philosophical positions prior to the discovery of theory, through research and other scientific endeavors. A nursing science fiction account of discovery and theory is used to illustrate the points made within the article. PMID- 1454276 TI - Concepts from eastern philosophy and Rogers' Science of Unitary Human Beings. AB - A brief outline of Buddhist thought is presented. Four concepts from early Indian philosophy which contributed to the development of the middle way consequence (Madhyamika Prasangika) school of Tibetan Buddhist philosophy are discussed. These are: action (karma), direct perception, emptiness, and dependent arising. An overview of Martha Rogers' science of unitary human beings is given, followed by a discussion of the concepts of energy field and integrality within her worldview. Buddhist concepts of action, direct valid perception, and emptiness are considered in relation to Rogers' notion of energy field; the concept of dependent arising is compared to Rogers' principle of integrality. It is proposed that Rogers' worldview includes areas of similarity with concepts used in Tibetan Buddhist philosophy. PMID- 1454277 TI - The meaning of being an elder in Nepal. AB - The purpose of this qualitative descriptive research study was to explore the meaning of being an elder in Nepal. The nurse researcher, accompanied by an interpreter, travelled to six villages east and west of Kathmandu Valley to speak with 25 individuals about their experiences in later life. Questions structured within Parse's theoretical perspective guided discussions to uncover older persons' views of aging, their relationships with others, and the changes and hopes of daily life. Findings revealed that the meaning of being an elder in Nepal is "cherishing necessities for survival intermingles with the rapture of celebration with important others, as diminishing familiar patterns expand moments of respite, while regard from others affirms self, and changing customs create comfort-discomfort as what-was unfolds into new possibles." Findings were congruent with Parse's theoretical concepts of valuing, enabling-limiting, and transforming. This study supported Parse's theory as a valuable guide for human inquiry and expanded the body of nursing knowledge on aging. Specific guidelines for practice and research are proposed. PMID- 1454278 TI - Nursing theory: the 21st century. AB - On September 21, 1990, at the University of California, Los Angeles, Neuropsychiatric Institute and Hospital, six nurse theorists participated in a panel discussion on theory development for the 21st century. The theorists included Dorothy Johnson, Betty Neuman, Dorothea E. Orem, Rosemarie Rizzo Parse, Martha E. Rogers and Callista Roy. The panel provided the participants the opportunity to speculate on the course for future development of nursing knowledge. Three questions were posed to the panel relating to the development of their models, the direction nursing theory will take in the 21st century, and current research emerging from the extant theories. The panel also addressed questions from the audience. PMID- 1454279 TI - Elements of transcultural and translinguistic research: a personal experience. AB - Prior to undertaking the exploration of phenomena in a research study with people from different cultures, certain elements must be addressed in order to bridge cultural and linguistic differences. In this article, the authors explore some of these elements, with specific reference to personal experiences in a research study done in Italy, the results of which will not be presented here. Elements discussed include: transcultural/translinguistic literature review, protection of human subjects, translinguistics, maintaining necessary and appropriate contact with persons at the research site, presentation of research to participants, structuring interviews, and post-session amenities. PMID- 1454280 TI - DSSNY prepares to celebrate children's dental health month. PMID- 1454281 TI - DSSNY makes case against utilization letters. PMID- 1454282 TI - The TMPDS personality: fact or fiction? An overview. AB - It is widely accepted that abnormal personality traits and psychological stress are important factors in the etiology and maintenance of the temporomandibular pain and dysfunction syndrome (TMPDS). However, this assumption is based largely on clinical lore rather than research evidence. Continued belief in the stress theory has onerous implications. Such conclusions will lead not only to problems of patient care, but may also forge an unstable foundation for future research. Three theories have been advanced that support a relationship between personality and TMPDS. They are the psychosomatic, coping and psychophysiological theories. But evidence in support of all three theories is currently lacking. It has not been shown that TMPDS cases are characterized by a specific premorbid personality or an exaggerated vulnerability to psychological stress. PMID- 1454283 TI - Geographic tongue. A case report. PMID- 1454284 TI - Minor salivary gland sialolithiasis. Review and case report. PMID- 1454285 TI - Conservative partial maxillectomy for large odontogenic keratocyst. PMID- 1454286 TI - Columbia School of Dental and Oral Surgery. A 75-year influence on dental education. PMID- 1454287 TI - Iconodontalgia. PMID- 1454288 TI - No more discounts. PMID- 1454289 TI - Relapse! Predictable, preventable and salvageable. PMID- 1454291 TI - [The development of diploid parthenogenetic mouse embryos of the inbred C57BL and CBA strains]. AB - We studied preimplantation development in vitro and postimplantation development in vivo of diploid parthenogenetic mouse embryos of C57BL/6 and CBA strains, as well as of (CBA x C57BL/6)F1 hybrids. Development to blastocyst stage of diploid eggs obtained from C57BL/6, CBA, and hybrid mice was observed in 90, 15, and 73% cases, respectively. After implantation, C57BL/6 embryos did not develop to somite stages, while CBA and hybrid embryos reached various stages of somite formation in 45 and 30% cases, respectively. Cultivation of embryos beginning from one-cell stage in the medium containing 2% newborn calf serum increased the yield of blastocysts from 15 to 59% in CBA embryos and from 73 to 90% in hybrids; However, such effect was not observed with C57BL/6 embryos. The latest stages of development observed in CBA and hybrid diploid parthenogenetic embryos were 33-35 somites and 25-30 somites, respectively. Imprinting patterns in chromosomes of CBA and C57BL/6 gametes are discussed. PMID- 1454290 TI - [The "major" proteins of the human myocardium in ontogeny]. AB - Two-dimensional electrophoresis according to O'Farrell was used for studying changes in the content of major proteins of human myocardium at various stages of pre- and postnatal development. On the basis of the protein pattern specific of certain stages of myocardium differentiation the degree of development of the human cardiac muscle can be determined. The most pronounced changes in myocardium protein spectra are characteristic of the first half of pregnancy. PMID- 1454293 TI - [The testosterone level in the testes of silver foxes during prenatal development]. AB - The level of testosterone in serum and testes of the silver fox fetuses on days 31, 35, 40, 45, and 50 of gestation was determined using radioimmunoassay. In testes, testosterone was first detected at day 31; then its level gradually increased. Serum testosterone was detected only at day 40. Subsequent increase in its concentration was insignificant. Human chorionic gonadotropin stimulated testicular testosterone production in vitro beginning from day 40. We suggest that in the silver fox, testes are capable of responding to gonadotropins already by the day 40 of prenatal development but the formation of pituitary-gonadal axis proceeds until the end of embryogenesis. PMID- 1454292 TI - [The assessment of the level of genetic damages accumulated with age and induced in liver cells by the micronucleus production]. AB - Latent genetic disturbances in aging liver cells can be registered during interphase by the appearance of micronuclei resulting from certain chromosomal aberrations. Micronuclei were also detected in postmitotic hepatocytes of mouse liver regenerating after partial resection of CCl4 poisoning. In 1.5- and 2-month old mice, the proportion of micronuclei-containing cells was on average 0.59 and 0.89%, respectively. At the age of 4 and 7 months, the proportion of aberrant cells in hepatocyte population, including cells containing multiple micronuclei, increased to 5.93 and 11.7%, respectively. In order to evaluate parameters used to characterize "spontaneous" aging, experiments were performed in which genetic disturbances were induced by x-irradiation or treatment with dipin, an alkylating agent (individually or in combination); the effect was determined one and two months after the treatment. The yield of micronuclei under the conditions of a mild treatment (irradiation at a dose of 0.7 and 1.4 Gr or dipin at a dose of 30 mg/kg body weight) was similar to that observed during aging. The possible reasons for the increased (as compared to the published data) rate of genetic disturbances in arbitrary intact animals are discussed. PMID- 1454294 TI - [The distribution and relation to the cytoskeleton of specific prosomal proteins in the oogenesis of the clawed toad]. AB - Using immunoblotting and immunofluorescent microscopy, we showed the presence in Xenopus laevis oocytes of two prosomal proteins (27 and 31-33 kDa) and studied their distribution during oogenesis. In the ooplasm, both proteins are detected in prosomal clusters of various size. During previtellogenesis, prosomal proteins are diffusely distributed in the nucleoplasm and form evenly distributed clusters in the cytoplasm. During oocyte growth, prosomal proteins disappear from the nucleus and form animal-vegetal and cortical gradients in the cytoplasm. In the course of oocyte maturation prosomal clusters become smaller. After artificial activation of the egg, the dorso-ventral gradient of distribution of prosomal proteins is observed. Double immunohistochemical labeling revealed morphological association between prosomal clusters and fibril-like structures of the oocyte containing actin and myosin. The latter are then replaced by diffusely distributed actin and myosin. Thus, correlation is observed between localization of the acto-myosin complex of the oocyte and that of prosomal proteins. PMID- 1454295 TI - [The gametotoxic effect of antenatal exposure to thiotepa in mice]. AB - ThioTEPA was injected intraperitoneally into female 101/H and CBA mice on day 12 of pregnancy at a dose of 2.5 mg/kg body weight. As a result, the number of prospermatogonia in 19-day-old male fetuses decreased to 78.8% in 101/H mice and to 63.7% in CBA mice. The gametotoxic effect on the male offspring (F1) in 101/H mice treated with thioTEPH included the significant decrease in the number of spermatogonia A, spermatocytes I at preleptotene and pachytene, as well as of spermatids at the stage 7 of development. Interstrain differences are described in the intensity of spermatogenesis in the mature intact animals and in regeneration capacity of gonads after prenatal thioTEPA administration. PMID- 1454297 TI - [The centriolar cycle in polykaryons formed in the fusion of heterophasic cells]. AB - In this work we studied the centriolar cycle in fused cells containing heterophasic nuclei. Embryonic pig kidney cells were double-labeled with 3H- and 14C-thymidine and fused using a PEG-DMSO-serum method (Manandkhar et al., 1991). Fused cells containing nuclei at various cell cycle periods were selected after embedding in epon on the basis of isotope marking. Ultrastructure of centrioles was studied in serial ultrathin sections of selected cells. Centrioles of cells fused at different interphase periods showed a tendency to become synchronized in a manner similar to that of the nuclei. The G1-cell partners suppressed replication of S-centrioles or induced disorientation of centrioles of G2 diplosomes. In G1-S fused dikaryons, procentriole formation in G1-centrioles was not observed. This indicates the absence in the S-cell partner of an excess of a factor which could induce replication of the G1-centriole. However, G2-cell partner stimulated procentriole formation in G1- or unreplicated early S centrioles. Asynchronous replication of G1-, S- and G2- centrioles was observed in some G1-S, G1-G2 and S-G2 fused cells. Heterophasic cellular environment containing mixed cell cycle factors appears to be responsible for the opposite effects on the structure of centrioles. In oocytes or early embryonic cells, due to the presence of a large amount of centriolar precursor material, centriolar replication cycle can proceed independently of the synthetic activity controlled by the nucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454296 TI - [The formation of oval-cell ducts during hepatic carcinogenesis in mice. Its relationship to the pre-existing canals of Hering]. AB - It has been shown that a population of the oval cells is formed in mouse liver during the dipin-induced carcinogenesis (Radaeva, Factor, 1990b). This paper deals with the origin of the oval cells and their proliferation potential depending on localization in the liver lobule. Series of semithin liver sections were studied under the light microscope and detected labeled cells analyzed under electron microscope on serial ultrathin sections. We found that proliferation of cells of terminal bile ductules (Hering [correction of Gering] canals) takes place at the early stages of liver carcinogenesis. These cells and first labeled oval cells had similar size and morphology and jointly formed the ducts. Oval cell population was heterogeneous in terms of proliferative potential. Proportion of proliferating cells (38-45%) in the oval cells of Hering [correction of Gering] canals and small ducts surrounding portal tracts remained similar throughout the period of formation of the oval cell population. In the oval cells infiltrating the parenchyma, the proportion of proliferating cells appeared to depend on the intensity of the oval cell response: it attained the maximum (62%) on intermediate stage and decreased to the minimum (22%) at the peak of the reaction. These data suggest that Hering [correction of Gering] canals probably give origin to the ducts formed by oval cells. PMID- 1454298 TI - [A phenogenetic analysis of independent and dependent differentiation]. PMID- 1454299 TI - A corneal topography algorithm that produces continuous curvature. AB - A new method is developed for calculating corneal curvature based on the reflected image of a series of concentric rings (keratoscopy). Previous methods had the drawback that the calculated corneal power was discontinuous in that it changed abruptly at each ring. The present method fits the corneal curvature with a cubic polynomial and produces a continuous estimate of the local power of the cornea. The cubic function also provides a better fit to the corneal curvature than previous methods that used a circle to provide the local fit. The full computer program for the algorithm is presented. Four different definitions of the local dioptric power are discussed. PMID- 1454300 TI - Testing hypotheses on dioptric power. AB - Transformation of dioptric power from the conventional clinical representation as sphere, cylinder, and axis to the vectorial representation known as the vector h makes it possible to apply formal multivariate statistical methods to dioptric power. Methods are described for testing hypotheses on mean dioptric power and on variance-covariance of dioptric power for one and more than one population. A number of numerical examples are presented. Attention is drawn to the underlying assumption of multivariate normality, to other limitations of the methods, and to pitfalls in the use of the methods. Three-dimensional scatter plots, shown by means of stereo-pair drawings, are useful for detecting departures from normality. PMID- 1454301 TI - Quantitative evaluation of the effects of a bicarbonate and glucose-free balanced salt solution on rabbit corneal endothelium in vitro. AB - Whole corneas from 2- to 2.5-kg albino rabbits were perfused in vitro at 35 to 36 degrees C with a commercial balanced salt solution (BSS) that lacks bicarbonate and glucose. The corneas swelled at an average rate of 45 +/- 11 microns/h. Evaluation of the corneal endothelium by scanning electron microscopy revealed no obvious cytotoxic effect beyond the occasional small area affected by air bubble damage. Morphometric analysis of the central corneal endothelium revealed no significant differences between the endothelial mosaic of perfused corneas, when compared to freshly fixed corneas, in terms of percentage 6-sided cells (pleomorphism) and variance in cell areas (polymegethism). In this example, therefore, a corneal swelling induced by a bicarbonate and glucose-free BSS does not appear to be due to either obvious endothelial cytotoxic effects or significant morphological alteration of the endothelial mosaic. PMID- 1454302 TI - Interest of presbyopes in contact lens correction and their success with monovision. AB - The presbyopic population is seen as a large potential source of contact lens wearers. The aims of this study were: (1) to estimate the percentage of presbyopes interested in contact lenses, (2) to ascertain the success of interested presbyopes with monovision correction, and (3) to determine the percentage willing to continue wearing monovision lenses after 1 month's trial. Seven practitioners in Sydney surveyed consecutive presbyopes attending their practices about their interest in contact lenses. Of the 1133 presbyopes surveyed, 314 (28%) were interested in trying monovision lenses. A total of 72 patients were subsequently fitted with monovision in high water content hydrogel form. After 1 month, 46 of these patients (64%) were still wearing the lenses, and 39 (54%) expressed willingness to continue with monovision correction. The major reasons for discontinuation from lens wear during the 1-month trial were inadequate vision and difficulty in lens handling. PMID- 1454303 TI - Crystalline lens power in myopia. AB - Growth of the eye shows a coordinated pattern whereby the reduction in refractive power of the cornea and crystalline lens tends to reduce the myopia that would otherwise result from the normal increase in axial length. There is some controversy as to whether the reduction in crystalline lens power is influenced by the refractive state of the eye, i.e., an active role in the emmetropization process, or is simply related to the changing lens dimension occurring with growth. We measured ocular dimensions and determined the crystalline lens powers in 19 myopes and 19 emmetropic subjects matched for age, gender, and ethnic origin. No significant difference was found in corneal radius of curvature for the two groups, but there was a significant difference (p < 0.05) in crystalline lens power of 2.30 D. These results suggest that greater compensation for axial elongation of the eye was afforded by the decrease in crystalline lens power than by corneal flattening. PMID- 1454304 TI - Anisometropic amblyopia: is the patient ever too old to treat? AB - Amblyopia is an example of abnormal visual development that is clinically defined as a reduction of best corrected Snellen acuity to less than 6/9 (20/30) in one eye or a two-line difference between the two eyes, with no visible signs of eye disease. We describe a sequential management program for anisometropic amblyopia that consists of four steps: (1) the full refractive correction, (2) added lenses or prism when needed to improve alignment of the visual axes, (3) 2 to 5 h/day of direct occlusion, and (4) active vision therapy to develop monocular acuity and improve binocular visual function. We examined records of 19 patients over 6 years of age who had been treated using this sequential management philosophy. After 15.2 (+/- 7.7) weeks of treatment the Amblyopia Success Index (ASI) documented an average improvement in visual acuity of 92.1% +/- 8.1 with a range from a low of 75% by a 49-year-old patient to a maximum of 100% achieved by 42.1% of the patients (8 of 19). Patients who had completed therapy 1 or more years ago (N = 4) maintained their acuity improvement. From these results we conclude that following a sequential management plan for treatment of anisometropic amblyopia can yield substantial long-lasting improvement in visual acuity and binocular function for patients of any age. PMID- 1454305 TI - Reliability of the tear break-up time technique of assessing tear stability and the locations of the tear break-up in Hong Kong Chinese. AB - The measurement of tear break-up time (TBUT) in assessing stability of the tear film is somewhat controversial, even though the technique is widely used. We examined reliability of the technique within and among examiners and conclude that measurements of TBUT can be made reliably; full-beam observation of the cornea is preferable to scanning the cornea with a narrow slit in making the measurements. There may be differences in TBUT measurements made in the same subjects among examiners, but these differences are smaller with more experienced practitioners. In the Hong Kong Chinese (HK-Chinese), tear break-up appears to be more likely to first occur in the inferior periphery of the cornea. In this population mean TBUT is about 7.20 s; assuming a Gaussian distribution of TBUT values, 2.1 s should be adopted as the lower limit for normal TBUT in HK-Chinese. PMID- 1454306 TI - Epidemiological evidence that access to routine optometric care benefits nursing home residents. AB - Public perception is that nursing home residents receive less than adequate health care. To confirm or refute this view we provided routine optometric services to 47 residents in a nursing home who had ready access to primary medical care. Average refractive error, intraocular pressure, visual acuity, and the prevalence of ocular disease were analyzed. Despite the fact that routine primary medical care was provided in-house and ophthalmologic care was provided on a consultation basis, our study revealed a need for further medical intervention. Seven percent of the patients received a legend prescription for drugs for ocular conditions, whereas 11% received an over-the-counter preparation. Although 11% were already under ophthalmological care, we requested consults from ophthalmology for another 11%. An additional patient was referred to an internist. This study shows that even in nursing homes where residents have access to in-house medical management, routine vision care provided by optometrists can disclose undetected medical problems and improve the quality of life. PMID- 1454307 TI - Light-induced amaurosis associated with carotid occlusive disease. AB - A 74-year-old man with the isolated complaint of uniocular transient visual loss after exposure to bright light was found to have severe ipsilateral, atherosclerotic carotid occlusive disease. Signs of ocular ischemia that were present included slightly reduced visual acuity, mild afferent pupillary defect, lowered intraocular pressure, increased photostress recovery time, and reduced opthalmodynamometry values on the affected side. After a subclavian to internal carotid artery bypass procedure, the patient's symptoms resolved completely and his ocular signs returned to normal. This patient's initial symptom, referred to as light-induced amaurosis (LIA), is an unfamiliar manifestation of the ocular ischemic syndrome. We discuss the condition and summarize the literature. PMID- 1454308 TI - Literature review of hepatitis B: should eye care practitioners receive a hepatitis B vaccine? AB - The incidence of Hepatitis B infection has been steadily increasing over the last 5 years. The current literature has established that eye care practitioners are in the high risk category for contracting and transmitting this serious viral infection. Hepatitis B Virus (HBV) is present in all bodily fluids including tears and is considered to be more easily transmitted with a higher degree of infectiousness than Human Immunodeficiency Virus (HIV). Fortunately, unlike Acquired Immune Deficiency Syndrome (AIDS), hepatitis can be prevented with a vaccine. Recent improvements in the hepatitis vaccine have made it safer and more effective. As optometrists expand their scope of practice, it becomes essential to increase the knowledge base and awareness of this clinical entity so informed decisions can be made regarding vaccination by eye care practitioners, teaching faculty, and students. PMID- 1454309 TI - Estimation of dioptric power from measurements that may include measurements of dioptric power. AB - A general routine exists for estimating dioptric power from any number of measurements of sagitta, lens thickness, meridional curvature or power, and prismatic effect. This paper shows how the routine is modified when among the measurements there are measurements of dioptric power itself. PMID- 1454310 TI - More on the future of optometric education. PMID- 1454311 TI - IV steroids for central retinal artery occlusion in giant-cell arteritis. PMID- 1454312 TI - A new image for residency education. PMID- 1454313 TI - National outcomes of cataract extraction. Increased risk of retinal complications associated with Nd:YAG laser capsulotomy. The Cataract Patient Outcomes Research Team. AB - PURPOSE: The authors studied 57,103 randomly selected Medicare beneficiaries who underwent extracapsular cataract extraction in 1986 or 1987 to determine the possible association between performance of neodymium (Nd):YAG laser capsulotomy and the risk of subsequent retinal break or detachment. METHODS: Cases of cataract surgery were identified from Medicare claims submitted in 1986 and 1987 and were followed through the end of 1988. Episodes of cataract surgery, posterior capsulotomy, and retinal complications were ascertained based on procedure and diagnosis codes listed in physician bills and hospital discharge records. Lifetable and Cox's proportional hazards models were used to analyze the risk of retinal detachment or break in patients undergoing and not undergoing capsulotomy during the period of observation. RESULTS: Of the 57,103 persons identified as having undergone extracapsular cataract extraction in 1986 or 1987, 13,709 subsequently underwent Nd:YAG laser capsulotomy between 1986 and 1988. A total of 337 persons had aphakic or pseudophakic retinal detachments between 1986 and 1988 and an additional 194 underwent repair of a retinal break. Proportional hazards modeling shows a 3.9-fold increase in the risk of retinal break or detachment among those who underwent capsulotomy (95% confidence interval: 2.89 to 5.25). Younger patient age, male sex, and white race also were associated with increased risk of retinal complications after extracapsular cataract extraction. CONCLUSION: The authors conclude that there is a statistically significant increase in the risk of retinal detachment or break in those patients who undergo capsulotomy after cataract extraction. Therefore, capsulotomy should be deferred until the patient's impairment caused by capsular opacification warrants the increased risk of retinal complications associated with performance of capsulotomy. PMID- 1454314 TI - Prevalence of glaucoma. The Beaver Dam Eye Study. AB - PURPOSE: The purpose of this study is to determine the prevalence of glaucoma in the population participating in the Beaver Dam Eye Study (n = 4926). METHODS: All subjects were examined according to standard protocols, which included applanation tonometry, examination of the anterior chamber, perimetry, grading of fundus photographs of the optic disc, and a medical history interview. Visual field, cup-to-disc ratio, and intraocular pressure (IOP) criteria were used to define the presence of open-angle glaucoma. Definite open-angle glaucoma was defined by the presence of any two or all three of the following: abnormal visual field, large or asymmetric cup-to-disc ratio, high IOP. RESULTS: The overall prevalence of definite open-angle glaucoma was 2.1%. The prevalence increased with age from 0.9% in people 43 to 54 years of age to 4.7% in people 75 years of age or older. There was no significant effect of sex after adjusting for age. Of the 104 cases of definite open-angle glaucoma, 33 had IOPs less than 22 mmHg in the involved eye. Hemorrhage on the optic disc was found in 46 people; 2 of these had glaucoma. Narrow-angle glaucoma was rare, with two definite cases in the population. CONCLUSION: The prevalence of open-angle glaucoma in Beaver Dam is similar to that in other white populations. Findings from this study re-emphasize the notion that estimates of glaucoma prevalence should be based on assessing multiple risk indicators. PMID- 1454315 TI - Effect of timolol versus pilocarpine on visual field progression in patients with primary open-angle glaucoma. AB - BACKGROUND: Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long term effect of two ocular hypotensive agents on preservation of visual field. METHODS: In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32. RESULTS: Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily. CONCLUSION: Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine. PMID- 1454316 TI - Which is better? One or two? A randomized clinical trial of single-plate versus double-plate Molteno implantation for glaucomas in aphakia and pseudophakia. AB - PURPOSE: Previous studies have suggested that primary double-plate Molteno implantation may be beneficial. Therefore, the authors performed a randomized clinical trial to evaluate the relative effectiveness and safety of single- versus double-plate Molteno implantation. METHODS: From March 1988 to February 1990, 132 patients who underwent Molteno implantation for medically uncontrollable non-neovascular glaucomas in aphakia or pseudophakia were randomly assigned to receive either single- or double-plate implants. RESULTS: The 1- and 2-year life-table success rates (success [survival] defined as 6 mmHg < or = final intraocular pressure [IOP] < or = 21 mmHg without additional glaucoma surgery or devastating complication) were 55% and 46% with single-plate implantation and 86% and 71% with double-plate implantation, respectively. The final postoperative visual acuities were within one line of the preoperative visual acuities or had improved in 73% and 80% of patients, respectively. Choroidal hemorrhages and/or effusions, corneal decompensation, flat anterior chambers, and phthisis bulbi were more common in the patients who had undergone double-plate Molteno implantation; however, transient elevations of IOP during the first few postoperative months were more common in the patients who had undergone single-plate Molteno implantation. CONCLUSIONS: Double-plate Molteno implantation more frequently affords IOP control than single-plate Molteno implantation; however, double plates are associated with greater risks of choroidal hemorrhages and/or effusions, corneal decompensation, flat anterior chambers, and phthisis bulbi. PMID- 1454317 TI - Incidence and management of glaucoma after intravitreal silicone oil injection for complicated retinal detachments. AB - BACKGROUND: Intravitreal silicone oil injection used for managing complicated retinal detachments can be associated with elevated intraocular pressure (IOP). This study was undertaken to determine the incidence of glaucoma in patients who underwent silicone oil injection, as well as to evaluate the effectiveness of medical and surgical therapy in patients in whom glaucoma developed. METHODS: The postoperative courses of 50 eyes of 47 consecutive patients who underwent pars plana vitrectomy and silicone oil injection for the management of complicated retinal detachments were reviewed retrospectively. The outcomes of patients who underwent silicone oil removal and/or glaucoma surgery also were evaluated. RESULTS: The mean overall postoperative IOP before any glaucoma surgery was 16.7 +/- 9.3 mmHg (range, 0 to 45 mmHg), with a mean follow-up of 16.6 +/- 12.1 months (range, 2 to 51 months). Twenty-four (48%) eyes had postoperative IOPs of at least 25 mmHg and IOP elevations of at least 10 mmHg above the preoperative levels. Twenty-one (42%) eyes underwent complete removal of silicone oil and/or glaucoma surgery to effect IOP control. The IOPs were controlled to 21 mmHg or less (but > 5 mmHg) in 8 of 14 eyes that underwent removal of silicone oil alone, in 3 of 5 eyes that underwent Molteno implantation, and in 1 eye that underwent Nd:YAG transscleral cyclophotocoagulation, but not in 1 eye that underwent a modified Schocket procedure (mean follow-up, 13.5 +/- 11.0 months; range, 0.2 to 33 months). CONCLUSION: Intraocular pressure elevation is a common occurrence after intravitreal silicone oil injection. The underlying mechanism may often be multifactorial in nature. Patients in whom uncontrolled IOP develops may benefit from aggressive medical and/or surgical treatment with silicone oil removal, glaucoma implants, or cyclodestructive procedures. PMID- 1454318 TI - Diabetes, hyperglycemia, and age-related maculopathy. The Beaver Dam Eye Study. AB - PURPOSE: The purpose of this study is to examine the association among hyperglycemia, diabetes status, and age-related maculopathy in a population-based study of people between the ages of 43 and 86 years who lived in Beaver Dam, Wisconsin between 1988 and 1990. METHODS: Age-related maculopathy was determined from stereoscopic fundus photographs. RESULTS: In the nondiabetic group (n = 4291), no relationship was found between glycosylated hemoglobin and any signs of age-related maculopathy. Diabetes status was not associated with early age related maculopathy. People 75 years of age or older with diabetes (n = 85) had a higher frequency of exudative macular degeneration (9.4%) than those without (4.7%) but had similar frequencies of pure geographic atrophy (3.8% for those with diabetes and 3.4% for those without diabetes). The relative risk of exudative macular degeneration in men with diabetes who were 75 years of age or older compared with those who did not have diabetes was 10.2 (95% confidence interval [CI]: 2.4, 43.7); for females it was 1.1 (95% CI: 0.4, 3.0). CONCLUSION: These data suggest that diabetes is not related to early age-related maculopathy or geographic atrophy. The relationship of exudative macular degeneration to diabetes in older men, but not women, may be a result of chance. Further longitudinal study of this observation is needed. PMID- 1454319 TI - Pars plana vitrectomy for intraocular inflammation-related cystoid macular edema unresponsive to corticosteroids. A preliminary study. AB - PURPOSE: To determine the role of pars plana vitrectomy in patients with intraocular inflammation-related cystoid macular edema that is unresponsive to corticosteroids. METHODS: Eleven eyes of nine patients underwent a standard three port pars plana vitrectomy. The primary indication was intraocular inflammation related cystoid macular edema that was unresponsive to oral, sub-Tenon's, and topical corticosteroids. Preoperative follow-up ranged from 20 months to 144 months (average, 70 months). Postoperative follow-up ranged from 3 months to 108 months (average, 21 months). RESULTS: Seven eyes (64%) improved 4 or more lines of Snellen visual acuity within 4 weeks. Two eyes (18%) remained unchanged and 2 eyes (18%) worsened. Cystoid macular edema improved by clinical examination and fluorescein angiography in 9 eyes (82%) and by clinical examination alone in 2 eyes (18%). No intraoperative complications were noted. Postoperative complications consisted of cataract formation in 1 eye (9%), glaucoma in 2 eyes (18%), and epiretinal membrane formation in 1 eye (9%). CONCLUSION: Pars plana vitrectomy may have a role in the treatment of intraocular inflammation-related cystoid macular edema that fails to respond to corticosteroids. The subgroup of patients who benefit most remains to be identified. PMID- 1454320 TI - Use of perfluoroperhydrophenanthrene in the management of suprachoroidal hemorrhages. AB - BACKGROUND: Suprachoroidal hemorrhage may cause the expulsion of intraocular contents. Generally, cases of nonexpulsive suprachoroidal hemorrhage have a better outcome than their expulsive counterparts. Those cases with massive nonexpulsive suprachoroidal hemorrhage do better with treatment than without. Treatment modalities have included suprachoroidal hemorrhage drainage with or without intraocular volume reformation, and vitrectomy. METHODS: The authors used the liquid perfluorocarbon perfluoroperhydrophenanthrene in the treatment of three patients with nonexpulsive suprachoroidal hemorrhage. The perfluorocarbon was injected into the vitreous cavity while the suprachoroidal blood was drained through anterior sclerotomies. RESULTS: With 5 months of follow-up, complete resolution of the suprachoroidal blood was noted in all patients. All three patients had attached retinas, and postoperative visual acuities were improved over preoperative visual acuities. CONCLUSION: Perfluoroperhydrophenanthrene and other perfluorocarbon liquids may be beneficial in the treatment of certain cases of nonexpulsive suprachoroidal hemorrhages. PMID- 1454321 TI - Correlation between biochemical composition and fluorescein binding of deposits in Bruch's membrane. AB - PURPOSE: The fluorescence of drusen during fluorescein angiography is believed to have important prognostic and pathogenetic implications in age-related maculopathy. It is believed that deposits containing predominantly neutral lipids would be hydrophobic, resulting in hypofluorescence on fluorescein angiography, while the presence of polar phospholipids would be indicated clinically by hyperfluorescence because of its hydrophilic properties. To identify the potential determinants of fluorescence of drusen and Bruch's membrane, a series of macular specimens from human donors older than 60 years of age was examined. No clinical information was available concerning any previous eye disease. METHODS: In vitro fluorescein binding was recorded microscopically, and the presence of fibronectin was sought by immunohistochemistry. The results were correlated with the proportions of phospholipids to neutral lipids identified by histochemical and biochemical studies. RESULTS: It was found that high content of neutral fats was associated with lack of both fluorescein binding and fibronectin, and, conversely, in those specimens with high proportions of phospholipids, fluorescein binding was strong and fibronectin was present. CONCLUSIONS: These observations support the central hypothesis concerning biophysical changes in Bruch's membrane with age and the potential importance of fluorescein angiography in the characterization of Bruch's membrane deposits. PMID- 1454322 TI - Comparison of photocoagulation with the argon, krypton, and diode laser indirect ophthalmoscopes in rabbit eyes. AB - PURPOSE: The purpose of this study is to compare photocoagulation with the argon green, krypton red, and diode infrared laser indirect ophthalmoscopes in an experimental setting. METHODS: Photocoagulation was performed with each of the laser indirect ophthalmoscopes in a grid pattern within one sector of the same eye of 14 Dutch-belted rabbits. Treatment was performed either with or without scleral depression. Measurements of the retinal burn diameters were performed after hemisecting the globes, and the burns were examined with light microscopy. RESULTS: Variation in burn intensity and diameter (10% to 28%) was common with all 3 laser indirect ophthalmoscopes. Five times more output energy was required to make equivalent burns with the diode laser indirect ophthalmoscope than with the argon or krypton laser indirect ophthalmoscopes. Choriovitreal hemorrhages only occurred during scleral depression. Histopathologically, the argon green laser indirect ophthalmoscope burns spared the choroid and inner sclera, while the intense krypton and diode burns had full-thickness choroidal involvement and even thermal injury to the inner sclera. Scleral depression reduced the mean energy required to create equivalent burns with all three laser indirect ophthalmoscopes. There was a 10% to 40% reduction in the mean retinal burn diameter with scleral depression (argon green, P < 0.0005; krypton red, P < 0.0005; and diode, P < 0.025). CONCLUSION: Photocoagulation with the argon green, krypton red, or diode infrared laser indirect ophthalmoscopes is a safe and effective method of retinal ablation. Decreasing the posterior nodal distance of the eye with scleral depression will produce a smaller spot on the retina with the laser indirect ophthalmoscope. PMID- 1454323 TI - Avellino corneal dystrophy. Clinical manifestations and natural history. AB - PURPOSE: The pathologic features of a variant of granular corneal dystrophy has been described in which the presence of lattice changes in addition to characteristic granular lesions has been documented. The authors investigated the mode of inheritance, natural history, and clinical manifestations of this dystrophy. METHODS: A family with this condition was investigated, and a pedigree was established. Family members underwent ophthalmic examination, and ophthalmic history was obtained. In addition, pathologic examination of corneal tissue from affected patients was performed. RESULTS: Similar to the four previously described cases, this family also traced its origins to Avellino, Italy. This autosomal dominant condition affected 27 of 92 family members, ranging in age from 5 to 77 years. Granular deposits were the earliest and most common manifestations. Lattice lesions were present in some patients with granular lesions. Older patients had anterior stromal haze between deposits, which impaired visual acuity. Recurrent granular deposits were noted in donor corneal tissue after penetrating keratoplasty for this condition. Pathologic examination of corneal tissue from affected patients confirmed the presence of hyaline material seen in granular dystrophy as well as fusiform deposits of amyloid, similar to those seen in lattice dystrophy type I. CONCLUSION: This study establishes the natural history and clinical manifestations of this condition. PMID- 1454324 TI - Effects of povidone-iodine chemical preparation and saline irrigation on the perilimbal flora. AB - PURPOSE: To analyze the effects of 5% povidone-iodine preparation and saline irrigation on the species composition of perilimbal flora. METHODS: Cultures were taken from the perilimbal conjunctiva in 100 eyes before preparation for ophthalmic surgery, after instillation of povidone-iodine solution, and after saline irrigation. RESULTS: Bacteria were isolated in 75% of eyes before preparation, in 28% after povidone-iodine instillation, and in 24% after saline irrigation. Fifty-one culture-positive eyes became negative with povidone-iodine, while only four culture-negative eyes became culture-positive (P < 0.001). The number of eyes yielding coagulase-negative staphylococci, Staphylococcus aureus, and Propionibacterium were significantly decreased after povidone-iodine instillation. Twenty-three culture-positive eyes became negative after saline irrigation, while 19 culture-negative eyes became culture-positive (P > 0.25). CONCLUSION: Povidone-iodine solution is effective in reducing bacterial recovery from the perilimbal conjunctiva, where most incisions for intraocular surgery occur. Saline irrigation after povidone-iodine preparation has no significant effect. PMID- 1454325 TI - Wolfring dacryops. AB - BACKGROUND: A unique series of 13 cases of ductal cysts of the accessory lacrimal glands of Wolfring is presented. Once appreciated, they are an easily recognized clinical entity. METHODS: The 13 cases were verified histologically as arising from ductal epithelium. Biochemical analyses for serum and cyst fluid concentrations of IgA, IgG, and IgM were performed on three of the cases. Histologic staining of the cyst wall using monoclonal antibodies to immunoglobulins was performed on one case. FINDINGS: All patients had evidence of extensive trachomatous scarring. High levels of IgA were found in the cyst fluid, consistent with an active secretory mechanism. Monoclonal antibody staining suggested a significant role for paraductal IgA-secreting plasma cells. CONCLUSION: The formation of a ductal cyst appears to require two successive, inter-related events. The first is an ongoing active secretory process, and the second is an occlusion of the duct. The sequential occurrence of these two events is forwarded as the explanation of dacryops formation. Excision using a conjunctival approach is recommended. A small strip of tarsal border should be removed with the cyst to prevent cyst rupture. The excretory ducts of the Wolfring glands exit through this area. PMID- 1454326 TI - Malignant lymphoma of the ocular adnexa associated with the benign lymphoepithelial lesion of the parotid glands. Report of two cases. AB - BACKGROUND: The benign lymphoepithelial lesion of the salivary/lacrimal glands is generally regarded as a lymphoproliferative disorder that may be associated with Sjogren syndrome. Although lymphomatous transformation in patients with Sjogren syndrome is well documented, few reports have appeared describing similar findings in patients with a benign lymphoepithelial lesion. METHODS: The authors report the unusual occurrence of malignant lymphoma involving the ocular adnexa in two patients with a histopathologically documented benign lymphoepithelial lesion of the parotid glands. RESULTS: Both patients developed B-cell lymphomas. The eyelid tumor in case 1 expressed IgM/kappa cell surface markers by flow cytometry, and the orbital/conjunctival masses in case 2 showed neoplastic nodules of B cells that were only immunoreactive to lambda light chains (avidin biotin complex method). CONCLUSION: To the authors' knowledge, this is the first report of ocular adnexal lymphoma arising in patients with a benign lymphoepithelial lesion of the parotid glands. This report establishes that ocular adnexal lymphoma may arise in a patient with a preexisting benign lymphoepithelial lesion. PMID- 1454327 TI - Orbital lymphangioma. Correlation of magnetic resonance images and intraoperative findings. AB - BACKGROUND: Orbital lymphangiomas generally are invasive, slow-growing lesions that can produce proptosis, motility impairment, and compressive optic neuropathy. Successful surgical management requires detailed preoperative radiologic imaging with the capacity to determine the location and size of the tumors, the presence of cystic or solid components, and extent of infiltration of the tumor into normal orbital structures. METHODS: The records of 12 patients with orbital lymphangioma were reviewed with attention to the clinical, radiologic, operative, and histologic findings. RESULTS: Preoperative magnetic resonance imaging (MRI) produced highly detailed renderings of the orbital mass that were both diagnostic and predictive of the intraoperative findings. Magnetic resonance imaging was particularly sensitive to the presence of cysts within the tumor and was able to predict the contents of the cysts. CONCLUSION: Using preoperative MRI, a more detailed and accurate surgical plan can be formulated than with any other noninvasive technique. PMID- 1454328 TI - Malignant peripheral nerve sheath tumor of the orbit in a 15-month-old child. Nine-year survival after local excision. AB - BACKGROUND: Malignant peripheral nerve sheath tumors are extremely rare orbital tumors that carry a poor prognosis despite wide excision with disfiguring surgery, chemotherapy, or radiotherapy. The authors present the youngest reported case, a 15-month-old boy who underwent an orbitotomy to excise a bilobed tumor from the right orbit. FINDINGS: Histologic examination revealed a malignant peripheral nerve sheath tumor; standard treatment options, including orbital exenteration, chemotherapy, and radiotherapy, were denied and instead the patient was followed with serial computed tomography scans and magnetic resonance imaging. RESULTS: Nine years later, the patient remains without evidence of recurrent tumor and visual acuity is 20/20. CONCLUSION: This patient's course suggests that orbital malignant peripheral nerve sheath tumors, if believed to be completely excised at the time of surgery, might be followed with careful neuroimaging studies for signs of recurrence. PMID- 1454329 TI - Complications associated with alloplastic implants used in orbital fracture repair. AB - BACKGROUND: The treatment of orbital wall fractures involves observation and/or surgical reduction with repositioning of herniated orbital tissues. To prevent reherniation of tissue and development of enophthalmos, the orbital floor or wall defect is commonly covered with an alloplastic implant. Complications associated with these implants are infrequent and generally appear as isolated case reports. METHODS: The authors reviewed the files of four consultative oculoplastic surgeons and searched for individuals with complications secondary to their alloplastic implants used during orbital fracture repair. FINDINGS: Seventeen patients were identified with a variety of complications related to their alloplastic implant. CONCLUSION: Although these implants are relatively inert and develop a fibrous capsule walling them off from the surrounding orbit, they remain foreign bodies and are thus subject to possible complications at any time. The authors review the spectrum of complications occurring with various alloplastic implants. PMID- 1454330 TI - A new classification of superior oblique palsy based on congenital variations in the tendon. AB - BACKGROUND: Superior oblique palsy is the most frequent isolated cranial nerve palsy seen in strabismus practice. It is traditionally diagnosed according to etiology as acquired, congenital, or idiopathic, but surgical treatment is based on deviation not etiology. Observations at surgery led to speculation that the superior oblique tendon is different in congenital compared with acquired superior oblique palsy and that this difference should be considered in surgical treatment. METHODS: The authors reviewed the charts of 82 patients (89 eyes) undergoing surgery on the superior oblique tendon for superior oblique palsy. In each case, the palsy had been diagnosed preoperatively as acquired, congenital, or idiopathic, and, at surgery, characteristics of the tendon anatomy were described. RESULTS: Thirty-eight superior oblique tendons (36 patients), diagnosed as congenital superior oblique palsy, included 33 abnormal tendons and 5 normal tendons. Twenty-four tendons (21 patients), diagnosed as traumatic superior oblique palsy, included 22 normal and 2 abnormal tendons. Twenty-seven tendons (25 patients), diagnosed as idiopathic, included 19 normal and 8 abnormal tendons. Abnormal tendons were divided into 4 categories: (1) redundant, (2) misdirected, (3) inserted in posterior Tenon's capsule, and (4) absent. CONCLUSIONS: The authors conclude that congenital superior oblique palsy is usually associated with a structural abnormality of the superior oblique tendon (87%). Whereas acquired superior oblique palsy usually has a normal tendon (92%). Superior oblique underaction in acquired superior oblique palsy results from a neural deficit. Potential variance in anatomy of the superior oblique tendon should be considered when undertaking surgery for superior oblique palsy. PMID- 1454331 TI - Results of amblyopia therapy in eyes with unilateral structural abnormalities. AB - PURPOSE: The purpose of this study is to analyze the visual results of full-time occlusion therapy in pediatric patients with monocular structural abnormalities and amblyopia. METHODS: The authors reviewed the charts of visually immature patients with unilateral structural abnormalities and decreased visual acuity, who presented to the University of Iowa Hospitals and Clinics over a 20-year period, and underwent amblyopia therapy. The results were categorized according to the type of structural abnormality (i.e., partial media opacity, macula lesion, or optic nerve abnormality). Associated factors, including anisometropia, strabismus, age of presentation, and pupillary responses, were analyzed. RESULTS: Fifty-one percent of the 51 patients in the study achieved a visual acuity of at least 20/80, including 72% of the patients with media opacities, 42% with macular lesions, and 21% with optic nerve anomalies. Strabismus and anisometropia occurred frequently and were not prognostically significant. Relative afferent pupillary defects did not contraindicate good results. Amblyopia recurred in 31% of patients and was successfully treated with resumption of full-time occlusion. Occlusion amblyopia occurred in only one patient and was easily reversed. CONCLUSION: The authors recommend a trial of full-time occlusion for patients with all three types of unilateral structural abnormalities. The patients with partial media opacities have a high success rate. Despite lower success rates for the other two groups, good results are possible; no better treatment option exists. PMID- 1454332 TI - Visual rehabilitation. The challenge, responsibility, and reward. AB - BACKGROUND: A multispecialty ophthalmology clinic created a not-for-profit foundation to establish a center for visual rehabilitation. METHODS: The Center's objective of equipping and enabling visually impaired people to lead more productive, independent, and satisfying lives by improving their remaining functional sight is performed through a four-phase program comprised of an intake interview, low vision examination, rehabilitation training, and counseling. RESULTS: Since its inception in 1986, the Center has cared for 947 females and 511 males. Although the majority of the patients examined are 61 to 90 years of age, all age groups have received care, including 41 patients younger than 10 years of age and 42 patients 91 years of age or older. CONCLUSION: The role of the ophthalmologist in the visual rehabilitation process is pivotal. The author acknowledges that most practices are unable to develop such a center. A number of suggestions are made, however, that may enable many practices to participate in the rehabilitation of their patients. PMID- 1454333 TI - Laser treatment of corneal vessels. PMID- 1454334 TI - Malignant glaucoma after laser iridotomy. PMID- 1454335 TI - Scleral buckling versus pneumatic retinopexy. PMID- 1454336 TI - Exfoliation material on IOLs. PMID- 1454337 TI - Who should receive mitomycin-C after pterygium surgery? PMID- 1454338 TI - Serious complications of topical mitomycin-C after pterygium surgery. AB - BACKGROUND: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. METHODS: The authors report on a series of 10 patients who experienced serious, vision-threatening complications associated with the use of this drug after pterygium surgery. RESULTS: Complications included severe secondary glaucoma (4 patients), corneal edema (3 patients), corneal perforation (1 patient), corectopia (2 patients), iritis (8 patients), sudden onset mature cataract (2 patients), scleral calcification (1 patient) and incapacitating photophobia and pain (8 patients). Two patients required penetrating keratoplasties and a third required three lamellar keratoplasties. Another patient underwent four additional surgeries including a conjunctival Z-plasty, scleral patch grafting, and conjunctival autografting before his intractable pain and photophobia resolved 15 months after the original surgery. Because of these complications, 6 patients required a total of 20 return visits to the operating room after their original pterygium surgery. In 5 eyes, visual acuity remained at 20/200 or less. Three of the six patients with the most severe complications had concomitant chronic external diseases (rosacea [3 patients], ichthyosis [1 patient], keratitis sicca [1 patient]). CONCLUSION: The authors urge extreme caution in the use of mitomycin. If mitomycin is used, the lowest possible concentration should be applied for the shortest time period in an effort to avoid these complications. A prospective multicenter study of the ophthalmic use of this medication is needed. PMID- 1454339 TI - Sterile endophthalmitis after sutureless cataract surgery. AB - BACKGROUND: Sutureless cataract surgery has recently increased in popularity because of the rapid visual rehabilitation and the inherent reduction of surgically induced astigmatism. METHODS: This procedure is dependent on a lamellar, multiplaned incision. As with new surgical techniques, associated complications become evident with time. Recently, there have been several cases of infectious endophthalmitis after this procedure. The authors report on nine cases of sterile endophthalmitis. In all nine cases, surgery was performed with refrigerated balanced salt solution (BSS) and 100 mg of cefazolin and/or 20 mg of methylprednisolone sodium succinate, given subconjunctivally, at its completion. RESULTS: All nine cases occurred in a period of time during which 68 cases were performed using refrigerated BSS for irrigation. These nine cases came from two different surgeons using basically the same surgical technique. After the investigation of these complications, the refrigerated BSS was discontinued, and there have been no episodes of sterile endophthalmitis in the last 650 cases. CONCLUSION: It appears that refrigerated BSS should be avoided if periocular injections are going to be used. It may be that the cold BSS fails to allow sufficient tissue swelling to seal the surgical incision, allowing for subconjunctival injections to seep into the wound, and leading to a sterile endophthalmitis. PMID- 1454340 TI - Comparison of depth of focus and low-contrast acuities for monofocal versus multifocal intraocular lens patients at 1 year. AB - PURPOSE: Multifocal lenses have been shown to produce enhanced near and intermediate vision. The division of incoming light into more than one focal point must physically produce retinal images of reduced contrast. The purpose of this report is to provide quantitative data on the increased depth of focus and decreased contrast sensitivity demonstrated in patients receiving the 3M diffractive multifocal lens versus the parent monofocal control lens. METHODS: Uncorrected and best-corrected distance and near acuities, Regan and Pelli-Robson contrast sensitivity measurements, and defocus curves were obtained on 22 eyes with monofocal and 16 eyes with multifocal age-matched, pathology-free implants at 1 year after surgery. FINDINGS: Visual acuity data demonstrated significantly improved (P < 0.001) near acuities in multifocal patients with manifest refraction in place. No difference was noted between implants for other acuity measures. A statistically significant reduction (P < 0.05) in contrast sensitivity was measured for multifocal implants at the limits of contrast and resolution (Regan 4%); however, careful patient questioning revealed no clinical impact. Defocus curves demonstrated significantly increased (P < 0.0001) depth of focus at the 20/40 acuity level of 3.8 diopters (D) in multifocal patients versus 1.8 D in monofocal patients. CONCLUSION: The quantifiable and expected loss of contrast sensitivity in the examining lane, not manifest in patient awareness, appears to be an acceptable tradeoff for enhanced near/intermediate vision and depth of focus. PMID- 1454341 TI - Macular pseudoholes. Clinical features and accuracy of diagnosis. AB - BACKGROUND: Epimacular membrane with pseudohole is an important vitreomacular disorder that belongs in the differential diagnosis of impending and established macular hole. To better characterize this lesion, the authors attempted to identify various features of eyes with epimacular membrane and pseudohole. METHODS: Demographic, clinical, photographic, and fluorescein angiographic data for 14 eyes with epimacular membrane and pseudohole were reviewed. Horizontal and vertical diameters of the pseudoholes were measured, and the original diagnosis was recorded for each eye. Fluorescein angiography was performed in 11 eyes. RESULTS: The mean age of patients with macular pseudoholes was 61.6 years, and median visual acuity for pseudohole eyes was 20/30. Mean horizontal and vertical diameters of the pseudoholes were 384 and 410 microns, respectively. None of the eyes with pseudoholes had the characteristic ophthalmoscopic features associated with full-thickness macular holes or impending macular holes. Results of fluorescein angiography showed three eyes with increased tortuosity or abnormal straightening of the perifoveal vessels; three eyes with a foveal window defect; and three eyes with late leakage from the perifoveal vessels. The original diagnosis of the initial examining physician was correct in only 43% of eyes with epimacular membrane and pseudohole. CONCLUSION: Epimacular membrane with pseudohole may be an underdiagnosed lesion and commonly mistaken for impending macular hole, full-thickness hole, or lamellar hole. These data may be of use as more patients are being considered for recently advocated surgical treatments for impending and established macular hole. PMID- 1454342 TI - Retinal pigment epitheliopathy after macular hole surgery. AB - BACKGROUND: Full-thickness idiopathic macular holes were previously considered untreatable, but surgical intervention has been proposed to collapse the hole and improve vision. This study evaluates the fluorescein angiographic changes that occur after macular hole surgery. METHODS: Sixteen patients with stage III idiopathic macular holes underwent pars plana vitrectomy, removal of the posterior hyaloid, peeling of fine epiretinal sheets along the edges of the holes, and fluid-gas exchange. Preoperative fluorescein angiograms were performed, and best-corrected preoperative visual acuity was 20/200 or less in all eyes. RESULTS: Postoperatively, the macular hole disappeared in 12 eyes (75%). In all 12 eyes, retinal pigment epithelial swelling was present, with a unique fluorescein angiographic appearance. This pattern slowly resolved over months, with gradual visual improvement but residual retinal pigment epithelial mottling. Systemic and periocular steroids had no significant impact on the process. CONCLUSION: The combination of prolonged intraocular gas contact and light exposure exceeding threshold for an already compromised macula appears to be responsible for this pigmentary pattern. Depending on the severity of the pigment epithelial alteration, this unique pattern may portend a guarded visual prognosis in affected patients undergoing successful macular hole repair. PMID- 1454343 TI - Detection of drusen and early signs of age-related maculopathy using a nonmydriatic camera and a standard fundus camera. AB - PURPOSE: The study was designed to compare the severity of age-related maculopathy as graded from photographs taken using three different techniques. METHODS: Two methods of nonstereoscopic 45 degrees retinal photography of the macula (through a nonpharmacologically dilated pupil and through a pharmacologically dilated pupil) were compared with results from standard 30 degrees stereoscopic photographs in 112 subjects. Corresponding photographic fields were graded by a masked grader for the presence of any drusen, soft drusen, retinal pigment epithelial degeneration, increased retinal pigmentation, and early and late age-related maculopathy. RESULTS: Exact agreement between gradings of the 45 degrees photographs taken through nonpharmacologically dilated pupils and 30 degrees photographs taken through dilated pupils was 75% for any drusen, 72% for soft drusen, 72% for retinal pigment epithelial degeneration, 74% for increased retinal pigment, 85% for pure geographic atrophy, and 89% for exudative macular degeneration. The kappa scores varied from 0.33 for geographic atrophy to 0.60 for exudative macular degeneration. Slightly higher rates of agreement between gradings were found after dilation. CONCLUSION: These data suggest that 45 degrees nonstereoscopic fundus photographs, when graded according to a standard classification scheme, should be considered for detection of age related maculopathy in situations where the pupils cannot be pharmacologically dilated and retinal specialists are not available to examine the fundus. PMID- 1454344 TI - Scleritis as an initial manifestation of choroidal malignant melanoma. AB - PURPOSE: The purpose of this article is to present the unusual circumstances in which malignant melanoma of the choroid can masquerade as scleritis, thus confounding its diagnosis. METHODS: Three cases of plaque-like malignant melanomas of the choroid are reported that, on initial examination, had features of scleritis. The events leading to their eventual correct diagnosis also are presented. RESULTS: In each case, there was ocular pain, blurred vision, anterior chamber and/or vitreous cavity cellular reaction, and an exudative retinal detachment associated with an ill-defined, relatively flat variably pigmented choroidal mass. In all three cases, the inflammatory component responded promptly to corticosteroid treatment and was accompanied by visual improvement. In two eyes, shrinkage of the choroidal mass accompanied the corticosteroid treatment, lending support to a working diagnosis of scleritis. By demonstrating expansion of the choroidal masses, examination of sequential fundus photographs influenced the decision to enucleate the eyes for presumed malignant choroidal melanoma. CONCLUSION: Clinicians should be alert to the circumstances in which malignant melanomas of the choroid can masquerade as scleritis. Careful evaluation by ophthalmoscopy, ultrasonography, fundus photography, and subsequent sequential examination is necessary to arrive at the correct diagnosis. PMID- 1454345 TI - Natural history of diffuse uveal melanocytic proliferation. Case report. AB - BACKGROUND: Diffuse uveal melanocytic proliferation is a rare paraneoplastic syndrome resulting in rapid bilateral visual loss due to proliferation of benign melanocytes within the choroid and ciliary body. Most of the previously reported cases have been seen with bilateral involvement and typical ocular features. PATIENT: The authors report the case of a 61-year-old man who presented with uniocular posterior pole lesions at the level of the retinal pigment epithelium and subsequently developed the typical bilateral lesions of diffuse uveal melanocytic proliferation. His clinical course was typical, with visual disturbance preceding signs and symptoms of malignancy by 5 months. Rapid decline ensued, and he eventually died 10 months after the onset of visual symptoms. RESULTS: Results of ocular pathologic examination showed the typical choroidal thickening due to the proliferation of melanocytes and the primary tumor was found to be an undifferentiated adenocarcinoma originating in either the pancreas or the esophagus. CONCLUSIONS: The very early funduscopic and fluorescein angiographic findings of diffuse uveal melanocytic proliferation are presented as well as the evolution, ocular pathology, and possible mechanisms for its development. PMID- 1454347 TI - Cellular blue nevus of the conjunctiva. AB - BACKGROUND: Cellular blue nevi of the conjunctiva are extremely rare, and their natural history and malignant potential have not been fully ascertained. METHODS: A report of an unusually well-documented case of growth of a cellular blue nevus is presented, along with a review of current knowledge of this lesion. RESULTS: A 71-year-old woman presented with a darkly pigmented raised lesion of the conjunctiva, which had slowly enlarged over 47 years. There were nonconfluent areas of involvement of the upper and lower lids. Results of biopsy showed the lesion to be a cellular blue nevus, with no evidence of malignancy. CONCLUSION: This well-documented case of slow growth and spread without malignant transformation adds to the knowledge of this rare lesion. PMID- 1454346 TI - Pigmented adenoma of the optic nerve head simulating a melanocytoma. AB - PURPOSE: The purpose of this report is to describe a clinicopathologic correlation of an unusual pigmented tumor of the optic nerve head, to point out that such a lesion can simulate clinically a melanocytoma of the optic disc, and to discuss the differential diagnosis of pigmented epipapillary lesions. FINDINGS: Histopathologic studies of the affected eye showed a peculiar pigmented tumor of the optic disc that was compatible with an adenoma arising from the juxtapapillary retinal pigment epithelium. CONCLUSIONS: Adenoma of the retinal pigment epithelium can closely simulate a melanocytoma of the optic disc. There are some clinical features that may serve to differentiate the two lesions. PMID- 1454348 TI - Retinal findings after head trauma in infants and young children. AB - BACKGROUND: Many authorities believe that the finding of retinal hemorrhages in a child younger than 3 years of age with a history of head trauma, in the absence of an obvious cause for the injury, is pathognomonic of child abuse. To date, no studies have examined the prospective retinal examination of children who have had head trauma. The authors undertook such a study because the presence of retinal hemorrhage from any head trauma in children may have medicolegal diagnostic significance in differentiating accidental from nonaccidental trauma. METHODS: Seventy-nine children younger than 3 years of age, each of whom experienced head injury, underwent an ophthalmologic assessment, which included a dilated funduscopic examination. RESULTS: Seventy-five children sustained accidental head injuries and had normal funduscopic examinations. Three children had nonaccidental head injuries and all were found to have varying degrees of retinal hemorrhages. One child, with a normal fundus examination, had injuries that were of indeterminate cause. CONCLUSION: The finding of retinal hemorrhages in a child with a head injury suggests a nonaccidental cause. PMID- 1454349 TI - Effect of mydriasis on visual field area in retinitis pigmentosa. AB - PURPOSE: The effect of mydriasis on Goldmann visual field area in patients with retinitis pigmentosa has not been suitably defined. The aim of this study is to determine whether visual field area in these patients varies with pharmacologic mydriasis. METHODS: Fifteen adult patients with retinitis pigmentosa were studied prospectively. Goldmann visual fields with II4e and V4e isopters were obtained in both eyes before and after full pharmacologic mydriasis of the right eye. The isopter areas were quantified and analyzed to determine the effect of mydriasis on visual field area. RESULTS: The difference in the right eye isopter areas was compared with the difference in the left eye isopter areas using paired t tests, where the differences were computed from areas obtained before and after dilation of the right eye. Mydriasis had no significant effect on the visual field in terms of isopter area difference (II4e, P = 0.87; V4e, P = 0.45) and percent change in isopter area (II4e, P = 0.81; V4e, P = 0.24). CONCLUSION: Pharmacologic mydriasis had no appreciable effect on the Goldmann visual field area in a selected group of patients with retinitis pigmentosa. These findings suggest that visual fields of such patients obtained in the dilated or undilated state can be meaningfully compared. PMID- 1454350 TI - Augmentation laser for proliferative diabetic retinopathy that fails to respond to initial panretinal photocoagulation. AB - PURPOSE: A study was performed to determine if diabetic subjects who fail to respond to initial panretinal photocoagulation with regression of retinopathy risk factors do better with supplemental panretinal photocoagulation. METHODS: Thirty-five patients with 3 or more retinopathy risk factors who failed to respond to panretinal photocoagulation with regression to less than 3 retinopathy risk factors by 3 weeks after initial panretinal photocoagulation were prospectively randomized to augmentation laser panretinal photocoagulation (MORE) or to no additional treatment (NOMORE). RESULTS: Six months after initial treatment, the MORE group (n = 16) had regressed a mean of -0.94 retinopathy risk factors (with 95% confidence interval [CI] -1.60 to -0.26), compared with -0.21 retinopathy risk factors (95% CI -0.69 to 0.27) in the NOMORE (n = 19) group (P = 0.055). However, by 1 year, there was no statistically significant difference in the amount of regression of retinopathy risk factors with a mean decrease of 1.12 (95% CI -2.0 to -0.24) versus -1.05 retinopathy risk factors (95% CI -1.80 to -0.28) in the 2 groups, respectively. Similarly, for visual acuity, there was no difference in outcome. For all study patients, the persistence of three or more retinopathy risk factors was associated with a poorer visual result than if there was regression to less than three retinopathy risk factors. CONCLUSION: This study shows that although augmentation panretinal photocoagulation achieved faster regression of retinopathy risk factors, by 1 year, there was no difference in either mean regression of retinopathy risk factors or visual acuity between eyes treated or not treated with augmentation panretinal photocoagulation. In addition, the study shows that the persistence of 3 or more retinopathy risk factors 1 year after treatment was associated with a poorer visual result. Because sample size limited the power of the study to find small differences between groups, and because in proliferative diabetic retinopathy small differences could be important clinically, the authors do not recommend changes in current clinical practice. PMID- 1454351 TI - Gonioscopic ab interno laser sclerostomy. A pilot study in glaucoma patients. AB - PURPOSE: The purpose of this study is to evaluate the safety and efficacy of gonioscopic ab interno laser sclerostomy (GLS) in patients with glaucoma. METHODS: The technique of GLS involves iontophoresis of methylene blue dye (1%) at the limbus to focally dye the sclera and to provide subsequent delivery of 10 microsecond pulsed laser energy to the dyed area through a goniolens. The laser emits at 660 nm, a wavelength that is maximally absorbed by the methylene blue dye. Patients were evaluated for fistula formation, intraocular pressure (IOP) reduction, and adverse sequelae. Thirty-eight treatments were performed in 35 eyes. RESULTS: Successful complete sclerostomies were achieved in 21 eyes (55%), which was associated with an acute mean reduction in IOP of 23 mmHg. Mean preoperative IOP for all patients was 35 mmHg, and 1 hour after treatment it was reduced to 18.5 mmHg. In 4 of the 38 treatments, there was no acute IOP reduction, and these eyes were judged as failures. The mean follow-up time was 8.2 months with a maximum follow-up of 15 months. By 9 months, 50% of patients had an IOP of 22 mmHg or lower. The number of antiglaucoma medications decreased from 3.1 to 1.7 for all eyes over the 15-month follow-up period. Hyphemas (13%) were the only major complication, and these resolved spontaneously. In only one case did the IOP increase after the procedure. CONCLUSION: The results of this trial indicate that GLS is technically feasible, and preliminary results of IOP control are promising. PMID- 1454352 TI - Molluscum contagiosum of the eyelids in patients with acquired immune deficiency syndrome. AB - BACKGROUND: Infection with molluscum contagiosum has been reported in patients with acquired immune deficiency syndrome (AIDS). Involvement of the eyelids by molluscum in patients with AIDS has rarely been mentioned. METHODS: Two patients with AIDS presented with eyelid molluscum contagiosum. Detailed examination and follow-up was performed. RESULTS: One patient had noted ocular irritation with epiphora for several weeks and showed a typical viral keratoconjunctivitis in both eyes. The other patient progressed to confluent masses involving the entire lower eyelid on one side. Removal of the lesions by surgery and cryotherapy was followed by recurrences in both patients within 6 to 7 weeks, the incubation period for this viral infection. CONCLUSION: Molluscum contagiosum can form confluent lesions on the eyelids in patients with AIDS, which may cause a keratoconjunctivitis. Local removal of molluscum eyelid nodules appears to be of limited long-term value in patients with T-cell immunodeficiency. PMID- 1454354 TI - The evolution of aminoacyl-tRNA synthetases, the biosynthetic pathways of amino acids and the genetic code. AB - In this paper the partition metric is used to compare binary trees deriving from (i) the study of the evolutionary relationships between aminoacyl-tRNA synthetases, (ii) the physicochemical properties of amino acids and (iii) the biosynthetic relationships between amino acids. If the tree defining the evolutionary relationships between aminoacyl-tRNA synthetases is assumed to be a manifestation of the mechanism that originated the organization of the genetic code, then the results appear to indicate the following: the hypothesis that regards the genetic code as a map of the biosynthetic relationships between amino acids seems to explain the organization of the genetic code, at least as plausibly as the hypotheses that consider the physicochemical properties of amino acids as the main adaptive theme that lead to the structuring of the code. PMID- 1454355 TI - [Three decades of roentgen-diagnosis of the upper digestive tract in the light of modern endoscopy]. AB - The author commemorating professor Geza Hetenyi, discusses the relation of endoscopy and x-ray diagnostic. He observes that the spreading of recent fibre optical endoscopes did not solve the problem of the early gastric cancer diagnosis. The experiences of the author based on his practice for several decades, data from the literature and, especially, the Japanese results show that x-ray did not lose its position but rather strengthened it in the diagnostics of the upper gastrointestinal tract. For examinations at identical levels, both diagnostic methods have equal opportunities to reveal gastric cancer at an early stage. In accordance with the type variety of early gastric cancer, the author discusses the relationship between early gastric cancer and gastric ulcer, and he proposes a rational algorithm for its diagnosis and follow-up. He shows that the most effective method for the diagnosis of the upper gastrointestinal tract is a reasonable combination of all available methods, and "primus inter pares" of them is x-ray examination, in addition to endoscopy. PMID- 1454356 TI - [Varicella pneumonia in adults]. AB - The authors treated 93 adult patients (83 male, 10 female) with varicella from 1st June 1987 to 30th April 1991. 13 patients had varicella pneumonia, two patients died. Special attention has been focused upon the diagnostic and prognostic problems, including bacterial superinfection. Authors stress the importance of the early diagnosis and treatment and discuss in detail the recent therapeutical and prophylactic opportunities. PMID- 1454357 TI - [Spontaneous and cytostatic therapy induced chromosome aberrations in testicular cancer patients]. AB - Chromosomal aberrations were studied in peripheral blood lymphocytes from only surgery treated testicular cancer patients and treated with chemo- and/or radiotherapy. A distinct increase in spontaneous aberration frequency over the level of 27 healthy controls in 27 patients treated with surgery alone was found. Our data suggest the existence of a certain degree of chromosome instability, which may be a factor to the development of testicular tumour. The frequency of aberrant cells was much higher in 102 treated patients than in the controls. The decrease in aberrant cells was only time-dependently gradual in VPB and X-ray treated patients, while the second line combined treatment modalities caused the highest frequency of aberrant cells in the first two years after the end of courses. The possible relationship between the persistence of chromosomal aberrations and the development of malignancies are discussed in this paper. PMID- 1454353 TI - Experimental studies on the origin of the genetic code and the process of protein synthesis: a review update. AB - This article is an update of our earlier review (Lacey and Mullins, 1983) in this journal on the origin of the genetic code and the process of protein synthesis. It is our intent to discuss only experimental evidence published since then although there is the necessity to mention the old enough to place the new in context. We do not include theoretical nor hypothetical treatments of the code or protein synthesis. Relevant data regarding the evolution of tRNAs and the recognition of tRNAs by aminoacyl-tRNA-synthetases are discussed. Our present belief is that the code arose based on a core of early assignments which were made on a physico-chemical and anticodonic basis and this was expanded with new assignments later. These late assignments do not necessarily show an amino acid anticodon relatedness. In spite of the fact that most data suggest a code origin based on amino acid-anticodon relationships, some new data suggesting preferential binding of Arg to its codons are discussed. While information regarding coding is not increasing very rapidly, information regarding the basic chemistry of the process of protein synthesis has increased significantly, principally relating to aminoacylation of mono- and polyribonucleotides. Included in those studies are several which show stereoselective reactions of L-amino acids with nucleotides having D-sugars. Hydrophobic interactions definitely play a role in the preferences which have been observed. PMID- 1454358 TI - [Initial experience with ESWL therapy of pancreatic duct calculi]. AB - Extracorporeal shock wave lithotripsy of pancreatic stones was performed in four patients with chronic pancreatitis and a dilated duct system harbouring stones 5 12 mm in diameter. The stones were disintegrated by shock waves using a Dornier lithotripter in one or more sessions. Disintegration of stones was achieved in 4/4 patients, initial (6-11 months) relief of pain in 3/4 patients, and total clearance of pancreatic duct in 3/4 patients. No complications were observed. In the first patient in whom ESWL was not completely successful, underwent an operation: a longitudinal pancreato-gastrostomy and the stones were found completely disintegrated. From these early data they conclude that ESWL of pancreatic duct stones is a provisional new alternative for surgery in the treatment of chronic pancreatitis. PMID- 1454359 TI - [A successfully treated case of congenital hydrops by Kell-alloimmunization]. AB - The authors report a successfully treated case of congenital hydrops caused by Kell alloimmunization. It is very important the early proper therapy and to make difference between the non immune hydrops fetus and the hydrops caused by alloimmunization. It seems to be indicated--also in Hungary, as the other European countries--the introduction of the screening of irregular antibodies during the pregnancy. PMID- 1454360 TI - [Hereditary aspects of Scheuermann disease, or what guarantees the reliability of the clinician's genetic knowledge?]. PMID- 1454361 TI - [Nuchal edema as an ultrasonic sign of trisomy 21 during the first trimester of pregnancy]. PMID- 1454362 TI - Clinical contrast sensitivity chart evaluation. AB - Three different types of contrast sensitivity chart were used on normal patients by six optometrists in clinical practice. The charts were the Vistech, the Pelli Robson and the Cambridge low-contrast gratings test. We examine the data in terms of the differences between optometrists and the variation of contrast sensitivity with the age of the patient. There was a highly significant difference between the scores from different optometrists for all three charts. We attribute this to variability in measurement technique. There was also a highly significant effect of age for all three charts, with older observers tending to exhibit lower contrast sensitivity. On the Vistech chart, this sensitivity deficit was most pronounced at higher spatial frequencies. The level of redundant information in the tests is discussed. PMID- 1454363 TI - Use of scrolled text in a scanning laser ophthalmoscope to assess reading performance at different retinal locations. AB - A new technique is described for assessing reading performance using a scanning laser ophthalmoscope. Letters of different sizes and contrasts were projected onto specific retinal locations of normal and low vision observers. Successive letters were scrolled in a horizontal direction at different speeds through a 'window'. Throughout the experiments the subjects' fundus and the retinal location of the stimuli could be visualized. With this scanning laser ophthalmoscope text-scrolling computer program the subject does not search for adjacent letters, and because the eye is held relatively stationary the tedious eye movement analysis incurred in other studies is reduced. Five retinal areas were investigated in two normal observers. The percentage of letters correctly identified decreased with eccentricity, increased velocity of the text and reduced text contrast. The reading performance of two patients, one with age related macular degeneration and the other with juvenile macular disease, was investigated. Decrements in performance were related to morphology of the lesions. PMID- 1454364 TI - Intraocular pressure measurement in children using the Keeler Pulsair tonometer. AB - A study to determine whether Keeler Pulsair tonometry is a feasible alternative to tonometry under general anaesthesia in children was undertaken. We recruited 53 children aged from 6 months to 9 years old. Readings were obtainable from 78% and a complete set of four readings from each eye was obtained from 45% of the group in an out-patient setting. Averaged Pulsair measurements agreed well with Perkins applanation tonometry values under general anaesthesia. Techniques to improve compliance are discussed. In conclusion, the Pulsair tonometer is a viable method for obtaining estimates of intraocular pressure in children in this age-group. PMID- 1454365 TI - Effect of restriction of the binocular visual field on driving performance. AB - The importance of the visual field on driving performance was investigated. This was undertaken by simulating binocular visual field defects for a group of young normal subjects and assessing the impact of these defects on performance on a driving course. Constriction of the binocular visual field to 40 or less, significantly increased time taken to complete the course, reduced the ability to detect and correctly identify road signs, avoid obstacles and to manoeuvre through limited spaces. Accuracy of road positioning and reversing were also impaired. Constriction of the binocular visual field did not significantly affect speed estimation, stopping distance, or the time taken for the reversing and manoeuvring tasks. The monocular condition did not significantly affect performance for any of the driving tasks assessed. PMID- 1454366 TI - Effect of induced fixation disparity on binocular visual acuity. AB - Fixation disparities were artificially created for distance vision by prisms, and the monocular and binocular visual acuities were measured. The normal approximate 10% improvement in binocular visual acuity compared to monocular visual acuity, deteriorated in proportion to the amount of fixation disparity created by the prisms. This was true in both eso- and exo-disparity, although not to the same extent. PMID- 1454367 TI - Spatial adaptation to text on a video display terminal. AB - We employed vertical sinusoidal test gratings to search for spatial adaptation to lower-case text presented on a standard video display terminal. The parameters of the contrast sensitivity test were selected on the basis of waveform analysis of horizontal spatial luminance profiles of the text. We found that subjects exhibited a small (4-5 dB), but significant, frequency-specific spatial adaptation consistent with the frequency spectrum of the stimulus. The theoretical and practical significance of this finding is discussed. PMID- 1454368 TI - Negative feedback control model of proximal convergence and accommodation. AB - A comprehensive model has been developed to illustrate the interactions between the observer and the surrounding environment in the control of oculomotor responses to distance or 3-D space. Accommodation and vergence respond to both spatiotopic (body reference) proximal percepts and retinotopic (eye referenced) physical stimuli of blur and disparity. Both spatiotopic and retinotopic stimuli are derived respectively from perceptual and physical correlates of negative feedback for eye position. The spatiotopic and retinotopic stimulus errors are combined in the feedforward path and drive a common oculomotor controller which has a phasic-tonic organization. Spatiotopic and retinotopic stimuli are shown to be effective over complementary operating ranges. Perceptual spatiotopic errors of gaze provide optimal stimuli for near responses to large depth intervals whereas physical-retinotopic cues of blur and disparity provide quantitative information about small binocular fixation errors. Small dynamic variations of target distance are sensed both spatiotopically and retinotopically. Coarse and fine spatiotopic errors of gaze are processed differently. Large spatiotopic errors are sampled intermittently at the beginning of the near response, whereas small retinotopic position errors and spatiotopic velocity errors are sampled continuously throughout the near response. Former reports of empirically observed higher velocity of vergence responses to very large depth intervals is explained in terms of stimulus sampling modes rather than in terms of separate oculomotor control mechanisms. The model demonstrates a complementary function of top-down spatiotopic cues, which are used to initiate the near response, and bottom-up retinotopic cues, which are used to refine and complete the near response. Cross couplings by vergence-accommodation and accommodative-vergence serve to coordinate the components of the near response when feedback from sensed response of one motor system (i.e. vergence) is more accurate than that of the other motor system (i.e. accommodation). The model presented here is concerned primarily with the near response mediated by accommodation and disjunctive eye movements and not by the independent vergence mediated by non-conjugate or yoked saccades of unequal amplitude. PMID- 1454369 TI - Adaptation model of accommodation and vergence. AB - Both accommodation and vergence have been shown to exhibit adaptation after extended near viewing. Normally, when the stimulus to accommodation is removed, the accommodation system returns rapidly towards its tonic position. However, if the stimulus is removed after an extended focusing effort, the decay is much slower. A similar effect can be observed in the vergence system. After prolonged wearing of horizontal prisms, blockage of one eye results in a much slower decay of the vergence output towards its tonic value. No previous models have been shown to simulate quantitatively these effects. An interactive dual-feedback model of accommodation and vergence was developed to simulate the adaptive behaviour found experimentally. The unique feature of the model is that the output of each controller drives a dynamic adaptive component whose output governs the time constant of the controller. The model was able to simulate the rapid and slow decays following short and long viewing intervals in each of the accommodative and vergence systems. It also simulated adaptation during alternate binocular and monocular viewing under the accommodation closed-loop condition. Thus, this model can serve as the basis for detailed quantitative evaluation of adaptive behaviour in the accommodation and vergence systems. PMID- 1454370 TI - Time-averaged accommodation response to flickering stimuli. AB - Experiments are described in which the steady-state accommodation response versus stimulus curve was measured with an infrared autorefractor for high-contrast stimuli having a 100% square-wave temporal modulation of luminance in the frequency band 1-200 Hz. Slightly more accurate responses were found at frequencies approximately 50-100 Hz, i.e. above flicker fusion. The relevance of the results to practical situations in which flicker may be experienced is discussed. PMID- 1454371 TI - Compensatory eye movements during near fixation after fast adaptation to lenses. AB - When the eyes are converged on a near target, the gain of the vestibulo-ocular reflex (VOR) during a subsequent head rotation is dependent upon both the amount of vergence and the degree to which it is asymmetrical. In conditions without visual feedback, we measured the gain of the VOR in the right eye of observers as they rotated their heads to the right or left while viewing a target placed 22, 32.5 or 200 cm from the centre of head rotation. We then adapted the VOR to the magnifying effects of +5 D lenses, and retested the VOR under the former convergence conditions. We found an inverse relationship such that the greater the VOR gain due to convergence, the less the effect of the rapid adaptation to lenses. PMID- 1454372 TI - Effects of monochromatic and chromatic oblique aberrations on visual performance during spectacle lens wear. AB - An optical system is described which allows overall visual performance to be studied when the wearer of a spectacle lens views objects through the lens periphery. Performance with lenses of any refractive power can be explored without any need for subjects to have the appropriate complementary refractive errors. In comparison with the effects of dioptric defocus, transverse chromatic aberration (TCA) is found to cause a relatively greater degradation in contrast sensitivity at high spatial frequencies when tangentially-oriented gratings are observed. The relative importance of TCA appears to have been underestimated in some previous studies. As vision is found to be affected by both TCA and defocus, a careful compromise between chromatic and monochromatic aberrations is required. PMID- 1454373 TI - QROC curves and kappa functions: new methods for evaluating the quality of clinical decisions. AB - The application of statistical methods for measuring the ability of clinical judgements and tests to discriminate between normal and diseased patients is increasing in optometry and ophthalmology. This paper presents two new methods for assessing the quality of such diagnostic decisions. Both are based on measurement of the kappa coefficient of association and offer theoretical and practical advantages over traditional methods. The paper first introduces the family of kappa coefficients with examples of their calculation and application. The use of weighted kappa values for measuring test sensitivity and specificity is explained, and it is shown how the results may be plotted in the form of the QROC curve which enables different aspects of test discriminability to be represented graphically. Kappa functions are then proposed as an alternative method for representing and predicting test performance, having the advantage of identifying optimal test criteria in addition to providing measures of discriminability. The clinical application of the new methods is illustrated using data for the detection of glaucoma from measurements of intraocular pressure. PMID- 1454374 TI - Accommodative responses to eccentric and laterally-oscillating targets. AB - There is little information on the accommodative response to stimuli having naturalistic motion on the retina. In the present experiment, the steady-state accommodative response at various dioptric levels was assessed with a Hartinger coincidence optometer as sinusoidal frequency of a small target was systematically altered across the horizontal foveal region (+/- 2 degrees). The steady-state accommodative response became less accurate as target oscillation frequency increased, approaching the tonic accommodation level when the frequency was between 0.5 and 1 Hz (corresponding to peak velocities of 6.3 and 12.6 deg s 1, respectively). These results suggest that the accommodation system is reasonably robust to naturally-occurring retinal-image motion. PMID- 1454375 TI - Variation in ocular modulation and phase transfer functions with grating orientation. AB - For circular pupils of diameters < or = 2 mm the optical performance of the eye in monochromatic light is effectively diffraction-limited, so that its modulation transfer function (MTF) is essentially independent of grating orientation and its phase transfer function (PTF) is close to zero. For larger pupils, however, the wave aberration of the eye usually exceeds the Rayleigh quarter-wavelength limit. It is shown that the monochromatic MTF may then display marked variation with orientation and the associated PTFs can be non-zero. The exact effects vary markedly with the individual subject. In white light additional asymmetries may occur due to transverse chromatic aberration. PMID- 1454376 TI - Scheme for the calculation of ocular components in a four-surfaced eye without need for measurement of the anterior crystalline lens surface Purkinje images. AB - The computing scheme described in this paper allows calculation of the internal radii of the human eye on the assumption that it possesses four (two corneal and two lenticular) axially aligned spherical surfaces separated by homogeneous optical media. It involves measurement of Purkinje images I, II and IV. This approach is novel in that it accounts for the contribution of the posterior corneal surface and does not require measurement of the Purkinje images arising from the anterior crystalline lens surface which are notoriously poor in quality. PMID- 1454377 TI - Keratoreformation by contact lenses after radial keratotomy: a re-analysis. AB - A recent paper analysed change in refraction and corneal curvature associated with contact lens wear in patients who had had radial keratotomy at least a year beforehand. Conventional methods of analysis were used. This paper applies methods that have only recently become available. The results are clearer and less ambiguous. Formally, the analysis shows that there are significant mean changes in refraction (estimated to be +1.69/-0.50 x 105) and corneal power ( 0.66/-0.25 x 155). In spite of the difference between these two mean changes, the analysis shows that the change in refraction may be associated with change in the corneal power alone. There is no reason to believe that any other change is occurring in the eye. Care needs to be executed in assigning a causative role to contact lenses in changing refraction and corneal curvature. Almost certainly the lenses do have such a role but the analysis does not formally allow an unequivocal conclusion concerning that role. PMID- 1454378 TI - Colorimeter for the intuitive manipulation of hue and saturation and its role in the study of perceptual distortion. AB - A simple optical method for mixing coloured light is described. The observer has intuitive and approximately independent control over hue and saturation at constant brightness. The method facilitates colour matching by unpracticed observers. It allows children with reading difficulties to select a colour that reduces perceptual distortion of text. The chromaticity coordinates of this colour vary from one observer to another but can be very specific. Complementary colours can exacerbate the distortions and induce pain. For the majority of children reporting beneficial perceptual effects, the u' coordinate is less than 0.25. PMID- 1454379 TI - Progressive addition lens channel dimension as a function of addition power. PMID- 1454380 TI - Mean visual acuity. PMID- 1454381 TI - What should medical students learn about pain? PMID- 1454382 TI - Postoperative analgesia: pain by choice? The influence of patient attitudes and patient education. AB - Postoperative pain control can be unsatisfactory for a variety of reasons, including patients' attitudes towards pain treatment itself. To assess patients' expectations and their influence on postoperative analgesia, as well as the prevalence of pain following common gynaecological surgery, a prospective study was performed in 166 patients with either abdominal hysterectomy, mastectomy, laparoscopy or uterine curettage. After a first postoperative period with routine on-demand analgesia, a nurse specialised in pain treatment discussed the purposes and risks of pain treatment with the patients and cared for these patients in the second, subsequent study period. Following this discussion, 30 of 40 patients refusing analgesics in the first study period agreed to be given pain medication. In the groups with hysterectomy or mastectomy, pain control improved in the second postoperative period, even though the doses of analgesics administered were generally lower. Education of patients regarding the aims and risks of pain therapy is an essential part of pain control and can lead to an improvement of postoperative analgesia. PMID- 1454383 TI - Chronic pain, relationships and illness self-construct. AB - A standardised illness self-construct repertory grid was used to evaluate relationships between people with chronic pain and the person to whom they felt closest. The 'Closest Other' was used to evaluate a wider range of relationships than generally included in research on 'spouse' reactions to chronic pain. The illness self-construct repertory grid indicated that closest others tended to place illness more centrally in the life of the individual with pain than did the person who had pain. The repertory grid provided information about the relationship which was not available from responses to open-ended questions. The statistical and theoretical assumptions of repertory grid technique make it ideal for intensive study of small groups or individuals best suited to clinical settings and not for screening large numbers of subjects. PMID- 1454384 TI - The Toddler-Preschooler Postoperative Pain Scale: an observational scale for measuring postoperative pain in children aged 1-5. Preliminary report. AB - This study evaluates the reliability and validity of the Toddler-Preschooler Postoperative Pain Scale (TPPPS), an observational scale developed to be a clinically useful measure of postoperative pain in children aged 1-5 years. The TPPPS consists of 7 items divided among 3 pain behavior categories: (1) Vocal pain expression; (2) Facial pain expression; and (3) Bodily pain expression. These items were derived from preliminary studies by the authors and from other observational studies of children's pain behavior. Seventy-four children between the ages of 12 and 64 months seen for inguinal hernia or hydrocele repair were the subjects of the study. Subjects were observed postoperatively for six 5-min intervals, commencing with their awakening from anesthesia, using the TPPPS. Two raters independently observed 28 of the children to assess inter-rater reliability. Validity was assessed by relating TPPPS scores to the timing and type of analgesics used, visual analog and numerical scale pain ratings made by parents and nurses, and perioperative vital signs. The TPPPS was found to possess satisfactory internal reliability (Cronbach's alpha = 0.88). Inter-rater reliability was good, with kappas for the pain behavior items ranging from 0.53 to 0.78. Preliminary evidence of the scale's validity is provided by the sensitivity of the scale to analgesic regimen, the convergence between TPPPS scores and nurse and parent ratings of postoperative pain, and the associations found between TPPPS scores and perioperative vital signs. PMID- 1454385 TI - Evaluation of constricted affect in chronic pain: an attempt using the Toronto Alexythymia Scale. AB - The Toronto Alexythymia Scale (TAS) was applied as a potential measure of constricted affect among a sample of patients with chronic, non-malignant pain (n = 195). As previously demonstrated with non-clinical samples, the scale was found to possess moderate reliability with two principal internal factors. These factors seemed to reflect social introversion and a lack of proneness to fantasy. There was a moderate, negative association between them. The domain sampled by the TAS was apparently heterogeneous, with total scores showing no relationship to reported disability or pain intensity and a low relationship to reported distress. These results suggest potential limitations of the TAS and the alexythymia construct as means for evaluating constricted affect that accompanies chronic pain. PMID- 1454386 TI - Transdermal fentanyl and initial dose-finding with patient-controlled analgesia in cancer pain. A pilot study with 20 terminally ill cancer patients. AB - This pilot study evaluated the efficacy and side effects of a combination of initial patient-controlled analgesia (PCA) for dose-finding with transdermal fentanyl administration. Twenty inpatients, requiring strong opioids for severe cancer pain, received intravenous fentanyl on an on-demand basis over a 24-h period. The amount of fentanyl administered was then used as a guideline for selecting a suitable transdermal therapeutic system (TTS) on the 2nd day, which remained in place for 3 days. The size of a 2nd TTS, being used from day 5 to 7, was adjusted according to the amount of supplementary intravenous fentanyl doses on day 3. From day 4 to 7 intravenous fentanyl was stopped, and subcutaneous morphine was made available as a rescue medication. A standardized adjuvant medication was allowed. Pain intensity, pain relief, quality of sleep, mood, general state of health, activity, mobility, rescue morphine consumption and side effects were assessed using a diary after baseline pain and symptoms were recorded. Vital functions were monitored and fentanyl plasma levels were measured daily in 15 patients. The use of TTS fentanyl in combination with initial dose titration using PCA gave rapid and statistically significant pain relief. Patient compliance and acceptance were excellent. In the absence of severe side effects the main complaints were dryness of the mouth and constipation. Increasing pain intensity and increasing supplementary morphine requirements as well as decreasing plasma fentanyl levels on day 7 may indicate that conversion ratios from intravenous to transdermal administration should be increased or that TTS should be changed earlier.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454387 TI - Influence of alprazolam on opioid analgesia and side effects during steady-state morphine infusions. AB - The primary purpose of this study was to examine whether alprazolam pretreatment can increase the analgesic potency of morphine without increasing opioid side effect intensities. We employed computer-controlled, variable-rate morphine infusions based on each subject's pharmacokinetic profile for morphine derived from a tailoring bolus dose of the drug administered 1 or 2 weeks before the infusion test sessions. On each of 2 test days, we used dental electrical stimulation to determine stimulus intensity that produced consistent reports of strong (but tolerable) pain; this intensity was used for the rest of that session. Then, we measured baseline (no drug) pain intensity reports, pain related evoked potentials recorded from vertex, and other parameters typically affected by opioids (subjective side effects). We administered alprazolam (1 mg) or placebo (lactose) orally to the subject and then repeated the test battery 30 min later. One hour after the alprazolam or placebo dose, we initiated the tailored morphine infusion to reach target plasma morphine concentration plateaus of 16, 32 and 64 ng/ml (45-min duration each) on both test days. The test battery used during baseline was then repeated at each target concentration plateau. The order of alprazolam versus placebo pretreatments was counterbalanced across subjects and known only to the investigator operating the infusion system. Results suggest that alprazolam at the dose studied did not alter analgesic potency of morphine. However, alprazolam did clearly decrease the intensity of nausea reported by subjects during and after termination of the morphine infusions. Of special interest, alprazolam alone (30 min after oral dosing) decreased evoked potential amplitude consistently without affecting pain intensity reports.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454388 TI - Intracerebroventricular micro-injections of non-steroidal anti-inflammatory drugs abolish reperfusion hyperalgesia in the rat's tail. AB - Prostaglandins are mediators of reperfusion hyperalgesia; their site of action may be in the periphery, in the central nervous system, or both. We have investigated whether prostaglandins play a role in the central nervous system during reperfusion hyperalgesia, by intracerebroventricular (i.c.v.) micro injection of non-steroidal anti-inflammatory drugs (NSAID), to inhibit local prostanoid synthesis. We induced tail ischaemia in conscious rats by applying an inflatable cuff at the base of the tail. The cuff was released at the first signs of co-ordinated escape behaviour. Responses to a noxious thermal stimulus were assessed, by measuring tail flick latency following immersion of the tail in water at 49 degrees C, prior to and immediately after release of the tourniquet. Tail flick latency decreased significantly following ischaemia, that is there was post-ischaemic reperfusion hyperalgesia. Intracerebroventricular micro-injection of NSAID prior to applying the tourniquet had no effect on the co-ordinated escape behaviour during ischaemia or on the tail flick latency after application of a sham tourniquet (uninflated cuff). However all the drugs abolished the hyperalgesia evident during reperfusion. Doses required to abolish hyperalgesia were 0.001 mg/kg indomethacin, 0.08 mg/kg dipyrone, 0.09 mg/kg ibuprofen, 0.2 mg/kg diclofenac sodium and 0.2 mg/kg paracetamol. These doses are 2-3 orders of magnitude less than those necessary to abolish reperfusion hyperalgesia when the same drugs are administered systemically. Our results indicate that the development of reperfusion hyperalgesia of the rat's tail depends on the synthesis of prostanoids within the central nervous system. PMID- 1454389 TI - The effects of a non-competitive NMDA receptor antagonist, MK-801, on behavioral hyperalgesia and dorsal horn neuronal activity in rats with unilateral inflammation. AB - The involvement of NMDA receptors in rats with peripheral inflammation and hyperalgesia was evaluated by administration of the non-competitive NMDA receptor antagonist, MK-801. Inflammation and hyperalgesia was induced by intradermal injection of complete Freund's adjuvant (CFA) or carrageenan into the left hind paw. The latency of paw withdrawal from a thermal stimulus was used as a measure of hyperalgesia in awake rats. MK-801 (1.6 mg/kg, i.p., or 31.5 micrograms, intrathecal) significantly attenuated thermal hyperalgesia and reduced its duration in comparison to saline-injected rats (P less than 0.05). The receptive field size of nociceptive-specific and wide-dynamic-range neurons in the superficial and deep spinal dorsal horn recorded 24 h after injection of CFA was significantly reduced to 73 +/- 6% (P less than 0.05, n = 8) and 74 +/- 4% (P less than 0.05, n = 8) of control values, respectively, by a cumulative dose of 3 mg/kg of MK-801 (i.v.). MK-801 (2 mg/kg) prevented the expansion of the receptive fields of dorsal horn neurons recorded 5 +/- 0.4 h (n = 5) after intradermal injection of CFA as compared to saline-injected rats (P less than 0.05). MK-801 had no significant effect on receptive field size of dorsal horn neurons in rats without CFA-induced inflammation but blocked a transient expansion of the receptive fields induced by 1 Hz, C-fiber intensity electrical stimulation of the sciatic nerve. The background activity and noxious heat-evoked response of dorsal horn neurons in rats with CFA-induced inflammation were primarily inhibited and noxious pinch-evoked activity was both facilitated and inhibited by the administration of MK-801. These results support the hypothesis that NMDA receptors are involved in the dorsal horn neuronal plasticity and behavioral hyperalgesia that follows peripheral tissue inflammation. PMID- 1454390 TI - Putative mechanisms of buspirone-induced antinociception in the rat. AB - Intraperitoneal administration of the serotonin 5-HT1A agonist, buspirone (1-5 mg/kg), produced dose- and time-related core hypothermia that was coincident with analgesia against a thermally noxious stimulus. Surface body temperature was not altered by buspirone. The 5-HT1A antagonist, NAN-190 (2 mg/kg, s.c.), blocked both hypothermic and analgesic effects, while systemic administration of the opioid antagonist, naloxone (1 mg/kg, s.c.), did not change the pattern of buspirone-induced hypothermia or analgesia. The apparent lack of opioid involvement and the documented role of the 5-HT1A receptor system in neuroendocrine substrates of thermoregulation and pain modulation prompted study of adrenal function in these buspirone-induced effects. Buspirone (5 mg/kg, i.p.) produced significant elevations in plasma epinephrine (EPI) and corticosterone (CST). Bilateral adrenalectomy reduced both control and buspirone-elevated EPI and CST levels and attenuated the antinociceptive, but not hypothermic, effects of buspirone (1-5 mg/kg, i.p.). Administration of the phenylethanolamine-N methyltransferase (PNMT) inhibitor, dichloromethylbenzylamine (DCMB: 25 mg/kg, i.p.) reduced basal and buspirone-elevated plasma EPI, but not CST levels. This treatment did not affect buspirone-induced hypothermia, while significantly reducing buspirone antinociception. Pretreatment with the CST synthesis inhibitor, aminoglutethemide (AG: 2 x 25 mg/kg, i.p.), reduced plasma CST levels while not significantly affecting EPI. AG pretreatment did not alter the hypothermic effects of buspirone, but attenuated antinociception produced by the highest buspirone dose. The AG-induced reductions of buspirone antinociception were less than those effects produced by DCMB treatment. These data suggest that buspirone-induced antinociception may be a non-opioid, adrenally mediated co- and/or epi-phenomenon to core hypothermia evoked by 5-HT1A receptor agonism. PMID- 1454391 TI - The placebo effect: an unpopular topic. PMID- 1454392 TI - Effects of selective neurotoxic lesion of lumbosacral serotonergic and noradrenergic systems on autotomy behaviour in rats. AB - Male rats underwent unilateral ligation and transection of the sciatic and saphenous nerves 2, 7 or 14 days after being injected intrathecally (at the thoracolumbar junction) with 6-hydroxydopamine (6-OHDA), 5,6-dihydroxytryptamine (5,6-DHT) or vehicle, and the development of autotomy was monitored. The effects of both neurotoxins on cervicothoracic (C5-T1) and lumbosacral (L1-S1) norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) spinal cord levels were analysed by HPLC in separate groups of rats. 6-OHDA treatment (20 micrograms/10 microliters) produced a rapid (from day 2) and significant (90-95%) fall in NE content only at L1-S1. 5,6-DHT administration (20 micrograms/10 microliters) produced a gradual (68%, 90% and 94%, at 2, 7 and 14 days, respectively) and selective depletion of 5-HT only at L1-S1. DA levels remained essentially unchanged after both neurotoxins. No differences in monoamine levels were detected among groups injected with vehicle. The main effects of neurotoxins on autotomy were: (1) a significant delay in the onset of autotomy in the rats injected with 6-OHDA 2 days before neurectomy; (2) a trend to autotomize earlier and more severely in the rats injected with 5,6-DHT 7 days before neurectomy and (3) an almost complete suppression of autotomy in the rats injected with 5,6-DHT 14 days before neurectomy. These results revealed that the expression of autotomy in rats can be modulated by interfering with spinal cord serotonergic activity and suggest new possible avenues for the treatment of certain specific pain diseases, such a phantom limb pain, by using selective agents capable of activating or blocking spinal cord serotonergic receptor subtypes. PMID- 1454393 TI - T-lymphocyte subsets in otherwise healthy patients with herpes zoster and relationships to the duration of acute herpetic pain. AB - T-lymphocyte subsets (CD3, CD4, and CD8 lymphocytes) in peripheral blood, parameters of cell-mediated immunity, were serially measured in 62 otherwise healthy Japanese patients with herpes zoster (HZ), and the findings were compared with those of 20 age-matched healthy controls who had had varicella but not HZ. Our objective was to elucidate whether there were changes in cell-mediated immunity, even in immunocompetent patients with HZ, and to investigate relationships between these variables and the duration of acute herpetic pain (AHP). All the patients underwent repeated sympathetic nerve blocks until pain was relieved. As compared with controls, there were slight increases in the percentages of CD4 lymphocytes (helper/inducer) and highly significant increases in the percentages of CD8 lymphocytes (suppressor/cytotoxic), resulting in marked decreases in CD4/CD8 ratios in the acute phase of HZ. The percentages of CD3 lymphocytes (pan-T lymphocytes) did not differ significantly. The duration of AHP was analyzed in 49 patients in whom T-lymphocyte subsets were measured more than twice. There was a weak but statistically significant positive linear correlation between age and the duration of AHP (r = 0.43, P < 0.01). There were statistically highly significant positive linear correlations between the number of days on which percentages of CD3 (r = 0.72, P < 10(-8)) and CD4 lymphocytes (r = 0.60, P < 10(-5)), and CD4/CD8 ratios (r = 0.62, P < 10(-5)) reached the maximum values after the onset of HZ and the duration of AHP. These correlation coefficients were higher than that between age and the duration of AHP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454394 TI - The simultaneous interview technique (SIT) and the codisciplinary model of chronic pain treatment. PMID- 1454395 TI - On the controversy of autotomy: a response to L. Kruger. PMID- 1454396 TI - Comments on Ward et al., PAIN, 44 (1991) 151-155. PMID- 1454397 TI - Does pre-operative fentanyl administration influence postoperative analgesia? PMID- 1454398 TI - Comments on Gong et al., PAIN, 48 (1992) 249-255. PMID- 1454399 TI - Comments on Swerdlow and Dieter, PAIN, 48 (1992) 205-213. PMID- 1454400 TI - The antinociceptive effects of intrathecally administered cannabinoids are influenced by lipophilicity. AB - Previous research has demonstrated that intravenously administered cannabinoids produce potent antinociception in rodents. The present study examined the ability of 16 cannabinoid analogs to produce antinociception and hypothermia after intrathecal administration. Fifteen of the compounds tested produced significant increases in the tail-flick response to radiant heat. This effect was stereoselective because N-methyl-dextronantradol, the inactive stereo-isomer of the potent cannabinoid analog N-methyl-levonantradol, failed to elevate tail flick latencies above baseline values. In general, the drugs tended to be more effective in producing hypothermia than antinociception. A positive correlation found between the ED50 values in producing antinociception and lipophilicity indicated that the most lipid-soluble drugs were the least active. In contrast, no apparent relationship between cannabinoid-induced hypothermia and lipophilicity was found. The finding that the antinociceptive effects of spinally administered cannabinoids is inversely related to lipophilicity is similar to that reported for the opiates. PMID- 1454401 TI - Quantitative sensory examination in human epidural anaesthesia and analgesia: effects of lidocaine. AB - To characterize the sensory effects of epidural lidocaine, 2 groups each of 10 human subjects received 25 ml of 2% lidocaine at the L1-L2/L2-L3 interspace (high lumbar group) or at the L3-L4/L4-L5 interspace (low lumbar group). Twelve quantitative sensory tests in the L5 and S1 dermatomes and leg extension strength were determined every 30 min for 3 h. Sensory and motor blockade were more pronounced in the low than in the high lumbar group. Sensory functions were blocked in the following order by epidural lidocaine: warm > cold > electrical stimuli. Perception of brief localized noxious stimuli was attenuated more than perception of noxious stimuli of longer duration and involving larger stimulus areas. It is suggested that both peripheral mechanisms (differential conduction blockade of afferent fibres) and central mechanisms (temporal and spatial summation) play a role in the sensory effects of epidural lidocaine. PMID- 1454402 TI - The role of stressful life events in the persistence of primary headache: major events vs. daily hassles. AB - This study investigated the role of major stressful life events vs. minor life events (i.e., daily hassles) in the persistence of primary headache. It was hypothesized that chronic headache patients (n = 83) would be characterized not so much by exposure to a continued surfeit of inherently major life events as by a tendency to appraise cognitively and emotionally any ongoing microstressor or daily hassle as being more arousing or impactful than headache-free controls (n = 51). As predicted, chronic headache patients reported a significantly higher frequency (P < 0.01) and density (P < 0.01) of daily hassles, but not of major life events, than controls. Furthermore, minor life events were significantly correlated with headache frequency (P < 0.001) and density (P < 0.001) but not with gender, age and headache history. In terms of item content, health-related hassles (e.g., trouble relaxing) were perceived as being the most stressful. Significant differences between headache subgroups (chronic tension-type headache, migraine, mixed headache) were found, with tension-type and mixed headache sufferers reporting a higher incidence and density of daily hassles than migrainous patients. It was concluded that daily hassles were significantly associated with the persistence of headache and might be a better life event approach to chronic headache than major stressful events. PMID- 1454403 TI - Cervicogenic headache, migraine without aura and tension-type headache. Diagnostic blockade of greater occipital and supra-orbital nerves. AB - The diagnostic value of greater occipital and supra-orbital nerve blockades in patients with cervicogenic headache, migraine without aura, and tension-type headache was investigated. The pain reduction after greater occipital nerve blockade was significantly more marked in the cervicogenic headache group than in the other categories. Moreover, pain reduction in the forehead was generally only found in the cervicogenic headache patients (77%). Pain reduction (in %) was significantly more marked following the greater occipital than the supra-orbital nerve blockade. The volume effect per se was evaluated by saline injection. This procedure did not result in distinct pain reduction. The effect obtained in cervicogenic headache is, accordingly, probably due to the local anaesthesia. The present results support the postulate that different pathogenetic factors probably are responsible for cervicogenic headache, tension-type headache, and migraine without aura. PMID- 1454404 TI - Long-term efficacy of combined relaxation: biofeedback treatments for chronic headache. AB - Thirty-four patients having chronic idiopathic headaches participated in a long term study comparing autogenic relaxation training alone (REL) with combinations of relaxation and electromyographic biofeedback (REL + EMG) or relaxation and temperature biofeedback (REL + TEMP). Assignment to treatment conditions was balanced on demographics and clinical characteristics, as well as headache classification according to muscle contraction or vascular headache symptomatology. The results indicate that REL + TEMP produced no additional improvements over REL following the 8-week treatment program, or at 6-month, or 12-month follow-up. However, REL + EMG produced significantly greater reductions in headache activity measures than the REL and REL + TEMP conditions at all post treatment time points. Headache activity continued to improve over the follow-up period independent of treatment condition. These data indicate that EMG biofeedback augments long-term clinical improvements in headache patients who undergo autogenic relaxation training. PMID- 1454405 TI - The formalin test: an evaluation of the method. AB - The formalin test for nociception, which is predominantly used with rats and mice, involves moderate, continuous pain generated by injured tissue. In this way it differs from most traditional tests of nociception which rely upon brief stimuli of threshold intensity. In this article we describe the main features of the formalin test, including the characteristics of the stimulus and how changes in nociceptive behaviour may be measured and interpreted. The response to formalin shows an early and a late phase. The early phase seems to be caused predominantly by C-fibre activation due to the peripheral stimulus, while the late phase appears to be dependent on the combination of an inflammatory reaction in the peripheral tissue and functional changes in the dorsal horn of the spinal cord. These functional changes seem to be initiated by the C-fibre barrage during the early phase. In mice, the behavioural response in the late phase depends on the ambient temperature. We argue that the peripheral tissue temperature as well as other factors influencing the peripheral inflammation may affect the response, possibly confounding the results obtained with the test. Furthermore, we discuss the methods of recording the response and the value of observing more than one aspect of behaviour. Scoring of several behavioural variables provides a means of assessing motor or sensorimotor function as possible causes for changes in behaviour. In conclusion, the formalin test is a valuable addition to the battery of methods available to study nociception. PMID- 1454406 TI - Dissociating spontaneous and deliberate expressions of pain: signal detection analyses. AB - Neuro-anatomical and behavioral findings suggest that spontaneous and deliberate facial expressions are regulated by separate systems. The present study examined whether spontaneous and deliberate expressions of pain could be distinguished and, if so, the dimensions on which they differ. Forty subjects were exposed to electric shocks that varied from painless to strong pain. They also simulated facial reactions to the same levels. Observers rated the apparent pain in subjects' expressions and whether they were feigned or genuine. Signal detection analyses indicated that the intensity of deliberate expressions was greater than spontaneous expressions at levels below strong pain. Observers were able to distinguish between deliberate and spontaneous expressions to a modest degree. The intensity of deliberate expressions was related to role-playing ability. The results suggest that deliberate and spontaneous expressions of pain probably differ in intensity, topography and temporal features. They suggest that facial expressions of pain have different determinants than other forms of pain behavior. PMID- 1454407 TI - A canonical correlation analysis of the influence of neuroticism and extraversion on chronic pain, suffering, and pain behavior. AB - The relationship between neuroticism and extraversion on the 4 major stages of pain processing, that of pain sensation intensity, pain unpleasantness, suffering, and pain behavior, were studied in 205 chronic pain patients (88 male and 117 female). Patients underwent psychological evaluation which included the Pain Experience visual analogue scales (VAS) (Price et al. 1983), NEO Personality Inventory (NEO-PI) (Costa and McCrae 1985), and the Psychosocial Pain Inventory (PPI) (Getto and Heaton 1980). Canonical correlation was used to control for pain sensation intensity in evaluating affective dimensions of pain and to control for neuroticism in assessing effects of extraversion on different stages and dimensions of pain. Neither neuroticism nor extraversion were related to pain sensation intensity. Only neuroticism was associated with pain unpleasantness. Personality factors had their greatest impact on stages 3 (suffering) and 4 (illness behavior) of pain processing. The results of multiple regression analyses indicated that life-long vulnerability to anxiety and depression is paramount in understanding the relationship between personality and suffering in chronic pain. These findings provide support for the idea that personality traits influence the ways in which people cognitively process the meanings that chronic pain holds for their life, and hence the extent to which they suffer. PMID- 1454408 TI - The relationship between spouse solicitousness and pain behavior: searching for more experimental evidence. AB - In this study 42 chronic back pain patients participated twice in a treadmill test. During 1 of these 2 sessions, the partner was present. Walking time, pain intensity ratings, and heart rate were measured before and after the tests. From the results of previous studies it was expected that, in the presence of a relatively solicitous spouse, patients would report more pain, would have a shorter walking time, and would exert themselves less physically. Spouse solicitousness was measured in 2 ways: from the patient's perspective as well as from that of the spouse. Results based on the patient's interpretation of his/her partner's responses are not in accordance with previous findings. Results based on the spouse's view demonstrate, however, that patients with solicitous spouses do, in fact, report more pain and walk for a shorter duration in the presence of the spouse than patients with relatively non-solicitous spouses. Theoretical and practical implications are discussed. PMID- 1454409 TI - The behavioral response to formalin in preweanling rats. AB - The behavioural response of rat pups, 1-20 days of age, to subcutaneous injection of formalin in a rear paw is described. Formalin-injected pups were compared to handled controls and to pups that received an injection of normal saline. Ongoing behaviour was recorded every 2 min for 60 min after injection. Injection of normal saline produced little disorganization of behaviour, although day-1, -3 and -6 pups did frequently flex the limb on the injected side early in the session. Injection of 10 microliters of 1% formalin depressed active and quiet sleep in pups 10 days old and younger. Much less disruption of sleep was observed in day-15 pups, and in day-20 pups it was necessary to increase the concentration of formalin to 2.5% to produce a consistent behavioural response. The specific responses of pups to formalin injection were flexion of the limb, shaking the limb, and licking the injected paw. Pups of all ages displayed all of these responses, but in pups younger than 10 days, only limb flexion was consistent. Shaking became a consistent response in day-10 pups and licking in day-15 and -20 pups. Non-specific behaviours (squirming, vigorous rear kicks with both hind limbs and convulsive whole body jerks) were markedly increased by formalin in younger pups with a developmental pattern: squirming and kicking in day-1 pups, kicking and jerking in day-3 to -15 pups. Non-specific behaviours decreased and specific behaviours increased with age. In addition, the overall intensity and duration of the response decreased with age. The biphasic time course of the response of adult rats to formalin injection did not appear until 15 days of age. PMID- 1454410 TI - Vagal afferent fibers excite upper cervical neurons and inhibit activity of lumbar spinal cord neurons in the rat. AB - Effects of electrical stimulation of the cervical vagus nerve were determined in cervical or lumbar spinal neurons in 27 rats anesthetized with pentobarbital. Ipsilateral cervical vagus stimulation (ICVS) increased activity of 44 neurons in the C1 segment. At the same stimulation parameters, contralateral cervical vagus stimulation (CCVS) either increased, decreased or did not affect activity of C1 neurons that were excited by ICVS. For C1 cells excited by both ICVS and CCVS, the mean latency for activation was significantly longer for CCVS than for ICVS, and ICVS produced a greater degree of excitation than CCVS. In segments C2-C6, 16 of 18 neurons were excited by ICVS and 2 were inhibited. However, CCVS did not excite the C2-C6 neurons but either inhibited or did not affect activity. In 6 cervical cells, a CCVS conditioning stimulus reduced the level of excitation by ICVS (test stimulus). Transection of the C2 or C3 dorsal roots did not significantly affect the excitatory vagal input to C1 cells. Excitatory somatic receptive fields were classified for 60 cervical spinal cells that responded to vagal stimulation. Most (87%) cells were excited by noxious pinch; 29 were wide dynamic range (WDR) cells and 21 were high threshold cells. In contrast to upper cervical neurons, spinothalamic tract (STT) and spinal cells in lumbar segments were not excited by ICVS or CCVS at the stimulation parameters used in this study, but were primarily inhibited by vagal stimulation. Results of this study showed that a group of cells in upper cervical segments were excited by vagal afferents. This excitatory vagal input reaches the C1 segment primarily via an ipsilateral, supraspinal route. PMID- 1454411 TI - [The parasitism of the itch mite Sarcoptes scabiei (Acariformes: Sarcoptidae)]. AB - The life cycle of the itch mite Sarcoptes scabiei (L.), an intracutaneous parasite of man and animals, has been studied. The paper concerns morphological adaptations, embryonal and postembryonal development, life cycle pattern, scabious passage as a reproductive formation, invasive stages, feeding, reproduction and topical relationships with the host, distribution and survival in the environment. PMID- 1454412 TI - [The organization of purine and pyrimidine nucleotide biosynthesis in Sporozoa (Protozoa)]. AB - Analysis of peculiarities in organization and functioning of metabolic ways of biosynthesis of purine and pyrimidine nucleotides in representatives of Sporozoa type has shown that molecular aftereffects of adaptation to intracellular parasitism in unicellular eukaryotes consists in the increase in the level of molecular organization, loss of some metabolic path ways and some enzymes, origin of a new metabolic system, a host-parasite one. Functioning of this system is achieved due to developing by the parasite mechanisms that are similar to the host's ones. PMID- 1454413 TI - [Nematodirus nemorhaedi sp. n. (Nematoda: Trichostrongylidae) from the Amur goral Nemorhaedus caudatus raddeanus]. AB - Nematodirus nemorhaedi sp. n. is described. The new species was found in the small intestine in three long-tailed gorals from the Maritime Territory. The species differs from other species of the genus, parasites of ungulates, by very large (over 1.5 mm) spicules and characteristic structure of their distal end in males; by long (about 1 mm) ovijector in females and by a specific combination of characters of synloph, genital bursa in males, sizes of body, structure of vulva, sizes and shape of eggs and tail in females. PMID- 1454414 TI - [The dependence of the quantitative indices of the infection of Yamal rodents with ectoparasites on the method of trapping]. AB - Comparative data on the effect of the method of catching rodents in tundra on the composition and quantitative indices of parasite fauna are analyzed. The catching of rodents by means of traps in the isolated areas results in 30 to 60% decrease in the indices of abundance of gamasid mites as compared to the catching of animals with dogs. The infection of dead animals with fleas is 4 times lower than that of living ones. PMID- 1454415 TI - Opposite influences of host anaemia on blood feeding rate and fecundity of mosquitoes. AB - We tested a theoretical model based on the physics of capillary flow and confirmed that anaemia accelerates blood intake in the yellow-fever mosquito, Aedes aegypti (L.). We also investigated the influence of anaemic blood on egg production of mosquitoes and found that it has a negative influence on fecundity. Based strictly on egg production and the physics of fluid intake, we propose that although anaemia associated with blood-borne parasites may be detrimental to mosquitoes that can engorge to repletion in one session, it may be beneficial to those interrupted before repletion because the greater quantity of the bloodmeal may compensate for its lower quality. Epidemiological consequences are discussed but require further inquiry. PMID- 1454416 TI - Endogenous superoxide dismutase activity in two Babesia species. AB - Babesia hylomysci and B. divergens were studied for superoxide dismutase (SOD) activity by enzyme assay and isoelectric focusing (IEF). In the two Babesia species, parasite-associated SOD is cyanide-insensitive and inhibited by H2O2, indicating that iron is the cofactor metal. Measurements of SOD activity from purified parasites show that the SOD activity detected in Babesia is, for the main part, due to an endogenous enzyme. PMID- 1454417 TI - Axenic cultivation and characterization of Leishmania mexicana amastigote-like forms. AB - A new method is described which has made possible the long-term axenic cultivation of Leishmania mexicana amastigote-like forms in Schneider's Drosophila medium supplemented with 20% (v/v) foetal calf serum. Unlike previous methods, it utilizes direct culture of parasites obtained from the lesions of infected animals rather than adaptation of promastigotes in vitro. Ultrastructural (possession of megasomes), biochemical (cysteine proteinase activity and gelatin SDS-PAGE banding pattern) and infectivity (in vivo) data are presented which show the close similarity of the cultured forms to lesion amastigotes. The axenically cultured forms grew optimally at a temperature of 32 33 degrees C, providing further evidence for their amastigote nature. It was found that adjustment of the pH of the growth medium to 5.4 was required in order to retain the amastigote morphology of the cultured parasites. This supports the notion that leishmanial amastigotes are acidophiles. PMID- 1454418 TI - The ENZYMEBA test: detection of intestinal Entamoeba histolytica infection by immuno-enzymatic detection of histolysain. AB - We describe a new, improved test for the detection of intestinal infection by Entamoeba histolytica. The test depends upon immunoadsorption of the E. histolytica cysteine proteinase, histolysain, from faecal samples, and subsequent visual detection of the enzyme by a colour reaction. With samples from 200 volunteers, results agreed closely with those obtained by the conventional microscopic technique, and there were no false positive reactions with samples containing other parasites. The test is suitable for use either in the laboratory or in the field. PMID- 1454419 TI - Circulating antibodies to histolysain, the major cysteine proteinase of Entamoeba histolytica, in amoebic liver abscess patients. AB - A solid-phase enzyme immunoassay (EIA) was used to detect circulating antibodies to histolysain, the major cysteine proteinase of Entamoeba histolytica. Serum samples from 40 healthy controls, 33 asymptomatic E. histolytica cyst passers and 22 patients with amoebic liver abscess were tested. Antibodies to histolysain were found in 72.7% of cases of amoebic liver abscess, 18.1% of the cyst passers and 2.5% of healthy controls, which suggests that a humoral immune response is induced by histolysain during amoebic liver abscess. PMID- 1454420 TI - Purification and characterization of a 47 kDa protease from Schistosoma mansoni cercarial secretion. AB - Fractionation of Schistosoma mansoni cercariae gland secretion on a Sephadex G 150 column followed by a Superose-12 column in an FPLC system, isolated a 47 kDa protease which migrated as a single band on SDS-PAGE gels. A monoclonal antibody (MAb) was produced which recognizes only the 47 kDa protease, and an immuno affinity column with the MAb was used to isolate the protease. The 47 kDa protease showed activity on several macromolecules such as elastin and collagen type VI besides gelatin and casein. This suggests that this enzyme can be one of the enzymes that might facilitate invasion of the cercariae through host skin. The optimal pH of the protease against the synthetic substrate, Ac-Phe-Arg-Nan, in Tris-HCl buffer was 10. Experiments with protease inhibitors indicate that the purified enzyme is a serine protease. PMID- 1454422 TI - The effects of computer-controlled shadow stimuli on the success of cercarial transmission by Cryptocotyle lingua (Digenea: Heterophyidae). AB - Pectoral fins from juvenile rainbow trout (Oncorhynchus mykiss) were used in a bioassay, the object of which was to quantify the effect of simulated shadow stimuli on the transmission success of the cercariae. For a period of 60 min, parasites and fins were exposed to a sequence of computer-controlled shadow stimuli, continuous light or total darkness, and subsequently the number of infections was counted. Trials were conducted with cercariae 1, 12 and 24 h old. Within the constraints of the experimental procedure, shadows were found to increase significantly the number of infections achieved by the 12-h-old parasites. As the cercariae aged, their ability to infect host tissue declined. The relevance of these results to transmission in the natural environment is discussed. PMID- 1454421 TI - On the use of age-intensity data to detect immunity to parasitic infections, with special reference to Schistosoma mansoni in Kenya. AB - We consider two phenomena, related to the host age-intensity profiles of parasitic infections, which have been suggested to be indicative of acquired immunity: (i) a lower age of peak intensity among more intensely infected hosts; and (ii) a decline with age in the dispersion of the distribution of parasites between hosts. We demonstrate that these phenomena occur among Kenyan schoolchildren infected with Schistosoma mansoni, although the magnitude of both is small. We also examine the mathematical models underlying these predictions and conclude that both phenomena are possible in the absence of acquired immunity or, indeed, in the absence of any density-dependent effect. In our opinion, insufficient attention has been focused upon mathematical models, describing the null hypothesis, i.e. density-independent models. In particular, we regard the usual assumptions made for the two stochastic components of these models, describing the heterogeneity between hosts and the probabilistic nature of infection and death of parasites, as too rigid and unrealistic. We demonstrate that deviation from these assumptions undermines the qualitative distinctions between models which describe acquired immunity or density dependence and those which are density-independent. PMID- 1454423 TI - The dynamics of trickle infections with Ancylostoma ceylanicum in inbred hamsters. AB - Trickle infections with a hamster-adapted strain of the hookworm Ancylostoma ceylanicum were studied by administering doses of 5-30 larvae twice weekly to inbred DSN hamsters. The worm burdens were regulated at very low levels, and this was found to be independent of the size of the infective dose. It is likely that there is some turnover of adult worms during trickle infection, as larvae of all stages were recovered from most time-points. This regulation is immunologically mediated and both the worm burdens and fecundity were increased in hamsters that were immunosuppressed by cortisone treatment. A trickle infection regime also induced a 67% protective immunity to a single subsequent challenge. The resistance that occurred during trickle infections was, however, incomplete, and some worms were found to survive in hamsters that had been repeatedly infected for over 10 weeks. Thus, although hamsters are capable of regulating the infection, some worms are capable of surviving the host immune effectors. PMID- 1454424 TI - The use of suckling mice to isolate and grow Giardia from mammalian faecal specimens for genetic analysis. AB - A simple technique is described for preparation of Giardia cysts from faecal samples, the growth of trophozoites in suckling mice and the isolation of trophozoites for genetic analysis by allozyme electrophoresis. In total, 125 new isolates of Giardia have been collected from human and animal sources over a wide geographical area of South Australia and the Northern Territory of Australia. A number of long-established axenized isolates of G. intestinalis belonging to Groups I and II also adapted to grow in suckling mice. These findings indicate that suckling mice are permissive hosts for a variety of genetically dissimilar but morphologically similar organisms of the G. duodenalis type and that this in vivo technique may be less selective than isolation by in vitro culture. The use of suckling mice has revealed that infections can be composed of mixed genotypes and that isolation and purification techniques can be selective. Allozymic interpretation is essential to reveal the genetic complexity of such mixtures. PMID- 1454426 TI - Lectin binding to secretory structures, the cuticle and the surface coat of Toxocara canis infective larvae. AB - Toxocara canis infective larvae are known to produce abundant glycosylated molecules which may be found associated with the surface or secreted into their environment. Using a range of fluorescein-conjugated and gold-conjugated lectins, the localization of particular carbohydrates was defined on the surface of live parasites, and internally at the ultrastructural level. Surface exposure of N acetyl galactosamine and N-acetyl glucosamine was deduced by binding of FITC conjugated Helix pomatia (HPA) and wheat-germ agglutinins (WGA). These sugars appear to be associated with a densely staining surface coat as conventional immuno-electron microscopy procedures dissipate this coat and reveal no surface binding site for these lectins. However, by using cryo-immuno-electron microscopical (C-IEM) techniques, the surface coat is retained and can be shown to bind WGA. The fluorescent lectins also revealed strong WGA binding to the secretory and amphidial pores, while the buccal opening and the cuticular alae bound HPA. Corresponding results were obtained at the ultra-structural level. Thus, HPA bound to the electron-dense area of the cuticle, areas of local cuticular thickening such as the alae and buccal labia, as well as to the oesophageal lumen. WGA also bound to the thickened cuticle of the alae and the buccal opening, but showed no reaction to either the electron-dense layer of the cuticle or the oesophageal lumen. Unlike HPA, WGA did bind specifically to the secretory column contents and the electron-dense regions of the lips associated with the chemosensory amphids. The compartmentalization of the sugars N-acetyl galactosamine and N-acetyl glucosamine, their sources and routes of surface expression and the possible association with the TES glycoprotein antigens are discussed. PMID- 1454425 TI - The relationship between Trichuris trichiura transmission intensity and the age profiles of parasite-specific antibody isotypes in two endemic communities. AB - The present study compares parasite-specific antibody responses in two Caribbean communities with high and low levels of Trichuris trichiura transmission. The age dependency of antibody levels suggest that IgG1 and IgG2 levels relate to the current intensity of infection (as assessed by density of eggs in stool (e.p.g.) and reflect the age-intensity profile at the population level. IgG4, IgE and IgA levels persist into early adulthood and the subsequent decline is gradual. In the low transmission area, lower infection levels are reflected in lower parasite specific antibody levels (of all isotypes) in the community as a whole. Despite a significantly greater past experience of infection in the high transmission area, antibody levels are not maintained at significantly higher levels throughout adulthood. The production of IgA appears to require a threshold for triggering, and a vigorous IgA response is maintained into early adulthood only in the high transmission village where peak intensity is greatest and the age-convexity of intensity is most marked. Experimental and theoretical studies focusing on the dynamic nature of host-helminth interactions in hosts exposed to high and low infection levels, and the putative role of acquired immunity, are discussed in relation to the data presented. PMID- 1454427 TI - Biosynthesis and glycosylation of serine/threonine-rich secreted proteins from Toxocara canis larvae. AB - Toxocara canis infective stage larvae continually produce excretory-secretory (TES) glycoproteins in long-term in vitro culture. The kinetics of synthesis and secretion were studied by metabolic labelling with radioactive [35S]methionine, [14C]serine and [14C]threonine. Maximal incorporation rates required overnight pre-incubation of parasites in medium depleted of the appropriate amino acid. Larvae rapidly incorporated isotope into their somatic tissues, but there was a minimum delay of 10 h before secretion of labelled antigens. Labelling with [14C]serine and [14C]threonine demonstrated a relative abundance of these amino acids in the major surface/secreted glycoproteins of this nematode (TES-32 and 120). Pulse-chase experiments suggested that TES-120 may be derived from a 58 kDa precursor, reflecting extensive posttranslational glycosylation. Inhibition of N glycosylation with tunicamycin and digestion with N-glycanase provided evidence of N-glycosylation in the lower molecular weight ES components (TES-32, 55 and 70). These agents had no effect on the higher molecular weight components (TES 120 and 400) implying that for these molecules glycosylation is predominantly O linked. The largest ES component (TES-400) was unusual, in incorporating serine and threonine but not methionine, and by exhibiting increased apparent molecular weight following pronase digestion; it is suggested that this molecule is a proteoglycan. PMID- 1454428 TI - The secreted and somatic proteinases of the bovine lungworm Dictyocaulus viviparus and their inhibition by antibody from infected and vaccinated animals. AB - Proteinase activities were examined in extracts and excretory-secretory (ES) products of the infective and adult stages of the cattle lungworm, Dictyocaulus viviparus. Multiple enzyme activities were identified from each source, as defined by pH optima, substrate specificities, inhibitor effects and substrate gel electrophoresis. Serine-, cysteine- and metalloproteinases were identified, secreted materials being more active against protein substrates per unit protein than were extracts, and the particular proteinases produced varied with the developmental stage of the parasite. The antigenicity of these parasite proteinases was demonstrated by the inhibition of enzymic activity with Protein G purified serum IgG antibody from both infected and vaccinated hosts and in the retardation of enzyme migration on electrophoresis of enzyme-antibody complexes. For the adult products, this confirmed that the enzymes concerned were of parasite origin, and not host-derived. These results argue for investigation of D. viviparus proteinases as targets for the antibody response in the limitation of parasite-mediated tissue damage and as the active principle behind the anti-D. viviparus vaccine. PMID- 1454429 TI - Effects of testosterone on Heterakis spumosa infections in mice. AB - This study describes the effects of testosterone (Te) on the intestinal nematode Heterakis spumosa in mice. The course of Heterakis infections is apparently under Te-control. At high circulating Te-levels as occurring in intact males, Te treated females, and Te-treated castrated males, the period of release of Heterakis eggs in mouse faeces is greatly extended and the number of eggs released per unit time is markedly elevated in comparison to low Te-levels, as found in untreated females and castrated male mice. Also, the onset of the patent period occurs earlier in Te-treated mice. Testosterone also accelerates development and growth of both female and male worms of Heterakis in mice. Thus, young adult male worms can be observed in the upper colon of Te-treated castrated male mice on day 21 post-infection (p.i.), whereas, at that time, only L4 larvae are present in Te-untreated male castrates. Testosterone also favours the survival of nematodes in hosts. In untreated male castrates, the number of worms present on day 7 p.i. (L2 larvae) is approximately two thirds higher than that found on day 21 p.i. However, such a reduction in the number of worms does not occur in Te-treated castrated mice during the same period of time. The early phases of the life-cycle of Heterakis, i.e. hatching in the small intestine and final settling of L2 larvae in the upper colon are independent of Te. Also, Te does not affect motility and even slightly reduces the fecundity of adult female worms in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454430 TI - Infective endocarditis in children. AB - IE in children is associated primarily with underlying congenital structural heart lesions, predominantly septal defects or complex lesions involving septal defects. During the past 20 years IE associated with rheumatic heart disease has declined to a negligible number. Recently nosocomial catheter-associated bacteremia has been associated with the development of IE, especially in infants. Streptococci are most frequently associated with IE involving natural valves. Although streptococci have also been implicated in cases of IE associated with previous surgery or catheter-related infection, staphylococci, Gram-negative rod species and multiple infecting species are also encountered in this setting. Because infection can often be managed medically, removal of grafts or prosthetic valves is not necessary unless clinical or microbiologic failure occurs. Penicillin with or without an aminoglycoside is the regimen for most community acquired streptococcal IE. A penicillinase-resistant beta-lactam generally is substituted for penicillin in IE caused by an unknown agent and is used in cases of staphylococcal IE. For IE caused by resistant staphylococci, vancomycin is the alternative agent. Currently there is limited information on the efficacy of alternative agents for treating IE caused by enterococci or staphylococci with multiple antibiotic resistance. PMID- 1454431 TI - Outbreak of group A streptococcal infection in a day-care center. AB - During an outbreak of streptococcal infections in a day-care center it is often difficult to determine the source and extent of the outbreak and the optimal means of management. An intervention strategy based on repeated throat cultures and initial antibiotic treatment of culture-positive individuals was used during an outbreak of respiratory tract infections with Group A streptococci at a day care center. The spread of streptococci carriers was studied. Two weeks after the diagnosis of the index case, 61% of the 30 children were colonized with Group A streptococci. From 20 to 30% of the children remained streptococcal carriers, but they did not give rise to secondary cases. Initially the environment was heavily contaminated with Group A streptococci. Damp material might constitute a potential source of streptococcal spread. All Group A streptococcal strains belonged to the same serotype, T12M12. Prompt recognition and intervention are important to prevent spread of streptococcal infection to many day-care attenders. PMID- 1454432 TI - Comparative study of the effectiveness of cefixime and penicillin V for the treatment of streptococcal pharyngitis in children and adolescents. AB - An open label randomized trial conducted in rural Kentucky compared the efficacy and safety of cefixime (CFX), 8 mg/kg once daily, with those of penicillin V (PEN), 250 mg 3 times daily, in 110 pediatric patients with Group A beta hemolytic streptococcal pharyngitis. Forty-eight CFX and 47 PEN patients were evaluable for efficacy. At the end of therapy bacteriologic eradication was 45 of 48 (94%) and 36 of 47 (77%) in the CFX and PEN V groups, respectively (P < 0.05). Up to 6 weeks posttherapy 10 (21%) CFX patients and 21 (45%) PEN patients had positive Group A beta-hemolytic Streptococcus cultures (P < 0.05). Concordant serotypes were identified from 4 of 7 CFX and 15 of 17 PEN patients with positive repeat cultures. All discordant serotypes (5 of 31) were identified at greater than 19 days posttherapy. Symptomatic treatment failures (concordant serotypes) occurred in 1 (2%) CFX and 8 (17%) PEN patients (P < 0.05). Drug-related adverse experiences consisted of 2 cases of mild diarrhea and loose stools in the CFX group and none in the PEN group. No clinically significant laboratory test abnormalities occurred in either group. CFX, once daily, was as safe as and significantly more effective than PEN given 3 times daily for the treatment of Group A beta-hemolytic streptococcal pharyngitis. PMID- 1454433 TI - Oral ciprofloxacin in the management of chronic suppurative otitis media without cholesteatoma in children: preliminary experience in 21 children. AB - The current medical management of children with chronic suppurative otitis media without cholesteatoma unresponsive to local treatment and oral antibiotics is intravenous antibiotic therapy in the hospital setting. We studied the efficacy and toxicity of oral ciprofloxacin in chronic suppurative otitis media. Twenty one children received oral ciprofloxacin, 30 mg/kg/day. Ear discharge was positive for bacteria resistant to other oral medications and susceptible to the quinolones. The mean duration of treatment was 16.7 days. In 18 children suppuration ceased and 3 failed their first course. During a mean follow-up of 15.4 months, 6 children remained free of ear, nose and throat problems. Otorrhea recurred in 12 children. Ear cultures were positive for organisms susceptible to amoxicillin in 5 of them. In 7 cases Pseudomonas aeruginosa was again isolated from otorrhea. Repeated antibiotic therapy was advocated only in 3 (2 responded to ciprofloxacin; 1 failed ciprofloxacin and was cured by ceftazidime). Adverse clinical effects were not observed. Transient neutropenia was observed in 1 child. There was no change in the height percentile. The results of this study show that children with chronic suppurative otitis media without cholesteatoma can be effectively treated with oral ciprofloxacin. This novel approach may prevent hospitalization. PMID- 1454434 TI - Safety and immunogenicity of acellular pertussis vaccine, combined with diphtheria and tetanus as the Japanese commercial Takeda vaccine, compared with the Takeda acellular pertussis component combined with Lederle's diphtheria and tetanus toxoids in two-, four- and six-month-old infants. AB - A double blind, randomized, controlled trial compared the safety and immunogenicity of an acellular pertussis vaccine formulated at Lederle using the Takeda acellular pertussis component combined with Lederle diphtheria and tetanus toxoids vaccines (APDT), with the commercially available Japanese Takeda vaccine (APDT-T/J) as a three-dose series to 2-, 4-, and 6-month-old children. Sera were analyzed for antibody to pertussis antigens: lymphocytosis-promoting factor; filamentous hemagglutinin; 69-kDa outer membrane protein; pertussis agglutinogens; neutralizing antibodies to LPF; and to diphtheria and tetanus toxoids. Information concerning local reactions and systemic events were collected daily for 10 days postimmunization. The overall reaction rate was low for both groups. There were no reactions that contraindicated subsequent vaccine and no serious adverse events. For local reactions statistically significant differences between the groups were seen only for a greater incidence of induration in the APDT group at 2 months (12% vs. 0%, P < 0.01), and at 4 months (8% vs. 0%, P = 0.4) compared to the APDT-T/J group. Of the few systemic reactions the only statistically significant difference between the vaccine groups was a greater incidence of fretfulness in the APDT group after the initial immunization (12% vs. 2%, P = 0.05). There were no statistically significant differences in the immune response between the two vaccines at the 7-month visit. We conclude that APDT is equivalent to the commercially available Takeda vaccine (APDT-T/J). PMID- 1454435 TI - Relatedness of strains of methicillin-resistant coagulase-negative Staphylococcus colonizing hospital personnel and producing bacteremias in a neonatal intensive care unit. AB - The emergence of methicillin-resistant coagulase-negative Staphylococcus as a major bacterial pathogen in neonatal intensive care units has stimulated interest in the epidemiology of spread of the organism. During a 12-month "epidemic" of bacteremias with methicillin-resistant coagulase-negative Staphylococcus we compared the characteristics of bacteremic and personnel nasally-carried strains by traditional and biomolecular methods. Sixty-two percent of neonatal intensive care unit nurses were colonized with methicillin-resistant coagulase-negative Staphylococcus with similar speciation to bacteremic strains. Inspection of plasmid profiles revealed a moderate degree of similarity between bacteremic and colonizing strains although genomic DNA restriction patterns showed diversity. Ribotype patterns were highly conserved (90%) in personnel strains. A 2.6 kilobase plasmid DNA probe hybridized to similarly sized plasmids and larger plasmids in one-half of the strains. We hypothesize that related methicillin resistant strains may be transferred among personnel and neonates in the neonatal intensive care unit. Epidemiologic studies of coagulase-negative staphylococci should consider multiple molecular techniques to relate strains. PMID- 1454437 TI - Epidemiology of adult sexually transmitted disease agents in children being evaluated for sexual abuse. AB - This prospective study describes the epidemiology of adult sexually transmitted disease agents in 1538 children ages 1 to 12 years being evaluated for possible sexual abuse. Infections with these agents were related to the presence or absence of a history of sexual contact. Neisseria gonorrhoeae (GC) was found in 2.8% (41 of 1469); human papillomavirus presenting as condyloma acuminata, 1.8%; Chlamydia trachomatis, 1.2% (17 of 1473); Treponema pallidum (syphilis), 0.1% (1 of 1263); and herpes simplex virus, 0.1%. Overall a history of sexual contact was present in 83% of children with N. gonorrhoeae; condyloma acuminata, 43%; Chlamydia trachomatis, 94%; syphilis, 0%; and herpes simplex virus, 50%. Selected vaginal discharges were examined for Trichomonas vaginalis and bacterial vaginosis. In children comprehending questions regarding sexual contact (i.e. were "verbal"), 89% with N. gonorrhoeae, 100% with Chlamydia trachomatis and 63% with condyloma acuminata had a history of sexual contact, indicating that in "verbal" children any infection with N. gonorrhoeae or C. trachomatis was highly associated with sexual contact. PMID- 1454436 TI - Perinatally acquired human immunodeficiency virus infection: extent of clinical recognition in a population-based cohort. Massachusetts Pediatric HIV Surveillance Working Group. AB - To evaluate factors that may affect the timely diagnosis of children with human immunodeficiency virus (HIV) infection, we compared data derived from two population-based pediatric HIV studies. Data from anonymous newborn HIV serosurveys were used to estimate the number of children born to HIV-seropositive mothers. A statewide active surveillance project determined the number of HIV exposed children who had been clinically recognized. Of 88,732 Massachusetts newborn specimens tested anonymously for HIV antibodies during a 12-month period (November, 1987, to October, 1988), 223 were positive. As of October, 1991, 78 of these children (35%) had been identified by a statewide network of infectious disease physicians. HIV-exposed children born in inner city hospitals were more likely to have come to medical attention than those born in suburban hospitals (47% vs. 17%). Among the 29 children with confirmed HIV infection (13% of 223), the initial evaluation for HIV occurred at an earlier age among children born in inner city hospitals than among children born in other areas. HIV testing practices that rely heavily on risk assessment may result in delayed diagnosis of HIV infection in children whose mothers are not perceived to be at risk. PMID- 1454438 TI - Mycobacterium tuberculosis in children with human immunodeficiency virus type 1 infection. AB - A retrospective study was conducted at the Childrens Hospital Center at Jackson Memorial Hospital in Miami, FL, to evaluate the natural history of Mycobacterium tuberculosis infection in nine children with vertically acquired human immunodeficiency virus type 1 infection. The patients' ages ranged from 6 months to 7 years (median age, 42 months). Common presenting symptoms included prolonged fever, cough and anorexia. Only one patient had a positive tuberculin test. Five patients evidenced only pulmonary disease, three patients had pulmonary and extrapulmonary disease and one patient developed extrapulmonary tuberculosis (mastoiditis) and pulmonary interstitial disease that could not be attributed to mycobacterial infection because of lack of information. Organisms isolated before January, 1989, were susceptible to isoniazid and rifampin whereas isolates from three patients cultured after that time were resistant to multiple antituberculosis drugs. The median survival time after M. tuberculosis diagnosis for all children was 20 months. Our study suggests that children with human immunodeficiency virus type 1 infection who have tuberculosis have an increased risk for extrapulmonary disease. A high index of suspicion for the diagnosis of M. tuberculosis should be maintained in human immunodeficiency virus type 1 infected children with prolonged fever and respiratory symptoms. In areas of high endemicity of multidrug-resistant organisms, therapy with a broader panel of drugs may need to be instituted until susceptibility testing becomes available. PMID- 1454439 TI - Rubella among the Amish: resurgent disease in a highly susceptible community. AB - Although the Amish make up less than 0.05% of the United States population, nearly all rubella reported in the United States in 1991 occurred in this population. In early 1991 a large rubella outbreak in a Tennessee Amish community that had experienced no rubella for 17 years afforded an opportunity to describe the epidemiology of rubella in this unique population. Structured interviews were conducted with 54 Amish families. Of 383 persons in the sample 85 (22%) had rubella. Illnesses were mild; 16% of cases lacked fever and 20% of cases reported no symptoms except rash. Children < 17 years of age were 7 times more likely than older individuals to be affected (77 of 214 vs. 8 of 165). All pregnant women in the community were > 20 years of age; none developed rubella. No congenital rubella syndrome was recognized. Although rubella is increasingly a disease of adolescents and young adults, in this outbreak, rubella was again a childhood disease. Illness in this community-based investigation was mild; rubella may be difficult to diagnose and report. Immunity after remote natural infection was durable since the community's last outbreak. Pregnant women probably were protected by the age distribution of immunity; this age distribution may not occur in other Amish populations. If preventable morbidity from rubella and other vaccine preventable diseases is to be avoided in this group, increased attention should be directed to encouraging vaccinations among Amish persons. PMID- 1454440 TI - Disseminated Mycobacterium avium complex in non-human immunodeficiency virus infected pediatric patients. PMID- 1454441 TI - Disseminated fusariosis involving bone in an adolescent with leukemia. PMID- 1454442 TI - Anaerobic meningitis in children: case report and review of the literature. PMID- 1454443 TI - High prevalence of Chlamydia pneumoniae infection in children and young adults in Spain. PMID- 1454444 TI - Gonorrhea in children: epidemiologic unit analysis. PMID- 1454445 TI - Resumption of breast-feeding in later childhood: a risk factor for mother to child human immunodeficiency virus type 1 transmission. PMID- 1454446 TI - Comparative study of cefprozil and cefaclor in children with bacterial infections of skin and skin structures. PMID- 1454447 TI - Effect of tip size on acoustic reflectometry. PMID- 1454448 TI - Comparative efficacy of mecillinam, mecillinam/amoxicillin and trimethoprim sulfamethoxazole for treatment of typhoid fever in children. PMID- 1454449 TI - Newborn with hydrops and a rash. PMID- 1454450 TI - Enteroviral meningitis in infants. PMID- 1454451 TI - Characteristics of group A streptococci isolated from children with nonsuppurative complications or severe infection in Japan. PMID- 1454452 TI - Randomized controlled trial of steroids in pertussis. PMID- 1454453 TI - Syringe problems with hepatitis B vaccine. PMID- 1454454 TI - Newborn sepsis caused by Streptococcus pneumoniae. PMID- 1454455 TI - Recommendations for intravenous immunoglobulin therapy of Kawasaki disease. PMID- 1454456 TI - Neuropsychological correlates for realism-abstraction, a dimension of aesthetics. AB - 240 undergraduates were shown 50 color slides of paintings representing ten areas of subject matter and five levels of realism. The subjects rated from 1 to 9 their liking of each painting and then took the Cognitive Laterality Battery. Individuals with clear preference for realism formed one group and those showing clear preference for abstraction formed a second. A multivariate analysis of variance for subjects' Cognitive Laterality Battery scores showed a significant interaction, which may be interpreted as supporting the idea that there is a possible neuropsychological basis for the realism-abstraction preference dimension in aesthetics. PMID- 1454457 TI - Parsing attentional components during a simple reaction time task using sleep deprivation and amphetamine intervention. AB - To examine the independent contributions of the attentional components of arousal and activation in performance, sleep deprivation was used as the attentional manipulation in a reaction time (RT) task. The subjects were 18 men who underwent 63 hr. of sleep deprivation during which time they periodically performed a simple auditory RT task with manipulations of temporal uncertainty and intensity. After 48 hr. sleep deprivation, subjects ingested either 20 mg d-amphetamine or placebo, then continued testing throughout Day 3. During sleep deprivation, performance was more impaired on trials associated with low temporal uncertainty (arousal) and high preparation (activation) than on trials associated with high temporal uncertainty and low preparation. Analysis indicated that sleep deprivation perturbed activation, leaving arousal relatively unimpaired and that amphetamine had a restorative effect on the sleep deprivation-impaired activation system. The stimulus of high intensity was disruptive on Day 1 but facilitative on Day 3, a result which was interpreted as an initial inhibition, then disinhibition of arousal. Results were interpreted to indicate that, in some instances, alterations in the less specific arousal and activation systems may underlie impairment or changes in the more specific information processing and motor output stages. PMID- 1454458 TI - Human figure drawings as estimates of intelligence for adolescents in an inpatient psychiatric unit. PMID- 1454459 TI - Stimulus-dependent ear asymmetry in a dichotic monitoring task. AB - Auditory lateralization was investigated in 26 right-handed and 26 left-handed, normal subjects using two dichotic monitoring tasks in each proband [dichotic consonant-vowel (CV) syllable monitoring once with the syllable /ta/ and once with the syllable /da/ as target]. Subjects were instructed to monitor for the presence of a target CV which could occur in either ear. They responded by depressing a response button; reaction time (RT) and hit rates were recorded. In right-handers the syllable /ta/ presented to the right ear was detected more frequently, on the average, than presented to the left ear. Also, RT was shorter for detection of /ta/ in the right ear than for detection in the left ear for both right- and left-handers. The detection of /da/ showed no ear advantage in hit rate and RT either for right-handers or for left-handers. These results demonstrate the existence of a right-ear advantage in dichotic monitoring of the target syllable /ta/ but not for the target syllable /da/. This difference in evoking a right-ear advantage is attributed to a difference in the difficulty of detection of both targets. It is argued that the detection of /da/ is too difficult to evoke phonetic processing, leading to a right-ear advantage. PMID- 1454460 TI - Changes in body consciousness relate to regularity of exercise training. AB - Previous work has indicated improvement for scores on self-reported measures of body consciousness as aerobic fitness increased. To test whether exercise sufficient to improve aerobic fitness must be sustained on a regular basis to achieve positive changes in body consciousness, two separate periods of exercise training of 2 or 3 weeks duration were completed by nine female volunteers. The two exercise sessions were separated by 10 days of no exercise. Five women, as controls, did not exercise. Despite significant physiological improvement in the exercisers, no changes in self-perceived body self-consciousness were observed. Such changes may depend on the maintenance of a regular exercise regimen or the magnitude of physiological improvement. PMID- 1454461 TI - Visuomotor organization in the left-handed child: a neuropsychological approach. AB - In this study we used the Rey-Osterrieth complex figure to examine the visuomotor organization of 514 boys and girls, aged 5.5 to 20.5 yr. All were left-handed as judged by the Edinburgh Handedness Inventory. Statistical evaluation showed significant differences in teh visuomotor organization for boys and girls across the various age groups. Statistically significant differences also appeared between the two sexes at the age groups 7.5 to 8.5 and 8.5 to 9.5, with girls showing better organization than boys. PMID- 1454462 TI - Factors contributing to perception of health in young black women. AB - An exploratory descriptive design using interviews and open-ended questions examined factors which were associated with perceptions of health held by 22 young black women, ages 18 to 40 years. Interview findings indicated that, among these women, obesity was considered to contribute positively to perceptions of health as did eating good foods and engaging in stress-reducing activities. PMID- 1454463 TI - Where does an anorthoscopic image appear? AB - Two experiments were performed to examine where anorthoscopic images appear. In Exp. 1, in which a narrow slit was used, the images were seen as spatially compressed, but also as spatially displaced along each direction of movement even when two patterns were moved simultaneously and in different directions. These results are incompatible with the retinal painting hypothesis. In Exp. 2, in which a wider slit was used, anorthoscopic images appeared immediately after a pattern entered and left the slit. The two images were considered to depend on temporal changes of parts of a pattern passing across left and right edges of the slit, respectively. PMID- 1454464 TI - Differentiation of Alzheimer and cerebrovascular patients with the Minnesota Percepto-Diagnostic Test--Revised. AB - 60 adult patients with focal cerebrovascular accidents (30 with left cerebral hemisphere lesions, 30 with right cerebral lesions) and 30 adults with Alzheimer disease were compared to 30 normal adults on the Minnesota Percepto-Diagnostic Test--Revised (MPD--R). The regular scoring variables plus the two-step method of diagnosis for brain damage with the MPD--R were used. One-way analyses of variance with age and mental status as covariates yielded a significant difference between control subjects and brain-damaged patients on most of the MPD -R variables. The controls scored the best, followed by the Alzheimer and cerebrovascular groups. Planned comparisons for cerebrovascular vs Alzheimer subjects were significant across all MPD--R scores except distortion of dots; the Alzheimer subjects scored better than the cerebrovascular subjects. The two cerebrovascular groups were not differentiated by the MPD--R scoring variables. The MPD--R correctly identified 96% of each of the two brain-damaged groups and 70% of the control group. Findings are described in terms of the utility of the MPD--R in differential diagnosis with elderly populations. PMID- 1454465 TI - Relationship between psychomotor functioning and health status among elderly persons? AB - 45 older adults were tested twice per year for three years in a 9 (psychomotor) by 30 (health status, well-being) matrix of variables. That only 84 significant correlations were found suggests no relationship between psychomotor performance and health status. PMID- 1454466 TI - Perceived clothing deprivation: further evidence. AB - The purpose of this study was to extend the conceptualization of perceived clothing deprivation among three groups of adolescents: 161 skateboarders, 61 baseball players, and 336 general high school students. Perceived clothing deprivation, the dependent variable, was measured by two previously developed scales, Inability to Buy and Clothing Deprivation Relative to Peers. Regression analysis of self-reported economic stress indicated that the combination of lower income and increased demand was positively related to both clothing deprivation factors. Group membership was not significantly associated with Inability to Buy but was with Clothing Deprivation Relative to Peers. Both male sports groups reported greater perceived dissatisfaction than the general population of high school students. These results support the idea that perceived clothing deprivation is self-defined and peer-dependent among adolescents and support the proposition that clothing deprivation reflects primarily influence of dynamic rather than stable variables. PMID- 1454467 TI - Comparison of empirically derived and predicted standard scores for Form II of the Luria-Nebraska Neuropsychological Battery. AB - Until Wong, Schefft, and Moses published norms for Form II of the Luria-Nebraska Neuropsychological Battery in 1990, Golden, Purisch, and Hammeke's 1985 regression equations were the only procedure available to interpret scores on Form II of the battery. In the present study comparison of the empirically based norms with standard scores obtained via the regression equations showed that (1) the scale means and standard deviations used in the development of the regression equations indicated substantially more impairment than those obtained by Wong, et al. and (2) the standard (T) scores predicted by the regression equations consistently underestimated impairment relative to the T scores obtained directly from Wong, et al.'s empirically derived norms. Reasons for, and implications of, these findings were discussed. PMID- 1454468 TI - Responses of conduct-disordered versus psychotic adolescents to PPVT-R items of human versus nonhuman content. AB - 24 conduct-disordered youth were compared with 22 psychotic youth on differential responsivity to human versus nonhuman content plates on the PPVT-R. Conduct disordered youth performed worse on items featuring human stimuli, implying antisocial patterns which might correlate with more active avoidance of social relating. PMID- 1454469 TI - Strategies for object identification and confidence: influence of appearance, amount of context, and familiarity. AB - In an experimental study of the everyday, what-is-this? perceptual encounter, the strategies subjects used to identify a focal object were influenced by the object's physical appearance, the amount of context in which it was displayed, and subjects' familiarity with the object. These factors also affected subjects' confidence in the accuracy of their identifications. The results appear to support the contention that visual processing is a middle-out rather than either a top-down or bottom-up sequence. PMID- 1454470 TI - The incidence of sleep problems among type A and type B college students: changes over a ten-year period (1982-1992). AB - Ten years ago we reported that Type A scoring students were twice as likely as their Type B peers to report sleep problems. In an exact 1992 replication of that study, no Type A-B differences in the frequency of self-reported sleep problems were observed; however, the over-all incidence of sleep problems among the 753 college students had increased substantially. PMID- 1454471 TI - Abnormalities of psychomotor development in schizophrenia: a rehabilitation perspective. AB - This study was an evaluation of the psychomotor profiles of 22 schizophrenic patients, investigated by means of a test battery developed for the assessment of psychomotor profiles of 10- to 12-year-old children. Analysis indicates that abnormal psychomotor development is an inherent feature of the disease and probably is antecedent to a full psychopathological picture. PMID- 1454472 TI - Arousability and eating problems of college women. PMID- 1454473 TI - Conditioning reaction time: evidence for a process of conditioned automatization. AB - The classical conditioning of the standard, simple reaction time (RT) in 140 college men and women is described. Consequent to an anticipatory instructed conditioning procedure, two experimental and two control groups acquired voluntary, controlled US(light)-URTR (unconditioned reaction-time response) associations which then served as the foundation for subsequent classical conditioning when a novel CS (auditory click) was simultaneously paired with the US. Conditioned reaction-time responses (CRTRs) occurred significantly more often during test trials in the two experimental groups than in the two control groups. Statistical and introspective findings support the notion that observed CRTRs may be products of cognitively unconscious conditioned automatization whereby the conditioning of relatively slow, voluntary, and controlled US-URTR associations leads to the acquisition of relatively fast, involuntary, and automatic CS-CRTR associations. PMID- 1454474 TI - Computer measurement of the autokinetic effect. AB - Previous methods for measurement of the autokinetic effect have several drawbacks, including limited accuracy and limited information. A new computer technique for measurement of the autokinetic effect is presented. A computer and computer mouse record tracing movements every tenth of a second, yielding a permanent record that can be analyzed further. The method is flexible, sensitive, and stable, as shown by test-retest correlations using 26 subjects. Correlations and medians for latency, total distance traveled, number of stops, straight line distance from origin to end-point, maximum speed, maximum acceleration, percent of time in motion, and speed and percent of motion in each of eight compass directions were computed. The results are similar to previously reported values. PMID- 1454475 TI - Effect of using age-adjusted suicide rates on time-series studies of the American suicide rate. PMID- 1454476 TI - Personal determinants of leisure-time exercise activities. AB - This study investigated the importance of personal determinants such as self efficacy, beliefs about the contribution of exercise, health locus of control, and dispositional optimism for leisure-time exercise in a working population. The main predictors of such exercise were beliefs and self-efficacy with the generalization of the latter to eat correctly. Beliefs and efficacy expectations were highly correlated. Neither health locus of control nor dispositional optimism was related to leisure-time exercise; however, optimism was related to the positive belief that exercise contributes to health. Ramifications of the findings were carefully described. PMID- 1454477 TI - Self-monitoring and identification of olfactory dimensions. AB - The basic categories of odors are not agreed on. Many classifications of odors have been proposed, but none has met widespread acceptance. The variability among qualitative judgments of odors which makes it difficult to construct reliable classifications may depend on cultural or personal idiosyncrasies. To check personality factors in odor evaluation, we asked 40 subjects, who had previously completed a personality questionnaire, to make qualitative judgments about 10 odors on 10 semantic differential scales. From comparison of two different self monitoring groups, on the semantic differential, reliable differences did not emerge. While high self-monitoring subjects tended to maintain intermediate positions, for some odors, low self-monitors hazarded more polarized evaluations. PMID- 1454478 TI - Arousability and bruxism in male and female college students. AB - The relationship between arousability, as measured by the Arousal Predisposition Scale, and bruxism was computed for groups of 41 male and 75 female university undergraduates as a further test of the hypothesis that bruxism is a stress linked disorder. Contrary to our prediction, arousability was not related to bruxism in men and the relationship between these variables for women was significant but relatively weak. When considered with other studies, these data provide a clearer focus for further study of the stress-bruxism hypothesis. PMID- 1454479 TI - Reporting what you have seen: effects associated with age and mode of questioning on eyewitness reports. AB - This study examined age-related differences in the reporting of a filmed domestic scene, in which a mother was either ambiguously caring or ambiguously abusive toward her daughter. Three age groups were used (3- to 4-yr.-old, 6- to 7-yr. old, and adult), and three modes of questioning were used (free recall, short answer cued-recall, and leading questions either consistent or inconsistent with what was observed). There were 119 subjects in all: 39 3- to 4-yr.-olds, 39 6- to 7-yr.-olds, and 41 adults. Developmental trends were found in the subjects' ability to answer free-recall questions and cued-recall questions. Although 6- to 7-yr.-olds were significantly lower than adults in their accuracy scores on the cued-recall questions, they were still highly accurate. There were also significant age-related differences in the subjects' suggestibility, with the 3- to 4-yr.-olds being relatively suggestible, the 6- to 7-yr.-olds less so, and the adults virtually unsuggestible. When the leading questions that concerned the central theme of the film (i.e., Was the mother abusive or not?) were isolated, however, no significant age-related differences in suggestibility were found. PMID- 1454480 TI - Health-related physical fitness levels of elementary school children ages 5-9. AB - National health goals include an increase in the physical activity and physical fitness of school-age children by the year 2000. To assess current fitness levels in the state of Maine, more than 8,000 public school students, ages five through nine, were assessed using a nationally known (American Alliance for Health, Physical Education, Recreation and Dance) health-related physical fitness test. Maine students were then compared with a national norm group on (1) the one-mile walk/run (minutes:seconds), (2) skinfold thickness (centimeters), (3) one-minute timed sit-ups (number performed correctly), and (4) the sit and reach test for flexibility (centimeters). Generally, Maine boys and girls scored higher than the norms on the sit-up, sit and reach, and one-mile walk/run; however, they had significantly larger skinfold thicknesses. Implications for assessment of health related fitness in this age group were discussed. PMID- 1454481 TI - The moon illusion: a different view through the legs. AB - The fact that the overestimation of the horizon moon is reduced when individuals bend over and view it through their legs has been used as support for theories of the moon illusion based upon angle of regard and vestibular inputs. Inversion of the visual scene, however, can also reduce the salience of depth cue, so illusion reduction might be consistent with size constancy explanations. A sample of 70 subjects viewed normal and inverted pictorial arrays. The moon illusion was reduced in the inverted arrays, suggesting that the "through the legs" reduction of the moon illusion may reflect the alteration in perceived depth associated with scene inversion rather than angle of regard or vestibular effects. PMID- 1454482 TI - An appraisal of body image among Nigerian university students. AB - This study was designed to provide baseline data on the attitudes of Nigerian university students toward their own bodies. 286 students completed the 25-item version of the Body Cathexis Scale of Berscheid, et al. These students were more satisfied than they were dissatisfied with their body parts. The body weight and general muscle development were aspects with which they were most dissatisfied. Compared to men, women were significantly more satisfied with their ears, body weight, general muscle development, chest/breast, size of sex organs, and appearance of sex organs. These baseline data may help screen Nigerian university students with negative body ideation. PMID- 1454483 TI - Cognitive and somatic state anxiety and self-confidence in cheerleading competition. AB - 77 cheerleaders participating in a national collegiate championship competition were administered the Competitive State Anxiety Inventory-2 immediately prior to performance. Significant correlations were found between cognitive and somatic state anxiety, a finding consistent with previous research. Negative correlations were found between both cognitive and somatic anxiety and self-confidence, also as previously reported. Canonical discriminant analysis indicated that significant discrimination between the teams could be accomplished by a combination of the state-anxiety variables. Both groups, 36 men and 41 women, differed significantly from normative scores on the somatic subscale. PMID- 1454484 TI - Responses of first-grade children to concepts about printed material before and after shared reading experiences. AB - A study was conducted to investigate the effects of shared reading experiences using books with predictable content to assess 24 inner-city African-American first-graders' concepts about printed material. The 8-week treatment using a two group pre- and posttest experimental design with random assignment showed no significant differences between groups. A larger sample and longer treatment time are recommended for replicating this study. PMID- 1454485 TI - The correlation between reaction time and the ponderal index. PMID- 1454486 TI - Maximized split-half reliabilities and distributional characteristics for Harris Lingoes subscales with few items: a reevaluation for the MMPI-2. AB - 100 MMPI-2 protocols were obtained from the files of an outpatient clinic. Distributions of all possible split-half combinations were computed for selected Harris-Lingoes subscales with few items. As expected, max r reliability estimates were significantly greater than alpha estimates and distributions of correlations were negatively skewed. Inspection of the distributions suggested that the Amorality scale contains an ambiguous item which does not appear to belong in this grouping. Serious problems were noted with the Hy5 subscale. Alpha reliabilities were comparable to previously reported estimates, and max r reliability estimates closely resembled reported test-retest estimates. PMID- 1454487 TI - Which handedness: preference or performance? AB - Two ways of measuring handedness, questionnaires and hand-efficiency tests, are compared. A method for combining performance scores of 128 children from different hand-efficiency tests to obtain a single handedness score based on efficiency is presented. Handedness classifications according to different thresholds of preference as well as of performance are shown. To select pure right- or left-handers, it is argued that handedness should be established simultaneously through preference questionnaires and performance tests and that only subjects falling simultaneously into the same category on both measures be kept. Advantages and disadvantages of each classification are discussed as well as the relations between efficiency and motor control of upper limb and hand. PMID- 1454488 TI - Relationship between dietary components and aspects of sleep. AB - To test the hypothesis that major dietary constituents are related to quantity or quality of sleep, 27 adult volunteers participated in a five-day study. Subjects completed detailed dietary logs each day, and each morning completed the St. Mary's Hospital Sleep Questionnaire. Dietary data were converted to seven major nutritional constituents and these were averaged over the 5-day period. None of the 98 correlations between diet and sleep were significant. These findings provide no support for a link between sleep and diet in adults. PMID- 1454489 TI - An exploratory examination of the Parent-initiated Motivational Climate Questionnaire. AB - The purpose of this study was to examine the factor structure and internal reliability of the Parent-initiated Motivational Climate Questionnaire among 112 boys and 98 girls, young adolescents, and older adolescents. The questionnaire had a meaningful 3-factor structure and showed acceptable internal reliability. There was a significant difference between how boys and girls perceived their parents' reactions to their learning new physical skills. In contrast to boys, girls thought that both their mothers and fathers focused on improvement and self satisfaction during the learning process and deemphasized learning without effort and worrying about making mistakes. Age did not significantly affect the perceptions the individuals had of their parents' convictions about their learning in the physical domain. PMID- 1454490 TI - Comparison of frame size and body mass index methods of assessment in the study of blood lipids. AB - This study compared frame size and body mass index methods of assessment in relation to blood lipid levels. The data were obtained from the records of 84 men and 193 women who voluntarily participated in health fairs held at two suburban hospitals. Significant relationships and differences were found between the anthropometric and lipid variables studied. The two methods of classification denoted moderate association and reflected some divergence in classification between them. PMID- 1454491 TI - Distance perception in the spiny mouse Acomys cahirinus: vertical jumping. AB - Acomys cahirinus, a precocial muroid, that has shown precise jumping in the natural habitat, did not jump from 25 cm in a laboratory situation. To investigate this further, A. cahirinus were observed jumping from platforms at two different heights, onto different sized checkered substrates and from a visual cliff. Adult animals discriminated between platforms that were 6.4 cm and 25.4 cm above the substrate and between small and large checkered patterns on the floor. Most adult animals and neonates jumped down on the shallow side of the visual cliff. Animals developed individual patterns of jumping over a series of trials, with some jumping often, some rarely, and others jumping only from the low platform. Good distance perception was indicated when they did not jump from heights, and by their making appropriate postural adjustment when they did jump from heights and landed without mishap. Different spacing of trials indicated that height was a more effective stimulus for animals which had all four conditions on the same day, while floor pattern was more effective for animals with each of the four conditions on a separate day. PMID- 1454492 TI - Is the Benussi effect a kinetic depth effect? AB - Rapid, successive presentations of an eccentric circle pattern and its mirror image elicited apparent depth and, as has been previously demonstrated for the Benussi effect, there was an increase in apparent depth with an increase in circle eccentricity. Taken together, these data were interpreted as contravening Wallach, Adams, and Weisz's account of the Benussi effect as an instance of the kinetic depth effect. PMID- 1454493 TI - Relative right temporal-lobe theta activity correlates with Vingiano's hemispheric quotient and the "sensed presence". AB - Measures of monopolar alpha and theta rhythm activity over the left and right temporal lobes were correlated with the subjects' hemisphericity (Vingiano) scores, temporal lobe signs, and concurrent subjective experiences during partial sensory deprivation. There was a positive association (rho = .49) between the scores for right hemisphericity and the relative amount of right/left theta rhythm but not right/left alpha rhythm activity. Significant intercorrelations between right hemisphericity, an history of ego-alien intrusions and experiences of a sensed presence, "detachment from the body," and fear during the recordings were noted. These results support the hypothesis that this class of mystical experiences is encouraged by hemispheric mismatch in temporal-lobe theta activity. PMID- 1454494 TI - Arousing patriotic feelings in men and women. PMID- 1454495 TI - Mathematical performance before, during, and following cycling at workloads of low and moderate intensity. AB - Mental arithmetic performance before, during, and following low (40% maximal heart-rate reserve; approximately 90 watts exercise for 15 min.) and moderate (60% maximal heart-rate reserve; approximately 150 watts exercise for 10 min.) intensity cycling by 20 male students (M age = 28.1 yr.) was studied. Subjects were grouped, by using a median-split on their total mathematical performance scores, into a group of 10 low in arithmetic skill and a group of 10 high in arithmetic skill. The numbers and percentages of right answers to 1-min. mathematical problem-sets of either group were not different in the various conditions, suggesting that 25 min. of progressive cycling exercise did not influence mathematical problem-solving efficacy. PMID- 1454496 TI - Spatial localization and auditory lateralization: binaural cues and their absence. AB - In 1990 Cheatham suggested there might be a right-ear advantage for the perception of speech and music for right-handed individuals, which confirms Kinsbourne's observation of a general right-ear advantage. These findings, however, contrast with Segalowitz and Plantery's work that supports attentional bias in lateralized processing of these stimuli. The attentional bias model has also been criticized by Bryden on the basis of its circularity. At present there has not been sufficient evidence to settle this debate empirically. The author suggests that the controversy may best be resolved by disentangling the folklore surrounding spatial localization and auditory lateralization to reexamine this field in light of recent empirical findings by Bryden and by Porac, Coren, and Duncan, who inferred an inherent rightward bias to many kinds of stimulation, including auditory, in right-handed individuals. The present focus is that Cheatham's 1990 data lend themselves more readily to the rightward bias that occurs in right-handed subjects and not to previous structural or attentional models. PMID- 1454497 TI - Mirror training in three dimensions for dental students. AB - Dental students have significantly improved skills of indirect vision following mirror exercises in two dimensions. The objective of this study was to assess whether freshmen improved these skills after mirror training in three dimensions. A pretest was given to 60 subjects, maneuvering a handpiece-shaped probe through a brass block maze. Total time, error time, and total errors were recorded for each of three perceptually different mirror positions. Subjects were then randomly divided into two groups. Group A participated in 2 training sessions; Group B (a control) received no training. Both groups then performed a posttest. Transformed time scores examined by analysis of variance indicated a significant difference for total time between Groups A and B at posttest at each mirror position. For error time, Groups A and B were significantly different at posttest at Positions 2 and 3. For total errors, groups were significantly different at posttest at Mirror Position 3 only. Indirect vision skills improved significantly with training in three dimensions. PMID- 1454498 TI - Effects of disability labels on teachers' perceptions of students' self determination. PMID- 1454499 TI - The relationship between turning behavior and motoric dominance in humans. AB - This study attempted to correlate turning direction on the stepping test with three measures of motoric dominance--handedness, footedness, and eyedness. 111 high school students performed the stepping test while deprived of visual and auditory cues during a 1-min. interval. Although only slightly more than half of the subjects rotated rightward, the direction and magnitude of turning correlated significantly with footedness and eyedness but not with handedness. Thus, axial turning biases and motoric dominance may partially share a common mechanism, possibly involving vestibular asymmetry. PMID- 1454500 TI - Self-esteem and narcissism among the most and least empathetic Finnish baseball players. AB - 560 girls and 819 boys, ages 8 to 16 years and actively interested in Finnish baseball, were tested in small groups in three training-camp championship games with the modified Mehrabian and Epstein's Empathy Scale, and the Battle Self esteem Inventory, Form B. Narcissism was estimated on the 1984 Emmons scale. The hypothesis that the most empathetic players compared with the least empathetic players have better self-esteem and less narcissism was confirmed. PMID- 1454501 TI - Some concluding thoughts on the debate about the Vividness of Visual Imagery Questionnaire. AB - The case for the validity of the Vividness of Visual Imagery Questionnaire is examined. It is argued that the validity of the questionnaire is not established in the literature and that paradigmatic and conceptual ambiguity militate against a clear understanding of that literature. Phenomenological problems with questionnaire reports such as the use of untrained introspectors and the preponderance of exaggerated self-reports of prowess at imagery are discussed. The conditions needed for inter-and intrapsychic validity are delineated, and a scheme for evaluating validity of the inventory is presented. PMID- 1454502 TI - Effect of adding cognitively demanding tasks on soccer skill performance. AB - The effect of adding cognitively demanding elements to the performance of a real world motor task in which functional interference among the elements in performance existed was investigated across level of expertise. The primary task involved running as quickly as possible through a 15.25-m slalom course. Two secondary tasks were used, dribbling of a soccer ball and identification of geometric shapes projected on a screen located at the end of the slalom course. 4 novice, 5 intermediate, and 5 expert female soccer players served as subjects and performed three trials each of three experimental conditions: running through the slalom course, running through the slalom course while dribbling a soccer ball, and running through the slalom course while dribbling a soccer ball and identifying geometric shapes. Analysis of variance using a 3 (experimental condition) x 3 (level of expertise) design gave significant main effects and a significant interaction. The latter indicated that, although the addition of cognitively demanding elements caused a decrement in performance, the amount of decrement decreased as level of expertise increased. It was concluded that structural interference between elements of performance decreased the positive effect of automation of one element on dual task performance. PMID- 1454503 TI - Is perception of exertion a unique characteristic? AB - This study assessed the extent to which perception of exertion (RPE), as measured by Borg's 1971 scale using bicycle ergometry, is a unique perceptual trait. Correlations run for 35 subjects between RPE and a battery of seven perceptually oriented tasks were not significant, implying that RPE may be a unique perceptual ability. PMID- 1454504 TI - An unusual variant of Capgras syndrome. AB - In a 40-yr.-old man a variant of Capgras syndrome called reverse subjective doubles is described. The unusual feature of the case was the presence of a delusion that the patient had been transformed into someone else. PMID- 1454505 TI - Use of reinforcement to increase independence in physical fitness performance of profoundly mentally retarded youth. AB - The purpose of this study was to examine the influence of verbal praise and verbal praise plus music or vibratory reinforcement on the level of independent performance on abdominal strength and endurance, lower back and hip flexibility, and upper body strength/endurance exercises of 12 profoundly mentally retarded, ambulatory youth, ages 10 to 18 years. A single-subject AB design with a control group was used to assess the difference in performance of physical fitness under the baseline condition of no reinforcement and under the two experimental conditions of verbal praise and verbal praise plus music or vibratory reinforcement. In contrast to previous results reported in the literature, verbal praise and verbal praise plus music or vibratory reinforcement were not effective in increasing the level of independence in performing selected physical fitness tasks. PMID- 1454506 TI - Influence of diazepam on prospective time estimation. AB - 24 students, after intake of diazepam or placebo, performed a psychomotor test of finger tapping as a prospective time-estimation task. The task was less overestimated by those who were under the influence of the drug than by the 12 subjects to whom the placebo was given. PMID- 1454507 TI - The dermo-optical perception of color as an information source for blind travelers. AB - Dermo-optical color perception refers to a person's ability to distinguish color surfaces through "skin perception" without the use of sight. The aims of this study were (1) to assess prior research findings which apparently demonstrated the existence of dermo-optical color perception and (2) to explore the possibilities of using color to indicate reference points for blind travellers. Three experiments were conducted with 20 congenitally blind subjects and a sighted blindfolded control group matched on age, sex, and education. In Exp. 1 on a discrimination task subjects were asked if two boards were of the same color and on a pairing task were asked to match a colored board with one among a set of three boards having the same color. In Exp. 2 the discrimination task was identical to that in Exp. 1, but instead of using boards perceived through haptic exploration, we used colored cubicles in which the whole body would be exposed to the color. In Exp. 3 subjects were asked to walk along the corridor of a labyrinthine set-up and to identify any changes of color they could perceive. The experiments were designed to provide measures of reliability of subjects' responses. Analysis showed little or no support for the ability to perceive color by dermo-optical means. The comparisons of the blind and the sighted control groups were nonsignificant. On the basis of our findings, the use of color to help blind travellers has to be rejected. The paper concludes with a discussion suggesting reasons for the contradictory results emerging from studies on dermo optical color perception. PMID- 1454508 TI - [Orthodontic treatment of adults--luxury or necessity?]. PMID- 1454509 TI - [Human factor. Possibilities and limits of motivation of duration of behavior changes]. PMID- 1454510 TI - [Adhesive dentistry in concept of periodontologists]. PMID- 1454511 TI - [Suction complete denture]. PMID- 1454512 TI - [Crowns fractures--diagnosis and therapy]. PMID- 1454513 TI - Nursing DataSource 1992. Volume II. Focus on practical/vocational nursing. PMID- 1454514 TI - Human rights remains basic tenet for nursing. PMID- 1454515 TI - Cloning by recognition site screening of two novel GT box binding proteins: a family of Sp1 related genes. AB - Previous analyses of the uteroglobin gene promoter revealed a GT1 box which is also found in the SV40 enhancer. The GT1 element in the context of the uteroglobin promoter is active in Ishikawa cells, a human endometrial cell line, but not in HeLa cells. Here we report the cloning by recognition site screening of two factors (SPR-1 and SPR-2) which bind to this GT1 motif. SPR-1 and SPR-2 are homologues of the transcription factor Sp1. All three proteins are closely related members of a gene family encoding proteins with very similar structural features. Like Sp1, SPR-1 and SPR-2 contain glutamine and serine/threonine rich amino acid stretches. Most significantly, the DNA binding domains of all three proteins are highly conserved and they recognize GT as well as GC boxes identically. SPR-2 mRNA is expressed ubiquitously, whereas SPR-1 transcripts are abundant in the brain but barely detectable in other organs. The possible function of these factors for the activity of the uteroglobin promoter is discussed. PMID- 1454516 TI - DNA damage response of cloned DNA beta-polymerase promoter is blocked in mutant cell lines deficient in protein kinase A. AB - DNA beta-polymerase (beta-pol), one of the recognized DNA polymerizing enzymes in vertebrates, has a role in 'very short patch' gap-filling synthesis during nucleotide excision DNA repair. In human and mouse, the enzyme is encoded by a single-copy gene located on the short arm of chromosome 8 near the centromere. In a series of studies, we have found that the cloned human beta-pol promoter is regulated by signals acting through the single ATF/CRE palindrome in the core promoter. These signals include transactivation by: adenovirus E1a/E1b proteins; activated p21ras; and in CHO cells, treatment with the DNA damaging agent MNNG. Hence, several types of stimulatory signals are mediated through the single ATF/CRE site, including DNA damage induction. To understand the mechanism of beta pol promoter activation by MNNG in CHO cells, we asked whether induction of the cAMP/protein kinase A pathway can increase transcription of the cloned promoter in this system. Agents that increase cellular cAMP levels (8-BrcAMP; forskolin and IBMx) activated the beta-pol promoter fusion gene in transient expression experiments, and a mutation in the ATF/CRE palindrome blocked this response. Thus, the ATF/CRE site appears to be cAMP responsive in the CHO cell system. We found that the activation of the cloned beta-pol promoter by MNNG does not occur with two mutant CHO cell lines that are deficient in protein kinase A activity. Further, simultaneous treatment of wild-type CHO cells, with MNNG and to elevate cAMP, failed to result in an additive effect for activation of the beta-pol promoter. Thus, these effectors may act through a common pathway. These results suggest that the activation of the cloned beta-pol promoter in CHO cells following MNNG treatment is mediated through the cAMP/protein kinase A signal transduction pathway. PMID- 1454517 TI - Control of Drosophila Sex-lethal pre-mRNA splicing by its own female-specific product. AB - Drosophila melanogaster somatic sexual differentiation is accomplished by serial function of the products of sex-determination genes. Sex-lethal (Sxl), is one such gene. It is functionally expressed only in female flies. The sex-specific expression of this gene is regulated by alternative mRNA splicing which results in either the inclusion or exclusion of the translation stop codon containing third exon. Although previous genetic and molecular analyses suggest that functional Sxl expression is maintained by a positive feedback loop, where the female-specific Sxl product promotes the synthesis of its own female-specific mRNA, the mechanistic details of such regulation have remained unclear. We have developed a cotransfection system using Drosophila cultured (Kc) cells in which Sxl primary transcripts are expressed with or without the female specific Sxl product. Here we show that the female-specific Sxl product induces the synthesis of its own female-specific mRNA by negative control of male-specific splicing. Deletion, substitution, and binding experiments have demonstrated that multiple uridine-rich sequences in the introns around the male-specific third exon are involved in the splicing regulation of Sxl pre-mRNA. PMID- 1454518 TI - Cloning and characterization of the Drosophila homolog of the xeroderma pigmentosum complementation-group B correcting gene, ERCC3. AB - Previously the human nucleotide excision repair gene ERCC3 was shown to be responsible for a rare combination of the autosomal recessive DNA repair disorders xeroderma pigmentosum (complementation group B) and Cockayne's syndrome (complementation group C). The human and mouse ERCC3 proteins contain several sequence motifs suggesting that it is a nucleic acid or chromatin binding helicase. To study the significance of these domains and the overall evolutionary conservation of the gene, the homolog from Drosophila melanogaster was isolated by low stringency hybridizations using two flanking probes of the human ERCC3 cDNA. The flanking probe strategy selects for long stretches of nucleotide sequence homology, and avoids isolation of small regions with fortuitous homology. In situ hybridization localized the gene onto chromosome III 67E3/4, a region devoid of known D.melanogaster mutagen sensitive mutants. Northern blot analysis showed that the gene is continuously expressed in all stages of fly development. A slight increase (2-3 times) of ERCC3Dm transcript was observed in the later stages. Two almost full length cDNAs were isolated, which have different 5' untranslated regions (UTR). The SD4 cDNA harbours only one long open reading frame (ORF) coding for ERCC3Dm. Another clone (SD2), however, has the potential to encode two proteins: a 170 amino acids polypeptide starting at the optimal first ATG has no detectable homology with any other proteins currently in the data bases, and another ORF beginning at the suboptimal second startcodon which is identical to that of SD4. Comparison of the encoded ERCC3Dm protein with the homologous proteins of mouse and man shows a strong amino acid conservation (71% identity), especially in the postulated DNA binding region and seven 'helicase' domains. The ERCC3Dm sequence is fully consistent with the presumed functions and the high conservation of these regions strengthens their functional significance. Microinjection and DNA transfection of ERCC3Dm into human xeroderma pigmentosum (c.g. B) fibroblasts and group 3 rodent mutants did not yield detectable correction. One of the possibilities to explain these negative findings is that the D.melanogaster protein may be unable to function in a mammalian repair context. PMID- 1454519 TI - DNA conformational change induced by the bacteriophage phi 29 connector. AB - Translocation of viral DNA inwards and outwards of the capsid of double-stranded DNA bacteriophages occurs through the connector, a key viral structure that is known to interact with DNA. It is shown here that phage phi 29 connector binds both linear and circular double-stranded DNA. However, DNA-mediated protection of phi 29 connectors against Staphylococcus aureus endoprotease V8 digestion suggests that binding to linear DNA is more stable than to circular DNA. Endoprotease V8-protection assays also suggest that the length of the linear DNA required to produce a stable phi 29 connector-DNA interaction is, at least, twice longer than the phi 29 connector channel. This result is confirmed by experiments of phi 29 connector-protection of DNA against DNase I digestion. Furthermore, DNA circularization assays indicate that phi 29 connectors restrain negative supercoiling when bound to linear DNA. This DNA conformational change is not observed upon binding to circular DNA and it could reflect the existence of some left-handed DNA coiling or DNA untwisting inside of the phi 29 connector channel. PMID- 1454520 TI - Bacteriophage and spliceosomal proteins function as position-dependent cis/trans repressors of mRNA translation in vitro. AB - The translational regulation of ferritin expression currently represents the only well characterized example for eukaryotic translational control by high affinity interactions between a specific cytoplasmic protein, iron regulatory factor [IRF], and an mRNA-binding site, the iron-responsive element [IRE], located in the 5' untranslated region [UTR] of ferritin mRNAs. To elucidate whether IRE/IRF may represent the first physiological example of a more general mechanism for mRNA-specific translational control, high affinity RNA-binding sites for the bacteriophage MS2 coat protein or the spliceosomal protein U1A were introduced into the 5' UTR of capped chloramphenicol acetyltransferase [CAT] transcripts. In the absence of these RNA-binding proteins, CAT mRNA was efficiently translated. Addition of purified MS2 coat protein or U1A caused a specific, dose-dependent repression of CAT biosynthesis in rabbit reticulocyte and wheat germ in vitro translation systems. The translational blockage imposed by the RNA/protein complex was reversible and did not alter the stability of the repressed mRNAs. Translational repression caused by binding of U1A or MS2 proteins to their target mRNAs is shown to be position-dependent in vitro. Thus, mRNA/protein complexes without an a priori role in eukaryotic mRNA translation function as translational effectors with characteristics resembling those of IRE/IRF. PMID- 1454521 TI - Mutation of the casein kinase II phosphorylation site abolishes the anti proliferative activity of p53. AB - The p53 tumour suppressor protein is phosphorylated by several protein kinases, including casein kinase II. In order to understand the functional significance of phosphorylation by casein kinase II, we have introduced mutations at serine 386 in mouse p53, the residue phosphorylated by this kinase, and investigated their effects on the ability of p53 to arrest cell growth. Replacement of serine 386 by alanine led to loss of growth suppressor activity, while aspartic acid at this position partially retained suppressor function. These data suggest that the anti proliferative activity of p53 is activated by phosphorylation at serine 386, and establish a direct link between the covalent modification of a growth suppressor protein and regulation of its activity in mammalian cells. PMID- 1454523 TI - Differential splicing creates a diversity of transcripts from a neurospecific developmentally regulated gene encoding a protein with new zinc-finger motifs. AB - We have cloned a novel neurospecific gene, named neuro-d4, by differential screening a rat cerebral cortex cDNA library. Northern blot hybridization showed that neuro-d4 expression is restricted to neuronal tissues both in newborn and adult animals. The level of neuro-d4 mRNA in the rat central nervous system is high during the later stages of embryonic development and gradually decreases during the postnatal period. In situ hybridization suggests that the gene transcripts are localized in neuronal cell bodies. Nucleotide sequences of overlapped cDNA clones and all 12 exons in genomic clone were determined. The deduced protein has consensus sequences for a nuclear localization signal, a Kruppel-type zinc-finger and a new type of cysteine/histidine-rich motif resembling zinc-fingers. Several differential splicing variants were found, each of which influences the structure of the encoded protein. PMID- 1454522 TI - Fission yeast cdc21+ belongs to a family of proteins involved in an early step of chromosome replication. AB - The cdc21+ gene of Schizosaccharomyces pombe was originally identified in a screen for cdc mutants affecting S phase and nuclear division. Here we show that the cdc21+ gene product belongs to a family of proteins implicated in DNA replication. These include the Saccharomyces cerevisiae MCM2 and MCM3 proteins, which are needed for the efficient function of certain replication origins, and S.cerevisiae CDC46, which is required for the initiation of chromosome replication. The cdc21 mutant is defective in the mitotic maintenance of some plasmids, like mcm2 and mcm3. The mutant arrests with a single nucleus containing two genome equivalents of DNA, and maintains a cytoplasmic microtubular configuration. Activation of most, but not all, replication origins in the mutant may result in failure to replicate a small proportion of the genome, and this could explain the arrest phenotypes. Using the polymerase chain reaction technique, we have identified new cdc21(+)-related genes in S.cerevisiae, S.pombe and Xenopus laevis. Our results suggest that individual members of the cdc21(+) related family are highly conserved in evolution. PMID- 1454524 TI - Binding of Xenopus oocyte masking proteins to mRNA sequences. AB - It has been shown previously that maternal mRNA, synthesized and stored in growing oocytes, is stabilized and blocked from translation through various mechanisms including restricted polyadenylation and the binding of proteins to 3' regulatory elements. In addition to binding sequence-specific proteins, the bulk of stored mRNA is packaged with a set of 'masking' proteins, the most abundant of which are the phosphoproteins pp56 and pp60. In this report these proteins are shown to be bound to heterogeneous mRNA sequences and not to the 3' poly(A) tract. Crosslinking studies demonstrate that all of the pp56/60 present makes direct contact with the RNA. In vitro binding studies confirm that pp56/60 interact with single-stranded RNA of heterogeneous sequence, such as occurring in the maternal mRNA encoding cyclin B1. However, binding is equally effective to capped and polyadenylated cyclin mRNA, to truncated mRNA lacking 5' and 3' non coding regions and even to the antisense sequence. Lengths of 70-80 nucleotides are protected from ribonuclease digestion after protein binding. Although no extended binding motif could be detected, binding does appear to have some specificity in that it is not competed out by 100-fold excess of double-stranded RNA, transfer RNA, poly(A) and various other homopolymers and heteropolymers. The sequence which competes most efficiently is the mixed polypyrimidine, poly(C,U). Crosslinking of RNA-protein complexes, followed by ribonuclease digestion, suggests that the arrangement of proteins on RNA is as dimers. Dimerization appears to be stabilized by phosphorylation of pp56/60. These results are discussed in terms of the known structures of pp56/60. PMID- 1454525 TI - The 2-amino group of guanine is absolutely required for specific binding of the anti-cancer antibiotic echinomycin to DNA. AB - The 2-amino group of guanine is believed to be a critical determinant of potential DNA binding sites for echinomycin and related quinoxaline antibiotics. In order to probe its importance directly we have studied the interaction between echinomycin and DNA species in which guanine N(2) is deleted by virtue of substitution of inosine for guanosine residues. The polymerase chain reaction was used to prepare inosine-substituted DNA. Binding of echinomycin, assessed by DNAse I footprinting, was practically abolished by incorporation of inosine into one or both strands of DNA. We conclude that both the purines in the preferred CpG binding site need to bear a 2-amino group to interact with echinomycin. PMID- 1454526 TI - The mitochondrial gene encoding ribosomal protein S12 has been translocated to the nuclear genome in Oenothera. AB - The Oenothera mitochondrial genome contains only a gene fragment for ribosomal protein S12 (rps12), while other plants encode a functional gene in the mitochondrion. The complete Oenothera rps12 gene is located in the nucleus. The transit sequence necessary to target this protein to the mitochondrion is encoded by a 5'-extension of the open reading frame. Comparison of the amino acid sequence encoded by the nuclear gene with the polypeptides encoded by edited mitochondrial cDNA and genomic sequences of other plants suggests that gene transfer between mitochondrion and nucleus started from edited mitochondrial RNA molecules. Mechanisms and requirements of gene transfer and activation are discussed. PMID- 1454527 TI - Alteration by site-directed mutagenesis of the conserved lysine residue in the consensus ATP-binding sequence of the RecB protein of Escherichia coli. AB - The RecB and RecD subunits of the RecBCD enzyme of Escherichia coli contain amino acid sequences similar to a consensus mononucleotide binding motif found in a large number of other enzymes. We have constructed by site-directed mutagenesis a lysine-to-glutamine mutation in this sequence in the RecB protein. The mutant enzyme (RecB-K29Q-CD) has essentially no nuclease or ATP hydrolysis activity on double-stranded DNA, showing the importance of RecB for unwinding double-stranded DNA. However, ATP hydrolysis stimulated by single-stranded DNA is reduced by only about 5-8-fold compared to the wild-type, nuclease activity on single-stranded DNA is reduced by less than 2-fold, and the nuclease activity of the RecB-K29Q-CD enzyme requires ATP. The effects of the RecB mutation suggest that the RecD protein hydrolyzes ATP and can stimulate the RecBCD enzyme nuclease activity on single-stranded DNA. PMID- 1454528 TI - The developmental regulation of the human zeta-globin gene in transgenic mice employing beta-galactosidase as a reporter gene. AB - We have investigated the developmental and tissue specific expression of the human embryonic zeta-globin gene in transgenic mice. A construct containing 550 bp of zeta-globin 5' flanking region, fused to a beta-galactosidase (lacZ) reporter gene and linked to the locus control region (LCR)-like alpha positive regulatory element (alpha PRE) was employed for the production of transgenic mice. Firstly, we compared the number of live born transgenic mice containing this construct to the number of live born transgenic mice containing the entire zeta-globin gene linked to the alpha PRE or the beta LCR. Data showed that 12% of mice generated from eggs injected with zeta-promoter/lacZ/alpha PRE DNA were transgenic compared to only 2% of mice generated from eggs injected with the entire zeta-globin gene linked to the alpha PRE or the beta LCR. The reduced number of live born transgenic mice containing the latter constructs suggests that death of transgenic embryos, possibly due to thalassaemia, may be occurring. X-gal staining of whole embryos containing the lacZ gene revealed that zeta globin promoter activity was most pronounced at 8.5-9.5 days of development and was restricted to erythroid cells. By 15 days of development, no zeta-globin promoter activity was detected. These results suggest that the alpha PRE can direct high level expression from the zeta-globin promoter and that sequences required for the correct tissue and developmental specific expression of the human zeta-globin gene are present within 550 bp's of 5' flanking region. Sequences within the body of the zeta-globin gene or 3' of the cap site do not appear to be necessary for correct zeta-globin developmental regulation. PMID- 1454530 TI - Differentially regulated malate synthase genes participate in carbon and nitrogen metabolism of S. cerevisiae. AB - We have isolated a second gene (MLS1), which in addition to DAL7, encodes malate synthase from S. cerevisiae. Expression of the two genes is specific for their physiological roles in carbon and nitrogen metabolism. Expression of MLS1, which participates in the utilization of non-fermentable carbon sources, is sensitive to carbon catabolite repression, but nearly insensitive to nitrogen catabolite repression. DAL7, which participates in catabolism of the nitrogenous compound allantoin, is insensitive to carbon catabolite repression, but highly sensitive to nitrogen catabolite repression. Results obtained with null mutations in these genes suggest that S. cerevisiae contains at least one and perhaps two additional malate synthase genes. PMID- 1454529 TI - In vitro and in vivo protein--DNA interactions on the rat erythroid-specific L' pyruvate kinase gene promoter. AB - The rat L-type pyruvate kinase gene possesses two alternative tissue-specific promoters, located 472 bp apart; the upstream L' promoter is erythroid-specific and the downstream L promoter is hepatocyte-specific. The erythroid-specific L' promoter is strongly active in fetal liver at day 17 of gestation, while its activity rapidly decreases thereafter. A L' promoter fragment spanning from nucleotide -320 to +10 with respect to the cap site is able to direct a weak but erythroid-specific transcription in a cell-free system. We have used DNAse I footprinting and gel mobility shift assays to characterize and identify the binding of nuclear factors from both 17-day-old fetal liver and adult liver nuclear extracts to a 320 bp fragment of the 5' flanking region of the gene in vitro. Two clusters of erythroid-specific interactions were found. The proximal cluster consists of two GATA-1 binding sites at -50 bp and -65 bp from the transcription initiation site, immediately downstream of a CACC motif and two G/C rich elements. The distal cluster of cis-elements, located 130 bp upstream, corresponds to two GATA-1 sequences. These two sequences overlap NF1 motifs interacting with ubiquitous NF1 transcriptional factors in presence of adult hepatic extracts. Furthermore, we have examined in vivo protein-DNA interactions by DMS footprinting in livers of 17-day-old rat fetuses and adult rats. We found that the sites characterized in vitro are occupied in vivo. Therefore, in adult liver the L' promoter, although inactive, nevertheless interacts with ubiquitous factors. PMID- 1454531 TI - Oligonucleotide probes detect splicing variants in situ in Drosophila embryos. AB - We describe a method for the in situ detection of specific splicing variants. The method is based on the use of antisense oligonucleotides designed to span splice junctions labelled with digoxigenin by terminal transferase tailing. We find that the spatial patterns of Ubx splicing variants Ia and IIa are similar in early embryos, but differ in late embryos. Variant IVa is only detected in the CNS (ps6) at stages 16 and 17. We also present evidence indicating that the first splicing event is cotranscriptional. PMID- 1454532 TI - Intracellular availability of unmodified, phosphorothioated and liposomally encapsulated oligodeoxynucleotides for antisense activity. AB - We have studied factors which may effect the intracellular availability of oligonucleotides to achieve antisense activity. 15-20 mer unmodified, phosphorothioate modified and liposomally encapsulated oligodeoxynucleotides have been tested in leukemia MOLT-3 cells. Phosphorothioate analogs penetrated and accumulated intact in cells in contrast to unmodified oligomers, which showed a high instability in cell culture medium. A slow decrease of intracellular concentration of undegraded phosphorothioate oligodeoxynucleotides was observed after cell treatment and could be predominantly explained by a significant efflux transport. Using laser-assisted confocal microscopy we have observed that fluorescein 5-end-labeled phosphorothioate derivatives predominantly distributed in intracytoplasmic endocytic vesicles following cell treatment. The end-capped version of phosphorothioate oligodeoxynucleotides exhibited greater cellular uptake than fully modified analogues while exhibiting similar biological stability. Liposome encapsulation made possible oligomer protection in serum containing medium and substantially improved cellular accumulation. Furthermore, the efflux rate of oligomer initially introduced within liposomes is 2-fold lower than that observed in cells which have been incubated with free oligonucleotides. Liposomal preparations of oligodeoxynucleotides facilitate release from endocytic vesicles, and thus, cytoplasmic and nuclear localization are observed following cell treatment. Furthermore, intracellular distribution studies demonstrate that intracellular transport of unmodified oligomers is effectively achieved using the liposomal carrier. PMID- 1454533 TI - A single nuclear gene specifies the abundance and extent of RNA editing of a plant mitochondrial transcript. AB - A number of cytosines are altered to be recognized as uridines in transcripts of the NADH-dehydrogenase subunit 3 (nad3) gene in the mitochondria of the higher plant Petunia hybrida. Here we show that the extent of editing for three of the edit sites, all of which change the encoded amino acid, varies between different Petunia lines. Genetic analysis indicates that a single nuclear gene is responsible for this variation. Interestingly, according to RNA blot hybridization analysis, RNA editing extent and transcript abundance are correlated. This observation is consistent with the hypothesis that RNA editing is a post-transcriptional event. PMID- 1454534 TI - Specific transcription from the adenovirus E2E promoter by RNA polymerase III requires a subpopulation of TFIID. AB - The early E2 (E2E) promoter of adenovirus type 2 possesses a TATA-like element and binding sites for the factors E2F and ATF. This promoter is transcribed by RNA polymerase II in high salt nuclear extracts, but by RNA polymerase III in standard nuclear extracts, as judged by sensitivity to low and high, respectively, concentrations of alpha-amanitin. Transcription by the two RNA polymerases initiated at the same site and depended, in both cases, on the TATA like sequence and upstream elements. However, RNA polymerase III transcripts, unlike those synthesized by RNA polymerase II, terminated at two runs of Ts downstream of the initiation site. Although they are not essential, sequences downstream of the initiation site increased the efficiency of E2E transcription by RNA polymerase III. Such RNA polymerase III dependent transcription required a subpopulation of the general transcription factor, TFIID: TFIID that binds weakly to phosphocellulose (0.3 M eluate) complemented a TFIID-depleted extract to restore RNAp III transcription, whereas TFIID tightly associated with phosphocellulose (1 M eluate) was unable to do so. PMID- 1454536 TI - Cloning and characterization of genes for the PvuI restriction and modification system. AB - The genes encoding the endonuclease and the methylase of the PvuI restriction and modification system were cloned in E.coli and characterized. The genes were adjacent in tandem orientation spanning a distance of 2200 bases. The PvuI endonuclease was a single polypeptide with a calculated molecular weight of 27,950 daltons. The endonuclease was easily detectable when the gene was expressed from its endogenous promotor and present on a low copy plasmid, but expression was considerably enhanced when the endonuclease gene was placed under the control of a strong promoter on a high copy plasmid. The methylase did not completely protect plasmid DNA from R.PvuI digestion until the methylase gene was placed under lac promotor control in a multicopy plasmid. In the absence of the M.PvuI methylase, expression of the R.PvuI endonuclease from the lac promotor on a multicopy plasmid was not lethal to wild type E.coli, but was lethal in a temperature-sensitive ligase mutant at the non-permissive temperature. Moreover, induction of the R.PvuI endonuclease under lambda pL promotor control resulted in complete digestion of the E.coli chromosome by R.PvuI. PMID- 1454535 TI - Intramolecular triplex potential sequence within a gene down regulates its expression in vivo. AB - Polypurine/polypyrimidine sequences have been shown to adopt intramolecular triple helix structures under torsional stress and/or at low pH. Such sequences have been observed within the the regulatory as well as the coding regions of several genes and the involvement of triple helical structure adopted by these sequences in transcriptional control has been speculated. Taking advantage of codon degeneracy we have engineered a 38 bp long intramolecular triple helix potential polypurine/polypyrimidine sequence motif between the 37th and 50th codons of beta-galactosidase gene in the plasmid pBluescriptIISK+ to investigate whether in vivo E.coli RNA polymerase would transcribe sequence motifs adopting triple helix structure, when present within the coding region of the gene. E.coli JM109 cells transformed with this construct pSBT1, exhibited 80% inhibition of beta-galactosidase expression compared to another construct pSBmT12 made using less preferred codons for identical amino acid sequence, but lacking the polypurine/polypyrimidine sequence motif. Truncated beta-galactosidase transcripts were observed for pSBT1 but not for pSBmT12. Here we report that a putative triple helix potential sequence within a gene can down regulate its expression by partially blocking the transcription elongation in vivo. PMID- 1454537 TI - 5' untranslated sequences modulate rapid mRNA degradation mediated by 3' AU-rich element in v-/c-fos recombinants. AB - One major determinant of rapid mRNA decay is the presence of AU-rich sequences located in 3' untranslated regions (UTR). To assess for the contribution of upstream sequences on the activity of the 3' AU-rich destabilizing element, we have determined the decay-rates of v-/c-fos hybrid transcripts by quantitative RNA protection analysis. In a transient expression assay, v-/c-fos recombinants generated two mRNA populations via alternative splicing and removal of an optional intron entirely located in the 5' UTR. Both mRNA species were found to be relatively stable in constructs lacking the c-fos AU-rich destabilizing element. Unexpectedly, in recombinants where intrinsic AU sequences were kept intact, only the full-length mRNA population showed high instability whereas the spliced mRNA species remained relatively stable. A v-/c-fos 5' UTR fragment encoding the optional intron was inserted into alpha-globin genes harboring either the c-fos or GM-CSF destabilizing element. The splicing and degradation patterns of these heterologous transcripts paralleled that of v-/c-fos recombinants. These observations unmasked a 5' cis-acting element in v-/c-fos mRNA whose presence is required for the activity of the AU-rich destabilizing element. They demonstrate the important role of interactions between distinct sequences on the regulation of mRNA stability. PMID- 1454538 TI - Structure and function of the murine beta-globin locus control region 5' HS-3. AB - We previously identified the murine homologue of the human beta-globin Locus Control Region (LCR) 5' HS-2. The lambda clone containing murine 5' HS-2 extends approximately 12 kb upstream from this site; here, we report the sequence of this entire upstream region. The murine homologue of 5' HS-3 is located approximately 16.0 kb upstream from the mouse epsilon y-globin gene, but no region homologous to human 5' HS-4 was present in our clone. Using a reporter system consisting of a human gamma-globin promoter driving the neomycin phosphotransferase gene (gamma neo), we tested murine LCR fragments extending from -21 to -9 kb (with respect to the epsilon y-globin gene cap site) for activity in classical enhancer and integration site assays in K562 and MEL cells. 5' HS-2 behaved as a powerful enhancer and increased the number of productive integration events (as measured by a colony assay) in both K562 and MEL cells. 5' HS-3 had no activity in K562 cells or in transiently transfected MEL cells, but was nearly as active as 5' HS 2 in the MEL cell colony assay. Two additional tests confirmed the identification of murine 5' HS-3: first, a DNA fragment containing 5' HS-3 confers copy number dependent, integration-site independent inducibility on a linked beta-globin gene in the MEL cell environment. Secondly, a strong DNAseI hypersensitive site maps to the location of the 5' HS-3 functional core in chromatin derived from MEL cells. Collectively, these data suggest that we have identified the murine homologue of human 5' HS-3, and that this site is functional when integrated into the chromatin of MEL cells but not K562 cells. 5' HS-3 may therefore contain information that contributes to the development-specific expression of the beta like globin genes. PMID- 1454539 TI - Identifying constraints on the higher-order structure of RNA: continued development and application of comparative sequence analysis methods. AB - Comparative sequence analysis addresses the problem of RNA folding and RNA structural diversity, and is responsible for determining the folding of many RNA molecules, including 5S, 16S, and 23S rRNAs, tRNA, RNAse P RNA, and Group I and II introns. Initially this method was utilized to fold these sequences into their secondary structures. More recently, this method has revealed numerous tertiary correlations, elucidating novel RNA structural motifs, several of which have been experimentally tested and verified, substantiating the general application of this approach. As successful as the comparative methods have been in elucidating higher-order structure, it is clear that additional structure constraints remain to be found. Deciphering such constraints requires more sensitive and rigorous protocols, in addition to RNA sequence datasets that contain additional phylogenetic diversity and an overall increase in the number of sequences. Various RNA databases, including the tRNA and rRNA sequence datasets, continue to grow in number as well as diversity. Described herein is the development of more rigorous comparative analysis protocols. Our initial development and applications on different RNA datasets have been very encouraging. Such analyses on tRNA, 16S and 23S rRNA are substantiating previously proposed associations and are now beginning to reveal additional constraints on these molecules. A subset of these involve several positions that correlate simultaneously with one another, implying units larger than a basepair can be under a phylogenetic constraint. PMID- 1454540 TI - The mouse beta-globin locus control region: hypersensitive sites 3 and 4. AB - The human beta-globin LCR plays a key role in the transcriptional regulation of the beta-globin locus and comprises four erythroid specific DNase I hypersensitive sites, designated 5'HS1-4. We have now isolated genomic clones containing 5'HS3 and 5'HS4 of the mouse beta-globin LCR. 5'HS3 and 5'HS4 are located 15 kb and 22 kb upstream of the mouse epsilon y-globin gene, respectively. Sequence analysis of murine 5'HS3 and 5'HS4 reveals a significant degree of sequence conservation with their human homologues, including the presence of recognition sites for functionally relevant transcription factors. 5'HS3 and 5'HS4 regions were found to form hypersensitive sites in nuclei from murine erythroid cells, but not in nuclei from a variety of nonerythroid haematopoietic cell lines. Analysis of different mouse strains revealed the existence of a polymorphism that alters the spacing between 5'HS3 and 5'HS4. Taken together, our results emphasize the extent of evolutionary conservation and complexity of mammalian beta-globin LCRs. Finally, the cloning of mouse 5'HS3 and 5'HS4 will facilitate the molecular analysis of LCR function in the mouse model. PMID- 1454541 TI - An ultraviolet light-damaged DNA recognition protein absent in xeroderma pigmentosum group E cells binds selectively to pyrimidine (6-4) pyrimidone photoproducts. AB - The binding specificity was defined of a human ultraviolet light-damaged DNA recognition protein (UV-DRP), the activity of which is absent in some xeroderma pigmentosum complementation group E cells. Our results suggest that cyclobutane pyrimidine dimers (CPDs) are not high affinity UV-DRP binding sites--a finding consistent with other reports on this protein (Hirschfeld et al., (1990) Mol. Cell Biol., 10, 2041-2048). A major role for 6-4 photoproducts in UV-DRP binding was suggested in studies showing that irradiated oligonucleotides containing a T4C UV box sequence, which efficiently forms a TC 6-4 photoproduct, was a superior substrate for the UV-DRP when compared to a similar irradiated oligonucleotide having a T5 sequence. The latter sequence forms CPDs at a much higher frequency than 6-4 photoproducts. In a more direct approach, T4C containing oligonucleotides complexed with the UV-DRP were separated from the unbound oligonucleotide fraction and the frequencies of 6-4 photoproducts in the two DNA populations were compared. The UV-DRP-bound fraction was highly enriched for the 6-4 lesion over the unbound fraction supporting the conclusion that 6-4 photoproducts are the principal binding cues for the UV-DRP. PMID- 1454543 TI - Identification of two large subdomains in TFIIE-alpha on the basis of homology between Xenopus and human sequences. PMID- 1454542 TI - RecA-AC: single-site cleavage of plasmids and chromosomes at any predetermined restriction site. AB - We have developed a novel version of the Achilles' Cleavage (AC) reaction in which virtually any restriction site on DNA of any size can be converted to a unique cleavage site. We first polymerized RecA protein on a synthetic oligodeoxyribonucleotide (oligo) in the presence of a nonhydrolyzable ATP analogue to generate oligo:RecA nucleoprotein filaments. These filament were then incubated with plasmid or intact chromosomal DNA from Saccharomyces cerevisiae to form stable complexes in the yeast LEU2 gene at the target sequence identical (or complementary) to that of the oligo. When HhaII (HinfI) methyltransferase (M.HhaII) was added, all of the recognition sites for HhaII with the exception of the one protected by the RecA filament were methylated and thus no longer cleaved by the cognate restriction endonuclease (HinfI). After inactivation of the RecA and the M.HhaII, HinfI was used to efficiently cleave the plasmid or chromosome specifically at the targeted restriction site. Since oligos specific for any sequence can be easily synthesized and the other reagents necessary to perform RecA-mediated AC (RecA-AC) reactions on both plasmids and intact chromosomes are readily available, this procedure can be applied immediately to the precise dissection and analysis of genomic DNA from any source and to any other research problem requiring efficient, highly specific cleavage of DNA at predetermined sites. PMID- 1454544 TI - Molecular cloning and nucleotide sequence of the DNA polymerase gene from Thermus flavus. PMID- 1454545 TI - Nucleotide sequence of a fission yeast gene encoding the DEAH-box RNA helicase. PMID- 1454546 TI - The phosphoprotein (P) gene of the rhabdovirus Piry: its cloning, sequencing, and expression in Escherichia coli. PMID- 1454547 TI - Nucleotide sequence of a maize chloroplast DNA fragment containing an inversion breakpoint, trnG (GCC), trnG (UCC), trnfM, and a trnG pseudogene. PMID- 1454548 TI - Sequence of cDNA for Xenopus XZFY-1. PMID- 1454549 TI - Human ribosomal RNA intergenic spacer sequence. PMID- 1454550 TI - Nucleotide sequence of the phoP gene encoding PhoP, the response regulator of the phosphate regulon of Bacillus subtilis. PMID- 1454551 TI - Nucleotide sequence of a rabbit cDNA encoding elongation factor 1 gamma. PMID- 1454552 TI - A restriction enzyme, BpuI is an isoschizomer of BanII. PMID- 1454553 TI - A rapid and inexpensive method for isolation of shuttle vector DNA from yeast for the transformation of E.coli. PMID- 1454554 TI - The use of purine-rich oligonucleotides in triplex-mediated DNA isolation and generation of unidirectional deletions. PMID- 1454555 TI - In vitro transcription complementation assay with miniextracts of transiently transfected COS-1 cells. PMID- 1454556 TI - The stability of different forms of double-stranded decoy DNA in serum and nuclear extracts. PMID- 1454557 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1454559 TI - Life savers. PMID- 1454558 TI - Nursing Times open learning programme. R4: the real world of research. Part (ii): Research ethics. (continuing education credit). PMID- 1454560 TI - Changing problems. PMID- 1454561 TI - High anxiety. PMID- 1454562 TI - Menu changes. PMID- 1454564 TI - Capital punishment. PMID- 1454563 TI - Safer children. PMID- 1454565 TI - Hospital at home. Self-service. PMID- 1454566 TI - Hospital at home. Hip home. PMID- 1454567 TI - Hospital at home. Advanced states. PMID- 1454568 TI - Sterile condition. PMID- 1454569 TI - Lifting developments. PMID- 1454570 TI - Positive support. PMID- 1454571 TI - The write way. PMID- 1454572 TI - The key to innovation. PMID- 1454574 TI - Continence. Equal rites for men. PMID- 1454573 TI - Continence. The reuser's guide. PMID- 1454577 TI - Nursing Times open learning programme. P10. Delivery of care. Part (ii): Delivery systems (continuing nursing education). PMID- 1454576 TI - Continence. Continent's provision. PMID- 1454575 TI - Continence. Undercover trials unfair. PMID- 1454578 TI - Men's hidden illness. PMID- 1454579 TI - Management fads? Job evaluation; performance-related pay. PMID- 1454580 TI - The Tomlinson report. London's fate. PMID- 1454581 TI - The Tomlinson report. The nurse's voice. Interview by Bernadette Friend. PMID- 1454582 TI - Letter from Barts. PMID- 1454583 TI - Breaking the sound barrier. Interview by Ruth Devlin. PMID- 1454584 TI - Eating disorders. Beating bulimia. PMID- 1454585 TI - Eating disorders. Thin excuses. PMID- 1454586 TI - Nurse practitioners. A wider frame of reference. PMID- 1454587 TI - Working together. PMID- 1454588 TI - The intensive care experience. PMID- 1454589 TI - Systems of life. The nervous system. 2. PMID- 1454590 TI - Oh baby. PMID- 1454591 TI - Wound care. Community clinics. PMID- 1454593 TI - Wound care. An A&E approach. PMID- 1454592 TI - Wound care. Home help. PMID- 1454594 TI - Nursing Times open learning programme. P11. Models for care. Part (i): Medical, social and nursing models (continuing education credit). PMID- 1454595 TI - Public inconvenience. PMID- 1454596 TI - Upsetting the mix. PMID- 1454597 TI - Emergency pressures. PMID- 1454598 TI - New friends. PMID- 1454599 TI - The poverty trap. PMID- 1454600 TI - Aid for the vulnerable. Interview by Bernadette Friend. PMID- 1454601 TI - The big chill. PMID- 1454602 TI - Sexual harassment. Improper conduct. PMID- 1454603 TI - Sexual harassment. Tip of the iceberg? PMID- 1454604 TI - Debating on death. PMID- 1454605 TI - Hot pursuit. PMID- 1454606 TI - Keeping body and soul together. PMID- 1454607 TI - Midwifery. Just another miscarriage? PMID- 1454608 TI - Pain-free states. PMID- 1454609 TI - A good career move. Interview by Daloni Carlisle. PMID- 1454610 TI - Pre-operative fasting. AB - This descriptive research study replicates that of Hamilton-Smith and investigates the current practice of pre-operative fasting. It was found that, 20 years on, the management of pre-operative fasting was still largely unchanged. Despite the recognition of vast potential complications of prolonged fasting, most patients were deprived of food and fluid for considerable lengths of time before general anaesthesia--far beyond the acceptable maximum fasting time of 12 hours. However, a small number of experienced nurses challenged the tradition and successfully reduced pre-operative fasting near to the accepted minimum and thereby provided adequate nutrition for patients. PMID- 1454611 TI - Primary nursing. A new look. PMID- 1454612 TI - Primary nursing. Tried and tested. PMID- 1454613 TI - Danger on tap. PMID- 1454614 TI - Invisible women. PMID- 1454615 TI - An endangered body? PMID- 1454616 TI - Meeting unmet needs. PMID- 1454617 TI - The Tomlinson report: community strategy. PMID- 1454618 TI - Prescribed delay. PMID- 1454619 TI - Breaking the rules. PMID- 1454620 TI - Preparing for loss. PMID- 1454621 TI - Keeping in touch. PMID- 1454622 TI - Second-class citizens? PMID- 1454623 TI - Diabetes. Switching to insulin. PMID- 1454624 TI - Making sense out of hypothermia. PMID- 1454625 TI - When words fail. PMID- 1454626 TI - A lesson in grief. PMID- 1454627 TI - Memories of Molly. PMID- 1454628 TI - Building bridges. PMID- 1454629 TI - Mental health. Relax for health. PMID- 1454630 TI - Home away from home. PMID- 1454631 TI - Security screening. PMID- 1454632 TI - Mental health. Involuntary cohabitees. PMID- 1454633 TI - Mental health. Talk--don't inject. PMID- 1454634 TI - Mental health. Just lip-service? PMID- 1454635 TI - Emergency care of children in shelters. AB - Children living in homeless shelters often lack the health care resources usually available to other children. They are often more acutely and chronically ill than domiciled children and frequently use the emergency department (ED) as their point of entry into the health care system. To identify differences in health status, we surveyed sheltered children and domiciled controls during a nine-month period in our ED. One hundred sixty-two families completed a self-administered questionnaire during the study period: 54 homeless and 108 age-matched controls. Mean patient age was 3.4 years, mean maternal age was 27 years in both groups, and average time spent in shelters was 7.8 months. Shelter families had more children, more single mothers, and higher rates of unemployment and uninsurance than did control families. Shelter children showed greater frequencies of immunization delay, lack of TB testing, and lack of a regular health care site and higher rates of medical admissions from the ED. These data show that children in shelters have limited personal, financial, and medical resources and suggest that there are significant disparities in health status. These patients need to be identified when they present to the ED in order to meet subtle, as well as obvious, health needs. PMID- 1454636 TI - Aeromedical transport services accepting pediatric patients and their abidance by published guidelines. AB - The number of aeromedical transport services accepting pediatric patients (ATSP) in the United States has increased greatly over the past decade. Most aeromedical transport services are primarily designed for adults but will also transport children. Suggested guidelines for ATSP were published by the American Academy of Pediatrics (AAP) in 1986. This survey of 65 ATSP and their abidance by the major AAP guidelines showed that two thirds of the ATSP were based at facilities with pediatric tertiary care capabilities; most ATSP were not directed by pediatric critical care (PCC) or pediatric emergency care (PEC) specialists; most transport team personnel were not trained in PCC or PEC; most ATSP had specific protocols for different clinical situations; most ATSP had separate equipment appropriate for pediatric patients; and there was little variation in transport team composition based on different clinical situations. In summary, all ATS surveyed transported children, but few were aware of the AAP guidelines, and only one in 65 was in complete abidance with the recommendations. PMID- 1454637 TI - Iron absorption from chewable vitamins with iron versus iron tablets: implications for toxicity. AB - The medical literature contains few, if any, reports of severe iron (Fe) poisonings from ingestion of chewable multivitamins with iron. One possible explanation for this observation is that iron from multivitamins is more poorly absorbed than iron from iron tablets. To compare iron absorption from multivitamins with iron absorption from ferrous fumarate tablets, male adult volunteers were given 6 mg of elemental Fe/kg body weight as chewable multivitamins with iron or as crushed ferrous fumarate tablets in a crossover study. Serum Fe and total iron binding capacity (TIBC) were determined prior to administration of the tablets and one, two, four, and six hours after ingestion. Statistical analyses demonstrated increased and more rapid absorption of Fe from the multivitamin preparation. These results suggest that iron is well absorbed from chewable multivitamins with iron and should theoretically have the potential for producing serious toxicity when taken in overdose. The reasons that such toxicity is not commonly seen clinically are discussed, and a plan for further investigation of this issue is proposed. PMID- 1454638 TI - The role of abdominal x-rays in the diagnosis and management of intussusception. AB - The management of intussusception requires early diagnosis and reduction with either barium enema or surgical intervention. Supine and erect abdominal radiographs are often obtained prior to ordering a barium enema. In many pediatric centers, the critical, initial interpretation of these radiographs is made by nonradiologists and, in most instances, by pediatric emergency physicians. We determined the sensitivity and specificity of abdominal radiographs in diagnosing intussusception when interpreted by these physicians. Six full-time pediatric emergency physicians evaluated 126 radiographs from 42 patients with intussusception, 42 in whom the disease was clinically suspected but ruled out, and 42 in whom the final radiology report was "normal." These were presented to pediatric emergency physicians in a blinded, randomized sequence without any additional clinical information. These physicians then identified patients for whom they would proceed to barium enema. The mean sensitivity was 80.5% (range, 71-93%), and the mean specificity was 58% (range, 48-69%). This compares favorably to the sensitivity of signs and symptoms, and we conclude that plain and upright abdominal films are a useful adjunct for the clinician evaluating patients for suspected intussusception. PMID- 1454639 TI - Are skull radiographs useful in the evaluation of asymptomatic infants following minor head injury? AB - Head injuries constitute a common problem in the pediatric population. Recent studies indicate that infants are at increased risk for skull fractures following head trauma. The purpose of our study is to examine the utility of skull radiographs in asymptomatic infants presenting after a minor head injury. We retrospectively reviewed the records of all head-injured infants who presented to our emergency department between March 1990 and July 1991. All symptomatic patients and all infants who did not undergo radiologic evaluation were excluded from the analysis. During the study period, 35 asymptomatic infants were evaluated in our emergency department following head trauma. The mean age of the study patients was 5.5 +/- 3.8 months; 54% were male; and falls accounted for the injury in 88% of cases. The skull radiograms were normal in 30 patients, equivocal in two, and positive for a parietal skull fracture in three. The three infants who sustained skull fractures were male, were younger than three months, and had fallen from heights not exceeding three feet. Computed head tomograms revealed no intracranial pathology in these patients. We conclude that all infants who present following minor skull trauma should undergo radiologic evaluation. PMID- 1454640 TI - Pediatric Emergency Medicine Fellowship survey: 1991-1992. AB - This study was designed to determine the general characteristics, training expectations, and career goals of those individuals entering Pediatric Emergency Medicine Fellowships in 1992 through the NRMP Pediatric Emergency Medicine Match. A 20-item questionnaire was developed and sent to those individuals who successfully obtained fellowship positions through the 1991-1992 Match. All of the respondents will have completed a formal pediatric residency program, and 90% will have completed their residency since 1990. Eighty-eight percent of the respondents have not completed formal postgraduate training other than a pediatric residency, and none of the respondents were from training programs in emergency medicine. Ninety percent of the respondents are planning on two years of training, while 10% are either entering a three-year program or planning an optional third year. Ninety-four percent of the individuals who responded had not applied for Pediatric Emergency Medicine Fellowships in the past, but, while many of the individuals were concerned about obtaining a position, only 6% applied for a fellowship in an alternative field. If the respondents had not obtained positions this year, 79% felt that they would have reapplied next year. When asked why they are pursuing a Pediatric Emergency Medicine Fellowship, 85% listed opportunities in clinical medicine as their primary reason, while 10% claimed that research opportunity was the most important factor. When their fellowships are completed, 77% hope to practice at a university-based children's hospital, and 10% hope to practice at a private children's hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454641 TI - Plastic bronchitis: an unusual cause of respiratory distress in children. AB - This case illustrates an unusual cause of respiratory distress in the pediatric population. A high degree of suspicion is necessary to make the diagnosis of plastic bronchitis. Wheezing and cough will lead to the diagnosis of reactive airway disease and/or foreign body aspiration. Chest radiographs may yield additional information, but the diagnosis is made by bronchoscopy and removal of the casts. Any child with severe respiratory distress refractory to aggressive conventional medical therapy and with a history or radiograph suggestive of plastic bronchitis should be considered a candidate for bronchoscopy. As clinicians, we must always remember the dictum, "All that wheezes is not asthma." PMID- 1454642 TI - Anomalous left coronary artery masquerading as infantile bronchiolitis. AB - Four infants less than six months of age with anomalous left coronary artery from the pulmonary artery who present with symptoms of wheezing are described. All had cardiomegaly on chest radiographs and because of wheezing received beta-agonist agents (albuterol alone or with epinephrine). One developed cardiopulmonary collapse secondary to supraventricular tachycardia after administration of these agents. The literature is reviewed for utility of chest radiographs in infants presenting with wheezing and for the efficacy of beta-adrenergic agents in infants less than six months of age. The authors suggest that physicians have a low threshold for obtaining a chest radiograph prior to treating a first-time wheezing infant less than six months of age with a beta-agonist agent. PMID- 1454643 TI - Thermal epiglottitis after swallowing hot tea. AB - Acute infectious epiglottitis in children is a well-recognized clinical entity. We report the development of acute thermal epiglottitis after ingestion of hot tea by a three-year-old patient. Clinical and radiographic findings in our patient and others reported in the literature resemble acute infectious epiglottitis. In all cases of burns around the mouth, the possibility of intraoral and respiratory damage must be considered. Because of the high risk of upper airway obstruction, children in whom thermal epiglottitis is suspected should be observed in the intensive care unit and have appropriate airway management. PMID- 1454644 TI - Testicular torsion versus epididymitis: a diagnostic challenge. AB - Unlike the patient who presents with a potentially acute abdomen, the child or adolescent with a potentially acute scrotum cannot simply be observed. If testicular torsion is present, the testicle must be detorted and orchiopexy performed as soon as possible for fertility to be maintained. Torsion of the appendix testis, however, can usually be managed without surgery. Since the presentations of epididymitis and testicular torsion overlap, it is sometimes difficult to rapidly make the correct diagnosis. Early genitourinary consultation is appropriate in this setting. Any patient in whom testicular torsion is strongly considered should undergo immediate exploratory surgery without diagnostic studies. If the findings overlap, immediate testicular radionuclide scanning should be arranged; alternatively, with experience, Doppler sonography can be carried out. If these radiographic studies cannot be arranged and interpreted within one to two hours, scrotal exploration should be performed. Any patient with an acute scrotal complaint and a negative scan should receive daily follow-up until the symptoms subside. Although our adolescent patient did well, his acute presentation and findings should have warranted immediate exploration. It is only through this aggressive approach that we can continue to increase testicular salvage rates. PMID- 1454645 TI - Injuries associated with child safety seat misuse. AB - The charts of 370 children under the age of two years who presented to a pediatric emergency department between September 1988 and August 1989 were reviewed. Twenty-seven patients (7% of the total) had injuries associated with child safety seat (CSS) misuse. Thirteen were infants and toddlers injured as motor vehicle occupants when improperly restrained--CSS harness not properly connected (8), use of an improper device (3), and CSS not anchored to the car seat (2). Fourteen were infants under one year of age who were injured falling in their CSS. Injuries included minor head trauma (17), linear skull fracture (5), concussion (1), femoral fracture (1), depressed skull fracture with epidural hematoma (1), cervical vertebral fracture (1), and intraventricular hemorrhage (1). Nine patients were hospitalized. Injuries associated with CSS misuse may be more common than previously recognized and can result in significant injury. Educational efforts should focus on correct usage. PMID- 1454646 TI - Grunting respirations: chest or abdominal pathology? AB - A large percentage of misdiagnosed appendicitis cases occur during childhood. Misdiagnosed patients have increased morbidity and mortality from the diagnostic delay. The patients excused from an emergency facility who are ultimately shown to suffer from appendicitis have higher rates of perforation with attendant abscess formation, peritonitis, sepsis, and potential death. The patients with misdiagnosed appendicitis are young and likely to have atypical signs and symptoms. Grunting respirations incorrectly attributed to respiratory infection may serve as a pathway for a misdiagnosed case of appendicitis. PMID- 1454647 TI - Acute-onset vomiting in a 15-day-old infant. PMID- 1454648 TI - A four year old with a slow heart rate. PMID- 1454649 TI - Aseptic meningitis. PMID- 1454650 TI - Case 01-1992: an 11-year-old boy with fever and a painful hip. PMID- 1454651 TI - Aeromedical transport services and AAP guidelines: a commentary. PMID- 1454652 TI - Seizures associated with meningitis. PMID- 1454653 TI - Management of asthma. PMID- 1454654 TI - [Lysozyme activity in undiluted and diluted blood of patients treated with cyclosporin A with prednisone or azathioprine with prednisone after kidney transplantation]. AB - It is a general opinion that the renal transplant patients may show the decrease of immunity which manifests by their increased susceptibility to bacterial, viral and fungal infections. One of the important non-specific defensive factors of the organism participating in the protection against infections is lysozyme. It is the purpose of the present paper to estimate the lysozyme activity in the un- and diluted serum in the renal transplant patients and to determine the possible mechanism of the observed deviations. 32 renal transplant patients (24 men and 8 women) aged of 16 up to 50 were investigated, being in the period of 1 until 4 years after transplantation. In the investigation the kind of immunosuppressive treatment used was considered which served the purpose of dividing the total group of patients into two subgroups: one treated with cyclosporine (12 patients) and the other treated with azathioprine (20 patients). The control group consisted of 20 healthy persons, matching by age, sex and living place the group investigated. In both groups investigated and control, were determined: lysozyme activity in the serum of the undiluted and diluted blood, total leukocyte number, the absolute number of peripheral blood neutrophils as well as their adherence to fibres was evaluated. In the renal transplant patients compared with the control group and in the separated subgroups, no statistically significant differences were found concerning leukocyte count, absolute neutrophil count and adherence of those cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454655 TI - [Erythropoietin level in the blood of patients with diabetes mellitus type 2]. AB - 52 patients with diabetes mellitus type II (23 of them were treated by diabetic diet, 12 were on oral antidiabetic drugs and 17 were treated by insulin), and in 31 healthy subjects the serum concentrations of erythropoietin (EPO), ferritin, iron, TIBC and hematocrit value, haemoglobin concentration and erythrocytes were measured. In diabetic patients higher but in insulin treated patients significantly higher plasma erythropoietin concentrations were found than in healthy subjects. In diabetic patients the physiological negative correlation between plasma erythropoietin concentration, haematocrit value, haemoglobin concentration and erythrocytes respectively was absent. In diabetic patients plasma ferritin concentrations were significantly higher than in normals. CONCLUSION: patients with diabetes mellitus type II are characterized by elevated plasma erythropoietin and ferritin concentrations and dissociation of the physiological feedback between plasma erythropoietin and intensity of erythropoiesis. PMID- 1454656 TI - [Inhibition of growth hormone (GH) response to GHRH in diabetes mellitus type 1 after blockade of the cholinergic system with pirenzepine]. AB - The effect of pirenzepine, a peripheric cholinergic antagonist, on GHRH-induced GH secretion was studied in 10 type I diabetic subjects and 8 healthy controls. GH response was significantly greater in diabetics than in the healthy controls (p < 0.02) with peak values of 59.6 and 15.9 ng/ml, respectively. Pirenzepine 20 mg in given 15 min before GHRH inhibited GH response in both groups. In diabetics GH response calculated as area under curve (AUC) was inhibited from 3666 to 260 ng/ml. min (p < 0.001) and in the controls from 831 to 255 ng/ml. min (p < 0.05). The great efficacy of pirenzepine in inhibiting GH hypersecretion in type I diabetes may find a clinical application in future. PMID- 1454657 TI - [Comparison of the effectiveness of budesonide and prednisone in the maintenance treatment of pulmonary sarcoidosis]. AB - The aim of this investigation was to compare inhaled budesonide vs oral prednisone in the maintenance phase treatment of pulmonary sarcoidosis. Double blind controlled study was performed in 40 patients with stage II or III pulmonary sarcoidosis. After initial systemic 6 weeks treatment with prednisone (40 reduced to 20 mg daily) patients were allocated either to systematically (P) or topically (B) treated group. P patients continued with 10 mg prednisone daily, B patients were given inhaled budesonide 1.6 mg daily. The progress of treatment was assessed by serial radiography, spirometry, serum ACE activity and plasma cortisol levels. All patients completed the 12 months treatment. Using a numerical score to assess changes on the chest radiograms P patients improved by 1.7 +/- 0.66 points; B patients improved by 1.15 +/- 0.81 points. Spirometric changes were insignificant. Serum ACE fell from 107 +/- 51 U/L in the P group and 92 +/- 40 U/L in the B group to 46 +/- 11 U/L and 38 +/- 21 U/L respectively during the initial phase of treatment. In the maintenance phase ACE levels remained lower than initial ones in both groups. Morning cortisol plasma levels studied in 10 patients (5 in each group) decreased significantly during the initial phase. Thereafter cortisol levels remained low in the P patients returning to the lower limit of normal values in the B patients. We conclude that inhaled budesonide may be a safe and effective alternative to oral steroids in the maintenance treatment of pulmonary sarcoidosis especially in the early, stage II, disease. PMID- 1454658 TI - [Vitamins and arteriosclerosis]. PMID- 1454659 TI - [Disorders of tubular transport of uric acid leading to hyperuricemia]. PMID- 1454660 TI - [Proliferation and differentiation of cells and differentiation- inducing treatment in leukemia]. PMID- 1454661 TI - [Diabetic nephropathy. I. Pathomorphology and pathogenesis]. PMID- 1454662 TI - [Diabetic nephropathy. II. Clinical course and treatment]. PMID- 1454663 TI - Long-term prognosis after myocardial infarction. Who is at risk for sudden death? AB - Patients who have survived myocardial infarction may be at risk for recurrent infarction or sudden death within the first year. Clinical factors that identify high-risk patients include the following: Poor left ventricular function Presence of spontaneous ventricular ectopy Abnormal signal-averaged electrocardiogram Decreased heart rate variability Exercise-induced depression of the ST segment Inducible ventricular tachyarrhythmia When these high-risk patients are identified, appropriate strategies (eg, use of antiarrhythmic agents or an implantable cardioverter-defibrillator) may improve outcome. PMID- 1454664 TI - Acute confusional state. Don't mistake it for dementia. AB - Acute confusional state is a condition that is commonly encountered in many types of medical practice. Certain patients, especially the elderly, are vulnerable to the disorder, and recognition of this fact can help prevent the development or minimize the severity of the condition. Thorough history taking and evaluation often point to the underlying cause, and attention to general principles of environmental and pharmacologic management can minimize morbidity. PMID- 1454665 TI - Management of ascites in patients with cirrhosis. What to do when diuretics fail. AB - Resistant or refractory ascites is unusual in cirrhotic patients who comply with dietary sodium restriction and optimal diuretic therapy. Patients unresponsive to medical therapy often have end-stage liver disease and renal insufficiency, although reversible complicating factors must be excluded. For patients with truly refractory ascites, liver transplantation is the only option that improves chances of survival. When this is not feasible, therapeutic paracentesis is the procedure of choice for intractable ascites. Several surgical shunts have been used, but none have been found to be safer and more effective than large-volume paracentesis. PMID- 1454666 TI - Listerial meningitis. Which patients are vulnerable? AB - The physician's index of suspicion for infection with Listeria monocytogenes should be elevated if a patient presents with symptoms of meningitis and has impaired cell-mediated immunity. Although diagnosis is aided by detection of an elevated white blood cell count and protein level in the cerebrospinal fluid, it requires isolation of the organism from the cerebrospinal fluid. Appropriate antibiotic treatment leads to recovery in most cases. PMID- 1454668 TI - Dear President Clinton. PMID- 1454667 TI - Community-acquired pneumonia. The changing picture. AB - Important changes in the initial management of community-acquired pneumonia have been prompted by the discovery of new respiratory pathogens, the changing susceptibility of traditional pathogens to antimicrobial agents, and the introduction of new antimicrobial agents. Although the clinical presentation may suggest a specific pathogen, findings overlap too much to reliably distinguish the specific cause of the pneumonia on a clinical basis. Useful laboratory studies include Gram's stain and culture of sputum, blood culture, serologic studies, and new tests such as the urinary antigen test for Legionella pneumophila. Empirical antimicrobial treatment must take into consideration that 20% to 30% of cases of community-acquired pneumonia are due to atypical pathogens that are not susceptible to beta-lactam agents. PMID- 1454669 TI - Radiocontrast-induced nephropathy. Prevention is better than cure. AB - The principal predisposing factor in radiocontrast-induced nephropathy appears to be underlying renal insufficiency. Identifying patients at risk is of paramount importance when a diagnostic study is being chosen. Contrast-reliant studies should be avoided, if possible, in high-risk patients. If challenge with a contrast medium is essential, appropriate risk stratification and adequate patient preparation should be done beforehand. Ultimately, prevention is a better approach than cure. PMID- 1454670 TI - The impact of CLIA. PMID- 1454671 TI - The impact of CLIA. PMID- 1454672 TI - Hypothermia. Saving patients from the big chill. AB - Although hypothermia is a serious and sometimes fatal condition, prompt recognition and institution of appropriate rewarming techniques may save even profoundly affected persons. The diagnosis of hypothermia should be considered when patients present with alterations of cerebral function without apparent explanation, especially in the presence of underlying predisposing illnesses and conditions. When hypothermia is suspected, an accurate core temperature must be obtained. Application of rewarming techniques appropriate to the degree of hypothermia may be lifesaving. Conservative use of pharmacotherapy is warranted. PMID- 1454673 TI - Ovarian cancer screening. The search for cost-effective methods. AB - The search goes on for an effective screening test for ovarian cancer. This deadly disease has eluded attempts at early detection with the currently available methods. Dr Williams examines the research regarding various screening methods and suggests areas of promise for future study. PMID- 1454674 TI - Cardiac imaging after acute myocardial infarction. Identification of patients at continued risk. AB - Diagnostic imaging performed early in the course of acute myocardial infarction provides anatomic and functional information that is useful in assessing patients at risk for future cardiac events and premature death. Early identification of left ventricular dysfunction or complications of myocardial infarction allows appropriate and timely management of high-risk patients and early transfer of stable patients from the intensive care environment. Noninvasive predischarge functional imaging to unmask patients with jeopardized myocardium identifies high risk patients who may need invasive studies and surgical or interventional treatment. Postdischarge risk stratification with diagnostic imaging provides vital prognostic information in high- and low-risk patients, allowing for appropriate allocation of medical resources. PMID- 1454675 TI - Selection for body weight at eight weeks of age. 20. Production traits and the B and C alloantigen systems. AB - The current study evaluated influence of genotypes of the B and C alloantigen systems on production traits in lines of White Plymouth Rock chickens. Lines had been selected previously for high (HWS) or low (LWS) 8-wk BW and after 27 generations of selection, a random sample of each selected line was used to initiate subpopulations in which selection was relaxed. For the present study, blood typing was used to identify allelic frequencies for the B and C systems for five consecutive generations of selection (Generations 30 through 34) and three consecutive generations of relaxation (Generations 5 through 7). Haplotypes for the B complex were assigned designations B32, B33, B34, and B35 and alleles of the C system were assigned C8, C9, C10, and C11. Production traits for males were BW at 4 and 8 wk of age, and for females were BW at 4, 8, and 38 wk of age, age and BW at production of first egg, percentage of normal eggs, and percentage of normal hen-day egg production. There were no differences in production traits among B genotypes or among C genotypes, although some time trends in gene frequencies suggested that more subtle effects may be present. PMID- 1454676 TI - Effects of genetic strain and light management on the reproductive performance of turkeys. AB - The laying performance of six genetic strains of turkeys, which have been bred and maintained at the Ohio Agricultural Research and Development Center, Wooster, OH, was compared under three laying house lighting regimens over a period of 3 yr. Light Treatment 1 (L1) consisted of 14 h of continuous light (L) and 10 h of dark (D; 14L:10D) throughout the laying period. Treatment 2 (L2) consisted of 14 h of intermittent light (IL, 15 min L and 45 min D/h) followed by 10 h of continuous dark. The IL treatment was started following a period (6 wk) in which the hens were trained to use the trapnests. Thus, during the first 6 wk of their laying period, L2 hens were also provided 14L:10D. Treatment 3 (L3) hens were provided the same program as L1 for the first 14 wk of the laying period. They were then moved to a continuous period of 19L:5D for the remainder of the laying period. All eggs produced were recorded through 180 days after the first egg was laid. Traits studied included: the number of days to first egg after light stimulation; the number of eggs produced through 84, 120, and 180 days after the first egg was laid; the average clutch length; the maximum clutch length; the total days lost to broodiness; the rate of lay; and the effective length of the laying period. Highly significant differences (P less than or equal to .01) were observed among the strains used for all traits measured. Light treatments showed no significant effects on any trait measured. Thus, from the present studies, the delayed IL program provides an economically attractive management program for environmentally controlled turkey breeder houses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454677 TI - Growth, body composition, and plasma androgen concentration of male broiler chickens subjected to different regimens of photoperiod and light intensity. AB - Day-old male Hubbard broilers (960) were assigned to one of four treatments (two pens of 120 birds per treatment) to evaluate the effects of high (150 lx) versus low (5 lx) light intensity and constant 23 h light (L):1 h dark (D) versus increasing (6L:18D increasing 4 h/wk to 23L:1D) photoperiod in a 2 x 2 factorial arrangement of treatments. Birds were raised to 8 wk on a typical commercial four diet program. Low-intensity birds were heavier than high-intensity birds from 2 to 8 wk (3.25% heavier at 8 wk). Birds raised under constant photoperiod were heavier than birds raised under increasing photoperiod from 2 to 5 wk and at 7 wk of age (1.71% heavier at 7 wk). High-intensity bird carcasses had lower percentage body fat, weight of fat, and higher percentage body protein at 8 wk compared with low-intensity bird carcasses (7.77, 10.76, and 1.77%, respectively). High-intensity birds had smaller abdominal fat pads (weight and percentage of body weight) at 8 wk compared with low-intensity birds (15.46 and 12.17%, respectively). Photoperiod did not affect body composition. Birds treated with increasing photoperiod had larger testes (weight and percentage of body weight) at 8 wk compared with birds under the constant photoperiod (29.36 and 30.51%, respectively). Birds treated under increasing photoperiod had higher plasma androgen concentrations at 7 wk compared with birds under constant photoperiod (testosterone, .270 versus .188 ng/mL; androstenedione, .632 versus .494 ng/mL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454678 TI - Beak trimming and sex effects on behavior and performance traits of large white turkeys. AB - The effects of beak trimming at day old on performance and behavioral activities of male and female Large White turkeys were evaluated. One hundred and twenty poults of each sex were evenly assigned to 20 treatment pens and evaluated for body weight, feed usage, and livability characteristics to 18 wk of age. Behavioral observations were conducted for feeding, drinking, sleeping, huddling, resting, and agonistic activities. Beak trimming affected body weight and feed usage levels for the sexes differently. From 6 wk, trimmed males were significantly heavier than untrimmed males, whereas untrimmed females were heavier than trimmed females from 12 wk. Similar to body weights, feed usage levels from 13 to 18 wk were higher for trimmed males compared with untrimmed males and lower for trimmed females compared with untrimmed females. Feed conversion ratios after 12 wk and survival to 18 wk were not affected by trimming treatment. Livability rates, however, were lowest for untrimmed males and highest for untrimmed females. Effects on behavioral activities were confined primarily to the brooding and early rearing phases. Beak trimming reduced feeding activity of females and drinking activity of both males and females during the first 2 wk. Sleeping, huddling, and resting activities were increased by beak trimming for both sexes during brooding. Agonistic acts were reduced by beak trimming main effect at 3 and 6 wk. Trimmed males committed fewer agonistic acts at 6 wk than untrimmed males. PMID- 1454679 TI - Long segmented filamentous organisms in broiler chicks: possible relationship to reduced serum carotenoids. AB - Over the past several years, broiler-flocks at the author's laboratory have exhibited low serum carotenoid levels. This phenomenon has not been related to exceptionally low carotenoids in the feed or to known protozoan or viral infections. However, long segmented filamentous organisms (LSFO) have been identified in the pale chicks. An inverse correlation between LSFO counts and serum carotenoid levels was not observed, but prevention of LSFO infection consistently resulted in higher carotenoid values. Young chicks were very susceptible to naturally acquired LSFO infection, but the organisms decreased in number with time and became very difficult to find by the time the chicks were 7 wk old. Segments of LSFO containing endospores were detected in mucosal smears. This observation, along with the extreme ease of natural infection, suggests that LSFO are transmitted by dust-borne spores. Transmission can be prevented by fumigation of housing with formaldehyde vapors. PMID- 1454680 TI - Anticoccidial efficacy and chicken toleration of potent new polyether ionophores. 1. The septamycin relative CP-82,009. AB - The anticoccidial activity of the ionophore CP-82,009 against laboratory isolates of four major species of poultry Eimeria was investigated. Parameters of anticoccidial efficacy that were evaluated were control of lesions and weight suppression. At 4 and 5 ppm, CP-82,009 demonstrated broad-spectrum anticoccidial efficacy in battery trials that was equivalent to reference commercial ionophores. When CP-82,009 was fed to uninfected broiler chickens at efficacious dose levels, growth rate and feed efficiency were found to be equivalent to commercial agents over a 21-day period in batteries and over a 49-day period in floor pens. From the present studies, it appears that CP-82,009 is an efficacious anticoccidial that is well tolerated by chickens, and that it ranks among the most potent anticoccidial ionophores described to date. PMID- 1454681 TI - Anticoccidial efficacy and chicken toleration of potent new polyether ionophores. 2. The portmicin relative CP-84,657. AB - The current study investigated the anticoccidial activity of the ionophore CP 84,657 against laboratory strains of the five major pathogenic species of Eimeria that infect poultry. Based on lesion scores and weight gain, the ionophore CP 84,657 achieved broad-spectrum anticoccidial efficacy in battery trials at doses of 4 and 5 ppm that was equivalent to reference commercial ionophores. In uninfected chickens, 4 ppm of CP-84,657 was the highest dose that gave growth rate and feed efficiency equivalent to commercial agents over 21 days in batteries and 49 days in floor pens. Ionophore CP-84,657 is an efficacious, well tolerated anticoccidial in chickens, with potency comparable to that of the most potent known ionophores. PMID- 1454682 TI - Colostrum from cows immunized with Eimeria acervulina antigens reduces parasite development in vivo and in vitro. AB - Experiments were undertaken to determine whether passive immunization utilizing hyperimmune bovine colostrum (HBC) specific for Eimeria acervulina (EA) antigens conferred protection against coccidiosis in chickens. The HBC was produced by immunizing three pregnant, nonmilking Jersey cows with EA antigens administered via one intramuscular injection followed by three intramammary infusions at approximately 10, 8, 6, and 4 wk before parturition. One cow was immunized with sporozoites (SZ), the second with merozoites (MZ), and the third with recombinant merozoite antigen (rMZ). A fourth cow, unimmunized, provided normal colostrum (NC) for control purposes. Colostral whey from each cow was tested by ELISA for antibody against SZ, MZ, and rMZ antigens. In all immunized cows, antiparasite titers were elevated above those of the control. Antibodies from MZ- and rMZ immunized cows recognized both MZ and rMZ antigen. Separate groups of 2-wk-old chickens received two oral doses of anti-SZ, -MZ, or -rMZ HBC or NC or PBS daily from 1 day before through 6 days after oral inoculation (DAI) with EA oocysts. Feces from each group were examined for oocysts. Intestines were examined for lesions 6 DAI. Histologic sections of duodenum were examined for asexual stages and gametocytes utilizing monoclonal antibody and fluorescence microscopy. In Experiments 1 and 2, oocyst production was reduced in all HBC-treated groups, except one treated with rMZ HBC, compared with PBS- or NC-treated groups. In Experiment 2, the severity of lesions was significantly reduced in all HBC treated groups compared with those that received NC or PBS. Significantly fewer developmental stages were found in histological sections from all chickens treated with anti-SZ and anti-rMZ HBC than from controls. Anti-SZ HBC significantly reduced the number of intracellular SZ found 24 h after their inoculation into cultures of primary chicken kidney cells. These results suggest that HBC specific for certain EA antigens can inhibit parasite development and reduce severity of parasite-related gut lesions. PMID- 1454683 TI - Preferential accumulation of n-3 fatty acids in the brain of chicks from eggs enriched with n-3 fatty acids. AB - Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid in the phospholipids of brain tissue. The extent to which maternal dietary n-3 fatty acid may influence the n-3 fatty acid composition of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) fractions of brain and liver tissue of progeny was investigated. Hens were fed diets containing n-9, n-3, or n-6 fatty acids. The brain tissue of the chicks from eggs enriched with n-3 fatty acids contained higher DHA, resulting in an increased C22:6 n-3:C20:4 n-6 ratio compared with chicks from eggs enriched with n-9 or n-6 fatty acids. Incorporation of C22:5 n 3, and C22:6 n-3 was mainly in the PE fraction as compared with the PC fraction of the chick brain. For chicks hatched from eggs enriched with n-9, n-3, and n-6 fatty acids, the total n-3 fatty acids in the brain PE fraction were 29.3, 41.3, and 21.9% compared with 6.7, 8.8, and 4.0% in the brain PC fraction. In contrast, the n-3 fatty acids increased evenly in phospholipid PC and PE fractions. Total amounts of PE in the brain lipids of chicks from eggs enriched with n-3 and n-6 fatty acids were 40.8 and 41.9% compared with 33.1% for chicks from eggs enriched with n-9 fatty acids. Analyses of the remaining yolk sac revealed a preferential absorption of DHA from the egg PE fraction by the developing chick. PMID- 1454684 TI - Growth, thyroid function, and serum macromineral levels in magnesium-deficient chicks. AB - Growth and thyroid function were studied in Mg-deficient chicks. Dietary levels of 80 to 315 ppm Mg were compared with control levels of 578 to 787 ppm Mg. Signs of Mg deficiency appeared rapidly and acutely within 2 to 5 days at dietary levels of 250 to 260 ppm or lower. Growth and feed intake decreased progressively as the deficiency became more severe. Control chicks pair-fed with the deficient chicks gained significantly more weight. Serum Mg decreased at all levels of Mg below control, but at 260 and 315 ppm it returned to control values after 21 days on treatment. Serum Ca diminished only when dietary Mg was 250 ppm or less. Serum K increased in severely deficient chicks but decreased over time in milder deficiencies. Thyroid gland weights were unchanged. However, very young chicks fed a Mg-deficient diet had lower serum 3,5,3'-triiodothyronine (T3) whereas serum thyroxine (T4) was generally unaffected. Beyond 1 wk of age chicks that had prior access to a Mg-sufficient diet had low serum T4 levels whereas serum T3 was unchanged. Therefore, peripheral thyroid hormone metabolism is altered in a Mg deficiency, but this effect is dependent on the age at which the deficiency occurs. PMID- 1454685 TI - The effect of early protein restriction (zero to eight weeks) on skeletal development in turkey toms from two to eighteen weeks. AB - Turkey toms were fed protein- and lysine-deficient diets or protein- and lysine adequate diets from 0 to 4 and 5 to 8 wk and similar diets from 9 to 18 wk. Beginning at 2 wk of age and at approximate 2-wk intervals thereafter, the length and width of the right tibia were measured in nine toms per treatment. The length and width of the femur were measured beginning at 8 wk. Three tibiae that were close to the average length for each age and treatment were selected for ashing. The top 25% (epiphyseal) and middle 10% (diaphyseal) segments from each of these bones were fat-extracted prior to ashing. Mean length of the tibia continued to increase throughout the experiment whereas tibia width reached a plateau at 16 wk. Femur length also continued to increase throughout the study whereas there were no significant changes in femur width after 16 wk. Compared with the control diet, the diet deficient in protein and lysine resulted in a significant decrease in tibia and femur width at all ages. There were no dietary effects on tibia length at 16 and 18 wk, however. There were no significant dietary effects on femur length after 14 wk. There were significant age effects but no significant dietary effects on epiphyseal or diaphyseal bone ash. Epiphyseal bone ash increased from 41 to 54% over the course of the study whereas diaphyseal bone ash increased only from 59 to 64%. PMID- 1454686 TI - 2-Hydroxy-4 (methylthio) butanoic acid as a drinking water supplement for broiler chicks. AB - Two experiments were conducted to study the effects on chick performance of a commercially available liquid methionine analog [2-hydroxy-4 (methylthio) butanoic acid; HMB] supplied through drinking water. Methionine activities of .025 and .05% were added to drinking water and compared with levels of .03, .06, or .09% included in a low-methionine basal diet from 0 to 21 days of age. Mortality was not significantly altered by any dietary treatment. Neither feed nor water intake was affected adversely by HMB inclusion in drinking water. Only male body weight in Experiment 1 did not respond to HMB feed supplementation. Equivalent levels of total sulfur amino acid intake among water treatments were associated with significantly heavier body weights than the control. In both experiments, body weight and feed efficiency of birds receiving .05% methionine activity as HMB in water were equal or superior to those of groups that received supplemented feed. The results indicate that, under the study conditions, HMB provided in drinking water can be effectively assimilated by broiler chicks, at least through 21 days of age. PMID- 1454687 TI - Effect of heating on nutritional quality of conventional and Kunitz trypsin inhibitor-free soybeans. AB - Five 10-day chick growth experiments and an amino acid digestibility assay were conducted to assess the effect of steam heating on in vivo protein quality of raw, full-fat Kunitz trypsin inhibitor-free soybeans (KFSB) compared with raw, conventional full-fat soybeans (CSB). Protein solubility in .2% KOH was also evaluated as an in vitro test of in vivo protein quality for underprocessed CSB. The CSB and KFSB were autoclaved for 0, 3, 6, 9, 12, 15, 18, or 21 min at 121 C and 124 kPa. The soybeans were then fed to 8- or 9-day-old chicks as the sole source of protein in dextrose and soybean diets containing 23% protein. Growth performance of chicks fed raw KFSB was superior to that of chicks fed raw CSB. Growth performance of chicks fed autoclaved KFSB or CSB increased and pancreas weight (percentage of body weight) decreased as autoclaving time increased. Slightly less autoclaving time was consistently required to achieve maximum chick performance for KFSB compared with CSB. Less autoclaving time was also required to obtain maximum digestibility of amino acids in KFSB compared with CSB. Urease activity of the soybeans decreased as autoclaving time increased, whereas protein solubility in .2% KOH for CSB did not change consistently in response to heating time. The results of the present study indicate that raw KFSB must be heated to obtain maximum protein quality for chicks and that protein solubility in KOH is not a sensitive indicator of underprocessing of CSB soybeans. PMID- 1454688 TI - The effect of enzyme supplementation on the apparent metabolizable energy and nutrient digestibilities of wheat, barley, oats, and rye for the young broiler chick. AB - The influence of enzyme supplementation on the bioavailable energy (AME(n)) and apparent digestibilities of lipid (ALD) and protein (APD) in young broiler chicks was examined for diets containing either wheat, hulled or hulless barley, naked oats, or spring rye. Dietary AME(n), APD, and ALD values were depressed (P less than or equal to .01) for all test grains (except hulled Bedford barley) as the inclusion rate of the grain replacing wheat increased. The antinutritives, beta glucans (barley and oats) and pentosans (rye), had the most pronounced effect on ALD. The decreases in ALD were 43, 77, and 67% for chicks fed diets containing 70% Scout barley (hulless), Terra oats, and Gazelle rye, respectively, compared with those fed the control wheat diet. Enzyme supplementation increased (P less than or equal to .01) AME(n), APD, and ALD for all test cereals. The corresponding increases in the AME(n), of the enzyme-supplemented diets containing 70% HY320 wheat, Bedford barley, Scout barley, Terra oats, and Gazelle rye diets were 4, 7, 42, 33, and 14%, respectively, compared with their unsupplemented counterparts. Enzyme treatment also improved (P less than or equal to .01) weight gains and feed conversion efficiencies of chicks fed diets containing each of the cereals. Overall, the results demonstrate that the nutritive value of cereal grains such as wheat, barley, oats, and rye can be improved by the addition of crude fungal extracts to the diet of young chicks. PMID- 1454689 TI - Ionic and endocrine characteristics of reproductive failure in calcium-deficient and vitamin D-deficient laying hens. AB - Whole blood ionized calcium and plasma total calcium, inorganic phosphorus, estradiol-17 beta, progesterone, and 1,25-di-hydroxycholecalciferol concentrations were measured in calcium- or vitamin D-deficient Single Comb White Leghorn hens. Control birds were serially sampled every 2 h for 26 h immediately following oviposition until the next oviposition. Deficient birds, which had ceased laying 10 to 14 days prior to sampling, were sampled at the same times. The control birds had significantly higher mean total and bound plasma calcium and inorganic phosphorus concentrations than the deficient hens. Control and vitamin D-deficient hens had similar mean ionized calcium concentrations. Control hens exhibited a cyclic pattern in ionized calcium and inorganic phosphorus concentrations over the sampling period that was related to shell calcification. Deficient hens showed no changes in ionized calcium concentration during this time. Plasma 1,25-dihydroxycholecalciferol concentrations were significantly higher in the calcium-deficient birds than the control or vitamin D-deficient hens. Mean plasma estradiol-17 beta and progesterone concentrations were consistently higher in the control hens than the deficient hens. Consistent with this observation were decreases in ovary and oviduct weights, which occurred in the nonlaying deficient hens. PMID- 1454690 TI - Effect of dietary supplemental pyridoxine levels on the hatchability of turkey eggs. AB - Two identical experiments were conducted each with 120 Large White turkey hens in individual cages to determine the value of dietary pyridoxine supplementation for increasing hatchability. The hens were fed a basal corn and soybean meal diet. Weekly data responses were averaged across 5- to 6-wk timespans and recorded in three grouped time periods over the reproduction cycles. The hens were photostimulated at 31 wk of age and at 33 wk of age were assigned to dietary treatments containing 0, 6, 12, and 18 mg of supplemented pyridoxine/kg of diet. Thirty hens were fed each dietary treatment. In Experiment 1, eggs were collected for 4 days in the middle of each time period and egg yolk and albumen were assayed separately for vitamin B6. Although the vitamin B6 concentration in egg yolk was stable (1.9 micrograms/g dried basis), concentrations of vitamin B6 in egg albumen increased with incremental dietary pyridoxine levels; however, the average level of vitamin B6 in egg albumen was only 4% of the average level in egg yolk. About 37 micrograms of vitamin B6 per egg (82 g) was assayed in eggs from all treatments in the production periods. Incremental dietary levels of supplemented pyridoxine above the basal (unsupplemented pyridoxine) diet level did not result in increasing hatchability or egg vitamin B6 levels. Differences were not observed for 7-day or 28-day embryo deaths among treatments within the three 5- or 6-wk production periods of both experiments. PMID- 1454691 TI - Effect of feed allowance during rearing and breeding on female broiler breeders. 1. Growth and carcass characteristics. AB - The influence of feed allowance on growth and carcass characteristics was investigated with female Indian River broiler breeders. Four feeding programs were imposed: FF, provided ad libitum access to feed throughout; FR, provided ad libitum access to feed from 0 to 18 wk of age and restricted thereafter; RF, provided ad libitum access to feed from 0 to 4 wk, restricted from 4 to 18 wk, and consumed feed ad libitum thereafter; RR, provided ad libitum access to feed from 0 to 4 wk of age and restricted thereafter. All birds received a starter diet (2,739 kcal ME/kg, 19.1% CP) from 0 to 3 wk of age, a grower diet (2,729 kcal ME/kg, 15.5% CP) from 3 to 22 wk of age, and a layer diet (2,889 kcal ME/kg, 14.6% CP) from 22 to 62 wk of age. Restricted feeding (limited amount, fed daily) was based on commercial BW guidelines. Feed restriction (37.2% of ad libitum intake) during rearing (4 to 18 wk) slowed growth. At 18 wk of age, restricted birds (RF, RR) had an average BW of 1.9 kg and a shank length of 9.2 cm compared with ad libitum-fed birds (FF, FR), which had an average BW of 4.2 kg and a shank length of 10.8 cm. Despite the large difference in BW, percentage carcass protein did not differ significantly between the two rearing treatments; however, percentage carcass fat was almost four times greater in ad libitum-fed than in feed-restricted birds. The growth deficit remained significant to 62 wk of age in RF birds compared with FF birds. During the prebreeding period (18 to 23 wk), feed intake of RF birds was 209% that of RR birds and 133% that of FF birds. At sexual maturity, the BW of RF birds was 3.6 kg, compared with 4.6, 4.5, and 2.6 kg for FF, FR, and RR birds, respectively. Stepwise regression indicated that BW was the most important (R2 = .363, P = .0001) among 11 variables in determining the number of large (greater than 10 mm) follicles in the ovaries of breeders at sexual maturity. PMID- 1454692 TI - Effect of feed allowance during rearing and breeding on female broiler breeders. 2. Ovarian morphology and production. AB - The influence of feed allowance during rearing (4 to 18 wk) and breeding (18 to 62 wk) on ovarian morphology and egg production was examined. During rearing, beginning at 4 wk of age, 400 Indian River pullets that had been full-fed from 1 day of age either continued to be full-fed (F, n = 200) or were feed restricted (R, n = 200), following commercial practice. At 18 wk of age, 100 birds (within +15% of the mean BW) in each of F and R rearing groups were further assigned to be full-fed (n = 50) or feed restricted (n = 50) during breeding. Thus, based on feed allowance during rearing and breeding, four treatment groups were formed (FF, FR, RF, and RR). Feed restriction during rearing significantly delayed oviduct development and age at sexual maturity (age at first egg). Compared with feed restriction during both rearing and breeding (RR), ad libitum feeding beginning at 18 wk of age (RF) significantly increased the weight of the ovary and the number of large follicles at sexual maturity but did not significantly affect the age at sexual maturity. Feed restriction during rearing, breeding, or both significantly reduced the incidence of erratic ovipositions, defective eggs, and multiple ovulations. The incidence of erratic ovipositions was positively correlated (r = .692, P less than or equal to .001) with the laying of soft shelled and shell-less eggs and negatively correlated (r = -.508, P less than or equal to .001) with the production of settable eggs to 62 wk of age. Compared with ad libitum feeding, controlled feeding during breeding significantly improved both settable and total egg production. Among the four feeding regimens, Treatment RR resulted in the highest fertility and hatchability. PMID- 1454693 TI - Effect of feed allowance during rearing and breeding on female broiler breeders. 3. Ovarian steroidogenesis. AB - The influence of feed allowance during rearing (4 to 18 wk) and breeding (18 to 62 wk) on in vitro follicular steroidogenesis was examined. Four feeding programs were imposed: FF, consumed feed ad libitum throughout; FR, provided ad libitum access from 0 to 18 wk of age and restricted thereafter; RF, provided ad libitum access to feed from 0 to 4 wk, restricted from 4 to 18 wk, and consumed feed ad libitum thereafter; RR, consumed feed ad libitum from 0 to 4 wk of age and restricted thereafter. All birds received a starter diet (2,739 kcal ME/kg, 19.1% CP) from 0 to 3 wk of age, a grower diet (2,729 kcal ME/kg, 15.5% CP) from 3 to 22 wk of age, and a layer diet (2,889 kcal ME/kg, 14.6% CP) from 22 to 62 wk of age. Restricted feeding was based on commercial guidelines. At 33 wk of age, 10 to 12 (FF = 10, FR = 12, RF = 10, and RR = 11) birds from each feeding regimen were killed by cervical dislocation and the follicles removed for in vitro steroidogenesis. Feed allowance during breeding (18 to 62 wk) had a significant effect on in vitro follicular steroidogenesis at 33 wk of age. In broiler breeders fed ad libitum, some of the F2 (second largest) follicles had an endocrine profile characteristic of the F1 (largest) preovulatory follicles, secreting very little androstenedione and large amounts of progesterone. In feed restricted birds, only the F1 follicles, which were destined to ovulate next, secreted any significant amount of progesterone into the culture media. Compared with restricted feeding, ad libitum feeding significantly increased the production of androstenedione in small white follicles (less than 1 mm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1454694 TI - Post-mortem biochemistry of Pekin duckling and broiler chicken Pectoralis muscle. AB - Biochemical post-mortem changes between red and white avian muscle were determined using duckling and chicken Pectoralis muscles, respectively. Six live Pekin ducklings and six live broiler chickens, in each of two trials, were obtained from commercial plants and processed at a pilot facility. After evisceration, carcasses were held at 4 C, then Pectoralis muscles were removed at .25, 1, 4, and 24 h post-mortem, and sampled for pH, lactate, adenosine triphosphate (ATP) content, and R-value (inosine to adenine ratio). Duckling Pectoralis pH significantly (P less than .05) decreased from 6.25 to 5.66 from .25 to 24 h post-mortem, respectively, as compared with that of the chicken, which decreased from 6.41 to 5.62 for the same times. Duckling lactate values, from .25 to 24 h, increased from 15.86 to 28.86 mumol/g, respectively, and chicken lactate values increased from 27.62 to 53.51 mumol/g. The ATP content of the duckling Pectoralis muscle decreased from 1.59 to .14 mumol/g and chicken Pectoralis decreased from 3.42 to .21 mumol/g from .25 to 24h, respectively. The R-values of duckling and chicken Pectoralis significantly increased from .25 to 24 h (.98 to 1.37 and .80 to 1.51, respectively). Duckling and chicken biochemical measurements were significantly different at all post-mortem sampling times, except for 24-h values of pH (5.66 versus 5.62, respectively) and 24-h contents of ATP (.14 versus .21 mumol/g, respectively). The different post-mortem biochemical measurements between duckling and chicken Pectoralis muscle is evidence that different rates of post-mortem metabolism and rigor development exist between these red and white avian breast muscles. PMID- 1454695 TI - Research note: in ovo administration of a competitive exclusion culture treatment to broiler embryos. AB - Exposure of chicks to salmonellae in the hatchery and hatchery environment limits the effectiveness of a competitive exclusion (CE) culture treatment. Therefore, in an attempt to apply treatment before chicks are exposed to salmonellae, the CE culture was introduced in ovo to unhatched embryos. An undefined, anaerobically grown CE culture, derived from cecal contents of healthy adult chickens, was diluted 1:1,000 or 1:1,000,000 and inoculated either into the air cell or beneath the inner air cell membrane of 17-day-old incubating hatching eggs. The treated chicks were more resistant than untreated chicks to varying challenge levels of Salmonella typhimurium, indicating that it may be possible to initiate protection of chicks to salmonellae challenge prior to hatching into a contaminated environment. PMID- 1454696 TI - A lonely widow with glycosuria. PMID- 1454697 TI - Travellers' health. PMID- 1454698 TI - Arthritis and infections. PMID- 1454699 TI - Managing miscarriage. PMID- 1454700 TI - Recurrent miscarriage. PMID- 1454701 TI - Occupational lung diseases. PMID- 1454702 TI - Treating paediatric malignancies. PMID- 1454703 TI - Examples from the orals. PMID- 1454704 TI - Snoring and obstructive sleep apnoea. PMID- 1454705 TI - Sore throats and URTIs. PMID- 1454706 TI - The chronically discharging ear. PMID- 1454707 TI - Otitis media--antibiotics or not? PMID- 1454708 TI - Extended-wear contact lenses. PMID- 1454709 TI - A question of payment. PMID- 1454710 TI - A request for slimming tablets. PMID- 1454711 TI - Planning an immunisation schedule. PMID- 1454712 TI - Hepatitis A vaccination. PMID- 1454713 TI - Diagnosis of mouth lesions. PMID- 1454714 TI - Diagnosis of depression. PMID- 1454715 TI - Stress and mental health. PMID- 1454716 TI - Imaging in three dimensions. PMID- 1454717 TI - The MRCGP examination. PMID- 1454718 TI - Medical records. PMID- 1454719 TI - Selecting staff. PMID- 1454720 TI - Developing staff skills. PMID- 1454721 TI - Staff training and appraisal. PMID- 1454722 TI - Prescribing policies. PMID- 1454723 TI - ACE inhibitors in heart failure. PMID- 1454724 TI - HRT and audit circles. PMID- 1454725 TI - Coronary disease is grossly under investigated. PMID- 1454726 TI - Not every patient with angina requires coronary angiography. PMID- 1454727 TI - Preventing pregnancy in Down's syndrome. PMID- 1454728 TI - Illnesses from abroad. PMID- 1454729 TI - Prostate cancer. PMID- 1454730 TI - Psychosomatic illness in children. PMID- 1454731 TI - The Employment Medical Advisory Service. PMID- 1454732 TI - Fertility and infertility. PMID- 1454733 TI - Gynaecological cancer. PMID- 1454734 TI - Management of menorrhagia. PMID- 1454735 TI - Surgical treatment of menstrual disorders. PMID- 1454736 TI - Sexual problems. PMID- 1454737 TI - Effective treatment of depression. PMID- 1454738 TI - Prescribing in heart disease. PMID- 1454739 TI - Home or hospital birth? PMID- 1454740 TI - Shoplifting by a menopausal woman. PMID- 1454741 TI - Imported malaria. PMID- 1454742 TI - Health and safety in the surgery. PMID- 1454743 TI - Psychopathic and violent patients. PMID- 1454744 TI - GPs, social workers and the Mental Health Act. PMID- 1454745 TI - Manic-depressive disorder. PMID- 1454746 TI - Schizophrenia in general practice. PMID- 1454747 TI - Why bother with a practice formulary? PMID- 1454749 TI - Effects of endosulfan and aldrin on muscle coordination and conditioned avoidance response in rats. AB - The deteriorative effects after chronic endosulfan exposure on muscle coordination, learning and memory of rats were compared with that produced by aldrin which has been reported to have similar effects in experimental animals. A rota-rod apparatus was used to study the muscle coordination and learning and memory were tested by recording the response to unconditioned and conditioned stimuli using a pole-climbing apparatus. Aldrin but not endosulfan inhibited motor coordination in both sexes. A greater motor deterioration occurred in male group. This finding, together with the previous data which shows inhibition by its metabolite of motor activity, suggests that its metabolic product is responsible for this action. Like aldrin, endosulfan inhibited both learning ability and conditioned avoidance response. A change in the activities of brain monoamines or inhibition of perception and reflexes or both were proposed for these behavioural effects, since the former was reported to be produced by both compounds and the latter was found to occur in aldrin treated rats. PMID- 1454748 TI - Could the pharmacological differences observed between angiotensin II antagonists and inhibitors of angiotensin converting enzyme be clinically beneficial? AB - Over the past several years, angiotensin I converting enzyme (ACE) inhibitors, compounds that block the formation of angiotensin II (ANG II), have become widely used in the treatment of cardiovascular disease. Recently, a new class of orally active, non-peptide inhibitors of the renin-angiotensin system, the ANG II receptor antagonists have also become available. Since both classes of compounds block the renin-angiotensin system, although at different sites, it remains to be determined whether blockade of ANG II receptors will have any specific advantage over inhibition of ACE. The following review assesses the actions of ANG II antagonists and suggests ways in which blockade of ANG II receptors may differ both pharmacologically and clinically from inhibition of ACE. PMID- 1454750 TI - Absence of CYP3A genetic polymorphism assessed by urinary excretion of 6 beta hydroxycortisol in 102 healthy subjects on rifampicin. AB - A previous study has demonstrated that the urinary level of 6 beta hydroxycortisol is a marker of liver CYP3A content after induction by rifampicin. To put in evidence an eventual genetic polymorphism for this cytochrome, the frequency distribution of 6 beta-hydroxycortisol excretion was investigated in 102 healthy Caucasians before and after 6 days of oral rifampicin administration (600 mg daily). After rifampicin treatment, a wide interindividual distribution was observed but no clear bimodality. Moreover the mean 6 beta-hydroxycortisol level was higher in women (n = 38) than in men (n = 64). These observations do not favour the existence of a CYP3A genetic polymorphism based on 6 beta hydroxycortisol excretion but evoke a sexual dimorphism. However, CYP3A is composed of at least four enzymes and as the enzyme(s) responsible for cortisol 6 beta-hydroxylation is (are) not perfectly known, it can not be excluded that a genetic polymorphism does exist for one enzyme of this family. PMID- 1454751 TI - Extrahepatic disposition of 3H-aflatoxin B1 in the rainbow trout (Oncorhynchus mykiss). AB - Whole-body autoradiography in rainbow trout (Oncorhynchus mykiss) after oral and intravenous administration of 3H-labelled aflatoxin B1 showed labelling of several extrahepatic tissues, such as the uveal melanin and the vitreous humour of the eyes, the trunk and head kidney, the olfactory rosettes and the pyloric caecae. Liquid chromatography of extracts of the vitreous humour showed that unmetabolized 3H-AFB1 was the main labelled material present at this site. Liquid chromatography of extracts of the uveal melanin showed presence of aflatoxicol and aflatoxin B1 in proportions of about 3:1. The binding to the pigment is probably due to a hydrophobic type of interaction with the melanin. Microautoradiography showed that melanin-containing cells in the trunk and head kidney and in the olfactory rosettes also accumulated high amounts of radioactivity. In the trunk kidney there was, in addition, a labelling of the second segment of the proximal tubules and of the distal tubules and the collecting ducts. Studies in vitro with microsomal and 12,000 x g supernatant preparations of the trunk kidney showed formation of DNA- and protein-bound metabolites from the aflatoxin B1. It is probable that the bioactivation of the aflatoxin B1 is confined to the cytoplasm of the cells, may be related to excretion and/or absorption processes. Microautoradiography of the olfactory rosettes, showed labelling of the sensory epithelium, but not the indifferent epithelium. A low formation of protein-bound aflatoxin B1-metabolites was found in incubations with microsomal preparations of this tissue. The same observation was made in incubations with microsomal preparations of the head kidney. In the pyloric caeca bound metabolites were observed in vivo at a level comparable to that found in the trunk kidney. Our results suggest that retention and metabolism in some extrahepatic tissues might be of importance as concerns the toxicologic potential of aflatoxin B1 in the rainbow trout. PMID- 1454752 TI - Effect of antioxidants on hypoxia/reoxygenation-induced injury in isolated perfused rat liver. AB - Isolated perfused livers from rats fasted overnight were subjected to 30 min. of hypoxia followed by reoxygenation for 60 min., resulting in marked cytotoxicity as evidenced by an enhanced release of cytosolic enzymes (lactate dehydrogenase: 14-fold over controls, glutamate-pyruvate-transaminase: 12-fold over controls) and glutathione (twofold over controls) into the perfusate, by calcium accumulation (by a factor of 1.4) in the tissue and by an 80% inhibition of bile secretion. Virtually no mitochondrial injury became apparent and no evidence for lipid peroxidation could be found. In the presence of ascorbate, an augmentation of hepatic injury was observed. This might be due to the pro-oxidant activity of ascorbate in the presence of ionized iron, which is easily released from high molecular weight stores under reductive (e.g. hypoxic) conditions. The water soluble vitamin E analogue trolox C as well as propyl gallate clearly protected the liver against hypoxia/reoxygenation injury, yielding further evidence for a causative role of oxidative stress in this model. Due to their water solubility and their high efficacy as free radical scavengers, these antioxidants might be of therapeutic value. PMID- 1454753 TI - Acute neurobehavioural effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Han/Wistar rats. AB - The neurobehavioural effects of a single non-lethal dose (1000 micrograms/kg intraperitoneally) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were assessed in young male Han/Wistar rats, highly resistant to acute lethality of TCDD. TCDD decreased body weight significantly compared with ad libitum fed controls. TCDD did not change the behaviour or the motility of rats in the open field test 8 days after the treatment nor did it affect the spontaneous motor activity up to 27 days after the exposure. In the elevated plus-maze test for anxiety, TCDD treated rats did not differ from either ad libitum fed controls or pair-fed controls. In the 24-hr passive avoidance test, the learning of TCDD-treated rats did not differ significantly from that of ad libitum fed controls or pair-fed controls from 8 hr to 16 days after the treatment. TCDD did not affect the motor coordination or the maintenance of balance on the rotating rod but it impaired them slightly in the elevated horizontal bridge test 16 hr after exposure. It did not affect nociception in the hot plate test 16 hr or 8 days after the injection. The results suggest that a single sublethal dose of TCDD does not alter markedly the general behaviour of Han/Wistar rats, in contrast to its striking effect on feeding behaviour which results in a marked decrease in body weight gain. PMID- 1454754 TI - Lipid peroxidation of erythrocyte membrane induced by lipoamide dehydrogenase in the presence of ADP-Fe3+. AB - Lipid peroxidation of rat erythrocyte membranes was induced by lipoamide dehydrogenase (LADH) (EC 1.8.1.4) in the presence of ADP-Fe3+. Superoxide dismutase (SOD) (EC 1.15.1.1) strongly inhibited the peroxidation reaction but catalase did not. Hydroxyl radical scavengers, mannitol and dimethylsulfoxide did not inhibit the lipid peroxidation. These results indicated that the lipid peroxidation was a superoxide (O2-)-dependent reaction, but the hydroxyl radical was not involved. ADP-Fe3+, in the presence of LADH, was reduced more rapidly under aerobic than anaerobic conditions and SOD under aerobic conditions strongly inhibited the iron reduction, indicating that O2- plays a predominant role in iron reduction. Hydrogen peroxide enhanced O2- generation by LADH, but the peroxidation reaction was not affected. In the presence of lipoamide, lipid peroxidation was also induced but the reactions were not inhibited by SOD. Evidently, the lipid peroxidation induced in the presence of lipoamide was O2(-) independent. Dihydrolipoamide may be involved in the peroxidation reaction. PMID- 1454755 TI - Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations. AB - Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean +/- S.D.) values following single dose administration of Cardil and Cardizem were 678.4 +/- 321.5 and 948.6 +/- 580.6 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.89 and 0.44 1.34 respectively. At steady-state a significant difference between Cmax/Cmin and tmax was seen Cmax/Cmin being 4.9 and 3.2 respectively and Tmax being 2.7 +/- 2.0 and 6.0 +/- 2.8 hr respectively, whereas Cmax and AUC did not differ significantly. The AUC (mean +/- S.D.) values in steady state of Cardil and Cardizem were 880.1 +/- 399.8 and 1056.8 +/- 509.8 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.96 and 0.66-1.26 respectively. Although the observed ratios AUCCardil/AUCCardizem in both the single-dose and the steady-state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2). PMID- 1454756 TI - ["...what tumors actually are..." On the history of microscopic cancer diagnosis]. PMID- 1454757 TI - [Pigmented villonodular synovitis--a review with reference to 166 cases]. PMID- 1454758 TI - [New pathohistologic WHO classification of salivary gland adenomas]. PMID- 1454759 TI - [An institution-specific autopsy register]. PMID- 1454760 TI - [Risk of cancer following cholecystectomy, hysterectomy or appendectomy]. AB - Patients with previous cholecystectomy, hysterectomy or appendectomy have an increased risk of developing cancer of other organs such as the bowel, breast kidney or ovary, particularly if they have undergone more than one operation. Previous nephrectomy, strumectomy, prostatectomy or gastric resection for gastroduodenal ulcer do not increase the risk of bowel cancer. PMID- 1454761 TI - [Normal values of myocardial thickness of both heart ventricles in infants and young children]. PMID- 1454762 TI - [Achille Chereau's dictum of the ovary and Rudolf Virchow's postulate of virilismus ovarioprivus]. PMID- 1454763 TI - [Presentation of the heart in the works of Niels Stensen and Andreas Vesal]. PMID- 1454764 TI - [Determining the significance of antineutrophil cytoplasmic autoantibodies]. PMID- 1454765 TI - [A program for medical use of information systems. Validity of calculation of direct costs for the initial treatment of acute myeloblastic leukemia]. AB - In order to validate the information systems medicalization program used since 1984 at the Hotel-Dieu hospital, Paris, the direct costs given by this program were compared with those calculated from the medical records of 10 adult patients hospitalized for diagnosis and treatment of acute myeloblastic leukaemia. The mean direct cost of an 8 to 81 days hospital stay was estimated at 75.393 +/- 41.260 French francs by the program and 84.969 +/- 52.288 FF by calculations from the records. A fairly good correlation (r2 = 0.72; P = 0.002) was found between the 2 evaluations. There was no statistically significant difference between the figures obtained by the 2 methods, except for pharmaceutical expenditures (P = 0.005) which were grossly underevaluated by the program. A better correlation could be obtained if an attribution of drugs and transfusions per patient was entered in the program. PMID- 1454766 TI - [Gastroesophageal reflux treated by posterior hemifundoplication. 251 cases]. AB - Between September 1983 and March 1991, 251 consecutive patients with gastro oesophageal reflux resistant to medical treatment underwent posterior hemifundoplication (modified Toupet procedure). One hundred and seventy-seven patients (71 percent) had peptic oesophagitis. pH monitoring showed a mean Kaye's score of 278 +/- 245 with a 29 percent part of total recording time at pH < 4. The mean low oesophageal sphincter pressure was 8.5 +/- 6.5 cm H2O. No patient died in the postoperative period. Morbidity consisted of 8 splenic injuries, as well as 8 pulmonary and 23 thromboembolic complications. Assessment of 199 patients (79 percent) with a mean follow-up of 32 +/- 21 months showed complete symptomatic relief in 96.5 percent, and complete endoscopic healing of oesophagitis was noted in 96 percent. Restoration of the pH profile to normal levels was obtained in 86 percent of the cases. The mean low oesophageal sphincter pressure had risen to 17 +/- 6 cm H2O. Early postoperative dysphagia was noted in 46 patients (18 percent); one of them required reoperation. Reflux symptoms persisted in 9 patients (4.5 percent). pH monitoring revealed abnormal levels in 3 patients. The results of this study demonstrate that effective gastro oesophageal reflux control can be achieved with the modified Toupet procedure. PMID- 1454767 TI - [Inflammatory pseudotumor of the urachus. A case]. AB - The occurrence in a 9-year old boy of a painful, prominent and solid mid hypogastric tumour is reported. This clinically isolated muscular tumour was suggestive of sarcoma. En bloc resection of the tumour including the attached vesical cupula was performed. Histology showed that this large tumour was purely inflammatory and had developed from remnants of the urachus. This diagnosis must be considered whenever a suprapubic tumour is discovered. Since malignant transformation of urachus cysts is possible, surgical resection is advised. PMID- 1454769 TI - [Nephrotic syndrome caused by Plasmodium malariae infection. A case with favourable outcome]. PMID- 1454768 TI - [Atrial natriuretic factor in heart insufficiency]. AB - The atrial natriuretic factor is a peptide with vasodilator and natriuretic properties which is synthesized and released by atrial myocytes. In patients with chronic heart failure the ventricles contribute to the synthesis of this peptide, so that its plasma concentration rises in proportion to the heart filling pressure. The atrial natriuretic factor, therefore, seems to be a good biological marker of functional and haemodynamic severity of heart failure. However, the weight of this factor in the neuro-hormonal balance has not yet been fully evaluated, owing to the usual attenuation of its biological effects. This, and the necessity of continuous parenteral administration limits, for the moment, its therapeutic applications. Inhibitors of the enzyme involved in its metabolism are being tested, but only preliminary results are available in humans. PMID- 1454770 TI - [Thyroid pseudo-nodule revealing cervicofacial actinomycosis]. PMID- 1454771 TI - [Celiosurgical gonadectomy for Morris' syndrome. A case]. PMID- 1454772 TI - [Idiopathic infarction of a sigmoid fatty fringe. Two cases diagnosed and treated by celiosurgery]. PMID- 1454773 TI - [Acquired subglottic stenosis after heart-lung transplantation. Efficacy of treatment by inhalation of budesonide]. PMID- 1454774 TI - [Hepatitis C virus antibodies. Seroprevalence in HIV infected patients]. PMID- 1454775 TI - [Prolonged isolated fever revealing angiosarcoma]. PMID- 1454776 TI - [Atherosclerosis of the aortic arch. A source of cerebral embolism?]. PMID- 1454777 TI - [Brucella vaccination in professionally exposed subjects. Prospective study]. AB - This prospective phase IV study on cohort concerns a vaccine made of the phenol insoluble fraction of Brucella abortus biotype 1 (B19 strain). Three hundred and three professionally exposed subjects entered the study; 161 out of 182 subjects (88.5 percent) with negative response to an intradermal test for detection of previous contamination accepted to be vaccinated. Booster injections were given 18 and 36 months after vaccination. Local pain was observed after 45.2 percent of injections and moderate systemic reactions after 5 percent of injections. Seropositivity after primary vaccination reached 80 percent. The booster injection, justified by a major decrease of this rate after 18 months, gave exactly the same response of the thymo-independent type. This vaccinal schedule did not result in detectable hypersensitivity. The clinical effectiveness of the vaccine could not be evaluated accurately because of the insufficient number of subjects. The possibility of subclinical infection in vaccinated subjects calls for wider comparative studies of vaccinated versus non-vaccinated subjects. PMID- 1454778 TI - [Plasma beta chorionic gonadotropin between 14 and 20 weeks of amenorrhea: a sign of pregnancy-related hypertension]. AB - A defect of placenta maturation has been described in hypertension of pregnancy. Plasma beta chorionic gonadotropins (beta HCG) of placental origin rise at the onset of pregnancy and reach a peak between 9 and 10 weeks of amenorrhoea. As we were making systematic assays between 14 and 20 weeks in a trisomy detection programme, we looked for differences in plasma beta HCG levels between women with pregnancy-induced arterial hypertension and pregnant women with normal blood pressure. We also studied the predictive value of such assays. Pregnancy-induced hypertension was found in 6 women in a population of 89 nulliparas and in 12 women in a population of 163 multiparas. beta HCG levels were significantly higher in women who later developed hypertension among both nulliparas (52,833 +/ 19,538 IU vs 24,499 +/- 16,485 IU) and multiparas (50,558 +/- 23,597 IU vs 20,911 +/- 11,677 IU). In nulliparas, taking 43,000 IU as threshold of pathology we found that the predictive value of beta HCG was higher than that of other tests which had gone through controlled studies (sensitivity 67 percent, specificity 91.6 percent, positive predictive value 36 percent, negative predictive value 97.4 percent, relative risk 5.4). In multiparas, taking 38,000 as threshold and combining this marker with obstetrical history it was possible to predict the occurrence of hypertension more precisely than with other markers which had gone through controlled studies (sensitivity 66.7 percent, specificity 98 percent, positive predictive value 61.4 percent, negative predictive value 97.3 percent, relative risk 8.4). PMID- 1454779 TI - [Deforming arthropathy associated with the presence of anti Jo-1 antibody in polymyositis. A new case]. AB - A deforming arthropathy confined to the hands developed in a woman with polymyositis of three year's duration. Roentgenograms showed distal subluxations of several fingers, especially the thumb, asymmetrical marginal erosions of the phalanges and periarticular calcifications. These roentgenographic findings are considered to be specific of polymyositis associated with anti-Jo-1 antibody. PMID- 1454780 TI - [Hemolytic and uremic syndrome revealing myelodysplasia in a child]. PMID- 1454781 TI - [Celiosurgery: beware of antimist sprays! A new septic risk]. PMID- 1454782 TI - [Late onset Plasmodium falciparum malaria revealed by corticoid therapy]. PMID- 1454783 TI - [Neisseria mucosa meningitis after intradural infiltration]. PMID- 1454784 TI - [Are zinc and selenium markers of progression in HIV infected patients?]. PMID- 1454786 TI - Gene therapy. PMID- 1454785 TI - Sp1 and the subfamily of zinc finger proteins with guanine-rich binding sites. PMID- 1454787 TI - Implicit knowledge: new perspectives on unconscious processes. AB - Recent evidence from cognitive science and neuroscience indicates that brain damaged patients and normal subjects can exhibit nonconscious or implicit knowledge of stimuli that they fail to recollect consciously or perceive explicitly. Dissociations between implicit and explicit knowledge, which have been observed across a variety of domains, tasks, and materials, raise fundamental questions about the nature of perception, memory, and consciousness. This article provides a selective review of relevant evidence and considers such phenomena as priming and implicit memory in amnesic patients and normal subjects, perception without awareness and "blindsight" in patients with damage to visual cortex, and nonconscious recognition of familiar faces in patients with facial recognition deficits (prosopagnosia). A variety of theoretical approaches to implicit/explicit dissociations are considered. One view is that all of the various dissociations can be attributed to disruption or disconnection of a common mechanism underlying conscious experience; an alternative possibility is that each dissociation requires a separate explanation in terms of domain specific processes and systems. More generally, it is concluded that rather than reflecting the operation of affectively charged unconscious processes of the kind invoked by psychodynamic or Freudian theorists, dissociations between implicit and explicit knowledge are a natural consequence of the ordinary computations of the brain. PMID- 1454788 TI - Application of DNA fingerprinting to the recovery program of the endangered Puerto Rican parrot. AB - The Puerto Rican parrot was reduced to approximately 13 animals in 1975 and as a conservation measure, a captive population was established from a few founders taken from the wild between 1973 and 1983. The number of successful breeding pairs in captivity has been low, and the captive breeding program has not been as productive as that of the closely related Hispaniolan parrot. Therefore, a genetic study was initiated to examine the relative levels of relatedness of the captive founders using levels of bandsharing in DNA fingerprints. Unrelated captive founder Puerto Rican parrots had the same average level of bandsharing (0.41) as second-degree relatives of the Hispaniolan parrot (0.38, P > 0.05), with an inbreeding coefficient of 0.04. High levels of bandsharing (> 40%) between pairs of males and females correlated with reproductive failure, suggesting that inbreeding depression is partly responsible for the low number of breeding pairs. Consequently, DNA profiling can be used to guide the captive breeding program for the Puerto Rican parrot, and other endangered species, by identifying pairs of males and females with low levels of bandsharing. PMID- 1454789 TI - Requirement for coenzyme Q in plasma membrane electron transport. AB - Coenzyme Q is required in the electron transport system of rat hepatocyte and human erythrocyte plasma membranes. Extraction of coenzyme Q from the membrane decreases NADH dehydrogenase and NADH:oxygen oxidoreductase activity. Addition of coenzyme Q to the extracted membrane restores the activity. Partial restoration of activity is also found with alpha-tocopherylquinone, but not with vitamin K1. Analogs of coenzyme Q inhibit NADH dehydrogenase and oxidase activity and the inhibition is reversed by added coenzyme Q. Ferricyanide reduction by transmembrane electron transport from HeLa cells is inhibited by coenzyme Q analogs and restored with added coenzyme Q10. Reduction of external ferricyanide and diferric transferrin by HeLa cells is accompanied by proton release from the cells. Inhibition of the reduction by coenzyme Q analogs also inhibits the proton release, and coenzyme Q10 restores the proton release activity. Trans-plasma membrane electron transport stimulates growth of serum-deficient cells, and added coenzyme Q10 increases growth of HeLa (human adenocarcinoma) and BALB/3T3 (mouse fibroblast) cells. The evidence is consistent with a function for coenzyme Q in a trans-plasma membrane electron transport system which influences cell growth. PMID- 1454791 TI - Active complete in vitro replication of nodavirus RNA requires glycerophospholipid. AB - Flockhouse virus (FHV) is a member of the nodavirus group of positive-strand RNA viruses. In the absence of additional compounds, a template-dependent RNA dependent RNA polymerase extracted from FHV-infected cells synthesizes complementary (-)-strand copies of added FHV RNA to yield a double-stranded RNA product. Upon addition of glycerophospholipid (GPL), this system reproducibly carries out complete highly active replication of added FHV RNA, producing newly synthesized (+)-strand RNA in predominantly single-stranded RNA form. This accounts for previously observed effects of Lipofectin (a mixture of GPL and cationic lipid) in the system. All tested neutral and negatively charged GPLs except phosphatidic acid support complete FHV RNA replication in this in vitro system, as do phospholipid extracts from uninfected and FHV-infected cells. Neither sphingomyelin, a membrane phospholipid that is not derived from glycerol, nor cholesterol supported FHV RNA replication. Testing of compounds derived from GPL shows that the ability of active GPL to support FHV (+)-strand RNA synthesis is dependent on the structures of both the head group and the acyl chains. Neither the phosphorylated head group nor the diacylglycerol lipid moiety alone supports RNA replication. The length and saturation of acyl chains strongly influence the ability of GPL to support RNA replication. Other characteristics of this in vitro RNA replication system and the possible role played by membranes and their components in FHV RNA replication are discussed. PMID- 1454790 TI - A putative ATP-dependent RNA helicase involved in Saccharomyces cerevisiae ribosome assembly. AB - We have isolated a cold-sensitive mutant of Saccharomyces cerevisiae in which there is a deficit of 60S ribosomal subunits. Cold sensitivity and the assembly defect are recessive and cosegregate, defining a single essential gene that we designated DRS1 (deficiency of ribosomal subunits). The wild-type DRS1 gene was cloned by complementation of the cold-sensitive phenotype of drs1. Sequence analysis reveals a high degree of similarity to a family of proteins that are thought to function as ATP-dependent RNA helicases. Pulse-chase analysis of ribosomal RNA synthesis and processing indicates that the drs1 mutant accumulates the 27S precursor of the mature 25S rRNA. These results suggest that, as in pre mRNA splicing, RNA helicase activities are involved in ribosomal RNA processing. PMID- 1454792 TI - Evidence that the packaging signal for nodaviral RNA2 is a bulged stem-loop. AB - Flock house virus is an insect virus belonging to the family Nodaviridae; members of this family are characterized by a small bipartite positive-stranded RNA genome. The larger genomic segment, RNA1, encodes viral replication proteins, whereas the smaller one, RNA2, encodes coat protein. Both RNAs are packaged in a single particle. A defective-interfering RNA (DI-634), isolated from a line of Drosophila cells persistently infected with Flock house virus, was used to show that a 32-base region of RNA2 (bases 186-217) is required for packaging into virions. RNA folding analysis predicted that this region forms a stem-loop structure with a 5-base loop and a 13-base-pair bulged stem. PMID- 1454793 TI - At least three distinct proteins are necessary for the reconstitution of a specific multiprotein complex at a eukaryotic chromosomal origin of replication. AB - We have reconstituted in vitro a multistage assembly of a protein complex that specifically recognizes a yeast genomic origin of replication, the autonomously replicating sequence ARS121. The first step in the assembly was the interaction of the known origin-binding factor OBF1 and another factor, OBF2, with the ARS121 origin of replication to form the OBF1-OBF2-origin complex. This complex was the substrate for the ATP-dependent binding of a third DNA-binding activity, the core binding factor, CBF. Binding of CBF to the origin, identified by the retarded mobility of the origin DNA fragment in agarose gels, required, in addition to ATP and the OBF1-OBF2-origin complex, a functional essential core nucleotide sequence. ARS121 DNA containing mutations in the core, which inactivate the origin in vivo, did not sustain stable CBF binding, whereas ARS121 DNA mutated outside the boundaries of the essential core, which has normal origin function, bound CBF as wild type. This tight, direct correlation between the ability of the origin to bind CBF and its function as an origin of replication in vivo strongly suggest that the multiprotein complex reconstituted in vitro has a key role in the initiation of DNA replication. PMID- 1454794 TI - Marked replicative advantage of human mtDNA carrying a point mutation that causes the MELAS encephalomyopathy. AB - The segregation of mutant and wild-type mtDNA was investigated in transformants constructed by transferring human mitochondria from individuals belonging to four pedigrees with the MELAS encephalomyopathy-associated mtDNA mutation (MELAS is mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) into human mtDNA-less (rho 0) cells. Five of 13 clonal cell lines containing mixtures of wild-type and mutant mtDNAs were found to undergo a rapid shift of their genotype toward the pure mutant type. The other 8 cell lines, which included 6 exhibiting nearly homoplasmic mutant mtDNA, on the contrary, maintained a stable genotype. Subcloning experiments and growth rate measurements clearly indicated that an intracellular replicative advantage of mutant mtDNA was mainly responsible for the dramatic shift toward the mutant genotype observed in the unstable cell lines. PMID- 1454795 TI - A yeast cyclophilin gene essential for lactate metabolism at high temperature. AB - The cyclophilins are a family of ubiquitous eukaryotic proteins first identified by high affinity for cyclosporin A (CsA). The immunosuppressant and cytotoxic effects of CsA are thought to result from formation of a toxic complex between cyclophilin and CsA rather than from inhibition of cyclophilin function. The physiological role(s) of the cyclophilins is unknown. Cyclophilins have in vitro peptidylprolyl cistrans isomerase (PPIase) activity, and thus may be involved in protein folding in vivo. We have isolated a yeast cyclophilin gene, CPR3, which encodes a presumptive mitochondrial isoform. While CPR3 disruption mutants lack any phenotype at 30 degrees C, they are unable to grow on L-lactate at 37 degrees C. Disruptions of two other cyclophilin genes (CPR1, CPR2) and of FPR1, the gene encoding an FK506 binding protein with PPIase activity, do not affect growth on L lactate at 37 degrees C. L-Lactate metabolism requires transcriptional induction of CYB2, the gene encoding flavocytochrome b2; cpr3 mutants induce transcription of this gene normally. This result demonstrates a conditional lethal phenotype for a cyclophilin mutation and presents a system for genetic and biochemical analysis of cyclophilin function. PMID- 1454796 TI - Isolation, characterization, and transcription of the gene encoding mouse mast cell protease 7. AB - A gene that encodes mouse mast cell protease (mMCP) 7 (also known as mouse mast cell tryptase 2) was isolated by genomic cloning with a cDNA that encodes mMCP-6, a tryptase in serosal mast cells. cDNAs encoding mMCP-7 were isolated from a bone marrow-derived mast cell cDNA library. The mMCP-7 gene spans 2.3 kilobases and contains five exons rather than six, as found in the mMCP-6 and human mast cell tryptase I genes. Comparison of the 5' end of the transcript with the genomic sequence indicated that the region corresponding to the first intron in the mMCP 6 and human tryptase I genes is not spliced during transcription of mMCP-7 mRNA because of a point mutation at the intron 1 acceptor splice site; this results in a 5' untranslated region of 195 nucleotides, which is longer than that of any other known mast cell-specific transcript. mMCP-7 is 71-76% homologous with mMCP 6 and with dog and human mast cell tryptases, and it is the most acidic mast cell protease, with an overall net charge of -10. RNA blot analyses revealed that the mMCP-7 gene is transcribed in bone-marrow-derived mast cells but is not transcribed in mature serosal mast cells or in mucosal mast cell-enriched intestinal tissue of Trichinella spiralis-infected mice. Transcription of the mMCP-7 gene by differentiating bone-marrow-derived mast cells occurred within 1 week of bone-marrow culture but decreased dramatically after 3 weeks. Thus, the mMCP-7 gene displays a number of unusual structural characteristics and is distinctive in its transient and selective expression in immature mast cells maintained in interleukin 3-enriched medium. PMID- 1454797 TI - Expression of a coriander desaturase results in petroselinic acid production in transgenic tobacco. AB - Little is known about the metabolic origin of petroselinic acid (18:1 delta 6cis), the principal fatty acid of the seed oil of most Umbelliferae, Araliaceae, and Garryaceae species. To examine the possibility that petroselinic acid is the product of an acyl-acyl carrier protein (ACP) desaturase, Western blots of coriander and other Umbelliferae seed extracts were probed with antibodies against the delta 9-stearoyl-ACP desaturase of avocado. In these extracts, proteins of 39 and 36 kDa were detected. Of these, only the 36-kDa peptide was specific to tissues which synthesize petroselinic acid. A cDNA encoding the 36 kDa peptide was isolated from a coriander endosperm cDNA library, placed under control of the cauliflower mosaic virus 35S promoter, and introduced into tobacco by Agrobacterium tumefaciens-mediated transformation. Expression of this cDNA in transgenic tobacco callus was accompanied by the accumulation of petroselinic acid and delta 4-hexadecenoic acid, both of which were absent from control callus. These results demonstrate the involvement of a 36-kDa putative acyl-ACP desaturase in the biosynthetic pathway of petroselinic acid and the ability to produce fatty acids of unusual structure in transgenic plants by the expression of the gene for this desaturase. PMID- 1454798 TI - Fibrinogen blocks the autoactivation and thrombin-mediated activation of factor XI on dextran sulfate. AB - The intrinsic pathway of blood coagulation is activated when factor XIa, one of the three contact-system enzymes, is generated and then activates factor IX. Factor XI has been shown to be efficiently activated in vitro by surface-bound factor XIIa after factor XI is transported to the surface by its cofactor, high molecular weight kininogen (HK). However, individuals lacking any of the three contact-system proteins--namely, factor XII, prekallikrein, and HK--do not suffer from bleeding abnormalities. This mystery has led several investigators to search for an "alternate" activation pathway for factor XI. Recently, factor XI has been reported to be autoactivated on the soluble "surface" dextran sulfate, and thrombin was shown to accelerate the autoactivation. However, it was also reported that HK, the cofactor for factor XIIa-mediated activation of factor XI, actually diminishes the thrombin-catalyzed activation rate of factor XI. Nonetheless, it was suggested that thrombin was a more efficient activator than factor XIIa. In this report we investigated the effect of fibrinogen, the major coagulation protein in plasma, on the activation rate of factor XI. Fibrinogen, the preferred substrate for thrombin in plasma, virtually prevented autoactivation of factor XI as well as the thrombin-mediated activation of factor XI, while having no effect on factor XIIa-catalyzed activation. HK dramatically curtailed the autoactivation of factor XI in addition to the thrombin-mediated activation. These data indicate that factor XI would not be autoactivated in a plasma environment, and thrombin would, therefore, be unlikely to potentiate the activation. We believe that the "missing pathway" for factor XI activation remains an enigma that warrants further investigation. PMID- 1454799 TI - Relationship between O6-alkylguanine-DNA alkyltransferase activity and N-methyl N'-nitro-N-nitrosoguanidine-induced mutation, transformation, and cytotoxicity in C3H/10T1/2 cells expressing exogenous alkyltransferase genes. AB - While a great deal of evidence has directly implicated the importance of O6 alkylation of guanine in the mutagenicity of alkylating agents, evidence demonstrating the oncogenic potential of this lesion has been largely indirect. We have combined a well-studied in vitro neoplastic transformation system (using C3H/10T1/2 mouse cells) with a proven method of gene transfection for expressing the bacterial O6-alkylguanine-DNA alkyltransferase (AT; EC 2.1.1.63) repair genes ada and ogt to generate subclones which possess augmented repair capability toward specific DNA lesions. The products of these genes specifically and differentially repair O6-methylguanine (O6-MeGua), O4-methylthymine (O4-MeThy), and methylphosphotriesters. We show that the level of expression of either the ada or the ogt AT gene in C3H/10T1/2 cells directly correlates with protection against mutation to ouabain resistance by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Subclones expressing 70 fmol of AT per 10(6) cells exhibited a mutation frequency approximately 1/40th of that of clones expressing 15 fmol of AT per 10(6) cells when treated with MNNG at 0.4 micrograms/ml. Protection against mutagenesis by MNNG at 0.8 micrograms/ml, however, did not exceed 12-fold even in subclones expressing greater than 100 fmol of AT per 10(6) cells. As an MNNG dose of 0.6 micrograms/ml was sufficient to saturate more than 95% of the AT activity in any of the clones, the residual mutation frequency may have been caused by unrepaired O6MeGua lesions. In contrast to mutagenesis, protection against neoplastic transformation in vitro, in cells expressing high levels of AT, was most pronounced in cells treated with the highest dose of MNNG used (1.2 micrograms/ml). Low levels of transformation caused by MNNG at 0.4 and 0.8 micrograms/ml were not consistently inhibited in those clones. These data suggest that O6-MeGua formation is of major but not unique significance in the neoplastic transformation of C3H/10T1/2 cells by MNNG. PMID- 1454800 TI - Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides: an in vitro model for treatment. AB - We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) infection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complementary to different regions of HIV-1 RNA, blocked replication of the virus in a sequence-specific manner at 1 microM concentration. Variations in antiviral activity were seen among the different oligonucleotides, revealing an effect of target selection. Mismatched or random oligonucleotide phosphorothioates delayed, but did not completely inhibit, HIV-1 replication. In the case of inhibition by a splice-acceptor-site antisense oligodeoxynucleotide, a break-through phenomenon occurred after 25 days of treatment, suggesting the development of an "escape mutant." This result did not occur when the inhibitory oligodeoxynucleotides were complementary to the primary sequence areas of the rev-responsive element and rev-1 genes. Sequential treatment of HIV-1-infected cells with a combination of different antisense oligonucleotides, each administered once, also prevented the development of escape mutants. Our results suggest that chemotherapy based on specifically targeted antisense-oligonucleotide phosphorothioates may be an effective method for reducing the viral burden in HIV-1-infected individuals at clinically achievable oligonucleotide concentrations. PMID- 1454801 TI - Transcription of the hypersensitive site HS2 enhancer in erythroid cells. AB - In the human genome, the erythroid-specific hypersensitive site HS2 enhancer regulates the transcription of the downstream beta-like globin genes 10-50 kilobases away. The mechanism of HS2 enhancer function is not known. The present study employs RNA protection assays to analyze the transcriptional status of the HS2 enhancer in transfected recombinant chloramphenicol acetyltransferase (CAT) plasmids. In erythroid K562 cells in which the HS2 enhancer is active, the HS2 sequence directs the synthesis of long enhancer transcripts that are initiated apparently from within the enhancer and elongated through the intervening DNA into the cis-linked CAT gene. In nonerythroid HL-60 cells in which the HS2 enhancer is inactive, long enhancer transcripts are not detectable. Splitting the HS2 enhancer between two tandem Ap1 sites abolishes the synthesis of a group of long enhancer transcripts and results in loss of enhancer function and transcriptional silencing of the cis-linked CAT gene. In directing the synthesis of RNA through the intervening DNA and the gene by a tracking and transcription mechanism, the HS2 enhancer may (i) open up the chromatin structure of a gene domain and (ii) deliver enhancer binding proteins to the promoter sequence where they may stimulate the transcription of the gene at the cap site. PMID- 1454802 TI - General splicing factors SF2 and SC35 have equivalent activities in vitro, and both affect alternative 5' and 3' splice site selection. AB - The human pre-mRNA splicing factors SF2 and SC35 have similar electrophoretic mobilities, and both of them contain an N-terminal ribonucleoprotein (RNP)-type RNA-recognition motif and a C-terminal arginine/serine-rich domain. However, the two proteins are encoded by different genes and display only 31% amino acid sequence identity. Here we report a systematic comparison of the splicing activities of recombinant SF2 and SC35. We find that either protein can reconstitute the splicing activity of S100 extracts and of SC35-immunodepleted nuclear extracts. Previous studies revealed that SF2 influences alternative 5' splice site selection in vitro, by favoring proximal over distal 5' splice sites, and that the A1 protein of heterogeneous nuclear RNP counteracts this effect. We now show that SC35 has a similar effect on competing 5' splice sites and is also antagonized by A1 protein. In addition, we report that both SF2 and SC35 also favor the proximal site in a pre-mRNA containing duplicated 3' splice sites, but this effect is not modulated by A1. We conclude that SF2 and SC35 are distinct splicing factors, but they display indistinguishable splicing activities in vitro. PMID- 1454803 TI - Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. AB - Recent demonstrations of survival-promoting activity by neurotrophic agents in diverse neuronal systems have raised the possibility of pharmacological therapy for inherited and degenerative disorders of the central nervous system. We have shown previously that, in the retina, basic fibroblast growth factor delays photoreceptor degeneration in Royal College of Surgeons rats with inherited retinal dystrophy and that the growth factor reduces or prevents the rapid photoreceptor degeneration produced by constant light in the rat. This light damage model now provides an efficient way to assess quantitatively the survival promoting activity in vivo of a number of growth factors and other molecules. We report here that photoreceptors can be significantly protected from the damaging effects of light by intravitreal injection of eight different growth factors, cytokines, and neurotrophins that typically act through several distinct receptor families. In addition to basic fibroblast growth factor, those factors providing a high degree of photoreceptor rescue include brain-derived neurotrophic factor, ciliary neurotrophic factor, interleukin 1 beta, and acidic fibroblast growth factor; those with less activity include neurotrophin 3, insulin-like growth factor II, and tumor necrosis factor alpha; those showing little or no protective effect are nerve growth factor, epidermal growth factor, platelet-derived growth factor, insulin, insulin-like growth factor I, heparin, and laminin. Although we used at least one relatively high concentration of each agent (the highest available), it is still possible that other concentrations or factor combinations might be more protective. Injecting heparin along with acidic fibroblast growth factor or basic fibroblast growth factor further enhanced the degree of photoreceptor survival and also suppressed the increased incidence of macrophages produced by either factor, especially basic fibroblast growth factor. These results now provide the impetus for determining the normal function in the retina, mechanism(s) of rescue, and therapeutic potential in human eye diseases for each agent. PMID- 1454804 TI - Binding and transport of gangliosides by prosaposin. AB - Prosaposin, the precursor of saposins A, B, C, and D, which activate lysosomal hydrolysis of sphingolipids, exists in various tissues and body fluids and is especially abundant in the nervous system. Prosaposin and saposins A,B, C, and D formed stable complexes with 13 different gangliosides as measured by an assay using column chromatography. Gangliosides of the gangliotetraose type (a series) were bound with high affinity, whereas b series gangliosides, O-acetylated gangliosides, and gangliosides with shorter carbohydrate chains, were bound with lower affinity. Prosaposin and saposins transferred gangliosides from donor liposomes to erythrocyte ghost membranes. Prosaposin also stimulated ganglioside GM1 beta-galactosidase more than mature saposins. Prosaposin exists as a secretory protein and as an integral membrane protein, and we propose that prosaposin is active as a ganglioside binding and transport protein in vivo. PMID- 1454805 TI - Basal release of nitric oxide from aortic rings is greater in female rabbits than in male rabbits: implications for atherosclerosis. AB - Estradiol is known to exert a protective effect against the development of atherosclerosis, but the mechanism of this hormonal action is unknown. One of the early events in the development of atherosclerosis is the adhesion of macrophages to endothelial cells, and nitric oxide (NO) inhibits this process. We show that basal release of NO is greater with endothelium-intact aortic rings from female rabbits than those from males. Oophorectomy diminishes both circulating estradiol concentration and basal release of NO to levels seen in male rabbits. These data establish that basal NO release from endothelium-intact aortic rings depends on circulating estradiol concentration and offer an explanation for the protective effect of estradiol against the development of atherosclerosis. PMID- 1454806 TI - Control of gal transcription through DNA looping: inhibition of the initial transcribing complex. AB - Involvement of DNA looping between two spatially separated gal operators, OE and OI, in repression of the gal operon has been demonstrated in vivo. An in vitro transcription assay using a minicircle DNA containing the gal promoter region with lac operators was employed to elucidate the molecular mechanism of repression. Wild-type lac repressors (LacI+ protein molecules), which are capable of associating into a tetramer and forming a DNA loop, repressed transcription from promoter sites P1 and P2, whereas a non-looping lac repressor mutant (LacI(adi)) failed to show normal repression of both of the gal promoters. Thus a DNA loop is also required for repression of transcription in vitro. Repression mediated by DNA looping resulted in the inhibition of the synthesis of complete as well as aborted transcripts, demonstrating that the repressive action was on the formation or activity of the initial transcribing complex. Under similar conditions, the gal repressor (GalR protein) did not repress the gal promoters effectively, apparently because it failed to loop DNA containing gal operators in the purified system. The component(s) or conditions that aid GalR in DNA looping remain to be identified. PMID- 1454807 TI - NAD+ and NADH regulate an ATP-dependent kinase that phosphorylates enzyme I of the Escherichia coli phosphotransferase system. AB - Crude extracts of Escherichia coli contain a protein kinase, EI-K, that phosphorylates enzyme I (EI) of the phosphoenolpyruvate:glycose phosphotransferase system (PTS). Phosphorylation occurs at the active site histidine residue. The activity of EI-K was lost during purification. However, kinase activity was restored by adding NAD+ or NADP+.NADH reversed NAD+ activation of the kinase, and the level of EI-K activity was dependent on the NAD+/NADH ratio. Although crude preparations of EI-K showed no NAD+ requirement, they were completely inhibited by NADH, either in the assay mixture or when the enzyme was pretreated and the NADH was removed prior to the assay. NAD+ restored full activity to the NADH-pretreated inactive fractions. The results suggest that EI-K contains a bound cofactor that is lost during purification and that may be analogous to NAD+. EI-K activity may serve to link some of the diverse functions of the PTS, such as sugar transport, to the metabolic state of the cell. PMID- 1454808 TI - Aerosol gene delivery in vivo. AB - The ability to express transgenes selectively within the lung will greatly facilitate the development of gene therapy for a variety of human diseases. We have demonstrated that aerosol administration of a chloramphenicol acetyltransferase (CAT) expression plasmid complexed to cationic liposomes produces high-level, lung-specific CAT gene expression in mice in vivo. Significant levels of CAT activity are seen in the lungs for at least 21 days following aerosolization. In situ immunostaining for intracellular CAT protein reveals that the majority of airway epithelial and alveolar lining cells are transfected in vivo. Histological analyses show no apparent treatment-related damage. These results have important implications for the development of human gene therapy. PMID- 1454809 TI - Molecular cloning of the gene for the yeast homolog (ACB) of diazepam binding inhibitor/endozepine/acyl-CoA-binding protein. AB - Diazepam binding inhibitor (DBI)/endozepine (EP)/acyl-CoA-binding protein (ACBP) is a small, highly conserved protein which has been independently isolated and characterized from different species using several different biological systems. To further investigate the structural and functional properties of this protein, we have cloned the homologous gene for DBI/EP/ACBP from the budding yeast Saccharomyces cerevisiae. The yeast gene contains no introns and encodes a polypeptide of 87 amino acids (including the initiating methionine), identical in length to the human gene product with 48% conservation of amino acid residues. The most highly conserved domain consists of 7 contiguous residues which are identical in all known protein species from yeast, birds, and mammals. This domain has previously been shown to constitute the hydrophobic binding site on DBI/EP/ACBP for acyl-CoA esters and is located within the second helical region of the molecule. Major and minor mRNA species of approximately 520 and 740 nucleotides, respectively, were detected in exponentially growing yeast. Sequences similar to those implicated in the regulation of fatty acid synthesis and beta-oxidation in yeast were detected in the promoter region of the gene. The presence of a highly conserved DBI/EP/ACBP gene in a primitive organism such as yeast provides support for the basic biological role of DBI/EP/ACBP as an acyl CoA-binding protein and suggests that many of the biological functions attributed to it in higher organisms may result from its ability to interact with acyl-CoA. Hence, we have designated the yeast gene as ACB, for acyl-CoA-binding protein. PMID- 1454810 TI - Yeast RNA polymerase II initiation factor e: isolation and identification as the functional counterpart of human transcription factor IIB. AB - Yeast RNA polymerase II initiation factor e was purified to homogeneity and identified by biochemical criteria as the counterpart of human transcription factor IIB. Factor e was essential for initiation of transcription from yeast and mammalian promoters in a reconstituted yeast transcription system. Activity resided in a single polypeptide of approximately 41 kDa, identified by peptide sequence analysis as the product of the SUA7 gene. Factor e interacted specifically with RNA polymerase II, consistent with a proposed role in determining the start site of transcription. PMID- 1454811 TI - Drosophila homolog of the human S6 ribosomal protein is required for tumor suppression in the hematopoietic system. AB - The tumor suppressor gene lethal(1)aberrant immune response 8 (air8) of Drosophila melanogaster encodes a homolog of the human S6 ribosomal protein. P element insertions that prevent expression of this gene cause overgrowth of the lymph glands (the hematopoietic organs), abnormal blood cell differentiation, and melanotic tumor formation. They also cause delayed development, inhibit growth of most of the larval organs, and lead to larval lethality. Mitotic recombination experiments indicate that the normal S6 gene is required for clone survival in the germ line and imaginal discs. The S6 gene produces a 1.1-kilobase transcript that is abundant throughout development in wild-type animals and in revertants derived from the insertional mutants but is barely detectable in the mutant larvae. cDNAs corresponding to this transcript show a 248-amino acid open reading frame with 75.4% identity and 94.8% similarity to both human and rat S6 ribosomal protein sequences. The results reveal a regulatory function of this ribosomal protein in the hematopoietic system of Drosophila that may be related to its developmentally regulated phosphorylation. PMID- 1454812 TI - Probucol inhibits neointimal thickening and macrophage accumulation after balloon injury in the cholesterol-fed rabbit. AB - Restenosis is a frequent long-term complication after balloon angioplasty. Although smooth muscle cells form the major constituent of the occluding lesion, macrophage-derived foam cells are usually also present in high abundance. The latter have the potential to accelerate the rate of reocclusion because they elaborate many potent cytokines and growth factors, which may act to either recruit cells into the neointima or cause neointimal cell proliferation. Macrophage-derived foam-cell formation depends upon the uptake of modified low density lipoprotein via a scavenger receptor-mediated pathway. Foam-cell formation is accompanied by the release of smooth muscle cell mitogens and chemoattractants. We have examined the effects of probucol, a lipid-soluble antioxidant, in the balloon-catheterized carotid artery of the cholesterol-fed rabbit to evaluate the importance of oxidative processes in restenosis. After 5 weeks, serum cholesterol levels were 32% lower (P < 0.05) in rabbits fed 1% probucol with 2% cholesterol, compared with those receiving cholesterol alone. Probucol inhibited neointimal macrophage accumulation by 68% (P < 0.001), reduced absolute intimal size by 51% (P < 0.05), and reduced the intima/media thickness ratio by 51%. These inhibitory effects were directly related to serum probucol concentrations and appeared to be unrelated to probucol's hypocholesterolemic activity. These data suggest that reactive oxygen species may be involved in the intimal response to injury and that antioxidants, such as probucol, may be therapeutically useful as inhibitors of restenosis. PMID- 1454813 TI - Structural analysis of the human interferon gamma receptor: a small segment of the intracellular domain is specifically required for class I major histocompatibility complex antigen induction and antiviral activity. AB - Mutations of the human interferon gamma (IFN-gamma) receptor intracellular domain have permitted us to define a restricted region of that domain as necessary for both induction of class I major histocompatibility complex antigen by IFN-gamma and protection against encephalomyocarditis virus. This region consists of five amino acids (YDKPH), all of which are conserved in the human and murine receptors. Tyr-457 and His-461 are essential for activity. Approximately 80% of the amino acids of the intracellular domain of the receptor is not required for major histocompatibility complex class I antigen induction or for antiviral protection against encephalomyocarditis virus. The observation that there was no protection by IFN-gamma against vesiculostomatitis virus indicates that other factors, in addition to chromosome 21 accessory factor(s), are required to generate the full complement of transduction signals from the human IFN-gamma receptor. PMID- 1454814 TI - Drug design by machine learning: the use of inductive logic programming to model the structure-activity relationships of trimethoprim analogues binding to dihydrofolate reductase. AB - The machine learning program GOLEM from the field of inductive logic programming was applied to the drug design problem of modeling structure-activity relationships. The training data for the program were 44 trimethoprim analogues and their observed inhibition of Escherichia coli dihydrofolate reductase. A further 11 compounds were used as unseen test data. GOLEM obtained rules that were statistically more accurate on the training data and also better on the test data than a Hansch linear regression model. Importantly machine learning yields understandable rules that characterized the chemistry of favored inhibitors in terms of polarity, flexibility, and hydrogen-bonding character. These rules agree with the stereochemistry of the interaction observed crystallographically. PMID- 1454815 TI - Stable heparin-producing cell lines derived from the Furth murine mastocytoma. AB - Stable cell lines that synthesize heparin have been established from the Furth murine mastocytoma. The parental line (MST) divides in suspension every 14-18 h in growth medium supplemented with fetal bovine serum or defined growth factors. Adherent subclones were selected by adhesion to plastic culture vessels. Both adherent and nonadherent cells contain about 0.4 micrograms of glycosaminoglycan hexuronic acid per 10(6) cells, composed of 80% heparin and 20% chondroitin sulfate E. Deaminative cleavage of MST heparin by HNO2 at pH 1.5 released disaccharides that were similar in composition to those obtained from commercial heparin, except that disaccharides containing 3,6-O-desulfated GlcN units were not found. Greater than 90% of the glycosaminoglycans were stored in cytoplasmic granules, and challenge of the cells with dinitrophenylated bovine serum albumin and anti-dinitrophenyl IgE released a portion of the stored material. Growth studies of subclones showed that MST cells tolerate a 10-fold variation in glycosaminoglycan content. Incubation of cells with sodium chlorate reduced glycosaminoglycan sulfation by > 95% without affecting cell growth. Thus, granule glycosaminoglycans appear to be nonessential for growth of MST cells. PMID- 1454816 TI - Efficient transfer and sustained high expression of the human glucocerebrosidase gene in mice and their functional macrophages following transplantation of bone marrow transduced by a retroviral vector. AB - A recombinant retroviral vector (MFG-GC) was used to study the efficiency of transduction of the human gene encoding glucocerebrosidase (GC; D-glucosyl-N acylsphingosine glucohydrolase, EC 3.2.1.45), in mouse hematopoietic stem cells and expression in their progeny. Transfer of the GC gene to CFU-S (spleen cell colony-forming units) in primary and secondary recipients was virtually 100%. In mice 4-7 months after transplantation, highly efficient transfer of the human gene to bone marrow cells capable of long-term reconstitution was confirmed by detection of one or two copies per mouse genome in hematopoietic tissues and in cultures of pure macrophages. Expression of the human gene exceeded endogenous activity by several fold in primary and secondary CFU-S, tissues from long-term reconstituted mice, and explanted macrophages cultures. These studies are evidence of the feasibility of efficient transfer of the GC gene to hematopoietic stem cells and expression in their progeny for many months after reconstitution. The results of this study strengthen the rationale for gene therapy as a treatment for Gaucher disease. PMID- 1454817 TI - Human fusion proteins between interleukin 2 and IgM heavy chain are cytotoxic for cells expressing the interleukin 2 receptor. AB - We have constructed a hybrid cDNA coding for a fusion protein between human interleukin 2 and a truncated heavy chain from human immunoglobulin M. The protein encoded by this cDNA contains the entire interleukin 2 sequence including its signal peptide, fused at its C terminus to domains 2 to 4 of the immunoglobulin heavy-chain constant region. Cells transfected with the hybrid cDNA secrete multimeric forms of the fusion protein, which bind specifically to cells bearing high-affinity interleukin 2 receptors. This binding leads either to T-cell proliferation or, if complement is added, to T-cell death. Multimeric forms of the fusion protein with a molecular mass above 500 kDa mediate complement-dependent lysis but trigger proliferation inefficiently when compared with forms with a low molecular mass (< 500 kDa). In contrast, the latter efficiently mediate T-cell proliferation without inducing complement-dependent lysis. The high molecular mass fusion proteins could thus constitute valuable tools for specific immunosuppression in humans. PMID- 1454818 TI - Brain-derived neurotrophic factor augments rotational behavior and nigrostriatal dopamine turnover in vivo. AB - Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor (NGF)-related family of neutrophins, promotes the survival and differentiation of cultured nigral dopamine neurons. Two-week infusions of BDNF were made above the right pars compacta of the substantia nigra in adult rats. Systemic injection of these animals with (+)-amphetamine, a dopamine-releasing drug, induced 3 or 4 body rotations per minute directed away from the nigral infusion site. Neither supranigral NGF nor neocortical BDNF infusions induced rotational behavior. Systemic injections of the postsynaptic dopamine receptor agonist apomorphine did not induce rotations in these animals, demonstrating a presynaptic dopamine neuron locus for BDNF action. In support of this, neostriatal levels of the dopamine metabolite homovanillic acid (HVA) were elevated by 28%, and the HVA/dopamine and dihydroxyphenylacetic acid (DOPAC)/dopamine ratios were elevated by 56% and 34%, respectively, in the BDNF-infused brain hemisphere. BDNF augmented striatal concentrations of HVA and DOPAC and the metabolite/dopamine ratios to even greater extents after (+)-amphetamine injection, when peak rotational effects occurred. Intrastriatal infusions of BDNF produced fewer rotations per minute (1-2.5) after (+)-amphetamine and smaller elevations in HVA and the HVA/dopamine ratio (15% and 30%, respectively) than after supranigral delivery. Neither striatal dopamine, gamma-aminobutyric acid, nor acetylcholine high-affinity uptake or the synthetic enzymes for these neurotransmitters was altered by BDNF. These behavioral and neurochemical effects demonstrate an action of BDNF on dopamine neurons in vivo and are consistent with a potential role for BDNF in the treatment of Parkinson disease. PMID- 1454819 TI - Molecular characterization of NAD:arginine ADP-ribosyltransferase from rabbit skeletal muscle. AB - Mono-ADP-ribosylation is a reversible modification of proteins, with NAD:arginine ADP-ribosyltransferases (EC 2.4.2.31) and ADP-ribosylarginine hydrolases (EC 3.2.2.19) catalyzing the opposing reactions in an ADP-ribosylation cycle. A membrane-associated arginine-specific (mono)-ADP-ribosyltransferase was purified 215,000-fold from rabbit skeletal muscle. On the basis of the amino acid sequences of HPLC-purified tryptic peptides, degenerate oligonucleotide primers were synthesized and used in a polymerase chain reaction (PCR)-based procedure to generate cDNA. A specific probe, based on PCR-generated sequence, was used to screen a rabbit skeletal muscle cDNA library. A composite cDNA sequence, obtained from library screening and rapid amplification of the 5' end of the cDNA, contained a 981-base-pair open reading frame, encoding a 36,134-Da protein. The deduced amino acid sequence contained the sequences of the tryptic peptides, hydrophobic amino and carboxyl termini, and two potential sites for N-linked glycosylation. Escherichia coli cells transformed with an expression vector containing transferase-specific sequence expressed ADP-ribosyltransferase activity. A transferase-specific oligonucleotide probe recognized a 4-kilobase mRNA expressed primarily in rabbit skeletal and cardiac muscle. There was no extended similarity in deduced amino acid sequences of the muscle transferase and several bacterial ADP-ribosylating toxins. The hydrophobic amino and carboxyl termini may represent a signal peptide and a site for a glycosyl phosphatidylinositol anchor, respectively. PMID- 1454820 TI - Effect of Ca2+ on weak cross-bridge interaction with actin in the presence of adenosine 5'-[gamma-thio]triphosphate). AB - In the presence of the nucleotide analog adenosine 5'-[gamma-thio]triphosphate (ATP[gamma S]), effects of Ca2+ on stiffness and equatorial x-ray diffraction patterns of single skinned fibers of the rabbit psoas muscle were studied. It is shown that cross-bridges in the presence of ATP[gamma S] have properties of the weak-binding states of the ATP hydrolysis cycle. Raising the Ca2+ concentration up to pCa 4.5 has little effect on actin affinity of cross-bridges in the presence of ATP[gamma S]. However, the rate constants for cross-bridge dissociation and reassociation from and to actin are reduced by about 2 orders of magnitude. In addition, nucleotide affinity of the cross-bridge is much smaller at high Ca2+ concentrations. Implications for interpretation of fiber stiffness recorded during isotonic shortening and the rising phase of a tetanus are discussed. PMID- 1454821 TI - pH gradients across phospholipid membranes caused by fast flip-flop of un-ionized fatty acids. AB - A central, unresolved question in cell physiology is how fatty acids move across cell membranes and whether protein(s) are required to facilitate transbilayer movement. We have developed a method for monitoring movement of fatty acids across protein-free model membranes (phospholipid bilayers). Pyranin, a water soluble, pH-sensitive fluorescent molecule, was trapped inside well-sealed phosphatidylcholine vesicles (with or without cholesterol) in Hepes buffer (pH 7.4). Upon addition of a long-chain fatty acid (e.g., oleic acid) to the external buffer (also Hepes, pH 7.4), a decrease in fluorescence of pyranin was observed immediately (within 10 sec). This acidification of the internal volume was the result of the "flip" of un-ionized fatty acids to the inner leaflet, followed by a release of protons from approximately 50% of these fatty acid molecules (apparent pKa in the bilayer = 7.6). The proton gradient thus generated dissipated slowly because of slow cyclic proton transfer by fatty acids. Addition of bovine serum albumin to vesicles with fatty acids instantly removed the pH gradient, indicating complete removal of fatty acids, which requires rapid "flop" of fatty acids from the inner to the outer monolayer layer. Using a four-state kinetic diagram of fatty acids in membranes, we conclude that un-ionized fatty acid flip-flops rapidly (t1/2 < or = 2 sec) whereas ionized fatty acid flip-flops slowly (t1/2 of minutes). Since fatty acids move across phosphatidylcholine bilayers spontaneously and rapidly, complex mechanisms (e.g., transport proteins) may not be required for translocation of fatty acids in biological membranes. The proton movement accompanying fatty acid flip-flop is an important consideration for fatty acid metabolism in normal physiology and in disease states such as cardiac ischemia. PMID- 1454822 TI - Vibronic energy map and excited state vibrational characteristics of magnesium myoglobin determined by energy-selective fluorescence. AB - The vibrational frequencies of the singlet excited state of Mg-substituted myoglobin and relative absorption probabilities were determined by fluorescence line-narrowing spectroscopy. These spectra contain information on the structure of the excited state species, and the availability of vibrationally resolved spectra from excited state biomolecules should aid in elucidating their structure and reactivity. PMID- 1454823 TI - Differential effects of Bcl-2 on T and B cells in transgenic mice. AB - We have produced bcl-2 transgenic mice by using a construct which mimics the t(14;18) translocation in human follicular lymphomas. Although lymphoid tissues from all transgenic mice contained high levels of human Bcl-2 protein, transgene expression was differentially regulated within the B- and T-cell compartments of lines derived from various founder mice. We have characterized the phenotypes of two lines of bcl-2 transgenic mice (line 2 and line 6) in which bcl-2 transgene expression was restricted primarily to the T- or B-cell lineages, respectively. Analysis of line 6 lymphocytes revealed a polyclonal expansion of B cells, and these B cells exhibited prolonged survival in vitro. In line 2 mice, numbers of T cells in the peripheral lymphoid tissues were more moderately elevated despite enhanced T-cell survival in vitro. Line 2 transgenic mice also showed significantly increased proportions of thymocytes with a mature phenotype. Taken together, these findings suggest different roles for bcl-2 in the in vivo regulation of B- and T-cell development and homeostasis. PMID- 1454824 TI - Major histocompatibility complex class I-specific and -restricted killing of beta 2-microglobulin-deficient cells by CD8+ cytotoxic T lymphocytes. AB - Cytotoxic T lymphocytes (CTLs) recognize major histocompatibility complex (MHC) class I molecules, normally composed of a heavy chain, a beta 2-microglobulin (beta 2m), and peptide antigens. beta 2m is considered essential for the assembly and intracellular transport of MHC class I molecules as well as their peptide presentation to CTLs. Contrary to this dogma, we now report the generation of allospecific and restricted CD8+ and TCR alpha beta+ CTLs (where TCR is T-cell receptor) capable of killing beta 2m-deficient cells. Such CTLs were obtained by priming mice with live allogeneic beta 2m- spleen cells or mutant lymphoma cells producing MHC class I protein but no detectable beta 2m. Although both beta 2m- and beta 2m-expressing lymphoma cells were rejected in allogeneic mice, only the former were efficient inducers of CTLs recognizing beta 2m- cells. These CTLs were MHC class I (H-2Kb or Db)-specific and CD8-dependent and did not require serum as a source of external beta 2m in the culture. They could be induced across major and minor histocompatibility barriers. The H-2-restricted CTLs generated in the latter case failed to kill the antigen-processing-deficient target RMA-S cells. The results show that MHC class I heavy chains in beta 2m- cells can be transported to the cell surface and act as antigens or antigen presenting molecules to allospecific and MHC-restricted CTLs. PMID- 1454825 TI - Introduction of a retinoid reporter gene into the urodele limb blastema. AB - After amputation of the limb of an adult urodele amphibian at any point along the proximodistal axis, blastemal cells (the progenitor cells of the regenerate) give rise only to the missing structures. Retinoic acid (RA) is able to respecify the positional identity of the blastema to a more proximal value, thus raising the possibility that the RA response system is activated during limb regeneration. Cultured newt (Notophthalmus viridescens) limb cells were transfected by nuclear microinjection of plasmids which provided RA-sensitive reporter activity that could be normalized for differences in cell recovery and transfection efficiency. Such cells showed a dose-dependent response to RA in culture, and this required a functional RA response element. The cells were implanted under the wound epidermis of newt hindlimb blastemas. After injection of a proximalizing dose of RA there was a significant difference in the level of reporter activity dependent on a functional response element. When cells were implanted into contralateral proximal and distal hindlimb blastemas the proximal-to-distal ratio for activation of the reporter through the response element was approximately 3.5 fold, suggesting that a gene whose expression is regulated by RA could be differentially activated along the proximodistal axis during limb regeneration. PMID- 1454826 TI - Epidermal growth factor stimulates mouse placental lactogen I but inhibits mouse placental lactogen II secretion in vitro. AB - This study was undertaken to determine whether epidermal growth factor (EGF) regulates the secretion of mouse placental lactogen (mPL)-I and mPL-II. Primary cell cultures were prepared from placentas from days 7, 9, and 11 of pregnancy and cultured for up to 5 days. Addition of EGF (20 ng/ml) to the medium resulted in significant stimulation of mPL-I secretion by the second day of culture in cells from days 7 and 9 of pregnancy and significant inhibition of mPL-II secretion by the third or fourth day of culture in cells from days 7, 9, and 11. Dose-response studies carried out with cells from day 7 of pregnancy demonstrated that the minimum concentration of EGF that stimulated mPL-I secretion and inhibited mPL-II secretion was 1.0 ng/ml. EGF did not affect the DNA content of the cells or cell viability, assessed by trypan blue exclusion, nor did it have a general effect on protein synthesis. There are three types of PL-containing giant cells in mouse placental cell cultures: cells that contain either mPL-I or mPL-II and cells that contain both hormones. Immunocytochemical analysis and the reverse hemolytic plaque assay indicated that EGF treatment was accompanied by a significant increase in the number of cells that produce mPL-I, but among the PL cells that contained mPL-I, there was no change in the fraction of cells that contained only mPL-I or the fraction that contained both mPL-I and mPL-II. In contrast, EGF treatment did affect the distribution of mPL-II among PL cells. In control cultures, about 75% of the cells that contained mPL-II also contained mPL I, but in EGF-treated cultures, all of the cells that contained mPL-II also contained mPL-I. These data suggest that EGF regulates mPL-I and mPL-II secretion at least partly by regulating PL cell differentiation. PMID- 1454827 TI - Phage phi 29 regulatory protein p4 stabilizes the binding of the RNA polymerase to the late promoter in a process involving direct protein-protein contacts. AB - Transcription from the late promoter, PA3, of Bacillus subtilis phage phi 29 is activated by the viral regulatory protein p4. A kinetic analysis of the activation process has revealed that the role of protein p4 is to stabilize the binding of RNA polymerase to the promoter as a closed complex without significantly affecting further steps of the initiation process. Electrophoretic band-shift assays performed with a DNA fragment spanning only the protein p4 binding site showed that RNA polymerase could efficiently retard the complex formed by protein p4 bound to the DNA. Similarly, when a DNA fragment containing only the RNA polymerase-binding region of PA3 was used, p4 greatly stimulated the binding of RNA polymerase to the DNA. These results strongly suggest that p4 and RNA polymerase contact each other at the PA3 promoter. In the light of current knowledge of the p4 activation mechanism, we propose that direct contacts between the two proteins participate in the activation process. PMID- 1454828 TI - Intramolecular DNA triplexes: unusual sequence requirements and influence on DNA polymerization. AB - Homopurine-homopyrimidine mirror repeats are known to form intramolecular DNA triplexes in vitro. By probing with chemical agents specific for unusual DNA conformations, we have now demonstrated the formation of intramolecular triplexes consisting of G.G.C and T.A.T base triplets by DNA sequences that are neither homopurine-homopyrimidine nor mirror repeats. This finding significantly enlarges the number of sequences that could form DNA triplexes. The observed triplexes are stable under the conditions that are optimal for DNA polymerases in vitro. We found that triplex formation causes specific termination of DNA polymerization in vitro. This effect is detected for different DNA polymerases and may have implications for the regulation of DNA replication in vivo. PMID- 1454829 TI - Malignancy of eye melanomas originating in the retinal pigment epithelium of transgenic mice after genetic ablation of choroidal melanocytes. AB - Eye tumors of the retinal pigment epithelium (RPE) have been thought generally to be benign, whereas choroidal ones are malignant. To test this assumption in mice, the W/Wv (Kit) mutant genotype was introduced into melanoma-prone transgenic mice whose recombinant simian virus 40 transforming sequences are specifically expressed in pigment cells. W/Wv causes programmed death of neural crest-derived pigment cells, including choroidal ones, but leaves intact the brain-derived pigment cells, such as those in the RPE. Dysplastic cells arose in the RPE, contiguous with frank melanotic neoplasms. Invasion of the optic nerve, and tumor growth outside the orbit, attested to the malignancy of these RPE-derived melanomas. The widespread melanosis previously seen in mice with this transgene was absent when W/Wv was added, thus validating its chief origin from neural crest cells. PMID- 1454830 TI - A proposed function for spermine and spermidine: protection of replicating DNA against damage by singlet oxygen. AB - Like all aliphatic amines, the polyamines spermine and spermidine are physical quenchers of singlet molecular oxygen (1O2*). The rate constants of these processes were determined in vitro with photochemically generated 1O2* and the hydrocarbon rubrene as substrate, in pyridine. At millimolar concentration, spermine and spermidine should quench 1O2* in vivo and prevent it from damaging DNA. It is proposed that a biological function of polyamines is the protection of replicating DNA against oxidative damage. PMID- 1454831 TI - Spermine and spermidine protection of plasmid DNA against single-strand breaks induced by singlet oxygen. AB - Oxidative damage to DNA induced by singlet molecular oxygen (1O2*) includes single-strand breaks, which the biologically occurring 1O2* quenchers spermine and spermidine are shown to prevent. These polyamines at a physiological concentration (10 mM) reduce the percentage of the open circular form of pBR322 plasmid DNA, which is generated at the expense of the native supercoiled form when the plasmids are incubated with a chemical source of 1O2*, the water-soluble endoperoxide of 3,3'-(1,4-naphthylidene)dipropionate. Spermine and spermidine can be expected to protect DNA against other damaging effects of 1O2*. PMID- 1454832 TI - Reading-frame restoration with an apolipoprotein B gene frameshift mutation. AB - We examined a mutant human apolipoprotein B (apoB) allele that causes hypobetalipoproteinemia and has a single cytosine deletion in exon 26. This frameshift mutation was associated with the synthesis of a truncated apoB protein of the predicted size; however, studies in human subjects and minigene expression studies in cultured cells indicated that the mutant allele also yielded a full length apoB protein. The 1-base-pair deletion in the mutant apoB allele created a stretch of eight consecutive adenines. To understand the mechanism whereby the mutant apoB allele yielded a full-length apoB protein, the cDNA from cells transfected with the mutant apoB minigene expression vector was examined. Splicing of the mRNA was normal; however, 11% of the cDNA clones had an additional adenine within the stretch of eight adenines, yielding nine consecutive adenines. The insertion of the extra adenine, presumably during apoB gene transcription, is predicted to restore the correct apoB reading frame, thereby permitting the synthesis of a full-length apoB protein. PMID- 1454833 TI - Activin inhibits binding of transcription factor Pit-1 to the growth hormone promoter. AB - Activin A is a potent growth and differentiation factor related to transforming growth factor beta. In somatotrophs, activin suppresses the biosynthesis and secretion of growth hormone (GH) and cellular proliferation. We report here that, in MtTW15 somatotrophic tumor cells, activin decreased GH mRNA levels and inhibited expression of transfected GH promoter--chloramphenicol acetyltransferase fusion genes. Deletion mapping of nucleotide sequences mediating this inhibition led to the identification of a region that has previously been characterized as binding the pituitary-specific transcription factor Pit-1/GHF-1. Characterization of nuclear factor binding to this region demonstrated that binding of Pit-1 to the GH promoter is lost on activin treatment. These results indicate that activin-induced repression of GH biosynthesis is mediated by the loss of tissue-specific transcription factor binding to the GH promoter and suggest a possible general mechanism for other activin responses, whereby activin regulates the function of other POU- or homeodomain-containing transcription factors. PMID- 1454834 TI - Additional antitumor ecteinascidins from a Caribbean tunicate: crystal structures and activities in vivo. AB - Ecteinascidins (Ets), isolated from the Caribbean tunicate Ecteinascidia turbinata, protect mice in vivo against P388 lymphoma, B16 melanoma, M5076 ovarian sarcoma, Lewis lung carcinoma, and the LX-1 human lung and MX-1 human mammary carcinoma xenografts. Crystal structures of two tris(tetrahydroisoquinoline) Ets were investigated with single crystals of the 21 O-methyl-N12-formyl derivative of Et 729 and the natural N12-oxide of Et 743. Representatives of an additional class of Ets, Et 722 and Et 736, isolated from the same organism, were assigned tetrahydro-beta-carboline-substituted bis(tetrahydroisoquinoline) structures by NMR and fast atom bombardment MS spectra. PMID- 1454835 TI - Methodologic aspects of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine. AB - Tacrine is a cholinesterase inhibitor with activity in the central nervous system originally marketed for the reversal of competitive neuromuscular blockade. Because a marked reduction in cholinergic neurons is a hallmark of brain changes in Alzheimer disease, tacrine has been studied in two placebo-controlled clinical trials of patients with probable Alzheimer disease. Standard analysis of variance (ANOVA) and analysis of covariance (ANCOVA) have shown a difference between the tacrine group and the placebo group in terms of the cognitive component of the Alzheimer disease assessment scale at the end of the placebo-controlled phase. Due to limitations of ANOVA and ANCOVA, only a selected group of patients could be analyzed by those methods. A population pharmacodynamic model has been developed that allows the use of all observations from one or more trials to be combined. It can incorporate any sequence of active or placebo treatments and account for carryover effects of both placebo and active drug. The time courses of active or placebo treatment response and the development of tolerance to active drug or placebo can be defined. The model describes disease progression without treatment, the placebo effect, and the effect of tacrine as a function of daily dose. Placebo effect and active drug effects are modeled by effect site concentration components. PMID- 1454836 TI - Results and validation of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine. AB - Tacrine has been studied in two clinical trials of identical design in patients with probable Alzheimer disease. One trial enrolled patients in the United States, while the other enrolled patients in France. A population pharmacodynamic model has been used to describe the cognitive component of the Alzheimer disease assessment scale (ADASC) using mixed effects nonlinear regression. The model parameters and their population variability and covariance were estimated by using NONMEM. During an observation period of up to 5 months, the rate of disease progression was 6.17 ADASC units/year. The effect of tacrine was described best by a shift in the disease progress curve (-2.99 ADASC units or 177.6 days at a dose of 80 mg/day). The placebo effects associated with tacrine and placebo treatment were similar in magnitude and time course. There was no evidence of tolerance to tacrine but tolerance to the placebo treatment developed during the study. The size of the placebo effect in the French population was 76% larger than in the United States population, and the response to placebo diminished more slowly in the French population. PMID- 1454837 TI - Borna disease virus, a negative-strand RNA virus, transcribes in the nucleus of infected cells. AB - Borna disease virus, an unclassified infectious agent, causes immune-mediated neurologic disease in a wide variety of animal hosts and may be involved in pathogenesis of selected neuropsychiatric diseases in man. Initial reports suggested that Borna disease virus is a single-stranded RNA virus. We describe here a method for isolation of viral particles that has allowed definitive identification of the genome as containing a negative-polarity RNA. Further, we show that the viral mRNAs are transcribed in the nucleus. PMID- 1454838 TI - Brain proteins in plants: an Arabidopsis homolog to neurotransmitter pathway activators is part of a DNA binding complex. AB - The G box is a well-characterized cis-acting DNA regulatory element found in the promoters of several seemingly unrelated plant genes, including the alcohol dehydrogenase (Adh) gene of Arabidopsis thaliana. Using a monoclonal antibody screening approach coupled with electrophoretic mobility shift assays, we have isolated a cDNA clone encoding a protein that is part of the in vitro protein/G box complex. The derived amino acid sequence is homologous to a class of proteins in mammalian brains described as protein kinase C inhibitors and as activators of tyrosine and tryptophan hydroxylases, the rate-limiting enzymes in the pathways leading to the catecholamines and serotonin. The fact that a homologous member of this regulatory protein family is found in plants and is associated with binding to transcriptional regulatory elements suggests a much wider role for these proteins. PMID- 1454840 TI - Poly(L-alanine) as a universal reference material for understanding protein energies and structures. AB - We present a proposition, the "poly(L-alanine) hypothesis," which asserts that the native backbone geometry for any polypeptide or protein of M residues has a closely mimicking, mechanically stable, image in poly(L-alanine) of the same number of residues. Using a molecular mechanics force field to represent the relevant potential energy hypersurfaces, we have carried out calculations over a wide range of M values to show that poly(L-alanine) possesses the structural versatility necessary to satisfy the proposition. These include poly(L-alanine) representatives of minima corresponding to secondary and supersecondary structures, as well as poly(L-alanine) images for tertiary structures of the naturally occurring proteins bovine pancreatic trypsin inhibitor, crambin, ribonuclease A, and superoxide dismutase. The successful validation of the hypothesis presented in this paper indicates that poly(L-alanine) will serve as a good reference material in thermodynamic perturbation theory and calculations aimed at evaluating relative free energies for competing candidate tertiary structures in real polypeptides and proteins. PMID- 1454839 TI - Pur-1, a zinc-finger protein that binds to purine-rich sequences, transactivates an insulin promoter in heterologous cells. AB - Purine-rich stretches of nucleotides (GAGA boxes) are often found just upstream of transcription start sites in many genes, including insulin. Mutational analysis suggests that the GAGA box plays an important role in transcription of the rat insulin I gene. We identify here at least four different proteins that bind specifically to the insulin GAGA box. Using a GAGA oligonucleotide, we have isolated a cDNA encoding a sequence-specific protein from a HIT (hamster insulinoma cell line) lambda gt11 library. This protein, which we designate Pur-1 (for purine binding), binds to the GAGA boxes of the rat insulin I and II genes and the human islet amyloid polypeptide gene. Pur-1 is a potent transactivator in both pancreatic and nonpancreatic cells. Furthermore, Pur-1 is able to activate an intact insulin promoter in HeLa cells, where it is normally inactive. PMID- 1454841 TI - Tumor necrosis factor alpha response elements in the HLA-DRA promoter: identification of a tumor necrosis factor alpha-induced DNA-protein complex in astrocytes. AB - The cytokine tumor necrosis factor alpha (TNF-alpha) alone does not induce class II major histocompatibility complex (MHC) expression in most primary cells but can regulate ongoing class II expression in either a positive or negative fashion. The mechanism(s) by which TNF-alpha enhances interferon gamma (IFN gamma)-induced class II expression was examined in a primary cell type, the astrocyte, by transient transfection of the HLA-DRA promoter linked to a chloramphenicol acetyltransferase reporter gene (DRA-CAT). We show that TNF alpha, while having no effect on its own, can synergize with IFN-gamma to increase the level of promoter activity of a DRA-CAT construct. Three known sequences--W, X, and Y--are required for TNF-alpha enhancement of IFN-gamma induced promoter activity. The corollary effect of TNF-alpha on DNA-binding proteins specific for these elements was examined. A previous report described a DNA-binding protein, IFN-gamma-enhanced factor X (IFNEX), which is upregulated by IFN-gamma in astrocytes and is specific for the X box of the DRA promoter. In this study, we found that TNF-alpha alone did not induce any nuclear proteins; however, combined treatment of astrocytes with both IFN-gamma and TNF-alpha induced a DNA-protein complex of slower electrophoretic mobility than IFNEX. The TNF-alpha-induced complex (TIC-X) has specificity for the X element of the DRA promoter. These results suggest a mechanism by which TNF-alpha enhances IFN-gamma induced class II MHC expression via the formation of TIC-X. PMID- 1454842 TI - DNA rearrangement causes hepatocarcinogenesis in albumin-plasminogen activator transgenic mice. AB - Hepatocyte-directed production of urokinase-type plasminogen activator (uPA) in transgenic mice is hepatotoxic. Infrequently, hepatocytes arise that do not express uPA, due to physical loss of transgene DNA, and these cells clonally repopulate the entire liver within 3 months of birth. Surprisingly, hepatic tumors appear in these mice beginning at 8 months of age despite the fact that uPA is not oncogenic or genotoxic. Analysis of the transgene locus reveals that tumors arise only from a particular subclass of transgene-deficient cells in which the entire transgene array, and possibly a significant amount of flanking DNA, is deleted. Considering that all transgene-deficient regenerative nodules undergo extensive replication but only a subset gives rise to tumors, we propose that loss of genomic DNA, not mitogenesis per se, is a primary carcinogenic determinant in this model of hepatocarcinogenesis. PMID- 1454843 TI - Stable heteroplasmy for a large-scale deletion in the coding region of Drosophila subobscura mitochondrial DNA. AB - Due to the extremely economic organization of the animal mitochondrial genome, large-scale deletions are rarely found in animal mtDNA. We report the occurrence of a massive deletion in the coding region of mtDNA in Drosophila subobscura. Restriction mapping and nucleotide sequence analysis revealed that the deletion encompasses six protein genes and four tRNAs. All individuals of an isofemale strain proved to be heteroplasmic for normal and deficient mtDNA molecules. This type of heteroplasmy resembles one observed in patients with mitochondrial myopathies but differs in that the fitness of heteroplasmic flies is not significantly reduced even though the mutant mtDNA constitutes 50-80% of total mtDNA in most of the individuals studied. The heteroplasmic strain is genetically stable: despite extensive screening not a single homoplasmic fly was observed since the foundation of the line. PMID- 1454844 TI - The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. AB - Biosphere 2 is a 3.15-acre space containing an ecosystem that is energetically open (sunlight, electric power, and heat) but materially closed, with air, water, and organic material being recycled. Since September 1991, eight subjects (four women and four men) have been sealed inside, living on food crops grown within. Their diet, low in calories (average, 1780 kcal/day; 1 kcal = 4.184 kJ), low in fat (10% of calories), and nutrient-dense, conforms to that which in numerous animal experiments has promoted health, retarded aging, and extended maximum life span. We report here medical data on the eight subjects, comparing preclosure data with data through 6 months of closure. Significant changes included: (i) weight, 74 to 62 kg (men) and 61 to 54 kg (women); (ii) mean systolic/diastolic blood pressure (eight subjects), 109/74 to 89/58 mmHg (1 mmHg = 133 Pa); (iii) total serum cholesterol, from 191 +/- 11 to 123 +/- 9 mg/dl (mean +/- SD; 36% mean reduction), and high density lipoprotein, from 62 +/- 8 to 38 +/- 5 (risk ratio unchanged); (iv) triglyceride, 139 to 96 mg/dl (men) and 78 to 114 mg/dl (women); (v) fasting glucose, 92 to 74 mg/dl; (vi) leukocyte count, 6.7 to 4.7 x 10(9) cells per liter. We conclude that drastic reductions in cholesterol and blood pressure may be instituted in normal individuals in Western countries by application of a carefully chosen diet and that a low-calorie nutrient-dense regime shows physiologic features in humans similar to those in other animal species. PMID- 1454845 TI - Activation of estrogen receptor transfected into a receptor-negative breast cancer cell line decreases the metastatic and invasive potential of the cells. AB - Breast cancers containing estrogen receptors are responsive to antiestrogen treatment and have a better prognosis than estrogen receptor-negative tumors. The loss of estrogen and progesterone receptors appears to be associated with a progression to less-differentiated tumors. We transfected the human estrogen receptor into the estrogen receptor-negative metastatic breast cancer cell line MDA-MB-231 in an attempt to restore their sensitivity to antiestrogens. Two stable sublines of MDA-MB-231 cells (HC1 and HE5) expressing functional estrogen receptors were studied for their ability to grow and invade in vitro and to metastasize in athymic nude mice. The number and size of lung metastases developed by these two sublines in ovariectomized nude mice was not markedly altered by tamoxifen but was inhibited 3-fold by estradiol. Estradiol also significantly inhibited in vitro cell proliferation of these sublines and their invasiveness in Matrigel, a reconstituted basement membrane, whereas the antiestrogens 4-hydroxytamoxifen and ICI 164,384 reversed these effects. These results show that estradiol inhibits the metastatic ability of estrogen receptor negative breast cancer cells following transfection with the estrogen receptor, whereas estrogen receptor-positive breast cancers are stimulated by estrogen, indicating that factors other than the estrogen receptor are involved in progression toward hormone independence. Reactivation or transfer of the estrogen receptor gene can therefore be considered as therapeutic approaches to hormone independent cancers. PMID- 1454846 TI - Morphological changes in liposomes caused by polymerization of encapsulated actin and spontaneous formation of actin bundles. AB - Spherical giant liposomes that had encapsulated skeletal-muscle G-actin were made by swelling a dried lipid mixture of dimyristoyl phosphatidylcholine/cardiolipin, 1:1 (wt/wt), in a solution of G-actin/CaCl2 at 0 degree C. Polymerization of the encapsulated G-actin into actin filaments was achieved by raising the temperature to 30 degrees C. We observed the subsequent shape changes of the liposomes by dark-field and differential interference-contrast light microscopy. After approximately 40 min, which was required for completion of actin polymerization, two shapes of liposome were evident: dumbbell and disk. Elongation of the dumbbell-shaped liposomes was concomitant with actin polymerization. Polarization microscopy showed that actin filaments formed thick bundles in the liposomes and that these filaments lay contiguous to the periphery of the liposome. Localization of actin filaments in the liposomes was confirmed by observation of rhodamine phalloidin-conjugated actin filaments by fluorescence microscopy. Both dumbbell- and disk-shaped liposomes were rigid and kept their shapes as far as actin filaments were stabilized. In contrast, liposomes containing bovine serum albumin were fragile, and their shapes continually fluctuated from Brownian motion, indicating that the actin bundles served as mechanical support for the liposome shapes. PMID- 1454847 TI - Similarity between fluorescein-specific T-cell receptor and antibody in chemical details of antigen recognition. AB - A computer-generated model of the single-chain variable V alpha V beta fragment of the RFL3.8 T-cell receptor (TCR) specific for fluorescein served as a starting point for mutagenesis aimed at identification of its antigen-contacting residues. Selected backbone segments of the model representing regions of prominent sequence similarity between antibodies and TCRs were least-squares superimposed onto the corresponding segments of the crystallographically resolved 4-4-20 antibody complexed with its antigen, fluorescein. The superimposition placed the antibody-bound fluorescein molecule close to a cavity on the surface of the TCR model formed by the complementarity-determining region (CDR) loops. Some of the TCR cavity forming loops displayed sequence motifs related to canonical CDR loops previously found in antibodies. Six putative amino acid contacts were identified and single-chain TCRs with mutations at each of these positions were expressed in Escherichia coli, purified, refolded, and assayed for fluorescein binding. Five of the six mutations resulted in a loss of detectable binding. These RFL3.8 antigen combining site residues are distributed among the beta 3, alpha 1, and alpha 2 CDR loops and show striking chemical similarity to the known fluorescein contact residues on 4-4-20. Thus, antibodies and TCRs are similar both in their overall architecture and in the chemical details of specific antigen recognition. PMID- 1454848 TI - Phosphorylation state and DNA-binding activity of c-Jun depend on the intracellular concentration of binding sites. AB - The DNA-binding activity of c-Jun expressed in eukaryotic cells was found to be markedly enhanced if the intracellular concentration of binding sites for this transcription factor was increased by cotransfection of specific plasmid DNA. Dephosphorylation experiments, phosphate mapping studies, and mutational analysis indicate that phosphorylation of a cluster of serine and threonine residues situated in close proximity to the DNA-binding domain is responsible for the observed adaptation of c-Jun activity to the intracellular concentration of accessible target sites. PMID- 1454849 TI - Glutathione deficiency increases hepatic ascorbic acid synthesis in adult mice. AB - Glutathione deficiency, induced in adult mice by administering buthionine sulfoximine (an inhibitor of glutathione synthesis), led to a rapid and substantial increase in ascorbate in the liver. This effect was apparent 2-4 hr after giving the inhibitor; subsequently, the level of ascorbate decreased and that of dehydroascorbate increased markedly, supporting the conclusion that glutathione functions physiologically to keep ascorbate in its reduced form. In kidney and lung also, ascorbate levels decreased, and dehydroascorbate increased. Increased synthesis of ascorbate in glutathione-deficient adult mice seems to protect against tissue damage. In contrast, newborn rats, which (like guinea pigs and humans) apparently do not synthesize ascorbate, suffer severe damage to liver and other organs; previous studies showed that administration of ascorbate prevents such tissue damage. The findings support the view that the antioxidant actions of glutathione and ascorbate are closely linked and involve a mechanism in which decrease of the glutathione level, perhaps associated with an oxidative event, stimulates ascorbate synthesis. PMID- 1454850 TI - Calcium-myristoyl protein switch. AB - Recoverin, a recently discovered member of the EF-hand superfamily of Ca(2+) binding proteins, serves as a Ca2+ sensor in vision. The amino terminus of the protein from retinal rod cells contains a covalently attached myristoyl or related N-acyl group. We report here studies of unmyristoylated and myristoylated recombinant recoverin designed to delineate the biological role of this hydrophobic unit. Ca2+ induces the binding of both the unmyristoylated and myristoylated proteins to phenyl-agarose, a hydrophobic support. Binding was half maximal at 1.1 and 1.0 microM Ca2+, respectively. The Hill coefficients of 1.8 and 1.7, respectively, indicate that binding was cooperative. In contrast, Ca2+ induced the binding of myristoylated but not of unmyristoylated recoverin to rod outer segment membranes. Binding to these membranes was half-maximal at 2.1 microM Ca2+, and the Hill coefficient was 2.4. Likewise, myristoylated but not unmyristoylated recoverin exhibited Ca(2+)-induced binding to phosphatidylcholine vesicles. These findings suggest that the binding of Ca2+ to recoverin has two effects: (i) hydrophobic surfaces are exposed, allowing the protein to interact with complementary nonpolar sites, such as the aromatic rings of phenyl-agarose; and (ii) the myristoyl group is extruded, enabling recoverin to insert into a lipid bilayer membrane. The myristoyl group is likely to be an active participant in Ca2+ signaling by recoverin and related EF-hand proteins such as visinin and neurocalcin. PMID- 1454851 TI - Characterization by yeast artificial chromosome cloning of the linked apolipoprotein(a) and plasminogen genes and identification of the apolipoprotein(a) 5' flanking region. AB - The apoprotein(a) [apo(a)] gene encodes a protein component of the circulating lipoprotein(a) [Lp(a)]. The apo(a) gene is highly homologous to the plasminogen gene. It encodes one of the most polymorphic human proteins, due to variability in the number of repetitions of structures called kringles. In addition, Lp(a) levels vary among individuals by more than two orders of magnitude, the high levels being highly correlated with predisposition to early atherosclerotic disease. To better understand the genetics and function of the apo(a) gene, we have cloned in yeast artificial chromosome vectors DNA fragments comprising the linked apo(a) and plasminogen genes and other members of the plasminogen family. By a combination of pulsed-field gel electrophoresis and genome walking experiments, we have identified the 5' portion and flanking regions of the apo(a) gene. PMID- 1454852 TI - Dominant genetics using a yeast genomic library under the control of a strong inducible promoter. AB - In Saccharomyces cerevisiae, numerous genes have been identified by selection from high-copy-number libraries based on "multicopy suppression" or other phenotypic consequences of overexpression. Although fruitful, this approach suffers from two major drawbacks. First, high copy number alone may not permit high-level expression of tightly regulated genes. Conversely, other genes expressed in proportion to dosage cannot be identified if their products are toxic at elevated levels. This work reports construction of a genomic DNA expression library for S. cerevisiae that circumvents both limitations by fusing randomly sheared genomic DNA to the strong, inducible yeast GAL1 promoter, which can be regulated by carbon source. The library obtained contains 5 x 10(7) independent recombinants, representing a breakpoint at every base in the yeast genome. This library was used to examine aberrant gene expression in S. cerevisiae. A screen for dominant activators of yeast mating response identified eight genes that activate the pathway in the absence of exogenous mating pheromone, including one previously unidentified gene. One activator was a truncated STE11 gene lacking approximately 1000 base pairs of amino-terminal coding sequence. In two different clones, the same GAL1 promoter-proximal ATG is in-frame with the coding sequence of STE11, suggesting that internal initiation of translation there results in production of a biologically active, truncated STE11 protein. Thus this library allows isolation based on dominant phenotypes of genes that might have been difficult or impossible to isolate from high-copy number libraries. PMID- 1454853 TI - Purification of human leukotriene C4 synthase. AB - Leukotriene (LT) C4 synthase, the enzyme that catalyzes the conjugation of LTA4 with reduced glutathione to form LTC4, was purified to homogeneity from the KG-1 myeloid cell line after solubilization of the microsomes utilizing a combination of 0.4% sodium deoxycholate and 0.4% Triton X-102. The solubilized enzyme was then applied to an S-hexyl-glutathione-agarose column that was eluted by the use of 7.5 mM probenecid. After removal of the probenecid by sequential concentration and dilution in an Amicon concentrator, the enzyme was additionally purified and concentrated by binding to and elution from approximately 75 mg of S-hexyl glutathione-agarose. The enzyme was further resolved by electrophoresis with a nondenaturing Tris-glycine gel, and the LTC4 synthase activity was localized to slices 3 and 4. When the remainder of the eluate from the nondenaturing gel was precipitated by acetone and analyzed by 14% SDS/PAGE with silver staining, a single protein band of 18 kDa was associated with LTC4 synthase activity and was not present in the eluates of slices lacking activity. The overall recovery was 12.5%. In a separate preliminary purification, in which the yield was only approximately 1%, the eluates of the nondenaturing gel had also revealed a single protein of 18 kDa by SDS/PAGE, which was present only in the eluates with LTC4 synthase activity. These data identify LTC4 synthase as a protein of 18 kDa, a size consistent with its membership in the microsomal glutathione S-transferase family. PMID- 1454854 TI - Transcription-dependent and transcription-independent nucleosome disruption induced by dioxin. AB - In mouse hepatoma cells, both the regulatory and the transcribed regions of the cyp1a1 gene assume a nucleosomal configuration when the gene is silent; two nucleosomes occupy specific sites at the transcriptional promoter. Activation of transcription by 2,3,7,8-tetrachlorodibenzo-p-dioxin is accompanied by changes in chromatin structure, which depend upon a functional aromatic hydrocarbon (Ah) receptor. In the transcribed region of the gene, nucleosome disruption occurs as a consequence of RNA elongation. In contrast, at the promoter, loss of positioned nucleosome sis independent of transcription and represents an event in the mechanism by which the liganded Ah receptor enhances transcriptional initiation. PMID- 1454855 TI - Characterization of the tumor suppressor protein p53 as a protein kinase C substrate and a S100b-binding protein. AB - We report here that the negative cell cycle regulator protein p53 is an in vivo and in vitro substrate for protein kinase C, a cellular receptor for the tumor promoter phorbol esters. We also demonstrate that p53 interacts in a calcium dependent manner with S100b, a member of the S100 protein family involved in cell cycle progression and cell differentiation, and that such an interaction inhibits in vitro p53 phosphorylation by protein kinase C. The interaction between p53 and S100b was utilized for the purification of cellular and recombinant murine p53 by affinity chromatography with S100b-Sepharose. Furthermore, and of particular interest, we have shown that purified p53 undergoes temperature-dependent oligomerization and that the interaction between S100b and p53 not only induces total inhibition of p53 oligomerization but also promotes disassembly of the p53 oligomers. We suggest that these effects result from the binding of S100b to the multifunctional basic C-terminal domain of p53 and propose that p53 may be a cellular target for the S100 protein family members involved in the control of the cell cycle at the G0-G1/S boundary. PMID- 1454856 TI - Subpicosecond equilibration of excitation energy in isolated photosystem II reaction centers. AB - Photosystem II reaction centers have been studied by femtosecond transient absorption spectroscopy. We demonstrate that it is possible to achieve good photoselectivity between the primary electron donor P680 and the majority of the accessory chlorins. Energy transfer can be observed in both directions between P680 and these accessory chlorins depending on which is initially excited. After excitation of either P680 or the other chlorins, the excitation energy is observed to equilibrate between the majority of these pigments at a rate of 100 +/- 50 fs-1. This energy-transfer equilibration takes place before any electron transfer reactions and must therefore be taken into account in studies of primary electron-transfer reactions in photosystem II. We also show further evidence that the initially excited P680 excited singlet state is delocalized over at least two chlorins and that this delocalization lasts for at least 200 fs. PMID- 1454857 TI - Detection of dystrophin in the postsynaptic density of rat brain and deficiency in a mouse model of Duchenne muscular dystrophy. AB - Duchenne muscular dystrophy (DMD) is a common, lethal, chromosome X-linked inherited disease. Moderate cognitive impairment is a feature of DMD, but the underlying mechanisms are unknown. DMD is characterized by a defect in a protein, dystrophin, that is located predominantly in muscle but has been detected in brain. We sought to directly localize dystrophin within the complex synaptic structure of the cerebral cortex by focusing on the postsynaptic density (PSD), which appears to be central to synaptic function. We report that a specific anti dystrophin antibody (anti 6-10) recognizes three distinct proteins in the purified PSD: the 400-kDa dystrophin and two previously unidentified dystrophin related proteins of 120 and 110 kDa. These proteins exhibited differential regional expression in PSDs from cerebral cortex, cerebellum, and olfactory bulb. In the cortical PSD, the 400-kDa dystrophin was predominant, whereas the 120-kDa protein was the major species in cerebellum and olfactory bulb PSDs. The three proteins were differentially expressed in the PSD during cortical development: the 400-kDa protein exhibited a selective 9-fold increase during postnatal days 7 to 10, suggesting a normal physiological role in synaptic maturation. The PSD from the mdx mouse, a model of human DMD, contained no detectable 400-kDa dystrophin but expressed the two dystrophin-related proteins. Our results indicate that brain dystrophins are localized to the PSD, potentially as three isoforms, and raise the possibility that cognitive abnormalities in DMD are attributable to synaptic dysfunction associated with deficits in brain dystrophin molecules. PMID- 1454858 TI - Manual therapy: a special issue and a special topic. PMID- 1454859 TI - Special issue: Manual therapy. PMID- 1454860 TI - Manual therapy: a critical assessment of role in the profession of physical therapy. AB - Interest in manual therapy appears to continue to grow among physical therapy clinicians and educators throughout the world even though the underlying concepts and techniques have not been justified by a knowledge base. The purposes of this article are to critically assess the role of manual therapy within the physical therapy profession and to provide an introduction to the other articles in this special issue. Eisner's model of explicit, implicit, and null curricula is used as a framework for our analysis and our discussion of manual therapy. The explicit area of manual therapy includes discussions of the definition and the role of manual therapy, the scientific rationale for manual therapy, and manual therapy in education and a comparison of manual therapy evaluative frameworks. The implicit area deals with the role of clinical decision making and critical thinking in manual therapy in education and rehabilitation. In the null (unaddressed) area of manual therapy, we suggest directions for future development and research. PMID- 1454861 TI - Efficacy of manual therapy. AB - The use of manual therapy to treat somatic pain syndromes and associated disabilities is widespread. Yet, the efficacy of manual therapy has not been previously established because equivocal findings in the literature prevent definitive conclusions. The purposes of this article are (1) to establish objective criteria for judging the validity of manual therapy research, (2) to identify and discuss the results of those trials that were determined to be valid demonstrations of treatment efficacy or valid demonstrations of nonuseful therapy, and (3) to determine whether patients who benefit from manual therapy have common characteristics. The abstracts or full reports of 146 titles with appropriate key words were reviewed. Of these, 105 studies were not primary studies of manual therapy and were thus eliminated from review. In the 41 remaining studies, 18 did not utilize statistical comparisons or report blinded assessment of outcome measures. Nine controlled studies yielded negative results, but the statistical power or minimum sample size required to detect potential differences between manual therapy and control groups was not described. The 14 studies that met the efficacy criteria were categorized by the following factors: (1) the anatomical region of intervention, (2) pragmatic versus explanatory goals, and (3) primary intervention (manipulation, mobilization, combination). There was a paucity of valid explanatory research in all areas and a particular absence of controlled trials involving manual therapy applied to the peripheral joints. Manual therapy for low back pain, however, was studied extensively. The analysis of valid trials provided clear evidence that manual therapy, particularly manipulation, can be an effective modality when used to treat patients who have low back pain. A preliminary "profile" of the patient with low back pain who would likely benefit from manual therapy included acute symptom onset with less than a 1-month duration of symptoms, central or paravertebral pain distribution, no previous exposure to spinal manipulation, and no pending litigation or workers' compensation. Suggestions for future manual therapy research are discussed. PMID- 1454862 TI - Measurement of accessory motion: critical issues and related concepts. AB - The term "manual therapy" has traditionally been associated with physical therapists who examine and treat patients who have disorders related to the musculoskeletal system. In addition to using instruments to collect patient data, these therapists use a large variety of manually applied examination procedures. Range-of-motion tests, manual muscle tests, neurological tests, and palpation tests are just a few of the categories of tests these therapists use as part of the clinical decision-making process. The major sources of error that can affect the usefulness of manually obtained measurements are discussed. The literature that provides the theoretical and clinical bases for the assessment of joint surface movement is thoroughly reviewed. Conclusions are made about what is currently known about the usefulness of accessory motion tests. Suggestions are made for future research needs in order to clarify and enhance the usefulness of accessory motion tests and other examination procedures used by manual therapists. PMID- 1454863 TI - Clinical reasoning in manual therapy. AB - Clinical reasoning refers to the cognitive process or thinking used in the evaluation and management of a patient. In this article, clinical reasoning research and expert-novice studies are examined to provide insight into the growing understanding of clinical reasoning and the nature of expertise. Although hypothetico-deductive methods of reasoning are used by clinicians at all levels of experience, experts appear to possess a superior organization of knowledge. Experts often reach a diagnosis based on pure pattern recognition of clinical patterns. With an atypical problem, however, the expert, like the novice, appears to rely more on hypothetico-deductive clinical reasoning. Five categories of hypotheses are proposed for physical therapists using a hypothetico-deductive method of clinical reasoning. A model of the clinical reasoning process for physical therapists is presented to bring attention to the hypothesis generation, testing, and modification that I feel should take place through all aspects of the patient encounter. Examples of common errors in clinical reasoning are highlighted, and suggestions for facilitating clinical reasoning in our students are made. PMID- 1454864 TI - A rationale for the treatment of back pain and joint pain by manual therapy. AB - Manual therapy, with its emphasis on joint movement and exercise, has become increasingly important for the treatment of pain and dysfunction of the musculoskeletal system. The rationale used to explain the success of manual therapy has changed radically in recent years. Early explanations, which included concepts such as adjusting joint subluxations, restoring bony alignment, and reducing nuclear protrusion, have been shown to have no basis in fact. Current biological research shows the value of movement in maintaining the health and strength of collagenous, muscular, and bony tissues and emphasizes the need for joint movement and for relatively high levels of activity throughout the life cycle. The musculoskeletal system thrives on stress and movement and reacts adversely to prolonged rest or immobilization. The problems associated with working or recreational postures involving prolonged loading at or near the limit of joint range of motion are considered together with a rationale for appropriate therapeutic management. Explanations are provided to enable an understanding of the success of intensive physical therapy for chronic back pain and for manipulation in the treatment of the acute painful locked back. PMID- 1454865 TI - The effects of manual therapy on connective tissue. AB - The purpose of this manuscript is to examine the known and theoretical mechanical effects of therapeutic manual techniques on the connective tissue (CT) of joints and fasciae. Typical CT structures that could be influenced by manual techniques will be discussed. The behavior of CT under loading and the influence of immobilization on CT will be examined. The forces developed during manual techniques will be described, and their potential effects on the physical properties of CT will be discussed. Research priorities regarding the effects of manual therapy on CT will be outlined. PMID- 1454866 TI - The sacroiliac joint: a critical review. AB - Clinicians continue to focus attention on the sacroiliac joint (SIJ) as one cause of low back pain. Considerable literature now exists to support the contention that symptoms arise from the sacroiliac region. In the last couple of decades, studies with quantitative data, often using sophisticated methods, have added to our knowledge from earlier descriptive reports of SIJ morphology and motion. The unique morphology of the SIJ, together with its location, makes study of the SIJ complex. All reported studies have limitations such as small sample size or lack of randomization or methodology. The purpose of this article is to review the literature to determine the support for current beliefs, opinions, and theories on joint morphology, life-span changes, and motion. Clinicians should provide well-documented clinical case-study series if we are to understand what occurs with treatments designed to affect the SIJ. PMID- 1454867 TI - The treatment of the sacroiliac joint component to low back pain: a case report. AB - This case report describes the treatment of a patient who had symptoms and signs suggestive of a sacroiliac joint component of low back pain. The patient developed right-sided low back pain without provocation. He appeared to have sacroiliac joint dysfunction, excessive right hip lateral rotation, and limited right hip medial rotation. The patient's habit of crossing his right leg over his left leg while sitting was believed to have contributed to the excessive lateral hip rotation. After treating the sacroiliac joint and restoring symmetrical hip rotation, the patient no longer complained of low back pain. This case report suggests that asymmetrical hip rotation may contribute to what is often called a sacroiliac joint component of low back pain. PMID- 1454868 TI - The use of an eclectic approach for the treatment of low back pain: a case study. AB - The purposes of this case report are (1) to describe an examination approach that relates identification of an impairment to a disability and (2) to describe an eclectic treatment approach for an individual with low back pain (LBP). The individual described in this case report is an intercollegiate athlete who, because of chronic LBP, was unable to perform his sport of pole vaulting. The findings of the physical therapy examination suggested that an impairment of lumbar motion prevented the patient from assuming the spinal position necessary for pole vaulting. The goals of the treatment consisted of increasing the patient's lumbar motion to that required for pole vaulting and to have the patient pole vault without pain or stiffness. The treatment approach that was used combined procedures described by Maitland, McKenzie, and others. The rationale for the use of these procedures and their limitations are discussed. PMID- 1454869 TI - Treatment of limited shoulder motion: a case study based on biomechanical considerations. AB - This article describes the management of a 57-year-old female patient following a fracture and dislocation of the right humeral head. The treatment of the patient involved the use of thermal agents, manual therapy, continuous passive motion, and splinting of the arm in an elevated position. We describe an approach to treatment of limited shoulder motion that is focused on identifying and applying tension to restricting structures rather than restoration of translatory gliding movements of the humeral head. Our treatment approach is based on recent data from biomechanical studies that challenge the concave-convex theory of arthrokinematic motion first described by MacConaill. We believe that tension in capsular tissues, rather than joint surface geometry, may control the translatory movements of the humeral head. The rationale for treatment involving low-load prolonged stress to tissues in the form of continuous passive motion and splinting is discussed as well as potential limitations of more brief forms of stress such as joint mobilization and manual stretching. PMID- 1454870 TI - Diversity needed. PMID- 1454871 TI - Application of time-resolved diffuse reflectance techniques in studies of reaction intermediates in suspensions of Bacillus subtilis. AB - Short lived reaction intermediates such as triplet states and free radicals can be detected in vivo using laser photolysis techniques with time-resolved diffuse reflectance detection. This novel approach is illustrated for bacterial suspensions of Bacillus subtilis. PMID- 1454872 TI - Inactivation of lambda phage with 658 nm light using a DNA binding porphyrin sensitizer. AB - Exposure of lambda phage to 658 nm light in the presence of 5,10,15,20-tetrakis (1-methyl-4-pyridyl)-21H,23H-porphine, tetra-p-tosylate leads to complete (greater than 7 logs) inactivation as measured by the plaque assay. The sensitizer without light and 658 nm photolysis of lambda phage in the absence of sensitizer do not lead to a measurable decrease in viral inactivity. Viral inactivation is not dependent upon the presence of oxygen. PMID- 1454873 TI - Reversible photocycloaddition of a 4',5'-dihydropsoralen derivative with thymine. AB - The photocycloaddition reaction between a 4',5'-dihydropsoralen derivative and thymine was studied in solution using a synthetic bichromophoric model 8 in which the two rings are associated by a tetramethylene chain. In water this model molecule exhibits intramolecular ring-ring stacking interactions as evidenced by UV and NMR spectroscopies. Irradiation at 365 nm at usual concentrations (greater than or equal to 5.10(-4) M) leads exclusively to a regio- and stereo-selective dimerization reaction involving the 3,4 double bonds of the psoralen moities. Extreme dilutions (ca less than or equal to 2.10(-5) M) were necessary to observe the intramolecular reaction which results in the exclusive formation of a 3,4 cis anti adduct. This reaction is completely reversed by irradiation at 254 nm. These results are discussed with regard to the behavior of the homologous models in which the furan part of the psoralen ring is not hydrogenated. These latter compounds also lead exclusively to a 3,4 cis-anti adduct. It appears that saturation of the furan ring increases strongly the quantum yield of the photoaddition at 365 nm (0.01----0.18) and that the triplet excited state of the 4',5'-dihydropsoralen is involved in the photoaddition. PMID- 1454874 TI - Oxidation of phosphatidylcholine membranes by singlet oxygen generated in the gas phase. AB - Singlet-oxygen (1O2) was generated in the gas phase by heterogeneous photosensitization and bubbled into suspensions of phosphatidylcholine (PC) liposomes. Lipid peroxidation and membrane lysis were observed, and were dependent on the 1O2 concentration and the degree of unsaturation of the liposome. An analysis based on large target diffusion theory indicates that approximately 5000, 2800, and 1600 interactions were required for the lysis of large dioleoylPC, dilinoleoylPC and dilinolenoylPC liposomes, respectively. PMID- 1454875 TI - Properties of cremophor EL micelles probed by fluorescence. AB - Using 1-anilino,8-naphthalenesulfonic acid (ANS) as a probe, we examined properties of micelles of Cremophor EL, an amphipathic agent which can solubilize hydrophobic photosensitizing agents and promote their distribution to plasma lipoprotein. In aqueous solution, Cremophor micelles persisted for several hours after dilution below the critical micellar concentration (CMC). After equilibrium was reached, we found a CMC of 0.009% (wt/vol). Fluorescence data suggest that the micellar environment of ANS binding has a dielectric constant of approximately 27. Cremophor also reverses examples of multi-drug resistance associated with impaired accumulation of anti-tumor agents, e.g. daunorubicin. Although the latter drug is relatively hydrophilic, fluorescence spectroscopy and anisotropy studies indicate an association with Cremophor. Moreover, resistance reversal occurred only at Cremophor concentrations above the CMC. PMID- 1454876 TI - Generation of free radicals during photosensitization of hypocrellin A and their effects on cardiac membranes. AB - Hypocrellin A (HA), a peryloquinone derivative, has recently been isolated from a fungus Hypocrella bambusae. This lipid soluble pigment, in combination with phototherapy, has been used to treat many skin diseases including the keloids caused by scalding and burns. We have studied the effects of photosensitized HA on biomembranes using pig heart microsomes. Photosensitization of HA was found to peroxidize the membrane lipids in the cardiac microsomes. The photodamage imposed by HA depended not only on the concentration of HA but also on the time of irradiation and pH of the system. Superoxide dismutase (SOD), ascorbic acid, beta carotene and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) inhibited the lipid peroxidation approximately 50, approximately 50, approximately 30 and approximately 97%, respectively. Spin trapping in combination with EPR spectroscopic techniques was used to identify the reactive free radicals during the photoreaction. Formation of superoxide anion radical, (O2-.), was identified by the SOD-inhibitable DMPO-O2- EPR spectrum. Both SOD and ascorbic acid inhibited the EPR signal intensity in a dose-dependent manner with rate constants of 6.78 x 10(8) M-1 s-1 and 1.82 x 10(4) M-1 s-1, respectively. The lifetime of O2-., under these conditions, was found to be 1.1 s. Photoirradiation of HA yielded a HA free radical with a g = 2.002 which was not suppressed by SOD but in the presence of reductants such as ascorbic acid and catechol the septum was completely suppressed. The increase of the EPR signal intensity and malondialdehyde formation with increasing pH may be due, in part, to the production of predominant *HA- species at high pH which would be more reactive with oxygen to yield O2-.. These results indicate that the lipid peroxidation of the cardiac membranes observed during photooxidation of HA may arise, in part, from the interaction of membrane lipids with reactive species of oxygen and HA free radical produced during the photo-irradiation. PMID- 1454877 TI - Effects of rhodamine 123 in the dark and after irradiation on mitochondrial energy metabolism. AB - Isolated rat liver mitochondria have been used to study the mechanism of toxicity of Rhodamine 123 (Rho 123) in the dark and after irradiation with visible light. We report an inhibition of adenosine 5'-diphosphate phosphorylation which is increased after illumination. In the dark, the first steps of the phosphorylation process (i.e. the entry of substrates into the matrix, the electron transport to oxygen and the creation of the proton gradient) as well as ATPase activity are not significantly perturbed at Rho 123 concentration below 10 micrograms/mL. In contrast, the movements of the phosphate compounds are drastically impaired. Irradiation strengthens the detrimental effects in an oxygen dependent process. The nature of the noxious transient species is not clearly established, but it is suggested that singlet oxygen could be responsible for the observed damage. PMID- 1454878 TI - Merocyanine 540-sensitized photoinactivation of leukemia cells: effects of dose fractionation. AB - The differential sensitivity to merocyanine 540 (MC540)-sensitized photoirradiation of leukemia cells, selected solid tumor cells, and normal pluripotent hematopoietic stem cells has been successfully exploited for the extracorporeal purging of simulated autologous remission bone marrow grafts. In this communication, we compare the effects of fractionated vs continuous irradiation upon the MC540-sensitized photoinactivation of L1210 and K562 leukemia cells. Exposure to MC540 (15 micrograms/mL) and fractionated doses of white light inactivated fewer in vitro clonogenic cells than exposure to an equivalent dose of continuous irradiation, provided the irradiation doses were small (8.1-16.2 kJ/m2) and spaced 1-2 h apart. The dye-sensitized photoinactivation of leukemia cells was enhanced when cells were stored at 4 degrees C instead of 37 degrees C between irradiation periods, most likely in part because the cells were unable to repair sublethal photodynamic damages at the lower temperature. These data suggest that cells can recover from sublethal damage inflicted by the plasma membrane-active photosensitizer, MC540. PMID- 1454879 TI - The effect of systemic cyclosporin A on a hairless mouse model of photoaging. AB - The mechanisms that cause skin wrinkling in response to chronic exposure to sunlight are unknown. We investigated the possibility that wrinkling of Skh-1 hairless mice is associated with an ultraviolet (UV) radiation-induced immunologic alteration. Exposing Skh-1 hairless mice to a regimen of nonerythemal UV-B (290-320 nm) radiation induced skin wrinkles after 6-7 weeks. Concomitant treatment with cyclosporin A decreased the time to the onset of wrinkles to approximately 4 weeks. Exposing HRS/J hairless mice or athymic nude mice to a similar nonerythemal UV-B radiation regimen for 10 weeks failed to induce skin wrinkles. Concomitant administration of cyclosporin A and UV-B radiation for 7 weeks to HRS/J hairless mice induced no skin wrinkles. Ultraviolet-B or UV-B plus cyclosporin A exposure caused increased immunohistochemical staining for Ia and F4/80 antigens in the upper dermis of tissue from Skh-1 mice, as compared to controls. Treating Skh-1 mice with UV-B radiation plus cyclosporin A was also associated with a large increase in the number of CD3+ cells in the dermis. These staining patterns were absent in similarly treated HRS/J hairless mice. Dermal mast cell numbers in Skh-1 mice were 2-3-fold higher than in HRS/J, athymic nude or NSA mice. Treatment with cyclosporin A increased Skh-1 dermal mast cell numbers approximately 2-fold but had no effect on the dermal mast cell numbers in HRS/J or NSA mice. Based on these findings we postulate that UV-B light and cyclosporin A exacerbate an immunological condition in Skh-1 mice, one consequence of which is manifested as skin wrinkles. Thus, the induction of skin wrinkles in this mouse strain may have no relevance to the wrinkles observed in human skin after chronic exposure to sunlight. PMID- 1454880 TI - The hairless mouse model of photoaging: evaluation of the relationship between dermal elastin, collagen, skin thickness and wrinkles. AB - Quantitative and qualitative changes in dermal collagen and elastin occur in response to chronic ultraviolet (UV) irradiation. These changes have been implicated in the genesis of the wrinkling seen in chronically irradiated, or photoaged skin. We examined the relationship between wrinkle formation and changes in dermal structural protein content and type. Skh-1 hairless mice were irradiated with suberythemal doses of UV-B three times a week for up to 20 wk. Visible wrinkling was present after 6-7 wk of irradiation. Dermal elastic fiber content was quantified by color image analysis of paraffin-embedded tissue. There was no significant difference in dermal elastic fiber content between irradiated and age-matched control mice after either 10 or 20 wk of irradiation. The effect of UV-B irradiation on total dermal collagen content, ratio of collagen type III type I, and extent of glycosylation and crosslinking of collagen was no different in irradiated and age-matched control mice after 10 wk of irradiation. Increased epidermal thickness was evident in frozen sections after 6 wk of irradiation, and the thickness increased with continued irradiation. Dermal thickening was evident after 10 wk of irradiation. Sufficient UV-B irradiation will eventually cause changes in dermal elastin and collagen content; however, wrinkle formation precedes such changes. A causal relationship between wrinkle formation and dermal structural protein content changes in Skh-1 hairless mice could not be established in this study. PMID- 1454881 TI - Effects of photodynamic treatment of platelets or endothelial cells in vitro on platelet aggregation. AB - The purpose of this work was to gain insight into the role played by platelets and endothelial cells in the development of thrombogenic vascular events, observed after in vivo photodynamic therapy (PDT), by studying the in vitro effects of PDT on isolated human platelets and cultured human and bovine endothelial cells. Exposure to Photofrin II (PII) and light caused platelets to rapidly lose their ability to aggregate. Photofrin II alone at high concentrations also exerted inhibitory effects on aggregation. Endothelial cells exposed to PII- and phthalocyanine (GaCl-PcS2,3 or Zn-PCS1,2)-mediated PDT released potent platelet anti- and disaggregating activity which could be identified as prostacyclin by the following criteria: a close correlation between the time and dose dependent anti-aggregating effects and released 6-keto-PGF1 alpha (the spontaneous hydrolysis product of PGI2, determined by radioimmunoassay), the inhibition of these effects by indomethacin, accumulation of 6-keto-PGF1 alpha metabolite in the media of cells treated with PDT (as determined by HPLC analysis), and the absence of evidence for significant nitric oxide production. This prostacyclin release occurred following plasma membrane damage. Although no pro-aggregating activity was observed, endothelial cells were found to release considerable amounts of arachidonic acid and prostaglandin F2 alpha in response to PDT. These data, which indicate powerful anti-thrombogenic effects in vitro, are in sharp contrast to the vascular effects of PDT in vivo which are characterized by severe platelet aggregation, and imply that the in vivo effects involve additional components of the vascular system. PMID- 1454882 TI - Levels of reduced pyridine nucleotides and lens photodamage. AB - Since most of the known factors that are associated with cataract formation are oxidative in nature, one would expect that a highly reductive environment might arrest or retard the progress of cataract formation. Reduced nucleotides, both NADH and NADPH, are potent reductants with a large negative redox potential of 320 mV. Lenses of certain species contain high levels of these nucleotides, presumably due to the presence of taxon specific crystallins. We have utilized this situation to investigate whether the levels of reduced pyridine nucleotides modulate photo-oxidative damage to the lens. We have monitored the time dependent loss of tryptophan fluorescence upon photodamage for lenses from guinea pig, rabbit and frog (Rana) that contain high levels of pyridine nucleotides and compared with the lenses from rat, Xenopus and a mutant strain of guinea pig that contain significantly lower amounts of these nucleotides. About 75% and 90% of the initial fluorescence intensity is lost in the case of rat and Xenopus lenses, respectively, after a total of 35 min exposure. Rabbit, guinea pig and frog lenses, under identical conditions, show only about 35-40% loss of the initial fluorescence. It appears that the lenses that contain high levels of reduced nucleotides are less susceptible to photodamage. The observed anti-oxidative role of reduced nucleotides in the lenses indicates the possibility of testing reductants (NADPH, NADH and their functional analogues) as potential candidates to therapeutically intervene in the process of cataractogenesis. PMID- 1454883 TI - Photon emission during cleavage of frog eggs. AB - Emission of light was detected from the surface of embryos of the frog, Rana japonica, during early cleavage by a photon counting and an "analog separation (integrated photons) method". The light-emission from an egg was more than 5.6 x 10(-19) W at the beginning of the first cleavage. PMID- 1454884 TI - Women scientists of the American Physiological Society. PMID- 1454885 TI - The origin, evolution, and distribution of life in the universe. PMID- 1454886 TI - Observations on the utility of couples therapy conducted by a psychoanalyst- transference and countertransference in resistance to analysis. AB - This paper explores the premise that conviction concerning the therapeutic efficacy of psychoanalysis combined with a flexible attitude toward the structure of the analytic situation and the parameters of its techniques facilitates the acceptance of psychoanalysis in suitable cases as the treatment of choice. Clinical data from therapy with couples are presented in support of this premise. PMID- 1454887 TI - Use of the analyst as a fetish. AB - In some cases a gratifying transference fantasy is the subject of progressive analytic work, while in other cases the same type of fantasy eludes investigation, and its enactment causes treatment to become an unproductive endless task. One cause for the latter difficulty can be that the patient uses his or her analyst as a fetish, permitting the distinction between reality and fantasy to remain inconclusive, so that relinquishment of magical expectations does not take place. The particular form of thinking involved in use of the analyst as a fetish is described. The role of illusion, its various clinical manifestations, the countertransference reactions they can evoke, and the technical problems posed are discussed. Special attention is given to the crucial issue of termination. By considering extreme instances in which use of the analyst as a fetish predominates, the author hopes to call attention to a phenomenon that appears to some degree in many, if not all, analyses. PMID- 1454888 TI - Slips of the analyst. AB - Understanding the analyst's work and its vicissitudes has been a major focus of recent psychoanalytic writing. This study on slips of the analyst represents an attempt to advance our understanding of analytic work. The slips described support the view that slips reflect not simply contributions from instinctual life, but active work-related goals of the analyst in carrying out the analytic tasks. Countertransference is discussed as reflected in the disturbance of intentionality betrayed by the occurrence of a slip. The essential role of the analyst's understanding his or her own reactions is emphasized. PMID- 1454889 TI - An example of "character perversion" in a woman. PMID- 1454890 TI - The moral journey of the first Viennese psychoanalysts. AB - By exploring the cultural concerns of Freud's first Viennese disciples, this article explains how these concerns helped inspire both intellectual conviction in Freudianism and inner commitment to the psychoanalytic movement. In this way, it illuminates an important underlying identity between medical practitioners and laypersons within Freud's circle. At the same time, it brings to light the tension between values and science in Viennese psychoanalysis. PMID- 1454891 TI - Cultural variations in emotions: a review. AB - The psychological and anthropological literature on cultural variations in emotions is reviewed. The literature has been interpreted within the framework of a cognitive-process model of emotions. Both cross-cultural differences and similarities were identified in each phase of the emotion process; similarities in 1 phase do not necessarily imply similarities in other phases. Whether cross cultural differences or similarities are found depends to an important degree on the level of description of the emotional phenomena. Cultural differences in emotions appear to be due to differences in event types or schemas, in culture specific appraisal propensities, in behavior repertoires, or in regulation processes. Differences in taxonomies of emotion words sometimes reflect true emotion differences like those just mentioned, but they may also just result from differences in which emotion-process phase serves as the basis for categorization. PMID- 1454892 TI - Sensory and affective components of pain: separation and synthesis. AB - It has become increasingly accepted that pain is not simply a sensation generated by nociceptors, but a perceptual phenomenon with particular emotional qualities. The purpose of this article is to bring together vastly different streams of research on the divisibility of pain into sensory and affective components. Empirical evidence for this divisibility is drawn from recent studies using multivariate statistics, signal detection theory, and unidimensional scaling. An important conclusion is that separable though pain components may be, they are not necessarily independent. In critiquing previous research, new criteria are derived for partitioning pain into sensory and affective components. Finally, speculations are offered as to how these same components might be synthesized on the basis of theories of perceptual organization. PMID- 1454893 TI - Uncontrollability and unpredictability in post-traumatic stress disorder: an animal model. AB - The disturbances observed in animals subjected to unpredictable and uncontrollable aversive events resemble post-traumatic stress disorder (PTSD) symptoms and thus may constitute an animal model of this disorder. It is argued that the similarity between animals' symptoms and those of trauma victims may reflect common etiological factors. Relevant experiments in which animals exhibit generalized fear and arousal, discrete fear of a conditioned stimulus (CS), analgesia, and avoidance are reviewed with the view that these manifestations may be analogous to the PTSD symptom clusters of persistent arousal, reexperiencing, numbing, and avoidance, respectively. Finally, animal paradigms are suggested to test the validity of the model and specific hypotheses are derived from the animal literature regarding trauma variables that are predictive of particular PTSD symptom clusters. PMID- 1454894 TI - Extraversion and vigilance performance: 30 years of inconsistencies. AB - Deteriorating efficiency in detecting critical events is a pervasive phenomenon. It has been asserted that the personality dimension of extraversion-introversion (E-I) could serve as a selection device: Introverts would be superior in sustained attention. A meta-analysis revealed better performance of introverts, but the effect size was small because of a high incidence of inconsistencies. In a subset of the studies, the effect size was much larger: Introverts were superior in overall level of correct detections but not in maintaining efficiency over time. Inconsistent findings may partly have been caused by inappropriate use of univariate analysis of variance in repeated measures designs. The validity of some "classic" findings in the vigilance literature was questioned. The relationship of E-I to electrodermal speed of habituation was discussed. Finally, here also a trend was noted to move to new problems before solving old ones. PMID- 1454895 TI - Psychological compensation: a theoretical framework. AB - The 2 main objectives of this article are to review a variety of literatures in which the concept of compensation is used and to integrate the results of this review into a general framework of compensation. The review focuses on 4 domains of psychological inquiry: compensation for sensory handicaps, cognitive deficits, interpersonal losses, and brain injury. In the proposed framework, underlying dimensions and 4 basic steps in the progression of compensatory behavior are distinguished. The latter include origins, mechanisms, forms, and consequences. Finally, we describe ways in which researchers in particular domains can benefit from the global, process-oriented framework we propose. For most of the areas of compensation research reviewed, investigators can profit from a consideration of a broader selection of dimensions, additional steps in the process, alternative outcomes, and both objective and subjective assessment procedures. PMID- 1454896 TI - Emotional stress and eyewitness memory: a critical review. AB - The eyewitness literature often claims that emotional stress leads to an impairment in memory and, hence, that details of unpleasant emotional events are remembered less accurately than details of neutral or everyday events. A common assumption behind this view is that a decrease in available processing capacity occurs at states of high emotional arousal, which, therefore, leads to less efficient memory processing. The research reviewed here shows that this belief is overly simplistic. Current studies demonstrate striking interactions between type of event, type of detail information, time of test, and type of retrieval information. This article also reviews the literature on memory for stressful events with respect to two major theories: the Yerkes-Dodson law and Easter brook's cue-utilization hypothesis. To account for the findings from real-life studies and laboratory studies, this article discusses the possibility that emotional events receive some preferential processing mediated by factors related to early perceptual processing and late conceptual processing. PMID- 1454897 TI - Feeling good-doing good: a conceptual analysis of the mood at work-organizational spontaneity relationship. AB - Five forms of organizational spontaneity are described (helping co-workers, protecting the organization, making constructive suggestions, developing oneself, and spreading goodwill). Organizational spontaneity is compared with the seemingly analogous constructs of organizational citizenship behavior and prosocial organizational behavior. Based on a selective review of the literature, a multilevel model of spontaneity is presented. Positive mood at work is a pivotal construct in the model and posited as the direct precursor of organizational spontaneity. Primary work-group characteristics, the affective tone of the primary work group, affective disposition, life event history, and contextual characteristics are proposed to have direct or indirect effects, or both, on positive mood at work. Motivational bases of organizational spontaneity also are described. The model and its implications are discussed. PMID- 1454898 TI - Modulatory role of serotonin in neural information processing: implications for human psychopathology. AB - Investigation of the role of 5-hydroxytryptophan (5-HT), which functions as a modulator in the central nervous system, across behavioral contexts suggests that a general principle of transmitter function may be derived that is independent of specific behaviors and specific neural loci. A functional principle of 5-HT action in neural information processing in the central nervous system is proposed. Extremes deviations in 5-HT activity result in biases in information processing that may have direct effects on behavior. Such biases may predispose to pathological conditions such as violent suicide and aggression. PMID- 1454899 TI - Can test statistics in covariance structure analysis be trusted? AB - Covariance structure analysis uses chi 2 goodness-of-fit test statistics whose adequacy is not known. Scientific conclusions based on models may be distorted when researchers violate sample size, variate independence, and distributional assumptions. The behavior of 6 test statistics is evaluated with a Monte Carlo confirmatory factor analysis study. The tests performed dramatically differently under 7 distributional conditions at 6 sample sizes. Two normal-theory tests worked well under some conditions but completely broke down under other conditions. A test that permits homogeneous nonzero kurtoses performed variably. A test that permits heterogeneous marginal kurtoses performed better. A distribution-free test performed spectacularly badly in all conditions at all but the largest sample sizes. The Satorra-Bentler scaled test statistic performed best overall. PMID- 1454900 TI - How to build a baby: II. Conceptual primitives. AB - A mechanism of perceptual analysis by which infants derive meaning from perceptual activity is described. Infants use this mechanism to redescribe perceptual information into image-schematic format. Image-schemas create conceptual structure from the spatial structure of objects and their movements, resulting in notions such as animacy, inanimacy, agency, and containment. These earliest meanings are nonpropositional, analogical representations grounded in the perceptual world of the infant. In contrast with most perceptual processing, which is not analyzed in this fashion, redescription into image-schematic format simplifies perceptual information and makes it potentially accessible for purposes of concept formation and thought. In addition to enabling preverbal thought, image-schemas provide a foundation for language acquisition by creating an interface between the continuous processes of perception and the discrete nature of language. PMID- 1454901 TI - Origins of knowledge. AB - Experiments with young infants provide evidence for early-developing capacities to represent physical objects and to reason about object motion. Early physical reasoning accords with 2 constraints at the center of mature physical conceptions: continuity and solidity. It fails to accord with 2 constraints that may be peripheral to mature conceptions: gravity and inertia. These experiments suggest that cognition develops concurrently with perception and action and that development leads to the enrichment of conceptions around an unchanging core. The experiments challenge claims that cognition develops on a foundation of perceptual or motor experience, that initial conceptions are inappropriate to the world, and that initial conceptions are abandoned or radically changed with the growth of knowledge. PMID- 1454902 TI - How visual imagery interferes with vision. AB - Mental visual imagery interferes with vision: the Perky (1910) effect. Is the effect optical, sensory, perceptual, attentional, or just a response bias? Acuity was measured (in undergraduates and graduates) using target lines, with and without images (of lines). Optics (fixation, pupil size, accommodation), response bias, global attention (effort; diversion of attention to imagery), perceptual assimilation (target incorporation by imagery) and perceptual masking (of target by imagery) all fail to explain the effect. Foveally, local attention plays a limited role, as the Perky effect in divided attention is half that in focused attention, but this interaction vanishes with extrafoveal targets. Images produce primarily sensory interference, mimicking a reduction in target energy. PMID- 1454904 TI - The four elementary forms of sociality: framework for a unified theory of social relations. AB - The motivation, planning, production, comprehension, coordination, and evaluation of human social life may be based largely on combinations of 4 psychological models. In communal sharing, people treat all members of a category as equivalent. In authority ranking, people attend to their positions in a linear ordering. In equality matching, people keep track of the imbalances among them. In market pricing, people orient to ratio values. Cultures use different rules to implement the 4 models. In addition to an array of inductive evidence from many cultures and approaches, the theory has been supported by ethnographic field work and 19 experimental studies using 7 different methods testing 6 different cognitive predictions on a wide range of subjects from 5 cultures. PMID- 1454903 TI - A theory of humor elicitation. AB - This article presents a general theory of humor elicitation that specifies the conditions in which humor is experienced in both social and nonsocial situations. The theory takes into account the interpretation of a stimulus event that is necessary to elicit humor, the difficulty of identifying the humor-eliciting features of this interpretation, and the cognitive elaboration of implications of the event. The influence of these factors is postulated to depend on subjects' information-processing objectives at the time a stimulus event occurs. The theory is used to conceptualize the humor elicited by jokes, witticisms, and social events that are neither intended nor expected to be humorous. Particular attention is given to the cognitive underpinnings of responses to ethnic humor and to the humor that is elicited by one's own behavior in social situations. PMID- 1454905 TI - Development of an instrument to assess learning strategies. AB - Items to measure learning strategies were extracted from students' written narratives about their study and learning habits. A resulting 79-item instrument was administered to 321 graduate and undergraduate students. From factor analysis of the correlation matrix four factors were identified: (I) reflective metacognition, (II) procedural metacognition, (III) rote memorization, and (IV) procrastination. There were significant positive correlations between GPA and Factors I and II and a significant negative correlation between Factor IV and GPA. PMID- 1454906 TI - Value of the Mini-Mental State Examination and informants' data for the detection of dementia in geriatric outpatients. AB - The Dutch version of the Mini-Mental State Examination was administered to 138 elderly patients who were referred to a geriatric outpatient clinic for a variety of reasons. An optimal cut-off point of 24/25 was found for the detection of dementia. At this cut-off point, the Mini-Mental State Examination was 87.6% sensitive and 81.6% specific in detecting dementia. The discriminative validity was influenced by education and by the presence of psychiatric disorders other than dementia. Informants' data showed better sensitivity and specificity than the Mini-Mental State Examination for the detection of dementia. The findings suggest that informants' data are a primary source of information for the detection of dementia in geriatric outpatients. PMID- 1454907 TI - Fantasizers and dissociaters: data on two distinct subgroups of deep trance subjects. AB - This study delineated two subgroups of highly hypnotizable subjects. The first (n = 19) entered trance rapidly, scored high on absorption, and described hypnosis as much like their rich and vivid waking fantasy life. The second subgroup of 15 took time to achieve a deep trance, saw hypnosis as very different from any prior experiences, and were more likely to exhibit amnesia for both hypnotic experience and waking fantasies. PMID- 1454908 TI - Correlations of memory and learning with vision in aged patients before and after a cataract operation. AB - The connection between memory and learning with vision was investigated by studying 100 cataract operation patients, aged 71 to 76 years, 25 of them being men and 75 women. The cataract operation restored sufficient acuity of vision for reading (minimum E-test value 0.40) to 79% of the subjects. Short-term memory was studied with series of numbers, homogenic and heterogenic inhibition, and long sentences. Learning was tested with paired-associate learning and word learning. Psychological symptoms were measured on the Brief Psychiatric Rating Scale and personality on the Mini-Mult MMPI. Memory and learning improved significantly when vision was normalized after the cataract operation. Poor memory and learning scores correlated with monocular vision before the operation and with defects in the field of vision, due to glaucoma and exceeding 20%, postsurgery. Monocular vision and defects in the visual field caused a continuous sense of abnormalness, which impaired old people's ability to concentrate on tasks of memory and learning. Cerebrovascular disturbances, beginning dementia, and moderate psychological symptoms obstructed memory and learning on both test rounds. Depression was the most important psychological symptom contributing to poor memory and learning scores after the cataract operation. The memory and learning defects mainly reflected disturbances in memorizing. PMID- 1454909 TI - Role of personality characteristics in coping behaviors. AB - The relations between coping behaviors and personality characteristics (introversion/extroversion) were examined in 176 Japanese female college students. Multiple regression analysis indicated that extrovertive individuals more often used not only seeking social support but also avoidance than did introvertive subjects. An implication for further research would be to analyze the interactions between personality influences and situational factors in coping behaviors. PMID- 1454910 TI - Imaginal, sensory, and cognitive experience in spontaneous recovery from alcoholism. AB - Although alcoholism is often regarded as an intractable disorder that requires intensive treatment, studies of the natural history of alcoholism indicate that unaided, spontaneous recovery may be the most common pathway to remission from alcoholism. Negative environmental consequences of alcoholic drinking have been invoked to explain spontaneous recovery, but a more compelling reason for sudden changes in drinking behavior concerns shifts in the personal meanings surrounding alcohol use. Extensive interviews in a multimodal format were conducted with two groups of alcoholics: one group comprised of 7 subjects who spontaneously recovered without treatment and the other group comprised of 9 people who believed formal treatment was necessary to abstain from drinking. Spontaneously recovered alcoholics reported experiencing vivid sensations and images at the time they decided to quit drinking, and they reported subsequent transformations of their personal identities. Active alcoholics reported no comparable experiences in imaginal, sensory, and cognitive modalities. Implications of the results for current alcoholism treatments are discussed. PMID- 1454911 TI - Relationship between MCMI-II scales and normal personality traits. AB - We correlated MCMI-II and 16 PF profiles of 145 couples in outpatient marital therapy and noted significant associations between these tests that were consistently and logically related to constructs which underlie the meaning of the MCMI-II scales. This provided good concurrent validity for both the Personality and Clinical Scales of the MCMI-II. These results add credence to research designed to study Millon's basic styles in normal populations. PMID- 1454912 TI - Bipolar depression as the prelude to schizoaffective disorder. AB - Contending that the mind of a creative person is often characterized by thin boundaries between the ego and the unconscious, this paper proposes how, on the manic side of bipolar depression, a creative ego may temporarily make great strides in intellectuality and creativity. However, as this process proceeds, a creative ego may lose its boundaries with the unconscious, and a schizoaffective disorder may emerge. PMID- 1454913 TI - Collectivism-individualism and rates of personal violence (suicide and homicide). PMID- 1454914 TI - International comparisons: selected mental health data. AB - The data set from the Organization for Economic Cooperation and Development (OECD) was explored to investigate the relationship of gross domestic product (which provides an indication of the wealth of a country) and the provision of psychiatric services (specifically inpatient psychiatric services) in selected OECD countries. Gross domestic product per capita correlated .84 with expenditure per capita on psychiatric hospitals but r was zero between number of beds per 1000 population and length of stay. PMID- 1454915 TI - Gender and sex-role differences in young adult reactions towards "newborns" in a pretend situation. AB - 104 college students were asked to fill out a questionnaire on sex-role orientation, act out a scene as a parent with a newborn baby (doll), rate their attitudes toward the baby using a semantic differential scale of 19 adjective pairs, and write an open-ended statement about the baby's future. Analysis indicated few differences in how men and women reacted to or described boy and girl babies and most of the variability in scores could be accounted for by interactions involving sex-role orientation. Sex-stereotyped women typically gave ratings similar to those given by androgynous women while sex-stereotyped men, when they differed from androgynous men, generally gave less positive ratings. PMID- 1454916 TI - Decriminalization of suicide in Canada and suicide rates. PMID- 1454917 TI - Extended normative data for the Logical Memory subtests of the Wechsler Memory Scale--Revised: responses from a sample of cognitively intact elderly medical patients. AB - 66 cognitively intact geriatric medical patients (ages 70 to 99; M = 77 yr.) were given the Logical Memory subtests of the Wechsler Memory Scale--Revised to extend normative data. 43 women and 23 men, 35 white and 31 black persons made up this urban geriatric sample. A review of patients' medical histories and Mattis' Dementia Rating scores of 129 or greater were used to ensure a sample of cognitively intact patients. Analyses showed that Logical Memory scores were uncorrelated with education, race, sex, or age. PMID- 1454918 TI - Grouping of children's helping behaviour. AB - 215 school children aged 9 to 12 yr. were grouped according to their helping behaviour. The following variables were measured: helping, empathy, altruism, morality, attribution of responsibility, cognitive readiness to help, willingness to help, social desirability, and abstract thinking. In a factor analysis age and sex were included. Five factors were extracted and interpreted: empathetic helping, socially desirable helping, cognitive helping, intentionality, and rational helping. According to grouping analysis these five factors were weighted differently, and three groups were identified, (1) real helpers with high empathy, altruism, morality, and cognitive readiness to help, (2) normative helpers, motivated by social desirability or cognitive factors with poor empathy level, and (3) cognitively premature, rational helpers with poor empathy and with weak social desirability. PMID- 1454919 TI - Capital punishment in Texas: comparison of some factors shared by 50 convicted murderers and their victims. AB - The mean age of 50 convicted murderers at time of execution was compared to the mean age of their victims at time of death. The mean ages compared were not significantly different. PMID- 1454920 TI - Depression, self-esteem, suicide ideation, death anxiety, and GPA in high school students of divorced and nondivorced parents. AB - 131 subjects from a small north central Kansas high school participated and completed the Beck Depression Scale, Coopersmith Self-esteem Inventory short form with the Lie scale included, the Death Anxiety Scale, and the first 11 questions of the Beck Scale of Suicide Ideation. Background information collected from each subject included age, grade, marital status of parents, and sex. Grade point averages (on a 4-point scale) were taken from the students' files. On death anxiety girls had a significantly higher mean than boys while freshmen's and sophomores' scores were significantly higher than those of juniors and seniors but there was no difference between means of students of divorced and nondivorced parents. On self-esteem and GPA children of divorced parents scored significantly lower than children of nondivorced parents, but there was no difference between the sexes on self-esteem. On GPA girls scored significantly higher than boys. On depression the children of divorced parents scored higher than children of nondivorced parents but there was no sex difference. PMID- 1454921 TI - University students' perceptions of deaf parents. AB - A methodology for assessing attitudes toward nontraditional parents was developed. 54 university students with a mean age of 26.5 yr. (SD = 10.2 yr.) participated in a study which assessed attitudes toward deaf parents by asking subjects to rate the adoptive suitability of an unmarried applicant based on a scenario describing the individual as a deaf woman, deaf man, hearing woman, or hearing man. Women were perceived as more suitable to adopt daughters, and men were perceived as more suitable to adopt sons. Applicants' hearing status and gender influenced perceived suitability to adopt a son but not a daughter. PMID- 1454922 TI - Development and testing of the AIDS Psychosocial Scale. AB - The dramatic spread of AIDS globally has placed it high on the world health agenda. Since no medical or technological solution to the problem is near at hand and given the fact that the HIV virus is heavily reliant on human sexual behaviours for transmission, tackling the problem of AIDS rests on addressing change of sexual behaviour. Various psychosocial factors have been implicated as mediating between adequate knowledge and behaviour change, given the poor correlation between the two variables. The present study was aimed at developing and testing a scale to measure various psychosocial factors, including self concept, defenses of denial, repression and rationalisation, peer pressure, and perceived empowerment expressed in locus of control and self-efficacy. Two studies are reported in which students at the University of the Western Cape, South Africa participated. Various statistical analyses in the two phases indicated that the AIDS Psychosocial Scale was sufficiently reliable and valid for use in examining psychosocial mediation in the AIDS area. PMID- 1454923 TI - Crisis calls and lunar cycles: a twenty-year review. AB - 12 studies are reviewed that have examined the relationships among crisis calls to police stations, poison centers, and crisis intervention centers and the synodic lunar cycle. On the basis of the studies considered it is concluded that no good foundation exists for the belief that lunar phase is related to the frequency of crisis calls. In addition, there is no evidence whatsoever for the contention that calls of a more emotional or "out-of-control" nature occur more often at the full moon. PMID- 1454924 TI - Human sympathy-groups: cross-cultural data. PMID- 1454925 TI - Suicide and lunar cycles: a critical review over 28 years. AB - 20 studies which have examined the relations between completed suicide or attempted suicide and suicide threats with the synodic lunar cycle are reviewed. Most studies indicated no relation between lunar phase and the measures of suicide. The positive findings conflicted, have not been replicated, or were confounded with variables such as season, weekday, weather, or holidays. It is concluded that there is insufficient evidence for assuming a relationship between the synodic lunar cycle and completed or attempted suicide. PMID- 1454926 TI - The Bem Sex-role Inventory as an index of response tendencies to scales in Likert format. AB - 7 women, classified as Masculine on the basis of their scores on the Bem Sex-role Inventory, tended to use the extreme values of agree strongly and disagree strongly on the Likert format associated with the East-West Questionnaire more frequently than did women classified as Feminine, Androgynous, or Undifferentiated (ns = 39, 31, and 21, respectively). The Undifferentiated women were inclined to use the moderate response alternatives. The 73 men used the no opinion response option significantly more than did the 98 women. These findings suggest that strength of beliefs as measured on scales in Likert format may be an index of sex-role preference. PMID- 1454927 TI - Narcissism and object relations. AB - Questionnaire measures of the narcissistic personality disorder can predict healthy and unhealthy self-functioning. That this outcome might support Heinz Kohut's psychoanalytic psychology of the self was tested in a sample of 354 undergraduates. In canonical correlations, factors from the Narcissistic Personality Inventory were associated more strongly with grandiose than with idealizing immaturities in Kohut's bipolar self, while difficulties in interpersonal relationships (i.e., poor object relations) were associated more strongly with idealizing deficits. Zero-order and partial correlational data were congruent with Kohut's hypothesis that self-grandiosity can include elements of both "pathology" and relative mental health, but canonical correlations did not support Kohut's claim that narcissism can be described in a bidimensional self structure. PMID- 1454928 TI - College vs junior high school students' knowledge of alcohol as a teratogen. AB - This study assessed knowledge possessed by male and female junior high school and college students (N = 422) about the teratogenic effects of alcohol. Although most students were aware that alcohol is a teratogenic substance, they demonstrated little knowledge of the nature and timing of possible specific negative effects. PMID- 1454929 TI - Contributions to the history of psychology: XC. Evolutionary biology and heritable traits (with reference to oriental-white-black differences): the 1989 AAAS paper. AB - Genetic distance estimates calculated from DNA sequencing indicate that in years since emergence from the ancestral hominid line, Mongoloids = 41,000, Caucasoids = 110,000, and Negroids = 200,000. Data also show that this succession is matched by numerous other differences such that Mongoloids > Caucasoids > Negroids in brain size and intelligence (cranial capacity = 1448, 1408, 1334 cm3; brain weight = 1351, 1336, 1286 gm.; millions of excess neurons = 8900, 8650, 8550; IQ = 107, 100, 85); maturational delay (age to walk alone, age of first intercourse, age of death); sexual restraint (ovulation rate, intercourse frequencies, sexually transmitted diseases including AIDS); quiescent temperament (aggressiveness, anxiety, sociability); and social organization (law abidingness, marital stability, mental health). This pattern is ordered by a theory of r/K reproductive strategies in which Mongoloids are posited to be more K-selected than Caucasoids and especially more than Negroids. (K-selected reproductive strategies emphasize parental care and are to be contrasted with r-selected strategies which emphasize fecundity, the bioenergetic trade-off between which is postulated to underlie cross-species differences in brain size, speed of maturation, reproductive effort, and longevity.) It is suggested that this pattern came about because the ice ages exerted greater selection pressures on the later emerging populations to produce larger brains, longer lives, and more K like behavior. One theoretical possibility is that evolution is progressive and that some populations are more "advanced" than others. Predictions are made concerning economic projections and the spread of AIDS. PMID- 1454930 TI - Meaning of craving in research on addiction. AB - The meaning of the word craving varies as illustrated by Kozlowski and Wilkinson's reports of ambiguities in use amongst cigarette smokers. We extended this line of investigation to problem drinkers who sought a goal of controlled drinking versus abstinence, to professionals involved in the addictions area, and to university students. Significant differences in meaning were noted particularly among the problem drinkers (N = 256 between 17 and 60 years of age). Reasons for this are offered. PMID- 1454931 TI - Chaos, an omen of transcendence in the psychotherapeutic process. AB - Here some of the basic ideas assembled under the recently coined term chaos theory are applied to the process of psychotherapy. Utilizing some ideas from chaos theory, "chaos" is defined in psychological terms as a state of overwhelming anxiety and is interpreted as the first indication of potential psychological growth. The concepts of Analytical Psychology and the modality of sandtray therapy are used to illustrate the type of therapeutic approach this theoretical work proposes in the transcendent cycle. Psychotherapy simply facilitates a transformation, wherein clients are guided through the chaos they are experiencing so that they may grow beyond their current psychological limitations. PMID- 1454932 TI - Suicide, homicide and unemployment: a methodological note. AB - In multiple regression analyses, the monthly time-series suicide and homicide rates for the USA from 1957-1986 were associated with unemployment and marriage rates. In contrast, annual time-series suicide and homicide rates were not as strongly associated with the social variables. PMID- 1454933 TI - Ability and personality correlates of children's attitudes and aspirations. AB - This study examined to what extent personality types are related to children's attitudes and aspirations after taking into account relationships between ability and the attitude and aspiration measures. Data were collected from 500 12-yr.-old Australian children. In the analysis the children were classified into four personality groups who were labeled as extravert-adjusted, extravert-anxious, introvert-adjusted, and introvert-anxious. The findings suggest the general proposition that children's personality types have strong associations with school-related attitudes after taking into account associations between children's intellectual ability and their attitudes. In contrast, children's personalities tended not to be related to measures of educational and occupational aspirations. PMID- 1454934 TI - Role reward and role stress in managerial and professional women. AB - The importance of balancing personal and work demands has become increasingly relevant in recent years as large numbers of women move into the labour market full time. The present study was designed to examine differences in role rewards and stress amongst a group of 163 managerial and professional women. Subjects completed a questionnaire about the stress and rewards associated with their work and family roles. Although no significant differences were found between managerial and professional women, the mean scores indicated the role of employee is both the most rewarding and the most stressful. Findings are discussed in terms of sample occupation and changing home-work patterns. PMID- 1454935 TI - Problem-solving appraisal in the association of life stress and depression: a South African study. AB - This study focuses on the role that appraisal of problem-solving skills plays in the relationship of stress to distress. 450 black South African university students completed the Life Experiences Survey, the Problem Solving Inventory, and the Centre for Epidemiological Studies Depression Scale. Multiple regression analysis indicated a direct effect for problem-solving appraisal on depression, but no support could be found for the stress-buffering effects of problem-solving appraisal. PMID- 1454936 TI - A short form of the Wechsler Preschool and Primary Scale of Intelligence for use in Iran. AB - Data from the standardization of the Wechsler Preschool and Primary Scale of Intelligence in Shiraz, Iran (193 girls, 203 boys 4 to 6.5 yr. old) were used to develop a short form. Four subtests (Vocabulary, Arithmetic, Picture Completion, and Block Design) were selected on the basis of their high correlations with Full Scale IQs. The validity coefficients were high and significant. The standard errors for the short form were 4.0 to 6.0 points. The short form classified correctly about 73% of the subjects by category of intelligence but tended to underestimate the IQs of subjects of high intelligence and to overestimate the IQs of subjects with low intelligence. Further work is required. PMID- 1454937 TI - Relationship between the Millon Clinical Multiaxial Inventory and the Millon-II: value of scales for Aggressive and Self-defeating personalities in Posttraumatic Stress Disorder. AB - This study addressed two issues, the interrelationship between the Millon Clinical Multiaxial Inventory (MCMI) and the Millon II (MCMI-II) and the value of the new personality scales, Aggressive and Self-defeating, in a sample with diagnoses of combat-related Posttraumatic Stress Disorder. 100 confirmed cases of combat-related Posttraumatic Stress Disorder were given a battery of measures including both Millon inventories and the Minnesota Multiphasic Personality Inventory (basic scales and selected subscales). They were rated on discharge status during a structured treatment program. Basic treatment and background information were also obtained. Analysis showed scores on the MCMI-II scales were higher but generally reflective of MCMI scales and that the Self-defeating personality style tends to be reflective of greater psychopathology, suicidal problems, treatment/disposition difficulties, overreporting of symptoms, and intensity of problems. Discussion encouraged the use of the MCMI-II with special emphasis given to the Self-defeating style in this group with Posttraumatic Stress Disorder. PMID- 1454938 TI - Superiority of the keyword method for backward recall in vocabulary acquisition. PMID- 1454939 TI - Self-esteem, anxiety, and drug use. AB - This pilot study evaluated the relationship between self-esteem, anxiety, and drug use in a nonclinical sample of 30 men, ages 16 to 43 years, who completed and returned inventories on self-esteem, trait anxiety, and drug use which they had received by mail. Analysis showed a significant negative correlation between self-esteem and drug use and a significant positive correlation between trait anxiety and drug use. Also, a significant negative correlation was found between self-esteem and trait anxiety. Implications are discussed. PMID- 1454940 TI - Depression, self-esteem, suicide ideation, and GPAs of high school students at risk. AB - 131 subjects completed the Beck Depression Inventory, Coopersmith's Self-esteem Inventory--Short Form, the first 11 questions of the Beck Scale of Suicide Ideation, and gave some background information. The students receiving free or reduced-cost lunches scored lower on self-esteem, while students who had been absent more than 15 times scored higher on depression and suicide ideation and had lower GPAs than students who were not absent as often but had similar scores on self-esteem. Students who were below the 25th percentile on the SRA Composite score had lower GPAs. 9 students in special education in Learning Disabilities and Behavioral Disordered categories had scores similar to those of 121 regular education students on depression, self-esteem, suicide ideation, and GPA. Indicators for children at-risk provide clues about how children think about themselves, others, and the world in which they live. PMID- 1454941 TI - Self-perception of asthmatic children and modification through self-management programmes. AB - To examine the influence of asthma on patients' self-perceptions, 48 children with light to moderate asthma and 41 healthy children were selected to complete Harter's Self-perception Profile for children. No differences between the groups were observed. Then, to assess the effects of a psychological asthma treatment programme on self-perception, 27 of the asthmatic children were selected and allocated to three groups of 9 patients. The first of these groups received an asthma self-management programme, the second received that programme plus training in progressive relaxation, and the third (as control) only standard pharmacological treatment. Immediately after intervention and at 6- and 12-mo. follow-ups subjects again completed Harter's profile on which no significant changes were observed. PMID- 1454942 TI - Does spousal participation in Gamblers Anonymous benefit compulsive gamblers? AB - Extent of gambling-free periods was compared for 90 compulsive gamblers, 44 with spouses who participated in Gamblers Anonymous and 46 with spouses who did not. Although the results were in the direction of a beneficial effect of spousal participation, the relationship was statistically nonsignificant. PMID- 1454943 TI - Use of formal assessments among providers of residential services for the seriously mentally ill. AB - A survey of use of formal scales in assessment was sent to 1381 agencies that provide residential services to the seriously mentally ill. 271 residential agencies responded. A majority of respondents who used formal assessments used in house measures. Scales were used most often in client care decisions. A substantial minority of respondents reported being somewhat or very dissatisfied with existing scales. Lack of predictive ability and staff time required were the most frequently cited difficulties. The study indicates a need for better assessments to aid client-care planning, and promote interagency communication. PMID- 1454945 TI - Psychological development in men: generativity and involvement with young children. AB - The personality development of 50 white men was investigated in terms of Eriksonian generativity and involvement with young children. Generativity was not related to caregiving; however, it was associated with social involvement. Generativity was also associated with several aspects of male personality including self-esteem, locus of control, and instrumentality. PMID- 1454944 TI - Birth order, neuroticism, and psychoticism among Iranian children. AB - To investigate the effects of birth order, parents' education, and parents' occupation on four dimensions of the Junior Eysenck Personality Questionnaire, 262 elementary school students (100 boys and 162 girls) were selected randomly from four elementary schools in Shiraz. Analyses showed the main effects of birth order were significant on Neuroticism and Lie scales. Further, the effects of mothers' occupation on the Lie scale and fathers' education on the Neuroticism scale were significant. PMID- 1454946 TI - Sex differences in depression of Iranian adolescents. AB - The purpose of this study was to investigate sex differences on a depression scale for Iranian adolescents. High school students (100 girls and 100 boys), selected randomly from four high schools in Shiraz, completed the Zung Self rating Depression Scale. Analysis showed no significant differences on the five subscales of Zung's depression scale for boys and for girls. Also, there were no sex differences on the total score for depression. However, comparisons with Byrne's groups of British boys and girls indicated differences for Iranian boys and girls on 2 individual items reached significance, whereas for the British groups differences were significant for 11 of the 20 items. PMID- 1454947 TI - Psychiatric and alcoholic admissions do not occur disproportionately close to patients' birthdays. AB - The relationship between admission dates and patients' birthdays was examined for 200 psychiatric and 200 alcoholic patients from a Veterans Affairs Medical Center. Chi-squared analyses indicated that admission dates for subjects of both populations did not occur disproportionately close to their birthdays. PMID- 1454948 TI - Relation of parental education and life status to academic achievement by Xhosa children. AB - This study investigated the relationship between parental education and academic achievement of 1021 Xhosa pupils (369 boys and 652 girls) whose ages ranged from 13 to 17 years (M age, 15.6 yr.). The sample included 712 children for whom both parents were alive and 308 children for whom either or both parents were deceased. Children were chosen at random from the Standard 7/Year 9 population of Transkei, South Africa. A simple questionnaire was administered students to identify whether one or both parents were dead or both parents were living. A second questionnaire was administered parents or parent surrogates to obtain their formal education. The marks obtained by the pupils in the Standard 7 external examination conducted by the Department of Education of the Government of Transkei in seven subject areas were aggregated as the criterion measure. Analysis of variance showed significant effects of parental education on academic achievement of children regardless of whether the children's parents were deceased or alive. PMID- 1454949 TI - Feminism and anorectic tendencies in college women. AB - Anorexia is a debilitating disorder which affects significant numbers of young women. Brumberg has suggested a causal relationship in young women between feminism and anorexia. In this study, traditional-aged female college students completed the Attitudes Toward Women Scale and the Eating Attitudes Test. The hypothesized relationship between feminism and anorexia was not found. PMID- 1454950 TI - Artistic orientation as a clinical indicator of chronic career indecision in adult children and grandchildren of alcoholics. AB - This study has empirically assessed whether artistic orientation and avoidance are good predictors of chronic career indecision for college-attending adult children and grandchildren of alcoholics. The sample consisted of 143 freshman and sophomore introductory psychology students attending a county college in the northeast. Osipow's Career Decision Scale total scores of artistically oriented children and grandchildren of alcoholics were not significantly higher than scores of those who were not artistic. As predicted, the Career Decision Scale total scores of avoidant subjects were significantly higher than those of nonavoidant subjects. As expected in both instances, no differences were found between artistic subjects and nonartistic subjects or between the avoidant and nonavoidant subjects. The findings suggest (1) that the artistic career-undecided children of alcoholics observed by Schumrum and Hartman in 1988 were, in fact, members of a broader avoidant group and (2) that the relationship between career indecision and avoidant personality style does vary according to family status of whether subjects are adult children and grandchildren of alcoholics. PMID- 1454951 TI - Positive and negative social support in a chronic illness. AB - A measure of social support was developed and administered to 207 patients with chronic fatigue syndrome. Positive social support was related to anxiety, and negative social support was related to both anxiety and depression. PMID- 1454952 TI - Gender differences in the personality features of British managers. AB - In this study were examined the personality profiles of 132 British managers from the civil services, using the 16 PF. The data were compared to norms for the British adult population. The results suggested that managers scored higher on traits associated with intelligence, dominance, confidence, and extroversion. This pattern did not differ as a function of gender. Gender differences apparent in the general population were hardly evident among managers. Finally, the strength of traits associated with management increased as a function of the managerial grade. Yet this pattern was more distinct among men than women. PMID- 1454953 TI - Interaction of instructions with the recall strategy actually used in a paired associates learning task. AB - Previous research suggests that interactive imagery produces memory performance superior to separation imagery, although the effects of instructions are less clear. Paired-associate learning was used to examine the effects of instructions (general memory, separation imagery, and interactive imagery) on recall, the frequency of using memory strategies (nonimaginal, separate image, and interactive image), and strategies' effectiveness. The numbers of correctly recalled items were fewer for subjects given general memory instructions than for subjects given separation or interactive imagery instructions which were not different from each other. Subjects reported using a variety of strategies. However, subjects given separation imagery instructions were more likely to report an interactive image than a separate image, and equally as likely to use interactive imagery as subjects given interactive imagery instructions. The present data suggest that subjects can effectively use a variety of memory strategies. PMID- 1454954 TI - Using humor in psychotherapy with a sex offender. AB - Humor was used during psychotherapy with a 22-year-old child molester. The humor appeared to help establish rapport and led to his admission of desires to rape and torture adult women. Here exchange of humor seemed to be a helpful adjunct to psychotherapy. PMID- 1454955 TI - Hemisphericity style and belief in ESP. AB - 108 students were classified as preferring either a style of left or right hemisphericity using Zenhausern's Preference Questionnaire. The students then completed two scales designed to measure belief in extrasensory perception (ESP). Students who scored as preferring a right style scored higher on belief in ESP than those who preferred a left style. The results are consistent with previous findings which suggest a connection between right hemisphere functions (e.g., imagery) and belief in ESP. PMID- 1454956 TI - An experimental analysis of classically conditioned nausea during cancer chemotherapy. AB - This study investigated classical conditioning in women undergoing outpatient adjuvant chemotherapy for breast cancer. Breast cancer chemotherapy outpatients were randomly assigned either to an Experimental Group (exposed to a distinctive stimulus before each infusion of chemotherapy) or to a Control Group. After repeated infusions of chemotherapy, patients' responses to the experimental stimulus were assessed in a location not associated with chemotherapy. Experimental Group patients had increased nausea (self-reported on a visual analog scale) following the presentation of the experimental stimulus at this test trial, whereas Control Group patients did not. Two other measures of nausea corroborated these results. Post hoc statistical analyses confirmed predictions based on conditioning theory. This conditioning model of anticipatory nausea bears witness to the relevance of classical conditioning in clinical medicine. PMID- 1454957 TI - The concept of latent inhibition and its application to psychosomatic medicine. PMID- 1454958 TI - Consistent sex differences in cortisol responses to psychological stress. AB - In four independent studies, sex differences in cortisol responses to psychological stress were investigated in healthy adolescents and adults (total n = 153). Public speaking and mental arithmetic in front of an audience (Studies 1 3) reliably induced increases in free cortisol levels in both sexes with 2- to 4 fold increases above baseline levels. Mean cortisol responses were 1.5- to 2-fold higher in men compared with women. In Study 3, cortisol profiles were additionally investigated after human corticotropin-releasing hormone (h-CRH) and bicycle ergometry until exhaustion. Here, both sexes showed very similar adrenocortical responses. Furthermore, men showed elevated cortisol levels in anticipation of the psychological stress situation without actually having to perform the tasks (Study 4). Under this condition cortisol concentration was unchanged or decreased in women. From these data we conclude that the observed sex difference does not reflect an overall lower responsiveness of the female adrenal cortex. Although these studies do not provide conclusive data, we suggest sex differences in cognitive and/or emotional responses to distressing psychosocial situations which in turn may influence cortisol secretion. PMID- 1454959 TI - Medical and psychiatric symptoms in women with childhood sexual abuse. AB - Although there is increasing awareness of the short-term psychological and social adaptations to childhood sexual abuse, little is known about the long-term effects of such abuse, particularly its effect on subsequent medical utilization and the experience and reporting of physical symptoms. We re-analyzed data from a previous study of 100 women scheduled for diagnostic laparoscopy (50 for chronic pain, 50 for tubal ligation or infertility evaluation) who received structured, physician-administered psychiatric and sexual abuse interviews. Women were regrouped by severity of childhood sexual abuse, and we compared the groups with respect to lifetime psychiatric diagnoses and medically unexplained symptom patterns. Unadjusted odds ratios showed that risk for lifetime diagnoses of major depression, panic disorder, phobia, somatization disorder and drug abuse, and current diagnoses of major depression and somatoform pain disorder were significantly higher in the severely abused group compared with women with no abuse or less severe abuse. Logistic regression analysis demonstrated that number of somatization symptoms, lifetime panic disorder and drug dependence were predictive of a prior history of severe childhood sexual abuse. Psychiatric disorders and medical symptoms, particularly chronic pelvic pain, are common in women with histories of severe childhood sexual abuse. Clinicians should inquire about childhood sexual and physical abuse experiences in patients with multiple medical and psychiatric symptoms, particularly patients with chronic pelvic pain. PMID- 1454960 TI - Eating habits and eating disorders during pregnancy. AB - A general population sample of 100 primigravid women was studied prospectively to describe the changes in eating that occur in pregnancy with particular reference to cravings and aversions and the behavior and attitudes characteristic of clinical eating disorders. Assessment was by standardized interview. Dietary cravings and aversions were found to be common and largely confined to early pregnancy. Eating disorder features decreased in severity early in pregnancy but increased later on. Dietary cravings rarely resulted in episodes of overeating like those seen in patients with eating disorders. In this study of a general population sample, no evidence was found of a relationship between pregnancy outcome and the severity of eating disorder features prior to pregnancy. PMID- 1454961 TI - Lymphocyte subset and cellular immune responses to a brief experimental stressor. AB - To evaluate effects of acute mental stress on aspects of cellular immunity, lymphocyte populations and phytohemagglutinin (PHA)-stimulated T-cell mitogenesis were measured in 33 healthy young men, both before and immediately following subjects' performance of a frustrating, 21-minute laboratory task (Stroop test). Relative to baseline evaluations, post-task measurements showed a significant reduction in mitogenesis and alterations in various circulating lymphocyte populations; the latter included a diminished T-helper/T-suppressor cell ratio and an elevation in the number of natural killer cells. Eleven subjects assigned to a control (unstressed) condition exhibited no changes in lymphocyte populations, but did show an increase in T-cell proliferation, compared with pretask measurements. PMID- 1454962 TI - Acute psychological stressors and short-term immune changes: what, why, for whom, and to what extent? PMID- 1454963 TI - Do cardiovascular responses to laboratory stress relate to ambulatory blood pressure levels?: Yes, in some of the people, some of the time. AB - Because the correspondence between laboratory measures of blood pressure and heart rate responses to stress and ambulatory measures is less than optimal, this study tested two hypotheses: Are ambulatory measures of blood pressure elevated during periods of perceived stress, relative to no stress? Are ambulatory blood pressures elevated during perceived stress among those individuals who exhibit elevated blood pressure and heart rate responses to laboratory stress? These questions were addressed in a sample of employed, middle-aged men and premenopausal and postmenopausal women, who vary in reproductive hormone status, and in risk for coronary heart disease. All participants performed a series of laboratory studies while their physiological parameters were monitored and then wore an ambulatory blood pressure monitor for a day and a half. This monitor recorded blood pressure every half hour during the waking hours and at the same time the participants assessed their mood states. After excluding participants who reported no variability in stress levels, those who were cardiovascular reactors to a laboratory speech task exhibited elevated ambulatory blood pressure levels during periods of perceived stress. Furthermore, in general, periods of perceived stress were associated on a within subject basis with elevated ambulatory blood pressure. These results suggest that the correspondence between laboratory and field measures of blood pressure would be improved by taking into account the environmental circumstances during the ambulatory assessments and the person characteristics of reactor-nonreactor to laboratory stress. PMID- 1454964 TI - Repressive coping and blood lipids in men and women. AB - Studies have suggested that a repressive coping style, characterized by defensiveness against negative emotions, may be related to several adverse health outcomes. This study examined whether repressive coping is associated with blood lipids, and whether this association is influenced by age or sex. One hundred fourteen healthy adults completed the Marlowe-Crowne scale (MC) and the Bendig version of the Taylor Manifest Anxiety scale (TMAS) prior to having their blood drawn after an overnight fast. Hierarchical regression analyses showed a significant interaction of sex, MC, and TMAS on total cholesterol (F(1, 104) = 4.41, p < 0.05), after controlling for the influence of age, body mass index, and other main effects and interactions. Results showed that male repressors (high MC; low TMAS) had the highest cholesterol levels, while truly low anxious males (low MC; low TMAS) had the lowest levels. The opposite pattern was noted for women. There were no interactive effects of age and coping style on lipids. The results suggest that males who repress negative emotions may be at greater risk for atherosclerotic diseases. PMID- 1454965 TI - The multi-dimensional nature of active coping: differential effects of effort and enhanced control on cardiovascular reactivity. AB - Some studies show that enhanced control increases cardiovascular reactivity; other studies show decreases. This disparity may be due to a confound: enhanced control may reduce reactivity, but effort accompanying active coping may increase it. The present study was designed to vary level of control and availability of active coping responses, while maintaining effort constant. Sixty female undergraduates performed word-search puzzles while blood pressure and heart rate were monitored. They were divided into three groups: In condition 1, reinforcement was contingent on the subjects' performance only; in conditions 2 and 3, reinforcement was contingent on the joint performance of the subject and a poorly performing confederate. In condition 2, subjects could help their partners (active coping); in condition 3, they could not (passive coping). Effort was constant across groups. Cardiovascular responses were significantly greater in the passive coping condition than in the other two, indicating that with effort held constant, enhanced control diminishes reactivity. PMID- 1454967 TI - The concept of psychosomatic disorder. AB - The clinical concepts related to the assessment of psychosocial factors in the medically ill are reviewed, with particular reference to the DSM-III-R categories of adjustment disorders, psychological factors affecting physical conditions, and somatoform disorders. The clinical and heuristic value of the concepts of psychosomatic disorder and abnormal illness behavior is underscored. PMID- 1454966 TI - Late luteal phase dysphoric disorder. PMID- 1454968 TI - Psychopharmacological agents in physical disorders. AB - Psychotropic drugs act on multiple organ systems, but their intended action is related to their effect on neurohormones and receptors in the limbic area of the brain. These drugs are also employed with benefit in a number of diverse physical disorders including immunological (arthritis), gastrointestinal (peptic ulcer, ulcerative colitis), neurological (epilepsy), and hematological (leukopenia) conditions. While their clinical efficacy enhances our armamentarium to treat these disorders, understanding their mode of action in treating the physically ill patients may yield the missing link between the psyche and the soma. PMID- 1454969 TI - Role of early developmental factors in susceptibility to disease. AB - Early developmental factors implicated in subsequent infant and child development are presented. The orientation adopted emphasizes both the interplay between constitutional and environmental factors and the mutual interaction between the child and its environment. The present paper concentrates on pre- and perinatal factors and maternal psychopathology affecting mainly the early mother-child interaction and, in turn, child developmental outcome. PMID- 1454970 TI - Factor analysis of the Toronto Alexithymia Scale: elucidation of a polythetic construct. AB - The Toronto Alexithymia Scale (TAS) offers a reliable method to measure alexithymia, a personality construct describing individuals endorsing the inability to identify and report emotions, processing a minimal fantasy life, utilizing an analytic cognitive style, and tending to somatize. Utilizing four cohorts of both patients and controls, a three-factor solution emerged from a principal-components analysis utilizing a varimax rotation. The factors of inability to identify and report feelings, an analytic cognitive style, and paucity of fantasy life were independent and internally reliable. These data are reviewed in the context of previous research and offer three subscales for future investigations utilizing the Toronto Alexithymia Scale. PMID- 1454971 TI - Chronic idiopathic pain, mianserin and 'masked' depression. AB - In this study an attempt was made to provide controlled empirical evidence for the hypothesis that chronic idiopathic pain might be a specific form of 'masked depression'. For this purpose, chronic pain patients supposed to be suffering from a 'masked depression' were compared to patients with organic pain and coexistent depression, patients with only organic pain, and patients with only depression, in a double-blind placebo-controlled therapeutic trial with mianserin. Although mianserin appeared to have effective antidepressant properties in this study, no pain improvement was found in any of the three chronic pain groups. These results challenge the validity and clinical relevance of the 'masked depression' concept for chronic idiopathic pain. PMID- 1454972 TI - Strengthening the public health system. AB - Although the American public health system has made major contributions to life expectancy for residents of this country over the past century, the system now faces more complex health problems that require comprehensive approaches and increased capacity, particularly in local and State public health agencies. To strengthen the public health system, concerted action is needed to meet these five critical needs: First, the knowledge base of public health workers needs to be supplemented through on-the-job training and continuing education programs. To this end, self-study courses will be expanded, and a network of regional training centers will be established throughout the country. Second, communities need dynamic leadership from public health officials and their agencies. To enhance leadership skills and expand the leadership role of public health agencies, focused personal leadership development activities, including a Public Health Leadership Institute, and national conferences will provide a vision of the future role of public health agencies. Third, local and State public health agencies need access to data on the current health status of the people in their communities and guidance from the nation's public health experts. To improve access to information resources, state-of-the-art technologies will be deployed to create integrated information and communication systems linking all components of the public health system. Fourth, local and State agencies need disease prevention and health promotion plans that target problems and develop strategies and the capacity to address them. To provide communities with structured approaches to this process, planning tools have been developed and distributed, and technical assistance will be provided to local and State health agencies to involve each community in planning,priority setting, and constituency building.Finally, public health agencies need adequate resources to fund prevention programs. To improve the use of existing Federal support and enhance the availability of new community resources, grant programs will be modified, and innovative approaches to local resource enhancement will be developed and shared.Activities in these five key areas are designed to improve the infrastructure of the public health system and its capacity to carry out effectively the core functions of public health assessment, policy development, and assurance of the availability of the benefits of public health. If the nation is to achieve the health objectives for the year 2000, the public health system the individuals and institutions that, when working effectively together, promote and protect the health of the people-must be strengthened. PMID- 1454973 TI - The multidrug-resistant tuberculosis challenge to public health efforts to control tuberculosis. AB - After years of steady decline, there has been an unprecedented resurgence of tuberculosis (TB) in the United States and outbreaks of multidrug-resistant tuberculosis (MDR-TB). The authors assess the nature, epidemiology, and implications of MDR-TB; provide suggestions for preventing drug resistance among patients with drug-susceptible TB; and offer recommendations for managing patients with MDR-TB. They outline the National Action Plan to Combat MDR-TB. Close collaboration among medical practitioners and staff members of TB control programs is needed to ensure the most effective management of patients with TB and their contacts. This collaboration is one of the most important steps for successful control of MDR-TB. PMID- 1454975 TI - Czechoslovakia's changing health care system. AB - Before World War II, Czechoslovakia was among the most developed European countries with an excellent health care system. After the Communist coup d'etat in 1948, the country was forced to adapt its existing health care system to the Soviet model. It was planned and managed by the government, financed by general tax money, operated in a highly centralized, bureaucratic fashion, and provided service at no direct charge at the time of service. In recent years, the health care system had been deteriorating as the health of the people had also been declining. Life expectancy, infant mortality rates, and diseases of the circulatory system are higher than in Western European countries. In 1989, political changes occurred in Czechoslovakia that made health care reform possible. Now health services are being decentralized, and the ownership of hospitals is expected to be transferred to communities, municipalities, churches, charitable groups, or private entities. Almost all health leaders, including hospital directors and hospital department heads, have been replaced. Physicians will be paid according to the type and amount of work performed. Perhaps the most important reform is the establishment of an independent General Health Care Insurance Office financed directly by compulsory contributions from workers, employers, and government that will be able to negotiate with hospitals and physicians to determine payment for services. PMID- 1454974 TI - Social and cultural factors in the successful control of tuberculosis. AB - The burden of tuberculosis on the public health is staggering. Worldwide, annual incidence of new cases is estimated to be about 8 million. Almost 3 million deaths occur yearly. Early case identification and adherence to treatment regimens are the remaining barriers to successful control. In many nations, however, fewer than half those with active disease receive a diagnosis, and fewer than half those beginning treatment complete it. The twin problems of delay in seeking treatment and abandonment of a prescribed regimen derive from complex factors. People's confusion as to the implications of the tuberculosis symptoms, costs of transportation to clinic services, the social stigma that attaches to tuberculosis, the high cost of medication, organizational problems in providing adequate followup services, and patients' perception of clinic facilities as inhospitable all contribute to the complexity. Sociocultural factors are emphasized in this report because hitherto they have not been adequately explored. Salient among those sociocultural factors is the health culture of the patients. That is, the understanding and information people have from family, friends, and neighbors as to the nature of a health problem, its cause, and its implications. A knowledge of the health culture of their patients has become a critical tool if tuberculosis control programs are to be successful. Several anthropological procedures are recommended to help uncover the health culture of people served by tuberculosis clinics. PMID- 1454976 TI - Weighing costs and benefits of adequate prenatal care for 12,023 births in Missouri's Medicaid program, 1988. AB - Numerous studies have shown that the receipt of adequate prenatal care is associated with improvements in pregnancy outcome, particularly a reduction in the risk of low birth weight. Since medical costs for these low birth weight infants are several times higher than for normal birth weight infants, one would expect that medical costs for newborns would be lower for babies whose mothers have had adequate prenatal care than for those with inadequate prenatal care. Explored in this paper is whether the reduction in Medicaid costs for newborn and post-partum maternal care is greater than the increase in prenatal costs for a Medicaid population. The analysis used a file of 12,023 Missouri Medicaid records linked with the corresponding 1988 birth certificates. A modified version of the Kessner index was used to define the adequacy of prenatal care. Prenatal care costs were $233 higher for pregnancies with adequate prenatal care than for those in which prenatal care was inadequate. Newborn and post-partum costs starting within 60 days after the birth were $347 lower for the adequate prenatal care pregnancies, resulting in a savings of $1.49 for each extra $1 spent on prenatal care. Among the other factors studied in determining this benefit to cost ratio were global billing, Supplemental Food Program for Women, Infants, and Children (WIC), and participation in Medicaid under the expanded eligibility provisions that were effective in Missouri in 1988. PMID- 1454977 TI - Area-level predictors of use of prenatal care in diverse populations. AB - Patterns and predictors of the use of prenatal care in Hawaii were examined by census tract, taking into account summary measures of socioeconomic status, environmental conditions, and aggregated indicators of pregnancy-related risk characteristics of mothers. The objectives of the study were to identify those census tracts with high levels of inadequate use of prenatal care services; to develop a model, based on census tract characteristics, to explain observed geographic variations in the use of prenatal care services; and to identify for further investigation specific localities with unanticipated patterns of use. Data were drawn from 1980 census reports and vital statistics live birth files for the period 1979-87. Regression analysis was used to develop a model that was able to predict 61 percent of the census tract variation in the percentages of inadequate use of prenatal care services. Increased proportions of mothers of Japanese and other Asian-descent and of adults with more than high school education were associated with low levels of inadequate use of prenatal care services. Increased proportions of high parity-for-age risk and Samoan mothers were associated with higher levels of inadequate use. Census tract maps of actual and predicted percentages and studentized residual values were used to identify areas with high and low rates of inadequate use of prenatal care services. The area-level methods used are believed applicable to health care planning in other areas with ethnically or socioculturally diverse populations. PMID- 1454978 TI - Estimating the prevalence of mental disorders in U.S. adults from the Epidemiologic Catchment Area Survey. AB - The National Institute of Mental Health Epidemiologic Catchment Area Survey is a comprehensive, community-based survey of mental disorders and use of services by adults, ages 18 and older. Diagnoses are based on the criteria in the "Diagnostic and Statistical Manual of Mental Disorders," third edition, and were obtained in five communities in the United States through lay-interviewer administration of the National Institute of Mental Health Diagnostic Interview Schedule. Results from the survey provide the public health field with data on the prevalence and incidence of specific mental disorders in the community, unbiased by the treatment status of the sample. The population with disorders is estimated, and the survey findings that respond to some of the most common requests for information about the epidemiology of mental disorders in the United States are highlighted briefly. Based on the survey, it is estimated that one of every five persons in the United States suffers from a mental disorder in any 6-month period, and that one of every three persons suffers a disorder in his or her lifetime. Fewer than 20 percent of those with a recent mental disorder seek help for their problem, according to the survey. High rates of comorbid substance abuse and mental disorders were found, particularly among those who had sought treatment for their disorders. PMID- 1454979 TI - AIDS education for health care professionals in an organizational or systems context. AB - Traditionally, health education for practicing health professionals, as well as members of the public, focuses on the individual and relies on changing personal behavior. However, health care for persons with acquired immunodeficiency syndrome (AIDS), and members of their families, mainly is delivered within health and human services organizations. Providing AIDS education for health care professionals in an organizational or systems context shifts the focus from the individual to the group and from changing a person's behavior to offering health care professionals opportunities for interaction. In an organizational or systems approach, they can address patient care issues collectively, share interdisciplinary knowledge, identify problems of common concern, plan coordinated and integrated responses, and provide mutual support. A strategy for planning AIDS education is proposed for key administrators, supervisors, and care providers, who are the gatekeepers, opinion makers, and role models of organizations. Addressing organizational, community, and health care delivery system issues as part of an education program provides a forum for defining problems and a basis for uniting professionals and developing solutions. PMID- 1454980 TI - Needle sharing and participation in the Amsterdam Syringe Exchange program among HIV-seronegative injecting drug users. AB - To enhance the prevention of human immunodeficiency virus infection, factors related to regular participation in the Amsterdam Syringe Exchange and the borrowing of syringes were studied in 131 HIV-seronegative injecting drug users in a 1989-90 survey. A total of 29 percent of the users reported borrowing syringes, that is injecting drugs at least once in the past 4-6 months with a needle or syringe previously used by someone else. Users at increased risk of borrowing are previous borrowers, long term moderate-to-heavy alcohol users, current cocaine injectors, and drug users without permanent housing. Regular clients of the syringe exchange, when compared with other injecting drug users, were found more often to be frequent, long term injectors. They borrowed slightly less often than other users, but this was not statistically significant, even after controlling for frequency of injecting or other potential confounders. The results suggest that, 5 years after the start of the Amsterdam Syringe Exchange, drug use characteristics govern an individual injecting drug user's choice of exchanging or not exchanging syringes. The conclusion is that it seems more important to direct additional preventive measures at injecting drug users with an increased risk of borrowing rather than at users who do not participate in the syringe exchange or who do so irregularly. PMID- 1454981 TI - Breast cancer beliefs of women participating in a television-promoted mammography screening project. AB - A survey of breast cancer and breast cancer screening beliefs was mailed to a random sample of 1,000 women who contacted a telephone bank in response to a television-promoted, reduced-cost mammography project. Beliefs and demographics of women in the sample who subsequently completed a mammogram were compared with those who did not. No statistically significant differences were found between participants (persons who completed a mammogram) and nonparticipants with respect to age, race, marital status, income, or educational preparation. Groups also did not differ significantly in the series of beliefs examined. Factor analysis revealed respondents' most salient beliefs about breast cancer and early detection of breast cancer. Evidence is presented to suggest a need for enhanced efforts to recruit minority group women to participate in mammography screening. PMID- 1454982 TI - Seasonal variation in adolescent conceptions, induced abortions, and late initiation of prenatal care. AB - The monthly distribution of conceptions among adolescents and the proportion of adolescent pregnancies that are voluntarily terminated by induced abortion by month of conception are the objects of this study. Additionally, seasonal variations in the timing of initiation of prenatal care services by adolescents are investigated. Vital records files of single live births, fetal deaths, and induced terminations of pregnancy to residents in the State of South Carolina, 1979-86, were aggregated to estimate conceptions. There was a significant difference between adolescents and adults in the monthly distribution of conceptions. The peak month of adolescent conceptions coincided with the end of the school year. Pregnancies of adolescents occurring at this time further demonstrated later access of prenatal care services than conceptions occurring at other times of the year, most notably during the school term. These findings suggest that there is considerable opportunity for improving the availability of reproductive health care services for adolescents. The results specifically suggest the potential benefit of increasing adolescent pregnancy prevention efforts prior to high-risk events and increasing the availability of and access to health care and counseling services to adolescents during the school recess months of the summer. PMID- 1454983 TI - Sampler of findings from the 1986 national mortality followback survey on risk factors, disability, and health care. AB - The National Center for Health Statistics conducted a mortality followback survey of a national probability sample drawn from all deaths of U.S. adults in 1986 and an oversampling of deaths of persons with selected characteristics. Responses were received from the next of kin or other close relatives of 16,598 adult decedents (88.6 percent). Data were collected through a mail questionnaire, followed by telephone or personal interviews with nonrespondents. Data were also collected from the hospitals and other health care facilities used by the decedent in the last year of life. Illustrative results are presented on the four major subject areas studied: risk factors for premature death, disability and care in the last year of life, socioeconomic differentials, and the reliability of selected items reported on the death certificate. Researchers are encouraged to explore the data tape to pursue indepth epidemiologic studies. PMID- 1454985 TI - Survey of graduates of the Epidemic Intelligence Service as an approach to enhancing ethnic diversity among the nation's epidemiologists. AB - A survey was conducted to improve the recruitment, training, and retention of epidemiologists in the Epidemic Intelligence Service (EIS) Program of the Centers for Disease Control. The authors compared minority graduates of the program and nonminority graduates in several areas: reasons for application, degree of satisfaction, appropriateness of preparation for epidemiologic practice, and current professional activities. A closed-ended questionnaire was mailed to all 87 minority graduates from the program during the period 1970-88, and to 172 randomly selected nonminority graduates. Of 259 graduates surveyed, 234 or 90.3 percent returned the questionnaire--89.6 percent of minority graduates and 90.7 percent of nonminority graduates. Virtually all graduates were satisfied with their EIS experience (95.2 percent), have encouraged others to apply (96.1 percent), and are the most frequent sources of initial contact of prospective officers (38.2 percent). Most EIS graduates (71.2 percent) were still working in epidemiology. Compared with the nonminority graduates, the minority graduates were more likely to be women and to be single. Minority graduates were less likely than non minorities to hold academic appointments (44.2 percent versus 60.0 percent) and less likely to work in academic settings as their primary job (11.5 percent versus 18.7 percent). At the same time, minority graduates were more likely to have learned of the EIS Program from academic advisors (32.1 percent versus 19.4 percent). Graduates express high levels of satisfaction with the EIS Program and continue to practice epidemiology following graduation. Few differences between the minority and nonminority graduates were found. Because fewer minority graduates are in academic settings to serve as mentors or role models, alternative recruitment methods must be developed to sustain a high level of interest among minority groups in the EIS Program. PMID- 1454984 TI - Vitamin supplement use and its correlates among elderly Japanese men residing on Oahu, HI. AB - Use of vitamin supplements and the association with personal characteristics were investigated among 4,654 American men of Japanese ancestry in Hawaii. A total of 58 percent of the subjects who were ages 68 to 90 took vitamin supplements. Among supplement users, multivitamins were most commonly used (77 percent), followed by vitamin C (53 percent), E (43 percent), and A (10 percent). Ninety-two percent of users took at least seven pills per week when all types of pills were combined. Vitamin supplement users were more educated, more physically active, more likely to be married, and less obese than nonusers. They also slept less, smoked less, and drank less alcohol and caffeine. They took more analgesics and stomach medication and had fewer days of hospitalization in the previous 10 years compared with nonusers. Except for physical activity, use of stomach medicines, and hospitalization, the other characteristics were also positively correlated with the amount of vitamin pill intake. These findings indicate that vitamin supplement users have different health patterns compared with nonusers. PMID- 1454986 TI - An evaluation of the Vermont worksite smoking law. AB - In view of the fact that the impact of statewide smoking laws on private worksite policies and the smoking behavior of employees has not been evaluated, two cross sectional surveys were performed in Vermont to measure compliance with such a law: a random-digit telephone survey of employees and a subsequent mail survey of their employers. Employers were not aware that one of their employees had been surveyed. Roughly half (56 percent) of the employees and 66.5 percent of their employers described policies that are in compliance. Among all employers who described policies in compliance with the law, 68.1 percent of their employees also described compliant policies. Among all employees who described non compliant policies, 48.8 percent had employers who described compliant policies. Overall, employees and employers agreed on how their policies stood with respect to compliance in 67.6 percent of cases. The prevalence and amount of smoking at work declined after the institution of the law but so did the prevalence and amount of smoking at home. Changes toward more restrictive policies were associated with reductions in cigarette consumption at work, but not with quitting. The study suggests that a large fraction of worksite smoking policies may not comply with a statewide worksite smoking law. The proportion of companies complying with such a law may be overestimated if information on compliance is obtained only from employers. PMID- 1454987 TI - Group counseling at STD clinics to promote use of condoms. AB - An intervention was developed to promote safer sex and condom use among patients seeking treatment for sexually transmitted disease (STD) at a public health STD clinic in Los Angeles, CA. The intervention consisted of a short group discussion on condom use, a presentation of a videotape portraying condom use as socially acceptable behavior, and a role-playing session concerning negotiating the use of a condom with one's sex partner. The study group was 551 persons who visited the clinic in 1988. Medical records of 426 (77 percent) were located and reviewed 7 to 9 months later. Among those, 220 had participated in the intervention and 206 were control subjects who had not participated in the intervention. The rates at which patients reacquired STD after treatment and after the intervention were compared between the intervention group and the control group. Men who participated in the intervention subsequently showed a lower rate of STD reinfection than those who did not. There was no evidence that the intervention reduced reinfection among women. The strongest predictor of reinfection was found to be a history of STD infection prior to the infection that was being treated at the time of the intervention. The results show that group interventions directed to STD patients can be effective in reducing STD reinfection among men. PMID- 1454988 TI - Mothers' motivations to participate in a pregnancy health survey. AB - An important question in interpreting epidemiologic data is why some persons agree to participate in a health survey while others do not. Information about why people agree to interview or answer a questionnaire could help researchers to devise procedures for a health survey and to chose information to be communicated in the interview or questionnaire so as to increase subjects' participation. The authors interviewed 180 mothers who gave birth to a child with a birth defect and 198 mothers whose children were born without a birth defect. The interviews were part of two case-control studies to determine risk factors for selected birth defects. In the course of the interviews, each mother was asked why she agreed to be interviewed, and whether anything about the survey procedures that were followed could be improved. Among both the case mothers and the control mothers the most common reason for agreeing to be interviewed was humanitarian, expressed as "to help others" or "to prevent what happened to my baby from happening to babies in the future." Case mothers, more frequently than control mothers, gave as their reason for participating either to help themselves, their child, their family, or to further scientific understanding. Emphasizing these as benefits of participation to those who are survey subjects at the time of the initial contact could increase the proportion who agree to respond. PMID- 1454989 TI - NIDA campaign spotlights drugs-alcohol-HIV link. PMID- 1454990 TI - U.S. leads in funding AIDS prevention projects in Third World countries. PMID- 1454991 TI - Environment, behavior, and injuries. PMID- 1454992 TI - Are physicians "primed" by nurses? PMID- 1454993 TI - Hospital records missing: "spoilation of evidence". Case in point: DeLaughter v. Lawrence Cty. Hosp. (601 So. 2d 818--MS [1992]). PMID- 1454994 TI - Legal case briefs for nurses. NM: nurse sues surgeon for assault & battery with bone chisel; IL: simultaneous removal of catheter and tape: stands of care issue. PMID- 1454995 TI - Is your patient complaining of "pain" or "burning"? Case in point: McLain v. Glenwood Reg. Medical Center (601 S.E. 2d 240--LA [1992]). PMID- 1454996 TI - Effect of disease on glomerular proteinases. AB - Up to now, little is known about the self-perpetuating mechanism leading to terminal renal failure in chronic renal disease. The common pathological feature of progressive renal insufficiency is focal and segmental glomerulosclerosis. The experimental counterpart of this process is represented for instance by the models of streptozotocin diabetes, Adriamycin nephropathy and Goldblatt hypertension. In fact, the main initiating hallmark of glomerulosclerosis is an accumulation of glomerular proteins, whose balance is apparently influenced by the activity of glomerular proteinases. In isolated glomeruli of kidneys from the experimental animals, the total proteinase activity was assayed with the unspecific but sensitive azocasein assay. In fact, the activity was significantly reduced in all experimental models at acid and neutral pH when relating enzyme activity to the glomerular protein and DNA content. We believe, that our data of reduced glomerular proteinase activity in the animal models of glomerulosclerosis represent perhaps a new additional common pathogenetic mechanism. The glomerular protein accumulation could be a result of a synergistical interaction between hemodynamic factors and biochemical ones; the latter, we suggest to be a decrease of glomerular proteinase activity. PMID- 1454997 TI - [Immunopathogenesis of glomerulonephritis--new data on the clinical and experimental studies]. PMID- 1454998 TI - [Immunopathogenesis of IgA nephropathy--new data based on the clinical and experimental studies]. PMID- 1454999 TI - [Pathophysiology of nephrotic proteinuria and the principles of the symptomatic treatment]. PMID- 1455000 TI - [Late results and prognosis in glomerulonephritis. I. General remarks]. PMID- 1455001 TI - [Late results and prognosis in glomerulonephritis. II. Prognosis in specific forms of glomerulopathies]. PMID- 1455002 TI - [Erythropoietin in 1991--pathophysiological and therapeutic aspects]. PMID- 1455003 TI - Response to EPO therapy. PMID- 1455004 TI - Subcutaneous erythropoietin in the treatment of renal anaemia. AB - Erythropoietin was applied subcutaneously to 49 patients, 41 have been treated by hemodialysis, 3 by continuous ambulatory peritoneal-dialysis, 5 had chronic progressive renal failure. Mean initial dose of erythropoietin was 139.4 U/kg/week and maintenance dose 115.9 U/kg/week. In 43% of patients serum ferritin was decreasing during treatment, and in 20% it was low before the commencing of the treatment. During erythropoietin therapy vitamin B12 was decreasing in 22% of the patients, and the substitution was necessary in 18%. Only in 1 patient it was necessary to substitute also folic acid. There were no nonresponders among erythropoietin treated patients. Elevation of blood pressure was observed in half of the patients, hypertensive encephalopathy in 1, and thrombosis of arterio venous fistula in 3. PMID- 1455005 TI - Recombinant human erythropoietin for anaemia associated with chronic renal failure in predialysis patients. PMID- 1455006 TI - Influence of long-term erythropoietin therapy on endocrine abnormalities in haemodialyzed patients. AB - Endocrine abnormalities in patients with chronic renal failure are well documented. The present study aimed to assess the influence of long-term erythropoietin (EPO) therapy on endocrine abnormalities in haemodialyzed patients. Two groups of haemodialyzed patients, each of which comprised 17 subjects, were examined. The first one treated by EPO (EPO group) while the second one did not receive this hormone (NO-EPO group). A complete biochemical and hormonal check-up was performed before and at the 3, 6, 9 and 12 months of the study period. Normal values for the estimated parameters were obtained in appropriately selected sex and age-matched healthy subjects. After EPO therapy an increase of the haematocrit value from 21.8 +/- 0.9% to 32.6 +/- 0.9% was observed which was accompanied by a significant decline of plasma ferritin and saturation of transferrin. In patients of the NO-EPO group a significant although less marked rise of the haematocrit value (21.4 +/- 0.4% to 24.2 +/- 0.6%) was also noticed. EPO therapy did not change electrolytes (Na, K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose and alkaline phosphatase plasma levels as well as plasma concentrations of calcium related hormones (PTH, calcitonin, 1.25(OH)2D3) and vasopressin (AVP). EPO treatment induced a significant decline of somatotropin (HGH), prolactin (PRO), follitropin (FSH), lutropin (LH), ACTH, cortisol, plasma renin activity, aldosterone, insulin (IRI), glucagon (IR-G), pancreatic polypeptide (PP) and gastrin plasma levels and an increase of plasma estradiol, testosterone and atrial natriuretic peptide (ANP). These EPO induced endocrine alterations were restricted mostly to the first 6 months of EPO administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455007 TI - [Effect of recombinant human erythropoietin (rHu-EPO) on anemia and selected biochemical parameters in patients in the pre-dialysis period]. AB - The effect of recombinant human erythropoietin (rHu-EPO) on anaemia and some biochemical parameters was investigated in 7 predialysis patients. A statistically significant increase in erythrocyte, haematocrit and haemoglobin levels was observed after 3 weeks of treatment and such changes were constant during the 6 month maintenance therapy. The mean urea and creatinine levels were comparable during the tested period in 4 of the studied patients. The other 3 patients did not completed the planed period and started the dialytic therapy because of progression of renal insufficiency. The latter group had more advanced renal failure and higher blood pressure prior to rHu-EPO treatment as compared with the patients who completed the study. PMID- 1455008 TI - [Effect of recombinant human erythropoietin--rHu-EPO on the metabolism of children treated by long-term hemodialysis]. AB - Recombinant human erythropoietin (EPO) was administered to 12 children with terminal renal failure aged 8-17 years subjected to hemodialysis for a mean period of 16 (S.D. = 19.7) month prior to EPO utilisation. The hormone was administered thrice weekly at an intravenous dose of 25-75 u/kg until Hb value of 100 g/l was obtained, and subsequently at maintenance doses for mean period of 7 (S.D. = 4.0) month. The urea kinetic modeling (UKM) algorithms allowed to compute protein catabolic rate (pcr) for each patient in modeling sessions performed once a month. The analysis included the effect of EPO upon: 1. peripheral whole blood count; 2. individual UKM parameters; 3. selected lab data describing the metabolic status of the patient (predialysis potassium, phosphorus, creatinine, total blood protein and albumin--and iron levels), in three randomized groups according to the value of pcr. Group I presented pcr less than 1.0 g protein/kg/day typical for malnutrition; group II--pcr = 1.0-1.4 g protein/kg/day -with appropriate protein catabolism; group III--pcr greater than 1.4 g protein/kg/day--hypercatabolic. The results from 188 pre-EPO modeling sessions and 78 sessions in the course of EPO treatment were compared. All the three groups revealed statistically significant increased Hb, Ht and erythrocyte count after EPO administration, which also resulted an increase of protein catabolism what is manifested in a decrease in the number of sessions by 26.1% in Group I and a corresponding increase by 13.5% and 12.6% in Groups II and III, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455009 TI - Interactions among emergent relations during equivalence class formation. AB - The interactions among symmetry, transitivity, and equivalence tests during the formation of 3-member equivalence classes were studied with 14 college students. After training AB and BC, a test with BA, CB, AC, and CA was conducted concurrently. Failure led to serial testing with probes for CA equivalence, BA symmetry, CA equivalence, CB symmetry, CA equivalence, AC transitivity, and CA equivalence. For five subjects, equivalence tests were passed immediately once BA and CB symmetry as well as AC transitivity had been induced. Thus, symmetry and transitivity were precursors for successful performance on equivalence tests. The conjoint function of symmetry and transitivity was assessed with the equivalence probes. As the equivalence probes were passed immediately, the presence of symmetry alone and transitivity alone were sufficient for their conjoint function without additional intervention. For different subjects, transitivity alone and symmetry were induced either directly with BA, CB, or AC probes or indirectly with equivalence probes. Equivalence probes can also induce various combinations of symmetry and transitivity. Thus, different subjects formed classes in various patterns at different rates. PMID- 1455010 TI - Increased responding to female stimuli as a result of sexual experience: tests of mechanisms of learning. AB - Sexual experience increases the response of males to stimuli provided by female conspecifics in a variety of species. The mechanisms of learning involved in this type of phenomenon were explored in two experiments with Japanese quail. The results indicated that instrumental conditioning with copulatory opportunity is not necessary for the acquisition of responding to female cues, and responding is not facilitated by learning about the location of the female. However, the response of males to female stimuli (as well as to arbitrary stimuli associated with access to a female) was enhanced by the presence of sexually conditioned contextual cues. Substantial levels of responding also occurred to female stimuli in a context where the subjects never encountered a female quail before. This latter outcome is consistent with the possibility that stimuli from a female become directly associated with sexual reinforcement during the course of sexual experience. Similar forms of learning may be involved in the effects of sexual experience on the response of mammalian species to female odours. PMID- 1455011 TI - Effects of an infusion of morphine into the accumbens nucleus upon acquisition of hypoalgesic and fear responses in rats exposed to a heart stressor. AB - Four experiments examined the effects of an infusion of morphine into the accumbens nucleus upon the aversive conditioning that can occur in rats exposed to the heated floor of a hot-plate apparatus. An infusion of morphine into the accumbens nucleus but not into the caudoputamen or into the prefrontal cortex impaired the acquisition of a conditioned hypoalgesic (Experiment 1) and fear (Experiment 4) response. This impairment was dose-dependent (Experiment 2) and mediated by opioid receptors in the accumbens nucleus, because it was removed by a systemic (Experiment 3a) or by an accumbal (Experiment 3b) infusion of naloxone. The results were attributed to an antagonism between the reinforcement process for aversive conditioning and the appetitive properties of an accumbal infusion of morphine. PMID- 1455012 TI - Conditioned tolerance to morphine hypoalgesia: compensatory hyperalgesia in the experimental group or conditioned hypoalgesia in the control group? AB - Five experiments used rats to examine the role of noxious stimulation in the development of contextually controlled morphine hypoalgesic tolerance and in the mediation of this tolerance by an associated hyperalgesic response. There was evidence for contextually controlled tolerance to morphine's hypoalgesic effects and an associated hyperalgesic response in rats injected with morphine and trained with noxious stimulation, but not in rats repeatedly exposed to morphine in the absence of that stimulation (Experiments 1 and 5). Latent inhibition (Experiment 2) and extinction (Experiment 3) of tolerance also depended upon pairing drug-related cues with noxious stimulation. The level of sensitivity reactivity to noxious stimulation in morphine-tolerant rats tested with the drug was related to the intensity of the noxious stimulation that had been paired with the test context (Experiment 4). The results were interpreted to mean that some of the evidence for a Pavlovian involvement in tolerance development can be explained in terms of morphine's interference with the acquisition, but not with the expression of the hypoalgesic response otherwise acquired by cues paired with noxious stimulation. PMID- 1455013 TI - The purification and sequence analysis of an avian neuromedin U. AB - In this study we have purified an avian homologue of neuromedin U from the chicken. Each step of the purification process was followed by a specific radioimmunoassay developed using porcine neuromedin U. Microsequence analysis characterised the peptide to be 25 amino acid residues long with the following sequence: Y-K-V-D-E-D-L-Q-G-A-G-G-I-Q-S-R-G-Y-F-F-F-R-P-R-N. Chicken neuromedin U has marked sequence similarity with the porcine peptide at its bioactive C terminal region. Our findings demonstrate that the amino acid sequence of neuromedin U is markedly conserved in species which have diverged millions of years ago in evolutionary terms. PMID- 1455014 TI - The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels. AB - Endothelium-independent vasoconstrictor responses in isolated segments of human internal thoracic artery (ITA) and saphenous vein (SV) were used as a bioassay system for the vasoinhibitory activity of bovine chromogranin A (CGA). Preincubation with vasostatin (0.8 micrograms/ml), containing the N-terminal domain of CGA, (CGA1-76, CGA1-113 and CGA1-143ff), inhibited the contractile responses evoked by 80 mM K+, 2.6 microM noradrenaline (NA), or 65 nM endothelin 1 (ET-1) in Ca(2+)-free solution in SV but not in ITA. The results demonstrate a vasoinhibitory activity in vasostatin and show that there is a marked difference between the arterial and venous segments in the Ca2+ independent component of the inhibitory response. A vascular role for the N-terminal domain of CGA is indicated, presumably by inhibiting Ca2+ release from intracellular stores in the human vein but not the artery. PMID- 1455015 TI - [Clinico-radiologic correlations in the adult respiratory distress syndrome]. PMID- 1455016 TI - [Pneumothorax in multiple trauma. Radiologic and CT study]. AB - This study was aimed at evaluating the necessity to perform chest Computerized Tomography (CT) in multiple traumatized patients to diagnose pleuropulmonary lesions and, particularly, pneumothorax: the correct identification of this condition, although minimal, is important especially in prevision of long anesthesias and/or positive end-expiratory pressure (PEEP) therapy. This assisted respiratory technique improves arterial oxygenation but causes a barotrauma which may cause some complications; particularly, a small undetected pneumothorax can suddenly increase so as to cause pulmonary collapse with sometimes dramatic symptoms. Chest X-ray films and CT scans, performed in rapid succession on patient's admission in Emergency Ward, were compared in 21 subjects. CT is indispensable in case of severe chest parietal lesions which can mask the radiological evidence of pulmonary or pleural conditions, as it occurred in 3 of our cases. Moreover, CT resulted more reliable than chest X-rays (18 versus 10 correct diagnoses) especially in the detection of small antero-inferior pneumothorax flaps, in which direct radiological signs cannot be identified, in default of radio-geometrical assumptions. Indirect radiological signs of pneumothorax must be recognized but critically considered in order to avoid over staging. PMID- 1455017 TI - [Radiologic characteristics of the thorax during therapy with interleukin-2]. AB - Interleukin-2 is a glycoprotein physiologically produced by human lymphocytes which is capable of mediating some still unknown immunologic reactions. In vitro, interleukin-2 was seen to induce a lytic reaction against tumor cells through the activation of a cytolytic system of natural killer cells. If administered to man in heavy doses, it causes a clinical response in the treatment of metastases from melanoma and renal cell carcinoma in 20-40% of cases. However, the clinical use of the drug, in therapeutic doses, is prevented by the occurrence of several side effects, the major one being increased permeability of alveolar vessels with capillary leak and interstitial pulmonary edema (Vascular Leak Syndrome in the English literature). Thus, this work was aimed at evaluating chest radiographs during interleukin-2 treatment to detect, in the pulmonary district, the early stages of the vascular leak syndrome--i.e., pulmonary edema, pleural and pericardial effusions. Forty-three patients had been treated for metastases from renal cell carcinoma and melanoma November 1989 through September 1991: standard chest radiographs demonstrated 26 cases (60%) of pulmonary edema, 14 cases (32%) of bilateral pleural effusions and 12 cases (27%) of pericardial effusions. Daily chest films of the patients undergoing interleukin-2 therapy allowed the early stage of the vascular leak syndrome to be depicted, thus enabling the physician to use the highest tolerated doses and eventually to stop infusion before marked respiratory distress develops. PMID- 1455018 TI - [Bronchogenic carcinoma staging: comparison of magnetic resonance/computerized tomography]. AB - The staging of bronchogenic carcinoma is an important factor to select the appropriate treatment. Indeed, the definition of locoregional spread and of hilar and mediastinal node involvement is essential for both correct preoperative assessment and prognostic evaluation of bronchogenic carcinoma. CT and MR imaging are the methods of choice in the evaluation of T and N, even though other techniques--e.g., US and nuclear medicine--can also provide valuable diagnostic information. The authors examined 50 patients with primary bronchogenic carcinoma by means of plain radiographs, CT and MR of the chest. MR and CT findings were compared with surgical results on the basis of TNM classification. In the evaluation of T, sensitivity and specificity were 66% and 88.6%, respectively, for CT and 76% and 92% for MR imaging. No statistically significant differences were found between the two imaging methods (p = 0.19). In the evaluation of N, sensitivity and specificity were 56% and 78%, respectively, for CT and 76% and 88% for MR imaging. A statistically significant difference was found between MR and CT accuracy rates (p = 0.934). CT and MR results were in disagreement especially in the evaluation of hilar lymph nodes. To date, MR imaging cannot be considered a substitute for or a routine adjunct to CT in the staging of bronchogenic carcinoma due to its poor spatial resolution, to the presence of artifacts (especially with high-intensity fields), its cost and limited availability. However, in the evaluation of specific anatomical regions--e.g., the pulmonary apex and the peridiaphragmatic region--MR can provide more diagnostic information than CT thanks to its multiplanarity and better contrast resolution. PMID- 1455019 TI - [Echography in the diagnosis of patellar instability]. AB - The authors examined with US the femoropatellar relationship on the lateral aspect of the knee in 20 patients (40 knees) with clinical symptoms of patellar instability; 20 healthy subjects (40 knees) were also studied as a control group. US examinations were performed with a 7.5 MHz probe, positioned perpendicular to the lateral aspect of the knee on a plane passing through femoral epicondyle and the middle third of patella. The results were compared with those obtained by means of conventional radiologic techniques and CT. US was useful to show lateral shift of patella, also in fully extended or in 30 degrees flexed knees-i.e., in the cases where conventional radiology meets with the greatest difficulties. CT is much more accurate but certainly more expensive and often not available. With progressive flexion of the knee, the gradual medialization of patella can be followed, which will be complete at a variable degree of flexion according to the initial lateral shift. PMID- 1455020 TI - [Role of computerized tomography in the densitometric assessment of lithiasis of the gallbladder]. AB - Radiolucent gallstones frequently contain significant calcium deposits. Their detection is important to select the patients to submit to medical gallstone dissolution. Since CT facilitates the identification of calcifications undetected at conventional radiologic procedures, 60 patients were studied with CT. All of them had US confirmation of cholelithiasis and in the whole of cases an X-ray examination of the right upper abdominal quadrant was performed (for the identification of radiopaque stones), together with oral cholecystography (to evaluate gallbladder function). CT attenuation values of the stones were measured and the patients subsequently divided into 2 groups; the threshold value was 50 HU: below it, the stones were considered hypo- or isodense (group I); above it, they were considered hyperdense (group II). Later on, 28 patients (14 from group I and 14 from group II) were selected for chemical dissolution with ursodeoxycholic acid over a 1-year period. US examinations were performed at 6 and 12 months. Seventy per cent of the patients in group I responded to treatment (50% with complete stone dissolution and 20% with partial dissolution), whereas no patient in group II had complete dissolution and only 30% had partial response. PMID- 1455021 TI - [Liver transplantation: diagnostic imaging in the preoperative assessment]. AB - The correct selection of patients for liver transplantation, which is essential for surgical success, requires thorough radiological evaluation. The authors present their experience on 94 pretransplant adult patients that underwent a total of 251 diagnostic exams (Doppler US, CT, angiography and cholangiography) and interventional radiology maneuvers (biopsy, chemoembolization, biliary drainage). Three sclerosing cholangitis, 3 Budd-Chiari syndromes and 20 hepatocellular carcinomas in cirrhotic patients were identified; venous collaterals were present in 62.7% of the cases, 12.8%, of which had important spontaneous porto-systemic shunts; 6 patients had portal thrombosis; 20 arterial variations were found. Interventional maneuvers were useful and free of complications. US, CT and angiographic findings of each patient were compared. Integrating informations from different exams allowed a significant increase in the accuracy of diagnostic conclusions. Thanks to interventional maneuvers 5 patients could be selected for transplantation (hepatic arterial lipiodolization stopped the growth of 4 hepatic neoplasms; 2 infected fluid collections were sterilized by percutaneous US-guided drainage and topic therapy. PMID- 1455023 TI - [Ultrasound-guided biopsy of small abdominal lesions. Methodology implications]. AB - In the present study the diagnostic accuracy of US-guided fine-needle biopsy was evaluated in a series of 219 abdominal lesions < or = 3 cm in diameter (21 between 0.6 and 1 cm; 83 between 1.1 and 2 cm; 115 between 2.1 and 3 cm). One hundred-eighty-three of them were located in the liver and 36 in other abdominal organs (pancreas, 10, adrenals 9, lymphnodes 9, kidney 5, spleen 3). Biopsies were performed with "free-hand" technique using up-to-date ultrasound equipment. The demonstration of the correct location of the needle tip at the time of sampling was looked for with great care. The sensitivity rate was 93%, with a progressive improvement with the increase of the lesion size (83.3% between 0.6 and 1 cm; 91.1% between 1.1 and 2 cm; 95.4% between 2.1 and 3 cm). The specificity rate was 100%. In 207 cases in which the location of the needle tip was clearly demonstrated, the sensitivity reached 97.3% and the negative predictive value 93%. No noteworthy complications were observed. Ultrasonography is a highly reliable guidance modality also in biopsies performed on small abdominal lesions; if the correct location of the needle tip is clearly shown, even a diagnosis of benignity can be confidently made. PMID- 1455022 TI - [Liver transplantation: role of the radiologic methods in the postoperative period]. AB - Some complications of liver transplantation appear as aspecific clinical and blood test abnormalities; others--e.g., hepatic artery thrombosis in the immediate postoperative period and stenosis of the biliary anastomosis before T tube removal--require early diagnosis. These considerations justify the need of frequent radiologic examination in both the complicated course and the follow-up. The authors report their experience in 59 adult patients submitted to liver transplantation for irreversible liver disease in advanced stage (49 with cirrhosis, 10 with HCC; 5 with cholestatic hepatopathy; 3 with fulminant hepatitis; 1 with Budd-Chiari syndrome; 1 with metastatic APUDoma). Two hundred and sixty-three radiological examinations were performed (Doppler US, CT, angiography and cholangiography) which showed numerous early and delayed complications: 13 of them were treated with interventional radiology maneuvers (US-or CT-guided percutaneous drainage of fluid collections, biliary drainage, bilioplasty, arterial transcatheter embolization). Our results demonstrate that diagnostic and operative radiology are essential for the success of liver transplantation; integrated imaging is particularly important in the diagnosis of complications, while interventional radiology techniques can be usefully employed in their treatment. PMID- 1455024 TI - [Role of endovesical echography in the assessment of bladder neoplasms]. AB - The correct assessment of T (depth of infiltration of bladder wall by cancer) is relevant to plan therapy. In fact, besides staging the local lesion, this can predict pelvic and lumboaortic lymphnode involvement (N parameter) statistically. At the INRCA Hospital in Florence, from January 1987 to December 1989, transurethral US was performed on 66 patients affected with bladder carcinomas, in order to assess the value of this diagnostic method; in all patients pathologic staging on surgical specimens from TUR (63 cases) and cystectomy (3 cases) was performed. Follow-up lasted 24 months at least. When comparing US staging (according to Holm classification) to postoperative histopathologic findings, our results showed that US tends to overstage the lesions, while no understaged tumors were seen in our series. Diagnostic accuracy was 70%. It must be pointed out that TRUS demonstrated hidden submucosal tumors in two patients previously treated with intravesical chemotherapy. Retrospectively, we were able to detect causes of error in cancer staging in some cases--i.e., large carcinomas, calcifications on tumors, radiotherapy scars, bladder wall inflammation due to intravesical BCG therapy. Moreover, some lesions which appeared to have been overstaged with TRUS and which had been treated according to histopathologic findings from TUR exhibited recurrence or disease progression. This was probably due to incomplete TUR and to the presence of residual tumor in the bladder wall. PMID- 1455025 TI - [Radiodiagnosis of ureteral and bladder hernia. A further case contribution]. AB - The radiologic features of ureteral and bladder hernias are poorly known. These hernias can be located in 5 compartments, being extremely rare in 2 of them--the chest and lumbar sectors, where only 2 cases are reported in literature. In the other 3 compartments--i.e., ischiatic, crural and inguinal sectors--bladder and ureteral hernias are less uncommon findings. Over a relatively short period of time, 5 bladder hernias were observed--3 ischiatic, 1 inguino-scrotal and 1 crural cases--and 1 double ureteral hernia, which was inguinal on the right-hand side and ischiatic on the left-hand side. Thus, we reviewed the main urographic and cystographic signs on the basis of a previous report by one of us. In discussing the new cases, we emphasize the importance of a few typical diagnostic signs, which follow: asymmetry and anomalous location of herniated organs, ureter protrusion beyond the pelvic bones outline, the presence of ureteral spiral ("curlicue sign"), and bladder walls indentation. PMID- 1455026 TI - [Seminal vesicles: echographic findings in 244 subjects. Evaluation of anatomic data and correlations with pathologic prostatic-vesicular parameters]. AB - Over a 2-year period (1989-90), about 400 cases were examined (out of nearly 2,500 US examinations of the prostate), 244 of which had subsequent bioptic, surgical or autoptic confirmation. This paper reports the anatomic, clinical and pathologic data relative to the seminal vesicles of 244 subjects who underwent transrectal US of the prostate for different clinical indications. Our biometric values were slightly different from those reported in literature, the latter being based on autoptic findings. Agenesis and monolateral ectopia were confirmed to be extremely rare: 4 cases only (1.6%) in our series. A typical finding was the nearly perfect symmetry; in size and structure, of the two seminal vesicles in the same subject; as a matter of fact, a loco-regional pathologic condition was detected in all the patients (14) with asymmetry. A hundred per cent agreement was observed between the US patterns of the seminal vesicles and the prostatic patterns in case of acute/subacute prostatic inflammation involving also the 2 glands: this parameter can be used to follow the clinical course of the inflammatory process. PMID- 1455027 TI - [Computerized tomography follow-up after percutaneous renal lithotripsy]. AB - Even though extracorporeal shock wave lithotripsy (ESWL) is nowadays considered the treatment of choice for the majority of upper urinary tract calculi, percutaneous stone removal will continue to be an alternative treatment method in selected cases. Therefore, percutaneous techniques must not be forgotten by the interventional radiologist. In order to assess the effects and the potential damage caused by this interventional procedure to kidney and perirenal tissues, CT was performed on 20 patients before and after percutaneous nephrolithotripsy. In the cases where no complications occurred during the maneuver, post nephrolithotripsy scans demonstrated low incidence of significant renal abnormalities. Thickening of pararenal fascia (8 patients) and irregular renal outline (10 patients) were our most frequent findings. In 5 patients we found edema of the pyelo-ureteral junction, in 3 thickening of the bridging perinephric septa and retained stone fragments, in 2 perirenal hematomas, in one a subcapsular fluid collection. Urinoma with pelvic laceration was demonstrated in the only patient in whom the maneuver presented marked technical problems. On the basis of this series of pre- and post-nephrolithotripsy CT scans of treated kidneys, the authors conclude that this percutaneous technique is quite atraumatic. PMID- 1455028 TI - [Results of conservative treatment of stage I-II carcinoma of the breast. Analysis of 311 patients]. AB - From January 1984 through December 1990, 311 patients affected with breast cancer were treated with quadrantectomy plus lymphadenectomy and radiation therapy (QUART) at the Umberto I Hospital in Mestre, Italy. The patients with positive nodes (N+) were treated with adjuvant chemotherapy (CMF) or hormonotherapy (Tamoxifen) according to pausal status. Most patients were in the 5th, 6th and 7th decades of life; 60.5% of them were over 50. Staging was always performed according to TNM classification (UICC criteria) and demonstrated mostly stage-I lesions (66.9%). Overall and disease-free (NED) survival rates were 95%; mean survival rates were 7.47 (+/- 0.138) and 7.22 (+/- 0.164) years, respectively. Ten patients died (5 from breast cancer); 6 local relapses were observed and 8 metastases. Metastases were seen mostly in patients with breast cancer in the internal quadrants (QI) N0, with no statistically significant differences relative to the other groups. This is probably due to the existence of an axillary pN0 and parasternal N+ group of patients, who receive insufficient treatment. PMID- 1455029 TI - [Radon levels in interiors in Valtellina, on the Angera hills and in the high valley of the Cervo river]. AB - The results are reported of an investigation carried out from 1988 to 1990 in many houses in various sites in Lombardy and Piedmont. Measurements were actually carried out in Valtellina, in Angera--on the Lombard side of lake Maggiore--and in the high valley of the river Cervo, north of Biella. The patterns of radon immission in houses due to buildings materials and also to soil emissions are described. Average values of radon levels were obtained using track-etch detectors, whereas fluctuations were recorded daily with a unit capable of detecting alpha particles in real time. Some of the values obtained in 28 Valtellina towns were quite high--e.g., about 1,000 Bq/m3 in towns along the Insubrica fault. The area around Bormio and the Masino valley did not exhibit high radioactivity levels. A total number of nearly 100 houses were investigated in Angera; the highest radon concentrations were observed in cellars and especially in the areas where fractures are bigger and more diffuse. One particular house was accurately examined with real-time analysis of radon fluctuations. Four small towns in the pluton area were investigated in the valley of the river Cervo. In this instance, values were generally high (mean concentration: 842 Bq/m3); the highest concentrations were found in cellars and in ground-floor rooms. PMID- 1455030 TI - [Teleradiography for diagnosis in emergency care. A clinical experience]. AB - This work was aimed at evaluating the role of teleradiology in a diagnostic emergency room. Over a 6-month period (September 1991-February 1992), 2,000 films made in the emergency room were transmitted to a resident radiologist 1 kilometer away: each examination included patient's data (sex, age, site of trauma, etc.) which were sent by the admitting physician. A teleradiology system (Lumiscan 100 AT&T and Philips) was used. Films were digitized on a 1024 x 1024 x 8-bit image matrix and then transmitted over a dedicated standard phone line to the Department of Radiology. The autograph report was sent by fax to the emergency room. Four radiologists, of varying experience, independently reviewed a sample of 179 digitized radiographs and, 30 days later, the original films on a conventional light-box. The results appear to be encouraging because no significant differences were observed in the performance of any of the radiologists. Good video/films agreement was obtained, together with high sensitivity and specificity. A good result was the relatively small number (0.4% of all examined cases) of false negatives diagnosed on faxed films relative to the actual clinical diagnosis. PMID- 1455031 TI - [Conventional radiology, digital radiology with photostimulable phosphor, laser digitalization of thoracic radiographic films at the bedside. A comparative study]. AB - The bedside chest images obtained with conventional radiology and with "on line" and "off line" digital modalities were compared to evaluate the respective capabilities in visualizing chest anatomical structures. Seventy patients were submitted to bedside chest examinations with a portable unit; both a conventional film and a digital system (PCR Graphics 1, Philips) with photostimulable phosphor imaging plate were fitted in the radiographic cassette. The former was digitized using an "off line" laser beam unit (FD 2000, Dupont); the latter was subsequently postprocessed by modifying contrast, optical density and spatial frequencies. Thus, 4 different viewing modalities were obtained for each examination: a) conventional radiography; b) standard digital radiography; c) postprocessed digital radiography; d) digitized conventional radiography. Detectability rates of chest anatomical structures were analyzed by 4 independent radiologists on the different images and expressed by a score 1-4. The values were always higher with digital modalities than with the conventional one and the differences were statistically significant (Student's t-test modified by Bonferroni). In particular, the greatest difference was found between c) and a) in retrocardiac lung parenchyma and in skeletal structures, in favour of c). Concerning the comparative adequacy of the various digital modalities, higher detectability rates of chest anatomical structures were obtained with c), but also with b), than with d). PMID- 1455032 TI - [The use of digital techniques with storage phosphors for orthopantomography. Preliminary note]. AB - Digital panoramic tomographies with light-emitting phosphors were obtained in 39 patients, during a study on the clinical applications of digital imaging. Performing digital panoramic radiographies required the preliminary adaptation of the imaging plates to the cassette holder of the radiographic equipment. The digital images were post-processed according to two different protocols, both of which were recorded for each patient. The former image was quite similar to standard X-ray films and was called "analogic-like". The latter, called "xeroradiographic-like", featured a flattening of the overall contrast together with detail contrast enhancement due to the presence of an edge effect, as it occurs in xeroradiography. Digital panoramic tomography allows a marked reduction in patient's exposure to X-rays. In addition, this technique offers constant high quality results, due to the possibility of recovering over- or under-exposed images during post-processing. Xeroradiographic-like digital films may reduce the sharp contrast that is often present between the anterior and the lateral portions of the maxillary and mandibular arches, thus improving the diagnostic reliability of the examination. Other modalities of digital post-processing may be helpful to depict gingival soft tissues, with obvious advantages for the study of periodontal diseases. PMID- 1455033 TI - [Preoperative needle localization in intraductal breast lesions with galactography]. PMID- 1455034 TI - [Bizarre paraosteal osteochondromatous proliferation. Description of a case]. PMID- 1455035 TI - ["Erdheim-Chester" disease. Description of a case]. PMID- 1455036 TI - [Anomalous left pulmonary artery. Description++ of 2 cases]. PMID- 1455037 TI - [A peculiar case of aneurysm of the portal system]. PMID- 1455038 TI - [A case of adrenal vein leiomyosarcoma. Role of percutaneous biopsy]. PMID- 1455039 TI - [Retractile mesenteritis. Description of a case]. PMID- 1455040 TI - [MR imaging of an intra-abdominal desmoid]. PMID- 1455041 TI - [Echographic nonvisualization of the gallbladder in a case of cholecysto-colic fistula]. PMID- 1455042 TI - [Final scintigraphic diagnosis with [99mTc] HIDA in a case of focal nodular hyperplasia with essential thrombocythemia and portal thrombosis]. PMID- 1455043 TI - [Digestive system radiology: let's not downgrade it]. PMID- 1455044 TI - Disease markers and new therapeutics. Dual objectives of genetics in rheumatology. AB - Genetic studies in rheumatology have led us down a path with two practical endpoints. On the one hand, sophisticated molecular genetics provides specific markers with which to predict disease risk. On the other hand, these same studies have identified likely genetic and molecular intermediates in the pathway of disease, offering new possibilities for targeted intervention and immunotherapy. PMID- 1455045 TI - Prediction of susceptibility to rheumatoid arthritis by human leukocyte antigen genotyping. AB - Recent methodologic advances now allow the precise identification of HLA genes in individuals. Population studies using these methods have pinpointed the HLA alleles strongly associated with rheumatoid arthritis (RA). This article summarizes the current status of these RA-associated HLA genes in disease susceptibility and uses that information to derive estimates of risk ratios for prediction of disease in an individual. PMID- 1455046 TI - Immunoglobulin V genes in rheumatoid arthritis. AB - Recent studies have revealed that a broad spectrum of Ig V genes (VH, V kappa, V lambda) contribute to the rheumatoid factor (RF) and non-RF produced by B cells in patients with rheumatoid arthritis (RA). This result contrasts with the restricted V gene use of paraprotein IgM RF. Certain VH and VL genes, however, appear more often in RA than expected from random expression, including some of the paraprotein-associated V genes. Many V genes expressed in RA are the same as those found in the fetal/CD5+ repertoire, suggesting an important role for CD5+ B cells in RA. Somatic mutations suggest that the B-cell response in RA is at least in part antigen-driven, although many Ig in RA have little or no mutation. Improved detection of V-gene polymorphisms now enable study of Ig V gene RFLP in RA. PMID- 1455047 TI - Immunogenetics of spondyloarthropathies. AB - The association of HLA-B27 with ankylosing spondylitis and related spondyloarthropathies has been known for two decades and has provided a great impetus to the epidemiologic studies and also helped broaden the clinical spectrum of these diseases. The etiology of these diseases is likely to be multifactorial and include genetic, immunologic, and environmental mechanisms. The detailed three-dimensional x-ray crystallographic structure of B27 has now been reported. It has revealed electron density compatible with oligopeptides that are nine amino acid-long (nonamers) bound in the antigen-binding cleft of the molecule. Microsequence analysis of 11 peptides eluted from the antigen binding cleft has confirmed that all are nonamers. The most restricted position in the bound peptide is the second position, where all the 11 peptides contain arginine. The side chain of arginine extends into the B pocket ("45 pocket"), which seems to act as a specificity side pocket in the antigen-binding cleft of the B27 molecule. It is very likely that an understanding of the detailed structure of B27, including the peptide-binding motif and the structural domains recognized by cytotoxic T cells, along with the recent development of the B27 transgenic rat model for spondyloarthropathies, will further enhance our understanding of the immunogenetics of these diseases. It is hoped that this will lead to the source of the arthritogenic triggers and possibly disease prevention by antigen-specific immunomodulation. Because T-cell activation is initiated by the formation of antigen-MHC complexes that are the ligands that are recognized by the antigen-specific T-cell receptor (TCR), it might be possible to inhibit this activation by blocking the antigen-binding cleft of MHC molecules by using high-affinity MHC-binding peptides (MHC blockade) or by a novel, new, and more efficient method of TCR antagonism. PMID- 1455048 TI - Genetics of systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which multiple genes appear to play important roles in pathogenesis. Hereditary deficiencies, both complete and partial, of several components of the complement system clearly predispose to lupus. HLA class II alleles appear to mediate specific autoantibodies, many of which are pathogenic. Modern molecular techniques are now providing insight into the specific major histocompatibility complex class II polymorphisms that are associated with different autoantibodies in SLE. Other genetic systems also may be important. PMID- 1455049 TI - Genetics of the complement system and rheumatic diseases. AB - The complement system, especially the early components of the classic pathway, are critically involved in immune complex processing. The deposition of clusters of complement component C3b on a target marks it for elimination, primarily through an interaction with complement receptors. Not surprisingly, total and partial deficiencies of certain complement components and C3b receptors are associated with rheumatic diseases, particularly systemic lupus erythematosus. This predisposition is explicable, based on the critical role complement plays in immune complex handling. PMID- 1455050 TI - Nerve lesions induced by macrophage activation. AB - The neuropathies associated with infectious processes, including leprosy, retroviral infections and Chagas' disease, represent the largest group of neuropathies in the world. Segmental demyelination and axonal degeneration of nerve fibres are associated with inflammatory infiltrates which contain a large number of mononuclear phagocytes. In order to learn more about the role played by macrophage activation in the nerve lesions observed in inflammatory neuropathies, we have performed a morphological study of nerves injected with products of activation of macrophages including proteolytic enzymes and cytokines (tumour necrosis factor and alpha beta-interferon). We have also studied the effects on nerve fibres of macrophages activated by ingestion of proteose-peptone, a foreign protein, and in the course of a delayed-type hypersensitivity (DTH) reaction. We have found that proteases and urokinase were potent demyelinating agents and that activated macrophages were also able to induce significant demyelination of neighbouring fibres. In contrast, injection of TNF alpha induced more severe nerve lesions consisting of axonal degeneration of the majority of nerve fibres. We thus conclude that infected macrophages which penetrate the endoneurium and macrophages activated in a DTH reaction can both cause neuropathy. PMID- 1455051 TI - Complements, microglial cells and amyloid fibril formation. PMID- 1455052 TI - Distribution pattern and functional state of complement proteins and alpha 1 antichymotrypsin in cerebral beta/A4 deposits in Alzheimer's disease. PMID- 1455053 TI - Complement proteins and complement inhibitors in Alzheimer's disease. PMID- 1455054 TI - Complement activation and beta-amyloid-mediated neurotoxicity in Alzheimer's disease. PMID- 1455055 TI - The role of the acute-phase protein alpha 1-antichymotrypsin in brain dysfunction and injury. AB - The crystal structure of proteolytically modified human ACT has been solved at 2.7-A resolution (Baumann et al., 1991). The final model consists of 374 amino acids, 126 solvent molecules and 5 sugar residues. Asn70 is glycosylated and Asn104 is probably glycosylated. The role of carbohydrates in serpin function may be 3-fold: secretion, removal from circulation and recognition by receptors for complex uptake (Travis et al., 1990). Experiments with recombinant, non glycosylated ACT have shown that glycosylation has no effect on the association rates of ACT with its target proteases (Rubin et al., 1990). The X-ray diffraction studies also revealed that a certain ACT region is involved in DNA binding, although the physiologic relevance of this binding is still unknown. Using a plethora of techniques, scientists are starting to understand the role of ACT in health and disease. It is 14 years since ACT was first purified (Travis et al., 1978) and 9 years since its gene was cloned (Chandra et al., 1983). We have learned considerably about this protease inhibitor in humans and rodents; in inflammation, cancer and AD; as binding to proteases (irreversibly), to the A beta (irreversibly) and to DNA. However, there are still open avenues for research. These include: finding the proteases that ACT inhibits in brain, identifying the cellular receptors which bind ACT-protease complexes and elucidating the DNA-binding phenomenon. Recently, 4 mutations have been found in APP. The first mutation at position 22 of A beta was detected in HCHWA-D by Levy et al. (1991).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455056 TI - The role of perivascular and microglial cells in fibrillogenesis of beta-amyloid and PrP protein in Alzheimer's disease and scrapie. PMID- 1455057 TI - Activated microglia and cerebral amyloid deposits in Alzheimer's disease. PMID- 1455058 TI - Cerebrospinal fluid antibodies: an indicator for immune responses in Alzheimer's disease. PMID- 1455059 TI - Antineurofibrillary tangle, antineural and anti-beta-amyloid-protein in Alzheimer's disease and related disorders. PMID- 1455060 TI - Alzheimer's disease and Down's syndrome antibodies bind to the heavy neurofilament protein of cholinergic neurons. PMID- 1455061 TI - Mycobacteria and AIDS: epidemiological and genetic markers, virulence factors and interactions with the immune system. PMID- 1455062 TI - Mycobacteria as cofactors in AIDS. PMID- 1455063 TI - Epidemiology of mycobacterial diseases in AIDS. PMID- 1455064 TI - Clinical aspects of mycobacterial infections in HIV infection. PMID- 1455065 TI - Antibody levels to the type-specific glycopeptidolipid antigens of Mycobacterium avium in homosexual men: possible implications. PMID- 1455066 TI - Control of disease progress in Mycobacterium avium-infected AIDS patients. PMID- 1455067 TI - Macrophages, mycobacteria and HIV: the role of cytokines in determining mycobacterial virulence and regulating viral replication. AB - The marriage of two scourges, one old (mycobacterial disease) and one new (HIV), has presented an enormous challenge to the medical and public health communities, and has stirred renewed interest in mechanisms for immune control of mycobacterial infection. Virulence of both M. avium and M. tuberculosis appears to be inversely related to the capacity of the microorganisms to induce production of protective cytokines in infected hosts. TNF alpha and IFN gamma are central to this process, and mycobacterial polysaccharides may be their main determinant. Despite these similarities, M. tuberculosis and M. avium cause illnesses at the polar extremes of HIV disease. Tuberculosis, occurring early in the course of HIV disease, may promote HIV replication in otherwise latently infected cells via induction of cytokines. As such, the potential exists for accelerated progression to AIDS due to the mutual synergy of these pathogens. PMID- 1455068 TI - Cytokines, lymphokines, mycobacteria and AIDS. PMID- 1455069 TI - In vitro activity of antimicrobial agents against the Mycobacterium avium complex inside macrophages from HIV1-infected individuals: the link to clinical response to treatment? PMID- 1455070 TI - Mycobacteria and AIDS: treatment, prevention and future prospects. PMID- 1455071 TI - Diminished mephobarbital anticonvulsant action following diphenhydramine pretreatment. AB - Diphenhydramine and other antihistamines produce biphasic effects on drug disposition and lower seizure threshold, thereby potentially diminishing the efficacy of anticonvulsants such as mephobarbital. Accordingly, the influence of diphenhydramine (50 mg/kg, IP) pretreatment on the anticonvulsant activity of mephobarbital (50 mg/kg, IP) was determined in adult female Swiss-Webster mice given pentylenetetrazol (SC). Diphenhydramine lowered the pentylenetetrazol convulsive dose (CD50) by 60%. Administration of diphenhydramine in combination with mephobarbital produced a 65% decrease in the CD50 of pentylenetetrazol in comparison with that of animals given mephobarbital plus pentylenetetrazol. Pharmacokinetic evaluation of mephobarbital blood level data indicates that the mechanism responsible for the observed interaction between diphenhydramine and mephobarbital involves a decrease in mephobarbital uptake from the administration site. PMID- 1455072 TI - Therapeutic parameters of methylprednisolone treatment for retinal photic injury in a rat model. AB - Methylprednisolone (MP) has been prescribed for the treatment of solar retinopathy presumably because of its anti-inflammatory effect. Recently, high doses of MP have been shown to ameliorate light-induced photoreceptor degeneration, and the mechanism of action was suggested to be the inhibition of lipid peroxidation. In this study we examined the dose-response effect and the effect of delayed treatment with MP in an established rat model of retinal photic injury. Animals received intraperitoneal injections of either MP (8, 160, or 320 mg/kg/day) or saline solution (as a control) for 2 days. Injections were started simultaneously with the commencement of light exposure or delayed for 6 or 24 h. The animals were sacrificed 6 days after light exposure, and the retinal damage was assessed by light microscopy and morphometric measurement of the outer nuclear layer (ONL) thickness. Morphologically and morphometrically, treatment with 8 mg/kg/day of MP was not effective, while treatment with 160 mg/kg/day caused better preserved photoreceptors and a thicker ONL compared with the controls (P less than 0.001). Animals administered with a dose of 320 mg/kg/day showed more severe damage to photoreceptors, resulting in a thinner ONL (P less than 0.05). When treatment with 160 mg/kg/day was delayed for 6 h, a similar efficacy as in the no-delay group was noted, but when treatment was delayed for 24 h, no beneficial effect was observed (P = 0.19). Our results demonstrated that early treatment with high doses of MP ameliorated retinal photic injury in rats. PMID- 1455073 TI - The effect of maternal administration of enalapril on fetal development in the rat. AB - Enalapril (MK, 421), an angiotensin converting enzyme inhibitor, was tested for teratogenicity using Wistar rats. The drug was given by oral intubation, from 6 15 days of gestation, at the doses of 0, 3, 10 and 30 mg/kg/day. Reduction in body weight and food consumption were observed in the treated dams. However, food efficiency index, assessed at different periods of gestation was found to be unaffected. On day 20 of gestation, all the dams were sacrificed by cervical dislocation and sign of maternal toxicity, reproduction indices and fetal measures were recorded. The dams treated with enalapril at only the doses of 10 and 30 mg/kg, produced significant decrease in numbers of implants, litter size and incidence of reabsorbed fetuses, and also reduced neonatal growth. No such effects were observed at the lowest dose level (3 mg/kg) used. External, visceral and skeletal examinations of the fetuses of enalapril-treated dams showed several types of variations in all groups, but no consistent pattern were observed. However, a slight increase in skeletal variations was seen with the highest dose (30 mg/kg) group. The data of the present study under the conditions described herein and at the doses employed, revealed no evidence of teratogenesis, but numerous deleterious effects on the fetus were evident. PMID- 1455074 TI - Suppression of intestinal smooth muscle contraction by phenolic compounds. AB - Wood creosote, a mixture of guaiacol, creosol, and other related phenolic compounds, suppresses the spontaneous longitudinal phasic contractions of an isolated rat ileal segment. Thirty-two phenolic compounds were screened for this activity to identify the active substances in wood creosote. Of the 32 compounds tested, 2,3,6-trimethylphenol, 2,4,6-trimethylphenol, and 4-ethylguaiacol were most effective and their respective IC50 values were 0.035, 0.037, and 0.043 mM. Guaiacol and creosol, the chief constituents of wood creosote, were moderately effective and their respective IC50 values were 0.18 and 0.13 mM. Other phenolic compounds in wood creosote also suppressed the ileal contraction although their IC50 values differed markedly from each other. These results suggest that practically all of its constituent phenolic compounds contribute to wood creosote's capacity to suppress ileal contraction. PMID- 1455075 TI - The effect of calcium on disodium monofluorophosphate absorption from the gastrointestinal tract of rats. AB - The absorption of fluoride from disodium monofluorophosphate with or without added calcium has been studied in ligated stomachs and duodena of rats, in vivo. Measurements of fluoride absorption from sodium fluoride were also carried out for comparative purposes. The formation constant of the soluble, neutral calcium monofluorophosphate complex has been determined at 20 degrees, 25 degrees and 37 degrees C. Its value at 37 degrees C being 315 +/- 10 (molar units). The influence of increasing concentrations of calcium on alkaline phosphatase (E.C.3.1.3.1) activity with disodium monofluorophosphate as substrate has been also studied. Gastric absorption of 2 mM disodium monofluorophosphate in the presence of 50 mM calcium was much slower than that of 2 mM disodium monofluorophosphate alone. The latter was slower than that of 2 mM sodium fluoride. The opposite situation has been found for the duodenal fluoride absorption. Results obtained are interpreted in terms of the occurrence of an intestinal monofluorophosphate hydrolysis prior to its absorption as fluoride. In addition, data presented suggest an independent and parallel pathway of fluoride absorption in the form of the liposoluble calcium monofluorophosphate complex. PMID- 1455076 TI - Problems and timing in the removal of silicone oil. AB - The risk associated with silicone oil removal after complex vitreoretinal surgery is unclear. Therefore, a cohort of 87 consecutive cases of silicone oil removal were analyzed. Eyes with attached retina before silicone oil removal with a follow-up of at least 5 months were included into the study. Forty-eight eyes had severe proliferative diabetic retinopathy; 39 eyes had complex proliferative vitreoretinopathy or giant retinal tears after trauma. Additional clinical features included the presence of a secondary cataract or secondary glaucoma in some eyes. The rate of postoperative complications was different in the two groups: 75% of proliferative diabetic retinopathy patients remained attached; of proliferative vitreoretinopathy patients, only 48.5% remained stable. Whereas success was independent of the duration of intraocular silicone oil tamponade in proliferative diabetic retinopathy, removal of silicone oil was more successful in cases of proliferative vitreoretinopathy in which there was a longer period of silicone oil tamponade. Complications occurring usually were severe and led to a loss of visual acuity. The removal of silicone oil from eyes with secondary glaucoma resulted in an improvement in 68% of patients. The rate of vitreoretinal complications after silicone oil removal, even in cases with a clinically stable appearing retina, is rather high. Silicone oil removal therefore has to be considered a procedure posing new and ill-defined risks, especially if the indications for the use of silicone oil as an internal tamponade are rather strict. Exact criteria for the timing and safe removal of silicone oil in these complex vitreoretinal disorders still need to be defined. PMID- 1455077 TI - Identification of silicone oil in the retina after intravitreal injection. AB - Retinal tissue obtained from 2 eyes that had been injected with silicone oil for 2 years was stained with monoclonal antibodies against macrophages and studied by light and electron microscopy and energy-dispersive x-ray analysis. Both specimens showed areas with a relatively intact architecture as well as parts with loss of normal structure. In both areas, immunostaining showed single intraretinal macrophages. Energy-dispersive x-ray results clearly demonstrated that some of the intracellular and extracellular vacuoles within the retina represented the storage sites of silicone. PMID- 1455078 TI - A quantitative in vitro model for silicone oil emulsification. Role of blood constituents. AB - To understand why some patients seem to be protected from emulsification and others are not, the authors developed an in vitro model for quantitative analysis of silicone oil emulsification. The pro-emulsifying potential of substances and blood components that may have access to the vitreous cavity in a patient's eye was analyzed. In this model, red blood cell ghosts had the highest emulsifying effect; plasma and lymphocytes also had a significant emulsifying effect. Phospholipids in membranes and other soluble blood components may play important roles in this process. These results suggest the importance of avoiding and removing hemorrhage and avoiding inflammation when silicone oil is used in vitreoretinal surgery. PMID- 1455079 TI - Experimental evaluation of in vitro stability of purified polydimethylsiloxanes (silicone oil) in viscosity ranges from 1000 to 5000 centistokes. AB - One of the main problems in the clinical use of silicone oil in vitreoretinal surgery is the instability of the material in terms of emulsification. Fine silicone oil droplets can cause a secondary glaucoma by blocking aqueous outflow. Intravitreally applicable silicone oils comprise an inhomogeneous group of materials, and the rate of emulsification depends on the physicochemical properties of the silicone oils. Clinically most frequently used silicone oils are highly purified polydimethylsiloxanes with a viscosity of 1000 centistokes (cs) to 5000 cs. Low-viscosity silicone oils are preferred by some surgeons because of easier surgical handling and easier removal out of the vitreous. The authors investigated highly purified polydimethylsiloxanes in viscosity ranges of 1000 cs, 2000 cs, 3000 cs, 4000 cs, and 5000 cs with regard to their in vitro stability to evaluate the optimal range of viscosity with acceptable material stability. The comparative stability tests were performed with 0.1% salt solutions of albumin, acidic alpha-1-glycoprotein, fibrin, fibrinogen, gamma globulins, and very-low-density lipoprotein as emulsifiers. Silicone oil at 5000 cs was in all cases distinctly more stable than the silicone oils with a viscosity up to 4000 cs. A positive correlation between the degree of viscosity and an increase of material stability was not found with all emulsifiers. When very-low-density lipoprotein, albumin, and fibrin served as detergents, a remarkable stability gain was achieved only at 5000 cs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455080 TI - Systemic antibiotic prophylaxis in penetrating ocular injuries. An experimental study. AB - Intraocular concentrations of systemically administered gentamicin and cefazolin in eyes after a standard penetrating ocular injury were measured to determine the effect of eye injury on ocular pharmacokinetics. Twenty pigmented rabbits were divided into two groups. A standard, 8-mm wound was made at the pars plana of one eye in each animal. Group 1 consisted of 10 rabbits that were treated with cefazolin (75 mg/kg), and Group 2 consisted of 10 rabbits that were given gentamicin (2 mg/kg). Fellow eyes, which sustained no trauma, served as control eyes. All groups received intravenous injections every 8 hours for 72 hours, beginning immediately after repair of the wound. After 72 hours, samples were obtained from the anterior chamber, vitreous cavity, and serum. Standardized bioassays for detection of gentamicin or cefazolin were performed. Significant concentrations of intravitreal cefazolin (9.6 micrograms/ml) and gentamicin (0.60 micrograms/ml) were found in the traumatized eyes in comparison to control eyes (P = 0.0001; P = 0.006). Cefazolin exhibited excellent penetration, achieving concentrations well above minimum inhibitory concentration values for most organisms. Gentamicin levels, however, were well below acceptable therapeutic levels. This study suggests that systemically administered cefazolin can achieve significant intravitreal penetration at minimum inhibitory concentrations after penetrating injury. PMID- 1455081 TI - Subretinal perfluorocarbon liquids. An experimental study. AB - Perfluorocarbon liquids (PFCL) are fully fluorinated, synthetic, transparent compounds with a high specific gravity. These compounds are being increasingly used as an intraoperative tool for repair of complicated retinal detachments. A known complication of their use, however, is liquid entering the subretinal space via a retinal break. The purpose of this study was to evaluate the effects of two of these liquids when placed subretinally in the rabbit eye. Vitrectomy, retinotomy, and subretinal injection of 0.03 cc of either perfluoroctane, perfluorotributylamine, or balanced salt solution (control eyes) were performed on 36 rabbit eyes. Animals were monitored clinically by indirect ophthalmoscopy and fundus photography for up to 21 days. After the 21-day observation period, electroretinograms (ERG) were taken before the rabbits were killed. Histopathologic studies were done at 3 hours, 24 hours, 3 days, 7 days, 14 days, and 21 days after injection. Three eyes demonstrated tearing of the retinotomy site due to downward migration of the PFCL droplet. Results of the ERGs were normal in all animals tested. Phagocytosis of PFCL droplets by the retinal pigment epithelium (RPE) was observed in 1 eye 3 hours after injection. Three of the eyes that received PFCL injections and all of the control eyes demonstrated moderate intracellular edema of both inner and outer nuclear layers as early as 24 hours after injection. In one eye injected with PFCL, these changes progressed to swelling and cystic formation of the inner nuclear layer and mild degeneration of the outer photoreceptor segments 3 days after injection. It was assumed that these effects occurred on a mechanical basis and were not related to PFCL toxicity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455082 TI - The effect of simultaneous internal tamponade on fluid compartmentalization and its relationship to cell proliferation. AB - To determine whether the residual free spaces within the vitreous chamber that result after vitreoretinal surgery and internal tamponade may be avoided, and to verify whether such compartmentalization is of real importance in the recurrence of postoperative proliferative vitreoretinopathy (PVR), the use of simultaneous double filling with polydimethylsiloxane (PDMS) and fluorosilicone (FSiO) in the repair of complicated retinal detachment is evaluated in 12 selected cases. Initial retinal reattachment was achieved in all cases. PVR recurred in 10 patients (83%), 6 of whom showed partial retinal detachment. Inferior and superior postoperative residual free spaces were abolished by this procedure, but a new residual fluid space was created, lying horizontally between the bubbles and expanding in a triangular shape nasal to the optic disc and temporal to the macula. Overall, 9 of 10 eyes with PVR after surgery had proliferation involving these areas. These findings support the concept that compartmentalization is of major importance in determining postoperative cell proliferation. PMID- 1455083 TI - Retinal detachment after refractive surgery for myopia. AB - Refractive surgery has been used widely in some countries for the last 20 years for the correction of myopia. Radial keratotomy and keratomileusis, the most common procedures, may concur with retinal detachment. A total of 14 eyes in 12 patients, 7 after keratomileusis and 7 after radial keratotomy, which had either asymptomatic or symptomatic retinal breaks, subclinical and clinical rhegmatogenous retinal detachments, or both, are discussed here. Five eyes were treated with either laser photocoagulation or cryopexy alone, seven eyes with a scleral buckling procedure, one eye with vitrectomy, and one eye was not operated on. At the final follow-up examination, anatomic reattachment had been achieved in 12 of 14 eyes (85.7%). Visual acuity improved in 3 eyes (21.4%), remained stable in 9 eyes (64.3%), and was worse in 2 eyes (14.3%). The scleral buckling procedures used in the repair of retinal detachment induced refractive changes by modifying axial length and corneal curvature, with recurrence of myopia and astigmatism. Myopia increased a mean of -3.00 diopters in 6 of 7 eyes (86%). Myopic astigmatism power changed a mean of -1.00 diopter in 5 eyes (71%), and the astigmatic axes shifted in 3 eyes (43%). This situation could be prevented with an early peripheral search for and treatment of peripheral retinal degenerative pathologic changes, by avoiding encircling bucklings, or by using alternative methods of treatment. PMID- 1455084 TI - Retinal detachment in eyes with congenital glaucoma. AB - Five patients with congenital glaucoma were treated for complicated retinal detachment. All patients underwent a pars plana vitrectomy and fluid/gas or fluid/silicone exchange. The technical difficulties of operating on buphthalmic eyes are described. Due to subretinal reproliferation, corneal decompensation, and pressure elevation, the functional prognosis is still poor. PMID- 1455085 TI - Management of threshold retinopathy of prematurity. AB - The Cryotherapy for Retinopathy of Prematurity Study demonstrated the benefit of intervention for threshold disease. The authors reviewed their experience with cryotherapy, investigating the questions of treatment for bilateral disease. Between 1985 and 1990, 71 eyes from 41 infants with threshold retinopathy of prematurity were treated. Of the 65 eyes with a minimum of 3 months follow-up, only 7 eyes (11%) progressed to stage 4, although an additional 8 eyes (13%) developed a posterior retinal fold. Although the overall results are comparable to those repeated by the Cryotherapy for Retinopathy of Prematurity Study, the authors recommend treating both eyes if they reach threshold, and treating the two eyes at the same sitting. PMID- 1455086 TI - Applications and limitations of vitreoretinal biopsy techniques in intraocular large cell lymphoma. AB - The cases of 4 patients with clinical signs of intraocular large cell lymphoma are described. Initial cytopathologic examination of vitrectomy specimens failed to establish the malignant character of the vitreous infiltrates. Three of the four patients eventually developed solid central nervous system tumors, intracranial biopsy samples of which revealed large cell lymphoma, 13 months to 42 months after initial examination. In one patient, transscleral retinochoroidal biopsy confirmed the diagnosis at the same time as negative vitreous cytologic examination. Results of cytopathologic examination alone of vitreous biopsy specimens may not be sufficient to make a diagnosis in certain cases of large cell lymphoma that are subsequently documented by CNS biopsy. Careful attention should be paid to the handling, processing, and interpretation of vitrectomy specimens from patients suspected of having intraocular large cell lymphoma. Consideration should be given to immunocytologic staining and interpretation by centers that are highly experienced in vitreous cytopathology. PMID- 1455087 TI - Giant retinal tears. Surgical techniques and results using perfluorodecalin and silicone oil tamponade. AB - Intraoperative use of perfluorocarbon liquids in the management of giant retinal tears was introduced about 4 years ago. Twenty-four patients were operated on for giant retinal tears using perfluorodecalin and silicone oil tamponade. All patients underwent pars plana vitrectomy, unfolding of the giant retinal tears by perfluorodecalin, perfluorodecalin-silicone oil exchange, and endophotocoagulation. The lens was removed in 10 of 14 phakic patients, and encircling scleral buckle was placed in 18 cases. Twenty-three of 24 retinas remained successfully attached with a minimum of 6 months of follow-up. Short term results of intraoperative use of perfluorodecalin and silicone oil tamponade in the management of giant retinal tears are encouraging. Perfluorodecalin offers the advantage of low cost compared with other perfluoro-carbon liquids like perfluoro-n-octane. The exchange with silicone oil offers the advantages of easy removal of perfluorodecalin and absence of posterior slippage of the retinal tear. PMID- 1455088 TI - An overview of potential applications of heparin in vitreoretinal surgery. AB - Heparin is a naturally occurring complex polysaccharide with properties that lend themselves to the potential treatment of proliferative ocular disorders. The biochemistry of heparin and its effects on the eye and cultured ocular cells under varied experimental conditions are discussed. PMID- 1455089 TI - The lowest effective dose of tissue plasminogen activator for fibrinolysis of postvitrectomy fibrin. AB - Tissue plasminogen activator (tPA) has been shown to be effective at a dose of 25 micrograms in the treatment of severe postvitrectomy fibrin. However, a recent report based on an animal model indicates that retinal toxicity may occur at doses as low as 25 micrograms. This study uses a low dose (1.5 micrograms to 3 micrograms) of tPA for 34 injections in 26 eyes, and determines the lowest effective dose to be between 1.5 and 3 micrograms. Complete fibrinolysis was achieved in all 28 eyes in which 3 micrograms of tPA was administered within 10 days of vitrectomy, whereas partial fibrinolysis was achieved in eyes treated with 3 micrograms of tPA 27 days and 82 days after vitrectomy. Complete fibrinolysis occurred in only 1 of 4 eyes that receive 1.5 micrograms of tPA. A dose of 3 micrograms of tPA is recommended for treatment of severe fibrin after vitrectomy, as it has a wider margin of safety than do higher doses. PMID- 1455090 TI - Can the diode laser (810 nm) effectively produce chorioretinal adhesion? AB - In this study, argon green (514 nm), krypton red (647 nm), and diode (810 nm) lasers were used to produce transpupillary photocoagulations on rabbit chorioretina to simulate a retinal buckle treatment. To evaluate the efficacy of the diode laser in creating a retinopexy effect, the morphologic aspects of the acute lesions and scar development were compared. The study of the acute lesions revealed that the chorioretinal thermal damage produced by the argon green laser involved all the retinal layers and the retinal pigment epithelium. The use of the krypton red and the diode lasers resulted in deeper chorioretinal thermal damage. Two months after the treatments, all the lesions resulted in adhesive chorioretinal pigmented scars. However, the diode lesions produced a deeper scar, characterized by marked chorioretinal atrophy. PMID- 1455091 TI - A new device for pupillary dilatation in vitreous surgery. AB - A completely new surgical technique to obtain pupillary dilatation is presented. It permits achievement of a mydriasis sufficient to observe the vitreous cavity in both phakic and aphakic eyes during vitreous surgery. Miotic immobile pupils not dilatable pharmacologically are enlarged by means of a silastic ring with a C shaped groove on its outer part. This is introduced into the eye through a limbic opening. When in place, the external sulcus of the ring hosts the pupillary rim. Twelve patients (three phakic and nine aphakic) were treated. In two patients operated upon previously with silicone oil tamponade, some difficulties were encountered during the insertion of the device owing to the lubricating effect of the oil. After the removal of the ring, all the pupils returned to a round shape, with no apparent damage to the iris structure. PMID- 1455092 TI - Artificial iris diaphragm and silicone oil surgery. AB - In order to avoid contact between silicone oil and the cornea and subsequent painful corneal dystrophy in aniridial eyes, an artificial iris diaphragm was constructed. It consists of polymethylacrylat (PMMA) and simulates the situation of the iris with a central pupillary opening and inferior iridectomy. To date, these diaphragms have been implanted in 11 cases of the severest ocular trauma with accompanying aniridia and proliferative vitreoretinopathy. In the presence of sufficient residual secretion of the ciliary body (9 cases), the diaphragm assumes the function of normal iris and prevents the silicone oil from coming into contact with the corneal endothelium. The transparent diaphragm ensures a view through to the fundus. In the early postoperative period, there was, as anticipated, a fibrinous reaction in the area of the anterior segment. PMID- 1455093 TI - Discharge of pulmonary rapidly adapting stretch receptors during HFO ventilation. AB - High-frequency oscillatory ventilation (HFOV) has been shown to stimulate slowly adapting pulmonary stretch receptors (PSR) and thereby to inhibit spontaneous breathing, i.e. HFOV prolongs expiration or even elicits normocapnic apnea. However, during HFOV respiratory effects possibly mediated by pulmonary rapidly adapting receptors (RAR) have also been observed, e.g., diaphragmatic activation or augmented breaths. Therefore, we analyzed HFOV-induced changes in RAR activity in anaesthetized rabbits by mean of single fibre preparations of vagal RAR afferents. HFOV was applied in several combinations of airway pressure (Paw) and oscillation frequency (fOsc). In the sample of 60 RAR fibres prepared in 20 rabbits we found a wide spectrum of discharge patterns during HFOV. The inspiratory discharge rate during HFOV was increased in 38, decreased in 10, and unchanged in 12 RAR. The expiratory discharge rate was increased in 34, decreased in 17, and unchanged in 9 RAR. The effects of gradually changing Paw or of fOsc during HFOV were different in different fibres. In 17 fibres both inspiratory and expiratory discharge rates rose with increasing Paw during HFOV, whereas 19 fibres were not affected by increasing Paw. In some fibres either the inspiratory (12) or the expiratory (9) activity was inhibited in proportion to increasing Paw. From these results we conclude, that (a) the changes of RAR activity during HFOV are heterogeneous and the reflex effects of RAR stimulation may be balanced by RAR with decreased activity; (b) this heterogeneity of RAR discharge patterns explains the dominancy in the control of breathing during HFOV of the homogeneously stimulated PSR; and (c) depending on HFOV ventilatory parameters used the overall RAR stimulation may be strong enough to overrule the inspiration inhibiting effects of PSR. PMID- 1455094 TI - Ontogenetic modification of the hypercapnic ventilatory response in the zebra finch. AB - We investigated the effect of exposure to CO2 during development on the adult ventilatory response to CO2 of zebra finches. Developing zebra finches were exposed to chronic hypercapnic respiratory environments as embryos, as nestlings or during both developmental periods. Their responsiveness to CO2 was then measured following a 125-135 day post-fledging deacclimation period. At a FICO2 of 0.06, mean ventilation of adult finches in the three groups was 74.8, 61.3 and 65.8%, respectively, of that of finches reared under normocapnic conditions. These data indicate that adult acute ventilatory responsiveness to CO2 in birds may be in part determined by CO2 exposure during early development and may help explain the observation that fossorial and semifossorial species of birds and mammals, that naturally encounter high CO2 conditions in their burrows, have a blunted hypercapnic ventilatory response. PMID- 1455095 TI - Reduced tidal volume increases 'air hunger' at fixed PCO2 in ventilated quadriplegics. AB - The act of breathing diminishes the discomfort associated with hypercapnia and breath-holding. To investigate the mechanisms involved in this effect, we studied the effect of tidal volume (VT) on CO2-evoked air hunger in 5 high-level quadriplegic subjects whose ventilatory capacity was negligible, and who lacked sensory information from the chest wall. Subjects were ventilated at constant frequency with a hyperoxic gas mixture, and end-tidal PCO2 was maintained at a constant but elevated level. VT was varied between the subjects' normal VT and a smaller VT. Subjects used a category scale to rate their respiratory discomfort or 'air hunger' at 30-40 sec intervals. In 4 of 5 subjects there was a strong inverse relationship between breath size and air hunger ratings. The quality of the sensation associated with reduced VT was nearly identical to that previously experienced with CO2 alone. We conclude that afferent information from the lungs and upper airways is sufficient to modify the sensation of air hunger. PMID- 1455096 TI - Molecular adaptation of hemoglobin function in mammals. AB - Vertebrate hemoglobins are tetramers made of two pairs of alpha and beta subunits each containing a hydrophobic pocket where a heme molecule binds tightly and allows for the reversible binding of oxygen. Both tertiary and quaternary structures are ideally suited for the loading and unloading of oxygen necessary for the metabolic requirements of the organisms. Starting from a single ancestor hemoglobin subunit, evolutionary processes have led to heterologous tetramers exhibiting a moderate oxygen affinity due to heme-heme interaction (allosteric mechanism) which may be further modulated through electrostatic interactions with chloride and/or organophosphate anions present in the red cells. These effectors, which bind preferentially to the deoxy-Hb tetramers at a distance from the heme groups, play a major role in the adaptation of the respiratory properties of hemoglobin to either allometric-dependent oxygen needs or to various hypoxic environments such as altitude, burrowing, or foetal life. In most cases the existence or the strength of the effector-Hb complexes, hence the changes in the allosteric equilibrium, may be ascribed to one or a few mutations of residues at the effector binding sites. Typical examples of these mechanisms are described. PMID- 1455097 TI - Respiratory-associated rhythmic firing of midbrain neurons is modulated by vagal input. AB - We recorded phrenic nerve activities and single unit firings of mesencephalic neurons in 19 decerebrate, paralyzed and ventilated cats, in which the spinal cord had been transected at C7-T1 and carotid sinus nerves cut but vagus nerves left intact. After we had found neurons with respiratory-associated rhythmic activity, we tested the effect of changing pulmonary vagal input by (1) stopping and restarting the ventilator; (2) changing the ventilator's tidal volume; (3) progressively cooling the vagus nerves to 6-7 degrees C; and (4) vagal section. All methods of testing yielded results that showed that vagal input, probably from pulmonary stretch receptors, tonically inhibits the respiratory-associated firing of the mesencephalic neurons by a direct mechanism that is independent of a vagal effect on medullary respiratory drive. We have suggested that these neurons are involved in the mechanism that conveys information about respiration to the cortex where it may be interpreted as the sensation of dyspnea. If so, movement and increased expansion of the lungs can be expected to lessen the sensation. PMID- 1455098 TI - Phrenicotomy in the rat: acute changes in blood gases, pH and body temperature. AB - Adult male rats were used to compare blood gases, pH and body temperature (Tb) before and after acute bilateral phrenicotomy. Under anaesthesia a femoral artery was catheterised and ties were placed round the phrenic nerves of seven rats (PNX group), while in five rats the ties were placed in the vicinity of the phrenic nerves (SHAM group). Twenty-four hours after surgery arterial blood samples were collected during quiet wakefulness (QW) and grooming (G), before and 1 h after the ties were pulled, and analysed for PO2, PCO2 and pH. No changes were detected in the SHAM samples taken before and after the ties were pulled. In the PNX group a significant decrease in Tb occurred (QW, 0.6 degrees C; G, 1.5 degrees C). Following PNX PaO2 decreased by 11.2 mmHg (QW) and 10.0 mmHg (G); PaCO2 increased by 2.6 mmHg (QW) and 2.4 mmHg (G) and pH fell by 0.04 (QW) and 0.03 (G). All changes except in PaCO2 (QW) were significant. It is concluded that the changes in Tb, blood gases and pH which follow phrenicotomy in the rat are due to an increase in dead space ventilation (VD) and a small reduction in alveolar ventilation (VA) associated with a faster, shallower pattern of breathing. PMID- 1455099 TI - Afferent innervation and receptors of the canine extrathoracic trachea. AB - The aim of this study was to establish the cranio-caudal distribution of slowly (SAR) and rapidly (RAR) adapting receptors of the extrathoracic trachea (ETT) as well as their innervation and response to water solutions of different compositions. Experiments were carried out on anesthetized dogs breathing spontaneously through a low cervical tracheostomy. Eighty percent of SARs and 76% of RARs with fibers in the superior laryngeal nerve (SLN) were found in the cranial third of the ETT. Fifty-seven percent of SARs and 45% of RARs with fibers in the cervical vagus and/or recurrent laryngeal nerve (RLN) were localized in the caudal third of the ETT. Instillation of water into the tracheal lumen had no effect on the activity of any SAR tested, but stimulated 41% of the RARs with fibers in the SLN and 23% of the RARs with fibers in the cervical vagus. Some of the RARs with fibers in the SLN (24%), but none of those with fibers in the cervical vagus/RLN, responded also to iso-osmotic dextrose solutions. Trachealis muscle contraction failed to stimulate the RARs tested. The blocking temperature for SAR and RAR fibers was similar and well within the range of myelinated fibers. We conclude that the SLN provides the innervation of the cranial ETT while the RLN has fibers for the caudal ETT with some overlap in the middle. The responses to water solutions indicate that tracheal RARs constitute a more heterogeneous group than laryngeal RARs. PMID- 1455100 TI - Phase differences between chest and mouth flows in patients suffering from pulmonary disease. AB - The phase difference (PD) between mouth flow and chest flow during rest breathing was measured in pulmonary diseased patients using a body box and the results were compared with normal subjects. Whereas the PD increased in patients with chronic pulmonary obstructive disease (COPD) compared to normal subjects, PD was found to be normal in patients with interstitial pulmonary fibrosis (IPF) (Normal: 2.94 +/ 1.25, COPD: 11.32 +/- 4.17*, IPF: 2.62 +/- 1.67 degrees; *P < 0.01). PD correlated well with FEV1.0/VC%, PFR, RV/TLC, VTG and Ra (r: -0.759, -0.672, 0.788, 0.666, 0.606). From an in-depth analysis of the results, we suggest that the factors which increase PD in COPD patients include hyperinflation of the lung, increases in airway resistance and increases in the parallel inhomogeneity of airway resistance accompanied by an unevenness of alveolar pressures. PD was thought to be clinically useful for the evaluation of the pathological stages of COPD because it reflects the overall clinical manifestations in COPD patients. PMID- 1455101 TI - Mechanical characteristics and functional length of canine expiratory muscles. AB - The expiratory muscles of the abdominal region actively contribute to breathing. In dogs, the transversus abdominis appears to be the main abdominal muscle of expiration. The in vitro mechanical properties of the transversus abdominis have not been reported to date, and formed the basis of the present investigation. Moreover, in order to understand better the nature of the mechanical interplay between the various abdominal muscle groups, we also evaluated the effects of posture on the operational length of canine transversus abdominis and external oblique muscles and related their in situ length to optimal length. The experiments were performed on twelve mongrel dogs, anesthetized with pentobarbital sodium. Contractile properties of excised transversus abdominis muscle strips were evaluated at 37 degrees C and revealed similar twitch, force frequency and length-tension properties as previously reported in canine external oblique (Farkas and Rochester, J. Appl. Physiol. 65: 2427-2433, 1988). In the supine posture, we noted that external oblique was operating at 88% Lo, while the transversus abdominis was operating at a significantly shorter length of 74% Lo. Thus, in the supine posture, the external oblique is better situated than the transversus abdominis to generate tension. In the prone posture, however, we noted that both abdominal muscles were located at similar positions along their length-tension curve, operating at a length of roughly 77% Lo. Since both muscles share common length-tension characteristics, the present results indicate that the tension generating potential of both muscles in prone dogs is equal for a given neural input. However, we conclude that the preferential recruitment of the transversus abdominis in prone animals must be related to factors other than simple tension generation. PMID- 1455102 TI - Respiratory-associated thalamic activity is related to level of respiratory drive. AB - We recorded phrenic nerve activity and thalamic single unit firing in unanesthetized, suprathalamically decerebrated, paralyzed and ventilated cats, in which vagi and carotid sinus nerves (CSN) had been ablated. Seventy-six (14%) of 545 neurons in regions of the thalamus related to the ascending reticular system, which had been tonically firing at low respiratory drives, developed rhythmic increases of firing associated with each respiration when drive had been increased by CSN stimulation or hypercapnia. The increases of neuronal firing occurred in late inspiration/post-inspiration but sometimes lasted into expiration; the magnitude of change was graded according to the magnitude of respiratory activity. Thalamic neurons also fired with a rhythm related to ventilator-induced chest expansion, some units showing both the respiratory associated and the ventilator-related rhythms. Simultaneously recorded mesencephalic and thalamic neurons developed similar rhythms when drive was increased. We suggest that these neuronal activities reflect the conveyance of information about respiration to the cortex, where it may lead to the sensation of dyspnea and perhaps to arousal. PMID- 1455103 TI - Management of bacterial meningitis in children and adults. PMID- 1455104 TI - Viral meningitis and encephalitis. PMID- 1455105 TI - Human transmissible neurodegenerative diseases (prion diseases). PMID- 1455106 TI - Poliomyelitis and the postpolio syndrome. PMID- 1455107 TI - Neurologic Lyme disease. PMID- 1455108 TI - Neurosyphilis. PMID- 1455109 TI - Rickettsial infections of the central nervous system. PMID- 1455110 TI - Neurologic complications of infective endocarditis. PMID- 1455111 TI - Chronic meningitis. PMID- 1455112 TI - Neuroradiology of intracranial infection. PMID- 1455113 TI - Brain abscess. PMID- 1455114 TI - Star: Karl Stern (1906-1975). PMID- 1455115 TI - [What is your diagnosis? Janeway lesions as manifestation of a septic-embolic disorder in streptococcal endocarditis]. PMID- 1455116 TI - [Cancer research in clinical practice. The attentive physician and the family anamnesis]. AB - Astute physicians play an important role in the detection of cancer causes. Their most powerful tool is the family history. It permits the identification of families with unusual cancer clusters. The members of such families can be recruited for research in prevention and molecular genetics. The potential of research in medical practice should be exploited more extensively in the future. PMID- 1455117 TI - [Indications for, technique and interpretation of arterial Doppler sonography from the vascular surgeon's viewpoint]. AB - Doppler sonography is one of the most important diagnostic tools for angiologists and vascular surgeons and also for general practitioners with an interest in vascular disease. It can be carried out easily and at low cost and, at the same time, provides reproducible, quantitative data on which further diagnostic and therapeutic decisions can be based. First, systolic arterial pressures in the anterior and posterior tibial and in the peroneal arteries are measured, with the Doppler probe placed at ankle level. A cuff is wrapped around the lower leg and inflated until the Doppler signal disappears. The highest value measured in each leg is termed ankle pressure. Division of the latter by systolic brachial pressure results in the so-called ankle-brachial index or "ABI". Ankle pressure and ABI correlate well with clinical findings. In normal individuals it is greater than 1. In claudication it ranges between 0.3 and 0.9, in patients with resting pain between 0.1 and 0.5 and with ischemic tissue loss between 0.0 and 0.2. After angioplastic or surgical revascularization procedures, a fall of the ABI by 0.15 or more is an indication of relevant hemodynamic deterioration and, therefore, calls for further investigation by arteriography or color duplex sonography. PMID- 1455118 TI - [Precordial pain, dyspnea and rapidly fatal development in a 34-year-old HIV positive patient]. PMID- 1455119 TI - [Manual medicine of the spine--indication, diagnostic and therapeutic possibilities]. AB - Manual medicine developed rapidly during the last 40 years and became an integral part of standard medicine. The basic idea behind the methods used is that several acute and chronic disorders the spine and peripheral articulations are caused by functional disturbances in one or more spinal motion segments, and also in peripheral joints, always accompanied by reflectory muscular reactions. These changes must be detected and treated specifically. The diagnosis for manual therapy is always complementary to general medical examination. Knowledge of absolute and relative contraindications is the basis for every manual therapy. Therapeutically, apart from the actual mobilization with or without impulse, the so-called neuromuscular techniques are used; these are acting together with the muscle force of the patient and with the thereby triggered reflex-mechanisms. Whereas the latter techniques are also used in physiotherapy, mobilization with impulse should be practised nowadays only by trained physicians and chiropractitioners, since the risks involved are considerable. It is of great importance that the therapy is not limited just to the manipulation of the functionally disturbed motion segment but that in addition muscular disbalance is treated. PMID- 1455120 TI - [Liquid hand soap which kills HIV viruses]. PMID- 1455121 TI - Multiple sleep latency tests during the constant routine. AB - The "post-lunch dip" is a common behavioral phenomenon, though perhaps a misnomer. Biphasic models of the human sleep tendency rhythm suggest an alternative explanation for the afternoon decline in alertness. Sleep tendency was measured with the Multiple Sleep Latency Test (MSLT) at 2-hour intervals in 16 volunteers from three age groups (ages 10-12, ages 16-17, ages 62-74 years) during a constant routine in which small meals were given each hour. Baseline scores showed no significant Time of Day effect, although a trend for an afternoon dip was present in the eldest group. During the constant routine, a significant Time of Day effect was found for the two older groups and not for the prepubertal group. The results indicate a midday increase in sleep tendency that is unrelated to food intake but that may be related to developmental or maturational processes. PMID- 1455122 TI - Precise conservation of NREM period 1 (NREMP1) delta across naps and nocturnal sleep: implications for REM latency and NREM/REM alternation. AB - The delta integrated amplitude (DIA) in nonrapid eye movement period 1 (NREMP1) of daytime naps was precisely subtracted from the NREMP1s of ensuing nocturnal sleep, indicating that the brain can retain a record of DIA expressed in sleep episodes initiated 12.5 and 8.5 hours before nocturnal sleep onset. The DIA subtraction was primarily accomplished by reduced NREMP1 duration [earlier rapid eye movement (REM) onset], suggesting that the timing of REM period 1 (REMP1) onset is controlled by delta need. This result is consistent with the hypothesis that REM sleep occurs when a stimulus for NREM has been partially depleted. PMID- 1455123 TI - Spontaneous ventilation and respiratory motor output during carbachol-induced atonia of REM sleep in the decerebrate cat. AB - Microinjections of carbachol into the pons induce a state that resembles rapid eye movement (REM) sleep in intact cats and, in decerebrate, artificially ventilated cats, produce postural atonia accompanied by a powerful depression of the respiratory motor output. In this study, pontine carbachol was used in decerebrate, spontaneously breathing cats to assess the effects of mechanical and chemical respiratory reflexes on the magnitude and pattern of the carbachol induced depression of breathing, and to determine whether the depression is altered in those animals in which rapid eye movements are present. Phrenic nerve activity and tidal volume were only transiently depressed at the onset of the carbachol-induced postural atonia, whereas the decrease in respiratory rate and the depressions of hypoglossal and intercostal activities persisted until the response was reversed by a pontine microinjection of atropine 15-101 minutes after the onset of carbachol response. Ventilation was reduced to 70% of control during the steady-state conditions. The irregularity of breathing, characterized by the inter-quartile ranges of the distributions of the peak phrenic nerve activity and respiratory timing, did not increase following pontine carbachol. Neither vagotomy nor vigorous eye movements were associated with increased breathing irregularity. This contrasts with the irregular breathing (with minor average changes in ventilation) typical of natural REM sleep. We propose that the carbachol-injected decerebrate cat provides a useful model of the depressant effects that neural events associated with REM sleep may have on breathing. PMID- 1455124 TI - DQB1-0602 (DQw1) is not present in most nonDR2 Caucasian narcoleptics. AB - Human narcolepsy is a genetically determined disorder of sleep strongly associated with the human leucocyte antigens (HLA) DR2 and DQw1. In black narcoleptic patients, susceptibility for narcolepsy is more closely related to a specific gene subtype of DQw1, DQB1-0602, than to DR2. About 30% of black narcoleptic patients are nonDR2, but all carry the HLA DQB1-0602 gene. In the present study, we have tested caucasian nonDR2 cataplectic patients (6 sporadic cases and 7 familial cases from 3 multiplex families) for the presence of the HLA DQB1-0602 and DQA1-0102 (DQw1) using a specific polymerase chain reaction (PCR) oligotyping technique. None of the patients was DQB1-0602 or DQA1-0102 positive, thus proving that, in caucasians, DQB1-0602 and DQA1-0102 (DQw1) are not prerequisites for the diagnosis of narcolepsy. Further studies with more patients are warranted to exclude the possibility that a few caucasian patients carry rare haplotypes with DQB1-0602 independently of DR2. PMID- 1455125 TI - Plasma renin activity and sleep-wake structure of narcoleptic patients and control subjects under continuous bedrest. AB - In order to determine if renin release would be affected by a dysfunction of the circadian and ultradian organization of sleep, 24-hour profiles of plasma renin activity (PRA) concomitant with sleep stages were established in 10 normal subjects and nine narcoleptic patients, with 10-minute blood sampling intervals. Mean PRA levels were similar in control subjects and narcoleptic patients. Individual 24-hour profiles revealed that the previously described association between renin oscillations and sleep stage alternations was preserved. Increased PRA release was observed during the transition from rapid eye movement (REM) sleep or waking periods to nonrapid eye movement (NREM) sleep, and REM sleep occurred as PRA levels were decreasing. Thus, PRA curves exactly reflected the irregularities and disturbances in the sleep structure of the narcoleptic patients. The 24-hour PRA profiles of the patients did not show the general upward trend during nighttime sleep, which is probably induced in the control subjects by the repetitive recurrence of longer episodes of undisturbed NREM sleep. Because of marked sleep fragmentation in the patients, the duration of NREM sleep was often insufficient to allow for the occurrence of a significant PRA increase. Because sleep onset REM (SOREM) episodes, characteristic of narcolepsy, are not preceded by NREM sleep and its associated increase in PRA, no relative PRA decline occurred during this type of REM sleep. In conclusion, the 24-hour PRA profiles of the narcoleptic patients reflected exactly their sleep stage distribution, confirming previous findings that PRA oscillations appear to be inseparable from the NREM-REM sleep cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455126 TI - Sleepiness/alertness on a simulated night shift schedule and morningness eveningness tendency. AB - This study examined the influence of morningness-eveningness on night shift sleepiness in 15 subjects. Sleepiness was assessed during a five-night protocol involving the multiple sleep latency test (MSLT), repeated test of sustained wakefulness (RTSW) and the Stanford Sleepiness Scale (SSS). Daytime sleep was estimated by sleep diaries and wrist actigraphy. The sample was divided by median score on the Horne and Ostberg Morningness-Eveningness Questionnaire. Physiological sleep tendency was significantly worse between 0030 and 0430 hours for the Morning Tendency group than for the Non-Morning Tendency group. The Morning Tendency group reported obtaining less daytime sleep than the Non-Morning Tendency group; however, there was no difference between groups in total daytime sleep estimated by actigraphy. This preliminary study suggests that morning types are sleepier during night shift hours than non-morning types. PMID- 1455127 TI - Melatonin rhythms in night shift workers. AB - For some time, it has remained uncertain whether the circadian rhythms of permanent night shift workers are adapted to their night-active schedule. Previous studies of this question have often been limited by "masking" (evoked) effects of sleep and activity on body temperature and cortisol, used as marker rhythms. In this study, the problem of masking was minimized by measuring the timing of melatonin production under dim light conditions. Nine permanent night shift workers were admitted to the Clinical Research Center (CRC) directly from their last work shift of the week and remained in dim light while blood samples were obtained hourly for 24 hours. Melatonin concentrations were measured in these samples using a gas-chromatographic mass-spectrometric method. Sleep diaries were completed for two weeks prior to the admission to the CRC. Overall, the onset of the melatonin rhythm was about 7.2 hours earlier (or 16.8 hours later) in the night workers compared to day-active controls. It was not possible to know whether the phase of the melatonin rhythm was the result of advances or delays. In night shift workers, sleep was initiated (on average) about three hours prior to the onset of melatonin production. In contrast, day-active subjects initiated sleep (on average) about three hours after their melatonin onset. Thus, the sleep times selected by night shift workers may not be well synchronized to their melatonin rhythm, assumed to mark the phase of their underlying circadian pacemaker. PMID- 1455128 TI - Comparison of EEG sleep measures in healthy full-term and preterm infants at matched conceptional ages. AB - Continuous electroencephalogram (EEG) sleep studies were obtained on healthy full term and preterm infants at matched conceptional ages. Studies were recorded under environmentally controlled conditions. Eighteen healthy preterm infants were matched to 18 full-term infants based on conceptional age, sex, race and socioeconomic class. The initial 3 hours of a 12-hour recording were simultaneously recorded on paper and computer. The visually scored data based on the paper recordings for sleep architecture and continuity measures were studied. Differences in each sleep organization for the preterm infants included the following: a longer ultradian sleep cycle (70 minutes vs. 53 minutes, p = 0.02) was noted. More abundant trace alternant (34% vs. 28%, p = 0.02) and less abundant low-voltage irregular active sleep (13% vs. 17%, p = 0.05) were noted. Although no differences were observed for sleep latency and efficiency, the preterm infants had fewer numbers and shorter durations of arousals, fewer body movements and rapid eye movement (REM) (p < 0.01), particularly during quiet sleep. The extrauterine experience or the earlier birth of the preterm infant may influence specific sleep architecture and continuity measures when compared with the sleep of full-term infants who experienced a complete intrauterine gestation. PMID- 1455129 TI - A longitudinal study of sleep stages in young women during pregnancy and postpartum. AB - We conducted a longitudinal polysomnographic study in five healthy primiparous subjects, whose sleep was first recorded between 8 and 16 weeks of gestation, then every 2 months until parturition and at 1 month postpartum. The first 6 hours of sleep were used for statistical analysis. In contrast to previous studies, we found no reduction in stage 4 sleep with pregnancy. Slow-wave sleep (comprising stages 3 and 4), was significantly higher at 27-39 weeks of gestation than at 8-16 weeks, as predicted by the restorative theory of sleep. There was no significant difference in rapid eye movement (REM) sleep time. When compared to a group of normal ovulating women, however, REM sleep time decreased during the last two months of pregnancy and, although there was no change in sleep onset latency, the time spent awake during the first six hours of sleep was increased. Future research into the effects of cortisol and progesterone is indicated. PMID- 1455130 TI - Automatic sleep/wake identification from wrist activity. AB - The purpose of this study was to develop and validate automatic scoring methods to distinguish sleep from wakefulness based on wrist activity. Forty-one subjects (18 normals and 23 with sleep or psychiatric disorders) wore a wrist actigraph during overnight polysomnography. In a randomly selected subsample of 20 subjects, candidate sleep/wake prediction algorithms were iteratively optimized against standard sleep/wake scores. The optimal algorithms obtained for various data collection epoch lengths were then prospectively tested on the remaining 21 subjects. The final algorithms correctly distinguished sleep from wakefulness approximately 88% of the time. Actigraphic sleep percentage and sleep latency estimates correlated 0.82 and 0.90, respectively, with corresponding parameters scored from the polysomnogram (p < 0.0001). Automatic scoring of wrist activity provides valuable information about sleep and wakefulness that could be useful in both clinical and research applications. PMID- 1455131 TI - Serum prolactin response to a D2 antagonist in narcoleptic and control canines. PMID- 1455132 TI - Bibliography of recent literature in sleep research. Citations retrieved by brain information service. PMID- 1455133 TI - [Different varieties and anatomopathological description of primary tumors of the liver]. AB - The different types of primary hepatic tumors are examined, focusing on their macroscopic and histologic features. A large variety of neoplasms can be observed, derived from the different components of the liver. Benign (adenoma, focal nodular hyperplasia) or malignant (hepatocellular carcinoma) epithelial tumors of hepatocellular origin are very common. Hemangioma is the most common mesenchymatous-derived tumor. However, the frequency of each type of tumor varies considerably in the different age and sex groups. Some special entities recently reported, such as epithelioid hemangioendothelioma or fibrolamellar carcinoma are detailed. PMID- 1455134 TI - [Clinical symptomatology and radiological aspects of primary cancers of the liver]. AB - Hepatocellular carcinoma is a malignant tumor derived from hepatocytes. It is the most frequent of primary liver cancers. In 90% of the cases, it occurs in a cirrhotic liver and is now more and more detected by ultrasonographic screening of cirrhotic patients. Hepatocellular carcinoma can also be diagnosed at a more advanced stage, when complications, such as ascites, jaundice or digestive hemorrhage, occur. CT scan and magnetic resonance imaging are useful to confirm ultrasonographic findings, but angiography with infusion of Lipiodol in hepatic artery followed by CT scan remains the most sensitive method for diagnosis. Intrahepatic cholangiocarcinoma is derived from intrahepatic bile duct cells and does not occur in a preexisting cirrhotic liver. Diagnosis is usually late. Clinical features are those of hepatic malignancy with jaundice and abdominal pain. Morphological examination of the liver shows an intrahepatic tumor, sometimes associated with a dilatation of the surrounding bile ducts. Other primary malignancies are very rare. Fibrolamellar carcinoma presents as an abdominal mass occurring in a young adult with a non cirrhotic liver. Prognosis is better than that of hepatocellular carcinoma. Cystadenocarcinoma is a cystic tumor of bile ducts that can develop in a preexisting cystadenoma. Angiosarcoma is a highly malignant tumor derived from sinusoidal endothelial cells. Exposure to various carcinogens is found in 30% of the cases. Epithelioid hemangio endothelioma differs from angiosarcoma by its occurrence in young adults and a more favorable prognosis. PMID- 1455135 TI - [Cine-MRI. Non-invasive new imaging of the heart]. PMID- 1455136 TI - [Hemophilus vaccines. At last effective protection]. PMID- 1455137 TI - [Advantages and difficulties of aerosol therapy]. AB - Aerosolization of drugs may be designed to treat lower respiratory tract and bronchial diseases and more recently infectious diseases of the lungs. The use of drug aerosol has been limited by the relative lack of knowledge about the fate of inhaled drugs. It depends on the specifications of the aerosol, the drug itself, the conditions of aerosolization, and the presence of lung disease. The advantage of the airways route is that treatment effects are obtained without systemic effects. PMID- 1455138 TI - [Vasomotricity of normal and atheromatous coronary arteries]. AB - In order to fulfil, at any time, the myocardium requirements for oxygen and energy, the coronary circulation must be able of extremely intense and rapid vasodilation. This circulation undoubtedly is the body's regional circulation that "works" in the most difficult anatomical and physiological conditions. Coronary vasomotricity is regulated by three different systems operating synchronously. Metabolism-mediated vasodilatation, with adenosine as principal mediator, essentially concerns the small-caliber intramyocardial arterioles and is the predominant regulatory system in normal subjects. Nervous regulation (sympathetic and parasympathetic systems) exclusively concerns the wide, epicardial coronary arteries; it plays a modest, but non-negligible, role in normal subjects but becomes very important in patients with stenosis of the epicardial coronary arteries. Endothelium-mediated regulation, discovered about 10 years ago, seems to play a crucial role. Under the influence of haemodynamic and humoral stimuli, the endothelium synthesizes and releases substances which stimulate the underlying vascular smooth muscle. Nitric oxide (NO), or EDFR1, is the best known, but not the only messenger of vasodilatation; beside its relaxant effect on the smooth muscle, it exerts a potent platelet antiaggregating action. The functioning of these regulatory systems is deeply perturbed by atheroma of the coronary arteries: in addition to the fixed haemodynamic obstacle due to atheromatous stenosis, there is a diffuse decrease of endothelial functions and a rise in sensitivity to nervous vasoconstrictor stimuli. PMID- 1455139 TI - [Development of gynecologic surgery. Consequences of the hospital use of endoscopic methods]. PMID- 1455140 TI - [A new form of arbitrary commitment]. PMID- 1455141 TI - [Silicosis and asbestosis. Epidemiology, screening, prevention]. PMID- 1455142 TI - [Chronic otitis. Diagnosis, development, prognosis, principles of treatment]. PMID- 1455143 TI - [Intertrigo. Diagnostic orientation]. PMID- 1455144 TI - [Boutonneuse mediterranean fever. Epidemiology, etiology, diagnosis, treatment]. PMID- 1455145 TI - [Lymphocytosis. Diagnostic orientation]. PMID- 1455146 TI - [Septic, hemorrhagic and cardiogenic shock. Etiology, physiopathology, diagnosis, treatment]. PMID- 1455147 TI - [Hemorrhagic syndrome due to hemostasis disorder]. PMID- 1455148 TI - Atrial natriuretic factor in cats subjected to acute myocardial ischaemia. AB - Eighteen anaesthetized open chest cats were subjected to 10, 30, or 50 min occlusion of the left anterior descending coronary artery (LAD). Heart rate, left ventricular end-diastolic (LVEDP) and systolic pressure (LVSP), and dp/dt were continuously recorded during the experiments. Prior to LAD-occlusion, and just before termination of the experiments, blood samples were collected from the left femoral artery for measurements of atrial natriuretic factor (ANF), catecholamines, electrolytes, urea, and creatinine. Simultaneously, biopsies were collected from the right auricular wall. The tissue was embedded in Lowicryl K4M, and ultrathin sections were incubated with anti-ANF antibodies and secondary antibodies conjugated to gold particles. The density of ANF-containing atrial specific granules labelled with gold particles was morphometrically calculated. LVEDP increased significantly in all three time groups, and when pooling the pre- and postocclusion values, there was an increase from 5.1 +/- 0.4 to 10.3 +/- 1.2 mmHg (p < 0.05). The noradrenaline level increased from 0.93 +/- 0.18 to 2.34 +/- 0.75 nmol l-1 (p < 0.05) after LAD-occlusion. Similarly, the mean plasma level of ANF in the 18 cats increased from 57.6 +/- 11.9 to 98.9 +/- 22.6 pmol l-1 (p < 0.05). Atrial granular density appeared to decline after 10 min of occlusion (from 0.141 +/- 0.017 to 0.127 +/- 0.022 granules-1 microns 2 sarcoplasm), and after 30 min there was a significant decrease (0.080 +/- 0.012 granules/microns 2, p < 0.05). However, after 50 min occlusion the granular density was almost restored (0.133 +/- 0.017 granules/microns 2). Plasma ANF showed a positive linear correlation to LVEDP and to the noradrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455149 TI - Rapid C-reactive protein (CRP) measurements in the diagnosis of acute appendicitis. AB - C-reactive protein (CRP) has been measured in plasma of patients with acute appendicitis and in controls without appendicitis to test the accuracy and diagnostic performance of a new rapid test kit for CRP (NycoCard CRP). The values obtained for CRP by the rapid test correlated well (Rs = 0.92) with the reference method for measuring CRP. The sensitivity, specificity and predictive values were calculated at different cut-off values. At values > 10 mg l-1 a sensitivity of 58% and a negative predictive value of 72% were found. Higher values of sensitivity were observed for men than for women, 69% and 44% respectively. Patients with acute appendicitis who had had symptoms for more than 24 h, had elevated CRP values (cut-off > 10 mg l-1) in more than 80% of cases. Our study shows that the rapid CRP test and the reference CRP test gave an almost identical result. PMID- 1455150 TI - Transcapillary filtration of plasma protein in long-term type 1 (insulin dependent) diabetic patients. AB - To study the pathophysiologic mechanism leading to increased transcapillar sieving of albumin in patients with diabetic nephropathy, subcutaneous interstitial concentrations of albumin, transferrin, total IgG and IgG-4 was measured in 30 long-term type 1 diabetic patients using the skin suction blister method. Eight normal subjects served as controls. The patients were divided in groups according to their urinary albumin excretion: normal (n = 11), micro albuminuria (n = 9), and clinical nephropathy (n = 10). Results were expressed as the blister to serum concentration ratio (Cb:Cs) of each macromolecule. Normoalbuminuric patients had lower Cb:CsIgG ratio than healthy controls (0.28 +/ 0.04 vs. 0.35 +/- 0.09, p = 0.03). The lowest Cb:CsIgG ratio (0.23 +/- 0.07) was found in patients with clinical nephropathy. The same trend could be demonstrated in the other Cb:Cs ratios, but differences there were not significant. No differences related to capillary charge- or size-selectivity could be demonstrated between the groups. The results might reflect an increase of intracapillary hydrostatic pressure or increased capillary hydraulic permeability in the diabetic state per se, augmented during the development of microvascular complications. PMID- 1455151 TI - Serum concentrations and excretion of bile acids in cirrhosis. AB - Bile acid concentrations in serum, and urinary and faecal excretion of bile acids have been studied in ten patients with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, whereas the remaining two patients comprised Child group C. Individual bile acids were isolated and identified by gas chromatography coupled to mass spectrometry. Total fasting serum bile acid concentrations were elevated in all patients, but not correlated to conventional tests of liver function. Eight of the patients had increased urinary excretion of bile acids. Faecal bile acid-excretion was highly variable between patients, and also between Child's group A and C patients. Total fasting serum bile acid concentrations were not correlated to either urinary, faecal, or total bile acid excretion (= synthesis of bile acids) or to the ratio between urinary and faecal excretion of bile acids. The daily synthesis of bile acids showed a large overlap between Child's group A and C patients. The percentage of chenodeoxycholic acid and its metabolites relative to total daily excretion of bile acids did not correlate, indicating that the synthesis pathways for the primary bile acids does not systematically change in relation to the rate of synthesis. We conclude that even in mild cirrhosis, serum bile acid concentrations are elevated. However, no consistent changes in synthesis of bile acids or synthesis pathways was observed in such patients. PMID- 1455152 TI - Biological variation of the leukocyte differential count quantities. AB - The biological variation of the blood concentration and number fraction of the different kinds of leukocytes have been estimated, over a one-year period in a group of 19 women and 20 men, apparently healthy volunteers. All measurements have been performed with a Toa E-5000 haematological analyser. The medians of the within-subject biological coefficients of variation, separated by sex when significant differences exist, are the following for concentrations: 9.4% in men and 15.4% in women for the leukocytes, 16.9% in men and 26.9% in women for the neutrophils, 12.3% for the lymphocytes, 14.9 for the basophils+eosinophils+monocytes (as measured by Toa E-5000); and for number fraction are the following: 8.6% for neutrophils, 0% in men and 7.2% in women for lymphocytes, and 16.7 for basophils+eosinophils+monocytes (as measured by Toa E 5000). With these data the index of individuality, the critical difference for significant change detection and the desirable imprecision have been calculated. PMID- 1455153 TI - Serum hyaluronan and aminoterminal propeptide of type III procollagen: variation with age. AB - The serum levels of hyaluronan and the aminoterminal propeptide of Type III procollagen (PIIINP) were compared in 585 healthy individuals as a function of age. Newborn children displayed high hyaluronan (695 +/- 634 micrograms l-1, mean +/- SD) and PIIINP (295 +/- 152 micrograms l-1) values. The values were not correlated to the gestational week in which the children were born or to the birth weight but there was a significant correlation (p < 0.05) between the hyaluronan and PIIINP levels. During the first year the levels dropped and in childhood (1-16 years of age) both hyaluronan and PIIINP levels were fairly constant at 27 +/- 16 and 22 +/- 8.4 micrograms l-1, respectively. The PIIINP level showed a marked drop in adults compared to children. The drop continued to about 50 years of age (6.5 +/- 2.2 micrograms l-1) and then there was a slight increase in elderly people. The hyaluronan showed a continued increase with age from the level at 16 years of 29 +/- 17 micrograms l-1 to a mean value of 177 +/- 133 micrograms l-1 in people over 75 years. There was no increase in serum hyaluronan in women during pregnancy but the PIINP level increased in the later part of the gestational period. There was no correlation between the serum values of hyaluronan and PIIINP when compared throughout the life span which indicates that the blood levels of the two markers are regulated by independent factors. PMID- 1455154 TI - Myocardial adenine nucleotide depletion within 1 h of acute coronary artery occlusion. AB - In anaesthetized open-chest casts with occlusion of the left anterior descending coronary artery (LAD), adenine nucleotides and degradation products were studied in small myocardial tissue samples (10-20 mg) with high-pressure liquid chromatography, and tissue blood flow was measured with radioactive microspheres 5, 10, 20, 40, and 60 min after LAD occlusion. There was a rapid and parallel decrease of myocardial ATP and accumulation of adenosine, inosine, hypoxanthine, and xanthine both in epicardial and endocardial half-layers of the ischaemic myocardium within the first 20 min of coronary occlusion. After 40 and 60 min, myocardial ATP content decreased and degradation products accumulated further in the endocardium but stabilized epicardially. Analysis of covariance showed that the slightly higher blood flow in ischaemic epicardial layers, did not explain the transmural difference in ATP content after 40 and 60 min. Adenosine decreased after 40 min of ischaemia in both wall layers reaching negligible amounts after 60 min. It is concluded that breakdown of energy stores is less severe in epicardial than in endocardial wall layers during the first hour after acute coronary occlusion in the cat heart. This transmural difference cannot be explained entirely by less severe epicardial ischaemia. Therefore, transmural heterogeneity in metabolic function during severe ischaemia may also be important. PMID- 1455155 TI - Pancreatic beta-cell function evaluated by intravenous glucose and glucagon stimulation. A comparison between insulin and C-peptide to measure insulin secretion. AB - Insulin and C-peptide responses to 0.5 g kg-1 intravenous glucose and 1.0 mg glucagon were studied in 34 healthy subjects (age 19-78 years, mean 45). Fasting blood glucose (r = 0.59; p < 0.001) and glycosylated haemoglobin (r = 0.61; p < 0.001) increased with age, but not the initial C-peptide and insulin responses to the glucose infusion. However, the C-peptide response at 70 min (r = 0.36; p < 0.05), 80 min (r = 0.41; p < 0.05), and 90 min (r = 0.46; p < 0.01) after the glucose infusion correlated with age as well as both insulin (r = 0.42; p < 0.05) and C-peptide (r = 0.45; p < 0.05) responses to the glucagon injection. Reproducibility of insulin and C-peptide responses was evaluated by duplicate tests, separated 2-143 days in time, in 10 healthy subjects (age 19-48 years, mean 32 years) showing no significant differences in median within-subject variation between the initial (1 + 3 min) or overall (0-90 min area under curve) insulin (24% and 17%, respectively) and C-peptide (15% and 14%, respectively) responses to glucose, while the within-subject variation for the fasting values and the response to glucagon was higher (p < 0.05) for insulin (47% and 32%, respectively) than C-peptide (13% and 14%, respectively). Between-subject variation was also lower (p < 0.001) for C-peptide than for insulin. Thus, C peptide measurements in healthy subjects are more reproducible than insulin measurements in determination of beta-cell function. PMID- 1455156 TI - Participation of serum albumin and LDL-cholesterol in impaired blood cell filterability affected by white blood cells in patients with cerebral thrombosis. AB - We examined the effect of white blood cells (WBCs) on the red blood cell (RBC) filterability, and the influence of plasma components on their interaction of their microcirculatory behaviour in cerebral thrombosis patients. Subjects studied were 20 patients with a history of cerebral thrombosis (60 +/- 4.7 years old) (mean +/- SD) and 28 healthy controls (59 +/- 5.4 years old). Filterability indices of RBC suspension (RFI) and suspension with RBCs plus WBCs (RWFI) were measured by the method of Nuclepore filtration. The values of RFI in patients and controls were 0.44 +/- 0.12 and 0.56 +/- 0.16 ml min-1 (mean +/- SD), and RWFIs were 0.33 +/- 0.092 and 0.40 +/- 0.11 ml min-1, respectively. The differences in both of these values between patients and controls were significant (p < or = 0.01 for RFI and p < or = 0.05 for RWFI, based on Student's t test, respectively). Both RFI and RWFI in bed-ridden patients were lower than those in the more active counterparts (p < or = 0.05, based on Student's t test). In patients, RFI and RWFI correlated positively with serum albumin (r = +0.515, p < 0.05; r = +0.533, p < 0.05, based on Student's t test, respectively). The net lowering effect of WBCs on RFI (RFI-RWFI) correlated positively with serum LDL cholesterol in patients (r = +0.574, p < 0.01, based on Student's t test). WBCs play a significant role in reducing RFI, and its effect is related to the pathemas of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455157 TI - Cobalamin binding proteins in human seminal plasma. AB - Transcobalamin (TC) and haptocorrin (HC) are present in normal seminal plasma in substance concentrations ten- to twenty-fold that in blood. The results are given in range and (median). The substance concentration of seminal plasma TC is 3.6 21.9 (8.4) nmol l-1 and of seminal plasma HC 1.4-8.6 (3.0) nmol l-1. Compared to normals the substance concentration of TC is significantly lowered in post vasectomy seminal plasma 2.2-2.9 (5.3) nmol l-1. The Stokes radius and the isoelectric points of seminal plasma TC are identical to TC in blood. PMID- 1455158 TI - Long-term smoking increases transcapillary escape rate of albumin. AB - Transcapillary escape rate of albumin was measured in 11 young and 10 healthy, elderly male subjects. Approximately half of the subjects were chronic cigarette smokers. Transcapillary escape rate of albumin expressed as percentage of decrease in specific activity of plasma albumin per hour averaged 12.3% in long term smokers. This value was significantly elevated and twice as high as values measured in young smokers and in young and elderly non-smokers. It is concluded that capillary permeability to albumin is increased in long-term smokers. Further studies are warranted to examine the pathophysiological mechanism and to what extent this abnormality is reversible. PMID- 1455159 TI - Quantitation of urinary hydroxypyridinium cross-links from collagen by high performance liquid chromatography. AB - Pyridinoline and deoxypyridinoline are intermolecular cross-links in mature collagen in bone and cartilage. The urinary excretion of the two compounds correlates well to bone turnover. A fast, sensitive, and accurate isocratic ion pairing reverse-phase high-performance liquid chromatography method for measurement of pyridinoline and deoxypyridinoline in urine has been established. Intra- and inter-assay precision were 5-7% and 12-14%, respectively. Recovery for pyridinoline was 97.4% and for deoxypyridinoline 94.3%. The detection limit was 0.4 pmol. Pyridinoline:creatinine and deoxypyridinoline: creatinine ratios in healthy subjects, were 38.8 nmol:mmol and 13.0 nmol:mmol, respectively. Increased values of both cross-links were observed in children, in the age group 20-29 in both sexes, and in post-menopausal women. PMID- 1455160 TI - Sensitive enzyme-linked immunosorbent assay for measurement of autoantibodies to human thyroid peroxidase. AB - The development of a sensitive assay for detection of autoantibodies against one of the major thyroid antigens, thyroid peroxidase (TPO), is described. TPO was purified from human thyroid tissue by: (1) isolation of thyroid microsomes using homogenization and differential centrifugation, (2) solubilization of membrane proteins by Zwittergent 3-14, and (3) anion exchange liquid chromatography on a FPLC Mono Q column. Autoantibodies against TPO (TPO-Ab) were measured using an enzyme-linked immunosorbent assay (ELISA) with serum samples diluted 1:100. Standards containing 70, 7, 0.7, 0.02 and 0 U ml-1 TPO-Ab were employed (reference standard code 66/387 NIBSC, London, UK). The detection limit was 0.02 U ml-1 corresponding to 2 U ml-1 in undiluted serum. The inter- and intra-assay coefficients of variation were 8.6% and 5.3%. In 109 healthy control subjects TPO Ab was found in 9 (8.3%), while 43 (97.7%) out of 44 patients with newly diagnosed untreated Graves' disease had detectable TPO-Ab in serum. All of 16 patients with newly diagnosed spontaneously developing primary hypothyroidism had circulating TPO-Ab (range 16-7000 U ml-1). The new assay is a valuable tool for evaluation of thyroid autoimmunity in individual patients and for studying the epidemiology of thyroid autoimmunity. PMID- 1455161 TI - Effect of lovastatin on lipoprotein fluidity in patients with hypercholesterolaemia. AB - Lovastatin was administered to six hypercholesterolaemic patients (mean plasma cholesterol 450 mg dl-1). Plasma lipoproteins (VLDL, LDL, and HDL) were separated before and following 7 and 12 weeks treatment with lovastatin. Fluidity was quantified by fluorescence polarization measurements using 1,6-diphenyl 1,3,5 hexatriene (DPH) as the fluorescent probe. Lovastatin treatment resulted in a significant reduction of total plasma cholesterol, LDL cholesterol and VLDL cholesterol (-41%, -44%, -68%, respectively). Fluidity measurements showed significant (p < 0.01) increase in LDL fluidity by 11% and 21% after 7 and 12 weeks of lovastatin treatment, whereas, VLDL fluidity was increased by 27% after 12 weeks of therapy. HDL fluidity was not altered. These alterations in the fluidity of the atherogenic lipoproteins (LDL and VLDL) in hypercholesterolaemic patients may prove to be of significance in reducing the risk of atherosclerosis. PMID- 1455162 TI - Transferability of clinical laboratory data within a health care region. AB - Analytical data for S-Creatinine and S-Urate are presented from seventeen laboratories in the Swedish Uppsala-Orebro regional quality assessment program. The bias and imprecision as well as the instability of the measurement procedures in the participating laboratories were estimated over three 14-week periods. Bias was estimated by a linear least squares fit of the difference between measured and assigned values vs. assigned values, and expressed in absolute and relative terms. Instability of the measurement procedures was estimated by comparing slope and intercept of regression lines of measured vs. assigned values from three fourteen week periods. According to our experiences we recommend regression analysis to describe the performance of the analytical methods of a laboratory over time. The results show that most laboratories fell within the limits of +/- 15% bias for S-Creatinine above 100 mumol l-1 and +/- 17% for S-Urate at concentrations above 250 mumol l-1. Various steps to reduce the inter-laboratory variability are suggested, including numerical correction of individual laboratory results using correction functions. In a few laboratories, instability was too high to allow for numerical corrections of analytical results. PMID- 1455163 TI - Renal function in patients with untreated acute myocardial infarction. AB - This study provides data on plasma volume (PV), extracellular volume (ECV) and renal function in 8 untreated patients with acute myocardial infarction (AMI). At day 2 and day 10 after AMI, glomerular filtration rate (GFR), urinary excretion rate of water (Vu), sodium clearance (CNa) and lithium clearance (CLi) were used for assessing reabsorption rates of sodium and water in proximal and distal nephron segments. PV and blood pressure at day 2 were not significantly different from values at day 10. Heart rate (HR), weight and ECV at day 2 were significantly increased when compared with values at day 10 (78 vs. 62 pr. min and 17.0 vs. 16.2 1, respectively). Plasma norepinephrine values were slightly elevated at day 2 and day 10. GFR was initially high and decreased from day 2 to day 10 (118 vs. 104 ml min-1) together with CLi and Ck. However, Vu, CNa and fractional excretion rate of sodium increased markedly from day 2 to day 10. The results suggest that sodium and water retention in the initial phase of AMI without left ventricular failure is due to an increase in tubular reabsorption in distal nephron segments mediated by mechanisms other than the sympathetic nervous system. PMID- 1455164 TI - DNA synthesis and related enzymes altered in compensatory lung growth in rats. AB - Left pneumonectomy was performed on 4 week-old male Fischer-344 rats. Changes in DNA biosynthesis and the activities of related enzymes were studied in the contralateral lungs of the pneumonectomized animals (n = 55) and compared with sham-operated (n = 55) and untreated control animals (n = 40) The wet weight of the contralateral lung of the pneumonectomized rats reached that of both lungs of the untreated and sham-operated rats 14 days after the operation. The activities of thymidine kinase and DNA polymerase from the regenerating lungs were elevated on Days 1 and 7. To determine the molecular forms of DNA polymerase in the crude extract, phosphocellulose column chromatography was performed. The type of DNA polymerase with the highest activity was alpha in regenerating lung on Days 1, 3, and 7. These results suggest that DNA replication for cellular proliferation was elevated in the remaining lung after pneumonectomy. In addition, an interlobar difference in DNA biosynthesis was observed in the remaining lung. The increase was especially marked in the cardiac lobe, followed by increases in the DNA content of the remaining lobes on Day 7. From these observations we conclude (1) that increased activity of DNA polymerase alpha is likely to be an initial change in compensatory lung growth, and may be caused by some unknown stimulator in lung tissue, and (2) that DNA biosynthesis may differ among the lobes of the lung, at least until 3 days post-pneumonectomy. PMID- 1455165 TI - Enzymatic microdetermination of plasma and serum free fatty acids. AB - A simple and sensitive enzymatic method for determination of plasma and serum fatty acids (FAs) is described. The method is based on acylation of long chain FAs by a bacterial acyl-CoA synthetase (ACS) producing equivalent amounts of acyl CoA and AMP. AMP production was measured using the coupled reaction of myokinase (MK), pyruvate kinase (PK) and lactate dehydrogenase (LDH) allowing fluorinate detection of NADH. Two moles of NAD were produced per mole of FA acylated. Concentrations of substrates and enzymes were kept as low as possible maintaining the ACS reaction as rate limiting. Addition of fat-free human serum albumin (HSA) to standards reduced initial reaction rates but did not affect end-point fluorescence levels. Triton X-100 partly counteracted the inhibition by HSA. To keep albumin concentration low, plasma or serum samples were diluted by 1:400. Duplicate measurements of plasma or serum FA concentrations between 0 and 2 mmol l-1 can then be performed on 5 microliters samples with intra- and inter-assay variation coefficients of 1.7 and 4% respectively. PMID- 1455166 TI - Taurine content and distribution in equine skeletal muscle. AB - Taurine (TAU) is found in large but variable amounts in the skeletal muscles of many species. It has been reported that slow twitch muscles in the rat exhibit higher TAU levels than fast twitch muscles. Variation in muscle taurine content may be attributable to differences in the fibre type composition of different muscles. TAU content (mmol kg-1 dry muscle) and percentage type-1, type-2A, and type-2B fibre section area (f.s.a.) were measured in muscle samples taken from up to six sites in the middle gluteal muscle of four horses and one pony at post mortem and in biopsy samples taken from twenty Thoroughbred horses in race training. TAU was positively correlated to type-1 f.s.a. (r = 0.94, p < 0.001) in both post mortem samples and biopsies from horses in race-training. Multiple linear regression analysis was used to estimate the TAU content of individual fibre types when present at 100%. TAU is almost exclusively localized in type-1 fibres. The TAU content of type-1 and type-2A fibres was estimated to be 45.4 mmol kg-1 d.m. and 4.5 mmol kg-1 d.m. respectively in the post mortem horses, and 32.4 mmol kg-1 d.m. and 7.9 mmol kg-1 d.m. respectively in the horses in training. TAU was estimated to be absent from type-2B fibres in both horse groups. PMID- 1455167 TI - Influence of acid-secretion blockers on gastric and hepatic alcohol dehydrogenase in rat. AB - The effects of Cimetidine, Ranitidine, and Omeprazole on gastric and hepatic alcohol-dehydrogenase (ADH) activity was studied in rat. Two apparent values for Km were found for gastric ADH (220 mmol l-1 and 1043 mmol l-1 respectively) and one for hepatic ADH (0.54 mmol l-1). Cimetidine was shown to exert an uncompetitive inhibition of low Km gastric ADH with a Ki of 0.167 mmol l-1 and a competitive inhibition of high Km gastric ADH with a Ki 2.3 mmol l-1. Ranitidine was found to present non-competitive inhibition only on low Km gastric ADH with a Ki of 12 mmol l-1. Omeprazole affects only low Km gastric ADH with a Ki of 5.6 mmol l-1 and presents a linear-mixed type of inhibition. Hepatic ADH was shown to be competitively inhibited only by Cimetidine with a Ki of 6.0 mmol l-1 whereas no inhibition for either Ranitidine and Omeprazole was observed. These results confirm the inhibitory action of Cimetidine on both gastric and hepatic ADH; Ranitidine and Omeprazole show minor effects on ADHS activity and probably on first-pass metabolism. PMID- 1455168 TI - Phorbol myristate acetate-induced lung injury: involvement of reactive oxygen species. AB - Using lucigenin-enhanced chemiluminescence, isolated rat lungs perfused with physiological salt-Ficoll solution were studied to test whether phorbol myristate acetate (PMA)-induced lung injury was mediated by reactive oxygen species (ROS). PMA (0.03 micrograms ml-1) caused small but significant increases in lung ROS levels and pulmonary arterial perfusion pressure (Ppa) but did not induce lung oedema. PMA (0.15 micrograms ml-1) induced lung oedema with large increases in ROS production and Ppa. Superoxide dismutase (SOD) inhibited the increases in ROS, Ppa, and lung oedema. Catalase and dimethylthiourea inhibited lung oedema but did not attenuate the increases in ROS and Ppa entirely. Indomethacin attenuated lung oedema partially but did not inhibit the increases in ROS and Ppa. These data indicate that PMA-induced lung injury is dependent on PMA concentration and ROS are responsible for such lung injury. Thromboxane plays a minor role for PMA-induced lung injury. The different effects of oxygen radical scavengers suggest that different radical species contribute to the increased pulmonary vascular response and lung injury. PMID- 1455169 TI - Mononuclear cell magnesium and retention of magnesium after intravenous loading in patients with acute myocardial infarction. AB - A magnesium (Mg++) retention test was performed in 19 patients with acute myocardial infarction (AMI) 4-11 days after admission to the coronary care unit. The retention of Mg++ was 45 +/- 23% of the 30 mmol given intravenously. It has been proposed that a retention of more than 20% represents Mg++ deficiency. The mononuclear cell Mg++ concentration before the retention test was on an average slightly higher in the AMI patients than in 25 healthy volunteers (72.5 +/- 24.2 vs. 62.9 +/- 9.2 mumol g-1 protein) indicating no Mg++ depletion in the first group. The reason why patients during the phase of AMI show an increased retention of Mg++ is unknown, but changes in concentrations of several hormones and a reduction in blood glucose could be of importance. Serum concentrations of Mg++ were lower on admission than after 4-11 days. These initial reductions are probably due to increased concentrations of circulating catecholamines during the early hours of AMI. PMID- 1455170 TI - Interferences by cryoglobulins and cold agglutinins with blood cell measurement on coulter counter. PMID- 1455171 TI - Comparative study of alkaline phosphatase in human and animal samples using methods based on AMP and DEA buffers: effects on quality control. PMID- 1455172 TI - The aspartic proteases. In honour of the retirement of Professor Bent Foltmann. Danish Biochemical Society meeting. Copenhagen, 27 May 1992. PMID- 1455173 TI - Genetic variation of human aspartic proteinases. AB - The human aspartic proteinases include pepsinogen A, pepsinogen C, cathepsin D, cathepsin E and renin. Comparative analysis of the proteinase genes reveals a high degree of similarity with regard to their respective coding sequences and the location of exon-intron junctions. Despite strong conservation of the regions containing the active site aspartyl groups, genetic polymorphisms have been identified for each of the proteinase genes with the exception of cathepsin D. These genetic polymorphisms are useful for localization of genes on linkage maps as well as determination of gene copy number. The chromosomal location of each aspartyl proteinase has been determined by a variety of gene mapping methods employing recombinant DNA probes including; analysis of somatic cell hybrid mapping panels, in situ hybridization to metaphase chromosome preparations and family linkage analysis with polymorphic markers. Pepsinogen A exhibits the most extensive polymorphism among aspartic proteinases which can be detected by either by protein electrophoresis or by DNA analysis. Southern blot hybridization with respective DNA probes and polymerase chain reaction (PCR) amplification have revealed nucleotide differences located within the coding and noncoding portions of the aspartic proteinase genes. These polymorphisms can be used to investigate potential roles of each proteinase in genetically influenced clinical conditions. The development of additional highly polymorphic markers detected by PCR amplification of divergent nucleotide sequence repeats will greatly assist with documentation of the effect of genetic variation of the aspartic proteinases may have in specific clinical diseases such as ulcer and hypertension. PMID- 1455174 TI - Chicken pepsin and the other avian aspartic proteinases. AB - The results of studies on chicken pepsinogen and pepsin from the adult animals and from chicken embryos are presented and some of the problems are discussed. A brief summary of other investigations on aspartic and acid proteinases of birds is given and the possible future trends of research in this field are outlined. PMID- 1455175 TI - Understanding HIV protease: can it be translated into effective therapy against AIDS? AB - The protease of human immunodeficiency virus (HIV) has been extensively studied. The structure and function relationships of this protease and its role in HIV life cycle is well known. We have use recombinant HIV protease and mutagenesis technology to study HIV protease and compare it to the eukaryotic aspartic proteases. When putative active-site hydrogen bonds are placed in the HIV protease, the pKa values of two active-site groups are only slightly downshifted. Corresponding removal of these H-bonds from the active sites of pepsin and rhizopuspepsin do not appreciably alter the active-site pKa values. The Kcat values are strongly decreased by these mutations. These observations suggest that the active-site H-bonds in HIV protease and other aspartic proteases control the rigidity of the catalytic apparatus but not the ionization of the active-site groups. A mechanism of catalysis by the HIV protease has been suggested based on kinetic and mutagenesis studies. The strategies involved in the development of HIV protease inhibitors are discussed. In spite of the pitfalls in each approach, it appears probable that a battery of inhibitors can be developed for the treatment of AIDS. PMID- 1455176 TI - Substrate specificity and inhibitors of aspartic proteinases. AB - Aspartic proteinases of vertebrate, fungal and retroviral origin have been characterised by utilisation of chromogenic peptide substrates and synthetic inhibitors as probes. By this means, the molecular topography of sub-sites within the active site cleft of individual enzymes has been elucidated. With suitable selection of residues to occupy each sub-site, the design of effective inhibitors specifically targetted against individual aspartic proteinases has become feasible. PMID- 1455177 TI - Some aspects of structural studies on aspartic proteinases. AB - This paper gives a brief overview over the differences and similarities in the structure of aspartic proteinases presently available. Comparison of the three dimentional structure of different aspartic proteinases by a common intramolecular coordinate system have been performed. The intramolecular movable subdomains have been localized and the role of motion in substrate binding and zymogen activation is discussed. PMID- 1455178 TI - Multidisciplinary cycles for protein engineering: site-directed mutagenesis and X ray structural studies of aspartic proteinases. AB - The specificity and pH profile of aspartic proteinases have evolved to include not only pepsin with a broad specificity and an optimal activity in acid media, but also renin, with high specificity for angiotensinogen and activity close to neutral pH. Comparisons of the structures and catalytic activities of aspartic proteinases provide helpful clues for engineering new activity profiles. We illustrate an approach that involves recombinant DNA techniques, biochemistry, structure determination and biocomputing. We use the 3-D structures of inhibitor complexes of several aspartic proteinases to define likely intermediates and specificity sub-sites. The multidisciplinary research is organised as cycles, in which each cycle tests a design hypothesis proposed in the previous cycle. We use one member of the aspartic proteinase family, chymosin, to illustrate these ideas in engineering enzymes with altered pH optima and specificities. PMID- 1455179 TI - The aspartic proteases. AB - The Aspartic proteases (EC 3.4.23) are a group of proteolytic enzymes that share the same catalytic apparatus. Members of the aspartic protease family can be found in different organisms, ranging from humans to plants and retroviruses. The best known sources of aspartic proteases are the stomach of mammals, yeast and fungi, with porcine pepsin as the proto type. The aim of this review is to summarize some of the characteristics of the aspartic protease family. PMID- 1455180 TI - Protein engineering of the milk-clotting aspartic proteinases. AB - Calf Chymosin and a fungal protease from Mucor pusillus (Mucor rennin) are members of the aspartic proteinases used as milk-coagulants in cheese industry. A system for production of recombinant chymosin as inclusion bodies in Escherichia coli cells and its refolding into the active form was established. Another expression system for production of Mucor rennin in Saccharomyces cerevisiae was also established. Mucor rennin was efficiently excreted from the yeast host as a heavily glycosylated form. Glycosylation affected both the secretion and the enzyme properties. Site-directed mutagenesis of the Tyr residue at position 75 in chymosin and Mucor rennin revealed its crucial role in catalytic function of the aspartic proteinases. The results also suggested possibility to improve practical properties of the milk-clotting enzymes by site-directed mutagenesis. PMID- 1455181 TI - Production of prochymosin, pepsinogen and progastricsin, and their cellular and intracellular localization in bovine abomasal mucosa. AB - A brief overview of research is presented on the production, cellular and intracellular localization of prochymosin, pepsinogen and progastricsin in bovine abomasal mucosa from fetus to adult. Prochymosin is produced early during gestation (10th week) and is significantly related to milk-feeding. Pepsinogen and progastricsin start to be produced later during gestation (20th week) and are produced in low amounts as long as the calf is fed milk. With age, pepsinogen becomes the dominating zymogen in the abomasal mucosa. Most of the cell types in the fundic gland have the ability to produce all three zymogens and are also found in the same individual secretory granules of these cells. PMID- 1455182 TI - Chymosin: a short review on foetal and neonatal gastric proteases. AB - All vertebrates in which the age dependent expression of gastric proteases has been investigated show a characteristic developmental pattern. Neonatal proteases which show partial immunochemical identity with calf chymosin have been observed in several species. The amino acid sequence of lamb chymosin shows 94% of identity with that of calf chymosin. Chymosins from pig and cat show about 85% and 75% of identity with calf chymosin. Chicken embryonic pepsinogen appears to be more related to calf chymosin than to other gastric proteases. A pseudo-gene for a chymosin-like protease from man has been identified. But a functional, human chymosin-like neonatal protease has not been identified. The possible physiological significance of chymosin and the clotting of milk are discussed. PMID- 1455183 TI - Clinical implications of serum pepsinogen and progastricsin in man. AB - The serum pepsinogens in man have been reviewed with respect to clinical and physiological significance. The many places of synthesis of pepsinogen (PG A) and progastricsin (PG C) are described. The major part of serum pepsinogen and progastricsin is synthezized in the stomach, and the findings after antrectomy indicate that the majority of the pepsinogens in serum originates from the corpus of the stomach. The concentrations of pepsinogen and progastricsin in serum in relation to stomach diseases, e.g. ulcer disease, gastritis, and cancer of the stomach, are described. Despite typical findings, i.e. hyperpepsinogenemia in duodenal ulcer disease, or hypopepsinogenemia in atrophic gastritis or stomach cancer, there is a big overlap in serum concentrations between the groups reducing the clinical value of routine measurements of pepsinogens. Most promising are the findings in stomach cancer disease, where the combined measurement of pepsinogen levels and the isozymogen Pg5 is found to be highly indicative for the presence of a gastric carcinoma. Reports state that pepsinogens are excellent markers of recurrence of gastric cancer somewhere in the body after total gastrectomy. Genetical studies have--concerning pepsinogen- proved the multiple gene/multiple loci model. There is only a single progastricsin gene in humans and no genetic heterogenity has been found. Finally, the relationship between gastric infection with the bacterium Helicobacter pylori, and elevated pepsinogen and progastricsin levels in the blood, and the search for serologic markers of gastric diseases is discussed. PMID- 1455184 TI - Gene structures of pepsinogens A and C. AB - Pepsinogen is an inactive precursor of pepsin, a typical aspartic proteinases, synthesized in the chief cells of gastric glands. There are two major groups of pepsinogen, namely pepsinogen A (PGA) and pepsinogen C (PGC) (or progastricsin), and each frequently has isozymogens. The relative extents of expression of the two pepsinogens vary among animal species and, moreover, their biosynthesis is known to be affected by such bioactive peptides as gastrin and secretin; however, the regulation mechanism of pepsinogen biosynthesis, hence pepsinogen gene expression is not yet clear. Therefore, it is thought to be of fundamental importance to elucidate the primary structures of the pepsinogen gene for such studies. This report describes the primary structures of human PGA and PGC genes and rat PGC gene. The organization of the genes is essentially the same; each gene was found to be separated into nine exons by eight introns of various lengths, encoding the amino acid sequence of the corresponding prepepsinogen. These results show that these genes are all derived from a common ancestral gene. The 5'-flanking region of human PGA gene, however, was different from those of human and rat PGC genes, whereas those of human and rat PGC genes were similar to each other. Thus, it is suggested that the expression of the PGA and PGC genes are somewhat differently regulated. PMID- 1455185 TI - Cytokines in inflammatory bowel disease. PMID- 1455186 TI - Effects of interferon-gamma and tumour necrosis factor-alpha on epithelial HLA class-II expression on jejunal mucosal biopsy specimens cultured in vitro. AB - HLA class-II molecules present antigen to the immune system and are expressed by normal villous enterocytes. Increased expression occurs in inflammatory bowel and coeliac disease, and it is suggested that cytokines may mediate such increased expression. The effects of the cytokines IFN-gamma and TNF-alpha on epithelial HLA class-II expressions have been studied in adult human jejunal mucosal biopsy specimens cultured in vitro. Specimens from nine patients with normal jejunal histology were cultured for 24 h with IFN-gamma, TNF-alpha, or both. Six of nine patients showed increased HLA-DR and HLA-DP expression after culture with the cytokines. We have demonstrated that these cytokines induce increased epithelial HLA class-II expression in adult jejunal mucosal specimens cultured in vitro, a model that most closely resembles the in vivo state. This provides further evidence that such increased expression occurs secondarily to the products of immunologic activation. PMID- 1455187 TI - Gastric changes in coronary-operated patients with low-dose aspirin. AB - Low-dose aspirin is widely used in patients operated on for coronary disease as secondary prevention of coronary artery occlusion. The changes caused by aspirin in therapeutic doses to gastric mucosa are well documented, but the effect of long-term low-dose aspirin is not so well known. Forty-six volunteer coronary operated patients with daily low-dose aspirin were interviewed postoperatively, and an upper gastrointestinal tract endoscopy was performed and biopsy specimens taken 3 months after the operation. The findings were compared with a normal population sample of 358 persons from a study previously published. There were significantly more erosions and ulcers or fresh scars in the study group than in the control population--11 of 46 patients and 24 of 358 patients, respectively. The presence of superficial gastritis was similar. Mostly, the lesions were asymptomatic. History of peptic ulcer disease, use of other ulcerogenic drugs, smoking, and alcohol consumption had no predictive value for acute lesions. In contrast, the lesions were associated with chronic superficial gastritis and Helicobacter pylori infection. PMID- 1455188 TI - Influence of stress on the healing and relapse of duodenal ulcers. A prospective, multicenter trial of 2109 patients with recurrent duodenal ulceration treated with ranitidine. RUDER Study Group. AB - The influence of psychologic factors on the healing and relapse of duodenal ulcers under treatment with ranitidine was studied in a prospective, multicenter trial in 2109 patients with an endoscopically proven duodenal ulcer (DU) and a history of recurrent duodenal ulceration. All patient received ranitidine (300 mg daily), and, after healing, 1899 patients continued maintenance treatment (ranitidine, 150 mg daily) for 2 years. A physician's assessment of stress (stress or no stress) was made at every consultation. In the healing phase an overall classification of stress as absent, intermittent, or continuous was made, and in the maintenance phase patients were classified dichotomously as having stress (stress on at least half of the follow-up consultations) or no stress. In addition, at the start of the healing phase stress was measured by means of a standardized questionnaire. Continuous stress, as assessed by the physicians, was associated with a lower 14-day healing rate (35.7%) than intermittent or absent stress (42.4%; relative risk (RR) for delayed healing in patients with continuous stress, 1.19; 95% confidence interval (CI), 1.06-1.33; P < 0.02). Differences in the 14-day healing rate for patients with low and moderate stress scores (43.1%) compared with those with high and very high stress scores (37.9%) just failed to reach statistical significance (RR for patients with stress, 1.14; 95% CI, 0.998 1.29; P = 0.051). During the 1st year of maintenance treatment 18.3% of patients with stress, but 10.9% of patients without stress, had a DU relapse (RR of stress for DU relapse during the first year, 1.73; 95 CI, 1.44-2.09; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455189 TI - Can pH recordings suggest defective esophageal peristalsis in patients with gastroesophageal reflux? AB - The data provided by 24-h pH monitoring in 40 patients with gastroesophageal reflux, divided in three groups in accordance with esophageal motor pattern, were compared. Patients with hypomotility had significantly greater reflux rates than those with normal motility or hypermotility, if we consider both total time with pH < 4 and time with pH < 4 corresponding to episodes of > 5 min duration. We conclude that when 24-h pH monitoring shows very high reflux rates, basically corresponding to episodes lasting > 5 min, we should suspect the presence of defective esophageal peristalsis, which must be confirmed with a manometric study. PMID- 1455190 TI - Observer homogeneity in the histologic diagnosis of Helicobacter pylori. Latent class analysis, kappa coefficient, and repeat frequency. AB - Four pathologists independently examined 82 antral mucosal biopsy specimens for the presence of Helicobacter pylori and indicated whether their assessments were certain. The pathologists made a positive diagnosis in from 56% to 84% of the specimens (significant heterogeneity, p < 0.01). The frequency of uncertain diagnoses was from 4% to 20% (p < 0.01). Uncertain statements occurred more frequently among negative than among positive diagnoses. For the six pairs of observers the kappa coefficients were between 0.39 and 0.82. By a latent class analysis measures of diagnostic accuracy were calculated comparing the observers' assessments with an estimated consensus diagnosis. The predictive values of a positive diagnosis ranged from 0.70 to 1.00. By calculation of repeat frequencies -that is, the probability that an observer's statement was confirmed by another observer--it became evident that uncertain statements were less frequently (61%) confirmed than were certain ones (85%). It is concluded that observer homogeneity is only moderate with regard to the histologic diagnosis of H. pylori, which should be considered both in daily clinical routine and in scientific studies. Disagreement between observers was associated with negative diagnoses, presumably because the pathologists felt more uncertain in these cases. PMID- 1455191 TI - Symptom provocation in irritable bowel syndrome. Effects of differing doses of fructose-sorbitol. AB - The role of fructose and sorbitol, when ingested together, in the aetiology of irritable bowel syndrome (IBS) is controversial. The aims of this study in IBS patients, therefore, were to compare differences in symptom provocation with various doses of fructose-sorbitol and to relate differences in the extent of colonic hydrogen production after each dose to such symptom provocation. Two different mixtures of fructose and sorbitol--20 g fructose plus 3.5 g sorbitol ('lower' dose) and 25 g fructose plus 5 g sorbitol ('higher' dose)--were administered to 15 patients with IBS and to 24 healthy controls. Breath hydrogen concentrations were determined at 10-min intervals for 3 h after ingestion of each mixture, and the presence and severity of a range of gastrointestinal symptoms were recorded on a standard form before, during, and after the study. Total symptom score in IBS patients, but not controls, was greater (p < 0.05) after the higher than after the lower dose of fructose-sorbitol mixture, and, for the higher dose, symptoms were significantly greater in IBS patients than in controls (p < 0.05). Moreover, the increase in total symptom score between the higher and lower dose mixtures was of a greater magnitude (p = 0.01) in IBS patients than in controls. No significant correlation was observed between the increase in symptom score and the increase in peak hydrogen concentration or the increase in integrated hydrogen response between lower and higher dose mixtures, although these latter increases were at times substantial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455192 TI - Ulcerative proctocolitis in Orebro, Sweden. A retrospective epidemiologic study, 1963-1987. AB - In a retrospective epidemiologic study of the period 1963 to 1987 the annual incidence of definite ulcerative proctocolitis increased from 3.3 to 14.9/10(5), and during the last 10 years the mean incidence was 13.1/10(5) population. The incidence of extensive and total colitis was fairly stable, whereas an increase of ulcerative proctitis and distal colitis was seen. The increase in incidence is probably an artefact caused by better retrieval of cases in the latter part of the study. The prevalence on 31 December 1987 was 234/10(5) inhabitants. The male to female ratio was 1.59:1, compared with 0.96:1 in the general population. The median age at diagnosis was 33 years and increased almost 7 years by the end of the study, probably caused by an increased proportion of ex-smokers, who at diagnosis were, on average, 9 years older than lifetime non-smokers. The highest age- and sex-specific incidence was found in middle-aged men, who were ex-smokers to a significantly higher extent than women. No specific birth cohort was at an increased risk, and no second incidence peak in older age groups was seen. PMID- 1455193 TI - No significant correlation between histologic changes of the papilla of Vater and juxtapapillary diverticulum. Special reference to the pathogenesis of gallstones. AB - The aim of this study was to investigate the significance of histologic changes of the papilla of Vater in cases with a juxtapapillary diverticulum, with special reference to the pathogenesis of gallstones. Three hundred and sixty-two autopsy cases, mainly of aged people, were analyzed. The incidence of both diverticulum and gallstone increased with age. The presence of diverticulum was associated with a significant increase of gallstones (49% versus 20%; P < 0.01). Analysis by the type of gallstones showed a significantly higher incidence of bilirubinate in cases with juxtapapillary diverticula. Stones both in the gallbladder and in the extrahepatic bile ducts were more prevalent in cases with diverticula as compared with the cases without diverticula. No significant relationship was found between juxtapapillary diverticula and the degree of histologic changes in the papilla of Vater, such as inflammatory cellular infiltration, fibrous proliferation, glandular proliferation, or muscular hypertrophy and proliferation of the sphincter of Oddi. These facts imply that juxtapapillary diverticula are not involved in the formation of gallstones via histologic changes of the papilla of Vater, whereas diverticula may play an important role in the pathogenesis of gallstones, especially of bilirubin stones. PMID- 1455194 TI - Free protein S deficiency in patients with chronic inflammatory bowel disease. AB - Free protein S, protein C, and C4b-binding protein (C4b-BP) were measured in randomly selected outpatients: 22 with Crohn's disease (CD) and 16 with ulcerative colitis (UC). Active disease was recorded in 10 patients with CD and 4 with UC. Fourteen patients (63.6%) with CD and 4 (25%) with UC had free protein S values below the normal range, with mean values of 62% and 78% of that found in healthy control subjects (p < 0.01). The C4b-BP level was 127% in patients with CD as compared with 89% in both healthy subjects and UC patients (p < 0.01). The protein C levels were similar in the three groups. The present results add to the factors already known favouring thromboembolic complications in inflammatory bowel disease and which might play a major role both for the pathogenesis and for the increased tendency to venous thromboembolism in these diseases. PMID- 1455195 TI - Cyclosporin pharmacokinetics after intravenous and oral administration in patients with Crohn's disease. AB - Cyclosporin kinetics were estimated after single-dose intravenous and oral administration in 12 patients with Crohn's disease in accordance with a three compartment model with zero-order inputs. Cyclosporin was measured in whole blood with a specific monoclonal radioimmunoassay. The median bioavailability (f) was 23.7% (range, 0-49.1%); the distribution volume at steady state, 2.3 l/kg (range, 1.0-3.5 l/kg); clearance (CL), 7.6 ml/min/kg (range, 4.8-10.8 ml/min/kg); and t1/2(z) 7.9 h (range, 3.2-13.9 h). Both the extent and rate of bioavailability were significantly lower in six of the patients, who had low or undetectable cyclosporin levels during a preceding therapeutic trial. After repeated oral administration significant correlations were found between the single-dose f/CL ratios and the steady-state blood concentrations, indicating that the kinetics did not change markedly with time. We conclude that the disposition kinetics of cyclosporin in patients with Crohn's disease are comparable to those of other groups, whereas the bioavailability may be decreased. It is suggested that cyclosporin levels should be monitored closely, and intravenous treatment should be considered in patients with a rapid gut transit time, because cyclosporin absorption seems to follow zero-order kinetics. PMID- 1455196 TI - Effect of drugs on colonic eicosanoid accumulation in active ulcerative colitis. AB - The effect of immunosuppressive drugs, 4-aminosalicylic acid (4-ASA), acetyl 5 aminosalicylic acid (5-ASA), and ketotifen on human colonic eicosanoid accumulation was evaluated in view of enhanced accumulation in patients with active ulcerative colitis. Azathioprine (100 micrograms/ml), cyclosporin (100 micrograms/ml), and methotrexate (100 micrograms/ml) significantly inhibited, by 25-35%, prostaglandin E2 (PGE2) accumulation by organ-cultured colonic mucosa of ulcerative colitis patients. Methotrexate was the only immunosuppressive drug that inhibited leukotriene B4 (LTB4) accumulation (50%), whereas azathioprine inhibited the accumulation of leukotriene C4 (LTC4) (25%). 5-ASA and its metabolite, acetyl 5-ASA, inhibited by 20-70% PGE2, LTB4, and LTC4 accumulation in the culture, supporting the contention that acetyl 5-ASA is as active as 5-ASA in these respects. 4-ASA had no effect on any of the eicosanoids. Ketotifen, a mast cell stabilizer, significantly inhibited the accumulation of PGE2, LTB4, and LTC4 by 33-60%. These results suggest a potential, new, unrecognized mode by which the immunomodulators induce part of their therapeutic effects in inflammatory bowel disease and support the contention that acetyl 5-ASA is as active as 5-ASA. The results obtained also indicate that ketotifen, used effectively in the prevention of bronchial asthma, inhibits the accumulation of colonic eicosanoids and, thus, may be of value in the treatment of inflammatory bowel disease. PMID- 1455197 TI - Triple therapy of Helicobacter pylori infection in peptic ulcer. A 12-month follow-up study of 93 patients. AB - This study was undertaken to evaluate the success of triple therapy in peptic ulcer patients and ulcer relapses. One hundred and one consecutive Helicobacter pylori-positive peptic ulcer patients were assigned to an open trial with 2 weeks of treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. At the 6-week follow-up only 1 duodenal ulcer was unhealed of 57 active ulcers, and H. pylori was found to be eradicated in 84% of the 100 subjects. The sensitivity to metronidazole was determined from 71 pretreatment strains of H. pylori. Eradication of H. pylori succeeded in 89% of the patients with metronidazole-susceptible strains and in 61% of patients with metronidazole resistant strains (p < 0.03). All 16 patients in whom the treatment failed to eradicate the organism had metronidazole-resistant strains after treatment. The ulcer relapse rate was low. At the 12-month follow-up of 93 patients only 1 of the 84 H. pylori-negative patients (including 4 patients after new successful therapy) had relapsing ulcers (2 asymptomatic episodes), and 1 had H. pylori reinfection, whereas 3 of the 9 bacteria-positive patients relapsed (p = 0.002); at the 2-year control 2 more patients had ulcer relapses. The eradication of H. pylori infection clearly prevents relapses of peptide ulcer, but the success of triple therapy depends on the frequency of pretreatment metronidazole-resistant H. pylori strains. PMID- 1455198 TI - Biometric evaluation of gastric urease activity in man. AB - The 14C-urea breath test is claimed to be the best test for detection of Helicobacter pylori infection. We present a procedure for estimating its cutoff value on the basis of biometric evaluation only, without involving other diagnostic methods. Cumulative gastric urease activity (CA) was determined during the first 30 min after oral administration of 14C-urea (92.5 kBq) in 56 random volunteers and 49 consecutive patients with peptic ulcer disease. The distribution of CA in random volunteers was positively skewed. Logarithmic transformation yielded two separate populations, each normally distributed. Their normal probability density functions intercepted at log cutoff value. A bimodal distribution of log CA was confirmed in patients with peptic ulcer disease before and after treatment aimed at H. pylori eradication. Cutoff values were determined for both random volunteers and patients with peptic ulcer disease. By application of the present procedure for determination of cutoff value, the 14C-urea breath test distinguishes between individuals who have an increased gastric urease activity and individuals who do not, with the smallest possible arbitrariness. PMID- 1455199 TI - Prediction of major pathologic conditions in dyspeptic patients referred for endoscopy. A prospective validation study of a scoring system. AB - This study aimed to validate the use of a decision support system previously developed on answers to a structured interview of dyspeptic outpatients and designed to identify patients at low risk of organic dyspepsia. We evaluated the performance of the scoring system in two cohorts of dyspeptic outpatients: 878 consecutive Danish patients (study group) referred for upper endoscopy and 1279 British patients whose results had previously been reported (validation group). Performance of the scoring system was analysed by receiver-operating characteristic (ROC) curves and comparison of loss in detection rate of organic dyspepsia, defined as cancer, ulcer, and complicated oesophagitis. The performance of the scoring system in the study group was less favourable over the entire span of cut-off points evaluated. This was reflected by a significant decrease in area under the ROC curve (65.1% versus 75.0%). The only cut-off point with an acceptable loss in detection rate (3.1%) led to a reduction in endoscopic activity of only 7.5%. Despite optimal working conditions the scoring system could not be used as a safe method of extracting dyspeptic patients with a low probability of organic dyspepsia. Before adopting a predictive scoring system, clinicians must evaluate its applicability in their own setting. PMID- 1455200 TI - [Europe and the Swiss dental profession]. PMID- 1455201 TI - [The basic ideas for evaluating diagnostic tests in medicine and periodontics]. AB - In the medical literature, and in particular in the field of periodontology, one could observe since several years an increasing interest in diagnostic tests. However, these are often difficult to comprehend. Indeed, understanding the value of these tests implies mastering the meaning of certain basic notions such as sensitivity, specificity and predictive value. The aim of this paper is to present these essential theoretical notions in a simple way and to illustrate them using clinical examples. Finally, several applications of these tests in the field of periodontology will be discussed. PMID- 1455202 TI - [The late results with a fixed denture in less well-off adults. A retrospective study]. AB - In this retrospective study 141 patients were re-examined after having been treated with at least two crowns or one fixed bridge each at the Cantonal Public Dental Clinic of Zurich (Volkszahnklinik) between 1974 and 1984. After an average "wearing time" of more than 9 years, 88% of the crowns and 92% of the bridges were still in function. 4 patients had already lost all their reconstructions incorporated in the "Volkszahnklinik" and were not examined clinically. 115 (84%) of the remaining 137 patients were satisfied with their reconstructions. The mean papillary bleeding index (PBI) was significantly higher on crowned teeth compared to the untreated teeth. The mean probing depth of the crowned premolars and incisors was also significantly higher compared to that of the natural teeth. The results of the study show that the success rate of fixed reconstructions fitted at the Cantonal Public Dental Clinic of Zurich are within the ranges reported by other similar institutions. PMID- 1455203 TI - Treatment of Class II, div. 1 malocclusion with the activator and with the Begg technique. AB - The effect of treatment of Angle Class II, division 1 malocclusion with an Andresen activator or with the Begg technique with or without premolar extraction was studied retrospectively with X-ray cephalometry. The treatment with the Begg technique was followed by a phase of retention with an activator. Three groups of 25 children who had been treated with one of the methods were compared regarding facial morphology and soft tissue profile before and after the treatment and changes during the period of treatment. The treatment effect (correction of the distal occlusion and normalisation of the overjet and overbite) was similar with the three methods. The overjet was mainly corrected through skeletal changes, which accounted for 70%, 77% and 62% of the overjet correction produced by the activator, Begg extraction and Begg non-extraction treatment, respectively. Thus, all three methods of treatment had a skeletal (orthopedic) effect. The dental component of the overjet correction was with all three methods of treatment a retroclination of the upper incisors. This was to some extent offset by a retrusion of the lower incisors, which also occurred in all groups. The facial morphology and the soft tissue profile after the treatment were similar in the three groups. There were no differences in the soft tissue profile and only marginal differences in facial morphology as a result of the three methods of treatment. PMID- 1455205 TI - [Gingival recession. Esthetic viewpoints in the therapy of gingival recession]. PMID- 1455204 TI - [The microstructure of leucite-reinforced glass ceramics]. AB - The dentine materials of the metal ceramic systems VMK 68 and Biodent as well as the ceramics of all ceramic systems Duceram, Cosmotech, Optec, IPS-Empress and Corum were tested for their leucite content. The structure analysed in the scanning electron microscope showed leucite in the dendritic and idiomorphic form. X-ray diffraction analyses verified the leucite content in metal ceramic systems and ceramics of the nonbonded systems. Comparing the metal ceramic systems with the nonbonded systems, an increase in leucite content was observed in the nonbonded systems. PMID- 1455206 TI - [Preprosthetic surgery and implantology. The effect of oral implantology on preprosthetic surgery in edentulous patients]. PMID- 1455207 TI - [Foreign dentists will not have to have passed a Swiss state exam. Interview by Kurt Venner]. PMID- 1455208 TI - [AIDS prevention measures are valid despite the HIV criticism]. PMID- 1455209 TI - [Fluoride mouth-rinse tablets registered]. PMID- 1455210 TI - [Expanded epidemiological data census in HIV]. PMID- 1455211 TI - [The dental hygienist and the prophylaxis assistant: the purposes and future of these two professions. Interview by Catherine Strahm and Kurt Venner]. PMID- 1455212 TI - [Causes of prenatal foal loss in Switzerland]. AB - In Switzerland during the foaling season 1988 and 1989 the cause of abortion in 60 foals was investigated. Special attention was paid to infections with equine herpesvirus 1 (EHV 1). Diagnosis were based on post-mortem, histopathological, bacteriological and immunofluorescence investigation. The results confirm data from other countries, that EHV 1 is the most prevalent viral (20%) cause of abortion, followed by various bacterial agents (12%). Other causes were umbilical torsion, twin pregnancy and malformations. In 18% of the cases the investigation of fetuses did not give any results as to the cause of abortion, suggesting maternal factors as only cause of abortion. PMID- 1455213 TI - [Kinetic study of the lumbar vertebrae and the lumbosacral passage in German shepherd dogs. 1. Functional anatomy and kinetic foundation]. AB - In the dog congenital or acquired stenosis of the lumbosacral region is commonly encountered. In humans the lumbosacral junction is the most often affected part of the vertebral column. Lumbosacral instability, one possible etiology for stenosis of the vertebral canal plays an important role in man. This study summarizes the functional anatomy and some important geometric and kinematic considerations necessary for the understanding of the motion (flexion-extension) between two adjacent vertebra. PMID- 1455214 TI - [Serious reactions after the TSH-stimulation test in the dog]. AB - The thyrotropin response test is the most common test for the diagnosis of hypothyroidism. Here we report serious adverse effects in two dogs after intravenous administration of bovine TSH. The clinical signs were consistent with an anaphylactoid or anaphylactic reaction. In both cases a previous sensibilization with bovine TSH can be excluded. We discuss the etiology and emphasize the most probable cause to be an anaphylactoid reaction. Preventive measures are discussed. PMID- 1455215 TI - [Oscillating potentials on the B-wave of the ERG in the dog]. AB - The oscillatory potentials (OP) on the b-wave of the canine ERG are characterized. Normal values for an OP-index, implicit times and periodicity are given. The OP-index increases during dark adaptation as well as with increasing stimulus intensities for white light flashes. Scotopic blue and red stimuli, although balanced for the maximum b-wave amplitude, surprisingly result in higher OP-indices for red flashes. Implicit times decrease for all OP with increasing stimulus intensities. Scotopic balanced red light results in OP with markedly reduced implicit times compared to blue light stimulation. The intervals between two OPs remain constant during dark adaptation, however, intervals between OPs with longer implicit times tend to be shorter. In contrast, the b-waves for scotopic balanced stimuli show rhythmic oscillations with constant intervals between them, the intervals being shorter for blue light than for red light. The intervals between OPs tend to become shorter with increasing stimulus intensities. This investigation indicates that OPs are influenced but not generated by photoreceptors. The examination of a dog with optic nerve hypoplasia indicates that the ganglion cells do not contribute to the biogenesis of OPs. The prognostic value of OPs in the early diagnosis for hereditary retinal degenerations in the dog is discussed. PMID- 1455216 TI - Left-handed comments. PMID- 1455217 TI - Left-handed comments. PMID- 1455218 TI - Left-handed comments. PMID- 1455219 TI - Amber trees. PMID- 1455220 TI - AIDS clinical trial to go ahead. PMID- 1455221 TI - Violence Research. NRC panel provides a blueprint. PMID- 1455222 TI - Genome Diversity Project. Anthropologists climb (gingerly) on board. PMID- 1455223 TI - A few of the chosen. PMID- 1455224 TI - French public goes for blood. PMID- 1455225 TI - From 'hunter magic,' a pharmacopeia? PMID- 1455226 TI - Antibodies without immunization. PMID- 1455227 TI - Evidence from 12S ribosomal RNA sequences that onychophorans are modified arthropods. AB - The evolutionary relationships of the onychophorans (velvet worms) and the monophyly of the arthropods have generated considerable debate. Cladistic analyses of 12S ribosomal RNA sequences indicate that arthropods are monophyletic and include the onychophorans. Maximum parsimony analyses and monophyly testing within arthropods indicate that myriapods (millipedes and centipedes) form a sister group to all other assemblages, whereas crustaceans (shrimps and lobsters) plus hexapods (insects and allied groups) form a well-supported monophyletic group. Parsimony analysis further suggests that onychophorans form a sister group to chelicerates (spiders and scorpions) and crustaceans plus hexapods, but this relationship is not well supported by monophyly testing. These relationships conflict with current hypotheses of evolutionary pathways within arthropods. PMID- 1455228 TI - Activation of a plant gene by T-DNA tagging: auxin-independent growth in vitro. AB - A transferred DNA (T-DNA) tagging vector with the potential to produce dominant mutations was used with cocultured Agrobacterium tumefaciens and protoplasts to tag genes involved in the action of the plant growth substance auxin. Transgenic calli were selected for their ability to grow in the absence of auxin in the culture media. From one experiment, 12 calli that displayed this phenotype were recovered, of which 11 were able to regenerate into plants. In one plant studied in detail, protoplast division in the absence of auxin genetically cosegregated with a single T-DNA insert. A messenger RNA encoded by a 6.4-kilobase sequence of plant genomic DNA rescued from the mutant is overexpressed relative to untransformed plants. The genomic DNA, as well as a cognate complementary DNA, once transfected into protoplasts promote growth and cell division in vitro in the absence of exogenously added auxin. PMID- 1455229 TI - Map-based cloning of a gene controlling omega-3 fatty acid desaturation in Arabidopsis. AB - A gene from the flowering plant Arabidopsis thaliana that encodes an omega-3 desaturase was cloned on the basis of the genetic map position of a mutation affecting membrane and storage lipid fatty acid composition. Yeast artificial chromosomes covering the genetic locus were identified and used to probe a seed complementary DNA library. A complementary DNA clone for the desaturase was identified and introduced into roots of both wild-type and mutant plants by Ti plasmid-mediated transformation. Transgenic tissues of both mutant and wild-type plants had significantly increased amounts of the fatty acid produced by this desaturase. PMID- 1455230 TI - Dynamics of ribozyme binding of substrate revealed by fluorescence-detected stopped-flow methods. AB - Fluorescence-detected stopped-flow and equilibrium methods have been used to study the mechanism for binding of pyrene (pyr)-labeled RNA oligomer substrates to the ribozyme (catalytic RNA) from Tetrahymena thermophila. The fluorescence of these substrates increases up to 25-fold on binding to the ribozyme. Stopped-flow experiments provide evidence that pyr experiences at least three different microenvironments during the binding process. A minimal mechanism is presented in which substrate initially base pairs to ribozyme and subsequently forms tertiary contacts in an RNA folding step. All four microscopic rate constants are measured for ribozyme binding of pyrCCUCU. PMID- 1455231 TI - Three-dimensional structure of dimeric human recombinant macrophage colony stimulating factor. AB - Macrophage colony-stimulating factor (M-CSF) triggers the development of cells of the monocyte-macrophage lineage and has a variety of stimulatory effects on mature cells of this class. The biologically active form of M-CSF is a disulfide linked dimer that activates an intrinsic tyrosine kinase activity on the M-CSF receptor by inducing dimerization of the receptor molecules. The structure of a recombinant human M-CSF dimer, determined at 2.5 angstroms by x-ray crystallography, contains two bundles of four alpha helices laid end-to-end, with an interchain disulfide bond. Individual monomers of M-CSF show a close structural similarity to the cytokines granulocyte-macrophage colony-stimulating factor and human growth hormone. Both of these cytokines are monomeric in their active form, and their specific receptors lack intrinsic tyrosine kinase activity. The similarity of these structures suggests that the receptor binding determinants for all three cytokines may be similar. PMID- 1455232 TI - Consequences of replication fork movement through transcription units in vivo. AB - To examine the basis for the evolutionary selection for codirectionality of replication and transcription in Escherichia coli, electron microscopy was used to visualize replication from an inducible ColE1 replication origin inserted into the Escherichia coli chromosome upstream (5') or downstream (3') of rrnB, a ribosomal RNA operon. Active rrnB operons were replicated either in the same direction in which they were transcribed or in the opposite direction. In either direction, RNA polymerases were dislodged during replication. When replication and transcription were codirectional, the rate of replication fork movement was similar to that observed in nontranscribed regions. When replication and transcription occurred in opposite directions, replication fork movement was reduced. PMID- 1455233 TI - Encoding of a homolog of the IFN-gamma receptor by myxoma virus. AB - Many poxvirus-encoded virulence factors have been identified as proteins that are secreted from infected cells. The major secreted protein (37 kilodaltons) from cells infected with myxoma virus is encoded by the M-T7 open reading frame. This protein has significant sequence similarity to the human and mouse receptors for interferon-gamma (IFN-gamma). Furthermore, the myxoma M-T7 protein specifically binds rabbit IFN-gamma and inhibits the biological activity of extracellular IFN gamma, one of the key regulatory cytokines in the host immune response against viral infections. PMID- 1455234 TI - Regulation of the differentiation of teratocarcinoma cells into primitive endoderm by G alpha i2. AB - The amount of the heterotrimeric G protein subunit G alpha i2 decreases after the induction of F9 teratocarcinoma cells to become primitive endoderm in the presence of retinoic acid (RA). The reduction of the G alpha i2 protein in F9 cells by antisense RNA expression was associated with (i) loss of receptor mediated inhibition of adenylyl cyclase; (ii) decreased cell doubling time; (iii) induction of a primitive, endoderm-like phenotype in the absence of RA; and (iv) production of the differentiation marker tissue-type plasminogen activator. Expression of a constitutively active, mutant G alpha i2 blocked RA-induced differentiation. These data suggest the involvement of G alpha i2 in the control of stem cell differentiation and provide insight into the involvement of G proteins in growth regulation. PMID- 1455235 TI - Nitric oxide and arginine-evoked insulin secretion. PMID- 1455236 TI - Polyamine depletion and drug-induced chromosomal damage: new results. PMID- 1455237 TI - NIH expenditures: extramural versus intramural. PMID- 1455238 TI - Regulations for genetically engineered foods. PMID- 1455239 TI - IL-1 beta and Escherichia coli. PMID- 1455240 TI - AIDS story prompts libel suit. PMID- 1455241 TI - Pediatric AIDS vaccine trials set. PMID- 1455242 TI - French officials panic over rare brain disease outbreak. PMID- 1455243 TI - Roche gets tough on illicit sales of PCR reagent. PMID- 1455244 TI - NIH takes new tack on gene mapping. PMID- 1455245 TI - Production and initial characterization of bionites: materials formed on a bacterial backbone. AB - The addition of soluble metal salts of calcium, iron, or copper to cultures of Bacillus subtilis grown in web form nucleated precipitation at the surface of the bacterial cell walls. The mineralized cell filaments can be drawn into a fiber that when dried consists of a bacterial thread backbone carrying an inorganic solid. The ratios of organic to inorganic components (by weight) in the stiff brittle materials, called bionites, were: 1.08 for fe(2)bactonite, 1.8 for calbactonite, 2.3 for fe(3)bactonite, and 5 for cu(2)bactonite. X-ray photoelectron spectra suggest that the fe(3)bactonite contains Fe2O3, that calbactonite contains calcium carbonate, and that cu(2)bactonite contains CuCl (Cu I). Acid-base reactions of the bionites are compatible with these identifications. Burning out the organic phase of the febactonites yields a black magnetic material, presumably magnetite. The burnt cubactonite appears to yield elemental Cu(s). Calbactonite upon hydration was able to retain a genetically engineered enzymatic activity. PMID- 1455246 TI - Behavioral lifetime of human auditory sensory memory predicted by physiological measures. AB - Noninvasive magnetoencephalography makes it possible to identify the cortical area in the human brain whose activity reflects the decay of passive sensory storage of information about auditory stimuli (echoic memory). The lifetime for decay of the neuronal activation trace in primary auditory cortex was found to predict the psychophysically determined duration of memory for the loudness of a tone. Although memory for the loudness of a specific tone is lost, the remembered loudness decays toward the global mean of all of the loudnesses to which a subject is exposed in a series of trials. PMID- 1455247 TI - Modulation of vascular endothelial permeability by thrombin. PMID- 1455248 TI - Vascular effects of thrombin. PMID- 1455249 TI - Components and assembly of the factor X activating complex. PMID- 1455250 TI - Ligand binding to GPIIb-IIIa: a status report. PMID- 1455251 TI - A role for alpha-thrombin in polymorphonuclear leukocyte recruitment during inflammation. PMID- 1455252 TI - Molecular interactions between heparin cofactor II and thrombin. PMID- 1455253 TI - [Role of the hypophysis in the renal responses upon stimulation of the brain osmoreceptor]. AB - The experiments were performed in rats anaesthetized with alpha-chloralose and urethane. Intracerebroventricular administration of hypertonic saline (icv. HS) resulted in an increase in renal plasma flow rate, glomerular filtration rate, urine flow rate, urinary sodium excretion, urinary potassium excretion, and osmolar clearance, and a decrease in free water clearance. These responses were abolished in hypophysectomized rats, but were not significantly affected by intravenous injection of vasopressin (VP) receptor (V1 and V2) antagonist. The urinary dopamine (DA) excretion did not change significantly after icv. HS. Moreover, administration of benserazide, an inhibitor of the enzyme L-aromatic amino acid decarboxylase that converts L-dopa to DA, did not attenuate the diuresis and natriuresis induced by icv. HS. These results suggest that the renal responses upon stimulation of the brain osmoreceptor are dependent on the integrity of the hypophysis, while the VP and DA are not essential to these renal responses. The hypophysial factors responsible for the icv. HS-induced renal responses remain to be explored. PMID- 1455254 TI - [The effects of stimulation of the brain osmoreceptor on the tubular reabsorption of sodium, chloride and potassium in rats]. AB - The tubular reabsorption of sodium, chloride and potassium was studied with micropuncture technique and electron probe X-ray microanalysis before and following intracerebroventricular administration of hypertonic saline (icv. HS) in rats. At the late proximal convoluted tubules, the fractional delivery of sodium increased from 53.0 +/- 2.1% to 66.0 +/- 2.9% (P < 0.01), the fractional delivery of chloride increased from 65.4 +/- 3.4% to 78.2 +/- 3.9% (P < 0.05), but the fractional delivery of potassium and tubular fluid osmolarity were unaltered. At the early distal convoluted tubules, the fractional delivery of sodium increased from 8.2 +/- 0.9% to 13.6 +/- 1.8% (P < 0.05), the fractional delivery of chloride increased from 5.4 +/- 0.8% to 9.5 +/- 1.4% (P < 0.05), the tubular fluid osmolality increased from 139.8 +/- 6.9 mOsm/kg H2O to 181.3 +/- 15.6 mOsm/kg H2O2 whereas fractional delivery of potassium did not show significant change. Under the condition of diuresis provoked by the intravenous administration of furosemide the kaliuresis induced by icv. HS was abolished, while the icv. HS-elicited diuresis and natriuresis remained unaffected. These results indicate that stimulation of the brain osmoreceptor inhibits the proximal tubular reabsorption of sodium chloride which in turn enhances sodium-potassium exchange in the distal tubules and collecting ducts. PMID- 1455255 TI - [Effects of calcium blockers on the performance of left and right ventricles during acute hypoxia]. AB - In anesthetized and thoracotomized 20 adult dogs under artificial respiration, the effects of calcium blockers (nifedipine, diltiazem and verapamil) on the mechanics of the left and right cardiac pumps under acute hypoxia were observed. The left and right ventricular pressure (LVP and RVP) and their dp/dt (+/- dp/dtmax), aortic flow (Fa), pulmonary pressure (Ppa) and heart rate (HR) were recorded. After treatment with calcium blockers, LVP and L +/- dp/dtmax decreased, and Fa increased, while RVP, R +/- dp/dtmax and Ppa all tended to increase. These results showed that the effects of calcium blockers on the performance of the left and right ventricles were different, suggesting that the dependence of left and right myocardium on calcium was different in degree. The mechanics of the left and right ventricles responded differently to calcium blockers under acute hypoxia. After treatment with calcium blockers, pressor responses on LVP by acute hypoxia disappeared. There was a great increase in Fa. Decrease in pressor response of RVP and Ppa was also observed in acute hypoxic dogs receiving verapamil and diltiazem. Comparing the effects of nifedipine, diltiazem and verapamil on the mechanics of the left and right cardiac pumps under acute hypoxia, it appears that diltiazem exerts beneficial effect on the performance of cardiac pump under acute hypoxia. PMID- 1455256 TI - [Microinjection of 5-HT into the rostral ventrolateral medulla reduced the hyperviscosity and elevation of blood pressure induced by stress]. AB - Experiments were carried out on 62 wistar rats. The hyperviscosity and elevation of blood pressure were induced by hanging and restraining the rats with their four limbs tied on a frame. It was found that microinjection of 5-HT (25 micrograms/10 microliters) into the 4th ventricle of the brain or bilateral microinjection of 5-HT (4 micrograms/0.5 microliters/site) into rostral ventrolateral medulla (rVLM) reduced stress-induced hyperviscosity (p < 0.01) and elevation of blood pressure (p < 0.01). The effect of 5-HT injected into the 4th ventricle or rVLM was blocked by bilateral microinjection of cinanserine (4 micrograms/0.5 microliter/site) into rVLM. These results suggest that microinjection of 5-HT into 4th ventricle and rVLM could reduce stress-induced hyperviscosity and elevation of blood pressure and these effects were probably mediated via 5-HT receptors in the rVLM. PMID- 1455257 TI - [Role of endothelium-derived relaxing factor in the contractions of intrapulmonary artery induced by oxygen-derived free radicals in chronic hypoxic rat]. AB - The role of endothelium-derived relaxing factor (EDRF) on the effect of oxygen derived free radicals (generated by xanthine-xanthine oxidase system) on intrapulmonary arterial in chronic hypoxic rats was studied by a microbioassay method. Intrapulmonary artery rings with intact or denuded endothelium of hypoxic (5,000 m, 10 days) and normoxic rats were prepared for observation of oxygen derived free radicals induced contraction. It was shown that oxygen-derived free radicals induced contractions of intrapulmonary arterial rings with intact endothelium were obviously augmented in hypoxic rats than in normoxic controls. The augmented responses could be further potentiated by the addition of EDRF inactivator reduced hemoglobin (RHb), but diminished or even abolished by applying superoxide dismutase (Cu-Zn SOD). However, no effect on denuded rings was observed when RHb or SOD was added. It is concluded that chronic hypoxia may attenuate the action of EDRF in the enhancement of the reactivity of intrapulmonary artery to oxygen-derived free radicals. PMID- 1455258 TI - [Effect of intraventricular administration of histamine and its receptor agonists on pentagastrin-induced gastric acid secretion in rats]. AB - The present study shows the dual effects of intraventricularly injected histamine (0.25-2.0 micrograms/5 microliters) on pentagastrin-induced gastric acid secretion. Male Wistar rats weighing 200-300 g were anesthetized with intraperitoneal sodium pentobarbital. Gastric acid was continuously washed out with 37 degrees C saline solution by means of a perfusion pump. On the background of continuous intravenous infusion of pentagastrin [7.5 micrograms/(kg.h),] histamine (0.25 microgram/5 microliters) or 2-pyridylethylamine (PEA, 10 micrograms/5 microliters), a H1-receptor agonist, was injected into the third ventricle through a chronically implanted canula. The acid output decreased 10 min after injection and did not recover at 90 min. When the dose of histamine was increased to 1.0 micrograms or 2.0 micrograms, dual effects appeared. The acid output decreased respectively in 73% or 50% of the animals, while in the rest 27% and 50% of the animals, the acid output increased. H2-receptor agonist dimaprit (10 micrograms/5 microliters, i.c.v.) or impromidine (0.1 micrograms/5 microliters, i.c.v.) had no pronounced effect on pentagastrin-induced acid secretion. Pretreatment with diphenhydramine (16 micrograms/0.2 ml or 32 micrograms/0.2 ml, i.m.) abolished the inhibitory effect of histamine and PEA on acid secretion. These results suggest that histamine may be involved in the central regulation of gastric acid secretion, and the inhibitory effect may be mediated by H1-receptors in the brain. The mechanism underlying the production of the dual effects of histamine is unknown. PMID- 1455259 TI - [Effects of castration and testosterone-replacement on hypothalamic and plasma luteinizing hormone-releasing hormone levels in the aged male rat]. AB - Hypothalamic and plasma luteinizing hormone-releasing hormone (LHRH) levels following orchidectomy (ORDX) and testosterone (T)-replacement were compared between young (2-3 months old) and aged (24-26 months old) male rats by radioimmunoassay. Plasma T level and hypothalamic LHRH content are markedly decreased in the aged rat as compared to those of the young rat, whereas plasma LHRH levels are similar in the two groups. Following ORDX and ORDX plus T replacement, plasma T levels in both groups are about the same, whereas the rates of variation of hypothalamic and plasma LHRH levels in the aged rat are significantly lower than those in the young rat. These results suggest that the negative feedback mechanism of the hypothalamic LHRHergic system is impaired in the aged rat, which may be one of the important reasons causing age-dependent deterioration of the functional control of hypothalamic-pituitary-testicular axis. PMID- 1455260 TI - [Hormonal regulation of PAI-1 secretion by cultured rat ovarian cells]. AB - Rat ovarian cells produce not only plasminogen activator (tPA) but also plasminogen activator inhibitor type 1 (PAI-1), and their coordinated geneexpression induced by gonadotropins are thought to be responsible for follicular rupture. In this study, it was demonstrated that (1) theca interstitial compartment synthesizes the majority of PAI-1 activity in the ovary before ovulation, the follicular wall may therefore serve as a specific barrier to prevent the secretion of PA into the extrafollicular compartment; (2) Granulosa cells contribute only small amount of ovarian PAI-1 activity, but synthesize most of tissue-type plasminogen activator activity involved in the process leading to ovulation: (3) Since only matured cumulus-oocyte complexes secrete high level of tPA and PAI-1, both tPA and PAI-1 activity in the conditioned medium may be used as reliable markers for evaluating oocyte quality for in vitro fertilization. PMID- 1455261 TI - [Role of endothelin in the pathogenesis of rat experimental hypertension produced by aorta narrowing and saline uptake]. AB - Endothelin is a bioactive polypeptide released from vascular endothelium, which has a strong action promoting vascular contraction, proliferation and hypertrophy of vascular smooth muscle cells. The present investigation was performed on the hypertensive rat produced by narrowing abdominal aorta and drinking saline. It was observed that the level of plasma endothelin in the hypertensive rats was doubled (9.70 +/- 0.68 vs. sham group 4.11 +/- 0.33 pg/ml, P < 0.01), and administration of specific endothelin-antiserum into hypertensive rats significantly attenuated the increase in the blood pressure (18.97 + 1.32 vs. 27.33 + 0.09 kPa in untreated hypertensive rats, P < 0.01), and dramatically ameliorated malfunction resulting from myocardial hypertrophy. The results suggest that endothelin is an important factor in the pathogenesis of hypertension, and that inhibition of endothelin action may be a new effective way in prevention and therapy of hypertension. PMID- 1455262 TI - [Alterations of pulmonary arterial pressure following intraventricular injection of histamine in rabbits]. AB - The changes of the pulmonary arterial pressure (PAP) following microinjection of histamine (HA) into the lateral ventricle in the rabbit were investigated. It was found that (1) Intraventricular injection of HA (50 micrograms) induced either an increase (in the majority) or a decrease in PAP and cardiac output (CO), or a biphasic response characterized by a decrease followed by an increase. Slowing down of heart rate (HR) and elevation of carotid arterial pressure (CAP) were observed accordingly. (2) After bilateral cervical vagotomy or fixing the heart rate by cardiac pacing, drop in CO and PAP in response to HA was no longer observed. Instead, they even showed some constant increase. The pressor response of PAP and CAP to HA could be partially blocked by phentolamine applied intravenously without affecting the increment of CO. On the other hand, intravenous injection of propranolol could totally block the HA-induced increment of CO, but not affect the pressor responses of PAP and CAP. Intravenous injection of hexamethonium or combined application of phentolamine and propranolol could completely abolish all the increment responses in CO, PAP and CAP to HA. (3) The cardiovascular responses to HA could be blocked by the H1 receptor blocker chlorpheniramine, but not by H2 receptor blocker-cimetidine. It is thus assumed that HA applied intraventricularly can activate the central H1 receptor, thus inducing an increase in the cardiac output and vasoconstriction of pulmonary and peripheral vessels giving rise to an elevation of both PAP and CAP by way of sympathetic nerve. Central application of HA also induces bradycardia by activating vagus nerve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455263 TI - [The respiratory facilitating effects by electrical and chemical stimulation of central nucleus amygdala]. AB - Experiments were performed on fifty urethan anesthetized (1 g/kg) rabbits of both sexes, vagotomized and spontaneously breathing. The respiratory responses to electrical and chemical stimulation of ACE were observed. The results were as follows: 1. Long train electrical stimulation of ACE caused significant respiratory facilitating effects: inspiratory prolongation and increase of respiratory rate and depth. 2. Short brust of electrical stimulation administered in ACE during the mid inspiratory and expiratory phases elicited the prolongation of inspiratory phase and the expiratory off-switch (EO-S) effect, respectively. 3. Microinjection of monosodium L-glutamate (MSG) (1 mol/L, 1 microliter) into ACE produced the similar respiratory effects as that of electrical stimulation. 4. Control experiments had no significant effect on respiration. The results showed that the activation of neurons in ACE caused facilitation of respiration. It is suggested that ACE region may take an important part in facilitating the basic respiratory rhythm. PMID- 1455264 TI - Triglycerides and coronary artery disease. PMID- 1455265 TI - Malaria: smears or buffy coats? PMID- 1455266 TI - Comparison of the quantitative buffy coat technique with the conventional thick blood film technique for malaria case detection in the field. AB - The quantitative buffy coat (QBC) technique was compared with the conventional thick blood film technique in a malaria survey carried out in a mesoendemic area of malaria in Betau, Pahang, Malaysia. The QBC technique was found to be a rapid technique but had a sensitivity of about 56% and a specificity of 95%, using the thick blood film method as the "gold standard". Malaria species identification was unsatisfactory with the QBC technique as it could identify parasites correctly in only about 60% of specimens. It was unable to detect as positive about 58% of specimens which had parasite counts < or = 500 per ul but could detect about 94% of those with counts > 500 per ul. This difference in positive detection rate was significantly different (p < 0.05). It cannot quantify parasitemia easily and the specimens cannot be stored for future reference and for quality control purposes. It is therefore concluded that the QBC technique cannot replace the classical thick blood film technique for use in malaria control programmes. Its use may be appropriate in situations like busy blood banks and outpatient clinics where rapid screening of malaria infection is needed but where experienced malaria microscopists may not be available. PMID- 1455267 TI - A review of patients with a 'normal' coronary angiogram over a 3-year period. AB - Over a period of 36 months, we detected 54 patients with normal coronary arteries or non-critical coronary artery stenosis within our study series of coronary angiography. We studied these patients to determine their clinical, electrocardiographic, stress testing and angiocardiographic characteristics. We detected among them a preponderance of female sex and a higher incidence of ethnic Indians. The majority of the patients studied had one or more coronary risk factors. 52% had a normal resting ECG. In those with a positive stress test and reports available for review, there is a near equal distribution of horizontal and J-type ST depression. Those patients with a positive treadmill tend to have a higher left ventricular end diastolic pressure (LVEDP) at cardiac catheterization. We also noted in this group of patients a higher proportion with a small distal left anterior descending artery. These patients also tend to have higher LVEDP even in the presence of normal left ventriculogram. Our current series suggests the possibility of raised left ventricular end-diastolic pressure and the presence of a "small distal left anterior descending artery" syndrome in association with patients with a 'false positive' treadmill test. PMID- 1455268 TI - The profile of ICU admissions for acute severe asthma in a general hospital. AB - The clinical profile of 22 patients admitted to the Intensive Care Unit of Alexandra Hospital over a 2-year period was studied. The mean age was 48.8 years with a majority in the older age group. The attacks leading to admission were generally rapid in evolution with 59% having symptoms for less than 12 hours and 84% for less than 24 hours. Most had a history of severe asthma, and of long duration. The pre-admission therapy had been suboptimal in the majority. Severe respiratory acidosis was a predominant feature. 68% were transferred to the ICU within one hour of arrival at hospital. Mechanical ventilation was required in 86.4% of cases, but the duration of ventilation was usually short. There was no serious complication due to barotrauma. Overall mortality was 23% (5/22). Problems in patient education remain a major hurdle in our attempt to reduce asthma mortality. PMID- 1455269 TI - Nontuberculous mycobacterial disease of the lungs in Singapore. AB - Information on lung disease due to nontuberculous mycobacteria (NTM) is lacking in Singapore. A review of the records at the Central Tuberculosis Laboratory up to the end of 1988 showed that 23 patients seen between 1976 to 1988 inclusive had cultures which were repeatedly positive for NTM. Of the 23 cases analyzed, 15 were found to have lung disease which could be attributed to NTM. There were 9 males and 6 females with a male to female ratio of 1.5:1. The patients were either middle aged or elderly. The 2 main infective agents were M avium intracellulare and M kansasii. Ten (67%) patients had moderately advanced and 5 (33%) had far advanced disease. Concurrent disease of the lung was present in 10 patients (67%). Seven (47%) patients had bronchiectasis, 1 (7%) had both bronchiectasis and chronic obstructive pulmonary disease (COPD) and 2 (13%) had COPD. A past history of pulmonary tuberculosis was present in 10 patients (67%). Lung disease due to NTM is uncommon in Singapore. Treatment failure was attributed to poor compliance, a possibility which could not be excluded in those patients who had adverse reactions. PMID- 1455270 TI - Some observations on the epidemiology of peptic ulcer disease in Singapore. AB - Several lines of evidence suggest that, of the three main races of Singapore, peptic ulcers are more common among the Chinese and Indians when compared to the Malays. These include studies on hospital series of patients with or without appropriate control groups, studies on the incidence of surgery for perforated ulcer as well as mortality statistics. A reduction in the Chinese:Malay difference in the incidence of perforated ulcer over three decades suggests that environmental factors are involved in producing these racial differences. However, we have to date been unable to determine the factor(s) responsible. The incidence of perforated ulcer in Singapore is increasing while ulcer mortality is declining. This is similar to the situation in Hong Kong but different from that in the western countries. PMID- 1455271 TI - Blood pressure tracking as an indicator of hypertension risk. AB - The significance of high blood pressure to cardio- and cerebrovascular disease is well recognized. The associated mortality and morbidity risks call for multiple approaches to control the development of high blood pressure. Recent studies have shown that precursors of cardiovascular disorders may be apparent from a young age, and that these can persist and contribute to disease in later life. With regard to blood pressure, the phenomenon of persisting at the same rank has been referred to as tracking. This allows for the possible identification of high-risk groups, for whom early intervention can be initiated. In this paper, some of the findings of studies on blood pressure tracking are reviewed. PMID- 1455272 TI - Intravenous sedation for upper gastrointestinal endoscopy: Midazolam versus propofol. AB - Propofol was compared with Midazolam for sedation during upper gastrointestinal endoscopy in a randomised, double blind study. Both drugs were equally acceptable to endoscopists and patients. There was significant oxygen desaturation after sedation and during endoscopy (p < 10(-6)). Significantly more patients in the propofol group could remember the diagnosis which was revealed to them immediately after the gastroscopy (p < 0.001). PMID- 1455273 TI - Effects of radiation on hearing in patients with malignancies of head and neck. AB - Patients with normal hearing at the start of radiation were tested for hearing during (30 GY) and at the end of radiation therapy (45-60 GY) in order to determine if there was any alteration in their pure tone hearing thresholds. A significant increase in the hearing threshold was found at high frequencies at the end of therapy. At the end of the course of radiation, clinical findings suggestive of middle ear changes due to radiation were seen in 33% of the ears. Patients whose ears are included in the field of radiation may have to be forewarned to expect a loss in their acuity of hearing, especially those whose professional life may depend on it. PMID- 1455274 TI - AIDS and us: are we failing to prevent a highly preventable disease? PMID- 1455275 TI - Myopia produced in young chicks by intermittent minimal form visual deprivation- can spectacles cause myopia? AB - Spectacle use has been postulated to aggravate or cause human myopia. Form visual deprivation, by complete full-time occlusion or refractive lenses, has been demonstrated to cause axial myopia in animals. We raised young chicks in conditions which closely approximate plano spectacle wear in humans. In addition, we sought to achieve more physiological conditions of form deprivation. Nine newborn chicks were raised with intermittent monocular visual deprivation and their eye growth and refraction monitored by retinoscopy, ultrasonic A-scan biometry and with a travelling microscope. After hatching, the nictitating membranes were sutured for 3-4 days. This was followed by a transparent plano plastic cover over the same eye for 3-4 days per week. After 3 weeks, the manipulated eyes were more myopic (mean refraction -0.72 D, axial length 13.11 mm) than fellow eyes (+0.83 D, 11.99 mm) (p < 0.05 and p < 0.01 respectively). These results suggest that the chick eye is exquisitely sensitive to disturbances in the visual environment; intermittent minimal manipulation by conditions simulating spectacle wear in man was myopiagenic. It is postulated that spectacles can cause form visual deprivation of foveal and nonfoveal neurons (and hence myopia) by reducing luminance and contrast, chromatic and spherical aberration (in nonfoveal neurons) and restriction and distortion from the frame. PMID- 1455276 TI - The rotary influence of articular contours during passive glenohumeral abduction. AB - Automatic external rotation at the glenohumeral joint is an essential component of active as well as passive elevation of the arm through abduction. Recent studies have demonstrated this automatic rotation to be present during passive abduction using cadaveric glenohumeral joints even in the absence of extra articular influences like the coraco-acromial arch and glenohumeral muscles. In the present study, simulated abduction in disarticulated cadaveric joints was shown to be associated with automatic external rotation suggesting a role in this mechanism for the articular contours. PMID- 1455277 TI - The role of computed tomography in the evaluation of retinoblastoma. AB - To assess the importance of Computed Tomography(CT) in the evaluation of retinoblastoma, we reviewed thirteen cases of retinoblastoma which presented at Hospital University Sains Malaysia, Kelantan, Malaysia, from August 1986 to June 1991. High resolution computed tomography of the orbits was performed in all patients prior to therapy. Nine patients (69%) had unilateral and four (31%) had bilateral retinoblastoma. The interesting features were the remarkably high incidence in the right eye (89%) as compared to the left eye (11%) in unilateral retinoblastoma, and overall predominance of the male population (male to female ratio was 2:1). Computed tomography detected intraocular calcification in 82% of the tumourous eyes. All patients presented at late stages when tumours were of large size. The presence of calcification was not related to the size of the tumour. CT detected calcification in a suspected retinoblastoma with a high degree of accuracy. Computed tomographic evidence of intraocular calcification in children under 3 years of age is highly suggestive of retinoblastoma. PMID- 1455278 TI - The mental diseases hospital, Singapore (1st 100 years)--a short history (Part II). AB - This article (in four parts) traces the history of the first four Mental Hospitals built in Singapore, which were occupied in 1840, 1861, 1887 and 1928. The management of the patients is described; also their lives and deaths. Mention is also made of the doctors and others who looked after them. PMID- 1455279 TI - Non-steroidal anti-inflammatory drugs--uses and complications. AB - Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are important in the management of any inflammatory arthritis. However, all NSAIDs have side effects--NSAID related gastropathy (the most common serious side-effect), reversible NSAID nephropathy, dermal complications, hematologic complications, hepatic complications, central nervous system complications, pulmonary complications etc. Patients who have more severe forms of rheumatic disease, take higher doses of NSAIDs with steroids and suffer concomitant medical illness are at higher risk for these toxicities. In all cases, the benefits from the use of NSAIDs must outweigh the risk. When managing a high risk patient, consider alternate therapy and if an NSAID must be used, always monitor the patient carefully. PMID- 1455280 TI - The antiphospholipid syndrome. AB - The antiphospholipid syndrome (APS) describes an entity characterised by recurrent thrombosis, recurrent spontaneous abortions, thrombocytopenia, and elevated levels of antiphospholipid antibodies (IgG or IgM). The clinical features of APS include manifestations of thrombosis and/or cell damage. There is usually an associated underlying connective tissue disorder. The primary antiphospholipid syndrome refers to the presence of these clinical features without evidence of an associated autoimmune disorder. Detection of these antibodies include the lupus anticoagulant test, VDRL test and assays for anticardiolipin antibodies. Overlapping populations of these antibodies are detected by various immunologic tests. Management is based on the use of immunosuppressives, platelet inhibitors and anticoagulants. PMID- 1455281 TI - Approach to psychiatry--an overview. PMID- 1455282 TI - Wide complex tachycardia. PMID- 1455283 TI - A case report on gangrene following simultaneous traumatic open metatarsophalangeal and interphalangeal dislocations of the left big toe. AB - Simultaneous metatarsophalangeal and interphalangeal dislocations of the big toe are rare injuries. Gangrene of the big toe following open dislocations was reported in a 20-year-old man. PMID- 1455284 TI - Medical treatment of Cushing's syndrome with aminoglutethimide and ketoconazole. AB - We report a 54-year-old Chinese man with Cushing's syndrome from bilateral adrenal adenomata in whom surgery was contraindicated because of his intercurrent medical conditions. Instead, he was successfully treated with aminoglutethimide 0.75 gm/day (which reduced his 24-hour urinary free cortisol from 628 nmol/day to 177 nmol/day in 4 weeks), followed by ketoconazole 0.6 gm/day which continued to suppress the urinary free cortisol level. We conclude that aminoglutethimide or ketoconazole offers a viable non-surgical alternative to the treatment of Cushing's syndrome. PMID- 1455285 TI - Mumps encephalomyelitis. AB - A 7-year-old Indian girl developed complete paralysis of her lower limbs and acute urinary retention 10 days after suffering from mumps. Encephalomyelitis due to mumps was not suspected initially since it is a rare complication of mumps, although relatively well-documented. However, the preceding history of parotitis and the presence of mumps-specific IgM in both blood and cerebrospinal fluid led to the diagnosis. The initially severe acute neurological deficits resolved completely three months after onset of her illness. Serological investigations were helpful in diagnosing neurological complications of mumps in this case, and especially where there is no preceding parotitis. PMID- 1455286 TI - Nasal positive pressure ventilation in the treatment of chronic hypercapnic respiratory failure: a case report. AB - This paper describes the use of a nasal mask to deliver intermittent positive pressure ventilation to treat chronic respiratory failure in one patient with severe kyphoscoliosis. After two months of overnight nasal ventilation at home the patient achieved normal blood gases, showed improved inspiratory muscle strength, effort tolerance and was able to return to work. Intermittent nasal ventilation is a safe and effective ventilatory support modality for some patients with hypercapnic respiratory failure. PMID- 1455287 TI - Overestimation of severity of mitral stenosis during cardiac catheterization due to a large left atrial thrombus. AB - We report a case of mitral stenosis with a large left atrial thrombus which was obstructing pulmonary venous inflow where the conventional use of the pulmonary capillary wedge pressure as an approximation of the left atrial pressure during diagnostic cardiac catheterisation led to the over-estimation of the severity of mitral stenosis. PMID- 1455288 TI - Current diagnosis and treatment of rhinosinusitis--functional endoscopic sinus surgery. PMID- 1455289 TI - Phase I/II study of high-dose rate interstitial radiotherapy for head and neck cancer. AB - From July 1991 through December 1991, a phase I/II study of high-dose rate interstitial radiotherapy for head and neck cancer was performed to determine any acute adverse effects and mucosal reaction as well as the feasibility of this therapy. A total of seven patients with head and neck cancer (tongue: four cases; mouth floor: one case; buccal mucosa: one case; oral mucosa of lower lip: one case) were entered into this study. The dose schedule of high-dose rate interstitial radiotherapy ranged from 35 Gy/ten fractions (bid)/week to 60 Gy/ten fractions/week. No major or minor early complication was observed. Spotted mucositis appeared starting three days after the end of high-dose rate interstitial radiotherapy while confluent mucositis developed and approached a peak at ten days but disappeared by the fourth to eighth week. Early tumor responses of all patients were complete. PMID- 1455290 TI - [Cancer rehabilitation in the Federal Republic of Germany--a critical review from the perspective of rehabilitation psychology]. AB - Against the background of a common criticism of the rehabilitation system, the situation of rehabilitation research and practice in oncology is reviewed. A lack of efforts aimed at vocational rehabilitation as well as the main emphasis in inpatient services is criticized. Till now, outpatient services as well as psychosocial rehabilitation care are not as well established, as they should be with regard to provide assistance in coping with the disease and in adapting to the various disabilities may be followed by cancer. As rehabilitation research in oncology is still at its very beginning, we know little about the acceptance of rehabilitation measures as well as the rehabilitation process in its correlation between outcome criteria. Our own pilot study provides first results concerning vocational rehabilitation and acceptance of medical rehabilitation services. As conclusion, we need more elaborated research in oncological rehabilitation for optimizing and further developing rehabilitation care system especially with respect to outpatient and psychosocial services. PMID- 1455292 TI - [How tolerant are partial dose values? Some additional remarks on the concept of a tolerance dose]. AB - By means of the NSD formula and its modifications (CRE, TDF) evaluated from radiotherapy experience by Ellis, it is possible to estimate the acceptance of applied radiotherapy and fractionation scheme. Because the parameters of the Ellis formula are calculated from patients data, they show a dispersion as usually in biological systems. These dispersions are considered as entrance error. In mathematical transformations errors are multiplied according to the principle of superposition of errors. Especially when judging tolerance values of organs of risk the dispersion is quite important. The problem of dispersion of resulting partial tolerance values is demonstrated by some examples of clinical cases. PMID- 1455291 TI - Water-filtered infrared-A radiation: a novel technique to heat superficial tumors. AB - A novel device consisting of an infrared-A (= ultrared-A) radiation source equipped with a water filter in the radiation path is described which allows for the therapeutic heating of superficial experimental and human tumors. Preliminary studies with agar phantoms showed that heating in the presence of the water cuvette avoids intolerable overheating in the very superficial layers. This effect can be further enhanced by surface cooling with room air such that a stratification of the temperature distribution can be achieved. In subsequent experiments, temperature distributions were recorded in the x-, y- and z-axis of superficial rodent tumors. The results obtained confirm those from the phantom experiments, showing that therapeutically relevant temperatures (T > or = 42 degrees C) could be achieved through the tumor mass to a depth of approximately 1.2 cm. Temperature homogeneity is comparable to that seen in superficial tumors undergoing water-bath hyperthermia. This novel technique has proved to be reliable, is well-tolerated, is easy to apply, and is easily accessible to a larger number of potential users for the local heating of superficial malignancies. PMID- 1455293 TI - Hyperthermia in Clinical Oncology. 6th European BSD Users' Conference. Berlin, October 2-3, 1992. Abstracts. PMID- 1455294 TI - Elevated intraocular pressure, pigment dispersion and dark hypopyon in endogenous endophthalmitis from Listeria monocytogenes. AB - Listeria monocytogenes endophthalmitis occurred in an immunologically competent patient with no identifiable extraocular septic focus. The patient presented with a dark hypopyon and markedly elevated intraocular pressure, and the diagnosis was established by culture and histopathologic examination of ocular fluid. Four of the fourteen reported cases of Listeria monocytogenes endophthalmitis also presented with a dark hypopyon, and all cases had markedly elevated intraocular pressure. The presence of a dark hypopyon and elevated intraocular pressure may indicate endogenous intraocular infection with Listeria monocytogenes, even in an apparently healthy host. PMID- 1455295 TI - Multiple cranial neuropathies: presenting signs of systemic lymphoma. AB - A 58-year-old man four years after orthototic liver transplantation presented with a mental neuropathy, multiple ocular motor nerve palsies, and an upper extremity motor neuropathy. Serial neuroimaging, cerebrospinal fluid analysis, total body computerized tomography and paraesophageal needle biopsy failed to reveal the underlying etiology. Sural nerve biopsy showed endoneurial perivascular infiltration with lymphoid cells, and bone marrow biopsy confirmed the diagnosis of a Burkitt's-type lymphoma. Systemic lymphoma with neural infiltration should be suspected in the immunosuppressed patient who presents with cranial or peripheral neuropathies. PMID- 1455296 TI - Disc swelling: a tall tail? AB - A 30-year-old man presented with monocular visual loss secondary to chronic papilledema, due to an ependymoma involving the spinal cord. No other neurological symptoms were present at the time. Initial neuroradiologic tests as well as laboratory investigations were negative, except for elevated pressure and protein concentration of his cerebrospinal fluid. In spite of intensive investigation, the diagnosis of a spinal cord tumor was delayed for approximately 12 months until he presented with neurologic symptoms attributable to a spinal cord lesion. This is only the fourth case reported of a spinal cord tumor associated with papilledema presenting with visual loss, without any other manifestations of either elevated intracranial pressure, or spinal disease. Possible mechanisms for elevated intracranial pressure in cases of spinal cord tumors are reviewed. PMID- 1455297 TI - Remembrance of Hans Goldmann, 1899-1991. AB - Professor Hans Goldmann died in Bern on November 19th, 1991 at the age of 92 years. His outstanding intellectual capacity was discovered at an early age and demonstrated throughout his life. He was appointed as teaching assistant of the famous A. Cermak von Seysenegg, Chairman of the Institute of Physiology of the German Charles University in Prague. During his stay at the University of Prague, he was influenced by the famous people of his time, such as Einstein (physicist), Mach (physicist and psychophysicist), Lorenz (behavioral scientist), Popper (philosopher), Schlick (physicist and philosopher), Hering (physiologist), and others. Goldmann absorbed the essence of these disciplines to a very large extent. This, together with his remarkable intellect, enabled him to produce outstanding research work within a large spectrum of sciences more or less directly related to ophthalmology. Goldmann became known in particular for his exceptional and fundamental work on perimetry and glaucoma and he managed to cast his basic insight into practical, easy-to-operate, high-precision diagnostic instruments which, several decades after their invention, are still used by every ophthalmologist. He will enter history as one of the very great pioneers in ophthalmology. PMID- 1455298 TI - Complications of NSAID therapy in patients with macular disease. PMID- 1455299 TI - Readers comment on "Herpes zoster ophthalmicus". PMID- 1455300 TI - Readers comment on "Herpes zoster ophthalmicus". PMID- 1455301 TI - Readers comment on "Herpes zoster ophthalmicus". PMID- 1455302 TI - Posterior capsule opacification. AB - A complication of extracapsular cataract extraction with or without posterior chamber intraocular lens (PC-IOL) implantation is posterior capsule opacification. This condition is usually secondary to a proliferation and migration of residual lens epithelial cells. Opacification may be reduced by atraumatic surgery and thorough cortical clean-up. Clinical, pathological and experimental studies have shown that use of hydrodissection, the continuous curvilinear capsulorhexis and specific IOL designs may help reduce the incidence of this complication. Capsular-fixated, one-piece all-polymethylmethacrylate PC IOLs with a C-shaped loop configuration and a posterior convexity of the optic are effective. Polymethylmethacrylate loops that retain "memory" create a symmetric, radial stretch on the posterior capsule after in-the-bag placement, leading to a more complete contact between the posterior surface of the IOL optic and the taut capsule. This may help form a barrier against central migration of epithelial cells into the visual axis. Various pharmacological and immunological methods are being investigated but conclusive data on these modalities are not yet available. PMID- 1455303 TI - Prospective study of the use of intraarterial secretin injection and portal venous sampling to localize duodenal gastrinomas. AB - BACKGROUND: Duodenal gastrinomas producing Zollinger-Ellison syndrome (ZES) are rarely imaged on preoperative studies. Measurement of serum gastrin levels by transhepatic portal venous sampling (PVS) or by sampling from hepatic veins after intraarterial secretin injection have been advocated as useful tests to identify these tumors before operation. METHODS: As part of a prospective study, selective intraarterial secretin injection has been performed in 36 consecutive patients with ZES, PVS has been performed in 30 of these patients, and the results have been compared. RESULTS: Gastrinomas were found at laparotomy in 33 of 36 patients (92%). Duodenal tumors were found in 18 patients (50%). The remaining patients had liver, pancreatic, or nodal disease (n = 15). Thirty-two of 36 patients (89%) had positive results with intraarterial secretin injection study, whereas 18 of 30 (60%) had a positive PVS gradient (p = 0.02, Fisher's exact test). The most common positive gradient with intraarterial secretin injection was found with injections of the gastroduodenal artery, and the most common positive gradient with PVS was found in the inferior pancreaticoduodenal (IPDV) or superior pancreaticoduodenal vein (SPDV). Fourteen of 18 (78%) patients with duodenal gastrinomas had a positive GDA injection, whereas five of 18 (28%) without duodenal tumors had a positive GDA injection (p = 0.006). Five of 16 patients with duodenal gastrinomas had a positive gradient in the IPDV or SPDV, whereas four of 14 without duodenal tumors had a positive gradient in the IPDV or SPDV (not significant). CONCLUSIONS: Intraarterial secretin injection is more sensitive than PVS at localizing duodenal gastrinomas and should replace PVS in patients with ZES and occult tumors. PMID- 1455304 TI - Occult functioning insulinomas: which localizing studies are indicated? AB - BACKGROUND: An occult insulinoma refers to a biochemically proven tumor with an anatomic site that remains indeterminate before operation. The amount of radiologic localization for such patients is debatable. METHODS: Sixty-five patients with sporadic insulinomas were surgically treated at the Mayo Clinic between January 1980 and December 1990. True occult tumors were present in 31% of these patients (n = 20). Thirty-eight negative preoperative localization studies were performed, with 10 patients undergoing more than one study. A benign adenoma was found in 19 patients when they underwent exploratory operation, whereas one patient had malignant disease with hepatic metastases. Thirteen patients underwent intraoperative ultrasonography with a 7.5 MHz real-time high-resolution transducer. RESULTS: Solitary lesions were successfully removed either by enucleation or by distal pancreatectomy in all 19 patients with benign disease. CONCLUSIONS: This high success rate in the management of occult insulinomas suggests that extensive preoperative radiologic investigation is neither indicated nor cost-effective. PMID- 1455305 TI - Prospective study of aggressive resection of metastatic pancreatic endocrine tumors. AB - BACKGROUND: Because metastatic pancreatic endocrine tumors (MPET) have a poor prognosis, 17 patients with potentially resectable MPET were prospectively studied to define the efficacy of aggressive resection. METHODS: Patients underwent resection when the full extent of MPET was deemed operable after imaging studies were obtained. Two patients underwent three reoperations for recurrent tumor. RESULTS: MPET were completely excised in 16 of 20 cases by major resections of liver, viscera, and nodes, with no operative mortality. Survival was 87% at 2 years and 79% at 5 years with mean follow-up of 3.2 years. Median imaging disease-free interval was 1.8 years, and four of 17 patients remain biochemically cured. After aggressive resection patients with MPET limited in extent had higher survival than patients with extensive MPET (p < 0.019). In a nonrandomized cohort of 25 patients with inoperable tumor, survival was 60% at 2 years and 28% at 5 years. CONCLUSIONS: In select patients MPET can be resected safely with a favorable outcome; most patients will experience recurrence, but some may be cured. Resection of extensive MPET does not appear to improve survival. Resection of limited MPET should be considered as life-extending and potentially curative therapy. PMID- 1455306 TI - A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas. AB - BACKGROUND: Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas. METHODS: Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 micrograms subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded. RESULTS: Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different. CONCLUSIONS: Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas. PMID- 1455307 TI - Neuroendocrine carcinomas of the stomach: a clinicopathologic evaluation. AB - BACKGROUND: The purpose of this study was to determine by immunocytochemistry the relative incidence and clinicopathologic characteristics of neuroendocrine carcinomas of the stomach. METHODS: Sections from paraffin blocks from 81 patients who had undergone resection of carcinomas of the stomach were immunostained with a battery of neuroendocrine differentiation markers and with A 80, a marker of exocrine differentiation. The clinical and pathologic data of the 12 patients diagnosed with neuroendocrine carcinomas of the stomach were analyzed. RESULTS: The 10 men and two women ranged from 53 to 81 years of age (median, 69 years). Procedures performed included distal subtotal gastrectomy in eight patients and total gastrectomy in four patients. Pathologic stages were stage I, one patient; stage III, four patients; and stage IV, seven patients. Metastatic sites included regional nodes, 11 patients; liver, four patients; and bone, one patient. Adjunct treatment included multiagent chemotherapy plus radiotherapy, four patients; and only radiotherapy, one patient. Eleven patients died of disease 1 to 27 months after diagnosis with an overall median survival of 15 months. Three groups of neuroendocrine carcinomas were identified based on immunostaining patterns. These included pure neuroendocrine carcinomas, two patients; neuroendocrine carcinomas with occasional exocrine cells, three patients; and mixed neuroendocrine-exocrine carcinomas, seven patients. CONCLUSIONS: (1) The relative incidence of neuroendocrine differentiation in carcinomas of the stomach is higher than is generally recognized. (2) Neuroendocrine gastric carcinomas behave aggressively and display numerous structural and functional similarities with their colonic, extrahepatic biliary tract, and pulmonary counterparts. PMID- 1455308 TI - Bombesin stimulates growth of human gastrinoma. AB - BACKGROUND: We have previously reported the first establishment and characterization of a functioning human gastrinoma (PT) xenograft. Bombesin, the equivalent of the mammalian gastrin-releasing peptide, has trophic effects on normal and neoplastic tissues of the gastrointestinal tract; the effects of gut hormones on the growth of gastrinoma are not known. The purpose of this study was twofold: (1) to determine the presence of various gut peptides in PT and (2) to determine the effect of bombesin on the growth of PT xenografts. METHODS: PT tumors were examined for expression (mRNA and protein) of various gut peptides by Northern hybridization and immunohistochemistry. In addition, PT xenografts were implanted as 3 mm2 pieces bilaterally subcutaneously in athymic nude mice. Mice were divided into two groups to receive either bombesin (5 micrograms/kg) or saline administered as intraperitoneal injections every 8 hours. Tumor area was measured twice weekly until mice were sacrificed (day 28), when tumor and normal pancreas were removed, weighed, and assayed for DNA and protein content. RESULTS: Both mRNAs and peptides of gastrin and chromogranin A were present in PT tumors. Bombesin significantly stimulated growth of PT tumors from day 18 until mice were sacrificed (day 28). As expected, bombesin stimulated pancreatic growth. CONCLUSIONS: We have demonstrated for the first time that bombesin is a trophic hormone for gastrinoma. The unique cell line PT contains gastrin and chromogranin A and will be a useful model to define the biologic mechanisms controlling the growth of human gastrinomas. PMID- 1455309 TI - Family members of patients with sporadic medullary thyroid carcinoma must be screened for hereditary disease. AB - BACKGROUND: Medullary thyroid carcinoma (MTC), a tumor arising from calcitonin secreting C cells, appears in either a sporadic nonfamilial or a hereditary form as a component of a multiple endocrine neoplasia syndrome or familial non multiple endocrine neoplasia MTC. Screening kindred of a patient with familial MTC to detect MTC in the early curable state is standard practice. Opinions conflict about whether it is necessary to screen relatives of patients with apparently nonfamilial MTC to exclude hereditary disease or whether the clinicopathologic features can differentiate between the two forms. METHODS: Clinically well kindred of a patient with MTC that was histopathologically characteristic of the sporadic type were screened for hereditary disease by measurement of plasma levels of basal and stimulated calcitonin. RESULTS: Three of four immediate relatives tested positive for excessive calcitonin secretion and underwent thyroidectomy. All had C-cell hyperplasia, the premalignant phase of MTC. CONCLUSIONS: The patient with apparently sporadic (nonfamilial) MTC was clearly an index case of familial disease. We conclude that clinical presentation and histopathologic examination are not adequate to reliably exclude hereditary MTC. Until genetic markers are readily available to distinguish between sporadic and familial forms, biochemical screening should be done in primary relatives of all patients with newly detected MTC. PMID- 1455310 TI - Relationships of parathyroid hormone, parathyroid secretory protein, parathyroid hormone messenger RNA, parathyroid secretory protein mRNA, and replication in human parathyroid adenoma and secondary hyperplasia tissues and cultures. AB - BACKGROUND: The purpose of this study was to clarify the relationships of extractable and secreted parathyroid hormone (PTH) and parathyroid secretory protein (PSP) in human parathyroid tumors to PTH messenger RNA (mRNA), PSP mRNA, and cell replication. METHODS AND RESULTS: In tissue cultures of seven adenomas and five secondary hyperplasias, we found a direct correlation for secreted PTH versus PSP for both adenomas and secondary hyperplasias. Secreted PTH:PSP was elevated for adenomas (11:1) compared to that of secondary hyperplasias (2:1), and adenomas secreted significantly more PTH and PSP than did secondary hyperplasias. In extracts of eight adenomas and six secondary hyperplasias, the ratio of PTH:PSP was unexpectedly low (2:1) and similar for both adenomas and secondary hyperplasias. The ratio of extractable PTH mRNA:PSP mRNA was extremely low for both adenomas (1:7) and for secondary hyperplasias (1:5). Flow cytometry indicated that percent replication was inversely correlated with PTH mRNA and PSP mRNA. CONCLUSIONS: Increased PTH secretion by adenomas cannot be attributed to increased biosynthetic capacity because it is less than expected. Hypersecretion of PTH by adenomas and coincident marked reductions in PTH mRNA suggest either a defect in cytoplasmic storage of PTH or impairment of normal posttranslational degradation of PTH. As parathyroid tumor cells increase replication, PTH mRNA is reduced. Possible explanations for this include decreased PTH gene transcription or decreased mRNA half-life. PMID- 1455311 TI - The effect of cryopreservation on cell viability and hormone secretion in human parathyroid tissue. AB - BACKGROUND: To explain the decreased success of cryopreserved versus fresh parathyroid autotransplants, we investigated the effect of cryopreservation on parathyroid function. METHODS: Parathyroid cryopreserved tissue from surgical specimens of 18 patients was analyzed in a comparative fashion with 10 fresh abnormal glands. Cell viability was evaluated by a double-fluorescence technique, and parathyroid hormone secretion was detected from individually dispersed parathyroid cells with the reverse hemolytic plaque assay. The plaque area reflected the amount of parathyroid hormone secreted by each cell, and the percentage of plaque-forming cells represented the number of secreting cells. Feedback regulatory mechanisms remained intact for both fresh and cryopreserved tissue as shown over a wide range of calcium concentrations. RESULTS: The percentage of viable cells from fresh and cryopreserved tissue was always in excess of 88%. No significant difference was noted in the percentage of plaque forming cells nor the amount of hormone released per individual cell comparing fresh and cryopreserved glands (6 months to 2 years). Specifically, at physiologic calcium concentrations no significant differences existed in the secretory behavior between fresh and cryopreserved tissue. CONCLUSIONS: Without showing decreased viability or parathyroid hormone secretion after cryopreservation, the cause of graft failure in cryopreserved tissue still remains unknown. PMID- 1455312 TI - Role of the oral calcium-loading test with measurement of intact parathyroid hormone in the diagnosis of symptomatic subtle primary hyperparathyroidism. AB - BACKGROUND: This study was designed to assess the diagnostic value of the oral calcium tolerance test with measurement of intact parathyroid hormone by the immunoradiometric assay (IRMA PTH) in the diagnosis of primary hyperparathyroidism in patients with symptoms who have minimal, intermittent, or no elevation of the levels of total calcium and/or intact PTH. METHODS: After baseline levels of IRMA PTH and total calcium were measured, an oral calcium load of 1000 mg elemental calcium was administered to 10 patients with hyperparathyroidism and 18 normal control subjects. Total calcium and IRMA PTH levels were measured at 30, 60, and 120 minutes after the oral calcium load was administered. RESULTS: The mean suppression of the baseline level of IRMA PTH in the patients with hyperparathyroidism was 83.7% +/- 6.5% (mean +/- 1 SEM), but the levels of the normal control subjects fell significantly (p < 0.05) lower to 58.8% +/- 3.7% (mean +/- 1 SEM). CONCLUSIONS: This study suggests that the oral calcium tolerance test may be a valuable adjunct in confirming the diagnosis of primary hyperparathyroidism in patients with symptoms who have minimal, intermittent, or no elevation of the levels of total calcium and/or IRMA PTH: PMID- 1455313 TI - Prospective evaluation of the efficacy of technetium 99m sestamibi and iodine 123 radionuclide imaging of abnormal parathyroid glands. AB - BACKGROUND: Technetium 99m sestamibi is an isonitrile radionuclide imaging agent that, when used with subtraction iodine 123 thyroid scans, has the potential for imaging abnormal parathyroid glands. METHODS: We prospectively evaluated 20 patients with hyperparathyroidism to study the efficacy of Tc 99m sestamibi and 123I subtraction radionuclide scanning for the imaging of abnormal parathyroid glands. All patients underwent neck exploration and histologic confirmation of all parathyroid glands identified. RESULTS: The solitary adenomas in 11 of 16 patients with primary hyperparathyroidism were localized with sestamibi scans. The scans in four of five patients with diffuse parathyroid hyperplasia showed bilateral localization consistent with enlarged glands. The fifth patient previously underwent a subtotal parathyroidectomy, and a fifth supernumerary gland was localized with the sestamibi scan. Four patients had hyperparathyroidism related to kidney disease. Three of these had bilateral localization of enlarged glands. The fourth patient had undergone two previous operations, and a fifth supernumerary gland was localized with the sestamibi scan. CONCLUSIONS: The preliminary data indicate that Tc 99m sestamibi in combination with 123I radionuclide scanning may be useful in the preoperative localization of abnormal parathyroid glands. This technique localized all of the solitary adenomas that were subsequently resected, and in two reoperative cases it identified the remaining solitary gland causing persistent hypercalcemia. PMID- 1455314 TI - Long-term effects of parathyroid operation on serum calcium and parathyroid hormone values in sporadic primary hyperparathyroidism. AB - BACKGROUND: This study investigates 410 persons (median age, 67 years) who underwent parathyroid operation for sporadic primary hyperparathyroidism 6 to 32 years (mean, 14.2 years) before 1991. METHODS: Patient records and operative specimens were scrutinized, the patients answered a questionnaire, and fasting serum samples were analyzed for calcium, albumin, creatinine, and intact parathyroid hormone (PTH) values. RESULTS: After primary parathyroid operations were performed with a conservative surgical approach, persistent and recurrent hypercalcemia were noticed in 3.7% and 1.7% of patients, respectively, whereas 4.7% of patients required vitamin D substitution or had essentially mild hypocalcemia. The PTH values were generally increased in patients with postoperative hyperparathyroidism, low in those with vitamin D substitution, and normal to elevated in the patients with hypocalcemia and in those with postoperative normocalcemia. The mean serum creatinine concentration was just below the upper reference range and correlated strongly with serum PTH value. No significant differences in serum PTH values were present between the normocalcemic patients and matched control patients after operation (n = 107), but the patients who underwent operation exhibited greater variation in the PTH concentration. CONCLUSIONS: The results substantiate the efficacy of parathyroid operation in sporadic primary hyperparathyroidism. Biochemical derangements compatible with secondary hyperparathyroidism may evolve during long-term follow up and contribute to decreases in serum calcium values and increases in serum PTH values of these patients. PMID- 1455315 TI - Follicular thyroid carcinoma with capsular invasion alone: a nonthreatening malignancy. AB - BACKGROUND: The study was designed to determine whether invasion of the tumor capsule, in the absence of vascular invasion (VI), was significant in predicting cause-specific mortality in follicular thyroid carcinoma (FTC). METHODS: Seventy two patients with FTC were treated by us during 1971 through 1985. In 65 cases the tumors could be classified as either showing capsular invasion (CI) alone (20) or VI, with or without CI, (45). Median follow-up of 45 survivors was 11 years; 12 patients died of FTC. RESULTS: The 10-year occurrence rates for cause specific mortality and distant metastases were 28% and 19%, respectively, for patients with VI. Comparable rates for the patients with CI were 0% (p = 0.019) and 0% (p = 0.052), respectively. By univariate analysis, higher rates of cause specific mortality were significantly associated with distant metastases at diagnosis (p < 0.0001), the presence of VI (p = 0.019), and moderate or marked microinvasion (p = 0.019). In stepwise multivariate analyses, only distant metastases at diagnosis had independent prognostic significance (p < 0.0001) in the prediction of cause-specific mortality. In a Cox model, adjusting for distant metastases at diagnosis, the presence of VI was of borderline significance (p = 0.06) in predicting cause-specific mortality. CONCLUSIONS: FTC, diagnosed on the basis of CI alone, did not result in either distant metastases or cancer-related death. The dominant determinant of cause-specific mortality was the presence of distant metastases at diagnosis. PMID- 1455316 TI - Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. AB - BACKGROUND: The study aims were to characterize patients with papillary thyroid microcarcinoma and to provide data on outcome after surgical therapy. METHODS: Five hundred thirty-five patients with papillary microcarcinoma had initial treatment at Mayo Clinic from 1940 to 1989. Follow-up extended to 48 years. Median follow-up time for 400 survivors was 16 years. Recurrence and mortality details were derived from a computerized cancer database. RESULTS: Median tumor size was 8 mm. Ninety-nine percent of tumors were histologic grade 1; 98% were not locally invasive. Thirty-two percent of patients had nodal metastases at examination. TNM stages were I in 485 patients (91%), III in 49 patients (9%), and IV in one patient (0.2%). Ninety-one percent of patients underwent bilateral lobar resection. Tumor resection was incomplete in three cases (0.6%). Radioiodine remnant ablation was performed in 55 patients (10%). All-causes survival did not differ from expected; two patients (0.4%) died of papillary microcarcinoma. Twenty-year tumor recurrence rate was 6%. Higher recurrence rates were seen either with node-positive patients (p < 0.0001) or after unilateral lobectomy (p < 0.0001). Recurrence rates did not appear to be significantly altered by total thyroidectomy (p = 0.44) or radioiodine remnant ablation in node positive patients (p = 0.99). CONCLUSIONS: These results reaffirm that papillary microcarcinoma has an excellent prognosis if managed initially by bilateral lobar resection. Routine radioiodine remnant ablation is not indicated. PMID- 1455317 TI - Completion thyroidectomy: a critical appraisal. AB - BACKGROUND: Completion thyroidectomy can most accurately be described as reexploration of the neck to remove the contralateral thyroid lobe. This procedure has commonly been performed when the histopathologic condition of the ipsilateral thyroid lobe reveals papillary or follicular carcinoma of the thyroid. Because of a definitely increased risk of complications with completion thyroidectomy, avoiding its routine use is important. The purpose of this paper is to define the specific indications for completion thyroidectomy. METHODS: Over the past 9 years, we have performed 400 thyroidectomies; the patients ranged in age from 18 to 88 years. Although we have routinely used preoperative needle biopsy and intraoperative frozen section, decisions regarding the extent of thyroidectomy have been based on the gross findings at operation, taking into consideration such prognostic factors as patient age, tumor grade and size, the presence of extracapsular spread or distant metastasis, and associated risk factors. The minimal procedure for solitary thyroid nodule has been lobectomy with isthmusectomy. If the contralateral lobe is grossly normal, lobectomy with isthmusectomy has also been the maximal operation in most of patients. Very few specific indications exist for removal of the opposite lobe. RESULTS: Only three patients underwent completion thyroidectomy. All three patients had aggressive follicular carcinoma requiring radioactive iodine ablation, and all were referred after the initial surgery. We have not performed completion thyroidectomy on any of the patients on whom we initially operated. CONCLUSIONS: The most common indication considered for completion thyroidectomy is a frozen section diagnosis of a benign follicular adenoma that is subsequently changed on permanent pathologic condition to follicular carcinoma based on the presence of capsular and/or vascular invasion. However, if minimal invasion has occurred, no difference exists in survival related to the extent of the thyroidectomy. Local recurrence in the contralateral lobe occurs in less than 10% of the time. Because completion thyroidectomy carries more risks, it should be avoided in most patients when possible. The definitive decision should be made during the initial operation based on gross findings, prognostic factors, and frozen section, and this plan should only be changed to mandate completion thyroidectomy in select circumstances. PMID- 1455318 TI - Addition of nuclear DNA content to the AMES risk-group classification for papillary thyroid cancer. AB - BACKGROUND: The purpose of this study was to prospectively assess whether nuclear DNA content added prognostic value to existing risk factors in patients with papillary thyroid cancer. METHODS: Nuclear DNA content was measured both on the fine needle aspiration material and the surgical specimen in 73 patients with primary or recurrent papillary thyroid cancer. We modified the existing age of patient, presence of distant metastases, extent and size of the tumor (AMES) risk group classification to include DNA ploidy with AMES (DAMES). Patients with euploid tumors that were AMES low risk were considered to be DAMES low risk; patients with euploid tumors that were AMES high risk became intermediate risk, and patients with aneuploid tumors that were AMES high risk became DAMES high risk. RESULTS: Forty-eight patients were in the DAMES low-risk group. Recurrences and/or distant metastases developed in only four (8%) of these patients. Twenty two patients were in the DAMES intermediate-risk group. Twelve (55%) of the intermediate-risk group had residual, recurrent, or distant metastatic disease, with one death from cancer at 120 months. Three patients were in the DAMES high risk group. Distant metastases developed in all three patients, who died within 24 months from thyroid cancer. A statistically significant difference existed in the development of recurrence/metastases or death from cancer in the DAMES high risk group compared with the other risk groups combined. CONCLUSIONS: Nuclear DNA content adds prognostic value to the existing AMES risk-group classification. Because DNA analysis on fine needle aspiration correlated well with the surgical specimen DNA analysis, this modified classification can be used perioperatively to further individualize the treatment of patients with papillary thyroid cancer. PMID- 1455319 TI - Percutaneous intranodular ethanol injection for treatment of autonomously functioning thyroid nodules. AB - BACKGROUND: The aim of the study is the assessment of percutaneous intranodular ethanol injection (PNEI) as an alternative therapeutic procedure to classic surgery and radioiodine administration in autonomously functioning thyroid nodule treatment. METHODS: Thirty-seven patients with hot nodules (18 pretoxic and 19 toxic) have been treated by means of PNEI under ultrasonographic guide. Ninety five percent ethanol in a mean dose of 25 ml has been used. RESULTS: Nearly 80% of the patients showed normalization of thyroid-stimulating hormone levels and a complete recovery of extranodular tissue at scintiscan. All nodules decreased strikingly in size, many becoming undetectable. Mild and transient side effects were seen in 9% of the patients. CONCLUSIONS: PNEI seems to be a feasible procedure on outpatients. It is safe when performed by a well-trained staff using ultrasonographic control. It may be carried out at any age and in patients at risk for surgery. PNEI can be considered a useful alternative to surgery and radioiodine administration in all autonomously functioning thyroid nodules and particularly in pretoxic nodules. PMID- 1455320 TI - Treatment of toxic solitary thyroid nodules: surgery versus radioactive iodine. AB - BACKGROUND: Because of controversy about the correct treatment of toxic solitary thyroid nodules, we reviewed our experience. METHODS: We retrospectively studied 32 patients (24 women and 8 men) with solitary toxic thyroid nodules who were treated at our institution (1970 to 1985). RESULTS: Median values were as follows: age of patients at initial treatment, 67.6 years (range, 18.9 to 86.2 years); follow-up, 3.8 years; largest diameter of nodules, 3.3 cm (range, 1.5 to 6 cm); and 131I uptake at 24 hours, 31% (range, 7% to 54%). Nine patients had surgical treatment: subtotal thyroid lobectomy in six patients and subtotal thyroidectomy in three patients. Hypothyroidism developed in two of these nine patients (22%) 9 months after operation. No surgical complications occurred. No surgically treated patient had nodule recurrence or required re-treatment. Twenty three patients were treated with radioactive iodine (median dose, 29.1 mCi; range, 19.7 to 100 mCi). Two of them were re-treated: one patient underwent thyroid lobectomy because of concern about the nodule, and one patient was re treated with radioactive iodine because of persistent toxicity. Hypothyroidism was detected in eight of the 23 patients (35%) treated with radioactive iodine after treatment. Of the 16 patients treated with radioactive iodine with at least 1 year follow-up and no re-treatment, nine (56.3%) have had complete regression of the nodule. CONCLUSIONS: Surgical excision of solitary toxic thyroid nodules would appear to be the treatment of choice. PMID- 1455321 TI - An eleven-year experience with adrenocortical carcinoma. AB - BACKGROUND: Key issues in the treatment of adrenocortical carcinoma are the value of adjuvant therapy, the value of reoperation, and the search for effective chemotherapeutic agents. The present series was reviewed to evaluate these issues. METHODS: We present a retrospective series of 73 patients with adrenocortical carcinoma treated at a single institution. RESULTS: Twenty patients had carcinomas that were unresectable, and 53 patients underwent complete resections. Ten patients received adjuvant therapy (mitotane, seven patients; radiation, three patients). Forty-five (85%) patients had recurrence, including all who received adjuvant therapy. Mean disease-free intervals for those who did and did not receive adjuvant therapy were equivalent at 2.4 years. Nineteen patients with recurrent disease received chemotherapy, and 26 patients underwent 51 reoperations to resect recurrent and metastatic disease. The overall 5-year survival rate, which was 35%, was 47% for patients with complete resection. Stage and resectability were prognostic factors. Mean survival time for patients with recurrent disease treated medically was 19 months compared with 56 months for patients who underwent reoperation. Mitotane had a 24% partial response rate. Other chemotherapeutic agents were ineffective. CONCLUSIONS: We conclude that an aggressive surgical approach to recurrent and metastatic disease should be adopted and that patients should be resected free of disease whenever possible. Currently no effective chemotherapy exists, and the value of adjuvant therapy remains unproved. PMID- 1455322 TI - Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery. AB - BACKGROUND: Because of the rarity of adrenocortical carcinoma, survival rates and prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine Surgery was to evaluate these factors in all patients treated during a 12-year period by its members. METHODS: One hundred fifty-six patients (95 women, 61 men) with a mean age of 47 years were included. Functional symptoms were found in 52% of patients, and hormonal studies revealed secreting tumors in 62% of cases. Ninety-four percent of the patients underwent resection of the adrenal tumor, and 20% of them had extensive resection because of invasive cancers. Complete resection was achieved in 127 patients (81%) and incomplete resection in 29 patients. Mean tumor weight was 714 gm (range, 12 to 4750 gm), and the mean diameter was 12 cm (range, 3 to 30 cm). The results of the tumor staging were stage I, eight patients (5%); stage II (local disease), 75 patients (48%); stage III (locoregional disease), 39 patients (25%); and stage IV (metastases), 34 patients (22%). RESULTS: The 5-year actuarial survival rates were 34% overall, 42% in curative group, 53% in local cancer group, 24% in regional disease group, and 27% in the reoperated group. One year actuarial survival rate of the palliative group was 9% (median survival, 6 months). Multivariate analysis showed that better prognosis occurred in patients younger than 35 years of age (p = 0.01) and in patients with androgen-secreting tumors, precursor-secreting tumors, or nonsecreting tumors (p = 0.003). Mitotane improved the survival rate only in patients with metastases who received it after operation (vs non-mitotane-treated patients [p < 0.05]). CONCLUSIONS: In this study age, extent of disease, aspect of the surgical resection, and type of hormonal secretion influenced survival. PMID- 1455323 TI - Risk factors associated with postoperative persistent hypertension in patients with primary aldosteronism. AB - BACKGROUND: Unilateral adrenalectomy was performed in 63 patients with primary aldosteronism. During a mean follow-up time of 4.1 years, none of the patients showed recurrence of hyperaldosteronism. However, 24 patients (38%) had persistent hypertension. The purpose of this study was to determine factors responsible for postoperative persistent hypertension. METHODS: A stepwise multivariate logistic regression analysis was performed to assess the combined predictive effects of the clinicopathologic variables. RESULTS: Age, sex, and pathologic findings were the best predictive factors of postoperative persistent hypertension. For a patient aged 50 years or more, the odds of persisting hypertension are 10.6:1, compared with those of a patient under 40 years of age. A male patient appears to have a greater chance of hypertension than a female patient; the odds ratio is 5.9:1. Persistent hypertension develops in patients with multiple adenomas or with an adenoma associated with macronodules more frequently than in those patients with a solitary adenoma; the odds ratio is 8.1. CONCLUSIONS: This study suggests that early surgical intervention at a younger age results in a more favorable outcome for patients with primary aldosteronism. The presence of macronodules in association with an adenoma is a cautious predictor of persistent hypertension after adrenalectomy. PMID- 1455324 TI - Acupuncture and occlusal splint therapy in the treatment of craniomandibular disorders. Part I. A comparative study. AB - One hundred and ten patients, 23 males and 87 females, participated in a comparative study of the effect of acupuncture and occlusal splint therapy. All the patients exhibited signs and symptoms of craniomandibular disorders (CMD) and had had pain for more than six months. The participants were randomly assigned to three groups; acupuncture treatment, occlusal splint therapy or control. The patients were evaluated before and immediately after treatment/control time. Ten different subjective and/or clinical assessment variables were used in the evaluation of the treatment effects. Both acupuncture and occlusal splint therapy reduced the symptoms as compared with the control group in which the symptoms remained essentially unchanged. In this short-term study, acupuncture gave better subjective results (p < 0.001) than the occlusal splint therapy. PMID- 1455325 TI - Dental caries in a group of 15 to 16-year-olds from Goteborg. Part I. AB - 301 adolescents aged 15 to 16 years (158 girls and 143 boys) were examined for caries under standardized conditions during the fall and spring terms of 1987/88. Clinical examinations, performed by two calibrated examiners were supplemented with posterior bite-wing radiographs which were assessed by one of the examiners. The mean DFT and DFS scores (incipient lesions included) were 9.8 and 19.4, respectively. The mean DFS score (dentin lesions+restorations) was 6.4. On average 1.9 surfaces had frank cavities or recurrent lesions and 13 surfaces had incipient lesions. Occlusal surfaces contributed 75%, approximal 21% and bucco linqual 4% to the manifest component of the DFS score (4.8, 1.4 and 0.2 surfaces, respectively). 3% of the incipient lesions were found occlusally, 51% approximally and 46% bucco-linqually (0.4, 6.6 and 5.9 surfaces, respectively). Only 3% of the participants were completely free from caries, whereas 9% had no dentin lesions or restorations. 15% of the subjects with the highest caries prevalence averaged 15.8 dentin lesions or restorations. A tendency towards polarization of low and high caries prevalence groups was observed. Totally 91% of the individuals had occlusal caries, 82% approximal and 76% bucco-lingual, whereas dentin lesions or restorations had 88%, 42% and 14%, respectively. PMID- 1455327 TI - Root development of the lower third molar and its relation to chronological age. AB - Methods based on radiological, distinguishable stages of tooth formation can be used to estimate chronological age in young persons. The best precision and accuracy of these methods of age estimation is obtained when many teeth are under development and when the individual growth rate is rapid. That is during early years-in childhood. After an age of about 14 years it becomes more difficult since all permanent teeth but the wisdom teeth have completed their development and only these remain to be used for age estimation. The aim of this study was to examine the radiological development of the root of the mandibular third molar and to explore its usefulness in age estimation. Also the differences between two independent observers were studied. The observers classified the development of the mandibular third molars, as seen in a panoramic radiograph, into seven defined stages. The two observers agreed in about 84% of the cases in their registration of the different stages, but a significant difference was found between the observers. The mineralisation of the third molar's root was found to start at the age of 15 years and the root was fully formed at about 20 years. Some minor differences were found between sexes in the time sequence of the mineralisation. The study also shows that there is a rather low precision in the age estimation with the method used. In general, a standard deviation of about 1 to 2 years was found around the mean age of the different developmental stages. PMID- 1455326 TI - Pain control after third molar surgery--a comparative study of ibuprofen (Ibumetin) and a paracetamol/codeine combination (Citodon). AB - Two analgesics commonly used in oral surgery, ibuprofen (Ibumetin) and a paracetamol/codeine combination (Citodon) have been compared in a single-blind multi-centre trial after third molar surgery. The study comprised 120 patients, 60 in each treatment group. The profiles of postoperative pain in the two groups were similar from the first postoperative day, but Ibumetin was better pain reliever on the day of surgery. The profiles of postoperative swelling and trismus had the same general course, but patients taking Ibumetin reported lower scores for these variables during the whole postoperative period. Citodon induced significantly more side-effects than Ibumetin. PMID- 1455329 TI - [Difficult and important to document. Interview by Kirsten Bjornsson]. PMID- 1455328 TI - A clinical evaluation of adhesively luted ceramic inlays. A two year follow-up study. AB - Fired porcelain inlays were cemented in class II cavities with either a dual cured composite or a glass ionomer luting cement. Clinically evaluation according to modified USPHS criteria was done at baseline and after 6, 12 and 24 months. Inlays bonded with the composite resin showed a 2% failure rate, while 15% of the inlays cemented with the glass ionomer were lost or fractured during the evaluation period. The failures were in most cases due to an adhesive bond failure at the cement-porcelain interface. PMID- 1455330 TI - [Health--a common concern]. PMID- 1455331 TI - [Being together is better than medicine]. PMID- 1455332 TI - [Professional togetherness. Interview by Grethe Kjaergaard]. PMID- 1455333 TI - [Citizens' health. Interview by Grethe Kjaergaard]. PMID- 1455336 TI - [Congress 1992. Occupational lesions tell some of it]. PMID- 1455334 TI - [Across the Atlantic. Interview by Grethe Kjaergaard]. PMID- 1455335 TI - [Visions and reality. Interview by Grethe Kjaergaard]. PMID- 1455337 TI - [Ombudsman representatives. Powerlessness is the most dangerous. Interview by Soren Palsbo]. PMID- 1455338 TI - [First aid. Casualty ward as scrap-heap]. PMID- 1455339 TI - [Illness--nurse with diabetes. Interview by Stig Thomasen]. PMID- 1455340 TI - [Colleagues for sale]. PMID- 1455341 TI - [Education--the students must learn how to study]. PMID- 1455342 TI - [Nursing care--cancer patients miss contact]. PMID- 1455343 TI - [Congress 1992. The weakest pay the price]. PMID- 1455344 TI - [Congress 1992. We are in a strong position]. PMID- 1455345 TI - [We ought to applaud here. Congress 1992]. PMID- 1455346 TI - [Negotiations '93. Invitation to a discussion about wage claims]. PMID- 1455347 TI - [Nursing narratives--the silent knowledge]. PMID- 1455348 TI - [Health project. Health books]. PMID- 1455349 TI - [How do we handle our democracy. Congress 1992]. PMID- 1455350 TI - [Competition in working conditions. Congress 1992]. PMID- 1455351 TI - [Incomprehensible attitude to local wages. Congress 1992]. PMID- 1455352 TI - [Parapulpal pins for plastic constructions]. PMID- 1455353 TI - [Soft tissue models. 1. Gingiva imitation in soft permanent acrylic]. PMID- 1455354 TI - [Thermodisinfection and sterilization of various rotating instruments]. PMID- 1455355 TI - [Plastic cement strength and color stability]. PMID- 1455356 TI - [Ceramic brackets]. AB - Because of the many drawbacks of the hard and brittle material, ceramic brackets should not be used uncritically for orthodontic treatments. If ceramic brackets are used, the following guidelines should be observed: 1. If large and complicated tooth movements are involved, conventional bracket systems should be considered. 2. Occlusion on ceramic brackets is to be avoided. 3. Sharp instruments should be used with extreme care to avoid scratching the ceramic surface. Metal ligatures must not be used. 4. The length of the treatment is extended, probably because of the increased friction. 5. The problems connected with removing the brackets have not yet been solved. Be particularly careful of weakened teeth. 6. Esthetically, ceramic brackets function satisfactorily, but transparent elastic ligatures do not. They rapidly become discoloured and need frequent replacement. Nor are there as yet any "invisible arch wires", apart from some few, extremely flexible "white" arch wires. The ceramic bracket has no doubt come to stay, but there have been many difficulties in the "running-in" period, and the problems are far from solved yet. New ceramic brackets are coming onto the market all the time, and only future clinical studies can show whether they will become a genuine alternative to the conventional bracket. PMID- 1455358 TI - [Soft tissue models. 2. Gingiva imitation with polyether--or silicone bases]. PMID- 1455359 TI - [Bilateral eminectomy in the surgical management of recurrent jaw luxation]. AB - The different types of luxations in the temporomandibular joint and their management are discussed. The bilateral eminectomia a.m. Myrhaug is described, and the results from our Department are presented. Seven patients have been operated, and all are relieved of their disease and free from pain. The patients are happy with the operations and there have been no postoperative complications. All the patients would recommend this type of operation to others in a similar situation. PMID- 1455357 TI - [Dislocation of mandibular condyle into middle cranial fossa]. AB - A case of dislocation of the mandibular condyle into the middle cranial fossa is presented. The patient was a 8-year-old girl. Immediate conservative reposition was performed successfully with an intermaxillary fixation for two weeks. Two years after the accident her dental occlusion had remained stable, although there was a slight limitation in opening. Based on the present case and previous case reports it is concluded that early diagnosis and treatment is important. Manual reduction and fixation should be the first choice of treatment. The risk of intracranial complications necessitates a close cooperation with a neurosurgeon. Follow-up studies have revealed that most of the patients develop laterognatism and/or limited movements of the mandible. PMID- 1455360 TI - [The clinico-immunological characteristics of central nervous system involvement in systemic lupus erythematosus: the relationship with antibodies to cardiolipin]. AB - As many as 30 patients suffering from systemic lupus erythematosus (SLE) with the clinical signs of central nervous system derangement were examined. The mean age of the patients was 31.1 years. Using EIA, antibodies against cardiolipin (a-CL) were detected in 21 patients (70%). A-CL were revealed in all the patients with cerebral circulation impairment (CCI), choreic hyperkinesis, and convulsive syndrome. A-CL were discovered in 12 out of 18 SLE patients suffering from migraine-like headaches and in 4 out of 5 patients with mental disorders. Antibodies reacting with cardiolipin were mostly represented by the IgM isotype (80%) whereas a-CL-IgG were only identified in 13% of the patients, being associated in all the cases with a-CL-IgM. The high level of a-CL-IgG in blood serum was recorded in patients with the gravest patterns of nervous system derangement: CCI, occlusion of the retinal artery, psycho-organic and convulsive syndromes. All these patients demonstrated generalized reticular livedo. The high levels of a-CL-IgM were observed in SLE patients with choreic hyperkinesis and migraine-like headaches. Thus, the studies made it possible to trace the relationship between the development of certain neurological disorders (CCI, chorea, convulsive syndrome) in SLE patients and a-CL. PMID- 1455361 TI - [The use of Capoten in systemic scleroderma]. AB - Experience gained with the use of captopril has been summarized in 5 patients with sclerodermic renal crisis (true sclerodermic kidney) as well as the results of the double blind clinical trial of captopril in 16 patients with Raynaud's syndrome. Captopril given for a long time in the dose 75-150 mg to the patients with true sclerodermic kidney turned out effective which showed up by a decline and stabilization of arterial pressure, decrease of the intensity of azotemia and headaches, and stabilization of renal function. No convincing data have been obtained, that may confirm a beneficial effect of captopril on Raynaud's syndrome. The drug was applied in a dose of 37.5 mg for 2 weeks. PMID- 1455362 TI - [Joint hypermobility--100 years after Chernogubov]. PMID- 1455363 TI - [Spondylarthritis ankylopoietica and HLA-B27]. AB - There is a strict association between HLA-B27 and a group of spondylarthropathies, especially with ankylosing spondylarthritis (AS). The causes of the association remain obscure, different hypotheses are regarded. There is an interaction between B27 and bacteria. However, the etiological and pathogenetic roles played by any of them in AS cannot be regarded as proved. B27 is an important genetic factor in the disease expression. It is implicated in the pathogenesis, being undoubtedly a risk factor. At the same time it cannot be excluded that B27 is only one of the genes, predisposed to the disease. From the practical standpoint, it is important that the I degree kinship relatives of AS patients, males in particular, having HLA-B27 may be subjected to prophylactic medical examinations. PMID- 1455364 TI - [The action of low-intensity laser radiation on the immune system]. PMID- 1455365 TI - [Hemodynamic changes in disorders of the heart rhythm and conduction]. PMID- 1455366 TI - [Immunological disorders in different clinical variants of rheumatoid arthritis]. AB - The authors present the current data on the disorders of immune functions in patients suffering from rheumatoid arthritis (RA). Provide evidence for the pathogenetic heterogeneity of the known clinical patterns of RA, mainly seronegative and seropositive varieties, with special reference to the differences in the lowering of the activity of nonspecific T suppressors, to the influence of the factor of necrosis of alpha-tumor and alpha- and beta interferons on B lymphocyte proliferation, and to the effects of synovial exudate from seropositive and seronegative patients. Demonstrate the results of integral estimation of the disorders of several characteristics of the immune system in RA patients with the use of the image recognition program. It is concluded that the clinical polymorphism of RA is specified by the pathogenetic heterogeneity of the disease based on varieties of combined normal and altered functions of different components of the immune system. PMID- 1455367 TI - [The biochemical heterogeneity of rheumatoid arthritis]. AB - The content of cyclic nucleotides (cAMP and cGMP) in plasma (or blood), synovial fluid and neutrophils was measured in 151 patients suffering from rheumatoid arthritis (RA) as was the content of prostaglandins (E2 and F2 alpha), ACTH, hydrocortisone, antioxidant system enzymes (superoxide dismutase and catalase). Part of the patients were examined over time. Relative stability of certain characteristics (the content of hydrocortisone, neuropeptides, superoxide dismutase, and so forth) was established throughout a long time, irrespective of the process activity or treatment provided. It is concluded that every RA patient has a "weak" biochemical component of his own, reflecting the activity or power of one or another regulatory system. PMID- 1455368 TI - [Changes in the production of monokines and prostaglandin E2 by the peripheral blood monocytes in patients with different clinico-immunological variants of rheumatoid arthritis]. AB - As many as 39 patients aged 16-70 years with rheumatoid arthritis (RA) lasting 3 months to 20 years were examined. The diagnostic titers of rheumatoid factor were discovered in 23 patients. The control group was made up of 26 healthy subjects (donors). The activity of IL-1 in supernatants of peripheral blood monocytes (PBM) was measured by bioassay resting on co-stimulation of mouse thymocytes; quantitative determination of tumor necrosis factor-alpha (TNF-alpha) was made by ELISA, PGE2 was determined by RIA. As compared to the controls, the RA patients manifested an increase of the production of IL-1 beta, TNF-alpha and PGE2 of PBM, which rose with the disease activity. The RA patients demonstrated direct correlations between the level of IL-1 beta, TNF-alpha and PGE2 in supernatants of PBM, whereas the donors showed up a negative correlation between IL-1 beta activity and PGE2. PMID- 1455369 TI - [The prediction of thrombosis development in patients with systemic lupus erythematosus: the role of antibodies to cardiolipin]. AB - In patients with systemic lupus erythematosus (SLE), the synthesis of antibodies to cardiolipin (A-CL) is associated with the development of venous and arterial thromboses localized in minor and middle-sized vessels, in the venous system and capillaries. The determination of various A-CL isotypes may be used to predict thromboses in SLE patients. Overall 210 patients (185 women and 25 men) with a verified diagnosis of SLE were examined. The patients were not screened in accordance with some or other clinical signs of the antiphospholipid syndrome. The control group comprised 100 healthy subjects (donors). The IgG, IgA and IgM isotypes of A-CL were determined by ELISA. Sera of SLE patients showed an increase of the concentration of A-CL of both certain isotypes and their potential combinations. Among A-CL-positive patients, the IgG isotype of A-CL was detected in 75% of cases, the IgM isotype of A-CL in 61%, and the IgA isotype of A-CL in 36% of cases. Thrombotic complications were recorded in 19% of patients. They were induced by hyperproduction of the three combinations of the A-CL isotypes: A-CL IgM, IgM+IgA, and IgG+IgA+IgM. Patients whose sera contained A-CL of all three types at a time were most prone to thrombotic complications. It has turned out that the percentage of SLE patients with thromboses was higher than that of SLE patients without thromboses, starting from the definite A-CL concentration (21 GPL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455370 TI - [The dynamics of the basic statistical indices of rheumatic diseases in the Russian Federation]. PMID- 1455371 TI - [A comparative evaluation of combined immunocorrective therapy in rheumatoid arthritis with systemic manifestations (joint Soviet-Polish research)]. AB - Thirty-two patients with rheumatoid arthritis were included in the trial. Each of them was assigned to one of the 4 groups comparable by the main features. Each group entered 8 patients. Group 1 patients underwent hemosorption weekly for 3 weeks. After the second procedure cyclophosphamide was added at a single IV dose 1000 mg. After the third procedure the treatment was continued with methotrexate (7.5 mg, weekly). Group 2 began the treatment with methotrexate (7.5 mg, weekly). Group 3 received cyclophosphamide 200 mg IV twice a week 6 times and then 200 mg weekly orally till a total dose of 2 g. Group 4 received azathioprine in a daily dose 100 mg. The treatment with nonsteroidal antirheumatic drugs and corticosteroids was continued unchanged. After 6 months we did not see significant differences between the 4 groups. PMID- 1455372 TI - [The efficacy of basic therapy in rheumatoid arthritis with methotrexate]. AB - Overall 25 patients with rheumatoid arthritis received methotrexate as basic therapy in a weekly dose of 7.5 mg. The patients were followed up for a year. The control examinations were carried out every three months. The therapeutic effect was evaluated from the dynamics of 10 clinical and laboratory parameters. The efficacy of methotrexate treatment provided for a year turned out as follows: significant improvement was attained in 11 patients, improvement was recorded in 9; no changes were demonstrated by 5 patients. Thus, the positive effect was attained in 20 patients (80%). A clinical remission was recorded in 4 patients. Small doses of methotrexate were tolerated well. During one year, the drug was discontinued in none of the patients. Mild side effects were noticed in 11 patients. The temporary drug withdrawal made it possible to continue treating those patients. The majority of the humoral immunity tests showed positive dynamics. As for the titers of rheumatoid factors, such regularity could not be traced. PMID- 1455373 TI - [The possibilities for a modifying influence of basic therapy on the long-term course of rheumatoid arthritis]. AB - Analysis was made of the results of basic therapy carried out for 10-15 years in 71 patients suffering from rheumatoid arthritis (RA) bearing in mind the systematic nature of the treatment. The study included patients with the progressive disease variety and the onset of observation instituted within the first 5 years of RA. It is shown that only basic therapy carried out for many years and practically continuously during the observation period made it possible to control the disease. As a result of such treatment policy, 50% of the patients manifested for a long time (6-10 years) a pronounced decrease or complete suppression of RA activity followed by remission, which was accompanied by retardation and the ceasing of the progression of x-ray alterations and functional insufficiency of the joints. Nonsystematic basic treatment did not exert any material effect on RA. The results of such therapy in patients with the RA standing 10-20 years did not differ from those without the use of the basic drugs. PMID- 1455374 TI - [Pulse therapy with methylprednisolone and cyclophosphamide in systemic juvenile rheumatoid arthritis: the results of an open, parallel, controlled, randomized, 12-month study]. AB - The treatment for systemic JRA is among actual problems of pediatric rheumatology. To evaluate the effectiveness of pulse therapy (PT) with methylprednisolone 25-30 mg/kg/day for 3 consecutive days combined with cyclophosphamide 0.4-0.5 g/sq. m body surface area (BSA) on the 3rd day, repeated quarterly for 12 months, 30 patients with systemic JRA were randomized into 3 groups: 1--those with disease duration (DD) less than 2 years receiving PT (n = 13), 2--with DD 2 years and more (n = 8) receiving PT, and 3--with DD less than 2 years receiving no PT. Children in all 3 groups received concomitant medication (one of nonsteroidal anti-inflammatory drugs, methotrexate 10 mg/sq. m BSA/week and oral steroids). A rapid and significant improvement, according to systemic and articular manifestations as well as laboratory indices occurred in the 1st group, in most of the measured parameters exceeded effects in the other two groups and gave the opportunity to avoid the administration of oral steroids or to give the lesser initial dose. Side effects were minor and completely reversible. PMID- 1455375 TI - [The immunomodulating action of extracorporeal treatment methods and the late effect from their use in patients with rheumatoid arthritis]. AB - Unlike hemocarboperfusion (HCP), plasmapheresis (PA) produces a long-term effect in the treatment of serious cases of rheumatoid arthritis. This explains why the rebound syndrome occurs in PA two times less frequently. The analysis of the immunomodifying action of both the treatments and comparison of their efficacy suggest the conclusion that long-term and complete remissions are associated with the immunosuppressive effects, while the development of exacerbations accompanies the immunomodifying effect. HCP stimulates the immune system, while PA can induce both stimulation and suppression. Therefore, HCP can be used as an adjuvant treatment of highly active rheumatoid arthritis before the basic therapy. In PA immunosuppressive effect, it may be used as an original treatment method. PMID- 1455376 TI - [The preliminary results of using tramal in rheumatoid arthritis patients]. AB - Patients suffering from active rheumatoid arthritis (RA) were examined for the analgesic effect of tramal. All the patients were administered basic therapy and nonsteroidal anti-inflammatory drugs. Tramal produced a beneficial effect in 79% of the patients. The stable analgesic effect ensued on days 3-5 since the onset of continuous treatment. Provided the drug was administered for a short period of time (not more than 14 days), addiction to tramal was not recorded. Only 11% of the patients demonstrated tramal-induced side effects (drowsiness, dizziness, skin itch), seen in cases where the daily dose exceeded 300 mg. PMID- 1455377 TI - [Cartilage-protective preparations in the therapy of osteoarthrosis]. AB - Based on an analysis of the current data on the pathogenesis of osteoarthrosis, the authors provide evidence for the importance of chondroprotective therapy. Present comparative experimental and clinical (tentative) data on the efficacy of chondroprotective drugs. PMID- 1455378 TI - [The clinico-immunological subtypes of systemic lupus erythematosus]. AB - Based on clinico-immunologic studies subtypes of systemic lupus erythematosus (SLE) were distinguished. The ANF-R++H-DNA-CH50 variant determines acute onset of SLE with renal injury in the form of diffuse glomerulonephritis. The ANF-Sp-RNP RF mirrors the development of Raynaud's syndrome, Sjogren's syndrome, polymyositis, pneumosclerosis and myocarditis. The ANF-Sp-Ro-RF variant is associated with skin derangement in the form of discoid foci, anular, papulosquamous eruption, vitiligo, hyperpigmentation, and cerebrovasculitis. The Ro-anti-Po, La-anti-La system is related to the idea of SLE, seronegative in accordance with ANF, when rat liver sections are used as a substrate in immunofluorescence. PMID- 1455379 TI - [Factors that determine the high blood viscosity syndrome in rheumatoid arthritis patients]. AB - High blood viscosity is a syndrome that may be attributed to a group of the most important disorders of microcirculation under different pathological conditions of the body. The given syndrome manifests itself by disorders of red blood cell deformability (RBCD), high plasma and whole blood viscosity. 32 patients with a verified diagnosis of rheumatoid arthritis (RA) were examined, showing varying activity and systemic manifestations. There was a significant decrease of RBCD from 82.0 + 4.5% in patients with grade I activity to 33.0 + 15.0% in patients with grade III activity (p < 0.01). At the same time plasma viscosity remained practically unchanged. Whole blood viscosity rose with RA activity enhancement: in grade I, it was 1.87 + 0.60 relative units, in grade II, it was 2.80 + 0.80 relative units, in grade III, it constituted 5.30 + 3.70 relative units (p < 0.02). It is assumed that RBCD disturbance is one of the most leading signs in the development of high blood viscosity in RA patients. PMID- 1455380 TI - [The bioenergetic x-ray absorptiometry of the spine in rheumatoid arthritis patients with aseptic femur head necrosis]. PMID- 1455381 TI - [The use of taktivin for modulating the functional activity of the neutrophilic granulocytes in patients with systemic lupus erythematosus]. AB - The dynamics of the synthesis of active oxygen forms by neutrophilic granulocytes was studied and compared in patients with systemic lupus erythematosus (SLE) given conventional therapy (n = 14) and combined therapy with the use of tactivin (n = 17). Evaluation of spontaneous fluorescence of neutrophils (FN) and of that induced by suspension of the killed Staphylococcus culture revealed an increase of the latter one after tactivin treatment, which was accompanied by the regression of articular and cutaneous syndromes and trophic disorders. It has been discovered that the dynamics of FN in the treatment with the use of tactivin was dependent on the initial characteristics of the synthesis of active oxygen forms. PMID- 1455382 TI - [The serum neopterin level in acute rheumatic fever]. AB - Acute rheumatic fever (ARF) is a systemic inflammatory disease etiologically related to infection with group A streptococcus characterized by a broad spectrum of disorders of cellular and humoral immunity. To estimate the activity of the immunopathological process and to forecast myocardial derangement in ARF patients, measurements were made of neopterin in the serum of ARF patients. Nine men with ARF serving in the armed forces were examined. The control group comprised 24 donors. The reference group included 13 patients with dilated cardiomyopathy and 14 with chronic myocarditis. The mean level of neopterin in ARF patients was equal to 14.5 +/- 12.2 nM/l and was significantly higher than in the donors (5.0 +/- 2.0 nM/l). In patients with dilated cardiomyopathy and chronic myocarditis, it was 9 +/- 6 and 16 +/- 11 nM/l, respectively. On more careful clinical analysis the highest level of neopterin was recorded in 3 patients with impairment of the valvular apparatus of the heart. That level was observable during the whole period of the follow-up of the patients. In other patients, no impairment of the valves was detected, whereas the concentration of neopterin fell to normal. Therefore, the rise of the level of neopterin was described for the first time in patients with ARF. Besides, a relationship was found between the high level of neopterin and impairment of the valvular apparatus of the heart. PMID- 1455383 TI - [The heterogeneity of systemic lupus erythematosus due to the antiphospholipid syndrome]. PMID- 1455384 TI - [Amyloidosis and antibodies to heat-shock proteins]. PMID- 1455385 TI - [The importance of an early stress test in patients with myocardial infarct and heart failure in the acute period of the disease]. AB - The mechanisms of acute myocardial infarction depend on the site of myocardial infarction (MI). In anterior MI, the main factor is a large area of injury; in inferior MI, of importance is dysfunction of the papillary muscles and multiple lesions of the coronary artery in addition to the above factor. The site, the area of injury and the status of the coronary bed influence the rate, character and prognostic value of early load test criteria and contractile function of the left ventricle. In anterior MI, elevation of the ST segment is the most frequent criterion; in inferior MI, its depression. Their combination with other criteria for test discontinuation point to multiple lesions of the coronary artery. In patients with anterior MI, the ejection fraction of the left ventricle amounting to 40%, inadequate growth of AP, anginous pain and the T dominant elevation of the ST segment are unfavourable predictors, allowing the patients to be differentiated in accordance with the risk of postinfarction complications. PMID- 1455386 TI - [Experience with the practical training of students in a department of internal diseases]. PMID- 1455387 TI - [The results of a retrospective examination of patients with acute rheumatic fever]. AB - The authors describe the results obtained during retrospective examinations of 45 subjects who suffered from acute rheumatic fever 10-14 years before. Of these, 19 subjects were treated with prednisolone in the acute disease period, 16 with indomethacin, and 8 subjects with voltaren. The examinations were mostly randomized (30 subjects); no differences in the anti-inflammatory effect were discovered. Heart disease was found in 9 persons (20%). Of these, 6 were treated with prednisolone, 2 with indomethacin, and 1 with voltaren. The disease relapses were recorded in 4 of them, the signs of valvulitis in the past were shown only by 2 persons (echocardiographically). 12 persons (27%) had mitral valve prolapse which had not been diagnosed on the first admission to the hospital, with any clinical signs of hypermotility lacking. In 18 persons (40%) having no valve lesions (disease, prolapse), an x-ray examination revealed a slight increase of the heart size, estimated as a manifestation of postmyocardial cardiosclerosis. Thus, it has been shown that modern anti-inflammatory therapy does not prevent the development of heart disease. Apparently, its onset is related to specific proneness in some of the patients. PMID- 1455388 TI - [The results of a clinico-serological examination of 60 patients with Lyme disease]. AB - Clinical and serological examinations were carried out in 60 patients with Lyme disease. The diagnosis was established on the basis of the disease marker--tick borne migrating erythema and serological data obtained with the use of indirect immunofluorescence and Western blot. The spectrum of clinical manifestations and the rate of different clinical syndromes are described and compared with the data by this country and foreign authors. It is shown that Borrelia infection is capable of imitating rheumatic diseases. PMID- 1455389 TI - [2 cases of trichinelliasis]. PMID- 1455390 TI - OSHA without tears. Part two: Developing an exposure control plan. PMID- 1455391 TI - Baby bottle tooth decay prevention--a new program for the Texas Department of Health. PMID- 1455392 TI - A specific immunologic assay for functional plasminogen activator inhibitor 1 in plasma--standardized measurements of the inhibitor and related parameters in patients with venous thromboembolic disease. AB - A new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-1 complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects. PMID- 1455393 TI - Prolonged bleeding time in patients with lupus anticoagulant. AB - Platelet adhesion to collagen under flow conditions was studied in 18 patients with lupus anticoagulant, seven of which showed a prolonged bleeding time in the presence of a normal platelet count. The effect of patient plasma, IgG and purified anticardiolipin antibodies on platelet adhesion was also examined. We found a significant reduction of platelet adhesion in patients with lupus anticoagulant, which was more evident in patients with prolonged bleeding time. This platelet adhesion defect could be attributed to a plasma factor. In fact, patients' platelets regained normal adhesion when mixed with normal plasma, whereas controls' platelets showed abnormal adhesion in the presence of patient plasma. A causative role of antiphospholipid antibodies was demonstrated in experiments using purified immunoglobulins and anticardiolipin antibodies. PMID- 1455394 TI - Comparative arterial antithrombotic activity of clopidogrel and acetyl salicylic acid in the pig. AB - We investigated the comparative antithrombotic properties of clopidogrel, an analogue of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs. On each animal, clopidogrel or aspirin were used to treat the thrombotic process on the left femoral artery and to prevent this process on the right femoral artery. Sequentially: an injury and stenosis were carried out on the left femoral artery; the thrombotic process was monitored with a Doppler during a 30-min observation period for cyclic flow reductions or permanent cessation of flow; after the first cyclic flow reduction occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine (0.4 micrograms kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation of flow; then injury and stenosis were applied on the right femoral artery. Before and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions were efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened (> 15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal and epinephrine restored it in a second animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455395 TI - Plasminogen levels in healthy volunteers--influence of age, sex, smoking and oral contraceptives. AB - There is considerable doubt as to the importance of reduced plasminogen (PLG) activity as a risk factor for venous thrombosis. In the present study we have identified a wide range of PLG activities (25-200%) in a cohort of 9,611 blood donors. Males and females not taking hormonal contraceptives show a similar distribution of PLG, however, variation related to age appears to follow a different pattern in males and females. These differences are of doubtful clinical importance as are differences related to smoking. In contrast, females taking hormonal contraceptives or hormone replacement therapy (HRT) have up to 25% higher mean PLG levels in younger females but a less marked elevation (10%) is seen in 40-50 year olds. A PLG activity < 65% was recorded in 61 donors, none of whom appeared to have a history of thrombosis. These findings do not support the notion that reduced PLG is an important thrombophilic risk factor, however, further investigation of the donors with low PLG is required. PMID- 1455396 TI - A novel rat model of thrombogenicity: its use in evaluation of prothrombin complex concentrates and high purity factor IX concentrates. AB - A non-stasis rodent model of thrombogenicity has been used for dose-ranging studies with a conventional prothrombin complex concentrate (PCC) and to evaluate high purity factor IX concentrates from different manufacturers. Fibrin monomer (soluble fibrin) and fibrinopeptide A (FPA) were monitored before and after infusion of test solution. FPA was found to be the more sensitive and reproducible indicator of thrombogenicity and exhibited a dose-related elevation after infusion of the PCC at doses of between 100-300 IU/kg. In contrast the amounts of FPA generated after 300 IU/kg of the high purity factor IX products were similar to control infusions of albumin. PMID- 1455399 TI - Structure, kinetics, and function of human and rhesus plasma prekallikreins are similar. AB - To determine if rhesus monkeys (Macaca mulatta) could serve as a model for studying the role of the contact system in the pathophysiology of human infections, we compared structural, kinetic, and functional characteristics of plasma prekallikrein and its activation products in rhesus and humans. Three prekallikrein variants (85-, 89- and 93-kDa) were revealed in rhesus plasma as compared with the two variants (85- and 88-kDa) in human plasma by immunoblotting with the monoclonal antibody MAb 13G11. The prekallikrein concentration in rhesus plasma was 1.5-fold that in human plasma as determined by computerized immunoblot analyses (CIBA) and amidolytic activity. The electrophoretic mobility of prekallikrein from plasma of both species increased after deglycosylation. Inhibition of prekallikrein activation by MAb 13G11 was 55% (rhesus plasma) and 76% (human plasma), with similar inhibition curves. Immunoblots of activated rhesus plasma showed prekallikrein, complexes of kallikrein with C1 inhibitor, alpha 2-macroglobulin and approximately 60-kDa inhibitor(s) (viz. antithrombin III), and 45-kDa fragments, like those in activated human plasma. Concentrations and molecular masses of factor XII and high molecular weight kininogen were similar in rhesus and human plasma. The activated partial thromboplastin time (APTT) and prothrombin time were 20.1 +/- 1.6 and 9.7 +/- 0.3 s for rhesus and 32.0 +/- 5.6 and 12 +/- 0.5 s for human plasma. Human and rhesus APTTs were similar when prekallikrein concentrations in human and rhesus plasma became alike by adding human purified prekallikrein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455397 TI - Fibrinolytic potential and antiphospholipid antibodies in systemic lupus erythematosus and other connective tissue disorders. AB - We studied the fibrinolytic response before and after venous occlusion (VO) in 30 patients with systemic lupus erythematosus (SLE), 25 with rheumatoid arthritis (RA) and 25 with different connective tissue disorders. Results were compared in patients with and without antiphospholipid antibodies (APA) and a history of either thrombosis or abortions. Before occlusion plasma levels of tissue-type plasminogen activator (t-PA) antigen and its inhibitor (PAI-1) were significantly higher in the patient group (p < 0.001). After occlusion, a low fibrinolytic activity on fibrin plates (p < 0.005) was observed in the same group. t-PA capacity and t-PA release were similar in relation to controls. The plasma PAI-1 activity was significantly elevated in each group of patients (p < 0.005) as compared to the control group. No significant differences with respect to t-PA and PAI-1 were observed in patients as to the presence or absence of thrombosis. There was also no correlation between the fibrinolytic changes and the presence of APA. It is concluded that an impairment of the fibrinolytic system, mainly related to increased PAI-1 levels, is present in most patients with connective tissue disorders, although these changes did not correlate with the presence of APA or the incidence of thrombosis. PMID- 1455398 TI - Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats. AB - Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K1 resulted in the normalization of these coagulation factors. After taking liver biopsies it was demonstrated that the coagulation abnormality was accompanied by a defective gamma-glutamyl-carboxylase, which had a decreased affinity for both vitamin K hydroquinone and propeptide. This observation prompted us to study in a well-defined in vitro system the possible allosteric interaction between the propeptide binding site and the vitamin K hydroquinone binding site on carboxylase. It was shown that by the binding of a propeptide containing substrate to gamma-glutamylcarboxylase the apparent KM for vitamin K hydroquinone is decreased about 20-fold. On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully explained. PMID- 1455400 TI - Heterozygous abnormal fibrinogen Osaka III with the replacement of gamma arginine 275 by histidine has an apparently higher molecular weight gamma-chain variant. AB - Congenitally abnormal fibrinogen Osaka III with the replacement of gamma Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and the polymerization of preformed fibrin monomer which was prepared by the treatment of fibrinogen with thrombin or reptilase was also markedly defective. Propositus' fibrinogen had normal crosslinking abilities of alpha- and gamma chains. Analysis of fibrinogen chains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the system of Laemmli only revealed the presence of abnormal gamma-chain with an apparently higher molecular weight, the presence of which was more clearly detected with SDS-PAGE of fibrin monomer obtained by thrombin treatment. Purified fragment D1 of fibrinogen Osaka III also seemed to contain an apparently higher molecular weight fragment D1 gamma remnant on Laemmli gels, which was digested faster than the normal control by plasmin in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA). PMID- 1455401 TI - The influence of glycosylation on the catalytic and fibrinolytic properties of pro-urokinase. AB - We previously found that human pro-UK expressed in Escherichia coli is more active in fibrinolysis than recombinant human pro-UK obtained from mammalian cell culture media. To determine whether this difference is related to the lack of glycosylation of the E. coli product, we compared the activity of E. coli-derived pro-UK [(-)pro-UK] with that of a glycosylated pro-UK [(+)pro-UK] and of a mutant of pro-UK missing the glycosylation site at Asn-302 [(-)(302)pro-UK]. The latter two pro-UKs were obtained by expression of the human gene in a mammalian cell. The nonglycosylated pro-UKs were activated by plasmin more efficiently (approximately 2-fold) and were more active in clot lysis (1.5-fold) than the (+)pro-UK. Similarly, the nonglycosylated two-chain derivatives (UKs) were more active against plasminogen and were more rapidly inactivated by plasma inhibitors than the (+)UK. These findings indicate that glycosylation at Asn-302 influences the activity of pro-UK/UK and could be the major factor responsible for the enhanced activity of E. coli-derived pro-UK. PMID- 1455402 TI - Adrenergic stimulation of regional plasminogen activator release in rabbits. AB - The purpose of this study was to determine whether different regions of the rabbit vascular system show variations in the rate of plasminogen activator (PA) secretion. To start, we evaluated the time course, dose response and adrenergic specificity of PA release. Infusion of 1 microgram/kg of epinephrine stimulated a 116 +/- 60% (SD) increase in PA activity that peaked 30 to 60 s after epinephrine administration. Infusion of 1 microgram/kg of norepinephrine, isoproterenol and phenylephrine had no effect on PA activity. Pretreatment with phentolamine, an alpha adrenergic antagonist, blocked the release of PA by epinephrine while pretreatment with the beta blocker propranolol had no effect. This suggests that PA release in the rabbit was mediated by some form of alpha receptor. Significant arterio-venous differences in basal PA activity were found across the pulmonary and splanchnic vascular beds but not the lower extremity/pelvic bed. After stimulation with epinephrine, PA activity increased 46% across the splanchnic bed while no change was seen across the lower extremity/pelvic bed. We conclude that several vascular beds contribute to circulating PA activity in the rabbit, and that these beds secrete PA at different rates under both basal and stimulated conditions. PMID- 1455403 TI - Antithrombotic properties of dermatan sulphate (MF 701) in haemodialysis for chronic renal failure. AB - The therapeutic potential of the glycosaminoglycan (GAG), dermatan sulphate (DS), as an antithrombotic agent in humans has yet to be established. We have performed dose ranging studies of DS to determine its effectiveness as an antithrombotic agent in patients (n = 6-8) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients dialysing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg/kg DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efficacy of an i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg kg-1 h-1 and a DS bolus of 5 mg/kg plus an infusion of 1 mg kg-1 h-1 over 5 h, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. Plasma levels of fibrinopeptide A (FPA) and thrombin-antithrombin (TAT) were used as markers of fibrin formation and thrombin generation during dialysis using both membranes. The changes in DS concentration following administration of the different doses were similar in Studies 1 and 2. However, the effectiveness of DS as an anticoagulant appeared to depend markedly on the different dialyser types used in the two studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455404 TI - Decreased platelet membrane fluidity due to glycation or acetylation of membrane proteins. AB - Platelets from diabetic subjects and animals are hypersensitive to agonists in vitro. Membrane fluidity modulates cell function and previously we observed reduced membrane fluidity in platelets from diabetic patients associated with hypersensitivity to thrombin. We previously reported that decreased fluidity of isolated platelet membranes from diabetic patients is associated with increased glycation of platelet membrane proteins, but not with any change in the cholesterol to phospholipid molar ratio. We have now examined in vitro whether incubation of platelet membranes in a high glucose medium causes sufficient glycation to reduce membrane fluidity. Incubation of platelet membranes from control subjects in a high glucose (16.1 mM) medium for 10 days at 37 degrees C led to an increase in the extent of glycation of membrane proteins and a decrease in membrane fluidity (indicated by an increase in steady state fluorescence polarization); most of the changes occurred within the first 3 days of incubation. Incubation of platelet membranes with 5.4 mM glucose had less effect. In contrast, incubation of platelet membranes with the same concentrations of 1-0 methylglucose did not cause a change in either the extent of glycation of proteins or membrane fluidity. We also determined if acetylation by aspirin or acetyl chloride of the sites available for glycation on platelet membrane proteins leads to a similar reduction in membrane fluidity. Pretreatment of platelet membranes with aspirin or acetyl chloride diminished the extent of glycation that occurred when platelet membranes were subsequently incubated with glucose, but membrane fluidity was reduced even in the absence of glucose; subsequent incubation with glucose caused no further reduction in membrane fluidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455405 TI - Cigarette smoking increases thromboxane A2 formation without affecting platelet survival in young healthy females. AB - Smoking is a risk factor for the development of atherosclerotic cardiovascular disease, in men as well as in women. An increased urinary excretion of the thromboxane metabolite 2,3-dinorthromboxane B2 (Tx-M) has been observed in smokers of both genders, suggesting that cigarette smoking may facilitate cardiovascular disease via an action on the platelets. The present study addressed the hypothesis that the increased Tx-M excretion in female smokers reflects a true facilitation of platelet reactivity in vivo, rather than an increased destruction of the platelets. In healthy female volunteers (aged 20-46 years, 18 smokers and 17 non-smokers) platelet life-span and indices of platelet activity were determined, together with plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, peripheral blood cell counts and hematocrit. The urinary excretion of Tx-M was higher in smokers than in non-smokers (361 vs. 204 pg/mg creatinine, respectively, p < 0.05), while plasma and urinary beta thromboglobulin, plasma platelet factor 4, platelet mean life-span and platelet production rate did not differ between the groups. PAI-1 activity, white blood cell count and hematocrit were higher in smokers than in non-smokers (p < 0.05). These data indicate that smoking facilitates platelet formation of thromboxane A2 without affecting platelet survival; i.e. it increases the activity of platelets without affecting their viability to a measurable extent. Such an increase in platelet activity, operating in parallel to a reduced fibrinolytic activity and a higher hematocrit and white blood cell count, may play an etiological role in smoking-induced cardiovascular disease in women. PMID- 1455406 TI - Human platelets exposed to mechanical stresses express a potent lipoxygenase product. AB - Human platelets exposed to hypotonicity undergo regulatory volume decrease (RVD), controlled by a potent, yet labile, lipoxygenase product (LP). LP is synthesized and excreted during RVD affecting selectively K+ permeability. LP is assayed by its capacity to reconstitute RVD when lipoxygenase is blocked. Centrifugation for preparing washed platelets (1,550 x g, 10 min) is sufficient to express LP activity, with declining potency in repeated centrifugations, indicating that it is not readily replenishable. When platelet suspension flows in a vinyl tubing (1 mm i.d.), at physiological velocity, controlled at 90-254 cm/s, LP formation increases as a function of velocity but declines as result of increasing the tubing length. Stirring the platelets in an aggregometer cuvette for 30 s, yields no LP unless the stirring is intermittent. No associated platelet lysis or aggregation are observed following the mechanical stress applications. These results demonstrate that although mechanical stresses result in LP production, the mode of its application plays a major role. These results may indicate that LP is synthesized under pathological conditions and could be of relevance to platelets behavior related to arterial stenosis. PMID- 1455407 TI - Stored platelets release nucleotides as inhibitors of platelet function. AB - It is well known that the function of platelets decreases progressively during storage of platelet concentrates at room temperature. To investigate this phenomenon in more detail, we have resuspended platelets that had been stored for 24 h or 72 h in fresh plasma, and we have measured the aggregation response and the ATP secretion. Conversely, the effect of plasma in which platelet concentrates (PC) had been stored for 24 h or 72 h, was tested on fresh platelets. Both the aggregation response to collagen and ADP and the collagen induced ATP secretion of stored platelets partially recovered after incubation with fresh plasma (p < 0.05). The same parameters measured with fresh platelets incubated in stored PC-plasma were found to be significantly reduced in comparison with the response of fresh platelets in fresh plasma (p < 0.05). Finally, platelets were stored in a plasma-free medium, suitable for platelet storage and the supernatant was tested. This supernatant inhibited the function of fresh platelets in a storage time-dependent fashion. Boiling of these supernatants did not change the inhibiting capacities, whereas filtration over active charcoal did. Analysis of this supernatant revealed AMP and diadenosine tetraphosphate, which both inhibit platelet function. These data show that stored platelets release nucleotides that inhibit platelet function in a reversible manner. This phenomenon may contribute to the decrease of platelet function during storage and the recovery of platelet function after transfusion. PMID- 1455408 TI - Classification of Glanzmann's thrombasthenia based on the intracellular transport pathway of GPIIb-IIIa. PMID- 1455409 TI - A new case of combined deficiency of vitamin K dependent coagulation factors. PMID- 1455410 TI - Inherited defect of blood clotting factor VIII (haemophilia A) in sheep. PMID- 1455411 TI - DDAVP infusion does not affect plasma levels of endothelin-1 in four normal subjects. PMID- 1455412 TI - Usefulness of determination of factor VIII intron 7 polymorphism by a non radioactive technique for carrier detection of hemophilia A. PMID- 1455413 TI - No increase of beta 2-glycoprotein I levels in patients with antiphospholipid antibodies. PMID- 1455414 TI - A partial role of serotonin in normalization of the bleeding time by DDAVP in uraemic rats. PMID- 1455415 TI - Computer-assisted three-dimensional volumetry of the human pulmonary acini. AB - Computer-aided three-dimensional (3-D) volumetry of human pulmonary acini was undertaken using the left upper lobe of a 51-year-old female operated for small lung cancer. A normal part of this lobe, fixed by intrabronchial infusion with a mixture of polyethylene glycol and formalin, was subjected to serial sectioning, using a special slicer, into 48 serial slices of 0.5 mm in thickness. A soft x ray radiograph was prepared from each slice at x 12, and the contours of airways and acinar boundaries contained in it were input by digitization into a microcomputer for 3-D reconstruction and volumetry. The estimated volumes of 130 acini were unexpectedly uniform, showing a normal type distribution with a mean of 172.7 +/- 37.9 mm3. No significant correlation proved to exist between the volume of acini and the number of branching generation of the terminal bronchioles (TBs) they received. Furthermore, there was no significant difference in volume among the acini facing the costal surface, those facing the mediastinal surface and those not facing any pleural surface. However, the generation number of TBs was shown to differ significantly with the location of acini. These results suggest that the tree of conductive airways is designed so as to meet the requirement of constant acinar volume. PMID- 1455416 TI - Prevalence of HTLV-I antibody in pulmonary cryptococcosis. AB - A retrospective study was done to determine the prevalence of anti-HTLV-I antibodies in patients with pulmonary cryptococcosis. None of the 19 patients with pulmonary cryptococcosis had underlying immunodeficiency. Anti-HTLV-I antibody was present in 6 (32%) of 19 patients with pulmonary cryptococcosis, a significantly higher prevalence than found in patients with bronchial asthma (4 (7%) of 58) (p less than 0.01, chi-square test). No statistical difference was noted when anti-HTLV-I antibody seropositivity was compared to that of patients with pulmonary tuberculosis (16% (17/105)), lung cancer (17% (22/129)) and pneumonia (9% (6/64)). A reduced cellular immunity as shown by lymphopenia, the CD4/CD8 ratio, and purified protein derivative skin test was found in only 1 (5%) of 19, 2 (12%) of 17, and 6 (33%) of 18 patients, respectively. These results do not explain the susceptibility to pulmonary cryptococcosis in HTLV-I carriers. This is the first report of high prevalence of pulmonary cryptococcosis in HTLV-I carriers and it raises the question whether HTLV-I carriers are more susceptible to opportunistic infections and other malignancies probably due to subtle immunological abnormalities. PMID- 1455417 TI - The effects of intrarenal infusion of recombinant human erythropoietin on mean arterial pressure and renal hemodynamics in anesthetized rabbits. AB - The effects of recombinant human erythropoietin (rHuEPO) on mean arterial pressure (MAP) and renal hemodynamics were studied in anesthetized rabbits without renal failure. Intrarenal infusion of rHuEPO at a rate of 100 U/min for 30 min resulted in no change in MAP, renal blood flow, or renal vascular resistance. rHuEPO also produced no significant change in glomerular filtration rate filtration fraction, or arterial hematocrit. These results demonstrate that rHuEPO has no direct effects on MAP or renal hemodynamics in anesthetized rabbits without renal failure. PMID- 1455418 TI - Histopathological evaluation on the effect of induced hypertension chemotherapy presurgically performed in patients with advanced carcinoma of the stomach. AB - Stomachs resected from 13 patients with an advanced gastric carcinoma were examined histopathologically to evaluate the effect of induced hypertension chemotherapy (IHC) using angiotensin II. Eight of the 13 patients, randomly chosen, were treated presurgically by IHC with a regimen of 5-fluorouracil, adriamycin and mitomycin C; the same regimen was used in the remaining five patients but without inducing hypertension. Clinical evaluation of the effect gave rise to the confirmation, presurgically, of complete response in three and partial response (PR) in two patients in the IHC group, whereas in the non-IHC group, the highest rating was PR, which was attained in only one patient. Also in the histopathological assessment based on a five-step grading, the IHC group earned in average a higher score than the non-IHC group, with a difference proved significant by Wilcoxon's test. A histological rating of Grade 3, the highest effectiveness, was given to three patients in the IHC group, in one of whom the resected stomach disclosed no viable carcinoma cells but only fibrotic areas replacing carcinoma. There was also a correlation between the clinical and histological ratings as proved to be significant by Spearman's test. We conclude that in gastric carcinoma, the effect of chemotherapy is enhanced by angiotensin II-IHC. PMID- 1455419 TI - Tetralogy of Fallot with anomalous origin of left pulmonary artery. AB - Between 1971 and 1990, 7 patients of tetralogy of Fallot with anomalous origin of left pulmonary artery underwent intracardiac repairs at Tohoku University Hospital. They were 2 males and 5 females with ages ranging from 4 to 26 years old. The right pulmonary artery connected to right ventricle in all cases, whereas no communications between right ventricle and the left pulmonary artery were found. The left pulmonary artery directly originated from the ascending aorta in 2 patients (group I) and connected to the ductus arteriosus in 5 patients (group II and III). In 2 patients (group II), the left pulmonary artery was separated from the pulmonary arterial trunk by the intraluminal membrane, receiving blood supply through the ductus. In the remaining 3 patients (group III), there were no continuations between both pulmonary arteries. At the correction, communication between the left pulmonary artery and the pulmonary arterial trunk could be reconstructed in groups I and II. However, it was not possible in group III, because the ductus arteriosus and the left pulmonary artery had already been occluded before the intracardiac repair. In group III, ventricular septal defect was closed using a one-way valved patch or a perforated patch to decrease supersystemic right ventricular pressure. Postoperative right ventricular aortic pressure ratio was between 0.5 and 0.8 in groups I and II, and between 0.8 and 1.0 in group III. Three patients (one in each group) died after the operation. Severe pulmonary vascular obstructive disease was found in the left lung of group I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455420 TI - Radioresponse and prognosis of malignant glioma. AB - Radioresponse and prognosis of 91 malignant gliomas were studied to examine the efficacy of radiotherapy. There was no case of complete response. No statistically significant difference was observed among the prognoses of patients with various radiation methods. General survival rate was significantly higher than relapse-free survival rate both in astrocytoma grade III and in glioblastoma. This means that the retreatment after relapse is exceedingly important in any malignant glioma. In comparison with reported resection alone data, the efficiency of radiotherapy was evident in astrocytoma grade III and a part of glioblastoma; cases with minimal or no contrast enhanced area (CEA) in CT scans prior to irradiation. Poor radioresponders of glioblastoma with CEA should be reoperated. PMID- 1455421 TI - Effect of chronic consumption of methylparathion on rat brain regional acetylcholinesterase activity and on levels of biogenic amines. AB - Wistar rat pups (female) were exposed to methylparathion (MPTH) by gastric intubation in single doses, or in a chronic regimen of different durations. A single dose of 1 mg MPTH/kg body weight in 15-day-old pups caused a significant decrease of acetylcholinesterase (AChE) activity in cerebellum (CE), motor cortex (MC) and brain stem (BS). The effect began to appear in about 20 min after administration, the peak effect was attained in 120 min and later on this waned off completely by 24 h. The effect was similar in young (15 days) and in adult (70 days) rats. A single dose of 0.2 mg MPTH/kg in 15 day old pups caused a reduction of AChE activity only in the BS, while a 0.1 mg MPTH/kg single dose given to 15-day-old pups caused no effect even in seven regions of the brain examined. Effect of low dose chronic administration of MPTH on AChE activity was also studied in CE, MC, BS, hippocampus (HI), striatum-accumbens (SA), spinal cord (SC) and also in the hypothalamus (HY). Administration of 0.1 mg MPTH/kg from second day to 15 days of age caused significant reduction of AChE activity in only 2 of the 7 brain regions studied. Administration of double the dose (0.2 mg MPTH/kg) and for a longer duration (2nd day to 150 days of age), caused a depression in all the brain regions studied. In all these regions, the levels of NA, DA and 5HT did practically not change. The results suggest that chronic consumption of MPTH leads to a moderate decrease of AChE activity in several brain regions. PMID- 1455422 TI - Absence of interactions on hepatic retention and 7-ethoxyresorufin-O-deethylation activity after co-administration of 1,2,3,7,8-pentachlorodibenzo-p-dioxin and 2,4,5,2',4',5'-hexachlorobiphenyl. AB - Interactions between 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PnCDD) and 2,4,5,2',4',5'-hexachlorobiphenyl (HxCB) on hepatic retention of PnCDD and on cytochrome P450 related enzyme activities were studied in male C57BL/6J mice. Animals received 8 nmol PnCDD/kg orally, alone or in combination with 1-416 mumol HxCB/kg. Co-administration of HxCB did not alter the hepatic retention of PnCDD or the 7-ethoxyresorufin-O-deethylation (EROD) activity induced by PnCDD as observed after 1 week. A small antagonistic effect on total cytochrome P450 content and 7-pentoxyresorufin-O-depentylation (PROD) activity was observed at a dose of 8 nmol PnCDD/kg and 1 mumol HxCB/kg. Furthermore, a significant induction of PROD activity by PnCDD was found. This was not expected, since PROD activity is considered to be a specific marker for CYP2b related enzyme activity and this type of cytochrome P450 is not induced by polychlorinated dibenzo-p-dioxins such as PnCDD. It is concluded that, under these short-term experimental conditions, no toxicokinetic basis was found to explain the antagonistic effects on hepatic cytochrome P450 related activities observed in the present study or in other studies. PMID- 1455423 TI - Effects of 2,5-hexanedione on the ovary and fertility. An experimental study in mice. AB - Sixty-day-old virgin female Swiss CD1 mice were treated with 1.5% 2,5-hexanedione in their drinking water; control mice received tap water; duration of treatment was either 4 or 6 weeks. Under these conditions the treated mice did not show any clinical symptoms although electromyography revealed some signs of polyneuropathy. Protein and DNA content per mg of ovarian tissue in treated mice were not significantly different from controls. Histological examination of ovarian sections at the light microscope level showed no significant alterations after exposure. A morphometric study revealed a statistically significant reduction in the number of growing oocytes after 6 weeks of treatment. For fertility studies three groups of 15 female mice each were treated for 0, 4 or 6 weeks as above and then permanently housed with untreated proven breeder male mice (one male per female); cages were checked daily for newly born mice. All litters appeared normal by gross examination. During the first 14 weeks of continuous mating the mean litter size (number of newborns per litter) remained about 11.4 in all groups; this number subsequently began to decrease. Control and 4-week treatment regression curves did not differ statistically, while the slope of the 6-week line was significantly steeper, indicating a faster decrease in litter size over time and a shortening of fertile life in the latter group of treated females. PMID- 1455425 TI - Liver delta-aminolevulinate dehydratase activity in amitriptyline- or chlorpromazine-treated rats. AB - Amitriptyline (AMT) and chlorpromazine (CPZ) (0.5 mg per animal, i.p.) were injected into rats separately for 30 days and their effects on heme metabolism in liver were examined. Significant decreases in the delta-aminolevulinate dehydratase activity were observed following the administration of both drugs (mean value of AMT-group: 6.58 U/g tissue; and CPZ-group: 7.04 U/g tissue) in comparison to that of controls (11.71 U/g tissue); however total liver heme content was not altered. When 24-h urinary excretions of delta-aminolevulinate (ALA) and porphobilinogen (PBG) were measured on the last day of the experiment, a slight (AMT-group: 38.40 micrograms/day) to distinct (CPZ-group: 59.11 micrograms/day) increase of urinary ALA was observed, while PBG excretion tended to decline only moderately under CPZ (3.52 micrograms/day), but significantly in presence of AMT (2.16 micrograms/day). Mean values obtained from control group were 32.12 micrograms/day for ALA and 4.25 micrograms/day for PBG. PMID- 1455424 TI - Cadmium-induced hepatic endothelial cell injury in inbred strains of mice. AB - Susceptibility to cadmium (Cd) hepatotoxicity differs among inbred strains of mice. For example, C3H/HeJ mice are sensitive to Cd-induced hepatotoxicity, whereas DBA/2J mice are resistant. The mechanism of genetic predisposition to Cd hepatotoxicity is unknown. A contemporary theory for acute target organ intoxication maintains that Cd initially damages vascular endothelium and parenchymal cell injury is a secondary event that results from localized ischemia. In the present study, the hypothesis that hepatic endothelial cells (EC) of C3H mice are more susceptible to Cd toxicity than those of DBA mice was tested. Hepatic parenchymal and endothelial cells were grown separately on monolayer cultures for 22 h and subsequently treated with various concentrations of Cd. Hepatocellular toxicity was assessed by lactate dehydrogenase leakage and intracellular K+ loss, whereas endothelial cell injury was assessed by trypan blue exclusion and the inhibition of protein synthesis. The susceptibility of hepatocytes to the cytotoxic effects of Cd was identical between strains. In contrast, the vulnerability of EC to Cd intoxication was strain-dependent. When exposed to 2.5-10.0 microM Cd, EC of Cd-sensitive mice were more susceptible to the cytotoxic effects of Cd than those of Cd-resistant mice. Basal metallothionein (MT) levels as well as Cd uptake into EC were similar in the two strains. Following Cd exposure, EC of Cd-sensitive mice accumulated similar amounts of MT as EC of Cd-resistant mice. These observations suggest that the microvasculature in livers of inbred mice is the target tissue responsible for strain-dependent susceptibility to Cd-induced liver injury. The mechanisms that account for this genetic variation in endothelial cell response to Cd are unknown, but do not appear to be related to the cellular disposition of Cd nor to a defect in the metabolism of MT. PMID- 1455426 TI - The relative effects of hypoxic hypoxia and carbon monoxide on brain function in rabbits. AB - New Zealand white rabbits were exposed to control conditions (n = 11), or to either a progressive hypoxic hypoxia produced by dilution of oxygen (O2) with nitrogen (n = 10) or a 1% carbon monoxide (CO) admixture for 15 min (n = 11). Both exposures caused a significant increase in cerebral blood flow (CBF) of up to 300% such that O2 delivery to the brain was unchanged. In the hypoxia group, a cortical somatosensory evoked response (CSER) was unaffected until the arterial O2 tension was below 20 mmHg. At this time, the rabbits became hypotensive, O2 delivery to the brain decreased dramatically and the CSER could not be elicited. In contrast, despite the maintenance of O2 delivery to the brain during and after the CO exposure, the CSER voltages were halved during the exposure and only recovered to about 80% of baseline subsequently. We conclude that the primary toxicity of CO to the brain in rabbits is not due to a reduction in O2 delivery. PMID- 1455428 TI - Effect of endosulfan (thiodan) on vitellogenesis and its modulation by different hormones in the vitellogenic catfish Clarias batrachus. AB - This programme was planned in order to study the reproductive dysfunction caused by endosulfan in the fish Clarias batrachus with special reference to vitellogenesis. Vitellogenin was measured by radioimmunoassay. Endosulfan caused a drastic reduction in the plasma vitellogenin which was partially reversed by estradiol-17 beta (E2) in intact and ovariectomized fish. Hormones in combination were more effective than any single hormone in overcoming the impact of endosulfan. Triiodothyronine (T3), ovine luteinizing hormone releasing hormone (oLHRH) were effective in minimizing the effect of endosulfan whereas cortisol (F) and ovine somatotropic hormone (oStH) did not reduce the effect of endosulfan. Amongst the combined hormone treatments, E2 + oLHRH and E2 + T3 were the most potent in overcoming the effect of endosulfan on vitellogenesis. PMID- 1455427 TI - Endrin-induced urinary excretion of formaldehyde, acetaldehyde, malondialdehyde and acetone in rats. AB - Previous studies have shown that endrin induces an oxidative stress in rats as demonstrated by an increase in hepatic lipid peroxidation, a decrease in glutathione content and a decrease in the activity in selenium-dependent glutathione peroxidase. We have therefore examined the effects of orally administering 1.5, 3.0, 4.5 and 6.0 mg endrin/kg on the urinary excretion of the lipid metabolites formaldehyde, malondialdehyde, acetaldehyde and acetone. The simultaneous determination of these four lipid metabolites may be a useful biomarker for assessing exposure to xenobiotics which induce an oxidative stress and enhanced lipid peroxidation. Urine samples were collected up to 72 h post treatment. The identities of the lipid metabolites were confirmed by gas chromatography-mass spectroscopy, while the 2,4-dinitrophenylhydrazine derivatives of these metabolic products were quantitated by high pressure liquid chromatography. Maximum increases in the excretion of the four lipid metabolites occurred at approx. 24 h post-treatment at all doses with no significant increases in excretion occurring thereafter. The maximum increases in excretion of malondialdehyde, formaldehyde, acetaldehyde and acetone were approx. 160%, 93%, 121% and 162%, respectively, relative to control values. Seventy-two hours after endrin administration, the liver weight/body weight and spleen weight/body weight ratios significantly increased while the thymus weight/body weight ratio markedly decreased. The results demonstrate that endrin induces dose- and time dependent alterations in lipid metabolism with the enhanced excretion of specific metabolic products in the urine. PMID- 1455429 TI - A subpopulation of 12-O-tetradecanoylphorbol-13-acetate-induced papillomas is not inhibited by retinoic acid. AB - The inhibitory effect of retinoic acid (RA) on 12-O-tetradecanoylphorbol-13 acetate- (TPA) induced mouse skin tumors was studied. Two subpopulations of tumors, small (< 2 mm) and large (> or = 2 mm) appeared after 12 weeks of cutaneous promotion by TPA (10 nmol), following initiation by application of 2 x 100 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) to the skin. RA in the doses of 17 and 34 nmol, prior to each TPA treatment inhibited (P < 0.05) the formation of small tumors at 12 weeks of promotion. However, RA in either dose did not inhibit the formation of large (> or = 2 mm) tumors. Ten weeks following withdrawal of all treatments, the number of large tumors persisted in a significantly (P < 0.05) higher number as compared to small tumors in all groups. Our results provide evidence for the existence of tumor subpopulations with a differential response to RA. In addition, elevated levels of metallothionein (MT) expression were demonstrated in papillomas induced by TPA, 72 h after the last TPA treatment. Comparing papillomas treated with RA prior to each TPA treatment and papillomas treated with TPA only, demonstrated that the elevated MT expression in papillomas was unaffected by RA. This indicated that RA did not affect the expression of a protein that showed elevated level in TPA-induced papillomas. PMID- 1455430 TI - Characterization of the toxicity of distamycin derivatives on cancer cell lines and rat heart. AB - The cytotoxicity and cardiotoxicity of benzoyl mustard (FCE 24517) and epoxamido (FCE 24561) synthetic derivatives of distamycin A were reported in the present study. The 50% inhibiting concentration (IC50) of colony formation of FCE 24517 on human SNB-19 glioblastoma, A2780 ovarian cancer and DU 145 prostate cancer was at least three times lower than that of FCE 24561; on the same cell lines the IC50 of DXR was up to 14 and 240 times higher than that of FCE 24561 and FCE 24517, respectively. Isolated rat hearts perfused with concentrations of both derivatives equivalent to their respective IC50 values did not show any significant change in ECG parameters, contractility and coronary flow. Compared to control hearts, FCE 24517 10(-6) M induced a significant increase in PR interval, reduction in + dF/dtmax, heart rate and coronary flow, while FCE 24561 10(-6) M produced a modest but significant increase in S alpha T segment and decrease in + dF/dtmax. Rats treated with FCE 24561 3, 6 or 12 mg/kg, intravenously (i.v.), once weekly for 3 weeks had a modest increase in S alpha T segment and QRS complex duration, while a slight alteration of S alpha T segment and QRS complex duration were observed in rats given FCE 24517 1 or 2 mg/kg i.v. once weekly for 3 weeks. No cardiac histologic alterations were found in hearts from rats receiving FCE 24517 or FCE 24561. For comparison, the cardiotoxicity of doxorubicin (DXR) was evaluated in the same experimental models; perfusion of hearts with DXR 10(-6) M induced severe alterations in all parameters of the isolated hearts; the administration of DXR 3 mg/kg i.v. once a week for 3 weeks was associated with a widening of the S alpha T segment and QRS complex and cardiac histologic picture was markedly altered. In conclusion, distamycin A derivatives display elevated cytotoxicity while no substantial cardiotoxicity was observed. PMID- 1455431 TI - Individual serum bile acids as early indicators of carbon tetrachloride- and chloroform-induced liver injury. AB - Individual serum bile acids (SBA) are emerging as potentially useful early indicators of liver injury. This study was undertaken to compare the usefulness of individual SBA with the routinely used assays for detecting the effects of the hepatotoxicants carbon tetrachloride (CCl4) and chloroform (CHCl3). Serum samples were assayed for liver injury by determination of alanine aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP), bilirubin and total bile acid (by enzymatic kit). These results were compared with levels of individual SBA measured by high performance liquid chromatography (HPLC). Liver samples from CCl4-treated rats were taken for light and electron microscopic examination. The highest dose for each chemical caused increases in serum ALT and AST but not ALP. Chloroform at the highest dose increased bilirubin. Total SBA levels as assayed by the kit were elevated in response to CCl4 and CHCl3 at doses below which serum enzymes and bilirubin were increased. Some individual SBA were increased at a still lower dose for each of these two chlorinated solvents. At the lowest dose of CCl4 tested no consistent light microscopic or ultrastructural changes were found. At all the higher doses periacinar cells displayed typical accumulation of lipid droplets and degranulation and dilation of rough endoplasmic reticulum. The extent of the ultrastructural changes were dose dependent. Thus individual SBA assayed by HPLC may be considered as a very sensitive indicator of liver injury induced by the classical hepatotoxicants carbon tetrachloride and chloroform. PMID- 1455432 TI - Assessment of the immunotoxic potential of the fungicide dinocap in mice. AB - The immunotoxic potential of dinocap was evaluated in female C57BL/6J mice following in vivo and in vitro exposure to this fungicide. In in vivo studies, groups of mice were dosed by gavage with technical grade dinocap at dosages ranging from 12.5 to 50 mg/kg per day for 7 or 12 days and selected immune functions examined. Mice dosed at 50 mg/kg per day dinocap died after 4 days of dosing. Twelve days of dosing with dinocap at 25 mg/kg per day resulted in decreased thymus weights and cellularity, and increased spleen weights. No changes were observed in body weight, absolute differential peripheral leukocyte counts, the lymphoproliferative responses to B- or T-cell mitogens, the mixed lymphocyte reaction, or natural killer (NK) cell activity of spleen cells from mice exposed to dinocap. Lymphoproliferative responses to concanavalin A (Con A) and phytohemagglutinin (PHA), however, were reduced in thymocytes from mice dosed at 25 mg/kg per day dinocap. The cytotoxic T lymphocyte (CTL) response to P815 mastocytoma cells was enhanced in mice exposed for 7 days to 25 mg/kg per day dinocap. Exposure of mice for 7 days to 25 mg/kg per day dinocap also caused a significant reduction in the IgM and IgG plaque-forming cell (PFC) response to sheep red blood cells (SRBC). A time-course study indicated that dinocap-induced suppression of the IgM PFC response was due to a delay in the peak PFC response to SRBC. In vitro studies using murine thymocytes cultured with dinocap (10 micrograms/ml for 72 h) resulted in suppression of the proliferative response to Con A and PHA. Exposure of thymocytes to dinocap in vitro for as little as 30 min resulted in suppression of the mitogen-stimulated response in the absence of any apparent direct cytotoxic effect. These results suggest that dinocap alters the immune system of the mouse, however, these effects are relatively modest in terms of adverse immune function and are only seen at relatively high exposure levels. PMID- 1455433 TI - Murine strain differences in metabolism and bladder toxicity of cyclophosphamide. AB - Cyclophosphamide (CP) undergoes metabolic activation, generating phosphoramide mustard and acrolein which are believed to be responsible for the cytostatic and toxic effects, respectively. In this study, CP-induced bladder toxicity (hemorrhagic cystitis) was found to be significantly greater in the ICR than the C57BL/6N (C-57) strain of mice. Strain differences exist in the distribution of CP metabolites to the bladder, as evidenced by consistently higher levels of acrolein equivalents measured in the urine of the sensitive ICR strain. These differences may arise from strain variation in the oxidative metabolism of CP by the mixed-function oxidase system. However, intrinsic factors within the bladder may also be involved in the resistance exhibited by C-57 mice. Support for this hypothesis is provided by the significant increase in hemorrhagic response and permeability of ICR compared to C-57 bladders exposed to equivalent levels of acrolein by intravesicle instillation. Basal protein thiol levels were higher in C-57 than in the ICR strain. However, the effects of acrolein on protein thiol content did not correlate with toxicity suggesting that these groups are not the critical targets for CP-induced bladder injury. PMID- 1455434 TI - Silicone implants and systemic immunological disease: review of the literature and preliminary results. AB - Silicone has been utilized as an implant in reconstructive surgery. For years, silicone has been considered to be biologically inert and essentially harmless. Several studies and case reports show that female patients treated with silicone implants developed a systemic disease associated with immunological abnormalities. Removal of the silicone implants was associated with recovery and resolution of the immune abnormalities. Recently, specific antibodies to silicone have been isolated in children with silicone implants. Additionally, immunological abnormalities and high incidence of systemic progressive sclerosis in patients with silicone implants or injections further support the notion that silicone is not biologically inert, and can cause a syndrome of a systemic disease and immunological abnormalities. The specific mechanisms and duration of the latency period is not yet fully understood. PMID- 1455435 TI - Immune alteration associated with exposure to toxic chemicals. AB - Immunological abnormalities including lymphocyte subset, lymphocyte immune functional assays, chemical antibodies, and different markers for autoimmune response were examined in individuals exposed to a variety of chemicals in computer manufacturing plants. A comparison of 289 individuals exposed to chemicals to 120 controls revealed that exposed individuals had a significantly higher percentage with either increased or decreased T helper/T suppressor ratios. In addition, the individuals with abnormal T4/T8 ratios demonstrated significant elevation in chemical-hapten antibodies. Therefore, 87 exposed subjects with abnormal T4/T8 ratios were selected for further evaluation by lymphocyte phenotypic expression and T cell, B cell, NK activity, and autoimmune markers, and were compared to 60 controls. The comparison of exposed individuals with controls indicated elevation of T cell (CD3), B cell (CD19), and activated T cell (CD10, CD15, CD26, CD38), suppressed T cell and B cell function decreased or increased NK cell cytotoxic activity. Autoimmunity due to chemical exposure was evidenced by elevation of TA1 phenotype frequencies and presence of rheumatoid factor, immune complexes, ANA, and anti myelin basic protein antibodies. We conclude that chemical exposure may induce immune abnormalities including immune suppression and autoimmunity. PMID- 1455436 TI - Effects of tetrachloroethylene on hepatic and splenic lymphocytotoxic activities in rodents. AB - The industrial solvent tetrachloroethylene (TCE) is a liver carcinogen in experimental animals but is without significant genotoxicity. Presumably some nongenotoxic mechanism accounts for its cancer-causing effects. We have therefore investigated the effects of TCE on splenic and hepatic lymphocytotoxic activities in Sprague-Dawley rats and B6C3F1 mice, following in vivo and in vitro exposure to TCE. Natural killer (NK), natural cytotoxic, and "natural P815 killer" activities were measured in liver- and spleen-derived immune cells. Humoral and T cell mitogenesis were assayed in lipopolysaccharide and Con-A-stimulated splenic cells, respectively. TCE administration in vivo did not significantly alter the various immunological parameters assessed, while in vitro exposure to TCE inhibited natural cytotoxic activity from liver and spleen in mice and rats. NK and "natural P815 killer" activity in rat cells exposed in vitro to TCE were also inhibited. Thus, TCE is capable of directly inhibiting natural lymphocytotoxic activity, which is indicated by these in vitro effects. While an inhibitory effect was not observed when immune cells were isolated from in vivo treated animals, the in vitro data do support the possibility that a direct inhibition of natural immune function may play some role in the carcinogenic effects of TCE in experimental mice. PMID- 1455437 TI - A study of the carcinogenicity of glycidol in Syrian hamsters. AB - The industrial chemical glycidol is a directly acting mutagen and a broadly acting carcinogen in rats. It was administered to Syrian golden hamsters (20 male and 20 female) by gavage of 12 mg twice a week for 60 weeks. The total dose per animal was 1.45 g or 20 mmol. Survival was not different from control hamsters treated with corn oil/ethyl acetate. Of the treated males, 9 had tumors and 13 of the treated females had tumors, some of which were adrenal cortex tumors seen in controls. More tumors were seen in the glycidol-treated hamsters than in controls, but the spleen was the only notable target organ and the number of animals with spleen hemangiosarcomas was small. Glycidol appeared to be less carcinogenic in hamsters than in rats or mice. PMID- 1455438 TI - Does nitrogen dioxide exposure increase airways responsiveness? AB - A number of reports have suggested that exposure to nitrogen dioxide (NO2) may cause increased airways responsiveness (AR). Twenty studies of asthmatics and five studies of healthy subjects exposed to NO2 were used to test this hypothesis using a simple method of meta-analysis. Individual data were obtained for the above studies and the direction of change in AR was determined for each subject. Only studies with available individual data were used. Subjects from these studies whose directional change in AR could not be determined were excluded. The fraction of positive responses (i.e. increased AR) was determined for all subjects within a group and tested for significance using a sign test. Data were also grouped according to NO2 concentration and by whether the exposure included exercise. There was an overall trend among asthmatics for AR to increase (60%) but this was primarily due to increased AR seen in resting exposures (70%). Among healthy subjects AR also increased with NO2 exposure but only at concentrations above 1.0 ppm. This analysis suggests that NO2 exposure causes increased airway responsiveness in healthy and asthmatic subjects but that exercise during exposure may modify this response in asthmatics. PMID- 1455439 TI - The effect of duration of exposure on sulfuric acid-induced pulmonary function changes in asthmatic adolescent subjects: a dose-response study. AB - To evaluate the pulmonary effects of varying doses of sulfuric acid, adolescent subjects with asthma were exposed to 35 or 70 micrograms/m3 sulfuric acid for 45 or 90 min. Exposure was carried out during intermittent moderate exercise. The pulmonary functions measured before and after exposure were FEV1, FVC, and total respiratory resistance. The 45 min exposures were associated with larger decreases in FEV1 (-6% or -3%) than the 90 min exposures (-1% or +2%). Analysis of variance of the change in FEV1 among the exposures revealed that the 45 min exposure to 35 micrograms/m3 was significant (p = 0.03). The p value for 45 min exposure to 70 micrograms/m3 was not significant (p = 0.08). Using analysis of variance, neither of the 90 min exposures was associated with a significant decrease in FEV1 compared to air exposure. Also, none of the changes in FVC or RT was significant. When baseline to post-exposure changes were compared for each of the five test atmospheres using paired t tests, both of the 45 min exposures were associated with statistical significance (p < 0.001 for 35 micrograms/m3 and p < 0.005 for 70 micrograms/m3). This baseline to post exposure change was not statistically significant for the 90 min exposures. The reason for the lesser effect on pulmonary function at increased exposure duration is not known; it may be due to changes in either varying deposition patterns or changes in buffering capacity of the cells lining the airways. With respect to individual sensitivities to H2SO4, the data showed a significant consistency across test atmospheres. PMID- 1455440 TI - Human exposure assessment. I: Understanding the uncertainties. AB - Exposure estimates produced using predictive exposure assessment methods are associated with a number of uncertainties that relate to the inherent variability of the values for a given input parameter (e.g., body weight, ingestion rate, inhalation rate) and to unknowns concerning the representativeness of the assumptions and methods used. Despite recent or ongoing consensus-building efforts that have made significant strides forward in promoting consistency in methodologies and parameter default values, the potential variability in the output exposure estimates has not been adequately addressed from a quantitative aspect. This is exemplified by remaining tendencies within federal and state agencies to use worst-case approaches for exposure assessment. In this study, range-sensitivity and Monte Carlo analyses were performed on several different exposure scenarios in order to illustrate the impact of the variability in input parameters on the total variability of the exposure output. The results of this study indicate that the variability associated with the example scenarios range up to more than four orders of magnitude when just some of the parameters are allowed to vary. Comparison of exposure estimates obtained using Monte Carlo simulations (in which selected parameters were allowed to vary over their observed ranges) to exposure estimates obtained using standard parameter default assumptions demonstrate that a default value approach can produce an exposure estimate that exceeds the 95th percentile exposure in an exposed population. PMID- 1455441 TI - Human exposure assessment. II: Quantifying and reducing the uncertainties. AB - Alternative methods of human exposure assessment that reduce and/or allow quantification of the uncertainties associated with exposure estimates are surveyed and illustrated. These alternative approaches include (1) use of more appropriate exposure parameter default values rather than values that result in extreme exposure estimates; (2) incorporation of time-activity data to better define appropriate exposure duration values; (3) the use of reasonable exposure scenarios rather than the traditional Maximally Exposed Individual (MEI) approach; (4) the use of stochastic approaches such as Monte Carlo-based and information analysis-based methods; (5) use of bivariate analysis to identify the extent to which interdependencies between different exposure parameters affect the distribution of exposure estimates; (6) use of less-than-lifetime exposure and risk assessment; and (7) incorporation of physiological considerations relevant to absorbed dose estimation, including route-specific impacts, use of improved absorption factors, and application of pharmacokinetic models. Other ways to improve the exposure assessment process, including assuring statistical equivalency in comparing different exposure estimates and incorporation of sensitive subpopulation considerations are also discussed, as are key research needs. PMID- 1455442 TI - Commentary on 'Isolated cells in the study of the molecular mechanisms of reperfusion injury' by H. de Groot. PMID- 1455443 TI - Isolated cells in the study of the molecular mechanisms of reperfusion injury. AB - Isolated cells make it possible to study mechanisms of cell and tissue injury under well-defined conditions, including the interaction of different cells in coculture experiments. Isolated cells, either in suspension or in monolayer cultures, have also been used to study the mechanism of reperfusion injury--in this case better termed as reoxygenation injury in view of the experimental approach taken. In hepatocytes, Kupffer, and endothelial cells, reoxygenation injury resulted in necrosis primarily mediated by reactive oxygen species released by various sources such as mitochondria (hepatocytes) and NADPH oxidase (Kupffer cells). In contrast, contracture was a characteristic feature of reoxygenation injury occurring in cardiomyocytes without loss of cytosolic enzymes. Beside reactive oxygen species, Kupffer cells were activated to release prostanoids and a decrease in endothelial cell-mediated fibrinolysis occurred upon reoxygenation. Reoxygenation injury in endothelial cells was significantly increased when neutrophils were added at the time of reoxygenation, presumably due to additional generation of reactive oxygen species and the release of proteases. As exemplified for the liver, these experiments suggest a mechanism of reperfusion injury in which the various cell types of a given tissue differ significantly in their response to hypoxia-reoxygenation but in which they interact with each other in a complex pathobiochemical network via various mediators such as cytokines, and tissue damaging effector molecules such as reactive oxygen species. Future experiments with isolated cells will allow detailed analysis of the underlying molecular mechanisms. PMID- 1455444 TI - Comparison of open and blind histopathologic evaluation of hepatic lesions. AB - This paper explores the controversy among scientists on whether microscopic evaluation of tissue slides should be done in an open or blind fashion. Definitions are given and discussed that provide a better focus to the problem. An experiment was conducted in which hepatocellular degeneration and necrosis in rats were assessed both openly and blindly. The results indicate that 'simple bias' is present when the slides are read openly. Valid comparisons among treatment groups are possible in the presence of simple bias, provided appropriate control groups have been incorporated into the experimental design. PMID- 1455446 TI - Teratological assessment of glutaraldehyde in rats by gastric intubation. AB - Pregnant rats were given glutaraldehyde (GA) by gastric intubation at a dose of 0, 25, 50 or 100 mg/kg on days 6-15 of pregnancy. Maternal toxicity occurred in the 100 mg/kg group as evidenced by a significant increase in maternal death and a significant decrease in maternal body weight gain and food consumption. A significantly lowered fetal weight was also found in the 100 mg/kg group. No significant change induced by GA was detected in the incidence of postimplantation loss. Morphologic examinations of fetuses revealed no evidence of teratogenicity of GA. It could be concluded that GA has no teratogenic effects on rat offspring even at a dose which induced severe maternal toxicity. PMID- 1455445 TI - Zinc and copper in tissues of rats with blood hypertension induced by long-term lead exposure. AB - Male Sprague-Dawley rats received for 14 months 0, 15, 30 and 60 micrograms/ml of lead in drinking water. Both blood pressure and tissue lead were augmented with a dose-response effect, while cardiac inotropism was increased only in the rats treated with 60 ppm of lead. In the exposed animals, zinc and copper were unchanged in kidneys and testicles and augmented in the brain, while copper, but not zinc, was reduced in the heart. These data suggest a possible relation between the modifications of copper and zinc metabolism and the effects of lead on cardiovascular homeostasis. PMID- 1455447 TI - Protection of B cells against the effect of alloxan. AB - Alloxan induces diabetes in laboratory animals through the destruction of the endocrine pancreatic B cells. The mechanism of alloxan toxicity is still obscure. This study was conducted to investigate the effects of superoxide dismutase (SOD) or reduced nicotinamide adenine dinucleotide (NADPH) treatment on the B cells in isolated rat islets prior to alloxan treatment. Islets were treated with SOD (1000 U) or 0.1 mM NADPH for 10 min followed by alloxan treatment (0.18 mg) for 5 min. Insulin secretion was studied in samples incubated for 60 min in media supplemented with glucose (1.8 mg/ml). Morphological examinations were conducted on fixed samples after the alloxan treatment. SOD significantly protected the islets from the cytotoxic effect of alloxan. Although alloxan decreased insulin secretion to 35% of the control, SOD increased this level to 73% of the control values. NADPH did not provide any protection to the islets. Insulin secretion from islets treated with NADPH and alloxan was not different from that after alloxan treatment alone. Morphological changes were observed in the islets treated with alloxan alone or alloxan in the presence of NADPH. Islets exhibited multiple cellular necrosis, marked degranulation and extensive vesiculation of the endoplasmic reticulum and Golgi complex. Mitochondrial enlargement with disrupted cristae and mitochondrial ruptures were prominent. However, islets treated with SOD and alloxan were similar to the control except for the enlarged mitochondria. The increased insulin secretion from islets treated with SOD and alloxan reinforces the free radical hypothesis of alloxan toxicity. The markedly enlarged mitochondria was one of the targets through which alloxan destroyed the B cells. PMID- 1455448 TI - Ganglioside GM1 counteracts the enhancing effects of subacute toluene exposure on apomorphine-induced locomotor activity. AB - Previous studies indicate that subacute toluene exposure enhances the effects of postsynaptic doses of apomorphine on locomotor activity in the rat. We have now studied the effects of the ganglioside GM1 on toluene-affected apomorphine induced (1 mg/kg, s.c.) locomotion, motility, and rearing. Treatment with GM1 (10 mg/kg, i.p., 1 h before exposure) was found to counteract or even reverse the enhancing effect of toluene on apomorphine-induced locomotion and rearing, but had similarly to toluene no significant effects on apomorphine-induced motility or on spontaneous locomotor activity. The antagonistic effects of GM1 may be due to its ability to block toluene-induced changes in D2 receptor binding. PMID- 1455449 TI - In vitro cytotoxicity of methylated phenylenediamines. AB - The acute cytotoxicities of methylated phenylenediamines (PDs) were evaluated with the neutral red assay, using BALB/c 3T3 mouse fibroblasts as the bioindicators. When the test agents were grouped according to their degree of methylation, good correlations were noted between their in vitro cytotoxicity and their in vivo myotoxicity to experimental animals, as well as to their in vitro autoxidation rates. For test agents of comparable methylation, the sequence of potency was ring-methylated p-PD > N-methylated p-PD >> N-methylated o-PD > N methylated m-PD. PMID- 1455450 TI - Liver thymidine kinase activity after cadmium-induced hepatotoxicity in rats. AB - Intraperitoneal (i.p.) administration of a cadmium (Cd) salt at concentrations of 1.0, 2.5 and 4.0 mg CdCl2/kg body wt. caused severe liver injury in rats 24 h after administration. The toxic effects were most evident in the intermediate dose of 2.5 mg. Thymidine kinase (TK), the key enzyme of the salvage pathway of DNA biosynthesis, was affected in all Cd-treated groups. TK activity presented lower values at the highest Cd-induced hepatotoxicity. PMID- 1455451 TI - In vivo-in vitro replicative DNA synthesis (RDS) test using perfused rat livers as an early prediction assay for nongenotoxic hepatocarcinogens: I. Establishment of a standard protocol. AB - To establish a standard protocol for an in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test using male F344 rats for screening nongenotoxic (the Ames-negative) hepatocarcinogens, experimental conditions were examined. After treatment with three model hepatocarcinogens, isolated hepatocytes showed highest RDS incidences when plated at a density of 5 x 10(4) cells/ml. Spontaneous RDS incidences in hepatocytes from rats aged 9 weeks or older showed a constant value. The use of hepatocytes from 9-week-old rats at the 5 x 10(4) cells/ml plating density was therefore determined as the standard. Based on the distribution of mean spontaneous RDS incidences over 105 additional experiments (0.4 +/- 0.18%, with SEM), an RDS incidence of over 1% was adopted as the criterion for a positive response in our rat liver RDS test. PMID- 1455452 TI - In vivo-in vitro replicative DNA synthesis (RDS) test using perfused rat livers as an early prediction assay for nongenotoxic hepatocarcinogens: II. Assessment of judgement criteria. AB - To better establish in vivo-in vitro hepatocyte replicative DNA synthesis (RDS) test using male F344 rats as a screening assay for nongenotoxic (the Ames negative) hepatocarcinogens, judgement criteria were assessed after single-gavage treatment with seven model compounds. The profiles of RDS induction by the compounds were analysed in terms of both time-course and dose-dependence. Our data reveal that a value of 2% or more for RDS incidence should be judged as positive and that of less than 1% RDS incidence as negative using maximum tolerance dose (MTD) concentrations in time-course experiments at 15, 24, 39, 48 and 63 h. In the case of an incidence value between 1 and 2%, the finding of a clear dose-dependence was considered to justify the conclusion of a positive effect for 1/4 MTD, 1/2 MTD, MTD and 2 x MTD at a fixed time. The established judgement criteria are planned for introduction in detection of nongenotoxic hepatocarcinogens (the Ames-negative carcinogens) using the RDS test. PMID- 1455453 TI - DNA damaging activity of cadmium in Leydig cells, a target cell population for cadmium carcinogenesis in the rat testis. AB - To clarify the mechanism by which Cd initiates rat testicular cancer, the ability of Cd or H2O2 to induce DNA single strand breakage was evaluated in testicular Leydig cells using a simple and rapid DNA precipitation method. Effects of Cd, Fe, Zn and Ca on the oxidant-induced DNA damage and effects of reduced glutathione (GSH) on the genotoxicity caused by the peroxide and/or Fe were also assessed. H2O2 induced strong DNA single strand breakage. Cd alone did not exhibit such a genotoxicity nor did it enhance the peroxide-induced DNA damage. Ca and Fe(II) potentiated the oxidant-induced DNA single strand breakage, while Zn partially protected cells from the oxidative damage of DNA caused by the peroxide. GSH attenuated single strand breaks of DNA brought about by H2O2 and/or Fe. These results suggest that the initiation of carcinogenesis in the rat testis by Cd is triggered by active oxygen species such as H2O2, which is generated by the metal exposure, rather than by a direct genotoxicity of Cd. The oxidant mediated initiation is clearly a complicated event accomplished by multiple factors. PMID- 1455454 TI - Aromatase and testosterone fatty acid esters: the search for a cryptic biosynthetic pathway to estradiol esters. AB - The estradiol fatty acid esters (lipoidal derivatives, LE2) are extremely potent estrogens that accumulate in fat, including fat of menopausal women. These steroidal esters are protected from metabolism and are converted to the free, biologically active steroid through the action of esterases. Previous studies have shown that biosynthetic pathways in the adrenal gland exist in which steroid fatty acid esters are substrates. This led us to determine whether a cryptic aromatase pathway exists in which testosterone esters could be converted directly into LE2. We tested a representative fatty acid ester, testosterone stearate, both as an inhibitor and as a substrate for the aromatase enzyme from human placental microsomes. This ester had neither activity. In addition, we tested [1 beta-3H]testosterone acetate as a substrate for this enzyme complex, measuring the production of 3H2O as evidence of aromatization. Although the rate of reaction was considerably slower than that of testosterone, 3H2O was produced. However, when [2, 4, 6, 7-3H]testosterone acetate was incubated and the steroidal products isolated, we found that hydrolysis of the substrate had occurred. Both [3H]-labeled testosterone and estradiol were found, and very little if any [3H]estradiol acetate was formed. Thus, we conclude that an aromatase pathway involving testosterone esters does not exist and that the sole source of LE2 is through direct esterification of estradiol. PMID- 1455455 TI - Chromatographic and mass spectrometric characteristics of 20-dihydroaldosterone. AB - The 20 alpha-reduced derivative of aldosterone, 20 alpha-dihydroaldosterone, was needed as reference compound in order to continue the studies on 18-hydroxylation in the Y-1 adrenal cell line. It was obtained by reduction of aldosterone with sodium borohydride. Analysis of the products of the reaction as methoxime trimethylsilyl (MO-TMS) derivatives by gas chromatography (GC) and GC-mass spectrometry (GC-MS) showed three possible forms of the compound. Their identification was confirmed by comparison with the products obtained by stereospecific reduction of aldosterone using 3 alpha,20 beta-hydroxysteroid dehydrogenase. Chromatographic behavior and mass spectra are given for the three forms of 20 alpha-dihydroaldosterone as the MO-TMS derivatives; that is, the 18 aldehyde, the 18,11 beta-hemiacetal, and the 11 beta:18,18:20 alpha-acetal. The possible origin of these different forms is discussed as a function of these results and of the results obtained by complementary analysis on high-performance liquid chromatography. PMID- 1455456 TI - Production and specificity of antisera raised against 25-hydroxyvitamin D3-[C-3] bovine serum albumin conjugates. AB - In order to obtain specific antisera for use in the enzyme immunoassay of 25 hydroxyvitamin D3, three hapten-carrier conjugates having different lengths of bridges at the C-3 position were prepared from 25-hydroxyvitamin D3 by coupling with bovine serum albumin using the active ester method. The specificity of anti 25-hydroxyvitamin D3 antisera elicited in rabbits was tested by a cross-reaction study with closely related secosterols and by measuring the plasma levels of 25 hydroxyvitamin D3 by means of radioimmunoassay using tritium-labeled antigen. The results indicated that the specificity of the antisera obtained is higher than that of vitamin D-binding protein, and that some of these antisera are suitable for enzyme immunoassay. PMID- 1455458 TI - X-ray structure analysis of 3,11,17-trioxoandrostane-5 alpha-carbonitrile and of 17 alpha-ethoxycarbonyloxy-3-oxoandrost-4-ene-17-carbonitrile. AB - The crystal and molecular structures of the title compounds were determined by x ray diffractometric analysis. Torsion angles and puckering parameters are reported for both compounds. In 1 the 5 alpha-cyano group influences the A-ring conformation. The carbonate ester 3 crystallizes in the monoclinic P2(1) space group with two molecules (I and II) in the asymmetric unit. The D-ring conformation is to some extent different between I and II. PMID- 1455457 TI - Effects of carbenoxolone administered acutely to adrenalectomized rats (in vivo) on renal and hepatic handling of corticosterone by 11 beta-hydroxysteroid dehydrogenase. AB - The in vivo effect(s) of carbenoxolone (CS) on renal 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), hepatic 11 beta-OHSD, and 5 beta-reductase enzymatic activity was investigated, under conditions previously shown to confer mineralocorticoid (MC)-like activity on the glucocorticoids cortisol and corticosterone; it has been suggested that this Na+ retention is linked to inhibition of renal 11 beta-OHSD. The results show that acute administration of CS [2.5 mg/rat for 0.5 or 2 hours; and 10 or 25 mg/rat for 2 hours subcutaneously (sc)] to rats caused no inhibition of 11 beta-OHSD activity in kidney homogenates, minces, and microsomes when compared with controls. However, addition of 50 nM CS to the incubation medium completely inhibited the 11 beta OHSD activity in kidney homogenates and microsomes (from controls or CS-injected rats). In contrast, hepatic microsomal 11 beta-OHSD was significantly inhibited after in vivo treatment with CS (P < 0.05) using 2 microM and 50 microM corticosterone, as was 5 beta-reductase (P < 0.05) using 4 microM corticosterone as substrate. However, chronic glycyrrhizin administration (15 mg/rat/day sc for 14 days) significantly inhibited renal 11 beta-OHSD activity when assayed in minces or homogenates. Thus, it appears that when CS is administered acutely, its effects are primarily on hepatic 11 beta-OHSD and 5 beta-reductase with no inhibition of renal 11 beta-OHSD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455459 TI - Estrogen metabolism, not biosynthesis, in rabbit articular cartilage and isolated chondrocytes: a preliminary study. AB - Because serum estrogen levels are associated with the presence of osteoarthritis, and cartilage tissue is known to contain estrogen receptors, it is of interest to determine the extent to which estrogen is biosynthesized and/or metabolized in cartilage tissue or isolated chondrocytes. In this preliminary study, using a sensitive assay method, estrogen synthetase (aromatase) was undetectable in articular cartilage or isolated chondrocytes in culture from immature female rabbits. However, estrogen metabolism, specifically estrogen 17 beta hydroxysteroid dehydrogenase activity, was detected in homogenized cartilage tissue, and at substantially higher specific activities in freshly isolated chondrocytes. These fresh chondrocytes, assayed in culture without any exogenous cofactor, demonstrated a significantly higher activity for converting the weak estrogen, estrone, to the more potent estrogen, estradiol. Chondrocytes grown to confluence in culture had very low estrogen 17 beta-hydroxysteroid dehydrogenase specific activity. Homogenized cartilage tissue, tested only with added NADPH as cofactor, also showed a preference for estradiol as the principal product, but this may have been primarily due to the use of reduced cofactor. If subsequent experiments confirm the presence of estrogen 17 beta-hydroxysteroid dehydrogenase activity, and its preference for converting estrone into estradiol, in human cartilage tissue and chondrocytes, this could have substantial implications in the estrogen dependency of osteoarthritis. PMID- 1455460 TI - Convenient synthesis of 18-hydroxylated cortisol and prednisolone. AB - 18,20-Epoxy-11 beta,17 alpha,20 beta,21-tetrahydroxypregn-4-en-3-one was synthesized by the application of hypoiodite reaction to the cortisol acetonide. The intermediary 18-iodo derivative was converted to the 11-oxo steroid by chromic acid prior to silver ion-assisted solvolysis. Removal of the protective group with hydrochloric acid was finally carried out to give the desired 11 beta,17 alpha,18,21-tetrahydroxypregn-4-ene-3,20-dione as the hemiacetal form. 18,20-Epoxy-11 beta-17 alpha,20 beta,21- tetrahydroxypregna-1,4-dien-3-one was also prepared from prednisolone through a similar reaction sequence. PMID- 1455462 TI - Novel procedure for the preparation of 1 alpha,3 beta-dihydroxy-2 beta-tritiated steroidal compounds. PMID- 1455461 TI - Administration of pregnenolone and dehydroepiandrosterone to guinea pigs and rats causes the accumulation of fatty acid esters of pregnenolone and dehydroepiandrosterone in plasma lipoproteins. AB - Steroids were administered continuously to guinea pigs and rats using subcutaneously applied silastic tubing implants, and the effects on circulating steroid and steroid conjugate levels were monitored. Using implants filled with pregnenolone, we observed that pregnenolone had a marked effect on increasing the levels of its fatty acid-esterified derivative, while dehydroepiandrosterone releasing implants produced a rise in circulating nonconjugated dehydroepiandrosterone, androst-5-ene-3 beta,17 beta-diol, androstenedione, testosterone, and lipoidal derivatives of both dehydroepiandrosterone and androst 5-ene-3 beta,17 beta-diol. Implants filled with androstenedione produced a 20 fold increase in plasma androstenedione levels relative to untreated controls and a corresponding five-fold increase over control testosterone levels. No fatty acid-esterified derivative of testosterone could be detected within the plasma. Lipoproteins were isolated from both rats and guinea pigs treated with implants filled with pregnenolone or dehydroepiandrosterone. The steroid and steroid fatty acid esters present in each fraction were analyzed, revealing that approximately 75% of all the fatty acid esters of pregnenolone recovered in the lipoproteins was localized within the high-density lipoprotein (HDL) fraction of both guinea pig and rat plasma. Similarly, lipoidal dehydroepiandrosterone was found associated predominantly with the low-density lipoprotein and HDL fractions in the guinea pig, while in the rat this steroid conjugate was exclusively within the HDL fraction. High-density lipoprotein-incorporated tritiated pregnenolone fatty acid esters and dehydroepiandrosterone fatty acid esters were injected into castrated male guinea pigs to study the fate of these complexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455463 TI - Studies on anabolic steroids. 10. Synthesis and identification of acidic urinary metabolites of oxymetholone in a human. AB - Two major unconjugated acidic metabolites of oxymetholone (17 beta-hydroxy-2 hydroxymethylene-17 alpha-methyl-5 alpha-androstan-3-one, 1), namely, 17 beta hydroxy-17 alpha-methyl-2,3-seco-5 alpha-androstane-2,3-dioic acid (2) and 3 alpha,17 beta-dihydroxy-17 alpha-methyl-5 alpha-androstane-2 beta-carboxylic acid (6a), were detected by gas chromatography/mass spectrometry in urine samples collected after oral administration of 1 to a human volunteer. Reference steroid 2 was synthesized and identified. The identification of urinary metabolite 6a was based on the synthesis of its stereoisomers and the isomerization of the methyl ester 6b to its 2-epimer, 3 alpha,17 beta-dihydroxy-17 alpha-methyl-5 alpha androstane-2 alpha-carboxylic acid methyl ester (9b). The mechanisms accounting for the formation of these acidic metabolites are discussed. PMID- 1455464 TI - Antihormonal properties of some new A-homo-B, 19-dinor steroids of the androstane series. AB - On solvolysis of Westphalen-type steroids with a leaving group in the position 6 beta (e.g., 2), products of elimination (followed by rearrangement and fragmentation of the steroid skeleton) were prepared (e.g., 4 and 5). These products were subsequently converted to suitable analogs of the compound, which has been reported to promote hair growth (1). Compounds 11 to 13 exhibited strong antiandrogenic activity in vivo; however, this activity could not be interpreted either in terms of inhibition of 5 alpha-reductase or by strong binding to an androgen receptor. PMID- 1455465 TI - [The significance of developmental anomalies of the thyroid cartilage for the practice of forensic medical expertise]. AB - The authors discuss developmental abnormalities of the thyroid cartilage and its injuries in blunt injuries of the neck. Basing on two cases, they describe developmental abnormalities (no joining between the superior horn and the lamina or complete absence of one of the superior horns) that during autopsies were considered, to be resultant from injuries. PMID- 1455466 TI - [The diagnosis of pulmonary tuberculosis in the forensic medical study of cadavers]. AB - Presents analysis of cases when pulmonary tuberculosis was diagnosed during autopsy by forensic medical experts. Before death the patients were not registered at tuberculosis control centres and were administered no treatment for tuberculosis. PMID- 1455467 TI - [A schematic representation of the thoracic skeleton for the analysis of multiple fractures]. AB - A scheme of the thoracic skeleton (a superior projection) is suggested for practical forensic medical evaluation. The scheme presents concentrically arranged costal arches connected to the image of the breast bone and the thoracic portion of the spine, with the ordinal numbers of the ribs, vertebrae, and anatomic lines. Special marks indicate rib fractures and other associated signs (repeated injuries, bleedings, whether the injury was inflicted in life or was postmortem, etc.). After the scheme is filled in, one may analyze a three dimensional image of the injuries to determine the site and direction of an external exposure and its order. PMID- 1455469 TI - [The forensic medical determination of the time of occurrence of subdural hemorrhages in the acute period of fatal craniocerebral trauma]. AB - Presents the results of spectrophotometric and histologic examinations of subdural bleedings, meninges and brain matter in the acute period of a lethal craniocerebral injury. Discusses the possible use of a complex of histologic and biochemical studies in determination of the period elapsed since the injury. PMID- 1455468 TI - [The forensic medical expertise of fatal mechanical trauma in cases of methane and coal dust explosion in a mine]. PMID- 1455470 TI - [A clinico-morphological analysis of the traumatic substrates to cerebral injuries in different inertial loads on the brain]. AB - The relationships between the inert tension of the head and the morphologic substrates of brain injuries were under study. A comparative clinical and morphologic analysis of lethal contusion and axonal injuries underlie this investigation. Differences in the neurologic semeiotics and CT data in such injuries are presented. The authors discuss the mechanisms of the physical processes in the skull, resulting in focal and diffuse injuries of the brain. Quantitative assessment of the traumatic cerebral substrates is given and relations of these parameters to the conditions of the head trauma (the direction of the external injurious factor action) and the clinical picture are shown. The results of this study may be useful in establishing some circumstances of craniocerebral injuries. PMID- 1455471 TI - [The chemical action of gun powder gases on biological tissues in a point-blank shot]. AB - Chemical effect of gun powder gas on the biologic tissues manifests by red-brown staining of the tissues, mainly at the expense of methemoglobin and sulfhemoglobin. Scarlet staining of the tissues at the edges of gun-shot wounds is not a specific marker of a shot made from a short distance; it may emerge several hours after wounding at the expense of hydroxy-hemoglobin and is not at all related to the chemical effect of gun powder gas. The conditions conducive to scarlet staining are an open wound permitting free oxygenation by air oxygen and hemoglobin transfer from the injured red cells into blood plasma and adjacent tissues. PMID- 1455472 TI - [The supplementary signs of strangulation asphyxia]. AB - Analyzes the results of forensic medical examinations of the corpses after hanging. The findings were as follows: two strangulation grooves are seen on the corpse's neck after hanging, that are similar to the grooves seen after strangulation with a loop and subsequent hanging of a corpse; the presence of bruises on the neck, along with the strangulation grooves, is indicative of a strangulation made by the hands, whereas half-moon shaped bruises may be self inflicted during hanging. PMID- 1455473 TI - [The use of high-pressure liquid chromatography for identifying barbiturates in cadaveric material]. AB - A method for chemical toxic analysis of barbiturates has been developed, making use of acetone as an extracting agent and high-pressure liquid chromatography for the identification of the isolated substances. Analysis with the use of this method is preceded by extraction and chromatographic purification. The co extractive substances do not interfere with the identification of barbiturates. PMID- 1455474 TI - [The removal and preparation of organs and tissues for transplantation]. PMID- 1455475 TI - [The determination of methylergometrin in forensic chemical research]. PMID- 1455476 TI - [The extraction of deoxypeganin from aqueous solutions with organic solvents]. AB - Studies of deoxypeganin extraction with various organic solvents have shown that up to 88% of the agent can be easily extracted by chloroform if the medium pH values are 11-12. The presence of electrolytes in deoxypeganin aqueous solutions does not influence the degree of the agent extraction with organic solvents. PMID- 1455477 TI - [The determination of acetaldehyde in biological media]. PMID- 1455478 TI - [Theophylline poisoning]. PMID- 1455480 TI - [The qualification of the degree of severity of the body injuries in closed neck trauma]. PMID- 1455481 TI - [A penetrating wound of the heart]. PMID- 1455479 TI - [Fatal outcomes in the crush syndrome]. PMID- 1455482 TI - [The forensic medical expertise of an anatomical preparation]. PMID- 1455483 TI - [The history of Claudius Galen's hydrostatic test for infant live birth]. PMID- 1455484 TI - [Phase-contrast and polarization microscopic studies of the myocardium in forensic medical practice]. AB - Describes the major acute pathologic changes in the myocardiocytes detectable by phase-contrast and polarization microscopy. Demonstrates the significance of these changes for a correct diagnosis of sudden coronary death, death from ethanol poisoning or closed injuries of the heart after blunt trauma of the chest. PMID- 1455485 TI - [Mandibular sandwich technique build up with lyophilized cartilage]. AB - High resorption rates of onlay bone grafts for augmentation of the atrophic mandible led to the invention of the sandwich technique. In Zurich the first sandwich augmentation procedure with homologous lyophilized cartilage was performed in 1982. 50% of our examined patients were operated on 5 to 8 years ago. We describe the longterm results concerning resorption (23.8% after 4.65 years) and the even integration of the lyophilized cartilage with radiologic evidence of calcification and bony incorporation, even in patients with preoperative severely compromised tissues, as in cases after osteomyelitis or radiotherapy. PMID- 1455486 TI - [Pathological changes in face and skull in acromegaly]. AB - 31 patients (mean age 52.7 years) suffering from persistent symptoms of a growth hormone producing pituitary adenoma underwent both clinical and roentgenological examinations. The results of standardized x-ray analysis of the viscero- and neurocranium were compared with those of a group of 25 healthy subjects (mean age 42.1 years): Although several remarkable changes were observed, statistically significant changes of the facial skeleton could be found only in the lower jaw. The main contribution to its elongation was given by the chin prominence and the condyle. The findings in the neurocranium could be divided in symptoms of first and symptoms of second choice. With the help of these parameters, a score was established to facilitate interpretation of early signs of acromegaly in lateral skull radiographs. Two clinical symptoms found in our patient sample have not been mentioned before in literature about acromegaly: the so-called "hanging columella" and marked changes in diameter of the canalis mandibularis. PMID- 1455488 TI - [Medicine--technology--anxiety for the future]. PMID- 1455487 TI - [Unfounded fear of amalgam]. PMID- 1455489 TI - [Vestibuloplasty with Kirschner wire fixation]. AB - We present a new method of fixation for creation of the vestibular sulcus in cases of open or closed submucous vestibuloplasty. Kirschner-wires (diameter 0.5 mm) are drilled through the mucous membrane into the bone. The wires keep the hand cut oval elastic sheets in place to adapt the mucous membrane to the periosteum at the deepest point of the vestibule respectively. Advantages of the method in comparison to other fixation techniques are discussed. PMID- 1455490 TI - [Psychology and recurrence tendency in relation to age at operation for prognathism]. AB - Within this study patients with mandibular prognathism were studied as to their psychological situation pre- and postoperatively with the help of the Freiburg Personality Evaluation Sheet. Since it was our special interest, whether psychologically it makes a big difference whether the patients were operated during the time of adolescence or after the age of twenty, the postoperative investigation was carried out with special reference to this point. Without any doubt, the correction of prognathism improved the psychological situation of the patients. It was obvious that for those patients in between fourteen and seventeen the improvement was more helpful than for those patients after the age of twenty. On the other hand the rate of recurrence was much higher within the group of those patients operated in between fourteen and seventeen (29.8%) than for those patients which were operated later than at age twenty (8%). The ideal age for the correction of mandibular prognathism must be found individually. While the operation at an early time is more helpful for the psychological situation of the patients, it must on the other hand be seen that for this age group the danger of recurrence is higher. PMID- 1455491 TI - [Comparative investigation of electrochemical corrosion in gold and palladium based alloys]. PMID- 1455492 TI - [20 years of poison law. Chemical legislation--quo vadis?]. PMID- 1455493 TI - [Late effects of different high mid-face osteotomies]. PMID- 1455494 TI - Barriers to perioperative patient teaching in Kuwait. AB - 1. Although nurses agree that perioperative instruction is an integral aspect of surgical nursing, in many hospitals, there is little evidence to show that active and planned patient teaching is being conducted. 2. Arab and non-Arab nurses differed in their perceptions about obstacles to patient teaching. Lack of time and language barriers emerged as the two outstanding barriers; lack of encouragement and support from co-nurses and patients' anxiety were considered weak barriers. 3. Failing to address these barriers and disregarding the short- and long-term benefits of structured patient teaching could lead to a new health worker, the health educator. This would further fragment patient care and weaken nurses' credibility. PMID- 1455495 TI - Death with dignity: significance of religious beliefs and practices in Hinduism, Buddhism, and Islam. AB - 1. Nurses can help individuals more readily deal with death and dying by examining cultural variations in death reactions and rituals. This helps to humanize care. 2. Caring for a dying client is a complex and challenging responsibility and requires physical, emotional, and spiritual support to ensure a peaceful and dignified death. 3. Clients turn to religion for peace and comfort during times of crisis, such as serious illness and impending death. It is necessary to understand the impact of religious beliefs and practices to provide quality holistic care. PMID- 1455496 TI - The element of care in the operating room. AB - 1. Perioperative nurses are experts in attending to imminent physiological needs of patients. However, when these needs seem paramount, focus on a patient's feelings often become a lower priority. 2. Being cared for is a basic human need. Just as perceptions of needs vary among individuals, so do caring needs. It is essential that nurses value the components of caring and demonstrate caring from a holistic perspective. 3. OR nurses can communicate caring by identifying staff to patients, providing reassuring information, monitoring self-talk, touching the patient, and responding to the patient as an individual. PMID- 1455497 TI - Laser disc decompression. AB - 1. The incidence of low back pain is a growing force in today's economy. 2. Laser disc decompression (LDD) is an effective alternative for lumbar laminectomy in those patients meeting the approved criteria. 3. LDD can be done on a same day surgery basis without the ill effects of a general anesthetic. PMID- 1455498 TI - HIV-1 symptoms similar in i.v. drug users, gays/bisexuals. PMID- 1455499 TI - Union presses for safer device. PMID- 1455500 TI - How risky is orthopedics? PMID- 1455501 TI - Device increases protection during surgery. PMID- 1455503 TI - Signal transduction: crosstalk. PMID- 1455502 TI - Write now: a guide to publishing. AB - 1. With the elimination of time constraints, fear of rejection, and lack of understanding of the publication process, effective communication and sharing of experiences and expertise among nurses can be enhanced through writing for publication. 2. Important author responsibilities, such as being aware of the number of manuscript copies to be sent with the original, typing and reference format of the journal, letters of transmittal, and acknowledgements, can be found in the journal's guidelines. 3. Understanding the publication process and learning how to use the components can lead to positive results for prospective authors. PMID- 1455504 TI - Triggering signaling cascades by receptor tyrosine kinases. AB - Growth factor receptors that are tyrosine kinases (RTKs) regulate growth and differentiation of cells in many organisms, including flies, worms, frogs, mice and humans. There has been recent progress in understanding the mechanism by which these receptors transduce signals. Worm and insect studies on RTKs have relied primarily on genetics, while the mammalian studies have employed a combination of molecular genetics and biochemistry. While many RTKs seem to have unique features, there are also many general signal transduction principles that emerge from these studies. In this review, we will focus on common signaling molecules, using RTKs from both vertebrates and invertebrates as examples. PMID- 1455505 TI - Common subunits of cytokine receptors and the functional redundancy of cytokines. AB - Several distinct cytokines often exhibit similar biological activities. The findings that high-affinity receptors for a group of cytokines with similar function share a common subunit with a critical role in signal transduction have provided a molecular basis for the functional redundancy of cytokines. Since the common subunit, together with distinct cytokine-specific receptor subunits, form high-affinity receptors, binding of one cytokine to its high-affinity receptor can be competed for by other cytokines in the same group. PMID- 1455506 TI - G proteins. AB - The family of heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) serves an essential role in transducing receptor-generated signals across the plasma membrane. Recent findings reveal unexpected functional roles for individual G protein subunits. Thus, GTP-binding alpha-subunits and the beta gamma-subunit complex can influence the activity of effector molecules independently or simultaneously, either synergistically or in opposition, to elicit a complex constellation of cellular events. PMID- 1455508 TI - Crosstalk among multiple signal-activated phospholipases. AB - Transduction of extracellular signals across the plasma membrane often involves activation of several phospholipases that generate multiple, sometimes interconvertible, lipid-derived messengers. Coordination and integration of these signal-activated phospholipases may require crosstalk between both the messengers and target protein constituents of these pathways. PMID- 1455507 TI - Signal transduction crosstalk in the endocrine system: pancreatic beta-cells and the glucose competence concept. AB - Crosstalk between intracellular signalling systems is recognized as the principal means by which a cell orchestrates coordinate responses to stimulation by neurotransmitters, hormones or growth factors. The functional consequences of crosstalk are evident at multiple levels within a given signalling cascade, including the regulation of receptor-ligand interactions, guanine nucleotide binding proteins, enzyme activities, ion channel function and gene expression. Here we focus on the pancreatic beta-cells of the islets of Langerhans to illustrate the important role crosstalk plays in the regulation of glucose induced insulin secretion. Recent studies indicating a synergistic interaction in beta-cells between the glucose-regulated ATP-dependent signalling system and the hormonally regulated cAMP-dependent signalling system are emphasized. This interaction gives beta-cells the ability to match the ambient concentration of glucose to an appropriate insulin secretory response, a process we refer to as the induction of glucose competence. The glucose competence concept may provide new insights into the etiology and treatment of non-insulin-dependent diabetes mellitus (Type II diabetes). PMID- 1455509 TI - Protein kinase C, calcium and phospholipid degradation. AB - In most cells, calcium signals are transient, while the resulting physiological responses often persist longer. The sustained activation of protein kinase C has been postulated to be essential for maintaining such cellular responses. It is becoming clear that an elaborate network involving protein kinase C, calcium and degradation of membrane phospholipids may generate several molecules that are necessary for sustaining the activation of protein kinase C itself. Multiple members of the protein kinase C family show distinct responses to calcium and the phospholipid degradation products, suggesting their unique functions in cell signalling. PMID- 1455510 TI - Control of transcription factors by signal transduction pathways: the beginning of the end. AB - Signal transduction pathways regulate gene expression by modulating the activity of nuclear transcription factors. The mechanisms that control the activity of two groups of sequence-specific transcription factors, the AP-1 and CREB/ATF proteins, are described. These factors serve as a paradigm explaining the transfer of regulatory information from the cell surface to the nucleus. PMID- 1455511 TI - The serum response element. AB - The promoters of many genes whose transcription is rapidly and transiently induced following growth factor or mitogen stimulation of susceptible cells contain a common regulatory element, the serum response element (SRE). As the transcription factors that bind the SRE and the signalling molecules that affect its activity are characterized in more detail, the major challenge is to elucidate the signalling pathways that link cell-surface receptors to the SRE, and to determine the mechanism by which signalling events modulate transcription factor activity. PMID- 1455512 TI - Signal transduction through the T-cell antigen receptor. AB - The mechanism by which ligand binding to the T-cell antigen receptor triggers the T-cell activation program has long been one of the most fascinating questions in lymphocyte biology. Here, we review recent insights into the transmembrane signaling functions of this multisubunit receptor complex. PMID- 1455513 TI - Signal transduction and the actin cytoskeleton: the roles of MARCKS and profilin. AB - MARCKS and profilin, two actin-binding proteins, are discussed to illustrate the mechanism by which extracellular signals are coupled to changes in the structure of the actin cytoskeleton. MARCKS is a filamentous actin-crosslinking protein that appears to function as an integrator of protein kinase C and calcium (Ca2+)/calmodulin signals in the regulation of actin-membrane interactions. New data suggest that profilin is activated by the coordinated action of receptor tyrosine kinases and phospholipase C-gamma 1 to stimulate the stabilization of actin filaments. PMID- 1455514 TI - Channel your energies. PMID- 1455515 TI - Protein sorting in mitochondria. AB - Most polypeptides that are imported into the mitochondrial matrix use a common translocation machinery. By contrast, proteins of the other mitochondrial compartments are imported by a variety of different mechanisms. Some of these proteins completely bypass the common translocation machinery, others use only the outer membrane components of this machinery, and still others use components of this machinery from both the outer and inner membranes. Import to the intermembrane space compartment provides examples of all three possibilities. PMID- 1455516 TI - Does hydrophobic hydration destabilize protein native structures? AB - Water in the immediate vicinity of a non-polar solute has characteristically low entropy and high heat capacity at 25 degrees C. Common opinion has been that the insolubility of such species is caused by thermodynamic changes associated with the formation of these layers of abnormal water, 'hydrophobic hydration'. Recently, however, it has been proposed instead that hydrophobic hydration favors solution of hydrocarbons, or hydrocarbon sidechains, in water and therefore promotes protein unfolding. It is argued here that available data do not convincingly support this hypothesis. PMID- 1455517 TI - The ATP-dependent glutathione S-conjugate export pump. AB - The ATP-dependent glutathione S-conjugate export pump (GS-X pump) plays a physiologically important role as a member of the 'phase III' system in xenobiotic metabolism as well as in the release of biologically active endogenous substances from cells. In addition, this export pump is potentially involved in the modulation of the antiproliferative action of certain antitumor agents. PMID- 1455518 TI - The human protooncogene ret: a communicative cadherin? PMID- 1455519 TI - How to make a glycoinositol phospholipid anchor. AB - Essentially all eukaryotic cells express proteins on their surface that are anchored by a glycoinositol phospholipid. This anchor moiety may endow such proteins with unusual properties. The definition of the biosynthetic path that constructs these anchors is now in its final stages. Mutations that interrupt this path are, remarkably, compatible with survival of cells in culture, but are associated with at least one human disease. PMID- 1455520 TI - Signal peptidases in prokaryotes and eukaryotes--a new protease family. AB - Signal peptidases remove targeting peptides from pre-proteins and play central roles in the secretory pathway, as well as in the delivery of proteins to the mitochondrial intermembrane space and to the lumen of thylakoids. The catalytic mechanism of pre-protein cleavage has long been an enigma, but recent data from site-directed mutagenesis and sequence alignment studies suggest that signal peptidases may constitute a new type of serine protease, mechanistically related to the beta-lactamases. PMID- 1455521 TI - Morbidity due to infection with Schistosoma mansoni: an update. PMID- 1455522 TI - Interaction of malarial infection and glucose-6-phosphate dehydrogenase deficiency in Muria gonds of district Bastar, central India. AB - Muria gond tribals (n = 473) from district Bastar, central India, an area known to be hyperendemic for malaria, were investigated for malarial infection and glucose-6-phosphate dehydrogenase deficiency. The frequency of G-6-PD deficiency was 21.3% among male subjects and 3.7% among females. Assay of malarial antibodies showed that seropositivity as well as the level of antibodies was significantly higher in male subjects with normal enzyme levels as compared with males G-6-PD deficiency. Females with normal G-6-PD enzyme levels too had higher seropositivity as well as level of antibodies against malaria as compared with females having G-6-PD deficiency. This suggests that G-6-PD deficiency correlates with a higher degree of resistance. PMID- 1455523 TI - Antimalarial drug sensitivity patterns in the western province of Zambia. Implications for the management of primary health care (PHC). AB - The management of acute malaria consists of chemotherapy aimed at restoring the normal function of all organs. Appropriate treatment is dependent upon extensive knowledge of the drug sensitivity patterns of the malaria parasites in the area. This is also important for chemoprophylaxis. Drug sensitivity patterns and recrudescence rates for Mongu (Western Province in Zambia) are suggestive of a likely increase in resistance to both chloroquine and sulfadoxine-pyrimethamine (Fansidar). We found RI (19.4%), RII (1.5%) and RIII (4.4%) resistance to chloroquine and RII (4.3%) resistance to Fansidar. This calls for careful consideration of treatment schedules, legislation pertaining to the distribution of drugs in the general public and alternative antimalarial control strategies. PMID- 1455524 TI - A comparative study of four serological methods for diagnosis of acute and chronic Chagas' disease in Brazilian patients. AB - Complement fixation (CF), indirect immunofluorescence (IFAT), latex agglutination (LA) and the enzyme-linked immunosorbent assay (ELISA) were applied to assess the diagnostic value of antibody determination in Brazilian patients with acute or chronic Chagas' disease. Patients with various forms of leishmaniasis and healthy individuals from the endemic region were used as specificity controls. Whereas LA, IFAT and ELISA identified 81% of acutely ill patients, CF had no diagnostic potential in this phase of the disease. In later stages CF showed a sensitivity of 69% as compared to 100% for LA, IFAT and ELISA, irrespective whether patients presented clinically as chronic asymptomatic or chronic symptomatic cases. Cross reactivity with anti-leishmania antibodies was observed in 23%, 38% and 77% of serum samples in LA, ELISA and IFAT, respectively, but not in CF. PMID- 1455525 TI - Bacteriological and serological study of pertussis in Abeokuta, Nigeria. AB - Charcoal horse blood agar is the medium of choice for isolation of Bordetella pertussis from patients with early whooping cough. Since sterile animal blood often is not available in developing countries, a field study in Nigeria was undertaken to evaluate donated human blood as supplement to charcoal agar. Out of 209 children with suspected early pertussis, 33 were culture-positive (isolation rate 16%). Out of 188 children studied serologically by enzyme immunoassay, 36 (19%) were seropositive. The satisfactory isolation rate of 16% shows that culturing for B. pertussis on charcoal human blood agar can be tried in countries, where there is no regular supply of bacteriological media with animal blood. PMID- 1455526 TI - Congenital syphilis. Diagnosis in places with limited facilities. AB - The cases of 4 newborns with congenital syphilis (CS) seen in a rural hospital in Tanzania are reported. Clinical signs may be caused by other diseases than CS and are not conclusive. Therefore, uniformity in diagnostic criteria based on clinical symptoms and serology is essential for comparative clinical and epidemiological studies in places with limited facilities. The surveillance case definition for congenital syphilis introduced by the Centers for Disease Control (CDC) in 1988 and revised in 1989 [1] offers the opportunity to report congenital syphilis not only in places with sophisticated equipment but also in places with limited facilities. PMID- 1455527 TI - Prevalence of bacterial agents of diarrhoeal disease at the National University Hospital, Singapore and their resistance to antimicrobial agents. AB - Over a 50-month period, 4,508 stool specimens from patients with diarrhoea were bacteriologically examined at the National University Hospital, Singapore. Salmonella serotypes other than the typhoid and paratyphoid bacilli were the most common finding, being isolated in 10.8% of cases. Campylobacter jejuni was unexpectedly infrequent (1.9%); Aeromonas hydrophila was found in 1.8%. No other aerobic pathogen occurred in more than 1% of cases. Clostridium difficile was sought only when requested, and was isolated from 9.6% of cases tested. Testing for enteropathogenic Escherichia coli was limited to children under 1 year old. Gentamicin was active against the greatest number of aerobic isolates, followed by chloramphenicol and cotrimoxazole. The C. difficile isolates were all sensitive to metronidazole. PMID- 1455528 TI - Febrile convulsions: factors and recurrence rate. AB - One hundred and forty-seven children admitted consecutively with their first febrile convulsion were studied to assess the influence of certain factors on the recurrence rate of seizures. The younger the age at first occurrence the more likely the recurrence rate. Those with moderate degree of pyrexia (39-39.9 degrees C) were found to be ten times more likely to have subsequent recurring convulsions compared to those with high degree of pyrexia (40 degrees C and above) or those with mild degree of pyrexia (38-38.9 degrees C). Furthermore, the recurrence rate was five times higher in first-born compared to siblings second borne or more. The overall recurrence rate was 29.3% with the frequency varying between 1 to 2 times. A male preponderance was observed. These factors might be of prognostic value in terms of risk for recurrence. PMID- 1455529 TI - Prevalence of human immunodeficiency virus-infection among pregnant women attending ante-natal clinic in Maiduguri, north-eastern Nigeria. AB - A seroepidemiological survey conducted among 1,059 pregnant women in Maiduguri, North-eastern Nigeria from September, 1988 to April, 1990 showed that 5 women or 0.47% were positive for HIV antibodies. Three of the women (0.28%) were positive for HIV-1 while 2 others (0.19%) were positive for HIV-2; this is consistent with the known fact that both viruses are active in West Africa, a sub-region of which Nigeria is part. Detailed information available on 4 of the 5 seropositive women and their husbands did not reveal any known risk factor favouring HIV-infection. In addition to the 5 confirmed seropositive women, 10 others (0.94%) gave Western blot patterns that were neither HIV-1 nor HIV-2. The significance of this observation, if any, needs to be clarified. PMID- 1455530 TI - Mouth-to-anus transit-time predicts the severity of fecal water loss in acute dehydrating diarrhea. AB - The mouth-to-anus transit time was estimated in 24 young children admitted to an outpatient rehydration unit with acute dehydrating diarrheal disease by adding an oral fecal marker (brilliant blue) to the first draught of oral rehydration solution. Transit times ranged from 30 to 242 min. There was a highly significant (logarithmic) relationship between rate of fecal output and transit time (r = 0.74; p < 0.001). Three of 24 subjects could not be rehydrated orally, were declared treatment failures, and were hospitalized for intravenous therapy. All of them had had an initial transit time of less than 50 min, and constituted three of the four subjects with this rapid rate of transit. Thus, a rapid mouth to-anus transit time had a 100% sensitivity to predict treatment failures and a 75% predictive accuracy for a "positive" test. Although our series is small, the findings suggest that fecal markers may be useful in remote areas to assist in the early detection of diarrheal episodes that cannot be managed by oral rehydration therapy. PMID- 1455532 TI - Milk macronutrient levels during the first month of term and preterm Nigerian mothers. AB - The lactose levels of the transition milk of term mothers were significantly higher compared with preterm mothers (5.87 versus 5.32 g/100 ml). The same trends were found in colostrum and mature milk. These differences were not significant. The protein contents of the colostrum in term mothers were significantly lower than in their preterm counterparts (1.80 versus 2.20 g/100 ml). Again the same trend (not significant) was showed in transition and mature milk. A significantly lower level of fat in milk of term mothers than of preterm mothers was found in all 3 types of milk (1.84 versus 2.26; 2.16 versus 2.95; 2.72 versus 3.32 in colostrum, transition milk and mature milk respectively). This study showed differences in the macronutrients measured in the different types of milk, hence term babies in Baby care units should be fed term milk and preterm babies with preterm milk. PMID- 1455531 TI - Reproduction and maternal nutrition in Madura, Indonesia. AB - The prevalence and severity of chronic energy deficiency (CED) among women of reproductive age as well as its consequences on the newborn and the mother were assessed in a longitudinal study. More than 40% of the mothers had a Body Mass Index (BMI) less than 18.5 before pregnancy, a level below which CED is considered to exist. Weight gain during pregnancy was low, on average 6.6 kg. Taking the difference between 4 week postpartum weight and pre-pregnant weight as net weight gain during pregnancy, mothers with a BMI less than 18.5 before pregnancy gained weight while those with a higher BMI lost weight. This observation suggests that the partitioning of energy to the fetus and the mother depends on the energy reserves of the mother before pregnancy. The functional significance of BMI as an indicator of CED is illustrated by its relation with birth weight. Similarly, 4 week postpartum, weight and BMI were predictive for the weight changes in the mother in the first 12 months after delivery. The groups with the lowest values gained weight, while the heaviest mothers lost weight. In view of the negative effects of CED among women of reproductive age on the infant and the mother, maternal undernutrition should receive the same attention as malnutrition among preschool children. PMID- 1455533 TI - Antinutrients content of some locally available legumes and cereals in Nigeria. AB - Plant protein is the cheapest source of protein available to mankind but unfortunately the protein is accompanied by antinutrients. The quantity of oxalate and tannin in acha, bambara groundnut, guinea corn, millet, sesame seed, soybean and tiger nut were chemically analyzed. The white variety of sesame seed and soybean have the highest oxalate and tannin contents of 8.25 mg/g and 0.15 mg/g respectively. Among the cereals the black and brown varieties of millet have the highest oxalate and tannin contents of 4.65 mg/g and 0.07 mg/g respectively. The presence of these antinutrients makes plant (especially legumes) protein partially available and of poor quality. PMID- 1455534 TI - Angioid streaks in Uganda. AB - A study on the ophthalmoscopic appearance of angioid streaks and their suspected association with local and systemic diseases among ugandan Africans is presented. In all 40 eyes of 20 patients were studied and the results indicate an interesting association with certain diseases. PMID- 1455535 TI - Painless peripheral lymphadenopathy in Nigerian children. AB - We conducted a diagnostic biopsy during a period of 8 years (January 1981 - December 1988) on 74 consecutive children (aged under 16 years) who attended the University of Calabar Teaching Hospital, Calabar, for chronic enlarged painless lymphadenopathy, with a view to determining the diseases that commonly present with this symptom in our environment. Histological diagnoses returned were predominantly tuberculosis, neoplasms and nonspecific reactive changes. Each of these conditions was evenly distributed among the entire age group. Neoplasms were mainly Hodgkins and non-Hodgkins lymphoma, with Burkitt's tumour the commonest childhood tumour in Nigeria not contributing significantly to the neoplastic lymphadenopathy. Regional enlargement rather than generalised lymphadenopathy seems to be dominant, the commonest sites of involvement being the cervical followed by the inguinal regions. Chronic lymph node enlargement appears to be rare in our environment and only a few disease conditions manifest with peripheral nodes despite the large number of infections and other inflammatory diseases in Nigerian children. PMID- 1455536 TI - A hydatid cyst at an unusual site. PMID- 1455537 TI - Trichinosis from wild boar meat in Gojjam, north-west Ethiopia. AB - An outbreak of trichinosis associated with ingestion of meat from a wild boar in Gojjam administrative region, Ethiopia, is reported. Of the 30 soldiers, 20 who ate the meat raw, became ill and 5 of them were admitted to the Armed Forces General Hospital (AFGH). Even though they presented with a typical history and clinical features the disease was not even suspected at the peripheral hospital. The diagnosis was confirmed, at the AFGH, by deltoid muscle biopsy in all the 5 cases. Trichinosis being increasingly recognized as a public health problem in Ethiopia, warrants public education and more awareness by health workers. PMID- 1455538 TI - Hernia in northern Jordan. Some epidemiological considerations. AB - This retrospective study covers the authors' experience over five years of 1,722 primary hernia repairs in 1,722 patients of all ages. An analysis of some epidemiological features is presented and discussed. Inguinal hernia was by far the commonest variety accounting for more than 84% of the total series. Regardless of sex and type of hernia, 60% of all hernias were right-sided while not more than 5% were bilateral. The male to female ratio for the entire series was 4.3:1 and 8.2:1 for the inguinal hernia group. The main findings of this retrospective study are in direct accord with other series reported in the literature. Furthermore, we suspect our results are typical of those to be found in large and comparable general community hospitals in Jordan. PMID- 1455539 TI - AIDS and women's health care in developing countries. PMID- 1455540 TI - Prevention of HIV transmission through blood transfusion in Tanzania. PMID- 1455541 TI - AIDS in children. PMID- 1455542 TI - Seroprevalence of HIV and STD in Mwanza region, Tanzania. PMID- 1455543 TI - Surgery and AIDS; safety aspects and clinical experience. PMID- 1455544 TI - Clinical and microbiological aspects of microsporidiosis. PMID- 1455545 TI - Lilalu, psychosis in Kenya the contribution of traditional and prayer healers and Western psychiatry to the social reintegration of psychotic patients. PMID- 1455546 TI - The treatment of kala-azar: old and new options. PMID- 1455547 TI - [The effect of cadmium on the survivability of colony-forming hematopoietic cells in mice exposed to x-ray irradiation]. AB - It has been reported elsewhere that in addition to enhancing the expression of metallothionein genes, the previous injection of cadmium salts into sublethally X irradiated mice increases by 10 times the number of endogenous spleen colonies. To understand the mechanism of the strong radioprotective cadmium effect donors and recipients were treated separately. It is shown that the survival of exogenous bone marrow colony-forming cells in lethally irradiated recipient remains at the control level independently of the donor cadmium treatment, whereas the injection of cadmium nitrate to recipient mice leads to the stimulation of colony formation by 1.7-1.8 times. The data allow to conclude that the cadmium effect on the survival of colony-forming hemopoietic murine cells after X-irradiation is not mediated by the enhanced expression of metallothionein genes. PMID- 1455548 TI - [A rapid method for the combined staining of chromosomal nucleolus organizer regions with silver and the differential staining of chromosomes in the laboratory mouse]. PMID- 1455549 TI - [Eukaryotes devoid of the most important cellular organelles (flagella, Golgi apparatus, mitochondria) and the main task of organellology]. AB - Comparative evidence on the lack of three important organelles (flagella, Golgi complex, mitochondria) in cells and organisms at the cellular level of organization has been summarized for all the four eukaryotic kingdoms--Protista, Fungi, Plantae and Animalia (Metazoa). It is established that in the course of evolution these organelles may undergo the total reduction. There is no cellular organelle to be regarded as universal, indispensable. There are only three main obligatory cell components--the plasmalemma, nucleus and cytoplasm (with applied cytoskeleton, cytomembranes and ribosomes). The reduction of flagella (cilia) is occurring in different taxa independent of the transition of protists from the flagellate type of locomotion to the amoeboid, gliding of metabolizing ones, and in the number of metazoan cells. The members of Protista and Fungi, which line in microaerobic or anaerobic conditions, nearly inevitably lose their mitochondria. The tendency to lose Golgi-complex is demonstrated in protists with parasitic mode of life, especially in combination with anaerobiosis. There is so far no satisfied morphological criterium that could say with certainty whether the lacking of flagella, Golgi complex or mitochondria in the low eukaryotes may be primary or secondary (as the result of reduction). Data on the composition, structure and RNA nucleotide sequences cannot be either the straight evidence. A comparative analysis of these data shows that the ribosomes of the primary eukaryotes were, presumably, of a prokaryotic type. Their eukaryotization was carried out for a long time during the evolution of the low eukaryotes (Protista and Fungi), probably, independently in different phylogenetic lines. It is unknown at what steps and in what main phylogenetic lines the three above mentioned organelles may have appeared. It is proposed to single out a special division of cytology--organellology (organoidology)--as an individual science whose main purpose may be investigation of the origination, evolution and disappearance of organelles. PMID- 1455550 TI - [The capacity for reactive DNA synthesis of the myocytes in the heart conduction system in experimental and clinical myocardial pathology]. AB - The DNA synthesis has been studied in the conductive system (CS) myocytes, compared to that in atrial and ventricular myocytes: 1) in the left ventricular myocardial infarction induced in two- and three-week-old and adult rats, 2) after isoproterenol injections to adult rats and mice, and 3) in the hypertrophied human heart. The extent of DNA synthesis reactivation was evaluated by the cumulative labeling indices in experiments with multiple 3HTdR injections to rats and mice. In the human cardiac myocyte nuclei, the DNA content was determined by the Feulgen-cytophotometry. The difference between the control and experimental mean values of the labeling indices for CS myocyte nuclei was statistically significant only for atrioventricular part of the CS in the infarcted hearts of adult rats. In the human heart CS the ability of myocytes to polyploidization varies from one cell type to another, the lowest being in nodal cells. PMID- 1455551 TI - [The structure of the reticulum of Mauthner's neurons in tadpoles of the clawed toad grown under increased gravitational force]. AB - The ultrastructure of the Mauthner cells (M-cells) and the behaviour of Xenopus laevis tadpoles, reared from eggs under increased gravity (2.9 g) which changes the activity of an afferent vestibular input, were investigated. Besides, a study was made of tadpoles after the hindbrain ablation at earlier embryonal stages which significantly altered the microenvironment of M-cells. It is shown that experimental treatments enhance the proliferation of endoplasmic reticulum and its derivatives, so called subsurface cisterns, in the subsynaptic areas. Some structural changes of the synaptic active zones and the cytoskeleton of M-cells were also noticed. It is assumed that the development of the endoplasmic reticulum promotes an intense removal of calcium ions from subsynaptic areas. The plasticity of the endoplasmic reticulum together with other ultrastructural changes apparently stipulate the adaptation of neurons to changed conditions of functioning. PMID- 1455552 TI - [A stereoscopic analysis of centrosome structure in the cells of a tissue culture under the action of energy metabolism inhibitors. I. 2,4-Dinitrophenol, deoxyglucose, sodium azide and the calcium ionophore A23187]. AB - A 30-min action of energy transfer inhibitors (2,4-dinitrophenol, deoxyglucose, azide and calcium ionophore A23187) on tissue culture cells results in a significant increase in the quantity of microtubules around the centrosome. After the action of all the inhibitors, mostly increases the number of long microtubules with free proximal end oriented towards the centrosome. It is suggested that energy transfer inhibitors may stimulate foundation of microtubules on the centrosome and stabilize free microtubules, while they exert no effect on the frequency of detachment of microtubules from the centrosome. PMID- 1455553 TI - [The production of "pure" cultures of neurons from the brain of human embryos]. AB - A method has been developed for preparing essentially pure primary cultures of neurons from 10-12 week old fetal human brain. This method is based on the 1) capacity of neurons to form multicellular aggregates, 2) cultivation in chemically defined medium, and 3) treatment with cytosine arabinoside as antimitotic agent. This procedure allowed the preparation of highly purified (95 per cent and more) neuronal aggregate cultures. Ultrastructural analysis of these cultures following one and 8 days has revealed their partial differentiation during cultivation. PMID- 1455554 TI - [The autocrine regulation of the proliferation of cell line A-549 under conditions facilitating the acidification of the culture medium]. AB - The influence of serum-free media, previously conditioned by A-549 line cells of the human lung adenocarcinoma (c-medium), on the intensity of 3H-thymidine incorporation into DNA of the same cells was studied. It was found that, depending on the duration of conditioning (2, 4 and 6 days), the c-media were obtained with corresponding values of pH--7.2, 6.9 and 6.3, in the latter case the contact inhibition of cell growth being seen. On culturing the A-549 line cells in the c-medium at pH 7.2 and 6.9, the intensity of DNA biosynthesis was shown to be 2.4 and 1.8 times higher, respectively, compared to that under condition of the fresh serum-free medium. The cell culturing in the c-medium at pH 6.3 (here and in the case of pH 6.9 c-medium the media pH were made up to 7.2 before utilization) leads to the inhibition of DNA biosynthesis intensity in the cells. It was also detected that a temporary acidification of the pH 7.2 c-medium to pH 4.0 or 2.0, using, respectively CO2 bubbling or HCl titration, caused the growth inhibiting manifestation in this medium. The results obtained testify that the carcinoma cells of A-549 line are able to secrete into the cultured medium both stimulators and inhibitors of DNA biosynthesis, with a transforming growth factor beta being of primary importance among the latter. PMID- 1455555 TI - [The regulation of DNA repair processes in mammalian cells. III. The effect of epidermal growth factor on the postradiation recovery of the cell cycle in human A 431 cells and embryonic fibroblasts]. AB - Recovery of the cell cycle in cells A 431 and in human embryo fibroblasts (EFH) differs much. Unlike EFH, A 431 cells have: 1) synchronized exit of cells from G1 into S phase after 5 Gr irradiation; 2) G2-block; 3) much less manifestation of these two phenomena in the presence of EGF; 4) a lesser effectiveness of the repair of DNA single-strand breaks. EGF stimulation of the repair of radiation induced DNA lesions, SSB in particular, may be of great importance for the postirradiation cell cycle recovery. PMID- 1455556 TI - [The effect of the conditions for connective tissue formation during posttraumatic skin regeneration in rats on the adhesive properties of the epidermal cells]. AB - A cicatrix formed in the process of posttraumatic skin regeneration is characterized by a higher cell adhesion power in the upper, and, especially, in the middle epidermis stratum. The cell adhesion power indices in these strata, and cell mitotic activity of basal epidermis stratum near the cicatrix depend on conditions of connective tissue formation in the wound defect. The effect of physiological solution and trypsin on the wound process results in a moderate rising of intercellular contact strength and in decreasing in the number of dividing basal stratum cells, while addition of ronidase solution results in a sharp rising of the corneous scale adhesion strength, and in establishing the straight correlation between this index and the speed of epidermocyte production. PMID- 1455557 TI - [Molecular biological differences between strains of Mycoplasma gallisepticum]. AB - Differences in virulence of two Mycoplasma gallisepticum strains, S6 and A5969, are confirmed in experiments with chickens. Macromolecular discrepancies detected between these two strains are concerning the genomic size, electrophoretic spectra of DNA and proteins. Cross immunoblotting data with polyclonal and monoclonal antibodies reveal major immunogens of protein nature in both the strains. Homologous proteins with different electrophoretic mobility are detected in other four M. gallisepticum strains. A possible participation of these proteins of M. gallisepticum in adhesion to the host cells is discussed. PMID- 1455558 TI - [The reorganization of the extracellular matrix in mixed monolayer cultures]. AB - Heterotypic cells in combined monolayer sheets can push each other from the substratum due to a competition in attachment of pseudopodia of contacting heterotypic cells: different types of epithelium can push each other and fibroblasts from the substratum in mixed cultures. The formation of extracellular matrix in mixed cultures was studied with antisera to fibronectin and laminin by immunofluorescent microscopy. It was shown that one group of cells in the sheet pushed another group together with their extracellular matrices. It is supposed that the interaction of contacting heterotypic cells and associated extracellular matrices may play an important role in distribution of different cell types in embryogenesis and carcinogenesis. PMID- 1455559 TI - [The differential staining of murine metaphase chromosomes in early embryogenesis after treatment with restrictase AluI in situ]. AB - The picture of differential staining of early mouse embryogenesis metaphasic chromosomes, from the first cleavage up to 10 days of gestation, after digestion by restriction endonuclease AluI was studied. It was shown that depending on the degree of digestion by endonuclease differential bandings of G+C- or C-type were observed. After the least digestion only the first cleavage chromosomes were differently stained. A slight difference in intensity of staining between paternal and maternal chromosomes of the zygote was observed. All the mouse chromosomes were identified after AluI digestion and staining after Giemsa. PMID- 1455560 TI - [DNA synthesis and content in human decidual cells at different stages of differentiation based on flow cytometry data]. AB - Flow cytometry analysis of the DNA content of human decidual cells at the physiologically normal pregnancy and in the case of toxicosis was carried out. During the normal pregnancy DNA-histogram parameters were seen to vary: the number of S-phase cells decreased, the coefficient of variation of the G1/0 peak increased. These alterations correlated positively with the increase in the share of decidual cells with properties of terminally differentiated cells. The most pronounced quantitative alterations in variability of DNA content in G1/0 cells were observed in cases of toxicosis of pregnancy. Phenomena of variability of the nuclear DNA in the terminally differentiated decidual cells is considered to be a sign of cell death through apoptosis. PMID- 1455561 TI - [The use of several types of metal cations--a new approach to the study of the metallophilia of Ranvier's nodes of nerve fibers]. AB - Mechanisms of metal affinity of Ranvier's nodes of myelinated nerve fibers in the peripheral nerve system have been investigated. It is indicated that Fe(3+)-ions are able to reduce to Fe(2+)-ions. Ag(+)-ions compete with Fe(3+)-ions for places of adsorption in a gap [correction of chick] between myelinated segments of Ranvier's node. It is demonstrated that Fe(3+)- and Fe(2+)-ions are adsorbed in the gap [correction of chink], while Ag(+)-ions are adsorbed in the gap [correction of chink] and axon in the bulbs of the node. One can increase ferrocyanide of ferrous sediment by several times by ferricyanide of ferrous sediment as well as by ferrocyanide of silver and of metal silver ones. A possibility to use several kinds of metal ions for demonstration of cytochemical heterogeneity of nerve fibre membrane is discussed. PMID- 1455562 TI - [The interrelation between changes in the structural organization of replicon clusters, a retarded fork displacement rate and the high level of spontaneous SCEs in form II of xeroderma pigmentosum]. AB - A cytogenetic observation, that the sister chromatid exchanges (SCE) occur 3 times more frequently in a special form of xeroderma pigmentosum--XPII than in the norm, prompted a study of DNA replication in this rare disease. Using DNA fiber autoradiography, the rate of fork movement and the frequency of initiation in the adjacent clusters of replicons were estimated. The rate of fork movement was significantly slower than that in classical XP and in normal cells. Here evidence was provided on another defect in DNA replication in XPII that involves a significantly decreased number of simultaneously operating adjacent clusters of replicons, which results in a decreased rate of DNA chain-growth. According to the Painter replication model for SCE, the exchanges arise due to double-strand DNA breaks occurring on the border between two adjacent clusters, respectively, completely and partially replicated. A retarded fork-displacement rate together with a decreased rate of DNA-chain growth may cause this situation to persist longer than in the norm. Thus, our data provide a further support of the replication model for SCE. A similar combination of cytogenetic and molecular defects has been obtained earlier in the Bloom syndrome cells. PMID- 1455563 TI - [The effect of opioid peptides on the size of the cellular aggregates in a cell culture of rat embryonic spinal cord]. AB - Effect of opioid peptide Leu-enkephalin (Leu-enk) and synthetic analogue of Leu enk on fetal rat spinal cord cells in culture was studied. Activity of peptides was measured in dissociated culture on aggregation assay. The aggregated place was calculated on days 3 and 6 of culturing, because this parameter indicates the cell adhesion and neuronal and glial survival. The aggregation place was shown to increase due to peptide action: with Leu-enk and dalargin by 1.6 and 1.7, resp., compared to the control; both calculations being made on days 3 and 6 of culturing. The results of the analysis of opioid peptide activity during culturing of dissociated cells of fetal rat spinal cord demonstrate that the peptides changed the adhesion of cells and increased their survival. The results of the present and our earlier experiments suggest that the opioid peptides may be growth factors for CNS cells and may play a role in development and regeneration of the nervous tissue. PMID- 1455564 TI - The gonadotropin-releasing hormone (GnRH) agonist-induced initial rise of bioactive LH and testosterone can be blunted in a dose-dependent manner by GnRH antagonist in the non-human primate. AB - Gonadotropin-releasing hormone (GnRH) agonists induce a clinically undesirable, transitory but very pronounced initial rise of gonadotropin and gonadal steroid secretion. We investigated, in a non-human primate model, whether the initial stimulatory effects of GnRH agonists can be avoided by a short period of pretreatment and simultaneous treatment with a GnRH antagonist. Three groups of five adult male cynomolgus monkeys (Macaca fascicularis) received a single s.c. biodegradable implant loaded with the GnRH agonist, buserelin ([D-Ser(TBu)6 desGly-NH2]-GnRH), releasing approximately 50 micrograms buserelin daily. From 1 week before to 1 week after inception of administration of GnRH agonist, group 1 received the GnRH antagonist vehicle, and groups 2 and 3 were given s.c. injections of the GnRH antagonist Nal-Glu ([Ac-D-Nal(2)1,D-4-Cl-Phe2,D-Pal3,D Arg5,D-Glu6(AA),D- Ala10]-GnRH) at a dose of 450 or 2250 micrograms/kg daily. In the absence of GnRH antagonist, the GnRH agonist induced a marked elevation of serum luteinizing hormone (LH) and testosterone lasting for 2 and 5 days, respectively. In group 2, Nal-Glu reduced basal hormone secretion and delayed the peak of GnRH-agonist-induced hormone secretion by 1 day. In group 3, the GnRH agonist-induced rise of LH and testosterone was prevented in three animals and did not exceed baseline hormone levels in the other two animals. Areas under the LH and testosterone curves were significantly reduced in group 3 compared to group 1. After withdrawal of the GnRH antagonist, a second transient rise of hormone secretion was observed. Except for testosterone in group 2, this rise did not exceed the baseline range of hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455565 TI - Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat. AB - The feasibility of using a vaccine against luteinizing-hormone-releasing factor for suppression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague Dawley rats with a mean basal body weight of 200 g were immunized with anti-LHRH DT (20 micrograms/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility. PMID- 1455566 TI - Oxalate transport in cultured porcine renal epithelial cells. AB - Oxalate-containing kidney stones are the most common type (75%) of renal stones. In order to control oxalate excretion in the urine, a basic understanding of the cellular transport of oxalate is imperative. We have utilized the technique of continuous cell culture to establish and characterize a model system to study renal epithelial cell (LLCPK1) oxalate transport. Our data demonstrate that oxalate uptake in these cells is dependent on time, concentration and energy. The Km for oxalate uptake was 200 microM. Oxalate uptake was decreased at lower temperatures and elevated in an acidic extracellular environment. Both anion exchange inhibitors DIDS and SITS inhibited oxalate uptake. Sulfate, chloride, and bicarbonate decreased oxalate uptake, as did the diuretics bumetanide and furosemide. There was no evidence for the co-transport of oxalate with sodium. Our data show that monolayers of cultured kidney epithelial cells are a valuable model system for study of the basic cellular mechanisms of oxalate transport. PMID- 1455567 TI - Citrate and recurrent idiopathic calcium urolithiasis. A longitudinal pilot study on the metabolic effects of oral potassium sodium citrate administered as short-, medium- and long-term to male stone patients. AB - In male patients with idiopathic recurrent calcium urolithiasis (RCU) the effects of oral potassium sodium citrate (PSC) on acid-base, citrate and mineral metabolism were investigated. There were 17 normocitraturic and 15 hypocitraturic patients. The examination time points in our clinical laboratory were prior to medication and after 3, 6 and over 12 months of medication. Urine collection periods were over 24 h, 2 h--after an overnight fast--3 h postprandially. Acceptance by the patients was poor, a large number refusing to take PSC for 12 months. Compliance of the patients continuing with the study was adequate as assessed by the urinary excretion of potassium and sodium. No unwanted side effects were observed. After 3 months of PSC medication a compensated metabolic alkalosis developed; in the urine calcium was decreased, while citrate, pH and oxalate were increased, as were hydroxyapatite supersaturation and calcium phosphate particles. After more than 12 months of PSC medication, citrate and pH tended toward the pretreatment baseline values, while hydroxyapatite supersaturation and calcium had already returned to pretreatment values. Despite ongoing PSC intake, patients with pre-existing hypocitraturia had lower urinary citrate than patients with previous normocitraturia, while the concomitant pH and hydroxyapatite supersaturation in the urine of the former remained at levels close to those of the latter. Under the influence of PSC, parathyroid gland function remained unchanged, but serum levels of bone alkaline phosphatase and osteocalcin were low, and urinary hydroxyproline was high.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455568 TI - Impact of voltage and capacity on the electrical and acoustic output of intracorporeal electrohydraulic lithotripsy. AB - The electrical and acoustic output created by the spark discharge for electrohydraulic lithotripsy at the tip of a 3.3-F probe was evaluated. Spark generation was achieved by variable combinations of voltage and capacity. The effective electrical output was determined by means of a high-voltage probe, a current coil and a digital oscilloscope. Peak pressures, rise times and pulse width of the shock waves were recorded using a polyvinylidene difluoride needle hydrophone in 0.9% NaCl solution at a distance of 10 mm. The effective electrical output is lower than the calculated output, due to inductivities, capacities and resistances of the cables and plugs. The life of the probes is markedly shorter when a combination of high voltage and low capacity is used than with low voltage and high capacity corresponding to the same energy. The peak pressure and the slope of the shock front depend solely on the voltage, while the pulse width is correlated with the capacity. The pulse intensity integral of the shock wave is likely to be the best equivalent to the applied energy. PMID- 1455569 TI - Periurethral colonization and urinary leukocytes as markers for bacteriuria in children with neurogenic bladder. AB - Bacteriuria and associated renal damage is common in children with a neurogenic bladder, but the pathogenesis of urinary tract infection (UTI) is undefined. We examined the association between periurethral bacterial colonization and the presence of urinary leukocytes in 76 catheter urine specimens from children with neurogenic bladders. Although all the children were asymptomatic, 38/76 (50%) of the urine cultures were positive. Periurethral colonization was significantly more common with positive than with negative urine cultures, suggesting a pathogenetic role for periurethral bacteria in infection of the neurogenic bladder. Urinary leukocytes were present in 24/38 (63%) with positive cultures, as against none (0/38) of those with negative urine cultures, and their presence represents a host response to bladder bacteriuria. PMID- 1455570 TI - New device for penile vibrotactile stimulation: description and preliminary results. AB - A small, lightweight mini-vibrator for measuring penile sensitivity is described. Data on subjective thresholds to vibrotactile stimulation were collected from sexually functional and dysfunctional men during both flaccid and tumescent penile states. Two sites, the dorsal and ventral surfaces of the glans penis, were stimulated. Results indicated a significant correlation between thresholds obtained with the mini-vibrator and those obtained with another stimulating device. In addition, the patterns of sensitivity in the flaccid and in the tumescent penis were similar to those found in previously studied samples of sexually functional and dysfunctional men. This device has advantages over other vibrators in that it can be attached directly to the penis and does not lose contact with the penile surface during tumescence. PMID- 1455571 TI - Karyometry in recurrent superficial transitional cell tumors of the bladder. AB - Transitional cell carcinoma of the bladder has a high recurrence rate after local treatment. Progression to a higher stage occurs in 10-30% of the recurrent tumors, and early detection of potentially progressive tumors is important. In the current study morphometric, densitometric, and chromatin textural features of nuclei of superficial bladder tumors (pTa-T1) were studied to determine the value of karyometric features in the prediction of tumor progression. Seventy-two histological samples from 36 patients, consisting of both the primary and the first recurrent superficial tumor, were analyzed. Patients were divided into two groups: those with tumor progression, defined as an increase in tumor stage or occurrence of metastatic disease, and those without. Discriminant analysis on four karyometric features resulted in correct prediction of prognosis of 78% and 97% in the primary and recurrent tumors, respectively (P < 0.001). Tumor grade and stage did not offer additional information concerning prognosis. Karyometric analysis of recurrent superficial transitional cell tumors can be useful in selecting patients who need a more aggressive therapy. However, tumor characteristics of recurrent tumors varied and continuous evaluation of the karyometric features is necessary for early detection of an increase in the malignant potential of the tumor. PMID- 1455572 TI - Anatomy of the mouth and teeth of the cat. AB - Anatomy of the feline mouth is described. Dental occlusion and tooth and periodontal structure are reviewed. Also included is a thorough discussion of dental terminology. PMID- 1455573 TI - Feline oral-dental radiographic examination and interpretation. AB - This article describes the technique of taking intraoral radiographs and developing film. Interpretation of oral radiographs is described. Radiation safety is reviewed. A troubleshooting section is included. PMID- 1455574 TI - Oral-dental disease in cats. A feline practitioner's perspective. AB - The impact and relevance of dentistry in a general feline practice is detailed. Hospital policy and protocol are described for client education, preanesthetic evaluation, dental procedures, and recall programs. A discussion of commonly observed feline dental problems is included. PMID- 1455575 TI - Feline experimental models for control of periodontal disease. AB - Feline periodontal disease has many elements in common with human and canine disease. Anatomic, physiologic, microbiologic, and immunologic differences between the three species make it impossible to predict with certainty whether successful approaches to controlling and treating canine oral disease will also prove successful in cats. We have developed methods for reproducible, quantitative evaluation of feline dental plaque and calculus. Our studies demonstrated that feline plaque accumulation peaks at 1 week after prophylaxis and that calculus peaks at 4 weeks after prophylaxis. These methods should be adequately sensitive to document control of plaque and calculus accumulation by efficacious chemical or antimicrobial agents. PMID- 1455576 TI - Inflammatory oral cavity diseases of the cat. AB - There is a great deal of frustration among veterinarians about the diagnosis and treatment of inflammatory diseases of the oral cavity of the cat. This frustration is due to both the high frequency of feline oral inflammatory lesions and our poor understanding of their causes. This poor understanding can be blamed on several things: (1) a rapidly emerging, but still relatively poor, understanding of feline diseases in general and nutrition in particular; (2) a tendency to lump rather than separate specific oral inflammations; (3) a tendency not to use a thorough and systematic approach to diagnosing oral cavity disease; and (4) the reluctance of veterinarians to apply what is already known about human oral cavity diseases to cats. When problems 2 through 4 are adequately addressed, it becomes apparent that we really know more about oral cavity disease in the cat than we thought we knew and that great progress has been made. The task ahead is to define, in precise medical terms, those remaining disease entities of the oral cavity that pose the greatest health risk to cats, to apply what has been already been discovered from human disease counterparts, and to study them systematically. PMID- 1455577 TI - Gingivitis/stomatitis in cats. AB - Any alteration in the balance of bacterial challenge versus the host's ability to resist and repair will result in oral lesions that are similar in appearance. The bacterial cause of gingivitis and periodontitis in humans and in all other animals in which it has been studied is firmly established, and specific species of predominantly gram-negative anaerobes have been implicated. Naturally occurring or acquired immunopathologies are likely to result in premature dental disease. When oral disease is associated with the accumulation of plaque, a positive response can be achieved by reducing the bacterial challenge to the host through the maintenance of oral hygiene by timely professional dental prophylaxis and home care. Disease that is the result of atypical immune responses, however, can be much more difficult to manage. Such oral disease can occur with either immune deficiencies or exaggerated immune responses, and it is likely that multiple mechanisms are active concurrently. In any case, gram-negative anaerobes present in plaque are likely to be a major contributing factor. Therefore patients with chronic refractory gingivitis-stomatitis must be considered to be plaque intolerant. Only with a frequent regimen of aggressive and thorough professional dental treatment plus meticulous oral home care on a daily basis can one expect to keep these cases in remission. Because this is often unrealistic, the only other way to keep these patients free of disease is by total dental extraction. The tissues that are colonized by the causative organisms must be eliminated. All root tips and bony sequestra must be removed and healing with intact epithelium accomplished before these cases will go into remission. Edentulous feline patients that continue to have signs of gingivostomatitis have been found to have an area of nonhealed bony sequestrum and chronic osteomyelitis. Once effective debridement has been accomplished and epithelial healing completed, nonresponsive cases can be expected to go into remission (Color Plate 2, Figure 7). It is hoped that as more is learned about this frustrating problem, the many factors influencing feline oral disease will be scientifically documented. In the future, actual diagnoses can be systematically made early on in disease, and treatment will be more than just symptomatic. PMID- 1455578 TI - Etiopathogenesis of feline dental resorptive lesions. AB - There are several factors in the etiopathology of feline resorptive lesions. They may be considered as local immune-response mediating cell and humoral factors; release of biochemical components in dental and paradental tissues to attract odontoclasts; mechanical stress, including occlusal mechanism; and local and systemic calcium regulation, including remodeling of mineralized tissue and dietary intake of calcium. PMID- 1455579 TI - Feline dental resorptive lesions. Prevalence patterns. AB - Surveys were carried out in cats presented for dental examination in the Netherlands (432 cats) and in the United States (78 cats). In 62% of the Dutch cats and 67% of the US cats, resorptive lesions were present. In the Dutch study, Asian Short-hair (principally Siamese) cats were most commonly involved, and male cats were more commonly affected than females. The most commonly affected teeth were the fourth maxillary premolar and the mandibular premolar and molar teeth. PMID- 1455580 TI - Subgingival odontoclastic resorptive lesions. Classification, treatment, and results in 58 cats. AB - A commonly recognized dental problem in cats is the resorption of tooth structure and subsequent loss of the tooth. These tooth defects are often very painful, because the sensitive dentin layer is exposed. The destruction of the tooth through odontoclastic resorption is considered a consequence of inflammatory resorption, probably secondary to periodontal inflammation. Because these resorptive lesions are progressive in nature, it is best to stage this progression of resorption in order to address treatment planning. The purpose of this study was to evaluate a group of 58 cats with resorptive lesions to determine the outcome of treatment 6 months or longer after restoration. In 81% of the cats, there was loss of the tooth, evidence of further resorption, or loss of the restoration at one or more resorption sites. Of the 154 teeth restored, only 33% showed no further evidence of loss of tooth structure. PMID- 1455581 TI - Feline endodontics. AB - One misconception in veterinary medicine is that fractured teeth do not need to be treated, or treatment should consist of extraction only. Two common causes of endodontic disease in the cat are fractures and secondary to cervical line lesions. Endodontic technique can be useful in returning a diseased tooth to normal, pain-free function. Conventional endodontics can be used to treat fractured canine teeth or partially destroyed molars. Surgical endodontics is useful in cases in which an apical seal cannot be established by conventional methods. Pulp capping can preserve a vital tooth as an alternative to extraction. PMID- 1455582 TI - Feline malocclusion. AB - Modern feline malocclusion is the result of altered dento-facial proportions from the normal occlusion. The development of the brachycephalic and dolichocephalic head types has resulted in displaced dentition with accompanying soft-tissue trauma. PMID- 1455583 TI - Treatment of jaw fractures in small animals with parapulpar pin composite bridges. AB - This article describes a 5-year study of 73 cats that were surgically treated for mandibular fractures or combinations of fractures with luxation of the temporomandibular joint. Surgical technique and results are described in detail. PMID- 1455584 TI - Infection of laying hens with Salmonella enteritidis PT4 by conjunctival challenge. AB - The direct administration of either 103 or 108 cells of Salmonella enteritidis phage type 4 on to the conjunctiva of laying hens resulted in systemic infection. The bacterium was isolated from a variety of tissues, including the ovary and oviduct, and it was excreted in faeces for at least 27 days after infection. PMID- 1455585 TI - Generalised tuberculosis with orchitis in the bull. PMID- 1455586 TI - Evaluation of the complex trapping blocking-ELISA in a serological survey during the Belgian classical swine fever epizootic in 1990. PMID- 1455587 TI - Docking of dogs. PMID- 1455588 TI - Effect of professional status on career path. PMID- 1455589 TI - Swine vesicular disease in the European Community. PMID- 1455590 TI - Use of ivermectin as a treatment for sheep scab. PMID- 1455591 TI - Biological hazards in the workplace. PMID- 1455592 TI - Spongiform encephalopathy in a captive puma (Felis concolor). AB - A captive adult puma developed ataxia, a hypermetric gait and whole body tremor. The signs progressed over a period of six weeks. Histopathological examination following euthanasia demonstrated spongiform encephalopathy, gliosis and mild non suppurative meningoencephalitis. Immunostaining with a polyclonal antiserum revealed prion protein (PrP) associated with these changes in sections of cervical spinal cord and medulla. This is the first confirmed case of a scrapie like spongiform encephalopathy described in a non-domestic cat in the United Kingdom. PMID- 1455593 TI - Duration of urinary excretion of leptospires by cattle naturally or experimentally infected with Leptospira interrogans serovar hardjo. AB - The excretion of Leptospira interrogans serovar hardjo in the urine of cattle was studied in naturally and experimentally infected animals. Five of 15 naturally infected animals with microscopic agglutination test titres of > or = 1:300 shed leptospires for between 28 and 40 weeks. Twenty yearling heifers, experimentally infected by either the supraconjunctival or intrauterine routes, shed leptospires for from eight to 60 weeks; the 10 infected via the uterus shed L interrogans serovar hardjo for a mean of 26 weeks (range eight to 54 weeks) and the 10 infected by the supraconjunctival route shed the organism for a mean of 32 weeks (range 12 to 60 weeks). The results suggest that natural infection results in more prolonged excretion than experimental infection. No intermittent or seasonal excretion of the organism was observed. After the initial experimental infection, large numbers of leptospires were shed in the urine for several weeks, and thereafter there was a progressive decline in the number of organisms shed. PMID- 1455594 TI - Mortalities and wasting in Indonesian sheep associated with the trematode Eurytrema pancreaticum. PMID- 1455595 TI - Demonstration of Isospora suis oocysts in faecal samples. PMID- 1455596 TI - Welfare of animals at markets. PMID- 1455597 TI - Docking of dogs. PMID- 1455598 TI - Disease risks in the European community. PMID- 1455599 TI - Sitting of transponders. PMID- 1455601 TI - Influence of atropine on the acute toxicity of isometamidium. AB - The effectiveness of atropine in blocking the acute toxic effects of the antitrypanosomal drug isometamidium (ISMM) was evaluated in mice and goats using lethality as the primary index. The median lethal dose (LD50) of ISMM in nonatropinized mice was 45.3 mg/kg bodyweight (SE +/- 5.3 mg/kg bodyweight), whereas the LD50 of ISMM in mice pre-treated with atropine was 71.7 mg/kg bodyweight (SE +/- 13.2 mg/kg bodyweight). The increase in LD50 was about 60%. The ratio of the slope of the dose-response curve for ISMM in non-atropinized mice to that in atropinized mice was about 4:1. The results showed that atropine was effective in considerably reducing the lethal effect of ISMM in mice. In contrast, experiments in goats showed markedly different results; atropine was not effective in reducing the lethality of ISMM. It was concluded that in mice atropine has some beneficial action in cases of overdosage or poisoning by ISMM. Treatment with atropine should be attempted as an antidotal measure in humans accidentally poisoned with ISMM. PMID- 1455600 TI - An analytical study of antibacterial residues in meat: the simultaneous determination of 23 antibiotics and 13 drugs using gas chromatography. AB - Simultaneous determination of 7 penicillins, 3 tetracyclines, 5 aminoglycoside antibiotics, 5 macrolide antibiotics, 2 polyether antibiotics, chloramphenicol and 13 drugs was evaluated. The 36 agents in meat were extracted with 10% trichloroacetic acid. The extracted solutions were adsorbed on an Amberlite XAD-2 resin column and an activated carbon resin column and then eluted with methanol and 0.01N HCl-methanol, respectively. The eluted solutions were concentrated to dryness and trimethylsilylated with pyridine, N, 0-bis (trimethylsilyl) acetamide, N-trimethylsilylimidazole and trimethylchlorosilane. They were then measured by gas chromatography with a flame-ionization detector. The recovery for almost all of the 36 compounds from the original meat specimens was more than 82%. The limits of detection for most of the 36 agents using this method were equivalent to the original individual methods of analysis. PMID- 1455602 TI - The relationships between neuronal activity and behavioral seizures induced by Palicourea marcgravii in rats. AB - To characterize the convulsions induced by an aqueous extract of Palicourea marcgravii (Pm), male Wistar rats were injected sc with 3.75 g/kg of the extract, and electroencephalogram and behavior were observed for periods up to 180 min after the Pm injections. Sleep spindles and generalized convulsive seizures were observed following Pm administration. Spiking activity was detected in both cortical and hippocampus recordings. They lasted approximately 2 min and were followed by a period of postical depression and/or death. These results agreed with previous behavioral experiments which suggested the toxic effect of Pm aqueous extract was mainly at the central nervous system level. PMID- 1455603 TI - Epidemiology of children poisoning: comparison between telephone inquiries and emergency room visits. AB - We studied 674 telephone inquiries to the Poison Information Centre and 532 Emergency Room (ER) visits due to suspected poisonings in 1018 children below the age of 16 y and living at Trieste. The cases were prospectively recorded during 1985-1989. Age distribution, toxic substances and consequences were different in the 2 groups. Telephone inquiries concerned children below the age of 5 y more frequently, and most of the exposures were assessed as non-toxic. Among children admitted to the hospital ER, 22.2% were more than 10-y old, and of these 79.7% were confirmed poisonings. This study demonstrated the need to take account of both Poison Control Centre and ER data to get reliable information on the occurrence of poisonings in children. PMID- 1455604 TI - Dermal exposure to detergents. AB - Epidermal erosion and a 40-60% increase in histamine content of skin were observed in guinea pigs treated with different concentrations of detergents. The primary irritation indices of these animals ranged between 0.3 and 1.5. Eight human subjects with skin lesions attributable to detergent exposure were patch tested with 500 mg of detergents. A positive reaction was observed in 7 of 8 cases. In 4 cases reaction was observed within 24-48 h, while 3 cases had a severe reaction after 72 h. IgA and IgM levels were raised in 2 subjects. This study highlights the irritancy potential and toxic effects of detergent products available in Indian markets. PMID- 1455605 TI - Teratogenic effects of methyl parathion in developing chick embryos. AB - The effect of methyl parathion (MP) on developing chick embryos was investigated. The embryos were exposed at different stages of development to various doses of MP via the yolk sac route. This resulted in retarded growth which included reduced body weight and reduced body length and length of leg bones. Other teratogenic signs observed were short neck, muscular hypoplasia of legs, abdominal hernias and haemorrhagic spots in brain and upper body. These findings suggest that MP was a teratogen when injected into the yolk sacs of developing embryos. PMID- 1455606 TI - Subchronic toxicity studies of fenbendazole in rats. AB - The effects of prolonged exposure of rats to fenbendazole were investigated. Fenbendazole was given daily by gavage for 14 consecutive days. These dosages (3000, 500 or 50 mg/kg/d) produced reductions in body weight gains. Renal tubular hyperemia or hemorrhage and glomerular capsule dilation, increased serum creatinine and hepatocellular granular degeneration occurred at dosages of 500 and 3000 mg/kg/d. Renal tubular epithelial cell granular degeneration and tubular dilation, increased serum glutamic pyruvic transaminase, cardiac hemorrhage and granular degeneration also occurred at 3000 mg/kg/d. PMID- 1455607 TI - In vitro/in vivo effects of 7,8-benzoflavone on aryl hydrocarbon hydroxylase activity of mice. AB - The activity of aryl hydrocarbon hydroxylase (AHH) in mouse liver microsomes was assayed in vitro in the presence of 7,8-benzoflavone (7,8-BF). The mice had been previously treated with the AHH inducer 3-methylcholanthrene (MC), 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) or vehicle (olive oil) alone. The effects of 7,8-BF on the AHH activity were markedly different according to the genetic responsiveness of the mice towards aromatic hydrocarbons (Ah). 7,8-BF had either an inhibitory or an enhancing effect on AHH, depending on the Ah responsiveness and previous treatment with MC or TCDD. In contrast, a single administration of 7,8-BF induced microsomal AHH, but the effect was much lower than MC or TCDD in both strains of mice. Simultaneous treatment or pre-treatment with 7,8-BF produced an inhibitory effect on AHH induction by MC or TCDD. Post-treatment with 7,8-BF inclined to promote the induction of AHH by MC or TCDD. These results suggest that the inhibitory effect of 7,8-BF is more exaggerated in vitro than in vivo. Inhibitory effects would be limited to AHH induction from MC or TCDD in in vitro studies, while they would depend on the time of application or Ah responsiveness in studies in vitro. PMID- 1455609 TI - Sudden death in ten psittacine birds associated with the operation of a self cleaning oven. AB - Psittacine birds can develop severe and often fatal pneumonitis when exposed to various noxious inhalants. Toxicosis in these birds caused by inhalation of pyrolysis products produced from overheated polytetrafluoroethylene-coated cooking pans on stove tops is well known, but compounds emitted from burned foods and other materials can also be toxic. We present a case of fatal pneumonitis in 10 psittacine birds associated with the operation of an oven in the self-cleaning mode. PMID- 1455608 TI - Reversal of ethanol-induced respiratory depression by flumazenil. AB - Flumazenil is effective in reversing sedation resulting from benzodiazepine (BZD) toxicity. Its use for other causes of sedation have not been well described. A 23 y-old male was found unconscious. Upon being aroused, the patient stated he had recently ingested 1 1/2 bottles of vodka/beer and 250 mg of diazepam. Physical examination revealed shallow breathing and respiratory depression. Arterial blood gases were consistent with the clinical diagnosis of respiratory depression (pH 7.34, pCO2 47, pO2 99). However, after receiving 3 mg of flumazenil, the respiratory depression improved so that the patient no longer required intubation. The drug screen returned negative for BZDs and the patient had a blood alcohol level of 332 mg/dl. He later denied BZD use. The patient's clinical course improved throughout the study period, and mechanical ventilation was avoided. This report reflects a possible role for flumazenil in reversing the respiratory depression produced by ethanol ingestion. PMID- 1455611 TI - Chemical hepatitis associated with occupational exposure to halothane in a research laboratory. AB - We report a case of clinical hepatitis associated with occupational exposure to halothane in a research laboratory. A biochemist who for 3 y repeatedly used halothane for sedation and euthanization of rats suffered recurrent episodes of epigastric discomfort, culminating in an episode of malaise, anorexia, jaundice and elevated liver associated enzymes that promptly resolved after removal from exposure to halothane. Serologic testing for viral sources and risk factors for non-infectious hepatitis were negative. Halothane-induced hepatitis has been documented as an idiosyncratic reaction among anesthetized patients and has been reported once in operating room personnel. The mechanism for halothane-induced hepatitis is proposed to be a hypersensitivity reaction to liver neo-antigens produced by the halothane metabolite 2-chloro-1, 1, 1-trifluoroethane. PMID- 1455610 TI - Simazine toxicosis in sheep. AB - A case of simazine toxicosis in sheep was investigated. Affected animals exhibited generalized muscle tremors which progressed to mild tetany followed by collapse of the hind legs. Other signs included a short prancing gait with head tucked in a similar manner to that of a show pony. Death occurred within 2 to 3 d of the appearance of clinical signs. Mild to acute myocardial degeneration was evident; the livers had mild to acute hepatic fatty change. The levels of simazine found in livers varied from less than 0.2 mg/kg to almost 2 mg/kg in the worst affected animals. PMID- 1455612 TI - Orthotopic liver transplants necessitated by acetaminophen-induced hepatotoxicity. AB - BACKGROUND: Acetaminophen-induced hepatotoxicity has been recognized since 1966. Patients experiencing a massive hepatic insult due to acetaminophen (APAP) may recover with minimal residual complications or develop fulminant hepatic necrosis. We report 3 patients with hepatic failure due to an APAP overdose who received orthotopic liver transplants and survived. CASE REPORTS: An 18-y-o female ingested 60 500 mg APAP tablets (30 g). She presented with tachycardia and lethargy stating that she had taken amoxipine, carbamazepine, and lorazepam. She began to recover but on day 2 experienced an upper gastrointestinal bleed and became hypotensive and hyperpyrexic. She developed hepatic encephalopathy and it was then determined she had ingested APAP. Her APAP level was 13 micrograms/ml 96 h post-ingestion. She was successfully transplanted 19 d post-ingestion with recovery. A 40-y-o female was admitted for flu-like symptoms persisting for 7 d. She was jaundiced, hyperventilating and hypotensive. She admitted ingesting approximately 17 g APAP over 36 h. Her APAP level was 12.2 micrograms/ml. Her condition worsened and on day 3 she was in grade IV coma. She was successfully transplanted 4 d post-arrival with recovery. A 16-y-o female ingested an unknown amount of APAP. She presented approximately 24 h post-ingestion with a serum APAP level of 130 micrograms/ml. Her condition deteriorated and she became encephalopathic with grade IV coma. She was successfully transplanted on day 7 post-arrival. DISCUSSION: Hepatotoxicity can occur as a result of either acute or chronic APAP overdose. Although n-acetylcysteine (NAC) is effective antidotal therapy, it must be used within 8-12 h post-ingestion to be optimally effective. Inaccurate patient histories may prevent NAC administration resulting in hepatotoxicity. CONCLUSION: Liver transplantation is a viable option to be considered in those APAP overdose patients who experience rapidly progressing encephalopathy, hemolysis, and hepato-renal failure. PMID- 1455613 TI - A literature review of dermatotoxicity. AB - Dermatotoxicity is the skin's response to chemical substances that produce damage. Penetration of the chemical to the various skin layers is important and may result in irritation, allergic contact dermatitis, contact urticaria, one of various forms of photosensitization, or other cutaneous reactions. The testing of new products or industrial chemicals for potential dermatotoxicity is an important process in protecting the public's health. PMID- 1455615 TI - Evaluation of a computerized program (ARSENIC) as an aid for telephone consultations in a poison center. AB - ARSENIC is a computerized system providing assistance for telephone consultation in poison centers. Its main characteristic is to blend the document consultation process with the case-recording procedure. It has been used in the daily routine of our poison center since 1987. To evaluate this system, 2 weeks were randomly chosen. During one, ARSENIC was used by the telephone responders; during the other week, traditional paper documents and files were used. Document search times, coding times and quality of responders were recorded by a blinded observer and analysed in total and on the basis of the training of the telephone officer (medical student, resident or toxicologist). ARSENIC decreased the document search times (3.1 +/- 2.7 min vs 3.8 +/- 2.9 min; p less than 0.05) and did not increase coding time (2.1 +/- 1.2 min vs 2.2 +/- 1.4 min; NS). For each group of telephone responders, answer quality increased with ARSENIC. More important, the answer quality of less-trained officers using ARSENIC was similar to that of trained toxicologists without ARSENIC. The quality assurance given by ARSENIC was, for us, the most important argument for computer use at telephone desks. PMID- 1455614 TI - Immunotoxicity in the bovine animal: a review. AB - The immune system is a complex biological system involving cellular defenses as well as endogenous and exogenous factors. The potential for immune system exposure to immunotoxins in the environment is well documented. However, caution should be exercised when extrapolating meaningful conclusions from experimental data to assess risk factors to the bovine. Mycotoxins alter immune-mediated activities in cattle and are major immunotoxic risks. Another risk to the bovine is lead. Poor disposal of pollutants in the environment enhances this risk factor. One of the most controllable risk factors is the administration of immunotoxic drugs and biologics. Most of these compounds have minimal immunotoxic activity at recommended dosages. The extra-label use of drugs resulting in super therapeutic concentrations has increased the probability that certain drugs may act immunotoxicologically. PMID- 1455616 TI - A ten-step quality assurance program for regional poison information centers. AB - BACKGROUND: Our regional poison information center (RPIC) has developed and implemented an ongoing quality assurance (QA) initiative, using performance indicators and evaluation thresholds to permit a planned and systematic process for monitoring the quality, appropriateness and effectiveness of service. METHODS: A 10-step QA plan was designed that included delineating the scope of care, identifying the most important aspects of care, identifying indicators and thresholds to monitor performance and outcomes, and establishing a formal medical audit review process to resolve questions and/or problems. RESULTS: This QA program has resulted in verification of the validity of the RPIC's data and services. Threshold indicators (the incidence of accidental poisoning in children less than 6 y, incidence of intentional poisoning among children less than 18 y, appropriateness of home versus hospital management, and reduction in major/mortal outcomes in children less than 6 y) have all been successfully met during the past 12 mo. A medical audit committee objectively reviews and meets to discuss all unique poison exposures or those suffering major/mortal outcomes. Examples of identified problems include the lack of utilizing standard abbreviations during documentation and the need to standardize indications for consulting medical back up. DISCUSSION: RPICs are innovative health services with unique and increasing responsibilities and liabilities. A QA program, designed to objectively and systematically monitor and evaluate the quality and appropriateness of care rendered the poisoned patient, can improve care and resolve identified problems in a timely manner. CONCLUSIONS: A formalized QA program is essential for all RPICs. PMID- 1455617 TI - The OPQ: a proposed instrument for predicting poisoning accident recurrence in young children. AB - A 26-item self-report questionnaire for parents/guardians was constructed for potential use with first-exposure childhood poisoning victims to predict high risk for subsequent poisoning episodes. Data were obtained from 185 subjects served by 1 of 5 US regional poison control centers. The resulting device was labeled the OPQ. Its retrospective validity (R = 0.71) and test-retest reliability (0.81) are viewed as sufficient. The test itself, with accompanying scoring key and norms, are provided here in the hope that other clinicians and researchers will join in subjecting the OPQ to prospective validity studies and other forms of Scale refinement. PMID- 1455618 TI - Clinical signs and mechanism of supermethrin intoxication in sheep. AB - Three Slovak Merino sheep, weighing 38, 40 and 41 kg, were given single doses of 1500, 2700 or 3000 mg supermethrin/kg body weight. Clinical signs of intoxication were observed, and after death or sacrifice free cyanide levels were determined in the rumen contents and liver. The sheep that received 3000 mg supermethrin/kg had 7.2 and 0.58 mg cyanide/kg in the rumen contents and liver, respectively; the sheep that received 2700 mg supermethrin/kg had 5.8 and 0.52 mg cyanide/kg in the rumen contents and liver, respectively; whereas the sheep given 1500 mg supermethrin/kg had no free cyanide detected in the rumen contents or liver. PMID- 1455619 TI - Suspected cases of bromocyclen poisoning. AB - This report summarizes the case histories and tabulates the analytical results from investigations of 8 incidents of suspected bromocyclen poisoning. Interpretation of the results and withdrawal of ALUGAN from the UK market are discussed. PMID- 1455620 TI - Possible larkspur intoxications responsible for acute deaths in cattle. PMID- 1455621 TI - How fast to ticks crawl? PMID- 1455622 TI - Ultrasonic and subsonic pest control devices. PMID- 1455623 TI - Isolation of Fukuoka virus, a member of the Kern Canyon serogroup viruses of the family Rhabdoviridae, from cattle. AB - Four virus strains with identical antigenic properties were isolated from blood samples of 4 sentinel calves having a fever and leukopenea in cultures of HmLu-1 cells derived from baby hamster lung. The virus was identified as Fukuoka virus, classified as a member of the Kern Canyon serogroup viruses of the family Rhabdoviridae, on the basis of its antigenic properties. PMID- 1455624 TI - Detection of mammalian and avian hepadnaviruses by the polymerase chain reaction. AB - The hepadnavirus family contains a number of related viruses able to infect a variety of animal species. In the present study, we have used the polymerase chain reaction and oligonucleotide primers to a conserved region of the viral replicase gene of hepadnaviruses to identify viral sequences in de novo tissues in three well-characterized hepadnavirus systems: the woodchuck, ground squirrel and Pekin duck. We did not detect related hepadnavirus sequences in liver specimens from tree squirrels putatively infected with the tree squirrel hepatitis virus, or in liver specimens from horses with hepatitis (serum sickness), or from dogs with chronic active hepatitis or hepatocellular carcinoma. PMID- 1455625 TI - Immunoblotting study of the antigenic relationships among eight serogroups of Leptospira. AB - Seven strains of Leptospira interrogans belonging to seven different serogroups, and one strain of Leptospira biflexa were analysed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with gradient gels and immunoblotting with hyperimmune rabbit sera raised against each strain. The molecular masses of the proteins were calculated with a polynomial regression model. The SDS-PAGE patterns of the L. interrogans strains were similar and characterized by 24 common bands. This profile was not found for L. biflexa. The immunoblots obtained either with the seven anti-L. interrogans sera or the anti L. biflexa serum allowed a clear distinction between the two species. Taken as a whole, the L. interrogans strain patterns revealed by the seven anti-L. interrogans sera were similar, sharing eight common major bands. A serovar- or serogroup-specific antigenic zone, ranging from 21 to 26 kDa, was also identified. PMID- 1455626 TI - Immunodominant antigens of zoospores from ovine isolates of Dermatophilus congolensis. AB - Zoospores of Dermatophilus congolensis were analysed by SDS-PAGE and western blotting. The electrophoretic profiles of zoospores from 13 isolates of D. congolensis were similar but not identical when stained with Coomassie blue or silver. Immunodominant polypeptides with apparent molecular masses of 76 and 31 kDa were identified in western blots of 13 of 13 and 12 of 13 isolates respectively of D. congolensis reacted with hyperimmune, ovine, antizoospore sera. Identical immunodominant polypeptides were observed in western blots reacted with sera obtained from naturally infected sheep. Initial characterisation of the 76 and 31 kDa polypeptides indicated that they were probably surface exposed because (i) antibodies eluted from the surface of live zoospores after adsorption of hyperimmune antizoospore serum, reacted principally against the 76 and 31 kDa subunit polypeptides in western blots, (ii) adsorption of hyperimmune antizoospore serum with live zoospores resulted in significant diminution of reactivity against both the 76 and 31 kDa polypeptides in western blots, (iii) indirect fluorescent immunostaining of zoospores with antiserum prepared against gel-purified 76 kDa polypeptide, resulted in intense staining of the zoospore outer coat. Immuno-gold electron microscopy of negatively stained zoospores with antiserum prepared against gel-purified 31 kDa polypeptide identified this antigen as a flagella subunit. PMID- 1455627 TI - Sequence analysis of the ROB-1 beta-lactamase gene from Actinobacillus pleuropneumoniae. AB - The ROB-1 beta-lactamase gene from Actinobacillus pleuropneumoniae was cloned and sequenced. The structural gene encodes a 305 amino acid polypeptide. The ROB-1 beta-lactamase gene sequence is identical to that derived from Pasteurella haemolytica and only one amino acid different from that of Haemophilus influenzae, suggesting that they are derived from the same ancestor, and transformed from one to another. PMID- 1455628 TI - Aggregation of bovine platelets by Fusobacterium necrophorum. AB - Washed cell suspensions of biovar A strains of Fusobacterium necrophorum aggregated cattle platelets, but similar suspensions of biovar B strains did not. Platelets were also aggregated by heat-treated bacterial cells or the lipopolysaccharide of biovar A. No platelet aggregation occurred in the presence of the cell-free culture supernatant of biovar A and of all samples prepared from biovar B. Scanning electron microscopy revealed that aggregated platelets were not damaged. Platelet aggregation was inhibited by EDTA, aspirin and quinacrine, and lag time was retarded by these inhibitors, indicating the reaction was a Ca(2+)-dependent, cyclo-oxygenase sensitive event. Platelet aggregation may be a virulence marker, probably mediated by the lipopolysaccharide of F. necrophorum biovar A strains. PMID- 1455629 TI - Molecular cloning and characterization of Mycobacterium paratuberculosis promoters in Escherichia coli. AB - DNA fragments from Mycobacterium paratuberculosis were cloned in the promoter probe plasmid pKO1. Of 957 recombinant DNA clones, 24 induced synthesis of galactokinase (the reporter gene) when these plasmids were transformed into an Escherichia coli strain deficient for the enzyme. A DNA insert from one putative promoter-containing plasmid, designated pAG5, was sequenced and shown to contain, a characteristic RNA polymerase binding site, a probable ribosomal binding site and a putative open reading frame. PMID- 1455630 TI - In vitro stimulation of antibody production to Mycoplasma hyopneumoniae by porcine peripheral blood mononuclear cells. AB - A method to stimulate and detect the in vitro production of antibodies to Mycoplasma hyopneumoniae by porcine peripheral blood mononuclear cells (PBMC) was established. PBMC were cultured in microtiter plates coated with a sonicated M. hyopneumoniae whole cell antigen and the amount of antibody bound to the coating antigen was determined by an enzyme linked immunosorbent assay (ELISA). In addition, the amount of non-bound antibody was determined by testing the culture supernatants in the ELISA which detects porcine antibodies to M. hyopneumoniae. The production of antibodies, in terms of total absorbance values, was enhanced by including 2.5 ng pokeweed mitogen (PWM) per ml growth medium without altering the specificity of the assay. In a pilot experiment, the applicability of the method to follow the development of antigen-reactive cells during primary and secondary immunizations with M. hyopneumoniae was evaluated. Antigen-reactive cells, identified by their ability to produce antibodies to M. hyopneumoniae in vitro, were detected seven days after the primary immunization and reached their highest antigen reactivity one week later. In comparison, antigen-reactive cells could be detected three days after the booster immunization and remained in the circulation for 2 weeks. PMID- 1455631 TI - Application of dot immunobinding on membrane filtration (MF dot) to the study of relationships within "M. mycoides cluster" and within "glucose and arginine negative cluster" of ruminant mycoplasmas. AB - A total of 189 isolates from cattle, sheep and goats, allocated to two groups on biochemical grounds, have been examined by a dot immunobinding membrane filtration (MF dot) method. Seventy glucose fermenting isolates, showing relationships with the "Mycoplasma mycoides cluster", have been compared by MF dot against polyclonal hyperimmunesera prepared against the following reference strains: M. mycoides subsp. mycoides, small colony type (SC), strain PG1 and large colony type (LC) strain Y Goat; M. capricolum strain California Kid (CK); M. species bovine serogroup 7 strain PG50, and, ovine/caprine serogroup 11 strain 2-D. The isolates fell into 5 main groups: (a) 14 serologically homogeneous isolates similar to subsp. mycoides SC PG1 (b) 4 homogeneous isolates similar to PG50 (c) 14 isolates all serologically similar to Y Goat, but heterogeneously reactive with subsp. capri PG3 and M. capricolum CK antisera (d) 7 isolates serologically similar to subsp. capri PG3, but heterogeneously reactive with subsp. mycoides SC PG1, M. capricolum CK and 2-D antisera (e) 28 isolates strongly reactive with both M. capricolum CK and serogroup 7 PG50 antisera. 119 isolates that were all glucose and arginine negative were also compared by the MF dot method with the reference strains. Most of these could be classified definitely as M. bovis (78 isolates), M. agalactiae (21 isolates) and serogroup 11 (5 isolates). 13 isolates gave a strong reaction with both M. bovigenitalium and serogroup p11 antisera. 2 isolates showed an unclassifiable pattern. The results confirm that the glucose and arginine-negative cluster strains that reacted with 2-D antiserum, also share serological relationships with the "M. mycoides cluster", albeit with a very heterogeneous pattern. PMID- 1455632 TI - Arthroscopic approach and intra-articular anatomy of the palmaroproximal or plantaroproximal aspect of distal interphalangeal joints. AB - An arthroscopic approach to the palmaroproximal or plantaroproximal pouch of the distal interphalangeal joint was developed in six cadaver limbs and seven limbs of three clinically normal horses. The dorsal aspect of the proximal border and the proximal articular margin of the distal sesamoid (navicular) bone, the palmar aspect of the distal articular margin of the middle phalanx, the collateral sesamoidean ligaments of the distal sesamoid bone, and the joint capsule attachments were readily accessible. Distending the joints with fluid gave access to portions of the articular surface between the distal sesamoid bone and the middle phalanx in all joints, and to a small portion of the distal phalanx in two hind distal interphalangeal joints. Two horses allowed to recover from anesthesia were not lame on days 30 and 37, respectively. Problems encountered initially were difficulty entering the joint, hemarthrosis, and minimal iatrogenic cartilage damage. PMID- 1455633 TI - Septic arthritis of the distal interphalangeal joint in 12 horses. AB - The medical records of 12 horses with septic arthritis of a distal interphalangeal joint were reviewed to determine clinical features and response to treatment. Sepsis was caused by trauma or an injection that resulted in an open or contaminated distal interphalangeal joint. All horses were severely lame. Treatment included broad-spectrum parenterally administered antimicrobial drugs (ten horses), percutaneous through-and-through joint lavage (eight horses), indwelling drains (three horses), immobilization of the limb in a cast (three horses), intraarticular injection of sodium hyaluronate (one horse), intraarticular injection of antimicrobial drugs (five horses), curettage of the distal phalanx (one horse), and cancellous bone grafting to promote fusion (one horse). Five horses were euthanatized. Ankylosis of the affected joint developed in five horses, four of which are pasture sound. Two horses treated medically are sound although one underwent subsequent palmar digital neurectomy for treatment of navicular syndrome. PMID- 1455634 TI - Arthroscopic removal of an osteochondral fragment from the middle phalanx of a horse. AB - An intraarticular osteochondral chip fracture of the distal dorsolateral aspect of the right hind middle phalanx in a 4-year-old Dutch Warmblood gelding was removed arthroscopically. Accessibility and visibility of the fragment were excellent, and there was minimal soft tissue trauma. PMID- 1455635 TI - Complete excision of a fractured fourth metatarsal bone in eight horses. AB - Proximal open comminuted fractures of the fourth metatarsal bone (Mt IV) in eight horses were treated by complete removal of the affected bone and antimicrobial therapy. Two horses had concurrent septic arthritis of the tarsocrural or distal tarsal articulations, and five horses had radiographic evidence of osteomyelitis and sequestration of the affected bone. Five horses became athletically sound for their intended use, two horses with septic arthritis had residual lameness but were pasture sound, and one horse was lost to follow-up. Excision of the entire bone appears to be an acceptable treatment of open comminuted fractures of the proximal one-third of Mt IV that do not respond to more conservative modes of therapy. PMID- 1455636 TI - Regional perfusion of the equine carpus for antibiotic delivery. AB - Regional perfusion of carpal tissues by forced intramedullary administration of fluids was evaluated in 10 horses. Results of subtraction radiography after perfusion with a contrast medium demonstrated that perfusate was delivered to the carpal tissues by the venous system. Perfused India ink was distributed uniformly in the antebrachiocarpal and middle carpal synovial membranes. Histologically, the ink was within the venules of the synovial villi. Immediately after perfusion with gentamicin sulfate (1 g), the gentamicin concentrations in the synovial fluid and synovial membrane of the antebrachiocarpal joint were 349 +/- 240 micrograms/mL and 358 +/- 264 micrograms/g, respectively. When gentamicin concentrations in the synovial fluid of the antebrachiocarpal joint and serum were measured 0, 0.5, 1, 4, 8, 12, and 24 hours after carpal perfusion, the mean peak gentamicin concentration in the synovial fluid was 589 +/- 429 micrograms/mL. At hour 24, the mean gentamicin concentration in the synovial fluid was 4.8 +/- 2.0 micrograms/mL. The resulting peak gentamicin concentration in the serum was 23.7 +/- 14.5 micrograms/mL immediately after the perfusion; it decreased below the desired trough level of 1 micrograms/mL between hours 4 and 8. PMID- 1455637 TI - Regional limb perfusion with antibiotics in three horses. AB - Antibiotics were delivered to chronically infected tissues by regional limb perfusion in three horses with osteomyelitis associated with orthopedic implants. Two infections were resolved with implants in place; in one, a sequestrum was resorbed. In one horse, regional antibiotic perfusion was applied to treat progressively worsening bone infection after initial implants loosened and were removed. PMID- 1455638 TI - Evaluation of canine cortical bone graft remodeling. AB - A stable cortical bone fracture model was developed to evaluate the remodeling rate of cortical bone grafts. Samples of cortical bone were harvested with a trephine and press fit into predrilled holes in the femoral diaphyses of four live dogs. The percentages of new bone, unremodeled graft bone, porosity, forming bone surface area, and resorbing bone surface area were determined morphometrically and compared in cortical autografts, cortical allografts sterilized with 84% ethylene oxide (EO), and allografts sterilized with 12% EO. The host-graft interfaces healed without formation of fibrous tissue or cartilage, indicating a stable fracture surface. The amount of new bone formed in cortical autografts and allografts sterilized with 84% EO was significantly greater than the amount of new bone in allografts sterilized with 12% EO. There was no significant difference between the amounts of new bone formed in the allografts sterilized with 84% EO and the cortical autografts. No significant differences were detected in percentages of porosity or bone surface areas. PMID- 1455639 TI - Unilateral and bilateral stifle arthrodesis in eight dogs. AB - Nine stifle arthrodeses in eight dogs were reviewed retrospectively to evaluate use of the limb, each dog's comfort, complications, and factors that may have influenced the final outcome. Ability to use the limb after unilateral fusion was good (limb used at all times) in three dogs, fair (limb used at all gaits except a gallop) in three dogs, and poor (limb used only when running) in one dog. Factors that appeared to affect the outcome included angle at which the stifle was fused and lesions in the ipsilateral coxofemoral joint. One dog with bilateral arthrodesis had a good outcome with minor limitations. The only potentially devastating complications occurred in one dog in which infection and premature implant loosening jeopardized the fusion. None of the dogs exhibited signs of pain and all owners were satisfied with the results. PMID- 1455640 TI - Canine axial skeletal osteosarcoma. A retrospective study of 116 cases (1986 to 1989). AB - Axial skeletal osteosarcomas were evaluated retrospectively in 116 dogs. Thirty one tumors occurred in the mandible, 26 in the maxilla, 17 in the spine, 14 in the cranium, 12 in the ribs, 10 in the nasal cavity and paranasal sinuses, and 6 in the pelvis. Medium-sized and large dogs were most commonly affected. Females outnumbered males 2.1:1, but this varied with tumor location. The mean age was 8.7 years. Osteosarcomas of the rib occurred in significantly younger dogs (mean age, 5.4 years) than osteosarcomas at any other axial skeletal site. Pulmonary metastasis was diagnosed radiographically in 11.1% of the dogs. The median survival for dogs treated surgically was 22 weeks, the 1-year survival was 26.3%, and the 2-year survival was 18.4%. The tumor recurrence rate was 66.7%. Most dogs (79.6%) died or were euthanatized for problems associated with the primary tumor. PMID- 1455642 TI - Minimal anesthetic concentration and cardiopulmonary dose-response of halothane in ducks. AB - The minimal anesthetic concentration (MAC) for halothane and cardiopulmonary dose responses at several concentrations of halothane were determined during spontaneous ventilation in nine young adult Pekin ducks. The MAC for halothane was 1.04 +/- 0.11 (mean +/- SD). There were dose-dependent decreases in ventilation, significant reductions in inspiratory and expiratory times, and prolongation of expiratory pause times. The end-tidal halothane concentration at apnea in five ducks was less than 1.53% and anesthetic index was less than 1.51. Heart rate increased significantly as the concentration of halothane was increased, but arterial blood pressure did not change. Cardiac arrhythmias developed in five ducks at end-tidal halothane concentrations as low as 1.15%, and one duck died of cardiac arrest. PMID- 1455641 TI - Xylazine-ketamine and detomidine-tiletamine-zolazepam anesthesia in horses. AB - Eight horses were anesthetized three times, by intravenous administration of xylazine (1.1 mg/kg) and ketamine (2.2 mg/kg), detomidine (0.02 mg/kg) and tiletamine-zolazepam (1.1 mg/kg), or detomidine (0.04 mg/kg) and tiletamine zolazepam (1.4 mg/kg). The sequences were randomized. The duration of analgesia and the times to sternal and standing positions were recorded. Heart rate, arterial pressure, pHa, PaCO2, and PaO2 were measured before and during anesthesia. The duration of analgesia with the two doses of detomidine-tiletamine zolazepam, 26 +/- 4 minutes and 39 +/- 11 minutes, respectively, was significantly longer than the 13 +/- 6 minutes obtained with xylazine-ketamine. Bradycardia occurred after administration of detomidine, but heart rates returned to baseline values 5 minutes after administration of tiletamine and zolazepam. Arterial pressure was significantly higher and PaO2 significantly lower during anesthesia with detomidine-tiletamine-zolazepam than with xylazine-ketamine. Some respiratory acidosis developed with all anesthetic combinations. The authors conclude that detomidine-tiletamine-zolazepam can provide comparable anesthesia of a longer duration than xylazine and ketamine, but hypoxemia will develop in some horses. PMID- 1455643 TI - Measurement of tracheal static pressure in exercising horses. AB - A nasotracheal catheter for measuring tracheal static pressure in exercising horses was designed according to aerodynamic engineering principles. Small ports near the end of the catheter transmitted pressure fluctuations to the recording apparatus. Accuracy was determined by the size, number, and location of pressure sensing holes on the catheter, and by the position of the catheter in the trachea. The catheter had adequate frequency response to 33 Hz, was insensitive to movement artifacts, was easily introduced, was tolerated well by horses, and resulted in small ventilatory impairment at maximal exertion. PMID- 1455644 TI - The anatomic basis for a trapezius muscle flap in dogs. AB - The anatomy of the cervical part of the trapezius muscle and its dominant vascular supply, the prescapular branch of the superficial cervical artery, was studied by dissection and selective angiography of 16 canine cadavers. The prescapular branch of the superficial cervical artery supplies blood to the skin of the caudal half of the neck and the cervical part of the trapezius muscle and is a minor contributor to other muscles of the neck. In these dogs, the mean length of the vascular pedicles was 4.4 cm and the mean diameter was 1.0 mm. With this information, it is possible to design a broad musculocutaneous flap suitable for reconstructive microsurgery in dogs. The potential for successful incorporation of the scapular spine in such a flap remains uncertain. PMID- 1455645 TI - Free microvascular transplantation of the trapezius musculocutaneous flap in dogs. AB - A musculocutaneous flap based on the prescapular branch of the superficial cervical artery and including the cervical part of the trapezius muscle and overlying skin was transplanted over a defect created on the medial side of the contralateral tibia in four dogs by using microvascular technique. The donor and recipient sites in three dogs were examined clinically for 21 days, after which they were examined angiographically and histologically. All dogs were free of lameness by hour 48. Seromas formed at the donor site between days 7 and 15. One vascular pedicle was traumatized at hour 40, and the dog was euthanatized. Three flaps survived with minimal necrosis. Edema of the flaps was severe from days 5 to 11. Angiograms showed complete perfusion of the flaps, and survival was confirmed histologically. Esthetic appearance and function were good in one dog at month 7. PMID- 1455646 TI - Closed transventricular dilation of discrete subvalvular aortic stenosis in dogs. AB - Discrete subvalvular aortic stenosis with peak systolic pressure gradients of more than 60 mm Hg was treated by closed transventricular dilation in six young dogs. Peak systolic pressure gradients were measured by direct catheterization before surgery, immediately after dilation, and 3 months after surgery. Maximum instantaneous pressure gradients were measured by continuous wave Doppler echocardiography before surgery and 6 weeks to 9 months after surgery. All dogs survived the procedure, and two dogs were clinically normal after 9 and 14 months. Two dogs died at week 6 and month 7. One dog was receiving medication for pulmonary edema 15 months after surgery. One dog underwent open resection of the subvalvular ring at month 3, and was clinically normal 6 months after the second procedure. Complications included intraoperative ventricular fibrillation in one dog, and mild postoperative aortic insufficiency in one dog. Closed transventricular dilation resulted in an immediate 83% decrease in the peak systolic pressure gradient from a preoperative mean of 97 +/- 22 mm Hg to a mean of 14 +/- 15 mm Hg. However, systolic pressure gradients measured by direct catheterization at month 3 (77 +/- 26 mm Hg), and by Doppler echocardiography at week 6 to month 9 (85 +/- 32 mm Hg) were not significantly different from preoperative values, which suggested recurrence of the aortic stenosis. Closed transventricular dilation should not be considered a definitive treatment for discrete subvalvular aortic stenosis in dogs, but may be useful in young dogs with critical aortic stenosis as a bridge to more definitive surgery. PMID- 1455647 TI - Temporary bile diversion in cats with experimental extrahepatic bile duct obstruction. AB - The use of a cholecystostomy catheter for temporary bile diversion was investigated in four cats with experimentally induced extrahepatic bile duct obstruction. Eighteen days after ligation of the common bile duct, a 6.5 F accordion catheter was placed in the gallbladder with a 22 g Hawkins needle-guide system through a paracostal incision. Biochemical parameters and fasting serum bile acids were monitored for 16 days. There were significant decreases in mean total bilirubin, aspartate aminotransferase, and fasting serum bile acids within 72 hours of bile diversion, and in mean alanine aminotransferase within 96 hours. Attitude and appetite improved, and the catheter was tolerated well. Positive bile cultures developed in three cats. Histologic changes in the gallbladder included mucosal ulcerations, a mixed inflammatory cellular infiltration, and fibrosis of the submucosa. PMID- 1455648 TI - Exploratory celiotomy in 200 nontraumatized dogs and cats. AB - Two hundred dogs and cats undergoing exploratory celiotomy for reasons other than trauma were grouped by disease classification and by body system affected. There were 61 animals in which infection or inflammation predominated, 63 animals with neoplasia, and 76 animals with noninflammatory and non-neoplastic conditions. Body systems affected were digestive, lymphatic, urinary, reproductive, other, and undetermined. Seventy-three percent of the animals survived the hospitalization period; survival rates for animals with infection or inflammation, neoplasia, and other disorders were 69%, 60%, and 86%, respectively. Within the same groups, the exploratory celiotomy provided strictly diagnostic information in 72%, 79%, and 24% of the animals, and surgical treatment was provided to 28%, 21%, and 58% of the animals, respectively. Intraoperative cytologic and histologic diagnoses were consistent in 78% of the animals; the consistency rates for animals with infection or inflammation, neoplasia, and other disorders were 81%, 88%, and 59%, respectively. Complications after surgery were observed in 30% of the animals, with 60% of the complications disease related. Complications were observed in six animals with reproductive disorders (67%), six animals with urinary disease (46%), 35 animals with digestive disease (29%), and three animals with lymphatic disease (13%). PMID- 1455649 TI - Comparison of an antimicrobial adhesive drape and povidone-iodine preoperative skin preparation in dogs. AB - The antimicrobial efficacy of an adhesive drape applied after a 1-minute alcohol scrub was compared to a povidone-iodine (PI) skin preparation technique in dogs. Each technique was applied to both sides of 15 adult anesthetized dogs on premeasured, clipped areas of skin. Skin bacteria were quantified before, immediately after, and 1 hour after skin preparation. Predominant skin bacteria were isolated by swabbing the skin. The percentages of bacterial reduction immediately after and 1 hour after skin preparation, percentages of negative culture results, cultures with more than five colony-forming units, and the frequency of skin reactions were calculated and analyzed statistically. Drape adhesion was assessed subjectively. The percentage reduction in skin bacteria was significant for both techniques and comparable to that reported in humans. The adhesive drape was significantly less effective in both the immediate and 1-hour periods. Lift occurred in 66% of drape applications but was not associated with high bacterial counts. Acute contact dermatitis was more frequent after skin preparation with PI. There was no difference between the techniques in recovery of potential skin pathogens. The authors conclude that application of this antimicrobial adhesive drape after a 1-minute alcohol scrub is not as effective in the reduction of skin bacteria in dogs as is PI preparation of the skin. PMID- 1455650 TI - Anaerobic bacteria isolated from osteomyelitis in dogs and cats. AB - Anaerobic bacteria were isolated from 18 of 28 animals (64%) with osteomyelitis. The bones most commonly infected with anaerobic bacteria were radius and ulna, mandible, and tympanic bulla. Fights or abscesses commonly preceded the osteomyelitis. Seven anaerobic genera were isolated. Mixed infections of anaerobic and aerobic organisms occurred in 16 animals. Staphylococci were isolated in only one such mixed infection, but they were isolated commonly when there were aerobic bacteria only. Staphylococcal infections were often single. PMID- 1455651 TI - Replacement of the medial collateral ligament with polypropylene mesh or a polyester suture in dogs. AB - The medial collateral ligament of one stifle in 20 adult dogs was excised and replaced with polypropylene mesh or a polyester suture. After 26 weeks, the fibrous tissue-prosthesis composites were evaluated clinically, morphologically, and biomechanically. Clinical lameness was not significantly different after 10 days. The polypropylene mesh reconstructions consistently had more fibrous tissue and greater collagenous ingrowth than the polyester suture reconstructions. There were four complications related to fixation of the polypropylene mesh prosthesis and one to the polyester suture. The polypropylene mesh reconstructions had greater stability and were biomechanically more similar to the natural ligaments than the polyester suture reconstructions. Although the results with polypropylene mesh were favorable, more challenging biomechanical testing and alternative anchoring techniques are required before polypropylene mesh can be recommended as a collateral ligament replacement in dogs. PMID- 1455652 TI - A retrospective evaluation of stifle osteoarthritis in dogs with bilateral medial patellar luxation and unilateral surgical repair. AB - The effects of surgical and nonsurgical therapy on the development of osteoarthritis were compared in 12 dogs with bilateral medial patellar luxation and unilateral surgical repair. Evaluations included severity of lameness and patellar luxation, ligamentous stability, range of motion, and radiographic evidence of osteoarthritis before surgery and at a mean of 33 months after surgery. Stifles without surgical treatment served as controls for the contralateral stifles with surgery. All stifles treated surgically had reduced patellofemoral joints, normal range of motion, and improved limb use. Osteoarthritis progressed significantly and comparably in both groups of stifles. Progression of osteoarthritis was not correlated with luxation grade, body weight, or interval from surgery to follow-up. Age at surgery was correlated positively with severity of osteoarthritis in the stifles treated surgically. PMID- 1455653 TI - Distraction osteogenesis using modified external fixation devices in five dogs. AB - Distraction osteogenesis was used to treat five dogs with limb deformities or limb shortening. The affected bones underwent osteotomy, and modified external fixators were attached. Complications included pin loosening, implant breakage, and soft-tissue contracture. Adequate limb length was attained in all cases, but clinical results varied from poor to excellent. Two dogs were not lame after the procedure, two dogs had improved function but were still lame, and one dog had complications necessitating amputation. PMID- 1455654 TI - Measurement of muscle surface capillary blood flow by laser Doppler flowmetry. AB - Muscle surface capillary blood flow was measured in the biceps femoris and lateral head of the triceps brachii muscles in six horses before and during halothane anesthesia by using laser Doppler flowmetry. During 90 minutes of anesthesia, muscle surface capillary blood flow was reduced to 20% to 40% of preanesthetic values. Muscle surface capillary blood flow tended to be lower in dependent muscles than in nondependent muscles, and this disparity was greater in the forelimbs than in the hind limbs. PMID- 1455655 TI - Effects of 5% and 10% guaifenesin infusion on equine vascular endothelium. AB - Twelve horses of various breeds and either sex were anesthetized with xylazine and ketamine injected into a median or lateral thoracic vein. During anesthesia, with the horse in sternal recumbency, a 14-gauge, 8.9 cm catheter was inserted into each jugular vein by using aseptic technique. Guaifenesin in water (100 mg/kg or a maximum dose of 50 grams) was infused into one jugular vein and an equal volume of 0.9% saline solution was infused into the other jugular vein. Seven horses received 10% guaifenesin, and five horses received 5% guaifenesin. The catheters were removed before the horses recovered from anesthesia. The horses were euthanatized approximately 48 hours later, and the jugular veins were removed for histologic examination. Adherent thrombus material was observed in all veins exposed to 10% guaifenesin and in one vein exposed to 5% guaifenesin. No evidence of thrombus was observed in four veins infused with 5% guaifenesin or in those infused with saline solution. These findings are of particular significance with horses at increased risk for thrombosis or thrombophlebitis. PMID- 1455656 TI - [Potentialities of ultrasound and computed tomography in the diagnosis of metastases of lung cancer in the mediastinal lymph nodes]. AB - The results of routine roentgenotomography, CT and USI in the diagnosis of intrathoracic metastases of lung cancer were compared in 69 patients (central type--52, peripheral--17). These results were compared with operative findings in 45 patients. The sensitivity of USI in the diagnosis of enlarged paravasal lymph nodes exceeded that of roentgenotomography and was slightly inferior to CT. CT was informative for all mediastinal lymph nodes whereas tomography and USI were informative in certain areas only. The authors recommend to combine the use of routine and ultrasound tomography to assess the spreading of lung cancer to the mediastinum. The information obtained increases the accuracy of staging and specifying a process, slightly yielding CT results. PMID- 1455657 TI - [Ultrasonography and computed tomography in the detection of overlooked gauze surgical dressings]. AB - USI and CT were performed in 14 patients with textile foreign bodies left in the abdominal cavity and retroperitoneal space during operation on the biliary tracts (6 cases), kidneys (4 cases), pancreas (2), stomach (1), and during appendectomy (1). A decisive sign in USI that enabled one to detect gauze foreign bodies, was a stable echogenic zone corresponding to a proximal body contour with a solid acoustic shadow behind. Extra-organic localization of these changes contributed to making diagnosis. A certain amount of fluid could be seen around a foreign body during an exudative reaction. In CT, diagnosis was based on the detection of a formation with a capsule containing calcinates and air masses. PMID- 1455658 TI - [Potentialities of lymphography using chromethiotrast, a new x-ray contrast medium]. AB - A study was made of the potentialities of lymphography using a new radiopaque medium chromethiotrast (a solution of harmless fat-soluble anthraquinone dyes fixed with ethiotrast). The agent is intended for combined x-ray and visual investigation of the lymphatic system. Lymphograms of 76 patients (with Hodgkin's disease, prostatic cancer, cancer of the female organs, breast, bladder, rectal cancer, and secondary limb lymphedema) were analyzed. Chromethiotrast is easily administered in the lymphatic bed ensuring a good contrast density of the lymphatic vessels permitting the detection of their structure. Chromethiotrast is quickly discharged from the lymphatic system, causing no marked side-effects provided all precautions necessary for the administration of iodobutyric radiopaque media, are taken. PMID- 1455659 TI - [Early x-ray diagnosis of hip dysplasia in children]. AB - The author proposes a method of differential diagnosis of hip dislocations and hip joint dysplasia in infants aged 3 months. The alpha-angle of hip dislocation with relation to trochanteric space is determined on an anteroposterior radiogram of the hip joints; 64 degrees means hip dysplasia, 65-69 degrees and more mean dislocation. This method was tested in 75 children (150 joints) aged 3 months. A mean diagnostic accuracy was 90.1%. PMID- 1455660 TI - [Arthrography in congenital hip dislocation]. AB - The paper is concerned with the results of contrast arthrography in 73 children with hip joint dysplasia, among which true dislocations prevailed (70 patients). In addition to bone alterations, arthrography revealed various soft tissue changes like hypertrophy and deformity of limbus, soft tissue interposition, separation of the articular sac with the presence of an isthmus, disintegration of articular cartilages. These findings are used to define indications for surgical intervention as well as for planning the area of operation. PMID- 1455661 TI - [X-ray diagnosis of ruptures of the distal radioulnar joint]. AB - The paper describes 42 intact, 14 damaged and 52 ruptured radioulnar joints. The joints width was measured, the radioulnar index calculated, x-ray pictures filtered. Variants of isolated injuries of the joints in different bone dislocation, changes in combined ruptures and injuries are described. The radioulnar index proved the best in quantitation of the joint damage. PMID- 1455662 TI - [Ossification of the posterior longitudinal ligament]. AB - The authors described 21 patients aged 37 to 83 with ossification of the posterior longitudinal ligament (10 with ischemic myelopathy, 6 with aftermaths of a trauma of the cervical spine, and 5 with the radicular syndrome on the basis of vertebral osteochondrosis. X-ray signs of three types of ossification of the posterior longitudinal ligament were defined and specified: linear, curved and mixed. The linear type was more frequently observed in the cervical spine whereas the curved type was more frequent in the lumbar spine. PMID- 1455663 TI - [An x-ray study in the diagnosis of rotator cuff injuries]. AB - The author has studied 142 x-ray films and 132 arthrograms of patients with various lesions of the rotator cuff and has found that in none of the cases has a correct roentgenological diagnosis been made outside his own department. The main routine x-ray and arthrographic signs of such lesions are described. The conclusion is made that in spite of inability of each particular x-ray method to reveal precise dimensions of the gap of the rotator cuff a combined roentgenological examination permits one to determine indications to surgery and elaborate an adequate operative strategy. PMID- 1455664 TI - [X-ray diagnosis of hemophiliac pseudotumors]. AB - Of 259 hemophiliacs bone pseudotumors were diagnosed in 11 (4.3%); they were localised in the femur (6 cases), calcaneus (4) and in the iliac bone (3). Two cases of combined femoral and calcaneal lesions and 4 cases of bone fracture were observed. As a rule, pseudotumors developed in hemophiliacs with severe disease. An x-ray picture of a pseudotumor depended on its site and was characterized by a large soft tissue tumor shadow, often with calcinosis, and serious destructive changes in bones in the form of round foci of 7 cm in diameter with clear-cut contours. An edge defect of the cortical layer was defined in the diaphysis of the femoral bone (15 cm long). Destructive changes were often accompanied by osteosclerosis and periostitis. PMID- 1455665 TI - [Water-soluble contrast media with increased viscosity for the diagnosis of diseases of the paranasal sinuses, bronchi and esophagus]. AB - Water-soluble contrast agents with one of the polymers, cellulose derivatives or polyvinyl alcohol, were used in contrast examinations of paranasal sinuses, bronchi, and esophagus. Experiments have demonstrated the advantages of contrast agents basing on polymers as against the traditional oil-containing agents. Method for double-contrast examination of maxillary and frontal sinuses has been developed. Lowered concentrations of water-soluble contrast agents (i. e. diluted with distilled water) are recommended to be used, this permitting to save the reagents. A table of recommended dilutions of contrast media is presented. A total of 245 patients were examined, making use of contrast media of high viscosity. PMID- 1455666 TI - [An x-ray study of the subcutaneous tissue using an artificial method of providing contrast]. AB - The paper is concerned with the main methodological principles and potentialities of a radiocontrast study of subcutaneous fat to detect pathological changes in it. The proposed method consists in slow administration in the middle fat layers of 20-25% solution of verografin from not less than two points, and subsequent roentgenography in a necessary projection. The method was used in 15 patients with various orthopedic diseases for diagnosis of inflammatory, tumorous and degenerative-dystrophic diseases. PMID- 1455667 TI - [The toxic autoimmune syndrome with pulmonary edema]. PMID- 1455668 TI - [Ultrasonic tomography of para-appendicular and post-appendectomy abscesses]. PMID- 1455669 TI - [Iatrogenic embolization of the upper mesenteric artery--a complication of interventional embolotherapy]. PMID- 1455671 TI - [A removable compression tube]. PMID- 1455670 TI - [A disintegrating lung tumor]. PMID- 1455672 TI - [The diagnosis of epithelioid leiomyoma]. PMID- 1455673 TI - [The differential diagnosis of acute appendicitis]. PMID- 1455674 TI - [Osteoplastic tracheobronchopathy. Diagnosis using CT]. PMID- 1455675 TI - [A case of rhabdomyosarcoma of the lung]. PMID- 1455676 TI - [A case of the diagnosis of a teratoma of the thymus gland using magnetic resonance tomography]. PMID- 1455677 TI - [The present status and future of the development of the material and technologic basis of radiography and radiology]. PMID- 1455678 TI - [An atypically located hypoplasia of a lung lobule in a child, wrongly diagnosed as a tumor of the posterior mediastinum]. PMID- 1455679 TI - [Videodensitometric analysis of x-ray contrast images]. PMID- 1455680 TI - Depressed potential for interleukin-2 production following early weaning of piglets. AB - Spleen cells, but not mesenteric lymph node cells, from 3-week-old piglets abruptly weaned onto a soya-based diet, produced less interleukin-2 (IL-2) following non-specific activation with concanavalin A (Con A) than did cells from age- and litter-matched, unweaned controls. In contrast, the ability to express receptors for IL-2 was only marginally reduced. The effect on IL-2 production was most marked in animals weaned for as little as 24-48 h. Variation within groups increased with time after weaning, indicating differences between individuals in the longer-term effects of weaning. This finding may be due to endogenous production of steroids resulting in generalised impaired immune function or to retention of cells within intestinal sites owing to an active local immune response. PMID- 1455681 TI - Characterization of porcine xenoreactive cytotoxic T lymphocytes. AB - Cytotoxic T lymphocytes (CTL) against mouse P815 cells were detected after stimulation of porcine peripheral blood mononuclear cells (PBMC) with irradiated Balb/c splenocytes. In vivo priming prior to in vitro stimulation slightly enhanced CTL activity, but lysis of targets was undetectable from lymphocytes from non-immune or immune animals that were not cultured with mouse splenocytes. After primary culture with Balb/c (H-2d) splenocytes, specific killing of P815 (H 2d) targets and not L929 (H-2k) targets indicated that recognition was specific for the H-2 locus. Similarly, CTL primed by mouse cells from either of two congenic strains recognized targets with alleles homologous to the stimulating cells. The anti-murine CTL was confirmed to be a CD8+ T cell based on studies using specific monoclonal antibodies to the porcine CD4 or CD8 cells. The cells responsible for the cytotoxicity of P815 targets lacked the characteristics of non-specific NK cells because (1) naive PBMC were unable to lyse NK targets (K562 cells) during the 4 h cytotoxic assay and (2) CTL killing of P815 targets increased with time after primary stimulation, whereas killing of K562 cells remained low at all times. These results suggest that porcine CTL can be readily generated against the xenogeneic mouse major histocompatibility complex. PMID- 1455682 TI - Cross-reactivity of monoclonal antibodies to bovine immunoglobulins with immunoglobulins of other species. AB - Monoclonal antibodies (Mabs) to bovine immunoglobulin heavy chain of the four major isotypes gamma 1, gamma 2, alpha, mu and the light chains (combined kappa and lambda) were produced and found to cross-react in enzyme-linked immunoassay (ELISA) with immunoglobulins of some other animal species despite the discrete specificity associated with an antibody derived from a single clone. This cross reactivity, particularly amongst ruminants, could be utilized in serological testing for the diagnosis of disease in these species. For example, Mabs produced against bovine immunoglobulin light chain cross-react with bison immunoglobulin light chain and were used successfully in serological testing as the secondary detection antibody in an indirect ELISA for the diagnosis of Brucella abortus in bison herds in north-western Canada. PMID- 1455683 TI - A comparative study on the use of bovine and murine monoclonal antibodies for passive immunization in cattle. AB - In the present experiments the efficacy of murine and bovine monoclonal antibodies for passive immunization in cattle was compared. The in vivo immunoneutralization of pregnant mare serum gonadotrophin (PMSG) by murine and bovine antibodies after repeated administration was chosen as a model for this study. Results indicate that repeated injections of murine monoclonal antibodies against PMSG (mMCA) alone did not, or only to a small extent, elicit an anti mouse immune response. The simultaneous administration of mMCA and PMSG resulted in relatively high levels of anti-mouse antibodies after the second injection, leading to a decrease in neutralizing activity of mMCA. The results suggest that the neutralizing activity of mMCA is inhibited more by anti-idiotypic than by anti-isotypic antibodies against mMCA. In vivo, the bovine monoclonal antibody against PMSG (bMCA) only partially neutralizes PMSG. After repeated administration of bMCA, either alone or in combination with PMSG, no anti-bMCA antibodies could be detected in our assay system. In addition, no change in plasma levels of bMCA and PMSG compared with levels after the first injection was observed. Although it has to be confirmed by further experiments whether our findings can be generalized, the present results suggest that for repeated passive immunization in cattle homologous antibodies are to be preferred above heterologous antibodies. PMID- 1455684 TI - Engraftment of severe combined immune deficient/beige mice with bovine foetal lymphoid tissues. AB - To develop a model of bovine thymus and lymph node growth in vivo, we have implanted bovine foetal tissues (16-23 weeks gestation) under the renal capsule of severe combined immune deficient (SCID)/beige (BG) mice and assayed for graft growth and characteristics 2-18 weeks after engraftment. Bovine foetal thymus and lymph node grew considerably following engraftment of SCID/BG mice. Growth was optimal if bovine foetal tissues were used before gestation Week 17. Bovine-mouse chimerism was confirmed using glucose phosphate isomerase analysis. Bovine thymus grew during the entire 18 weeks of study. Growth of bovine lymph node was initially rapid, reaching a maximum at 2 weeks after transplantation followed by a progressive decrease in size. Transplanted bovine lymph node and thymus were morphologically similar to age-matched bovine foetal tissue for a limited time period. Fibrosis, degeneration and depletion of lymphocytes were evident 6 weeks after engraftment; changes were more severe in lymph node than in thymus whereas increases in lymphocytes, lymphopoiesis and follicle formation were evident in age-matched bovine foetal tissue. Despite growth and morphological similarities of the transplanted tissue, blood counts suggested there was no peripheralization of bovine leucocytes. Bovine immunoglobulins (IgG1 and IgG2) were detected in serum of some SCID/BG chimeric mice for a limited time. The appearance of bovine immunoglobulins at 2 weeks in SCID/BG chimeric mice depended on the age of the foetal donor (> 18 weeks) and coincided with the appearance of morphologically mature lymphocytes in the donor foetus lymph nodes. The ability to produce bovine immunoglobulins decreased 8 weeks after engraftment, coinciding with the depletion of lymphocytes in the engrafted lymph node. Lymphocyte depletion and loss of function of engrafted tissues appear the result of a lack of lymphoid progenitors normally derived from hematopoietic stem cells in the bone marrow. PMID- 1455685 TI - The long-term culture of bovine monocyte-derived macrophages and their use in the study of intracellular proliferation of Brucella abortus. AB - Although the immune response to Brucella abortus is multifaceted, the key event in contending with this pathogen appears to be the interaction of the organism with cells of the mononuclear phagocyte system. A cell culture system was developed which allowed the long-term maintenance of blood monocyte-derived macrophages in Teflon culture vessels in a relatively unstimulated state. The assay system was optimized for timing of bacteria-macrophage interaction and numbers of bacteria and macrophages used in each assay. Interaction of B. abortus strain 2308 with bovine mononuclear phagocytes from animals phenotypically resistant and susceptible to infection with B. abortus was investigated. This cell culture and assay system should provide a useful model for the investigation of intracellular parasitism in cattle. PMID- 1455686 TI - Protective efficacy of conjugate vaccines against experimental challenge with porcine Actinobacillus pleuropneumoniae. AB - In an attempt to protect pigs against swine pleuropneumonia induced by Actinobacillus pleuropneumoniae (SPAP) by neutralizing the effects of three virulence factors of A. pleuropneumoniae--the capsular polysaccharide (CP), the lipopolysaccharide (LPS), and the hemolysin protein (HP)--two subunit conjugate vaccines were prepared by covalently coupling the CP to the HP and the LPS to the HP. The CP, LPS, and HP were isolated from A. pleuropneumoniae, strain 4074, serotype 1, and the protective efficacy of the conjugate vaccines in swine experimentally infected with A. pleuropneumoniae was evaluated. Following a booster vaccination, a significant (P < 0.05) IgG antibody response to the CP, LPS, and HP was detected in the vaccinated pigs. The pigs vaccinated with the CP HP and LPS-HP conjugates exhibited significantly less mortality (P < 0.05) and significantly greater weight gain (P < 0.001) than unvaccinated pigs. Vaccinated pigs exhibited significantly fewer and less extensive gross pulmonary lesions (P < 0.001) when compared with unvaccinated pigs. Thus, on the basis of mortality, weight gains, and pulmonary lesion formation, the two conjugate vaccines used in conjunction with one another provide noticeable protective efficacy against SPAP. PMID- 1455688 TI - Duck lymphocytes. VI. Requirement for phagocytic and adherent cells in lymphocyte transformation. AB - Preparations of duck (Anas platyrhynchos) spleen and blood lymphocytes depleted of cells capable of phagocytosing carbonyl iron gave lower transformation responses to the mitogens phytohaemagglutinin (PHA), concanavalin A (Con A), Bandeiraea simplicifolia seed lectin (BSS), wheat germ agglutinin (WGA), lentil lectin (LL) and phorbol ester (PMA) than intact cell preparations. When cell populations were fractionated on the basis of their adherence to plastic, it was found that the adherent cells were responsive to PHA, Con A, BSS, WGA and PMA, while the non-adherent cells responded to LL. These observations confirm the expected requirement for phagocytic accessory cells in the induction of in vitro mitogen-driven duck lymphocyte responses. The responses of plastic-adherent populations of cells to most mitogens are believed to reflect the generally close physical relationship between the adherent accessory cells and the lymphocytes, although it remains possible that duck monocytes respond to some of the mitogens employed. The data also suggest that LL stimulates a population of cells different to those responding to other mitogens. PMID- 1455687 TI - Ivermectin: its effect on the immune system of rabbits and rats infested with ectoparasites. AB - The influence of subcutaneously administered ivermectin on the specific immune response was studied in rabbits infested with mites (Psoroptes cuniculi) and in rats infested with lice (Polyplax spinulosa). A pronounced specific antibody activity and a change in immunoblotting pattern was observed in rabbits after the ivermectin treatment. However, in rats the antibody activity decreased and the profile of specific antibodies, tested by immunoblotting, remained the same as before the treatment. The specific immune response in rabbits artificially immunized with whole-body Psoroptes cuniculi extract was not affected by ivermectin. It was concluded that ivermectin has no direct effect on the immune response of rabbits and rats and that the enhanced immune response in the mite infested rabbits was caused by the massive release of antigens associated with the synchronous death of the mites. PMID- 1455689 TI - Prognostic implications of bone marrow features in chronic myelogenous leukaemia. PMID- 1455690 TI - Changes of silver-stained nucleolar organizer regions in mouse endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17 beta-oestradiol. AB - A high incidence of endometrial adenocarcinoma and pre-neoplastic lesions was induced in ICR mice treated with N-methyl-N-nitrosourea and 17 beta-oestradiol within 23 weeks. The endometrial lesions were histopathologically similar to those of human subjects. To assess the cell proliferative activity of these lesions, a one-step silver colloid staining for nucleolar organizer regions was applied and the numbers of silver-stained nucleolar organizer regions (AgNORs) were counted. The mean numbers +/- SD of AgNORs in each lesion were as follows: simple hyperplasia, 2.07 +/- 0.36; complex hyperplasia without cytological atypia, 2.79 +/- 0.39; complex hyperplasia with cytological atypia, 3.43 +/- 0.38; and well-differentiated adenocarcinoma, 4.17 +/- 0.40. Significant differences were observed in each lesion (P < 0.001). These findings suggest that the mean numbers of Ag-NORs are increased in the progression of neoplastic changes in the mouse endometrium, as in human endometrial lesions. This rapid induction model of endometrial carcinoma in mice is useful in the understanding of the histogenesis of endometrial carcinoma in human subjects. PMID- 1455691 TI - Immunohistological analysis of tumour infiltrating lymphocytes in seminoma using monoclonal antibodies. AB - Immunological characterization of tumour infiltrating lymphocytes (TIL) by immunohistological techniques was carried out in 20 cases of stage I seminoma. Routine pathological examination of these surgical specimens showed typical seminoma in 20 cases. Eighteen cases showed obvious TIL and immunohistological staining on frozen specimens was performed in 12. TIL in seminomas were predominantly T-cells but B-cells were also identified. T-cells were distributed diffusely with predominance of the CD8+ phenotype judged semiquantitatively. In contrast to the distribution of T-cells, B-cells tended to accumulate and occasionally formed lymphoid follicles. In such follicles the phenotypic pattern of B-cell antigens was comparable with secondary lymphoid follicles in lymphoid organs. There is an immunologically complex response to seminoma by the host with a predominant infiltration of cytotoxic/suppressor T-cells and functional maturation of B-cells. PMID- 1455693 TI - Interneuronal interaction between members of quadrature phase and anti-phase pairs in the cat's visual cortex. AB - Interactions between adjacent simple cells recorded simultaneously from the same microelectrode placement were studied by correlational analysis. The receptive fields of pairs of such cells exhibit either 90 degrees (quadrature phase) or 180 degrees (anti-phase) phase relationships. We now show that the majority of quadrature phase pair members do not receive common input from the immediately precedent stage along the visual pathway, nor do these cells interact with each other. The anti-phase pairs show relatively strong mutual inhibition. These results suggest that each of the physically adjacent phase-related simple cells receives excitatory input from a distinct group of pre-cortical cells, and that mutual inhibitions between members of anti-phase pairs are used to construct the inhibitory subzones of these cells. We propose a model which incorporates these new results and provides a parsimonious explanation for the construction of both quadrature phase and anti-phase pairs. PMID- 1455692 TI - Paramyxovirus-like nuclear inclusions identical to those of Paget's disease of bone detected in giant cells of primary oxalosis. AB - Nuclear inclusions, identical to those characteristic of Paget's disease of bone, were observed in giant cells in four of eight cases of primary oxalosis. The giant cells containing nuclear inclusions were directly involved in phagocytosis of large oxalate crystals in the context of typical foreign body granulomas in the bone marrow. Cytochemically, all of them exhibited strong tartrate-resistant acid phosphatase activity, and a proportion of them also tartrate-resistant acid ATPase. The inclusions consisted of typical arrays of filamentous material as described in Paget's disease, admixed with variable proportions of electron-dense material closely reminiscent of nucleolar pars fibrillaris and fibrillary centres. These data indicate: (a) the occurrence of Paget-like inclusions in a bone disease unrelated to Paget's disease, not causally related to viral infection, and resulting from an inborn metabolic derangement; and (b) the occurrence of Paget-like inclusions in foreign body giant cells as opposed to osteoclasts. We suggest that the occurrence of paramyxovirus-like nuclear inclusions in either osteoclasts or giant cells may represent an epiphenomenon of cell fusion and giant cell formation whenever appropriate stimuli act on latently infected precursor cells. Furthermore, our data suggest that nucleoli may represent the specific site of virus-like inclusion formation. PMID- 1455694 TI - The effects of aging on the pattern electroretinogram and visual evoked potential in humans. AB - We have recorded patterns electroretinograms (PERGs) and visual evoked potentials (VEPs) from 14 elderly subjects (mean age 72 yr) and 12 young subjects (mean age 21 yr) in response to stimulation by high contrast sinusoidal grating patterns of variable spatial frequency (at 9 Hz) and temporal frequency (at 1.7 c/deg). The major effect of aging on the PERG was an aspecific reduction in amplitude (of about 40%) at most spatial and temporal frequencies, together with a small but systematic phase lag. Control measurements suggest that senile miosis may be responsible for the phase lag, but not for the reduction in amplitude. The effects of aging on the VEP were more dramatic and depended on the spatial and temporal properties of the stimulus. VEP amplitudes (at 1.7 c/deg) were significantly lower for the aged at low temporal frequencies (below about 6 Hz), but were similar at high temporal frequencies. At 9 Hz, there was no effect of spatial frequency on VEP amplitude. At high temporal frequencies (above 10 Hz), the latencies of VEPs (estimated from the rate at which phase varied with temporal frequency) were similar for old and young (94 and 99 msec respectively). Below 10 Hz, however, the latencies of the old observers was much greater (153 compared with 108 msec). The second-harmonic phase of VEPs of the old but not the young decreased considerably with spatial frequency, by about 1.9 pi radians (52 msec) over the range from 0.5 to 11 c/deg. The selective reduction in amplitude at low temporal frequencies, the longer latencies at low temporal frequencies and the phase lag at high spatial frequencies are consistent with the hypothesis that mechanisms sensitive to high spatial and low temporal frequencies are selectively degraded by aging. PMID- 1455695 TI - Effect of light scatter on the pattern reversal visual evoked response: comparison with psychophysical results. AB - The effect of light scatter on the pattern reversal visual evoked response (PVER) was studied in 6 normal subjects. The results were compared with contrast visual acuity, contrast sensitivity function, and glare disability. Light scatter was induced by translucent acrylic sheets. Visual acuity measured with the low contrast charts decreased significantly (P < 0.0001) even with a small degree of light scatter. Contrast sensitivity decreased with a small degree of light scatter especially for high spatial frequencies. PVER amplitudes decreased especially at the smaller checks with its peak shifted to larger checks. PVER was equally sensitive to light scatter compared to psychophysical tests. PMID- 1455696 TI - Retinal and cortical activity in human subjects during color flicker fusion. AB - Pattern electroretinograms (PERG) and cortical visually evoked potentials (VEP) were simultaneously recorded from 7 visually normal and 1 protanopic subjects. Stimuli were color checkerboards (0.5 degrees check size), phase-reversing at 17 Hz (i.e. 34 reversals/sec). Using a stepwise sweep procedure, the luminance of the red (lambda peak = 550 nm) and green (lambda peak = 630 nm) checks varied in 11 steps in opposite directions from 0 to 30 cd/m2, embracing the subjective equiluminance point. For normal subjects at subjective equiluminance, the VEP amplitude dropped sharply down to 13 +/- 2% of the value at pure luminance contrast. The PERG, however, was only reduced to 56 +/- 10% at this point, an attenuation 4 times less than that of the VEP. In contrast to normal subjects, in the protanopic subject the PERG was sharply reduced at equiluminance, parallel to the VEP. This would be expected when L-cones are missing. Assuming that the PERG reflects the activity of the retinal ganglion cells, our findings suggest that human retinal ganglion cells respond well under the condition of equiluminant flicker fusion, which is in agreement with recent single-cell studies in the monkey. Consequently, the temporal low-pass filter, which mediates color-flicker fusion, would seem to lie central to the retinal ganglion cells. PMID- 1455697 TI - Three-dimensional properties of human pursuit eye movements. AB - For any given location and velocity of a point target, there are infinitely many different eye velocities that the pursuit system could use to track the target perfectly. Three-dimensional recordings of eye position and velocity in 8 normal human subjects showed that the system chooses the unique tracking velocity that keeps eye position vectors (a particular mathematical representation of three dimensional eye orientation) confined to a single plane, i.e. pursuit obeys Listing's law. One advantage of this strategy over other possible ones, such as choosing the smallest eye velocity compatible with perfect tracking, is that it permits continuous pursuit without accumulation of ocular torsion. For nonpoint targets, there is at most one eye velocity compatible with perfect retinal image stabilisation, and the optimal velocity may not fit Listing's law; we observed small but consistent deviations from the law during pursuit of rotating line targets. PMID- 1455698 TI - Sawtooth contrast sensitivity: effects of mean illuminance and low temporal frequencies. AB - Temporal contrast sensitivity was measured for mirror-image sawtooth (rapid-on and rapid-off) and sine waveforms for a 1.8 deg foveal target. In one experiment, contrast sensitivity was measured for 2-26 Hz stimuli at target mean illuminance levels of 5-1260 td. At 5 td, contrast sensitivity functions for sawtooth and sine waveforms, expressed in terms of the Fourier fundamental amplitude, are equivalent. At higher light levels, sawtooth sensitivity increasingly exceeds sine sensitivity and rapid-off (decremental) sawtooths show progressively greater sensitivity than rapid-on (incremental) sawtooths. This pattern of results was obtained for two color-normal observers and for a deuteranopic observer. In a second experiment, sawtooth and sine sensitivity was tested at 500 td with an extended low-frequency range, to 0.5 Hz. Rapid-off and rapid-on sensitivities declined only slightly at low temporal frequencies in contrast with sine sensitivity. To interpret our data, we evaluate two single-pathway models (last stage asymmetric detector and compressive response-intensity non-linearity) and a dual-pathway model in which incremental and decremental waveforms are detected by separate ON and OFF visual mechanisms. PMID- 1455699 TI - Age-dependent intensity-difference thresholds in pigeons. AB - Recent studies have reported age-related deficits in visual acuity and changes in retinal morphology in pigeons. The experiment reported here was designed to determine the effects of age on intensity difference thresholds in pigeons. Six subjects, age 2-17 yr, were trained to discriminate between two stimuli that differed in luminance. When this training was complete, the subjects were presented with a series of stimulus comparisons ranging from 0.08 to 0.43 log unit. Threshold was calculated by determining the luminance difference that corresponded to 75% correct. These data were pooled with 56 intensity-difference thresholds that had been collected from pigeons of various ages over a 20 yr period using the same procedure. A regression analysis that was performed on the pooled data set gave the result b = 0.0038, d.f. = 61 P < 0.05, r2 = 0.066 which indicates that age accounted for approx. 7% of the variance in intensity difference threshold. This finding, although statistically significant, indicates that as pigeons age their ability to perform this type of non-spatial discrimination task is not greatly impaired. This finding suggests that deficits associated with a spatial visual task in pigeons, such as visual acuity, are task specific and are not due to a global performance deficit. PMID- 1455700 TI - Isoluminant stimuli may not expose the full contribution of color to visual functioning: spatial contrast sensitivity measurements indicate interaction between color and luminance processing. AB - Visual performance is greatly impaired when tested with heterochromatic isoluminant stimuli. It is thus concluded that the chromatic system contribution to many visual tasks is limited. We suggest that unless color and luminance are shown to be processed independently, such experiments do not demonstrate shortcomings of the chromatic system but rather the inadequacy of using isoluminant stimuli for isolating that system. We hypothesize that color vision has evolved not only to encode color per se but also to enhance luminance-based visual processing, so that for color information to be fully effective, luminance as well as chromatic variations should be present in the stimulus. The hypothesis was tested by studying the contribution of color to spatial vision. The human contrast sensitivity function (CSF) was studied using luminance, isoluminance (color) and combined luminance/color sinusoidal gratings. It is found that luminance contrast sensitivity is enhanced when luminance contrast is accompanied by color contrast and vice versa. The nature of the interaction is best described by an additive single analyzer model. Color opponent cells which respond to both chromatic and achromatic stimuli may be identified as the analyzer. PMID- 1455701 TI - Moving two-dimensional patterns can capture the perceived directions of lower or higher spatial frequency gratings. AB - Coherent plaid motion is produced by superimposing two one-dimensional gratings of the same spatial frequency moving +/- 60 degrees from the intersection-of constraints (IOC) resultant direction. These moving plaids were found to change the perceived direction of a third one-dimensional grating, either 6-fold lower or higher in spatial frequency, from traveling in one of the plaid's component direction to the IOC resultant direction. We describe this phenomenon as coherence capture. Coherence capture was found to be effective between plaids with 0.5, 1.0, and 1.5 c/deg components and gratings of 3.0, 6.0 and 9.0 c/deg respectively. It was also found to be effective between plaids with 3.0 c/deg components and gratings of 0.5 c/deg. However, coherence capture between higher spatial frequency plaids and lower spatial frequency gratings became less effective when the component spatial frequencies of the plaid increased. PMID- 1455702 TI - The optics of the spherical fish lens. AB - The optical design of the fish eye is particularly simple because immersion renders the cornea optically ineffective and the lens is nearly spherical in shape. Measurements have shown that an approximately parabolic gradient of refractive index exists within the lens. If full internal and external spherical symmetry of the lens applies, the geometrical-optical behaviour of the lens is then a function only of the refractive index of the surrounding medium, that of the lens core and cortex, and of the form of the index gradient. The theoretical optical performance of models of the spherical fish lens is calculated by means of the ray-tracing program Drishti as a basis for understanding the optical design of real fish and aquatic eyes. Models based on the gradients proposed by earlier workers are shown to be unable to predict reported spherical aberration and image quality. A model of the fish lens with a polynomial gradient is proposed that yields spherical aberration, image quality and chromatic aberration similar to that reported for the fish. PMID- 1455703 TI - Robustness of perception of heading from optic flow. AB - Heading discrimination in optic flow stimuli was investigated in 5 humans. Flow patterns consisted of a computer generated motion sequence which showed a mixture of randomly moving and coherently-moving points. The motion of the coherently moving fiducial points was completely determined by the changing position of the observer's simulated vantage point. Ego-rotation as well as ego-translation was simulated. Noise and fiducial points were confined to the ground plane in most experiments. In one experiment the points formed a cloud with no visible horizon. The results indicate that heading perception is robust against degradation of the flow-field by the presence of noise or by the reduction of the lifetime of the fiducial points. The results suggest that points, which move independently from the reference frame as formed by the fiducial points, are to a large extent removed from the analysis of optic flow by the visual process which derives the heading. The motion of recognizable points at infinity (like the horizon) appears to be essential for robust heading perception in the presence of ego-rotations. PMID- 1455704 TI - The effect of adaptation on the differential sensitivity of the S-cone color system. AB - This paper presents a psychophysical dissection of the S-cone color system. Experiments were guided by a skeletal model that assumed a first stage consisting of S-, M- and L-cones, and a second stage of the opponent combination of the S and L+M signals. The response of the S-cone system was isolated by measuring difference thresholds between lights that were equiluminant tritanopic confusion pairs and thus differed only in S-cone excitation. Two types of mechanisms that control sensitivity in the S-cone system were identified: (i) static mechanisms that have a restricted range and thus limit discrimination to a small range of inputs; and (ii) adaptive mechanisms that change the state of the system in response to changes in steady illumination, so that the system is sensitive to small changes from the adapting light. These mechanisms were localized by lights that stimulated the S-cone system while keeping the signal constant at either the S, the L+M, or the post-opponent stage. The response function of the static mechanism was estimated by measuring difference thresholds at judgment points other than the steady adapting light. This procedure was repeated at a number of adaptation lights to examine the properties of adaptive mechanisms. The data were consistent with an elaborated model that included identical multiplicative gain control mechanisms in the S and L+M pre-opponent branches, and a post-opponent static sigmoidal nonlinearity with different amounts of compression for positive and negative opponent inputs. PMID- 1455705 TI - The spatial localization deficit in amblyopia. AB - There have now been numerous reports of a spatial localization deficit in amblyopia but none so far have tackled (1) the relationship between the contrast sensitivity and spatial localization deficits and (2) whether the spatial localization deficit is best described in units of visual angle or in terms of the underlying filter size. These issues are germane because they lie at the very heart of our understanding of the underlying deficit in amblyopia. To answer these questions we use spatially bandpass stimuli so that we can readily compare detection and localization for the same stimuli at each of a number of spatial scales. For some amblyopes (all strabismics and a minority of anisometropes) the contrast sensitivity defect neither underlies nor covaries with the spatial localization deficit. In the majority of anisometropic amblyopes, the contrast sensitivity loss is a complete description. The spatial localization deficit in amblyopia is of two independent kinds; positional inaccuracy and positional distortion. The positional inaccuracy deficit which can occur in varying degrees in both strabismic and anisometropic amblyopia, affects all spatial scales equally and therefore is best thought of in terms of a constant fraction of the underlying filter size in the space-frequency plane. The positional distortion deficit which can also occur to varying degrees in both strabismic and anisometropic forms can not be easily understood within this metric at least for strabismics. PMID- 1455706 TI - Static roll and pitch in the monkey: shift and rotation of Listing's plane. AB - In three rhesus monkeys three-dimensional eye positions were measured with the dual search coil technique. Recordings of spontaneous eye movements were made in the light and in the dark, with the monkeys in different static roll or pitch positions. Eye positions were expressed as rotation vectors. In all static positions eye rotation vectors were confined to a plane, i.e. Listing's plane was conserved. Tilt about the roll axis shifted the plane along this axis, i.e. a constant torsional component was added to all eye positions. Tilt about the pitch axis changed the pitch angle of Listing's plane. PMID- 1455707 TI - The two-dimensional shape of spatial interaction zones in the parafovea. AB - The spatial analysis of a target may be strongly degraded by the simultaneous presentation of nearby pattern elements. The present study investigated the shape and extent of the region of interaction as a function of retinal location. The stimuli consisted of 3 collinear [symbol: see text] s which were randomly oriented up ([symbol: see text]) or down ([symbol: see text]). The task was to discriminate the orientation of the middle [symbol: see text]. The retinal locations studied were at 0, 2.5, 5 and 10 degrees, on the lower vertical meridian and on the nasal halves of both the horizontal and the 45 degrees diagonal visual field meridians. The extent of the interaction region was defined as the separation between the midpoint of two adjacent [symbol: see text] s that resulted in 75% correct discrimination. The shape of the interaction region was determined by using several orientations (horizontal, vertical, left diagonal and right diagonal) for the virtual line joining the 3. [symbol: see text] s. Our results show that the size of the interaction regions varies linearly with eccentricity as does the size of a just resolved individual [symbol: see text]. However, the size of the interaction region varies much more rapidly than does the resolution threshold for an individual [symbol: see text]. The spatial interaction zones appear to be elongated radially, so that they have an elliptical shape. The size of the major axis is about 2-3 times the size of the minor axis. The major axis is along the meridian through the central visual field (i.e. it is oriented radially) while the minor axis is oriented tangentially (i.e. isoeccentrically). PMID- 1455708 TI - An operational approach to colour constancy. AB - Colour constancy is traditionally defined as the invariance of perceived surface colours under changes in the spectral composition of the illuminant. Existing quantitative studies show that, by this definition, human subjects show poor colour constancy. A different and complementary aspect of colour constancy is considered which is concerned with the ability of a subject to attribute correctly changes in the colour appearance of a scene either to changes in reflecting properties of the surfaces that make up the scene, or to changes in the spectral composition of the illuminant. Data are presented showing that, if the changes in the appearance of a scene were sufficiently great, subjects were capable of making the required discriminations highly reliably, and without scrutiny. PMID- 1455709 TI - Mobility performance with a pixelized vision system. AB - A visual prosthesis, based on electrical stimulation of the visual cortex, has been suggested as a means for partially restoring functional vision in the blind. The prosthesis would create a pixelized visual sense consisting of punctate spots of light (phosphenes). The present study investigated the feasibility of achieving visually-guided mobility with such a visual sense. Psychophysical experiments were conducted on normally sighted human subjects, who were required to walk through a maze which included a series of obstacles, while their visual input was restricted to information from a pixelized vision simulator. Walking speed and number of body contacts with obstacles and walls were measured as a function of pixel number, pixel spacing, object minification, and field of view. The results indicate that a 25 x 25 array of pixels distributed within the foveal visual area could provide useful visually guided mobility in environments not requiring a high degree of pattern recognition. PMID- 1455710 TI - Modeling the dynamics of light adaptation: the merging of two traditions. AB - Light adaptation has been studied using both aperiodic and periodic stimuli. Two well-documented phenomena are described: the background-onset effect (from an aperiodic-stimulus tradition) and high-temporal-frequency linearity (from the periodic-stimulus tradition). These phenomena have been explained within two different theoretical frameworks. Here we briefly review those frameworks. We then show that the models developed to predict the phenomenon from one tradition cannot predict the phenomenon from the other tradition, but that the models from the two traditions can be merged into a class of models that predicts both phenomena. PMID- 1455711 TI - An analysis of the VEP to luminance modulation and of its nonlinearity. AB - Identification of the VEP luminance modulation system was carried out using a relatively long pseudorandom binary m-sequence stimulus. The complete first order cross-correlation function provides a "fingerprint" of the nonlinearity in the time domain. Volterra kernel slices up to third order are recognized in the complete first order cross-correlation function. They all lie close to the major diagonal. Higher order kernel slices are not measurable. A cascade block model (sandwich model) analysis shows the nonlinearity to be an asymmetric rectification. Luminance increase causes a stronger response than does luminance decrease. The pre-filter gain function is low-pass. The post-filter gain function is band-pass tuned near 10 Hz. Coherency spectra are used to examine the channel structure of the system. Two channels operating near 8 and 15 Hz are easily identified. Another broad channel (or possibly multiple channels) is present above 30 Hz. In many subjects, the pseudorandom stimuli allow a complete system identification to be carried out in less than 82 sec. PMID- 1455712 TI - An intensity-dependent biphasic neuron in mudpuppy retina. AB - Intracellular recordings in dark-adapted mudpuppy retinas have revealed a type of infrequently encountered cell with unusual response properties. These cells may be a subclass of horizontal cell since they are encountered at the same depth as horizontal cells and have large receptive fields and response amplitudes. However, they differ from typical horizontal cells in that they are depolarized by low intensity illumination and hyperpolarized by higher intensity illumination at all wavelengths. Both types of responses appear to be driven mainly by 572 nm cones. Both the depolarizing and hyperpolarizing responses were unaffected by APB, indicating that they are not mediated by on-center bipolar cells. PMID- 1455713 TI - Cortical neurons: isolation of contrast gain control. AB - The selectivity of cortical neurons remains invariant with contrast, even though the contrast-response function saturates. Both the invariance and the saturation might be due to a contrast-gain control mechanism. To test this hypothesis, a drifting grafting was used to measure the contrast-response function, while a counterphase grating was simultaneously presented at the null position of the receptive field (where it evokes no response at any contrast). When the contrast of the counterphase grating increased, the contrast-response function shifted primarily to the right. This result is consistent with the hypothesis that there is a fast-acting gain-control mechanism which effectively scales the input contrast by the average local contrast. PMID- 1455714 TI - On the relation between ERG waves and retinal function: inverted rod photoresponses from the frog retina. AB - In rod mass receptor photoresponses recorded across the isolated frog retina, a paradoxical cornea-positive wave may precede the response of normal polarity. We present a model which shows that the light-induced decrease in rod current can give rise to inverted or biphasic ERG signals if the distal part (tip) of the rod outer segment responds more slowly and/or less sensitively than the proximal part (base). The condition is that current entering at the tip is represented with greater weight in the ERG. The model reproduces recorded ERG waveforms well. It further predicts that if there is a light-insensitive conductance in the tip membrane, ERG photoresponses may be non-recordable although current photoresponses are only slightly reduced. The model reveals a type of complexity in the relation between mass potentials and underlying physiological processes which has not previously received attention. PMID- 1455715 TI - Color fusion and flicker fusion frequencies using tritanopic pairs. AB - We determined color fusion and flicker fusion frequencies for tritanopic color pairs, so that only short wavelength sensitive cones were modulated. The minimally distinct border (MDB) technique was used to determine tritanopic pairs for each observer. If S-cones do not contribute to the luminance channel, color fusion and flicker fusion frequencies should be equal, because the achromatic flicker perceived beyond color fusion frequency is supposed to be elicited just by the luminance channel. The results show a significant difference between color fusion and flicker fusion frequencies for all pairs and for all subjects, which suggests a contribution of S-cones to the luminance channel. However, the results also showed that the residual achromatic flicker can not be eliminated by adjusting relative luminance of two colors flickering in counter-phase. The relative luminance stayed the same as the MDB setting when residual flicker was minimized. This means that minimum flicker was obtained when L- and M-cones are temporally silenced, and suggests little or no contribution of S-cones to luminance channel. These conflicting results might be explained by phase shift between responses of S-cones and other longer-wavelength-sensitive cones. PMID- 1455716 TI - The Bezold-Brucke effect in the color vision system of the honeybee. AB - Evidence is presented that intensity dependent color shifts (Bezold-Brucke effect) occur in the color vision system of the honeybee. The evidence comes from a fit between the choices of monochromatic lights in training experiments (Menzel, R., 1981; Journal of Comparative Physiology A, 141, 389-393) and the choice percentages derived now from recently presented quantitative predictions from the color opponent coding (COC) model for the bee (Backhaus, W., 1991; Vision Research, 31, 1381-1397) for the Bezold-Brucke effect. The only open parameter in the simulations of the training experiments is an experiment type dependent factor describing the weighting of color differences (judgement values) in the choice behavior. The results show (1) that the Bezold-Brucke effect exists in the bee. The results (2) confirm the color opponent coding (COC) model which was developed to describe the physiological components of the color vision system in the bee, (3) the general psychophysical assumptions about the structure of the color space, (4) the color difference formula, and (5) the general psychophysical assumptions about the (triadic) structure of judgements as tested in color similarity experiments. PMID- 1455717 TI - On the scaling of size judgements by orientational cues. AB - Observers carried out multiple, concurrent size discriminations with a range of size standards. The task was to classify each stimulus as larger or smaller than the appropriate standard size for the set to which it belonged. The set to which each stimulus belonged was indicated by its orientation, or in different experiments, by its spatial location. Observers were able to maintain appropriate discrimination, both when there were four concurrent standards and when there were eight. Both angle and position functioned as effective cues. The size of the orientational cue appeared to make little difference to the efficiency of discrimination. However, when the relationship between standard size and orientation was random, rather than regular, performance got worse. The analogy between such discrimination and size constancy is pointed out, and the results are discussed in relation to Andrews, D. P.'s [(1964) Quarterly Journal of Experimental Psychology, 16, 104-115)] account of perceptual calibration. PMID- 1455718 TI - The precision of size constancy. AB - The precision of objective size judgments, made when target disparity changed at random from trial-to-trial, was compared to the precision of angular size judgments made under the same condition. Subjects judged incremental changes in the vertical distance separating a pair of horizontal lines. For the objective judgments (in cm), the angle subtended by the target separation decreased with increasing depth consistent with the natural geometry of physical objects. For the angular judgments (in arc min), the angular separation did not change with disparity. For separations subtending an angle < 10 arc min, objective thresholds were considerably higher than angular thresholds, indicating that size constancy does not function well at small scales. At larger scales (> 20 arc min), the Weber fractions for angular and objective thresholds were nearly equal (approximately 6%) for two of the three subjects. These same two subjects also learned to judge "objective size" when angular subtense systematically increased with increasing depth in an exact inversion of the natural relationship. Although their "anti-constancy" judgments were less precise (approximately 9%) than their constancy judgments, the fact that subjects could learn this task with little practice suggests that constancy itself may be a learned response. Angular thresholds for targets presented only in the fixation plane were significantly lower than the angular thresholds measured with random changes in disparity, showing that observers with normal stereopsis do not have direct access to information about the angle subtended at the retina. PMID- 1455719 TI - Fourier analysis of the stimuli for pattern-induced flicker colors. AB - Pattern-induced flicker colors (PIFCs) were observed and color matched in rotating discs from which higher-harmonic Fourier components in the square-wave temporal luminance functions of a conventional black-and-white Benham disc had been removed. Since both reddish-brown and blue PIFCs were visible with purely sinusoidal stimuli they cannot result from differences in temporal stimulus shape or pattern and do not provide evidence for a temporal coding theory of color. Green PIFCs differed in that they did require the presence of additional harmonics. In a second experiment the luminance means upon which the sinusoidal PIFC stimuli were imposed were varied. The results show that color is determined by the phase of the time-varying contrast between the two parts of the stimulus pattern. This points to a site proximal to the outer plexiform layer for the phase-sensitive interaction causing PIFCs. PMID- 1455720 TI - Failure of rivalry at low contrast: evidence of a suprathreshold binocular summation process. AB - Presentation of different images to the two eyes normally results in a time varying alternation between the two images (binocular rivalry). However, we find that when orthogonal gratings are viewed dichoptically at low contrast, a stable summation between the two images is perceived in the form of a dichoptic plaid. The range of perception of the dichoptic plaid depends on spatial frequency, contrast and luminance of the gratings. This phenomenon differs from the "false fusion", a fleeting summation of different images perceived only under very brief presentation of the stimuli. The observations suggest that there exists a neural process that performs a summation of dissimilar images, and that is distinct from the competitive process of suppression and binocular rivalry. PMID- 1455721 TI - Spatial scaling of vernier acuity tasks. AB - Vernier acuity thresholds for two abutting lines and for a two-dot stimulus were measured as a function of stimulus magnification at eccentricities of 0, 5, 10 and 15 deg using a spatial scaling technique in which all stimuli are simply magnified versions of each other. The advantage of such a technique is that no prior knowledge of a suitable magnification factor with which to increase the size of peripheral stimuli is required. Thresholds for the line stimulus could be successfully scaled by the application of a magnification factor with an E2 value of 1.23-1.78 deg. Further, provided that the effects of dot separation and eccentricity were dissociated, spatial scaling with an E2 value of 1.06-1.96 deg was also successful in removing eccentricity dependence for two-dot vernier thresholds. PMID- 1455722 TI - Brightness, discriminability and the "crispening effect". AB - Subjects adjusted the luminances, L, of 16 or 25 circles, all visible at the same time on a computer monitor, to make equal-interval brightness series. The background was black, white or grey. The luminance steps between adjacent circles behaved like the luminance discrimination thresholds of Whittle, P. [(1986) Vision Research, 26, 1677-1691)]. They showed a sharp minimum at the background luminance, Lb: the "Crispening Effect". They followed Weber's Law with respect to L when L was small, but with respect to delta L (= magnitude of L-Lb) near Lb. The Crispening Effect was abolished by a thin outline or a hue difference between circles and background. PMID- 1455723 TI - Spectral transmittance of the rat lens. AB - The spectral transmittance of the isolated rat lens for radiation of wavelengths from 300 to 700 nm was measured using a spectrophotometer. Transmittance decreased from 93-95% at 700 nm, to 70-80% at 400 nm, 50-60% at 360 nm, 4-18% at 320 nm, and to < 2% at 310-300 nm. These results indicate that the rat lens is remarkably transparent for UVA radiation, which has consequences for rat vision, and for interpretation of earlier studies on retinal light damage. PMID- 1455724 TI - The role of binocular vision in prehension: a kinematic analysis. AB - This study examined the contribution of binocular vision to the control of human prehension. Subjects reached out and grasped oblong blocks under conditions of either monocular or binocular vision. Kinematic analyses revealed that prehensile movements made under monocular viewing differed substantially from those performed under binocular conditions. In particular, grasping movements made under monocular viewing conditions showed longer movement times, lower peak velocities, proportionately longer deceleration phases, and smaller grip apertures than movements made under binocular viewing. In short, subjects appeared to be underestimating the distance of objects (and as a consequence, their size) under monocular viewing. It is argued that the differences in performance between the two viewing conditions were largely a reflection of differences in estimates of the target's size and distance obtained prior to movement onset. This study provides the first clear kinematic evidence that binocular vision (stereopsis and possibly vergence) makes a significant contribution to the accurate programming of prehensile movements in humans. PMID- 1455725 TI - Inhibitory interaction in a split/fusion apparent motion: lack of spatial frequency selectivity. AB - Spatial-frequency selectivity of apparent motion (AM) between isolated Gabor patches was examined under two- and three-patch conditions. In the two-patch condition, the likelihood of seeing AM between two Gabor patches was measured with varying frequency difference between the patches. In the three-patch (split/fusion) condition, the likelihood of AM between target patches of the same frequency was measured as a function of the frequency of the inhibiting patch. AM perception in the two-patch condition deteriorated with increasing frequency difference, showing symmetrical spatial-frequency selectivity. On the other hand, the inhibition of AM in the three-patch condition was frequency asymmetric; when the frequency of the inhibiting patch was higher than that of the target patches, the magnitude of inhibition decreased with increasing the frequency of the inhibiting patch. When the frequency of the inhibiting patch was lower, the magnitude of inhibition remained almost constant regardless of the frequency difference between the inhibiting and target patches. PMID- 1455726 TI - Human speed perception is contrast dependent. AB - When two parallel gratings moving at the same speed are presented simultaneously, the lower-contrast grating appears slower. This misperception is evident across a wide range of contrasts (2.5-50%) and does not appear to saturate (e.g. a 50% contrast grating appears slower than a 70% contrast grating moving at the same speed). On average, a 70% contrast grating must be slowed by 35% to match a 10% contrast grating moving at 2 degrees/sec (N = 6). Furthermore, the effect is largely independent of the absolute contrast level and is a quasi-linear function of log contrast ratio. A preliminary parametric study shows that, although spatial frequency has little effect, relative orientation is important. Finally, the misperception of relative speed appears lessened when the stimuli to be matched are presented sequentially. PMID- 1455727 TI - Redness from short-wavelength-sensitive cones does not induce greenness. AB - According to opponent-colors theory, a reddish surround induces greenness in a central test field. Color-appearance measurements verify this with a long wavelength reddish surround (660 nm) but not with a short-wavelength reddish surround (440 nm). Surprisingly, a short-wavelength reddish surround shifts the appearance of a test toward redness. Four possible explanations are: (1) stray light from the short-wavelength reddish surround falls in the test area; (2) receptoral sensitivity changes overwhelm induced greenness from the surround; (3) a neural process of assimilation, rather than contrast, to the surrounding light; and (4) short-wavelength-sensitive (S) cones do not contribute to induced redness/greenness. Chromatic cancellation experiments confirm the fourth explanation. There was no change in induced redness/greenness when quantal absorption by only S cones in the surround was varied by 30-fold (using tritanopic metamers), even though varying stimulation of S cones strongly affected the color appearance of the surround. The redness induced by a short wavelength surround is accounted for by opponent chromatic induction mediated by only middle- and long-wavelength-sensitive cones. PMID- 1455728 TI - The development of vernier acuity in human infants. AB - Vernier acuity, i.e. the detection of a small misalignment between lines, is about one order of magnitude finer than the resolution of periodic gratings in adult humans. This hyperacuity is generally attributed to cortical mechanisms, and the time-course of its development seems to differ from the development of grating resolution that probably is limited by retinal factors. We investigated 271 human infants and children between 2 months and 8 yr of age with essentially identical stimuli and experimental procedures. Vernier thresholds for Vernier targets were compared to grating resolution. The preferential looking experiments led to the following results: (i) Vernier acuity starts below grating resolution. (ii) Like grating resolution, Vernier acuity develops gradually, but more rapidly and longer; at the age of 5 yr performance becomes comparable to that of adults. (iii) Flanking borders without offset, added to the Vernier targets at various distances, did not affect thresholds consistently across distances and age groups. PMID- 1455729 TI - A multi-channel approach to brightness coding. AB - A model of brightness coding is presented which is shown to predict the appearance of a number of classical brightness phenomena. The model is known as MIDAAS which stands for Multiple Independent Descriptions Averaged Across Scale. In common with many other approaches to brightness perception MIDAAS imputes to local feature detectors a central role in the computation of brightness. It also explicitly recognises the crucial importance to brightness perception of feature detectors operating at different spatial scales. The unique and definitive feature of the model however is the supposition that each scale of spatial filtering operates as if to generate its own description of the pattern of brightness relationships in the image. The final percept is then provided by the composite of those individual brightness descriptions. It is shown that MIDAAS provides a good account of a variety of Mach band phenomena, the conditions under which the Missing Fundamental illusion is observed, the effect of occluding bars on the apparent contrast of step edges, the Chevreul illusion, simultaneous brightness contrast and the non-linear appearance of high contrast sinusoidal gratings. The advantages of MIDAAS over other approaches to brightness perception is discussed, as well as its current limitations. PMID- 1455730 TI - The eyespot of Euglena gracilis: a microspectrophotometric study. AB - The eyespots in cells of streptomycin-bleached strains and of dark-grown cultures of Euglena gracilis, were examined by means of fluorescence microscopy and microspectrophotometry. When viewed with light in the region of 380-500 nm, the stigma appeared as a dark spot. Adjacent to this was a second spot, not seen with white light, but which was seen to fluoresce when excited with radiation at 370 +/- 20 nm. This fluorescence proved to be polarized in contrast to other fluorescing bodies in the cell. The absorption curves, obtained by microspectrophotometry of individual eyespots, were found to consist of two spectral maxima, an A-band in the blue and a B-band in the green. Unlike the A band, the B-band provided evidence of originating from an anisotropic structure. Relating these data to literature findings, we conclude that the B-band is the absorbance of a pigment in the quasi-crystalline paraflagellar body and the A band perhaps a pigment in the orange-red stigma. The spectrum of the B-band does not appear to be that of a flavoprotein or of a free carotenoid but its resemblance to the spectrum of rhodopsin is significant in relation to published data for the Chlamydomonas eyespot that suggests the presence of a rhodopsin-like pigment as the photosensitive system responsible for phototaxis in this alga. PMID- 1455731 TI - The eyespot of Chlamydomonas reinhardtii: a comparative microspectrophotometric study. AB - The eyespot of Chlamydomonas reinhardtii is believed to utilize a rhodopsin-like pigment in its responses to light. This paper examines its eyespot by means of microspectrophotometry with the finding of an absorption spectrum with two bands, an A-band in the blue, and a B-band in the green. This spectrum is identical to that previously recorded from the eyespot of Euglena gracilis. As with Euglena the B-band was found to have dichroic character and its spectrum was similar to the absorption curve of rhodopsin. This A-B-spectrum was always recorded from a single granule in each cell. It is concluded that both E. gracilis and C. reinhardtii may utilize a rhodopsin-like pigment as the photopigment associated with the eyespot response to light. In both these algae a few particles in each cell were found whose spectra consisted of two other bands, C and D, blue- and red-shifted, respectively, relative to the eyespot A-B-bands. There is some reason to believe that the C-D-granules may also be involved in certain light controlled activities of the cells. PMID- 1455732 TI - Retinal perivascular astroglia: an immunoperoxidase study. AB - Different morphological types of retinal perivascular astrocytes have been studied in wholemount preparations of rabbit retina. Astrocytes were immunohistochemically demonstrated using glial fibrillary acidic protein monoclonal antibodies (GFAP clone GA-5). Three types of perivascular astrocytes were found. Type I has an ovoid perikaryon which gives rise to numerous hair-like processes, and it shows strong GFAP reactivity; these cells are associated with medium-size vessels and capillaries. Type II is star-shaped and its spherical perikaryon has a basal cone with four to ten small, protruding, radial processes; these astrocytes show high GFAP reactivity and are located on larger and medium size vessels. Type III astrocytes show the classic, star-shaped morphology in which processes emerge directly from the perikaryon which lacks a basal cone. However, different from Types I and II, Types III astrocytes show low GFAP reactivity and are positioned between capillaries. These cells are the only ones that can contact other astrocytes of the same type to form a network. PMID- 1455733 TI - Development of temporal properties of pattern electroretinogram and visual evoked potentials in infants. AB - The postnatal development of the temporal properties of the responses to pattern contrast reversal has been studied by recording simultaneously the pattern electroretinogram (PERG) and visual evoked potentials (PVEP) in infants 3-22 weeks old. The stimulus grating (0.5 c/deg) was either reversed in contrast sinusoidally at frequencies 4-10.5 Hz to study the temporal frequency function of steady-state responses, or square-wave reversed at 1 Hz to evaluate the peak latency of transient responses. Developmental changes of the shape and bandwidth of the temporal frequency function of both PERG and PVEP occur post-natally and are particularly pronounced between 13 and 20 weeks from birth, possibly indicating deferred maturation of classes of retinal and central neurons with higher temporal resolution. The peak latency of the PERG decreases during the age period tested to approach adult values towards the end of the fifth month. The rate of decrease of the peak latency of the PERG differs from that of the PVEP, indicating that post-retinal factors contribute largely to the maturation of the latter, especially in the earliest life period. PMID- 1455734 TI - Color perception within a chromatic context: changes in red/green equilibria caused by noncontiguous light. AB - We measured changes in the color appearance of one light caused by another light presented in a well-separated region. Observers viewed a 1 degrees test field superimposed on a 3 degrees, 540 or 660 nm adapting field (32 or 320 td). The change in appearance due to noncontiguous light was determined by surrounding the 3 degrees adapting field with a continguous 3 degrees i.d., 5 degrees o.d. ring of either 32 or 320 td. The ring was 540, 660 nm or achromatic (tungsten-halogen "white"). The test was an admixture of 549 and 660 nm light, and varied from 6 to 1000 td. The observer adjusted the ratio of 549 to 660 nm test light so the test appeared neither reddish nor greenish. A 540 or 660 nm ring had a chromatic inducing effect on the small test that mimicked a simple surround contiguous with the test. Results with an achromatic ring were more complex: an isolated achromatic ring (no adapting field present) had virtually no effect on the color appearance of the test, but the same achromatic ring surrounding a chromatic adapting field shifted the test toward the color appearance of the adapting light (e.g. introducing a "white" ring surrounding a "green" adapting field shifted the test toward greenness). A thin pencil-width band of "white" light superimposed on a larger 5 degrees adapting field had an effect similar to a "white" 3-5 degrees ring. These results demonstrate (1) strong effects of the remote noncontiguous lights and (2) that the change in color appearance they cause is not a simple function of only the light in the noncontinguous region. The change depends on other lights in view. The visual processes revealed in these experiments are considered in terms of inferred illumination and surface reflectances of objects in natural scenes. PMID- 1455735 TI - Positive motion after-effect induced by bandpass-filtered random-dot kinematograms. AB - Using spatially filtered random-dot kinematograms (RDK) with a 1 octave bandwidth, the duration and direction of motion aftereffect (MAE) were measured while varying step displacement, and the results were compared to those for motion direction discrimination. We found that MAE and motion discrimination show quite different dependencies on displacement. At displacements around 0.5 cycles of the lowest frequency, while motion discrimination was still almost perfect, normal MAE vanished and MAE in the same direction as that of the adapting stimuli, which we name "positive MAE", was observed. Similar results were obtained for both 1- and 2-dimensional filtered patterns. A theoretical examination based on the Fourier components of the stimuli showed that the displacement dependency of MAE is predictable in terms of adaptation of first order detectors, but that of motion discrimination is not. The present results indicate that direction perception and MAE for bandpass RDKs are mediated at least partially by separate mechanisms, and that direction perception at larger displacements is mediated by the second-order mechanism which detects movement of contrast modulation in the image. PMID- 1455736 TI - Calibration of three-dimensional eye position using search coil signals in the rhesus monkey. AB - A procedure is described to calibrate three-dimensional eye position with a dual search coil implant in rhesus monkeys using a two-field magnetic system. The method allows one to determine the sensitivity of the search coils taking into account the presence of d.c. offset voltages. The orientation of the implant on the eye relative to a space-fixed reference frame is computed using fixations of targets arranged vertically. The critical steps of the procedure are discussed and documented by experimental data. PMID- 1455737 TI - Dissociation of orientation discrimination from form detection for motion-defined bars and luminance-defined bars: effects of dot lifetime and presentation duration. AB - A stationary bar-shaped area that was perfectly camouflaged within a dot pattern was rendered visible by moving the dots inside and outside the bar at equal and opposite speeds. Orientation discrimination for this motion-defined (MD) bar was compared with orientation discrimination for a luminance-defined (LD) bar created by switching off all dots outside the bar. The best values of orientation discrimination threshold were similar for MD and LD bars at long presentation durations and long dot lifetimes. But, as presentation duration or dot lifetime was reduced below 1.0 sec, orientation discrimination threshold for MD bars increased at an accelerating rate, while discrimination for LD bars was comparatively unaffected. However, these effects of presentation duration and dot lifetime were largely due to changes in bar visibility. When bar visibility was normalised relative to the relevant bar detection threshold, the effect of presentation duration upon orientation discrimination was abolished for both MD and LD bars, and the effect of dot lifetime was abolished or even reversed. These observations dissociate detection and discrimination for MD and LD form. We suggest that orientation discrimination for MD and LD bars is determined by opponent-orientation mechanisms whose performance is not directly affected by presentation duration, nor degraded by reducing dot lifetime. PMID- 1455738 TI - Depth discrimination of a line is improved by adding other nearby lines. AB - Depth discrimination thresholds are shown to be lowered by up to a factor of 10 when a few reference lines are added to a stimulus containing a single isolated test line. Four reference lines are better than two, which are better than one, and the improvement in performance is greater when the test line lies between the two reference lines in depth. Stereoacuity for the relative depth of a target line, relative to other nearby reference lines, is shown to be insensitive to changes of disparity of the whole pattern of up to about +/- 5 arc min and is only weakly sensitive to larger displacements of up to +/- 10 arc min. PMID- 1455739 TI - The conjugacy of human saccadic eye movements. AB - Binocular measurements of instantaneous velocity vectors in normal human subjects during saccades showed: (1) considerable trial to trial variation in peak velocity, saccade duration, and saccade curvature despite saccade accuracy; (2) variations in one eye were mirrored by similar variations in the other eye, with a high positive correlation. The high correlation between the peak velocities suggest that saccades in the two eyes are driven by a common saccade generator. Assuming that a local feedback loop guides saccades, the high correlation between saccade durations and between saccade curvatures suggests that both eyes are guided by common feedback. If so, monocular adaptation must occur downstream from the saccade generator. PMID- 1455740 TI - Disparity tuning in mechanisms of human stereopsis. AB - The change in sensitivity across some stimulus dimension which follows adaptation to a particular stimulus can reveal a great deal about the tuning characteristics of underlying sensory/perceptual mechanisms. In this study, a psychophysical adaptation paradigm was employed to characterize the disparity tuning of perceptual mechanisms involved in stereopsis. The stimulus was a dynamic random dot stereogram (DRDS) portraying a surface which varied in interocular correlation (IOC) and retinal disparity. Adaptation to a fully correlated DRDS surface produced an elevation in IOC threshold over a relatively narrow range of disparities, with maximum effect at the disparity of the adapting stimulus. The width of these disparity tuning functions varied from 5 arc min for adaptation at the horopter to 20 arc min for adaptation at 20 arc min disparity. Frequently, IOC sensitivity was enhanced for disparities on either side of the adapted disparity, suggesting that an opponent center-surround organization operates at an early level of disparity processing. A model of underlying channel structure consistent with these data is presented. PMID- 1455741 TI - Lateral interactions within color mechanisms in simultaneous induced contrast. AB - The perceived color of a region of visual space is a function not only of the spectral composition of the light incident from it, but also depends on the light incident from surrounding regions. The color contrast induced into a region is a result of lateral interactions between neural mechanisms. These interactions were studied by measuring the induced effect of circularly symmetric spatial sine waves on a circular central test region. The phase of the surrounding sine-waves was changed uniformly in time, inducing a modulation in the appearance of the test. Observers adjusted the amplitude of real sinusoidal modulation in the test in order to null the induced modulation, and the nulling modulation was used as a measure of the induced effect. Spatial additivity was tested by using pairs of sine-waves of distinct spatial frequencies. The results showed that brightness induction can be characterized as a linear spatial process, i.e. the effects of parts of the surround at different distances from the test are summed, after the effect of each part is weighted by a negative exponential as a function of distance from the test. The magnitude of pure chromatic induction, however, is a result of nonlinear spatial interactions. Thus, these results have implications for the connections between visual mechanisms that process brightness and chromatic contrast. PMID- 1455742 TI - Spectral sensitivities for illusory contour perception: a manifold linkage of chromatic and achromatic cues with the generation of contours. AB - Using colored inducing patterns presented as increments upon a white uniform background, the increment thresholds needed for illusory contour perception were measured as a function of the wavelength of inducing pattern. The spectral sensitivity functions were obtained with varying adaptation level and stimulus configuration, high and low background illumination, and line-based and figure based inducing patterns. The results showed a distinctive feature between the line-based and the figure-based illusory contours. The sensitivity functions for the line-based illusory contours showed the characteristics of non-opponent mechanisms and they were shape invariant with background intensity and spatial variables. On the other hand, the sensitivity functions for the figure-based illusory contours showed non-opponent nature for low background illumination but opponent nature for high background illumination. It is suggested that the generation of illusory contours involves concurrent processing of different cues of luminance and color, and that photopic adaptation level and stimulus configuration control the degree of the contributions of chromatic and achromatic mechanisms to contour formation. PMID- 1455743 TI - The discrimination of blur in peripheral coloured borders. AB - Our interest is in measuring the threshold for blur, for long borders at well defined retinal eccentricities between large fields of colour. Our method is to precisely match a centrally fixated sharp-edged disk of one colour against a surround of another, using the minimum distinct border criterion. We then measure the amount of added Gaussian blur that makes the sharp step-edged border just noticeably different. The selected colours are small fixed chromatic deviations of 500 msec duration from an adaptive low photopic or mesopic white. The effects of retinal eccentricity are striking. Blur thresholds are large for yellow-blue borders centrally (at 1.25 degrees eccentricity) and extremely large for red green borders peripherally (at 20 degrees). Blur thresholds are generally larger for isoluminous chromatic borders than for a low contrast achromatic border. Accurate Rovamo-Virsu M-scaling is limited to photopic achromatic borders. PMID- 1455744 TI - Psychophysical and saccadic information about direction for briefly presented visual targets. AB - For saccades, the difference between desired and actual eye movement (constant error), as well as the variability in amplitude on repeated trials (variable error), presumably represent a combination of errors in processing target position (sensory error) and errors in execution (motor error). To examine whether the saccadic system uses the same information about target position as visual perception, subjects made saccades to and psychophysical judgments about the location of targets presented for 17-200 msec. Mean saccadic amplitude markedly decreased and inter-trial variability increased when saccadic targets were presented briefly and followed by a spatial mask. Judged target position (from psychophysical vernier and bisection tasks) also shifted to lesser eccentricities and was more variable. Although qualitatively alike, changes with duration in saccadic constant errors were larger than could be accounted for by the psychophysical results, suggesting similar but separate processing of position information for the saccadic and perceptual systems. Differences in the sizes of collicular receptive fields that preferentially respond to targets at short and long durations can account qualitatively for the observed changes in saccadic amplitude as well as the common occurrence of saccadic undershoots. PMID- 1455745 TI - Scotopic spectral sensitivity of phakic and aphakic observers extending into the near ultraviolet. AB - Despite interest in ultraviolet (UV) damage and UV vision in lower vertebrates, there are few recent publications on human UV sensitivity. We obtained dark adapted spectra from 4 aphakic and 5 normal eyes at 8.8 degrees off-fovea using the staircase method. Our measurements extended from 314.5 nm, near the limit imposed by corneal UV absorbance, to 650 nm. Phakic and aphakic sensitivities resembled the traditional rod spectrum at long wavelengths with a peak around 500 nm. However, aphakic subjects were much more sensitive than phakic observers below 420 nm. From phakic volunteers ranging in age from 22 to 43 we deduced lens absorbance which depressed sensitivity at 350 nm by approx. 4 log units (n = 7 phakic runs on 5 eyes, average age = 30) as expected. We show a maximum lens absorbance at 355-360 nm and a UV window in the lens absorbance at 315 nm consistent with data on optical density of human lenses. PMID- 1455746 TI - Heterochromatic Fusion Nystagmus: its use in estimating chromatic equiluminance in humans and monkeys. AB - The use of chromatic patterns that are equated for luminance has become increasingly popular in psychophysical and neurophysiological studies of visual processing. The currently available techniques for equating different colors for brightness rely upon human reports of perceptual events that are reduced at some luminance ratio. We report here the results of a study using a technique we have recently developed that produces a vivid and compelling motion percept only at isoluminance. That is, unlike previous methods, this technique relies upon a perceptual event (motion) that actually becomes more salient at isoluminance. We also observed that the optokinesis generated by the moving pattern mirrors the perceptual reports at all luminance ratios. If used in this manner, the technique can provide an estimate of chromatic isoluminance in a variety of species and can be used to corroborate a human subject's perceptual experience. PMID- 1455747 TI - Spatiotemporal factors in infant position sensitivity: single bar stimuli. AB - The ability of 3-month-old human infants to detect the presence of spatial misalignments in single-bar stimuli was investigated in a series of spatiotemporal stimulus manipulations. Both discrete and sinusoidal positional offsets, either stationary or temporally modulated, were presented using the forced-choice preferential looking technique. When discrete offsets were presented in alteration with the absence of offsets, thresholds were a factor of two worse than previous estimates of infant vernier acuity using grating stimuli. However, when offsets (discrete or sinusoidal) were presented in continuous motion, mean threshold was 22-24 arcmin, comparable to previous estimates using gratings with moving discrete offsets. For stimuli containing continuous motion, lowering velocity reduced infants' positional sensitivity. However, when either velocity or temporal frequency was held constant, the most important determinant of positional sensitivity was the sharpness of the offsets. The results from the temporally-modulated stimuli suggest that a simple local flicker mechanism cannot account for sensitivity when continuous motion is used in the stimulus; rather, a local motion mechanism may govern sensitivity in these conditions. We characterize this mechanism as one of "local motion" because it does have a position-sensitive component. The two stationary stimulus conditions in the present study indicate that infants can use a position-sensitive mechanism when no temporal modulation is present. PMID- 1455748 TI - Lightness induction in the S-cone pathway. AB - Lightness induction is classically regarded as a contrast phenomenon limited to pathways which process luminance information. To determine if lightness induction can also occur in the chromatic domain, this phenomenon was studied with stimuli visible only to the short wavelength sensitive (S)-cones which have post receptoral connections limited to chromatic pathways. The lightness of an object visible only to S-cones was found to be dependent on the relative intensity of its background in a manner similar to achromatic, luminance stimuli. Less intense (dark) backgrounds made the object appear lighter, while more intense (light) backgrounds made the same object appear darker. These results indicate a commonality among lightness induction effect in the processing of chromatic and luminance information. PMID- 1455749 TI - Absence of pupil response to blur-driven accommodation. AB - The drive to the pupil constriction associated with near fixation has generally been attributed to accommodation with convergence and fusional convergence having secondary roles. However, our previous investigations have shown that significant changes in accommodation can take place without concomitant pupil response. To investigate further, the present study recorded pupil and accommodation responses to a blur-only accommodative stimulus using a target moved sinusoidally at a range of temporal frequencies. Care was taken to minimise target size change and apparent lateral or vertical target displacement. Results show that pupil response could be very much reduced or absent irrespective of stimulus temporal frequency and despite maintained accommodation response. The results suggest that blur-driven accommodation alone is not sufficient to drive pupil near response and that the presence of cues such as size change and lateral or vertical displacement of an approaching object may be necessary to elicit a response. PMID- 1455750 TI - A square root law for adaptation to contrast? AB - Several characteristic of aftereffects (especially the motion aftereffect) depend upon the square root of the time spent adapting. The same parameters are here examined for the contrast threshold elevation aftereffect. The time taken to recover is shown to be well predicted by root adaptation time (beyond a minimum duration), but the amount of threshold elevation, the rate of recovery and the integrated recovery phase cannot be so predicted. PMID- 1455751 TI - The relation between the velocity of visual motion and the reaction time to motion onset and offset. PMID- 1455752 TI - The contributions of figure and ground textures to segmentation. AB - Several models of texture segmentation use spatial gradients in the activity of early filters to locate texture boundaries. The models assume that these filters are identical to those involved in the detection and discrimination of near threshold patterns. The models differ in how activity gradients from different types of filters are combined. We examined this question by measuring the respective contributions of a figure and a ground texture to segmentation. Vertical and horizontal line segments were used to construct two perfectly discriminable textures and these textures were used to construct four types of displays. Each display contained an obliquely oriented figure, but the displays differed in the way this figure was defined. Displays consisted of either (1) a horizontally textured figure on a blank background, (2) a blank figure on a vertically textured background, (3) a horizontally textured figure on a vertically textured background or (4) a figure with a mixed texture (50% vertical lines, 50% horizontal lines) on a blank background. In a two-alternative forced choice experiment, observers were asked to judge the figure's orientation (right or left oblique), and the contrast of the textures was varied across trials. The resulting psychometric functions for segmentation were very similar for the four types of displays, suggesting ways in which a simple model of segmentation should be modified. PMID- 1455753 TI - [How should we implement the basic principles of treatment of type 2 diabetes mellitus from the aspect of the hormono-metabolic syndrome X (5H)?]. AB - The authors summarize the principles of the therapeutic approach to the 5H syndrome [1. hyperinsulinism, 2. hyperglycaemia (NIDDM), 3. hyperlipoproteinaemia (obesity), 4. hypertension, 5. hirsutism], in particular its two components, i.e. NIDDM and arterial hypertension. The authors found that early treatment of hyperinsulinism, e.g. already in the stage of impaired glucose tolerance or NIDDM with oral antidiabetics, their disproportionate increase with regard to the blood sugar level and glycosylated haemoglobin without making "hygienic" provisions (radical weight reduction; increased physical activity to the maximum possible individual level; energy restricted diet in particular as regards carbohydrates and fat) does not prevent progression of the components of the 5H syndrome to the clinical stage. In treatment of arterial hypertension associated with 5H syndrome non-selective beta-blockers and thiazide diuretics are unsuitable because they worsen the HPLP and enhance insulin resistance. Suitable preparations are combinations of ACE-inhibitors, calcium antagonists, selective beta-blockers in particular with ISA and beta-blockers with a partial selective sympathomimetic activity (devalol and celiprolol). Hygienic provisions must be started in childhood, or when hyperinsulinism is detected. PMID- 1455754 TI - [Abdominal ultrasonography]. AB - The author characterizes ultrasonography as a modern diagnostic imaging method. The main attention is drawn to abdominal ultrasonography, especially to its indications and differential diagnostics. The author evaluates critically the present state and further foreseen development of this method. Finally he makes a statement on the question of safety. PMID- 1455755 TI - [Emergency states in internal medicine--diagnostic contribution of emergency abdominal ultrasonography]. AB - The authors analyzed the activities of the sonographic laboratory during four consecutive months. During this period 896 patients were examined by ultrasonography and 119 of them (13.3%) for urgently indicated ultrasonography. The authors present a detailed evaluation of results in these 119 examined patients, in particular from the aspect of yield and asset of the method, affection of different organs, agreement of clinical and sonographic diagnoses and comparison with some other examination methods. Urgent ultrasonography is recommended as a very useful method, in particular as regards diagnostic yield which makes it possible to establish the diagnosis quickly and thus to start appropriate treatment early and to reduce thus the period spent by the patient in hospital. The method is useful also in serious cases and in some conditions which threaten the patient's life, as it can help early indication of surgery. PMID- 1455756 TI - [Monitoring immunosuppression after kidney transplantation. I. Study of cellular reactions to antigenic stimulus in a skin abrasion]. AB - In 20 patients the authors performed in the course of 6-8 weeks following renal transplantation a total of 74 examinations of the cellular reaction to an antigenic stimulus. In 68 instances (91.9%) agreement with the clinical picture was recorded, while in 6 patients (8.1%) the interpretation of the cytological impression did not correspond to the clinical course. In four instances activation of lymphocytes was found, i.e. possible risk of rejection which however was not confirmed. In two instances however incipient rejection was not detected. PMID- 1455758 TI - [Disorders of lipid metabolism in type 2 diabetics]. AB - The authors investigated the incidence of different disorders of the lipid metabolism and their age dependence in a group of 67 patients with type 2 diabetes hospitalized at the First Medical Clinic in Kosice. Some disorder of the lipid metabolism was recorded in 67% of the patients. The most frequently encountered disorder was hypertriglyceridaemia (21%). Hypercholesterolaemia was recorded in 16%, combined hyperlipidaemia in 18% and hypoalphalipoproteinaemia in 12% of the patients. Patients with diabetic nephropathy had significantly elevated mean triglyceride levels and reduced HDL-cholesterol levels, as compared with patients without nephropathy. In diabetic women a significantly higher incidence of combined hyperlipidaemias was recorded, as compared with men and the mean total cholesterol and triglyceride levels were also significantly higher in women with type 2 diabetes. PMID- 1455757 TI - [Monitoring immunosuppression after kidney transplantation. II. Evaluation of simultaneous monitoring of CD4+ lymphocytes and the cytological reaction to standard antigenic stimulation]. AB - Monitoring of patients after renal transplantations by the concurrent follow up of absolute values of CD4+ lymphocytes and the cytological reaction to an antigenic stimulation in a skin abrasion reflects the actual immune state of patients and is an asset in the comprehensive diagnosis of rejection activity against the transplant in the early period (6-8 weeks) after transplantation. It can contribute also to the signalling of developing rejection activity against the graft, before the onset of the fully developed clinical picture of rejection, when it is possible by early anti-rejection therapy to prevent the functional impairment of the renal graft. PMID- 1455759 TI - The effect of Hylak drops on symptomatology in persons with irritable bowel syndrome. AB - The authors present an account on the therapeutic effect of Hylak drops of Merckle Co. in patients with irritable bowel syndrome. They assume that in the pathophysiological mechanism of the disease an important part is played by intestinal dysmicrobia. After two weeks' administration Hylak, 3 x 40 drops, they recorded in 20 patients with the exception of one female patient (where ex post lactose intolerance was revealed which is a contraindication of this treatment), partial or complete regression of subjective complaints in particular as regards intestinal discomfort and the number of imperative bowel movements. As to objective indicators, they proved changes in the pH of faeces and qualitative as well as quantitative changes of the microbial spectrum in faeces. PMID- 1455760 TI - [Immunologic indicators in ascites]. AB - The authors investigated specific and non-specific immunological parameters in malignant, cirrhotic, cardial and nephrogenic ascites. At the same time bacteriological and cytological examinations of ascites were made. In the submitted paper the authors compare, using statistical methods, immunological parameters of ascites in different patient groups and pay attention to their relationship with positive bacteriological and cytological findings in ascites. The authors recorded the largest number of positive bacteriological cultivation in cirrhotic and malignant ascites which correlates with lower values of some non specific immunological parameters in ascites. PMID- 1455761 TI - [Secondary osteopenia. Iatrogenic causes of osteopenia]. AB - The author investigated during the past 17 years 595 patients with iatrogenic damage of bone mineralization, incl. 302 patients where the disorder developed after drugs and 293 where osteopenia developed after surgery. In demineralizations after the use of drugs in the first place corticoids participate, to a smaller extent non-thiazide diuretics and antiepileptic drugs. The largest ratio of operations causing demineralization is formed by ovariectomies, in particular if performed before the menopause, followed by gastric surgery, operations of the gallbladder, small intestine and strumectomy. Finally the author emphasizes the necessity to know iatrogenic bone damage, its early diagnosis and prevention. PMID- 1455762 TI - [Bronchial asthma. Pathogenesis and clinical aspects]. AB - Asthma bronchiale (a.b.) is defined as paroxysmal or permanent, partly or completely reversible dyspnoea due to a bronchospasm resulting from pathological hyperreactivity of the bronchial system. In the pathogenesis participate allergic, immuno-infiltrative and genetic factors, irritating substances (environment) and infectious. The allergic constituent acts via sensitization and allergization of the mast cell, to its degranulation with release of mediators (histamine, serotonin, leukotrienes, thromboxane, PAF) with subsequent bronchoconstriction and production of viscous mucus. As to adrenergic factors, a block of beta-adrenergic receptors and reduced adrenal function is involved. As to non-adrenergic factors an increased sensitivity of the parasympathetic--vagus is involved which conditions bronchoconstriction and hyperkrinia. From the clinical aspect extrinsic (atopic) and intrinsic (cryptogenic) asthma bronchiale can be differentiated. The former is encountered more frequently in childhood and adolescence, in subjects with a positive family-history, high IgE and positive skin tests and a known allergen. The latter type of a.b. is found in adolescence, in subjects with a negative family-history, with eosinophilia; it is conditioned by infection (e.g. chronic bronchitis), strain, cold and takes a dangerous course (aspirin). As to the course, attacks of a.b. are involved with a symptom-free interval (extrinsic a.) easily controlled by treatment. Then there is the chronic form with a variable course and the necessity of permanent treatment. Status asthmaticus is in recent years with increasing frequency the cause of death and thus calls for maximal treatment. It is the third most serious form of a.b. Assessment of arterial blood gases is very important as a check of treatment as well as from the prognostic aspect (cross-over intubation). From the differential diagnostic aspect we must consider the asthmoid component in chronic bronchitis, pulmonary embolism, left-sided cardiac failure, tracheal or bronchial compression by an aortal aneurysm, tumour. The differential diagnosis is not always easy. PMID- 1455763 TI - [Self-treatment and self-monitoring in patients with bronchial asthma]. AB - Regular assessment of the peak expiratory flow (PEF), which after proper instruction, the patient can do himself is important for evaluation of the activity of bronchial asthma. It is, however, essential to assess the optimal PEF values of every individual. For control of self-treatment it is important to know the daily variations of PEF and the degree of reversibility of bronchospasm after inhalation of a beta 2-adrenergic substance. Inadequate reversibility of bronchial obstruction despite repeated inhalation of a beta 2-adrenergic substance is usually caused by inflammation. Depending on the clinical status and changes of PEF the patient can, if properly instructed, start corticosteroid treatment in case of acute deterioration or increase the corticosteroid doses in case of subacute deterioration of the condition. Follow-up of PEF is important also for self-management in case of clinically latent deterioration and during maintenance treatment. PMID- 1455764 TI - [Climate therapy, rehabilitation and psychotherapy in bronchial asthma]. AB - The authors explain the principle of effectiveness as regards treatment of bronchial asthma (AB) in the climate of the Tatra mountains. The most important place is held by elimination of noxious substances from the patient's environment which is comparable with the eliminations test. The second place is held by factors of a medium stimulating climate which calls for adaptation of the organism. This happens during the three-week acclimatization stage which acts as non-specific therapy. The result of climatotherapy is an increased immunological resistance, hardening, reduced bronchial hyperreactivity and improved life of asthmatic patients. Supplementary treatment comprises respiratory rehabilitation and psychotherapy. The aim of rehabilitation is active participation of the patient in treatment, adequate type of respiration and better tolerance of physical strain. The purpose of psychotherapy is to help the patient to overcome fear of AB, induce a change of lifestyle and regime. After comprehensive institutional treatment the patients are prepared for self-supporting ambulatory treatment. Under institutional conditions antiasthmatic treatment can be discontinued in as many as 24% of asthmatic patients and reduce substantially the administration of inhalatory beta-adrenergic substances, as demonstrated by the authors on 1725 asthmatic patients. PMID- 1455765 TI - [Correct inhalation technique--an integral part of rational treatment of bronchial asthma]. AB - In the rational treatment of asthma bronchiale in recent years a marked increase can be observed as regards prescription of beta-2-agonists and glucocorticoids. They are administered almost exclusively from metered dose inhalers (MDI) with an adjustable valve. Almost half the users do not know the correct inhalation technique. Unless that is used, the effect of drugs is markedly reduced. The author deals therefore in his review in detail with all aspects of a correct inhalation technique; above all he emphasizes slow inhalation with subsequent breath retention which is the only way how to achieve maximum penetration of particles to the final branches of the bronchial tree. The author mentions also spacers which improve in some patients the effectiveness of aerosol treatment. PMID- 1455766 TI - [Fructose metabolism disorders and infusions]. AB - The authors give an account of views regarding the use of non-glucose energy sources in parenteral nutrition during the immediate post-load period/serious operations, severe injuries). Attention is devoted to the metabolic pathway of fructose and its disorders. In hereditary fructose intolerance an infusion of D fructose or D-glucitol (= sorbitol) can induce life threatening hypoglycaemia (unless glucose is administered concurrently). According to some views, in subjects with this intolerance the organism is threatened also by hepatic and renal failure; their development may be independent on hypoglycaemia. Fructose and D-glucitol (sorbitol) therefore should not be administered by the parenteral route. This view is supported by cases where hereditary fructose intolerance could not be revealed from the case-history and clinical manifestations. Some countries have already eliminated fructose and D-glucitol (sorbitol) from their pharmacopoeias. PMID- 1455767 TI - [Synergic joint diagnostics]. AB - The author emphasizes the necessity to use all clinical and paraclinical examination methods in rheumatology to assess an early and correct diagnosis of rheumatic diseases. She emphasizes the importance of examination of the articular punctate and importance of the synoviogram in differential diagnostic considerations. The author reflects also on the importance of the frequently omitted unpretentious examination method--needle biopsy of the joints. PMID- 1455768 TI - [The methodological bases for shaping the academic and scientific discipline of automation in medical service management]. PMID- 1455769 TI - [Vagotomy in the treatment of duodenal ulcers]. PMID- 1455770 TI - [Diagnostic and treatment problems in malignant neoplasms]. AB - The article gives the comparative estimation between the state of oncological aid in the system of the civilian health care and military medicine. The authors analyse the most frequent defects in diagnosis and treatment of malignant new growths. The article focuses the attention of physicians on an early diagnosis of malignant new-growths, necessity to improve their oncology-oriented skill, and render an adequate oncological aid to the servicemen. PMID- 1455771 TI - [The choice of the surgical treatment method in splenic injuries]. PMID- 1455772 TI - [The transpubic surgical approach and experience with using it to treat posttraumatic strictures of the posterior urethra]. AB - Anatomic researches on 15 cadavers of male adults were conducted to study the transpubic access to the urethra and substantiate its possible application for the treatment of the urethral strictures. The authors make a comparative evaluation of transpubic and perineal methods of the access. As for basic indices (the depth of operative wound, direction and the angle of the operative axis inclination), the transpubic method of access has a number of advantages over the perineal access, and is an optimal one for surgical interference on the urethra. The transpubic access was applied on 21 patients who were operated for strictures or obliterations of the urethra. In all the patients the transitivity of the urethra was restored. No complications were marked. PMID- 1455773 TI - [Anesthesia of the cervical plexus in surgical interventions on the neck and its organs]. AB - The author proposes a new method for anesthesia of neck plexus, which is seen to be more safe, has reliable points of reference, and is administered by "one touch" injection. The article gives a description of this method, results of its clinical application, indications and counter-indications. The anesthesia of neck plexus was applied on 71 patients. No complications were marked. This method makes it possible to produce an adequate anesthesia in vast operations on neck and its organs. PMID- 1455774 TI - [The experience of using Ditec in bronchial asthma]. PMID- 1455775 TI - [The clinico-diagnostic aspects of the restorative-reconstructive treatment of patients with defects and deformities of the perioral area]. PMID- 1455776 TI - [The clinico-angiographic aspects of ischemic heart disease]. PMID- 1455777 TI - [The current problems in the development of Russian medical science. Interview by A. P. Lomakin]. PMID- 1455778 TI - [Delta infection in patients with chronic liver diseases]. PMID- 1455779 TI - [Experience with the use of magnetic resonance tomography]. PMID- 1455780 TI - [Cerebrovascular disorders in the innominate artery syndrome]. PMID- 1455781 TI - [The diagnostic significance of the sociomedical indices of the nonregulation interrelationships of servicemen on active service]. PMID- 1455782 TI - [The life expectancy of regular military personnel]. PMID- 1455783 TI - [The performance quality of a flight trainer operator under conditions of heat discomfort]. AB - The studies were conducted on 5 sound operators, age 26-44. The flight simulator was placed into a heat chamber with temperature range from 25 degrees C to 60 degrees C. In these conditions the operators had to withstand pitching and rolling in "horizontal flight" within 6 min. The piloting performance on simulator was conducted by the operators every 10 min. per one hour. 48 tests were carried out. The studies have shown the phase character in roll error at the temperatures of 60 degrees C. The authors make a conclusion that the moderate hypothermia could optimize the operator's performance, and the deep one could worsen it. PMID- 1455784 TI - [The prevention of acute oxygen starvation during underwater swimming]. PMID- 1455785 TI - [A method for analyzing the work of a medical supplies installation]. PMID- 1455786 TI - [The stability and quality control of ditilin preparations (a review of the literature)]. AB - In aqueous solutions dithylinum decomposes with formation iodine, choline, succinic acid and its monoether. The rate of decomposition depends on the conditions of storage, and also upon the concentration and ion force of solution, existence of ion metals and some other factors. The article proposes methods for identification and quantitative analysis of dithylinum and the products of its hydrolysis. The requirements imposed for storage or transportation of dithylinum solutions: not frost and temperature level not higher than 5 degrees C. PMID- 1455787 TI - [An isolation compartment for performing air-radon baths]. PMID- 1455788 TI - [Measures to improve the medical service of the U. S. Army]. PMID- 1455789 TI - [The management of military medical research in the USA]. PMID- 1455790 TI - [The basic directions in improving the work of military polyclinics]. PMID- 1455791 TI - [A low-frequency alternating magnetic field and its combination with radon baths in juvenile rheumatoid arthritis]. AB - Children suffering from juvenile rheumatoid arthritis (JRA) (n-132) were exposed to low-frequency variable magnetic field. Therapeutic response registered consisted of analgetic and anti-inflammatory effects most pronounced in 14-19 mT regimen. The addition of radon baths to the above exposure resulted in higher effectiveness of the treatment due to involvement of pathogenetic JRA mechanisms. PMID- 1455792 TI - [A new method for treating rheumatoid arthritis patients by electrophoresis using mefenamic acid]. AB - The paper provides clinical and experimental reasoning for application of a new treatment for rheumatoid arthritis (RA) implying electrophoresis of an anti inflammatory drug mefenamic acid from dimexide solution. Complete and partial responses registered in 125 patients, reached 75%. With the new method it is possible to relieve pain, correct immunity and stop inflammation. The best effect was shown in an inactive disease and in activity phases I and II in adjuvant use of the method. PMID- 1455793 TI - [The correction of functional disorders of the bile-secreting system by using laser radiation]. AB - He-Ne laser irradiation of biologically active points and infrared laser irradiation of the liver were employed to improve gallbladder and sphincter functions, bile production and biochemistry, respectively, in a total of 57 patients with biliary dyskinesia presenting as hypokinetic dyskinesia of the gallbladder, hyperkinetic dyskinesia of the sphincter of Oddi or the combination of the two affections. Simultaneous use of the two kinds of laser irradiation appreciably shortens treatment duration, abolishes biliferous dysfunction, reestablishes physiological balance of bile components in case of its initial lithogenic potential. PMID- 1455794 TI - [The effect of the bitemporal use of an ultrahigh-frequency electrical field on the central hemodynamic indices and the phase structure of the heart cycle]. PMID- 1455795 TI - [The phonophoresis of solutions of a "dry" mud extract in the therapy of patients with chronic gastritis]. AB - The study of stomach morphology and function in chronic gastritis treated with phonophoresis of dry mud extract solutions demonstrates a stimulating effect of the treatment on acid production. A positive response was also registered on the part of the structure of gastric mucous lining and functional activity of this epithelium. PMID- 1455796 TI - [Electromagnetic waves in the combined therapy of children with birth injuries to the brachial plexus]. PMID- 1455797 TI - [3H-thymidine incorporation into the nuclear DNA of cells of the cerebral cortex under microwave action]. PMID- 1455798 TI - [The modelling of the cavitation processes during the focusing of the shock wave in an electrodynamic lithotriptor]. AB - The paper reports an experimental technique and the results obtained in the study of cavitation arising in focusing the shock wave of electrodynamic lithotriptor. The aim of the above study was to specify mechanisms of soft tissue lesions during destruction of nephroliths with lithotriptor impulses. Cavitation regions were found along the axis of the generator focusing system and at its outgoing sites as a result of the boundary expansion wave. This phenomenon by the body margin is attributed to transformation of a positive pressure impulse into the tension impulse. As the shock wave pressure impulse is much more significant than the pressure impulse of the boundary expansion wave it is most probable that cavitation-induced lesions appear at the site of the wave exit from the body. PMID- 1455799 TI - [The action of a pulsed magnetic field on the electrical resistance of the skin]. AB - The skin of 32 rabbits and 10 patients (7 males and 3 females aged 32-48) was exposed to impulse magnetic field (IMF) with intensity of 1.0-1.5 T and frequency of 45 paired impulses a minute. The 5-minute exposure resulted in a 50% decrease in the skin electrical resistance both in patients and animals. On aftertreatment minute 2 the resistance started recovering and returned to the baseline on minute 6 in animals and 4 in patients. Changes in electrical resistance of the skin are attributed to emergence of IMF-related electrical induction. PMID- 1455800 TI - [The regeneration of therapeutic muds from Varzi-Iatchi health resort]. PMID- 1455801 TI - [A new deposit of naftusia in Truskavets]. PMID- 1455802 TI - [The microcirculatory dynamics of patients with ischemic heart disease undergoing balneotherapy with Shmakovka narzan]. PMID- 1455803 TI - [Dopplerographic follow-up of the cerebral hemodynamics during the pelotherapy of spinal osteochondrosis in patients suffering from ischemic heart disease]. PMID- 1455804 TI - [The evaluation of the results of the bicycle ergometry training of students with an inactive phase of rheumatism]. AB - 157 students with compensated mitral insufficiency in inactive rheumatism exercised on bicycle ergometer. Matched controls did not exercise. The analysis of cardiorespiratory parameters showed advantages of the training. Being statistically significant, these advantages support introduction of the method into wide practice. PMID- 1455805 TI - [The effect of radon baths on the rheological properties of the erythrocytes in osteochondrosis patients]. PMID- 1455806 TI - [The use of the means of therapeutic physical exercise for the combined correction of the hemodynamics in miners with venous insufficiency of the legs]. PMID- 1455807 TI - [Medical gymnastics in the subclinical birth injury syndrome syndrome of shoulder girdle amyotrophy in adolescents]. PMID- 1455808 TI - [Mechanotherapy in the combined sanatorium-health resort treatment of patients with radicular ischemia]. PMID- 1455809 TI - [The efficacy of the treatment at Bayram-Ali sanatorium of patients with glomerulonephritis]. PMID- 1455810 TI - [A new treatment method for constipation]. PMID- 1455811 TI - [The combined action of an ultrahigh-frequency electrical field bitemporally and decimeter waves on the thymus area in the combined therapy of rheumatoid arthritis patients]. AB - The thymus of rheumatoid arthritis (RA) patients was exposed to combined action of bitemporal UHF electric field and decimeter waves to study immunomodulating effect of the combination. Biochemical, immunological and endocrinological findings during the patients follow-up gave evidence for conclusion on activation of the hypothalamic-hypophyseal-thymic axis. A response was achieved in RA seronegative variant with concomitant synovitis. This may be due to genetic factors. PMID- 1455812 TI - [The effect of korinfar and anaprilin on lipid peroxidation and the antioxidant system in hypertension patients]. AB - Changes of lipid peroxidation products and activity of the antioxidant system during corinfar and anaprilin treatment were studied in 36 patients with hypertensive disease (stage II). A decrease of the content of malondialdehyde and dien conjugates was revealed in the blood of these patients after a course of treatment with these agents. Simultaneously, the antioxidant protection of the blood increased: the concentration of reduced glutathione increased, the activity of glutathione peroxidase rose. The changes of oxidated glutathione were not clear. It is suggested that such character of the effect of corinfar and anaprilin on the processes of lipid peroxidation is the result of a direct effect on lipid peroxidation products and also compensatory activation of enzymatic reactions of restoration of natural cellular antioxidants as well as enzymatic system directly utilizing lipoperoxides. PMID- 1455814 TI - [The importance of crystallography for the diagnosis of biliary dyskinesia]. PMID- 1455813 TI - [The evaluation of gallbladder contractile function and the ultrasonic signs of chronic noncalculous cholecystitis]. AB - A correlation of the clinical picture of the disease, results of ultrasonic examination (USE) of the gallbladder and laboratory findings in 120 patients with chronic noncalculous cholecystitis has been evaluated. The contractile function of the gallbladder by USE was carried out 25 minutes after intake of 30 ml of olive oil. A correlation has been established between the severity of the clinical picture and echoscopic signs in chronic cholecystitis. The most frequent symptoms of chronic cholecystitis as evaluated by USE were association of thickening and hardening of one of the gallbladder walls and non-homogeneity of the gallbladder. The olive oil test is important in the ultrasonic examination. PMID- 1455815 TI - [The results of treating pulmonary tuberculosis patients with different concomitant diseases by using millimeter-wave resonance therapy]. AB - The authors investigated the clinical and biochemical efficacy of millimeter-wave resonance therapy in patients with destructive pulmonary tuberculosis associated with different concomitant diseases. It was established that inclusion of millimeter-wave resonance therapy in the complex treatment of this patient category favoured the efficacy of tuberculosis treatment. The treatment produced also a favourable effect on concomitant diseases. PMID- 1455816 TI - [The use of a sodium lactate solution in the combined conservative treatment of patients with kidney stones]. AB - A method is presented of complex medical treatment of patients with nephrolithiasis including intravenous systemic alkalinization of the urine with 1/6 M solution of sodium lactate, litholysis by citrates, use of urostatics and mineral waters of local origin. It is shown that complex medical treatment of nephrolithiasis including systemic alkalinization of the urine with a 1/6 M sodium lactate solution may be considered as a method of choice in obstructing calculi as non-operative treatment. PMID- 1455817 TI - [Immunological disorders in pregnant women with inflammatory kidney diseases and nephropathy]. AB - The humoral and cellular immunity was investigated in 168 pregnant with different diseases of the kidneys. A detailed study of the blood lymphocyte population, immunoglobulins, immune complexes, hemolytic activity revealed changes of immunologic homeostasis which may be used as diagnostic criteria of activity of the pathological process and for treatment tactics. PMID- 1455819 TI - [The clinical picture, diagnosis and treatment of chronic subdural hematomas]. AB - A study is presented of 37 cases of chronic subdural hematomas. Initial manifestations: headache, epileptic seizures, mental disorders. Involvement of the III, V, VII cranial nerves, anisocoria almost in 50% on the contralateral side were noted. CSF xanthochromia is of certain diagnostic significance. Carotid angiography is the most informative method. Osteoplastic trephination with evacuation of the hematoma is the method of choice. PMID- 1455818 TI - [The korinfar and actovegin treatment of patients with a chronic ischemic disorder of the cerebral circulation]. AB - A study is presented of 42 patients with different stages of dyscirculatory encephalopathy of atherosclerotic genesis who showed disorders of the cerebral hemodynamics, microcirculation, increase of the aggregational capacity of thrombocytes and activation of lipid peroxidation. The patients were treated with corinfar and actovegin and this resulted in normalization of the microcirculation and rheological properties of the blood. Corinfar also reduced activation of lipid peroxidation processes. PMID- 1455820 TI - [The antioxidant treatment of patients with acute intestinal infections due to gram-negative microorganisms]. AB - It was established that administration of S. typhimurium lysate causes activation of the processes of free-radical oxidation. Introduction of unithiol in combination with magnesium sulfate returns the intensity of these processes to the initial level. Unithiol and alpha-tocopherol acetate protect the animals form lethal effects of S. sonnei lysate. Use of a combination of pharmacological agents consisting of unithiol, magnesium sulfate and alpha-tocopherol acetate in the treatment of patients with acute intestinal infections due to gram-negative pathogens (shigellae, salmonellae, proteus, klebsiellae, pseudomonas) resulted in decrease of the length of the intoxication and diarrhea syndrome, decrease of the frequency of repeat bacteria elimination and protracted forms of these infections, more rapid normalization of immune system functions. PMID- 1455821 TI - [The immunocorrective therapy of patients with acute dysentery]. PMID- 1455822 TI - [The modern concept of the diagnosis and treatment of bronchial asthma (a lecture)]. PMID- 1455823 TI - [The biological role and clinical significance of protein C]. PMID- 1455824 TI - [Genetic research in tubercular pulmonology (a review of the literature)]. PMID- 1455825 TI - [The autopsy: its importance for modern clinical medicine]. AB - Autopsies are absolutely necessary for the progress of modern clinical medicine and for solving many problems: diagnostic, control of treatment quality, detection of infectious, hereditary and systemic diseases, establishing causes and mechanisms of sudden death, qualification of unclear diseases and syndromes, classification and nomenclature of nosological entities, detection and study of spontaneous and induced pathomorphosis. The pathologist performing autopsies should except necropsy also make macrochemical examination and send the material for microbiological and biochemical examination. Special attention should be paid to establishing the diagnosis and clinicoanatomical epicrisis. Undoubtful is the role of autopsy in teaching and training, postgraduate education, accumulation of archives and their retrospective analysis, creation of macro- and micromuseums of human diseases. Physician's errors, general requirements and cadaveric tissue observation are also discussed. PMID- 1455826 TI - [Gangrene of the foot as a manifestation of distal polyneuropathy in diabetic patients (a review of the literature)]. PMID- 1455827 TI - [Ionizing radiation and neoplasms of the thyroid (a review of the literature)]. PMID- 1455828 TI - [Borderline neuropsychic disorders in persons subjected to ionizing radiation exposure]. AB - Results were compared of a study of mental disorders in 365 participants of liquidation of sequelae of the Chernobyl atomic station disaster subjected to the effect of ionizing radiation showing psychic disorders, in 475 somatic patients and in 42 Afghan soldiers suffering of traumatic cebrebrasthenia. Clinical aspects of manifestation of nervous and mental disorders and their effect on the dynamic structure of mental and somatic premorbid state, presence of somatic diseases, specific psychotrauma situation and organic effects of the ionizing radiation. Stages of development of these disorders were singled out and signs of their endogeneity and progression were established. The possibilities of psycho social adaptation are discussed. PMID- 1455829 TI - [The hormonal functions regulating carbohydrate metabolism in participants in the cleanup of the sequelae of the accident at the Chernobyl Atomic Electric Power Station with a neurocirculatory dystonia syndrome]. AB - Radioimmunoassay revealed in participants of Chernobyl disaster sequelae preclinical changes of some hormonal functions: moderate increase of the basal concentration of blood insulin, somatotropin, C-peptide against the background of persistent hypercortisolemia. Increase of the level of "hyperglycemic" hormones (cortisol, somatotropin, C-peptide) is explained by adaptative and compensatory reactions of the body in response to lesioning effects of ionizing radiation and other negative factors of the Chernobyl accident. Relative hyperinsulinemia is, apparently, compensating the total hyperglycemic effect of these hormones leading to stabilization of the blood sugar level. PMID- 1455830 TI - [A case of a radiation lesion in the city of Kirovograd]. PMID- 1455831 TI - [The effect of laser irradiation of the blood on the adenosine triphosphatase activity of the erythrocyte membranes and on the cardiac activity indices in patients with ischemic heart disease]. AB - The activity of potassium, sodium, magnesium and Ca-ATP-ase of the erythrocytic membrane, index of erythrocyte deformability, changes of the hemodynamics and some cardiac function during bicycle ergometry [correction of veloergometry] tests before and after a course of laser irradiation of the blood were studied in 36 patients with exertion stenocardia. It was established that laser therapy is accompanied by increase of the activity of ATP-ase, index of erythrocyte deformability and positive changes of the cardial function. The possibility is discussed of improving the cardiac function under the effect of laser irradiation as a result of optimization of the structural-functional organization of the cellular membrane. PMID- 1455832 TI - [Radionuclide ventriculography as a method for assessing the functional status of the heart ventricles in patients with supraventricular tachycardia]. AB - Left and right ventricular function was evaluated by means of radionuclide ventriculography in 44 patients with paroxysms of supraventricular tachycardia without sings of circulatory insufficiency of coronaro- and noncoronarogenic origin. Depending on the efficacy of antiarrhythmic treatment the patients were subdivided in two groups: patients amenable to treatment and patients with refractory arrhythmia. It was established that radionuclide ventriculography allows to objectively evaluate the functional state of both ventricles and to reveal early signs of deterioration of the hemodynamic productivity of the heart in patients with paroxysms of supraventricular tachycardia. Reduction of the pumping function of the right ventricle in patients with refractory tachycardia along with hyperkinesia of its separate segments, changes of left ventricular rate and an increase of the terminal diastolic and systolic volumes of both ventricles without changes of the stroke volume may be a criterion of refractoriness of arrhythmia in this category of patients. PMID- 1455833 TI - [The circadian rhythm dynamics of myocardial ischemia in patients with unstable stenocardia during one year of observation]. AB - Dynamics of circadian rhythms of myocardial ischemia in patients with nonstable stenocardia within one year of observation was studied in 50 patients by means of Holter monitoring. By the second admission depending on the clinical course of the disease 4 groups of patients were singled out and their painful and nonpainful heart ischemia was assessed with 6-hour intervals. Comparison of results of painful arrhythmia during the first and repeat admission indicated that the diurnal dynamic and peaks of myocardial ischemia duration coincide as to time and direction. Nonpainful ischemia appears mainly during the night hours. PMID- 1455834 TI - [Changes in the parameters of the central and regional hemodynamics in patients with unstable stenocardia treated by the methods of quantum hemotherapy]. AB - A study of 116 patients with nonstable stenocardia (age of the patients: 29-68 years). In 54 of them laser irradiation of the blood (LIB) was used, in 62- autorheography revealed a selective character of influence of LIB and ATIB on the hemo-hemotransfusion of irradiated blood (ACIB) and 32 received only drugs. Tetrapolar dynamics: tendency to averaging of the cardiac ejection. In patients with initially low values--an increase and with initially high values--a reduction. Possibly, this reaction has a nonspecific character and reflects the reaction of circulation to stabilization of the patients' condition. The hemodynamic parameters did not deteriorate below critical levels. Hence, these methods may be used in patients with nonstable stenocardia associated with initial disorders of the central and peripheral hemodynamics. PMID- 1455835 TI - [The significance of the association of erythrocytic antigens in rheumatism]. AB - A study is presented of ABO system, rhesus, MN, P, Lewis factor in 78 patients with rheumatism. Taken separately their information value was low. At the same time in patients with O (I), A (II), B (III) blood groups association of antigens were often met that allows to isolate among healthy persons groups of high risk as related to rheumatism with the purpose of realizing primary prophylaxis. PMID- 1455836 TI - [The effect of microwave resonance therapy and hypnotherapy on the links in the pathogenesis of peptic ulcer]. AB - Results of a study are reported of a study of the concentration of biologically active substances such as histamine, serotonin, noradrenaline, adrenalin, corticotropin and indices of gastric secretion in ulcer disease patients at the stage of exacerbation receiving microwave resonance therapy and hypnotherapy. The obtained results evidence that hypnotherapy and microwave resonance therapy are pathogenetic methods of treatment of patients with ulcer disease. Combined treatment proved more effective. PMID- 1455837 TI - [Fibronectin and the phagocytic activity of the neutrophilic granulocytes in patients with different clinical variants of bronchial asthma]. AB - A study of 125 cases of bronchial asthma revealed low contents of fibronectin. The degree of the decrease depended on the severity of the clinical course of the disease and treatment with glucocorticoid hormones. Patients with bronchial asthma showed an essential reduction of the number of neutrophilic granulocytes capable of phagocytosis. In the process of incubation of polynuclears with fibronectin occurs restoration of their phagocytic activity which was less pronounced in patients receiving glucocorticoids. PMID- 1455838 TI - [The role of pharmacological tests in detecting disorders in the bronchial patency and bronchial reactivity of patients with chronic glomerulonephritis]. AB - Data are reported of a study of the effect of atrovent, salbutamol and acetylcholine on bronchial patency and reactivity of the bronchi in 89 patients with glomerulonephritis (age: 17-49 years) with normal renal function and at the stage of chronic renal failure. The tests proved highly informative. Latent bronchospasm was found in 12.1% of patients with chronic glomerulonephritis. In 76.3% of patients at the stage of chronic renal failure hyperreactivity of the bronchi was found. The revealed changes require early diagnosis and treatment. PMID- 1455839 TI - [The intestinal mechanisms of the protein metabolic disorder in kidney failure]. AB - Data are reported on intestinal mechanisms of protein metabolism in renal failure in patients and experimental animals. These disorders are characterized by inhibition of the intestinal absorption capacities, disturbances of intestinal mechanisms of the amino acid kinetics and they develop along with a reduction of the total excretory renal function. PMID- 1455840 TI - [Acute gastrointestinal hemorrhages]. AB - It was thought formerly that gastrointestinal hemorrhage is an integral part of gastric ulcer. At present this is not a regularity, occurs only in some patients with ulcer disease and in other kinds of pathology (liver cirrhosis, dilated esophageal veins and oth.). Surgical treatment during hemorrhage is connected with risk for the patients. We recommend temporary tamponade of the bleeding blood vessels, improvement of the general condition of the patient and then transferring the patient to a surgical department for determination of further tactics. PMID- 1455841 TI - [Lipidemia in the nephrotic syndrome and the atherogenicity of the plasma]. AB - The nephrotic syndrome is characterized by proteinuria, hypoalbuminemia and hypercholesterolemia. Hypercholesterolemia is in some cases a risk factor for atherosclerosis in this group of patients. The lipid plasma spectrum was studied in 45 patients with the nephrotic syndrome. Most pronounced changes of the lipid composition of the plasma were revealed in patients with systemic lupus erythematosus and a special form of mesangio-proliferative glomerulonephritis which is characterized by a torpid course and rapid development of chronic renal failure. Plasma atherogenicity was calculated according to the index of plasma atherogenicity. A high atherogenicity index was revealed in patients with an association of the nephrotic syndrome and arterial hypertension. Plasma atherogenicity is determined mainly by the level of high-density-lipoprotein cholesterol. PMID- 1455842 TI - [The characteristics of lipid peroxidation in patients with an acute disorder of the cerebral circulation]. AB - A study is presented of 89 inpatients with cerebral stroke. Lipid peroxidation was determined during the first days of the diseases (1-7 days). The state of the patients was evaluated by the clinical picture, manifestation of neurological symptoms, biochemical indices of the blood, coagulogram, ECG, REG, state of lipid peroxidation. The obtained data suggest a major role played by lipid peroxidation of the cell membranes, its elevation in of the activity in stroke. The concentration of lipid peroxidation depends on the severity of the condition and, thus, it may be used for evaluation of treatment efficacy and prognosis of the disease. PMID- 1455843 TI - [The effect of death cup poison on the morphology of human erythrocytes]. AB - Incubation of heparinized blood of donor (37 degrees C) resulted in an insignificant amount of changed erythrocyte, forms mainly at the expense of stomatocytes and echinocytes, reduction of medium diameter and sphericity index. In incubation of blood with Amanita phalloides [correction of Agaricus bulbosus] poison (0.5LD100) changed forms made up 66.2% with prevalence of poikylocytes, schizocytes and hemolyzed forms. PMID- 1455844 TI - [The setting of hygienic standards for the insecticide sonet in potatoes]. AB - A study of the toxic properties of sonet in chronic experiment on white rats established the threshold and non-acting dose of the insecticide. The accumulation of the insecticide in the potato tubers during the entire vegetation period as well as its effect on the potato quality were investigated. The author recommends 0.05 mg/g of sonet per 1 g of potato as a maximum permissible level. PMID- 1455845 TI - Is asthma an inflammatory disease? AB - In the 1950s, asthma was defined in terms of reversible airflow obstruction; and then during the 1980s, the emphasis on the diagnosis and treatment of asthma centered on airway hyperreactivity. Recent advances in molecular biology and immunopathology have focused diagnosis and treatment of asthma on inflammatory mechanisms. This article briefly reviews some of the inflammatory components of asthma and the rationale for using inhaled (topical) anti-inflammatory agents in treatment. It also calls attention to some potential and actual adverse effects of inhaled corticosteroids. It mentions some agents used as alternate therapy for "steroid resistant" patients. The alteration of airway immunopathology of asthmatics before and after use of inhaled corticosteroids is described. There is evidence that treatment directed solely towards airway inflammation without use of inhaled B-agonist agents does not eliminate airway hyperresponsiveness. PMID- 1455846 TI - Nursing research with refugees. A review and guide. PMID- 1455847 TI - Challenges of nursing research with the frail elderly. PMID- 1455848 TI - The homeless population. PMID- 1455849 TI - Nursing in Nazi Germany. AB - German nursing did indeed change during the Nazi period. There were external changes, in terms of the improved social status of nursing, the tightening and unification of professional nursing organizations, the laws affecting nursing, and the politicization of the profession. Articles written by nurses at the time and more recent interviews suggest that there were internal changes as well. It appears that at least a portion of German nurses accepted the National Socialism reinterpretation of professional nursing ethics and humanitarian principles in the assumption that through their obedience they were doing good. This historical research points to clear lessons for contemporary nurses. Nurses in Nazi Germany were under the illusion that they were remaining true to their professional ethics, unaffected by the social change around them. This apolitical professional consciousness made it possible for the profession to be subsumed as a part of the larger political system. I believe that we must be clear that nursing never takes place in a value-free, neutral context; it is always a socially significant force. This means that we cannot simply observe what is taking place around us but must take a stand and get involved, helping to shape sociopolitical developments. I also believe that we must deal with the history of our profession, especially its darkest hours, so that we may remain sensitive to any signs of inhumanity. We must call into question traditional principles, such as obedience, and replace them with professional competence, professionalism, and creative self-consciousness. And not least, we have a moral obligation to the millions of victims of National Socialism, even if it only means that, through historical research, we assure that they are not forgotten. By taking responsibility for this part of our history, we can become more sensitive for the future, with eyes and ears open for all social injustices. PMID- 1455851 TI - Health behaviors and health risks among homeless males in Utah. PMID- 1455850 TI - Examining vulnerability of women clerical workers from five ethnic/racial groups. PMID- 1455852 TI - The dying art of bandaging. PMID- 1455853 TI - [Evaluation of clinical effectiveness and adverse effects of Polnitrin]. AB - In a double-blind, randomized, placebo cross-controlled trial the effectiveness and the adverse effects of two types of buccal tablets containing 5 mg nitroglycerin: Polnitrin produced by Warsaw Pharmaceutical Works POLFA and its analogue of foreign origin, were assessed. The third compared preparation was sublingual nitroglycerin in 0.5 mg tablets. The longest dissolution in the buccal cavity showed Polnitrin (mean 6.6 hours). Polnitrin significantly increased the resting heart rate during 3 hours, and during 6 hours at maximal effort. The foreign analogue decreased significantly the systolic pressure during 3 hours after application. No significant differences were noted in the effects on the basic haemodynamic parameters between the compared buccal tablets. Exercise tolerance and coronary reserve were assessed with repeated exercise tests on moving track (Marquette Case-12). Immediately after being stuck to the gum Polnitrin, its analogue and sublingual nitroglycerin significantly prolonged the marching time: total, till pain, and till ischaemia. After 6 hours the marching time till pain appearance was significantly longer after Polnitrin than after placebo or its analogue. Local adverse effects connected with the presence of the tablet in the oral vestibule may hamper the treatment with Polnitrin in some cases. The most frequent side effect were headaches which are known to occur usually after all nitrates. PMID- 1455854 TI - [Effect of resuming occupational work after myocardial infarction on recurrence and mortality]. AB - The effect of resuming occupational work on the mortality and the frequency of infarction recurrence was studied in a group of 771 patients with a history of at least one myocardial infarction. The group of 216 patients who resumed occupational work in industry or administration were compared with 280 patients remaining without occupation, and another comparison was done between 170 patients working and living in towns and 131 working on farms. The material was divided also according to prognostic groups: good, moderately good and poor. All patients were aged over 60 years. The follow-up was 2 to 10 years. A beneficial effect was found of continuation of occupational work, with the exception of heavy physical work, after infarction in the first 3 years. PMID- 1455855 TI - [Structure of psychological needs of patients over 60 years of age, hospitalized for ischemic heart disease complicated by asthenic- depressive syndrome, and in healthy persons]. AB - Using psychotherapy methods such as MMPI-Wiskad, ACL-37 and 16PF the patterns of psychological needs were studied in postproductive-age subjects with ischaemic heart disease complicated or not with asthenia-depression syndrome and in healthy subjects. Statistical analysis showed that in relation to old people with ischaemic heart disease or without it patients with ischaemic heart disease and depression with asthenia showed a higher psychological sensitivity and their needs were concentrated around the need for self-manifestation, aid-seeking and taking care of oneself. In old people a tendency was maintained for persistence of psychological needs in the previously formulated forms. PMID- 1455856 TI - [Effect of smoking on the indicators of immunity and the acute-phase reaction in persons professionally exposed to solvents]. AB - In 156 men, 46 non-smokers, 47 smokers, 19 non-smokers exposed to organic solvents and 41 smokers exposed also to solvents the levels of immunoglobulins, lysozyme, C3c, C4, alpha 1-acid glycoprotein, coeruloplasmin and haptoglobins were determined in serum, besides that the counts of circulating T, B and non-T non-B lymphocytes were calculated. A synergistic depressing effect of cigarette smoke and organic solvents was found on certain immunity parameters. This depression was manifested also as changes in the concentrations of IgA, IgD, IgG, lysozyme and T-lymphocyte subpopulations. PMID- 1455857 TI - [Socioeconomic factors and the incidence of premature labor in a polluted environment]. AB - The effects of socioeconomic factors on the incidence of premature births were studied in Chorzow. For a better evaluation of the socioeconomic conditions a scoring system was used based on such parameters as marital status of the mothers, educational level, living conditions, flat equipment, property owned by the family and economic status. The incidence of prematurity was 14.1%. In over 40% of cases premature births were associated with poor conditions of life. Occupational work under stressful conditions significantly increased the rate of prematurity. After a review of similar studies of other authors it is accepted that environmental pollution is an additional risk factor for the fetus. PMID- 1455858 TI - [Pseudotumor cerebri in children]. AB - The authors observed 6 cases of brain pseudotumours in children aged from 3 to 15 years. All patients had been referred with the diagnosis of brain tumour, with headaches, eye fundus changes fundus changes. Some children had nystagmus, squint, vomiting and dizziness. One child had pharyngitis, two had sinusitis. Contrast brain examinations gave normal results. Diet with salt and fluid restriction and oedema-reducing drugs (glycerol, mannitol, decadron) were used. In all patients the neurological and ophthalmological signs regressed within 3 to 12 weeks. PMID- 1455859 TI - [Basic indicators of physical development of schoolchildren living in the area of an industrial plant processing non-ferrous metals]. AB - The purpose of the study was an analysis of the basic indices of somatic development of school children in the Olkusz area with mines of zinc, lead and cadmium, and metallurgic plants processing the ores of these metals. The studied group comprised 747 children aged 5 to 14 years attending randomly selected schools in Olkusz, Bukowna and Boleslaw. The height and body mass were measured on medical scales with height scale. The obtained results were compared with those of similar measurements of children in other parts of the country with different degrees of environmental pollution with non-iron metals. In the Olkusz area the height of the children was slightly smaller than in other parts. PMID- 1455860 TI - [Effectiveness of Cefobid in pediatric practice]. AB - The sensitivity to Cefobid was evaluated in vitro in 37 bacterial strains obtained from 37 patients. Good effectiveness of the drug against the strains was found in 78.3%, moderate in 13.5%, none in 8.2%. The clinical examinations were carried out in 16 children and again a high clinical effectiveness of Cefobid was found, with cure in 14 cases (87.5%). Cefobid was ineffective in 2 children with infection of Tenckhoff catheter, which required finally exchange of the catheter. No side effects of Cefobid were noted. Cefobid is a safe and effective antibiotic which may be given to small children and patients with renal failure. The broad spectrum and the possibility of drug use without dosage modification facilitate the treatment of patients with various grades of renal failure. PMID- 1455861 TI - [Prevention of primary arterial hypertension--effects of various dietary components]. PMID- 1455862 TI - [Creation of intestinal fistulas and the reconstructive procedures in patients after proctocolectomy]. PMID- 1455863 TI - [On the treatment of orbital fractures]. AB - The author discusses the management of fractures of the orbit reviewing the present state of the pertinent knowledge. The diagnostic problems and therapeutic possibilities are mentioned. PMID- 1455864 TI - [Evolution of post-traumatic hematoma of the liver monitored by ultrasonography]. AB - The results of 20 months of follow-up of posttraumatic hepatic haematoma are presented. The haematoma developed as a result of blunt abdominal trauma and was diagnosed intraoperatively. Monitoring was based on ultrasonography. A significant change in the echographic pattern and size of the haematoma indicated its organization. The purpose of the study was calling attention to the ultrasonographic findings in hepatic haematoma in relation to the time after trauma. It is worth stressing that hepatic haematoma healed well although it had not been managed during the operation (even not drained). PMID- 1455865 TI - [Neurofibromatosis of the head and neck]. AB - The source of development of neurofibromas, their incidence, tendency for recurrences and malignant transformation are reviewed. The main signs of von Recklinghausen disease and the difficulties in its diagnosis are discussed. A case of faciocervical neurofibromatosis with recurrences is presented stressing the importance of adequate therapeutic-prophylactic management is stressed, in view of increased predisposition to recurrences and malignant transformation. PMID- 1455866 TI - [Cure of acute myeloblastic leukemia in a child with Down syndrome and tetralogy of Fallot]. PMID- 1455867 TI - [Use of streptokinase in the treatment of thrombosis around the atrial drain of the Pudenz valve in a child with post-inflammatory hydrocephalus]. PMID- 1455868 TI - [A case of early diagnosis of chloride diarrhea]. PMID- 1455869 TI - [Current views on the pathogenesis and treatment of pulmonary emphysema and chronic bronchitis]. AB - In recent years a rising interest has developed among the authors studying the problems of pathogenesis and treatment of chronic bronchitis and pulmonary emphysema in the factors responsible for the immune equilibrium of the respiratory system. In particular, the correlation has been stressed between the levels of inflammation mediators and the activity of proteolytic enzymes and their inhibitors in lung tissue. Most studies seem to confirm the validity of the elastase-antielastase concept. Among the environmental factors directly responsible for the development of these diseases tobacco smoke and other irritant fumes (SO2NO2) are mentioned. This concept had been the foundation for trials of therapeutic use of inhibitors of elastolytic enzymes. PMID- 1455870 TI - Endoscopic management of nonvariceal gastrointestinal bleeding. AB - Endoscopic management of upper gastrointestinal bleeding has been expanded from a purely diagnostic role to a therapeutic role in many patients. In addition to controlling active bleeding, it is an option in a patient who is clinically at a high risk of rebleeding, or in patients who have peptic ulcers with visible vessels or stigmata indicating high risk. Several methods have been studied, and currently the most useful include thermal cautery with the heater probe or bipolar electrocoagulation, and injection using epinephrine and/or sclerosants. Endoscopic hemostasis can effect permanent control of bleeding in many patients, but should be considered complementary to conventional surgical control in other patients, where temporary control to stabilize the patient is a desired end. PMID- 1455871 TI - Approaches to the endoscopic treatment of esophageal varices. AB - Endoscopic therapy is commonly employed for both initial and subsequent definitive treatment of variceal bleeding. Sclerotherapy performed with a flexible endoscope is currently the most widespread technique. Available data suggests that such treatment does not improve outcome in the acute treatment of variceal bleeding (first 30 days) but appears superior to conventional medical management in the long term. Sclerotherapy does not appear better or worse than pharmacological therapy or surgical therapy when these treatments are compared in the elective setting. Although effective, endoscopic sclerotherapy is recognized to be associated with many major and minor treatment-related complications and a significant incidence of recurrent hemorrhage. In response to these shortcomings newer forms of endoscopic therapy such as polymer injection and endoscopic ligation have been developed. Polymer injection appears well suited for patients with active bleeding and for those with gastric varices but does not have advantages for chronic treatment aimed at variceal eradication. Endoscopic ligation appears at least as effective as conventional sclerotherapy for control of acute bleeding and prevention of rebleeding and is associated with few treatment induced complications. While endoscopic therapy will likely continue as the most commonly employed treatment for patients with hemorrhage from esophageal varices, newer methods with wider margins of safety and efficacy seem destined to supplement or replace conventional endoscopic sclerotherapy. PMID- 1455872 TI - Endoscopic intervention for enteral access. AB - Contrary to total parenteral nutrition with its relatively recent introduction into modern clinical medicine, enteral nutrition has a long and colorful history. Prior to development of fiberoptic endoscopy, physicians attempting to feed patients who could not or would not eat were limited to the blind placement of intestinal tubes or radiologically assisted placement of these devices. Previous to these modern attempts, the use of nutrient enemas was attempted for which there was evidence of occasional success. With the introduction of fiberoptic flexible endoscopy, guidance of tubes into the upper intestinal tract under direct vision became feasible. The manner in which tubes were positioned, advanced, or manipulated are myriad and attest to the ingenuity of clinicians. A revolution in endoscopic intervention occurred with the introduction of the percutaneous endoscopic gastrostomy in 1980. This provided secure access to the stomach without a laparotomy. This technique was also modified to allow decompression of the stomach with feeding distally into the small intestine and also direct puncture and placement of tubes into the small intestine. The most recent advance in enteral nutrition is taking place at the present time with the introduction of laparoscopic techniques in the creation of gastrostomies and jejunostomies. PMID- 1455874 TI - Endoscopic management of common bile duct stones. AB - Endoscopic sphincterotomy has become the undisputed method of choice for removing common bile duct calculi following previous cholecystectomy. This approach has also been applied to selected patients with intact gallbladders deemed unfit for surgery. More recently, endoscopic clearance of the bile duct has been used in concert with laparoscopic cholecystectomy to avoid laparotomy. Modalities available for stone therapy via the endoscope include baskets and balloons, mechanical lithotripters, electrohydraulic lithotripsy probes, and laser energy. In difficult cases stents may be placed to provide drainage in lieu of stone extraction. PMID- 1455873 TI - Therapeutic colonoscopy. AB - Therapeutic colonoscopy has replaced or lessened to a significant degree the need or extent of traditional open surgical procedures. The common uses of therapeutic colonoscopy are hemostasis, resection and ablation of benign and malignant disease, decompression and recanalization of obstructed or dilated bowel, as well as foreign body extraction. Bleeding from arteriovenous and other vascular abnormalities can be controlled with 40% to 80% success rates using endoscopically delivered, monopolar, bipolar, or laser coagulation. The palliation of bleeding recurrent or inoperable colorectal cancer is achieved in up to 90% of patients. Virtually all pedunculated adenomas and most sessile adenomas are regularly removed colonoscopically, while large and recurrent villous adenomas in high risk individuals can be successfully managed by endoscopically delivered laser ablation techniques. Emergency colonoscopic reduction of sigmoid volvulus is performed pre-operatively and decompression of the dilated colon of non-obstructive colonic ileus is now regularly achieved. Colonic strictures have been dilated with a variety of techniques ranging from divulsion with through-the-scope balloon dilators to laser recanalization. Pre operative endoscopic laser relief of tumor obstruction is employed to avoid preliminary or decompressing colostomy. Endoscopic laser debulking and recanalization of recurrent or inoperable cancer has been achieved with up to 80% success and various foreign bodies may be extracted from the colon with a number of endoscopic techniques. The morbidity of therapeutic colonoscopy has ranged from 1% to 2% for polypectomy to 11% for laser palliation of bleeding from advanced cancer, often with obstruction. PMID- 1455875 TI - Endoscopic therapy for biliary obstruction. AB - Endoscopic management of biliary obstruction is feasible in most patients and has emerged as standard treatment. Aside from the removal of bile duct stones, placement of a biliary stent is the most commonly employed modality of management. In experienced hands, this is successful in over 90% of patients. Lower procedure-related complications and the relative non-invasive nature of endoscopic treatment has relegated surgical management to a subsidiary role. Hospitalization time rarely exceeds 1-2 days. In most patients with advanced malignant disease and short life expectancy, stenting affords effective palliation. For the majority of patients endoscopic management is preferable to the percutaneous transhepatic approach due to lower overall mortality and morbidity. Stent occlusion necessitating replacement remains a problem, but improvements in this area can be expected. New plastic stent designs are undergoing investigation. Expandable metallic stents are promising but controlled comparative trials with conventional plastic prostheses are needed. Use of expandable stents should be judicious since these cannot be removed. In the future we can look forward to advances in peroral cholangioscopic technology which may permit targeted treatment of intraductal biliary malignancies. PMID- 1455876 TI - Laparoscopic cholecystectomy: the state of the art. A report on 700 consecutive cases. AB - Born in secret in 1987, developed in an atmosphere of skepticism and even hostility throughout 1988, the laparoscopic cholecystectomy triumphed in 1989-90 and caused a veritable revolution in the world of general surgery. The 700 consecutive cases that we report here reflect the spirit of these various periods. From prudently restrictive, our indications widened to include 90% of all patients with gallbladder lithiasis. Sclero-atrophic gallbladders constitute the greatest challenge for endoscopic maneuvers. This group of patients should be treated by the most experienced operators only. The figures for mortality (0.1%) and complications (3%) are very comparable and even better than those for traditional cholecystectomy. The quality of recovery is infinitely better; there is absence of pain, a short period of hospitalization, return to normal physical activity within 10 days, rapid return to work, and total preservation of the abdominal muscles for participation in sports activities. All these advantages are assets of the laparoscopic cholecystectomy which are not available to the 6% of patients for whom an intra-operative conversion to open surgery is necessary. These patients recover within the conditions of a traditional cholecystectomy which are far from being poor. The large multicenter studies, such as those carried out in France and Belgium recently involving 3,708 patients, arrive at identical conclusions. The laparoscopic cholecystectomy is on its way to becoming the gold standard of treatment for gallbladder lithiasis. It is the first successful step towards surgical techniques of the 21st century which will be carried out inside the musculo-cutaneous envelope of the unopened human body. PMID- 1455877 TI - Laparoscopy in the emergency setting. AB - Laparoscopy has been available for 90 years and was actively undertaken by the gynecologists. Today the vast majority of gynecological procedures are performed by this route. Despite the efforts of a few enthusiastic surgeons, the general surgical community did not incorporate laparoscopy into their armamentarium until the advent of laparoscopic cholecystectomy. However, this endoscopic technique has much to contribute, especially in the setting of emergency care. It is of value in formulating a treatment algorithm and in avoiding unnecessary laparotomy in both blunt and penetrating trauma. Laparoscopy helps to define the nature of obscure abdominal diagnoses, avoids unnecessary appendectomy, and provides the window of opportunity for surgery in mesenteric ischemia due to either arterial or venous thrombosis or embolus. It is also of value in patients with pain or fever of unknown origin, displaced gastrostomy or dialysis tubes, and in the rare patient with gastrointestinal bleeding where other diagnostic modalities have been unable to yield the diagnosis. In this article the instrumentation and techniques will be outlined and the role of laparoscopy in each of the above situations will be detailed. As with all surgical procedures, it is vital that the surgeon be well-trained and knowledgeable about the correct use of the technique, its possible pitfalls and how to avoid them, as well as knowing the contraindications. PMID- 1455879 TI - Endosonography in patient selection for surgical treatment of esophageal carcinoma. AB - A prospective study was carried out to examine the usefulness of endosonography (ES) in the pre-operative staging of patients with carcinoma of the esophagus, and its relevance in predicting resectability and the type of resection. The results of ES were compared with staging by conventional pre-operative methods and with operative staging according to the new American Joint Commission of Cancer staging classification. Of the 89 patients studied, 62 had a resection, 22 a bypass operation, and 5 had no operation. ES examination was unsuccessful in 19 patients because of complete or near complete tumor obliteration of the esophageal lumen and was incomplete in 13 patients because of distal tumor obstruction. These 32 patients accounted for 36% of all ES examinations, 27% of resection group, 55% of bypass group, and 60% of no operation group. The 45 patients who had a satisfactory ES examination and who had underwent a transthoracic resection were analyzed. The sensitivity and specificity of ES in detecting the depth of esophageal involvement were 89% and 96%, respectively, and for lymph node metastasis were 85% and 86%, respectively. However, ES was neither sensitive in detecting extra-esophageal infiltration to mediastinal organs nor was it able to determine the extent of intra-abdominal spread. The accuracy of pre-operative staging was 82% by ES compared with 51% by conventional staging (p < 0.001). ES correctly identified more advanced stage of disease in 14 (31%) patients as compared with conventional staging. On the evaluation of resectability, which was based on conventional investigations without ES, the result was unaffected even if the additional findings of ES were available.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455878 TI - The spectrum of laparoscopic surgery. AB - Laparoscopic procedures have begun to replace many conventional operations because of the avoidance of major surgery and the rapid recovery of the patient. The majority of these traditional operations will be performed laparoscopically in the future. For example, patients who suffer from achalasia will be able to undergo laparoscopic cardiomyotomy and patients with non-cardiac chest pain of esophageal origin will be able to undergo thoracoscopic myotomy. Likewise, a viable alternative to long-term medication with H2 blockers or omeprazole will be laparoscopic posterior vagotomy and anterior lesser curve seromyotomy. As methods are developed to deal with the extraction of large specimens, many ablative procedures will be undertaken by the laparoscopic route. Extraction techniques must not compromise the need for histopathological examination of the resected specimen in cancer resections. The ultimate spectrum of laparoscopic surgery will be determined by the progress in remote handling technology, overcoming the manipulative restrictions inherent in the current instrumentation. Research evaluating the efficacy of new methods will be essential. PMID- 1455880 TI - Pre-operative radiotherapy prolongs survival in operable esophageal carcinoma: a randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer. AB - In a prospective multicenter study, 186 patients with squamous cell esophageal carcinoma, who after evaluation were considered suitable for surgery, were randomized to 4 treatment groups: Group 1, surgery alone; Group 2, pre-operative chemotherapy (cisplatin and bleomycin) and surgery; Group 3, pre-operative irradiation (35 Gy) and surgery; Group 4, pre-operative chemotherapy, radiotherapy, and surgery. Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy. Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival. Female patients had a significantly better survival than males. The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival, whereas the chemotherapy regime used did not influence survival. PMID- 1455881 TI - Gastrointestinal motility of patients with Roux-en-Y reconstruction. AB - The electromyographic activity of the gastrointestinal tract was studied in 28 patients undergoing gastric, biliary, and pancreatic operations with reconstruction of the gastrointestinal tract with a Roux-en-Y limb. The Roux-en-Y limb was constructed 1 to 5 years before the study in 8 patients (chronic Roux-en Y) and at the operation in which the electrodes were implanted in 20 patients (recent Roux-en-Y). All four phases of the migrating motor complex (MMC) were identified in the gastrointestinal tract, including in the Roux-en-Y limb. The duration of the MMC was 82.4 +/- 22.3 min in the patients with chronic Roux-en-Y and 89.0 +/- 25.1 min in the patients with recent Roux-en-Y. Food ingestion converted the MMC to the fed pattern in the entire gastrointestinal tract, including the Roux-en-Y limb in 16 (76.2%) of 21 recordings of the patients with chronic Roux-en-Y and in 27 (84.4%) of 32 recordings of the patients with recent Roux-en-Y. The duration of the fed pattern was 170 +/- 34 min in the patients with chronic Roux-en-Y and 154 +/- 26 min in the patients with recent Roux-en-Y. The findings of this study indicate that the electromyographic activity of the Roux-en-Y limb is normal during both fasting and fed states, even many years after the construction of the Roux-en-Y. PMID- 1455882 TI - Optimization of isolated hyperthermic limb perfusion. AB - During isolated limb perfusion, we studied the impact of limb temperature on the concentration of cytostatic drugs in the tissue to identify a possible selective absorption of cytostatic agents by the various tissues. Ten consecutive patients with malignant melanoma were randomly divided into two different groups and perfused with 1 mg cisplatin per kg body weight. In one group the cytostatic agents were injected under hyperthermic conditions (39.5 degrees C) and in the other group under normothermic conditions (37 degrees C). The platinum concentration in the melanoma was twice as high in the hyperthermic group as in the group under normothermic conditions. In the tumor-free tissue the platinum concentration decreased with temperature while it remained constant in the musculature. This selective concentration of cisplatin in the tumor under hyperthermic conditions is accompanied by fewer side effects. Follow-up will show whether the oncological results will be improved in the hyperthermic conditions as one might expect. PMID- 1455883 TI - The effects of positive airway pressure and intra-abdominal pressure in diaphragmatic rupture. AB - Arterial blood gases (80% oxygen), intraperitoneal pressure (IP), stomach position relative to the diaphragm (S/D by fluoroscopy), blood pressure, and cardiac output were monitored in 16 anaesthetized New Hampshire piglets with a 12 cm laceration of the left hemidiaphragm. Group I (8 animals) were spontaneously breathing. Group II (8 animals) had a pneumatic antishock garment (PASG) inflated to an IP of 40 torr for 15 mins followed by positive pressure ventilation (PPV) of 20 cm H2O for 15 min and PPV of 40 cm H2O (PPV-40) for 30 more minutes. All Group I animals survived. Three Group II animals died by 15 min after PASG inflation. Seven Group I animals showed no displacement of the stomach above the diaphragm. Blood pressure, cardiac output, and blood gases remained unchanged in Group I compared to baseline with pO2 varying from 436 +/- 44 torr to 417 +/- 31 torr, pCO2 from 38 +/- 1 torr to 39 +/- 1 torr, and pH 7.4 +/- 0.02. Blood pressure in Group I was 109 +/- 3 torr at baseline to 110 +/- 2 torr at 60 mins, and baseline cardiac output was 3.9 +/- 0.2 L/min and 3.8 +/- 0.2 L/min at 60 min. Group II animals had a baseline arterial pO2 of 423 +/- 15 torr and 100 +/- 15 torr at 15 min after PASG. With PPV-20 arterial pO2 increased to 178 +/- 13 torr and further increased to 230 +/- 9 torr at PPV-40.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455884 TI - Long-term functional results and quality of life after ileal pouch-anal anastomosis and cholecystectomy. AB - Among 971 patients with chronic ulcerative colitis who underwent ileal-pouch anal anastomosis during an 8-year period from January, 1982 to December 1989, 30 patients were randomly selected from each year (total = 240 patients) for an assessment of their long-term functional results and quality of life as of 1990. Patients undergoing cholecystectomy during each of the same years served as "controls" (20 patients/year, total = 160 patients). All 400 patients completed a written questionnaire that measured bowel habits, overall quality of life, general health, and performance in sports/recreation, travel, sex life, family relationship, occupational work, social activities, and household activities. Ileo-anal patients had more frequent stools (median, 6 stools/day) and more fecal spotting (68% of patients had episodes) than cholecystectomy patients (median, 1 stool/day, 13% had episodes, p < 0.05). In spite of the altered bowel habits, 90% of ileo-anal patients had an excellent overall quality of life, 76% enjoyed good health, and 91% had good performance scores in the areas examined. In fact, quality of life and performance were similar among ileo-anal patients and cholecystectomy patients. Moreover, quality of life and bowel habits remained steady in both groups of patients during the 8-year follow-up. In conclusion, functional results were satisfactory and quality of life was excellent after ileal pouch-anal anastomosis; neither deteriorated as patients aged over an 8 year period after operation. PMID- 1455885 TI - Routine versus selective intra-operative cholangiography during laparoscopic cholecystectomy. AB - Opinion is divided whether intra-operative cholangiography should be performed routinely or on a selective basis during laparoscopic cholecystectomy. We therefore performed the first prospective randomized trial of static cholangiography in patients who did not have indications for cholangiograms. Laparoscopic cholecystectomy was attempted on 164 consecutive patients, of whom 49 (30%) patients were excluded from the trial due to indications for or against cholangiography. In the remaining 115 (70%) patients, 56 were randomized to the cholangiography group while 59 patients did not receive cholangiograms. Duration of postoperative hospitalization and interval to return to full activity were identical in the two groups. Static cholangiograms added 16 +/- 1 min (mean +/- SEM) to the procedures (p < 0.01). Cholangiography increased the total charges for the operation by almost $700 (p < 0.01). Cholangiograms were performed successfully in 94.6% of the patients and changed the operative management in 4 (7.5%) patients. There was 1 (1.9%) false negative study. Intra-operative cholangiography did not reveal aberrant bile ducts at risk of injury from the operative dissection. There was no mortality or cholangiogram-related morbidity in either group. In follow-up ranging from 2-12 months, there has been no clinical evidence of bile duct injury or retained common bile duct stones. In summary, in patients without indications for cholangiography, the performance of static cholangiograms markedly increased the operative time and cost of laparoscopic cholecystectomy. The operative management of a minority of patients was changed by the information obtained, but laparoscopic cholecystectomy may be performed safely in the absence of cholangiograms with little risk of injury to the major ductal system or retained calculi. PMID- 1455886 TI - Prostacyclin release from the human saphenous vein in diabetics in lower than in nondiabetics. AB - The balance between prostacyclin and thromboxane has been suggested to be of great importance for the maintenance of patency in veins. In order to investigate prostacyclin and thromboxane release, segments from the human saphenous veins were investigated in 53 patients. Twenty-seven patients (10 males, 17 females) underwent surgery for varicose veins. Twenty-six patients (14 nondiabetics, 12 diabetics) underwent surgery for lower limb ischemia (rest pain or gangrene) with use of the saphenous vein as arterial conduit. Vein segments were gently excised and perfused ex vivo for five 15 minute periods, with a balanced salt solution and determination of the stable degradation products 6-keto-PGF1 alpha and TxB2. Saphenous veins from patients with varicose veins had an initial prostacyclin release of 61 +/- 13 pg/mm2/15 min declining to 4 +/- 1 pg/mm2/15 min after 60 min (p < 0.001) and increasing after addition to arachidonic acid to 37 +/- 7 pg/mm2/15 min (p < 0.001). Segments from nondiabetic patients with lower limb ischemia did not differ from those of varicectomy patients, but diabetic segments had a significantly lower prostacyclin release than both these groups, 34 +/- 11 pg/mm2/15 min, 1 +/- 1 pg/mm2/15 min, and 7 +/- 5 pg/mm2/15 min, respectively (p < 0.05). The addition of arachidonic acid failed to increase the prostacyclin release in diabetics. Three patients from each group were studied regarding thromboxane release and there was almost no detectable thromboxane in any group. These findings suggest that diabetics have a lowered prostacyclin release from the saphenous vein and that the deficiency is at the cyclo-oxygenase level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455887 TI - Bleeding varices of the small bowel as a complication of pancreatitis: case report and review of the literature. AB - A case of a 48 year old male with a history of alcohol abuse, chronic relapsing pancreatitis, and massive hemorrhage into the small intestine is reported. The patient had previously undergone a cholecystojejunostomy. Imaging studies demonstrated occlusion of the splenic, superior mesenteric, and distal portal veins with large varices in the jejunum. He recovered following jejunal resection and Roux-en-Y cholecystojejunostomy. The mechanism for formation of varices in the small bowel in this clinical setting is discussed. PMID- 1455888 TI - Thromboembolic complications in thermally injured patients. AB - The frequency of thromboembolic complications in burn patients has been estimated to range from 0.4% to 7%. The clinical significance of these events is often debated and has prompted some centers to adopt the routine prophylactic use of low dose heparin prophylaxis. A 10 year review of 2,103 burn patients treated at this institution was undertaken. Twenty-five (1.2%) patients, with a mean age of 40.0 years and an average burn size of 49.3% total body surface area (TBSA), were identified as having significant pulmonary thromboembolism (PTE). In only 3 (0.14%) patients was the thromboembolism considered to be a cause of death. Nineteen (0.9%) patients, with an average age of 36.7 years and a mean burn size of 48.3% TBSA, developed clinically evident deep venous thrombosis (DVT); however, in only 1 (0.05%) patient did the disease progress to fatal PTE. A review of the literature reveals a 0.6% to 5% incidence of complications related to low dose heparin therapy which includes bleeding, thrombocytopenia, and arterial thrombosis. We feel that the infrequency of clinically significant PTE and DVT in burn patients and the comparable or greater rate of complications associated with heparin prophylaxis mitigate against the routine use of low dose heparin therapy except in patients at high risk for these events. PMID- 1455889 TI - Injury to the popliteal vessels: the Lebanese war experience. AB - Our experience with 118 patients who underwent surgery for a total of 178 popliteal vessels injuries is reported. Forty-nine per cent had injury to both artery and vein and 44% had associated bony fractures. Fourteen patients subsequently needed amputation for a rate of 11.9%. There were no deaths. Delay in repair (> 6 hours from injury), associated fractures, and a shocked condition resulted in increased limb loss. Arterial as well as venous repair, external skeletal fixation, and fasciotomy when necessary lead to improved limb salvage. PMID- 1455890 TI - Acute acalculous cholecystitis complicating trauma: a prospective sonographic study. AB - Acute acalculous cholecystitis (AAC) is a well known complication in severely traumatized patients. Existing data of AAC originate from retrospective analyses and episodic case reports. In a prospective study 45 polytraumatized patients admitted to our intensive care unit from January 1989 to June 1990 were clinically and sonographically screened for this condition at defined time intervals. Trauma scoring was performed according to the injury severity score and polytrauma score. AAC was defined as a combination of hydrops of the gallbladder, an increased wall thickness (> 3.5 mm), and the demonstration of sludge. We were able to document this diagnostic triad in 8 (18%) of 45 patients. As a consequence early elective cholecystectomy was performed in 1 of the 8 patients. The remaining patients were treated conservatively. The incidence of AAC in severely traumatized patients is higher than figures so far published suggest. Ultrasound is a reliable method of early detection and follow-up of this complication. PMID- 1455891 TI - One liver for two: partition of the portal elements. AB - A cadaver liver is divisible into two transplants by section between right and left lobes, or section between left medial segment and left lateral segment medial to the umbilical cleft. To establish the ideal basis of partition of the portal elements, an anatomic study of 33 livers was performed. It is preferable to section the left portal vein, longer and more constant than the right, the right branch of the hepatic artery, larger and more constant than the left, and the left hepatic duct because of the vascularization of the common hepatic duct. To use the length of the left portal vein, it is necessary to section all its branches to segment I and then to resect this segment. After a section between the left medial segment and the left lateral segment medial to the umbilical cleft, the left medial segment always loses its total portal venous vascularization and should be resected. Before a split-liver, cholangiography and arteriography should be performed to detect anatomical variations without performing an extensive dissection which may endanger the vascularity of the bile ducts. PMID- 1455892 TI - Roux-en-Y hepaticojejunostomy with subcutaneous access and the use of Gianturco stents for the management of biliary tract strictures. AB - The need to control recurrent biliary strictures implies the practice of repeated major surgical procedures. The hepaticojejunostomy with subcutaneous jejunal access (Chen's procedure) allows the permanent option of a non-operative management of recurrent biliary tract anastomosis complications. Through the subcutaneous jejunal access, the application of a Gianturco metallic prosthesis is permitted and the correction of biliary-intestinal anastomosis strictures with non-operative methods is possible. This report is a review of a series of 20 patients treated with the Chen procedure, of whom 3 patients also had implantation of Gianturco stents via hepaticojejunostomy with subcutaneous access. PMID- 1455893 TI - Living unrelated donor kidney transplantation between spouses. AB - From November 3, 1975 to November 3, 1990, 874 kidney transplants were performed at out centers. Of these, 675 (77.2%) were from living donors and 199 (22.8%) were from cadaver donors. Five hundred eighty (66.4%) of the living donors were first degree related while 99 (11.3%) were unrelated or second degree related donors, 29 of which were spouses. All donor recipient pairs were ABO-compatible, with the exception of one pair. Donor recipient relations were wife to husband in 25 cases and husband to wife in 4 cases. All were first grafts and started functioning during surgery. In this series, the follow-up for the recipients was 4 to 64 months (mean 33.5 +/- 4.5 months). One-year patient survival and graft survival rates were 92.4% and 81.9%, respectively. Two-year patient survival and graft survival rates were 92.4% and 78.2%, respectively. The single ABO incompatible case is also doing well, 21 months postoperatively. This study demonstrates that the interspouse kidney transplantation may be used when cadaver organ shortage is a problem. While providing the couple with a better quality of life, interspouse kidney transplantation also enables the couple to share the joy of giving and receiving the "gift of life" from one another. PMID- 1455895 TI - The Drug Metabolism Discussion Group 1991. PMID- 1455894 TI - Present status of sclerotherapy and surgical treatment for esophageal varices in Japan. Japanese Research Society for Portal Hypertension and Japanese Research Society for Sclerotherapy of Esophageal Varices. AB - A nationwide survey on the treatment for esophageal varices was performed in 1990 jointly by the Japanese Research Society for Portal Hypertension and the Japanese Research Society for Sclerotherapy of Esophageal Varices to clarify the present status and strategy of this treatment in Japan. A total of 12,675 cases, including 4,159 cases of nonshunting procedures and 7,612 cases of sclerotherapy, were collected from 101 institutions. The number of patients had greatly increased in the first half of the 1980s. With regard to the therapeutic strategy, surgical procedures were not recommended in either emergency or prophylactic cases in terms of the timing of the operation, or in Child C cases in terms of the degree of hepatic insufficiency. Endoscopic injection sclerotherapy became the leading method of treatment and in 1988 only 16% of 1,528 cases were treated by surgical procedures. The strategy for the same group of patients differed between medical and surgical institutions. With regard to sclerotherapy, repeated intravariceal injection and combined intra- and paravariceal injection were the two main techniques and 10-year cumulative survival rates were 62.8% in Child A cases, 47.7% in Child B cases, and 13.2% in Child C cases. With regard to surgical procedures, 10-year survival rates were 50.6% in esophageal transection, 42.5% in gastric transection, 53.1% in cardiectomy, and 43.0% in selective shunt procedures. We are quite convinced that this report will prove useful in determining the future strategy for treating esophageal varices. PMID- 1455896 TI - Special issue: Drug Metabolism Discussion Group 1991. PMID- 1455897 TI - Comment. Twenty years on: a review of the current practice of drug metabolism and pharmacokinetic studies in the pharmaceutical industry. PMID- 1455898 TI - Role of metabolism and pharmacokinetic studies in the discovery of new drugs- present and future perspectives. AB - 1. The impact which pharmacokinetics and drug metabolism studies have made to drug discovery programmes is reviewed with examples from the anti-infective, cardiovascular, anti-inflammatory and CNS therapeutic areas. 2. Contributions that advances in analytical technology have made to the early application of pharmacokinetics and drug metabolism are discussed. 3. Some future perspectives are given on the advances being made in basic science and technology and how this will provide the basis for further growth in the contribution to the drug discovery process. PMID- 1455899 TI - Drug analysis of biological samples. A survey of validation approaches in chromatography in the UK pharmaceutical industry. AB - 1. The results of a survey on validation of analytical chromatographic methods are reported. The survey was carried out in 1990 within most of the principal British Pharmaceutical Companies. 2. A general method of validation is established from the collated results. 3. A comparison is made with existing reports from international meetings. PMID- 1455900 TI - Application of 19F-n.m.r. spectroscopy to the identification of dog urinary metabolites of imirestat, a spirohydantoin aldose reductase inhibitor. AB - 1. Urine from a dog dosed orally at 20 mg/kg with 14C-imirestat, a spirohydantoin aldose reductase inhibitor, contained 17.7 and 12.5% of the administered radioactivity at 0-48 and 48-72 h respectively. 2. Radio-h.p.l.c. of the 0-48 h urine revealed a complex mixture of metabolites and a small proportion of parent drug (1.6% of dose). Direct 19F-n.m.r. spectroscopy of this urine showed the fluoride ion, numerous metabolites which were predominantly glucuronide conjugates and, as a minor component, the parent drug. 3. After incubation with beta-glucuronidase the 0-48 h urine gave a 19F-n.m.r. spectrum showing fewer signals. This finding is consistent with aromatic ring hydroxylation followed by glucuronidation being the major metabolite pathways. 4. Deconjugated urine was analysed by proton-coupled 19F-n.m.r. and two-dimensional 19F-19F correlated spectroscopy. Results indicate that major components included three monohydroxy metabolites, a diphenol with both phenolic functions in the same ring, and a phenolic metabolite containing only one fluorine atom. 5. Semi-preparative h.p.l.c. of 0-48 h dog urine gave individual glucuronides isolated as mixtures of C-9 epimers. These fractions were hydrolysed and purified a second time by h.p.l.c. to give aglycones which were analysed by multi-nuclear n.m.r. and g.l.c. mass spectrometry. The 3- and 4-hydroxy derivatives of imirestat were identified, as was the 2-hydroxy product obtained during or following defluorination. The other major aglycone was postulated to be the 3-fluoro-2-hydroxy metabolite. This represents a novel 'NIH-shift' type pathway for the metabolism of fluorobenzenes. PMID- 1455901 TI - Disposition of the enantiomers of cromakalim in rat and cynomolgus monkey. AB - 1. Disposition of the 3R,4S(+) and 3S,4R(-) enantiomers of the racemic antihypertensive drug cromakalim has been studied in rats and cynomolgus monkeys using the 14C-drug labelled in either the 3R,4S(+) or the 3S,4R(-) enantiomer. 2. After oral administration to rat, blood concentrations of the 3R,4S(+) enantiomer were up to fourfold higher than those of the 3S,4R(-) enantiomer. Metabolism of the former was not as extensive as that of the latter and consequently plasma and urinary radiometabolite patterns were quantitatively different. 3. In contrast to rat, there were much greater differences in the disposition of the two enantiomers following oral administration of cromakalim to the cynomolgus monkey. Plasma concentrations of the 3R,4S(+) enantiomer were approximately 100 x those of the 3S,4R(-) enantiomer and the rate of urinary 14C elimination for the 3R,4S(+) enantiomer was much faster than that for the 3S,4R(-) enantiomer. Plasma and urinary radiometabolite patterns were very different for the two isomers. Metabolic end products of the 3R,4S(+) enantiomer were predominantly phase I metabolites whereas the 3S,4R(-) enantiomer was almost entirely metabolized by glucuronidation. 4. A study of the racemic drug alone would have led to a misunderstanding of the fate of the compound in these species. PMID- 1455902 TI - Comparative metabolism of flunarizine in rats, dogs and man: an in vitro study with subcellular liver fractions and isolated hepatocytes. AB - 1. The biotransformation of 3H-flunarizine ((E)-1-[bis(4-fluorophenyl)methyl]-4 (3-phenyl-2-propenyl)piperazine dihydrochloride, FLUN) was studied in subcellular liver fractions (microsomes and 12,000 g fraction) and in suspensions or primary cell cultures of isolated hepatocytes of rats, dogs and man. The major in vitro metabolites were characterized by h.p.l.c. co-chromatography and/or by mass spectrometric analysis. 2. The kinetics of FLUN metabolism was studied in microsomes of dog and man. The metabolism followed linear Michaelis-Menten kinetics over the concentration range 0.1-20 microM FLUN. 3. A striking sex difference was observed for the in vitro metabolism of FLUN in rat. In male rats, oxidative N-dealkylation at one of the piperazine nitrogens, resulting in bis(4 fluorophenyl) methanol, was a major metabolic pathway, whereas aromatic hydroxylation at the phenyl of the cinnamyl moiety, resulting in hydroxy-FLUN, was a major metabolic pathway in female rats. In incubates with hepatocytes, these two metabolites were converted to the corresponding glucuronides. 4. In human subcellular fractions, aromatic hydroxylation to hydroxy-FLUN was the major metabolic pathway. In primary cell cultures of human hepatocytes, oxidative N dealkylation at the 1- and 4-piperazine nitrogen and glucuronidation of bis(4 fluorophenyl)methanol were observed. The in vitro metabolism of FLUN in humans, resembled more than in female rats and in dogs than that in male rats. 5. The present in vitro results are compared with data of previous in vivo studies in rats and dogs. The use of subcellular fractions and/or isolated hepatocytes for the study of species differences in the biotransformation of xenobiotics is discussed. PMID- 1455903 TI - Metabolism of calcium antagonist Ro 40-5967: a case history of the use of diode array u.v. spectroscopy and thermospray-mass spectrometry in the elucidation of a complex metabolic pathway. AB - 1. The calcium antagonist, Ro 40-5967, is metabolized to a multitude of products by the rat and drug-related material is excreted predominantly via the bile. 2. Diode-array u.v. spectroscopy, following reverse phase h.p.l.c. separation of the partially purified metabolites, has been used to classify these compounds into six spectral classes which have been correlated with different metabolic reactions. 3. Connection of a mass spectrometer directly to the h.p.l.c. equipment by a thermospray interface, produced useful mass spectra. These, together with the u.v. spectra, enabled the structures of many metabolites to be elucidated. 4. Confirmation of structural assignments was provided by n.m.r. spectra of the major metabolites. 5. Major metabolic pathways included N demethylation (16% of the biliary metabolites), hydrolysis of the ester side chain (32%), hydroxylation at 4- (19%) and 5- (29%) positions of the benzimidazole ring, aromatization of the tetrahydronaphthyl system (26%), loss of the benzimidazole (15%) and glucuronidation of hydroxyl groups (81%). PMID- 1455904 TI - Measurement of oxybutynin and its N-desethyl metabolite in plasma, and its application to pharmacokinetic studies in young, elderly and frail elderly volunteers. AB - 1. A quantitative h.p.l.c. plasma assay for oxybutynin (OB) and its active metabolite, N-desethyl oxybutynin (DEOB) is described. The method is linear with coefficients of variation ranging between 4 and 11.8% for OB and 4.6-9.1% for DEOB over the typical concentration range measured. Minimum detectable levels were 0.5 and 5 ng/ml for OB and DEOB respectively from a 2 ml sample. 2. Pharmacokinetic parameters were obtained after a single oral dose of OB and after administration two or three times daily to frail elderly and elderly volunteer groups respectively. Single dose results were also compared with data from young healthy volunteers. 3. There was a wide range in peak blood levels and high levels of parent drug were matched by high DEOB metabolite levels. Plasma levels on repeated administration were as would be predicted from the single dose kinetics. 4. Area under the plasma time course curve for DEOB metabolite was less than or equal to 5 than that of the parent drug. 5. A trend of increasing peak plasma levels and bioavailability was observed with increasing age and frailty, with the differences more apparent between the active elderly and frail elderly groups than between the active elderly and young volunteers. 6. Results indicate that for frail elderly patients a lower initial starting dose of 2.5 mg OB given two or three times a day may provide adequate therapeutic blood levels of the drug. PMID- 1455905 TI - Value of early pharmacodynamic and pharmacokinetic investigations with anticancer drugs: data from phase I tolerance studies on a new vinca alkaloid derivative. AB - 1. A novel anticancer vinca alkaloid derivative (I) has been given as an i.v. bolus to cancer patients, using four different dosage regimens with dose levels ranging from 0.04 to 0.84 mg/m2 (equivalent to between 0.12 and 1.35 mg per dose), and the pharmacokinetics determined up to 72 h after dosing. In addition, secondary effects of leukopenia and neutropenia, were related to drug exposure using a sigmoid Emax model. 2. Plasma levels of I declined in a triphasic manner with a terminal half-life of approximately 50 h; most drug elimination (55%) being associated with the terminal phase. 3. Clearance of I was relatively low (245 +/- 160 ml/min) and remained constant with increasing doses. Initial distribution volume was low (approximately 71) but once distribution was complete, it was comparatively high (327 +/- 2121). 4. Both leukopenia and neutropenia were fitted successfully to a sigmoid Emax model showing that these effects were related to the total exposure to the drug. The Hill constant was less than 1, indicating a relatively shallow exposure/response curve and a predictable, graded increase in response with increasing I exposure, rather than a sudden quantal response. 5. Pharmacokinetically, I shows some similarities to other vinca alkaloids in its plasma level decline profile, although there are some notable differences which can be exploited clinically. In addition, the ability to model both leukopenia and neutropenia to the exposure to I, provides a valuable tool in the design of the most appropriate dosage regimen for the drug, as well as for dose adjustment taking into account inter-individual variations. PMID- 1455906 TI - Statistical aspects of bioequivalence--a review. AB - 1. Over the past 20 years a number of statistical methods have been proposed for use in bioequivalence testing. This review examines these methods and reflects current thinking of regulatory authorities. 2. The standard bioequivalence study is conducted as a controlled, single-dose crossover design in a small number of healthy male adults. Blood and/or urine samples are taken at predetermined times for drug/metabolite assay from which pharmacokinetic parameters are derived and compared statistically. Sample size calculations should be determined by the error variance associated with the primary characteristic to be studied, the significance level, the power of the test and the deviation from the reference product compatible with safety and efficacy. 3. In general, bioequivalence is assessed using three parameters namely, Cmax, tmax and AUC. Urinary excretion data may also be used if the amount excreted unchanged is significant. These parameters are best obtained using a simple model-independent approach. 4. The parameters of Cmax and AUC should be logarithmically transformed prior to analysis. For tmax, parametric statistical procedures are not appropriate. 5. Classical hypothesis testing using the power approach is not applicable to the practical problem under consideration in bioequivalence trials. 6. Classical 90% confidence limits and the 2 one-sided t-test approach are operationally identical and are the methods of choice for assessing bioequivalence (Cmax and AUC). When tmax is an important parameter from the clinical point of view then the use of non-parametric confidence intervals is recommended. PMID- 1455907 TI - Immunomodulatory action of propolis: IV. Prophylactic activity against gram negative infections and adjuvant effect of the water-soluble derivative. AB - The efficacy of the water-soluble derivative (WSD) of natural propolis (bee glue) was examined for augmentation of host resistance against experimental infections caused by Gram-negative pathogens (Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa). The substance was found to induce significant non-specific protection, but did not inhibit the in vitro growth of the same strains. Pretreatment with WSD prior to the standard scheme for tumour necrosis factor (TNF) induction (BCG and two weeks later lipopolysaccharide (LPS)) provoked an interval-dependent reduction in the lytic capacity of serum against L 929 target cells. The replacement of the triggering or priming signal with WSD markedly increased TNF production. In vivo administration of WSD led to a rapid and route-dependent change in the alternative complement pathway haemolysis. The alteration in C1q complement component and total protein synthesis, and also in nitroblue tetrazolium reduction, suggests that macrophage activation makes a major contribution to the capacity of WSD to prevent infections. PMID- 1455909 TI - Immunogenicity of a Streptococcus pneumoniae type 4 polysaccharide--protein conjugate vaccine is decreased by admixture of high doses of free saccharide. AB - In this study we report that the priming capacity of a Streptococcus pneumoniae type 4 polysaccharide-protein conjugate to booster immunizations with the native capsular polysaccharide is dose dependent. Furthermore, it is shown by admixture experiments that simultaneous administration of high doses of free saccharide (0.5-25 micrograms) of different chain lengths (varying from M(r) 1.6-120 kDa) decreases the anti-polysaccharide antibody response. Presence of low doses of saccharide (up to 10%), which are usually present in conjugates prepared by the carbodiimide coupling procedure, did not influence the anti-polysaccharide antibody response in adult and neonatal mice. PMID- 1455908 TI - Nasal antibody response to mumps virus after vaccination and natural infection. AB - Nasopharyngeal secretions and sera were collected during an epidemic of mumps in a semi-closed institution. None of the children who received live attenuated mumps vaccine 5 months previously developed any symptoms of mumps. Neutralizing and IgA antibodies against mumps virus were measured by the peroxidase antiperoxidase method and the fluorescent antibody to membrane antigen method, respectively. The immune responses in nasopharyngeal secretions and serum were studied in four groups (apparently infected, non-apparently infected, non infected and vaccinated). We found that IgA, which has neutralizing activity, was produced after vaccination as well as after natural infection. It is suggested that local antibody induced by vaccination may contribute to protection against the mumps virus. PMID- 1455910 TI - Safety and immunogenicity in volunteers of a recombinant Plasmodium falciparum circumsporozoite protein malaria vaccine produced in Lepidopteran cells. AB - A recombinant Plasmodium falciparum circumsporozoite (CS) antigen (rPfCSA) was produced in insect cells using a baculovirus expression vector containing the entire CS gene. This near full-length CS antigen was adsorbed onto aluminium phosphate for use as a malaria vaccine. In a study of safety and immunogenicity, 20 volunteers were divided into four groups of five each and inoculated intramuscularly with 10, 100, 500 or 1000 micrograms of vaccine. Primary vaccinations were followed by two booster immunizations at 2 and 6 months. Three volunteers developed prominent local reactions manifested as tenderness, redness and swelling at the injection site following the second or third vaccination. All symptoms resolved spontaneously within 72 h. Postimmunization sera from six of 20 volunteers showed seroconversions as measured by Western blot, using rPfCSA as antigen. However, specific anti-CS protein antibody could not be detected by indirect immunoflourescence against intact sporozoites or by ELISA using rPfCSA or peptide to the repeat region. In addition, 18 of 20 volunteers developed antibody to baculovirus proteins as determined by ELISA and/or Western blot. Antigen-driven replication studies using peripheral blood mononuclear cells from vaccinees failed to detect proliferative responses specific to CS protein. This recombinant CS protein vaccine, as formulated, was minimally immunogenic in humans. PMID- 1455911 TI - Impaired response to hepatitis B vaccine in HIV infected children. AB - Eighteen human immunodeficiency virus (HIV) vertically infected children (HIV group) and 33 seroreverted children (SR group), who had completed hepatitis B vaccination (Engerix B, 20 micrograms dose) were studied. Four out of 18 (22%) HIV children failed to develop protective antibody levels (anti-HBs titres less than 10 mIU ml-1) compared with 1 out of 33 (3%) SR children (p less than 0.05). Magnitude of response among HIV children was significantly lower than among SR children. In HIV children the probability that anti-HBs titres persist above the protective levels was significantly lower than in the SR group at any time during the 24 month follow-up. These results show that HIV children have a suboptimal response to hepatitis B immunization and the protection is less durable. Further studies are needed to determine the optimal protocol for hepatitis B immunization in HIV children. PMID- 1455912 TI - Antigenic characterization of the live attenuated Japanese encephalitis vaccine virus SA14-14-2: a comparison with isolates of the virus covering a wide geographic area. AB - In China, a live attenuated Japanese encephalitis (JE) vaccine, based on strain SA14-14-2, has been derived from the wild-type strain SA14 as an alternative to the current inactivated vaccines such as Nakayama-NIH and P-3. SA14-14-2 has been characterized using monoclonal antibodies derived in mice, using HAI and neutralization tests, and compared with other Chinese live vaccine clones and 14 wild-type strains of JE virus. Wild-type strain SA14 was found to be a poor immunogen and antigenically distant from all other viruses examined. The vaccine derivatives SA14-5-3 was more immunogenic than its wild-type parent, while SA14 14-2 (derived from SA14-5-3) was more immunogenic than SA14-5-3 and elicited a cross neutralizing antibody response. Our studies indicated that JE virus strain Nakayama elicited as good a neutralizing antibody response in hyperimmunized mice as the SA14-14-2 vaccine clones grown in either primary hamster kidney (PHK) or primary dog kidney (PDK) cells. A single dose of live SA14-14-2 (PHK) also elicited a good antibody response. Antigenic variation between wild-type and vaccine clones of JE virus were detected but were not considered significant in terms of controlling JE virus infections by vaccination. PMID- 1455913 TI - Specific and non-specific immunity and protection of macaques against SIV infection. AB - The simian immunodeficiency virus is a retrovirus closely related to the human immunodeficiency viruses; it induces an AIDS-like disease in macaques, and provides therefore an obvious animal model for anti-lentiviral drug and vaccine strategy assessments. In our experiment, we immunized rhesus macaques with a purified and formalin-inactivated whole SIVmac251 antigen preparation. Most of these monkeys were still protected for more than 4 months following a heterologous SIVsm intravenous challenge. Both virus stocks, for vaccine preparation and challenge, were provided by culture supernatants of infected T cells of human origin. Four of the protected macaques were then reimmunized with the same antigen preparation and rechallenged intravenously with a homologous rhesus cell grown SIVmac251. Unexpectedly, all animals developed clinical and biological evidence of infection by day 15 after the second challenge. PMID- 1455914 TI - Endothelins. AB - The endothelins (ET) represent a novel family of at least three isopeptides (ET 1, ET-2, ET-3), each consisting of 21 amino acids and two disulfide bridges. ET has originally been isolated from the supernatant of porcine aortic endothelial cells and has been found to be the most potent and long lasting vasoconstrictor agent yet discovered. ET is synthesized as a preprohormone and cleaved by unusual proteolytic processing. The different isoforms of ET seem to differ in their biological activity which may be due to interaction with different ET-receptor subtypes (ETA, ETB, ETC) and their tissue distribution. Besides its vasoactive properties, ET evokes a variety of other effects, such as positive inotropic and chronotropic actions on the heart, the release of other regulatory substances (EDRF, prostanoids, ANP), as well as cellular mitogenesis. Therefore, the endothelins have been implicated in the pathophysiology of a variety of cardiovascular disorders, however their precise role remains to be elucidated. Such research might have potential application on veterinary medicine learning about factors responsible for vascular damage and consecutively being able to treat or prevent various vascular diseases more specifically. PMID- 1455915 TI - Demonstration of immunoglobulins and complement in canine and feline autoimmune and non-autoimmune skin diseases with the direct immunofluorescence and indirect immunoperoxidase method. AB - Skin sections from 71 dogs and 10 cats with bullous autoimmune skin diseases and various non-autoimmune dermatopathies were studied for the presence of immunoglobulins (canine IgG, IgM, IgA; feline IgG) and complement (canine C3) using the direct immunofluorescence method (DIF) and the indirect immunoperoxidase method (IIP). In cases of autoimmune skin diseases (9 dogs, 3 cats) both methods were of comparable sensitivity for the detection of epidermal deposits. In canine cases with non-autoimmune dermatopathies, epidermal immunoreactivity was found in 16.1% of cases with the DIF method, and in 29.0% of cases with the IIP method. With both methods, epidermal deposits were most frequently seen in skin sections of dogs with bacterial diseases. Furthermore, positive reactions were found in canine cases with hypersensitivity disorders, endocrine dermatosis, dermatomycosis, parasitic disease, cutaneous Leishmaniasis and in cases with non-specific dermatopathies of uncertain aetiology. In the majority of canine cases intercellular deposits of IgG were found. Immunohistological results should always be interpreted in conjunction with clinical and histomorphological findings in order to establish a diagnosis of autoimmune skin disease and to prevent misdiagnoses. PMID- 1455916 TI - Studies on abnormal moulting in the farm-raised blue fox (Alopex lagopus). AB - In a farm-raised, adult female blue fox (Alopex lagopus) it was observed that apparently the winter coat was shed abnormally. Furthermore, the individual was never recorded as being on heat. Comparative histological and clinical-chemical examinations showed that the winter coat cycle was postponed approximately 6 months, and that the hair growth therefore took place in the spring. At first a kind of biological summer coat was produced, and then a biological mature winter coat. This was compared with and partly documented by changes in plasma estradiol and cortisol profiles. It could be concluded that the hair growth cycle and the plasma estradiol profile showed an abnormal seasonal variation in the abnormal fox. The two variables seemed, however, to be correlated as in a normal animal. PMID- 1455917 TI - Blood levels of prostaglandin metabolites (PGFM, PGEM) after parturition in cows with and without retained placenta considering spontaneous calving and dystocia. AB - Blood samples were taken from 71 Holstein Friesian cows at 0, 3, 24 and 48 hours after parturition. Peripheral plasma concentrations of prostaglandin F2 alpha and E2 metabolites (PGFM, PGEM) were determined by radioimmunoassay. The cows were divided into 4 groups, according to type of calving (spontaneous, dystocia) and discharge of placenta. Group 1: spontaneous calving, shedding of placenta within 12 hours (SC, NRP, n = 19); group 2: spontaneous calving, retained placenta (SC, RP, n = 7); group 3: Dystocia, shedding of placenta within 12 hours (Dys, NRP, n = 32); group 4: Dystocia, retained placenta (Dys, RP, n = 13). The PGFM concentrations decreased within 3 hours after parturition only in NRP cows (groups 1 and 3, p < 0.05). Three hours after calving the animals of group 3 had considerably higher PGFM levels than those in group 4 (0.46 +/- 0.26 vs 0.26 +/- 0.11 ng/ml). Significant decreases (p < 0.05) in PGEM concentrations occurred in cows that shed the placenta within 24 hours after parturition. Cows that retained the placenta showed a significant slower decrease of the PGEM levels. It is concluded that postpartum prostaglandin levels are influenced by stress during parturition (dystocia, transportation) as well as by retained placenta. PMID- 1455918 TI - [The effect of the energy intake of cows on the rumen metabolism studied using the excretion of allantoin in milk]. AB - With two groups of dairy cows (A: 12 German Black and White- and 6 German Simmental Cows; B: 16 German Black and White- and 11 German Simmental Cows) allantoin concentrations of blood plasma (A) and milk (A and B) were analysed by HPLC. There exists a close correlation (r = 0.758) between allantoin concentration in blood plasma (370.6 +/- 79.1 mumol/l) and milk (474.1 +/- 78.9 mumol/l). The relation between milk yield and allantoin excretion with milk seems to be non-linear (r = 0.936). On the other hand there is a close correlation between energy intake with feed and allantoin excretion via milk (r = 0.885). In a further experiment the allantoin concentrations in blood plasma of 5 Angler steers were monitored for 24 h every second hour with feeding twice daily. There were remarkable fluctuations in the allantoin concentration from nearly 156 to 129 mumol/l. After that the rumen of the steers was emptied, while plasma concentrations were still monitored the same way as before. Concentrations of allantoin declined for about 55% to 65 mumol/l. PMID- 1455919 TI - [The use of rapid progesterone tests (Serozyme-Progesterone, Ovucheck) for the diagnosis of pregnancy in Austrian mountain sheep]. AB - To determine the oestrous cycle length of mountain sheep 10 ewes were stimulated with intravaginal sponges (Chronogest) and ten with prostaglandins (Iliren) and a PMSG injection (500 IU), respectively. Independent of the synchronisation mode the Serozyme-progesterone levels indicated a cycle length of 17 days. Progesterone was not detectable by the test system during oestrous, it reached its maximum on the 10th day (mean = 3.9/3.7 ng/ml) and decreased to non detectable levels again on day 17. For early pregnancy diagnosis the Serozyme progesterone as well as the Ovucheck gave useful results. On day 17 and 19 after mating the progesterone concentration of pregnant ewes remained on the same level as on day 10, whereas barren ewes had non-detectable progesterone levels on day 17 and 19, using the Serozyme-progesterone and below 1 ng/ml on day 19 using the Ovucheck. The accuracy of the Serozyme-progesterone referring to the declaration "non pregnant" was 100%, that of the Ovucheck 37.5% on day 17 and 100% on day 19. The use of both test systems for determining pregnancy of unknown length was examined by collecting blood-samples three times with a five and a seven day interval. Precise results were obtained only with the Serozyme-progesterone test. At least one of three blood samples of all the barren ewes (n = 8) contained amounts of progesterone beneath the sensitivity of this method. The Ovucheck results could not help at all to distinguish barren or pregnant ewes with unknown mating data. PMID- 1455920 TI - [The acid-base equilibrium in the blood of calves suckled by their mothers and in milk-fattened calves]. AB - The influence of different housing systems on the acid/base balance in the blood of 39 calves in a suckler cow herd of the breeds Deutsche Schwarzbunte and Deutsche Rotbunte, and 25 veal calves of the breeds Deutsche Schwarzbunte and Holstein-Friesian was examined in a period from the first to the sixth month of life. 1. No differences between the test groups were present in the pH of blood. 2. The body temperature was significant higher in calves of the suckler cow herd. 3. Hemoglobin content of the veal calves was significant higher till the third month of life. With increasing age the relations are changed, and at the end of the experimental period significant higher values were found in calves of the suckler cow herd. 4. Marked differences were also present in the carbon dioxide pressure with significant higher values in veal calves. 5. With regard to the metabolic factors of the blood acid/base balance--buffer base, bicarbonate and base deviation--significant higher values were also seen in veal calves. The results are discussed in connection with problems of intensive fattening of calves in comparison to the conditions of calves in suckler cow herds. PMID- 1455921 TI - A comparative study of arterial and venous blood acetate concentration in cows fed different diets close to parturition. AB - Blood samples were collected from the coccygeal artery and a jugular vein two weeks before expected calving, one to five days after calving and three weeks after calving of cows which were fed either a high roughage or a low roughage diet from four weeks before to 14 weeks after calving. The mean venous acetate concentration ranged from about half to three-quarters of the arterial concentration. No differences were observed at any time between concentrations of acetate in either the arterial or venous blood of the cows on the different diets. PMID- 1455922 TI - Hepatic encephalopathy associated with acquired portosystemic shunts in a dog. AB - An 8-month-old dog with a history of gastrointestinal disturbances and neurological signs was presented with hyperammonemia. Necropsy revealed ascites, portosystemic collaterals, and an irregularly surfaced small liver. Histologically, there were diffuse neuronal necrosis and focal spongiform changes in the brain, and marked fibrosis in the liver. Hepatic encephalopathy was diagnosed. PMID- 1455923 TI - Effect of endothelin 1 on plasma glucose and lipid levels in pygmy goats. AB - The effect of endothelin 1, a recently discovered vasoconstrictor hormone, on levels of plasma glucose and lipids was investigated in pygmy goats. Endothelin 1 was injected intraperitoneally (1.72 micrograms/kg BW) and blood samples were taken by puncturing the jugular vein immediately before and 60, 150 and 240 min post injection. Endothelin 1 in comparison to vehicle significantly increased plasma glucose and FFA levels, whereas plasma triglycerides were significantly reduced. Thus, beside its vasoconstrictive action, endothelin 1 also has metabolic effects. Whether these effects are directly caused by endothelin 1 or whether they are due to a release of a metabolic hormone, e.g. epinephrine, remains to be investigated. PMID- 1455924 TI - [The effect of a different energy supply on the growth intensity and skeletal development of growing Great Danes. 2. Effect on insulin-like growth factor I and on thyroid hormones]. AB - In an experiment with 13 growing Great Danes (littermates) fed ad libitum (4 dogs) or restrictively (70% of ad libitum energy intake; 9 dogs), concentrations of insulin-like growth factor I (IGF-I), 3,5,3'-triiodothyronine (T3) and thyroxine (T4) were measured in blood samples until the age of 6 months. In the ad libitum fed group, levels of T3 and T4 were partially and of IGF-I were significantly (p < 0.01) elevated as compared with the control dogs. Postprandial changes of IGF-I were absent in growing Great Danes as well as in a reference group of 3 adult beagles. Increased concentrations of IGF-I, T3 and T4 could be causally related to osteochondrosis, which frequently occurs in intensively fed dogs. PMID- 1455925 TI - Monofrequency oscillation technique in healthy and pneumonic calves younger than 2 months--physiological values and methodological aspects. AB - Using the monofrequency oscillation technique, the oscillatory measured resistance of the respiratory system (Ros) was determined in healthy and pneumonic calves younger than 2 months. Using a face mask, measurements were done in unsedated animals directly in the calfhouse. 106 clinically healthy calves were examined to determine the physiological range of Ros. Calves suffering from pneumonia showed significantly higher values of Ros which were positively correlated with the severity of pneumonic lesions as established by pathological investigations. In healthy calves, the variability of Ros due to biological aspects was found to be much higher than methodologically caused variability. It is concluded that the monofrequency oscillation technique is useful especially in individual investigations, e.g. control of therapy. PMID- 1455926 TI - Renal lesions in Norwegian slaughter pigs. Macroscopic and light microscopic studies. AB - Six hundred and sixty-eight consecutive carcasses of slaughtered swine were examined for renal lesions at meat inspection. The macroscopic lesions were divided into 7 categories: D1 = depressions of the external surface and partial persistence of fetal lobation; D2 = focal leukolymphocytic nephritis (acute focal tubulo-interstitial nephritis); D3 = cysts; D4 = interstitial fibrosis; D5 = infarct-like lesions; D6 = fatty degeneration, and D7 = hydronephrosis. 396 (59.3%) of the examined carcasses were diagnosed as having one or more of these renal lesions. Two hundred and seventy-two (40.7%) of the carcasses were macroscopically judged as having normal kidneys. A selected material of 250 kidneys representative for each group of lesions based on macroscopic examination and 50 normal kidneys were prepared for histological examination. In the group of kidneys with the macroscopic diagnosis interstitial fibrosis (D4), an accompanying histological finding was proliferative glomerular changes with fatty degeneration of the proximal tubules. Cortical infarct-like lesions (D5) were observed in the absence of thrombo-embolic disease and were considered to have developed in association with local arterial alterations similar to polyarteritis nodosa. PMID- 1455927 TI - Influence of medicinal herbs on phagocytosis by bovine neutrophils. AB - Twenty-six herbal preparations made from 24 medicinal herbs, categorized as antipyretics in Chinese materia medica, were tested in vitro to determine their effects upon phagocytosis of 32P-labelled Staphylococcus aureus by neutrophils isolated from bovine blood and milk. The percentage of phagocytosis was determined after incubating (1 hour at 37 degrees C) 1.25 x 10(7) neutrophils, 1 x 10(8) 32P-labelled S. aureus and 10% skimmed milk with herbal solutions. Concentrations of herbal preparations tested were 100%, 10% and 1% (v/v). When compared with PBSS (0.01 M phosphate buffered saline solution) controls, most of the herbs at high concentrations inhibited phagocytosis while at lower concentrations phagocytosis was increased. All 26 herbal preparations significantly increased blood neutrophil activity at their proper concentrations. The most active herbs in promoting blood neutrophil phagocytosis were observed for Herba verbenae, Flos chrysanthemi, Flos lonicerae, Radix sophorae flavescentis, Herba houttuyniae, Radix isatidis, Herba patriniae, Berberini sulfatis at the lowest concentration and for Folium hibisci at the high concentration with the increased percentage of more than 40.0% in comparison with PBSS control. Of the 19 herbal preparations tested with milk neutrophils, 18 herbs greatly increased phagocytosis at suitable concentrations. The most active preparations in stimulating milk neutrophil functions included Folium hibisci, Flos chrysanthemi, Radix bupleuri, Radix stellariae, Herba houttuyniae, Herba senecionis scandentis, Caulis lonicerae and Flos lonicerae which increased phagocytosis by over 35.0%. PMID- 1455928 TI - Electron microscopic studies of bovine progressive degenerative myeloencephalopathy in brown Swiss cattle. AB - Selected peripheral nerves from animals affected with Bovine Progressive Degenerative Myeloencephalopathy (BPDME) were examined by transmission electron microscopy. Changes in axons were both degenerative and reactive in nature and included axonal swelling in conjunction with accumulation of altered organelles and various forms of vesicles. Affected axoplasm was often vacuolated and shrunken, with loss of microtubules and microfilaments and separation of the axoplasmic membrane from the myelin sheath. Segmental disorganization of the normal lamellar pattern of myelin sheaths was observed. Affected myelin sheaths exhibited intramyelinic vacuoles or myelin bubbles often in association with concurrent axonal changes. Schwann cells occasionally contained swellen and vacuolated mitochondria and membrane-bound vesicles. Axonal and myelin changes were considered similar, if not identical, to those described in the central nervous system of affected animals reported in the literature. Collectively, the changes described in the axons and myelin sheaths of the peripheral nerves studied were considered to be compatible with the "dying back" process described in various distal axonopathies. A metabolic defect in the enzyme systems associated with axonal transport was postulated to explain these peripheral nerve lesions. PMID- 1455929 TI - Adenocarcinoma of the ethmoid olfactory mucosa: a histopathological and ultrastructural study with evidence of virus-like particles. AB - A histopathological, morphometric and ultrastructural study was made of enzootic nasal neoplasia in a group of 25 Verata goats. A nasal adenocarcinoma was diagnosed. The neoplasm contained two clearly defined zones, one cystic and the other compact. The tumour stroma was composed of abundant loose connective tissue, in which mononuclear infiltrate was clearly identifiable. The observed viral particles were morphologically similar to Visna-Maedi. These particles had an eccentrically located electrodense core. The diameter of the virus was about 90 nm and it showed envelope numerous spikes on the surface. The virus is assumed to be the causative primary agent of the tumour. PMID- 1455930 TI - Urinary Tamm-Horsfall glycoprotein concentrations in normal and urolithiasis affected male cats determined by an ELISA. AB - A precise and reproducible enzyme-linked immunosorbent assay (ELISA) which measures urinary cat Tamm-Horsfall glycoprotein (cTHP) was developed in order to investigate the possible role of cTHP in the pathogenesis of feline urolithiasis. Reproducible quantification required that the cTHP be disaggregated with 2M urea and 0.05% Tween 20. It was necessary to standardize rigidly the handling of the samples prior to analysis, since the apparent cTHP concentration varied depending on the preanalysis protocols. Using the sample handling protocol of freezing urine at -70 degrees C before dialysis, urinary cTHP was quantified in male cats with no history of urolithiasis ("normal" cats) and in male cats with a history of urolith formation ("urolithiasis" cats). The mean cTHP concentration in adult, male "normal" cats of 49.2 +/- 35.5 micrograms/ml (N = 23) was significantly lower than the mean cTHP concentration of 95.4 +/- 34.1 micrograms/ml (N = 9) in "urolithiasis" cats (p < 0.01, Students' T-test). These findings indicate a correlation between urolithiasis and high urine cTHP concentrations in male cats which warrants further investigation. PMID- 1455931 TI - C-reactive protein--a characteristic feature of health control in swine. AB - In this study 120 weaned female piglets were clinically examined and porcine C reactive protein (CRP) concentration determined in blood serum by means of a competitive enzyme ligand assay. CRP values were put into relation to clinical (catarrh, diarrhoea, inflammation and fever) and pathomorphological findings. It was found, that CRP values are clearly elevated during infections with fever and inflammatory processes, but not in the case of catarrh and diarrhoea. The pathomorphological investigations of some animals with clinical findings revealed changes in lungs, bowels and liver. Special attention has to be paid to the fact that, as in man, CRP is an acute phase reactant, and therefore a sensitive, but non-specific indicator for infections and inflammation processes. Serum CRP screening seems to be a good means for the supervision of the general state of health in pigs. PMID- 1455932 TI - Diurnal changes in cortisol level, neutrophil number and lyzozyme activity in foals during the first 13 weeks of life and in their lactating mothers. AB - In the blood of 11 foals and their lactating mothers (Standardbred) diurnal changes in the cortisol level, neutrophil number and lysozyme activity were studied during the first 13 weeks of life. The investigations began when a foal reached 7 days of age and were repeated every two weeks till 13 weeks of age. Blood samples were taken from the jugular vein every 4 hours for one day. Experiments were repeated in two following years. In the first year 6 mares and 6 foals born by these mares were examined, and in the second year--5 of the mares from the first year and the 5 new foals borne by them. All horses were kept and fed under the same conditions. Diurnal rhythm in neutrophil number and lysozyme activity was found neither in foals nor in mares. In the cortisol level a diurnal rhythm was found as early as in the first week of life of a foal as well as in the first week of lactation in mares. The mean diurnal values of cortisol level and lysozyme activity in foal blood were lower by 58% and 22%, respectively, in comparison with mares. PMID- 1455933 TI - The ultrastructure of cells and cell fragments in mammary secretions of Camelus bactrianus. AB - The fine structure of leucocytes from the udders of 7 lactating and 3 non lactating bactrian camels and from peripheral blood were studied. The most important finding was the presence of large numbers of cell fragments in milk. The cell fragments were bounded by a plasma membrane, had no nuclei and contained mitochondria and abundant rough endoplasmic reticulum (RER). Macrophages were the dominant cells recovered from milk and udder washings during the dry period. Neutrophils and lymphocytes were also present. The dominating leucocytes in blood were neutrophils, followed by lymphocytes, eosinophils, monocytes and basophils. PMID- 1455934 TI - Evaluation of diagnostic tests using relative operating characteristic (ROC) curves and the differential positive rate. An example using the total serum bile acid concentration and the alanine aminotransferase activity in the diagnosis of canine hepatobiliary diseases. AB - The value of a diagnostic test depends on most cases on its ability to discriminate between patients with and without a certain disease. One way of evaluating a diagnostic test is to use the relative operating characteristic curve (ROC curve) and the differential positive rate (DPR). The ROC curve displays the relationship between the true positive ratio and the false positive ratio for a range of cutoff values and it can be used to compare various diagnostic tests under equivalent conditions (equal true positive ratios or false positive ratios) and over the entire range of cutoff values. The DPR is the difference between the true positive ratio and the false positive ratio at various cutoff values and it can be used to obtain the cutoff value associated with the highest sensitivity and specificity. The purpose of this study was to describe the evaluation and comparison of diagnostic tests using ROC curves and DPR. Eventually, the positive and negative predictive values were used to assess the differences between the sensitivity and specificity obtained when the upper limit of the reference interval, or the optimal cutoff value indicated by the DPR, was used as cutoff value. To illustrate the methods, the 2 h post-prandial total serum bile acid concentration (PSBA) and the alanine aminotransferase activity (ALAT) in the diagnosis of primary or secondary hepatobiliary diseases in dogs were used. The ROC curves showed, as expected from previous studies, that PSBA was superior to ALAT in diagnosing dogs with hepatobiliary diseases. Using DPR, the optimal cutoff value for PSBA was suggested to be 15.48 mumol/l. Compared to the traditionally used cutoff value of 22.24 mumol/l, no decisive difference in the positive predictive values were observed. However, the cutoff value of 15.48 mumol/l appeared to produce higher negative predictive values compared to a cutoff value of 22.24 mumol/l. Seemingly, ROC curves and DPR are simple methods useful to the evaluation of diagnostic tests and due to the simplicity, there seems to be a great potential for these methods in the evaluation of diagnostic tests in veterinary medicine. PMID- 1455935 TI - [Comparative studies of diagnostically significant enzymes in plasma, udder lymph and milk of healthy cows and cows with udder diseases]. AB - Different secretions (colostrum, milk, dry udder secretion) of every quarter, peripheral lymph from superficial lymph vessels of the mammary gland and blood from the V. epigastrica superficialis were obtained in 43 cows at different stages of lactation. In these samples the activity of 5 enzymes (LDH, NAG, AP, LAP, GGT) was determined. Levels of LDH and NAG were highest in blood plasma and udder lymph. Levels of LAP, AP and GGT were highest in milk increasing in this order. LDH, NAG, AP and LAP were correlated in both compartments. Changes of the functional state (dry or colostral period) and tissue disturbances of the mammary gland were accompanied by marked changes of enzyme activity in the secretions, but were without obvious influence on enzyme levels in blood plasma and udder lymph. PMID- 1455936 TI - Inhibition of D-galactose transport across the small intestine of rabbit by zinc. AB - Zinc is an essential trace element necessary to life. Many metallo-enzymes involved in the metabolism of carbohydrates, lipids, proteins, and nucleic acids require zinc for their functions. The aim of this study was to characterize how zinc acts on the intestinal sugar absorption in rabbit. Results obtained show that zinc decreases both D-galactose accumulation in the jejunum tissue, and mucosal to serosal transepithelial flux of this sugar, in a dose-dependent way. Furthermore, zinc seems not to modify sugar diffusion across the intestinal epithelium. The inhibition of intestinal sugar transport by zinc seems to be of a competitive type and it is reversed in high proportion with dithioerythritol (thiol groups protector). The results suggest that zinc decreases carrier mediated intestinal sugar absorption. PMID- 1455937 TI - Effect of niacin supplementation on the concentration of niacin in rumen and duodenal digesta and in whole blood of sheep. AB - 1. Niacin concentrations in rumen liquor, duodenal digesta and blood, and daily duodenal flow of niacin were measured in four wethers which were fed an oatstraw grain concentrate diet (with normal niacin content) or an oatstraw maize diet (with low niacin content). The effect of an intraruminal supplementation of 2 mmoles nicotinic acid (NIA) or nicotinamide (NAM) on concentrations of NIA and NAM in gastrointestinal contents and blood and on daily duodenal flow of NIA and NAM was studied. The animals were equipped with rumen fistula and duodenal re entrant cannulae. 2. NIA concentration in strained rumen liquor was 384 and 264 nmol/ml and daily duodenal flow of niacin was 616 and 528 mumoles/d in animals fed normal or low niacin diet, respectively. Intraruminal administrations of 2 mmoles of NIA or NAM raised NIA concentration in strained rumen liquor for approximately 6 h. About 20% of the administered dose of NIA or NAM passed out of the rumen and resulted in a 41% increase in daily duodenal flow of niacin. The remaining 80% of the administered dose of NIA or NAM disappeared from rumen liquor without being washed out. 3. Supplemented NAM was rapidly hydrolyzed to NIA and ammonia when administered into the rumen. 4. NAM concentration in blood appeared to be unaffected by the dietary content of NIA or by niacin supplementation. 5. The NIA concentration in strained rumen liquor was positively related with niacin content of the diet. Increases in duodenal flow of niacin had no marked effect on concentration of NAM in blood. It appeared that feeding diets with different NIA content affected apparent niacin synthesis in the rumen. PMID- 1455938 TI - [B-mode, M-mode and Doppler sonographic findings in mitral valve insufficiency of horses]. AB - B- and M-mode echocardiography was performed on 38 horses. 34 patients had systolic heart murmur with the point of maximal intensity over mitral valve. Additionally, 17 of these patients were examined with the pulsed wave doppler echocardiography (Vingmed 200). In 26 patients with cardiac murmur and in 4 patients without cardiac murmur a mitral valve insufficiency was diagnosed by echocardiography. In 8 horses with a systolic murmur over mitral valve M- and B mode evaluation could not reveal a haemodynamic importance of the murmur. The diagnosis of MVI was based on a dilation of left atrium with or without additional dilation of left ventricle on one hand and with a regurgitation of blood into left atrium found by pulsed wave doppler on the other hand. In 6 extremely dilated hearts a "real" ostium of regurgitation was detected as a direct echocardiographic finding in B-mode. Good correlations existed between echocardiographically evaluated changes of heart dimensions and autopsy measurements in 10 cases. The prognosis seems to be poor if systolic murmurs coincide with dilatation of left atrium and left ventricle, regurgitation of blood into left atrium or with a high degree dilation of left atrium without changes of left ventricle chamber size. In hearts with little to medium dilated left atrium without changes of left ventricle dimension and additionally a regurgitation into left atrium the prognosis seems at least to be cautious. Echocardiography is an available diagnostic help in evaluation of the importance of systolic murmur with the point of maximal intensity over the mitral valve especially in completion by pulsed wave doppler. PMID- 1455939 TI - [The diagnosis of listeria encephalitis in ruminants using cultural and immunohistologic methods. II. Immunohistologic studies in formalin-fixed paraffin sections]. AB - The unlabelled peroxidase-antiperoxidase (PAP)-technique was compared with the avidin-biotin-peroxidase-complex (ABC)-technique in the identification of Listeria antigen in formalin-fixed paraffin sections of 58 ruminant brains, 44 of which showed histopathological lesions typical for listeric encephalitis. Rabbit hyperimmune serum, obtained by immunization with a Listeria monocytogenes strain of serotype 1/2 a, served as primary serum in the immunohistochemical investigations. The antiserum was tested for specificity using formalin-fixed smears of various bacterial species. Listeria antigen was demonstrated in 40 of the 44 brains with histopathological CNS alterations, as seen in listeriosis, using the ABC method, whereas their identification with the PAP method only succeeded in 34 of the brains. Despite the higher dilution of the primary antibody, the ABC method distinguished itself further, in comparison with the PAP method, through more intense immunohistochemical staining of Listeria antigen. Listeria spp, could be isolated from 46 of 52 brains, which were also examined bacteriologically. They could be isolated from 14 brains, which showed no histopathological lesions indicative of listeriosis. In contrast to this, Listeria antigen was only detected immunohistologically in brains with typical histological listeric CNS alterations. In three cases the presumptive histological diagnosis could not be confirmed immunohistologically. PMID- 1455940 TI - Immunohistochemical and ultrastructural investigation of granular cell tumours in dog, cat, and horse. AB - Six canine, one feline and one equine granular cell tumours (GCTs) were investigated electron microscopically and immunohistochemically. The tumours were tested for reactivity with monoclonal antibodies against vimentin and desmin and with polyclonal antibodies against cytokeratin, S-100 protein, glial fibrillary acidic protein (GFAP) and neuron specific enolase (NSE). All GCTs were characterized by their PAS positive cytoplasmic granules in light microscopy, which in electron microscopy appeared as lysosome-like granules. In each case two canine GCTs were stained by the antibody against cytokeratin, vimentin and S-100 protein. Cells of the equine GCT showed reactivity with the antiserum against S 100 protein. In the feline GCT no reactivity with any of the antibodies tested was observed. These differences of the immunohistochemical reactions of GCTs suggest a nonuniform histogenesis of GCTs in domestic animals. The reactivity of the tumour cells with the antiserum against NSE is discussed. PMID- 1455941 TI - Experimental dermatophilosis. AB - The histopathologic features of an experimental dermatophilosis of rabbit skin were described. The strain of Dermatophilus congolensis used for the experimental infection was obtained from the unique isolation and cultivation of this actinomycete from the ulcerous leg lesion of one male patient. Further strains in experiment came from the collections of type cultures. The experimental infection was characterized as an exudative and crustal dermatitis with acanthosis and subcorneal abscesses. Branching hyphae and clusters of coccoid bodies were found mostly in the parakeratotic layer and infrequently in the abscesses. Both the coccoid bodies and the hyphae were Gram-positive. The hyphae were acid-fast but the coccoid bodies were non-acid-fast. The fine structure of hyphae and coccoid bodies, namely of those with flagella, was also described by means of a transmission and scanning electron microscope. PMID- 1455942 TI - Acidification of the colonic mucins following polyvalent colonization of the germ free rat. AB - Colonic mucins of germ-free (GF) and conventional rats (CV) were compared. After isolation by gel filtration on Sepharose CL-4B and purification by density gradient centrifugation, the content of isolated colonic mucins was estimated by determination of PAS positive carbohydrates. Purified mucins were subjected to carbohydrate and amino acid analysis and separated into mucin subclasses by ion exchange chromatography. While the total amount of colonic mucins was not statistically different in GF and CV animals, analysis of carbohydrate composition demonstrated an increased amount of sialic acid in CV rat mucin. This was in accordance with results of ion exchange chromatography, revealing a significant higher amount of negative charged mucin subclasses in CV mucin, compared to the germ-free counterpart. The results of amino acid analysis were similar in both groups. The compositional differences in carbohydrate moieties are attributed to modulations by the intestinal flora. A selective bacterial degradation of the neutral mucin subclasses and modifications in the mucin composition due to a stimulated synthesis are discussed. PMID- 1455943 TI - A direct plating method for monitoring the contamination of Listeria monocytogenes in silage. AB - Twenty-two silage samples were analyzed for the presence of L. monocytogenes using five Listeria selective plating media, with and without previous selective enrichment step. L. monocytogenes was recovered from 3 samples by both procedures, but direct plating allowed the quantification of Listeria population. Two of these positive samples were implicated in outbreaks of listeriosis in sheep; the L. monocytogenes population in these samples was about 10(6) cells/g. The L. monocytogenes population in the other positive sample was 10(3) cells/g. Direct isolation of L. monocytogenes was only possible from LPM, PALCAM and LSAMm media. MOX and LSM media were not selective enough to allow direct Listeria isolation. In our hands, LSAMm was the most suitable plating medium for the direct isolation and specific quantification of L. monocytogenes from silage employing a red blood cells overlay technique. PMID- 1455944 TI - Isolation and characterization of immunoglobulin binding proteins from Staphylococcus intermedius and Staphylococcus hyicus. AB - 125-I-IgG binding activities were observed with 15 (17%) of 90 S. intermedius isolates from dogs and 39 (95%) of 41 S. hyicus isolates from pigs. Binding activities were not detected with S. hyicus isolates from cows. The IgG binding proteins of 2 S. intermedius, 2 S. hyicus, and protein A from S. aureus Cowan I were isolated from their cell surfaces. The proteins precipitated with IgG preparations from human, rabbit, pig, dog and horse, but not with IgG from cow, mouse and chicken. This indicated that these IgG binding proteins could be classified as type I receptors. In addition, the isolated proteins from all 3 staphylococcal species precipitated with polyclonal chicken anti-protein A antiserum. SDS-PAGE, Western blotting and gel isoelectric focussing of the proteins revealed numerous bands in the 42,000 D range and acid isoelectric points. The isoelectric point of the isolated proteins from both S. intermedius cultures was slightly more acidic than those from S. hyicus and S. aureus. The present results indicate a close functional and antigenic similarity, if not identity, between IgG binding proteins of S. intermedius and S. hyicus, and protein A of S. aureus. PMID- 1455945 TI - In vitro antibacterial activity of the lactoperoxidase system towards enterotoxigenic strains of Escherichia coli. AB - The lactoperoxidase-thiocyanate-hydrogen peroxide (LP) system inhibited the growth of enterotoxigenic Escherichia coli strains responsible for scouring in neonatal and post-weaning piglets. An enzymatic system for hydrogen peroxide generation (glucose oxidase, GO; 0.1 U/ml) and a chemical source (sodium carbonate peroxyhydrate, SCP; 90 mg/l) were used in the LP system to test 19 strains in a 6-h growth assay at 37 degrees C. Only three strains were highly sensitive to the LP/GO system, while all exhibited significant growth inhibition with the LP/SCP system. Hydrogen peroxide alone had less effect than the complete system. The bactericidal activity of the LP/GO system towards a previously resistant strain was greatly increased by increasing the level of glucose oxidase in the system by three- or five-fold. PMID- 1455946 TI - [The tenacity of Bordetella bronchiseptica in the air]. AB - The survival time of Bordetella bronchiseptica (phase I and III) has been determined at a temperature of 21 degrees C and 27 degrees C and at a relative humidity of 32%, 58% and 76% in a rotating aerosol chamber. The highest survival time (118.8 min half-life time) has been found at 21 degrees C and 76% relative humidity in B. bronchiseptica (phase I). An increasing temperature (from 21 degrees C to 27 degrees C) causes a lower survival time. The phase I strains react more sensitive to this changing of environment than phase III strains. An increase of relative humidity leads to a higher survival time concerning phase I strains. In contrast phase III strains of B. bronchiseptica react with an increasing survival time. On the basis of the detected half-life time one must suppose an aerogenous distribution of the germ in all stages of animals, especially in intensive husbandry. PMID- 1455947 TI - [The role of calcium in the mechanisms of the cholinergic and glutamatergic signal transduction in the central nervous system (a topical article)]. PMID- 1455948 TI - [The neuronal electrical responses of the superior cervical ganglion in the rabbit to nociceptive skin stimulation]. AB - The patterns of tonic activity in the neurons of rabbit superior cervical ganglion at rest and during noxious stimulation of the skin were studied using intracellular recording. According to reflex changes in the activity patterns, all neurons studied were classified into three groups. Cardiac rhythmicity is more pronounced in the neurons of the second type than in those of the first type. The magnitude of the cardiac rhythmicity in both types of neurons was reduced after noxious stimulation of the skin. In the third type of neurons the cardiac rhythmicity was absent. In some neurons slow excitatory and inhibitory postsynaptic potentials appeared resulting from skin stimulation. PMID- 1455949 TI - [The visual cortex "on command": 2 modes of operation of neuronal mechanisms (a topical article)]. AB - Orientation tuning (TO) of 152 single units in the 17th area of cat cerebral cortex was studied under different contrasts of the light bar flashed in RF (2.3, 10 and 100) and also under local and general anaesthesia (Sombrevin, 4 mg/kg or Nembutal, 35 mg/kg). An invariance of preferred orientation to contrast or anaesthesia was revealed in 40-50% of cells. Noninvariant cells shifted significantly their preferred orientation on 22-90 degrees. Invariant units more often have a simple RF, more sharp OT and preferred horizontal and vertical orientations. Under the low-contrast conditions or under general anaesthesia, noninvariant neurons shifted their preferred diagonal orientations. Different role of the two neuronal groups in detection of the reper (horizontal and vertical) and other orientations in a normal conditions (high-contrast, alert state) in comparison with their behavior under worse conditions (low-contrast, narcosis or sleep) is discussed. PMID- 1455950 TI - [The evolutionary problems of the family of human and animal macroglobulins]. AB - Studies have been made on physicochemical and immunochemical properties of macroglobulins, as well as of associated with pregnancy glycoproteins, from human subjects, mammals, birds, fishes and invertebrates. It was shown that these proteins exhibit similar composition, structure and capacity to bind proteinases inhibiting the latter. Using immunochemical methods, reactions of antigenic identity of these proteins were investigated. A hypothesis of evolutionary formation of macroglobulin family is discussed. PMID- 1455951 TI - [The distribution and properties of the Mg2(+)-ATPase in the membranes of functionally different muscles in the hen]. AB - From striated (m. pectoralis and myocardium) and smooth (myometrium) muscle tissues of hen, by means of differential centrifugation with Ca-oxalate loading, membrane preparations were obtained with high activity of Mg(2+)-ATPase, i.e. a marker enzyme of tubular membranes of T-system of skeletal muscles. Some properties (pH and temperature optima) of this enzyme were investigated and compared to those of Ca(2+)-ATPase from membranes of the sarcoplasmic reticulum. It was shown that in all the investigated muscles, Mg(2+)-ATPase is associated with membrane fraction which in its density corresponds to tubular membranes of T system. Activation of this enzyme is characterized by similar optimal levels of pH (7.2) and temperature (25 degrees C). The activity of Ca(2+)-ATPase in the membranes of the sarcoplasmic reticulum, in contrast to that of Mg(2+)-ATPase, is observed in more narrow bands of pH and temperature, exhibiting tissue specificity. The data obtained, indicating a possibility of chromatographic separation of these enzymes, confirm their biochemical individuality. PMID- 1455952 TI - [The effect of the domestication of Norway rats and silver foxes on the serotonin S1A- and S2-receptors of the brain]. AB - The specific radioligand binding of serotonin 5-HT1A and 5-HT2 receptors was determined in the frontal cortex and in the hypothalamus of Norway rats and silver foxes. Aggressive wild rats and silver foxes and animals selected for many generations for nonaggressive behavior towards man (domestication) were compared. The binding of the 5-HT1A receptors was found to be significantly higher in domesticated Norway rats and lower in domesticated foxes than in aggressive animals. The specific binding of the 5-HT2 receptors was found to be similar in aggressive and domesticated animals, both in rats and foxes. The data obtained indicate the involvement of 5-HT1A receptors in the hypothalamus into the process of domestication. PMID- 1455953 TI - [The hypometabolic effect of the blood plasma from a hibernating suslik Citellus undulatus. Neokyotorphin activates cardiac and respiratory activities in the suslik during arousal from hibernation]. AB - The effect of intraabdominal injection of the blood serum from ground squirrels Citellus undulatus obtained at various stages of the baut has been studied on the level of oxygen consumption in albino mice. The strongest hypometabolic effect exhibited the blood plasma from animals at the beginning of the baut. The onset of baut was used in further experiments on C. undulatus for investigation of activating effects of neokiotorphin (Thr-Ser-Lys-Tyr-Arg) which was earlier found in the brain of the ground squirrel. It was shown that intraabdominal injection of this peptide to hibernating animals facilitates their arousal stimulating both the cardiac activity and respiration. The strongest effect was noted with neokiotorphin of [D-Ser] 2-modification which is more stable to proteolysis. PMID- 1455954 TI - [The hypnogenic effects of delta sleep-inducing peptide (DSIP) analogs: a comparative study in rabbits and rats]. AB - Hypnogenic effects of 3 DSIP analogs with a higher stability against aminopeptidase activity have been studied in rabbits and rats using intraventricular administration (injections and infusions). An analog (D-Ala-2) DSIP augmented slow wave and paradoxical sleep within the 5th, 8th and 11th hours of the recording period. An analog (D-Val-2) DSIP made the same within the 8th and 10th hours, and hexapeptide (D-Ala-2) DSIP (1-6) increased sleep during the 1st, 3rd, and 5th hours. Both nonapeptides augmented sleep in rabbits as well as in rats, though hexapeptide produced this effect in rabbits only, that might be related to some difference in distribution and colocalization of endogenous DSIP like peptide in the pituitary of two rodent species. It may be suggested that hypnogenic activity of DSIP analogs is determined by the structure of administrated molecule, being mediated by such hormones as GRF and CLIP. PMID- 1455955 TI - [The structural-functional characteristics of the rostral sections of the neocortex in Chiroptera]. AB - Studies have been made on the connections of rostral neocortex in bats in order to reveal connections with the structures of the auditory sensory system the existence of which is indicated by evident specific responses to ultrasound in the form of synchronization reaction. It was shown that dorsolateral parts of the rostral neocortex receive topically organized projections from the thalamic nuclei VPL and VL. Connections with the auditory cortex and suprageniculate nucleus are not evident. Afferents of the medial wall of the rostral cortex originate from the thalamic nuclei MD and AM. Possible pathways of auditory afferentation to the dorso-lateral part of rostral neocortex are discussed. PMID- 1455956 TI - [The organization of pulse trains in the dorsal hyperstriatum of hens in relation to the afferent input in ontogeny]. AB - Analysis of background multicellular activity of neuronal populations in the dorsal hyperstriatum of chick embryos and baby-chicks, incubated either in darkness or under periodic illumination, revealed an impulse volley structure which is characterized by onset of discharges which follow each other in a form of small series at close intervals. These series originally may be observed in the background activity of the left dorsal hyperstriatum in "illuminated" chick embryos at the 19th day of incubation, and only at the 1st day after hatching--in the right dorsal hyperstriatum of embryos, "illuminated" although they are present in both left and right dorsal hyperstriatum in embryos incubated in darkness, the difference being presumably due to asymmetric input of visual afferentation to this structure. Series of impulse volleys with repeating intervals are considered as a reflection of the activity of local microsystems of neurons which exhibit cyclic structure and which are capable to maintain stable impulse activity in its intrinsic system of connections, which is one of the elements of a mechanism of synaptic stabilization and formation of organized neuronal complexes. PMID- 1455957 TI - [A neuromorphological analysis of the motor area of the cerebral cortex in rat pups subjected to prenatal exposure to normal and pathological blood serum]. AB - Morphological quantitative and qualitative analysis of the pyramidal neurones in the motor cortex of rat puppies after administration of the blood serum from human donors with central motor disorders reveals the dependence of the quality and quantity of neurones from the effect of corresponding blood sera. Pathologic blood serum decreases the number and induces degradation of dendritic organization of the pyramidal neurones. The effect of the blood sera on quantitative and qualitative properties of the pyramidal neurones in rat puppies depends on the age of donor infants with central motor disorders. Blood serum from newborn babies with motor dysfunctions significantly decreases the number of labeled pyramidal neurones and results in degradation of dendritic organization, whereas sera from 11-13-year infants only insignificantly affect these characteristics. PMID- 1455958 TI - [Species and strain differences in brain structure in rats and mice]. PMID- 1455959 TI - [The prevention of the translocation of intestinal microflora after the rescue of an organism from a terminal state]. AB - In experiments on guinea pigs, the animals were resuscitated from clinical death caused by the acute loss of blood and subsequently treated intragastrically with enterosorbents: activated carbon fibrous material, alone and in combination with polymyxin B, polyphepan (a lignin derivative), polymethyloxan hydrogel and the sorbent Enterocat. In the animals, not treated during the postresuscitation period, a high population level of enterobacteria and Gram-positive aerobic cocci was registered in the contents of the small and large intestines and their translocation to mesenteric lymph nodes, liver, spleen and blood was observed. The amount of lactobacilli in the small intestine was decreased. Enterosorbents were found to decrease a high population level of intestinal microflora, to prevent the translocation of Gram-positive aerobic cocci and to inhibit the penetration of enterobacteria through the enteric barrier in the postresuscitation period. Combined use of activated carbon fibrous material with polymyxin B proved to be most effective for the elimination of enterobacteria. PMID- 1455960 TI - [The structural-functional changes in the cells of Francisella tularensis strain 15 Gaiskii during cultivation and sublimational drying]. AB - Instrumental methods of investigation were used for the demonstration of changes in the fatty acid composition of F. tularensis, strain 15 Gaiskii, during cultivation in solid culture medium, storage after lyophilization, as well as changes in the functioning of the system of membrane-dependent enzymes of the respiratory chain and in the permeability of cell wall membranes by water molecules and NADH after lyophilization. A relationship between the survival rate of F. tularensis cells after lyophilization and stimulation of their endogenic respiration with NADH and succinate was revealed. An increase in residual moisture from 6 to 10-12% was found to intensify the process of lipid peroxidation during the storage of lyophilized F. tularensis cells of strain 15 Gaiskii. PMID- 1455961 TI - [The phenomenon of tachyphylaxis in the pathogenesis of an experimental infectious process]. AB - Experiments on mice have revealed that the development of experimental purulent infection is accompanied by a considerable increase in the nonspecific resistance of the animals to additional infection with unrelated bacteria (the effect of tachyphylaxis). Morphologically, this is manifested by the rapid limitation of the focus of inflammation at the site of inoculation of the superinfecting agent. The state of the phagocytic apparatus is of great importance for this phenomenon as disturbances in the macrophage activity caused by the injection of carrageenan abolish the protective effect of primary infection. The phenomenon of tachyphylaxis has been shown to play a certain role in the prevention of the septic generalization of the process and in resistance to superinfection. PMID- 1455962 TI - [The excretion of Shigella antigens in persons recovering from dysentery]. AB - Shigella antigens can be detected in the excreta of convalescents after dysentery for a long time. Most frequently these antigens occur in feces, less frequently in urine and rarely in saliva. According to indirect data, S. flexneri 1-6 antigens can be detected in excreta for a longer period after convalescence than S. sonnei antigens. When antigen indication is used for the diagnosis of dysentery and epidemiological analysis is carried out, one should bear in mind the length of the agent persistence in the body, related to Shigella type. PMID- 1455963 TI - [The interrelation of the immunity status and intestinal microbiocenosis in young children with acute respiratory organ diseases]. AB - The immune status and the state of intestinal microbiocenosis have been studied in 70 young children with acute respiratory diseases. As revealed in this study, in 85.7% of cases bronchopulmonary diseases are accompanied by disturbances in phasic fluctuations of the immune status and intestinal microbiocenosis. The possibility of repeated acute respiratory infections is predetermined by the intensity of manifestations of immune disturbances and intestinal dysbiocenosis, these two phenomena being directly interrelated. The use of eubiotics jointly with immunostimulants is proposed for the treatment of children with acute bronchopulmonary pathology combined with the unbalance of the immune status and intestinal dysbacteriosis. PMID- 1455964 TI - [The etiological structure of shigellosis in the former USSR--an indicator of the activity of the main routes of infection transmission]. AB - The data on the etiological structure of Shigella infections in the USSR in 1988 1989 are presented. The study showed the dominating role of S. flexneri with S. sonnei also retaining great importance in Shigella infections. The process of the liquidation of S. dysenteriae and S. boydii infections began in some large cities. The domination of dysentery caused by S. flexneri and a high typhoid rate, particularly in Central Asia, were due to poor water supply of the population. The spread of dysentery caused by S. sonnei was completely independent of the water factor. The decisive role in the transmission of S. sonnei in infective doses was explained by decentralized milk supply. PMID- 1455965 TI - [A system for the operative management of hospital infections in maternity hospitals]. AB - A system for controlling the epidemic process of hospital infections in maternity hospitals and departments of infant pathology has been created. The specific feature of the proposed method is the prospective character of epidemiological surveillance: from the cause to the effect, and not vice versa. This is achieved by using the results of follow-up of the preconditions of the epidemic process activation (preterm delivery, gestosis, dry labor, birth injuries in mothers and infants) and the precursors of the beginning aggravation of the epidemic situation (the level of the contamination of infants with hospital microflora). Early information in this respect will help foresee the possible activation of the epidemic process of hospital infections and take necessary measures when infant infection rate is just elevated. PMID- 1455966 TI - [The type subtyping of meningococci by means of whole-cell immunoenzyme analysis]. AB - In this work the method of the whole-cell enzyme immunoassay, used for the serotype-subtyping of meningococci by means of specific monoclonal antibodies, is described. High specificity of the method, the simplicity of the assay procedure and evaluation of its results, as well as the availability of this method for practical use, have been demonstrated. The results of this investigation confirm the importance of the evaluation of type-subtype appurtenance of reference and laboratory strains used in experiments. Study of 72 meningococcal strains obtained from patients has revealed their polyclonal character in respect of their type-subtype signs. PMID- 1455967 TI - [The effect of phospholipids on the adhesive properties of bacteria]. AB - The present work shows that choline-containing phospholipids (lysophosphatidylcholine and lyso-1-alkyl-sn-glycerophosphocholine) inhibit the adhesion of some strains: Bacterium bifidum 1, B. adolescentis MC-42, B. longum B. 379M, Staphylococcus aureus P 209 and Klebsiella pneumoniae 52. Phosphatidylcholine produces no effect on the adhesiveness of these strains, while platelet activation factor stimulates adhesiveness only in strain S. aureus 209. The stimulating or inhibiting action of phospholipids on the adhesive process of microorganisms depends on the species of bacteria and on the concentration of reagents. PMID- 1455968 TI - [The use of immunoenzyme analysis in the diagnosis of candidiasis in patients with different variants of hemoblastosis]. AB - A total of 84 blood sera taken from patients with tumors of the hematopoietic system, among them 63 blood sera from patients with candidiasis and 21 blood sera from patients without symptoms of Candida infection have been tested in the enzyme immunoassay (EIA). This assay has been found suitable for the diagnosis of the visceral forms of candidiasis in patients with acute leukemia and hematosarcoma. EIA has proved to be an inadequate method for the detection of Candida infection in chronic lympholeukemia patients, as well as in patients with acute leukemia and hematosarcoma, suffering from such local forms of candidiasis as candidiasis of the oral cavity. PMID- 1455969 TI - [An increase in the immunogenicity of bacterial antigens under the influence of one of the derivatives of muramyl dipeptide]. AB - As revealed in animal experiments, glucosaminylmuramyl dipeptide (GMDP), the synthetic analog of muramyl dipeptide, when introduced intraperitoneally in a single injection or orally, exhibits adjuvant activity with respect to Citrobacter 0-antigens, Shigella flexneri and enhances the protective properties of dysentery and pertussis vaccines. The stimulating properties of GMDP depend on its dose, the route of its administration, the time elapsed after its administration, its ratio to the concomitant doses of bacterial antigens and to the dose of the virulent culture used for challenge. PMID- 1455970 TI - [The role of tumor necrosis factor and interleukin-1 in forming resistance in experimental Q fever]. AB - Preliminary injections of human recombinant tumor necrosis factor (TNF-alpha) and interleukin 1 (IL-1 beta) increases the resistance of guinea pigs to Coxiella burnetii. The increase of this resistance depends on the dose of cytokines and the time of their inoculation. PMID- 1455971 TI - [The macrophagal-lymphocytic interaction of heterochronic cells in the induction of delayed hypersensitivity]. AB - The influence of senescence on the functional activity of lymphocytes and macrophages in the induction of sensitivity to tuberculosis has been studied in experiments on 226 CBA mice. The study has revealed that after the injection of BCG old animals exhibit decreased capacity for the formation of delayed hypersensitivity, and their lymphocytes, transplanted to recipients, induce a lower level of hypersensitivity. Joint incubation of lymphocytes and macrophages from animals of different ages has shown that immunological defect appearing with age is localized in lymphocytes, while the antigen-presenting function of macrophages remains basically unchanged. PMID- 1455972 TI - [The clinical assessment of the immune status of patients with acute Flexner shigellosis]. AB - A total of 192 patients with Flexner's dysentery 1 have been examined. As a result, sharply pronounced unbalance of cell-mediated and humoral immunity factors has developed in the acute period of dysentery, reaching its maximal manifestations in severe course of the disease. In case of a tendency to a prolonged course of dysentery at the period of convalescence, essential shifts in immunological characteristics persist and the infective agent is repeatedly isolated. PMID- 1455973 TI - [The pathogenesis of intestinal infections and the morphological evaluation of vaccines]. PMID- 1455974 TI - [The role of the intestinal microflora in oxalate metabolism]. PMID- 1455975 TI - [Endemic cholera foci in Asia]. PMID- 1455976 TI - [Superoxide dismutase activity in representatives of the genus Francisella]. AB - Superoxide dismutase (SOD) activity has been registered in representatives of the genus Francisella. The electrophoretic mobility of the enzyme and a number of its isoforms in F. tularensis are linked with the subdivision of this species into several subspecies. Avirulent and noncapsular variants of F. tularensis are characterized by a higher SOD activity than the initial virulent strains. Attempts to detect catalase activity in F. tularensis have failed. PMID- 1455977 TI - [The use of totally decontaminated mice under conditions of complete gnotobiological isolation for obtaining highly adhesive strains of Streptococcus faecium]. PMID- 1455978 TI - Daytime sleepiness: a risk factor in community life. AB - The prevalence of daytime sleepiness and background factors associated with it were investigated in a study carried out at the UKK Institute. The inquiry took the form of a questionnaire mailed to 1600 people of middle age. Daytime sleepiness was found to be associated with disturbed night sleep. Women were more tired than men, but men slept more frequently during the day. Those suffering from tiredness complained of poor health more than other respondents. Traffic accidents and other mishaps attributable to tiredness had occurred in 1.3% of cases, and almost 5% of male respondents had dozed off while driving at least five times in their lives. The findings indicate a need for increased attention to disturbance of sleep and daytime sleepiness in routine health screening. PMID- 1455979 TI - Immunological and gadolinium-DTPA MRI evaluation of relapsing remitting multiple sclerosis. AB - The levels of lymphocytes, blood lymphocytes subsets (CD3+, CD4+, CD8+, DR+, CD25+, CD4+, CD45RA+, CD4+, CD29+ cells) and sIL-2r of 10 patients affected by relapsing-remitting multiple sclerosis were serially studied. The identification of the activity of the disease was made by gadolinium-DTPA (Gd-DTPA) MRI. The immunological determinations and the MRI of the brain and spinal cord were performed every 14th day for a period of three months. No significant difference of the immunological values were found between the presence and the absence of Gd DTPA enhancing areas, except lymphocytes (p < 0.05). These immunological parameters, evaluated in the peripheral blood, are not a marker of disease activity in relapsing-remitting MS patients. PMID- 1455980 TI - Depression in the early phase of MS: influence of functional disability, cognitive impairment and brain abnormalities. AB - This study investigated the relationship between depression, physical disability, cognitive deficit and brain abnormalities on magnetic resonance imaging (MRI) in patients with early MS. Eighteen relapsing-remitting MS patients were evaluated: depression was diagnosed according to DSM-III R and measured by the MMPI depression subscale, physical disability was assessed by using the Kurtzke Expanded Disability Status Scale (EDSS) and cognitive functions by means of an extensive neuropsychological test battery. A neuroradiologist blinded to clinical findings quantified cerebral lesion on MRI. Weighted brain area lesion score were developed according to number and size of cerebral lesions. On the basis of DSM III criteria, six patients were classified as having major depression, seven patients had minor depression and five patients were without depressive symptoms. No significant differences were found among the three groups on both neuropsychological performances and weighted MRI lesion scores. However patients with major depression exhibit greater physical disability than the other MS subgroups. A significant correlation was found between MMPI depression subscale and physical disability. This study suggests that at least in the early phase of MS, depression appears more related to the physical disability than to the severity of pathological brain involvement. PMID- 1455981 TI - Sensory and movement-related cortical potentials in nociceptive and auditory reaction time tasks. AB - The processing of a sensory stimulus leading to a simple motor command was studied with scalp-recorded long latency cortical potentials in humans. Two sensory modalities were tested in their ability to activate descending motor pathways: auditory stimuli and painful cutaneous stimuli produced by a CO2 laser. Subjects were asked to react to stimuli with voluntary index finger movements. The stimulus-related and movement-related cortical potentials were recorded simultaneously with five midline electrodes on the scalp. The auditory reaction time, measured from the stimulus to the onset of electromyogram (EMG), was faster (150 ms) than the laser reaction time (350 ms). The onset of EMG of finger movements occurred only after the first negative components following auditory or laser stimuli but before the positive components. The latency from the auditory negativity to the onset of EMG was about 50 ms and the latency from the laser negativity to the onset of EMG was about 110 ms. This finding indicates that not only the peripheral afferent conduction but also central processing takes longer in a pain-related somatosensory task than in an auditory task. The frontal peak of Motor Potential (fpMP), a cortical potential related to the sensory feedback from movement, occurred with a constant latency after the onset of EMG (100 ms) and was unaffected by the task. PMID- 1455982 TI - Abduction nystagmus in internuclear ophthalmoplegia. AB - Direct current electro-oculography revealed abduction nystagmus with hypermetric abduction saccades in 35 of 64 patients with unilateral and 55 of 66 patients with bilateral internuclear ophthalmoplegia. Slowing of abduction saccades occurred in 27 unilateral cases, mainly ipsilateral to the paretic eye, and in 36 bilateral cases. Abduction nystagmus with hypermetric abduction saccades of normal velocity is explained by an increased phasic innervation adjusted to adduction paresis. Slowed abduction saccades are attributed to impaired inhibition of the medial rectus muscle. Superposition of impaired medial rectus inhibition and increased phasic innervation best explains abduction nystagmus with slowed hypermetric (6 unilateral and 23 bilateral cases) or normometric abduction saccades (9 unilateral and 5 bilateral cases). PMID- 1455983 TI - Treatment of myotonia with antiarrhythmic drugs. AB - The effects of disopyramide, phenytoin, mexiletine, and tocainide were compared in 30 patients with myotonic disorders. The severity of myotonia was assessed by clinical and electromyographic criteria at the end of each treatment phase lasting four weeks. Mexiletine (MXT) and tocainide (TCD) were found to be the most potent antimyotonic agents. The antimyotonic efficacy of MXT and TCD is explained by their fast-blocking effect on voltage-dependent sodium channels in the muscle membrane. The benefits of myotonia control with pharmacological agents must be weight against the risk of therapy in the individual patient. Because of the risks of hematologic problems, TCD is not recommended by us for the treatment of myotonia. PMID- 1455984 TI - Brain energy metabolism studied by 31P-MR spectroscopy in a case of migraine with prolonged aura. AB - The brain and skeletal muscle oxidative metabolism of a patient with prolonged aura was studied by phosphorus magnetic resonance spectroscopy. We found that the phosphocreatine to ATP ratio in brain was reduced, while the inorganic phosphate to phosphocreatine ratio and the calculated ADP concentration were increased. The phosphorylation potential and percentage of maximal rate of ATP synthesis were also altered. Intracellular pH and inorganic phosphate concentration were normal. In muscle we found a low post-exercise recovery of phosphocreatine. These data indicate an impairment of energy oxidative metabolism both in brain and muscle. PMID- 1455985 TI - Screening for unruptured familial intracranial aneurysms. A decision analysis. AB - Decision analysis is used to assess the decision to screen for unruptured intracranial aneurysms (IAs) in two affected families, and to formulate guide lines for similar decisions. Four strategies are compared: "no screening", "screening directly", "screening twice", and "screening later". Intravenous and intra-arterial digital subtraction angiography techniques (iv-DSA, ia-DSA) are considered. Life years lived with and without disability are computed for each strategy. Loss of life expectancy with and without discounting and quality correction is used as an outcome measure. "No screening" is the preferred strategy when population based estimates of the prevalence of IAs are used. Thus, the results of this analysis provide no justification for screening patients without a familial history. But a physician who thinks that the risk of an IA is increased may rightly decide for screening, especially when the patient is aged 40 to 60. Ia-DSA is preferable over iv-DSA. A scenario analysis suggests that screening with magnetic resonance angiography is only slightly better than with ia-DSA, because the complication rate of screening plays a minor role in the analysis. PMID- 1455986 TI - Superior sagittal sinus thrombosis and pulmonary embolism: a syndrome rediscovered. AB - Pulmonary emboli as a fatal complication of superior sagittal sinus thrombosis was once well recognized in the literature but appears to have been forgotten. The sagittal sinus appeared to be the source of pulmonary emboli in previously reported cases. Even in patients with no evidence of systemic thrombosis, but who have sagittal sinus thrombosis, the possibility of dislodging pulmonary emboli should be strongly considered. We report a case of nontraumatic sagittal sinus thrombosis complicated by multiple pulmonary emboli and a fatal saddle embolism, likely originating from the thrombosed sinus. Our review of the literature between 1942 and 1990 yielded 203 cases of intracranial venous thrombosis. The overall mortality rate was 49.3%. In 23 cases (11.3%), the venous sinus thrombosis was associated with pulmonary emboli and in these the overall mortality rate was 95.6%. In the 203 cases in our review, those patients who received anticoagulation therapy also had a statistically significant better outcome. Therefore, the presence of pulmonary emboli in association with sagittal sinus thrombosis mandates a sober assessment of the need of anticoagulation therapy in the absence of obvious contraindication. PMID- 1455987 TI - Western blotting analysis in patients with MS using human brain vessels as antigen. AB - Serum samples from patients suffering from multiple sclerosis, other neurological diseases and normal controls were screened by "western blotting" for antibody directed against proteins of human brain vessels purified from a post mortem brain. A small number of sera contained autoantibodies against some of the proteins of the brain vessels, particularly in patients suffering from MS, epilepsy and migraine. The significance of these results is discussed. PMID- 1455988 TI - Evidence for an altered dopamine beta-hydroxylase activity in migraine and tension-type headache. AB - Sympathetic dysfunction is often present in migraine. It has been suggested that serum dopamine-beta-hydroxylase (D beta H) can be taken as an index of peripheral sympathetic activity. We studied the serum D beta H activity in migraine with and without aura and in tension-type headache patients compared with healthy control subjects. The serum D beta H activity was significantly lower in migraine and tension-type headache patients than in the control group. No significant difference was observed among the three groups of patients studied. These findings suggest that patients with migraine and tension-type headache have a sympathetic hypofunction that may play an important role in the pathogenesis. PMID- 1455989 TI - Intermediate syndrome due to prolonged parathion poisoning. AB - A parathion-poisoned patient with prolonged cholinesterase inhibition due to impaired hepatic metabolism and urinary excretion is reported. An intermediate syndrome characterized by respiratory paresis, weakness in the territory of several motor cranial nerves and of proximal limb and neck flexor muscles, persisted for 3 weeks. During this whole period, cholinesterase remained markedly reduced. Serial EMGs with repetitive nerve stimulation pointed to a combined pre- and postsynaptic disorder of neuromuscular transmission. Electron microscopy of an intercostal muscle biopsy showed focal degeneration at the poorly branched postsynaptic folds, and was considered to be nonspecific. PMID- 1455990 TI - Magnetic resonance imaging findings in lupus ataxia. AB - We present a 47-year-old white woman who had a definitive diagnosis of systemic lupus erythematosus (SLE), and developed cerebellar ataxia of sudden onset. MR imaging showed changes characteristics of cerebellar infarct. Due to the absence of vascular risk factors and to the previous diagnosis of SLE, we postulate that the cerebellar infarct is related to SLE. We are not aware of previous descriptions of the MRI findings in lupus ataxia. PMID- 1455991 TI - Anticonvulsant drug teratogenicity. PMID- 1455992 TI - The scientific basis of treatment of idiopathic thoracic scoliosis. AB - The three-dimensional shape of the scoliotic spine must be understood and in particular the lordotic lateral profile addressed before successful derotation can be achieved. It is important that the thoracic kyphosis be recreated, firstly so that the spine can be untwisted, and secondly to bring the thoracic spine once again behind its axis of rotation thus preventing postoperative buckling with the remainder of growth. Stiffer curves require preliminary anterior multiple discectomy with growth plate excision and reshaping of the apical vertebral bodies. The deformity rapidly collapses into himself and 75% of the total correction occurs spontaneously before the second instrumentation stage. The most rigid curves require that the spinal column be shortened at bone level and Leatherman's two-stage wedge resection is ideal for this purpose. For very young spines posterior fusion is both illogical and harmful and it is essential that the growth of the front of the spine be arrested by multiple discectomy and end plate excision. Posterior instrumental recreation of the thoracic kyphosis without fusion in a "trolley-like" procedure allows continued posterior spinal growth. PMID- 1455993 TI - [What new Cotrel-Dubousset instrumentation is used in the treatment of idiopathic scoliosis]. PMID- 1455994 TI - The Alici spinal system in the surgical treatment of scoliosis. AB - The Alici spinal system is an instrumentation used for correction and fixation of various deformities of the spine. Idiopathic scoliosis is the most important indication. Scoliosis is a complex deformity in the frontal, sagittal and axial planes, and this system provides perfect correction in all three planes. Furthermore, it permits stable fixation and can be used for both anterior and posterior spinal fusions. The indications for the anterior Alici spinal system are: mature thoracolumbar or lumbar curves of more than 40 degrees, progressive immature thoracolumbar or lumbar curves of more than 35 degrees, painful mature lumbar curves, paralytic or congenital lumbar or thoracolumbar curves, and mature lumbar curves of more than 40 degrees in thoracolumbar double curves. The indications for the posterior Alici spinal system are: immature thoracic curves of more than 40 degrees, progressive thoracic or thoracolumbar curves of more than 35 degrees, and paralytic and congenital curves. During the last two years, 92 scoliosis patients underwent spinal fusion with Alici spinal instrumentation. Scoliosis was idiopathic in 58, congenital in 20, paralytic in 12, and 2 cases were caused by neurofibromatosis. Twenty-four of the patients underwent 2-stage anterior and posterior fusions. In the remaining 68 patients only posterior fusion was performed. The mean follow-up was 14 months (range, 6-24 months). Preoperatively, the mean curves of the idiopathic, congenital, and paralytic groups were 54.7 degrees, 57.8 degrees, and 83 degrees, respectively. In the idiopathic group the mean correction was 93% with anterior instrumentation, and 74.4% with posterior instrumentation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455995 TI - Results of CD operation in idiopathic scoliosis. AB - In order to evaluate the use of the CD system in scoliosis and kyphosis surgery we performed a partly retrospective, partly prospective study of our patient group. A total of 38 CD operations was performed in the period November 1986 until February 1991. In this group were 24 patients with idiopathic scoliosis, 4 male and 20 female, average age at operation 18 yrs 10 mo (12 yrs 10 mos-42 yrs 2 mos). In 22 patients follow-up was 6 months or more. In the right thoracic curves (n = 22) the preoperative Cobb angle was 59.5 degrees (48 degrees-90 degrees). The average angle after operation was 25.2 degrees (6 degrees-50 degrees), at 6 months 30.7 degrees and final curve 33.8 degrees (12 degrees-55 degrees) 20.1 months postoperatively (9 mos-48 mos). This is 43.2% correction with a loss of correction in the postoperative period of 14.4%. Left high thoracic curves were stiffer with a correction of only 12.8% in 3 patients at 18.3 months. In 4 patients with double curves a first stage Zielke operation was done before the CD operation. The mean curve of 67.8 degrees (45 degrees-108 degrees) was corrected to 20.5 degrees postoperatively with a final correction of 66.1% in 3 patients at 27 months. Without the preceding Zielke operation the mean curve of 44.5 degrees was corrected to 24 degrees at 6 months in 2 patients (46.1% correction). Derotation was evaluated clinically with the Bunnell method and measurement of gibbus height (14 patients had the derotation maneuver, 2 partial and 6 not).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1455996 TI - Segmental evaluation of the surface and radiological deformity after Cotrel Dubousset (CD) instrumentation for King type II and III. adolescent idiopathic scoliosis (AIS): surgical and etiological implications. AB - In this paper we report the segmental effects of CD in each of the three planes of deformity (frontal, transverse and sagittal) in 35 children with AIS (King types II and III) treated by Cotrel-Dubousset instrumentation. Patients were examined preoperatively and in follow-up at 8 weeks and one year, and 15 patients were also examined at two years. Back shape was appraised segmentally as angle of trunk inclination (ATI) at each of ten levels by ISIS and the Scoliometer. The radiographs were measured nonsegmentally for Cobb angle, apical vertebral rotation and spinal balance, and segmentally for both vertebral rotation and tilt (frontal and sagittal plane), and in the rib cage for rib-vertebra angles (RVAs). PMID- 1455997 TI - [Etiology of pseudarthrosis of the leg with loss of bony substance]. PMID- 1455998 TI - [Pseudarthrosis of the tibia following osteomyelitis in children]. PMID- 1455999 TI - [Medical imaging in tibial pseudarthrosis]. PMID- 1456000 TI - Technetium-99m-diphosphonate, gallium-67 and labeled leukocyte scanning techniques in tibial nonunion. AB - On the technetium-99m bone scan the vast majority of nonunion cases show an intense tracer uptake at the fracture site, as do fractures undergoing normal healing. Therefore static bone scintigraphy usually does not contribute to the diagnosis of nonunion. One of the main causes of delayed fracture healing is infection. Increased blood flow and blood pool as demonstrated during the first and second phases of a 3-phase bone scan are consistent with an inflammatory reaction but are not pathognomonic for infection. A gallium-67 scan is indicative of infection if Ga-67 uptake exceeds Tc-99m uptake on the bone scan. The most specific tracers for infection however are leukocytes labeled with indium-111 or technetium-99m. PMID- 1456001 TI - [Angiography in septic pseudarthrosis]. PMID- 1456002 TI - Deep decortication in nonunion of shaft fractures. AB - For many years we have used the "petal" technique of Jarry and Uhthoff in all cases of delayed union or nonunion of long bones. With a chisel or a gouge, cuts are made in the cortical surface of the bone on both sides of the fracture line, and numerous scales are lifted but remain attached at the base, like the petals of a flower. Depending on the cortical thickness, the petals are 2 to 4 mm thick. The surface area of the bone is increased and the haversian canals under the cortical surface (and the blood vessels) are cut open, exposing numerous areas of well-vascularized and highly osteogenetic tissue on all of the exposed surface of the bone. We were able to retrace 26 cases treated in this way between 1968 and 1988. Different types of fixation were used, depending on type and location of the fracture, but sometimes also because we preferred not to change the fixation that had been applied before the patient was referred to us. All fractures united after one operation, in 3 to 18 months. In one case of nonunion of the ulna, with bone loss by gunshot wound, the fracture united, but a stress fracture through a screw hole occurred distally to the fracture site. It did not unite and reoperation was refused. In most cases we have added autogenous spongiosa only grafts, but we think now that their use is questionable in many instances. This technique is quite similar to the subperiosteal decortication of Judet or the shingling technique as described by Forbes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456003 TI - [Treatment of tibial pseudarthrosis using Robert Judet's method of osteoperiosteal decortication]. PMID- 1456004 TI - The fibula pro tibia procedure in the treatment of nonunion of the tibia. AB - We reserve the fibula pro tibia procedure for infected nonunions or for cases that already have been subjected to one or more other methods of treatment. The fibula pro tibia procedure is a technically simple one-stage procedure. The site of the pseudarthrosis is not exposed; hence there is less risk of recurrent infection. Consolidation was achieved in 75% of our cases. The objective findings are positive: consolidation after an average of one year. Knee mobility is normal in most cases, and ankle mobility is only slightly decreased. In most cases the angular deformities are clinically acceptable. All infections have cleared. PMID- 1456005 TI - Locking graft in the treatment of tibial pseudarthrosis. AB - Despite modern treatments of tibial fractures, we still have nonunions. In case of failure we used a method of treatment which has become less popular over the last decades. A rectangular inlay graft is harvested from the anteromedial tibial surface. The graft, measuring about 12 to 15 cm long, is placed over the nonunion with 2/3 of its length on one side and the remaining third on the other side. The graft is turned 180 degrees and fixed with four lag screws in the original donor site. Postoperatively, we place a nonweight-bearing cast for 3 months. The results are quite satisfactory for both nonunions and difficult multi-operated nonunions. PMID- 1456006 TI - Corrective osteotomy for mal- and nonunion of the tibia using the posterolateral approach. AB - An analysis of the results of 9 patients with a post-traumatic malalignment of the tibia, treated by an osteotomy and immediate bone grafting through a posterolateral approach is presented. Fixation was obtained with an external fixator in 8 cases and with a fibular plate in one case. Union was obtained in all cases after an average of 4.8 months. A significant improvement in the malalignment was obtained, especially in the frontal plane and somewhat less in the sagittal plane. Permanent sequellae due to the procedure were not noted. PMID- 1456007 TI - Vascularized bone transfer for tibial pseudarthrosis. Part I: Vascularized fibula transplantation. A report of 4 cases in the treatment of traumatic bone defects of the tibia. AB - The limited experience of reconstruction of four cases of large tibial defects with free vascularized fibular grafts is presented. Healing occurred in three of the four patients, and one developed a distal pseudarthrosis. One graft fractured twice but healed with a hypertrophic callus. PMID- 1456008 TI - Vascularized bone transfer for tibial pseudarthrosis. Part II: Vascularized bone and muscle transfers. Exclusive free fibular bone graft. AB - The techniques of vascularized transfer of a bone segment, or of revascularization of a conventional bone autograft by a pedicle or a microsurgical muscular flap represent one of the most significant advances made during the last years for the treatment of large bone defects of the tibia with associated skin injury. The authors present their experience with 16 cases, including 5 microsurgical transfers. PMID- 1456009 TI - The etiology and pathogenesis of idiopathic scoliosis. AB - Idiopathic scoliosis is a complex three-dimensional deformity and in the thoracic region the essential lesion lies in the sagittal plane in the form of an area of inappropriate lordosis. The thoracic kyphosis is normally protected from buckling by being behind the axis of spinal column rotation but when the thoracic lordosis develops it brings the apical region anterior to this axis and thus under compression with resultant buckling failure of the spinal column. The condition of idiopathic thoracic scoliosis is the opposite to idiopathic hyperkyphosis (Scheuermann's disease), the latter being rotationally stable and not moving out of the sagittal plane. The two frequently co-exist in the same spine with thoracic hyperkyphosis above an area of lumbar lordo-scoliosis. There is a spectrum of normal lateral profile and flat backs at the one end are in danger of buckling (lordo-scoliosis) while round backs at the other end of the spectrum are in danger of being defined as Scheuermann's disease. There is no requirement for a specific pathological process. Engineers describe only two ways in which a flexible column can fall into mechanically-angular collapse (kyphosis) and column buckling (lordo-scoliosis). A number of factors favour column buckling (Euler's law) and thus the bigger a deformity the more likely it will be to continue progressing and the taller and more slender the column the more likely it will be to fail and this we see in our patients with idiopathic scoliosis. Not only is lordosis the essential lesion but it is also the primary abnormality which can be demonstrated in children before lateral curvature and rotation develop. PMID- 1456010 TI - [The Ilizarov method in the treatment of infected pseudarthrosis of the leg]. PMID- 1456011 TI - Antibiotic penetration into bone in relation to the immediate management of open fractures: a review. AB - Bone is a vascular structure, which is capable of responding to changes in the systemic circulation. Antibiotics carried within the systemic circulation reach the capillaries in bone, and depending on molecular size, pass through the capillary walls to enter the fluid space. Following an open fracture, contamination with pathogenic organisms can occur both at the moment of injury, but also in the hospital, which is a particular problem in grade III fractures in which extensive soft tissue damage can occur in combination with an exposed wound. Antibiotics administered intravenously can be measured in bone by both bioassay and radioactive isotope techniques and are shown to reach bone in effective concentrations. It is apparent that short-course high-dose antibiotic therapy is appropriate for open fractures, and need not be continued as long as the normal fracture-healing process continues. However if infection in bone develops, further surgery is important to remove new dead tissue to allow adequate antibiotic penetration into bone. Thus antibiotics are useful when combined with effective surgical management, but do not on their own offer the only answer to management of the patient. PMID- 1456012 TI - The use of gentamicin-PMMA chains in the treatment of infected tibial nonunion. AB - Local antibiotic therapy with gentamicin-PMMA chains and external fixation permit effective simultaneous therapy of both components of infected tibial pseudarthroses: sequestering osteomyelitis and pseudarthrosis. The local concentrations of gentamicin which can be achieved by implantation of gentamicin PMMA chains are far above the MIC of most common pathogens. This form of local antibiotic therapy is superior to any form of systemic antibiotic therapy. The gentamicin-PMMA chains serve as well as space holders for the bone graft to promote bone consolidation in the absence of infection. The results can be improved by successful management of the soft tissue damage often associated with tibial pseudarthrosis. Pedicled or free muscle graft with microvascular anastomosis is the method of choice. PMID- 1456013 TI - Treatment of bone and soft tissue defects in infected nonunion. AB - In the treatment of infected pseudarthroses the general principles of osteitis treatment are applied. This includes radical excision of pseudarthrotic and infected bone tissue, and of diseased surrounding soft tissue. External fixation devices are the preferred method of stabilization of the bone. Based on the data of a retrospective study of 31 Papineau procedures, 65 local flap transfers, and 46 free flap transfers we found that the Papineau procedure works in minor bone and soft tissue defects. Unstable scar formation is a major disadvantage of this method. Local muscular flaps are indicated in the treatment of soft tissue defects in the proximal and medial portions of the lower leg. A prerequisite for free flap transfers is the availability of trained personnel and suitable technical equipment. The option is limited by the patient's vascular situation. This kind of tissue transfer seems to be superior to other methods. For the substitution of bone defects corticocancellous bone transplantation may be used. A promising alternative method to deal with extensive bone defects is osteogenesis produced by callus distraction. PMID- 1456014 TI - [Infection of leg fractures. Technique and importance of the open spongiosa graft supported by the fibula]. PMID- 1456015 TI - The treatment of reflex sympathetic dystrophy syndrome: current concepts. AB - Reflex sympathetic dystrophy syndrome is the currently accepted term for a disorder that has previously appeared in the literature under a confusing array of designations: causalgia, Sudeck's atrophy, algoneurodystrophy, shoulder-hand syndrome, etc. The disorder, which was first described in 1864, is characterized by pain, swelling, limited range of motion with associated signs of vasomotor instability, trophic skin changes and patchy bone demineralization. It appears as an exaggerated response of an extremity to injury: trauma, infection, phlebitis or numerous other lesions. In 35 per cent of the RSDS patients, no precipitating event can be identified. The rational treatment of these patients should be based on a thorough understanding of its pathogenesis. While the optimal management is still controversial, there is a consensus that the best results will be achieved if treatment is started early and adapted to the clinical stage of the disease. The role of physical therapy is still debatable. Sympathetic interruption, corticosteroids, calcitonin, beta-blocking agents and more recently bi phosphonates have been advocated. Proper management may result in the prevention of crippling sequelae. PMID- 1456016 TI - [Measurement of gibbosity and and recumbent angle as a prognostic factor in juvenile scoliosis]. PMID- 1456017 TI - Advances in osteogenin and related bone morphogenetic proteins in bone induction and repair. AB - Bone matrix is a repository of growth and differentiation factors as demonstrated by the induction of local cartilage and bone formation in rats. The bone inductive activity, termed osteogenin, can be dissociatively extracted, and it was isolated by heparin affinity, hydroxyapatite and molecular sieve chromatography. Osteogenin has been purified to homogeneity from bovine bone matrix and the sequences of several tryptic peptides have been determined. The sequences were similar to portions of the amino acid sequence deduced from the cDNA clone of bone morphogenetic protein-3 (BMP-3). The carboxyl-terminal quarter of osteogenin has sequence identity to the corresponding regions of two related proteins BMP-2A and BMP-2B. The bone inductive proteins are members of the TGF beta superfamily, by virtue of the location of the highly conserved cysteines in their carboxyl-terminal region. Osteogenin and related BMPs initiate cartilage and bone formation in vivo. The study of the mechanism of action of these proteins will add considerable new information on the molecular signals controlling endochondral bone formation. In vitro data indicate that osteogenin stimulates the expression of the osteogenic and chondrogenic phenotypes. Our results demonstrate their profound influence on proteoglycan synthesis and degradation in bovine cartilage explant cultures. High affinity specific binding sites have been identified in both MC3T3 cells and articular chondrocytes. In vivo experiments demonstrate the efficacy of primate osteogenin in restoring large calvarial defects in adult baboons, establishing a primary role for osteogenin in therapeutic initiation and promotion of osteogenesis. PMID- 1456018 TI - Pathogenesis of idiopathic scoliosis. The Nottingham concept. AB - There is no generally accepted scientific theory for the etiology of idiopathic scoliosis. Hence, current treatment is pragmatic and not based on knowledge of causation of the deformity. In Nottingham, we have evaluated data from studies of the hips, pelvis, spine, rib cage and trunk muscles in scoliotic (pre- and post operative) and control patients, cadavers and a mechanical model to formulate a new theory of etiology for idiopathic scoliosis (figs. 18 & 19 of ref. 15). Evidence is summarized for the view that idiopathic scoliosis results, in part, from a developmental abnormality in the central nervous system creating rib vertebra angle asymmetry which leads to a cyclical failure of mechanisms of rotation control in the trunk; these involve rotation-inducing (pelvic) and rotation-defending (discal, ligamentous and costal) mechanisms acting mainly in gait. The mechanical breakdown of rotation occurs in association with a lateral spinal curvature and a lordotic segment to create the initial deformity of idiopathic scoliosis. Then, growth, both abnormal (secondary to vertebral hyper pressures) and normal (linear spinal growth) with gravity adds to the initiating and continuing neuromuscular mechanisms to augment curve progression. This theory views the spine in the wider perspective of function in the trunk, evolution and development, all in relation to bipedalism. The goal of etiological research is ultimately to base a treatment on some knowledge of causation of the deformity. PMID- 1456020 TI - Calculation of 3-D deformity in scoliosis by standard roentgenograms. AB - The standard radiological diagnosis of advanced scoliosis consists of roentgenograms of the total spine in anterior-posterior and lateral views. The deformity of the spine is measured by using the Cobb angle, thus only giving the projected angle of deformity, without showing the true 3-dimensional aspect. The 3-D calculation of the deformity is relevant to diagnosis and therapy of scoliosis. In this paper we define angles according to the Cobb definition, evaluate them trigonometrically and show them in two tables. These angles allow the 3-dimensional deformity in scoliosis to be calculated using the standard roentgenograms in two perpendicular views. This procedure enables us to avoid techniques costly in time and effort in hospital routine, such as stereo radiography, computer-analysis or 3-dimensional reconstruction of CT- and MRI investigations. PMID- 1456019 TI - Magnetic resonance imaging (MRI) of the ankle and hindfoot. AB - While Magnetic Resonance Imaging (MRI) has become a routine diagnostic method to deal with pathology of the knee, little has been published about foot and ankle lesions. This is probably due to the anatomic complexity of bone and ligamentous structures of these small joints, necessitating the use of very thin slices from various orientation planes (orthogonal and oblique planes). A special technique is needed allowing a 3-dimensional (3D) analysis, using inframillimetric slices and more sophisticated equipment than for 2-dimensional (2D) MRI (high fields with good homogeneity, specialized image processors...). An initial potential indication of the method is the precise diagnosis of lateral ligamentous components in severe sprains. MRI may determine if surgical therapy is needed. The ligamentous components are reconstructed along their specific planes thanks to the 3D method. Furthermore, assessment of the ligamentous damage is also possible in chronic ankle instability (elongation, fibrotic appearance...). Thanks to the multiplanar approach, associated lesions of articular cartilage can be revealed in ankle sprains. The high sensitivity of MRI in slight modifications of medullary bone allows the early diagnosis of "occult" fractures (not seen on conventional radiographs), osteonecrosis, osteochondrosis and reflex sympathetic dystrophy syndrome. Finally, MRI easily displays all ankle and foot tendons and fascia and is particularly helpful in depicting partial tears and postoperative complications. PMID- 1456021 TI - [The ISIS optic scanner: its use in the evaluation and control of spinal deviations]. PMID- 1456022 TI - Measurement of body surface topography using an automated imaging system. AB - An automatic computer imaging system for recording body surface topography has been developed on a microcomputer-based image processing system. The computer processes fringe patterns generated on the surface of the trunk and reconstructs the complete 3-dimensional form of the surface. From the topographic reconstruction, clinical parameters of scoliotic deformity such as Angle of Trunk Inclination are calculated at a number of levels from the upper thoracic to the sacral region. These multiple level measurements illustrate the change in deformity over the trunk and correspond to measurements obtained using conventional tactile devices on patients. PMID- 1456023 TI - Plaster casts for the correction of idiopathic scoliosis. AB - The authors report their experience in conservative management of idiopathic scoliosis treated in the last 10 years with the Risser localizer cast method. The conclusion is that this method, alone or in combination with braces, is still a particularly effective therapeutic means in the correction of both angular deviation and rotation, provided that a rigid protocol is followed. PMID- 1456024 TI - Brace treatment in idiopathic scoliosis. AB - A German multicenter study with consequent long-term follow-up of patients with idiopathic scoliosis after Milwaukee brace treatment in one out of seven Orthopaedic Clinics showed that brace weaning at the bone age of Risser 4 is followed by early loss of curve correction. According to Oberthaler et al. patients, who were furnished with a brace as outpatients, are inclined to practice a part-time wearing with different brace free intervals. In a longterm follow-up study of 328 patients with idiopathic scoliosis treated at the North German Scoliosis Center in Cuxhaven 123 compliant patients were examined 4 1/2 years after brace weaning. All were asked to wear their braces 23 hours a day and were weaned only at Risser 4-5 or Risser 5. The control rate was 93%. A gain of correction between 9 and 22% was the result. We analysed the composition of the group of 81 noncompliant patients. As far as we could find out the percentage of really non-compliant patients was only 19% compared with a total of 212 patients, who had finished their brace treatment at least 5 years ago. Eight patients (4%) with prebrace values of over 40 degrees Cobb had to be operated, though they were compliant. Based on these results, strict brace treatment in progressive idiopathic scoliosis is recommended, unless no more physiologic way of treatment is available. PMID- 1456025 TI - The conservative management of Juvenile Idiopathic Scoliosis. AB - Juvenile Idiopathic Scoliosis is not a single diagnostic entity but comprises a number of different types of scoliosis. Although detected in the juvenile years, the study of 56 cases shows that in the majority the onset of the scoliosis can be traced back to infancy. It is proposed that the aim of conservative treatment should be to eradicate the deformity and not be content with preventing progression. The principle of using the child's growth as a corrective force to eradicate the deformity is described. An outline of early treatment by corrective plaster jackets is given. PMID- 1456026 TI - Spinal cord monitoring. State of the art. Results in Harrington and C.D. instrumentation for scoliosis. AB - In scoliosis surgery, it is of paramount importance to obtain extensive correction of the curve without compromising the integrity of the spinal cord. Up to now, the wake-up test has been used for the intra-operative assessment of spinal cord function. Besides the fact that the test only provides a single evaluation, it is also encumbered with some potential hazards related to the anesthetic procedure. An additional problem arises when the technique is applied in psychiatric patients. An alternative approach is the continuous recording of evoked potentials obtained from sensory stimulation. The method permits uninterrupted intra-operative monitoring of the neurological status of the cord. PMID- 1456027 TI - Distortion-product otoacoustic emissions in neonates: normative data. AB - Distortion-product otoacoustic emissions (DPOEs) are otoacoustic emissions evoked by two pure tones and used in order to provide a frequency specific assessment of the mechanical properties of the cochlea. This paper first reports complete input output DPOE functions for audiometric frequencies between 867 Hertz and 8 kHz in a normal neonate population (normative data). DPOE results were analyzed as a function of evoked otoacoustic emission (EOE) properties. Neonates having normal EOEs have large DPOEs. DPOE amplitudes in neonates are larger than in adults. Neonates with atypical EOE frequency spectrum without low frequency components had normal DPOE input-output functions only for high frequencies (above 2 kHz). DPOEs could be useful, in association with EOEs, to precisely evaluate the auditory peripheral function in neonates. PMID- 1456028 TI - Steady-state evoked potentials to amplitude modulated tones in the monkey. AB - A frequency-specific, objective assessment of hearing thresholds is required for use in subjects unable to perform behavioural audiometry. One such method using steady-state evoked potentials (SSEPs) in response to amplitude-modulated tones was evaluated in an experimental animal, the macaque monkey. An amplitude modulation frequency of 165 Hz was found to produce optimum response detection in the anaesthetised animal. Auditory thresholds determined by a computerised automatic response detection system accurately reflected behavioural thresholds previously described in this species. PMID- 1456029 TI - A comparison of speech perception of cochlear implantees using the Spectral Maxima Sound Processor (SMSP) and the MSP (MULTIPEAK) processor. AB - The Spectral Maxima Sound Processor (SMSP) is a portable speech processor which has recently been developed at the University of Melbourne for use with multiple electrode cochlear implants. In this processor, the six largest outputs (maxima) of 16 bandpass filters are used to stimulate the cochlea on a place basis at a constant rate. This speech processing strategy has been compared with the MSP(MULTIPEAK) strategy, in which four electrodes are selected for stimulation in every glottal pulse period. The study was undertaken on four postlinguistically deaf adults. The results show that, for this group of subjects, the performance of the SMSP processor was significantly better than that of the MSP(MULTIPEAK) processor for the recognition of closed-set vowels and consonants, open-set monosyllabic words, and open-set sentences in noise, when using electrical stimulation alone. The SMSP mean scores were: vowels 91.3%, consonants 74.9%, words 57.4%, and sentences in noise 78.7%. The MSP(MULTIPEAK) mean scores were: vowels 76.3%, consonants 59.4%, words 39.9%, and sentences in noise 50.0%. PMID- 1456030 TI - Ultrastructure of cultured marginal cells of the guinea pig cochlea. AB - Explants of stria vascularis and spiral ligament of guinea pig cochlea were kept in primary culture. On the explant, proliferating marginal cells advanced by 15 microns/day, suggesting that in vivo defects of the strial epithelium can be covered by new marginal cells. The marginal cells growing in the cell culture dish had a diameter of 12.8 +/- 0.7 microns and formed an epithelial monolayer. Adjacent cells were connected by desmosomes and tight junctions. The cells were uniformly polarized. The apical membrane had small invaginations and numerous microvillus-like extensions, and the convoluted lateral membrane interdigitated with adjacent cells. The basal infoldings were smaller in cultured cells than in vivo; mitochondria were dispersed in the entire cytoplasm rather than concentrated in basolateral infoldings. The basal membrane infoldings of cultured marginal cells did not interdigitate with underlying fibroblast-like cells. Marginal cells were separated from underlying fibroblast-like cells by a fluid filled space which was sometimes enlarged, leading to the formation of "domes" in the otherwise planar epithelium. PMID- 1456031 TI - Prostaglandin synthesis by the lateral cochlear wall under streptomycin influence. AB - The synthesis of 4 prostaglandins (PGs), PGD2, PGE2, PGF2 alpha and PGI2, detected as 6keto PGF1 alpha in the guinea pig lateral cochlear wall (LW) was investigated under streptomycin treatment. Animals underwent daily injections of the antibiotic at dosages of 20, 100 and 200 mg/kg body weight. Prostaglandins were detected 1, 5 and 10 days after drug administration using radioimmunoassay. Under aminoglycoside administration a general reduction of PG-synthesis was evident, which was highest for PGI2. Already after 5 days of treatment the PGI2 synthesis was decreased down to 50% under the lowest drug dosage. The highest antibiotic dosage induced an abrupt decline of PGI2 synthesis, down to 26%, in animals with the longest duration of treatment. The significant synthesis reduction of PGI2 was followed by PGE2. The reduction of PG-synthesis seems to be influenced rather by duration than dosage of drug administration. The decreased synthesis of PGs under streptomycin treatment is interpreted as an inhibition of cell membrane phospholipids, the phosphoinositides. This assumption becomes plausible since the phospholipids represent endogenous precursors of the PG synthesis. PMID- 1456032 TI - Characteristic ionic composition of endolymph is maintained in cultured inner ear. AB - Inner ear anlagen from mouse were explanted on the 16th gestational day (gd) and cultured for 5 days, i.e. corresponding to the time of birth. By using energy dispersive X-ray technique an elemental composition characteristic for endolymph was found within the membranous labyrinth of the explants. The sodium to potassium ratio in the endolymphatic space of the cultured inner ears corresponded to endolymph of the 16th gd fetus in vivo. There was no difference in the endolymph compartment between the cochlear and vestibular halves of the in vitro specimens. Differences in Na to K ratio between endolymph of the inner ears and the surrounding medium were statistically significant. Thus, endolymph regulating mechanisms are active also under organ culture conditions, although not fully optimal. PMID- 1456033 TI - Experimental interruption of the endolymphatic duct and its effect on the DC potential in the endolymphatic sac. AB - The endolymphatic sac (ES) of the guinea pig was isolated from the remainder of the inner ear by means of surgical interruption of the endolymphatic duct (ED). The DC potential in the ES lumen and the morphology of the ES were studied using glass micro-electrodes and a light microscope at various time intervals after the interruption of ED. The DC potential did not significantly change 1 h postoperatively, compared to findings in the non-operated ear, but a significant decrease of the DC potential was observed after 1, 3 and 7 days postoperatively. A histologically-stainable substance in the ES lumen was enhanced on the operated side. The isolated ES shows a disturbance of mechanism(s) maintaining the DC potential and there is a secretion of a stainable substance into its lumen. PMID- 1456034 TI - Absorption of horseradish peroxidase in the endolymphatic sac: ultrastructural cytochemistry using a new electrophoretic technique. AB - Using a newly developed injection technique, the absorption of horseradish peroxidase (HRP) in the endolymphatic sac (ES) of the guinea pig was examined by light and electron microscopy. HRP (molecular weight: 40,000; molecular diameter: about 5-nm) was directly injected into the lumen of the ES by electrophoresis after the recording of a direct current potential in the ES lumen. Both the macrophages floating in the ES lumen and the epithelial cells in the intermediate portion of the ES absorbed intraluminal HRP. The macrophages internalized the intraluminal HRP at a higher rate than the epithelial cells, suggesting that macrophages play a major role in macromolecular absorption in the ES. It was considered that the macrophages took up intraluminal HRP by phagocytosis, while the epithelial cells of the intermediate portion took it up by pinocytosis. In contrast, the epithelial cells in the proximal portion of the ES absorbed little HRP. No penetration through the junctional complexes between epithelial cells was observed in either the intermediate or the proximal portion at any interval after the injection of HRP. This finding indicates that these junctional complexes are impermeable to intraluminal HRP. PMID- 1456035 TI - Experimental basis for lidocaine therapy in cochlear disorders. AB - In order to further our basic understanding of the effects of lidocaine hydrochloride in the inner ear, cochlear potentials and blood flow (CBF) were assessed after intravenous (i.v.), anterior inferior cerebellar artery (AICA), and local round window (RW) lidocaine administrations in guinea pigs and rats. Lidocaine RW applications produced a dose dependent decrease in compound action potentials (CAP) and cochlear microphonics (CM). The sensitivity changes were more pronounced at high frequencies. These findings suggest that lidocaine has specific pharmacological action in the inner ear other than simple anesthesia of the auditory nerve. The basal turn endocochlear potentials (EP) were not altered by topical lidocaine, implicating altered organ of Corti function following local application of lidocaine. RW applications of lidocaine had no effect on CBF or systemic blood pressure (BP). I.v. infusions caused substantial reductions in BP. In the case of systemic infusions the percent changes in CBF were equal to and accountable by the BP changes. The microinfusions (50 mg/ml, 100 nl/min) through AICA produced a 30%, long lasting increase in CBF. However, neither systemic lidocaine nor AICA infusions had an effect on CAP or CM. These findings indicate that systemically given lidocaine may not cross the blood-cochlear barrier and that the cochlear electrophysiological effects due to lidocaine when given locally are partly mediated by direct influence on cochlear hair cell function; they also suggest that lidocaine-induced interference with active ion transport in the lateral wall or an influence on CBF are not contributing factors. PMID- 1456036 TI - Suboccipital acoustic neuroma surgery: results of decentralized neurosurgical tumor removal in Denmark. AB - From 1979 to 1990, a series of 59 patients with 59 acoustic neuromas were operated on in five departments of neurosurgery by at least five different neurosurgical teams, employing the suboccipital approach. Perioperative mortality rate was 8.5%. Complications including hematoma, ventricular hemorrhage, meningitis, hemiparalysis, abducens nerve paralysis, recurrent nerve paralysis, postoperative wound infection and CSF leak were observed in 21 patients (35.6%). Total tumor removal was not possible in 17 patients (28.8%). Converting the postoperative facial nerve function to House-Brackmann (HB) classification, 34 patients (57.6%) were regarded as HB 6. Reconstruction of the facial nerve was attempted in 19 patients (32.2%). Attempts at hearing preservation were unsuccessful in all patients. Failure to attain better results and the importance of centralized treatment of acoustic neuroma are emphasized. PMID- 1456037 TI - The middle ear as a baroreceptor. AB - Under pressure in the middle ear is thought to be important in the pathogenesis of chronic otitis media with effusion and its sequelae, but the cause of the under pressure and the mechanisms responsible for regulation of the normal middle ear pressure are a matter of debate. Numerous studies have examined the effect of large pressure changes on the ear; however, the ear's sensitivity to smaller pressure changes has received little attention. This study examines the sensitivity of the ear to atmospheric air pressure changes induced in the external ear canal. It is concluded that the normal ear is a very sensitive pressure receptor, and that the sensation is probably registered by stretch receptors in the tympanic membrane. Pathological changes in the tympanic membrane are associated with impaired baroreceptor function. The implications of these findings in the physiology of the ear and the regulation of middle ear pressure are discussed. PMID- 1456038 TI - Expression of sialic acids in the developing murine tubotympanum. AB - Sialoglycoconjugates in the developing murine tubotympanum were characterized using lectin histochemistry with wheat germ agglutinin (WGA), Limax flavus agglutinin (LFA), Sambucus nigra agglutinin (SNA), Maackia amurensis agglutinin (MAA), peanut agglutinin (PNA), and neuraminidase treatment. WGA, LFA, MAA, and neuraminidase-PNA labeled epithelial goblet cells, glandular mucous cells, and cell surfaces of adult and newborn murine tubotympanum. SNA did not label any secretory components. PNA labeled secretory cells and cell surfaces of the fetal tubotympanum without neuraminidase treatment. After birth, these secretory cells and cell surfaces were labeled with PNA only after neuraminidase treatment. These results revealed that: Sialoglycoconjugates are produced from glandular mucous cells and epithelial goblet cells and are present on cell surfaces and within the mucous blanket; their terminal tri-saccharide linkage appears to be the sequence Neu5Ac(alpha 2-3)Gal(beta 1-3)GalNAc; sialic acids appear before birth and gradually increase; terminal galactose residues are masked by sialic acids after birth. PMID- 1456039 TI - A study of the photoelectrical signal from human nasal cilia under several conditions. AB - The movement of normal human nasal cilia was analyzed. Ciliary beat was recorded by means of a phase-contrast microscope equipped with a photodetector. The electrical signal was analyzed as follows: i) a power spectrum was calculated in order to measure ciliary beat frequency (CBF), ii) the beat cycles were averaged and the standard deviation of the waveform was computed to determine signal consistency (SC), and iii) the ratio of the duration of the smooth to that of the steep part of the cycles was measured. This was done under three different conditions: 1) normal or "initial", 2) after induction of "function loss", and 3) after "salbutamol stimulation". At "function loss," the cilia beat slower and with less harmony. CBF decreased from an average of 9.0 Hz in the "initial" condition to 5.8 Hz. SC decreased from an average of 5.7 to 1.9. After "salbutamol stimulation", average CBF was partially restored to 7.7 Hz, while average SC increased to 4.4. These findings indicate that in ciliary function studies, SC, as a measure for ciliary beat harmony, may be introduced alongside CBF as a second valuable parameter. In this study we were not able to identify different phases in the signal that might be used as a third parameter to indicate the effective and the recovery stroke. PMID- 1456040 TI - Nasal peak flow rate records in work related nasal blockage. AB - Eleven patients, who had symptoms of blocking nose in relation to exposure to airway irritants in their work environment, and 11 control subjects recorded nasal and bronchial peak expiratory flow rates (PEFRN and PEFRB) during a working week. In contrast to the control subjects the patients demonstrated a pattern of gradual decrease in PEFRN during the working week with restitution during the subsequent weekend and a different day rhythm in PEFRN during working days from days off. The changes in PEFRB were similar but less pronounced. The results indicate that the symptoms of nasal blockage can be visualized by following the PEFRN during a working week and that the changes in PEFRN may have a relationship to different environmental exposures. PMID- 1456041 TI - Ciliary beat of cultured human respiratory cells studied with differential interference microscope and high speed video system. AB - The ciliary beating of upper respiratory tract cells cultured on cover glasses was studied by using differential interference microscope equipped with high speed video. By culturing the cells on collagen coated cover glasses, objectives with higher magnifications could be used. With this system we could evaluate not only ciliary beat frequency, but also amplitude, wave form, orientation and synchrony of ciliary beating. Also some structural anomalies such as compound cilia and tide cilia bundles could be recognized. Ciliary beat frequency measured from 1,026 ciliated cells was 20.6 +/- 4.7 Hz (mean +/- SD). The orientation of ciliary beat directions was random and the mean standard deviation for measured angles was 73.0 degrees +/- 28.9 degrees (mean SD +/- SD). When the ciliary beat frequency was 20 Hz, the time used for effective phase was 0.022 +/- 0.002 s (mean +/- SD), and 0.028 +/- 0.004 s (mean +/- SD) for the recovery phase of beat. This system is advantageous for studying ciliary function because all parts can be studied simultaneously with higher magnification, and the effects of chemical physical mediators can be studied without disturbing effects of the autonomic nervous system or secretory cells. Also, the same cells could be observed before and after challenge with test medication and thus evaluated more accurately. PMID- 1456042 TI - Danger areas of the posterior rhinobasis. An endoscopic and anatomical-surgical study. AB - In 52 cadaveric half-heads, an endoscopic sphenoethmoidectomy was performed. Then, an anatomical preparation with registration of specific data like bulging of the optic canal, thickness of the bony wall covering the optic nerve and the internal carotid artery was achieved, followed by histological sections in specially selected cases. Thus the two key areas of major surgical hazard in the posterior rhinobasis could be clearly demonstrated: the immediate topographic relation of the optic canal and the internal carotid artery to the lateral wall of the sphenoid sinus and the cells of the posterior ethmoid respectively. Onodi cells of varying degrees were found in 42% of all cases. The thickness of bony wall over the maximum bulging of the optic canal averaged 0.28 mm. Bony dehiscences could be demonstrated in 12% of the cases. The technique of data acquisition, the anatomical and histological findings as well as their clinical and surgical relevance are discussed. PMID- 1456043 TI - Developmental changes in expression of a calcium-binding protein (spot 35 calbindin) in the Nervus terminalis and the vomeronasal and olfactory receptor cells. AB - The detailed localization of spot 35-calbindin and its ontogenic change were studied in Nervus terminalis, the vomeronasal organ and the olfactory epithelium of the rat by immunohistochemistry. At the embryonic days 12 and 13 (E 12-13), calbindin-immunoreactive cells were found in the outermost layer of the presumptive olfactory bulb and within the olfactory placode. At E 14 to the postnatal day 1 (P 1), intense calbindin-immunoreactivity was localized in ganglionated fiber bundles of Nervus terminalis coursing through the mesenchymal spaces on both sides of the nasal septum. Nervus terminalis decreased the immunoreactivity abruptly after P 1 and it showed no distinct immunoreactivity for calbindin at P 7 and thereafter. On the other hand, numerous receptor cells in the olfactory epithelium and the thicker vomeronasal epithelium exhibited weak to moderate immunoreactivity for calbindin at E 18-P 1. Their immunoreactivity decreased in intensity progressively after P 7 and no distinct immunoreactivity for calbindin was detected in most of the receptor cells, whereas moderate immunoreactivity was detected in most of the vomeronasal and olfactory nerves at P 28 and P 63. PMID- 1456044 TI - Neuropeptide Y in the rabbit maxillary sinus modulates cholinergic acceleration of mucociliary activity. AB - The distribution of neuropeptide Y (NPY)-immunoreactivity was investigated in the rabbit maxillary sinus and adjacent ganglia. A moderate supply of NPY-containing nerve fibers occurred around seromucous glands and a denser supply around small blood vessels. Only a few immunoreactive nerve fibers were seen beneath the epithelium. Double immunostaining showed that vasoactive intestinal peptide (VIP) coexisted with NPY in the nerve fibers surrounding blood vessels and seromucous glands. NPY-containing nerve cell bodies were numerous in the superior cervical ganglion, and moderately numerous in the sphenopalatine ganglion. The finding of NPY-containing neurons in the latter parasympathetic ganglion suggests that NPY may influence the cholinergic regulation of mucociliary activity. The effect of NPY on the mucociliary activity of the maxillary sinus in connection with cholinergic stimulation has therefore been investigated in vivo using a photoelectric technique. At dosages of 2.5 and 5.0 micrograms/kg, the ganglionic stimulant nicotine bitartrate, which increases mucociliary activity by a cholinergic pathway, accelerated mucociliary activity by 28.0 +/- 7.5% and 36.8 +/- 6.2%, respectively. In the same experiment repeated during infusion of NPY (0.1 microgram/kg/min), the increase in mucociliary activity was reduced to 10.8 +/- 2.3% and 28.9 +/- 7.1%, respectively. Infusion of NPY did not affect the stimulating effect on mucociliary activity by bolus injections (0.1 and 0.5 microgram/kg) of the cholinergic agonist, methacholine. It is concluded that NPY like immunoreactivity is present in nerve fibers in the rabbit maxillary sinus and in neurons in the sympathetic and parasympathetic ganglia that supply the nose and paranasal sinuses. NPY attenuates the effect of nicotine on mucociliary activity, probably via a prejunctional mechanism, and may act as a modulator of cholinergic regulation of the mucociliary system. PMID- 1456045 TI - Retention fluids of chronic sinusitis induce neutrophil adherence to microvascular endothelial cells. AB - The adherence of circulating leukocytes to the vascular endothelium is a critical step in the emigration of leukocytes through blood vessel walls to inflammatory lesions. The influence of nasal secretions on the adherence of neutrophils to the vascular endothelium was investigated using monolayers of human mucosal microvascular endothelial cells derived from the inferior turbinate. Preincubation of vascular endothelial cells with retention fluids from the maxillary sinus of the patients with chronic sinusitis showed increased neutrophil adherence. Recombinant IL-1 beta was also tested and found to induce adherence of neutrophils to human mucosal microvascular endothelial cells. However, no adhesive effect was observed with the nasal secretions of nasal allergy. An enzyme-linked immunosorbent assay detected considerable amounts of IL 1 beta in the chronic sinusitis retention fluids, while the amounts of IL-1 alpha and TNF-alpha were very low. The increased adhesion of the neutrophils by the retention fluids of chronic sinusitis was also neutralized by the incubation with anti-IL-1 beta antibody in a dose dependent manner. These findings suggest that IL-1 beta in the paranasal secretion of chronic sinusitis induces the adherence of neutrophils to vascular endothelium and subsequent infiltration of neutrophils in the paranasal sinuses, thus contributing to the persistence of chronic sinusitis. PMID- 1456046 TI - Expression of epithelial membrane antigen and secretory component in carcinomas of the laryngeal ventricle, epiglottis and vocal cord. AB - Expression of epithelial membrane antigen (EMA) and secretory component (SC) in 11 laryngeal carcinomas from the laryngeal ventricle was studied immunohistochemically and the results were compared with findings in carcinomas originating from the epiglottis and vocal cord. EMA was almost constantly present in laryngeal carcinomas of each type, while the expression of SC was observed in 7 of 11 (64%) ventricle carcinomas, 9 of 34 (26%) carcinomas from the epiglottis and 2 of 11 (18%) carcinomas from the vocal cord. In 4 ventricle carcinomas, immunostaining for SC was intense. It would appear that some carcinomas in the laryngeal ventricle originate from cells of the secretory glandular acini or the epithelium. PMID- 1456047 TI - Serum concentration fluctuation and bioavailability comparison between indomethacin sustained-release and conventional capsules during steady state. AB - The comparison between indomethacin conventional capsule (CC) po 25 mg q 8 h or 25 mg tid and indomethacin sustained-release capsule (SRC) po 25 mg bid in human by crossover design showed that both maximal serum concentration (Cmax) and fluctuation index (FI%) of SRC were significantly lower than those of CC during steady state (P < 0.01). No practical differences were observed between the 2 preparations in the trough serum concentration (Cmin) and area under serum concentration-time profiles (AUC0-tau) (P > 0.05). The time period reaching maximal serum concentration (Tmax) of SRC was much more delayed than that of CC (P < 0.01). It suggested that SRC possesses a better controlled release property and could avoid a higher serum peak concentration of CC. PMID- 1456048 TI - Effects of ohmefentanyl on CA1 field potentials in rat hippocampus slices. AB - The effects of ohmefentanyl (OMF), a new opiate agonist with high affinity and high specificity for mu receptors, was examined on CA1 field potentials in the transverse hippocampal slices. OMF showed two effects upon the evoked population spikes (PS) recorded in stratum pyramidale: 1) a concentration-dependent increase in the amplitude of PS, which was largely reversed by naloxone, and 2) production of a naloxone-reversible additional PS at high stimulus intensities. No significant change was seen in field excitatory postsynaptic potential (EPSP) recorded simultaneously in stratum radiatum. The EC50 for OMF and morphine were 6.6 and 3700 nmol.L-1, respectively. Thus OMF was 560 times more potent than morphine. The mechanism of augmentation by OMF of PS could be attributed to disinhibition as judged from the paired-pulse paradigm. PMID- 1456049 TI - Effects of l-stepholidine on synaptosomal Ca(2+)-ATPase and subcellular calmodulin in rat striatum. AB - Our results showed that l-stepholidine (l-SPD) inhibited basal Ca(2+)-ATPase activity in rat striatal synaptosomes with an IC50 of 31.5 mumol.L-1, suggesting its interaction with Ca2+ transport. l-SPD inhibited also calmodulin (CaM) activated basal Ca(2+)-ATPase in a concentration-dependent manner. A complete reversal of CaM activation of Ca(2+)-ATPase was observed with l-SPD 10 mumol.L-1. The activity of synaptosomal Ca(2+)-ATPase and membrane-bound CaM level were decreased in haloperidol (1 mg.kg-1.d-1, ip) and l-SPD (5, 10, and 30 mg.kg-1.d 1, ip) treated rats for 7 and 14 d, respectively. But the activity of Ca(2+) ATPase and membrane CaM level were increased after treatment with the same of doses haloperidol and l-SPD for 21 d. During the treatments with haloperidol and l-SPD cytosolic and nuclear CaM levels were not altered. These results suggest that l-SPD may modulate the release and synthesis of dopamine (DA) and the negative feedback regulation of presynaptic DA receptors by altering Ca2+ and CaM regulating processes in the central dopaminergic nervous system. PMID- 1456050 TI - Vascular permeability increased by histamine aerosol, capsaicin, and electric stimulation of vagus nerves in guinea pigs. AB - The present study was to clarify the tissue differences in vascular permeability enhanced by 0.1% histamine aerosol, capsaicin (50 micrograms.kg-1, iv), and electric stimulation of vagus nerves (ESV, 12 V, 5 ms, 16 Hz, for 90 s) in different parts of airways, heart, esophagus, ileum, kidney, and liver of guinea pigs using Evans blue (30 mg.kg-1, iv) as a tracer. All the treatments significantly increased the dye extravasation in trachea, main bronchi, proximal and distal intrapulmonary airways (by 64-722%), as well as in the heart (by 89 126%), most remarkable for capsaicin on trachea and main bronchi. Capsaicin also markedly increased the dye content in esophagus. These results demonstrate that neurogenic inflammation induced by capsaicin and ESV primarily increases vascular permeability in the respiratory tract and heart. PMID- 1456051 TI - Effect of dizocilpine maleate on cerebral anoxia and ischemic damage in rodents. AB - The Protective effects of dizocilpine maleate (DM) against anoxia in mice and ischemic damage in rats of 4-vessel occlusion (4-VO) were studied. DM 0.5 or 1.0 mg.kg-1 ip significantly prolonged the survival time of mice in closed containers. DM 0.5 and 1.0 mg.kg-1 ip 30 min prior to 4-VO obviously accelerated the electroencephalographic recovery, reduced the neuronal loss in the hippocampus, and increased the survival rate after 72-h reperfusion. These effects followed a dose-dependent manner. Our results indicate that selective non competitive N-methyl-D-aspartate receptor blocker DM protects against anoxic and ischemic cerebral damage. PMID- 1456052 TI - Effect of intracerebral injection of pirenzepine on electroencephalography and convulsions in conscious rabbits. AB - Intracerebroventricular (icv) injection of pirenzepine (Pir) 2 mg.kg-1 caused EEG spike discharges, which first appeared in amygdala or hippocampus and then in midbrain reticular formation and cortex. After that rabbits developed clonic convulsions. Injection (300 micrograms) into amygdala or hippocampus also produced EEG spike discharges Hemicholinium 3 (HC-3) 50-150 micrograms.kg-1 icv inhibited the EEG spike and seizure discharges in varying degrees produced by Pir. It is suggested that Pir has a central stimulatory action which is related to cholinergic mechanism. PMID- 1456053 TI - Circadian effects of scopolamine on memory, exploratory behavior, and muscarinic receptors in mouse brain. AB - Mice were maintained at light-dark cycle with lights on from 05:00-19:00 for 10 d in laboratory. The study was performed at 07:00-09:00, 15:00-17:00, and 21:00 23:00 in June and July. Scopolamine (Scop, 0.1 and 0.4 mg.kg-1, ip) was injected 15 min prior to training or the first exploratory test. The amnesic effects of Scop showed hyperresponses at 07:00-09:00 and 15:00-17:00, and hyporesponses at 21:00-23:00 using step-through and step-down tasks. The circadian effects of Scop on exploratory behavior were consistent with the findings above mentioned. The numbers of [3H]quinuclidinyl benzilate ([3H]QNB) binding sites in the temporal cortex and hippocampus were more at 08:00 and 16:00 than those at 22:00. However, muscarinic receptor levels in the striatum were lower at 08:00 than those at 22:00. These results indicated that the effects of Scop on memory, behavior in a novel environment, and muscarinic receptors in brain regions showed circadian changes in mice. PMID- 1456054 TI - Global depletion of myocardial norepinephrine and ATP after left coronary artery occlusion in rats. AB - After ligation of the left coronary artery in rats, myocardial norepinephrine (NE) and ATP depletions in both infarcted (IZ) and non-infarcted zone (NIZ) were studied. In IZ, the depletions of NE and ATP were biphasic and the depleting rate constants were found to be K1 = 0.71 h-1 and K2 = 0.015 h-1 for NE, and K1' = 0.52 h-1 and K2' = 0.016 h-1 for ATP. In NIZ, the depletion of NE was monophasic, slowly progressive, and quite durable with rate constant K3 = 0.018 h-1. The depletion of ATP was transient. Propranolol (Pro) and verapamil (Ver) were beneficial but only partly effective against NE and ATP depletions. PMID- 1456055 TI - Electrophysiological effects of cimetidine on rabbit myocardium. AB - Effects of cimetidine (Cim) were studied electrophysiologically on fast action potential (AP) in rabbit papillary muscle and slow AP in pacemaker cell of rabbit sinoatrial node (SAN) as well as on atrioventricular (A-V) conduction in anesthetized rabbit. Cim (0.01, 0.1, 1, and 2 mmol.L-1) induced prolongations of AP duration (APD) and effective refractory period (ERP), slowing down of the maximal rate of rise of phase 0 (Vmax) and of the slope of phase 4 depolarization (SP4), and a decrease of AP amplitude (APA) in concentration-dependent manners. Cim (100 mg.kg-1 iv) prolonged the A-V conduction. The results suggest that Cim, like quinidine, shows a membrane stabilizing effect, which may be the electrophysiological basis of the anti-arrhythmic effect of Cim. PMID- 1456056 TI - Effects of m-nisoldipine on transmembrane currents of guinea pig papillary muscles. AB - Effects of m-Nis on the transmembrane currents were studied using single sucrose gap voltage clamp technique. The amplitude of slow inward current (I(si)) was 10.6 +/- 4.1 microA. Maximal inward current was induced at a membrane potential range between -20 to -25 mV. The amplitude of I(si) were significantly decreased by m-Nis (0.2 mumol.L-1) with a reduction of 47.3%. The transient inward current (I(ti)) induced by ouabain was also greatly depressed or prevented by m-Nis, resulting in the inhibition of DAD. PMID- 1456057 TI - [Evaluation of the tissue-to-blood partition coefficient R for physiological pharmacokinetic models]. AB - The tissue-to-blood partition coefficient R, fraction of drug unbound in blood fB and intrinsic clearance of elimination organ/tissue Cl'L are important parameters used in physiological pharmacokinetic models. Simple equations to evaluate R by AUC were derived in this paper for single bolus iv, the tissue-to-blood partition coefficient of nonelimination organ/tissue was exactly the ratio of AUC between tissue and blood, those equations were examined by the experimental data of rats following iv ethoxybenzamide 20 mg.kg-1, and compared with other methods. Equations to evaluate fBCl'L and other parameters were also given for linear elimination model. PMID- 1456058 TI - [Muscarinic receptor subtypes in respiratory center and their functions]. AB - Radioreceptor binding assays using [3H]quinuclidinyl benzilate and [3H]pirenzepine were performed on the pons and medulla oblongata (MeOb) of rat brain. The M1 cholinergic receptor (M1-R) was found to account for approximately 30-40% of the total muscarinic receptors (M-R) in the pons and MeOb, and the M2 accounted for about 60-70%. The receptor binding capacities of scopolamine and atropine were compared with those of pirenzepine (Pir) and AF-DX 116 on the 2 parts of the brain. The affinity values (pKi) suggest that the selectivity of scopolamine for M1-R is greater than for M2-R, and that of atropine for M2 is greater than for M1. In conscious rabbits, the respiratory frequency (FR), tidal volume (TV), and minute ventilation volume (MVV) were determined. Arterial blood samples were taken intermittently and analyzed for pO2, pCO2, and pH. When pilocarpine (a M1-R subtype selective agonist) was given, excitatory effects on respiration were seen through FR, TV, MVV, and the pO2, pCO2, and pH. When 6 beta acetoxy nortropane (6 beta-AN, a novel M2-R subtype selective agonist) was given, the effects were inhibitory. These results were reversed after administration of Pir, scopolamine, AF-DX 116, and atropine. Thus, it shows that Pir and scopolamine inhibit respiration by blocking the M1-R subtype of the respiratory center, while the excitatory effects of AF-DX 116 and atropine are brought about by blocking the M2-R subtype of the respiratory center. PMID- 1456059 TI - [Effect of mexiletine on energy metabolism of ischemic brain in mice]. AB - After 30 s ischemia induced by decapitation, the contents of ATP and phosphocreatine (PC) in mouse brain reduced, while that of lactic acid (LA) increased. When mexiletine (3.1-50 mg.kg-1) was injected ip 30 min before decapitation, the brain ATP and PC reduction, and LA accumulation were both alleviated in a dose-dependent manner. These findings suggested that mexiletine was effective in ameliorating the energy exhaustion in the ischemic brain. PMID- 1456060 TI - [Effects of 3 henbane drugs on acute forebrain ischemia and reperfusion injury in rats]. AB - After 30-min ischemia and 60-min reperfusions in rats by ligating bilateral vertebral and common carotid arteries, the brain calcium contents were increased from 171 +/- 6 micrograms in control group to 192 +/- 10 micrograms with abnormal EEG activities and ischemic injury in the brain tissues. Anisodamine 6.67 mg.kg 1, scopolamine 0.67 mg.kg-1 or atropine 0.67 mg.kg-1 injected ip decreased the elevated calcium contents of the rat brain to the level of control, reduced the ischemic injury of brain tissue, and promoted the recovery of EEG activities. The findings showed that the 3 henbane drugs might prevent the brain tissues from ischemic damage through reducing intracellular Ca2+ accumulation resulted from ischemia and reperfusion event. PMID- 1456061 TI - [Inhibitory effects of neferine and tetrandrine on portal vein and papillary muscle in rats]. AB - To determine the vascular selectivity, the inhibitory effects of verapamil (Ver), neferine (Nef), and tetrandrine (Tet) on the spontaneous contractile force of portal vein and contractile force of the paced papillary muscle of left ventricle were studied in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The vascular selectivity was expressed by the IC50 ratio (IC50 for papillary muscle/IC50 for portal vein). The results showed that the vascular selectivity values of Ver, Nef, and Tet were 1.15, 0.32, and 0.20, respectively in WKY and 0.80, 0.24, and 0.10, respectively in SHR. It is concluded that Nef and Tet, in contrast with Ver which is devoid of selectivity for either tissue, are more liable to inhibit the myocardium than the vascular smooth muscle. In addition, the IC50 value of Tet for inhibition of the portal vein in SHR was nearly 10-fold higher than that in WKY (237 and 27 mumol.L-1, respectively). This indicates that the response of portal vein to Tet is decreased in SHR. PMID- 1456062 TI - [Role of catecholamines in action of nicotine on slow action potentials in guinea pig papillary muscles]. AB - The action potential duration (APD) of histamine-induced slow action potentials (SAP) and force of contraction (FC) were potentiated by nicotine (0.6-1.0 mmol.L 1) on guinea pig papillary muscles in a concentration-dependent manner. In the presence of atropine, nicotine concentration dependently suppressed the action potential amplitude (APA), APD, the maximal upstroke velocity (Vmax), and FC in catecholamine-depleted (reserpine 2.5 mg.kg-1 ip, 15 h prior to the experiment) muscles. Nicotine (0.6 mmol.L-1) itself induced SAP and enhanced FC. These 2 effects were antagonized by verapamil. A linear relationship existed between APA of nicotine-induced SAP and 1g [Ca2+]0 with a slope of 23.2 mV for a 10-fold change in [Ca2+]0. These results suggested that the effects of nicotine on enhancing Isi were mediated by the release of catecholamines in myocardium. PMID- 1456063 TI - [Effects of propafenone, quinidine, and their combination on ventricular fibrillation threshold in dogs]. AB - The effects of propafenone (Pro), a new Ic anti-arrhythmic agent (AAA), quinidine (Qui), and their combination on ventricular fibrillation threshold (VFT) and other electrophysiological properties were evaluated in 20 dogs. VFT was determined by a train of pulses, 4 ms in duration, delivered at 10 ms intervals. The results showed that in normal anesthetized, open-chest dogs: (1) Pro decreased VFT by 21.4%; (2) Qui increased VFT by 75.5%; (3) the Pro-induced decreased VFT was abolished by simultaneous administration of Qui; and (4) the above effects of the two drugs used separately or in combination on VFT were not related to their effects on ventricular effective refractory period and atrioventricular conduction time. PMID- 1456064 TI - [Effects of ketotifen on human neutrophil respiratory burst and intracellular free calcium]. AB - The stimulatory effect of FMLP 5 nmol.L-1, OAG 25 nmol.L-1 and calcimycin 10 nmol.L-1 on luminol-dependent chemiluminescence (CL) was observed in human neutrophils (Neu). The rest level of Neu intracellular free calcium ([Ca]i) measured by Ca(2+)-sensitive probe Quin 2/AM was calculated to be 200 +/- s 19 nmol.L-1. By the addition of FMLP 0.1 nmol.L-1 or calcimycin 0.5 nmol.L-1, the peak [Ca]i increased to 769 +/- 104 nmol.L-1 and 953 +/- 53 nmol.L-1, respectively. Ketotifen (50-300 mumol.L-1) inhibited Neu CL in a dose-dependent manner with activator FMLP. Inhibition was also seen when Neu CL was activated by calcimycin and OAG, respectively. However, ketotifen did not inhibit Neu [Ca]i increment activated by FMLP and calcimycin. PMID- 1456065 TI - [Therapeutic effects of epimeric glycyrrhizic acids on hepatic injury in rats]. AB - The effects of the epimeric glycyrrhizic acids (GA), 18 alpha-form and 18 beta form, on D-galactosamine (Gal)-induced acute liver injury and fulminating hepatic failure (FHF) in rats were studied. In rats of acute liver injury, extensive liver parenchymal cell damage was observed by the elevation of alanine aminotransferase (ALT) activity and confirmed by significant histopathological changes 24 and 48 h after ip Gal 450 mg.kg-1. Moreover, marked elevation in the liver putrescine levels occurred along with that of serum ALT. The spermidine and spermine levels did not alter significantly. GA 18 alpha-form 300 mg.kg-1 ip suppressed the elevation of serum ALT and liver putrescine levels, and improved all the histopathologic features. On the other hand, GA 18 beta-form 300 mg.kg-1, which exhibited inhibitory effects 24 h after ip Gal, showed no action 48 h after ip Gal. The ALT levels in the serum from GA 18 alpha-form, 18 beta-form, vs control groups after 24 h were 70 +/- 24 (P < 0.01) and 78 +/- 42 (P < 0.01) vs 155 +/- 57, and after 48 h were 74 +/- 25 (P < 0.01) and 258 +/- 99 (P > 0.05) vs 293 +/- 110. The putrescine contents (nmol.g-1) in the liver from GA 18 alpha form, 18 beta-form, vs control after 24 h were 34 +/- 9 (P < 0.01) and 51 +/- 12 (P < 0.01) vs 139 +/- 29, and after 48 h were 16 +/- 3 (P < 0.01) and 150 +/- 11 (P > 0.05) vs 156 +/- 23.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456066 TI - [Pharmacokinetics of gentamicin after intratracheal administration in tracheotomy patients]. AB - Seventeen tracheotomy patients were given gentamicin (Gen) into trachea at the dosage of 2 and 4 mg.kg-1. Gen concentration in serum was determined by fluorescence polarization immunoassay. Pharmacokinetic parameters were calculated by micro-computer pharmacokinetic program (MCPKP). T1/2Ka, Tp, and Cmax were 0.6 +/- 0.3 h, 1.7 +/- 0.7 h, and 4.6 +/- 1.8 micrograms.ml-1, respectively in 4 mg.kg-1 group and 0.3 +/- 0.3 h, 0.9 +/- 0.5 h, and 0.4 +/- 0.2 microgram.ml-1, respectively in 2 mg.kg-1 group (P < 0.05). T1/2Kel was 30 +/- 11 h in patients of serum creatine (Cr) > 2 mg% and 6 +/- 5 h in patients of Cr < 2 mg% (P < 0.01). No significant difference could be found between Cmax of different renal function patients (P > 0.05). PMID- 1456067 TI - [Absorption of ceftizoxime from peritoneal dialysate and its pharmacokinetics in chronic kidney failure patients]. AB - The pharmacokinetics of ceftizoxime (Cef) and its diffusivity across the peritoneal membrane were studied in 10 chronic kidney failure patients undergoing continuous ambulatory peritoneal dialysis. Cef was determined by HPLC. The results showed that the disposition of Cef could be described with a 2 compartment open model after 1 g intravenous infusion. VD = 20 +/- 5 L, AUC = 1237 +/- 327 micrograms.ml-1.h. T1/2 beta = 16.9 +/- 4.5 h, which was much longer than that of patients with normal renal function. Therefore, the regulation of dose regimen was necessary when treating patients with renal failure. Cef was partly eliminated by peritoneal dialysis with the ClD of 2.9 +/- 1.0 ml.min-1. The bidirectional exchange of Cef was seen between blood and dialysate. It is more suitable to describe the diffusive characteristics of Cef from dialysate (or blood) into blood (or dialysate) with a zero order constant rate model. The absorption percentage of Cef after 0.5 g instilled with peritoneal dialysate was 90.4 +/- 7.0%. PMID- 1456068 TI - [Influence of dexamethasone and epinephrine on glycogen content and cytosol glucocorticoid receptors in hyperthyroid rat liver]. AB - The influence of hyperthyroidism on the action of drugs affecting rat liver glycogen content and its mechanism were investigated. The thyroid-induced hyperthyroidism of rat served as the model. In normal rats, dexamethasone (5 mg.kg-1, ip) increased the content of liver glycogen and decreased the Bmax of glucocorticoid receptors (GCR) in liver cytosol. These effects were minimized or even disappeared in hyperthyroid rat models. On the other hand, in normal rats, epinephrine (0.20 mg.kg-1, ip) decreased the content of liver glycogen. This effect was potentiated in hyperthyroid rat models. Epinephrine did not affect the Bmax of GCR in liver cytosol of normal and hyperthyroid rats. These results suggested that hyperthyroidism may be one of the causes effecting the individual differences of drug action, and that the influence of hyperthyroidism on the glycogen-increasing action of dexamethasone correlated well with the changes in glucocorticoid receptor. The mechanism of the influence of hyperthyroidism on the glycogen-decreasing action of epinephrine is to be further explored. PMID- 1456069 TI - Utilization and patterns of care in comprehensive psychiatric care organizations. A review of studies and some methodological considerations. AB - This article reviews and analyzes studies on the utilization of care and patterns of care in psychiatric care organizations with a defined catchment area responsibility. Eight studies fulfilled the inclusion criteria. The main results of the studies were reviewed with regard to distribution of utilization, typical patterns of care, sociodemographic characteristics, clinical characteristics and, when appropriate, organizational characteristics related to utilization. The results show that a small proportion of patients use a large proportion of resources. Sociodemographic factors such as living alone or having no occupation in some of the studies predicted a higher utilization. Only one study reported sex differences, men being more common among heavy users. In most of the studies a psychosis diagnosis predicted a higher utilization. A history of prior contacts with psychiatric care predicted a higher utilization in 2 studies. It is concluded that future studies should make efforts to develop standardized models of classification of patterns of care to enhance possibilities of comparisons. Cost, as a common unit for summarizing and comparing resource utilization, has not been used, but is viewed as a highly relevant measure. Furthermore, measures of utilization should be separated from evaluations of outcome or quality of care. However, the latter is a neglected area that should also be promoted in studies of utilization of psychiatric care to create knowledge of the relationship of utilization to outcome. PMID- 1456070 TI - Predicting symptoms of depression from reports of early parenting: a one-year prospective study in a community sample. AB - The purpose of this study was to determine whether (reported) parental over involvement and lack of affection identify initially healthy subjects at risk for depression. One thousand subjects from the province of Utrecht, the Netherlands were randomly selected by using telephone addresses and asked to participate in a one-year prospective study on psychological risk factors of depression. From the 108 subjects that finally participated on both occasions, the reports of parental upbringing (Parental Bonding Instrument) of initially non-depressed subjects with a Zung Self-rating Depression Scale score below 49 points were used to predict new cases of depression one year later. Initially non-depressed subjects who reported maternal over involvement in the upper quartile of the distribution had an 8.5-fold increased risk (95% confidence interval 0.9 to 80.6) of becoming depressed one year later. Although initial reports of low paternal affection were positively associated with initial symptoms of depression, this characteristic failed to show predictive value. Parental upbringing deficiencies have frequently been shown in cross-sectional inpatient studies in which retrospective retrieval from memory because of depressive state characteristics may have caused negative colouring. Our results would suggest that maternal over involvement reported in the absence of a depressed mood still proves to be an important psychological risk factor in the aetiology of depression. PMID- 1456071 TI - Factor study of the Geriatric Depression Scale. AB - A sample of 234 people between the ages of 60 and 95 was studied using the Brink Yesavage Geriatric Depression Scale (GDS). The GDS has good concurrent validity with the Hamilton Rating Scale for Depression with the Melancholia Scale (r = 0.77), which confirms the clinical utility of this scale. A factor analysis of principal components with an oblimin rotation was performed. The results obtained imply that structural validation cannot be made in relation to Beck's cognitive model of depression. It can be concluded that the elimination of the somatic items does not add any theoretical correspondence with the model, as the factors tend to group the various items into one dimension. PMID- 1456072 TI - Clusters in a cohort of untreated schizophrenia: prognostic importance, atypical cases and the familial versus sporadic distinction. AB - In search of features of prognostic importance, a cohort of patients admitted to a mental hospital in 1925 was investigated by means of multivariate clustering techniques. Using K-means cluster analysis or Q-factor analysis, a group containing cases with unfavourable prognosis was isolated. Other groups derived were prognostically heterogeneous. One group of patients, in early phases similar to good prognosis schizoaffective psychoses, could be distinguished and characterized by non-symptom items. There was initial periodicity and onset was acute. They were, on average, younger than the other subjects and there was no personality deviation or emotional disturbance before onset of disease. A family history of mental illness was rare. Two of the factors were positively and negatively characterized by items covering familial history of mental illness, thus seemingly confirming the familial vs sporadic distinction in the subclassification of schizophrenia. Though the clinical pictures were distinctively different at the time when the ratings underlying the analysis were made, approximately the same proportion of cases in the two groups had independently been diagnosed as paranoid schizophrenia--also taking the course of illness into account. It could furthermore be shown that the population at risk- siblings and children of subjects--as well as the observed number of years at risk in these groups were significantly smaller in the sporadic group than in the familial group. This was a combined effect of a lower fertility in subjects and parents in the sporadic group and a higher rate of drop out due to mortality and other reasons among siblings of these subjects. The same tendency was indicated when subjects with and without family history irrespective of factor belongingness were compared. It cannot be concluded that the familial vs sporadic distinction is without relevance in the research on schizophrenia, but its essence may easily be obscured, if the population at risk is not taken into account. PMID- 1456073 TI - Folate, vitamin B12 and cognitive impairment in patients with Alzheimer's disease. AB - This study examines the relationship between folate, vitamin B12 and severity of cognitive impairment in patients with Alzheimer's disease (AD) as compared with other disorders associated with cognitive impairment. The patients were 97 consecutive referrals to an AD clinic. Forty patients had either possible or probable AD, 31 had other dementias (OD) and 26 had mild cognitive impairment (cognitively impaired, not demented; CIND). Patients had blood drawn for serum, red cell folate and B12, as well as other biochemical indicators of nutrition, within 24 h of the Mini-Mental State Examination (MMSE). In the AD group, only B12 was significantly correlated with MMSE. Using regression analysis, B12 contributed significantly to variance in MMSE. There was no correlation between MMSE and serum, red cell folate or B12 in the OD or CIND group and no significant correlation between MMSE and other nutritional indices in any group. These findings suggest the possibility of a specific relationship between B12 levels and severity of cognitive impairment in patients with AD. PMID- 1456074 TI - Multidimensional ordering of psychopathology. A factor-analytic study using the Comprehensive Psychopathological Rating Scale. AB - The aim of the study was to search for a multidimensional order in the psychopathology of the functional mental disorders in general. A heterogeneous group of 192 patients was investigated by means of a semistructured interview based on the Comprehensive Psychopathological Rating Scale. Principal component factor analysis revealed 5 clinically meaningful dimensions interpretable as representing dysregulation of emotion and motivation, perceptual and behavioural disintegration and dysregulation of autonomic functions. PMID- 1456075 TI - Psychiatric service use: a cohort study of first attenders. AB - A retrospective cohort study was undertaken of all 1047 first-ever psychiatric service attenders to Christchurch general psychiatric services in 1981. All episodes of care were examined to the end of 1989. Only 24% of contacts were as an inpatient. Long-term contacts and frequent presenters formed only 15% of the sample. Nearly all cases not immediately discharged remained within the adult general service. Demographic and clinical variables and patterns of resource use are discussed. PMID- 1456076 TI - Depressive symptoms and depression among elderly people in Athens. AB - A total of 251 elderly residents of 2 boroughs of greater Athens were examined by a psychiatrist. For the assessment of depressive symptoms, the Center for Epidemiological Studies Depression (CES-D) Scale was used. Cognitive functioning was also evaluated. The prevalence of affective disorders of any type was estimated by a clinical examination with a semistructured psychiatric interview (PEF) supplemented by DSM-III criteria. A total of 27.1% of the elderly respondents reported a significant number of dysphoric or depressive symptoms and were identified as depressed cases. Respondents who had lower socioeconomic status, were widowed, were experiencing stressful life events or were living alone exhibited a significant degree of depressive psychopathology. An association between depressed mood and cognitive impairment was also found. A total of 9.5% of the sample was diagnosed as suffering from any type of affective disorder (1.6% major depression, 0.6% bipolar, 5.5% dysthymic disorder and 2.0% adjustment disorder with depressed mood). Affective disorders constitute nearly half of the total number of psychiatric diagnoses (20.3% at the sample). It is interesting that, of the 27.1% of the sample with depressed mood (> or = 16 score on CES-D Scale), only 9.5% of the sample were diagnosed as suffering from clinical types of depression. PMID- 1456077 TI - Saccade programming during short duration fixations: an examination of copy typing, letter detection, and reading. AB - Three experiments examined saccade programming during short duration fixations between 50 ms and 150 ms. In experiment 1, subjects copy typed text, in experiment 2, subjects read and executed a letter detection task, and in experiment 3, subjects read for comprehension only. Fixation duration had no effect on the size of the departing saccade in the copy typing task; however, saccades leaving short duration fixations were larger than saccades leaving all other fixation durations in the letter detection task and smaller than saccades leaving long fixation durations in the standard reading task. Within Morrison's (1984) model, these results imply, first, that consecutive shifts of attention during a fixation can take different directions and, second, that successive shifts of attention during a fixation support different purposes. Within Fischer's (1986, in press) model, the results imply that the engagement/disengagement of attention and saccade programming do not constitute independent events. PMID- 1456078 TI - Diagnostic classification by experts and novices. AB - The present study examines differences between experts and novices in classifying symptoms and the effect of the nature of the task on classifying. The study involved three groups of subjects, two expert groups (n = 12, n = 10) and one novice group (n = 12). Thinking-aloud protocols were collected for two classification tasks: sorting of behavioural symptoms into predefined categories and intuitive clustering of behavioural symptoms. In a third task, experts and novices were asked to make typicality ratings of behavioural symptoms. The protocols were analyzed with respect to seven cognitive operations: (a) asking or giving information, (b) associating, (c) abstracting or labelling, (d) explaining, (e) neutral matching, (f) identifying, and (g) differentiating. Results showed an effect of experience and an effect of the task on the relative frequencies of these operations. No differences were found in typicality rating of experts versus novices. These contradictory findings are discussed in relation to Kolodner's model about the evolution of expertise. PMID- 1456079 TI - Spatial attention and expectancy for colour, category and location: further evidence against the spotlight model. AB - A study of spatial attention is reported in which different colours and categories of object tended to appear at different locations. Subjects made speeded orientation judgements to alphanumeric characters that could appear either above or below the centre of a display. In the Colour Condition subjects were informed that red characters tended to appear at one location (p = 0.8), while green characters tended to appear at the other. In the Category Condition letters tended to appear at one location, and digits at the other. Before each trial subjects were cued to expect either a red or a green character (Colour Condition); or a letter or a digit (Category Condition). It was found that spatial selectivity varied according to the colour, or category of object presented. The latter finding replicated an earlier report (Lambert 1987). Spatial selectivity was appropriate for the character presented, even when it was in the uncued colour (or category). It is concluded that subjects are able to form and make use of complex attentional expectancies concerning combinations of colour with location, and category with location. Theoretical implications of these results are discussed. PMID- 1456080 TI - Enhancement of the Simon effect by response precuing. AB - When stimuli are presented to the left or right of fixation, and stimulus location is irrelevant, responses are faster if the stimulus location coincides with the location of the assigned response. This phenomenon is called the Simon effect. The present study examined the influence on the Simon effect of attentional precues that signaled the likely stimulus location and intentional precues that signaled the likely response. Experiment 1 was a close procedural replication of an experiment by Verfaellie, Bowers, and Heilman (1988); consistent with their findings, the Simon effect was enhanced by the intentional precue and unaffected by the attentional precue. Experiments 2 and 3 demonstrated the importance of the intentional precue with simpler procedures that involved only intentional and attentional precues, respectively. Finally, the intentional precuing enhancement of the Simon effect was obtained when two stimuli were assigned to each response, regardless of whether the hands were uncrossed (experiment 4) or crossed (experiment 5). Overall, the results indicate that response precuing enhances the Simon effect and favor response-selection accounts over those that attribute the effect to stimulus identification. PMID- 1456081 TI - Lost sampling units and investigational power. PMID- 1456082 TI - Biochemical parameters associated with low bone density in healthy men and women. AB - A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25 (OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women. PMID- 1456084 TI - Mechanical properties of trabecular bone within and adjacent to osseous metastases. AB - Despite radiographic and histologic evidence of trabecular bone density changes within and adjacent to osseous metastases, there currently exist no data to demonstrate whether these changes are important in predicting the risk of fracture. To determine if these density changes result in significant reductions in mechanical properties, trabecular bone specimens were prepared from lower thoracic and lumbar vertebrae from two cadavers with radiographic, gross, and histologic evidence of lytic and/or blastic osseous metastases. Each specimen was classified as normal, lytic, or blastic based on appearance in fine-grain radiographs of 8-9 mm thick coronal plane sections. Specimens were tested to failure in uniaxial compression, and tissue and apparent densities were measured. Mean tissue densities were within normal ranges. The mean apparent density for all specimens combined was within the normal range for human vertebrae, and the mean apparent density for radiographically normal (0.131 g/ml) and lytic (0.111 g/ml) specimens was less than the mean apparent density of blastic (0.182 g/ml) specimens (p < 0.02). The moduli of lytic and blastic specimens were less than for normal specimens (p < 0.025). The strength of lytic specimens was less than normal (p = 0.057), but the strength of blastic specimens was not (p > 0.1). Apparent density explained significant fractions of the variations in both modulus (p < 0.001) and strength (p < 0.001). The data suggest that blastic changes associated with osseous metastases to trabecular bone disrupt the normal dependence of trabecular mechanical properties on apparent density, but lytic changes do not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456083 TI - Transcriptional activation of c-fos and c-jun protooncogenes by serum growth factors in osteoblast-like MC3T3-E1 cells. AB - The present study was undertaken to clarify the relationship between c-fos and c jun protooncogene expression and the differentiation and/or proliferation of osteoblasts, using osteoblast-like MC3T3-E1 (E1) cells. c-fos mRNA was barely detectable, whereas c-jun mRNA was constitutively expressed in E1 cells after serum deprivation for 24-72 h. When serum was added, a rapid and transient induction of c-fos and c-jun mRNAs was observed. The c-fos and c-jun mRNAs reached peak levels at 30 minutes, with a rapid disappearance of c-fos mRNA within 3 h and a much slower decrease in c-jun mRNA. The addition of serum together with cycloheximide, an inhibitor of protein synthesis, resulted in the superinduction of both c-fos and c-jun mRNAs. Among various growth factors, PDGF, EGF, and bFGF mimicked the serum effect, whereas IGF-I and TGF-beta failed to induce c-fos and c-jun mRNA. The effects of PDGF, EGF, and bFGF were completely abolished by pretreatment with actinomycin D, an inhibitor of RNA synthesis, suggesting a transcriptional mechanism. Nuclear runoff experiments showed that the transcription rate of c-fos and c-jun protooncogenes was increased by serum and growth factors. The effects of PDGF, EGF, and bFGF were inhibited by H-7 or staurosporine, inhibitors of protein kinase C (PKC), but not by HA1004 with a much weaker inhibitory activity, suggesting the involvement of PKC for the activation of the protooncogenes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456085 TI - Osteogenesis associated with bone gla protein gene expression in diffusion chambers by bone marrow cells with demineralized bone matrix. AB - Diffusion chambers with rat bone marrow cells and demineralized bone matrix (DBM) were implanted subcutaneously to syngeneic 8-week-old rats and were harvested every week 3-7 weeks after implantation, and histochemical examination, determination of alkaline phosphatase activity, total calcium and phosphorus, the bone-specific vitamin K-dependent gla-containing protein (BGP) content, and detection of BGP mRNA relative to mineralization were performed. Alkaline phosphatase in diffusion chamber implants reached the highest activity at 4 weeks and then decreased. Calcium and phosphorus deposits occurred at 4 weeks after implantation and were followed by marked increases until 7 weeks, which was comparable to the accumulation of BGP. The BGP gene within the diffusion chambers began to be expressed at 5 weeks, and its expression increased markedly at 7 weeks after implantation. At 4-5 weeks after implantation, new bone adjacent to the membrane filters and cartilage toward the center of the diffusion chamber were observed histochemically. Light microscopic and immunohistologic examinations of chambers with marrow cells and DBM revealed production of mineralized matrices, typical of bone characterized by the appearance of BGP and mineralized nodules. In contrast, bone marrow cells alone did not show extensive bone formation and yielded very low values for these biochemical parameters. The present experiments demonstrate the potential of bone marrow cells and DBM to produce not only cartilage formation but also membranous bone formation associated with increasing expression of BGP mRNA during the later stages of bone formation, as well as a marked accumulation of BGP. PMID- 1456086 TI - Racial differences in pre- and postmenopausal bone homeostasis: association with bone density. AB - The disparity in fracture incidence and bone mass in women of European (white) and African (black) ancestry is of unknown etiology. To determine if racial differences in bone mass reflected racial differences in the mechanisms of bone turnover underlying bone mineral loss, we measured serum osteocalcin, serum alkaline phosphatase, fasting urinary calcium and hydroxyproline excretion, 24 h urinary excretion of calcium and sodium, and dietary intakes of calcium and vitamin D in 263 healthy pre-, peri-, and postmenopausal white and black women. In addition, radial and spinal bone density were measured cross-sectionally for comparison with biochemical measures of bone turnover. The biochemical parameters thought to reflect bone resorption (fasting urinary calcium and hydroxyproline excretions) were lower in black than in white women throughout the age and menopausal stages studied. The parameters thought to reflect bone formation (alkaline phosphatase and osteocalcin), were similar in the two racial groups among the premenopausal women, but osteocalcin was significantly lower among the peri- and postmenopausal blacks. Cross sectionally measured radial bone density increased with age in premenopausal black women, but it did not change with age in the white premenopausal subjects, a statistically significant difference. In peri- and postmenopausal women radial density declined significantly with years after menopause in both racial groups, but the rate of decline was significantly slower in the black women. Lumbar bone density in premenopausal white and black women did not change with age. After menopause lumbar bone density declined significantly and similarly in both racial groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456087 TI - Prostaglandin E2 alleviates cyclosporin A-induced bone loss in the rat. AB - Cyclosporine A (CsA) administered to the male and female rat produces high turnover osteopenia. Prostaglandins have both bone-resorbing and bone-forming properties, but administration of prostaglandin E2 (PGE2) to the rat in vivo produces a net increase in cancellous bone. To investigate the effects of PGE2 on CsA-induced alteration in bone mass, 43 male Sprague-Dawley rats (9 weeks old) were administered 15 mg/kg of CsA by oral gavage and/or 6 mg/kg of PGE2 by subcutaneous injection daily for 21 days according to the following protocol: group A was an age-matched control; group B received CsA only; group C received PGE2 only; and group D received CsA and PGE2. Serum was assayed on days 0, 7, 14, and 21 for bone gla protein (BGP), PTH, and 1,25-dihydroxyvitamin D [1,25 (OH)2D]. A computerized image analysis system was used for bone histomorphometry of the proximal tibial metaphysis after double tetracycline labeling. Compared to control animals (group A), treatment with CsA alone (group B) and PGE2 alone (group C) significantly elevated BGP levels. Combination therapy (group D) resulted in BGP levels that were significantly higher on days 7 and 14 than with either agent alone. 1,25-(OH)2D was significantly elevated in the CsA group only (group B). Therapy with CsA alone (group B) resulted in a significant osteopenia. The concurrent administration of PGE2 with CsA (group D) alleviated the altered bone mass induced by CsA alone by adding a significant amount of additional bone. This report confirms and extends the current knowledge of the different effects of CsA and PGE2 on bone mineral metabolism and demonstrates that PGE2 can alleviate the deleterious effects of CsA on bone. PMID- 1456089 TI - Lateral spine densitometry is a more sensitive indicator of glucocorticoid induced bone loss. AB - Osteoporosis is a common complication of glucocorticoid therapy. Bone density measurement is now commonly used in assessing which steroid-treated patients require specific interventions to reduce fracture risk. The recently developed techniques for the measurement of bone mineral density (BMD) of the vertebral body alone, by dual-energy x-ray absorptiometry (DXA) in the lateral projection, may be particularly useful in this context since steroid-induced bone loss is most marked in trabecular-rich regions like the vertebral body. This possibility has been assessed in the present study by the measurement of BMD in the lateral and anterioposterior (AP) projections in 28 women receiving chronic glucocorticoid treatment. The two BMD measurements were significantly related (r = 0.62, p < 0.001). When expressed in relation to age-appropriate normal values, lateral BMDs were lower than AP BMDs both in percentage terms (70.8 +/- 4.4 versus 90.3 +/- 2.6%, p < 0.001) and in terms of Z scores (-1.42 +/- 0.22 versus 0.91 +/- 0.24, p = 0.027). AP BMD Z scores classified 12 patients as osteopenic, whereas a further 7 were so categorized by lateral BMD Z score. It is concluded that lateral DXA scanning is a more sensitive indicator of glucocorticoid-induced osteopenia than conventional BMD measurement in the AP projection. PMID- 1456088 TI - beta-Glycerophosphate-induced mineralization of osteoid does not alter expression of extracellular matrix components in fetal rat calvarial cell cultures. AB - When fetal rat calvarial cells are cultured in medium containing vitamin C, osteoid nodules develop after approximately 15 days of culture. Upon addition of an organic phosphate (beta-glycerophosphate, beta GP), these nodules mineralize. We have now used this system to explore the suggestion made by others that a negative feedback may exist between matrix mineralization on the one hand and the synthesis of alkaline phosphatase and bone matrix collagen on the other by analyzing the synthesis of these proteins and the levels of their mRNAs in mineralizing and nonmineralizing cultures. Our results indicate that in the osteoid nodule-bone nodule system, matrix mineralization did not affect the mRNA levels for osteopontin, type I collagen, bone sialoprotein, or osteocalcin. Synthesis of total protein and collagen and the osteocalcin content of culture media were also not different in the mineralizing and nonmineralizing cultures. However, alkaline phosphatase mRNA was increased in early mineralizing cultures and alkaline phosphatase activity in the cell layer was also increased in mineralizing cultures. Thus, the hypothesis that a direct negative feedback exists between mineralization and matrix protein synthesis is not supported by our experiments. PMID- 1456090 TI - Excessive L-thyroxine therapy decreases femoral bone mineral densities in the male rat: effect of hypogonadism and calcitonin. AB - Excess thyroid hormone decreases bone mineral density (BMD), a potential problem in managing patients with differentiated thyroid carcinoma and nontoxic goiter who require lifelong TSH-suppressive doses of thyroid hormone. We studied the effect of thyroid hormone excess on vertebral and femoral BMD and the role of hypogonadism in modulating this effect in a rat model. The potential role of calcitonin (CT) in preventing thyroid hormone-associated bone loss was also investigated. A total of 40 male Sprague-Dawley rats were divided into four groups. Groups 1 and 2 were orchidectomized (ORX); groups 3 and 4 were sham operated (SO). Groups 1 and 3 received 20 micrograms intraperitoneal L-thyroxine (L-T4) per 100 g body weight daily for 3 weeks; groups 2 and 4 received vehicle IP. Another 40 rats were divided into four groups. Groups 1 and 2 received L-T4, and groups 1 and 3 received CT, 2.5 U per 100 g body weight, subcutaneously (SC) daily for 3 weeks. BMD of the L4 and 5 and the right femur were measured by dual energy x-ray absorptiometry at baseline and at the end of the study. Orchidectomy decreased femoral (P < 0.05) but not lumbar BMD. The administration of excess L T4 decreased femoral (cortical) BMD in both SO (P < 0.05) and ORX rats (P < 0.05) without affecting lumbar (trabecular) BMD. CT increased lumbar BMD in both vehicle (P < 0.001) and L-T4-treated rats (P < 0.001). However, CT did not affect femoral BMD in vehicle-treated rats and did not prevent the L-T4-induced femoral bone loss.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456091 TI - Acronyms in bone densitometry. PMID- 1456092 TI - Long-term effects of gallium nitrate in patients with Paget's disease of bone. PMID- 1456093 TI - Subdural effusions: determination of contrast medium influx from CSF to the fluid accumulation by computed tomography as an aid to the indications for management. AB - In 46 patients with subdural effusions CSF dynamics and especially the influx of contrast medium from CSF to the subdural fluid accumulation was investigated by serial computed tomography (CT). In 16 cases the subdural effusion was of traumatic and in 30 cases of non-traumatic origin. The results allowed a subdivision of the patients into three groups. Group 1: patients without contrast medium influx into the subdural fluid accumulation; group 2: patients with delayed influx; group 3: patients with immediate influx. In group 1 patients the subdural effusion acted as a space-occupying process with absolute indication for surgical treatment. Also in group 2 patients the further course showed that a surgical indication was given, because the fluid accumulation did not resolve under conservative management but increased in size, and/or the neurological deficit worsened. In all group 3 patients the subdural effusions decreased and finally disappeared conservatively. Group 1 patients with effusions on traumatic origin generally had more severe injuries than the patients of the other groups. The investigations caused no serious complications. This diagnostic method proved to be a reliable means for early differentiation between the possibility of conservative management or the indication for operative treatment in cases with subdural effusions of different origin. PMID- 1456094 TI - Craniocervical junction malformation treated by transoral approach. A survey of 25 cases with emphasis on postoperative instability and outcome. AB - An experience with 25 consecutive cases of craniocervical junction (CCJ) malformations operated upon via the transoral route is reported. Twenty-two patients also underwent posterior occipito-cervical stabilization with alloplastic material and in only one patient was transoral odontoidectomy and fusion with bone autograph performed. Indication for the transoral route consisted of an irreducible ventral compression of the cervicobulbar junction by the abnormal bone complex. Two patients died during the early postoperative period and the remaining 23 survivors were followed for an average of 3.5 years: 17 of these showed marked improvement and 5 a stabilization of the neurological disturbances. A further patient, who refused posterior stabilization, eventually died because of progressive cranial settling. Long-term results have shown this approach to be decisive in the surgical management of well-selected CCJ anomalies. PMID- 1456095 TI - Microsurgical anatomy and operative technique for extreme lateral lumbar disc herniations. AB - The anatomy of the lateral aspect of the lumbar spine and our lateral microsurgical technique for extreme lateral lumbar disc herniations (ELLDH) is described. This study was based on the microdissection of 4 cadavers, on the morphometric evaluation of these as well as 6 dried cadaver spines and 8 lumbar CT scans, and on the use of this technique on over 200 cases. Level dependent changes in the posterior arch cause a shift of the disc space distally relative to the facet joint, an increasing amount of bone to overlie the intervertebral foramen, and a decreasing amount of working space within the exposure in the caudal direction. Therefore, more bone removal from the lateral aspect of the pars interarticularis and supero-lateral aspect of the facet joint is required in the lower lumbar spine. When the exposed ligamentum flavum is resected, the dorsal root ganglion is seen and access to the herniation and disc space is achieved. Level dependent changes in the pedicles and transverse processes lead to an alteration in the course and relationships of the nerves, thereby influencing the pathophysiology of and surgical technique for the ELLDH. The operative target is the lateral aspect of the pars interarticularis and not the intertransverse space as has been previously described. Our techniques allows for the early identification of the nerve with minimal risks of injury to it, to the adjacent vessels and to the structural integrity of the facet joint and pars interarticularis. PMID- 1456096 TI - A primate model for acute and late cerebral vasospasm: angiographic findings. AB - A subarachnoid haemorrhage (SAH) in the squirrel monkey was produced by injection of blood via a permanently implanted catheter connected to the cisterna magna and a cannula stereotactically inserted into the interpeduncular cistern. Repeated angiographic examinations of the vertebro-basilar and right internal carotid arteries revealed a biphasic vasospasm with a maximal acute spasm at ten minutes and maximal late spasm at six days after blood injection. The present study has shown that a reproducible biphasic vasospasm can be produced in the squirrel monkey and evaluated by repeated angiographic examinations. The model is suitable in the study of basic mechanisms underlying vasospasm in a primate and, due to the size of the animal, autoradiographic evaluation of the cerebral blood flow and metabolism can be performed at an acceptable cost. PMID- 1456097 TI - Effect of lesioning of medullary catecholamine neurons or the median eminence on the development of cerebral vasospasm in the squirrel monkey. AB - Injections of blood into the interpeduncular fossa and cisterna magna in the squirrel monkey produce an angiographically demonstrable, biphasic cerebral vasospasm with a maximal acute spasm at ten minutes and a maximal late spasm at six days after the subarachnoid haemorrhage (SAH). Selective lesioning of the A2 nucleus in the medulla oblongata or the median eminence in the hypothalamus prior to the SAH prevents the development of both the acute and late cerebral vasospasm. The present data indicate that the A2 nucleus and the median eminence participate in the development of vasospasm in the squirrel monkey. PMID- 1456099 TI - A new model for non-invasive, reproducible fixation of a stereotaxic frame using an orthodontic resin plate. Technical note. AB - The authors describe a new method for reproducible, non-invasive fixation of a stereotaxic localizing frame. A localizing system similar to that of Brown Roberts-Wells for MR can be fixed at the base of the facial skeleton to the upper dental arch by an orthodontic resin plate. Results of trials with CT scan, advantages and disadvantages are discussed. The new fixture could be employed in open surgery and in fractionated radiotherapy. PMID- 1456098 TI - Changes in CSF pressures during experimental acute arterial subdural bleeding in pig. AB - The effects of acute arterial subdural bleeding on cerebrospinal fluid (CSF) pressure and 12 other vital parameters were studied in spontaneously breathing pigs (group 1, n = 9) and in mechanically ventilated pigs (group 2, n = 18) to analyze quantitatively the bleeding course and the lethal mechanism. Spontaneously breathing animals all succumbed after a mean bleeding volume of 45.6 +/- 8.9 ml, corresponding to about 50 per cent of the intracranial volume, and a mean bleeding duration of 11.0 +/- 2.6 min. Rapid rise in CSF pressures, marked transtentorial pressure gradients, and progressive reductions of cerebral perfusion pressure leading to a permanently iso-electric EEG, apnoea and to a terminal rise in arterial pressure (Cushing response), was the rule in these animals. The mechanically ventilated animals had smaller bleeding volumes (34.3 +/- 8.1 ml), but longer bleeding durations (13.8 +/- 5.8 min). In this group 7 animals survived. They had no pressure gradients, and only moderate changes in arterial pressure and EEG. The 11 animals that succumbed had marked transtentorial pressure gradients, but smaller increments in arterial pressure than the spontaneously breathing animals. At autopsy, subdurally located blood was found throughout the intracranial and spinal subdural compartments and along the spinal nerve roots in both groups. The results of this study suggest that survival after acute subdural haematoma is influenced by the presence of transtentorial pressure gradients and by the spinal sac acting as a space for expansion. The beneficial effect of artificial ventilation is discussed. PMID- 1456100 TI - Telescopic suction tube for microsurgery. AB - An adjustable telescopic suction tube has been developed for microsurgery. Owing to this innovation, the surgeon can easily set the suction tube to a suitable length by gently pulling the end of the telescopic tube out or in. PMID- 1456101 TI - Subcortical topography and proportions of the pyramidal tract. AB - The pyramidal tract (PT) was dissected in 30 normal human hemispheres according to the method of Klingler. The various dimensions as well as the cerebral landmarks were studied. The pyramidal tract is built up like a fan in the white matter by a thin layer of fibers of 2.8-3.5 mm in thickness. The fibers converge toward the internal capsule to a solid fiber tract with a lateral and apdiameter of 7.8 +/- 1.6 mm and 17.5 +/- 2.1 mm, respectively. This configuration of the PT presents different possibilities of damage during surgery. The evaluation of the three-dimensional course of the PT is possible by using three cerebral landmarks, the precentral gyrus, the entrance into the internal capsule and the posterior limb of the internal capsule. Their topography is described. Additionally the pyramidal tract can be defined medially by the sulcus cinguli and the roof of the lateral ventricle and laterally by the superior sulcus circularis Insulae. The possible displacement of the PT by space occupying lesions and the intra operative orientation is discussed. PMID- 1456102 TI - The termination of the vein of "Labbe" and its microsurgical significance. AB - Information about the termination of the inferior anastomotic vein of Labbe is of crucial importance in the subtemporal neurosurgical approach and its modifications. An intradural course has been observed in all cases. The vein of Labbe reaches in 3/4th the anterior third of the transverse sinus, in 73% of all cases tracing a so-called tentorial sinus. By dissecting the vein of Labbe out of its dural bed and shifting its fixation point, microsurgical access is facilitated considerably. PMID- 1456103 TI - Anterior lateral ventricular subependymal giant cell astrocytomas. Microsurgical aspects of two cases. AB - The surgical management of two cases of lateral ventricular subependymal giant cell astrocytoma, arising in the head of the Caudate nucleus, and causing hydrocephalus due to obstruction of the foramen of Monro is described. One lesion, in a patient with tuberous sclerosis, was resected using a transcallosal approach and the other, in a patient with no stigmata of tuberous sclerosis, using a frontal, trans-cortical transcystoventricular approach. The microsurgical aspects of excision and pathological anatomy of both tumours were very similar. Following tumour excision and pellucidotomy both patients had partial resolution of their hydrocephalus with complete resolution of their preoperative symptoms. The merits of transcallosal and transcortical approaches to these lesions are discussed. PMID- 1456104 TI - Endo-suprasellar teratoma with teeth formation. Case report. AB - A highly ossified teratoma was diagnosed and surgically treated in a 2-year old girl. More than 150 teeth were macroscopically identified during the operation. Pathological study established the diagnosis of mature teratoma with teeth formation. Only six analogous cases have been reported previously and only two patients survived the operation. PMID- 1456105 TI - Intracranial dermoid cysts with nasal dermal sinuses. AB - Dermal sinuses penetrating the dura are important in that they may be complicated by C.N.S. infection, and this complication can be prevented by early surgery. Although well recognised over the occiput and lumbar spine, nasal dermal sinuses extending intracranially are much rarer and have received little attention in the neurosurgical literature. Two unique cases are presented, together with a literature review, discussing the anatomy, radiology, and management of the condition. PMID- 1456106 TI - Neurosurgical publications in European journals. PMID- 1456107 TI - Lesions of the sensorimotor region: somatosensory evoked potentials and ultrasound guided surgery. AB - In 10 patients with lesions of the sensorimotor cortex cortical SEP were registered to identify the postcentral gyrus, and intra-operative ultrasound sonography served to locate the lesion. The combination of both techniques helped to find the optimal approach to the lesion. Postoperative results were considered favourable, as only one patient suffered transient postoperative deterioration, six were unchanged and in three patients the pre-operative motor deficits were improved. The combination of intra-operative ultrasound and neurophysiological identification of the sensorimotor cortex is concluded as being useful in surgery within this region. PMID- 1456108 TI - The basal interhemispheric approach for acute anterior communicating aneurysms. AB - We reviewed the surgical outcome in 85 patients with ruptured anterior communicating artery (ACoA) aneurysms, who were operated on within 72 hours of onset via a basal interhemispheric (BIH) approach (Group 1, N = 48), or an anterior interhemispheric (AIH) approach (Group 2, N = 37). The age, sex ratio and pre-operative grade (Gr) were similar for both groups. The outcome at the time of discharge was as follows for group 1: excellent or good 88%; fair, 6%; vegetative state, 2% and death 4%. For group 2, it was: excellent or good 78%; fair, 16%; vegetative state, 3%; and death, 3%. A significant correlation between admission grade and outcome was found in both groups. The outcome in group 1 was better than in group 2 for patients with a Glasgow Outcome Scale (GOS) better than fair (p < 0.07). No patient in group 1 had postoperative anosmia, but nine patients in group 2 became anosmic. The total number of complications was also significantly less in group 1. Our overall mortality rate was 4%. In conclusion, the BIH approach was more beneficial for treating acute ACoA aneurysm. PMID- 1456109 TI - Acute head injuries in the elderly. An analysis of 136 consecutive patients. AB - 136 patients older than 70 years, admitted to our neurosurgical ward directly after head trauma, were analysed. 40% of them were admitted with low GCS, below 9 points, and showed a mortality of 85%. 45 patients had intracranial mass lesions- the commonest was subdural haematoma, with a low incidence of epidural haematomas. In patients admitted with GCS above 12, mortality was 20%, mainly due to pneumonia. Satisfactory results were achieved in 30% of trauma victims. From patients with intracranial space occupying lesions and GCS below 9 points on admission practically all died, despite aggressive surgical treatment and intensive care. Thus, especially in departments with limited resources, therapy can be limited, or even no therapy may be introduced in this group. Surgical treatment can be limited only to patients who are conscious on admission. In patients with non-surgical lesions, low GCS--below 9 points--leads to mortality of 80%, and in this group we propose aggressive intensive care for 24 hours and the limitation of further "maximal" therapy only to those, who significantly improve within this period of time. If the patient has a non-surgical lesion and is conscious after trauma, aggressive treatment of extracranial complication is the most important, because brain injury can usually be well tolerated by these patients. If pneumonia or heart complications do not occur this group of old patients often have a good prognosis. PMID- 1456110 TI - Aqueous two-phase systems for biomolecule separation. AB - Over the past thirty years, aqueous polymer two-phase technology has evolved, both experimentally and theoretically, into a separation science with many useful applications in biomolecule purification and bioconversion. This paper summarizes the developments in the applications of aqueous two-phase systems to biotechnology. The main topics to be considered are the phase diagram and its characteristics, fundamentals of biomolecule partition, large-scale and multi stage aqueous two-phase biomolecule purification, and extractive bioconversions. The first topic involves a discussion of the thermodynamics of aqueous polymer two-phase formation and how it is influenced by such factors as polymer molecular weight and concentration, temperature, and salt type and concentration. Next, the theoretical and experimental aspects of biomolecule partition in aqueous two phase systems will be discussed in light of the factors which influence biomolecule partition: polymer concentration and molecular weight; temperature; salt type and concentration; the addition of charged, hydrophobic and affinity derivatives. Having reviewed the fundamentals of phase diagram formation and biomolecule partition, the next two topics are applications of aqueous two-phase technology. The first set of applications involve the large-scale extraction of proteins using one to three equilibrium stages and multi-stage purifications using countercurrent distribution, liquid-liquid partition chromatography and continuous countercurrent chromatography. The second application, and very promising area for future aqueous two-phase technology, is the extractive bioconversion which permits the simultaneous production and purification of a biomolecule. PMID- 1456111 TI - Genetics and molecular biology of telomeres. PMID- 1456112 TI - Molecular genetics of superoxide dismutases in yeasts and related fungi. PMID- 1456113 TI - Genetics of the mammalian carbonic anhydrases. PMID- 1456114 TI - The development and involution of tonsils. PMID- 1456115 TI - T-lymphocyte role in the immunological reactivity of palatine tonsil. PMID- 1456116 TI - Function and morphology of macrophages in palatine tonsils. PMID- 1456117 TI - The microvasculature of the human palatine tonsil and its role in the homing of lymphocytes. PMID- 1456118 TI - The role of integrins in tonsil. PMID- 1456119 TI - Immunological and bacteriological studies on mucosa-associated lymphatic tissue in children with SOM. PMID- 1456120 TI - Intraepithelial gamma-delta T cells in normal and hypertrophic rhinopharyngeal tonsils. PMID- 1456121 TI - A role of tonsillar lymphocyte for focal infection. With special reference to lymphocyte adhesion to vessels in dermis. PMID- 1456122 TI - Evolution of the bacterial flora in recurrent adenotonsillitis. Therapeutic implications. PMID- 1456123 TI - Interfering alpha-streptococci as a protection against recurrent streptococcal pharyngotonsillitis. PMID- 1456124 TI - Bacteriology of tonsils in children: comparison between recurrent acute tonsillitis and tonsillar hypertrophy. PMID- 1456125 TI - Functional morphology of tonsillar germinal center. PMID- 1456126 TI - Experimental study of the pathological changes of rabbit tonsils exposed to anthracite coal briquette gas. PMID- 1456127 TI - Alpha-streptococci-inhibiting beta-streptococci group A in treatment of recurrent streptococcal tonsillitis. PMID- 1456128 TI - Clinical differentiation of peritonsillar cellulitis from abscess. PMID- 1456129 TI - Influence of methods of haemostasis on the microbiology of the post-tonsillectomy fossa. PMID- 1456130 TI - Recurrent pharingotonsillitis: epidemiological observations at the Center of Preventive Medicine ORL USL BA/2. Clinical and anatomopathological situations. PMID- 1456131 TI - Role of Haemophilus influenzae and group A streptococci in recurrent tonsillar infection or hypertrophy. PMID- 1456132 TI - Microbial flora and lymphocytes in nasopharyngeal lymphatic tissue in children. PMID- 1456133 TI - The concept of focal infection of tonsil. PMID- 1456134 TI - The effect of tonsillectomy and its postoperative clinical course in IgA nephropathy with chronic tonsillitis. PMID- 1456135 TI - On arthropathy with special reference to sternocostoclavicular hyperostosis. PMID- 1456136 TI - Phylogenic and ultrastructural properties of the primitive tonsils of laboratory suncuses. PMID- 1456137 TI - Immunohistochemical comparison between multinucleated giant cells which appear frequently in the tonsils of patients with pustulosis palmaris et plantaris and in other granulomatous inflammatory lesions. PMID- 1456138 TI - IgA1 localization in tonsillar follicular dendritic cells is characteristic of IgA nephropathy. PMID- 1456139 TI - Effect of adenoidectomy on eustachian tube function. Preliminary results of a randomized clinical trial. PMID- 1456140 TI - Hypertrophy of adenoids and tubal functionality. PMID- 1456141 TI - Tonsillar hypertrophy and middle ear diseases. PMID- 1456142 TI - Significance of adenoidectomy in the treatment of secretory otitis media. PMID- 1456143 TI - Tonsil surgery in heavy snoring young children. PMID- 1456144 TI - Measurement of mesopharyngeal pressure in patients with obstructive sleep apnea. PMID- 1456145 TI - Obstructive sleep apnea in children. PMID- 1456146 TI - Obstructive sleep apnea syndrome and A&T surgery. PMID- 1456147 TI - Alveolar hypoventilation due to adenoid and tonsillar hypertrophy. PMID- 1456148 TI - Natural history of otitis media with effusion in children under six years of age. PMID- 1456149 TI - Aspects of prevention of obstructive sleep apnea syndrome in developing children. PMID- 1456150 TI - Adenoids and otitis media with effusion in children. PMID- 1456151 TI - Effects of tonsillectomy. PMID- 1456152 TI - The family physician and pathologies of the tonsils: therapeutic practices. PMID- 1456153 TI - A modern medical therapy approach to streptococcal pharyngotonsillitis. PMID- 1456154 TI - Surgery for otitis media: results of randomized clinical trials as related to clinical practice. PMID- 1456155 TI - Relationship between lymphatic and glandular tissue in the larynx. PMID- 1456156 TI - Adenotonsillectomy as correction of dentofacial growth and dysfunctions. PMID- 1456157 TI - Pidotimod in the prophylaxis of recurrent acute tonsillitis in childhood. PMID- 1456158 TI - Evaluation of immune response of Waldeyer's tissues after local stimulation with bacterial ribosomal extracts. B, T and NK lymphocyte phenotype and function. PMID- 1456159 TI - Antibiotic diffusion in tonsillar tissue. PMID- 1456160 TI - Contacts between nerves and lymphocytes in human tonsils. PMID- 1456161 TI - Allergic tonsillitis. A histopathological study. PMID- 1456162 TI - Electron microscope observations on the nasopharyngeal tonsil in children with allergic rhinosinusitis. PMID- 1456163 TI - Three-dimensional ultrastructure of the secondary nodule of the human palatine tonsil. PMID- 1456164 TI - High endothelial venules in the developing human palatine tonsil. PMID- 1456165 TI - Structure of the palatine tonsil in European insectivores. PMID- 1456166 TI - Immunology and immunopathology of tonsils. PMID- 1456167 TI - Antigen-presenting cells in the nasopharyngeal tonsil. A quantitative immunohistochemical study. PMID- 1456168 TI - HLA-DR antigen expression in tonsillar epithelium. PMID- 1456169 TI - Immunohistological studies on immunocompetent cells in palatine tonsil. PMID- 1456170 TI - Diamine oxidase activity and related substrates in rat liver after chronic ethanol feeding. AB - Chronic ethanol feeding as 12% or 36% of total calories caused a dose-dependent diminution of diamine oxidase activity in rat liver. Hepatic cadaverine and histamine levels were unmodified by ethanol, whereas putrescine increased, partially in relation to the decrease in diamine oxidase activity. Such results may be of interest in view of an aggravation of ethanol-induced hepatic damage when exogenous diamines and polyamines reach the liver in potentially toxic amounts. PMID- 1456171 TI - The clearance rate of plasma kallikrein by the liver increases during the acute phase response to inflammation. AB - The effect of the acute-phase response on the clearance rate of plasma kallikrein by the exsanguinated liver was studied in three groups of rats: a control group and two other groups that received either turpentine or an endogenous pyrogen preparation. The plasma kallikrein clearance rates were significantly higher in both inflamed groups. PMID- 1456172 TI - Hepatoprotective effects of lobenzarit disodium on acetaminophen-induced liver damage in mice. AB - We have studied the effects of the immunomodulator drug lobenzarit in the model of acute hepatotoxicity induced by a high oral dose (600 mg/kg) of acetaminophen in mice. Lobenzarit at doses of 25, 50 and 100 mg/kg i.p. decreased significantly the activity of alanine aminotransferase in serum, which was increased by acetaminophen alone, and increased the concentration of reduced glutathione in mice liver, which is depleted by acetaminophen. Lobenzarit also reduced liver damage induced by acetaminophen in mice, which was observed by electron microscopy. The hepatoprotective effects of lobenzarit were dose-dependent and they were produced when lobenzarit was administered 30 min before acetaminophen or 2 and 4 h after it. It is concluded that lobenzarit exerts some effects which resemble those of an antidote of acetaminophen such as N-acetylcysteine. PMID- 1456173 TI - The role of 5-hydroperoxyeicosatetraenoic acid in neutrophil activation. AB - 5-Hydroperoxyeicosatetraenoic acid (5HPETE) has been recently reported to play an important role in regulating and modulating neutrophil function. In order to clarify the mechanism of neutrophil activation by 5HPETE, we have measured the cytosolic free calcium, which is thought to be necessary for neutrophil activation using fura-2-loaded human neutrophils. Low concentration of 5HPETE, which is thought to be produced during cell activation, had minimal effect on cytosolic free calcium by itself but dose-dependently augmented FMLP-stimulated increase in cytosolic free calcium in the presence or absence of extracellular calcium without converting to LTB4. 5HPETE had no effect on 3H-FMLP binding to human neutrophils. The present data suggested that 5HPETE would augment FMLP stimulated increase in cytosolic free calcium by enhancing the influx of extracellular calcium and/or the release of calcium from intracellular pool, which resulted in augmentation of neutrophil activation by primary agonist such as FMLP. PMID- 1456174 TI - Hypoxia/reoxygenation stimulates endothelial cells to promote interleukin-1 and interleukin-6 production. Effects of free radical scavengers. AB - Vascular endothelium produces and/or interferes with various cytokines. Previous studies have demonstrated interactions of these inflammatory and immunological mediators with oxygen-derived free radicals. The present work examines the relationship between hypoxia/reoxygenation (H/R) and cytokine production by cultured endothelial cells. Human umbilical vein endothelial cell (HUVEC) monolayers were incubated for 24 h in normoxia or submitted to 5 h hypoxia/19 h reoxygenation. Then, interleukin-1 (IL-1) alpha and beta, and interleukin-6 (IL 6), were measured in culture supernatants by specific enzyme immunoassays and bioassays, respectively. Under these conditions, the spontaneous production of IL 1 and IL-6, detected in normoxic HUVEC, greatly increased after H/R treatment. The observed enhancement was cycloheximide-sensitive and, consequently, reflected a de novo protein synthesis. Superoxide dismutase and glutathione peroxidase prevented H/R-induced IL-1 and IL-6 increase. These results constitute the first demonstration that H/R stimulates HUVEC to promote IL-1 and IL-6 production and strongly suggest a role for oxygen-derived free radicals in the cytokine synthesis. PMID- 1456175 TI - Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure. AB - Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing. PMID- 1456176 TI - A synthetic peptide metalloproteinase inhibitor, but not TIMP, prevents the breakdown of proteoglycan within articular cartilage in vitro. AB - IL1-stimulated pig articular cartilage fragments were cultured in the and absence of various metalloproteinase inhibitors. Tissue inhibitor of metalloproteinases (TIMP) was unable to stop the release of proteoglycan from the cartilage. Incubation of cartilage with a potent synthetic metalloproteinase inhibitor inhibited the release of proteoglycan in a dose-dependent fashion. The results suggest that low-M(r) metalloproteinase inhibitors may have therapeutic potential in limiting connective tissue breakdown in conditions such as rheumatoid arthritis. PMID- 1456177 TI - The effect of hyaluronan on interleukin-1 alpha-induced prostaglandin E2 production in human osteoarthritic synovial cells. AB - An in vitro study on the effects of hyaluronan (HA) on interleukin-1 alpha induced prostaglandin E2 (PGE2) production in human osteoarthritic synovial cells indicated that PGE2 induction was suppressed by HA in a dose- and molecular weight-dependent manner. PMID- 1456178 TI - Protein kinase C inhibits stimulation of adenylate cyclase by the histamine H2 receptor in rat parietal cells. AB - The action of protein kinase C on the stimulation of adenylate cyclase activity by the histamine H2 receptor was investigated in rat parietal cells. Protein kinase C was activated by preincubating cells with 12-O-tetradecanoylphorbol 13 acetate (TPA), and adenylate cyclase activity was measured in sonicated extracts. TPA (100 nM) inhibited adenylate cyclase activity stimulated by histamine (100 nM 500 microM). This effect was related to the concentration of TPA. TPA (100 nM) enhanced the stimulation of adenylate cyclase activity by forskolin (100 microM) but had no effect on the stimulation by NaF (10 mM). In conclusion, protein kinase C inhibits stimulation of adenylate cyclase by the histamine H2 receptor. This action could be mediated by changes in the number of affinity of histamine H2 receptors or in the coupling of the receptor to the stimulatory guanine nucleotide regulatory subunit Gs. PMID- 1456179 TI - The effect of WEB 2086 on PAF-induced eosinophil chemotaxis and LTC4 production from eosinophils. AB - We investigated the effect of WEB 2086, a selective platelet-activating factor (PAF) receptor antagonist, on PAF-induced eosinophil chemotaxis and LTC4 production. WEB 2086 inhibited PAF-induced eosinophil chemotaxis in normals and asthmatics. To further determine if WEB 2086 is a selective PAF receptor antagonist, we examined the effect of WEB 2086 against formyl-methionyl-leucyl phenylalanine (fMLP)-induced or eosinophil chemotactic factor of anaphylaxis (ECF A)-induced eosinophil chemotaxis. WEB 2086 did not have a significant inhibition against fMLP or ECF-A-induced eosinophil chemotaxis. These results suggest that WEB 2086 is a selective and potent inhibitor of PAF-induced eosinophil chemotaxis and LTC4 production from eosinophils, due to its antagonism of PAF-receptors. PMID- 1456180 TI - Effects of capsaicin on cutaneous vasodilator responses in humans. AB - The neurovascular responses to noxious electrically evoked axon reflex (EAR) stimulation and iontophoretic application of endothelium-dependent [acetylcholine (ACh)] and independent [sodium nitrite (NaNO2)] vasodilator substances were examined in human forearm skin using laser Doppler flowmetry, before and after repeated topical applications of the neurotoxin capsaicin (chronic capsaicin pre treatment). Following 3 or 4 days of capsaicin pre-treatment the normal vasodilator response to acute application of capsaicin was significantly reduced as was the EAR response. There were, however, no significant changes in the vasodilator responses to either ACh or NaNO2, suggesting that the neurogenic axon reflex is in series with the endothelial and microvascular smooth muscle mechanisms of vasodilatation. Recovery of normal EAR occurred within 2-4 weeks of cessation of capsaicin pre-treatment. PMID- 1456181 TI - Characterization and pharmacological modulation of soluble phospholipase A2 generated during glycogen-induced rat peritonitis. AB - Soluble phospholipase A2 (PLA2) activity was assessed in rat peritoneal lavage fluid after an intraperitoneal injection of 6% glycogen. Enzyme activity immediately increased 5-fold above basal by 4 h. Activity decreased by only 30% at 18 h and remained at this elevated level through 72 h. The initial rise in PLA2 activity was coincident with protein extravasation but not with polymorphonuclear leukocyte infiltration, suggesting that the early PLA2 activity could be, in part, blood-derived. Mononuclear cell influx occurred later (4 h), peaked by 6-8 h but remained elevated through 72 h possibly contributing to the persistence of PLA2 activity through 20-72 h. The exudate PLA2 measured at 4-6 h (early) and 20-24 h (late), after glycogen administration, were biochemically compared. They were found to be neutral pH active, Ca(2+)-dependent and were similarly inhibited by the inhibitors, p-bromophenacylbromide, ellagic acid, gossypol and luffariellolide. Oral administration of dexamethasone to rats inhibited the appearance of PLA2 activity in the peritoneal lavage fluid as well as cellular influx and protein extravasation. Indomethacin had no effect on these parameters. These studies demonstrate that PLA2 is an integral component of glycogen-induced peritonitis and can be pharmacologically manipulated. PMID- 1456182 TI - A low molecular weight component derived from the milk of hyperimmunised cows suppresses inflammation by inhibiting neutrophil emigration. AB - An earlier study demonstrated that hyperimmunisation of dairy cows with a polyvalent bacterial vaccine stimulated the secretion of a small molecular weight anti-inflammatory moiety in the milk. This hyperimmune milk factor (HIMF) has been further investigated in the present experiments. HIMF was found to suppress the cellular phase of the response to carrageenin and also the neutrophil dependent reverse passive Arthus reaction. These results, together with the observation that the administration of HIMF led to an increase in the number of circulating neutrophils, suggested that the agent might inhibit inflammation by interfering with the ability of neutrophils to emigrate from the vasculature. In vivo studies carried out to evaluate this possibility demonstrated that HIMF suppressed neutrophil emigration by up to 75%. In vitro experiments established that the ability of neutrophils to respond to chemotactic stimuli or adhere to endothelial cells was not affected by HIMF. It is possible, therefore, that the agent modulates inflammation by down-regulating the synthesis of inducible pro inflammatory cytokines or adhesion molecules. Attempts are presently being made to isolate the active moiety to allow the activity of the agent at the molecular level to be studied in more detail. PMID- 1456183 TI - Oral, anti-inflammatory activity of a potent, selective, protein kinase C inhibitor. AB - The protein kinase C family of enzymes is thought to be important in mediating signal transduction. Ro 31-8830 is a novel, potent inhibitor of protein kinase C, derived from the non-selective protein kinase inhibitor staurosporine. In this paper we demonstrate the selectivity of Ro 31-8830 for protein kinase C over other protein kinases and its ability to inhibit protein kinase-C-mediated events in platelets and lymphocytes. In addition, we describe a novel system for the in vivo evaluation of inhibitors of protein kinase C, and we demonstrate the oral anti-inflammatory activity of Ro 31-8830. This finding has implications for the treatment of inflammatory disorders in the clinic. PMID- 1456184 TI - Antiarthritic profile of BF-389--a novel anti-inflammatory agent with low ulcerogenic liability. AB - BF-389, dihydro-4-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-methyl-2H-1,2- oxazin-3(4H)-one, is a potent, orally active, antiarthritic and analgesic agent with low ulcerogenic potential. A comparison of the activity profiles of BF-389 and naproxen showed similarities in: (1) suppression of developing and chronic adjuvant arthritis (AA); (2) maximal inhibitory response, as shown by the E(max) values in the developing and established AA models; (3) inhibition of bone degenerative changes associated with chronic adjuvant arthritis; and (4) analgesic activity in the acetic acid and phenylquinone writhing assays. Though BF-389 has been shown to be a potent inhibitor of cyclooxygenase, IC50 = 0.84 +/- 0.25 microM against the production of PGE2 in vitro, there is a great difference from most cyclooxygenase inhibitors; it also inhibits the 5-lipoxygenase enzyme. For BF-389, the IC50 for in vitro LTB4 formation was found to be 3.65 +/- 1.19 microM. The ulcerogenic potential of BF-389 was compared to that of naproxen using a five-day in vivo ulcerogenic rat assay. The UD50 for naproxen was found to be approximately 30 mg/kg/day, p.o. Based upon efficacy in the DEV AA and EST AA models, UD50/ED50 values for naproxen were estimated to be 0.7 and 1.9, respectively. For BF-389 the UD50 was shown to be 520 (389-695) mg/kg/day, p.o., and the corresponding UD50/ED50 values were calculated to be 84 and 28, respectively, thus demonstrating the wide margin of safety between efficacy and ulcerogenicity in rats. PMID- 1456185 TI - Suppression of pulmonary granulomatous inflammation by immunomodulating agents. AB - We demonstrated previously that macrophages and macrophage-derived cytokines including lymphocyte-activating factors (LAFs) play a critical role in lung granuloma formation in mice and that granulomas sizes correlated with LAF activity in the lesions. In the present study, we examined the effects of D penicillamine (D-Pc), 2-acetylthiomethyl-3-(4-methyl-benzoyl)propionic acid (KE 298) and dexamethasone (Dex) on dextran bead-induced lung granulomas in mice. KE 298 is a newly synthesized compound containing sulfur (S) similar to D-Pc. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous lung extracts of the mice contained high levels of LAF that were correlated with granuloma sizes. The lesions and local LAF activity were inhibited by administration of these agents. The most potent inhibitor was Dex. The suppressive effect of KE-298 was similar to that of D-Pc. These results suggest that suppression of granulomas may be attributed to inhibition of LAF activity/synthesis by these agents. PMID- 1456186 TI - Structural and functional changes of blood-brain barrier and indication of prion amyloid filaments in experimental amyotrophic leucospongiosis. AB - The reproduction of amyotrophic leukospongiosis (AL) agent in the central nervous system (CNS) of guinea pigs was accompanied by local disturbance of blood-brain barrier (BBB), which manifested in passing of horseradish peroxidase through the endothelium of some of capillaries (10-14%). The disturbance of BBB function coincided with dystrophic changes in a number of pericapillary astrocyte foot processes and in pericytes. In the walls of altered vessels we observed congophilic (amyloid) deposits, which formed immunocomplexes with monoclonal antibodies to the AL agent protein PrP 27-30 kD. By electron microscopic the deposits consisted of masses of filaments with diameter of 5-10 nm located between the basement membrane and endothelium of the vessels. PMID- 1456187 TI - Alcohol: yesterday and today have we changed? PMID- 1456188 TI - Addiction--a family affliction. PMID- 1456189 TI - Fluidotherapy. Clinical applications and techniques. PMID- 1456190 TI - The crisis of rising health care cost: a physician's perspective. PMID- 1456191 TI - Breast feeding after cosmetic breast surgery. PMID- 1456192 TI - Culture and antigen detection tests for streptococcal tonsillopharyngitis. PMID- 1456193 TI - Culture and antigen detection tests for streptococcal tonsillopharyngitis. PMID- 1456194 TI - Diary of a week in practice. PMID- 1456195 TI - Combining insulin and oral agents in diabetes: indications and controversies. AB - Patients with noninsulin-dependent diabetes demonstrate peripheral insulin resistance that is aggravated by increased hepatic glucose production and results in elevated serum insulin and serum glucose levels. These levels can be affected by intensive diabetic management, including diet, exercise, lifestyle modifications and insulin or sulfonylurea therapy. Sulfonylureas stimulate endogenous insulin production, increase peripheral sensitivity to insulin and suppress hepatic glucose production. In spite of its added expense, increased potential for side effects and questionable efficacy, combination therapy with insulin and a sulfonylurea is often considered in noninsulin-dependent diabetics with difficult-to-control disease. PMID- 1456196 TI - Mercury toxicity. Agency for Toxic Substance and Disease Registry. AB - Because mercury has several forms and because it produces subtle effects at chronic low-level exposures, mercury toxicity can be a difficult diagnosis to establish. Elemental mercury vapor accounts for most occupational and many accidental exposures. The main source of organic methyl mercury exposure in the general population is fish consumption. Children are at increased risk of exposure to elemental mercury vapor in the home because it tends to settle to the floor. The chemical and physical forms of mercury determine its absorption, metabolism, distribution and excretion pathways. The central nervous system and kidneys are key targets of mercury toxicity. Chelation therapy has been used successfully in treating patients who have ingested mercury salts or inhaled elemental mercury. There is no antidote for patients poisoned with organic mercury. PMID- 1456197 TI - Evaluation of fetal arrhythmias. AB - Fetal arrhythmias occur in approximately 1 to 3 percent of all pregnancies. Successful management depends on early identification and evaluation. Arrhythmias are classified as irregular, bradycardiac or tachycardiac. With proper monitoring, fetuses with irregular arrhythmias can usually be delivered by family physicians. For fetuses with bradyarrhythmias or tachyarrhythmias, referral to a high-risk specialists for ongoing fetal surveillance and delivery is necessary. PMID- 1456198 TI - Clinical and imaging evaluation of the solitary pulmonary nodule. AB - Management of a solitary pulmonary nodule remains a common clinical problem. The main goal of management is to choose a diagnostic and therapeutic scheme that is appropriately matched to the patient's clinical risk of malignancy. Clinical risk can be estimated from consideration of data on the overall prevalence of malignancy in solitary pulmonary nodules in various populations, the size of the pulmonary nodule, the patient's age and the patient's history of smoking. Nodules that have not grown for at least two years and those that are calcified are usually benign and require no further work-up. Suspicious nodules require further evaluation. The approach for patients at low clinical risk for malignancy may be clinical and radiographic observation, while that for patients at moderate to high risk for malignancy may be needle biopsy or thoracotomy. Whenever possible, the patient should be encouraged to participate in the decision-making process concerning the management of this clinical problem. PMID- 1456199 TI - Clarithromycin is effective against M. avium complex in AIDS. PMID- 1456200 TI - Healthy people 2000 initiative. PMID- 1456201 TI - AAP updates cholesterol guidelines for children. PMID- 1456202 TI - Approval for broader use of DDI. PMID- 1456203 TI - Occupational and environmental hygiene; more than just a name game. PMID- 1456204 TI - Comparative testing of an FTIR remote optical sensor with area samplers in a controlled ventilation chamber. AB - A portable Fourier transform infrared remote optical sensing spectrometer was deployed and tested in a constant ventilation test chamber by using a tracer gas source. Continuous beam path measurements were collected and compared to air samples obtained from a computer-controlled, multiple-point sampling array connected to a flame ionization detector. Measurements were gathered at two different room ventilation rates and at two different dispersion conditions. A homogeneous dispersion condition had a uniform tracer concentration over the beam path and an inhomogeneous dispersion condition had a nonuniform tracer concentration distribution over the length of the beam path. Overall, the beam measurements and the point sample readings showed good agreement regardless of the room ventilation rate. Comparative data obtained from the inhomogeneous dispersion conditions did have higher variability, probably as a result of the different spatial and temporal resolution of the two sampling techniques. The tests demonstrate that a remote sensing system can be applied to an indoor room scale setting, but the dispersion of contaminant in the beam path is an important factor to consider when interpreting the beam data. PMID- 1456205 TI - An investigation of dust generation by free falling powders. AB - To identify the dust generation processes, aluminum oxide powder was dropped as a free falling slug in a test chamber. The effect of the slug's mass, diameter, and drop height upon the aerosol concentration and size distribution was measured with an aerodynamic particle sizer. To differentiate between aerosol generated during the free fall and at the end of the fall, the slug was dropped either onto a flat surface or into a container of water that suppressed dust generation associated with the impact at the end of the fall. Aerosol generation occurred during the slug's free fall as well as at the end of the fall. The falling solid induced an airflow that followed the falling solid to the end of the fall. This induced airflow contained the aerosol generated during the free fall. At the end of the free fall, the induced airflow, combined with air jets created on impact, dispersed the aerosol throughout the test chamber. Additional measurements were made by using "neutral buoyancy" helium-filled bubbles to visualize the airflow in the test chamber. The airflow and ensuing turbulence were sufficient to keep large, inspirable particles suspended throughout the test chamber for periods greater than 10 min. During experimental work, the effect of drop height, mass, and slug diameter upon aerosol generation by a single slug of powder was studied. The results indicated that the manner in which a powder is handled may be as important as material dustiness as measured by a dustiness tester. Aerosol generation can be reduced by minimizing the contact between the falling powder and the air. PMID- 1456206 TI - An assessment of critical anthropometric dimensions for predicting the fit of a half-mask respirator. AB - The purpose of this study was to determine if facial dimensions for a group of subjects were predictive of the fit factors measured while one brand of half-mask respirator was worn. Fit factors and 12 facial dimensions measured on 30 female and 38 male subjects were analyzed by correlation coefficients; weighted, multiple linear regression; and discriminant analysis. Data were analyzed for all subjects, gender subgroups, a race subgroup (whites only), and race/gender subgroups. Significant correlation coefficients with the log-transformed fit factors were found for four dimensions; four dimensions had significant coefficients in four or more multiple linear regression models. Only two dimensions had significant coefficients in four or more discriminant analysis models. Menton-subnasale (lower face) length was the only dimension included in all three of these groups. Gender-specific regression models had very high coefficient of determination values (R2 > 0.85). Discriminant analysis of the data for all subjects and race/gender subgroups found very good predictive scores for statistical software-generated models and menton-subnasale length alone; these scores were significantly better than those for the model with the respirator test panel dimensions (face length and lip width). These analyses found that facial dimensions were good predictors of respirator fit for those subjects wearing one brand of half-mask respirator. Lower face length was consistently indicated as being correlated or associated with fit. These results would indicate that dimensions other than those currently used may be more appropriate to define a half-mask respirator test panel. PMID- 1456207 TI - Hydrocarbon exposures at petroleum bulk terminals and agencies. AB - Occupational exposures to the 55 hydrocarbon components of gasoline and petroleum products were measured at the bulk terminals and agencies of six Ontario petroleum companies during the summer of 1986. A total of 82 long-term (full shift) and 111 short-term personal samples were taken over 3 months. The data, expressed as concentrations in milligrams per cubic meter, were highly variable and appeared to fit the lognormal distribution well. Full-shift exposures of bulk terminal drivers, agency drivers, and plantmen to total hydrocarbons (THC), computed as an n-hexane equivalent, and other hydrocarbon components for which exposure limits exist can be expected to exceed their respective 1986-1987 threshold limit value-time-weighted average (TLV-TWA) no greater than 1% of the time on the basis of the lognormal model. The short-term THC exposures of agency truck drivers can be expected to exceed the 1986-1987 TLV-short-term exposure limits about 7% of the time while top-loading and more than 17% while off loading. For benzene, the short-term exceedance percentages are 1% and 4% for top and off-loading operations, respectively. For long-term benzene exposures, up to 69% of the assessments can be expected to exceed the 1990-1991 proposed TLV-TWA of 0.3 mg/m3 (0.1 ppm). The full-shift hydrocarbon exposures of agency drivers were significantly higher than those for bulk terminal drivers. At the bulk terminals, the short-term hydrocarbon exposures during top-loading were significantly higher than during bottom-loading. PMID- 1456208 TI - Evaluation of eight bioaerosol samplers challenged with aerosols of free bacteria. AB - The need to quantify airborne microorganisms in the commercial microbiology industry (biotechnology) and during evaluations of indoor air quality, infectious disease outbreaks, and agriculture health investigations has shown there is a major technological void in bioaerosol sampling techniques to measure and identify viable and nonviable aerosols. As commercialization of microbiology increases and diversifies, it is increasingly necessary to assess occupational exposure to bioaerosols. Meaningful exposure estimates, by using area or environmental samplers, can only be ensured by the generation of data that are both precise and accurate. The Andersen six-stage viable (microbial) particle sizing sampler (6-STG) and the Ace Glass all-glass impinger-30 (AGI-30) have been suggested as the samplers of choice for the collection of viable microorganisms by the International Aerobiology Symposium and the American Conference of Governmental Industrial Hygienists. Some researchers consider these samplers inconvenient for evaluating industrial bioprocesses and indoor or outdoor environments. Alternative samplers for the collection of bioaerosols are available; however, limited information has been reported on their collection efficiencies. A study of the relative sampling efficiencies of eight bioaerosol samplers has been completed. Eight samplers were individually challenged with a bioaerosol, created with a Collison nebulizer, of either Bacillus subtilis or Escherichia coli. The samplers were evaluated under controlled conditions in a horizontal bioaerosol chamber. During each experimental run, simultaneous samples were collected with a reference AGI-30 to verify the concentration of microorganisms in the chamber from run to run and day to day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456209 TI - American Association of Orthodontists Foundation Endowment Fund Campaign. PMID- 1456210 TI - Comment on TMJ case report. PMID- 1456211 TI - Further comment on TMJ case report. PMID- 1456212 TI - Comment on differential tooth movement. PMID- 1456213 TI - Growth changes and orthodontic treatment in a patient with condylolysis. AB - A patient with acquired bilateral degeneration of the mandibular condyles was treated orthodontically. The flattening of condyles and the shortening of the ramus began at adolescence. The facial profile changed to a convex type, with a marked mandibular retrognathia and severe Class II malocclusion. The cause seems to be due to a condylolysis of the mandible. PMID- 1456214 TI - The effects of infraocclusion: Part 2. The type of movement of the adjacent teeth and their vertical development. AB - This second article discusses how the inclusion of a vertical component (the infraocclusion of the deciduous molar) into the otherwise horizontal band of transseptal fibers affects the vertical development of the two adjacent teeth. From the hypothesis proposed in the first article of this series, it seemed logical to assume that the occlusal heights of the teeth adjacent to the affected tooth would themselves be lowered, when measured to the inferior border of the mandible and compared with the height of the occlusal table of the control side. Secondly, since the vertical component affects only one side of each adjacent tooth, these teeth would be tilted about a center of rotation which is much higher (coronal) than is seen in a tooth that merely tips forward as the result of available space in the immediate vicinity in the arch. In this study, both these assumptions were confirmed, with a very high degree of statistical significance. PMID- 1456215 TI - The effect of corticosteroid-induced osteoporosis on orthodontic tooth movement. AB - The purpose of this research was to study the effect of corticosteroid-induced osteoporosis on orthodontic tooth movement and relapse. Sixteen 3-month-old New Zealand white rabbits were divided into four equal groups, two treatment and two control. All treatment rabbits were administered daily injections of 15 mg/kg cortisone acetate for 4 days before and during the experimental period. An orthodontic appliance delivering a mesial force of 4 ounces was placed on the maxillary left first molar of all animals. For all groups, measurements of active tooth movement were made after 4, 7, 11, and 14 days. For two of the groups, appliances were removed on day 14, and additional measurements of relapse were made through day 21. With the use of radiodensitometric readings of the humerus bone and histology of the maxilla, osteoporosis was demonstrated in the treatment animals. Mean incremental and cumulative active tooth movement was three to four times greater (p < 0.0001) in the treatment rabbits than in the controls. The treatment group in which relapse was measured demonstrated 100% relapse on day 18, whereas the control group relapsed at a much lesser rate through day 21 and never achieved 100% relapse. Histologic findings appeared to support tooth movement results. In conclusion, the results of this study indicate that rabbits subjected to corticosteroid-induced osteoporosis undergo significantly more rapid orthodontic tooth movement and subsequent relapse than control animals. PMID- 1456216 TI - Changes in lower third molar position in the young adult. AB - Changes in position of unerupted lower third molars between 18 and 21 years were examined in a group of 17 men and 24 women with intact lower arches. Mesiodistal third molar angulation, molar space, molar space condition, and buccolingual third molar angulation and the changes in these dimensions were measured on 60 degree cephalograms taken at 18 and 21 years. At 18 years molar space was inadequate by an average of 5.0 mm. Average changes in dimensions were statistically nonsignificant except for an increase in molar space of 0.7 mm. Changes in third molar position ranged from 39 degrees to -46 degrees in the mesiodistal and from 24 degrees to -24 degrees in the buccolingual dimension. Only 10 third molars did not change their mesiodistal angulation. Four third molars erupted fully during the observation period. PMID- 1456217 TI - An evaluation of the nasolabial angle and the relative inclinations of the nose and upper lip. AB - The purpose of this study was to develop a consistent and reproducible method of constructing a nasolabial angle that would also permit an evaluation of the relative inclination of the lower border of the nose and the upper lip, as well as their relationship to each other. Comparison of repeated individual measurements of soft tissue profile landmarks on 15 subjects, as completed by four orthodontists, revealed that the proposed method of constructing the nasolabial angle was consistent and reproducible by the same orthodontist and among different orthodontists. Normative data for the three nasolabial parameters were produced from a sample of 104 young white adults determined by the authors to have well-balanced faces. Mean and standard deviation values from this pooled sample demonstrated a lower border of the nose to Frankfort horizontal plane angle at 18 degrees +/- 7 degrees, upper lip to Frankfort horizontal plane angle 98 degrees +/- 5 degrees, and nasolabial angle 114 degrees +/- 10 degrees. No statistically significant difference was demonstrated between the values for men and women in this study, but the women did have a slightly larger nasolabial angle. A linear comparison of the three nasolabial parameters with six skeletal measurements revealed no significant relationship between the soft tissue profile of the nasolabial region and the underlying skeletal relationships. PMID- 1456218 TI - Comparisons of postsurgical stability of the LeFort I maxillary impaction and maxillary advancement. AB - The purpose of this study was to determine retrospectively the stability of the LeFort I osteotomy after a one-piece maxillary impaction or advancement. Cephalograms of 31 patients were evaluated before surgery, immediately after surgery, in fixation, and after fixation. Descriptive statistics for the absolute and the relative changes of the various linear and angular parameters were calculated for the different stages. The analysis of variance general linear models procedure was used to compare the impaction group (n = 23) with the advancement group (n = 8). The findings indicated that the two groups could be studied independent of age, sex, surgeon, the presence of pretreatment open bite, and the length of the postsurgical fixation. The findings further indicated the presence of significant differences in the postsurgical changes between the maxillary impaction and the maxillary advancement groups. As an example, during fixation, the maxilla moved superiorly more at point A in the advancement group (mean = 1.89 mm) than in the impaction group (mean = 0.67 mm). The upper incisor movements showed a similar pattern, moving more superiorly for the advancement group (mean = 2.30 mm) than for the impaction group (mean = 0.96 mm). Therefore care should be taken to avoid "burying" the incisors beneath the lip in patients undergoing maxillary advancement, who have minimal exposure of the maxillary incisors before surgery. PMID- 1456220 TI - The effect of acetylsalicylic acid on orthodontic tooth movement in the guinea pig. AB - This study examined the influence of acetylsalicylic acid an inhibitor of prostaglandin synthesis, on orthodontic tooth movement induced with light spring forces in the guinea pig. The animal model was shown to permit reliable and accurate recording of tooth movement up to 28 days. Tooth movement was found to be highly correlated with spring forces, indicating that the model provided a sensitive test of the effect of aspirin on tooth movement. Aspirin was administered orally at the rate of 65 mg/kg per day in three divided doses and was found to effectively inhibit prostaglandin synthesis at the level of the bronchioles. However, aspirin did not appear to significantly affect tooth movement. Thus prostaglandins may not be the only mediators of the bone resorption associated with tooth movement induced by light orthodontic forces under these experimental conditions. PMID- 1456219 TI - Superior repositioning of the maxilla combined with mandibular advancement: mandibular RIF improves stability. AB - Postsurgical changes in 24 patients who had rigid internal fixation (RIF) of the mandible with screws after combined superior repositioning of the maxilla and mandibular advancement were compared with 53 patients who underwent the same surgery but who had intraosseous wire fixation, skeletal suspension wires, and 8 weeks of maxillomandibular fixation (MMF). During the first 8 weeks after surgery, the mean posterior relapse of the mandible was greater in the MMF group than in the RIF group (for example, -1.1 mm versus 0.15 mm at B point), and the percentage of patients with clinically significant vertical and horizontal changes was greater in the MMF group. By 1 year, there had been slight additional mean relapse in the MMF group (-1.5 mm net relapse at B point, with 42% of the patients showing 2 mm or more relapse). In the RIF group, the mandible was more likely to be repositioned forward than posteriorly (net mean change at B point, 0.7 mm forward; 33% had 2 mm or more forward movement). In the RIF group, all but one of the patients (96%) were judged to have an excellent clinical result; in the MMF group, the corresponding figure was 60%. PMID- 1456221 TI - An introduction to computerization of the orthodontic practice: practice and communications systems. AB - This article is the result of an extensive investigation into currently available computer software and hardware systems. It is designed to present an overview of the options that are available, what to reasonably expect computer systems to do and not to do, and to introduce the reader to the terminology of the computer world to assist in evaluating and selecting appropriate software and hardware for office use. PMID- 1456222 TI - The pain and discomfort experienced during orthodontic treatment: a randomized controlled clinical trial of two initial aligning arch wires. AB - A randomized controlled clinical trial was performed to compare the nature, prevalence, intensity, and duration of pain related to the use of a relatively recently developed superelastic arch wire and a more traditional multistranded steel arch wire. Other factors likely to influence the pain experience were also investigated. Forty-three subjects participated in the study, the pain response being assessed by each of the visual analogue scales, the questionnaires, and an analgesic consumption record. In 18 of the 43 subjects a standardized preliminary dental extraction procedure was used as a control. Subsequent to the random allocation of an initial arch wire in 43 patients, 22 of them underwent a second arch wire in the opposing arch, the wire again being determined by random allocation. It was found that the prevalence, intensity, and duration of pain after the insertion of the two types of wire was similar but much greater than in the postextraction control phase. The pain score peaked on the morning after the placement of the arch wire, lasting typically for 5 to 6 days. The pain and discomfort experienced after the insertion of the second arch wire was similar to that of the first, no conditioning response being evident. Overall a diurnal variation was found with a tendency to an increase in pain in the evenings and nights, although this did not greatly affect sleep. The pain response was found to be highly and consistently subjective, not related to the dental arch, crowding, sex, or social class; however, a statistically significant association was found between the age and the pain experienced. PMID- 1456223 TI - Insurance essentials for the orthodontic practice. PMID- 1456224 TI - Directory: AAO officers and organizations. PMID- 1456225 TI - Joseph A. Gryson receives PCSO award of merit. PMID- 1456226 TI - Ronald Gross receives Devlin award. PMID- 1456227 TI - AAOF Endowment fund. PMID- 1456228 TI - (Up)righting misconceptions concerning the SPEED bracket system. PMID- 1456229 TI - Rigid internal fixation and the effects on the temporomandibular joint and masticatory system: a prospective study. AB - A prospective study of 22 patients who underwent a bilateral sagittal osteotomy to advance the mandible and subsequent rigid internal fixation, were examined for signs and symptoms of temporomandibular joint (TMJ) pain and masticatory dysfunction. A modified Helkimo index was used to analyze the anamnestic, clinical, and occlusal data. In addition, 12 of the cases chosen at random were mounted on a semiadjustable (SAM2) articulator and analyzed with the mandibular position indicator (MPI) to determine the amount and the direction of condylar displacement postoperatively. Anamnestic dysfunction decreased because of a reported decrease in muscular pain, joint noise, headache frequency, and parafunctional habits postoperatively. Clinical dysfunction remained unchanged, with a decrease in muscular soreness but with an increased incidence of joint clicking of 7%. The increased incidence of temporomandibular joint pain postoperatively was 4%. Increase in clinical dysfunction was most often seen in women and older patients. Occlusal dysfunction decreased, with the majority of interferences remaining after surgery as a result of insufficient lingual crown torque of the maxillary buccal segments. Occlusion is thought to have played only a minor role in temporomandibular joint and masticatory dysfunction. Reduction in range of motion was 10%, indicating the added benefit of early mobilization with rigid internal fixation procedures. The MPI study found the condyles inferiorly or inferoposteriorly displaced less than 1 mm from their preoperative position. These findings suggest that rigid internal fixation had no adverse effects on the temporomandibular and masticatory system. The variable responses and results can be attributed, at least in part, to the heterogenous population of patients studied and the variations in surgical techniques employed. PMID- 1456230 TI - Vertical changes in high-angle Class II, division 1 patients treated with cervical or occipital pull headgear. AB - Before, after, and 2 years after treatment serial radiographs of two samples of patients with high mandibular plane angle Class II, Division 1 nonextraction who were treated were evaluated retrospectively. One sample comprised patients treated with cervical headgear (CHG), and the other was treated with occipital headgear (OPHG). No significant differences were found when mandibular plane angle or facial height changes, anterior or posterior, were compared. Regarding vertical changes, only maxillary molar height, relative to both sella-nasion and palatal plane, and occlusal plane angle changes were significantly different when cervical and occipital-pull headgear were compared. In both groups of patients, responses to treatment were highly variable and only subtle vertical differences were apparent between mean changes in the cervical and occipital-pull samples. PMID- 1456231 TI - Mandibular displacement in Angle Class II, division 2 malocclusion. AB - The effect of the treatment of Angle Class II, Division 2 malocclusion was studied in 22 children by x-ray cephalometry and by recording the relation between the retruded and the intercuspal mandibular positions. The treatment was performed in three phases. In the first phase the upper incisors were proclined, and the deep bite was corrected with an upper removable plate. In the second phase the distal occlusion was corrected with an activator. The result was retained in the third phase with a second activator designed for retention. The relation between the retruded (RCP) and the intercuspal (ICP) mandibular positions was recorded with wax bites and dental casts mounted in a modified gnathothesiometer. The anteroposterior distance between RCP and ICP was large before the start of the treatment. The distance was unchanged after proclination of the upper incisors and correction of the deep bite but decreased after correction of the distal occlusion and increased again somewhat during the retention phase. The proclination of the upper incisors and the correction of the deep bite (phase one of the treatment) did not result in mandibular anterior positioning. This fact and the results of the recordings of the relation between RCP and ICP were interpreted as evidence that the mandible is not posteriorly displaced in Class II, Division 2 malocclusion. PMID- 1456232 TI - A study of reference lines for mandibular plane angles. AB - Four mandibular plane angles, MP-sella nasion, MP-Frankfort horizontal, MP articulare nasion, and MP-gnathion occiput, were compared. Highly significant correlations were found among all four. The relation of an extension of the mandibular plane to the posterior inferior outline of the cranium was found to provide a valid indication of mandibular plane angle. Articulare nasion was found to be the reference line most likely to provide a true indication of the mandibular inclination rather than a reflection of a variation in the reference line itself. PMID- 1456233 TI - Salivary clearance of sugar before and after insertion of fixed orthodontic appliances. AB - This study was conducted for the purpose of establishing the possible influence of orthodontic therapy with fixed appliances on salivary clearance of sugar. Fifteen consecutive patients between the ages 12 and 17 years took part in the investigation. Unstimulated salivary flow rate, residual volume of saliva in the mouth after swallowing (RESID), and salivary clearance of sugar was determined on two occasions, before treatment commenced and after a minimum of 3 weeks of appliance wear. Analysis of the data showed that both RESID and salivary flow rate exhibited significantly increased levels during orthodontic therapy. The insertion of fixed appliances did not seem to have any effect on the rate of salivary clearance of sugar. It was assumed that this finding could be a consequence of the combined effects of the changes in salivary flow rate and RESID. PMID- 1456234 TI - Apparatus criticus: methods used to evaluate growth modification in Class II malocclusion. PMID- 1456235 TI - The orthodontic management of congenitally absent maxillary lateral incisors and second premolars: a case report. AB - The orthodontic management of congenitally missing maxillary lateral incisors and second premolars is the subject of this case report. The primary orthodontic consideration was the maintenance of facial esthetics in a 12-year-old boy while consolidating, aligning, and coordinating the dental arches. The maxillary canines were orthodontically positioned in the lateral incisor spaces. The maxillary posterior teeth, including the deciduous second molars, were protracted to esthetic positions where they could function without interferences. The stability of the occlusion depends on the longevity of the maxillary deciduous second molar roots, which did not resorb during active tooth movement. PMID- 1456236 TI - Edward H. Angle versus Calvin S. Case: extraction versus nonextraction. Historical revisionism. Part II. PMID- 1456237 TI - Direct bonding metallic brackets: where are they heading? PMID- 1456238 TI - Practice and communications systems: a word processor based communications system. AB - The majority of computerized systems currently available for the orthodontic office have been designed for and aimed at those offices that have a volume practice and frequently have multiple practitioners. The stand-alone practitioner and the small office have been grossly ignored. Systems designed for large practices are frequently too complex, too involved in business administration, and too costly for the small office to use effectively. This article describes how an office communications system can be assembled by using commercially available programs. For background information and definition of terms used in this article, I suggest referring to "An Introduction to the Computerization of the Orthodontic Practice," in the Oct. issue of this Journal. PMID- 1456239 TI - The patient's records and the defense of dental malpractice claims. PMID- 1456240 TI - Directory: AAO officers and organizations. PMID- 1456242 TI - Retained umbilical stump: clinical approaches and separation anxiety. PMID- 1456241 TI - Toxic effects of methylene blue on the fetus. PMID- 1456243 TI - A life-threatening complication of percutaneous central venous catheters in neonates. PMID- 1456244 TI - Fatalities associated with misinterpretation of bloody cerebrospinal fluid in the 'shaken baby syndrome'. PMID- 1456245 TI - Pseudotumor cerebri in a boy with systemic lupus erythematosus. PMID- 1456246 TI - Acute scrotal involvement in children with familial Mediterranean fever. PMID- 1456247 TI - Safe and effective discipline. PMID- 1456248 TI - Laboratory evaluation of jaundice in newborns: corrections. PMID- 1456249 TI - Parenteral nutrition complications. PMID- 1456250 TI - Lacerations involving glass revisited. PMID- 1456251 TI - Rumination on the history of recognition of dehydration. PMID- 1456252 TI - Passive euthanasia for hypoplastic left heart syndrome. PMID- 1456253 TI - Medical decisions concerning the end of life in children in The Netherlands. PMID- 1456254 TI - How good a food for humans is cow's milk? From hyperbole up to hyperbole down. PMID- 1456255 TI - Pediatric euthanasia. AB - Pediatric euthanasia is currently practiced in the Netherlands on newborns, infants, children, and adolescents, although exact numbers are not known. Euthanasia in the Netherlands is generally assumed to be active and voluntary, but some cases of pediatric euthanasia would have to be characterized as nonvoluntary. Much of the motivation behind the euthanasia movement and the performance of pediatric euthanasia in the Netherlands is a genuine, compassionate desire to alleviate pain and suffering. In this study, we review the Dutch experience, with particular attention to the current practice of euthanasia on newborns, infants, children, and adolescents. We discuss pediatric euthanasia from an ethical point of view. We assert that more effective pain control, better symptom management, and psychosocial support of the dying and their families would alleviate the perception of suffering, and reduce the perceived need to resort to euthanasia. PMID- 1456256 TI - Surgical management of congenital heart disease in the 1990s. AB - OBJECTIVE: To provide a broad overview of recent trends in surgical management of congenital heart disease. DESIGN: Review of recent literature. SETTING: Major centers for surgical management of congenital heart disease. SELECTION PROCEDURES: Analysis of important recent clinical publications. INTERVENTIONS: None. RESULTS AND CONCLUSIONS: Definitive, corrective surgery was previously reserved for children beyond infancy. Recognition of the complications associated with palliative operations as well as the realization that neonates and infants did not fare worse than older children during open heart surgery provided the impetus for primary corrective surgery at an earlier age. Advances in our understanding of perioperative care, improved diagnostic capability, and increasing experience with corrective surgery in association with several different congenital heart lesions has resulted in an established therapeutic approach to surgical management of congenital heart disease in neonates and infants. PMID- 1456257 TI - Spontaneous chylothorax in Noonan syndrome. Treatment with prednisone. AB - OBJECTIVE: To describe a case of spontaneous chylothorax in a child with Noonan syndrome successfully treated with prednisone. DESIGN: Case report. SETTING: A pediatric cardiology referral center for the Rocky Mountain region. PATIENT: An 18-month-old girl with Noonan's syndrome, pulmonary stenosis, and hypertrophic cardiomyopathy who presented with spontaneous chylothorax. INTERVENTIONS: The child's chylothorax did not respond to thoracic duct ligation, tetracycline pleurodesis, and pleurectomy during a 2-month period. A low-fat diet was helpful but did not eliminate the problem. Prednisone was started orally at 1 mg/kg per dose twice daily and slowly tapered during 3 months. The chylothorax did not recur during 8 months of follow-up. CONCLUSIONS: Prednisone may be useful in the treatment of chylothorax in Noonan syndrome. A controlled clinical trial would be helpful but would be difficult in such a rare complication of an uncommon syndrome. PMID- 1456258 TI - Diabetic ketoacidosis in cystic fibrosis. AB - OBJECTIVE: To differentiate the insulin-dependent glucose intolerance associated with cystic fibrosis from type I diabetes mellitus in patients with cystic fibrosis. DESIGN: Patient report. SETTING: Tertiary care referral center. PARTICIPANT: An 11-year-old boy with cystic fibrosis who developed diabetic ketoacidosis. MEASUREMENT/MAIN RESULT: Biochemical, immunologic, and molecular techniques were used to support the sporadic association of type I diabetes mellitus in a patient with cystic fibrosis. Cystic fibrosis was confirmed by sweat test and further supported by the demonstration of a heterozygous deletion of the F508 locus. Evidence for the diagnosis of type I diabetes mellitus was developed from the clinical presentation of diabetic ketoacidosis with hyperglycemia, ketonemia, and ketonuria. Immunologic evidence included the demonstration of anti-insulin antibodies. The demonstration of homozygous absence of aspartic acid at position 57 of the HLA DQ-beta chain placed this child at high risk of type I diabetes mellitus. CONCLUSION: The clinical presentation and the presence of immunologic and genetic markers characteristic of type I diabetes mellitus supports the concordance of cystic fibrosis and type I diabetes mellitus in this patient. PMID- 1456260 TI - Helmets! All the pros wear them. AB - OBJECTIVE: To assess the outcome of a multidisciplinary community campaign to increase helmet use and determine the success of a school education and helmet distribution program. DESIGN: Survey research. SETTING: Large metropolitan area and two elementary schools. PARTICIPANTS: Five hundred representative families in a metropolitan area and students enrolled in two elementary schools. INTERVENTIONS: A 1-year-long regional media campaign and a helmet distribution program in one elementary school after 4 weeks of safety instruction. RESULTS: Evaluation of the community component 1 year after initiation of the campaign revealed a 23% awareness of the promotion. Factors associated with wearing a helmet in the community included higher income levels, higher level of education, and male sex. The school component survey revealed that 73% of the children in school A reported helmet use vs 23% in school B. This multifaceted approach to affect helmet use demonstrated variable success in our community. CONCLUSION: This campaign effort achieved its greatest success in promoting community awareness of the importance of helmet use. However, further studies need to be performed to determine the success of the school education and helmet distribution program. PMID- 1456259 TI - An unusual presentation of medium-chain acyl coenzyme A dehydrogenase deficiency. AB - OBJECTIVE: To report an atypical presentation of medium-chain acyl Coenzyme A dehydrogenase deficiency in a 13-year-old girl with hyperammonemic encephalopathy and orotic aciduria meeting the accepted criteria for diagnosis of a female heterozygous for ornithine transcarbamylase deficiency. DESIGN: Case report and definitive biochemical testing. SETTING: Children's hospital and university laboratory. PARTICIPANT: One teenager. INTERVENTIONS: Diagnosis and treatment with carnitine. MEASUREMENTS/MAIN RESULTS: Assay ornithine transcarbamylase deficiency had normal results. The diagnosis was confirmed by DNA analysis, which revealed homozygosity for prevalent mutation (the adenine to guanine transition at position 985). CONCLUSIONS: Patients with a clinical diagnosis of Reye's syndrome have, in general, an inborn error of metabolism. Medium-chain acyl Coenzyme A dehydrogenase deficiency and other disorders of fatty acid oxidation may present long after infancy. They may mimic the presentation of defects in the urea cycle. PMID- 1456261 TI - Radiological case of the month. Subperiosteal orbital abscess and ethmoid sinusitis. PMID- 1456262 TI - Picture of the month. Mastocytosis. PMID- 1456263 TI - Pathological case of the month. Spinal chordoma. PMID- 1456265 TI - Cranial computed tomographic scans have little impact on management of bacterial meningitis. AB - OBJECTIVE: To assess which clinical features predict an increased likelihood of an abnormal computed tomographic (CT) scan and how frequently CT influences management of bacterial meningitis. DESIGN: Retrospective patient series. SETTING: University-affiliated hospitals in Dallas, Tex. PATIENTS: Three hundred thirty-seven children with bacterial meningitis, of whom 107 (32%) had undergone CT scans. RESULTS: One or more abnormalities were found in 52% of the initial scans. The most frequent indication for CT at our institution was persistent or secondary fever, and in 56% of these children, subdural effusion or empyema was noted. However, findings on CT rarely predicted a need for intervention. In contrast, children with focal seizures or focal neurologic signs were more likely to have brain parenchymal changes. Scans in 19 patients (12%) prompted surgical intervention, most commonly drainage of a subdural collection. The conditions of only nine children (8.4% of those who had undergone CT scans) improved following intervention that was initiated because of findings on CT. CONCLUSIONS: Although CT scans are frequently abnormal in children with meningitis, CT seldom reveals findings that require specific intervention. PMID- 1456264 TI - Cognitive assessment of human immunodeficiency virus-exposed children. AB - OBJECTIVE: To determine (1) the level of impairment in cognitive and motor functioning in human immunodeficiency virus (HIV)-exposed and HIV-infected preschool and school-age children; (2) cognitive strengths and weaknesses that characterize HIV-infected children; and (3) potential contributions of serostatus, neurologic impairment, and prenatal drug-exposure to cognitive functioning. DESIGN: Cross-sectional, single-blind study. SETTING: Pediatric neurology clinic at a large metropolitan hospital in New York, NY. PARTICIPANTS: Forty-one HIV-infected and eight seroreverter school-age children. INTERVENTIONS: The McCarthy Scales of Children's Abilities were administered to all children, as was the Neurologic Examination for Children. MEASUREMENTS/MAIN RESULTS: The obtained mean of the sample on the McCarthy Scales' General Cognitive Index was in the Borderline range, with 44% of the subjects scoring in the Mentally Retarded range. The most severe cognitive deficits were found on the Quantitative, Verbal, and Memory scales (Borderline range). Children infected with HIV with neurologic impairment performed significantly worse than did seroverters and neurologically normal HIV-infected children. There were no significant differences in cognitive functioning due to gender, ethnicity, and prenatal drug exposure. CONCLUSIONS: Cognitive deficits were detected in HIV infected and seroreverted children. The presence of neurologic dysfunction in HIV infected children markedly intensified these deficits. PMID- 1456266 TI - Fluoride supplementation. A survey of pediatricians and pediatric dentists. AB - OBJECTIVE: To determine the protocol and use of prescriptions of fluoride supplementation by primary care pediatricians and pediatric dentists in the Houston (Tex) area. DESIGN: Survey mailed to all primary care pediatricians and pediatric dentists listed in the Yellow Pages of the Greater Houston telephone directory. PARTICIPANTS: 153 pediatricians and 47 pediatric dentists. MAIN RESULTS: Ninety-six percent of the participants prescribed fluoride supplements. Fifty-one percent of the pediatricians and 61% of the dentists considered that the fluoride content of the water was important. Seventy percent of the pediatricians and 30% of the dentists discontinued the use of supplements by age 7 to 10 years. CONCLUSIONS: Pediatricians and pediatric dentists should consider the need for water analysis prior to supplementation and should continue the use of fluoride supplements until 16 years of age. PMID- 1456267 TI - The Society for Epidemiologic Research (SER) and the future of epidemiology. PMID- 1456268 TI - Is acute lymphoblastic leukemia in children virus-related? AB - The sharp peak in incidence of acute lymphoblastic leukemia at ages 2 and 3 years strongly suggests the effect of an agent, whether viral or not, to which either exposure occurs only in the earliest months of life or to which immunity develops very rapidly. Suspected clusters of childhood leukemia in the neighborhoods of two British nuclear reprocessing facilities led Leo Kinlen to postulate that large-scale immigration into areas that had previously been remote and isolated offers opportunities for spread of viral infections to which most urban populations become immune at a very early age: leukemia may be a rare manifestation of infection by one or more of such viruses. He and his group have presented evidence in support of this hypothesis. Lack of increase in childhood leukemia in the contexts of the massive evacuation of mothers and children from British cities during the Second World War, and of the considerable immigration into previously isolated islands of Greece during the last several decades, indicates that some large movements of children have occurred without providing the circumstances postulated by Kinlen. The marked inverse association of leukemia risk with birth order, noted almost 30 years ago, remains unexplained and deserves to be recalled when considering the possibility of viral involvement in the etiology of acute lymphoblastic leukemia of children. PMID- 1456269 TI - Risk factors predicting the incidence of second primary breast cancer among women diagnosed with a first primary breast cancer. AB - This study examined risk factors for development of a contralateral breast cancer among 4,660 US women diagnosed with a first primary breast cancer between 1980 and 1982. The authors believe it to be the first prospective cohort study on this topic that has employed direct patient interviews. All subjects were interviewed within 6 months of the diagnosis of their initial tumor as part of the multi center, population-based, case-control Cancer and Steroid Hormone Study, and they were followed until the end of 1986 through the Surveillance, Epidemiology, and End Results program. Exclusive of those diagnosed during the initial 6 months after diagnosis of a first primary, 136 second primary breast cancers were identified. Proportional hazards models were used to assess the independent effects of multiple predictors. Specific risk factors evaluated included: age at diagnosis of first primary, exposure to exogenous hormones, menstrual and reproductive histories, tumor characteristics, demographic variables, and treatment modalities. The age-specific incidence rates of second primary breast cancer were higher in all age categories than are the incidence rates of breast cancer in the general population, yet the age at diagnosis of first primary breast cancer was not an important predictor of contralateral breast cancer. The risk of contralateral breast cancer was increased among cohort members who reported a personal history of benign breast biopsy (multivariable-adjusted rate ratio (RR) = 1.69, 95% confidence interval (CI) 1.13-2.53) and in those with an initial tumor that was classified as lobular carcinoma (multivariable-adjusted RR = 1.96, 95% CI 1.17-3.27). Treatment with chemotherapy for the first primary was associated with a lower risk of development of a second breast cancer (multivariable-adjusted RR = 0.56, 95% CI 0.33-0.96), while radiation therapy had little effect on the risk (multivariable-adjusted RR = 1.19, 95% CI 0.78-1.80). PMID- 1456270 TI - The genetic epidemiology of second primary breast cancer. AB - It is well established that women with a family history of breast cancer run a higher risk of breast cancer than do women without a family history. The evidence, however, is less clear regarding a possible association between a family history of breast cancer and risk of second primaries. The purpose of this prospective study was to estimate the risk for second primary breast cancer associated with having a family history of breast, endometrial, and ovarian cancers. A cohort of 4,660 women with a first primary breast cancer diagnosed between 1980 and 1982 were interviewed as part of the Cancer and Steroid Hormone Study, a multi-center population-based case-control study, and followed through eight Surveillance, Epidemiology, and End Results (SEER) program registries for 4 to 6 years. Of these women, 136 developed a second primary breast cancer in the contralateral breast at least 6 months after diagnosis of the first primary. Cox proportional hazards modeling techniques were used to model the time to onset of second primary breast cancer while adjusting for multiple predictors. The risk of contralateral breast cancer was elevated among cohort members who reported a history of breast cancer in a first-degree relative (multivariable-adjusted rate ratio (RR) = 1.91, 95% confidence interval (CI) = 1.22-2.99). Early age at onset (< 46 years) in the relative further increased the risk of developing contralateral breast cancer (sister: multivariable-adjusted RR = 3.36, 95% CI 1.62-6.98; mother: multivariable-adjusted RR = 2.35, 95% CI 1.02-5.43). Bilateral breast cancer in mothers was also associated with more than a two and a half-fold increase in risk (multivariable-adjusted RR = 2.55, 95% CI 1.02-6.35). The association between family history of breast cancer and risk of contralateral breast cancer did not vary substantially according to age at onset of the first primary breast cancer. The age-adjusted rate ratio for development of a second primary breast cancer among women with a first-degree relative with endometrial cancer was 2.13 (95% CI 1.04-4.35), while the corresponding rate ratio among women with a family history of ovarian cancer was 1.69 (95% CI 0.42-6.83). There was little evidence that age at onset among the relatives with endometrial or ovarian cancer affected the risk. Some of these findings have not been previously reported and need replication in future studies. PMID- 1456271 TI - Localization and characterization of calcitonin gene-related peptide mRNA in rat heart. AB - Calcitonin gene-related peptide (CGRP), a product of the calcitonin/CGRP gene, is a potent vasodilating neuropeptide widely distributed throughout the cardiovascular system, particularly in the heart. Immunocytochemical studies have demonstrated CGRP-containing neurofibrils in the myocardium and in the periadventitia of coronary blood vessels. Based on these studies, it has been assumed that all of the CGRP peptide in the heart is synthesized in neurons whose cell bodies are located outside of the heart. Using Northern blot analysis and a ribonuclease protection assay, we observed in the rat heart low levels of a CGRP like mRNA species that appeared to be identical to authentic CGRP mRNA produced in the brain and dorsal root ganglia. The ventricles contained somewhat more CGRP mRNA than did the atria. Also, whereas the dorsal root ganglia synthesized both alpha- and beta-CGRP mRNA, only the alpha-CGRP mRNA was detected in the heart. The presence of CGRP mRNA in the heart suggests that the CGRP gene is transcriptionally active in a subpopulation of heart cells, possibly neuronal, which have the potential to synthesize and secrete this neuropeptide. Given the potent coronary vasodilatory and positive chronotropic and inotropic effects of CGRP, the localized synthesis of CGRP in the heart may play a role in modulating cardiovascular function. PMID- 1456272 TI - Small caliber catheter drainage for spontaneous pneumothorax. AB - Excellent results have been reported after small caliber catheters were used for iatrogenic pneumothoraces. However, the value of using such catheters for spontaneous pneumothoraces is not clear. The purpose of this study, therefore, is to examine the efficacy of small caliber catheters in managing spontaneous pneumothoraces. Seventy six episodes of spontaneous pneumothorax were treated using a small caliber catheter (No. 5.5 or 7.0 French) connected to a Heimlich valve. All catheters were inserted by physicians. The treatment was considered successful when there was no air leakage and little or no residual pneumothorax. Before the lungs were fully expanded, four patients had died and one had refused to comply with further treatment. The remaining 71 episodes of pneumothoraces were evaluated for efficacy. The treatment was successful in 60 patients (84.5%) and ineffective in the remaining 11. The conventional large caliber tube was inserted in 10 of the 11 failures, but they were successful in only six. No major complications resulting from catheter insertion occurred, and no catheters became occluded. The catheter was easy to insert, and the scar that remained after removal of the catheter was very small. Not only are small caliber catheters effective for managing spontaneous pneumothoraces, they are the initial treatment of choice. PMID- 1456273 TI - Institutional Review Board (IRB) review lacks impact on the readability of consent forms for research. AB - Consent forms in research are a source of current and retrospective information for the subject, a "prompt" for the person who is obtaining consent, and a documentation of the "informed" consent process and its adequacy. Occasionally, these forms may be administered by inexperienced trainees or ancillary personnel, and thus stand virtually alone. Therefore, the forms must be inherently comprehensible to the subjects. To test whether this is the case, 65 new applications were randomly selected from 13 consecutive IRB agendas, and their consent documents were computer-analyzed (Flesch/Fry scoring) after correction for expected confounding features, such as lists, tables, and polysyllabic proper names and jargon. Mean U.S. school grade for 70% comprehension (Fry score) was 15.03 +/- 0.19 (standard error of the mean), implying readability by 37.4 +/- 1% of the U.S. adult population. In contrast, a consecutive sampling of 21 Ann Landers columns yielded a mean Fry score of 7.67 +/- 0.5 (p < 0.01; readable by 75 +/- 3%). Fifteen Reader's Digest articles yielded a mean Fry score of 9.95 +/- 0.65 (p < 0.01; readable by 59.1 +/- 3%), and 15 "Talk of the Town" columns from The New Yorker averaged a grade level of 13.3 +/- 0.83; p < 0.01; readable by 42.7% +/- 4.8%). No document was improved by more than one grade level by the IRB review process, and most were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456274 TI - Case report: sustained-release verapamil overdose causing stroke: an unusual complication. AB - A 47-year-old woman ingested 7.2 gm of sustained-release verapamil. She developed hypotension, idioventricular rhythm, mild acidosis, mild hyperglycemia, and aspiration pneumonia that required antibiotics and mechanical ventilatory support. In addition, she had a stroke, which resulted from left cerebral hemispheric damage, an unusual complication. Stroke is reported only once in the literature. Special problems related to slow release medication and the need to be aware of them are discussed. PMID- 1456275 TI - Case report: diagnosis of thyroid cancer by bone marrow biopsy in a patient with lymphoma and goiter. AB - Metastatic follicular thyroid carcinoma was diagnosed by bone marrow biopsy performed during the staging evaluation in a patient with large-cell lymphoma and diffuse goiter who showed lung and bone lesions upon radiologic examination. After thyroidectomy, both sites concentrated radioactive iodine, confirming their thyroid origin and allowing for the appropriate treatment. PMID- 1456277 TI - Ondansetron: pharmacology of a specific 5HT3-receptor antagonist. PMID- 1456276 TI - Structure and applications of intermolecular DNA triplexes. AB - Current DNA binding drugs are not sequence specific. Triplex-forming oligonucleotides will bind targeted duplex DNA sites in a sequence-specific manner. A new class of DNA binding molecules based on triple-helical DNA formation promises a sequence-specific method of targeting discrete regions of DNA. DNA modifying molecules linked to third strands have been shown to modify only regions of DNA to which they were targeted. Current research will increase the understanding of triplex DNA structure and will lead to improved DNA binding drugs. PMID- 1456278 TI - Infections of the central nervous system. AB - Infections of the central nervous system are common, serious medical conditions. One hundred consecutive adult cases with purulent meningitis of known etiology encountered by the Medical Service at Parkland Memorial Hospital were reviewed. Streptococcus pneumoniae was the most common pathogen (56 cases), followed by Neisseria meningitidis (16 cases) and Listeria monocytogenes (seven cases). Hemophilus influenzae, Staphylococcus aureus, and streptococci each accounted for five cases. An additional 15 patients had purulent meningitis with a pathogen being isolated. Twenty five purulent meningitis cases of known etiology after trauma or neurosurgery were reviewed. Staphylococcus aureus (five cases), Staphylococcus epidermidis (four cases), and gram negative bacilli (14 cases) were the most common pathogens. Review of intracranial suppurative infections demonstrated advances in microbiology, antibiotic therapy, and imaging, leading to improvements in therapy. Subdural empyema continues to be a difficult diagnosis to make and apparently is related to the anatomic pathology of the infectious process. To illustrate salient features about granulomatous meningitis and encephalitis, cases of tuberculous meningitis, herpes simplex encephalitis, St. Louis encephalitis, and encephalitis of undetermined etiology are presented and discussed. PMID- 1456279 TI - Report of another family with Simpson-Golabi-Behmel syndrome and a review of the literature. AB - Simpson-Golabi-Behmel Syndrome (SGBS), an X-linked encephalo-tropho-schisis syndrome described in fewer than a dozen families, is characterized by pre- and postnatal overgrowth, "coarse" face, minor facial anomalies and, in more severe cases, multiple congenital anomalies and mental retardation. We report on 2 brothers with overgrowth, macrocephaly, polydactyly, supernumerary nipples, and characteristic facial appearance. In addition, the propositus also had pulmonic stenosis and a cleft palate. The findings present in our patients are compared to those in the original patients and to those in patients described more recently. Despite the fact that our patients have most of the minor and several of the more severe malformations, they are not mentally retarded. PMID- 1456280 TI - Further delineation of the Simpson-Golabi-Behmel (SGB) syndrome. AB - The Simpson-Golabi-Behmel syndrome is an X-linked condition characterized by pre- and postnatal overgrowth, "coarse" face, postaxial polydactyly, midline defects, and psychomotor development ranging from normal to mildly retarded. We report on an additional sporadic patient with novel manifestations, contributing to a more thorough delineation of this syndrome. PMID- 1456281 TI - Proximal 7q interstitial deletion in a severely mentally retarded and mildly abnormal infant. AB - We describe a boy with an interstitial deletion of 7q [46,XY,del(7)(pter- >q11.21::q11.23-->qter)] and severe mental retardation, bilateral inguinal hernias, plagiocephaly, and mildly abnormal facial appearance. This is the 21st case report involving a proximal 7q deletion, but the first report of this specific deletion in the absence of Zellweger syndrome. Specific genotype phenotype correlations are still not possible for this region of chromosome 7. PMID- 1456282 TI - Mucopolysaccharidosis VII as cause of fetal hydrops in early pregnancy. AB - We report on fetal hydrops presenting at 18 weeks of gestation and diagnosed as beta-glucuronidase deficiency. The parents were first cousins and there were 2 previous similar fetal deaths. beta-Glucuronidase was absent in cultured fetal fibroblasts and lymphoblasts but was normal in the tested relatives. The activities of other lysosomal enzymes were normal. PMID- 1456283 TI - Mucopolysaccharidosis type VII (beta-glucuronidase deficiency): a chronic variant with an oligosymptomatic severe skeletal dysplasia. AB - We report on a 20-year-old male with a beta-glucuronidase (GUSB) deficiency mucopolysaccharidosis. He had pectus carinatum, gross thoracic kyphoscoliosis, and hip dysplasia, a picture which became conspicuous after age 4 years. Hepatosplenomegaly, herniae, corneal clouding, and neurological abnormalities were absent. Although he had Alder-type granulations in his polymorphonuclear leukocytes, the urine did not contain a significant excess of mucopolysaccharides. Electron microscopic examination of skin and gingival biopsies, leukocytes, and cultured skin fibroblasts showed numerous single membrane-limited vacuoles either empty or filled with fibrillogranular material; this last tissue did not contain metachromatic granules. Radiographs demonstrated a distinct spondyloepiphyseal dysplasia in which the most striking changes were confined to the thoracic spine (flattening and collapse in T7, T8 and T10 vertebral bodies) and to the femoral capital epiphyses (irregularities and fragmentation). The activity of GUSB in the patient's serum, leukocytes, and fibroblasts was severely decreased; the GUSB activity in the serum and leukocytes from the parents and 2 asymptomatic sibs was subnormal. Immunoblot analysis showed very low levels of cross-reactive material towards anti-GUSB antiserum in the patient's leukocyte and fibroblast extracts. This patient was more severely affected in his skeleton than other described patients with an oligosymptomatic chronic form. This case broadens the clinical and biochemical picture associated with GUSB deficiency and may represent a new variant of the disease. PMID- 1456284 TI - Autosomal recessive cleft lip/palate, ectodermal dysplasia, and minor acral anomalies: report of a Brazilian family. AB - We report on a Brazilian woman, born to consanguineous (first cousin) parents (F = 1/16) and presenting cleft lip/palate, ectodermal dysplasia, interdigital webbing, and other malformations. Parental consanguinity and possible recurrence in sibs suggest autosomal recessive inheritance. The nosologic aspects with the Martinez syndrome and with the Zlotogora-Ogur syndrome are discussed. PMID- 1456285 TI - Constitutional translocation t(4;22) (q12;q12.2) associated with neurofibromatosis type 2. AB - We report on a female patient with bilateral acoustic neurinomas and other tumors in the central nervous system (neurofibromatosis type 2: NF2) and the constitutional translocation, t(4;22) (q12;q12.2). The precise identification of the translocation breakpoint (q12.2) on chromosome 22 implies the refined localization of a gene responsible for NF2, and would provide a clue to its molecular characterization and to the isolation of the gene. Chromosomes of a paraspinal neurinoma from the patient were also analyzed, and the same karyotype as seen in cultured peripheral lymphocytes was found. The patient's father was also a carrier of the translocation, but he had no clinical symptoms of NF2, nor did other relatives. Several explanations are offered for the different expression of the translocation between the patient and her father. PMID- 1456286 TI - Experimental fetal alcohol syndrome: proposed pathogenic basis for a variety of associated facial and brain anomalies. AB - Acute teratogenic exposure of C57Bl/6J mouse embryos to ethanol in vivo results, within 12 hours of initial insult, in excessive cell death in selected cell populations. The patterns of excessive cell death observed following exposure of gestational day 8 embryos (late presomite--approximately 5 somite pair stages) vary somewhat temporospatially, but primarily involve the cell populations at the rim of the anterior neural plate. The cell death patterns appear to be pathogenically correlated with subsequently observed malformations including exencephaly (anencephaly), arhinencephaly, pituitary dysplasia, bilateral or unilateral cleft lip, maxillary hypoplasia, and median facial deficiencies and clefts. The association of these brain and facial malformations in this model, and perhaps in humans, may be accounted for by early insult to the selected cell populations identified in the current investigation. PMID- 1456287 TI - Long-term evaluation of a child with the branchio-oculo-facial syndrome. AB - We report on the 12-year development of a child with branchio-oculo-facial syndrome who was initially referred at age 5 months. Of note is his normal intelligence, regular class placement, hypernasal speech, and continued growth along the third centile. The importance of serial observations of patients with rare genetic disorders is emphasized. PMID- 1456288 TI - Twin studies in familial Mediterranean fever. AB - Familial Mediterranean fever (FMF) is a genetic disease characterized by recurrent short episodes of fever, accompanied by peritonitis, pleuritis, or arthritis. The disease is almost completely ethnically restricted to patients of Mediterranean descent--Sephardic Jews, Armenians, Anatolian Turks, and Arabs. Although many family studies have been performed, no twin study has been reported as yet. We studied 21 di- and monozygotic twin sets, identified among the 1,943 FMF patients in our registry. Full concordance was observed in all the 10 monozygotic twin sets. In the 11 dizygotic twins, concordance for FMF disease was found in only 3 pairs. Variability in the clinical manifestations and degree of severity have been noted within twins. These findings provide definitive evidence for the genetic cause of FMF. They also support the single gene autosomal recessive model, and provide support for the contention that the lower observed than expected incidence found in FMF is due to genetically affected but clinically undiagnosed patients. PMID- 1456289 TI - Familial Mediterranean fever: analysis of inheritance and current linkage data. AB - Familial Mediterranean fever (FMF) is a genetic disorder characterized by recurrent attacks of fever and inflammation of serosal surfaces. Unlike many mendelian disorders, the mode of transmission has been subject to some controversy as segregation analysis studies have always demonstrated fewer "observed" than "expected" affected individuals. Despite efforts to map the gene causing FMF, no definite linkage has been yet identified. This review analyses the epidemiologic and genetic characteristics in order to evaluate critically the inheritance of the disease and provide a perspective on the current biochemical and molecular genetic studies whose aim is to locate the gene for this disease. PMID- 1456290 TI - Natural history of mosaic trisomy 14 syndrome. AB - Trisomy 14 mosaicism produces a distinct phenotype. Among the 13 reported and 2 additional patients, the following findings were present in more than 90%: growth retardation (15/15), psychomotor retardation (10/10), broad nose (13/14), "dysplastic" and/or apparently low-set ears (15/15), micrognathia (15/15), short neck (11/12), congenital heart disease (14/15), and micropenis and cryptorchidism (6/6). Other frequent findings were prominent forehead (12/14), hypertelorism (8/13), narrow palpebral fissure (7/9), large mouth (10/14), cleft or highly arched palate (10/14), body asymmetry (8/12), and abnormal skin pigmentation (6/10). Sex ratio was 6M:9F. Four patients died before age 4 months, while at least 2 patients survived through teens. One boy died at age 3 years following cardiac surgery. One girl with tetralogy of Fallot showed a remarkable improvement in health after Blalock-Taussig procedure. Although the surviving patients showed moderate growth and mental retardation, the oldest surviving woman at 29 years demonstrates functional language and appropriate self help skills. PMID- 1456291 TI - Cutaneous scar at anterior hair line in mother and child with associated frontal bone defect in child. AB - A large frontal bone defect underlying a "V" shaped scar was noted in a newborn male whose mother had an identical "V" shaped scar at the same location in the anterior hairline. Both had hypertelorism and short palpebral fissures. The mother had no radiographic evidence of skull defect and neither mother nor child had other cutaneous or skeletal anomalies. Cranioplasty was performed on the child using the remaining frontal bones with an excellent cosmetic result. Biopsy performed at operation documented scar tissue extending through the dermis and underlain by thickened dura. Mother and child appear to have a variant form of aplasia cutis congenita, an autosomal dominant trait with wide variation in expression. PMID- 1456292 TI - Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (Tapazol) during pregnancy. AB - We report on 2 newborn infants with esophageal atresia and tracheoesophageal fistula (EA + TEF) born to hyperthyroid mothers receiving methimazole (Tapazol) before and during their entire pregnancies. Both mothers were euthyroid during gestation and developed hydramnios diagnosed during weeks 34 and 33 of gestation. Premature delivery (36.2 weeks of gestation) occurred in one case, and both newborn infants were small for date with palpable goiter; one of them had other associated malformations. Hypothyroidism was diagnosed by laboratory tests in both cases. Corrective surgery was undertaken, but both newborn infants developed septicemia and renal insufficiency and died in the first week of life. The EA + TEF and a normally placed enlarged thyroid gland were confirmed at necropsy. These cases represent a previously unreported example of the association of maternal ingestion of methimazole during pregnancy and EA + TEF. PMID- 1456293 TI - Caroline Crachami and the delineation of osteodysplastic primordial dwarfism type III, and autosomal recessive syndrome. PMID- 1456294 TI - Caroline Crachami, the Sicilian Fairy: a case of bird-headed dwarfism. AB - One of the most remarkable cases of extreme dwarfism on record is Caroline Crachami, the Sicilian Fairy. She was born in 1815, and was taken to London to be exhibited for money in 1824. Due to her proportional dwarfism, severe intrauterine growth retardation, and typical "bird-headed" profile, Caroline Crachami has by some been diagnosed as a case of the autosomal recessive Seckel syndrome. In this historical vignette, the Sicilian Fairy's life and death are presented in some detail using new material, and the problem of her correct diagnosis is discussed. PMID- 1456295 TI - 6p23 deletion mosaicism in a woman with recurrent abortions and idiopathic hypoprolactinemia. AB - A woman with a history of recurrent abortions, idiopathic hypoprolactinemia, and an apparent 6p partial deletion mosaicism is described. The breakpoint in the short arm of chromosome 6 was in the p23 region. This deletion could have been caused by a fragile site in 6p23. PMID- 1456296 TI - Hypoplasia of the corpus callosum and growth hormone deficiency in the XXXXY syndrome. AB - A 3-year-old Libyan boy with the XXXXY syndrome is described. MRI examination of the brain showed hypoplasia of the corpus callosum. He had growth retardation and endocrine studies demonstrated growth hormone (GH) deficiency. Dermatoglyphic pattern was different from previous reports. At histological examination of the undescended testes, Leydig cells were seen although they are usually not found in this variant of the Klinefelter syndrome. PMID- 1456297 TI - Child with manifestations of dermotrichic syndrome and ichthyosis follicularis alopecia-photophobia (IFAP) syndrome. AB - We report on a boy with short stature, mental retardation, seizures, follicular ichthyosis, generalized alopecia, hypohydrosis, enamel dysplasia, photophobia, congenital aganglionic megacolon, inguinal hernia, vertebral, renal and other anomalies, and a normal chromosome constitution. The clinical findings include all the features that dermotrichic and ichthyosis follicularis-alopecia photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia, recurrent respiratory infections, etc.), those that are present only in dermotrichic syndrome (nail anomalies, hypohydrosis, megacolon, vertebral defects, etc.) and additional ones (enamel dysplasia, renal anomalies, inguinal hernia, etc.). Two maternal uncles were referred as being affected by alopecia and ichthyosis suggesting X-linked recessive transmission. Various hypotheses concerning the relationship between the 2 syndromes and the present case are discussed. PMID- 1456298 TI - Tentative assignment of a locus for Rubinstein-Taybi syndrome to 16p13.3 by a de novo reciprocal translocation, t(7;16)(q34;p13.3). AB - During a systematic chromosomal survey of 7 unrelated patients with Rubinstein Taybi syndrome, an apparently balanced de novo reciprocal translocation, t(7;16)(q34;p13.3), was detected in an affected boy. The involvement of the region 16p13.3 coincides with the position of one of the breakpoints in another de novo reciprocal translocation associated with Rubinstein-Taybi syndrome, suggesting that a locus for this syndrome maps to 16p13.3. PMID- 1456299 TI - Omodysplasia. PMID- 1456300 TI - Deletion 9p syndrome and malignancy: acquired vs. constitutional aberrations? PMID- 1456301 TI - Human situs determination is probably controlled by several different genes. PMID- 1456302 TI - Alpha-thalassemia/mental retardation syndrome often confused with other disorders. PMID- 1456303 TI - Report of another child with sex reversal and cardiac, pulmonary, and diaphragm defects. PMID- 1456304 TI - Ectrodactyly with multiple congenital abnormalities. PMID- 1456306 TI - A $5 day. PMID- 1456305 TI - Deletion in one allele and a rare neutral DNA alteration in the other allele of the RB1 gene in a patient with bilateral retinoblastoma. PMID- 1456307 TI - Gifts we keep. PMID- 1456308 TI - Death anxiety: finding support in families. PMID- 1456309 TI - Antiarrhythmic drug risks. PMID- 1456310 TI - Euthanasia's dangers. PMID- 1456311 TI - The right to fire v. the public interest. PMID- 1456312 TI - Heart smart: a guide to cardiac tests. PMID- 1456313 TI - Dialogues with excellence. Seeing Joan through. PMID- 1456314 TI - What keeps oxygenation on track? PMID- 1456315 TI - Seasonal affective disorder: light makes right. PMID- 1456316 TI - Drug response: all bodies are not created equal. PMID- 1456317 TI - $100,000 AIDS payout is Boston's new norm. PMID- 1456318 TI - The path of least (staff) resistance. PMID- 1456319 TI - Exploring electronic support groups. PMID- 1456320 TI - An HIV-infected nurse must be reinstated. PMID- 1456321 TI - Occupation as vision. PMID- 1456322 TI - Ten milestone issues in AOTA history. AB - This paper identifies 10 professional questions that the author has labeled milestone issues in the history of the American Occupational Therapy Association. Subjects encompassed by these issues are medical control, certified occupational therapy assistants, licensure, proficiency testing, entry-level degrees, treatment media, maintenance of competency, whether occupational therapists serve patients or clients, professional autonomy, and the status of occupational therapy as a profession. Although this paper is primarily a factual record of events and discussions referenced in official publications, the reader will recognize the insertion of author commentary and opinion in several of the issues discussed. PMID- 1456323 TI - Use of adjunctive modalities in occupational therapy. AB - This article reminds us that as practice evolves, we must revisit and reaffirm the fundamental philosophy and precepts in which our profession is grounded. The face of practice is fluid. Its superficial appearance is molded by external forces and stresses. These include the changes in the needs of the persons we serve, the emergence of new and different treatment modalities, and the realities of the socioeconomic environment in which we work. Beneath the surface, however, are the basic structures that all of us hold in common. These are our philosophical beliefs that are articulated both in the professional literature and in the ethical principles that we espouse. PMID- 1456324 TI - Standards of practice for occupational therapy. PMID- 1456325 TI - Statement: occupational therapy services in work practice. AB - Occupational therapy practitioners focus on the individual's ability to participate in productive occupations throughout their life span. Through prevention, assessment, and intervention strategies, occupational therapy practitioners often collaborate with other members of the health care team and assist persons to optimize their ability to engage in purposeful occupation while facilitating a safe and successful entry into or return to work. PMID- 1456327 TI - Listing of educational programs in occupational therapy. PMID- 1456326 TI - Position paper: physical agent modalities. PMID- 1456328 TI - Final report: Intercommission Council completes advanced practice review. PMID- 1456329 TI - Graduate programs for occupational therapists. PMID- 1456330 TI - What makes a group heterogeneous? PMID- 1456331 TI - Inferences from secular trend analysis of hypertension control. PMID- 1456332 TI - The US decline in stroke mortality: what does ecological analysis tell us? AB - We review a study in this issue that concludes, from analyses of ecological associations, that the use of medication to lower high blood pressure has caused at most a small decline in US stroke mortality rates. Our analysis suggests that other possible sources of the decline may be population-wide falls in levels of blood pressure, cigarette smoking, and coronary heart disease mortality, as well as improved treatment of cardiac and respiratory sequelae of stroke. Although the ecological method is powerful for answering questions about medical interventions' population-wide effects on disease, it must be used with care. Of particular concern are variables with meanings that differ between the ecological and the individual levels, the number of ecological units available for analysis, the sample size within the ecological units, and the range of independent variables used in ecological regression. PMID- 1456333 TI - Antihypertensive treatment and US trends in stroke mortality, 1962 to 1980. AB - OBJECTIVES: This study examines the association between increases in antihypertensive pharmacotherapy and declines in stroke mortality among 96 US groups stratified by race, sex, age, metropolitan status, and region from 1962 to 1980. METHODS: Data on the prevalence of controlled hypertension and socioeconomic profiles were obtained from three successive national health surveys. Stroke mortality rates were calculated using data from the National Center for Health Statistics and the Bureau of the Census. The association between controlled hypertension trends and stroke mortality declines was assessed with weighted regression. RESULTS: Prior to 1972, there was no association between trends in controlled hypertension and stroke mortality declines (beta = 0.04, P = .69). After 1972, groups with larger increases in controlled hypertension experienced slower rates of decline in stroke mortality (beta = 0.16, P = .003). Faster rates of decline were modestly but consistently related to improvements in socioeconomic indicators only for the post-1972 period. CONCLUSIONS: These results do not support the hypothesis that increased antihypertensive pharmacotherapy has been the primary determinant of recent declines in stroke mortality. Additional studies should address the association between declining stroke mortality and trends in socioeconomic resources, dietary patterns, and cigarette smoking. PMID- 1456334 TI - Correlates of nonadherence to hypertension treatment in an inner-city minority population. AB - OBJECTIVE: Adherence to treatment is a key factor in achieving blood pressure control among hypertensives. We examined correlates of nonadherence to hypertension treatment in an inner-city minority population. METHODS: Subjects (n = 202) were interviewed as part of a case-control study of severe, uncontrolled hypertension conducted in two New York City hospitals in 1989-91. All subjects were African American or Hispanic. Self-reported nonadherence to drug treatment for hypertension was measured using a five-item scale, and the sample was dichotomized as more (n = 87) or less (n = 115) adherent. Multiple logistic regression analysis was used to adjust for demographic and other covariates. RESULTS: Nonadherence was associated with having blood pressure checked in an emergency room (adjusted odds ratio [OR] = 7.9; 95% confidence interval [CI] = 1.75, 35.77; P < .01), lack of a primary care physician (adjusted OR = 2.9; 95% CI = 1.37, 6.02; P < .01), current smoking (adjusted OR = 2.4; 95% CI = 1.10, 5.22; P = .03), and younger age (adjusted OR = 1.03, 95% CI = 1.00, 1.06; P = .03). CONCLUSIONS: Changing the locus of care for hypertension from emergency rooms to primary care physicians may improve adherence to hypertension treatment in minority populations. PMID- 1456335 TI - Obesity and cardiovascular disease risk factors in black and white girls: the NHLBI Growth and Health Study. AB - OBJECTIVES: Obesity may be a possible explanation for the higher cardiovascular disease mortality in Black women compared with White women. The National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) is designed to assess factors associated with the development of obesity in Black and White preadolescent girls and its effects on major cardiovascular-disease risk factors. METHODS: NGHS is a 5-year cohort study of 2379 girls, aged 9 through 10 years at entry. Anthropometry, blood pressure, and maturation staging are measured annually, and blood lipids biannually. Information on education, income, and family composition is also obtained from parents. RESULTS: At baseline, compared with White girls, Black girls were slightly older, biologically more mature, taller, heavier, and had higher Quetelet Indices, skinfolds, and blood pressures. Black girls had lower triglycerides and higher HDL cholesterol than White girls. Total cholesterol and LDL cholesterol were similar in the two groups. CONCLUSIONS: Baseline descriptive characteristics of the NGHS cohort showed that, in subjects aged 9 and 10 years, racial differences in obesity and blood pressure were already present. PMID- 1456336 TI - Correlates of obesity in young black and white women: the CARDIA Study. AB - OBJECTIVES: Although differences in obesity between Blacks and Whites are well documented in adult women, less information is available on potential correlates of these differences, especially in young adults. METHODS: The association between behavioral and demographic factors and body size was assessed in 2801 Black and White women aged 18 to 30 years. RESULTS: Black women had significantly higher age-adjusted mean body mass index and subscapular skinfold thickness than did White women. Obesity had different associations with age and education across racial groups. A positive relationship between age and obesity was seen in Black women but not in White women, whereas a negative association between education and body size was noted only in White women. Potential contributing factors to the increased prevalence of obesity in Black women include a more sedentary lifestyle, higher energy intake, earlier menarche, and earlier age at first childbirth. CONCLUSIONS: The difference in obesity across race could not be explained completely by these factors, since within virtually all strata, Black women had higher body mass indexes. Further investigation is needed to develop interventional strategies to prevent or reduce excess levels of obesity in Black women. PMID- 1456337 TI - HMO vs fee-for-service care of older persons with acute myocardial infarction. AB - OBJECTIVES: Health maintenance organizations (HMOs) continue to grow in number and in their enrollment of Medicare recipients. They are also increasingly viewed as organizational structures that might contribute to control of health care costs. Yet little is known about the quality of care that elderly HMO enrollees receive. METHODS: We compared patients from three HMOs to a fee-for-service (FFS) sample that was national in scope. Sickness at admission, the quality of process of care, and mortality were assessed for patients aged 65 years and older who had been hospitalized with a diagnosis of acute myocardial infarction. RESULTS: After adjustment for sickness at admission, there were no significant mortality differences between the HMO and FFS groups at either 30 (23.2% vs 23.5%) or 180 days (34.4% vs 34.5%) after admission. Compliance with process criteria was higher for the HMO group as a whole (P < .05). The HMOs had greater compliance with three of five scales measuring different aspects of care for patients with acute myocardial infarction. CONCLUSIONS: We conclude that older patients from our participating HMOs who were hospitalized for acute myocardial infarction received hospital care that was generally better in terms of process than that received by patients in a national FFS sample. PMID- 1456339 TI - The mortality of lead smelter workers: an update. AB - OBJECTIVES: Mortality studies of lead workers have shown excesses of nonmalignant renal disease and cerebrovascular disease. Animal studies and one human study have shown excess kidney cancer. We have updated a mortality study of male lead smelter workers (n = 1990). METHODS: An analysis was conducted using standard life table techniques. The updated analysis added 11 years of follow-up and 363 new deaths. RESULTS: The original study had found elevated but nonsignificant risks for kidney cancer, stroke, and nonmalignant renal disease, probably attributable to lead exposure. Deaths from accidents and nonmalignant respiratory disease were significantly elevated, but probably not as a result of lead exposure. In the updated study, no new deaths from nonmalignant renal disease occurred (9 observed, standardized mortality ratio = 1.21). Three more deaths from kidney cancer were observed, yielding a standardized mortality ratio of 1.93 (9 observed, 95% CI = 0.88, 3.67), which increased for those who had worked in areas with the highest lead exposure (8 observed, standardized mortality ratio = 2.39, 95% CI = 1.03, 4.71). Cerebrovascular disease remained elevated for those with more than 20 years of exposure (26 observed, standardized mortality ratio = 1.41, 95% CI = 0.92, 2.07). CONCLUSIONS: This cohort with high lead exposure showed a diminishing excess of death from nonmalignant renal disease, a continued excess from kidney cancer, and an excess of cerebrovascular disease only in those with longest exposure to lead. PMID- 1456338 TI - Assessing providers of coronary revascularization: a method for peer review organizations. AB - OBJECTIVES: Current methods to evaluate quality of care are usually limited to reviews of individual cases or comparisons of hospital mortality rates. We present an alternative method that compares complication rates adjusted for patient characteristics. METHODS: Detailed clinical data that were specifically designed for quality comparisons of providers of revascularization procedures were abstracted from the medical records of 1998 Medicare patients, in 16 hospitals, who had coronary artery bypass surgery and 2091 patients, in 16 hospitals, who had angioplasty. Providers were ranked on the basis of an unadjusted risk, a risk adjusted for detailed clinical information, and a risk adjusted only for patient comorbidities. RESULTS: Complication rates differed significantly and substantially among the hospitals. Clinical adjustment changed the hospital rankings for the bypass surgery hospitals, but not for the angioplasty hospitals. Adjustment for comorbidities did not affect hospital rankings for either procedure. CONCLUSIONS: When sample sizes are limited, adverse outcome rates may be a more sensitive measure of quality of care than mortality rates. Rates that are unadjusted or adjusted only for comorbidities may be inadequate for evaluating some providers of bypass surgery. PMID- 1456340 TI - US National Health Data on Asian Americans and Pacific Islanders: a research agenda for the 1990s. AB - OBJECTIVES: In spite of over 30 years of periodic nationwide surveys, we have thus far only the most rudimentary estimates of the determinants of the health of Asian Americans and Pacific Islanders. This paper explores ways to improve the capability of the National Center for Health Statistics (NCHS) to collect national health data on these populations. METHODS: The NCHS "race" coding practices are reviewed, their limitations stated, ways to improve the numerator and denominator data discussed, and a research agenda presented. RESULTS: Resources can be intensified to produce better denominator data, and to improve the collection of detailed ethnicity information for the numerators, in at least the three states (California, New York, and Hawaii) where the majority of Asian/Pacific Islanders lived in 1990. Subsequently, these efforts should be extended to the 10 states where 79% of these individuals reside or to the top 15 metropolitan areas where they are concentrated. CONCLUSIONS: If the recommendations are implemented, several coordinated multisite, multiwave epidemiologic surveys can be conducted using standardized interview instruments and data collection procedures that will capitalize on the geographic distribution of Asian/Pacific Islanders. PMID- 1456341 TI - Planning professional education at schools of public health. AB - OBJECTIVES: Professional education in public health should equip graduates with adequate knowledge and skills to manage diverse and complex problems. How best to address this challenge is widely debated. We describe the Harvard School of Public Health's self-evaluation and development of a practice-oriented program. METHODS: As part of Harvard's schoolwide review of the master of public health (MPH), self-administered questionnaires were distributed to all MPH students, 1987 to 1989, and international and US alumni, 1979 to 1986. Extensive discussions were conducted with relevant student and faculty groups. RESULTS: Survey results provided a basis for educational policy and curricular changes that culminated in a revised MPH that targets key areas of public health practice. Examples from the Harvard experience are provided. CONCLUSIONS: Information derived from student and alumni surveys can be highly effective in the process of guiding curricular change at schools of public health. This should be coupled with a strategic approach to gain faculty support for proposed innovations. Ongoing monitoring and modification of the new curriculum is essential. PMID- 1456343 TI - The social impact of dental problems and visits. AB - OBJECTIVES: The purpose of this analysis was to assess selected social consequences of maintaining oral health and treating oral diseases. The associations among socioeconomic and demographic factors with time lost from work or school and reductions in normal activities are explored. METHODS: Data were gathered as part of the 1989 National Health Interview Survey from 50,000 US households (117,000 individuals), representing 240 million persons. The oral health care supplement was analyzed using the software SUDAAN to produce standard errors for estimates based on complex multistage sample designs. RESULTS: Because of dental visits or problems, 148,000 hours of work were lost per 100,000 workers, 117,000 hours of school were lost per 100,000 school-age children, and 17,000 activity days beyond work and school time were restricted per 100,000 individuals in 1989. Exploratory analyses suggest that sociodemographic groups have different patterns of such time loss and of reduced normal activities. CONCLUSIONS: Overall, there is low social impact individually from dental visits and oral conditions. At the societal level, however, such problems and treatments among disadvantaged groups appear to have a greater impact. PMID- 1456342 TI - Ultraviolet light exposure and lens opacities: the Beaver Dam Eye Study. AB - OBJECTIVES: Exposure to sunlight may be a risk factor for the development of cataract. The relationships between exposure to sunlight and to the ultraviolet-B (UVB) component of light and the prevalence of lens opacities were examined in the Beaver Dam Eye Study. METHODS: Persons 43 to 84 years of age residing in Beaver Dam, Wisconsin, were examined using standardized photographic assessments of lens opacities. A questionnaire about medical history and exposure to light was administered. RESULTS: After adjusting for other risk factors, men who had higher levels of average annual ambient UVB light were 1.36 times more likely to have more severe cortical opacities than men with lower levels. However, UVB exposure was not found to be associated with nuclear sclerosis or posterior subcapsular opacities in men. Moreover, no associations with UVB exposure were found for women, who were less likely to be exposed to UVB. CONCLUSIONS: Exposure to UVB light may be associated with the severity of cortical opacities in men. However, the lack of an association in women, the group more likely to have cortical opacities, suggests that other factors may be more important in the pathogenesis of lens opacities. PMID- 1456344 TI - Lead exposure in the construction industry: results from the California Occupational Lead Registry, 1987 through 1989. AB - The construction industry is exempt from the medical monitoring portions of the US Federal Occupational Safety and Health Administration General Industry Lead Standard. Of 28 construction workers reported to the California Occupational Lead Registry through March 1989, 11 (39%) had blood lead levels of 2.90 mumol/L (60 micrograms/dL) or greater, the level at which immediate removal from lead exposure is mandated in nonconstruction industries. Many workers had not been warned of possible lead exposure. The exemption of the construction industry from the General Industry Lead Standard should be reconsidered. PMID- 1456345 TI - Potential lead exposures from lead crystal decanters. AB - We measured the concentrations of lead leached into 4% acetic acid, white port, and a synthetic alcoholic beverage that were stored in lead crystal decanters for 1-, 2-, and 10-day periods at room temperature. In decanters from 14 different manufacturers, measured lead concentrations ranged from 100 to 1800 micrograms/L. The pH of the leaching medium is probably the dominant factor determining the extent of lead leached, with greater leaching occurring at lower pH values. The consumption of alcoholic beverages stored in lead crystal decanters is judged to pose a hazard. PMID- 1456346 TI - Hair dye use and multiple myeloma in white men. AB - In recent reports, multiple myeloma has been linked to use of hair coloring products containing mutagenic and carcinogenic chemicals. A population-based case control study in Iowa of 173 White men with multiple myeloma and 650 controls obtained information on hair dye use. Risk of multiple myeloma was significantly elevated (OR = 1.9) among hair dye users and was greatest among those using hair dyes at least once a month for a year or more (OR = 4.3). These data, along with results from other studies, suggest that use of hair dyes contributes to the development of multiple myeloma. PMID- 1456347 TI - Men's disclosure of HIV test results to male primary sex partners. AB - We evaluated disclosure of human immunodeficiency virus (HIV) antibody status to a main sex partner and the impact on the relationship in men who have sex with men and who are enrolled in the Acquired Immunodeficiency Syndrome (AIDS) Community Demonstration Projects cohorts. Eighty-nine percent of both seronegative and seropositive men disclosed the results to their main sex partner. Seventy percent of the seronegative men and 82% of the seropositive men who did so reported that the relationship remained "as strong as ever" after 6 months. Most men who did not disclose their test results to their main partner reported being "single" after 6 months. PMID- 1456348 TI - Trends in tans and skin protection in Australian fashion magazines, 1982 through 1991. AB - We rated 3971 photographs of models from midsummer editions of six Australian fashion magazines from 1982-1983 to 1990-1991 for tan on a 9-point scale, for the presence of hats, for sun-protective clothing, and for shade setting. With the exception of the 1990-1991 sample, there was an increasing proportion of light tans over the years. Men were more likely to be deeply tanned than were women. The proportion of models wearing hats followed an increasing linear trend across the five periods. Three quarters of the outdoor photographs were taken in unshaded settings. In unshaded settings, 17% of the women and 5% of the men wore hats. PMID- 1456349 TI - The slavery hypothesis for hypertension among African Americans: the historical evidence. AB - The slavery hypothesis for hypertension has stated that the high blood pressures sometimes measured in African Americans are caused by one or more of these conditions: first, salt deficiency in the parts of Africa that supplied slaves for the Americas; second, the trauma of the slave trade itself; third, conditions of slavery in the United States. A review of the historical evidence shows that there was no salt deficiency in those parts of Africa, nor do present-day West Africans have a high incidence of hypertension. Historical evidence does not support the hypothesis that deaths aboard slave ships were caused mainly by conditions that might be conductive to hypertension, such as salt-depleting diseases. Finally, the hypothesis has depended heavily on evidence from the West Indies, which is not relevant for the United States. There is no evidence that diet or the resulting patterns of disease and demography among slaves in the American South were significantly different from those of other poor southerners. PMID- 1456350 TI - Measuring up: quality assurance for cholesterol screening programs in Ohio. PMID- 1456351 TI - Hispanic subgroups and intraracial comparisons. PMID- 1456352 TI - Handedness, accidents, and mental state. PMID- 1456353 TI - Denver's increase in HIV counseling after Magic Johnson's HIV disclosure. PMID- 1456354 TI - Magic Johnson's credibility among African-American men. PMID- 1456355 TI - Presidential address of the American Orthopaedic Society for Sports Medicine. Where do we go from here? PMID- 1456356 TI - Ultrasonography of chronic tendon injuries in the groin. AB - Ultrasonography was used in the diagnosis of 36 patients with chronic groin pain localized to the tendons of the rectus abdominis, rectus femoris, adductor muscles, hamstring muscles, and the gluteal muscles. Abnormal findings, such as focal sonolucent areas and discontinuity of tendon fibers, that are indicative of nonhealed partial ruptures were found in 28 patients. These findings differed clearly from the asymptomatic contralateral side, which was used for comparison. The abnormalities were located in three different sites: at the tendon insertion, within the tendon, and at the tendomuscular junction. Ten patients were treated surgically and the findings at surgery correlated well with the ultrasonographic findings of partial tendon tears: 9 were true-positive and 1 was a true-negative. Ultrasonography appears to be a valuable method in the diagnosis of chronic groin pain. PMID- 1456357 TI - Tenotomy of the adductor longus tendon in the treatment of chronic groin pain in athletes. AB - Eighteen tenotomies of the adductor longus tendon were performed in 16 consecutive male athletes (aged 20 to 42) as treatment for chronic groin pain. The criteria for surgery was a history of long-standing (range, 2.5 to 48 months) and distinct pain at the origin of the adductor longus muscle, refractory to conservative treatment. At followup 35 months (range, 4 to 84) after surgery, all patients were improved or free of symptoms. All but 1 of the athletes returned to the same sport within a mean of 6.6 weeks, and 12 of 16 returned to competitive sports within a mean of 14 weeks after surgery. A majority of the patients (10 of 16) returned to full athletic activity, whereas 5 of 16 performed at a reduced level. One patient discontinued his sports activity due to other causes. In conclusion, when conservative treatment fails, tenotomy of the adductor longus tendon gives good long-term functional results in the treatment of chronic groin pain that is localized at the origin of the adductor longus muscle. A decreased muscle strength was observed in this study and did not seem to influence participation in sports. PMID- 1456358 TI - Meniscal transplantation using fresh and cryopreserved allografts. An experimental study in goats. AB - A comparative study of three subgroups of meniscal transplants was undertaken in the goat model: Group 1 (autograft) involved removal and immediate reimplantation of the meniscus; Group 2, fresh meniscal allografts; and Group 3, cryopreserved (30 days) meniscal allografts. Six months after surgery, tissues were evaluated for gross degenerative changes, proteoglycan concentration (as assessed by uronic acid), water content, vascularity, histology, and cell viability. The contralateral knee served as control for all comparisons. There was no statistical difference in the amount of arthritis present and all transplants demonstrated an essentially normal peripheral vascularity compared to controls. Sections revealed reduced numbers of cells in the central portions of the transplanted menisci and these viable cells demonstrated different behavior in multiplication in tissue culture compared to contralateral controls. Grossly and microscopically, the implanted menisci differed little from the controls. The measurement of proteoglycan concentration and water content of the transplanted meniscal cartilage suggest alterations that may affect the long-term mechanical properties. The autograft specimens showed the water content was very slightly increased (3% to 6%), while the proteoglycan concentration was increased (42% in terms of uronic acid). In contrast, the water content of the fresh allograft group and the cryopreserved group was increased 12% to 24%. Proteoglycan concentration in these groups was decreased up to 56% in portions of some menisci compared to controls. Fresh and cryopreserved meniscal allografts showed peripheral healing, revascularization, cellularity, and incorporation, and grossly appeared good at 6 months in the goat model. The biochemical changes in the extracellular matrix at 6 months raises questions on the long-term function of these transplanted menisci. PMID- 1456359 TI - Outcome of conservative and surgical management of navicular stress fracture in athletes. Eighty-six cases proven with computerized tomography. AB - Eighty-two athletes with 86 clinical navicular stress fractures, all imaged with computerized tomography, were followed for an average of 33 months (range, 6 to 108) after diagnosis. Initial treatment consisted of at least 6 weeks of nonweightbearing cast immobilization for 22 fractures, at least 6 weeks of limitation of activity with continued weightbearing for 34 fractures, and a period of less than 6 weeks of conservative treatment for another 19 fractures. Five patients attempted to continue playing sports. Six patients had immediate surgery. Nineteen of 22 patients (86%) who had initial non-weightbearing cast immobilization treatment returned to sports, compared with only 9 of 34 patients (26%) who initially continued weightbearing with limited activity (P < 0.001). After failure of the latter treatment, successful outcomes were seen for 6 of 7 patients (86%) treated with nonweightbearing cast immobilization, while 11 of 15 patients (73%) who had one surgical procedure were able to return to sports. These results indicate that nonweightbearing cast immobilization is the treatment of choice for navicular stress fractures. Also, this treatment compares favorably with surgical treatment for patients who present after failed weightbearing treatments. Computerized tomographic appearances of healing fractures do not necessarily mirror clinical union, and postimmobilization management should be monitored clinically. PMID- 1456360 TI - Augmented repair and early mobilization of acute anterior cruciate ligament injuries. AB - This paper describes a technique for repair of the anterior cruciate ligament with protection of that repair by a synthetic augmentation device. Of 61 patients who underwent surgery 24 to 57 months (mean, 38.3) before data accumulation, 57 returned for followup. Subjectively, 53 (93%) patients reported a good or excellent functional result; however, only 29 (51%) of the patients returned to their preinjury sports level. Objectively, a radiographic Lachman test was performed on both the injured and the noninjured knee of all 57 patients. The preoperative mean difference between the knees was 8.6 mm (range, 4.6 to 17.2) and at followup it was 2.4 mm (range, -0.9 to 11.8). Radiographic abduction and adduction stress tests demonstrated stable healing of the (unrepaired) collateral ligament lesions (varus stress = 0.1 mm and valgus stress = 0.4 mm mean side-to side difference), indicating that suturing of ruptured collateral ligaments is not necessary when the knee is centrally stabilized with the augmentation device. These results indicate that successful repair of the anterior cruciate ligament is frequently possible when enhanced with an augmentation device. PMID- 1456361 TI - Static capsuloligamentous restraints to superior-inferior translation of the glenohumeral joint. AB - The purpose of this study was to determine the contributions of specific capsuloligamentous structures to restraining superior-inferior translation of the glenohumeral joint. Eleven cadaveric shoulders were tested using a four degrees of-freedom test apparatus. The humerus was free to translate in three planes and free to flex and extend when a superior and inferior force of 50 N was applied. Testing was performed in three positions of abduction (0 degree, 45 degrees, and 90 degrees) and three positions of rotation (neutral, maximum internal, and external). Shoulders were tested intact, vented, and after division of specific capsuloligamentous structures. The primary restraint to inferior translation of the adducted shoulder was the superior glenohumeral ligament. The coracohumeral ligament appeared to have no significant suspensory role. With progressive abduction, the anterior and posterior portions of the glenohumeral ligament become the main static stabilizers resisting inferior translation: the anterior portion was the primary capsular restraint at 45 degrees of abduction, while the posterior portion was the primary restraint at 90 degrees of abduction, neutral rotation. Our results indicate that clinical assessment of glenohumeral translation in the superior-inferior plane should be performed in multiple positions of abduction and rotation. PMID- 1456362 TI - A multivariate risk analysis of selected playing surfaces in the National Football League: 1980 to 1989. An epidemiologic study of knee injuries. AB - This study focuses on the injury rates for natural grass and AstroTurf surfaces and the risk factors of game position and type of play. We examined the game related knee sprains, medial collateral ligament sprains, and anterior cruciate ligament sprains that occurred in the National Football League during the 1980 to 1989 seasons. The findings are controlled for categories of severity (number of games missed due to injury), position, and situation (rushing or passing) at the time of injury. The analysis of the data incorporates epidemiologic techniques associated with incidence density ratios. The data show that there is a statistically significant difference between the higher AstroTurf injury rates for knee sprains. When knee sprains are separated into medial collateral ligament sprains and anterior cruciate ligament sprains, only the anterior cruciate ligament sprains show a statistically significant higher injury rate for AstroTurf. When simultaneous control variables are considered, significantly more knee sprains occurred to backs on rushing plays and linemen on passing plays. When controlling the data for severity, only the Category II injuries (three or more games missed) sustained by linemen on passing plays had statistically significant higher injury rates for the AstroTurf. For medial collateral ligament sprains, only the Category II injuries for linemen on passing plays remain statistically significant. The data for the ACL sprains show statistically significant differences between the injury rate on natural grass and the injury rate on Astro Turf under conditions of special teams play. PMID- 1456363 TI - A prospective comparison of computerized arthrotomography and magnetic resonance imaging of the glenohumeral joint. AB - Twenty-five patients with shoulder instability or shoulder pain of undetermined etiology were prospectively evaluated with magnetic resonance imaging and computerized arthrotomography. Actual lesions were determined by arthroscopy or at the time of open surgical repair. The images obtained were interpreted independently by three radiologists blinded to both surgical results and the results of previous diagnostic tests. Sensitivity, specificity, and accuracy were determined for each imaging technique for a variety of pathologic entities, including anterior and posterior labral abnormalities, capsular redundancy, biceps-labral complex abnormalities, humeral head (Hill-Sachs) impression lesions, and glenohumeral loose bodies. Analysis of imaging techniques also included construction of receiver operator curves for labral abnormalities. Magnetic resonance imaging showed better diagnostic results in the evaluation of glenoid labral and humeral head impression lesions (P < 0.05). Both imaging techniques were equally successful in identifying biceps-labral lesions and intraarticular loose bodies within the glenohumeral joint. Neither imaging technique was consistent in the evaluation of capsular redundancy. Receiver operator curve analysis confirmed that magnetic resonance imaging was the more accurate imaging study in evaluating anterior and posterior glenoid labral abnormalities. PMID- 1456364 TI - Arthroscopic labral debridement. A three-year follow-up study. AB - This is a retrospective review of 40 patients who underwent arthroscopic labral debridement of the shoulder. All patients were active participants in sports involving use of the shoulder. All patients presented with shoulder pain. Only 40% were found to have distinct glenohumeral instability on examination. At surgery, all patients had labral injury. Ten patients had anterosuperior labral tears, 20 had anteroinferior labral tears or detachments, and 10 had posteroinferior labral tears or detachments. Outcome was assessed at a minimum of 2 years (average, 43 months) postoperatively. Overall, only 7% of the patients had significant symptomatic relief at followup. However, 72% noted relief of symptoms during the 1st year after surgery, but there was deterioration over time. CONCLUSION: Arthroscopic labral debridement is not an effective long-term solution for symptomatic relief in the overhead athlete. PMID- 1456365 TI - The anterior cruciate ligament-deficient knee with varus alignment. An analysis of gait adaptations and dynamic joint loadings. AB - Thirty-two patients with an ACL-deficient knee and lower limb varus alignment and 16 healthy controls were analyzed during level walking using a force-plate and optoelectronic system. The forces and moments of the lower limb and knee joint were measured and knee joint loads and ligament tensile forces were calculated using a mathematical model. The majority of patients (20 of 32) had an abnormally high adduction moment at the affected knee. The adduction moment showed a statistically significant correlation to high medial tibiofemoral compartment loads and high lateral soft tissue forces, but not to the degree of varus alignment on standing roentgenograms. Fifteen of 32 knees had abnormally high lateral soft tissue forces. We interpreted these gait findings as indicative of a medial shift in the center of maximal joint pressure and an increase in lateral soft tissue forces to achieve coronal plane stability. Further, there is the likelihood of separation of the lateral tibiofemoral joint and "condylar lift off" during periods of the stance phase. If this occurs, all of the load-bearing forces would shift to the medial tibiofemoral joint and relatively large tensile forces would occur in the lateral soft tissue restraints. The flexion moment, as related to the quadriceps muscle force, was significantly lower than the control knees in 40% of the involved knees, and the extension moment, as related to the hamstring muscle force, was significantly higher in 50% of the involved knees. We interpret this finding as a gait adaptation tending to diminish quadriceps muscle activity and enhance hamstring muscle activity to provide dynamic anteroposterior stability of the knee joint. The fundamental assumption of this paper is that any combination of conditions leading to higher medial joint forces is associated with factors leading to more rapid degeneration of the medial compartment in patients with ACL deficiency, varus deformity, and lax lateral ligaments. PMID- 1456366 TI - Psychological moods and subjectively perceived behavioral and somatic changes accompanying anabolic-androgenic steroid use. AB - To assess physiological and psychological states accompanying anabolic-androgenic steroid use, male weight lifters 1) were interviewed regarding their physical training and the patterns and effects of any drug use; 2) completed a written physical and medical history questionnaire, a Profile of Mood States questionnaire, and the Buss-Durkee Hostility Inventory; and 3) were physically examined, including a blood sample and urinalysis. Subjects were divided into current anabolic-androgenic steroid users (N = 12), previous users (N = 14), and nonusers (N = 24). Current and previous users reported the following changes associated with anabolic-androgenic steroid use: increases in enthusiasm, aggression, and irritability; changes in insomnia, muscle size, muscle strength and density; faster recovery from workouts and injuries; and changes in libido. We were unable to confirm these interview and physical and medical history questionnaire responses using standardized and well-accepted psychological inventories. There were no significant differences among groups for any Profile of Moods factor, total mood disturbance, total Buss-Durkee Hostility Inventory score, or any subscale. For current users, there were no significant correlations between either total weekly drug dose or length of time on the current cycle of anabolic-androgenic steroids and any individual scale of the Profile of Mood States, Buss-Durkee Hostility Inventory, Profile of Mood States total mood disturbance, or composite Buss-Durkee Hostility Inventory score. Furthermore, anabolic-androgenic steroid users did not differ in their responses on these inventories from nonusers or from general population norms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456367 TI - The repair of osteochondral defects using an exogenous fibrin clot. An experimental study in dogs. AB - To evaluate the ability of an exogenous fibrin clot to hasten or optimize the repair of full-thickness articular cartilage defects, 4-mm diameter, full thickness articular cartilage defects in 20 adult mongrel dogs were packed with an exogenous fibrin clot that had been prepared from each animal. The defects were created in a loaded and unloaded portion of the femoral trochlea. The healing response was then examined using routine histology at various intervals from 2 weeks to 6 months. Both the experimental (clot-filled) and control (empty) defects healed through a proliferation of fibrous connective tissue that eventually modulated into fibrocartilage. However, in the 2-, 4-, and 8-week animals, the experimental defects (both loaded and unloaded) demonstrated a more organized and advanced healing response than did the control defects. This difference was less pronounced in the 12- and 24-week animals. In all specimens, the clot-filled defects healed more uniformly than controls with less surface depression. In general, the unloaded sites were more uniform in healing than the corresponding loaded sites. PMID- 1456368 TI - Magnetic resonance imaging of the posterior cruciate ligament. Clinical use to improve diagnostic accuracy. AB - This study was undertaken to determine the accuracy of magnetic resonance image scanning in detecting posterior cruciate ligament injury, and to determine those clinical situations where it can add the most useful information. A retrospective study was conducted on 201 patients who underwent surgery after magnetic resonance scanning of their knees. Two additional patients who did not have surgery but had clinical findings grossly positive for posterior cruciate ligament injury were included in the analysis of magnetic resonance imaging accuracy. In all, there were 190 intact and 13 torn posterior cruciate ligaments. In a review of the clinical findings in the 11 patients with surgically documented tears, we found that all 11 had positive magnetic resonance scans. In 4 of the 11, magnetic resonance imaging provided especially useful information regarding the status of the ligament. For the 190 normal ligaments, there were no false-positive scans; for the 13 torn ligaments, there were no false-negative scans. Therefore, specificity and sensitivity estimates for this group were both 100%. Magnetic resonance imaging proved to be an accurate modality for evaluating the integrity of the posterior cruciate ligament. If used in the proper setting, it can provide useful information for diagnosing posterior cruciate ligament injuries. PMID- 1456369 TI - The effect of harvesting the central one-third of the patellar tendon on patellofemoral contact pressure. AB - This study assessed whether removing the central one-third of the patellar tendon, with or without side-to-side repair of the patellar tendon defect, would alter patellofemoral pressure. Patellofemoral pressure was assessed by testing five stable knees from five different cadaveric donors on a specially designed hydraulic knee machine. Patellofemoral joint pressures were measured by placing pressure-sensitive film into the patellofemoral articulation. The joint was loaded in a static fashion, with quadriceps forces consistent with walking (647 N) and stair climbing (1923 N), at 30 degrees, 60 degrees, and 90 degrees of knee flexion. Using the same knees, the central one-third of the patellar tendon was then sectioned, and patellofemoral joint pressure measurements were repeated at identical knee flexion angles and quadriceps-forces. Side-to-side repair of the patellar tendon defect was performed and patellofemoral joint pressure measurements were repeated. There were no statistically significant differences between the control and sectioned values or between the control and repaired defect values. These results suggest that harvesting the central one-third of the patellar tendon--with or without side-to-side repair of the patellar tendon defect--does not alter patellofemoral pressures. PMID- 1456370 TI - A biomechanical evaluation of the iliotibial tract screw tenodesis. AB - Biomechanical testing of the iliotibial tract screw tenodesis was performed in 10 cadaveric knees under forces approximating in vivo conditions. Force versus displacement curves at various flexion angles were generated with the anterior cruciate ligament intact, with the anterior cruciate ligament sectioned, and after the iliotibial tract screw tenodesis had been performed. Displacement force was measured to 5, 10, and 15 mm. The iliotibial tract screw tenodesis was ineffective in reducing anterior translation of the tibia in the anterior cruciate ligament-deficient knee at forces approximating in vivo conditions. PMID- 1456371 TI - Anterior compartment pressures in cross-country skiers. A comparison of classic and skating skis. AB - This paper compares the pressure changes in the anterior compartment of the leg when cross-country skiing using the skating method on either skating skis or classic skis. Intracompartmental pressures of the right leg were recorded from the tibialis anterior muscle of 10 subjects at rest and 15 seconds after 10 to 12 minutes of cross-country skiing on a designated course. All subjects completed two trials on different days. In one trial, subjects used skating skis and for the other trial, classic skis were used for the skating technique. Although the average pressure increase was higher for the classic ski trials than for the skating ski trials, the difference was not significant. This finding indicates that cross-country skiers who skate on a classic ski as opposed to a shorter skating ski do not experience a significantly greater increase in their anterior compartment pressure. Thus, it appears that the type of ski used is not the most significant factor contributing to chronic compartment syndrome. PMID- 1456372 TI - Characteristics of the isokinetic performance of patients with injured cruciate ligaments. AB - The torques of the quadriceps muscle in patients with cruciate ligament injuries were evaluated under isokinetic contraction. There were 30 patients with anterior cruciate ligament injuries, 19 with posterior cruciate ligament injuries, and 30 controls. The torques of concentric and eccentric contractions in anterior cruciate ligament-injured knees showed a significant difference from those in the uninjured sides at extension angles of less than 45 degrees, yet the values of the peak torques for concentric and eccentric contractions were the same as those for the uninjured sides. The torques of concentric and eccentric contractions in posterior cruciate ligament-injured knees showed a significant difference from the uninjured sides at flexion angles of more than 36 degrees. The peak torques for concentric and eccentric contraction also showed a significant difference from the uninjured sides. The concentric and eccentric peak torque angles of the injured knees were similar to those of the uninjured sides in all subjects. The ratios of eccentric to concentric peak torque of the contralateral knees in the anterior cruciate ligament-injured groups did not show a significant difference from those of the controls. The evaluation of the biomechanical change in these categories is of great advantage in determining proper methods of treatment and rehabilitation. PMID- 1456373 TI - Patellar stress fracture. PMID- 1456374 TI - Stress fractures of the tarsal navicular. A case report. AB - In summary, the diagnosis of a tarsal navicular stress fracture should be entertained in the athlete with ill-defined midfoot pain. Technetium bone scans will often point the clinician in the right direction; biplanar CT scans will pin point the diagnosis and can be invaluable in perioperative planning. Subsequent treatment, however, must be determined on a clinical rather than a radiographic basis. PMID- 1456375 TI - Stress fracture of the sacrum. PMID- 1456376 TI - Stress fracture of the right distal femur following bilateral fractures of the proximal fibulas. A case report. PMID- 1456377 TI - Dislocation of the tibialis posterior tendon. PMID- 1456378 TI - Volunteer physicians working with the United States Olympic Committee. PMID- 1456379 TI - Anterior-posterior and rational displacements of the tibia elicited by quadriceps contraction. PMID- 1456380 TI - Alternating hemiplegia in childhood: 23 cases in Japan. AB - Alternating hemiplegia in childhood (AHC) has clinically characteristic features which are easily defined and recognizable. Laboratory investigations were basically normal although they were extensively examined during and between attacks. There is still much debate about its etiology, particularly its relation to migraine or epilepsy. Clinical characteristics of identified 23 AHC in Japanese were presented, which were obtained from a large Japanese cooperative study in 1988. AHC may prove not to be as rare as has been thought. PMID- 1456381 TI - Inter- and intra-observer agreement in the assessment of the quality of spontaneous movements in the newborn. AB - The inter- and intra-observer agreement for the assessment of several aspects of the quality of spontaneous movements in newborn infants was analysed by 4 observers. The agreement rates were corrected for chance by the use of kappa statistics, which revealed kappa values ranging from 0.36 to 0.84. The degree of agreement on various items differed. A moderate-to-good agreement was found for the items "onset of movement," "speed," "speed of arms compared to legs," "amplitude of arms compared to legs," "fluency," "variability in arm patterns" and "global judgement of the movement" (kappa values ranging from 0.51 to 0.84). Less agreement occurred in the items "amplitude," "variability in movement pattern" and "variability in leg patterns" (kappa values ranging from 0.36 to 0.40). Even though it is believed that the qualitative assessment of spontaneous motor behaviour is very subjective, our results suggest that several qualitative aspects of infant motor behaviour can be reliably judged. We concluded that the global judgement of the quality of general movements in full-term infants is a reproducible, and therefore reliable, clinical tool for evaluating the function of the central nervous system in the neonatal period. PMID- 1456382 TI - Primitive reflex profiles in infants: differences based on categories of neurological abnormality. AB - In order to clarify reflex profiles in the first year of life in connection with categories of neurological abnormality, six primitive reflexes, i.e., the crossed extensor reflex, suprapubic extensor reflex, heel reflex, Galant response, asymmetric tonic neck reflex and plantar grasp response, were examined in 458 normal infants, 78 infants with cerebral palsy (CP) and 81 infants with mental retardation (MR), whose diagnoses were confirmed at a later follow-up examination. The change in the mean score for each of these reflexes with age was characteristic for each category or type of neurological abnormality. This implies that a presumptive diagnosis can be made in neurologically high-risk infants by examination of the primitive reflexes. Such reflexes are therefore of specific significance, among other neurological criteria, in infants within the first year of life. PMID- 1456383 TI - Early diagnosis of severe myoclonic epilepsy in infancy. AB - Of 329 epileptic patients referred in a six year period with the first seizure occurring in the first year of life, 20 met the following criteria: generalized seizures excluding infantile spasms, myoclonic, tonic or absence seizures, at least one afebrile seizure, normal development prior to the first seizure, normal CT scan, and no etiology. Seventeen of these 20 patients developed the full pattern of severe myoclonic epilepsy in infancy (SMEI). This syndrome was recognizable from the second or third seizure in the first year of life, although epileptiform EEG abnormalities were lacking until the age of 11 to over 30 months. Therefore, based on the clinical pattern, the diagnosis of SMEI can be made with quite good reliability by the end of the first year of life. PMID- 1456384 TI - A comparative clinical and pharmacokinetic study of a new slow-release versus conventional preparations of valproic acid in children with intractable epilepsy. AB - Thirteen children with intractable epilepsy were treated by means of three-times daily administration of a conventional preparation of valproic acid (C-VPA) and twice-daily administration of a new slow-release preparation of VPA (SR-VPA) with the cross-over technique. The frequency of seizures, side effect and steady-state pharmacokinetics of VPA were evaluated. With the change from C-VPA tid to SR-VPA bid, four patients exhibited a significant reduction in seizure frequency. The steady-state minimum concentration (Cmin) was higher, the maximum concentration (Cmax) lower and there were less diurnal fluctuations with SR-VPA, than with the respective values obtained in the C-VPA group, all the differences being statistically significant. Furthermore, a significant difference was unexpectedly found in the area under the curve (AUC) from 0 to 24 hours, the mean AUC in the period of SR-VPA being 9% higher than that with C-VPA. Five of the nine patients under 6 years of age showed more than 10% increase, and all four patients over 6 years of age less than 10% increase or a decrease in AUC. It was concluded that with SR-VPA bid, the pharmacokinetic features were more stable, the age-related AUC value was larger and the clinical effect was better than in comparison to C VPA tid in children with intractable epilepsy. PMID- 1456385 TI - Nitrazepam-induced cricopharyngeal dysphagia, abnormal esophageal peristalsis and associated bronchospasm: probable cause of nitrazepam-related sudden death. AB - Nitrazepam was used in the treatment of resistant myoclonic epilepsy in 38 children. After the occurrence of nitrazepam-associated swallowing incoordination, high-peaked esophageal peristalsis and related bronchospasm in one patient, we initiated a prospective study of esophageal manometry using a station pull-through technique with a pediatric 4-channel continuous perfusing system. Three more patients were found to have delayed cricopharyngeal relaxation and high-peaked esophageal peristaltic waves. The initial patient developed severe respiratory distress and bronchospasm necessitating ventilatory support while on nitrazepam and improved dramatically with subsequent normal manometric study following nitrazepam discontinuation. Nitrazepam was reintroduced for its anticonvulsant and cognitive benefits and was tolerated at a reduced dosage. We postulate a central nervous system effect of nitrazepam promoting parasympathetic overactivity or vagotonia which can cause potentially fatal respiratory distress. Care must be exercised in nitrazepam use and esophageal manometry may be helpful in defining patients at greater risk for sudden death. PMID- 1456386 TI - Somatosensory evoked potentials and nerve conduction studies in patients with Guillain-Barre syndrome. AB - Somatosensory evoked potentials, F-waves, and nerve conduction studies (NCS) were performed to determine their usefulness in detecting electrophysiologic abnormalities in 23 children in the acute stage of Guillain-Barre syndrome. The studies were performed on average 8.3 days after the onset of neurological symptoms, before the period of maximal weakness. All patients had at least one abnormal test. Somatosensory evoked potentials (SEP) showed most abnormalities: 91% abnormal recordings with posterior tibial nerve (PTN) stimulation and 68% with median nerve (MN) stimulation. The nerve conduction velocities were abnormal in 76% and 67% with PTN and MN stimulation, respectively. The F-waves were abnormal in 66% (PTN) and 56% (MN). The SEP studies were helpful in detecting proximal and central conduction abnormalities in 26% of patients, and they were more sensitive in detecting an abnormality when compared with F-wave recordings. Furthermore, in one patient with normal NCS and F-waves the prolonged lumbar potential-P35 conduction time of the PTN-SEP was the only abnormality found. SEP can detect an abnormality and thus support the clinical diagnosis of Guillain Barre syndrome in the acute stage when the results of more conventional tests are inconclusive. PMID- 1456387 TI - Prevention of myonecrosis in mdx mice: effect of immobilization by the local tetanus method. AB - Sixteen mdx mice of three-week-old were injected with tetanus toxin into the right gastrocnemius muscle and then subjected to sustained dorsiflexion of the right ankle joint (local tetanus) for 2 to 56 days. Another 16 mdx mice of the same age were not injected with tetanus toxin, serving as controls. The incidence of centronucleated muscle fibers, which indicate preceding myodegeneration, was significantly reduced in the tetanus toxin injected soleus muscle (SOL) and extensor digitorum longus muscle (EDL), compared with that in the untreated control mdx mice. It seems that myonecrosis in the mdx mouse is facilitated by muscle movement itself and that immobilization of muscle prevents myonecrosis. This concept is helpful for understanding the mechanism underlying myonecrosis in patients with Duchenne muscular dystrophy, and for instruction concerning rehabilitation programs and activities in daily life. PMID- 1456388 TI - Epilepsia partialis continua and neuronal migration anomalies. AB - Neuronal migration anomalies commonly cause seizures that are partial in type and generally refractory to medical treatment. Epilepsia partialis continua (EPC), an unusual form of epilepsy commonly related to acute damage of the cerebral cortex or to a chronic lesion, has never been described in a patient with neuronal migration anomalies. In 50 children with epilepsy due to neuronal migration anomalies, we observed two cases of EPC. These two children had unilateral neuronal migration abnormalities with partial seizures other than EPC and contralateral hemiparesis. Epilepsia partialis continua appeared two to three years after the onset of partial attacks and was accompanied by a worsening of the children's previous hemiparesis. Although a rare seizure manifestation in children with neuronal migration anomalies, when it does appear, EPC can aggravate the clinical neurological condition and should always be investigated for in these cases. Because its clinical appearance is often subtle, as in these two children, EPC may easily remain undiagnosed. PMID- 1456389 TI - Relative hypoxia of the extremities in Fabry disease. AB - A purine degradation study, thermography and near infrared spectroscopy of the extremities were performed on 2 young males with Fabry disease and 2 healthy controls. Two-minute semi-ischemic forearm exercise caused a distinct increase in lactate in all subjects, but venous hypoxanthine and ammonia were greatly increased only in the Fabry patients, suggesting a relatively hypoxic state of the extremities. Limb thermograms of the patients revealed glove and stocking type disturbance at rest. Poor recovery of the skin temperature of the hands and forearms after exercise was observed in the patients, but the sharp increase in oxygenated hemoglobin after total ischemia was found to be normal or near infrared spectroscopy. Neurotropin showed an analgesic effect, i.e. a strong and selective heat-productive action on the painful lesions, and suppressed the hypoxanthine level after exercise in 1 patient. Although the pathophysiology of the pain in Fabry disease has not been clearly elucidated, a relatively hypoxic state with peripheral hypothermia might play an important role in triggering of a painful attack or chronic burning paresthesia. PMID- 1456390 TI - Clinical variation within sibships in Fukuyama-type congenital muscular dystrophy. AB - A family in which three siblings were affected with severe cerebral malformations in association with ocular anomalies and muscle disease is reported. One sibling was diagnosed as having Fukuyama type congenital muscular dystrophy (FCMD) because he showed severe hypotonia with dystrophic findings on a muscle biopsy in addition to pachygyria on CT. At the age of 3 years, retinal detachment developed in both eyes. Another sibling exhibited at birth such characteristic features as pachygyria, cephalocele, hydrocephalus, retinal detachment in both eyes, elevated serum creatine kinase activity and arthrogryposis multiplex congenita. We consider these findings to be more consistent with Walker-Warburg syndrome (WWS) than with FCMD. Anencephaly found in the third sibling was regarded as WWS with extreme brain abnormality. The appearance of two syndromes (FCMD and WWS) in the three members of the same family suggests that these syndromes could be allelic with variable phenotypes. PMID- 1456391 TI - Epilepsia partialis continua and other seizures arising from the precentral gyrus: high incidence in patients with Rasmussen syndrome and neuronal migration disorders. PMID- 1456392 TI - Commentary: epilepsia partialis continua and neuroblast migrational disorders. PMID- 1456393 TI - A comparison of neuropsychological and psychosocial functioning after prophylactic treatment for childhood leukemia in monozygotic twins. AB - Outcome findings based on a comprehensive battery of neuropsychological and psychosocial measurements were compared for a set of monozygotic twins. One twin had been diagnosed with acute lymphoblastic leukemia and given prophylactic treatment involving intrathecal methotrexate. Her twin sibling, who developed no signs of the disease, served as a unique control. Remarkably similar profiles were noted for the twins on tests of nonverbal intelligence, visual memory, visual attention, psychomotor speed, and mental flexibility. All performances were in the average to high average range. Significant differences were found on tasks measuring verbal abstract reasoning skills. These differences were postulated to result from prophylactic treatment, leukemia itself, or disruption in normal psychosocial development. As in previous studies, problems with auditory attention were found. However, both children displayed attentional difficulties regardless of treatment status. Emotional assessment indicated that both twins were experiencing a clinically significant level of anxiety that was postulated to play a role in reduced attention skills. Findings argue for the continued need for monitoring the neuropsychological functioning of children given prophylactic treatment and demonstrate the importance of measuring emotional factors in assessment with these children. PMID- 1456394 TI - Dyskeratosis congenita: clinical and genetic heterogeneity. Report of a new case and review of the literature. AB - Dyskeratosis congenita (DC) is a rare form of ectodermal dysplasia consisting of dystrophic nails, hyperpigmentation, and leukoplakia often associated with aplastic anemia. DC is considered to be an X-linked recessive trait, but affected females suggest genetic heterogeneity. We report an additional female with DC and review the world literature, indicating transmission in X-linked recessive, autosomal recessive, and autosomal dominant manners. The clinical and genetic aspects of DC are heterogeneous, and different patterns of inheritance are associated with distinct clinical manifestations. DC should be considered in the diagnosis of a patient with any features of the syndrome regardless of gender. Conversely, DC should be considered in patients with aplastic anemia at any age. PMID- 1456395 TI - A phase I study of interleukin-2 in children with cancer. AB - Recombinant interleukin-2 (IL-2) produces clinical responses in approximately 20% of adult patients with renal cell carcinoma and melanoma, with both high-dose bolus and continuous infusion regimens. Because of the lower toxicity of continuous infusion, we elected to investigate in a Phase I trial a 5-day continuous infusion repeated for three weeks in children with malignancies refractory to standard therapy. Nineteen children with solid tumors and eight children with hematologic malignancies were entered into the study. The maximum tolerated dose was 3 x 10(6) U/m2/day, with dose-limiting toxicities occurring in five of seven patients treated at the 5 x 10(6) U/m2/day dose level. Dose limiting toxicities included hypotension, hyperbilirubinemia, thrombocytopenia, pulmonary/pleural effusion, and nephrotoxicity. Serum IL-2 levels were detectable at the higher dose levels and were comparable to those observed in adult patients. Hematologic changes at the higher dose levels included rebound lymphocytosis occurring within 48 h of discontinuation of IL-2, eosinophilia, and decreased platelet counts. No objective responses to therapy were seen. We have identified a dose and schedule of administration for IL-2 in pediatric patients that can be given without intensive care unit support. Pediatric Phase II trials examining the anti-tumor activity of IL-2 given by this schedule are in progress. PMID- 1456396 TI - Screening for neuroblastoma in North America. 2-year results from the Quebec Project. AB - The Quebec Neuroblastoma Screening Project was initiated to assess the clinical and biological aspects of screening infants for the presence of neuroblastoma in North America. All children born in the province of Quebec from May 1, 1989 to April 30, 1994 are eligible for participation. This report provides results from 22 months' accrual of infants who were screened using urine-saturated filter paper for determination of the catecholamine metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA). More than 157,000 infants have been screened to date at 3 weeks of age, representing 92% of the entire birth population of Quebec. Over 98,000 infants have been screened a second time at 6 months of age, which made up 76% of the Quebec birth cohort. After a two-stage initial screening, 340 (0.13%) infants (182 at 3 weeks and 158 at 6 months) required second laboratory examinations because of elevated levels of urinary VMA, HVA, or both. Twenty infants from the 3-week screening (0.01%) and nine from the 6-month screening (0.01%) were subsequently referred to one of four Quebec pediatric oncology centers for neuroblastoma evaluation. Seven of 20 children from the 3 week screening and two of nine children from the 6-month screening have been identified as having neuroblastoma. During the same period, 14 additional children in the birth cohort were diagnosed clinically with neuroblastoma; eight were diagnosed prior to screening at 3 weeks of age, three children had negative results at 3 weeks of age, two had negative results at 3 weeks and at 6 months of age, and one had never been screened.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456397 TI - Past and future of neuroblastoma screening in Japan. AB - In Japan, neuroblastoma is a common malignant tumor for children and its prognosis is unfavorable. Since this tumor excretes excessive amounts of vanillylmandelic acid (VMA) and homovanillic acid (HVA), catecholamine metabolites, into urine, both are sensitive diagnostic markers for neuroblastoma. In 1974, to improve the prognosis for neuroblastoma, a mass screening program by a qualitative VMA spot test for early detection of this tumor for 6-month-old infants was started in Kyoto, Japan. Subsequently, mass screening was also conducted in other areas in Japan. In 1985, mass screening commenced as a nationwide program throughout Japan, and in 1988, screening by quantitative measurement of VMA, HVA, and creatinine was recommended by the Ministry of Health and Welfare. During the 6 years from 1984 to 1989, 468 cases of neuroblastoma were detected from among 5,052,165 infants screened by this program. Analysis of findings in the 357 cases detected by mass screening from its inception in Kyoto until December of 1988 have been presented. The survival rate for these cases was 97% (348 of 357 cases). The prognosis of tumors detected by mass screening has clearly been favorable. In addition, survival rates were improved for all cases of neuroblastoma in Kyoto after the introduction of mass screening. The increased incidence of neuroblastoma in infants and the change in age distribution of all cases of neuroblastoma following the inception of urinary screening as well as the occurrence of spontaneous regression of neuroblastoma in relation to the screening program are discussed. Future problems facing mass screening for neuroblastoma are also presented. PMID- 1456398 TI - Mass screening of neuroblastoma in Sapporo City, Japan. AB - In Sapporo City a mass screening program for neuroblastoma aiming at 6-month-old infants has been performed since April 1981. By March 1990, 136,001 infants were screened; 26 true-positive cases of neuroblastoma and six false-negative cases were detected. The sensitivity of the mass screening method was about 80% throughout the 9 years. During the 9-year period, a total of nine children with neuroblastoma who were not screened were also identified. Clinical stage, age at diagnosis, and survival rate for the 32 patients who were screened (26 true positives and six false negatives) were much more favorable than those for the nine patients who were not screened. A remarkable decrease in the incidence of cases of neuroblastoma with advanced clinical stages over 1 year of age, especially among children 1-4 years of age, was noted after the start of the mass screening. The mortality from this tumor in children up to 4 years of age significantly decreased after the start of the urinary screening program. Rescreening at 14 months of age was begun in April, 1991 in Sapporo City. Performing two screening examinations decreases the probability of overlooking a patient. Thus, it is expected that tumors missed on the first screening would be detected by the second screening. PMID- 1456399 TI - Screening for neuroblastoma in the northern region of England. Laboratory aspects. AB - Our pilot study for neuroblastoma screening started in 1986. The study has progressed through several phases, with use of several analytical methods to a procedure based primarily on the use of automated gas chromatography mass spectrometry. The northern region of England has a relatively static population of approximately 3.5 million, with an annual birth rate of 41,000. The region consists of 16 administrative health districts. In 4 years, we have screened 20,829 infants from four health districts. In this program, we screen all children at 6 months of age. A urine sample is collected on filter paper by a health visitor, either at the time of the infant's routine clinic visit or during the health visitor's follow-up visit at home. In the laboratory, the sample is dried and processed for analysis of homovanillic acid (HVA) and vanillylmandelic acid (VMA), using a benchtop Hewlett Packard gas chromatograph mass spectrometer. The results are related to the creatinine content of the urine. Using cut-off limits of 39 micrograms/mg of creatinine for HVA and 25 micrograms/mg of creatinine for VMA, 2,537 infants (12.2%) required a second paper sample and 527 infants (2.5%) were observed with a liquid urine collection. Of these, the conditions of nine infants with elevated levels of HVA or VMA were investigated clinically for the possible presence of neuroblastoma. Two infants were found to have neuroblastoma; the other seven showed no evidence of tumor. In addition, there were three children who, when screened at 6 months of age, had normal levels of HVA and VMA but in whom neuroblastoma subsequently developed. PMID- 1456400 TI - A pilot study of screening for neuroblastoma in the north of England. AB - A pilot study has been carried out to assess the feasibility of screening for neuroblastoma in 6-month-old infants in the north of England. A total of 20,829 infants were screened. Two true-positive cases were found, along with eight false positive and three false-negative cases. It was shown that the concentrations of catecholamine metabolites in the urine are dependent on the creatinine content; centiles have been established to allow this relationship to be taken into account. Five of the eight false-positive cases would have been correctly assessed as normal if the new centiles had been used. Preliminary results lend support to the need for a well-designed study of neuroblastoma screening to be carried out, with death from this disease as the only end point. PMID- 1456401 TI - Biology of neuroblastomas in Japan found by screening. AB - Between June 1983 and December 1990, cytogenetic analysis was performed on 82 neuroblastoma patients, including 41 patients found by mass screening. The N-myc copy number was determined in 77 of the 82 patients. Patients were classified into three groups: patients found by mass screening (group A) (n = 41), patients found clinically who were under 12 months of age (group B) (n = 12), and patients found clinically who were over 12 months of age (group C) (n = 29). All patients in group A had hyperdiploid (H-2n) or near-triploid (3n) karyotypes; they were all completely free of tumor for 4-84 months after diagnosis, although one patient relapsed and attained complete remission again. Among those in group B, one patient with a stage 4 tumor had a near-diploid Karyotype (2n) and N-myc amplification, and died 18 months after diagnosis. Another patient aged 2 days with a stage 4S tumor had near-diploid karyotype and N-myc amplification, and died 9 months after diagnosis. Tumors in the remaining 18 patients in group B had hyperdiploid or near-triploid karyotypes, they lacked N-myc amplification, and the patients were free of tumor for 12-89 months after diagnosis. All patients in group C except two have near-diploid or hypotetraploid karyotypes, and 21 of 29 patients died within 18 months. One 13-month-old patient (classified in stage 2) and another 7-year-old patient (stage 2) had near-triploid karyotypes and were alive at 74 and 72 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456402 TI - Prolonged clinical response to vincristine treatment in two patients with idiopathic hypereosinophilic syndrome. AB - Idiopathic hypereosinophilic syndrome (HES) is a rapidly progressive disease that can result in death within weeks to months of diagnosis in untreated patients. We report two pediatric cases of HES. One patient has remained clinically and hematologically stable for 9 years with vincristine and 6-thioguanine (6TG), and the other has received vincristine alone for 6 months with a good response. The use of long-term vincristine and 6TG or vincristine alone has not been previously reported in the management of HES in children. Vincristine administered every 3-4 weeks with or without 6TG can produce a reduction in the overall white cell count and improvement of symptoms of hypereosinophilia. Although the mortality of patients with HES is high, aggressive treatment can result in significant clinical benefit and improved prognosis in children with this syndrome. PMID- 1456403 TI - Multiple relapses of Clostridium difficile-associated diarrhea in a cancer patient. Successful control with long-term cholestyramine therapy. AB - Clostridium difficile-associated diarrhea (CDAD) is caused by a toxin elaborated by the anaerobic organism Clostridium difficile. Although the vast majority of CDAD cases are now associated with antibiotic use, the administration of antineoplastic agents alone can result in clinical manifestations. While therapy with oral vancomycin is usually successful, one quarter of patients will relapse. We describe a 16-year-old girl with osteogenic sarcoma whose therapy was significantly complicated by multiple relapses of CDAD. All resulted in hospital admission. She failed several standard therapies for relapsed CDAD and was cured only after prolonged cholestyramine therapy. A subset of multiply relapsed CDAD patients may require prolonged therapy with cholestyramine to control the disease. PMID- 1456404 TI - Prevalence of anemia and malnutrition in a hospital-based population of children in India. PMID- 1456405 TI - A sensitive enzyme-linked immunosorbent assay for determination of bovine beta lactoglobulin in infant feeding formulas and in human milk. AB - We developed a sensitive sandwich-type ELISA for measuring low levels of cow's milk (CM) beta-lactoglobulin. Purified anti-beta-lactoglobulin was used as coating antibody and also as second antibody conjugated with alkaline phosphatase. Polyethylene glycol 6000 was added to the incubation buffers to improve sensitivity. The detection limit of the assay was 0.002 microgram/l, which is much better than sensitivities reported for other beta-lactoglobulin assays. The sensitivity was not impaired by the presence of other CM proteins. The recovery from breast milk was 93% and from the diluting buffer 127%. The coefficient of variation within day was 5-15% and between days 10%. One hour after oral intake of milk, beta-lactoglobulin could be detected in the breast milk of three mothers at concentrations of about 1-2 micrograms/l. Widely different concentrations of beta-lactoglobulin were measured in two protein hydrolysates based on CM whey and casein proteins; the observed concentrations were 200 and 0.0056 micrograms beta-lactoglobulin/g dry weight, respectively. PMID- 1456406 TI - Reduction of indoor airborne mould spores. AB - In 23 dwellings in Copenhagen high concentrations of airborne mould spores were shown by the "open Petri dish" method. The families were instructed how to reduce this contamination. One year later the number of mould spores was estimated again. At that time their number was 1/10 of that shown at the first sampling in 11 dwellings, and in 7 dwellings the reduction of mould spores decreased to 1/5. Only one dwelling showed no reduction. PMID- 1456407 TI - Allergenic pollens and pollinosis in Italy: recent advances. AB - The authors have mapped the occurrence of allergenic pollens throughout Italy and defined their most common clinical symptoms. To obtain an accurate aerobiological and clinical picture of such a geographically complex country as Italy, a detailed investigation was carried out involving 80 data-gathering stations and 40 clinical centers nationwide. Three main pollination periods can be distinguished: winter-pre-spring (January to March) for Betulaceae, Corylaceae, Cupressaceae, Salicaceae and Ulmaceae: spring-summer (April to June) for Gramineae, Urticaceae, Oleaceae, Plantago, Fagaceae, Pinaceae and Polygonaceae, and summer-autumn (August to September) for Urticaceae, Compositae and Chenopodiaceae. Examination of 49,660 patients affected by pollinosis (conjunctivitis, rhinitis, asthma, with positive skin tests or IgE-specific serum determination: RAST, ELISA) throughout Italy revealed sensitivity to Gramineae in 64.6%, to Parietaria in 36.7% to Olea in 15.8%, to Compositae in 13.2%, to Betulaceae-Corylaceae in 7% and to Fagaceae-Cupressaceae-Plantago in 4%-10%; marked regional variations were observed. The patients suffered from rhino conjunctivitis (55.7%), rhino-conjunctivitis plus asthma (31.6%) and asthma (12.7%). In monosensitised individuals, Parietaria was seen to be the main cause of the asthmatic syndrome (though our preliminary data also implicate Olea) followed by Gramineae. PMID- 1456408 TI - Horse chestnut (Aesculus hippocastanum) pollen: a frequent cause of allergic sensitization in urban children. AB - We investigated the incidence of allergic sensitization and the risk factors underlying sensitization in 214 urban children exposed to horse chestnut pollen. By means of the Phadezym RAST, we found IgE specific to horse chestnut pollen in 12.6% of the urban children, whereas it occurred in only 1.9% of control subjects recruited from a rural area. Reports of allergic symptoms in spring during the horse chestnut pollen load coincided with the presence of specific IgE in 5.1% of the urban group as against 1.4% of the recruited from the rural area. Environmental factors other than those related to urban living and higher horse chestnut pollen counts had no significant impact on allergic sensitization. Increased total IgE levels (greater than 100 kU/l), however, and the sensitization to pollen of other species significantly raised the odds for sensitization to chestnut pollen. They were highest in highly atopic children with sensitization to pollen, especially to that of plane trees (OR = 73.9). These results suggest the relevance of horse chestnut pollen because of the high allergic sensitization rate among urban children, and they should also be borne in mind when it comes to the planting of trees in urban areas. PMID- 1456409 TI - Does cutting of mugwort stands affect airborne pollen concentrations? AB - Pollen of mugwort (Artemisia vulgaris L.) is the most important allergenic pollen in urban areas of south and central Finland in late summer. The purpose of this study was to investigate, experimentally, whether the cutting of mugwort stands affects its airborne pollen concentrations. Experimental plots were either cut (4 plots) or uncut (4 plots) in 2 previous seasons: 4 of them were small (less than 0.5 hectare) and 4 large (greater than 5 hectares). Finally, the plots were divided randomly into 2 groups according to a third variable, cutting in the study season, 1989. Samples were taken on 2 rainless mornings at the peak mugwort flowering time. Two rotorod type samplers were used at heights of 1 and 2 m from ground level, simulating the inhalation heights of children and adults, respectively. The results indicate that cutting mugwort stands significantly reduces airborne pollen concentrations, but the treated areas have to be large, since in the town area there are plenty of mugwort pollen sources. The pollen concentrations at the 2 heights tested did not differ significantly. PMID- 1456410 TI - Cord blood IgE. I. IgE screening in 2814 newborn children. AB - Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). 48.6% of the sera contained less IgE than the detection limit 0.1 kU/l. Cord blood IgE values greater than or equal to 0.5 kU/l were regarded as elevated. 13.2% of the sera contained at least 0.5 kU/l of IgE, with a significant preponderance in boys. Geometric mean cord blood IgE was 0.13 kU/l and 0.12 kU/l, respectively. Geometric mean cord blood IgE was significantly higher in boys. A significant seasonal variation with lowest IgE values in the autumn was found. No correlation between cord blood IgE and birth weight or gestational age was demonstrated. Only few newborns had cord blood IgA values greater than 0.014 g/l, calculated as geometric mean cord blood IgA + 2 SD among children with no detectable cord blood IgE, indicating infrequent contamination with maternal blood. PMID- 1456411 TI - Cord blood IgE. II. Prediction of atopic disease. A follow-up at the age of 18 months. AB - Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). For follow-up we chose all infants with cord blood IgE greater than or equal to 0.5 kU/l and a randomly chosen group of the same size with cord blood IgE less than 0.5 kU/l. A total of 762 infants were clinically evaluated at 18 months of age. A diagnosis of definite atopy, probable atopy or no atopy, including both IgE and non-IgE mediated disease was established. Applying different cord blood IgE cut-off values (0.3, 0.5, 0.8, 1.1) we did not find an excess of atopic infants among those with elevated cord blood IgE irrespective of the chosen cut-off value. Atopic predisposition or family history of atopic disease was defined as at least one parent or older sibling with atopic disease. Significantly more infants with a family history developed atopy at 18 months. In the 2 series the positive predictive values of cord blood IgE greater than or equal to 0.5 were 43% and 46% and the sensitivities were 17% and 15%. The predictive values of having a family history were 48% and 44% and the sensitivities were 55% and 58%. PMID- 1456412 TI - Cord blood IgE. III. Prediction of IgE high-response and allergy. A follow-up at the age of 18 months. AB - Screening of total IgE in 2814 cord blood samples was analysed by Phadebas IgE PRIST in 2 1-year birth cohorts (1983-1984 and 1985-1986) in Denmark (n = 1189 + 1625). For follow-up we chose all infants with cord blood IgE greater than or equal to 0.5 kU/l and a randomly chosen group of the same size with cord blood IgE less than 0.5 kU/l. A total group of 762 infants were clinically evaluated at 18 months of age, and in 688 of these we evaluated total and specific IgE. A diagnosis of definite atopy, probable atopy or no atopy was established. In the present study we defined allergic disease as atopic disease combined with elevated total IgE. We found a statistically significant correlation between cord blood IgE and IgE at 18 months of age. Significantly more infants with elevated cord blood IgE had developed allergic disease at 18 months. A cut-off value of 0.3 kU/l for cord blood IgE was superior to the originally suggested 0.5 kU/l. Significantly more infants with elevated cord blood IgE had developed specific IgE antibodies at 18 months. The most frequent specific IgE antibody was towards cow's milk. Specific IgE antibodies were very rarely found when total IgE was not elevated. A total IgE at the age of 18 months greater than 26 kU/l could be regarded as elevated. With regard to allergic disease the positive predictive values of cord blood IgE greater than or equal to 0.3 kU/l in the 2 series were 21% and the corresponding sensitivities 67% and 46%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456413 TI - Quantification of pollen solute release using pollen grain column chromatography. AB - The impact of pollen on the respiratory mucosa was modeled by studying the process by which solutes are eluted from pollen grains. Rye grass (Lolium perenne), short ragweed (Ambrosia artemisiifolia), and white oak (Quercus alba) pollens were packed between glass wool plugs in small columns. Water was pumped through the columns and the eluate solute yield was determined by measurement of the dry solute weight. Solute separation was rapid, and concentrations and osmolalities of the eluate decreased exponentially. Theoretical initial solute concentrations were 179 g/l for rye grass, 55 g/l for short ragweed and 349 g/l for oak pollen eluates. Theoretical initial osmolarities of the same eluates were 321 mOsm/kg for rye grass, 196 mOsm/kg for ragweed and 424 mOsm/kg for oak pollen. Sequential separation of allergens (Lol p I, Amb a I, Amb a V), enzymes and proteins was demonstrated by specific assays. These observations suggest that the complex stimulus produced immediately after pollen grain hydration at the respiratory mucosal fluid interface is much more intense than previously envisioned. Sequential separation of pollen components has important implications for the production of improved allergenic extracts. PMID- 1456414 TI - The major allergen content of allergenic preparations reflect their biological activity. AB - The content of major allergens in biologically standardized allergenic preparations of birch, mite (Der p), cat, Alternaria (Alt a) and ragweed (Amb e) was determined. It was found fairly constant between species, i.e. varied within a factor of 2, with the exception of Alt a 1 in Alternaria alternata extract. This variation is allowed by authorities between different batches prepared from the same species of allergen. The method for biological standardization (BS) prescribed in the Nordic Guidelines has, for common inhalant allergens, been shown to give reproducible results between regions of Europe. However, it is difficult to define patients suitable for BS of most food allergens as well as less common inhalant allergens. Therefore we propose that, in the future, BS is replaced by determination of well-established major allergens and that 1 ng of major allergen is given the value of 1 Biological Unit. PMID- 1456415 TI - Age-dependency of sensitization to aero-allergens in asthmatics. AB - Skin reactivity (intracutaneous test) to histamine and allergens was studied cross-sectionally in a Dutch asthmatic patient population from childhood to old age (4-75 years). It was found that the histamine skin reactivity rose significantly (p less than 0.05) during childhood, was significantly higher in the 10-15-year age group, and was constant between 20 and 75 years of age. The mean wheal index (histamine ratio) of all allergens was constant during childhood, and decreased after the age of 25 for grass pollen and house-dust mite and after the age of 15 for the other allergens. The prevalence of a positive skin test decreased with age, except for grass pollen. During childhood the indoor allergens, cat dander and house-dust mite, were the most important, while after the age of 15 sensitivity to an outdoor allergen, grass pollen, increased markedly. At all ages house-dust mite was the most important allergen. After the age of 25 the prevalence of every allergen declines. The prevalence of a positive skin test to Cladosporium was unexpectedly high in childhood (10-40%). It can be concluded that the prevalence of a positive skin test declines with age, except for grass pollen. The degree of sensitization in asthmatics peaked in the age groups between 20 and 40 and sensitivity to indoor allergens developed earlier than sensitivity to outdoor allergens. PMID- 1456416 TI - Delayed hypersensitivity to 6-methyl-prednisolone in Henoch Schoenlein syndrome. AB - We report a case of allergic reaction to oral 6-methyl-prednisolone in a patient with Henoch Schoenlein syndrome. When this syndrome was first diagnosed the patient was started on 6-methyl-prednisolone orally and after 4 days he developed a pruriginous generalized maculo-papular eruption. The rash disappeared 1 week after withdrawal of 6-methyl-prednisolone. The skin tests performed 1 month after with main food allergens were negative. Patch test with 0.10 ml of solution containing 6-methyl-prednisolone 40 mg/ml was positive after 48 and 72 h. The cutaneous biopsy on the patch tested skin revealed a perivascular infiltrate of lymphocytes, histiocytes and eosinophils. PMID- 1456417 TI - Serum sickness-like syndrome associated with cefaclor therapy. AB - We describe 2 cases of paediatric patients who developed the main clinical features of a serum sickness reaction, while on treatment with cefaclor. A decrease in complement values was observed in both cases. Physicians should be aware of the possibility of such drug adverse reaction. PMID- 1456418 TI - Itchy dermatitis from Gynaikothrips ficorum March in a family group. AB - This study reports on the occurrence of an itchy dermatitis in all 4 adult members of a family, 2 men and 2 women, following infestation in the family environment with Gynaikothrips ficorum. The skin manifestations and the environmental study are described. PMID- 1456419 TI - Quantitation of proteins separated in N, N'-1,2-dihydroxyethylenebisacrylamide crosslinked polyacrylamide gels. AB - A simple and rapid method for the quantitation of proteins separated either by sodium dodecyl sulfate-electrophoresis or by isoelectric focusing in slab gels is presented. The method is based on the solubility of polyacrylamide gels crosslinked with N, N'-1, 2-dihydroxyethylenebisacrylamide (DHEBA) in periodic acid. After electrophoretic separation proteins are stained with Coomassie brilliant blue G-250. DHEBA gels show considerable swelling during the staining and destaining process but can be shrunk to their normal size in a 10% (w/v) solution of ammonium sulfate. Stained bands are cut from the gel and solubilized in periodic acid. During dissolution the dye decolorizes. Protein concentration in the solution is determined by a modified Coomassie dye-binding assay. Quantitation is linear in the range of 100 ng to 5 micrograms and not disturbed by dissolved gel. Separations in N, N'-1, 2-dihydroxyethylenebisacrylamide crosslinked gels show qualities similar to those in normal crosslinked gels. PMID- 1456420 TI - The direct hydrolysis of proteins containing tryptophan on polyvinylidene difluoride membranes by mercaptoethanesulfonic acid in the vapor phase. AB - A procedure for the amino acid analysis of polypeptides that contain tryptophan on polyvinylidene difluoride membranes is described. Lysozyme, carbonic anhydrase, phytochrome, and ovalbumin were tested. The protein, which was separated from others by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, was blotted from the gel onto a polyvinylidene difluoride membrane and directly hydrolyzed by 3 N mercaptoethanesulfonic acid vapor in a vacuum at 176 degrees C for 25 min. The hydrolysate was extracted with 0.1 N HCl and 30% methanol and used for amino acid analysis. The tested proteins were adequately hydrolyzed, and the recovery of tryptophan was very efficient. PMID- 1456421 TI - Direct purification of multiple ATF/E4TF3 polypeptides from HeLa cell crude nuclear extracts using DNA affinity latex particles. AB - We developed a method using affinity latex particles to rapidly and efficiently purify DNA-binding proteins directly from crude cell extracts. The particles are composed of a styrene core and a polyglycidyl methacrylate surface, to which DNA oligomers were immobilized by means of epoxy groups. Multiple polypeptides were copurified, which bound to the ATF/E4TF3-binding site from crude nuclear extracts of HeLa cells, within a few hours. Affinity-purified polypeptides stimulated transcription in vitro from a promoter in which ATF/E4TF3-binding sites were present. At least eight polypeptides with molecular masses of 116, 80, 65, 60, 55, 47, 45, and 43 kDa were copurified. About 2 micrograms of the 43-kDa protein was purified directly from 8 mg of crude nuclear extracts. All the polypeptides directly bound to the same DNA sequence and were thought to form a family. The results indicated that the particles are useful for quickly purifying various DNA binding proteins directly from crude cell extracts. PMID- 1456422 TI - Fluorimetric assay of D-lactate. AB - A fluorimetric assay for D-lactate in human blood samples was developed using an endpoint enzymatic assay with D-lactate dehydrogenase from Staphylococcus epidermidis. The intrabatch and interbatch coefficients of variance were 8.7% (n = 4) and 16.6% (n = 4), respectively. The limit of detection in blood was 3.73 nmol/ml. The assay suffers minor interference from S-D-lactoylglutathione, which was also present in the blood samples. The concentration of D-lactate in blood was (mean +/- SE, nmol/ml) normal healthy individuals, 11.0 +/- 1.2 (n = 7); and diabetic patients, 20.0 +/- 1.3 (n = 55) (a significant increase in diabetes mellitus; P < 0.01, Mann-Whitney U test). PMID- 1456423 TI - Spectrofluorometric estimation of intermediates of chlorophyll biosynthesis: protoporphyrin IX, Mg-protoporphyrin, and protochlorophyllide. AB - A highly sensitive spectrofluorometric method for quantitative estimation of certain precursors of chlorophyll biosynthesis from the mixtures of plant tetrapyrroles having overlapping fluorescence emission spectra is developed. At room temperature (293 degrees K) protoporphyrin IX is monitored from its emission maximum, 633 nm, when excited at 400 nm (E400/F633). Protochlorophyllide is estimated at 638 nm, while being excited at 440 nm (E440/F638). Mg protoporphyrin+Mg-protoporphyrin monoester pool has emission around 589-592 nm. Therefore the integration value of the emission band that extends from 580 to 610 nm is taken to calibrate its concentration. This spectrofluorometric method designed for the determination of protoporphyrin IX, esterified and nonesterified Mg-protoporphyrin pool, and protochlorophyllide is far superior to available spectrophotometric methods and estimates as low as 1 nM concentration of plant pigments. As minute quantities of individual pigments can be quantitatively analyzed from their mixtures, this method eliminates analytical uncertainties due to recovery losses caused by chromatography. However, only dilute samples can be estimated by this spectrofluorometric method as the quantitative relation between fluorescence and concentration deviates from linearity at high, i.e., above 150 nM, concentrations of pigment to be quantified. PMID- 1456424 TI - Changes in the redox distribution of rat liver by ischemia. AB - The changes in the redox distribution of the ischemic rat liver were studied using the redox scanner, which is a time-sharing, tissue fluorescence and reflectance spectroscopy with fine spatial resolution, with the results presented as a histogram and a gray-scaled picture. Hepatic inflow was clamped for 10 min (group 1), 20 min (group 2), and 30 min (group 3). The ratio of oxidized flavoprotein to reduced pyridine nucleotide fluorescence (FP/PN), representing the intracellular redox state, and hemoglobin reflectance were measured prior to clamping and at subsequent times following declamping in each group. The mean and the range width of FP/PN histogram decreased with the prolongation of ischemic time. In group 1, FP/PN histogram showed a remarkably wide range at 2 min after declamping but was almost completely recovered to preischemic levels at 10 min after declamping. In contrast, in groups 2 and 3, the mean of FP/PN histogram was only partially recovered at 10 min after declamping and the range width continued to increase. The correlation between FP/PN fluorescence and hemoglobin reflectance pictures suggested that the local stagnation of blood flow caused tissue hypoxia, preventing the recovery of the redox state probably in the centrilobular area. PMID- 1456425 TI - A turbidimetric assay of lipid transfer activity. AB - A novel method to assay insect plasma lipid transfer particle (LTP) activity has been developed that employs insect high density lipophorin (HDLp) and human low density lipoprotein (LDL) as donor/acceptor substrate particles. At a 3:1 or greater HDLp:LDL protein ratio, LTP-mediated net vectorial transfer of diacylglycerol from lipophorin to LDL produces destabilized LDL particles that aggregate, causing sample turbidity. Turbidity was measured spectrophotometrically as a function of absorbance at 340 nm. After an initial lag phase, lipoprotein sample turbidity increased as a function of reaction time and LTP concentration. Saturation was observed at longer times or higher LTP concentrations, indicating that a reaction end point had been reached. As the substrate HDLp concentration was increased relative to LDL, a saturable increase in LTP-induced lipoprotein sample turbidity was observed. When the LDL concentration was increased relative to HDLp, however, there was an initial production of turbidity but at higher concentrations the sample did not develop turbidity. Reaction progress was also dependent on temperature over the range 0 37 degrees C. Taken together the results are consistent with the concept that LTP mediated diacylglycerol transfer from HDLp to LDL creates unstable product LDL particles that aggregate. The assay method is advantageous because it employs relatively abundant, natural lipoprotein substrates, does not require prelabeling of donor lipid particles with radioactive or fluorescent lipids, and does not require separation of donor and acceptor after incubation. This is the first description of a lipid transfer assay that can be measured spectrophotometrically. PMID- 1456426 TI - Purification of mucin glycoproteins by density gradient centrifugation in cesium trifluoroacetate. AB - A procedure for the rapid isolation of mucin glycoprotein by density gradient centrifugation in cesium trifluoroacetate (CsTFA) is described. The separation of mixtures of rat tracheobronchial mucin, DNA, hyaluronic acid, and bovine serum albumin in CsTFA gradients was superior to that in cesium bromide gradients. Inclusion of guanidinium chloride or urea in the gradient had no influence on the separation obtained. The mucins isolated from sputum samples of cystic fibrosis patients by this procedure are largely free of nucleic acid, nonglycosylated proteins, and glycosaminoglycans. The results of the use of CsTFA gradient centrifugation for the isolation of mucin from extracts of bovine submaxillary gland are also presented. The CsTFA method is particularly suitable for the high yield isolation of mucin from individual samples which are available in limited quantities. PMID- 1456427 TI - Isolation of peroxisomes from frozen human liver samples. AB - This paper shows the successful isolation of peroxisomes from human liver samples that were kept frozen at -70 degrees C. Purification of these peroxisomes was obtained by a combination of two subcellular fractionation techniques: differential centrifugation and isopycnic fractionation in Nycodenz density gradients. Peroxisome integrity was evaluated by latency measurements and by ultrastructural observation. The procedure described here may be useful for the isolation of other subcellular organelles from frozen human samples. PMID- 1456428 TI - High-performance liquid chromatographic determination of N-epsilon-(2 propenal)lysine in biological samples after derivatization with diethylethoxymethylenemalonate. AB - A recently reported methodology for amino acid analysis by HPLC has been adapted for quantification of N-epsilon-(2-propenal)lysine (a modified lysine by reaction with malondialdehyde that has been found in enzymatic digests of foods and in urine) in biological samples. We describe its use for investigating the in vitro degradation of N-epsilon-(2-propenal)lysine using rat tissue homogenates. Lysine dipeptide, used as a control in the incubation mixtures, and the lysine released by the hydrolytic action of the homogenates in the in vitro incubations are quantified in the same way. The samples are subjected to a cleanup prederivatization step using PD-10 disposable columns (Pharmacia). This allows precolumn derivatization with diethylethoxymethylenemalonate (50 min, 50 degrees C) and resolution of the derivatives of the compounds of interest by reversed phase HPLC (binary gradient, 45 min) with quantification based on the uv absorption of the derivatives at 280 nm (detection limits below 1 pmol). The entire analysis takes 110 min. This method can be of general use for the determination of N-epsilon-(2-propenal)lysine in the context of research dealing with protein deterioration by reaction with malondialdehyde in biological systems and in foods. A method for the synthesis of N-epsilon-(2-propenal)lysine, used as external standard for the HPLC analysis, is described. PMID- 1456429 TI - Latex-based thin-layer immunoaffinity chromatography for quantitation of protein analytes. AB - A rapid immunochromatographic method for qualitative and quantitative analysis of protein antigens is described. The method is based on the "sandwich" assay format using monoclonal antibodies (Mabs) of two distinct specificities. Mabs of one specificity are covalently immobilized to a defined detection zone on a porous membrane while Mabs of the other specificity are covalently coupled to blue latex particles which serve as a label. The sample is mixed with the Mab-coated particles and allowed to react. The mixture is then passed along a porous membrane by capillary action past the Mabs in the detection zone, which will bind the particles which have antigen bound to their surface, giving a blue color within this detection zone with an intensity logarithmetrically proportional to the antigen concentration in the sample. Analysis is complete in less than 10 min, requires a minimum amount of sample (4 microliters), and has a detection limit below the nanomolar range for the antigen we studied, human chorionic gonadotropin. PMID- 1456430 TI - The assay of methylglyoxal in biological systems by derivatization with 1,2 diamino-4,5-dimethoxybenzene. AB - A procedure for the assay of methylglyoxal in biological systems is described, together with sample storage, sample processing procedures, and statistical evaluation. Specimen data are presented. Methylglyoxal was assayed by derivatization with 1,2-diamino-4,5-dimethoxybenzene and high-performance liquid chromatography (HPLC) of the resulting quinoxaline, 6,7-dimethoxy-2 methylquinoxaline, with spectrophotometric or fluorescence detection. Derivatization, solid-phase extraction, and HPLC were performed under acid conditions to prevent the spontaneous formation of methylglyoxal from glyceraldehyde 3-phosphate and dihydroxyacetone phosphate during the assay. The limits of detection in the biological matrix were 45 pmol (absorbance detection) and 10 pmol (fluorimetric detection), the recovery was 58%, and the intra- and interbatch coefficients of variance were 7.7 and 30.0%, respectively. The concentration of methylglyoxal in whole blood from normal healthy human individuals was (mean +/- SE, nM) 256 +/- 92 (n = 12) and that from diabetic patients was 479 +/- 49 (n = 55), showing a significant increase in diabetes mellitus (P < 0.01; Mann-Whitney U test). Sample processing under acidic conditions was essential to avoid interferences. Previous estimates of the concentration of methylglyoxal in biological samples require re-evaluation. PMID- 1456431 TI - Quantitation of deoxyribonucleoside 5'-triphosphates by a sequential boronate and anion-exchange high-pressure liquid chromatographic procedure. AB - A rapid method for the quantitative determination of cellular deoxyribonucleoside 5'-triphosphates is described. Cell extracts are first separated by boronate chromatography at pH 8.9, which removes 99% of the ribonucleoside triphosphate (rNTPs) from the deoxyribonucleoside triphosphates (dNTPs). The resulting dNTP fraction is analyzed by gradient high-pressure liquid chromatography utilizing a strong anion-exchange column, which can separate minor rNTP peaks from the corresponding dNTPs. This sequential procedure, which requires less than 1 h per sample for both chromatographic steps, results in the quantitative recovery of greater than 98% of the dNTPs from cell extracts. Nucleotide analogs, such as 1 beta-D-arabinofuranosylcytosine-5'-triphosphate and 5-bromo-2'-deoxyuridine-5' triphosphate, can also be quantitated efficiently by this method. PMID- 1456432 TI - Localization of in vivo ribosome pause sites. AB - A protocol for the localization of the 5' boundaries of in vivo ribosomal pausing sites has been developed. These mapping experiments combine two basic techniques. The first is the isolation of polysomal transcripts via centrifugation of tissue extracts through a sucrose cushion in the presence of translational elongation inhibitors. The second technique involves a micrococcal nuclease protection assay first developed by Wolin and Walter for in vitro-bound ribosomes (EMBO J. 7, 3559 3569, 1988). Using this method, the 5' boundaries of in vivo ribosomal pause sites were localized on spinach chloroplast mRNAs derived from the atpA gene. This method is easily adaptable to the identification of in vivo ribosomal pause sites from any organism. It could also be adapted to the localization of in vivo binding sites for other nucleic acid binding proteins. PMID- 1456434 TI - Analysis of variance of parameter estimates: F tests and t tests. AB - The problem of comparing and pooling experimentally independent estimates of a parameter such as a Michaelis constant (K) has been treated as a simple analysis of variance of "within" and "between" set deviations from the fitted variable (v). As applied to assessing the reproducibility of multiple estimates of the same K, this is identical to the procedure of Duggleby (Anal. Biochem. 189, 84 87, 1990). However, the theory developed here shows that applying Duggleby's procedure to the comparison of two experiments (each consisting of multiple data sets) depends critically on the assumption of equal errors within and between the individual sets, i.e., Fvb vw = s2wv/s2bv is close to 1. Application of the method when this is not the case will underestimate the common error (s2rv), overestimate its associated degrees of freedom (vr = vb+vw), and may suggest apparently significant differences where there are none. The theory also shows that this situation is an instance of the Fisher-Behrens problem and shows how Welch's solution can be applied. This gives the between set error s2bv as the corrected estimate of the common error and the corrected degrees of freedom as a simple function of vb, vw, and Fvb vw. When the nine prephenate dehydratase data sets which originally showed three apparently significant differences were reanalyzed in this way, all the variations in K were found to be within the range of the experimental error. PMID- 1456433 TI - Determination of transcription factor isoelectric point by two-dimensional native isoelectric focusing and electrophoretic mobility shift analysis. AB - A rapid, sensitive, and inexpensive assay is described for the determination of isoelectric points of native transcription factors derived from cell nuclei. This assay depends on a transcription factors' ability to bind DNA with high specificity and obviates the need for specific antisera or additional detection methods in identifying a particular protein following isoelectric focusing. This method has been applied to two ubiquitous proteins, the octamer transcription factor, Oct-1, and the multisubunit CCAAT box factor, NF-Y. Isoelectric points have been determined under native conditions using conventional isoelectric focusing in the first dimension, followed by binding to a specific oligonucleotide DNA probe, and separation of specific DNA/protein complexes from unbound DNA in the second dimension using native polyacrylamide gel electrophoresis. Oct-1 from HeLa cell nuclei was shown to have a pI of 9.6, while NF-Y was shown to have a pI of 4.5. This method is applicable to any transcription factor which binds DNA specifically and may be used to identify changes in surface charge characteristics which occur as a result of alternative splicing events and/or following transcription factor post-translational modification(s). PMID- 1456435 TI - Reusable cDNA libraries coupled to magnetic beads. PMID- 1456436 TI - Purification of A14-tyrosyl [125I]iodoinsulin using C18 reverse-phase cartridges. PMID- 1456437 TI - An easy microtiter plate-based chromogenic assay for ethylenediaminetetraacetic acid and similar chelating agents in biochemical samples. PMID- 1456438 TI - Rapid filtration assays for protein kinase C activity and phorbol ester binding using multiwell plates with fitted filtration discs. AB - In the conventional approach protein kinase activity and phorbol ester binding associated with protein kinase C (PKC) are measured by initially incubating samples in either test tubes or multiwell plates, followed by filtration of the terminated reaction mixture using either a manifold filtration device or a cell harvester. Here we report a method in which both the incubations and filtrations necessary for the determination of either protein kinase activity or phorbol ester binding are carried out in the same multiwell plate with fitted filtration discs made of polyvinylidene difluoride (Durapore membrane). Due to the very low binding of protein to these filters, there is no interference caused by these filters during the incubation period of the assays. The drawback with these filters compared to commonly used cellulose acetate membrane filters is that they retain less of the phosphate acceptor substrate histone H1 (only 15%) if filtered and washed with standard 5% trichloroacetic acid. However, this can be overcome by increasing the trichloroacetic acid concentration to 25% during filtration. For phorbol ester binding determinations, the samples are incubated with [3H]phorbol 12,13-dibutyrate in the microwells, the ligand bound PKC is adsorbed onto DEAE-Sephadex beads, and the beads then are filtered and washed in the same microwells. Furthermore, this multiwell filtration approach can also be adopted to previously described cytosolic phorbol ester receptor assays, which have the broader conditions for optimal binding to receptors. Durapore membrane filters are found to work well for punching into scintillation vials and there is complete recovery of the radioactivity retained with the filters. In the protein kinase assay the background radioactivity is very low (< 200 cpm) and in the phorbol ester binding assay the nonspecific binding is less than 1%. Thus, these low background values result in at least a fourfold increase in sensitivity for these assays. Since the incubations and filtrations are carried out in the same well without any transfer of the sample, the coefficient of variation in multiple determinations is found to be low. Furthermore, this method is rapid and more convenient for analyzing a larger number of samples than conventional methods which use test tubes, and it is less expensive to set up compared to the automated methods that use a cell harvester. PMID- 1456439 TI - Detection of hepatitis B virus DNA in human serum samples: use of digoxigenin labeled oligonucleotides as modified primers for the polymerase chain reaction. AB - Nonradioactive techniques have been used for the direct detection of hepatitis B virus DNA in human serum samples. A comparison of two different systems using digoxigenin-labeled DNA probes is presented. Furthermore, oligonucleotides containing one molecule of the hapten digoxigenin at the 5'-end were prepared and used as primers for the polymerase chain reaction. Amplified DNA can be directly analyzed with anti-digoxigenin Fab fragments labeled with alkaline phosphatase and chemiluminescent substrates. PMID- 1456440 TI - Trans-diamminedichlorplatinum (II)-modified probes for detection of picogram quantities of DNA. AB - A novel simple nonradioactive method for detection of specific nucleotide sequences has been developed. This method consists of the hybridization of a target DNA with a DNA probe modified with trans-diamminedichlorplatinum(II) (trans-DDP) followed by detection of DNA/DNA hybrids with affinity-isolated anti DNA-trans-DDP antibodies and poly-horseradish peroxidase-protein A conjugate. Major advantages of this approach are the low cost and the extreme simplicity of the labeling procedure, which involves only mixing of the reagents. The sensitivity of the proposed technique is sufficient to detect 0.8 pg of DNA in Southern blot hybridization and 25 fg in dot hybridization and permits colony screening. PMID- 1456441 TI - N-glycosylation site mapping of human serotransferrin by serial lectin affinity chromatography, fast atom bombardment-mass spectrometry, and 1H nuclear magnetic resonance spectroscopy. AB - This report describes the N-glycosylation site mapping of human serotransferrin (h-STF). Reduced and S-carboxymethylated h-STF was digested with trypsin or chymotrypsin. Glycopeptides in the proteolytic digests were isolated by serial concanavalin A (Con A), Sambucus nigra agglutinin (SNA), and Phaseolus vulgaris leukoagglutinin (LPHA) affinity chromatography and subjected to preliminary analysis by 1H NMR spectroscopy. The glycopeptide fractions were then individually digested with N-glycanase. One part of the digest of each fraction was analyzed by fast atom bombardment-mass spectrometry (FAB-MS) to identify the peptide sequences of the glycosylation sites. The other part was used to isolate the oligosaccharide by the corresponding lectin affinity chromatography and to characterize the structures of the isolated oligosaccharides by 1H NMR spectroscopy and FAB-MS. The oligosaccharides in the Con A-bound fraction were shown to have bi-alpha(2-->6)-sialyl, diantennary structures. The SNA-bound fraction was shown to contain trisialyl, triantennary structures. Di- and triantennary oligosaccharides were found to occur on each of the two N glycosylation sites of h-STF (Asn413 and Asn611) in the ratio of approximately 85:15. The SNA-bound glycopeptides were further fractionated by LPHA affinity chromatography. Two different oligosaccharides were characterized, namely, a trisialyl 2,4-triantennary and a trisialyl 2,6-triantennary glycan. The ratio of 2,4-triantennary vs 2,6-triantennary oligosaccharides attached to glycosylation site Asn413 was found to be approximately 5:1, whereas the two isomeric triantennary oligosaccharides were found to be attached to glycosylation site Asn611 in the ratio approximately 1:1. PMID- 1456442 TI - An aluminum silicate binding assay for quantitation of degradation of cholecystokinin octapeptide and other short peptides. AB - Most available techniques for the quantitation of enzymatic degradation of peptide hormones are time-consuming and require expensive equipment and/or novel reagents. Our aim here was to develop a rapid and sensitive assay for the measurement of degradation of cholecystokinin octapeptide (CCK-8) as well as other short, hydrophobic peptides. The proposed technique is based on our novel observation that intact CCK-8, but not its degradation product(s), binds to Lloyd reagent, a form of aluminum silicate. When radiolabeled CCK-8 was exposed to rat liver cytosol containing endogenous CCK-degrading activity, there was a time dependent decrease in the binding of radiolabel to aluminum silicate [from 86 to 8% over 60 min at 37 degrees C]. The decrease in binding closely paralleled the extent of CCK-8 degradation over time as assessed by high-performance liquid chromatography and immunoprecipitation with specific polyclonal antibodies to CCK 8. While aluminum silicate did not efficiently bind to C-terminal and N-terminal CCK tetrapeptides, magnesium silicate bound to both tetrapeptides (> 82%), but not to their radiolabeled degradation products. Both aluminum and magnesium silicate also extensively bound (> 82%) to other peptide hormones including Met enkephalin, somatostatin, and secretin, but did not bind their degradation products. These binding assays will be useful in studies of peptidases which degrade cholecystokinin or other small, hydrophobic peptides. PMID- 1456443 TI - Platelet dense granule release reaction monitored by high-performance liquid chromatography-fluorometric determination of endogenous serotonin. AB - The platelet dense granule release reaction was monitored by measuring the serotonin content of platelets collected by filtration following release. Sensitive HPLC-fluorometric analysis permitted release to be assessed using small (25-50 microliters) volumes of plasma and whole blood. Release could be examined for periods as short as 1 s due to the rapid stoppage effected by filtration. The half-life of thrombin-stimulated (1 U/ml) release was 2-3 s, the EC50 values observed for thrombin-stimulated release over a 60-s release period were 0.01 0.03 U/ml for diluted whole blood and plasma samples. PMID- 1456444 TI - A perifusion system for cultured hepatocytes. AB - A perifusion system for primary cultures of hepatocytes is described. The system accommodates 20 rotated petri dishes (60 mm) and allows individual medium composition and sampling for each dish. Cell number and insulin (15 pM to 7.7 nM) were stable in the system for at least 24 h. The dose-response relationship for induction by insulin of glucokinase and pyruvate kinase was shifted to the left by a factor of 9 and 5, respectively, as compared to conventional, stationary cultures. The system is useful for studies at low and/or constant concentrations of substrates, hormones, growth factors, etc., with monolayers of cells having a high metabolic capacity. PMID- 1456445 TI - Radioiodination of the active site of tissue plasminogen activator: a method for radiolabeling serine proteases with tyrosylprolylarginyl chloromethyl ketone. AB - Tyrosylprolylarginyl chloromethyl ketone (YPRck) is a radioiodinatable inhibitor that irreversibly binds the active site of tissue plasminogen activator (tPA). A two-step reaction is employed where (1) the YPRck reagent is iodinated and (2) the 125I-YPRck is reacted with the tPA sample; therefore the oxidative effects of conventional protein iodination are avoided. Using fibrin binding as a probe of native tPA binding function, YPRck labeling was shown to be superior to other types of surface iodination. 125I-YPRck was prepared at a high specific radioactivity; i.e., one 125I per 3.5 molecules of peptidyl chloromethyl ketone. Labeled YPRck formed a one to one covalent, sodium dodecyl sulfate stable, complex with tPA resulting in a preparation of 10 mCi per milligram protein, which corresponded to an incorporation ratio of 1:3.5 (125I-YPRck:tPA). Both one chain and two-chain forms of tPA reacted with YPRck. Radiolabeling tPA with 125I YPRck occurred in a time-dependent manner with half-maximal incorporation at approximately 30 min under the conditions employed in these studies. The pH optimum for the reaction of tPA with 125I-YPRck was 7.4. Solutions of tPA at less than 1 microgram/ml were efficiently labeled with 125I-YPRck, thus allowing the quantitation of functional protease by incorporation of radiolabel. Significantly, 125I-YPRck specifically labeled tPA in cell culture supernatants after transient transfection of cells with plasmid DNA containing the gene for tPA. Other serine proteases were tested for their relative reactivity with 125I YPRck. Thrombin and Factor Xa incorporated 125I-YPRck to higher levels than two chain tPA; whereas plasmin, urokinase, and other plasma proteases were not as efficiently radiolabeled. The use of 125I-YPRck allows rapid and specific radiolabeling of a large number of tPA samples in a nondenaturing environment with a known localization of the radiolabeling reagent. PMID- 1456446 TI - Isoelectric focusing by free solution capillary electrophoresis. AB - A reproducible, quantitative isoelectric focusing method using capillary electrophoresis that exhibits high resolution and linearity over a wide pH gradient was developed. RNase T1 and RNase ba are two proteins that have isoelectric points (pI's) at the two extremes of a pH 3-10 gradient. Site directed mutants of the former were separated from the wild-type form and pI's determined in the same experiment. The pI's of RNase T1 wild-type, its three mutants, and RNase ba were determined for the first time as 2.9, 3.1, 3.1, 3.3, and 9.0, respectively. The paper describes the protocol for isoelectric focusing by capillary electrophoresis, as well as presenting data describing the linearity, resolution, limits of mass loading, and reproducibility of the method. PMID- 1456447 TI - Uracil DNA glycosylase-mediated cloning of polymerase chain reaction-amplified DNA: application to genomic and cDNA cloning. AB - A simple and rapid method for cloning of amplification products directly from the polymerase chain reaction (PCR) has been developed. The method is based on the addition of a 12-base dUMP-containing sequence (CUACUACUACUA) to the 5' end of PCR primers. Incorporation of these primers during PCR results in the selective placement of dUMP residues into the 5' end of amplification products. Selective degradation of the dUMP residues in the PCR products with uracil DNA glycosylase (UDG) disrupts base pairing at the termini and generates 3' overhangs. Annealing of 3' protruding termini to vector DNA containing complementary 3' ends results in chimeric molecules which can be transformed, with high efficiency, without in vitro ligation. Directional cloning of PCR products has also been accomplished by incorporating different dU-containing sequences at the end of each PCR primer. Substitution of all dT residues in PCR primers with dU eliminates cloning of aberrant "primer dimer" products and enriches cloning of genuine PCR products. The method has been applied to cloning of inter-Alu DNA sequences from human placental DNA. Using a single primer, DNA sequences between appropriately oriented Alu sequences were amplified and cloned. Cloning of cDNA for the glyceraldehyde-3'-phosphate dehydrogenase gene from rat brain RNA was also demonstrated. The 3' end region of this gene was amplified by the 3' RACE method and the amplified DNA was cloned after UDG digestion. Characterization of cloned DNAs by sequence analysis showed accurate repair of the cloning junctions. The ligase-free cloning method with UDG should prove to be a widely applicable procedure for rapid cloning of PCR-amplified DNA. PMID- 1456448 TI - Determination of monosaccharides and sugar alcohols in tissues from diabetic rats by high-performance liquid chromatography with pulsed amperometric detection. AB - A sensitive and simple high-performance liquid chromatographic method has been developed to determine the concentration of monosaccharides and sugar alcohols in animal tissues. Five neutral monosaccharides (D-glucose, D-galactose, D-mannose, D-fructose, and D-ribose) and three neutral sugar alcohols (myo-inositol, glycerol, and D-sorbitol) predominate in the renal cortices and sciatic nerves of rats. These monosaccharides and sugar alcohols were extracted with distilled water, purified by deproteinization with ethanol, a Sep-Pak C18 cartridge, and columns of Dowex 50W-X8 and Amberlite CG-400, then separated on Ca2+ and Pb2+ cation-exchange columns, eluted with deionized distilled water at 80 degrees C, and detected using integrated pulsed amperometry. About 10 pmol of each sugar was detectable with a signal-to-noise ratio of 10:1. D-Glucose, D-fructose, D sorbitol, and D-mannose were higher in both the renal and sciatic tissues of diabetic rats than in those of normal animals. D-Ribose and glycerol were higher in the renal cortex of diabetic animals. PMID- 1456449 TI - Evidence for the glyoxylate cycle in human liver. AB - The enzymatic activities unique to the glyoxylate cycle of higher plants and certain lower invertebrates, isocitrate lyase and malate synthase, have been demonstrated in homogenates prepared from human liver. Human liver can also carry out cyanide-insensitive fatty acid oxidation from palmitate. Utilizing light microscopic immunocytochemistry with an antibody produced against Euglena malate synthase, this enzyme localizes in numerous ovoid granules in human hepatocytes. Also, immunocytochemistry using antibodies produced against rat fatty acyl-CoA oxidase showed that this enzyme was localized in similar structures. With routine cytochemistry, catalase was seen in identical granular bodies. Both catalase and fatty acyl-CoA oxidase are peroxisomal enzymes. The presence of malate synthase in liver homogenates was further confirmed by Western blot analysis. These data suggest that the human liver may be capable of utilizing the carbon backbone of fatty acids for carbohydrate synthesis since the glyoxylate cycle in lower organisms subserves this anabolic function. PMID- 1456450 TI - Changes of cytochemical properties in the Golgi apparatus during in vivo differentiation of the ameloblast in developing rat molar tooth germs. AB - The cytochemical changes of the Golgi stacks occurring concomitantly with cell differentiation were examined in ameloblasts of developing rat molar tooth germs using osmium impregnation and cytochemistry with nicotinamide adenine dinucleotide phosphatase (NADPase), thiamine pyrophosphatase (TPPase), and acid phosphatase (Acpase). NADPase, TPPase, and Acpase activities were already present in the Golgi stacks of the inner enamel epithelial cells, the undifferentiated form of the ameloblast: NADPase activity existed in the medial Golgi cisternae, TPPase activity in the trans Golgi cisternae, and Acpase activity in almost all cisternae and strongly in the trans-most cisterna of the Golgi stack. At this stage, however, osmium deposits after impregnation were not observed in the cisterna of Golgi stacks but were present in some small vesicles. These vesicles were located throughout the cytoplasm. Osmiophilic cisternae in the Golgi stacks were apparent for the first time at the stage when the Golgi apparatus developed and migrated to the region distal to the nucleus with the progression of cell differentiation. These findings indicate that the cis subcompartment of the Golgi apparatus was incomplete in the inner enamel epithelial cells with regard to appearance of its cytochemical property, as compared with the medial and trans subcompartments. It is suggested that the cis compartment of the Golgi stack may be completed only in the last stage of the compartmentalized Golgi organization during differentiation of the ameloblast. PMID- 1456451 TI - High-resolution immunolocalization of osteopontin and osteocalcin in bone and cartilage during endochondral ossification in the chicken tibia. AB - The ultrastructural distribution of two noncollagenous proteins, osteopontin (OPN) and osteocalcin (OC), originally extracted from bone matrix and proposed to play an important role in bone formation, was examined in the matrices of bone and cartilage from embryonic and postnatal chicken tibial growth plates by high resolution immunocytochemistry using the colloidal gold technique. In bone, immunolabeling patterns using polyclonal antibodies against chicken OPN and OC were generally similar in that both showed an intense, but regionally variable, labeling of mineralized bone matrix and small mineralization loci dispersed throughout the osteoid and containing prominent condensed organic material. Unmineralized osteoid showed weak-to-moderate labeling. In the mineralized bone matrix proper, labeling was predominantly associated with amorphous, electron dense patches of organic material among the collagen fibrils. In growth plate cartilage, both proteins first appeared related to calcified cartilage in the hypertrophic zone, although the labeling patterns were somewhat different. For OPN, gold particles were mostly associated with an organic lamina limitans-like density containing condensed, filamentous organic matrix at the periphery of small nodules and large masses of calcified cartilage, with additional moderate labeling throughout the interior of the calcified cartilage. For OC, labeling was observed over filamentous structures throughout the calcified cartilage matrix, with some, but less, labeling at the periphery. In the lowermost zones of the growth plate, the major reaction using both antibodies was found over a layer of dense, amorphous organic material at the periphery of the calcified cartilage at the future bone/calcified cartilage interface, a labeling pattern that persisted following bone deposition at these sites. OPN and to a lesser extent OC were also concentrated in cement (resting, reversal) lines. Throughout the bone and cartilage of the tibia, cells of both the osteoblastic and the osteoclastic lineages were found directly apposed to labeled surfaces and lamina limitans of organic matrix containing OPN and OC. In summary, it is concluded from the immunocytochemical data presented here that the association of OPN and OC with mineralized regions of the extracellular matrices of bone and cartilage and the accumulation of these proteins at tissue surfaces and interfaces are consistent with the hypotheses that they play a role in the extracellular mineralization process per se and/or that they may mediate cell adhesion and dynamics. PMID- 1456452 TI - Ultrastructural alteration of cartilaginous fibril arrangement in the rat mandibular condyle as revealed by high-resolution scanning electron microscopy. AB - Three-dimensional alteration of fibrillar matrix in the rat mandibular condylar cartilage was investigated with a high-resolution scanning electron microscope (SEM) and it was determined whether alterations correlate with developing occlusion and advancing age. Two important SEM techniques of DMSO freeze-cracking and treatment with trypsin and hyaluronidase were employed to remove interfibrillar proteoglycans and disclose fibril arrangement. Our SEM investigation demonstrated that collagen fibrils in the fibrous zone covering hyaline-cartilaginous area in the condyle are thicker (50 to 80 nm in diameter) than the fibrils (30 to 50 nm in diameter) that predominantly constituted an interterritorial fibrillar matrix (IFM) in the area. While the thick fibrils had a distinct striation of about 55 nm periodicity, the thin fibrils had no distinguishable striation. The thick fibrils having a periodic striation of about 60 nm was found along with the thin fibrils, also in the IFM in the aged rats and in the deep IFM, but were considerably less than the thin fibrils. The fibrils in the fibrous zone and IFM were disorderly arranged at 19-day-insemination age. In 1-week-old rats whose incisors erupted, the fibrils constituting the fibrous zone altered from disordered to ordered arrangement. The IFM in these rats took the form of a network. Incorporation of small fibrillar bundles into the fibrillar network was seen in 2-week-old rats whose upper and lower first molars erupted. In 8-week-old rats whose molars had erupted completely, the IFM completely occupied by regularly oriented fibrils appeared additionally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456453 TI - Architectural design, fiber-type composition, and innervation of the rat rectus abdominis muscle. AB - The rectus abdominis muscle is architecturally compartmentalized by tendinous intersections and is supplied by multiple thoracic nerves. In this study, the rectus abdominis of the rat has been qualitatively and quantitatively examined with regard to muscle dimensions, fiber organization, fiber-type composition, and innervation. The muscle exhibits architectural heterogeneity and different patterns of innervation among its thoracic, epigastric, and hypogastric parts. The epigastric part, adherent to the rectus sheath via tendinous intersections, represents relatively simple design. It is formed by serially arranged compartments with shorter fibers, compared with the other parts. These compartments are segmentally supplied by thoracic nerves. The hypogastric part is more complex, forms an interdigitation of muscular slips, and has segmental distribution of thoracic nerves in mediolateral direction. The thoracic part much differs from the other parts. It has smaller cross-sectional areas, compartments composed of abundant nonspanning fibers with intrafascicular termination, and non segmental distribution of thoracic nerves. In addition to these craniocaudal specializations among the three parts, the muscle exhibits mediolateral differences in fiber-type composition. Slow-twitch oxidative fibers are more densely distributed in the medial half region than the lateral, whereas fast twitch glycolytic fibers follow an inverse pattern. The mediolateral differences in fiber-type composition as well as the craniocaudal specializations in architectural design and innervation imply regionally differentiated recruitments of the muscle in various behaviors. PMID- 1456454 TI - Structural response of the hamster Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study. AB - Reproductively active hamsters were hypophysectomized and examined 6 or 20 days later in a combined morphometric and endocrine study of the Sertoli cell to determine 1) the morphological and endocrine effects of hypophysectomy of both short- and long-term duration, 2) if regression of Sertoli cells after hypophysectomy in a seasonal breeder resembles regression due to seasonal changes, and 3) if effects of hypophysectomy in a seasonal breeder are equivalent to the effects of hypophysectomy in a nonseasonal breeder. Six days after hypophysectomy, at a period when germ cell degeneration is first noted, there was a significant decrease in testis weight, interstitial space, tubule diameter and length, volume of seminiferous tubule, and tubular lumen. There were no significant changes in Sertoli cell nuclear and cytoplasmic volume although cell surface area was decreased significantly. Most organelles exhibited no significant change in volume or surface area except for secondary lysosomes which expectedly increased in volume as the result of phagocytosis of germinal cells. Thus at an early time period when functional changes in germ cells and Leydig cells are clearly evident (Russell et al. [1992] Endocrinology), the Sertoli cell shows minimal changes. Twenty days after hypophysectomy, the cell, nuclear and cytoplasmic volumes and surface area of the Sertoli cells, and volumes and surface areas of nearly all organelles were significantly decreased from values measured in normal and in short-term hypophysectomized hamsters. The exceptions were the total volumes of lipid which increased significantly and lysosomes which were similar to normal but significantly lower than short-term hypophysectomized animals. The long-term hypophysectomized hamster Sertoli cell, like that of the short-day hamster (Sinha Hikim et al. [1989b] Endocrinology, 125:1829-1843) is structurally regressed as a whole rather than exhibiting selective decreases in cellular and subcellular components. The size of the Sertoli cell in pituitary intact, long- and short-term hypophysectomized animals showed positive and significant correlations with the volumes and surface areas of all its cytoplasmic organelles except the volume of lipid which showed a negative, significant correlation. Comparisons of long-term hypophysectomized hamsters (in long-day light exposure) and short-day exposed animals (Sinha Hikim et al. [1989b] (Endocrinology, 125:1829-1843) suggested that hypophysectomy, in general, resulted in similar, but slightly more severe regressive changes in the testis and germ cell population than those seen during seasonal regression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1456455 TI - Presence of pulmonary intravascular macrophages in the equine lung: some structuro-functional properties. AB - The pulmonary intravascular macrophages (PIMs) have been described in several species of animals. This study demonstrates for the first time that the equine lung has PIMs as resident phagocytes in its microvasculature. Their salient features such as globular surface coat, structures of the endocytic pathway, and related cell organelles closely resemble those of the calf, goat, and sheep. The exquisite organization of the coat globules in the form of a linear chain was structurally similar to the lipolytic lipase and the heparin-sensitive globular coat from PIMs of calf, goat, and sheep. Monastral blue (MB) when employed as a tracer to assess the phagocytic properties of equine PIMs induced similar modification of the globules of the coat into lipid droplets, reminiscent of neutral lipids. Lipids droplets (modified coat globules) were delivered into acid phosphatase-positive endosomes and lysosomes. Concurrently, the unaltered globules of the coat, probably internalized via fluid-phase constitutive pinocytoses, followed a different endocytic pathway. Large-scale platelet uptake by the PIMs was observed with thrombocytopenia in MB-treated ponies. The possible significance of hypothetical LDL-coat and the endocytic organelles as equivalents of synthetic apparatus of vasoactive lipids in the PIMs of horse needs to be assessed in future studies. PMID- 1456456 TI - Effects of sex steroids on the development of sexual dimorphism in mouse innominate bone. AB - The sexual dimorphism of the innominate bone was examined in 14 strains of mice. In female mice of all strains, the pubis was significantly longer and thinner than that in the strain-matched males. In 13 of 14 strains, the ischium in the male was longer and thicker than in the female. In the testicular-feminized male (Tfm) mouse, the ischium was longer and thinner than that in the wild-type male, resembling that of the wild-type female. The pubis of the Tfm mouse was longer than in the wild-type males. The pubis width in the Tfm mouse was between those of the wild-type male and female. Gonadectomy at ages of 5, 10, 20, 30, and 60 days in both sexes showed that the ischium develops as the female type when sex hormones are absent. In contrast, postnatal testicular androgen induces the male type ischium. Gonadectomy at 60 days had a slight effect on the pubis, indicating that sexual dimorphism of the pubis was determined before 60 days of age. Estrogen receptors (ER) were immunohistochemically demonstrated in bone cells of 0- to 60-day-old mice. ER was found exclusively in the periosteum of the pubis at the day of birth; however, it appeared in bone cells of all parts of pelvis at 10 60 days. These results indicate that sexual dimorphism of the pubis is consistent for the 14 mouse strains examined, and that the shape of the pubis is determined by sex steroids before 60 days of age. Since ER exist in the bone cells, morphogenesis of the pelvis may be regulated by these sex steroids. PMID- 1456457 TI - Immunohistochemical demonstration of melatonin in the female mink harderian gland. AB - In the Harderian gland of the female mink, either intact or killed after a bilateral ablation of the cervical superior ganglion, almost all of the cells of the alveoli were immunolabeled with anti-melatonin antiserum. Animals were killed during the day or during the night. The immunolabelling was observed only in the cytoplasm, while the nucleus remained unstained. Using successive dilutions of the antiserum on serial sections of the Harderian gland to qualitate the melatonin content, a circadian rhythm of melatonin immunoreactivity was observed. The intensity of immunofluorescence labelling was higher in intact animals killed during the day than in those killed during the night. These results could be explained by the inhibitory or stimulatory influence of pineal melatonin released during the night on melatonin synthesis or release in the Harderian gland, respectively. In the Harderian gland of ganglionectomized animals, the intensity of melatonin immunofluorescence was lower than in intact animals killed during the day. It is concluded that the Harderian gland might be involved in the perception of the day/night cycle and that melatonin synthesis/secretion was likely controlled by the cervical superior ganglion in this organ. PMID- 1456458 TI - Development of the liver in the chicken embryo. I. Hepatic cords and sinusoids. AB - Hemopoiesis in the liver of the chicken embryo begins on day 7 of incubation (Hamburger and Hamilton Stage 30) and peaks on day 14 (Stage 40). During this time frame, the differentiation of hepatic cells was examined by light microscopy, transmission and scanning electron microscopy, and morphometry. The avian liver is a closely packed mass of dendriform cords and discontinuous sinusoids. Hepatocytes are pyramidal in shape, and they ring the bile canaliculi which run through the centers of the cords. Semithin sections, made possible by infiltration and embedding in glycol methacrylate, were stained with hematoxylin and eosin to assess the general architecture of the organ and the lipid content of the hepatocytes and by the periodic acid-Schiff reaction and hematoxylin to visualize the cytoplasmic stores of glycogen. The number of hepatocytes with demonstrable glycogen fluctuates erratically in early hemopoiesis, and the proportion of glycogen-containing cells progressively increases as hemopoiesis climbs to a peak. Most differentiating hepatocytes are devoid of lipid droplets until Stages 39 and 40. From Stage 30 to 35, hepatocyte volume falls to its lowest value. Subsequently (Stages 36 to 40), cell volume increases and hepatocytes achieve a relatively uniform size. Ultrastructural changes in the differentiating hepatocytes, including alterations to the mitochondria, endoplasmic reticulum, and Golgi apparatus, are documented. These morphological and morphometric findings on the prehepatocyte population and hepatic vasculature cover 2 of the 3 elements deemed critical to hepatic hemopoiesis in many vertebrates. PMID- 1456459 TI - Growth of the normal human lower urinary tract from 12 to 21 weeks gestation. AB - Normal development of the human lower urinary tract was studied between the 14th and 20th week of gestation using 3 modes of fixation. Fixation by direct distension provides a high degree of reproducibility of parameters used to study the growth of the fetal bladder. Using this method, fetuses ranging from 12 to 21 weeks gestation were studied. Results obtained demonstrate that the length of the bladder, the inter-ureteric distance, and the distance between the apex of the trigone and the distal tip of the urethra occur in a linear mode. Furthermore, the rate of growth of the male urethra was evidently higher when compared to that of the female from the 12th week of gestation. Data from this work can be used for a more accurate assessment of cases with abnormal lower urinary tract development. PMID- 1456460 TI - Organization of the optic chiasm in the hatched chick. AB - In the hatched chick the fibers of the two optic nerves segregate into clearly defined bundles when they cross to the other side. These bundles run in horizontally oriented tiers. The tiers are demarcated by blood vessels and pial tissue. The organization of these tiers was investigated qualitatively and quantitatively using light and electron microscopy as well as tracer techniques. The fibers within the tiers cross to the contralateral optic tract without leaving their respective tier. The mean total number of tiers is 34 with a great individual variation. A preference in the superposition of one side over the other could not be observed. Comparing these data with our earlier study (Rager et al.: Anat. Embryol., 179:135-148, 1988) it can be concluded that neither the segregation of fibers into discrete bundles nor the variability in the number of alternating tiers seem to disturb the topography of fibers as it is achieved in the optic nerve. The pattern of vascularization correlates with the order of crossing axon bundles and contributes to the demarcation of the tiers. The chiasm is vascularized by the Aa. preopticae and the A. infundibularis. PMID- 1456461 TI - Accuracy and precision of computerized models of the anterior cranial base in young mice. AB - The quantitative analysis of craniofacial growth in experimental animals relies on computerized reconstructions in order to measure changes in form. The purpose of this study was to determine the validity of computerized three-dimensional models of the anterior cranial base in mice. Ten 1-day-old non-littermates were collected and the anterior cranial base was dissected free from surrounding connective tissues. Eleven measurements were recorded from these cartilages. Twenty developmentally equivalent mice were collected and fixed with either glutaraldehyde or formalin and the anterior cranial base from each specimen was subjected to computerized reconstruction. The corresponding 11 measurements were recorded from these models. Results showed that the measurements recorded from the computerized models were not significantly different from those recorded directly from the actual anterior cranial bases. Therefore, the reconstructions were considered accurate. An analysis of the coefficients of error revealed that measurements derived from the computerized models were significantly more precise than those recorded directly from the actual tissue. The computerized three dimensional reconstruction method provides accurate and precise models of the anterior cranial base in young mice. PMID- 1456462 TI - [The use of cryopreserved swine blood for in vitro feeding of the soft tick Ornithodoros moubata]. AB - Porcine stored blood has been used in the in vitro feeding of the soft tick Ornithodoros moubata through a Parafilm membrane. The efficiency of the feeding decreased after storage of 5 weeks by -20 degrees C. Through addition of 10(-3) M ATP/l the feeding results with frozen blood for duration of storage up to 200 days well agreed with the results of feeding tests with fresh porcine blood: The nymphs (N)1-3 fed the 4-5fold, the N4-6 the 2.7fold and the adults (A) the 1.9fold of their body weight. The feeding rate was 98.6% (N1-3); 92.7% (N4-5) and 81.9% (A). The mortality rate was under 10%. Females laid 130 eggs after blood meal. PMID- 1456463 TI - [The occurrence of Echinococcus granulosis and E. multilocularis in Thuringia]. AB - The occurrence of E. granulosus and E. multilocularis in the region of Thuringia is reported. Parasitological investigations showed 1421 E. granulosus metacestodes, 91.7% of them in lungs and 1.3% in livers of cattle, 6% in lungs and 1% in livers of pigs; that means an infestation rate at slaughter of 0.1% 0.3% in cattle and 0.001-0.004% or less in pigs resp. 90.1% of the hydatid cysts proved to be fertile even in a size of 1.5 cm diameter. Adult E. granulosus was found post mortem in 2 of 324 dogs. In the period from 1985 to 1988, only 11 dogs were infested with E. granulosus as found at autopsy all over the GDR. Out of 23,325 faecal samples 270 samples (1.2%) were positive for eggs of Taenia spp. The animals with egg-shedding were treated as infected with Echinococcus. In experimental infections of 12 Beagles the prepatent period ranged from the minimum of 34 days up to the maximum of 40 days. The detected E. granulosus strain could be identified as a dog-cattle strain. The microscopical examination of the intestine of 805 red foxes (Vulpes vulpes) revealed the presence of E. multilocularis in 12.7% of the animals. Thuringia is one of the endemic distribution area of E. multilocularis in Central Europe. In the west of Thuringia 25% of the foxes were found with E. multilocularis, in the remaining area (lowlands) only 3.3%. In some of mountainous areas, 40% of the foxes were infected with E. multilocularis. 2 cats of 58 from this region were infected with E. multilocularis. PMID- 1456465 TI - Human helminthosis in a rural community of Plateau State, Nigeria. AB - Urine and faecal samples were obtained from 1,517 people in Fier, a typical rural village in Plateau State, Nigeria, for a parasitological survey among the population. 643 (42.39%) persons were found to be infected with altogether 9 helminths, namely: Ascaris lumbricoides, hookworm, Taenia sp., Trichuris trichiura, Enterobius vermicularis, Schistosoma mansoni, S. haematobium, Hymenolepis nana and Strongyloides stercoralis. Age and religion as opposed to sex, type of sewage system, and type of housing had a significant effect (P < 0.05) on the prevalence rates of the helminths in the population. Snail vector survey for schistosomatosis revealed the presence of Bulinus (Bulinus) truncatus, Bulinus (Physopsis) globosus and Biomphalaria pfeifferi with the latter being the most common with brevifurcate cercariae, and xiphidiocercariae being the most common cercariae harboured by the snails. PMID- 1456464 TI - Behavioural aspects and their possible uses in the control of dracontiasis (guinea-worm) in Igwun river basin area of Imo State, Nigeria. AB - Individuals suffering from dracontiasis from Igwun river basin area of Imo State Nigeria were randomly chosen, examined and interviewed between December 1988 and March 1989 with a view to ascertain some of the behavioural aspects that could be of help in the control/eradication of this disease as well as to ascertain whether local medication was of any chemotherapeutic significance. Of 100 guinea worm patients males were significantly higher (P < 0.05) in number (63.0%). In the age-related distribution, children less than 10 years old and the members of the villages more than 60 years old accounted for only 5.0% of the patients whilst those in their productive years (10-60 year old) accounted for 95.0%. Only 10.5% of the respondents associated guinea-worm infection with the drinking of "polluted" water while most believed it was a familial trait (36.8%) or implicated their enemies (35.1%). As a result medications against the disease were mainly directed towards consulting the oracle and herbalists, and appeasing the gods. Most (98.0%) of them kept their dressing dry by refraining from immersing them in water. The concomitant behavioural aspects of these results are discussed in relation to their uses in the control/eradication of guinea-worm. PMID- 1456466 TI - Trials to infect Anopheles stephensi with Plasmodium yoelii nigeriensis by the membrane feeding technique. AB - The aim of this study was to find optimal conditions for the membrane feeding technique to obtain maximum infection rates of mosquitoes with Plasmodium yoelii nigeriensis. The results show that the malaria parasite Plasmodium yoelii nigeriensis is most infective to Anopheles stephensi mosquitoes on day 3 of the infection in the mice, 1 day before the peak of parasitaemia. The mortality rate of the mosquitoes fed on mice on day 3 after infection was the highest as compared to mosquitoes fed on other days after infection. Gametocytes from mice 3 days after infection were fed to mosquitoes by three different membrane feeding methods. The results indicate that feeding during the first 10 min after blood collection gave the highest infection rates. Keeping the blood meal at a pH of 7.2 yields higher infection rates than keeping it at pH of 8.5. Stirring of the blood and supplying it with CO2 is not necessary when feeding of the mosquitoes is completed within the first 10 min after collection of the blood. PMID- 1456467 TI - On the developmental velocity of Wucheria bancrofti larvae in vector mosquitoes of different susceptibility to filarial infections. AB - The developmental velocity of Wucheria bancrofti larvae was investigated in mosquito strains with different susceptibility to this filarial species. High susceptibility of the vector strains favoured fast filarial development, e.g. between 17.1 and 25.9% of all discovered larvae on day 13 p.i. had already migrated to the head and mouth parts of the more and partly even highly susceptible Anopheles gambiae, Culex pipiens quinquefasciatus and Aedes aegypti, respectively, whereas between 0 and 3.4% infective larvae had reached the head in the less susceptible Culex strains. On day 15 p.i. in all mosquito strains the majority of the larvae had reached infectivity. PMID- 1456468 TI - [Morphological and biological characterization of a pure strain of Eimeria mitis]. AB - A pure strain of Eimeria mitis was obtained from a crude field isolate by single oocyst inoculation of chicken. The strain was identified as Eimeria mitis by the morphology of the oocysts. Sporulated oocysts measured 16.1 +/- 2.1 microns in length and 13.6 +/- 1.0 microns in width. The shape index was 1.18. The prepatent period was 4 days and patency lasted 12 to 13 days. The highest number of oocysts was shed at day 6 after infection of chicken with 1 x 10(4), 5 x 10(4), or 1 x 10(5) oocysts and at day 8 after infection with 5 x 10(5) oocysts. A single infection of chicken with 1 x 10(4), 5 x 10(4), 1 x 10(5), or 5 x 10(5) oocysts resulted in reproduction values of 1:118,662, 1:15,720, 1:9,977 and 1:731, respectively. PMID- 1456469 TI - Observations on mansonellosis among the Ibos of Abia and Imo States, Nigeria. AB - Between November, 1988 and April, 1991, parasitological and symptomatological methods of diagnosis were used to survey the prevalence of mansonellosis among the Ibo population in Abia and Imo States of Nigeria. 1,197 or 28.6% of the 4,183 persons examined were positive for microfilariae of Mansonella perstans. The prevalence of mansonellosis was significantly higher (P < 0.05) among rural dwellers (34.6%) than among urban dwellers (22.5%), in males (30.8%) than in females (26.3%), in farmers (59.8%) and palm wine tappers (46.1%) than in civil servants (7.6%), and in persons 21 years of age and above (36.2%) than in those in the first two decades of life (9.4%). Clinical signs observed in most infected persons include body itching, joint and back pains, occasional giddiness and elephantoid scrotum. Body itching was the most commonly observed clinical sign (14.7%), followed by joint pains (12.41%) with elephantoid scrotum (3.5%) as the least. The public health implication of the findings is discussed. PMID- 1456470 TI - Annual performance reviews: are they worth it? PMID- 1456471 TI - Facial growth during adolescence in early, average and late maturers. PMID- 1456472 TI - An orthodontic study of temporomandibular joint disorders. Part 1: Epidemiological research in Japanese 6-18 year olds. AB - Malocclusion is considered one of the etiological factors of temporomandibular joint disorder (TMD). The purpose of this study was to investigate the prevalence of TMD and the relationship between TMD and the type of occlusion. The sample consisted of 7337 Japanese children, 6-18 years old, 3219 boys and 4118 girls. TMD symptoms were recorded as well as the type of occlusion in children with TMD. The prevalence of TMD overall was 12.2%. The prevalence increased with age and was slightly higher in girls (13%) than in boys 11.1%. This difference was not statistically significant. Joint sound as the only symptom was more common in younger subjects. TMD symptoms seemed more complicated with age when pain and abnormal jaw movement combined with sound. Joint sound was the most common symptom (89.3%), followed by the combination of sound and pain (2.2%). The incidence of other symptoms was under 1%. In subjects with TMD, 24.9% exhibited crowding, 20.1% had excessive overjet, 6.8% deep bite, 6.3% edge-to-edge bite, 5.6% anterior crossbite, 5.4% open bite, and 3.8% posterior crossbite. Morphologically normal occlusion was observed in 27.1%. In this study, many subjects with TMD had malocclusions. Early treatment may be important in the prevention of severe TMD. Although those with morphologically normal occlusions were included, a more detailed study concerning other causes of TMD is needed also. PMID- 1456473 TI - Blood flow changes in gingival tissues due to the displacement of teeth. AB - Changes in human gingival blood flow were measured using a Laser doppler flowmeter. The change of blood flow was correlated to the degree of force applied and there were variations in measurement of decreased blood flow among the subjects. The variation was attributed to the degree of tooth displacement and the size of the interdental space. This study examined the effect of tooth displacement on the gingival blood flow, as well as age and sex differences. Blood flow in gingival tissue was measured using a laser doppler flowmeter, and displacement of the maxillary incisors was measured using an eddy current sensor. The correlation coefficient of the decreased blood flow to the tooth displacement was 0.809, and it was higher than that to the degree of applied force (r = 0.625). The regression coefficient of decreased blood flow to the displacement of teeth was significantly correlated to the interdental space. The regression coefficient of decreased blood flow to the percentage of tooth displacement was independent of the interdental space. However, the regression coefficient of decreased blood flow to the percentage of tooth displacement was significantly higher in young subjects than in adults. PMID- 1456474 TI - The effects of artificial saliva and topical fluoride treatments on the degradation of the elastic properties of orthodontic chains. AB - The effect of artificial saliva and topical fluoride treatments on the force relaxation and change in force delivery by three brands of elastomeric chains over a 4 week period was studied. The effect of storage in air and in the different test media on the distraction to achieve forces of 150g and 300g was determined for the chains. The effect of the test media on load relaxation of the chains was also examined. Elastomeric chains exhibit good elastic behavior when distracted to an initial force of less than 300g. When forces exceeded 300g, permanent deformation occurred and the force delivery was less predictable. Exposure to artificial saliva and topical fluoride affected the elastic properties of the elastomeric chains and increased the distraction required to deliver both the 150g and 300g force. The increase in distraction for a force of 150g, however, was relatively small and probably insignificant in the clinical setting. The distraction required to produce 300g was significantly larger and appeared to be clinically significant. Pre-stretching the elastomeric chains by 100% of their initial length was not found to be advantageous in terms of the load relaxation behavior. There was less load relaxation found in chains that were immersed in distilled water and Acidulated Phosphate Fluoride than in chains exposed only to air. PMID- 1456475 TI - The influence of unilateral cleft lip and palate on maxillary dental arch morphology. AB - A sample of 97 untreated cleft lip and palate adult patients, with and without Simonart's band, was analyzed. The dimensions and form of the maxillary dental arches were analyzed. Comparison of this sample with a "normal" group indicated maxillary dental arch size and shape are distorted by the presence of a cleft which is characterized by a constriction that becomes more severe in the medial and anterior regions. The presence of Simonart's band affects the cleft arch form, redirecting the anterior extremity of the major segment towards the minor segment. PMID- 1456477 TI - TMJ biocompatible orthodontic treatment. AB - The papers summarized here indicate that TMJ dysfunction remains a complicated problem, requiring a multidisciplinary team approach. Psychological stress is an important factor in diagnosis. New concepts of joint function must be considered. The functional anatomy of the TMJ from an arthroscopic perspective should be studied. New treatment methods, such as the polycentric hinge joint articulator, should be considered. And finally, orthodontic diagnosis and treatment conventions need to be modified, from obtaining a complete history, clinical examination, arriving at a diagnosis and obtaining informed consent for treatment that may include psychological counseling, splint therapy, simultaneous fixed orthodontics and splint therapy and possible TMJ arthroscopic surgery for nearly all orthodontic patients. PMID- 1456476 TI - The asymmetric extraction decision. AB - Orthodontic study models, intraoral photographs, radiographs and diagnostic set up casts of four completed adult cases are presented to show the possibilities of atypical treatment planning to correct specific and unusual malocclusions. The cases presented required asymmetric dental extractions in order to achieve the desired treatment results. Three diagnostic procedures were used to assist in making the final treatment decisions; a Bolton tooth size analysis, a space available/space needed assessment, and a pretreatment diagnostic set-up. The completed treatment results closely approximate the original diagnostic predictions, and completely satisfied each patient's chief concern. Most orthodontic practices now treat increasing numbers of non-growing (adult) patients. Traditional extraction considerations must be modified to satisfy the treatment needs of this demanding patient population. PMID- 1456478 TI - Case report JB. Treatment of severe temporomandibular dysfunction with a combined orthodontic/surgical approach. PMID- 1456479 TI - Orthodontics with a tender touch. Part II. PMID- 1456480 TI - Systemic sclerosis. The role of the mast cell and cytokines. AB - This review of SSc has addressed the clinical features, pathophysiology involving the mast cell, T cell cytokines, and their interaction with other inflammatory cells (Figs 4 and 5). Therapeutic dilemmas and the future use of immunomodulatory therapy is also discussed. The allergist-immunologist may be the first physician to identify this insidious condition, since patients may present with cutaneous changes, swelling, pruritus, dyspnea, and with obstructive and restrictive findings on pulmonary function testing, or gastrointestinal symptoms, mimicking gastrointestinal hypersensitivity. PMID- 1456481 TI - Extremely elevated IgE. PMID- 1456482 TI - Treatment of atopic dermatitis with alpha 1-proteinase inhibitor. AB - Alpha 1-proteinase inhibitor (alpha 1-PI), a serine protease inhibitor, was tested for its efficacy for the treatment of recalcitrant atopic dermatitis. Atopic dermatitis affects both children and adults and has no established etiology. We hypothesized that during inflammation there is an excess of serine proteases and a deficiency of their naturally occurring inhibitors at the local site of tissue injury, even though there is a normal serum level of serine protease inhibitors. This pilot study consisted of a nonblinded trial using alpha 1-PI at a concentration of 20 mg/mL in an aqueous solution in an alternate day schedule in conjunction with a 1% cream of alpha 1-PI (Stage I) and a 5% cream of alpha 1-PI for maintenance therapy (Stage II). Before enrollment in this trial all six patients failed to respond to high potency topical steroids. Safety was gauged by careful clinical monitoring of subjective complaints, objective findings of erythema, edema, and serial measurements of blood chemistries and complete blood counts. Wound healing was documented by serial photography. Written informed consent was obtained from each patient. All six patients showed significant clinical improvement within 6 to 21 days of initiation of alternate day therapy. Alpha 1-PI stopped pain, pruritus, and promoted tissue healing without scarring in all six patients. No adverse side effects of therapy were documented by clinical history, physical examination, or by blood studies after 120 days of therapy. Atopic dermatitis may be one example where inflammation is due to an imbalance of serine proteases and their naturally occurring inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456483 TI - Aerobiology of the Colorado Rockies: pollen count comparisons between Vail and Denver, Colorado. AB - Pollen patterns were compared between Vail, CO (8,200 feet elevation), Aspen, CO (7,900 feet) and Denver, CO (5,280 feet) from 1984 through 1988. Counts were obtained at all sites with a volumetric intermittent cycling rotating impaction sampler. Aspen and Denver were compared in 1984, and Vail and Denver from 1985 through 1988. While counts were generally lower in the mountain sites than Denver, certain pollens, especially trees, were quite high. Ragweed was essentially absent from Aspen and Vail, and chenopod-amaranth counts were very low. Cedar, pine, and aspen frequently pollinated despite active snowfall. PMID- 1456484 TI - Measurement of IgG subclass antibodies to the group II antigen of Dermatophagoides pteronyssinus (Der p II) in sera from children with bronchial asthma. AB - Seven IgG-binding components in crude mite allergen extracted from Dermatophagoides pteronyssinus (Der p) were identified by immunoblotting analysis. Of these components, the 15-kDa protein was strongly recognized by IgG from patients with bronchial asthma, whereas it was less recognized by IgG from healthy individuals. Then, the 15-kDa protein was purified by reverse-phase high performance liquid chromatography and the protein was demonstrated to induce immediate positive skin reactions in patients with bronchial asthma. The N terminal amino acid sequence of the 15-kDa protein was also determined and was in agreement with that of Der p II. In an attempt to understand the role of IgG subclass antibody of patients with bronchial asthma, we quantitated the antibodies of IgG subclass to Der p II. The levels of antibodies of total IgG and of all IgG subclasses in patients with bronchial asthma who had never received immunotherapy were higher than those of nonatopic healthy individuals. The levels of Der p II-specific IgG1 and IgG4 in asthmatic patients were 1.97 times and 2.20 times higher, respectively, than those in the control group. The present study demonstrates that patients with bronchial asthma are able to produce antibodies of all IgG subclasses specific to Der p II in response to natural exposure to mite antigen. PMID- 1456485 TI - Clinical evaluation of the "Siriraj Spacer" in asthmatic Thai children. AB - We designed a new, washable, and collapsible bag spacer (the Siriraj Spacer) for use with metered-dose inhalers (MDI) by Thai asthmatic patients. The Siriraj Spacer consists of a mouthpiece, a front panel to which any type of MDI could be attached and a collapsible 800 mL ringed-plastic bag. Fifteen asthmatic children (6-13 years of age) were enrolled into a randomized, double-blind, triple crossover study (spanning a period of three days) to compare the clinical effectiveness of the Siriraj Spacer with that of the Volumatic Spacer (Glaxo, Inc., Research Triangle Park, NC, U.S.A.) and with the use of MDI alone. Medication used with the active method of administration was 2 puffs of albuterol (100 micrograms/puff) while 2 puffs from placebo MDI were used with the other two methods in succession. All children were stable asthmatic patients, and had been instructed how to use MDI properly by an open mouth technique just before the initiation of the study. Spirometry (FEV1, FVC, PEFR, and FEF25-75%) was followed for six hours after the administration of albuterol. The baseline FEV1s of the three study days were within 50% to 70% of the predicted values (with baseline variability of less than 20%). Data were expressed as percentage of improvement from baseline. By an analysis of variance with repeated measures, no significant differences were observed between pulmonary function data obtained with any of the three methods of bronchodilator administration (P > .05) at any time point throughout the 6-hour period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456486 TI - Buckwheat-induced anaphylaxis: a case report. AB - Buckwheat (Fagopyrum schulentum) is not taxonomically related to wheat and other cereal grains. Buckwheat flour is used as a wheat substitute in breads, biscuits, pancakes, and crepes. Occupational exposure to buckwheat flour has been associated with rhinitis, conjunctivitis, contact urticaria, and occupational asthma. We present a patient who developed urticaria and hypotension after ingestion of buckwheat crepes. Skin testing by the prick technique revealed 3+ positive reaction to buckwheat with negative reactions to other foods including wheat, egg white, and milk. RAST for anti-buckwheat IgE was strongly positive. Buckwheat ingestion is a potential cause of food-related anaphylaxis. There does not appear to be cross-reactivity between buckwheat and wheat allergy. PMID- 1456487 TI - Evaluation of immune complexes after immunotherapy with wheat flour in bakers' asthma. AB - Inhalant food allergy has been described many times in literature, but double blind clinical trials to support successful hyposensitization to these allergens has seldom been reported. Some authors have suspected that certain adverse reactions after immunotherapy may be mediated by immune complexes. Furthermore, the FDA does not recommend injection therapy with food extracts. We present a study on the detection of adverse effects after immunotherapy with an inhalant food (wheat flour) in a double-blind clinical trial in 26 patients with bakers' asthma. We investigated the presence of circulating immune complexes (CICs) after 2 years of treatment with hyposensitization to wheat flour. PMID- 1456488 TI - Increased incidence of stings in venom-sensitive patients. AB - We compared the histories of 29 venom-sensitive and 28 control subjects who were selected from our venom referral and general allergy clinics respectively. The variables in the study included insect avoidance knowledge, the number of stings during the previous 2 years, insects involved, and time spent out of doors per week. There was no significant difference between the two groups with respect to age. All venom-sensitive patients were well versed in avoidance techniques while only 3 of 28 controls (11%) claimed such knowledge. Venom-sensitive subjects were stung almost ten times more frequently than control subjects. Wasp stings were the most common, followed by yellow jacket, honey bee, and hornet. The venom sensitive patients also reported spending a greater amount of time outdoors (x 17.4 hours versus x 11.8, P < .05). An analysis of covariance showed that this difference in outdoor exposure was insufficient to account for the disparity in the number of stings. We conclude that other factors such as intrinsic attractants must be responsible for this phenomenon. PMID- 1456489 TI - Allergic bronchopulmonary aspergillosis and allergic aspergillus sinusitis: case report. PMID- 1456490 TI - Benzyl benzoate: acaricide or anti-asthmatic drug? PMID- 1456491 TI - Wheat-dependent exercise-induced anaphylaxis. PMID- 1456492 TI - [Human pancreatic lipase activity: review of methods and general recommendations]. AB - The properties of human pancreatic lipase are described, especially as regards the influence of the kind and the presentation of the substrate, as well as the effects of bile pigments and colipase. The authors have made a classification of the described methods for the determination of lipase activity in serum or plasma and have proposed recommendations for this assay. PMID- 1456493 TI - [Serum myoglobin: evaluation of two immunolatex methods. Comparison with a radioimmunoassay method]. AB - Latex immunoturbidimetric (ITA) and immunonephelemetric (INA) assays, were evaluated and compared to a radioimmunological assay (RIA) for the determination of serum myoglobin. Within-run and between-run assays and accuracy and linearity studies gave satisfactory results, very similar to those of RIA. Results were closely correlated with those of RIA for 100 samples of up to 2,000 micrograms/l (correlation coefficients respectively 0.96 and 0.97 for ITA and INA). Reference values (150 men and 150 women; range 20-65 years) were determined and expressed in percentiles. It is concluded that the two latex immunologic assays facilitate laboratory myoglobin evaluation (no radioactive material, short performance time). ITA is more suitable for emergency analysis and INA is more convenient for serial analysis and particular samples (presence of hemoglobin or chylomicrons). PMID- 1456494 TI - [Comparative study of LpAI lipoparticles, HDL cholesterol and apolipoprotein AI in a control population, in a group of subjects with coronary diseases, and in a group of subjects with angiographically normal coronary vessels]. AB - A new method for directly measuring LpAI lipoparticles containing apolipoprotein AI, but not apolipoprotein AII, is now disponible for laboratories. Concentrations of LpAI were measured in serum from 158 presumably healthy normolipidemic subjects (72 male, 86 female), for the age group 30-60 years. Concentrations of LpAI were also measured in subjects with angiographically defined coronary artery disease (coro+) and without angiographically defined coronary artery disease (coro-). After comparison of the groups, lipoprotein particle LpAI did not appear to be a better discriminative marker than HDL cholesterol or apolipoprotein AI for atherogen risk. PMID- 1456495 TI - Spectrophotometric determination of lipase activity in the presence of increased triolein concentration. AB - A novel approach for the determination of pancreatic lipase (EC 3.1.1.3) activity by a spectrophotometric method is described. Enzyme activity is measured in the presence of 1 mmol/l triolein, a concentration much higher than usually employed in turbidimetry. The primary reaction medium is optimized as regards bile salt and colipase concentrations. The released fatty acids are enzymatically determined via a secondary reaction scheme using the constituents of a commercially available kit. The proposed method is easy to perform and may prove useful in determining lipase activity of standard lipase preparations, which is required for indirect assays. In addition to satisfactory precision and linearity as well as close correlation with other lipase assays, the procedure described in the present paper by-passes a number of short-comings (eg uncontrolled increase in absorbance) inherent to the turbidimetric methods. PMID- 1456496 TI - Signal enhancement in fluorescence microscopy and flow cytometry using fluorescent liposome-antibody conjugates as second layer reagents. AB - We have developed small unilamellar liposomes (SUV) containing carboxyfluorescein for indirect immunophenotyping of cells by fluorescent microscopy and flow cytometry. Covalently coupled to anti-mouse Ig and anti-human Ig with mouse monoclonal antibodies and human typing antisera respectively, these conjugates can increase sensitivity by a factor of 10 compared to fluorescein isothiocyanate (FITC) conjugates. No increase in background fluorescence was observed. The reagents have been used to detect a low density antigen, the interleukin-2 receptor, on resting T-cells and to overcome the quenching effect of haemoglobin in fluorescent phenotyping of red cells. This has allowed to accurately estimate blood grouping in mixed fields and with small numbers of cells. We have determined the blood group of fetal red cells obtained from a chorionic villous sample at 10 weeks gestation and predicted severe hemolytic disease. This was confirmed by fetal sampling at 19 weeks and several intra-uterine transfusions were undertaken before a successful delivery at 36 weeks. Applications of the method in leucocyte phenotyping and transfusion medicine are discussed. PMID- 1456497 TI - Biosensors: a new realism. AB - For many years biosensors have been hailed as the solution to many analytical problems. There is general agreement that biosensors offer the potential for easy to-use, low-cost, rapid analysis. With such versatile, economic, reliable and cheap analytical devices at their disposal, manufacturers in industries as diverse as pharmaceuticals, food and drink, medical diagnostics and defence must surely be reaping vast profits from their biosensor-based products? In fact, biosensors have made only a very modest impact and this article attempts to present a realistic review of their current commercial potential. Consideration is given to the features and benefits of biosensors, the potential application markets, the impact of legislation, the needs of the user and the real commercial potential in the light of these factors and the existing competition. PMID- 1456498 TI - Modification of the selected method for the determination of serum iron. Substitution of bathophenanthroline by ferene S. AB - The previously selected method (1977) for the measurement of iron in human serum has been modified by the working group on Iron and Iron-Transport Proteins (Societe Francaise de Biologie Clinique). Ferene S is used as the chromogen, it is more sensitive and cheaper than bathophenanthroline. The sample size has been reduced from 2 to 0.5 ml. No interference could be shown with high concentrations of bilirubin, copper or hemoglobin. PMID- 1456499 TI - [Modified LDL and atherosclerosis. Nature of modifications. Physicochemical and biological properties]. AB - The role of plasma LDL in atherogenesis is now well established. Cholesteryl ester accumulation within macrophages leads to foam cell formation, an early atherosclerotic process. In vitro, foam cell formation scarcely ever occurs in the presence of native LDL. Modification of these lipoproteins is necessary for their binding to macrophage scavenger receptors. In vitro modifications reported have involved chemical reactions, physical mechanisms, enzymatic reactions, cellular interactions and association with macromolecules. In vivo, they can occur by glycation or desialylation, smoking or by hemodynamic interactions. Alterations of the physicochemical properties of LDL are induced by oxidation and include an increase in their density and their net electronegative charge, changes in lecithin composition, polyunsaturated fatty acid peroxidation of lipids and apolipoprotein B100 degradation. Apolipoprotein B100 fragmentation leads to an impairment of uptake through LDL receptors, while uptake through macrophage scavenger receptors is enhanced. Modified LDL have also other particularities such as cytotoxicity, chemotactism for circulating monocytes, inhibition of resident macrophage mobility, vasoconstriction, perturbation of the arachidonic acid cascade, involvement in haemostasis and immune mechanisms. Hypotheses concerning the role of modified LDL, in particular oxidized LDL, in atherogenesis open new therapeutic prospects. PMID- 1456500 TI - [LH and TSH receptors. A new family of G protein-coupled receptors]. AB - Monoclonal antibodies have been raised against porcine LH receptor and allowed to clone the corresponding messenger RNA from testicular cells. Cross hybridisation with the LH receptor clone allowed to isolate a clone corresponding to the human TSH receptor from thyroids. The structure of both receptors have been determined. They show similarities but also differences to other G protein coupled receptors. In particular a large extracellular domain is specific of that new family of receptors. Variant forms of the LH receptor lacking transmembrane domains have been isolated. The obtention of monoclonal antibodies against both receptors allowed immunochemical and immunocytochemical studies to be performed. The human LH receptor gene have been localized to chromosome 2p21 and TSH receptor gene to chromosome 14q31. The complete organisation of the human TSH receptor gene has been determined. PMID- 1456501 TI - Application of ECCLS guidelines to the analysis of Toxoplasma IgG and Rubella IgG using laboratory kits based on the Meia method. AB - The Meia method is an enzymo-immunoassay involving fluorometric detection, which is used in the Abbott IMx automatic analyzer. The purpose of this report was to analyse the Meia Toxoplasma gondii IgG antibody and Rubella IgG antibody assays, following ECCLS guidelines for the analysis of laboratory kits. The results showed that between-run imprecision for Rubella IgG was close to 15%; for Toxoplasma IgG the percentage was 13%. The mean recovery for Rubella IgG was 104% and 94% for Toxoplasma IgG. The carry-over for Rubella IgG was 0.64% and 0.26% for Toxoplasma IgG which, in both cases, was less than the analytical variability. Both Meia and Elisa showed a linear relationship in the analytical range of the method. Comparing Meia with the Elisa method, constant and proportional differences were found for IgG Rubella and proportional differences for IgG Toxoplasma. The Meia method has many positive analytical features to recommend and it can easily be used in a multidisciplinary laboratory, needing only a small number of serum samples. PMID- 1456502 TI - [An automatic gas scanning device, technical improvement for obtaining a favourable atmosphere for in vitro culture of anaerobic bacteria]. AB - All methods for growth of anaerobic bacteria on solid media depend on the elimination of atmospheric O2 through use of a palladium catalyst (Deoxo Catalyst), active in presence of at least 5% H2 with resultant formation of water. Anaerobic chambers and jars are the two conventional methods employed. Both are based on the elimination of air by means of a pump and its replacement with gas from a cylinder (evacuation-replacement technique). An alternative chemical technique for use in anaerobic jars consists of adding internal gas generating sachets. The former techniques are more efficient but the trend, particularly in the clinical laboratories, is to use the simpler chemical system that has two inconveniences: a slow establishment of anaerobiosis, and a high cost. We propose a new system that does not require a vacuum pump and consists in flushing anaerobic jars with a convenient gas mixture (H2, CO2, N2: 4.5; 5; 90.5 v/v) by means of an automaton regulating both time and gas flow. Gas-liquid chromatography analysis of the gas inside the jar shows a rapid elimination of gaseous O2, whose residual concentration is low enough to permit growth of all anaerobes of clinical interest, including those which are more O2-sensitive. Comparative qualitative and quantitative data obtained with all available techniques demonstrate the advantages of the new system. PMID- 1456503 TI - [Pertinence of simultaneous measurements of pO2 and sO2 on ABL 510]. AB - Blood tonometry is the only method to assess the accuracy of the pO2 determination on blood gas analyzers. ABL instruments by Radiometer were tested by two types of tonometry (film and bubble tonometry) and the validity of the algorithm for pO2 correction was analysed with these results. The role of the presentation of the specimen is also discussed. For the precision study on the ABL 510 analyzer, coefficients of variation for pO2 were < 0.37% and < 1.7% for within-run and day-to-day series respectively. pO2 accuracy was excellent. Linearity was verified between 0-620 mmHg (82.5 kPa), and interinstrument comparisons demonstrated a strict correlation with the Ciba-Corning 178 instrument. ABL 510 measures simultaneously oxygen saturation by spectrophotometry. Analytical results showed an acceptable level of imprecision, but the definition and the clinical significance of this parameter are ambiguous. PMID- 1456504 TI - [Hemodialysis and ferritinemia]. AB - Iron-deficiency is a common phenomenon in chronic renal diseases and haemodialysis patients, a treatment with iron or transfusions is always provided in an early preventive way; yet, an overload may appear. Serum ferritin, in spite of analytic variability, remains at the present time a good witness to appreciate patients' iron stores. Authors report the results obtained with four commercial reagents in healthy population and in haemodialysed children or adults. The comparison of results for this parameter shows that haemodialysed sera, with or without treatment, have the same behaviour with reagents as those of healthy subjects. PMID- 1456505 TI - [Quality assurance or quality control. Lessons from an intercomparison circuit]. AB - This article deals with the evaluation of the three year results of the French interlaboratory control for serum copper and zinc analysis. We pointed out some results interpreted on the basis of the existence of differences between the notions of quality control and total quality assurance. The main finding was a surprising change in the annual range in the final results of the laboratories. All 'good' laboratories in the first year showed a significant fall in their individual performance the second year. We can interpret that as a falling off of vigilance in relation with the self satisfaction after the publication of the first results. We concluded that good laboratory practices must be accompanied by a quality program not limited to an analytical control. PMID- 1456506 TI - [Use of nutritional supplements that increase the saturation degree of body fatty acids in bovines. An increase of atherogenic risk in man?]. PMID- 1456507 TI - Diagnostic applications of repetitive DNA sequences. PMID- 1456508 TI - Genes in the diagnosis of malignant disease. PMID- 1456509 TI - Epidermal growth factor-like activity in mares' milk. AB - Epidermal growth factor (EGF)-like activity was measured in mares' colostrum and milk by radioreceptor assay. Milk samples were collected from 22 mares 1 or more times during early lactation. Samples of colostrum were taken after parturition and before the foal first suckled (presuckle), within 6 hours after the foal first suckled (postsuckle), and on days 1, 2, 4, and 8 of lactation. In the 5 mares from which milk samples were obtained at each sampling time, presuckle colostral mean EGF-like activity (17.8 ng/ml) was greatest (P less than 0.05). The mean values for EGF-like activity at all other sampling times were not significantly different from each other (postsuckle colostrum, 9.7 ng/ml; day 1, 9.6 ng/ml; day 2, 8.5 ng/ml; day 4, 8.0 ng/ml; day 8, 7.8 ng/ml). PMID- 1456510 TI - Ultrasonography of the urinary tract of female sheep. AB - We determined the position, dimensions, and structure of the kidneys, ureters, bladder, and urethra of 62 female sheep by use of ultrasonography. A 5.0-MHz convex transducer was placed over the right flank to examine the kidneys, and a 5.0 MHz-linear transducer was used to examine the bladder and urethra transrectally. All examinations were performed on sheep in standing position. The left kidney was 7.1 to 8.9 cm long, 3.4 to 5.5 cm wide, and 3.3 to 4.7 cm deep. Diameter of the parenchyma and renal sinus of the left kidney ranged between 1.1 and 1.9 cm and 1.1 and 2.0 cm, respectively. Circumference of the medullary pyramids varied between 2.1 and 3.3 cm. Similar ultrasonographic measurements were obtained for the right kidney. The diameter of the bladder varied between 0.3 and 6.9 cm in 96.8% of the sheep. The diameter of the bladder could not be determined in 32% of the sheep because it was > 10 cm, and, therefore, was beyond the penetration depth of the scanner. The only part of the urethra that could be ultrasonographically visualized was the internal urethral orifice. It had diameter between 0.1 and 0.2 cm. The ureters could not be ultrasonographically visualized in any of the sheep examined. The urinary tract of 8 sheep was examined 10 times within 2 weeks to examine whether measurements were reproducible. The interassay variation coefficient determined ranged from 3.1 to 31.8%, although for most variables, it ranged between 5 and 11%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456511 TI - Radiographically determined growth dynamics of primary lung tumors induced in dogs by inhalation of plutonium. AB - Beagles were exposed to aerosols of 239PuO2, 238PuO2, or 239Pu(NO3)4. Exponential growth constants for 50 primary lung tumors (23 bronchioloalveolar carcinomas, 22 papillary adenocarcinomas, 5 adenosquamous carcinomas) were calculated in 37 dogs, using sequential thoracic radiography. A wide range in doubling time (6 to 287 days) was observed. Mean +/- SEM doubling time was 93 +/- 10 days for bronchioloalveolar carcinoma, 107 +/- 13 days for papillary adenocarcinoma, and 101 +/- 36 days for adenosquamous carcinoma. Lung tumor growth rate in dogs was comparable to that in human patients with similar histologic tumor types. Linear regression analysis revealed significant (P < or = 0.0001) correlation between doubling time and survival of individual dogs. Doubling time was not significantly dependent on tumor type, sex, age at time of diagnosis, initial lung deposition, or isotope. Extrapolating time to tumor onset from tumor doubling time cannot be used to reliably predict the onset of malignancy. PMID- 1456512 TI - Arterial blood gas tensions in healthy aged dogs. AB - Twenty-four healthy dogs > 8 years old were recruited. In each instance, arterial blood gas tensions were analyzed. The alveolar-to-arterial oxygen gradient (P[A a]O2) was calculated to assess adequacy of pulmonary gas exchange. Thoracic radiographs were evaluated to ensure lack of visible signs of pulmonary disease and that lung features were similar to those in aged dogs of previous reports. Unlike findings in aged human beings, arterial partial pressure of oxygen (PaO2) was not decreased in this group of aged dogs (mean +/- SD, 102.9 +/- 7.8 mm of Hg). Similarly, P(A-a)O2 also was not increased. The thoracic radiographic findings were consistent with those of previous reports of pulmonary changes in aged dogs. The extent of radiographic abnormalities and the PaO2 were not correlated. PMID- 1456513 TI - Effect of diet on results obtained by use of two commercial test kits for detection of occult blood in feces of dogs. AB - To evaluate the effect of diet on results obtained by use of 2 commercial test kits for detection of occult blood in feces, 5 dogs were fed 7 diets in randomized sequence. Dry and canned diets with various principal ingredients were evaluated. Each diet was offered twice over a 24-hour period, followed by a 36 hour nonfeeding period. Fecal specimens were collected twice daily, and tests for occult blood were performed within 12 hours. The dietary origin of fecal specimens was confirmed by use of colored markers fed with each diet, and was correlated with estimates of gastrointestinal tract transit time. A modified guaiac paper test and an o-tolidine tablet test were performed on each specimen. Of 59 specimens, 4 were positive for occult blood, using the o-tolidine tablet test. Three positive results were associated with a mutton-based canned diet, and 1 positive result was associated with a canned beef-based diet. Of 59 specimens, 11 were positive for occult blood, using the modified guaiac paper test. Four positive results were associated with the mutton diet, and 3 positive results were associated with the beef diet. Of the remaining 5 diets, 4 caused 1 positive reaction. Results were inconsistent with the null hypothesis that the distribution of positive occult blood test results is not affected by diet (P < 0.025), and indicate that diet can affect the specificity of peroxidase-based tests for detection of occult blood in canine feces. Diet modification prior to testing is recommended. PMID- 1456514 TI - Determination of protein concentrations and their molecular weight in tears from cats with normal corneas and cats with corneal sequestrum. AB - Protein concentration was determined, using the Bradford technique, in tears from cats with normal corneas and from cats with corneal sequestrum. Tears from the former group contained 5.81 +/- 2.29 mg of protein/ml; those from corneal sequestrum-affected cats contained 6.21 +/- 2.21 mg/ml. Difference between the 2 values was not significant. Molecular weight determination was made, using 4 to 20% sodium dodecyl sulfate-polyacrylamide gels. Molecular mass of proteins ranged from 263 to 14 kDa. There was no detectable difference in the band patterns for the 2 groups. PMID- 1456516 TI - Reference serum biochemical values for emus and ostriches. AB - Reference serum biochemical values were determined in blood samples from 15 male, 18 female, and 4 unsexed emus (Dromaius novaehollandiae) 1 to 48 months old. Serum biochemical values also were obtained for 19 male, 26 female, and 4 unsexed ostriches (Struthio camelus) 1 to 60 months old. Parametric (mean +/- 2 SD) and non-parametric (fifth to 95th percentile) reference ranges and linear trends as influenced by age were determined for enzyme activities and concentrations of glucose, inorganic phosphate, BUN, uric acid, creatinine, triglyceride, cholesterol, total protein, and albumin. Species differences for all analytes, except cholesterol and inorganic phosphate concentrations, were detected. Creatine kinase values in ostriches were higher than those in emus. There were no linear relationships between age and analyte values in emus, and sex did not significantly (P < 0.05) affect the values in emus. Analyte values in ostriches tended to increase with age, but cholesterol, creatine kinase, inorganic phosphate, and alkaline phosphatase concentrations decreased with age. Glucose, triglyceride, gamma-glutamyltransferase, and cholinesterase concentrations in ostriches were not linearly associated with age. Age had a greater effect on the analyte values of female ostriches than it did on male ostriches. Concentrations generally increased with age in female ostriches, except for cholesterol, cholinesterase, inorganic phosphate, and alkaline phosphatase concentrations, which decreased with age. PMID- 1456515 TI - Evaluation of an automated system for hemoglobin measurement in animals. AB - In veterinary medicine, PCV determined by centrifugation of blood in a microhematocrit tube is the most common clinical test used to initially assess and monitor anemic and polycythemic animals. In contrast, blood hemoglobin (Hb) concentration, rather than PCV, is generally determined in human patients. One automated system photometrically measures blood Hb concentration after conversion of Hb to azide methemoglobin without dilution and was found to be a simple and accurate instrument for use in human medicine. We evaluated the system for its accuracy in measuring blood Hb concentration in animals by comparing it with standard techniques and for its suitability in veterinary practice. Blood samples, anticoagulated with potassium EDTA, from 78 healthy animals (33 dogs, 17 cats, 13 horses, and 15 cows) and 58 dogs and 4 cats with various blood abnormalities (10 anemia, 11 polycythemia, 21 lipemia, 16 leukocytosis, and 6 icterus) were analyzed. In all species, blood Hb concentration of healthy animals determined by the system was comparable to that measured by standard cyanmethemoglobin methods (ie, an automated counter; rI = 0.987 to 0.998 and a hemoglobin kit, rI = 0.946 to 0.993). The aforementioned system also yielded similar values to those obtained by use of standard methods in anemic, polycythemic, and icteric dogs and cats. Moreover, the system reads the absorbance at 2 wavelengths to correct for turbidity, and therefore, accurately measured Hb concentration in blood samples with severe lipemia (triglycerides concentration > 500 mg/dl) and marked leukocytosis (> 50,000 WBC/microliter), whereas other standard Hb techniques are known to give falsely high results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456517 TI - Furosemide-induced electrolyte depletion associated with echinocytosis in horses. AB - Echinocytes have been incriminated in the pathogenesis of exertional diseases in horses. To evaluate the hypothesis that echinocytes are dehydrated erythrocytes, we decreased blood sodium and potassium concentrations in 4 horses by administering furosemide (1.0 mg/kg of body weight, q 12 h) for 2 days and we monitored CBC, serum and erythrocyte sodium and potassium concentrations, and echinocyte numbers. Serum sodium concentration decreased progressively over the 48 hours of furosemide administration, then returned to near baseline concentration at 168 hours. A statistically significant decrease (P < 0.05) in serum potassium concentration was observed at 24, 48, and 72 hours after initial furosemide administration, and remained less than the baseline value at the end of the study. Mean erythrocyte potassium concentration decreased rapidly and remained low at the end of the study. Minimal changes were observed in erythrocyte sodium concentration during the first 72 hours after furosemide administration, but the value was significantly (P < 0.05) increased at 168 hours. Type-I and type-II echinocyte numbers increased by 4 hours after furosemide administration and persisted throughout the study. Type-III echinocytes were not seen in baseline samples, but numbers increased only modestly after furosemide administration. Administration of epinephrine to well hydrated horses increased echinocyte numbers only minimally, indicating that splenic contraction was not the likely cause for the furosemide-associated increase. To determine whether the decrease in erythrocyte potassium concentration and increase in sodium concentration was caused by furosemide acting directly on the erythrocyte membrane, we quantified erythrocyte potassium and sodium concentrations before and after incubation with furosemide in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456518 TI - Reference hematologic values and morphologic features of blood cells in healthy adult llamas. AB - Hematologic values and cellular morphologic features were evaluated for 38 healthy adult llamas. Reference ranges were determined for PCV, reticulocyte concentration, leukocyte concentration, and leukocyte differential counts. The approach used in this study was to focus on hematologic values that may be determined by use of techniques readily available to the practicing veterinarian and nonveterinary laboratory. Unique cellular morphologic features commonly observed and interpreted as normal included large granular lymphocytes, hyposegmented eosinophil nuclei, folded erythrocytes, and hemoglobin crystals. PMID- 1456519 TI - Characterization of erythrocytic indices and serum iron values in healthy llamas. AB - An electronic particle counter with attached particle-size analyzer was configured to directly determine concentration, mean cell volume, and volume distribution of erythrocytes in llama blood. Blood from 38 healthy llamas was used to characterize erythrocytic measurements and serum iron values for this species. Volume distribution curves for llama erythrocytes were similar in shape to those of other species. These curves had a unimodal, symmetric shape with a tail skewed to the right. Reference ranges for directly measured mean cell volume, erythrocyte concentration, hemoglobin concentration, and mean cell hemoglobin concentration were 21 to 28 fl, 11.3 x to 17.5 x 10(6) cells/microliters, 12.8 to 17.6 g/dl, and 43.2 to 46.6 g/dl, respectively. Reference ranges for serum iron concentration, total iron-binding capacity, and transferrin saturation were determined to be 70 to 148 micrograms/dl, 230 to 370 micrograms/dl, and 22 to 50%, respectively. PMID- 1456520 TI - Variability of serum bile acid concentrations over time in dairy cattle, and effect of feed deprivation on the variability. AB - Twelve nonlactating dairy cows, free of signs of liver disease and with normal serum activities of liver-derived enzymes and normal liver biopsy tissue, were examined over a 72-hour period for serum total bile acid concentrations. The cattle were fed hay twice daily, and blood samples were obtained every hour for 24 hours, every other hour for 24 hours, then every hour for 24 hours. After 3 weeks, the study was repeated on 6 of the cattle, thus providing data for eighteen 72-hour periods. Serum bile acid concentration varied greatly over the 72 hours, with the range being from one third to 3 times the median. There were variations by as much as 60 mumol/L from 1 hour to the next. After another 3 weeks, 8 of the cattle were deprived of hay for 48 hours and then fed hay morning and afternoon of the third (last) day of the study. There was no significant reduction in bile acid concentration after withholding the hay, but the variability was reduced (P = 0.02) during the last 20 hours of the hay deprivation period. In 3 ancillary studies, serum bile acid concentrations were examined over a 48-hour period in 2 cows in early lactation, 3 cows in midlactation, and two 6-month-old heifers. The cows were fed hay and grain twice daily, and the heifers were fed only hay twice daily. In comparison with values for the 12 nonlactating cows fed hay twice daily, mean serum bile acid concentration in the recently freshened cows was significantly (P < 0.002) higher (62.9 vs 22.0 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456521 TI - Serum bile acid concentrations in clinically normal cattle: comparison by type, age, and stage of lactation. AB - Serum total bile acid concentrations were determined for various types and ages of cattle. There was extreme variability among all the cattle, but the variance was twice as large (0.50 vs 0.22 in logarithmic scale) for beef cattle than for dairy cattle. There was no significant difference in serum total bile acid concentrations between beef cattle and dairy cattle in midlactation. Values for calves < 6 weeks old and for 6-month-old heifers were significantly (P = < 0.05) lower than values for lactating dairy cows. The 5th to 95th percentile range of values (mumol/L) for beef cattle was 9 to 126; for lactating dairy cattle, 15 to 88; and for 6-month-old dairy heifers, 11 to 64. PMID- 1456522 TI - Evaluation of hemostatic analytes after use of hypertonic saline solution combined with colloids for resuscitation of dogs with hypovolemia. AB - The effects of hypertonic saline solution (HTSS) combined with colloids on hemostatic analytes were studied in 15 dogs. The analytes evaluated included platelet counts, one-stage prothrombin time, activated partial thromboplastin time, von Willebrand's factor antigen (vWf:Ag), and buccal mucosa bleeding times. The dogs were anesthetized, and jugular phlebotomy was used to induced hypovolemia (mean arterial blood pressure = 50 mm of Hg). Treatment dogs (n = 12) were resuscitated by infusion (6 ml/kg of body weight) of 1 of 3 solutions: HTSS combined with 6% dextran 70, 6% hetastarch, or 10% pentastarch. The control dogs (n = 3) were autotransfused. Hemostatic analytes were evaluated prior to induction of hypovolemia (baseline) and then after resuscitation (after 30 minutes of sustained hypovolemia) at 0.25, 0.5, 1, 6 and 24 hours. All treatment dogs responded rapidly and dramatically to resuscitation with hypertonic solutions. Clinically apparent hemostatic defects (epistaxis, petechiae, hematoma) were not observed in any dog. All coagulation variables evaluated, with the exception of vWf:Ag, remained within reference ranges over the 24-hour period. The vWf:Ag values were not statistically different than values from control dogs, and actual values were only slightly lower than reference ranges. Significant (P < or = 0.04) differences were detected for one-stage prothrombin time, but did not exceed reference ranges. The results of this study suggested that small volume HTSS/colloid solutions do not cause significant alterations in hemostatic analytes and should be considered for initial treatment of hypovolemic or hemorrhagic shock. PMID- 1456523 TI - Evaluation of serum fructosamine concentration as an index of blood glucose control in cats with diabetes mellitus. AB - Fructosamine, a glycated serum protein, was evaluated as an index of glycemic control in normal and diabetic cats. Fructosamine was determined manually by use of a modification of an automated method. The within-run precision was 2.4 to 3.2%, and the day-to-day precision was 2.7 to 3.1%. Fructosamine was found to be stable in serum samples stored for 1 week at 4 C and for 2 weeks at -20 C. The reference range for serum fructosamine concentration in 31 clinically normal colony cats was 2.19 to 3.47 mmol/L (mean, 2.83 +/- 0.32 mmol/L). In 27 samples from 16 cats with poorly controlled diabetes mellitus, the range for fructosamine concentration was 3.04 to 8.83 mmol/L (mean, 5.93 +/- 1.35 mmol/L). Fructosamine concentration was directly and highly correlated to blood glucose concentration. Fructosamine concentration also remained high in consort with increased blood glucose concentration in cats with poorly controlled diabetes mellitus over extended periods. It is concluded that measurement of serum fructosamine concentration can be a valuable adjunct to blood glucose monitoring to evaluate glycemic control in diabetic cats. The question of whether fructosamine can replace glucose for monitoring control of diabetes mellitus requires further study. PMID- 1456524 TI - Effects of ketamine infusion on halothane minimal alveolar concentration in horses. AB - Eight adult horses were used in a study to determine ketamine's ability to reduce halothane requirement. To obtain steady-state plasma concentrations of 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/ml, loading doses and constant infusions for ketamine were calculated for each horse on the basis of data from other studies in which the pharmacokinetic properties of ketamine were investigated. Blood samples for determination of plasma ketamine concentrations were collected periodically during each experiment. Plasma ketamine concentrations were determined by capillary gas chromatography/mass spectrometry under electron impact ionization conditions, using lidocaine as the internal standard. Halothane minimal alveolar concentration (MAC; concentration at which half the horses moved in response to an electrical stimulus) and plasma ketamine concentration were determined after steady-state concentrations of each ketamine infusion had been reached. Plasma ketamine concentrations > 1.0 microgram/ml decreased halothane MAC. The degree of MAC reduction was correlated directly with the square root of the plasma ketamine concentration, reaching a maximum of 37% reduction at a plasma ketamine concentration of 10.8 +/- 2.7 micrograms/ml. Heart rate, mean arterial blood pressure, and the rate of increase of right ventricular pressure did not change with increasing plasma ketamine concentration and halothane MAC reduction. Cardiac output increased significantly during ketamine infusions and halothane MAC reduction. Our findings suggest that plasma ketamine concentrations > 1.0 micron/ml reduce halothane MAC and produce beneficial hemodynamic effects. PMID- 1456525 TI - Pharmacokinetics of metronidazole and its concentration in body fluids and endometrial tissues of mares. AB - Serum concentrations of metronidazole were determined in 6 healthy adult mares after a single IV injection of metronidazole (15 mg/kg of body weight). The mean elimination rate (K) was 0.23 h-1, and the mean elimination half-life (t1/2) was 3.1 hours. The apparent volume of distribution at steady state was 0.69 L/kg, and the clearance was 168 ml/h/kg. Each mare was then given a loading dose (15 mg/kg) of metronidazole at time 0, followed by 4 maintenance doses (7.5 mg/kg, q 6 h) by nasogastric tube. Metronidazole concentrations were measured in serial samples of serum, synovia, peritoneal fluid, and urine. Metronidazole concentrations in CSF and endometrial tissues were measured after the fourth maintenance dose. The highest mean concentration in serum was 13.9 +/- 2.18 micrograms/ml at 40 minutes after the loading dose (time 0). The highest mean synovial and peritoneal fluid concentrations were 8.9 +/- 1.31 micrograms/ml and 12.8 +/- 3.21 micrograms/ml, respectively, 2 hours after the loading dose. The lowest mean trough concentration in urine was 32 micrograms/ml. Mean concentration of metronidazole in CSF was 4.3 +/- 2.51 micrograms/ml and the mean concentration in endometrial tissues was 0.9 +/- 0.48 micrograms/g at 3 hours after the fourth maintenance dose. Two mares hospitalized for treatment of bacterial pleuropneumonia were given metronidazole (15.0 mg/kg, PO, initially then 7.5 mg/kg, PO, q 6 h), while concurrently receiving gentamicin, potassium penicillin, and flunixin meglumine IV. Metronidazole pharmacokinetics and serum concentrations in the sick mares were similar to those obtained in the healthy mares. PMID- 1456526 TI - Effects of xylazine on airway function in ponies with recurrent airway obstruction. AB - The effect of IV administration of the alpha 2-adrenoceptor agonist xylazine hydrochloride (0.5 mg/kg of body weight) was examined in ponies with recurrent obstructive pulmonary disease, commonly called heaves. Six ponies with the disease (principals) were studied during clinical remission and during an acute attack of airway obstruction precipitated by stabling and feeding of dusty hay. Six control ponies were also studied. In principal ponies with airway obstruction, xylazine administration significantly (P < 0.05) decreased pulmonary resistance and increased dynamic compliance, but did not affect PaO2 or PaCO2. The alpha 2-antagonist yohimbine blocked the pulmonary effects of xylazine. Administration of saline solution was without effect in both groups of ponies at all periods and xylazine did not have effect in controls or in principals in clinical remission. PMID- 1456527 TI - Effect of the somatostatin analogue octreotide on gastric fluid pH in ponies. AB - The effect of the somatostatin analogue, octreotide, on gastric fluid pH was investigated in 4 ponies. Gastric fluid pH was determined after SC administration of octreotide or physiologic saline solution (control). A baseline sample of fluid was obtained, the agent was given, and 8 additional samples were collected hourly. Administration of octreotide at all dosages tested (0.1, 0.5, 1.0, and 5.0 micrograms/kg of body weight) increased gastric pH to > 5.0. Baseline values were consistently < 2.7. Administration of octreotide at these same dosages induced gastric pH values > 4.0 for 2.4 +/- 1.2, 4.8 +/- 0.8, 5.7 +/- 1.3, and 5.4 +/- 2.6 (mean +/- SD) continuous hours, respectively. Treatment at all dosages increased the pH of gastric fluid, compared with control values. The duration of the increase in pH was significantly (P < 0.05) different than that of the control treatment, even for the lowest dosage, 0.1 microgram/kg. PMID- 1456528 TI - Potential use of simple manganese salts as antioxidant drugs in horses. AB - The scavenging of superoxide radicals by endogenous and therapeutically administered superoxide dismutases may prevent superoxide-mediated oxidative stress leading to lipid peroxidation, membrane lysis, and cell death in a wide variety of normal and pathologic states. Simple inorganic manganous salts such as MnCl2 also have superoxide dismutase-like activity and are extremely inexpensive, compared with enzymatic superoxide dismutase preparations. In this study, we explored the use of Mn salts as antioxidant drugs. We used the percentage of inhibition of nitroblue tetrazolium reduction by superoxide as a measure of the amount of superoxide dismutase-like activity. We found concentration-related increases in superoxide scavenging activity in simple buffer solutions upon addition of 1.25, 2.5, and 5.0 microM MnSO4. To determine whether Mn salts can inhibit oxidative damage in tissues, we used an in vitro model of lipid peroxidation in ischemic and reoxygenated rat liver slices. Concentrations of 10, 100, and 1000 mumoles MnCl2/L of buffer significantly decreased indicators of lipid peroxidation believed to be initiated by intracellular superoxide. We then determined the effectiveness of MnCl2 as a superoxide scavenger in conscious horses by measuring the superoxide scavenging ability of equine plasma before and during intravenous infusions of 1.0 L volumes of 0.9% saline solution containing 0, 12.5, or 25 mM MnCl2. Plasma Mn concentrations, which were determined by atomic absorption spectrophotometry, increased as a function of time and dose. Intravenously administered MnCl2 concomitantly produced dose-related increases in superoxide scavenging ability of equine plasma at 15, 30, 45, and 60 minutes after the onset of infusion, compared with preinfusion control values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456529 TI - Comparative aspects and sex differentiation of plasma sulfamethazine elimination and metabolite formation in rats, rabbits, dwarf goats, and cattle. AB - Plasma disposition and urinary recovery of sulfamethazine (SMZ), its N4 acetylated metabolite (N4AcSMZ), and 2 of its hydroxylated metabolites--5 hydroxysulfamethazine (5OHSMZ) and 6-hydroxymethylsulfamethazine (6CH2OHSMZ)- were determined in either sex of 4 animal species: rats, dwarf goats, rabbits, and cattle. Rats, rabbits, and dwarf goats had significant (P < 0.01) sex difference in SMZ plasma clearance. Male rats had higher plasma clearance than did female rats, and excreted higher amounts of the hydroxy metabolites and lower amounts of N4AcSMZ. The N4AcSMZ metabolite was predominant in plasma and urine of rabbits. Male rabbits had higher plasma clearance than did female rabbits, but differences in metabolite profile were not apparent. With regard to plasma SMZ elimination, the situation in goats was opposite to that in rats. Male goats had considerably lower clearance than did female goats. This was associated with a lower hydroxylation rat in males. Plasma half-life of SMZ in cows was lower than that in bulls, probably because of a smaller distribution volume in cows. Compared with elimination via urine, elimination via milk was negligible in cows. Significant differences in metabolite profiles were not found between bulls and cows. Similar to those in rats and mice, hormone-dependent xenobiotic metabolic pathways may exist in other species. Depending on species and xenobiotic compound residue concentrations of xenobiotics, their metabolites, or both may differ with sex of the animal, or may be altered after treatment with anabolic hormones. PMID- 1456530 TI - Effects of intramuscular administration of glycosaminoglycan polysulfates on signs of incipient hip dysplasia in growing pups. AB - We tested the hypothesis that treatment of growing, susceptible (to hip dysplasia) pups by IM administration of glycosaminoglycan polysulfates would mitigate the signs of incipient hip dysplasia. In 1 experiment, 7 pups, selected at random from 2 litters, were administered glycosaminoglycan polysulfates (2.5 mg/kg of body weight, IM) twice weekly, and 7 control pups from the same litters were given sterile buffered 0.9% saline solution from the age of 6 weeks to 8 months. Hip joints were examined by radiography, with pups in the standard, limbs extended position. At 8 months of age, all pups in this experiment did not manifest femoral head subluxation radiographically. The Norberg angle, a measure of coxofemoral congruity, improved from a mean +/- SEM value of 102 degrees +/- 1 degrees in controls to 106 degrees +/- 1 degrees in treated pups (P = 0.008). Pups were not subjected to necropsy. In the second experiment, 8 pups were selected at random from 2 litters and were administered 5 mg of glycosaminoglycan polysulfates/kg, IM, twice weekly from 6 weeks to 8 months of age. Similarly, 8 control pups were administered saline solution. At 8 months of age, hip joints were examined by radiography with pups in the standard position; at necropsy, intra-articular tissues were evaluated macroscopically and biochemically. Of 8 treated pups, none had subluxation radiographically, whereas 4 of 8 control dogs had femoral head subluxation. Mean Norberg angle on the radiographs was 109.7 degrees +/- 1.6 degrees for the treated group and was 101.5 degrees +/- 1.6 degrees for controls, representing a mean improvement in coxofemoral congruity of 8.2 degrees in the treated pups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456531 TI - Effect of hypertonic and isotonic saline solutions on plasma constituents of conscious horses. AB - Blood constituents and vascular volume indices were determined in 5 standing horses by use of 2-period crossover experimental design. Horses were either administered hypertonic (2,400 mosm/kg of body weight, i.v.) or isotonic (300 mosm/kg, i.v.) saline solution. Each solution was administered at a dosage of 5 ml/kg (infusion rate, 80 ml/min). Samples for determination of PCV, plasma volume, blood volume, plasma osmolality, total amount of plasma protein and plasma concentrations of protein, Na, K, and Cl were collected at 0 hour (baseline, before fluid infusion) and 0.5 hour (at the end of fluid infusion), and subsequently, at 0.25- or 0.5-hour intervals for 4.5 hours. All horses were given the predetermined dose of fluids by 0.5 hour after beginning the saline infusion. Values of P < or = 0.05 were considered significant. Administration of hypertonic saline solution was associated with decreased mean body weight by 4.5 hours, but weight change after isotonic saline administration was not significant. Other than body weight and plasma protein concentration, between trial difference (treatment effect) was not observed for any measured variable or index. The F values indicated that increasing the number of horses would have not changed these results. A time effect was evident across both trials, so that mean (+/- SD) plasma volume increased (12.3 +/- 1.07%) and mean plasma protein concentration (-12.1 +/- 1.03%) and PCV (-11.9 + 0.67%) decreased proportionately and transiently in association with administration of either fluid at that volume. Other time effects included increased plasma osmolality and Na and Cl concentrations. Blood volume estimates and total amount of plasma protein remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456532 TI - Hemodynamic and respiratory responses to variable arterial partial pressure of oxygen in halothane-anesthetized horses during spontaneous and controlled ventilation. AB - Cardiovascular and respiratory responses to variable PaO2 were measured in 6 horses anesthetized only with halothane during spontaneous (SV) and controlled (CV) ventilation. The minimal alveolar concentration (MAC) for halothane in oxygen was determined in each spontaneously breathing horse prior to establishing PaO2 study conditions--mean +/- SEM, 0.95 +/- 0.03 vol%. The PaO2 conditions of > 250, 120, 80, and 50 mm of Hg were studied in each horse anesthetized at 1.2 MAC of halothane and positioned in left lateral recumbency. In response to a decrease in PaO2, total peripheral resistance and systolic and diastolic arterial blood pressure decreased (P < 0.05) during SV. Cardiac output tended to increase because heart rate increased (P < 0.05) during these same conditions. During CV, cardiovascular function was usually less than it was at comparable PaO2 during SV (P < 0.05). Heart rate, cardiac output, and left ventricular work increased (P < 0.05) in response to a decrease in PaO2, whereas total peripheral resistance decreased (P < 0.05). During SV, cardiac output and stroke volume increased and arterial blood pressure and total peripheral resistance decreased with duration of anesthesia at PaO2 > 250 mm of Hg. During SV, minute expired volume increased (P < 0.05) because respiratory frequency tended to increase as PaO2 decreased. Decrease in PaCO2 (P < 0.05) also accompanied these respiratory changes. Although oxygen utilization was nearly constant over all treatment periods, oxygen delivery decreased (P < 0.05) with decrease in PaO2, and was less (P < 0.05) during CV, compared with SV, for comparable PaO2 values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456533 TI - Arteriovenous differences for glutamine in the equine gastrointestinal tract. AB - Glutamine has been shown to be an important metabolic substrate of enterocytes in many animals, including cats, dogs, hamsters, human beings, monkeys, rabbits, rats, and sheep. To determine whether glutamine is important in the metabolism of cells of the equine gastrointestinal tract, we examined transintestinal differences in glutamine concentrations in the arterial and venous circulation, and measured activity of the major glutamine catabolizing enzyme, glutaminase. Arteriovenous differences provide an index of the amount of a given substrate removed by the tissue across which the measurements are made, and commonly are expressed as a percentage of substrate removed, or percent extraction. Arteriovenous differences for glutamine were determined in 7 anesthetized adult horses (weight, 450 to 500 kg) before and after an i.v. glutamine infusion. The mean baseline arterial glutamine concentration (+/- SEM) was 572 +/- 24 microM; this concentration quadrupled (to 2,167 +/- 135 microM, P less than 0.01) 1 minute after i.v. bolus infusion of a 17.5-g glutamine load. Baseline extraction by the portal-drained viscera was 7.5 +/- 1.5%; this value increased to 18 +/- 2% at 1 minute (P less than 0.01) and had returned to baseline values 60 minutes later. Arteriovenous differences were greatest across the jejunum (11.8 +/- 1.8% in the baseline period vs 33.1 +/- 3.1% at 1 minute, P less than 0.001), with smaller differences across the colon, suggesting that the jejunum was the more avid utilizer of glutamine. Glutaminase activity was 4.38 +/- 0.16 and 4.00 +/- 0.60 mumol/mg of protein/h under standard conditions in jejunal and ileal mucosa, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456534 TI - Regional brain blood flow during prolonged submaximal exercise in ponies. AB - Experiments were carried out on 8 healthy ponies to examine the effects of prolonged submaximal exercise on regional distribution of brain blood flow. Brain blood flow was ascertained by use of 15-microns-diameter radionuclide-labeled microspheres injected into the left ventricle. The reference blood was withdrawn from the thoracic aorta at a constant rate of 21.0 ml/min. Hemodynamic data were obtained with the ponies at rest (control), and at 5, 15, and 26 minutes of exercise performed at a speed setting of 13 mph on a treadmill with a fixed incline of 7%. Exercise lasted for 30 minutes and was carried out at an ambient temperature of 20 C. Heart rate, mean arterial pressure, and core temperature increased significantly with exercise. With the ponies at rest, a marked heterogeneity of perfusion was observed within the brain; the cerebral, as well as cerebellar gray matter, had greater blood flow than in the respective white matter, and a gradually decreasing gradient of blood flow existed from thalamus hypothalamus to medulla. This pattern of perfusion heterogeneity was preserved during exercise. Regional brain blood flow at 5 and 15 minutes of exercise remained similar to resting values. However, at 26 minutes of exercise, vasoconstriction resulted in a significant reduction in blood flow to all cerebral and brain-stem regions. In the cerebellum, the gray matter blood flow and vascular resistance remained near control values even at 26 minutes of exercise. Vasoconstriction in various regions of the cerebrum and brainstem at 26 minutes of exertion may have occurred in response to exercise-induced hypocapnia, arterial hypertension, and/or sympathetic neural activation. PMID- 1456535 TI - Temporal lectin histochemical characterization of porcine small intestine. AB - A variety of biotinylated lectins was applied to formalin-fixed intestinal sections from isolator-reared pigs ranging in age from newborn through 12 weeks. Lectin binding to brush borders of villus enterocytes, crypt enterocytes, and dome epithelium, and lectin reactivity within goblet cells and Brunner's glands was semiquantified by microscopy and was used to estimate temporal changes in complex carbohydrates of enteric epithelium. Although variability in binding scores often was observed among pigs of the same age, several general patterns of lectin binding were detected. Dolichos biflorus and Ulex europaeus lectins had increasing binding to brush border membranes as pigs aged. The Dolichos biflorus, however, had decreased binding at the 12-week time point. Neuraminidase-treated Arachis hypogaea and Triticum vulgaris were associated with high mean binding scores at all time points. Canavalia ensiformis bound, with high mean score at all time points, to villus but not to crypt enterocytes. Arachis hypogaea was associated with variable but often high binding scores, regardless of pig age. Succinylated wheat germ agglutinin bound more to crypt than to villus enterocytes. Goblet cells were generally less reactive than were corresponding villi and crypts. Dome epithelium reactivity varied with the lectin used, whereas Brunner's glands reacted with all lectins tested. We conclude that age and regional variations in lectin binding may reflect differences in intestinal function and differentiation. Because complex carbohydrates may act as cell surface receptors for a variety of enteric pathogens, our results indicate that these differences may be partially responsible for age and anatomic differences in susceptibility or resistance to enteric disease. PMID- 1456536 TI - Bacterial survival, lymph node changes, and immunologic responses of cattle vaccinated with standard and mutant strains of Brucella abortus. AB - Forty-eight cattle were used in 4 experiments; 6-week-old calves in experiments 1 3 (n = 24) and 10-month-old heifers in experiment 4 (n = 24). In experiments 1-3, 7 groups of 3 calves each were inoculated SC with 5 strains of Brucella abortus: virulent strain 2308 (2 groups), vaccine strain 19 (2 groups), and mutant strains RB51. 19 delta 31K, and 19 delta SOD. Sera and lymph node tissues were examined at 2-week intervals for evidence of infection. At postinoculation (PI) week 12, 2 calves in each group were given dexamethasone for 5 days. Calves were then euthanatized and lymphoid tissue, spleen, liver, and bone marrow were examined for evidence of B abortus. Calves given strain 2308 had large numbers of bacteria in their lymph nodes, marked granulomatous lymphadenitis in the deep cortex, and loss of lymphoid cells in superficial cortical areas. In addition, they had high serum antibody titers at PI week 16. Calves given strain 19, or genetic mutants derived from strain 19, cleared bacteria from lymph nodes more rapidly, had less lymphoid destruction, and developed antibody titers that did not persist for 16 weeks. The RB51 strain (rough) was cleared most rapidly from lymphoid tissues and induced serum antibody responses only to the core of the lipopolysaccharide molecule. Treatment of calves with dexamethasone did not cause B abortus to reappear in tissues of any calves, nor did serum antibody titers increase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456537 TI - Systemic and pulmonary antibody responses of calves to Pasteurella haemolytica after intrapulmonary inoculation. AB - Systemic and pulmonary antibody responses of calves to Pasteurella haemolytica were evaluated by measuring immunoglobulin production in blood for 9 days and in pulmonary lavage fluid for 7 days after intrapulmonary inoculation. Clinical signs, pulmonary lesions, pulmonary and systemic inflammatory response, and amount of antigen in lavage fluid were used to evaluate the response of calves to challenge with P haemolytica. The pulmonary response consisted of production of IgG, IgE, and IgM antibodies to P haemolytica antigens and a 17- to 68-fold increase of cells in lavage fluid 8 hours after inoculation, with a gradual decrease toward normal. Antibodies of the IgM isotype to P haemolytica were demonstrated as early as 8 hours through 7 days after inoculation in 3 of 3 calves. Of the anti-P haemolytica isotypes, IgM was found in the highest concentration. In all of the inoculated calves, IgE was found 1 to 2 days after inoculation, and IgG was found in 2 of 3 inoculated calves from day 1 through 7 after inoculation. Detection of IgG correlated with smaller pulmonary lesions. Immunoglobulin A was not detected in lavage fluid. Serum was evaluated for IgG and IgM antibody response to P haemolytica. Specific IgM was detectable 5 days after inoculation, and IgG was detectable 7 days after inoculation. Pasteurella haemolytica antigens were not detected in serum or plasma. A transient increase in neutrophil count was found 8 hours after inoculation, with return to baseline values by 24 hours after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456538 TI - Effect of calf age and Salmonella bacterin type on ability to produce immunoglobulins directed against Salmonella whole cells or lipopolysaccharide. AB - A commercially available Salmonella bacterin was administered to Holstein calves starting at 1 to 19 weeks of age. Serum samples were obtained before administering bacterin and at 2-week intervals thereafter. An ELISA with Salmonella dublin lipopolysaccharide (LPS) or S dublin whole cells as antigen, was used to measure specific IgG and IgM responses. Antibody responses to LPS were not detected from calves < 12 weeks old inoculated with killed bacterin. Immunoglobulin responses to whole-cell antigen were detected from all age groups of calves inoculated with the same killed Salmonella bacterin. Calves < 11 weeks old are able to produce immunoglobulins to some whole-cell antigens, but are unable to produce anti-LPS immunoglobulins when inoculated with killed Salmonella bacterin. This age-related response to killed Salmonella antigens may account, in part, for increased susceptibility to salmonellosis in calves < 12 weeks old. In comparison to the response for killed antigen, 8 calves given modified-live aromatic-dependent S dublin bacterin at 1 to 3 weeks of age had detectable anti LPS immunoglobulins after immunization, although the response was not as rapid and was of a lesser magnitude than that of older calves given killed Salmonella bacterin. PMID- 1456539 TI - Monophosphoryl lipid A-induced immune enhancement of Brucella abortus salt extractable protein and lipopolysaccharide vaccines in BALB/c mice. AB - A study was conducted to determine the effect of monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM) as adjuvants on the protective responses in BALB/c mice vaccinated with Brucella abortus salt-extractable protein (BCSP) or proteinase-K-treated B abortus lipopolysaccharide (PKLPS). Mice were vaccinated with different doses of BCSP or PKLPS given alone or in combination with MPL or TDM. Mice were challenge-exposed 4 weeks later with virulent B abortus strain 2308. Two weeks after challenge exposure, the number of B abortus colony-forming units (CFU) per spleen, spleen weights, and spleen cell interleukin 1 production were measured. Serum IgG and IgM concentrations specific for vaccinal immunogens were measured before and after challenge exposure with B abortus. Spleen weights and mean B abortus CFU per vaccine group were significantly lower in BCSP- and PKLPS-vaccinated mice, compared with those of nonvaccinated control mice. Monophosphoryl lipid A enhanced the suppression of splenic infection when given with the BCSP vaccine, but not when given with the PKLPS vaccine. Trehalose dimycolate had no effect on mean CFU when given with BCSP, but incorporation of TDM resulted in a significant increase in mean CFU when given with PKLPS. Spleen weights in BCSP- or PKLPS-vaccinated mice were not different when these vaccines were combined with MPL or TDM. Because of the wide variation in the results, we could not conclude that vaccination with BCSP or PKLPS alone, or in combination with MPL altered spleen cell interleukin-1 production in B abortus-infected mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456541 TI - Ultrastructural mucosal injury after experimental ischemia of the ascending colon in horses. AB - The ultrastructural injury that develops sequentially in the ascending colon during experimentally induced ischemia was examined in 6 halothane-anesthetized horses. Colonic ischemia was created by 2 types of vascular occlusion 24 cm proximal and distal to the pelvic flexure. In all horses, transmural vascular compression was created. The colonic venous circulation was obstructed in 3 horses, whereas in the other 3 horses, arterial and venous circulation was obstructed. Two additional horses were anesthetized as controls for determination of any morphologic alterations associated with the experimental protocol. Full thickness colonic biopsy specimens were obtained from the antimesenteric border of the pelvic flexure at 0, 0.25, 0.5, 1, 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5, 4, 4.5, and 5 hours during occlusion, and were studied by light and transmission electron microscopy. Morphologic alterations did not develop in the colon of control horses. Mucosal congestion was observed by light microscopy in the colon of horses with experimentally induced ischemia, but congestion developed early in those with obstructed colonic venous circulation, compared with those having arterial and venous obstruction. Inter- and intracellular vacuolation and loss of staining initially resulted in groups of 3 to 5 superficial luminal epithelial cells. Alterations in the glandular epithelium lagged behind those in the superficial epithelium, but were observed in both groups by 2 hours of obstruction. These changes progressed to 100% sloughing of all epithelium by 4.5 to 5 hours. The initial cellular alterations, which were observed by transmission electron microscopy, developed at 0.25 hour in horses with colonic venous obstruction and was characterized by inter- and intracellular edema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456540 TI - Evaluation of clinical signs of disease, bronchoalveolar and tracheal wash analysis, and arterial blood gas tensions in 13 horses with chronic obstructive pulmonary disease treated with prednisone, methyl sulfonmethane, and clenbuterol hydrochloride. AB - We evaluated the efficacy of 3 treatments for chronic obstructive pulmonary disease in horses: prednisone (400 mg/horse, PO, daily; n = 7), methyl sulfonmethane (10 g/horse, PO, q 12 h; n = 6), and clenbuterol hydrochloride (0.4 mg/horse, PO, q 12 h; n = 7). A fourth group acted as controls (n = 6) and was not treated. The treatment period lasted 10 days. Each horse was a member of 2 different groups for 10 days, separated by an 18-day interval of no treatment. All horses were housed together in an outdoor pen without bedding. Horses were fed alfalfa/grass hay mix ad libitum from a large feeder. The same batch of hay was fed throughout the study. Multiple physical and laboratory variables were monitored prior to, during, and at the end of each 10-day trial period. Changes in lung sounds, respiratory effort, degree of anal movement, nasal discharge, temperature, respiratory rate, or heart rate were not significant. Changes in arterial blood gas tensions, tracheal wash or bronchoalveolar lavage cytologic findings, or phagocyte function were not significant. All horses were tachypneic and most were tachycardic. The median value for PaO2 was below normal for all horses. All tracheal wash and most bronchoalveolar lavage cytologic findings represented a suppurative response. Negative linear correlation was observed between PaO2 and degree of respiratory effort in these horses (eg, as PaO2 decreased, the degree of respiratory effort increased). PMID- 1456542 TI - Bromodeoxyuridine labeling and DNA content of pulmonary arterial medial cells from hypoxia-exposed and nonexposed healthy calves. AB - Vascular medial thickening is a prominent finding in people and animals with refractory neonatal pulmonary hypertension. Smooth muscle cells are capable of 2 distinct growth responses in vivo: hypertrophy or hyperplasia. Hypertrophic smooth muscle cells may undergo DNA synthesis without cell division, leading to a polyploid state. To better understand the nature of smooth muscle cell growth in healthy and pulmonary hypertensive neonatal calves, we measured incorporation of the thymidine analog bromodeoxyuridine (BrdUrd) and total DNA content in medial cells from control (pulmonary arterial pressure = 32 +/- 2 mm of Hg) and hypobaric hypoxia-exposed (pulmonary arterial pressure = 120 +/- 7 mm of Hg) calves. Labeling of medial cells with BrdUrd measured by flow cytometry was increased (P < 0.02) in pulmonary arteries of hypoxia-exposed calves (n = 5), compared with control calves (n = 5). Immunohistochemical localization of BrdUrd indicated that BrdUrd labeling of large elastic pulmonary arteries from hypoxia exposed calves was increased almost exclusively in the outer half of the medial wall. Increased BrdUrd labeling of muscular pulmonary arteries from hypoxia exposed calves was observed in the arterial media and adventitia, and tended to exit in clusters. Analysis of DNA content by flow cytometry indicated a decrease (P < 0.05) in percentage of tetraploid medial cells in pulmonary arteries from hypoxia-exposed calves, compared with control calves. Bivariate analysis for BrdUrd labeling and DNA content of cells from the pulmonary arteries of hypoxia exposed calves indicated a subpopulation of diploid cells with positive BrdUrd labeling, suggestive of DNA synthesis and subsequent cell division.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456543 TI - Retrospective evaluation of factors associated with the risk of seropositivity to Ehrlichia risticii in horses in New York State. AB - A retrospective study was designed to determine the distribution of equine monocytic ehrlichiosis among the equine population in New York state, and to identify factors associated with risk of disease. Serum samples submitted to the diagnostic laboratory of the university during the period from January 1985 through December 1986 were examined for antibodies to Ehrlichia risticii, using the indirect fluorescent antibody technique. Factors evaluated included geographic origin and date of submission of the sample, and age, breed, and sex of the horse. Logistic regression analysis was used to identify which factors were significantly associated with the risk of seropositivity to E risticii, while simultaneously controlling for other factors. Of the 2,579 tested samples, 1,950 (76%) had positive results. Factors significantly associated with risk of seropositivity to E risticii were: breed of the horse (Thoroughbreds were 3 times more likely to have been exposed to E risticii, compared with non-Standardbred, non-Thoroughbred breeds); sex (female horses were 2.7 times more likely to have been exposed, compared with male horses); age of the horse (the risk of being exposed to E risticii increased with age, peaked at around 12 years, and decreased thereafter); and month of submission (horses tested during November and December had the highest odds of being seropositive [odds ratio = 2.1], and horses tested during March through April were least likely to be seropositive [odds ratio = 0.5], compared with horses tested during January and February). PMID- 1456544 TI - Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy beagles. AB - The small intestine of healthy adult Beagles was examined to determine whether subclinical abnormalities might exist that would be relevant to the use of Beagles in pharmacologic studies. Duodenal juice was obtained for qualitative and quantitative bacteriologic examinations; jejunal mucosa was taken for morphologic and biochemical investigation, and intestinal permeability was assessed by quantification of 24-hour urinary excretion of 51Cr-labeled EDTA after its oral administration. Comparisons were made with findings in healthy adult dogs of other breeds that served as controls. Small intestinal bacterial overgrowth was found in 14 of the 21 Beagles examined, and represented a mixed flora that included obligate anaerobic bacteria in 8 dogs and exclusively aerobic bacteria in 6 dogs. Intestinal permeability (percentage urinary recovery of 51Cr-labeled EDTA; mean +/- SEM) was considerably higher (P < 0.01) in Beagles with anaerobic overgrowth (37.6 +/- 3.2%) or aerobic overgrowth (30.5 +/- 4.8%), compared with Beagles with no overgrowth (17.3 +/- 1.6%) and with controls (11.1 +/- 1.0%). In Beagles, significant (r = 0.54, P = 0.03) correlation was observed between 24 hour urinary recovery of 51Cr-labeled EDTA and bacterial numbers in duodenal juice. Morphologic changes in jejunal mucosa were minimal, and specific activities of brush border enzymes were not significantly decreased, apart from aminopeptidase N, but activities of lysosomal and endoplasmic reticular marker enzymes were higher in the 3 groups of Beagles with anaerobic, aerobic, or no overgrowth, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456545 TI - Effect of protein source in liquid formula diets on food intake, physiologic values, and growth of equine neonates. AB - The effects of 2 liquid formula diets differing in protein source were evaluated in orphan foals. The response of 7 foals fed a diet containing casein as the protein source, and 6 foals fed a diet containing a combination of whey and casein, was compared with the response in a reference group of 8 mare-raised foals. Orphaned foals were fed 150 kcal/kg of body weight/d, divided into 6 equal feedings of 25 kcal/kg. Formula intake was comparable among the experimental groups, and foals fed the liquid formula diet grew as well as mare-raised foals. There was no difference among groups in mean daily body weight gain, wither height, heart girth, body temperature, pulse, respiration rate, capillary refill time, or skin tenting. Insulin and blood glucose concentrations increased in both groups of foals fed formula diets, returning to prefeeding values within 4 hours. Differences among groups were found for serum alkaline phosphatase, alanine transaminase, cholesterol, creatinine, and glucose values; all other serum chemical values were comparable among groups. Plasma amino acid determinations revealed that arginine and ornithine were significantly lower in foals in both experimental groups than in reference foals, suggesting that arginine may have been the limiting amino acid in these diets. Diarrhea developed in foals in all treatment groups, but in most cases was self-limiting. These results suggest that the protein source of liquid formula diets may be less important in foals than in infants. PMID- 1456546 TI - Malabsorption of vitamin A in preruminating calves infected with Cryptosporidium parvum. AB - Serum retinol, retinyl palmitate, and total vitamin A concentrations, and jejunoileal morphology were examined in neonatal calves infected with Cryptosporidium parvum. Group-1 calves served as noninfected controls and, after an adjustment period, were given 50 ml of saline solution i.v. every 12 hours for 6 days. Group-2 calves were inoculated with 10(7) C parvum oocysts and, after the onset of diarrhea, were given 50 ml of saline solution i.v. every 12 hours for 6 days. Group-3 calves were inoculated with 10(7) C parvum oocysts and, after the onset of diarrhea, were treated with difluoromethylornithine (DFMO, 200 mg/kg of body weight i.v., q 12 h) for 6 days. Group-4 calves were naturally infected with C parvum. Jejunoileal biopsy specimens were excised from calves of groups 1-3 at 3 and again at 15 to 16 days of age. During the course of diarrhea and 3 days after saline or DFMO administration, water-miscible retinyl palmitate was administered orally (2,750 micrograms/kg) to each calf in each group. Cryptosporidium parvum infection was associated with significant (P < or = 0.05) reduction in postadministration serum retinol, retinyl palmitate, and total vitamin A concentrations in calves of groups 2, 3, and 4. Cryptosporidium parvum infection caused significant (P < or = 0.05) reduction in villus height. Decreased villus height, villus blunting and fusion, and attenuation of the intestinal mucosa were associated with reduced absorption of vitamin A, as indicated by lower peak postadministration retinyl palmitate concentration in C parvum-infected calves. Intravenous administration of DFMO to group-3 calves did not improve retinol absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456547 TI - Bronchoscopy of the horse. AB - The endobronchial anatomy of 12 lung specimens from horses and 12 healthy, standing, sedated horses was evaluated, using a 200-cm-long, 9.5-mm-diameter videoendoscope. On the basis of these findings, the nomenclature system of Amis and McKiernan was modified for identification of airways of horses during bronchoscopy. Lobar bronchi are identified on the basis of the side of the bronchial tree on which they were found and the order in which they originated from the primary bronchus. Thus, RB1, RB2, and RB3 referred to right cranial lobar bronchus, respectively. On the left side, the designation of LB1 and LB2 refer to the left cranial lobar bronchus and the left caudal lobar bronchus, respectively. Segmental bronchi are identified by consecutive numbers in the order of origination from the lobar bronchus. The direction of the segmental bronchus was denoted by the capital letter D (dorsal), V (ventral), L (lateral), M (medial), R (rostral), and C (caudal). Subsegmental bronchi were identified in the order of origination from the segmental bronchi, using lower case letters (eg, RB2, 1V, a or RB2, 1V, aV). For subsequent branching of the subsegmental bronchi, the branches were numbered consecutively by their order of origination (eg, RB2, 1V, aV, 1D). PMID- 1456548 TI - Gastric emptying of nondigestible radiopaque markers after circumcostal gastropexy in clinically normal dogs and dogs with gastric dilatation-volvulus. AB - Using radiopaque particles mixed with food, gastric emptying was assessed in healthy dogs not subjected to surgery, in healthy dogs 9 to 35 days after circumcostal gastropexy, and, in dogs 1 to 54 months after surgical treatment and recovery from gastric dilatation-volvulus (GDV). Circumcostal gastropexy surgery did not alter the 90% gastric emptying time for radiopaque particles in healthy dogs. However, 90% gastric emptying time was significantly (P less than 0.05) increased after circumcostal gastropexy in dogs with GDV, compared with healthy dogs after the same surgical procedure and recovery period. These results imply that dogs with GDV have delayed gastric emptying of solid particles. Whether delayed gastric emptying of markers detected in affected dogs after surgical treatment and recovery was the result or the cause of GDV was not determined. Results indicate that circumcostal gastropexy could be recommended as a prophylactic procedure for GDV in large breeds with deep thorax, because delayed gastric emptying of markers secondary to the surgical procedure is unlikely. PMID- 1456549 TI - Immunotoxicity of ochratoxin A to growing gilts. AB - Ochratoxin A (OA) was incorporated in the diets of growing gilts (mean body weight, 20.1 kg) at a concentration of 2.5 mg of OA/kg of feed and was fed continuously for 35 days. Humoral and cell-mediated immunologic measurements were evaluated to determine the effects of OA on immune function in swine. Cutaneous basophil hypersensitivity to phytohemagglutinin (PHA), delayed hypersensitivity to tuberculin, PHA-induced lymphocyte blastogenesis, interleukin-2 production, total and isotype immunoglobulin concentrations, antibody response to chicken RBC, and macrophage activation were used to evaluate immune function. Gilts treated with OA had reduced cutaneous basophil hypersensitivity response to PHA, reduced delayed hypersensitivity to tuberculin, decreased stimulation index for lymphoblastogenesis, decreased interleukin-2 production when lymphocytes were stimulated with concanavalin A, and decreased number and phagocytic activity of macrophages. Differences were not observed for total and isotype immunoglobulin concentrations, or humoral hemagglutination (chicken RBC) titer. These data indicate that OA may suppress cell-mediated immune response in growing swine. PMID- 1456550 TI - Patient compliance. Are we wasting our time and don't know it? PMID- 1456551 TI - The effect of hyperinflation on rib cage-abdominal motion. AB - Abnormalities of rib cage-abdominal motion are common in patients with chronic obstructive pulmonary disease (COPD), but the basis of the abnormal motion has not been completely determined. Although airway obstruction has been shown to be a major factor in causing abnormal chest wall motion, the effect of hyperinflation (which has numerous adverse effects on respiratory muscle function) has not been systematically examined. We induced graded levels of hyperinflation in six healthy volunteers using continuous positive airway pressure (CPAP) levels of 10, 20, and 30 cm H2O. Chest wall motion was measured by a calibrated inductive plethysmograph. Rib cage-abdominal asynchrony and paradox were quantitated by the Konno-Mead method of analysis. CPAP levels of 10, 20, and 20 cm H2O produced increases in end-expiratory lung volume of 0.98 +/- 0.14 (SE), 1.90 +/- 0.31, and 2.42 +/- 0.37 L, respectively (p < 0.0001). This corresponded to an increase in the ratio of functional residual capacity to predicted total lung capacity from 0.38 +/- 0.08 at baseline to 0.74 +/- 0.14 at 30 cm H2O CPAP-comparable to that seen in patients with COPD. Hyperinflation induced an increase in inspiratory abdominal paradox, 1.0 +/- 0.7% at baseline versus 3.6 +/- 1.7% at 30 cm H2O (p < 0.05), but this is unlikely to be clinically significant. A significant increase in asynchrony or rib cage paradox did not develop with hyperinflation. In conclusion, the primary factor contributing to abnormal chest wall motion in patients with COPD is likely to be increased airway resistance, and hyperinflation makes only a minor contribution. PMID- 1456552 TI - Effect of chronic renal failure on skeletal and diaphragmatic muscle contraction. AB - The changes in muscle mechanical properties caused by the myopathy of chronic uremia was examined in the soleus and the diaphragm muscles of rats in which chronic uremia was produced by subtotal nephrectomy. Using an in vitro muscle preparation in two groups of rats (moderately and severely uremic), we determined that uremia had a significant detrimental effect on both muscles with respect to the force-frequency relationships. In the diaphragm it decreased by 15% in the moderate group and by 43% in the severe group. In the soleus it decreased by 20% in both groups. Twitch characteristics behaved differently in the soleus and the diaphragm muscles in that 1/2 RT and TPT increased significantly (p < 0.05) in the soleus (severely uremic group) but not in the diaphragm. Fatigability was increased in both muscles in the moderately uremic rats and in the diaphragm in the severely uremic rats; however, the fatigability of the soleus in the severely uremic group was not different from that in the control group. Our findings suggest that the myopathic changes occurring in chronic uremia affects the function of the soleus and the diaphragm in different ways. Other findings in the severely uremic group indicate that additional factors such as marked electrolyte imbalances may also affect the excitation-contraction coupling in different ways. PMID- 1456553 TI - Androgen blockade does not affect sleep-disordered breathing or chemosensitivity in men with obstructive sleep apnea. AB - As sleep apnea is more prevalent in men and testosterone has known effects on sleep apnea and chemosensitivity, reduction of androgen activity may influence sleep-disordered breathing and respiratory control. We studied the effect of 1 wk of treatment with flutamide, a nonsteroidal antiandrogen, on sleep, respiration, and ventilatory control in eight men with sleep apnea. Results on flutamide were compared with two baseline studies performed before and after the drug treatment period. Although effective androgen blockade was achieved as evidenced by increased hormone levels, flutamide had no effect on sleep architecture or chemoresponsiveness to hypoxia and hypercapnia. There was a trend towards a reduction in respiratory disturbance index in both NREM and REM sleep (41 +/- 4 baseline versus 34 +/- 3 flutamide, p = 0.09 NREM; 53 +/- 4 baseline versus 48 +/ 3 flutamide, p = 0.16 REM), but this was not significant. Our results indicate that androgen blockade had no clinically significant effect on sleep, sleep disordered breathing, or chemosensitivity in patients with moderate to severe sleep apnea. More specific blockers such as gonadotrophin-releasing hormone analogs may have more clinical effect or, alternatively, androgen blockade may be more beneficial in patients with milder sleep apnea. PMID- 1456554 TI - Size and mechanical properties of the pharynx in healthy men and women. AB - Obstructive sleep apnea (OSA) has a marked male predominance. To determine whether there are differences in the mechanical properties of the pharynx of men and women that may contribute to the gender difference in disease incidence, we measured pharyngeal cross-sectional area during quiet breathing in 77 normal men and 98 normal women using the acoustic pulse technique. Standard pulmonary function tests were also performed. Pharyngeal mechanics were studied in 23 men and 34 women by measuring the change in pharyngeal area during a slow vital capacity maneuver. Gender was found to be the most important independent factor contributing to pharyngeal size. The men had a significantly larger pharynx than the women (3.63 +/- 0.10 versus 3.20 +/- 0.09 cm2, mean +/- SEM; p < 0.01). Pharyngeal mechanics were also different between men and women. The men had a larger change in pharyngeal area with changing lung volume than the women (0.60 +/- 0.14 versus 0.12 +/- 0.12 cm2, mean +/- SEM; p < 0.02). This difference persisted even after normalizing the data for pharyngeal size. We found that there are gender-related differences in the size and mechanical properties of the pharynx and speculate that the larger pharynx of men may be more than offset by greater changes in pharyngeal size with changing lung volume, contributing to the greater incidence of OSA in men. PMID- 1456555 TI - Theophylline does not increase ventilatory responses to hypercapnia or hypoxia. AB - Theophylline is commonly believed to stimulate central respiratory centers. We studied the effect of oral theophylline therapy on ventilatory responses to hypercapnia and hypoxia during a double-blind placebo-controlled trial with a slow release oral theophylline preparation. We measured hypercapnic and hypoxic ventilatory responses using rebreathing techniques in 15 subjects (21 to 41 yr of age, with normal lung function) on three occasions: baseline, after 4 days of Drug 1, and after 4 days of Drug 2. For subjects receiving theophylline, the mean serum theophylline level was 11.3 + 1.3 (SE) micrograms/ml (range, 5.3 to 22.1). Unpleasant side effects were reported by 11 of the 15 subjects (nausea, jitteriness, and agitation) while receiving theophylline but not while receiving placebo. The mean hypercapnic ventilatory response with placebo was 4.3 +/- 0.9 L/min/mm Hg PACO2 and with theophylline it was 4.5 +/- 0.7 L/min/%SaO2 and with theophylline it was -2.7 +/- 0.4 L/min/%SaO2. Hypoxic responses for each subject were measured at similar PvCO2. There were no significant changes in ventilatory responses with theophylline. We conclude that theophylline use, at a dose sufficient to cause side effects, does not affect chemoreceptor responsiveness. PMID- 1456556 TI - Effects of repetitive airway obstruction on O2 saturation and systemic and pulmonary arterial pressure in anesthetized dogs. AB - We examined the effects of multiple repetitive airway obstruction (RAO) on arterial oxygen saturation (SaO2) and pulmonary and systemic arterial pressure in eight anesthetized spontaneously breathing dogs. SaO2 was monitored at the tongue with a pulse oximeter. RAO created by an electrical valve that was attached to a tracheal cannula was alternated with seven consecutive spontaneous breaths until the nadir SaO2 (nSaO2) became constant or decreased to less than 35%. Tracheal occlusion durations of 15, 30, 45 and 60 s were chosen arbitrarily. In each animal nSaO2 decreased with every trial number in an exponential fashion, and the rate of nSaO2 fall was greater for the longer occlusion duration. In each animal the increases in pulmonary arterial pressure (PAP) and systemic arterial pressure (SAP) were inversely related to the nSaO2 values, and the relationship between nSaO2 and PAP or SAP was identical for all occlusion durations. Moreover, when the animals breathed pure oxygen and SaO2 did not decrease, there were no significant increases in the PAP and SAP at similar levels of pleural pressure (Ppl). In another six dogs, the effects of RAO on PAP and SAP were compared with those of intermittent hypoxic exposure without apnea, which was achieved by the inhalation of hypoxic gas (4 to 6% O2, 5% CO2 in N2) instead of RAO, to examine the effects of interruption of ventilation. The relationships between nSaO2 and both pressures did not differ significantly from those during RAO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456557 TI - Tracheal gas insufflation during pressure-control ventilation. Effect of catheter position, diameter, and flow rate. AB - In the setting of acute lung injury, ventilatory strategies that adjust minute ventilation (VE) to achieve eucapnia often lead to alveolar rupture or damage. Tracheal gas insufflation (TGI) reduces the VE requirements of conventional mechanical ventilation by decreasing the effective dead-space fraction (VD/VT) of each breath. We studied the effect of catheter flow rate (Vcath) and position as well as catheter tip diameter and configuration on CO2 elimination during TGI augmented pressure-controlled ventilation (PCV) in normal dogs. We studied three catheter positions (1, 5, and 10 cm above the carina) at Vcath of 2, 5, and 10 L/min (n = 6). When the catheter tip was positioned 1 cm above the carina, PaCO2 decreased significantly from a baseline (PCV alone) of 67 +/- 10 mm Hg to 52 +/- 11, 43 +/- 9, and 32 +/- 7 mm Hg (p < 0.05) at Vcath of 2, 5, and 10 L/min, respectively. For the same Vcath values, positioning the catheter tip 10 cm above the carina increased PaCO2 to 54 +/- 15, 46 +/- 12, and 40 +/- 11 mm Hg. Advancing the catheter tip 2 cm below the carina did not improve PaCO2 significantly (n = 3). At a catheter position of 1 cm above the carina and a Vcath of 10 L/min, changing the luminal inner diameter (1.5 versus 3.0 mm) or tip configuration (open tip versus occluded tip with two side holes) of the catheter did not change PaCO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456558 TI - HIV-1 envelope protein (gp120) inhibits the activity of human bronchoalveolar macrophages against Cryptococcus neoformans. AB - Cryptococcus neoformans infections are a major cause of morbidity and mortality for HIV-infected persons. Containment of the initial respiratory inoculation to the lung appears defective in patients with AIDS despite the low burden of HIV in bronchoalveolar macrophages. We have studied the fungistatic activity of human bronchoalveolar macrophages (BAM) cultured with an encapsulated strain of C. neoformans in the presence of pooled human serum. We observed 51.6% fungistasis after 24 h of culture. Fungistasis was diminished if the pooled human serum was heat-inactivated but was not affected by anticryptococcal capsular IgG. HIV envelope protein (gp120) has been shown to interfere with lymphocyte activation in vitro. We studied the effects of gp120 on BAM function and found that fungistatic activity was inhibited 25% (p < 0.001). Although binding of yeasts was not affected, gp120 inhibited the internalization of bound yeasts by 46% (p = 0.025). These experiments indicate that gp120 decreases the internalization and fungistasis of C. neoformans by human BAM, and they suggest a mechanism to explain how a small number of HIV-1-infected cells in the lung could impair the containment of C. neoformans. PMID- 1456559 TI - Two-year incidence of tuberculosis in cohorts of HIV-infected and uninfected urban Rwandan women. AB - To determine the prevalence of Mycobacterium tuberculosis infection and the incidence of tuberculosis in HIV-infected and uninfected urban Rwandan women, 460 HIV-positive and 998 HIV-negative childbearing women were recruited from pediatric and prenatal care clinics and were enrolled in a prospective study in 1988 and followed for 2 yr. Tuberculin testing was administered 12 to 18 months after enrollment. Fifty-three percent of HIV-negative women had positive tuberculin tests (induration > or = 10 mm), with higher rates among older women and among women who had received BCG vaccine. Only 21% of HIV-positive women had positive tuberculin tests, with no relationship to BCG vaccine. Follow-up was available for 93% of subjects. Tuberculosis was diagnosed in 20 HIV-positive women and in two HIV-negative women. Features associated with an increased risk of tuberculosis among HIV-positive women included: age > or = 30, body mass index in the lowest quartile, low income, erythrocyte sedimentation rate > 75, positive tuberculin test, and chronic cough, chronic fever, and weight loss. Among Rwandan women who are infected with HIV, approximately half of those who are infected with M. tuberculosis do not have positive tuberculin tests. The rate ratio for development of tuberculosis among HIV-positive women was 22 (95% CI, 5 to 92). New algorithms are needed to improve the early detection of tuberculosis among HIV-positive patients in Africa. PMID- 1456560 TI - The combined effect of rifampin and pyrazinamide within the human macrophage. AB - A recent study in the murine model suggested that a combination of rifampin and pyrazinamide used as preventive therapy might shorten the duration of treatment time. Clinical trials using this combination have been initiated, but significant results will not be available for many years. The ex vivo human macrophage model has been instructive in expanding our knowledge of the activity of chemotherapeutic agents against intracellular virulent tubercle bacilli. Prior studies have shown rifampin to have a bactericidal effect in this model while even at clinically unachievable levels, pyrazinamide had only a bacteriostatic impact. This study finds an enhanced bacteriostatic effect when low, nonbactericidal levels of rifampin are combined with clinically achievable levels of pyrazinamide but not with higher bactericidal levels of rifampin. Adding pyrazinamide 2 days after the introduction of rifampin clearly enhanced the combined killing effect. However, reversing the order and adding rifampin 2 days after the introduction of pyrazinamide produced a result weaker than introducing the agents simultaneously. Our findings do not support the use of these agents as a potentially effective preventive therapy combination, but they suggest that the timing of the administration of these chemotherapeutic agents could be an important factor in their effectiveness. PMID- 1456561 TI - Oxygen-induced lung damage. Relationship to lung mitochondrial glutathione levels. AB - Several reports suggest there is a relationship between lung glutathione (GSH) levels and susceptibility to oxygen-induced lung damage. However, studies of other organs and cells indicate that a better relationship may exist between mitochondrial GSH levels and oxidant damage. We determined whether there is a similar relationship in the lung using a well-characterized mouse model and a series of interventions that alter lung GSH levels and susceptibility to oxygen induced lung damage. Mice were fasted or given buthionine sulfoximine (BSO, 20 mM), which reduce total lung GSH levels and increase susceptibility to oxygen induced lung damage. Mice were also given glutathione monoethyl ester (GSH-ME) intraperitoneally (5 or 10 mM/kg/day for 2 days) or intratracheally (0.2 mM once) in an attempt to increase lung GSH levels. Fasting for up to 3 days and the administration of BSO for 7 to 10 days decreased total lung GSH levels (p < 0.001 for both) but not lung mitochondrial GSH levels. Intraperitoneal administration of GSH-ME increased mitochondrial GSH levels (p < 0.001 in both fed and fasted mice), but it had little effect on total lung GSH levels and no effect on susceptibility to oxygen-induced lung damage. Exposure to 100% oxygen increased mitochondrial GSH levels in both the fed and fasted mice to nearly the same extent (p < 0.001 for both). However, the fasted mice had lower total lung GSH levels compared with the fed mice (p < 0.05) and increased susceptibility to 100% oxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456562 TI - The effect of smoke inhalation on lung function and airway responsiveness in wildland fire fighters. AB - The current study was undertaken to evaluate the effect of smoke on forced expiratory volumes and airway responsiveness in wildland fire fighters during a season of active fire fighting. Sixty-three seasonal and full-time wildland fire fighters from five U.S. Department of Agriculture Forest Service (USDAFS) Hotshot crews in Northern California and Montana completed questionnaires, spirometry, and methacholine challenge testing before and after an active season of fire fighting in 1989. There were significant mean individual declines of 0.09, 0.15, and 0.44 L/s in postseason values of FVC, FEV1, and FEF25-75, respectively, compared with preseason values. There were no consistent significant relationships between mean individual declines of the spirometric parameters and the covariates: sex, smoking history, history of asthma or allergies, years as a fire fighter, upper/lower respiratory symptoms, or membership in a particular Hotshot crew. There was a statistically significant increase in airway responsiveness when comparing preseason methacholine dose-response slopes (DRS) with postseason dose-response slopes (p = 0.02). The increase in airway responsiveness appeared to be greatest in fire fighters with a history of lower respiratory symptoms or asthma, but it was not related to smoking history. These data suggest that wildland fire fighting is associated with decreases in lung function and increases in airway responsiveness independent of a history of cigarette smoking. Our findings are consistent with the results of previous studies of municipal fire fighters. PMID- 1456563 TI - Dust- and endotoxin-related respiratory effects in the animal feed industry. AB - A cross-sectional study of 315 animal feed workers was undertaken in 14 animal feed mills in the Netherlands. Primary aims were to explore relationships between exposure to organic dust and respiratory symptoms and chronic lung function changes. The study comprised monitoring dust and endotoxin exposure, spirometric lung function measurements (FVC, FEV1, mean midexpiratory flow, and flow-volume parameters) and a questionnaire for respiratory symptoms. The exposure was measured in two periods, during spring and autumn. The average 8-h personal inspirable dust exposure was 9 mg/m3 grain dust (range, 0.2 to 150 mg/m3) and 25 ng/m3 endotoxin (range, 0.2 to 470 ng/m3) based on 530 personal dust measurements. On the basis of these measurements and the occupational history of the workers, the number of years "worked in dust" and an estimate of the cumulative dust and endotoxin exposure were calculated. The prevalence of most chronic respiratory symptoms tended to decrease with increasing years of exposure. The "healthy worker effect" is probably responsible for this finding. In general, a strong negative association between most of the exposure variables and lung function was found. The endotoxin exposure was more strongly related to decreases in lung function than the dust exposure. The estimated effects of an average (cumulative) endotoxin exposure on lung function were greater, with a higher statistical significance, than for an exposure to dust. These results suggest that endotoxin exposure is an important factor in the development of respiratory impairment. The lung function changes occur at endotoxin levels ranging from 0.2 to 470 ng/m3. PMID- 1456564 TI - Exposures of older adults with chronic respiratory illness to nitrogen dioxide. A combined laboratory and field study. AB - We combined field and laboratory experimentation to evaluate the effects of nitrogen dioxide in a panel of Los Angeles area residents with chronic respiratory illness, 15 men and 11 women aged 47 to 69. All had heavy smoking history, chronic symptoms, and low FEV1; some also had low FVC. During the fall winter high-NO2 season, they monitored themselves for 2-wk periods using spirometers in the home, passive NO2 sampling badges, and diaries to record time and activity patterns and clinical status. In the middle of each self-monitoring week they were exposed in a chamber, once to clean air and once to 0.3 ppm NO2. Chamber exposures were double blind, lasted 4 h, and included four 7-min exercise sessions with average ventilation rates near 25 L/min. Symptom reports and hourly forced expiratory function tests showed no statistically significant differences between clean air and NO2 chamber exposures, although peak flow showed a approximately 3% loss with NO2 relative to clean air during the first 2 h of exposure only (p = 0.056). No significant overall differences were found between field self-measurements and measurements of lung function in the chamber or between field measurements in clean air and NO2 exposure weeks. Field data showed that group average lung function and symptom levels were worse in the morning than later in the day (p < 0.005) but otherwise were stable over 2 wk. Even though most subjects smoked and stayed indoors 80 to 90% of the time, personal NO2 exposures correlated significantly with outdoor NO2 concentrations as reported by local monitoring stations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456565 TI - Effects of steady-state and variable ozone concentration profiles on pulmonary function. AB - Measurements of ambient ozone (O2) concentration during daylight hours have shown a spectrum of concentration profiles, from a relatively stable to a variable pattern usually reaching a peak level in the early afternoon. Several recent studies have suggested that in estimating exposure dose (O3 concentration [C] x exposure time [T] x ventilation [V]), O3 concentration needs to be weighted more heavily than either ventilation or duration of exposure in the estimates. In this study we tested the hypothesis that regardless of concentration pattern and exposure rate the same exposure dose of O3 will induce the same spirometric response. We exposed 23 healthy male volunteers (20 to 35 yr of age) for 8 h to air, 0.12 ppm O3 (steady-state), and a triangular exposure pattern (concentration increased steadily from zero to 0.24 ppm over the first 4 h and decreased back to zero by 8 h). During the first 30 min of each hour, subjects exercised for 30 min at minute ventilation (VE) approximately 40 L/min. The order of the exposures was randomized, and the exposures were separated by at least 7 days. The response patterns over the 8-h periods for spirometric variables in both O3 exposures were statistically different from air exposure changes and from each other. For FEV1 the p values were 0.017 between air and steady-state profile, 0.002 between air and triangular profile, and 0.037 between steady-state and triangular profiles. Although in the triangular pattern of exposure the maximal O3 concentration was reached at 4 h, the maximum FEV1 decrement (10.2%) was observed at 6 h of exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456566 TI - Risk factors for increased airway responsiveness to methacholine challenge among laboratory animal workers. AB - As a first step in a prospective study of the incidence of asthma to laboratory animals, a group of 364 adults 18 to 48 yr of age who were beginning employment with laboratory animals were evaluated in terms of their past history, health status, allergy, and airway responsiveness to methacholine. At entry to the study, 269 had previous occupational contact with animals, 109 had chest symptoms in the previous year, 168 had a history of allergic symptoms to laboratory animals (any with asthmatic responses were systematically excluded), and 118 had positive immediate skin tests (29 had positive skin tests to laboratory animals). When defined as a PD20FEV1 of 80 breath units or less, 18.4% of these young adults had methacholine hyperresponsiveness (HRA). Significant risk factors for HRA were found to be younger age, female sex, lower educational level, a history of allergic symptoms to laboratory animals, and a history of chest symptoms. Positive skin tests to laboratory animals were present in 8% of workers; this was not a significant risk factor for HRA although positive skin tests to pollen and household allergens were. Previous work experience was a risk factor, especially among those with allergic symptoms, and a trend toward self-selection was suggested in that the rate of HRA was lowest in workers with more than 2 yr of experience or with two or more previous jobs with laboratory animals. PMID- 1456567 TI - Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma. AB - To partition the central and peripheral airway resistance, a catheter-tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus with a 3 mm inner diameter in 10 patients with asymptomatic asthma. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by subtraction of RC from RL. Therefore, our measurement of Rp included lung tissue resistance. The technique permitted identification of the site of changes in airway resistance. The baseline values of resistances were 2.3 +/- 0.2 cm H2O/L/s in RL, 1.5 +/- 0.1 cm H2O/L/s in RC, and 0.8 +/- 0.1 cm H2O/L/s in Rp, respectively. To determine the site of airway hyperresponsiveness, dose-response curves of central, peripheral, and total airways to inhaled methacholine were separately constructed. Bronchial responsiveness was evaluated by a log methacholine unit requiring a 35% decrease (PC35) and a 50% decrease (PC50) in pulmonary conductance (a reciprocal of RL). We calculated the increase of resistances in total (delta RL), central (delta RC), and peripheral (delta Rp) airways from the baseline values at either PC35 or PC50.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456568 TI - Physiologic effects of oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. A randomized control study. AB - The association between severe nutritional depletion and chronic obstructive pulmonary disease (COPD) has long been recognized. A potential therapeutic benefit to nutritional support was previously suggested by us in a pilot investigation. Subsequent studies have reported conflicting results regarding the role of nutritional therapy in this clinical population. We report a randomized controlled study of nutritional therapy in underweight patients with COPD that combines an initial inpatient investigation (controlled nutritional support) with a prolonged outpatient follow-up interval. Provision of adequate calorie and protein support, adjusted to metabolic requirements, resulted in weight gain (intervention = +2.4 kg versus control -0.5 kg), improved handgrip strength (intervention = +5.5 kg-force versus control -6.0 kg-force), expiratory muscle strength (intervention = +14.9 cm H2O versus control -9.2 cm H2O), and walking distance (intervention = +429 feet versus control -1.0 foot). Inspiratory muscle strength was also improved (intervention = +11.4 cm H2O versus control +4.8 cm H2O) although this did not quite reach statistical significance. We conclude that provision of adequate nutrient supply under controlled conditions results in significant clinical improvements in the COPD patient population. However, the intervention is costly, time-intensive, and of limited therapeutic magnitude. More detailed work of alternative outpatient strategies combined with additional rehabilitative measures is indicated to delineate the full therapeutic potential of nutritional support for this clinical population. PMID- 1456569 TI - Acetazolamide and furosemide attenuate asthma induced by hyperventilation of cold, dry air. AB - We investigated the assumption that the efficacy of inhaled diuretics in asthma is dependent upon inhibition of the Na+/K+/2Cl- cotransporter. We compared the protective effect of acetazolamide, a diuretic without significant effect on the loop cotransporter, with the protection provided by inhaled furosemide in a cold, dry air hyperventilation model of asthma. Seven asthmatic subjects underwent a baseline bronchial challenge and then received a nebulized dose of 80 mg of furosemide or 500 mg of acetazolamide or saline placebo in a randomized, double blind, placebo-controlled crossover design. Repeat challenges were performed immediately and at 2 and 4 h postnebulization. Acetazolamide caused a 47.2% increase in the amount of cold, dry air required to reduce the FEV1, by 20% (expressed in terms of respiratory heat loss as PD20RHL), from 0.79 multiplied or divided by (x/divided by) 1.13 kcal/min (geometric mean x/divided by geometric SEM) at baseline to 1.17 x/divided by 1.09 kcal/min postnebulization (p < 0.025). Furosemide increased the geometric mean PD20RHL by 53.9%, from 0.86 x/divided by 1.12 kcal/min to 1.33 x/divided by 1.12 kcal/min (p < 0.001). There was no significant change after placebo inhalation (0.81 x/divided by 1.15 kcal/min versus 0.87 x/divided by 1.10 kcal/min, NS). Airway responsiveness had returned to baseline by 2 h postnebulization on all 3 days. Furosemide also caused bronchodilatation, producing a 14.1% rise in the mean FEV1 (p < 0.005 versus prenebulization), whereas neither acetazolamide nor placebo altered airway tone significantly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456570 TI - Timing of prednisone and alterations of airways inflammation in nocturnal asthma. AB - Asthmatic subjects prone to nocturnal worsening demonstrate overnight recruitment of inflammatory cells into the airways. The influence of dose timing on the ability of corticosteroids to block circadian recruitment of inflammatory cells into asthmatic airways and attenuate the nocturnal worsening of asthma is unclear. In a double-blind, placebo-controlled, crossover design, we evaluated the response of seven asthmatic subjects with respect to overnight spirometry, blood eosinophil counts, and bronchoalveolar lavage cytology to a single variably timed 50 mg oral dose of prednisone given at 0800, 1500, or 2000 h. Compared to placebo, a single prednisone dose at 1500 h resulted in a reduction in the overnight percentage fall in FEV1 (-28.2 +/- 7.3 versus -10.4 +/- 4.5%, p = 0.04) and improvement in the 0400 h FEV1 (2.53 +/- 0.38 versus 3.43 +/- 0.38 L, p = 0.03). In contrast, neither a 0800 nor 2000 h prednisone dose compared to placebo resulted in overnight spirometric improvement. Also following the 1500 h prednisone dose, blood eosinophil counts were significantly reduced at both 2000 and 0400 h. Lastly, the 1500 h dosing resulted in a pan-cellular reduction in bronchoalveolar lavage cytology (p < or = to 0.05 for all cell lines compared to placebo), but neither alternative dose schedule significantly reduced any cell line. Our data support the relevance of timing of prednisone dose in altering the inflammatory milieu and spirometric decline associated with nocturnal worsening of asthma. PMID- 1456571 TI - Bronchial exudation of bulk plasma at allergen challenge in allergic asthma. AB - This study examined plasma exudation into the bronchial lumen after allergen challenge. A novel low-trauma technique was developed to challenge and lavage a medium-sized lingular or middle lobe bronchus. Eleven subjects with challenge assessed pollen-sensitive asthma were allocated to fiberbronchoscopy in the supine position. In the control bronchus 0.5 ml diluent was instilled. The bronchus was occluded proximally 3 min later by inflation of a balloon, and lavage was carried out twice with 25 ml saline. Incremental doses of allergen solution (0.5 ml) were then instilled in the contralateral lung. The challenge continued until a clearly visible bronchial reaction occurred and was immediately followed by the same lavage as on the control side. The lavage liquids were analyzed for the presence of plasma exudation and mast cell activation indices. On the allergen-challenged side, tryptase, reflecting mast cell activation, was increased by 150% (p < 0.01) compared with the control side. Fibrinogen (mol wt 340,000), reflecting large protein exudation, was increased by 840% (p < 0.05), and N-alpha-tosyl-L-arginine-methyl esterase activity, reflecting both large protein exudation and mast cell activation, increased by 480% (p < 0.01). The level of albumin (mol wt 69,000), the major luminal protein under baseline conditions, increased but not significantly. We conclude that activation of mast cells and luminal entry of little sieved plasma exudates occur early after endobronchial allergen provocation in human subjects with allergic asthma. PMID- 1456572 TI - Inhibition by L-NG-nitro-L-arginine of nonadrenergic-noncholinergic-mediated relaxations of human isolated central and peripheral airway. AB - Human isolated central (5 to 12 mm) and peripheral (< 2 mm) bronchi were contracted with 3 microM histamine. Relaxations were then evoked by electrical field stimulation (EFS) (1 to 32 Hz, 1 ms, 12 V for 15 s in the presence of indomethacin, atropine, and propranolol). The magnitude, time-course, and frequency-response relationship of these nonadrenergic, noncholinergic (NANC) relaxations were similar in the central and the peripheral airways. NG-Nitro-L arginine (L-NOARG) (10 microM) inhibited the tetrodotoxin-sensitive NANC relaxations in both central and peripheral bronchi, whereas the stereoisomer D NOARG was without effect. This inhibition was reversed by L-arginine (1 mM) but not be D-arginine (1 mM). The nitric oxide donor compound, 3 morpholinosydnonimine (SIN-1), was equipotent at relaxing the central and peripheral airways. Vasoactive intestinal peptide (VIP), although it relaxed central airways, was virtually ineffective in relaxing the peripheral airways. In addition, the peptidase, alpha-chymotrypsin, at a concentration that blocked relaxations to VIP, was without effect on NANC relaxations in the central bronchi. The results support the following hypotheses: (1) both central and peripheral airways receive nonadrenergic relaxant innervation; (2) the relaxant response to electrical stimulation of this system is dependent on a pathway involving L-arginine; and (3) the relaxant response does not appear to involve VIP, but it may involve the production of nitric oxide. PMID- 1456573 TI - Excitatory role of axon reflex in bradykinin-induced contraction of guinea pig tracheal smooth muscle. AB - To elucidate the role of the axon reflex in the airways, we studied the effects of atropine (10(-6) M) and tetrodotoxin (10(-7) M) on the bradykinin-induced contraction of guinea pig tracheal smooth muscle, with or without pretreatment of the animals with capsaicin. The concentration-response curves to bradykinin (10( 9) to 10(-5) M) were measured in the presence of both indomethacin and propranolol. In the guinea pigs not given capsaicin pretreatment, baseline tension values did not differ before versus after the application of atropine or tetrodotoxin. Tetrodotoxin reduced the bradykinin-induced contraction significantly, but atropine did not change the contraction induced by bradykinin. These observations indicate that bradykinin-induced contraction is potentiated by a neurally mediated action, but that is not mediated by acetylcholine released from the efferent vagal nerve terminals. The contractile response to bradykinin was significantly reduced in the animals treated with capsaicin as compared with those administered vehicle only. Furthermore, in the animals treated with capsaicin, tetrodotoxin did not affect the response to bradykinin. These observations indicate that bradykinin-induced airway smooth muscle contraction is mediated in part by tachykinins released from C-fiber endings, presumably via an axon reflex. PMID- 1456574 TI - Guinea pig model of immunologic asthma induced by inhalation of trimellitic anhydride. AB - We established a model of asthma induced by trimellitic anhydride (TMA) in guinea pigs and assessed the role of sensitization in the development of their bronchial hyperresponsiveness, and relationship between bronchial responsiveness and bronchial inflammation. Fourteen guinea pigs (sensitized group) were administered 1 mg/0.5 ml of trimellity 36-bovine serum albumin intramuscularly and 0.5 ml of complete Freund adjuvant on Day 1 as the priming dose. Booster doses were repeated on Day 15. By Day 28, all of the sensitized animals showed a high passive hemagglutination titer against trimellityl 14-ovalbumin. On Day 29, they were challenged by an inhalation of TMA (150 mg/m3) for 30 min, and respiratory resistance (Rrs) was monitored by the oscillation method. In all sensitized animals, Rrs increased immediately upon challenge and returned to baseline within 6 h. The bronchial reactivity to acetylcholine (Ach), measured 6 h after TMA challenge in the sensitized animals, increased significantly (p < 0.01) compared with that measured 24 h before challenge; that measured 24 h later was not different from that before challenge. There was also a significant difference (p < 0.01) in the number of eosinophils in the lamina propria and the epithelium 6 and 24 h after the challenge inhalation in the sensitized group. The increased airway responsiveness to Ach in the sensitized animals was correlated with an increase in the number of eosinophils in the lamina propria and the epithelium. These observations suggest that humoral antibody and eosinophils are involved in the pathogenesis of TMA-induced asthma. PMID- 1456575 TI - Metered-dose inhaler adherence in a clinical trial. AB - We studied patterns of inhaler usage in a sample of participants from two centers in the Lung Health Study clinical trial. The inhaler, containing either ipratropium bromide or a placebo, was prescribed to be taken as two inhalations three times daily. For 4 months we recorded adherence by both self-report (n = 95) and canister weight change (n = 70). We compared these results with data obtained from a microprocessor monitoring device, the Nebulizer Chronolog (NC), which records the date and time of each inhaler actuation. Seventy-three percent of the participants reported using the inhaler an average of three times daily; however, NC data showed that only 15% of the participants actually used the inhaler an average of 2.5 or more times per day. Canister weight overestimated adherence because only 62% of the NC sets contained the prescribed two actuations. Fourteen percent showed a pattern of actuation of their inhalers more than 100 times in a 3-h interval. We interpret this usage pattern to reflect deliberate emptying of inhalers to appear to be in good compliance with the prescribed program. We conclude that self-report and weighing of inhaler canisters overestimate adherence to the prescribed regimens. Furthermore, a substantial number of monitored inhaler users appear to deliberately dump their medication prior to follow-up visits. PMID- 1456576 TI - Lymphocytic alveolitis and pleural calcifications in nonoccupational asbestos exposure. Protection against neoplasia? AB - Inhabitants of the Metsovo area in Northwest Greece (population, 4,000) have been exposed to asbestos through the use of whitewash containing tremolite. This has resulted in endemic pleural calcifications (PCs) and increased incidence of malignant pleural mesothelioma (MPM). In order to evaluate the lung response to the fiber, bronchoalveolar lavage (BAL) was performed in 25 Metsovites; 14 with PCs, three with PCs and neoplasia, five without PCs, and three without PCs but with established neoplasia. There were no differences between the four groups with regard to age or exposure. Twelve Metsovites had lymphocytic alveolitis (BAL lymphocytes > 15%). Eleven belonged to the group with PCs and one belonged to the group without PCs. None of those with neoplasia had alveolitis. The lymphocytes were mainly helper T-cells, and activation markers were more frequent among those with PCs. We have previously reported on the relative absence of PCs in Metsovites with malignant pleural mesothelioma. This observation and the results of the present study suggest that lymphocytic alveolitis correlates with pleural calcifications, whereas both are rarely present in patients with neoplasia. PMID- 1456577 TI - Immunocytochemistry and ELISA quantitation of mucin for diagnosis of malignant pleural effusions. AB - One hundred and thirty-five pleural effusions with definite etiology were analyzed by mucin-specific monoclonal antibody (17Q2)-derived enzyme-linked immunosorbent assay (ELISA). Twenty-four effusions were transudate, 45 were nonmalignant exudate, and 66 were malignant. Among the 66 malignant effusions, 52 were adenocarcinoma, and 14 were malignancies other than adenocarcinoma. Purified mucous glycoproteins from sputa of normal subjects were used as ELISA standard. Our results showed that the mean mucin concentration in malignant pleural effusions were significantly higher than that of benign exudates (8.41 +/- 13.48 ng/ml versus 1.09 +/- 0.82 ng/ml, p < 0.01). Mucin concentration in malignant pleural effusions caused by adenocarcinoma was also significantly higher than in non-adenocarcinoma effusions (9.96 +/- 14.81 ng/ml versus 2.66 +/- 1.74 ng/ml, p < 0.01). With the use of mean +/- 2 SD of mucin concentration in benign exudates as a cut-off value (2.73 ng/ml), the sensitivity of this assay for diagnosis of malignant effusions was 66.7%, specificity was 97.1%, and accuracy was 82.2%. High levels of mucin concentration were more specifically associated with adenocarcinoma. When the mucin concentration in pleural effusions was greater than 5 ng/ml, 93.1% (27/29) of patients were adenocarcinoma. If the mucin concentration was greater than 10 ng/ml, 100% (14/14) of patients were adenocarcinoma. Immunofluorescent staining by mucin-specific monoclonal antibody 17Q2 were also carried out in diastase-treated cell preparations obtained from 22 patients with malignant pleural effusions and 16 benign exudates. Nine of 14 adenocarcinomas (64.2%) were reactive with monoclonal antibody 17Q2, while none of the benign exudates, squamous cell carcinomas, and mesotheliomas were stained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456578 TI - Evaluation of cor pulmonale on a modified short-axis section of the heart by magnetic resonance imaging. AB - Magnetic resonance imaging (MRI) of a modified short-axis section of the heart, in 36 patients with chronic pulmonary diseases, consisting of 19 patients with pulmonary hypertension (PH group; mean pulmonary arterial pressure > or = 20 mm Hg) and 17 patients without pulmonary hypertension (non-PH group) was evaluated to study the configuration of the right ventricle. Parameters of right ventricular hypertrophy, including right ventricular wall thickness (RVWT) and the ratio of RVWT to left ventricular posterior wall thickness (RVWT/LVPWT), with this method were significantly larger in the PH group than in the non-PH group (p < 0.01). RVWT and RVWT/LVPWT correlated well with mean pulmonary arterial pressure (r = 0.90, p < 0.001 and r = 0.89, p < 0.001), total pulmonary resistance (TPR; r = 0.88, p < 0.001 and r = 0.85, p < 0.001), and pulmonary arteriolar resistance (PAR; r = 0.83, p < 0.001 and r = 0.81, p < 0.001). This method of setting a patient in a supine position and slicing with single-oblique sections may seem overly simple compared with Dinsmore's double-oblique short axis section of the heart, but it is more convenient in practice. These results suggest that a modified short-axis section of the heart by MRI provides valid clinical configurational information concerning the right ventricle on which to base a noninvasive diagnosis of cor pulmonale. PMID- 1456579 TI - CD3+ and CD4+ cells adoptively transfer experimental hypersensitivity pneumonitis. AB - To characterize the cells responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis (EHP), we depleted Micropolyspora faeni (M. faeni)-sensitized C3H/HeJ spleen cell (SC) cultures of CD3+, CD4+, or CD8+ cells before administration to recipients. We determined the length of time sensitization persists, the ability of cultured lung-associated lymph node (LALN) cells to transfer EHP, and the ability of cultured SC from animals subjected to two, four, or eight weekly intratracheal challenges of M. faeni to transfer EHP. The extent of pulmonary inflammatory response after challenge with intratracheal M. faeni was used to determine adoptive transfer. Depletion reduced the proportion of CD3+ cells from 21 to 1%, CD4+ cells from 15 to 3%, and CD8+ cells from 7 to 1% in the cultured SC population. The proportion of B cells exhibited reciprocal changes. Cultured SC could transfer EHP. Depletion of CD3+ and CD4+, but not CD8+ cells, ablated or diminished the capacity to transfer EHP. Sensitized cells persisted in recipients for at least 8 wk. Cultured LALN cells could transfer EHP. Recipients of cultured SC from 4- and 8-wk donors exhibited less extensive pulmonary abnormalities than recipients of cultured SC from 2-wk donors. The proportion of CD3+, CD4+, CD8+, B cells, and macrophages was the same in cultured cells from 2-, 4-, and 8-wk donors. We conclude that the active cells in SC cultures are CD3+, CD4+, and CD8- T cells, and there are differences in the ability of cultured cells to adoptively transfer EHP that are dependent on the nature of the donor but not on the phenotype of the cell population. PMID- 1456580 TI - In vivo detection of a novel macrophage-derived protein involved in the regulation of mucus-like glycoconjugate secretion. AB - We previously described a novel 68,000 D macrophage-derived protein (MMS-68) that can stimulate mucus-like glycoconjugate (MLGC) secretion from cultured human airways, respiratory epithelial cells, and the ishikawa adenocarcinoma cell line. To better characterize this mucus secretagogue, we generated monoclonal antibodies against MMS-68 by injecting crushed SDS-PAGE gel slices containing this protein into Balb-C mice followed by fusion with SP2/0, a nonsecreting mouse myeloma cell line. A panel of monoclonal antibodies was produced that identified the 68,000 D MMS by immunoblot analysis and immunoprecipitation. The monoclonal antibodies detected MMS-68 in normal peripheral blood monocytes and pulmonary macrophages by cytofluorographic analysis and in human airways as determined by immunohistochemistry. Utilizing the monoclonal antibodies, an antigen-capture ELISA assay was developed. Statistically significant elevations in levels of MMS 68 were detected in bronchoalveolar lavage fluid (BALF) of chronic bronchitic subjects and cigarette smokers and in monocyte culture supernatants from steroid dependent asthmatic patients compared to normal control subjects. The 68,000 D MMS is a potent secretagogue and may play an important role in the regulation of mucus secretion, especially in chronic bronchitis and steroid-dependent asthma. PMID- 1456581 TI - Bacterial tracheitis with upper airway obstruction in a patient with the acquired immunodeficiency syndrome. AB - Bacterial tracheitis after an upper viral respiratory infection is a well recognized entity in the pediatric literature. Bacterial tracheitis has only recently been reported in adults, and it is a potentially life-threatening illness. We report a case of bacterial tracheitis in a patient with AIDS. PMID- 1456582 TI - Hard metal pneumoconiosis and the association of tumor necrosis factor-alpha. AB - Hard metal pneumoconiosis is a recently recognized occupational lung disease associated with the exposure to cobalt fumes in the workplace. Chronic exposure in susceptible individuals results in interstitial lung disease histopathologically manifested as interstitial fibrosis with an associated mononuclear cell infiltrate and the presence of "cannibalistic" multinucleated giant cells in the alveolar airspaces. The majority of patients present with symptoms of chronic cough and dyspnea. Interestingly, in addition, patients uniformly report significant weight loss out of proportion to their degree of respiratory impairment. In this case report we demonstrate the association of tumor necrosis factor-alpha (TNF) and hard metal (cobalt) pneumoconiosis and suggest that TNF may have a potential role in the etiology of the constitutional symptoms and the pathogenesis of interstitial lung disease. PMID- 1456583 TI - Pulmonary and intestinal microsporidiosis in a patient with the acquired immunodeficiency syndrome. AB - The microsporidian protozoan organism Enterocytozoon bieneusi has been found in enterocytes of the small intestine in patients infected with human immunodeficiency virus, and it has been recognized as an important cause of chronic diarrhea in this patient group. We report the first case of a 41-yr-old man with acquired immunodeficiency syndrome in whom microsporidia were detected in bronchoalveolar lavage fluid, transbronchial lung biopsies, stool specimens, and ileal biopsies. He experienced chronic diarrhea, wasting syndrome, chronic cough, and dyspnea. His chest roentgenogram showed a small left posterobasal infiltrate and a small left pleural effusion. The histologic pattern of microsporidia in his bronchial and ileal tissue and the cellular inflammatory reaction with intraepithelial infiltration by lymphocytes were identical to findings described in duodenal and jejunal Enterocytozoon bieneusi microsporidiosis. An association between the presence of microsporidia in the lung and the pulmonary symptoms has yet to be determined. It is not known whether pulmonary microsporidiosis was acquired by the aerosol route, by aspiration, or by hematogenous dissemination from the intestine. PMID- 1456584 TI - Bronchial hyperresponsiveness and level of exposure in occupational asthma due to western red cedar (Thuja plicata). Serial observations before and after development of symptoms. AB - Four workers from a cedar sawmill who developed red cedar asthma are described. They had serial measurements of lung function and nonspecific bronchial hyperresponsiveness (NSBH) several years before and after the development of chest symptoms. Measurements of dust concentration and specific IgE antibodies to plicatic acid-human serum albumin (PA-HSA) conjugate were also carried out before the onset of disease. NSBH developed in parallel with the development of asthma and was not present in any of the workers beforehand, indicating that it is not a predisposing host factor. Nasal symptoms preceded chest symptoms in three workers, suggesting that this may be an early marker of the disease. Although dust concentrations for jobs located both inside and outside the sawmill were low, jobs associated with somewhat higher exposures were associated with the initiation of asthma symptoms. PMID- 1456585 TI - Hypercapnic ventilatory response in recipients of double-lung transplants. AB - Ten survivors of double lung transplantation using a tracheal anastomosis underwent assessment of their ventilatory responses to hypercapnia (HCVR) at least 3 months postsurgery. At the time of HCVR testing, pulmonary functions were normal in four and abnormal in six patients who demonstrated degrees of obstruction, restriction, or mixed defects. Arterial blood gas measurements were normal. Postoperatively, hypercapnic responses were low or low normal. Mean changes in tidal volume and mean change in respiratory frequency in response to hypercapnia postoperatively were not different in patients with normocapnic versus hypercapnic preoperative blood gases. Neither postoperative resting PCO2 nor muscle strength (as measured by MIP) were predictive of the degree or character of the patients' ventilatory responses to hypercapnia. The factors resulting in the observed blunting of the hypercapnic response in this denervated population require further clarification; however, comparison of data between this patient population and recipients of heart-lung transplantation reported elsewhere suggests that alterations in pulmonary function correlate with the observed depression in HCVR. PMID- 1456586 TI - Bicarbonate concentration in rhesus monkey and guinea pig fetal lung liquid. AB - Fetal lung liquid secretion is essential for the normal growth of the lung in utero. Previous studies of fetal lung liquid secretion, mostly performed in lambs, have demonstrated that it has high Cl and very low HCO3- concentrations relative to plasma values. Because it is unknown whether primates have a similar electrolyte profile in their lung liquid, we sampled the lung liquid from rhesus monkeys (Macaca mulatta) at 127 to 128 days gestation (0.8 gestation). Although we found that lung liquid Cl concentration was higher than plasma values (p < 0.05), the HCO3- concentration was the same as in the plasma. This indicates that nonhuman primates, relative to lambs, have different cellular mechanisms for regulating fetal lung liquid HCO3- concentrations. PMID- 1456587 TI - Emphysema: the first two centuries--and beyond. A historical overview, with suggestions for future research: Part 2. PMID- 1456588 TI - Control of tuberculosis in the United States. American Thoracic Society. AB - TB continues to be a major public health problem in many areas of the United States. Elimination of this disease will require coordinated efforts of public health agencies, voluntary health associations, health-care providers, and community groups. TB controls is comprised of a variety of activities. Identification and treatment of patients with clinically active disease should be the highest priority for all TB control programs. Identification and preventive treatment of infected contacts and persons with tuberculous infection at greatest risk for developing disease (eg, HIV-infected, young children) should also receive high priority. Attention should then be given to identifying other high risk groups and administering preventive therapy to those infected. While TB control occurs in many different settings, the health department TB control program plays a pivotal role in providing clinical services, and performing contact investigations, tuberculin-testing and prevention activities, surveillance, and evaluation of the community's overall progress in TB elimination. Health departments should receive strong and continuing support from medical care providers, voluntary health organizations, and community groups if TB elimination is to be achieved. PMID- 1456589 TI - Proportional assist and negative-impedance ventilation. PMID- 1456590 TI - Isoniazid-associated hepatitis deaths: a review of available information. PMID- 1456591 TI - Isoniazid-associated hepatitis deaths: a review of available information. PMID- 1456592 TI - Effectors of hypercarbia during experimental pneumoperitoneum. AB - Hypercarbia occurs during laparoscopy with carbon dioxide (CO2) insufflation. This may be due to increased ventilatory dead space after expansion of the peritoneal cavity with impairment of diaphragmatic excursion, or to increased absorption of CO2 from the peritoneum. To separate these effects, the authors examined the consequences of different insufflating gases and of diminished tissue perfusion on hypercarbia and dead space during pneumoperitoneum. Helium was chosen as an alternate insufflating gas because it is both inert and minimally absorbed. Eight swine (18 to 20 kg) were anesthetized, paralyzed, and mechanically ventilated at constant minute volume. Pneumoperitoneum with helium was maintained at 15 mm Hg for 45 minutes. After desufflation and stabilization for 1 hour, pneumoperitoneum was repeated with CO2. The sequence was again repeated after hemorrhagic shock to constant mean arterial pressure of 50 mm Hg. Data was analyzed by analysis of variance; significance levels are P < 0.01 unless otherwise listed. Arterial PCO2 increased significantly with CO2 insufflation within 15 minutes in normotensive animals and within 30 minutes during hypotension. Arterial pH decrease with CO2 pneumoperitoneum was significant in both groups at 30 minutes. Mixed venous PCO2 also increased with CO2 pneumoperitoneum within 30 minutes. Hypotension did not alter these changes. No significant changes were seen with helium pneumoperitoneum. Neither helium nor CO2 pneumoperitoneum significantly altered dead space. The authors make the following conclusions: 1) Absorption of CO2 from the abdomen during CO2 pneumoperitoneum produces respiratory acidosis, which is not seen with helium insufflation; 2) Pneumoperitoneum does not significantly increase dead space with either gas; 3) Transperitoneal absorption of CO2 is only partly related to perfusion because significant hypercarbia occurs during hemorrhagic shock. PMID- 1456593 TI - A new method for microvascular anastomosis: report of experimental and clinical research. AB - Principles of microvascular anastomotic surgery are uncertain in contrast to the standardized suture methods for the repair of large arteries. Complications of early thromboses or late stricture at the microvascular anastomotic line can be related to the inherent biologic response of these delicate tissues to penetrating needle and suture. A new method for microvascular reconstruction based on the principle of flanged, nonpenetrated, intimal approximation by an arcuate-legged clip has proven biologically and technically superior to the penetrating microsuture. These conclusions are based on extensive testing in multiple surgical laboratories of the following parameters: long- and short-term patency, morphology of wound repair, and burst and tensile strength. Details of the new surgical system and experimental studies are described. PMID- 1456594 TI - Glucose intolerance in critically ill surgical patients: relationship to total parenteral nutrition and severity of illness. AB - The authors evaluated the relative influence of severity of illness and total parenteral nutrition (TPN) on glucose intolerance in critically ill surgical patients. Records of TPN administration, serum glucose measurements, and the simplified acute physiology score (SAPS) were extracted from the surgical intensive care unit (SICU) and hospital clinical information systems (CIS) for all patients admitted to the SICU from October 1, 1989 through March 31, 1990. Critical hyperglycemia was defined as glucose > 400 mg/dL and critical hypoglycemia as < 40 mg/dL. During the study period, 1,129 patients received 3,054 days of care, including 88 patients who received 705 days of TPN. Of 4,985 glucose determinations performed during the study period, 48 (0.96%) were critically abnormal. Critical hyperglycemia occurred in 1.7 per cent of blood samples from TPN patients, compared to 0.7 per cent in non-TPN patients (P < 0.005). However, the mean admission and daily and maximum severity of illness scores were significantly higher in TPN patients compared to non-TPN patients (all P < 0.0005). Mean glucose levels rose with increasing SAPS in both TPN and non-TPN patients. When stratified by severity of illness, TPN patients did not have significantly higher glucose levels than non-TPN patients except for the SAPS = 15 category. The authors conclude that the glucose intolerance noted in critically ill TPN patients reflects their underlying severity of illness rather than TPN administration per se. PMID- 1456595 TI - Subcapsular hematoma as a predictor of delayed splenic rupture. AB - Over the past 46 months at a level I trauma center, 966 computed tomography (CT) scans were performed for blunt abdominal trauma. Eighty-three (8.6%) demonstrated splenic injury, and 31 (3.2%) of these showed a subcapsular hematoma with or without associated parenchymal damage. Of the 31 patients, 23 were managed conservatively, based initially upon surgeons' preference (14 patients) and after March 1990 to conform to the authors' splenic trauma protocol (nine patients). The eight patients operated upon were hemodynamically stable and all underwent splenectomy. Subcapsular hematoma, as diagnosed by preoperative CT scan, was confirmed in each of the eight celiotomies. Parenchymal involvement, which had also been identified in these eight patients by CT, was evident at operation in all, and hilar involvement occurred in three. None of the 23 observed patients developed delayed splenic rupture. All were discharged home with outpatient follow-up in surgical clinic to at least 1 month without further complication. The authors came to the following conclusions: 1) Subcapsular hematoma is neither a predictor for delayed splenic rupture, nor by itself an indication for operative management of the injured spleen in the hemodynamically stable patient; 2) Degree of parenchymal injury based on CT morphology, specifically hilar involvement, signifies the need for laparotomy with splenectomy; 3) Splenorrhaphy has a reduced role in splenic trauma because most injuries now operated upon are severe. PMID- 1456596 TI - A critical analysis of blood transfusion requirements in children with blunt abdominal trauma. AB - Over the past 2 years, 178 children with blunt abdominal trauma were admitted for observation. Fifty-five patients (31.5%) had intra-abdominal injury confirmed by computerized tomography (CT) scan, laparotomy, or postmortem examination. Forty four children (80%) were managed with observation only; nine had other operations. Eleven patients (20%) required an operation for their intra-abdominal injuries. Thirteen patients died, ten from head or spinal injuries and three from intra-abdominal injuries (5.5%). Of 35 children with intra-abdominal injuries observed without any type of operation, 27 (77%) were not transfused (mean Pediatric Trauma Score [PTS] 8, Injury Severity Score [ISS] 19.3, average low hemoglobin [ALH] 10.1). The other eight were transfused an average of 49 cc/kg (mean PTS 4.5, ISS 26.5 ALH 6.1). Twenty children had operations. Eleven 11 (20%) of these were laparotomies; nine were transfused an average of 200.6 cc/kg (mean PTS 6, ISS 33, ALH 9). Nine had neurosurgical/orthopedic procedures (mean PTS 6.2, ISS 27.7), with six transfusions averaging 84.9 cc/kg (ALH 8.9). There were no significant complications. Blood transfusion was necessary only for 33 per cent of the observed cases, usually with multiple injuries. Blood should be transfused only to maintain hemodynamic stability (normal vital signs and tissue perfusion). Hemoglobin levels as low as 7 gm% do not mandate transfusion in children who are hemodynamically stable. PMID- 1456597 TI - Continuous intra-arterial oxygen monitoring: accuracy and reliability in the surgical intensive care unit. AB - The accuracy and reliability of an invasive intra-arterial oxygen sensor catheter was evaluated in 20 critically ill surgical intensive care unit (SICU) patients. All patients required continuous arterial blood pressure monitoring, at least 72 hours of ventilator support, and intermittent arterial blood gas sampling for clinical management. The intra-arterial sensor provided continuous PO2 (PsO2) values on a bedside electronic monitor. PsO2 values were sampled every 60 seconds and automatically stored on a bedside personal computer. Arterial blood gas (ABG) PaO2 values were collected and matched by collection time with corresponding PsO2 values. During 1,238 hours of continuous intra-arterial monitoring, 74,280 PsO2 values and 246 ABG PaO2 values were collected. Of the 246 PaO2 results, 175 (71.3%) had a matching PsO2. Regression of matched PsO2 and PaO2 values yielded a correlation coefficient of 0.58 and standard error of the estimate (SEE) of 33.1 (P < 0.0005). Even though matched PsO2 and PaO2 measurements demonstrated a linear relationship, only 34 per cent of the variation in PsO2 could be attributed to changes in PaO2. Technical sensor or instrument problems affected PsO2 monitoring in 17 of 20 patients and 28 of the 33 sensors tested. The authors conclude that continuous intra-arterial monitoring of PsO2 is a novel idea, but technical issues limit its use in acutely ill, conscious SICU patients. PMID- 1456598 TI - Occult traumatic pneumothorax: immediate tube thoracostomy versus expectant management. AB - Occult pneumothorax is pneumothorax identified by computed tomography but not seen on conventional chest radiographs. Twenty-seven occult traumatic pneumothoraces in 26 patients were identified retrospectively at the authors' level I trauma center. Of these, 24 patients survived to discharge or transfer; 2 died of brain injury. Eleven patients were treated immediately with tube thoracostomy (TT) and 13 were observed with interval chest radiography. The authors' data support the conclusion that it is safe to withhold immediate TT in patients who are hemodynamically stable. Close clinical observation and interval chest radiography can identify those patients who require subsequent TT. Prospective study of larger numbers of patients is needed to confirm the safety and cost efficacy of this approach. PMID- 1456599 TI - Incidental preclinical hyperparathyroidism identified during thyroid operations. AB - The entity of preclinical hyperparathyroidism has never been clearly investigated. The authors believe that the incidence of pathologic abnormalities of the parathyroid glands before the development of any symptoms or hypercalcemia (serum calcium > 12.0 mg/dl) is more frequent than has been reported. Over a 14 year period, parathyroid glands were examined during thyroid operations in over 800 patients. Serum calcium and phosphorous levels were measured in all patients preoperatively. Thirty-six patients had additional parathyroid operations for a preclinical form of hyperparathyroidism, defined by abnormal appearing parathyroid glands at the time of thyroid surgery. None of the 36 patients had symptoms of hyperparathyroidism preoperatively. Nine patients had borderline hypercalcemia (serum calcium 10.6 to 12.0 mg/dl), and the remainder were considered normocalcemic. The average age was 53 (range 21 to 75) with a male to female ratio of 1:3. Nine of the 36 patients had thyroid cancer. There were eight patients with parathyroid adenoma and 28 patients with parathyroid hyperplasia. Of 13 patients who had a history of neck irradiation, five had parathyroid adenoma and eight had parathyroid hyperplasia. Only two patients with parathyroid hyperplasia remain on calcium medication. Since preoperative normocalcemia does not preclude the presence of parathyroid pathology, the authors urge careful identification and examination of the parathyroid glands during thyroid operations. It adds little time to the procedure. Excision of parathyroid disease along with the thyroid gland can be performed safely and prevents the need for further operation with its associated morbidity. PMID- 1456600 TI - Seroma prevention after modified radical mastectomy. AB - The most common mastectomy-associated complication is seroma formation. Seromas can be associated with other more serious complications such as skin flap necrosis, delayed wound healing, infection, and lymphedema. The flap tacking procedure that closes the axillary fossa dead space and tacks the mastectomy flaps to the chest wall has been suggested as one potential technique to reduce the incidence of postmastectomy seromas. This institution-wide study of modified radical mastectomies demonstrated a significant decrease (P < 0.0381) in the incidence of seroma when flap tacking was performed. Women who developed a seroma, compared to those who did not, averaged nearly twice as any office visits in the first 2 months after the operation. Distribution of office visits between the seroma patients and nonseroma patients was significant (P < 0.0001). When practiced by several surgeons, the flap tacking procedure 1) reduces postmastectomy seromas and 2) reduces the amount of postoperative patient office visits and care. PMID- 1456601 TI - Simple surgical treatment of nonparasitic hepatic cysts. AB - Benign nonparasitic liver cysts are uncommon lesions. Incidental diagnosis is increasing with the advent of routine abdominal computed tomography and ultrasound scanning. Cysts that attain massive proportions often become symptomatic and require therapeutic intervention. Surgical resection and Roux-en Y cystojejunostomy drainage have been the treatments of choice, but simpler unroofing techniques without drainage have recently been employed with success. Three patients with symptomatic, large, nonparasitic cysts were surgically treated in such a fashion without complication and form the basis of this report. The technique of wide unroofing involves excision of the nonhepatic cyst wall with oversewing of communicating biliary radicals. No recurrences have been detected in follow-up screening. Wide unroofing is a simple and yet reliable surgical option for the treatment of symptomatic hepatic cysts. PMID- 1456602 TI - Immunohistochemical determination of the estrogen receptor content of gastrointestinal adenocarcinomas. AB - Recently there have been several reports documenting the presence of estrogen receptors (ERs) in human gastrointestinal (GI) malignancies, raising the possibility that these cancers may be hormonally manipulated. To test this hypothesis, 68 frozen GI tissue specimens were examined for the presence of ERs within the cell nuclei by immunohistochemical staining. There were 51 cancers (25 gastric, 26 colon) and 17 normal tissue specimens (six gastric, 11 colon). Tissue sections 4 to 6 microns thick were incubated with monoclonal antibody H222SP psi, then stained by the peroxidase-antiperoxidase technique for visualization of the ER. The staining was semiquantitatively graded from 0 to 3+ depending on both the intensity of staining and the percentage of cell nuclei stained. A breast cancer specimen known to be strongly positive for the ER was used as a positive control. The 30 male and 21 female cancer patients had a median age of 59 years. All tumors were adenocarcinomas. Eight per cent of the gastric cancers were poorly differentiated, while 94 per cent of the colon cancers were moderately well to well differentiated. Using weak staining of at least 20 per cent of the cell nuclei as the minimum requirement for an ER positive tumor (1+, 0/51 tumors and 0/17) normal specimens were positive for ER. Only three out of 25 (12%) gastric tumors, and two out of 26 (8%) colon tumors demonstrated any staining; each exhibited weak staining of only five to ten per cent of the tumor nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456603 TI - Detection of acute appendicitis by technetium 99 HMPAO scanning. AB - The diagnosis of acute appendicitis can be difficult. Barium enemas, computed tomography (CT) scans, ultrasound examinations and Indium scans are used to aid in making the diagnosis with varying degrees of success. This blinded, prospective study reports the use of a Technetium 99-m Hexamethylpropyleneamineoxide (HMPAO) labelled white blood cell scan in 30 patients with suspected appendicitis. Autologous white blood counts from 25 cc of whole blood labelled with Tc-99 HMPAO were reinjected into patients. Abdominal imaging was performed at a half hour postinjection and repeated at 2 to 4 hours postinjection. A positive study showed an increased isotope uptake in the right lower quadrant. Nineteen patients had histologically proven appendicitis. Three of these patients were excluded because they were operated on before scan completion. Thirteen of the remaining 16 patients with appendicitis had positive studies (false negative rate = 19%). All patients without appendicitis had either negative scans or scans that detected other intra-abdominal diseases, such as diverticulitis, tubo-ovarian abscess, or small bowel infarction (false positive rate = 0%). Overall, this Tc-99 HMPAO study had a sensitivity of 81 per cent, a specificity of 100 per cent and an overall accuracy of 89 per cent. The 4-hour Tc 99 HMPAO WBC scan is a useful, noninvasive test for confirming the clinical diagnosis of acute appendicitis, but it may prove more valuable as a diagnostic study to rule out appendicitis in patients that have abdominal pain of unclear etiology. PMID- 1456604 TI - Iatrogenic bile duct injuries. The real incidence and contributing factors- implications for laparoscopic cholecystectomy. AB - Laparoscopic cholecystectomy has achieved wide acceptance as the preferred treatment for symptomatic gallbladder disease. Yet there are alarming reports of iatrogenic bile duct injuries. To establish a comparison standard, the incidence of iatrogenic bile duct injury during conventional cholecystectomy has to be known. A single institutional retrospective review of 1,617 consecutive open cholecystectomies between 1980 and 1989 was performed. Eight patients (0.49%) sustained iatrogenic bile duct injury in this study. Inflammation, anatomic variation, or both were contributing factors in all injuries. Operative cholangiography identified the injury at the initial operation in three patients. Treatment consisted of either primary ductal repair, ductal repair over a stent, or ductal-enteric anastomosis. There were no late complications after surgery (follow-up 26 to 97 months; mean 50.9 months). The implications for laparoscopic cholecystectomy are apparent. Iatrogenic bile duct injuries are associated with acute inflammation and/or variant ductal anatomy; routine operative cholangiography assumes increased importance; and immediate repair of the injury minimizes long-term complications. PMID- 1456605 TI - Gastroduodenal intussusception secondary to a gastric lipoma: a case report and review of the literature. AB - Gastroduodenal intussusception is an extremely uncommon condition usually caused by the prolapse of a benign gastric tumor into the duodenum with subsequent invagination of a portion of the stomach wall. A rare case of this condition associated with a gastric lipoma is presented. Clinical manifestations may mimic many other disease entities and are nonspecific. Diagnosis, however, can often be made preoperatively with noninvasive tests, which are usually associated with more specific signs. Treatment involves reduction of the intussusception and surgical excision of the lead point, either endoscopically or through a formal laparotomy. PMID- 1456606 TI - Herpes simplex virus: a possible etiologic agent in some gastroduodenal ulcer disease. AB - There is increasing evidence that the herpes simplex virus may account for some gastric ulcer disease. To examine this possibility, 62 tissue biopsies from 21 patients were obtained during esophagogastroduodenoscopy for gastroduodenal ulcer disease and from one operative specimen during the procedure for perforation of a gastric ulcer. The samples were collected from the base and rim of the ulcer, as well as from apparently healthy tissue adjacent to the lesion. When the DNA was extracted from these tissues and hybridized to a herpes simplex virus-specific DNA probe, positive results were obtained with 9.5 per cent (2 out of 21) of the patients with benign ulcers. Positive signals were obtained only with ulcer associated tissues and never with healthy tissue. Hybridization also occurred with DNA from one ulcerative carcinoma in the study. These data suggest that a subset of ulcer disease may be caused by herpes simplex virus or that this virus may be secondarily associating with these lesions. PMID- 1456607 TI - Cyst of the falciform ligament of the liver: a rare cause of right upper quadrant pain. AB - Cysts of the falciform ligament are rare. Only a dozen cases have been reported in the English literature, with the first reported case in 1909. The etiology of these cysts is diverse but can be classified into primary and secondary causes. No specific complex exists and their presentations vary among persons. Physical examination may demonstrate a mass in the right upper abdomen. Although rare, they should be considered in the differential diagnosis of right upper quadrant abdominal pain. They are treated through excision. PMID- 1456608 TI - Carcinoma arising in a duplicated colon. AB - One case of adenocarcinoma arising in a duplicated transverse colon is presented. Its unusual feature was the site of the carcinoma origin, which was the true colonic segment and not the duplication. PMID- 1456609 TI - Vesico-diverticular fistula: a rare complication of Meckel's diverticulum. AB - Enterovesical fistulas usually result from diverticulitis, Crohn's disease, or colorectal cancer. A perforated Meckel's diverticulum can also result in an vesico-diverticulum fistula, as noted in three previously reported cases. In all three cases, bladder or bowel disease was associated with the fistula. Herein, the authors describe a previously healthy, 23-year-old man who presented with an enterovesical fistula. Exploratory laparotomy revealed a vesico-diverticular fistula resulting from a perforated Meckel's diverticulum. Pathologic examination revealed that the diverticulum did not contain ectopic gastric or pancreatic tissue and that the perforation was secondary to an enterolith. The patient underwent a diverticulectomy and had an uneventful postoperative course. Unlike any of the three previously reported cases, the authors' patient had no coexisting bowel or bladder disease occurring with his vesico-diverticular fistula. To the authors' knowledge, this is only the third reported case of a vesico-diverticular fistula resulting from a perforated Meckel's diverticulum that did not contain ectopic tissue. It represents the first case where the perforation was secondary to an enterolith. PMID- 1456610 TI - Surgical treatment of the enterogastric reflux syndrome: preoperative and postoperative estimation by 99mTc-HIDA scintigraphy. AB - Twenty-nine patients with enterogastric reflux syndrome after anti-ulcer gastric surgery underwent a revisional Roux-en-Y gastrectomy. The diagnosis of enterogastric reflux syndrome was based on symptomatology and endoscopy in the first eight patients. The latter 21 patients had, in addition, a 99mTc-HIDA scintigraphy for the documentation and measurement of reflux. An enterogastric reflux index > 20 per cent is considered to justify symptoms due to reflux. Three of the first eight patients continued postoperatively to experience the same symptoms as before. These symptoms were eventually attributed to other than enterogastric reflux syndromes. The latter 21 patients were relieved from their preoperative symptoms and classified as Visick I and II (18 patients) and Visick III (3 patients). The authors conclude that enterogastric reflux syndrome must be documented on scintigraphy before the patient is subjected to revisional anti reflux surgery in order for failures due to misdiagnosis to be avoided. PMID- 1456611 TI - Malignant lymphoma of the breast: a review of 13 cases. AB - Thirteen cases of primary malignant lymphoma of the breast are reported from a 15 year retrospective review of records. The ages ranged from 19 to 75 years. One patient had nodular sclerosing Hodgkin's disease and 12 had non-Hodgkin's lymphoma. Eleven patients were treated with local excision, followed by radiotherapy, chemotherapy, or both. One patient had mastectomy and chemotherapy, and one had local excision only. Four patients died 6 months to 7 years after initial diagnosis. One patient was alive and with disease 5 years later. The remainder were alive and free of disease 24 months to 9 years after presentation. Prognosis depended on the clinical stage and histologic grade of the lesion. Five year survival was 72 per cent, which was slightly better than that observed in mammary carcinoma. PMID- 1456612 TI - [Chronic renal insufficiency in childhood]. PMID- 1456613 TI - [Fever and petechial exanthema in children]. AB - In an attempt to determine clinical and analytical predictive parameters of a possible grave disease, we have carried out a retrospective study of 172 children admitted to our hospital with fever and petechiae as initial symptoms. The ages ranged between 1 month and 10 years. Even though we have not found a clinical symptom or analysis sufficiently sensitive as to predict all grave diseases, the general clinical state of the child associated with either a high or low white cell count and an abnormal coagulation study should be alert signals for a serious infectious disease. On the contrary, if the clinical and analytical parameters are within normal limits the risk of a grave disease is low. We emphasize the high incidence of meningococcal disease (26%). PMID- 1456614 TI - [Nutritional status in HIV infection in infancy]. AB - The physiopathology of malnutrition among AIDS, ARC and HIV infected children was reviewed. One-hundred eight-three newborns were studied, 152 of which were born at "La Fe" Maternity Hospital. Of these patients, 29% were LBW and 28% preterm. Transfused and hemophiliac patients were excluded from the study. Anorexia, vomiting, fever, infections of the respiratory and GI tracts and drug therapy were the most frequent factors affecting the nutritional status. Fifty-three newborns were infected with the HIV (29%). The children were classified into three groups (G). Group-I was formed by HIV+children > 18 months of age, G-II, P 2 class by children < 18 months of age and G-III was formed by those children that died of AIDS. The most common symptoms were chronic diarrhea and infections of the respiratory tract. Of the HIV+children > 18 months of age, 65% had a weight < the 10th percentile and 61% were < the 10th percentile for height. Of the children that died of AIDS, 80% were in the lower 10th percentile for both weight and height. Hemoglobin, T4/T8, total proteins, seroalbumin and calcium were also negatively affected. Those most severely affected were the dead patients, followed by P-2 < 18 months and finally the HIV+ > 18 months of age. The differences between G-I and G-II-G-III were statistically significant, p < 0.01. The biochemical quantification of the nutritional status was difficult due to the limited amount of blood available. HIV infected children require nutrition supplementation to maintain an adequate nutritional status. Among these patients, malnutrition is a multifactorial phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456615 TI - [Patterns of breast feeding and study of interfering factors in a primary health care facility]. AB - The present study aims to evaluate the patterns of breast-feeding in a population of children depending on a Primary Attention Team. Its duration and any factors which may interfere with it were also studied. The breast-feeding period of 114 boys and 119 girls is reviewed. We found the following data: 85.2% of the mothers started to breast-feed their children. By the third month, 42.1% of them persisted with exclusive breast-feeding, whereas only 5.6% reached the sixth month. Commercial formulas were introduced as a result of health reasons in only 43.3% of the cases. The time of exclusive breast-feeding was significantly shorter (p < 0.05) in the children who required hospitalization during the breast feeding, in the cases of mothers that smoke, when commercial formula was introduced at the mother's will and in those children who had a smaller weight at their birth and a smaller gestational age. After introduction of commercial formulas we observed a statistically significant increase in weight (p < 0.05). Nevertheless, the standard score of weight at six months of age, compared with that previous to the introduction of lacteal supplements, did not differ significantly. PMID- 1456616 TI - [High frequency ventilation in the newborn. Study of 27 cases]. AB - The clinical histories of 27 neonates ventilated with high frequency respirators (Volumetric Diffusive Respirator VDR-2) have been analyzed in order to evaluate the efficiency of this type of ventilation in neonatal pathology. The average gestational age of these patients was 32 +/- 4 weeks. Most of them (70%) presented respiratory distress due to hyaline membrane disease. Of the remaining cases, three (11%) presented with congenital diaphragmatic hernia, two with pulmonary hypertension, two with meconium aspiration syndrome, one with Group B Streptococal sepsis/shock and one with case diaphragmatic agenesia. Between two and six hours after initiation of high frequency ventilation (HFV), pH, paCO2 and pO2 improved significantly in relationship to former values (p < 0.05- p < 0.001), reaching values in the normal range at 6.5 +/- 14 hours regarding pH, 30 +/- 50 hours regarding paCO2 and 6.5 +/- 10 hours regarding paO2. No hemodynamic modification could be attributed to this procedure. The principal complications were ectopic air (62%) and necrotizing tracheobronchitis (TBN) (25%). Bronchopulmonary dysplasia (BDP) was diagnosed in 20% of the cases, ductus (DAP) in 33% of the cases and intracraneal hemorrhage in 25% of the cases. Mortality was 70%. High frequency ventilation is an alternative procedure to conventional ventilation in this group of neonates. It produces an important number of favorable responses, but has complications that can not be overlooked. PMID- 1456617 TI - [Vertical transmission of HIV infection: descriptive epidemiology, risk factors and survival]. AB - The basic epidemiological characteristics of HIV infection and AIDS among children are described with a particular reference to HIV vertical transmission. The HIV transmission pattern identified in our community is described according to the WHO classification scheme. To describe the epidemic, as well as its temporal evolution, 1.933 cases reported to the population based registry of Catalonia and 287 seropositive children and their mothers are used. We have quantified the importance of intravenous drug usage by the parents in relationship to HIV transmission; 54.7% of the mothers of HIV positive children were intravenous drug users. We predict that during the coming years there will be a continuous increase in AIDS cases as a result of vertical transmission. PMID- 1456618 TI - [Non-Hodgkin's lymphoma in childhood: 19-year experience in a pediatric oncology unit]. AB - Ninety-one patients with Non-Hodgkin's Lymphoma (NHL) were treated in our Pediatric Oncology Unit during a 19 year period. The median age at diagnosis was 5.8 years and there was a higher incidence in males. All patients were classified according to Murphy's stages and Rappaport's modified classification. Advanced disease and non-lymphoblastic histology were prevailing. Chemotherapy was the preferred treatment. Forty-seven patients (54%) are alive with a median follow-up period of 6.2 years. Actuarial survival rate at 5 years is 0.6. Advances in chemotherapy led to an increase in NHL patient's survival. Twenty patients died because of the disease and 21 because of fatal complications. PMID- 1456619 TI - [Biologic rhythm of respiratory rate in the first trimester of life]. AB - This study was designed to address the following objectives: 1) To record the respiratory rate in a population of newborns and infants. 2) To verify the existence of a rhythm in each population group, as well as the organization and maturing process of these rhythms. 3) To determine the possible influence of environmental factors on these rhythms. The study population consisted of the following groups and ages: A) 1 day (21 cases); B) 7 (15 cases); C) 15 (10 cases); D) 30 (17 cases); E) 60 (17 cases); F) 90 (18 cases). Respiratory rate was continuously monitored and recorded, as well as environmental light, noise and temperature. Rhythmometric analysis of the data was done by simple Cosinor test and analysis of variance. The zero amplitude test showed statistically significant differences in the circadian rhythm of groups E and F (p < 0.005). An ultradian rhythm of 3 hours was detected in groups D and F. Environmental factors also showed a circadian rhythm. The appearance of an ultradian rhythm suggest the maturation in a rhythm. To evaluate physiological parameters, reference to time series must be considered. PMID- 1456620 TI - [Clinical profile, course and outcome of gastroesophageal reflux in 10 infants under active medical treatment]. AB - We have studied the clinical profile, cause and outcome of 105 infants with the diagnosis of gastroesophageal reflux. In most cases, pharmacological treatment managed to control the symptoms in 9 out of 10 infants followed in our series. Complications were described in 26.2%, of which esophagitis and chronic respiratory disease were the most common. Corrective surgery of the reflux was indicated in those cases in which pharmacological treatment was not successful. This managed to control the reflux in 90% of all cases. Morbidity was scarce. In all, 75% of the infants were considered to be medically cured within 15.5 months from the time that they were diagnosed and within 18.5 months after the appearance of the first symptoms. PMID- 1456621 TI - [Acute meningococcal disease. Study of auditive sequelae]. AB - We have examined the auditory function in 49 children that have survived an acute meningococcal disease (AMD). Functional auditory exploration consisted of: ABR; tonal liminal audiometry or behavioral audiometry (Peep-show method, Suzuki-Ogiba ROC) depending on the age and collaboration of the patient; and impedanciometrical techniques (tympanometry, ipsi and contra-lateral stapedial reflex). Three months later, altered tests were repeated in patients that had been evaluated at a time greater than 90 days after their first day of hospitalization (n = 18). All tests were repeated in those patients that had been evaluated before 90 days from the first day of hospitalization (n = 31). No transmission or neurosensory hearing impairments were detected as a result of AMD. We consider the absence of neurosensory hearing impairment, despite the presence of significant risk factors, an important finding. These results suggest that the risk of hearing impairment could be reduced to a minimum by the early establishment of antibiotic treatment. PMID- 1456622 TI - [Evaluation of plasma zinc levels in patients with Down syndrome]. AB - Using the atomic absorption spectroscopy technique, the plasma concentrations of zinc were measured in 32 patients with Down's syndrome (DS) and in 44 healthy controls (C). An obvious and significant decrease in the levels of this element was observed in the trisomic subjects (DS:124.5 +/- 21.7 micrograms/dl; C:150.3 +/- 28 micrograms/dl). Additionally, there seemed to be no relationship or dependence between this observation and the age or the institutionalization of these patients. From a detailed analysis of the population studied, it is inferred that together with personal antecedents of repeated infections, there is always a deficit in this element. It is possible that this deficiency might be due to an activation of the zinc dependent enzymatic systems involved in the immune response. PMID- 1456623 TI - [Anthropometric data on newborn infants: comparative study of two ethnic groups]. AB - We have studied the birth weights, obstetrics data and anthropometrical data from 1.157 full-term newborns who were delivered in the Hospital del Insalud-Cruz Roja in Ceuta (Spain). Of these newborns, 489 were of arabic origin and 668 of hispanic origin. Arabic newborns were heavier (3.248 +/- 473 g versus 3.280 +/- 431 g, p < 0.001) and longer (50.2 +/- 1.8 cm versus 49.6 +/- 1.8 cm, p < 0.001) than their hispanic counterparts. These differences were not due to a disproportion in sex or gestational age between the groups. Furthermore, the differences were still present after adjustments were made for maternal age, parity and the mother's smoking habit. Thus, this difference in size at birth between arabic and hispanic newborns could be, at least in part, ethnically related. PMID- 1456624 TI - [Cat scratch disease. An overview based on a case]. PMID- 1456625 TI - [Multiple sclerosis in preschool age. Diagnostic contribution of magnetic resonance imaging]. PMID- 1456626 TI - [VACTERL association: report of two cases, one of them with situs inversus]. PMID- 1456627 TI - [Prevention of chickenpox with acyclovir]. PMID- 1456628 TI - [Gitelman's tubulopathy: deficit of K/Mg transfer]. PMID- 1456629 TI - [Injury to the cervical spinal cord in newborn infants]. PMID- 1456630 TI - [An epidemic of echovirus 4 meningitis: report of nine cases]. PMID- 1456631 TI - [Hypothyroidism and hypercholesterolemia]. PMID- 1456632 TI - [Lafora disease in childhood]. PMID- 1456633 TI - [Congenital familial hemiparesis and familial porencephaly]. PMID- 1456634 TI - Developmental strategies in the analysis of ingestive behavior. PMID- 1456635 TI - Fetal audition. PMID- 1456636 TI - Sexual differentiation of the female spotted hyena. One of nature's experiments. PMID- 1456637 TI - The role of maternal stimulation in the development of sexual behavior and its neural basis. AB - Both sexual differentiation, which is a matter of individual development, and sexual dissimilation, which is a matter of individual differences, result from developmental processes that are open to input from the early maternal environment. There are reliable features in both the dam and the young that ensure that males receive more perineal stimulation from maternal licking than is necessary for survival and normal growth. This stimulation contributes toward the development of masculine sexual behavior and mechanisms in the central nervous system that control copulatory reflexes. Because of differences in signals that they produce, males receive more stimulation than females. This bias in early stimulation accounts for some of the dissimilarity between the sexes in nervous system morphology and behavior. The same processes that produce sex differences can also produce individual differences among males. These differences are likely to have significant functional consequences in rats, a species in which males have a high level of intrasexual reproductive competition. Future research will be directed toward testing this functional hypothesis and toward exploring the extent of stimulative effects on the development of the sexually dimorphic brain regions that function in sexual behavior. PMID- 1456638 TI - Weaning from mother's milk to solid foods. The developmental psychobiology of self-selection of foods by rats. PMID- 1456639 TI - The emergence of behavioral regulation during fetal development. PMID- 1456640 TI - Behavioral and cardiovascular traits. Broken links and new associations. PMID- 1456641 TI - Cellular communication networks. Implications for our understanding of gastrointestinal physiology. PMID- 1456642 TI - Epithelial barrier function to antigens. An overview. PMID- 1456643 TI - Neutrophils, nitrogen oxides, and inflammatory bowel disease. AB - The etiologic factors responsible for IBD remain only speculative. It does appear that the inappropriate activation of the immune system, whether by immune complex deposition, infectious agents or vascular impairment, is important in the pathogenesis of these diseases. Interaction of certain cytokines known to be produced in human IBD with specific immune cells such as neutrophils and macrophages results in the induction of the enzyme NO. synthase with the concomitant release of large amounts of NO.. Nitric oxide is known to mediate many of the pathophysiological alterations associated with IBD including cell injury, intestinal hyperemia and intestinal smooth muscle dysfunction. In addition, NO. is known to decompose in solution to yield potent N-nitrosating agents which will N-nitrosate certain amines to yield potent carcinogenic nitrosamines. Because antioxidants (including 5-ASA) are potent inhibitors of nitrosamine formation, they may prove useful in attenuating the formation of potentially carcinogenic agents in vivo. PMID- 1456644 TI - Intercellular interactions in the recruitment and functions of human eosinophils. PMID- 1456645 TI - Fibroblast modulation of intestinal secretory responses. PMID- 1456646 TI - Peptide growth factors: role in epithelial-lamina propria cell interactions. PMID- 1456647 TI - Epithelial expression of HLA, secretory component (poly-Ig receptor), and adhesion molecules in the human alimentary tract. AB - Epithelial HLA class II is differentially expressed (DR >> DP) only after birth in salivary glands and small intestinal mucosa, in contrast to class I determinants and secretory component (SC) which appear early in gestation. However, there is a brisk postnatal increase in SC expression along with the class II induction, suggesting stimulation by cytokines from activated immune cells. T lymphocytes remain quite scanty in postnatal salivary glands, and the striking SC and class II expression might reflect a synergistic effect of IFN gamma and TFN-alpha on immature epithelial cells. Enhanced epithelial expression of both SC and class II in salivary glands from sudden infant death victims could be the effect of immunostimulation caused by an infectious agent. Strikingly upregulated SC and epithelial class II expression (DR > DP > DQ) is seen in various inflammatory lesions such as obstructive sialadenitis, Sjogren's syndrome, chronic gastritis, and celiac disease. IFN-gamma and TNF-alpha are most likely involved as the expression patterns can be reproduced with these cytokines in vitro on colonic epithelial cell lines. However, these molecules of the Ig supergene family do not show a selective response in epithelia of inflammatory lesions because increased expression is also seen for lysozyme, lactoferrin and some other proteins. ICAM-1 can be upregulated on epithelial cells by various cytokines in vitro although the situation remains uncertain in mucosal inflammation. The expression pattern in IBD is complicated by dysplastic epithelial changes leading to reduced SC levels which may thus, in turn, jeopardize the poly-Ig transport mechanism. Epithelial class II molecules appear to have antigen-presenting properties, but the immunopathologic role of their increased expression in inflammatory disease in terms of induction of autoimmunity and/or abrogation of oral tolerance is a matter of continuing dispute. PMID- 1456648 TI - M cell-mediated antigen transport and monoclonal IgA antibodies for mucosal immune protection. PMID- 1456649 TI - Effector role of the epithelial compartment in inflammation. PMID- 1456650 TI - Mucus: the front line of intestinal mucosal defense. PMID- 1456651 TI - Epithelial proliferation in response to gastrointestinal inflammation. AB - Intestinal inflammation seems invariably to be associated with increased epithelial proliferation. In the small bowel the pathological consequences of this area an increase in the crypt proliferative compartment and a decrease in the absorptive villus compartment, which can lead to malabsorption. In the colon, it is more difficult to examine changes in cell proliferation, but using Ki67, epithelial proliferation has been shown to be increased in ulcerative colitis and parasitic infection. The teleological advantage of increasing epithelial proliferation during intestinal inflammation is presumably in an effort to get rid of parasitized or infected epithelial cells, or to rapidly replace cells which have been lost. Rejection of helminth parasites from rodent small bowel is associated with partial villous atrophy and crypt hypertrophy, which is probably part of the host response making the mucosa inhospitable to the parasites. The short-term nutritional disadvantage of malabsorption is outweighed by the long term advantage of being parasite-free. However, when the intestinal inflammation is elicited by a dietary constituent, the consequences are only pathological. At the moment there is no information as to the mechanisms by which inflammatory cells alter mucosal morphology and epithelial renewal. The restructuring of mucosal morphology in the flat-mucosa involves considerable adaptation of the connective tissue elements of the lamina propria. Whether this occurs in response to changes in epithelial renewal is not known. Finally, it is clear that activated T cells in the lamina propria can produce a flat-mucosa. In diseases such as Trichuris dysentery and ulcerative colitis there is no or very little T cell activation, even though epithelial proliferation is increased. Increased epithelial proliferation therefore may occur in response to different inflammatory stimuli. PMID- 1456652 TI - Epithelial secretory response to inflammation. AB - As suggested by this and previous reviews, the neuroimmunoregulation of intestinal secretion is a complex series of endocrine, neurocrine, paracrine and autocrine interactions between the underlying cells in the mucosa and submucosa and the intestinal enterocyte. Under normal conditions, the balance of each of these systems is delicately controlled, thus allowing for normal, consistent intestinal function. However, when this finely-tuned system is altered, such as in a diseased state, the resultant effect is an amplification of the host defense response. Initially thought to be protective against further insult, this local immune response, if allowed to continue uncontrollably, can exacerbate the disease process. PMID- 1456653 TI - Effect of histamine and other mast cell mediators on T84 epithelial cells. PMID- 1456654 TI - Epithelial secretory responses to inflammation. Platelet activating factor and reactive oxygen metabolites. PMID- 1456655 TI - Concerning prostaglandin D2: forgotten, promiscuous, capricious. PMID- 1456656 TI - Effects of the neuroimmune mediators, peptidoleukotrienes, endothelin, and interleukin-1 on intestinal ion transport. PMID- 1456657 TI - Transepithelial transport of polymeric immunoglobulins. PMID- 1456658 TI - Histamine signals in enteric neuroimmune interactions. PMID- 1456660 TI - Antigen-mediated effects on epithelial function. AB - In summary, immediate hypersensitivity reactions to luminal antigens occur in the intestine and result in pathophysiology including increased permeability and ion secretion. The mechanism involves activation of mast cells with neural amplification (FIG. 5). Released mediators/neurotransmitters may act independently or synergistically on the epithelium to elicit Cl ion secretion. In addition, a cyclooxygenase product of arachidonic acid metabolism, possibly of mesenchymal cell origin, may be a common mediator. However, additional effector cell(s) besides mast cells are undoubtedly involved. This system demonstrates undeniably the concept of neuro-immuno-physiology of gut mucosa. PMID- 1456659 TI - Excitatory and neurotoxic actions of platelet-activating factor on rat myenteric neurons in cell culture. AB - At micromolar concentrations, PAF causes intense excitation and elevation of intracellular Ca in a subset of myenteric neurons. When applied for more than about 10 seconds, these concentrations of PAF kill a subset of myenteric neurons. The excitation and elevation of Ca levels are accompanied by increased membrane conductance and enhanced synaptic activity. The effects of brief applications are reversible, but responses to subsequent applications of PAF are substantially reduced. If such responses can be elicited in enteric neurons by the concentrations of PAF that are generated in vivo, they would account for the potent ability of PAF to evoke neurally-mediated secretory responses in GI tissues. PMID- 1456661 TI - Immediate hypersensitivity reactions in epithelia. Insights from reconstructed tissues. PMID- 1456662 TI - Neuro-modulation of ion secretion by inflammatory mediators. PMID- 1456663 TI - Potent inhibition of gastric acid secretion and ulcer formation by centrally and peripherally administered interleukin-1. AB - IL-1 beta is one of the most potent centrally acting inhibitors of gastric acid secretion in rats. Sites of action have been located in the anterior/preoptic area and paraventricular nucleus of the hypothalamus where other biological activities of IL-1 have also been described. IL-1 beta action is, so far, quite unique to this cytokine and its action is not reproduced by IL-2 or TNF alpha. The IL-1 effect involves prostaglandin pathways and is unrelated to CRF. Similarly, systemic injection of IL-1 induces a long lasting inhibition of acid secretion through prostaglandin-dependent mechanisms. Several findings support the possibility that the effect of systemic IL-1 can be CNS-mediated and/or exerted at the periphery through local release of PG in the stomach. Exogenous IL 1 given into either the circulation or the cerebrospinal fluid also inhibits gastric injury induced by a variety of experimental models (stress, aspirin, ethanol). Such a protective effect is mediated through the inhibition of acid secretion and prostaglandin release, although other mechanisms may also contribute. Whether endogenously released IL-1 beta exerts a protective role in the gastric mucosa is still to be investigated. PMID- 1456664 TI - Intestinal physiology in the parasitized host: integration, disintegration, and reconstruction of systems. AB - As noted in the introduction, the major objective in discussing gut inflammation in the parasitized host is to underscore the difficulty in establishing whether an inflammation-induced change represents a physiological adaptation or maladaptation (Fig. 3). Deciding whether a specific physiological adjustment, even one that contributes to disease, serves a useful function depends on the perspective of the observer who is in possession of information to make a critical judgment. This is like considering adaptations from an evolutionary sense where the significance of a change that evolved as a consequence of natural selection must be interpreted relative to the long-term "goal directedness" of that change, e.g., relative to its contribution to reproductive fitness. Because of the contributions of inflammation to both symptoms of disease and to the development of functional immunity, the parasitized host provides a means whereby both negative and positive effects of mucosal responses can be studied simultaneously. A careful analysis of the consequences of inflammation is important in contemplating the meaning of "neuroimmunophysiology of gastrointestinal mucosa." PMID- 1456665 TI - The regulation of brush border surface area. PMID- 1456666 TI - Immunopathology of NSAID-gastropathy: inhibitory effects of interleukin-I and cyclosporin A. AB - The present study demonstrates that CSA is capable of inhibiting indomethacin induced leukocyte adherence to the vascular endothelium, and can reduce the severity of indomethacin-induced gastric mucosal injury. These results are therefore consistent with the hypothesis that leukocyte (particularly neutrophil) adherence is a critical event in the pathogenesis of NSAID-induced gastropathy. The mechanism through which CSA inhibits leukocyte adherence is not clear, and warrants further investigation. This study also confirmed the protective effects of IL-1 in experimental NSAID-gastropathy, and demonstrates that one of the ways the IL-1 may protect the mucosa is through its ability to inhibit the release of proinflammatory mediators (e.g., PAF) and promote the release of antiinflammatory mediators (e.g., nitric oxide). IL-1 modulated the release of these mediators from peritoneal mast cells at doses in the pg/ml to ng/ml range. IL-1 can inhibit the ability of neutrophils to respond to chemotactic stimuli and can prevent LTB4 induced neutropenia. Inhibition of neutrophil function by IL-1 may therefore account for its ability to reduce NSAID-induced gastric mucosal injury. Whether or not effects of IL-1 on the production of mediators such as nitric oxide and PAF is an underlying mechanism for the inhibitory effects on neutrophil function remains to be determined. PMID- 1456667 TI - Nerve remodelling during intestinal inflammation. AB - The intestinal mucosa contains a dense nerve network and many inflammatory cells, and these may interact through the exchange of regulatory molecules. Evidence suggests that intestinal mucosal mast cells are innervated, and it is known that the density of this cell type changes significantly in nematode-infected rats. Recent data indicates that rat jejunal mucosal nerves remodel after Nippostrongylus brasiliensis infection, with degenerative and regenerative phases during the acute and recovery stages of inflammation. Seven weeks postinfection there is a net increase in the density and number per villus of mucosal nerves. These changes suggest that mucosal nerves exhibit structural plasticity in inflamed tissues, which must impact on interactions between the enteric nervous system and other mucosal elements in disease. PMID- 1456668 TI - The movement of solutes and cells across tight junctions. AB - The TJ is a highly dynamic rate-limiting barrier for passive transepithelial solute flow. It is not only physiologically regulated but is modulated in various disease states as well. Such modulations occur as a result of epithelial cell interactions with immune cells or immune cell products and thus epithelial barrier function appears to be regulated in disease states. PMID- 1456669 TI - The lamina propria: a dynamic, complex mucosal compartment. An overview. PMID- 1456670 TI - T lymphocyte subsets, cytokines, and effector functions. PMID- 1456671 TI - Regulation of macrophage infiltration and activation in sites of chronic inflammation. PMID- 1456672 TI - [Cochlear implants in children]. AB - The development of surgically implantable hearing aids that are placed directly in the cochlea where they send electrical impulses to the cochlear nerve is a major break-through for patients whose hearing loss is so severe as to make conventional electroacoustic hearing aids ineffectual. Initially used only in adults, this method has gradually been extended to pediatric patients. To benefit from a cochlear implant, the patient must fulfill a number of criteria which are specified in this article. Following preoperative investigations, the decision is taken during a meeting of all the care providers involved, i.e., the surgeon, ENT phoniatrist or audiophonologist, hearing aid specialist, special education provider, speech therapist, psychologist, and other members of the health care staff. Team work is thus essential both before and after the procedure. The implant selected can be intracochlear or extracochlear and single-channel (one electrode) or multi-channel (several electrodes). Each team selects the implantation technique and type of implant they use according to their preferences and specific criteria. The authors use a multi-channel intracochlear system except in the rare instances where complete ossification of the cochlea requires use of an intracochlear mono-channel system. They have inserted implants in 29 patients to date. The cochlear implant has unquestionably had a significant impact of the life of these patients. PMID- 1456673 TI - [Nasal polyposis in children. Diagnostic and therapeutic problems]. AB - Nasal polyposis in an infrequent condition in children and may occur as part of a variety of diseases. Treatment is difficult and often yields disappointing results. The purpose of this paper is to review the diagnostic problems raised by nasal polyposis and to analyze current surgical approaches. Twenty-seven patients with a mean age of 12 years, including 12 with nasal polyposis as part of another disease state (cystic fibrosis in 10 and Woakes disease in 2) and 15 with idiopathic nasal polyposis, underwent endonasal ethmoidectomy. The decision to perform this procedure was based on severity of initial clinical symptoms, lack of improvement under medical treatment, and availability for close postoperative follow-up. Twenty-six patients were followed-up for a mean period of three years ad a half. Complete recurrence occurred in 15% of patients and partial recurrence in 8%. In all the other cases, the ethmoidal cavity was satisfactory and nasal symptoms resolved completely. Etiopathogenic aspects of nasal polyposis are reviewed, as well as the therapeutic approach according to whether or not the disease occurs as part of another syndrome. PMID- 1456674 TI - [Choanal atresia: management and surgical treatment. Study of 50 cases]. AB - Diagnosis of choanal atresia should lead to multidisciplinary investigations to look for other malformations which may or may not be part of the CHARGE syndrome. These concomitant defects have an adverse effect on prognosis in patients with choanal atresia. They seem to be more common in patients with bilateral choanal atresia due to a bony septum. Local investigations include nasal fiberoptic endoscopy to obtain a direct view of the atresia and a CT scan study to determine the type of obstruction. In neonates, treatment rests on transnasal perforation of the septum followed by stenting for four to six weeks. However recurrence is common and requires subsequent use of another therapeutic procedure. In patients with failed transnasal perforation or unilateral choanal atresia discovered at a later age, surgery through the palatal route seems to be virtually radical and can be carried out from eight months of age. Recently developed CO2 laser therapy is, in the opinion in of the authors, an elegant and simple means for transnasal treatment of fibrotic restenosis which, in many cases, obviates the need for transpalatal surgery. PMID- 1456675 TI - [Bacterial epidemiology of acute otitis media]. AB - Since the middle of the 1980's, Haemophilus influenzae is the most common bacterial species responsible for acute otitis media in France, followed by Streptococcus pneumoniae. Haemophilus influenzae has maintained its leading position since 1985, but the rate of pneumococcal acute otitis media is increasing fairly steadily. The other recent change with regard to the distribution of bacterial agents is the emergence, four years later than in North America, of Branhamella catarrhalis which currently accounts for 10% of cases of acute otitis media. Modifications in the behavior of microorganisms in relation to antimicrobials usually given to treat upper respiratory tract infections have occurred. Staphylococcus aureus and Branhamella catarrhalis have always exhibited marked resistance to ampicillin due to the production of beta-lactamases. Resistance of Haemophilus influenzae to ampicillin has been increasing gradually since 1985, again with a lag of a few years as compared with the United States; at present, this form of resistance is seen in approximately 35% of strains. More recently in France, 20% of pneumococcal strains recovered from middle ear pus have been shown to have abnormal susceptibility to penicillin. These changes in the behavior of the two main pathogens, i.e., Haemophilus influenzae and Streptococcus pneumoniae, require implementation of rigorous multiregional epidemiologic surveillance programs and may justify reappraisal of current therapeutic approaches. PMID- 1456676 TI - [Current therapeutic approach to cervicofacial lymphangiomas in children]. AB - Twenty-four cases of cervicofacial lymphangioma treated between 1984 and 1991 are reported. The therapeutic approach is discussed. Because the therapeutic problem depends on whether or not the airways are involved, an endoscopic evaluation and a CT scan study should be included in the workup. In the five patients with limited lymphangiomas, complete surgical exeresis was feasible and yielded good results. Sclerosing injections are an alternative to surgery in this situation. In patients with pharyngeal or laryngeal infiltration or involvement of the mediastinum, the prognosis is extremely grim and surgery is still the mainstay of therapy despite the potential for recurrence due to the fact that only incomplete exeresis can be performed. Tracheostomy was required in two patients. PMID- 1456677 TI - [Management of caustic burns of the esophagus in children]. AB - The authors describe their therapeutic approach to caustic burns of the esophagus in pediatric patients. Initially, early endoscopic evaluation is carried out under general anesthesia using a stiff tube then a fiberoptic endoscope. During this procedure, severity of esophageal damage is determined: stage I: mild burn requiring no treatment; stages II and III: severe burn with a risk of subsequent esophageal stricture requiring insertion of a nasogastric stent. A repeat endoscopy is performed after approximately 25 days to evaluate healing. If healing has occurred, the nasogastric tube is removed and dynamic esophagography is performed 2 to 7 days later. Patients with strictures should be treated with repeated endoscopic dilatation at gradually increasing intervals. Surgery is indicated only in patients with complications or multiple strictures after failure of dilatation; trans-mediastinal colon esophagoplasty with removal of the burned esophagus is the method of choice. PMID- 1456678 TI - [Deafness screening in children by otoacoustic emissions. Current data]. AB - Hearing impairment should be detected in early childhood. Among available screening techniques, acoustic oto-emission testing is a rapid, reliable, noninvasive method which specifically investigates peripheral hearing but does not provide data on auditory nerve centers. This functional test should be carried out within a few days of birth in infants with risk factors for hearing impairment. PMID- 1456679 TI - [Severe aplasia of the ear: management and surgical indications]. AB - Severe aplasia of the ear raises both a cosmetic and a functional problem. Surgery is often performed starting at four or five years of age but early management is essential. The need for a hearing aid should be evaluated at the age of six months. At birth, the infant should have investigations for concomitant malformations, which are common, and for etiologic factors. Functional surgery to create a canal, tympanic membrane, and chain of ossicles should be performed only in bilateral forms. Satisfactory cosmetic results can be achieved by cartilage autografting according to Brent's technique. PMID- 1456680 TI - [Current therapeutic indications in laryngeal stenoses in children]. AB - Among pediatric patients with laryngeal stenosis, acquired forms are now more common than congenital forms. External surgery is not always warranted except in complete or tight obstructions. After establishing the diagnosis by endoscopy, consequences on respiration and phonation should be assessed before deciding on the most appropriate treatment: abstention, medical therapy, endoscopic treatment, or surgical treatment by the cervical route. Surgical laryngoplasty techniques have changed radically over the last twenty years. The Cotton procedure is the most widely used. Another available method is the cricoid-split technique. These laryngoplasty procedures can be performed from birth and tracheostomy is now warranted only after failure of initial surgery. PMID- 1456681 TI - [Syndrome of obstructive sleep apnea in children]. AB - Sleep apnea syndrome (SAS) in children has been identified only recently. Its incidence is unknown but seems to be rising. The cause is usually an obstruction (enlarged tonsils) that alters the fragile physiologic mechanisms responsible for maintaining the upper airways open when the child is sleeping. Diagnosis of SAS rests on clinical findings. The parents should be questioned as to the frequency over time of the various symptoms, of which most occur during the night: snoring, difficult breathing, respiratory pauses. Sleep polygraphy studies are indicated only in specific situations. The main cause is enlargement of the adenoids and tonsils. Cardiovascular complications may develop; weight gain and statural growth, psychomotor development and development of the face may be altered. Chronic snoring without apneas should be considered as a form of SAS. Treatment rests mainly on surgery (removal of the adenoids and tonsils). PMID- 1456682 TI - [Vertigo in children]. AB - The main difference between childhood and adulthood vertigo is that the evaluation of symptoms and examination pose special challenges in pediatric patients, depending on age. Vertigo in pre-teenage children is similar to vertigo in adults. In contrast, although benign paroxysmal vertigo, vestibular neuronitis, and Meniere's vertigo occur in children, the distribution of these conditions is different from that seen in adults. After vestibular and cochlear investigations as well as a CT scan or MRI study to outrule a tumor of the posterior cerebral fossa, the diagnosis of vestibular vertigo is established. Often, the diagnosis proposed cannot be considered as final and requires reappraisal according to the long-term course. Collation of case-reports with highly accurate documents is essential in order to strive to develop more satisfactory approaches. PMID- 1456683 TI - [Why and how should serous otitis media be treated?]. AB - Serous otitis media is an extremely commonplace condition in pediatric patients and tends to resolve spontaneously. Only some forms warrant treatment. Indications for treatment include frequent superinfections, lasting hearing impairment with adverse consequences on socialization, or debilitation of the tympanic membrane carrying a risk for the ear. Tympanostomy tubes are a palliative treatment for serous otitis which restores hearing within a few hours and eliminates unfixated retractions of the tympanic membrane within a few weeks. Tympanostomy tubes may lead to complications including otorrhea and perforation of the tympanic membrane and should therefore be used only in patients with severe otitis media. Etiologic treatment of serous otitis rests on restoration of satisfactory nasal ventilation (education to improve nose-blowing, adenoidectomy), improvement of eustachian tube patency (corticosteroids), and modification of the characteristics of middle ear secretions (mucolytic agents and mucomodifying agents). PMID- 1456684 TI - [Cancer of the stomach: the Japanese example]. PMID- 1456685 TI - [Cancer of the stomach: for a revised strategy]. AB - The "revisionist" approach to therapy of gastric cancer needs a previous demonstration of the qualitative comparability of Japanese and western treatments of gastric adenocarcinoma. Early gastric cancer is far more common in Japanese than in Occidentals, but its character is the same, and for identical stages and treatments, the prognosis is the same. But many western studies show serious methodological deficiencies (staging, anatomopathological examination...), as well as a serious lack of interest in adjuvant therapy, a potential source of progress. We propose a 4-point therapeutic approach inspired by the Japanese example: a greater methodological rigor, standardization of lymphadenectomies, the definition of therapeutic subgroups to receive optimal treatments, the development of new adjuvant treatments. PMID- 1456686 TI - [Value of a "floppy" Nissen in the treatment of gastroesophageal reflux. Apropos of 117 cases]. AB - The Nissen fundoplication is the most widely used antireflux procedure. However this operation is associated with several specific complications. To prevent these complications, an alternative antireflux procedure ("floppy" Nissen) has been designed. This investigation was conducted to investigate the effects of the floppy Nissen performed on 117 patients, between 1978 and 1990. Indication for surgery was the endoscopic discovery of stage I and II oesophagitis (59 cases), III and IV oesophagitis (25 cases) or an associated disease (gallstones: 25 cases, duodenal ulcer: 8 cases), pH monitoring used preoperatively in 47 cases showed an important reflux in 33 cases (70%). Preoperative manometry exploration (71 cases) showed a low pressure of the low oesophageal sphincter (LOS) in 63 cases (89%). The "floppy" Nissen procedure was performed over a length 4 to 6 cm. The folds of the diaphragm were closed back behind the oesophagus in 40 cases. During the postoperative period the pH-data were restored to normal range in 73% (18/26 cases), and the value of the LOS was restored in 74% (19/26 cases). The mean duration of clinical follow-up study of 99 patients was 3.22 years. Improvement in clinical symptoms was noted for 86%; 13% had specific Nissen complications (9 gall-bloat syndrome, 4 intermittent dysphagia). Six patients had to be reoperated. This technique allowed good control of the reflux symptoms, with a low incidence of mechanical complications. PMID- 1456687 TI - [Prognostic incidence of blood transfusion in 753 patients operated for colorectal adenocarcinoma]. AB - Do transfusions have a deleterious effect on the survival after surgery for colorectal carcinoma (CRC)? Among 1,221 patients operated on for a CRC between 1969 and 1988, 753 patients having undergone a curative surgical procedure with a follow-up of at least six months were evaluated retrospectively. 134 patients (17.2%) did not receive any transfusion; the others 619 (82.80%) received transfusions including 150 with packed red blood cells only. Transfused and non transfused patients were compared. Among the classical indicators for disease free survival, the only valuable parameter was the pathological classification, but it was not discriminant between transfused and non transfused patients. Prognostic value of transfusions were evaluated with regard of the components and the quantity of transfused items, the time of transfusions (either per- or perioperative), the surgical procedures and the tumor location on colon and rectum. The 5 years survival of transfused patients was less than for non transfused patients (56.3% versus 61.7%, p > 0.05 NS), but only the transfusions of more than 5 packed red blood cells worsened significantly the prognostic. (5 years chi 2 = 5.7; p < 0.02). Adjustments with pathologic analysis and time evolutive indications for transfusions did not alter those results. These results point the fact that transfusions could influence survival after surgery for CRC and stress us to limit reasonably transfusions. PMID- 1456688 TI - [Minimal intestinal preparation before colectomy for cancer. Experience of 189 cases]. AB - 189 cases of colectomy for cancer have undergone limited bowel preparation by one or two enemas the day before surgery. The anastomosis has been performed manually with a continuous suture of resorbable material. Hospital mortality is 1.6% for the whole series and limited to 0.5% for elective resections despite the old age of the patients included (70.6 +/- 11 years, with 40.7% more than 75 years). Morbidity rate is 13.9% and of 2.6% for local septic complications. No clinical anastomotic dehiscence was demonstrated. From these results, poor local bowel preparation does not appear to be a risk factor of colectomy for cancer. PMID- 1456689 TI - [Postoperative morbidity and mortality of infectious complications of colonic diverticulosis: multifactorial study]. AB - The objective of this study was to determine parameters influencing the mortality due to postoperative adverse events, by taking into account surgical techniques and many other perioperative parameters. From 1967 to 1989, 83 patients were operated for pericolic abscess (level 1, n = 22), pelvic abscess (level 2, n = 38) purulent peritonitis (level 3, n = 16) and fecal peritonitis (level 4, n = 7). Surgical techniques were: first colostomy with drainage (n = 21), first resection without immediate anastomosis (n = 34), and first resection with immediate anastomosis (n = 28). The overall complications were 51% (n = 42) with a mortality of 28% (n = 23). During univariate analysis, variables linked to postoperative complications were neurologic events (p < 0.0001), cirrhosis (p = 0.01), current treatment by steroids (p = 0.007), infectious level (p = 0.002), first colostomy (p = 0.005) and first resection with anastomosis (p = 0.007). Postoperative mortality was linked with neurologic events (p < 0.0001), age (p = 0.005), infectious level (p = 0.04), first colostomy (p = 0.005), and first resection with anastomosis (p = 0.0012). Logistic regression determined 3 independent variables influencing complications: neurologic events (p < 0.0001), first colostomy (p = 0.01), and infectious level (p = 0.002). The mortality determined by multivariate analysis was dependent on 3 variables: neurologic events (p < 0.0001) first colostomy (p = 0.007) and age (p = 0.01). The adjusted relative risk was 17 for neurologic events and 6 for first colostomy. PMID- 1456690 TI - [Validation of the measurement of hepatic volume by three-dimensional computed tomography]. AB - The aim of this work was to verify experimentally the reliability of 3D CT scan in measuring hepatic volumes. Eight livers were dissected from corpses. The referring liver volume was determined by measure of its hydric shift. The correlation coefficient R was 0.93 (p < 0.001) on 5 mm/5 mm 3D sections, 0.92 (p < 0.001) on 10 mm/10 mm 3D sections and 0.94 (p < 0.0006) on 5 mm/10 mm 3D sections. The paired t-test also showed a 5% risk correlation between the two measurements. Although in vivo imaging is slightly different from in vitro, 3D CT scan seems to be a reliable method to determine an hepatic volume without increased X-ray irradiation. PMID- 1456691 TI - [Acute hepatic artery thrombosis in pediatric liver transplantation: surgical thrombectomy and in situ fibrinolysis]. AB - In pediatric liver transplantation, hepatic artery thrombosis usually leads to graft loss, early due to hepatic necrosis when it occurs during the first week following the transplant procedure, or later due to biliary complications. Liver retransplantation is the usual attitude. However, urgent surgical hepatic arterial thrombectomy to restore the blood flow can be successful when early diagnosis is made with Doppler ultrasound examination and angiography. Four hepatic arterial thrombectomies were performed as an emergency with additional intra-hepatic arterial fibrinolytic treatment, in three children, 1.5, 3 and 5.5 years of age. Mean duration between the first signs of hepatic artery thrombosis and thrombectomy was 16 hours. None of the children had an urgent liver retransplantation. A complete success was obtained in one case, with normal liver function tests and patent hepatic artery on the Doppler ultrasound examination at the present time. In the two other cases, hepatic artery thrombosis recurred, in spite of repeated thrombectomy in one case; following this attempt complications of hepatic artery thrombosis occurred in the two patients: ischemic necrosis of the left lobe (1 case), biliary leak (1 case) and stenosis of the common bile duct (2 cases). A complete success in one case and a partial success in the two others lead us to advocate urgent thrombectomy and in situ fibrinolytic treatment when early diagnosis of hepatic artery thrombosis is made. PMID- 1456692 TI - [Cholecystectomy by celioscopy: indications and safety of the method. Apropos of a consecutive series of 300 patients]. AB - We performed a laparoscopic cholecystectomy in 300 patients with gallstone disease complicated or not. The rate success was 97%, however involved the pathology might be. Indeed, 15% of the patients had an acute cholecystitis (10% catarrhalis, 5% empyema). Twenty-four patients with common bile duct stones had a complete endoscopic management of the biliary disease: endoscopic sphincterotomy and laparoscopic cholecystectomy. Operative mortality was absent and overall morbidity was 3.7%, exclusively minor. PMID- 1456693 TI - [Role of resection of the celiac plexus in the analgesic treatment of pancreatic cancers]. AB - The aim of this study was to evaluate the pain relief related to resection of the celiac plexus in pancreatic carcinoma. This technique was attempted in 26 consecutive patients and performed in 23 (feasibility: 88%), whose mean age was 64 years. Before surgery, patients were divided into two groups: patients not treated by narcotic analgesics (group 1, n = 10) and patients treated by narcotic analgesics (group II, n = 13). Surgery was indicated in 22 patients for pancreatic resection or by-pass, and in 1 patient for pain relief after an unsuccessful per-cutaneous celiac plexus block. Resection of the celiac plexus was always performed via a trans-peritoneal approach, after mobilization of the head of the pancreas and the duodenum. Only the right half of the celiac plexus was resected in 4 patients (17%) due to technical difficulties. Pathologic examination was performed in 16 patients (8 patients from each group) and neoplastic involvement was observed only in 3 patients of group II. There was no operative death. Two complications related to this method occurred (9%). One patient developed a chylous ascites and was treated conservatively. In a second patient, an occlusion of the celiac trunk was complicated by infarction of the spleen and of the left lobe of the liver; this patient was reoperated and his subsequent post-operative course was uneventful. In group I, eight patients (80%) did not require narcotic analgesics after resection of the celiac plexus. Two failures occurred, one immediately after surgery and one delayed. In group II, seven patients (53%) did not require narcotic analgesics; 6 of these 7 patients died. Six failures occurred, 4 early after surgery and 2 delayed. Three of the 4 early failures occurred in patients who underwent resection of the right half of the celiac plexus. The authors concluded that resection of the celiac plexus seems to be an effective pain treatment in pancreatic carcinoma. However, resection must be bilateral to provide analgesia. Specific morbidity of this technique may lead to the use of non-surgical methods if surgery is not indicated for pancreatic resection or by-pass. PMID- 1456694 TI - [Left pancreatectomy with preservation of the spleen without its pedicle. Apropos of 13 cases]. AB - Overwhelming post splenectomy infections in childhood were first described by King and Shumaker in 1952. This septic risk, although a matter of controversy, also exists in adults. Thus, splenic conservation must become a surgical concern in left pancreas resections for benign or traumatic diseases. The authors report their experience with a simplified procedure in which the splenic pedicle is resected "en bloc" with the left pancreas. This technique has been employed in thirteen patients, in whom spleen could be preserved in twelve, without operative mortality and a low morbidity rate. PMID- 1456695 TI - [Pancreas divisum, chronic pancreatitis and diabetes mellitus. Improvement by pancreaticojejunostomy]. AB - The relationship between pancreas divisum and chronic pancreatitis is controversial. We report the cases of two patients aged 40 and 53 years suffering from recurrent pancreatitis and known to have histologically proven idiopathic chronic pancreatitis. One patient had insulin dependent diabetes. Pancreatography demonstrated in these two cases a pancreas divisum with a dilated dorsal pancreatic duct. A pancreatico-jejunostomy was performed, associated in one case with splenopancreatectomy for pseudo-cyst. With a follow-up of 32 and 78 months, both patients were free of symptoms and the diabetic patient had normal blood glucose levels with diet alone. The clinical history of the patients suggests a relationship between pancreas divisum and chronic pancreatitis and that pancreatico-jejunostomy may improve pancreatic pain and pancreatic function. PMID- 1456696 TI - [A direct approach and a crease-resistant prosthesis: two simplifications of subperitoneal hernioplasty]. AB - With experience of six already known techniques, the authors have developed a personal procedure combining three main principles: 1) large and direct exposure of the preperitoneal space, 2) the mesh, supple but not soft, needing no fixation, 3) outline of this mesh adapted to the concave shape of the pelvic wall, and avoiding the risk of a ventral hernia. The original points of this technique are the following: approach along the lateral border of the rectus muscle through its sheath, the initial exposure of the iliopsoas muscle and retropubic space, and the cutting of the mesh extending far beyond the borders of the inguinal and femoral orifices, with a flap reinforcing the posterior aspect of the rectus muscle. One hundred and two consecutive patients (173 hernias, 48 recurrences) were operated upon, and all but two were followed for a mean period of 36.8 months. Morbidity was low, with no prosthesis infection, and there was no recurrence or incisional hernia. The authors emphasize the simplicity and the rapidity of this technique, without advocating it as a routine operation, since it carries, like all prosthetic techniques, the potential for sepsis and preperitoneal fibrosis. PMID- 1456697 TI - [Cystadenocarcinoma with peritoneal involvement (pseudomyxoma peritonei). Is surgical resection alone sufficient?]. AB - We present our experience of 10 cases of pseudomyxoma peritonei treated in our regional hospital between 1978 and 1992. We note the rarity of this disease; the catastrophic macroscopic appearance may mislead the in experienced surgeon. Preoperative diagnosis is usually easy when confronted with a mass in an ascitic abdomen, with the help of ultrasonography and CT-scan, and above all after abdominal puncture which produces pathognomonic gelatinous fluid. Most cases are derived from the ovary and appendix. Treatment is surgical and aggressive; we adopt the protocol proposed by Sugarbaker which combines repeated surgery and local and systemic chemotherapy. The relatively good survival, even in the malignant cases, seems to be improved by this treatment. PMID- 1456698 TI - [Late revascularization of the renal artery: what are the prognostic criteria?]. AB - Two patients with non functioning silent kidney on excretory urography and renal artery occlusion on angiography, underwent renal artery revascularization without severe hypertension or renal failure. Angiographic appearance of collateral circulation, histologic evidence of intact viable glomeruli and a normal sized kidney are necessary for successful results. Renal blood flow was restored in the two patients but one had slight return of function and the other patient showed no evidence of improvement. Both patients presented criteria for revascularization. The first case was a minor success on the renal scintigraphy. The return of renal function did not occur in the second case because of preexisting renal pathology. We therefore recommend histologic examination before every renal artery revascularization for chronic occlusion. PMID- 1456699 TI - [Primary hyperparathyroidism: etiology, physiopathology and natural history]. PMID- 1456700 TI - [Primary hyperparathyroidism in children]. AB - Primary hyperparathyroidism in children is an extremely rare condition. Slightly more than a hundred cases have been published in children or adolescents aged under 16. Forms with a neonatal presentation, the most rare, should be viewed apart since they rapidly become life-threatening. They involve hyperplasia of the chief cells of the parathyroid glands. Treatment is always surgical and should be rapid, consisting of total parathyroidectomy with autotransplantation. Primary hyperparathyroidism in older children more closely resembles that seen in adults. Sporadic forms are most often due to an adenoma and familial forms, which may occur alone or within the context of a polyendocrine syndrome, are most often due to hyperplasia. Treatment consists of parathyroidectomy, the extent of which depends upon the familial context, visual investigative findings and results of frozen section histology at the time of exploratory cervicotomy. Regardless of the age of the child, family investigation is always required to detect primary hyperparathyroidism occurring in the context of a hereditary disorder. PMID- 1456701 TI - [Early weight-bearing after osteosynthesis by THS hip screw in cervico trochanteric fractures]. AB - A second generation hip screw was designed in the laboratory to allow unlimited immediate weight-bearing in elderly patients with cervico-trochanteric fractures. The use of this device in 300 operated patients demonstrated that it provided the same capacity for weight-bearing as total hip prostheses, but with a lower morbidity and better and longer lasting functional results. Thus, in patients with a mean age of 77 years, one half of whom suffered from an unstable fracture: the operation was minimally traumatic (reduction on an orthopaedic table, no surgical access to the fracture site, operating time less than one hour); complications were consequently rare (no deep sepsis, no dislocation) in contrast with 5 to 10% of deep sepsis or dislocation with prostheses; early unlimited weight-bearing was permitted by the 5th day in every case and was achieved by the 10th day in more than 80% of cases (30% of whom were able to walk unassisted with crutches); an essential point, the design of the material prevented dismantling on weight-bearing and preserved the morphology of the hip (telescoping of the fracture site never exceeded 20 mm, mean:11 mm). Consolidation was obtained in every case by 6 to 8 weeks. The mortality at 3 months was identical to that observed with prostheses (18%, related to physiological age). The length of hospital stay and the duration of rehabilitation were considerably shortened, as 37% of patients returned to their previous residence by the 45th postoperative day. This resulted in a marked saving in medical costs for each patient (as patients previously returned home after an average of 145 days).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456702 TI - Faltin Lecture 1991. Faltin, the urologist. PMID- 1456703 TI - Results of surgical treatment of patients with Crohn's disease. AB - A follow-up study of 98 patients suffering from Crohn's disease was performed to evaluate the recurrence rate of the disease and the patients' ability to cope socially with this chronic disease. Eight patients were decreased and one had emigrated, thus 89 of the patients were contacted. Two of the patients had died of Crohn's disease and another two had died of adenocarcinoma of the large bowel involved in Crohn's disease. 83% of the patients had been operated on. The cumulative rate for recurrences resulting in reoperation using the life table method was 34% at 10 years and 55% at 20 years. Even after an enterostomy, the patients who had only large bowel involvement had the best quality of life and were most able to work. On the other hand, due to the higher recurrence rate, operated patients with both small and large bowel involvement found it most difficult to cope with the disease. PMID- 1456704 TI - Characteristics of jaundice and cholestasis in a Finnish population. AB - A prospective study of a Finnish population of about 250,000 patients with jaundice or unjaundiced cholestasis was carried out. During a two-and-a-half year period altogether 343 patients entered the study. The male/female ratio was 46%/54%. The mean age was 64.9 years (range 19-92). Extrahepatic obstructive diseases constituted two-thirds of the cases both in the jaundiced and unjaundiced cholestatic patient groups. The leading extrahepatic diseases causing jaundice were gallstone disease (61%) and pancreatic carcinoma (19%). Among the nonobstructive intrahepatic diseases causing jaundice, the most frequent diseases were alcoholic liver disease (32%) and viral hepatitis (21%). In patients with unjaundiced cholestasis, the spectrum of diseases resembled that of the jaundiced patients, gallstone disease and pancreatic carcinoma being the largest disease groups. In conclusion, extrahepatic obstructive processes seem to be the major aetiology of jaundice and unjaundiced cholestasis in our study population. PMID- 1456705 TI - When is routine operative cholangiography necessary? An evaluation of 200 consecutive patients operated on for gallbladder stones. AB - Operative cholangiography (OC) was performed during open standard cholecystectomy in 195 of 200 consecutive patients. The cholangiography was considered suspicious for choledochal stones in 28 patients (14%). Both choledochotomy and choledochoscopy were carried out. Stones in the biliary tree were found in 17 patients and in 11 cases choledochotomy was negative. Cholecystectomy was performed on an emergency basis in 46 patients, 15 of them underwent choledochotomy and in 11 (24%) bile duct stones were found. In 154 electively operated patients six (4%) had choledochal stones. Based on preoperative history choledochal stones were suspected in 30 electively operated patients but only eight had stones in the biliary tree at the time of operation. The percentage of false positive cholangiograms was 6% in the whole material, and unsuspected choledochal stones were diagnosed in 5% respectively. It is recommended that operative cholangiography should be performed routinely in patients subjected to emergency cholecystectomy. In elective operations selective use is acceptable. PMID- 1456706 TI - Results of 500 general surgery patients operated on in the ambulatory surgery unit. AB - This study examined the outcome of 597 general surgery operations performed on 500 patients in the ambulatory surgery unit of the University Hospital of Kuopio between November 1989 and May 1990. Endoscopies were excluded from the study. Spinal (41.0%) and local infiltration (31.2%) were the most often used forms of anaesthesia. During anaesthesia 15.8% of patients required treatment for hypotension, and 13.6% for bradycardia. Of the 351 (70.2%) patients, who returned the one month follow-up questionnaire, 41 (11.7%) had visited a doctor postoperatively. The main reasons for this visit were pain in 41 (100%), minor bleeding in 24 (58.5%) and inflammation in 16 (39.0%) patients. No deaths or other major complications were observed. 92% of the patients were satisfied with the treatment and anaesthesia. PMID- 1456707 TI - Recurrences after inguinal herniotomy in children. Long time follow-up. AB - Three hundred consecutive children all under 18 years of age were treated for inguinal hernia by herniotomy by the same surgeon from 1970-1985. Hernioplasty was not performed. Seven patients had a recurrent hernia, i.e., a cumulative recurrence rate of three per cent after a median follow-up of 12 years (range 5 19). Five of seven (71%) recurred within five years after the operation, while only two recurred from the 5th to the 15th year. Long term follow-up is necessary to assess incidence of recurrence after inguinal herniotomy in children. PMID- 1456708 TI - Bronchoscopic laser photodestruction of benign tumours in the trachea and large bronchi. AB - Potentialities and results of laser bronchoscopic surgery of exophytic benign tumours of the trachea and bronchi are described. The material includes 37 patients (33 men and 4 women) aged 28-69 (mean age 51 years). Tumours were removed by the Nd-YAG laser. In six patients laser photodestruction was combined with electrosurgery. In 31 patients manipulations were done via bronchofiberscope under local anaesthesia and in six patients via a rigid bronchoscope under general anaesthesia. Complete removal of pathologic tissues was achieved in all patients. During 1-5 years of follow-up none of the patients developed recurrent tumours. PMID- 1456709 TI - Hip fractures in urban population in Finland. AB - We studied prospectively the occurrence of hip fractures among the over 49-year old urban populations (n = 88,206) in the cities Tampere, Jyvaskyla and Kotka in 1989 and compared the results with a parallel Scandinavian multicentre study. During 1989, there were 266 inhabitants who were treated for a hip fracture, 213 of them were women. Women had in 132 cases a femoral neck fracture and in 81 cases a trochanteric fracture, and the corresponding numbers for men were 22 and 31. Among women, the total hip fracture incidence in Jyvaskyla (n = 22) was the lowest when compared with the ones in Tampere (n = 47) and Kotka (n = 36). These incidences were on average lower than in the other Scandinavian cities studied in parallel. The all over ratio of femoral neck/trochanteric fractures was 1.1 in Tampere, 3.0 in Jyvaskyla and 2.2 in Kotka and in Tampere, women had 9.3 times more femoral neck fractures than men. Our study showed that in Finland in three major cities the hip fracture incidence was lower than what has been similarly registered in corresponding urban populations in other Scandinavian countries. We also point out that the relative part of trochanteric fractures appears to be increasing. PMID- 1456710 TI - Platelet activation during acute phase after multiple trauma. AB - The acute phase after multiple trauma is associated with both thrombotic phenomena and a bleeding diathesis. To evaluate the activation of platelets, beta thromboglobulin (BTG) in plasma and serum and thromboxane B2 (TxB2) in serum were measured in 14 patients with multiple trauma. BTG in plasma was significantly increased on days 1, 2 and 10 to 14 after the trauma. The highest median value 90 micrograms/l was measured on day 1. BTG in serum was significantly reduced 1 to 7 days after the trauma (median levels 4450-9100 micrograms/l). TxB2 was significantly reduced (median levels 18-97 ng/l) on days 1 to 14. The increased plasma levels of BTG is due to the posttraumatic activation of platelets in vivo. The reduced levels of serum BTG and TxB2 reflect the deficient functional capacity of circulating platelets to respond to extreme stress. Therefore, platelet count alone may correlate poorly with the haemostatic potential and may underestimate the need of platelet transfusions. PMID- 1456712 TI - [Stop to medicine as a spectacle!]. PMID- 1456711 TI - Primary malignant schwannoma of the small bowel. AB - Primary malignant schwannoma of the small intestine is an extremely rare disease. We report a primary malignant intestinal schwannoma of the small bowel in a 66 year-old woman, who was admitted to the hospital because of fatigue and anaemia. On clinical examination there was a solid mass at the abdomen. Ultrasound scanning showed an abdominal tumour. Computed tomography showed a mass in the area of the pancreatic tail involving the small intestine. At laparotomy a 10 x 10 cm tumour was found in the proximal jejunum, and 50 cm of the small intestine was resected. The histology of the lesion corresponded to a malignant intestinal schwannoma. The results of previous studies and of our report suggest that the diagnosis of malignant intestinal schwannoma may be difficult, and to exclude malignant conditions laparotomy and surgical excision of the tumour are adequate in the management of this type of lesion. PMID- 1456713 TI - [Periprosthetic membrane island flap with axial pedicle. Experimental study on the effect of time and expanded volume]. AB - This experimental study, conducted in the rat, assessed the influence the volume of expansion and time after expansion on the vascularised area of a periprosthetic membrane axial pedicle (epigastric) expanded island flap. 15 Wistar rats were operated on and divided into 3 series according to the expanded volume (20 cc, 40 cc) and the time (1, 2 months). The membrane vascularisation derived from the pedicle was study by microradiography based on geometric parameters. At equal times, the volume essentially increased the length of the pedicle and had little effect on the vascularised area. For equal expanded volumes, increasing latency time increased the length and especially the width of opacification derived from the pedicle. The periprosthetic membrane axial pedicle island flap is an experimental entity whose vascularised area, obtained after a certain amount of expansion, is influenced more by time than by the volume of expansion. PMID- 1456714 TI - [Refinement of partial and total reconstruction of the nose]. AB - In this surgical field, sophisticated refinements of the complex structures of the tip, the alae and the columella are required to achieve a corrected rather than a reconstructed appearance of the nose. The conventional corrective rhinoplasty should complete the reconstructive work. Apart from skin grafts and composite grafts for small repairs, the author currently uses only the fronto parieto-occipital flap (Galvao) for total reconstruction, and the fronto-temporal flap (Schmid-Meyer), as well as the complex frontal island flap with the supratrochlear artery as pedicle for partial repairs. The author has abandoned several other techniques. The principle of the two last techniques consists in the preformation of the apico-columello-alar structure with the appropriate skin and cartilage grafts already in the donor area. For the correction of secondary stenoses, the author occassionally uses composite grafts from the interior aspect of the auricular crus helicis. PMID- 1456715 TI - [Repair techniques in perforations of the nasal septum]. AB - According to my experience extending over more than 20 years (more than 100 cases) in the treatment of septal perforations, I have the deep conviction that all techniques using local flaps should actually be considered to be obsolete, as the blood supply is insufficient. Perforations with diameter up to 4 cm can be closed in a one stage procedure with extensive dissection of the muco perichondrium and mucoperiosteum of the septum, the vault and the vestibular and cavity floor. The hole in the quadrangular plate can be reduced by a push back or push down manoeuver of part of the cartilage. For closure of perforations larger than 4 cm in diameter, I use a 2-3 stage procedure using a composite buccal flap with three layers (mucosa-cartilage and mucosa) and a gingivo-labial pedicle. Thus all kinds and sizes of perforations can be closed surgically avoiding the use of silicone obturators which only enlarge the hole. PMID- 1456716 TI - [Value of interrupted resection of the lateral crus in surgery of the nasal tip]. AB - Three goals have to be achieved in the surgery of the tip of the nose. Separately or joined together, they contribute to modify the height, rotation or width of the tip. Interrupting resection of the upper legs gives the ability to modify both the projection and the rotation of the tip. The authors present this technique, emphasizing the precise location of the knee of the upper legs and the interest to perform interrupting resections laterally to this region. PMID- 1456717 TI - [Esthetic pinching of the globular nasal tip. Technical note]. AB - A conservative technique designed to simple reduce the width of nasal tip is presented. It consists of approximation of the anterosuperior segments of alar lateral crus after their elevation on median pedicles. A marginal inferior band of alar cartilage is left adherent to the nasal mucosa. The procedure is completed without cartilaginous excision. We tried this technique in ten rhinoplasties and the results were satisfactory. The nasal tip narrowing obtained has no significant effect on either tip projection and position or nostril shape. PMID- 1456718 TI - [Treatment of cleft lip and palate: long-term results]. AB - Since 1958, 900 children with cleft lip and palate were operated on at the University Hospital Brugmann in Brussels. Until 1981, the children were operated at 6 months for the lip and at 18 months for the palate with two flap palatoplasties. Since 1982, R. Malek's technique and sequence were adopted. The results after 5 years follow-up are analyzed between two groups of 50 and 49 children operated with the two techniques. Growth of the maxillary arch and phonation are well improved in the second group, but no improvement was observed in terms of hearing. PMID- 1456719 TI - [Partial anterior chondrotomy in the correction of prominent ears. Apropos of 140 re-examined cases]. AB - 336 patients have been operated for protruding ears. 140 of them have a long term postoperative follow-up. The anterior partial chondrotomies are opposed to the other surgical procedures and give the opportunity for a comparative and retrospective study. Surgical indications and procedures, use of antibiotics, postoperative follow-up, and complications are studied. 95% of results are good or very good whatever the surgical procedure. The authors remain the posterior and anterior access for partial chondrotomy. PMID- 1456720 TI - [Evaluation of the Mustarde technique in the treatment of prominent ears. Apropos of 1100 patients]. AB - The analysis of a homogenous series of 1,100 patients with prominent ears confirmed the reliability of the Mustarde technique and the reversibility of the iatrogenic deformities related to this procedure. PMID- 1456721 TI - [Cutaneous retraction. Data from liposuction and other clinical procedures]. AB - The remarkable capacity of the skin to stretch is used in the skin expander technique. In parallel, the skin is also able to retract, which is very useful for the plastic surgeon. This ability to retract may open the road for new techniques. Suction lipectomy, which allows removal of large volumes of fat without skin resection, is a privileged technique for the study of retractability characteristics. This study compares the pre and postoperative conditions in 392 cases of body liposuction and 108 cases of cervicofacial liposuctions, to determine the factors which influence skin retraction. It appears that age and the total amount of fat removed have an incidence on the time needed to obtain the final result. However the treatment site emerges as a determinant factor on the potential of the skin to retract postoperatively. In practice, the skin elasticity appears to be very different in different treatment sites, and considerable variations can even be observed between two neighbouring regions. In the neck and cheeks the skin seems considerably more retractable than in other sites, and we can trace the boundaries of the optimal retractability for the liposuction: "the golden triangle at the neck". The considerable plasticity of the skin overlying the neck contrasts with the poor ability of facial skin to retract. On the body, the skin resumes its previous form in the vast majority of patients (90%). These data, derived from a liposuction study, may be compared with other clinical observations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456722 TI - [Keloid cicatrix of the face and neck. Apropos of 81 cases treated in Dakar]. AB - The authors report their experience of the treatment of 81 cases of keloid scars in Africa. Many methods have been proposed and used but they do not consistently lead to good results. The fact that many operations have been indicates their back of efficacy. The natural tendency towards recurrence dictates the correct choice of operation. The best result is obtained by combining surgery with radiotherapy. PMID- 1456723 TI - ["Pseudo-kite" flap of the index finger with LLL-plasty in the reconstruction of the first commissure]. AB - The authors describe a peninsular diamond-shaped flap raised from the dorsolateral surface of the index finger to cover a defect of the first web space. The donor site is covered by an "LLL" Dufourmentel flap tailored on the dorsum of the hand avoiding a skin graft on the exposed surface of the hand. PMID- 1456724 TI - [Radial forearm free flap with double skin island. Apropos of a clinical case]. AB - The authors report a case of double island forearm flap for a double defect on the inferior part of the leg. The chinese flap is the only flap which has a segmental and staged vascularisation allowing multiple island skin flaps to be performed separated only by the vascular pedicle. PMID- 1456725 TI - [Microsurgical repair after excision of large cancers. Apropos of 14 cases]. AB - The specialty which has benefited the most from the rapid development of reconstructive microsurgery over the last decade, has been plastic surgery. In particular, the authors refer to reconstructive microsurgery after malignant tumor resection. Resections which used to cause serious psychological problems or which required multiple reconstructive procedures, can now be performed as a single stage procedure with good oncological, functional and aesthetic results. This experience concerns the treatment of 14 primary or recurrent malignant tumors of the skin and soft tissues using microsurgical techniques. The free latissimus dorsi musculocutaneous flap was the flap most commonly used. The authors also used the groin flap, the scapular flap, the tensor fasciae latae flap, the dorsalis pedis flap and finally the jejunum combined with the second metatarsus to reconstruct the mandible and the floor of the mouth. Complications consisted of complete necrosis of a dorsalis pedis flap and two revisions were performed for venous thrombosis. With a minimum follow-up of 5 years, one patient has developed a local recurrence and another has developed regional lymph node metastases. The functional and aesthetic results were quite satisfactory. The authors believe that microsurgery is a very valuable technique to treat difficult reconstructive problems. PMID- 1456726 TI - [Breast ptosis. Classification and summary of surgical indications]. AB - A general classification of ptotic breasts is proposed by the author in four main groups. 1) Precocious ptotic breasts including ptosis because of anomalies of skin elasticity and primary morphological ptotic aspects of the breast. 2) Ptotic breast as a result of excess of volume due to early hyperplasia, because of excess weight (around puberty, around pregnancy, around menopause). 3) Acquired ptotic small or long breast by fibrous retraction, or after weight loss. 4) Asymmetric ptotic breast, either primary, presenting at puberty or secondary presenting around pregnancy or after weight variations, or iatrogenic. An approach to the morphological analysis of each type of ptosis includes evaluation of skin quality, glandular density, relation between both. The role of weight stability is also discussed before a brief summary of the author's choice of techniques. PMID- 1456727 TI - [Controversy about prostheses: a false problem?]. PMID- 1456728 TI - Thrombocytopenia in a retrovirally-induced murine erythroleukemia. AB - A variant strain of Rauscher leukemia virus (RLV-A) obtained from a transplantable murine monomyelocytic leukemia causes a disease characterized by frank anemia, wasting, hepatosplenomegaly and erythroblastosis. The involvement of platelets in this disease are reported here. The RLV-A induced a severe thrombocytopenia (25 percent of control level) at the terminal stage of disease. This thrombocytopenia was not associated with disseminated intravascular coagulopathy since the prothrombin times were always within normal limits. The partial thromboplastin time was elevated in the terminal stages of disease and was found to be associated with factor deficiencies, possibly owing to the presence of anti-factor antibodies, in the intrinsic coagulation pathway, especially factor VIII. Further, splenectomy did not abolish the thrombocytopenia, since splenectomized, virally infected animals also developed severe thrombocytopenia (29 percent of control levels). The ensuing splenomegaly during progression of disease was not the cause of the thrombocytopenia. A physiological response to the severe thrombocytopenia was the production of larger size platelets. At terminal stages of the disease, platelet volume increased to 4.2 mu 3 (normal is 3.0 mu 3). An increase in platelet volume was also observed in splenectomized, virally infected animals. Electron microscopy indicated that these circulating platelets contained c-type viral particles. Viral infection was associated with decreased life span of circulating platelets, as measured by 75Se-methionine at mid and terminal stages of the disease. Our results suggest that direct viral infection of platelets and/or megakaryocytes with subsequent cell lysis is a possible cause of the observed thrombocytopenia observed in RLVA-induced disease and may also occur in other retrovirally-induced diseases. PMID- 1456729 TI - Clinical applications of capillary electrophoresis. AB - Capillary electrophoresis (CE) is a new powerful separation technique that often exhibits higher resolution and shorter analysis times than high performance liquid chromatography (HPLC) or agarose electrophoresis (AE). The separation can be accomplished based on charge as well as on size, hydrophobicity, and stereospecificity. In addition to high resolution, the most significant features of CE are ease of use, low cost of operation, and the speed of the analysis thus suitable for stat work. Examples of the application of CE in the field of clinical diagnosis which are discussed include: therapeutic drug monitoring, proteins (serum, urinary and cerebrospinal fluid), and hemoglobins. This technique can reveal compounds which are not routinely analyzed in the lab thus opening a new area for the clinical investigator. PMID- 1456730 TI - Assessment of mitochondrial function in cells grown in tissue culture. AB - To assess mitochondrial function (pyruvate dehydrogenase [PDH] activity), cells were grown in the appropriate media to confluence, rinsed and incubated in glucose free media containing 25 microM L-lactate and [1-14C]-D,L-lactate. Lactate oxidation was measured as the amount of lactate oxidized in nmol of 14CO2 generated per mg of protein per minute. Basal activity varied with cell number and the cell type studied: fibroblast 2.26 +/- 0.01; Chinese hamster ovary (CHO) 42 +/- 0.4; BC3H-1 52 +/- 2.1 nmol per mg per minute. The CHO cells screened for PDH activity decreased their dependence on lactate as a substrate in the presence of 5mM glucose by 60 percent. Increasing the cold lactate concentration diluted the labelled lactate available for pyruvate oxidation in a dose dependent manner. The mitochondrial inhibitor rotenone (25 microM) decreased assay activity by > 75 percent in CHO and BC3H-1 cells. The lactate oxidation assay was shown to be sensitive enough to measure insulin stimulation of PDH in a dose dependent manner with maximum activity occurring at concentrations between 1 microU per ml and 100 microU per ml. PMID- 1456731 TI - Hemoglobin C--G-Georgia double heterozygosity: a case report. AB - A 12-month-old black female with an unremarkable past medical history was admitted to the hospital with respiratory distress and fever without identified sepsis. Despite mechanical ventilation, the patient died as a result of respiratory insufficiency secondary to severe necrotizing bronchitis and bronchiolitis with pneumonia. Electrophoretic and biochemical analyses of the patient's hemoglobin showed the patient to be a double heterozygote for hemoglobin C (a beta chain variant) and hemoglobin G-Georgia (an alpha chain variant). This is the first report of this combination of hemoglobin variants. PMID- 1456732 TI - The effect of metal chelators on lipid peroxidation in irradiated erythrocytes. AB - Prophylactic irradiation of blood and blood components is accepted practice in order to prevent graft-versus-host disease from infused lymphocytes. Irradiation, however, results in increased red cell potassium (K+) loss, along with other possible effects that may affect red cell function and viability. Lipid peroxidation (LP), a process initiated by the production of oxygen free radicals, is increased in red cells in the presence of reactive iron species and various heme moieties. In this report, it is noted that not only is plasma K+ significantly increased following blood irradiation, but LP is also increased compared with paired non-irradiated blood samples. Furthermore, various metal chelators significantly reduce LP in the irradiated samples. These chelators also significantly reduced the rate of cellular K+ loss during the four day 37 degrees C incubation period. This study further suggests that the addition of selected metal chelators may be effective in both irradiated and non-irradiated stored blood by improving the function and viability of transfused erythrocytes. PMID- 1456733 TI - Patterns of reactivity of human anti-GM1 antibodies with spinal cord and motor neurons. AB - Human anti-GM1 antibodies from patients with lower motor neuron disease or predominantly motor neuropathy recognize carbohydrate determinants shared by GM1 and related glycolipids and glycoproteins, but the identity of the antigens to which they bind in tissue is unknown. We examined the binding of anti-GM1 antibodies with differing fine specificities to spinal cord, isolated motor neurons, and dorsal root ganglia neurons in order to characterize the tissue antigens. All anti-GM1 antibodies tested bound to the surface of bovine spinal motor neurons and immunostained the gray matter of unfixed sections of spinal cord. The staining was blocked by cholera toxin, which is specific for GM1, indicating that GM1 itself was the target antigen. Binding to white matter was more variable and depended on fixation and the fine specificities of the antibodies. The anti-GM1 antibodies did not bind to dorsal root ganglia neurons in tissue sections or in culture. These studies suggest that the autoantibodies might exert their effect, in part, by binding to GM1 on the surface of motor neurons, and that the absence of binding to dorsal root ganglia neurons might explain the lack of sensory abnormalities in affected patients. PMID- 1456734 TI - Hemifacial spasm: evaluation by magnetic resonance imaging and magnetic resonance tomographic angiography. AB - We evaluated 37 patients with hemifacial spasm and 16 age-matched control patients with other neurological disorders using magnetic resonance (MR) imaging, MR angiography, and MR tomographic angiography. MR tomographic angiography is a new technique using computer reconstruction of MR angiographic images to create coronal angiotomes that display tissue and arterial structures on the same image. Twenty-four of 37 (64.9%) patients with hemifacial spasm had ipsilateral vascular compression of cranial nerve VII or the pons noted by this technique, whereas only 1 of 16 (6.3%) control patients had compression. MR imaging and MR angiography were less sensitive and less specific in evaluating for vascular compression. This study supports vascular compression of cranial nerve VII or the pons as a cause of hemifacial spasm, and demonstrates MR tomographic angiography's value as an excellent, noninvasive technique to demonstrate the compression. PMID- 1456735 TI - Magnetic resonance: a noninvasive approach to metabolism, circulation, and morphology in human brain death. AB - Phosphorus (31P) magnetic resonance spectroscopy and magnetic resonance imaging were used to study the intracellular metabolism, circulation, and morphology in the brains of 3 patients with clinical brain death syndrome due to traumatic brain damage, subarachnoid hemorrhage, and acute occlusive hydrocephalus caused by a colloid cyst. Magnetic resonance spectra were characterized by a complete absence of ATP and were dominated by an intense inorganic phosphate signal. Magnetic resonance imaging revealed a uniform pattern of diffuse brain swelling and tentorial and foraminal herniation. Intracranial blood flow was absent on the magnetic resonance angiography projections. These preliminary findings suggest an important impact of magnetic resonance in the determination of human brain death. PMID- 1456736 TI - Ipsilateral fast corticospinal pathways do not account for recovery in stroke. AB - We tested the hypothesis that in adult humans, recovery from stroke results from the emergence of ipsilateral, fast-conducting corticospinal pathways. In 10 patients recovering from stroke, the unaffected hemisphere was stimulated with an electromagnet and changes in the firing probability of single biceps motor units were used to derive postsynaptic potentials in single biceps motoneurons. Stimuli sufficient to excite the neurons of the fast-conducting corticospinal pathway (as shown by short-latency facilitation of contralateral biceps motoneurons) did not produce short-latency depolarization of ipsilateral biceps motoneurons. The hypothesis is therefore not supported. PMID- 1456737 TI - Skeletal muscle toxoplasmosis in patients with acquired immunodeficiency syndrome: a clinical and pathological study. AB - The present article describes the clinical and pathological findings in 5 human immunodeficiency virus (HIV)-infected patients with muscle toxoplasmosis. The patients had marked lymphopenia (5/5), with less than five CD4+ cells/mm3 (3/3), when they developed fever (5/5), and multiorgan failure (5/5), including diffuse encephalitis, pneumonia, pancytopenia, and myopathy. Muscle involvement included weakness and wasting (4/5), myalgias (3/5), and high serum creatine kinase levels (3/3). Serology for toxoplasmosis showed high IgG titers in 3 patients (3/4). Anti-Toxoplasma therapy resulted in complete recovery in 2 patients. Muscle toxoplasmosis was detected by biopsy (3/5) or postmortem evaluation (2/5), and was identified using immunocytochemistry and electron microscopy. Toxoplasma cysts were detected in 0.5 to 4% of muscle fibers close to or remote from necrotic fibers and inflammatory infiltrates. Muscle fibers strongly expressed the major histocompatibility complex class I antigen (2/2) as in polymyositis. We suggest that Toxoplasma gondii should be sought by muscle biopsy in patients who have acquired immunodeficiency syndrome with fever, encephalitis, multiorgan dysfunction, and elevated serum creatine kinase levels of obscure origin. PMID- 1456738 TI - Calbindin-D28k in the basal ganglia of patients with parkinsonism. AB - An immunohistochemical study was carried out to investigate the topographic distribution of calbindin-D28k in the human basal ganglia and substantia nigra and its alterations in patients with idiopathic Parkinson's disease (PD), parkinsonism-dementia complex on Guam, progressive supranuclear palsy, and striatonigral degeneration. In normal control subjects, calbindin-D28k immunoreactivity was identified in the medium-sized neurons and neuropil of the matrix compartment of the striatum, the woolly fiber arrangements of the globus pallidus, and the fiber structures of the pars reticulata of the substantia nigra. Calbindin-D28k expression in the basal ganglia of patients with PD and parkinsonism-dementia on Guam was not different from that of control subjects, suggesting that the matrical output pathway is spared in these disorders. In contrast, its disruption is inferred from the observed disorganization of woolly fibers in the globus pallidus of patients with progressive supranuclear palsy and the reduced calbindin-D28k reactivity in the putaminal matrix and the pars reticulata of the substantia nigra of subjects with striatal degeneration. Thus, our results indicate that calbindin-D28k is a useful marker for the projection system from the matrix compartment and that its expression is modified in patients with progressive supranuclear palsy and striatal degeneration. PMID- 1456739 TI - Three- and four-year cognitive outcome in children with noncortical brain tumors treated with whole-brain radiotherapy. AB - Cognitive function and school achievement were studied prospectively over 3 to 4 years in 19 children treated for brain tumors with whole-brain radiotherapy; 14 of 19 also received adjuvant chemotherapy. For the group as a whole, mean IQ fell from a baseline of 104 to 92 at follow-up (p < 0.01). Age was inversely correlated with change in IQ over time (r = 0.71; p < 0.001). Children younger than 7 years at diagnosis had a mean IQ loss of 27 points, while children over 7 years at diagnosis showed no significant decrease in IQ. Decline in IQ occurred between baseline and year 2 of follow-up; none could be documented between years 2 and 4. All children younger than 7 years at diagnosis were receiving special education at follow-up; 50% of the children over 7 years at diagnosis were receiving supplemental educational services. PMID- 1456740 TI - Amygdala cell loss and atrophy in Alzheimer's disease. AB - The amygdala and its subnuclei undergo severe volumetric atrophy in Alzheimer's disease (AD). To determine whether this atrophy is due to loss of neuropil, specific neuronal populations, or both, we evaluated the number, size, and packing density of neurons and glia in the cortical and magnocellular basal amygdaloid subregions. The neuropil fraction did not change with AD in either region. Despite a mean 35% increase in cell packing density in the AD amygdala, total numbers of neurons and glia within tissue sections were reduced significantly; medium and large neurons were preferentially affected. The total number of small neurons was stable in the AD sample despite sharp reductions in nuclear size, suggesting that AD also results in pronounced amygdaloid neuronal shrinkage. Differences in the degree of cell loss between the two nuclei as well as changes in glial cell numbers are discussed in relation to characteristic AD neuropathology and relevant anatomical connectivity. PMID- 1456741 TI - Neurological intensive care. AB - Neurological intensive care has evolved from the principles of respiratory care established during the poliomyelitis epidemics into a broad field encompassing all of the acute and serious aspects of neurological disease. The economic and political complexities of modern intensive care play a major role in organizing a unit and building a program. Central themes of practice in modern neurological intensive care units include the clinical physiology of intracranial pressure, cerebral blood flow, and brain electrical activity; the systemic abnormalities and medical complications of nervous system diseases; postoperative care; and management of neuromuscular respiratory failure. Treatment of severe stroke and cerebral hemorrhage, brain death, ethical dilemmas of severe neurological illnesses, and the neurological features of critically ill medical patients are also becoming neurological intensive care pursuits. The "neuro-intensivist" is trained to defragment medical care by combining knowledge of neurological diseases with the techniques of intensive care. Future directions include the clinical implementation of brain resuscitation and brain-sparing therapies, sophisticated monitoring of electrophysiological and intracranial physiological indices, and further understanding of the dysfunction of other organs that follows brain and nerve failure. PMID- 1456743 TI - Familial adult-onset muscular dystrophy with leukoencephalopathy. AB - We report on 3 siblings with an adult-onset, predominantly distal muscle weakness. In the female index patient this was associated with epilepsy and a progressive spastic ataxic gait, while the 2 other siblings had no appreciable clinical nervous system involvement. Additional investigations revealed muscular dystrophy and leukoencephalopathy in all 3 siblings. We conclude that this familial adult-onset muscular dystrophy associated with leukoencephalopathy represents a newly recognized autosomal recessive syndrome. PMID- 1456742 TI - The persistent vegetative state in children: report of the Child Neurology Society Ethics Committee. AB - Increasing concern about children in a persistent vegetative state (PVS) prompted a survey of members of the Child Neurology Society regarding aspects of the diagnosis and management of this disorder. Major findings of those responding to this survey (26% response rate) were as follows: (1) 93% believed that a diagnosis of PVS can be made in children, but only 16% believed that this applied to infants younger than 2 months and 70% in the 2-month to 2-year group; (2) a period of 3 to 6 months was believed to be the minimum observation period required before a diagnosis of PVS could be made; (3) 86% believed that the age of the patient would affect the duration of time needed to make the diagnosis of PVS; (4) 78% thought a diagnosis of PVS could be made in children with severe congenital brain malformations; (5) 75% believed that neurodiagnostic studies would be of value and supportive of the clinical diagnosis of PVS; (6) members' opinions as to the average life expectancy (in years) for the following age groups after the patients were considered vegetative were: newborn to 2 months, 4.1; 2 months to 2 years, 5.5; 2 to 7 years, 7.3; and more than 7 years, 7.4; (7) 20% believed that infants and children in a PVS experience pain and suffering; and (8) 75% "never" withhold fluid and nutrition from infants and children in a PVS and 28% "always" give medication for pain and suffering.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456744 TI - Isolated granulomatous angiitis of the spinal cord. AB - We describe a 31-year-old diabetic man, with granulomatous angiitis confined to the spinal cord, who developed rapidly progressive spastic paraplegia, clinically interpreted as being secondary to a spinal cord infarct. At the time of autopsy, vasculitis was limited to the spinal cord, without involvement of cerebral vessels. The inflammatory cells were predominantly CD4+ T lymphocytes, with few CD8+ T and B lymphocytes. The phenotypical composition of the inflammatory infiltrate is similar to that described in other granulomatous disorders such as sarcoidosis and tuberculin reaction. PMID- 1456745 TI - Carnitine acetyltransferase activity in the human brain and its microvessels is decreased in Alzheimer's disease. AB - L-Carnitine and acetyl-L-carnitine facilitate mitochondrial beta-oxidation of fatty acids. In the brain, they may also have a role in acetylcholine synthesis. Carnitine acetyltransferase catalyzes the interchange between L-carnitine and acetyl-L-carnitine. Recently, acetyl-L-carnitine was reported to have a beneficial effect in patients with Alzheimer's disease. We therefore assessed carnitine acetyl-transferase activity in selected brain regions and in isolated cerebral microvessels obtained at autopsy from patients with Alzheimer's disease and from age-matched control subjects. We found a 25 to 40% decrease in carnitine acetyltransferase activity in patients with Alzheimer's disease, which attained statistical significance in most brain regions and in cerebral microvessels. These findings document another neurochemical abnormality in patients with Alzheimer's disease and provide a rationale for the use of acetyl-L-carnitine in the treatment of patients with Alzheimer's disease. PMID- 1456746 TI - Extraocular muscles are spared in advanced Duchenne dystrophy. AB - Fast-twitch extremity muscle fibers are preferentially affected in Duchenne's and Becker's muscular dystrophy. Since saccades are thought to be mediated by fast twitch fibers, saccadic velocities would be expected to be decreased in these patients. Using infrared oculography, we found that the peak velocities of saccades in 3 patients with advanced Duchenne's or Becker's muscular dystrophy were normal. Clinical findings in 7 other patients with these forms of dystrophy were normal. This investigation is the first study of ocular motility in Duchenne's and Becker's muscular dystrophy. It demonstrates that extraocular muscle function is preserved and suggests that fast-twitch fibers in extraocular muscles possess properties that protect against degeneration. PMID- 1456747 TI - Alpha-tocopherol levels in brain are not altered in Parkinson's disease. AB - alpha-Tocopherol (vitamin E) levels in normal brain were lower in the cerebellum than in the cerebral cortex or basal ganglia. There was no difference in alpha tocopherol levels in the cerebellum, basal ganglia, or cerebral cortex between control subjects and patients with Parkinson's disease. PMID- 1456748 TI - Francis X. Dercum. PMID- 1456749 TI - Inheritance of tomaculous neuropathy. PMID- 1456750 TI - Causes of stroke. PMID- 1456751 TI - Mitochondrial DNA mutation and Leigh's syndrome. PMID- 1456752 TI - Photodynamic therapy for the treatment of basal cell carcinoma. AB - BACKGROUND: Photodynamic therapy is an investigational method for the treatment of a variety of solid tumors. The purpose of this study was to determine the optimum factors and illustrate the effectiveness of photodynamic therapy in the treatment of basal cell carcinomas. This was a prospective study in which patients presenting with primary or recurrent basal cell tumors, particularly but not exclusively widespread tumors or large single tumors, were offered the option of photodynamic therapy in their treatment regimen. RESULTS: Patients were administered 1 mg/kg of a photosensitizer (Photofrin II). Light doses (630 nm) ranged from 72 to 288 J/cm2. A total of 37 patients with 151 sites were treated in this study. A complete response rate of 88% was achieved with one application. Morbidity was low; the most significant side effects were moderate pain and edema. CONCLUSIONS: Photodynamic therapy is a modality that offers localized treatment of primary or recurrent nonmelanoma skin cancer. By applying reciprocal doses of photosensitizer and light, the efficacy of photodynamic therapy in the treatment of skin lesions is demonstrated achieving significant light penetration into tissue with a high complete response rate of the lesions and acceptable normal tissue response. PMID- 1456753 TI - Frequency and prognostic significance of clonal T-cell receptor beta-gene rearrangements in the peripheral blood of patients with mycosis fungoides. AB - BACKGROUND: Previous studies have shown that peripheral blood involvement is a poor prognostic sign in patients with cutaneous T-cell lymphoma. However, evaluation of the results of these studies is difficult. In this study peripheral blood mononuclear cells from 45 patients with various stages of mycosis fungoides (MF) were investigated for the presence of clonal T-cell populations by T-cell receptor beta (TCR beta)-gene rearrangement analysis. RESULTS: Clonal TCR beta gene rearrangements were found in five (11%) of 45 patients with MF, including one (3%) of 31 patients without MF and four (27%) of 15 patients with histologically confirmed lymph node involvement. With respect to skin stage, clonal T-cell populations were detected in one (4%) of 23 patients with plaque stage disease, two (10%) of 19 patients with tumor stage disease, and two (50%) of four patients with erythrodermic MF. In the group of patients with lymph node involvement the median survival of patients with detectable clonal T-cell rearrangements in the peripheral blood was much shorter (3 months) than that of patients without clonal rearrangements (16 months). CONCLUSIONS: The results of this study indicate that clonal TCR beta-gene rearrangements, as detected by Southern blot analysis, are uncommon in the peripheral blood of patients with MF, in particular in patients without histologically documented lymph node involvement. The presence of clonal T-cell populations in the peripheral blood of MF patients with lymph node involvement is usually associated with rapidly fatal disease. PMID- 1456754 TI - The incidence and prevalence of dermatitis herpetiformis in Utah. AB - BACKGROUND AND DESIGN: The incidence and prevalence of dermatitis herpetiformis has never been formally evaluated in any area of the United States. Several northern European studies have shown prevalence rates ranging from 1.2 per 100,000 to 39.2 per 100,000. The present study was performed to evaluate the incidence and prevalence of dermatitis herpetiformis in Utah. Information from 240 patients diagnosed with dermatitis herpetiformis was compiled from hospital records throughout Utah, as well as the sole private dermatopathologist in the state, and from the university referral center of the state. Criteria for inclusion in the study were a clinical diagnosis of dermatitis herpetiformis plus granular deposition of IgA in dermal papillae by direct immunofluorescence of uninvolved skin, or histopathologic findings consistent with the disease. Clinical diagnosis and response to dapsone alone was considered insufficient for inclusion in the study. On the basis of these criteria, as well as exclusion of non-Utah residents, 188 of the original 240 patients qualified for the study. RESULTS: The prevalence of dermatitis herpetiformis in Utah in 1987 was 11.2 per 100,000. The mean incidence for the years 1978 through 1987 was 0.98 per 100,000 per year. The mean age at onset of symptoms for male patients was 40.1 years, and that for female patients was 36.2 years. The male-female ratio was 1.44:1. CONCLUSIONS: This represents the first evaluation of the incidence and prevalence of dermatitis herpetiformis in the United States. These results are similar to those of the previous studies, probably because of Utah's largely northern European ancestry. This population base, plus a much smaller than average black and Oriental population, is likely to have produced a higher incidence and prevalence in Utah than would be seen in other areas of the United States. PMID- 1456755 TI - Pyoderma faciale. A review and report of 20 additional cases: is it rosacea? AB - BACKGROUND AND DESIGN: Pyoderma faciale was originally described by O'Leary and Kierland in 1940. It is characterized by the sudden onset of monstrous coalescent nodules and confluent draining sinuses confined to the face of young women in their early 20s. This report summarizes our results in 20 cases. The women were 15 to 46 years old (mean, 25 years). RESULTS: All women were flushers and blushers. Histopathologic examination revealed a dense perivascular and periadnexial infiltrate, including granulocytes, eosinophils with epithelioid granulomas, and septal and lobular panniculitis. No consistent laboratory abnormalities were found. After much therapeutic experimentation, we developed an effective treatment plan, based on a combination of oral isotretinoin and corticosteroids. CONCLUSION: We regard it as an extreme form of rosacea and suggest it be renamed rosacea fulminans in analogy with its counterpart, acne fulminans. PMID- 1456756 TI - Q-switched ruby laser therapy of nevus of Ota. AB - BACKGROUND: The Q-switched ruby laser has been demonstrated to provide selective photothermolysis of pigmented tissue at a wavelength of 694 nm and a pulse width of 40 ns with dermal penetration. It was used to treat 15 patients with nevus of Ota involving the face with an age range of 6 to 52 years. Other methods of treatment for the nevus of Ota have either left scarring or were ineffective. The clinical efficacy of this laser treatment was evaluated in a comparative photographic analysis. OBSERVATIONS: Complete clearing was noted in four of the 15 patients and a minimum of 50% lightening of the original color in the remaining 11. Ten of the 15 patients were Asian, two were white, two were Hispanic, and one was Indian. The energy fluence used varied between 6 and 10 J/cm2, and the number of treatments ranged from 1 to 7. Significant lightening or clearing was found at the higher energy ranges of 9 to 10 J/cm2 with significantly less lightening noted at the lower energy range of 6 to 8.5 J/cm2. No scarring was noted in any of the 15 patients, and some isolated hypopigmentation was noted in one of the subjects. Transient postinflammatory hyperpigmentation of 2 months' duration was noted in only one patient. CONCLUSION: Q-switched ruby selective photothermolysis appears to be an effective and safe method of lightening or removing nevus of Ota. PMID- 1456757 TI - Pharmacologic treatment of severe skin-picking behaviors in Prader-Willi syndrome. Two case reports. AB - BACKGROUND: Prader-Willi syndrome (PWS) is characterized by hypotonia at birth, hypogonadism, early childhood obesity, and mental deficiency. Other behavioral symptoms that become prominent during adolescence and adulthood include temper outbursts, stealing and hoarding food, and skin picking. The self-excoriating skin picking behavior observed in individuals with PWS is quite common and can lead to persistent sores and infections, even requiring hospitalization. OBSERVATION: Two patients with PWS who displayed repetitive, self-mutilatory behavior of skin picking are described. They were both treated successfully with different doses of fluoxetine, a selective serotonin reuptake inhibitor. CONCLUSIONS: The skin-picking behavior in patients with PWS may be a variant of the spectrum of obsessive-compulsive disorders. Obsessive-compulsive disorders have been successfully treated with serotonin reuptake inhibitors such as fluoxetine. Thus, fluoxetine may be considered an option in the management of skin-picking behavior in patients with PWS. PMID- 1456758 TI - Treatment of pemphigus vulgaris with pulse intravenous cyclophosphamide. AB - BACKGROUND: Although corticosteroids have dramatically altered the prognosis in pemphigus vulgaris, morbidity and mortality from systemic corticosteroid side effects remains high. While immunosuppressive agents have been successfully used in pemphigus vulgaris, there is a high incidence of side effects with these agents as well. Particularly bothersome are reports of increased risk of malignancy with long-term use of immunosuppressive agents. For these reasons, we used a protocol that includes low-dose oral cyclophosphamide coupled with pulse intravenous cyclophosphamide in two patients with recalcitrant pemphigus vulgaris. OBSERVATIONS: Both patients responded well to monthly doses of intravenous cyclophosphamide with rapid decrease in the frequency and severity of blistering, resulting in resolution of their disease after 7 and 10 months, respectively. CONCLUSIONS: Pulse doses of immunosuppressive agents appear to be successful in the treatment of pemphigus vulgaris. High-dose steroid therapy can be tapered with the use of this treatment. Because monthly intravenous doses of cyclophosphamide lead to a substantially reduced cumulative dose, when compared with standard oral regimens, the risk of developing malignancy may also be reduced. Further studies using larger groups of patients are needed to evaluate the efficacy of pulse intravenous cyclophosphamide in pemphigus vulgaris. Long term follow up will be necessary to compare the incidence of malignancy in patients receiving pulse doses of immunosuppressive agents with that in patients receiving continuous oral treatment. PMID- 1456759 TI - Photodynamic therapy in dermatology. Shedding a different light on skin disease. PMID- 1456760 TI - Multiple ulcers in an elderly man. Necrotizing erythema nodosum leprosum (ENL) (necrotizing ENL). PMID- 1456761 TI - Erythematous plaque on the leg. Vilanova's disease (subacute nodular migratory panniculitis). PMID- 1456762 TI - Scars on the legs. Cutaneous fibrosis resulting from intracutaneous injection of cocaine. PMID- 1456763 TI - Cyclic fever and rash in a 66-year-old woman. Chronic meningococcemia. PMID- 1456764 TI - Photopheresis and systemic sclerosis. PMID- 1456765 TI - The significance of linear IgM deposits in the basement membrane zone. PMID- 1456766 TI - Erythromelalgia as a form of neuropathy. PMID- 1456767 TI - Multiple exostoses syndrome presenting as nail malalignment and longitudinal dystrophy of fingers. PMID- 1456768 TI - Extracorporeal photochemotherapy as adjunctive treatment in juvenile dermatomyositis: a case report. PMID- 1456769 TI - Photodistributed hereditary ochronosis. PMID- 1456770 TI - Treatment of oral hairy leukoplakia with podophyllin. PMID- 1456771 TI - Allergic contact dermatitis to white pine sawdust. PMID- 1456772 TI - Field evaluation of coverall fabrics: heat stress and pesticide penetration. AB - The effect of wearing coveralls on the heat stress of ten professional airblast applicators of ethion to Florida citrus were studied. During the period June 21, 1988 to August 9, 1988, applicators wore protective clothing of the same design, but made of seven different fabrics. Heat stress was evaluated by measuring the mean skin temperature, oral temperature, and heart rate of pesticide applicators. Subjects also provided subjective evaluations. Seven environmental variables were also monitored. Although each fabric was replicated an average of 17 times for thermal comfort and an average of 23 times for penetration, statistical tests for differences among fabrics were usually not significant at the p less than 0.05 level. Observed differences among suits were statistically significant at p = 0.27 for the heat stress experiment, and extended over the range p = 0.003-0.500 for the penetration experiment. Lighter weight, untreated fabrics marginally ameliorated heat stress under severe environmental conditions, but they allowed more pesticide penetration. PMID- 1456773 TI - Small area pesticides data: multiplicity and variability of pesticide usage on southern row crops. AB - Epidemiologic studies of possible effects of agricultural environments upon human health suffer from lack of reliable pesticides usage data. The Arkansas Reproductive Health Monitoring System has developed a method for estimating specific pesticides usage annually for sub-county regions, including amounts, application method, and months. This method is applied to 39 regions of 8 central Arkansas counties for 1980-82. The hugh variability of pesticides usage on individual crops demonstrates the inaccuracy likely if general survey estimates are employed. Annual usage of pesticides in a single sub-county region of 53,000 hectares (130,880 land acres) was greater than 1/2 million pounds (248,670 kg) of 60 pesticides, 40 of which were applied during a four month period. The multiplicity and variability of pesticides usage indicate the need for locally developed pesticides data for epidemiologic studies and for combined studies across regions with widely differing agricultural practices. PMID- 1456774 TI - Reproductive output of a meiobenthic copepod exposed to sediment-associated fenvalerate. AB - The benthic harpacticoid copepod, Amphiascus tenuiremis, was cultured through one generation at four concentrations (600, 300, 150, and 0 micrograms/kg) of sediment-associated fenvalerate, a synthetic pyrethroid insecticide, to assess effects on reproductive output and age structure. Two static renewal experiments with four replicates of each treatment were conducted. At the end of 21 days, surviving copepods were sorted and counted into adult males, adult females, copepodites, and nauplii. Fenvalerate was extracted from the sediment and measured by GC-MS. The number of individuals in each life-history stage in fenvalerate treatments was not significantly different from controls, except for increased adult females in fenvalerate in the second experiment. The overall lack of a fenvalerate toxic effect on A. tenuiremis was most likely because fenvalerate tightly binds to sediments and was probably not bioavailable to the copepods. Sediment-associated pesticides with large octanol:water partitioning coefficients (K(ow)'s) such as fenvalerate appear to be less toxic to infaunal copepods than those exhibiting smaller K(ow)'s. PMID- 1456775 TI - Effects of 2,4-dichlorophenoxyacetic acid on Rhizobium sp. membrane fluidity. AB - The effects of 1 mM 2,4-Dichlorophenoxyacetic acid on Rhizobium sp. in pure culture was studied. In a previous work it was demonstrated that this herbicide produces an alteration on the saturated to unsaturated phospholipid acyl chains ratio. In the present paper, it was found that this alteration produces a modification on the membrane fluidity in bacteria that had achieved the stationary phase. The same results were obtained when determinations were done in liposomes from sonicated lipids of treated bacteria, indicating that changes in phospholipid acyl chains may be the main cause of membrane fluidity alteration. In addition, it was determined that leucine transport as well as Ca(++)-ATPase activity (a membrane enzyme) was affected under the experimental conditions. PMID- 1456777 TI - Benzo(a)pyrene-blood protein adducts in wild woodchucks used as biological sentinels of environmental polycyclic aromatic hydrocarbons contamination. AB - Levels of benzo(a)pyrene-diolepoxide (BaPDE)-albumin and BaPDE-hemoglobin adducts in wild woodchucks (Marmota monax) have been measured to evaluate the potential usefulness of these parameters in the assessment of environmental contamination by polycyclic aromatic hydrocarbons (PAHs). Blood was obtained from nine woodchucks living near an aluminum electrolysis plant, contaminated area (Saguenay region, Quebec, Canada), and from eight living in a control area (Saint Roch-des-Aulnaies, Quebec, Canada). Blood samples were collected and plasma separated from red blood cells by centrifugation on site. Isolation of albumin (Alb) and hemoglobin (Hb) was performed in our laboratory and each protein fraction was subjected to mild acid hydrolysis yielding free benzo(a)pyrene (BaP) tetrol from the adducts. The analysis was performed by high performance liquid chromatography (HPLC) using fluorescence detection. For the control and contaminated areas geometric mean (interval) Alb adduct levels were 7.6 (0.8 29.3) and 69.6 (10.0-1,103) pmol tetrol/g protein (p less than 0.01) while the corresponding figures for Hb adduct levels were 0.40 (0.01-2.72) and 1.18 (0.02 12.8) pmol/g protein (p greater than 0.01). Alb but not Hb adduct levels were associated with the measured concentration of BaP in the vegetation samples collected on the site where each animal was found. This is compatible with the short half-life of Alb adducts and with the instantaneous image provided by BaP measurements in the collected vegetation samples. BaPDE-blood protein adducts measured in wild animals appear to be good biomarkers of environmental contamination by PAHs. PMID- 1456776 TI - Oxidative changes in brain of aniline-exposed rats. AB - Oxidative stress in rat cerebellum, cortex and brain stem after a short-term high dose exposure to aniline vapors under conditions akin to those after major chemical accidents, was studied. Significant increases in superoxide dismutase isozyme activities and formation of thiobarbituric acid reactive material along with depletion of ascorbic acid and non-protein sulfhydryl content suggest impairment of antioxidant defenses 24 h after single exposure to 15,302 ppm aniline vapors for 10 min. PMID- 1456778 TI - Early life stage survival of striped bass in the Delaware River, USA. AB - Four 96-h in situ bioassays were conducted on or near the striped bass spawning grounds in the Delaware River within the States of Delaware, New Jersey and Pennsylvania, USA during 1989 to determine if water quality was sufficient to support larval survival. Tests were accomplished by holding 500 striped bass yolk sac larvae in each of two 75 L chambers at four locations in the river ranging from north of Philadelphia, PA to Salem, NJ and at one location in the Chesapeake and Delaware Canal. Survival varied significantly among stations; highest survival was in the Chesapeake and Delaware Canal, where it averaged more than 50%. Lowest survival occurred at the station near Salem, NJ, approximately 30 km downriver of the primary spawning grounds, where less than 1% of the larvae survived in any of the tests. Survival at stations closest to the primary spawning grounds was weather-dependent; survival was over 47% during periods of little rainfall, but only 11% following periods of higher than average rainfall. PMID- 1456779 TI - Effects of acute and chronic acidification on three larval amphibians that breed in temporary ponds. AB - This study explored the effects of acute (7 days) and chronic (4 months) exposure to pH 4.2 on three species of larval amphibians, Ambystoma jeffersonianum, Ambystoma maculatum, and Rana sylvatica. Acute tests were conducted in 24 impermeable enclosures in three temporary ponds. Total dissolved aluminum was higher in acidified enclosures in comparison with controls (pH 4.2, [Al] approximately 10-30 microM and pH greater than 4.7, [Al] approximately 5-15 microM, respectively). Greater mortality of A. jeffersonianum occurred at pH 4.2 than at pH greater than 4.7, whereas survival of A. maculatum and R. sylvatica were unaffected by pH. Mean wet masses of R. sylvatica were significantly lower at pH 4.2 than at pH greater than 4.7, but mean wet masses of surviving A. jeffersonianum and A. maculatum were not influenced by pH. There were no pH related differences in body sodium concentration in larval R. sylvatica. Chronic acidification of mesocosms to pH 4.2 ([Al] approximately 16 microM) (controls = pH greater than 6, [Al] approximately 0.1 microM) resulted in total mortality of A. jeffersonianum. Survival of A. maculatum and R. sylvatica were not associated with pH, but survival of A. maculatum was low at both pH levels. Time to metamorphosis was longer for R. sylvatica maintained at pH 4.2, but not for A. maculatum. No differences in wet masses at metamorphosis were observed for R. sylvatica or A. maculatum. These results indicate that short and long term acidification of temporary wetlands could dramatically affect amphibians which rely upon them as breeding sites, either by causing mortality or by decreasing growth rates. PMID- 1456781 TI - Shell disease and metal content of blue crabs, Callinectes sapidus, from the Albemarle-Pamlico Estuarine System, North Carolina. AB - Concentrations of 13 elements were determined for three tissues (gill, hepatopancreas, muscle) in diseased crabs from a contaminated estuary (Pamlico River, NC), and in non-diseased crabs from both the contaminated estuary and a relatively uncontaminated area (Albemarle Sound, NC) during the fall 1989 and summer 1990. The diseased crabs had lesions which completely penetrated their dorsal integument, while the non-diseased crabs lacked lesions. Sediments within the contaminated area showed enrichment of arsenic, cadmium, manganese, titanium and vanadium relative to the uncontaminated area. Levels of aluminum, arsenic, cobalt, manganese, nickel, titanium, vanadium and zinc were significantly higher in both gill and hepatopancreas in crabs from the contaminated area. Manganese was always highest in the diseased crabs in all tissues measured. The concentrations of the remaining elements were greater in the gills of diseased crabs, while highest values of these elements in the hepatopancreas varied among the diseased and non-diseased crabs from the polluted area. Conversely, copper levels were always highest in all tissues in crabs from the uncontaminated area, and typically lowest in the diseased crabs. Concentrations of aluminum and arsenic were also significantly greater in the muscle tissue of crabs from the contaminated area, but no distinct trend was evident with regard to diseased versus non-diseased crabs. Arsenic was the only element accumulated by crabs in the contaminated area which has a known toxic affect on the tissue responsible for cuticle synthesis and repair (hypodermis) in crustaceans. Metals also accumulated could possibly act synergetically to compromise normal metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456780 TI - Anodontites trapesialis: a biological monitor of organochlorine pesticides. AB - The mussel Anodontites trapesialis (Lam, 1819) was used as an indicator of organochlorine pollutants in the Pardo River, located in the municipality of Ribeirao Preto (21 degrees 07'S and 47 degrees 45'W), State of Sao Paulo, Brazil. Biological monitoring was performed for one year at the site of a sugar cane grove on the left bank of the river. Forty-three animals were placed in two aluminum enclosures on the river bottom at this site and 4 animals of each enclosure were sacrificed for pesticide analysis at 3-month intervals, each collection corresponding to one season of the year. The animals were found to have been exposed to DDT, lindane, heptachlor, aldrin and dieldrin. Endrin was not detected in any of the analyses. PMID- 1456782 TI - Chronic ecotoxicity of copper and cadmium to the zebra mussel Dreissena polymorpha. AB - In order to evaluate ecological consequences of the long-term presence of metals in aquatic ecosystems, we investigated the filtration rate and survival of zebra mussels (Dreissena polymorpha) during chronic exposure to Cu and Cd. The filtration rate was measured once a week in laboratory experiments lasting 9-11 weeks. The lowest Cu concentration tested (13 micrograms/L) did not affect the filtration rate and survival of D. polymorpha, but the lowest Cd concentration (9 micrograms/L) did affect the filtration rate, but had no effect on survival. The EC50 for Cd decreased markedly from 388 micrograms/L to 27 micrograms/L when the exposure time was lengthened from 48 hours to 10 weeks. The largest decrease in EC50 for Cd was observed during the first week of exposure. In contrast, the EC50 for Cu did not decrease with increasing exposure time (chronic EC50: 43 micrograms/L). Since the chronic LC50 for Cd was 130 micrograms/L, the filtration rate appeared to be a far more sensitive endpoint for ecotoxicological laboratory experiments than mortality. D. polymorpha was capable of regulating the body concentration of the essential metal Cu at low concentrations in the water (13 micrograms/L). Cd was accumulated at every Cd concentration in the water, suggesting that Cd could not be regulated by D. polymorpha. It is concluded that the relation between short-term and long-term ecotoxicity was different for each metal and could not be predicted from the results of the short-term experiments. PMID- 1456783 TI - Temporal and spatial variation in the amount of cadmium in the phantom midge larvae (Chaoborus spp.). AB - Several factors, including body size, age, and temporal and spatial variation, which may influence the amount of cadmium (Cd) in the phantom midge larvae, Chaoborus spp., were examined in eight lakes, four from south-central Ontario (Dorset Region) and four from northwestern Ontario (Experimental Lakes Area). All three species of Chaoborus (C. punctipennis, C. trivittatus, C. flavicans) found in Chub Lake (south-central Ontario), were analyzed seasonally. One species, C. punctipennis, was collected and analyzed from all lakes. Smaller Chaoborus tended to have higher Cd concentrations (micrograms Cd/g dry weight), and lower Cd burdens (ng Cd/Animal) than larger Chaoborus. The Cd concentrations of Chaoborus in Chub Lake were lowest during the summer, which coincided with the fastest growth of the organisms. The Cd burdens differed between species, which was attributed to differences in their asynchronous life histories. Cadmium burdens and concentrations were significantly lower in the organisms from northwestern Ontario than those from south-central Ontario. Lower atmospheric deposition rates, lower Cd concentrations in the lake water, as well as life history differences, may explain these results. PMID- 1456784 TI - Long-term effects of heavy metals in food on developmental stages of Aiolopus thalassinus (Saltatoria: Acrididae). AB - Newly hatched F1 nymphs of Aiolopus thalassinus (Fabr.) were fed on food treated with various concentrations of HgCl2, CdCl2, and PbCl2 until the end of adult life. Toxicological observations were followed in the F1 generation and in the F2 generation derived from the heavy metal-loaded F1 parents. The highest concentration of the heavy metal caused 100% mortality of the F1 adults within four weeks. The nymphal duration of the F1 and F2 generations was significantly prolonged after Hg and Cd exposure, but the F1 of the group treated with lead was not affected. The fresh body weight of adults was significantly reduced in the F1 generation of most treatments and in the resulting untreated F2. The lifespan of the F1 adults was shortened. In the F2 generation, although the lifespan was somewhat longer, generally it was still shorter than that of the control adults. The mean egg number laid by F1 adults fed on food contaminated with Hg or Cd was decreased. This decrease was more pronounced in the case of Cd than Hg. In the females fed on food treated with Pb the reduction of the number of egg pods was not remarkable. The hatchability of the eggs laid by F1 females was significantly reduced as compared to the control. The viability of the eggs laid by F2 adults was somewhat decreased due to either a reduced number of egg pods or to a lower rate of hatchability, especially in the case of Cd. The treated adults frequently displayed weakness in their legs, difficulties in walking, tremors, and nervous movements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456786 TI - Nurses' challenges are great in caring for patients with diabetes. PMID- 1456785 TI - Mercury concentrations in seabirds from colonies in the northeast Atlantic. AB - Total mercury concentrations were determined in samples of body feathers from a range of common seabird species breeding at Latrabjarg, northwest Iceland, St. Kilda, Foula and the Firth of Forth, Scotland and Bleiksoy, Syltefjord, and Hornoy, Norway. Seabirds from Latrabjarg generally exhibited the highest mercury concentrations, with a trend of decreasing mercury concentrations in a southwest to northeast direction in seabirds at the other colonies; seabirds at Hornoy were generally found to have the lowest mercury concentrations. Some species at the Firth of Forth exhibited relatively elevated mercury concentrations compared to those at Foula and Norwegian sites. Inter-colony differences in diet were thought to be relatively small for most species and unlikely to account for the range of mercury concentrations measured in the seabirds (Latrabjarg: lowest arithmetic mean mercury concentration in common guillemots Uria aalge, 1.6 micrograms/g, s.d. = 0.6, n = 45; highest arithmetic mean mercury concentration in kittiwakes Rissa tridactyla, 5.5 micrograms/g, s.d. = 1.7, n = 36). The oceanic transport of mercury, together with the effects of anthropogenic inputs of mercury to the northeast Atlantic, and the removal of mercury from the water column via biological activity are discussed as influential factors determining the observed patterns of mercury concentration in seabirds. PMID- 1456787 TI - Licensure of advanced nursing practice. PMID- 1456788 TI - Psychosocial correlates of diabetes and renal dysfunction. AB - Psychosocial issues related to diabetes and renal dysfunction are complicated and many times misunderstood. Building relationships and acquiring relevant information from patients will help patients adjust to disease complications and enhance compliance. PMID- 1456789 TI - Chronic complications of diabetes mellitus: peritoneal dialysis. AB - As the number of patients with diabetes treated by peritoneal dialysis continues to grow, nurses will increasingly be challenged to assist these patients to prevent, manage and adapt to the chronic complications of diabetes, including microangiopathy, macroangiopathies and neuropathies. This article presents nursing assessments and interventions related to these chronic complications to hopefully enhance the quality of life for these patients. PMID- 1456790 TI - Dietary modifications: impact on diabetic nephropathy. AB - This article encompasses the topic of dietary impact upon the diabetic individual with the condition of diabetic nephropathy. The influence of diet will be addressed in: renal insufficiency, chronic renal failure, and the modalities of hemodialysis, peritoneal dialysis, and renal transplantation. The two-fold purpose of this review is to provide documentation in support of dietary therapy and to underscore the sharp contrast in nutritional needs dependent upon the individual's clinical status. PMID- 1456791 TI - Long-term effects of hemodialysis in diabetic patients with end stage renal disease. AB - The long-term effects of hemodialysis in diabetic patients with end stage renal disease (ESRD) may seem minor, yet with further examination are seen to touch every aspect of the patients' lives. The long-term effects range from vascular access issues, complications such as limb amputation, to feelings of loss of control as well as hopelessness and powerlessness. This article will highlight how the long-term outcomes and effects of hemodialysis with diabetes cause multisystem problems and multiple complications in patients. PMID- 1456792 TI - Early transplantation for patients with diabetic nephropathy. AB - Renal transplantation is often the preferred renal replacement modality for individuals with the complex problem of diabetic nephropathy. Referral to a transplant program before renal replacement therapy is needed allows patients an opportunity to make treatment decisions as well as offer the advantages of early transplantation. In addition to routine post-transplantation surveillance, health care after transplantation is directed towards prevention and management of diabetic sequelae. PMID- 1456793 TI - Kidney-pancreas transplantation: a treatment option for ESRD and type I diabetes. AB - Combined kidney-pancreas transplantation is a safe and effective treatment option for patients with end stage renal disease (ESRD) resulting from type I diabetes. Current 1 year graft survival rates are nearing 80% and evidence is accumulating that improvement occurs in microvascular and neuropathic complications of diabetes after transplantation. This article is a detailed overview based on the current literature and our experience at The University Hospitals of Cleveland of the challenges and benefits of kidney-pancreas transplantation and the nursing care required to prepare the patient for home. PMID- 1456794 TI - Pancreas transplantation: detecting rejection and patient care. AB - Pancreas transplantation in the type I diabetic patient offers hope for a normoglycemic state and arrest, or in some cases, reversal, of secondary complications of diabetes. Rejection in the pancreas graft can be difficult to detect, but much work is being done on different methods to recognize rejection. Patients report increase in psychological well-being after pancreas transplantation. Because of the benefits, it is a viable option for treatment of the patient with type I diabetes. PMID- 1456795 TI - Vascular changes in renal transplant allograft in the type I diabetic. PMID- 1456796 TI - Diabetic ESRD patient supported with intradialytic parenteral nutrition. AB - The patient did meet the expected outcomes. She was able to achieve a desired weight and continues to gain weight. Currently, consideration is being given to discontinuing IDPN therapy. The main concern is an exacerbation of her symptoms, which is often a problem with diabetic gastraparesis. BC's outlook on life is more positive. Hopefully, she will continue to be compliant with her diet, experience no increase in symptoms, and maintain this weight. As with all ESRD patients, her fluid status requires monitoring. Fluid gains are removed and she remains free of complications. BC is now able to participate in usual daily activities. She goes out to the hairdresser once a week and attends Sunday morning church service. Her sense of well-being is greatly improved. BC has expressed gratitude on numerous occasions for the treatment that she feels has saved her life. Her deteriorating physical state was severely affecting her emotional well-being. Her quality of life has been favorably altered by the intervention with IDPN therapy. PMID- 1456797 TI - Nursing guidelines for muromonab-CD3 (OKT3). AB - Muromonab-CD3 is currently being used in transplant patients to prevent or reverse graft rejection. It is important that nursing guidelines for its proper usage are understood before the administration of the drug. This article overviewed dosage considerations, side effect profile, and other nursing implications regarding the use of muromonab-CD3. PMID- 1456798 TI - Case management of the anemic patient. Epoetin alfa: focus on pediatric dialysis patients. AB - Although pediatric and adult dialysis patients experience similar symptoms, young patients can present special problems for clinicians. This article explores the management of pediatric patients receiving Epoetin alfa. PMID- 1456799 TI - Patient education: a commitment. PMID- 1456800 TI - [Destabilization of emulsions during extraction of antibiotics from natural solutions]. AB - Various means for changing the aggregative stability of emulsions in the system of benzylpenicillin fermentation broth filtrate and butyl acetate were tested. It was shown that the use of desemulgators was more efficient than the use of some means for removing the desemulgating admixtures. Moreover, addition of surface active substances after the preliminary thermocoagulation resulted in maximum decreasing of the emulsion aggregative stability. PMID- 1456801 TI - [Phage-mediated conjugative transfer of plasmids in Staphylococcus aureus]. AB - It was shown possible to transfer nonconjugative plasmids during joint cultivation of the donor and recipient cells by transduction and phage-mediated conjugation. In the latter case it was necessary that the phage in the medium was free and the prophage was present in the recipient cells. Differences in the regularities of the transfer of the nonconjugative plasmids mobilized by the conjugative plasmid or phage were observed. PMID- 1456802 TI - [Effects of rifampicin and doxycycline on the production of hydrogen peroxide by macrophages]. AB - The influence of rifampicin and doxycycline on oxidative metabolism of macrophages was estimated in vitro by production of hydrogen peroxide. It was shown that low concentrations of rifampicin and doxycycline stimulated production of hydrogen peroxide by macrophages of guinea pigs. In concentrations of 1 to 10 micrograms/ml corresponding to the mean therapeutic ones doxycycline increased both the spontaneous and zymosan-induced production of hydrogen peroxide by the macrophages. The potentiating activity of doxycycline on the cells activated by opsonized zymosan was higher. The maximum increase in the induced production of hydrogen peroxide (by 40 per cent) was observed when the antibiotic concentration was 1 microgram/ml. Rifampicin in concentrations of 0.1 to 1 microgram/ml corresponding to the mean therapeutic ones stimulated the zymosan-induced production of hydrogen peroxide by the macrophages. The maximum increase in the production of hydrogen peroxide (by 22 per cent) was noted at the rifampicin concentration of 1 microgram/ml. PMID- 1456803 TI - [Experimental study of human recombinant insulin]. AB - The experimental study of recombinant human insulin revealed its high specific activity. The kinetics of the hypoglycemic effect of various dosage forms of the insulin developed at the National Research Centre of Antibiotics and the dosage forms manufactured by Eli Lilly was similar. The pharmacological investigation of the dosage forms showed that they had no side effects on the vitally important organs and systems. It was concluded that the dosage forms of the gene engineered human insulin developed at the National Research Centre of Antibiotics did not differ by their characteristics from the analogous dosage forms manufactured in other countries. PMID- 1456804 TI - [Characteristics of pharmacokinetics of liposome-incorporated rifampicin in rats after intratracheal administration]. AB - Pharmacokinetics of rifampicin after its single intratracheal administration in the form of the liposome-encapsulated drug and its aqueous solution was studied on rats. It was shown that after the exposure to the liposome-incorporated rifampicin (10 mg/kg) the concentration-time curve in the blood and lungs was sigmoid with the retarded decrease in the blood drug concentration within 9 hours. The plateau segment of the curve provided at least a 4-fold longer maintenance of the rifampicin concentration in the blood and lungs at 3 to 4 micrograms/ml. The use of the liposome-incorporated antibiotic induced 2- and 1.5 fold increases in the AUC in regard to the lungs and blood, respectively. PMID- 1456805 TI - [Obtaining liposomal preparations of various biologically active substances by the method of detergent flow analysis]. AB - It was shown that detergent dialysis could be successfully used for liposomal encapsulation of substances belonging to different chemical groups with diverse therapeutic activity such as rifampicin, aclarubicin, amphotericin B, pefloxacin and insulin. Liposome encapsulation of substances poorly soluble or insoluble in aqueous media was likely the most promising. The optimal incorporation depended on both the composition of the lipids forming the liposomes and the properties of the compounds being encapsulated. PMID- 1456806 TI - [Antibacterial effects of gamma-interferon in experimental Klebsiella infection]. AB - The results of the experimental study on the effect of the natural and recombinant gamma-interferons (gamma-IFs) of mice on the process of the infection caused by Klebsiella sp. are presented. The infection was reproduced by intraperitoneal contamination of mice with a virulent culture of Klebsiella pneumoniae 5055, line SHK. The gamma-IFs were administered to the animals in a dose of 250 units per mouse on days 1 and 3 after the contamination. Survival of the animals, clearance of the pathogen from the blood and liver and functional activity of the phagocytes in the contaminated mice were investigated. It was shown that both the natural and recombinant gamma-IF stimulated the phagocytic activity and oxidative metabolism of the phagocytes in the contaminated mice. Activation of these functions after the use of the natural gamma-IF correlated with its marked protective effect and accelerated elimination of the pathogen from the host which was not observed after the use of the recombinant gamma-IF. PMID- 1456807 TI - [Ceftriaxone: world-wide experience with its clinical use]. PMID- 1456808 TI - [Prevention of surgical infection by using delayed- and non-delayed action antibiotics]. PMID- 1456809 TI - [Gentacycol--a delayed-action form of gentamicin in the treatment of suppurative infection]. AB - Efficacy of gentacycol was studied in the treatment of various purulent infections. It was used in therapy of hematogenic and traumatic osteomyelitis, wound infections, soft tissue abscesses, purulent diffuse peritonitis as a complication of comissural ileus or appendectomy, pyothorax, destructive pneumonia and mediastinitis. Gentacycol ++ was also used for the prophylaxis in cholecystectomy, herniotomy and other conditions. The favourable results were stated in 93 per cent of the cases. PMID- 1456810 TI - [Antibiotic therapy of children in a gnotobiological unit]. AB - The clinical effect of antibiotics in treatment of children at the age of 2 months to 5 years with acute pneumonia during a gnotobiological department in the wards of the 1st class purity and under the conditions of a routine pediatric hospital was estimated. The course of the antibiotic therapy amounted to 4.7 +/- 0.42 days in the gnotobiological department and 12.0 +/- 0.3 days in the routine hospital. After recovery the patients were discharged in 7.61 +/- 0.76 days from the gnotobiological department and in 15.2 +/- 1.11 days from the routine hospital. PMID- 1456811 TI - [Antibiotic therapy of Salmonella infection in infants during the first year of life and methods if its correction]. AB - The efficacy of antibiotic therapy of salmonellosis was studied and functional activity of peripheral blood leukocytes from electron microscopic data was estimated in 200 infants. It was shown that the use of antibiotics in combination with immunostimulants such as leukocyte mass, lysozyme and prodigiozan in complex therapy of salmonellosis in infants had a favourable effect on both the time course of the clinical signs and the functional state of the neutrophil leukocytes. The duration of the treatment decreased by 6.14 +/- 0.34 days and repeated isolation of the pathogen from the host appeared to be less frequent. PMID- 1456812 TI - [Experience with using aclarubicin in the treatment of acute leukemia and blast crisis of chronic myeloid leukemia]. AB - The clinical efficacy of aclarubicin, an anthracycline antibiotic, was studied in 48 patients with leukemia. The antibiotic was used in the following combinations with cytarabine: "7 + 7", "5 + 5" and "7 & 3". A complete remission was stated in 14 (42.4 per cent) out of 33 patients with acute nonlymphoid leukemia, 6 (43 per cent) out of the 14 patients having relapses. The combined therapy was effective in 4 out of 5 pre-resistant patients. The "7 + 3" scheme was the most beneficial. The most common adverse reactions were nausea and vomiting. PMID- 1456813 TI - [Comparative evaluation of stability of benzylpenicillin in acid media of natural solutions and in culture fluid]. AB - Inactivation of benzylpenicillin in real media i.e. fermentation broths and their filtrates was studied in comparison with the published data on inactivation of commercial benzylpenicillin in aqueous solutions as dependent on the medium pH and temperature. The lowest constant of benzylpenicillin inactivation was shown to be in the fermentation broths. PMID- 1456814 TI - [Cefoperazone in combination with metronidazole in the prevention of postoperative infectious complications in patients with genital neoplasms]. AB - Cefoperazone and metronidazole were used for the prevention of postoperative infectious complications in 33 patients (Group 1) with cervical cancer who had undergone the Wertheim operation. 29 patients (Group 2) were treated prophylactically with carbenicillin in the routine doses. Postoperative urinary infections developed in 12.1 and 37.9 per cent of the patients in Groups 1 and 2, respectively. Since the incidence of infectious complications in the patients of Group 1 was lower, the radiation therapy was initiated on an average on day 12.4 +/- 0.4, which was much earlier than in Group 2 (day 15.4 +/- 0.8, p < 0.001). Bacteriological examination of the operation materials from the patients of Group 1 revealed the presence of anaerobes in 64.3 per cent of the patients. The incidence of fever (over 37.8 degrees C) developed irrespective of other signs of an infection significantly correlated with the detection rate of anaerobes in the operation materials (p < 0.05). PMID- 1456815 TI - [Experience with using cefoperazone in cancer patients after bone marrow transplantation]. AB - Cefoperazone is a semisynthetic cephalosporin of the 3rd generation (cefobid, Pfizer, USA). It was used in monotherapy of 12 oncological patients during ++post cytostatic aplasia of the bone marrow and peripheral pancytopenia after bone marrow transplantation. The results were favourable in 67 per cent of the patients: the body temperature normalized and no signs of any infection were evident. In 25 per cent of the patients the monotherapy failed and it was necessary to combine cefoperazone with aminoglycosides. Therefore, cefoperazone proved to be an efficient antibacterial drug, whose use was possible in the monotherapy of oncological patients after transplantation of the bone marrow. PMID- 1456816 TI - [The place of cefoperazone in antibacterial therapy]. PMID- 1456817 TI - [Use of cefoperazone in clinical practice]. AB - The bacteriological and clinical efficacy and side effects of cefoperazone were studied in 45 patients with severe and moderate purulent inflammatory diseases. The study showed that its bacteriological and clinical efficacy was high in cases with peritonitis, cholecystitis, respiratory and urinary infections, as well as those of the eye and soft tissues. The general clinical efficacy amounted to 95.6 per cent. The number of the side effects was insignificant. This made it possible to recommend the use of cefoperazone in the therapy of many purulent inflammatory diseases, as well as in empirical therapy. PMID- 1456818 TI - [Preparation and characteristics of protoplasts from various strains of Streptomyces roseoflavus var. roseofungini]. AB - It was shown that the variants of the roseofungin-producing organism, which differ in their differentiation, antibiotic activity, structure and cell wall composition had different sensitivity to the protoplasting factors. The protoplasting increased the population heterogeneity: in strain 1128 it was evident from an increased frequency of the secondary colonies, in variant 1-68, folding of the colonies increased and their consistency become milder, sectorial colonies and colonies with coremia formed. It was in principle possible to transform the protoplasts of S. roseoflavus var. roseofungini by plasmid DNA, which suggests that the roseofungin-producing culture may be useful in genetic engineering. PMID- 1456819 TI - [Isolation and evaluation of the structure of the new anthracycline antibiotics rubomycins F and H]. AB - The rubomycin complex produced by Streptomyces coeruleorubidus 4-157 was studied and the two novel anthracyclines i.e. rubomycins F and H were isolated. The study of the physicochemical properties of the novel antibiotics in comparison with rubomycin C (daunomycin) and the specially prepared 3'-N-carbmethoxyrubomycin C showed that rubomycin F was 3'-N-carbethoxydaunomycin and rubomycin H was 3'-N carbmethoxydaunomycin. Therefore, rubomycins F and H are novel representatives of natural anthracyclines undescribed previously. PMID- 1456820 TI - [Search for inhibitors of West Nile virus among antibiotics]. AB - The activity of 24 antibiotics was studied in treatment of albino mice with experimental encephalitis caused by West Nile virus. The antiviral activity of gentamicin and kanamycin was stated. The survival rate of the animals 19. contaminated with 10-100 LD50 of the West Nile virus and treated parenterally with gentamicin in a dose of 80 to 400 micrograms/mouse was higher than that in the controls by 29.5 to 100 per cent and depended on the drug regimen. The efficacy of kanamycin was lower. The chemotherapeutic indices of gentamicin and kanamycin amounted to 100 and 10, respectively. Since there are no schemes for chemotherapy of the infection caused by the West Nile virus and the respective vaccines are not available the use of the antibiotics and gentamicin in particular appears to be promising in the disease prevention and treatment. PMID- 1456821 TI - [Clinical aspects of cefoperazone pharmacokinetics]. PMID- 1456822 TI - [Effect of doxorubicin on the functional state of the mononuclear phagocyte system]. AB - The response of the system of mononuclear phagocytes (SMP) to doxorubicin, an antitumor antibiotic, most widely used in oncological care, was studied. It was shown that a single intraperitoneal administration of doxorubicin to CBA mice in the maximum tolerance doses induced suppression of absorptive SMP capacity and increased IL-I secretion by the bone marrow and peritoneal macrophages both in the stimulated and spontaneous tests in early periods after cytostatic administration. There was a significant rise in the ability of SMP bone marrow elements to respond to the macrophage activating factor, as well as an increase in the cytotoxic activity of bone marrow and peritoneal macrophages. PMID- 1456823 TI - [Sensitivity of the pathogen of Campylobacter infection to various antibiotics]. AB - Antibiotic sensitivity of 21 Campylobacter strains isolated from humans, monkeys and birds with diarrhea was assayed and the findings are presented. It was shown that all the isolates were highly sensitive to ofloxacin, pefloxacin, ciprofloxacin, josamycin, pipemidinic acid and amoxyclav (a combination of amoxycillin and clavulanic acid). The predominating majority of the strains were resistant to rifampicin, amoxycillin and phosphomycin. The majority of the cultures were sensitive to erythromycin and roxithromycin while some of the isolates were resistant to them which could be used as an additional biological characteristic of Campylobacter cultures and considered in choosing agents for antibiotic therapy. PMID- 1456824 TI - [Use of a physiological model of gentamicin pharmacokinetics for individual dosage of the antibiotic]. AB - A new approach to fixing the initial doses of gentamicin (GM) for its intramuscular administration (the most commonly used anyway) is discussed. The approach is based on the physiological model reproducing the individual patterns of GM concentration change in patient's blood. Such parameters of the model as blood flow velocity and actual average volume of specific tissues as well as the tissue to the blood partition coefficient (Kp) are constant. They were used to calculate the volume of distribution in the body specific organs (Vs). The apparent distribution volume (Vd) and total clearance (Cl) are individual parameters. The Vd value was calculated individually for every particular patient depending on the body weight by the known equations. The difference between Vd and Vs was used to calculate the individual Kp for the organs and tissues which were not specially examined. When calculating Cl of GM, the patient's sex, age, weight and creatinine concentrations were taken into account. To evaluate the local velocity of blood flow after antibiotic intramuscular administration, it was important to consider the patient's sex and age. The approach was used to reproduce the individual patterns of GM concentration change after the initial administration of the antibiotic, 80 mg, to 19 male patients (age range, 21 to 73 years; weight range, 50 to 94 kg; blood creatinine concentration, 0.4 to 1.6 mg/dl). The GM concentrations attained with the use of the model were afterwards compared to the data on FPIA. (TDx, Abbott) by measuring the GM concentrations in the blood of the patients 0.5, 1, 5 and 7 hours after the administration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456825 TI - [Effect of combined preventive use of quadevit with antibiotics on the survival and humoral immune response in experimental studies]. AB - An attempt to correct with quadevit immunodepression due to prophylactic administration of benzylpenicillin and gentamicin for 6 days provided positive results. There was a significant increase in the quantities of Ig 19S and Ig 7S after the animal immunization with the bacterial antigen, an increase in the number of the AFCs in the spleen of the albino mice in response to administration of sheep erythrocytes and an increase in the survival rate of the animals with salmonellosis. The simultaneous use of quadevit with cefamezine and erythromycin did not lower the unfavourable influence of the antibiotics on the immune status of the animals. PMID- 1456826 TI - [Microbial ecology of laboratory animals as a model in evaluation of the immunomodulating and antimicrobial agents]. AB - Rats with altered microbial ecology and decreased colonization resistance due to neutropenia induced by cyclophosphamide were used as a model for estimating the effect of bacterial polysaccharides (lactulose and exopolysaccharide from Bacillus polymyxa) and fluoroquinolones (pefloxacin). Monotherapy with pefloxacin had a favourable effect both on normalization on the intestinal microflora in the rats and their hemopoiesis (decreased neutropenia). The highest correcting effect with respect to the lowered colonization resistance was observed when pefloxacin was used in combination with exopolysaccharide. PMID- 1456827 TI - [Therapeutic form of doxycycline hydrochloride for intravenous administration in the treatment of suppurative-septic diseases]. AB - Efficacy of doxycycline hydrochloride administered intravenously was studied in treatment of severe purulent inflammatory diseases such as pneumonia, lung abscesses, pyothorax, skin and soft tissue infections, peritonitis, purulent cholangitis, etc.. Doxycycline showed significant advantages over tetracyclines: prolonged action, higher efficacy and good tolerance. Favourable results were observed in 85 per cent of the cases. PMID- 1456828 TI - [Characteristics of the effect of myelosan on the immune status of patients with chronic myeloid leukemia]. PMID- 1456829 TI - [Aztreonam]. PMID- 1456830 TI - [Cefoperazone in a multi-profile surgical clinic]. AB - The results of the clinical trials of cefoperazone (cefobid, Pfizer, USA), a 3rd generation cephalosporin, carried out at the Research Centre of Surgery are presented. The antibiotic was used to treat and prevent postoperative infections in 44 patients. Good and satisfactory results were observed in 43 out of the 44 patients (99.9 per cent). Antimicrobial activity of cefoperazone against 182 bacterial strains isolated from the patients was assayed and compared with that of other cephalosporins i.e. cefotaxime, ceftriaxone and ceftazidime. The cefoperazone pharmacokinetics was studied in the patients with normal renal functions after surgical operations on the organs of the chest and abdominal cavity. The antibiotic was shown useful in the monotherapy of mixed infections involving anaerobic pathogens. PMID- 1456831 TI - [Prevention and treatment with cefoperazone of postoperative suppurative complications in heart surgery]. AB - Clinical trials of cefoperazone (cefobid, Pfizer, USA) were carried out in 49 patients with cardiovascular diseases who had undergone surgical operations. The pathogens of infectious complications were investigated bacteriologically. Good results of the treatment were observed in 43 patients. Allergic reaction developed in 1 patient. Cefoperazone was shown advantageous in treatment of pulmonary complications in the operated patients. It was found possible to use cefoperazone in combination with aminoglycosides. Cefoperazone was found to be one of the drugs of choice in the treatment of aerobic and anaerobic bacteriemia, as well as sepsis after surgical operations on the heart and great vessels. The results on the use of cefoperazone for short-term "perioperative" prophylaxis in cardiosurgery (in accordance with the WHO instructions) are also presented. PMID- 1456832 TI - The hypoosmotic swelling test: an update. AB - The hypoosmotic swelling (HOS) test is a relatively new assay used to evaluate the functional integrity of the sperm's plasma membrane. In fact, more studies have been published on the applicability of the HOS test than any other new sperm indicator. The assay is based on the fact that fluid transport occurs across an intact cell membrane under hypoosmotic conditions until equilibrium is reached. Due to the influx of fluid, the cell will expand and bulge, especially in the tail, and this change can be readily observed with a phase contrast microscope. Earlier studies have yielded some confusion regarding the interpretation of the data. This review is an attempt to clarify and update the usefulness of the HOS test as a tool to evaluate the sperm function. PMID- 1456833 TI - Antigenic differences in human sperm samples related to various morphological abnormalities. AB - Sperm samples were collected from male partners of fertile and infertile couples having unexplained and male factor infertility and analyzed for morphological abnormalities. After a staining procedure, sperm samples of these infertile men showed a variety of abnormalities. The sperm samples were also studied for their binding with the Abs directed against protamine (the nuclear protein), fertilization antigen (FA-1, sperm surface antigen), and the lithium diiodosalicylate- (LIS-) solubilized sperm preparation, and the binding was correlated with the percentage of morphologically abnormal sperm in the sample. Abs used in the present study were raised in female rabbits and had high titers (ELISA titers, 1:4096 to 1:8196), and recognized no band (anti-protamine), one 49,000- +/- 2000-dalton band (anti-FA-1), and at least 8 bands of various molecular identities in the 14,000- to 92,000-dalton range (anti-LIS sperm) on the Western blot of LIS-solubilized human sperm. The affinity-purified Fab' antibodies were iodinated and used in a radioimmunobindingassay for testing their binding with the sperm cells. Anti-protamine Fab's showed minimal binding and the binding activity (cpm bound/10 x 10(6) sperm cells) did not correlate (head defect, r = .12; midpiece defect, r = .07; tail defect, r = .11) significantly with percentage of abnormal cells in the sample. The binding of the anti-FA-1 Fab's also did not show a significant correlation (head defect, r = .29; midpiece defect, r = .48; tail defect, r = .23), though a positive trend (p = .05) was observed with the midpiece defect. In contrast, the binding of anti-LIS sperm Fab's demonstrated a significant correlation with the percentage of abnormal sperm cells in the sample (head defect, r = .51, p = .04; midpiece defect, r = .80, p less than .0001; tail defect, r = .23, p = .039). With an increased percentage of abnormal sperm cells, especially those with midpiece defect, there was an increased binding of anti-LIS sperm Fab's. These results suggest that with an increase in percentage of abnormal sperm, there is a change in antigenicity of the sperm cells. An increase in structural abnormality may enhance antibody binding to an abnormal sperm cell, thus causing a further decrease in its fertilizing capacity. PMID- 1456834 TI - The direct effect of Hochuekki-To on human sperm fertilizability using the hypoosmotic swelling test. AB - The concentration and motility of human sperm increase is examined following the oral administration of a traditional herbal medicine, Hochuekki-To using the hypoosmotic swelling (HOS) test. After 1 h incubation in Hochuekki-To, the motility of sperm and the results of the HOS test improved, particularly for severely abnormal sperm. For both the original and incubated sperm, the results of the HOS test improved when Hochuekki-To was used in the swim-up medium for the swim-up washing method rather than when Whittingham's T6 solution was used. Hochuekki-To had a favorable, direct effect on human sperm functions, suggesting an effect on the physiological integrity of sperm membrane. PMID- 1456835 TI - Effect of different types of textile fabric on spermatogenesis: electrostatic potentials generated on the surface of the human scrotum by wearing different types of fabric. AB - This study was conducted to evaluate the effect of the electrostatic potentials generated on the surface of the scrotal area when different types of textile fabric were worn. Twenty-one healthy volunteers were divided into three equal groups. The first group was dressed in underpants made of 100% polyester, the second wore underpants of 100% cotton, and the third wore a 50/50% polyester/cotton mixture. With an electrostatic kilovoltmeter, the electrostatic potentials were measured 1 h after wearing the pants once during the day and a second time at night. The test was repeated 4 times, each on a separate day. No electrostatic potentials were detected on the cotton underpants. The polyester pants showed the highest potentials (mean 338.9 +/- 25 SD V/cm2), while the mixed polyester/cotton pants produced less than half that level (mean 148.3 +/- 16 SD V/cm2). The readings during the day were higher than those at night, probably due to the higher temperature during the day. This study could explain the cause of diminished spermatogenesis in dogs dressed in polyester pants. A new theory is put forward holding that the polyester underpants create an "electrostatic field" across the scrotal sac that disturbs the testicular and/or epididymal function. PMID- 1456836 TI - Ultrastructural parameters of fertile cryopreserved human sperm. AB - Two hundred and forty-four cryopreserved semen samples were used for artificial insemination by donor (AID). All samples were examined for motility and concentration. Thirty of the samples resulted in pregnancies. These samples were further examined ultrastructurally. There was no difference in sperm motility or concentration between the samples that did or did not result in a pregnancy. The ultrastructural characteristics of the samples that resulted in pregnancies revealed that only 15% of sperm (SD = 7.67) possessed normal morphology and had undamaged acrosomes after cryopreservation. PMID- 1456837 TI - Effects of surgical repair of experimental left varicocele on testicular temperature, spermatogenesis, sperm maturation, endocrine function, and fertility in rabbits. AB - To evaluate the effectiveness of surgical correction of varicocele in restoring the function of the varicocelized testicle, experimental varicoceles were created in 16 male rabbits by partly ligating the left lumbotesticular trunk. Five control rabbits received a sham operation (group A). Two months later, eight of the varicocelized rabbits underwent surgical repair by ligation and cutting of the dilated left testicular vein (group B). The remaining eight varicocelized animals did not receive any additional treatment (group C). Five months after the initial operation, group C animals had a significantly lower sperm concentration, sperm motility, bilateral testicular androgen-binding protein activity, bilateral testicular vein testosterone concentration, bilateral testicular versus intraabdominal temperature difference, and fertility when compared with groups A and B. These findings suggested that the surgical repair of an experimental varicocele in the rabbit can significantly improve the parameters indicating the harmful effects of the varicocele on the testicles. PMID- 1456838 TI - Blood concentrations of lead, cadmium, mercury, zinc, and copper and human semen parameters. AB - The study consisted of 35 male subjects attending an andrology clinic. The subjects all had poor sperm parameters that could not be attributed to any known medical cause. The objective was to evaluate the relation between various seminal characteristics (volume, total sperm count, sperm viability, proportion of progressively motile sperm, and different sperm morphology) and the blood concentrations of lead, cadmium, mercury, copper, and zinc. The mean blood concentrations of lead, mercury, copper, and zinc were within the normal values; cadmium concentration (1.35 micrograms/L) was much higher than the norms. Asthenozoospermic subjects had significantly (p less than .025) higher blood cadmium levels than normozoospermic subjects. No significant differences were noted between the two groups for mean concentration of mercury, zinc, and copper in blood. Significant correlations were observed between blood cadmium levels and volume of semen, midpiece defects, and immature forms of spermatozoa. High blood cadmium levels may have an effect on spermatogenesis. Possible reasons for the high blood cadmium levels among the subjects are discussed. PMID- 1456839 TI - HPLC determination of an oxytocin-like peptide produced by isolated guinea pig Leydig cells: stimulation by ascorbate. AB - Highly purified populations of guinea pig Leydig cells were incubated with a maximally stimulating dose of 100 ng/mL LH for 24 h in the presence of increasing concentrations of sodium ascorbate. Sample supernatants were extracted, concentrated under vacuum, and reconstituted with acidified absolute ethanol. Samples were analyzed for oxytocin using high-performance liquid chromatography with electrochemical detection and known concentrations of an authentic oxytocin standard. Leydig cells stimulated with 0, 25, and 50 microM ascorbate produced and secreted 40.1 +/- 1.23, 77.4 +/- 13.8, 74.2 +/- 26.3 pg of an oxytocin-like peptide, respectively, per 1 x 10(6) cells. These results indicate that guinea pig Leydig cells are capable of producing an oxytocin-like peptide de novo and that low concentrations of ascorbate stimulate the production of this peptide in Leydig cells cultured in vitro. PMID- 1456840 TI - Developmental changes in testosterone production by the rat testis in vitro during late fetal life. AB - The age-related evolution of the in vitro capacity of the rat testis to produce testosterone and to respond to luteinizing hormone (LH) during 3 and 24 h incubation was studied from day 18.5 to day 21.5 of fetal life. Basal testosterone production by testes from 18.5-day-old fetuses was significantly higher than production by testes from 20.5- and 21.5-day-old fetuses when secretion was expressed as either per testis or per microgram of testicular protein. When maximal LH-stimulated testosterone secretion was expressed on a per testis basis, it was significantly lower for day 18.5 testes than for day 20.5 and 21.5 testes. However, when it was expressed on the basis of testicular protein content, it decreased significantly between days 18.5 and 20.5. Basal and LH-stimulated secretions displayed the same time-related decrease throughout 24 h of incubation for the three ages studied. The dose-response curves for LH showed that the sensitivity was similar for day 18.5 and 20.5 testes (ED50 = 10 vs. 14 ng/mL, respectively). These results showed an age-related decrease in testicular steroidogenic capacity without a change in the coupling efficiency of LH receptor to testosterone production during late fetal life in rats. PMID- 1456841 TI - The fate of foreign DNA associated with pig sperm following the in vitro fertilization of zona-free hamster ova and zona-intact pig ova. AB - The aim of this study was to determine the fate of foreign DNA molecules bound to porcine sperm that had been capacitated and acrosome reacted in vitro using calcium ionophore and then used in the in vitro fertilization of zona-free hamster ova and zona-intact pig ova. Fluoresceinated Pisum sativum agglutinin (PSA) labeling was used to differentiate between acrosome-intact and acrosome reacted sperm. This revealed that up to 80% of the sperm treated with calcium ionophore were acrosome reacted. Up to 70% of these acrosome-reacted sperm were labeled with the foreign DNA at the post-acrosomal region. Following association of DNA with the acrosome-reacted sperm, insemination droplets were prepared and zona-free hamster oocytes or zona-intact pig oocytes were added. The gametes were allowed to interact and then fixed and stained to visualize decondensed sperm heads that had penetrated into the oocytes. The sperm were stained with streptavidin peroxidases to detect the biotinylated foreign DNA bound to the decondensed heads. These studies revealed that 54% of fertilized hamster and pig oocytes contained decondensed sperm that had retained the post-acrosomal pattern of bound foreign DNA. After incubation with DNA-associated sperm, the oocytes were washed and cultured for 15-17 h. After fixation, up to 30% of hamster oocytes and 10% of porcine oocytes were found to contain sperm pronuclei. However, using the streptavidin peroxidase detection system, it was not possible to determine if any of these pronuclei contained the foreign DNA. PMID- 1456842 TI - Classification of compounds for prevention of NMDLA-induced seizures/mortality, or maximal electroshock and pentylenetetrazol seizures in mice and antagonism of MK801 binding in vitro. AB - Intravenous injection of N-methyl-D,L-aspartic acid (NMDLA) into mice produces characteristic convulsions followed by death. The present study was designed to determine the degree of blockade of these seizures/mortality by compounds acting at various subsites on the N-methyl-D-aspartic acid (NMDA) receptor complex (competitive and noncompetitive antagonists, as well as inhibitors of the strychnine-insensitive glycine subsite, and Zn++ subsite agonists), and also calcium channel blockers, clinically used anticonvulsants, plus selected compounds with activities or structures similar to specific agents chosen. Activity among compounds was correlated to in vitro potency regarding inhibition of binding of MK801 to the ionic channel subsite associated with the NMDA receptor. Furthermore, all compounds were examined for antiseizure properties with respect to tonic hindlimb extension elicited by maximal electroshock (MES) and clonus induced by pentylenetetrazol (PTZ). Drugs were subsequently classified according to their spectra of efficacy in these tests. The following characteristics emerged: 1) agents active at all 3 NMDA mechanisms (convulsions/mortality/MK801 binding) plus MES and PTZ, were MK801 and CPP [3-(2 carboxypiperazin-4-yl) propyl-1-phosphonic acid]; 2) active at all the NMDA mechanisms and MES were ketamine and dextromethorphan; 3) active against NMDLA induced convulsions/mortality, MES and PTZ, but not MK801 binding, were doxepin, desipramine and diazepam; 4) active against NMDLA-induced convulsions/mortality and MES were des-Me-doxepin, flunarizine and remacemide; 5) active against NMDLA induced convulsions/mortality and PTZ was nisoldipine; 6) active against only NMDLA-induced convulsions/mortality were chlorpheniramine and iproniazid; 7) active in the MES and PTZ tests were phenobarbital, pentobarbital and valproate; 8) active in the MES test alone were phenytoin and carbamazepine; 9) active against PTZ only was ethosuximide; 10) active only in the in vitro MK801 binding assay were HA966, 7-Cl-kynurenate and AP7 (2-amino-7-phosphonoheptanoic acid); and 11) no demonstrable actions had AP4 (2-amino-4-phosphonobutyric acid) and mianserin. In conclusion, inhibition of NMDLA-induced convulsions/mortality in vivo is not necessarily correlated to a noncompetitive displacement of MK801 binding to NMDA receptor sites in vitro, nor is inhibition of NMDA-elicited convulsions/mortality correlated with a specific ability of a compound to inhibit either MES or PTZ seizures. PMID- 1456843 TI - Effects of clonazepam on paired-pulse and frequency potentiation of evoked potentials in rats. AB - Three different monosynaptic evoked potentials (thalamocortical, interhemispheric, i.e. transcallosal, and entorhino-dentate) were used to study the paired-pulse and frequency potentiation in adult rats. A marked potentiation was seen in both neocortical responses under control conditions (up to 200%), whereas potentiation in the dentate gyrus was only moderate. Clonazepam (0.1 and/or 1 mg/kg, i.p.) antagonized the potentiation of the thalamocortical responses only, the frequency potentiation was suppressed in a dose-dependent manner, and the paired-pulse potentiation was significantly attenuated only by the higher dose of clonazepam. The potentiation of the cortical interhemispheric as well as of the entorhino-dentate evoked potentials was not changed by either dose of clonazepam. The present results do not form the hypothesis of frequency potentiation as a mechanism of epileptogenesis. PMID- 1456844 TI - Pumiliotoxin B-like alkaloid in extracts of the skin of the Australian myobatrachid frog Pseudophryne coriacea: effects on blood pressure and heart of the rabbit. AB - Extracts of the skin of the Australian myobatrachid frog Pseudophryne coriacea (PS) displayed striking, reversible and, in part, dose-dependent effects on the systemic blood pressure and the heart of the rabbit. Similarly to the results obtained in the rat, the blood pressure response in the rabbit consisted in an initial short-lasting fall, followed by a significant and persistent rise. The initial hypotensive effect was inhibited by atropine, indicating a cholinergic mechanism. The inhibition of the pressure rise by prazosin or guanethidine, but not by surrenalectomy or hexamethonium, suggests a catecholamine release from adrenergic nerve terminals of the vasculature. PS produced on the heart a variety of rhythm disorders, caused both by a release of acetylcholine and a direct effect on the myocardium. It is worth mentioning that tetrodotoxin, a typical sodium channel blocker, reduced or abolished the effects of PS both on the heart and the blood pressure, suggesting that sodium channels may directly or indirectly participate in the mechanism of action of PS. PMID- 1456845 TI - Inhibition of neutrophil chemotaxis by purinoceptor agonists. AB - Adenine nucleotides inhibited fMet-Leu-Phe-activated chemotaxis by rabbit neutrophils in the micromolar concentration range. The sequence of inhibitory effectiveness was ATP[S] greater than ATP greater than ADP greater than AMP greater than adenosine. In the presence of EDTA, inhibition of chemotaxis by ATP occurred to the same degree as in the presence of Ca2+ (and Mg2+), indicating that neither ectonucleotidases nor Ca2+ fluxes across the plasma membrane are of importance for the inhibitory effect. The inhibitory effect of ATP persisted when the nucleotide was removed after preincubation, before the cells were submitted to chemotaxis. Exposure of neutrophils to ApCpp results in desensitization towards inhibition by ATP. Other nucleoside triphosphates, such as XTP, GTP, ITP, CTP and UTP, also inhibited neutrophil migration. The relative potency of the nucleotides, which are used to discriminate between the subtypes of the P2 purinoceptor, was (at a concentration of 50 microM) ATP greater than ApCpp greater than AppNp greater than MeSATP greater than AppCp. The results suggest that inhibition of neutrophil chemotaxis by purinoceptor agonists is mediated by P2 purinoceptors and that the subtype is different from the P2x or P2y purinoceptor. PMID- 1456846 TI - Barriers to following National Cholesterol Educational Program guidelines. An appraisal of poor physician compliance. PMID- 1456847 TI - Ceasing futile resuscitation in the field: ethical considerations. PMID- 1456848 TI - Screening for cancers of the lung and colon. PMID- 1456849 TI - Screening for cancers of the cervix and breast. PMID- 1456850 TI - Distribution of lipid phenotypes in community-living men with coronary heart disease. High prevalence of isolated low levels of high-density lipoprotein cholesterol. AB - BACKGROUND: Risk factor modification, including treatment of dyslipidemias, has been recommended for the prevention of future coronary events in patients with coronary heart disease (CHD). Since the prevalence of various dyslipidemias among outpatients with CHD has not been well documented, the purpose of this study was to determine the frequency of specific lipid phenotypes among ambulatory men with CHD. METHODS: Lipid profiles were obtained in 255 men (mean age, 65.5 +/- 9.1 years) with CHD in three Veterans Affairs medical centers. Desirable levels of lipids were defined according to National Cholesterol Education Program guidelines as follows: low-density lipoprotein cholesterol (LDL-C) levels less than 3.36 mmol/L (130 mg/dL); high-density lipoprotein cholesterol (HDL-C) levels equal to or greater than 0.90 mmol/L (35 mg/dL); and triglyceride levels less than 2.83 mmol/L. RESULTS: Seventy-six percent of the group had one or more abnormalities on lipid profile: 51% had high LDL-C levels with or without abnormalities of HDL-C and/or triglyceride levels; 22% had low HDL-C levels with desirable levels of LDL-C; and 3% had hypertriglyceridemia without any cholesterol abnormalities. Normal lipid profiles were significantly more prevalent in subjects over the age of 65 years than in younger patients (40% vs 14%). CONCLUSIONS: These data suggest that (1) a high proportion of men with CHD have dyslipidemia, including 50% with LDL-C level elevations. For these men, the potential benefits of therapeutic intervention have been documented in clinical trials, although the cost-efficiency of wide-scale treatment has not been determined; (2) isolated hypertriglyceridemia is rare in this population; and (3) low HDL-C levels in association with desirable LDL-C levels are present in more than one fifth of male patients with CHD. Clinical trials focusing on this large group are urgently needed to determine whether efforts to raise HDL-C levels result in reduced cardiac morbidity and/or mortality. PMID- 1456851 TI - How useful is the rheumatoid factor? An analysis of sensitivity, specificity, and predictive value. AB - BACKGROUND: The rheumatoid factor (RF) is frequently ordered in an effort to detect disease, yet its diagnostic utility has not been thoroughly examined. To determine the test's sensitivity, specificity, positive predictive value, and negative predictive value, we analyzed tests ordered in our institution. METHODS: We performed a retrospective analysis of all 86 patients with a positive RF over a 6-month period identified consecutively soon after the test was ordered. A similar analysis was applied to 86 seronegative patients selected at random from a total seronegative population of 477 during the same period. The patients represented the primary care and subspecialty practices and inpatient wards of a 504-bed university teaching hospital. RESULTS: A positive RF result was strongly associated with rheumatoid arthritis or another rheumatic disease. For rheumatoid arthritis, sensitivity = 0.28 and specificity = 0.87, while for any rheumatic disease, sensitivity = 0.29 and specificity = 0.88. The positive predictive values for rheumatoid arthritis and any rheumatic disease were 0.24 and 0.34, respectively, and the negative predictive values were 0.89 and 0.85, respectively. Seropositive patients were slightly older (55 vs 49 years old), but the incidence of false-positive RFs among the elderly (69%) was not significantly higher than among younger patients (65%). The cost per true-positive RF result was $563. CONCLUSIONS: In this study, most positive RF results were not helpful since the majority represented false-positive results. The low positive predictive value of the RF casts doubt on the utility of the RF in the diagnostic evaluation of patients. Contrary to traditional clinical expectations, the diagnostic utility of the RF may be greatest when it is negative. However, the subset of patients with seronegative rheumatic disease reduces the test's power to exclude such disorders even when the RF is negative. Given the test's limitations, clinicians should reconsider their expectations when ordering an RF. The utility of the RF may improve if it is ordered more selectively. PMID- 1456852 TI - Mandated choice. The preferred solution to the organ shortage? AB - BACKGROUND: A critical shortage of organs is perhaps the major barrier facing transplantation today. Adopting a system of presumed consent or mandated choice are among the solutions proposed. Under presumed consent, organs may be removed after death without explicit consent, unless the deceased had previously objected or the family objects at the time of death. Under mandated choice, all adults would be required to decide for themselves whether they wish to donate on their deaths and their decisions would be controlling. METHODS: To see if educated young people would support these proposals, I carried out two surveys at the University of Maryland, College Park, Md, of a total of 418 students who were at least 18 years of age. RESULTS: An overwhelming 90% would support mandated choice while a smaller percentage, just over 60%, would support presumed consent. The vast majority believe that the family should not be able to override the previously expressed wishes of their recently deceased loved one. Unfortunately, only a minority of respondents had discussed organ donation with their families and even fewer had signed donor cards. CONCLUSIONS: Even young, educated people frequently fail to consider organ donation prospectively and this is a major barrier to organ retrieval. While presumed consent and mandated choice are designed to deal with this serious problem, mandated choice seems preferable and would likely receive widespread support. Therefore, I suggest that a small scale trial of mandated choice be undertaken as soon as possible in the hope of finding an acceptable system that will quickly and efficiently increase the supply of desperately needed organs. PMID- 1456853 TI - The complications of infective endocarditis. A reappraisal in the 1980s. AB - BACKGROUND: The frequency of complications of infective endocarditis and their influence on the outcome of the patients changed in the antibiotic era. Therefore, we evaluated the complications in a recent large series of patients with infective endocarditis. METHODS: We studied 300 episodes of endocarditis in 287 patients in a tertiary cardiology referral center. Predisposing cardiac conditions were valvular heart disease in 147 episodes, congenital heart disease in 37, other heart diseases in five, and prosthetic heart valves in 69. In 69 episodes, there was no previous heart disease. The infecting microorganisms were streptococci in 147 episodes, Staphylococcus aureus in 59, Staphylococcus epidermidis in 14, gram-negative bacteria in 16, other gram-positive bacteria in eight, and fungi in four. In 52 episodes, blood cultures were negative. Seventy eight patients (26%) died. Complications were defined as any clinically unfavorable event occurring during treatment. RESULTS: A total of 386 complications occurred in 223 episodes (74%); one complication occurred in 128 episodes (57%), two in 57 (26%), three in 18 (8%), four in 13 (6%), five in three (1%), and six or more in three (1%). The complications were as follows: cardiac, 100 occurrences; neurological, 72; septic, 46; associated with medical treatment, 41; renal, 27; extracranial systemic arterial embolism, 16; septic pulmonary embolism, 26; complications related to surgical treatment, 11; acute prosthetic heart valve insufficiency, six; splenic infarction or abscess, three; cardiac rhythm disturbances, three; and other, 19. The distribution of the complications relative to outcome of the patients revealed that fatality exceeded survival rates for neurologic and septic complications. CONCLUSIONS: Complications may be common in patients with infective endocarditis. Cardiac complications were the most common ones, but fatality rates were higher for neurologic and septic complications. Hence, heart failure was replaced by neurologic and septic complications as the leading causes of death in patients with infective endocarditis. PMID- 1456854 TI - Prognosis in ischemic heart disease. Can you tell as much at the bedside as in the nuclear laboratory? AB - BACKGROUND--While the resting left ventricular ejection fraction (LVEF) predicts prognosis in ischemic heart disease, clinical evaluation is also useful. METHODS- To compare the prognostic value of LVEF by resting radionuclide ventriculography with that of clinical signs and symptoms of congestive heart failure (CHF), 170 patients with suspected ischemic heart disease were followed up in this prospective study. Patients had a standardized history and physical examination performed by a study cardiologist immediately before the nuclear scan. Chest roentgenography and radionuclide ventriculography were performed in a standard manner. The diagnosis of CHF was made by validated clinicoradiographic criteria based on the Framingham study. Mortality was determined by means of the National Death Index; median follow-up time was 3 years. RESULTS--There was CHF at baseline in 70 patients, and baseline LVEF was low (< or = 0.4) in 63 patients. Low LVEF was significantly associated with CHF. During follow-up, 55 of the subjects died (overall mortality, 32%). Subjects with CHF had a significantly higher risk of death than those without CHF, and subjects with low LVEF had a higher mortality than those with preserved LVEF. Both CHF and LVEF were independent predictors of mortality. In a Cox model, each percentage increase in LVEF was associated with a 2% decreased mortality, while subjects with CHF had a mortality 2.5 times higher than that of those without CHF. Also, CHF with preserved LVEF had a better prognosis than CHF with depressed LVEF, but this prognosis was worse than that in subjects without CHF. CONCLUSIONS--The clinical diagnosis of CHF, based on clinical evaluation and chest roentgenogram, is a valid predictor of mortality and provides information independent of the radionuclide LVEF in determining prognosis in patients with ischemic heart disease. PMID- 1456855 TI - Cholesterol-lowering effects of calcium carbonate in patients with mild to moderate hypercholesterolemia. AB - BACKGROUND: In recent years, several authors have noted that oral calcium treatment was associated with a reduction in serum cholesterol level. METHODS: Calcium carbonate was examined for its ability to lower serum cholesterol levels in hypercholesterolemic patients. Fifty-six patients with mild to moderate hypercholesterolemia were examined in this randomized, double-blind, placebo controlled crossover study. Patients were treated with a low-fat, low-cholesterol diet targeted at the American Heart Association Step-1 diet for 8 weeks before and while receiving placebo or calcium carbonate (9.98 mmol [400 mg] of elemental calcium) three times daily with meals for 6 weeks. Patients were then crossed over to the alternate treatment for an additional 6-week period. RESULTS: Compared with placebo, calcium carbonate achieved a 4.4% reduction in the low density lipoprotein cholesterol level, and a 4.1% increase in the high-density lipoprotein cholesterol level. The ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol significantly decreased by 6.5% with calcium carbonate treatment. Calcium carbonate treatment did not significantly affect blood pressure or serum levels of triglycerides, lipoprotein Apo B, or calcium. Relative urinary saturation ratios of calcium oxalate levels were unchanged during calcium carbonate therapy. Compliance with diet and treatment was excellent and no significant adverse effects were noted. CONCLUSIONS: Thus, calcium carbonate was a modestly effective and well-tolerated adjunct to diet in the management of mild to moderate hypercholesterolemia in this clinical study. PMID- 1456856 TI - Prevalence of, and risk factors for, angiographically determined coronary artery disease in type I-diabetic patients with nephropathy. AB - BACKGROUND--Thirty-five percent of type I-diabetic patients are dead of coronary artery disease by age 55 years, and the risk of death is increased eightfold to 15-fold in patients with nephropathy. However, the prevalence of coronary artery disease with respect to age is unknown and few risk factors have been identified. METHODS--One hundred ten insulin-dependent diabetic patients underwent routine pretransplant coronary angiography and cardiac risk factor assessment. Angiograms were evaluated by two angiographers for presence or absence of coronary artery disease (CAD, defined as one or more coronary artery stenoses of 50% or greater in diameter, and no CAD, defined as no stenosis of 25% or greater in diameter, respectively). Prevalence of CAD by age was determined, and associated risk factors were defined. RESULTS--Fifty-two of 110 patients had CAD. Coronary artery disease prevalence increased significantly with age; 13 of 16 patients older than 45 years of age had CAD. For patients 35 years of age or younger, associated risk factors included a family history of premature myocardial infarction, higher hemoglobin A1c level, hypertension for more than 5 years, lower high-density lipoprotein level, and smoking for more than 5 pack-years. For patients between 35 and 45 years of age, associated risk factors included number of years of diabetes, higher hemoglobin A1c levels, and smoking more than 5 pack-years. CONCLUSIONS--In type I-diabetic patients with nephropathy, CAD prevalence increased significantly with age and was found in the majority of patients older than 45 years of age. Coronary artery disease risk factors operative in the general population were significantly associated with CAD in this high-risk group. In addition, a role for hyperglycemia in accelerated atherogenesis was supported by the association of both higher hemoglobin A1c levels and number of years of diabetes with CAD. PMID- 1456857 TI - The effectiveness of cerebral imaging in the diagnosis of chronic headache. AB - OBJECTIVE: The increasing availability of high-resolution cerebral imaging scanners has fueled enthusiasm for their use to "rule out" brain tumor and other serious neurologic conditions in patients with headache. The effectiveness of this practice, however, has not been tested since the advent of newer scanning equipment. Our objective was to measure the usefulness of cerebral imaging in patients with chronic isolated headache. DESIGN: A retrospective study with a 15- to 27-month follow-up period. SETTING: A group-model health maintenance organization. PATIENTS: Adult patients, 100,800, in a health maintenance organization and an enriched sample of 63 patients with neurosurgical conditions from other health maintenance organization hospitals. RESULTS: During 1990, 1083 cerebral computed tomographic scans were performed on 863 adults (0.9% of health maintenance organization adults). Eighty-nine patients were scanned for chronic isolated headache; none of the scans provided important new information (95% confidence interval, 0%, 3%). Long-term patient follow-up confirmed that this low yield could not be attributed to diagnostic work-up bias. Further attempts to support a policy of imaging patients with isolated headache were also unsuccessful. Review of an enriched sample of patients with malignant brain tumor and patients requiring craniotomy for other reasons (n = 40) demonstrated that no patient had headache alone at the time of diagnosis (95% confidence interval, 0%, 8%) and that only 5% (95% confidence interval, 0%, 12%) of these patients sought medical attention for headache alone. Sampling a second enriched sample of patients who were referred from other hospitals (n = 63) because of conditions requiring neurosurgical procedures demonstrated that only 6% of patients presented with chronic isolated headache alone (95% confidence interval, 0%, 12%). Uncertainty regarding the appropriateness of imaging patients with headache was illustrated by the extreme interphysician variability of this practice. CONCLUSION: Our study demonstrates the large potential cost and low (although not zero) yield associated with nonselectively imaging patients with chronic isolated headache. PMID- 1456858 TI - Equal survival rates for first, second, and third episodes of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. AB - BACKGROUND: Second and subsequent episodes of acute Pneumocystis carinii pneumonia (PCP) are reported to have a worse prognosis than initial episodes in patients with the acquired immunodeficiency syndrome. We tested the hypothesis that survival rates of first, second, and subsequent episodes of acute PCP in patients with the acquired immunodeficiency syndrome are equal. METHODS: Analysis of the outcomes in prospective series of patients with the acquired immunodeficiency syndrome treated for acute PCP over 5 years. RESULTS: Survival rates of 222 PCP occurrences by episode number were: first, 86%; second, 84%; third, 88%; and fourth, 67%. Survival rates for the first, second, and third episodes were not significantly different. Second and third episodes had a larger proportion of patients with mild disease than initial episodes. CONCLUSIONS: Survival rates for first, second, and third episodes of PCP in patients with the acquired immunodeficiency syndrome are not different. In contrast to earlier articles, treatment for second and third episodes of acute PCP may be as successful as in initial episodes. PMID- 1456859 TI - Frequent hypoglycemic episodes in the treatment of patients with diabetic ketoacidosis. AB - BACKGROUND: Previous studies of the management of diabetic ketoacidosis have noted a wide range of incidence of hypoglycemia but have not studied the risk factors associated with it. METHODS: To describe the incidence of hypoglycemia in patients hospitalized with diabetic ketoacidosis, we retrospectively reviewed the charts of all adult patients with the diagnosis of diabetic ketoacidosis at three private, community hospitals in Milwaukee, Wis, between January 1, 1987, and May 31, 1990. Two hundred twenty admissions in 150 patients met our inclusion criteria. RESULTS: In 30% (66/220) of cases of diabetic ketoacidosis, a serum glucose level or Accu-Chek (Boehringer-Mannheim, Indianapolis, Ind) finding was 2.7 mmol/L or less during the first 14 days of hospitalization. No factors could be identified that were associated with a significantly increased risk of early hypoglycemia (within the first 48 hours of admission). The risk of a "late" occurrence of hypoglycemia (after 48 hours of hospitalization) was increased by fever (relative risk, 2.05; 95% confidence interval [CI], 1.16 to 3.63), "nothing orally" status (relative risk, 3.01; 95% CI, 1.88 to 4.83), hepatic disease (relative risk, 2.56; 95% CI, 1.39 to 4.70), and renal disease (relative risk, 2.07; 95% CI, 1.26 to 3.39). A logistic regression analysis showed "nothing orally" status to be associated with an increased risk of any hypoglycemia occurring during the hospitalization (relative risk, 2.39; 95% CI, 1.63 to 3.51). Physicians and nurses documented the first episode of hypoglycemia in their notes 45.5% and 80.3% of the time, respectively. CONCLUSION: Hypoglycemia is still a common complication of diabetic ketoacidosis, is associated with hepatic and renal disease as well as fever and "nothing orally" status, and is not documented well in physician notes. PMID- 1456860 TI - Toward improved empiric management of moderate to severe urinary tract infections. AB - BACKGROUND: Guidelines to show whether a patient hospitalized because of a urinary tract infection (UTI) has a severe infection, and whether he or she is at high risk for harboring a multiresistant pathogen, are scant. The aims of the present study were to find (1) clinical and laboratory variables known within 24 hours of admission that, combined in a logistic model, will point to a high or low probability of bacteremia and (2) variables that can be used to define patients at high risk for the subsequent isolation of a multiresistant uropathogen. METHODS: In a set of patients consecutively admitted to a department of medicine because of UTI, we compared bacteremic vs nonbacteremic patients, and patients with a multiresistant uropathogen vs others, on logistic regression analysis. The logistic models derived were validated in a second set of patients with UTI. RESULTS: Among 247 patients with UTI (median age, 75 years), 80 of them with bacteremia, five factors were significantly and independently associated with bacteremia: serum creatinine level, leukocyte count, temperature, diabetes mellitus, and low serum albumin level. A logistic model incorporating those factors was used to divide the patients into three groups with increasing prevalence of bacteremia (6%, 39%, and 69%) and of death (3%, 6%, and 20%). Three factors were predictive of the subsequent isolation of a resistant uropathogen: use of antibiotics before admission, advanced age, and male gender. The combination of those factors was used to divide patients into two groups, with resistance to cefuroxime of 9% vs 28%, to gentamicin of 7% vs 20%, and to sulfamethoxazole-trimethoprim of 30% vs 50%. In a second set of 144 patients with UTI, the percentages of bacteremia in the three groups were 5%, 16%, and 55%, and those of death, 2%, 6%, and 17%. When divided by the second model, the resistance to cefuroxime in the two groups was 16% vs 30%; to gentamicin, 16% vs 28%; and to sulfamethoxazole-trimethoprim, 28% vs 59%. CONCLUSIONS: If prospectively validated in other settings, the models can be used to define groups of patients with UTI at low and high risk for bacteremia, and to help in the choice of empiric antibiotic treatment. PMID- 1456861 TI - Efforts to improve compliance with the National Cholesterol Education Program guidelines. Results of a randomized controlled trial. AB - STUDY OBJECTIVE: We compared three approaches for improving compliance with the practice guidelines of the National Cholesterol Education Program (NCEP). DESIGN: A randomized controlled trial. SETTING: Academic group practices of a major urban teaching hospital. PARTICIPANTS: Study physicians were three equivalent groups of PG-2 and PG-3 residents (N = 33) seeing patients in equivalent outpatient clinics. Continuity patients of these residents were included (N = 240) if they were younger than 66 years, saw their primary physician during the intervention period, were not pregnant, and had no serious life-shortening noncardiac illnesses. INTERVENTIONS: Three interventions were implemented over a 5-week period. Control group physicians (group 1) were offered only a standard lecture provided through the Physician Cholesterol Education Program (PCEP). Group 2 physicians were offered the PCEP lecture and also received generic chart reminders of the NCEP guidelines on each eligible patient's chart. Group 3 physicians were offered the PCEP lecture and also received timely patient specific feedback, including acknowledgement of recent lipid values and management, and explicit recommendations for further action. Knowledge of lipid disorders was tested before and after the PCEP lecture, and physicians' attitudes were surveyed following the intervention period. MEASUREMENTS AND MAIN RESULTS: The three groups were similar in baseline (preintervention) compliance with NCEP recommendations (average, 39%) and physicians' knowledge. Patients were similar across groups in number of coronary artery disease risk factors and cholesterol values. Significant within-group improvements in compliance were noted for groups 2 and 3 (7.6% and 10.6%, respectively), but not for group 1 (4.5%). Importantly, there were no differences observed in improvements across groups. In exploratory analyses, however, there was a significant correlation between improved compliance and the number of patients seen by each provider in group 3 that was not observed in groups 1 or 2. Notably, changes in compliance were unrelated to PCEP lecture attendance (8.6% vs 8.1% for attenders vs nonattenders, respectively), level of postgraduate training, baseline or later tests of knowledge, or patient factors. The postintervention survey revealed marked overestimation by physicians of their personal compliance with NCEP guidelines, although there was strong support for clinic efforts that would screen patients for lipid disorders independent of physician initiative. CONCLUSIONS: This study raises questions about the effectiveness of education alone for improving compliance with NCEP guidelines. The effectiveness and efficiency of timely, individualized feedback should be explored in studies over a longer period. Innovative alternative approaches are suggested by the responses to our survey and other research in preventive practices. PMID- 1456862 TI - Treatment of cryptosporidiosis with paromomycin. A report of five cases. AB - Cryptosporidiosis continues to be one of the most devastating complications of the acquired immunodeficiency syndrome, causing severe, chronic diarrhea that is largely refractory to treatment. More than 60 drugs have been tried in the treatment of cryptosporidiosis, none of which have been consistently successful. We describe the successful treatment of cryptosporidiosis in five patients with acquired immunodeficiency syndrome with oral paromomycin at a dose of 1500 to 2000 mg/d. All five patients had resolution of symptoms and normalization of bowel movements, although one patient later relapsed while receiving paromomycin. Three of five patients cleared Cryptosporidium from the stool. Paromomycin is a promising therapy for cryptosporidiosis in acquired immunodeficiency syndrome and further prospective clinical trials are warranted. PMID- 1456863 TI - Carbamazepine neurotoxic reaction after administration of diltiazem. AB - A patient with epilepsy controlled by carbamazepine developed a carbamazepine neurotoxic reaction after being given an increased dosage of diltiazem hydrochloride as adjunctive therapy. Abrupt withdrawal of diltiazem reduced the circulating carbamazepine concentration and resulted in an epileptic attack. Awareness of the interaction between diltiazem and carbamazepine and careful monitoring of carbamazepine blood levels is recommended to prevent the dangerous neurotoxic effect associated with this combination. PMID- 1456864 TI - The role of skin testing for penicillin allergy. PMID- 1456865 TI - Medical futility: where's the attending? PMID- 1456866 TI - Limited form of systemic sclerosis improved with enalapril. PMID- 1456867 TI - Medical residents and the pharmaceutical industry. PMID- 1456868 TI - SOAP is good for medical record. PMID- 1456869 TI - Why SOAP is good for the medical record?: another view. PMID- 1456870 TI - Keep SOAP, not HOAP, alive. PMID- 1456871 TI - Atherosclerotic lesions. Natural history, risk factors, and topography. AB - This article describes the development of human atherosclerosis as a framework on which to integrate and incorporate the research on thrombosis and hemostasis of participants in the 1992 College of American Pathologists Conference XXII on Hemostasis and Atherosclerotic Disease. Included are the early classic studies of the morphological features of atherosclerosis, atherosclerosis in different populations, the distribution of atherosclerotic lesions among arterial segments, the topography of atherosclerotic lesions within arterial segments, and the relationship of risk factors for coronary heart disease to the arterial lesions of atherosclerosis. Special attention is given to the development of atherosclerosis in young people, including findings from the Pathobiological Determinants of Atherosclerosis in Youth study. The data in this review provide confirmation of the development of atherosclerosis at an early age and relate atherosclerotic lesions to certain coronary heart disease risk factors. Any role of thrombosis or hemostasis in atherosclerosis must be integrated into this framework. PMID- 1456872 TI - Factors controlling smooth-muscle cell proliferation. AB - Injury to the arterial wall normally elicits a rapid and significant increase in smooth-muscle cell (SMC) replication with the subsequent development of intimal lesions. A variety of factors have been proposed to control SMC replication, but recent work has highlighted the role of basic fibroblast growth factor (bFGF) and platelet-derived growth factor in this process. In the carotid artery of the uninjured rat, we have shown that the SMCs express mRNA for bFGF and that bFGF can be readily extracted from these arteries. Following mechanical injury to the artery, ie, after balloon injury, we suggested that bFGF is released from damaged cells and then stimulates adjacent SMCs. In support of this concept, the infusion of a blocking antibody to bFGF was found to significantly inhibit the early SMC replication induced by use of a balloon catheter. The addition of the antibody at the time of injury, however, did not inhibit the development of intimal lesions. In contrast, studies by us and other investigators have shown that platelet derived growth factor is not directly important for SMC replication after balloon injury, but that it plays a key role in stimulating the migration of SMCs into the intima. Intimal SMC replication was not inhibited with antibodies to either bFGF or platelet-derived growth factor. Therefore, while significant inroads have been made in understanding the initial events, we still do not fully understand all the processes involved in the proliferation of arterial intimal lesions. PMID- 1456873 TI - Theories and new horizons in the pathogenesis of atherosclerosis and the mechanisms of clinical effects. AB - In this report, I relate some of the major new concepts of the cellular and humoral pathological changes of atherosclerosis to the many observations that have been made recently in the clinicopathological study of the Pathobiological Determinants of Atherosclerosis in Youth, in some of the more human lesion related animal models, and in epidemiological studies. An effort is made to explain the transition from the many important gross findings to the microscopical, immunohistochemical, and micromorphometric observations that have been made in a number of recent large-scale autopsy studies that are still under way in a number of countries. PMID- 1456874 TI - Cytokines and growth factors in atherogenesis. AB - The development of laboratory techniques for the culturing of vascular endothelial and smooth-muscle cells during the 1970s, followed by the rapid advances in molecular and cell biology during the 1980s, provided the foundation for the identification of growth factor and cytokine networks involved in maintenance of the normal vasculature as well as participating in diverse pathologic processes involving blood vessels. Vascular cells can produce and respond to a vast array of biochemical messengers that control cell replication, differentiation, and many specific cell functions. Investigators are beginning to explore the changes in the patterns of messengers exchanged between the vascular cells and infiltrating leukocytes during the initiation and progression of atherosclerosis. A variety of in vitro and in vivo studies have indicated that growth factors and cytokines that mediate the critical processes of inflammation and wound healing also play a central role in vascular disease. Indeed, many view atherosclerosis as the result of excessive or prolonged chronic inflammation and wound healing in response to diverse injurious stimuli to cells of the vessel wall. Vascular injury may result from many varied and interacting forces, including nutritional and metabolic abnormalities such as hyperlipidemias or elevated homocysteine, mechanical forces associated with hypertension, exogenous toxins including those found in cigarette smoke, abnormally glycated proteins associated with diabetes mellitus, oxidatively modified lipids or proteins, and, possibly, viral infections. Ultimately, a greater understanding of the activated cytokine and growth factor networks within the vascular wall following injury and during atherogenesis will allow clinical scientists to identify steps susceptible to therapeutic intervention using recombinant cytokines, antibodies, soluble receptors, or receptor antagonists. Other therapeutic strategies may involve the transfection of specific genes, which may inhibit atherosclerosis, into vascular cells at sites prone to lesion formation. PMID- 1456875 TI - Hemodynamic forces and vascular cell communication in arteries. AB - As the interface between the blood and the rest of the vessel wall, the endothelium is directly affected by hemodynamic shear stress (frictional) forces that locally regulate vascular tone and are implicated in the localization of atherosclerosis. There are many diverse responses of endothelial cells to hemodynamically related mechanical stresses ranging from ion channel activation to gene regulatory events. The processes of force transmission from the blood to the cell, and force transduction within the endothelium to electrophysiologic, biochemical, and transcriptional responses are poorly understood. This article reviews the principal mechanisms currently thought to be involved and outlines the signal pathways from the endothelium to underlying smooth-muscle cells. PMID- 1456876 TI - Thrombosis and cardiovascular risk in the elderly. AB - Current concepts of cardiovascular disease pathophysiology include a prominent role for thrombosis as a key factor. Thrombosis is not only the usual precipitant to a clinical event, but it may also be involved in atherosclerotic plaque development throughout most of the adult years. However, our understanding of thrombotic risk factors, especially in the elderly, is poor and research has just begun in this area. Fibrinogen has been clearly established as an independent risk factor in the middle aged, but there are conflicting data concerning older persons. Factor VII and plasminogen activator inhibitor-1 look promising as risk factors in the middle aged, but there are no data currently available concerning the status of these factors in the elderly. Many associations exist between the thrombotic risk factors and other cardiovascular risk factors such as plasma lipids and glucose intolerance, making the establishment of independence difficult, and little is known about how these different factors may interact in older individuals. Ongoing studies should provide many answers in the near future. PMID- 1456877 TI - Hemostatic factors and risk of cardiovascular disease in women. An overview. AB - This report presents an overview of epidemiologic and clinical studies on the relationship between plasma levels of hemostatic factors and risk of cardiovascular disease in women. In addition, research on an association between hemostatic factor levels and gender, as well as estrogen status, is briefly reviewed. Only the Framingham Heart Study has published prospective results showing elevated fibrinogen levels to be associated with excess risk of coronary heart disease among women. However, taken together, the evidence to date from epidemiologic and clinical studies suggests potentially important hemostatic effects of aging, gender, and sex hormone levels on risk of cardiovascular disease in women. PMID- 1456878 TI - Hemostasis and cardiovascular risk. The British and European experience. AB - There is evidence that increased reactivity of blood plasma to thrombogenic surfaces (hypercoagulability) may contribute to the risk of thrombotic occlusion of a coronary artery in coronary heart disease. The Northwick Park Heart Study found raised levels of factor VII coagulant (VIIc) activity and fibrinogen in men at high risk of a coronary event. Several other European studies have confirmed the latter finding, but the Northwick Park Heart Study is the only study to report formally on VIIc to date. Plasma VIIc is increased in the presence of hyperlipidemia and on a high fat diet, and falls with lipid-lowering therapy and a reduction in fat intake. Fibrinogen concentration is raised in smokers and decreases when the habit is given up. Thus, these markers of thrombogenic risk are readily controlled by standard preventive measures against coronary heart disease. Unresolved issues include: (1) whether the distinctive features of the Northwick Park VII bioassay improve the value of VIIc as a predictor of coronary heart disease; (2) the separate extent to which activation of factor VII and increases in factor VII concentration account for the raised VIIc in hyperlipidemia; (3) the basis of the raised fibrinogen in men at high coronary heart disease risk, even among nonsmokers; and (4) the usefulness of plasma levels of activation peptides of factors IX, X, and prothrombin as markers of thrombogenic risk. PMID- 1456879 TI - The study of gene-environment interactions that influence thrombosis and fibrinolysis. Genetic variation at the loci for factor VII and plasminogen activator inhibitor-1. AB - We describe studies on variation in the genes coding for factor VII (FVII) and plasminogen activator inhibitor-1 (PAI-1) that influence levels of these proteins in the blood. For FVII, we have identified a genetic polymorphism that results in the substitution of arginine at residue 353 to glutamine. The frequency of the glutamine allele is approximately 0.1 in samples of individuals from the United Kingdom (n = 777) and the United States (n = 140) and in Afro-Caribbeans (n = 49), and is significantly higher in a sample of individuals from the Indian subcontinent (n = 53). In all samples, carriers of the glutamine allele had levels of FVII coagulant activity 20% to 25% lower than those with only the arginine allele. These differences were highly statistically significant in the United Kingdom sample. This effect was consistent in healthy men and women and in those with coronary artery disease. In individuals homozygous for the glutamine allele, both FVII coagulant activity and antigen are low, and the mechanism of the association appears likely to be due to an effect on secretion from the liver or stability in the plasma. In individuals in the general population FVII coagulant activity is positively correlated with levels of plasma triglycerides, due to the effect of such lipoproteins on activation of FVII. This relationship appears weaker in individuals carrying the glutamine allele, and since elevated FVII coagulant antibody is associated with risk of thrombosis, this is an example of how environmental factors may interact with an individual's genotype to determine his or her thrombotic risk. Roughly 20% of the general population are carriers of the glutamine allele and are likely to be genetically protected from such risk. For PAI-1, we have recently shown that variation at the PAI gene locus, detected as DNA polymorphisms, is associated with between-individual differences in levels of PAI-1. We have now detected a common sequence change in the promoter region of the gene that explains part of this effect. The sequence change is at position 675, where a fifth guanine (5G allele) has been inserted into a run of four guanines (4G allele) when compared with published sequences. In a sample of both 83 healthy individuals and 105 young patients with coronary artery disease from Sweden, the frequency of the 4G allele is roughly 0.5, and those individuals homozygous for the 4G allele have higher levels of PAI-1 than those with other genotypes (29% higher). Preliminary data show that the 5G allele binds a hepatic nuclear protein that the 4G allele does not, suggesting that the mechanism of the effect may be due to a direct effect of the sequence change on transcription of the PAI-1 gene.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1456880 TI - The role of the membrane in the expression of the vitamin K-dependent enzymes. AB - The hemostatic response to vascular damage results in the focal generation of thrombin to produce a fibrin/platelet clot at the site of vascular injury. This regulated hemostatic response derives from the assembly and activity of enzyme complexes that are localized to surfaces presented by the vascular damage. The product of each enzymatic complex provides the serine protease component required for the assembly and activity of each successive enzyme complex, ultimately leading to the formation of thrombin. When one limits attention to those complexes clearly associated with hemostatic or thrombotic risk, the significance of the vitamin K-dependent enzyme complexes becomes apparent. Each of these complexes involves a serine protease and a cofactor protein that assemble on a membrane surface in the presence of Ca++. The expression of an active complex involves, in addition to the activation of a zymogen to an enzyme, the presentation or activation of a cofactor protein and the provision of the appropriate membrane to support the reaction. The membrane plays an essential part in the formation and expression of vitamin K-dependent complexes; thus, its regulation is vital in the expression of procoagulant activity. PMID- 1456881 TI - Vascular immunopathology and atheroma development in human allografted organs. AB - Human atherosclerosis requires decades to develop spontaneously, and its development customarily is not monitored by serial biopsies. Atherosclerosis in allografts develops within months, and biopsy specimens are usually obtained from the grafts. We have used immunocytochemical techniques to study biopsy specimens of cardiac and renal allografts for parameters of vascular changes. The antibodies used in this investigation were specific for T lymphocytes, macrophages, IgM, and complement, and detailed studies were done with the use of antibodies specific for components of the hemostatic, fibrinolytic, and natural anticoagulant pathways. The results indicated a lack of association between the appearance of cellular infiltrates and measurable alterations in vascular endothelium and smooth-muscle cells. Although infiltrating macrophages and lymphocytes were identified in biopsy specimens with vascular change, such changes were also observed in biopsy specimens that were devoid of cellular infiltrates. The most prominent vascular changes in endothelium and smooth-muscle cells were accelerated hemostasis, depressed fibrinolysis, and deranged anticoagulant pathways. A negative association between the presence of IgM and fibrin on endothelial cells was also identified. Whether vascular changes are due to immunologically mediated reactions or to as yet undefined metabolic stresses of the graft-host relationship remains to be determined. This study provides a model for the study of vascular changes in atheroma development as viewed through the window of transplant-induced atherosclerosis. PMID- 1456882 TI - Lipid-related clotting reactions of clinical significance. AB - Several lipid-related reactions involving coagulation and fibrinolytic mechanisms have been described. Many of these reactions have been related to the development of atherosclerosis and thromboembolism. In this article, I review the antiphospholipid antibody syndrome, the tissue factor pathway inhibitor, the involvement of fatty acids in fibrinolysis, and the Lp(a) lipoprotein. PMID- 1456883 TI - Measurement of apolipoprotein B-containing lipoproteins for routine clinical laboratory use in cardiovascular disease. AB - Although research studies, using complex methods, have shown apolipoprotein B level to be a better marker for coronary artery disease than cholesterol level, it is unclear whether apolipoprotein B level can perform as well when measured by automated clinical laboratory kit methods. The purpose of this study was to determine whether apolipoprotein B level assayed by a kit method is a better marker for coronary artery disease than low-density lipoprotein and total cholesterol levels in patients presenting for angiography. The subjects were two groups of male patients, 44 to 70 years old: 139 with disease and 41 without. Apolipoprotein B level differentiated more than 20-fold better than total or low density lipoprotein cholesterol levels between the medians of the two groups and showed better diagnostic sensitivity and better diagnostic specificity than total and low-density lipoprotein cholesterol levels. Triglyceride levels were highly significant but showed poorer diagnostic sensitivity than apolipoprotein B level. We conclude that apolipoprotein B level is a more effective marker for coronary artery disease than low-density lipoprotein or total cholesterol levels. PMID- 1456884 TI - Bilateral mucinous cystadenocarcinoma of the testis and epididymis. AB - We describe an intratesticular mucinous cystadenocarcinoma in a 59-year-old man. The tumor was bilateral and appeared in the right testis and the left epididymis. The testicular tumor was a well-demarcated nodule, 3.5 cm in diameter, that extended from the lower testicular pole (close to the albuginea) to the epididymis compressing the corpus and infiltrating the cauda. The contralateral tumor, a 2.5-cm nodule located in the corpus epididymidis, compressed the ductus epididymidis. Both tumors consisted of multiple cavities varying in size, separated from one another by connective tissue septa that were incompletely lined by a columnar pseudostratified epithelium. The epithelial cells immunostained positively for carcinoembryonal antigen and comprised two cell types: cells showing a hyperchromatic nucleus, located in the basal portion of the cell, abundant rough endoplasmic reticulum, apical vacuoles, and numerous microvilli; and mucous cells. The cystic lumen showed a mucous content and sloughed epithelial cells. The differential diagnosis and histogenesis of these tumors is discussed. PMID- 1456885 TI - Acanthamoeba meningoencephalitis in a patient with acquired immunodeficiency syndrome. AB - Several cases of Acanthamoeba encephalitis (ie, granulomatous amebic encephalitis) have been reported in patients with acquired immunodeficiency syndrome from the United States. To our knowledge, none so far has been reported from Europe, and this is the first case of amebic meningoencephalitis due to Acanthamoeba in a patient with acquired immunodeficiency syndrome from Italy. The patient was a 24-year-old, human immunodeficiency virus-positive heterosexual man with a 6-year history of intravenous drug use. He was admitted to the hospital because of severe headache, confusion, nuchal rigidity, jaundice, and ascites. He died 5 days later. At autopsy, the brain showed extensive hemorrhagic necrosis with numerous trophic and cyst forms of Acanthamoeba. The amebas were identified as Acanthamoeba divionensis by the indirect immunofluorescence test. PMID- 1456886 TI - Unusual bilateral renal histiocytosis. Extranodal variant of Rosai-Dorfman disease. AB - A 37-year-old Bangladeshi presented with large bilateral masses involving the hilus of the kidneys. No lymphadenopathy was noted. Nephrectomy was performed. Histopathologically, it revealed a lymphohistiocytic and plasma cell inflammatory tumoral proliferation with characteristic lymphophagocytosis by the S100-positive CD1-negative histiocytes. Extranodal presentation of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) should be entertained in the differential diagnosis of bilateral masses involving the kidneys. PMID- 1456887 TI - Androstenediol regulates systemic resistance against lethal infections in mice. AB - We previously reported that subcutaneous injection of DHEA (5-androsten-3 beta-ol 17-one, dehydroepiandrosterone) protected mice from lethal infection. This included both a lethal herpes virus type 2 encephalitis and a lethal systemic coxsackievirus B4 (CB4) infection. Androstenediol (5-androsten-3 beta-17 beta diol, AED), a metabolic product of DHEA is up to 100 x more effective in regulating systemic resistance against lethal infection with CB 4 than its precursor DHEA. Compared to DHEA, treatment with AED was markedly superior in protecting mice against virus induced myocardiopathy, pancreopathy, and mortality. In addition to its protective effect, AED but not DHEA, induced a 3-4 fold proliferation of the spleen and thymus in virus infected animals; this effect of AED was only seen above a certain threshold dose. Neither steroid, however, has shown any significant direct antiviral effect in vitro; similarly, virus tissues titers in vivo are not affected by the hormones. Additionally, both DHEA and AED protected against a lethal infection with Enterococcus faecalis. These observations demonstrate that the steroid hormones DHEA and AED provide a novel approach for prevention and protection of the host from a variety of infectious diseases. PMID- 1456889 TI - Immunological reactivity of a human immunodeficiency virus type I derived peptide representing a consensus sequence of the GP120 major neutralizing region V3. AB - To reduce the opportunities for human immunodeficiency virus type 1 (HIV-1) to evade vaccine induced immunity, the development of subunit vaccines must focus on the characterization of immunogenic epitopes, which are major targets for the immune system. The most dominant site for elicitation of neutralising immune response is located on the external envelope glycoprotein gp120 within the third variable domain (V3). To overcome virus type specificity of antibodies directed to the V3-domain we designed a 36 amino acids long gp120/V3-consensus peptide (V3 C36) based on published biological data and sequence comparisons of various HIV-1 virus isolates. This peptide contains a conserved core sequence which is suggested to form a surface-exposed beta-turn. This peptide also includes T-cell epitopes defined in mice and humans, an ADCC-epitope and two highly conserved cysteine residues which were oxidized to form a cystine derivate, thus allowing correct peptide folding. In ELISA-tests, this peptide reacts with at least 90% of randomly selected sera of European and African patients infected with HIV-1 and is recognized by three different HIV-1/V3 "type-specific" antisera (MN, RF, IIIB strain). Using this peptide as immunogen in rabbits, antisera could be raised with highly cross-reactive and HIV-1/IIIB strain neutralizing properties. Moreover, HTLV/HIV-1/IIIB specific cytotoxic T-lymphocytes (CTLs) of BALB/c mice infected with a gp120 recombinant vaccinia virus recognized the central 16- and 12-mer peptides of the V3-C36 consensus peptide in cytolytic assays, indicating perfect compatibility of the consensus peptide with the IIIB-primed CTLs. The DNA sequence encoding the V3-consensus loop region might be an important component in newly designed recombinant subunit vaccines. In addition, due to its broad serological reactivity, the V3-consensus peptide might play an important role in special diagnostic purposes. PMID- 1456888 TI - Studies on processing, particle formation, and immunogenicity of the HIV-1 gag gene product: a possible component of a HIV vaccine. AB - Antigens in a particulate conformation were shown to be highly immunogenic in mammals. For this reason, the particle forming capacity of derivatives of the HIV 1 group specific core antigen p55 gag was assayed and compared dependent on various expression systems: recombinant bacteria, vaccinia- and baculoviruses were established encoding the entire core protein p55 either in its authentic sequence or lacking the myristylation consensus signal. Moreover, p55 gag was expressed in combination with the protease (p55-PR) or with the entire polymerase (p55-pol), respectively. Budding of 100-160 nm p55 core particles, resembling immature HIV-virions, was observed in the eucaryotic expression systems only. In comparison to the vaccinia virus driven expression of p55 in mammalian cells, considerably higher yields of particulate core antigen were obtained by infection of Spodoptera frugiperda (Sf9) insect cells with the recombinant Autographa californica nuclear polyhedrosis (AcMNPV) baculovirus. Mutation of the NH2 terminal myristylation signal sequence prevented budding of the immature core particles. Expression of the HIV p55-PR gene construct by recombinant baculovirus resulted in complete processing of the p55 gag precursor molecule in this system. The introduction of an artificial frameshift near the natural frameshift site resulted in constitutive expression of the viral protease and complete processing of p55, both in Escherichia coli and in vaccinia virus infected cells. Interestingly, significant processing of p55 resembling that of HIV infected H9 cells could also be achieved in the vaccinia system by fusing the entire pol gene to the gag gene. Moreover, processing was not found to be dependent on amino terminal myristylation of the gag procursor molecule, which is in contrast to observations with type C and type D retrovirus. However, complete processing of p55 into p24, p17, p9 and p6 abolished particle formation. Purified immature HIV virus like particles were highly immunogenic in rabbits, leading to a strong humoral immune response after immunization. Empty immature p55 gag particles represent a noninfectious and attractive candidate for a basic vaccine component. PMID- 1456890 TI - Accumulation of the 126 kDa protein of tobacco mosaic virus during systemic infection analysed by immunocytochemistry and ELISA. AB - Systemic infection of tobacco with tobacco mosaic virus (TMV) strain WU1, is accompanied by massive accumulation of the virus-coded non-structural 126 kDa protein in X-bodies. The development of X-bodies and the time course of the increase in 126 kDa protein in systemically infected leaves were analyzed by immunocytochemistry and ELISA, respectively, using an antiserum raised against a fusion protein of beta-galactosidase and part of the 126 kDa protein. The ELISA assay developed enabled routine detection of viral 126 kDa (as well as 183 kDa) protein in samples of less than 5 mg of systemically infected leaves. Plants were inoculated by differential temperature treatment, whereafter the accumulation of 126 kDa protein was related to viral multiplication, the development of X-bodies and the formation of symptoms. Both 126 kDa protein and coat protein became detectable between 40 and 66 h after transfer of the plants and increased in parallel up to 200 h. Vein clearing was visible at 66 h, followed by mosaic in the newly developed leaves at 112 h. By electron microscopical analysis small X bodies, weakly labelled with antibodies against the 126 kDa protein, were detected as early as 24 h after transfer. At this stage they were not associated with nuclei. Thereafter, however, X-bodies increased in size and 126 kDa labelling density, and were increasingly often observed attached to nuclei. In emerging leaves that developed mosaic symptoms, X-bodies were associated with nuclei already at an early stage. These observations are consistent with the hypothesis that association of X-bodies with nuclei may lead to symptom induction, when the leaf is invaded by the virus early in its development. PMID- 1456891 TI - Detection of chicken anaemia agent DNA sequences by the polymerase chain reaction. AB - A polymerase chain reaction (PCR) assay was developed for detection of chicken anaemia agent (CAA) DNA. The assay used a single set of 20-base primers complementary to sequences located in the coding regions of the CAA replicative form (RF) DNA genome at positions 485 to 504 and 1048 to 1067. The observed amplification product had the expected size of 583 bp and was confirmed to derive from CAA RF DNA by a unique Hind III restriction enzyme cleavage pattern. The amplified fragment was shown to be specific for CAA RF DNA after chemiluminescence dot blot hybridisation with a digoxigenin-labelled 25-base internal probe. The optimised PCR assay was specific for CAA and highly sensitive, being able to detect a single CAA-infected MDCC-MSB1 cell and at least 100 fg of CAA RF DNA. Preliminary results also showed that the PCR assay can detect CAA DNA in clinical specimens from chicks experimentally infected with CAA. PMID- 1456892 TI - Turnip yellow mosaic virus variants produced from DNA clones encoding their genomes. AB - Full-length dsDNA clones that encode the genomes of two Australian turnip yellow mosaic isolates, TYMV-BL and TYMV-CL have been constructed. These clones were transcribed to give 6.3 kb capped ssRNA which infects Chinese cabbages to give symptoms indistinguishable from those produced by the parental viruses. Extensions of up to 26 nucleotides at the 3' end of the TYMV-BL clone delay infections, but virus particles isolated from these plants 4 weeks after inoculation contain RNA with the original TYMV-BL 3' terminus. A 90 nucleotide long portion of the virion protein gene of TYMV-BL was replaced by a synthetic 90 mer primer with 16 nucleotide changes to decrease the large cytosine content (34 42%) characteristic of tymovirus genomic RNA. No reversion of any of the mutated nucleotides to cytosine occurred during 7 passages in Chinese cabbage. Hybrids between the TYMV-BL and TYMV-CL clones were also constructed, by exchanging various portions of the genome. However, it was not possible to determine definitively which part of the viral genome is responsible for the more severe symptoms caused by TYMV-BL as the hybrids gave intermediate symptoms. PMID- 1456894 TI - Tick-borne encephalitis virus interaction with the target cells. AB - The binding of tick-borne encephalitis virus to porcine kidney embryo cells was studied. Anti-idiotypic antibodies against TBE virus E protein precipitated gp110 kDa which is predicted to be a cellular receptor for TBE virus. PMID- 1456893 TI - Partial DNA cloning and sequencing of a canine parvovirus vaccine strain: application of nucleic acid hybridization to the diagnosis of canine parvovirus disease. AB - The cloning and sequencing of an Eco RI-PstI fragment derived from the replicative form of a canine parvovirus (CPV) vaccine strain are reported. The variability of the 5' end of NS 1 protein gene in the genome is confirmed by comparison with previously determined DNA sequences. A 15 nucleotide deletion was also observed in this vaccine strain. In order to improve CPV diagnosis, radioactively labelled RNA or DNA and biotin labelled DNA obtained by random priming of the recombinant plasmid were used as probes mainly on gut or stool samples from naturally infected dogs. Results of filter hybridization correlated well with histopathological diagnosis of parvovirus infection and with hemagglutination tests performed on dog faeces. We propose that nucleic acid hybridization may be an alternative diagnostic method to ascertain the presence of CPV, especially in frozen samples. PMID- 1456895 TI - Some biological properties of a rhabdovirus isolated from penaeid shrimps. AB - Some of the relevant biological properties of a rhabdovirus isolated from penaeid shrimps (RPS) were examined. The virus replicated in an established fish cell line, epithelioma papulosum cyprini (EPC) which allowed for the development of a quantitative plaque assay protocol. Virus replication was not inhibited by the DNA antagonist, 5-bromo-2'-deoxyuridine (20 micrograms/ml). Virus infectivity was sensitive to 20% ethyl ether, low pH, and to 37 degrees C. The virus showed marked lability to repeated freezing and thawing and storage at -10 degrees C, but was stable at -70 degrees C for several weeks. The virus particle to infectious unit ratio in EPC was found to be 30. PMID- 1456896 TI - Nucleotide sequence comparison of the 3'-terminal regions of severe, mild, and non-papaya infecting strains of papaya ringspot virus. AB - The 3'-terminal 2,561 nucleotide residues of the severe HA strain of papaya ringspot virus (PRSV) was determined. Comparison with the published sequence of the mild strain PRSV HA 5-1 showed that they shared a 99.4% identity in their 3' terminal 2,235 residues. There were ten residues different at the NIb gene, resulting in five amino acid changes, and two residues different in the coat protein gene, resulting in two amino acid changes. The 3'-untranslated regions were identical, but HA contained two more nucleotides (AG) at the 3' extreme. Comparison with the published non-papaya infecting type W strain PRSV-W revealed that they shared a 97.9% identity in their 3'-terminal 2,235 residues. There were 40 nucleotides different in the coding region, which resulted in four amino acid changes in the NIb gene and six in the CP gene, and seven nucleotides different in the 3'-untranslated region. PMID- 1456897 TI - Eosinophils as host cells for HIV-1. AB - Transient expression of HIV-1 p24 antigen was observed in eosinophils acutely infected with the HTLV-IIIB strain of HIV-1. PCR analysis of eosinophils isolated from 18 seropositive individuals showed HIV-1 sequences to be present in 2 subjects. These data suggest that eosinophils may act as host cells for HIV-1. PMID- 1456898 TI - Hepatitis E virus in cultivated cells. PMID- 1456899 TI - Cloning of the thymidylate synthetase gene (thyPIG 3) from the Bacillus subtilis temperate phage IG 3. AB - The thyPIG 3 gene from Bacillus subtilis bacteriophage IG 3 was cloned in the plasmid pHV 33. Two recombinant plasmids, pISL 61 and pISL 62 carrying that gene are effective in transforming to thymine prototrophy both Escherichia coli (by complementation) and B. subtilis (by complementation and recombination). The comparison of cloned fragment containing the thyPIG 3 gene and the thyP 3 gene from phage phi 3 T, by restriction analysis and DNA hybridization, suggests a strong homology between the two. The thyPIG 3 gene was mapped in this study in the central region of the IG 3 genome. PMID- 1456900 TI - Molecular cloning and physical mapping of bovine herpesvirus 4 strain DN 599 and comparison with two American field-isolates. AB - Ninety four percent of the genome of bovine herpesvirus 4 (BHV-4) strain DN 599 was cloned and a physical map was constructed by Southern blot analysis using a library of cloned fragments cleaved with the 3 restriction enzymes (Eco RI, Bam HI, and Hin dIII). The genome length was estimated to be 156.5 kbp +/- 0.7. The genome comprises a region of unique segment (114 kbp) and two flanking segments containing tandem repeats. The size of each repeat was approximately 2.35 kbp and each repeat contained one Eco RI site and two Bam HI sites. We also examined two recent American field-isolates of BHV-4 and compared the Eco RI maps of the two isolates with that of DN 599. We observed the following: (1) insertions or deletions of restriction sites at the periphery of the unique segment; (2) variation in the lengths of junction fragments; (3) variations in the lengths of hypermolar Eco RI fragments containing the repeats; and (4) the Eco RI map of one of the American field-isolates resembles the BHV-4 "Movar type" of Europe. PMID- 1456901 TI - New therapies for shock associated with gram-negative sepsis? PMID- 1456902 TI - The prune belly syndrome. PMID- 1456903 TI - Symptomatic colitis in the anal canal after restorative proctocolectomy. PMID- 1456904 TI - Laparoscopic cholecystectomy for acute cholecystitis. AB - Sixty-eight cases of acute cholecystitis managed by laparoscopic cholecystectomy (LC) are reviewed. Thirty-two patients were admitted up to 10 days after onset of symptoms and 31 were completed by LC. One patient was referred from intensive care with gangrenous acalculus cholecystitis and was completed by LC but required subsequent laparotomy to control a bleeding omental vessel. Five patients were admitted with recurrent attacks of pain and histology confirmed resolving acute cholecystitis. Thirty patients had LC on routine operating lists, having recently had pain within 10 days of admission. Histology confirmed acute cholecystitis or resolving acute cholecystitis in these patients. All were completed by LC. Laparoscopic cholecystectomy is a very effective treatment for acute cholecystitis if complete dissection of anatomy can be performed. PMID- 1456905 TI - Laparoscopy-guided percutaneous cholecystolithotomy: an evolving technique. AB - Gall-bladder conservation therapy has been evolving during the past decade. Popular techniques of conservative therapy are extracorporeal shock wave lithotripsy (ESWL) and medical dissolution therapy. The limitations of these procedures have prompted a search for alternative techniques, particularly in relation to percutaneous stone extraction. The cases of four patients with symptomatic gallstones who underwent percutaneous cholecystolithotomy under laparoscopic guidance are reported. The gall-bladder was punctured with a long needle and the tract dilated so that a nephroscope could be introduced. Three cases required stone fragmentation by an ultrasonic lithotripter before removal. Postoperative recovery was uneventful in all cases. PMID- 1456906 TI - The role of manometry, electromyography and radiology in the assessment of faecal incontinence. AB - The results of laboratory investigations in 156 patients presenting with faecal incontinence are reviewed to see if and how these investigations supplement a careful clinical evaluation, and in particular to see if they help in the practical management of the problem. All patients underwent anal manometry, and in addition 52 underwent anal sphincter electromyography and 27 defaecatory proctography. Anal manometry quantified sphincteric weakness, and proved superior to digital assessment in this regard. Resting and squeeze pressures were less in those with complete than those with partial incontinence but the differences were not statistically significant. The measurements of rectal sensation and compliance were not additionally helpful. Single fibre electromyography provided the best measure of denervation with re-innervation and was abnormal in about 85% of the group studied. Jitter studies were unhelpful. Most patients had some abnormality on defaecatory proctography but clinical significance could not be established. The choice of treatment was made on clinical grounds and was not influenced by these investigations. PMID- 1456907 TI - The role of manometry, electromyography and radiology in the assessment of intractable constipation. AB - An analysis is made of functional studies performed in 96 constipated patients to see how these studies influenced the choice of surgical treatment. All patients underwent anal manometry, and other investigations included colonic transit studies (56), anal sphincter electromyography (42) and defaecatory proctography (34). Additionally nine patients underwent full thickness rectal biopsy. The resting anal canal pressures of the patients studied were lower than controls, and fibre density studies on electromyography were abnormal in half the patients studied suggesting a degree of denervation of the sphincter muscles, which possibly related to chronic straining on the toilet. There was evidence of reduced rectal sensation as shown by an increase in the least perceived volume on balloon distension of the rectum, and in those with megarectum and/or megacolon an increase in maximum tolerated volume. The recto-anal inhibitory reflex was used to screen for adult Hirschsprung's disease, but in one patient the reflex was present despite absence of ganglia on full thickness rectal biopsy indicating the need for biopsy as the definitive diagnostic procedure. Delayed colonic transit using radio opaque markers was a necessary requirement before recommending colectomy, and delayed transit was demonstrated in 34% of the patients studied. Anismus on electromyography was found in 20% of the patients but there was poor correlation with failure of the anorectal angle to widen when bearing down on proctography. The investigations helped in the choice of treatment, but were difficult to interpret. They should be used in severe constipation when surgery is being contemplated. PMID- 1456908 TI - A new technique of ankle arthrodesis. AB - A new technique of ankle arthrodesis is described and the results of 12 consecutive procedures are assessed. The method described employs three cannulated transfixion screws and an anterior approach to the ankle. Eleven of the 12 ankles proceeded to solid fusion. One patient developed a painless fibrous non-union. There were no other significant complications. This simple technique provides good compression and adequate resistance to rotatory and angulatory stresses about the ankle fusion site. PMID- 1456909 TI - Laparoscopic fundoplication: a preliminary report of the technique and postoperative care. AB - The technique of laparoscopic fundoplication and its hospital management are described. Thirty day results in seven patients demonstrate the decreased insult to the patient, early discharge and early return to usual function, similar to that seen in laparoscopic cholecystectomy. PMID- 1456910 TI - Oesophageal atresia: the first survival in the Southern hemisphere. AB - The first known survival in the Southern hemisphere following a corrective operation for oesophageal atresia, is reported. Contrary to previous reports, this survival was in 1948 not in 1949 and the survival occurred in New Zealand not in Australia. PMID- 1456911 TI - Venous occlusion: a rare complication of transvenous cardiac pacing. AB - Venous occlusion is an uncommon complication of transvenous cardiac pacing. Fibrotic occlusion of the right subclavian and innominate veins and stenosis of the left innominate vein, after the insertion of transvenous pacing wire, was corrected surgically with an external iliac vein graft. PMID- 1456912 TI - Torsion of the vermiform appendix: a case report and review of literature. AB - A case of torsion of the vermiform appendix is described. It is a rare cause of an acute abdomen with a clinical presentation that is indistinguishable from acute appendicitis. PMID- 1456913 TI - Duplication of the proximal colon mimicking volvulus: a case report. AB - The case of a 56 year old female with intermittent pain, weight loss, anaemia, and a palpable tympanic abdominal mass is reported. Barium enema showed a very redundant loop of proximal colon, which was thought to have undergone recurrent volvulus. At colonoscopy, the findings seemed normal, but a much shorter length of colon was intubated to the caecum than expected from the barium findings. The duplicated colon was discovered only intra-operatively. This unusual diagnosis should be considered when a barium enema shows a long redundant colon which is not confirmed on colonoscopy. PMID- 1456914 TI - The pigmentary dispersion disorder in USAF aviators. AB - The pigmentary dispersion syndrome (PDS) can have serious ocular consequences. Visual changes due to glaucoma and the treatment required can threaten the high level of visual function necessary in military aviation. We reviewed the records of 50 aviators with PDS who were evaluated at the Aeromedical Consultation Service (formerly the USAF School of Aerospace Medicine) over the past 10 years. At last evaluation, 48 were still qualified to fly. Only two aviators were permanently removed from flying duties due to glaucoma. Initial intraocular pressures, cup-to-disc ratios, and refractions were not statistically correlated with progression to glaucoma, but sample sizes were small. At final evaluation, 20 of the 34 aviators with follow-up had glaucoma and required medication. Thirteen eyes underwent laser trabeculoplasty. With appropriate management, the majority of aviators with PDS were able to safely continue their flying careers. PMID- 1456915 TI - The effects of pyridostigmine bromide on visual performance. AB - The effects of pyridostigmine bromide (PB) on selected visual functions were measured on four healthy aviator candidates. Following a pretreatment day during which baseline measurements were completed, subjects were administered currently recommended doses (30 mg, t.i.d.) of PB for 3 d during which their visual functions were assessed using a repeated measures design. Spatial resolution ability was evaluated with high and low contrast visual acuity charts and contrast sensitivity charts at three luminance levels. Dark adaptation was evaluated by measuring visual thresholds for 40 min after a standardized retinal photopigment bleach. Also, refractive error and several oculomotor functions (lateral phoria, fusional vergence, accommodative amplitude, and pupil size) were measured. On days that the subjects ingested PB, only refractive error and pupil diameter were significantly different, and these only minimally. We conclude that the use of PB at doctrinal doses will not significantly compromise an aviator's visual ability. PMID- 1456916 TI - Visual scene effects on the somatogravic illusion. AB - This study attempted to determine which visual scene cues are most effective in overcoming the somatogravic illusion (SGI), a form of spatial disorientation that occurs when a shift in the resultant gravitoinertial force vector created by a sustained linear acceleration is misinterpreted as a change in pitch or bank attitude. Nine subjects were exposed to a gravitoinertial force shift of -30 degrees in the pitch plane, both with their eyes closed and while viewing computer-generated visual scenes through a wide field-of-view head-mounted display. The scenes depicted acceleration over a shoreline by means of horizon, texture, perspective, and color cues that were presented both in isolation and in various combinations. None of the scenes significantly reduced the magnitude of the SGI relative to the eyes-closed (baseline) pitch illusion, even though the textured scenes produced some linear vection. It remains to be established whether low-cost head-mounted visual displays can reliably reduce the magnitude of the SGI and other spatially disorienting illusions. PMID- 1456918 TI - Comparison of four noninvasive rewarming methods for mild hypothermia. AB - Four noninvasive rewarming techniques for mildly hypothermic subjects were compared. Seven subjects were cooled in a water bath of 15 degrees C for 2 h to an average esophageal temperature (Tes) of 36 degrees C. Thereafter, the subjects were rewarmed by immersion of the body in a water bath of 42 degrees C (Method 1), the body but not the extremities in water of 42 degrees C (Method 2), only the extremities in water of 42 degrees C (Method 3), or spontaneous rewarming in blankets (Method 4). Method 1 showed the highest rewarming rate in Tes (10.1 degrees C/h) and an afterdrop in Tes of 0.18 degrees C. Method 2 showed the same afterdrop, but a lower rewarming rate (7.5 degrees C/h). In Method 3, the heat uptake of the extremities was too low to rewarm the subjects effectively. The afterdrop and rewarming rate were 0.38 degrees C and 0.8 degrees C/h, respectively. Method 4 had the lowest rewarming rate (0.2 degrees C/h), and an afterdrop (0.14 degrees C) which was not significantly lower than that of Method 1 or 2. Therefore, Method 1 is recommended for rewarming mild hypothermic subjects because of its high rewarming rate and small afterdrop. PMID- 1456917 TI - Limited heat transfer between thermal compartments during rewarming in vasoconstricted patients. AB - Thermoregulatory vasoconstriction may serve to separate and limit heat transfer between peripheral and central thermal compartments, in effect providing a thermal buffer for central temperature. We hypothesized that thermoregulatory vasoconstriction would limit heat transfer to the central compartment in patients warmed cutaneously. Hypothermic patients (central temperatures < 35 degrees C) recovering from surgery were randomly assigned to receive forced-air warming (n = 6) or warmed cotton blankets (n = 6). The forced-air warmer delivers approximately 50 W of heat, compared to a heat loss of approximately 50 W with warmed cotton blankets. Despite a significantly greater increase in mean skin surface temperature with forced-air warming, central temperature in the two groups did not significantly differ. All patients vasoconstricted and there was no difference in oxygen consumption between groups. These data confirm that thermoregulatory vasoconstriction limits heat transfer from peripheral to central thermal compartments and impedes skin surface warming of the body core. PMID- 1456919 TI - Decrement in manual arm performance during whole body cooling. AB - Six subjects performed three manual arm tasks: 1) prior to immersion in 8 degrees C water; 2) soon after immersion to the neck, but prior to any decrease in core temperature; and 3) every 15 min until core temperatures decreased 2-4.5 degrees C. The tasks were speed of flexion and extension of the fingers, handgrip strength and manual dexterity. There was no immediate effect of cold immersion; however, all scores decreased significantly after core temperature decreased 0.5 degrees C. Further decrease in core temperature was associated with a progressive impairment of performance, although at a slower rate than during the first 0.5 degrees C decrease. Flexion and extension of the fingers was affected relatively more than handgrip strength or manual dexterity. Decrement in performance is a result of peripheral cooling on sensorimotor function with a probable additional effect of central cooling on cerebral function. PMID- 1456920 TI - Thermogenesis induced by inhibition of shivering during cold exposure in exercise trained rats. AB - The present investigation was conducted to examine the role of nonshivering and shivering thermogenesis caused by cold exposure in exercise-trained rats. Wistar rats were divided into warm-acclimated (WA), exercise-trained (ET) and cold acclimated (CA) groups. The trachea was cannulated and a ventilator was connected under light anesthesia and in the supine position. Shivering, oxygen consumption, colonic temperature, blood glucose, and free-fatty acids were measured at 25 degrees C and then at 0 degrees C room temperatures. D-tubocurarine chloride (curare, 0.04 mg/100 g body weight, ip) was given to inhibit muscular activity. Cold-induced oxygen consumption in the ET and WA groups did not decrease when shivering was inhibited, whereas it increased in the CA. The magnitude just after shivering onset for the ET and CA groups as significantly greater than for the WA group. Colonic temperature at the onset of shivering was significantly higher in the WA group than in the ET and the CA groups. The blood glucose concentration during cold exposure and curarization was elevated in the ET group, and did not change in the CA or WA groups. The present results suggest that endurance training at a thermoneutral environment increases cold-induced thermogenic capacity in rats, which may be attributed to preferential carbohydrate utilization. PMID- 1456921 TI - Heat stress in protective clothing: validation of a computer model and the heat humidity index (HHI). AB - Ability to work while wearing protective clothing is often limited by rising body temperature. Peterson analyzed the combined effects of heat, humidity and workload using the Texas Model of Thermoregulation and suggested that environmental heat load imposed on a person wearing heavy, semipermeable clothing could be predicted using the Heat-Humidity Index (HHI = 0.5 Tdb + 0.5 Twb), where Tdb = dry bulb temperature and Twb = wet bulb temperature. Our study was designed to: 1) test the validity of this computer model; and 2) evaluate the applicability of the HHI to heavily clothed subjects working in a variety of thermal environments. Nine men wearing chemical defense clothing were each studied under eight conditions over the range Tdb = 20 - 40 degrees C, Tbg = Tdb + 5 degrees C, relative humidity = 9-75%, and oxygen uptake = 14-27 ml.kg-1 x min 1. Variables analyzed included tolerance time (TT), rectal temperature (Tre), skin temperature, heart rate (HR), weight loss, sweat rate, evaporation rate, and evaporative efficiency. Experiments were designed to last 30-180 min, and continued until Tre = 39 degrees C except when subjective tolerance limits occurred first (12 of 72 experiments). The observed time to reach Tre = 39 degrees C bracketed the predicted time in the more severe conditions, but the model seriously underestimated heat storage in the milder conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456922 TI - The effects of chronic hypoxia on human auditory system sensitivity. AB - We have examined the effects of prolonged periods of hypoxia produced at high altitudes on the latency of the auditory brain-stem evoked response (ABER) in 9 subjects at around sea level, 3,500 m, and 4,370 m. Following an ascent from 1,300 m to 3,500 m over 24 h, the mean blood O2 saturation fell to 86.5 +/- 1.2% (+/- S.E.M.) and was associated with a mean prolongation of latency of wave V of the ABER of 0.34 +/- 0.10 ms (p = 0.011 two-tailed paired t-test). Using the stimulus-level/response latency relation determined at around sea-level for each subject, this prolongation of wave V corresponded to a mean reduction in sensitivity of 9.1 dB +/- 1.6 dB. Over a period of 72 h, blood O2 saturation improved slightly (mean 88.1% +/- 1.8%) and mean wave V latency returned to control values. A second rapid ascent to 4,370 m reduced blood O2 to below prerecovery levels (82.5% +/- 1.7%), but in this case there were no significant changes in auditory sensitivity (p = 0.79 two-tailed paired t-test). These data show that mild hypoxia results in an initial decrease in auditory sensitivity. However, the recovery of sensitivity with more prolonged exposure suggests that the auditory system can compensate for chronic mild hypoxia. PMID- 1456923 TI - The role of ground level oxygen in the treatment of altitude chamber decompression sickness. AB - Most published reports on the treatment of altitude-induced decompression sickness (DCS) deal exclusively with patients treated with hyperbaric oxygenation. Little information exists on the role of normobaric (ground level) oxygenation as a primary treatment modality for altitude-induced DCS. This study reports the U.S. Air Force experience in the treatment of Type 1 altitude chamber DCS with ground level oxygenation (GLO2) during the period 1 January 1989 to 31 December 1991. Data collected included age, sex, time of symptom development, type of initial treatment, and response to GLO2 administration. There were 221 cases of Type 1 DCS, of which 46 were treated with compression therapy without initial use of GLO2. Of the 175 cases treated with GLO2, 40 failed to resolve and were treated with compression therapy. The remaining 135 cases all resolved with GLO2, obviating the need for HBO therapy. Only 8 patients had a recurrence of symptoms after resolution with GLO2, all of which subsequently resolved with compression therapy. Factors associated with a favorable response to GLO2 are discussed. PMID- 1456924 TI - Myocardial infarction occurring at the conclusion of centrifuge training in a 37 year-old aviator. AB - In September 1988, the U.S. Air Force instituted routine centrifuge training for aircrew involved in high performance, high G aircraft. As of June 1991, 6,078 aircrew members have been trained. This report documents an anterolateral myocardial infarction that occurred in a 37-year-old pilot immediately after his centrifuge training profile. The individual had a history of elevated lipids and smoking, and was on a waiver from the USAF for Flying Class II duties for hyperlipidemia treated with cholestyramine. PMID- 1456925 TI - Ethical concerns in the practice of military aviation medicine. AB - Military aviation physicians are frequently placed in conflicting ethical situations regarding the areas of patient loyalty, confidentiality, and reporting of findings or hazards. The American College of Occupational and Environmental Medicine has developed a set of guidelines for ethical conduct to assist physicians providing occupational health services. This paper attempts to show that these guidelines can be applied similarly by physicians providing aeromedical services. These guidelines can be helpful in resolving ethical dilemmas that can occur in the daily practice of aviation medicine. PMID- 1456926 TI - Recent developments in U.S. Air Force pilot candidate selection and classification. AB - Recent U.S. Air Force policy decisions regarding Specialized Undergraduate Pilot Training (SUPT) have eliminated the need to classify pilot candidates into training specialties prior to entering primary jet training. Under the new system, specialized training assignments will occur at the completion of primary jet training and will be based on flying and academic performance, student preferences, and aircraft availability. Another significant change to the SUPT program was the development of a refined pilot candidate selection model that reduced potential threats to test compromise and gaming strategies. PMID- 1456927 TI - Kelly's hospital ship. AB - The JN-4 "Jennie" and DH-4 air ambulance conversions used by the U.S. Army during the period 1918-1924 are well-known to those interested in the history of air evacuation. However, another "unknown" craft was also used during this period. The author unravels the mystery of this craft converted for use as an air ambulance at Kelly Field, TX. PMID- 1456928 TI - Cases from the aerospace medicine residents' teaching file. Case #52. A flyer with syncope. AB - The clinical presentation, evaluation, and diagnosis of various types of syncope were discussed. The case also demonstrates the aeromedical management and disposition. This case was unique in that the aviator was initially denied a waiver and permanently grounded, but later returned to flying status. PMID- 1456929 TI - Yellow lens effects upon visual acquisition performance. PMID- 1456930 TI - Time course of aggressive arousal in female hamsters and male rats. AB - This study replicates previous reports which show that allowing a female hamster to carry out an attack on a conspecific increases its aggressive arousal, i.e., transiently decreases the latency and increases the probability of an attack on a second trial. We now report that attack priming also occurs in male rats. Interpolating delays of 0, 10, 30, and 90 min between the first and second trials resulted in similar patterns of temporal changes in hamsters and rats. The differences in gender, housing condition, and other factors make the parallel in the time course of aggressive arousal in these two rodent species quite striking. The results rule out a simple model of exponential decay with a short time constant. Carrying out an attack sets in motion a complex set of internal events that affect subsequent aggressive behavior similarly in hamsters and rats. PMID- 1456931 TI - Anterograde and retrograde enhancement of 24-h memory by glucose in elderly humans. AB - The present experiment examined anterograde and retrograde enhancement of memory storage by glucose in elderly humans. Glucose (50 g) or saccharin was administered shortly before or immediately after acquisition of a narrative prose passage. Recall was tested 24 h later. Glucose administration before or after presentation of the material to be learned significantly improved recall 24 h later compared to performance in the saccharin condition. These findings suggest that glucose retroactively enhances memory storage processing in elderly humans and that the enhancement of memory outlasts the transient elevations in blood glucose levels after glucose ingestion. PMID- 1456932 TI - Regulation of rat maternal behavior by broadband pup vocalizations. AB - Pups emit a broadband vocalization ranging from 2 to 40 kHz that generally occurs when the mother sits or steps on her pups. In an earlier study (Ihnat, White, and Barfield, under review), we noted that the mother was more likely to move on the pups and step on them when she was temporarily deafened with ear plugs. This research was extended in the present study by using two different methods to prevent 2-day-old pups from emitting broadband vocalizations. In the first experiment, the female was presented with six of her pups for a 10-min test. In half the tests, the pups had been anesthetized with pentobarbital; in the other half, the pups received saline. In the second experiment, females were presented with pups whose mouths had been sealed with an adhesive substance. In a final study, pups received the adhesive substance on their ventral surface as a control. When the pups were unable to vocalize, there was an increase in the amount of time per bout that the mother spent in incidental contact with her pups; in the sham condition, however, there was no change in her behavior. In addition, the female was less likely to group all her pups within the 10-min duration of the test when the pups could not call. Since pups emit primarily broadband vocalizations in response to handling prior to 4 days of age, broadband calls appear to reduce incidental contact and facilitate retrieval into a group. PMID- 1456933 TI - An ephemeral sex pheromone in the urine of female house mice (Mus domesticus). AB - From previous research, the ultrasonic vocalizations of male mice (Mus domesticus) to female mouse urine were hypothesized to be learned as a result of classical conditioning during adult heterosexual encounters. According to this interpretation, a previously neutral conditioned stimulus in female urine comes to elicit vocalizations as a result of its association with some other unknown unconditioned stimulus associated with adult females. However, the research from which this hypothesis was derived utilized urine collected from females housed in metabolic cages. Three experiments further examined the classical conditioning hypothesis using two types of female urine: (i) metabolic-cage-collected urine and (ii) freshly voided urine. Experiment 1 demonstrated that, in contrast to vocalizations to metabolic-cage-collected urine, adult heterosexual experience was not necessary for males to vocalize to freshly voided female urine. In addition, unlike metabolic-cage-collected urine (Experiment 3), freshly voided urine remained a potent stimulus for eliciting vocalizations during repeated testing (Experiments 2 and 3). Finally, freshly voided urine appeared to cause a previously neutral stimulus (cotton swab) to acquire ultrasound eliciting properties (Experiment 2). We suggest from these findings that two chemosignals that elicit vocalizations from males may exist in female mouse urine: (i) a potent, but volatile or easily degraded, unconditioned stimulus to which males vocalize without sexual experience and (ii) a nonvolatile, chemically stable conditioned stimulus. PMID- 1456934 TI - Those cheating rats: male and female rats use odor trails in a water-escape "working memory" task. AB - Three-month-old Sprague-Dawley rats were trained on a working memory win-stay (spatial delayed matching-to-sample) water-escape task with the escape platform location the same for all subjects on a given trial, a procedure that maximizes the buildup of an odor trail to the escape platform. In subsequent tests during which the location of the escape platform varied randomly between subjects, the rats, especially the females, while continuing to perform above chance level, made increased errors. Varying the platform location between subjects eliminated odor trail as a nonambiguous cue for locating the escape platform. In a second experiment females performed better than males on a reference memory odor trail discrimination task which involved following the path of like-gender "pathmaker" rats to the escape platform. The relatively poor use of odor trails by the males was associated with a high frequency of choosing a preferred choice section or returning to the choice section selected first on the immediately preceding trial (perseveration). Collectively, the two experiments demonstrate that rats can use either working memory or odor trails to locate an escape platform in a water maze, and that they, especially females, will use odor trails in a working memory task if odor trails are available. Clearly, the location of the escape platform should be varied randomly between subjects in tests of working memory. PMID- 1456935 TI - Persistence of chronic nicotine-induced cognitive facilitation. AB - Nicotine has been found in a variety of species and behavioral paradigms to improve memory performance. The beneficial effect of nicotine has been seen after both acute and chronic administration. Interestingly, improved performance has been seen 24 h after acute injection and for at least 2 weeks after chronic administration. However, it is not clear from previous studies whether the persistence of the improved performance represents a true carryover of the drug effect or is due to the behavioral experience while under nicotine's effect. The current study was conducted to determine whether the facilitating effect of nicotine on learning and memory performance could be seen after withdrawal even if there was no behavioral training during the period of chronic nicotine administration. Rats were administered nicotine chronically for 3 weeks but were not tested during that time. Starting 1 week after withdrawal they were trained on a working memory paradigm in an eight-arm radial maze. The nicotine-treated rats started out at control-like levels of performance, but showed significantly faster learning as detected by three different measures of choice accuracy. By the final phase of testing the control subjects had caught up with the nicotine treated rats. After the acquisition phase, acute challenges with the nicotinic and muscarinic antagonists, mecamylamine and scopolamine, did not elicit any differential effects in the nicotine-treated and control groups. The current study demonstrated that nicotine-induced cognitive facilitation persists for at least 4 weeks after withdrawal and does not depend upon behavioral test experience under the influence of the drug. The mechanism for this persisting effect is not currently understood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1456936 TI - Short forms of the "reference-" and "working-memory" Morris water maze for assessing age-related deficits. AB - Short forms of the reference- and working-memory versions of the Morris water maze, each limited to 10 trials, were examined for their reliability and sensitivity to age-related deficits in 16- and 24-month F-344 rats, relative to 2 to 2.5-month young controls. The reference-memory task used long intertrial intervals of 23 h, but required learning only one target location, while the working-memory task used shorter intertrial intervals of 60 min but required learning many different target locations. The reference-memory task was very reliable, revealed large age-related deficits, and correctly identified almost all aged rats as impaired relative to young controls. The working-memory task was less reliable, revealed smaller deficits than the reference memory task at 24 months, and did not discriminate as well between 2.5- and 24-month rats. Furthermore, in the working-memory task 16- and 24-month rats had longer swim paths than 2- to 2.5-month rats on the first trial of each trial pair, which is suggestive of a deficit in processing spatial information and raises questions about the validity of this test as a specific test of working memory. Although the working-memory procedures may be preferable under certain conditions, perhaps as a measure specific to hippocampal dysfunction, the reference-memory task seems more sensitive to age-related deficits and more accurately identifies older rats as impaired. These results are consistent with previous reports that age-related deficits in acquiring spatial learning tasks are common and that the magnitude of the deficit increases as the length of the retention interval increases. PMID- 1456937 TI - Effects of protein malnutrition and the administration of cortisol on the reflexologic development in rats. AB - The use of neurological tests in various states of undernutrition has confirmed the presence of delays in reflex ontogeny. Glucocorticoid administration in conditions of normal nutrition produces diminished growth and alterations in brain development similar to those observed in malnutrition, but there is not enough evidence about its effect on reflex development. In addition, some facts lead us to think that the use of permissive doses of these hormones during gestation could alleviate some of the effects of protein malnutrition on the development of pups. In the present study the ages at which certain reflexes appeared in the offspring of Wistar rats (Rattus norvegicus) fed a 20% (N) or 10% (M) protein diet from a week before conception to the end of lactation were observed. Each dietary group was subdivided into two: mothers receiving a daily injection during gestation either of a 0.9% NaCl (S) solution or of a 0.5 mg/100 g weight hydrocortisone acetate (C) solution. Results showed that the NS group of pups generally presented earlier ages of appearance of the variables under study than the remaining groups. Pups of the NC group presented delays in the age of appearance of reflexes. Finally, protein malnutrition delayed the appearance of reflexes and this effect seemed to be attenuated by treatment with hydrocortisone. Thus, hydrocortisone administration in protein malnutrition conditions seems to be beneficial although the results are harmful when administered under normal nutritional conditions. PMID- 1456938 TI - Strategy selection in a task with spatial and nonspatial components: effects of fimbria-fornix lesions in rats. AB - The main purpose of the present research was to investigate the ability of rats to learn a 12-arm radial maze task that requires the concurrent utilization of both spatial and intramaze cue information. The task involves in a single trial both place and cue learning as well as reference memory (RM) and working memory (WM). Since the animal can choose place and cue arms in any order, the strategies employed to learn the task can be studied as well as the kinds of memory errors that are made. The results of Experiment 1 showed that the number of errors made on the place and cue components of the task did not differ, and that more RM than WM errors were made early during learning. As the task was learned, the animals tended to choose the place arms before choosing the intramaze cue arms, thus suggesting that a spatial strategy was employed first followed by a cue strategy. In Experiment 2 lesions of the fimbria-fornix resulted in temporary impairments in both RM and WM that were especially apparent on the spatial component of the task. The lesioned rats also switched from choosing mostly place arms early during the trial to choosing more cue arms. While fimbria-fornix lesioned rats recovered from the memory impairments with training, the change in response strategy persisted throughout postoperative testing. The procedure of combining both spatial and non-spatial components concurrently in the same task should prove of value in studying response strategies in animals. PMID- 1456939 TI - Role of the cerebellum in spatial orientation in the rat. AB - Adult DA/HAN strain rats were submitted to a spatial orientation task consisting of finding a reward in an open field. They were first submitted to an initial learning session and 10 days later to a retrieval test. The animals were divided into four groups of five rats each: animals that were cerebellectomized before the initial learning session or after the initial learning session, sham-operated rats, and control (intact) animals. Different parameters that characterize the spatiotemporal organization of the rat's exploratory behavior were quantified. From the results, it can be concluded that the cerebellum is not absolutely necessary in the processes that sustain spatial learning but that it is involved in the mechanisms sustaining focused spatial memory and in the cognitive processes of the motor program elaboration and not only in the regulation of the movement being done. PMID- 1456940 TI - The involvement of the hypothalamic preoptic area on the regulation of thirst in the rat. AB - Acute reversible lesion in the medial preoptic area (MPOA) by unilateral injection of the local anesthetic lidocaine chlorhydrate (1 microliter, 20 ng/microliters) causes a transient increase in water intake induced by water deprivation in rats. Since lidocaine suppresses the nervous activity, leaving intact fibers of passage and blood vessels, the results suggest an intrinsic inhibitory action of the MPOA on the regulation of water intake. Drinking elicited a return to volumes similar to those of control rats, 3-4 h after lidocaine administration. Lidocaine released into the lateral preoptic area (LPO) slightly decreased or did not change water intake, as compared with controls. The urinary excretion in the MPO group was higher than that of the controls and the LPO, while this last group excreted significantly less urine. The ablation of the POA with lidocaine suggests that the medial aspect of the POA has an intrinsic inhibitory factor influencing drinking, while the lateral aspect did not show a relevant effect. PMID- 1456941 TI - Effects of aging on the diurnal pattern of water intake in rats. AB - This study was undertaken to confirm previous findings that Long-Evans rats exhibit age-related changes in the diurnal/nocturnal distribution of water intake and to examine the circadian pattern of these age-related changes. Twenty-one aged and 10 young pathogen-free rats were continuously monitored for water consumption over 12:12 h light/dark cycles. ANOVA, profile analysis, and cosinor analysis each demonstrated that aged rats differed from young rats. The age related changes in circadian pattern can be described as a blunted rhythm (decreased amplitude) and an altered timing of peak activity (advanced acrophase). These differences, however, were only apparent in a subset of aged rats with the remaining aged rats exhibiting a circadian pattern indistinguishable from that of the young group. PMID- 1456942 TI - Reversible inactivation of the nucleus of the solitary tract impairs retention performance in an inhibitory avoidance task. AB - Several peripherally acting hormones and drugs are known to modulate memory storage processes, yet the mechanisms which permit these agents to influence memory is not well understood since they do not freely enter the brain. The nucleus of the solitary tract (NTS) is one brainstem structure which receives important neural input from the periphery. Therefore, the objective of this experiment was to determine whether the NTS is involved in modulating processes contributing to memory formation. Male Sprague-Dawley rats were trained in a one trial inhibitory avoidance task (0.35 mA, 0.5 s footshock). Immediately or 2 h after training microinjections of 2% lidocaine hydrochloride (20 mg/kg) or a phosphate buffer solution were administered bilaterally into the NTS. Two other groups received microinjections of lidocaine into the fourth ventricle or cerebellum. On retention tests given 48 h after training the latency to reenter the dark compartment of the apparatus was recorded. The retention latencies of rats receiving bilateral microinjections of 0.5 microliter of lidocaine hydrochloride into the NTS were significantly shorter than those of animals given injections of a buffer solution (0.5 microliter), delayed injections of buffer or lidocaine, or control injections of lidocaine into the cerebellum or fourth ventricle. These findings suggest that memory storage processes are impaired by reversible inactivation of the NTS after training. The implications of these findings in terms of a possible role of the NTS in modulating brain processes involved in memory storage are discussed. PMID- 1456943 TI - An analysis of behavioral plasticity in male Caenorhabditis elegans. AB - Caenorhabditis elegans is a simple soil-dwelling nematode which has two sexes, hermaphrodite and male. The male C. elegans is differentiated from the hermaphrodite by the presence of 14 sensory structures in the tail. In this study, we compared the behavioral responses of males and hermaphrodites to head touch and to tap. We hypothesized that the anatomical difference in sensory structures might result in behavioral differences in the reversal response to vibratory stimulation (a tap to the side of the holding dish). In the response to increasing intensities of tap, both sexes showed an increase in response magnitude, with the males showing larger responses than hermaphrodites. In addition, the male was shown to be capable of simple nonassociative learning: it demonstrated habituation and recovery from habituation in a similar manner as the hermaphrodite. Tail-touch-induced inhibition of the reversal response appeared to be similar in males and hermaphrodites. The evidence suggests that the touch withdrawal circuit in hermaphrodites is also present in the male C. elegans, and that the subtle differences in response to tap seen in males may result from the additional sensory receptors of the copulatory bursa of the tail. It seems clear from these studies that these structures do not play a key role in the male worm's response to tap. PMID- 1456944 TI - Reinstatement of latent inhibition following a reminder treatment in a conditioned taste aversion paradigm. AB - Reminder treatments have been shown to facilitate the retrieval of a variety of conditioned responses. Whether or not similar results would occur with an experimental paradigm which involves primarily memory for a stimulus, i.e., where no particular response is specified, is unclear. Accordingly, using Sprague Dawley rats, we employed a latent inhibition paradigm with a long (10 days) retention interval between sucrose (CS) preexposure and sucrose-illness pairing (training). The results demonstrated a loss of latent inhibition following the 10 day retention interval suggesting "forgetting" of the CS preexposure. However, placing a single reminder exposure to the CS within the preexposure-to-training interval reinstated the preexposure effect. Controls indicated that in the absence of the initial preexposure the reminder per se did not produce latent inhibition. Thus, a reminder can reinstate a stimulus attribute (flavor representation) and explicit conditioned responses. PMID- 1456945 TI - Conditioned taste aversions support drug discrimination learning at low dosages of morphine. AB - The present experiment shows that a conditioned taste aversion procedure can support discrimination learning at dosages of morphine comparable to those required to produce motivational effects. Sprague-Dawley rats were injected with 4.0 mg/kg morphine sulfate prior to a saccharin-lithium chloride pairing, and physiological saline prior to a saccharin-saline pairing. The rats avoided the saccharin solution following the administration of morphine and consumed significantly more saccharin following saline administration after four discrimination cycles. After this initial discrimination the subjects were trained with progressively lower doses of morphine. Discrimination learning was apparent at doses of 2.0, 1.5, 1.0, 0.75 and 0.5 mg/kg. Animals initially trained with 1.0 mg/kg morphine also learned the discrimination but required 10 training cycles. After this initial discrimination the subjects were trained with progressively lower dosages of morphine and showed a discrimination at a dosage of 0.5 mg/kg. PMID- 1456946 TI - Hepatic accumulation of alpha-aminoisobutyrate in the pregnant rat at term. AB - In vivo measurements of the tissue accumulation of alpha-amino[1-14C] isobutyrate ([1-14C] AIB) clearly indicate that the hepatic accumulation of the amino acid is not increased in the fed late pregnant rat. Starvation induced an increases in the hepatic AIB accumulation both in virgin and late pregnant animals, thus suggesting that AIB accumulation by the liver is dependent on food intake. The results suggest that amino acids are similarly directed to the conceptus and the liver during late gestation in the rat. PMID- 1456947 TI - Glycogen metabolism during human liver development. AB - Development of enzymes of glycogen metabolism in human fetal and neonatal liver was investigated. Glycogen was present in quantitatable amount from early gestational age onwards; however, ultrastructurally it could not be detected earlier than 20 weeks. Increase in glycogen synthetase a activity during 21-36 weeks of gestation subsequently resulted in glycogen accumulation. A rapid degradation of this glycogen storage, at birth, was accompanied by an elevation in glycogen phosphorylase a activity. The present investigation to be the first to provide a complete profile of glycogen storage and differentiation of glycogen metabolising enzymes in preparing the prenatal fetus for its independent nutritional life. PMID- 1456948 TI - Post-transcriptional control of H3 histone variants synthesis. AB - In cultured HeLa cells the rates of H3.1 and H3.2 synthesis measured by pulse labeling experiments reflect the steady state content of the two histone variants. This pattern, however, is largely modified when histone translation is carried out in vitro on RNA isolated from the same cell line. In vivo, H3.1 and H3.2 are synthesized approximately at the same rates while the product of H3 mRNA translation in vitro is mostly represented by H3.1 histones. Factors which have so far been invoked for the control of histone messenger RNA stability and translation efficiency are not sufficient to explain our data which in addition indicate that histone H3.1 and H3.2 have different roles in the organization of the genetic material. PMID- 1456949 TI - Improved production and purification of interferon-alpha-4a using a T7 RNA polymerase expression system. AB - An improved method for the synthesis and purification of human interferon-alpha 4a is presented. Interferon-alpha-4a was prepared using a T7 RNA polymerase expression system, where it was expressed from the vector pET-3a. Biologically active interferon-alpha-4a was isolated from the E. coli cells and purified using protamine sulphate precipitation, anion-exchange chromatography and affinity chromatography utilising a monoclonal antibody specific for human interferons alpha. PMID- 1456950 TI - Enhancing potency of liposomal monensin on ricin cytotoxicity in mouse macrophage tumor cells. AB - Monensin, a carboxylic ionophore, which is known to disrupt intracellular trafficking of proteins was intercalated in liposomes and its effect on the stability of liposomes and cytotoxicities of ricin and Pseudomonas exotoxin A in mouse macrophage tumor cells J774A.1 was studied. Stability of liposomes containing monensin was comparable to liposomes without monensin. The cytotoxicity of ricin and Pseudomonas exotoxin A was significantly enhanced by 1nM liposomal monensin (15.7 and 3.6 fold respectively). The enhancing potency of monensin in neutral and negative vesicles was found to be similar, while it was drastically reduced in positive vesicles. The specific uptake of 125I-gelonin from neutral and negative vesicles was not significantly different, whereas from positive vesicles no uptake was observed. Serum strongly influenced the binding at 4 degrees C of positive vesicles as well as the enhancing potency of monensin in these vesicles. Monensin in neutral and negative vesicles significantly reduced the lag period of ricin action, while in positive vesicles, it had no effect. These studies clearly indicate that liposomes could be used as a delivery vehicle for monensin. PMID- 1456951 TI - Studies on the entrapment and stability of liposomes containing sulfatide from human brain. AB - Reverse-phase evaporation vesicles containing cerebroside sulfate (sulfatide) from human brain were prepared and their stability and efficiency for entrapment of bovine serum albumin were studied. It has been found that increasing the content of sulfatide from 0 to 15 mol% in the vesicles increases the encapsulation for bovine serum albumin by 0.7- to 3.1-fold, depending on the ratio of solvent:buffer used during liposome preparation. The presence of sulfatide also enhances the stability of the liposomes. Our results suggest that the ability of sulfatide to increase the captured volume and to bring charges to membrane surface may be responsible for the increased protein encapsulation and stability of the sulfatide-containing reverse-phase evaporation vesicles. PMID- 1456952 TI - Structure-activity relationship for ETB agonism in truncated endothelin-1 analogs. AB - The essential part of the ETB-selective agonist N-acetyl GluAlaValTyrPheAlaHisLeuAspIleIleTrp (N-Ac-4AlaET-1(10-21)) for ETB agonism was studied by single amino acid replacement. Single L-alanine substitutions at positions 14, 17, 20 and 21 and the corresponding D-amino acid substitutions at positions 14 and 16-21 resulted in remarkable decreases in ETB binding activity. Furthermore, these analogs elicited endothelium-dependent vasorelaxation in parallel with ETB binding activity. These data indicate that the amino acid residues of Phe14, Leu17, Ile20 and Trp21 and the backbone structure at Phe14 and His16-Trp21 in ET-1 are important for ETB agonism. PMID- 1456953 TI - EDTA induces differentiation and suppresses proliferation of promyelocytic leukemia cell line HL-60--possible participation of zinc. AB - Effects of ethylenediaminetetraacetic acid (EDTA), a chelator of divalent cations, on the proliferation and differentiation of human promyelocytic leukemia cell line HL-60 were examined. Incubation of HL-60 cells with 200 microM of EDTA suppressed cell proliferation, and induced differentiation assessed by reductivity of nitro blue tetrazolium and activity of alpha-naphthyl butyrate esterase. These effects were inhibited by zinc (Zn) dose-dependently at concentrations of up to 20 microM, but not by other divalent cations including Ca, Mg, Fe, Cu, Ni, or Cd. Although addition of 200 microM EDTA for 24 hr decreased the c-myc mRNA level of HL-60 cells, coaddition of 20 microM of Zn also reversed this effect on c-myc mRNA level. Treatment with EDTA did not change the half-life time of degradation of c-myc mRNA after addition of actinomycin D (5 micrograms/ml). These findings suggest that Zn deficiency suppresses c-myc gene transcription which is followed by suppression of proliferation and induction of differentiation of HL-60 cells. PMID- 1456954 TI - Reduction of nitrofuran compounds by heart lipoamide dehydrogenase: role of flavin and the reactive disulfide groups. AB - In order to elucidate the mechanism of the biological activation of nitrofurans, the interaction of these compounds with lipoamide dehydrogenase (LipDH)** was investigated. LipDH catalysed one-electron reduction of several nitrofuran derivatives. The reaction could be demonstrated spectroscopically and was enhanced by cadmium, arsenite and anaerobiosis. The role of flavin in the nitroreductase activity was supported by (a) the nitrofuran effect on the spectral properties of anaerobic, arsenite-inhibited, NADH-reduced LipDH; (b) FAD catalytic activity in a NADH-nitrofuran model system; and (c) the nitroreductase activity of LipDH monomer. Two-electron nitrofuran reduction to less oxidized products was inhibited by cadmium, arsenite and NAD+. The possible role of reactive nitrosofuran derivatives as intermediates of the nitrofuran reduction sequence was supported by the LipDH capability for catalysing 2-nitroso-1 naphthol redox-cycling. The nitroso naphthol reduction was inhibited by cadmium and arsenite, like the two-electron nitrofuran reduction. PMID- 1456955 TI - Heparin stimulates the collagen synthesis in mineralized cultures of the osteoblast-like cell line, MC3T3-E1. AB - We found that heparin induced an increase in collagen synthesis in MC3T3-E1 cells cultured for 15 and 30 days. Northern blots showed that the effect of heparin on the collagen synthesis was mediated through the mRNA expression of type I collagen (day 15). Although heparin stimulated collagen synthesis over and above that stimulated by the transforming growth factor (TGF)-beta, heparin did not stimulate TGF-beta binding. This study indicates that heparin has special tasks both in bone formation and resorption, since it has the ability to form and degrade collagen. We suggest that heparin assists the regulation of collagen metabolism at bone resorption sites. PMID- 1456956 TI - One-step purification of E. coli elongation factor Tu. AB - The tuf A gene, encoding the E. coli elongation factor Tu, was cloned in the pGEX gene fusion system. Upon expression EF-Tu is fused to glutathione-S-transferase serving as a purification handle with affinity for glutathione immobilised on agarose. This allows purification of EF-Tu in a one-step procedure. The construct was designed in order to make possible the release of authentic EF-Tu by cleaving the fusion protein with the protease factor Xa. PMID- 1456957 TI - Hoarseness can signal throat cancer. PMID- 1456958 TI - Professional practices perspective on ... caseloads in schools. PMID- 1456959 TI - Drug abuse in pregnancy. PMID- 1456960 TI - ASHA standards upheld by Medicaid services in WV. PMID- 1456961 TI - 1992 Medicare payments. PMID- 1456962 TI - Why now? Changing school speech-language service delivery. PMID- 1456963 TI - Challenges of education reform. PMID- 1456964 TI - Curriculum-based collaboration. What is changing? PMID- 1456965 TI - The place for assistive technology. PMID- 1456966 TI - A model program: meet it in St. Louis. PMID- 1456967 TI - Support personnel. PMID- 1456968 TI - Empower and collaborate! PMID- 1456969 TI - Relay centers. PMID- 1456970 TI - A possible silent majority? PMID- 1456971 TI - Augmentative communication coursework needed. PMID- 1456972 TI - Bloom, Menyuk, Philips, Williams receive ASHA honors. PMID- 1456973 TI - Educational outcomes of babies compared. PMID- 1456974 TI - Speech-language pathologists: key players. PMID- 1456976 TI - The dream ... an accessible America. The hopes ... the fears. PMID- 1456975 TI - What's the message? John Hancock called to task. PMID- 1456977 TI - The dream ... an accessible America. Let's do it right. PMID- 1456978 TI - The dream ... an accessible America. McMilestone--McMenus. PMID- 1456979 TI - The dream ... an accessible America. Challenge for the clinician. PMID- 1456980 TI - The dream ... an accessible America. A bright and shining moment. PMID- 1456981 TI - Assistive listening systems: how ASHA members fit in. PMID- 1456982 TI - Making an international airport communication accessible. PMID- 1456983 TI - Nationwide relay services. PMID- 1456984 TI - Americans with Disabilities Act and you. PMID- 1456985 TI - Picture this--TriAlliance video. PMID- 1456986 TI - The dream ... an accessible America. Interpreting services. PMID- 1456987 TI - What do you know? What do you need to know? AB - This article is meant to serve as a general overview of the ADA and the regulatory areas that have the greatest implications for audiologists and speech language pathologists. If you would like more detailed information, copies of the regulations and technical assistance are available from federal agencies (See Table 1) and through federally funded ADA technical assistance grants (See Professional Practices Perspective). Now it's time for a retest on the quiz. PMID- 1456988 TI - Speech-language pathologists in the schools. AB - This data page profiles speech-language pathologists working in school facilities. Of particular interest is an examination of differences between those employed in preschools versus other school facilities. Andrea K. Blake is coordinator of ASHA's research division. PMID- 1456989 TI - Medicare home health program target of national investigation. PMID- 1456990 TI - (Not) for women audiologists only. PMID- 1456991 TI - Semantics and PCP marketing in audiological practice. PMID- 1456992 TI - Audiometrists. To be or not to be. PMID- 1456993 TI - Clinical education in audiology. Style and status. PMID- 1456995 TI - Kudos to consumer corner. PMID- 1456994 TI - Ear infections and the Marlboro Man. PMID- 1456996 TI - Need for mentoring. PMID- 1456997 TI - Professional education in audiology. Survey of California audiologists. PMID- 1456998 TI - Caseloads of audiologists. PMID- 1456999 TI - How to rid yourself of stuttering in under 60 seconds. PMID- 1457000 TI - Employment rights of people with communication disabilities. PMID- 1457001 TI - Standards for professional service programs in audiology and speech-language pathology. AB - In the June/July 1991 issue of Asha, the Council on Professional Standards published for comment proposed revisions of the standards for American Speech Language-Hearing Association (ASHA) Professional Services Board (PSB) accreditation. The council considered all of the comments received, made appropriate revisions, and took final action on the revised standards, which will become effective on January 1, 1994. The new standards and implementation statements related to each standard are provided in the following sections. The Standards represent requirements that must be met by all applicants. Implementation Statements are designed to interpret and supplement the standards by providing examples, referencing relevant policy or guideline statements, or specifying types of data or other documentation relevant to a specific standard. The implementation statements were developed by the PSB and have been reviewed by the Council on Professional Standards. PMID- 1457002 TI - Women and audiology. PMID- 1457003 TI - Coexistence of communication disorders in schoolchildren. PMID- 1457004 TI - [Changes in auriculoventricular conduction due to the effect of ethanol]. AB - Transcoronary ablation of atrioventricular conduction by dehydrated alcohol was attempted in one patient with refractory ectopic atrial tachycardia. Ethanol (1.5 ml) was delivered after selective catheterization of the atrioventricular nodal artery in a patient in whom the artery could be identified by cineangiography. The mean creatine kinase (MB fraction) at four hour to six hour after ablation was 40 U. No electrocardiographic QRS changes was seen. The procedure was successful. The patient is asymptomatic 3 months after procedure. Transcoronary alcohol ablation of atrioventricular conduction should be considered in patients in whom electrical techniques have been unsuccessful. PMID- 1457006 TI - [Observation on malaria transmission intensity at a stone-pit of the mountain area in Baoan County, Guangdong Province]. AB - Zhangshubu stone-pit in Baoan County is located in the mountain area. The workers' camps are 2-3 km away from the village. In a recent survey, in malaria peak season (June, July, August) An. anthropophagus accounted for 87.7% (1059/1207) of the total anopheline population and the average man-biting rate was 10.90, 24.88 and 8.71 respectively. The sporozoite positive rate, the human blood index and the daily survival rate were 0.54% (3/554), 1.0 and 0.803 respectively. The parasitaemia rate, the rate of gametocyte carriers, and the rate of persons with malaria history within 1-2 months were 45.5% (10/22), 13.6% (3/22) and 50.0% (11/22), respectively. On average, the entomological inoculation rate A, B and C calculated by three methods were 0.084, 0.665 and 0.215, respectively, indicating that the workers might get malaria infection if they stayed at the camp for 1.5-11.9 days. An analysis of the malaria onset time of the patients suggested that the time calculated from the inoculation rate A was closer to the real situation than those calculated from the inoculation rate B or C. The prevalence trend of malaria could be predicted through the monitoring of the entomological inoculation rate. PMID- 1457005 TI - The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19 kDa and Bcl-2 proteins. AB - Cooperation between the adenovirus E1A and E1B oncogenes is required for transformation of primary quiescent rodent cells. Although expression of E1A alone will stimulate cell proliferation sufficient to initiate transformed focus formation, proliferation fails to be sustained and foci degenerate. Coexpression of either the 19-kDa or 55-kDa E1B oncoproteins with E1A permits high-frequency transformation by overcoming this cytotoxic response. Without E1B 19-kDa protein expression, however, transformants remain susceptible to induction of cell death. Rapid loss of viability is coincident with nucleolytic cleavage of DNA in intranucleosomal regions and chromatin condensation, hallmarks of programmed cell death (apoptosis). Furthermore, overexpression of a known suppressor of apoptosis, the Bcl-2 protooncogene, can rescue E1A-induced focus degeneration. Thus E1A-dependent stimulation of cell proliferation is accompanied by apoptosis and thereby insufficient to singly induce transformation. High-frequency transformation requires a second function encoded by the E1B 19-kDa protein to block apoptosis. PMID- 1457007 TI - [Characteristics of tobacco smoking in schools in Andorra]. AB - 1600 schoolchildren aged 13 to 18 answered an anonimus, self administered questionnaire, in a cross sectional study to estimate the prevalence of cigarette smoking in the high grades schools in Andorra. 46.6% answered they did smoke cigarettes, either daily (11.2%) or occasionally (35.4%). Ten per cent of actual smokers did already smoke at age 10, and 50% at age 13. More girls (48.8%) than boys (44.4%) smoked (p less than 0.05) but boys smoked a greater number of cigarettes (p less than 0.001). Ninety five percent smoked Virginia tobacco, and little more than 50% used filter tipped cigarettes. Two thirds of smokers inhaled the smoke of cigarettes; this was more common among daily smokers. Again two thirds of smokers answered they would be prepared to quit smoking. 31% of those who had tried smoking said they believed they would smoke in the future, while only 5.6% of those that never smoked previously said so (p less than 0.001). Actual smokers answered they believed that they would not smoke in the future much less often than non smokers. Parents let boys smoke more than girls when the children started doing so, particularly before age thirteen and after age fifteen. These are the first available data about the community studied describing some features of its cigarette smoking habit. Their knowledge may well help to plan disease protection and health promotion developments addressed to youngsters in Andorra. PMID- 1457009 TI - Stressful events not linked to onset of AIDS symptoms in HIV-positive men, U-M reports. PMID- 1457008 TI - Intracranial arterial aneurysm due to birth trauma. Case report. AB - The authors present what is believed to be the first description of an intracranial arterial aneurysm attributable to birth trauma. A male neonate, the product of a precipitious, instrumented, footling breech delivery, exhibited seizures at the age of 18 hours. A computerized tomography scan of the head showed hemorrhage along the tentorium with a globular component at the incisura. Transfontanel Doppler ultrasound examination detected pulsatile arterial flow within the globular mass. Cerebral angiography demonstrated a 1.5-cm saccular aneurysm arising from a small distal branch of the superior cerebellar artery. The pathogenesis of aneurysms in children is obscure and controversial. Birth trauma may be responsible for some pediatric aneurysms that are currently classified as idiopathic or congenital, particularly aneurysms in the region of the tentorial incisura. PMID- 1457010 TI - Survival response of a human glioma cell line to hyperthermia associated with rhein. AB - The effect of association of hyperthermia with the anti-inflammatory drug rhein (RH), 4,5-dihydroxyanthraquinone-2-carboxylic acid, on the clonogenic activity of human glioma cells has been examined. RH inhibits neoplastic growth mainly through an ATP depletion, but thermal cell killing is not mediated by the drug induced changes in the energy status of the cell. The analysis of the interaction between RH and hyperthermia, performed with the isobolar method, demonstrates an additivity of the response so that the effectiveness of the combined treatment is the result of two independent effects. Although the effect of this combination is purely additive, RH allows us to achieve a pre-established cell killing with exposure times at 42 degrees C, which is generally accepted to be clinically achievable. RH might, therefore, be employed to reduce the side effects of hyperthermia without impairing its therapeutic effectiveness. PMID- 1457011 TI - Early-retirement incentive programs for medical school faculty. AB - The Association of American Medical Colleges surveyed the principal business officers of all 126 accredited U.S. medical schools in late 1991 in order to learn about their retirement benefit programs for faculty and whether early retirement incentive programs were being used. A total of 115 of the schools provided usable responses, which the author reports for all schools, public schools, and private schools. For all schools, defined-contribution plans (based on employer's and employee's contributions plus investment earnings) were the preferred type of retirement benefit program (77%, or 89, of the responding schools). Defined-benefit plans (based on a formula that uses variables of age at retirement, years of service, and salary) were available at 37% (43) of the schools. Early-retirement incentive programs had been used by 70% of the responding schools in the five-year period 1987-1991. Sixteen schools provided descriptions of their formal early-retirement programs, which are summarized. The author observes that, although nearly three-fourths of the responding schools are familiar with the use of the incentive programs, these programs have resulted in few actual early retirements. He discusses why this may be true and compares the pros and cons of formal and ad hoc programs. He concludes that no single program can be considered best; each institution must work with its faculty to design programs to meet institutional goals and faculty interests. PMID- 1457012 TI - The crisis in osteopathic medicine. AB - During the last 30 years the osteopathic profession has undergone a remarkable transformation from osteopathy, characterized by manipulative therapy, to osteopathic medicine, characterized by full-service health care, and in the process it has won acceptance from the government, the military, and physicians. These changes in status have resulted in new problems for the profession, because D.O. graduates are turning increasingly toward M.D. programs for residency training, and osteopathic medicine's primary care orientation is being replaced by an emphasis on specialty training. The authors advocate that osteopathic medicine return to its original mission of primary care, abandon specialty training or restrict it to those who have completed primary care residencies, abolish its separate-but-equal posture, and establish lines of communication with allopathic medicine and the American Medical Association to facilitate the development of a rational national policy for primary care that considers the potential osteopathy has to offer in meeting the nation's primary care needs. PMID- 1457014 TI - Dangers in the evaluation of instructional media. PMID- 1457013 TI - South Dakota's third-year program of integrated clerkships in ambulatory-care settings. PMID- 1457015 TI - PlanAlyzer, an interactive computer-assisted program to teach clinical problem solving in diagnosing anemia and coronary artery disease. PMID- 1457016 TI - The future of research at the Department of Veterans Affairs. PMID- 1457017 TI - Journal supplements, libraries, and the FDA. PMID- 1457018 TI - Developing a curriculum on bedside diagnostic and therapeutic procedures. PMID- 1457019 TI - A different perception of teaching ethics in residencies. PMID- 1457020 TI - Relationship of medical students' admission interview scores to their dean's letter ratings. AB - The authors examined the relationship between the admission interview scores for 62 students in the 1986 entering class at Dartmouth Medical School and the students' dean's letter ratings given four years later; they found the relationship to be significant (V = .372, p = .014) and the interview scores to be better independent predictors of the ratings than were total Medical College Admission Test scores or science grade-point averages. Among the 17 students receiving "strong" admission interview scores, 53% received dean's letter ratings in the top one-third and 47% received ratings in the lower two-thirds. Of those 34 who received "medium" interview scores, 68% received ratings in the lower two thirds; all 11 students who received "weak" interview scores received ratings in the lower two-thirds. The authors suggest (1) that admission interview scores help schools to identify more clearly those applicants most likely to become strong, competitive performers in residency and (2) that the significant relationship between interview scores and dean's letter ratings indicates a need to discover what qualities the interview actually measures and to consider the methods by which interviewers are trained, rather than to forsake the interview. PMID- 1457021 TI - The role of grades in gaining admission to highly selective medical schools. AB - The authors examine the role of grades in the admission decisions at a group of 19 highly selective medical schools by analyzing over 8,000 applications from Cornell University students for the entering medical school classes of 1982 through 1989. The results illustrate the great influence of the grade-point average (GPA) on the admission decision. Between the GPA levels of 3.0 and 3.8, the chance of acceptance increased by a factor of about two for each increment of .2 in the GPA. For a subset of the nine most selective of the 19 institutions, the chance of acceptance increased by a factor of five for each increment of .2. At these nine schools, of 1,157 applications with a GPA of less than 3.4, only four were approved. The authors suggest the evidence indicates that students often receive encouragement to continue the application process even though the chances of eventual acceptance are negligible. PMID- 1457022 TI - Multiple authorship in two English-language journals in radiation oncology. AB - Multiple authorship is the listing of more than one person as author of an article in the scholarly literature. Editors, researchers, and others in science publishing have raised concerns about the increasing number of authors being listed per article, the practice of "honorary authorship" (listing as an author someone who made little or no contribution to the work being reported), and the danger of the dilution of responsibility when many authors are involved. The authors studied multiauthorship in the two most popular English-language journals on radiation oncology, examining 1,908 papers and letters published in the International Journal of Radiation Oncology, Biology, and Physics (IJROBP) and Radiotherapy and Oncology (RO) from 1983 through 1987. There was no increase in the number of authors per article during this period, when the median number for IJROBP was four and that for RO was three. The number of authors varied by type of article, by country (France had the largest median number, six for IJROBP and five for RO), and by the authors' institution. The first author's gender was unrelated to the number of subsequent authors for an article. The proportion of men first authors varied widely between countries and institutions. Possible explanations for these variations include the multidisciplinary nature and complexity of some forms of research, institutional policies concerning the use of authorship as a commodity of exchange, and social-cultural factors. PMID- 1457023 TI - Consistency between peer reviewers for a clinical specialty journal. AB - To analyze the consistency between independent peer reviewers in evaluating and ranking unsolicited articles, the authors used paired reviews of 422 unsolicited submissions to the Journal of Clinical Anesthesia from the end of 1988 through 1991. (The editors of this journal base their publication decisions, to a substantial degree, on congruence of their reviewers' recommendations). The reviewers were chosen for their interest in reviewing and areas of expertise. Their recommendations were ranged along a continuum of four categories: (1) accept outright, (2) accept with revision, (3) reject in present form (article could be revised and submitted again as a new submission), and (4) reject outright. The pairs of peer reviewers were consonant for 169 papers (40%), differed by one category for 168 papers (40%), differed by two categories for 73 papers (17%), and differed by three categories for 12 papers (3%). Thus, most articles' reviews were in consonance or close to it; articles reviewed by two members of the editorial board, however, were significantly less likely to be consonant (32%) than were those reviewed by two nonmembers (44%, chi-square, p = .027). PMID- 1457024 TI - Comparing the accuracies of entire-group and subgroup models to predict NBME-I scores for medical school applicants. AB - To address the question of whether prediction models for subgroups of medical school applicants lead to more accurate predictions of performance than does one model for an entire group of applicants, the authors used data from two groups of students at Jefferson Medical College: 415 students who entered Jefferson in 1985 and 1986, and 396 who entered in 1987 and 1988. Both groups were divided into two subgroups by gender and two subgroups by age. Data from the first group were used to develop prediction models based on the entire group and on its four subgroups. The predictors were undergraduate grade-point averages and Medical College Admission Test scores; the criterion measures were scores on the National Board of Medical Examiners Part I examinations. The prediction models were then applied to data from the second group and its four subgroups: differences in the validity coefficients (.40 to .56) and residual scores (7.2 to 17.9) were not considered to be of practical importance. Hence, the authors suggest that gender and age do not contribute to a prediction bias and that an entire-group prediction model can be used without serious concern for over-or underestimating the predicted scores. PMID- 1457025 TI - Attitudes of part-time community internal medicine faculty about their teaching. AB - The authors sent a six-item questionnaire regarding attitudes about teaching to 130 part-time community internal medicine faculty at the University of Illinois College of Medicine at Rockford in August 1991; of the 90 (69%) who responded, 53 were salaried and 37 nonsalaried. Substantial numbers of the salaried faculty responded (1) that teaching is important for their career development (25, 48%), compared with nine (22%) of the nonsalaried faculty, and (2) that they expected to increase their commitments to the medical school (50, 75%), compared with 24 (65%) of the nonsalaried faculty. Of all the faculty, fewer than the authors expected--22 (24%)--felt that their teaching interfered with their clinical practices. As expected, most (76, 84%) responded that salary was necessary. The authors suggest that their results may be helpful to other medical schools, because with the setting of medical education changing from the hospital to the community, the importance of part-time faculty is increasing. PMID- 1457026 TI - Effect of clerkship timing on third-year medical students' grades and NBME scores in an obstetrics-gynecology clerkship. PMID- 1457027 TI - Relationship of interviewer and applicant variables to admission interview ratings of medical school matriculants and nonmatriculants. PMID- 1457028 TI - Retention of surgical knowledge by senior medical students. PMID- 1457029 TI - Medical students' decisions to report classmates impaired by alcohol or other drug abuse. PMID- 1457030 TI - Effectiveness of an inpatient-based rheumatology elective. PMID- 1457031 TI - Occurrence, removal and seasonal variation of "thermophilic" campylobacters in a sewage treatment plant in Italy. AB - Monitoring of "thermophilic" campylobacters in a sewage treatment plant in Bologna (Italy) has shown that incoming sewage contained a most probable number of 1630 campylobacters/100 ml. The secondary treatment in activated sludge tanks reduced 98.61% of campylobacters, 95.32% of fecal coliforms, 96.46% of fecal streptococci, 93.36% of salmonellas and 93.01% and 88.29% of BOD5 and COD respectively. Subsequent tertiary treatment with 3 ppm of chlorine dioxide for 15 min reduced 100% of campylobacters and salmonellas. Significant correlation coefficients were found in incoming sewage between campylobacters and salmonellas (p < 0.01) and between campylobacters and fecal coliforms (p < 0.02). Campylobacter jejuni and Campylobacter coli constituted 51.3% and 48.7% respectively of the 80 strains isolated. In incoming sewage 66% of the strains isolated were found to be Campylobacter jejuni whereas Campylobacter coli strains were prevalent in activated sludge effluent (69.7%). The greatest frequency of isolation and the higher counts were obtained during the Spring to Summer period with distinct peaks in May, June and July. This seasonability is probably due to the seasonal variation of campylobacter infections in man and animals. PMID- 1457032 TI - [Development and monitoring of the hygienic water quality at bathing facilities in northwest Germany from 1989 to 1991]. AB - Since the introduction and strict application of EC guidelines on the monitoring of bathing waters began in Lower Saxony in 1989, it has been possible for the first time to reach a comprehensive evaluation of the water quality on the North Sea coast and in the rivers and lakes of this state. The 7648 samples which were analysed in this period produced the most favourable results on the East Friesian Islands, followed by the vast majority of the mainland bathing resorts and some lakes. On the lower stretches of the River Weser and in a few lakes levels were registered at times which exceeded the limits to such an extent that bathing was impossible. In 1991 extreme germination of total coliform bacteria was observed for the first time, presumably due to eutrophic conditions in combination with high water temperatures. PMID- 1457033 TI - [Comparative study of the detection of E. coli after time in seawater with partially modified standard media]. AB - Fecal coliform bacteria (E. coli) are the most important parameter when monitoring the hygienic quality of bathing water according to EC guidelines. Among other things the number of E. coli is clearly dependent on the length of exposure of the bacteria to marine water as well as the media used to establish the number. In a seven-day salt water stress experiment the best rate of recultivation was achieved on average with DEV lactose peptone broth. The Brila MUG medium produced a slightly lower rate of recultivation and the fluorocult lauryl-sulfate-broth the lowest rate of recultivation. After a shorter exposure of bacteria to marine water conditions (up to 24 h) the DEV-lactose-broth produced slightly lower rates of recultivation. An alteration of the standard components of the media did not lead to an improvement in the rate of recultivation. PMID- 1457034 TI - Faecal micro-organisms on the hands of carriers: Escherichia coli as model for Salmonella. AB - To evaluate the public health hazard caused by Salmonella carriers as food handlers, a study was carried out to gather more quantitative data about faecal contamination of hands after stools. Faecal E. coli was used as a model bacterium for Salmonella. In total 92 subjects cooperated in this study. The hand was sampled before toilet use, and also after stools, with or without washing of the hands. Besides E. coli the number of Enterobacteriaceae was also determined. It appeared that hands may be contaminated with Enterobacteriaceae, regardless of toilet use, for a well before as after stools about 60% of the sampled hands carried a detectable number of Enterobacteriaceae. That is why the presence of Enterobacteriaceae on hands is not a good indicator for toilet hygiene. In 4% of the samples before stools and in 25% of the samples taken after stools E. coli could be detected (> 20 CFU/sample). The average 10log CFU of E. coli in the positive samples taken before and after stools were about the same: 2.30 per sample. Hand washing after stools reduced the numbers of Enterobacteriaceae and E. coli on the hands. It was concluded that symptomless Salmonella excretors in the period starting two weeks after infection form only a low risk in carrying over Salmonella by their hands to food. Especially if normal hygiene is practiced like washing hands after stools, the number of contaminated hands will be very low and furthermore the number of faecal micro-organisms will be very small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457035 TI - [The determination of the discrepancy between the mathematically ascertained and experimentally provable efficiency of UV facilities for water disinfection]. AB - Using three UV-plants of different technical designs for water disinfection, we studied the conformity between experimental germ reduction using standard test organisms and calculated UV-doses under various water flow conditions. Taking into consideration the style of construction of the UV-plants, the irradiation area and the layer thickness were used as constant parameters for dose calculations. This was also employed for the irradiation intensity, since the experiments were performed for a relatively short period compared of the life span of the UV-irradiators. Both exposure time and water transmission were employed as variable parameters in the dose calculations and experimental procedures respectively. The calculated UV-dose and experimentally obtained germ reduction values were comparatively the same for two of the three UV-plants studied. However, no correlation was observed between the reduction of E. coli and the corresponding calculated UV-dose values. Therefore, the calculated UV dose values for any given UV-plant should be considered to be relative and by no means absolute values. We are of the opinion that within a certain range of water flow rate and transmission, antimicrobial effectiveness of different UV-plants should be demonstrated independent of dose values, technical and other construction characteristics. The applicability of the UV-plants studied is discussed. PMID- 1457036 TI - [RoTrac capillary pore membranes for laboratory filtration. II. Bacteria-free filtration]. AB - Because of their special characteristics Capillary pore membranes (CPM) are now applied in several branches of separation techniques and analytics. Besides applications in particle analytics and microfiltration of different media capillary pore membranes can be used in microorganism separation. It was shown that RoTrac CPM can be used for bacteria free (or so called sterile) filtration. Acceptable fluxes were reached in separation of Pseudomonas diminuta (test species ATCC 19146). Membranes with pore diameters of 0.2 micron and smaller always assure a bacteria free filtrate even for a very high bacteria count of about 10(7)-10(8) bacteria/ml. In filtration of Mycoplasma arginini no sterile filtrate was obtained for a pore diameter of 0.08 micron and a high bacteria count of 3 * 10(7) bacteria/ml. The bacteria rejection by a factor of 10(5) was however remarkable. Only for 0.05 and 0.08 micron with reduced bacteria load the filtrate was bacteria free. PMID- 1457037 TI - [Case study of a Legionella epidemic in a rehabilitation clinic]. AB - A series of nosocomial Legionella infections in a rehabilitation center is reported. In a three months period a total of 10 pneumonias with 3 deaths occurred (8 patients, 1 companion, 1 staff member). Serologic analysis proved additional Legionella infections within the nursing staff. The warm-water system was proved to be the source of infection by isolating Legionella pneumophila serogroup 1 subtype Pontiac both in warm-water and patients samples. The air conditioning system could not be ruled out as another (secondary) route of exposure because of shortcomings in construction. Conclusions about prevention and the course of the disease are discussed and standards for warm-water and air conditioning systems are proposed. PMID- 1457038 TI - [The development of an enzyme immunoassay for the detection of the herbicide metolachlor in water samples]. AB - Since December 1990, strict limits for pesticide content in drinking water have been in effect in the FRG. These limits have to be enforced and controlled regularly. Because the classical analytical methods, like GC/MS and HPLC are relatively expensive and complicated, concentration and clean up of the samples are necessary. Therefore, the significance of Enzyme Immunosorbent Assays has increased in environmental analysis. The topics of our research are synthesis of suitable Metolachlor conjugates for immunization and as coating antigen, as well as development of an Enzyme Immunosorbent Assay. The chloroacetanilide Metolachlor was coupled with an AMSA-Spacer on Sheep IgG and with AHT-Spacer on BSA. The epitope density was measured photometrically with TNB-derivate. Polyclonal antibodies were produced in white New Zealand rabbits. Metolachlor AMSA-Sheep IgG conjugate was served as immunogen. The test is indirect and competitive. Microtiter plates are coated with the coating antigen (Metolachlor AHT-BSA conjugate). In the next step the Metolachlor sample competes with the coating antigen for the antibodies. Detection of bounded antibodies is indirect with a peroxidase-labelled secondary antibody. The chromogenic substrates ABTS, TMB and OPD were tested. TMB showed the best qualities, fast turnover, as well as good and steady colour. Titer of serum and crossreactivity of other chloroacetanilide pesticides and their metabolites were tested. With the exception of Alachlor and Dimethachlor, no pesticide showed a high interaction with serum. Quantitative interpretation was done with the logit/log transformation, which allows comparison of different sera and test series. The antibodies are specific but the affinity is not good enough to detect the limits assigned by the "deutsche Trinkwasserverordnung". Raising the concentration, as is done in classical analytical methods, would solve the problems so that the test can be used as a screening test. PMID- 1457039 TI - [Emission measurements of fibrous dust in the Federal Republic of Germany. Fibrous emissions from brake linings of motor vehicles]. AB - The brake and clutch linings of automobiles contain 10 to 70% of asbestos, mainly chrysotile. They are therefore considered to be a significant source of carcinogenic asbestos fibers in ambient air. This could be confirmed by measurements done in urban ambient air in different parts of West Germany. Asbestos fiber concentrations till 1000 fibers/m3 (for fibers longer than 5 microns) were found. It could be also shown, that materials used in the brake lining production as well as dust emitted during car braking contained asbestos fibers with high carcinogenic potency. PMID- 1457040 TI - The effect of progestins on prolactin receptor gene transcription in human breast cancer cells. AB - The sex steroid hormone progesterone modulates the developmental and lactogenic activity of prolactin in the mammary gland. Regulation of the level of prolactin receptor (PRLR) provides one possible mechanism by which this may occur, prompting this investigation of the molecular mechanisms involved in progestin regulation of prolactin receptor levels. Treatment of T-47D and MCF-7 human breast cancer cells with 10 nM of the synthetic progestin ORG 2058 for 24 hr resulted in an increase in all four PRLR mRNA transcripts detected. The effect of ORG 2058 was shown in T-47D cells to be time- and concentration-dependent and resulted in an approximate two-fold increase in PRLR mRNA after 24 hr of treatment with 10 nM or 100 nM ORG 2058. Nuclear run-on assays indicated that ORG 2058 increased the rate of T-47D PRLR gene transcription at all times between 1 hr and 28 hr of treatment. The protein synthesis inhibitors cycloheximide and puromycin abrogated the induction of PRLR gene transcription at 1 hr and 2 hr, which demonstrated that on-going protein synthesis was required for the ORG 2058 effect and suggested that progestins may exert some transcriptional effects via the induction of an intermediary protein. These experiments demonstrated that progestin induced a transcriptionally based increase in PRLR gene expression and provided a mechanism by which progesterone may modulate the mitogenic activity of prolactin during mammary gland development. PMID- 1457041 TI - Complete human NF1 cDNA sequence: two alternatively spliced mRNAs and absence of expression in a neuroblastoma line. AB - Neurofibromatosis type 1 (NF1) is caused by mutations in a large gene on chromosome 17q11.2. Previously described partial cDNAs for this gene predicted a protein related to yeast IRA1/IRA2 and the mammalian RAS GTPase activator protein GAP. To initiate a detailed study of the role of this gene in NF1, we have characterized a set of overlapping cDNAs that represent its complete coding sequence. Our results show that two differentially expressed human NF1 mRNAs differ by a 63-bp insertion in the GAP-related domain. These mRNAs predict two 2,818- and 2,839-amino acid proteins with calculated molecular masses of approximately 317 and 319 kD. Extensive similarity to IRA proteins is evident in a 1,450-amino-acid central segment, roughly between amino acids 900 and 2,350. However, the remainder of the NF1 protein is not significantly similar to other proteins. Interestingly, the SK-N-SH human neuroblastoma line expresses no detectable NF1 mRNA, indicating that expression of NF1 is not essential for viability of this neural crest-derived tumor cell line. PMID- 1457042 TI - Genomic organization of the mouse OSF-1 gene. AB - The mouse OSF-1 protein (also known as pleiotrophin, HB-GAM, HBGF-8, or HBNF) gene was isolated from a mouse genomic library and sequenced. OSF-1 is a 15-kD secreted protein specifically expressed in bone and brain, and is believed to play a role in brain development and osteogenesis. The mouse OSF-1 gene consists of at least 5 exons and 4 introns and spans > 32 kb. Computer analysis of approximately 4 kb of 5'-flanking sequence of the OSF-1 gene revealed two candidate promoter regions. One candidate promoter contains a thyroid hormone/retinoic acid-responsive element and the other contains two glucocorticoid-responsive elements. DNA sequence analysis of novel OSF-1 cDNA clones indicates that two promoters can be utilized in MC3T3-E1 osteoblastic cells. The overall organization of the mouse OSF-1 gene is similar and the locations of the three exon-intron junctions within the coding region are identical to the mouse gene encoding the differentiation-related factor midkine (MK). Based on this similarity and on the high degree of nucleotide sequence homology (approximately 55%) of mouse OSF-1 and mouse MK, we conclude that OSF-1 and MK are generated from a common ancestral gene and are members of a family of structurally and probably functionally related proteins. PMID- 1457043 TI - The HXY box regulatory element modulates expression of the murine IA antigen associated invariant chain in L fibroblasts. AB - The murine invariant chain (Ii) gene has been shown to be interferon-gamma (IFN gamma)-inducible in a number of nonlymphoid cell types. In mouse L cells, steady state levels of Ii mRNA are barely detectable in untreated cells but increase sharply upon IFN-gamma treatment. In IFN-gamma treated L cells, transcription starts 23, 28, 38, and 40 bases downstream of the TATA box. To identify cis acting elements regulating expression of the Ii gene, reporter plasmids containing deletions of the Ii promoter have been constructed and transfected into mouse L cells. Deletion of the H box results in a 50-100% increase in basal expression. Deletion of both the H and X boxes increases basal expression by 200 300% above that seen in constructs containing all three elements. A 25% decrease in basal level expression is seen for constructs that lack the Y-box element when compared to constructs containing the Y-box element but not the H- and X-box elements. DNase I footprinting analysis demonstrates protection of the H, X, and Y boxes as well as a nonconserved region between the H and X boxes. Mobility shift experiments detect a factor specifically interacting with the Y box. Although the H-, X-, and Y-box elements interact with nuclear protein and are regulatory elements in L cells, these elements do not appear to play a role in IFN-gamma induction suggesting that other regulatory mechanisms must account for IFN-gamma's induction of the Ii in L cells. PMID- 1457044 TI - Characterization of liver-enriched proteins binding to a developmentally demethylated site flanking the avian apoVLDLII gene. AB - Although the avian apoVLDLII gene is normally expressed exclusively in the liver of the laying hen, the gene can be activated by estrogen in birds of either sex beginning between days 7-9 of embryogenesis. Developmentally programmed demethylation of sites in the 5'- and 3'-flanking regions of the gene have been shown to occur during this period of embryogenesis, suggesting that they may reflect changes in protein-DNA interactions that are involved in the acquisition of competence to activate the apoVLDLII gene. We have detected specific protein interactions at one location approximately 2.6 kb upstream from the apoVLDLII gene, that includes an Msp I site whose methylation status changes between days 7 and 9 of embryogenesis. The sequence of this region bears significant similarity to binding sites of members of the bZIP family of liver-enriched or -specific factors such as C/EBP, DBP, and LAP, that are characteristically produced relatively late during liver development. In the studies described here, we demonstrate that proteins binding to the upstream apoVLDLII site do not correspond to previously identified liver-enriched or -specific factors. They also display a pattern of activity during development and in human and avian hepatoma cell lines indicating that their expression is increased in proliferating cells. Southwestern blotting and UV cross-linking studies indicate that two proteins of approximately 60 kD are capable of binding to the site and we describe the purification of these factors from crude nuclear protein extracts obtained from rooster liver. PMID- 1457045 TI - Identification and characterization of additional members of the cytochrome P450 multigene family CYP52 of Candida tropicalis. AB - Using different DNA probes from the first two previously described alkane inducible cytochrome P450 genes of the Candida tropicalis CYP52 gene family, we isolated five independent additional members by screening a genomic library under low-stringency conditions. These genes are not allelic variants and, when taken gogether, constitute the largest gene family known in this organism. The seven members of this gene family are located on four different chromosomes and four of them are tandemly arranged on the C. tropicalis genome. The products of the seven genes, alk1 to alk7, were compared to each other and revealed a high degree of divergence: the two most diverged proteins exhibit a sequence identity of only 32%. Six of the seven genes were shown to be induced by a variety of different aliphatic carbon sources but repressed when the organism was grown on glucose. Three of the five additional CYP52 genes could be successfully expressed in Saccharomyces cerevisiae and display different substrate specificities in in vitro assays with model substrates: alk2 and alk3 exhibit a strong preference for hexadecane, while alk4 and alk5 preferentially hydroxylate lauric acid. PMID- 1457046 TI - The first human genes for tRNA(ArgICG), tRNA(GlyUCC), and tRNA(ThrIGU) and more tRNA(Val) pseudogenes: expression and pre-tRNA maturation in HeLa cell-free extracts. AB - A functional tRNA(Val) gene, which codes for the major tRNA(ValIAC) isoacceptor species, and three new tRNA(Val) pseudogenes have been isolated from human genomic DNA. Two tRNA(Val) pseudogenes and a tRNA(Val) variant gene were found to be associated with tRNA genes encoding tRNA(ArgICG), tRNA(GlyUCC), and tRNA(ThrIGU), respectively, on distinct DNA fragments. All tRNA genes, including the pseudogenes, are actively transcribed in HeLa nuclear extract. Pre-tRNAs of tRNA(Val), tRNA(Arg), tRNA(Thr), and tRNA(Gly) genes are correctly processed to mature-sized tRNAs, whereas the three tRNA(Val) pseudogenes yield stable pre tRNAs in vitro. These findings reveal that, together with the three known pseudogenes, half of the members of the human tRNA(Val) gene family are pseudogenes, all of which are active in homologous nuclear extracts in vitro and presumably also in vivo. PMID- 1457047 TI - Rapid isolation of flanking genomic DNA using biotin-RAGE, a variation of single sided polymerase chain reaction. AB - A method is described for quickly and reproducibly isolating genomic DNA contiguous with known DNA sequence by means of the polymerase chain reaction (PCR). Flanking genomic DNA is isolated using a biotinylated sequence-specific primer in combination with a generic hybrid primer that binds to a deoxyoligonucleotide sequence artificially added to the ends of the genomic DNA. Amplified sequences that include the biotinylated primer are purified from nonbiotinylated amplification products by binding to a solid-phase streptavidin matrix. The biotinylated amplification product(s) are subjected to a further round of amplification, after which they can be subcloned and analyzed. This technique was applied to the isolation of three intron-exon junctions. Verification of the identify of these junction sequences was accomplished by designing primers based on the intron sequences isolated by Biotin-RAGE, amplifying across the exon using these intron primers, and sequencing the PCR generated product. PMID- 1457048 TI - Immobilization of aminoacylase from Aspergillus oryzae on synthetic modified polyacrylamides. AB - A series of acrylamide-bisacrylamide copolymers modified by the Mannich Reaction was prepared. The immobilization of aminoacylase from Aspergillus oryzae on the copolymers was studied. All the polymers adsorbed the enzyme and the activity of the immobilized enzyme dependent on the amine used, viz. secondary amine, diamine, or aniline derivative. However, the activity was also influenced by the degree of crosslinking of the polymer. The surface morphology of the dimethylamine-modified polymer, with varying degrees of crosslinking, was analyzed by scanning electron microscope; the polymers having the largest pore diameter possessed the highest enzyme activity. One of the best polymers (DMA A9B8) was used for immobilization of aminoacylase and its properties were studied. It had high enzymatic activity and good operational stability, i.e., retaining 90% of its original activity after being used for 42 days. The use of these copolymers for the preparation of immobilized enzymes is discussed. PMID- 1457049 TI - Preparative in vitro synthesis of bioactive human interleukin-2 in a continuous flow translation system. AB - Recombinant human interleukin-2 has been synthesized in vitro in a continuous flow translation system based on the wheat germ extract. In the course of translation of mRNA the interleukin-2 becomes aggregated due to the adsorption of this protein onto the ribonucleoprotein complex. This process correlates with the cessation of translation that is usually observed in 25-30 min. This can be prevented by the use of a flow system that allows continuous removal of the synthesized protein and maintains a steady concentration of all the necessary components. This approach permitted a yield of 1,500 protein molecules per mRNA molecule. The interleukin obtained promotes the proliferation of the interleukin 2-dependent CTLL-2 cell line. The biological activity of interleukin-2 not subjected to oxidative refolding was 10(5) units per milligram of protein. PMID- 1457050 TI - Interactions of bioactive lipopeptides, iturin A and surfactin from Bacillus subtilis. AB - The antifungal activity of iturin A and its interaction with erythrocyte membranes were enhanced in the presence of surfactin. The modification of the properties of iturin A was explained by the formation of mixed iturin A-surfactin micelles. Such mixed micelles were easily generated when both lipopeptides were in aqueous solutions in the absence of mineral salts but the formation of these micelles did not occur when the solutions contained a high molarity of mineral cations. PMID- 1457051 TI - Use of helper-free retroviral vector to direct a high expression of porcine growth hormone in mouse fibroblast cells. AB - A retroviral vector has been employed to express the cDNA coding for porcine growth hormone (pGH) in the mouse fibroblast cell NIH 3T3 in large quantity. In this study, a single gene vector which contained no selectable marker was used. We have coinfected NIH 3T3 cells with pGH retrovirus and Neo(r) retrovirus to obtain a stable, high-expression clone. Using a superinfection strategy, we further increased the copy number of proviral DNA in the host chromosome, thus increasing the pGH secretion from 22 to 55 micrograms/10(6) cells/24 h. The recombinant pGH produced from mouse fibroblast cells was heterogeneous at the N terminus, which mimicked the situation with bovine growth hormone either from natural sources or from recombinant products derived from mouse fibroblasts. This technology is useful for many biologically important genes to be stably transduced by retroviral vector into mammalian cells and highly expressed. PMID- 1457052 TI - Red blood cells as an antigen-delivery system. AB - The use of adjuvants is usually required to induce strong immunological responses to protein antigens. However, in many cases these adjuvants cannot be extensively applied in human and veterinary vaccinations because of associated inflammatory reactions or granuloma formation. We show here that protein antigens (bovine serum albumin, hog liver uricase, and yeast hexokinase), coupled to autologous red blood cells by way of a biotin-avidin-biotin bridge, elicit an immunological response in mice similar to or higher than that obtained by the use of Freund's adjuvant. Quantities as low as 0.5 micrograms/mouse are high enough to generate these immunological responses. Furthermore, splenocytes of mice immunized by red blood cell-coupled antigens can be used to generate hybridomas secreting monoclonal antibodies. Thus, the delivery of antigens by autologous red blood cells is an effective way to avoid the use of adjuvants for producing anti peptide antibodies and possibly to generate peptide vaccines. PMID- 1457053 TI - Biochemical and rheodynamic properties of red blood cells crosslinked with glutaraldehyde. AB - New data on the properties of red blood cells (RBC) cross-linked with glutaraldehyde are presented (see also Biochem. Biophys. Res. Commun., 1988, 156, 970-977). Equilibrium and kinetic data show that by carrying out the fixation procedure in the absence of oxygen but in the presence of allosteric effectors (e.g., stabilizing the low-affinity (T) quaternary state of hemoglobin), it is possible to maintain, at least in part, the biochemical functions of the crosslinked hemoglobin inside the cell. Moreover, we show that the oxygen affinity of fixed red blood cells (RBC) is still modulated, even though to a smaller degree, by the allosteric effector bezafibrate (BZF), which is able to cross the fixed RBC membrane. Membrane filtration experiments indicate that the higher rigidity of fixed RBC alters significantly their rheodynamic properties and show that in order to exploit "engineered" RBC as "blood substitutes," more flexible cross-linking reagents may offer significant advantages. PMID- 1457054 TI - The effect of early enucleation on the orbit in animals and humans. AB - Facial asymmetry and cosmetic deformity can occur following enucleation. The effect of enucleation on the growth of the orbit can be demonstrated in the rabbit and cat by early enucleation, X-ray study and dry skull measurements. In 42 human patients the anophthalmic orbital changes are determined by roentgenograms. The influencing factors of age and the use of implants are discussed as to changes in the rim, orbital walls and volume, and optic foramina measurements. Growth retardation due to roentgen ray therapy and other clinical aspects are considered which would influence the appropriate clinical management. PMID- 1457055 TI - Temporalis muscle transfer in the treatment of the severely contracted socket. AB - The treatment of severely contracted sockets represents one of the most difficult situations in ophthalmic plastic and reconstructive surgery. In particular, the treatment of the postirradiated socket has been considered "hopeless surgery." In recent years a modified approach to this problem has been tried, in which the use of the temporalis muscle provided a well-vascularized bed for delayed reconstructions. PMID- 1457056 TI - Dermis-fat orbital implantation and complex socket deformities. AB - Autogenous dermis-fat grafts implanted within the orbit survive best, with little loss of volume, when they are placed within Tenon's capsule immediately following the removal of the globe; when the rectus muscles (and anterior ciliary arteries) are anastomosed to the dermal edge of the graft; when no cautery has been applied to the recipient bed; and when the anterior diameter of the graft is no larger than 22 mm. Primary grafting in patients without systemic vascular disease is more effective than secondary procedures, performed on patients with fibrotic, compromised recipient beds and without direct apposition of the rectus muscles to the graft. PMID- 1457058 TI - An operation for the removal of the eye-ball, together with the entire conjunctival sac and lid margins. PMID- 1457057 TI - The role of flaps in the management of contracted eye sockets. AB - Based on the pathology of the eye socket and periorbital deficiencies, three distinct classes of patients can be recognized: I. Those who solely have eye socket deficiency with normal orbital and periorbital tissue. The suggested surgical treatment for this class of patient would be a skin or mucosa graft. II. Patients who have inadequate lining, as well as orbital volume deficiency. The preferred reconstructive approach includes cartilage (rib or ear) with or without fat graft, and skin or mucosa grafts for eye socket expansion. III. For failed reconstructions of classes I and II or for patients with severe orbital and periorbital deficiencies, the choice is one of three flaps: If the superficial temporal vessels and the postauricular skin is intact, the ideal flap is postauricular fasciocutaneous. If the postauricular skin has previously been used yet the superficial vasculature is intact, a secondary flap is the better choice. In cases where both postauricular skin and superficial temporal vessels have been sacrificed the recommended flap is a free flap with microvascular anastomosis. PMID- 1457059 TI - Indications and surgical techniques for orbital exenteration. AB - Indications for the mutilating operation of exenteration are enumerated. They usually involve a malignant neoplasm of the orbital contents, primary, direct extension, or adnexal tissue that cannot be controlled by simple excision or irradiation. Surgically, subtotal exenteration with partial preservation of lids and even conjunctiva may be achieved occasionally. However, total exenteration may be lifesaving. Techniques and precautions are discussed. Advantages and disadvantages of skin grafting that influence the post-operative care are noted. PMID- 1457060 TI - Radical orbital resections. AB - The authors describe the techniques for subtotal, total and radical orbital exenteration. The aspects of primary and late reconstructive surgery are also discussed, with special reference to Frezzotti's personal technique for temporalis muscle transplantation after subtotal exenteration. PMID- 1457061 TI - Frontalis muscle transfer in the reconstruction of the exenterated orbit. AB - A technique using the frontalis muscle to reconstruct the exenterated orbit is described. The technique is simple and does not leave a depression in the temporalis fossa. PMID- 1457062 TI - The history and development of facial prostheses. AB - This paper includes the historical development of the modern-day facial prosthesis, the various materials used from the early days to the present, and the historical input of various people and their contributions towards the development of the qualities in fabricating a lifelike facial prosthesis. PMID- 1457063 TI - Three dimensional imaging and computer-designed prostheses in the evaluation and management of orbitocranial deformities. AB - Three dimensional images reconstructed from two dimensional CT scans allow improved analysis of complex orbitocranial bony deformities. This evaluation may be useful in patients with defects resulting from trauma, tumor, congenital abnormalities, or developmental disorders. Diagnosis, surgical management, and long-term follow-up evaluation may be aided by improved understanding of bony contour and volume analysis. Computer designed prostheses can be fabricated to precisely match bony defects and may be used as an alloplastic implant or as a model to aid intraoperative contouring of an autogenous bone graft. The limitations of three dimensional imaging include artifacts in the reconstructed images, increased radiation exposure, and increased cost. The technology is still evolving and the indications and benefits remain undefined at the present time. PMID- 1457064 TI - Impressions for oculofacial prosthetics. AB - Primary to the development of an acceptable and functional facial prosthesis is the impression procedure. The fabrication of a facial prosthesis combines the art and science of anatomy, cosmesis, and function, to develop a nonliving substitute to replace altered, missing, or defective regions of the head and neck area. Success depends on patient's cooperation, motivation, and commitment to treatment as well as the technical and artistic scope of the facial prosthetic service. PMID- 1457065 TI - Comment: calculation of the conjunctival area in an anophthalmic socket. PMID- 1457066 TI - Impression making, sculpting, and coloring of orbital prostheses. AB - The replacement of any anatomic structure by artificial means remains a challenge. This is particularly true in the facial area. The replacement must be one which blends with the adjacent tissues as well as replaces the missing structures. Careful planning and meticulous attention to detail in fabrication of a prosthesis can enable the maxillofacial prosthodontist to make a major contribution in the rehabilitation of the patient with an orbital defect. PMID- 1457067 TI - Prosthetic rehabilitation of the anophthalmic socket using osseointegrated fixtures. PMID- 1457068 TI - The ocularists' management of congenital microphthalmos and anophthalmos. AB - Early socket stimulation is crucial for management of congenital anophthalmos and microphthalmos among infants. Progressive sized hard conformers and lid expansion devices can expand the small socket in these patients. The ocularists' management of these two conditions is discussed and techniques are introduced. PMID- 1457069 TI - Hydrophilic expanders for the congenital anophthalmic socket. AB - The congenitally contracted socket often poses a challenging management problem; early surgery may be necessary in spite of the attendant difficulties. A series of patients is presented, with particular emphasis upon the use of a new hydrophilic expander in the severely contracted socket, to illustrate our current management protocol. Factors pertinent to orbital development and growth are discussed. Two types of contracted sockets are identified that appear to correlate with the presence or absence of an eye or ocular remnant. Use of a hydrophilic expander in the severely contracted anophthalmic socket with marked lid phimosis has enabled subsequent fitting and retention of a hard conformer in many of these cases, thus obviating early interventional surgery. PMID- 1457070 TI - An expansion prosthesis for the microphthalmic socket. AB - An expansion prosthesis has been developed for the anophthalmic or microphthalmic socket. Orthodontic wire covered with silicone tubing is fused onto a conventional methyl-methacrylate ocular prosthesis. The use of this device is illustrated in a case report. PMID- 1457071 TI - Orbito-palpebral reconstruction in anophthalmos and severe congenital microphthalmos. AB - In patients with congenital anophthalmos and severe microphthalmos, a tiny orbit and socket exist with little eyelids, frequently preventing retention of a standard conformer or prosthesis. Socket expansion is sometimes impossible with microorbitism; the retention of a prosthesis is also difficult when malformations of the eyelids exist. The treatment of these difficult cases includes three stages. The first stage is orbital expansion that depends on the cephalometric studies of the patient: transverse osteotomy on the maxilla and the zygomatic bone with lateral bar by extracranial route, vertical osteotomy on the roof of the orbit by intracranial route. In some cases, the osteotomy includes expansion in the transverse and vertical diameter with bone grafts in the defects and on the lateral and superior rims. Simultaneously, socket expansion is performed by incision of the conjunctival sac circumferentially, with mucosal or split skin grafts on a conformer. The second stage includes eyelid reconstruction by different flaps. A third stage is frequently needed for correction of eyelid malposition on the prosthesis: ptosis, entropion surgery. Two cases of congenital anophthalmos are reported. Methods and indications of treatment are discussed. PMID- 1457072 TI - Orbito-palpebral reconstruction in two cases of incomplete cryptophthalmos. AB - Two cases of congenital symblepharon (variant of cryptophthalmos) are reported. Cryptophthalmos is a very rare congenital defect, with incomplete or complete failure in the development of one or both eyelids with skin recovering the anterior segment. Surgical treatment is described including expansion of the conjunctival fornix with eyeball conservation if possible. At the same time or later, the upper eyelid is reconstructed by inferior eyelid flap. The ophthalmic features of cryptophthalmos and its systemic associations are reviewed. PMID- 1457073 TI - The myofibroblast and the anophthalmic socket. AB - One of the greatest advances in the understanding of wound healing was the identification and characterization of the myofibroblast by Gabbiani in 1971. Since that time this contractile cell has been found in the early stages of wound healing and in many pathologic states. In a recent study, the myofibroblast was found in healing and contracting anophthalmic sockets. PMID- 1457074 TI - Structure of 2,3-naphthalenedicarboxylic acid. AB - C12H8O4, M(r) = 216.20, monoclinic, C2/c, a = 5.087 (2), b = 19.222 (3), c = 9.552 (2) A, beta = 93.81 (3) degrees, V = 932.0 (5) A3, Z = 4, Dx = 1.54 g cm-3, lambda = 0.71073 A, mu = 1.09 cm-1, F(000) = 488, T = 295 K, R = 0.037 for 687 unique reflections having I > 3 sigma (I). In the structure reported here, a twofold axis lies in the plane of the molecule and bisects the three central ring bonds. The average C--C bond distance in the naphthalene core is 1.401 (27) A and the average interior angle 120.0 (14) degrees. The average deviation of the C atoms comprising the naphthalene rings from the best least-squares plane describing the rings is 0.021 (8) A. The plane of the single unique carboxylic acid group makes a dihedral angle of 33.1 (1) degrees with the least-squares plane of the naphthalene core. The carboxylic acid group, in which the observed O -H distance is 1.00 (3) A, forms a cyclic-dimer hydrogen bond across a center of inversion with the H...O(acceptor) distance 1.68 (3) A, the O...O-(acceptor) distance 2.676 (2) A and the O--H...O-(acceptor) angle 174 (3) degrees. The C--O bond lengths indicate no disorder in the carboxylic acid dimers. The molecules are arranged in stacks with the naphthalene cores parallel to the (102) plane and with the hydrogen bonds of the acid groups linking adjacent stacks. This structure of 2,3-naphthalenedicarboxylic acid is essentially the same as that of o-phthalic acid, but with the b cell edge correspondingly larger to accommodate the additional aromatic ring. PMID- 1457075 TI - Structure of 9-epiquinine hydrochloride dihydrate versus antimalarial activity. AB - 9-Epiquinine hydrochloride dihydrate [(9S)-6'-methoxycinchonan-9-ol hydrochloride dihydrate], C20H25N2O2+.Cl-.2H2O, M(r) = 396.9, orthorhombic, P212121, a = 8.059 (2), b = 11.537 (3), c = 22.311 (6) A, V = 2074.1 (9) A3, Z = 4, Dx = 1.271 g cm 3, Cu K alpha, lambda = 1.54178 A, mu = 18.58 cm-1, F(000) = 848, room temperature, final R = 6.56% for 1344 reflections with magnitude of Fo > 3 sigma (F). 9-Epiquinine crystallized as a hydrated tertiary amine hydrochloride salt. The intramolecular N(1)+ ...O distance is 2.816 A. All H atoms attached to O or N atoms form intermolecular hydrogen bonds. The Cl ion is involved in four hydrogen bonds including one with the hydroxyl group of 9-epiquinine. The N(1)+-H moiety hydrogen bonds to a water molecule. The O(12)-C(9)...N(1)+-H(1) torsion angle was equal to -0.2 (3.8) degrees in comparison to 97.0 degrees for quinidine sulfate [Karle & Karle (1981). Proc. Natl Acad. Sci. USA, 78, 5938-5941]. Two theories have been proposed in the literature to explain the low antimalarial activity of 9-epiquinine. The crystal structure of 9-epiquinine hydrochloride is not consistent with the hypothesis that 9-epiquinine prefers to form intramolecular rather than intermolecular hydrogen bonds, but is consistent with the hypothesis that N(1) and the hydroxyl group of 9-epiquinine are in an orientation which is unfavorable towards exerting antimalarial activity. PMID- 1457076 TI - Ethyl (2R,3R,SR)-3-(ethoxycarbonyloxy)-2-[1-(p-tolylsulfinyl) cyclopropyl]-1 pyrrolidinecarboxylate. AB - The title compound, derived in four steps beginning with the cyclopropanation reaction of the anion of the alpha-sulfinyl ketimine (4R,SS)-4-(tert butyldimethylsilyloxy)-3,4-dihydro-5-(p-tolysul finyl)methyl)-2H-pyrrole with 2 chloroethyl trifluoromethanesulfonate, contains a shorter than expected bond (C(7)--C(8) 1.48(l) A) and a larger than expected angle (S(1)--C(6)--C(2) 123.2(6) in the cyclopropane framework. PMID- 1457077 TI - Racial differences in maximal vasodilatory capacity of forearm resistance vessels in normotensive young adults. AB - This study was performed to determine whether alterations in vascular structure exist in a biracial population of young (age 22.3 +/- 0.6 yrs [mean + SE]) normotensive men. We examined maximal vasodilatory capacity in 21 blacks and 20 whites (average blood pressure = 122/75 and 118/72 mm Hg, respectively). Forearm blood flow was determined at rest and after 10 min of ischemic handgrip exercise using venous occlusion plethysmography. Forearm vascular resistance was computed from blood flow and mean arterial blood pressure determined by auscultation. Minimum forearm vascular resistance was 23% higher in blacks (2.60 +/- 0.60) than in whites (2.11 +/- 0.41) (P = .005), and was unrelated to parental history of hypertension. The regression equation for minimum forearm vascular resistance (Y) and casual blood pressure (X) for blacks was Y = -1.782 + 0.0487X (r = 0.522); for whites it was Y = -1.165 + 0.0367X (r = 0.418). When the data were covaried on resting mean arterial blood pressure, blacks still had a higher minimum forearm vascular resistance (P = .014). The results suggest a racial difference in the vascular structure of the forearm resistance vessels. PMID- 1457078 TI - The relation of culturally influenced lay models of hypertension to compliance with treatment. AB - Problems in compliance with treatment and illness management have frequently been traced to differences between patients' explanatory models of illness and the biomedical model. We investigated the relationship of cultural beliefs about hypertension to compliance with treatment. Using semistructured interviews, we elicited the explanatory models of hypertension held by 60 black hypertensive women being treated at Charity Hospital in New Orleans. The patient sample was followed for 2 months to obtain data on compliance with antihypertensive treatment and blood pressure control. As described, 53% of the patient sample recognized two basic folk illness models: "high blood" and "high-pertension." Patients' illness models were significantly related to compliance with treatment at the P = .01 and .001 levels. Compliance was related to blood pressure control at the P = .05 level. These results indicate that culturally influenced health beliefs are an important influence on compliance and, in turn, blood pressure control. Improved understanding of these problems by physicians may improve the management of their patients' illness. PMID- 1457079 TI - Relationship of the renin-angiotensin system and systemic arterial pressure to sodium excretion during atrial natriuretic peptide infusion in men. AB - The goal of this study was to evaluate the relative contribution of the renin angiotensin system and mean arterial pressure to sodium excretion and urine flow rate during an infusion of atrial natriuretic peptide (ANP) at physiologically relevant doses in humans. Eight normal volunteers were studied during five periods: (1) baseline in the supine position; (2) during an infusion of ANP at physiologic doses (0.01 micrograms/kg/min) in the supine position; (3) during ANP infusion and 60 degrees head-up tilt; (4) during ANP infusion, head-up tilt, and interruption of the renin-angiotensin axis with the angiotensin converting enzyme inhibitor (ACEI) enalaprilat; and (5) in the supine position during ANP infusion and ACEI. Infusion of ANP in the supine posture significantly increased urine flow rate and sodium excretion compared to baseline while mean arterial pressure and plasma renin activity were unchanged. During head-up tilt and ANP infusion, urine flow rate and sodium excretion were no longer significantly elevated over baseline while mean arterial pressure decreased and plasma angiotensin II levels increased. Addition of ACEI caused a marked diminution of urine flow rate and sodium excretion compared to baseline levels despite continued ANP infusion. Although mean arterial pressure after ACEI administration was lower than baseline, it was not significantly different from the non-ACEI head-up tilt state. Placing subjects in the supine position during ANP infusion and ACEI administration increased mean arterial pressure to levels that were no longer different from baseline, but urine flow rate and sodium excretion remained significantly depressed to the same degree as during head-up tilt with ACEI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457081 TI - Ganglion atrial natriuretic peptide in NaCl sensitive spontaneously hypertensive rats. AB - Reports from other laboratories have shown that atrial natriuretic peptide (ANP) stores in sympathetic ganglia are increased during dietary NaCl supplementation in normotensive rats. We have previously demonstrated that dietary NaCl supplementation in NaCl sensitive spontaneously hypertensive rats (SHR-S) exacerbates hypertension and enhances peripheral sympathetic nervous system activity, while NaCl resistant Wistar-Kyoto (WKY) rats show neither response. Since endogenous ANP may inhibit ganglion transmission, an inability of SHR-S to increase ganglion ANP appropriately in response to high NaCl feeding could contribute to the NaCl induced increase in sympathetic nervous system activity and blood pressure in this model, while an increase in ganglion ANP in NaCl supplemented WKY would tend to prevent sympathetic activity and blood pressure from rising. The current study tested the hypothesis that ganglion ANP levels increase in WKY but not in SHR-S during dietary NaCl supplementation. Male SHR-S and WKY rats were placed on 1% or 8% NaCl diets at 7 weeks of age. The rats were decapitated without prior anesthesia 3 weeks later, and the superior cervical and celiac ganglia were removed for the measurement of ANP by radioimmunoassay. Dietary NaCl supplementation produced significant increases in blood pressure in SHR-S, but not in WKY rats; the high NaCl diet was associated with significant increases in the ANP content of superior cervical and celiac ganglia in WKY rats, but not in SHR-S.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457080 TI - Angiotensin II regulates cytochrome P-450 steroid hydroxylase enzyme expression in human adrenal glomerulosa cells. AB - We have examined the regulation of cytochrome P-450 side chain cleavage enzyme (P 450SCC) and P-45011 beta (18) hydroxylase (P-450(11) beta) enzyme expression by angiotensin II (AII), the major regulator of aldosterone biosynthesis, in cultured human adrenal glomerulosa cells. We also examined the effect of lipoxygenase products of arachidonic acid on the expression of these enzymes since it has been previously shown that the 12-lipoxygenase pathway plays a key role in AII-induced aldosterone synthesis in rat and human adrenal glomerulosa cells. AII (10(-7) mol/L) induced a 3-fold stimulation of P-450SCC and over a 2 fold increase in P-450(11) beta protein expression. The 12-lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) caused a 2-fold increase in P-450(11) beta levels without altering P-450SCC levels. These results show for the first time that AII can directly increase the levels of P-450SCC and P-450(11) beta enzymes in glomerulosa cells. The results also suggest that 12-HETE may mediate long term effects of AII action by stimulating P-450(11) beta levels. PMID- 1457082 TI - Usefulness of atrial natriuretic peptide assay in primary aldosteronism. AB - Atrial natriuretic peptide (ANP) can be elevated in conditions which are characterized by increased atrial pressure and or expanded plasma volume. We and others have previously shown a significant increase of ANP plasma levels in a small number of patients with primary aldosteronism. In this study we have extended the assay of plasma ANP to a larger number of patients. We studied ANP plasma levels before and after upright posture and acute sodium load in 16 patients with aldosteronoma (APA) and 13 with idiopathic aldosteronism (IHA). The study was repeated also after the removal of aldosteronoma. In patients with primary aldosteronism, the mean supine ANP plasma level was significantly higher than in the age matched normal subject group; supine ANP was significantly higher in the APA than in the IHA group. The decrease of ANP levels after upright posture was significant in both groups. The ANP increase after acute saline load was similar in APA and in IHA. After the removal of aldosteronoma ANP values returned to normal. In conclusion, it is confirmed that plasma ANP levels are elevated in primary aldosteronism and could reflect a greater volume expansion in patients with APA. Despite this difference, ANP still responds to physiological stimuli in both groups. Finally, ANP measurement can provide an additional tool in the differential diagnosis between APA and IHA. PMID- 1457083 TI - Effects of endothelin-1 and vasopressin on resistance arteries of spontaneously hypertensive rats. AB - Previous studies have shown an impairment of responsiveness of resistance arteries to endothelin-1 in experimental hypertensive rats. This study was undertaken to demonstrate whether responses were also blunted in adult 20-week old spontaneously hypertensive rats (SHR). Resistance arteries from the mesenteric vascular bed exhibited normal active tension responses to endothelin-1 and arginine vasopressin, and exaggerated responses to norepinephrine. Since the media was thicker in SHR, media stress responses to endothelin-1 and arginine vasopressin were significantly impaired, while norepinephrine media stress responses were similar in SHR and Wistar-Kyoto rats (WKY). Active pressure responses to endothelin-1, arginine vasopressin, and norepinephrine were significantly amplified by the narrowed lumen of blood vessels in SHR. Additionally, media cross-sectional area was similar in SHR and WKY, but was greater in SHR when normalized for the smaller body weight of the hypertensive rats. These results demonstrate the presence of remodeling in resistance arteries of 20-week-old SHR, and show that the altered morphology of these blood vessels may significantly amplify impaired wall stress responses to endothelin-1 and arginine vasopressin, which may contribute to elevation of blood pressure. PMID- 1457084 TI - Lack of effect of parathyroid hormone on calcium homeostasis in rat platelets. AB - The in vitro effects of parathyroid hormone on Ca2+ handling by fura-2 loaded rat platelets were studied. The incubation of these platelets with rat parathyroid hormone (1-34) for 10 min had no effect on intracellular fura-2 metabolism or [Ca2+]i in the resting state. The [Ca2+]i response to 0.1 U/mL thrombin was unaffected by preincubation with parathyroid hormone in the presence or absence of extracellular Ca2+. Furthermore, the recovery rate of [Ca2+]i after the thrombin-induced peak in Ca(2+)-depleted media was not altered with parathyroid hormone. These data indicate that parathyroid hormone may not have a significant effect on Ca2+ homeostasis in rat platelets in unstimulated and stimulated conditions. PMID- 1457085 TI - Glucose, insulin, and lipid metabolism in doxazosin-treated patients with hypertension. AB - The metabolic changes associated with doxazosin treatment of hypertension were evaluated in ten patients with mild hypertension (mean +/- SEM = 150 +/- 3/100 +/ 1 mm Hg) and a plasma triglyceride (TG) concentration > 1.50 mmol/L. The blood pressure was lower after 4 to 6 months of doxazosin treatment (mean +/- SEM = 134 +/- 4/87 +/- 1 mm Hg), which was also associated with a significantly lower plasma insulin response to a 75 g oral glucose load, and lower plasma TG and cholesterol concentrations. In addition, insulin-mediated glucose uptake was significantly greater after doxazosin treatment. These data suggest that doxazosin treatment of patients with mild hypertension is associated with changes in insulin and lipid metabolism that should decrease the risk of coronary heart disease. PMID- 1457086 TI - In vivo measurement of atrial natriuretic peptide receptors using nuclear imaging. AB - We have successfully visualized atrial natriuretic peptide (ANP) receptors in vivo using nuclear imaging. 123I-Labelled ANP, injected in green vervet monkeys, was rapidly bound to ANP receptors in the kidneys and lungs. That the observed uptake was receptor mediated was demonstrated with competition studies using simultaneous injection of unlabelled ANP 99-126. It was possible to distinguish between the ANP receptor subtypes by the use of selective antagonists. Thus coinjection of ANP 102-121-des[Gln, Ser, Gly, Leu, Gly] (C-ANP), an ANP analog that selectively binds to the ANP C-receptor, decreased uptake in the kidneys by 50% but increased relative uptake in the lungs and soft tissues. This method permits for the first time, the dynamic in vivo analysis of ANP receptors and their interaction with endogenous ligand. Differences and changes in local ANP receptor concentrations and occupancy could be detected. Since ANP receptor density and affinity are influenced by various physiological and pathological conditions, clinical and diagnostic applications seem possible. PMID- 1457088 TI - Continuous noninvasive recording of arterial pressure. PMID- 1457087 TI - Effects of angiotensin converting enzyme inhibitors and calcium antagonists on atrial natriuretic peptide release and action and on albumin excretion rate in hypertensive insulin-dependent diabetic patients. AB - Abnormalities in sodium homeostasis and in atrial natriuretic peptide (ANP) behavior could play a role in determining and accelerating the development of glomerular hypertension, hypertension, and microalbuminuria in insulin-dependent diabetes. The aim of the present study was to investigate in 32 hypertensive insulin-dependent diabetic patients (HD) with an altered albumin excretion rate the natriuretic response and ANP release to saline load (2 mmol/kg 90 min, and the effects angiotensin converting enzyme inhibitor therapy 2.5 to 5.0 mg cilazapril, once daily), and calcium antagonists (sustained release verapamil: 120 to 240 mg Isoptin Press, once daily, and long acting nifedipine: 20 to 40 mg Adalat AR, twice daily) on sodium homeostasis and albumin excretion rate. Eight normal subjects matched for sex, age, and weight served as controls. The 32 HD patients showed a blunted response in ANP release and sodium excretion during saline infusion in comparison with controls. The cilazapril and verapamil treatments were tested in 16 of the 32 HD patients and were both effective in ameliorating natriuretic and ANP response to saline load and in decreasing albumin excretion rate. The combined cilazapril and verapamil treatment further improved both these parameters in these patients, although blood pressure levels were comparable. The other 16 HD patients underwent sequential verapamil and nifedipine treatment. Verapamil was more effective than nifedipine in improving natriuresis and ANP release to saline load and in lowering the albumin excretion rate. The results of the present study demonstrate that sodium homeostasis and ANP release are altered in hypertensive nephropathic patients, and both cilazapril and verapamil are more effective than nifedipine in ameliorating natriuresis, ANP release, and albumin excretion rate. PMID- 1457089 TI - Pitfalls in the measurement of blood pressure. PMID- 1457090 TI - Atrial natriuretic factor and hypertension: a response to Hollister and Inagami. PMID- 1457091 TI - Utilization of biosensors and chemical sensors for space applications. AB - There will be a need for a wide array of chemical sensors for biomedical experimentation and for the monitoring of water and air recycling processes on Space Station Freedom. The infrequent logistics flights of the Space Shuttle will necessitate onboard analysis. The advantages of biosensors and chemical sensors over conventional analysis onboard spacecraft are manifold. They require less crew time, space, and power. Sample treatment is not needed. Real time or near real time monitoring is possible, in some cases on a continuous basis. Sensor signals in digitized form can be transmitted to the ground. Types and requirements for chemical sensors to be used in biomedical experimentation and monitoring of water recycling during long-term space missions are discussed. PMID- 1457092 TI - Binding kinetics of antigen by immobilized antibody: influence of reaction order and external diffusional limitations. AB - The influence of reaction order and external mass transfer limitations on the binding kinetics of antigen in solution to antibody covalently or non-covalently attached to a cylindrical fiber-optic biosensor is presented. Both single-step and dual-step binding of antigen to antibody is considered. The rate of attachment of antigen to antibody is linear for all reaction orders in the time frame (100 min) considered. The rate of attainment of saturation levels of antigen in solution close to the surface is very rapid (within 20 min). An increase in the presence of mass transfer (denoted by a Damkohler number increase) decreases the saturation level of the antigen close to the surface, and the rate of antigen attachment to the antibody covalently or non-covalently bound on the surface for one-half, one, one and a half, and second-order reaction. As intuitively expected, an increase in the initial antigen concentration in solution increases the saturation level of the antigen close to the surface, and the rate of antigen attachment to the antibody covalently bound on the surface for all the reaction orders considered. Non-dimensional plots presented in the analysis help extend the analysis to different antigen-antibody systems. A decrease in the external diffusional limitations has an effect of decreasing the effect of reaction order on the saturation levels of antigen close to the surface and the rate of attachment of the antigen in solution to the antibody on the surface. PMID- 1457093 TI - Calibration in dogs of a subcutaneous miniaturized glucose sensor using a glucose meter for blood glucose determination. AB - The feasibility of calibrating a glucose sensor by using a wearable glucose meter for blood glucose determination and moderate variations of blood glucose concentration was assessed. Six miniaturized glucose sensors were implanted in the subcutaneous tissue of conscious dogs, and the parameters used for the in vivo calibration of the sensor (sensitivity coefficient and extrapolated current in the absence of glucose) were determined from values of blood glucose and sensor response obtained during glucose infusion. (1) Venous plasma glucose level and venous total blood glucose level were measured simultaneously on the same sample, using a Beckman analyser and a Glucometer II, respectively. The regression between plasma glucose (x) and whole blood glucose (y) was y = 1.12x 0.08 mM (n = 114 values, r = 0.96, p = 0.0001). The error grid analysis indicated that the use of a Glucometer II for blood glucose determination was appropriate in dogs. (2) The in vivo sensitivity coefficients were 0.57 +/- 0.11 nA mM-1 when determined from plasma glucose, and 0.51 +/- 0.07 nA mM-1 when determined from whole blood glucose (t = 1.53, p = 0.18, n.s.). The background currents were 0.88 +/- 0.57 nA when determined from plasma glucose, and 0.63 +/- 0.77 nA when determined from whole blood glucose (t = 0.82, p = 0.45, n.s.). (3) The regression equation of the estimation of the subcutaneous glucose level obtained from the two methods was y = 1.04x + 0.56 mM (n = 171 values, r = 0.98, p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457094 TI - Amperometric glucose biosensor with extended concentration range utilizing complexation effect of borate. AB - Borate buffer strongly decreases amperometric response of a glucose oxidase linked pO2 or H2O2 sensing electrode, extending substantially its linear calibration range. With increasing pH and concentration of the buffer the upper limit for glucose can be varied between 1 and 30 mmol l-1 glucose. The effect of borate ion is explained by the rapid complexation of glucose decreasing the equilibrium concentration of free beta-anomer, the specific substrate of glucose oxidase. The high loading of cross-linked enzyme inside the sensor membrane is necessary for the measurement to ensure an almost constant response factor (delta i per 1 mmol l-1) between pH 5 and 10. Analysis in stirred solution and in a flow through system has been employed for the measurement of elevated glucose levels in heparinized human blood or plasma samples. PMID- 1457095 TI - Structural and ultrastructural pattern of the embryonic and early foetal human liver. AB - With the aim of stressing the main steps which characterize the early development of the human foetal liver, fragments of hepatic buds of 7-12 weeks of pregnancy have been processed for light and scanning electron microscopy; Vial and Porter technique for isolated cells has been utilized too. The obtained results can be summarized as follows. At the 7th-8th weeks the hepatocytes show a globose shape, their surface is furnished with scattered and irregular evaginations and they are arranged in loose and narrow ribbons, separated by vascular spaces; the hepatocytes are tightly connected with haemopoietic cells, usually furnished with hyperchromatic nuclei. On the other hand, the hepatic parenchyma shows a compact pattern at the 11th-12th weeks. The hepatocytes have acquired a polyhydric shape and their faces are usually interlocked with the plasmatic membrane of the adjoining elements than in three fields: (a) the face projecting to the vascular walls with which they are going to form the Disse spaces; (b) the opposite side in which the membranes of neighbouring cells often appear spaced to line the primitive biliary canaliculi; and (c) the areas in which hemispheric and deep hollows of the hepatocyte surface hold haemopoietic elements. The obtained results demonstrate that the developing hepatic buds undergo deep structural changes, at level of the parenchyma and vascular system, in the studied period. PMID- 1457096 TI - Borderline hypertension: relationship between job and psychophysiological profile. AB - To identify relationships among hypertension, job and cardiovascular reactivity we studied 81 borderline hypertensives divided into labourers (L), white collars (W) and managers (M). After behavioral analysis, they underwent 4 tests: arithmetic, Sacks, acoustic, electric. Along the entire sitting, muscular contraction, skin conductance (SCL), peripheric temperature (THP), SBP, DBP and HR were taken, every 30". Depression, obsessive-compulsive, anxiety and neurotic traits were found in W. SBP, DBP and HR were not significantly different. Failed recovery curves of SCL were identified in M and W, but the presence of abnormal response profile, of both, SCL and THP, only in W. This autonomic dysreactivity, previously recognized as a possible characteristic of the prehypertensive condition, could uncover the role of certain work stressful condition to increase the sympathetic drive underlying hypertension. PMID- 1457097 TI - Cells from human bone giant cell tumors show a [Ca2+]o-sensing. AB - Giant cells from a human giant cell tumor of bone, showing several osteoclast features were tested for their capability of detecting the [Ca2+]o by a receptor like [Ca2+]o sensing. We found that cultured cells responded to elevation of [Ca2+]o, obtained adding 4 mM Ca2+ to the 2 mM Ca2+ containing buffer, by a transient increase of [Ca2+]i. Proliferative cells induced to differentiate by treatment with 10(-8) M 1,25 dihydroxyvitamin D3, were upregulated in their capability of responding to elevated [Ca2+]o. In fact, in this circumstance, the peak of [Ca2+]o-induced [Ca2+]i rise was increased compared to untreated cells. This suggests that 1,25 dihydroxyvitamin D3 induces a more efficient regulation of osteoclast activity. PMID- 1457098 TI - [Use of a protein-free medium for the in vitro development of sheep embryos]. AB - The employment of protein-free medium for the culture of ovine embryos collected at the 1-2 cell stage from superovulated ewes was investigated. For this purpose sheep zygotes were randomly allocated in four treatment groups: T1) CZB medium + bovine serum albumin (BSA) on sheep oviductal monolayer (SOM), T2) CZB + polyvinyl alcohol (PVA) + SOM, T3) CZB + PVA + SOM supplemented with inositol (I) and serine (S), T4) TCM 199 + 10% fetal calf serum + SOM. Standard culture conditions were 2 ml of medium in 35 mm Petri dishes, under 5% CO2 in air at 39 degrees C. The percentages of morulae and blastocysts were recorded after 4 and 7 days of culture. After 4 days of culture there was no significant difference (P > 0.05) in the percentage of morulae between embryos cultured in T1 (86%), T2 (85%), T3 (88.8%), and T4 (87.5%). After 7 days the percentages of blastocysts were T1 (70%), T2 (50%), T3 (55.5%) and T4 (46.8%). These data suggest that a protein-free medium, CZB + PVA and CZB + PVA + I + S, can support ovine preimplantation embryo development in vitro; however CZB medium supplemented with BSA enhances development to blastocyst. PMID- 1457099 TI - [Microencapsulation in Na-alginate and in vitro development of sheep blastomeres]. AB - Embryos at 4 cell stage obtained from Sarda ewes superovulated with FSHp (Sigma) were micromanipulated in order to obtain single blastomeres (1/4 E). The 1/4 E have been located randomly in two groups. In the first (Group A n. 30) the 1/4 E have been put back in empty zonae pellucidae; in the second (Group B n. 21) they have been microencapsulated in sodium alginate (1.1%) by dropping cell-alginate solution in a 1.5% CaCl2. Each capsule (1 mm diameter) contained four 1/4 E. The blastomeres have been co-cultured for 5 days in CZB medium on oviductal cell monolayer in a humidified incubator (5% CO2, 95% air, 38.5 degrees C). No differences were found between the groups reaching blastocyst stage after the end of the culture period (A 50%-B 47%). PMID- 1457100 TI - [Muscle reinnervation in rats treated with vitamin E]. AB - During muscle reinnervation, a transitory phase of polyinnervation occurs. In reinnervated muscles of vitamin E deficient rats, sprouting and polyinnervation are increased with respect to reinnervated controls. In this work, polyinnervation was observed in reinnervated extensor digitorum longus (edl) muscle of rats treated with pharmacological doses of vitamin E. Sciatic nerve was crushed and edl muscle was examined electrophysiologically at 30, 40 and 60 days after denervation. The percentage of polyinnervated cells in controls peaked at 30 days and thus it decreased. In muscles of vitamin E treated rats, the time course of percentage of polyinnervated muscle cells was qualitatively the same, but it was decreased at all times. PMID- 1457101 TI - [Different behavior of phagocytes in young and old subjects]. AB - Ageing is a dynamic phenomenon in which there is a physiological decay in all the functions of the individual. The consequence is an increased susceptibility to infections, autoimmune diseases and cancer. Phagocytic cells as polymorphonuclear leukocytes (PMNL) and monocytes (Mo) are of prime importance in the defence against invasive agents, PMNL and Mo seek out and destroy invading micro organisms. Chemotaxis and phagocytosis are two mechanisms that are activated by these cells for this purpose. In this study, using "in vitro" techniques, we have verified if, at the level of such functions of cell defense, there could be variations in elderly subjects with respect to younger subjects. Our results show a chemotactic activity of PMNL in the elderly that is higher and a phagocytic activity that is lower. As regards Mo, there is a lower chemotactic activity in the elderly and only a slight difference in phagocytic activity with respect to the younger subjects. These results are in agreement with those found at the clinical level showing the elderly less protected from infection with respect to younger subjects. PMID- 1457102 TI - [Modifications of the Portoscuso ecosystem. Distribution, accumulation,and dynamics of pollutants. I. Observations on animal tissues]. AB - In order to assess the extent of environmental pollution by Pb, Cd and Zn in the industrial area of Portoscuso (Southwestern Sardinia-Italy), anatomohistopathological, histochemical and chemical tests were carried out on the heart, liver, kidneys and bones of sheep slaughtered in the local abattoir. On microscopic examination, degenerative lesions were severe in liver and kidneys and slight in the heart; histochemical stainings clearly showed a notable presence of Zn, while spectrophotometric examination confirmed, besides Zn pollution, very high tissue concentrations of Pb and Cd. The Authors conclude that other trial observations over larger areas are necessary. PMID- 1457103 TI - Effect of one booster dose in antirabies vaccination. AB - The antibody response obtained after one booster dose of rabies vaccine prepared in suckling mice brains at Servico de Saude Publica da Cidade do Rio de Janeiro is described. Four prime vaccinal groups were used: group I, persons who had received 16 doses 10 years before this investigation; group II, persons who had received 5 doses of the vaccine 10 years before; group III, persons who had received 9 doses 5 years before; and group IV, persons who had received 16 doses 5 years before. One booster dose of the vaccine was administered to all persons involved in the study. Blood samples were collected before vaccination (day 0), then 7 and 30 days after vaccination. Antibody titres were determined by seroneutralization test in mice (SWM). The results demonstrated that all persons who had been treated with 5, 9 or 16 doses of the vaccine 5 to 10 years before had their antibody titres increased on the 7th and 30th days after one booster dose. PMID- 1457104 TI - Purification process monitoring in monoclonal antibody preparation: contamination with viruses, DNA and peptide growth factors. AB - Administration in vivo of monoclonal antibodies to humans is challenged by considerations regarding their safety. Contamination with viruses, potentially oncogenic nucleic acids and biologically active components like growth factors and hormones forms a serious point of concern in this respect. We have investigated the potential risk of viral contamination by measuring the reduction of 12 different viruses (after spiking) in the standard downstream purification process of ascitic fluid. Depending on the type of virus added and the purification step employed, the reduction of infectious virus particles varies considerably. The overall reduction ranges from about 10(3), observed for a member of the family of Papovaviridae, to more than 10(12) for members of the families of Herpesviridae and Orthomyxoviridae. Using hybridization analysis with a mouse (genomic) DNA probe, we show that the amount of residual DNA in ascitic fluids may also vary considerably, ranging from 75 ng/ml to 1 microgram/ml. In crude preparations produced in cell culture, much lower DNA concentrations are found (0.3 ng/ml). When standard downstream purification procedures are applied to ascitic fluid, a significant reduction of residual DNA levels is observed in the purified monoclonal antibody preparations and in intermediate fractions. The overall reduction factors vary from about 10(3) to 10(4), which is also confirmed by spiking experiments with either purified DNA or crude chromatin-like DNA. Using in-vitro cellular assays, we further show that peptide growth factors like PDGF and TGF beta are present in considerable amounts in ascitic fluids. The observed biological activities, however, are completely eliminated during the purification steps applied. PMID- 1457105 TI - The use of bovine fibrin-streptokinase films for the determination of recombinant human plasminogen. AB - Plasminogen is a key component of the haemostatic system in man and the plasma derived protein molecule has been actively investigated. Within the last few years cDNA and the gene encoding plasminogen have been cloned and the protein has been expressed in a number of eukaryotic or prokaryotic systems. Yields of expressed plasminogen are frequently low. Currently available assays for plasminogen generally rely on the determination of antigen or utilize tripeptide substrates for measuring functional activity, and they have certain limitations. Assays employing relevant protein substrates offer an alternative way to measure function and overcome the drawbacks associated with the other tests. The use of fibrin films for the assay of low levels of recombinant plasminogen has not been described fully before. The two fibrin film-based assays described in this paper are significant additions to the array of assays available for plasminogen molecules. PMID- 1457106 TI - High growth reassortant influenza vaccine viruses: new approaches to their control. AB - When a new strain of an influenza virus is required to be incorporated into influenza vaccine, attempts are made to recombine such strains with laboratory adapted viruses, which will grow to high titre in order to improve the yield of the vaccine strain. It is important that such high growth reassortant vaccine strains are not contaminated with genes coding for the antigenic determinants of the high growth laboratory strain. We describe the characterization of two recent high growth reassortants and the application of the polymerase chain reaction to ensure their genetic identity and purity. PMID- 1457107 TI - Analysis of therapeutic growth hormone preparations: report of an interlaboratory collaborative study on growth hormone assay methodologies. AB - Recombinant DNA-derived human growth hormone (somatotropin) is widely used to treat growth hormone-deficient children. The potency of this product is determined by in-vivo bioassay in hypophysectomized rats, which is imprecise, costly and invasive, and there have been suggestions that it could safely be replaced with in-vitro or physico-chemical alternatives. In this report we present the results of a collaborative study designed to test this proposal. Somatotropin was modified by mild or severe proteolysis, mild or severe oxidation or treatment at high pH, and compared in a multi-centre collaborative study with unmodified somatotropin or with dimerized somatotropin. Participating laboratories included manufacturers and national control laboratories, and pharmacopoeial bioassays were compared with in-house in-vitro and physico chemical bioassays. Although performing adequately with untreated somatotropin, for degraded samples the in-vivo bioassays were relatively unresponsive to changes in the growth hormone molecule. In contrast, the physico-chemical assays, in particular the reverse-phase HPLC, performed with a high degree of selectivity. We conclude that in the case of somatotropin, the in-vivo bioassay can be removed from the routine product specification with an acceptable degree of security. This however does not obviate the requirement rigorously to demonstrate biological activity in-vivo during product development, nor may the conclusions of this study be applied to other therapeutic recombinant proteins without similar collaborative investigations. PMID- 1457108 TI - A collaborative study to assess the proficiency of laboratory estimates of potency of live measles vaccines. AB - A collaborative study was undertaken to assess the variability in estimates of the potency of measles vaccines. Overall a median variation of 2.0 log10 between estimates was observed. This was reduced to a median of 1.0 log10 when the potencies were expressed relative to a reference vaccine. A difference in the sensitivity between plaque assays and TCID50 assays was also reduced when relative potencies were used. The benefit of including a common reference preparation in vaccine assays was therefore demonstrated. For the vaccines assayed in this study, it was not necessary to use a measles reference of the same strain as the vaccines tested. We therefore recommend that measles vaccines be assayed against a single international reference preparation. PMID- 1457109 TI - Verifying the (we hope) verified: reference checking in the Journal of Clinical Anesthesia. PMID- 1457110 TI - Effect of low fresh gas flow rates on inspired gas composition in a circle absorber system. AB - STUDY OBJECTIVE: To determine the effects of fresh gas flow on inspired gas composition during low-flow anesthesia. DESIGN: Randomized trial with 2-hour observation periods in patients assigned to one of three groups. SETTING: Inpatient surgery clinic at a medical center. PATIENTS: Thirty-six patients undergoing abdominal surgery with low-flow anesthesia. INTERVENTIONS: Fresh gas flow was given at a starting rate of 5 L/min for 6 minutes. Thereafter, the fresh gas flow setting was nitrous oxide (N2O) 1 L/min and oxygen (O2) 0.6 L/min (Group 1), N2O 0.5 L/min and O2 0.5 L/min (Group 2), and with a moderate surplus of N2O and O2 with respect to the patient's O2 consumption (Group 3). MEASUREMENTS AND MAIN RESULTS: The inspired O2 concentration (FIO2) was measured using a paramagnetic technique, and N2O levels were measured with infrared sensors; the inspired nitrogen concentration (FIN2) was calculated by the following formula: FIN2 = 1-FIO2-FIN2O, where FIN2O is the inspired N2O concentration. After 1 hour of anesthesia, FIO2 was significantly lower in Group 1 than in Groups 2 and 3 (p < 0.01), and FIN2 was significantly higher in Groups 2 and 3 than in Group 1 (p < 0.01). After 2 hours of anesthesia, FIN2 returned to normal in Group 2 but continued to increase in Group 3. FIN2O was close to 0.7% only in Group 1. CONCLUSIONS: The same initial period of denitrogenation is not adequate to denitrogenate the circle system in all cases. The lower the fresh gas flow, the longer the initial period of denitrogenation should be. Various levels of fresh gas flow for low-flow anesthesia have been suggested, but none guarantees adequate control of inspired gas composition unless flowmeters are continuously adjusted. PMID- 1457111 TI - Desflurane potentiates atracurium in humans: a comparative study with isoflurane. AB - STUDY OBJECTIVE: (1) To evaluate the neuromuscular effects of desflurane and its interactions with atracurium and (2) to compare desflurane and isoflurane in these effects. DESIGN: Sequential entry of informed and consenting patients randomly assigned to receive desflurane (n = 25) or isoflurane (n = 25). SETTING: Operating suite of a county-university medical center. PATIENTS: Fifty adults, ASA physical status I, undergoing elective orthopedic surgery. INTERVENTIONS: Following establishment of steady desflurane or isoflurane anesthesia, at 1.25 minimum alveolar concentration (MAC) exhaled for 15 minutes, a randomly predetermined dose of atracurium (0.05, 0.1, or 0.15 mg/kg) was injected intravenously (IV). At the end of surgery, neostigmine 0.04 mg/kg IV was given to reverse the residual block. The neuromuscular effects of desflurane or isoflurane alone, and the dose-response relationship, time course, and reversibility of the neuromuscular effects of atracurium with either anesthetic, were examined in detail and compared using electromyographic quantification of the response of the first dorsal interosseous muscle to train-of-four (TOF) stimulation of the ulnar nerve. MEASUREMENTS AND MAIN RESULTS: TOF fade and depression of the first response (T1) of the TOF were measured in response to desflurane or isoflurane, atracurium, and neostigmine. Desflurane caused more TOF fade than isoflurane prior to atracurium administration. The TOF ratios were 0.91 +/- 0.02 and 0.98 +/ 0.01, respectively (p < 0.05). For other measured neuromuscular parameters, atracurium-induced depression tended to be greater in the presence of desflurane than in the presence of isoflurane, but none of the measured differences reached the statistical significance level of p < 0.05. The ED50, ED95, and 25-75% recovery index of atracurium were 0.038 mg/kg (95% confidence level; range 0.030 to 0.047 mg/kg), 0.11 mg/kg (0.095 to 0.14 mg/kg), and 31 +/- 4 minutes (means +/ SEM) with desflurane anesthesia, versus 0.043 mg/kg (0.035 to 0.052 mg/kg), 0.13 mg/kg (0.11 to 0.16 mg/kg), and 23 +/- 4 minutes with isoflurane anesthesia (p = 0.1-0.2). Continuation of either anesthetic at 1.25 MAC prevented complete recovery of neuromuscular functions spontaneously or following neostigmine 0.04 mg/kg. CONCLUSION: In ASA physical status I adults, 9% desflurane has neuromuscular effects equal to or slightly in excess of those of 1.6% isoflurane. PMID- 1457112 TI - Inguinal herniorrhaphy in young infants: perianesthetic complications and associated preanesthetic risk factors. AB - STUDY OBJECTIVES: (1) To prospectively observe and tabulate all perianesthetic complications in young infants undergoing herniorrhaphy with general anesthesia and (2) to identify all major postnatal complications and determine which, if any, might be significant risk factors for perianesthetic complications. DESIGN: Prospective case control study. SETTING: Columbus, Ohio, Children's Hospital, a teaching and tertiary referral center. PATIENTS: One hundred two consecutive infants 60 weeks postconceptual age (PCA) or younger undergoing herniorrhaphy with general anesthesia. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: All perianesthetic complications occurring during anesthesia, in the postanesthesia care unit (PACU), during the remaining hospital stay, and within 30 days of anesthesia were recorded, and a detailed postnatal history was compiled. Fifty five percent of 60 preterm infants [37 weeks gestational age (GA) or younger] and 50% of 42 term infants (older than 37 weeks GA) experienced at least one perianesthetic complication. Following discharge from the PACU, in-house complications were confined to the preterm group. Significant risk factors included a history of apnea, bradycardia, and ventilatory support for at least 24 hours after birth, mainly for respiratory distress syndrome. CONCLUSIONS: In a teaching hospital, prospectively observed perianesthetic complications can occur in more than 50% of infants 60 weeks PCA or younger undergoing herniorrhaphy with inhalation anesthesia. Infants younger than 49 weeks PCA with a significant preanesthetic risk factor should be monitored overnight for apnea and bradycardia. PMID- 1457113 TI - The effect of respiratory alkalosis on oxygen consumption in anesthetized patients. AB - STUDY OBJECTIVE: To investigate whether hyperventilation significantly altered oxygen consumption in anesthetized and paralyzed patients undergoing surgery. DESIGN: Open crossover trial with 1 hour of hyperventilation preceded and followed by 1 hour of normoventilation. SETTING: University medical center. PATIENTS: Eight patients (five men and three women) undergoing lengthy orthopedic surgery with general anesthesia and muscle paralysis. INTERVENTIONS: After baseline normoventilation for 1 hour (Period 1), the anesthetized patients were hyperventilated to an arterial carbon dioxide tension (PaCO2) of 20 to 25 mmHg for 1 hour (Period 2). Patients then experienced another hour of normoventilation (Period 3). MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables, electrocardiography, temperature, end-tidal partial pressure of CO2 (PETCO2), oxygen consumption (VO2), carbon dioxide production, and minute ventilation were continuously followed throughout the study, and arterial blood gases were drawn at the beginning and end of each study period. During the period of hyperventilation, pH was significantly higher and P.ETCO2 and PaCO2 significantly lower compared with the periods of normoventilation. VO2 was significantly increased during hyperventilation compared with the periods of normoventilation. Hemodynamic variables and temperature were similar in the three study periods. CONCLUSIONS: In anesthetized paralyzed patients, there is an increase in whole body VO2 with hypocapnic alkalosis. PMID- 1457114 TI - Performance evaluation of a draw-over vaporizer with a nonbreathing circuit during simulated adverse conditions. AB - STUDY OBJECTIVE: Performance evaluation of a draw-over vaporizer with a nonrebreathing circuit during simulated adverse conditions. DESIGN: Open laboratory study. SETTING: University hospital laboratory. MATERIALS AND INTERVENTIONS: The output (%) of a temperature-compensated Ohmeda Cyprane PAC (portable anesthesia complete) draw-over vaporizer (Ohmeda, Madison, WI) using isoflurane attached to a nonrebreathing circuit was tested in the laboratory during manual ventilation under normal and simulated adverse conditions. The adverse conditions tested were high ambient temperature and static and dynamic positional variation. MEASUREMENTS AND MAIN RESULTS: The results show that the output bias of the PAC vaporizer has a generally consistent profile as tested, except when placed in the 180 degrees full-inversion or 90 degrees anterior-tilt position. We also conducted trials with the Penlon ventilator (Ohmeda, Abingdon, Oxford, U.K.) attached to the circuit at each of its input ports. Ventilation at one input port produced dangerously high airway pressures (within the circuit), thus supporting the manufacturer's recommendation against the use of this port for positive-pressure ventilation. Using the recommended port, the test lung was seen to inflate and deflate appropriately, but, surprisingly, no vapor output was detected by the agent monitor at any vaporizer setting when using the ventilator at the recommended port. CONCLUSION: Anesthetists should be aware of the pitfalls and possible problems that may be associated with this type of anesthetic delivery system. PMID- 1457115 TI - Pharmacodynamic effects of three doses of ORG 9426 used for endotracheal intubation in humans. AB - STUDY OBJECTIVE: To determine the pharmacodynamic characteristics of three incremental doses of ORG 9426 used for endotracheal intubation in patients. DESIGN: Double-blind, randomized administration of one of three doses of intravenous ORG 9426. SETTING: Inpatients requiring surgery at Georgetown University Medical Center. PATIENTS: Thirty-six patients, ages 18 to 65, ASA physical status I, II, and III, scheduled for general surgery. INTERVENTIONS: After Georgetown University Institutional Review Board approval and patient consent, patients were premedicated with midazolam or droperidol. Anesthesia was induced with thiopental sodium and fentanyl. Anesthesia was maintained with 60% nitrous oxide in oxygen. The ulnar nerve was stimulated supramaximally with a 2 Hz train-of-four (TOF) every 20 seconds. Thumb contractions were measured with a force transducer. When TOF and anesthesia were stable, 2, 2.5, or 3 times the ED95 of ORG 9426 (570 micrograms/kg, 710 micrograms/kg, or 850 micrograms/kg) was administered randomly. Tracheal intubation was attempted at maximal depression of the first TOF response (T1). MEASUREMENTS AND MAIN RESULTS: The following parameters were measured: time interval from the injection of ORG 9426 to 90% depression of T1 (T1 90% block), maximal T1 depression (onset time), intubating conditions, clinical duration (time for return of T1 to 25% of control), heart rate (HR), blood pressure (BP), and any adverse clinical experience. ORG 9426 provided adequate intubating conditions in all patients but two, independent of the dose used. Its onset time was rapid, but increasing the dose did not shorten the onset. T1 90% block was achieved rapidly (75 +/- 25 seconds to 78 +/- 18 seconds, means +/- SD). The clinical duration of ORG 9426 was relatively short and lengthened with increasing doses (from 36 +/- 18 minutes at 570 micrograms/kg to 42 +/- 10 minutes at 850 micrograms/kg. Spontaneous twitch recovery from 10% to 25% was similar in all dosage groups (5 +/- 1 minutes to 6 +/- 4 minutes). No clinically significant changes in HR and BP and no adverse clinical experiences were noted in any group. CONCLUSION: These findings warrant further clinical evaluation of ORG 9426 for induction and maintenance of muscle relaxation in humans. PMID- 1457116 TI - Patient-controlled drug administration during local anesthesia: a comparison of midazolam, propofol, and alfentanil. AB - STUDY OBJECTIVE: To evaluate the perioperative effects of alfentanil, midazolam, and propofol when administered using a patient-controlled analgesia (PCA) device during local anesthesia. DESIGN: Randomized, single-blind comparative study. SETTING: Outpatient surgery center at a university teaching hospital. PATIENTS: Ninety outpatients undergoing minor elective surgical procedures with local anesthetic infiltration were assigned to one of three treatment groups. INTERVENTIONS: After premedication with midazolam 1 mg intravenously (IV) and fentanyl 50 micrograms IV, patients were allowed to self-administer 2 ml bolus doses of either alfentanil 250 micrograms/ml, midazolam 0.4 mg/ml, or propofol 10 mg/ml at minimal intervals of 3 minutes to supplement a basal infusion rate of 5 ml/hr. MEASUREMENTS AND MAIN RESULTS: The total intraoperative dosages of alfentanil, midazolam, and propofol were 2.7 +/- 1.1 mg, 4.7 +/- 2.7 mg, and 114 +/- 42 mg, respectively, for procedures lasting 48 +/- 28 minutes to 51 +/- 19 minutes (means +/- SD). Propofol produced more pain on injection (39% vs. 4% and 6% in the alfentanil and midazolam groups, respectively). Episodes of arterial oxygen saturation less than 90% were more frequent with alfentanil (28%) than with midazolam (3%) or propofol (13%). Using the visual analog scale, patients reported comparable levels of discomfort, anxiety, and sedation during the operation in all three treatment groups. Postoperative picture recall was significantly decreased with midazolam versus alfentanil and propofol. Finally, postoperative nausea was reported more frequently in the alfentanil group (29%) than in the midazolam (10%) or propofol (18%) groups, contributing to a significant prolongation of the discharge time in the alfentanil-treated patients. CONCLUSIONS: When self-administered as adjuvants during local anesthesia using a PCA delivery system, alfentanil, midazolam, and propofol were equally acceptable to patients. However, propofol and midazolam were associated with fewer perioperative complications than was alfentanil. PMID- 1457117 TI - Ketorolac or fentanyl to supplement local anesthesia? AB - STUDY OBJECTIVE: To evaluate the usefulness of ketorolac in the treatment of intraoperative pain refractory to the administration of local anesthetic alone. DESIGN: Intraoperative acute-pain treatment model consisting of awake, nonsedated patients who randomly received either an opioid or a study drug in a double-blind fashion. SETTING: University medical center. PATIENTS: Eighty patients who underwent breast biopsy, lumpectomy, or central venous catheter placement. INTERVENTIONS: Patients received either ketorolac 1 mg/kg intravenously (IV) up to a total dose of 60 mg or fentanyl 3 micrograms/kg IV up to a total dose of 250 micrograms to supplement the local anesthetic. MEASUREMENTS AND MAIN RESULTS: Verbal pain evaluation and the visual analog scale (VAS) were used for perioperative measurement of pain. Heart rate (HR), blood pressure, and respiratory rate (RR) were recorded before and after analgesic drug injections at 10-minute intervals, both intraoperatively and while the patient was in the postanesthesia care unit (PACU). Speed of recovery was quantified by p-deletion and digit substitution tests on admission to the PACU and at 30-minute intervals until discharge. The frequency of nausea, vomiting, and pruritus were recorded. There were no differences between the groups in perioperative verbal pain evaluation, VAS scores, HR, systolic blood pressure, diastolic blood pressure, or RR. Patients who received ketorolac exhibited a significantly lower frequency of intraoperative and postoperative medication administration intraoperatively, than those who received fentanyl. No additional pain medication was required by patients in the PACU in either group. CONCLUSIONS: Ketorolac is a useful alternative to fentanyl for the treatment of intraoperative pain refractory to the administration of local anesthetic alone during monitored anesthesia care. A decided advantage of ketorolac over fentanyl is the absence of nausea and vomiting in the intraoperative and postoperative periods. PMID- 1457118 TI - Anesthetic considerations of an infant with Beckwith-Wiedemann syndrome. AB - The case of a 3-day-old infant with Beckwith-Wiedemann syndrome who required anesthetic care during closure of an abdominal wall defect is presented. Beckwith Wiedemann syndrome comprises a constellation of clinical features, including macroglossia, macrosomia, omphalocele, visceromegaly, mild microcephaly, facial nevus flammeus, horizontal earlobe creases, and renal medullary dysplasia. Due to the high rate of omphalocele in this syndrome, anesthetic care is frequently required during the neonatal period. Many of these infants (greater than 50%) are born prematurely. Therefore, their anesthetic care may be further complicated by associated diseases of prematurity, such as hyaline membrane disease. Additional anesthetic implications of this syndrome relate to the occurrence and management of hypoglycemia and polycythemia. Careful intraoperative management of glucose homeostasis is particularly important, since eventual neurologic outcome and intelligence will be normal provided prolonged neonatal hypoglycemia is avoided. Preoperative evaluation of the cardiac and genitourinary system, including echocardiography and renal ultrasound, are recommended because of the frequent occurrence of associated anomalies with omphalocele. PMID- 1457119 TI - Intravenous nitroglycerin for uterine inversion. AB - Uterine inversion following vaginal delivery or during Cesarean section is rare. Cardiovascular instability resulting from blood loss is possible. This article describes the use of intravenous nitroglycerin as an alternative to the induction of general anesthesia and administration of volatile anesthetics to provide uterine relaxation. PMID- 1457120 TI - To define a specialty: a brief history of the American Board of Anesthesiology's first written examination. AB - The initial written examination of the American Board of Anesthesiology, a division of the American Board of Surgery, was given on March 28, 1939. For all anesthesiologists, this date has double significance. First, what was meant by anesthesiology as a medical specialty was defined through the questions posed on the first examination. Second, the physicians being tested that day were among the first physician-anesthetists to exploit the newly created path to recognition as specialists in the science and art of anesthesia by the American medical hierarchy. Gaining the support of organized medicine was an involved and arduous struggle that consumed most of the 1930s. A triumvirate of visionaries, Paul Wood, John Lundy, and Ralph Waters, was necessary to crystalize the goal of specialty recognition of physician-anesthetists. The first written examination was the consummation of this dream of equal status for anesthesia. The examination would not become repetitious, and within the first decade of testing, the style would change from an essay format to multiple-choice questions similar to the current form. PMID- 1457121 TI - Intraoral vascular malformation and airway management: a case report and review of the literature. AB - A patient with a large airway venous malformation underwent anesthesia for a tooth extraction. The procedure was uneventful until extubation, immediately after which complete airway obstruction resulted. After unsuccessful attempts to relieve the problem, the patient's trachea was reintubated. Laryngoscopy showed that the venous malformation in the airway had enlarged and was responsible for the airway obstruction. Another attempt at extubation after corrective maneuvers was again unsuccessful. A tracheostomy was required, which was eventually removed after a complete recovery. Anesthesiologists must be concerned with any airway vascular abnormality. Most abnormalities involving the airway are either hemangiomas or venous malformations. The anesthesiologist must diagnose the problem correctly because even minor manipulation of a venous malformation may result in exsanguination, or the malformation may become engorged and compromise the airway. PMID- 1457122 TI - Application of a laryngeal mask to a fiberoptic bronchoscope-aided tracheal intubation. PMID- 1457123 TI - Understanding and management of amniotic fluid embolism. PMID- 1457124 TI - Leukemia inhibitory factor--a puzzling polyfunctional regulator. AB - LIF seems likely to have important functions in the early developing embryo and in adult life can influence platelet formation, osteoblast and neuronal function, calcium and lipid metabolism and the production of acute-phase proteins. LIF appears usually to be produced and to function locally in various tissues, an arrangement that would minimize unwanted actions of this polyfunctional regulator. Nevertheless it remains puzzling what purpose is achieved by use of a regulator with potent actions on such a wide range of apparently unrelated tissues. PMID- 1457125 TI - Molecular genetics of leukemia inhibitory factor (LIF) and its receptor. PMID- 1457126 TI - Regulation of amphiregulin mRNA by TGF-beta in the human lung adenocarcinoma cell line A549. AB - Transforming growth factor beta is a strong growth inhibitor for many types of normal and transformed cells, although little is known on the mechanism of this anti-proliferative effect. The human lung adenocarcinoma cell line A549 is growth arrested by TGF-beta 1 and serves as a model for studying this effect. We describe that, concurrent with the inhibition of A549 cell growth, TGF-beta 1 treatment causes a dramatic reduction in the level of expression of the amphiregulin (AR) gene, a recently identified member of the EGF/TGF alpha family. Similar results were also observed with TGF-beta 2. Peak inhibition occurred at 24 hr of treatment and was reversible upon removal of TGF-beta 1. The level of AR protein secreted by A549 cells was also decreased by TGF-beta 1. In contrast, TGF alpha mRNA was not detected in these cells regardless of TGF-beta 1 treatment. Another TGF-beta inhibited cell line, PC-3 (human prostatic adenocarcinoma) also exhibited a decrease in AR message levels following exposure to TGF-beta 1. The growth inhibitory effects of TGF-beta may in part be mediated by modulation of AR expression. PMID- 1457127 TI - Cell cycle-dependent localization of immunoreactive basic fibroblast growth factor to cytoplasm and nucleus of isolated ovine fetal growth plate chondrocytes. AB - Basic fibroblast growth factor (basic FGF) is a potent mitogen for chondrocytes in vitro and is present in developing cartilage in vivo. Studies of intracellular basic FGF localization in other cell types have revealed a transient nuclear presence. We have examined ovine fetal growth plate chondrocytes for the presence of intracellular basic FGF by immunocytochemistry. Chondrocytes were isolated from the proximal tibial growth plate of lamb fetuses between 75 and 80 days' gestation using collagenase, and were cultured in monolayer before use between passages 3 and 6. In non-synchronized cell cultures 58 +/- 6% of cells (mean +/- s.d., n = 3) demonstrated cytoplasmic staining for immunoreactive basic FGF. Of these cells, 18 +/- 3% also exhibited strong nuclear staining. Chondrocytes were growth-restricted and restarted into the cell cycle with 2% (vol/vol) fetal calf serum. The timing of S phase was followed by nuclear labelling of nuclei with [3H] thymidine followed by autoradiography, or by the incorporation of [3H] thymidine into trichloroacetic acid-precipitable DNA in parallel cultures. A cytoplasmic presence of immunoreactive basic FGF did not appear, following immunocytochemistry, until the second half of G1 with 97% of cells immunopositive 2 hr prior to S phase. Nuclear staining for basic FGF appeared 2 hr before peak nuclear labelling index, and 56% of cell nuclei were immunopositive. Following entry into S phase cytoplasmic and nuclear basic FGF immunostaining rapidly disappeared. When these experiments were repeated with or without the presence of anti-basic FGF antibody or heparin, the presence of the antibody significantly reduced peak [3H] thymidine incorporation into DNA during S phase while exposure to heparin increased this. However, the proportion of cells demonstrating cytoplasmic or nuclear staining for immunoreactive basic FGF, and the time of onset of staining, were unaltered. Incubation of cells with suramin blocked subsequent DNA synthesis and no intracellular basic FGF was visualized. Cell conditioned culture medium, extracellular matrix and cytoplasm from synchronized cultures of chondrocytes were taken at time points throughout the cell cycle and assessed for basic FGF content by radioimmunoassay. Basic FGF was detectable in each compartment and steadily rose throughout the second half of G1 to reach maximum values around the S phase. The accumulation of basic FGF in medium, matrix and cytoplasm was blocked by the presence of cycloheximide.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1457129 TI - [Fibrinolytic therapy in thrombosis of the main arteries]. AB - Fibrinolytic therapy (FLT) was applied in 79 patients, aged from 37 to 76 years, suffering from thromboses of the main arteries of the pelvis and lower extremities. The duration of the disease ranged from one day to 8 months. FLT was conducted with streptokinase preparations: streptodekase, avelysin, and celiase. FLT lasted 24 hours on average (from 7 hours to 3 days depending on the duration of the disease). The main blood flow in the affected arterial segment was completely restored in 49 (62%) patients. In 30 (38%) cases attempts to restore the blood flow failed. The affected extremity was amputated in 4 patients. Severe hemorrhagic complications occurred in 4%., small subcutaneous hematomas in 14.4%, fragmentation of thrombi with the development of distal embolism in 7.6% of cases, anaphylactic shock developed in one patient. Four patients died. PMID- 1457130 TI - [Adjuvant laser angioplasty: is it beneficial?]. PMID- 1457128 TI - Identification of bone morphogenetic protein-2 in early Xenopus laevis embryos. AB - Polyclonal antibodies capable of reacting with amphibian bone morphogenetic protein (BMP-2 and -4) were raised in rabbits by immunization with a synthetic 21 amino acid peptide which corresponds to a sequence residing in the mature protein of Xenopus BMP-2 (xBMP-2). The antibodies recognized an embryonic BMP as well as mammalian and bacteria expressed recombinant xBMPs. The antibodies detected, under reducing conditions, a 30 kDa protein in the extract of oocytes and embryos during early development. Interestingly, acidification of the extract from each developmental stage yielded a protein band of smaller molecular weight of 18 kDa, which is similar in size to reduced form of mature BMPs purified from mammalian species. Two-dimensional electrophoresis employed to examine the molecular weight of unreduced forms using the antibody, revealed that both molecular forms are monomeric in the embryos. The result suggests that at least BMP-2 mRNA previously detected in early embryos, is translated into peptide but the dimerization may be incomplete or strictly limited in these embryos. PMID- 1457131 TI - [Surgical treatment of supraventricular tachyarrhythmias using laser]. AB - Much importance is attached lately to the use of lasers in surgical treatment of tachyarrhythmias. The advantages of the laser radiation are as follows: the possibility of using it on a contracting heart, its exact and selective effect, infliction of even damages in preservation of the structure, reduction of damage to the myocardium as a whole. At the Bakulev Institute of Cardiovascular Surgery, USSR AMS, 52 operations were carried out in the management of supraventricular tachyarrhythmias by laser radiation: 27 operations for laser isolation of the atrioventricular node, 15 operations for laser isolation of the atria and bases of the pulmonary veins (11 in combination with laser isolation of the atrioventricular node), 3 operations for ablation of ectopic foci in the atria and ventricles, 4 operations for ablation of the bundle of His, and 3 operations for removal of Maheim's nodoventricular tract. Among the patients who were operated on, 12 had atrial flutter, 21--atrial fibrillation, 11--paroxysmal atrioventricular nodal tachycardia, 5--ectopic supraventricular tachycardia, and 3 patients had paroxysmal tachycardia due to the presence of Maheim's nodoventricular tract. The method of laser isolation of the atrioventricular node was developed. It is performed on a working heart under conditions of normothermal extracorporeal circulation by Nd-YAG laser radiation under electrophysiological control. Antegrade conductivity was reduced to 420-510 msec. Among 56 patients who underwent operation 39 had sinus rhythm, 10 had Degree II III block, and 7 patients had a recurrence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457132 TI - [Intraoperative transesophageal echocardiography in diagnosing left atrial thrombosis in patients with mitral valve disease]. AB - Intraoperative transesophageal echocardiography was conducted in 63 patients with various cardiosurgical pathology (mitral stenosis--43, combined mitral valvular disease--3, mitral incompetence--10, combined mitral-aortal valvular disease--8). Thrombosis of the left atrium was diagnosed in 13 patients. Transesophageal echocardiography in 38 patients revealed spontaneous echo-contrasting of blood currents in the cavity of the left atrium. Statistical analysis showed this sign to be characteristic of mitral stenosis complicated by thrombosis of the left atrium (p < 0.001). Transesophageal echocardiography allows visualization of thrombi of small diameter (1.0-1.5 cm). Specificity of the method is 100%, sensitivity 87%. PMID- 1457133 TI - [Correction of dyslipidemia in patients with arteriosclerosis obliterans as a method for improving the results of endovascular angioplasty]. AB - The authors analyse the results of endovascular angioplasty of the pelvic and lower limb arteries in 147 patients of various age suffering from arteriosclerosis obliterans. It was found that the results of endovascular angioplasty depended on the state of the lipid balance. The necessity for correcting the shifts in the lipid metabolism is shown. The article evaluates the results of dyslipidemia correction by dietotherapy, pharmacotherapy, and operation for partial ilio-shunting in patients with arteriosclerosis obliterans of the pelvic and lower limb arteries. The efficacy of the listed methods of treatment are analysed according to the severity of dyslipidemia. PMID- 1457134 TI - [Radionuclide evaluation of myocardial perfusion in patients who had undergone cardiomyoplasty]. PMID- 1457135 TI - [Current view of sclerotherapy for varicose veins of the legs]. PMID- 1457136 TI - [The use of isosorbide dinitrate during open heart surgery]. PMID- 1457137 TI - [Changes in the functional state of patients after radical correction of tetralogy of Fallot]. AB - The authors studied the changes in the functional condition of patients in the immediate and long-term periods after radical correction of Fallot's tetralogy. The values of the heart pumping and contractile functions at rest and during bicycle ergometer exercise were studied by tetrapolar chest rheography; oxygen consumption was studied by spirometry. Thirty patients were examined in the early postoperative period and then 6 and 12 months after the operation. The values were compared with those in healthy children. It is shown that 12 months after the operation the clinical condition improves, the physical capacity for work increases, and the exercise response is more adequate. Adequacy of the correction of the anomaly is the main determinant of the patients' functional condition by this time. PMID- 1457138 TI - [Possibilities of using plasma flow in lung surgery]. AB - Experiments on 10 mongrel dogs demonstrated the efficacy and reliability of argon plasma flux in achieving hemo- and aerostasis in surgical debridement of gunshot wounds of the chest "Fakel" plasma surgical complexes were used as a source of plasma. A total of 43 operations were performed on patients whose ages ranged from 16 to 68 years: pulmonectomy 3, lobectomy 24, bilobectomy 4, atypical resection of the lung 4, pleurectomy with lung decortication 5, diagnostic thoracotomy 2, rib resection 1. Argon plasma flux was used in thoracotomy, treatment of wound surfaces of the lungs and pleura, separation of the interlobar fissures, and division of the main and lobar bronchi. The plasma flux produced an analgesic effect; as a result much less narcotics and analgesics were needed and physical activity was permitted earlier. The amount of discharge from the pleural cavity along the drain was 1.5-2 times less (200 +/- 40 ml) as compared to that in the traditional methods for conducting similar operations. No complications associated with application of plasma flux were noted. Incompetence of the bronchial stump, rethoracotomy for bleeding or suppuration were not encountered. PMID- 1457139 TI - [Effect of subtotal resection of costal cartilage on the basic chest dimensions in children with funnel chest deformity]. AB - The paper summarizes the results of anthropometric and computed tomographic studies of the external and internal chest dimensions in 86 patients with Degree II-III infundibuliform chest deformity. Full resection of deformed cartilages of the third to seventh ribs has been examined for its impact. The children with infundibuliform chest deformity have been found to have an impressed anteroposterior dimension of the bilateral chest. The transversal and anteroposterior dimensions of the chest remain unchanged after removal of cartilages. The chest enlarges only sagittaly. One- and three-year follow-ups have indicated that full removal of the deformed cartilage has no impact on the growth of the chest. PMID- 1457140 TI - [External respiratory function in children with bilateral, chronic, nonspecific inflammatory disease of the lungs after surgical treatment]. AB - The results of operative treatment of children with bilateral chronic unspecific inflammatory diseases of the lungs were studied in follow-up periods of up to 17 years. Among the 73 patients studied, 19 had a history of bilateral and the remaining a history of unilateral resections. According to the findings of respiratory function examination, a combined type of ventilation disorders with mild hypoxemia and hypercapnia was characteristic of this group of patients before the operation. In the postoperative period the restrictive syndrome intensifies because the volume loss is not compensated for. There is a discrepancy between the clinical and functional data in evaluation of the results of the operation. However, in cases of good clinical results after extensive resections of the lungs a positive dynamics of the ventilation capacity of the lungs with increased oxygen tension in the arterial blood is recorded. PMID- 1457141 TI - [Correction of valvular insufficiency in chronic venous diseases of the lower extremities]. PMID- 1457142 TI - [Successful prosthetic replacement of the pulmonary trunk during correction of tetralogy of Fallot in a child one year and 11 months old]. PMID- 1457143 TI - [Intra-coronary thrombolytic therapy and direct myocardial revascularization in the treatment of acute myocardial infarction (experience at the A.N. Bakulev Institute of Cardiovascular Surgery)]. PMID- 1457144 TI - [Multiple injury of the interventricular septum in closed chest trauma]. PMID- 1457145 TI - [A case of surgical treatment in giant aneurysm of the right internal carotid artery]. PMID- 1457146 TI - [Successful treatment of infected post-traumatic arteriovenous aneurysms of the neck]. PMID- 1457147 TI - [Aorto-coronary and mammary-coronary bypass of the working heart without extracorporeal circulation in patients with ischemic heart disease and a history of two or more myocardial infarctions]. AB - The paper shows how successfully surgical myocardial revascularization can be performed on the working heart without applying extracorporeal circulation in 17 patients with a history of two or more myocardial infarctions. Deaths were not observed among the patients operated on. The follow-ups of the patients were 1-2 months. PMID- 1457148 TI - Management of patients with schizophrenia in general practice. PMID- 1457149 TI - Desktop laboratory technology for general practice. PMID- 1457150 TI - Why do patients consult the general practitioner? Determinants of their decision. AB - In order to obtain more information about the reasons why patients consult their general practitioner 1000 patients completed a questionnaire in the waiting rooms of eight general practices. After the consultation the patients received a second questionnaire. The aim of the study was to determine why people decide to consult their general practitioner about one complaint but not about a second complaint. Both questionnaires were based on the health belief model, augmented by three other factors: the perceptions patients have of their own abilities to cope with their condition (efficacy of self care), their knowledge about the complaint and their need for information. The results showed that two of the additional factors (efficacy of self care and need for information) as well as most of the factors of the health belief model (efficacy of general practitioner care, perceived severity of complaint and cues to consult) were important determinants of consulting the general practitioner. The results suggest that patients sometimes expect information from their general practitioner rather than medical treatment. Furthermore, as the perceived efficacy of general practitioner care is also an important determinant, unnecessary consultation or unnecessary delay in treatment could be prevented by offering patients information about the potential effectiveness of medical care or self care for specific conditions. Implications for general practitioners' daily practice and future research are discussed. PMID- 1457151 TI - Comparison of the use of four desktop analysers in six urban general practices. AB - There is little data on the advantages and disadvantages of using desktop analysers in general practice. This prospective trial compared four of the analysers available in the United Kingdom, in six urban general practices, over a six month period. Of the 2619 tests where the time was noted, 55.8% were performed outside the hours when routine transport to a hospital laboratory was possible (after 12.00 hours). Of the 3530 tests performed the commonest were measurements of cholesterol (14.4 tests per 5000 patients per 30 days), glucose (6.0 tests) and haemoglobin (5.6 tests). Less than 5% of the tests were performed as an emergency despite the speed at which results are available. The main reasons for requesting the tests were screening or case finding (56.9%), with the remainder for monitoring chronic disease, especially diabetes and hypercholesterolaemia. There was evidence that the use of the machines in the four practices reduced requests for hospital laboratory blood tests by 24-40% of pre-study levels. However, there was a considerable increase in testing for cholesterol (three fold) and haemoglobin (eight fold) on the desktop analysers, compared with the number of laboratory tests requested before the study. The cost per test of using such machines is closely related to the level of activity and probably does not compete favourably with hospital testing unless several tests are performed each day. Quality control tests were within the specified limits on at least 98% of occasions, however these tests also identified the need for laboratory back up where a problem was found. PMID- 1457152 TI - Attitudes to community psychiatry among urban and rural general practitioners. AB - General practitioners' requirements for community psychiatric services may differ according to the area in which they practise. A questionnaire survey of general practitioners' attitudes to community psychiatric services is reported from three contrasting areas: an inner city urban area, a new town and a rural area. General practitioners in all areas wanted more consultation with psychiatrists, and 53 68% wanted regular psychiatric outpatient clinics in their surgeries. There was enthusiasm for community psychiatric nurses and for help with psychotherapy. In the rural area general practitioners favoured surgery based psychiatric outpatient clinics and arranging emergency hospital admissions themselves; in urban areas domiciliary visits from psychiatrists to help with emergencies were favoured. These results appear to reflect the greater geographical distance between primary and hospital based secondary care in rural as opposed to urban areas. Overall, general practitioners wanted more support from community psychiatric services in carrying out their primary therapeutic role especially in rural areas far from hospital-based psychiatric services. PMID- 1457153 TI - Study of patients who chose private health care for treatment. AB - A questionnaire survey was carried out in 1991 in Wessex regional health authority of a sample of private patients having inpatient treatment in eight independent hospitals, and in pay beds in three National Health Service hospitals. A total of 649 patients replied (response rate 60.7%). Sixty respondents to the questionnaire were also interviewed. The aim of the study was to discover which groups of people chose private care rather than using the NHS, and why. In view of the current emphasis on consumerism in health care, the study also aimed to examine how patients exercised choice in a market situation and how well informed they were when they did so. The questionnaire asked about the role and influence of the general practitioner in patients' decisions to use private health care for treatment. The largest group of respondents were in the 36-50 years age group (34.2%). Of the respondents 59.9% were women, 54.1% were in social class 2 and 77.3% were married or cohabiting. The most common reason for using private health care for treatment was to avoid NHS waiting lists (61.5% of respondents) although they did not necessarily know how long that wait would have been. Patients sought their general practitioner's opinion about whether to use private health care in 187 cases (28.8%). The majority of the 649 patients (71.2%) had decided to use private health care before consulting the general practitioner. However, patients were influenced by their general practitioner's advice on the choice of consultant and choice of hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457154 TI - Diagnostic yield from barium enemas: a study among patients referred by general practitioners and hospital outpatient departments. AB - Although the double contrast barium enema is the standard radiological examination of the colon, it is not universally available to patients referred by their general practitioners. A retrospective survey of all double contrast barium enemas carried out over a two year period in one health district was undertaken to determine the diagnostic yield of pathological findings for patients referred by general practitioners and hospital outpatient departments and for patients who had rigid sigmoidoscopy prior to the enema and those who did not. A total of 530 patients were studied. The diagnostic yield for the hospital outpatients was 41.6% and in the general practitioner group 35.6%. In the patients who had rigid sigmoidoscopy the yield was 42.7% compared with 32.6% in those who had no prior sigmoidoscopy. It is concluded that the withdrawal of direct access for barium enemas to general practitioner patients in this district because of a low diagnostic yield cannot be justified. The lower diagnostic yield in the patients who did not have sigmoidoscopy supports the policy of requiring this examination prior to all barium enemas. PMID- 1457155 TI - Audit and academic departments of general practice: a survey in the United Kingdom and Eire. AB - A questionnaire and telephone survey was carried out in April 1991 of all 31 academic departments of general practice in the United Kingdom and Eire; 30 departments responded. The aim of the study was to assess the departments' level of involvement in teaching about audit in the undergraduate curriculum, their role in the development of audit in primary care including involvement with medical audit advisory groups, whether they undertook teaching about audit to other health professionals and whether they were involved in audit related research. Eleven of 27 responding undergraduate departments provided formal teaching about audit and five intended to introduce it in the near future. Respondents expressed concerns about teaching audit to undergraduates, including lack of time in the curriculum, difficulties making the teaching relevant and interesting, and a lack of expertise and knowledge of the subject among the staff. All 29 departments in the UK were represented on medical audit advisory groups, and audit related research was being carried out in 24 undergraduate departments. The role of academic departments of general practice in the development of audit in primary care is discussed. PMID- 1457156 TI - Abnormal cervical smear test results: old dilemmas and new directions. AB - Primary care professionals play a major role in the cervical screening programme in the United Kingdom, especially since the new contract for general practitioners. Many aspects of the programme are still the subject of broad debate and detailed research. New policies regarding the programme are generated at various levels; feedback is not always made directly available to primary care teams. This review article attempts to summarize the current available literature on cervical screening, focusing on the meaning of minor degrees of dysplasia, cervical cancer in younger women, the role of the wart virus, frequency of smear tests, diagnosis and treatment, counselling, and concludes with practical advice to help the practice team. PMID- 1457157 TI - Paternalism and the doctor-patient relationship in general practice. AB - This paper is a brief introduction to the subject of paternalism as it occurs in general practice. A definition of paternalism is provided and the four main types of doctor-patient relationship within the paternalistic spectrum are described. These relationships are illustrated with examples from general practice. Some of the extensive literature on paternalism is reviewed. It is concluded that paternalism is rarely justified when treating patients of sound mind and then only where restoration of the patients' autonomy is the main aim. PMID- 1457158 TI - The College in my faculty. PMID- 1457159 TI - Cancer scare in general practice. PMID- 1457160 TI - Nitrite test for bacteriuria detection. PMID- 1457161 TI - Computer generated discharge summaries. PMID- 1457162 TI - General practice research. PMID- 1457164 TI - Telephone consultations. PMID- 1457163 TI - GP referrals for x-ray examination. PMID- 1457165 TI - Admission times for patients with myocardial infarct. PMID- 1457166 TI - GP working style and patient health status. PMID- 1457167 TI - Long term follow up of women who have had gestational diabetes. PMID- 1457168 TI - The case for a primary health care authority. PMID- 1457169 TI - A survey of links between mental health professionals and general practice in six district health authorities. AB - The aim of this study was to obtain an estimate of the extent to which collaborative schemes exist between general practice and mental health professionals and to assess the influence of practice size and district on these schemes. A questionnaire asking about such links was sent to each general practice in six randomly selected health districts in England. The response rate was 75%. Half of the 261 responding practices had a link with a community psychiatric nurse, 21% with a social worker, 17% with a counsellor, 15% with a clinical psychologist and 16% with a psychiatrist. Practices with more general practitioners were significantly more likely to have a link with a counsellor, after allowing for marked differences between the sizes of practices in the different districts. There was a tendency for some practices to have many links, while others had few. This poses questions about the efficiency and equity of collaborative schemes in primary care. Further research is required to investigate the quality of these links and the extent to which they serve the interests of the patient. PMID- 1457170 TI - Drug consumption during the first 18 months of life of infants from smoking and non-smoking families. AB - In a geographically well defined population in southern Sweden, a study was made of the overall consumption of drugs by infants during their first 18 months of life. The study population comprised 240 infants, of whom 90 were from families where tobacco was smoked by one or both parents and 150 were from non-smoking families. The investigation was carried out retrospectively by interviewing the mothers at the routine 18-month check up at the child health clinic, combined with study of the medical records at the district health centre, and at the paediatric and ear, nose and throat departments of the nearby hospital. In addition, the reliability of the interview method compared with review of medical records was investigated. Particular attention was paid to the consumption of antibiotics and the relationship between 'passive smoking' and consumption of antibiotics necessitated by respiratory tract infections. There was widespread use of both prescribed and non-prescription remedies. At the age of 18 months, about two thirds of all infants in the area had been prescribed an antibiotic (or other antibacterial agent) on at least one occasion. Infants from smoking families had been prescribed significantly more antibiotics than had infants from non-smoking families. The same pattern was also apparent for nose drops and dimethicone/dicyclomine hydrochloride. The incidence of respiratory tract infections requiring antibiotic treatment was higher in infants from smoking families than from non-smoking families in all the three-month age groups up to 15 months. The responses to the retrospective interview accorded closely with the details recorded in the medical records.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457171 TI - Morbidity in early childhood: differences between girls and boys under 10 years old. AB - The aim of the study was to investigate the differences in presented morbidity and use of health services among boys and girls in early childhood. The study was performed using data collected by the continuous morbidity registration project of the department of general practice at Nijmegen University. All recorded morbidity, referrals to specialists and admissions to hospitals were recorded by the registration project. The study population included children born in four practices from 1971 to 1984. The children were followed up until the age of five years and if possible until the age of 10 years. The morbidity of the children had been categorized into three levels of seriousness of diagnosis and 15 diagnostic groups as part of the registration project. Boys presented more morbidity than girls in the first years of their lives. For the age group 0-4 years this was true for all levels of seriousness of diagnosis except the most serious. In this younger age group significantly more boys than girls suffered respiratory diseases, behaviour disorders, gastroenteritis and accidents. Girls suffered from more episodes of urinary infection than boys in both age groups. More boys were referred to specialists and admitted to hospital than girls. The findings of this study suggest that not only inborn factors can explain the sex differences in presented morbidity and use of health services in early childhood. In particular, differences between girls and boys in terms of non-serious morbidity and referral and admission rates suggest a different way of handling health problems in boys and girls in early childhood both by parents and doctors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457172 TI - Systematic care of diabetic patients in one general practice: how much does it cost? AB - This study examines the costs of running a method of systematic care for diabetic patients in one general practice--the monthly 'diabetic day'. Doctor, nurse, chiropodist, dietitian, clerical officer, building and stationery costs were included in the evaluation. The study took place in an inner city practice of seven partners based in a health centre. The cost per year of running the diabetic days was 1854.53 pounds to the practice and 4465.69 pounds to the National Health Service (1989 prices). The cost to the practice included family health services authority reimbursements and excluded the cost of the chiropodist and dietitian. The cost per attendance was 38.17 pounds to the NHS and 15.85 pounds to the practice while the cost per patient per year was 58.00 pounds to the NHS and 24.08 pounds to the practice. The practice suffered a net loss after taking into account health promotion clinic payments received from the family health services authority. The cost to the NHS of each attendance at the practice was considerably greater than estimates of the cost of attendance at the outpatients department of a local trust hospital. However, it is argued that general practice has an essential role in the improvement of diabetic surveillance, and that an adequate remuneration package could transform the care of many patients with diabetes. PMID- 1457173 TI - Pre-recorded answerphone messages: influence on patients' feelings and behaviour in out of hours requests for visits. AB - The aim of this qualitative study was to investigate the feelings and behaviour of patients requesting out of hours visits on hearing pre-recorded answerphone messages. Actual messages which had been recorded were classified by a group of four people. Examples of each type of message were then played to a second group, of six people, who expressed their feelings about the varying messages. A third group, of 10 people, was asked to invent hypothetical emergency situations of increasing severity. For each of the emergency situations their proposed actions on hearing the different types of answerphone message were recorded. The results showed that people preferred short messages telling them what to do in an emergency and the time of the next surgery. They also felt that the message should be recorded by a doctor and not a receptionist and be delivered in a 'neutral' tone. Proposed actions were not influenced by the content of the message or the person recording the message. The most important factor in deciding which action to take was the tone of the message. A 'strict' rather than a 'neutral' tone tended to discourage patients from calling out their doctor and was more likely to lead to inappropriate responses. It is suggested that answerphone messages recorded by the doctor, stating what to do in an emergency and the time of the next surgery, delivered in a neutral rather than a strict tone, will lead to the most appropriate responses from patients. PMID- 1457174 TI - Risk factors for coronary heart disease: a study in inner London. AB - A survey was carried out among 281 men and women aged between 30 and 64 years randomly selected from five general practices located in the inner London borough of Tower Hamlets, to determine the prevalence of risk factors for coronary heart disease. Smoking and obesity were both more pronounced in Tower Hamlets than in comparable national studies: 51% of men and 44% of women were smokers and 57% of these were smoking 20 or more cigarettes per day. A body mass index of 30 or more was present in 18% of men and 10% of women and a body mass index of 25 or more in 71% of men and 49% of women. Two or more risk factors for coronary heart disease (smoking and/or hypertension and/or raised cholesterol levels) were present in 25% of men and 22% of women. For every person known by their general practitioner to have established cardiovascular disease, there were an additional two people also at risk on the basis of multiple risk factors. In this inner city population the prevalence of cardiovascular risk, for women as well as men, has major resource and organizational implications for primary care. A strategy for change requires action based on graded multiple risks for both men and women. PMID- 1457176 TI - Involvement of lay visitors in general practice assessment visits. AB - Six practice assessment visits which jointly involved lay and medical visitors were arranged by the patient liaison group of the Royal College of General Practitioners. These visits were inspired by the 'What sort of doctor' report published by the RCGP in 1985. A subgroup of the patient liaison group adapted the assessment grid from the report to take account of involving lay visitors with doctors on practice visits. The visits were educationally valuable to the lay visitors, and also prompted some practical changes in the practices. This experiment might have further application in the development of fellowship by assessment or even in the process of reaccreditation of general practitioners. PMID- 1457175 TI - Improving mental health through primary care. AB - The government white paper Health of the nation has highlighted mental health as a key issue for the next decade. Primary care is being encouraged to take a leading role in developing effective services for people with mental health problems. This paper reviews current research on key aspects of mental health in adults: the prevalence of mental health problems, improving detection and management of mental health problems, the role of counselling, and communication between primary and secondary care. Recommendations are made for initiatives in both research and service development. PMID- 1457177 TI - All that is solid melts into air--the implications of community based undergraduate medical education. PMID- 1457178 TI - Postcoital contraception. PMID- 1457179 TI - Mood variability in asthmatic patients: a case report. PMID- 1457180 TI - Rare case of autoinoculation of orf. PMID- 1457181 TI - Primary ciliary dyskinesia. PMID- 1457182 TI - Acute herpes zoster, postherpetic neuralgia, acyclovir and amitriptyline. PMID- 1457183 TI - Curettage and cautery of skin conditions. PMID- 1457184 TI - Video recorded consultations and fellowship by assessment. PMID- 1457185 TI - On the historical origins of HIV-1 (MN) and (RF). PMID- 1457186 TI - The dilemma of AIDS vaccine and therapy. Possible clues from comparative pathogenesis with measles. AB - AIDS viruses, because of their unique properties, are extraordinary. Past successes achieved with vaccines against ordinary viruses do not provide the guidelines needed to develop successful vaccines against HIV. Neither vaccines nor drugs can be relied upon to provide an answer to AIDS. AIDS is a disease of immune dysfunction and destruction, and an alternative to prevention of infection or cure might lie with elimination of the clinical consequences of infection. This might find a basis in precise definition of its pathogenesis. The enormity of possible pathogenetic changes in HIV infection invites simplification, and might be aided by a search for clues among ordinary viruses in which there is a less complicated biology and spontaneous recovery from infection. Measles virus infection presents analogies to AIDS, especially in the induction of anergy and increased mortality, in the long term, from diseases other than measles as observed in children infected during early life. This was demonstrated recently in increased deaths, all causes, during a three-year period among infants who were given live measles virus vaccine of high infectivity titer during early infancy, sometimes in the presence of maternal antibody. AIDS and measles may be diseases of similar pathogenesis, but with the difference that AIDS immunopathology is progressive while that for measles is regressive. PMID- 1457187 TI - HIV-1 tropism: truth or consequences? PMID- 1457188 TI - Value of HIV transmembrane glycoprotein oligomers as target antigens in early detection of anti-env antibodies: a retraction. PMID- 1457189 TI - Kaposi's sarcoma: a review of gene expression and ultrastructure of KS spindle cells in vivo. AB - The ultrastructural features and the gene expression pattern of Kaposi's sarcoma (KS) spindle cells in vivo suggest that KS is a tumor of the mixed cell type. The expression pattern of cytokines and cytokine receptors in the tumor lesion, together with the results obtained from in vitro characterization of KS-derived cells, provide evidence that paracrine mechanisms of growth factor action are important for the maintenance of KS. The reports on virus infection of KS cells suggest an indirect role of virus infection in the induction of KS, most likely mediated by immunostimulation and subsequent production of cytokines. PMID- 1457190 TI - The control of the antibody isotype response to recombinant human immunodeficiency virus gp120 antigen by adjuvants. AB - Both saponin and muramyl dipeptide (MDP) formulated with a squalane-in-water emulsion of large particle size prepared with a vortex mixer were superior to Al(OH)3 as adjuvants for HIV gp120 in mice. All the adjuvants induced IgG1 antibody, but saponin elicited the highest titers of IgG2a. The secretion of interleukin-5 (IL-5) and interferon gamma (IFN gamma) by lymph node cells cultured in vitro with gp120 was studied. All the cultures secreted IL-5, but only those from saponin-immunized mice produced IFN gamma, suggesting that saponin is capable of activating both the Th1 and TH2 T-cell subsets. The titers of neutralizing antibodies were low with both MDP and saponin, and they occurred in mice which were also positive for antibodies against a V3 loop peptide. Glucosaminylmuramyl dipeptide (GMDP) which is less pyrogenic than MDP and a nonpyrogenic analog GMDPA, displayed equivalent adjuvant activity to MDP. The level and isotype composition of antibodies induced by GMDP in combination with squalane emulsions depended on the dimension of the emulsion particles. With a large (2500 nm) particle size the response was confined to IgG1 in Balb/c mice, but when this was reduced to 150 nm by sonication the antibody response was increased and relatively high levels of IgG2a appeared in some mice. PMID- 1457191 TI - Serum IgA subclasses and molecular forms in HIV infection: selective increases in monomer and apparent restriction of the antibody response to IgA1 antibodies mainly directed at env glycoproteins. AB - In a study population representing different CDC stages of HIV infection, 58% exhibited IgA hypergammaglobulinemia resulting from proportional increases in both the IgA1 and the IgA2 subclasses. These increases were detected early in infection, did not correlate with CD4 count, and remained elevated throughout disease progression. Absolute concentrations of polymeric IgA present within each subclass were unchanged, indicating that increased production of monomeric IgA1 and IgA2 were responsible for elevations of total IgA. These elevations were not completely attributable to a specific antibody response to viral infection, since Western blot analysis of purified IgA samples indicated that HIV-reactive IgA antibodies could be demonstrated only within the IgA1 subclass. Dominating IgA1 anti-HIV responses were also observed in two secretory IgA samples isolated from colostrum of healthy HIV seropositive mothers, suggesting that a similar isotype restriction exists in the mucosal IgA compartment. The binding of IgA1 to HIV proteins contrasted markedly to that observed with identical concentrations of IgG purified from the sera of the same patients. While IgG reacted more intensely and broadly with all HIV proteins, IgA1 antibodies were directed predominantly against envelope glycoproteins. In many patients, a total lack of IgA1 reactivity to gag and pol proteins was accompanied by intact IgG responses to these same antigens. Though all IgA samples examined reacted with HIV, fewer responses to gp160, gp120, and p24 were observed in samples from AIDS and AIDS-related complex (ARC) patients, suggesting a declining titer of IgA antibodies against these antigens may be associated with disease progression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457192 TI - HIV-1 matrix protein p17 resides in cell nuclei in association with genomic RNA. AB - We have shown previously that HIV-1 matrix protein p17 is transported to the nucleus of Jurkat-tat and H9 cells soon after infection. As shown in this combination, gag polyprotein p55 synthesized 48 h after cell infection is cleaved in cytosol rapidly after its synthesis, and nascent p17 enters the nuclei and gradually accumulates there. Uncleaved p55 molecules and intermediate precursors are rapidly transported to the membranes and are also found in nuclei. Mature gag proteins are seen in membranes only after prolonged period of labelling or chase (4 or more hours later). To determine whether the nascent p17 is associated with viral genomic RNA in the nuclei, the cells were fractionated, the viral complexes were immunoprecipitated by monoclonal antibodies (MAbs) against gag proteins, and RNA was extracted and analyzed by slot and blot hybridization. MAb against p17 precipitated all the viral RNA from the nuclei including full-size genomic RNA and essential parts from membranes while MAb against p24 did not precipitate any viral RNA from the nuclei. These data suggest that matrix protein is linked to genomic RNA in the nuclei and raise the possibility that p17 may transfer viral nucleocapsids from the nuclei to plasma membranes, the site of virus assembly. PMID- 1457193 TI - Genetic and functional analysis of a set of HIV-1 envelope genes obtained from biological clones with varying syncytium-inducing capacities. AB - To study HIV-1 envelope-mediated syncytium formation we have amplified, cloned, expressed, and sequenced individual envelope genes from a set of eight biological HIV-1 clones. These clones were obtained from two patients and display either a syncytium-inducing (SI) or nonsyncytium-inducing (NSI) phenotype. Upon expression through recombinant vaccinia virus, individual envelope gene products display heterogeneous syncytium-inducing capacities which reflect the phenotype of the parental biological HIV-1 clones in all cases. For the eight biological HIV-1 clones presented here, variation of the envelope gene alone is sufficient to explain the observed variable syncytium-inducing capacity of the respective parental viruses. In addition we determined the complete nucleotide sequence of these envelope genes. The predicted amino acid sequence revealed a considerable amount of variation located mainly in the previously denominated variable regions. In various regions of envelope genes obtained from the same patient, phenotype associated amino acid variation was found. This phenotype associated amino acid variation however, is not conserved between the two sets of envelope genes derived from different patients. Four envelope sequences derived from clones obtained from one patient showed phenotype-associated amino acid variation in the fusion domain. Sequencing of 12 additional fusion domains revealed that this same variation is found in four additional clones. However, a functional test performed on recombinant vaccinia expressing mutant envelope genes showed that this observed fusion domain variation does not contribute to the variation in syncytium-inducing capacity of the envelope gene product. PMID- 1457194 TI - HIV-1-induced cytopathogenicity in cell culture despite very decreased amounts of fusion-competent viral glycoprotein. AB - In order to examine the potential role of env-induced membrane fusion in the cytopathogenic properties of HIV-1 in cell culture, the effects of mutations within the proteolytic cleavage site of gp160, which result in a reduction but not a complete absence of proteolytic processing have been further studied. Cells expressing the mutant glycoproteins were shown to be severely reduced in their capacity to form syncytia. However, viruses encoding these glycoproteins could infect cell culture cells, albeit with delayed kinetics, and, at late infection time points, resulted in complete cytolysis of the infected culture. Since amplification by polymerase chain reaction and direct sequencing of the DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA, this shows that the amount of fusion competent viral glycoprotein does not influence HIV-1 cytopathogenicity, but rather that other parameters must be involved in inducing cell death. PMID- 1457195 TI - Properties of HIV membrane reconstituted from its recombinant gp160 envelope glycoprotein. AB - Human immunodeficiency virus (HIV) membrane has been reconstituted from the recombinant envelope glycoprotein precursor (gp160) by a detergent dialysis technique. Electron microscopy shows that gp160-virosomes are spherical vesicles with a mean diameter identical to that of viral particles. Enzyme-linked immunosorbent assay and immunogold labeling demonstrate efficient association of gp160 with lipid vesicles and proteolysis treatment reveals an asymmetric insertion with about 90% of glycoproteins having their gp120-moiety pointing outside. Glycoproteins are organized as dimers and tetramers and gp160 retains its ability to specifically bind CD4 receptor after reconstitution into virosome. PMID- 1457196 TI - Relevance of the quantitative detection of HIV proviral sequences in PBMC of infected individuals. AB - Changes in HIV replication during progression of HIV infection were assessed by estimation of the number of peripheral blood mononuclear cells (PBMC) harboring HIV proviral sequences. Samples from 23 patients at different stages of HIV infection were analyzed by quantitative polymerase chain reaction (PCR) using GAG primers. HIV titers in PBMC were also determined by serial dilutions of cells in coculture with phytohemagglutinin-activated normal PBMC. A positive correlation was observed between the number of HIV DNA copies and the HIV titer in PBMC. The PCR test was more sensitive than the coculture technique. The number of HIV copies detected by PCR ranged from 50 to 10,500 per 10(6) PBMC: assuming one copy per cell this implies a frequency of proviral HIV-containing cells of one per 100 to one per 20,000 mononuclear cells. The mean number of HIV DNA sequences in PBMC was significantly lower in asymptomatic patients than in AIDS patients and patients with AIDS-related complex (ARC). In patients who progressed from asymptomatic infection to AIDS, the number of HIV DNA copies in PBMC rose, indicating an increase of HIV replication. These results show that the number of infected PBMC increases during clinical progression. However, some asymptomatic patients had a higher number of HIV DNA copies in their PBMCs suggesting that increased HIV replication precedes the appearance of clinical symptoms. PMID- 1457198 TI - Areas of sequence homology between several staphylococcal exotoxin "superantigens" and the HIV-1 pol protein. PMID- 1457197 TI - On the historical origins of HIV-1 (MN) and (RF). PMID- 1457199 TI - Weight of HIV. PMID- 1457200 TI - Signature pattern analysis: a method for assessing viral sequence relatedness. AB - Signature pattern analysis identifies particular sites in amino acid or nucleic acid alignments of variable sequences that are distinctly representative of a query set of sequences relative to a background set. We explore the merits of using signature patterns for analysis of HIV-1 (human immunodeficiency virus type 1) sequences in cases of epidemiological linkage and potential superinfection. For these purposes, query sets are viral sequences that are all derived from one HIV-1 infected individual, hence the signature pattern is the array of sites that are characteristic of the range of viral variants obtained from that person. Once a signature pattern has been objectively defined, it can be used to examine other viral sequences from other individuals for evidence of genetic relatedness. A computer program to facilitate this analysis, VESPA, is described and applied to sequence data gathered during the investigation of HIV-1 transmission in a dental practice. The implications of signature polymorphisms seen within an infected individual, and shared polymorphisms between linked individuals, are also considered. VESPA may also be applied to the molecular analysis of biological phenotypes. PMID- 1457201 TI - Convergent evolution in the homology between HIV gp160 and HLA class II molecules. PMID- 1457202 TI - Interaction of human immunodeficiency virus with human macrovascular endothelial cells in vitro. PMID- 1457203 TI - Conserved structural features in the interaction between retroviral surface and transmembrane glycoproteins? AB - Among the retroviruses, the surface (SU) and transmembrane (TM) glycoproteins of lentiviruses are linked exclusively by noncovalent bonds. For some C-type retroviruses, however, a small proportion of the SU proteins has been shown to be linked to their TM proteins by a disulfide bond, with the remainder being noncovalently associated. A region near the carboxyl terminus of the HIV-1 SU glycoprotein has been implicated in contacting the TM glycoprotein. Computer modelling indicates that this region of divergent lentivirus and oncovirus SU glycoproteins forms a structurally conserved "pocket" which could accommodate a "knob"-like protrusion formed by an immunodominant region in the TM protein containing the CxxxxxC (lentiviruses) or CxxxxxxCC (C- and D-type viruses) motif. An anti-idiotypic monoclonal antibody, raised against a monoclonal antibody reacting with a sequence in the "pocket" of HIV-1 gp120, was found to bind to synthetic peptides close to the CxxxxxC motif. It is suggested that part of the SU-TM linkage mechanism for the lentiviruses and oncoviruses is a 'knob and socket' structure and that the interaction between SU and TM proteins is similar in one region for lentiviruses and C-type as well as D-type viruses. The conserved knob and socket linkage may be relevant to a mechanism for viral-cell membrane fusion that is broadly common to all of these retroviruses. PMID- 1457204 TI - Unusual amino acid sequence of the second Ig-like domain of the feline CD4 protein. AB - We have cloned and sequenced the cDNA for cat CD4. The overall amino-acid sequence of cat CD4 is similar to that from the primate and rodent CD4 molecules, with a 58% identity between the cat and human sequences. Comparison to the crystal structure of human CD4 does, however, reveal unusual features in the second Ig-like domain, D2, of cat CD4. First, a reciprocal substitution between a tryptophan and a cysteine, this latter involved in an intrasheet disulfide bond of human D2, is predicted to generate an intrastrand disulfide bond, a feature rarely observed in an Ig-fold. Second, a large serine-threonine-rich insertion is found between the A and B beta strands of D2. This sequence is a potential O linked glycosylation site, and should protrude in a region that appears flexible in human CD4. This unusual insertion could affect the interaction of cat CD4 with class II molecules, or with FIV, a feline homolog of HIV. The expression of cat CD4 in different environment, or of a mutated human CD4 carrying the cat insertion, should help in understanding the role of cat CD4 as a putative receptor for FIV, and the CD4/MHC class II interaction. PMID- 1457205 TI - LFA-1 adhesion molecules are not involved in the early stages of HIV-1 env mediated cell membrane fusion. AB - A recently developed sensitive assay to examine the early stages of HIV-1 env mediated cell fusion is based on the redistribution of fluorescent dyes between membranes and cytoplasm of adjacent cells, monitored by fluorescence video microscopy. This assay demonstrated that membrane fusion can occur under conditions where no syncytia are formed. Fusion started earlier than syncytia formation and was not very sensitive to HIV-1 env+/CD4+ cell ratios. In the current study, this assay was used to determine the role of LFA-1 in HIV-1 env mediated membrane fusion and syncytia formation. CD4- LFA-1- Epstein-Barr virus transformed lines from two leukocyte adhesion deficiency patients were infected with recombinant vaccinia expressing gp120/41 (HIV-IIIB), and cocultured with CD4+ subclones of the human T cell line CEM, which were generated by chemical mutagenesis and express either normal (LFA-1+), or low levels of LFA-1 (LFA-1lo). It was found that the LFA-1lo T-cell clone formed much smaller and fewer syncytia compared to the LFA-1+ subclones, but both clones fused equally well with the gp120/41 expressing LFA-1- B cells as monitored by redistribution of fluorescent dyes. Furthermore, monoclonal antibodies against the LFA-1 molecules reduced the number of syncytia formed but had no effect on membrane fusion. These findings demonstrate that the adhesion molecule LFA-1 does not play a crucial role in the early events of HIV-1 env-mediated cell membrane fusion, but may contribute to the later events leading to giant cell formation. PMID- 1457206 TI - Sulfated polyester interactions with the CD4 molecule and with the third variable loop domain (v3) of gp120 are chemically distinct. AB - Sulfated polyesters (SP) that inhibit HIV infection interact with both the gp120 binding region of CD4 molecules and with the v3 domain loop of gp120 molecules (gp120/v3) but the contributions of these interactions to the inhibition of HIV env-mediated fusion are presently unclear. In order to characterize the molecular mechanisms by which SP inhibit HIV env-mediated fusion, we studied the effect of SP treatment on env-mediated fusion of CD4+ cells driven by recombinant vaccinia virus (vPE-16) and on the binding of anti-HIV MAbs to cellular gp120 or purified, rgp120. SP were more effective than neutralizing anti-gp120/v3 MAbs in inhibiting env-mediated fusion. In addition, SP interacted with the v3 loop of gp120 to inhibit the binding of the neutralizing MAb 9284 but not the binding of 9305, a neutralizing anti-gp120/v3 MAb that binds to an adjacent epitope. Because SP are polyanions, we compared the chemical properties of the SP-gp120/v3 and SP-CD4 interactions. Whereas the ability of SP to inhibit the binding of MAb 9284 and rgp120 was relatively independent of NaCl concentrations, the ability of SP to interfere with rCD4-rgp120 binding depended on the NaCl concentration and was maximal at low NaCl concentrations. In addition, the SP-gp120 interaction was found to be reversible, in contrast to the SP-rCD4 interaction which was previously shown to be relatively irreversible at low salt. These data are consistent with the notions that the interaction of SP with CD4 is primarily electrostatic, but that the interaction of SP with gp120 has complex characteristics that implicate a role for protein conformation. PMID- 1457207 TI - Studies on the role of the V3 loop in human immunodeficiency virus type 1 envelope glycoprotein function. AB - Mutations within the principal neutralizing determinant (the V3 loop) of the HIV 1 surface envelope glycoprotein gp120 block or greatly reduce the ability of the HIV-1 envelope glycoprotein to induce cell fusion in CD4+ HeLa T4 cells while keeping its CD4 binding ability. However, when either cysteine or both cysteines forming the V3 disulfide bridge were mutated, the resultant glycoprotein could not mediate cell fusion, undergo proteolytic processing, or bind CD4. To investigate the role that the V3 loop plays in gp160 processing and CD4 binding, we deleted the entire V3 loop region of the HIV-1 env gene. The resultant glycoprotein could not mediate cell fusion in the HeLa T4 cell line and no proteolytic processing of gp160 or CD4 binding could be detected. To test whether any domain of the V3 loop is involved in attaining the proper envelope glycoprotein conformation required for proteolytic processing and CD4 binding, we introduced a series of deletions into the coding region of the V3 loop. Most of the residues within the V3 loop could be removed while retaining gp160 processing and CD4 binding. Our results indicate that the cysteines that form the V3 loop or the disulfide bond itself are important for proper envelope glycoprotein folding and processing. Because many of the mutants constructed in this study do not contain the type-specific neutralizing determinant of HIV-1, they may be potential reagents to bind group-specific neutralizing antibodies or to elicit a group-specific neutralizing response against HIV-1. PMID- 1457208 TI - Analysis of the envelope region of the highly divergent HIV-2ALT isolate extends the known range of variability within the primate immunodeficiency viruses. AB - HIV-2ALT is a highly divergent HIV-2-related isolate that is genetically equidistant to the prototypic HIV-2 strains, defined by HIV-2ROD, and to the simian immunodeficiency viruses SIVmac and SIVsm. We have now cloned and sequenced the envelope region of HIV-2ALT, thus completing the analysis of the whole viral genome. The sequences of env and nef and of the second exons of tat and rev were compared with those of the other viruses of the HIV-2/SIVsm/SIVmac group. Despite of the high degree of variation of HIV-2ALT, functional domains of the genes are conserved. Although in env, the overall pattern of constant and variable domains is maintained, many single amino acid exchanges exist at positions previously thought to be constant in HIV-2 strains. In addition, when compared with a broader spectrum of immunodeficiency viruses, which includes SIVMND from mandrill and SIVAGM from African green monkey, HIV-2ALT Env has a high percentage of amino acid exchanges, which are unique to this strain. This underlines the separate branch of HIV-2ALT within the phylogenetic tree and makes obvious the inclusion of such divergent strains in preventive and therapeutic programs. PMID- 1457209 TI - Infection of rhesus and cynomolgus macaques with a rapidly fatal SIV (SIVSMM/PBj) isolate from sooty mangabeys. AB - A variant of simian immunodeficiency virus (SIVSMM/PBj), isolated from a chronically infected pig-tailed macaque has been shown in previous studies to produce acutely fatal disease uniformly in pig-tailed macaques and in some rhesus macaques. The present study extends investigation of SIVSMM/PBj pathogenesis in rhesus and cynomolgus monkeys. Cynomolgus and rhesus macaques were found to be uniformly susceptible to infection, but as previously reported, the rhesus were found to not be uniform in their response during the acute disease. Homogenized tissues from a rhesus that died acutely from SIVSMM/PBj were passaged to 6 rhesus monkeys in an attempt to increase lethality. Five of 6 rhesus monkeys receiving intravenous inoculation of either spleen (10(3) TCID50) or lymph node (10(5) TCID50) homogenate developed acute disease; 4 died (days 8-10), 1 recovered, and one rhesus remained asymptomatic. Three of 3 cynomolgus macaques and 4 of 4 pig tailed macaques receiving the same inoculum died acutely within 9 days. Clinical disease in macaques that died was characterized by diffuse lymphadenopathy within 5 days of inoculation and severe diarrhea beginning 1 to 3 days before death. Anorexia, lymphopenia (< 1000 cells/mm3), and mild hypoalbuminemia preceded onset of diarrhea by 24 h. Viral p27 was detected in circulation by day 6 postinfection, with all animals dying acutely having detectable serum p27 and no detectable humoral response. Acute lethality was attributed to severe metabolic acidosis (pH < 7.20) which was observed 24-48 h prior to death in the pig-tailed and cynomolgus macaques. Immunohistochemistry revealed numerous SIV antigen positive lymphocytes and macrophages in the lymph nodes, spleen, gut-associated lymphoid tissues and gastrointestinal lamina propria. Histopathologic lesions included marked to severe hyperplasia of the T-cell-dependent areas in lymphoid tissues and diffuse nonulcerative lymphohistiocytic gastroenteritis. Surviving rhesus developed strong humoral immune responses to the major SIV proteins. PMID- 1457210 TI - Detection of anti-human cell antibodies in sera from macaques immunized with whole inactivated virus. AB - More than 200 sera from macaques immunized with several different vaccine preparations were tested in various assays with cells of human and macaque origin. Only in instances where whole inactivated SIV preparations were used for immunization, were reactivities found with normal human cells, and this was the case in every instance. Such sera produced a marked clumping of several normal human cell lines and exhibited strong staining of the cell surface in FACS analysis. In the presence of SIVDeltaB670, these sera also enhanced infectivity and fusion formation. When similar tests were performed with macaque cells as targets, such phenomena were not easily discernible. Likewise, there was no trace of such activities in sera from normal animals, animals chronically infected with SIV, or in those from animals which received recombinant viral subunits as vaccines. Finally, we show that in several instances where whole inactivated virus was used as a vaccine, there is a strong correlation between the titer of anticellular activity with protection. PMID- 1457211 TI - Analysis of HIV-1 envelope mutants and pseudotyping of replication-defective HIV 1 vectors by genetic complementation. AB - Infectious HIV-1 particles containing replication-defective vectors that express the hygromycin B phosphotransferase gene were generated by transient complementation in COS-1 cells. A defective vector dependent only on trans complementation with an env gene and a small vector containing a deletion of almost all of the trans region were used to examine pseudotyping of HIV-1 by an amphotropic murine retrovirus. Although pseudotyping by the heterologous envelope glycoprotein occurred with efficiency, no pseudotyping at the RNA level was observed. Genetic complementation was used to rapidly analyze the effect of env mutations in the V3, proteolytic processing site, fusion domain, and cytoplasmic tail on viral infectivity. Mutations decreasing syncytium formation usually also lowered infectivity. However, a mutation in the cytoplasmic tail and a separate mutation adjacent to the fusion domain dramatically decreased viral particle infectivity but did not appreciably decrease envelope glycoprotein-mediated cell to-cell fusion. These results may indicate that these regions of the transmembrane peptide are necessary for acquisition of envelope glycoprotein by budding virus particles or for virus entry. PMID- 1457212 TI - Differential tropism of clinical HIV-1 isolates for primary monocytes and promonocytic cell lines. AB - Previously we demonstrated a correlation between a nonsyncytium-inducing (NSI), non-T-cell line tropic phenotype of HIV-1 isolates and the capacity to replicate in primary monocyte-derived macrophages (MDM). Here we demonstrate that these NSI, monocytotropic HIV-1 isolates lack the capacity to replicate in two promonocytic cell-lines, HL60 and U937. In contrast, most syncytium-inducing (SI) HIV-1 isolates with tropism for T-cell lines and generally non-monocytotropic were able to establish a productive infection in promonocytic cell lines. Similar differences in tropism for monocytes and promonocytic cell lines were observed with infectious molecular clones. Our results indicate that virological studies on promonocytic cell lines do not necessarily pertain to the HIV-1 infection of monocytes in vivo. PMID- 1457213 TI - HIV-1 infection of the trophoblast cell line BeWo: a study of virus uptake. AB - An in vitro model has made it possible to demonstrate HIV transmission from infected lymphocytes to placental trophoblast cells via endocytosis. Upon addition to cultured trophoblast cells (BeWo), chronically HIV-infected lymphocytic cells (MOLT-4) adhered to the epithelial cells via a complex of newly induced microvilli. Though viruses were infrequently seen in the infected lymphocytic cell line, mature virions appeared promptly and profusely in the interstices between the interdigitating microvilli of the two cell types. Virions appeared to bud from the lymphocyte donor cells at the point of cell-to-cell contact and were rapidly taken up by the trophoblast cells via an endocytic mechanism involving coated pits, endosomes, and lysosomes. Electron microscopic observations suggest that HIV may later escape into the trophoblast cytoplasm by fusing with the endosome membrane or by lysing the lysosome membrane. Coincubation for 1 h was sufficient to establish HIV infection in the trophoblast cell line. Four weeks after thoroughly washing out the donor lymphocytic cells, HIV RNA was demonstrated in clusters of BeWo cells by in situ hybridization, and p24 antigen was localized with immunocytochemistry. Soluble CD4 did not block infection as measured by p24 ELISA. The HIV infection was productive and chronic as demonstrated by cocultivating the BeWo cells with indicator lymphocytes 4 weeks after the initial infection. This study, demonstrating a mechanism of HIV transmission, expands upon previous observations that trophoblast cell lines lacking the CD4 viral receptor can nevertheless be infected by HIV and can support productive infection. PMID- 1457214 TI - Modulation of glucocorticoid binding to rat liver cytosol receptor by lipid soluble extracts from the serum of AIDS patients. AB - The total liposoluble extract of sera from AIDS patients, IVC1 and IVD stages, containing cortisol and free fatty acids (FFA) inhibited [3H]dexamethasone binding to a lesser extent than did the same quantity of total liposoluble extract of sera from healthy men. FFA isolated from extracts of AIDS sera by Sephadex LH20 chromatography had less effect on [3H]dexamethasone binding to rat liver glucocorticoid receptor than those extracted from sera of healthy men. These results suggest the presence in sera of AIDS patients of a liposoluble substance which could be limiting the inhibitory effect of FFA on [3H]dexamethasone binding to glucocorticoid receptor by inducing a conformational change in glucocorticoid receptor that could alter the biological action of glucocorticoids. The pathological consequence could be the apparent contradiction of high cortisolemia and clinical symptoms of adrenal insufficiency that have been observed in AIDS patients. PMID- 1457215 TI - Dendritic cells from patients with tropical spastic paraparesis are infected with HTLV-1 and stimulate autologous lymphocyte proliferation. AB - Dendritic cells (DC), important antigen-presenting cells for recruiting T cells into immune responses, are susceptible to infection with HIV-1 and this can cause either stimulatory or suppressive effects on T cells. We examined another human retrovirus, HTLV-1, to determine whether DC were infected and caused any changes in T-cell function. Patients infected with HTLV-1 who have tropical spastic paraparesis (TSP) show high 'spontaneous' lymphocyte proliferation. We studied the basis for this by analyzing the interactions in vitro between lymphocytes and antigen-presenting cells and compared cells taken from HTLV-1-positive TSP patients with those taken from HTLV-1-positive healthy carriers and HTLV-1 negative family members. In HTLV-1-positive individuals, 0.4-5.1% of the DC were infected with HTLV-1 as determined by in situ hybridisation. In TSP patients, depletion of DC and purification of T cells abolished 'spontaneous' lymphocyte proliferation. Reinstating the DC, but not B cells or macrophages, restored proliferation, an effect that was blocked by antibodies either to class II major histocompatibility antigens or to HTLV-1 itself. Thus, presentation of HTLV-1 antigens by infected DC to autologous T cells could result in the abnormal T-cell proliferation and cause the inflammatory reaction leading to tissue damage in TSP. We also speculate that persistent infection of DC with HTLV-1 and consequent continuous stimulation of T cells might be instrumental in the development of HTLV-1-mediated T-cell leukemia. PMID- 1457216 TI - Dysregulation of adult T-cell leukemia-derived factor (ADF)/thioredoxin in HIV infection: loss of ADF high-producer cells in lymphoid tissues of AIDS patients. AB - Adult T-cell leukemia (ATL)-derived factor (ADF) is a multifunctional protein homologous to thioredoxin (TRX) with co-cytokine and thiol-dependent reducing activities. ADF/thioredoxin production is enhanced in T cells transformed by HTLV I. We have examined the effect of HIV-1 infection on ADF/TRX expression using specific antibody against ADF/TRX. Lymph nodes from 5 AIDS and 1 AIDS-related complex (ARC) patients were examined. As a control, 8 HIV noninfected lymph nodes, including 3 cases with hyperplasia, were also examined. Immunohistopathological studies using normal HIV noninfected lymph nodes showed that ADF/TRX high-producer (ADFh) cells were macrophages and cells with dendritic morphology in the paracortical area. Abundant ADFh cells were observed in HIV noninfected hyperplastic lymph nodes. The number of ADFh cells was low in hyperplastic lymph nodes from an ARC patient. All of the lymph nodes of 5 AIDS cases were atrophic and the number of ADFh cells were extremely low. To verify these histochemical studies, we examined the effect of in vitro HIV infection on ADF/TRX expression in HTLV-I (+) T-cell lines. Western blot analysis showed that a reduction of ADF/TRX in HIV-1-infected SKT-1B and MT-2 cells, and the reduction inversely correlated with p24 antigen level. On the basis of the above in vivo and in vitro findings, we imply that the levels of ADF/TRX were down-regulated by HIV-1 infection and that the down-regulation may play a role for pathophysiology of HIV-infected individuals. PMID- 1457217 TI - Characterization of oxyphenarsine as a potential antiviral agent for AIDS. AB - The historical antisyphilis drug oxyphenarsine has been tested for antiviral activity and for cytotoxicity to characterize it as a potential therapy for treatment of HIV infections. These data show that the compound demonstrates marginal antiviral activity against the HTLV-IIIB strain of HIV-1, two clinical isolates of HIV-1 (one sensitive to AZT and one resistant), and the MS strain of HIV-2. However, treatment with concentrations of oxyphenarsine showing optimal anti-HIV activity resulted in significant cytotoxicity. The drug's selectivity index was not significantly improved when tested against H9 cells chronically infected with the HTLV-IIIB strain of HIV-1. Thus, despite a previous report suggesting significant antiviral activity and low cytotoxicity for oxyphenarsine, the data presented here do not provide support for further development of this drug as an anti-HIV agent. PMID- 1457218 TI - Rapid complementation assay for anti-HIV-1 drug screening and analysis of envelope protein function. AB - A complementation assay is described that can be used with relative safety to quantitate rapidly inhibitory effects of potential anti-HIV-1 drugs on virtually any stage of the HIV-1 life cycle by measurements of chloramphenicol acetyltransferase (CAT) activity. Of particular interest is that this system is also capable of detecting inhibition of the viral trans-activator Rev, an important potential target for drug intervention. Other applications of the system may include studies to identify domains of the envelope glycoprotein that determine infectivity and tropism or that define epitopes recognized by neutralization antibodies. PMID- 1457219 TI - Rapid and simple characterization of in vivo HIV-1 sequences using solid-phase direct sequencing. AB - Solid-phase direct sequencing was used to obtain in vivo sequence data of polymerase chain reaction (PCR)-amplified HIV-1 p25/p7 gene segments. The solid phase sequencing method was compared to double-strand sequencing of preparative gel electrophoresis-purified amplification products and found to give more consistent results. Lysates of cells were compared to purified DNA as PCR template. HIV-1 sequences were as well amplified from lysates as from purified DNA and 7,780 bp of sequence from 41 samples were produced by direct sequencing. Sequence analysis revealed common sequence motifs relating the sequence to the Euroamerican and African groups of sequences previously described. The results indicate that many viruses of diverse origin circulate in Finland, although the majority seems to be of Euroamerican type. Solid-phase direct sequencing may provide a valuable tool for both epidemiological and pathogenic studies of in vivo HIV-1 infections. PMID- 1457220 TI - Hospice and hope: an incompatible duo. PMID- 1457221 TI - Regulations vs. ideals: a case history of a hospice closure. AB - The cost of health care and health insurance and the increasing number of Americans without access to basic health services has become a primary issue in today's society. Leading politicians, economists, planners, and private individuals recognize the essential need to re-design the system and provide coverage to all Americans. However, the history of programs strangling in the red tape created by inflexible regulatory efforts to set standards, monitor performance, and control costs, thereby denying access to individuals they were specifically designed to serve, points to the need for an equally new approach to planning such a system. The authors have attempted to illustrate, through the case history of the closure of a hospice serving a poor socioeconomic area of New York City, the need for government regulators, program planners, and caregivers to recognize and define common goals and develop flexible and cooperative working relationships. PMID- 1457222 TI - Two nursing study tours. PMID- 1457223 TI - Terminal care in primary care postgraduate medical education programs: a national survey. PMID- 1457224 TI - What is a non-profit hospice? PMID- 1457225 TI - Cancer pain management. How are we doing? PMID- 1457226 TI - Imagination: the lost art. PMID- 1457227 TI - The last few days. AB - In the dying patient, coma is preceded by either progressive sedation or the development of the organic brain syndrome of delirium. More than one-third of dying patients experience some difficulties during the last 48 hours of life with noisy and moist breathing, pain, and agitation and restlessness the most common. The great majority of these terminal symptoms can be managed by reassurance or drug intervention. Sublingual lorazepam and continuous subcutaneous infusion of midazolam can be effective in controlling terminal restlessness. PMID- 1457228 TI - Preparing for the death of a loved one. PMID- 1457229 TI - Music dying. PMID- 1457230 TI - Knowing what death and the process of dying is all about. PMID- 1457231 TI - Her 68-year old face was wrinkled, emaciated and jaundiced. PMID- 1457232 TI - Hospice research: the importance of program participation. AB - Hospice research is needed in order to understand the complex phenomena of holistic care for terminally ill persons and their families. Hospice program participation is key to future hospice research efforts. The purpose of this article is to encourage hospice programs to participate in hospice research. The discussion includes why research is done, who undertakes a research project, the role of institutional review boards in assuring rights of human subjects and potential strategies for recruitment of research subjects. The authors use their experiences with conducting hospice research to illustrate potential recruitment strategies. PMID- 1457233 TI - Acupressure wrist bands to relieve nausea and vomiting in hospice patients: do they work? AB - This study assessed the effects of acupressure wrist bands on the nausea and vomiting of terminally ill patients. Using a single subject experimental design, six hospice patients were exposed to three conditions: An acupressure wrist band; A placebo wrist band; A no wrist band condition. Patients and their caregivers rated nausea and vomiting during the treatment. Despite some difficulty obtaining complete data, the results of this preliminary test indicate that acupressure wrist bands were not effective in reducing nausea and vomiting in this small sample of hospice patients. PMID- 1457234 TI - Family assessment and its relation to hospice care. AB - It is proposed that a family system evaluation be added to the initial medical and social history used during a hospice assessment. The family evaluation should assess the family through a functional/dysfunctional framework in addition to assessing the role structure of each of its members. This additional data can offer insight into the internal workings of the family while adding important information as to the compliance level of the family in accepting hospice and the services that hospice has to offer. This may assist in not only the quality of service implementation but in assisting hospice personnel in lessening their potential for stress and burnout as well. PMID- 1457235 TI - The trials and tribulations of software customization for a small volunteer hospice. PMID- 1457236 TI - New routes of opiate administration. PMID- 1457237 TI - Board wars. PMID- 1457238 TI - The hospice volunteer: a person of hospitality. AB - Volunteers are integral members of the hospice interdisciplinary team. They are distinguished from other members of the team only by role, not by expectation. The distinction is not between "volunteer" and "professional," because every team member is to be professional in the best sense of that word. If a distinction is to be made, it is that some hospice staff members are salaried while others donate their services. Volunteer staff members are expected to be as responsible and accountable as every other member of the team. ALL staff members must realize the importance of taking care of personal needs in order to be able to care for others. Even though the following article deals primarily with the volunteer hospice staff member, the points outlined can just as easily be applied to the salaried staff member. PMID- 1457239 TI - Hospice and mainstream medicine. PMID- 1457240 TI - Alzheimer's disease. PMID- 1457241 TI - Hospice care coast to coast. PMID- 1457242 TI - Camp Jamie. PMID- 1457243 TI - Perceptions of the most helpful nursing behaviors in a home-care hospice setting: caregivers and nurses. AB - The purpose of this study was to determine those nursing behaviors perceived as most helpful and least helpful by primary caregivers and by hospice nurses in a home-care hospice setting. A Q-sort of 60 nursing behaviors ranked from most to least helpful was completed by 20 caregivers, during the bereavement period and by five hospice nurses, who were currently employed by the hospice. These nursing behaviors were categorized as: Nursing behaviors related to the patient's physical needs; nursing behaviors related to the patient's psychosocial needs; and nursing behaviors related to the psychosocial needs of the caregivers. PMID- 1457244 TI - Keeping the mission. PMID- 1457245 TI - International Hospice Institute; Academy of Hospice Physicians--a vision for hospice. PMID- 1457246 TI - A consensus statement by radiation oncologists regarding radiotherapy for bone metastases. PMID- 1457247 TI - Functional morphology of the enteric nervous system with special reference to large mammals. AB - This short review reports the latest insights into the structural organization of the enteric nervous system, with special emphasis on the intrinsic innervation of the intestinal tract of large omnivorous mammals such as the pig. Using various techniques, including lesion experiments, morphological and neurochemical features of distinct neuronal populations as well as the direction of the axonal processes within the different nerve networks could be revealed. Special attention was paid to the considerable species differences in this respect between large omnivorous animals and humans on the one hand and small laboratory animals on the other hand. PMID- 1457248 TI - Histogenesis, structure and relationships of interstitial cells of Cajal (ICC): from morphology to functional interpretation. AB - Interstitial cells of Cajal (ICC) have been found exclusively in gut muscle coat, occupying an interstitial position between nerve endings (NE) and smooth muscle cells (SMC). Light microscope stainings of ICC are aspecific and useful only for evidentiating cell body and ramifications strictly intermingled with SMC and nerve fibers. Transmission electron microscope investigation, on the contrary, permits unequivocable identification and detailed description of ICC cytology. The ultrastructural findings have led to consider ICC as a new cell type, with a specific cytology, highly smooth muscle-like. Specialized ICC relationships with surrounding cells have been found, suggesting the existence of an anatomical unit made up of three closely interconnected elements: the NE-ICC-SMC units. The time of this unit appearance and the steps of its cell types cytodifferentiation from foetal to adult life differ according each gut level. A region-specific ICC distribution inside the gut muscle coat and peculiar organizations of ICC surrounding connective tissue have been observed. On these morphological bases an ICC pacemaking role has been suggested. Recordings of spontaneously generated slow waves from some ICC seemed to confirm this role. According to this hypothesis, smooth muscle contraction should be dependent on ICC function and smooth muscle relaxation on inhibitory nerves release. Further morpho-functional investigations and correlations of obtained data are still necessary in order to better clarify the ICC role and its influence or dependence on both nerve and muscle tissues inside each gut level. The identification of the neurotransmitters contained in the NE contacting ICC and/or SMC needs to be pursued. PMID- 1457249 TI - The European Microwave Club. PMID- 1457250 TI - Microwave-stimulated decalcification of compact bones. PMID- 1457251 TI - Demonstration of a rapid immunoalkaline phosphatase-complex labeling technique (APAAP) using microwave irradiation on hematological blood smears. PMID- 1457252 TI - Incidence and clinical study of ectopic erythropoiesis in adult patients with thalassemia intermedia. AB - We carried out total body computerized tomography (CT) studies and examined the retrospective clinical data of 29 adult patients with thalassemia intermedia (TI) to evaluate the incidence, features and pathogenesis of ectopic erythropoiesis (EE), located chiefly at the paravertebral gutters in the thorax, was present in 65.5% of the patients; 15% of them had severe clinical complications. We found a clear relationship between EE development and early presentation age of thalassemia, splenectomy and the presence of 100% fetal hemoglobin. The frequent occurrence of EE suggests that CT screening of patients with thalassemia intermedia should be mandatory. We also recommend radiotherapy as a preventive measure for the clinical complications of thalassemic patients with EE. PMID- 1457253 TI - [Acromegalic cardiopathy: a morphofunctional study with color-Doppler echocardiography]. AB - We used color-Doppler echocardiography in an investigation of cardiac morphology and function to verify the cardiac anatomic and functional changes in acromegalic patients with or without hypertension and hyperlipemic states. Fifteen patients with growth hormone-secreting pituitary adenoma (mean age: 47.9 years) and 15 healthy control subjects were studied. We measured serum growth hormone (GH), somatomedin-C, cholesterol, triglyceride levels and carried out echocardiographic studies of the following cardiac morpho-functional parameters: left ventricular diameter, volume, mass and wall systolic stress. Serum GH and somatomedin-C levels were significantly higher in acromegalic patients than in controls (p < 0.001 and p < 0.001 respectively). Echocardiography evidenced increased left ventricular mass (60% of the acromegalic patients; p < 0.05) and increased wall systolic stress (53.3%; p < 0.05). Color-Doppler analysis evidenced abnormal diastolic function in 8 acromegalic patients (p < 0.001). We thus conclude that the most characteristic feature of acromegalic heart disease is left ventricular involvement, diastolic dysfunction, increased left ventricular mass or wall systolic stress. The pathogenesis is most probably multifactorial: essential hypertension, associated with slow and progressive evolution of heart disease, appears to be a determining factor. PMID- 1457254 TI - [The immunopathogenesis of hepatitis B]. AB - Knowledge of hepatitis B immunopathogenesis has greatly improved in the last few years thanks to the development of new methods of lymphocyte culture and the introduction of molecular techniques in the study of the cell-mediated antiviral immune responses. Some of the immune mechanisms likely responsible for liver cell injury and viral clearance during hepatitis B have recently been characterized. By using synthetic peptides and high efficiency recombinant expression vectors. HLA class I restricted cytotoxic T cells specifically able to recognize the nucleocapsid antigen of the hepatitis B virus (HBV) have been isolated from the blood of patients with acute self-limited hepatitis B. The observation that this cytotoxic response is lacking or very weak in chronic patients who do not succeed in clearing the virus suggests a major role for cytotoxic T cells in terminating virus infection. Similar behaviour is shown by HLA class II restricted CD4+ T cells which express much stronger levels of response to HBV nucleocapsid antigens in acute than in chronic HBV infection. Whether these defective responses in chronic patients are due to an actual lesion of the host's immune system or to viral mutations affecting immune surveillance and thereby allowing virus escape, still remain open issues. A definitive answer to these questions will, we hope, provide the appropriate tools to devise effective immune therapies against chronic HBV infection. PMID- 1457255 TI - [Diabetic nephropathy and arterial hypertension: the physiopathological aspects and antihypertensive treatment]. AB - The purpose of our review is to delineate the pathogenic steps linking arterial hypertension in diabetes to diabetic nephropathy. The results of recent studies suggest that arterial hypertension in diabetes might lay a decisive pathogenetic role in the evolution of diabetic nephropathy: the existence of a higher ratio of erythrocytic Na/Li counter-transport in nephropathic diabetics as well as higher pressure values in the parents of diabetics who develop nephropathy indicates that hypertension may be casually related to renal complications. Diabetes associated hypertension involves the modification of two important pressure- regulation factors: 1. an alteration in extracellular volume and increased renal absorption of sodium which leads to an expanded pool; 2. increased cardiovascular reactivity to norepinephrine and angiotensin II, an effect which might be related to increased intracellular calcium. Hyperfiltration seems to be present at the onset of diabetes, and arterial hypertension increases the transglomerular pressure gradient which is thought to play an important role in the pathogenesis of kidney damage. Antihypertensive drugs such as ACE-inhibitors and calcium channel blockers tend to protect the regulation of renal function. This could be explained by the fact that ACE-inhibitors suppress the trophic effects of angiotensin II on the nephron, while calcium channel blockers might interfere with intracellular processes involved in cell hypertrophy that require the interaction of calcium ions. In the management of diabetes prevention of diabetic nephropathy requires early and careful correction of diabetes-associated hypertension. We discuss the major groups of antihypertensive drugs, their metabolic side-effects and intrarenal induced hemodynamic changes. PMID- 1457256 TI - [Ascites, oligoanuria and macrohematuria]. PMID- 1457257 TI - [Chronic eosinophilic pulmonitis with eosinophilic pleurisy. A report on 2 clinical cases seen by the authors]. AB - We discuss the cases of two patients affected with chronic eosinophilic pneumonia (CEP) pleurisy and eosinophilia in pleural effusion, not previously mentioned in the literature, to point out their peculiarity, to consider differential diagnosis and the effect of steroid therapy. Both patients, a 57-year-old man and a 55-year-old woman, were atopic: they had been suffering from allergic rhinitis and asthma for several years when they suffered sudden onset of cough, dyspnea and thoracic pain. This symptomatology persisted for more than 6 weeks. Chest radiography highlighted pulmonary infiltrates, not fixed in the first case, fixed in the second. The laboratory features revealed eosinophilia in peripheral blood and in pleural effusion. These data conformed to the criteria suggested by Jederlinic et al. for the diagnosis of chronic eosinophilic pneumonia. Tuberculosis had been present in the remote history of the second case; the repeated research for mycobacteria was negative, and no improvement was seen after antitubercular chemotherapy for one month. We excluded the diagnosis of allergic bronchopulmonary aspergillosis because of the absence of both precipitating antibodies against Aspergillus fumigatus and bronchiectasis. Neither vasculitis nor autoantibodies were found; possible drug-related correlations were excluded; culture data and serological researches for infections were negative in both cases; no involvement of other districts correlated to hypereosinophilia was evidenced. Clinical and radiological remission was obtained in both cases after steroid therapy for a month at the dosage of 1-2 mg/kg daily. No clinical recurrence was seen during a follow-up period of 6 months. Pleural effusion has already been reported in patients with CEP, while we have not found any references to pleural fluid eosinophilia in this disease; this finding has instead been already reported in patients affected with acute eosinophilic pneumonia or hypereosinophilic syndrome. PMID- 1457258 TI - [Thrombosis of the superior sagittal sinus and ulcerative colitis. A case report]. AB - We describe a rare case of superior sagittal sinus thrombosis in a young man (26 years) with undiagnosed ulcerative colitis. The patient was hospitalized with headache and paresis of the right arm and leg. he had had rectal bleeding and diarrhea for the previous 4 weeks. Despite the fact that heparin therapy is still considered controversial, we successfully treated our patient with low doses of sub-cutaneous heparin. He did not suffer any side-effect. PMID- 1457259 TI - Intracholecystic hemorrhage: an atypical complication after liver needle biopsy. AB - The authors report an unusual case of intracholecystic hemorrhage related to liver biopsy in a 23-year-old man. Echography and computed tomography evidenced changes in density within the gallbladder which were probably caused by hemorrhagic discharge. Although the mechanism by which liver biopsy induced intracholecystic hemorrhage is unclear, the authors believe that this iatrogenic complication was probably the result of microlesions of the gallbladder wall caused by needle puncture: the lesions extended into the submucosa and provoked slow hematic leakage. The pain syndrome began 48 hours after biopsy. The peculiarity of this case report was confirmed by the fact that no bile was aspirated, no choleperitoneum was found, and no gallbladder tissue was detected in the sample. The authors conclude by recommending clinical and echographic control following liver biopsy. PMID- 1457260 TI - Diethylcarbamazine in the treatment of patients with onchocerciasis. PMID- 1457261 TI - The use of microcomputer-based psychomotor tests for the evaluation of benzodiazepine effects on human performance: a review with emphasis on temazepam. AB - 1. The literature relating to the effects of benzodiazepines in general, and temazepam in particular, on human psychomotor performance as assessed using microcomputer-based testing batteries is surveyed. 2. The adverse effects of central nervous system depressants on performance is an important mediocolegal issue and frequently comes into question in on-the-road and on-the-job accidents. The use of microcomputer-based testing batteries allows for performance evaluation both in the laboratory and at-the-scene, as well as providing the opportunity to model a large number of different behaviours required in routine yet complex psychomotor tasks. 3. The conclusions in general are: (1) The benzodiazepines as a class of drugs impair both cognitive and motor performance. These effects are often subtle when low doses are involved or when testing occurs the morning following evening administration of the medication. (2) No single psychomotor task adequately simulates complex daily tasks such as automobile driving. A battery of tests that evaluates a number of the components of such tasks is necessary to determine adequately the full range of effects of these medications. PMID- 1457262 TI - New models of focal cerebral ischaemia. AB - 1. Studies in animal models of stroke have provided an invaluable contribution to our current understanding of the pathogenesis of cerebral ischaemia. The strengths of stroke research in animals are: 1) the ability to control the severity, duration, location and cause of the ischaemia, variables which confound interpretation of human stroke data; 2) co-existent disease states and variations in cerebrovascular anatomy are avoided; and 3) physiological parameters such as blood pressure, blood gases, temperature and plasma glucose (all of which influence the magnitude of the ischaemic lesion) can be closely monitored and controlled. Taking all these things on board, it is possible to induce a consistent focal ischaemic lesion in animal models of stroke (e.g. the permanent occlusion of the middle cerebral artery (MCA) in the rat). This has resulted in the wide use of animal models for assessment of anti-ischaemic drug efficacy as well as for research into the pathophysiological sequelae of stroke. 2. Traditionally focal ischaemia models involved permanent occlusion of a major cerebral artery such as the MCA. However, since vessel occlusion is seldom permanent in human stroke more recent developments have incorporated reperfusion (following ischaemia) into the design of the animal model. This has been achieved by reversible occlusion of cerebral vessels using 1) intraluminal filaments; 2) microclips; 3) the abluminal application of potent and prolonged vasoconstrictors; or 4) the introduction of emboli into the cerebral circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457263 TI - Bioequivalence of inhaled medications. PMID- 1457264 TI - Determination of the relative bioavailability of salbutamol to the lung following inhalation. AB - 1. The urinary excretion of salbutamol and its sulphate metabolite was measured following oral (4 mg) and inhaled (4 x 100 micrograms) administration of salbutamol. 2. Total urinary recovery of salbutamol and its sulphate conjugate indicated a mean (s.d.) relative bioavailability of 92.2 (24.8) % following inhalation compared with oral administration. 3. The mean (s.d.) elimination half lives of salbutamol and its sulphate conjugate were 5.7 (1.4) and 4.1 (2.1) h, respectively, after oral administration and following inhalation they were 6.1 (2.1) and 5.1 (1.0) h, respectively. 4. Following oral and inhaled administration it was found that in the first 30 min the mean (s.d.) percentage of the dose excreted in the urine as unchanged salbutamol was 0.18 (0.14) and 2.06 (0.80) %, respectively (P < 0.01). The drug content of a urine sample taken 30 min after inhalation is, therefore, considered to be representative of the amount of drug delivered to the lungs. It is proposed that this method can be used to evaluate the relative bioavailability of salbutamol to the lung following inhalation by different techniques and devices. PMID- 1457265 TI - Ethanol kinetics: extent of error in back extrapolation procedures. AB - 1. Plasma ethanol concentrations were measured in 24 male volunteers for 9 h after a single oral dose of 710 mg kg-1. 2. The rate of decline of the plasma ethanol concentration (k0; mean +/- s.d.), was 186 +/- 26 mg l-1 h-1. 3. In each individual, three elimination rates were used to back-extrapolate plasma ethanol concentrations over 3 and 5 h periods from observed values at 4 h and 6 h post dosing assuming zero-order kinetics. The extrapolated values were then compared with the observed concentrations. 4. Using the mean k0 values for the subjects the mean error in back extrapolation was small but highly variable. The variability in the error increased with the length of the extrapolation period. 5. When a k0 value of 150 mg l-1 h-1 (a value often cited as a population mean) was used for back extrapolation this resulted in significant under-estimation of actual values whereas the use of a k0 value of 238 mg l-1 h-1 (the highest value observed in the present study) resulted in significant over-estimation of actual values. 6. These results indicate that because the kinetics of ethanol are associated with substantial inter-subject variability the use of a single slope value to back calculate blood concentrations can give rise to considerable error. PMID- 1457266 TI - Histamine N-methyl transferase: inhibition by drugs. AB - 1. Histamine N-methyl transferase activity was measured in samples of human liver, brain, kidney, lung and intestinal mucosa. The mean (+/- s.d.) rate (nmol min-1 mg-1 protein) of histamine N-methylation was 1.78 +/- 0.59 (liver, n = 60), 1.15 +/- 0.38 (renal cortex, n = 8), 0.79 +/- 0.14 (renal medulla, n = 8), 0.35 +/- 0.08 (lung, n = 20), 0.47 +/- 0.18 (human intestine, n = 30) and 0.29 +/- 0.14 (brain, n = 13). 2. Inhibition of histamine N-methyl transferase by 15 drugs was investigated in human liver. The IC50 for the various drugs ranged over three orders of magnitude; chloroquine was the most potent inhibitor. 3. The average IC50 values for chloroquine were 12.6, 22.0, 19.0, 21.6 microM in liver, renal cortex, brain and colon, respectively. These values are lower than the Michaelis Menten constant for histamine N-methyltransferase in liver (43.8 microM) and kidney (45.5 microM). Chloroquine carried a mixed non-competitive inhibition of hepatic histamine N-methyl transferase. Some side-effects of chloroquine may be explained by inhibition of histamine N-methyl transferase. PMID- 1457267 TI - The influence of posture on the pharmacokinetics of orally administered nifedipine. AB - 1. Nifedipine (20 mg as capsules) and soluble paracetamol (1 g) were co administered to eight healthy young volunteers on three separate occasions, following which in random order they stood, lay on their left side or lay on their right side for 4 h. 2. The time to maximum plasma concentration of paracetamol was significantly lower when standing or lying on the right side compared with recumbent left, indicating more rapid gastric emptying. 3. The times to maximum plasma concentrations of nifedipine and its metabolite produced at first pass were reduced when standing or lying on the right side. These postures were associated with significantly higher peak plasma concentrations and AUC values of nifedipine but not of its nitropyridine metabolite. 4. The increase in heart rate following nifedipine administration was significantly greater when lying on the right side compared with the left. 5. The data are consistent with transient saturation of first pass metabolism of nifedipine with postures which favour rapid gastric emptying. The results demonstrate the importance of defining the precise posture in studies in which pharmacokinetic and pharmacodynamic measurements are made on drugs which are absorbed rapidly and are subject to presystemic elimination. PMID- 1457268 TI - The effect of a prostaglandin DP-receptor partial agonist (192C86) on platelet aggregation and the cardiovascular system in healthy volunteers. AB - 1. PGD2 (DP)-receptors mediate inhibition of platelet aggregation and vasodilatation. If receptor reserve were greater on platelets it might be possible to separate these effects. To determine whether such a difference in receptor reserve exists, we have examined the effects of a highly selective DP receptor partial agonist 192C86 on platelet aggregation and the cardiovascular system in healthy volunteers. 2. Using an open, dose-escalating study design, four male volunteers received constant rate intravenous infusions of 192C86 for up to 60 min. Ex vivo platelet aggregation to ADP and collagen in platelet-rich plasma (PRP) and whole blood (WB) was studied at baseline, after 15, 30 and 60 min of each infusion and at 180 min post-infusion. Heart rate (HR), systolic and diastolic (DBP) blood pressure were measured at frequent intervals. Adverse experiences were monitored by checklist. Facial flushing was assessed by the volunteer using a visual analogue scale, by an observer using a numerical scale and by full-face colour photographs. Blood was taken for assay of plasma 192C86 concentrations by radio-immunoassay (r.i.a.). 3. 192C86 (0.007-0.058 micrograms kg-1 min-1) inhibited platelet aggregation to ADP and collagen both in PRP and WB in a dose-dependent manner. However, this was always accompanied by a decrease in DBP, increase in HR and facial flushing. Plasma concentrations of 192C86 were at or below the limits of sensitivity of the r.i.a. (0.5 ng ml-1). 4. The highest infusion rate was stopped after 20 min due to symptomatic hypotension on standing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457269 TI - Ginkgo biloba for cerebral insufficiency. AB - 1. By means of a critical review we tried to establish whether there is evidence from controlled trials in humans on the efficacy of Ginkgo biloba extracts in cerebral insufficiency. 2. The methodological quality of 40 trials on Ginkgo and cerebral insufficiency was assessed using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. A comparison of the quality was made with trials of co-dergocrine, which is registered for the same indication. 3. There were eight well performed trials out of a total of 40. Shortcomings were limited numbers of patients included, and incomplete description of randomization procedures, patient characteristics, effect measurement and data presentation. In no trial was double-blindness checked. Virtually all trials reported positive results, in most trials the dosage was 120 mg Ginkgo extract a day, given for at least 4-6 weeks. For the best trials, there were no marked differences in the quality of the evidence of the efficacy of Ginkgo in cerebral insufficiency compared with co-dergocrine. The results of the review may be complicated by a combination of publication bias and other biases, because there were no negative results reported in many trials of low methodological quality. 4. Positive results have been reported for Ginkgo biloba extracts in the treatment of cerebral insufficiency. The clinical evidence is similar to that of a registered product which is prescribed for the same indication. However, further studies should be conducted for a more detailed assessment of the efficacy. PMID- 1457270 TI - Perturbation of paracetamol urinary metabolic ratios by urine flow rate. AB - The effects of high and low urine flow rates on the urinary metabolic ratios for paracetamol glucuronidation, sulphation and oxidation were determined at steady state in seven healthy young adult volunteers. Metabolic partial clearances were unaffected by urine flow rate, but individual paracetamol metabolic ratios varied 2.5- to 3.2-fold over a 7.4-fold range of urine flow rates (0.81-6.00 ml min-1). The change in metabolic ratios was due entirely to a 2.5-fold change in renal clearance of unchanged paracetamol. These data emphasise the limitations of the metabolic ratio as a measure of intrinsic clearance for compounds which undergo some degree of tubular reabsorption. PMID- 1457271 TI - Effect of angiotensin converting enzyme inhibitors on erythropoietin concentrations in healthy volunteers. AB - The possibility that the ACE inhibitors, enalapril and captopril, may decrease plasma EPO concentrations was studied in a single-blind, cross-over study in 10 healthy volunteers. Plasma EPO concentrations, haemoglobin concentration, red blood cell count, plasma creatinine concentration and mean arterial pressure were measured at baseline and after 28 days treatment with both ACE inhibitors. A significant fall in mean plasma EPO concentration occurred with both ACE inhibitors and returned to baseline after stopping the drugs. It is likely that ACE inhibitors decrease EPO formation, by inhibition of angiotensin-II production. This effect could be important in patients with renal failure, renal transplantation or other chronic conditions with an associated anaemia. Haematological parameters should be monitored in such patients when they are treated with an ACE inhibitor. PMID- 1457272 TI - Effect of alacepril on blood pressure and neurohumoral factors at rest and during dynamic exercise in patients with essential hypertension. AB - We assessed blood pressure and neurohumoral factors at rest and during exercise in 10 patients with essential hypertension before and after treatment with the new angiotensin converting enzyme inhibitor, alacepril (25-50 mg day-1). Alacepril significantly lowered mean blood pressure at rest and at the same exercise load as before treatment without affecting heart rate response. The response of plasma renin activity, plasma aldosterone, and plasma adrenaline were not changed by alacepril, but increase of plasma angiotensin II and plasma noradrenaline during exercise were significantly attenuated after alacepril treatment (ANOVA, P = 0.04, both). The change in mean blood pressure during exercise was positively correlated with the decrease in plasma angiotensin II (r = 0.65, P < 0.05). These results demonstrated that alacepril was effective in essential hypertension both at rest and during exercise, suggesting that the antihypertensive effect during exercise might be related to the decrease in pressor hormones, especially in plasma angiotensin II. PMID- 1457273 TI - Duchenne muscular dystrophy. AB - Advances in the understanding of the genetic basis for Duchenne muscular dystrophy over the past 4 years has led to the quick application of molecular diagnostics. More recently, attention has turned towards acquiring a better understanding of dystrophin biochemistry and the pathophysiologic consequences of dystrophin deficiency. PMID- 1457274 TI - Muscle fiber types and function. AB - A major recent advance in the field of muscle fiber types has been the discovery that myogenic factors regulate fiber phenotypic properties. Myogenic influences occur in limb and trunk (somitic) muscle, but are particularly strong in jaw closing muscles and extraocular muscles that express some unique myofibrillar proteins. In somitic muscles, a variant of fast fiber has been discovered, making four types of fibers: I, IIA, IIX, and IIB. These fibers express different isoforms of myofibrillar and other proteins. The speed and power of the four types of fibers are distinct and are controlled principally by their myosin heavy chains, which modulate the two regulatory steps in the crossbridge cycle, one controlling the rate of development of force, the other controlling the maximal velocity of shortening. Fast fibers have a higher threshold for Ca(2+)-activated force and a steeper force-pCa relation than do slow fibers. This difference is largely attributable to the cooperativity in the attachment of crossbridges and to the difference in Ca2+ binding capacity of their troponin C. Ca2+ initiates force development in muscle by increasing the rate of attachment of crossbridges. The phosphorylation of myosin light chain enhances this action. This effect of phosphorylation underlies the phenomenon of posttetanic potentiation of the isometric twitch in fast fibers. PMID- 1457275 TI - Clinical applications of muscle enzymes and proteins. AB - Total creatine kinase measurement in serum has remained the best overall marker for detection and monitoring of skeletal muscle diseases, despite that different human tissues exhibit varying distributions of cytoplasmic and mitochondrial isoenzymes of creatine kinase. Acute myocardial infarction aside, increases in total serum creatine kinase, as reflected by the MM isoenzyme, are most commonly caused by injury or diseases to striated muscle. Enzyme markers of skeletal muscle injury that have been previously used (eg, aldolase, enolase, aspartate aminotransferase, and lactate dehydrogenase isoenzyme 5) are not as specific as creatine kinase and have limited clinical utility. However, new enzyme and protein markers are currently being investigated, eg, troponin and carbonic anhydrase III, which are more specific than creatine kinase toward particular tissues. Moreover, measurement of creatine kinase isoforms may provide information about whether muscle turnover is acute or chronic. PMID- 1457276 TI - Raynaud's phenomenon, scleroderma, overlap syndromes, and other fibrosing syndromes. PMID- 1457277 TI - Raynaud's phenomenon. AB - Raynaud's phenomenon occurs in about 5% of the adult population, and most individuals do not seek medical attention for the condition. In symptomatic patients with Raynaud's phenomenon, it is useful to categorize the condition as primary or secondary. In addition to providing a framework for epidemiologic and therapeutic protocols, such classification may reflect basic pathophysiologic differences. Occupation-related Raynaud's phenomenon has been recognized recently as a major cause of lost wages and productivity. Neurogenic and "local fault" hypotheses to explain primary Raynaud's phenomenon are still being studied. In secondary Raynaud's phenomenon, obliterative arteriopathy and the role of endothelial-derived products have been the focus of intense research interest. Under some circumstances, the combination of nailfold capillary microscopy and autoantibody analysis can identify patients with primary Raynaud's phenomenon that is likely to evolve into a secondary form of Raynaud's phenomenon. Although information from this type of analysis may be overinterpreted, the prognostic yield is highest for patients destined to develop systemic sclerosis-related disorders. Newer vasodilating agents and antithrombotic drugs may offer benefit for patients with both primary and secondary Raynaud's phenomenon. PMID- 1457278 TI - Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions. AB - Many patients presenting with symptoms suggestive of a connective tissue disease do not fulfill criteria for a specific connective tissue disease at initial presentation. Some of these patients with undifferentiated connective tissue disease eventually develop a specific connective tissue disease. Recently, a large cohort of 213 patients from different centers with undifferentiated connective tissue disease of early onset were enrolled in a prospective protocoled study. Baseline characteristics, including antinuclear antibody profiles, were reported. The aim of this study was to define predictors for the development of specific organ-system involvement and connective tissue diseases in early undifferentiated connective tissue disease. Many patients show overlapping features of two or more connective tissue diseases. The presence of autoantibodies to U1-ribonucleoproteins has been associated with a particular overlap syndrome, mixed connective tissue disease. Most anti-U1-ribonucleoprotein positive patients with undifferentiated connective tissue disease at presentation appear to develop mixed connective tissue disease over the course of disease. Although levels of anti-U1-ribonucleoprotein do not seem to be related to disease activity, this association suggests a pathogenetic relationship between anti-U1 ribonucleoprotein and mixed connective tissue disease. Genetic studies have shown that patients with antibodies against the 70-kD component of U1-ribonucleoprotein share a common epitope within the groove of their DR molecules at antigen-binding region, pointing to a particular antigen involved in the induction of these antibodies that may be relevant in the etiopathogenesis of associated disease. PMID- 1457279 TI - Clinical aspects of localized and systemic sclerosis. AB - Now that renal disease is no longer the leading cause of death in patients with systemic sclerosis, attention has shifted to cardiopulmonary involvement. Several reports addressed the issue of whether the pulmonary vasculature in patients with systemic sclerosis is vasoactive or fixed, and one report addressed the use of high-resolution computed tomographic lung scan to diagnose active alveolitis. The issue of whether the clinical syndrome of thrombotic thrombocytopenic purpura in systemic sclerosis is part of, or is distinct from, scleroderma renal crisis has again been raised. Worsening of cutaneous and visceral systemic sclerosis following radiotherapy was noted in several reports. PMID- 1457280 TI - Eosinophilia-myalgia syndrome, toxic-oil syndrome, and diffuse fasciitis with eosinophilia. AB - The eosinophilia-myalgia syndrome, which is associated with the ingestion of L tryptophan that contained products, occurred as an epidemic in the United States in 1989. Eosinophilia-myalgia syndrome is similar in many ways to the toxic-oil syndrome, which occurred in Spain in 1981, and to diffuse fasciitis with eosinophilia, which has been noted since 1974 to occur sporadically. Recent studies have clarified the epidemiology, histopathology, and clinical features of eosinophilia-myalgia syndrome. These studies are reviewed, and comparisons to the related syndromes, toxic-oil syndrome and diffuse fasciitis with eosinophilia, are made. PMID- 1457281 TI - Genetic and environmental factors in systemic sclerosis. AB - The occurrence of autoantibodies in patients with systemic sclerosis has suggested a role for immune dysregulation in this disease. Recent genetic studies have concentrated on the major histocompatibility complex-encoded antigens and found an association of particular HLA-DQ alleles with anticentromere antibodies. Although the role of major histocompatibility complex antigens and autoantibodies in the pathogenesis of systemic sclerosis remains unclear, determination of major histocompatibility complex alleles may have clinical value in identifying patients who are at increased risk for development of pulmonary fibrosis or rapidly advancing skin disease. A variety of environmental factors have been associated with systemic sclerosis-like skin diseases, including silica, vinyl chloride, paraffin, adulterated L-tryptophan, and "toxic" rapeseed oil. It has been suggested that silicone used during breast augmentation may be a risk factor for development of systemic sclerosis, but ascertainment bias in case reporting makes interpretation of these studies difficult. The heterogeneity of clinical features, major histocompatibility complex status, and autoantibody profiles in systemic sclerosis suggest that this disorder may actually be a group of distinct disorders, each of which has its own characteristic genetic and environmental predisposing risk factors. PMID- 1457282 TI - Immunologic aspects of scleroderma. AB - Recent investigations of immunologic events in systemic sclerosis focus on the identification of which immune system cells are participating in the disease process, what antigens are stimulating the T and B cells, which cytokines are involved, and which cell adhesion molecules promote cell-cell and cell extracellular matrix interactions. Increased numbers of gamma/delta and activated CD4+ T cells are present in involved skin of line-200 chickens, an animal model of systemic sclerosis. CD4+ T cells from patients with systemic sclerosis are stimulated by human type I collagen, and immunoglobulins from some patients with systemic sclerosis bind retroviral proteins, the terminal galactosyl (alpha 1-3) galactose disaccharide of laminin, or a 138 amino acid region of the PM-Scl antigen. The development of an anticentromere antibody response in patients with systemic sclerosis appears to require the presence of a polar amino acid at position 26 in the antigen-binding cleft of the HLA-DQB1 molecule. Interleukin-2, interleukin-4, interleukin-6, and transforming growth factor-beta have been implicated as cytokines that may be involved in the pathogenesis of systemic sclerosis. Increased expression of intercellular adhesion molecule 1 (ICAM-1) on systemic sclerosis fibroblasts is responsible for increased binding of T cells to those fibroblasts through ICAM-1/lymphocyte function-associated antigen 1 interactions. beta 1 and beta 2 integrins, ICAM-1, and endothelial leukocyte adhesion molecule 1 all may be involved in the homing of lymphocytes to involved skin in patients with systemic sclerosis. PMID- 1457283 TI - Connective tissue metabolism including cytokines in scleroderma. AB - Scleroderma fibrotic lesions demonstrate vascular disease, mononuclear cell infiltrates, and increased collagen. Fibroblasts in these lesions are activated to synthesize increased extracellular matrix substances, a phenotype that continues when these cells are removed and grown in tissue culture. Levels of messenger RNA for connective-tissue substances, measured directly in biopsies of scleroderma skin, show increased message for type I collagen, but not type III collagen or fibronectin. Increased procollagen type I in scleroderma skin occurs in the papillary dermis, perivascular areas, and deep interstitium, even in skin areas that are not yet fibrotic. Scleroderma fibroblasts express more intercellular adhesion molecule 1 on their surfaces than do normal cells, and this molecule is increased in endothelial cells, mononuclear cells, and fibroblasts. In vitro scleroderma fibroblasts adhere more frequently to extracellular matrix substances and retract collagen lattices to a greater extent. Peripheral blood lymphocytes from scleroderma patients produce excessive amounts of interleukin-2 when incubated with type I collagen, and circulating basophils release more histamine than do normal cells. There is evidence for activated eosinophils both in the dermis and pulmonary lesions in scleroderma, which may play a role in fibrosis. Transforming growth factor-beta is overexpressed by alveolar macrophages from patients with fibrotic pulmonary disease. Scleroderma fibroblasts, when exposed to transforming growth factor beta, overexpress the alpha-type receptor for platelet-derived growth factor. Scleroderma sera more frequently contain measurable quantities of interleukin-4, interleukin-6, and interleukin-2. Interleukin-4 causes adult dermal fibroblasts to proliferate and to make interleukin-6. Interleukin-6 has been shown to stimulate fibroblast synthesis of collagen and glycosaminoglycans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457285 TI - Myositis and myopathies. PMID- 1457284 TI - Treatment of systemic sclerosis. AB - A new awareness of the challenges and pitfalls of clinical research in patients with systemic sclerosis has recently arisen. Several editorials discussed concern about the design of therapeutic trials and the need to use established scientific standards to find better markers of disease activity and better ways to measure improvement or deterioration of organ involvement, including the heart, lung, and gastrointestinal tract. This year, an uncontrolled experience in the use of D penicillamine in the treatment of patients with rapidly progressive skin involvement was reported. In addition, a multicenter study of photopheresis demonstrated benefit compared with D-penicillamine. Several new prokinetic drugs demonstrated promise for the treatment of gastrointestinal disease in patients with systemic sclerosis. Although studies continue to demonstrate the benefit of intravenous prostaglandins in the treatment of Raynaud's phenomenon and digital ulcers in scleroderma, an initial report of oral prostaglandins was disappointing. Clinical researchers are now working together to design multicenter studies and to define new uniform standards of disease activity so that the appropriate treatment for systemic sclerosis can be determined. PMID- 1457286 TI - Raynaud's phenomenon, scleroderma, overlap syndromes, and other fibrosing syndromes. PMID- 1457287 TI - The effect of pH on the thermal resistance of Clostridium sporogenes (PA 3679) in asparagus puree acidified with citric acid and glucono-delta-lactone. AB - The influence of type of acid, pH and temperature on heat resistance of Clostridium sporogenes (PA 3679) spores were investigated in white asparagus puree acidified with citric acid and glucono-delta-lactone (GDL). The pH values studied were: 4.5, 4.8, 5.1 and 5.4 at temperatures of 110, 115, 118 and 121 degrees C. The addition of citric acid and GDL to reduce pH significantly diminished heat resistance of the spores. The two acids investigated differed in their effect on heat resistance at the various pH-levels. The most pronounced effect was observed at the lower heat treatment temperatures investigated. The z values ranged from 10.24 to 13.09 degrees C in the asparagus puree with acids added and with significant differences between the two acids and the various pH levels. PMID- 1457288 TI - Bacteriocin (monocin) interactions among Listeria monocytogenes strains. AB - Monocin interactions of 97 strains of Listeria monocytogenes were assessed using an improved production method and standardisation of the monocins against the type strain of L. ivanovii. Monocins were resistant to trypsin, sensitive to heating at 56 degrees C for 30 min and stable at 4 degrees C. Only serovar 4 strains acted as indicators. A typing system using 8 producer and 11 indicator strains showed poor discrimination. PMID- 1457289 TI - Salmonella and Vibrio cholerae in brackishwater cultured tropical prawns. AB - The occurrence of Salmonella and Vibrio cholerae in brackishwater ponds was monitored over a 2-year period in one of the major prawn exporting countries in Southeast Asia. The principal production areas were identified and regular samples taken for Salmonella and V. cholerae analysis. Results demonstrated that brackishwater ponds and cultured prawns were inherently contaminated with both bacterial pathogens. Salmonella spp. were present in 16.0% of prawns and 22.1% of mud/water samples from ponds; and V. cholerae present in 1.5% of prawns and 3.1% of mud/water samples. Culturing by intensive methods tended to favour contamination by these pathogens, which is most likely due to the accumulation of waste and increase in the volume of sediments in ponds. Typical environmental factors such as water temperature, pH, and salinity were all favourable for growth of microorganisms. The incidence of the pathogens increased during the wet season and was marginally higher when ponds were located close to urban areas. S. weltevreden was identified as the principal serotype found in ponds, and to a lesser extent S. anatum (11%) S. wandsworth (8%) and S. potsdam (8%). The V. cholerae belonged to the non-O1 serogroup. PMID- 1457290 TI - Accelerated natural lactic fermentation of cereal-based formulas at reduced water activity. AB - Energy required to dehydrate fermented cereal-based food formulas plays a significant part in the production cost. Therefore the effect of reduced moisture content on the fermentation was investigated. Generally, lactic fermentation at reduced moisture content resulted in increased final pH. Significant acidification still occurred at 0.33 kg water/kg dry matter corresponding to either aW = 0.925 in a sorghum-maize-soya (SMS) mixture, or aW = 0.950 in a sorghum-maize-milk powder (SMM) mixture. Acidification adequate for microbiological safety (pH < or = 4.5) was achieved at 0.54 kg water/kg dm in SMS (aW = 0.950) and 0.43 kg/kg dm in SMM (aW = 0.965). In stable accelerated natural lactic fermentations obtained by inoculum recycling ('back-slopping') at 30 degrees C, dominant lactic acid bacteria included Lactobacillus plantarum, L. brevis, L. acidophilus and Lactococcus lactis. Dominating yeasts were Saccharomyces cerevisiae and Candida krusei. L. plantarum isolated from high moisture (1.5 kg/kg dry matter) SMS fermentations had higher specific growth rates than L. plantarum isolated from reduced moisture (0.54 kg/kg dm) SMS fermentations, when tested under similar aW conditions. This effect was not caused by previous culturing conditions; probably different strains of L. plantarum having different aW-optima dominate at high or reduced moisture conditions. PMID- 1457291 TI - Minimal water activity levels for growth and survival of Listeria monocytogenes and Listeria innocua. AB - Following initial range-finding experiments, total count determinations were used to determine minimal water activity (aW) levels for the growth and survival of Listeria monocytogenes (L.m.) and L. innocua (L.i.). Media containing three different humectants; NaCl, sucrose or glycerol were used to determine minimal aW levels for growth in the above media which were 0.92, 0.92 and 0.90 respectively. The growth minima for L.i. were similar, or slightly higher than for L.m. in these media. Survival rates were generally lower in NaCl-adjusted media than in systems adjusted with sucrose or glycerol. Survival of L.m. and L.i. in these experiments was similar. PMID- 1457292 TI - Antibacterial activity of essential oil components. AB - Antibacterial activity of fifteen essential oil components towards food borne Staphylococcus sp., Micrococcus sp., Bacillus sp. and Enterobacter sp. was studied by an agar plate technique. Cinnamic aldehyde was the most active compound followed by citral, geraniol, eugenol and menthol. At 500 micrograms/ml, cinnamic aldehyde completely inhibited the bacterial growth for more than 30 days at 30 degrees C that was comparable to 200 micrograms/ml of butylated hydroxy anisole (BHA). At lower temperatures, 25 and 20 degrees C, antibacterial activity of the five essential oil components increased. Addition of sodium chloride at 4% level (w/v) in the medium had no effect on the inhibitory activity of cinnamic aldehyde. In mixtures of cinnamic aldehyde and eugenol or BHA an additive effect was observed. PMID- 1457293 TI - Preliminary examinations on the enterotoxigenicity of isolates of Klebsiella pneumoniae from seafoods. AB - One hundred and eighty-five seafood samples, consisting of 96 freshwater fish, 37 marine fish, 13 freshwater prawn, 13 marine prawn and 26 molluscs were screened for presence of Klebsiella. Out of these, 12 isolates of Klebsiella were identified, Four K. pneumoniae var. ozaenae were isolated from marine fish samples and eight K. pneumoniae var. pneumoniae, six from freshwater fish and two from freshwater prawns. All 12 isolates were tested for enterotoxigenicity by the vasopermeability factor test in rabbits, the mouse foot pad test, the latex agglutination test and the coagglutination test. One isolate of K. pneumoniae var pneumoniae, isolated from fresh water prawn was found enterotoxigenic. PMID- 1457294 TI - Rectal administration of perforated nifedipine capsules in acute severe hypertension in children. AB - Nine hypertensive children (mean age: 5.0 years (SD: 4.5), range: 10 months to 15 years) were administered nifedipine (capsule) rectally (0.2 to 0.5 mg/kg) when their blood pressures were over 170 mmHg systolic and/or over 110 mmhg diastolic, independent of their ages. The causes of hypertension were acute glomerulonephritis (n = 2), chronic glomerulonephritis (n = 2), renovascular hypertension (n = 4), and polycystic kidney (n = 1). Both systolic and diastolic blood pressures fell in all children after rectal administration of nifedipine, although the response of blood pressure was weak in one child with renovascular hypertension. Blood pressures were lowest at 30 to 60 minutes, and remained under 140 mmHg systolic and 80 mmHg diastolic at least for three hours. Side-effects were headache in one child, palpitations in two children, and facial flushing in three. All of these symptoms were mild, and no special treatment was required. These findings suggest that rectal administration of nifedipine may be effective and the most reliable way to treat young children with severe or urgent hypertension. PMID- 1457295 TI - Hypothalamo-pituitary-adrenal axis suppression in asthmatic adults taking high dose beclomethasone dipropionate. AB - Inhaled corticosteroids control symptoms of chronic asthma in most patients. Use of drugs such as beclomethasone dipropionate (BDP) and budesonide is being encouraged as the importance of airways inflammation in asthma is increasingly appreciated. Beclomethasone dipropionate is used in doses of up to 2000 micrograms daily (equivalent to eight puffs of Beclorforte inhaler) and the Data Sheet warns that systemic absorption sufficient to cause suppression of the hypothalamo-pituitary-adrenal (HPA) axis may occur in some patients taking 2000 micrograms. HPA suppression to an extent which is clinically relevant has not been reported in asthmatic adults taking lower doses of BDP. We report six cases of HPA hypofunction occurring in patients on long-term treatment with BDP, in a dose of 1500 micrograms daily. Patients taking BDP in a dose of 1500 micrograms daily might be at risk of adrenal crisis and should carry steroid cards unless HPA function has been assessed and found normal. PMID- 1457296 TI - Home sweet HEN--a guide to home enteral nutrition. AB - Initial experience of home enteral nutrition (HEN) was gained from malnourished patients with Crohn's disease. The rationale for HEN was to improve the patients' lifestyle by reducing the need for repeated admissions for nutritional support: this method is extremely useful in correcting nutritional problems. Over the past ten years the use of HEN has expanded to cover other clinical areas including correction of growth retardation secondary to gastrointestinal disease, cystic fibrosis, inborn errors of metabolism, congenital heart disease, and chronic renal failure, in addition to many types of neoplasia and chronic neurological diseases. At the present time, approximately 150 patients receive HEN within the catchment area of the Greater Glasgow Health Board (population 940,000). Despite the increasing availability of HEN many clinicians and dietitians are still reluctant to consider HEN as a 'routine adjunct' to clinical management, claiming that it is too dangerous or complicated. The aims of this article are to explain our method of running a HEN service, offer advice on practical problems and discuss further developments and potential difficulties. PMID- 1457297 TI - The role of echocardiography in the diagnosis and management of infective endocarditis. AB - The echocardiographic appearance in suspected endocarditis must always be interpreted in the context of the clinical findings. Thus although echocardiography may contribute to the early diagnosis of infective endocarditis, it should rarely be used as a screening test. It is highly sensitive for the detection of complications such as abscesses or valvular regurgitation and can estimate their severity. Although transthoracic imaging will allow a complete study in many cases, the transoesophageal approach is superior for the detection of abscesses and the assessment of prosthetic mitral valves. Patients with large vegetations, particularly on the mitral valve, are at increased risk of embolism but there is no convincing evidence to support prophylactic surgery in these cases. PMID- 1457298 TI - Exercise in post infarct rehabilitation. AB - In 1957, Hellerstein and Ford defined rehabilitation as 'the process by which a patient is returned realistically to his greatest physical, mental, social, vocational and economic usefulness and, if employable, is provided an opportunity for gainful employment in a competitive industrial world'. They stressed the importance of starting the rehabilitation process 'at the moment the patient is first stricken with his disease', of mobilising the patient as soon as is practical and of paying close attention to the emotional as well as physical consequences of the attack. They believed that 80% of the aftercare of cardiac patients could be managed by the 'private physician' and only a minority required the attention of a specialist team. The time scale used in 1957 (three to four weeks in hospital) was rather different to the one we use today, but otherwise most of what he suggested then has scarcely been improved upon since. In 1968 Hellerstein went on to describe the physical training programme he had devised to improve the fitness of 'habitually lazy, hypokinetic, sloppy, endomesomorphic over-weight males' who were the usual victims of myocardial infarction. He wished to 'add life to years and perhaps add years to life'. The conclusions from his original study were that 'an active intervention programme of conditioning including exercise, weight reduction, diet therapy, and cessation of smoking is feasible, reasonably acceptable and appears to be of benefit in the treatment of coronary heart disease'. PMID- 1457299 TI - Can selection of medical staff be improved? AB - Selection procedures for medical staff have been reviewed. Much can be learnt from industrial practices, including the adoption of 'person specifications', improved references, structured interviews and training for interviewers. Possible supplementation with personality assessments is discussed. The clinical (and financial) importance of appointing the best candidate increased with the seniority of the post. PMID- 1457300 TI - Aortic dissection. AB - Aortic dissection, once thought to be rare, is the most common catastrophe of the aorta, being twice as common as ruptured abdominal aortic aneurysm. In one Inner London borough, aortic dissection accounted for 4.2% of sudden deaths in men over a three-year period. Early diagnosis and prompt treatment are crucial to achieving a successful outcome, because the events that influence survival occur early in the course of the disease. Surgical repair of aortic dissection is an uncommon operation in the United Kingdom. The Cardiac Surgical Register for 1988 (the most recent year available for analysis) reveals that 208 operations were performed to replace the ascending aorta, 12 operations to replace the aortic arch and 15 operations on the descending aorta during that year. PMID- 1457302 TI - Primary hyperparathyroidism and renal cell carcinoma in an elderly patient: a rare association. AB - A case of an elderly female patient, presented with a rare association of primary hyperparathyroidism and renal cell carcinoma, is reported. As a common finding in the elderly, the patient had mild hypercalcaemia for many years but she developed several complications from untreated hyperparathyroidism. The mechanisms of malignant hypercalcaemia are discussed and the importance of properly investigating and managing symptomatic primary hyperparathyroidism in the elderly is emphasised. PMID- 1457301 TI - Assessment of reversibility in patients with chronic airflow obstruction. AB - Reversibility of airflow obstruction was considered for many years to be a hallmark of asthma. It is now clear that many patients with chronic airflow obstruction, often labelled as chronic obstructive airways disease or chronic bronchitis and emphysema, show some bronchodilation following various drugs. At present there is no clinical or physiological factor which reliably predicts the bronchodilator response of such patients to a given medication, and individual testing of these drugs is necessary. However, the literature on bronchodilator responses in chronic airflow obstruction is confused. There are differences in the selection of patients, the tests used and the interpretation of the results. The aim of this review is to highlight the main problems found when measuring reversibility in such patients, the different factors that influence the reversibility testing and the biases which may confound the interpretation of the results. PMID- 1457303 TI - Quinine-induced cutaneous vasculitis. AB - We report a 60-year-old woman who developed severe cutaneous vasculitis three weeks after commencing quinine sulphate (300 mg at night) for nocturnal cramps. The patient died despite immunosuppressive treatment with prednisolone and cyclophosphamide. We review three previous cases and conclude that cutaneous vasculitis is a rare but life-threatening complication of treatment with this widely-prescribed drug. Quinine sulphate is prescribed frequently for nocturnal cramps, although its efficacy is unsupported by stringently controlled clinical trials. Adverse reactions to the drug are unusual. We describe a 60-year-old woman with fatal cutaneous vasculitis related to quinine treatment. PMID- 1457304 TI - Hallucinations as a presenting feature in malignant hypertension. AB - A 68-year-old man with malignant hypertension of renovascular origin presented with visual impairment and complex visual hallucinations. Four weeks after the hypertension had been controlled by drugs, the hallucinations ceased and electroencephalographic evidence of encephalopathy resolved. PMID- 1457305 TI - Perforation of an abdominal viscus associated with a pneumothorax. AB - Pneumothorax is a very unusual presenting complication of a perforated abdominal viscus. We present two such cases. The importance of close scrutiny of chest radiographs taken for abdominal disease is stressed. PMID- 1457306 TI - A presentation of anaplastic carcinoma of the thyroid with symptomatic intra abdominal metastases. AB - Anaplastic thyroid carcinoma usually presents with symptoms related to local invasion and compression of structures in the neck. We report a patient with intra-abdominal metastases presenting with symptoms suggestive of local gastrointestinal disease. Abdominal CT scan and initial laparotomy findings were suggestive of an abdominal aortic aneurysm. PMID- 1457307 TI - Alveolar rhabdomyosarcoma: a case presentation. AB - We present a case report of an unusual tumour, presenting as a mass on the forearm. We have used this case to review the current literature and histological classification of rhabdomyosarcoma. PMID- 1457308 TI - Idiopathic retroperitoneal haematoma. AB - A case of asymptomatic idiopathic retroperitoneal haematoma presenting as an abdominal tumour, is described. A review of English literature has not revealed any description of this condition. PMID- 1457309 TI - Apparent elevation of serum CK-MB not due to acute myocardial infarction. AB - An increased serum level of the MB isoenzyme of creatine kinase (CK-MB) is a useful marker for acute myocardial infarction. Although described extensively in clinical chemistry literature, there is little information in standard medical references about false positives for this test. We report two cases where high levels of measured CK-MB activity were in fact due to another form of CK, associated with internal malignancy. PMID- 1457310 TI - Long-term survival of a patient with malignant lymphoma of bone. AB - Malignant lymphoma of bone is an uncommon tumour. A number of studies have outlined the clinicopathological findings and overall favourable prognosis in adults. We report on a woman whose tumour was originally diagnosed as a secondary carcinoma of the upper femur. Twenty-three years later following proximal femoral replacement, the original histology was reviewed using immunohistochemical techniques and revised to B-cell malignant lymphoma of bone. PMID- 1457311 TI - '3-in-1' nerve block complicated by haemospermia. PMID- 1457312 TI - Tamoxifen and hypercalcaemia. PMID- 1457313 TI - Cardiac rehabilitation: an essential service. PMID- 1457314 TI - Sleep disorders in clinical practice. PMID- 1457315 TI - Blood is thicker than water: haemorheology in clinical practice. PMID- 1457316 TI - Quality of sleep in the medical department. AB - The quality of sleep in 134 patients admitted to two medical departments and an intensive coronary care unit was studied by comparing pre- and post-admission sleeping scores. Four aspects of sleep have been evaluated: duration of sleep; number of awakenings; personal assessment of quality of sleep; and the need for using sleeping pills. Results were expressed in scores ranging from 1 (worst) to 4 (best). A significant reduction in the mean quality of sleep for the entire group was found for all scores employed (P < 0.01-P < 0.001). Of the 134 patients, 51% had a reduction in post-admission total sleep score (23 +/- 3%, mean +/- SE); 31% had no change or mixed trends in the various scores, with a change in total sleep score not exceeding 3 +/- 3%; and 18% had an improved total sleep score (16 +/- 2%). Of the individual scores, a deterioration was found in the following order of frequency: number of awakenings (37%); personal assessment of quality of sleep (32%); duration of sleep (31%); and the need for using sleeping pills (26%). Of the reasons specified for impaired quality of sleep, the most important were noise made by other patients or by the medical staff (47%), and the patient's own disease (30%). Significant differences in the quality of sleep between the two medical departments located in different hospitals have been encountered (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457317 TI - Are non-steroidal anti-inflammatory drugs always necessary? A general practice survey. AB - The number of patients receiving long-term 'repeat prescriptions' for non steroidal anti-inflammatory drugs (NSAIDs) was examined in a General Practice; a group of them with osteoarthritis or musculoskeletal pain attempted to withdraw their NSAID treatment and substitute alternative analgesics. Thirty-eight randomly selected patients, with conditions other than rheumatoid arthritis, were interviewed and alternative analgesics prescribed to replace their NSAID therapy. After one month, 22 had very satisfactory pain relief without their NSAID but 16 had resumed therapy, with four of them on a reduced dosage; three others wished to try an alternative analgesic again. Five initially with gastro-intestinal symptoms were asymptomatic within a month of discontinuing their NSAID. After four months, 24 of the 38 had discontinued NSAIDs, including one who had an upper gastrointestinal haemorrhage during the study; two others were taking a reduced dosage. PMID- 1457318 TI - Dyspepsia in the community: a follow-up study. AB - We have repeated a population-based survey of the pattern and prevalence of dyspeptic symptoms in 2460 subjects two years after the original survey, in order to document the changes in dyspeptic symptoms and consultation behaviour. A validated postal questionnaire was sent to 2460 subjects randomly selected in ten year age bands from the lists of eight general practitioners working in the south of England. A total of 1417 individuals (58%) responded to both questionnaires. The overall six month prevalence of dyspepsia was unchanged (38%), but while 74% of dyspeptic patients were still getting symptoms, 13% became symptom-free each year. Over half of those who had reported dyspepsia before, but not at the time of, the first survey had experienced recurrence of their symptoms. In the two year study period 113 individuals experienced dyspepsia for the first time, giving an annual incidence of 11.5%. One in four patients consulted their general practitioner, and 75% of those who had not consulted in the first survey still had not done so two years later. Resolution of symptoms appeared independent of consulting behaviour. Peptic ulcers were identified in 14 patients, mostly those with new dyspepsia, during the study period. PMID- 1457319 TI - Humeral fractures in 'arm wrestlers'. AB - We report three cases of fractures of the shaft of the humerus occurring during arm wrestling contests, which have now become a common pub--and even professional -sport. We then review all the literature on the subject. This is an unusual injury occurring in arm wrestling, but does occur and it should be remembered that radiological assessment is vital if this injury is not to be missed and the injury mismanaged. PMID- 1457320 TI - Glomerular abnormalities in children undergoing orthotopic liver transplantation. AB - A prospective study of renal function was undertaken on an unselected group of 8 children with chronic progressive liver disease on whom a renal biopsy was performed subsequently at the time of orthotopic liver transplantation. Two patients had abnormal urinalyses and 2 elevated urinary albumin/creatinine ratios. The remainder had no clinical evidence of renal dysfunction. All had normal serum creatinine concentrations. Glomerular abnormalities were present in all renal biopsies and were of two types: hepatic glomerulosclerosis (n = 5) and minor glomerular abnormalities (n = 3). IgM immunofluorescence was present in all biopsies and IgA in 6. Elevated serum immunoglobulin levels were observed in all patients, with IgM elevation in 6, IgA in 4 and IgG in 6. C3 and/or C4 were reduced in 5 patients and increased circulating immune complexes containing IgM were noted in 4. The clinical significance of these cirrhosis-associated glomerular abnormalities can only be established by long-term follow-up studies after orthotopic liver transplantation. PMID- 1457321 TI - Prognosis of patients with unilateral renal agenesis. AB - The clinical course was reviewed in 157 patients with unilateral renal agenesis and a normal contralateral kidney for the purpose of establishing a prognosis. There were 85 males (54%) and 72 females (46%). The mean age at diagnosis of unilateral renal agenesis was 37 years. The mean years at risk was 56. Proteinuria (> 150 mg/24 h) was found in 19% of the 37 patients tested (P < 0.001), hypertension developed in 47% of the 47 patients tested (P = 0.010), and renal function (adjusted for age and sex) was decreased in 13% of the 32 patients tested (P = 0.001). An increased filtration fraction was found in 7 (54%) of 13 patients evaluated. At the completion of this study, 114 patients (73%) were alive, and the survival rate was similar to that of age-, sex-matched United States life tables. Forty-three patients (27%) died; 6 deaths (4%) were caused by renal failure. Our review indicates that patients with unilateral renal agenesis and a normal solitary kidney are at increased risk of proteinuria, hypertension, and renal insufficiency. Therefore, it is essential to have prolonged and careful follow-up and to employ strategies that maximize renal preservation. PMID- 1457323 TI - What makes red cells dysmorphic in glomerular haematuria? AB - Although red cell morphology has been used to localise the site of haematuria in the urinary tract, the cause of red cell deformity is still speculative. We have conducted experiments in vitro using venous red cells which indicate that hypochromia depends mainly upon sodium concentration and occurs when this falls below 75 mmol/l. We simulated the passage of red cells through the renal tubule by sequentially treating them with fluids of composition similar to those in different tubular segments, and produced anisocytosis and hypochromia but not the typical "bizarre deformity"--the hallmark of glomerular haematuria. We conclude that dual injury is required to produce the "typical" dysmorphic red cells in glomerular haematuria. First, mechanical damage caused by passage of red blood cells through the glomerular basement membrane followed by a second, osmotic, injury sustained by red cells during passage through the hypotonic tubular segment. PMID- 1457322 TI - Association of Kawasaki disease and interstitial nephritis. AB - Renal insufficiency is a rare manifestation of Kawasaki disease. We report a 2.5 year-old boy with Kawasaki disease who developed acute renal failure during the acute phase of his illness. A percutaneous renal biopsy revealed acute interstitial nephritis. No etiological agent could be identified and renal recovery occurred with supportive care alone. PMID- 1457324 TI - Renal hypoplasia and postnatally acquired cortical loss in children with vesicoureteral reflux. AB - We reviewed histologically 86 nephrectomy specimens from patients with vesicoureteral reflux (with or without ureterovesical obstruction) to investigate the relationship between coexisting hypoplasia and postnatally acquired cortical damage. Hypoplasia was assessed independently of the acquired cortical loss using medullary ray glomerular counting. Severe hypoplasia (glomerular number < 25% of normal) was detected in 47 of 86 patients. These patients underwent nephrectomy at a significantly younger age than those with minimal or no hypoplasia (P < 0.01). There was no significant relationship between the severity of hypoplasia and the presence or absence of obstruction. Severe acquired cortical loss was found in 68 of 86 patients. There was no significant association between the severity of cortical loss and the presence or absence of obstruction, age at nephrectomy or degree of coexisting hypoplasia. The findings suggest a strong association of hypoplasia and vesicoureteral reflux. Therefore, early postnatal presentation with minimal renal function need not necessarily reflect a failure of management but rather a pre-existing limitation of renal capacity. Furthermore, in a significant proportion of fetuses with ultrasonographic evidence of urinary tract abnormality, renal pathology may be present prior to the time at which in utero surgical intervention may be considered. PMID- 1457325 TI - Effects of enalapril on adriamycin-induced nephrosis. AB - Adriamycin induces proteinuria and glomerular changes in rats similar to those found in human focal segmental glomerulosclerosis (FSGS). Progression of this lesion may be slowed by use of angiotensin converting enzyme inhibition. To evaluate this we injected two groups of Sprague-Dawley rats with Adriamycin (2 intravenous doses of 2 mg/kg given at an interval of 3 weeks). One group of rats received enalapril (50 mg/l) in their drinking water. Control rats were injected with saline. After 28 weeks, the mean whole kidney glomerular filtration rate was significantly less and proteinuria and sclerotic index were significantly greater in rats receiving adriamycin compared with controls (P < 0.05). Administration of enalapril did not decrease proteinuria (545 +/- 398 mg/day vs 494 +/- 325 mg/day, P >0.05) or improve the glomerular filtration rate (0.31 +/- 0.18 ml/min per g kidney weight vs 0.41 +/- 0.21 ml/min per g, P = 0.27). However, treatment with enalapril significantly reduced the mean glomerular sclerotic index compared with untreated rats (1.62 +/- 0.88 vs 0.82 +/- 0.49, P = 0.05). Enalapril may be beneficial in preserving glomerular structure in this experimental model of FSGS. PMID- 1457327 TI - If the stimulus to pituitary thyroid-stimulating hormone (TSH) secretion is the lack of circulating free thyroxine (free-T4) why may a baby with congenital nephrotic syndrome present with a raised TSH on neonatal screening? PMID- 1457326 TI - Accelerated growth in short children with chronic renal failure treated with both strict dietary therapy and recombinant growth hormone. AB - In a 12-month study, nine boys, aged 4.8-15.6 years, with bone ages 4.6-13 years, with moderate to severe chronic renal failure and resultant growth failure were treated with daily recombinant human growth hormone (rhGH), in conjunction with a strict low-protein/low-phosphate diet supplemented with keto and amino forms of the essential amino acids, histidine and additional energy. Improved growth had previously been observed with this dietary management over that obtained with conventional treatment for chronic renal failure. Each child had been on this diet for at least 2 years before rhGH was commenced. Mean height velocity increased from 4.6 +/- 1.3 to 9.0 +/- 1.3 cm/year (P < 0.001) in the pre-pubertal group, and in the pubertal group from 5.4 +/- 1.4 to 10.4 +/- 1.8 cm/year (P < 0.01). The mean height velocity standard deviation scores (SDSs) increased from 1.2 +/- 0.6 to +2.3 +/- 0.9 (P < 0.001) in the pre-pubertal group and from -0.4 +/- 0.6 to +1.9 +/- 1.1 (P < 0.01) in the pubertal group. Mean height SDS for chronological age increased from -2.2 +/- 0.7 to -1.5 +/- 0.5 (P < 0.01) in the pre-pubertal group and from -1.9 +/- 0.7 to -1.3 +/- 0.9 in the pubertal group (P < 0.02). There was no significant deterioration in renal function or renal bone disease, and bone age did not advance more than chronological age over the 12 month period. PMID- 1457328 TI - Psychosocial adaptation of children and adolescents with chronic renal failure. AB - In a multicentre study comprising five paediatric nephrology centres in Western Germany, psychosocial and educational parameters were assessed (during 1987) in 479 children and adolescents with chronic renal failure (CRF) in order to gain insight into their psychosocial adaptation to the disease. At the time of assessment, 31% of patients were on conservative treatment, 14% on haemodialysis, 9% on continuous ambulatory peritoneal dialysis and 46% had a functioning transplant. The mean age at assessment was 13.6 years. Additional disabilities were noted in 29% of patients. School attendance of the 233 children of school age was in general satisfactory; 22% of patients attended schools for disabled or handicapped children. Vocational training was frequently inadequate, especially for dialysed patients, and only 14 of 53 adolescents over 16 years had graduated. Of 49 adult patients, only 21 were in some form of employment. A lack of age appropriate independence was observed in a large proportion (86%) of patients over 17 years, who continued to live with their parents or other persons taking care of them, whilst only 14% were living alone or with a partner. We conclude that, despite improved survival, psychosocial adaptation continues to be impaired in paediatric patients with CRF, especially in adolescents and those on dialysis. PMID- 1457329 TI - Altered in vitro lymphocyte response in childhood nephrotic syndrome. AB - The immune system, and disturbed T lymphocyte function in particular, has previously been implicated in the pathogenesis of childhood idiopathic nephrotic syndrome. As this disorder is commonly responsive to steroid therapy, we set out to determine whether in vitro suppression of lymphocyte blastogenic response to the mitogen phytohaemagglutinin (PHA) could predict the clinical situation. Comparing nine nephrotic children with nine healthy controls we were able to show the inhibitory prednisolone dose that suppressed lymphocyte blastogenesis by 50% (ID50) at a known concentration of PHA was significantly greater (P < 0.005) for nephrotic individuals. However, the in vitro assay did not reliably predict the clinical response to prednisolone. This study further implicates altered lymphocyte function in the mechanisms underlying idiopathic nephrotic syndrome. PMID- 1457330 TI - Lupus nephritis in a pediatric renal transplant recipient. AB - A case of aggressive lupus nephritis in a pediatric renal transplant patient is described. She initially presented with end-stage glomerulonephritis for which an underlying etiology could not be determined. Ten months after cadaveric renal transplantation, systemic lupus erythematosus was diagnosed, when she developed diffuse proliferative glomerulonephritis in association with antinuclear antibody, anti-double-stranded DNA antibody and extrarenal manifestations of lupus. It is plausible that she developed recurrent rather than de novo lupus nephritis following transplantation. Reactivation of lupus nephritis in a renal transplant is unusual in adults, and is previously unreported in children. PMID- 1457331 TI - If the stimulus to pituitary thyroid-stimulating hormone (TSH) secretion is the lack of circulating free thyroxin (free-T4), why may a baby with congenital nephrotic syndrome present with a raised TSH on neonatal screening? PMID- 1457332 TI - Practical peritoneal dialysis--the Tenckhoff catheter in acute renal failure. AB - The problem of acquiring secure peritoneal access encompasses most of the history of peritoneal dialysis. We review the catheters available for children and describe a simple method of insertion of Tenckhoff catheters for acute dialysis. Two series of Tenckhoff catheters inserted in this way are presented and compared with results obtained with trocar- and guidewire-inserted catheters. Tenckhoff catheters inserted as described allow significantly longer periods of dialysis (P < 0.02) with significantly fewer problem episodes (P < 0.001). We conclude that the use of the Tenckhoff catheter for acute dialysis, when inserted in the way described, confers significant advantages over other catheters and permits secure peritoneal access. PMID- 1457333 TI - Nephrogenic diabetes insipidus: clinical symptoms, pathogenesis, genetics and treatment. AB - This review summarizes various aspects of the inherited kidney disorder nephrogenic diabetes insipidus (NDI). The clinical manifestations of the disease are presented. The important role of the genetic localization of the NDI gene to the X-chromosome long arm, in region Xq28, for carrier detection and early (prenatal) diagnosis of the disorder is emphasized. Following an overview of the cellular physiology involved in the antidiuretic action of vasopressin, possible mechanisms in the pathogenesis of NDI are discussed. We hypothesize that NDI is most probably due to the absence or abnormality of the renal V2 receptor. This assumption is strengthened by recent findings in receptor studies, which indicate a general V2 receptor defect in NDI, and in experiments with somatic cell hybrid cell lines, which are consistent with a co-localization of the genes for NDI and for the V2 receptor in the Xq28 region. Finally, the efficacy of the combination amiloride-hydrochlorothiazide, compared with the indomethacin-hydrochlorothiazide regimen, in the treatment of NDI is presented and the advantages of the former combination are discussed. PMID- 1457334 TI - Renal effects of growth hormone. II. Electrolyte homeostasis and body composition. AB - Growth hormone (GH), either directly or through insulin-like growth factor-1 (IGF 1), has a wide spectrum of physiological and renal effects. This review concentrates on the effects of GH (derived from either pituitary or recombinant technology) and IGF-1 in three main areas: (1) sodium and water homeostasis; (2) calcium and phosphate balance, bone density and interactions with mineral regulating hormones; (3) fat and lean body mass. Observations of physiological changes in states of GH deficiency and excess in humans and animal models are presented. The lack of long-term toxicological data indicates that GH treatment for short stature in non-GH deficient children, with or without renal disease, should proceed with caution. PMID- 1457336 TI - An 18-year-old girl returns to continuous ambulatory peritoneal dialysis after a failed kidney transplant. PMID- 1457335 TI - The renal cytochrome P-450 arachidonic acid system. AB - In addition to cyclooxygenase and lipoxygenase, arachidonic acid (AA) is metabolized by the cytochrome P-450 monooxygenase system. The kidney is one of the major extrahepatic tissues that display cytochrome P-450 enzyme activities, in particular the cortex, specifically the proximal tubule demonstrate the highest concentration. AA is metabolized by the renal cytochrome P-450 epoxygenase and omega/omega 1 hydroxylases to epoxyeicosatrienoic acids and omega/omega-1 alcohols (20- and 19-mono-hydroxyeicosatetraenoic acids), respectively. These metabolites possess a broad spectrum of biological and renal effects which include: vasodilation, vasoconstriction, inhibition and stimulation of Na(+)-K(+)-ATPase, inhibition of ion transport mechanisms, natriuresis, inhibition of renin release and stimulation of cell growth. These metabolites are endogenous constituents of the kidney and are present in urine with increasing concentration under pathological conditions such as pregnancy-induced hypertension. The cytochrome P-450-dependent metabolism of AA is specifically localized to the proximal tubule and exhibits developmental changes, i.e., renal production of metabolites is very low in the fetus, newborn and up to 3 weeks of age, after which a remarkable increase in enzyme activities is observed. These characteristics call attention to the importance of this enzyme system in producing cellular mediators for regulating renal function in normal and diseased states. PMID- 1457337 TI - Clinical quiz. Addison's disease. PMID- 1457338 TI - Influenza in the world. 1 October 1991-30 September 1992. PMID- 1457339 TI - Interstitial photodynamic therapy in a rat liver metastasis model. AB - Photodynamic therapy (PDT) of hepatic tumours has been restricted owing to the preferential retention of photosensitizers in liver tissue. We therefore investigated interstitial tumour illumination as a means of selective PDT. A piece of colon carcinoma CC531 was implanted in the liver of Wag/Rij rats. Photofrin was administered (5 mg kg-1 i.v.) 2 days before laser illumination. Tumours with a mean (+/- s.e.) diameter of 5.7 +/- 0.1 mm (n = 106, 20 days after implantation) were illuminated with 625 nm light, at 200 mW cm-1 from a 0.5 cm cylindrical diffuser and either 100, 200, 400, 800 or 1600 J cm-1. Control groups received either laser illumination only, Photofrin only or diffuser insertion only. Short-term effects were studied on the second day after illumination by light microscopy and computer-assisted integration of the circumference of damaged areas. Long-term effects were studied on day 36. To determine the biochemistry of liver damage and function, serum ASAT and ALAT levels were measured on day 1 and 2, and antipyrine clearance on day 1. Tumour and surrounding liver necrosis increased with light dose delivered (P < 0.001). Best long-term results were obtained at 800 J cm-1 with complete tumour remission in 4 out of 6 animals. No deterioration in liver function was found. The results of this study show the ability of interstitial PDT to cause major destruction of tumour tissue in the liver combined with minimal liver damage. PMID- 1457340 TI - Epidermal growth factor receptor in ovarian tumours: correlation of immunohistochemistry with ligand binding assay. AB - Epidermal growth factor receptor (EGFR) was studied in ovarian tumours with immunohistochemical (IH) and ligand-binding assay (LBA). Two different monoclonal antibodies (MoAbs: 2E9, EGFR1) with respect to detecting EGFR with different ligand-binding affinities (low, high and low) were used. When comparing the IH data of MoAbs, 2E9 and EGFR1 a significant correlation was found (2P < 0.0001). Both antibodies stained 77% of the adenocarcinoma samples. The incidence of positivity as well as the mean percentage of stained cells was increased in metastases when compared with primary lesions. In 12.5% overexpression of EGFR (score 3) was noticed in some of the tumour cells. This was not due to amplification of the EGFR gene in any of the 25 ovarian tumours studied (including 6 which showed high expression of EGFR in IH). EGFR was detected in 66% of the adenocarcinomas analysed with LBA. A statistically significant correlation was found between the maximum binding capacities of EGFR obtained from Scatchard plots and the percentage of positive tumour cells determined by MoAb EGFR1 (2P < 0.0001). A weaker correlation was found between the reactivity of MoAb 2E9 and LBA (2P < 0.1). Clinical studies are necessary to determine the possible prognostic impact of EGFR determined with either method, or whether a combination of both will give a better discrimination between high- and low-risk patients. PMID- 1457342 TI - Vascular function and tissue injury in murine skin following hyperthermia and photodynamic therapy, alone and in combination. AB - The murine tail has been used as a model for injury to skin when hyperthermia (HT) and photodynamic therapy (PDT) using haematoporphyrin derivative, are used in combination. Skin injury by either agent alone was quantitated by the probability of tail necrosis as a function of dose of agent. 'Tolerance' doses of each modality were given and changes in skin vascular function were measured by the rate of clearance of 133Xenon. This was promptly inhibited but restored to normal by 7 days. The absolute numbers of hypodermal vessels of different sizes were measured in tail cross-sections and capillary numbers were found to be greatly reduced between 1 and 7 days, and restored to normal by 21-28 days. When a tolerance dose of PDT was followed at 1, 7, 21 and 28 days by test doses of HT, or vice versa, marked enhancements in probability of necrosis were observed when the interval was 1 or 7 days (Enhancement ratio (ER)PDT-HT = 1.5 and ERHT-PDT = 1.8). Prolonging the interval between modalities to 21-28 days spared the tissue (ERHT-PDT/21 DAYS = 1.1; ERPDT-HT/28 DAYS = 1.0). Close temporal apposition of PDT and HT, such as has been advocated to improve tumour control, may also increase injury to normal tissue through vascular effects common to both. PMID- 1457341 TI - Differential expression of cAMP-kinase subunits is correlated with growth in rat mammary carcinomas and uterus. AB - The expression of the regulatory (RI and RII) and catalytic (C) subunits of cAMP dependent protein kinase was found to depend on the growth-state in oestrogen dependent DMBA-induced mammary adenocarcinomas as well as in uteri of the rat. Castration-induced atrophy of the oestrogen-dependent tissues was accompanied by a decrease of the concentration of regulatory subunits (RI and RII) relative to both the catalytic subunit (C) and total protein, decreasing the R/protein and R/C ratios. A hyperplastic burst caused by high-dose oestrogen-replacement treatment was associated with an increased level of RI and little change in RII and C levels. Only minor differences were noted for the expression of mRNA for the alpha and beta subtypes of RI, RII and C between rat uteri from castrated and oestrogen-treated animals, or between mammary tumours from normal and castrated animals. Expression of RI beta-mRNA was detected only in the uterus. Our findings provide an experimental correlate for the reported value of the parameter R/protein in human mammary cancer biopsies to predict prognosis and outcome of therapy. Due to the sensitivity of the R/protein ratio towards changes in extracellular protein content, we recommend the biologically more meaningful R/C ratio in further clinical evaluations of mammary tumour biopsies. PMID- 1457343 TI - The anti-tumour effects of the prodrugs N-l-leucyl-doxorubicin and vinblastine isoleucinate in human ovarian cancer xenografts. AB - N-l-leucyl-doxorubicin and vinblastine-isoleucinate can be considered as relatively non-toxic prodrugs from doxorubicin and vinblastine, respectively. A comparative analysis was carried out of the anti-tumour activity of the four compounds as well as vintriptol in four human ovarian cancer xenografts different in histology, growth rate and chemosensitivity. Injections were given i.v. weekly twice into mice bearing well-established s.c. tumours. At equitoxic doses, the amount of drug administered for N-l-leucyl-doxorubicin and vinblastine isoleucinate was respectively 3-fold and 2-fold higher than the doses of the parent compound. N-l-leucyl-doxorubicin induced a growth inhibition > 50% in three out of four human ovarian cancer lines. The anti-tumour effects obtained were significantly better (P < 0.01) than in the case of doxorubicin. Vinblastine isoleucinate studied in two of these lines could induce a growth inhibition of > 50%. This prodrug appeared slightly less effective than vinblastine. Insignificant growth inhibition (< 50%) was obtained by vintriptol. PMID- 1457344 TI - 131I-meta-iodobenzylguanidine therapy in neuroblastoma spheroids of different sizes. AB - Mathematical models have predicted that targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (mIBG) is less likely to cure small rather than large micrometastases if 131I is the conjugated radionuclide. This study uses multicellular tumour spheroids as an in vitro model to test the hypothesis that smaller tumours of sub-millimetre dimensions are relatively resistant to 131I mIBG. Spheroids of the human neuroblastoma cell line SK-N-BE(2c), either 250 microns or 400 microns diameter, were incubated with 131I-mIBG at concentrations of up to 6.0 MBq ml-1. Using both regrowth delay and spheroid 'cure' as endpoints, the greater vulnerability of larger spheroids was confirmed. From this in vitro result we conclude that when used in vivo 131I-mIBG may spare smaller micrometastases. Therefore, either a radionuclide such as 211At which emits a shorter path length radiation should be conjugated to mIBG, or targeted radiotherapy should be combined with a treatment such as total body irradiation, the efficacy of which is not reduced in smaller tumours. PMID- 1457345 TI - Enhancement of the cytotoxicity of SR 4233 to normal and malignant tissues by hypoxic breathing. AB - The bioreductive cytotoxic agent SR 4233 (1,2,4-benzotriazine 3-amine 1,4 dioxide) has been shown to markedly potentiate the cell killing of mouse tumours when combined with fractionated radiation therapy. Differential metabolism under oxic compared to hypoxic conditions results in SR 4233 exhibiting selective cytotoxicity to hypoxic cells. This is thought to result from the production of a cytotoxic free radical which is generated predominantly in the absence of oxygen. We have examined a way of enhancing the effectiveness of this antitumour agent in vivo by artificially increasing the hypoxic fraction of tumours by hypoxic breathing. Mice are placed in a chamber containing 10% Oxygen 90% Nitrogen for 1 h after each administration of SR 4233. Our results in the SCCVII tumour model indicate that this manoeuvre results in a 10-fold increase in antitumour effectiveness of SR 4233 when administered in a fractionated regime with radiotherapy (8 x 2.5 Gy and 0.08 mmol kg-1), but not when a single treatment regime (1 x 20 Gy and 0.3 mmol kg-1) is used. Mathematical modelling of this effect is used to illustrate this phenomenon and can be used to predict the dependence of this type of therapy on the modification of tumour oxygenation. PMID- 1457346 TI - Increasing the effect of photodynamic therapy on the RIF-1 murine sarcoma, using the bioreductive drugs RSU1069 and RB6145. AB - The effect of combining photodynamic therapy (PDT) and bioreductive drugs has been investigated using the RIF-1 experimental murine tumour. Light was delivered interstially to the tumour at 675 nm using a single optical fibre attached to an argon-ion dye laser. The photosensitizer was disulphonated aluminium phthalocyanine (AlS2Pc) and the bioreductive drugs were the dual function nitroimidazole RSU1069 and its pro-drug RB6145. Varying the time between administration of the photosensitizer and light delivery (TL) from 30 min to 24 h had little influence on the extent of the anti-tumour effect of PDT alone, as measured by the regrowth delay endpoint. When the bioreductive drug was included in the treatment, administered 20 min before light irradiation, regrowth delay was greatly increased. The effectiveness of the combined treatment was optimum for short values of TL (about 1 h). Fluorescence microscopy was used to investigate the distribution of the photosensitizer within the tumours. This showed that the compound was mainly confined to the tumour vasculature over the first few hours post-treatment. The high efficacy of the combined treatment of PDT and bioreductive drugs for short values of TL suggest that photodynamic action, during the period when the photosensitizer AlS2Pc is confined to the vasculature, enhances the severity of tumour hypoxia which is sufficient to induce activation of the bioreductive drugs. PMID- 1457347 TI - Effects of staurosporine, K 252a and other structurally related protein kinase inhibitors on shape and locomotion of Walker carcinosarcoma cells. AB - The structure/activity relationship of the protein kinase inhibitors, staurosporine and K 252a and their analogues on motility of Walker carcinosarcoma cells has been studied in vitro. Staurosporine and K 252a, similar to phorbol myristate acetate (PMA) and diacylglycerols, suppress cell polarity and locomotor activity of Walker carcinosarcoma cells. Staurosporine inhibits spontaneous and colchicine-induced front-tail polarity (ID50 of about 6.0 x 10(-8) M) as well as spontaneous and colchicine-stimulated locomotion at 10(-7) M. K 252a suppresses cell polarity (ID50 of about 4.5 x 10(-6) M) and inhibits spontaneous and colchicine-stimulated locomotion at 10(-5) M, but suppression of locomotor activity is not complete in the presence of colchicine. CGP 41251, a staurosporine derivative with a much higher specificity for protein kinase C (PKC) than staurosporine, induces a dose-dependent increase in the proportion of polarised cells, and stimulates cell locomotion. Two K252a analogues, KT 5720 and KT 5822, which act preferentially on cyclic nucleotide-dependent protein kinases, and CGP 42700, an inactive staurosporine analogue, had no effect on cell polarity and locomotion. The findings suggest that protein kinase inhibitors acting preferentially on PKC may be of interest in pharmacological regulation of tumour cell locomotion. PMID- 1457349 TI - A model of multiple myeloma: culture of 5T33 murine myeloma cells and evaluation of tumorigenicity in the C57BL/KaLwRij mouse. AB - The 5T33 multiple myeloma is one of a series of transplantable murine myelomas arising spontaneously in C57BL/KaLwRij mice. This study describes the establishment and characterisation of the 5T33 murine myeloma in vitro as a cultured cell line in terms of its morphology, growth rate, expression of paraprotein (IgG2b) and tumorigenicity in syngeneic animals. The 5T33 cell line has been in continuous culture for over 10 months and has achieved more than passage 34. In culture, 5T33 myeloma grows as single cells or in small clusters of loosely adherent cells on an adherent stromal cell layer. Maximum doubling time is approximately 25 h, and over 90% of the cells express cytoplasmic IgG2b paraprotein. The cultured 5T33 myeloma cells are highly tumorigenic in C57BL/KaLwRij mice with as few as 500 cells inducing paralysis and death as early as day 36 post-tumour inoculation. Kinetics of tumour development and detection of IgG2b paraprotein are dose dependent. Two weeks following intravenous inoculation of 5 x 10(5) cultured 5T33 myeloma cells, tumour cells were readily identified in the bone marrow. By 3 weeks post-tumour inoculation, 5T33 myeloma cells were found in various tissues throughout the animal. Studies are now underway to determine the sensitivity of this cell line to various therapeutic modalities. PMID- 1457348 TI - Oestrogen receptor isoforms, their distribution and relation to progesterone receptor levels in breast cancer samples. AB - Oestrogen receptors (ER) in breast cancer tumours are highly heterogeneous. In this study, the variability in the profile of ER isoforms and its relation to progesterone receptor (PgR) levels in breast tumours has been studied. Using high resolution isoelectric focusing (IEF) 4 ER isoforms can be detected with pI values of 6.1 (corresponding to the 8S ER), and 6.3, 6.6 and 6.8 (all of which have a sedimentation pI values of 6.1 (corresponding to the 8S ER), and 6.3, 6.6 and 6.8 (all of which have a sedimentation coefficient of approximately 4S in sucrose density gradients). Data were obtained on the soluble receptors from supernatants of 66 ER-positive primary breast tumour homogenates using high resolution IEF. In 43 of these samples PgR levels were also measured. The isoform at pI 6.6 was present in 97.0% of tumours, the isoform at pI 6.1 in 83.3%, the pI 6.3 isoform 39.4% of tumours and the pI 6.8 isoform in only 33.3% of tumours. Only 12.1% of tumours studied contained the full complement of ER isoforms (pI 6.1, 6.3, 6.6 & 6.8). The ER isoforms at pI 6.1 & 6.8 were only found in PgR positive (> 10 fmol PgR/mg protein) tumours. Some tumours contained only a single ER isoform at pI 6.6 or 6.1, but those at pI 6.3 and 6.8 were never found singly. Tumours containing 3 or 4 ER isoforms had significantly higher levels of PgR (> 90 fmol/mg protein) than those with only 1 or 2 (P < 0.001). The presence of ER isoforms at pI 6.3 and pI 6.8 also significantly correlated with high levels of PgR (P < 0.001). This variability in the ER isoform profile of breast tumours and their correlation with PgR levels may have a bearing on prognosis and tumour response to endocrine therapy. PMID- 1457350 TI - Detection of RET oncogene activation in human papillary thyroid carcinomas by in situ hybridisation. AB - We have recently reported the activation of a new oncogene in human papillary thyroid carcinomas. This oncogene, named PTC, is a novel rearranged version of the ret proto-oncogene. In fact PTC is the product of the fusion of the tyrosine kinase domain of the ret proto-oncogene with the 5'-terminal region of another gene that we have named H4. The ret proto-oncogene shows a pattern of expression restricted to neuroendocrine tissue. Its fusion with H4 allows the expression of the activated form in thyroid papillary carcinomas. Therefore the detection of ret transcripts is a tool to investigate ret activation in thyroid neoplasms. Here we show the detection by in situ hybridisation, of activated ret transcripts in human thyroid papillary neoplasms that were positive for PTC activation by Southern blot analysis. We did not find any ret transcripts in papillary carcinomas negative for PTC activation, nor in normal thyroid and in non papillary thyroid neoplasias. PMID- 1457351 TI - Pixel-to-pixel correlation between images of absolute ATP concentrations and blood flow in tumours. AB - Iodo(14C-)antipyrine autoradiography and imaging bioluminescence have been combined to obtain pixel-to-pixel correlations between absolute values for local blood flow and ATP concentrations at a microscopical level within designated areas in hamster melanomas. Positive pixel-to-pixel correlations were obtained in 4 of 6 tumours. Both flow and ATP values were less in mostly necrotic than in mostly viable tumour regions. The data provide evidence for the energetic state of cancer cells being strongly influenced by the efficiency of tumour microcirculation in several but not in all malignancies investigated. PMID- 1457353 TI - Intra-hepatic-arterial infusion of misonidazole--an experimental study of regional radiosensitisation by intraarterial embolisation. AB - The purpose of this study was to generate a selective radiosensitising effect by the intra-hepatic-arterial infusion of misonidazole (MISO). MISO (10 mg) was infused after transcatheter hepatic-arterial embolisation into the livers of rabbits bearing VX2 liver cancer. This procedure was followed by 15 Gy electron irradiation. Evaluation of tumour volume and histological examination was carried out on the 7th day after treatment. The greatest tumour response was obtained in the group which received MISO followed by radiation and was characterised by extensive fibrosis around the tumour and nearly complete tumour necrosis. Liver cell regeneration was also noted in adjacent liver tissue. The advantages of regional infusion of MISO following hepatic-arterial embolisation are: (1) Selectivity increased radiosensitivity of liver cancer alongside very low drug concentration in the plasma. (2) Reduced or absent deleterious side effects of MISO with higher tumour/normal tissue ratios of drug concentration. (3) Reduced cost due to the lower dosage of MISO required for regional infusion. PMID- 1457352 TI - Reduced drug accumulation as a major mechanism of acquired resistance to cisplatin in a human ovarian carcinoma cell line: circumvention studies using novel platinum (II) and (IV) ammine/amine complexes. AB - Acquired resistance to cisplatin (cis-diamminedichloroplatinum (II)) has been generated in vitro in the 41M human ovarian carcinoma cell line, established from a previously untreated patient. Three cisplatin-resistant variants were selected at approximately 2, 4 and 6-fold resistance (in terms of 50% inhibitory concentrations), in order to study the underlying mechanisms of acquired cisplatin resistance. Compared to the parent line, platinum accumulation following exposure to equimolar concentrations of cisplatin was on average (across the entire concentration range) 2.9, 3.6 and 4.8-fold lower in the 41McisR2, 41McisR4 and 41McisR6 cell lines, respectively. Thus the difference in uptake corresponded closely with their resistance factor in the three resistant variants. Moreover, a significant reduction in platinum accumulation was observed as early as 5 min after exposure to cisplatin in the 41M vs 41McisR6 cell lines. Platinum accumulation was similar in all cell lines following exposure to equitoxic concentrations (2 h IC50) of cisplatin. Enhanced efflux of drug was not observed between the 41M and 41McisR6 cells. In addition, there was no difference in intracellular glutathione (GSH) levels. Our previous studies have shown no indication of metallothionein involvement and the decrease in cisplatin uptake in the 41McisR6 cells was reflected by a similar reduction in DNA interstrand cross links (ISC) formation. These results suggest that the mechanism of acquired resistance to cisplatin in the 41McisR6 cell line may be predominantly due to reduced drug uptake. The 41McisR6 cells were not found to be cross-resistant to ouabain, a postulated specific inhibitor of sodium-potassium adenosine triphosphatase (Na+, K(+)-ATPase), suggesting that decreased cisplatin accumulation in these cells is probably not regulated by alterations in their Na+, K(+)-ATPase levels, and Na+ potential across the plasma membrane. Cellular accumulation of a novel class of platinum (IV) ammine/cyclohexylamine dicarboxylates, which exhibit enhanced cytotoxicity over cisplatin and completely circumvent resistance to cisplatin in the 41McisR line, was also examined. The data suggests that increased accumulation of these compounds, as a result of their enhanced lipophilicity, could account for the dramatic increase in their potency over cisplatin. PMID- 1457354 TI - Kaposi's sarcoma in England and Wales before the AIDS epidemic. AB - The epidemiological features of Kaposi's Sarcoma (KS) incidence in England and Wales in the period 1971-1980 are reviewed. The epidemiology of KS in England and Wales in this period is distinct from that associated with the AIDS epidemic. The incidence was probably very low compared to other Western countries, there was little male excess, and no indication, based on marital status data, of a raised incidence in male homosexuals. Half the cases registered were in people born outside the UK. The region of birth distribution in these migrants reflected the known pre-AIDS geographic distribution of KS and also pointed to high risks in those from Middle Eastern countries and the Caribbean. The very low incidence rates of KS in natives of England and Wales suggests that the background prevalence of the causative agent for KS was low in England and Wales prior to the AIDS epidemic. PMID- 1457355 TI - Confidentiality in the cancer registry. PMID- 1457356 TI - Oestrogen receptor protein and mRNA in adenocarcinoma of the uterine cervix. AB - We have investigated the oestrogen receptor (ER) status of 20 cervical adenocarcinomas by immunocytochemistry for ER protein and non-isotopic in situ hybridisation for ER mRNA. Both methods, which are applicable to paraffin sections, were developed and validated in breast carcinomas with known ER content. Six cervical adenocarcinomas contained immunocytochemically demonstrable ER protein; all contained ER mRNA, but staining was less intense in poorly differentiated areas of four tumours. This disparity between protein and mRNA detection needs further investigation as does the possibility that oestrogens may play a role in the pathogenesis of cervical adenocarcinoma. PMID- 1457357 TI - Outcome of children with resistant and relapsed Hodgkin's disease. AB - During the period 1974-89, 169 children with Hodgkin's disease were treated in the Paediatric Oncology Units of the Royal Marsden and St Bartholomew's Hospitals. The overall actuarial survival for the whole group was 81% at 10 years. Thirty-five of the 169 children either did not achieve a complete remission or subsequently relapsed. The estimated actuarial survival from initial relapse or failure of primary treatment was 60% at 5 years and 45% at 10 years. Over half of the patients requiring salvage therapy had declared themselves within 2 years and only 3 relapses occurred more than 3 years from diagnosis. Very few patients remain disease free long term after failure of primary and initial salvage therapy. Patients relapsing within a year of diagnosis or not achieving a complete response to primary therapy and those with disseminated relapse had a poor response to salvage therapy. A significant subgroup of patients had prolonged survival despite multiple relapses. Neither initial histology nor stage affected survival from relapse although numbers in each subgroup were small. PMID- 1457358 TI - Beta-carotene supplementation in smokers reduces the frequency of micronuclei in sputum. AB - beta-carotene has been hypothesised to reduce lung cancer risk. We studied the effect of 14 weeks of beta-carotene supplementation (20 mg d-1) on the frequency of micronuclei in sputum in 114 heavy smokers in a double-blind trial. Micronuclei reflect DNA damage in exfoliated cells and may thus provide a marker of early-stage carcinogenesis. Pre-treatment blood levels of cotinine, beta carotene, retinol and vitamins C and E were similar in the placebo group (n = 61) and the treatment group (n = 53). Plasma beta-carotene levels increased 13-fold in the treatment group during intervention. Initial micronuclei counts (per 3,000 cells) were higher in the treatment group than in the placebo group (5.0 vs 4.0, P < 0.05). During intervention, the treatment group showed a 47% decrease, whereas the placebo group showed a non-significant decrease (16%). After adjustment for the initial levels, the treatment group had 27% lower micronuclei counts than the placebo group at the end of the trial (95% CI: 9-41%). These results indicate that beta-carotene may reduce lung cancer risk in man by preventing DNA damage in early-stage carcinogenesis. PMID- 1457359 TI - Is liver to lung shunting in colorectal liver metastasis the cause of toxicity following treatment with cytotoxic microsphere aggregates? AB - Incorporation of cytotoxic drugs into microspheres reduces but does not eliminate systemic toxicity. The extent of liver to lung shunt was measured in 26 patients with colorectal liver metastasis. Liver to lung shunting correlated with proportion of liver replacement but did not exceed 4.4% and therefore is unlikely to cause systemic toxicity. PMID- 1457360 TI - The combination of radiotherapy, adjuvant chemotherapy (cyclophosphamide doxorubicin-ftorafur) and tamoxifen in stage II breast cancer. Long-term follow up results of a randomised trial. AB - Two hundred patients with node positive stage II breast cancer were randomised to four groups after radical mastectomy and axillary evacuation: (1) Postoperative radiotherapy, (2) Adjuvant chemotherapy with eight courses of CAFt (cyclophosphamide 500 mg m-2 + doxorubicin 40 mg/m-2 + ftorafur 20 mg kg-1 orally day 1-14) every fourth week, (3) Postoperative radiotherapy and adjuvant chemotherapy and (4) postoperative radiation, adjuvant chemotherapy and tamoxifen 40 mg daily for 2 years. Thirty-two per cent of the patients discontinued treatment due to GI-toxicity, while 26% required dose reductions due to leukopenia. Radiation pneumonitis was more frequent after the combination of postoperative radiotherapy with chemotherapy. There was a better relapse-free survival in the groups receiving chemotherapy compared to radiotherapy alone (P = 0.05), which was highly significant in a multivariate Cox analysis (P = 0.004). No significant survival differences were seen. Tamoxifen had no clear overall effect but there were better relapse-free (P = 0.04) and overall (P = 0.004) survival with tamoxifen in estrogen receptor positive patients, while estrogen receptor negative patients had a somewhat poorer survival (P = 0.07) after tamoxifen. Local control was better (NS) after the combination (93%) radiotherapy and chemotherapy compared to either treatment alone (76% with radiotherapy and 74% with chemotherapy at 5 years). PMID- 1457361 TI - Peripheral blood lymphocyte number and phenotype prior to therapy correlate with response in subcutaneously applied rIL-2 therapy of renal cell carcinoma. AB - The phenotype of peripheral blood lymphocytes of 27 renal cell carcinoma patients before and at the end of subcutaneously given rIL-2 therapy was determined by two colour flow cytometry. Therapy induced changes in peripheral blood leucocyte composition and phenotypes were comparable to those reported for intravenously given rIL-2. The present paper shows a correlation between the 'activation status' of the patient before therapy and eventual response. PMID- 1457363 TI - Interleukin 2 therapy in cancer: identification of responders. AB - C-reactive protein (CRP) levels in serum were measured in fifteen patients with metastatic colorectal carcinoma, prior to and during treatment with a continuous intravenous infusion of rIL.2. Patients were subsequently classified as responders or non-responders to this therapy. Baseline serum CRP levels, prior to treatment, were significantly lower in the responders (range < 2-8 mg l-1) when compared with the non-responders (range 7.5-116 mg l-1), P = 0.004. Furthermore, the responding patients demonstrated significantly and grossly elevated CRP stimulation indices (SI) compared with non-responders at different time intervals during the rIL2 infusion. At the cessation of rIL2 therapy, the CRP stimulation index was 31.3 +/- 9.3 in the responders, and only 1.6 +/- 0.3 in the non responders (means +/- s.e.m, P = 0.014). These findings suggest that it is possible to predict those cancer patients who are most likely to respond to and benefit from rIL2 therapy, either prior to the commencement of or during the first course of rIL2. PMID- 1457362 TI - The association of body size, reproductive factors and thyroid cancer. AB - A population-based case-control study of the association of diet and other factors and thyroid cancer was conducted between 1980 and 1987 on Oahu, Hawaii. Study participants included 51 men and 140 women with thyroid cancer, and 113 male and 328 female controls matched on age (+/- 5 years) and sex. A significant, positive monotonic dose-response relation of weight in late adulthood (5 years prior to interview) and the risk for thyroid cancer was found for men and women. A greater than five-fold increase in the risk for thyroid cancer among men, and more than a two-fold increase in risk among women, was found for subjects in the highest compared with the lowest quartile of weight in late adulthood. Height was significantly related to the risk for thyroid cancer among men, but not women. Among men, there was a significant dose-response relation of weight in early adulthood (20-29 years of age) and the odds ratios (ORs) for thyroid cancer, although the trend was not significant after adjustment for height. Among women, there was also a positive relation of adult weight gain and thyroid cancer, with an OR of 2.6 associated with more than a 14% increase in weight. The effects of relative weight and weight gain on thyroid cancer risk were stronger in post menopausal women than in premenopausal women. There was a significant positive interaction between fertility drug use and early adult weight and the risk for thyroid cancer in women. Odds ratios were also significantly elevated for women above the median weight in early adulthood who experienced a miscarriage or stillbirth at first pregnancy. In summary, these data show an association of weight, particularly in late adulthood, and the risk for thyroid cancer in men and women, and further suggest a positive interaction between weight in young adulthood and fertility drug use on thyroid carcinogenesis in women. PMID- 1457364 TI - Expression of metalloproteinases and their inhibitors in primary pulmonary carcinomas. AB - Nine primary pulmonary carcinomas, one metastatic carcinoma, and two malignant pleural mesotheliomas have been analysed for the expression at the mRNA level of metalloproteinases (MPs) and tissue inhibitors of MPs (TIMPs). In situ hybridisation showed TIMP-1 and TIMP-2 transcripts predominantly over tumour stroma and gelatinases evenly distributed over both stromal and tumour cells. While both TIMP-1 and TIMP-2 were expressed in non-neoplastic lungs (NNL) as well as in carcinomas, stromelysin 3 (ST3), 92 kDa gelatinase and interstitial collagenase were expressed only by carcinomas. Expression of these MPs by carcinomas was independent of histologic type and such tumour features as fibrosis or necrosis. The consistent expression of ST3 by all of the carcinomas examined and absence of its expression in NNL indicates that ST3 production is likely associated with the malignant phenotype. However, since 92 kDa gelatinase and interstitial collagenase transcripts were found in some but not all tumour samples, their expression is not a uniform feature of pulmonary carcinomas. The possible prognostic significance of the expression of the latter two enzymes by carcinomas remains to be established. PMID- 1457365 TI - Alcohol and cancer. PMID- 1457366 TI - Malignant neoplasms associated with cancer of the ampulla of Vater. PMID- 1457367 TI - Adjuvant therapy in resectable gastric cancer. PMID- 1457368 TI - IL2 treatment for cancer: from biology to gene therapy. AB - In this review we shall discuss the biological rationale and the clinical findings obtained using Interleukin 2 (IL2)-based immunotherapy in the management of cancer patients. Objective and long-lived clinical responses have been documented in a proportion of cases, particularly renal cell carcinoma, melanoma and acute myeloid leukaemia. Though encouraging, the clinical use of IL2 has so far been limited by toxicity, as well as by the heterogeneous and unpredictable responses and by the lack of specific anti-tumour effect. These considerations have led to the belief that more sophisticated technologies aimed at introducing the IL2 gene into the neoplastic cells may potentially overcome some of the limitations coupled to the in vivo infusion of high doses of IL2. The data accumulated in animal models and, more recently, also with human tumour cells indicate that the IL2 gene may be successfully inserted into neoplastic cells. The constitutive secretion of IL2 by the tumour cells leads to a reduced or abrogated tumorigenicity in several different tumour models. The evidence that in some experimental tumours the transduction of the IL2 gene into the neoplastic cells may elicit a specific cytotoxic response and confer anti-tumour memory, suggests that vaccination protocols based on this innovative strategy may represent a potential new tool in the management of cancer patients. PMID- 1457369 TI - Intrathecal chemotherapy with ACNU for meningeal gliomatosis. AB - ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride], one of the chloroethylnitrosoureas (CENUs), is believed to be effective against malignant glioma when intravenously or intrathecally administered. A rat model with meningeal gliomatosis (MG) induced by an intracisternal inoculation of rat C6 or 9L glioma cells was intrathecally and intravenously treated with ACNU in order to test the feasibility of intrathecal chemotherapy with ACNU in the treatment of meningeal gliomatosis. The median survival time (MST) of the animals was significantly prolonged when ACNU was intrathecally administered at dosages of 0.5 to 1.5 mg kg-1 in the early stages of MG, i.e. within 3 days after the tumour inoculation, whereas intravenous therapy with ACNU at a dose of 15 mg kg-1 did not exhibit any efficacy in the rats inoculated with C6 glioma cells (C6-MG). Intrathecal ACNU, however, at dosages of up to 1.5 mg kg-1 failed to demonstrate any therapeutic effect in the late stage of MG, i.e. 5 days after the tumour inoculation, except in the rats inoculated with 9L brain tumour cells (9L-MG). Intravenous chemotherapy with ACNU at a dose of 15 mg kg-1 extended the MST of the 9L-MG rats more significantly in the late stage of MG than in its early stage. This points to the feasibility of intrathecal ACNU in the treatment of meningeal gliomatosis in its early stages, but not in its late stages in which intravenous ACNU might be more effective than intrathecal treatment against MG of which the parenchyma has already been deeply invaded by the tumour. PMID- 1457370 TI - Fibrous dysplasia of the skull in children. AB - Early diagnosis of skull fibrous dysplasia in children is relatively easy, based on a history of painless progressive bony bulging. The therapeutic approach is still controversial, due to the benignity of the lesion. However, the clinical course may be unpredictable, with sudden appearance of symptoms, some of which can be important and irreversible. In pediatric patients, the possibility that an early surgical correction might positively interfere with the natural history of the lesion has to be evaluated by taking into account the obvious difficulties that will be encountered in reconstructing the skull after a wide excision of the pathologic bone. In the present report, we describe our personal experience on the surgical treatment of 9 children, ranging in age between 7 and 14 years. The patients were subdivided into two groups, according to the localization and extent of the disease. Patients in group 1 presented an involvement of the hair covered cranium and/or the fronto-orbital region. Group 2 patients presented with a multizonal involvement of the skull, including the central cranial base (pterygoid, sphenoid, petrous and mastoid bone). The different surgical options, chosen for the two groups of patients, are discussed, together with the technical methodologies utilized, the cosmetic results and the long-term follow-up. PMID- 1457371 TI - Time course of intraventricular pressure change in a canine model of hydrocephalus: its relationship to sagittal sinus elastance. AB - Hydrocephalus was induced in adult greyhounds by intracisternal kaolin. Intraventricular pressure (IVP) was monitored in the conscious animal for 2 weeks using a small implantable sensor, and the time-course of IVP change was characterized. Intraventricular pressure increased significantly within 36 h of kaolin infusion and gradually subsided to normal values within 1 week. Enlargement of the lateral ventricles was not observed during the early phase of intracranial hypertension (less than 2 days). Evolving hydrocephalus and intracranial hypertension increased the elasticity (dP/dV) of the sagittal sinus. This effect was statistically significant (p < 0.05) and is possibly reversible in the acute stage. Normotensive hydrocephalus (1 and 2 weeks after kaolin) was associated with an irreversible increase in resistance to outflow (i.e., increased sagittal sinus elasticity). Sagittal sinus venography of animals with obvious ventricular enlargement (at least 1 week after kaolin) showed development of venous collaterals and atypical outflow pathways. PMID- 1457372 TI - Biopsy diagnosis of familial Alexander's disease. AB - A 26-year-old woman presented with headaches, incoordination and a cerebellar mass (1982). The CT scan revealed dilated ventricles and a hypodense space occupying lesion adjacent to the fourth ventricle. Neuronal loss, gliosis and masses of Rosenthal fibers were seen in biopsy. There was no evidence of neoplasm. A second biopsy 2 years later was similar to the original specimen. A diagnosis of Alexander's disease was suggested. Later that year the patient's 11 year-old brother manifested a clinical picture initially diagnosed as brainstem glioma, but whose biopsy was characteristic of Alexander's disease. There has been a gradual deterioration of these siblings over the past 6 years (1986-1991). No evidence of neoplasm has appeared. PMID- 1457373 TI - The Vater association and spinal dysraphia. AB - We here present a hereto previously undescribed association of occult spinal disorders of the distal spinal cord/filum in the Vater association. We present 6 patients who were diagnosed as having the Vater association who subsequently presented with occult spinal disorders, primarily lipomas of the filum/conus complex with or without subcutaneous lipomas. Uniformly the spinal cord was tethered to the lipoma/filum complex. Progressive neurological dysfunction was noted in those in whom the diagnosis was made late in the disease. The importance of neuroimaging of the distal spinal canal, in children in whom the diagnosis of the Vater association has been made, is emphasized to prevent insidious neurological damage if not already present. PMID- 1457374 TI - Perinatal spinal cord injury: clinical, radiographic and pathologic features. AB - Perinatal spinal cord injury is a relatively uncommon, but a frequently misdiagnosed disorder. Often, the injury is not suspected and an erroneous diagnosis is made. We present five cases of perinatal spinal cord injury. In four, the referring physicians (including pediatric neurologists) misdiagnosed the condition. In view of these diagnostic difficulties, we review the clinical, radiographic and pathologic aspects of these injuries. Serious spinal injuries occasionally occur in the perinatal period. With improving medical care, many infants with less severe injuries are surviving the neonatal period. Therefore, the prompt recognition of neonatal spinal cord damage is essential and allows for optimal treatment of the injured child. PMID- 1457375 TI - Osteoplastic laminotomy in children. AB - The article reviews 180 cases of osteoplastic laminotomies, 1 year after operation. The patients were predominantly children undergoing selective dorsal rhizotomies. Also included were a few pediatric patients who received laminotomies for spinal cord tumors. Spinal X-rays were reviewed at 1 and 3 years of follow-up. There was complete to partial bridging of the laminar roof in all cases. This experience confirms that the procedure is well tolerated and is associated with reossification of the replaced bony segment. PMID- 1457376 TI - How to reduce the morbidity of wound closure following extensive and complicated laminectomy and tethered cord surgery. AB - Prior irradiation and surgery predispose laminectomy wounds to a higher than usual incidence of wound problems. Likewise the tightness or absence of local fascia in the tethered cord patient make wound closure more complicated. To reduce morbidity, i.e., CSF leak or pseudomeningocele formation, specific techniques are required. These methods are outlined below. PMID- 1457377 TI - Removal of adherent ventricular catheter. AB - The technique for freeing adherent ventricular catheters is described in which a Bugbee wire, insulated except for the tip, is used to deliver a monopolar coagulating current to the tissue adherent to the drainage holes of the catheter. This may have some advantage over the use of an uninsulated metal cannula for delivery of a unipolar diathermy cutting current. The technique described has permitted effective and safe removal of adherent ventricular catheters. PMID- 1457378 TI - IGF-2 stimulates growth and metabolism of early mouse embryos. AB - Recent reports indicate that the insulin gene family plays a significant role in early development. Both insulin and IGF-1 stimulate growth and metabolism in preimplantation mouse embryos, however, little is known of the physiological effects of IGF-2. In this study, addition of IGF-2 to defined culture medium for the culture of 2-cell embryos stimulated blastocyst formation by 15%, ICM mitogenesis by 37%, and protein synthesis by 35%. EC50s of 12-63 pM IGF-2 for these responses were in the range for mediation by IGF-2 receptors. These results coupled with the previously demonstrated presence and expression of the IGF-2 receptor from the 2-cell stage supports a role for this third member of the insulin gene family in early development. PMID- 1457379 TI - Over-expression of fibroblast growth factors in Xenopus embryos. AB - A number of forms of fibroblast growth factor (FGF) were over-expressed within Xenopus embryos by injection of synthetic FGF mRNAs into fertilized eggs. Injected embryos showed abnormalities in development which were mainly secondary to a disruption of gastrulation movements. The effects observed after injection of bFGF mRNA, however, were much less severe than those observed after injection of an altered form of bFGF mRNA which differs only by the addition of a signal sequence for secretion, or of another member of the FGF family, kFGF, which is normally efficiently secreted. All forms of FGF caused the induction of mesoderm in animal cap explants isolated from blastulae, but the amount of bFGF mRNA required to induce the formation of significant levels of mesoderm was higher by a factor of over a hundred than that of the FGFs which contain a signal sequence for secretion. Over-expressed bFGF accumulated in the nuclei of blastulae but did not necessarily cause mesoderm formation. These results show that FGFs must be secreted from the cells in which they are synthesised in order to act efficiently as mesoderm inducing factors and suggest that bFGF itself, which does not contain a signal sequence for secretion, is unlikely to be directly involved in mesoderm induction during early embryonic development. PMID- 1457380 TI - Ectopic expression of the Drosophila tramtrack gene results in multiple embryonic defects, including repression of even-skipped and fushi tarazu. AB - The tramtrack (ttk) gene of Drosophila encodes 69-kDa and 88-kDa proteins through alternative splicing of the primary ttk transcript. The two proteins share a common amino-terminal sequence, but contain different carboxy-terminal portions, each of which has a distinct zinc finger domain with a unique DNA binding specificity. The 69-kDa ttk protein has been shown to bind multiple sites within important regulatory elements of the pair-rule genes even-skipped (eve) and fushi tarazu (ftz), and it has been suggested that this protein may function as a repressor of ftz transcription. Here we present evidence that the 69-kDa ttk protein can indeed repress expression not only of ftz, but also of eve. Ectopic expression of the 69-kDa protein, but not of the 88-kDa form, was found to nearly abolish the striped patterns of expression of both eve and ftz in transgenic embryos. These findings, coupled with our detection of significant levels of ttk protein in ovaries and 0-2-h embryos, support the idea that maternally supplied ttk protein serves to prevent premature activation of eve and ftz, thereby helping to establish the timing of the onset of zygotic expression of these two genes. Furthermore, gross defects in the larval cuticle resulting from misexpression of the 69-kDa protein suggest that this protein performs additional functions in the early embryo. PMID- 1457381 TI - Comparative analysis of Pax-2 protein distributions during neurulation in mice and zebrafish. AB - Members of different vertebrate species share a number of developmental mechanisms and control genes, suggesting that they have similar genetic programs of development. We compared the expression patterns of the Pax-2 protein in Mus musculus and Brachydanio rerio to gain a better understanding of the evolution of developmental control genes. We found that the tissue specificity and the time course of Pax-2 expression relative to specific developmental processes are remarkably similar during the early development of the two organisms. The brain, the optic stalk, the auditory vesicle, the pronephros, and single cells in the spinal cord and the hindbrain express Pax-2 in both species. The Pax-2 expression domain in the prospective brain of E8 mouse embryos has not been described previously. Expression appears first during early neurulation at the junction between the midbrain and hindbrain. However, there are some differences in Pax-2 expression between the two species. Most notable, expression at the midbrain/hindbrain boundary is no longer detectable after E11 in the mouse. Using monoclonal antibodies, we could exclude that primary neurons express Pax-2 in the zebrafish spinal cord. Our results confirm that Pax genes are highly conserved both in sequences and in expression patterns, indicating that they may have a function during early development that has been conserved during vertebrate evolution. PMID- 1457382 TI - An early molecular component of the wound healing response in rat embryos- induction of c-fos protein in cells at the epidermal wound margin. AB - The spreading of epithelial sheets plays a pivotal role in normal embryonic morphogenesis but the cellular and molecular mechanisms underlying these processes are not very well understood. One way of directly examining epithelial spreading in the embryo is to excise a piece of tissue and follow the epithelial wound healing process. In this paper we report our studies of the healing of a simple excisional lesion to the E12.5 rat embryo hindlimb. The wounded, living embryo is cultured in a roller bottle and under such conditions the lesion is completely re-epithelised by 24 h. We find that epidermal cells specifically at the margin of the wound rapidly (within 15 min of wounding) and transiently express the nuclear transcription factor c-fos. This induction occurs whether or not serum is included in the culture medium. We speculate that local induction of c-fos at the wound site may play a role in regulating transcription of genes involved in the healing process. PMID- 1457383 TI - Computer-aided classification of malignancy in astrocytomas. I. The value of nuclear parameters obtained by automated black and white image analysis. AB - Ninety-three selected cases of astrocytomas including glioblastomas (astrocytomas grades 1-4) were evaluated by means of Feulgen-stained microscopic slides for nuclear parameters obtained by automated black and white image analysis (ABWIA). The goal was to determine to what extent nuclear features evaluated by ABWIA were applicable as classifiers for the computer-aided numerical classification of malignancy in astrocytomas. Before the automated evaluation, all tumours had been subjectively graded according to the Mayo Clinic grading rules as delineated by Ringertz. Twenty-three nuclear parameters were evaluated and tested for their classification impact. With a model of five parameters (number of nuclei per area, mean of the convex form factor, extinction sum, extinction variation, and full-width-half-maximum of the extinction distribution) the highest reclassification rate of 75% correctly reclassified cases was obtained. Although this is a good result for a classification using only nuclear parameters, it is too poor for practical application. Thus, nuclear parameters evaluated by ABWIA alone are insufficient for numerical classification models assessing the malignant expression of astrocytomas. PMID- 1457384 TI - Computer-aided classification of malignancy in astrocytomas. II. The value of categorically evaluated histologic and non-histologic features for a numerical classifier. AB - The present study was carried out in order to obtain a numerical classifier for the assessment of the malignancy in astrocytomas including glioblastomas ('astrocytomas grade 4'). The attempt resulted in 'TESTAST 268', a classifier based on a reference sample of 268 tumours, 67 in each of four malignancy classes. TESTAST 268 aids the identification of astrocytomas with one of four malignancy classes by means of eight classification variables, five histologic and three non-histologic. Identification is achieved with the aid of linear discriminant functions, both according to Bayes' decision rule (BAYTEST) and by canonical discriminant analysis (CANTEST) using the squared Mahalanobis distance. The discriminant functions with the calibration of the reference sample of the 268 tumours may be implemented on personal and even small pocket computers for practical application. PMID- 1457385 TI - Can chromatin texture predict structural karyotypic changes in diploid cells from thyroid cold nodules? AB - To assess the effect of a single chromosomal translocation on the nuclear phenotype of human cells, seven diploid adenomas and five diploid carcinomas of the thyroid gland were studied using quantitative nuclear morphometry. Four adenomas and three carcinomas were cytogenetically normal, whereas three adenomas and two carcinomas had a unique chromosomal translocation. A densitometric parameter discriminated adenomas from carcinomas (skewness of the optical density histogram, SODH), and tumours with and without chromosomal translocation (standard deviation of the optical density, SDODH). These results demonstrate that single chromosomal structural rearrangements produce quantifiable alterations of nuclear organisation, but that other nuclear features which do not express an aneuploid DNA content or an abnormal karyotype differentially characterise benign and malignant conditions. PMID- 1457386 TI - A morphometric filter improves the diagnostic value of morphometric analyses of frozen histopathological sections from mammary tumours. AB - Frozen sections of 202 consecutive breast tumour cases were analyzed by morphometric quantitation of nuclear features. Nuclei were selected at random. Conventional light microscope examination of the paraffin-embedded specimens revealed 144 cases of cancer and 56 benign tumours. Using multivariate discriminant analysis of morphometric features, all but two of the benign cases and 79% of the malignant tumours were correctly classified. When a morphometrically based dynamic filter set to exclude 'non-diagnostic' nuclei was used, the correctly classified malignant cases rose to 86% Morphometry is a fast, reproducible and efficient method that can be used in conjunction with the histomorphological diagnosis of mammary frozen sections. The combination of systematic sampling and an objective dynamic filter may be a powerful approach to quantitative analyses of tumours from other sites. However, it is also likely that efficiency can be improved by combining nuclear morphometric features with structural, histochemical and molecular biological data. The combination of traditional histomorphological examination with quantitative information may well increase the diagnostic accuracy in individual patients. PMID- 1457387 TI - How often is dysplasia diagnosed by biopsy or smear examination? Application of a maximum likelihood based method to the assessment of detection rates in the nasal mucosa of nickel workers. AB - In view of the known increased risk of nasal carcinoma and the high prevalence of dysplastic lesions of the nasal mucosa among nickel workers, regular screening for the existence of possibly precancerous dysplastic lesions is offered to workers in a Norwegian nickel refinery. Unfortunately, available sampling techniques do not allow the identification of all subjects in whom dysplastic changes are present. Independent histological and cytological (brush cytology) diagnoses, obtained for each of a group of 90 workers, have been used to estimate, by a maximum likelihood method, the probabilities that existing dysplastic lesions will be detected by each of these two screening methods. In the group studied, cytology performed rather less well than histology in unambiguously detecting dysplasia. However, when cytological specimens showing irregular (possibly dysplastic) epithelial cells were grouped with those showing clear dysplastic changes, detection probabilities were estimated at 0.52 by histology and 0.57 by cytology. Detection probabilities were estimated to be higher among subjects with a previously known history of dysplasia, particularly by histology (P < 0.01), probably due to larger dysplastic areas. In view of both its greater facility and speed of sampling, and its greater acceptability, brush cytology may be preferable to biopsy sampling for the screening of large numbers of workers at risk. PMID- 1457388 TI - The determination of the steady-state pharmacokinetic profile of fluphenazine decanoate by gas chromatography/mass spectrometry detection. AB - This study uses the highly sensitive method of gas chromatography/mass spectrometry to compare the basic steady-state pharmacokinetic parameters of two fluphenazine decanoate formulations. Sixteen stable outpatients participated in a two-way crossover design study of the bioavailability of a new formulation of FPZ Dec, i.e., 10 mg/ml, to the standard 25 mg/ml formulation. When compared to a 1 ml injection of the standard formulation (25 mg/ml) over a two-week, steady-state period, we found bioequivalence as evidenced by similar mean areas under the curve (hrs x ng/ml). We did find that the injection volume of the same dose (2.5 ml of a 10 mg/ml formulation) results in a statistically significantly higher maximum serum level of parent fluphenazine. A tendency toward faster time to peak level was observed with the 10 mg/ml formulation but the difference was not statistically significant. Both of these differences are considered too small to be clinically significant. In a subgroup of 10 patients, pre-injection serum fluphenazine levels correlated significantly (Pearson r = 0.78, p < 0.05) with serum prolactin levels. PMID- 1457389 TI - Repetitive behaviors in chronically institutionalized schizophrenic patients. AB - Repetitive dysfunctional behaviors (e.g., polydipsia, bulimia, hoarding, mannerisms) are frequently observed in chronically institutionalized schizophrenics, cause significant morbidity and are readily reproduced in animal models. The goal of this study was to assess the frequency and severity of these behaviors. Thirty-two chronic schizophrenics on an extended treatment unit were rated on the Elgin Behavioral Rating Scale, which includes eight repetitive behaviors and eight positive and negative symptoms. Forty-seven percent of the patients exhibited at least one severe, or 2 moderate, repetitive behaviors, while 63% exhibited at least one severe or 2 moderate positive or negative symptoms. The mean total score (+/- SD) on the eight repetitive behaviors (10.3 +/- 6.1) was about 2/3 that for the eight positive and negative symptoms (15.3 +/ 8.9, t = 4.1, p = .0001). Interrater reliability for the repetitive behaviors was similar to that for the positive and negative symptoms. Repetitive behaviors were positively related to male gender, white race and total length of hospitalization. Repetitive dysfunctional behaviors are frequently observed and can be reliably rated in chronically institutionalized schizophrenics. PMID- 1457390 TI - Natural killer cell activity in schizophrenia and schizoaffective disorder: a pilot study. AB - Natural killer cell activity was prospectively studied in 15 patients with chronic schizophrenia and in seven patients with schizoaffective disorder, depressed type. These patients were compared to individually matched normal controls. No mean differences in natural killer cell activity between the patient groups and their controls were observed. PMID- 1457391 TI - Deficits in social schemata in schizophrenia. AB - Several recent studies have examined the manner in which social information is processed in an attempt to better understand the interpersonal functioning deficits of schizophrenia. In this study, the manner in which schizophrenic subjects represent social information, and the relationships between these social representations and measures of information processing, are examined. Specifically, 30 DSM-IIIR patients with schizophrenia and 15 normal controls were assessed on measures of social schema processing, information processing, and symptomatology. Results showed that schizophrenic patients earned significantly lower schema processing scores than the normal comparison group. Schema deficits of the schizophrenic group were significantly associated with recall memory and vigilance. These findings suggest that deficits in the representation of social information provides a unique perspective for understanding the interpersonal dysfunctions of schizophrenia. PMID- 1457392 TI - Selecting controls for schizophrenia research studies: the use of the National Adult Reading Test (NART) is a measure of premorbid ability. AB - The National Adult Reading Test (NART) has achieved popularity as a measure of pre-morbid intellectual ability, based on the premises that pronunciation of irregular words is unaffected in many clinical disorders and that performance is highly correlated with general intellectual ability. Recently, schizophrenia research studies have begun to appear in the literature, where the NART has been used to estimate pre-morbid ability. However, this use has preceded the basic required demonstration that, in fact, NART performance is unaffected by the schizophrenic process. In the present study, NART performance was compared across three groups; 20 acutely ill unmedicated DSM-IIIR schizophrenics, 10 other unmedicated acute psychotics, and 20 control subjects. When demographic variability between the groups was controlled for, there were no group differences in terms of NART performance. NART performance was not correlated with Brief Psychiatric Rating Scale scores, and in all three groups, no significant differences emerged when demographically predicted intelligence quotients were compared with NART estimated intelligence quotients. NART performance (predicted on the basis of demographic variables) was not significantly different from observed NART performance in any of the three experimental groups. However, within the sample with schizophrenia, NART estimated pre-morbid IQ was significantly higher than currently measured intellectual abilities. These results suggest that the National Adult Reading Test provides a reasonable estimate of pre-morbid ability in acutely ill, unmedicated schizophrenic patients. PMID- 1457393 TI - Positive and negative symptoms in the psychoses: multidimensional scaling of SAPS and SANS items. AB - Recently, the validity of the simple dichotomy between positive and negative symptoms in psychosis has been questioned. A newly admitted group of 114 DSM-III patients with psychotic disorder were assessed using Andreason's positive and negative symptoms scales. Multidimensional scaling, augmented by cluster analysis, was applied to the full item set of these scales and showed clearly that there are three major, independent groups of symptoms: Hallucinations/Delusions, Positive Thought Disorder and Negative Symptoms. Within the Hallucinations/Delusions and Negative Symptoms groups there was some additional structure which does not conform to the SAPS and SANS sub-scales. In particular there was considerable heterogeneity within the Hallucinations/Delusions group, and delusions of persecution may represent a fourth independent dimension of psychopathology which is under-represented in these scales. PMID- 1457394 TI - Procedural learning of cognitive and motor skills in psychotic patients. AB - Two kinds of procedural learning, viz. learning of a sequence of simple motor responses and learning to solve a rather complex problem (Tower of Hanoi), as well as declarative learning (word list learning) were investigated in a group of psychotic inpatients (n = 67) and a control group of non-psychotic psychiatric inpatients (n = 19). Within the psychotic group, correlations of the task variables with positive and negative symptoms were explored. There was no difference between both groups in motor procedural learning. Psychotic patients were less efficient than controls in solving the Tower problem, but both groups again showed an equal amount of procedural learning. Consistent with the literature, however, a clear difference between both groups was found in declarative learning. The memory tasks did not correlate significantly with psychotic symptoms. These findings are interpreted as another indication that automatic information processing in psychotic patients is intact. The results are discussed with reference to neuropsychological research on procedural learning in neurological patients. PMID- 1457395 TI - Semantic priming of word pronunciation and lexical decision in schizophrenia. AB - Experimental assessments of semantic memory structure and function in schizophrenic subjects can be a useful approach for delineating some of the information processing deficits in schizophrenia. In this study, a pronunciation and a lexical decision semantic priming experiment were conducted with 19 schizophrenic subjects and 20 normal controls. A short stimulus-onset asynchrony (250 msec) and a relatively low proportion of related prime-target pairs were used in order to examine automatic priming and in order to avoid the contribution of attentional, controlled processes. On the pronunciation task, schizophrenic subjects showed a significant priming effect, equal to the priming shown by normal controls. However, on the lexical decision task, schizophrenics, unlike normal controls, did not show a priming effect which is significantly greater than zero, even though the group difference in priming effect (interaction of priming effect by group) was nonsignificant. The lack of priming on the lexical decision task is consistent with the hypothesis that schizophrenic subjects may show abnormalities in the realm of post-lexical, controlled information processing. The equal-to-normal priming for schizophrenic subjects indicates that the basic structure of the semantic network, including associations among related concepts, is intact in schizophrenia, and that spreading activation also occurs normally. PMID- 1457396 TI - Carboxy-terminal-extended variant of the human fibrinogen alpha subunit: a novel exon conferring marked homology to beta and gamma subunits. AB - Similarities between the N-terminal regions of the three subunits of the clotting protein fibrinogen--(alpha beta gamma)2--suggest that they evolved from a common progenitor. However, to date no human alpha chain has been found with the strong C-terminal homology shared by the beta and gamma chains. Here we examine the natural product of a novel fibrinogen alpha chain transcript bearing a separate open reading frame that supplies the missing C-terminal homology to the other chains. Additional splicing leads to the use of this extra sequence as a sixth exon elongating the alpha chain by 35%. Since the extended alpha chain (alpha E) is assembled into fibrinogen molecules and its synthesis is enhanced by interleukin-6, it suggests participation in both the acute phase response and normal physiology. PMID- 1457397 TI - Helical structure and orientation of melittin in dispersed phospholipid membranes from amide exchange analysis in situ. AB - A trapping method combined with high-resolution nuclear magnetic resonance spectroscopy is described for the measurement of hydrogen-deuterium exchange rates for individual amides of polypeptides bound to fully hydrated, dispersed phospholipid bilayers. Exchange rates were measured for 22 of the 24 amide hydrogens of bee venom melittin bound to bilayers composed of egg phosphatidylcholine/phosphatidylserine (88:12, mol/mol) dispersed in 20 mM sodium acetate, pH 4.0. Amides of residues 5-11 and 16-22 had exchange rates suppressed by between 30- and 1000-fold, and the rate suppression exhibited a helical periodicity with amides on the hydrophobic helix face up to 20-fold more stable than those on the hydrophilic face of the helix. These results demonstrate that under the conditions studied melittin adopts a helical conformation with stable helical hydrogen bonds extending to residue 22 and that the helix is oriented with the hydrophobic face directed toward the membrane interior. PMID- 1457398 TI - Structure and dynamics of transmembrane signaling by the Escherichia coli aspartate receptor. AB - The structure of the cytosolic extension of the first transmembrane region (TM1) of the Escherichia coli aspartate receptor (residues 3, 4, and 5) and conformational changes within that region have been characterized by targeted cross-linking studies and by measurement of the effect of aspartate binding on cross-linking and methylation rates and compared with the periplasmic extension of the same helix. These experiments show that (1) the cytosolic extension of TM1 is helical, with residues 4 and 4' closest together at the dimer interface; (2) the helix is more solvent-exposed at the cytosolic side of the membrane than on the periplasmic side; and (3) aspartate binding enhances the rate of cross linking at Cys 4, and the resulting cross-linked receptor displays aspartate induced transmembrane increases in methylation by the cytoplasmic methylase (the CheR protein). We conclude that aspartate induces a conformational change that does not involve large intersubunit movements that lead to an increase in distance between the cytosolic ends of the first membrane-spanning helices; rather, the motion involved is largely contained within individual subunits, possibly resulting in a small movement between positions 4 and 4'. PMID- 1457399 TI - Structure-function analysis of Escherichia coli translation initiation factor IF3: tyrosine 107 and lysine 110 are required for ribosome binding. AB - Translation initiation factor IF3 is required for peptide chain initiation in Escherichia coli. IF3 binds directly to 30S ribosomal subunits ensuring a constant supply of free 30S subunits for initiation complex formation, participates in the kinetic selection of the correct initiator region of mRNA, and destabilizes initiation complexes containing noninitiator tRNAs. The roles that tyrosine 107 and lysine 110 play in IF3 function were examined by site directed mutagenesis. Tyrosine 107 was changed to either phenylalanine (Y107F) or leucine (Y107L), and lysine 110 was converted to either arginine (K110R) or leucine (K110L). These single amino acid changes resulted in a reduced affinity of IF3 for 30S subunits. Association equilibrium constants (M-1) for 30S subunit binding were as follows: wild-type, 7.8 x 10(7); Y107F, 4.1 x 10(7); Y107L, 1 x 10(7); K110R, 5.1 x 10(6); K110L, < 1 x 10(2). The mutant IF3s were similarly impaired in their abilities to specifically select initiation complexes containing tRNA(fMet). Toeprint analysis indicated that 5-fold more Y107L or K110R protein was required for proper initiator tRNA selection. K110L protein was unable to mediate this selection even at concentrations up to 10-fold higher than wild type. The results indicate that tyrosine 107 and lysine 110 are critical components of the ribosome binding domain of IF3 and, furthermore, that dissociation of complexes containing noninitiator tRNAs requires prior binding of IF3 to the ribosomes. PMID- 1457400 TI - Backbone dynamics of the glucocorticoid receptor DNA-binding domain. AB - The extent of rapid (picosecond) backbone motions within the glucocorticoid receptor DNA-binding domain (GR DBD) has been investigated using proton-detected heteronuclear NMR spectroscopy on uniformly 15N-labeled protein fragments containing the GR DBD. Sequence-specific 15N resonance assignments, based on two- and three-dimensional heteronuclear NMR spectra, are reported for 65 of 69 backbone amides within the segment C440-A509 of the rat GR in a protein fragment containing a total of 82 residues (MW = 9200). Individual backbone 15N spin lattice relaxation times (T1), rotating-frame spin-lattice relaxation times (T1 rho), and steady-state (1H)-15N nuclear Overhauser effects (NOEs) have been measured at 11.74 T for a majority of the backbone amide nitrogens within the segment C440-N506. T1 relaxation times and NOEs are interpreted in terms of a generalized order parameter (S2) and an effective correlation time (tau e) characterizing internal motions in each backbone amide using an optimized value for the correlation time for isotropic rotational motions of the protein (tau R = 6.3 ns). Average S2 order parameters are found to be similar (approximately 0.86 +/- 0.07) for various functional domains of the DBD. Qualitative inspection as well as quantitative analysis of the relaxation and NOE data suggests that the picosecond flexibility of the DBD backbone is limited and uniform over the entire protein, with the possible exception of residues S448-H451 of the first zinc domain and a few residues for which relaxation and NOE parameters were not obtained. in particular, we find no evidence for extensive rapid backbone motions within the second zinc domain. Our results therefore suggest that the second zinc domain is not disordered in the uncomplexed state of DBD, although the possibility of slowly exchanging (ordered) conformational states cannot be excluded in the present analysis. PMID- 1457401 TI - Cloning, nucleotide sequence, and chromosome localization of the human pleiotrophin gene. AB - Pleiotrophin (PTN), midkine (MK), and retinoic acid-induced heparin-binding (RI HB) protein are members of a recently discovered family of developmentally regulated cytokines. We report here the cloning, sequencing, chromosomal localization, and structural organization of the genomic version of the human PTN gene and its comparison to the mouse MK gene. The PTN gene was found to be arranged in five exons and four introns, in a fashion similar to that of the mouse MK gene. Exon 1, as for MK, does not appear to encode amino acid sequence. As in the case of the MK gene, exon 2 encodes the hydrophobic leader sequence of PTN, which constitutes the beginning of gene translation. The signal peptide cleavage site of both genes lies toward the 3' end of exon 2. Exons 3 and 4 of PTN were most closely related to exons 3 and 4 of the MK gene; in particular, six of the ten cysteine residues were coded for in exon 3 and the remaining 4 in exon 4. The intron-exon splice junctions of both genes occurred through the same residues. The two genes were found to be less closely related in the fifth exon which encodes the highly basic C-terminal domains, the translation termination codon, and the polyadenylation signal of both cDNAs. We also report approximately 2000 bp of the 5' untranslated sequence of the PTN gene and the site of initiation of transcription in human placenta. PTN was localized to human chromosome 7q33-34 by fluorescence in situ hybridization. These data confirm the existence of a new gene family of developmentally regulated cytokines. PMID- 1457402 TI - Comparative circular dichroism studies of an anti-fluorescein monoclonal antibody (Mab 4-4-20) and its derivatives. AB - This study presents circular dichroism (CD) spectra of a high-affinity monoclonal anti-fluorescein antibody (Mab 4-4-20), its Fab fragments, and corresponding single-chain antibody (SCA). In the region 200-250 nm, the differences in the CD spectra between these proteins reflect the uneven distribution of chromophores (tryptophan and tyrosine) rather than a major conformational change. On the basis of near-UV CD spectra, binding of the hapten fluorescein to these protein antibodies elicits an increased asymmetry in the microenvironment of the chromophoric residues in contact with the hapten and also perturbs the interface between VL and VH domains. The hapten-binding site provides a chiral microenvironment for fluorescein that elicits a pronounced induced fluorescein CD spectrum in both the visible and UV regions. In contrast to the parent molecules, SCA is thermolabile. Our results demonstrate that (1) UV CD spectra are useful for assessing the chromophoric microenvironment in the binding portion of antibodies and (2) the extrinsic fluorescein hapten CD spectra provide information about the interaction of hapten with the binding pocket. PMID- 1457403 TI - Characterization of recombinant HIV-1 Tat and its interaction with TAR RNA. AB - Recombinant HIV-1 Tat (Tat 1-86) has been purified from the cytoplasmic fraction of Escherichia coli without the use of protein denaturants or chaotropic agents. Chloroquine-mediated uptake of the purified protein into cells resulted in transactivation of the HIV LTR promoter. Tat retains 1.64 mol of Zn2+/mol of protein by atomic absorption spectroscopy. Circular dichroism measurements indicated that the structure of recombinant Tat contains 15-20% alpha-helix. Filter binding assays showed that Tat binds to a 63-nucleotide target TAR RNA with a dissociation constant (Kd) of 10 nM at 25 degrees C, 0.05 M ionic strength, pH 7.5, in a 1:1 Tat-TAR RNA stoichiometry. Nonelectrostatic interactions provide the principal source of free energy of association. While the pH optimum occurs over a wide H+ concentration, the salt dependence of Kd indicates formation of a single ion pair. UV-induced protein-RNA cross-linking produced a labeled Tat-TAR RNA adduct, indicating that direct contact occurred between the Tat protein and TAR RNA. PMID- 1457404 TI - DNA sequence selectivities in the covalent bonding of antibiotic saframycins Mx1, Mx3, A, and S deduced from MPE.Fe(II) footprinting and exonuclease III stop assays. AB - DNA sequence selectivities in the covalent binding of the antitumor antibiotic saframycins Mx1, Mx3, A, and S have been determined by complementary strand MPE.Fe(II) footprinting and exonuclease III stop assays on two different 545 and 135 base pair long HindIII/RsaI restriction fragments of pBR322 DNA. Saframycins Mx1, Mx3, A, and S recognize primarily 5'-GGG sequences. All four antibiotics also recognize 5'-GGPy sequences, however a cytosine is preferred over a thymine at the 3'-end of this recognition site in all cases. Saframycins Mx1, Mx3 and S, which possess the OH leaving group, also recognize the 5'-CCG sequence, in contrast to saframycin A, which contains the CN leaving group. In contrast, the OH-containing saframycins also recognize the 5'-CTA sequence. Saframycins Mx2, B and C, which lack the critical CN or OH leaving group, do not show any footprints on the restriction fragments examined in this study. The measured binding site size for all four antibiotics is three base pairs. The exonuclease III stop assay independently confirmed the formation of a covalent bond and the strong preference of the antibiotics for 5'-GGG and 5'-GCC sequences. The latter enzyme assay also suggests that the 5'-terminal or central G of the triad binding site is the base to which reversible covalent attachment of the antibiotic takes place. PMID- 1457405 TI - Very stable mismatch duplexes: structural and thermodynamic studies on tandem G.A mismatches in DNA. AB - We have used ultraviolet melting techniques to compare the stability of several DNA duplexes containing tandem G.A mismatches to similar duplexes containing tandem A.G, I.A, and T.A base pairs. We have found that tandem G.A mismatches in 5'-Y-G-A-R-3' duplexes are more stable than their I.A counterparts and that they are sometimes more stable than tandem 5'-Y-T-A-R-3' sequences. This is not the case for tandem G.A mismatches in other base stacking environments, and it suggests that tandem G.A mismatches in 5'-Y-G-A-R-3' sequences have a unique configuration. In contrast to tandem 5'-G-A-3' mismatches, tandem 5'-A-G-3' mismatches were found to be unstable in all cases examined. PMID- 1457406 TI - Influence of an exocyclic guanine adduct on the thermal stability, conformation, and melting thermodynamics of a DNA duplex. AB - As part of an overall program to characterize the impact of mutagenic lesions on the physiochemical properties of DNA, we report here the results of a comparative spectroscopic study on pairs of DNA duplexes both with and without an exocyclic guanine lesion. Specifically, we have studied a family of four 13-mer duplexes of the form d(CGCATGYGTACGC).d(GCGTACZCATGCG) in which Y is either the normal deoxyguanosine residue (G) or the exocyclic guanine adduct 1,N2 propanodeoxyguanosine (X), while Z is either deoxycytosine (C) or deoxyadenosine (A). Thus, the four duplexes studied, which can be designated by the identity of their central Y.Z base pair, are a Watson-Crick duplex (GC), a duplex with a central mismatch (GA), and two duplexes with exocyclic guanine lesions (X), that differ only by the base opposite the lesion (XC and XA). The data derived from our spectroscopic measurements on these four duplexes have allowed us to evaluate the influence of the exocyclic guanine lesion, as well as the base opposite the lesion, on the conformation, thermal stability, and melting energetics of the host DNA duplex. To be specific, our circular dichroism (CD) spectra show that the exocyclic guanine lesion induces alterations in the duplex structure, while our temperature-dependent optical measurements reveal that these lesion-induced structural alterations reduce the thermal stability, the transition enthalpy, and the transition free energy of the duplex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457407 TI - Solution structure of the TnAn DNA duplex GCCGTTAACGCG containing the HpaI restriction site. AB - The solution structure of the self-complementary DNA duplex [d(GCCGTTAACGGC)]2, which contains the HpaI restriction site GTTAAC, has been elucidated by two dimensional NMR, distance geometry (DG), and NOE back-calculation methods. Initial distance constraints were determined by polynomial fitting the two-spin initial NOE rates; backbone constraints from NOE and J-coupling observations (Kim et al., 1992) were included. RMSDs between initial-distance-refined structures derived from random-embedded DG, A-DNA, and B-DNA starting structures were all in the range 0.5-1.0 A, indicating good convergence properties of the algorithm, regardless of the starting structure. A semiautomatic back-calculation refinement procedure was developed and used to generate more refined structures for which the BKCALC-simulated NOE volumes matched the experimental data. The six final structures refined from various starting structures exhibit very good agreement with the experimental data (R values = 0.18) and converge well to within 0.8-A RMSD differences for the central 8 base pairs. The torsion and pseudorotation phase angles were found to be well determined by the data, and the local helical parameters for each base step converged quite well. The final structures show that the central T6-A7 step is somewhat underwound (twist angle ca. 29 degrees), with a large negative cup and a normal (wide) minor groove width, while the T5-T6 and A7-A8 steps have a partially narrowed minor groove. PMID- 1457408 TI - Site-directed analysis of the functional domains in the factor Xa inhibitor tick anticoagulant peptide: identification of two distinct regions that constitute the enzyme recognition sites. AB - Recombinant tick anticoagulant peptide (rTAP) is a highly selective inhibitor of blood coagulation factor Xa. rTAP has been characterized kinetically as a slow, tight-binding, competitive inhibitor of the enzyme. We used an approach consisting of both recombinant, site-directed mutagenesis and solid-phase chemical synthesis to generate 31 independent mutations in rTAP to identify those regions of the molecule which contribute to the specific, high-affinity binding interaction with factor Xa. Our results demonstrate that the four amino-terminal residues of rTAP constitute the primary recognition determinant necessary for the formation of the high-affinity enzyme-inhibitor complex. The Arg residue in position three is probably not interacting with the S1-specificity pocket of factor Xa in a substrate-like manner since substitution at this position with a D Arg amino acid produced only a modest decrease in affinity (5-fold). An additional domain in the rTAP molecule located between residues 40 and 54 was identified as a probable secondary binding determinant. Interestingly, this region in rTAP shares significant amino acid sequence homology with a sequence in prothrombin immediately amino-terminal to the factor Xa cleavage site that generates meizothrombin. These observations indicate that specific segments within two different regions of the rTAP molecule contribute to the potent binding interaction between rTAP and factor Xa. PMID- 1457409 TI - Expression of platelet-derived endothelial cell growth factor in Escherichia coli and confirmation of its thymidine phosphorylase activity. AB - Platelet-derived endothelial cell growth factor (PD-ECGF) has been expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The fusion protein was purified by one-step affinity chromatography on glutathione agarose beads, and recombinant PD-ECGF was proteolytically cleaved with thrombin from its GST leader peptide to yield pure protein. Recombinant PD-ECGF stimulated [3H]methylthymidine uptake by endothelial cells in vitro; however, we were unable to detect stimulation of cell proliferation under a wide variety of conditions. We confirm that in accord with the recent report that PD-ECGF and human thymidine phosphorylase are products of the same gene [Furukawa, T., Yoshimura, A., Sumizawa, T., Haraguchi, M., & Akiyama, S. I. (1992) Nature 356, 668] recombinant PD-ECGF has thymidine phosphorylase activity comparable to that of E. coli thymidine phosphorylase. Further, E. coli thymidine phosphorylase was able to mimic the activity of recombinant PD-ECGF in the [3H]methylthymidine uptake assay, and it appears that recombinant PD-ECGF's effect on the uptake of thymidine by endothelial cells may be due to modulation of cellular thymidine pools. The mechanism by which PD-ECGF stimulates angiogenesis remains to be elucidated. PMID- 1457411 TI - Orotidylate decarboxylase: insights into the catalytic mechanism from substrate specificity studies. AB - Pyrimidine nucleotides were tested as substrates for pure yeast orotidylate decarboxylase in an attempt to gain insight into the nature of the catalytic mechanism of the enzyme. Substitutions of the 5-position in the pyrimidine ring of the orotidylate substrate resulted in compounds that are either excellent inhibitors or substrates of the enzyme. The 5-bromo- and 5-chloroorotidylates are potent inhibitors while the 5-fluoro derivative is a good substrate with a turnover number 30 times that observed with orotidylate. When carbon 5 of the pyrimidine ring is replaced by nitrogen in 5-azaorotidylate, the resulting compound is unstable in solution with a half-life of 25 min at pH 6. However, studies with freshly generated 5-azaorotidylate show that an enzyme-dependent reaction occurs, presumably decarboxylation. This enzyme reaction follows simple Michaelis-Menten kinetics. Because the 5-aza group is not electrophilic, an enzyme mechanism utilizing a nucleophilic addition of the enzyme at the 5 position is ruled out. We also present studies that are not compatible with a mechanism requiring the formation of a Schiff's base prior to decarboxylation. The enzyme is tolerant of modest substitution at the 4-position, for the 4-keto group can be replaced with a thioketone. However, no catalysis is observed when the same substitution is made at the 2-position. Similarities in the substrate specificity of orotate phosphoribosyltransferase and orotidylate decarboxylase led us to compare the amino acid sequences of the two enzymes; significant (20%) sequence homology was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457410 TI - Identification of topaquinone and its consensus sequence in copper amine oxidases. AB - The nature of the active site cofactor and the amino acid sequence flanking this structure have been determined in a range of copper amine oxidases. For enzymes from porcine plasma, porcine kidney, and pea seedlings, proteolytic digestion was performed on phenylhydrazone or p-nitrophenylhydrazone derivatives. Thermolysin treatment leads to relatively small active site peptides, which have been characterized by Edman degradation and by resonance Raman spectroscopy. Resonance Raman spectra of peptides show identical peak positions and intensities relative to each other and to a model p-nitrophenylhydrazone derivative of topaquinone hydantoin, establishing topaquinone as the cofactor in each instance. Edman degradation of peptides provides active site sequences for comparison to previous determinations with bovine serum and yeast amine oxidases. The available data establish a consensus sequence of Asn, Topa, Asp/Glu. Trypsin leads to significantly longer peptides, which reveal a high degree of sequence identity between plasma proteins from bovine and porcine sources (89%), with significantly decreased identity between the porcine serum and intracellular amine oxidases (56%). A lower degree of identity (45%) is observed between the pea seedling and mammalian enzymes. As an alternative to the isolation of active site peptides for topaquinone identification, visible spectra of intact proteins have been investigated. It is shown that p-nitrophenylhydrazone derivatives of native enzymes, active site-derived peptides, and a topaquinone model exhibit identical behavior, absorbing at 457-463 nm at neutral pH (pH 7.2) and at 575-587 nm in basic solution (1-2 M KOH). These spectral properties, which appear unique to topaquinone, provide a rapid and simple test for the presence of this cofactor in intact enzymes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457412 TI - A unique catalytic and inhibitor-binding role for Lys93 of yeast orotidylate decarboxylase. AB - The presence of a proton-donating catalytic amino acid side chain in orotidylate decarboxylase (ODCase) was sought by site-directed mutagenesis. Replacement of yeast ODCase Lys93 with a cysteine resulted in a mutant protein (K93C) with no measurable activity, representing a decrease in activity by a factor of, at most, 2 x 10(-8) times the activity of the wild-type enzyme. Treatment of this mutant protein with 2-bromoethylamine, designed to append Cys93 to yield S-(2 aminoethyl)cysteine, restored activity by a factor of at least 5 x 10(5) over the untreated mutant protein. Activity could not be restored by treatment with other brominated reagents designed to replace the epsilon-amino of S-(2 aminoethyl)Cys93 with a different functional group. The overall architecture of the K93C protein was not significantly changed, as judged by the similar dimerization properties (in the absence of ligands) of the mutant enzyme compared to the wild-type enzyme. The binding affinity of the substrate orotidylate was not measurably changed by the mutation, indicating that Lys93 has an essential role in catalysis which is mechanistically distinguishable from substrate binding. Apparently the mutation removes an integral portion of the active site and does not drastically affect the structural or substrate binding properties. However, the affinities of the mutant protein for the competitive inhibitors 6 azauridylate (6-azaUMP) and UMP are significantly altered from the pattern seen with the wild-type enzyme. The K93C protein has an affinity for the neutral ligand UMP which is greater than that for the anionic 6-azaUMP, in clear contrast to the preference for 6-azaUMP displayed by the wild-type enzyme. Lys93 is apparently critical for catalysis of the substrate to product and for the binding of anionic inhibitors; the data are discussed in terms of previously existing models for transition-state analogue inhibitor binding and catalysis. PMID- 1457413 TI - Characterization by infrared spectroscopy of the interaction of a cardiotoxin with phosphatidic acid and with binary mixtures of phosphatidic acid and phosphatidylcholine. AB - The effect of cardiotoxin IIa from Naja mossambica mossambica, a small basic protein extracted from snake venom, on dimyristoylphosphatidic acid (DMPA) and on equimolar mixtures of DMPA and dimyristoylphosphatidylcholine (DMPC) has been studied by Fourier transform infrared spectroscopy. The interaction of cardiotoxin with DMPA dispersions decreases both the cooperativity of the phase transition of the lipid and the molecular order of the lipid acyl chains in the gel phase. This effect increases with the proportion of the toxin in the complexes and leads to the total abolition of the phase transition of DMPA at a lipid-to-protein molar ratio of 5. Small-angle X-ray results demonstrate that the structure of the lipid-protein complexes is poorly ordered and gives rise to broad diffusion peaks rather than to well-resolved diffraction patterns. Infrared spectra of oriented cardiotoxin-DMPA films show that the protein is not homogeneously oriented with respect to the bilayer surface. The destabilization of the gel-phase structure of DMPA by cardiotoxin also results in a deeper water penetration in the interfacial region of the lipid since more carbonyl ester groups appear to be hydrogen bonded in the presence of the toxin. The infrared results on the phosphate group vibrations also indicate clearly that the basic residues of cardiotoxin interact strongly with the phosphate group of DMPA that becomes partly ionized at a pH as low as 6.5. The results obtained on the interaction of cardiotoxin with an equimolar mixture of DMPA and DMPC clearly demonstrate the ability of this toxin to induce lateral phase separation in this mixture with one phase containing DMPA-rich domains perturbed by cardiotoxin while the second phase is composed of regions enriched in DMPC. Comparison of the results of the current study with those obtained on other basic proteins and polypeptides suggests that charge-induced phase separation occurs only when the charge density on certain regions of the protein structure is high enough to lead to efficient electrostatic interactions with anionic phospholipids. This condition occurs only when the conformation of the protein or polypeptide is well ordered at the lipid interface. PMID- 1457414 TI - The major glycolipid recognized by SP-D in surfactant is phosphatidylinositol. AB - Surfactant protein D (SP-D), a multimeric calcium-dependent lectin isolated from pulmonary alveolar lavage, has been previously shown to interact reversibly with crude surfactant [Persson et al. (1990) J. Biol. Chem. 265, 5755-5760]. In this study, SP-D is shown to interact reversibly with a preparation of organelles enriched in lamellar bodies, in a manner inhibited by calcium-chelating agents and by competing saccharides. An interaction with an endogenous glycoprotein could not be identified by electrophoresis of surfactant or lamellar body associated proteins followed by electrotransfer of the separated proteins to nitrocellulose and then probing with radioiodinated SP-D via lectin overlay. Separation of the surfactant or lamellar body lipids on two-dimensional thin layer chromatography (2D-TLC) followed by probing with radioiodinated SP-D via lectin overlay demonstrated binding to a single lipid. This interaction was dependent on the presence of calcium and was inhibited by competing saccharides. By assaying column fractions for the ability to bind radioiodinated SP-D after TLC, the glycolipid was purified to homogeneity and identified as phosphatidylinositol (PI). Identification was confirmed by mass spectrometry. We further demonstrate the ability of radiolabeled SP-D to bind to PI presented in a lipid bilayer through separation of free SP-D from liposome-bound SP-D on density gradients of Percoll. The interaction of SP-D with PI is dependent on calcium and inhibited by competing saccharides. SP-D binds with similar efficiency to liposomes with mole fractions of PI ranging from 2.5% to 30%, thereby demonstrating the lectin's ability to recognize mole fractions of PI available in surfactant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457415 TI - Gangliosides: differentiation markers for murine T helper lymphocyte subpopulations TH1 and TH2. AB - On the basis of the pattern of lymphokines they secrete, murine T helper clones can be divided into two subsets, TH1 and TH2. This concept of two different T helper effector cells helps to explain the diversity of immune reactions occurring in different parts of the body. The in vivo localization of T helper subtypes is of great interest, but up to now no biochemical or surface markers were available to distinguish between them. We analyzed the glycolipids from altogether 12 murine TH1 and TH2 cell lines or clones. A comparison of the gangliosides by thin-layer chromatography showed differences between the TH1 and TH2 cells. Binding studies with specific antibodies to asialo backbone structures after degradation by neuraminidases showed that the main gangliosides from these lymphocytes shared a common GgOse4 backbone and thus differed only in their degree or position of sialylation. Two disialogangliosides appeared to be characteristic. They were isolated from the D10.G4.1 TH2 cell clone and identified by fast atom bombardment mass spectrometry as IVNeuAc,IINeuAc GgOse4Cer (GD1a) and IVNeuAc,IIINeuAc-GgOse4Cer (GD1 alpha), respectively. GD1a was characteristically only detected in TH2 cells, whereas GD1 alpha was preferably, but not exclusively, expressed by TH1 lymphocytes. Although GD1a was also found in the lung, heart, kidney, and spleen, its expression within the murine immune cells under investigation was unique to TH2 lymphocytes. Scarcely any GD1a was found in thymocytes, B cells, or CD8 positive (cytolytic) T cells, but significant expression was seen in CD4 positive (helper) T cells which include the TH2 subpopulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457416 TI - Structure of the N- and O-glycans of the A-chain of human plasma alpha 2HS glycoprotein as deduced from the chemical compositions of the derivatives prepared by stepwise degradation with exoglycosidases. AB - The structure of the glycans of the A-chain of human plasma alpha 2HS glycoprotein was established from the chemical compositions of its derivatives prepared by sequential enzymatic degradation of the carbohydrate moiety, from the determination of the kind and amount of the monosaccharides liberated after each step of the enzymatic digestion, and from the distinct specificity of the highly purified exoglycosidases. The exoglycosidases were three sialidases (Vibrio cholerae, fowl plague virus, and Arthrobacter ureafaciens), two beta galactosidases (Streptococcus pneumoniae and bovine testis), one alpha-N acetylgalactosaminidase, one beta-N-acetylglucosaminidase, and one alpha mannosidase. Utilizing sialidases with different cleavage specificities, the number of alpha 2-3- and alpha 2-6-linked sialic acid residues could be separately determined. As to the beta-galactosidases, the enzyme isolated from S. pneumoniae cleaves only beta 1-4-linked galactose residues, whereas the bovine testes enzyme acts on both the beta 1-4- and beta 1-3-linked galactose residues. Jack bean beta-N-acetylglucosaminidase cleaves beta 1-2, beta 1-4, and beta 1-6 GlcNAc with higher activity for the beta 1-2. Jack bean alpha-mannosidase cleaves alpha 1-2, alpha 1-6, and alpha 1-3 Man with greater activity for alpha 1-2 and alpha 1-6. Bovine liver alpha-N-acetylgalactosaminidase cleaves O-linked GalNAc. On the basis of these results, the A-chain of alpha 2 HS-glycoprotein was found to possess two biantennary N-glycans and two O-linked trisaccharides. PMID- 1457417 TI - The oxygen-evolving complex requires chloride to prevent hydrogen peroxide formation. AB - Illumination of PSII core preparations can cause the production of H2O2 at rates which approach 60 mumol of H2O2 (mg of Chl.h)-1. The rate of peroxide production is maximal at pH 7.2 at low sucrose concentrations and at concentrations of Cl- (1.5-3.0 mM) that limit the rate of the oxidation of water to O2. The rate of H2O2 production increased with pH from pH 6.8 to 7.2 and was inversely proportional to the oxidation of water to O2 from pH 6.8 to 7.5. While EDTA does not inhibit H2O2 production, this reaction is abolished by 5 mM NH2OH and inhibited by the same concentrations of NH3 that affect water oxidation which indicates that the oxygen-evolving complex is responsible for the production of peroxide generated upon illumination of PSII core preparations. These results support a mechanism in which bound Cl- in the S2 state is displaced by OH- ions which are then oxidized by the OEC to form H2O2. Thus, the OEC requires Cl- to prevent access to the active site of the OEC until four oxidizing equivalents can be generated to allow the oxidation of water to O2. PMID- 1457418 TI - Anomeric specificity of D-xylose isomerase. AB - Crystal structures of complexes of D-xylose isomerase with deoxysugars have been determined. Deoxynojirimycin is a structural analogue of alpha-pyranose and mimics the binding of these aldose substrates. The structure of this complex supports the hypothesis that an imidazole group catalyzes ring opening of the pyranose. The steric restrictions in the active site of the enzyme prevent a beta pyranose from binding in the same way. For the reverse reaction with ketoses, the anomeric specificity is less certain. Dideoxyimino-D-glucitol is a structural analogue of the ketose alpha-D-furanose. The binding of the inhibitor dideoxyimino-D-glucitol to the crystals of the enzyme does not mimic the binding of the reactive alpha-D-fructofuranose. Superposition of the nonphysiological substrate alpha-D-fructofuranose onto the atomic positions of dideoxyimino-D glucitol is not possible due to the steric restrictions of the active site. However, by utilizing the approximate 2-fold symmetry of the sugar, a stereochemically sensible model is produced which is consistent with other data. In addition to reaction with alpha-D-furanose, the enzyme probably reacts with open ring keto sugars which are present at significant concentrations. Other sugars which resemble furanoses either do not inhibit significantly or are not observed in the crystals bound in a single conformation. PMID- 1457419 TI - Molecular movements in the actomyosin complex: F-actin-promoted internal cross linking of the 25- and 20-kDa heavy chain fragments of skeletal myosin subfragment. AB - We describe, for the first time, the F-actin-promoted changes in the spatial relationship of strands in the NH2-terminal 25-kDa and COOH-terminal 20-kDa heavy chain fragments of the skeletal myosin subfragment 1 (S-1), detected by their exclusive chemical cross-linking in the rigor F-actin-S-1 complex with m maleimidobenzoic acid N-hydroxysuccinimide ester (MBS). Quantitative electrophoretic analysis of the reaction products showed extensive conversion of the 95-kDa heavy chain of the actin-bound S-1 into a new species with an apparent mass of 135 kDa (yield = 50-60%), whereas the heavy chain mobility remained unaffected when actin was omitted. The 135-kDa entity retained the fluorescence of AEDANS-S-1 but not of AEDANS-actin, indicating that it was not a cross-linked acto-heavy chain adduct. Its extent of production depended markedly on the S-1: actin molar ratio and was maximum near a ratio of 1:4. The MBS treatment of acto S-1 led also to some covalent actin-actin oligomers which could be suppressed by using trypsin-truncated F-actin lacking Cys-374, without altering the generation of the 135-kDa heavy chain derivative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457420 TI - Effect of 2,3-butanedione monoxime on myosin and myofibrillar ATPases. An example of an uncompetitive inhibitor. AB - 2,3-Butanedione monoxime (BDM) reversibly inhibits force production in muscle. At least part of its action appears to be directly on the contractile apparatus. To understand better its mechanism of action, we studied the effect of BDM on the steps of myosin subfragment 1 Mg(2+)-ATPase in 0.1 M potassium acetate, pH 7.4. Because of the rapidity of certain processes, we experimented at 4 degrees C and our main technique was the rapid flow quench method. By varying the experimental conditions (relative concentrations of reagents, time scale, quenching agent), it was possible to study selectively the different steps of the S1 Mg(2+)-ATPase: [formula: see text] At saturation (20 mM), BDM had two major effects on the ATPase. First, it increased the equilibrium constant of the cleavage step (K3) from 2 to > 10. Second, it slowed the kinetics of the release of Pi by an order of magnitude (k4; from 0.054 to 0.004 s-1). By contrast, the kinetics of the binding of ATP (k) and the release of ADP (k6) were little affected by BDM. Thus, the oxime appears to interact specifically with M**.ADP.Pi, and it is a rare example of an uncompetitive inhibitor. Its effect is to reduce the steady-state concentration of the "strong" actin binding state M*.ADP and to increase that of the "weak" binding state, M**.ADP.Pi. The effect of BDM on the initial ATPase of Ca2+ activated myofibrils was very similar to that on S1 ATPase. Thus, with myofibrils too BDM seems to exert its main effect subsequent to the initial binding and cleavage steps.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457421 TI - Conformation of tachyplesin I from Tachypleus tridentatus when interacting with lipid matrices. AB - The mode of action of tachyplesin I, an antimicrobial cationic heptadecapeptide amide isolated from the hemocyte debris of a horseshoe crab, Tachypleus tridentatus, toward lipid matrices was studied with synthetic tachyplesin I, its analogs with Phe in place of Trp or Tyr, a linear analog with no disulfide bonds, and two linear short fragments. Circular dichroism spectra showed that tachyplesin I took an antiparallel beta-structure in buffer solution and a certain less ordered structure in acidic liposomes composed of egg phosphatidylcholine and egg phosphatidylglycerol (3:1). Spectrophotometric titration of the peptides with laurylphosphorylcholine revealed that both Trp and Tyr residues orient toward the inside of lipid matrices, suggesting that they are on the same side of the peptide backbone. The carboxyfluorescein leakage experiment and fluorescence data indicated that tachyplesin I interacted strongly with neutral and acidic lipid bilayers and an aromaticity-rich hydrophobic part of the peptide was embedded in lipid membranes. All the peptides except for the short fragments were almost equally active in lipopolysaccharide binding. The energy-transfer experiment showed that a conformational change occurred such that the Tyr and Trp residues are positioned more closely to each other in acidic liposomes than in buffer solution. The present study strongly suggested that amphipathic lipid bilayers induced a conformational change of tachyplesin I from an energetically stable beta-structure to a less ordered, probably more amphipathic structure. PMID- 1457422 TI - Molten globule monomer to condensed dimer: role of disulfide bonds in platelet factor-4 folding and subunit association. AB - Platelet factor 4 (PF4) exhibits high affinity for heparin and exists as a tetramer in solution under physiologic conditions. Reduction of the two disulfide bridges in PF4 increases the protein's dissociation constant for heparin approximately 20-fold and shifts the highest apparent aggregation state from tetramer to dimer as evidenced by gel filtration, chemical cross-linking, and 1H NMR studies. 1H-NMR spectra of reduced PF4 monomers generally show narrower, less dispersed, upfield-shifted NH and alpha H resonances, suggesting the presence of an unfolded monomer state. Reduced PF4 monomer folding, however, is evidenced by the presence of about 12 relatively long-lived backbone NHs and by CD spectra that indicate conservation of overall secondary structure. These data suggest the presence of a molten globule-type state. Urea denaturation shifts this apparent molten globule to a fully unfolded state characterized by more random coil-like resonance shifts. The reduced PF4 dimer state yields NMR and CD data consistent with preservation of tertiary structural folds found for the native species. In this regard, the reduced PF4 folding transition is thermodynamically linked with dimer formation which stabilizes tertiary structure. Monomer-dimer association equilibria for reduced PF4 essentially follow the same pH and salt titration trends as reported previously for native PF4 dimers [Mayo, K. H., & Chen, M. J. (1989) Biochemistry 28, 9469-9478], indicating that that dimer interface is generally conserved in the absence of disulfide constraints. Reduced PF4 tetramers are not apparent under any conditions investigated, suggesting that disulfides are necessary for efficient antiparallel beta-sheet alignment between dimer pairs. PMID- 1457423 TI - Structure of the proteolytic fragment F34 of calmodulin in the absence and presence of mastoparan as revealed by solution X-ray scattering. AB - The solution X-ray scattering technique has been applied to examine the conformations of the proteolytic fragment F34 (78Asp-148Lys) of calmodulin in the absence of both Ca2+ and mastoparan, in the presence of Ca2+ only, and in the presence of both Ca2+ and mastoparan. The radius of gyration and the molecular weight for the F34 fragment increased by 1.1 +/- 0.3 A and 19%, respectively, upon binding of both 2 mol of Ca2+/mol to the F34 fragment and mastoparan to form the tertiary complex. A smaller change was found for the Ca(2+)-saturated F34 fragment in the absence of mastoparan (0.3 +/- 0.3 A) without any change of the molecular weight. The analysis based on the small-angle scattering data showed that the F34 fragment in the presence of Ca2+ alone preserved the tertiary structure of the globular domain in the crystal to a great extent. Further analyses based on a two-domain model showed that the center-to-center distance between F34 and mastoparan is about 12.7 A, if the structure of the F34 fragment in the presence of mastoparan resembles that in the absence of mastoparan and if mastoparan in the complex retains an alpha-helical conformation. The modeling studies using their crystal structure coordinates have been made on the basis of the solution X-ray scattering data. The combined results support a model proposed by Persechini and Kretsinger [Persechini, A., & Kretsinger, R. H. (1988) J. Cardiovasc. Pharmacol. 12 (Suppl. 5), S1-S12], although the center-to-center distance between mastoparan and the F34 fragment is shorter by about 5 A than that in their model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457424 TI - Trimerization of the heat shock transcription factor by a triple-stranded alpha helical coiled-coil. AB - We have isolated and characterized a 91 amino acid fragment of the heat shock transcription factor from both Saccharomyces cerevisiae and Kluyveromyces lactis. The two protein fragments behave similarly: they form homotrimers, as indicated by sedimentation equilibrium and cross-linking, and contain approximately 80% alpha-helix, as indicated by circular dichroism. Sedimentation velocity and diffusion coefficients indicate that they have an elongated, nonspherical shape. We conclude the following: these fragments contain a domain which forms a trimer via a triple-stranded alpha-helical coiled-coil, similar to that found in influenza hemagglutinin. PMID- 1457425 TI - Interleukin-6, a marker of preservation injury in clinical lung transplantation. AB - Interleukin-6 (IL-6) is one of the cytokines produced by human alveolar macrophages, lung parenchyma, and other cells in response to injury and infection. We hypothesized that IL-6 is released from poorly preserved lung grafts and may serve as a marker of preservation injury. Sixteen patients who received lung allografts were enrolled in this study. The average ischemic time was 284 +/- 78 minutes. Serum IL-6 level was measured before and at 4 and 24 hours after reperfusion of the grafts by an enzyme-linked immunosorbent assay. Preservation injury was assessed by (1) the need for prolonged intubation (> 7 days), (2) the arterial/alveolar oxygen tension ratio (PaO2/PAO2 ratio) at 4 hours after graft reperfusion (only in heart-lung or double lung recipients), (3) the presence of diffuse alveolar damage on first lung biopsy, and (4) the 30-day graft survival rate. IL-6 level peaked at 4 hours after reperfusion and returned to baseline at 24 hours. The patients were divided into group I (n = 6) and group II (n = 10), depending on whether the 4-hour IL-6 level was more than 1000 pg/ml or less than 500 pg/ml, respectively. Group I patients required longer intubation (p < 0.01) and had a lower PaO2/PAO2 ratio (p < 0.001), more diffuse alveolar damage (p < 0.01), and a lower graft survival rate (p < 0.01) than those of group II. No bacterial, fungal, or viral infection was found during postoperative week 1 in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457426 TI - Effects of allopurinol pretreatment with pulmonary flush on lung preservation. AB - This study was designed to test whether use of allopurinol could improve lung preservation after 6 hours of cold storage. Thirty-two rabbits were divided into four groups (n = 8 each group): (1) the control group received no flush or storage, (2) the EC group received Euro-Collins (EC) solution for both flush and storage, (3) the Allo-F group received Euro-Collins solution with allopurinol (1 mmol/L) for both flush and storage, and (4) the Allo-R group received Euro Collins solution to which allopurinol (1 mmol/L) was added only to the reperfused blood. For groups 2 through 4, the lungs were flushed (40 ml/kg) in situ, excised, and then stored at 4 degrees C. After storage, the lungs were reperfused for 1 hour with an in vitro blood-perfused ventilated model. Lung function was measured during reperfusion with mean pulmonary arterial pressure, end inspiratory airway pressure, and blood gas data. The lung wet/dry weight ratio was used to measure lung edema. The lungs in the EC group had a significant increase in mean pulmonary arterial pressure, airway pressure, and wet/dry weight ratio when compared with the control group. The mean pulmonary arterial pressure in either of the groups receiving allopurinol was consistently lower than that in the EC group. The airway pressure in the Allo-R group also significantly decreased compared with the EC group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457427 TI - Graft cytokine mRNA activity in rat single lung transplants by reverse transcription-polymerase chain reaction: effect of cyclosporine. AB - Intragraft levels of cytokine mRNA were studied in an orthotopic rat left lung transplant model. Three groups of rats were compared at 7 days after transplantation. Isogeneic (Lewis to Lewis), allogeneic (Brown-Norway to Lewis) untreated, and cyclosporine-treated (25 mg/kg/day, intramuscularly) allogeneic animals underwent analysis of cytokine mRNA isolated from total RNA in freshly excised grafts. Reverse transcription-polymerase chain reaction amplification of interleukin (IL)-2, IL-4, and actin (control) mRNA was performed with custom synthesized oligonucleotide amplimers targeted to known sequences of rat IL-2 and IL-4 cDNA. Semiquantitative analysis was performed by radioanalytic scanning of gel preparations. Sample specimens from the retrieved grafts were also graded histologically for rejection on a five-point scale. Rejection was most severe in the untreated allografts (p < 0.003). IL-2 mRNA was significantly greater in the untreated allografts when compared with isografts (p < 0.05) and cyclosporine treated allografts (p < 0.05). No significant differences in IL-4 mRNA between groups were observed. We conclude that semiquantitative analysis of cytokine mRNA by reverse transcription-polymerase chain reaction is a useful and sensitive method for the study of acute rejection in lung grafts and that this technique may become an important tool in future studies of cytokine-mediated responses in cyclosporine-treated allografts. PMID- 1457428 TI - Changes in serum catecholamine levels in patients who are brain dead. AB - Prospective blood samplings from 15 patients admitted with a Glasgow Coma Score of less than 7 were obtained to observe and compare epinephrine, norepinephrine, and dopamine serum levels in patients with brain injury before, after, and in the absence of brain death. Nine of the patients developed or were admitted after brain death. Wide variations in catecholamine blood levels over time were documented, and subgroup analysis precluded useful statistical comparison or inference of the data. The data are presented therefore as descriptive observations only. No apparent differences were noted between similarly injured patients in whom brain death did not develop and patients before brain death or between patients with penetrating versus nonpenetrating brain injury. Brain death was preceded by hypertension and corresponding elevations in serum catecholamine levels in one patient with complete data. Catecholamine levels appeared to fall after brain death in most patients. Only minimal changes in myocardial histology were present in three donor hearts, and the two transplanted hearts functioned satisfactorily. Serum catecholamine measurement or monitoring does not provide a precise method of determining potential injury to the donor heart before or after brain death. Other experimental data and clinical observation indicate that some hearts may be injured in the donor during the evolution of brain death. Pharmacologic intervention may prevent such injury in experimental animals but must be used before brain death is induced. Such interventions should be studied in selected human donors before brain death to determine whether cardiac function is improved in the donor or recipient. PMID- 1457429 TI - Remnant atrial function in human and animal recipients of a total artificial heart. AB - The native atria remains intact after total artificial heart (TAH) implantation. The electrical activity of the recipient's atria can be recorded from wires placed during TAH implantation. Regulating TAH heart rate by coupling it with native atrial activity has the potential for a more physiologically responsive TAH. The reactivity of the atrial impulse rate is a critical component of this link, but little is known about atrial responsiveness after TAH placement. Two human and three animal TAH recipients had recordable atrial electrical activity. Human atrial impulse rate after TAH was relatively constant at rest but unresponsive to physiologic stimuli. Analysis of human atrial contraction provided no discernable effect on ventricular filling. Animal atrial impulse rate at rest was more rapid than calves without a TAH. The bovine TAH recipients had an atrial impulse rate that responded to catecholamine stimulation and blockade. Isoproterenol caused a significant rise in atrial impulse rate (152 +/- 16 impulses per minute to 216 +/- 24 impulses per minute; p < 0.05) and propranolol caused a decrease in atrial impulse rate (142 +/- 20 impulses per minute to 122 +/- 19 impulses per minute; p > 0.05). Despite beta blockade, the atrial impulse rate remained abnormally elevated secondary to unknown factors. Animal atrial contraction did appear to intermittently augment TAH ventricular filling. These data indicate that the atria remains electrically intact after TAH implantation. The human atrial impulse rate was unresponsive to physiologic stimuli although the animal atrial impulse rate was affected by exogenous catecholamine administration, but the rate remained abnormally rapid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457431 TI - Sinoatrial node dysfunction in recipients of domino heart transplants: complication of a surgical harvesting technique. AB - Two of six domino transplantations performed at our institution required permanent pacemaker implantation as a result of persistent sinoatrial node dysfunction and symptomatic nodal rhythm. Retrospective analysis of several potential etiologic factors showed that the only obvious difference between these two patients and the remaining four domino transplant recipients without this complication was the technique used during harvesting of the cardiac graft. The hearts from the two patients with sinoatrial node dysfunction were harvested using a "right atrial cuff preservation" technique, and the hearts of the remaining four patients were harvested with a standard bicaval division technique. Based on this experience, we think that this right atrial cuff preservation harvesting technique carries a potential risk for sinoatrial node damage, and we do not recommend its use for domino transplantation. PMID- 1457430 TI - Early diagnosis and follow-up by echocardiography of acquired cor triatriatum after orthotopic heart transplantation. AB - Acquired cor triatriatum in a heart transplant recipient, secondary to a prominent left atrial suture line and torsion of the atria, was diagnosed immediately after cardiopulmonary bypass by transesophageal echocardiography. The patient was followed with serial echocardiograms and right heart catheterizations, showing resolution of the obstruction. PMID- 1457432 TI - Leukocyte-depleted reperfusion of transplanted human hearts: a randomized, double blind clinical trial. AB - Standard methods of myocardial preservation for heart transplantation have generally provided good results. Preservation times beyond 3 hours, however, have been associated with decreased survival. Leukocyte-mediated reperfusion injury is partly responsible for decreased graft function after prolonged graft ischemia. Leukocyte-depleted reperfusion has been shown experimentally to improve cardiac function after cold ischemic arrest. To determine the efficacy and safety of leukocyte-depleted reperfusion, 20 patients were enrolled in a randomized, double blind clinical trial to be treated with either warm whole blood reperfusion (group I; n = 9) or warm leukocyte-depleted blood reperfusion (group II; n = 11). Reperfusion with leukocyte-depleted blood or whole blood was carried out for 10 minutes, with enriched cardioplegic solution added for the first 3 minutes of reperfusion. The mean donor and recipient age and the ischemic time (142 versus 153 minutes) were not significantly different between the two groups. Coronary sinus release of creatinine phosphokinase-MB 5 minutes after reperfusion was significantly less in group II (1.65 EU/min) than in group I (3.83 units/min; p = 0.05). Thromboxane B2 release was also significantly less (p = 0.05) in group II (33.6 pg/min) than in group I (67.0 pg/min). All hearts functioned adequately in both groups. The duration of inotropic support was shorter in group II than in group I, but the difference was not statistically significant. Postoperative hemodynamics, rejection episodes, and infectious complications were also not significantly different between groups in a mean follow-up of 9 months. Mean ejection fraction 1 month after operation was 65% in both groups. One early death occurred at 66 days secondary to infection; two late deaths occurred in group II, both from rejection. Leukocyte-depleted reperfusion is safe and easily applied in the operating room. Furthermore, leukocyte-depleted reperfusion decreases biochemical evidence of reperfusion injury. Although not influencing postoperative cardiac function when the ischemic time is short, less than 3 hours, leukocyte-depleted reperfusion may prevent significant reperfusion injury and improve posttransplantation graft function when ischemic times are long. Safe extension of the ischemic time would expand the donor pool and allow for better crossmatching. PMID- 1457433 TI - Clinical heart transplantation without routine endomyocardial biopsy. AB - In a prospective clinical study, routine endomyocardial biopsy (EMB) for early detection of cardiac allograft rejection was replaced by two noninvasive diagnostic techniques. In 32 patients who underwent transplantation during a 6 month period, intramyocardial electrogram (IMEG) amplitude was recorded with the telemetry function of a dual-chamber pacemaker system. An amplitude decrease of more than 8% below the individual range of variability in overnight long-term recordings served as an indicator of rejection. A prolongation of the time interval Te--the time span between maximal posterior wall contraction and peak retraction velocity--of more than 20 msec was used as an additional indicator of rejection-related left ventricular dysfunction. For patient safety, routine EMBs were still performed but remained undisclosed to the transplantation team. The pathologist was asked to intervene in cases of discrepancies between biopsy results and medical decisions, but no such intervention was necessary. Twenty seven rejection episodes were treated medically, of which 22 were diagnosed noninvasively. In four patients, EMB, ordered because noninvasive parameters remained inconclusive, led to medical treatment. No false negative IMEG results were observed. Retrospective correlation with rejection gave a 100% negative predictive value for IMEG and a 96.9% negative predictive value for echocardiographic diagnosis. We conclude that omission of a schedule of routine biopsies is justified, if the described techniques of IMEG and echocardiography are meticulously applied and indicate normal cardiac function. EMB remains indicated if noninvasive parameters are not conclusive or if false-positive IMEG results, which were observed in the presence of infection or arrhythmias, are suspected. The frequency of EMB can be reduced by 90%, compared to conventional routine biopsy schedules. Diagnostic safety is increased because the additional information gained from IMEG and echocardiography is helpful in the interpretation of EMBs. PMID- 1457434 TI - Methotrexate pulse therapy in the treatment of recurrent acute heart rejection. AB - Despite cytolytic induction therapy and triple-drug immunosuppression, acute allograft rejection continues to cause important morbidity and occasional death after heart transplantation. Between November 1, 1988, and May 1, 1990, 24 patients received methotrexate pulse therapy for recurrent or persistent acute rejection despite methylprednisolone, OKT3, or antithymocyte globulin therapy. Methotrexate was administered as a daily oral dose of 2.5 to 15 mg on 1 day/week over 3 weeks (longer in 15 patients because of either severe leukopenia with temporary interruption of therapy or recurrent rejection during methotrexate therapy) with reduction or discontinuation of azathioprine. Rejection incidence was reduced from 1.1 episodes/patient month before methotrexate therapy to 0.2 episodes/patient month after completion of therapy (p = 0.0001). Two patients died within 3 months after treatment, one of cytomegalovirus pneumonia and one of lymphoma. Mean white blood count (WBC) fell from 6900 per ml before methotrexate therapy to 3700 during the first month of methotrexate therapy (p = 0.0005). The lowest WBC typically occurred about 3 weeks after starting methotrexate therapy, and a transient WBC of less than 1000/ml developed in seven patients. By multivariable analysis, the WBC 1 month after starting methotrexate therapy was significantly related to greater bone marrow suppression (lower WBC), immediately before methotrexate therapy, greater overall immunosuppression (more rejection episodes) during the 3 months before methotrexate therapy, and a higher total dose of methotrexate. The following conclusions can be drawn: (1) Methotrexate is a useful adjunct in the treatment of recurrent or persistent rejection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457435 TI - Acute septal myocardial infarction diagnosed by endomyocardial biopsy in a heart transplant recipient. AB - We describe an unusual case of acute septal myocardial infarction in a heart transplant recipient. The clinical presentation was most suggestive of acute rejection; the correct diagnosis was first made by endomyocardial biopsy and was then verified by coronary angiography. Acute myocardial infarction should be included in the differential diagnosis of acute rejection after heart transplantation and included among the possible diagnoses made by endomyocardial biopsy in these patients. PMID- 1457436 TI - Cyclosporine interactions with miconazole and other azole-antimycotics: a case report and review of the literature. AB - Several antimicrobial drugs have been shown to pharmacokinetically interact with cyclosporine. On two separate occasions, we observed increases in cyclosporine plasma concentrations during concomitant miconazole therapy in a heart transplant patient with an infection secondary to Pseudallescheria boydii. To our knowledge, no interaction between cyclosporine and miconazole has previously been reported. In addition, drug interactions were observed between cyclosporine and ketoconazole and possibly between cyclosporine and SCH 39304, an investigational azole-antifungal agent. No interaction was noted between cyclosporine and fluconazole. In general, clinicians should anticipate drug interactions between cyclosporine and azole-antimycotic agents. PMID- 1457437 TI - Efficacy of dobutamine in the failing transplanted heart. AB - Acute rejection often leads to severe myocardial failure and death. Surprisingly, no systematic study on the efficacy of beta-adrenergic pharmacologic agents have been reported to the present. Because of all the pathophysiologic alterations documented during rejection, we expected an inappropriate response to inotropic drugs, so we have questioned the value of dobutamine during those circumstances. Twelve dogs underwent orthotopic transplantation and were prepared with implantable devices for serial hemodynamic studies to be performed on the resting unanesthetized subject. Of this number, six dogs were studied while they were in immediate postoperative heart failure (3 hours after operation), and the same study was performed when myocardial failure secondary to rejection occurred (5 to 7 days). After basal state measurement, 5 and 10 micrograms.kg-1.min-1 of dobutamine were infused continuously, and the hemodynamic response during the two phases was compared. The baseline cardiac index in the immediate postoperative period was 1.4 +/- 0.4 L.min-1.m2 and 1.8 +/- 1.0 L.min-1.m2 during rejection, showing a similar degree of heart failure. Dobutamine (5 micrograms.kg-1.min-1) increased cardiac index by 97% 3 hours after transplantation and by 35% during rejection (p < 0.05). With 10 micrograms.kg-1.min-1 of dobutamine, the difference between increments was not significant (99% versus 79%). Raising the infusion rate of the drug to 15 and 20 micrograms.kg-1.min-1 during rejection increased cardiac index by 97% and 118%, respectively. Interestingly, no detrimental tachycardia occurred with this increased dosage. Heart failure secondary to acute rejection can therefore be improved by dobutamine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457438 TI - Hemodynamic performance in a heterotopically transplanted dog heart: proposal of techniques for working left heart model of heterotopic (abdominal) heart transplantation. AB - To study hemodynamics together with various aspects of rejection after experimental heart transplantation, we developed a technique to produce a working left heart model of heterotopic (abdominal) heart transplantation. The interatrial septum and tricuspid valve of the donor heart are removed. The pulmonary arterial trunk, pulmonary veins, and inferior vena cava are ligated, and the stumps of the donor aorta and superior vena cava are anastomosed in an end-to-side fashion to the recipient abdominal aorta and inferior vena cava, respectively. Arterial blood from the recipient abdominal aorta thus perfuses the donor myocardium through the coronary artery, and the donor left ventricle receives venous blood from the recipient inferior vena cava as preload. In this model, the donor left ventricle does not pump out enough venous blood to desaturate the recipient femoral arterial blood but does generate approximately the same pressure as the recipient's heart. This model is reproducible, easy to manage, and can be applied to heterotopic heart transplantation in various experimental animals including rats. PMID- 1457439 TI - Living with a donor heart: feelings and attitudes of patients toward the donor and the donor organ. AB - For the patient, heart transplantation means more than an operation; adjustment to its rigors requires a high degree of personal strength and adequacy of coping skills. The goal of our study was to gain insight into how heart transplant patients cope with the fact that their own heart has been replaced by a donor organ from an unknown dead donor who was the target of disease, accident, or even suicide. Over a period of 2 years 44 transplant patients were interviewed after rehabilitation in a semi-structured interview regarding their feelings about and reactions to the graft and the donor. Their answers were recorded, transcribed, and analyzed as to content. Three groups of patients were identified: (1) the complete deniers (N = 15), who denied thinking about the donor; (2) the partial deniers (N = 17), who were aware of avoiding thinking about the donor; and those who coped (N = 12), who accepted the death of the donor as reality and also reported having more or less close connections with the donor. Eighty-two percent of the patients interviewed accepted the donor heart immediately as their own, whereas the remaining 18% avoided talking and thinking about the graft and donor. The findings are supported by verbatim statements of patients. The role of defense mechanisms in heart transplant patients is discussed. PMID- 1457440 TI - Natural history and predictors of obesity after orthotopic heart transplantation. AB - Excessive weight gain resulting in obesity is commonly seen after orthotopic heart transplantation. Obesity increases the risk for the development of many significant health problems and the associated morbidity and mortality. The purpose of this study was to define the occurrence, magnitude, and predictors of overweight/obesity in this group. We followed 47 consecutive patients for 1 year after orthotopic heart transplantation for changes in weight. Weight gain from baseline was significant at months 2, 4, 6, 8, and 10, with significant weight increments between each measurement interval (p < 0.05). The mean weight gain was 10.1 kg +/- 1.6 (standard error [SE]) at 12 months. Based on entry body mass index patients were divided into two groups: group I, overweight/obese, body mass index more than 27 kg/m2 (n = 11); group II, not overweight/obese, body mass index 27 kg/m2 or less (n = 36). No significant difference was found in the amount of weight gained between the two groups (group I, 10.3 kg +/- 1.2 [SE]; group II, 10.1 kg +/- 1.4 [SE]). Only age predicted weight gain, with younger patients gaining more than older patients after transplantation (14.2 +/- 13.2 kg versus 8.8 +/- 7.9 kg; p < 0.05). We found no relationship between the observed weight gain and any of the other measured predictors, that is, history of overweight, age, diabetes, family history of overweight, sex, patient's participation in cardiac rehabilitation. The universal nature of this weight gain and the lack of markers predicting patients at greatest risk for obesity underscores the seriousness of this problem. PMID- 1457441 TI - The psychosocial impact of pediatric heart transplantation. AB - Children with terminal heart disease experience a dramatic improvement in functional status after heart transplantation but may be at increased risk for problems in psychosocial adaptation. Selected psychosocial outcomes were assessed in 49 pediatric heart transplant recipients and their families from five heart transplantation centers. Heart transplant recipients did not appear significantly different from their peers on self-report measures of self-concept and anxiety, but they showed significantly less social competence and more behavior problems than a normative population. Behavior problems observed were most frequently suggestive of depression and were significantly associated with greater family stress and diminished family resources for managing stress. The study findings further suggest that the heart transplant recipients' ability to verbalize or ventilate their feelings and concerns to others seems to facilitate psychosocial adaptation. Assessment of stress, resources, and coping is imperative to enable health professionals to promote the psychosocial adaptation of pediatric heart transplant recipients and their families. PMID- 1457442 TI - Relationship of cardiac allograft size and pulmonary vascular resistance to long term cardiopulmonary function. AB - The purpose of this study was to evaluate the long-term cardiopulmonary function of heart transplant patients who received disproportionately sized allografts for varying levels of pulmonary vascular resistance. Resting hemodynamics and oxygen uptake during exercise were recorded at 1 year after transplantation in 52 patients. No differences in resting heart rate, cardiac output, stroke volume, peak oxygen uptake during exercise, and exercise duration were found in recipients of undersized hearts (donor:recipient weight ratio [D:R] < 0.75), sized-matched hearts (D:R = 0.75 to 1.25), and oversized (D:R > 1.25) hearts. In a further analysis according to preoperative pulmonary vascular resistance, resting cardiac output (5.8 +/- 1.3 L/min) was normal, and peak exercise oxygen uptake (22.7 +/- 8.0 ml/kg/min) was mildly decreased in recipients of size matched allografts with a pulmonary vascular resistance of less than 3 Wood units (size-matched hearts, with mild or no pulmonary vascular resistance). Of patients with moderate pulmonary hypertension (pulmonary vascular resistance > or = 3 Wood units), resting cardiac output was normal (5.1 +/- 0.6 L/min) in recipients of oversized hearts and was reduced (4.7 +/- 1.0 L/min) in recipients of sized matched hearts (p < 0.05 versus recipients of size-matched hearts with pulmonary vascular resistance less than 3 Wood units).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457443 TI - Clinical results of heart transplantation in recipients over 55 years of age with donors over 40 years of age. AB - Between November 1985 and November 1991, 180 patients underwent heart transplantation at our institution; 55 of these patients (31%) were over 55 years of age. Eighteen patients (10%) received hearts from donors who were over 40 years of age (mean age, 47 years; range, 40 to 55 years); (group 1); 37 hearts (21%) were from donors who were under 40 years of age (mean age, 23 years; range, 8 to 38 years). Mean recipient age was 59 years (range, 55 to 64 years) and 57 years (range, 55 to 68 years) in groups 1 and 2, respectively. The main indication for transplantation was ischemic heart disease in group 1 and dilated cardiomyopathy in group 2. Perioperative mortality and intensive care assistance were similar in the two groups. Survival was 88% versus 84% at 1 year and 81% versus 80% at 4 years in groups 1 and 2, respectively. Although infections were more frequent in group 1 (0.27 versus 0.11 episode/patient), the incidence of acute rejection was comparable in the two groups (1.50 versus 1.65 episode/patient). Angiographic and echocardiographic controls showed normal graft function up to 4 years, with low incidence of chronic rejection in both groups. We conclude that heart transplantation in patients over 55 years of age with donors over 40 years of age offers excellent short-term and mid-term results. The consideration of older donors makes heart transplantation a valid therapeutic option for selected patients in the sixth and seventh decade of life, in spite of chronic donor shortage. PMID- 1457444 TI - Adult heart transplantation: adverse role of chronic alcoholism in donors on early graft function. AB - Because of the increasing shortage of heart donors, selection criteria have been gradually extended. The purpose of this study was to determine the donor-related factors implied in early graft dysfunction and to define new selection criteria. The 70 consecutive adult patients who underwent heart transplantation in our institution between January 1988 and February 1992 were retrospectively studied. Mean donor age was 38 +/- 11 years (10 donors were more than 50 years of age; two donors were more than 60 years of age). Mean ischemic time was 130 +/- 39 minutes. An important proportion of donors (20%) had a history of chronic alcoholism. Thirteen patients experienced immediate graft dysfunction; five of them died within the first operative month. The different parameters studied, which were found to have no significant influence on the early graft function, were the age of the donor, the duration of inotropic support and the dose administered, a relative hemodynamic instability, resuscitation maneuvers, chest trauma, and weight mismatch between donor and recipient. Ischemic time was significantly longer in patients who died of cardiac dysfunction (p < 0.05). Chronic alcoholism in the donor was a very detrimental factor: 54% of patients who had early graft dysfunction versus only 12% of patients who had immediate normal graft function had received a graft from an alcoholic donor (p = 0.003). Excluding such alcoholic donors or reserving them for critically-ill recipients, with an increased risk of early graft dysfunction would be preferable. PMID- 1457445 TI - Effect of estradiol on accelerated atherosclerosis in rabbit heterotopic aortic allografts. AB - Migration and proliferation of vascular smooth muscle cells are early and major events in the formation of atherosclerotic lesions. We report on an aorta transplant model in rabbits wherein myointimal proliferation is inhibited by 17 beta-estradiol. The abdominal aortas of outbred white New Zealand rabbits were harvested and allografted to the carotid artery of the recipient. The animals, which were fed either a normal or a high-cholesterol (0.5%) diet, were killed 3 weeks later. The degree of myointimal proliferation was measured with a digitized system attached to a light microscope. The myointimal hyperplasia was expressed as the cross section area of the intima/the area of the intima + the area of the media x 100. Transmission electron micrographs were obtained for all vessels. Intimal thickening was shown mainly to consist of proliferating smooth muscle cells. The cholesterol diet resulted in significantly higher serum total cholesterol levels compared to animals on a normal diet (p < 0.0001) but did not affect serum high-density lipoprotein-cholesterol or serum triglyceride levels. The cholesterol diet was also associated with a greater but not significant amount of intimal thickening. Treatment with 17-beta-estradiol significantly decreased both serum triglyceride concentration (p < 0.05) and myointimal thickening (p < 0.01) in cholesterol-fed animals. Transmission electron microscopy showed that the endothelial cells appeared structurally normal in the estradiol-treated animals. Further, estradiol prevented the appearance of vacuolized macrophages. Thus estradiol may decrease myointimal thickening by preserving the endothelium and preventing macrophage appearance in the intima.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457446 TI - Effect of calcium channel antagonists on renal function in hypertensive heart transplant recipients. AB - Orthotopic heart transplant recipients treated with immunosuppressive regimens based on cyclosporine have a high incidence of hypertension. Cyclosporine-induced nephrotoxicity characterized by afferent glomerular arteriolar vasoconstriction also develops in these patients. Calcium channel antagonists produce afferent glomerular arteriolar vasodilation. Angiotensin-converting enzyme inhibitors (ACEI) dilate the efferent arteriole and have been suggested to decrease glomerular filtration rate in subjects taking cyclosporine. To test the hypothesis that calcium channel antagonists would improve glomerular filtration rate in heart transplant patients receiving ACEI treatment, we reviewed the charts of our patients whose treatment for hypertension had been changed from an ACEI to a calcium channel antagonist. A change in renal function was assessed by the average of serum creatinine level, blood urea nitrogen, and creatinine clearance within 3 months before and after the change from ACEI to calcium channel antagonist. Blood pressure was assessed on two different occasions before and after conversion to calcium channel antagonist. The data were analyzed by a paired Student t test. Serum blood urea nitrogen and creatinine levels decreased significantly when patients were treated with calcium channel antagonists (p < 0.05). Creatinine clearance increased in all patients when the treatment was converted to a calcium channel antagonist (CCA) (ACEI = 56.4 +/- 19.3 ml/min versus CCA = 71.06 +/- 23.77, N = 9; p < 0.005). A 5-mm Hg decrease occurred in mean arterial pressure when treatment was changed from ACEI to calcium channel antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457447 TI - Effects of double-filtration plasmapheresis and a platelet-activating factor antagonist on the prolongation of xenograft survival. AB - Xenotransplantation may be considered a possible solution to the clinical donor organ shortage. We studied the effects of the removal of preformed natural antibodies against donor tissue by double-filtration plasmapheresis (DFPP) and the administration of a platelet-activating factor antagonist on the prolongation of xenograft survival using the pig-to-dog model. The porcine hearts were perfused with the blood of mongrel dogs. Pairs of animals were divided into four groups: group I (n = 3) was given no pretreatment before perfusion; group II (n = 6) was pretreated by DFPP; group III (n = 3) was given a platelet-activating factor antagonist intravenously at a dose of 0.1 mg/kg 5 minutes before and after perfusion; group IV (n = 5) was pretreated by DFPP and then given a platelet activating factor antagonist. The titer of natural antibodies was measured by lymphocytotoxicity and hemagglutination. Heart specimens were examined by immunohistochemical staining for deposits of dog antibodies. No immunosuppressive drugs were given in this study. The porcine hearts resumed beating immediately after perfusion in all groups. The mean duration of the graft beating was 17.0 +/ 2.0 minutes for group I, 215.2 +/- 22.6 minutes for group II (p < 0.001 compared with group I), 18.3 +/- 2.1 minutes for group III, and 317.0 +/- 26.5 minutes for group IV (p < 0.001 compared with group II). Immunoglobulin (Ig) M, IgG, complements (C3, C4), and fibrinogen were removed significantly from the perfusing blood, and natural antibody titer was scarcely detectable in groups II and IV after DFPP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457448 TI - Evidence for antibody and immune-complex deposition in heart transplantation: a report of three cases. AB - Immunofluorescence microscopy of endomyocardial biopsy specimens from heart allograft recipients identified immunopathologic changes in three of 17 patients. These changes included immunoglobulin G and complement C3 deposition in tissue structures such as capillary endothelium and basal membranes, cardiomyocyte sarcolemma, and interstitial tissue. Moreover, the immunopathologic changes could be correlated with acute cellular rejection episodes evidenced by endomyocardial biopsy criteria. PMID- 1457449 TI - Henri Metras: a pioneer in lung transplantation. PMID- 1457450 TI - Cefaclor uptake by the proton-dependent dipeptide transport carrier of human intestinal Caco-2 cells and comparison to cephalexin uptake. AB - The human Caco-2 cell line spontaneously differentiates in culture to epithelial cells possessing intestinal enterocytic-like properties. These cells possess a proton-dependent dipeptide transport carrier that mediates the uptake of the cephalosporin antibiotic cephalexin (Dantzig, A.H. and Bergin, L. (1990) Biochim. Biophys. Acta 1027, 211-217). In the present study, the uptake of cefaclor was examined and found to be sodium-independent, proton-dependent, and energy dependent. The initial rate of D-[3-phenyl-3H]cefaclor uptake was measured over a wide concentration range; uptake was mediated by a single saturable transport carrier with a Km of 7.6 mM and a Vmax of 7.6 nmol/min per mg protein and by a non-saturable component. Uptake was inhibited by dipeptides but not amino acids. The carrier showed a preference for the L-isomer. The effect of the presence of a 5-fold excess of other beta-lactam antibiotics was examined on the initial rates of 1 mM cefaclor and 1 mM cephalexin uptake. Uptake rates were inhibited by the orally absorbed antibiotics, cefadroxil, cefaclor, loracarbef, and cephradine and less so by the parenteral agents tested. The initial uptake rates of both D-[9 14C]cephalexin and D-[3-phenyl-3H]cefaclor were competitively inhibited by cephalexin, cefaclor, and loracarbef with Ki values of 9.2-13.2, 10.7-6.2, and 7.7-6.4 mM, respectively. Taken together, these data suggest that a single proton dependent dipeptide transport carrier mediates the uptake of these orally absorbed antibiotics into Caco-2 cells, and provide further support for the use of Caco-2 cells as a cellular model for the study of the intestinal proton dependent dipeptide transporter. PMID- 1457451 TI - The conformational behaviour of phosphatidylinositol in model membranes: 2H-NMR studies. AB - Dimyristoylphosphatidylinositol (DMPI) has been synthesized with the appropriate natural stereochemistry and labelled with deuterium at specific sites in the D myo-inositol headgroup. 2H-NMR spectroscopy of DMPI in its lamellar phase at a molar ratio of water-to-lipid RW/L of 129 and at 70 degrees C reveals quadrupolar splittings delta v of 3.83 and 2.17 kHz, respectively, for the five axially oriented C-D bonds and the single equatorially oriented C-D bond of the D-myo inositol headgroup. Between RW/L ratios of 129 and 210 and between 30 degrees C and 80 degrees C the value of the ratio of these splittings delta nu ax/delta nu eq varies significantly (between 1.17 and 4.38). If it is assumed that, at a particular temperature, there is a single preferred orientation of the inositol headgroup, and that motion of the DPMI molecule establishes axial symmetry with respect to the bilayer normal then the ratio of these quadrupolar splittings can be used to impose constraints on that orientation. For example, the data are inconsistent with a situation in which the inositol ring lies parallel to the membrane surface and are difficult to reconcile with an arrangement where the inositol ring lies perpendicular to the surface. Computational modelling identifies four possible 'tilted' orientations, all of which are consistent with the data, and two of these allow good intramolecular hydrogen bonds to be formed. In one there is hydrogen bonding between the inositol C2-OH and the phosphate pro R oxygen. This is close to the conformation previously identified as being dominant in DMSO solution (Bushby, R.J., Byard, S.J., Hansbro, P.M. and Reid, D.G. (1990) Biochim. Biophys. Acta 1044, 231-236). PMID- 1457452 TI - Shear stress-facilitated calcium ion transport across lipid bilayers. AB - Small unilamellar liposomes were used in this study of shear stress effects on the trans-bilayer flux of calcium ions (Ca2+). Liposome suspensions were prepared from 99% egg phosphatidylcholine by a microporous filter extrusion technique. The inner aqueous phase of the unilamellar liposomes contained indo-1(5-), a fluorescent indicator of free Ca2+. The external aqueous phase was composed of Hepes-buffered saline containing normal physiological levels of common ionic species. Calcium ion levels were set at 100 nM and 1 mM in the inner and outer aqueous phases, respectively. Liposome suspensions were exposed to graded levels of uniform shear stress in an optically modified rotational viscometer. Intraliposome Ca2+ concentration was estimated from continuous measurement of indo-1(5-) fluorescence. Electronically measured particle size distribution was used to determine liposome surface area for estimation of trans-bilayer Ca2+ flux. Trans-bilayer Ca2+ flux increased linearly with applied shear rate from 27 s-1 to 2700 s-1. Diffusional resistance of the lipid bilayer, not the convective resistance of the surrounding fluid, was the limiting step in the transport of Ca2+. Liposome permeability to Ca2+ increased by nearly two orders of magnitude over the physiologically relevant shear rate range studied. Solute transport in injectable liposome preparations may be dramatically influenced by cardiovascular fluid stress. Solute delivery rates determined in liposomes exposed to static conditions may not accurately predict in vivo, cardiovascular solute transport. PMID- 1457453 TI - Isolation of the plasma membrane and organelles from Chinese hamster ovary cells. AB - Two methods are described enabling the plasma membrane from Chinese hamster ovary (CHO) cells to be obtained rapidly, relatively pure and with a good yield. In both cases, cells were disrupted by nitrogen cavitation in an isoosmotic buffer either at pH 5.4 or at pH 7.4. In the first approach, cells were lysed at pH 7.4 and the plasma membrane and cell organelles were isolated on a self-generated gradient of Percoll, at neutral pH. Mitochondria and endoplasmic reticulum were recovered in the denser fractions, plasma membrane fragments were found in the lighter fractions, but always contaminated by lysosomes. Because lysosomes were found to sediment in acidic conditions, cells were lysed at pH 5.4 and presedimentation (1500 x g) of the cell homogenate at the same pH enabled more than 80% of the lysosomes to be removed. Then, ultracentrifugation of the supernatant over a Percoll gradient at neutral pH yielded plasma membrane fractions practically free of lysosomes with an enrichment ratio of 3 and fractions of mitochondria and endoplasmic reticulum with enrichment ratios of 17 and 6, respectively. A major problem was encountered in the final step of elimination of Percoll from the purified plasma membrane fractions. Whatever the technique used for eliminating Percoll, plasma membranes were observed to be contaminated by a Percoll constituent which prevented further purification and biochemical identification of the lipids extracted from these membrane fractions to be carried out. A second method of plasma membrane preparation was tested consisting first in the coating of the cell surface with positive colloidal silica which was stabilized by an anionic polymer. Then, and through differential centrifugations, plasma membrane fractions were easily obtained within less than 1 h, with a yield of 65% and an enrichment ratio of 7. The coating pellicle was quantitatively removed thus enabling any biochemical manipulation of the plasma membrane to be carried out. The lipids present in the plasma membrane of CHO cells were analyzed and are described, both in terms of headgroup and acyl chain composition. PMID- 1457454 TI - Influence of retinoids on phosphatidylethanolamine lipid polymorphism. AB - The interaction of all-trans-retinoic acid and all-trans-retinol with dielaidoylphosphatidylethanolamine has been studied by differential scanning calorimetry and 31P-NMR spectroscopy. Increasing concentrations of all-trans retinoic acid up to a mol fraction of 0.09 were found to induce shifts to lower temperatures of both the L beta to L alpha and L alpha to hexagonal-HII phase transitions, with a slight decrease in the enthalpy change of the transitions. At higher concentrations no further effects on the transitions were observed, and this is interpreted as indicative of a limited miscibility of retinoic acid with the phospholipid. 31P-NMR spectroscopy confirmed that the L alpha to hexagonal HII phase transition was shifted to lower temperatures in the presence of retinoic acid. On the other hand increasing concentrations of all-trans-retinol up to a mol fraction of 0.166, induced a progressive shift of the L beta to L alpha and the L alpha to hexagonal-HII phase transitions to lower temperatures. At higher concentrations the main gel to liquid-crystalline phase transition was further displaced to lower temperatures and the lamellar to hexagonal-HII phase transition was not observed in the thermograms. 31P-NMR spectroscopy indicated that retinol was able of inducing the phospholipid to adopt the hexagonal-HII phase at temperatures even below the main gel to liquid-crystalline phase transition temperature of the pure phospholipid. PMID- 1457455 TI - Structure and activity studies of pardaxin and analogues using model membranes of phosphatidylcholine. AB - Thirteen synthetic pardaxin analogues were assayed for their ability to interact with model membranes of phosphatidylcholine. The results suggested the following: An amphipathic alpha-helix from isoleucine-14 to leucine-26 is responsible for most of the membrane perturbing properties of pardaxin. A hydrophobic N-terminal region enhances the activity of the isoleucine-14 to leucine-26 alpha-helix by binding the pardaxin molecule to the lipid bilayer. A bend centered around 12Ser 13Pro appears to create overall amphipathicity for the two different helical regions of pardaxin, but this contributes only slightly to potency. The C terminal amino acids are unimportant for membrane perturbing activity and may be present only to enhance transportation in an aqueous environment prior to membrane binding in the native system. PMID- 1457456 TI - Interaction of synthetic glycophospholipids with phospholipid bilayer membranes. AB - A series of glycophospholipids synthesized by coupling mono-, di-, or tri saccharides to dioleoylphosphatidylethanolamine (DOPE) by reductive amination was used to investigate the interaction of glycophospholipids with phospholipid bilayer membranes. These synthetic glycophospholipids functioned as a stabilizer for the formation of DOPE bilayer vesicles. The minimal mol% of glycophospholipid needed to stabilize the DOPE vesicles were as follows: 8% N-neuraminlactosyl-DOPE (NANL-DOPE), 20% N-maltotriosyl-DOPE (MAT-DOPE), 30% N-lactosyl-DOPE (Lac-DOPE), and 42% N-galactosyl-DOPE (Gal-DOPE). The estimated hydration number of glycophospholipid in reverse micelles was 87, 73, 46, and 14 for NANL-DOPE, MAT DOPE, Lac-DOPE, and Gal-DOPE, respectively. Thus, the hydration intensity of the glycophospholipid was directly related to the ability to stabilize the DOPE bilayer phase for vesicle formation. Glycophospholipids also reduced the transition temperature from gel to liquid-crystalline phase (Tm) of dipalmitoylphosphatidylcholine (DPPC) bilayers. Interestingly, incorporation of NANL-DOPE induced a decrease of membrane fluidity of DPPC bilayers in the gel phase while other glycophospholipids had no effect. Also, low level of NANL-DOPE but not other glycophospholipids increased the transition temperature (TH) from liquid-crystalline to hexagonal phase of dielaidoylphosphatidylethanolamine bilayers. These results showed that NANL-DOPE with a highly hydratable headgroup which provides a strong stabilization activity for the L alpha phase of phospholipid membranes, may also be involved in specific interactions with neighboring phospholipids via its saccharide moiety. PMID- 1457457 TI - Effect of bovine prothrombin fragment 1 on the translational diffusion of phospholipids in Langmuir-Blodgett monolayers. AB - Previous work has shown that bovine prothrombin fragment 1 binds to supported planar membranes composed of phosphatidylcholine and phosphatidylserine in a Ca(2+)-specific manner (Tendian et al. (1991) Biochemistry 30, 10991; Pearce et al. (1992) Biochemistry 31, 5983-5995). In the present work, fluorescence pattern photobleaching recovery has been used to examine the effect of membrane-bound fragment 1 on the translational diffusion coefficients of two fluorescent phospholipids in fluid-like phosphatidylserine/phosphatidylcholine Langmuir Blodgett monolayers. The results show that saturating concentrations of fragment 1, in the presence of Ca2+, reduce the diffusion coefficient of nitrobenzoxadiazolyl-conjugated phosphatidylserine (NBD-PS) and nitrobenzoxadiazolyl-conjugated phosphatidylcholine (NBD-PC) by factors of approximately four and two, respectively. Ca2+ or fragment 1 alone do not have a statistically significant effect on NBD-PS or NBD-PC diffusion. In addition, a nonspecific protein (ovalbumin) does not change the diffusion coefficients of the fluorescent phospholipids either in the absence or presence of Ca2+. The fractions of the fluorescent phospholipids that are laterally mobile are approximately 0.9 for all samples. These results are interpreted with several models for possible mechanisms by which extrinsically bound proteins might retard phospholipid diffusion in membranes. PMID- 1457458 TI - Comparative theoretical study of the conformations of amphotericin methyl ester and amphotericin B polar heads in the presence of water. AB - Amphotericin methyl ester (AmE) is an interesting derivative of amphotericin B (AmB) because of its enhancement of selectivity against the fungicells. Both AmB and AmE molecules differ by the structure of their polar heads. This work deals with a theoretical study of conformations of the polar head of AmE in the presence of hydration water molecules. The results will be compared with our previous work concerning AmB. PMID- 1457459 TI - Ethanol effects on the stratum corneum lipid phase behavior. AB - The stratum corneum is considered to be the diffusional barrier of mammalian skin for water and most solutes. The intercellular lipid multilayer domains of the stratum corneum are believed to be the diffusional pathway for most lipophilic solutes. Fluidization of the lipid multilayers in the presence of ethanol is frequently conceived to result in enhanced permeation. Current investigations address the effect of ethanol on the phase behavior in terms of stratum corneum lipid alkyl chain packing, mobility and conformational order as measured by Fourier transform infrared (FTIR) spectroscopy. Phospholipid multilamellar vesicles were also studied as model systems. There appeared to be no effect of ethanol on either the solid-solid phase transition or the gel phase interchain coupling of the stratum corneum lipids. However, there was a reduction in the mobility of the alkyl chains in the presence of ethanol. Possible mechanistic relationships between the current FTIR spectroscopic results with available literature data of ethanol induced lipophilic solute penetration enhancement through the skin are discussed. PMID- 1457460 TI - The stratum corneum lipid thermotropic phase behavior. AB - The stratum corneum, the outermost layer of mammalian skin, is considered the least permeable skin layer to the diffusion of water and other solutes. It is generally accepted that the intercellular lipid multilayer domain is the diffusional pathway for most lipophilic solutes. Fluidization of the lipid multilayers is believed to result in the loss of barrier properties of the stratum corneum. Current investigations address the lipid thermotropic phase behavior in terms of lipid alkyl chain packing, mobility and conformational order as measured by Fourier transform infrared (FTIR) spectroscopy. A solid-solid phase transition is observed with increased alkyl chain mobility followed by a gel to liquid-crystalline phase transition near 65 degrees C. These results further elucidate the role of lipid fluidity that may contribute to the transport properties of the stratum corneum. PMID- 1457461 TI - The functions of Myc proteins. AB - The functions of Myc proteins have remained a mystery for a number of years. Recent data have now provided us with a clear working hypothesis of how myc may act. What appears to be still missing is a link between the biochemical properties of this oncoprotein and its observed biological effects. Further research will be necessary to fill this void. PMID- 1457462 TI - The interleukin-2 receptors: insights into a complex signalling mechanism. PMID- 1457463 TI - Oncoprotein phosphorylation and cell cycle control. PMID- 1457464 TI - Genes and functions: trapping and targeting in embryonic stem cells. PMID- 1457465 TI - Transcriptional regulators of Drosophila embryogenesis. PMID- 1457466 TI - Regulation of proto-oncogene mRNA stability. PMID- 1457467 TI - Determination of (22R,S)budesonide in human plasma by automated liquid chromatography/thermospray mass spectrometry. AB - (22R,S)Budesonide was isolated from human plasma by solid-phase extraction. Switching from reversed-phase conditions during sample application and washing to normal-phase conditions during elution afforded a very clean extract. Budesonide was derivatized with acetic anhydride to form the 21-acetyl derivative before analysis by reversed-phase liquid chromatography combined with thermospray mass spectrometry. Deuterium-labelled budesonide was used as internal standard. Standard samples prepared in human albumin solution were used for the calibration curve. An automated liquid chromatography/mass spectrometry system, allowing unattended overnight operation, was used for routine analysis. The recovery of budesonide from plasma was 88.9 +/- 5.9% (mean +/- SD) and the method was linear over the range 0.30-30 pmol (amount analysed), corresponding to plasma concentrations of 0.10-10 nmol l-1. Budesonide could be measured down to 0.10 nmol l-1 with a within-day variation of 10-18% (CV). The error was less than +/- 15% at 0.10 nmol l-1 and less than +/- 7% at concentrations of 0.20 nmol l-1 or higher. The total imprecision between days was 9% (CV) at a concentration of 0.30 nmol l-1. PMID- 1457468 TI - Identification and quantitation of an oxidative metabolite of labetalol in sheep: pharmacokinetic and metabolic implications. AB - A sensitive and selective assay has been developed for the identification and quantitation of 3-amino-1-phenyl butane (3-APB), a metabolite of labetalol, in biological fluids using electron impact gas chromatography/mass-selective detection. Samples were extracted with n-hexane, derivatized with heptafluorobutyric anhydride and chromatographed on a cross-linked fused-silica capillary column. A positive EI spectrum was obtained using a mass-selective detector. Identification of the metabolite was accomplished using an authentic standard; quantitation was performed in the selected ion monitoring mode using ions m/z 345 (M+) and 132. The assay was linear over the calibration range of 0.5 1000 ng of the analyte and the intra-sample coefficients of variation were less than 12% in all cases. The absolute recovery of 3-APB following extraction from urine and bile was found to be 102.9 +/- 4.9% and 98.3 +/- 1.45% (mean +/- SEM) respectively. The minimum quantitation limit of the assay was 0.5 ng ml-1 (approximately 2 pg injected). Application of the assay in a pharmacokinetic pharmacodynamic study of labetalol in sheep is demonstrated. The metabolite was detected in urine and bile samples obtained from adult non-pregnant sheep following labetalol administration. The cumulative amount of 3-APB excreted in urine over 24 h was found to be 71.55 micrograms in one animal following a 100 mg dose of labetalol. Evidence for biliary excretion, glucuronidation and sulfation of 3-APB was also found. PMID- 1457469 TI - Gas chromatographic/mass spectrometric analysis of stable isotopes of 3 methylhistidine in biological fluids: application to plasma kinetics in vivo. AB - A simple and rapid method for measuring 3-methylhistidine (3MH) in plasma and urine is described. Internal standard, 1-methylhistidine (1MH), was added to plasma, acidified and absorbed onto cation-exchange columns. It was then eluted from columns, dried, and derivatized for gas chromatography/mass spectrometry. A major fragment of 3MH was monitored at 238 u and 3-methyl-(methyl-2H3)histidine (d3-3MH) (used for in vivo kinetics) at 241 u, whereas 1MH was monitored at 340 u and eluted 0.5 min later than 3MH. Standard curves for plasma analysis were linear and nanamole amounts of 3MH in plasma were determined with a precision of 3.5%. 3MH was also quantitated in urine; however, because of substantial amounts of 1MH, (18O2)1MH was used as the internal standard. Nanamole amounts of 3MH were determined in urine with a precision of 2.7%. Application of the 3MH analytical method was used to develop a kinetic compartmental model by using the stable isotope of 3MH, d3-3MH. Cattle, like humans, quantitatively excrete 3MH in the urine. A young bovine was injected with d3-3MH and the enrichment curve in plasma was evaluated in order to obtain a steady-state production rate of 3MH. The decay curve was modeled through the use of NIH-SAAM modeling program. The kinetics of d3-3MH from plasma were adequately described by a three-pool compartmental model. The de novo production rate of 3MH estimated in the calf was 665 mumol per day. This corresponded to an estimated fractional turnover rate of 1.56% per day, which was similar to estimates obtained from urine collections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457470 TI - Analysis of peptides of human seminal plasma by mass spectrometry. AB - A procedure is described to isolate peptides from complex biological fluids (e.g. seminal plasma) in pure form within a short time. The sequence of the isolated peptides was determined by liquid secondary ion mass spectrometry in combination with enzymatic cleavage reactions. The method was used for the structure elucidation of a peptide of molecular weight 2766 u with an N-terminal pyroglutamine residue. PMID- 1457471 TI - Fragmentations of dipeptides in plasma desorption mass spectrometry: new rules for the sequence elucidation of oligopeptides. AB - 252Cf plasma desorption mass spectrometry is well suited for determining both composition and sequence of unknown small oligopeptides. A systematic study of a large number of dipeptides first leads to establishing common rules of fragmentation from positive ion mass spectra. These rules are then applied to the sequence elucidation of larger peptides. PMID- 1457472 TI - Laser microprobe mass spectrometric identification of cyclosporin-induced intrarenal microliths in rat. AB - Using laser microprobe mass analysis (LAMMA), the composition of 'micro calcifications (dystrophic type)' or 'metastatic calcifications', previously described in rats given high doses of cyclosporin, have been identified. Female Wistar rats given 12.5, 25 or 50 mg kg-1 per day of cyclosporin in olive oil by gastric gavage developed intrarenal calcifications detected by silver nitrate staining (von Kossa) in the outer medulla after two weeks. The calcifications stained red with periodic acid-Schiff reagent and appeared to be intraluminal microliths with concentric laminations. They could be identified by LAMMA as calcium phosphate (hydroxyapatite), indistinguishable from undecalcified bone. These studies indicate that intraluminal obstruction by calcium phosphate microliths, similar to that seen with magnesium depletion or high phosphate diets, may contribute to renal damage in rats given high-dose cyclosporin. LAMMA appears to be an appropriate technique for identifying both the elemental and organic moieities of intrarenal calcium deposits. PMID- 1457473 TI - [Space-occupying lesions of the orbit: modern imaging diagnosis]. AB - The paper summarises imaging of orbital diseases by CT and MRI. As localisation is an important clue to differential diagnosis in orbital tumours, the different pathologies are described according to sites of prevalent occurrence. Morphological criteria of orbital pathology are described, and the more frequent entities are illustrated. PMID- 1457474 TI - [Quality control of laser imagers]. AB - Multiformat imagers based on laser systems are used for documentation in an increasing number of investigations. The specific problems of quality control are explained and the persistence of film processing in these imager systems of different configuration with (Machine 1: 3M-Laser-Imager-Plus M952 with connected 3M Film-Processor, 3M-Film IRB, X-Rax Chemical Mixer 3M-XPM, 3M-Developer and Fixer) or without (Machine 2: 3M-Laser-Imager-Plus M952 with separate DuPont Cronex Film-processor, Kodak IR-Film, Kodak Automixer, Kodak-Developer and Fixer) connected film processing unit are investigated. In our checking based on DIN 6868 and ONORM S 5240 we found persistence of film processing in the equipment with directly adapted film processing unit according to DIN and ONORM. The checking of film persistence as demanded by DIN 6868 in these equipment could therefore be performed in longer periods. Systems with conventional darkroom processing comparatively show plain increased fluctuation, and hence the demanded daily control is essential to guarantee appropriate reaction and constant quality of documentation. PMID- 1457475 TI - [The influence of the spectrum and the type of exposure on the contrast of double sided coated x-ray film]. AB - The present article describes the circumstances concerning the use of testing aids such as sensitometers with one-sided exposure. It is shown which phenomena must be considered if radiographic films coated on both sides are exposed with a) standard pocket sensitometers (one-sided exposure), b) lab sensitometers (double sided exposure to ANSI Ph 2.9 [1964]), c) x-radiation in the cassette, intensifying screen and film system (to DIN 6867 T 1). The effect of the emission spectrum on the resulting contrast factor is described. The importance of different emulsion technologies (e.g. orthochromatic anticross-over films) for the contrast factor with one-sided exposure is described. The cross-over factor (c.o.), the apparent variation in sensitivity of the front and back emulsion with one-sided exposure, is the cause of the reduction in the contrast factor (G average) as against double-sided exposure: delta G(%) = c.o.2 x 10(3)/8.4 PMID- 1457477 TI - [Potentialities and limitations of MR angiography in the imaging of intracranial aneurysms]. AB - The potential value of MR angiography in imaging of intracranial aneurysms was analyzed in seven patients. Six cases were confirmed by angiography or computed tomography. In one patient MR angiography was not useful in distinguishing bleeding from an aneurysm. Five aneurysms were imaged by 3D angiography, one was diagnosed by 2D angiography. The extent of thrombosis was evaluated by selective presaturation. MR angiography was a useful non-invasive method in imaging of intracranial aneurysms. However, for complete work-up angiography is mandatory. PMID- 1457476 TI - [The place of computed tomography and magnetic resonance tomography in the diagnosis of bone sequestra]. AB - Conventional radiographs of 45 patients with chronic osteomyelitis, mostly of posttraumatic origin, were compared with computed tomography (CT) and operative findings. In addition, magnetic resonance imaging (MRI) was performed in 6 of these patients. In 28 patients (65%) bony sequestra were identified and in most cases histologically confirmed by surgical exploration. CT proved to be the method of choice for the preoperative diagnosis of sequestra in patients with chronic osteomyelitis. MRI provided no significant additional diagnostic information, its advantage appears to be a more detailed and accurate imaging of the extent of the intra- or extraosseous inflammation, thereby facilitating surgical planning. PMID- 1457478 TI - [Differential diagnosis of angiodysplasias using angiography and CT with special reference to the MR tomographic aspects]. AB - The basic prerequisite for a rational therapy of angiodysplasia is differentiated diagnostics, especially the differentiation between arteriovenous malformations, haemangiomas, and venous malformations. Angiography reveals the arterialisation, arteriovenous fistulas, CT infiltrations of bone and soft-tissue. MRT demonstrates completely the extent of haemangiomas because of its bright signal intensity in the T2-weighted images. Hence, differentiation of malignant vessel tumours and malformations with rapid blood flow is possible, because the signal intensity is much lower in MRT. The three supplementary methods allow a correct diagnosis of angiodysplasia. PMID- 1457479 TI - [Roentgeno-morphologic changes in the bones of battered children]. AB - The demonstrated characteristic bone lesions should raise the suspicion of "battered child syndrome". The important role of the radiologist is stressed. PMID- 1457480 TI - [The problem of diffuse cranial hyperostosis following cerebral trauma in early childhood--a case report]. AB - This is a report on an uncommon case of cranial hyperostosis with generalised considerable thickening of the calvarium. As a consequence of a cerebral trauma in early childhood the patient developed an intracerebral haematoma. Subsequently a disturbance of brain growth with posttraumatic, symptomatic epilepsy was noted. The anticonvulsant long-term treatment was mainly based on dilantin (diphenylhydantoin). Two different reasons for the distinct skull changes in the present case must be taken into consideration. Firstly, a widening of the dipole induced by dilantin, and secondly, a compensatory thickening of the vault with alterations of the skull base as seen in cerebral atrophy or after relieved hydrocephalus. These mechanisms are discussed with regard to the relevant literature. PMID- 1457481 TI - [Pachymeningeosis(-itis) haemorrhagica chronica interna]. AB - A case of chronic internal haemorrhagic pachymeningeosis, a rare disease with uncharacteristic clinical appearance is presented. Derived from pathomorphological and histological findings, the typical CT appearance is described and main differential diagnoses are marked off by their characteristic criteria. PMID- 1457482 TI - [Lymphangioleiomyomatosis]. AB - A female patient is presented with a history of asthma, recurrent pneumothoraces and chylothoraces. A CT of the chest revealed typical thin-walled cysts of lymphangioleiomyomatosis. The suggested diagnosis was confirmed histologically. CT is exceptionally suited to narrow down the scope of differential diagnosis of interstitial lung diseases. PMID- 1457483 TI - [Lobular carcinoma of the breast in magnetic resonance tomography. A case report]. AB - The invasive lobular carcinoma of the breast, the incidence of which is 10-15 per cent, occupies a special position in respect of histological differentiation and biological behaviour. No MR signal enhancement was seen after contrast medium application in the tumoral tissue in the case described here, namely, an invasive lobular carcinoma of the breast of 2 cm size. Hence, it is not always possible to exclude with absolute certainty the presence especially of an invasive lobular carcinoma of the breast in the absence of contrast medium uptake. PMID- 1457484 TI - [Iopamidol-300/370 in galactography--a clinical comparative study]. AB - From 12. 1988 to 6. 1990 we carried out on 27 patients at the Department of Gynaecology of the University of Freiburg an open study to compare the two water soluble, nonionic, monomeric contrast agents (Iopamidol-300 corresponding to Solutrast-300 and Iopamidol-370 corresponding to Solutrast-370) with different osmolality (616 mosm/kg H2O resp. 799 mosm/kg H2O) and concentration (300 mg I/ml resp. 370 mg I/ml). It is a remarkable fact that the contrast quality in the x rays was higher for Iopamidol-300. Complications such as hypersensitivity reactions or local irritations were not recorded. Iopamidol-300 was found to be the best tolerated of the two contrast media in respect of mildest intensity of pain. PMID- 1457485 TI - [Advice on the x-ray positioning of the upper and the lower leg]. AB - Roentgenographic images of the femur and tibia to demonstrate the bones in two true right-angled projections (anteroposterior, lateral view) can be obtained by using a small hydrostatic level with two levels positioned at right angles against each other. By taping the small plastic device to the skin of the leg under examination, rotation of the limb between the two x-ray exposures can be controlled and adjusted to exactly 90 degrees. Compared to other common positioning procedures (rotation of the leg to approximately 90 degrees by the patient; angulation of the x-ray tube to 90 degrees around the leg) this method yields the highest accuracy of adjustment. PMID- 1457486 TI - The health assessment questionnaire 1992: status and review. AB - Over 100 papers describing and utilizing the Stanford Health Assessment Questionnaire (HAQ) have been published since 1980. A brief overview of the HAQ is presented along with a guide to the accumulated literature. The topics covered include: studies using the disability, pain, economic, and drug side effect dimensions of the HAQ; reliability and validity studies; applications to various rheumatic diseases; language adaptations; modifications and derivative scales; studies correlating the HAQ with sociodemographic, health status, laboratory, and physical measures; and randomized controlled trials and observational studies using the HAQ. A few comments regarding future directions for research are also presented. PMID- 1457487 TI - Sensitivity to change of the health assessment questionnaire (HAQ) and other clinical and health status measures in rheumatoid arthritis: results of short term clinical trials and observational studies versus long-term observational studies. AB - To obtain evidence concerning short-term and long-term efficacy of clinical and health status measures in rheumatoid arthritis (RA), we conducted two observational studies--a 6-month study of 233 patients receiving methotrexate and a 10-year study of 157 patients receiving multiple treatments in a rheumatic disease clinic. Results of the 6-month study yielded effect sizes for treatment similar to the meta-analyses reported by Felson [corrected] et al. (Arthritis Rheum 33:1449-1461, 1990) and the controlled trials of methotrexate reported by Weinblatt et al. (Arthritis Rheum 33:330-338, 1990), suggesting that observational studies provide valid measurements of treatment effect. The effect size for the Health Assessment Questionnaire (HAQ) was 0.5. By contrast, the 10 year study suggested that standard clinical variables changed little and were not useful in assessing RA outcome, while the effect size of the HAQ was -2.39. These data continue to underscore the differences between short-term trials and the long-term outcome of RA, and suggest an important place for the HAQ or similar instruments in all phases of RA evaluation and assessment. PMID- 1457488 TI - Comparison and sensitivity to change of self-report scales to assess difficulty, dissatisfaction, and pain in performing activities of daily living over one and five years in rheumatoid arthritis. AB - We analyzed the longitudinal sensitivity to change of three self-report activities of daily living (ADL) scales over 1 and 5 years in 982 patients with rheumatoid arthritis (RA) from 15 private practices. Over 1 year, the ADL difficulty status worsened in 28.3% of the patients, remained the same in 50.2%, and improved in 21.5%. Over 5 years, 41.3% worsened, 38.8% stayed the same, and 19.9% were improved. Similar percentages for 1- and 5-year changes were found for the ADL dissatisfaction and pain scales. The effect sizes for change over 1 and 5 years for the ADL difficulty, dissatisfaction, and pain scales were--(-)0.05, 0.01, and -0.02, and -0.28, -0.20, and -0.14, respectively, indicating small to moderate declines. These data indicate that the three ADL scales are sensitive to change in status, and ADL change status scores after 1 and 5 years were significantly correlated with each other (r = 0.49-0.68, all p < 0.001). Monitoring of these three constructs may be helpful in the longitudinal evaluation of some patients with RA. PMID- 1457490 TI - Scoring methods and application of the activity record (ACTRE) for patients with musculoskeletal disorders. AB - The National Institutes of Health (NIH) Activity Record (ACTRE) has been used to document daily activities in patients with musculoskeletal disorders. Quantification of the amount of time spent resting and physically active, the intensity of pain and fatigue associated with patterns of activities, and motivational considerations are possible with the ACTRE. Scoring has been streamlined to permit identification of the amount of pain, fatigue, and motivational factors as they relate to activity patterns (e.g., rest and physical activity). The ACTRE provides a performance-based, quantifiable measure of daily activity. PMID- 1457489 TI - Does musculoskeletal function deteriorate in a predictable sequence in the elderly? AB - A variety of functions decline with aging, but whether losses occur in a predictable sequence is unknown. Improved understanding might facilitate the early detection and possible prevention of functional deterioration. We assessed self-reported difficulty with functional tasks in 288 community-dwelling elderly aged 65 to 97. We hypothesized that the ability to perform tasks involving strength, skill, and endurance (run errands, shop, yardwork or housework) would be lost first, followed by activities requiring less strength or mobility (rise from a chair with no hands, walk), followed by easier, but essential tasks (pick up clothes, rise from bed, lift a cup to the mouth). The patterns of decline were evaluated with Guttman scalograms. Picking up clothes and walking were reversed from the predicted order. Scale reliability was 0.92, indicating that functional decline is ordered; 75% of subjects fell into one of the modal sequence types. Analysis by self-reported presence of arthritis showed that 83% of nonarthritic subjects fit the predicted patterns (reliability = 0.95) versus 65% of arthritic subjects (reliability = 0.86), who tended to lose hand ability out of sequence. Sequential functional loss scales may tell more than the typical simple summation of functional loss, and may have predictive value to the clinician monitoring an elderly patient. If the sequence is accelerated or out of order, such as was seen in patients with arthritis, it may indicate the need for intervention. Examination of sequences of loss may help characterize adaptations to impairment and differences among subgroups. PMID- 1457491 TI - Arthritis problem indicator: preliminary report on a new tool for use in the primary care setting. AB - Improving the quality of life for people with rheumatic disease involves timely identification of problem areas and application of appropriate interventions. In response to a 1987 Commonwealth of Pennsylvania study, which reported a wide variety of unmet needs in arthritis patients and their families, the Arthritis Problem Indicator (API) was developed. It is a single-page, self-report, low-cost tool. A mixed rheumatology population (n = 50) and their primary care physicians participated in a pilot study. The study revealed that the seven most common areas of patient concern were pain, weight control, sleep, mobility/walking, activities of daily living, community access, and depression/anxiety. The physicians reported that the patient's answers on the API led them to initiate new treatment or referral for 32% of the patients. The physicians also stated that for 80% of the patients, the API was helpful in providing information about the patient. The API is easily interpreted by health professionals and designed to be an indicator of problem areas frequently associated with arthritis. PMID- 1457492 TI - Do self-reported arthritis symptom (RADAR) and health status (AIMS2) data provide duplicative or complementary information? AB - This study assessed whether self-report measures of symptoms and functional health status provide unique outcome information, or whether functional status assessments primarily serve as a proxy for self-reported arthritis symptoms. Symptom scores of 138 individuals with rheumatoid arthritis (RA) collected with the Rapid Assessment of Disease Activity in Rheumatology (RADAR) measure were compared with same-day functional health scores collected with the recently revised Arthritis Impact Measurement Scales (AIMS2). Correlational and factor analyses revealed that self-assessed arthritis symptoms, physical function and work impact, psychological status, and social health each made independent contributions to outcome. Satisfaction with health status was shown not to be independent of symptoms, functional capacity, or psychological status. It is important to document that self-reported symptom and health status information, when collected concurrently, provides complementary rather than duplicative information. PMID- 1457493 TI - Quality of life and policy analysis in arthritis. AB - Problems in the American health care system have stimulated interest in cost effectiveness methodologies. However, there is little consensus on how to define a common unit of health outcome. Many measures used in policy studies consider only mortality and do not fully capture the significant impact of disease-related dysfunction. The impact of conditions, such as osteoarthritis, that have little impact on mortality rates but substantial impact on functioning and well-being may be underestimated in these analyses. In this article, we propose a measurement and policy model that is based on a theoretical conceptualization of health outcome. The model considers the impact of disease and its treatment in terms of both morbidity and mortality. The value of the model for clinical trials, population assessments, and policy analysis is reviewed. A public policy application of the model in Oregon is briefly described. PMID- 1457494 TI - Characterizing the meaning of psychological distress in rheumatoid arthritis. AB - Symptoms of depression are frequently reported by people with rheumatoid arthritis (RA). To advance our understanding of how best to assess and treat these symptoms, their meaning must be elucidated. This article explores two possible meanings for the emotional distress of RA patients reported on the Center for Epidemiological Studies Depression (CES-D) scale: (1) Certain CES-D scale items may inflate actual depressive symptom scores. (2) Depressive symptoms are experienced and/or expressed in unique ways in an RA population due to the presence of chronic physical symptoms. In this study of 988 people with RA, it was found that there is some modest inflation of the CES-D scale due to the items of "having difficulty getting going" and "everything was an effort." However, irrespective of the modest inflation of the scale, there is evidence that distress in RA is not a static concept. Distress in this RA population was expressed differently from that of a community population, and within the RA population, distress was expressed differently over time. PMID- 1457495 TI - Pathology of malignant lymphomas. AB - Although the subject is now seldom formally addressed, much of the pathologic research into malignant lymphoma is still tacitly directed at developing a rational and reproducible classification. Pure morphology, while remaining of critical importance in the diagnosis of malignant lymphomas, has been exhausted as a means of understanding the biology of these tumors, which must be the eventual basis of a firm, enduring and clinically relevant classification. Thus, histopathologists have turned first to immunohistochemistry and now to molecular genetics to make sense of their morphologic observations. Correlation of various genetic (including oncogenetic) rearrangements with morphology has preoccupied pathologists this past year and has led to important advances in the understanding of B- and T-cell lymphomas. Lymphomas occurring in a setting of immunodeficiency, whether therapeutically induced or acquired, have received special attention, and the possible role of the Epstein-Barr virus in their pathogenesis has induced pathologists to develop exciting in situ molecular hybridization techniques for its identification in tissues. The certainties underlying the diagnosis and classification of Hodgkin's disease (in which Epstein-Barr virus also appears to play a role), formally the only truly secure area for pathologists, have been disturbed, and the borderline between Hodgkin's disease and non-Hodgkin's lymphoma is now seriously blurred. The lymphoma pot has been well and truly stirred; we must now wait to see what the new sediment offers. PMID- 1457496 TI - Advances in the treatment of Hodgkin's disease. AB - Through the careful application of appropriate staging procedures and treatment modalities, at the beginning of the 1990s about 75% of patients with Hodgkin's disease can expect long-term remission or even cure. At present, radiotherapy remains the best therapeutic option for localized stages while advanced disease is cured by chemotherapy alone or chemotherapy combined with irradiation. In this decade, the challenge in the management of Hodgkin's disease will probably be represented by an optimal use of reasonably short-term chemotherapy regimens combined with limited-field irradiation in early stages and by an accurate evaluation of the best chemotherapy regimens for advanced disease. In the search for the optimal approaches to improve current therapeutic results, appropriate considerations should be given to the identification of effective treatment modalities with a minimum amount of acute and late toxicity. PMID- 1457497 TI - T-cell leukemia-lymphoma and mycosis fungoides. AB - Notable efforts have been made to relate aspects of the cell biology of T cells to the pathology, diagnosis, and treatment T-cell neoplasms. In particular, the application of molecular biologic tools to these areas has already allowed the generation of patient-specific markers for disease. A case can be made that a knowledge of the distinctive natural history of T-cell neoplasms should influence choices of treatment. Additional insights into the relevance of the human T-cell leukemia-lymphoma virus family to human disease have been recorded, and an important association of cutaneous T-cell lymphoproliferative disorders with human immunodeficiency virus infection has been documented. PMID- 1457498 TI - Chemotherapy for non-Hodgkin's lymphoma. AB - The term non-Hodgkin's lymphoma (NHL) refers to a diverse group of illnesses that have in common a high frequency of chemotherapy sensitivity. In fact, high-grade NHL was among the first cancers to be cured with chemotherapy. Although the curability of patients with low-grade NHL remains debatable, all patients with intermediate- and high-grade NHL should be approached with curative intent, even if they present with advanced disease. Our ability to treat patients with NHL is steadily improving. There have been significant advances in our understanding of the biology of the disease and our ability to predict treatment outcome. New treatments and innovative uses of already available treatments are regularly reported. This paper reviews the highlights of the past year's literature regarding the treatment of patients with NHL. PMID- 1457499 TI - Biologic response modifiers: therapeutic approaches to lymphoproliferative diseases. AB - Some biologic agents have proven effective in the treatment of lymphoproliferative diseases by stimulating host antitumor immunity or by applying active antitumor properties that specifically or nonspecifically effect tumor growth or tumor survival. These agents include interferons, which regulate cell gene expression, structure, and function; interleukin-2, which has several functions related to lymphoproliferation and mediation of lymphoid cell transport; anti-idiotype antibodies, which appear to cause a specific antiproliferative response against the patient's tumor; anti-idiotype vaccines, which produce cyclic complementary binding sites and idiotypes to induce specific immunity to tumors with resultant antitumor activity; radioisotope labeled monoclonal antibodies, which directly deliver tumoricidal doses of radiation to tumors, sparing normal tissue toxicity; and monoclonal antibody-immunotoxin conjugates, which directly deliver tumoricidal doses of radiation to tumors, sparing normal tissue toxicity. Encouraging results have been seen in clinical studies with these agents and much knowledge has been gained regarding the mechanisms involved. These findings dictate ongoing therapy modifications to produce continuing progress in the therapeutic applications of biologic agents in lymphoproliferative disease processes. PMID- 1457500 TI - Prognostic factors in non-Hodgkin's lymphoma. AB - There is an emerging consensus on the importance of identifying non-Hodgkin's lymphoma patients with different prognoses so that these patients can be optimally treated and the relative benefits of different therapeutic approaches can be adequately assessed. This review of recent publications on prognostic factors in lymphoma will summarize papers identifying: 1) clinical features associated with prognosis in specific subgroups of lymphoma patients; 2) the prognostic significance of pathologic and immunologic subclassification; 3) prognostic features predictive for relapse from complete response; and 4) newly identified prognostic features, including cytogenetic abnormalities, serologic parameters, and aberrant expression of adhesion molecules. PMID- 1457501 TI - Cancer in AIDS. PMID- 1457502 TI - Clinical aspects of Kaposi's sarcoma. AB - Kaposi's sarcoma is the most common tumor found in patients with the acquired immunodeficiency syndrome. This opportunistic neoplasm has characteristics of a sexually transmitted disease. Growth factors, cytokines, immune suppression, and interaction with infectious organisms all appear to play a role in the pathogenesis of this enigmatic disorder. The manifestations of Kaposi's sarcoma are protean, and lesions may appear at any time in the course of human immunodeficiency virus disease, remain localized and asymptomatic, or spread aggressively and cause morbidity. Treatment, which must be individualized, ranges from observation, local therapy with cosmetic makeup, and cryotherapy with liquid nitrogen or local intralesional injection of agents, to radiotherapy and systemic therapy with interferon-alpha and cytotoxic chemotherapy. PMID- 1457503 TI - The epidemiology of acquired immunodeficiency syndrome-related lymphomas. AB - Approximately 3% of acquired immunodeficiency syndrome cases present with non Hodgkin's lymphoma. By 6 to 8 years after human immunodeficiency virus infection, lymphoma risk is elevated 100-fold, and the risk approaches 1% per year following acquired immunodeficiency syndrome diagnosis. The proportions presenting as lymphoma differ by age, sex, and race, with relative rates being higher in older persons, males, and whites. The differences are similar in magnitude and direction to those seen in non-human immunodeficiency virus-infected persons and account for the variation by risk group. The relative risk of high-grade lymphoma is greatest, but significant increases are also seen for some intermediate-grade tumors. At diagnosis, persons with Burkitt's lymphoma, more common in children, have significantly higher average CD4 counts than those with immunoblastic tumors. Human immunodeficiency virus-associated lymphoma risk is probably related to dysregulation of the immune system leading to uncontrolled proliferation of transformed cell clones and subsequent genetic accidents. Environmental factors are unlikely to be important. By 1994, 10% of all lymphomas will be human immunodeficiency virus related, but this proportion will increase in the future. New approaches to the therapy of lymphoma are needed for this tumor, which we can neither prevent nor adequately treat. PMID- 1457504 TI - Clinical aspects of human immunodeficiency virus-related lymphoma. AB - As patients with human immunodeficiency virus infection live longer because of better antiretroviral therapy and infection prophylaxis, the incidence of non Hodgkin's lymphoma has increased. The risk increases inversely with CD4 count- the most widely used surrogate marker for progressive immune suppression. Zidovudine itself does not appear to be a risk factor. Patients frequently present with extranodal advanced disease. The central nervous system is the primary site in 10% to 20% of cases. Important prognostic factors are performance status, a prior history of acquired immunodeficiency syndrome, and bone marrow involvement. Therapy is complicated by underlying immunosuppression, opportunistic infection, and poor bone marrow reserve. Progress has been made using colony-stimulating factors and less intensive chemotherapy regimens in systemic non-Hodgkin's lymphoma. Treatment of primary central nervous system lymphoma with radiation therapy has not improved survival. PMID- 1457505 TI - Biologic aspects of human immunodeficiency virus-related lymphoma. AB - A high frequency of lymphoma in human immunodeficiency virus-infected individuals has been reported since the outbreak of the acquired immunodeficiency syndrome (AIDS) epidemic in 1982. In the vast majority of cases, these lymphomas are highly aggressive B-cell, non-Hodgkin's lymphoma of intermediate or high grade of malignancy. AIDS-associated non-Hodgkin's lymphoma are histologically classified as small noncleaved cell lymphoma, large cell immunoblastic plasmacytoid lymphoma, or large noncleaved cell lymphoma. Host factors predisposing to lymphoma development in AIDS patients include decreased immunosurveillance as well as human immunodeficiency virus-induced chronic perturbation of the immune system leading to cytokine overproduction and increased B-cell stimulation. These alterations are associated with the development of multiple oligoclonal B-cell expansions, which are characterized by persistent generalized lymphadenopathy. The presence of Epstein-Barr virus within a persistent generalized lymphadenopathy clone further increases the risk of its neoplastic transformation. The appearance of non-Hodgkin's lymphoma is characterized by the presence of a monoclonal B-cell population displaying several genetic lesions, including monoclonal Epstein-Barr virus infection, c-myc rearrangements, Ras mutations, and p53 inactivation. The number and type of lesions varies among the different types of AIDS-non-Hodgkin's lymphoma, defining multiple alternative molecular pathways in AIDS-associated lymphomagenesis. PMID- 1457507 TI - Risk factors, epidemiology, screening, and prognostic factors in female genital cancer. AB - This review, which due to limitations of space cannot be exhaustive, summarizes the recent literature on risk factors and epidemiology, screening and prognostic factors in a cervical, ovarian, and endometrial cancer. There have been a large number of pertinent publications during this period and this paper summarizes and highlights recent advances in the identification of women at particularly high risk of developing gynecologic cancer, analyzes studies on early detection and screening, and reviews prognostic studies with particular reference to selection of therapy according to risk of relapse and likelihood of benefit. PMID- 1457506 TI - Human immunodeficiency virus as a risk factor in miscellaneous cancers. AB - The association of malignancies, such as non-Hodgkin's lymphoma and Kaposi's sarcoma, with human immunodeficiency virus infection has been recognized since the beginning of the epidemic. However, an increasing number of tumors not diagnostic of acquired immunodeficiency syndrome has been described in this setting. Taking into consideration that survival of patients with human immunodeficiency virus infection is increasing because of improvement of supportive care and better control of human immunodeficiency virus and related opportunistic infections, oncogenic viruses such as human papillomavirus, hepatitis B virus, Epstein-Barr virus, in a setting of prolonged immunosuppression could increase the risk of a variety of malignant tumors. PMID- 1457508 TI - Surgery for gynecologic malignancies. AB - The surgical management of invasive and preinvasive gynecologic malignancies continues to evolve at a brisk pace. Several good techniques are available for the treatment of preinvasive cervical disease, including cryotherapy, loop electrocautery excision, laser therapy, and standard knife conization. The use of radical surgery for early invasive cervical cancer has been extended to older women, and complications have been minimized. There has been a significant trend toward more conservative surgery in the management of invasive vulvar cancer. The new surgical staging system for endometrial cancer has generated much controversy. The importance of thorough surgical staging for ovarian cancer is clear, and our understanding of the role of cytoreduction has increased. The role of new techniques, including operative laparoscopy, is being defined in the management of gynecologic cancers. PMID- 1457509 TI - Radiotherapy for gynecologic malignancies. AB - This review highlights the curative potential of radiation in gynecologic malignancies. The controversies concerning the role of surgery in the management of bulky cervical cancer is discussed. Prognostic factors associated with improved pelvic control with radiation alone are described, particularly the bulk of pelvic disease, which is not accounted for in the current International Federation of Gynecology and Obstetrics staging system. The potential for integration of radiation and chemotherapy into the management of vulvar cancer to improve cosmesis and function as well as to reduce the risk of locoregional recurrence is described. The role of whole abdominal radiation in the management of advanced endometrial and ovarian cancers as well as the role of hyperfractionation to reduce acute morbidity of large abdominal fields is reviewed. Prognostic factors associated with locoregional and distant failure for endometrial cancer are outlined and the new pathologic staging system is critically analyzed. Finally, the treatment of vaginal cancer with radiation alone (external beam plus interstitial-intracavitary radiation) or surgery is reviewed and the prognostic importance of the present modifications to the vaginal staging system are emphasized. PMID- 1457510 TI - Systemic therapy for gynecologic cancer. AB - Over the past year, a number of important papers have appeared in the medical literature dealing with the chemotherapeutic management of gynecologic cancers. Among these papers, several studies have again demonstrated the superiority of platinum-based chemotherapy regimens for ovarian cancer compared with non platinum-containing regimens, and have confirmed the equivalence of carboplatin to cisplatin in advanced disease. A number of trials have reported activity for intraperitoneal chemotherapy regimens in patients with small-volume residual disease. In endometrial cancer, combination cisplatin-based chemotherapy programs have been reported to achieve an overall 40% to 50% objective response rate. Although induction chemotherapy has been advocated in the management of advanced localized cervical cancer, this conclusion has yet to be supported by the results of randomized trials. The etoposide, methotrexate, dactinomycin, cyclophosphamide, vincristine regimen has been demonstrated to be highly effective in patients with high-risk gestational trophoblastic tumors. Finally, a recent report has demonstrated that it is possible to perform conservative surgery in patients with germ cell tumors to preserve fertility without compromising therapeutic efficacy. PMID- 1457512 TI - Lymphoma. PMID- 1457511 TI - Biology and therapy with biologic agents in gynecologic cancer. AB - Growth of epithelial ovarian cancer is influenced by several factors including transforming growth factor-alpha and transforming growth factor-beta, macrophage colony stimulating factor, tumor necrosis factor-alpha, interleukin-1 and interleukin-6, c-erb B-2 (HER-2/neu), and mutant p53. Continued expression of the epidermal growth factor receptor, new expression of c-fms, and overexpression of HER-2/neu are associated with a poor prognosis. A number of cytokines have been used to treat patients with ovarian cancer, including interferon-alpha, interferon-gamma, tumor necrosis factor-alpha, and interleukin-2. Judging from preclinical models, interferon-gamma may be more active than interferon-alpha against human ovarian cancer. Although tumor necrosis factor-alpha can stimulate proliferation of some ovarian cancers, the cytotoxic activity of tumor necrosis factor-alpha has been amplified ex vivo by inhibitors of protein synthesis. Similar heterogeneity exists with regard to interleukin-1 where stimulation or inhibition of cell proliferation has been observed. Tumor-infiltrating lymphocytes from ascites fluid contain cells capable of major histocompatibility complex-restricted and major histocompatibility complex-nonrestricted cytotoxicity. Tumor-infiltrating lymphocytes and interleukin-2 have been combined with cytotoxic chemotherapy to treat advanced or recurrent disease. Bispecific monoclonal antibodies that react both with T cells and ovarian tumor cells have produced tumor inhibition in human tumor xenografts. Immunotoxins that contain OVB3 and pseudomonas exotoxin have been evaluated in a phase I clinical trial. Dose-limiting central neurotoxicity has been observed without tumor regression. A monoclonal antibody designated OVX1 has been developed against a high-molecular weight mucinlike molecule associated with ovarian cancers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457513 TI - Cancer in AIDS. PMID- 1457514 TI - Gynecologic cancer. PMID- 1457515 TI - Biology of breast cancer and its clinical implications. AB - Several established prognostic factors are used routinely in the clinical management of breast cancer. These factors include extent of axillary lymph node involvement, tumor size, histologic differentiation, and estrogen and progesterone receptor status. Unfortunately, these factors are not perfect predictors of outcome for the individual patient. This review highlights recent advances in the field of breast cancer biology that may ultimately improve our ability to predict prognosis more accurately, select therapy more appropriately, and possibly identify women who are at high risk for breast cancer development. In particular, studies addressing mechanisms of estrogen and antiestrogen resistance, clinical utility of flow cytometry, roles of certain oncogenes and tumor suppressor genes in breast cancer growth, and biologic factors involved in invasion and metastases are reviewed. PMID- 1457517 TI - The surgery of early breast cancer. AB - This review highlights important issues for surgeons treating early breast cancer. The optimal use of ovarian ablation, the value and timing of radiotherapy for breast preservation, and axillary dissection are considered. New information on the importance of local surgery, even for older women, and the biology of small (up to 10 mm), screen-detected cancers has been recently reported. The value of support services for women having breast cancer surgery is stressed. PMID- 1457516 TI - Early detection, epidemiology, and prevention of breast cancer. AB - Control of breast cancer will ultimately be achieved through a better understanding of the epidemiology of the disease and application of primary prevention. Until then, use of screening mammography offers the promise of a 30% reduction in breast cancer mortality, which continues to be shown by screening studies with prolonged follow-up. Biologic markers of cancer risk, including nipple aspirates and cyst fluid, suggest that a complete risk profile can be developed using fluid and tissue obtained from the normal breast. Epidemiologic studies of dietary factors and geographic differences in breast cancer risk continue to provide promising leads relating to the etiology of the disease. Increasing evidence suggests that circulating androgens and estrogens affect breast cancer risk, whereas exogenous estrogen therapy does not increase risk except for small subgroups of women at risk. Increasing understanding of the genetics of breast cancer will have an impact on the disease in the near future. The greatest impact in the short term will come from the use of tamoxifen for primary prevention of breast cancer. The retinoids, particularly N-(4 hydroxyphenyl)retinamide, hold great promise as agents for primary prevention. PMID- 1457518 TI - Systemic adjuvant therapy for breast cancer. AB - Systemic therapy for operable breast cancer can delay the time to recurrence. Recurrence of breast cancer can follow a variable clinical course but will lead to death in virtually all cases. This delay is reflected in an accompanying improvement in overall survival with treatment. Almost 35 years have passed since the introduction of adjuvant chemotherapy, whereas adjuvant tamoxifen trials were begun 17 years ago. In that time, only in a minority of patients has a clear consensus emerged on the appropriate use of adjuvant therapies. Overview analysis from large numbers of controlled clinical trials has produced a much larger data base for examining the effects of hormonal and cytotoxic therapy on the outcome of patients with early-stage breast cancer and provides greater statistical power to detect small differences in particular subgroups of patients, which may not have been apparent in individual studies. Patients with involved lymph nodes are now routinely treated with chemotherapy if they are premenopausal and with tamoxifen if they are postmenopausal, especially if their tumors contain estrogen receptor. More recent trials attempt to examine the use of these therapies outside of these prescribed groups as well as the introduction of new chemotherapeutic agents and dosage regimens, some of which are based on biologic principles of alternating, non-cross-resistant therapy and dose responsiveness. Treatment of node-negative breast cancer remains controversial. Small but real differences in odds of relapse have emerged with adjuvant treatment, although the nature of the risks and benefits remains to be defined. PMID- 1457519 TI - Metastatic breast cancer and its complications. AB - Tamoxifen is now established for use in premenopausal as well as postmenopausal patients. Recent reports have not shown its activity to be enhanced by the addition of either prednisolone, progestogens, or interferon. Reversible ocular toxicity from tamoxifen appears to be more common than had been previously realized. Different schedules giving the same dose intensity of doxorubicin give markedly different pharmacokinetic profiles. Although this does not lead to differences in responses or physical toxicity, it seems to have important implications for quality of life. Taxol is showing impressive activity in advanced breast cancer, and significant response rates have also been reported for carboplatin and podophyllotoxin derivatives. To achieve maximum effectiveness from the cyclophosphamide, methotrexate, and fluorouracil combination, attention to schedule and dose intensity has been shown to be important. No new effective cytotoxic combinations have been described. High-dose chemotherapy requiring bone marrow support remains experimental. Further progress has been made in monitoring the response of metastatic bone disease to treatment. The precise significance for patients of the results in many of the papers reviewed is often uncertain because they lack quality-of-life measures; the importance of this approach is emphasized. PMID- 1457520 TI - Psychosocial aspects of breast cancer. AB - Over the past year, several research areas have been noteworthy. This article discusses several reports on psychiatric morbidity and psychological factors of breast cancer, quality-of-life issues related to breast cancer treatment, and psychological factors in breast cancer screening. An area of increasing interest includes studies examining the psychological status and breast cancer screening practices of women at increased risk of developing breast cancer, primarily as a function of family history. PMID- 1457521 TI - Cisplatin and platinum analogues: recent advances. AB - Cisplatin is a critically important antineoplastic agent employed in treating patients who have a broad spectrum of neoplasms. Resistance to this agent poses a serious clinical dilemma. The objective of this review is to summarize the principal mechanisms that contribute to cytotoxicity by this agent and underlie resistance. Knowledge of these processes provides a rational basis for developing therapeutic strategies to circumvent resistance. PMID- 1457522 TI - Antitumor antibiotics, epipodophyllotoxins, and vinca alkaloids. AB - This paper reviews manuscripts published from June 1991 to June 1992 that, in the author's opinion, have added to the understanding and clinical use of a group of commonly used antineoplastic agents. New developments highlighted include 1) clarification of the mechanism of action of the anthracyclines and epipodophyllotoxins, 2) evaluation of tests used for the early detection of bleomycin pulmonary toxicity, 3) results of studies on the epidemiology and prevention of anthracycline-induced cardiomyopathy, 4) the potential use of therapeutic drug monitoring to predict etoposide toxicity, and 5) identification of drug interactions that alter the pharmacokinetics of the epipodophyllotoxins. PMID- 1457523 TI - Antimetabolites. AB - Research efforts over the past year further elucidate the determinants of sensitivity and mechanisms of resistance to the antimetabolites fluorouracil, methotrexate, and cytarabine. Progress has been made in clarifying the complex regulation of target enzyme expression for these antimetabolites. Advances in analytical methodology should facilitate quantitation of thymidylate synthase content in tumor tissue prior to and following fluorouracil-based therapy. Information concerning the basis for certain drug interactions may guide rational dose rates and schedules for clinical trials. A better understanding of the clinical pharmacology of these agents has suggested strategies to minimize their toxicity while maintaining therapeutic activity. PMID- 1457524 TI - Recent developments in radiotherapy. AB - Radiation oncology is a dynamic discipline. The radiobiologic basis for understanding and anticipating treatment effects continues to grow. Improved understanding is permitting study of altered fractionation regimens and safer integration into the clinic of high-dose-rate brachytherapy. A new agent, SR 4233, may completely revise clinical approaches to tumor hypoxia, especially intermittent (or "dynamic") hypoxia. The availability of computer technology that permits three-dimensional treatment planning with unusual beam and treatment table orientations should result in isodose lines that conform very tightly to desired treatment volumes, permitting higher doses of treatment with acceptable normal-tissue risk. The biology of cytotoxic drug and irradiation interactions and of cytokine and irradiation interactions is an area of growing promise. Combined chemotherapy and radiotherapy treatments have, in the past year, suggested major improvements in the management of esophageal and laryngeal cancer. The importance of local and regional tumor control in contributing to clinical disease course is being understood with increasing clarity, validating the development of technically demanding new approaches to administering irradiation and the use of adjunctive radiotherapy following chemotherapy for selected neoplastic diseases. PMID- 1457525 TI - Modulation of chemotherapy antineoplastic agents with biologic agents: enhancement of antitumor activities by interleukin-1. AB - Cytokines or biologic response modifiers in combination with traditional chemotherapeutic agents can be used as therapeutics in patients with cancer. Biologic response modifiers, which are involved in the control and regulation of a wide variety of physiologic activities, have previously been used primarily to enhance or boost host immunologic function. Although immune modulatory therapeutic approaches are yet to be fully realized, biologic response modifiers have also been considered in combination with cytotoxic drugs for their effects on hematopoietic progenitor cells, tumor cells directly, and microvascular endothelial cells. Interleukin-1 is a multifunctional cytokine that not only activates the immune system but also plays a central role in regulating hematopoiesis, has potent effects on vascular function, and has shown significant antitumor activity alone or in combination with various chemotherapeutic agents. As a result, interleukin-1 is an excellent candidate for combination with conventional antineoplastic drugs toward the design of innovative therapeutic approaches to malignancy. This review examines the studies using preclinical animal tumor models as well as the recent phase I clinical trials and includes an overview of their potential for further application. PMID- 1457526 TI - New biologic agents come to bat for cancer therapy. AB - Biologic therapies are playing an increasingly important role in the treatment of patients with cancer. A better understanding of immune responses to tumors now exists, and more defined reagents are now available including new recombinant cytokines, cultured lymphoid cells of defined specificity, and most recently, vectors containing specific genes that can be introduced either into tumor cells or lymphoid effectors. During this past year, we have observed the reporting of new cytokines identified and tested in humans and the advent of cytokine gene therapy. The successful application of these new reagents either singly or in combination will require significant ingenuity, resources, and intuition over the next decade. PMID- 1457527 TI - Immunotherapy with cytokine gene-transduced tumor cells: the next wave in gene therapy for cancer. AB - Recently, new tumor vaccine approaches were developed in animal systems that modify tumor cells genetically to secrete certain cytokines. Engineering tumor cells to secrete cytokines in a paracrine fashion can induce powerful local cytokine effects without producing significant systemic toxicity. In addition to local inflammation, this approach can alter the presentation of tumor antigens or activation of tumor antigen-specific T lymphocytes, resulting in systemic antitumor immunity. The development of high efficiency gene transfer technologies such as defective retroviral vectors allows for the translation of these preclinical studies to clinical trials. However, before large investments are made in this area of gene therapy, it will be important to demonstrate that the actual gene transfer component of the strategy significantly enhances antitumor immune responses relative to alternative nongenetic approaches. PMID- 1457528 TI - Targeted delivery of biologic and other antineoplastic agents. AB - This review summarizes several strategies under investigation for targeted delivery of antineoplastic agents to tumor cells, which avoids normal tissue damage. Monoclonal antibodies remain the molecules of choice for targeted therapy, and several improvements to immunotargeting are discussed. These improvements include the use of novel radioisotopes, cytokines, new linkers for chemotherapeutic drugs, more potent drugs, and improved immunotoxins. Bifunctional antibodies, in which one antigen-binding site recognizes a tumor associated antigen and the other an antineoplastic agent, have been investigated for radioimmunotherapy and for the activation of cytotoxic cells for targeted immunotherapy. The activation of relatively nontoxic prodrugs by antibody-enzyme conjugates is increasingly being investigated in an effort to reduce the systemic toxicity associated with conventional chemotherapy. Finally, the use of liposomes as carriers of drugs or as activators of macrophages is described. PMID- 1457529 TI - Breast. PMID- 1457530 TI - Therapeutic modalities. PMID- 1457531 TI - [Ethical frontiers of sciences]. PMID- 1457532 TI - [Pregnancy in renal transplant recipients. Long-term evaluation of their children]. AB - The course of eight pregnancies in seven renal transplant patients was analyzed. Immunosuppression consisted of Azathioprine and Prednisone. Pregnancy lasted from 32 to 39 weeks and the fetal development corresponded to the gestational age in every case. There were three cases which had complications during the pregnancy. One case had severe arterial hypertension, proteinuria and pedal edema, which was thought to be due to pre-eclampsia. Another patient had cholestatic jaundice and premature fissure of membranes and the third patient also had this last complication. Four patients had vaginal deliveries and in four cesarean section was performed. Renal function did not deteriorate during any of the pregnancies nor during the follow-up period, but the expected increase in creatinine clearance was not found. Clinical evaluation of the children, 4 months to 8 years of age, did not disclose any abnormalities. PMID- 1457533 TI - Successful pregnancy in a severe hypertensive patient treated with nitrendipine. Case report. AB - Nitrendipine (NIT), a new potent calcium channel blocking agent, was administered to a patient with essential severe (191/119 mm Hg), refractory, and resistant hypertension (HT) to conventional triple drug regime. Three previous pregnancies had been unsuccessful in the past 4 years because of uncontrollable HT and repeated hypertensive crises. NIT (20 mg tablets) was given PO as a single morning dose and 15 months after BP control, she became pregnant again. With a 20 mg/day dose of NIT throughout pregnancy, a healthy 2400 g, 47 cm male boy was delivered by a non-emergency cesarean section at 37 weeks' pregnancy. Both mother and son remain normal months after birth. The results suggest NIT may be considered as an alternative for this type of patients and should be studied in clinical trials. PMID- 1457534 TI - [Chronic manganese poisoning: autoradiographic quantification of cholinergic muscarinic receptors in mouse brain]. AB - Chronic administration of manganese chloride (5 mg Mn/kg body weight/day) during nine weeks, did not affect the [3H]-quinuclidinyl benzilate binding to muscarinic cholinergic receptors in mouse brain. The quantitation and anatomical distribution of the receptors were determined by autoradiographic methods on coronal sections of midbrain and olfactory bulb. It is concluded that, in our experimental conditions, no alteration in the density of the muscarinic cholinergic receptors is produced in the brain of manganese intoxicated mouse. PMID- 1457535 TI - [Teratogenic effect of the Venezuelan equine encephalitis virus: a review of the problem]. AB - Clinical findings on Venezuelan Equine Encephalitis virus infection and the teratogenic effects of several Togaviruses are described. Similarities between the intrauterine alterations induced by Venezuelan Equine Encephalitis virus and rubella virus are pointed out. Findings described by Wenger in 1967 were those of massive cerebral necrosis in fetuses of women presumably suffering of encephalitis and they are commented along with the development of an animal experimental model at the end of 1970-1980. Pathogenesis of the intrauterine infection seemed to be related to changes in the placental vessels, vascular changes in the central nervous system were also described in rats surviving Venezuelan Equine Encephalitis experimental infection; similar changes were described in the brain of children with post rubella syndrome. The need for multidisciplinary studies in the endemic areas of Venezuelan Equine Encephalitis in order to detect sequelae of the viral effects in utero is emphasized. Finally, some experimental animal models are proposed to examine diverse aspects on intrauterine effect of Venezuelan Equine Encephalitis virus. PMID- 1457536 TI - The use of computer-assisted diagnosis in cardiac-perfusion nuclear medicine studies: a review. AB - The use of computer-assisted diagnosis has become widespread in cardiac nuclear medicine. Quantitative programs are commercially available for ventriculography, phase analysis, and thallium 201 perfusion studies. The goal of these programs is to eliminate interobserver variability by objectively analyzing the studies without causing a loss of accuracy. In addition, by using quantitative data not apparent on visual inspection, some programs attempt to increase sensitivity for disease above that possible by the visual reading of images. Programs that analyze perfusion studies to detect coronary artery disease have received the most interest. Results have varied, but sensitivities as high as 95% have been reported. This review discusses the techniques of computer-assisted diagnosis for thallium 201 myocardial-perfusion studies. The circumferential and washout profile methods are discussed in detail. PMID- 1457538 TI - Cooperative image workstation based on explicit models of diagnostic information requirements. AB - A medical image workstation designed to act as a cooperative dialogue partner in diagnostic radiology has been conceived, and a prototype has been made. The system can automatically select relevant information (eg, from current and previous examinations) and generate a meaningful and appropriate image arrangement on the display screen. For a number of routinely performed tasks in radiology, the users' interaction may be as simple as switching from one patient to the next. This is shown to considerably simplify and speed up radiological image access and presentation, saving the user time and effort. The cooperative system response is based on explicit (formalized and computer-accessible) models of diagnostic information requirements. These models are context dependent and take into account that diagnostic information needs vary with radiological work procedures, workstation users, and patient cases. Initial models have been acquired from expert radiologists in two European hospitals and were integrated in a cooperative workstation prototype. For the representation of models, rule based and object-oriented techniques were applied. The rule base was designed with a distinct modular structure, separating between rule sets for general, task dependent, and user-dependent information requirements. The installed rule-based mechanism also offers a solution for the automatic prefetching of images to avoid transmission delays in the course of diagnostic work sessions. The first part of the report reviews the objectives for the design of cooperative workstation user interfaces and explains the benefits from the users' point of view. In the second part, the acquisition, structuring, formalization, and representation of context dependent information requirement models is described. The rule-based model is explained using examples. A layered workstation architecture consisting of model, object, and real-time layers is presented. Difficulties in the implementation of cooperative workstations are discussed that point to future research topics and standardization efforts. PMID- 1457537 TI - Enhancement of chest images by automatic adaptive spatial filtering. AB - Postprocessing of the image data is an exciting capability of digital radiography that may improve diagnostic performance. We present a new algorithm that selectively enhances edges and contrast in both lungs and mediastinum while minimally amplifying noise in chest images. Using different size kernels, two smoothed images are generated from the original chest image. The two regions of interest (lungs and mediastinum) are identified based on the distribution of pixel values in the image. A modified nonlinear unsharp mask subtraction technique is then applied. The resulting image has enhanced high- and middle frequency information in the mediastinum without distorting lung parenchyma or significantly enhancing noise. We consider that the technique employed in this study could be suitable for routine use although its true effectiveness in improving diagnostic accuracy awaits observer-performance evaluation that is currently under way. PMID- 1457539 TI - Three-dimensional display of hepatic venous anatomy generated from spiral computed tomography data: preliminary results. AB - A new method is presented for generating three-dimensional images of the hepatic venous anatomy from helical computed tomography (CT) scans using volumetric rendering. The helical CT scans were obtained using peripheral injection of intravenous contrast via a power injector. Five patients with suspected liver tumors were studied from which one sample case was selected for illustration. Surgical planning of hepatic resection from three-dimensional images will soon become a practical part of patient care. PMID- 1457540 TI - Demonstration of digital radiographs by means of ink jet-printed paper copies: pilot study. AB - Different digital medical images have been printed on paper with a continuous ink jet printer, and the quality has been evaluated. The emphasis has been on digital chest radiographs from a computed radiography system. The ink jet printing technique is described as well as the handling of the image data from image source to printer. Different versions of paper prints and viewing conditions were compared to find the optimum alternative. The evaluation has been performed to maximize the quality of the paper images to make them conform with the corresponding film prints and monitor images as much as possible. The continuous ink jet technique offers high-quality prints on paper at a considerably lower cost per copy compared with the cost of a film print. With a future switch-over from diagnosing of digital images on film to diagnosing them on monitors, hard copies for demonstration purposes will occasionally be needed. This need can be filled by ink jet-printed paper copies. PMID- 1457541 TI - Subsystem throughputs of a clinical picture archiving and communications system. AB - We measured the throughtput rates of individual picture archiving and communications system (PACS) subsystems including the acquisition, archive, display, and communication network as a basis of evaluation the overall throughput of our clinical PACS. The throughput rate of each PACS subsystem was measured in terms of average residence time of individual images in the subsystem. The residence time of an image in a PACS subsystem was determined by the total time the image was required to be processed within the subsystem. The overall throughput of the PACS was measured as the total residence time of an image in the various subsystems. We also measured throughputs of the PACS subsystems using three types of networks (Ethernet; fiber distributed data interface; and UltraNet, UltraNetwork Technologies, San Jose, CA), and the results were compared. Approximately 200 gigabytes of data transactions including magnetic resonance, computed tomography and computed radiography images from our PACS were analyzed. Results showed that PACS throughput was limited by three major factors: (1) low-speed data interface used in the radiologic imaging devices and archive devices; (2) competition for systems processing time among the PACS processes; and (3) network degradation caused by heavy network traffic. We concluded that PACS performance could be improved with a well-designed network architecture, a job prioritizing mechanism, and an image routing strategy. However, device-dependent low-speed data interface has limited PACS performance. PMID- 1457542 TI - Comparison of three different techniques for dual-energy subtraction imaging in digital radiography: a signal-to-noise analysis. AB - Dual-energy subtraction imaging techniques allow the tissue and bone structures in the patient to be visualized and studied in two separate images, thus removing the obscurity associated with overlapping of the two structures. In addition, they allow the subtraction image signals to be used for quantifying the tissue and bone thicknesses. Thus, capability for dual-energy subtraction imaging is often incorporated with new digital radiography systems. There are three different approaches to dual-energy image subtraction imaging techniques. Among them, the dual-kilovolt (peak) [kV(p)] and sandwich detector techniques have been two widely used approaches. A third approach is the single-kV(p) dual-filter technique, which allows some flexible control of the spectra while avoiding the technical complexity of kV(p) value switching in slit-scan imaging. In this report, the noise properties associated with these three techniques are studied and compared by computing the noise variances in the subtraction image signals as a function of the kV(p) values and filter thicknesses. It was found that the dual kVp technique results in the least noisy subtraction images, whereas the dual filter technique results in slightly less noisy subtraction images than the sandwich detector technique. Following optimization of the kV(p) value and filter thicknesses, the dual-filter and sandwich detector techniques result in a noise level of approximately three and four times higher than that resulted from the dual-kV(p) technique, respectively. PMID- 1457543 TI - Salmonella enteritidis in commercial layer farms in New York state; environmental survey results and significance of available monitoring tests. AB - Seven hundred fifty-one environmental samples were collected from 76 chicken layer houses in a voluntary Salmonella enteritidis (SE) survey study carried out in New York state between January 15 and April 8, 1991. SE was recovered from both houses on 1 farm. Sampling of manure pits and mice in hen houses was useful for SE screening. Phage types of SE from the environment, birds, and mice were identical. The rapid whole-blood test was unreliable, and culture of cloacal swabs was inadequate for detection of SE carriers. Culture of organs from chickens did not correlate well with results of environmental samples. PMID- 1457544 TI - Use of ELISA to detect toxigenic Pasteurella multocida in atrophic rhinitis in swine. AB - The use of an enzyme-linked immunosorbent assay (ELISA) as a means of detecting dermonecrotoxin-producing strains of Pasteurella multocida was investigated. The assay was evaluated as a means to identify toxigenic P. multocida isolates recovered from nasal secretions of swine with atrophic rhinitis. The sensitivity and specificity of the ELISA for detecting dermonecrotoxin-producing P. multocida strains were compared to those of mouse-inoculation and cytotoxicity assays. The ELISA was highly sensitive and more specific than animal inoculation or tissue culture assay and is thus a more effective method for screening swine herds for the presence of toxigenic strains of P. multocida. The ELISA is a rapid, effective, economical way to identify toxigenic P. multocida isolates. PMID- 1457545 TI - Mycobacterium bovis infection in North American elk (Cervus elaphus). AB - A naturally occurring outbreak of Mycobacterium bovis infection in captive wild elk (wapiti) in Montana was confirmed by mycobacteriologic examination. Twenty eight of 143 elk responded to M. bovis purified protein derivative (PPD) tuberculin injected intradermally in the cervical region (SCT). The results of comparative cervical tuberculin skin tests conducted within 9 days of SCT revealed greater responses to M. bovis PPD tuberculin than to M. avium PPD tuberculin in 23 of 28 elk responding. At necropsy, several grossly visible tuberculous lesions were observed in the parenchyma of the lung, thoracic lymph nodes, and submandibular lymph nodes. Microscopic examination of appropriately stained tissue sections revealed the presence of granulomatous lesions containing acid-fast bacilli. An enzyme-linked immunosorbent assay (ELISA) was developed using a sarkosyl extract of M. bovis (antigen) and peroxidase-labeled protein G (conjugate); reactions were detected in the sera of 8 of 9 elk responding to M. bovis PPD tuberculin. Lymphocyte blastogenic assay responses were detected using M. bovis antigens in 7 of 9 elk positive on skin tests using M. bovis PPD. PMID- 1457546 TI - Gross and microscopic lesions of naturally occurring tuberculosis in a captive herd of wapiti (Cervus elaphus nelsoni) in Colorado. AB - A Mycobacterium bovis-infected herd of captive wapiti (Cervus elaphus nelsoni) in Colorado was depopulated after lesions of bovine tuberculosis were confirmed in 8 of 10 tuberculin skin test reactors. Of the 43 animals > 1 year of age, 26 had gross lesions suggestive of tuberculosis, 24 had microscopic lesions of tuberculosis, and 23 had acid-fast bacilli associated with the lesions. Lungs and retropharyngeal lymph nodes were the most frequently affected sites. Most lesions grossly and microscopically resembled tuberculosis in cattle; however, some lesions resembled abscesses or ovine caseous lymphadenitis lesions. Special stains and immunohistochemical techniques labeled few to numerous mycobacteria associated with the lesions. PMID- 1457547 TI - Bovine plasma beta-mannosidase activity and its potential use for beta mannosidosis carrier detection. AB - Plasma beta-mannosidase activities were determined for Salers cattle from 8 herds as an evaluation of this method for detection of beta-mannosidosis heterozygotes. Several biological factors, such as age, gender, herd, and risk of being a beta mannosidosis carrier, were considered in this study. The mean enzyme activity for obligate heterozygotes (n = 8) was 55 U/ml (range = 43-65 U/ml), which was 59% of the mean enzyme activity for cattle that were low risk for being a carrier. These data indicate that bovine beta-mannosidosis is characterized by a gene dosage effect. The analytical and biological variation of plasma beta-mannosidase activity that was observed necessitates limiting the test to adult fullblood/purebred Salers cattle within a herd. Plasma beta-mannosidase analysis provides important information for intraherd selection of Salers cattle that are heterozygous for beta-mannosidosis. PMID- 1457548 TI - Confirmation of indandione rodenticide toxicoses by mass spectrometry/mass spectrometry. AB - Mass spectrometry/mass spectrometry (MS/MS) with collision-activated dissociation (CAD) was utilized to unequivocally distinguish 1,3-indandione rodenticides in 2 cases of anticoagulant toxicosis. Anecdotal evidence provided by the veterinarian in a case involving feedlot cows and physical evidence at the site of occurrence in a similar case involving lambs strongly implicated diphenadione (diphacinone; DP) in both instances. However, high performance liquid chromatography indicated chlorophacinone (CP), not DP, was present in the blood samples obtained from both cows and lambs. Intact 1,3-indandiones exhibit poor gas chromatographic properties, so procedures were developed for analysis by MS/MS using a direct exposure probe for sample introduction. The EI mass spectra of DP and CP contained a base peak at m/z 173, with molecular ions (M+) at m/z 340 and m/z 374 (Cl isotope cluster), respectively. Corresponding MS/MS CAD parent ion spectra of m/z 173 showed an ion of m/z 340 for DP and 374 (Cl cluster) for CP. CAD analysis of the blood extracts showed a parent ion scan of m/z 173 identical to that of CP, with the m/z 374 (Cl cluster). (Additional evidence was obtained by MS/MS examination of the CAD daughter ion spectrum of m/z 374.) Blood extracts from the affected animals revealed CAD daughter ion spectra for m/z 374 identical to that of reference CP. Positive confirmation of CP in both cases led to identification of the source of the toxicant and prevention of further animal exposures. PMID- 1457549 TI - Assessment of western immunoblotting for the confirmatory diagnosis of ovine scrapie and bovine spongiform encephalopathy (BSE). PMID- 1457550 TI - Budgerigar fledgling disease (papovavirus) in pet birds. PMID- 1457551 TI - A comparison of isolation and a commercial ELISA for the diagnosis of chlamydiosis in psittacine birds. PMID- 1457552 TI - Isolation of Chlamydia psittaci from pleural effusion in a dog. PMID- 1457553 TI - Development of a DNA hybridization probe for detection of Mycoplasma bovis. PMID- 1457554 TI - Strain diversity within bovine Pasteurella haemolytica serovar 2 respiratory tract isolates. PMID- 1457555 TI - Binding of a recombinant form of streptococcal protein G to porcine IgG. PMID- 1457556 TI - Diarrhea associated with Enterococcus durans in calves. PMID- 1457557 TI - Transmural intestinal penetration of polyester fibers as an uncommon cause of peritoneal adhesions in a dog. PMID- 1457558 TI - Peripheral neuroblastomas in two dogs. PMID- 1457559 TI - Outbreak of toxoplasmosis in wallabies on an exotic animal farm. PMID- 1457560 TI - Acute hepatic sarcocystosis in a chinchilla. PMID- 1457561 TI - Acute hepatic necrosis associated with a Sarcocystis-like protozoa in a sea lion (Zalophus californianus). PMID- 1457562 TI - Pulmonary coccidiosis in a dog. PMID- 1457563 TI - Lymphosarcoma in a desert bighorn sheep. PMID- 1457564 TI - The assessment of patients undergoing esophagectomy. PMID- 1457565 TI - Current status of preoperative treatment for carcinoma of the esophagus. PMID- 1457566 TI - Adenocarcinoma in Barrett's esophagus. PMID- 1457567 TI - Pectoralis major myocutaneous flap reconstruction of the laryngopharynx and cervical esophagus. PMID- 1457568 TI - Free jejunal interposition of the esophagus. PMID- 1457569 TI - Cervical exenteration. PMID- 1457570 TI - Comparison of transhiatal and transthoracic esophagogastrectomy. PMID- 1457571 TI - Transhiatal esophagectomy. AB - THE is a versatile procedure that has become indicated for a variety of disease processes over the past two decades; amongst these indications are to treat many benign and malignant esophageal diseases, as well as for use in restoring gastrointestinal continuity after extensive pharyngeal or laryngopharyngeal resections. Careful and meticulous handling, formation, and transposition of the gastric tube are essential to the development of a well-perfused neo-esophagus. Present studies indicate acceptable morbidity and mortality of THE compared with transthoracic resections for carcinoma of the esophagus. There appears to be no significant detriment in overall long-term survival when THE is used as primary resection therapy for malignant esophageal disease. PMID- 1457572 TI - Results of standard left thoracoabdominal esophagogastrectomy. AB - The left thoracoabdominal incision is approaching its first century of use. Although less popular than the Ivor Lewis and transhiatal techniques, it continues to be a useful approach for esophageal or gastric tumors near the gastroesophageal junction. For these tumors, the incision provides excellent exposure, and maximizes reconstructive options during esophagogastrectomy. The incision has a proven track record of safety and is well-tolerated. PMID- 1457573 TI - Ivor Lewis esophagectomy. PMID- 1457574 TI - Radical esophagectomy. PMID- 1457575 TI - Short segment colon and jejunal interposition. PMID- 1457576 TI - Long segment colon interposition. PMID- 1457577 TI - The BFM-protocol for HIV-negative Burkitt's lymphomas and L3 ALL in adult patients: a high chance for cure. AB - During a period of 9 years we used the pediatric BFM-NHL protocol for treatment of 14 adult patients with Burkitt's lymphoma or L3 acute lymphoblastic leukemia. Ten of 14 patients obtained a complete remission including 5/8 with stage-IV disease or B-ALL. After a median follow-up of 55 months none of these ten patients relapsed. The projected survival after 8 years is 71%. Toxicity was moderate, with one early death; a tumor lysis syndrome occurred in four patients. From our experience we conclude that the BFM-NHL protocol is very effective in adult patients, with a high cure rate and acceptable toxicity, even in advanced stages of disease. PMID- 1457578 TI - Increased risk of second cancers in managing Hodgkins disease: the 20-year Leiden experience. AB - Between January 1969 and December 1988, 482 patients were treated for Hodgkin's disease at the Leiden University Hospital. All cases were routinely recorded in the Hospital Information System, which has an active annual follow-up. Of all patients, 57% remained relapse free. According to the kinds of treatment they received, the following major categories were established: radiotherapy only (28.2%), chemotherapy only (20.1%), only initial combination of radiotherapy and chemotherapy (34.2%), all other combinations of radio- and chemotherapy (15.4%), or not registered (2.1%). Twenty-seven second cancers were observed; six leukemias, five non-Hodgkin lymphomas, and 16 solid tumors. Of all solid tumors only nine occurred in relapse-free patients. The overall relative risk of second cancers increased with the duration of follow-up. Using general population incidence rates to calculate expected numbers, the risk for developing leukemia, non-Hodgkin lymphoma, and solid tumors was increased 36-fold, 31-fold, and 2.4 fold, respectively. The cumulative risk of developing a second cancer 10 years after diagnosis of Hodgkin's disease was 7% for both the radiotherapy-only and the initial combination of radio- and chemotherapy group. It was 16% and 17% for the chemotherapy-only and the other combinations of radio- and chemotherapy group, respectively. Multivariate analysis (using the Cox regression model) show an increased risk of second cancers (RR = 0.7) when a relapse of Hodgkin's disease resulting in increasing cumulative therapy occurred. Age at diagnosis of Hodgkin's disease was an important determinant for the risk of non-Hodgkin lymphoma and solid tumors. Cumulative chemotherapy intensity was an important factor in increasing leukemic risk in a dose-response fashion. Apart from this, the stage of Hodgkin's disease, although closely related to the kind of therapy, seemed to have an independent effect on leukemic risk. PMID- 1457579 TI - Immune and hormonal changes in early-stage chronic lymphocytic leukemia patients. AB - Fifty-six previously untreated stage-I (according to Rai) chronic lymphocytic leukemia (CLL) patients were examined for their clinical data, immunological characteristics, and hormonal values. Dysfunction of T and B lymphocytes was demonstrated by changed lymphocyte blastogenic response to stimulation with phytohemagglutinin (PHA), concanavalin A (ConA), pisum sativatum agglutinin (PSA), wheat germ agglutinin (WGA), recombinant interleukin 2 (IL 2), and dextran sulfate (DxS); also by decreased immunoglobulin levels (IgG, IgA, IgE) and increased beta 2-microglobulin (beta 2-M) values. Simultaneously, dysregulation of the hypothalamic-pituitary-adrenal axis, immune system integration, imbalance of sex hormones, and changes in thyroid hormones were observed in the same group of patients. Disturbed immunohormonal interactions in early-stage CLL may be responsible for the pathogenetic mechanisms in this lymphoproliferative malignancy. PMID- 1457580 TI - No evidence for neoantigens in human plasma after photochemical virus inactivation. AB - Photodynamic virus inactivation of human fresh plasma mediated by visible light in the presence of the phenothiazine dyes methylene blue or toluidine blue was investigated to determine whether it influences functional, structural, and immunological properties of plasma proteins. The activities of the coagulation factors I, VIII, IX, X, and XI were affected to a certain degree, while those of most other plasma proteins were not. The elution profiles obtained by ion exchange chromatography of untreated and photodynamically treated plasma were almost identical. Using a number of antisera against human plasma and single plasma proteins, different immunochemical techniques revealed identical patterns for untreated and treated plasma. Thus, there was no indication that the photodynamic virus inactivation procedure applied considerably influences the properties of plasma proteins. PMID- 1457581 TI - Hemoglobin Kansas found in a patient with polycythemia. AB - A 62-year-old woman, long suspected of having heart disease, was admitted to our hospital for thorough examination. Her hemoglobin level was 17.7 g/dl and her 2.3 DPG level was 8.90 microM/ml RBC. The patient proved to have polycythemia, hemoglobin Kansas, and diabetes mellitus. To our knowledge, this is the third case of hemoglobin Kansas in the world. PMID- 1457582 TI - Treatment of neutropenia in Felty's syndrome with granulocyte-macrophage colony stimulating factor--hematological response accompanied by pulmonary complications with lethal outcome. AB - We report on a 67-year-old man with Felty's syndrome (FS) complicated by recurrent pneumonia and an infected wound, which was not healing in spite of maximal antibiotic and local therapy. Encouraged by previous experience, we treated him with granulocyte-macrophage colony-stimulating factor (GM-CSF). His total leukocyte count rose, but the patient's pneumonia deteriorated. In addition, a previously known chronic obstructive lung disease (COLD) was exacerbated acutely. These complications finally led to his death. Postmortem examination revealed widespread pneumonia with invasive aspergillosis and a peripheral adenocarcinoma in his left lung. PMID- 1457583 TI - Hemolytic-uremic syndrome associated with pancreatitis in an HIV-positive patient. AB - Hemolytic-uremic syndrome (HUS) is a newly recognized hematologic manifestation of HIV infection that may be triggered by local or systemic infections as well as by immunological disorders. We report the case of a 36-year-old HIV-positive man, an intravenous drug abuser who developed HUS during an episode of acute pancreatitis. Hematologic and clinical improvement occurred following 2 weeks of nonaggressive therapy including vitamin E and fresh-frozen plasma. PMID- 1457584 TI - Severe autoimmune hemolytic anemia in a patient with chronic lymphocytic leukemia responsive to fludarabine-based treatment. PMID- 1457585 TI - Hypoplastic acute leukemia: description of eight cases and search for hematopoietic inhibiting activity. AB - Hypoplastic acute leukemia (HAL) is characterized by pancytopenia and by hypocellularity of the bone marrow. The marrow contains equal to or more than 30% myeloblasts. Absence of tissue infiltrates and/or tumor masses is mandatory. Eight patients are described here. They do not fit into the FAB classification for either acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS), except for one patient who subsequently proved to have a chronic myelomonocytic leukemia (CMML). The median age is 65 years. Two patients, including the CMML patient, are alive, 22 and 6 months from diagnosis. Six patients have died. The median survival is 8 months. Normal bone marrow cells cultured either with HAL sera or with HAL peripheral blood mononuclear cells as feeders and exogenous GM-CSF yielded subnormal CFU-GM counts. This might indicate inhibitory activity of HAL serum and defective stimulatory activity of HAL peripheral blood mononuclear cells. PMID- 1457586 TI - Pharmacokinetics and hemostatic effect of different factor VIII/von Willebrand factor concentrates in von Willebrand's disease type III. AB - Four different plasma-derived concentrates composed of coagulation factor VIII (FVIII) and von Willebrand factor (vWF) of varying quality (Hemate-P, Behring; Profilate, Alpha; and F VIII-VHP-vWF, C.R.T.S Lille), or almost purified vWF (Facteur Willebrand, C.R.T.S Lille) and one recombinant F VIII concentrate (Recombinate, Baxter) were given, in doses of 30-60 IU VIII: C/kg or 70-110 IU RCof/kg, to five patients with von Willebrand's disease type III, in order to evaluate the role of the vWF in factor F VIII concentrates. All plasma concentrates except Profilate had a multimeric vWF pattern almost similar to that of normal plasma. Bleeding time (b.t.), VIII: C, vWF:Ag, ristocetin cofactor activity, and multimeric pattern of the plasma-vWF were followed for 72 h. Both Duke b.t. and the multimeric pattern in plasma normalized after infusion of Hemate-P, F VIII-VHP-vWF, and Facteur Willebrand and, to a lesser extent, after Profilate. As expected, in response to Recombinate there was no effect on primary hemostasis, and the half-life of F VIII procoagulant activity (VIII: C) was very short. Normalization of the vWF is important not only for improving the primary hemostasis, but also for maintaining the plasma F VIII concentration on a high level, both by reducing the elimination rate of infused F VIII and via a secondary release of endogenous F VIII. If a prompt hemostatic effect is required, we recommend a concentrate containing both F VIII and all vWF multimers, but for prophylactic treatment, pure vWF may be used. PMID- 1457587 TI - Effect of hypoxic exposure on iron absorption in heterozygous hypotransferrinaemic mice. AB - Heterozygous hypotransferrinaemic mice show serum iron, haemoglobin and reticulocyte levels similar to those of normal (+/+) controls but the plasma apotransferrin level is significantly reduced. Male heterozygous hypotransferrinaemic Balb/cJ mice and control (+/+) littermates were exposed to 1 3 days' hypoxia at 0.5 atmospheres. Controls increased their haemoglobin and iron absorption significantly during the first day of exposure; serum transferrin levels were increased and iron absorption had returned to normal levels by the third day or serum transferrin above normal levels and the elevated iron absorption persisted for longer than in controls. Serum iron levels were lower following hypoxic exposure than in controls. Liver iron loading was significantly enhanced by hypoxia in heterozygotes, but not in controls. These observations demonstrate the importance of the reservoir of plasma apotransferrin in the initial phase of enhanced erythropoiesis, and that the ability to enhance plasma levels of iron-bound transferrin is required in order to increase haemoglobin levels under the hypoxic stress. PMID- 1457588 TI - Iron stores and serum transferrin receptor levels during recombinant human erythropoietin treatment of anemia in rheumatoid arthritis. AB - Ten rheumatoid arthritis (RA) patients with anemia of chronic disorders (ACD) were treated with recombinant human erythropoietin (r-Hu-Epo) using a dose of 250 U/kg s.c. 3 times a week for 6 weeks, in order to evaluate its effects on the anemia, iron stores, and serum-soluble transferrin receptor (sTfR) levels. All patients showed a rise in hemoglobin (Hb). Median Hb increased from 5.9 (5.5-7.0) at baseline to 6.7 (5.8-7.8) at 3 weeks and to 7.2 (5.9-8.5) mmol/l at 6 weeks during treatment. Ferritin levels decreased significantly during the 6 weeks, and five patients were iron deficient after 6 weeks of treatment. TfR levels increased significantly at 3 and 6 weeks during treatment. These preliminary findings may indicate that r-Hu-Epo is effective in improving ACD in RA. The sTfR rise may be explained by an increase in erythroid precursor cell mass or increased TfR expression and a decrease in tissue iron stores, although direct effects of Epo on TfR regulation cannot be excluded. Large double-blind studies with r-Hu-Epo in patients with RA and ACD are warranted. PMID- 1457589 TI - Some storage characteristics of buffy coats used for preparation of platelet concentrates. AB - The present study examined biochemical storage lesions in 58 buffy coats (BCs) intended as the raw material for platelet concentrates. The work was conducted in three series; the aims were to investigate: (a) the storage quality of BCs obtained from the routine production (series I), (b) whether improvement in platelet quality could be achieved by continuous agitation during storage (series II), and (c) whether macroscopic aggregate formation indicates platelet damage (series III). Series I and II consisted of 20 BCs each. Series III compared ten BCs with visible clumping with eight BCs not demonstrating macroscopic aggregates. In series I and II platelet counts and platelet factor 4 (PF4) release were determined after 1, 3, 5, and 24 h; lactate dehydrogenase (LDH) extracellular activity was measured after 1 and 24 h. In addition, in series I elastase concentrations were analyzed after 3, 5, and 24 h. Finally, in series III extracellular beta-thromboglobulin (beta-TG) levels were determined after 18 24 h. Low platelet counts, most likely reflecting the presence of aggregate formation, were found in 20% of the BCs (series I); in this series a total of 25% demonstrated increasing platelet counts, together with elevated PF4 and elastase, over the study period. Significant biochemical storage lesions were found after 5 and 24 h of storage. The study also demonstrated that continuous agitation during storage does not improve platelet quality (series II) and that BCs demonstrating visible clumping (series III) had augmented levels of extracellular beta-TG (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457590 TI - A case of congenital leukemia with monosomy 7. AB - A case of congenital leukemia with monosomy 7 is reported. Immunological study of the blast cells using monoclonal antibodies was suggestive of both myelomegakaryocytic and T-lymphoblastic leukemia. Chromosomal analysis of the bone marrow cells showed monosomy 7. Chemotherapy was initiated with a combination of adriamycin, cytosine arabinoside, 6-mercaptopurine, and prednisolone. The patient obtained complete remission, which has been maintained for 4 years and 1 month. He receives no chemotherapy now. Our case shows that monosomy 7 in congenital leukemia is rare, but the presence of monosomy 7 in congenital leukemia does not necessarily indicate a poor prognosis. PMID- 1457591 TI - Kikuchi-Fujimoto disease complicated by severe rhabdomyolysis. PMID- 1457592 TI - [Effect of superlow doses (10(-18)-10-(-14) M) of biologically active substances: general rules, features, and possible mechanisms]. AB - The effects of ultra-low (10(-18)-10(-14) M) doses (ULD) of biologically active substances have been reviewed in terms of common regularities of ULD effects and peculiarities of action of various groups of compounds. The most common and at the same time paradoxical regularities of ULD action are bi- or polymodal patterns of dose dependence, absence or presence of an inverse effect at higher doses, and instability of ULD effect. Possible mechanisms of ULD action including the mechanism based on the adaptation theory are discussed. PMID- 1457593 TI - [Ganglioside lactones]. PMID- 1457594 TI - [An unusual leucine motif in amino acid sequences of subunit 9 of ATP-synthase from plant mitochondria, modified by mRNA editing]. AB - The amino acid sequences of subunit 9 of plant mitochondrial ATP-synthase contain a leucine motif which differs from the leucine repeat earlier detected within the composition of proteinaceous products of Myc, Fos, and Jun proto-oncogens. The structural organization of this repeat in proteolipid sequences can be modified via transformation of serine triplets into leucine ones as a result of editing of an appropriate mRNA. PMID- 1457595 TI - [Structural changes of chromatin during proto-oncogene activation by cycloheximide: dose-effect]. AB - The level of expression of cellular proto-oncogens c-myc and c-fos in rat liver has been studied as a function of protein synthesis rate (cycloheximide dose). Activation of proto-oncogens has been established to be initiated by 50% inhibition of nuclear protein synthesis. This promotes a certain level in chromatin structural rearrangements which is manifested, in particular, in decreasing activity of chromatin cleavage by Ca2+, Mg(2+)-DNAase and increasing degree of chromatin condensation. A role of topoisomerase II in chromatin structural rearrangements during proto-oncogen activation is postulated. PMID- 1457596 TI - [Membrane ATPase of Vibrio alginolyticus. Ion transport activity and homology with F0F1-ATPase from E. coli]. AB - F0F1-ATPase has been isolated from the marine alkali-resistant bacterium Vibrio alginolyticus. The enzyme subunits cross-reacted with antibodies against subunits alpha, beta, gamma, epsilon, and b of E. coli ATPase. The purified ATPase was reconstituted into liposomes effecting an ATP-dependent uptake of H+. Proton transport was inhibited by the ATPase blockers DCCD, triphenyltin, and venturicidin. Na+ ions had no effect on ATP-dependent proton transport. No ATP dependent transport of Na+ was detected in proteoliposomes. PMID- 1457597 TI - [Metabolism of extracellular phosphocreatine during changes in the ionic composition of the medium in the perfused rat heart]. AB - Perfusion of isolated rat hearts with a phosphocreatine (10(-4) M) containing solution to which strophanthin or KCl had been added up to a concentration of 27 mM as well as Ca2+ depletion decreased phosphocreatine concentration in the perfusate with a simultaneous increase in creatine and phosphocreatine concentrations in the myocardium. Neither high extracellular concentrations of Na+ (200 mM), nor phosphocreatine increased creatine and phosphocreatine levels in the myocardium. The effect of high sodium perfusion media was completely reversed by strophanthin. Phosphocreatine decreased the lactate content in the perfusate. Strophanthin or potassium chloride enhanced the effect of phosphocreatine on the lactate release. Conversely, creatine augmented the lactate content in the perfusate. A high specificity of the phosphocreatine effect on the myocardium independently of the ionic composition of the perfusate was postulated. A mechanism of protective effects of phosphocreatine and high sodium perfusion media on "calcium paradox" is proposed. PMID- 1457598 TI - [Significance of extracellular concentration of sodium ions in the protective effect during the "calcium paradox"]. AB - Increasing of extracellular sodium concentration up to 200 mM diminishes heart damage under "calcium paradox". Phosphocreatine (10(-4) M) potentiates the effect of high sodium perfusion media; in this case myoglobin release from the myocardium is minimal (5-9% of control). An the same time, ATP and phosphocreatine concentrations and oxidation to phosphorylation coupling in mitochondria remain at a sufficiently high level. Elevation of osmotic pressure by the effect of 120 mM sucrose enhances heart damage under "calcium paradox" both in the presence and absence of phosphocreatine. The protective effects of superhigh (200 mM) sodium concentrations and phosphocreatine are completely reversed by strophanthin or decreasing K+ concentration down to 0.5 mM. PMID- 1457599 TI - [Hydrocortisone and partial hepatectomy activate a proteinase associated with histones]. AB - Proteinase activity has been shown to be associated with histones of rat thymus and liver nuclei. Hydrocortisone increases the activity of proteinases associated with thymus nuclear histones. Increasing activity of histone-associated proteinases is also observed during intensive transcription and replication in regenerating rat liver. PMID- 1457600 TI - [Correlation between the stability of alpha-chymotrypsin at high temperatures and "salting in" of a strong solution]. AB - A correlation was found between the thermal stability of alpha-chymotrypsin and the coefficient Ks of the Sechenov equation as a quantitative measure of the "salting-in" or "salting-out" capacity of solutes. At high temperatures, an increase in the concentration of "salting-in" agents (KSNC, GuHCl, urea, formamide) resulted in thermal stabilization of alpha-chymotrypsin. The maximal (about 100-fold) stabilizing effect in concentrated solutions of salting-in agents was comparable with those induced by covalent modification with hydrophilic reagents or immobilization. Conversely, an increase in the concentration of "salting-out" agents stabilized the enzyme only marginally at high temperatures. An additivity of solutes' action on the thermal stability of the protein has been demonstrated. The observed correlation was explained in terms of the solutes' action on the reversible conformational transition of the enzyme native form into a much more stable form existing at high temperatures. PMID- 1457601 TI - [The effect of pyridine and pyridine-N-oxide on the monooxygenase system of rat liver microsomes]. AB - Effects of pyridine and pyridine-N-oxide on the monooxygenase system of rat liver microsomes have been studied. Pyridine (200 mg/kg) increased total cytochrome P 450 content and activated metabolism of some specific substrates 24 hours after injection. There was an increase in the degree of p-nitrophenol and chlorzoxazone hydroxylation due to increasing ethanol-induced cytochrome P-450IIE1 content. Pyridine was also able to induce cytochrome P-450IIB1 in rat microsomes; this reaction was accompanied by acceleration of 7-pentoxyresorufin 0-dealkylation. Cytochrome P-450IA1 appearance in liver microsomes was associated with increasing content of cytochrome P-450IA2. Dealkylation rates for specific substrates (7 ethoxyresorufin and 7-methoxyresorufin) were also increased. Similar to pyridine, pyridine-7-oxide induced cytochromes P-450IIE1, P-450IIB1/B2, and P-450IA1/A2, resulting in activation of specific substrate metabolism. Hence, pyridine and its derivative pyridine-N-oxide can be regarded as effective inducers of cytochrome P 450. PMID- 1457602 TI - [Membrane transport of antigenic peptides]. PMID- 1457603 TI - Cell death induced by vincristine in the intestinal crypts of mice and in a human Burkitt's lymphoma cell line. AB - Although vincristine is widely used clinically in the treatment of some human cancers, its mechanism of action has not been clearly established. In this study, the patterns of cell death induced by vincristine in the intestinal crypts of mice and in a human Burkitt's lymphoma cell line were investigated by light and electron microscopy. Vincristine was found to enhance apoptosis of interphase cells in both systems and also to cause the arrest of cells in mitosis, the latter effect being more pronounced in the intestinal crypts. Arrested mitotic cells went on to die by a process that had a number of features in common with apoptosis. These include compaction of chromatin (following coalescence of chromosomes), condensation of the cytoplasm, initial preservation of organelle integrity, and eventually the fragmentation of the cell into a number of membrane enclosed bodies which are morphologically similar to conventional apoptotic bodies. The results suggest that the cytocidal effect of vincristine is not solely dependent on metaphase arrest but is a cumulative one, resulting both from apoptosis of interphase cells and the 'apoptotic-like' death of cells arrested in metaphase. PMID- 1457604 TI - The role of cell death in the growth of preneoplastic lesions: a Monte Carlo simulation model. AB - A variety of experimental and clinical examples of preneoplasia demonstrate that regression of early lesions is common. This paper examines the hypothesis that early lesions operate under the identical growth kinetics of 'late' lesions (neoplasms), but that kinetic features favouring continuous growth in established lesions tend to favour extinction of lesions composed of small numbers of cells. Growth simulations of early lesions were produced using the Monte Carlo method, a technique demanding intensive computations. With the advent of powerful personal computers, this technique is now widely available to biologists. Simulating growth under conditions of cell loss similar to those observed in established tumours, the model predicts that the great majority of initiated cell clusters are expected to reach extinction within a few cell doubling times, and most early (promoted) lesions would not likely progress to the size of a clinically detectable lesion within the life span of the host organism. These Monte Carlo simulations provide a model of initiated cell growth consistent with the recently demonstrated role of early lesion cell death in the development of human lymphomas and in transgenic mice expressing the bcl-2 oncogene. The model demonstrates that small increments in the intrinsic cell loss probability in even the earliest progenitors of malignancy can strongly influence the subsequent development of neoplasia from initiated foci. PMID- 1457605 TI - A model of the control of cellular regeneration in the intestinal crypt after perturbation based solely on local stem cell regulation. AB - The control mechanisms involved in regeneration of murine intestinal crypts after perturbations are presently not well understood. The existence of some feedback signals from the cells on the villus to the cells in the crypt has been suggested. However, some recent experimental data point to the fact that regeneration in the crypt starts very early after perturbation, at a time when the villus cell population has hardly changed. In particular, this early cell proliferative activity is seen specifically at the bottom of the crypt, i.e. in the presumed stem cell zone and furthest from the villus. The objective of this study was to investigate whether a new concept of regulation operating solely at the stem cell level could explain the present mass of accumulated data on the post-irradiation recovery, which is an extensively studied perturbation from the experimental point of view. In order to check its validity, the new concept was formalized as a mathematical simulation model thus enabling comparison with experimental data. The model describes the cellular development from stem cells to the mature villus cells. As a basic feature it is assumed that the self maintenance and the cell cycle activity of the stem cells are controlled by the number of these cells in an autoregulatory fashion. The essential features of the experimental data (i.e. the recovery with time and the consistency between different types of measurements) can be very well reproduced by simulations using a range of model parameters. Thus, we conclude that stem cell autoregulation is a valid concept which could replace the villus crypt feedback concept in explaining the early changes after irradiation when the damage primarily affects the crypt. The question of the detailed nature of the control process requires further investigation. PMID- 1457606 TI - Ferritin-iron increases killing of Chinese hamster ovary cells by X-irradiation. AB - Stationary-phase Chinese hamster ovary cells were cultured in medium containing ferritin (approximately 19% iron by weight) added at concentrations ranging from 0 to 128 micrograms/ml. One set of cultures was unirradiated, and another set was exposed to 4.0 Gy of X-ray. Clonogenic cell survival was assessed in each set of cultures. In the absence of added ferritin, 4.0 Gy killed approximately 50% of the cells. In the absence of radiation, ferritin was not toxic at less than 48 micrograms/ml; above 48 micrograms/ml, toxicity increased with concentration. Apoferritin was not toxic at any concentration tested (up to 1000 micrograms/ml). Although 32 micrograms/ml ferritin, reflecting only a 3-6 fold increase in iron concentration over normal serum, was not toxic, it reduced the survival of X irradiated cells by an additional 75%. These results indicate that a sublethal concentration of ferritin can be a potent radiosensitizer. This suggests the possibility that high body iron stores may increase susceptibility to radiation injury in humans. PMID- 1457607 TI - Haemopoietic long-term bone marrow cultures from adult mice show osteogenic capacity in vitro on 3-dimensional collagen sponges. AB - Adult murine bone marrow cells, cultured under conditions for long-term haemopoietic marrow cultures, produce bone matrix proteins and mineralized tissue in vitro, but only after the adherent stromal cells were loaded on a 3 dimensional collagen sponge. Provided more than 8 x 10(6) cells are loaded, mineralization as measured by 85Sr uptake from the culture medium, occurred in this 3-dimensional configuration (3-D) within 6 days. In contrast if undisrupted marrow fragments (containing more than 10(7) cells) are placed directly on a collagen sponge, then it requires more than 10 days before significant mineralization can similarly be detected. The 2-dimensional (2-D) long-term marrow culture system allows prior expansion of the stromal cells and some differentiation in an osteogenic direction within the adherent stromal layer. This is suggested by the presence of type I collagen and alkaline phosphatase positive cells. However; synthesis of osteonectin and a bone specific protein, osteocalcin, as well as calcification are only observed in 3-D cultures. Electron microscopy demonstrated hydroxyapatite mineral on collagen fibres, osteoblast like cells, fibroblasts, cells which accumulated lipids, and macrophages which were retained on the collagen matrices. Irradiation of confluent long-term bone marrow cultures, prior to their loading on the collagen sponge showed that haemopoietic stem cells are not necessary for the mineralization. PMID- 1457608 TI - Autoradiographic studies of rat astroglial cell proliferation in vitro with and without treatment with basic fibroblast growth factor. AB - Using specific autoradiographic methods, cell cycle parameters of untreated and basic fibroblast growth factor (bFGF)-treated astroglial cells from newborn rats grown in primary culture were directly measured. The mode of proliferation was also analysed. In untreated cultures, S phase duration (Ts = 6.9-13.1 h) and cell cycle time (Tc = 10-18 h) can be modified by about a factor of 2 depending on the culture conditions (serum-supplemented or defined medium, thyroid hormone concentration). However, growth fraction (GF = 0.15) and the ratio Ts/Tc remain stable. With increasing days in vitro (DIV) (DIV 7-DIV 20), Ts (7.8-10.6 h) and Tc (10-21 h) are prolonged and GF (0.14-0.06) decreases, probably due to cell maturation. In general, astroglial cells proliferate exponentially with a GF < 1, but stop proliferating about 30-36 h after the last feeding, probably caused by exhaustion of the medium. However, after refeeding they continue to proliferate. As opposed to in vivo, no transition of non-proliferating cells into the GF occurs. After addition of bFGF, GF increases (e.g. GF at DIV 7 = 0.43), but Ts and Tc are not influenced at DIV 7 and 12. At DIV 20, bFGF additionally shortens Ts and Tc, thereby producing values of Ts, Tc and GF like 'younger' cultures. However, the revitalizing effect on 'mature' cells is only transitory. In general, bFGF leads to a single re-entry of G0 cells into the GF. Thereafter, bFGF does not affect the mode of proliferation. PMID- 1457609 TI - The mechanism of action of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in the control of haematopoietic stem cell proliferation. AB - The mechanism of action of the haemoregulatory tetrapeptide Acetyl-N-Ser-Asp-Lys Pro (AcSDKP, M(r) = 487 amu), was investigated using an in vitro assay of a murine high proliferative potential colony-forming cell (HPP-CFC) which responds to proliferation regulators of the haematopoietic stem cell population. AcSDKP had no direct inhibitory effect on the number, or the proportion in S phase, of the committed granulocyte-macrophage progenitor (GM-CFC), or cycling HPP-CFC populations. However, AcSDKP blocked the action of a stimulator of haematopoietic stem cell proliferation, preventing the switching of quiescent HPP-CFC into cell cycle. It would appear that AcSDKP exerts its inhibitory haemoregulatory role indirectly, by preventing stimulator action on haematopoietic stem cells. PMID- 1457610 TI - Effects of growth media on cell cycle progression in CHO cells exposed to the radioprotector WR-1065. AB - WR-1065 (2-[(aminopropyl)amino]ethanethiol) reduces cytotoxic and mutagenic effects caused by exposure of cells to radiation and chemotherapeutic drugs, but the mechanisms involved are not fully known. We have observed an accumulation of cells in G2 in WR-1065 treated Chinese hamster ovary cells grown in alpha-minimal essential medium, while others have found no cell cycle effects in WR-1065 treated Chinese hamster ovary cells grown in McCoy's 5A medium. To determine if the two types of media had an effect on cells treated with WR-1065, we examined survival and cell cycle progression. Population doubling times of 12 h were observed for cells grown in both media. Incubation of AA8 cells grown in McCoy's 5A medium with 4 mM WR-1065 30 min prior to and during irradiation with 137Cs gamma-rays resulted in a protection factor of 2.2, in close agreement with the value of 2.0 we previously obtained for AA8 cells grown in alpha-minimal essential medium. Treatment with WR-1065 caused an alteration in the cell cycles of cells grown in both media. An increase in the G2 population and a decrease in the G1 population was observed in cells incubated up to 3 h in the presence of 4 mM WR-1065, with a redistribution of the cells throughout the cell cycle occurring following removal of the drug. These data suggest that exposure of cells to WR-1065 is the cause of perturbations in cell cycle progression, and is not affected by the type of medium the cells are grown in. PMID- 1457611 TI - Comparison and characterization of retinal pericytes and retinal pigment epithelial cells on subcellular IP3-sensitive Ca2+ pools. AB - A comparative study of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ mobilization in bovine retinal capillary pericytes (BRCP) and bovine retinal pigment epithelial cells (BRPE) was carried out. Both cells were permeabilized with saponin. The two cell types had similar basal levels of [Ca2+]i (130 nM for BRCP, 132 nM for BRPE) and responded to IP3 in a dose-dependent manner. However, when stimulated by various concentrations of IP3 (1-10 microM), the increase in [Ca2+]i of BRCP was always two- to threefold higher than that in BRPE. Subcellular-fractionation studies showed that a single population of IP3 binding site with a high affinity and high specificity of IP3 mainly localized to plasma membrane in these two cell types. Although the dissociation constant of specific [32P]-IP3 binding sites (Kd 1.9-2.8 nM) was similar, the profile of maximal binding capacity (Bmax) of each fraction was markedly different. In comparison, plasma membrane fractions of BRCP were with Bmax of 165 fmol/mg protein versus 90 fmol/mg protein for BRPE membranes. The ATP-dependent Ca2+ uptake and IP3 dependent Ca2+ release were observed in the both plasma membrane fractions. With quantitative correlation, the membrane fraction (2 mg) of BRCP released 0.2 nmol Ca2+ whereas BRPE only released 0.07 nmol Ca2+ with the same dose of IP3 (5 microM). The selectively higher density of IP3 binding sites in coupling to the larger Ca(2+)-release in the membrane of BRCP suggests that the quantity of Ca2+ mobilized is determined by the spatially preferential distribution of membrane associated IP3 binding sites. These findings may provide an explanation for the differences observed between BRCP and BRPE in IP3-induced DNA replication. PMID- 1457612 TI - The relationship of chemical modification of membrane proteins and plasma lipoproteins to reduced membrane fluidity of erythrocytes from diabetic subjects. AB - The significance of the two most common hallmarks of the diabetic state, hyperglycaemia and hyperlipidaemia, was investigated in terms of disorders of cell membrane dynamics. In order to examine whether the alterations in cell membrane lipid bilayer dynamics are somehow related to protein chemical modifications in plasma low-(LDL) and high-density lipoproteins (HDL) and blood cell membranes, we compared 19 poorly controlled diabetic subjects with 19 age- and sex-matched controls. The extent of (non-enzymatic) glycation, lipid peroxidation and the cholesterol/phospholipid ratio were increased in plasma low density lipoproteins and high density lipoproteins from diabetic patients. The mean steady-state fluorescence polarization values in 1,6-diphenyl-1,3,5 hexatriene-labelled isolated erythrocyte membranes from diabetic subjects were significantly greater than from control subjects (0.186 +/- 0.008 vs 0.173 +/- 0.006, p < 0.001); the fluorescence polarization values in erythrocyte membranes from diabetic and control subjects positively correlated with the extent of membrane protein glycation, lipid peroxidation and the cholesterol content. The cholesterol to phospholipid molar ratios in low density lipoproteins and high density lipoproteins from diabetic and control subjects correlated significantly with the fluorescence polarization values in erythrocyte membranes from these subjects. Furthermore, the extent of glycation of low density lipoproteins appears to be strongly correlated with the extent of lipoprotein lipid peroxidation (r = 0.789, p < 0.001). The atherosclerotic potential of plasma lipoproteins in diabetes mellitus was discussed in terms of membrane and plasma protein chemical modifications. PMID- 1457613 TI - Determination of 2'-5'-oligoadenylate synthetase in serum and peripheral blood mononuclear cells before and after subcutaneous application of recombinant interferon beta and gamma. AB - The interferon-inducible enzyme, 2'-5'-oligoadenylate synthetase, was estimated in healthy donors and in patients before and after subcutaneous application of recombinant interferon beta and gamma. Tests were carried out with lysates of peripheral blood mononuclear cells, using an established radioenzymatic assay, and in serum samples, using a new radioimmunoassay. Both test systems substantially yielded the same results: after a single injection of interferon beta (1-5 x 10(6) IU), 2'-5'-oligoadenylate synthetase increased in a dose dependent manner reaching maximal catalytic concentrations in most patients after 24-48 hours (leukocytes) and 48-72 hours (serum). In contrast, interferon gamma (2-4 x 10(6) IU) caused only a small induction of 2'-5'-oligoadenylate synthetase. However, daily application of interferon gamma for 7 days led to a distinct time-dependent increase of 2'-5'-oligoadenylate synthetase activity concentration during this observation period. Characteristically, even during daily application, the 2'-5'-oligoadenylate synthetase activity concentration dropped just 48-72 hours after the first injection of interferon beta. The determination of 2'-5'-oligoadenylate synthetase proved to be useful for optimizing and monitoring subcutaneous therapy with interferon. The new radioimmunoassay which allows the determination of this enzyme in serum is superior to other methods used in the past. PMID- 1457614 TI - Affinity of europium-labelled proteins A and G for immunoglobulin G from seven mammalian species. AB - Proteins A and G were each labelled with two different europium chelates (p isothiocyanatophenyl-ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid). Their affinities for IgG from rabbit, goat, horse, sheep, mouse, pig, and rat were then measured using time-resolved fluorescence. Protein G labelled with the second chelate was found to be especially effective in binding to goat and horse IgG. PMID- 1457615 TI - A fully automated enzyme immunoassay for the measurement of cortisol in biological fluids. AB - This paper describes a fully automated assay on the Serono SR1 for the measurement of cortisol in serum, heparinised plasma and urine. The assay incorporates a specific polyclonal antibody to cortisol and cortisol conjugated to alkaline phosphatase as a label. Following immunoincubation, bound and free labelled cortisol are separated by magnetic sedimentation of the antibody complex. Phenolphthalein is liberated by the enzymatic hydrolysis of the substrate (phenolphthalein monophosphate) and the absorbance generated is measured as the assay end-point. All processing steps are performed by the SR1. The assay has good analytical performance with respect to precision (within and between run CVs less than 10 and 11.5% respectively), detection limit (less than 5 nmol/l) and recovery of added cortisol (100 +/- 10%). The assay agrees well with cortisol concentrations determined by ID-MS and by established immunoassays (r > 0.96). Reference ranges of normal urine samples (pretreated by solvent extraction) are in good agreement with accepted values. The study demonstrates that the SR1 Cortisol assay on the SR1 analyzer is suitable for the routine determination of cortisol in serum, heparinised plasma and urine samples. PMID- 1457616 TI - Which is the appropriate coenzyme for the measurement of ammonia with glutamate dehydrogenase? AB - The determination of ammonia in plasma, using glutamate dehydrogenase, is complicated by non-specific oxidation of the coenzyme, promoted by components of the sample matrix. Measurements performed with appropriate plasma blanks show that 2'-phosphorylated coenzymes (NADPH, deamino-NADPH) are much less oxidized than NADH. By adding lactate dehydrogenase, NADH oxidation by endogenous pyruvate can be completed within a short time. Considerable consumption of coenzyme occurs, however, and endogenous L-alanine aminotransferase also represents a possible source of interference. The results of ammonia determinations using deamino-NADPH (y) or NADPH (x) were identical (a = 0.0 mumol/l, b = 1.00; r = 0.996, n = 62). With NADH as the coenzyme, the method displays adequate specificity only at high sample dilution, e.g. in the measurement of urea after conversion to ammonia. PMID- 1457617 TI - Free epinephrine, norepinephrine and dopamine in saliva and plasma of healthy adults. AB - To investigate whether salivary catecholamine levels reflect short term changes of sympathoadrenal activity, we simultaneously measured plasma and saliva epinephrine, norepinephrine and dopamine concentrations at rest, during bicycle ergometry and during epinephrine infusion in 12 healthy adults, using a radioenzymatic method. Whereas all plasma catecholamines significantly increased during bicycle ergometry and epinephrine infusion, no changes were observed in the salivary catecholamine concentrations and the salivary catecholamine flow rate after stimulation by rhythmic chewing. Moreover, salivary catecholamine concentrations were related neither to heart rate nor to blood pressure. Obviously, free catecholamines are rapidly inactivated by enzymatic degradation, neuronal reuptake or extraneuronal uptake in tissues before they diffuse through the tight junctions into the saliva. Therefore, stimulated saliva catecholamine levels do not reflect short term changes in the activity of the sympathoadrenal nervous system. PMID- 1457618 TI - Influence of reagent composition on atypical pseudocholinesterase activity measurement: comparison of a manual and an automated method and implications for routine. AB - In determining activities of atypical pseudocholinesterase using a Hitachi 737 and a Cobas Bio analyser, respectively, we repeatedly found discrepancies between the enzyme activities measured by both instruments which were presumably due to differences in the reagent composition (Hitachi 737: Boehringer Mannheim Automated Analysis for BM/Hitachi Systems; Cobas Bio: Boehringer Mannheim Monotest). We consider the present results as a strong hint for manufacturers towards generally declaring all components of the chemical systems they produce and as a warning for users when interchanging apparently identically composed sets of reagents. PMID- 1457619 TI - A multicentre evaluation of the Ektachem DT60-, Reflotron- and Seralyzer III systems. AB - The analytical performance of the three analytical systems Reflotron, Ektachem DT60 and Seralyzer III was studied according to ECCLS guidelines (1) and partly according to a protocol of the Societe Francaise de Biologie Clinique (SFBC) (2) in a multicentre evaluation involving four laboratories. The determination of 11 analytes led to more than 180,000 data. With the Ektachem DT60, imprecision was acceptable for all analytes except for sodium. With the Reflotron, imprecision for glucose and creatinine was wider than the acceptable limits. With the Seralyzer III, imprecision for glucose, uric acid, cholesterol, creatinine and potassium was not within acceptance limits. The recovery of system assigned control sera values was acceptable for all analytes, except for glucose, creatinine and sodium with the Ektachem DT60 system, and for all but glucose and cholesterol with the Reflotron. On the Seralyzer III, the limits of acceptance were exceeded only with the creatinine assay. The recovery of the reference method values with Kontrollogen L caused problems with all three systems and for all analytes. Only 30% of the mean values of Kontrollogen L measured with the Ektachem and with the Seralyzer III were within the limits of acceptance. 40% of the mean values determined with the Reflotron were inside these limits. The upper limits of linearity as claimed by the manufacturers were obtained with all analytes and systems with the exception of cholesterol on all systems and the creatinine assay on the Seralyzer III. The systems under test and several different comparison methods showed good agreement for the analysis of patient samples, except in one laboratory for the analysis of sodium and aspartate aminotransferase with the Ektachem system and potassium with the Seralyzer III. Turbidity showed no significant influence on the measurements of all analytes and all systems. Haemolysis, hyperproteinaemia, and bilirubinaemia affected several methods on all three systems. A start time delay of up to 60 s did not affect the results of the Reflotron, except in the case of the triacylglycerol assay, which was affected by start time delays greater than 45 s. The results of 4 assays on the Seralyzer III were decreased considerably by a delayed start time (triacylglycerols and creatinine above 5 s, aspartate aminotransferase above 35 s and creatine kinase above 15 s). For reliable results from all the assays in each of the three analytical systems, it was necessary to use the prescribed sample volume within certain limits. The practicability of all analytical systems tested was found to be very good. A field study was conducted with the Reflotron system. The analyte concentration was determined in venous blood from various patients. In 25 out of 30 experiments, the results of the "field" laboratories showed a greater spread about the fitting line than those obtained in the "expert" laboratories. PMID- 1457620 TI - Event-related potential correlates of impaired selective attention in children at high risk for schizophrenia. AB - Auditory event-related potentials (ERPs) associated with selective attention were recorded in 21 children at high-risk for schizophrenia and in 21 matched controls. The subjects performed a selective listening task. For behavioral evaluation, target counts on the selective listening task and on cognitive performance were assessed. Group-specific differences of ERP components could be demonstrated, as reflected by significant amplitude reductions of the frontally located negative difference wave (Nd) and of the P3 component, following selectively attended stimuli, in the high-risk children. P3 latencies tended to be prolonged in the high-risk group. Reduced Nd was found in 14 and reduced P3 in 16 high-risk children among the 21 matched pairs. Significant correlations between the ERP reductions and psychometric deficit (counting accuracy) were observed. Mismatch negativity (MMN), an ERP component associated with automatic processing of physically deviant stimuli, did not differentiate significantly between groups, but was distinctly reduced in the high-risk group. The Nd and P3 reductions suggest deficits of selective attention in a considerable number of the subjects genetically at risk for schizophrenia. The present findings are discussed with respect to their relevance as indicators of a predisposition to schizophrenia. PMID- 1457621 TI - Periodicity of episode occurrences in rapid cycling affective disorders. AB - We analyzed the medical records of nine patients with severe rapid cycling affective disorders (RCAD), and determined the cycle of mania occurrences by calculating the period between two successive onsets of mania for each patient. Using the cycle as the index we devised a cycle-oriented diagram by dividing the observation period by the index cycle, and visually studied the mode of episode occurrences. In seven patients, the onset of mania generally followed the index cycle, but sometimes shifted from the day estimated by the index cycle. The shift seemed to be caused by a cycle other than the index cycle, which appeared temporarily in the course. The period between two successive onsets of mania was often several times longer than the index cycle length. In patients with RCAD, some sort of periodic rhythms may possibly control the course of episode occurrences on a continuing basis. PMID- 1457622 TI - EEG mapping and psychopharmacological studies with denbufylline in SDAT and MID. AB - Computed tomography (CT), electroencephalograms (EEG), clinical and psychometric data were obtained in 96 mildly to moderately demented patients (72 women, 24 men), aged 61-96 years (mean 82), diagnosed according to DSM-III criteria. Patients were off drugs for at least 2 weeks and subdiagnosed according to the modified Marshall-Hachinski ischemic score and CT in 45 senile dementia of the Alzheimer type (SDAT) and 51 multiinfarct dementia (MID) patients. Evaluations were carried out before and 12 weeks after treatment with either 100 mg denbufylline BID or placebo and included EEG mapping, the Sandoz Clinical Assessment Geriatric (SCAG) score/factors, the Clinical Global Impression (CGI), the Digit Symbol Substitution Test (DSST), the Trail-Making Test (TMT) and the Digit Span Test (DS). Descriptive data analysis including confirmatory statements found delta/theta activity enhanced, alpha and beta activity reduced, total power augmented, and the centroid slowed down over various brain regions in patients as compared with controls. The two subtypes of dementia could be differentiated in some conventional EEG variables but mostly by means of power asymmetry indices. Denbufylline induced a statistically significant and clinically relevant improvement in both SDAT and MID patients, whereas after placebo this was not the case in CGI, the TMT, and the DS, with interdrug differences being significant in all primary target variables such as the CGI, MMS, SCAG, and DSST. Thus, both the degenerative and vascular type of dementia exhibited a therapeutic benefit that could be objectified at the neurophysiological level by EEG mapping in an improvement of vigilance. PMID- 1457623 TI - Brainstem auditory evoked responses (BAERs) during the menstrual cycle in women with and without premenstrual syndrome. AB - Brainstem auditory evoked responses (BAERs) were recorded at three menstrual cycle phases (menstrual, late follicular, and late luteal) in a sample of healthy control women (n = 21) and in a sample of women (n = 30) diagnosed as suffering from Late Luteal Phase Dysphoric Disorder (LLPDD). The latter were divided on the basis of retrospective and prospective self-ratings into moderate (PMS+) and severe (PMS++) symptom groups. Results showed (1) no change in BAER latencies at different phases of the menstrual cycle; (2) increased BAER latencies for wave III in women with moderate PMS symptoms compared with healthy controls; (3) increased BAER latencies for waves III and V in women with severe PMS symptoms compared with healthy controls. These results raise the possibility of brainstem dysfunction in PMS women, and support the idea of a neurobiological predisposition to this order. PMID- 1457624 TI - Blood flow response to auditory stimulations in normal, mentally retarded, and autistic children: a preliminary transcranial Doppler ultrasonographic study of the middle cerebral arteries. AB - Using the noninvasive transcranial ultrasonic Doppler method, flow dynamics of the middle cerebral arteries were investigated in relation to auditory stimulations in 12 children with autistic behavior compared with 12 normal controls and 10 mentally retarded children. In normal children, auditory stimulation evoked lateralized modifications: blood flow increased and resistance index decreased on the left side; such modifications were not recorded on the right side. This pattern should indicate vasodilatation mechanisms induced by changes in the metabolism of the brain areas supplied by the left middle cerebral arteries (MCA). Although less asymmetrical, this pattern was also found in the mentally retarded children. Autistic children significantly differed from these two groups. They displayed a symmetric pattern of responses with a blood flow decrease and resistance-index increase on both sides; this could suggest abnormal metabolic mechanisms induced by auditory stimulation in autistic children and could be related to the previous hypothesis of impairment in the development of cerebral lateralization in autism. These preliminary results show that transcranial Doppler ultrasonography may be a valuable and practicable tool for the noninvasive study of evoked blood flow responses in psychopathology. PMID- 1457625 TI - Changes in norepinephrine output following light therapy for fall/winter seasonal depression. AB - Recurrent fall/winter depressions that remit during spring and summer have been called Seasonal Affective Disorders (SAD) (Wehr and Rosenthal 1989). The pathophysiology of SAD, its relationship to nonseasonal affective disorders, and the mechanism of action of light therapy, which is effective in treating SAD, remain to be elucidated (Depue et al 1989; Jacobsen et al 1987; James et al 1986; Joseph-Vanderpool et al 1991; Skwerer et al 1988, Terman et al 1989). Norepinephrine (NE) may play a role in the mechanisms of action of many antidepressant treatments (Schildkraut 1965) that alter NE metabolism (Schildkraut et al 1964 and 1965) and decrease the urinary output of NE and its metabolites, i.e., "whole-body NE turnover" (WBNET) (Golden et al 1988; Potter et al 1988). The present study explored whether light therapy also reduces the urinary output of NE and its metabolites. PMID- 1457626 TI - Melatonin and jet lag: confirmatory result using a simplified protocol. AB - This study replicates the alleviation of jet-lag with melatonin in a simplified protocol for eastward flight. At 22-n hr (n is the time-lag between the North American departure point and France), subjects took either melatonin (8 mg, n = 15), or placebo (n = 15) on the day of the return flight and for 3 consecutive days. On day 8, self-ratings significantly discriminated between melatonin and placebo for global treatment efficacy, morning fatigue, and evening sleepiness. PMID- 1457627 TI - The use of carbamazepine for episodic violence in multiple personality disorder and dissociative disorder not otherwise specified: two additional cases. PMID- 1457628 TI - Ganglioside antibodies in schizophrenia and major depression. PMID- 1457629 TI - Thrombin-induced platelet calcium mobilization is enhanced in bipolar disorders. PMID- 1457630 TI - Antinuclear and gastric parietal cell autoantibodies in schizophrenic patients. PMID- 1457631 TI - Evolving role of flucytosine in immunocompromised patients: new insights into safety, pharmacokinetics, and antifungal therapy. AB - Flucytosine is an antifungal agent useful in combination with amphotericin B in the treatment of several deeply invasive mycoses. The potentially dose-limiting, hematologic, gastrointestinal, and hepatic toxicities of flucytosine lead to a reluctance to use it in myelosuppressed patients. To investigate the safety and tolerability of flucytosine in this setting, we evaluated its use in 17 patients with cancer or aplastic anemia during a 2 1/2-year period at our institution and reviewed the literature describing mechanisms of action, resistance, in vitro and in vivo antifungal activity, clinical antifungal activity, pharmacokinetics, and toxicity. The combination of amphotericin B plus flucytosine eradicated the mycosis in 12 (71%) of 17 patients, whereas 3 (18%) of 17 died of progressive fungal infection. Serial serum levels of flucytosine measured by a creatinine iminohydrolase assay permitted reliable dosage adjustment. During therapy, only 2 (12%) of 17 patients had elevated mean serum levels of flucytosine (> 100 micrograms/mL) and 3 (18%) other patients had transiently elevated levels. Paired serum samples (n = 45) obtained at steady state during therapy with orally administered flucytosine showed similar peak and trough levels. Adverse effects of flucytosine therapy included one case each of reversible nausea, diarrhea, elevated transaminase levels, and thrombocytopenia. No cases of bone marrow aplasia, enterocolitis, hepatitis, or death due to flucytosine toxicity were encountered. We conclude that flucytosine in combination with amphotericin B is well tolerated in myelosuppressed patients when serum flucytosine levels are serially monitored. PMID- 1457632 TI - Human babesiosis in New York State: an epidemiological description of 136 cases. AB - Epidemiological data on 136 cases of human babesiosis reported from laboratories and clinicians in the state of New York from 1982 to 1991 were reviewed. All but two patients, who had traveled to Nantucket Island in Massachusetts, acquired disease in Suffolk County, Long Island. The highest average age-group-specific annual incidence rates occurred among men > or = 80 years of age (7.72 per 100,000) and among women 70-79 years of age (3.61 per 100,000). Seven patients (5%) had previously undergone splenectomy, and 31 (23%) had evidence of concurrent Lyme disease. One hundred three patients (76%) were hospitalized, and seven (5%) died. Although the geographic distribution of this disease has remained constant, the recent introduction of babesiosis in mainland Connecticut and the spread of Lyme disease in New York suggest that the geographic distribution of babesiosis could also spread in New York. PMID- 1457633 TI - Culture isolation of Acanthamoeba species and leptomyxid amebas from patients with amebic meningoencephalitis, including two patients with AIDS. AB - Acanthamoeba species and leptomyxid organisms are free-living amebas that cause meningoencephalitis, primarily in immunocompromised patients. We report the isolation and culture of Acanthamoeba species and leptomyxid amebas from four patients with fatal amebic meningoencephalitis. Acanthamoeba species were cultured from brain abscess specimens from three immunocompromised patients (including two patients with AIDS). In the case of the fourth patient, who had no identifiable immunodeficiency, leptomyxid amebas were cultured from a specimen from a subcutaneous nodule and were identified in amebic granulomas in brain tissue by the indirect immunofluorescence test. Persons with advanced infection due to the human immunodeficiency virus may be at increased risk for amebic meningoencephalitis, but the diagnosis should be considered in the differential diagnosis of any immunocompromised patient with cerebral abscesses. PMID- 1457634 TI - The management of pregnancies complicated by genital infections with herpes simplex virus. AB - In this review we summarize current knowledge related to the identification of pregnancies that may be complicated by genital herpes and describe the consequences of maternal infections with genital herpes. We address the implications of this information for the management of genital herpes during pregnancy and at delivery and for the care of neonates exposed to herpes simplex virus at delivery. On the basis of the current data, we cannot make specific recommendations concerning many of the clinical problems that are caused by herpes simplex virus infections in pregnant women. We identify and discuss unresolved questions about optimal management. PMID- 1457635 TI - Successful treatment of disseminated nocardiosis complicated by cerebral abscess with ceftriaxone and amikacin: case report. AB - We report the case of an 85-year-old female patient who suffered from disseminated Nocardia asteroides infection complicated by a cerebral abscess. Treatment with amikacin for 2 weeks and ceftriaxone for 6 weeks led to complete recovery, and there was no recurrence of disease over a follow-up period of 12 months after therapy. The use of ceftriaxone in combination with amikacin might significantly shorten the duration of treatment for patients with disseminated nocardiosis. This combination of antibiotics merits further investigation with use of a larger sample of patients. PMID- 1457636 TI - Guidelines for the evaluation of new anti-infective drugs for the treatment of urinary tract infection: additional considerations. PMID- 1457637 TI - Stomatococcus mucilaginosus meningitis in a child with leukemia. PMID- 1457638 TI - Imipenem in the treatment of lung infections due to Mycobacterium fortuitum and Mycobacterium chelonae: further experience. PMID- 1457639 TI - Infection of the psoas muscle secondary to Streptococcus pneumoniae infection. PMID- 1457640 TI - No serologic evidence of borna disease virus in patients with chronic fatigue syndrome. PMID- 1457641 TI - Acute pancreatitis associated with Campylobacter jejuni bacteremia. PMID- 1457642 TI - Evans's syndrome triggered by recombinant hepatitis B vaccine. PMID- 1457643 TI - Kingella denitrificans as a cause of granulomatous disease in a patient with AIDS. PMID- 1457644 TI - Rhabdomyolysis, infection due to the human immunodeficiency virus, and staphylococcal bacteremia. PMID- 1457645 TI - Identification of Campylobacter laridis. PMID- 1457646 TI - Another case of Pneumocystis carinii pneumonia in a patient with dyskeratosis congenita (Zinsser-Cole-Engman syndrome) PMID- 1457647 TI - Effects of antimalarial chemoprophylactic agents on the viability of the Ty21a typhoid vaccine strain. PMID- 1457648 TI - Isolation of Borrelia burgdorferi from a patient infected in Maryland. PMID- 1457649 TI - Native valve endocarditis due to Corynebacterium pseudodiphtheriticum. PMID- 1457650 TI - Streptococcus pneumoniae peritonitis secondary to genital tract infection in a previously healthy woman. PMID- 1457651 TI - Cerebrospinal fluid adenosine deaminase levels in a patient with cryptococcal meningitis. PMID- 1457652 TI - Candidal mitral endocarditis and long-term treatment with fluconazole in a patient with human immunodeficiency virus infection. PMID- 1457653 TI - Drug interactions in patients with AIDS. PMID- 1457654 TI - Seven cases of bacteremia due to Ochrobactrum anthropi. PMID- 1457655 TI - Group B streptococcal infection of a pacemaker wire following sigmoidoscopy. PMID- 1457656 TI - Thrombosis of the mesenteric vein as a complication of Mediterranean spotted fever. PMID- 1457657 TI - Use of tetracycline for treatment of Vibrio vulnificus infections. PMID- 1457658 TI - Recurrent pneumococcal bacteremia. PMID- 1457659 TI - Reactivation of tuberculosis during therapy with corticosteroids. PMID- 1457660 TI - Infections due to Rochalimaea: the expanding clinical spectrum. PMID- 1457661 TI - Cryptosporidiosis in patients infected with the human immunodeficiency virus. AB - Infection caused by Cryptosporidium species has proved to be one of the most taxing and frustrating conditions faced by clinicians caring for patients with AIDS. Unfortunately, this unique organism, which was identified as a human pathogen only shortly before the AIDS epidemic began to manifest itself, has received only minimal attention during the past decade. Dr. Carolyn Petersen, an assistant professor of medicine at the University of California, San Francisco, and a member of the Division of Infectious Diseases at San Francisco General Hospital, is a molecular parasitologist whose investigative career is focused on elucidating the biology of Cryptosporidium species. In this AIDS Commentary Dr. Petersen provides an update on recent developments in this field. PMID- 1457662 TI - Disseminated candidiasis in addicts who use brown heroin: report of 83 cases and review. AB - From November 1983 to April 1990, disseminated candidiasis was diagnosed in 83 heroin addicts at our institution. All patients had consumed brown heroin diluted in fresh lemon juice. Sixty-two (75%) had skin lesions, 41 (49%) had ocular lesions, and 35 (42%) had one or several costochondral tumors. Candida albicans was grown in culture or histopathologically identified in 34 cases (41%). The patients who had only cutaneous lesions were treated with ketoconazole, and they were all cured. The patients with ocular involvement received systemic amphotericin B with or without oral flucytosine; 29 of these patients developed varying degrees of vision loss. The method of treatment of costochondral tumors was not uniform; in 14 cases the lesions were resected. The one patient who died developed endocarditis involving the aortic valve. Cases of pleuropulmonary involvement, spondylitis, and large-joint arthritis have also been described among the 300 cases reported in the reviewed literature. This is a new syndrome of candidal infection in drug addicts who use brown heroin; ocular lesions are the most harmful manifestation, and loss of vision is the major sequela. PMID- 1457663 TI - Cutaneous leishmaniasis: review of 59 cases seen at the National Institutes of Health. AB - Fifty-nine cases of cutaneous leishmaniasis seen at the National Institutes of Health in Bethesda, Maryland, are reviewed. The group of patients involved was unique in that the majority were American civilians, their disease was acquired in many different endemic areas of the world, and their illnesses represented all points on the clinical spectrum of cutaneous disease. The majority of American patients acquired leishmaniasis while engaging in activities related to their occupations. Cutaneous disease acquired in the New World usually consisted of one or two lesions, while multiple lesions often characterized Old World infections with Leishmania major. Patients with chronic relapsing or diffuse cutaneous leishmaniasis were native to endemic areas and were infected at an early age. Even the localized form of cutaneous leishmaniasis was often extensive and difficult to treat. Diagnosis with culture and identification of the parasite to the subspecies level is instrumental in the selection of optimal therapy. Cutaneous leishmaniasis may be encountered increasingly often in the United States because of the frequent international travel of U.S. residents and the influx of immigrants from endemic areas of the world. PMID- 1457664 TI - Agrobacterium tumefaciens peritonitis mimicking tuberculosis. AB - Agrobacterium species have been previously implicated in the development of clinical disease. We report what we believe to be the first case of ascites caused by Agrobacterium tumefaciens in a cirrhotic patient. Since the correct diagnosis was made only after laparoscopy-guided collection of specimens from two different tissues, we suggest that Agrobacterium may be an underdiagnosed pathogen in clinical situations in which tuberculosis is considered to be the cause of high-protein ascites. PMID- 1457665 TI - Epidemiology of infections with Pseudomonas aeruginosa in burn patients: the role of hydrotherapy. AB - Pseudomonas aeruginosa remains a cause of serious wound infection and mortality in burn patients. By means of restriction fragment length polymorphism analysis and a DNA probe for the pilin gene of Pseudomonas, a lethal strain of nosocomial P. aeruginosa was identified as the cause of an outbreak of wound infections among burn patients. Environmental surveys suggested an association of the outbreak with hydrotherapy provided to many patients in a common facility. In a trial of burn wound care without hydrotherapy, overall mortality was reduced significantly, mortality associated with pseudomonas sepsis was eliminated, and the strain of P. aeruginosa associated with earlier mortality was eradicated. Moreover, fewer nosocomial pseudomonas infections, lower levels of pseudomonas resistance to aminoglycoside antibiotics, significantly fewer pseudomonas infections of skin graft donor sites, and later appearance of Pseodomonas species in burn patients were found during the period when hydrotherapy was not used. PMID- 1457666 TI - Clostridium sordellii bacteremia: case report and review. AB - Clostridium sordellii is a gram-positive, anaerobic bacillus that has rarely been implicated as a human pathogen. It produces several exotoxins, which contribute to the progressive edema and refractory shock frequently seen with human infection. There have been eight prior reports of bacteremic C. sordellii infection and seven prior reports of nonbacteremic infections not due to myonecrosis of skeletal muscle. Mortality was 50% in the bacteremic group and 71% in the nonbacteremic group. Mortality correlated with both shock and leukemoid reaction at presentation. We present a case of C. sordellii sepsis in an asplenic patient with sickle beta thalassemia and inflammatory bowel disease, and we review the literature. PMID- 1457667 TI - Aerobic and anaerobic microbiology of external otitis. AB - Microbiological and clinical data from 46 patients with external otitis were retrospectively evaluated. Specimens were processed for isolation of aerobic and anaerobic bacteria. A total of 42 aerobic bacteria, 22 anaerobic bacteria, and 3 Candida albicans organisms were recovered. Aerobic bacteria only were isolated from 31 patients (67%), anaerobic bacteria only were isolated from 8 (17%), and mixed aerobic and anaerobic bacteria were isolated from 4 (9%). C. albicans alone was recovered from two patients (4%), and the organism was mixed with aerobic bacteria in one case (2%). The most common isolates were Pseudomonas aeruginosa (19 instances), Peptostreptococcus species (11), Staphylococcus aureus (7), and Bacteroides species (5). One isolate was recovered from 30 patients (65%), 2 isolates were recovered from 11 (24%), and 3 isolates were recovered from 5 (11%). beta-Lactamase activity was detected in 32 isolates recovered from 27 specimens (59%). These data illustrate the polymicrobial nature of external otitis in one-third of the patients and the role of anaerobic bacteria in one quarter of them. Further prospective studies are warranted for evaluating the role of anaerobic bacteria in this infection and the therapeutic implications of these findings. PMID- 1457668 TI - Protothecosis complicating prolonged endotracheal intubation: case report and literature review. AB - Prototheca species are ubiquitous, aerobic, unicellular algae closely related to the green algae Chlorella. Their involvement in human disease--in both immunocompetent and immunocompromised patients--has been reported with increasing frequency. The wide array of presentations has included cutaneous, subcutaneous, mucosal, bursal, catheter-related, and (in rare instances) systemic disease. We report a case of protothecosis complicating prolonged endotracheal intubation presenting as a nasopharyngeal ulceration with a soft-tissue mass, and we review the presentation, treatment, and outcome of the 59 previously reported cases of protothecosis. Optimal therapy for protothecosis includes excision (where possible) followed by systemic administration of amphotericin B; the sole exception is in the case of olecranon bursitis, where excision alone appears curative. The role of the newer imidazoles is yet to be determined. PMID- 1457669 TI - Fever of unknown origin: review of 86 patients treated in community hospitals. AB - This study describes the clinical features of fever of unknown origin (FUO) in 86 patients in a community setting from 1984 to 1990. Infectious diseases remain the most common category of illnesses causing FUO; in this study, infectious diseases including recently described diseases--such as AIDS (three cases) and Lyme disease (one case)--caused FUO in 28 patients. Although percutaneous computed tomography-guided procedures were useful for obtaining diagnostic specimens (15 cases), a noninvasive approach established the diagnosis in many instances (37 cases). In all but nine cases, diagnostic testing was guided by abnormalities detected during the physical examination or routine laboratory tests. PMID- 1457670 TI - Systemic manifestations of invasive amebiasis. AB - Eighty-four patients with serious infection due to Entamoeba histolytica were evaluated for systemic complications by objective criteria for dysfunction of the organ systems normally assessed in surgical sepsis. Of 71 patients with amebic liver abscess (ALA), 41% had systemic complications and 13% had more than one organ system involved. Patients > or = 40 years of age and those being treated with steroids were at significantly increased risk of developing complications (P < or = .05). The erythrocyte sedimentation rate and the levels of the acute-phase markers C-reactive protein (CRP) and serum amyloid A (SAA) were significantly elevated in patients with ALA over values in those without ALA (P < or = .05). ALA patients with complications had lower CRP and SAA concentrations than those without complications (P < or = .05). Blood and liver aspirates in ALA patients were usually bacteriologically sterile. The pathogenesis of systemic complications and the associated acute-phase response requires further study, and ways of predicting disease severity and intervening therapeutically must be devised. PMID- 1457671 TI - Persistent fever in association with infective endocarditis. AB - Fever persisting despite adequate antimicrobial therapy for endocarditis can be an ominous sign. To evaluate the significance of persistent fever in this situation, we reviewed the records of patients at three hospital affiliates of Albert Einstein College of Medicine. Twenty-six patients with 27 episodes of endocarditis and fever lasting for > or = 2 weeks despite appropriate antimicrobial therapy were identified and compared with a matched cohort of 26 patients with endocarditis but without prolonged fever. The median duration of fever in the former group was 35 days. Cardiac infection caused fever in 13 of these patients, seven of whom had myocardial abscesses. Additional causes of infection included drug treatment, nosocomial transmission of pathogens, and pulmonary emboli. Sixteen patients required cardiac surgery (seven on an emergent basis), whereas only two controls underwent such a procedure (P < .001). Twenty two patients with persistent fever and five controls developed nosocomial complications (P < .001). Six patients with fever died, five from endocarditis related complications. Thus persistent fever often indicates complicated endocarditis. We present an approach for the evaluation of the patients affected by this condition. PMID- 1457672 TI - Septicemia in 980 patients at a university hospital in Berlin: prospective studies during 4 selected years between 1979 and 1989. AB - A total of 980 episodes of clinically and bacteriologically proven septicemia were included in four prospective 1-year studies at a 1,300-bed university hospital in Berlin between 1979 and 1989. The incidence was 8.1 per 1,000 admissions. The percentage of patients with severe underlying diseases increased significantly from 67% to 95% over the decade. Septicemia due to gram-positive bacteria decreased from 47.3% in 1979 to 43.7% in 1986 and increased again to 51.2% in 1989. Septicemia due to gram-negative organisms decreased constantly from 45.0% in 1979 to 39.8% in 1989. The most frequently isolated species were Escherichia coli (26.4%), Staphylococcus aureus (18.9%), coagulase-negative staphylococci (10.2%), enterococci (7.7%), viridans streptococci (6.4%), Klebsiella species (5.5%), and pneumococci (5.0%). The overall mortality rate decreased significantly from 33.6% in 1979 to 20.8% in 1989. Mortality for episodes of septicemia due to gram-positive bacteria (25.5%) was higher than that for septicemia due to gram-negative bacteria (18.3%). Mortality rates associated with polymicrobic and fungal septicemia were higher than the overall mortality rate. PMID- 1457673 TI - Biocompatibility of particulate polymethylmethacrylate bone cements: a comparative study in vitro and in vivo. AB - The biocompatibility of particles of four different commercial polymethylmethacrylate (PMMA) bone cements was evaluated by exposing human synovial fibroblasts and mouse peritoneal macrophages to particles of cement. Cell integrity and inflammatory potential were assessed using enzyme release and microscopical examination. Results suggested the occurrence of cell damage in both cell types and macrophage studies indicated inflammatory potential. The response in vivo was investigated by intra-articular injection of the particles into mouse knee joints. Clinical and histological evaluation was performed over 2 52 wk. Particles of all four cements were well tolerated in the joints. PMID- 1457674 TI - Cellular reaction on the intraperitoneal injection of four types of polylactide particulates. AB - Four types of polylactide particulates, P-L-LA 100, 250, 550 KD and a P-DL-LA 400 KD were injected into the peritoneal cavity of mice. The inflammatory reaction showed an increase in cell number (mainly neutrophilic granulocytes) up to 48 h after which the cell numbers decreased below the control (phosphate-buffered saline). All four polylactide particulates aggregated and intermingled with inflammatory cells. The aggregates remained throughout the investigation period of 6 months. Quantitative measurements showed that standardization of the particle form and size is essential. From this study and other experiments in which calcium phosphates and asbestos were injected intraperitoneally, it is concluded that the inflammatory response observed in the peritoneal cavity is related to the type of material injected and probably to form and size of the individual particles, but not to molecular weight. PMID- 1457675 TI - Permucosal implantation pilot study with HA-coated dental implant in dogs. AB - The histological response of transmucosal one-stage titanium dental implants coated with hydroxyapatite is described. The gingival adhesion to the implant was examined with regard to coated, partially coated or non-coated surfaces in the cervical region. From each coating type, 9 implants were inserted into dogs. Six months after the insertion, 19 implants could be evaluated, but 8 implants were lost. From these 19 implants, 6 implants showed severe pockets with inflammation up to the bony tissue. The 13 successful implants showed direct bone bonding with the hydroxyapatite coating and adhesion of submucosal connective tissue to the implant surface, with inflammation. The marginal gingiva showed slight inflammation. A totally coated implant will probably introduce inflammation by debris formation against the rough implant surface more easily. The hydroxyapatite coating often disappeared in the soft tissue or in the oral cavity. Bone which directly adapted to the coating seemed to prevent it from resorption. PMID- 1457676 TI - Modification of the biocompatible and haemocompatible properties of polymer substrates by plasma-deposited fluorocarbon coatings. AB - The polymerization of gases present in a low temperature plasma is a technique particularly well suited for biomedical material processing. Therefore, the possibilities this technique offers to increase the biocompatibility and haemocompatibility of polysulphone and poly(hydroxybutyrate) membranes to be used in a new bioartificial pancreas device were studied. The deposition of thin fluorocarbon coatings from an argon plasma containing perfluorohexane gave very smooth and hydrophobic surfaces without affecting the filtering properties of the treated membranes. Adding hydrogen increased the reaction yield, but gave rougher and less hydrophobic coatings. We characterized the biological properties of the treated surfaces and discussed the influence of the modified surface properties on the biological behaviour of the treated polymers. The good biocompatibility of the deposited coatings was established by following in vitro the insulin secretion of Langerhans islets cultured on the treated membranes and by examining the fibrous capsule that developed on plasma-treated polymer disks after three months of in vivo incubation in the peritoneum of Wistar rats. Rough and haemocompatible films of poly(hydroxybutyrate) and smoother, but more thrombogenic, polysulphone films were treated by perfluorohexane and perfluorohexane + H2 plasmas to study the relative influence of surface roughness and surface energy on polymer thrombogenicity. In vitro protein adsorption and total blood clotting tests proved that the surface roughness influences the thrombogenicity more than the other surface properties. This study seems to show that the plasma deposition of smooth and hydrophobic fluorocarbon coatings can increase the biocompatibility and reduce the surface thrombogenicity of the treated membranes without affecting their filtering properties. PMID- 1457677 TI - Human serum albumin as a probe for surface conditioning (opsonization) of block copolymer-coated microspheres. AB - The adsorption of human serum albumin to polystyrene microspheres sterically stabilized with block copolymers, was investigated using photon correlation spectroscopy and laser doppler anenometry. The block copolymers used were non ionic surfactants of the poloxamer and poloxamine series made of polyoxyethylene and polyoxypropylene chains. Photon correlation spectroscopy and laser doppler anenometry showed that the coating reduced the adsorption of the protein to the polystyrene microspheres surface. Quantitative studies using 125I-labelled human serum albumin and sodium dodecyl sulphate-polyacrylamide gels (in combination with densitometry), were employed to evaluate the adsorption of human serum albumin to uncoated and coated polystyrene microspheres. They confirmed that the hydrophilic polyoxyethylene steric layer, created by coating with the block copolymers, reduced the adsorption of human serum albumin. Moreover, the amount of human serum albumin adsorbed was related to the polyoxyethylene content of the block copolymers. PMID- 1457678 TI - Controlled drug release from implantable matrices based on hydrophobic polymers. AB - Reports on the controlled release of drugs, including macromolecular drugs, from silicone elastomers and ethylene-vinyl acetate copolymers, based on the formation of channels and cracks in the polymer, are reviewed. Aqueous interconnected pores are produced by osmotically active additives or by using loads of water-soluble drugs exceeding the percolation threshold. The release is generally proportional to the square root of time (t1/2). Nevertheless, pseudo-zero-order release kinetics can be obtained by adequately controlling the formulation variables. The factors controlling the release pattern and rate are discussed. In vivo applications of these types of systems are also considered. PMID- 1457679 TI - Antibacterial activity and mutagenicity studies of water-soluble phosphazene high polymers. AB - Eight water-soluble phosphazene high polymers, [NPR2]n (R, organic, water solubilizing side-group; n, approx: 15,000) and the small-molecule counterparts of the polymers were examined for antibacterial activity against six different strains of bacteria (Escherichia coli, Salmonella typhimurium (TA 100), Salmonella pullorum, Streptococcus faecalis, Bacillus subtilis and Pseudomonas aeruginosa). Antibacterial testing was carried out by measuring zones of inhibition and changes in solution turbidity over time. In addition, the antibacterial activity of the surfaces of cross-linked poly[di(methoxyethoxyethoxy)phosphazene] (MEEP) hydrogels were investigated. A number of the high polymers, as well as the MEEP hydrogels, impeded bacterial growth. Only E. coli was unaffected by the phosphazenes. A possible explanation for the antibacterial character of the polymers is presented. The same compounds were monitored for potential mutagenic activity using the Salmonella typhimurium tester strains TA 100 and TA 98. None of the high polymers or their small molecule analogues showed mutagenic activity in either strain of Salmonella at the concentrations tested. The use of these materials as coatings for artificial implants is discussed. PMID- 1457680 TI - Poly(ethylene oxide)-graft-poly(L-lysine) copolymers to enhance the biocompatibility of poly(L-lysine)-alginate microcapsule membranes. AB - A graft copolymer having poly(L-lysine) (PLL) as the backbone and monomethoxy poly(ethylene glycol) (MPEG) as pendent chains was synthesized. This polycationic copolymer was used to form microcapsules with sodium alginate, a polyanion. Microcapsules and model surfaces formed with PLL-graft-MPEG demonstrated reduced protein adsorption, complement binding and cell adhesion in vitro compared to materials with unmodified PLL. Microcapsules with PLL-g-MPEG on the surface were seen to be much more biocompatible than the widely used alginate/PLL/alginate microcapsule in a mouse intraperitoneal implant model. The graft copolymers demonstrated a lower affinity for alginate and increased microcapsule permeability more than PLL. To correct this, pentalayered alginate/PLL/alginate/PLL-g-MPEG/alginate microcapsules were fabricated, and these demonstrated both appropriate permselectivity and enhanced biocompatibility. PMID- 1457681 TI - Epifluorescent video microscopy (EVM) for platelet-biomaterial interactions: elimination of photoactivation and dye effects. AB - The use of two intracellular dyes for epifluorescent video microscopy (EVM) in observations of cell-surface interactions is evaluated and discussed. This methodology permits determinations of cell adhesion, detachment and movement at the surfaces of biomaterials in the presence of flow and physiological haematocrit. Two tests, one which examines for the effect of incident light on platelet adhesion and one which checks for sufficient light for accurate observation of cells, have been designed. Evaluations were made of the adhesion of platelets labelled with the fluorescent dyes mepacrine and acridine orange, used singly and in combination. The use of a number of light level-dye level combinations with glass and several polymers and the addition of a plasma level of fibrinogen did not show any photoactivation effects. This methodology paves the way for longer than previous exposures to light with our system, from 1 min up to 30 min now. Washed platelet suspensions are preferred; these allow for the selective labelling of specific cells and the removal of dye from the surface of the cell. PMID- 1457682 TI - Effect of electrostatic forces on the dynamic rheological properties of injectable collagen biomaterials. AB - Injectable collagen is a concentrated dispersion of phase-separated collagen fibres in aqueous solution used to correct dermal contour defects through intradermal injection. The effect of electrostatic forces on the rheology of injectable collagen was studied by observation of the birefringence of collagen fibres through a polarizing microscope as well as by oscillatory rheological measurements on dispersions of varying ionic strengths (0.06-0.30). The birefringence of fibres progressively increased as ionic strength was reduced from 0.30 to 0.06. The linear viscoelastic measurements displayed a logarithmic relationship between storage (and loss) moduli and frequency over oscillation frequencies of 0.1-100 rad/s. The associated relaxation time spectra, interpreted using the theory of Kamphuis et al. for concentrated dispersions, show that collagen fibres become more flexible as ionic strength increases. This result was analysed at the molecular level from the perspective that collagen fibres are a liquid-crystalline phase of rigid rod collagen molecules which have phase separated from solution. Electrostatic forces affect the volume fraction of water present in the collagen fibres which in turn alters the rigidity of the fibres. Flexible collagen fibre dispersions displayed emulsion-like flow properties whereas more rigid collagen fibre dispersions displayed suspension-like flow properties. Changes in fibre rigidity significantly alter the injectability of collagen dispersions which is critical in clinical performance. PMID- 1457683 TI - Central connections of trigeminal primary afferent neurons: topographical and functional considerations. AB - This article reviews literature relating to the central projection of primary afferent neurons of the trigeminal nerve. After a brief description of the major nuclei associated with the trigeminal nerve, the presentation reviews several early issues related to theories of trigeminal organization including modality and somatotopic representation. Recent studies directed toward further definition of central projection patterns of single nerve branches or nerves supplying specific oral and facial tissues are considered together with data from intraaxonal and intracellular studies that define the projection patterns of single fibers. A presentation of recent immunocytochemical data related to primary afferent fibers is described. Finally, several insights that recent studies shed on early theories of trigeminal input are assessed. PMID- 1457684 TI - Recent advances in primary palate and midface morphogenesis research. AB - During the sixth week of human development, the primary palate develops as facial prominences enlarge around the nasal pits to form the premaxillary region. Growth of craniofacial components changes facial morphology and affects the extent of contact between the facial prominences. Our recent studies have focused on developing methods to analyze growth of the primary palate and the craniofacial complex to define morphological phases of normal development and to determine alterations leading to cleft lip malformation. Analysis of human embryos in the Carnegie Embryology Collection and mouse embryos of cleft lip and noncleft strains showed that human and mouse embryos have similar phases of primary palate development: first, an epithelial seam, the nasal fin, forms; then a mesenchymal bridge develops through the nasal fin and enlarges rapidly. A robust mesenchymal bridge must form between the facial prominences before advancing midfacial growth patterns tend to separate the facial components as the medial nasal region narrows and elongates, the nasal pits narrow, and the primary choanae (posterior nares) open posterior to the primary palate. In mouse strains with cleft lip gene, maxillary growth, nasal fin formation, and mesenchymal replacement of the nasal fin were all delayed compared with noncleft strains of mice. Successful primary palate formation involves a sequence of local cellular events that are closely timed with spatial changes associated with craniofacial growth that must occur within a critical developmental period. PMID- 1457685 TI - Salivary gland function and aging: a model for studying the interaction of aging and systemic disease. AB - This review describes an approach to examining the interaction of aging and systemic disease on a key aspect of oral physiology, salivation. The approach requires several steps: defining general health, and a specific physiological function, at different ages; defining a disease of interest and the influence of the disease on the specific physiological function; and determining if the disease can affect performance of the physiological function with increased age. PMID- 1457686 TI - Mesoderm and jaw development in vertebrates: the role of growth factors. AB - The head and neck arise during development as the result of a complex series of cellular and molecular interactions that begin in the fertilized egg. In this article, the role of an important class of molecules, growth factors, is examined in two main steps of the developmental sequence: the initial induction of mesoderm and the later induction of jaw cartilage and bone. The article focuses particularly on the roles of members of the transforming growth factor-beta (TGF beta), fibroblast growth factor (FGF), and epithelial growth factor (EGF) families in these processes and current models of growth factor involvement. Possible experiments for the future are discussed. PMID- 1457687 TI - Artificial cells in immobilization biotechnology. AB - Artificial cells contain biologically active materials. Artificial cells containing adsorbents have been a routine form of treatment in hemoperfusion for patients. This includes acute poisoning, high blood aluminum and iron, and supplement to dialysis in kidney failure. Artificial cells are being tested for use as red blood cell substitutes. Artificial cells encapsulated cell culture are being tested in animals for the treatment of diabetes and liver failure. A novel 2 step method has prevented xenograft rejection. Artificial cells containing enzymes are being studied for treatment in hereditary enzyme deficiency diseases and other diseases. Recent demonstration of extensive enterorecirculation of amino acids in the intestine has allowed its oral administration to deplete specific amino acids. Artificial cells containing complex enzyme system convert wastes like urea and ammonia into essential amino acids. Artificial cell is being used for the production of monoclonal antibodies, interferons and other biotechnological products. It is also being investigated for drug delivery, and for use in other applications in biotechnology, chemical engineering and medicine. PMID- 1457688 TI - Semi-selective immunoadsorption treatment in myasthenia gravis. AB - We treated some patients with severe generalized myasthenia gravis (MG) with semi selective adsorption by plasma perfusion(PP) on IM-T350 column. We studied efficiency and undesired effects of the employed material to verify the safety and effectiveness of methodology. Thus a treatment protocol has been prepared: 6 PP per treatment cycle; 3-7 days between PP sessions; plasma to treat per session 1,2 lt; only one adsorbent column for every cycle. Our experience, on 13 cycles of treatment, showed that PP in autoimmune MG has provided good clinical results without any improvement in genetic MG. PMID- 1457690 TI - Adsorption treatment in hyperlipidemia. AB - Clinical LDL- adsorption has made overwhelming progress in recent years. Thus, immunoadsorption with polyclonal anti-LDL-antibodies and chemoadsorption using the dextransulfate system have been applied successfully for selective LDL removal in routine clinical plasma treatment of hypercholesterolemic patients suffering from coronary artery disease. Clinical pilot studies showed good results using immunoadsorption with anti-LDL-F(ab)-columns. Promising laboratory results have been achieved using immunoadsorption with monoclonal LDL-antibodies, polyacrylate/fractogel and macroporous cellulose. While these systems need a primary separation step for cells and plasma, the integrated plasma separation/adsorption device and the LDL-hemoperfusion module using E 280590 can even treat whole blood. Thus, these systems hold a great promise for the future. PMID- 1457689 TI - Phosphate removal by resin hemoperfusion efficacy and biocompatibility of a new exchange resin. AB - A new coated anionic exchange resin for blood purification specifically designed to remove phosphates was experimentally employed in animals. 3 pigs, in which uremia had been surgically induced, underwent 6 extracorporeal hemoperfusion sessions (2 per pig) with a cartridge containing 100 gr of resin. The phosphate clearance proved satisfactory, values being 120 ml/min after 10' and around 80 ml/min after 2 hours. The biocompatibility of the resin and of the coating membrane was satisfactory. The negligible variation in pH and plasma bicarbonate during all sessions confirmed the low absorption by the tested resin of other blood anions competing with phosphate. PMID- 1457691 TI - Extracorporeal elimination of carbamazepine by haemoperfusion. AB - The clearance of the haemoperfusion cartridge H 200 C Tekin was determined in vitro for blood dissolved carbamazepine to test the efficiency of haemoperfusion treatment. In the first hour of in vitro haemoperfusion test of pig blood (concentration of carbamazepine 1084 mg/l) a clearance of 190 ml/min was obtained, which declined slightly to 150 ml/min after 4 hours. In a second test the elimination of carbamazepine from albumin solution was proven to be more than 1000 mg of carbamazepine after a four hour perfusion period using teflon coated charcoal. These results are in accordance with the clinical course of a 30 years old male patient who presented with severe hypoxaemia due to acute intoxication by 6 g carbamazepine. The carbamazepine blood level was 33.7 mg/l. Charcoal haemoperfusion was started immediately. A dramatic improvement of clinical symptoms was already observed during haemoperfusion. The carbamazepine serum level was 18.6 mg/l after 4 hours of haemoperfusion. PMID- 1457692 TI - Hybrid artificial pancreas: islet transplantation inside membrane bioreactors. AB - The use of pancreatic islet transplantation in membrane bioreactors put in vascular circuits aims at resetting the glucose homeostasis in diabetic or pancreatectomized patients, avoiding immune host rejection. Our experience was carried out at following stages: porcine pancreas explantation and enzymatic separation of endocrine tissue from exocrine fraction by collagenase; evaluation of islet functionality (culture tests); in vitro tests of the islets-bioreactor system, to assess the metabolic response to the glucose; in vivo evaluation to assay the haemodynamic behaviour. The trials showed a good metabolic bioreactor functionality and a decreasing incidence of coagulative problems. PMID- 1457693 TI - Treatment of uraemic hyperphosphatemia with calcium acetate: a safe alternative to calcium carbonate. AB - Clinical usefulness of calcium acetate (CAA) as phosphorus binder was assessed in 19 stable hemodialysis patients with persistent hyperphosphatemia. All were dialysed thrice weekly with a constant dialytic schedule and a dialysate calcium of 3.5 mEq/l. One month prior the study beginning all patients stopped assumption of Ca and vitamin D supplements. In the first period of the study CAA (mean daily doses 2.2 g) was administered for one month followed by 15 days of withdrawal. The mean serum phosphorus decreased from 7.6 +/- 1.4 to 5.8 +/- 0.8 mg% (p < 0.005). After 15 days of withdrawal mean serum phosphorus reached the pretreatment value. Then the patients entered a long term study with personalized doses of CAA (between 1 and 4 g/day) and administration in 8 of them of alpha calcidol. After a mean follow-up period of 5.4 +/- 1.5 months serum phosphorus was reduced from 7.5 +/- 1.1 to 5.6 +/- 1.1 mg% (p < 0.0005) while calcemia increased from 9.0 +/- 0.7 to 9.6 +/- 0.6 mg% (p < 0.005). Only one patient developed mild hypercalcemia. We concluded that CAA is a safe alternative to calcium carbonate for the control of hyperphosphatemia of uraemic patients for the most efficient phosphorus binding and the lesser absorption of calcium. PMID- 1457694 TI - DNA-coated carbon adsorbents experimental assessment and results of severe psoriasis treatment. AB - Newly developed combined adsorbents, containing from 1 to 8 mg of thymic DNA per 1 g of the granulated or the fibrous carbonic matrix, demonstrated good biocompatibility and selectivity for DNA- and DNP-binding substances. In a group of 14 patients with severe psoriasis (uncontrol trial) a single hemoperfusion procedure through DNA-coated granulated synthetic carbons (perfusion volume was 2.5-3.1 L, sorbent quantity was 30 g) resulted in complete remission in 6 patients and in substantial improvement of clinical status in 6 other patients. A positive effect was observed in 4 patients during 7-11 months; in 8 patients it is being observed for more than 29-33 months. The double-blind tests in the group of patients subjected to hemoperfusion through the DNA-coated charcoal (27 people) and uncoated charcoal (9 people) showed the full-scale remission in 55.5% and 11.2% respectively. The authors believe that the DNA-coated activated carbons can be an effective therapeutic procedure for treatment of numerous immuno dependent diseases and states associated with disorders in the kinetics of cell division. PMID- 1457695 TI - Removal of beta 2-microglobulin by hemodialysis and hemofiltration: a four year follow up. AB - Efficient removal of total body burden beta 2-Microglobulin (beta 2-M) in uremia is a continuing challenge, as dialysis-related amyloidosis represents a major complication of chronic renal replacement therapy. To investigate long-term beta 2-M removal we studied 3 groups of stable end-staged renal failure patients over a period of 4 years; we compared low flux (cuprophane) hemodialysis (n = 12), high flux (polysulfone) hemodialysis (n = 12) and hemofiltration using high flux polysulfone (n = 8). In contrast to the cuprophane membrane, the polysulfone membrane eliminated considerable amounts of beta 2-M. This was associated with a sustained reduction of predialysis serum beta 2-M-levels (by 20%). Compared with high flux hemodialysis, hemofiltration provided a 50% higher elimination of beta 2-M. Thus, our long-term evaluation of beta 2-M removal suggests that hemofiltration rather than hemodialysis may be the treatment of choice for delaying the incidence of dialysis-related amyloidosis. PMID- 1457696 TI - The whole molecule design approach to drug discovery. AB - An approach to drug design and lead generation is presented which attempts to retain the qualities of traditional drug design and leave control with the bench scientist, whilst harnessing the power of computers to handle the combinatorial explosion of ideas. A computer language, ALEMBIC, is used to collate the ideas of the scientists. The resulting list of potential molecules is then parameterised using whole molecule descriptors. Based on these descriptors, appropriate statistical techniques are used to generate sets of molecules retaining the maximum amount of the information inherent in all possible combinations of the scientists ideas. PMID- 1457697 TI - Synthesis and ACE inhibitory activity of the stereoisomers of perindopril (S 9490) and perindoprilate (S 9780). AB - Perindopril, a powerful ACE inhibitor contains 5 chiral carbons, thus there is the possibility of 2(5) = 32 stereoisomers for the general structure 1. These 32 stereoisomers were synthesized by cross-coupling the 8 stereoisomers of perhydroindole 2-carboxylic acid benzylester with the 4 stereoisomers of 2-(1 carbethoxybutylamino) propionic acid 4, then hydrogenating the resulting benzylesters. Each stereoisomer of perindopril furnished by saponification the corresponding diacid stereoisomer 2 of perindoprilate which is the active form of perindopril. For each of the 32 stereoisomers 2 the in vitro ACE inhibitory potency (IC50) was determined. Four of them, including perindoprilate, had activities in the nanomolar range, and four more were ca. 10 x less active. The four acid esters 1 corresponding respectively to the four most active diacids 2 in vitro were studied (1 mg/kg via the oral route) for their in vivo activity in dogs. It could be concluded that p.o. absorption of the active acid esters 1 and their activation to the active diacid 2 depended only on the chiralities of the two ring junction carbons of the perhydroindole ring. PMID- 1457699 TI - Synthesis and antitumor activity of poly(ethylene glycol)s linked to 5 fluorouracil via a urethane or urea bond. AB - In order to provide a macromolecular prodrug of 5-fluorouracil (5FU) with reduced side-effects and exhibiting strong antitumor activity, 5FU was covalently linked to poly(ethylene glycol) (PEG) via a urethane or urea bond. For the purpose of evaluating the release behavior of 5FU, the hydrolysis of the urethane or urea bond in the obtained conjugate of PEG-end capped with 5FU was investigated in vitro at 37 degrees C in aqueous solution media. The survival effect for the conjugate was assessed in vivo against p388 lymphocytic leukemia in female CDF1 mice by intraperitoneal (i.p.) transplantation/i.p. injection. The effects of a hydrophobic hexamethylene spacer group, the end group and the number n of ethylene oxide (EO) units in PEG on the release behavior of 5FU and the survival effect were investigated. The release rate of 5FU from the 5FU-terminated PEG conjugates via urethane or urea bond was very fast. However, it became slow with increasing n of EO units in PEG and was depressed by the introduction of hydrophobic spacer group. The 5FU-terminated PEG conjugates obtained exhibited significant survival effects against p388 leukemia mice i.p./i.p. Especially, the methoxy PEG (n = 113)/urethane/hexamethylene/urea/5FU conjugate showed the strongest survival effect among the synthesized 5FU-capped PEG conjugates via urethane or urea bond compared to free 5FU against p388 leukemia mice. These conjugates obtained did not display an acute toxicity even in high dose ranges. PMID- 1457700 TI - [Equity, the national health system and the autonomous areas]. PMID- 1457698 TI - Molecular modeling of adenosine receptors. I. The ligand binding site on the A1 receptor. AB - The amino acid sequence of the canine adenosine A1 receptor and the atomic coordinates of a structurally related protein, bacteriorhodopsin, were combined to generate a three-dimensional model for the adenosine A1 receptor. This model consists of seven amphipathic alpha-helices, forming a pore that has a rather distinct partition between hydrophobic and hydrophilic regions. Subsequently, a highly potent and selective ligand, N6-cyclopentyladenosine, was docked into this cavity. A binding site is proposed that takes into account the conformational characteristics of the ligand, obtained from indirect modeling studies by the 'active analog approach'. Moreover, it involves two histidine residues that were shown to be important for ligand coordination from chemical modification studies. Finally, the deduced binding site was used to model other potent ligands that could all be accommodated consistent with earlier biochemical and pharmacological findings. PMID- 1457701 TI - [Limitations of primary care teams in taking care of mental patients]. PMID- 1457702 TI - [Functional capacity of patients over 65 according to the Katz index. Reliability of the method]. AB - OBJECTIVE: To find functional capacity of elderly patients by using the Katz Index, which measures the "Basic Activities of Daily Life". To examine how reliable the Katz Index is in the Primary Care field. DESIGN: Descriptive crossover study. Assessment of the measuring instrument's internal consistency and reliability, using a test-retest method. SITE. Otero Health Area, in Oviedo. PATIENTS OR OTHERS PARTICIPANTS: This was a random sample, ordered by age and gender, of people over 65 who used the Otero Health centre. MAIN MEASUREMENTS AND RESULTS: The elderly population made up 12.86% of our base Health Area. The Katz Index showed that 81.6% of the elderly in the sample were independent in all their functions. A significant age difference was found. Internal consistency was measured by Cronbach's Alpha and was 0.8612 for nurses and 0.8362 for doctors. The correlation coefficient within Sperman's estimated observer was r = 0.936074. Kappa was 0.8436 (p < 0.0000) for the different observers, i.e. nurses or doctors. CONCLUSIONS: Most of the elderly patients in our base Health area possess full functional capacity, at the level of the routine activities of their daily life. The Katz Index is a reliable method of evaluating elderly peoples' functional capacity, at the Primary Care level. It can be used by any professional in the health team. PMID- 1457703 TI - [Calibration and safety of sphygmomanometers in health centers of Murcia]. AB - OBJECTIVE: To find the levels of calibration, safety and physical faults in the sphygmomanometers used in Health Centres. DESIGN: A multi-centre, observational, descriptive and crossover study. SITE. 7 Health Centres in the urban zone of Murcia and nearby towns. All the sphygmomanometers in the 7 Health Centres, that is 80 aneroid and 62 mercury ones. MAIN MEASUREMENTS AND RESULTS: It needs high lighting that 43.7% of the aneroid sphygmomanometers and 12.3% of the mercury ones were wrongly calibrated. We noted that 20% of the measurements made with wrongly calibrated aneroid sphygmomanometers had a margin of error above +/- 8 mmHg, with a tendency towards under-registering. We found very significant differences between the average arterial pressure measured by aneroid instruments as against mercury ones (p < 0.001). The number of sphygmomanometers which show a margin of error greater than +/- 3 mmHg at every level of pressure is significantly greater in aneroid instruments than in mercury ones (p < 0.001). We found physical faults in 23.9% of the instruments. CONCLUSIONS: We consider the number of wrongly calibrated aneroid sphygmomanometers to be excessively high. Therefore mercury ones should be used whenever possible and particularly during diagnosis and treatment. Both aneroid and mercury sphygmomanometers should be regularly checked, using a proper procedure. Mercury instruments set at zero are correctly calibrated and can be used as a model for checking aneroid ones. PMID- 1457704 TI - [Oral-dental hygiene habits in 12-year-old schoolchildren of the city of Huesca]. AB - OBJECTIVE: To study dental hygiene habits and their relationship to dental caries. DESIGN: A descriptive epidemiological crossover study, based on observation. SITE. Schools in the city of Huesca. PATIENTS: Every child in the 7th grade (i.e. 12 years old) of Basic General Education (EGB) in the city of Huesca. MAIN MEASUREMENTS AND RESULTS: We found that only 43.83% of the children (689 in all: 340 male, 349 female) brushed their teeth every day. 49.20% had had a dental check-up during the previous year. We noted a significant link between cariogenic factors, especially those to do with tooth-brushing and the consumption of sweets, and the actual existence of caries. CONCLUSIONS: There was a notable lack of dental hygiene, both around the questions of using a tooth brush and in eating habits. There was little primary (the use of fluorides or dental hygiene) or secondary prevention (programmes of odonto-stomatologic care). PMID- 1457705 TI - [Postvaccinal reactions to simultaneous administration of the triple viral, oral polio and diphtheria-tetanus vaccines compared with their administration in sequence]. AB - OBJECTIVE: To compare the frequency and characteristics of post-vaccination reactions, between on the one hand the simultaneous administration of the Oral Antipolio (OP), the Triple Virus (TV) and the Anti-Diphtheria and Anti-Tetanus (DT) vaccines; and on the other hand, their administration in sequence. DESIGN: Prospective study with interventions, with a non-random, non-blind determination. SITE. Survey covering the mothers of infants vaccinated at 24 vaccination centres in Mala province. PARTICIPANTS: 490 infants vaccinated during their second year of life. 263 had the vaccines administered simultaneously and 227 in sequence. INTERVENTIONS: Simultaneous administration of the TV, OP and DT vaccines at 15 months; as against the administration of TV at 15 months, followed by OP and DT at 18 months. MAIN RESULTS: 78 infants (29.66%) suffered a reaction that could be attributed to the vaccination after the simultaneous administration of TV, OP and DT; and 86 infants (37.88%) after one of the two occasions of vaccination in the administration in sequence: 27.31% after the TV, 17.18% after the OP-DT and 6.62% after both. CONCLUSIONS: The safety of simultaneous administration, taken together with data coming from other studies on its immunogenic effectiveness, reaffirms the usefulness of simultaneous administration of TV, OP and DT vaccines at 15 months, as a strategy to improve vaccine coverage of infants in their second year of life. PMID- 1457706 TI - [Active pulmonary tuberculosis in the community. Current presentation]. AB - OBJECTIVE: To discover how patients in a provincial general hospital, diagnosed as having pulmonary tuberculosis had first clinically and radiologically presented. DESIGN: This was a retrospective observational study. SITE. The San Jorge de Huesca General Hospital. The period of study was between January, 1986, and December, 1989. PATIENTS AND OTHERS PARTICIPANTS: Those studied were the 59 patients diagnosed as having active pulmonary tuberculosis during the study period. MAIN MEASUREMENTS AND RESULTS: The average age of the patients was 45.6 +/- 19.25 SD. There was greater occurrence in males. The most common form in which the disease first appeared was thoracic symptomatology (59%), followed by constitutional syndrome (45.7%). 8 patients were addicted to drugs taken parenterally (ADVP), of whom 4 were HIV-positive (6.8%). The most common radiological pattern was ulcero-caseous. CONCLUSIONS: We underline the importance of diagnostical awareness at the Primary Care level in order to rapidly begin the correct treatment; and thus fight the adverse epidemiological situation caused by tuberculosis today. PMID- 1457707 TI - [Smoking in primary schools]. AB - OBJECTIVE: To analyze policies related to tobacco use in primary schools. DESIGN: Cross-sectional study. SITE. Primary schools in the city of Barcelona, Spain. PARTICIPANTS: Schools principals of a representative sample of the 493 primary schools in the city; 98 of the 100 selected schools participated. MEASUREMENTS AND MAIN RESULTS: Schools are aware of the existing regulations in Catalonia. Although there is no smoking in classrooms--which represents an improvement compared with previous years--, visible use of tobacco by adults is frequent. Usually there is no formal policy on smoking. No smoking signs are rare, and usually there is no designated person with responsibilities for the enforcement of smoking policies. Schools rarely address smoking outside school hours, and adults are often allowed to smoke in the court, the dining room or the aisles. There are no significant differences between public and private schools. CONCLUSIONS: Although an improvement can be seen compared to the previous situation, smoking is still visibly present in schools. There must be specific prevention projects if schools are to have a positive influence in the social perception of smoking by schoolchildren. PMID- 1457708 TI - [Measles epidemic in Huesca. Study of cases in a health center]. PMID- 1457709 TI - [Ongoing care at the primary care level]. PMID- 1457710 TI - [Packets per year]. PMID- 1457711 TI - [Management of the aged in primary health care]. PMID- 1457712 TI - [Uses and abuses of computers in medical research]. PMID- 1457713 TI - [Factors influencing neurological care]. AB - OBJECTIVE: To analyse certain factors which contribute to the existing backlog in specialised neurological care, such as: where the patient was referred from, the reason for the appointment, tests carried out and the final diagnosis. We used a random sample of patients. DESIGN: Retrospective study of patients referred from Primary Care, who were attended as out-patients in the Neurology clinic during 1991. SITE. Health Area 2 of the Autonomous Community of Madrid. MAIN MEASUREMENTS AND RESULTS: The average number of patients per doctor sent from each one of the seven Centres studied was 7.69, with outliers of between 2 and 21, with a standard deviation of 3.95 and a rate of 51.31%. The proportion of new patients to patients having follow-up checks was 2 to 3, respectively. The differences between the number of patients sent from the different centres were found in the less serious pathologies. CONCLUSIONS: We suggest that the criteria used by Primary Care professionals and specialists should be strengthened and unified. This was one of the factors which weighed most on the quality and backlog of care. PMID- 1457714 TI - [Evaluation of the quality of care at a nursing station in a health center]. AB - OBJECTIVE: To analyse the procedures in the care of patients who attend the nursing station (NS), identify possible faults and evaluate the effect of these procedures on the patients. DESIGN: Descriptive and retrospective study concerning the quality of the NS. SITE. Primary Care. At the Molino de la Vega Health Centre, Huelva. PATIENTS OR OTHER PARTICIPANTS: The 602 people who attended the NS: patients with Hypertension, Diabetic, Obesity and osteoarticular problems. MAIN MEASUREMENTS AND RESULTS: 54.4% of the procedures show a high level of control: in the case of Hypertension, the percentage reaches 62.7% (C.I. 95%: 57.8-68%). 87.3% of diabetics treated with insulin managed to give themselves their injections. 45.4% of patients suffered more than one chronic illness. The analytical tests envisaged were carried out on 62% of those with light Hypertension and on 41.4% of those with severe Hypertension. 71.3% of patients with light Hypertension had a high rate of attendance at the station, which was correct in 93.8% of the severe cases. All categories of patients with diabetes attended with excessive frequency. CONCLUSIONS: The high level of control attained clearly shows the NS's usefulness. The high percentage of self injection achieved means that the majority of our diabetics who are treated with insulin are responsible for their own health. A fair number of patients present varied pathologies. Over-use of the NS by the large proportion of those patients with light Hypertension and diabetes implies inadequate care for other groups of patients, for example those suffering severe Hypertension. PMID- 1457715 TI - [Aneurysm of the abdominal aorta]. AB - OBJECTIVE: Three clinical cases of Aneurysm in the abdominal Aorta are presented, in order to make a clinical review of aneurysms in the abdominal Aorta (AAA) and underline the importance of their early diagnosis in Primary Care, given the risk factors. DESIGN: A retrospective, descriptive analysis of three cases of AAA from 1991. SITE. The patients studied had attended the hospital emergency department in the Alcoy Health area. MAIN MEASUREMENTS AND RESULTS: Case 1: A patient, who attended because of three days of bilateral lumbar pain of a colic type spreading to the mesogastrium, which did not respond to treatment for nephritic colic. The patient died in a few hours, with the diagnosis of hypovolaemic shock caused by a burst AAA. Case 2: A patient with generalised continuous abdominal pain, which over 12 hours had been located in the lower right hemiabdomen, who was admitted with the provisional diagnosis of acute pyelonephritis. Case 3: A patient who, after an emergency surgical intervention where the diagnosis of AAA was confirmed, presented after a month a clinical picture consistent with a cerebral vascular accident and died afterwards because of renal failure. CONCLUSION: Given the present increase of patients diagnosed in hospital as suffering AAA in our Health Area, we urge that special attention be paid to the early diagnosis of this pathology. It is important to look actively for this pathology in patients with chronic pathologies of high prevalence and include it in Primary Care preventive programmes. PMID- 1457716 TI - Cloning and expression of midecamycin 4"-acylase gene in spiramycin producing strains. AB - A recombinant plasmid p66B containing the midecamycin 4"-acylase gene was obtained by cloning this gene into plasmid vetor pIJ680 from the primary clone pCN6C5, presumably harboring the midecamycin biosynthetic gene. The expression of the midecamycin 4"-acylase gene (p66B) in spiramycin producing strains resulted mainly in the production of 4"-isovalerylspiramycin. Another positive clone pCN10F5 was discovered from the genomic library of S. mycarofacians 1748 by probing with p66B DNA BamHI-BamHI 2.3kb fragment. A BamHI-BamHI 8.0kb homologous region on pCN10F5 was determined by Southern hybridization and was subcloned into plasmids pWHM3 and pIJ680. Recombinant plasmids pWF5 and p6F5 with molecular size about 15.2kb and 13.3kb, respectively, were obtained. Transformation of spiramycin producing strains with these plasmids resulted in the production of two major components. Based on their physicochemical properties and spectral evidences, component I was identified as 4"-propionylspiramycin III, and component II as 4"-propionylspiramycin II. Southern hybridization confirmed that the BamHI-BamHI 8.0kb fragment was cloned in the spiramycin producing strain. Only pCN10F5 clone was identified from the genomic library of S. mycarofaciens 1748 when the 4"-isovaleryltransferase gene of carbomycin producing strain S. thermotolerans was used as a probe in colony hybridization. It suggests that there is a difference between the 4"-acyltransferase genes in the pCN6C5 and pCN10F5 clones. PMID- 1457717 TI - Restriction mapping and localization of GL-7-ACA acylase gene. AB - This paper presents the results about the restriction mapping of recombinant plasmids pMR5 and pMR6 containing GL-7-ACA acylase gene from Pseudomonas sp. 130, gene localization and its expression under the control of different promoters, tet, tac or lac/tac, in Escherichia coli. The analysis of gel electrophoresis of pMR5 cleaved with several kinds of restriction enzymes indicated that there is no sites of EcoRI, HindIII and ClaI but the presence of following sites: one HpaI, two XhoI, three EamHI and four PstI on the cloned gene fragment. The restriction maps of pMR5 and pMR6 were determined by comparative digestion of various endonucleases. The gene of GL-7-ACA acylase was localized on a 3.0kb fragment of B2-B3-HpaI from the studies on a serial subcloning. Expression of subclones pMR9, pMR10 and pMR11 in E. coli was compared. Higher yield of acylase was obtained when the gene fragment was placed downstream of the tac promoter. The expression of Pseudomonas gene in E. coli was also discussed. PMID- 1457718 TI - Significance of the 56th tyrosine on cytotoxic activity of tumor necrosis factor. AB - After using site-specific mutagenesis a conserved amino acid residue, the 56th tyrosine in human tumor necrosis was substituted by glutamine. The expression level of the mutant protein in E. coli did not changed significantly, however, its specific activity of the cytotoxicity on L929 cultural cells was decreased to 1/583 of that of the unmutant tumor necrosis factor. The results show that the 56th tyrosine residue or the region where tyrosine 56th located is important for the cytotoxic activity of tumor necrosis factor. PMID- 1457719 TI - The reverse DNA sequencing using Bst DNA polymerase. AB - The reverse DNA sequencing (RDS) [1] is a rapid method used to check the DNA sequences by sequencing them from the opposite orientation. Because the RDS is basically a double stranded sequencing, the quality of the sequence patterns so obtained generally is not as good as those obtained by the single stranded sequencing, and extra bands and higher background are produced more frequently. This paper shows that the RDS could now generate as good sequence patterns as those obtained by sequencing on the single stranded DNA template if Bst DNA polymerase instead of the conventional enzymes, such as the Klenow enzyme, was used in the RDS. Bst DNA polymerase is heat stable (optimum reaction temperature 65 degrees C) and has recently been successfully used in the conventional DNA sequencing. The RDS has recently been further simplified to meet the need of large DNA sequencing projects such as the human genome project. The combination of the simplified RDS and the use of Bst polymerase should be expected to facilitate greatly the work on sequence confirmation and correction. PMID- 1457720 TI - Electrofusion of protoplasts from Porphyra haitanensis and P. yezoensis thalli (Rhodophyta). AB - In this paper the electrofusion of protoplasts from P. haitanensis and P. yezoensis thalli by using an electrofusion instrument (Shimadzu Company, Japan) under different conditions of AC field, DC pulse, fusion buffer solutions and concentrations of protease are described. The results showed that the fusion rate could reach 21-31% by applying AC field of 30-35V for 25-30s and DC pulse of 300 350 V for 60 microseconds and in the presence of 3 mM Ca2+ and 3 mM Mg2+ in the fusion buffer. The pretreatment with protease had a positive effect on cell fusion. The fusion cells formed cell walls after 7 day's culture and grew into cell aggregates after 41 day's culture. PMID- 1457721 TI - Production of monoclonal antibody in hollow fiber culture system with serum-free medium. AB - Hybridoma cells 7E8, secreting mouse monoclonal antibody (McAb) IgG against potato virus X, were cultured in hollow fiber cell culture system (module VF-2) with serum-free medium 1640SFM. The maximum viable cell density was found to be 2.34 x 10(6) cells/ml that was 3.7 and 2.2 times as high as those achieved in spinner and static flask culture respectively. About 10,000ml of cell culture media had been collected in the cultural period of 42 days. The ELISA titer of the McAb in the media was about 1:20,000 that was 25 times as high as those attained from the cultures in either spinner or static flask. From 1,000ml of cell culture media, an amount of 51.2mg of 7E8 McAb IgG had been purified by 50% saturated ammonium sulfate precipitation and Sephadex G-200 chromatography. The average yield of McAb in the hollow fiber cell culture system was 12.3mg/day. The results of the study suggest that it is hopeful for hybridoma cell culture in the hollow fiber cell culture system with serum-free medium for McAb production on large-scale. PMID- 1457722 TI - Selection of strains capable of utilizing D-xylose and cellobiose to produce ethanol by electric field-induced protoplast fusion. AB - The protoplast fusion between Candida guilliermondii S208 (Arg-) and Saccharomyces cerevisiae 314 was induced by three pulses (18kV/cm, 10 microseconds duration) applied at an interval of 1 s with the model GH-401 Electric Induced Gene Transfer/Cell Fusion System. The frequency of appearance of prototrophic hybrids was 3.6 x 10(-3). Stable fusion products were obtained after continual subculture over 20 times on selected and unselected media. Comparative studies showed that the fusion products were real hybrids of both parents. Two fustants, F-106 and F-308, could ferment both D-xylose and cellobiose to ethanol. The ethanol production of F-106 in the media containing 2% D-xylose or 2% cellobiose were 3.1g/l and 1.05g/l, respectively. The ethanol production of F-308 in the above media were 0.2g/l and 2.8g/l, respectively. PMID- 1457723 TI - The suspension culture of Tripterygium wilfordii. AB - In suspension culturing of Tripterygium wilfordii, 18.4 mg/l of dry cells and 9.184 mg/l of diterpene-lactone compounds were obtained from 6,7-V liquid medium containing 1 mg/l NAA. Besides those within the cells, diterpene-lactone compounds were also found in the cultured liquid and the yield reached 30.16 43.14% of the total yield. The total yield of diterpene-lactone compounds in suspension culture (6,7-V medium containing 1 mg/l NAA) was 12.19 times as much as that in the roots of the original plant. In addition, 3 samples of diterpene lactone extracts from the suspension culture were found toxic to KB cells. Compared with those in solid culture, less incubation time was needed and more diterpene-lactone compounds were produced in suspension culture. PMID- 1457724 TI - Analysis of the effectiveness of proline substitutions and glycine replacements in increasing the stability of phage T4 lysozyme. AB - It was previously shown that the two replacements Gly 77-->Ala (G77A) and Ala 82- >Pro (A82P) increase the thermostability of phage T4 lysozyme at pH 6.5. Such replacements are presumed to restrict the degrees of freedom of the unfolded protein and so decrease the entropy of unfolding [B. W. Matthews, H. Nicholson, and W. J. Becktel (1987) Proceedings of the National Academy of Science USA Vol. 84, pp. 6663-6667]. To further test this approach, three additional replacements- G113A, K60P and A93P--have been constructed. On the basis of model building, each of these three replacements was judged to be less than optimal because it would tend to introduce unfavorable van der Waals contacts with neighboring parts of the protein. The presence of such contacts was verified for G113A and K60P by conformational adjustments seen in the crystal structures of these mutant proteins. In the case of G113A there are backbone conformational changes of 0.5 1.0 A in the short alpha-helix, 108-113, that includes the site of substitution. In the case of K60P the pyrrolidine ring shows evidence of strain. The thermal stability of each of the three variants at both pH 2.0 and pH 6.5 was found to be very close to that of wild-type lysozyme. The results suggest that the procedure used to predict sites for both Xaa-->Pro and Gly-->Ala is, in principle, correct. At the same time, the increase in stability expected from substitutions of this type is modest, and can easily be offset by strain associated with introduction of the alanine or proline. This means that the criteria used to select substitutions that will increase thermostability have to be stringent at least. In the case of T4 lysozyme this severely limits the number of sites. The analysis reveals a significant discrepancy between the conformational energy surface predicted for the residue preceding a proline and the conformations observed in crystal structures. PMID- 1457726 TI - DNA torsional dynamics by multifrequency phase fluorometry. AB - The time decay of the fluorescence polarization anisotropy of calf thymus DNA ethidium complexes is obtained from measurements with sine-modulated excitation employing the so-called multifrequency phase fluorometry. A torsional dynamics model developed by J. M. Schurr [(1984) Chemical Physics, Vol. 84, pp. 71-96] and translated into the frequency domain is found here to describe accurately DNA ethidium fluorescence data collected under modulated excitation. At a low dye/DNA ratio (1:400) the value of the DNA torsional constant (alpha = 4.63 +/- 0.2 10( 12) dyne cm) fitting the data agrees very well with the known values of alpha. When the measurements are extended to a higher ethidium/DNA ratio, energy transfer effects between intercalated dyes are observed. A theoretical prediction of the donor and acceptor dye contributions to the fluorescence polarization anisotropy is made here, taking into account also dye-dye distance distributions. PMID- 1457725 TI - Flexible-geometry conformational energy maps for the amino acid residue preceding a proline. AB - Previously calculated conformational energy maps suggest that the alpha-helical conformation for the residue preceding a proline is disfavored relative to the extended conformation by more than 7 kcal/mol. In known protein structures this conformation is observed, however, to occur for about 9% of all prolines. In addition, introduction or removal of prolines at theoretically unfavorable positions in proteins and peptides can have modest effects on stability and structure. To investigate the discrepancy between calculation and experiment, we have determined how the conformation of the proline affects the calculated energy. We have also explored the effect of bond length and bond angle relaxation on the conformational energy map. The conformational energy of the preceding residue is found to be unaffected by the conformation of the proline, but the effect of allowing covalent bond relaxation is dramatic. If bond lengths and angles, and dihedral angles within the pyrrolidine ring, are allowed to relax, a calculated energy difference between the alpha and beta conformations of 1.1 kcal/mol is obtained, in reasonable agreement with experiment. The detailed shape of the calculated energy surface is also in excellent agreement with the observed conformational distributions in known protein structures. PMID- 1457727 TI - Facilitated synthesis of peptaibols: alamethicin via enzymatic segment condensation. AB - We have used a combined chemical-enzymatic approach to facilitate the total synthesis of the 20-residue peptaibol, alamethicin. The 1-11 segment of alamethicin, having a C-terminal Gly, and the 12-20 segment, having an N-terminal Leu, were prepared by well-established chemical methods, and then coupled using papain to afford a 54% yield of alamethicin in straightforward fashion. In contrast to the reported chemical syntheses of alamethicin requiring side-chain protection at Glu,18 the papain-catalyzed coupling proceeded readily and selectively using a C-terminal segment having a free gamma-carboxyl group at this position. Several alamethicin partial sequences were obtained via enzymatic formation of the Gly11-Leu12 bond. The high efficiency of this route is illustrated by the enzymatic assembly of the 1-17 alamethicin fragment on a 400 mg scale in 62% yield. An alternative route to alamethicin through enzymatic formation of the Ala6-Gln7 bond was less successful because of a low yield in the final coupling. PMID- 1457728 TI - Quasielastic light scattering study of thermal excitations of F-actin solutions and of growth kinetics of actin filaments. AB - In the first part of this work we report quasielastic light scattering (QELS) studies of the internal dynamics of transient actin networks over a time range of 10(-6)-10(-2) s, scattering angles between zeta = 20 degrees and 150 degrees, and a concentration range of 0.015 (0.3) to 0.7 mg/mL (15 microM). We confirm our previous result that (1) the dynamic structure factor g(q,t) is determined by the thermally excited undulations of the actin filaments and (2) that the initial decay of g(q, t) scales as g(q, t) varies; is directly proportional to exp(-q alpha t) while the long time decay scales as g(q, t) varies; is directly proportional to exp [-(Aq alpha t) 2/3] with alpha = 2.75. The deviation of alpha from the theoretical value of alpha = 3 predicted for Rouse-Zimm chains is similar to that found for high molecular weight macromolecular solutions by QELS. A refined analysis of the dynamic structure factor showed that it can be interpreted in terms of three relaxation processes (besides the contribution of the residual monomer diffusion): (1) the dominant Rouse-Zimm dynamics, which comprises between 65 (at high concentrations) and 85% of the signal; (2) a fast relaxation process with a decay constant of gamma = 9 x 10(3) s-1, which contributes at all concentrations with the same amplitude; and (3) a nonexponential ultraslow contribution of the form g(us) varies; is directly proportional to exp [(-gamma ust)]1/4. The third contribution appears only at high concentrations and increases strongly with decreasing scattering angles. It is thus attributed to fluctuations of the mesh size of the transient actin network. In the second part we show that high sensitivity QELS may be applied to follow the actin polymerization process at low temperatures (10 degrees C). The apparent diffusion coefficient and the static scattering intensity of the actin filaments were determined as functions of polymerization time tpol. We show that the process consists of the rapid growth of a few filaments that become very long (approximately 10 microns; even at actin concentrations of 0.04 micrograms/mL) near the critical growth concentration of 0.012 micrograms/mL, as is expected for a growth process determined by nucleation. Finally, we studied actin networks polymerized in the presence of complexes of gelsolin with actin. By application of the CONTIN program we could determine the length distribution of the filaments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1457729 TI - Monte Carlo calculations of ion distributions surrounding the oligonucleotide d(ATATATATAT)2 in the B, A, and wrinkled D conformations. AB - We calculated the uni-univalent ion distributions around the oligonucleotide d(AT)5.d(AT)5 in the A, B and wrinkled D conformation using the Metropolis Monte Carlo method. All atoms were included in the oligonucleotide model with partial charges and hard sphere radii assigned to each atom. The univalent counter- and coions were modeled as hard spheres with radius 0.3 nm. The solvent was assigned a dielectric constant of 80, corresponding to a temperature of 298K. The counterion distribution surrounding each of the conformers and the distribution surrounding an impenetrable cylinder, were calculated for four salt concentrations. We found significant counterion density in the major groove of the A DNA while fewer counterions occupied the grooves of B DNA. In the wrinkled D DNA, where groove occupancy is sterically hindered, the ion distributions were identical to the distributions surrounding the impenetrable, cylindrical model. This suggests that excluded volume effects significantly influence the details of the ion distributions near the oligomer, while the detailed charge distributions of the oligomer affects the ion distributions only minimally. Although substantial variation in counterion density was observed near the oligomers of differing conformations, the total number of counterions located within a cylinder surrounding the oligomer bounded radially by 2.4 nm was independent of the conformation of the oligomer. Therefore, for this model system, the local univalent counterion distributions are extremely sensitive to the geometry of the oligonucleotide whereas the extent of neutralization of the oligoanion is insensitive to the conformation of the oligomer. PMID- 1457730 TI - A synthetic analogue for the active site of plant-type ferredoxin: two different coordination isomers by a four-cys-containing [20]-peptide. AB - The (Fe2S2)2+ complex of an artificial 20-peptide ligand, Ac-Pro-Tyr-Ser-Cys-Arg Ala-Gly-Ala-Cys-Ser-Thr-Cys-Ala-Gly-Pro-Leu-Leu-T hr-Cys- Val-NH2, containing an invariant Cys-A-B-C-D-Cys-X-Y-Cys (A, B, C, D, X, Y = amino acid residues) fragment of plant-type ferredoxins was synthesized by a ligand exchange method with [Fe2S2(S-t-Bu)4]2-. 1H-nmr spectroscopic and electrochemical data of the complex indicate the presence of two coordination isomers. One of them having a Cys-X-Y-Cys bridging coordination to the two Fe(III) ions, has the (Fe2S2)2+ core environment similar to those of the denatured plant-type ferredoxins and exhibits a positive shifted redox potential at -0.64 V vs saturated colonel electrode (SCE) in N,N-dimethylformamide (DMF). Another isomer with the Cys-A-B-C-D-Cys bridging coordination shows a negative redox potential at -0.96 V vs SCE in DMF. PMID- 1457731 TI - Peptide hormone-membrane interactions: the aggregational and conformational state of lipo-gastrin derivatives and their receptor binding affinity. AB - The (2RS)-1,2-dipalmitoyl-3-mercaptoglycerol/-, (2RS)-1,2-dimyristoyl-3 mercaptoglycerol/-, and (2RS)-1-myristoyl-2-palmitoyl-3-mercaptoglycerol/maleoyl bet a-alanyl- [Nle15]-human-gastrin-(2-17) adducts were prepared as lipo-gastrin derivatives of explicitly primary amphiphilic properties. As representative of this class of lipo-gastrins, the dimyristoyl derivative has been thoroughly characterized in its aggregational state since, among the three compounds, theoretically it should exhibit the lowest degree of lipid character. It aggregates in aqueous solution to form monodispersed unilamellar spherical vesicles with dislocation of the peptide moiety at the bilayer surface in predominantly unordered structure. The liposomes are remarkably stable toward solubilization with trifluoroethanol and toward vesicle to micelle transition with neutral and negatively charged surfactants even above their critical micellar concentrations. Asymmetric fusion with the detergent micelles induces polydispersion of the liposomes in terms of shape and size without affecting in significant manner the mode of display of the gastrin portions at the bilayer surface. Only the positively charged hexadecyltrimethylammonium hydroxide provokes the collapse of the vesicles into mixed micelles with concomitant altered dislocation of the gastrin-peptide in the new aggregational state. Despite the lipid properties of the gastrin derivatives, i.e., formation of liposomes, they retain remarkable receptor affinities (IC50 = 1.5 x 10(-9) M for myristoyl-palmitoyl-gastrin, IC50 = 2.0 x 10(-9) M for di-myristoyl-gastrin and IC50 = 3.1 x 10(-9) M for di-palmitoyl-gastrin vs IC50 = 2.8 x 10(-10) M for Nle15-gastrin). Since the displacement of radiolabeled Nle15-gastrin from rat pancreatic acinar cell line membrane preparations by both the parent gastrin hormone and the three lipo-gastrins occurs in parallel manner, the data support a mechanism of receptor occupancy via accumulation of the gastrins at the membrane surface and their two-dimensional diffusion to the target receptor. Thereby the differentiated decrease of affinity in function of fatty acid chain length has to be attributed to the energetically more or less favored transfer of the monomers from the donor vesicles to the acceptor membranes. Moreover, according to this model migration of the lipo-gastrins with their interdigitating di-fatty-acyl moieties should be delayed, again in lipid structure-dependent manner, in comparison to the parent gastrin molecule, which is free to float in the membrane interfacial phase. PMID- 1457732 TI - Conformational perturbation of the anticancer nucleotide arabinosylcytosine on Z DNA: molecular structure of (araC-dG)3 at 1.3 A resolution. AB - The left-handed Z-DNA structure of an araC-containing (where araC stands for arabinosylcytosine) hexamer, (araC-dG)3, has been solved by x-ray diffraction analysis at 1.3 A resolution. This hexamer was crystallized in the hexagonal P6(5)22 (a = b = 17.96 A, c = 43.22 A) space group in which the hexamers have statistically disordered packing arrangement along the 6(5) screw axis, yet the crystals diffract x-rays to high resolution. Its structure has been refined by the constrained least square refinement to a final R factor of 0.287 using 737 [> 3.0 sigma(F)] observed reflections. The asymmetric unit of the unit cell contains only a dinucleotide, 5'-p (araC)p(dG). The overall conformation resembles that of the canonical Z-DNA, but with some differences in details. The O2' hydroxyl groups of the araC residues form intramolecular hydrogen bonds with N2 of the 5' guanine residues. In the deep groove of Z-DNA, these hydroxy groups replace the bridging water molecules that stabilize the guanine in the syn conformation. The results reinforce the earlier observation made by the structural analysis of another hexamer, d(CG[araC]GCG), with a mono-substitution of araC [M.-K. Teng, Y. C. Liaw, G. A. van der Marel, J. H. van Boom, and A. H.-J. Wang (1989) Biochemistry, vol. 28, pp. 4923-4928]. These two structures show that araC residue can be incorporated readily into the Z structure and probably facilitates the B to Z transition, as supported by uv absorption spectroscopic studies in a number of araC-containing oligonucleotides. The potential biological roles of the araC-modified Z-DNA are discussed. PMID- 1457733 TI - Kinetics of folding and unfolding of beta beta-tropomyosin. AB - The kinetics of folding from random coils to two-chain coiled coils of beta beta tropomyosin was studied by stopped-flow CD (SFCD) in the backbone region (222 nm). Two species were studied: the reduced form and the doubly disulfide cross linked form. The proteins were totally unfolded in 6M urea-saline buffer, then refolded by tenfold dilution into benign buffer. In the refolding medium, they spontaneously recover the two-chain coiled-coil structure. Reduced beta beta refolds in at least two stages: one or more fast phases (< 0.04 s), in which an intermediate with 71% of the equilibrium ellipticity forms, followed by a slower time-resolvable phase that completes the folding. The slow phase is first order, signifying that dimerization occurs in the fast phase. The time constant of the slow phase is 2 s at 20 degrees C and requires activation parameters of delta S not equal to = -7 +/- 0.3 cal/mol.K, delta H not equal to = 15 +/- 1 kcal/mol. These results are very similar to those previously found for the reduced genetic variant alpha alpha-tropomyosin. In contrast, refolding of doubly disulfide cross linked beta beta is complete within the dead time (< 0.04 s), whereas the singly cross-linked alpha alpha species also displays a slow phase. The opposite process, unfolding reduced beta beta from the coiled-coil state, is complete within the dead time, as in the alpha alpha variant. PMID- 1457734 TI - Alpha-helix to random coil transitions: interpretation of the CD in the region of linear temperature dependence. PMID- 1457735 TI - The antigen-antibody interaction algebraically interpreted as a relational process. AB - The antigen-antibody interaction occurring previous to the triggering of the immunological response is analyzed as a relational process in terms of lattices. Accordingly, this process is expressed as a lattice belonging to a pseudo-Boolean algebraic variety. The Heyting arrow operation, which appears in this kind of algebra, is used to analyze behaviors between non-comparable biological states expressed by the lattice. The resulting states coming from the arrows are connected with the influence of increasing and decreasing energies involved in the linking process. PMID- 1457736 TI - The uncertainty principle as an evolutionary engine. AB - Heisenberg's uncertainty principle in quantum mechanics underlies the genesis of evolutionary variability. When the uncertainty principle is coupled with the incontrovertible principle of the conservation of energy and material resources, there appears an uncertainty relationship between local fluctuations in the quantities to be conserved on a global scale and the rate of their local variation. Since the local fluctuations are accompanied by the non-vanishing rate of variation because of the uncertainty relationship, they generate subsequent fluctuations. Generativity latent in the uncertainty relationship is non-random and ubiquitous all through various evolutionary stages from abiotic synthesis of monomers and polymers up to the emergence of behavior-induced variability of organisms. PMID- 1457737 TI - Periodical changes of amino acid reactivity within the genetic code. AB - Enthalpies (delta H++) and entropies (delta S++) of activation for the reaction of 18 N'-hydroxysuccinimide esters of N-protected proteinaceous amino acids with p-anisidine were measured and free enthalpies of activation (delta G++) at 25 degrees C were calculated on this basis. A regular correlation between delta G++s and the corresponding amino acid codons was found. To obtain this correlation all the codons had to be arranged in a closed ring in which the consecutive codons were connected by one-step mutational changes. One-step mutations appeared as a regular series: 2,3,3,3,1,3,3,3,1,3,3,3,1,3,3,3,2,3,3,3. (the numbers denote a codon position in which a change took place). There were three such 'one-step mutation periods' in the ring, each containing 20 codons (in each block of 16 codons with A, U and C, in the central position and 4 codons containing G in the central position). The end of the third period (UG) and the beginning of the first period were bridged by the four codons of glycine with G in the second position. The values of delta G++ change similarly in each period, increasing upon approaching Lys, Pro, and Ile. The periodical relation between the chemical reactivities of the coded amino acids (reflected by delta G++s) and the structure of their codons could be of importance for the origin of the genetic code i.e. for selection of proper codons for the definite amino acids. PMID- 1457738 TI - Enzymes as molecular automata: a reflection on some numerical and philosophical aspects of the hypothesis. AB - Enzymes, by means of their properties of specific recognition and allosteric modulation, are able to integrate many separate processes into systemic units with coherent functions; in a sense, they have to be considered as the true organizers of the cytoplasmic processes. In this respect, the present article describes a simple model, based on binary variables and automata theory, which simulates the basic regulatory performance of the modulated enzyme. The model admits a variety of modifications and improvements; it also suggests some original lines of thought on which to reflect about the organization and collective phenomena of the networks of enzymes. In discussing the connection of this 'molecular automata' hypothesis with other areas of present-day theoretical biology, a fertile panorama of initiatives appear. A special partnership between Information Science (computation) and Biology is developing. PMID- 1457739 TI - Fibronectin promotes lung colony formation in the mouse by B16 melanoma cells spheroids. AB - By microscopical observation and using an original method of automatic image analysis, we studied on histological sections the rate of lung colony formation after intravenous injection into the mouse of B16 melanoma cells previously cultivated in vitro as pure or mixed spheroids (B16 + 3T3 fibroblasts). The preincubation in vitro of pure spheroids with fibronectin significantly increased the percentages of lung section area occupied by tumors and the relative number of internal lung colonies. This effect of fibronectin was even more obvious when mixed spheroids were injected. PMID- 1457740 TI - Bacterial mutagenicity of extracts of the baked and raw Agaricus bisporus mushroom. AB - Aqueous extracts of baked and raw Agaricus bisporus (AB) mushroom were tested for mutagenic activity in Salmonella typhimurium strains TA1535 and TA1537. The extracts were studied with and without metabolic activation by Aroclor-induced rat liver S9 mix. The extracts of the baked and raw AB exhibited a dose related mutagenic activity with and without activation in strain TA1535. Similar findings were obtained in strain TA1537, although the net revertant values were of lower magnitude. Because humans mainly consume the cultivated mushroom AB in baked form, the implications of the findings are self-evident. PMID- 1457741 TI - Anti-influenza virus activity of a lignin fraction from cone of Pinus parviflora Sieb. et Zucc. AB - When mice were inoculated intranasally or intracerebrally with lethal doses of influenza virus A/WSN/33, most died within 12 days. However, the infectivity of virus that had been preincubated with a lignin prepared from cones of Pinus parviflora Sieb. et Zucc. (PC-Fr. VI) was significantly reduced. Intraperitoneal or oral administration of PC-Fr. VI, prior to virus inoculation, slightly increased the survival ratio of the infected mice. Experiments using radiolabeled PC-Fr. VI revealed that this fraction effectively binds to virions as well as to cultured cells. These data suggest that PC-Fr. VI either inactivates the virus or induces the anti-viral state in cells by binding to virions or cells. PMID- 1457742 TI - Effects of a human urinary kininogenase (SK-827) on cerebral microcirculation after glass bead-induced cerebral embolism in rabbits. AB - The pharmacological effects of a human urinary kininogenase (SK-827) on the cerebral microcirculation were studied intravital-microscopically in a rabbit with cerebral microvessel injury induced by glass bead injection into an internal carotid artery. Intravenous administration of SK-827 dilated pial arteries of the brain and increased cerebral hemoglobin content (IHb). SK-827 tended to dilate smaller arterioles more markedly than larger arterioles, and larger arterioles than small arteries. SK-827 appeared to have a vasodilating effects qualitatively different from those of nicardipine and CDP-choline. Findings obtained by concurrent hematological and biochemical examinations also suggested its beneficial effects on the function of platelets and erythrocytes. PMID- 1457744 TI - Changes in the chicken bursa of Fabricius and immune response after treatment with melatonin. AB - Since melatonin causes considerable reduction in the thymic weight of chickens, the aim of the present study was to find out whether the bursa of Fabricius and the immune response are also affected by this substance. The results show that melatonin also acts on the bursa of Fabricius depending upon the administration route. When injected subcutaneously it does not reduce bursal weight and the histological pattern does not change, while primary and secondary immune responses are significantly lowered. When melatonin is introduced into the bursa, it causes a considerable decrease in bursal weight and the histological pattern is greatly modified. A significant reduction in antibody production is observed involving the primary immune response alone. Transmission electronic microscopy seems to show that melatonin affects the reticulo-epithelial (REp) cells. PMID- 1457743 TI - Suppressive effect of vitamin E on lipid peroxidation in halothane-administered guinea pig liver. AB - The effect of vitamin E on halothane-induced liver damage was studied in guinea pig halothane hepatitis. Twenty animals were divided into 3 groups, consisting of a control group, a halothane group and a vitamin E + halothane (H) group. The animals in the control group (n = 6) were allowed to inhale air only. The animals in the halothane group (n = 6) and the vitamin E + H group (n = 8) were allowed to inhale 1% halothane with air. Animals in the vitamin E + H group were additionally injected with 30 mg kg-1 of vitamin E 30 minutes prior to inhalation of halothane. Blood was aspirated from the heart immediately after sacrificing to measure the serum activity of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT). A microsomal suspension was prepared from the excised liver. Then the amount of thiobarbituric acid (TBA) reactive products in the microsomes were measured. The amount of tissue TBA-reactive products was increased by inhalation of halothane. The increase in the amount of TBA-reactive product was inhibited by the administration of vitamin E. The serum GPT activity was increased by halothane inhalation. Increased serum GOT and GPT activity were inhibited by the administration of vitamin E. These results demonstrated that vitamin E suppressed halothane-induced liver damage in the guinea pig by inhibiting lipid peroxidation. PMID- 1457745 TI - The high resolution RBG-banded karyotype of Felis catus. PMID- 1457746 TI - Thirty day genotoxicity study of an organophosphate insecticide, monocrotophos, in a chick in vivo test system. AB - The genotoxicity of an organophosphate insecticide, monocrotophos, was evaluated upon chronic exposure in a chick in vivo test system employing micronucleus bioassay. In this study the animals were treated once daily for 30 days. The induced frequency of micronuclei in the erythrocytes of both bone marrow (BM) and peripheral blood (PB) were significantly higher than the respective control values. Weekly recording of the body weight of treated and control groups did not reveal any significant effect of the chemical on the general growth rate. The present results revealed the genotoxic potential of monocrotophos and also substantiate our earlier suggestion regarding the suitability of the chick in vivo test system to screen environmental abuses for mutagenicity. PMID- 1457747 TI - Monocyte release and plasma levels of interleukin-6 in patients irradiated for cancer. AB - Interleukin-6 (IL-6) release from purified blood monocytes was determined in patients with breast cancer or prostatic cancer before and after radiation treatment (Rx). Plasma levels of IL-6 and neopterin were also determined. Spontaneous IL-6 release in vitro was higher in breast than in prostatic cancer or in controls. Strong lipopolysaccharide (LPS)-induced cellular IL-6 release was detected in breast cancer and controls but was subnormal in prostatic cancer. Addition of indomethacin to cultures had no effect on IL-6 release. Rx generally increased levels of in vitro released IL-6 and raised LPS-stimulated IL-6 secretion in prostatic cancer to normal. Plasma levels of IL-6 were lower in breast than in prostatic cancer or controls. Rx resulted in a tendency towards raised levels in both patient groups suggestive of monocyte activation. In accordance with this, plasma levels of neopterin, which were normal before treatment, increased in prostatic cancer patients after Rx. Taken together, the results of this study indicate that monocyte release as well as plasma levels of IL-6 are affected by the malignant state as well as by radiation treatment. In view of the antiproliferative effects of IL-6, the findings may have bearing on the pathogenesis and treatment of malignant disease. PMID- 1457748 TI - Intraperitoneal injection of dipyridamole increases the life span of tumor bearing mice treated with fluorouracil. AB - This study was carried out to investigate the effect of the Fluorouracil (5-FU) and Dipyridamole (DP) combination on the growth of P388 murine lymphoid neoplasms. The first stage was to determine the lethal dose (LD 50) for each compound (5-FU, DP) to normal B6D2F1 mice after intraperitoneal (i.p.) injection. The LD 50 were 700 and 54 mg/kg for DP and 5-FU respectively. B6D2F1 mice bearing P388 ascitic tumors and receiving a 4-day schedule of 5-FU (2 mg/kg/day) with DP (100 mg/kg/day) 1 hr before each 5-FU dose were studied. DP was found to lower significantly (p < 0.0001) the mortality of 5-FU in tumor bearing mice by nearly 2.5 fold. This study aims at defining the best dose combination of intraperitoneal injection of 5-FU in conjunction with DP. These data allow a prospective evaluation of 4-day, i.p. 5-FU and DP with an increase of life span without toxic death. PMID- 1457749 TI - Histopathological changes in rat pancreas after fasting and cassava feeding. AB - Histopathological changes in rat pancreas were induced by cyclic periods of experimental malnutrition or by cassava (manioc) feeding for 11 weeks. Decline of body weight was correlated with decrease in testicular fat pad weight as a measure of body fat stores. A marked decrease in pancreatic weight in the cassava fed group was correlated with shrinkage of acinar structures and degenerative features in exocrine pancreas. In the malnutrition group vacuolisation and loss of tissue architecture were observed in some parts of the organ. No signs of ductal obstruction as a tentative cause of pancreatic pathology after malnutrition could be detected. Loss of islets tissue was occasionally seen in degenerative areas. It is concluded that histopathological changes in exocrine pancreas result from malnutrition and cassava feeding differentially and precede ultimate degenerative processes of pancreas endocrine tissue. Tropical malnutrition type diabetes and low protein related diabetes may in their etiology be different entities, but may coincide in practice and aggravate each other to yield severe and irreversible morbidity. PMID- 1457751 TI - Hypertension associated with diabetes mellitus--past and future. PMID- 1457750 TI - Improved efficacy of doxorubicin by simultaneous treatment with interferon-gamma and interleukin-2. AB - Doxorubicin (DOX) is a potent anticancer agent active against a wide range of human neoplasms, yet, as is characteristic of most chemotherapeutics, the treatment of cancer with DOX alone has met with only limited success. This study was designed to investigate the possibility that the therapeutic potential of DOX could be enhanced by combination with one or more biological response modifiers. Segments (1mm3) of a transplantable colonic adenocarcinoma were implanted into the hind limbs of male WAG rats (200-250g). Serial tumour measurements were taken 3 x weekly throughout the 4 week experimental period by measuring the longest and perpendicular lengths with calibrated calipers. All drug administration was via a chronic indwelling jugular catheter, commencing 12 days after tumour implant, with control animals receiving physiological saline. Treatment of animals with DOX (4.5mg/kg as a 15 minute i.v. infusion), interferon gamma (IFN-gamma) (5 x 10(5) U/kg/day bolus i.v. for 5 days) or interleukin-2 (IL-2) (1 x 10(5)U/rat/day continuous i.v. infusion for 5 days) retarded tumour growth by approximately 30% by the completion of the study period (P < 0.001). The combined administration of IFN-gamma with DOX did not significantly alter the antitumour activity of either DOX or IFN-gamma. Concurrent administration of IL-2 with DOX also showed this treatment to have no therapeutic activity over that achievable with either agent alone. However, treatment of animals with IL-2, IFN-gamma and DOX resulted in a significant increase in tumour growth inhibition compared to DOX with either single cytokine (P < 0.001) and this was achieved without any apparent increases in the gross toxicity of DOX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457752 TI - Coronary artery disease is the major determinant of excess mortality in patients with insulin-dependent diabetes mellitus and persistent proteinuria. AB - The goal of this review was to assess the magnitude of coronary artery disease (CAD) mortality and its determinants in insulin-dependent diabetes mellitus (IDDM) patients with persistent proteinuria. By reanalyzing data from two previously published studies of patients with nephropathy, it was found that these patients had extremely high CAD mortality rates in comparison with IDDM patients without proteinuria, but only after the age of 35 yr. In addition, the risk of CAD death was associated with high serum cholesterol levels but was unrelated to systemic blood pressure, smoking habits, and obesity. Further studies of the determinants of CAD in patients with IDDM and proteinuria are urgently needed. Except for efforts to lower serum cholesterol, it is not known whether any other measure can be undertaken to reduce the extremely high mortality due to CAD that afflicts IDDM patients with persistent proteinuria, in particular those patients whose renal failure might have been "successfully" postponed by antihypertensive therapy. PMID- 1457753 TI - Cost-effectiveness of screening and early treatment of nephropathy in patients with insulin-dependent diabetes mellitus. AB - Studies have demonstrated that "antihypertensive" treatment with angiotensin converting enzyme inhibitors (ACEI) may retard the progress of nephropathy in patients with insulin-dependent diabetes mellitus. To obtain an indication of the potential effect of ACEI treatment and as a guide to future research, the effects of screening and early ACEI treatment programs were estimated using cost effectiveness models. The preliminary analysis suggests that the early treatment of insulin-dependent diabetes mellitus patients with ACEI is likely to be a very cost-effective use of health care resources. The cost-effectiveness ratio for screening and treatment at the stage of microalbuminuria ($7,900 to $16,500 per year of life saved) compares favorably with those of other medical life-saving interventions. Less-aggressive programs (screening followed by treatment at the stage of proteinuria) would improve life expectancy to a lesser extent but could save net health care costs as well as years of life. Although more exact and comprehensive cost-effectiveness analysis must await clinical trials, these illustrative results demonstrate the range of cost-effectiveness that can be expected from these programs and identify data needed for more decisive policy conclusions. PMID- 1457754 TI - Hypertension and the development of complications in patients with non-insulin dependent diabetes mellitus in Japan. AB - Hypertension is a very frequent condition in individuals with non-insulin dependent diabetes mellitus (NIDDM) in Japan and has affected the occurrence of late diabetic complications, especially stroke and nephropathy. Despite similar characteristics of hypertension among Japanese and white patients, the effect of hypertension on the development of coronary artery disease (CAD) in these two populations is strikingly different. In white NIDDM patients, hypertension is one of the major risk factors for the development of CAD. However, CAD is an infrequent complication in NIDDM patients in Japan, even though they have hypertension, lipid abnormalities, and renal complications. PMID- 1457755 TI - Hypertension and coronary artery disease in non-insulin dependent diabetes--cause and effect? AB - There is a log-linear increase in the risk of coronary heart disease with elevation of levels of blood pressure. Allowing for the phenomenon of regression dilution bias, this corresponds to around a 20 to 25% increase in risk for each 5 to 6 mm Hg elevation in usual diastolic blood pressure. In diabetic subjects, a similar relationship occurs, but of somewhat lesser degree. Recent overviews of therapy suggest that in nondiabetics, reducing blood pressure reverses around 50% of the excess coronary heart disease risk, but this has not yet been conclusively shown in patients with diabetes. The reduction in risk with therapy is a prerequisite to defining the antecedent as a causal influence on outcome, but it is as likely that the incomplete reversibility of excess risk represents other pathways of connection between hypertension and coronary heart disease as a consequent of iatrogenic effects of current treatments. Several alternative mechanisms are outlined, and the suggestion is made that only in the context of randomized controlled studies could the possible benefits on coronary heart disease of agents influencing such mechanisms be assessed. PMID- 1457756 TI - Pharmacologic therapy of mild to moderate hypertension: possible generalizability to diabetics. AB - This article reviews the evidence on pharmacologic therapy of hypertension in reducing morbidity and mortality from stroke and coronary heart disease (CHD) and considers the possible generalizability of these findings to diabetics. For malignant hypertension, benefits are large and obvious from uncontrolled case series. For severe hypertension, conclusive benefits have been shown in several randomized trials. For mild to moderate hypertension, however, it is necessary to consider meta-analyses of all individual trials. The most comprehensive of these shows reductions of 42% for total stroke (95% Cl, -33 to -50%; P < 0.0001) and 14% for all CHD (95% Cl, -4 to -22%; P < 0.01). The applicability to diabetics is unclear because they were excluded from most of the trials. The Hypertension Detection and Follow-Up Program included diabetics and reported subgroup analyses. The reduction in mortality among the actively treated diabetics of 5% was less than the 17% achieved in nondiabetics. It is unclear, however, whether the mortality reductions are truly different or reflect the play of chance. Because of the higher incidence of CHD events among diabetics with hypertension, a similar relative benefit would result in a much greater absolute risk reduction. Further, the drugs used adversely affect lipid and glucose metabolism. New antihypertensive drugs without these side effects may further improve the risk-to-benefit ratio of antihypertensive treatment, especially in diabetics, who are at a several-fold absolute increased risk or cardiovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457757 TI - Identifying genetic determinants in human essential hypertension. AB - Genetic factors play an important role in the pathophysiology of human essential hypertension. The remarkable success of molecular genetic techniques in identifying the basis for single gene disorders at the DNA level has encouraged investigators to apply similar techniques in an attempt to identify blood pressure genes. In contrast to single gene disorders, however, the study of blood pressure is complicated by its quantitative, complex, heterogeneous, and polygenic nature. This article examines current methods and strategies for identifying genetic determinants in human hypertension. The availability of highly polymorphic markers, the advances in quantitative trait analysis, and the mapping of blood pressure-determining genes in a polygenic rat model of hypertension suggest that molecular genetic research in human hypertension has come of age. PMID- 1457758 TI - Predisposition to essential hypertension and the development of diabetic nephropathy. AB - Only a subset of insulin-dependent diabetic patients are at risk of developing nephropathy. Prospective studies of uncomplicated insulin-dependent diabetic cohorts have shown that a rise in systemic arterial pressure is a concomitant feature of the progression to early nephropathy. The development of hypertension is an integral feature of established nephropathy in diabetes, and its amelioration retards the progression of disease and may improve overall mortality. Family studies have suggested that nondiabetic parents of insulin dependent diabetic patients with nephropathy have a greater prevalence of hypertension, and in certain groups of non-insulin dependent patients, it has been found that the blood pressure before the onset of diabetes correlates with the development of nephropathy after the onset of diabetes. These results indicate that a propensity to hypertension may be part of the genetic predisposition to nephropathy. This contention is further supported by the finding that a raised erythrocyte sodium-lithium countertransport, a biochemical marker of hypertension and cardiovascular disease whose activity is largely genetically determined, occurs with greater frequency in proteinuric diabetic patients and their nondiabetic parents than in those diabetic patients without nephropathy and their parents. Recent family studies have also shown that a family history of cardiovascular disease significantly increases the risk of nephropathy by up to three-fold in insulin-dependent diabetes. It is suggested that the cardiorenal complications of diabetes mellitus may be linked to reduced insulin sensitivity, which itself is associated with hypertension, raised sodium lithium countertransport rates, and cardiovascular disease. PMID- 1457759 TI - Predisposition to essential hypertension and renal hemodynamics in recent-onset insulin-dependent diabetic patients. AB - The offspring of essential hypertensive parents have been found to exhibit abnormalities in renal hemodynamics and sodium handling before the eventual occurrence of hypertension. The reported abnormalities represent a wide spectrum of changes including increased GFR, normal or decreased RPF, slight increase in blood pressure (although within the normal range), and an exaggerated natriuresis response to a sodium load. The heterogeneity of these abnormalities may reflect the specific conditions of the studies, the lability of the changes, or different subgroups of subjects with genetic predisposition to essential hypertension. Several lines of evidence have suggested a relationship between hypertension and the development of diabetic nephropathy in insulin-dependent diabetics. This laboratory has found that recent-onset insulin-dependent diabetics can exhibit renal hemodynamics abnormalities very early in the course of diabetes according to a positive or negative family history of essential hypertension. These changes include increased GFR and mean arterial pressure, but no differences in renal sodium and lithium handling in diabetics with a genetic predisposition to essential hypertension. In addition, diabetics with a positive family history of essential hypertension exhibited a more-marked vasodilative response to an acute interruption of the renin-angiotensin system, further suggesting inadequate angiotensin modulation of renal vascular tone. The significance of these abnormalities in relation to the development of diabetic nephropathy requires further investigation. PMID- 1457760 TI - Sodium activation kinetics of red blood cell Na+/Li+ countertransport in diabetes: methodology and controversy. AB - Although many studies report an elevated Vmax of red blood cell Na/Li countertransport (CTT) activity in patients with insulin-dependent diabetes mellitus (IDDM) complicated by renal disease, divergent reports exist. This article reviews the technical issues and selection criteria that fuel this controversy. In addition, new studies from this laboratory indicate that insulin in vitro and in the nonfasted state modulate CTT activity and may contribute to the discrepant findings. Incubation of red blood cells from fasted controls with physiologic concentrations of insulin induced a twofold increase in the Km for external Na+. Similarly, Na+ activation kinetics of Li+ efflux showed saturation between 50 and 150 mM Na+ in fasted controls whereas saturation, postprandially, occurred between 100 and 150 mM Na+ as a result of an increase in Km. To clarify the role of prandial status on the measurement of Na+/Li+ CTT activity in diabetes, Na+ activation kinetics were investigated in 34 nonfasting patients with IDDM. Li+ efflux was fully saturated between 80 and 150 mM Na+ in the normoalbuminuric subjects (N = 22), whereas saturation occurred between 150 and 280 mM Na+ in the patients with diabetic nephropathy (N = 14). Patients with nephropathy have higher values of Km for Na+ than do the patients free of renal complications (86 +/- 9.5 versus 41.3 +/- 3.4 mM Na+, respectively; P < 0.000012). The higher Km prevented complete saturation of Li+ efflux at 150 mM extracellular Na+ concentration and contributed to the underestimation of Vmax at 150 mM Na+ selectively in persons with renal complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457761 TI - Close relationship between microalbuminuria and insulin resistance in essential hypertension and non-insulin dependent diabetes mellitus. AB - The aim of this study was to investigate the relationships among insulin resistance and albumin excretion rate in 25 nondiabetic patients with essential hypertension and in 28 patients with non-insulin dependent diabetes mellitus (NIDDM). Two groups of healthy subjects matched for age, sex, and weight served as controls. Patients with essential hypertension were divided into two subgroups: without (H1) and with (H2) microalbuminuria. Diabetic patients were divided into four subgroups: those with normoalbuminuria without (NIDDM1) and with (NIDDM2) hypertension and those with microalbuminuria without (NIDDM3) and with (NIDDM4) hypertension. Whole-body glucose utilization during euglycemic hyperinsulinemic clamp (40 mU/m2/min insulin infusion) was calculated by tracer dilution techniques (6,6 2H2 glucose tracer continuous infusion) and was significantly lower in hypertensives with microalbuminuria than in those without (H2 versus H1 versus controls: 3.41 +/- 0.51 versus 6.52 +/- 0.62 versus 7.03 +/- 0.48 mg/kg/min; mean +/- SE). Whole-body glucose utilization in NIDDM patients- NIDDM4 versus NIDDM3 versus NIDDM2 versus NIDDM1 versus controls--was: 1.86 +/- 0.31 versus 2.21 +/- 0.39 versus 2.01 +/- 0.40 versus 5.98 +/- 0.77 versus 5.52 +/- 0.92 mg/kg/min (mean +/- SE). Whereas the first three subgroups did not differ among themselves, they had significantly lower glucose utilization than did the normotensive NIDDM1 patients without microalbuminuria and nondiabetic controls (P < 0.01). Hypertensives with microalbuminuria had higher Vmax of sodium-lithium countertransport (Na/Li CTT) in red blood cells than did both hypertensives without microalbuminuria and controls. It was also observed that NIDDM patients with microalbuminuria had higher Vmax of Na/Li CTT than did NIDDM patients without microalbuminuria and controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457762 TI - Normal blood pressure in patients with insulinoma despite hyperinsulinemia and insulin resistance. AB - This article examines the relationship between blood pressure and serum insulin patients with endogenous hyperinsulinemia due to insulinomas. The hypothesis that hyperinsulinemia is an independent causal factor in the development of essential hypertension in this patient population was investigated. Inappropriately high plasma concentrations of insulin and proinsulin were found in these patients; however, their blood pressure levels did not differ from those of normal control subjects. Moreover, the surgical removal of the insulinomas did not reduce their blood pressure. Therefore, these findings argue against the hypothesis that hyperinsulinemia is an independent causal factor in the development of essential hypertension in humans. PMID- 1457763 TI - Alterations in insulin receptor and substrate phosphorylation in hypertensive rats. AB - Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kd (insulin receptor substrate 1 or IRS 1) in most cell types. Tyrosine phosphorylation of insulin receptor and of IRS-1 have been implicated in insulin signal transmission based on studies with insulin receptor mutants. In the study presented here, the levels and phosphorylation state of the insulin receptor and IRS-1 in liver and muscle after insulin stimulation in vivo have been examined in spontaneously hypertensive rats (SHR) by immunoblotting with antipeptide antibodies to insulin receptor and IRS-1 and antiphosphotyrosine antibodies. It was found that the levels of insulin receptor and IRS-1 protein in liver and muscle are similar in controls (Wistar-Kyoto rats) and SHR. By contrast, there is a decrease in autophosphorylation in the liver and muscle of SHR and a parallel decrease in phosphorylation of IRS-1. These data indicate that reduced insulin receptor kinase activity and reduced substrate phosphorylation may play an important role in the impaired insulin action in the hypertensive rat. PMID- 1457764 TI - Cellular ions in hypertension, insulin resistance, obesity, and diabetes: a unifying theme. AB - The clinical linkage of hypertensive cardiovascular disease, left ventricular hypertrophy, and accelerated atherosclerosis with a spectrum of metabolic disturbances including peripheral insulin resistance, hyperinsulinemia, obesity, and frank non-insulin dependent diabetes mellitus, has been increasingly appreciated. However, the underlying biologic basis mediating this clinical association remains unclear. Nuclear magnetic resonance techniques have been used to measure various intracellular ion species in human erythrocytes and have found that common, shared intracellular abnormalities of cytosolic free calcium, free magnesium, and pH occur in each of these clinical syndromes. Specifically, essential hypertension is characterized by higher fasting free cytosolic calcium concentrations and reciprocally lower intracellular free magnesium and pH levels compared with those of normotensive control subjects. Furthermore, for all subjects, free calcium and free magnesium levels were closely related both to the left ventricular mass and to the degree of insulin resistance present. Moreover, these same intracellular ionic lesions were found in normotensive obese and/or non-insulin diabetic individuals. Last, evidence has recently been provided that the cardiovascular consequences of increased dietary sugar and salt intake may well be determined by their concurrent influence on cellular ion metabolism. These data led to a hypothesis for a central role for altered cellular ion homeostasis in mediating the clinical linkage of cardiovascular and metabolic disease. According to this ionic hypothesis, essential hypertension, non-insulin dependent diabetes, and their frequently associated features of obesity, left ventricular hypertrophy, and accelerated atherosclerosis all derive from and reflect different clinical manifestations of the same underlying cellular lesion, characterized at least in part by elevated cytosolic free calcium and suppressed free magnesium levels. PMID- 1457765 TI - Molecular genetic approaches to the identification of genes involved in the development of nephropathy in insulin-dependent diabetes mellitus. AB - Genetic factors contribute significantly to the development of diabetic nephropathy in patients with insulin-dependent diabetes mellitus. This report discusses some models of diabetic nephropathy that incorporate genetic susceptibility and presents strategies for identifying the responsible genes. To identify variation at a locus, newly developed methods are discussed that employ denaturing gradient gel electrophoresis to study sequence differences in both polymerase chain reaction-amplified DNA fragments and genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, no DNA sequence difference in that part of the angiotensinogen gene that codes for angiotensin I was found. However, with a probe corresponding to exons 7 and 8 of the insulin receptor gene and denaturing gradient gel electrophoresis of Rsal digestions of genomic DNA, different distributions of a DNA polymorphism were found in patients with fast as compared with slowly progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiologic data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected to permit the necessary genetic studies. PMID- 1457766 TI - Does antihypertensive treatment prevent progression of microalbuminuria to overt proteinuria in insulin-dependent diabetic patients? AB - Prospective studies in insulin-dependent diabetic patients have shown that microalbuminuria is a strong predictor of clinical nephropathy. Because this syndrome is associated with a dramatic excess in mortality, different types of intervention have been proposed for insulin-dependent diabetic patients with microalbuminuria to prevent or postpone clinical nephropathy. The effects of antihypertensive treatment are being extensively investigated. Beta-blockers, calcium antagonists, and angiotensin-converting enzyme inhibitors have proved effective in reducing albumin excretion and postponing overt proteinuria in hypertensive and normotensive insulin-dependent diabetic patients with microalbuminuria. However, many problems remain to be solved. A decrease in albumin excretion may not be an adequate endpoint for intervention trials, because it has been shown that patients with normal albumin excretion can develop diabetic nephropathy lesions, whereas patients with microalbuminuria alone may have little or no pathology. The patients included in these trials all had incipient diabetic nephropathy but exhibited different functional, and probably morphological, forms of the disease. For insulin-dependent diabetic patients with microalbuminuria, the real aim of antihypertensive treatment is not to reduce urinary albumin excretion or to prevent its progression but to preserve renal function and to reduce the incidence of premature cardiovascular deaths. To achieve this, we have to improve our knowledge of the natural history of the early pathology of diabetic nephropathy and of the mechanisms of action of antihypertensive treatment. New large-scale intervention trials will have to be designed in which the patients will have to be carefully characterized on the basis of functional and morphological data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457768 TI - [Cancer of the gastric stump]. AB - 627 cases of gastric cancer treated surgically during the last 5 years, at the Hospital Nacional "Edgardo Rebagliati Martins" from Instituto Peruano de Seguridad Social (Lima-Peru) were revised. 4 of the patients had been operated before of hemigastrectomy or antrectomy with pyloroplasty for peptic ulcer. The time between the first operation and diagnosis of cancer of the gastric stump was more than 20 years. 3 of these cases were able to be resected. The international incidence of cancer in the gastric stump is 1.1% to 9.2% according to different authors. The risk is higher after 15 years. In the pathogenesis are advocated the lower gastric acidity, biliary reflux, the presence of bacteria, the formation of nitrosamines, intestinal metaplasia, etc. Is necessary to perform periodic endoscopic survey in patients who were treated surgically of peptic ulcer with antrectomy or hemigastrectomy with more than 15 years of evolution. PMID- 1457767 TI - A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics. The Collaborative Study Group. AB - A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion > 500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) < 2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (< 140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a > 50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean +/- SD): male/female, 52%/48%; age, 35 +/- 8 yr; duration of diabetes, 21 +/- 7 yr; duration of proteinuria, 2.8 +/- 3.3 yr; duration of retinopathy, 4.5 +/- 4.1 yr; 50% of cohort presented with hypertension, duration, 4 +/- 4.7 yr; blood pressure, 139/86 +/- 19/12; SCr, 1.35 +/- 0.44 mg/dL; GFR 78 +/- 32 mL/min; BUN, 24 +/- 11 mg/dL; proteinuria, 3.1 +/- 3.3 g/day; cholesterol, 236 +/- 50 mg/dL; total glycosylated hemoglobin, 11.1 +/- 2.1%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457769 TI - [Polyps of the colon and the rectum]. AB - This is a retrospective study en 189 cases of colorectal polyps, from 1985-1989 including medical record review, pathologic diagnosis and surgical management. The main symptom was rectal bleeding. The follow up period and it's relation to colorectal cancer was evaluated, considering this entity as a premalignant lesion. 189 histopathology slides were reclassified according to the actual classification. Males were predominant (69%), with increasing incidence from the fifth decade (62% of the total); a 2% malignization rate was found. PMID- 1457770 TI - [New epidemic outbreak of cholera in Lima]. AB - We report a new outbreak of cholera on the beginning of last Summer (Dec. 91 and Jan 92). Were 281 patients, 63% male and 36% female, treated in our Cholera Unit of treatment; all of them coming from marginal-urban populations. There was a rate of lethality of inpatients of 0.46% and a mortality of 0.25% over the total of patients that we saw in our hospital; on this summer the outbreak is early and greatest than the summer of 1991. We can conclude that because of epidemic behavior during the whole 1991 and in the time elapsed of 1992, Peru has become an endemic zone of this new disease, while the current epidemiologic settings stay unchanged. PMID- 1457771 TI - [Redefining dyspepsia]. AB - On the last years there is a discussion about the dyspepsia for its prevalence and because the symptoms could indicate a serious disease. Now, there are problems with the terminology; functional or organic aspects; it is named non ulcer dyspepsia or ulcer-dyspepsia; also with the diagnosis and management. This paper is a review about the definition and etiology of dyspepsia. PMID- 1457772 TI - [Treatment of irritable bowel syndrome with a calcium antagonist (pinaverium bromide): experience with 40 cases]. PMID- 1457773 TI - [Early prognostic risk factors in acute pancreatitis: study of a representative population from Peru]. AB - Thirty-one patients with acute pancreatitis were prospectively evaluated using the Early Prognostic Risk Factors of Ranson and Bank & Wise, in order to assess severity of that condition. The purpose was to determine the usefulness of such factors as clues to orient diagnosis and treatment of acute pancreatitis, particularly in the most severe clinical forms; and the factibility of using them in our setting. The presence of 4 or more of Ranson's and/or 1 or more of Bank & Wise Factors fulfilling positive criteria, identified the patients with a high risk of complications and mortality. Hypocalcemia, leucocytosis and hyperuricemia were the most frequent findings in this group. The development of Early Objective Prognostic Risk Factors in acute pancreatitis, as a clinical concept, has improved the management of these patients. It allows to establish diagnosis and therapeutics upon objective basis. PMID- 1457774 TI - Small GTP-binding proteins as compartmental markers. AB - Each intracellular compartment involved in the biosynthetic/secretory pathway of eukaryotic cells bears at its surface at least one small GTP-binding protein. Most of them belong to a distinct branch of the p21ras superfamily, the Sec4/Ypt1/rab family. Other proteins are members of the ARF family. They play a key role in the regulation of budding and targeting/fusion events occurring during protein transport. PMID- 1457775 TI - Beauty and the yeast: compartmental organization of the secretory pathway. AB - Our perception of intracellular organelles and cellular architecture was initially based on striking light and electron micrographs of animal and plant cells. The high degree of compartmental organization within specialized mammalian secretory cells aided early efforts to track the movement of proteins through the organelles of the secretory pathway. In contrast, the morphological detail of the yeast Saccharomyces cerevisiae appeared superficially simple, even primitive, by comparison with the higher eukaryotic cells. However, the combination of genetic tools and the development of assays reconstituting vesicular traffic in yeast have facilitated the identification and characterization of individual proteins that function in the secretory pathway. Analogies between the function of yeast and mammalian proteins in vesicular traffic are being drawn with increasing frequency. In this review, the combination of genetic, biochemical, molecular and cell biological approaches used to study compartmental organization in the yeast secretory pathway will be discussed. The rapid progress in our understanding of yeast membrane traffic has revealed the beauty of working with this organism. PMID- 1457776 TI - Subcompartments of the endoplasmic reticulum. AB - The endoplasmic reticulum (ER) is the largest continuous endomembrane structure in the cytoplasm. It may be viewed as a series of unique subcompartments. In this review, we examine the rough ER, nuclear envelope and several smooth ER subcompartments. Consideration is given to the characteristic properties and functions of the ER and its domains, and to the formation and maintenance of subcompartments. Associations within the ER membrane bilayer, and with constituents of the cytoplasm and the ER lumen, contribute to the formation of domains and lead to the establishment of subcompartments that reflect specialized functions and vary according to the physiologic state and phenotype of the individual cell. Although the structural complexity of some ER subcompartments (such as the sarcoplasmic reticulum) is highly elaborate, the ER remains a dynamic organelle, subject to assembly and disassembly, capable of extensive remodelling and active in exchange with other organelles through mechanisms of membrane transport. PMID- 1457777 TI - Pathways of protein sorting and membrane traffic between the rough endoplasmic reticulum and the Golgi complex. AB - Recent results have provided increasing evidence for the existence of an intermediate membrane compartment between the rough endoplasmic reticulum and the Golgi complex which seems to function in protein sorting and the regulation of membrane traffic in the early part of the exocytic pathway. Localization of resident marker proteins has shown that this compartment consists of both peripheral and central elements. The aim of the present review is to combine the data on the pre-Golgi compartment with previous ideas of membrane traffic at the ER-Golgi interface. We propose a model which describes how mobile, endosome-like elements of the pre-Golgi compartment function in the generation of the compositional and functional boundary between the widely distributed ER and the more centrally located Golgi stacks. PMID- 1457778 TI - Biogenesis of secretory granules. AB - The biogenesis of secretory granules in endocrine, neuroendocrine, and exocrine cells is thought to involve a selective aggregation of the regulated secretory proteins into a dense-cored structure. The dense-core is then enveloped by membrane in the trans-Golgi network and buds, forming an immature secretory granule. The immature secretory granule then undergoes a maturation process which gives rise to the mature secretory granule. The recent data on the processes of aggregation, budding and maturation are summarized here. In addition, the current knowledge about the mature secretory granule is reviewed with emphasis on the biogenesis of the membrane of this organelle. PMID- 1457779 TI - Healthcare needs scale for patients with HIV/AIDS: content validation. AB - The authors of this study adapted Peters' (1987) community health specifications of patients' nursing requirements so they could be applied to patients with HIV/AIDS in hospital, dedicated outpatient HIV clinic, home care, and long-term care settings. The authors then collected validity evidence on the revised specifications, developed a sample of 62 multiple-choice items, and obtained content-related validity evidence via a judgmental review panel. The results produced: (a) a set of specifications for the environmental, psychosocial, physiological, and health behaviors domains; and (b) a 44-item scale of patient characteristics related to four levels of healthcare needs. PMID- 1457780 TI - The legacy of Kimberly Bergalis: unanswered questions. Counterpoint. PMID- 1457781 TI - The legacy of Kimberly Bergalis: unanswered questions. Point. PMID- 1457782 TI - Genital herpes and prevention of HIV infection: the report of a study in progress. AB - Although genital herpes is not a reportable disease, research has shown that about one in five women and one in eight men carry the antibody. The chronic ulcerative disease may place affected individuals at risk for human immunodeficiency virus (HIV) infection. This article directs attention to a study in-progress of adaptation in young adults with genital herpes. The use of qualitative and quantitative approaches in the study of adaptation will increase knowledge of adaptation regarding both process and outcome. PMID- 1457783 TI - Case management problems and home care. AB - The author summarizes a review of the case management problems encountered at the Visiting Nurse Service of New York, the largest certified provider of home care services to people with AIDS in the world. Case management problems can be divided into four general categories: client/significant others, housing/community, support services, and nurses' needs. Concrete solutions to these problems are discussed. As the number of people with AIDS increases, more home care agencies and discharge planners will need to consider these issues when planning care in the community. PMID- 1457784 TI - Educational learning needs of ANAC members--1991. AB - One of the purposes of the Education Committee of ANAC is to assess the learning needs of ANAC members. In order to achieve this purpose the Educational Needs Assessment tool was developed. It was included in the July 1991 issue of ANACDOTES and sent to the 1,116 members of ANAC. One hundred and fifty-five ANAC members responded (14%) by the cut-off date of August 15th. Demographic information about the respondents was compared to demographic data about ANAC members; the top three interest and expertise areas in the primary, secondary, tertiary prevention of HIV infection categories were identified. The Educational Needs Assessment tool can be used in other settings to plan programs and identify learning needs. PMID- 1457785 TI - Adolescents and HIV infection. PMID- 1457786 TI - Hidden messages. PMID- 1457787 TI - [Oral magnetic particles as an MR contrast medium for the gastrointestinal tract]. AB - The authors summarise their experience of four clinical studies with a negative oral contrast agent for magnetic resonance imaging of the abdomen and pelvis. 140 patients were enrolled in the studies. These were partly comparative studies pre- and post-contrast, partly at 0.5 and 1.5 T, partly pre-injection and post injection of glucagon. All patients received 800 ml of a suspension of oral magnetic particles "OMP". The distribution of this contrast agent was homogeneous throughout the entire GI tract. A complete or partial signal void was observed in all patients in T1, T2-, and intermediately weighted images. Generally, diagnostic information was higher after contrast. Artifacts caused by peristalsis and movement of the diaphragm were fewer after contrast. After contrast metallic artifacts were observed in a minority of patients. Adverse events after contrast were minimal; they included nausea and vomiting. PMID- 1457788 TI - [Manganese DPDP as a contrast medium for MR tomography of focal liver lesions. Tolerance and image quality in 20 patients]. AB - Twenty patients with focal liver lesions (18 metastases, 1 hepatocellular carcinoma, 1 cholangiocarcinoma) were given manganese DPDP as part of a multicentric phase II study of paramagnetic hepatobiliary MR contrast media. 5 mumol/kg manganese DPDP were injected into 10 patients in a concentration of 50 mumol/ml or 10 mumol/ml (3 ml/min). Blood pressure, pulse rate, ECG, respiratory rate, body temperature, blood and serum parameters and the patients' subjective feelings were recorded. MRI was performed with 1.5 T using T1- and T2-weighted sequences. 6 patients reported 8 side effects (flushing, feeling of warmth, metallic taste); 7 of these were produced by the 50 mumol concentration. Two hours after injection there was a significant reduction in alkaline phosphatase which was no longer present after 24 hours. On T1-weighted images manganese DPDP resulted in marked improvement in the contrast difference between the lesions and the liver parenchyma which resulted in a marked increase in the signal to noise ratio. Comparing the two concentrations, better results were obtained by the lower concentration. Extrahepatic uptake was found in the gallbladder, duodenum, pancreas, kidneys, gastric mucosa and myocardium. Manganese DPDP in a concentration of 10 mumol/ml and a dose of 5 mumol/kg is a well tolerated contrast medium which improves the demonstration of focal liver lesions in view of its distribution and uptake. The mechanisms for the transitory side effects require further studies. PMID- 1457789 TI - [The value of tumor volumetry as opposed to bidimensional determination of tumor size during follow-up of hepatic metastases from colorectal carcinoma]. AB - 36 patients with liver metastases due to colorectal carcinoma under treatment with arterial perfusion chemotherapy of the liver with 5-fluoro-2-desoxyuridine (FUDR) via a subcutaneous pump were investigated by axial liver CT at 6-monthly intervals. In all examinations a dynamic CT scan with intravenous bolus injection of contrast medium was carried out following a native scan. Changes in tumour size were documented by means of 1. volumetry and 2. bidimensional measurement according to WHO criteria. Since we were not able to assess small newly developing lesions within the liver using the volumetric classification, the WHO classification showed much higher sensitivity in cases of progressive disease. In addition, volumetric determination of tumour size by means of region-of-interest technique proved to be rather impracticable in clinical routine compared to bidimensional measurement. PMID- 1457790 TI - [The place of portangiography in the follow-up control of locoregional chemotherapy]. AB - 101 portangiographies in patients with liver metastases from colorectal primaries who underwent hepatic intraarterial or intraperitoneal chemotherapy were performed and studied between January 1991 and February 1992. 81% of the examinations did not involve complications. In 19% of the angiographies abnormalities of the arterial perfusion of the liver, like occlusion, dissection or narrowing of hepatic arteries, were found. We conclude that portangiography is a very important investigation before regional chemotherapy. PMID- 1457791 TI - [Magnetic resonance tomographic imaging of pulsatile CSF movement in communicating hydrocephalus before and after shunt placement]. AB - 16 patients with hydrocephalus communicans and 5 healthy volunteers were examined to demonstrate the pattern of the pulsatile CSF flow. After implantation of a CSF shunt system the same patients were examined again to show the influence of the shunt on the CSF pulsations. We used a flow-sensitised, cardiac-gated 2D FLASH sequence and analysed the phase and magnitude images. It could be shown that most patients (n = 12) had a hyperdynamic pulsatile flow preoperatively. After shunt implantation the pulsatile CSF motion and the clinical symptoms were improved in 8 of these patients. MRI of pulsatile CSF flow movement seems to be a helpful noninvasive tool to estimate the prognosis of a shunt implantation in patients with hydrocephalus communicans. PMID- 1457792 TI - [Sonographic findings in lateral ligament lesions of the upper ankle joint following conservative and operative therapy]. AB - 72 patients with injury of the ankle joint were examined with ultrasound after therapy. Sonographic findings were assessed by plain x-ray films and stress views. In 39 patients an injury of the lateral ligament was treated by surgery and in 33 patients without surgery. 40 patients showed a scar of the lateral ligaments. Patients treated without surgery and showing a scar in ultrasound demonstrated a smaller tilt of the talus in stress views than patients without scars. Measurement of stability was not possible. In conclusion, sonography is a valuable tool in examining the ankle joint after therapy. With regard to stability, stress films cannot be replaced by sonography. PMID- 1457793 TI - [Clinical potentialities and limitations of two- and three-dimensional time-of flight MR angiography in the diagnosis of carotid stenosis]. AB - For diagnosing a carotid artery stenosis, 26 patients underwent MR angiography. A spin echo (SE) sequence with presaturation on which the flowing blood appears with low signal intensity was applied, as well as a two- and three-dimensional gradient echo (GRE) sequence with flow compensation, showing blood flow with high signal intensity. Subsequently, projection angiograms were made from the MR images with a maximum intensity projection algorithm. Degree, length and localisation of a carotid artery stenosis were reviewed. To find out the clinical usability, the results of the MR angiograms were compared subsequently with the findings of intravenous digital subtraction angiography (i.v. DSA). In comparison with DSA a correlation in the degree of stenosis was noticed in 42 out of 48 SE-, in 39 out of 52 2-D GRE and in 41 out of 48 3-D GRE sequence angiograms. The length of 34 moderate and severe stenoses, demonstrated by DSA, was overestimated 5 times with the SE-sequence, 9 times with the 3-D and 23 times with the 2-D GRE sequence. MR angiography with a 3-D GRE sequence is suitable for screening for carotid artery stenosis. In cases of severe stenosis an SE sequence should be performed for more precise delineation of the stenotic lesion. PMID- 1457794 TI - [Doppler and duplex sonography of the vertebral arteries]. AB - In a prospective study 451 patients were examined with extracranial CW-Doppler sonography (mastoidal slope), suboccipital transcranial Doppler sonography and colour-coded duplex sonography to evaluate unusual vertebral arteries (hypoplasia, stenosis and occlusion). Colour duplex sonography was used as reference method. CW-Doppler sonography had a sensitivity of 100% and a specificity of 27% for the detection of an unusual vertebral artery. For transcranial Doppler sonography these values are 38% and 58%. Our study showed that CW-Doppler is a useful screening examination for identifying pathological findings of vertebral arteries. In case of abnormalities in CW-Doppler, duplex sonography, especially colour-coded duplex sonography, should be added. PMID- 1457795 TI - [Angiographic diagnosis in giant cell arteritis of the arm arteries]. AB - Three women of 66, 68 and 69 years of age presented with chronic arm claudication caused by giant cell arteritic stenoses and occlusions of their arm arteries. In the early stage of the disease, arteriography revealed smooth or undulatory long segment narrowings. Subsequently, spindle-shaped filiform stenoses developed. They were unilateral in one patient, bilateral-symmetric in another and like a string of beads in the third. In the end, untreated arteritis resulted in smoothly tapered occlusions of the diseased vessels. In patients with symptoms and signs suggestive of giant cell arteritis, typical arteriographic findings may confirm the diagnosis even if histopathological proof is lacking. PMID- 1457796 TI - [Magnetic resonance angiography of the renal veins and the vena cava inferior for the staging of renal cell carcinoma]. AB - The staging of renal cell carcinoma (RCC) comprises exclusion of tumour expansion into the renal veins and the inferior vena cava (IVC). In 44 patients with RCC these vessels were examined using MRA on the basis of "time-of-flight" technique (coronal/axial 2D GE-flash-sequence, MIP-algorithm). The method was evaluated against contrast-enhanced CT and DSA in normal conditions and tumour-involved IVC (n = 12) and renal veins (n = 32) respectively. Following analysis of projection angiograms (PA) and individual slices the results of MRA without contrast material included an information on vascular tumour extension that was identically safe as CT and DSA. In coronal slice orientation tumour extension into the vena cava was proven in 100%, and into the renal veins in 84%. Additional axial slices were necessary to demonstrate tumour extension into the renal veins in unclear cases. Single slices showed to be superior to PA for a correct identification of the size of the tumour thrombus. PMID- 1457797 TI - [Stent-supported percutaneous therapy of iliac vein stenosis following operative thrombectomy and placement of a shunt]. AB - Among 15 patients with acute thrombotic disease of pelvic veins who had been submitted to operative thrombectomy and creation of arteriovenous fistula in the groin, 12 presented with stenotic lesions 3 months later. These stenoses were submitted to percutaneous angioplasty. If angioplasty failed, percutaneous placement of a vascular stent (wall stent) was performed immediately (n = 7). Stenting in cross-over-technique proved practicable in all cases. Secondary stenotic disease in the exclusively dilated area was observed in 3/5 cases and was also treated with a wall stent. In one patient with recurrent stenoses who refused stenting, extended thrombosis occurred after occlusion of the AV-fistula. At mid-term PTA was successful in only two cases. Intimal hyperplasia was observed in only one wall stent treated patient. Percutaneous treatment of iliacal stenoses in patients with postthrombotic syndrome may be performed safely under the protective effect of the fistula. With the presented technique, patency of pelvic veins could be restored in 11/12 patients with postoperative significant venous stenoses. PMID- 1457798 TI - [Radiation dosage during hysterosalpingography using a digital image intensifying technique]. AB - Hysterosalpingography using a digital and conventional image intensification technique was carried out on two groups of 32 patients as part of investigation for infertility. Radiation dose was recorded as surface dose. In 51.7% of digital images and 54.8% of conventional images the findings were normal. Surface dose with conventional technique was 442 +/- 144 cGy/cm2, significantly higher than 207 +/- 113 cGy/cm2 with digital image intensification. The number of exposures was also significantly higher when using the conventional technique. The digital images showed no lack of diagnostic detail when compared with the conventional 100 mm films. PMID- 1457799 TI - [Arterial interventional measures using carbon dioxide (CO2) as a contrast medium]. PMID- 1457800 TI - [A rare case of bilateral benign kidney tumors with a complication]. PMID- 1457801 TI - [Symptomatic chylous prepatellar bursitis following lymphography]. PMID- 1457802 TI - [The intramural esophageal hematoma]. PMID- 1457803 TI - [Osteopoikilosis]. PMID- 1457804 TI - Hemolymph concentrations of host ecdysteroids are strongly suppressed in precocious prepupae of Trichoplusia ni parasitized and pseudoparasitized by Chelonus near curvimaculatus. AB - Regulation of ecdysteroid production in lepidopteran prepupae was studied using a parasitic wasp (C. near curvimaculatus) which specifically suppresses host prepupal ecdysteroid production after the induction of precocious host metamorphosis. At the developmental stage at which the hemolymph of the unparasitized metamorphosing host has its maximum titer of prepupal ecdysteroids, the hemolymph of 4th instar "truly parasitized" hosts (hosts with a surviving endoparasite) had a strongly reduced ecdysteroid titer. However, during the photophase about 12 h later, just prior to emergence of the parasite larva, an ecdysteroid peak was observed in the host hemolymph. Fourth instar pseudoparasitized prepupal hosts (in which the endoparasite was not present or died early in development) exhibited a sustained suppression in the hemolymph ecdysteroid titer. Small 5th instar pseudoparasitized hosts, which normally would molt to a 6th instar prior to metamorphosis, but which precociously attained the prepupal stage, also had a strongly reduced ecdysteroid titer. The late increase observed in truly parasitized hosts could be completely prevented by surgical removal of the parasite 24 h earlier, resulting in a titer similar to that in pseudoparasitized hosts. HPLC analysis of ecdysteroids in normal, truly parasitized, and 4th or 5th instar pseudoparasitized prepupae showed that both ecdysone and 20-OH ecdysone* were suppressed in truly and pseudoparasitized prepupae, with ecdysteroid levels being lowest in pseudoparasitized hosts. These data, and those of Brown and Reed-Larsen (Biol Contr 1, 136 [1992]), showing endoparasite secretion of ecdysteroids just prior to its emergence from the host, strongly indicate that: (1) the prepupal peak in truly parasitized hosts originates from the endoparasite, and (2) the low level of ecdysteroids in pseudoparasitized hosts results from the host's intrinsic inability to express a normal level of prepupal ecdysteroid titer. While precocious 4th or 5th instar prepupae of similar size had similarly suppressed ecdysteroid titers, smaller 4th instar prepupae had a lower ecdysteroid titer than larger, precocious 5th instar prepupae. Rare 5th instar pseudoparasitized prepupae that were of nearly normal size showed a prepupal ecdysteroid titer distinctly greater than those of the usual smaller, precocious 5th instar prepupae. The data suggest that the competence of the host to express a normal hemolymph titer of prepupal ecdysteroids is more closely correlated with the size of the prepupae than with the instar attained. PMID- 1457805 TI - A protein from Daudi cell line conditioned medium induces ovarian dysgenesis in Drosophila melanogaster. AB - From a medium in which Daudi cells had been grown, we isolated by HPLC a protein that caused ovarian abnormalities in adult females of Drosophila melanogaster when injected into preblastoderm embryos. This protein, whose apparent M(r) is between 30,000 and 50,000, was found to be a moderately polar compound which is heat stable and whose activity is destroyed by acidification. The protein is characteristic of medium conditioned from Daudi cells. PMID- 1457806 TI - Non-random distribution and co-localization of purine/pyrimidine-encoded information and transcriptional regulatory domains. AB - In order to detect sequence-based information predictive for the location of eukaryotic transcriptional regulatory domains, the frequencies and distributions of the 36 possible purine/pyrimidine reverse complement hexamer pairs was determined for test sets of real and random sequences. The distribution of one of the hexamer pairs (RRYYRR/YYRRYY, referred to as M1) was further examined in a larger set of sequences (> 32 genes, 230 kb). Predominant clusters of M1 and the locations of eukaryotic transcriptional regulatory domains were found to be associated and non-randomly distributed along the DNA consistent with a periodicity of approximately 1.2 kb. In the context of higher ordered chromatin this would align promoters, enhancers and the predominant clusters of M1 longitudinally along one face of a 30 nm fiber. Using only information about the distribution of the M1 motif, 50-70% of a sequence could be eliminated as being unlikely to contain transcriptional regulatory domains with an 87% recovery of the regulatory domains present. PMID- 1457807 TI - A simple protocol for the automation of DNA cycle sequencing reactions and polymerase chain reactions. AB - Automated DNA sequencing methods using robotic workstations have been previously reported, however it is often an arduous task to import these technologies into a laboratory. We describe protocols making use of a Beckman Biomek 1000 robotic workstation to prepare polymerase chain reactions (PCRs) and "cycle sequencing" reactions to be performed in a Perkin Elmer Cetus System 9600 thermocycler. The combination of these two instruments allows a high throughput of PCR and DNA sequencing reactions. The programs described are freely available via anonymous file transfer protocol (FTP). PMID- 1457808 TI - Comparison of the genomic organizations of the rat grp78 and hsc73 gene and their evolutionary implications. AB - GRP78, a 78-kDa protein localized in the endoplasmic reticulum, is a member of the HSP70 protein family. However, unlike hsp70 which is intronless and belongs to a multigene family, grp78 is a single copy gene and contains intervening sequences. In this aspect, the grp78 gene resembles more closely that of the constitutively expressed heat shock cognate gene, hsc73. In this report, we compare the grp78 and hsc73 genes and show that: (1) the intron/exon junctions of the two genes are not conserved, but occur at similar positions; (2) while the protein sequences are highly conserved, being 62% identical, the conservation is concentrated at discrete regions over the N-terminal three-fourths of the protein; (3) this conservation represents the ATP binding and structural domains shared among the members of the HSP70 family; (4) the C-terminus is highly divergent and likely represents domains specific for the individual family members; and (5) sequences partially homologous to the grp78 5' UTR and signal sequence, which targets GRP78 into the ER, are found within an additional first intron of hsc73. The evolutionary implications of these two genes are discussed. PMID- 1457809 TI - Gene sequences of chicken BDNF and NT-3. AB - The respective amino acid sequences of mature brain-derived neurotrophic factor (BDNF) and of mature neurotrophin-3 (NT-3) are identical among mammals, making these among the structurally conserved factors known. Here we show that only a single conservative amino acid substitution distinguishes the chicken mature NT-3 protein from its mammalian counterpart. Chicken mature BDNF shows slightly more variation, differing from mammalian BDNF at several positions. We also note the presence of amino acid sequence motifs in the precursor protein sequences of chicken BDNF and NT-3 that are universally conserved among all known mammalian neurotrophin precursors and have been demonstrated to play a crucial role in promoting correct processing of the pro-proteins. PMID- 1457810 TI - New protocols for DNA sequencing with dye terminators. AB - We have developed a new two-step protocol for Taq cycle sequencing using the ABI dye terminators. First, linear PCR is used to extend a single sequencing primer in the absence of dye terminators. This nested set of polynucleotides as well as the original primer then serve as starting points for the cycled termination reactions. Using this method it is easily possible to generate dye terminator raw data with much improved signal intensity beyond 400 to 500 bp. We also present a quick and convenient method to remove excess of dye terminators by gel filtration using 24 mini columns fixed in a block of perspex. PMID- 1457811 TI - A standard file format for data from DNA sequencing instruments. AB - There are now a number of machines for determining DNA sequences. These devices are currently of two types: those such as the Applied Biosystems 373A and the Pharmacia A.L.F. which interpret the sequences of samples as they run on gels within the machine, and those, such as the Bio-Rad and Amersham readers that scan and analyse conventional autoradiographs. Both types of machine can produce their data in the form of traces which represent the band intensity of each of the four base types at each position in the sequence. At present all the machines write files in different formats. We describe a machine independent format for storing data derived from automatic sequencing machines. Files in this format can store the derived sequence, the traces and a set of confidence measures for each base. We have adopted the format as the standard for our sequence handling software. PMID- 1457812 TI - The isolation and sequence of sheep interleukin 4. AB - A cDNA corresponding to sheep IL-4 has been isolated and sequenced. The cDNA was synthesized using PCR and oligonucleotides designed from conserved regions of IL 4 cDNA published sequences. The nucleotide and amino acid sequences of a sheep IL 4 cDNA are presented and compared with sequences from other species. At the nucleic acid level, the sheep cDNA shared 73 and 62% homology with human and mouse cDNA homologues, respectively, while comparisons at the amino acid level revealed 50% homology with human IL-4 and 33% with the mouse homologue. Total amino acid homology between these species was 27%. PMID- 1457813 TI - Nucleotide sequence of the bovine interleukin-6 gene promoter. AB - We report the cloning and sequencing of a 1252 base pairs (bp) DNA fragment containing the bovine interleukin-6 (IL-6) gene promoter. This fragment was isolated from a bovine genomic library constructed in the lambda GEM11 vector. Comparison with human, murine and rat IL-6 gene promoters reveals a high degree of conservation of the 200 bp immediately upstream of the RNA CAP site. This region contains nucleotide stretches matching with consensus sequences recognized by transcription factors, including NF-KB, CREB and NF-IL6. A potential AP-1 binding site is found 284 nucleotides upstream of the RNA CAP site. The bovine IL 6 gene promoter cloned upstream of the bacterial chloramphenicol acetyl transferase (CAT) gene was shown to be active in bovine and ovine cells. PMID- 1457814 TI - Nucleotide sequence and exon-intron structure of the bovine transition protein 1 gene. AB - The nucleotide sequence and exon-intron structure of the bovine transition protein 1 gene was determined. It consists of 2 exons (E1, 139 bp; E2, 29 bp) and a single intron (220 bp). The position of the transcription initiation site was determined 30 nucleotides upstream of ATG. TAAATA- and CAAT-boxes were found 60 and 121 bp upstream of the ATG-translation start point, respectively. It was observed that transition protein 1 is highly conserved in mammals at the nucleotide as well as at the amino acid level. PMID- 1457815 TI - The sea urchin erg homolog defines a highly conserved erg-specific domain. AB - A genomic clone, isolated from a phage library prepared from the DNA of the sea urchin Lytechinus variegatus, was shown by sequence analysis to be a homolog of the ets family genes, ERG and Fli-1. It contains an open reading frame of which the coding region begins at a consensus 3' splice site and extends for 173 amino acid residues. The first 84 amino acids are homologous with all members of the ets gene family, while the remainder of the sequence is only homologous with the human ERG and murine Fli-1 genes. This latter region, designated R, represents a highly conserved erg-specific domain. PMID- 1457816 TI - M13 single-strand purification using a biotinylated probe and streptavidin coated magnetic beads. AB - A new method for M13 single-strand purification has been developed and tested. The procedure gives sufficient DNA for one set of thermally cycled sequencing reactions when analysed on the Applied Biosystems 373A fluorescent DNA sequencer. For this report, 250 random M13 subclones with 1-2 Kb inserts were grown and prepared using this method. PMID- 1457817 TI - Sequence and pattern of expression of a bovine homologue of a human mitochondrial transport protein associated with Grave's disease. AB - A human cDNA has been isolated previously from a thyroid library with the aid of serum from a patient with Grave's disease. It encodes a protein belonging to the mitochondrial metabolite carrier family, referred to as the Grave's disease carrier protein (GDC). Using primers based on this sequence, overlapping cDNAs encoding the bovine homologue of the GDC have been isolated from total bovine heart poly(A)+ cDNA. The bovine protein is 18 amino acids shorter than the published human sequence, but if a frame shift requiring the removal of one nucleotide is introduced into the human cDNA sequence, the human and bovine proteins become identical in their C-terminal regions, and 308 out of 330 amino acids are conserved over their entire sequences. The bovine cDNA has been used to investigate the expression of the GDC in various bovine tissues. In the tissues that were examined, the GDC is most strongly expressed in the thyroid, but substantial amounts of its mRNA were also detected in liver, lung and kidney, and lesser amounts in heart and skeletal muscle. PMID- 1457818 TI - Sequences of the human and bovine genes for the mitochondrial 2-oxoglutarate carrier. AB - The oxoglutarate carrier transports 2-oxoglutarate across the inner membranes of mitochondria in an electroneutral exchange for malate or other dicarboxylic acids. The sequences of its human and bovine genes have been determined from overlapping genomic clones generated by polymerase chain reactions by use of primers and probes based on the bovine cDNA sequence. The bovine and human genes are split into 6 and 8 exons, respectively, and five introns are found in the same positions in both genes. The coding and protein sequences are 93% and 96.6% identical, respectively. The human oxoglutarate carrier protein is 314 amino acids in length and, in common with the bovine protein, does not appear to have a processed presequence to help to target it into mitochondria. PMID- 1457819 TI - Indexing the sequence libraries: software providing a common indexing system for all the standard sequence libraries. AB - We describe a set of programs for creating and using indexes for the distributed forms of the major sequence libraries. The indexes conform to the specification of those distributed on cd-rom by the EMBL sequence library. The programs create entry name, accession number, author and freetext indexes and a brief directory index. If a suitable application program is given an entry name or accession number these indexes allow rapid retrieval of sequences or annotation. Similarly the author and freetext indexes provide the data for extremely fast searching on author names and "keywords". The indexing programs can create indexes for EMBL, Swiss-Prot, GenBANK, PIR and NRL3d libraries. We also describe the organisation and use of the different sequence libraries and their index files. PMID- 1457820 TI - Significance of the positivity of some ELISA tests different as concerning the antigenic source in interpreting the western blot indeterminate sera in monitoring the epidemiology of high risk populations. AB - The paper analyses 50 pairs of sera pre-elevated within the "sentinel" epidemiological surveillance in a population exposed to a high risk at a 2 months interval. At the first determination all these sera showed an indeterminate Western Blot pattern; after 2 months, 93.7% revealed the occurrence of a certainly positive pattern. The paper is an analysis of the way in which different ELISA kits diagnosed at the first determination the Western Blot indeterminate sera. The purpose of the paper is to adopt a methodology of accurately diagnosing HIV infections in a population exposed to a high risk within an epidemiological surveillance of the "sentinel" type where the receiving of a second serum sample is quite difficult. PMID- 1457821 TI - Presence of IgE class antibodies with cardiolipinic and treponemal specificity in syphilis. Quantitative evaluation by IgE prist radio-immuno-assay. AB - 60 serum samples (reactive in VDRL, ELISA-Reiter, FTA-Abs tests) from 25-45 years old male patients with untreated latent syphilis (EL) (30 cases) and persistent positive treated syphilis (ET+) (30 cases) were tested for IgE by IgE-PRIST. On 30 sera from 25-45 years old male healthy persons, normal mean value for serum IgE was established: 159.63 +/- 124.09 U/ml. Cardiolipin and group treponemal IgE fractions were indirectly calculated by the difference between the specific activity induced by sera as such and that induced by sera absorbed with cardiolipin and group treponemal sorbents. In EL, total IgE level was 197 +/- 107 U/ml; cardiolipin IgE -24.9 +/- 8.3 U/ml and group treponemal IgE 35.8 +/- 6.6 U/ml. In ET, total IgE value was 152.6 +/- 122.5 U/ml, cardiolipin IgE -11 +/- 10.5 and group treponemal IgE -26.6 +/- 14.2 U/ml. Summing up the two specificities, the total specific IgE represent about 1/3 from total IgE in EL and 1/5 in ET+. Taking into account the short half-life (2-3 days) of IgE presence of a significant proportion of specific IgE in those two stages proves, by their continuous synthesis paralleling antigenic stimulation, the presence in various tissular zones of viable treponemas as sources of antigens. PMID- 1457822 TI - Development of an irradiated vaccine that protects against enterotoxigenic Escherichia coli diarrhoea. AB - In the pathogenesis of diarrhoea in man bacteria adhesion to enterocytes is mediated by specific CFA/I or CFA/II antigens. A perorally administered vaccine was prepared from E. coli H10407 (078:H11) by irradiation with electrons with high energy (EHE). Two hours after cimetidine administration rats were immunized per os with 5 irradiated vaccine doses at 4-day intervals. Seven days after the last immunization animals were infected by inoculating 1 x 10(9) germs in the ligated intestinal loop. Reduction of the intestinal secretion by over 50% 18 hours after inoculation was considered an efficient protection marker. The obtained results have proved a significant reduction of the intestinal secretion in immunized animals infected with serotypes 078:H11(63 +/- 4%) and 078:H12(59 +/ 5%) as compared to non-immunized animals. Experimental induction of the intestinal protection against Escherichia coli enterotoxigenic (ETEC) strains points to the possibility of using this type of irradiated vaccine in the prophylaxis of diarrhoea in man. PMID- 1457823 TI - Experimental study on intradermal antitetanus antityphoid immunization. AB - A new type of concentrated unadsorbed Tetanus vaccine was administered in animals by intradermal route, associated or not with Typhoid vaccine. The results of the laboratory tests demonstrated that this vaccine is innocuous and produces minimal reactions. A single doses of Tetanus vaccine inoculated in guinea pig or rabbit resulted in a relevant titer which increased when the Typhoid vaccine was associated. Also, in such immunized guinea pigs, a remarkable resistance to tetanic toxin was achieved. The levels of the active or passive typhoid protective power as well as that of the agglutinating antibodies were not influenced by the association of the Tetanus vaccine to the Typhoid vaccine. Therefore, when the Typhoid vaccine suspended in Tetanus vaccine was administered intradermally to the animals by Jet injector, it had not a negative effect for none of the two components, had a beneficial effect upon the levels of determined antibody production and allowed an easier and more rapid administration of these vaccines. PMID- 1457824 TI - The anti-initiator action of p-methoxyphenol phosphate upon the transformation of normal human embryo cells induced by benzo(a)pyrene. AB - The association of p-methoxyphenol phosphate (10(-5)M) to benzo(a)pyrene treatment (10(-6)M) reduced significantly the anchorage independent growth and the number of transformed foci of the human embryo lung fibroblasts, after six passages from treatment application. Results from cytogenetic analysis show that p-methoxyphenol phosphate induced the decrease of numerical and structural chromosome aberration after the first passage of the treated cells. In terms of the results obtained by cytogenetic analysis the reduction of genetic instability seems to remain constant from the first to the sixth passage in the cell cultures treated with p-methoxyphenol phosphate associated to benzo(a)pyrene. PMID- 1457825 TI - Oncogenes and their mechanisms of action. PMID- 1457826 TI - Science education reform: broadening the agenda. PMID- 1457828 TI - Anti-sense transforming growth factor alpha oligonucleotides inhibit autocrine stimulated proliferation of a colon carcinoma cell line. AB - Many carcinoma cells secrete transforming growth factor alpha (TGF alpha). A 23 base anti-sense oligonucleotide that recognizes the TGF alpha mRNA inhibits both DNA synthesis and the proliferation of the colon carcinoma cell line LIM 1215. The effects of the anti-sense TGF alpha oligonucleotide are reversed by epidermal growth factor (EGF) at 20 ng/ml. When the LIM 1215 cells are grown under serum free conditions, the anti-sense TGF alpha oligonucleotides have their greatest effects at high cell density (2 x 10(5) cells/cm2), indicating that the secreted TGF alpha is acting as an exogenous growth stimulus. In addition, at higher cell densities, the kinase activity of the EGF receptor is activated and the receptor is down-modulated. The cell density dependent activation of the EGF receptor is inhibited by the application of the antisense TGF alpha oligonucleotides. PMID- 1457827 TI - Molecular basis of loss-of-function mutations in the glp-1 gene of Caenorhabditis elegans. AB - The glp-1 gene encodes a membrane protein required for inductive cell interactions during development of the nematode Caenorhabditis elegans. Here we report the molecular characterization of 15 loss-of-function (lf) mutations of glp-1. Two nonsense mutations appear to eliminate glp-1 activity; both truncate the glp-1 protein in its extracellular domain and have a strong loss-of-function phenotype. Twelve missense mutations and one in-frame deletion map to sites within the repeated motifs of the glp-1 protein (10 epidermal growth factor [EGF] like and 3 LNG repeats extracellularly and 6 cdc10/SWI6, or ankyrin, repeats intracellularly). We find that all three types of repeated motifs are critical to glp-1 function, and two individual EGF-like repeats may have distinct functions. Intriguingly, all four missense mutations in one phenotypic class map to the N terminal EGF-like repeats and all six missense mutations in a second phenotypic class reside in the intracellular cdc10/SWI6 repeats. These two clusters of mutations may identify functional domains within the glp-1 protein. PMID- 1457829 TI - Genetic dissection of the signaling domain of a mammalian steroid receptor in yeast. AB - The mechanism of signal transduction by steroid receptor proteins is complex and not yet understood. We describe here a facile genetic strategy for dissection of the rat glucocorticoid receptor "signaling domain," a region of the protein that binds and transduces the hormonal signal. We found that the characteristics of signal transduction by the receptor expressed in yeast were similar to those of endogenous receptors in mammalian cells. Interestingly, the rank order of particular ligands differed between species with respect to receptor binding and biological efficacy. This suggests that factors in addition to the receptor alone must determine or influence ligand efficacy in vivo. To obtain a collection of receptors with distinct defects in signal transduction, we screened in yeast an extensive series of random point mutations introduced in that region in vitro. Three phenotypic classes were obtained: one group failed to bind hormone, a second displayed altered ligand specificity, and a third bound hormone but lacked regulatory activity. Our results demonstrate that analysis of glucocorticoid receptor action in yeast provides a general approach for analyzing the mechanism of signaling by the nuclear receptor family and may facilitate identification of non-receptor factors that participate in this process. PMID- 1457830 TI - The nuclear-mitotic apparatus protein is important in the establishment and maintenance of the bipolar mitotic spindle apparatus. AB - The formation and maintenance of the bipolar mitotic spindle apparatus require a complex and balanced interplay of several mechanisms, including the stabilization and separation of polar microtubules and the action of various microtubule motors. Nonmicrotubule elements are also present throughout the spindle apparatus and have been proposed to provide a structural support for the spindle. The Nuclear-Mitotic Apparatus protein (NuMA) is an abundant 240 kD protein that is present in the nucleus of interphase cells and concentrates in the polar regions of the spindle apparatus during mitosis. Sequence analysis indicates that NuMA possesses an unusually long alpha-helical central region characteristic of many filament forming proteins. In this report we demonstrate that microinjection of anti-NuMA antibodies into interphase and prophase cells results in a failure to form a mitotic spindle apparatus. Furthermore, injection of metaphase cells results in the collapse of the spindle apparatus into a monopolar microtubule array. These results identify for the first time a nontubulin component important for both the establishment and stabilization of the mitotic spindle apparatus in multicellular organisms. We suggest that nonmicrotubule structural components may be important for these processes. PMID- 1457831 TI - Biochemical and physiological changes induced by anthrax lethal toxin in J774 macrophage-like cells. AB - Experiments were performed to probe the mechanism by which Bacillus anthracis Lethal Toxin (LeTx) causes lysis of J774 macrophage-like cells. After incubation of cells with saturating concentrations of the toxin, two categories of effects were found, which were distinguishable on the basis of chronology, Ca(2+) dependence, and sensitivity to osmolarity. The earliest events (category I), beginning 45 min postchallenge, were an increase in permeability to 22Na and 86Rb and a rapid conversion of ATP to ADP and AMP. Later events (category II) included alterations in membrane permeability to 45Ca, 51Cr, 36Cl, 35SO4, 3H-amino acids, and 3H-uridine, beginning at 60 min; inhibition of macromolecular synthesis, leakage of cellular lactate dehydrogenase and onset of gross morphological changes, at approximately 75 min; and cell lysis, beginning at 90 min. Category II events exhibited an absolute requirement for extracellular Ca2+ and were blocked by addition of 0.3 M sucrose to the medium, whereas category I events were attenuated, but not blocked, by either of these conditions. On the other hand, both ATP depletion and the category II events were blocked in osmotically stabilized medium that was also isoionic for Na+ and K+. This suggests that permeabilization of the plasma membrane to monovalent cations and water may be the earliest of the physiological changes described here. The resulting influx of Na+ and efflux of K+ would be expected to cause depletion of ATP, via increased activity of the Na+/K+ pump. Subsequently the influx of Ca2+, induced by depletion of ATP, imbalances in monovalent cautions, and/or more dramatic changes in permeability due to influx of water, would be expected to trigger widespread changes leading ultimately to cytolysis. PMID- 1457832 TI - Artificial organs of the future. PMID- 1457833 TI - Cross-sectional assessment of weekly urea and creatinine clearances in patients on continuous ambulatory peritoneal dialysis. AB - In 55 patients on continuous ambulatory peritoneal dialysis, the authors determined daily renal and dialysate clearances of urea nitrogen (CUN) and creatinine (CCr). Results are expressed as weekly CUN in liters (Kt) divided by liters of total body water determined from a nomogram (V). The authors calculated weekly CCr as the weekly dialysis clearance plus the average of renal CUN and CCr (to correct for creatinine secretion); they normalized total weekly CCr to 1.73 m2 body surface area. Mean weekly Kt/V and CCr were 2.1 and 65.2, respectively. Mean dietary protein intake by dietary survey was 0.85 g/kg body weight. Protein catabolic rate (PCR) calculated from urea kinetics was 0.94 g/kg standardized weight (V/0.58); PCR was significantly (p < 0.01) correlated with Kt/V (r = 0.53). The authors used linear regression to determine PCR, as follows: PCR = 0.80 [weekly Kt/V]/3 + 0.39. This slope is nearly 1.5 times that reported for the relationship of PCR to [weekly Kt/V]/3 in hemodialysis patients. Eighty-two percent of patients on continuous ambulatory peritoneal dialysis had more than the targeted minimum weekly Kt/V of 1.7, 71% had a weekly CCr more than the targeted minimum of 50, and 75% had a PCR > 0.8 g/kg/day. In support of the hypothesis that Kt/V requirements are related to peak concentration control rather than to time averaged blood urea nitrogen, patients on continuous ambulatory peritoneal dialysis have a higher PCR at given Kt/V values compared to hemodialysis patients. These patients are more likely to have a PCR > 0.8 if weekly Kt/V > 1.7. PMID- 1457834 TI - Initial clinical experience with centrifugal pumps coated with the Carmeda process. AB - From September 5 to November 4, 1991, four consecutive patients placed on centrifugal ventricular assist devices (VADs) for cardiac failure were supported with Biomedicus pumps coated with the Carmeda bioactive surface. The study included three men and one woman aged 52-65 years. Two patients were supported with a right VAD, one with a left VAD, and one with a biventricular VAD. Support ranged from 35.5 to 65.75 hr, and VAD flows ranged from 1.0-5.5 L/min. Three patients were weaned from the VADs, and two survived. At explant, all four systems had clots adherent to the surface of the tubing and connectors on the pump outflow side of the circuit. Two patients had clots in the pump. Some of the clots were firmly adherent, whereas others dislodged easily after being rinsed with saline. All patients received heparin for insertion, and in three patients, heparin was reversed with protamine. Two patients received no further anticoagulation, and two received continuous heparin within 24 hr of implant to maintain activated clotting times of 140-150 sec. All patients had bleeding complications before and after VAD placement, necessitating multiple blood product transfusions. One patient who was weaned and survived had multiple thromboembolic strokes. These data suggest that clots can form on surfaces coated with the Carmeda process, even if a low dosage of heparin is used. PMID- 1457835 TI - Intraoperative timing may provide criteria for use of post-cardiotomy ventricular assist devices. AB - When surgeons consider ventricular assist devices (VADs) for post-cardiotomy support, unnecessary delays and early use can have detrimental effects on patient outcome. The authors analyzed the timing of intraoperative events in all patients receiving post-cardiotomy VAD support at their institution during a 2-1/2 year period (N = 17). They used ability to wean patients from VAD support as a measure of outcome. Neither preoperative risk factors nor the timing of distinct intraoperative events (e.g., cross-clamp time, total bypass time, delay to VAD) significantly differed between those patients able (Group I, n = 9) and those unable (Group II, n = 8) to be weaned from VAD support. The authors did find, however, that the time intervals from completion of the cardiac procedure to insertion of either an intra-aortic balloon pump (time to IABP) or VAD (time to VAD) were predictive of outcome when normalized to the duration of the cardiac procedure (DCP). [Time to IABP]/DCP ratios of < 1.0 versus > 1.0 (p = 0.02) and [time to VAD]/DCP ratios of < 2.5 versus > 2.5 (p = 0.10) each segregated Group I and II patients, respectively. Appropriate timing criteria for VAD insertion may be predicted during surgery by consideration of the duration of the cardiac procedure. This approach may attenuate tendencies to delay VAD use without leading to premature VAD insertion in the post-cardiotomy setting. PMID- 1457836 TI - The importance of patient mobility with ventricular assist device support. AB - Patients bridged to transplantation with ventricular assist devices (VADs) often require prolonged support. To reduce complications associated with bed rest, the authors developed a program to mobilize patients with VADs. Between August 1986 and May 1992, 25 men and 7 women aged 12-65 years (mean: 42.4 years) were bridged for possible transplantation. The 32 patients were supported with either a Novacor (n = 9) or a Thoratec (n = 23) VAD. Thirty-one patients were turned within 2-12 hr of VAD insertion and received range of motion therapy. Twenty-six patients sat in a chair 2-16 days (mean: 5 days) after VAD insertion. Twenty-one patients used a stationary bicycle, and 23 patients were ambulatory 3-57 days (mean: 11 days) after VAD insertion. Two patients were transplanted within 72 hr of device insertion. Twenty-one of the 23 ambulatory patients were successfully transplanted or weaned from the VAD and discharged from the hospital. Two ambulatory patients who were difficult to rehabilitate (ambulatory 22 and 57 days, respectively, after VAD insertion) died before transplantation. In conclusion, VAD patients should be mobilized early because the VAD can improve exercise capability and survival rate. PMID- 1457837 TI - Photoinduced prevention of tissue adhesion. AB - Postoperative tissue adhesion causes retarded wound healing and the need for reoperation; it can even be life threatening. In this report, the authors present prototype materials and performance of newly developed tissue adhesion prevention technology based on photocurable polysaccharides. Polysaccharides used were hyaluronic acid and chondroitin sulfate, both of which were partially derived with photoreactive groups such as cinnamoyl, coumarin, and thymine. Photoreactive hyaluronic acids with low degrees of derivatization were soluble in water. Films of cinnamated hyaluronic acid or an aqueous solution of cinnamated chondroitin sulfate were photocured by ultraviolet irradiation, resulting in water adsorbable films or water swollen gels, respectively. Gelation was due to intermolecular dimerization between cinnamoyl groups. The authors provide two potentially applicable examples: 1) a photocured, water swollen hydrogel film, and 2) a photocurable chondroitin sulfate buffer solution. The authors used hydrogel films to cover the peritoneum after mechanically injuring its surface. Histologic examination showed neither tissue nor cell adhesion, and only a minimal inflammatory response. When tissues were coated with a photocurable chondroitin sulfate solution, the viscous solution was converted to a hydrogel upon ultraviolet irradiation, resulting in in situ tissue covering. Although an optimal molecular design has not yet been found, unique features of mucopolysaccharides (e.g., high water uptake; biodegradability and bioresorbability; and nontoxicity of photodimerizable groups) may result in the development of photoinduced tissue adhesion prevention technology. PMID- 1457838 TI - A method to reduce thrombogenicity of a graft for small diameter arterial substitution seeded with autologous venous tissue fragments. AB - The authors successfully applied a method to accelerate endothelialization by tissue fragmentation to a small diameter fabric vascular prosthesis. Tissue fragment seeded grafts showed rapid healing of the neointima. The thrombogenicity of the collagen fibrils in the fragments, however, caused major problems when the method was applied to small diameter grafts: the positively charged collagen fibrils aggregated the negatively charged platelets. The authors masked the fibrils electrostatically with heparin molecules, which are negatively charged. A canine jugular vein was resected, minced into tissue fragments, and suspended in the heparin solution; it then was sieved through the wall of a fabric prosthesis. The grafts (4 mm internal diameter and 3.5 cm in length) were implanted into both carotid arteries of six dogs (12 grafts). Tissue fragment seeded grafts without heparin also were implanted into six dogs. As a control, preclotted fabric grafts were implanted into six dogs (12 grafts). These grafts occluded within 1 week, whereas all the masked grafts were patent without thrombi. In vitro examination of heparin release revealed that approximately 92% of heparin in the graft was released during the first 5 hr, but approximately 6% remained after 25 hr. These results indicate that the method is applicable to small diameter arterial grafts. PMID- 1457839 TI - In-storage hypothermic perfusion for heart and lung transplantation. AB - The authors developed a new waterproof-packed infusion device for easy and sterile in-storage hypothermic perfusion during organ transportation for heart and lung transplantation. They examined the accessibility and efficacy of this infusion device for portable heart and lung preservation in canine transplant models. Sixteen heart and bilateral lung blocks were preserved by an in-storage hypothermic perfusion technique using the infusion device with University of Wisconsin solution. Of 16 dog recipients, 5 underwent orthotopic heart transplantation with cardiopulmonary bypass, and 5 dogs received left lung transplantation; the remaining heart and lung blocks were intrathoracically transplanted into 6 dogs. Functional status and histology of 11 heart and 11 lung allografts were evaluated by post-transplant course, hemodynamic parameters, arterial blood gas measurements, microscopic examination, and so on. Eleven transplanted hearts showed good cardiac performance and maintained systemic circulation after weaning from cardiopulmonary bypass. Eleven transplanted lungs had excellent respiratory function, and all five dogs with left lung transplantation survived for 5-46 days (mean: 18.8 days). These results suggest that in-storage hypothermic perfusion with this waterproof-packed infusion device can be a useful technique for long-term organ preservation in heart and lung transplantation. PMID- 1457840 TI - A bioartificial ventricle used as a totally implantable circulatory assist device. AB - The authors designed a totally implantable circulatory assist device consisting of a bioartificial ventricle composed of a skeletal muscle ventricle lined with a bioartificial endocardium. The bioartificial endocardium consists of a structural matrix made of a polyurethane porous membrane, fragmented blood vessels, and collagen gel. The authors prepared the polyurethane porous membrane by solvent cocasting with salt powder. They used collagen gel with fragmented goat carotid vein to perform in vitro construction of the bioartificial endocardium. For in vivo construction of the bioartificial endocardium, the authors used a modified version of the tissue fragment method for vascular prostheses. The authors prepared suspensions of tissue fragments using collagen gel with fragmented goat carotid artery. They used a highly porous fabric vascular prosthesis as a structural matrix; tissue fragments were entrapped on the outer surface of the prosthesis, and the prosthesis then was implanted into the carotid artery of four adult goats. In specimens 1 and 3 months postimplantation, cells from the fragmented tissue regenerated an endothelium-like monolayer sheet on the inner surface of the prostheses. Output of a prototype bioartificial ventricle reached 660 ml/min at an afterload of 60 mmHg and a preload of 20 mmHg. Based on these data, the authors conclude that the bioartificial ventricle is promising as an implantable device with excellent antithrombogenicity. PMID- 1457841 TI - Novel instrumentation monitoring in situ platelet adhesivity with a quartz crystal microbalance. AB - The quartz crystal microbalance (QCM) in a solution is capable of sensing an extremely small mass change in the nanogram range. In this article, the authors attempted to apply QCM to in situ continuous monitoring of platelet adhesion in plasma. The instrumentation consisted of a piezoelectric quartz crystal vacuum deposited with gold and connected to two electrodes, an oscillation circuit, a frequency counter, and a DC source (5 V), coupled with a personal computer, a television monitor, and a printer. The authors noted resonant frequency shifts to determine weight increase upon cell adhesion. A QCM sensor, with the sensitivity of 1 ng/Hz, was placed horizontally in platelet poor plasma. The authors did not observe any measurable frequency shift upon adding a suspension of non-adherent cells, such as red blood cells and prostaglandin I2-sensitized platelets, indicating that QCM does not count the increase in the mass of cells that simply settled on the quartz. They did observe, however, a time-dependent frequency shift upon addition of platelet rich plasma. Coupled with visual determination of numbers of adherent platelets and their morphology under scanning electron microscopy, they found that the magnitude of shift and its time dependence seem to correlate not only numbers of adherent platelets, but to their spreading state, indicating that QCM detects only the weight at the focal contact region of adherent cells. This suggested that the former contributes to the early phase of the frequency shift, and the latter contributes to a shift change after a longer period of incubation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457842 TI - Prevention and control of bacterial infections associated with medical devices. AB - Bacteria that grow in association with medical devices always form slime enclosed biofilms, within which they are protected, to a large extent, from the bactericidal activity of chemical biocides and antibiotics. Mature biofilms (> 7 days) are demonstrably resistant to 500-5,000 times the concentrations of these agents than are necessary to kill free floating (planktonic) cells of the same organism. The authors have discovered that this well established inherent resistance of biofilm bacteria to antibacterial agents can be completely obviated if these agents are applied to these adherent populations within an electric field. The killing of biofilm bacteria by antibiotics can be dramatically enhanced by relatively weak electric fields (1.5 V/cm and 15 microA/cm2) that, in themselves, have no deleterious effects on these slime protected populations adherent to plastic or metal surfaces. This bioelectric technology can readily be used to enhance the preimplantation sterilization of medical devices by biocides. The authors suggest that it may also be used to control biofilm formation and consequent infection by electrically enhanced perioperative antibiotic prophylaxis and by electrically enhanced penetration of antibiotics to kill the biofilm bacteria that form the inherently resistant nidus of chronic device related infections. PMID- 1457843 TI - Influence of Kt/V and protein catabolic rate on hemodialysis morbidity. A long term study. AB - Urea clearance over time, divided by volume of total body water (Kt/V) and protein catabolic rate (PCR), were calculated monthly in 88 long-term hemodialysis patients. Patients were divided into four groups: Group A (n = 40), Kt/V > 1.0 and PCR > 1.0 g/kg/day; Group B (n = 7), Kt/V > 1.0 and PCR < 1.0; Group C (n = 24), Kt/V < 1.0 and PCR > 1.0; and Group D (n = 17), Kt/V < 1.0 and PCR < 1.0. Various clinical, biochemical, and morbidity factors were compared. Group A had significantly less morbidity than did the other groups (p < 0.05). Blood urea nitrogen, serum creatinine, serum albumin, and phosphorus were lower in Group B than in the other groups (p < 0.05). These data suggest that determination of Kt/V and PCR is important for predicting dialysis morbidity and that they should be monitored together for adequacy of therapy and dialysis quality assurance. PMID- 1457844 TI - Continuous measurement of blood volume during hemodialysis by an optical method. AB - A new method is described to noninvasively and continuously measure changes in blood volume (BV) during hemodialysis by means of an optical reflection method with an optical monitor (950 nm) clipped onto the arterial blood line. The amount of reflected light (L) appeared to be linearly proportional to the erythrocyte concentration (r = 0.91). Changes in L correlated well with changes in erythrocyte concentration during hemodialysis (r = 0.94). A study in 10 patients on regular dialysis was done. The BV decrease after 3 hr of treatment was 17.0 +/ 5.2%, and it correlated with the amount of fluid withdrawn by ultrafiltration (mean, 2,519 +/- 589 ml). Five hypotensive episodes were seen that were characterized by a higher rate of BV fall during the preceding 15 min (9.9 +/- 1.9 versus 3.6 +/- 4.3%/hrp; p < 0.05) and by a lower BV value at that moment (78.2 +/- 3.4 versus 84.5 +/- 4.5%; p < 0.025) than in the other five patients at comparable times. It was concluded that this optical method was a means to detect hypovolemia at an early stage and to prevent ultrafiltration induced hypotension. PMID- 1457845 TI - Total body water measured by bioelectrical impedance in patients after hemodialysis. Comparison with urea kinetics. AB - Bioelectrical impedance (BEI) measurements have been used to measure total body water volume (VBEI). The VBEI were measured after hemodialysis in 14 patients, as was dialyzer blood water urea clearance (KBW) and dialysate urea clearance (KD). Urea clearance based on the mass transfer coefficient, KoA, was determined (KKoA). Residual renal function was measured, and three point variable volume single pool urea kinetic modeling (UKM) was done. Urea distribution volumes were calculated using the measured urea clearance values from blood water (VBW), dialysate (VD), and KoA (VKoA) as inputs. Direct dialysate quantitation was calculated based on total dialysate collections to measure urea clearance (KDDQ) and urea distribution volume (VDDQ). Total body water estimates were made using the Hume and Watson anthropometric formulas (VHUME and VWATSON). It was found that average VBEI (34.76 L) was larger than VBW (27.50 L) and VD (26.69 L), but it was not different from VKoA (32.15 L), VHUME (35.15 L), or VWATSON (34.53 L). Linear regression revealed a good correlation between VBEI and both VBW and VD (R = 0.873 and 0.882, respectively). The BEI measurements provide a simple method for measuring total body water in dialysis patients that correlated well with UKM volumes. PMID- 1457846 TI - Non-invasive determination of recirculation in the patient on dialysis. AB - Recirculation of blood flow occurs when the fistula flow rate is inadequate to support the desired dialyzer blood flow. The percentage recirculation is normally calculated using the blood urea nitrogen of blood samples from the two dialyzer blood lines and a peripheral blood sample. However, this method is time consuming, costly, and may not always give accurate measurements. A technique was developed to measure recirculation using the injection of saline into the venous dialysis line. For this technique, an optical detector is placed across the arterial dialysis tubing, and the light intensity, which is proportional to the hematocrit, is continually measured using a computerized data collection system. After a baseline data collection period, 10 ml of saline is injected into the venous dialysis line using the sampling port. The saline that appears in the arterial dialysis line as a result of recirculation will cause a dilution of the blood and an increase in light intensity. In vitro testing showed an excellent correlation between the area under the dilution curve and percentage recirculation. This technique will provide a quick, inexpensive, and reliable measurement of recirculation. PMID- 1457847 TI - Cardiopulmonary recirculation in dialysis. An underrecognized phenomenon. AB - Access recirculation can be determined by measuring blood temperature or blood water concentration in the dialyzer inlet after injecting a bolus of cold saline into the venous line. In patients with access recirculation, some of the cooled venous blood re-enters the blood inlet line soon after injection, resulting in a sharp transient drop in its temperature. There is also a prompt increase in blood water concentration at the dialyzer blood inlet caused by the dilution effect of the recirculated saline. In this study, data are reported on four patients studied under conditions where no access recirculation could occur because blood was returned to a second access or into a central vein. In these patients, transient cooling of the blood in the dialyzer inlet and a transient hemodilution after venous line injection of cold saline was still observed. These observations can be explained by passage of the injected saline through the heart and pulmonary blood vessels and return of a portion of the cooled blood to the vascular access, bypassing the systemic capillary microcirculation. This "cardiopulmonary recirculation" can cause dilution of urea in dialyzer inlet blood, with resulting errors in urea kinetic modeling and in computing access recirculation. PMID- 1457848 TI - Microporous small diameter PVDF-TrFE vascular grafts fabricated by a spray phase inversion technique. AB - Microporous prostheses of 1.5 mm internal diameter were fabricated with a polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE)n co-polymer by the spray phase inversion technique. Some of the grafts were made piezoelectric by poling under a high electrical field. Overall, 24 poled grafts (P) and 24 unpoled grafts (UP) (15-22 mm in length) were implanted in the infrarenal aorta of 48 adult rats. Patency rates in P were 100% (8/8) at 2 days, 100% (8/8) at 2 weeks, 75% (6/8) at 6 months, and 92% total (22 of 24). Patency rates in UP were 100% (8/8) at 2 days, 63% (5/8) at 2 weeks, 100% (8/8) at 6 months, and 88% total (21 of 24). Thus there was no significant difference in patency between the two types of grafts. Both showed similar macroscopic and microscopic findings. At 2 days, fibrin deposition was somewhat heavier on the poled grafts, but no difference in surface platelet deposition could be detected. Endothelialization was observed from both anastomoses at 2 weeks and was almost complete at 6 months. The excellent biocompatibility of PVDF-TrFE and the microporous structure of the grafts were probably the dominant factors in success with these grafts. Although piezoelectric activity in excised cleaned poled prostheses remained significantly higher than that in the control UP, the charges developed may have been too small to exert a biologic effect, either because of insufficient dipole orientation or inadequate mechanical deformation. PMID- 1457849 TI - A new, all silicone rubber small vessel prosthesis. AB - A new small vessel prosthesis composed entirely of silicone rubber was developed. The new prosthesis has a trilaminar wall structure consisting of: 1) a porous blood contacting layer designed to promote the deposition of a pseudoneointima (PNI) from blood flowing over the surface; 2) a solid middle layer the thickness of which is adjusted to provide approximately the same radial compliance as the host artery; and 3) a porous outer layer that promotes connective tissue attachment to the exterior of the prosthesis to limit tissue capsule formation around the implant and preserve its compliance after healing of the perigraft tissues. The new graft also has excellent suture retention in addition to its other desirable physical characteristics. The mechanical integrity of the textured surfaces was first evaluated in vitro with cyclic flexure testing at a 20-30% strain. Grafts of 4 mm inside diameter by 5 cm length were then implanted in the left carotid artery of adult dogs for an 8 week period. Seven animals were studied. Platelet inhibitors were administered postoperatively. The patency rate was 86% (six of seven); all grafts except the first remained widely patent. After the animals were killed, the grafts were surgically exposed, and compliance was measured directly. The PNI from the grafts was then studied with light and scanning electron microscopy, and morphometric measurements were made of PNI thickness over the length of the graft. Overall, the grafts retained 80% of their preimplant compliance (n = 5); however, in the absence of any postoperative complications such as hematoma or infection, the grafts remained essentially isocompliant with the host artery during the duration of this study. PMID- 1457850 TI - In vitro performance of venous valve prostheses. An experimental model study. AB - The performance of fresh and glutaraldehyde fixed bovine jugular vein valves (10 mm diameter) was investigated in an experimental flow loop that provides adjustable flow rates and a downstream oscillatory pressure. Three different venous valve (VV) conduit geometries (curved [C], straight [S], and tapered [T]), were tested. The flow loop consisted of two independently adjustable components, with the mean flow generated by adjusting the elevation difference between the head tank and outflow chamber. An adjustable sinusoidal pressure pulse was superimposed on the downstream of a VV to mimic the respiratory effects. Flow visualizations were made using 100 microns mica chip tracers in the laser illuminated flow fields. To assess VV performance under various flow conditions, the closure opening (CO), partial opening (PO), and leaflet fluttering (LF) were evaluated. At a given pulse pressure, the three conduits required different flow rates to reach CO mode. At 12 cm H2O pulse pressure, the fresh valve in C-conduit exhibited stable CO operation at a flow rate of 1.01 ml/sec. That in S and T conduits required 1.67 ml/sec and 2.25 ml/sec, respectively. At higher flow rates, PO and LF performances were observed in all three conduits. Different threshold values of pulse pressure were needed to reestablish the CO operation mode for the C, S, and T conduits, individually. These observations provide some insight into the role of conduit geometry and sinus configuration in the function of VV. PMID- 1457851 TI - Optimal management of a ventricular assist system. Contribution of flow visualization studies. AB - The Novacor (Baxter Novacor, Oakland, CA) Left Ventricular Assist System (LVAS) incorporates a versatile microprocessor based controller that permits a variety of operating modes. These include internally triggered automatic synchronous counterpulsation, electrocardiogram triggered synchronous operation, and full to empty or fixed rate asynchronous operation. The aim of this pilot study was to determine the extent to which washing of the blood contacting surfaces of the pump may be optimized by suitable choice of operating mode. Visualization of flow fields adjacent to surfaces in confined areas requires small, neutrally buoyant tracer particles for feature extraction. A novel technique using fluorescent tracer particles (100 microns), an argon laser, and a low pass optical filter has been developed for this purpose. Particle motion was tracked from video images and calculations were made of velocity. Flow visualization was performed under conditions that simulated clinically observed hemodynamic conditions, typical of the immediate post-implant period. At a given LVAS output, fluid speed in the vicinity of the inflow valve tended to increase at higher LVAS beat rates (and consequently lower LVAS stroke volumes). This and future work may well be useful in selecting the optimum modes of LVAS operation as a function of the hemodynamic status of the patient. PMID- 1457852 TI - Effect of stationary guiding vanes on improvement of the washout behind the rotor in centrifugal blood pumps. AB - In centrifugal pumps, there always exists an area of stagnation between the rear of the rotor and the rear housing wall that promotes thrombus formation around the axle. Some current devices overcome the problem by using holes in the rotor plane, leading to increased hydrodynamic losses and shear stress. In this study, a simple apparatus was developed to overcome this problem. Guiding vanes were fixed to the rear housing wall. These vanes decrease the tangential velocity of the fluid and thus the centrifugal force, leading to an increased secondary flow toward the axle. The effect of such vanes was studied in videographic and ultrasound studies. An increase of washout and mixing between the flow layers could be demonstrated (stay time < 200 msec versus several seconds without vanes). In the first animal experiment using nonoptimized vanes, there was no thrombus at the back plane or the seal, and only a small thrombus at the transition between axle and rotor. Hemolysis was slightly elevated (3.2 mg/dl versus 2.5 mg/dl in control experiments). In conclusion, it is highly likely that this simple system will improve the flow characteristics in centrifugal pumps. PMID- 1457853 TI - Fluid mechanics of left ventricular assist system outflow housings. AB - Using the Novacor (Baxter Novacor, Oakland, CA) Left Ventricular Assist System (LVAS) as a test bed, phasic flow patterns were analyzed for three outflow valve housing designs: 1) a triple sinus; 2) an axisymmetric concentric sinus (CS); and 3) a modified triple sinus (MS). The 21 mm Carpentier-Edwards trileaflet pericardial heart valve prosthesis was used for all experiments done on the three housing designs. The LVAS was actuated by a laboratory model of the Novacor LVAS control console, and it was connected to a mock flow loop with an adjustable afterload system to provide physiologic pressures and flows (Pao, 120/80 mmHg; pump output [PO], 2-6 L/min). Laser illuminated flow visualization techniques were used to investigate the phasic flow patterns of the housings, and the visualization derived velocity was verified by laser Doppler velocimetry at several selected points in the field. Formation of vortices behind the leaflets during the LVAS ejection phase was observed in each of the housing designs. They were well organized, and they circulated with the greatest strength in MS. These vortices tended to lie in a plane parallel to the main flow axis, with the rotational velocity increasing with the stroke volume of the LVAS. In the CS and the MS housings, a circumferential flow that provided good washing of this region was observed behind the stents. PMID- 1457854 TI - Quantitation of right ventricular shape changes after left ventricular assist device implantation. AB - Complex effects of left (LV) and right ventricular (RV) interaction account for changes in RV function during LV assist device (LVAD) support. It has been hypothesized that changes in RV cross-sectional shape (RVS) may be a contributing factor in the development of RV dysfunction during LVAD support. To test the hypothesis that the RVS would become more circular as a result of septal shift during LVAD support, 13 patients were studied before and after LVAD implantation. The shape of the RV was quantified using a shape factor (SF) that was equal to (4 x pi x area)/P2, where P is the perimeter of RVS. The RV area and perimeter were measured from digitized images of the RV obtained by transesophageal echocardiography in patients before and after LVAD implantation. The group SF increased considerably after LVAD (SFpre = 0.78 +/- 0.12 versus SFpost = 0.88 +/- 0.07, p < 0.05). Patients were divided into three groups: 1) patients whose RV exhibited a low SF pre-LVAD that increased significantly, 2) those with a moderate SF pre-LVAD that increased slightly, and 3) those who had high pre-LVAD SF (< 0.90) that did not change. The decompression of the LV caused by LVAD implantation results in a shift of the septum from right to left, increasing SF. This increase is more pronounced in some patients. Quantitation of the degree of RV SF change may help predict the development of RV failure during LVAD support. PMID- 1457855 TI - A motor integrated regenerative pump as the actuator of an electrohydraulic totally implantable artificial heart. AB - The authors have developed a new actuator to drive an electrohydraulic totally implantable artificial heart. The basic concept of this artificial heart is that the blood pumps are implanted in the thorax and an actuator is placed separately in the abdominal region. The actuator is a regenerative pump that pumps fluids against high pressures and is thin enough for easy implantation. The rotor-magnet of the brushless DC motor is mounted on the impeller of the pump to miniaturize the actuator and reduce the number of moving parts. The height, diameter, and weight of the actuator are 32.5 mm, 73 mm, and 360 g, respectively. A pair of oil ports is connected to the left and right blood pumps with mesh reinforced tubes filled with silicone oil. The blood pumps are alternately driven by bidirectional rotation of the motor. Performance of the system was evaluated in in vitro and in vivo experiments. Maximum output of the right heart was 6.7 L/min in both experiments. Systemic circulation was well maintained in acute animal experiments using 49 and 50 kg goats. The feasibility of the actuator was confirmed. PMID- 1457857 TI - Two-dimensional cell manipulation technology. An artificial neural circuit based on surface microphotoprocessing. AB - The precise regional control of cell adhesion and growth on a substrate may create two-dimensional tissue formation, as in a neural network. To prepare a neural circuit, micropositioning of neural cells and guidance of extending axons in a given region are required. In general, the adhesion of neural cells and their axonal extension are mediated by adhesive proteins found in the extracellular matrix. This paper describes a novel surface photoprocessing that enables the creation and guidance of regionally selective cell adhesion, leading to a neural network. The non-adherent region was created by chemical fixation of a photoreactive hydrophilic co-polymer of azidostyrene and N, N dimethylacrylamide on a hydrophobic substrate. Ultraviolet irradiation with the use of a photomask placed on a substrate hydrophilically modified the irradiated regions, which was evident in ESCA and contact angle measurements. The addition of a collagen buffer solution resulted in collagen adsorption only on the non irradiated hydrophobic portions. Seeded neuroblastoma cells adhered only on collagen-adsorbed pathways 130 microns in width. One day after seeding, nerve growth factor was added to the culture medium, resulting in cell differentiation from growth to axonal extension. The axons grew along the collagen-adsorbed pathways. Sooner or later, cells were interconnected with extended axons, which was clearly visible microscopically. Further culturing completed the honeycomb like patterning, as designed. The surface processing developed here can manipulate fundamental cellular behavior, leading to two-dimensional patterned tissue, which may provide information on the morphogenesis of the neural network and neurotransmission. PMID- 1457856 TI - Fabrication of a jellyfish valve for use in an artificial heart. AB - For a valve to be fabricated seamlessly into an artificial heart (AH) blood pump, a jellyfish valve has been developed, in which a thin membrane is fixed at the center of a valve seat having several spokes to protect against prolapse of the membrane. The valve is superior in performances to a Bjork-Shiley valve, and reveals good blood compatibility. The valve would be very useful not only for AH animal study, but for future clinical use in infants to adults. Several institutions are already trying the valve. In this paper, the fabrication of the jellyfish valve is introduced, and in vitro and in vivo results summarized. A computer aided design (CAD) system was developed to cut a male wax mold of the valve seat. The input parameters to the CAD are diameter, height, thickness of rim, number of spokes, width and thickness of spokes, etc. Jellyfish valves with diameters of 4 to 27 mm have already been fabricated for many types of AHs and assist pumps. PMID- 1457858 TI - Selective feedback control of spastic musculature in a canine model. AB - Muscular spasm, the etiology of which remains elusive, has been difficult to control. The authors, therefore, proposed selective restraint of forced contractions by a closed-loop circuit. In four dogs, the strap (n = 6) and thyroarytenoid (n = 4) muscles were submitted to tetanic contractions via bipolar supramaximal stimulation (30 Hz, 6 mA, 0.5 msec) of ansa hypoglossi and recurrent laryngeal nerves, respectively. Subsequent reduction of distance between two sonomicrometer crystals embedded into muscle was used in lieu of "spastic information" for a stimulator to deliver blocking signals through tripolar electrodes passed downstream. By modifying frequency (30-110 Hz) and current (60 95%) distribution between the central cathode and the peripheral anodes, significant relaxation (up to 100%) was recorded within "blocking windows," varying with each nerve (3-18 mA sweeps). The selective restraint of unwanted contractions, leaving "normal" subthreshold tone undisturbed, may offer a more mature approach to spastic disorders than destructive procedures, such as nerve section and its chemical counterpart, botulinum toxin injection. PMID- 1457859 TI - A pathway for information transmission to the inner ear. Application to cochlear implants. AB - The use of cochlear implants as an aid to neurosensory deafness is becoming an established procedure. The transmission of a processed speech signal is accomplished either transcutaneously via radiofrequency or percutaneously by connector coupling. Whereas the former is sensitive to electromagnetic interference, the latter increases the risk of infection. To overcome these disadvantages, an infrared (IR) system for transmission through the tympanic membrane was devised and tested. The transmitter/receiver consisted of an IR light emitting diode (LED; 920 nm) and a photovoltaic cell. The LED was placed inside the auditory canal of four dogs and the photovoltaic cell in the tympanic cavity over the cochlear promontory. A sinusoidal signal modulation was applied to the LED. The emitted signal was detected undistorted after crossing the tympanic membrane, with an average absorbance of 20%. High frequency cut-off was adequate for cochlear implant purposes and audio prosthetic devices in general. The authors conclude that the tympanic membrane may be used as a translucent sealed interface to transmit data in the audio range to the middle and inner ears, with small power loss, good frequency response, and immunity to interference. PMID- 1457860 TI - Implantation of a cardioverter-defibrillator after coronary artery bypass surgery. AB - The implantable cardioverter-defibrillator (ICD) has been used in conjunction with surgical coronary revascularization for prevention of postoperative malignant arrhythmias. However, there is no consensus regarding which patient should receive concomitant insertion of the ICD system in a one stage (patches and generator) or two stage (patches, and subsequent implantation of the generator) procedure. To assess differences in hospital course and outcome, the authors studied 8 survivors of sudden death syndrome and 17 patients with preoperative ventricular tachycardia refractory to conventional antiarrhythmic therapy who underwent coronary revascularization and prophylactic implantation of an ICD system in either one or two stages. Patients with advanced coronary disease, poor ventricular function, and silent ischemia received the ICD system in one stage. Those with good ventricular function and well defined coronary pathology received only patches concomitant with myocardial revascularization. Seventy-nine percent of the patients with patches needed subsequent implantation of the ICD generator, as determined by postoperative electrophysiologic studies. There were three postoperative deaths unrelated to arrhythmias. There was no difference between the groups regarding the number of ICD discharges. It was concluded that the prophylactic use of the ICD system is an important adjuvant in the treatment of postoperative malignant arrhythmias for patients undergoing myocardial revascularization. The insertion of the ICD, however, should be based on pathophysiologic considerations and postoperative electrophysiologic findings. This may result in important savings in terms of unnecessary cost and operative procedures. PMID- 1457861 TI - Prophylactic implantable defibrillator patches in patients at high risk for malignant ventricular dysrhythmias. AB - The indications for prophylactically placing implantable cardioverter defibrillator (ICD) patches at cardiac surgery are unclear. Over the past 4 years, 25 patients have undergone placement of prophylactic ICD patches at the authors' institution. Indications were severe coronary artery disease with ventricular tachycardia (VT) (n = 14) or ventricular fibrillation (VF) (n = 2), and left ventricular aneurysmectomy and/or subendocardial resection (SER) (n = 9). Four patients died in-hospital, three from refractory VT (which could be transthoracically cardioverted until recurrence was unremitting), and one from congestive heart failure (CHF). All of the remaining 21 patients underwent post operative electrophysiologic studies (EPS), and 12 had inducible VT (8/14 CABG, 4/7 SER). Eight of the 12 inducible patients had generators implanted, whereas 3 patients were controlled medically. One patient refused generator implantation and died at home from sudden cardiac death, and one initially non-inducible patient required late ICD generator placement, yielding a total of nine patients who received generators. All nine of these patients are currently alive at 14 +/- 7 months follow-up, and five have subsequently received appropriate ICD discharges. In patients undergoing cardiac surgery considered preoperatively or intraoperatively to be at increased risk for VT/VF and too unstable for preoperative EPS, prophylactic ICD patches should be considered. PMID- 1457862 TI - A new RV-PA conduit with a natural valve made of bovine jugular vein. AB - A new RV-PA conduit with a natural valve was developed using bovine jugular vein. To maintain the natural, mechanical properties of the veins, a hydrophilic cross linking reagent, a glycerol polyglycidyl ether polyepoxy compound (PC) was used. The treatment has already been proven in the field of vascular grafts to be able to reduce antigenicity, biodegradability, and degenerative changes such as calcification, to induce antithrombogenicity with hydrogenicity, and to improve affinity to host cells. Bovine jugular veins were cross-linked with the reagent and were implanted as a conduit into the RV-PA position in six dogs. The main PA was ligated after implantation. One animal died due to bleeding 2 days after implantation; the other animals were healthy and allowed to survive until they were sacrificed. The graft was very soft and as pliable as native tissue, and was as strong as a heart valve. Post-operative catheterization and angiography showed adequate function of the valve. Macroscopic and microscopic observations revealed the antithrombogenicity of the graft in this animal study. These results indicated that this newly developed biologic valved conduit has a high probability of overcoming many problems observed in existing RV-PA conduits. PMID- 1457863 TI - The effect of prolonged left ventricular support on myocardial histopathology in patients with end-stage cardiomyopathy. AB - To determine the histopathologic effect of prolonged (> 30 days) left ventricular unloading on the myocardium, the authors studied myocardial tissue specimens from eight men (mean age, 40.8 years) with end-stage cardiomyopathy (six idiopathic, two ischemic) who were supported with the HeartMate (Thermo Cardiosystems, Inc., Woburn, MA) left ventricular assist device (LVAD) as a bridge to cardiac transplantation. The average length of support was 79.6 days (range, 31-136 days). Before left ventricular support was instituted, transthoracic echocardiography revealed that all patients had significantly dilated left ventricular cavities (average left ventricular diastolic dimension, 7.2 cm). Tissue specimens from the core of the left ventricular apex, which is removed at the time of LVAD implantation, were compared through pathologic examination with specimens from the explanted hearts at the time of cardiac transplantation. Apical core specimens from all patients exhibited extensive areas of attenuated myocardial fibers, combined with wavy patterns in some areas. In these regions, the nuclei of the cardiac myocytes from idiopathic cardiomyopathy specimens were neither pyknotic nor disappearing, as was noted in an infarcted area of a specimen from one patient with ischemic cardiomyopathy. At the time of heart transplantation, myocardial tissue specimens from the explanted hearts had a significant decrease or disappearance of stretched fibers. There was also a slight increase in interstitial replacement fibrosis, as well as an increase in the diameter of the myocardial fibers. These findings appear to correlate with the clinical impression of improved native ventricular function and with radiographic findings and decreased chamber size during prolonged ventricular support. PMID- 1457864 TI - Preparation of an RGD ALB conjugate. In vitro analysis of cellular responses. AB - RGD (Arg-Gly-Asp) tripeptide was identified as the minimal active core peptide sequence common to adhesive proteins. In this paper, the authors report preparation of RGD containing peptide albumin conjugate (RGD ALB), and its effects on cellular adhesive function in vitro. RGD ALB was prepared via a coupling reaction of albumin with pentapeptide (GRGDS; Gly-RGD-Ser) by water soluble carbodiimide. Bovine endothelial cells (ECs) adhered to and spread well on a surface coated with RGD ALB, whereas few ECs adhered on surfaces coated with GRGESP-albumin conjugate (GRGESP peptide with little cell attachment activity; false control) and albumin. Cellular behavior, such as adhesion, spreading, growth, and migration, on surfaces coated with GRD-ALB, fibronectin (FN), and vitronectin (VN) were quantitatively examined. Adherent cell number on RGD ALB coated surfaces was larger than on those coated with FN and VN. Cell morphology on RGD ALB coated surfaces was similar to that on FN coated surfaces. The cell growth and migration activities on RGD ALB coated surfaces were almost equal to those coated with FN and VN. Thus, RGD ALB was found to promote cell adhesion, migration, and growth as effectively as fibronectin. This indicates that an artificial adhesive protein, simply derived with bioactive peptidyl ligand, can find versatile applications in fields in which cellular events play a critical role--for example, extracellular matrices and wound healing promotion aids. PMID- 1457865 TI - Patients on hemodialysis rely on nephrologists and dialysis units for maintenance health care. AB - The extent to which hemodialysis patients rely on nephrologists for primary medical care is unknown. The authors surveyed 74 in-center hemodialysis patients to obtain demographic data and information about primary medical care and subspecialty referrals and follow-up. Health care maintenance was also assessed. All patients were dialyzed in a free-standing university affiliated dialysis unit. The mean age of the patients was 55 +/- 17 years; most were women (43/74) and on hemodialysis more than 3 years (48/74). Most of the patients did not have a family physician and relied on the nephrologist for health maintenance care (80%) and the treatment of minor acute illnesses (91%). The most common non-renal chronic illnesses were gastrointestinal disease (32%), heart disease (26%), and diabetes (26%). Although referrals to subspecialists occurred in 55% of patients during the preceding year, nephrologists usually provided ongoing management care (gastrointestinal disease 21/24, heart disease 10/19, diabetes 12/19). Over half the women had a Papanicolaou's test within 3 years and 72% had a routine mammogram that, in most cases, had been ordered by the nurse practitioner or nephrologist. Because nephrologists provide primary medical care to the majority of dialysis patients, preventive health care protocols, such as mammography and cancer screening, should be incorporated into the nephrology practice in chronic dialysis units. PMID- 1457866 TI - Inadequate dialysis increases gross mortality rate. AB - The authors correlated the dialysis parameters of 613 patients on hemodialysis with their morbidity and mortality. Dialysis prescription (Kt/V) was calculated according to the dialyzer, blood flow, and dialysis time. Dialysis delivered was calculated using percentage urea reduction (PUR). Eighty patients who underwent dialysis in three units had only predialysis blood urea nitrogen (BUN) values available. Mean predialysis BUN was between 58 +/- 16 and 83 +/- 17 mg/dl. Patients with predialysis BUN > 100 mg/dl ranged from 0-22%, and those with predialysis BUN < 50 mg/dl ranged from 0-41%. Kt/V prescribed was between 0.45 and 1.75. Mean dialysis time was 191 +/- 28 min, and blood flow was 327 +/- 48 ml/min. Delivered dialysis was 78% of that prescribed. Patients who had a prescribed or delivered Kt/V < 0.8 varied from 0-44.8%. Mortality rate per year was between 11.3% and 54%. The authors attributed elevated BUN to increased protein intake or inadequate dialysis. Low BUNs may have been due to residual renal function or malnutrition. None of the dialysis parameters correlated with mortality rate except for a Kt/V < 0.8 (p < 0.001) that was directly related to mortality rate. Inadequate dialysis increases mortality rate. PMID- 1457867 TI - Relationship between dialysis induced hypotension and adenosine released by ischemic tissue. AB - Two types of dialysis induced hypotension apparently exist. One type presents as gradually decreasing blood pressure with eventual symptoms (gradual hypotension), whereas the other presents as abruptly and sharply decreasing blood pressure, along with symptoms (abrupt hypotension). In the current study, the authors found that the plasma hypoxanthine concentration during abrupt hypotension was significantly higher than before the hypotension occurred (20 min after saline was administered or at the beginning of dialysis), whereas comparison of the plasma hypoxanthine concentration during gradual hypotension and that before the hypotension occurred (20 min after saline was administered or at the beginning of dialysis) revealed no significant difference. The current results indicate that abnormally increased adenosine triphosphate (ATP) degradation associated with tissue ischemia occurred during abrupt hypotension but not during gradual hypotension. It can be speculated that the increased release of adenosine due to abnormally increased ATP degradation caused the abrupt hypotension. This conclusion seems reasonable given that adenosine directly decreases small vessel tone and inhibits prejunctional release of norepinephrine. PMID- 1457868 TI - Effect of coexistent diseases on survival of patients undergoing dialysis. AB - A cohort retrospective study was used to analyze the effect of comorbidity on survival of end-stage renal disease (ESRD) patients undergoing dialysis. The authors analyzed the survival of 255 patients (144 men, 111 women; median age 54 years; range 8-81 years) followed at the District Hemodialysis Unit in Foggia, Italy, over a 15 year period (median follow-up 30 months; range 1-190 months). Two subscales assessing the overall severity of the identified coexistent diseases and overall physical impairment, and a composite four level index of coexistent diseases (ICED) were assembled using information recorded at the time of admission. The Cox proportional hazard model was applied to evaluate the association of various patient characteristics with the probability of death. Mortality risk was associated with patient age (RR = 3.4 for patients aged 42-61; RR = 4.8 for patients older than age 61 compared with patients younger than age 42), initial condition leading to renal failure (RR = 3.1 for diabetes compared with primary renal disease) and ICED (RR = 3.0 for patients with uncontrolled coexistent disease or severe impairment compared with patients with no coexistent disease and no or mild impairment). Gender and type of dialysis were not associated with mortality risk. It was concluded that, as is the case with other chronic conditions, co-morbidity is a powerful independent prognostic factor in determining the mortality of ESRD patients. PMID- 1457869 TI - Development of an axial flow blood pump LVAS. AB - Nimbus, Inc., (Rancho Cordova, CA) and the University of Pittsburgh (Pittsburgh, PA) are collaborating to develop an implantable rotary blood pump that can be used as a left ventricular assist system (LVAS). The short-term goal of this project is to show that an LVAS based on this pump can operate safely and reliably during chronic implantations in animals. Work conducted to date includes in vitro testing of hydraulic performance, hemolysis, endurance demonstration, and flow visualization. Results indicate that the pump is capable of generating an output of up to 10 L/min at physiologic pressures. Associated electrical power to drive these pumps is in the range of 6-10 watts. One integrated pump was placed in a mock flow loop and operated continuously at a fixed speed (10,000 rpm), pressure (100 mmHg), and flow rate (6 L/min) for 90 days with no apparent difficulty. In vitro hemolysis test results have consistently ranged between 3-6 g of liberated hemoglobin/day, which is an acceptable range for chronic use. Two in vivo trials of 7 and 14 days were performed using calves, after which tests have been done using sheep as the animal model. Five short-term sheep experiments have been conducted with good results. Future studies will include implantations in sheep of 3 months duration. PMID- 1457870 TI - Baylor multipurpose circulatory support system for short- to long-term use. AB - A multipurpose circulatory support system has been developed as both a temporary and permanent device in total artificial hearts (TAHs) and ventricular assist devices (VADs). The multipurpose concept was derived from the development of a totally implantable electromechanical, one-piece TAH. The blood pump is pneumatically driven in short-term use and is electromechanically driven in long term or permanent use. Both TAH and VAD versions consist of the same components, except for the actuation mechanism. The common components are a compact pumping chamber with the same configuration, a blood contacting surface biolized with gelatin, a pusher-plate, a Hexsyn rubber diaphragm (University of Akron, Akron, OH) and bovine pericardial valves. Both TAHs and VADs have 63 ml of stroke volume, and the VADs are compact compared with other available investigational device exemption devices. Currently, 1 week survival has been achieved using the electromechanical TAH and 2 week survival using the electromechanimcal VAD without anticoagulation. Results suggest that the currently developed system could be applied in varied patients as a temporary device after cardiotomy, a long-term device for bridge to transplantation, or a permanent device for end stage heart disease. PMID- 1457871 TI - Electrohydraulic ventricular assist device development. AB - An electrohydraulic ventricular assist device has been developed. An axial flow pump driven by a brushless DC motor provides actuation. Energy is supplied by internal Ni/Cd batteries and by external Ag/Zn batteries, both rechargeable. Electromagnetic induction is used to pass energy through the skin with a transcutaneous energy transfer (TET) system. Physiologic control, battery management, motor commutation, and communication functions are performed by a surface mount internal controller. An infrared data link within the TET coils provides bidirectional communication between the external and internal controllers. A computer model was developed to predict system performance. The dimensions are 180 mm x 116 mm x 40 mm. An in vitro system pumped 5.7 L/min at 10 mmHg inflow and 100 mmHg outflow pressure. The internal battery can provide the projected energy requirements for 40 min after 540 charge/discharge cycles, and the external battery is capable of 4 hr of operation after 150 cycles. The TET system can deliver 60 W of power and exceeds 80% efficiency between 15 and 30 W. The device configuration is based on human cadaver and intraoperative fit trials. The device is being modified for calf implantation by redirecting the blood ports, increasing the output, and incorporating the internal controller in the unified device base. PMID- 1457872 TI - Prolonged extracorporeal circulation without heparin. Evaluation of the Medtronic Minimax oxygenator. AB - Bleeding remains the most common complication of prolonged extracorporeal life support (ECLS). This study evaluated the Medtronic Minimax (Annaheim, CA) microporous oxygenator with the Carmeda Bio Active (heparin bonded) Surface (Stockholm, Sweden) for use in prolonged neonatal ECLS. Eight adult sheep were maintained on venovenous extracorporeal circulation (ECC) for a period of 4 days without systemic heparin. After 4 days of venovenous ECC without anticoagulation, there was no evidence of significant bleeding, circuit thrombosis, or systemic embolism. Gas exchange, hydrodynamic performance, coagulation, and biocompatibility studies suggest that the Minimax is safe and reliable for short term or long-term ECLS in neonates. PMID- 1457873 TI - Rate constants of embolization and quantitation of emboli from the hollow-fiber oxygenator and arterial filter during cardiopulmonary bypass. AB - A direct technique was developed to estimate parameters related to half life (T1/2) and rate constants of embolization (RCE) and to quantitate emboli of three sizes (small, medium, and large) shed from the oxygenator and arterial filter during cardiopulmonary bypass (CPB). Cardiopulmonary bypass was performed in 16 Yorkshire pigs divided as follows: systemic heparin group (SHG:6), systemic heparin/heparinized circuit group (SH/HCG:5), and Iloprost (Bentley) (2 ng/kg/min)/heparinized circuit group (IHCG:5) with In-111 labeled autologous platelets. The anesthetized pigs (20-25 kg) underwent CPB at 2.5-3.0 L/min for 3 hours. Pigs were injected with In-111 platelets (300-420 microCi) 24 hours before CPB. Cardiopulmonary bypass was instituted with a roller pump and hollow-fiber oxygenator, and thrombosis and embolization on the oxygenator and filter were monitored by a calibrated Geiger probe (WMB Johnson Associates, Montvale, NJ). The radioactivity in the oxygenator and filter reached peak values at 25-45 min after CPB; the radioactivity then declined in the oxygenator but remained at a steady state in the filter, suggesting continuous embolization at the same rate of trapping. The curve stripping technique of the normalized radioactivity time curve of the oxygenator was used for RCE estimation of different sized emboli shed from the oxygenator; 42% of thrombus embolized from the oxygenator in SHG with three rate constants, with T1/2s of 12 min, 42 min, and 13 hr; the SH/HCG embolized 35% with T1/2 of 78 min, and the IHCG embolized 30%, with a T1/2 of 22 min. This indicates that there is less embolization in the IHCG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457874 TI - Respiratory dialysis. A new concept in pulmonary support. AB - Use of a new intravenous oxygenator made of hollow fiber membranes arranged around a centrally positioned balloon is reported. In vitro studies using fluorescent image tracking velocimetry and gas exchange analysis demonstrated enhanced convective mixing with balloon pulsations and augmented gas flux (100% increase in pO2) compared with the device in its static configuration. In vivo observations confirmed a greater than 50% increase in O2 flux with balloon activation. Those parameters that produce radial flow and convective mixing in vitro enhance gas flux in vivo, thus confirming the efforts to exceed the fluid limit translate into improved gas exchange. PMID- 1457876 TI - Use of bone char as an adsorbent in preparation of water for dialysis. AB - Currently, deionizers (DI) and reverse osmosis (RO) are used to prepare water for dialysis. When water metal levels increase, for example, with the use of alum, the variation in metal content can reduce RO performance. Pretreatment of water with ethylenediaminetetraacetic acid or alkali can be used to reduce Al fouling. The authors examined adsorption of metal water contaminants with bone char (BRIMAC, Biolab, Oakville, Canada) as a cheaper alternative. Water treatment for the unit consists of a blend valve, 30 mu filter, 2 X 3 cu ft adsorption tanks, 5 mu filter, 30,000 grain automatic water softener, 5 mu filter, Millipore RO 1,000, 2 X 7" mixed bed DI in series, and a polysulfone ultrafilter. During 29 weeks of continuous bone char adsorption, raw water Al ranged from 0.022 to 0.298 ppm (mean, 0.097 +/- 0.075 ppm; cf. the Environmental Protection Agency's proposed drinking water standard of < 0.05 ppm). Postadsorption Al ranged from 0.002 to 0.076 ppm (0.041 +/- 0.04), a decrease of 55-91% (83.0 +/- 8.5%). Final water Al was < 0.001 at all times. No fouling of the RO membrane occurred. Residual chlorine after the first adsorption was < 0.02 to 0.09 ppm. Significant reductions in other metals, notably Pb, Cu, and Zn were noted. Bone char is a cheap, effective, and simple alternative for removing excess trace elements from water for hemodialysis. Further study to evaluate the efficacy of bone char in removing other organic and inorganic water contaminants is needed. PMID- 1457875 TI - Polyunsaturated fatty acids of the n-3 class in chronic dialysis. AB - N-3 PUFAs are believed to 1) reduce serum lipids, 2) modify the complement activating system, 3) increase red blood cell elasticity, and 4) decrease thrombotic events. These four parameters were investigated in 19 chronic stabilized dialysis patients assessed by 1) the control of the serum lipids, 2) the degree of leukopenia 10 minutes after the start of dialysis, 3) the degree of red cell fragmentation (RCF) during dialysis, and 4) the reusability of the dialyzer. The patients were their own controls during four periods: 1) no PUFAs for longer than 6 months, 2) 4 x 425 mg of PUFAs/day for 6 weeks, 3) 6 x 425 mg PUFAs/day for 6 weeks, and 4) no PUFAs during at least 6 weeks. Previous diets and medications remained unchanged. It was concluded that there was no significant effect on serum lipids in the given dosages, and no effect on the degree of leukopenia, red blood cell elasticity or bleeding, and/or antithrombotic activity. No change was seen in insulinemia, fibrinogenemia, or arterial pressure. No serious side effects were noted other than a "fishy aftertaste." PMID- 1457877 TI - Clinical experience with heat sterilization for reprocessing dialyzers. AB - Use of heat sterilization for dialysis reprocessing offers significant advantages over chemical germicides. Polysulfone dialyzers (Fresenius 60M or 80M) can be sterilized by heating to 105 degrees C for 20 hr, thus permitting clinical trials of this method. One hundred eighty patients received 9,000 treatments. Pyrogenic reactions, sepsis, and subjective symptoms have not occurred. In vitro clearances (Qb 500 ml/min, Qd 800 ml/min) at baseline and after 2-8 uses did not differ (340 +/- 29 vs. 352 +/- 4 ml/min, respectively). KoA determined in vivo did not decrease (baseline 709 +/- 131 vs. 7th use 632 +/- 50 ml/min). Kt/V for urea was not different in 18 patients treated with heat sterilized dialyzers over 6 months when compared with a baseline period with formaldehyde sterilized dialyzers (1.37 +/- 0.12 vs. 1.32 +/- 0.11 at similar time and blood flows). Mean use number was 7.4 (dialyzers limited to 11 uses). Of discarded dialyzers, 44% failed a bedside integrity test (blood side pressurized at > 400 mmHg for 1 min), 36% failed automated fiber bundle or pressure holding tests, 8% had a blood leak, and 12% reached 11 uses. Clinical blood leaks occur in < 0.5% of treatments. Heat sterilization is a safe and effective method of dialysis reprocessing, but quality control of the process is essential. Based on initial clinical experience, heat sterilization of dialyzers for reuse is a promising alternative to chemical disinfection. PMID- 1457878 TI - Skeletal muscle powered pumps can work under low preload. Design considerations. AB - Characteristics of a dual chambered, single layered skeletal muscle powered pump (DCSLP) and a single chamber, multilayered pump (SCMLP) made from similar masses of untrained latissimus dorsi muscle (LD) were compared. For the DCSLP, 16 canine LDs (51.5 +/- 1.6 g) were wrapped in a "figure eight" around two parallel mandrels, whereas for the SCMLP, LDs were made in 10 by wrapping the LD (54 +/- 8.5 g) twice around one mandrel. Chamber compliance and pump isovolumic peak developed pressure (PDP), stroke volume (SV), stroke work (SW), and ejection fraction (EF) of single contractions were measured. In six of the DCSLP dogs (LV), heart left ventricular stroke volume (LVSV) and left ventricular stroke work (LVSW) were determined. Stimulation parameters were the same for all. Student's t-test (* = p < 0.05) was used for statistical analysis. Dual chambered, single layered skeletal muscle powered pumps with a diastolic volume/mass ratio of 0.63 were more compliant than SCMLPs with a ratio of 0.37. Single chamber, multilayered pumps generated slightly higher PDP, but this was significant only at 60 mmHg preload. At a preload of 15 and an afterload of 120 mmHg, DCSLPs had higher SV (10.7 +/- 1.1 ml) and SW (0.98 +/- 0.14 x 10(6) ergs) than SCMLPs (6.8 +/- 0.7 ml* and 0.58 +/- 0.08 x 10(6) ergs*), or their LV counterparts (5.3 +/- 0.9 ml and 0.84 +/- 0.22 x 10(6) ergs).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457879 TI - A new thermal shape memory Ti-Ni alloy stent covered with silicone. AB - An attempt was made to develop an airway stent for nonsurgical transluminal implantation using a bronchofiberscope. The stent is composed of a single wire with a diameter of 0.5 mm. The wire is made of thermal shape memory titanium nickel alloy, with a transition temperature of 25-30 degrees C. To avoid direct contact between the metal and the tissue, the wire is covered with a 300 microns thick coating of silicone. The stent is horseshoe shaped in cross-section. It is 15 mm in outer transverse diameter and 40 mm long. Ten stents were implanted in 10 dogs whose tracheal cartilages had been previously broken. The stents were first cooled in ice water to reduce their diameter and then inserted into the target site. The wire was warmed to body temperature and recovered its initial shape within 10 sec. The dogs were killed for examination between 1 week and 6 months after implantation. All the stents were located at the implantation sites and were patent. Tissue reactions, such as ulceration and granulation formation, were less severe than in those with previously implanted non-silicone covered stents. Microscopic observation showed that the wires became gradually covered with epithelium within 2 months. This transluminal technique for preserving airway patency shows promise for clinical application. PMID- 1457880 TI - Evaluation of a continuous thermodilution cardiac output catheter. AB - The authors evaluated a thermodilution catheter designed to continuously measure cardiac output (CO). A 10 cm long surface heating element is positioned in a Swan Ganz catheter corresponding to a right atrial-ventricular site. Heat is repetitively deposited into flowing blood in a unique, pseudorandom binary form. Small temperature fluctuations are sensed with a high performance thermistor and correlated with the heat input pattern, from which CO is determined. Seven adult sheep were anesthetized and instrumented for both continuous and standard cold bolus injection thermodilution (COM1) flow measurements. Heart rate and blood volume were adjusted to vary CO from 1.5 to 13.2 L/min. Continuous measurements correlated well with triplicate COM1 determinations (Sy,x = 0.56, r = 0.967) that improved with experience (Sy,x = 0.38, r = 0.99 for the last three animals). The surface heat transfer coefficient was measured in water (catheter parallel to flow). Results agreed well with a standard cylinder-in-crossflow correlation. The right ventricle heating element surface temperature was predicted for several CO and heating combinations. Worst case results yielded a 5.8 degrees C surface temperature elevation, suggesting that thermally induced damage is unlikely. Results suggest this catheter provides accuracy at least comparable to that of standard cold bolus injection methods, with no heat induced damage to blood. PMID- 1457881 TI - Development of a polyepoxy compound cross-linked heterologous connective tissue tube. AB - A heterologous connective tissue tube with "built-in" polyester mesh was developed using a rabbit subcutaneous tissue and polyepoxy compound cross-linking method. To evaluate the graft, 11 grafts were implanted end to end in the position of the thoracic aorta of 11 dogs and evaluated from 1 hr to 80 days after surgery. The graft was white and pliable, and the mesh was seen through the connective tissue. The handling characteristics were good, and no bleeding was observed from either the graft wall or suture holes. Macroscopically, at 1 hour, the luminal surface was covered with a thin thrombus layer. At 80 days, most of the inner surface of the explanted graft was white and shiny without irregularity, but a small area of blood stain was observed. Microscopically, fibroblasts were observed in the graft wall at 7 days; capillaries penetrating to the luminal surface appeared at 29 days. Bleeding was rarely observed around the fabric. A layer of donor connective tissue was still observed at 80 days. No foreign body reaction was observed except around the mesh. It was concluded that the graft healed well and could be an arterial substitute. PMID- 1457882 TI - Development of an implantable centrifugal blood pump. AB - The efficacy of centrifugal pumps for short-term (0-30 days) ventricular support has been widely reported and favorably compared with pulsatile systems. A small, durable, implantable centrifugal blood pump is being developed for medium-term use (up to 6 months). The pump is based on the Medtronic Hemadyne system that has existed in multiple forms over the past 30 years. The pump is approximately the size of a tennis ball, weighs 240 g, and is comprised of a 2.5 cm plastic impeller driven by a radially coupled brushless DC motor. In vitro hydraulic performance was recorded over a wide range of flow conditions on a mock circulatory loop. The pump generated 7 L/min flow against an afterload of 100 mmHg pressure, with a maximum power draw of 10.4 watts. Pulsatile flow was preserved when placed in conjunction with a simulated left ventricle. In vivo testing was performed in 10 healthy sheep for 10-292 hr. Heparin was used to facilitate cannulation, and no anticoagulation was administered after pump implantation. Blood chemistries reflecting hematologic, pulmonary, renal, and hepatic functions were recorded and demonstrated no adverse effects with normal pump operation. Complications were related to kinking of blood conduits and thrombus formation within the cannulae. These results are encouraging and warrant further studies to prove feasibility of this pump as a medium-term implantable ventricular assist device. PMID- 1457883 TI - Pulmonary function in a non-pulsatile pulmonary circulation. AB - The authors suggested that a mammal immediately accommodates well to nonpulsatile flow in the systemic circulation. In the current study, nonpulsatile pulmonary blood flow using a centrifugal pump was established in chronic models to analyze its influence on the pulmonary circulation. A pulsatile right ventricular assist device (RVAD) was implanted to draw blood from both the right atrium and ventricle and send blood to the pulmonary artery in six goats. After 2 weeks, the pulsatile pump was quickly replaced with a centrifugal pump without anesthesia, and a 100% non-pulsatile pulmonary blood flow was obtained. Cardiac output was kept at 80-120 ml/kg/min during the experiments. No changes were observed in hemodynamic parameters, including pulmonary arterial pressure, pulmonary vascular resistance index, and blood gas data, after the immediate depulsation of the pulmonary blood flow. There was also no significant change in the ventral to dorsal tissue blood flow ratio of the lower lobe of the right lung, which was calculated by a colored microsphere method, between pulsatile and non-pulsatile pulmonary blood perfusion. These results suggest that pulmonary function, including blood flow distribution, is not affected by non-pulsatile pulmonary circulation for periods up to 14 days. PMID- 1457884 TI - Toxicity of heat sterilized peritoneal dialysis fluids is derived from degradation of glucose. AB - Heat sterilization makes peritoneal dialysis (PD) solutions cytotoxic. Two compounds in the solutions, lactate and glucose, can be degraded by heat. This study's goal was to discover which of the compounds was responsible for the cytotoxicity. The influence of sterilization temperature on degradation of the compounds was also subjected to investigation. Solutions of glucose and lactate and a mixture of lactate and glucose were prepared. These were sterilized in glass ampules in an oil bath at different temperatures for varying times. Toxicity was determined as inhibition of cell growth with a fibroblast cell line (L929), and ultraviolet (UV) absorbance was measured at 284 nm. Lactate solutions did not show cytotoxicity after heat sterilization. Glucose solutions that were heat sterilized showed an increase in UV absorbance at 284 nm and were cytotoxic. The mixture of lactate and glucose exhibited the same cytotoxicity as glucose alone. Lower sterilization temperatures lead to increased cytotoxicity and an increase in UV absorbance at 284 nm. Results indicate that the toxic products formed during heat sterilization of PD fluids are derived from glucose. PMID- 1457885 TI - Estimation of urea and creatinine clearance in peritoneal dialysis. AB - The authors performed peritoneal equilibration tests (PET) in children and young adults of widely varying sizes to characterize membrane transport type, and used data (D/P ratios) obtained to predict clearances of urea (KT/Vurea) and creatinine (CrCl). Overall, PET predicted and measured values for KT/Vurea and CrCl were not significantly different. KT/Vurea could be reliably predicted from PET data for all membrane transport types. However, the relationship between predicted and measured CrCl was only significant for patients with high and high average membrane transport. In addition, the relationship between KT/Vurea and CrCl was significant only in patients with high and high average membrane transport. PMID- 1457886 TI - Development of continuous recirculating peritoneal dialysis using a double lumen catheter. AB - Continuous recirculating peritoneal dialysis (CRPD) was newly introduced to improve solute removal efficiency in conventional dialysis therapies such as hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). In CRPD, a part of the dialysate in the peritoneal cavity was drained through a double lumen catheter and purified by an extracorporeal dialyzer. Urea removal characteristics in CRPD were examined in a canine study. In this study, a recirculation-dialysis experiment using a dog weighing 9.0 kg was carried out under 100 and 200 ml/min of flow for recirculating and delivered dialysates, respectively. An FB-50H (Nipro Medical Industries, Ltd., Osaka, Japan) composed of cellulose diacetate membrane with 0.5 m2 of surface area and Dianeal-1.5 (Baxter Limited Laboratories, Tokyo, Japan) containing urea were used as the extracorporeal dialyzer and dialysate. Urea peritoneal and dialyzer dialysances (DBP and DBD) were 3.05 and 33.3 ml/min by computer simulation using a compartment model for CRPD. This DBP value can be estimated as 20.3 ml/min for a 60 kg human. From this result, time-averaged value for BUN over an 8 hr/day CRPD, combined with three exchanges/day as CAPD is estimated to be 34.3 mg/dl, which is much lower than 45.2 mg/dl for a 12 hr/week HD, or 53.0 mg/dl for conventional CAPD. PMID- 1457887 TI - Two-dimensional orientational response of smooth muscle cells to cyclic stretching. AB - It was hypothesized that an orientated cellular tissue for incorporation into vital, functioning hybrid artificial organs can be prepared by periodically applying mechanical stresses on a hybrid tissue. Therefore, the effect of cyclic stretching on the two-dimensional (2-D) orientation response of arterial smooth muscle cells (SMCs) was studied. Smooth muscle cells derived from bovine aortas were seeded onto transparent elastomeric membranes made of polyurethane, and subjected to periodical stretching with various amplitudes from 5-20% at frequencies of 15 to 120 RPM for up to 24 hours. Phase-contrast microscopic views of SMCs were time-lapse video recorded. The orientation angle to the direction of stretching (OA) and cellular longitudinal length (CLL) of individual cells were analyzed by a computerized image processor. After several hours, SMCs subjected to the stress exhibited orientation responses perpendicular to the direction of stretching, evidenced by a significant increase in OA. The responses were more rapid under operating conditions with higher amplitudes and frequencies of stretching. Meanwhile, little significant change in CLL was observed. These findings indicate that an applied mechanical stress induces a significant orientation response, without morphologic alteration of SMCs. The mechanically induced orientation response provides a fundamental basis for more structured hybrid organs and tissue engineering. PMID- 1457888 TI - Inflammatory reaction induced by agarose implants reduced by adding adrenal cells to the polymer. AB - Microencapsulation of adrenal cells is proposed for reducing the non-specific inflammatory reaction observed around polymer implants. This hypothesis was tested by comparing both host cellular reaction and the surrounding graft cell populations that appeared when either agarose embedded cells or empty agarose beads were implanted. The authors' results showed that the fibrotic material that surrounded the implanted empty agarose microbeads was not as severe when adrenal cells were present. Similarly, the T lymphocyte population surrounding the graft was considerably reduced, along with the percentage of CD4 and CD8 positive cell subpopulations. The activation macrophage marker IaD disappeared. The authors' results support the hypothesis that embedded adrenal cells may be a suitable solution for reducing early inflammatory events due to microcapsule implantation. PMID- 1457889 TI - Evaluation of the biocompatibility of a new method for heparin coating of a cardiopulmonary bypass circuit. AB - The biocompatibility of the Terumo (Terumo Corporation, Tokyo, Japan) covalent heparin coating method in a cardiopulmonary bypass (CPB) circuit was evaluated in ex vivo and in vivo experiments. In the ex vivo experiment, fresh human heparinized blood primed both a miniature heparin coated circuit (HCC) and the identical noncoated circuit (NCC), and was circulated simultaneously for 2 hr (n = 6). In the in vivo experiment, 10 rabbits underwent 2 hr of CPB under systemic heparinization (ACT > 400 sec) with HCC (n = 5) and with NCC (n = 5). In the ex vivo study, thrombin/anti-thrombin III complex, thromboglobulin, platelet factor IV, granulocyte elastase, and C3a were significantly lower in the HCC than in the NCC at 60 and 120 min of circulation (p < 0.05). In the in vivo study, platelet counts (percent of value at 10 min of CPB) were significantly higher in the HCC than NCC (HCC:NCC 87 +/- 10:71 +/- 12 at 60 min, 81 +/- 17:56 +/- 16 at 120 min). Scanning electron microscopic examination of the circuits showed less significant adhesion and pseudopod formation of platelets in the HCC than NCC in both ex vivo and in vivo situations. These results demonstrate that this heparin coated CPB circuit provides superior biocompatibility compared with a noncoated circuit by reducing the activation of the coagulation cascade, platelets, leukocytes, and complement. PMID- 1457890 TI - Plasma leakage through microporous membranes. Role of phospholipids. AB - Plasma leakage through microporous membrane oxygenators is a well known complication of prolonged extracorporeal circulation. The authors hypothesized that adsorption of bipolar plasma molecules, such as phospholipids on the microporous membrane, results in formation of a hydrophilic layer over the hydrophobic surface of the membrane; this, in turn, leads to plasma leakage at normal surface tensions. A lipid phosphorus assay was used to measure phospholipid adsorption onto the fibers of microporous membrane oxygenators tested under a variety of experimental conditions. Adsorption of phospholipids on the microporous membrane was concentration dependent. Reproducible plasma leakage occurred both in vitro and in vivo, and the time to leakage was dependent on the concentration of phospholipids adsorbed upon the microporous membrane. Based upon these results, the authors conclude that adsorption of phospholipids contributes to the development of plasma leakage through microporous membrane oxygenators. PMID- 1457891 TI - Laboratory experience with a novel, non-occlusive, pressure-regulated peristaltic blood pump. AB - Current blood pumps have potential safety problems, including the ability to generate extreme positive and negative pressures. These problems were addressed in the design and testing of a non-occlusive, peristaltic blood pump. The pump consists of a tubing of unique design (pump chamber) wrapped under tension around a rotor with rollers. The pump chamber design is such that the pump is passively filling; flow is dependent upon the pressure of the blood supply and the size of the pump chamber. Thus, negative pressures cannot be generated. With the outlet occluded, the pump produces the maximum attainable pressure, which can be set by adjusting the tension of the pump chamber around the rollers. The design characteristics make the pump suitable for prolonged use. The pump was tested in vitro for pressure safety, hemolysis, and durability. The pump prototype was used in 25 experiments involving extracorporeal circulation on sheep, with an average duration of approximately 6 hr and bypass flow rates between 0.5 and 2.0 L/min. No pump related complications occurred in any of these experiments. The pump described here is suitable for short- and long-term perfusion applications, and does not require additional pressure regulation, as do current blood pumps. PMID- 1457892 TI - Tissue viability measurement by in situ fluorometry. AB - A prototype laser-fiber optic based sensor for in situ monitoring of nicotinamide adenine dinucleotide (NADH) has been developed. This system is based on a compact neodymium-yttrium-aluminum-garnet (Nd:YAG) laser with associated harmonic generators. Light distribution to and from tissue is handled by a fiber optic network, including a long optical fiber to be inserted into the target tissue. Immobilizing the enzyme lactate dehydrogenase on the fiber tip converts the monitoring channel into a lactate sensor. A new dual beam reflection approach for blood volume artifact compensation is tested. Detection sensitivity of free NADH in the micromolar region is achieved. The method and system configuration appear feasible for continuous in situ monitoring of two important indices of ischemia and hypoxia in a clinical setting. PMID- 1457893 TI - Subcutaneous capillary filtrate collector for measurement of blood glucose. AB - The capillary filtrate collector (CFC) is a device that creates an ultrafiltrate at 50-100 microliters/h from subcutaneous capillaries, and carries this filtrate out of the body for chemical analysis. From inside out, components include three looped hollow fiber ultrafiltration membranes, a polytetrafluoroethylene (PTFE) cuff, polyurethane tubing, a "Y" connector leading to a sampling port, a hub, and a needle placed into a 5 ml vacutainer tube. Animal studies have demonstrated that the CFC filtrate glucose level is exactly that of blood at the time the filtrate is created. The authors have performed clinical trials to determine the correlation of blood glucose and CFC glucose levels, and the time delay between contemporary samples. Seven diabetic patients wore the CFC device, tubing, and vacutainer tube for 1 month. In home monitored diabetic patients, fingerstick glucose measurements were performed at the usual daily schedule. The vacutainer was then evacuated, and this average sample analyzed and compared with the average of prior blood glucose levels. An optical device then was applied to measure the linear velocity of CFC fluid through external tubing, and predict the time for fluid to pass from fibers to the sampling port (average, 25 min). Capillary filtrate collector samples drawn at this time had glucose concentrations that generally correlated with blood levels. In diabetic patients on hemodialysis, the vacutainer was evacuated at the start of each treatment, and CFC and blood samples were drawn every 20 min during the treatment. Comparison of glucose-versus-time curves indicated a reasonable correlation between blood and CFC samples, with a delay related to flow rate (which declined 50% during dialysis).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457894 TI - Surface fixation of hydrogels. Heparin and glucose oxidase hydrogelated surfaces. AB - The authors report a new photochemical technique for the fixation of hydrogels onto the surface of fabricated devices and sensors. The preparative method is based on two different types of photochemistry: photocross-linking due to intermolecular photodimerization of cinnamoyl groups, and photoinduced covalent bonding due to the photoreactivity of azido groups. The immobilization of heparin, useful as a thromboresistant coating, onto poly(ethylene terephthalate), and the immobilization of glucose oxidase onto the surface of a carbon fiber electrode, were demonstrated. In the former, immobilized heparin was found to be continuously released from the hydrogel, and the release rate was effectively controlled by the thickness of the hydrogel. In the latter, upon the addition of glucose, a spontaneous electrical response was observed to function as a glucose sensor. No delamination was found for either system after vigorous washing with water. Thus, durable surface hydrogelation, simultaneous immobilization of bioactive substances, and functioning of the systems were demonstrated. PMID- 1457896 TI - In search of sterile, endotoxin-free dialysate. AB - Sterile dialysate, free of endotoxin (ET) and other cytokine inducing factors, will probably become a future standard. High-flux dialysis with bicarbonate and reuse has the membrane, the pressures, and bacteriologic potential for ET fragments to pass from dialysate to the blood side of the membrane with activation of monocytes and production of cytokines. Ultrafiltration through polysulfone filters has been shown to remove bacteria, ET, and its fragments and other cytotoxic inducing factors. The authors found that in spite of sterile, ET free, reverse osmosis (RO) water, ET was usually present at the dialyzer inlet and arose from the RO storage tank water with bacteria < 30 CFU/ml, in spite of repeated disinfection. The authors now remove bacteria, ET, and fragments from RO tank water with a 5 mu cellulose filter followed by ultrafiltration with a Fresenius F-80 polysulfone dialyzer inserted between the wall RO delivery port and each delivery system. At the dialyzer inlet, monthly bacterial counts were < 30 cfu/ml, and ET values (n = 38) were not detectable in 89% and < 0.5 EU/ml in 11%. The F-80 filters were used for 180+ dialyses along with the 5 mu filters, which replaced the frequently endotoxin contaminated 10 mu filters in the Monitral-S delivery systems. The costs did not increase. PMID- 1457895 TI - A blood pump with an interatrial shunt for use as an electrohydraulic total artificial heart. AB - A recently designed blood pump subsystem for the completely implantable electrohydraulic total artificial heart (EHTAH) has been developed and is under evaluation. The subsystem consists of joined left and right ventricles, atrial cuffs with an interatrial shunt (IAS), and two outflow grafts. The ventricles were developed to fit within the pericardial space based on the results of anatomic fit trials. An optimized configuration for animal use, which was adaptable for human use with minimal modification, was identified. The core dimensions of the ventricles with an energy converter are approximately 10 x 11 x 7 cm. Maximum output and stroke volume are 9.2 L/min and 81 ml, respectively. The IAS is used to balance the volumetrically coupled EHTAH, and is made by forming an orifice in the common septum of the left and right atrial cuffs. Performance and durability of the IAS were examined in animal experiments for up to 9 days. The diameter of the IAS was 3.4-5.5 mm, and the left-right atrial pressure difference ranged from 2 to 10 mmHg, with 0.57-1.48 L/min of theoretically calculated shunt flow. No evidence of thrombus formation was found in or around the IAS at autopsy. The entire EHTAH system with a new blood pump is being assembled for long-term animal studies. PMID- 1457897 TI - LDL apheresis in atherosclerotic disease with hyperlipidemia. AB - Low density lipoprotein (LDL) apheresis was carried out in 28 atherosclerotic patients with clinical signs of poor peripheral circulation and abnormally high LDL levels. The LDL apheresis using extracorporeal adsorption with a dextran sulfate cellulose column (Liposorber, Kaneka, Japan) was done 10 times over 3 months. Hyperlipidemia was rapidly corrected after the initial two aphereses, whereas clinical signs of arteriosclerosis obliterans (ASO), such as coldness of the legs in 17 of 19 patients (89.5%), intermittent claudication in 14 of 17 patients (82.4%), foot pain at rest in 15 of 18 patients (83.3%), poor arterial pulsation in 12 of 16 patients (75.0%), and diminution of ulcer/necrosis in 3 of 5 patients (60.0%), improved in parallel. Improvement in plethysmographic and thermographic findings were observed in 10 of 10 patients (100.0%) and 13 of 14 patients (92.9%), respectively. Our tentative conclusion is that LDL apheresis using the Liposorber system was very effective in removing LDL from blood, and clinical symptoms rapidly improved in all patients concomitant with a reduction in plasma LDL levels. Hyperlipidemia may be a risk factor for symptomatic ASO in the lower extremities, and its active correction may be worth trying. PMID- 1457898 TI - The efficiency of new leukocyte removal filters. CF-1 and CF-2. AB - Two new leukocyte removal filters, Nipro CF-1 and CF-2 (Nipo Medical Industries, Osaka, Japan), were evaluated. These non-woven polyester filters, which are gravity flow devices that require no priming and no rinsing after use, were developed for preparing 400 ml of whole blood or red cell concentrates from 400 ml of whole blood. A flow cytometric technique was developed to measure extremely low white blood cell (WBC) counts. To evaluate the efficiency of these filters, leukocyte counts were measured by three techniques: 1) electronic, 2) visual, and 3) flow cytometry. Flow cytometric counting was done using a Coulter EPICS-C cytometer (Coulter Corp., Hialeah, FL). Nipro CF-1 removed 99.97 +/- 0.01% (mean +/- SD, n = 14) of leukocytes measured by flow cytometry, and CF-1 recovered 90.7 +/- 4.47% (n = 21) of red blood cells. After filtration through CF-2, more than a 6 log10 (> 99.9999%) depletion of WBCs was detected in six samples, a 6 log10 (99.9999%) depletion of WBCs was detected in two samples, a 5 log10 (99.999%) depletion was detected in five samples, and a 4 log10 (99.99%) depletion was detected in one sample. CF-1, in which size and priming volume was smaller than other commercial leukocyte removal filters, accomplished a 3 log10 reduction in WBC count, compared with other commercial filters. CF-2 achieved a 4-6 log10 depletion of WBCs assayed by flow cytometry. PMID- 1457899 TI - In vitro perfusion of hybrid artificial pancreas devices at low flow rates. AB - Type I diabetes is characterized by insulin insufficiency due to lack of functional beta cells. To replace injection therapy, schemes such as the Hybrid Artificial Pancreas (HAP) were developed. This consists of an acrylic housing enclosing a semipermeable hollow fiber membrane. Donor islets can be seeded in the annular space through a port in the housing, and thus are separated from the recipient's bloodstream or perfusate. Before scaling the HAP to human size, the dynamics of its insulin response to a perfusion glucose challenge must be better understood. In this study, the HAP's insulin response after a step increase in the lumenal glucose concentration was determined as a function of the radial thickness of the annular space (0.173-0.973 mm) and islet distribution at a flow rate of 1 ml/min. Devices containing a single, 65 mm long fiber were used. Rat islets were isolated using standard collagenase digestion techniques. In unseeded HAP perfusions, the washout time for glucose and insulin from the annular space was dependent on flow rate and radial thickness. Both solutes were removed in < 3 min from the smallest devices when perfused at 10 ml/min. Thus, solute transport within the HAP is very fast. In the seeded HAP perfusions, the devices were subjected to a step increase in the lumenal glucose concentration. Sequential samples of the HAP effluent were collected and assayed for glucose and insulin. The spatial distribution of the islets in the annular space was one of the most important factors in determining the HAP's insulin response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457900 TI - Islet transplantation using an immunoprotective membrane in dogs that have undergone a pancreatectomy. AB - The use of a selectively permeable membrane to transplant nonsyngeneic tissue without accompanying immunosuppressive therapy has been investigated using two approaches. The first hybrid artificial pancreas is implanted as a vascular shunt in which blood circulates through the lumen of a tubular membrane. The islet tissue is distributed within a chamber surrounding the membrane enclosed by an acrylic housing. Studies with diabetic dogs that have had pancreatectomies have demonstrated that these devices could replace exogenous insulin therapy for at least 6 months in five animals. This report presents data on two of these dogs, demonstrating viability and function of the transplanted tissue after 1 year. As an alternative to the vascular device, islets sealed within cylindrical permselective membrane chambers have been implanted in the peritoneum. Preliminary data from three dogs indicate that the nonvascular implants can also regulate fasting glucose levels in the diabetic dog model. PMID- 1457901 TI - The spring-driven implantable pump. A low-cost alternative. AB - In the current era of cost containment in medicine, manufacturing economics have become increasingly important. The authors devised an implantable pump powered by spring force from an elastomeric Belleville washer, which is also the outer flexible wall of the drug reservoir. Use of formed and injection molded parts provides for low-cost manufacturing, in contrast to the precision welded alternative designs. Additional advantages include insensitivity to changes in ambient temperature and pressure. Finite element modeling of the elastomer spring allows prediction of the effects of parameter changes on performance, so that expansions and reductions of scale can be made without compromising the uniform spring rate of the device. A concern that subcutaneous fibrous encapsulation might markedly alter reservoir pressure was not supported by experimental data. In a unit implanted subcutaneously in a dog, reservoir pressures measured over a 4 year period were stable. This new, simple, implantable infusion pump can serve as an economical vehicle for prolonged parenteral drug treatment of ambulatory subjects in circumstances where continuous single-rate infusion is appropriate. PMID- 1457902 TI - Glucose-sensitive membrane and infrared absorption spectroscopy for potential use as an implantable glucose sensor. AB - The applicability of using infrared absorption spectroscopy for an implantable glucose sensor was tested by measuring absorbance at 9.66 microns for glucose in aqueous solution at known concentrations. A commercial Fourier transform infrared spectrometer was used with an attenuated total reflection technique (ATR). Absorbance measurements were reproducible and linearity was excellent (coefficient of correlation: 0.996), in spite of pH and temperature changes over values that span the human physiologic ranges (pH 6.8-7.8, temperature, 32-43 degrees C) and 18-34% decreases in incident infrared energy. The minimum detectable concentration of glucose, however, was 31 mmol/L (560 mg/d) and, to use infrared sources and detectors compatible with an implantable device, an absorbance peak between 1 and 3 microns must be used. To solve the detection sensitivity and wavelength problems, the ATR prism was coated with a hydrophobic liquid membrane. The absorbance of water varied at 2.95 microns in inverse linear proportion to glucose concentration between 2-31 mmol/L (35-560 mg/dL, r = 0.992). Estimated incident infrared energy at 2.95 microns (0.2 micron bandwidth) was low enough to theoretically allow the use of a lithium battery small enough for implantation. These findings support the concept of using infrared absorption spectroscopy for an implantable glucose sensor. PMID- 1457903 TI - Immunoprotection of xenocytes in a hollow fiber bioartificial liver. AB - A new, hollow fiber bioartificial liver (BAL) was tested in an anhepatic rabbit model to assess the hollow fiber membrane as an immunologic barrier. The extracorporeal BAL contained rat hepatocytes (xenocytes) entrapped in collagen gel inside the lumen of hollow fibers with 100 kd nominal molecular weight cut off. Blood from the anhepatic rabbit flowed in the extracapillary compartment. After 4 h of BAL hemoperfusion, the hepatocyte gels were tested for evidence of rabbit immunoglobulin and complement. Samples of the gels were stained with fluorescein isothiocyanate (FITC)-labeled antibodies directed against rabbit IgM, rabbit IgG (Fc and F[ab]2), and rabbit complement (C3) and studied by immunofluorescence microscopy. Enzyme-linked immunosorbent assay and Western blotting were used, respectively, to quantify and identify proteins inside the BAL and in the rabbit blood. These studies suggest that very little rabbit IgG (primarily fragments of IgG) and no IgM or C3 crossed the hollow fibers during hemoperfusion. Rat albumin steadily accumulated in the rabbit blood during hemoperfusion, which indicated membrane permeability to molecules of that size and stable hepatocyte function by the BAL. The authors conclude that hollow fibers with 100 kd nominal molecular weight cut-off provide immunoprotection for xenocytes in an extracorporeal BAL. PMID- 1457904 TI - Does a porcine hepatocyte hybrid artificial liver prolong the survival time of anhepatic rabbits? AB - To examine cultured porcine hepatocytes as a bioreactor of a hybrid artificial liver (HAL) in rabbits, a small version of a multiplated HAL was manufactured. In vitro and ex vivo studies were performed to evaluate the small HAL. The HAL consisted of 50 glass plates (10 x 5 x 0.04 cm each) on which porcine hepatocytes were cultured in a monolayer at confluent cell density. After 2 days of standard cultivation, the glass plates with hepatocytes were placed in the module and were used for studies. The module contains about 5 grams of hepatocytes (1/10 of 2 kg.bw rabbit liver). After undergoing perfusion culture for 5 days, the HAL showed satisfactory hepatic function. Glucose and urea were synthesized at the rate of 4.06 +/- 0.7 mg/module/hr and 0.62 +/- 0.09 mg/module/hr, respectively, and loaded ammonia was metabolized at the rate of 1.29 +/- 0.26 mg/module/hr. Ex vivo extracorporeal plasma perfusion studies revealed that the module with cultured porcine hepatocytes, which were heterogeneous to rabbits, showed a tendency to prolong the survival time of anhepatic rabbits. These results indicate that the HAL system, using multiplated porcine hepatocyte monolayers, is a promising artificial liver support system for clinical cases. PMID- 1457905 TI - Effects of left ventricular pressure unloading during LVAD support on right ventricular contractility. AB - The effects of left ventricular pressure (LVP) unloading with a left ventricular assist device (LVAD) on right ventricular (RV) end-systolic pressure volume relationships were studied. A Thoratec (Berkeley, CA) LVAD was implanted in open chest anesthetized pigs via apical cannulation, and an electromagnetic flow probe and computer controlled pneumatic occluder were attached to the pulmonary artery. RV and left ventricular (LV) pressures were measured with Millar catheters, and changes in RV volume during ejection were determined by integrating the flow signal. As an index of contractility, RV maximal systolic elastance (Emax) was calculated as the slope of the end systolic, pressure volume relationship between an isovolumic beat and a series of transiently occluded beats at different times in the ejection phase. After an 83 +/- 15% decrease in LV pressure time integral during LVAD pumping, there were no significant changes in cardiac output, mean systemic arterial pressure, or in RV dP/dtmax. Most important, RV Emax during LVAD unloading (0.63 +/- 0.16 mmHg/ml) was unchanged from control (0.62 +/- 0.10 mmHg/ml). Therefore, in the normal intact porcine heart, the effective contractility of the right ventricle is not altered by significant LV pressure unloading produced with a LVAD. PMID- 1457906 TI - Effects of uremia and dialysis on brain electrophysiology after recombinant erythropoietin treatment. AB - Quantitative electrophysiologic assessments are sensitive and useful indices of clinical state, and they are valuable in evaluating brain electrical activity before and after recombinant human erythropoietin (r-HuEPO) treatment. To study the hypothesis that, theoretically, anemia might be a cause of brain dysfunction in uremia, the authors assessed 18 patients (10 men and 8 women) on hemodialysis (RDT, age range, 35-58 years) before treatment (T1), and after 12 weeks (T2) and 24 weeks (T3) of r-HuEPO treatment, utilizing the following electrophysiologic tests: visual evoked potentials (VEP), brainstem auditory evoked responses (BAER), and somatosensory evoked potentials (SEP). The r-HuEPO was injected subcutaneously two times a week after RDT to produce hematocrit (Hct) levels of 30-35%. This drug induced a decrement of latency in P100 VEP (134.2 +/- 7.9 msec in T1 versus 116.5 +/- 6.9 msec in T2, p < 0.001, and versus 107.6 +/- 5.7 msec in T3, p < 0.005) and in the four main components of BAER. The most significant SEP changes were P27-N35 from peroneal nerve (p < 0.01), as an augmentation of SEP amplitude. Correction of anemia with r-HuEPO leads to a significant improvement in brain function in patients on RDT. The increased Hct level leads to enhanced brain oxygen delivery, directly improving brain metabolism. When the Hct rises, cerebral blood flow falls from high levels to normal, decreasing delivery of uremic "toxins" to the brain. The decrease in cerebral blood flow may decrease intracranial pressure and, in this way, may exert its beneficial effects by a rheologic pathway. PMID- 1457907 TI - Dialysis leg cramps. Efficacy of quinine versus vitamin E. AB - A controlled randomized double-blind study was done to determine the frequency and severity of leg cramps in 40 patients on dialysis with a history of leg cramps. All patients entered a 2 month placebo washout and were randomized into a 2 month double-dummy phase of quinine 325 mg at bedtime versus vitamin E 400 IU at bedtime. Of the 29 patients completing the study, 16 received quinine and 13 vitamin E. During placebo washout, the vitamin E group had a mean of 10.4 leg cramps per month, and the quinine group had a mean of 10.9. The vitamin E and quinine groups had a 1 month reduction in leg cramps to 3.3 and 3.6, respectively (p < 0.0005 for both groups combined); this was sustained at 2 months. A severity of pain index showed a statistically significant decrease for both groups. The 95% confidence interval for the difference between the number of leg cramps after vitamin E versus quinine treatment (95% confidence interval, -3.8, +3.2) suggests similar efficacy. Quinine and vitamin E were effective treatments for leg cramps in these patients. Considering the potential toxicity of quinine, vitamin E is recommended as the initial treatment of choice for patients on dialysis with leg cramps. PMID- 1457908 TI - Registry report. Use of total artificial hearts: summary of world experience, 1969-1991. AB - Eleven models of total artificial hearts (TAHs) have been used for transient or permanent circulatory support in patients with failing hearts. From April 4, 1969 to July 1, 1991, 230 TAHs were used in 226 patients (four patients received a second TAH) at 39 centers worldwide. Five patients received a Symbion TAH as a permanent circulatory support device; the remaining 221 received TAHs as bridges to cardiac transplantation. The principal investigators received written requests for demographic and clinical information after each implant and annually thereafter to assess survival. The mean patient age (+/- SD) was 43 +/- 12 years (range, 13-69 years); 88% of patients were men. The primary indications for implantation were deterioration while on a transplant waiting list (34%) and acute cardiogenic shock (33%). The duration of implantation ranged from < 1 to 603 days; 65% received heart transplants. The incidence of infection and embolic events occurring during implantation times were 36% and 9%, respectively (stroke, 5%; transient ischemic attacks 4%). Most deaths were caused by sepsis (33%) and multiorgan failure (32%) during the implantation period; sepsis (36%) and rejection of the donor heart (19%) were responsible for most deaths in patients who died after transplantation. The 1 year survival rate was 37% for all patients receiving a device and 50% for those who received a transplanted organ. In the overall Symbion TAH population (187 patients), 40% survived 1 year and 56% of the transplanted group survived 1 year; 39 non-Symbion TAH implants resulted in one long-term survivor (3%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457909 TI - Effects of mechanical ventilation and spontaneous respiration on hemodynamics in calves with total artificial hearts. AB - The effects of respiration on hemodynamics were evaluated in four Holstein calves with total artificial hearts (TAH). The electrohydraulic actuated E4T-TAH has a continuously reciprocating actuator packaged between two alternately ejecting blood pumps that passively fill. The hemodynamic parameters (right atrial pressure [RAP], left atrial pressure [LAP], pulmonary artery pressure [PAP], aortic pressure [AoP]), and right and left pump filling (Rt% fill and Lt% fill) were measured when the animal was intubated and mechanically ventilated. These measurements were repeated with spontaneous respiration after the animal was extubated. With mechanical ventilation, LAP, PAP, and AoP were significantly higher during inspiration than during expiration. However, RAP during inspiration was slightly lower than that during expiration. The Rt% fill during inspiration was significantly lower than during expiration, but Lt% fill during inspiration was significantly higher than during expiration. During spontaneous respiration, these changes were opposite to those observed during mechanical ventilation. That mechanical ventilation generates positive intrathoracic pressure during inspiration, but spontaneous respiration generates negative pressure may explain these results. The change in venous return to the right atrium caused the change in RAP to be opposite in direction to that of the other pressures. PMID- 1457910 TI - Initial in vivo tests of an electrohydraulic actuated total artificial heart. AB - The authors are involved in developing a total artificial heart (TAH) for permanent human use. This device was designed to fit human anatomy, and it has housings made of carbon fiber-epoxy composite and titanium. Tissue valves and protein coating of blood contacting surfaces minimize the need for anticoagulants. A continuously reciprocating electrohydraulic actuator is packaged between two alternately ejecting and passively filling ventricles. The control system varies the pump rate to maintain average left ventricular filling at 90%. This TAH in vivo successively progressed through 1, 5, 9, and 45 day implants in calves of 84, 94, 82, and 82 kg preoperative body weights. The operating modes include automatic and fixed rate. The chronic and acute effects of varying the right pump displaced stroke volume indicated the need for it to be limited to 85% of that of the left for stable hemodynamics at maximum flow. The pump exhibited afterload insensitive and preload sensitive performance. Pump output ranged from 4.0-9.5 L/min at left atrial pressures of 7-16 mmHg at pump rates of 80-160 beats/min in these four experiments. These data suggest that this device will meet clinical hemodynamic requirements; it has the potential for total implantable cardiac replacement. PMID- 1457911 TI - Experimental studies of pulsatile flow and endothelial cell adaptation in ventricle shaped cell culture chambers. AB - The authors' long-term research goal is to minimize the risk of thromboembolic complications in cardiac prostheses by lining blood contacting surfaces with a functional monolayer of autologous endothelial cells. These cells recognize changes in hemodynamics and can adapt effectively to experimentally manipulated flow conditions. By implication, the morphology of endothelial cells, in conjunction with their function, might serve as an indicator of the flow patterns in a particular location. It was hypothesized that, by understanding flow patterns at a given site, the local morphology and function of the endothelial cells in such a region could be predicted. To test this hypothesis, a series of ventricle shaped flow chambers were designed and perfused with pulsatile flow. The flow field in the chambers was studied by computer aided dye visualization and nuclear scintigraphy. The results showed that the large scale motion of the fluid in the cavity was highly coherent and consisted of distinct flow patterns. The temporal and spatial characteristics of the flow patterns, and their implications with respect to endothelial cell endurance in this in vitro environment, were examined in detail. PMID- 1457912 TI - A skeletal muscle actuator for an artificial heart. AB - The authors developed a system to use skeletal muscle as an artificial heart actuator. This system consists of a flexible rod, sheath, crank, and cam to transmit the muscle power to a pusher plate pump and actuate it. The latissimus dorsi muscle was dissected at the lower ribs, and its end was connected with the flexible rod. The contraction of skeletal muscle was linearly transmitted, with the rod introduced inside the sheath, to the pump. The whole system was implanted in dogs (14-18 kg) and pump performance was evaluated with a mock circulatory system (preload = 10 mmHg, afterload = 75 mmHg). In these experiments, the pump output was maintained at 0.8 to 2.0 L/min (60 bpm) for 200 min, with a non preconditioned muscle that was stimulated continuously. The output obtained was 2.5 mW/gram. Efficiency of this system was about 50% of the muscle power available. When the muscle was stimulated intermittently every 30 min, pump flow was maintained at > 0.8 L/min for 20 hr. Advantages of this system are: 1) the muscle power was linearly transmitted effectively, 2) this system could be installed with minimal surgery and without interruption in blood flow to the muscle, 3) the muscle is free from high intraventricular pressure that caused ischemia and, 4) the muscle can be set to the proper length in diastole to potentiate strong contractions. PMID- 1457913 TI - Improved patency of an elastomeric vascular graft by hybridization. AB - A newly devised hybrid graft with high antithrombogenicity for small caliber vascular grafts was developed. The design concept was based on the incorporation of a compliant open cell structured graft, autogenous endothelial cells (ECs), and artificial basement membrane. The latter, a gel complex of type I collagen and dermatan sulfate that showed enhanced adhesion and growth of ECs but reduced platelet adhesion, was coated onto a microporous polyurethane graft (internal diameter, 3 mm; length, 4.5 cm), with near-natural compliance. Ten seeded grafts were implanted bilaterally into the carotid arteries of dogs; anticoagulant or antiplatelet therapy was not administered. This hybrid graft showed a marked improvement in patency at 1 month compared with that of simply preclotted grafts (control specimens). This result was explained by the almost complete endothelialization when the graft was implanted, a high degree of adherent strength resistance to shear stress, and a high proliferative potential. Thus, this approach of combining biomechanical and cellular engineering designs may lead to an important functional small caliber graft. PMID- 1457914 TI - Growth and functional assessment of pulmonary valves in pigs after replacement of sinuses of Valsalva. AB - Neopulmonary artery stenosis may occur after the arterial switching procedure to correct transposition of the great arteries. One technique to reduce this complication is to use a single rectangular piece of autogenous pericardium to reconstruct two adjacent sinuses of Valsalva and maintain pulmonary artery size. The long-term effect of this technique on pulmonary artery and valve growth and function is unknown. To assess this technique, Yorkshire-cross pigs (n = 5) weighing 29 +/- 1.7 kg (mean +/- SEM) were anesthetized, and during cardiopulmonary bypass, the pulmonary artery was transected distal to the pulmonary valve. Pulmonary artery diameter and commissure distances were measured. Two adjacent pulmonary artery sinuses of Valsalva were completely excised from the anulus to 4 mm distal to the commissures, leaving 2 mm of pulmonary artery tissue attached to the skeletonized commissure and on each side of the one remaining intact sinus of Valsalva. A single rectangular patch of fresh autologous pericardium was sutured to the anulus and remnant of the pulmonary artery along the commissure and edges of the one intact sinus of Valsalva. Pericardium composed two thirds of the circumference of the proximal pulmonary artery; this was anastomosed to the distal pulmonary artery. Weight gain occurred at a rate of 0.6 kg/day (median). The animals underwent right heart catheterization and cineangiography. They were killed 157.2 +/- 12.9 days post operatively. The reconstructed pulmonary artery grew from 17.6 +/- 0.8 mm to 30.8 +/- 1.5 mm (p < 0.01), and the commissure distances grew from 17.0 +/- 1 mm to 27.2 +/- 1.6 mm (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457915 TI - Venous access pressures and the detection of intra-access stenosis. AB - Venous pressure measured by the dialyzer is an unreliable measure of intra-access venous pressure. During dialysis and zero extracorporeal blood flow, intra-access venous limb pressure (VPd) was measured directly 401 times in 133 subjects using a high flow "in-line" three-way stopcock adjacent to the venous return needle. Subjects with systolic VPd/systolic blood pressure (BP) > or = 0.4, inadequate blood flow, or edema in the access extremity were referred for angiography. Percent diameter lumen reduction by a stenosis (%D) > 50% was considered hemodynamically significant. The authors did 138 angiograms. It was found that VPd/BP increased with %D in both ePTFE bridge grafts and native fistulae. Measurements of venous limb VP/BP taken at the time of dialysis and at the time of angiography did not differ (n = 55). On 80 occasions, accesses had significant stenoses. The overall sensitivity of VPd/BP in ePTFE bridge grafts was 91% and specificity 91%. False negative results occurred in seven of 24 native and eight of 114 ePTFE graft studies; 14 of 15 patients had arm swelling caused by central stenosis. Recirculation > 15% was more sensitive (71%) in detecting stenosis in native accesses than was intra-access pressure. It was concluded that VPd/BP > 0.4 is a useful, sensitive, and specific criteria for detecting synthetic bridge graft accesses at risk for thrombosis. PMID- 1457916 TI - The effect of Doppler flow screening studies and elective revisions on dialysis access failure. AB - A retrospective study was undertaken to see if screening ultrasounds and elective surgical revision could decrease access failure. Two hundred fifty-three accesses [177 gortex grafts, 76 arteriovenous (AV) fistulas] were studied with duplex imaging. Patients were subdivided by access type, flow, percent stenosis, and whether they were surgically revised. Data was examined to determine access failure within 6 months. Ten of 76 fistulas clotted (13.1%), while 53 of 177 grafts clotted (29.9%) (p = 0.005). In Gortex grafts, stenosis (p < 0.05) and decreased flow (p = 0.005) correlated with clotting. In unrevised grafts with flow < or = 801 ml/min, 13 of 14 (92.8%) clotted, whereas of those with flow > or = 1603 ml/min only, 10 of 38 (26.3%) clotted (chi-square = 24.74; p < 0.0001). Only 1 of 18 (5.6%) revised grafts with flow < or = 1300 ml/min clotted, while 29 of 69 (42%) unrevised grafts clotted (p = 0.004). We were unable to demonstrate decreased clotting in fistulae with revisions. In conclusion, screening duplex scanning was able to select groups with a higher risk of access failure over the subsequent 6 months. Elective revision with correction of areas of stenosis in grafts with flows < or = 1300 ml/min significantly decreased the incidence of clotting. PMID- 1457917 TI - Vascular access thrombosis during recombinant human erythropoietin therapy. AB - The increased incidence of vascular access thrombosis (VAT) associated with recombinant human erythropoietin (r-HuEPO) therapy is multifactorial and controversial. Sixty-three hemodialysis patients who received > or = 12 weeks of r-HuEPO therapy were prospectively followed for the incidence of VAT. Those who experienced VAT (Group 1) were compared with those who did not (Group 2). The patients initially received r-HuEPO 50 U/kg intravenously three times a week. The dose was adjusted for a target hematocrit (t-Hct) of 30-33%. Twenty-five of the 63 patients (40%) experienced VAT (Group 1). These patients were older (mean, 54.0 +/- 14.0 years versus 47.3 +/- 15.0 years, p = 0.08). There was no difference between Groups 1 and 2 with respect to the baseline Hct level (21.5 +/ 2.9% versus 21.4 +/- 4.3%), the number of patients who achieved t-Hct (20 versus 28), and the mean time to reach t-Hct (18.6 +/- 15.1 weeks versus 16.9 +/- 16.2 weeks). However, 20 of 25 Group 1 patients (80%) were diabetic compared with only 18 of 38 Group 2 patients (47%, p = 0.0169, by Fisher's exact test). In addition, the types of vascular access differed markedly between the two groups: arteriovenous (AV) grafts/AV fistulae/Permcaths, Group 1: 21/3/1 versus Group 2: 15/21/2, p = 0.0018. It was concluded that the occurrence of VAT in r-HuEPO treated patients was not related to the patient's hematologic response to the drug, but rather, it depended upon the integrity of the patient's vasculature and the type of vascular access used. PMID- 1457918 TI - Effect of shear rates on protein adsorption in the total artificial heart. AB - Plasma protein adsorption is the first event in blood-material interaction and influences subsequent platelet adhesion and thrombus formation. Thromboembolic events are strongly influenced by surface characteristics of materials and fluid dynamics inside the blood pump. In vitro flow visualization, and an animal experiment with a moving actuator total artificial heart (TAH), were performed to investigate fluid dynamic effects on protein adsorption. The different levels of shear rate inside the ventricle were determined by considering the direction of opening of the four heart valves in the implanted TAH, and the visualized flow patterns as well. Each ventricle of the explanted TAH was cut into 12 segments according to the shear rate level. The adsorbed protein on each segment was quantified using an ELISA method after soaking in 2% (w/v) SDS/PBS for 2 days. Adsorbed protein layer thicknesses were measured by the immunogold method under transmission electron microscopy. Scanning electron microscopic observation showed that the right ventricle, immobilized with albumin, displayed different degrees of platelet adhesion on each segment, whereas the left ventricle, coated with polythyleneoxide-sulfonate, indicated nearly the same platelet adhesion behavior, regardless of shear rates. The surface concentrations of adsorbed proteins in the low shear rate region are higher than those in the high shear region, which was confirmed statistically. PMID- 1457919 TI - Changes with respect to time in the in vivo adsorption of plasma proteins onto artificial heart blood pumps. AB - The distribution of adsorbed plasma proteins (albumin, IgG, and fibrinogen) on 10 artificial heart blood pumps coated with 2 segmented polyurethanes was evaluated quantitatively after long-term in vivo experiments with goats to determine how the adsorption of plasma proteins on the pumps was affected by the kinds of biomaterials used, and by the pumping duration. The adsorbed plasma proteins on the materials were determined quantitatively using the iodine-125 conjugated antibody method. Microscopically, the adsorbed plasma proteins were marked by the gold colloid conjugated antibody method, and analyzed using a field emission scanning electron microscope. The macroscopic results showed that: 1) the adsorbed plasma proteins on KP-13 were more evenly and finely distributed than those on Cardiothane; 2) with KP-13, the adsorption of IgG and albumin at the center of the pumps was significantly less than in the peripheral areas, and the adsorbed IgG and albumin decreased significantly as the pumping duration increased; 3) in contrast, the adsorbed fibrinogen increased significantly with time; and 4) with Cardiothane, the tendencies for adsorbed IgG and albumin to decrease, and for adsorbed fibrinogen to increase, were less significant than with KP-13. Microscopically, the gold colloids marking plasma proteins were found to not cover the whole of the surface, but were found scattered randomly or in clusters, with no relationship observed between the distributions of the three plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457920 TI - Performance of a hydrogel composite pericardial substitute after long-term implant studies. AB - A novel composite patch has been tested as a pericardial substitute to reduce adhesion formation after cardiac surgery. The patch consists of poly 2 hydroxyethyl methacrylate (pHEMA) hydrogel reinforced with a polyethylene terephthalate (PET) mesh. The hydrogel-PET composite pericardial patches were implanted in canines for 6, 9, and 12 months. Upon termination, adhesion formation and epicardial reaction to the implant were rated. No adhesions formed between the patch and the native pericardium or epicardium. A thin fibrous layer on the epicardium progressively developed where the patch contacted the heart. The coronary anatomy remained visible. Histologically, the response to the implant was fibrous in nature. No significant signs of cellular inflammation were found. The gross appearance of the retrieved patches was nearly identical to that of preimplant patches. Mechanical tests showed no significant changes (alpha = 0.05) in patch strength or stiffness. Hydrogel water content initially increased during implantation. The thickness of the patch did not change significantly (alpha = 0.05) throughout the study. Scanning electron microscopy (SEM) revealed unequal layers of hydrogel on either side of the PET mesh and cracks in the hydrogel surfaces of retrieved patches. Both SEM and light microscopic observation of the patches showed traces of calcification in patches in the 9 and 12 month studies. PMID- 1457921 TI - Heparin-free hemodialysis with an oral anti-platelet agent. AB - Heparin-resistant blood clotting in hemodialysis, caused mainly by platelets activated with artificial materials, was ameliorated by oral administration of a newly developed anti-platelet agent, 4-cyano-5,5-bis (4-methoxy phenyl)-4 pentenoic acid (E5510, Eisai Co. Ltd., Tokyo, Japan). Six hemodialysis patients, who were given 0.5. 1, 2, and 4 mg of E5510 orally 1 to 2 hr before starting hemodialysis, underwent hemodialysis using a hollow fiber dialyzer (PMMA or cellulose acetate). The platelet aggregation rate was depressed according to dose response, and fell to less than 30% of the initial value with 2 mg of E5510. Plasma thromboxane B2 concentration was depressed significantly. Bleeding time was mildly but not significantly prolonged. Based on these results, we tried heparin-free hemodialysis using E5510 as sole anticoagulant. Six of nine patients were successfully hemodialyzed with minimal blood clotting in the dialyzer and drip chambers. Three patients needed additional low dose heparin to prevent blood clotting in the circuit's air trap. Neither hemorrhagic complications nor other side effects were observed in these cases. E5510 is considered to be a promising oral anti-thrombogenic agent for patients with heparin-resistant blood clotting or heparin-free hemodialysis. PMID- 1457922 TI - Study of anatomic constraints using three dimensionally reconstructed images for total artificial heart implantation. AB - The authors established a method of clarifying the three dimensional interrelationship among the mitral and tricuspid annuli, ascending aorta, main pulmonary artery, diaphragmatic surface of the heart (DS), and anterior thoracic wall, using four chamber view magnetic resonance imaging. This method was applied to measuring the parameters that restrict the size and shape of a total artificial heart (TAH) from three dimensional reconstructed images of six normal subjects. Assuming that the TAH is implanted on the diaphragm, which corresponds to DS, the width of the TAH is restricted to 7.6 cm, the transverse dimension of the cardiac base (D-B), and the height to 7.8 cm, the dimension from the DS to the center of the pulmonic annulus (DS-P1). Depth is restricted by the longitudinal dimension of the left ventricle projected on the DS (D-L). While D-L in early systole is 9.7 mm, in late systole D-L is reduced to 7.6 cm. The angle (DS) (AW) is 65.7 degrees; this is the angle between the DS and anterior thoracic wall that restricts the shape of the TAH. While these data in normal subjects may be useful for TAH implantation, in the patient with acute cardiac failure, further study of patients with chronic cardiac failure is necessary. PMID- 1457923 TI - Permeation of silicone oil through a diaphragm in an electrohydraulic ventricular assist system. AB - This study was designed to investigate the permeation of silicone oil through a pump diaphragm made of Pellethane in the authors' electrohydraulic ventricular assist system (EHVAS) and to evaluate influences on organ function. The permeability of the diaphragm to silicone oil was investigated by in vitro experiments. Influences on organ function were evaluated in five goats with an EHVAS by monitoring serum silicon levels (SSi), blood chemical parameters, and histologic findings. Elevation of silicone oil levels in Pellethane sheets immersed in silicone oil demonstrated that the Pellethane diaphragm was, in fact, permeable to silicone oil. The permeation rate of silicone oil was calculated to be 1.75 ml/year in the authors' EHVAS from the data of a diffusion apparatus test. Serum silicon levels did not increase during the EHVAS pumping, and renal and hepatic function were not affected. No abnormality or deposit suggestive of silicone oil was observed. However, the problem of permeation of silicone oil through the pump diaphragm must be solved to allow for a circulatory assist device for long-term use. PMID- 1457924 TI - Heparin induced thrombocytopenia in patients undergoing intra-aortic balloon pumping after open heart surgery. AB - Heparin is usually administered to patients with intra-aortic balloon pumps (IABP) to prevent thromboembolism. In addition to thrombocytopenia caused by IABP mechanical damage to platelets, exposure to heparin can cause heparin induced thrombocytopenia (HIT). Heparin induced thrombocytopenia is caused by an immune mechanism in which heparin antibodies are produced, causing platelet aggregation, leading to bleeding or thromboembolic complications. Over a 9 year period, 35 of 764 (4.5%) patients with IABPs have been diagnosed as having HIT. Surgical procedures included coronary artery bypass (CABG) in 14 (40%), valve repair or replacement in 7 (20%), and CABG and other cardiac procedure in 14 (40%). Lowest platelet counts ranged from 17,000-114,000/mm3 (median, 44,000/mm3). Thirty-three of 35 (94.3%) had mediastinal hemorrhage requiring infusion of multiple blood products, and 6 of these 35 (17%) required return to the operating room. Seventeen of 35 (48.6%) experienced thromboembolic complications. Hospital mortality was 15 of 35 (42%). Etiology of thrombocytopenia in patients on IABPs is multifactorial. Patients on an IABP who develop thrombocytopenia should be tested for heparin dependent anti-platelet antibodies to rule out HIT. When a heparin antibody is present, heparin must be discontinued and alternate forms of anticoagulation/platelet inhibition initiated to reduce morbidity and mortality. PMID- 1457925 TI - Influence of an impeller centrifugal pump on blood components in chronic animal experiments. AB - A chronic animal experiment was designed to examine the changes in blood components induced by the use of a centrifugal pump (CP). In the pump, an impeller spins in a blood chamber by magnetic coupling with a rotating magnet outside the blood chamber. A pulsatile ventricular assist device was implanted between the left atrium and the descending aorta in four goats weighing from 63 to 75 kg; the CP was installed to replace the assist device, without surgery and anesthesia, more than 2 weeks later when the influences of implantation surgery were diminished. Antithrombotic therapy was performed with oral administration of an antiplatelet agent, cilostazol, a cyclic adenosine monophosphate phosphodiesterase at a dose of 30 mg/kg/day. No significant differences were observed in any of the following parameters: 1) hematocrit, 2) plasma free hemoglobin, 3) lactic acid dehydrogenase, 4) adenosine diphosphate, 5) platelet count, 6) fibrinogen, and 7) antithrombin III, between the data before and after the use of the CP, nor were deformation or pseudopods of platelets seen. The CP developed in the authors' institute and evaluated in this study did not damage blood components, and it proved to be a promising device for long-term use. PMID- 1457926 TI - Characteristics of artificial red cells. Hemoglobin encapsulated in poly-lipid vesicles. AB - Artificial red cells (ARC) were prepared by encapsulation of purified human Hb with polymerizable phospholipid, 1,2-bis (2,4-octadecadienoyl)-sn-glycero-3 phosphocholine (DODPC). The polymerized lipid bilayer of the ARC produced great physical stability that could not be achieved using a non-polymerizable lipid for encapsulation. ARC showed no change in particle size or distribution or leakage of Hb after repeated freeze thawing (stability test). ARC have also been studied with regard to biocompatibility. The authors' results showed low acute toxicity (> 8000 mg/kg) and adequate blood compatibility. The result of transfusion tests in dogs showed that ARC had sufficient oxygen transporting capabilities. PMID- 1457927 TI - Peritoneal dialysis solution calcium concentration regulates peritoneal fibroblast proliferation in CAPD. AB - Peritoneal fibrosis remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis (CAPD), by reducing ultrafiltration capacity. Since studies in vitro have shown that cytoplasmic Ca2+ regulates the proliferation of most cell lines and the release of cytokines from immune cells, eight uremics and four controls at the start of CAPD were evaluated for the in vitro effects of different peritoneal dialysis solution (PDS) Ca2+ concentrations (1, 1.25, 1.75, and 2 mmol/L) on: 1) peritoneal fibroblast (PF) proliferation; 2) peritoneal macrophage (PM) and peritoneal lymphocyte (PL) release of interleukin 1 (IL-1) and interferon-gamma (IFN-gamma)--cytokines that are known to induce PF proliferation; and 3) cytoplasmic Ca2+ concentrations in PF, PM, and PL. Results showed that in both the uremics and controls, increasing the dose of Ca2+ in the medium induced a dose-dependent rise in PF proliferation, and in the release of IL-1 and IFN-gamma from PM and PL. Meanwhile, the cytoplasmic Ca2+ concentration of PF, PM, and PL also increased. With a PDS containing 1 mmol/L of Ca2+ in the uremics, these parameters were below normal; they exceeded the norm with a Ca2+ concentration of 1.75 and 2 mmol/L, and were normal with a Ca2+ concentration of 1.25 mmol/L. These data suggest that in CAPD patients, the use of a low Ca2+ PDS (1 and 1.25 mmol/L) may be useful in reducing the proliferation of PF and the production of IL-1 and IFN-gamma from PM and PL, thereby preventing peritoneal sclerosis. PMID- 1457928 TI - Factors influencing transperitoneal calcium balance during CAPD. AB - A dialysate containing a calcium concentration of 1.75 mmol/L has been the standard in CAPD for a long time. This concentration was chosen to achieve a positive calcium balance to suppress hyperparathyroidism. In the measurement of peritoneal calcium mass transfer, conflicting results have been published, with positive and negative calcium balances reported. These differences have been explained by differences in the filtration rate, and a negative correlation between the filtration rate and the peritoneal calcium mass transfer can be found. Whereas nearly all patients in this study had a negative calcium balance using a glucose solution of 3.86%, a wide variation was found for the 1.36% glucose solution. There were several patients who had a positive calcium balance despite a positive filtration rate. The explanation for this finding lay in differences in serum concentrations of calcium, and especially differences in the size of the total exchangeable calcium pool that contains the plasma calcium compartment. A negative correlation between peritoneal calcium balance and the size of the total exchangeable calcium pool could be demonstrated. This finding may explain the differences in the peritoneal calcium flux reported in the literature. As an enlargement of the exchangeable calcium pool correlates with the progression of vascular calcification, therapeutic efforts should be directed toward prevention of an enlargement of this pool. PMID- 1457929 TI - Low calcium peritoneal dialysis solution. Effects on calcium metabolism and bone disease in CAPD patients. AB - Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (AI) intake. By maintaining high serum Ca2+ levels, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. To evaluate the effects of a low Ca2+ peritoneal dialysis solution (PDS; 1.25 mmol/L) on calcium metabolism, the following were studied in continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (six with high PTH levels, and high turnover bone disease [Group 1], and six with low PTH levels, and low turnover bone disease [Group 2] documented by bone biopsies): 1) serum Ca2+ and PO4 levels; 2) serum PTH levels; 3) serum AI levels; and 4) bone morphology. The follow-up was 12 months. In both groups, within the third month, there was a decrease in serum Ca2+. In Group 2, serum PTH increased, reaching the norm, and in Group 1 it further increased, exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to give oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels while stopping AI gels. This did not induce any increase in serum Ca2+, whereas serum AI fell significantly. In Group 1, to avoid a further rise of serum PTH, the low Ca2+ PDS was supplemented with calcitriol (mean 3.5 +/- 0.5 microgram/day); this was followed by a reduction in serum PTH with no increase in serum Ca2+ or PO4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457930 TI - Experimental Staphylococcus epidermidis implant infection in the mouse. Kinetics of rifampin and vancomycin action. AB - Staphylococcus epidermidis implant infections remain a therapeutic challenge; they frequently result in failure of conservative management and require removal of the implant. This resistance to antibiotic therapy has been ascribed to the presence of a protective bacterial biofilm at the surface of the implant. An animal model of implant associated infection has been developed in which preformed bacterial biofilm catheter segments are implanted intraperitoneally, resulting in a chronic standardized localized infection. The authors have determined the superior rapid action of rifampin (Cieba-Geigy) compared to vancomycin hydrochloride (Eli Lilly) and determined that the combination is superior to either used alone. No rifampin resistant surviving infection was noted, which indicates the significant contribution of mammalian host defenses. This animal model is an excellent vehicle for the study of Staphylococcus epidermidis implant associated infection and the evaluation of the relative efficacy of antibiotic regimens, singly and in combination. PMID- 1457931 TI - Pivot design in bileaflet valves. AB - The design criteria leading to the development of a new bileaflet valve (Sorin Bicarbon) were derived from the analysis of functional requirements, the performance of existing prostheses, and the availability of an advanced carbon coating technology (Carbofilm). The hinge is the critical element affecting fluid dynamics, durability, and thrombus formation in bileaflet valves. A comparative study of three existing models led to a new hinge design that was based on coupling two spheric surfaces with different radii of curvature (leaflet pivot and hinge recess) and obtained by electroerosion into a Carbofilm-coated metallic housing. In this valve, the point of contact moves continuously by rolling, not sliding. This minimizes friction and wear and allows uninterrupted washing of the blood exposed surfaces even during diastole (a finding established in patients using transesophageal echocardiography). Tricuspid implantation without anticoagulation in 33 sheep did not lead to thrombotic events (follow-up, 40-400 days). In the first 36 clinical implants observed for 15 months (mitral position, size 29; two unrelated deaths), the mean diastolic gradient by echo Doppler was 4 +/- 1.25 mmHg; the functional area was 3.2 +/- 0.6 cm2. No leaflet fracture and no thrombotic or embolic complications were observed clinically using a standard anticoagulant regimen. PMID- 1457932 TI - A non-conventional reniform heart valve bioprosthesis with improved performance. AB - Conventional bioprosthetic heart valves have been designed with circular mounting rings. This article describes a mitral bioprosthetic valve consisting of three bovine pericardial leaflets with a "reniform" base. Its shape resembles that of the mitral anulus, and therefore, it provides a better anatomic fit. Hydrodynamic comparisons were made between conventional valves (CV) and equivalent sized reniform valves (ERV) that would adapt to the same anulus. Under steady flow of 30 L/min, pressure drops were compared in CVs and ERVs. For CV sizes 27, 29, and 31mm, the ratios of pressure drops compared with ERVs were 2, 1.49, and 1.30, respectively. With the same flow rate, the ratios of effective orifice areas (EOA) for CVs and ERVs in sizes 27, 29, and 31mm were 1.41, 1.21, and 1.14, respectively. Under pulsatile flow (mean flow, 5 L/min, 100 beats/min [bpm]), the pressure drop across CVs was averaged for sizes 27, 29, and 31mm, and found to be 1.51-fold the averaged pressure drops for ERVs. In addition, ERV sizes 27, 29, and 31mm had EOAs averaging 1.24-fold those of CVs. Similarly, for an 80 bpm frequency, the pressure drops across CVs for the three sizes averaged 1.48-fold that of ERVs. The EOAs of ERVs were 1.22-fold those of CVs averaged for the three sizes. PMID- 1457933 TI - Assessment of the in vitro transport parameters for ethanehydroxy diphosphonate through a polyurethane membrane. A potential refillable reservoir drug delivery device. AB - Calcification (CALC) is the most frequent cause of failure in bioprosthetic heart valves (BHV) fabricated from glutaraldehyde pretreated porcine aortic valve or bovine pericardium. Site specific controlled administration of ethanehydroxy diphosphonate (EHDP), using numerous carriers, has been successful in inhibiting CALC of BHV tissue in an accelerated rat subdermal model, without adverse effects on serum calcium, bone development, or overall somatic growth. The current study was designed to evaluate refillable reservoir devices fabricated from polyurethane (Biomer Woburn, MA) with regard to their transport properties relative to EHDP. The refillable reservoirs were evaluated for EHDP release in vitro at 22 degrees C (under perfect sink conditions) into both a physiologic receptor phase (N-2 hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer, pH = 7.4) with (1.5 mM) or without Ca2+ present. Transport parameters for EHDP diffusion through the polyurethane membranes used to fabricate the reservoirs were significantly different for the two receptor phases evaluated. The mean diffusion coefficients (D) for EHDP through the polyurethane membrane into each receptor phase were not significantly different. However, an approximately 3.5 fold reduction was observed in the mean value of the partition coefficient (K) for EHDP when EHDP was evaluated for release into a receptor phase that contained 1.5 mM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457934 TI - Initial clinical trial of a closed loop, fully automatic intra-aortic balloon pump. AB - A new generation, closed loop, fully automatic intraaortic balloon pump (CL-IABP) system continuously optimizes diastolic augmentation by adjusting balloon pump parameters beat by beat without operator intervention. In dogs in sinus rhythm and with experimentally induced arrhythmias, the new CL-IABP system provided safe, effective augmentation. To investigate the system's suitability for clinical use, 10 patients meeting standard indications for IABP were studied. The patients were pumped by the fully automatic IABP system for an average of 20 hr (range, 1-48 hr). At start-up, the system optimized pumping parameters within 7 20 sec. Evaluation of 186 recordings made at hourly intervals showed that inflation began within 20 msec of the dicrotic notch 99% of the time. In 100% of the recordings, deflation straddled the first half of ventricular ejection. Peak pressure across the balloon membrane averaged 55 mmHg and, in no case, exceeded 100 mmHg. Examination of the data showed that as soon as the system was actuated it provided consistently beneficial diastolic augmentation without any further operator intervention. Eight patients improved and two died (one of irreversible cardiogenic shock and one of ischemic cardiomyopathy). No complications were attributable to the investigational aspects of the system. A fully automated IABP is feasible in the clinical setting, and it may have advantages relative to current generation IABP systems. PMID- 1457935 TI - Clinical responses to ventricular assistance versus transplantation in a series of bridge to transplant patients. AB - Hemodynamic and peripheral organ responses to ventricular assistance were compared with transplantation in a cohort of patients bridged with the HeartMate 1000 IP left ventricular assist device (LVAD) (Thermo Cardiosystems Inc., Woburn, MA). The study population included 27 patients that were supported an average of 102 days (range, 15-324 days). Two hepatic (total bilirubin and serum glutamic oxaloacetic transaminase [SGOT]) and two renal (creatinine and blood urea nitrogen [BUN]) parameters were measured: 1) before LVAD insertion, 2) 30 and 60 days during ventricular assistance, 3) before transplantation while still on the VAD, and 4) 30 and 60 days after transplantation. Total bilirubin values were significantly greater just before LVAD implant (2.3 mg/dl) than before transplantation (0.7 mg/dl). Although there was no difference after 30 days of either treatment, the total bilirubin values were greater at 60 days after transplantation (1.1 mg/dl) than at an equivalent time on the LVAD (0.6 mg/dl). The SGOT values were also significantly reduced before transplantation. No differences at 30 and 60 days after either procedure were noticed. Creatinine and BUN values were greater before LVAD implant (1.7 and 37 mg/dl) than before transplantation (1.2 and 19 mg/dl). The creatinine values were also greater after transplantation at 30 and 60 days (2.0 and 1.6 mg/dl) than at comparable intervals after LVAD implantation (1.0 and 1.2 mg/dl), presumably as a result of the use of immunosuppressive drugs. End organ function was markedly improved while on the device, enhancing the physiologic status of the patients before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1457936 TI - Non-pulsatile circulatory support in 90 cases. AB - Survival after cardiac arrest is reportably less than 10%; after cardiogenic shock it is less than 50%; and in failure to wean post-cardiotomy (even with centrifugal pumps in several large series) it is only 11-21%. The authors' experience with non-pulsatile circulatory support in 90 consecutive cases from 1986-91 has shown improved survival. The emergent cardiopulmonary bypass system (CPS) was used in 67 of the 90 patients, with 65 patients resuscitated, 34 (51%) weaned, and 19 (28%) transferred to other cardiovascular support therapies. Of the patients weaned or transferred, 34 (51%) survived > 24 hr, and 21 (31%) survived > 30 days. In the current series, 108 major cardiovascular procedures were done during or after CPS implementation. An in-house trained nursing team working with surgeons and perfusionists contributed to early implementation of the CPS and the subsequent improved survival. The BioMedicus centrifugal pump (VAD) was used predominantly for post-cardiotomy failure to wean in 16 patients and as a bridge to transplant in 7 patients. Fourteen patients (61%) were weaned or transplanted. Of these 14 patients, 11 (48%) survived > 30 days. Non-pulsatile circulatory support devices are relatively inexpensive and available to most hospitals. With careful patient selection and early implementation, one can expect survival of 37% of patients who would otherwise not survive. PMID- 1457937 TI - An abdominally placed, implantable left ventricular assist system for long-term use. AB - An implantable left ventricular assist system was developed for long-term use. The system includes an implantable blood pump, a portable control drive unit (CDU), and a monitoring system. The blood pump was designed to be positioned in the left abdominal wall and was made of segmented polyether polyurethane. A percutaneous drive line connected it to the external CDU. The CDU included a continuous pump performance monitoring system that measured electrical impedance between the two metal connectors of a blood pump. In animal experiments using six adult goats, the pump was installed between the left ventricular apex and the descending aorta, and it was placed in the abdominal wall. No antithrombogenic agents were administered during the course of the experiment. This LVAS was easy to use and provided stable hemodynamic conditions for > 8 weeks. Pump output (Op), estimated by impedance, was linearly related to Op measured with an electromagnetic flowmeter. Pump performance was effectively estimated, and the fill-empty drive was well controlled by impedance. There were no significant abnormal hematologic or blood chemistry values, no signs of infection around the pump pocket (except in one animal), and no obvious thromboembolic symptoms. Maximum flow was 6.7 L/min with use of a prototype portable CDU (dimensions, 500 x 168 x 435 mm; weight, 16 kg). In conclusion, this LVAS is promising for long term clinical use. PMID- 1457938 TI - Thrombin activity resides on LVAD Dacron inflow and outflow grafts. AB - Patients on left ventricular assist devices (LVADs) are at increased risk for thromboembolism, and they experience elevations in platelet release and thrombin activity indices during device implantation. The Dacron grafts that lead from the ventricle to the LVAD and back to the aorta may harbor thrombin activity and protect this thrombin from anticoagulant action. To investigate this possibility, specimens isolated from LVAD grafts at the time of device explantation or implantation were incubated with citrated platelet poor plasma (cPPP), cPPP and 2 U/ml of heparin, cPPP and 2 U/ml of recombinant hirudin (r-hirudin), or cPPP and 50 U/ml of heparin. Thrombin activity was measured by the increase in incubated cPPP fibrinopeptide A (FPA) concentrations over cPPP FPA levels, without material contact. A chromogenic substrate for thrombin verified the effects seen. Thrombin activity was found at comparable levels on both the inflow and outflow LVAD grafts at explantation. This activity was not inhibited by low concentrations of heparin, but 50 U/ml of heparin and 2 U/ml of r-hirudin reduced the activity. At graft implantation (after preclotting), thrombin activity was higher than at explantation, but susceptibility to inhibition by heparin was also significantly greater. These results confirm that the LVAD Dacron grafts harbor surface thrombin activity resistant to anticoagulation that may be a primary source for LVAD thrombogenicity. PMID- 1457939 TI - Heparin immobilization by surface amplification. AB - A method to increase the amount and improve the bioactivity of heparin (HEP) immobilized on a polymer surface was developed. The surface of polyurethane-urea (PU) coated glass beads was first modified with diisocyanates, followed by surface grafting of polyfunctional polymers (PFP), including: poly(vinyl alcohol), poly(ethyleneimine), and poly(allylamine). The functional groups of the surface grafted PFP (-OH, -NH, or -NH2) were modified with diisocyanates (TDI) to amplify the surface concentration of isocyanate groups, alpha, omega-diamino terminated polyethylene oxide (PEO; molecular weight, 4,000 daltons) was then coupled to the surface grafted PFP, and the free amino groups were derivatized with TDI. Finally, HEP was coupled to the amplified surface through free -NCO groups of PU-PFP-PEO. The surfaces were quantified during each step of the procedures for -NCO groups and HEP. All grafted surfaces showed a four to eightfold increase in -NCO content and a twofold increase in immobilized HEP content compared with HEP immobilized directly onto the PU surface. The HEP bioactivity tests (including activated partial thromboplastin time, thrombin times, and factor Xa) demonstrated an increased bioactivity of HEP when immobilized through PFP-PEO compared with PFP and PU alone. PMID- 1457940 TI - Albumin immobilized polyurethane and its blood compatibility. AB - Surface pretreatment with albumin on a blood contacting material inhibits platelet adhesion, activation, and subsequent thrombus formation. Although adsorbed albumin improves blood compatibility, rapid desorption occurs when this surface is exposed to circulating blood. In this study, human serum albumin was immobilized on a polyurethane (PU) surface to investigate its blood compatibility and extended effects on a blood-material interface. The PU surface was treated with hexamethylene diisocyanate (HMDI), and the PU-HMDI was further grafted with albumin to produce an albumin immobilized PU surface (PU-albumin). The PU-albumin surface was characterized by attenuated total reflection infrared electron spectroscopy for chemical analysis, scanning electron microscopy, and dynamic contact angle. Blood compatibility was evaluated by in vitro protein adsorption, platelet adhesion, and occlusion time in an ex vivo rabbit arterio-arterial shunt. Immobilization of albumin was confirmed by the disappearance of the -NCO peak observed at 2,250 cm-1 on the PU-HMDI surface by infrared spectroscopy and the existence of sulfur atomic percent by electron spectroscopy for chemical analysis. The concentration of PU-albumin was approximately 5.8 micrograms/cm2. The PU-albumin also showed a slight increase in hydrophilicity on the Wilhelmy plate method, and there was less fibrinogen adsorption than a PU control. In addition, PU-albumin had less platelet adhesion, platelet activation, and thrombogenicity. The ex vivo occlusion time of untreated PU was 50 min, that of PU-albumin was extended to 150 min, indicating that a PU-albumin surface has better blood compatibility than PU alone. PMID- 1457941 TI - Binding kinetics of thrombin and antithrombin III with immobilized heparin using a spacer. AB - The immobilization of heparin onto polymeric surfaces using a hydrophilic spacer was effective in curtailing surface induced thrombus formation. In this study, the binding kinetics of immobilized heparin with antithrombin III (ATIII) and thrombin were investigated. Low molecular weight heparin (molecular weight, 6,000 daltons) was fractionated on an ATIII affinity column, and it was immobilized onto a styrene/p-amino styrene random co-polymer surface via hydrophilic spacer groups. This polymer substrate was coated onto glass beads (diameter range, 0.088 0.105 mm). PEO (molecular weight 3,400), modified by tolylene diisocyanate, was covalently coupled as a spacer group, followed by heparin. The bioactivity of immobilized heparin was approximately 16.2%, relative to free heparin, and nearly 1:1 binding between heparin and PEO was calculated. The binding constants of immobilized heparin and ATIII, and immobilized heparin and thrombin, were 0.958 x 10(7) M-1 and 1.76 x 10(8) M-1, respectively. The immobilized heparin bound with both ATIII and thrombin, and the binding mechanism was similar to that of free heparin. PMID- 1457942 TI - Acute renal failure in critical illness. Conventional dialysis versus acute continuous hemodiafiltration. AB - The dialytic therapy of choice in critically ill patients with acute renal failure (ARF) is a matter of controversy. The clinical outcome of such patients managed with either conventional dialytic therapy (CDT) or acute continuous hemodiafiltration (ACHD) was compared through retrospective review of medical records from the intensive care unit of a tertiary institution. Records from 167 critically ill patients with ARF consecutively treated in the same intensive care unit were reviewed. Eighty-four patients with ARF treated by CDT were compared to 83 treated with ACHD. The etiology of ARF and the degree of illness severity were similar in both groups (failing organs: CDT 3.9 vs. ACHD 4.1; mean APACHE II score: CDT 25.8 vs. ACHD 28.1). Overall survival was 29.8% for the CDT patients and 41% for the ACHD group (NS). In those with two to four failing organs, survival was greater in the ACHD group (53.8% vs. 31.1%; p < 0.025). This was also true for patients with an intermediate APACHE II score (24-29) who demonstrated better survival when treated by ACHD (46.4% vs. 12.5%; p < 0.025). Acute continuous hemodiafiltration was associated with better control of azotemia and hyperphosphatemia and increased nutritional intake. This retrospective study suggests that ACHD may offer clinically significant advantages over CDT, particularly in patients with an intermediate degree of critical illness severity. PMID- 1457943 TI - Intermittent venovenous hemofiltration as a chronic treatment for refractory and intractable heart failure. AB - Chronic heart failure (HF) is considered to be refractory when persisting despite an intensive drug regimen, or intractable when requiring "artificial" supports. Among them, hemofiltration (HE) has been used frequently, but only on an "acute" basis, to induce fast and safe water removal. Since 1985 the authors have treated refractory and intractable HF first by means of acute CAVH (continuous arteriovenous HE: 11 patients) and then (1988-1992) with IVVH (intermittent venovenous HE), initially done on an "acute" basis (13 patients) and then an a chronic basis (CIVVH): 8 subjects (6M, 2F; mean age, 60.8 years), 3 with RCHF and 5 with ICHF. This report deals with our experience in CIVVH. All patients were in severe failure. During a follow-up period of 63 months (range, 1-17/patient), 82 IVVH treatments (10.2/patient) were carried out, using this schedule: permanent Tesio catheter in superior vena cava, 0.6 m2 filter, double blood pump (blood flow = 80-250 ml/min); transmembrane pressure = 50-150 mmHg; mean ultrafiltration = 19 ml/min; replacement fluid = 8.6 ml/min; and session time = 340 +/- 88 min, according to individual dry weight (bioimpedance system). Six patients died (1-13 months after IVVH began); four of six had ICHF and two of six had RCHF; five of eight patients showed a significant amelioration of functional state, changing from fourth to third, to second and first degree failure, but this was after heart transplantation. In all cases a marked reduction in the drug regimen and in hospitalization was the rule. PMID- 1457944 TI - Urea kinetics during continuous hemofiltration. AB - Urea kinetic analysis allows for the calculation of the urea distribution volume and urea generation rate. This method was employed in patients with acute renal failure managed by continuous venovenous hemofiltration (CVVH). Based on serial serum urea nitrogen concentration measurements, each patient's treatment course consisted of both steady state and non-steady state periods. Thirteen data sets were obtained from 11 critically ill patients treated with CVVH. The duration of therapy was 9.5 +/- 7.5 days (mean +/- SD). Serum urea nitrogen concentration fell from 114 +/- 32 mg/dl to a steady state value of 79 +/- 17 mg/dl (p < 0.0005). The urea distribution volume was 0.55 +/- 0.11 L/kg (range 0.29-0.73), and the urea generation rate 11.7 +/- 3.1 mg urea N/min (range 7.1-17.3). The steady state serum urea nitrogen concentration had a linear relationship to the rate of urea generation (r = 0.92). Urea kinetic analysis permitted the simultaneous determination of the urea generation rate and distribution volume, on an individualized basis, in patients with acute renal failure treated with CVVH. PMID- 1457945 TI - Peritoneal membrane plasmapheresis. AB - A novel process has been devised that uses the peritoneal membrane to remove plasma proteins from the body at a rate comparable to conventional extracorporeal plasma-pheresis. A vasodilator (4 mg histamine phosphate) is added to 1 liter of hypertonic solution (485 mOsmol/L), and infused intraperitoneally with a residence time of 4 hr. Plasma containing proteins is convected across the peritoneum through open pores into the cavity and removed. The next alternating infusion is with a hypotonic solution (214 mOsml/L) containing a vasoconstrictor (1.0 mg norepinephrine). This infusion restores the fluid removed from the subject in the previous exchange, and prevents the rapid fall-off in protein removal rates obtained with repeated infusions with vasodilators only. Peritoneal membrane plasmapheresis was successfully tested on canines, with protein removal rates of between 30% and 50% of total serum protein per day for 13 days over a 22 day period. Peritoneal membrane plasmapheresis represents a potentially inexpensive, continuous/nightly home treatment for protein mediated diseases treatable by extracorporeal plasmapheresis. PMID- 1457946 TI - Prolongation of cardiac xenograft survival by double filtration plasmapheresis and ex vivo immunoadsorption. AB - A double filtration plasmapheresis (DFPP) technique and ex vivo immunoadsorption were applied to remove natural antibodies and avoid hyperacute rejection in discordant xenotransplantation. A swine heart was heterotopically transplanted into a dog's neck after DFPP and ex vivo immunoadsorption using a swine spleen or liver. Mean graft survival time was prolonged to 240 +/- 141 min in the group treated by combined DFPP and splenic adsorption, and 225 +/- 62 min in the group treated by combined DFPP and hepatic adsorption, whereas it was 9 +/- 5 min in the group without any treatment (p < 0.01). Mean removal rates of IgG and IgM were 85.5% and 93.3%, respectively. Anti-swine lymphocytotoxic antibodies and hemagglutination antibodies were also effectively removed. Deposits of canine IgM and C3 on the vascular endothelium of the graft were observed on immunofluorescence, which suggested that natural antibodies in the IgM fraction played an important role in xenohyperacute rejection. PMID- 1457947 TI - Differential regional function of the right ventricle during the use of a left ventricular assist device. AB - The use of a left ventricular assist device (LVAD) as a bridge to transplant is associated with a 52% incidence of RV failure requiring additional inotropic or mechanical support (RVAD). This study evaluated the differential performance of the RV free wall and septum to identify the need for additional RV support. Cross sectional views of the RV were obtained immediately before, and 1 hr after, Novacor LVAS implantation in 12 consecutive patients using transesophageal echocardiography. Each image was divided into a free wall portion (FW) and a septal portion (SP) by grids drawn from the center of gravity of the end diastolic endocardial outline to the junction between the FW and the SP. Percentage change between preimplant and postimplant for RV ejection fraction (RVEF), fractional area change for the FW (FAC-FW) and the SP (FAC-SP), and fractional shortening of the FW to SP distance (F-S) is reported for patients based upon the need for RV support: minimal (Group 1), maximal (Group 2). After LVAS implantation, patients showed a reduction in SP fractional area change. However, this reduction was most pronounced in Group 2. The degree of SP impairment may explain the mechanism of RV failure in patients on an LVAD. PMID- 1457948 TI - A miniature intraventricular axial flow blood pump that is introduced through the left ventricular apex. AB - A new intraventricular axial flow blood pump has been designed and developed as an implantable left ventricular assist device (LVAD). The pump consists of a tube housing (10 cm in length and 14 mm in diameter), a three-vane impeller combined with a guide vane, and a DC motor. This pump is introduced into the LV cavity through the LV apex, and the outlet cannula is passed antegrade across the aortic valve. Blood is withdrawn from the LV through the inlet ports at the pump base, and discharged into the ascending aorta. A pump flow of > 8 L/min was obtained against 90 mmHg differential pressure in the mock circulatory system. In an acute dog model, this pump could produce a sufficient output of 200 ml/kg/min. In addition, the pump flow profile demonstrated a pulsatile pattern, although the rotation speed was fixed. This is mainly due to the changes in flow rate during a cardiac cycle--that is, during systole, the flow rate increases to the maximum, while the differential pressure between the LV and the aorta decreases to the minimum. Thus, this simple and compact axial flow blood pump can be a potential LVAD, with prompt accessibility and need for less invasive surgical procedures. PMID- 1457949 TI - Thermal, operational, and storage stability of immobilized carbonic anhydrase in membrane lungs. AB - The significant improvement in CO2 removal rates from blood through membrane lungs with EMCO and ECCO2R is achievable by means of the immobilization of carbonic anhydrase (CA) onto the membrane surface. The practical application of this technology requires that the enzyme be maintained for long periods without loss of activity. Thus, studies were performed to evaluate the thermal, operational, and storage stability of CA in a cellulose nitrate-encapsulated, silicone rubber membrane-immobilized form. Cellulose nitrate microcapsules containing 1000 micrograms/ml CA were prepared using a modified version of the method of Chang, and immobilized onto a 0.06 m2 section of commercial silicone rubber membrane material. The extent of enzyme activity in free solution and in the encapsulated form was determined after long-term storage at 4 degrees C, 37 degrees C, and 50 degrees C. Likewise, in an in vitro test circuit, CO2 removal efficiency in both CA treated and untreated membrane lungs was measured for extended time periods of 10 hr over a 10 day period. The thermal stability tests showed a significantly greater degree of retained enzyme activity in the encapsulated form, over the free enzyme in solution, at all temperatures. This was especially evident at higher temperatures and when the enzyme was stored for extended periods. In the operational stability tests, the CO2 removal efficiency of the treated membrane was not degraded, and stayed significantly higher than the untreated membrane for extended time periods. This further illustrates the potential for the use of the immobilized enzyme, carbonic anhydrase, for improved CO2 removal efficiency. PMID- 1457950 TI - Autopsy findings in patients on postcardiotomy centrifugal ventricular assist. AB - Reported experience with ventricular assist devices (VAD) routinely includes the rate of thromboembolic events, which is commonly calculated from clinically evident findings. Fifty-four patients have had postcardiotomy circulatory support with the Sarns centrifugal device at our institution. We have reviewed 43 patients who failed to survive VAD support to compare the thromboembolism rate diagnosed clinically to that determined at autopsy. In the 35 patients who had no autopsy, there was one clinically apparent thromboembolic event (2.3%). In eight similar patients who had autopsy, there was no clinically apparent thromboembolism. Five of these eight patients (63%) had acute thromboembolic infarcts determined at autopsy. Three had evidence of pulmonary thromboembolism, two cerebrovascular infarction, two liver infarcts, two splenic infarcts, two kidney infarcts, and one each gastric, pancreatic, prostate, adrenal, cervical, and ileal infarcts. All had left and/or right ventricular infarctions. It is concluded that patients dying following VAD have commonly suffered perioperative myocardial infarction. When evaluating complications associated with VAD, one should consider that the true incidence of thromboembolic events is underestimated by clinical findings. PMID- 1457951 TI - Dialysate and blood flow dependence of diffusive solute clearance during CVVHD. AB - To define the flow dependence of diffusive solute clearance (Kd) during continuous venovenous hemodiafiltration (CVVHD), urea, creatinine, and phosphate clearance were measured during CVVHD, while ultrafiltration was minimized. Studies were performed using AN69, polyacrylonitrile (PAN), and polyamide (PA) hollow fiber hemofilters. To assess the dialysate flow dependence of Kd, clearances were measured at constant blood flow (QB), while dialysate inflow (QDi) was increased incrementally from 8.3 to 33.3 ml/min. Kd increased linearly for all three solutes using all membranes. To assess its blood flow dependence, Kd was measured at blood flows of 50, 75, 100, and 150 ml/min, while QDi was held constant at 33.3 ml/min. The PA membrane showed no flow dependence; for the other membranes, Kd was flow independent for QB > 100 ml/min. At all values of QB and QDi, clearances for the AN69 and PAN membranes were two to three times that of the PA membrane (p < 0.01). Lactate uptake increased with increasing QDi for all three membranes, but did not result in blood lactate accumulation. It is concluded that: 1) small molecule clearance is dialysate flow limited during CVVHD; 2) increasing QB beyond 100 ml/min is unnecessary for maintaining solute clearance; and 3) the PA membrane is unsuitable for CVVHD because of its low diffusive solute clearance. PMID- 1457952 TI - Solute clearance in continuous venovenous hemodialysis. A comparison of cuprophane, polyacrylonitrile, and polysulfone membranes. AB - Critically ill patients with ARF and MOSF were treated with continuous venovenous hemodialysis (CVVHD). The BSM 22 delivery system (CGH Medical, Denver, CO) and four different dialyzer membranes were used. Vascular access was achieved with a dual lumen catheter placed percutaneously into a large vein. Heparin was used for anticoagulation, and commercially available peritoneal dialysis fluid was used as dialysate. At a fixed blood flow rate of 100 ml/min, the dialysate inflow and outflow rates were regulated to control azotemia and fluid balance. Blood side and dialysate side clearances for urea nitrogen, creatinine, bicarbonate, and lactate were measured. All dialyzer membranes studied provided high urea nitrogen clearance approximating dialysate outflow rate and resulting in excellent control of azotemia. Some of the dialyzer membranes also had high creatinine and bicarbonate clearances. Bicarbonate loss was balanced by lactate uptake with all dialyzers. It is concluded that CVVHD is an efficient and safe therapy for acute renal failure, capable of maintaining nitrogen balance in patients with protein catabolic rates up to 2 g/kg/day. Urea nitrogen clearance is dependent upon dialysate outflow rate rather than the dialyzer membrane type or dialyzer flow geometry, and may prove to be the modality of choice for therapy of acute renal failure in unstable patients with MOSF. PMID- 1457953 TI - Non-thrombogenic hemofiltration system for acute renal failure treatment. AB - Continuous arteriovenous hemofiltration (CAVH) has become an accepted therapy for patients with acute renal failure. A major technical concern with CAVH is clotting of the hemofilter, resulting from blood-material interactions. This study compares the thromboresistance and performance characteristics of a Duraflo II heparin treated CAVH circuit with those of an untreated control circuit. The circuit consisted of a polysulfone hemofilter, tubing sets, and catheters. The heparin treatment did not change the mass transfer properties of the hemofilter. The thromboresistance of the heparin treated circuit was compared directly with that of an untreated circuit in a heparinless sheep model using bilateral circuits. The heparin treatment significantly enhanced the blood compatibility of the circuit, as indicated by the reduction in thrombus formation, prolonged work life, and superior performance in heparinless sheep. There was minimal heparin leaching from the hemo-filter. A heparin treated circuit may improve the safety and effectiveness of the CAVH procedure, and offers potential for a systemic heparin protocol to be modified for patients with bleeding disorders. PMID- 1457954 TI - An electrically powered total artificial heart. Over 1 year survival in the calf. AB - An electric motor driven orthotopic artificial heart was implanted in a 110 kg female Holstein calf as part of a series of 12 such implants intended to demonstrate the in vivo durability and compatibility of the device. The device uses pusher plates set into motion by a reversing brushless DC motor and roller screw to alternately eject two cylindrical sac type blood pumps. The pumps use Bjork-Shiley Delrindisc convexo-concave or monostrut valves. The left pump provides an 88-90 ml dynamic stroke volume. Woven Dacron grafts and polyurethane coated Dacron/Lycra cuffs are used to attach the device to the major arteries and atria, respectively. A polyurethane conduit and anchoring skin button bring motor wires percutaneously to an extracorporeal controller. The controller provides balanced cardiac output sensitive to atrial or aortic pressures, without operator intervention. The system is hermetically sealed and uses a simple compliance sac to maintain thoracic pressure between the pumps. The calf recovered uneventfully from surgery and thrived thereafter. She was killed on the 388th post-operative day because of worsening cardiac insufficiency. The previous three operative survivors in this series lived 131, 134, and 204 days. These results indicate the device's good potential for durability and body compatibility. PMID- 1457955 TI - Development of a totally implantable artificial heart. AB - The first generation of an integrated, totally implantable electrohydraulic total artificial heart was designed for long-term cardiac replacement. The system consists of an elliptical blood pump with an interatrial shunt, Medtronic-Hall 27 mm and 25 mm inflow and outflow valves, respectively, an energy converter consisting of an axial-flow, hydraulic pump driven by a brushless DC motor, and an electronics system with transcutaneous energy transmission and telemetry. Energy is supplied by internal nickel-cadmium rechargeable batteries that supply power for 20 min and external silver-zinc batteries that are designed to supply energy to run the system for 5 hr. The blood pump consists of a single layer diaphragm cast from Biolon, with joined right and left ventricles sharing a common base. The dynamic stroke volume is 84 ml, and maximum cardiac output is 9.2 L/min at a heart rate of 110 beats/min on the mock circulation. A 4.3 mm diameter interatrial shunt is used to balance the volumetrically coupled ventricles. The energy converter pumps hydraulic fluid alternately between ventricles, with controlled, active filling in one ventricle during the systolic phase of the other ventricle. Internal or external controllers adjust the heart rate and motor speed to maintain normal atrial filling pressures and full stroke. Electromagnetic induction is used to transfer energy through the skin and a bidirectional infrared data link incorporated within the transcutaneous energy transmission coils is used to transmit information. The entire system is being assembled and refined for long-term animal implant studies. PMID- 1457956 TI - The second and third model of the flow transformed pulsatile total artificial heart. AB - For the purpose of future total implantation, a new pulsatile total artificial heart, a flow transformed pulsatile total artificial heart (FTPTAH), in which the continuous flow from a single centrifugal pump (CFP) was converted to pulsatile flow by switching two three-way valves that could alternately perfuse the systemic and pulmonary circulation, was proposed, and the data from the prototype model were reported. As the next step, the second model, in which a CFP and a spool valve (SV) driven with a solenoid were fabricated in one piece, was made and tested in a mock circulatory system. The system could send 4.7 L/min of pulsatile output alternately to the pulmonary artery and aorta, with 30 and 100 mmHg afterload, respectively, at 3000 rpm CFP. However, three problems were encountered: the output was not enough, mixture or inversion of venous and arterial blood in the CFP would occur, and heat generation at the solenoid was very severe. To solve these problems, a third model was designed in the current study. To increase pump output, hydrodynamic analysis was performed. The SV was divided into inlet and outlet to control the blood mixture or inversion. To suppress heat generation, each SV was driven back and forth by two solenoids, one on each side of the SV. The model revealed satisfactory results in a mock circulatory system. PMID- 1457957 TI - In vitro assessment of the Milwaukee Heart and right to left balance. AB - A new, electrically powered, total artificial heart, the Milwaukee Heart, has been developed. This device is undergoing testing in vitro. The unidirectional motion of the brushless DC motor (BDCM) affords easier motor control and reduces energy demand. Motors with a unidirectional motion have a longer life than those with bidirectional motion. This device requires less power due to the highly efficient mechanical design. It consumes 6.5 W of power at an average flow of 5 L/min into 100 mmHg of mean aortic pressure and 20 mmHg of mean pulmonary pressure. Pumping at 8 L/min it requires 9.6 W of power. The maximum pump flow is 10 L/min and overall efficiency is 20%. A slotted optocoupler is used to determine the position of the pusher plate at the start of left systole. The number of revolutions that the BDCM makes is counted from this position. There are 50 revolutions of the BDCM per stroke (using a 50:1 gear reducer connected to the motor). The position of the pusher plate is determined from the number of BDCM revolutions. Based on where the pusher plate encounters resistance from the bladder, the force on the left pump is increased or decreased. Left to right balance has been achieved by reducing the size of the right pusher plate in conjunction with varying right stroke volume. In vitro tests show that this new, electrically powered artificial heart provides reliable performance and satisfactory hemodynamic results. PMID- 1457958 TI - Achievement of physiologic pulsatile flow on cardiopulmonary bypass with a 24 French cannula. AB - In 1990, the NIH formally recognized the need for investigation of the problem of damaging the effects of cardiopulmonary bypass, issuing RFA HL-90-12-H, which emphasized production of neurologic defects in the very young and the elderly. The authors were at that time involved in comparison of pulsatile flow to steady flow cardiopulmonary bypass in large ungulates. The world literature recognizes five damaging effects of steady flow cardiopulmonary bypass that can be mitigated by pulsatile flow: metabolic acidosis, interstitial fluid accumulation, elevated systemic vascular resistance, arteriovenous shunting, and impaired brain oxygenation. To maximize the beneficial effect of pulsatile flow, however, it is necessary that its morphology be physiologic. It has been stated in the past that this goal may not be possible using standard size aortic cannulas. The purpose of this publication is to describe a method by which this feat has been achieved in 150 pound ungulates undergoing prolonged cardiopulmonary bypass. PMID- 1457959 TI - Studies on the electrical stimulation-induced contractile responses of hamster and mouse gallbladders. AB - Isolated gallbladders of both hamsters and mice showed a contractile response consisting of initial and secondary contractile responses to electrical stimulation with rectangular pulses (50 volt, 40 Hz) of 6 msec duration for a period of 10 seconds. The duration time of the contractile response was very long. This was because the duration time of the process of the initial contractile response was as short as 5 to 40 seconds, but that of the secondary contractile response was as long as 8 to 15 minutes. Both initial and secondary contractile responses of the gallbladder in both hamsters and mice were little affected by atropine (1 x 10(-6)M, guanethidine (1 x 10(-6) M) and tetrodotoxin (1 x 10(-7) M). In both animals, further, the initial contractile response of the gallbladder was little affected by indomethacin (1 x 10(-5) M) and 5, 8, 11, 14 eicosatetraynoic acid (ETYA) (5 x 10(-6) g/ml), while the amplitude of the secondary contractile response of the gallbladder was significantly reduced by such drugs. From these results, we obtain the following conclusions: 1) In both animals, the intramural nerves of the gallbladder may have no influence on the both initial and secondary contractile responses of the gallbladder. 2) The initial contractile response is probably mediated by a direct effect of the electrical stimulation to the muscle in the wall of the gallbladder, while the secondary contractile response is probably attributable to prostaglandins released from the wall of the gallbladder by a direct effect of the electrical stimulation to the wall. PMID- 1457960 TI - [Effects of trimebutine on colonic propulsion in mice]. AB - Effects of oral administration of trimebutine on colonic propulsion in conscious mice were studied by measuring the time required to evacuate a bead which had been inserted into the colon, and compared with those of metoclopramide and domperidone. In normal animals, trimebutine (10 and 50 mg/kg), metoclopramide (50 mg/kg) and domperidone (50 mg/kg) had no effect on the bead evacuation. Metoclopramide and domperidone at 30 mg/kg showed no effect on the delay of colonic propulsion induced by clonidine, while trimebutine (10 and 30 mg/kg) restored the delay significantly. Trimebutine also showed restoration of the delay induced by loperamide. On the acceleration of the propulsion induced by neostigmine, trimebutine (10 and 30 mg/kg) showed an inhibition. In addition, trimebutine (3-30 mg/kg) dose-dependently suppressed the development of soft feces and/or diarrhea induced by neostigmine. According to the results, it is concluded that trimebutine produces both acceleration and inhibition on the colonic propulsion in mice. PMID- 1457961 TI - [Electrical activities of urethral circular muscle and bladder detrusor and their control, examined by in vivo dogs]. AB - While the micturition reflex was induced in dog by infusion of Ringer solution into the bladder, the following four types of electrical activity were picked up by two bipolar wire electrodes, embedded in the posterior wall of bladder and in the prostatic part of male urethra; 'intravesical ureter potential' and 'detrusor spike' by bladder electrode, and 'slow wave' and 'external sphincter spike' by urethral electrode. The relative size, respective rhythm and timing of discharge during voiding cycle were specific for each of them and they were readily identifiable for their own sources. The 'ureter potential' was not actively related to the voiding cycle but its triphasic wave form was dissociated at the maximum contraction phase of the bladder. Unexpected finding was the 'quasi synchronization' of discharges between detrusor and external sphincter. The entire discharges in both muscles were consisted of 'initial burst', 'intermittent inhibition' and 'prolonged after-discharge'. The initial burst of detrusor was definitely delayed in comparison with that of external sphincter, but the end of prolonged after-discharges was again synchronized in both muscles. The possible mechanism for synchronization was discussed. The 'slow wave' was sometimes superposed on the tonic discharge of external sphincter recorded by same wire-electrode in urethral wall, therefore, their properties were analyzed under the condition of 'immobilization' of external sphincter. The sustained waxing and waning 'slow waves', observed in all female urethrae and one-fifth of male urethrae, were markedly suppressed by elicitation of isovolumetric rhythmic contractions of bladder with fall of intraurethral pressure. This bladder dependent behavior of 'slow wave' was interpreted as a sign of 'urinary' sphincteric activity of urethral circular muscle. On the other hand, 'spontaneous' cyclic activation of 'slow wave' which was seen in about four fifths of male urethrae and was not dependent upon the state of bladder, was interpreted as a sign of 'genital' sphincteric activity of the same circular smooth muscle. PMID- 1457962 TI - Haemopoietic tissue. PMID- 1457963 TI - Growth factors in haemopoiesis. Dedicated to the memory of Dr. John Freeman Loutit. PMID- 1457964 TI - T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction. AB - Interleukin 2 (IL-2)-induced tyrosine phosphorylation appears to play a major role in IL-2-induced cellular proliferation. Several intracellular substrates including the beta chain of the IL-2 receptor complex (IL-2R beta), raf, MAP2 kinase, the regulatory 83 kDa subunit of phosphatidylinositol-3 kinase and S6 kinases are substrates for the IL-2 receptor activated kinase(s). However, none of the identified members of the IL-2 receptor complex exhibits intrinsic tyrosine kinase activity. Therefore, the IL-2R complex must activate intracellular tyrosine kinases. We have demonstrated that specific tyrosine and serine/threonine kinases are coprecipitated with IL-2 receptor constructs that mediate IL-2-induced cell proliferation but not with those that do not. The IL-2 activated tyrosine kinase appears to be associated with a serine and proline rich intracellular domain which is highly conserved between IL-2R beta and the erythropoietin receptor. Although the responsible kinase has not been identified, lck, fyn, fgr, ltk, hck and lyn can be ruled out as obligatory mediators. Using methods to clone tyrosine kinases from T cells, we have identified potential candidate kinases, including several which had not been known to be expressed by T lymphocytes as well as several unique kinases which had not been previously identified in any cell type. PMID- 1457965 TI - Cell adhesion in the stromal regulation of haemopoiesis. AB - Haemopoiesis occurs in close physical contact with elements of the bone marrow stroma. This review examines some adhesion molecules which are expressed in haemopoietic environments. These molecules may act to maintain cell contact between haemopoietic progenitors and the cellular and extracellular matrix elements of the marrow stroma. A review is undertaken of several families of adhesion molecules and their ligands, including integrins, CD44, LEC-CAMs, CAMs and variant glycosylation patterns expressed by haemopoietic cells. Both CD44 and integrin receptors have been implicated in mediating important cellular interactions within the haemopoietic system and the significance of these and other molecules in haemopoiesis is discussed. PMID- 1457966 TI - Stem cell proliferation inhibitors. PMID- 1457967 TI - Growth restrictions in the regulation of haemopoiesis. PMID- 1457968 TI - Clinical uses of growth factors. AB - The haemopoietic growth factors are a diverse group of hormones with effects on different haemopoietic cell lineages and at various points in their developmental differentiation. The biology of many of these factors is now well understood. They have entered clinical trials and have demonstrated benefits in particular clinical situations. The thrust of current phase II and III clinical investigations now is to use these factors, alone or in combinations, to modify various disease states and to ameliorate many of the side-effects of other therapeutic agents, particularly cytotoxic anticancer agents. Many other disease states also lend themselves to therapy with these growth factors. Other haemopoietic growth factors have not been as extensively studied in humans but hold great promise. In this chapter, the current status of the haemopoietic growth factors presently under clinical trial has been reviewed. In addition, several factors which have been recently described but which have not yet entered clinical trials have been discussed. PMID- 1457969 TI - The asparagine-linked oligosaccharides at individual glycosylation sites in human thyrotrophin. AB - The asparagine-linked carbohydrate structures at each of the three glycosylation sites of human thyrotrophin were investigated by 400 MHz 1H-NMR spectroscopy. Highly purified, biologically active human thyrotrophin (hTSH) was dissociated into its subunits hTSH alpha (glycosylated at Asn 52 and Asn 78) and hTSH beta (glycosylated at Asn 23). The alpha-subunit was further treated with trypsin which gave two glycopeptides that were subsequently separated by reverse-phase HPLC and identified by amino acid sequence analysis. The oligosaccharides were liberated from hTSH alpha glycopeptides and from intact hTSH beta by hydrazinolysis, and were fractionated as alditols by anion-exchange and ion suppression amine-adsorption HPLC preparatory to structural analysis. The N glycans present on hTSH were mainly diantennary complex-type structures with a common Man alpha 1-3 branch that terminated with 4-O-sulphated GalNAc. The Man alpha 1-6 branch displayed structural heterogeneity in the terminal sequence, with chiefly alpha 2-3-sialylated Gal and/or 4-O-sulphated GalNAc. The relative amounts of the two major complete diantennary oligosaccharides and their core fucosylation differed according to glycosylation site; the sulphated/sialylated diantennary oligosaccharide was most abundant at the two sites on the alpha subunit, whereas the disulphated, core-fucosylated oligosaccharide was more plentiful on the beta-subunit. Some interesting structural features, not previously reported for the N-glycans of hTSH, included 3-O-sulphated galactose (SO4-3Gal) and peripheral fucose (Fuc alpha 1-3GlcNAc) in the Man alpha 1-6 branch of some diantennary structures; the former suggests the presence of a hitherto uncharacterized galactose-3-O-sulphotransferase in thyrotroph cells of the human anterior pituitary gland. PMID- 1457970 TI - Structure elucidation of sulphated oligosaccharides from recombinant human tissue plasminogen activator expressed in mouse epithelial cells. AB - Sulphated N-linked carbohydrate chains isolated from recombinant human tissue plasminogen activator expressed in mouse epithelial (C127) cells were analysed as oligosaccharide alditols by methylation analysis, liquid secondary ion mass spectrometry, and one- and two-dimensional 1H-NMR spectroscopy. The results demonstrate that the major component has the following novel structure: NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-2[NeuAc alpha 2-3Gal beta 1- 4GlcNAc beta 1-4] Man alpha 1-3[NeuAc alpha 2-3(SO4-6)Gal beta 1- 4-GlcNAc beta 1-2Man alpha 1-6] Man beta 1-4GlcNAc beta 1- 4[Fuc alpha 1-6]GlcNAc-o1. PMID- 1457971 TI - Characterization of recombinant murine interleukin 5 expressed in Chinese hamster ovary cells. AB - We have purified recombinant murine interleukin 5 (rmIL-5) from the supernatant of Chinese hamster ovary cells. Each peptide fragment of the purified rmIL-5 generated by Achromobacter protease I digestion was characterized and glycosylation sites were determined. Although rmIL-5 contains three potential sites of N-linked glycosylation (Asn-26, Asn-55 and Asn-69), Asn-69 is not glycosylated. The oligosaccharides released from the protein by hydrazinolysis were fractionated by paper electrophoresis, lectin column chromatography and gel permeation chromatography, and their structures were analysed by sequential exoglycosidase digestion in combination with methylation analysis. The results indicated that they are a mixture of bi-, tri- and tetraantennary complex-type sugar chains with and without a fucose at the C-6 position of the proximal N acetylglucosamine residue and high-mannose-type sugar chains. Although > 80% of the sugar chains are neutral oligosaccharides similar to recombinant human IL-5 (rhIL-5; Kodama, S., Endo, T., Tsuroka, N., Tsujimoto, M. and Kobata, A. (1991) J. Biochem., 110, 693-701), rmIL-5 has more tetraantennary oligosaccharides than rhIL-5. A site differential study revealed that Asn-55 has more tetraantennary oligosaccharides than Asn-26. PMID- 1457972 TI - Tritiated borohydride reduction of carbohydrates: reduction of individual monosaccharides, alone or in groups, results in highly divergent specific activities. AB - Reduction of carbohydrates by tritiated borohydride resulted in the production of alditols or glycosides with characteristically divergent specific radioactivities. Simultaneous reduction of individual sugars in the presence of a reference standard, talose, permitted the assignment of a unique specific radioactivity with respect to talitol as 100%. A variety of structures was examined, including neutral hexoses, free and acetylated aminosugars, ketohexoses and glycosides containing a fixed pyranose ring adjacent to a carbonyl group. In the latter case, the resulting steric hindrance severely restricted the incorporation of tritium. In both of the ketohexoses tested, the minor product of the two epimeric alditols exhibited the higher specific radioactivity. In all cases, reduction produced a characteristic and reproducible specific activity in which the values varied from 51 to 182% of that found for talose. These results are interpreted on the basis of generalizations concerning mechanism and predictive value. PMID- 1457974 TI - 21st Annual Meeting of the Society for Complex Carbohydrates. Nashville, Tennessee, November 11-14, 1992. Abstracts. PMID- 1457973 TI - Schistosoma mansoni synthesizes novel biantennary Asn-linked oligosaccharides containing terminal beta-linked N-acetylgalactosamine. AB - This report describes the structure of novel complex-type Asn-linked oligosaccharides in glycoproteins synthesized by the human blood fluke, Schistosoma mansoni. Adult schistosome worm pairs (male and female) isolated from infected hamsters were metabolically radiolabelled with either [3H]glucosamine, [3H]mannose or [3H]galactose. The glycopeptides prepared by pronase digestion of the total glycoprotein fraction were isolated by affinity chromatography on columns of immobilized Concanavalin A (Con A) and Wisteria floribunda agglutinin (WFA). A subset of glycopeptides, designated IIb, that bound to both Con A and WFA was isolated. WFA has been shown to have affinity for oligosaccharides containing beta 1,4-linked N-acetylgalactosamine (GalNAc) at their non-reducing termini. Compositional analysis of IIb glycopeptides demonstrated that they contained N-acetylglucosamine (GlcNAc), GalNAc, mannose (Man) and fucose (Fuc), but no galactose (Gal) or N-acetylneuraminic acid (NeuAc). Methylation analyses and exoglycosidase digestions indicated that IIb glycopeptides were complex-type biantennary structures with branches containing the sequence GalNAc beta 1-4-[+/- Fuc alpha 1-3]GlcNAc beta 1-2Man alpha 1-R. The discovery of these unusual oligosaccharides synthesized by a human parasite, which appear to be similar to some newly discovered mammalian cell-derived oligosaccharides, may shed light on future studies related to the role oligosaccharides may play in host-parasite interactions. PMID- 1457975 TI - Iron-binding proteins in human colorectal adenomas and carcinomas: an immunocytochemical investigation. AB - By immunocytochemistry, the presence of major iron-binding proteins (lactoferrin, transferrin and ferritin) was investigated in tubular adenomas (12 cases), villous adenomas (7 cases), carcinomas of the large bowel and rectum (39 cases) and lymph nodes involved in carcinomas (8 cases); 5 samples of colonic inflammatory pseudopolyps were also studied. Dysplastic areas of tubular and villous adenomas as well as adenocarcinomas and colloid carcinomas showed a variable cytoplasmic immunoreactivity for all antisera, although no staining was noted in some cases; tubular adenomas without dysplasia and colonic inflammatory pseudopolyps were always unstained. Metastatic elements present in lymph nodes maintained the immunohistochemical staining for iron-binding proteins. An autoctone production of lactoferrin, transferrin and ferritin by tumour cells may be hypothesized in relation to the increased requirement of iron for the turnover of rapidly dividing cells. PMID- 1457976 TI - Morphometric study on the renal glomeruli of streptozotocin (SZ)-induced diabetic APA hamsters. AB - Morphometrical analysis was done on the renal glomeruli of streptozotocin (SZ) induced diabetic and control APA hamsters. In coincidence with the histopathological and ultrastructural findings, the areas of whole glomerulus (WG) and mesangial region (MR) were significantly larger in diabetic animals than in controls at 1 and 3 months after SZ-injection (1 and 3MAI). The area of capillary lumen in diabetic animals was larger than that in controls at 1MAI but it became similar between both groups at 3MAI probably due to an increase in the area of MR. The thickness of basement membrane was significantly larger in diabetic animals than in controls at 3MAI. The present morphometrical findings, together with histological and ultrastructural ones, suggest that SZ-induced diabetic APA hamsters are useful as a model system for the investigation of focal and segmental glomerulosclerosis. PMID- 1457977 TI - Experimental induction of biliary cystadenoma in rats: a morphological study. PMID- 1457978 TI - The arterial pattern and fractal dimension of the dog kidney. AB - A method has been developed by which it is possible to measure the fractal dimension of the arterial tree of the kidney. The objective of this work is to determine a method which permits us to discriminate between the architectures of specific organs by reference to a unique number, namely the fractal dimension of the arterial tree of that organ. This method opens the possibility of a new taxonomy for normal organs and for the pathological injiries related to the vascular morphology of those organs. The method that we have devised uses as its input the volume which is taken up by the arterial tree of the kidney. In order to calculate this volume we first obtained a plastic cast (the arteries were filled with Araldite CY233 plastic resin after which the organic tissues were corroded); thereafter we constructed a theoretical arterial tree having the same volume as the renal one. From this simplified tree, we were able to calculate its fractal dimension. The complete process of constructing the theoretical arterial tree and the subsequent calculation of its fractal dimension was carried out automatically by way of a computer programme to which we have given the name fractal program. PMID- 1457979 TI - Role of multipotent fibroblasts in the healing colonic mucosa of rabbits. Ultrastructural and immunocytochemical study. AB - Light- and electron microscopy and immunocytochemistry were used to study the healing colonic mucosa of rabbits after experimental excision. Between 3 and 5 days, abundant young fibroblasts which retained many features of mesenchymal cells invaded the growing capillaries into the loose connective tissue of the healing colonic mucosa. Our electron microscopy revealed the transformation of these young fibroblasts into smooth muscle cells, into histiocyte-like cells involved in phagocytotic activity, and into vasoformative cells incorporated into the growing capillaries. The mitotic proliferation of pre-existing smooth muscle cells at the ulcer margin did not seem to be the major reason for re establishment of the muscular tissue. The present immunocytochemistry revealed an active production of fibronectin in rough endoplasmic reticulum in the young fibroblasts. This may mean that this glycoprotein is involved in the re establishment of both connective and muscular tissues by enhancement of adhesion and chemoattractant activities of such cells. In addition, the immunoreaction of endothelial cells of the growing capillaries suggests a role of this glycoprotein in the acceleration of the neocapillarization. PMID- 1457980 TI - Ontogeny of reactivity to endothelial cell markers during development of the embryonic and fetal rat lung. AB - The reactivity of endothelial cells to putative endothelial cell-specific markers varies with species, with vessel size and with the organ studied. To determine their value in studies of fetal rat lung, and whether organ immaturity would also influence reactivity, we studied endothelial cell immunoreactivity to antibodies against Factor VIII/von Willebrand factor (VIII/vWF), and binding reactivity to Bandeiraea (Griffonia) simplicifolia 1 lectin (BSL 1) during rat fetal lung development. Using an indirect immunofluorescent technique to detect Factor VIII/von Willebrand factor (VIII/vWF), endothelial cells lining the aortic arches were identified as early as day 11 of gestation (term = 22 days), prior to lung development. Immunoreactivity to VIII/vWF was subsequently localized to intrapulmonary endothelial cells and was not dependent on vessel size. In contrast, binding reactivity of FITC-conjugated BSL 1 was observed to both endothelial cells and to the basement membrane of developing airways, thus limiting its value as endothelial cell marker. During very early lung development solitary angioblasts could not be identified by reactivity to either VIII/vWF antibodies or to BSL 1, and neither marker appears to be of value for studies of early angiogenic events. PMID- 1457981 TI - Ultrastructural study of inflammatory bowel disease. AB - Ultrastructural changes that occurred in chronic active ulcerative colitis and Crohn's disease were investigated and compared to normal as well as to higher grades of dysplasia in adenomas and carcinomas. A greater number of immature absorptive cells, undifferentiated and intermediate cells were seen as compared to normal. One case of Crohn's and two cases of chronic ulcerative colitis including one with coexisting carcinoma showed increased number of vesicles and electron-dense bodies (EDB) in the absorptive cells and increased heterogeneity of mucin droplets in goblet cells and presence of atypical secretory cells (ASC). Higher grades of dysplasia characterised by large numbers of atypical secretory cells were not seen in the present series and provide no relationship between the atypical ultrastructural features and increased risk of malignancy. However, the number of cases investigated is too small and a large series is required to clarify the significance of observations such as increased number of electron dense bodies and vesicles in the apical cytoplasm and presence of atypical secretory cells. PMID- 1457982 TI - Ultrastructural study of neuromuscular junction in rectus femoris muscle of streptozotocin-diabetic rats. AB - The neuromuscular junctions (NMJ) from rectus femoris muscle in streptozotocin (STZ)-induced diabetic rats were examined by electron microscopy eight weeks after the STZ injection. When compared to controls and vehicle-injected groups, both the axon terminal and the junctional sarcoplasm showed serious alterations including mitochondrial degeneration, presence of myeloid bodies, breakdown of presynaptic membrane and changes in the form of the synaptic vesicles. The results suggest that NMJ can contribute to the pathogenesis of diabetic proximal myopathy. PMID- 1457983 TI - In vitro differentiation of myxoid liposarcomas maintained in organ culture system. AB - Liposarcoma falls into the differential diagnosis of myxoid malignant mesenchymal tumors. On the other hand, its relation with white or brown fat is controversial. Two cases of liposarcoma have been studied by organ culture, a method which provides cell and tissue redifferentiation in vitro. Both cases developed successively cytoplasmic glycogen granules and lipid droplets as well as a single lipidic vacuole in the late phase of cultivation as a marker of fat differentiation. Our results support the possibility of identifying myxoid liposarcomas as well as their origin from white fat tissue. PMID- 1457984 TI - Murine monoclonal antibodies cytotoxic to human glioma cells in vitro. AB - Six monoclonal antibodies (mABs) against human glioma cells (T2) were produced. T2 cells grown as solid tumors in nude mice, were dissociated and used to immunize Balb/c mice. After fusion of splenocytes with myeloma cells, eight hybrids secreting mABs were selected according to their ability to react immunohistochemically with T2 cells, but not with normal adult human brain. Cytotoxicity of mABs was tested using (3H)-thymidine incorporation assays in vitro. Four mABs showed complement-mediated cytotoxicity for T2 cells, other human glioma cells (T1), and a human melanoma cell line. Incubation with one antibody, mAb2A1, lowered (3H)-thymidine incorporation in the T2 and T1 cells to ca. 10%, and in melanoma cells to ca. 35% of control levels. Another antibody, mAb3B2, displayed a similar cytotoxicity for T2 and T1 cells, but did not show measurable cytotoxicity for melanoma cells and rat primary astrocyte cultures. Moreover, this antibody did not crossreact with haematopoietic cells from patients bearing CNS tumors or normal subjects. MAb3B2, therefore, appears to recognize and epitope associated to human gliomas, will be a useful glioma tumor marker and may have some potential therapeutical value. PMID- 1457985 TI - Radiohistology and histochemistry of barium granuloma of the colon and rectum. AB - Barium granuloma of the colon and rectum is a rare complication of X-ray examination of the digestive tract using barium. The authors report 5 new cases occurring in the last 3 years. Histological examination revealed a granulomatous reaction with greyish finely granular refractile PAS-negative material located in the cytoplasm of histiocytes and in the interstitial space. The radiographic study of the paraffin blocks confirmed the nature of this material, which was X ray opaque, and this was corroborated histochemically with the rhodizonate technique. PMID- 1457986 TI - Seeding of expanded polytetrafluoroethylene (ePTFE) vascular grafts. A morphological study of porcine endothelial and fibroblast cells. AB - The need to improve clinical results with small and medium calibre grafts has led to extensive research on cell seeding of prosthetic materials. Numerous problems remain regarding identification, seeding, adhesion and survival of the cells attached. We have studied the behaviour of seedings of endothelial and fibroblast cells on ePTFE grafts. Scanning electron microscopy allows us to observe the morphological characteristics and their interaction with the biopolymers. It has been possible to differentiate both cellular types by their characteristics and interactions with the ePTFE. At the same time, from this "in vitro" study it can be concluded that the time needed to obtain a stable and confluent monolayer on ePTFE pretreated with fibronectin is between 18 hours to 4 days for endothelial cells, and 24 hours for fibroblasts. These would be the optimal time periods for "in vivo" grafting of the seeded prostheses. PMID- 1457987 TI - Immunohistochemical localization of glial fibrillary acidic protein (GFAP) in rat pineal stalk astrocytes. AB - In the present work, the presence and distribution of astrocytes in the rat pineal stalk is investigated applying an immunohistochemical technique for the demonstration of glial fibrillary acidic protein (GFAP) on Epon-embedded semithin sections (0.5 micron thick). GFAP-immunoreactive cells are evenly and regularly distributed along the entire pineal stalk. The GFAP-immunoreactive cells display a stellate shape showing variable numbers of cell processes that are mainly oriented parallel to the longitudinal stalk axis. Astrocytic processes show a clear tendency to encircle the remaining elements of the pineal stalk; i.e., pinealocytes, nerve fibres and blood vessels. Furthermore, glial processes form a cover layer separating the stalk from surrounding anatomical structures. PMID- 1457988 TI - Expression of neuronal and glial markers in so-called oligodendroglial tumors induced by transplacental administration of ethyl-nitrosourea in the rat. AB - A series of 18 tumors with histological features of oligodendrogliomas, induced in the rat by means of transplacental ethyl-nitrosourea administration were studied for immunohistochemical demonstration of neuronal (synaptophysin and neurofilament protein) and glial (gliofibrillar acidic protein and vimentin) markers. Most of the tumors showed cells with strong positivity to synaptophysin and to a lesser degree, to neurofilament protein, suggesting the neuronal character of these neoplasms. In 10 tumors, cells with strong positivity to vimentin were found, and in three cases, tumoral cells expressed gliofibrillar acidic protein. The observation that ENU-induced oligodendroglial tumors express neuronal and, to a minor degree, glial markers, suggests their interpretation as primitive neuroectodermal tumors with clear neuronal differentiation. PMID- 1457989 TI - Stereological study of the synaptic profiles belonging to interneurons in the dorsal lateral geniculate nucleus of the rabbit. AB - This study is concerned with some characteristics of the interneurons belonging to the dLGN (dorsal Lateral Geniculate Nucleus) of the rabbit. The work deals with the distribution of such cells in the alpha E sector of the nucleus and their F1 and F2 presynaptic contacts. The F1 and the F2 profiles are present in all three of the alpha E zones studied. The F1 profiles are significantly more numerous in the upper zone (57 +/- 2 profiles per 10(4) microns2 of section) and the middle zone (59 +/- 3 profiles per 10(4) microns2 of section) than in the lower one (41 +/- 2 profiles per 10(4) microns2 of section). The F2 profiles are more abundant in the alpha E sector than the F1 ones are, particularly in the lower zone, where F2 profiles (104 +/- 4 profiles per 10(4) microns2 of section) are not only significantly more numerous than F1 profiles but also more abundant than the F2 profiles in the middle zone (84 +/- 3 profiles per 10(4) microns2 of section) and upper zone (88 +/- 2 profiles per 10(4) microns2 of section). These results and their comments reveal diverse density of the element distribution from the dorsal to the ventral part of the alpha E sector as well as the possible relationship or independence from the extranuclear afferent inputs. PMID- 1457990 TI - Circadian and seasonal cortico-medullary variations in pinealocyte nuclear size. A comparative statistical analysis. AB - Circadian and seasonal variations were observed in the karyometric index of pinealocytes in the cortical and medullary regions of the distal pineal body. The study involved 70 Wistar rats over a 24-hour interval (0:6, 10:00, 14:00, 18:00, 22:00, 02:00, 06:00 h) during two natural photoluminous periods, i.e. late summer (Long photoperiod) and Winter (Short photoperiod). The results show a difference between the high and low points of both photoperiods. Cortico-medullary differences are found at different times of day during long photoperiod (0:6; 10:00; 14:00 and 18:00 h.) and short photoperiod (14:00; 22:00 and 02:00 h.). The variance analyses between nuclear volume and point-time and between nuclear volume, point-time and location are significative. A high correlation between circadian rhythms and volumetric variations in both layers and photoperiod are found. The results also show significant differences in cortico-medullary karyometric indices between both seasons as well as between the diurnal and nocturnal hours of both photoperiods. It is suggested that the pineal body of the rat is influenced by circadian and seasonal photoperiod and may have groups of cells with different functional characteristics, depending on their location within the gland. PMID- 1457991 TI - Lack of intimal hyperplasia response in an experimental model of non-endothelial vascular wall damage. AB - The endothelial and medial layers are generally presumed to play an important role in the appearance and development of intimal hyperplasia. We have carried out a short-, media- and long-term study of the morphological changes taking place in the common iliac artery of rats after surgical removal of the adventitial layer. Our aim has been to assess the likely role played by this layer in the development of intimal hyperplasia. Our results show recurrent periods of cellular desquamation and almost complete absence of hyperplastic response during the first two months. After three months three is a slow process of endothelialization which is completed by the 6th month and persists one year after adventitial resection. Thus, adventitial resection seems to cause instability at the subendothelial bed level, not allowing the junction and embedding of endothelial cells nor the development of intimal hyperplasia. This lack of hyperplasia might also result from the fact that the endothelial desquamation process does not involve cellular rupture, which would prevent mitogenic-factor release. After morphological repair of the endothelium, a slow morphofunctional recovery of the artery takes place. PMID- 1457992 TI - An autopsy case of tuberous sclerosis. Histological and immunohistochemical study. AB - We report an autopsy case of tuberous sclerosis. A 19-year-old Japanese man had shown facial adenoma sebaceum, intractable convulsive seizures and severe mental retardation. Gross inspection of the brain showed a cortical tuber from the orbital frontal lobe to the rhinencephalon of the left side and a few subependymal nodules. Histological examination revealed many cortical tubers in the cerebral hemispheres, a few subependymal nodules with calcification and multifocal clusters of heterotopic cells in the white matter (white matter nodules). In these lesions, massive giant cells with abundant eosinophilic cytoplasm and without Nissl substances were found. Although the size and shape of the giant cells were variable, the majority of them were gemistcytic, ovoid or polygonal. Immunohistochemistry was employed in these lesions using antibodies against neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), vimentin (VM) and myelin basic protein (MBP). In the cortical tuber, the majority of the giant cells were positive for both NFP and VM, but a few were positive for GFAP. All of them were negative for MBP. In the subependymal nodule and white matter nodule, the majority of the giant cells were positive for NFP, but a few were positive for VM, and none were positive for either GFAP and MBP. These findings suggest that the majority of the giant cells may be immature cells toward neuronal series and a few may be those toward astroglial series. These findings also indicate that the giant cells in the subependymal nodule and white matter nodule may be more differentiated than those in the cortical tuber. The nature of the giant cells in tuberous sclerosis is discussed. PMID- 1457993 TI - An in vitro study on the effects of melatonin on the ultrastructure of the hamster parathyroid gland. AB - Isolated parathyroid glands from adult female golden hamsters were incubated on a black Millipore filter in an incubation vessel containing Ham's F-12 medium, with or without melatonin at final concentration of 10(-5) M for 1 hour. In the parathyroid glands used for in vitro treatments with melatonin, the Golgi complexes associated with a few prosecretory granules and cisternae of the rough endoplasmic reticulum showed a significant decrease, and lipid droplets and lysosomes appeared to be increased compared with those of the control parathyroid glands. These changes are considered to be induced by suppression of the synthesis of parathyroid hormone in parathyroid glands incubated in a vessel containing medium with melatonin. PMID- 1457994 TI - Sex-specific response of the vasopressin-reacting neurons of the paraventricular nucleus of the rat hypothalamus following chronic administration of met enkephalin. AB - Using the peroxidase-antiperoxidase immunocytochemical technique, a morphometric study of the magnocellular neurons of the Paraventricular nucleus of the rat hypothalamus, reactive to specific anti-vasopressin rabbit serum, was made. Following systemic and chronic administration of met-enkephalin the number of immunoreactive neurons was higher, especially in females. Additionally, in the females, it was possible to observe an increase in the immunoreactivity and the presence of well-stained fibres. These findings suggest, especially in females, a blockage in the release of vasopressin, facilitating its immunocytochemical visualization. PMID- 1457995 TI - Lesion and regeneration in the medial cerebral cortex of lizards. AB - The cerebral cortex of Squamate reptiles (lizards and snakes) may be regarded as an archicortex or "reptilian hippocampus". In lizards, one cortical area, the medial cortex, may be considered as a true "fascia dentata" on grounds of its anatomy, connectivity and cyto- chemo-architectonics of its main zinc-rich axonal projection. Moreover, its late ontogenesis and postnatal development support this view. In normal conditions, it shows delayed postnatal neurogenesis and growth during the lizard's life span. Remnant neuroblasts in the medial cortical ependyma of adult lizards seasonally proliferate. The late-produced immature neurocytes migrate to the medial cortex cell layer where they differentiate and give off zinc-containing axons directed to the rest of cortical areas. This results in a continuous growth of the medial cortex and its zinc-rich axonal projection. Perhaps the most important characteristic of the lizard medial cortex is that it can regenerate after having been almost completely destroyed. Recent experiments in our laboratory have shown that chemical lesion of its neurons (up to 95%) results in a cascade of events; first, those related with massive neuronal death and axonal-dendritic retraction and, secondly, those related with a triggered neuroblast proliferation and subsequent neo-histogenesis, and the regeneration of an almost new medial cortex that shows itself undistinguishable from a normal undamaged one. This is the only report to our knowledge that an amniote central nervous centre may regenerate by new neuron production and neo histogenesis. Perhaps the medial cortex of lizards may be used as a model for neuronal regeneration and/or transplant experiments in mammals or even in primates. PMID- 1457996 TI - Demographic characteristics of a population of people with moderate, severe and profound intellectual disability (mental handicap) over 50 years of age: age structure, IQ and adaptive skills. AB - Studies characterizing community populations of older people with intellectual disability (mental handicap) have frequently derived data from mental handicap registers. Such large-scale studies permit the establishment of reliable age trends, yet may utilize unreliable information and omit some individuals. Here, a functional characterization of a 50+ years sample with moderate, severe and profound intellectual disability is described, in which an extensive outreach exercise to identify individuals not known to mental handicap service providers ensured that almost 100% of people fulfilling the residence, age and ability criteria were included. Functional level, assessed by the Adaptive Behaviour Scale (ABS), is reported in relation to six factors derived from factor analysis. Overall, the sample was relatively high functioning and generally free of severe problem behaviours. There was no evidence for significant age-related functional decline. PMID- 1457997 TI - A preliminary analysis of environmental variables affecting the observed biobehavioural states of individuals with profound handicaps. AB - Recently, various researchers have recommended investigation of biobehavioural states as a worthwhile endeavour toward providing a more valid assessment of students with profound handicaps. To date, the research conducted in this area has largely focused on the biobehavioural state variable in isolation. This pilot study was conducted to examine the relationships between environmental variables and biobehavioural state variables. Six students with profound handicaps were selected as subjects and observed during normal daily school routines. The investigators discovered significant relationships between the students' prior state, position, grouping type of staff cue given, the proximity of the staff and type of activity stimulus provided, and the students' biobehavioural states. A discussion of the results and recommendations for future research are provided. PMID- 1457998 TI - Cognitive profiles in adolescents with mental retardation. AB - Cognitive profiles of performance were obtained from a selected group of adolescent subjects with mental retardation (MR) (n = 32; mean age: 15.4 years, S.D. = 3.7) by means of an ad hoc neuropsychological battery. On the basis of each subject's IQ, the experimental sample was divided into three homogeneous subgroups (severely, moderately and mildly retarded) and cognitive performances obtained in the battery tests were compared. Subsequently, in order to clarify the qualitative aspects of MR, the cognitive patterns of subjects with the same IQ and chronological age were examined. Altogether, from a neuropsychological point of view, the results of this study seem to support the hypothesis that MR is a heterogeneous condition of cognitive deficits (some abilities are better preserved than others) and indicate that a set of multiple tests exploring single cognitive functions is needed in order to describe cognitive profiles in MR. PMID- 1457999 TI - Dexamethasone suppression test and response to antidepressants in depressed mentally handicapped subjects. AB - Nineteen mentally handicapped subjects who were referred to the service with clinically significant depression were assessed with a view to determining the value of the dexamethasone suppression test (DST) in clinical diagnosis and in predicting response to antidepressant treatment. They were assessed initially and then 3 months after they had been treated with a tricyclic antidepressant. It was found that a significant proportion had an abnormal DST response which reversed after recovery in some but not in others. Non-reversal was more likely to occur in the more severely handicapped patients. It was concluded that DST was of little value as a diagnostic tool for the detection of depression in mentally handicapped subjects. PMID- 1458000 TI - Chromosome fragility in the Lennox-Gastaut epilepsy syndrome. AB - Chromosome fragility was sought in a well-defined cohort of patients with Lennox Gastaut epilepsy syndrome. Twenty-five patients plus 25 age- and sex-matched normal controls had cytogenetic studies performed. All patients were taking sodium valproate, and four were also on hydantoin. Blood cultures from both patients and controls were set up simultaneously in an appropriate medium designed to elicit fragile-sites. Harvesting took place after 96 h by standard techniques. In addition to routine banded analysis, at least 50 cells were scored for chromosome breaks and gaps from each patient and control. Results showed no difference between the patients and the control group in the overall occurrence of fragility or the type of aberration detected. No fragile-X syndrome was detected. This study found no effect due to sodium valproate on the occurrence of chromosome aberrations. PMID- 1458001 TI - Mental retardation and WAIS-R scatter analysis. AB - In an earlier article, the psychometric properties of Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtest difference scores were explored using a sample with IQ < 80. Data were offered which allowed the practitioner to determine whether the difference between two subtests was statistically reliable. This article represents an extension of the earlier work. It presents a set of reliability estimates for the difference between a single WAIS-R subtest and the mean of all subtests, and permits the clinician to determine whether the difference obtained by a particular examinee is statistically significant. PMID- 1458002 TI - Autism in Down's syndrome: presentation and diagnosis. AB - Although autism is said to occur rarely with Down's syndrome, it may be more common in those persons with Down's syndrome who also show superimposed behavioural problems. In this brief report, the authors explore this possibility. They describe three patients with Down's syndrome who were referred for behavioural reasons and were found to have coexisting autism. They propose that a systematic study of the association of these two conditions may have implications on research and clinical practice. PMID- 1458003 TI - Kallmann's syndrome and mental handicap. AB - A case of Kallmann's syndrome is reported in a 62-year-old mentally handicapped man with clinical and laboratory characteristics of the syndrome. The literature is reviewed and the possible associations with mental handicap explored. PMID- 1458004 TI - Auxological aspects of male and female puberty. PMID- 1458005 TI - The chronicle of growth hormone receptor deficiency (Laron syndrome). PMID- 1458006 TI - Clinical and biochemical characteristics of growth hormone receptor deficiency (Laron syndrome). PMID- 1458007 TI - Molecular biology of growth hormone receptor dysfunction. PMID- 1458008 TI - Point mutations in the growth hormone receptor gene of patients with Laron syndrome. PMID- 1458009 TI - Therapeutic use of insulin-like growth factor I: lessons from in vivo animal studies. PMID- 1458010 TI - Growth and growth hormone secretion at puberty: the role of gonadal steroid hormones. PMID- 1458011 TI - Pubertal growth in genetic disorders of sex hormone action and secretion. PMID- 1458012 TI - Myocyte cellular hypertrophy and hyperplasia in the heart during postnatal maturation and ageing. PMID- 1458013 TI - Growth hormone therapy in Turner's syndrome: an update on final height. Genentech National Cooperative Study Group. AB - The Genentech National Cooperative Study of growth hormone (GH) therapy in Turner's syndrome was initiated in 1983; 70 girls with Turner's syndrome were randomly assigned to observation or to treatment with GH alone, oxandrolone alone, or a combination of GH plus oxandrolone for a period of 12-24 months. After completion of this phase, patients receiving GH alone were continued on GH, while all other patients received the combination of GH plus oxandrolone. Data are currently available on the 62 girls who were treated for a minimum of 3-6 years. When compared with the height velocities anticipated for girls of comparable ages with untreated Turner's syndrome, both GH alone and a combination of GH plus oxandrolone resulted in an increase in height velocity, which was most prominent during the first 2 years of treatment and was sustained for at least 6 years. Although GH therapy is continuing at present in half of the patients, 14 of 17 girls (82%) receiving GH alone and 42 of 45 girls (93%) receiving combination therapy have exceeded their projected adult heights. For the 30 girls who have stopped therapy, the current mean height is 151.9 cm, compared with their original mean projected adult height of 143.8 cm. These results demonstrate that GH therapy can result in short-term (3-6 years) acceleration of growth, as well as in improved adult height. PMID- 1458014 TI - Effects of chronic growth hormone excess on cardiac contractility and myosin phenotype in the rat. AB - The effects of chronic growth hormone (GH) hypersecretion on intrinsic contractile properties of the myocardium were studied in rats bearing a GH secreting tumour. Body weight and heart weight increased, but no true cardiac hypertrophy was observed. The maximum active force of left ventricular papillary muscle was increased, and the maximum shortening velocity of the unloaded muscle was unaltered. This was despite a marked shift of the myosin isoforms towards the low ATPase activity V3 form, which was associated with a similar shift of myosin mRNAs. Total ATPase activity, measured on frozen sections, was unaltered suggesting, together with the results of the mechanical study, an increase in the number of active enzymatic sites. Studies performed on skinned fibres confirmed the increased myocardial contractility, thus suggesting that myocardial adaptation to chronic GH excess occurred, at least in part, at the level of the myofibrillar contractile apparatus. PMID- 1458015 TI - Cardiovascular effects of growth hormone--with special reference to growth hormone replacement therapy. PMID- 1458016 TI - Physiology of the fat cell, with emphasis on the role of growth hormone. PMID- 1458017 TI - Methods for determining fat mass and fat distribution. PMID- 1458018 TI - Hormonal effects on fat distribution and its relationship to health risk factors. PMID- 1458019 TI - Effects of growth hormone on fat mass and fat distribution. AB - GH has profound effects on the amount and distribution of adipose tissue. GHD in both children and adults is accompanied by an increased amount of adipose tissue and by the abdominal predominance of adipose tissue. In contrast, treatment with GH reduces adipose tissue, and redistributes adipose tissue from abdominal to peripheral depots. PMID- 1458020 TI - Effects of growth hormone on low-density lipoprotein metabolism. AB - GH appears to play an important role in mediating the increase in hepatic LDL receptor expression that occurs in response to pharmacological oestrogen treatment. Furthermore, in normal individuals there is evidence of an increased number of hepatic LDL receptors in response to GH, resulting in an accelerated elimination rate of the LDL particle and a subsequent lowering of LDL cholesterol. Further studies on lipoprotein metabolism in patients with GH deficiency, and also in patients with hypercholesterolaemia, would therefore be of interest. PMID- 1458021 TI - Genetic analysis of recombination in prokaryotes. AB - Bacteria provide a simple system for the genetic analysis of homologous recombination. More than twenty genes have been identified in Escherichia coli. The enzymatic activities associated with the products of many of these genes have been revealed by studies with model DNA substrates. It is now possible to pair homologous molecules in vitro and process these through defined intermediates into mature recombinants of the types predicted by genetic crosses. PMID- 1458022 TI - Interaction between bacteriophage lambda and its Escherichia coli host. AB - Bacteriophage lambda relies to a large extent on processes requiring interactions between viral- and host-encoded proteins for its lytic growth, establishment of lysogeny, and release from the prophage state. Both biochemical and genetic studies of these interactions have yielded new information about important host and lambda functions. In particular, mutations in Escherichia coli that compromise lambda DNA replication, genome packaging, transcription elongation, and site-specific recombination have led to the identification of bacterial genes whose products are chaperones, transcription factors, or DNA-binding proteins. PMID- 1458023 TI - Heat-shock proteins and stress tolerance in microorganisms. AB - Heat-shock proteins help microorganisms cope with the toxic effects of a wide variety of stresses. Some help the organism grow under moderately stressful conditions, others help it to survive more extreme conditions. Surprisingly, the relative importance of individual proteins differs between organisms. PMID- 1458024 TI - Flagella in prokaryotes and lower eukaryotes. AB - During the past year, significant advances have been made in the understanding of both prokaryotic and eukaryotic flagella. About 50 genes are dedicated to the assembly and operation of bacterial flagella. Recent discoveries have advanced our understanding of how these genes are regulated and how their products assemble into a functional, rotating organelle. The dynein arms of eukaryotic flagella are now also better understood. Several genes that are found in the mechanochemical macroassemblies have been cloned, and other loci have been identified, suggesting that there is even greater complexity than first expected. PMID- 1458025 TI - Movement of macromolecules between the cytoplasm and the nucleus in yeast. AB - Since the first description of signals for nuclear protein localization, studies with yeast have played an important role in our understanding of nuclear protein import. Very recent experiments suggest that new insights into the poorly understood process of RNA export will also emerge from analyses of yeast. Recent advances have facilitated our understanding of protein and RNA exchange between the nucleus and cytoplasm. PMID- 1458026 TI - Genetic analysis of photosynthesis in prokaryotes and lower eukaryotes. PMID- 1458027 TI - What is the minimum number of dedicated functions required for a basic cell cycle? AB - The genome of Escherichia coli has a coding capacity for about 4500 proteins but only a small number of these appear to be specific for the periodic events (initiation of DNA replication, chromosome partitioning and cell division) that punctuate the cell-duplication cycle: furthermore, many of these cell cycle dedicated functions are dispensible under certain conditions, although their presence undoubtedly increases the fitness of the organism to survive in a competitive environment. A simplified but effective cell replication cycle can probably operate with only a few cycle-dedicated proteins, in addition to those required for cell growth itself. PMID- 1458029 TI - Prokaryotes and lower eukaryotes. PMID- 1458028 TI - Sporulation in prokaryotes and lower eukaryotes. AB - During the past year, highlights in sporulation research include the demonstration that phosphorylation of SpoOA is a critical factor in Bacillus subtilis development; the identification of C alpha proteins, adenylyl cyclase and protein kinase A genes in Dictyostelium; proof that an endogenous antisense RNA regulates gene expression in Dictyostelium; and characterization of a second type of differentiated cell in Myxococcus. PMID- 1458030 TI - Freedom of speech--but only for the wealthy and powerful. PMID- 1458031 TI - Control, confront or collude: how family and society respond to excessive drinking. AB - Research on excessive drinking in the family context has revealed the range of ways of coping used by close relatives. Case material from ongoing research in England and Mexico is used to illustrate this point. This research is also revealing the ways in which the family, close and extended, often fail to support the coping actions of close relatives. The analogy is drawn between coping with excessive drinking in the family and coping in the work setting. In the latter context explicit alcohol policies have been developed. These often recommend combining confrontative and supportive coping. It may be difficult for relatives, in the family setting, to adopt such a policy without support. The forms of coping identified in family research and in work policies correspond to basic and universal dimensions of interpersonal behaviour: dominance-submissiveness and friendliness-hostility. These forms of responding to excessive drinking may be identified beyond the microsocial systems of family and workplace. They are evident, also, in the responses of community agents such as police and social workers, and at the level of local and national government. PMID- 1458032 TI - Severity of dependence and route of administration of heroin, cocaine and amphetamines. AB - This study investigates severity of dependence upon heroin, cocaine and amphetamines in a group of 200 heroin users, 75% of whom were not in contact with any treatment agency. For drug takers who were current users of more than one drug, heroin produced more severe dependence than either cocaine or amphetamine and many users of these stimulant drugs reported having experienced no problems of dependence. Severity of dependence was influenced by route of administration as well as type of drug. Heroin taken by injection was associated with more severe dependence than smoked heroin. For cocaine, injection and smoking were associated with equivalent dependence ratings, and both of these routes were associated with more severe dependence than cocaine used intranasally. For amphetamine, there were no differences in severity of dependence ratings for injection, intranasal or oral use. Severity of dependence was correlated with dose and duration of drug use; it was also associated with previous attendance at a drug treatment agency, though dependence problems were also common among heroin users who had never received treatment. Implications of these findings are discussed. PMID- 1458033 TI - Bromocriptine and cocaine cue reactivity in cocaine-dependent patients. AB - Based on previous reports that bromocriptine, a postsynaptic dopamine agonist, reduced cocaine craving and prevented relapse in cocaine-dependent subjects, effects of the drug were evaluated in 20 cocaine-dependent males in an inpatient drug rehabilitation programme. The subjective and physiologic effects of exposure to both cocaine-associated and neutral stimuli, presented using videotapes, were measured at one-week intervals. Between laboratory sessions subjects received either bromocriptine (1.25 mg bid) or a matched placebo, administered in double blind fashion. Compared with the neutral videotape, the cocaine videotape elicited both a greater desire to use cocaine and more symptoms associated with cocaine self-administration. These results support an appetitive conditioning model of cocaine effects. Bromocriptine, however, had no effect on the cocaine cue-associated reactivity, which declined over the 1-week interval in both treatment groups. Methodological differences among studies that have examined the effects of bromocriptine in cocaine-dependent subjects may explain the variable findings observed. PMID- 1458034 TI - HIV risk of transmission behaviour amongst HIV-infected prisoners and its correlates. AB - Thirty-eight from a total of 42 known HIV-positive prisoners in the Irish prison system voluntarily cooperated in a survey of psychological attitudes, knowledge of risk behaviour, intentions with respect to future risk behaviour, and actual past risk behaviour. Of this group, 65% reported that they had put others at risk of HIV, since they became aware of their own HIV+ status. Only 16% stated that they would definitely not share their drug-taking equipment in the future and 32% that they would always use a condom in sexual intercourse. In general, psychological and biographical variables were not strongly related to whether or not the respondents had put others at risk of HIV. Nor were there any significant differences in knowledge of at risk behaviour between those who had and those who had not put others at risk. However, there was some evidence for considerable independence between risk-taking behaviour in the sexual and in the drug-taking domains, in that risk-taking in one area was not highly predictive of risk-taking in the other. PMID- 1458035 TI - Adolescent drug sellers: trends, characteristics and profiles. AB - This study examines drug selling among representative samples of high school students in Ontario. It involves three approaches, (i) examining the trend in drug selling between 1983 and 1989, (ii) assessing differences between sellers and non-sellers on demographic characteristics, levels of alcohol and drug use, and problems, and (iii) drawing detailed profiles of drug seller types. Drug selling declined considerably between 1983 and 1989. Sellers were more likely to be males and to use alcohol and drugs more often than non-sellers. Sellers also had more alcohol and drug problems and engaged in more delinquent acts. Drug sellers who sold cannabis only were less frequent users of drugs, less likely to have drug problems, and were also delinquent. PMID- 1458036 TI - Unemployment and use of drug and alcohol among young people: a longitudinal study in the general population. AB - A prospective study of a representative sample of nearly 2000 young people aged 17-20 years was started in 1985. It was followed up twice, in 1987 and in 1989. The Central Bureau of Statistics in Norway was responsible for the data collection. Sixty-five per cent of the stratified sample (1985) participated in all the three surveys. The aim of this paper has been to explore the relationship between unemployment and the use of drugs and alcohol. The results show that unemployment does not appear to influence the consumption of alcohol. In a high consumption group, unemployment seems to lead to a decrease in alcohol consumption, though there was a clear tendency to increase use of cannabis. The results seem to indicate that there was no increase in use of alcohol or drugs in response to stress as a result of unemployment, though unemployment may lead to a stronger identification with or joining marginalized or deviant subcultures which in turn leads to an increased use of cannabis. PMID- 1458037 TI - Smoking: a special need? AB - The smoking behaviour of 665 children aged 12-15 years with special educational needs was compared with that of a control group of 842 children in mainstream education. Each child was interviewed using a structured questionnaire and reported smoking behaviour was validated against scores on a carbon monoxide monitor. We identified as the most at risk group children with emotional and behavioural disorders. They had the highest smoking rates and were the heaviest smokers. In contrast, children with learning difficulties had slightly lower smoking rates than those of the control. There were significant associations between the children's smoking behaviour and the smoking behaviour of siblings and 'other adults' in the household, belonging to single parent families, low self-esteem and large friendship groups. The reported smoking rates of the families of both groups of special needs children was found to be considerably higher than that in the control group or in the general population. PMID- 1458038 TI - Dying to be equal: women, alcohol, and cardiovascular disease. AB - This data note explores the relationship of gender, alcohol consumption and premature death from cardiovascular disease (MCVD). Data on the 8164 deaths attributed to MCVD from the National Mortality Followback Study (NMFS) were analyzed controlling for gender and consumption. Women who are heavy drinkers die young at a rate equal to that of men who drink heavily. In light of this, we recommend that future research and preventive efforts in this area include females as subjects and alcohol as a major risk factor. PMID- 1458039 TI - The effects of advertising restrictions on tobacco consumption. PMID- 1458040 TI - Parent educational attainment and adolescent cigarette smoking. AB - In a longitudinal design, this study examined psychosocial mediators of the effects of parental educational attainment on adolescent smoking acquisition and also examined whether smoking transition had different antecedents among adolescents from families of varying educational backgrounds. Parents' low educational attainment acted as a moderate to strong risk factor for the initial onset of smoking among middle school girls. Some of this effect was mediated by the higher smoking prevalence among both parents and friends of these adolescent girls, as well as by their lowered expectations for academic success. However, these variables only partially mediated the effect of parent education. There were few indications of differential antecedents of smoking acquisition among adolescents from less and more highly educated families. Implications for public health antismoking campaigns are discussed. PMID- 1458041 TI - Gender differences in depression and anxiety among alcoholics. AB - Recent research suggests that psychopathology, in particular depression and anxiety, differentially affects the substance abuse treatment response of men and women. This study explores the relationship between global psychopathology, depression, anxiety, and alcoholism treatment outcome. These variables were assessed in a sample of 507 (373 men; 134 women) substance abuse clients at intake and at a 6-month follow-up. With the exception of alcohol dependence, there were significant differences in the levels of alcohol problems, depression, anxiety, and global psychopathology for men and women at both intake and follow up. For the whole sample and for men, initial levels of alcohol problems and alcohol dependence were the best predictors of alcohol problems at follow-up. For women, the initial levels of alcohol dependence and a global measure of psychological functioning were predictive of outcome at follow-up. These findings are compared with past research, and suggestions for further investigation are proposed. PMID- 1458042 TI - Gender differences in the manifestations of problem drinking in a community sample. AB - A probability sample of 6,250 respondents in Ontario and Quebec was surveyed by telephone to determine the prevalence of problem drinking and its relationship to other psychiatric symptoms. The survey instrument included a psychiatric symptom inventory and questions relating to problem drinking that were adapted from the Diagnostic Interview Schedule. This survey found a rate of 7.1% for problem drinking which parallels other recent community surveys. Rates for men are approximately six times greater than for women. A significant proportion (18.5%) of problem drinkers have concurrent psychiatric impairment. The extent and nature of concurrent psychiatric impairment and disability differs significantly for men and women. PMID- 1458043 TI - Duration of bulimia nervosa and symptom progression: a retrospective analysis of treatment-seeking bulimics. AB - Severity of bulimia nervosa upon presentation for treatment may be influenced by duration and age of onset of bulimic behaviors. This hypothesis was investigated in a retrospective study by correlating duration of bulimia and age of onset with sets of variables measuring the primary symptoms and other psychopathology associated with bulimia nervosa. The experimental design was cross-sectional. The sample included 153 women who had been diagnosed with bulimia nervosa. Canonical correlations indicated that younger age of onset and longer duration were associated with more severe bulimic symptoms and increased body image distortion. Anorexic symptoms were reduced over time, however, and weight gain (at a rate of about 0.54 Kg [1.2 lbs] per year) was correlated with duration of bulimic behaviors. Also, older age of onset and longer duration were associated with increasing social introversion. These findings were interpreted as supportive of the hypothesis that younger age of onset and longer duration of bulimic behaviors are associated with more severe bulimia and general psychopathology. Though limited by the retrospective nature of the study, these results substantiate the need for longitudinal investigations of bulimia nervosa. PMID- 1458044 TI - Processes of change in smoking cessation: a cross-validation study in cardiac patients. AB - The processes of change associated with smoking cessation were examined for 213 smokers and recent exsmokers who were scheduled for cardiac catheterization and compared to the processes reported by a sample of 180 nonmedical smokers and exsmokers. Subjects were classified into one of three stages of change depending on their readiness to quit smoking: precontemplation, contemplation, and action. The cardiac sample employed the processes of change more frequently than the nonmedical sample in all stages, but the functional relationship between the stages and processes of change was generally similar for the two groups. The hierarchical structure of the processes of change also was similar for both groups. Differences between the two samples in the use of the processes of change are discussed. These results are the first to support the validity of the stages and processes-of-change model of smoking cessation in a population experiencing severe illness. PMID- 1458045 TI - Utility and evaluation of biochemical markers of alcohol consumption. AB - Biochemical markers of alcohol consumption have a variety of clinical and research applications. Currently available markers such as the serum gamma glutamyl transpeptidase (GGT), serum transaminases, and the mean corpuscular volume (MCV) lack sufficient sensitivity and specificity to be used for screening of alcoholism in ambulatory patients. However, these tests can be helpful in corroborating a clinical suspicion of alcoholism. A number of special laboratory markers of alcoholism recently have been developed which may have increased diagnostic accuracy. Promising potential markers include serum carbohydrate deficient transferrin (CDT), red blood cell acetaldehyde, and acetaldehyde adducts. The application of reliable and practical markers of alcohol consumption could lead to significant improvements in the treatment of alcoholism and in the assessment of clinical trials. PMID- 1458047 TI - Nagging and other drinking control efforts of spouses of uncooperative alcohol abusers: assessment and modification. AB - This article presents a conception of spouse drinking control and an approach to assessment and modification to reduce the customary drinking control efforts of spouses of alcohol abusers unmotivated to enter treatment. Modification of the nonalcoholic spouse's customary drinking control is offered as an important early step in helping to prepare him or her to become a positive rehabilitative influence. Based on its use in unilateral family therapy with 68 spouses of uncooperative alcohol abusers, procedural guidelines, criteria for use, and two case examples from a crossover experimental dyad are described. Also presented are clinical results illustrating the success of the program, benefits and conditions relating to its use, and areas of possible application. PMID- 1458046 TI - A randomized double-blind study of neuroelectric therapy in opiate and cocaine detoxification. AB - Prior research on the use of transcranial neuroelectric stimulation suggested that the application of low-amperage, low-frequency alternating current via surface electrodes placed in the mastoid region could relieve the physiological signs and subjective symptoms of withdrawal and craving during opiate detoxification. These effects were reported without gradual tapering of the opiate or the addition of other medications. To test the efficacy of one particular form of neuroelectric therapy (NET), a double-blind, randomized, placebo-controlled study was conducted comparing active NET and placebo NET in the treatment of withdrawal and stabilization of 18 opiate-dependent and 25 cocaine-dependent subjects. Scores on scales for measuring substance withdrawal and craving for each abused substance, as well as the multiple dimensions of mood, were compared for degree of difference across the 10 days of treatment. There was an overall completion rate of 88%, with both cocaine and opiate groups reporting a comfortable detoxification and substantial improvement over the course of a 12-day hospitalization. There was no significant difference between the active or placebo groups, suggesting that placebo was as effective as active NET in reducing drug withdrawal or craving during cocaine and opiate detoxification. However, all placebo patients received 0.2 mA of current, which may have provided a degree of active current. Suggestions are offered for future research. PMID- 1458048 TI - Patterns and predictors of simultaneous and concurrent use of alcohol, tobacco, marijuana, and hallucinogens in first-year college students. AB - Polydrug use produces important health and safety risks. Little research has examined whether multiple drugs are used simultaneously (at the same time or in close temporal sequence). Instead, researchers have assessed concurrent polydrug use (the use of multiple drugs within a given time period such as years or months). The research here examined patterns and predictors of both simultaneous and concurrent polydrug use in 575 first-year college students. Both concurrent and simultaneous polydrug use were common for alcohol, tobacco, and marijuana. The percentage of concurrent polydrug users who were also simultaneous polydrug users ranged from 82% to 93% across subgroups defined by gender and the use of a single drug. Male gender, high levels of sensation seeking, and frequent alcohol use predicted single-drug versus polydrug use status as well as simultaneous polydrug use. Patterns and predictors of simultaneous and concurrent polydrug use should be addressed in prevention research and preventative interventions. PMID- 1458049 TI - Brain casein kinase 2: affinity purification procedure using immobilized polyethylenimine. AB - A simplified procedure for casein kinase 2 purification from bovine brain is described. The purification procedure consists of two affinity chromatography steps, using heparin and polyethylenimine immobilized on a synthetic matrix (Toyopearl 650M). The adsorption and elution conditions for each column were optimized, resulting in a simple elution protocol for each column. A stable, highly purified casein kinase 2 preparation was obtained in 4 h using this procedure. Polyethylenimine was shown to stimulate the casein kinase 2 activity using exogeneous substrates (casein, calmodulin, MAP2, and tau) but not the enzyme's autophosphorylation activity. The polyethylenimine stimulation could be overcome by applying a mass excess of the casein kinase 2 inhibitor, heparin. PMID- 1458050 TI - Purification of recombinant chimeric B72.3 Fab' and F(ab')2 using streptococcal protein G. AB - Streptococcal protein G has been used extensively for the purification of antibodies using the interaction of the Fc region with protein G. Many antibodies also interact with protein G through a low-affinity binding site for the Fab region. The exploitation of this low-affinity interaction for the purification of Fab' fragments is described here. Chimeric mouse-human B72.3 Fab' and F(ab')2 fragments were expressed by CHO cells and purified from CHO cell supernatant using protein G-Sepharose. Since chimeric B72.3 Fab' bound weakly to the protein G-Sepharose it could be separated from F(ab')2 and eluted with a pH 7 wash whereas B72.3 F(ab')2 required elution at pH 2. Both Fab' and F(ab')2 were recovered with full immunoreactivity and could be further purified using gel filtration chromatography to greater than 99% purity. This method allows the simple purification of directly expressed Fab' or F(ab')2 fragments from CHO cell supernatant. PMID- 1458051 TI - Expression in Escherichia coli: purification and properties of the recombinant human general transcription factor rTFIIB. AB - The human class II transcription factor TFIIB (rTFIIB) was overexpressed in Escherichia coli using a T7 RNA polymerase expression system and further purified to apparent homogeneity. The purified rTFIIB is identical to the endogenous factor according to the following criteria: molecular weight, microsequencing and mass spectra studies, ability to recognize the stable preinitiation complex formed between TFIID and the adenovirus 2 major late TATA box as demonstrated by gel shift as well as by DNase I footprinting assays, and transcription activity. PMID- 1458052 TI - High-level expression and simplified purification of recombinant ricin A chain. AB - Ricin toxin is a glycoprotein which catalytically inactivates eukaryotic ribosomes by depurination of a single adenosine residue from the 28S ribosomal RNA. The enzymatic activity is present in the A chain of the toxin molecule, whereas the B chain contains two binding sites for galactose. Since it is highly potent in inhibiting protein synthesis, the A chain is used to prepare cytotoxic conjugates effective against tumor cells. Such chimeric proteins are highly selective and have a wide range of clinical applications. Extensive preclinical studies on these conjugates require large amounts of purified A chain. Native ricin A chain is heterogeneous, since plants produce a number of isoforms of ricin toxin. Purified, native preparations often contain two types of ricin A chain which differ in the extent of glycosylation. By cloning and expressing the gene of A chain, one could obtain homogeneous toxin molecules devoid of carbohydrates. In addition, structural changes in the toxin polypeptide could be introduced by in vitro mutagenesis, which can improve the pharmacological properties and antitumor activity. Earlier methods of expression strategies using Escherichia coli have yielded only moderate levels of expression. In the present study, the coding region of ricin A chain was cloned into pET3b, a high-level expression vector under the control of the T7 promoter. Recombinant ricin A chain produced by this construct has an additional 14 amino acid residues at the NH2 terminus. Subsequently, a NdeI site was created at the 5' end of the gene by oligonucleotide-directed mutagenesis. The modified fragment was then introduced into pET3b vector to produce toxin polypeptide identical to the native sequence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458053 TI - Bacterial expression, purification, and in vitro N-myristoylation of HIV-1 p17gag. AB - The coding region of the N-terminal 17-kDa portion of HIV-1 Pr55gag (p17gag) was cloned into the pET-3c expression vector and was used to overexpress HIV-1 p17gag in Escherichia coli. Induction of the transformed bacteria caused the accumulation of a 17-kDa polypeptide in the soluble cell fraction which was released by sonication in hypotonic nondetergent buffer. The 17-kDa polypeptide was purified by ammonium sulfate precipitation and successive chromatography on G 75 Sephadex, DEAE-Sephacel, and S-Sephadex. The final product was purified 12 fold with about a 16% recovery from the original soluble cell lysate and was judged to be 97+% pure by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Western blotting with two different antibodies confirmed the identify of the purified 17-kDa polypeptide as authentic p17gag. In the presence of myristoyl-CoA and bovine brain N-myristoyl-transferase, p17gag was quantitatively N-myristoylated in vitro with a pseudo-first-order rate constant of 4.7 +/- 1.0 x 10(-3) min-1, but with only about 3% of the catalytic efficiency of N-myristoylation of a 16-residue peptide homologous to the N-terminus of p17gag. The myristate group in the N-myristoylated p17gag was stable to treatment with detergent and hydroxylamine consistent with a covalent N-acyl-amide linkage. The N-myristoylglycyl linkage was confirmed by partial acid hydrolysis and identification of the p-nitrobenzylazlactone derivative of the resulting N myristoylglycine by high-performance liquid chromatography. PMID- 1458054 TI - Rapid screening of a large number of immobilized textile dyes for the purification of proteins: use of penicillin-binding protein 4 of Escherichia coli as a model enzyme. AB - A rapid method for screening the affinity of proteins to dye-modified resins is described. Performing the binding and elution of the protein extracts in a batch wise manner and eluting the bound proteins with SDS-PAGE denaturation buffer speed up the screening process and allow the analysis of large collections of dyes. Penicillin-binding protein 4 of Escherichia coli was used as a model enzyme to determine the influences of pH, metal ions, and ionic strength (0 to 500 mM NaCl) on its binding behavior using a collection of 98 dye-affinity resins. PMID- 1458055 TI - Copurification of RNA polymerase I and the glucocorticoid-regulated transcription factor IC. AB - A simple and rapid method to copurify RNA polymerase I and the glucocorticoid regulated transcription factor, TFIC, is described. This protocol results in 1262 fold purification and 15% total recovery of the enzyme and factors needed to support faithful transcription in vitro from cloned mouse rRNA gene (rDNA). Using this method, proteins involved in rDNA transcription were purified from exponentially growing lymphosarcoma P1798 cells as well as cells treated with 0.1 microM dexamethasone. A combination of transcription and reconstitution assays using G-free cassette-containing constructs and polyacrylamide gel electrophoretic analysis upon silver staining were used to detect TFIC activity as well as the characteristic TFIC polypeptides in control and dexamethasone treated cell extracts. Treatment of P1798 cells with 0.1 microM dexamethasone for 24 h results in an over 95% reduction of TFIC activity, but no significant differences in the amount of TFIC polypeptides in the final product purified from control and glucocorticoid-treated cells could be detected. Our data indicate that glucocorticoid regulation of transcription of rDNA is mediated via post translational modulation of the activity of TFIC. PMID- 1458056 TI - Tyrosine-ester sulfotransferase from rat liver: bacterial expression and identification. AB - A nucleotide sequence that had been proposed for, but not identified as, rat liver aryl sulfotransferase (EC 2.8.2.1) was prepared in an appropriate vector and transformed into Escherichia coli. The protein, expressed in large amounts, was not aryl sulfotransferase (EC 2.8.2.1) but rather tyrosine-ester sulfotransferase (EC 2.8.2.9), a sulfotransferase also active with phenols but having a much wider substrate range that includes hydroxylamines and esters of tyrosine. The recombinant tyrosine-ester sulfotransferase was identified by its unique substrate spectrum, by comparison with three peptides that were sequenced from homogeneous tyrosine-ester sulfotransferase isolated directly from rat liver, and by the specificity of antibody raised to the rat liver enzyme. Two isoforms were obtained, each of which was difficult to solubilize upon sonication of E. coli. Both forms were solubilized with a solution of polyols (glycerol and sucrose) and subsequently purified to homogeneity. PMID- 1458057 TI - Biotin derivatives of endothelin: utilization for affinity purification of endothelin receptor. AB - Three different types of biotinylated endothelin 1 (ET-1) derivatives, [Cys1] biotinylated ET-1, [Lys9]-biotinylated ET-1, and [Cys1][Lys9]-dibiotinylated ET 1, were obtained when the biotinylation reaction was carried out with sulfosuccinimidyl-6-(biotinamido)hexanoate in an aqueous solvent. The binding of [Lys9]-biotinylated ET-1 to the ET receptor was as efficient as that of natural ET-1, whereas the binding of either [Cys1]-biotinylated ET-1 or [Cys1][Lys9] dibiotinylated ET-1 was significantly reduced. When ET-1 was reacted with succinimidyl-6-(biotinamido)hexanoate in an organic solvent, ET-1 was exclusively modified at lysine 9. The ET receptor was then isolated from human placenta by affinity chromatography with [Lys9]-biotinylated ET-1 and avidin-agarose. The purified ET receptor was active in ET binding and was resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis into two polypeptides with apparent molecular masses of 45 and 35 kDa. The NH2-terminal amino acid sequence indicated that the two polypeptides were from an identical subtype of the ET receptor (ETB, the ligand-nonselective type). A signal peptide from Met1 to Gly26 was missing from the 45-kDa ETB, whereas 64 amino acids at the NH2 terminus were missing from the 35-kDa ETB due to proteolytic cleavage which occurred between Arg64 and Ser65. Indeed, incubation of purified ETB with endopeptidase Arg-C resulted in degradation of the 45-kDa ETB, giving rise to the 35-kDa species by a specific cleavage at Arg64. The 35-kDa ETB was active in binding to ET-1, indicating that the NH2-terminal 64-amino-acid residues are not essential for ligand binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458058 TI - High-level production and purification of Escherichia coli N-acetylneuraminic acid aldolase (EC 4.1.3.3). AB - The Escherichia coli gene which encodes N-acetylneuraminic acid aldolase was isolated by the polymerase chain reaction, cloned into the inducible expression vector pTTQ18, and overexpressed in E. coli. The high yield of aldolase was achieved through both optimum growth of cells and efficient expression of the aldolase gene (20-30% soluble cellular protein). The recombinant enzyme was purified to homogeneity with an activity of 1.2-2.2 U/mg, which compared favorably with that of commercial preparations of E. coli aldolase (1.1 U/mg) and Clostridium perfringens aldolase (0.4 U/mg). The cloning strategy, fermentation conditions, purification protocol, and activity assay are described. PMID- 1458059 TI - Sigma Theta Tau International contributes to research on women's health issues. PMID- 1458060 TI - Nursing doctoral programs in the United States. Nursing doctoral programs listed outside the United States. PMID- 1458062 TI - Nursing research centers and organizations. PMID- 1458061 TI - Reflections on research in nursing. PMID- 1458063 TI - Grateful Med: an easy to use information tool. PMID- 1458064 TI - Initiation of a research program from a Sigma Theta Tau funded project. PMID- 1458065 TI - A deep and serious commitment to infants. PMID- 1458066 TI - Research utilization awards, utilization versus dissemination? PMID- 1458067 TI - Beveridge after 50 years. PMID- 1458068 TI - Life insurance and HIV antibody testing. PMID- 1458069 TI - Skin lightening creams containing hydroquinone. PMID- 1458070 TI - The demand for ophthalmic services. PMID- 1458071 TI - Audit and research. PMID- 1458072 TI - Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis. AB - OBJECTIVES: To compare the tolerance, efficacy, and pharmacokinetics of amphotericin deoxycholate (Fungizone) prepared in a parenteral fat emulsion (Intralipid 20%) or glucose in HIV patients with candidiasis. DESIGN: Non-blind randomised controlled trial. SETTING: University hospital; tertiary clinical care. PATIENTS: 22 HIV positive patients with oral candidiasis. INTERVENTIONS: Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5% glucose (amphotericin-glucose) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion (amphotericin-fat emulsion). MAIN OUTCOME MEASURES: Clinical tolerance (fever, chills, sweats, nausea, arterial pressure, and pulse rate); biological tolerance (serum creatinine, electrolyte, and magnesium values); clinical score of candidiasis; and serum concentrations of amphotericin. RESULTS: 11 patients were enrolled in each group. All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment (n = 3) or severe chills (n = 2), or both. For patients completing the amphotericin glucose treatment creatine concentration increased by 42 mumol/l; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion. Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion. Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion. Oral candidiasis score was reduced similarly in both groups. Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose. CONCLUSIONS: Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion. Preparation is simple and cost effective. Its efficacy is similar to that of conventional amphotericin. PMID- 1458073 TI - Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture. AB - OBJECTIVE: To evaluate the contribution of specific nutritional deficiencies (as indicated by zinc; vitamin A, C, and E; albumin; and haemoglobin concentrations) to the risk of pressure sores. DESIGN: Observational cohort study. SETTING: St James's University Hospital, Leeds. SUBJECTS: 21 elderly patients presenting consecutively to the orthopaedic unit with femoral neck fracture. MAIN OUTCOME MEASURE: Full thickness epidermal break over a pressure bearing surface. RESULTS: 10 patients (48%) developed a pressure sore during their hospital stay. Indices of zinc status and concentrations of albumin, haemoglobin, and vitamins A and E were similar in patients who developed a pressure sore and those who did not. Mean leucocyte vitamin C concentration, however, was 6.3 (SD 2.2) micrograms/10(8) cells in patients who developed a pressure sore as compared with 12.8 (4.6) micrograms/10(8) cells in patients who did not. CONCLUSIONS: Low concentrations of leucocyte vitamin C appear to be associated with subsequent development of pressure sores in elderly patients with femoral neck fractures. PMID- 1458076 TI - Juniors' hours: is the end in sight? AB - The question of how to reduce junior doctors' hours has taxed the government and hospital managers for nearly two decades. Now regional task forces are being asked to get them down to a maximum of 83 a week by 1 April next year. From a comparison of the way in which two different task forces (Northern and North West Thames) have responded to the challenge it emerges that most units will probably meet the 83 hour deadline by making simple rationalisations. Meeting the next deadline--of a 72 hour maximum by December 1996--will, however, require radical restructuring of working patterns. PMID- 1458075 TI - Demand incidence and episode rates of ophthalmic disease in a defined urban population. AB - OBJECTIVES: To estimate demand incidence and episode rates of ophthalmic disease in a defined urban population over one year. DESIGN: Study of patients presenting with eye problems to general practice and eye casualty department. SETTING: General practice and ophthalmic services in west Nottingham. SUBJECTS: 36,018 people from the combined practice lists of 17 Nottingham general practitioners. MAIN OUTCOME MEASURES: Ophthalmic disorder, age and sex of patient, and where presented. RESULTS: 587 consultations were recorded for ophthalmic problems, 1771 with general practitioners and 816 with eye casualty. Most consultations to general practice were by females (1066 (60%)), whereas men aged 15-44 accounted for most work in eye casualty. These men commonly presented with trauma. Infective conjunctivitis, the commonest condition, had an episode rate of 13.5/1000 population/year. Demand incidence for cataracts was 1.9/1000 population/year. Demand incidence for chronic conditions increased with age. CONCLUSIONS: As the average age of the population increases demand for ophthalmic services will rise. Planning and provision of resources to meet this increased demand should be considered now. PMID- 1458074 TI - Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception. AB - OBJECTIVE: To compare the effectiveness and acceptability of three regimens of postcoital contraception. DESIGN: Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose. SETTING: Community family planning clinic. SUBJECTS: 616 consecutive women with regular cycles aged 16 to 45 years. MAIN OUTCOME MEASURES: Number of pregnancies, incidence of side effects, and timing of next period. RESULTS: The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group. CONCLUSIONS: Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed. PMID- 1458078 TI - Sexual harassment at work. PMID- 1458077 TI - US health care. III: The reform problem. PMID- 1458079 TI - ABC of monitoring drug therapy. Why monitor drug therapy? PMID- 1458080 TI - Euthanasia. PMID- 1458081 TI - Euthanasia. PMID- 1458082 TI - Euthanasia. PMID- 1458083 TI - Euthanasia. PMID- 1458084 TI - Euthanasia. PMID- 1458085 TI - Propofol infusion in children. PMID- 1458086 TI - Propofol infusion in children. PMID- 1458087 TI - Propofol infusion in children. PMID- 1458088 TI - Propofol infusion in children. PMID- 1458089 TI - King's College Hospital's A&E department. PMID- 1458090 TI - Partners in practice. PMID- 1458091 TI - Treating tuberculosis in developing countries. PMID- 1458092 TI - Reducing pain associated with injection of lidocaine. PMID- 1458093 TI - Dermatological causes of pruritus ani. PMID- 1458094 TI - Dermatological causes of pruritus ani. PMID- 1458095 TI - Osteoporosis in men. PMID- 1458096 TI - Faecal urge incontinence caused by exercise. PMID- 1458097 TI - Use of live donors in renal transplantation. PMID- 1458098 TI - Change in drug treatment after discharge from hospital. PMID- 1458099 TI - Human insulin and awareness of hypoglycaemia. PMID- 1458100 TI - Severity of imported falciparum malaria. PMID- 1458101 TI - Controlling deaths from volatile substance abuse. PMID- 1458102 TI - Assessment of patients over 75. PMID- 1458103 TI - John Loutit's advance in collecting blood. PMID- 1458104 TI - X-Y linkage and schizophrenia. PMID- 1458105 TI - Acne associated with inhaled glucocorticosteroids. PMID- 1458106 TI - Intracerebral haemorrhage after dermal nitrate application. PMID- 1458107 TI - Iron dextran and systemic lupus erythematosus. PMID- 1458108 TI - Are elderly people living alone an at risk group? AB - OBJECTIVE: To test the hypothesis that elderly people living alone are an at risk group with a high level of morbidity that makes high demands on health and social services. DESIGN: Secondary analysis of data from a community survey of 239 people aged 75 and over, identified from general practitioners' age-sex registers. SETTING: Nine practices in the London boroughs of Brent and Islington. MAIN OUTCOME MEASURES: Scores on the mini-mental state examination; stated satisfaction with life; assessment of mobility; numbers of diagnoses of major physical problems; numbers of prescribed drugs taken; urinary incontinence; alcohol consumption; contacts with general practitioners and hospital outpatient and inpatient services; contact with community health and social services. RESULTS: There were significantly more women among those living alone (93/120 (78%) v 63/119 (53%); p < 0.0005) and the median age of elderly people living alone was higher (81 v 80; p < 0.04). Those living alone and those living with others showed no significant differences in measures of cognitive impairment, numbers of major physical diagnoses, impaired mobility, or use of general practitioner or hospital services. Stated satisfaction with life was somewhat higher in those living alone. Elderly people living alone were significantly more likely to have contact with chiropody, home help, and meals on wheels services and less likely to have someone they could contact in an emergency or at night. Living alone increased the likelihood of contact with one or more community health professionals (district nurses, health visitors, or chiropodists) considered as a group and also increased the likelihood of contact with social services as a whole. There was a tendency for more of those living alone than those living with others to have home visits from their general practitioners, but there were no significant differences in contact with hospital services between the two groups. CONCLUSIONS: Elderly people living alone do not have an excess of morbidity compared with those living with others and do not seem to be an at risk group requiring specifically targeted assessments. More help is needed to provide elderly people living alone with a point of contact in case of emergency. PMID- 1458109 TI - Introduction of a partial shift system for house officers in a teaching hospital. AB - OBJECTIVES: (1) To introduce a partial shift system to reduce the hours of work of preregistration house surgeons to an average of 64 a week to comply with the New Deal for junior doctors; (2) to test linking the partial shift concept to an existing structure of "on call" firms. DESIGN: Formal assessment after three months of a pilot partial shift system for eight house surgeons on three firms instituted on 1 November 1991, followed by questionnaire and interview evaluation at three and six months of a revised system implemented on 1 February 1992. SETTING: Department of general surgery at St Bartholomew's Hospital, London. SUBJECTS: 24 house surgeons attached to three surgical firms. RESULTS: In eight weeks each house surgeon worked one week (five shifts) of night duty, one week of "cover" (afternoon and evening) duty, and six weeks of normal daytime hours. Each weekday a house surgeon from the firm on call worked an extended daytime on call shift until 10 pm. Weekend duties were split between two house surgeons from the firm on call. A computer generated graphical display of the rota was used to facilitate leave planning. Average working hours were reduced to below 64 per week, including prospective cover, without detriment to patient care and educational standards. Within the shift system individual house surgeons could be on call with their own firm by day and at weekends. Opinions were equally divided among junior staff as to their preference for either on call or partial shift systems. CONCLUSIONS: The principles of this partial shift system are generally applicable and the model can readily be adopted by district general hospitals. PMID- 1458110 TI - ABC of monitoring drug therapy. Patient compliance. PMID- 1458111 TI - Screening for abdominal aortic aneurysms. PMID- 1458112 TI - Screening for abdominal aortic aneurysms. PMID- 1458113 TI - Domiciliary thrombolysis by general practitioners. PMID- 1458114 TI - Domiciliary thrombolysis by general practitioners. PMID- 1458115 TI - Screening for abdominal aortic aneurysms. PMID- 1458116 TI - Domiciliary thrombolysis by general practitioners. PMID- 1458117 TI - Domiciliary thrombolysis by general practitioners. PMID- 1458118 TI - On site medical services at major incidents. PMID- 1458119 TI - UK major trauma outcome study. PMID- 1458120 TI - Vitamin K and childhood cancer. PMID- 1458121 TI - Vitamin K and childhood cancer. PMID- 1458122 TI - Antenatal screening for Down's syndrome. PMID- 1458123 TI - Antenatal screening for Down's syndrome. PMID- 1458124 TI - Antenatal screening for Down's syndrome. PMID- 1458125 TI - Simulation model for planning renal services. PMID- 1458126 TI - Simulation model for planning renal services. PMID- 1458127 TI - Heterosexual AIDS epidemic. PMID- 1458128 TI - Heterosexual AIDS epidemic. PMID- 1458129 TI - Tachycardia during cisapride treatment. PMID- 1458130 TI - Tachycardia during cisapride treatment. PMID- 1458131 TI - Measuring glycated haemoglobin. PMID- 1458132 TI - Measuring glycated haemoglobin. PMID- 1458133 TI - Thoracoscopic pericardiectomy. PMID- 1458134 TI - Specialist training. PMID- 1458135 TI - Specialist training. PMID- 1458136 TI - Specialist training. PMID- 1458137 TI - SI units still used in some American journals. PMID- 1458138 TI - Abortion in the first trimester. PMID- 1458139 TI - Abusing old people. PMID- 1458140 TI - Corticosteroids in advanced cancer. PMID- 1458141 TI - Pet birds and lung cancer. PMID- 1458142 TI - Mental health services for children. PMID- 1458143 TI - "Without work all life goes rotten". PMID- 1458144 TI - Comparison of enalapril and nifedipine in treating non-insulin dependent diabetes associated with hypertension: one year analysis. AB - OBJECTIVES: To compare the efficacy, safety, and tolerance of enalapril and nifedipine in hypertensive patients with non-insulin dependent diabetes. DESIGN: One year double blind follow up of patients randomly allocated to either enalapril or nifedipine with matching placebos for the alternative drug. SETTING: Metabolic Investigation Unit, Hong Kong. SUBJECTS: 102 patients were randomised: 52 to nifedipine and 50 to enalapril. At baseline 44 patients had normoalbuminuria, 36 microalbuminuria, and 22 macroalbuminuria. MAIN OUTCOME MEASURES: Blood pressure, albuminuria, and parameters of renal function and glycaemic control. RESULTS: In patients who completed one year's treatment the median dose required by the nifedipine group (n = 49) was 60 mg/day; seven (14%) required additional diuretics. Of 41 patients given enalapril, 37 required the maximum dose (40 mg/day) and 27 (76%) required diuretics. At one year mean arterial blood pressures were similar in both groups. Albuminuria fell by 54% in the enalapril group and 11% in the nifedipine group (p = 0.006). Fractional albumin clearance ratio fell by 47% in the enalapril group and increased by 3% in the nifedipine group (p = 0.009). Creatinine clearance fell similarly in both groups but plasma creatinine concentration was increased by 20% in the enalapril group versus 8% in the nifedipine group (p = 0.001). CONCLUSION: Patients taking enalapril often required diuretics to control blood pressure. Enalapril reduced proteinuria significantly more than nifedipine in the microalbuminuric and macroalbuminuric patients but increased plasma creatinine concentrations. Longer follow up is required to clarify the importance of enalapril's antiproteinuric effect. PMID- 1458145 TI - Pet birds as an independent risk factor for lung cancer: case-control study. AB - OBJECTIVE: To test the hypothesis that exposure to pet birds increases risk of developing lung cancer. DESIGN: Case-control study. Computerised interviews were used to assess previous exposure to pets and other risk factors for lung cancer. SETTING: Three major hospitals treating respiratory disease in former West Berlin. SUBJECTS: All people newly diagnosed as having primary malignant neoplasm of the trachea, bronchi, or lung who were 65 or younger and control subjects matched for age and sex from the general population of former West Berlin. 279 cases and 635 controls qualified for the study; 239 cases and 429 controls participated. MAIN OUTCOME MEASURES: Odds ratio of developing lung cancer according to whether or not pet birds were kept and the duration of keeping pet birds. RESULTS: In addition to the risk of lung cancer imposed by smoking, passive smoking, and occupational exposure to carcinogens, an increased relative risk of 2.14 (95% confidence interval 1.35 to 3.40) was found among people exposed to pet birds. The adjusted odds ratio for exposures longer than 10 years was 3.19 (1.48 to 8.21). CONCLUSIONS: Avian exposure seems to carry a risk of lung cancer. Until the pathogenesis is understood, long term exposure to pet birds in living areas should be avoided, especially among people at high risk of developing lung cancer. PMID- 1458146 TI - Avian exposure and bronchogenic carcinoma. AB - OBJECTIVE: To investigate the association between bird keeping and risk of lung cancer. DESIGN: Case-control study asking detailed questions on exposure to domestic birds and other pets, smoking, and various demographic and potentially confounding variables. SETTING: District general hospital; current admissions interviewed in hospital or recent admissions interviewed at home. PATIENTS: 143 patients with lung cancer, 143 controls with heart disease, and 143 controls with orthopaedic conditions individually matched for age, sex, date of admission, and current or past admission. MAIN OUTCOME MEASURES: Odds ratios for lung cancer in relation to various aspects of bird keeping, after adjustment for smoking and other relevant confounding variables. RESULTS: Risk of lung cancer was not significantly associated with household exposure to pet birds at any time or at various specific periods in life, or to keeping large numbers of birds. For specific types of birds no association was seen for living in households with budgerigars or canaries but risk was significantly associated with keeping pigeons (odds ratio 3.53, 95% confidence interval 1.56 to 7.98). This remained significant after regression analysis to account for confounding variables (3.9, 1.2 to 12.62) in both sexes and all age groups. CONCLUSION: Bird keeping may confer some risk of lung cancer but the relation is not as strong as previously reported. PMID- 1458147 TI - The TAPS project. 16: Difficult to place, long term psychiatric patients: risk factors for failure to resettle long stay patients in community facilities. AB - OBJECTIVE: To identify patients who could not be resettled in the community as part of the closure plans of two psychiatric hospitals and to determine their numbers and risk factors for failure. DESIGN AND SETTING: Prospective study of the closure of Friern and Claybury psychiatric hospitals. PATIENTS: The first third (369) of long stay psychiatric patients to be resettled. OUTCOME MEASURES: Reasons for patients being readmitted to hospital and not leaving the patients' service needs. RESULTS: 22--6% of both hospitals' long stay patients--were not successfully resettled in the community. Eighteen continuing care places per 100,000 of catchment area population seem to be required for this group. Patients whose placements were unsuccessful were usually readmitted because of a deterioration of their mental state and aggressive behaviour, both of which persisted and necessitated their continuing stay in hospital, often in a locked ward. Risk factors associated with failure were a high level of psychosis; a diagnosis of paranoid psychosis; incontinence; and being male. But having a social network, especially a large one, seemed to aid successful placement in the community. CONCLUSION: Rehabilitation efforts should be focused on the characteristics of these patients that put them at risk of failing to succeed in community placements. PMID- 1458148 TI - The TAPS project. 17: Readmission to hospital for long term psychiatric patients after discharge to the community. AB - OBJECTIVE: To identify risk factors which increase the likelihood of readmission for long stay psychiatric patients after discharge from hospital. DESIGN: Follow up for five years of all long stay patients discharged from two large psychiatric hospitals to compare patients readmitted and not readmitted. SETTING: Friern and Claybury Hospitals in north London and their surrounding catchment areas. Most patients were discharged to staffed or unstaffed group homes. SUBJECTS: 357 psychiatric patients who had been in hospital for over one year, of whom 118 were "new" long stay and 239 "old" long stay patients. MAIN OUTCOME MEASURES: Readmission to hospital and length of subsequent stay. RESULTS: Of all discharged patients 97 (27%) were readmitted at some time during the follow up period, 57 (16%) in the first year after discharge, and 31 (9%) then remained in hospital for over a year. The best explanatory factors for readmission were: male sex, younger age group, high number of previous admissions, higher levels of symptomatic and social behavioural disturbance, a diagnosis of manic-depressive psychosis, and living in a non-staffed group home. CONCLUSIONS: During the closure of psychiatric hospitals, facilities need to be preserved for acute relapses among long term, and especially younger, discharged patients. Staffed group homes may help prevent relapse and reduce the number of admission beds required. PMID- 1458149 TI - Elder abuse in Britain. PMID- 1458150 TI - Steroids in advanced cancer: survey of current practice. PMID- 1458151 TI - [A comparative study of the psychotropic activity of different salts of homopantothenic acid]. AB - Psychotropic activity of different salts of homopantothenic acid was studied. In homopantothenic acid derivatives, the substitution of calcium ions by sodium and magnesium ions gives rise to a decrease of the sedative and potentiation of the stimulating properties. PMID- 1458152 TI - [Changes in the narrow-band components of the EEG spectrum under the action of nootropic drugs]. AB - Patients with asthenic disorders were examined for EEG reactions to the administration of some nootropics. The significance of the narrow bands of the post-drug EEG spectrum was revealed. According to these data, the detailed EEG profiles of the nootropics under study were obtained. Analysis of these EEG profiles discovered the common and specific characteristics of different nootropics. PMID- 1458153 TI - [The prolonged use of calcium antagonists in myocardial infarct in rats: their effect on hemodynamics and the contractile function and morphology of the heart muscle]. AB - Experiments on rats with myocardial infarction induced by occlusion of the left coronary artery were made to explore the influence of calcium antagonists injected intraperitoneally for a long time (daily, for 21 days) on hemodynamics, contractile function and morphology of the heart muscle. It has been shown that verapamil (0.5 mg/kg), diltiazem (2 mg/kg) and nimodipine (20 micrograms/kg) do not exert under those conditions any noticeable effect on pump and contractile heart functions. Administration of verapamil in a doze of 2 mg/kg enhanced heart failure. The drugs under study normalized the response of contractile heart function to volumetric load, which is related to a considerable measure to the acceleration of reparative processes in the myocardium. PMID- 1458154 TI - [The characteristics of the action of mildronate (dihydrate 3-(2,2,2 trimethylhydrazine)propionate) on the red blood parameters in heart failure]. AB - Mildronat potentiates the therapeutic effect of the combined treatment of heart failure, which includes the use of nitro drugs. It also decreases the level of methemoglobin in the patients' blood and improves the phosphate balance, especially that of 2,3-diphosphoglycerate to control oxygen transport by hemoglobin, which is of paramount importance in hypoxia caused by coronary heart disease. PMID- 1458155 TI - [The cytotoxicity of strophanthin G and digoxin]. AB - Cytotoxicity of strophanthin G and digoxin was studied in experiments on lymphoid cells and carcinoma of cervix uteri cells. The glycosides inhibited the growth of three strains of cultured tumor cells tested. It has been found that highly toxic doses of the drugs produced no changes in the cell multiplication of normal human fibroblasts. PMID- 1458156 TI - [The effect of grofollon on the induction of sex maturation in female rats]. AB - The authors provide the results of experimental studies carried out in immature female rats given the gonadotropin grofollon to stimulate puberty. Grofollon was administered in doses of 20, 30 or 50 units. It was dissolved in a physiological solution or prolongon. The effect of grofollon was found to depend on the dose and type of the solvent. The earliest response (in 6 hours) to grofollon administration was marked by an increase of plasma estradiol. 24 hours after the hormonal treatment there was a rise of the mass of the ovaries and uterus, in particular. The vagina opened on the 3d day. The dissolution of grofollon in prolongon was discovered to enhance the drug efficacy. PMID- 1458157 TI - [The effect of L-carnitine and acetyl-L-carnitine on blood serum lipid peroxidation in vitro]. AB - In the action mode of carnitine derivatives, the leading role is played by lipid transport inside the cell. Bearing in mind the important role of lipid peroxidation in lipid metabolism in the body and broad-range indications for use of carnitine derivatives in medical practice, it was decided to investigate the influence of carnitine derivatives on lipid peroxidation (LPO) in vitro to have a better understanding of the action mode of these drugs, as carnitine, according to the reported data, may affect certain LPO parameters in vivo. PMID- 1458158 TI - [The effect of isonitrozine on gas homeostasis]. AB - The action of the cholinesterase reactivator isonitrosine on gas homeostasis was studied in experiments on intact dogs. It has been found that oxygen consumption and CO2 release by tissues were enhanced within the period from 15 min to 6 days following isonitrosine administration. Simultaneously, oxygen return by the blood was improved. Such action of isonitrosine was unrelated to its effect on the cholinesterase activity of red blood cells. PMID- 1458159 TI - [The antioxidizing activity of malonic acid derivatives]. AB - Nine newly synthesized malonic acid derivatives were shown to have antioxidizing activity which makes up from 30 to 60% of the antioxidizing activity of ionol and vitamin E in vitro and does not yield to the activity of the latter substances in vivo. It is suggested that malonic acid derivatives may influence the antioxidizing enzymes--catalase, glucose-6-phosphate dehydrogenase and superoxide dismutase. PMID- 1458160 TI - [The effect of verapamil and nifedipine on cholesterol esterification and accumulation in macrophages]. AB - Administration of verapamil and nifedipine in doses of 10-75 microM into the culture of mouse peritoneal macrophages incubated in a non-lipid medium with acetylated low density lipoproteins (50 g protein/ml) decreased the incorporation of 14C oleate into cholesterol esters by 50-90%, increased the content of intracellular free cholesterol by 19-79% and did not influence the content of total cholesterol in macrophages. Administration of verapamil and nifedipine in doses of 25 and 50 microM in the culture of macrophages previously enriched with cholesterol reduced the rate of cholesterol esterification by 22-62%. After combined administration of verapamil and nifedipine in doses of 25 microM into the medium the rate of cholesterol esterification in macrophages fell by 72.4%. PMID- 1458161 TI - [The effect of protease tissue inhibitor on the activity of pancreatic proteolytic enzymes in in-vitro experiments]. AB - The authors provide the data on in vitro experimental studies into the pharmacological properties of protease inhibitor obtained from bovine pancreas. It is shown that the preparation exerts an inhibitory action on pancreatic proteolytic enzymes such as trypsin, kallikrein, and elastase, drastically reduces the total proteolytic activity in pancreatic tissue homogenates. Comparison with the protease inhibitor gordox has demonstrated the inhibitory effect of both preparations to be practically similar. PMID- 1458162 TI - [The mechanism of the antioxidant action of D-penicillamine]. AB - The mechanism of the antioxidative effect of D-penicillamine was studied under the conditions of NADPH- and CCl4-dependent lipid peroxidation in microsomes of rat liver and adrenalin autooxidation reaction. The antioxidative action of the drug was shown to be due to both its chelating properties and direct anti-radical influence. The chelating effect was more pronounced and depended on the concentration of ferric ions in the medium. PMID- 1458163 TI - [An experimental validation of the combined use of dimephosphon with nonsteroidal anti-inflammatory preparations]. AB - The effects of dimephosphon combined with nonsteroidal anti-inflammatory drugs were studied in rats and mice with experimental inflammation. The influence of dimephosphon on ulcerogenic activity of these drugs was also investigated. The dependence of the combinations efficiency on the scheme of dimephosphon administration was established. Synergism in anti-inflammatory activity between dimephosphon and ortophen (sodium diclofenac), indomethacin, and acetylsalicylic acid was shown. The possibility of decreasing the ulcerogenic effects of the drugs by dimephosphon was established. The effects of dimephosphon combinations are discussed as the basis for their use in clinical practice. PMID- 1458164 TI - [The pharmacokinetics of the prolonged-action beta-adrenoblocker nadolol in hypertension patients after a single administration]. AB - The pharmacokinetics of the beta-adrenoceptor blocker nadolol was studied in 30 patients suffering from mild hypertension given a single 80 mg dose of the drug. It has been shown that distribution of the pharmacokinetic parameters in this sample can be assumed normal. Their averages are similar to the reported data on healthy subjects. The mean retention time of nadolol in the body was estimated for the first time. The absorption of the drug was shown to be slow, which together with a low degree of bioavailability, may be associated with its low lipophility. A close correlation was demonstrated between the half-life and the mean absorption time estimates computed from blood serum and nadolol excretion with urine. The conclusion is made that glomerular filtration plays the key role in the drug elimination. PMID- 1458165 TI - [The effect of clofelin on the carotid sinus and cardiopulmonary baroreceptor reflexes in man]. AB - A study was made of the influence of clophilin on the vasomotor component of the sinocarotid and cardiopulmonary baroreflexes of man. Clophilin was shown to intensify the cardiochronotropic component of the sinocarotid reflex, thereby suppressing blood pressure fall, evoked by activation of carotid sinus mechanoreceptors, and producing no effect on vasoconstriction induced by a decrease of pressure in the right atrium. It is concluded that the mechanism of the hypotensive effect of clophilin is not related to modulation of the baroreceptor reflexes from the regions of high and low pressures. PMID- 1458166 TI - [The correction of the hepatotoxicity of antitubercular preparations with tocopherol acetate and riboxin]. AB - It has been established in experiments on white rats that prolonged (for 2 weeks) intoxication with antituberculous drugs (isoniazid plus rifampicin plus pyrazinamide) results in cytolytic liver injury. This manifests by hyperaminotransferasemia, initiation of lipid peroxidation, suppression of the antioxidant system and bile production. Daily injections of tocopherol acetate (15 mg/kg) and riboxine (100 mg/kg) together with administration of antituberculous drugs reduce their hepatotoxicity. The combined use of these hepatoprotectors and antioxidants provides a dramatic increase of their efficacy in durable intoxication with antituberculous drugs. PMID- 1458167 TI - [An analysis of acute poisonings with drugs]. AB - Analysis of acute drug poisonings was made using materials available at the Saint Petersburg Toxicological Center for the period of 10 years. The indicated poisonings became two times more frequent and in 1989 accounted for 76% of the total number of intoxications. Poisonings with tranquilizers ranked first in frequency, then followed antihistamine drugs, neuroleptics and hypnotics. There was an increase in the percentage of hemiton poisonings, which turned out lethal in 1.6-3% of cases. In most cases, the drugs were taken to commit suicide, more rarely they were used to have or to potentiate the effects of alcoholic euphoria. Among women, poisonings were encountered three times more often than among men. PMID- 1458168 TI - [The selectivity and protective properties of m-cholinolytics in dichlorodivinylphosphate poisoning]. AB - The activity of selective and nonselective muscarinic antagonists was examined in different experimental models. According to the results obtained, the protective effect of muscarinic antagonists during acute dichlordivinyl phosphate (DDVP) poisoning depends on the M1-subtype cholinoreceptor blockade. Meanwhile the efficiency of muscarinic antagonists in inhibition of tremor reaction induced by arecoline administration is associated with interaction between the drugs and the M2-subtype. The blocking of presynaptic M2-cholinoreceptors is likely to cause the decrease of protective potency of muscarinic antagonists in acute DDVP poisoning. PMID- 1458169 TI - [The experimental treatment of cyanide poisoning with a methemoglobin solution]. AB - The stroma-free methemoglobin solution proved to be an effective antidote against acute cyanide poisoning in experiment. The poisoning was induced by intraperitoneal administration to rats of cyanide solutions in doses of 5, 10 and 15 mg/kg. Methemoglobin solutions were injected intravenously in doses of 2 and 4 g/kg. All the rats given methemoglobin solution after the administration of cyanide survived. Spectrophotometry of rat urine demonstrated rapid excretion of methemoglobin cyanide. PMID- 1458170 TI - [A spectral analysis of the effect of adapromine on brain bioelectrical activity]. AB - A study was made of the influence of adapromine on bioelectrical activity of the brain, sensorimotor cortex, dorsal hippocamp and lateral hypothalamus in freely moving wakeful rats. Adapromine was established to evoke a decrease of the amplitude of the dominant peak and dominant theta-activity in power spectra of the EEG in the cortex and hippocamp, with an increase of rapid wave activity in the beta 2 range in the right cortex and hippocamp. These changes attained maximum after 1 to 1.5 hour and lasted up to 4-5 hours after adapromine administration. These changes can be viewed as activation of the cortex and hippocamp, which may attest to the presence of antidepressive and psychostimulant effects in the action spectrum of adapromine. The specific influence of adapromine on catecholaminergic processes of the brain may lie at the basis of the above effects. PMID- 1458171 TI - [An experimental study of the hepatoprotective properties of phytoecdysteroids and nerobol in carbon tetrachloride-induced liver lesion]. AB - The phytoecdisteroids ecdisterone, turkesterone and cyasterone were administered in a dose of 5 mg/kg per os to rats with hepatitis induced by subcutaneous injections of CCl4. Similarly to the anabolic drug nerobol (10 mg/kg), the above agents not only interfere with the manifestation of the hepatic action of CCl4 (in this case the effect of the phytoecdisteroids is more remarkable) but also favour a more rapid normalization, as compared to the control, of functional and metabolic disorders in the liver. The phytoecdisteroids and nerobol noticeably stimulate the recovery of bile secretion, the synthesis of bilirubin and bile acids, cholesterol excretion. PMID- 1458172 TI - [The effect of GABA-ergic agents on the blood electrolyte balance in acute craniocerebral trauma]. AB - A study was made of the balance of potassium and sodium ions in red blood cells and blood plasma of rats with acute craniocerebral injury seen over time. It has been established that phenibut (50 mg/kg) and sodium hydroxybutyrate (0.2 g/kg) prevent electrolytic changes in blood at different periods of injury. The K+/Na+ ratio of red blood cells can be used as an objective indicator to characterize the time course of changes in craniocerebral injury and to evaluate the efficiency of its pharmacological correction. PMID- 1458173 TI - [The antihypoxic and radioprotective properties of selective adenosine receptor agonists]. AB - The selective A1- and A2-receptor agonists L-PIA (ED50 = 0.55-0.78 mmole/kg) and NEGA (D50 = 0.05-0.1 mmole/kg) possess high antihypoxic and radioprotective effects. A2-subtype receptors may be involved in the antihypoxic and radioprotective effects of adenosine analogs. PMID- 1458174 TI - [The kinetic characteristics of drugs in the presence of perfluorocarbon blood substitutes]. PMID- 1458175 TI - [The mechanisms of the ethomersol correction of postischemic hypoperfusion]. AB - In rat experiments during brain ischemia (30-min carotid artery occlusion), ethomersol administered intraperitoneally in a dose of 50 mg/kg before occlusion or at the end of ischemia eliminated postischemic hypoperfusion. The effect of the drug was due to its spasmolytic and antiaggregatory activities. An analysis of the vasodilating action of ethomersol revealed its capacity to block potential dependent calcium channels and partially intracellular calcium mobilization when the adrenergic and serotoninergic receptors were activated. The antiaggregatory activity of the drug appeared as inhibited platelet aggregation, which was induced by ADP, serotonin, arachidonic acid, thrombin, and as enhanced antiaggregatory activity of the vascular wall. PMID- 1458176 TI - [A comparative evaluation of the cardioprotective and antianginal actions of energy-providing agents]. AB - The limitation of a myocardial necrotic area by some energy-yielding compounds in rat coronary occlusion and their capacity to elevate the ischemia threshold in conscious rabbits were studied. Sodium malate, ascorbic acid and phosphoenolpyruvate were demonstrated to reduce the sizes of necrotic areas and increase the ischemia threshold, whereas cytochrome C and fructose-1,6 diphosphate were effective solely in limiting the infection area. It was concluded that the preventive antianginal effect of energy-yielding and electron accepting compounds depended on their capacity to accumulate in intact cardiomyocytes. PMID- 1458177 TI - [The efficacy of hepatoprotectors and cytochrome P-450 inducers in correcting the functional activity of the hepatocyte microsomal system in an acute lesion of the liver in prepuberty]. AB - Intragastric CCl4 inhibited the activity of and lowered the levels of the major components of the hepatic monoohygenase enzyme system in one-month rats. Benzonal was found to be more effective in correcting the impaired monooxygenase enzyme system of hepatic cells in immature rats with acute hepatitis than silibor, phytin and zyxorin. PMID- 1458178 TI - [The effect of hepatoprotectors on the functional activity of rat hepatocyte mitochondria in in-vitro and in-vivo systems]. AB - In in vitro experiments essential, flacumin, and silibor inhibited the respiratory activity of isolated mitochondria and failed to affect the respiration of hepatocytes in rats at condition 4 by Chance. Essential uncoupled mitochondrial oxidative phosphorylation in the in vitro system. The hepatoprotectors used in ethanol-induced abnormality restored the activity of mitochondrial oxidative phosphorylation of hepatocytes to its level in intact animals. PMID- 1458179 TI - [The mechanism of action of the bioflavonoid lespeflan and the antihypoxant TB-4 on nitrogen metabolism in animals with acute kidney failure]. AB - The changes in the levels of urea and creatinine caused by the new native preparation lespeflanum and the antihypoxant TB-4 were studied in animal experiments. The agents tested produced a significant hypoazotemic effect in acute renal failure. Lespeflanum showed diuretic and natriuretic effects in healthy animals, elevated plasma aldosterone levels and decreased hepatic arginase activity. There was a normalization of thioldisulfide metabolism in patients treated with lespeflanum and TB-4. The hypoazotemic effect of lespeflanum was due both to its anabolic and anticatabolic effects. Lespeflanum is recommended for wide clinical application to treat patients with chronic renal failure. PMID- 1458180 TI - [The effect of clofelin on uterine contractile activity (experimental and clinical research)]. AB - Pregnant rat experiments have revealed a pronounced and prolonged naloxone irreversible depriming effect of clofelin, 0.05 and 0.5 mg/kg, on the frequency and amplitude of myometrial biopotentials, which was eliminated with phenoxybenzamine. In clinical testing, clofelin in therapeutical doses showed a marked tocolytic effect in threatened abortion at 18-34-week gestation. The agent in the same doses normalized blood pressure in hypertensive pregnants, without having a negative action on the fetus. PMID- 1458181 TI - [The enhanced efficacy of the pharmacological regulation of the processes of blood cell activation and interaction in the flow by polymer additives decreasing the hydrodynamic resistance of the blood]. AB - The increase of blood cell auto- and interactivation and the decrease of aspirin antiaggregant effect were demonstrated under hemodynamic conditions of a stenotic zone in a model maximally approached to the real blood circulation. The lowering of platelet activation, of the release of active agents from platelets, and of platelet-leukocyte interactivation was attained under the conditions of the flow modified by the drag-reducing polymer solution. The recovery of aspirin antiaggregant activity and aspirin-induced reduction of the total platelet release of platelet- and leukocyte-activating agents were demonstrated under the influence of the polymer. PMID- 1458182 TI - [The mechanism of the prevention by ethomersol of disorders in erythrocyte deformability in cerebral ischemia and recirculation]. PMID- 1458183 TI - [The antithromboxane activity of alpha- and omega-modified carbocyclic analogs of PGH1]. AB - In in vitro experiments on a model of arachidonate- and thrombin-induced platelet aggregation, analogues of PG endoperoxides displayed an antiaggregatory effect or stimulated spontaneous platelet aggregation in the whole blood of man and rabbits, but a slight antiaggregatory effect in the rabbit intact organism. The presence of the hydroxyl group instead of the routine alkyl omega-chain produced an antiaggregatory effect due to TxA2 receptor blockade. PMID- 1458184 TI - [The action of carnitine-series preparations in experimental alloxan diabetes mellitus]. AB - The study was undertaken to examine the effects of l-carnitine and acetyl-l carnitine in rats and mice with experimental alloxan diabetes. The findings suggest that acetyl-l-carnitine is more effective against diabetes in increasing glucose tolerance, restoring the impaired response of glucagon to glucose, showing glycogen-sparing action than is l-carnitine. PMID- 1458185 TI - [The possible participation of the GABA metabolic system in the mechanisms of the protective action of L-aspartate in hypoxia in an enclosed space]. AB - L-Aspartate given intradermally in a dose of 100 mg.kg-1 to mice 2-3 minutes before placement to a hypoxic chamber was shown to prolong the mean animal lifespan by 38% and to delay hypoxic convulsions by 38-40%. The agent was ascertained to maintain the higher glutamate decarboxylase (GD) activity and GABA levels in the brain during hypoxia and prevent GD activity and GABA levels from their drastic diminution when hypoxic convulsions occurred. PMID- 1458186 TI - [A comparative study of the activity of antihypoxic agents in hemic hypoxia]. AB - Amino derivatives of ortho-benzoquinone (OBQ) were demonstrated to have a protective action in acute toxic hemic hypoxia induced by sodium nitrite given to laboratory animals. This action of OBQ was due to its capacity to activate the recovery of blood oxygen transport function by accelerating the restoration of methemoglobin and determined by their electron-acceptor properties, lipophilicity and NADP-dependent methemoglobin reductase affinity. PMID- 1458187 TI - [The pharmacological regulation of inflammation: the current problems and developmental outlook]. AB - The papers summarizes the latest data on the pathogenesis of an inflammation reaction, with emphasis on the mechanism of action of antiinflammatory agents, including the drug regulation of the arachidonic acid cascade, and on the mechanisms of unassociated action on prostaglandins. It also discusses the prospects for using the existing antiphlogistics and the main trends in designing the new approaches to the pharmacological regulation of inflammation. PMID- 1458188 TI - [The influence of modulators of enzyme activity on the pharmacological effect of thiopental sodium and ketamine and on the pharmacokinetics of thiopental sodium]. AB - The rat experiments studied the impact of inductors and inhibitors of enzymatic activity of xenobiotic metabolism on the pharmacological activity of sodium thiopental and ketamine and on the pharmacokinetics of sodium thiopental. Cocarboxylase, cobalt chloride and cimetidine enhanced the pharmacological action of sodium thiopental, but failed to exert any action on the effect of ketamine. The preparations of vitamin K, particularly vikasol and menadione sodium bisulfite, and phenobarbital attenuated the effects of these anesthetics, but tocopherol unchanged it. Phenobarbital and vikasol accelerated blood elimination of sodium thiopental, whereas cimetidine and cocarboxylase slowed down this process. PMID- 1458189 TI - [The radioprotective and antioxidant properties of solubilized alpha-tocopherol acetate]. AB - A single intravenous administration of solubilized alpha-tocopherol acetate in a dose of 1 mg/kg to CBA x C57Bl x F1 male mice 3 and 24 hours before radiation was demonstrated to increase 30-day survival rates in the animals. Oily alpha tocopherol acetate had the identical effects when the agent was intramuscularly given in a dose of 10 mg/kg. There was a rise in peripheral leukocyte counts 0.5 hour after solubilized alpha-tocopherol acetate administration. The antioxidative activity of the solubilized agent was 3.3 times as high as that the routine agent when attacking Tween 80. The higher radioprotective activity of solubilized alpha tocopherol acetate is accounted for by its enhanced bioavailability, antioxidative activity and effects on the factors of nonspecific body's resistance. PMID- 1458190 TI - [The interaction of the immune system and the liver mono-oxygenase system]. AB - The effect of different immunostimulants (prodigiosan, levamisole, T-activin, sodium diethyl dithiocarbamate, sodium nucleinate, lithium chloride, muramil dipeptide, B-activin) and mixed hepatic function oxidase inhibitors (cimetidine, chloramphenicol) or inducers (phenobarbital, flumecinol, rifampicin) on immune reactivity (macrophage function, humoral and cellular responses) and hepatic microsomal function (hexobarbital sleeping-time) was studied in non-inbred and BALB/c male mice. There was a high correlation between the ability of immunostimulants to depress hexobarbital metabolism and their ability to enhance macrophage activity (carbon clearance test), but not humoral and cellular immunity. No reciprocal changes occurred in immune reactivity after positive or negative pharmacological modulation of hepatic drug metabolizing enzyme activity. PMID- 1458191 TI - [The pharmacological correction of recurrent immediate-type allergic reactions]. AB - The effect of drugs on the early and late phases of repeated allergic reactions (RAR) was studied in experiments on rabbits. The action of the drugs was estimated by the number of challenge doses of antigen, endured by survived and dead rabbits, percentage of the animals' death, and by the place of each group on the lethality scale. Diphenhydramine, ouabain and their combinations, silver nitrate (20 mg/kg) and DOCA enhanced whereas histamine, unithiol, cholesterol, and silver nitrate (20 and 0.2 mg/kg) decreased allergization in the period of RAR. The characteristic features of the action of the drugs on RAR were revealed and compared to the first allergic reaction. Qualitative and quantitative differences were shown in the action of different drug doses and combinations on RAR. The authors provide evidence for the possibility of treating allergic diseases by drug administration in a quiet period. PMID- 1458192 TI - [The inhibiting effect of 8-Cl-adenosine-3',5'-cyclophosphate on the growth of melanoma B-16 in mice]. AB - A site-selective analogue of the cyclic adenosine monophosphate 8-chloro adenosine-3',5'-cyclophosphate was studied for its effects on the growth of transplanted murine melanoma B-16. When the agent was given to the mice, a substantial effect on the growth of the tumor was produced by a number of factors, which included the route of administration, concentration of the agent, the time and duration of therapy. Intraperitoneal injections of the agent in a dose of 20 mg/kg/day which were made during three consecutive days, beginning from day 5 after tumor transplantation caused a 58% decrease in tumor growth as compared to the controls. An examination of tumour biopsy specimen revealed that after a course of the injections there was a significant suppression of the activity of cAMP-dependent protein kinase, type I, and a drastic increase in that of cAMP-dependent protein kinase, type II. PMID- 1458193 TI - [The polymorphism of pachycarpine oxidation]. AB - The ratio of urinary excretory pachycarpine to its oxidized metabolites, 2- and 5 dehydropachycarpines (metabolic ratio) was determined in a selective group of 81 unrelated cardiac patients from a Moscow Caucasian population given pachycarpine in a dose of 25 g. The metabolic ratio distribution was shown to be bimodal. Ninety five per cent of the patients had the metabolic ratio lower than 28 while 4 (5%) patients higher than 70. In 25 patients of the group, the pachycarpine metabolic ratio was evaluated after quinidine, 50 mg. Twenty-two patients with a relatively low metabolic ratio showed a dramatic (several times) increase, while in 3 patients with the prior metabolic ratio higher than 70, the effect of quinidine was insignificant. The findings suggest that pachycarpine oxidation is genetically polymorphic and similar to the polymorphism of sparteine/debrisoquine oxidation. Pachycarpine may be used as a marker in phenotyping the population. PMID- 1458194 TI - [The role of ketone bodies in the development of postalcoholic-intoxication heart damage in rats]. AB - Experiments on rats subjected to forced alcoholization for 5.5 days were made to measure the content of ethanol, acetaldehyde and ketone bodies in the blood during intoxication and 2 days after ethanol withdrawal and to estimate the intensity of postintoxication disorders in heart activity on the third day after alcoholization withdrawal. A positive correlation was discovered between depression of left ventricular contractility and the blood content of acetaldehyde and ketone bodies. The magnitude of the threshold of heart fibrillation did not correlate well with the concentration of ethanol during alcoholization. However, it agreed well with ethanol concentration in the postintoxication period. Additional administration to the animals of beta hydroxybutyrate or caprylic acid in the postintoxication period intensified heart contractility depression. The conclusion is drawn that elimination of ketosis in ethanol withdrawal as well as a progressive taking out of alcoholic patients from dipsomania can prevent the development or attenuate the intensity of postintoxication heart injury. PMID- 1458195 TI - [A morphological assessment of the efficacy of benzofurocaine in experimental burns]. AB - Studies of the effect of benzophurocaine on the morphological structure of the skin and viscera in animals with burn disease have shown the drug to have a protective action. The latter one manifested itself in a considerable reduction of injuries to the viscera and in a more rapid recovery of the disordered structure and function. PMID- 1458196 TI - [A comparative pharmacological evaluation of sea buckthorn, rose and plantain oils in experimental eye burns]. AB - Hippophae, Rosa and plantain oils have been shown to produce and essential therapeutic action on chemical burns of rabbit eye. The effect was attained in the phases of trophic disturbances and epithelialization. PMID- 1458197 TI - [The chronobiological approach--a way to enhance the efficacy of pharmacotherapy in neurology and psychiatry]. PMID- 1458198 TI - [Dimethyl sulfoxide in experimental and clinical medicine. The achievements and prospects]. PMID- 1458199 TI - [The choice of the preparation in the drug therapy of arrhythmias]. PMID- 1458200 TI - Ultrasonic study of processed milk cream and vegetable oils. AB - Food systems are complex and inhomogeneous in nature. Ultrasonic propagation velocity in the food systems, in this case processed milk cream and vegetable oils, is studied. Ultrasonic properties of the food systems are similar to those of complex biological tissues. The presence of vegetable oil as an adulterant in the processed milk cream is detected with the help of a double-probe-through transmission ultrasonic technique. The present study helps to maintain quality control of various food systems, particularly with regard to their adulteration, if any. PMID- 1458201 TI - High frequency pressure propagation in viscoelastic tubes: a new experimental approach. AB - A new method for estimating the high-frequency characteristics of wave propagation (phase velocity and attenuation per wavelength) in hydraulic lines is presented in this work. It consists of measuring the ratio of pressure amplitudes at two distinct sections of an occluded tube at different frequencies, and minimizing the difference between the experimental pattern and the theoretical one predicted on the basis of the transmission line theory. In this work the method is used for estimating the high frequency propagation characteristics of two different latex tubes. The values obtained are then compared with those provided by the more traditional three-point pressure method. The results of our trials demonstrate that the new method furnishes reliable estimations of the asymptotic values of phase velocity and attenuation per wavelength, provided the frequencies used during the experiment are sufficiently high. Moreover, the method turns out quite robust as to the influence of noise and possible measurement errors. For this reason it seems particularly suitable for studying wave propagation under difficult experimental conditions, such as those met with when measurements are performed on blood vessels in vivo. Finally, some discrepancies between our experimental results and the predictions of the transmission line theory are pointed out, and their possible origin examined. PMID- 1458202 TI - A study of fracture and inelastic behavior of bioactive glass-ceramics and glasses. AB - The fracture and inelastic behavior of A-W glass-ceramics, phosphate glasses, silicate glasses, and borate glasses were determined in simulated body fluid (SBF), kerosene, and water. By using the stable crack growth technique, an inelastic behavior was observed on the diagram of load versus load-point displacement. From these studies, it was suggested that the inelastic behavior of bioactive glass-ceramics was produced by the plastic deformation of glassy phase on the grain boundary. PMID- 1458203 TI - Computer simulation on creep of amalgam in Class I cavity. AB - The creep behavior of amalgam in Class I cavity was simulated by an axi-symmetric elastic creep finite element method. In this procedure, the stress and time dependencies of the creep strain of amalgam were incorporated. Exponents of stress and time dependencies were postulated as 2.0 and 1.0, respectively. Amalgam with 1.0% of creep value (tested by American Dental Association Specification No. 1) were selected for the material to calculate. Simulation was conducted for the occlusal force of 40, 100, and 150 N, respectively, on the caps of enamel and vertical direction to the axis of the tooth. Results show that creep strain of amalgam in the cavity did not increase linearly with time because the amalgam deformed to become stress-free and creep rate was a function of the stress. It was concluded that elastic deformation of the crown with no filling material in its cavity is an important factor in determining the creep strain and the gap between the cavity and the restorative material. PMID- 1458204 TI - Literature survey on biomedical applications of thermography. AB - Thermography is a noninvasive technique through which temperatures are monitored and recorded, thereby allowing visualization of heat flow. There are three types of thermography: liquid crystal thermography (LCT), infrared thermography (IRT) and microwave thermography (MWT). This paper presents a survey of the literature pertinent to the biomedical applications of these types of thermography. The noninvasive and high resolution characteristics of the thermographic systems make them valuable diagnostic as well as therapeutic aids. Typical research areas include detection of blood flow, diagnosis of joint inflammation and cancer, thermal modeling of various body parts, and use in reproductive problems. The survey discloses that thermography has found applications in various fields in medicine, veterinary medicine, pharmacy, and dentistry. PMID- 1458205 TI - Comparison of the electrochemical properties of various orthopedic porous metals. AB - The electrochemical properties of various porous metal coatings used in reconstructive orthopedic prosthetics were examined. Potentiodynamic corrosion testing was used to evaluate the behavior of the following porous metals; CSTi on Cast CoCr, CSTi on Ti-6Al-4V, CoCr beads on Cast CoCr, CoCr beads on Ti-6Al-4V, CP Ti beads on Cast CoCr, and CP Ti beads on Ti-6Al-4V. Analysis of the resultant corrosion scans showed that these materials behave similarly to one another. No corrosion-related anomalies were noted. PMID- 1458206 TI - Flexibilized gelatin film-based artificial skin model: I. Preparation and properties of the films. AB - A method was developed to prepare a simple, flexibilized gelatin film-based artificial skin model. The films are tough, adhere to open wounds spontaneously, are permeable to body fluids, and can release incorporated bioactive compounds over 4-5 days. PMID- 1458207 TI - Flexibilized gelatin film-based artificial skin model: II. Release kinetics of incorporated bioactive molecules. AB - Any delivery system for bioactive molecules should have the ability to release the compound in question in a reproducible and predictable way over a certain period. For artificial skin models that are designed to enhance healing by the use of growth factors, this requirement poses another problem: the design of a delivery method that can provide a realistic assessment of the release kinetics. This means that the design should "mimic" conditions encountered in an open wound, i.e., only a certain part of the film can face the wound, from which it can absorb wound fluid that will dissolve the incorporated bioactive molecule and bring it to the open wound. Such a system has been developed and the release of 125I-labelled insulin, incorporated into flexibilized gelatin films, has been determined. The details of this study follow. PMID- 1458208 TI - An experimental study on biomechanical properties of hepatic tissue using a new measuring method. AB - Hepatic tissue is an important internal organ for life. In this paper, we combined the moire method (an optical method) and indentation technique to investigate biomechanical response of hepatic tissue. To examine this measuring technique, we first measured the biomechanical properties of the block of pig's hepatic tissue using this method. The experimental result indicated that the pig's hepatic tissue was obviously a viscoelastic material. We closely analyzed the change of curves for force relaxation, creep, and nonlinear deformation of the block of pig's liver. Meanwhile, we also compared the changes in the biomechanical parameters of normal and cirrhosis hepatic tissue of humans. PMID- 1458209 TI - Sonomicrometric studies on the effects of long-term pumping of cardiac assist device on the bulk and regional mechanics of the normal left ventricle in goat. AB - Pneumatically driven, diaphragm type left ventricular assist devices (LVADs) were implanted into 2 goats with normal hearts for approximately 1 month to study the effects of long-term pumping of LVAD on the cardiac mechanics. One sham-operated goat was used to obtain control data. Diameters and myocardial segment lengths of the left ventricle were measured with an ultrasonic displacement meter to calculate the bulk mechanical work (BMW) and regional myocardial mechanical work (RMW), respectively. The LVAD was pumped in the 2:1 drive mode (one counterpulsated pumping in every two cardiac cycles), and was temporarily driven in the 1:1 mode (one pumping in every cardiac cycle) or stopped to obtain the data under these conditions. During the second half of the post-operative period while the animal condition was stable, the BMW in the 2:1 and 1:1 modes were approximately 59% and 72% of that observed under the temporary pump-off condition (0.22 W/(100 g)), respectively. The RMW in the 2:1 and 1:1 modes were 69% and 74% of that obtained during pump-off (6.2 mW/cm3), respectively. The myocyte diameter in the subendocardial layer was reduced by unloading effect of 1-month pumping, whereas those in middle and subepicardial layer showed little change. PMID- 1458210 TI - Wave propagation in the silicon tube: comparison of the two-point and three-point pressure methods. AB - The values of the propagation coefficient measured on a silicon rubber tube in the frequency range 1-15 Hz were compared, using four different equations. The first formula is based on three simultaneous pressure measurements performed at equidistant points; the remaining three equations are original, and make use of only two of the three pressure measurements together with a no-flow condition at the terminal tube section. The results of our trials demonstrate that the experimental phase velocity, obtained with all equations, settles at a value about 25% in excess of the theoretical one computed with a classic linear mathematical model. This result may be explained by an increase in the dynamical Young modulus with respect to that measured in static conditions. However, the three-point method introduces great errors in the results in the frequency range 11-14 Hz where the spectrum of the second signal becomes minimum. In all cases, the experimental value of attenuation per wavelength at mid-high frequencies is greater than the theoretical one valid for a purely elastic tube. The attenuation values obtained with the two-point method can be explained by introducing a small contribution of wall viscoelasticity (2-3 degrees) into the linear model. Attenuation per wavelength computed with the three-point methods turns out about threefold that computed with each of the two-point formulas. This result supports the idea that the accuracy of the three-point method may be insufficient to achieve correct estimation of wave attenuation, especially when the distance between transducers is small compared to wavelength. PMID- 1458211 TI - Greater incidence of electrocardiographic left ventricular hypertrophy in black men than in white men in Evans County, Georgia. AB - Population-based studies of black populations in the United States and Puerto Rico have reported higher prevalences of electrocardiographic left ventricular hypertrophy compared to white or lighter-skinned populations residing in the same areas. This study examines the incidence and correlates of electrocardiographic left ventricular hypertrophy in a population-based, biracial cohort of 435 white and 163 black men from the Evans County, Georgia, Heart Study, who were examined at entry in 1960 and reexamined in 1967. Only men over 35 years of age who were free of cardiovascular disease and had normal electrocardiograms at entry were eligible. Black men had a nearly fourfold greater incidence of electrocardiographic left ventricular hypertrophy compared to white men (13.5% vs 3.7%, respectively; incidence ratio 3.7; 95% CI 3.2-4.4). After statistically adjusting for age, systolic blood pressure, weight, and the change in weight and blood pressure, black men had a threefold greater incidence of electrocardiographic left ventricular hypertrophy compared to white men (logistic odds ratio 3.0; 95% CI 1.6-6.1). In summary, black men showed a significantly greater risk of developing electrocardiographic left ventricular hypertrophy at 7 year follow-up in Evans County compared to their white counterparts. This elevated risk could not be explained by the independent or joint effects of risks factors for electrocardiographic left ventricular hypertrophy. PMID- 1458212 TI - Differences in neonatal mortality by race, income, and prenatal care. AB - To determine the extent to which the social and physical environment affects the association between prenatal care and black pregnancy outcome in Chicago, we performed a stratified analysis of 1982-1983 Illinois vital records and 1980 United States census income data. Median family income of the mother's census tract was used as the ecologic variable. In very-low-income census tracts (less than $10,000 per year), 40% of blacks and 47% of whites received adequate prenatal care. There was no racial disparity in the percentage of low-birth weight infants attributed to inadequate prenatal care among poor mothers. For mothers who resided in moderate-income areas ($20,001 to $30,000 per year), 50% of blacks and 67% of whites received adequate prenatal care. Although adequate (compared to inadequate) prenatal care was associated with improved birthweight distribution independent of community income, only in moderate-income areas was it related to black neonatal survival. For term black infants who received adequate prenatal care, residence in impoverished areas was associated with a nearly fourfold greater neonatal mortality rate (deaths per 1000 live births): 5/1000 vs 1/1000; RR = 3.8 (1.3-11.0). We conclude that place of residence is an important risk factor for black neonatal mortality. PMID- 1458213 TI - Renin-angiotensin-aldosterone system and thromboxane A2/prostacyclin in normotensive and hypertensive black Zimbabweans. AB - Fourteen normotensive and 14 hypertensive black men with mild essential low-renin hypertension were examined during two protocols producing sodium depletion (less than 40 mmol sodium diet per day) for 5 days, followed by sodium loading (300 mmol sodium diet per day) for another 5 days. Changes in plasma renin activity, urinary aldosterone excretion, and excretion rates of stable breakdown products of thromboxane A2 (thromboxane B2) and prostacyclin (6-keto PGF1 alpha) were simultaneously assessed by radioimmunoassay. On the basis of low-renin status and paradoxically normal aldosterone excretion in both normotensives and hypertensives, thromboxane B2 excretion was increased by 14% (not significant); 6 keto PGF1 alpha was significantly decreased by 47% in the hypertensives compared to the normotensives. As a result, thromboxane B2/6-keto PGF1 alpha ratio was significantly increased from 1.29 +/- 0.10 in the normotensives to 2.78 +/- 0.12 in the hypertensive patients. The same ratio increased significantly after sodium loading in both groups, but more distinctly in the hypertensives (40%). Prostacyclin is a vasodilator, a natriuretic, and a potent inhibitor of platelet aggregation. Thromboxane A2 has opposite effects. The impaired prostacyclin biosynthesis we found in the hypertensive patients could account for the increased vascular resistance and some complications typical for hypertensive state. PMID- 1458214 TI - Distributions of hemostatic variables in blacks and whites: population reference values from the Atherosclerosis Risk in Communities (ARIC) Study. AB - The Atherosclerosis Risk in Communities Study measured hemostatic variables in nearly 16,000 men and women, aged 45 to 64 years, from four US communities. This report, based on the first 12,681 participants, presents distributions of fibrinogen concentration, factor VII activity, factor VIII activity, von Willebrand factor antigen, protein C antigen, antithrombin III activity, and activated partial thromboplastin time. Many of the hemostatic variables differed between blacks and whites, and by sex and age. For example, compared to whites, blacks had higher mean values of fibrinogen, factor VIII, von Willebrand factor, and antithrombin III, and lower mean values of protein C. Some seasonal fluctuations in hemostatic variables were noted; most notably, mean values of factor VII were lowest and protein C were highest in subjects examined in the summer compared to those examined during the other seasons. These results provide population-based reference values on blacks and whites for those interested in the relation of hemostasis to disease. PMID- 1458215 TI - Race, stage of disease, and survival with cervical cancer. AB - Significant disparities in survival with cervical cancer were observed according to social and disease characteristics of 3711 patients from Connecticut from 1984 through 1988. Women with advanced disease were 25 times more likely to die during a 4-year follow-up than those diagnosed with carcinoma in situ. Elevated risk of death was also noted for blacks (OR = 1.73; 95% CI = 1.2-2.5) and for women diagnosed after the age of 52 years (OR = 33.4; 95% CI = 16.5-69.9). Persons living in census tracts with large proportions of high school graduates or with high median incomes experienced decreased risk (OR = 0.66; 95% CI = 0.45-0.98 and OR = 0.65; 95% CI = 0.44-0.95, respectively). Multivariate logistic regression analysis found the effects of stage of disease on vital status to be reduced by approximately 50% when adjusted for other factors, reflecting the sizable effect of a woman's background on those variables. Nonwhite and older women were at significantly greater risk of being diagnosed with invasive disease. PMID- 1458216 TI - Blood pressure in the South Pacific: the impact of social change. PMID- 1458217 TI - Ethnic variations in the chronic pain experience. AB - Although ethnic identity has been found to have an important influence on experimental and acute pain intensity and response, little work has been directed to understanding how ethnicity affects the chronic pain experience. We report the results of a quantitative study of 372 chronic pain patients, in six ethnic groups, who were under treatment at a multidisciplinary pain management center in New England. The study used questionnaires and standardized instruments for assessing pain intensity to determine whether ethnic background was significantly related to interethnic or intraethnic group variation in pain intensity and response when other significant medical, sociodemographic, and psychological variables were controlled. In this study population, the most frequent statistically significant intergroup differences in pain intensity and in behavioral, psychological, and attitudinal responses to pain are related to differences in ethnic identity and psychological coping style according to locus of control. In addition, in this population, ethnic identity is a predictor of locus-of-control coping style. The major statistically significant intragroup differences in pain intensity and response are related to differences in generation, degree of heritage consistency, and locus-of-control style. We suggest that treatment programs for multiethnic populations should include a thorough cultural assessment and that providers need to be aware of the potential effect of ethnic background on chronic pain patients' communications, concerns, and coping styles related to the chronic pain experience. PMID- 1458218 TI - Electrocardiographic left ventricular hypertrophy: what do we measure? PMID- 1458219 TI - The effect of ethnic origin on the rate of spontaneous late mid-trimester abortion. AB - The effect of ethnic origin on perinatal outcome is well recognized. An effect on the rate of spontaneous abortion has not been previously documented, to our knowledge. We report the results of a retrospective survey of late mid-trimester abortions (20 to 26 weeks gestation) at Dudley Road Hospital, Birmingham, England. The aims of the study were to document the rate of spontaneous late mid trimester abortion by ethnic origin and to define any differences in these groups, both medically and as a result of histological examination of the abortus, that might account for observed differences. Over an 18-month period, during which 6508 infants beyond 26 weeks gestation were delivered, 30 late mid trimester spontaneous abortions occurred (13 black, 10 white, 7 Asian). Abortion rates per 1000 deliveries were 12.9 for blacks, 3.6 for whites, and 2.7 for Asians. The differences between ethnic groups were statistically significant (chi 2 = 17.4; P = .0002). The black women experiencing spontaneous mid-trimester abortion were of higher mean parity and were more likely to have undergone a previous therapeutic termination. Review of pathology reports revealed more cases of chorioamnionitis and fetal pneumonia in this group. Although these results should be interpreted with caution, a relationship clearly exists between ethnic origin and late mid-trimester loss. Further study is warranted to establish the cause. PMID- 1458221 TI - The impact of molecular biology on the diagnosis and treatment of hemoglobin disorders. PMID- 1458220 TI - Primary health care in Senegal: lessons learned. PMID- 1458222 TI - The molecular genetics of Down syndrome. AB - Major advances have occurred in the understanding of the genetics of DS since the discovery a little more than 30 years ago that it resulted from an extra copy of HSA-21. It has been learned that only a small region of HSA-21 is required in triplicate to produce at least some of the DS phenotype. Future work will clarify which regions are responsible for particular phenotypes of interest. The mechanisms by which extra genetic material leads to phenotypic abnormalities in DS and other aneuploidies appear to be complex. Although gene dosage effects are operative for many loci, they do not appear to be strictly operative for all genes. A more thorough understanding of the effects of aneuploidy on gene expression is needed. To understand adequately the mechanisms by which extra genetic material leads to particular phenotypic features will require the use of animal models. The trisomy 16 mouse, as well as new transgenic and partial trisomic mouse lines currently being developed, may be of particular help in this endeavor. PMID- 1458223 TI - Mammalian X chromosome inactivation. PMID- 1458224 TI - Molecular analysis of mutation in the human gene for hypoxanthine phosphoribosyltransferase. PMID- 1458225 TI - Regulatory genes of human immunodeficiency viruses. PMID- 1458226 TI - The fragile X syndrome. PMID- 1458227 TI - Quality improvement: evolution or revolution. PMID- 1458228 TI - Indicators: will yours pass a survey? PMID- 1458229 TI - Our hospital uses a point system for medication errors. PMID- 1458230 TI - Monitoring readmissions to ICU. PMID- 1458231 TI - Visual techniques to report data. PMID- 1458232 TI - Three data sources beyond the chart. PMID- 1458233 TI - Prioritizing aspects of care. PMID- 1458234 TI - Using the PDCA cycle. PMID- 1458235 TI - Quality education: the Beloit Memorial Hospital experience. PMID- 1458236 TI - Groups: chaos or collaboration? PMID- 1458237 TI - Moving toward 1994--Part 2: Techniques of QI. PMID- 1458238 TI - Communicating quality information. PMID- 1458239 TI - Cause-and-effect diagrams. PMID- 1458241 TI - Making fun a part of quality. PMID- 1458240 TI - Employee involvement in the health care industry. PMID- 1458242 TI - Difficulties with the 10 steps. PMID- 1458243 TI - Promoting the development of hospitalized children. PMID- 1458244 TI - Action-oriented report forms. PMID- 1458245 TI - Shouldn't we punish personnel after repeated medication errors? PMID- 1458246 TI - Spreadsheets. PMID- 1458247 TI - Preoperative evaluation of the patient for regional anesthesia. AB - The preoperative evaluation of the surgical patient is important for optimizing the anesthetic management. The evaluation process for the regional anesthesia candidate is reviewed. Patient selection, a review of organ systems, and the impact of medications and selected diseases are also discussed. PMID- 1458248 TI - Current regional anesthesia techniques of the brachial plexus: 1992. PMID- 1458249 TI - Complications of continuous spinal anesthesia. AB - The increased use of continuous spinal anesthesia (CSA) in recent years has resulted in research efforts directed at reducing the complications associated with the technique. Complications of CSA are categorized as general, the same as those associated with single-shot spinal anesthesia, and specific, those associated solely with CSA. General complications include infection, backache, hematoma, and neurological sequelae. Specific complications are all related to catheter use. The risk of developing the neurological complication of postdural puncture headache (PDPH) led to the use of microcatheters designed specifically for CSA. While the incidence of PDPH decreased with the use of microcatheters, the risk of developing the more serious complication of cauda equina syndrome increased, resulting in a Safety Alert being issued by the Food and Drug Administration. PMID- 1458250 TI - Epidural blockade: a multifaceted anesthesia tool. AB - The search for an optimal analgesic and route of administration continues. The development of the epidural route of administration of local anesthetic solutions and opioids approaches this ideal. In this article, the author details why epidural blockade is a multifaceted anesthetic technique useful in obstetrics, surgery, and pain therapy. PMID- 1458251 TI - Beneficial effects of the combined techniques of caudal and general anesthesia in the pediatric patient: two case reports. AB - The practice of combining a caudal anesthetic with a general anesthetic is frequently used in the management of pediatric patients. The principal advantage is improved postoperative pain management. Additionally, the perioperative reduction of inhalation agents as well as narcotic and non-narcotic analgesics provides a faster, more pleasant recovery from anesthesia that may result in a shorter hospital stay. The addition of caudally administered narcotics provides superior postoperative pain management in the pediatric patient requiring prolonged hospitalization. This article examines this combined technique in two pediatric patients: one, an ambulatory patient, the second, a patient requiring a postoperative intensive care admission. PMID- 1458252 TI - Use of the peripheral nerve stimulator and standard, unsheathed needles in performing regional nerve blocks. AB - Although the use of peripheral nerve stimulators and unsheathed needles in performing nerve blocks has been previously described, there has been a growing emphasis on the use of specific, expensive equipment to ensure success. The availability of equipment designed for use in peripheral nerve blocks, insulated needles and nerve stimulators, will help promote the use of these techniques, but the expense of purchasing this specialized equipment may contribute to a decline in performance of certain types of blocks. This article reviews the use of standard equipment, available in most anesthesia departments, for performing peripheral nerve blocks successfully. PMID- 1458253 TI - Sedation and analgesia techniques for regional anesthesia. AB - The use of adjuvant drugs for regional anesthesia may be indicated for a variety of reasons. Some general patient considerations, indications for the commonly used sedatives and analgesics, and administration techniques for these agents for patients having regional anesthesia are discussed. PMID- 1458254 TI - An interesting postanesthesia case was presented. PMID- 1458255 TI - Anesthetic drug interactions. PMID- 1458256 TI - [Epidemiology of endemic non-venereal treponematoses]. AB - The occurring resurgence of endemic treponematoses warrant the renewal of WHO mass campaigns. These various infections, pinta, yaws, bejel and endemic syphilis, are due to a treponema apparently identical to the venereal syphilis one. These different treponematoses do act upon epidemiology of venereal syphilis. The recent outbreak of treponematoses justify the current researches in the development of a treponemal vaccine. PMID- 1458257 TI - Elucidation of kidney function by micropuncture: an historical perspective. AB - An understanding of the fundamental mechanisms of kidney function awaited the advent of micropuncture techniques. The initial micropuncture study by Wearn and Richards in 1924 presented the first direct evidence that the initial step in urine formation was the process of ultrafiltration at the glomerulus and that certain solutes were reabsorbed in the renal tubules. Subsequent micropuncture studies and the development by Burg and colleagues for in vitro perfusion of surviving tubular segments have provided an enormous amount of information about glomerular function and the transport characteristics of all nephron segments in the normal and diseased kidney. PMID- 1458258 TI - [Importance of diets and their effect on fetal development: function and structure of the endocrine pancreas following protein deficiency during intrauterine life]. AB - When an isocaloric low protein diet (8% versus 20%) is administrated to rats during gestation, the fetus or the neonate has a lower body weight and the structure and function of the endocrine pancreas is altered: islet cell proliferation, islet size and islet vascularisation are reduced when compared with a control group. If these fetal islets are cultured during 7 days in vitro, they secrete less insulin than normal islets in response to an AA challenge. When these newborns are fed with a low protein diet until adult age and analyzed at 70 days, the same alterations of the endocrine pancreas persist: the in vitro insulin secretion of the isolated islets in response to AA is dramatically depressed although their response to glucose is normal. However in vivo glucose and insulin levels in response to oral glucose challenge are abnormal. In addition, permanent functional alterations seem to persist when induced in utero. A normal diet (20% protein) given from birth to adulthood does not restore a normal insulin response in vivo to an oral glucose challenge. PMID- 1458259 TI - [Report of the joint Commission of the Royal Academy of Medicine on the analysis of publications concerning the study of homeopathic preparations aimed at immunotherapeutic treatment of AIDS and cancer]. PMID- 1458260 TI - [Epistemological observations on the placebo]. PMID- 1458261 TI - [Refractory diarrhea in infants: experimental basis of current therapeutic perspectives]. AB - Intractable diarrhoea is a severe condition of early infancy producing prolonged food intolerance, massive watery diarrhoea and malnutrition. Although the etiology remains unknown in more than half of the cases, a basic physiopathological mechanism appears to be a variable inhibition of the maturation and differentiation of the crypt cell resulting in immature villus cells. Among the known nutritional and hormonal factors that control maturation of the enterocytes, polyamines (spermine, spermidine) emerge as the most trophic substances potentially useful for humans. Clinical studies are warranted to determine whether semi-elemental diets enriched in polyamines would provide some benefit for patients with intractable diarrhoea or with an adapted bowel after extensive enterectomy. PMID- 1458262 TI - [Cataract surgery: past, present and future]. PMID- 1458263 TI - New developments in bacterial arthritis. PMID- 1458264 TI - Genetics and osteoarthritis. PMID- 1458265 TI - Rheumatoid arthritis and depression: an overview. AB - Clearly, the determinants of depression in RA are complex and multifaceted. As with the disease itself, there is no simple cure for the depression that often accompanies it. Knowledge in this area is growing rapidly, however. Increasingly effective interventions are being developed to help those having difficulty adjusting to RA. As our understanding of the determinants of depression in RA increases, these therapies will continue to evolve. Ultimately, they may provide the long-term benefits desired by clinicians and patients alike. PMID- 1458266 TI - Early mortality in RA predicted by poor clinical status. PMID- 1458267 TI - Influencing mortality outcomes in RA. PMID- 1458268 TI - Exercise and osteoarthritis. PMID- 1458270 TI - The neglected male. PMID- 1458269 TI - Surgical enabling works. PMID- 1458271 TI - Dentistry in the community: the future. PMID- 1458272 TI - Clinical monitoring of neuromuscular function. AB - With the advent of shorter-acting non-depolarizing neuromuscular blocking drugs, the use of nerve stimulation as a means of monitoring the neuromuscular junction has become more widespread. This article describes the patterns of nerve stimulation and modes of monitoring muscular response in current clinical use. These patterns and modes are compared and their clinical relevance is discussed. PMID- 1458273 TI - Surgical management of Graves' ophthalmopathy. AB - While most patients with Graves' ophthalmopathy have minor or largely cosmetic problems, severe ocular morbidity can occur and lead to blindness or eye loss. In this article the role of surgery in the management of Graves' ophthalmopathy is reviewed. PMID- 1458274 TI - Illness and insight. AB - The term insight, when applied to illness, encompasses a patient's awareness and the personal significance of his/her disease, and the need for treatment. Insight is shaped by cultural, psychological and neurological factors. It affects attitudes to compliance and screening, levels of distress and may influence prognosis. PMID- 1458275 TI - Computers in respiratory medicine. AB - Information ranging from patient symptoms to bed state is essential for the efficient functioning of clinical services. Computers have a central role in organizing this information and this review illustrates the impact of their introduction on clinical hospital departments. PMID- 1458276 TI - Management of pregnancy in women with HIV infection. AB - HIV infection is a common medical problem in pregnancy in many parts of the world. Management involves supportive multiagency care, easy and effective communication, an awareness and understanding of other issues (which may be more important to the mother than her HIV infection), and specialists with both experience and an up-do-date knowledge base. PMID- 1458277 TI - How to prepare for your foreign fellow. AB - Visiting fellows on a 1-year sabbatical can take months to settle in and organize their personal lives. Some forward planning, a general information pack containing useful addresses and an introduction to relevant people can speed their integration. PMID- 1458278 TI - Repeated ventilatory arrest: consider tracheal tumours. PMID- 1458279 TI - How to titillate the parts that other videos cannot reach. PMID- 1458280 TI - Caution advised when changing to new therapies. PMID- 1458281 TI - French medical training: a comparison with the UK. PMID- 1458282 TI - Proceedings of the British Pharmacological Society Meeting. 9-11 September 1992. Abstracts. PMID- 1458283 TI - Provisional guidelines for measuring disease activity in clinical trials on rheumatoid arthritis. PMID- 1458284 TI - Performing arts medicine. PMID- 1458285 TI - Arthritis and rheumatism council fellowships. PMID- 1458286 TI - Localization of interleukin-1 alpha, type 1 interleukin-1 receptor and interleukin-1 receptor antagonist in the synovial membrane and cartilage/pannus junction in rheumatoid arthritis. AB - Using monoclonal antibodies and immunohistochemical techniques we have investigated the presence and distribution of interleukin-1 alpha (IL-1 alpha), type 1 IL-1 receptor (IL-1R1) and of interleukin-1 receptor antagonist (IL-1ra) in synovial tissue from 18 rheumatoid arthritis (RA) and eight osteoarthritis (OA) patients and in eight normal synovial tissue samples. IL-1 alpha and IL-1R1 were found in all of the samples examined. In RA, there were a large number of synovial cells expressing IL-1 alpha and IL-1R1, with 85 and 90% positive cells in the lining layer, 45 and 80% in the interaggregate area, and 90% of the vascular endothelial cells. In the lymphoid aggregates, 20% of the cells contained IL-1 alpha and 70% expressed IL-1R1. IL-1 alpha and IL-1R1 expressing cells showed a similar distribution in OA synovial membrane, but there was a smaller number of positive cells in the deeper area; and the staining intensity was lower. In contrast to IL-1 alpha and IL-1R1, IL-1ra was found only in 10/18 RA, 5/8 OA and 2/8 normal tissue samples. IL-1ra was detected in 35% of RA and 45% OA lining layer cells; 25% RA and 35% OA vascular endothelium; 10% RA and 15% OA interstitial cells and 30% cells in RA lymphoid aggregate. The staining intensity in both RA and OA tissues was comparably low. The presence of IL-1ra in RA and OA tissues was confirmed by Northern blot analysis for IL-1ra mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458287 TI - Clinical manifestations and anti-(U1)snRNP antibodies: a prospective study of 29 anti-RNP antibody positive patients. AB - Twenty-nine anti-RNP positive patients were followed prospectively with a mean observation time of 65 months (29-120 months). The clinical course was correlated to the presence of IgM and IgG anti-(U1)snRNP antibodies as revealed by immunoblotting from sequentially obtained sera. There was a striking dissociation between the fluctuating course, with the appearance of new manifestations followed by remissions, and the stability of the anti-snRNP antibody specificities where an appearance or a disappearance of anti-snRNP specificities was a rare phenomenon. The main epitope recognized by the IgG antibodies was the 70 kDa protein and of the IgM antibodies the B/B' proteins. No shift from the IgM to the IgG isotype was observed. The presence of IgG anti-70 kDa and IgM anti B/B' antibodies was highly associated with presence of arthralgias, Raynaud's phenomenon and arthritis. Further, an association was noted between the combined presence of IgG anti-70 kDa, anti-A and anti-C antibodies and IgM anti-B/B' and puffy hands, myositis, pulmonary fibrosis and sclerodactyly, i.e. all manifestations of mixed connective tissue disease (MCTD). On the contrary, serositis as often seen in SLE was correlated to the presence of IgG anti-B/B' antibodies. Thus the longitudinal analysis of the correlation between anti-snRNP antibody specificities and clinical manifestations support the concept of MCTD as a distinct entity. PMID- 1458288 TI - Postmenopausal screening for osteopenia. AB - Dual energy X-ray absorptiometry (DXA) measurements of bone mineral density (BMD) in the lumbar spine and femoral neck have been performed in 1000 consecutive women aged between 40 and 60 years referred for screening for osteopenia. A detailed history was taken from each woman that included relevant lifestyle parameters and known risk factors for osteoporosis. After exclusions, e.g. because of fractures, corticosteroid or prolonged HRT use, 627 women (mean age 53 years) were considered suitable for further analysis. The mean BMD in the lumbar spine (L1-L4) was 0.946 g/cm2 and in the femoral neck was 0.767 g/cm2. Significant correlations were found between BMD and years after the menopause and weight (range r = 0.20-0.24). However, these parameters are not reliable enough predictors of BMD to be of value in clinical practice. If osteopenia is to be the basis for initiating prophylactic measures against bone loss, then a threshold BMD must be chosen below which treatment will be advised. Since the correlation coefficient between spinal and femoral neck BMD measurements was only 0.64, assessment of any individual requires consideration of both sites. There is as yet no consensus as to the number of women who may require to be treated and we have provided BMD values that identify a range of population sizes (the lowest 20, 30, 40 and 50 percentiles). It should be noted that there was a 16% loss of BMD in the spine and 14% in the femoral neck during the first 5 years after the menopause.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458289 TI - A longitudinal study of pulmonary function in patients with rheumatoid arthritis treated with gold and D-penicillamine. AB - Sixty-two patients with classical or definite RA who were considered suitable for disease-modifying drug therapy were entered into a prospective longitudinal study to determine the long-term effects of commonly used drugs such as gold, D penicillamine and azathioprine on pulmonary function. Each patient had an assessment of pulmonary function, including spirometry, static lung volumes and diffusion tests, before starting drug therapy and at 6-monthly intervals during treatment. In those patients where drug therapy was discontinued, pulmonary functions were performed at withdrawal and 1 year later. Forty-six per cent of the patients in the 'gold group' and 21% in the 'penicillamine group' had developed a restrictive defect after 2 years. There was a significant reduction in vital capacity and transfer factor for carbon monoxide (P < 0.001) in both groups. A significant improvement in pulmonary function was found in the gold treated patients (P < 0.05) a year after treatment was discontinued. This study shows that a significant proportion of rheumatoid patients on second-line drugs such as gold and penicillamine develop chronic progressive pulmonary damage indistinguishable from fibrosing alveolitis or 'rheumatoid lung'. Its recognition is important as the condition is asymptomatic, slowly progressive and appears to be reversible on withdrawal of the drug therapy in the majority of the patients. PMID- 1458290 TI - Idiopathic inflammatory myopathy: clinicopathological observations in the Indian population. AB - The present study attempts to investigate the pathological basis of the two clinically different forms of idiopathic inflammatory myopathy (IIM) namely, polymyositis (PM) and dermatomyositis (DM). Clinicopathological analysis of 73 cases showed that muscle fibre necrosis and regeneration were more frequent in PM than in DM, the latter being significantly so (P < 0.05). On the other hand, vasculitis was more associated with DM while perifascicular atrophy of the muscle fibres was confined to it. Vasculitis was present in eight cases. Its incidence in patients with myositis with systemic connective tissue disease (4/9) was significantly more than in other PM and DM patients (P < 0.01). An equally significant higher frequency of perimysial inflammatory infiltrate was also seen in the former as compared to the latter. Interestingly, idiopathic DM affected men as often as women and juvenile IIM affected boys more frequently than girls. A female predilection was noted in the remaining groups of IIM. These observations indicate that there may be some basic immunopathogenetic differences between polymyositis and dermatomyositis as well as between idiopathic PM/DM and that associated with systemic connective tissue diseases. Though the number of patients studied is small, the absence of female predilection in idiopathic DM and juvenile IIM may be peculiar to the IIM in the tropics. PMID- 1458291 TI - What are the long term follow-up results of silastic metacarpophalangeal and proximal interphalangeal joint replacements? PMID- 1458292 TI - A study to compare the efficacy of two methods of skin preparation prior to joint injection. AB - This paper compares two methods of skin preparation in terms of their effectiveness in rendering the skin sterile, ease of use, and their cost. PMID- 1458293 TI - Rheumatology in Russia: an opportunity to help. PMID- 1458294 TI - A case of adult dermatomyositis treated with cyclosporin A. PMID- 1458295 TI - Spontaneous neutrophil activation in patients with primary Raynaud's phenomenon and systemic sclerosis. PMID- 1458296 TI - Infrared thermography: what is its place in rheumatology in the 1990s? PMID- 1458297 TI - Arthritis--a presenting feature of occult coeliac disease. PMID- 1458298 TI - A profile of the rheumatology nurse specialist in the United Kingdom. PMID- 1458299 TI - Antineutrophil cytoplasmic antibodies in rheumatoid arthritis. PMID- 1458300 TI - Methotrexate in older patients with rheumatoid arthritis. PMID- 1458301 TI - New treatments for cystic fibrosis. AB - The cornerstones of CF medical treatment remain optimised nutrition, antibiotics and chest physiotherapy. There are however a number of promising new approaches which may add considerably to these traditional treatments. The most fundamental prospective new treatment is gene therapy which is still a long way off but could, in theory, provide a virtual cure for the disease. Less visionary but potentially as important is drug therapy aimed at the basic defect in airway ion transport. Both of these approaches are best suited to patients with early or even pre-symptomatic disease. In contrast, a third group of new treatments may prove useful in patients with established lung damage; these include a variety of anti-inflammatory drugs and DNase. This chapter will discuss each of these new treatments as well as exploring the difficult issue of assessing new treatments in pre-symptomatic disease. PMID- 1458302 TI - Screening for cystic fibrosis. AB - Neonatal screening for cystic fibrosis (CF) reduces short-term morbidity but its long term effects remain to be demonstrated. The best available method is the assay of immunoreactive trypsin in dried blood spots, and specificity can be improved by adding direct or indirect genetic analysis. Pregnancies known to be at risk of CF can also be screened by molecular methods, and affected pregnancies terminated. The application of genetic testing to whole communities, to detect unknown heterozygotes, raises many questions which require consideration by society and the health professions. The development of effective treatment of the basic abnormality of cell function in CF would enhance the need for neonatal screening, and possibly reduce the requirement for abortion. PMID- 1458303 TI - Cystic fibrosis: nutrition. AB - There has been renewed interest in examining the multiple causes of undernutrition and growth failure in cystic fibrosis. It is now recognized that undernutrition is caused by unfavourable energy balance rather than an inherent component of the disease. Furthermore, there appears to be a direct association between the degree of undernutrition and the severity of pulmonary disease, which in turn affects overall prognosis. Energy imbalance may be caused by three main factors: increased energy loss because of nutrient maldigestion; reduced energy intake due to an improper diet and/or anorexia from respiratory disease, abdominal symptoms or clinical depression and increased energy expenditure with advanced lung disease. Most patients are capable of compensating for these factors; provided energy intake is sufficient, normal growth velocity and nutritional status is maintained. However, in a minority of older patients, when advanced lung disease supervenes, energy expenditure rises resulting in an energy deficit. Undernutrition, with loss of energy stores and lean tissue may in turn contribute to progressive deterioration of lung function. When this occurs, long term invasive methods of nutritional support can restore energy balance. PMID- 1458304 TI - Cystic fibrosis: gastrointestinal complications. AB - An individual who has cystic fibrosis (CF) may suffer from gastrointestinal problems related to inadequately controlled intestinal absorption secondary to the pancreatic insufficiency. These include neonatal meconium ileus, distal intestinal obstruction syndrome (DIOS), constipation and acquired megacolon, rectal prolapse and rarely pancreatitis. If the intestinal malabsorption is well controlled with an effective pancreatic enzyme preparation, DIOS, constipation and rectal prolapse are infrequent. Persisting gastrointestinal symptoms should be investigated thoroughly to exclude other disorders not directly related to the cystic fibrosis; these include cows' milk intolerance, coeliac disease, giardiasis, Crohn's disease and intra-abdominal malignancy. Both appendicitis and intussusception may cause difficult diagnostic problems particularly in patients who may also have distal ileal obstruction syndrome. PMID- 1458305 TI - Cystic fibrosis: bile secretion. AB - Bile is an isotonic aqueous solution of bile acids, cholesterol, phospholipids, bile pigments and inorganic electrolytes. It is secreted by the hepatocytes into the bile canaliculi and modified in the bile ductules or ducts. The three main processes identified in the generation of bile flow are: 1. Active transport of bile acids from blood into bile canaliculi. This is responsible of the bile acid dependent canalicular bile flow. Coupling between water flow and bile acid secretion is probably effected mainly through an osmotic mechanism. There is evidence that water flows (at least in part) through the interhepatocytic junctions. The bile acid-dependent flow accounts for 30 to 60% of spontaneous basal bile flow. 2. A canalicular, bile acid-independent secretion, probably due to transport into bile of organic solutes (glutathione) and inorganic electrolytes. This fraction of bile flow is stimulated by phenobarbital. It represents 30 to 60% of basal bile flow. Normal canalicular bile flow also depends on the integrity of intracellular cytoskeletal organelles, mostly microfilaments. 3. Reabsorption and secretion of fluid and inorganic electrolytes by the ductules and ducts. Secretion chiefly occurs in response to secretin and represents 30% of basal bile flow. Although several ion transport systems have been identified on the biliary epithelial cells (in particular a Na+/H+ exchange, a Na+:HCO3- symport and a CI-/HCO3- exchange), the cellular mechanism of secretion is not known. Abnormalities of bile duct function may account for the liver disease of cystic fibrosis, but these abnormalities have not been characterized. PMID- 1458306 TI - Liver and biliary problems in cystic fibrosis. AB - There have been striking advances in the management of complications of cirrhosis in the 50 years since biliary cirrhosis was recognised as a feature occurring in a minority of patients with cystic fibrosis. Many questions remain unanswered with regard to its pathogenesis, its effect on other systems, morbidity and mortality and to its optimum management. Factors which may initiate liver disease and/or cause progressive biliary fibrosis leading to biliary cirrhosis in some cystic fibrosis patients are being defined but much is still poorly understood and further research is required. Clinical and pathological studies confirm that cirrhosis is frequently asymptomatic and only slowly progressive, with the prevalence rising with age. In a recent large epidemiological study, however, it was found that the age related prevalence fell in patients over the age of 20 years although deaths from liver disease were rare. Does the presence of liver disease cause premature respiratory death in teenagers? Current treatments control variceal bleeding, the important sequel for most patients with biliary cirrhosis, with less morbidity and mortality than in the past but require reappraisal as newer techniques become available. Endoscopic radiologically controlled methods are emerging as an important adjunct to the surgical control of biliary complications which cause symptoms in up to 4%. Ursodeoxycholic acid improves liver function tests but its effect on hepatic fibrosis and portal hypertension will only be demonstrated by large scale prospective controlled trials. Should liver transplantation have a larger role in management? In this chapter we have attempted to summarise the current state of knowledge and to assess the efficacy of present management. PMID- 1458307 TI - Immunology of cystic fibrosis. AB - The combination of all the immunological abnormalities described in CF appear to have a final common pathway through effects on neutrophils. Potent neutrophil chemotactic factors are produced as a result of antibody-antigen interactions leading to complement activation and the generation of C5a and the many cytokines released as a result of cellular immune responses leading to neutrophil influx and activation. In addition, the product of bacterial metabolism fMLP also produces neutrophil chemotaxis. The activated neutrophils release a range of proteases and oxygen radicals which directly damage tissues. It can, therefore, be hypothesised that the excessive immune response is directly contributing to the tissue damage. Indeed, it is even possible that this is the principal cause of the lung function defect without invoking any direct influence of the infecting organisms. This, of course, has major implications for approaches to therapy. Currently the main focus is on suppression of the organisms. However, modulation of the immune response is an attractive alternative approach. PMID- 1458308 TI - Cystic fibrosis: respiratory problems and their treatment. PMID- 1458309 TI - Lung transplantation for cystic fibrosis. AB - Significant progress has been made since the first successful human heart-lung transplantation (HLT) for pulmonary vascular disease performed in 1981. The refinement of surgical techniques, use of cyclosporin as the main immunosuppressant, technique of distant organ procurement to expand the donor organ pool, and improved diagnosis and management of pulmonary infection and rejection have all contributed to this accomplishment. This has inevitably coincided with the extension of this procedure to other groups of patients with end stage heart and lung disease. Initially, HLT was offered to patients with cardiac disease associated with pulmonary hypertension. Because of the success, consideration was given to transplantation for parenchymal pulmonary diseases, initially pulmonary fibrosis and emphysema, and then suppurative lung disease such as in cystic fibrosis (CF). However, the application of HLT to patients with CF lagged behind because of concern related to the risk of sepsis, the systemic nature of the disease, malnourishment, and fear of recurrence of the epithelial CF defect in the transplanted lungs. PMID- 1458310 TI - Reduction of glutamate release and protection against ischemic brain damage by BW 1003C87. AB - BW 1003C87, 5-(2,3,5-trichlorophenyl)-2,4-diaminopyrimidine ethane sulphonic acid, has been tested for its in vitro and in vivo effects on glutamate release in rat brain tissue, and for its cerebro-protective action in two rodent models of cerebral ischemia. In rat brain slices the release of glutamate evoked by veratrine is inhibited by BW 1003C87 (IC50 = 1.6 microM). In anaesthetised rats with microdialysis probes implanted in the dorsal hippocampus the increase in extracellular glutamate evoked by veratrine is markedly reduced by co-infusion of BW 1003C87, 100 microM. In anaesthetised rats with microdialysis probes implanted in the cortex and the caudate nucleus ipsilateral to a middle cerebral artery (MCA) occlusion the increase in dialysate glutamate concentration seen in the first 2 h following MCA occlusion is markedly attenuated by the prior administration of BW 1003C87, 20 mg/kg i.v. In rats subjected to 10 min of bilateral common carotid artery occlusion the loss of CA1 pyramidal neurons (assessed 7 days later) is reduced by administration of BW 1003C87 (20 mg/kg i.v., at the time of ischemia and 4 h later). The volume of cortex showing infarction 72 h after unilateral MCA occlusion is reduced by treatment with BW 1003C87 (20 mg/kg, i.v., beginning 5 min after occlusion). Inhibition of glutamate release may provide a therapeutic approach in cerebral ischemia as well as in epilepsy. PMID- 1458311 TI - Neurons in the hypothalamic paraventricular nucleus mediate the serotonergic stimulation of renin secretion. AB - The aim of the present study was to resolve which hypothalamic nucleus is necessary for the serotonergic control of renin secretion. RU 24969 is considered a serotonin (5-HT1A/5-HT1B) agonist, while p-chloroamphetamine is a 5-HT releaser. Both drugs reliably elevate plasma levels of renin when injected peripherally. Previous studies suggest that serotonergic neurons, projecting to the hypothalamus, mediate the effect of p-chloroamphetamine on renin secretion. Discrete cell-selective lesions were made with ibotenic acid in three hypothalamic sites: the paraventricular, the dorsomedial or the ventromedial nuclei. Two weeks after surgery rats were injected with RU 24969 (5 mg/kg, i.p.) or p-chloroamphetamine (8 mg/kg, i.p.). The renin response to both RU 24969 and p chloroamphetamine was significantly reduced in rats with histologically verified paraventricular lesions compared to vehicle treated controls. In contrast, the renin response to p-chloroamphetamine remained unchanged in rats with either dorsomedial or ventromedial hypothalamic lesions. Thus, these results are consistent with the hypothesis that 5-HT receptors located on cell bodies in the paraventricular nucleus mediate the renin response to a serotonin agonist and releaser. Furthermore, they confirm previous studies that suggest that 5-HT neurons regulate renin secretion through central receptors. PMID- 1458312 TI - Potentiation of cyanide neurotoxicity by blockade of ATP-sensitive potassium channels. AB - Exposure of primary hippocampal cultures to NaCN (2 mM) or glyburide (5 microM) alone for 3 h did not produce a rise in extracellular lactic dehydrogenase (LDH) activity. Coincubation with NaCN and glyburide produced a significant efflux of LDH from the neurons. Diazoxide or D-2-amino-5-phosphovalerate (APV) partially reversed the release of LDH by the combination of NaCN and glyburide. These observations indicate ATP-sensitive potassium channels (KATP) are activated by nonlethal concentrations of cyanide and their blockade with glyburide unmasks cyanide's toxicity. The cytotoxicity of cyanide appears to result from a combination of processes resulting in altered ion handling and excitotoxicity. PMID- 1458313 TI - Accumulation of amyloid precursor protein in damaged neuronal processes and microglia following intracerebral administration of aluminum salts. AB - Alzheimer's disease is characterized by neurofibrillary tangles and amyloid deposits, with the latter probably occurring because of abnormal accumulation and/or processing of amyloid precursor protein (APP). Aluminum salts are known to be neurotoxic and to be capable of inducing neurofibrillary tangles. We explored the effects of intraventricular or intrastriatal injections of AlCl3 on the immunodistribution of APP in rat brain. There was a striking and long-lasting accumulation of APP in affected neurites, as well as in activated microglia/macrophages. Abnormal neurites also showed argentophilic changes, neurofilament accumulation, and Alz50 immunoreactivity. However, no extracellular amyloid fibrils were seen. The results, taken together with previous studies on colchicine, are consistent with the hypothesis that interruption of axoplasmic flow can lead to both APP accumulation and cytoskeletal changes. PMID- 1458314 TI - Ketamine blocks the induction of LTP at the lateral entorhinal cortex-dentate gyrus synapses. AB - In many regions NMDA receptor activation is required for the synaptic induction of long-term potentiation (LTP). This role for NMDA receptors is controversial at the synapses formed between the cells of the lateral entorhinal cortex (LEC) and the dentate gyrus (DG). Using anesthetized rats, the present study shows that ketamine reversibly blocks the induction of LTP at the LEC-DG synapses, thus favoring a role for NMDA receptors in the induction of LTP there. Ketamine also reversibly blocks the induction of the small translaminar depression of the medial EC response or of the LEC response by conditioning the other system while the test system is inactive. PMID- 1458315 TI - Amyloid precursor protein accumulates in regions of neurodegeneration following focal cerebral ischemia in the rat. AB - The distribution of beta-amyloid precursor protein (APP) was examined immunocytochemically in rats subjected to focal cerebral ischemia by permanent occlusion of the middle cerebral artery. At 4 and 7 days post-occlusion, APP immunoreactivity was preferentially localized within axonal swellings, dystrophic neurites and neuronal perikarya all along the periphery of the infarct. Immunolabeling was observed with antibodies generated against N-terminal, midregion, and C-terminal domains of APP. No immunoreactivity was observed with antisera directed against beta-amyloid protein (beta A4) itself. This pathological accumulation of APP is consistent with alterations of APP recently described in other models of neurodegeneration and implies a role for this protein in the response to CNS injury. PMID- 1458316 TI - Hypotension preferentially induces c-fos immunoreactivity in supraoptic vasopressin neurons. AB - Immunoreactivity to Fos protein (Fos-IR) was detected in rat hypothalamic neurons within 1 h of onset of hemorrhage by withdrawing 4-5 ml of blood, which lowered the arterial blood pressure to 50-70 mm Hg. About 70% of vasopressin (AVP) containing neurons in the supraoptic nucleus (SON) and 20% in the paraventricular nucleus (PVN) expressed Fos-IR. In contrast, 5% of oxytocin (OXY)-containing neurons in the SON and < 1% in PVN were Fos-IR. Intravenous infusion of the vasodilating agent, nitroprusside, which lowered the blood pressure to levels comparable to that attained by hemorrhage, induced Fos-IR in greater than 65% of AVP-containing neurons in the SON, while relatively few AVP neurons in the PVN were Fos positive. These results suggest that hemorrhage or hypotension preferentially induces c-fos expression in supraoptic AVP-containing neurons. PMID- 1458317 TI - Age-related changes of motor evoked potentials in healthy humans: non-invasive evaluation of central and peripheral motor tracts excitability and conductivity. AB - A comparative analysis of the corticospinal tract nervous propagation and excitability threshold was carried out in young (25 subjects, age range 16-35 years) and in elderly (40 subjects, 51-86 years) populations of healthy volunteers. Motor evoked potentials (MEPs) were recorded from the hand and foot muscles following transcranial magnetic stimulation (TCS) during complete relaxation and active contraction of the target muscles. Threshold intensities corresponded to the stimulator's output eliciting liminal MEPs in about 50% of stimuli during relaxation. It was found that threshold values of magnetic TCS were significantly higher in the elderly (44 +/- 6.4% vs 39 +/- 3.5% for the hand; 66 +/- 10.1% vs 56 +/- 6.7% for the foot; P < 0.001) than in the young subjects. Moreover, this index progressively increased with age (P < 0.001), whilst the propagation time along the central motor tracts did not parallel such an age-related trend. PMID- 1458318 TI - Stimulation of cholecystokinin (CCK) release from superfused rat hypothalamo neurohypophyseal complexes by interleukin-1 (IL-1). AB - This in vitro study examined the effects of interleukin-1 (IL-1) and interferon gamma (Ifn-gamma) on the release of cholecysto-kinin (CCK) from superfused hypothalamo-neurohypophyseal complexes (HNC) of rats. An increase of CCK from HNC was elicited in a dose-dependent manner by recombinant human IL-1 alpha and -1 beta in concentrations of 0.1-10 nM. In contrast, the release of CCK from HNC was not affected by recombinant human Ifn-gamma at any dose tested (0.1, 1 and 10 nM). The increased release of CCK elicited by IL-1 was calcium-dependent, as was that induced by potassium (60 mM), but it was biphasic and had a different time course and a lower magnitude than those induced by potassium and veratridine. These results suggest that IL-1 activates pituitary-adrenal axis by stimulating CCK neurons in the hypothalamus and/or neurohypophysis to release CCK, since CCK has been implicated in the regulation of adrenocorticotropin release. PMID- 1458319 TI - Extracellular calcium is a mediator of astroglial injury during combined glucose oxygen deprivation. AB - We tested the hypothesis that extracellular calcium is a mediator of astroglial injury during combined glucose-oxygen deprivation. Both differentiated and undifferentiated astroglial cultures were exposed to combined glucose-oxygen deprivation in the presence and absence of extracellular calcium. Lactate dehydrogenase efflux was used as an index of cellular injury. Both types of cultures exhibited significantly less cellular injury when exposed to combined glucose-oxygen deprivation in the absence of extracellular calcium (e.g. lactate dehydrogenase efflux in undifferentiated cultures after 12 h of exposure: presence of calcium, 65.2 +/- 2.5% vs. absence of calcium, 21.4 +/- 1.3%). To further elucidate the mechanism by which extracellular calcium produces injury, we studied the effect of nimodipine, an L-type calcium channel blocker, on astroglial injury resulting from combined glucose-oxygen deprivation. Nimodipine decreased cellular injury in both types of cultures (e.g. lactate dehydrogenase efflux in undifferentiated cultures after 12 h of exposure: untreated, 65.4 +/- 2.2% vs. 10 nM nimodipine, 44.6 +/- 4.2%). Extracellular calcium appears to be a mediator of astroglial injury during combined glucose-oxygen deprivation. These results suggest that influx of extracellular calcium via L-type voltage-gated calcium channels may contribute to astroglial injury during cerebral ischemia. PMID- 1458320 TI - Measurement of gamma-enolase release, a new method for selective quantification of neurotoxicity independently from glial lysis. AB - We have developed a sensitive enzymatic-immunoassay to quantify the level of gamma-enolase (a specific neuronal enzyme) which is released from cultured cells after exposure to various toxins. We show that this method can estimate selectively neuronal cell death without significantly interfering with glial cell death. Indeed, no gamma-enolase is released when glial cells are killed with free radical producing agents. Experiments comparing the levels of neuronal cell death induced by NMDA or free-radical producing drugs, performed either by measuring gamma-enolase release or using the classical fluorescein diacetate method, yielded similar results. In addition to selectively follow neuronal death in a mixed population of neurons and glial cells, this method provides a way of determining the cell death kinetics from a single culture dish, since enolase can be measured on small samples taken from the culture medium. Finally, we propose these two methods as being complementary and useful neuronal and other cellular death indexes and also to understand the complex problem of glial influence on neuronal survival or death. PMID- 1458321 TI - Enduring increase in membrane-associated protein kinase C activity in the hippocampal-kindled rat. AB - In a previous study we demonstrated that the membrane-associated protein kinase C (PKC) activity in the amygdala/pyriform cortex (AM/PC) and both the right and left hippocampus (HIPP) of rats kindled from the left HIPP increased significantly 4 weeks after the occurrence of the last seizure compared with control rats. In this study, we carried out further investigations into the enduring effect of HIPP-kindling on membrane-associated PKC activity, the protein concentrations and brain wet tissue weights of the AM/PC and right (contralateral) and left (ipsilateral) HIPP 15-16 weeks after the last generalized kindled seizure had occurred. In addition, we determined the membrane associated PKC activity one week after the occurrence of the last partial (stage 1-3) seizure. Fifteen to sixteen weeks after the final kindled full seizure, the membrane-associated PKC activity which was expressed as mol/min per mg protein increased significantly in the AM/PC (by 62%, P < 0.02) and left HIPP (by 33%, P < 0.03) compared with control rats, whereas the cytosolic PKC activities did not differ in any brain region examined. The wet tissue weight increased significantly (by 10%, P < 0.04) in the left HIPP only. Furthermore, when it was expressed as pmol/min per mg wet tissue weight, the membrane-associated PKC activity increased significantly in the AM/PC (by 47%, P < 0.02), right HIPP (by 27%, P < 0.05) and left HIPP (by 35%, P < 0.03) compared with the controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458322 TI - Normal equine ocular anatomy and eye examination. AB - When compared with small domestic animals, the horse has unique ocular characteristics (complete bony orbit, well-developed eyelid muscles, a nasal and temporal gray limbal line, granulae iridica, paurangiotic fundus). Knowledge of normal equine ocular anatomy is essential for ocular lesion interpretation. It is important to obtain a full history and general examination before sedation, nerve blocks, or other diagnostic ophthalmic tests are performed. All ocular examinations should include a systematic evaluation of both the anterior and posterior segments. Selection of other diagnostic tests depends on information obtained from the history, general inspection, and ophthalmic examination. The appropriate order of performing various special diagnostic tests must be considered before beginning the examination. If a diagnosis is elusive, referral to an ophthalmologist for further diagnostics should be considered. PMID- 1458323 TI - Equine vision and optics. AB - Vision is a marvelous sense, critical to the well-being and functional use of horses. Anatomic, optical, and visual acuity generalities are presented. The constituents of unsoundness due to equine ocular disease are discussed, and recommendations are made. PMID- 1458324 TI - Congenital ocular anomalies. AB - This discussion provides an idea of the diversity and relative prevalence of certain congenital ocular conditions of horses. Many are not difficult to diagnose, yet curative treatment may be impossible. When dealing with owners of horses affected with unusual anomalies, responsible client service requires veterinarians to provide accurate information and to know where answers to unusual questions can be found. Again, most veterinarians never encounter all of the diverse congenital defects. As a result, the horse owner frequently receives misinformation. Hopefully, this brief coverage of congenital ocular anomalies will provide useful information and assist in appropriate communication to concerned parties. PMID- 1458325 TI - Principles of therapeutics. AB - Topical administration of drugs is the treatment of choice for diseases of the anterior segment. Drug levels attained by this means are usually of short duration, however, necessitating frequent therapy or continuous perfusion if prolonged drug levels are required. A drug-delivery device (collagen shield or contact lens) or subconjunctival injections can be used to augment topical therapy if frequent treatment is not possible. Subconjunctival injections are recommended for drugs that have low solubility and, hence, low corneal penetration. Retrobulbar injections are seldom indicated, except for regional anesthesia. Systemic administration is useful for anti-inflammatory therapy but it may be difficult to establish therapeutic levels of antibiotic agents in the eye because of the blood-ocular barrier. In severe cases, intraocular injection may be required. PMID- 1458326 TI - Eyelid and nasolacrimal disease. AB - An understanding of normal structure and function of the equine eyelid is essential to make an accurate diagnosis and appropriately treat equine eyelid diseases. Entropion, eyelid trauma, neoplasia, and nasolacrimal disorders are reviewed. Methods of diagnosis and treatment are presented. PMID- 1458327 TI - Ocular trauma. AB - Horses with ocular trauma frequently present as emergency cases. This article provides a succinct review of various adnexal and globe injury issues. Accurate case assessment, management, prognosis, and follow-up considerations are presented. PMID- 1458328 TI - Equine ulcerative keratitis. AB - Ulcerative keratitis is one of the most common vision-threatening diseases of the horse. Successful therapy, however, can be achieved in the majority of cases provided the diagnosis is made early and the treatment is specific for the disease. This article reviews the pathophysiology, clinical signs, and contemporary medical and surgical approaches to bacterial and fungal ulcerative keratitis in the horse. PMID- 1458329 TI - Equine uveitis. AB - Uveitis (inflammation of the iris, ciliary body, or choroid) is a potentially blinding condition with a significant economic impact on the horse industry. Variable symptoms are described, as well as a considerable range of structural and functional sequelae. Known causes of initial episodes include bacterial, viral, traumatic, and parasitic insults, with recurrence by immunologic mechanisms. Treatment strategies and management recommendations that may reduce the incidence or severity of episodes are discussed. PMID- 1458330 TI - Diagnosis and treatment of lens diseases. AB - The lens represents a unique tissue in light of its embryologic development, retention of old cells and nuclear make-up, transparent nature, immune privileged status, and metabolic restrictions. Disorders of malformation and malposition occur, but cataract development is the most common and significant problem for owners and animals. Technologic and pharmacologic advances have allowed surgical removal of equine cataracts to become an acceptable alternative, capable of returning a visually impaired horse to a functional status. Uveal inflammation represents the greatest threat to successful surgical cataract removal. Veterinarians should consult with those versed in ophthalmology for assistance in diagnosis, prognosis, peroperative treatment, surgical intervention, and follow up on lens disorders. PMID- 1458331 TI - Retinal and optic nerve diseases. AB - Basic knowledge of the normal appearance and variations of the equine fundus coupled with frequent practice in ophthalmology will allow equine practitioners to be confident when assessing the equine fundus during ophthalmic examinations. Once the normal variations are mastered, appreciation of retinal, choroidal, optic nerve, and vitreal abnormalities is possible. Congenital and acquired lesions of the equine retina, optic nerve, and vitreous are discussed and illustrated. PMID- 1458332 TI - Ocular neoplasia. AB - Except for two neoplasms, notably SCC and sarcoid, ocular and periocular tumors are uncommon in horses. The practitioner must accurately determine the type of tumor by histopathology so appropriate treatment and a legitimate prognosis can be offered. The first attempt at treatment has the greatest chance to result in a cure; an aggressive treatment regimen therefore should be selected from the start. PMID- 1458333 TI - Ocular manifestations of systemic diseases. AB - The diseases included in this article constitute a wide range of maladies that affect the horse. Certainly, the diseases that are known today to produce ocular lesions are just a few of what will be discovered if attending veterinarians always examine the eyes of patients with systemic diseases. PMID- 1458334 TI - Ocular cosmetic and prosthetic devices. AB - Specific details on surgical procedures, although not covered here, are available in other references. Factors enhancing the overall cosmetic appearance obtained with procedures are emphasized, providing information that should allow veterinarians to offer clients a good cosmetic appearance and effective treatment for disfiguring ocular problems in their horses. Questions regarding procedures should be addressed to your referral ophthalmologist or, in the case of a corneoscleral prosthesis, the ocularist assisting. PMID- 1458335 TI - Bone strength: the bottom line. PMID- 1458336 TI - Minimal levels of serum estradiol prevent postmenopausal bone loss. AB - Biochemical parameters reflecting bone resorption [urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OH/Cr)] were related to serum estrogens [estrone (E1) and estradiol (E2)] in 262 healthy women including 158 patients receiving estrogen replacement therapy (ERT) for at least 6 months, 49 eugonadal women, and 55 untreated postmenopausal women. A significant (P < 0.001) correlation exists between serum E2 and Ca/Cr: Ca/Cr (mg/dl) = -0.00044 E2 (pg/ml) + 0.129 (n = 262; r = -0.37), serum E2 and OH/Cr: (OH/Cr (mg/g) = -0.049 E2 (pg/ml) + 18.76 (n = 262; r = -0.36), serum E1 and Ca/Cr: Ca/Cr (mg/dl) = 0.0003 E1 (pg/ml) + 0.127 (n = 261; r = -0.28) but not between serum E1 and OH/Cr. Women with circulating levels of E2 between 60 and 90 pg/ml have a significant (P < 0.01) reduction of Ca/Cr and OH/Cr when compared with those with lower levels of E2. Higher values of E2 do not provide additional benefit. We conclude that in postmenopausal women receiving an estrogen replacement therapy (ERT), a significant reduction of bone resorption is achieved when circulating levels of estradiol reach a value (60 pg/ml) corresponding to the one measured, in eugonadal women, during the last days of the early follicular phase of the menstrual cycle. We suggest that oral or percutaneous ERT should induce a minimal value of 60 pg/ml to prevent postmenopausal bone loss. PMID- 1458337 TI - Measurement of estrogen and progesterone receptors in abnormal human parathyroid tissue. AB - Estrogen and/or progestin administration to postmenopausal women with primary hyperparathyroidism lowers serum calcium. We measured cytosolic estrogen receptors (ER) and progesterone receptors (PR) by classical hormone-receptor binding techniques in parathyroid tissue removed from 10 men and 20 women, and ER by immunocytochemistry in tissue from an additional one man and seven women in order to ascertain whether these agents might exert a direct effect upon tissue responsible for hyperparathyroidism. ER were negative (< 3.1 fmol bound estradiol/10 mg tissue) in all 8 adenomas and 4 of 5 secondary hyperplasias removed from men, and from women in 19 of 22 adenomas, 2 of 3 secondary hyperplasias, and 3 of 4 primary hyperplasias. PR were negative (< 10.1 fmol bound progesterone/10 mg tissue) in 7 of 8 adenomas and all 5 secondary hyperplasias removed from men, and from women in 20 of 22 adenomas, all 3 secondary hyperplasias, and all 4 primary hyperplasias. For immunocytochemical studies, quick-frozen specimens were analyzed with a monoclonal antibody (Abbott Laboratory) directed at nuclear ER. All eight samples--five adenoma and three primary hyperplasia--were negative. We conclude that abnormal human parathyroid tissues have nondetectable levels of ER and PR. It is unlikely that estrogen and progesterone exert a direct, ER, or PR-mediated effect upon parathyroid tissue. PMID- 1458338 TI - Bone marrow plays a role in bone metabolism: histomorphometry of iliac bone in postmenopausal women. AB - We conducted a histomorphometrical study on the role of the bone marrow in cancellous bone metabolism using iliac bone specimens from 79 postmenopausal women. A gradual decrease in hematopoietic tissue of the bone marrow was proportionate to the decrease in cancellous bone and the ratio of osteoid perimeter/bone perimeter regardless of age. On the other hand, the ratio of eroded perimeter/bone perimeter remained almost steady until hematopoietic tissue decreased significantly. These findings suggest that a change in the bone marrow, that is, a decrease in hematopoietic tissue, causes an imbalance in bone formation and resorption and leads to bone loss. PMID- 1458339 TI - Comparative assessment of bone mineral density of the forearm using single photon and dual X-ray absorptiometry. AB - Forearm bone mineral density (BMD) was measured at proximal and distal sites by 125I single photon absorptiometry (SPA) and by dual energy X-ray absorptiometry (DXA) in 67 consecutive subjects, aged 18-75 years. Correlations and regression equations between these two techniques were determined. All forearm measurements were significantly correlated with each other (r = 0.599-0.926; P < or = 0.0001). Although SPA and DXA correct for fat in different ways, we found similar correlation and regression equations in women with body mass index measurements above and below the mean. In addition, forearm measurements by both techniques were moderately correlated with vertebral spine and hip BMD. We conclude that overall, SPA forearm measurements in a population can be calibrated to DXA measurements if necessary, and that DXA forearm measurements are as predictive of the remainder of the skeleton as SPA measurements. PMID- 1458340 TI - Isolation and characterization of human embryonic osteoblasts. AB - Human osteoblasts were obtained by migration and proliferation of cells from embryonic membranous bone on glass fragments. Light and electron microscopy analyses revealed a typical osteoblast-like appearance with high protein synthesis activity. The cells showed high alkaline phosphatase activity that was associated with plasma membranes and matrix vesicles and was 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] responsive. In contrast to the adult osteoblasts, embryonic cells could not produce detectable levels of osteocalcin, not even in the presence of 1,25(OH)2D3. Osteoblasts grown in multilayers produced a thick extracellular matrix, mainly composed of type I collagen, that mineralized in the presence of 10 mM beta-glycerophosphate. Because of their intrinsic osteogenic capacity, embryonic osteoblasts represent a valuable model for studying the mineralization process in vitro. In addition, the embryonic origin of these cells renders them a precious experimental system for the elucidation of mechanisms at the basis of differentiation of osteoblastic lineage. PMID- 1458341 TI - Nacre initiates biomineralization by human osteoblasts maintained in vitro. AB - When nacreous shell produced by the marine oyster Pinctada maxima, used as a biomaterial in oral surgery, is implanted in human bone, new bone formation occurs, resulting in a tight welding of the bone to the nacre [16]. These findings are consistent with the possibility that nacre adjacent to bone can locally stimulate osteogenic activity. To test this hypothesis, we have evaluated the effect of the simultaneous presence of bone and nacre on human osteoblasts in vitro. Nacre chips (1 mm3) were placed at approximately 1 mm distance from a similarly sized bone chip on a layer of first passage human osteoblasts. None of the chemical inducers generally required to obtain bone mineralization in vitro (in particular, beta-glycerophosphate) was added to the cultures. Mineralized sections of the cultures were evaluated by light and electron microscopy, contact microradiography, and Laser Raman Spectroscopy. The results demonstrated that nacre has strong osteogenic effects on human osteoblasts when placed in proximity to bone in vitro. New bone formation occurred by both appositional growth on the existing bone and by the formation of mineralized nodules within the matrix adjacent to the bone explant. Electron microscopic evaluation of these sites demonstrated findings typical of those described in the course of bone formation in vivo, and no evidence of toxicity was observed. In addition, under the conditions of culture used, nacre can also promote the formation by osteoblasts of a structure with characteristics similar to nacre (e.g., lamellar organic matrix mineralized with aragonite, as demonstrated by Laser Raman Spectroscopy).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458342 TI - Characteristics of steroid hormone receptors in cultured MC3T3-E1 osteoblastic cells and effect of steroid hormones on cell proliferation. AB - We examined the binding characteristics of three kinds of steroid hormones- estrogen, androgen, and glucocorticoid--in cultured MC3T3-E1 mouse osteoblastic cells by whole-cell binding assay. The binding studies revealed the presence of a single class of high-affinity binding sites for [3H]17 beta-estradiol, [3H]mibolerone (a synthetic androgen), and [3H]triamcinolone acetonide (a synthetic glucocorticoid). The numbers of binding sites for these steroid hormones were found to be 4534 +/- 819, 14312 +/- 1884, and 24898 +/- 655 sites/cell; and the Kd values were 8.57 +/- 0.62 x 10(-10) M, 1.12 +/- 0.19 x 10( 9) M, and 6.08 +/- 1.24 x 10(-10) M, respectively. We also examined the effects of steroid hormones on the proliferation of MC3T3-E1 cells. 17 beta-estradiol significantly stimulated the proliferation of the cells (130-150% of control). Dihydrotestosterone also significantly stimulated the proliferation of the cells (115% of control); the effect was, however, much less potent than that of 17 beta estradiol, although the number of binding sites was approximately three times more than that of 17 beta estradiol. Triamcinolone acetonide and dexamethasone had no effect on cell proliferation. These results suggest that estrogen and androgen act directly on osteoblastic cells through a receptor-mediated mechanism, and that androgen is much less potent than estrogen in stimulating the proliferation of MC3T3-E1 osteoblastic cells. PMID- 1458343 TI - Interactions of tumor necrosis factor with local and systemic factors in fetal rat limb bones. AB - In many tissues the actions of tumor necrosis factor-alpha (TNF) are indirectly mediated through the production of autacoids or other cytokines. To determine the role that these factors might have in the action of TNF on bone resorption, we examined the effects of several selective inhibitors on TNF-stimulated resorption. The cyclooxygenase inhibitor indomethacin did not prevent TNF stimulated resorption in fetal rat limb bones. Stimulation of resorption by TNF was also unaffected by the platelet activating factor antagonist WEB 2086. A 17.5 kD interleukin receptor antagonist protein, at concentrations that completely blocked the bone-resorbing actions of maximally effective concentrations of interleukin (IL)-1 beta, failed to affect the stimulatory actions of TNF. TNF stimulated resorption was inhibited by both interferon-gamma and dexamethasone. Dexamethasone inhibited TNF-stimulated resorption more effectively than it inhibited parathyroid hormone (PTH)-stimulated resorption. When bones were treated simultaneously with low concentrations of TNF and PTH, potentiation of the bone-resorbing effects was elicited. These results suggest that TNF stimulates resorption through a pathway different from that by which PTH produces its effects. Transforming growth factor-beta (TGF-beta) enhanced responses to TNF; TGF-beta failed to inhibit the effects of TNF, even in long-term culture or when bones were pretreated with TGF-beta. Synergistic interactions between TNF and several other bone-resorbing factors have now been demonstrated. In contrast to the actions of TNF on certain other functions, the bone-resorbing effects of TNF, as determined in the fetal rat limb bone system, do not seem to be mediated by PAF, IL-1, or prostaglandins. PMID- 1458344 TI - Primary and secondary culture of rat ameloblasts in serum-free medium. AB - Enamel is the hardest tissue in vertebrates. Ameloblasts are derived from epithelial cells and are responsible for enamel formation. They secrete enamel matrix components in which amelogenins are the major proteins, the biochemical properties of which are well known. However, little is known about the characteristics of ameloblasts themselves or about the functions of amelogenins. In this study, we developed a novel primary and secondary culture system for ameloblasts using a monoclonal antibody which recognized amelogenin (En3). The cell layer on dentine removed from rat mandibular incisors was isolated and cultured in low calcium, serum-free medium. Primary culture was performed on collagen-coated culture plates and typically, two types of cells appeared. One major type changed morphology after the addition of a high concentration of calcium to the medium. Expression of amelogenin was shown as cytoplasmic particles in these cells using En3. In the secondary culture, expression of amelogenins was also observed. In this system, the cells grew and maintained the expression of amelogenin for about 3 weeks. PMID- 1458345 TI - Factors affecting the future need for dental manpower in Canada and Quebec. AB - During the past decade, dental faculties in North America have reduced class sizes due to a perceived oversupply of dentists. Several schools have been closed outright, and others have been threatened with closure. These actions may have a negative impact on the future supply of dentists. The current beliefs with regards to the oversupply of dentists have inadequately accounted for the dramatic demographic and epidemiologic changes that are occurring in North America. Major changes in population distribution and disease trends point to an increased need for adult dental services in the future. Therefore, models for dental manpower needs should integrate these data to avoid a potential shortage of dental health care personnel in the future. PMID- 1458346 TI - [Clinical characteristics affecting the need for relining of class 1 and class 2 removable mandibular prostheses]. AB - This study attempts to identify, from a sample of people wearing a class 1 or 2 removable prosthetic device on the lower jaw, the extent of the relining needs for these prostheses and their determining factors. Epidemiological methods were used to solve this problem. The relining needs increase with the amount of time elapsed since the prosthetic device was put in the mouth (p = 0.014). As for the other factors reviewed, i.e. class of device, type of retainers used, and occlusion, the authors have identified trends instead of real risk factors, since the impact of this study was significantly reduced due to the small number of people we were able to recruit. It was not always possible, therefore, to verify the statistical meaning of the associations observed. In clinical practice, the treatment plan should include a periodical evaluation of the relining needs. As it is now impossible to establish the approximate time when a prosthetic device may need relining, patients wearing one should be examined periodically and regularly. PMID- 1458347 TI - Magic disillusion. PMID- 1458348 TI - AIDS patient's discrimination appeal denied. PMID- 1458351 TI - Amalgam fees. PMID- 1458349 TI - Procera: a new concept in crown and bridge. PMID- 1458352 TI - Infection control. PMID- 1458353 TI - Infection control. PMID- 1458354 TI - Infection control. PMID- 1458355 TI - Leadership: the essential ingredient for practice success. PMID- 1458356 TI - Does HIV cause AIDS? A review. AB - It would require a detailed knowledge of virology, molecular biology, epidemiology, clinical medicine and politics, to appropriately compare and contrast the hypotheses on the causes of AIDS. The purpose of this review was not to do that, but to inform colleagues that alternative etiologies for AIDS have been considered. No doubt, this healthy questioning will continue until it has been demonstrated--via controlled studies of high-risk groups (both HIV positive and negative), matched for all other characteristics--that only those individuals with HIV positivity actually develop AIDS. It cannot be denied that a common theme to the hypotheses is the presence of high-risk activities. This has been used against the risk-AIDS hypothesis. How, for example, could it explain babies born with immunodeficiencies, K. Bergalis contacting AIDS from her dentist, the British nurse who died of AIDS after contracting HIV from her husband, or AIDS in the wives of hemophiliacs? It may be that these people died of specific diseases (leukemia, pneumonia, infections), which 20 years ago would have been diagnosed as such. Now, because these individuals are found to be HIV positive, they are viewed as AIDS patients. Alternatively, they may not have been asked about their nutritional status, use of psychoactive drugs, and immunosuppressive sexual practices. Additionally, it is possible that by the time AIDS was diagnosed they may have already received numerous antibiotic (immunosuppressive) drug treatments. In North America, for whatever reason, AIDS is associated with high risk groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458357 TI - The teaching of geriatric dentistry in Canada. AB - Very little is known about the current status of geriatric training programs at Canadian universities because of the scarcity of information published on the subject. A study of the geriatric dentistry training programs offered by Canada's 10 dental schools has been completed. Its intent was to determine what type of educational activities in geriatric dentistry have either been offered in the past, are being offered now, will be offered in the next academic year, or are planned for the next five years. The results indicate that the 10 schools are doing very little in this regard. To keep pace with the level of geriatric dentistry training currently being offered in the United States, the dental profession must convince Canadian faculty members that the teaching of geriatric dentistry is crucial to both the undergraduate student and the graduate dentist. Continuing education in geriatric dentistry could be used to meet the oral health needs of our frail and dependent senior citizens. Geriatric dentistry must be taught at all levels of the profession so that this special clientele can receive the necessary treatment either within or outside of the dental office. PMID- 1458358 TI - Denture identification: the University of Manitoba's denture identification service. PMID- 1458359 TI - Surface disinfection of saliva-contaminated dental X-ray film packets. AB - A study was undertaken to determine the most effective method for the surface disinfection of saliva-contaminated dental X-ray film packets. Size 2 Kodak Poly Soft film packets were placed in the oral cavities of patients and "sham" irradiated. After removal from the oral cavity, some of these packets were left untreated before being placed in transfer vials containing transport medium. Other packets were handled in one of three different ways before being placed in the transfer vials: 1) wiped with a piece of sterile tissue paper to remove visible saliva; 2) wiped once with a sterile piece of gauze soaked with disinfectant and then immediately wiped dry with a piece of tissue paper ("one wipe" surface-disinfection technique); or, 3) wiped twice with a sterile piece of gauze soaked with disinfectant and allowed to air dry ("two-wipe" surface disinfection technique). The transport medium was serially diluted and microbiological processing completed to obtain bacterial counts corresponding to the levels of bacterial contamination of the film packet surfaces. The two-wipe surface-disinfection method effectively eliminated bacterial contamination of the film packets, with all of the disinfectants tested being equally effective. The one-wipe technique, using disinfectant, appeared to be slightly less effective. Mere physical removal of the saliva from the film packet, without the use of disinfectant, was the least effective method. PMID- 1458360 TI - [Risks and benefits of removal of impacted third molars: critical review of the literature. 1]. AB - Because of the ever-increasing enthusiasm that new graduates have demonstrated for practising minor oral surgery procedures, the authors believed that it would be useful to translate the results of a research project done in 1990 by Drs. David S. Precious and Paul Mercier, who are well-known oral and maxillofacial surgeons. This paper is about the risks and benefits associated with the removal of impacted third molars. PMID- 1458361 TI - Monitoring nursing productivity: a unique approach integrating an on-line kardex with workload measurement. PMID- 1458362 TI - Consider becoming a computer lab coordinator. PMID- 1458363 TI - Evaluating the appropriateness of a nurse expert system's patient assessment. AB - The Urological Nursing Information System (UNIS) is an expert-system prototype designed to help nurses perform patient assessments on elderly nursing home residents known to be incontinent of urine. A study was conducted to evaluate the appropriateness of the patient-assessment parameters stored in the knowledge base of UNIS. These parameters were stored as objects--a kind of template for holding related clusters of data, facts, rules, hypotheses, or any knowledge in a single conceptual unit. Each object was rated for its appropriateness by 14 nurse experts. Resulting scores ranged from +14 to -14. The effect of the nurse experts' educational backgrounds and work settings on their ratings were also analyzed. The results indicated that 95.6% of the objects received favorable ratings from the nurse experts. Educational background was not a significant factor chi 2 = 5.2, but work settings did have a significant affect chi 2 = 21.07, p = 0.01. PMID- 1458364 TI - The nursing case management computerized system: meeting the challenge of health care delivery through technology. AB - Does nursing case management compute? In this article, the author attempts to explain how computerizing the team plan of care and critical pathways decreases paperwork, makes it easier to develop standardized team care plans, enhances quality improvement trending, and is flexible enough to update the plan of care according to the patient's changing needs. The Nurse Case Management Computerized System puts the patient care team plan into an interactive computer program. The computer does the work of presenting the nurse with care plan options and printing a hard copy ready to implement. Use of the computer program enhances the health care team's ability to individualize the team plan of care while maintaining patient care standards. The system is also used to collect patient care data automatically and to trend for quality improvement. PMID- 1458365 TI - Use of the nursing minimum data set. AB - The purpose of this study was to obtain information about usage of the Nursing Minimum Data Set (NMDS). Forty-six individuals (44%) who requested the NMDS Data Collection Manual responded to a mailed questionnaire. Most respondents reported actually using the Manual to educate other nurses or to structure nursing documentation. More than one third of the respondents used all of the elements within the NMDS, but the majority used, or intended to use, the elements in the Nursing Care category. The majority of NMDS elements that were being used, or intended to be used, were available from handwritten patient records. The NMDS elements had been recorded on an ongoing basis by 86% of the respondents, but only 31% could retrieve readily all of the elements. Implications for access to comparable, minimum nursing care and resources data are discussed. PMID- 1458366 TI - Implementing computer simulations as a strategy for evaluating decision-making skills of nursing students. AB - This article describes the implementation of a computer assisted instruction clinical simulation, as an evaluation strategy for determining baccalaureate students' clinical decision-making skills. Students' reactions toward this strategy have been consistently positive. Similarly, faculty were satisfied with this method of assessment. Our experience has convinced us that computer simulation is an objective, efficacious, and pragmatic method for measuring students' clinical decision-making skills. PMID- 1458367 TI - Some nutritional requirements of a mixed culture transforming Reichstein's compound S into prednisolone. AB - Reichstein's compound S was successfully converted to prednisolone in a single step fermentation using a mixed culture of Curvularia lunata and Mycobacterium smegmatis. Introducing additional medium at the time of bacterial inoculation and increasing the M. smegmatis inoculum to 8% were necessary for maximal dehydrogenation of cortisol to prednisolone (86%). However, beef extract, corn steep solids, and malt extract were inhibitory to the dehydrogenase activity and stimulatory to hydroxylase. Of the vitamins tested, nicotinic acid and riboflavin at 0.2 and 1.13 mg/L, respectively, resulted in maximum transformation of Reichstein's compound S (100%) and optimized prednisolone yields (92%) in the mixed culture. The trace elements present in the medium were sufficient for maximal transformation, and there was no need for an exogenous supply. Addition of ATP, sodium acetate, and NAD inhibited the dehydrogenation reaction. PMID- 1458368 TI - Regulation of alpha-aminoadipate reductase from Penicillium chrysogenum in relation to the flux from alpha-aminoadipate into penicillin biosynthesis. AB - The activity and regulation of alpha-aminoadipate reductase in three Penicillium chrysogenum strains (Q176, D6/1014/A, and P2), producing different amounts of penicillin, were studied. The enzyme exhibited decreasing affinity for alpha aminoadipate with increasing capacity of the respective strain to produce penicillin. The enzyme from all three strains was inhibited by L-lysine, and the enzyme from the lowest producer, Q176, was least sensitive. Between pH 7.5 and 6.5, inhibition of alpha-aminoadipate reductase by L-lysine was pH dependent, being more pronounced at lower pH. The highest producer strain, P2, displayed the lowest alpha-aminoadipate reductase activity at pH 7.0. In Q176, the addition of 0.5-1 mM of exogenous lysine stimulated penicillin formation, whereas the same concentration was ineffective or inhibitory with strains D6/1014/A and P2. The addition of higher (up to 5 mM) lysine concentrations inhibited penicillin production in all three strains. In mutants of P. chrysogenum D6/1014/A, selected for resistance to 20 mM alpha-aminoadipate, highest penicillin production was observed in those strains whose alpha-aminoadipate reductase was most strongly inhibited by L-lysine. The results support the conclusion that the in vivo activity of alpha-aminoadipate reductase from superior penicillin producer strains of P. chrysogenum is more strongly inhibited by lysine, and that this is related to their ability to accumulate increased amounts of alpha-aminoadipate, and hence penicillin. PMID- 1458369 TI - Sporulation of Streptomyces antibioticus ETHZ 7451 in submerged culture. AB - Streptomyces antibioticus ETHZ 7451 formed spores in cultures grown in a liquid medium from either a spore or a mycelium inoculum. The spores formed were similar to those formed on surface-grown cultures, except for reduced heat resistance. Both types of spores were sensitive to lysozyme, which is unusual for Streptomyces spores. Glucose and other carbon sources, which promoted different growth rates, did not affect sporulation efficiency. Nitrogen sources, such as casamino acids, that allowed high growth rates suppressed the sporulation. A remarkable repression was also observed in media with some nitrogen sources that promoted noticeably lower growth rates. In permissive media, with nitrogen sources that permitted relatively high growth rates, sporulation was conditioned to the consumption of ammonium in the medium, but not to that of other nitrogen sources, such as asparagine. Phosphate did not show a repressive effect on sporulation in the assayed conditions. PMID- 1458370 TI - Prevention of 5-fluorouracil-induced infection with indigenous Escherichia coli in tumor-bearing mice by nonspecific immunostimulation. AB - We have previously reported that the lethal toxicity of 5-fluorouracil (5-FU) in specific-pathogen-free mice is due to an indigenous infection with Escherichia coli (K. Nomoto, T. Yokokura, Y. Yoshikai, et al. Can. J. Microbiol. 37:244-247, 1991). In the present study, we demonstrate that nonspecific immunostimulation augments host resistance against the lethal toxicity of 5-FU in tumor-bearing mice. Intravenous administration of a preparation of heat-killed Lactobacillus casei (LC 9018), a nonspecific immunostimulant, at a dose of 20 mg/kg to BALB/c mice augmented their resistance against the lethal toxicity of 5-FU if the preparation was injected into the mice 10-40 days before administration of 5-FU. Injection of LC 9018 into BALB/c mice bearing Meth A fibrosarcoma also enhanced their resistance against the lethality of 5-FU. Systemic infection with E. coli was induced in all of the 5-FU-treated tumor-bearing mice 10 days or more after administration of the drug at a lethal dose of 500 mg/kg, and it was accompanied by an overgrowth of the bacteria in the intestine. Treatment of tumor-bearing mice with LC 9018 resulted in decreased rates of occurrence of systemic infection with E. coli and inhibition of overgrowth of the bacteria in the intestine after administration of 5-FU. A single administration of either LC 9018 or 5-FU significantly inhibited the growth of Meth A cells in vivo, and a combined antitumor effect was shown in the mice treated with both 5-FU and LC 9018. PMID- 1458371 TI - Pectin decomposition and associated nitrogen fixation by mixed cultures of Azospirillum and Bacillus species. AB - Cocultures of different Azospirillum species with Bacillus polymyxa or Bacillus subtilis allow the efficient utilization of pectin as carbon and energy sources for nitrogen fixation. The nitrogenase activity obtained with cocultures was as high as 30-80 nmol C2H4 h-1 mL-1, a much higher value than that obtained with pure cultures of either Azospirillum (up to 13 nmol C2H4 h-1 mL-1) or B. polymyxa (up to 2 nmol C2H4 h-1 mL-1) alone. To establish to what extent each partner contributed to nitrogenase activity, acetylene reduction was assayed as a function of time and it was also measured on Azospirillum cultivated in the cultures filtrates of the Bacillus. The results suggested that the nitrogenase activity was mostly produced by Azospirillum. The nitrogenase activity occurred at the expense of the degradation and fermentation products of the pectin. The new pectinolytic species, Azospirillum irakense, utilized both degradation and fermentation products of pectin, whereas the nonpectinolytic strains (Azospirillum brasilense, Azospirillum lipoferum, Azospirillum amazonense) utilized only the fermentation products of pectin, including acetic and succinic acids. These cocultures can be considered as metabolic associations, where the Bacillus produces degradation and fermentation products of pectin, which can be used by Azospirillum species. PMID- 1458372 TI - Nonspecificity of the Anda A60-tb ELISA test for serodiagnosis of mycobacterial disease. AB - The conventional methods for the laboratory diagnosis of tuberculosis and other mycobacterial diseases are time consuming and beyond the scope of most of the small and medium-sized hospital facilities. Therefore, there has been considerable interest in the development of a serological method for the detection of antibodies against mycobacteria. We recently evaluated a commercially available ELISA test (Anda Biologicals, Strasbourg, France) that measures antibody levels to A60 antigen, a membrane glycoprotein that is found in most mycobacteria. Of the 123 patients with positive pulmonary cultures for Mycobacterium tuberculosis, 82% had detectable antibodies against the kit antigen. Of the 68 patients with extrapulmonary tuberculosis, 59% yielded positive results. Specimens from 2 of the 12 patients that grew Mycobacterium avium-intracellulare complex, and one each with Mycobacterium fortuitum and Mycobacterium chelonei, were considered significant on the basis of medical history and repeated isolation of the bacterium from clinical specimens, and these patients yielded positive serology. Of the healthy, normal PPD positive and PPD negative controls, 24% gave false positive results. PMID- 1458373 TI - Interactive effects of salt concentration and temperature on growth and lipid composition in the moderately halophilic bacterium Vibrio costicola. AB - The interactive effects of NaCl concentration and growth temperature on the growth and lipid composition of the moderately halophilic eubacterium Vibrio costicola have been investigated. Vibrio costicola was shown to be capable of growth over the temperature range 4-37 degrees C. Maximum growth yields were obtained at 30 degrees C when the optimum NaCl concentration was 1.0 M NaCl. In contrast with some previous studies, at higher or lower growth temperatures both the optimum and lower limit of NaCl concentration were higher, but there was no change in the upper limit of NaCl concentration for growth. There were no differences between the lipid compositions of cultures grown in 1 M NaCl at 30 or 37 degrees C, but as the growth temperature was lowered from 30 to 10 or 4 degrees C, the ratio of phosphatidylethanolamine to phosphatidylglycerol increased significantly as a result of the conversion of phosphatidylglycerol to diphosphatidylglycerol; in addition, at the lower growth temperatures the phospholipid fatty acyl composition became more unsaturated and the mean acyl chain length was shorter. It is suggested that the altered salt dependence of V. costicola at temperatures below the optimum for growth is due to a modification in membrane lipid phase behavior and stability brought about by changes in lipid composition, whereas a different mechanism operates above the growth temperature optimum. PMID- 1458374 TI - A filamentous-like mutant of Listeria monocytogenes with reduced expression of a 60-kilodalton extracellular protein invades and grows in 3T6 and Caco-2 cells. AB - We describe a spontaneous rough mutant of Listeria monocytogenes that produces reduced amounts of a 60-kilodalton major extracellular polypeptide (p60) as shown by sodium dodecyl sulfate--polyacrylamide gel electrophoresis and Western blot analysis. The cells of this mutant are filamentous, do not give rise to smooth wild-type colonies, and produce listeriolysin O in amounts equal to that of the wild-type cells, but they show a reduced virulence in the mouse LD50 model and in the Caco-2 tissue culture virulence assay. Light and electron microscopic studies show that this mutant invades and remains filamentous during in vivo growth in both Caco-2 and 3T6 tissue culture monolayers. The reduced virulence of the rough mutant is not due to the inability of its filamentous forms to invade or to grow in nonprofessional phagocytes since invasion and growth of the smooth wild-type and the rough mutants are comparable in both Caco-2 and 3T6 monolayers. PMID- 1458375 TI - Identification of Salmonella typhimurium invasiveness loci. AB - Salmonella typhimurium is capable of entering into (invading) nonphagocytic host cells. To systematically identify the bacterial genes necessary for this process, 15,000 Tn10dCm random transposon mutants of S. typhimurium were individually screened for invasiveness, using the human colonic epithelial Caco-2 cell line. Four hundred and eighty-eight mutants had decreased levels of invasiveness; most were nonmotile. However, five mutants, representing four loci, were completely motile. Further characterization of these five mutants showed that they were also unable to enter the dog kidney epithelial cell line MDCK and the mouse macrophage line J774.A1. In contrast to the parental strain, they were unable to disrupt the transepithelial resistance of polarized epithelial monolayers, nor were they able to penetrate across these epithelial barriers. Three of the four classes of mutants remained virulent in mice. The results confirm several aspects of S. typhimurium invasiveness: (i) intact motility enhances invasiveness of cultured cells; (ii) S. typhimurium invasiveness is multifactorial, and at least six distinct genetic loci are involved; and (iii) invasion loci involved in uptake into epithelial cells are also needed for uptake into cultured phagocytic cells. The results also emphasize that decreased levels of invasiveness eliminate bacterial penetration of polarized epithelial barriers and invasiveness loci mutants are not necessarily avirulent. PMID- 1458376 TI - DNA sequence heterogeneity in the gene encoding a 60-kilodalton extracellular protein of Listeria monocytogenes and other Listeria species. AB - Chromosomal DNA sequences from the 60 kilodalton protein gene of Listeria monocytogenes, amplified by the polymerase chain reaction, were used for restriction fragment length polymorphism differentiation of L. monocytogenes serotypes and other Listeria species. All 24 strains of L. monocytogenes examined produced an extracellular protein of molecular weight 60,000 (p60) as determined by Western blot analysis. Four of six other Listeria species had a protein that cross-reacted to antibodies to p60, but all differed in molecular weight, ranging from approximately 50,000 to 65,000. The gene encoding p60 was amplified from chromosomal DNA in all strains using polymerase chain reaction with a single primer pair. Restriction enzyme digestion with HindIII of the amplified product revealed a restriction pattern that was distinct between serotypes 1/2a and either 4b or 1/2b of L. monocytogenes. Of the other Listeria species, four strains that produced a cross-reacting protein likewise produced a polymerase chain reaction amplification product with the primer pair. Listeria innocua alone had a restriction pattern similar to that of Listeria monocytogenes serotype 4b and 1/2b. Genotypic heterogeneity, as revealed by DNA amplification and restriction endonuclease digestion of the p60 open reading frame, correlates with "electrophoretic type" grouping and may be related to differences in virulence mechanisms of Listeria monocytogenes and other Listeria species. PMID- 1458377 TI - [Changes in culture and biochemical characteristics of Salmonella paratyphi B after incubation in seawater]. AB - After incubation in seawater Salmonella paratyphi B cells rapidly became unable to grow on bacteriological media. Previous adaptation to high osmolarity conditions greatly slowed down this process. Strains isolated from seawater microcosms after varying incubation periods were qualitatively different and showed changes in some of their growth (colony shape and size) and biochemical properties (acidification of some sugars, gelatinase activity, acetoin production, nitrate reduction). Because of these modifications, the bacteria showed atypical profiles and could not be identified as members of the Salmonella genus. The alteration of the phenotype, although reversible, could explain some of the false-negative results obtained upon isolation and identification of these bacteria in seawater samples. PMID- 1458378 TI - Laparoscopic cholecystectomy: the six hemoclip rule. PMID- 1458379 TI - Treatment for nonunion of humeral shaft fractures. PMID- 1458380 TI - Routine nasogastric decompression after abdominal surgery? PMID- 1458381 TI - An unusual case of hemoperitoneum due to forgotten blunt trauma. PMID- 1458382 TI - Goodbye to routine. PMID- 1458383 TI - Choledochal cysts: a retrospective review of 28 patients and a review of the literature. AB - Retained choledochal cysts have been associated with recurrent cholangitis, portal hypertension and malignant lesions of the biliary tract. The authors reviewed the cases of 23 females and 5 males who had congenital cystic dilatation of the biliary tree; 26 were seen primarily and 2 were referred because of complications from previous surgery. Patient age at presentation ranged from 6 weeks to 46 years. The presenting complaints in 25 patients were pain or jaundice, or both; the classic triad of pain, jaundice and an abdominal mass was present in only 3 patients. Primary cyst excision was performed in 11 patients. Internal drainage procedures were performed in 12 patients, external drainage procedures in 3 patients and no direct operative procedure in 2 patients. Follow up ranged from 1 to 20 years. Nine of 11 patients with primary excision were asymptomatic; 2 had recurrent cholangitis and required treatment for bile duct stricture. Five patients with retained cysts were asymptomatic. Recurrent cholangitis occurred in seven patients. Six patients required at least one reoperation, but only two had secondary cyst excision. The long-term complication rate for patients with retained cysts was 66.7% and for those with primary excision was 18%. The findings of this study support the current recommendation of primary excision of choledochal cysts. Symptomatic patients with retained cysts should have secondary cyst excision. Asymptomatic patients with retained cysts are at risk for malignancy and should undergo lifelong periodic radiologic examinations and liver-function testing. PMID- 1458384 TI - Primary cutaneous malignant melanoma: experience of the British Columbia Cancer Agency from 1972 to 1981. AB - A retrospective review of 891 patients with newly diagnosed primary cutaneous malignant melanoma (CMM) registered at the British Columbia Cancer Agency from 1972 to 1981 is presented. Age-standardized incidence rates in British Columbia have increased markedly over that time. The female-to-male ratio was 1.13:1 and the median age overall was 47 years. A change in the size of a mole was the most common presenting sign (in 43% of patients) and the median duration of signs was 5.9 months. Predominant tumour sites were the trunk for males and the lower limbs for females. Dominant growth patterns were superficial spreading melanoma (65%), nodular melanoma (25%), lentigo maligna melanoma (5%) and acral lentiginous melanoma (2%). On staging of the primary tumour, 90% of patients had local disease, 9% of patients had regional disease and 1% of patients had distant disease at presentation. Median depths of tumours were 1.45 mm for males and 1.10 mm for females; no T1 tumours (tumours 0.75 mm or less in depth [TNM classification]) were staged beyond the local area. Disease recurred in 44% of males and 32% of females. The 15-year survival rate was 55.5% for males and 70.3% for females. These findings are compared with those of recent international series. It is apparent that earlier diagnosis improves survival and that more education is needed in view of the increasing incidence and death from CMM. PMID- 1458385 TI - Elective and therapeutic regional lymph node dissection for cutaneous malignant melanoma: experience of the British Columbia Cancer Agency, 1972 to 1981. AB - The authors present a 10-year review of patients registered at the British Columbia Cancer Agency (BCCA) who underwent lymph node dissection for malignant melanoma. Pathological findings in the regional lymph nodes were correlated with primary site, growth pattern, depth of invasion and Clark's level. Elective lymph node dissection (ELND) was performed in 223 patients, and the overall positivity rate (pathologically involved nodes) was 16%. Survival rates for patients who had ELND were compared with those for BCCA patients not having had ELND and patients from the University of Sydney, Sydney, Australia. Although patients who underwent ELND had thicker and more frequently ulcerated primary tumours than patients with stage I disease who did not undergo ELND, survival was better in the group who had ELND. However, when all potential prognostic factors were analysed by multivariate analysis, ELND was not a significant factor in prognosis. Therapeutic lymph node dissection (TLND) was performed in 50 patients at the time the primary tumour was diagnosed, and involvement of the lymph nodes was found in 36. Of 525 patients with clinical stage I disease who did not have ELND, disease recurred in the regional lymph nodes in 119; 86 of them had TLND for recurrence (RTLND). Median survival rates from the time of diagnosis of the primary lesion for ELND-positive, TLND-positive and RTLND patients were 4.2, 2.7 and 4.4 years respectively; the differences were not significant. New treatments are required for patients with involved regional lymph nodes. PMID- 1458386 TI - Clinical performance of the Duromedics bileaflet pyrolite mechanical prosthesis. AB - The Duromedics (Baxter Healthcare Corp., Edwards CVS Div., Irvine, Calif.) mechanical cardiac valvular prosthesis was implanted in 480 patients between 1984 and 1987 at the Montreal Heart Institute, the Hospital Clinic of Barcelona and the teaching hospitals of the University of British Columbia. The mean age of the patients was 52 years. The early mortality was 7.9% and the late mortality was 4.1% per patient-year. The overall survival at 4 years for aortic valve replacement (AVR) was 87.0% +/- 3.7% and for mitral valve replacement (MVR) was 81.9% +/- 2.9%. There were 16 valve-related reoperations in 14 patients--for prosthetic valve endocarditis in 9 patients, for thromboembolism in 1 patient and for nonstructural dysfunction in 4 patients. The freedom from thromboembolism at 3 and 4 years was 94.3% +/- 3.1% for AVR and 95.1% +/- 1.8% for MVR. The freedom from prosthetic valve endocarditis at 3 and 4 years was 95.3% +/- 2.2% for AVR and 96.2% +/- 1.6% for MVR. The freedom from structural valve deterioration for all positions was 100%. The freedom from reoperation at 4 years was 95.3% +/- 2.1% for AVR and 92.3% +/- 4.3% for MVR and from valve-related death was 98.7% +/ 1.3% for AVR and 96.2% +/- 1.6% for MVR. The freedom from all valve-related complications at 4 years was 87.7% +/- 3.8% for AVR and 85.7% +/- 2.9% for MVR. Long-term evaluation of the Duromedics prosthesis is required to determine the influence of documented structural valve deterioration. PMID- 1458387 TI - Acute mesenteric ischemia: an aggressive diagnostic and therapeutic approach. 1991 Roussel Lecture. AB - The incidence of acute mesenteric ischemia (AMI) has increased substantially over the last few decades. Death rates of 70% to 90% have been reported for traditional methods of diagnosis and therapy. Use of an aggressive radiologic, pharmacologic and surgical approach has decreased the mortality and morbidity associated with AMI. The cornerstones of management are prompt diagnosis by the earlier and more liberal use of angiography and the incorporation of intra arterial papaverine in the treatment of both occlusive and nonocclusive AMI. Widespread adoption of this protocol in patients at risk might improve the overall results of treatment of AMI. PMID- 1458388 TI - Routine omission of nasogastric intubation after gastrointestinal surgery. AB - The need for routine nasogastric-tube decompression after gastrointestinal surgery has been challenged repeatedly for several years. To determine whether nasogastric intubation can be omitted routinely, 101 consecutive patients who underwent gastrointestinal surgery were managed prospectively without nasogastric tubes. Excluded were patients with complete bowel obstruction and those who required prolonged endotracheal intubation. These patients were compared with 101 retrospective controls who had nasogastric decompression routinely. There were four protocol violations in the prospective group (nasogastric tubes were left in place postoperatively) and one in the retrospective group (no nasogastric tube postoperatively), leaving 97 and 100 patients, respectively, for follow-up. The mean duration of hospitalization in comparable patients was 10.6 days in patients without decompression and 11.9 days in those with routine decompression. Subsequent nasogastric-tube insertion was required in nine patients who did not undergo routine decompression, compared with two patients who had routine decompression. There were no statistically significant differences in the rates of anastomotic leaks, wound disruptions and pulmonary or other complications between the two groups. The authors conclude that nasogastric decompression can be safely omitted as a routine part of postoperative care after gastrointestinal surgery. PMID- 1458389 TI - A prospective randomized trial of routine postoperative nasogastric decompression in patients with bowel anastomosis. AB - Until relatively recently, the nasogastric (NG) tube has been used routinely for decompression in the patient with small- or large-bowel anastomosis. To determine if routine postoperative NG decompression benefited such patients, 102 patients were randomized prospectively to either NG decompression or no-NG tube. Excluded were patients with chronic bowel obstruction, peritonitis, gross fecal contamination or spillage, and previous abdominal or pelvic irradiation. There were 52 patients in the no-NG group and 50 in the NG group. Patients in the no-NG group had earlier bowel sounds, return of flatus, oral intake and first bowel movement. Four patients (8%) in the no-NG group, compared with one patient (2%) in the NG group, required subsequent decompression. Length of hospital stay was significantly (p < 0.001) shorter in the no-NG group. There were no significant differences in the presence of atelectasis, postoperative fever, wound infections and anastomotic leaks between the two groups. The authors conclude that routine nasogastric decompression is not warranted after elective surgery involving small or large-bowel anastomosis. PMID- 1458390 TI - Renal perfusion with the Biomedicus pump during resection of an abdominal aortic aneurysm. AB - Renal artery perfusion is usually unnecessary during resection of an abdominal aortic aneurysm, because most of these aneurysms are situated below the renal arteries. The authors report the interesting case of a patient with a solitary functioning kidney, who had undergone previous bypass grafting from the right iliac artery to the right renal artery and in whom the kidney was perfused with the Biomedicus pump during the repair of an abdominal aortic aneurysm. This technique may be useful in special situations in which any period of renal ischemia might be hazardous to renal function. PMID- 1458391 TI - Reconstruction of avulsed scalp after go-cart injury. AB - Scalp avulsion is a rare injury that has significant physical and psychological consequences. It may require emergency replantation or late, challenging surgical reconstruction, or both. The authors describe two patients who had scalp avulsion. Each patient got long hair entangled in the uncovered engine of a go cart. One underwent unsuccessful replantation without vascular repair; the other had a large segment of scalp successfully replanted with microvascular repair. Both patients required late reconstruction with tissue expansion. The final results were good. When feasible, microvascular replantation is the treatment of choice. If replantation is not possible, temporary cover by skin grafts followed by later reconstruction with tissue expansion can be effective. PMID- 1458392 TI - Injuries to the nervous system and spine in downhill skiing. AB - The authors describe injuries to the nervous system and spine from downhill skiing accidents through a review of the charts of downhill skiers admitted over 5 years to the three teaching hospitals of the University of Calgary. The office of the chief medical examiner provided details about accidental deaths from downhill skiing in which nervous system trauma occurred. During the study period, 145 downhill skiers suffered injury to the nervous system or spine. There were five deaths from nervous system trauma. The mean age of the injured skiers was 23.8 years, and these injuries were three times more common in men than in women. Eighty-eight skiers sustained a head injury, 25 had spinal fractures alone, 20 had spinal cord or nerve root injury and 12 had peripheral nerve injury. A simple fall on the hill was the commonest method of injury, followed in frequency by collision with a tree, which caused the most severe injuries. Reckless skiing, design of ski runs and man-made snow were contributing factors. The serious nature and number of these injuries must be recognized, and further study is needed on causal factors and preventive measures. PMID- 1458393 TI - Splenic vein thrombosis as a cause of variceal bleeding. AB - Splenic vein thrombosis as a cause of variceal bleeding is underdiagnosed. Newer, noninvasive techniques of diagnosis that have been introduced recently appear to be accurate. Isolated gastric varices in the presence of normal liver function and especially in the presence of pancreatic disease should prompt a search for splenic vein thrombosis. Splenectomy is the treatment of choice. PMID- 1458394 TI - Major vessel excision in retroperitoneal lymph node dissection. AB - Retroperitoneal malignant tumours, both primary and metastatic, may involve surrounding structures such as the aorta and vena cava, making complete tumour excision difficult. En bloc resection of major blood vessels should be considered in such cases. The authors describe three patients who underwent excision of major blood vessels with retroperitoneal lymph node dissection. Two patients had aortic resection with placement of a Dacron tube graft, and one had excision of the vena cava from above the renal vessels to the level of the common iliac veins with distal venous ligation. The low complication rate confirms the feasibility of excising major blood vessels to accomplish complete retroperitoneal lymphadenectomy. PMID- 1458395 TI - Blunt traumatic avulsion of an intercostal artery: an unusual case of thoracic aortic injury. AB - The aortic isthmus is the most commonly injured part of the thoracic aorta in patients who survive blunt deceleration injury to that vessel long enough to reach a hospital. Occasionally, avulsion of the brachiocephalic arteries from the aortic arch is seen. The authors describe an unusual form of intrathoracic vascular injury in which mediastinal hemorrhage occurred secondary to avulsion of an intercostal artery from the descending thoracic aorta as a result of a vertical deceleration injury. PMID- 1458396 TI - Treatment for nonunion of the shaft of the humerus: comparison of plates and Seidel interlocking nails. AB - From July 1986 to November 1989, fractures of the humeral shaft in 35 adults who had nonunion of the fracture were managed by plate fixation (19 patients) or antegrade nailing of the fracture fragments with the Seidel interlocking nail (16 patients) together with cancellous bone grafting. The follow-up period ranged from 12 to 52 months. Of the patients who had plate fixation, 89.5% had fracture union within 4.5 +/- 1.7 months; of the patients whose fracture was managed with the Seidel interlocking nail, 87.5% had fracture union within 4.4 +/- 1.8 months. The range of shoulder motion was improved with both techniques. Patients who had plate fixation had more complications than those whose fracture was managed by interlocking nailing (21% v. 12%). The authors prefer interlocking nailing because it is a relatively simpler technique, resulting in fewer complications. It may replace plating in the treatment of nonunion of humeral shaft fractures. However, rotatory instability with interlocking nailing cannot be disregarded, and if this is evident plate fixation should be done. PMID- 1458397 TI - Tobacco control boards? PMID- 1458398 TI - Why another examination? PMID- 1458399 TI - Why another examination? PMID- 1458400 TI - Why another examination? PMID- 1458401 TI - Why another examination? PMID- 1458402 TI - Exodus of Canadian physicians. PMID- 1458403 TI - Changes in the undergraduate medical curricula. PMID- 1458404 TI - Immunization of immigrants. PMID- 1458405 TI - Women can abuse too. PMID- 1458406 TI - Chlamydial infection in Canada. PMID- 1458407 TI - Physicians and the environment. PMID- 1458408 TI - Beta-carotene: potential anticarcinogen. PMID- 1458409 TI - Attention deficit disorder and food intolerance. PMID- 1458410 TI - Strike out flu! PMID- 1458411 TI - Steroid therapy. PMID- 1458412 TI - Nasogastric tube placement. PMID- 1458413 TI - Conflict of interest among researchers. PMID- 1458414 TI - Kaiser Permanente system. PMID- 1458416 TI - Physicians are not overpaid. PMID- 1458415 TI - Hospital mergers recommended for London, England. PMID- 1458417 TI - The most northerly practice in Canada. PMID- 1458418 TI - Improving epidemic control: lessons from the 1987 toxic mussels affair. PMID- 1458419 TI - Outcomes and the management of health care. Health Services Research Group. PMID- 1458420 TI - Guidelines for transfusion of erythrocytes to neonates and premature infants. Fetus and Newborn Committee, Canadian Paediatric Society. AB - The transfusion of erythrocytes to neonates and premature infants is common and should be minimized through a reduction in the number of blood samples taken for laboratory tests. The risks to patients have been minimized with current blood banking techniques, although neonates and premature infants may require special consideration. The indications for transfusion of erythrocytes to neonates include the presence of shock, a loss of 10% or more of the blood volume within 72 hours when further blood sampling is expected, a hemoglobin level of less than 130 g/L in neonates with cardio-respiratory disease who require increased oxygen carrying capacity, and a hemoglobin level of less than 80 to 100 g/L in neonates with tachypnea, tachycardia, recurrent apnea, poor feeding or failure to gain weight. The attending physician should consider these indications along with clinical judgement to ensure safe and effective erythrocyte transfusion. PMID- 1458421 TI - Rate of death from cervical cancer among native Indian women in British Columbia. AB - OBJECTIVE: To compare the rates of death from cervical cancer among native Indian women and non-native women in British Columbia from 1953 to 1984. DESIGN: Retrospective analysis of data retrieved from the British Columbia Division of Vital Statistics. MAIN OUTCOME MEASURES: Age-standardized death rate and relative rate. RESULTS: The rate of death from cervical cancer was significantly higher among the native women than among the non-native women throughout the study period. No deaths from cervical cancer were recorded in women under 20 years of age. Among those 20 to 64 the relative rate increased from 3.83 in 1953-62 to 6.53 in 1973-84; among those 65 or more it decreased slightly. For the entire study period the relative rate for women 20 to 64 years old was 5.95 and for those 65 or older 2.98. CONCLUSION: The rate of death from cervical cancer among native women in British Columbia is unacceptably high, probably because the provincial screening program does not reach as many native women as it does non native women. PMID- 1458422 TI - Underrecognition of chylomicronemia as a cause of acute pancreatitis. AB - OBJECTIVE: To determine how often chylomicronemia is considered by admitting physicians as a possible cause of acute pancreatitis. DESIGN: Retrospective hospital chart review. SETTING: Tertiary care teaching hospital in an urban centre with a referral population of 1 million. PATIENTS: All patients admitted with acute pancreatitis from Jan. 1, 1985, to Dec. 31, 1987. Episodes of pancreatitis were divided into two groups: those for which a cause was known after history taking, physical examination and laboratory investigation at the time of admission (group 1) and those for which a cause was unknown after full examination (group 2). RESULTS: There were 319 episodes of chylomicronemia in 162 patients. The cause of the pancreatitis was known after examination at the time of admission in 239 (75%) of the episodes; there was hypertriglyceridemia in 7 (3%). No cause was identified after examination in the other 80 episodes (25%); chylomicronemia was considered in 18 cases (29%) and was found in 6 (33%) of them (mean serum triglyceride level 34.4 mmol/L). Of the remaining 62 episodes in group 2, 10 (16%) were later found to be caused by chylomicronemia (mean serum triglyceride level 22.6 mmol/L). Among the 80 episodes in group 2 at least one medical condition associated with chylomicronemia was present in 24. In only 7 (29%) of the 24 was chylomicronemia considered; in 6 the mean serum triglyceride level was 19.7 mmol/L. CONCLUSIONS: Although the overall detection rate of chylomicronemia was low, its presence in patients without other etiologic factors after examination may have been much higher. Consideration of chylomicronemia in this subgroup at the time of presentation may increase diagnostic yield and help prevent further occurrences of pancreatitis. PMID- 1458423 TI - Hypoalphalipoproteinemia. PMID- 1458424 TI - Christmas 1982: religion, science and faith. 1982. PMID- 1458425 TI - Major antismoking moves proposed after navy survey points to smoking epidemic. PMID- 1458426 TI - Yellowknife MDs forced to deal with fallout from bitter strike, explosion. PMID- 1458427 TI - Night myopia may place many young drivers at risk, MD says. PMID- 1458428 TI - Is health technology assessment medicine's rising star? PMID- 1458429 TI - Move to pay more attention to women's issues sign of changing health care times in US. PMID- 1458430 TI - About that fee increase .... PMID- 1458431 TI - Supreme Court decision forces CMA to revise policy on patients' right to records. PMID- 1458432 TI - Selling services becoming increasingly important to bottom line, hospitals say. PMID- 1458433 TI - Ultrastructural localization of HIV-1 RNA and core proteins. Simultaneous visualization using double immunogold labelling after in situ hybridization and immunocytochemistry. AB - The analysis of human immunodeficiency virus type 1 (HIV-1) RNA sequences in CEM and Jurkat lymphoid cells infected with the virus has been performed at the subcellular level. Using a biotinylated DNA probe specific for HIV-1, virus RNA sequences were detected on Lowicryl thin sections after immunogold cytochemistry. The labelling observed on the cytoplasm was localized near the plasma membrane connected with extracellular cluster of virions. On free immature and nascent form of the virus the detection of HIV-1 RNA was associated with the peripheral electron-dense structure, whereas on mature form the labelling was concentrated on the central nucleoid known to be the site of the HIV-1 genomic RNA. The identification of virus RNA was also performed simultaneously with the detection of HIV-1 core protein p24 or p17 using a double immunogold labelling. Whereas the HIV-1 RNA showed again a cytoplasmic and virions localization, the structural protein was only observed on viral formations. The cytoplasmic localization of virus RNA, at the time of virus production, suggests that they are of genomic origin destined to be packaged in virions once the assembly of virus structural proteins has taken place in the plasma membrane at the viral budding site. The present molecular investigation conducted at the subcellular level provides insight into the cell periphery distribution of HIV-1 RNA observed at the light microscope as corresponding to the detection of HIV-1 infected lymphoid cells actually releasing virions. PMID- 1458434 TI - A study of peritoneal cells from healthy and Schistosoma mansoni-infected mice with special reference to myofibroblasts arising in culture. AB - Adherent, trypsin-resistant, peritoneal cells from mice with chronic schistosomiasis mansoni, and from control mice, were cultivated in vitro up to 20 days. Fibroblasts regularly appeared, about 6 days after seeding, in cultures of the manyfold more numerous cells from infected mice, concomitantly with a dramatic increase, detected by autoradiography, in the percentage of DNA replicating cells of the monocyte-macrophage lineage. Peritoneal cells from healthy and from infected mice were fractionated on discontinuous Percoll gradients. Eight cell subsets were harvested in both cases, quantitated, and studied by electron microscopy. Two fractions (2 and 3: 1.041 < densities < 1.060 g/ml) from infected mice were greatly enriched in monoblasts and promonocytes. The cells of the different subsets were seeded separately, trypsin-treated and cultivated in vitro. Cultures of cell fractions 2 and 3 from infected mice contained the majority of the DNA-synthesizing cells and gave regularly rise to fibroblasts. Cultures of the different fractions were used for sequential morphological observations (2-11 days) at the electron microscope level. Early cultures were also used for the ultrastructural detection of the Mac-1 (CD 18/CD 11b) surface antigen by gold immunocytochemistry. A few fibroblasts were rarely observed in cultures of fractions 2 and 3 from control mice, while cells with ultrastructural features of myofibroblasts were regularly observed in cultures of the same fractions harvested from mice with chronic schistosomiasis. Fractions 2 and 3 from infected mice contained a large number of Mac-1 positive monoblasts. The correlations between the presence of monoblasts, DNA replication in cells of the monocyte-macrophage lineage and the appearance of myofibroblasts in cultures of the same fractions derived from infected mice are discussed. PMID- 1458435 TI - A mouse repeat sequence conserved in eukaryotic genomes. AB - To study the biological role of simple repetitive DNA sequences, we analysed a clone isolated from a mouse macrophage cDNA library called T2. This clone contains two simple repetitive sequences: a new sequence, 'CAGAGAGG', and a sequence previously described, 'GATA'. By sequencing analysis, an open reading frame, coding for 225 amino acids, is detected in the T2 clone. The new simple sequence is present thousands of time in the mouse genome, associated or not with the sequence 'GATA'. The sequence 'CAGAGAGG' is transcribed in messenger RNAs. Northern blots of RNAs extracted from adult tissues and from differentiated or non differentiated cell lines show a large number of transcripts that quantitatively decrease when in vitro differentiation occurs. Moreover, Southern blots of DNA extracted from different organisms, hybridize with a fragment containing only the 'CAGAGAGG' sequence, demonstrating that this sequence is represented in the genome of phylogenetically distant eukaryotes, and is highly conserved during eukaryotic evolution. PMID- 1458436 TI - Ultrastructure of cilia in horses. AB - This paper presents some ultrastructural details of cilia from the ciliated tracheal epithelium of healthy horses. By using a new fixation method, the Authors were able to describe minute details, some of which have been only rarely observed in other species and mostly by means of the freeze-etch technique (i.e. electron dense particles of ciliary necklace). The Authors justify the need to investigate the ultrastructural details of cilia in various species since the minute morphological differences might be functionally significant. PMID- 1458437 TI - Reorganization of the Golgi complex in association with mitosis: redistribution of mannosidase II to the endoplasmic reticulum and effects of brefeldin A. AB - Previous studies have shown that the Golgi complex is broken down into dispersed clusters of vesiculotubular elements as mammalian cells enter mitosis and is reformed in each daughter cell in telophase/cytokinesis. In the present investigation, mannosidase II (a membrane-bound enzyme involved in oligosaccharide processing) was used as a marker to explore the fate of the Golgi complex in dividing L929 and CHO cells in some additional detail. Immunofluorescence microscopy demonstrated a juxta- or perinuclear staining for mannosidase II (man II) in interphase and immunoelectron microscopy revealed that it was restricted to the stacked Golgi cisternae at this stage. As the cells entered mitosis, the staining for man II assumed a pattern of dispersed elements in prophase and then turned into a diffuse pattern during metaphase and anaphase. At the electron microscopic level, this corresponded to a successive disorganization of the Golgi complex, first into structurally modified stacks scattered throughout the cytoplasm, and thereafter into small clusters of vesicles and tubules. In parallel, most of the immunoreactivity for man II was shifted into partially fragmented cisternae of endoplasmic reticulum, and only small amounts were found in the clusters just mentioned. During telophase/cytokinesis a circumscribed staining for man II reappeared in each daughter cell. At the electron microscopic level, cisternal stacks positive for man II were found to reform at the same time as immunoreactivity disappeared from the endoplasmic reticulum. Typically, the Golgi region was first located on the proximal side of the nucleus as related to the intercellular bridge, and then moved to the distal side of the nucleus before the cells were about to separate. Treatment of synchronized mitotic cells with brefeldin A, a fungal metabolite that inhibits endoplasmic reticulum to Golgi transport, prevented reformation of the Golgi complex in telophase/cytokinesis. Nevertheless, the separation of the daughter cells was completed at a similar rate as in the controls. On the basis of these findings, an extended model of the disorganization and reorganization of the Golgi complex in association with mitosis is presented. According to this model the disorganization of the Golgi complex at the onset of mitosis is a two step process: the Golgi stacks are first separated from each other and spread out in the cytoplasm; thereafter the Golgi stacks disintegrate, at least in part by return of Golgi components to the endoplasmic reticulum. In interphase cells, similar changes in the organization of the Golgi complex are produced by microtubule-disruptive drugs (dispersion of the stacks) and brefeldin A (redistribution of Golgi proteins into the endoplasmic reticulum), respectively. PMID- 1458438 TI - Ultrastructural analysis of differentiation of rat endoderm in vitro. Adipose vascular-stromal cells induce endoderm differentiation, which in turn induces differentiation of the vascular-stromal cells into chondrocytes. AB - Isolated definitive endoderm from 9-day-old rat embryos was cultivated up to 24 days in plastic and glass petri dishes and on developing vascular-stromal cells (mesenchymal cells) from epididymal white and interscapular brown adipose tissue of 4-week-old male rats. Explants were analyzed histologically and ultrastructurally. Endoderm attached to the bottom of the glass or petri dishes degenerated under one week of cultivation. Endoderm free floating in the culture medium developed into unilaminar vesicles whose flat epithelium did not differentiate. However, endoderm inoculated on developing mesenchymal cells differentiated into glandular explants or into ciliated pseudostratified columnar respiratory epithelium. The glandular explants were made up of at least four different kinds of cells whose cytoplasm showed predominantly: a) polyribosomes, b) lysosomes, c) mitochondria or d) cytoskeletal filaments. Endodermal cells differentiated only if, during cultivation, they were in contact with or in close proximity to developing mesenchymal cells. Endoderm differentiating into the respiratory epithelium in turn directed differentiation of the underlying vascular-stromal cells into lamina propria cells and chondrocytes. Cultivated vascular-stromal cells in the upper layers became thicker, ellipsoid in shape and with enlarged intercellular space. They appeared to be lamina propria cells and, together with the respiratory epithelium, built folds of respiratory mucosa. The vascular-stromal cells in the layers close to the bottom developed into chondrocytes; i.e., the cells became oval and agglomerated in nest like structures with a defined extracellular matrix. Their cytoplasm contained abundant cisternae of rough endoplasmic reticulum and numerous vacuoles with PAS positive substance. These observations showed that even developing vascular stromal cells from adipose tissue from postlactating rats can trigger the process of definitive endoderm differentiation. Once triggered, differentiating endoderm influenced differentiation of the vascular-stromal cells into the cells and tissues of a wall of the respiratory tract. PMID- 1458439 TI - The effect of thyrotropic hormone (TSH) on the thyroid gland of the newborn rat. An electron microscopic study. AB - The activity of the thyroid gland of the newborn rat is influenced by the treatment of TSH. Shortly after hormone injection, its effects can be detected in the synthesis and storage of the colloid. In a longer term (30 min and 60 min) the morphological signs of resorption and secretion are evident. At this early age the cellular compartments involved in the secretory pathway of the cells are still not complete in maturation (less developed Golgi complex, missing secretory vesicles and micropinocytotic vesicles). According to our results, even TSH administration cannot influence this picture in the short term. Our work supports the intracellular way of folliculogenesis, and the TSH action as a promoter in this way. PMID- 1458441 TI - Conventional and high resolution scanning electron microscopy of outer and inner surface features of cerebellar nerve cells. AB - This paper provides an exploration into the inner and outer surfaces of vertebrate cerebellar neurons utilizing secondary electron (SE-I and SE-II) topographic contrasts. SE-I enriched chromium coated, cryofractured Rhesus monkey cerebellum staged within the condenser/objective stage of SEMs equipped with high brightness LaB6 and field emission emitters generated quality images of intact and fractured nerve cells studied at intermediate and high magnifications. These images were compared with conventional SE-III images of gold-palladium teleost fish cerebellar neurons and transmission electron micrographs of mouse cerebellar nerve cells obtained either by thin-sections or freeze-etch replicas. Chromium coated Rhesus monkey granule and Golgi cell surfaces revealed smooth, accurately delineated profiles of true cell surface features, which lacked the SE-III dominated brilliance of conventional teleost fish gold or gold-palladium, decorated neurons. Chromium coated fractured nerve processes showed the outer smooth surface of interconnected anastomotic networks or ER tubules, vesicles and cisterns. Cross fractured presynaptic endings of parallel fibers in the molecular layer exhibited spheroidal synaptic vesicles and SE-I edge brightness contrast delineated their limiting plasma membranes. Fractured synaptic endings showed a homogeneous extravesicular material surrounding the synaptic vesicles. The presynaptic dense projections appeared as columnar shaped structures. The postsynaptic membrane and associated postsynaptic density showed a discontinuous surface formed by round subunits 25-35 nm in diameter. The neuroglial cytoplasm ensheathing nerve process exhibited a smooth discontinuous surface. The surface of the myelin sheath showed a mixed population of globular structures 10-30 nm in diameter, apparently corresponding, according to freeze-etch images, to protein and phospholipid microdomains. PMID- 1458440 TI - Increased adhesion of human diabetic platelets to cultured valvular endothelial cells. AB - Diabetes is accompanied by impaired platelet function and accelerated vascular disease. To find out whether a correlation exists between these two complications, and if modifications occurring in diabetic platelets influence their relationship with endothelium, we have studied the interaction between platelets isolated from plasma of diabetic patients and bovine valvular endothelial cells (VEC), in culture. For quantitative analysis, normal and diabetic [3H]-adenine-labeled platelets were incubated with confluent VEC grown in Dulbecco's modified Eagle medium, containing 4.5 g/l glucose, for 30 min at 37 degrees C. After extensive washing and solubilization of the monolayer, the calculated adhesion index showed a two-fold increased adherence of diabetic platelets to VEC as compared to normal platelets. Statistical analysis (by Pitman randomization test) indicated that the adhesion was significantly higher (p = 0.0003) than that of normal platelets to VEC. To partially identify the membrane components implicated in the adhesion process, either platelets or VEC were treated with neuraminidase, trypsin or heparinase prior to the adhesion assay. Trypsin or neuraminidase treatment of platelets significantly diminished their adherence to VEC, suggesting a role of platelets sialylated glycoproteins in the adhesion process. Neuraminidase or heparinase treatment of VEC increased the adhesion of both normal and diabetic platelets, indicating that the cell membrane sialyl residues and heparan sulfate participate in the normal thromboresistant properties of VEC. Transmission and scanning electron microscopy revealed a close apposition between platelets and VEC with the formation of an adhesion plaque, characterized by fine fibrillar bridges between the plasma membranes of the two cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458442 TI - Ultrastructure of Brunner's glands in the horse. AB - Investigation of the duodenal submucosal glands of Brunner in the horse for the first time at the ultrastructural level has clarified some of the unique features of these equine glands. The horse is one of the very few mammals in which Brunner's glands are comprised of both mucous and serous tubuloacinar glands. Although the ultrastructural differences between the serous and mucous cell types are marked, particularly with respect to secretory granules and rough endoplasmic reticula, these cell types closely correspond to serous and mucous cells in the upper digestive system of other mammals. A minor and distinct population of goblet cell-like mucous cells, and endocrine-like cells were also observed in equine Brunner's glands. Both the serous and mucous cells appear to empty into common ducts which enter the base of the duodenal crypts. These submicroscopic cytologic data taken together with other physiologic data would suggest that, in the horse, Brunner's glands function both to provide mucosal protection in the proximal duodenum as well as to release digestive enzymes, such as lipase or other unidentified materials. PMID- 1458443 TI - Genetics and cytogenetics of retinoblastoma. PMID- 1458444 TI - Cytogenetic studies in 112 cases of untreated myelodysplastic syndromes. AB - Cytogenetic studies were performed in 112 untreated cases of myelodysplastic syndrome (MDS) between 1985 and 1990. Among 112 patients who were examined at the time of diagnosis, 54 had an abnormal karyotype (48%). The highest frequency of chromosome abnormalities was observed in refractory anemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-t) and the lowest in refractory anemia with ring sideroblasts (RARS) and chronic myelomonocytic leukemia (CMMoL). Numerical changes were observed in 19 cases and structural in 17; chromosome 8 was most frequently gained (11 cases), whereas chromosome 7 was most frequently lost (6 cases), 5q- in 14 (4 as a sole anomaly); involvement of 7q22 was seen in 3 cases, 11p in 2 patients, 11q in 3 (one patient as a sole anomaly), 12p in 4 (2 patients as a sole anomaly), i(17q) in 4 (3 patients as a sole anomaly), and complex chromosomal defects in 10 patients. If one takes into account the prognosis value, a complex karyotype and the presence of ring chromosomes were correlated with the worst prognosis, followed by -7/7q-; an intermediate prognosis corresponds to i(17q), 12p as a sole anomaly, +8 (as a sole anomaly or plus other anomalies), and involvement of 12p. Patients with a 5q- as a sole anomaly or with a normal karyotype, had the best prognosis. PMID- 1458445 TI - Chromosome 12 in human testicular cancer: dosage changes and their parental origin. AB - Cytogenetically, a marker chromosome interpreted as i(12p) is present in most testicular tumors of germ cell origin. In this study, 22 patients with testicular germ-cell tumors were investigated by Southern blot hybridization to characterize changes in chromosome 12. In comparison with normal DNA, tumor DNA of 18 patients showed increased dosages of 12p accompanied by a comparable or smaller increase or no change in the dosage of centromeric sequences of chromosome 12. A likely interpretation was that most testicular tumors had one or several isochromosomes for 12p that were formed by somatic division of the centromere and that the points of breakage and reunion in the centromeric region were different in different tumors. Allelic 12p fragments showing increased intensity were paternal in four and maternal in three of seven informative cases. Thus, there was no evidence of sex-limited parental imprinting. Furthermore, the observed patterns of allelic fragments suggested that the marker was an i(12p) formed by sister chromatids of one homolog number 12 rather than the result of interchange of genetic material between different homologues. PMID- 1458446 TI - Translocation (12;17)(p11-12;q11-12): a recurrent primary rearrangement in acute leukemia. AB - We identified two patients with acute leukemia in relapse (one lymphoblastic and the other with evidence of mixed lymphoid-myeloid differentiation) with t(12;17)(p12;q11) as the primary karyotypic abnormality. There are six previously reported cases of acute leukemia with an identical or similar translocation. To our knowledge, t(12;17) has not been reported in other forms of neoplasia. A review of these cases suggests that t(12;17) carries a poor prognosis. PMID- 1458447 TI - Variant complex translocation t(8;15;21) in acute myeloblastic leukemia (M2) associated with bilateral chloroma. AB - Complex translocation t(8;15;21)(q22;q21;q22) in a 9-year-old female with acute myeloblastic leukemia (M2) with bilateral chloroma is described. This particular variant type of translocation in M2 type is rare. The importance of variant translocation in defining the critical segment on the chromosomes responsible for phenotypic expression of the disease is emphasized. PMID- 1458448 TI - A t(2;3)(q12-13;p24-25) in follicular thyroid adenomas. AB - We report the cytogenetic analysis of five cases of follicular thyroid adenoma. In two of them, we observed an identical t(2;3)(q12-13;p24-25) as a unique chromosome change. A third case showed a hyperdiploid karyotype with trisomies of chromosomes 7 and 12. Two cases had a normal diploid karyotype. These changes could define subgroups of follicular adenomas endowed with different malignant potential. PMID- 1458449 TI - Cellular proliferation and genetic events involved in the genesis of Burkitt lymphoma (BL) in immune compromised patients. AB - A mathematical model simulating lymphomagenesis based on the two-hit theory of carcinogenesis is presented by contrasting the biologic variables responsible for a high risk of developing Burkitt lymphoma (BL) in three immunosuppressed groups with that of nonendemic BL. In this model, the pro-B lymphocyte is considered to be the target for BL-specific translocations such as t(8;14). With repeated mitosis, the target cell pool expands in the high-risk individual, and, thereby, the opportunities for a spontaneous translocation to arise are increased. The chromosomal translocation endows the target cell with survival advantages, and, hence, lymphoma develops. Modeling results demonstrate that this increased cell proliferation is sufficient in accounting entirely for the increase in tumor prevalence. Preventing enhanced cellular proliferation by obviating immune deficiency and treating patients with agents that restore immunity or have antiviral and antiproliferative properties prior to conversion from polyclonal B cell proliferation to monoclonal malignancy could obviate the development of BL. PMID- 1458450 TI - Prognostic significance of karyotype in a twelve-year follow-up in childhood acute lymphoblastic leukemia. AB - We report a follow-up of 49 children with acute lymphoblastic leukemia (ALL) diagnosed between 1972 and 1978 (follow-up 12-18 years). This series allowed us to analyze the predictive value of karyotype in a long-term follow-up. Karyotypes were abnormal in 33 cases (67.3%): pseudodiploidy in 11 (22.4%), hyperdiploidy > 50 chromosomes in 8 (16.3%), hyperdiploidy 47-50 chromosomes in 11 (22.4%), and hypodiploidy in 3 cases (6.1%). Event-free survival (EFS) and survival studies showed that the outcome of patients was determined only by treatment and karyotype. Eleven patients have survived, nine in first remission (6 years 5 months to 15 years 2 months), and two are in second remission (3 years 8 months and 8 years 2 months). All ploidy groups are represented in these patients. Late relapses can occur in the hyperdiploid > 50 group, thus accounting for shorter EFS than expected, but because of the unusually long second remission of one patient, the rate of surviving patients was higher for this ploidy group than for all other ploidy groups together. Conversely, patients with only numerical abnormalities (no matter which ploidy group they belonged to), had a better outcome than did patients with structural changes or normal karyotypes and no discrepancy between EFS and survival curves was observed in this chromosomal group. Thus, our results suggest that numerical changes only should be considered an indicator of low risk factor, but our results, based on partially banded karyotypes, need to be verified by a current method and therapy. PMID- 1458451 TI - A new nonrandom chromosomal abnormality, t(2;16)(p11.2;p11.2), possibly associated with poor outcome in childhood acute lymphoblastic leukemia. AB - We report a new, nonrandom t(2;16)(p11.2;p11.2) in childhood acute lymphoblastic leukemia (ALL). Three of 292 patients with childhood ALL studied at Indiana University Medical Center had this translocation. All three had additional chromosomal abnormalities at diagnosis and were classified as having low hyperdiploidy (47-49 chromosomes) with structural abnormalities. The patients, two boys and one girl, ranged in age from 3 to 13 years. Peripheral white blood cells (WBC) counts ranged from 1.8 to 107.4 x 10(9)/L, all were classified as French-American-British (FAB) type L1, and all had B-lineage ALL. Because all three patients have relapsed after first remissions of 2 years 8 months to 6 years, the t(2;16) may indicate a poor prognosis and more aggressive treatment may be indicated for such patients. Because this translocation was the sole abnormality in one clone of patient 2 at relapse, it may be considered the primary abnormality. Therefore, it may also be the primary abnormality in the other two patients, and the genes involved in the breakpoints may be important in leukemogenesis. PMID- 1458452 TI - Abnormalities of chromosome 22 in meningiomas and confirmation of the origin of a dicentric 22 by in situ hybridization. AB - We report three cases of meningioma. Case 1 had a dicentric chromosome number 22 resulting in partial monosomy for a portion of the q-arm, i.e., 46,XX,idic(22)(pter-->q11.2::q11.2-->pter) and 46,XX,psu dic(22)(pter- >q11.2::q11.2-->pter), which was the sole clonal abnormality. The origin of the dicentric chromosome from 22 was confirmed by in situ hybridization studies, using biotin-labeled alpha centromeric DNA probes for the acrocentric chromosomes. Case 2 had two distinct clonal abnormalities: deletion of 22q and monosomy of 22. Case 3 also had a deleted 22q. PMID- 1458453 TI - DNA sequence analysis of mutations induced by melphalan in the CHO aprt locus. AB - In previous work, we established that treatment with melphalan (L-phenylalanine mustard) produced a predominance of A.T-->T.A transversions in the Simian virus 40 (SV40)-based shuttle vector pZ189 during replication in human 293 cells. Mutations were induced with varying doses (4-12 microM) melphalan in the aprt gene of the hemizygous Chinese hamster ovary (CHO) cell line D422 to determine whether a similar mutation spectrum would be observed in an endogenous gene. DNA sequence alterations were determined for 39 spontaneous and 41 melphalan-induced independent mutant clones. Other than a predominance of transversions in both systems, the spectrum of melphalan-induced aprt mutations bears little resemblance to the spectrum observed in the supF gene of the shuttle plasmid pZ189. In aprt, mutations at G.C base pairs (bp) predominated (29 of 41 base substitutions). Significantly enhanced mutagenesis was observed at 5' G-G-C 3' and 5' G-G-C-C 3' sites in the aprt gene. Almost half of the melphalan-induced base substitutions occurred at 5' G-N-C 3' sequences, which are believed to be potential interstrand crosslink sites. PMID- 1458454 TI - Acute leukemia with t(1;3)(p36;q21), evolution to t(1;3)(p36;q21), t(14;17)(q32;q21), and loss of red cell A and Le(b) antigens. AB - At transformation of refractory anemia with ring sideroblasts to acute nonlymphocytic leukemia (ANLL) the bone marrow cells of a 75-year-old woman showed three different karyotypes, i.e., 46,XX,46,XX,t(1;3)(p36;q21) and 46,XX,t(1;3)(p36;q21),t(14;17)(q32;q21). She received no antileukemic therapy, and 1 year later, all her bone marrow cells were t(1;3)(p36;q21),t(14;17)(q32;q21). In association with the onset and first 11 months of ANLL, the platelet count increased 10-fold to a peak of 750 x 10(9)/L, providing further evidence that the t(1;3)(p36;q21) translocation causes stimulation of thrombopoiesis. Six months after transformation, her red cells showed reduced expression of A and Leb antigens. Serum alpha-n-3 acetylgalactosaminyl transferase (blood group A transferase) and red cell adenylate kinase were both reduced. The genes for both these substances are at 9q34, which suggests an abnormality here, although cytogenetically chromosome 9 appeared normal. This is the first case with t(1;3)(p36;q21) to show concurrent loss of red cell antigens and the first report detailing the course of untreated ANLL with t(1;3)(p36;q21). PMID- 1458455 TI - Myelodysplastic syndrome and trisomy 14q. AB - Trisomy 14 as a sole karyotypic abnormality in neoplasia is extremely rare. In hematologic disorders, 18 cases have been reported so far, 17 of which involved disorders of the myeloid lineage. Five were cases of myelodysplastic syndrome (MDS), and a further four involved Philadelphia-negative atypical chronic myeloid leukemia. The case presented here is the second case of trisomy 14q in MDS involving the chronic myelomonocytic leukemia subtype. There were certain features in common with some of the previously reported cases. We raise the possibility that this represents a specific entity. PMID- 1458456 TI - Concomitant presence of trisomy 21 and del(9q) in acute myeloid leukemia. AB - We report two cases of acute myeloid leukemia with deletion of the long arm of chromosome 9 [del(9q)] and trisomy 21. del(9q) and +21 do not often occur as a sole karyotypic abnormality in acute myeloid leukemia (AML). Their concomitant presence is rare; the significance of the findings in leukemia is discussed. PMID- 1458457 TI - Cytogenetics of sacral chordoma. AB - Only four cases of chordoma have been described cytogenetically. We report the cytogenetic findings of a fifth case. Chromosome analysis of a primary sacral chordoma from a 69-year-old man showed the following chromosome complement: 43,XY,-2,-3,del(4)(q32),-6,+7,-11,der(12)t(9;12)(q12;p11),add(16)(q23),- 20,add(22)(q13),+mar. PMID- 1458458 TI - Isochromosome 14q and leukemia with dysplastic features. AB - We report a case of chronic myelomonocytic leukemia (CMMoL) with unusual features and an isochromosome 14q as the sole abnormality. A review of the literature suggests that isochromosome 14q (or trisomy 14) is a marker of leukemia with dysplastic features. PMID- 1458459 TI - Trisomy 7 in nonneoplastic kidney tissue cultured with and without epidermal growth factor. PMID- 1458460 TI - Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. AB - Evidence from pathology and epidemiology studies has been provided for a human model of gastric carcinogenesis with the following sequential stages: chronic gastritis; atrophy; intestinal metaplasia; and dysplasia. The initial stages of gastritis and atrophy have been linked to excessive salt intake and infection with Helicobacter pylori. The intermediate stages have been associated with the ingestion of ascorbic acid and nitrate, determinants of intragastric nitrosation. The final stages have been linked with the supply of beta-carotene and with excessive salt intake. Nitrosating agents are candidate carcinogens and could originate in the gastric cavity or in the inflammatory infiltrate. PMID- 1458461 TI - Down-regulation of c-MYC antigen expression in lymphocytes of Emu-c-myc transgenic mice treated with anti-c-myc DNA methylphosphonates. AB - In transgenic mice bearing a murine immunoglobulin enhancer/c-myc fusion transgene (Emu-myc), it was found that antisense DNA methylphosphonates targeted against c-myc mRNA inhibited production of c-MYC protein in peripheral lymphocytes. The decrease in protein was measured 3-4 h after i.v. administration of a 300-nmol dose. c-MYC was detected by immunofluorescence of fixed cells stained with an anti-c-MYC antiserum. In addition, DNA methylphosphonates did not induce acute toxicity following i.v. administration of a 300-nmol dose. An identically administered scrambled sequence oligomer did not decrease c-MYC protein or induce toxicity. Finally, recovery of DNA methylphosphonates from the blood plasma of treated mice indicated that the oligomers remained intact up to 3 h, while their concentrations decreased rapidly for the first h, then slowly decreased over the next 2 h. This is the first demonstration of sequence-specific antisense DNA methylphosphonate inhibition of gene expression in the bloodstream of an animal model. PMID- 1458462 TI - Phase I and pharmacokinetic study of the novel platinum analogue CI-973 on a 5 daily dose schedule. AB - CI-973, a platinum(II) derivative with a 2-methyl-1,4-butanediamine carrier ligand, has activity in cisplatin-resistant tumor models in vitro and in vivo. In a Phase I pharmacokinetic study, 31 patients were treated with CI-973 (24 to 50 mg/m2/day for 5 days; 28-day cycles) given i.v. over 30 min without routine antiemetic prophylaxis or hydration. Of the 29 patients evaluable for maximum tolerated dose determination, most had a performance status of 0 or 1, and most had received prior chemotherapy. Neutropenia was dose limiting at 40 and 50 mg/m2/day. Recovery from neutropenia was generally rapid with nadir counts and recovery usually occurring by Days 15 and 22, respectively. Drug-associated thrombocytopenia was uncommon and never severe, even in patients with Grade 4 neutropenia. Anemia was common, but did not appear dose related. Drug-related nausea and vomiting and changes in renal function were relatively infrequent and mild. No clinically evident ototoxicity was reported, although changes in audiograms were noted in several patients. CI-973 concentrations were measured in plasma ultrafiltrate and urine by high-pressure liquid chromatography. The harmonic mean terminal half-life was 2.0 h. The mean CI-973 renal and nonrenal clearance values were 42.3 and 37.4 ml/min/m2, respectively. The mean recovery of CI-973 in urine was 53% of the administered dose. The mean ratio of CI-973 renal clearance to creatinine clearance was 0.92. Total clearance correlated with creatinine clearance (r2 = 0.63). A relationship between toxicity, expressed as the percentage of reduction in absolute granulocyte count, and area under the CI 973 plasma concentration-time curve was found in a subgroup of "good-risk" patients. This relationship, described well by a sigmoidal Emax pharmacodynamic model, did not hold for patients with extensive prior therapy or poor performance status. A model for toxicity prediction based on dose and creatinine clearance has been derived and will be validated in future studies. The recommended Phase II dose of CI-973 is 30 mg/m2/day for 5 days. PMID- 1458463 TI - Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. AB - Human-mouse chimeric immunoglobulins G1 and G3 (IgG1 and IgG3) (ChG1, ChG3) and "complementarity-determining region"-grafted, humanized IgG1 and IgG3 (HuG1, HuG3) constructs of the mouse monoclonal antibody (mAb) M195 were characterized. M195 is a murine immunoglobulin G2a (IgG2a), anti-CD33 mAb, specifically reactive with acute myelogenous leukemia cells, that is active as an antileukemia agent in humans. The new mAb constructs maintained specificity and biological function, including rapid internalization after binding to the cell surface, which has been important for delivery of therapeutic isotopes in patients. Although previously reported complementarity-determining region-grafted mAbs had reduced avidities, the HuG1 and HuG3 M195 showed up to an 8.6- and 4-fold higher binding avidity, respectively, than the original murine mAb. All constructs were effective at mediating rabbit complement-mediated cytotoxicity against HL60 targets. Fibroblasts transfected with CD33 genes and expressing high levels of CD33 antigen were also lysed in the presence of human complement, but HL60 cells or fibroblasts with lower CD33 levels were not killed. Thus, the inability of M195 and constructs to kill HL60 targets with human complement is due to the much lower antigen density on HL60 cells compared to CD33+ fibroblasts. Unlike the murine M195, the chimeric and humanized M195 demonstrated antibody-dependent cell mediated cytotoxicity using human peripheral blood mononuclear cells as effectors. Because the chimeric and humanized M195 have improved avidities as compared to the original M195 and have, in addition, the potential to avoid human anti-mouse antibody responses and to recruit human effector functions, these new constructs may be useful therapeutically, either alone or conjugated to toxins or isotopes, in the treatment of acute myelogenous leukemia. PMID- 1458464 TI - High molecular weight transforming growth factor beta is excreted in the urine in active nodular sclerosing Hodgkin's disease. AB - To measure the in vivo secretion of high molecular weight (HMW) transforming growth factor (TGF)beta by Reed-Sternberg cells from patients with nodular sclerosing Hodgkin's disease, we studied the urine samples from untreated patients. The urinary proteins did not promote the proliferation of NIH-3T3 cells in monolayer culture and contained similar amounts of total TGF activity when compared with normal controls. Urinary proteins from 24 different control and test urines were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Either of two primary antibodies were used for immunoblot detection: (a) affinity column purified polyclonal anti-TGF beta 1 prepared against platelet TGF beta 1 or (b) monoclonal anti-HMW-TGF beta prepared against HMW-TGF beta secreted by cloned L-428 Reed-Sternberg cells. All patients with active nodular sclerosing Hodgkin's disease had a detectable HMW-TGF beta (approximately 300,000) which cross-reacted with both anti-TGF beta 1 and anti HMW-TGF beta. Purification demonstrated HMW-TGF beta which was active at physiological pH. Twelve control urine samples from healthy adults and 5 follow up samples from the Hodgkin's patients after successful treatment contained no detectable urinary HMW-TGF beta. The in vivo production of HMW-TGF beta in untreated nodular sclerosing Hodgkin's disease supports the conclusion that this growth factor is secreted in large amounts by Reed-Sternberg cells or cells stimulated by Reed-Sternberg cells. PMID- 1458465 TI - Pharmacokinetics and therapeutics of sterically stabilized liposomes in mice bearing C-26 colon carcinoma. AB - Three different liposome types were compared for blood clearance and tissue uptake in mice bearing C-26 colon carcinoma growing either s.c. or in liver. Therapeutic experiments were performed with the liposome preparation showing the highest tumor uptake. Liposomes were composed of solid-phase phosphatidylcholine, either distearoyl phosphatidylcholine or hydrogenated soy phosphatidylcholine, and cholesterol at a 2:1 molar ratio. These liposomes were compared with similar but sterically stabilized liposomes (SL) which, in addition, contained either GM1 ganglioside or phosphatidylethanolamine derivatized with poly(ethylene glycol). Pharmacokinetic analysis of drug disposition was based on the areas under the curve for liposome-entrapped 67Ga uptake per gram of tissue up to 96 h following i.v. injection. The highest tissue area under the curve values with both liposome types were obtained in spleen, liver, and tumor. However, the sterically stabilized liposomes gave an area under the curve value 2-3-fold higher in the s.c. tumor and about 2-fold lower in liver and spleen. The therapeutic efficacy of doxorubicin (DOX) and epirubicin (EPI) encapsulated in poly(ethylene glycol) derivatized phosphatidylethanolamine-containing liposomes was compared with that of free drug at two doses, 6 and 9 (or 10) mg/kg animal weight. Liposomes containing drug were injected either as a single dose, at different times following tumor implantation, or as three weekly doses starting 10 days after implantation. When injected as a single dose, liposome-encapsulated DOX had the maximal effect on tumor growth when injected 6 to 9 days after tumor implantation. When injected as three weekly doses, with treatment starting with a delay of 10 days, tumors which had grown to a size of approximately 0.05-0.1 cm3 regressed in groups of animals treated with either liposome-encapsulated drug (SL DOX or SL-EPI) but continued to grow unabated in untreated mice and in mice receiving either of the free drugs. Survival of tumor-bearing animals treated with either SL-EPI or SL-DOX was significantly prolonged. Animals receiving saline, EPI, or DOX survived a mean of 50, 62, and 49 days, respectively, following tumor implantation. Eight of nine and nine of 10 animals receiving 6 and 9 mg/kg SL-EPI, respectively, survived to 120 days. Ten of 10 animals in both groups receiving 6 and 9 mg/kg SL-DOX survived to 120 days. None of the surviving animals in the SL-EPI and SL-DOX group showed any histological evidence of tumor at the conclusion of the experiment (120 days).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1458466 TI - alpha-Difluoromethylornithine alters calcium signaling in platelet-derived growth factor-stimulated A172 brain tumor cells in culture. AB - alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of the polyamine biosynthetic enzyme ornithine decarboxylase, inhibits the growth of brain tumor cell lines and is undergoing clinical trials as a treatment for brain tumors. Platelet-derived growth factor (PDGF) is thought to regulate the growth and development of precursors of both normal and neoplastic astrocytic cells; calcium signaling is thought to play a role in the transduction of PDGF signals. Using laser fluorescence image cytometry, flow cytometry, and spectrofluorometry, we studied the effect of DFMO on the calcium signals induced by PDGF in A172 human glioblastoma cells. Four days of treatment with 5 mM DFMO substantially shortened PDGF-induced calcium signals. The effect was reversed more than 10 h but less than 24 h after putrescine treatment, even though polyamines were repleted 4 h after putrescine and spermidine were added. DFMO did not substantially affect intracellular calcium release or the timing of the opening and closing of plasma membrane calcium channels. These findings support the notion that calcium signaling may be a target for inhibitors of polyamine metabolism. PMID- 1458467 TI - Modulation of cisplatin resistance in human malignant melanoma cells. AB - Previous studies have shown that the combination of dacarbazine, carmustine, cisplatin (DDP), and tamoxifen (TAM) produced a 53% overall response rate in patients with disseminated melanoma. Deletion of TAM from the regimen resulted in a fall in the response rate to 10%, and reincorporation of TAM returned the response rate to 52%, suggesting an important role for TAM. Using the human melanoma cell line T-289, we examined the nature of the interaction between TAM and each member of this combination in clonogenic assays in soft agar. The combination of TAM with DDP was highly synergistic as demonstrated by median effect analysis, whereas TAM was antagonistic with carmustine and an activated form of dacarbazine. The mean combination index at 50% kill was 0.26 +/- 0.02 (mean +/- SD) for TAM and DDP. This marked synergism was observed at concentrations of TAM that are clinically achievable. TAM had no effect on the uptake of the DDP analogue [3H]dichloro(ethylenediamine)platinum(II). There was no effect on the formation or repair of DDP intrastrand DNA adducts. Similarly, there was no effect demonstrated on the intracellular concentrations of glutathione or metallothioneins. We conclude that the interaction between TAM and DDP is truly synergistic in this cell line and is accomplished through none of the four mechanisms commonly associated with DDP resistance. PMID- 1458468 TI - Resistance of murine lung tumors to xenobiotic-induced cytotoxicity. AB - Studies were performed to test the hypothesis that urethane-induced murine lung tumors exhibit xenobiotic resistance and alterations in pulmonary cytochrome P 450 enzymes. 1,1-Dichloroethylene, naphthalene, and paraquat were administered to tumor-bearing and control mice to elicit acute lung cytotoxicity, and responses were evaluated in tumors (papillary and solid), uninvolved surrounding tissue, and untreated control lung. 1,1-Dichloroethylene (125 mg/kg, i.p.) and naphthalene (225 mg/kg, i.p.) caused preferential necrosis of Clara cells in control lungs and uninvolved tissue of tumor-bearing lungs. In contrast, papillary and solid tumors were both resistant to 1,1-dichloroethylene-induced cytotoxicity. Paraquat (10, 20 mg/kg, i.v.) elicited Clara cell damage in control lungs and uninvolved lung tissue of tumor-bearing mice, with minor disruption of the alveolar epithelium. Neither papillary nor solid tumors sustained any apparent cell damage from paraquat. Immunoblots of P-450 enzymes confirmed constitutive expression of CYP2B1 in control lung and uninvolved lung tissue of tumor-bearing mice, but this P-450 enzyme was not detected in either adenomas or carcinomas. Lung CYP1A1 was inducible by beta-naphthoflavone in non-tumor-bearing mice and uninvolved tissue of tumor-bearing mice; however, inducibility was decreased in adenomas and abolished in carcinomas. These results demonstrate resistance of lung tumor cells to chemically induced cytotoxicity and diminished expression of cytochrome P-450 enzymes in tumors. PMID- 1458469 TI - Clonal growth of hepatitis B virus-integrated hepatocytes in cirrhotic liver nodules. AB - A total of 83 cirrhotic nodules (pseudolobules) individually collected from 11 cirrhotic livers of hepatitis B virus carrier patient were analyzed for the frequency and mode of hepatitis B virus integration as well as histological features. Southern blot analysis disclosed discrete bands at higher molecular weight region in 26 of 83 nodules (31.3%), indicating a clonal growth of hepatocytes with viral integration. Considerable variation (0-75%) existed in the positive rates for discrete bands in nodules among livers. Molecular cloning revealed the sequence flanking an integrated viral sequence to be host DNA and thus confirmed true integration. Histological analysis, however, did not reveal any neoplastic-appearing foci of growth within nodules, despite the fact that the detection sensitivity would predict clones of more than 10(5) cells to give rise to clonal integration patterns on Southern blot analysis. The question of whether clonal expansion of hepatocytes reflects any viral integration-associated growth advantage and/or a preneoplastic condition awaits future studies. PMID- 1458470 TI - Lower heat shock factor activation and binding and faster rate of HSP-70A messenger RNA turnover in heat sensitive human leukemias. AB - Normal bone marrow progenitors and some leukemic cells develop only a limited amount of thermotolerance. Further, once developed, thermotolerance decays at a faster rate than that normally observed in cells of nonhemopoietic origin. Thermotolerance induction and maintenance correlates with reduced levels of expression of various M(r) 70,000 heat shock proteins (HSP-70) mRNAs after heat shock. We have now compared the accumulation of HSP-70 proteins in heat-shocked human leukemic cells KG-1, HL-60, and K562 to that in Ht1080, a colon carcinoma cell line. We have found reduced accumulation of HSP-70 proteins in all leukemic cells. The rate of decay of HSP-70A mRNA, measured following heat shock by using actinomycin D treatment to inhibit further RNA synthesis, was more rapid in KG-1 and HL-60 cells compared to Ht1080 cells. The half-life of HSP-70A mRNA was 2 h in KG-1 and HL-60 cells while in Ht1080 cells it was > 7 h. HSP-70A mRNA is known to decay with a half-life of 2 h in unheated cells; this is increased to > 7 h following heat shock. We therefore postulate that leukemic cells lack the mechanism to stabilize HSP-70A mRNA after heat shock. One postulated mechanism for HSP-70 mRNA decay rate is known to be due to the nucleotide sequences at the 3'-untranslated region. We examined the 3'-untranslated region in leukemic cells. No sequence variations, however, were observed at either the genomic or the complementary DNA levels between leukemic or nonleukemic tumor cells. Heat shock factor activation and binding by gel retardation assays showed that KG-1 and HL 60 cells had a reduced heat shock factor binding to the heat shock element when compared to K562 and Ht1080 cells. Furthermore, HSF-1 mRNA was found to be expressed at relatively lower levels in HL-60 cells when compared to Ht1080 or KG 1 cells. In conclusion, reduced HSP synthesis and accumulation of leukemic cells after heat shock correlates with the reduction in heat shock factor-heat shock element binding and a faster HSP-70A mRNA decay rate that is observed in these cells. PMID- 1458471 TI - Effects of ketoconazole on the proliferation and cell cycle of human cancer cell lines. AB - The growth-inhibitory effects of ketoconazole, an antifungal agent which inhibits arachidonic acid lipoxygenases and cytochrome P-450 enzymes, were tested in human colon and breast cancer cell lines. In the serum independent HT29-S-B6 colon cell clone, ketoconazole reduced cell proliferation and [3H]thymidine incorporation in a dose-dependent fashion, with a 50% inhibitory concentration of approximately 2.5 microM. Flow cytometry showed an accumulation of cells in the G0-G1 phase of the cell cycle and a concomitant decrease of the percentage of cells in S phase. Ketoconazole also inhibited [3H]thymidine incorporation in the hormone independent breast cancer cells MDA-MB-231 and Evsa-T, with respective 50% inhibitory concentration of approximately 13 and 2 microM. The mechanism of action of ketoconazole is unknown. However, another lipoxygenase inhibitor, BW755C, inhibited only weakly [3H]-thymidine incorporation and accumulated the cells in S and G2. Conversely, clotrimazole and SKF525A, inhibitors of cytochrome P-450 enzymes, had effects similar to those of ketoconazole on HT29-S-B6 cells whereas metronidazole and secnidazole, other azole derivatives which do not inhibit cytochrome P-450 enzymes, had no effect. The results suggest that cytochrome P-450 enzyme(s) activity(ies) could be implicated in the antiproliferative effects of ketoconazole. PMID- 1458472 TI - Isolation and characterization of a highly malignant variant of the SW480 human colon cancer cell line. AB - We found that the human colon cancer cell line SW480 consists of two distinct subpopulations which we have designated E-type (epithelial) and R-type (round). Pure cultures of each type were obtained by subcloning, and both have maintained their characteristic phenotypes for at least 1 year (40 passages). E-type cells are the major (> 98%) type in the parental SW480 cell line. They form flat epithelial-like colonies. In contrast, R-type cells, which constitute a minor fraction (< 2%) of the parental cell line, have a rounded shape and grow in clusters of piled-up cells. Compared to E-type cells or the parental SW480 cells, isolated R-type cells display decreased doubling time, loss of contact inhibition, less adhesiveness to culture plates, higher anchorage-independent growth in soft agar, and a much more aneuploid karyotype. When injected s.c. into nude mice, R-type cells produce much larger tumors within the same period of time than E-type cells, and the tumors are less differentiated than those produced by the E-type cells. Cell fusion experiments between R-type and E-type cells revealed that the R-type phenotype is dominant, and the results suggest that this is due to one or a few genetic changes. Taken together, these findings suggest that the R-type cells represent a more malignant variant of the E-type cells. They may be useful, therefore, for studying mechanisms involved in tumor progression. PMID- 1458473 TI - Overexpression of metallothionein in Chinese hamster ovary cells and its effect on nitrogen mustard-induced cytotoxicity: role of gene-specific damage and repair. AB - Overexpression of metallothionein in mammalian cells has been associated with protection from cytotoxic chemicals and acquired resistance of tumors to cytotoxic drugs. The mechanism of this effect, however, remains unclear. We have explored whether cytotoxicity of the bifunctional alkylating agent nitrogen mustard was correlated with the extent of DNA damage formation and repair in the metallothionein gene regions in Chinese hamster ovary cells. The DNA damage and repair were examined in metallothionein-overexpressing, cadmium-resistant Chinese hamster ovary cells, Cdr200T1, with or without zinc-induced transcriptional activation, and in the parental CHO-met- cell line. The zinc-induced Cdr200T1 cells tolerated significantly higher doses of nitrogen mustard than did the uninduced Cdr200T1 variant. The parental CHO-met- cells, which did not have any detectable metallothionein expression, were even more resistant to nitrogen mustard than the zinc-induced Cdr variants. Nitrogen mustard-induced N alkylpurines were formed with a higher frequency in inactive genomic regions than in the active genes. The removal of N-alkylpurines was similar in the active MT I gene region in Cdr200T1 and the silent MT I gene region in the parental cells, and the expression of these genes was determined by Northern assay. The MT II gene-containing region was repaired less efficiently than the MT I gene, independently of zinc induction. Further, preferential repair of nitrogen mustard induced N-alkylpurines were detected in a single copy of the essential active dihydrofolate reductase gene as compared to a downstream noncoding region. This preferential repair was unaffected by the presence of zinc. Neither damage formation nor repair kinetics in the MT gene regions seemed to parallel the observed spectrum of sensitivity to HN2. PMID- 1458474 TI - Identification of a protein factor secreted by 3T3-L1 preadipocytes inhibitory for the human MCF-7 breast cancer cell line. AB - The 3T3-L1 cell line is a preadipocyte cell line derived from the Swiss 3T3 mouse fibroblast cell line. We have compared the effect of 3T3-L1 conditioned medium (3T3-L1 CM) and Swiss 3T3 conditioned medium (3T3 CM) on the growth of normal mouse mammary cells (NMMG) and the human MCF-7 breast carcinoma cell line. 3T3 CM increased the growth of both NMMG and MCF-7 cells by 19 +/- 2% (SD) and 24 +/- 3%, respectively, and increased thymidine incorporation by 74 +/- 4% and 104 +/- 8%, respectively. Conditioned medium from 3T3-L1 cells stimulated the growth of NMMG cells by 64 +/- 2%; in contrast, 3T3-L1 CM inhibited the growth of MCF-7 cells by 36 +/- 1%. In parallel with these growth studies, thymidine incorporation increased by 20 +/- 4% in NMMG cells and decreased by 72 +/- 5% in the MCF-7 cells. Moreover, a similar effect was also noted in NCI H630 colon cancer cells, where 3T3-L1 CM produced a 58 +/- 4% decrease in growth and a 82 +/ 6% decrease in thymidine incorporation. Heating the 3T3-L1 CM at 100 degrees C for 30 min destroyed all inhibitory activity. Several known inhibitory growth factors (fibroblast growth factor, 20 ng/ml; interleukin 6, 1000 units/ml; tumor necrosis factor alpha, 15 ng/ml; transforming growth factor beta, 1 ng/ml) were tested for activity in the MCF-7 cells. Tumor necrosis factor alpha and transforming growth factor beta produced a 97% and 67% inhibition of thymidine uptake, respectively, whereas interleukin 6 and fibroblast growth factor had no effect. Neither transforming growth factor beta nor tumor necrosis factor alpha activity was detectable in 3T3-L1 CM using an enzyme-linked immunosorbent assay. High-performance liquid chromatography fractionation of the 3T3-L1 CM revealed that the inhibitory activity eluted at a molecular weight of 67,000; moreover, silver staining of these eluates on a denaturing polyacrylamide gel revealed that M(r) 69,000 peptide was the predominant protein band in the inhibitory fractions. Thus 3T3-L1 CM stimulates the growth of normal breast epithelial cells and inhibits the growth of MCF-7 breast cancer cells. This inhibitory activity appears to be due to a protein secreted by 3T3-L1 preadipocytes. PMID- 1458475 TI - Inability of leucovorin to rescue a naturally methotrexate-resistant human soft tissue sarcoma cell line from trimetrexate cytotoxicity. AB - A human lymphoblastoid line (RPMI-1788), a methotrexate-sensitive human fibrosarcoma cell line (HT-1080), and a naturally resistant mixed mesodermal human sarcoma cell line with impaired methotrexate polyglutamylation (HS-42), recently established in our laboratory, were used to compare the ability of leucovorin to prevent trimetrexate cytotoxicity. Growth inhibition and an in situ thymidylate synthesis activity assay showed that inhibitory effects of trimetrexate (1 to 10 microM), 24-h exposure, were prevented by 10 microM leucovorin in the RPMI-1788 and HT-1080 cell lines but not in the HS-42 cell line. Total intracellular reduced folates increased about 2-fold in the three cell lines after exposure to leucovorin (10 microM) for 4 h, and after a 6-hour efflux remained elevated (1.5- and 1.3-fold of control levels) in RPMI-1788 and HT-1080 cells but decreased to 80% of control levels in HS-42 cells. Although uptake of leucovorin and levels of N5,N10-methylenetetrahydrofolate achieved after leucovorin administration were similar in RP-MI-1788 and HS-42 cells, polyglutamylate forms of this coenzyme were less in the HS-42 cells as compared to RPMI-1788 cells. Based on these studies, the combination of trimetrexate with leucovorin should be further investigated as a way to increase the therapeutic index in some patients with soft tissue sarcomas. PMID- 1458476 TI - Regulation of smooth muscle alpha-actin promoter in ras-transformed cells: usefulness for setting up reporter gene-based assay system for drug screening. AB - Oncogenic activation of ras results in changes in the transcription of several genes leading to uncontrolled cell growth. In this paper, we demonstrate that transformation of fibroblast cells by the ras oncogene leads to transcriptional repression of the smooth muscle alpha-actin promoter. Transient transfection analysis of plasmids containing the 5' upstream region of the human alpha-actin gene fused to human growth hormone or bacterial chloramphenicol acetyltransferase coding sequences into Rat-2 and ras-transformed Rat-2 (HO6) cells indicates that alpha-actin promoter is repressed in ras-transformed cells. In addition, stable rat fibroblast cell lines expressing human growth hormone or beta-galactosidase under the control of alpha-actin promoter exhibit repressed reporter gene activity following transformation by the ras oncogene. alpha-Actin promoter driven beta-galactosidase activity is derepressed in revertants of ras transformed stable cell lines. This revertant cell line expresses elevated levels of ras p21 protein and is resistant to retransformation by Ki and Ha-ras oncogenes. The revertant may have either a defective target protein whose activity is essential for the transforming activity of ras or an activated tumor suppressor gene which can suppress the activity of ras. These results indicate that smooth muscle alpha-actin promoter activity is a sensitive marker to follow phenotypic changes following transformation by ras and subsequent reversion. The advantages of this alpha-actin promoter-reporter gene assay system to screen for drugs that inhibit the transforming activity of ras, either directly or indirectly, are discussed. PMID- 1458477 TI - Relationship of cellular glutathione to the cytotoxicity and resistance of seven platinum compounds. AB - The role of glutathione (GSH) in the effectiveness of and resistance to 7 platinum compounds [5 Pt(II) and 2 Pt(IV) drugs] was evaluated in a 8.6-fold cisplatin (CDDP)-resistant human small cell lung cancer cell line (GLC4/CDDP), the parent GLC4 line, a 3.7-fold CDDP-resistant human embryonal carcinoma cell line (Tera-CP), and the parent Tera line (NTera2/D1). Resistance factors for both CDDP-resistant cell lines were determined after continuous incubation (4 days) with CDDP. Continuous incubation with the other studied platinum drugs revealed complete cross-resistance for carboplatin (CBDCA) and zeniplatin but less for enloplatin (ENLO) and iproplatin in both models. Tetraplatin and lobaplatin showed, respectively, partial and complete cross-resistance in GLC4/CDDP but no cross-resistance in Tera-CP. GSH level, but not glutathione S-transferase activity, of the 4 cell lines correlated with platinum drug concentrations inhibiting cell survival by 50% after continuous incubation (r = 0.86, P < 0.05). GSH depletion by DL-buthionine-S,R-sulfoximine (BSO) increased sensitivity, as measured after a 4-h exposure to the drugs, of GLC4/CDDP for CDDP 2.0-fold, for CBDCA 1.7-fold, for zeniplatin 1.7-fold, and almost to the level of the sensitive GLC4 for ENLO, whereas no effect was observed for lobaplatin and the Pt(IV) compounds iproplatin and tetraplatin. BSO-modulating effect was higher in the sensitive GLC4 line for most compounds; therefore reduction of resistance could be achieved only for CDDP and ENLO. In contrast to GLC4, no modulation occurred in Tera. In Tera-CP BSO increased sensitivity for CDDP 1.5-fold, for CBDCA 1.9 fold, and for zeniplatin 1.2-fold; no effect was observed for ENLO, lobaplatin, and the Pt(IV) compounds. Reduction of CDDP resistance by BSO was known to occur with identical cellular platinum levels and higher Pt-DNA binding in GLC4/CDDP. However, pretreatment with BSO followed by 4 h ENLO incubation increased cellular platinum levels in both GLC4 and GLC4/CDDP while Pt-DNA binding remained unchanged. In conclusion, GSH reflected sensitivity to platinum-containing drugs. However, since the involvement of GSH differed between the models and the various platinum drugs, the effect of modulation with BSO was unpredictable. PMID- 1458478 TI - Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in 7,12 dimethylbenz[a]anthracene-initiated SENCAR mouse skin by a polyphenolic fraction isolated from green tea. AB - Our laboratory has been studying cancer chemopreventive effects of polyphenolic fraction isolated from green tea (GTP). In prior studies we have shown that (a) GTP possesses antigenotoxic effects in various test systems; (b) topical application of GTP protects against UV radiation and chemical carcinogen-induced tumorigenesis in murine skin; and (c) feeding of GTP in drinking water p.o. to mice protects against carcinogen-induced forestomach and lung tumorigenesis. Recently, we showed that in a dose-dependent manner GTP inhibits tumor promoter caused induction of epidermal ornithine decarboxylase activity in SENCAR mice (R. Agarwal et al., Cancer Res., 52: 3582-3588, 1992). In the present study, we assessed the effect of GTP on TPA-induced skin tumor promotion in 7,12 dimethylbenz(a)anthracene-initiated SENCAR mouse. Topical application of varying doses of GTP (1-24 mg) 30 min prior to that of each TPA application resulted in highly significant protection against skin tumor promotion in a dose-dependent manner. The animals pretreated with GTP showed substantially lower tumor body burden such as decrease in total number of tumors per group, number of tumors per animal, tumor volume per mouse, and average volume per tumor, as compared to the animals that did not receive GTP. Since TPA-induced epidermal cyclooxygenase and lipoxygenase activities and edema and hyperplasia are conventionally used markers of skin tumor promotion, we also assessed the effect of preapplication of GTP on these parameters. As quantitated by the formation of prostaglandin and hydroxy eicosatetraenoic acid metabolites from, respectively, cyclooxygenase- and lipoxygenase-catalyzed metabolism of arachidonic acid, skin application of GTP to SENCAR mice resulted in significant inhibition of TPA-caused effects on these 2 enzymes. Prior application of GTP to mouse skin also resulted in 30-46% inhibition of TPA-induced epidermal edema and hyperplasia. The results of the present study suggest that GTP possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter induced epidermal ornithine decarboxylase, cyclooxygenase and lipoxygenase activities, edema, and hyperplasia. Further studies are in progress to define which component present in GTP is responsible for its anti-skin tumor-promoting effects. PMID- 1458479 TI - Novel expression of gastrin (cholecystokinin-B) receptors in azaserine-induced rat pancreatic carcinoma: receptor determination and characterization. AB - Many reports have emphasized the role of gastrin as a growth factor for normal gastrointestinal mucosa and gastrointestinal cancers. Recent studies have pointed out that this peptide acts also as a growth factor for the pancreatic cancer cell line AR42J. This effect is mediated by gastrin [cholecystokinin (CCK)-B] receptors. In the present study, we investigated gastrin (CCK-B) receptor expression in the azaserine-induced rat pancreatic carcinoma DSL-6, comparing it to normal rat pancreas, and we also characterized CCK receptor subtypes in this tumor. The results showed that there is extensive gastrin binding to the DSL-6 pancreatic carcinoma. No evidence of specific gastrin binding to normal pancreas was found. Analysis of the ability of gastrin-17-I to inhibit 125I-gastrin-I binding demonstrated that gastrin bound to a single class of receptors with a Kd of 0.21 +/- 0.04 nM and a binding capacity of 184 +/- 29 fmol/mg protein. 125I Gastrin-I binding was inhibited by the specific CCK-B receptor antagonist L365,260 approximately 40 times more effectively than by the specific CCK-A receptor antagonist L364,718. Analysis of the ability of cholecystokinin octapeptide (CCK-8) to inhibit 125I-Bolton-Hunter-CCK-8 binding revealed two CCK binding sites, i.e., a high affinity site and a low affinity site. The observed binding affinities of CCK-8 were then introduced into the computer analysis of the dose-inhibition curve of the ability of gastrin-17-I to inhibit binding of 125I-Bolton-Hunter-CCK-8, which was significantly better fit by a three-site model than by a two-site model. The three sites meet the criteria for CCK-B, high affinity CCK-A, and low affinity CCK-A receptors. The binding capacity of CCK-B receptors constitutes 34% of the total high affinity CCK binding sites. This study demonstrated that DSL-6 pancreatic carcinoma expresses three subtypes of CCK receptors. Gastrin (CCK-B) receptors, which were not detected in normal rat pancreas, constitute about one third of the total high affinity CCK receptors. We suggest that novel expression of gastrin (CCK-B) receptors may be generated by gene mutation or amplification during carcinogenesis and may play an important role in promoting tumor growth. PMID- 1458480 TI - Immunogenicity and safety of a recombinant vaccinia virus vaccine expressing the carcinoembryonic antigen gene in a nonhuman primate. AB - We have previously reported the development of a recombinant vaccinia virus vaccine expressing the human carcinoembryonic antigen (CEA) gene, designated rV(NYC)-CEA. This construct has been shown to elicit specific anti-CEA immune responses and an antitumor effect in a murine tumor model. In the studies reported here, the safety and immunogenicity of this recombinant vaccinia virus were evaluated in a rhesus monkey model. Human CEA is a M(r) 180,000 glycoprotein expressed in approximately 90% of gastrointestinal carcinomas and in some breast and non-small cell lung carcinomas. This family also includes normal cross reacting antigen (NCA). Rhesus monkeys, like humans, have some NCA on the surface of their granulocytes. Eight monkeys were immunized 3 or 4 times by skin scarification with the recombinant CEA vaccine and four monkeys received wild type vaccinia virus as control. After three vaccinations, all rV(NYC)-CEA vaccinated animals exhibited a strong anti-CEA antibody response as measured by enzyme-linked immunosorbent assay. The functional ability of these antibodies to mediate lysis of a CEA-bearing tumor cell was demonstrated using human effector cells. This response could be enhanced by interleukin 2. Cellular immunity to CEA was measured by delayed-type hypersensitivity upon intradermal challenge with purified CEA. Only those animals receiving the recombinant vaccine displayed significant anti-CEA responses. Furthermore, peripheral blood mononuclear cells from immunized monkeys were found to proliferate in response to CEA stimulation. All vaccinated monkeys developed local skin irritation at the site of the vaccination, regional lymphadenopathy, and low-grade fevers after immunization. Following immunization with rV(NYC)-CEA, the response was consistent with the usual constitutional symptoms seen with human smallpox virus immunization. Blood counts, differentials, and hepatic and renal chemistries remained normal in all animals throughout the study and for up to 1 year following the primary vaccination. No evidence of immunological cross-reactivity to NCA was found by either a fall in the granulocyte count or analyses for anti-NCA antibodies. Thus, the rV(NYC)-CEA vaccine appears to be safe in rhesus monkeys. The administration of a CEA recombinant vaccine to rhesus monkeys induces both a humoral and a cell mediated immune response directed against human CEA. PMID- 1458481 TI - Potent and specific inhibition of p60v-src protein kinase both in vivo and in vitro by radicicol. AB - A fungal metabolite, radicicol, with a macrocyclic ring induced the reversal of transformed phenotypes of v-src-transformed fibroblasts (Rous sarcoma virus transformed 3Y1 rat fibroblast) at a quite low concentration of 0.1 microgram/ml. Actin stress fibers reappeared in the transformed cells after treatment with radicicol. Radicicol reduced the intracellular level of autophosphorylation of p60v-src as well as the level of other tyrosine-phosphorylated proteins in a dose dependent manner. In vitro kinase assay revealed that radicicol effectively inhibited not only autophosphorylation but also transphosphorylation activities of purified p60v-src with a concentration producing 50% inhibition of 0.1 microgram/ml. However, radicicol showed no inhibitory effect on protein kinase C or protein kinase A. These results suggest that radicicol is a novel and specific protein-tyrosine kinase inhibitor and that the decreased level of tyrosine kinase activity of p60v-src causes reversion of transformed phenotypes of Rous sarcoma virus-transformed 3Y1 rat fibroblast. Furthermore, differentiation of Friend leukemia cells, which is one of the known characteristic phenomena associated with the inhibition of tyrosine kinase, was also induced in the concentration range of 0.05-0.5 microgram/ml, suggesting that the agent is useful for the analysis of differentiation as well as the kinase-mediated signal transduction. PMID- 1458482 TI - Carcinogenicity studies of fluoxetine hydrochloride in rats and mice. AB - The antidepressant drug fluoxetine HCl was tested for carcinogenicity in three well designed and controlled studies in Fischer rats and C57BL/6 x C3H F1 mice. The compound was administered to the animals for 24 months at dietary doses of approximately 0, 0.5, 2.0, or 10.0 mg/kg body weight in rats and 1.0, 5.0, or 10.0 mg/kg in mice. The highest dose tested was a maximum tolerated dose for both species as evidenced by clinical signs (rats and mice) and some mortality (mice) referable to central nervous system pharmacological effects, decreased weight gain (rats), and histopathological changes of phospholipidosis (rats) and hepatic fatty change (mice). There was no evidence of an increased incidence of any type of unusual or commonly occurring spontaneous neoplasm in either rats or mice. There were statistically significant decreases in a few commonly occurring neoplasms. The data reported herein provide convincing evidence that fluoxetine is neither a complete carcinogen nor a tumor promoter. PMID- 1458483 TI - Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. AB - The significance of apoptosis in relation to the development and progression of prostate cancer remains largely undefined. bcl-2 is an oncogene that functions by overriding apoptosis. bcl-2 expression was localized to the basal epithelial cells in the normal human prostate with the use of immunohistochemistry. Androgen dependent and androgen-independent prostate carcinomas were evaluated immunohistochemically for bcl-2 expression. bcl-2 was undetectable in 13 of 19 cases of androgen-dependent cancers. In contrast, androgen-independent cancers displayed diffuse, high levels of bcl-2 staining (P < 0.01). In rats, steady state levels of bcl-2 mRNA, assessed by S1 assays, reached maximum levels 10 days following castration. Addition of exogenous testosterone with, or without, flutamide demonstrated that the increased bcl-2 mRNA resulted from androgen ablation. Our findings indicate that bcl-2 expression is augmented following androgen ablation and is correlated with the progression of prostate cancer from androgen dependence to androgen independence. PMID- 1458484 TI - Consistent disruption of the AML1 gene occurs within a single intron in the t(8;21) chromosomal translocation. AB - The AML1 gene on chromosome 21 was rearranged by the t(8;21) chromosomal translocation in acute myeloid leukemia (AML). Southern blot analysis of 21 AML patients with t(8;21), including three with complex translocations, t(8;V;21), demonstrated that all the breakpoints occurred at random within a single intron between two coding exons of AML1. Clustering of the breakpoints in the restricted intron suggests the formation of a unique fusion gene between the AML1 gene and a presumable counterpart gene on chromosome 8. Nucleotide sequencing of the breakpoint region revealed that the translocation event was accompanied by deletion of a short stretch of nucleotides. PMID- 1458485 TI - Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. AB - The transforming growth factor beta s (TGF-beta) comprise a family of M(r) 25,000 pluripotent growth factors which have been implicated in the development and progression of human breast cancer. Conflicting data suggest that TGF-beta has the potential to either inhibit or promote the progression of mammary neoplasia. We therefore examined a pathological library of malignant breast biopsy specimens to determine the prevalence and distribution of immunoreactivity with antibodies specific for the three mammalian isoforms of TGF-beta (beta 1, beta 2, and beta 3). We found that intense staining for TGF-beta 1 was positively associated with rate of disease progression, and that this was independent of age, stage, nodal status, or estrogen receptor status (P = 0.009). PMID- 1458486 TI - Disruption of mitochondrial function by suramin measured by rhodamine 123 retention and oxygen consumption in intact DU145 prostate carcinoma cells. AB - Suramin, an antiparasitic drug, has shown antitumor activity in humans. This may occur in part through disruption of energy balance, which is believed to be part of its antiparasitic action. Suramin disrupts mitochondrial function in intact DU145 prostate carcinoma cell monolayers as seen by its causing the release of rhodamine 123 from prestained cells beginning at about 10 microM in 96-well microtiter plates measured with a fluorescent plate scanner. This effect was similar to the ionophore carbonyl cyanide m-chlorophenylhydrazone, dissolved in ethanol at 0.01 N and indicates that suramin acts as a respiratory poison or an ionophore. This effect was confirmed by studies of oxygen consumption with a Clark oxygen electrode and cellular ATP content which demonstrated uncoupling of oxidative phosphorylation by 100 microM suramin, a clinically achievable plasma drug level. PMID- 1458487 TI - Growth suppression mediated by transfection of p53 in Hut292DM human lung cancer cells expressing endogenous wild-type p53 protein. AB - This study was undertaken to analyze the effect of wild-type p53 transfection on the growth potential of a human lung cancer cell line Hut292DM expressing endogenous wild-type p53. Transfection efficiencies obtained with either the wild type or a mutant p53 complementary DNA revealed a significant decrease in the number of colonies obtained with the wild-type p53 as compared to the mutant p53 complementary DNA (27%) or control vector DNA only (20%), suggesting that wild type p53 inhibited the growth of Hut292DM cells. A series of wild-type and mutant p53 transfection clones were then analyzed for the presence and expression of the exogenous p53 gene. Polymerase chain reaction amplification revealed that 98% of mutant p53 transfection clones analyzed contained the exogenous p53 gene as opposed to 47% for wild-type p53 clones. The majority of mutant p53 clones expressed high levels of exogenous p53 mRNA and protein as analyzed by Northern and Western blots, respectively. In contrast, all wild-type p53 clones analyzed failed to express exogenous p53 mRNA transcript or protein of a normal size. Aberrant-size p53 mRNA was detected in two wild-type p53 clones (X833.W2 and W18), and Western blot analysis revealed that these clones expressed truncated p53 proteins (M(r) 45,000 and 33,000 respectively). No difference in proliferation rates in vitro or in tumorigenic potential in nude mice were observed between mutant p53 clones or control cell lines. In contrast, a wild type p53 clone (X833.W2) exhibited a significantly reduced tumorigenic potential in nude mice, whereas its in vitro proliferation rate was comparable to parental Hut292DM cells. The data indicate that exogenous expression of wild-type p53 is incompatible with Hut292DM lung cancer cell proliferation in vitro and suggest that p53-mediated growth control in vitro and in vivo may be dissociated and exerted by separate domains of the p53 protein. PMID- 1458488 TI - Expression and regulation of the leukemia inhibitory factor/D factor gene in human T-cell leukemia virus type 1 infected T-cell lines. AB - The expression of the leukemia inhibitory factor/D factor (LIF) gene in human T cell leukemia virus type 1 infected T-cell lines was examined. Human T-cell leukemia virus type 1 infected T-cell lines MT-1, MT-2, H89-59, H89-79, and H109 expressed LIF mRNA, but the T-cell lines MOLT-4 and TALL-1 did not. LIF mRNA expression was enhanced by interleukin 2 or 12-O-tetradecanoylphorbol-13-acetate in MT-2 cells. The biological activity of LIF was detected in culture medium enhanced by interleukin 2 in MT-2 cells. The expression of LIF mRNA was suppressed by 1 alpha,25-dihydroxyvitamin D3 and dexamethasone. These results imply that the expression of the LIF gene is involved in the development of hypercalcemia and abnormalities of the immune system observed in patients with adult T-cell leukemia. PMID- 1458490 TI - A functional screen for germ line p53 mutations based on transcriptional activation. AB - Germ line p53 mutations represent a genetic predisposition for cancer development. At the present time, their detection requires extensive work and their functional significance must be documented. Therefore, we have designed a simple biological assay which detects functionally significant germ line p53 mutations. This assay is based on the cloning of the patient's p53 complementary DNA into a eukaryotic expression vector followed by the cotransfection into human cells of the recombinant vector with a reporter plasmid for the transcriptional activity of p53. This assay potentially offers a powerful method to screen fibroblasts or lymphocytes from patients for germ line mutations which inactivate the p53 tumor suppressor gene. PMID- 1458489 TI - Differential display and cloning of messenger RNAs from human breast cancer versus mammary epithelial cells. AB - Identification of the genes that are specifically expressed in tumor cells but not in normal cells (oncogenes), or vice versa (tumor suppressor genes), is important for understanding the molecular basis of cancer. The differential display technique was applied to compare mRNAs from normal and tumor-derived human mammary epithelial cells, cultured under the same conditions. Complementary DNA fragments corresponding to several apparently differentially expressed mRNAs were recovered and sequenced. They exhibit characteristics of the 3' end of eukaryotic mRNA, as predicted by the method. A complementary DNA fragment seen only in the normal cell was used as a probe to isolate its corresponding complementary DNA clone from a library. Northern analysis confirmed its differential expression. Thus, this method can be used for detecting, cloning, and sequencing of genes that are unique to a host of biological and disease processes. PMID- 1458491 TI - Lack of T-cell immunity in humans with preexisting anti-mouse immunoglobulin reactivity. AB - We have identified five normal individuals without known exposure to mouse immunoglobulin with "preexisting" human anti-mouse antibody (HAMA) against a panel of four mouse monoclonal antibodies and polyclonal mouse IgG. Competitive inhibition by polyclonal mouse IgG of HAMA binding to monoclonal antibody coated beads demonstrates the mouse constant region specificity of these sera. Lack of such inhibition by polyclonal human IgG eliminates polyclonal rheumatoid factors as an explanation. Lymphoblastic transformation studies in these five persons failed to demonstrate a memory T-cell response to the four mouse monoclonals or polyclonal mouse IgG. Positive controls included T-cell responses to streptolysin O in these five individuals as well as responses to monoclonal antibody D612 in three patients following treatment with that antibody. This lack of T-cell immunity to mouse IgG suggests that "preexisting" HAMA is the product of inadvertent cross-reactivity with murine constant region by antibodies directed against other antigens. Therefore, "preexisting" HAMA should pose no risk of anamnestic or allergic response in patients considered for murine monoclonal therapy. PMID- 1458492 TI - Re: S. M. Bronstein et al. Efficient repair of O6-ethylguanine, but not O4 ethylthymine or O2-ethylthymine, is dependent upon O6-alkylguanine-DNA alkyltransferase and nucleotide excision repair activities in human cells. Cancer Res., 52: 2008-2011, 1992. PMID- 1458493 TI - Regarding some aspects of the positive and negative effects of ionizing and medical treatment of pediatric brain tumors. PMID- 1458494 TI - Observations on electrical stimulation of lumbosacral nerve roots in children with and without lower limb spasticity. AB - Selective functional posterior rhizotomy (SFPR) is a popular operation for the treatment of spasticity in children with cerebral palsy, but the physiologic basis of the procedure is poorly understood. As part of SFPR operations in 60 consecutive children, the responses to electrical stimulation of posterior lumbosacral roots and rootlets, and the corresponding anterior roots were studied. In addition, similar electrical stimulation of posterior roots was performed in four nonspastic "control" children. Sustained responses to 50 Hz stimulation, one of the criteria used to signify abnormality in the spastic children, was found frequently in the "control" children. Contralateral spread to the lower limb muscles and suprasegmental spread to the upper limbs, face, and neck were determined to be the most valid criteria which differentiated abnormal from normal responses. Stimulation of anterior nerve roots at 50 Hz caused sustained responses and ipsilateral lower limb spread, at a low threshold compared to that of corresponding posterior roots. The results of this study bring into question the validity of some of the criteria that are used to select abnormal posterior rootlets in the SFPR procedure, and suggest criteria that may be more valid based on findings in nonspastic children. PMID- 1458496 TI - Congenital spinal cord astrocytomas. AB - Congenital spinal cord astrocytomas have only rarely been reported. We report two additional cases and a review of the literature on these infrequent tumors. The congenital cord astrocytomas can have obscure initial presentations, including fever and irritability, leading to delays in diagnosis. Magnetic resonance imaging is the diagnostic procedure of choice, allowing noninvasive delineation of the lesion. The congenital tumors are similar in location and pathology to astrocytomas of the cord in older children. As in older patients, initial treatment should include attempted surgical extirpation, delaying or avoiding radiation therapy with its attendant risks. Reported follow-ups of the congenital astrocytomas suggest they will behave in a fashion similar to spinal cord astrocytomas in older children. PMID- 1458495 TI - Central neurocytoma: its differentiation from intraventricular oligodendroglioma. AB - Two patients with intraventricular tumours are presented. Both had similar features on light microscopic examination. On the basis of the specific immunohistochemical staining patterns and the ultrastructural findings, one was diagnosed as a central neurocytoma while the other was diagnosed as an intraventricular oligodendroglioma. The possibility of central neurocytoma should be considered in all young patients including children presenting with an intraventricular lesion. Definitive diagnosis requires electron microscopic and immunohistochemical studies. PMID- 1458497 TI - Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW/Jms. AB - Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct. PMID- 1458498 TI - Expanding cranioplasty for craniosynostosis and allied disorders. AB - For early correction of craniosynostosis in the newborn or in early infancy, strip craniectomy may produce satisfactory results. For late correction, however, more radical cranial reconstruction procedures are essential in order to achieve adequate remodeling of cranial deformities and normalization of intracranial pressure. Craniosynostosis presents various types of cranial deformity, and different procedures for its correction have been reported. Expanding cranioplasty is presented for the increase of cranial volume and immediate correction of the cranial deformity. This cranioplasty can be applied not only for late correction of various types of craniosynostosis but also for other cranial deformities. PMID- 1458499 TI - Management of brain abscess in children: review of 130 cases over a period of 21 years. AB - The data on 130 children with brain abscesses treated over 21 years (1970-1990) were analyzed retrospectively. The whole group included four infants. Chronic ear infection and cyanotic congenital heart disease were the most common predisposing factors. In infants, meningitis and/or ventriculitis were dominant in the etiopathogenesis. Cases were evaluated according to the treatment received and also according to time periods. More than half of the patients (n = 74) in this series were treated by primary or secondary excision. Computed tomography (CT) facilitated the diagnosis and helped the planning of treatment. Aspiration gained increasing credit after the advent of CT. Microorganisms could be identified in 54% of the cultured specimens. Staphylococci, streptococci and Proteus were the dominating microorganisms. Penicillin and chloramphenicol have long been the mainstay of antimicrobial therapy but have recently been replaced by third generation cephalosporins and sulbactam-ampicillin combinations. Overall mortality was 15.5% but showed a decline from 30% in the pre-CT era to 6% in the last 5 years and to zero in the last three. Neither the location nor associated heart disease contributed to the mortality, but mortality among infants was as high as 50%. PMID- 1458500 TI - Perioperative rifampin/trimethoprim in cerebrospinal fluid shunt surgery. Comments on the paper by B. C. Walters et al., published in Child's Nerv Syst (1992) 8:253-257. PMID- 1458501 TI - New head-prone position for posterior fossa surgery in infants with severe hydrocephalus. AB - A new head-prone position is described for posterior cranial fossa surgery on infants whose cerebral cortical mantle has been markedly thinned by severe hydrocephalus. The new position furnished a direct line of sight to the apex of the IV ventricle corresponding to that provided by the classic high sitting position, without the latter's risks of air embolism and of acute subdural hematoma secondary to tearing of corticodural bridging vessels due to escape of gravity-impelled CSF from the large ventricles. The anesthesiologic technique, the positioning of the patient, and the surgeon's posture presented no unusual problems. PMID- 1458502 TI - Congenital cerebral venous dysgenesis. Decreased cerebral blood flow in deep cerebral regions revealed by SPECT. AB - This report describes a rare case of primary cerebral venous dysgenesis in a 3 year-old child with development retardation. Angiography resulted in nonvisualization not only of deep cerebral veins but also of superficial cerebral veins. In computed tomography and in magnetic resonance imaging the collateral venous circulation appeared as a strange configuration in the pineal region. Single photon emission computed tomography using N-isopropyl-p-[I-123] iodoamphetamine revealed decreased regional cerebral blood flow in the basal ganglia and thalamus, but cerebral infarction was not detected in the area. These features indicate that in this case, dysgenesis of deep cerebral veins, which probably occurred during prenatal life, had caused hypoperfusion in the deep cerebral regions. PMID- 1458503 TI - Vertebrobasilar infarcts in infancy: a case report and review of the literature. AB - We report a rare case of a child with cerebellar infarction confirmed by vertebral angiography, computed tomography and magnetic resonance imaging. The etiology of this case is unknown. The relevant literature is reviewed. PMID- 1458504 TI - Alcohol acts to promote incidence of tumors. AB - Alcohol is a major cancer risk factor. A variety of roles in carcinogenesis have been assigned to ethanol. Our recent studies indicate that ethanol may act as tumor promoter. Further studies suggest that ethanol may act as tumor promoter through free radicals generated during its metabolism because an increase in tumors was observed under conditions in which ethanol-induced lipid peroxidation could take place and not in which such lipid peroxidation could not occur. Other possibilities include ethanol effect on cell necrosis and cell proliferation and generation of a secondary mutagenic event through a DNA repair deficiency. The immune system, because it is a defense mechanism against carcinogenesis and because ethanol is immunosuppressive, must also play a role. Our current studies are aimed at elucidating some of these mechanisms and pointing out the complexity of the mechanisms that are affected by ethanol and that may be involved in tumor promotion. PMID- 1458505 TI - Food habits and esophageal cancer: an overview. AB - Cancer of the esophagus has a more varied geographical distribution and incidence than any other commonly occurring cancer. Its incidence rate is increasing in many countries, especially among males. Esophageal cancer has been found to be associated with the consumption of alcohol and tobacco, particularly when combined, and in the last decade the role of nutrition and diet in the etiology of this disease has attracted worldwide attention. Regions with a large incidence of this disease are generally located in poor parts of the world, and their inhabitants share several dietary characteristics. They subsist on a diet high in starch and almost without fresh fruit or vegetables, eat rapidly without sufficient mastication, and consume many foods (rice gruel) and drinks (tea) at very high temperatures. Hard and scratchy foods also are consumed frequently. In the high-risk region of northern Iran, where the frequency of esophageal cancer is higher among women than men, the main food during pregnancy contains strong black pepper and sharp crushed pomegranate seeds, which irritate the esophagus. PMID- 1458506 TI - Epidemiological study of French uranium miners. AB - An epidemiological cohort study has been carried out to demonstrate any excess cancer mortality in a group of French uranium miners who worked underground for at least 2 years. The latency period of cancer associated with this type of professional exposure was long (10 to 20 years). The first study includes miners who began underground mining between 1946-1972. The individual monthly exposure to radon and its decay products has been recorded since 1956. The exposure of the first 10 years had to be estimated retrospectively for each miner regarding the working conditions. Problems associated with these two different exposure recordings are discussed. The results revealed an excess of lung cancer mortality for miners who had begun underground mining during the years 1946-1956. PMID- 1458507 TI - The effects of iodinated glycerol, trichlorfon, and acetaminophen on tumor progression in a Fischer rat leukemia transplant model. AB - Sixty-day bioassays of iodinated glycerol, trichlorfon, and acetaminophen were conducted using a leukemia transplant model in 6- to 8-week-old F344 rats to investigate the potential of these chemicals to affect tumor progression. The chemicals were administered in the drinking water at doses that approximated those used in previously conducted 2-year carcinogenesis studies. Simultaneous with dose administration, half of a group of young, healthy, syngeneic rats were given subcutaneous transplants of mononuclear cells derived from spleens of leukemic donors. Variables used to quantitate tumor progression included body weight, spleen weight, white blood cell (WBC) and red blood cell (RBC) counts, packed cell volume, hemoglobin concentration, and platelet counts. Iodinated glycerol at 1.25 or 2.5 mg/ml caused a greater increase in leukocytosis in dosed transplant recipients in comparison to that experienced by undosed recipients: trichlorfon at 2.5 or 5.0 mg/ml enhanced splenomegaly and induced greater reductions in RBC parameters in dosed recipients in comparison to that experienced by undosed recipients. Acetaminophen at 3.0 and 6.0 mg/ml resulted in insignificant but dose-related increases in spleen weight and leukocytosis only in the female rat transplant recipients, as was observed in 2-year studies. Based on results from the short-term leukemia transplant model, data from 2-year carcinogenicity studies, and structure-activity considerations, exposure to iodinated glycerol and trichlorfon was more strongly associated with the expression of leukemia than exposure to acetaminophen. The potential carcinogenicity of each of these chemicals should be taken into consideration when calculating estimates of risk and decisions for their use. PMID- 1458508 TI - Detection of N-myc gene amplification in bone marrow specimen of stage IV neuroblastoma patients. AB - N-myc gene amplification is an unfavorable prognostic factor in neuroblastoma; therefore, its detection might have therapeutical consequences. Because of the reliability of noninvasive diagnostic methods such as X-ray examination and measurement of vanilymandelic acid and the lack of technical unavailability at most institutions, the determination of the N-myc status of neuroblastoma often is not done. In our investigation of 14 neuroblastoma patients, we could demonstrate N-myc gene amplification in the bone marrow of 5 patients with neuroblastoma stage IV disease and in bone marrow infiltration without enrichment of neuroblastoma cells. Otherwise, no information about the tumor content of N myc gene copies at the time of initial diagnosis could be obtained. At the subsequent resection, the N-myc gene amplification was confirmed by the additional Southern blot analysis and in situ hybridization of tumor tissue. Furthermore, the N-myc status of bone marrow was analyzed during the stages of chemotherapy in three cases. PMID- 1458509 TI - Descriptive analysis of the tumor registry experience for malignant melanoma from 1977 to 1986 at the University of Miami School of Medicine/Jackson Memorial Hospital. AB - A descriptive analysis was performed of malignant melanoma data ascertained by the University of Miami School of Medicine/Jackson Memorial Hospital (UM/JMH) Tumor Registry. A total of 376 melanoma cases were collected and reviewed. Most of the melanoma lesions occurred on the trunk, especially in the 40- to 49- and 50- to 54-year-old age groups. Local-stage cases had the best 5-year survival- 77%. The difference in survival between local-stage case and regional- and distant-stage cases was statistically significant (p = 0.0000). In males with local-stage disease, lesions on the trunk were associated with better survival than lesions at other sites (p = 0.04). In females with local-stage disease, survival was 68% for 5 years for trunk sites vs. 87% for other sites (p = 0.05). In local-stage disease, the overall 5-year survival was 85%. PMID- 1458510 TI - Promoting dietary change in the Stockholm Cancer Prevention Program. AB - The Stockholm Cancer Prevention Program (SCPP) is a community-based program aimed at reducing cancer incidence and mortality by reducing risk factors related to life-style: dietary habits, tobacco use, and sunbathing. The program, which came about as a result of a political initiative and commitment, has as its dietary objectives to reduce fat intake to 30% of energy and to increase fiber intake to 30 g/day. SCPP strives to achieve these goals by simultaneously affecting food supply and food demand. To date, the program collaborates with 12 municipalities and several large occupational health services and restaurant chains. It has developed cook books for caterers and the general public and has organized food fairs targeting policymakers and those working with food, education, or health promotion. SCPP emphasizes collaboration across sectors of society and has initiated contests for students studying food service technology and for retailers with the aim of promoting dietary change. The intervention is based on the principles and strategies of community organization. PMID- 1458511 TI - Effects of opioid peptides on the tumoricidal activity of spleen cells from nude mice with or without tumors. AB - The present study was designed to explore the effects of opioid peptides on the immune systems of intact nude mice and nude mice bearing human ovarian cancer cells (KF). When spleen cells from intact nude mice were incubated with medium alone, a significant ability of spleen cells to lyse the KF cells was not observed. However, incubation of the spleen cells with 1 microM beta-endorphin or 1 microM alpha-endorphin induced a significant lytic activity on the KF cells. The control-level lytic activity was increased significantly to about 4.5-fold by 1 microM beta-endorphin and about 3.7-fold by 10 microM met-enkephalin. These results suggest that opioid peptides play a crucial role in cellular immunity. Thus, we examined plasma levels of beta-endorphin in patients with ovarian or uterine carcinoma. The plasma beta-endorphin levels in patients with ovarian or uterine carcinoma were significantly higher (more than twofold) than those of age matched healthy women. PMID- 1458512 TI - Clonal karyotypic aberrations in enchondromas. AB - Enchondromas, benign cartilaginous tumors arising within the medullary cavity of bone, are frequently difficult to differentiate from their malignant counterpart. In this study, cytogenetic analysis was performed on seven cases of solitary enchondroma. Normal karyotypes were observed in five cases. Clonal abnormalities were detected in two cases. An isochromosome of the short arm of chromosome 6 characterized one case, and t(12;15)(q13;q26) in addition to random numerical and structural abnormalities such as telomeric association was observed in the other case. An i(6p) and structural rearrangements involving 12q13 previously have been described in chondrosarcoma. Our findings suggest that similar clonal karyotypic abnormalities exist in benign and malignant cartilaginous neoplasms. PMID- 1458513 TI - Sister chromatid exchange (SCE) frequency in lymphocytes of patients with colorectal carcinoma treated with razoxane. AB - The increased risk of neoplasia following cytotoxic therapy for both malignant and nonmalignant disease is well known. Sister chromatid exchange (SCE) frequencies in patients receiving such chemotherapy are often elevated, and the persistence of high levels after treatment may provide an indicator for susceptibility to secondary neoplasia. The cytostatic drug razoxane has been used for the treatment of psoriasis, acute myeloid leukemia (AML), and colorectal carcinoma. Prolonged use of this drug, however, has been associated with the subsequent development of AML and, up to November 1987, 16 cases of acute leukemia following razoxane treatment have been reported. We report the SCE frequencies for 34 patients with colorectal carcinoma who were receiving or had previously been treated with razoxane. Our results show no significant increase in SCE levels in the razoxane group compared with either normal controls or untreated patients. PMID- 1458514 TI - Immunocytochemical detection of oncoproteins in animal and human tumor lines with acquired or inherent multidrug resistance. AB - In this presentation, we analyze the relationship between protein expression of the protooncogenes c-fos, c-erb B1, c-K-ras, and c-myc and acquired or inherent multidrug resistance (MDR) in a panel of animal (CHO, S 180, L 1210) and human (KTCTL 44, KTCTL 18, CX 1, CXF 94) tumor lines by means of immunocytochemistry. Increased expression of c-fos and c-erb B1 proteins is a constant feature of all resistant cell lines except L 1210 cells, which did not reveal any alteration in oncoprotein expression. No apparent relationship between c-K-ras and c-myc proteins and MDR was found. The immunocytochemical results were corroborated by radioimmunoassays (RIAs). The data indicate that c-fos and c-erb B1 might play a role in the development of MDR. PMID- 1458515 TI - Early detection of colorectal cancer: a profile of current practice. AB - This study examines the prevalence of colorectal cancer screening among individuals in the general community. The survey was undertaken as part of a large scale general population survey of health practices and attitudes. A sample of 1090 people aged 40 years and over with no previous history of colorectal cancer or other predisposing condition was interviewed. Only 56% of this group reported that they regularly checked their bowel movements, the toilet bowl, or the toilet paper for signs of rectal bleeding. Only 13% could recall a doctor ever advising them to check for rectal bleeding; and 21% could recall a doctor asking them if they had ever noticed blood in their bowel movements. More involved practitioner-based procedures, such as digital rectal examination, fecal occult blood testing, endoscopy, and barium enema, were reported by only a minority of participants. Analysis of screening rates in the 9.3% of people who reported a family history of colorectal cancer revealed that this higher risk group was no more likely to be screened than those at average risk. PMID- 1458516 TI - Compliance with guidelines for mammography screening. AB - The health belief model was used to identify potential variables related to intention or compliance with mammography guidelines. Scales to measure independent and dependent variables were developed from previous research and assessed for validity and reliability. A probability sample of women 35 and older (x = 50) who resided in a large metropolitan area and surrounding counties (n = 322) participated in in-home interviews. Intent to complete mammography was related to having a family history of breast cancer, perceived barriers to mammography, and perceived control over breast cancer. Compliance with mammography was influenced by general health motivation and perceived susceptibility to and seriousness of breast cancer, benefits, and control over breast cancer. In addition, knowledge about breast cancer and breast cancer detection, age, having a health care provider suggest mammography, having symptoms of breast cancer, and socioeconomic status were significantly related to actual compliance with mammography. PMID- 1458518 TI - The perfusion pattern in coronary artery occlusion: comparison of exercise and adenosine.p6. AB - This study compared exercise to adenosine thallium-201 single photon emission computed tomography in detecting occlusion of left anterior descending or right coronary arteries in patients with no previous myocardial infarction. There were 41 patients who underwent adenosine thallium imaging (adenosine infusion at a rate of 140 micrograms/kg/min for 6 min), and 143 patients who underwent exercise thallium imaging. There were more patients with right coronary than left anterior descending coronary artery occlusion. Thus, in the adenosine group, there were 15 patients with left anterior descending artery occlusion, and 26 with right coronary artery occlusion, and in the exercise group, there were 46 patients with left anterior descending artery occlusion, and 97 patients with right coronary artery occlusion. In the adenosine group, the thallium images were abnormal in 41 patients (100%), while in the exercise group, the thallium images were abnormal in 125 patients (87%, P < 0.02) in the territories of the occluded arteries. ST segment depression was noted in 19 patients (46%) in the adenosine group, and 69 patients (48%) in the exercise group (P:NS). In patients with isolated single vessel occlusion, the size of the perfusion abnormality was 28 +/- 9% with adenosine, and 21 +/- 12% with exercise (P:NS). Thus, most patients with occlusion of the left anterior descending or right coronary artery have regional perfusion abnormality during stress; the different role of collaterals with each type of stress may explain the higher percentage of abnormal results with adenosine than exercise. PMID- 1458517 TI - Combined differentiation therapy in myelodysplastic syndrome with retinoid acid, 1 alpha,25 dihydroxyvitamin D3, and prednisone. AB - The myelodysplastic syndrome (MDPS) provides an opportunity for identifying host factors (genetic, endocrine, immune) involved in initiation and progression of preleukemia into frank acute myeloid leukemia. The aim of this study was to identify bone marrow (BM) cellular and humoral dysfunctions central to the development of MDPS and useful in therapeutic follow-up studies. Our preclinical studies have shown that (1) the characteristic stromal cell composition of the normal BM microenvironment was impaired in MDPS and in AML in 67 and 86% of the cases, respectively; (2) the 1 alpha,25(OH)2D3 concentration in BM plasma was abnormal in 50% of MDPS and 30% of AML; and (3) an inverse correlation existed in MDPS between the 1 alpha,25(OH)2D3 concentration and the frequency of F-CFU, (r = 0.41, p < 0.02), suggestive of a regulatory interaction between this secosteroid hormone and BM stromal cells. The analysis of clonal extinction of BM blast cells in response to all trans retinoic acid (RA), 1 alpha,25(OH)2D3, and colony stimulating factors (PHA-LCM), either alone or in various combinations, revealed individual patterns of responses in the cases of MDPS or AML. The results indicate the necessity for preclinical studies to select patients for combined differentiation therapy. Our ongoing clinical trials suggest that RA (Roaccutan, 20 mg/day continuously) as induction therapy, followed at weeks 6 to 8 by prednisone (40 mg/day for 15 days) and 1 alpha,25(OH)2D3 (Rocaltrol, 3 x 0.25 micrograms/day for 3 months) may induce a long-lasting hematological remission in MDPS. PMID- 1458519 TI - Use of sideholes for diagnostic coronary arteriography by Judkins technique in patients with ostial coronary stenosis. AB - Patients with ostial left main coronary artery stenosis are at increased risk from diagnostic cardiac catheterization. In order to reduce this risk a modified Judkins coronary catheter with a sidehole 1.5-2 cm from the tip has been used in 6 patients in whom pressure damping was observed after initial use of a standard end-hole Judkins left coronary catheter. This eliminates damping and allows forceful hand injection with good proximal and distal vessel opacification. It also allows the acquisition of multiple views without the need for catheter removal after each injection, thereby reducing the risk involved in multiple cannulations of a vessel with a potentially unstable lesion at its origin. The technique has also been used for ostial lesions in a right coronary artery and a vein graft. PMID- 1458520 TI - Cardiac catheterization laboratory survey: 1990. Society for Cardiac Angiography and Interventions, Laboratory Performance Standards Committee. AB - A survey of 117 member cardiac catheterization laboratories was undertaken by the Society for Cardiac Angiography and Interventions. The survey included numbers and types of procedures, both diagnostic and interventional, in adult as well as pediatric age groups. Radiation safety, various laboratory policies, frequency of short stay, and outpatient procedures were tabulated. Report generation, training programs, administrative organization, and laboratory equipment were all included. The results were compared with a 1978 survey. Areas of concern in terms of safety of the patient and possible underutilization of laboratories were identified. PMID- 1458521 TI - Early coronary artery stent restenosis: utility of percutaneous coronary angioscopy. AB - Restenosis of an endovascular stent may be caused by thrombus, intimal hyperplasia, or extrinsic compression. Angiography may not adequately define the etiology of restenosis. We describe a patient in whom angioscopy proved important in diagnosing intimal hyperplasia obviating the need for thrombolytic therapy and prolonged anti-coagulation. PMID- 1458522 TI - Early postoperative occlusion of a left internal mammary artery bypass graft with subsequent restoration of patency. AB - Total occlusion of a left internal mammary artery (LIMA) bypass graft is a rare complication, and reversal of a documented occlusion has not been reported. This is a case of an early postoperative occlusion of a LIMA graft that was found to be patent 4 months later. A patient with three vessel disease (including a moderate lesion in the proximal left anterior descending artery and a severe lesion in its mid-portion) underwent coronary artery bypass grafting with a LIMA to the mid-left anterior descending artery (LAD) and saphenous vein grafts to the right coronary and left circumflex arteries. Coronary angiography 3 months after surgery revealed a totally occluded internal mammary artery and saphenous vein grafts. The patient then underwent a successful angioplasty of the more distal lesion in the LAD. She subsequently returned with recurrent angina. Repeat coronary angiography revealed rapid progression of the disease in the proximal LAD with the more distal angioplasty site being widely patent. Selective arteriography of the internal mammary artery at that time revealed a patent vessel. Thus, the internal mammary graft is a physiologically active conduit that is dependent on flow dynamics. Competitive flow through the nonobstructive native LAD in combination with impedance of flow through the internal mammary artery due to a severe lesion in the LAD distal to the anastomosis led to a functionally occluded LIMA. When the obstruction in the proximal LAD progressed and the distal obstruction was successfully angioplastied, the flow dynamics in the internal mammary improved, allowing for its dilatation and restoration of patency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458523 TI - Coronary perforation during angioplasty: angiographic detection and demonstration of complete healing. AB - A patient is presented with localized perforation of the left anterior descending artery secondary to angioplasty balloon rupture. Despite a remarkable angiographic picture of coronary tear and dye extravasation into the surrounding pericardial tissue, the patient remained hemodynamically stable, and was medically treated. Five years later she redeveloped angina, and repeated coronary arteriography revealed complete healing of the perforation site. This case attests to the remarkable ability of the coronary artery to completely heal from a major wall trauma. Although a rare complication of coronary angioplasty, perforation can occur, and various management aspects should be considered. PMID- 1458524 TI - Failure of endocardial biopsy from the internal jugular vein due to endocardial scar: a new indication for the femoral venous approach. AB - Following cardiac transplantation, patients undergo serial endomyocardial biopsies to evaluate rejection, usually by the internal jugular approach. A case report and data are presented that demonstrate that this approach becomes less efficient and occasionally impossible in the third year after transplant (53% success rate per biopsy attempt) as compared to the first year after transplant (80%) probably due to the development of endocardial scar in the area sampled by the bioptome. Alternatively, one can change to the femoral venous approach which continues to have a high success rate in the third year after transplant (83%) because a different area of the interventricular septum is sampled when this approach is used. PMID- 1458525 TI - Interpretation of cardiac pathophysiology by waveform analysis: adult congenital anomalies. AB - Congenital anomalies are unusual in adults, but characteristic hemodynamic data facilitate precise diagnoses. A complete evaluation, including assessment for intracardiac shunts, is usually indicated in patients prior to major surgical procedures or electrophysiologic interventions. PMID- 1458526 TI - Collagen application for sealing of arterial puncture sites in comparison to pressure dressing: a randomized trial. AB - One hundred patients undergoing routine diagnostic or interventional catheterization were randomly assigned to receive either percutaneously applied collagen (group A; n = 50) or conventional pressure dressing (group B; n = 50) for sealing of the femoral artery. Clinical variables were comparable in both groups. The heparin dose was 100 IU/kg in 30 patients and 200 IU/kg in 20 patients of either group. The average compression time was 4.3 min in group A and 42.3 min in group B (p < .001). Bleeding was not observed in group A but was observed in 6/50 patients in group B. The time to ambulation was 6.4 hr (range, 4 12 hr) in group A and 21.6 hr (range, 10-48 hr) in group B (p < .001). Hematomas with a diameter of > 6 cm developed in 4/50 patients in group A and in 11/50 patients in group B (p < .05). Blood-transfusions or surgical interventions were not required and there was no loss of ankle pulses in either group. In conclusion, percutaneously applied collagen reduced compression time and duration of bedrest after diagnostic catheterization and PTCA. Despite earlier ambulation, the incidence of bleeding was lower with collagen than with conventional pressure dressing. PMID- 1458527 TI - PTCA with side-by-side balloon using fixed guide wire systems: a potential alternative autoperfusion device--an in vitro study. AB - The use of "hugging balloons" for the implementation of a coronary angioplasty is a well-known and much-written-about technique. It has not, on the other hand, ever been stressed that two inflated hugging balloons are not totally obstructive, leaving enough space, between the balloons and the arterial wall, for perfusion. The cross section of this free area can be as much as 12% of the total arterial cross section, when the side-by-side balloons are of a relatively similar size. Calculations show that similar total conduit cross sections are achieved when inflating either a 3.0 balloon or two 2.0 side-by-side balloons. An in vitro experiment compares how systems using 2.0 double balloons and a 3.0 autoperfusion balloon affect the distal flow of a 3 mm internal diameter conduit. A semi-rigid silastic tubing is perfused with a 5% glucose isotonic solution at various predetermined proximal pressure levels. Distal pressures and flows are measured at different stages: with no balloon, with deflated balloons, and with inflated balloons. Comparison shows that 1) the double balloon system offers little resistance to flow compared to the autoperfusion balloon; 2) this system's rate of perfusion run-off is hardly affected and is constantly better than with the autoperfusion balloon; 3) this difference is all the more marked, the lower the proximal perfusion. These results suggest that the use of a double balloon could, in some cases, provide an alternative solution to autoperfusion equipment. Further clinical studies are needed to test this hypothesis. PMID- 1458528 TI - The Tracker catheter: a new vascular access system. AB - Technologic advances in dilation equipment have been important in improving angioplasty success rates and in expanding the indications of dilation. Despite these improvements, approximately 7% to 10% of attempted dilations may ultimately fail because of inability to cross the culprit lesion. As angioplasty techniques are applied to an increasingly complex cohort of patients, the ultimate success of a given procedure depends more and more on the ability of the operator to select the appropriate equipment for a given procedure. We report the unique application of a commercially available perfusion catheter which may improve patient outcome during complex angioplasty. PMID- 1458529 TI - Mitral balloon valvuloplasty with transesophageal echocardiography without using fluoroscopy. AB - Balloon mitral valvuloplasty with Inoue technique was performed in two group of patients. In group I (n = 40) valvuloplasty was performed under fluoroscopy without using echocardiography, whereas in group II (n = 13) valvuloplasty was performed under the guidance of transesophageal echocardiography alone, without using fluoroscopy. Patients in two groups were comparable with regard to clinical variables and hemodynamic parameters. Two female patients in group II were pregnant. Transmitral pressure gradient decrease did not differ significantly between two groups (pressure gradient: 17 +/- 5 to 4 +/- 1 in group I and 15 +/- 4 to 3 +/- 1 mm Hg in group II). Mitral valvular area increase was also not different in two groups (1.09 +/- 0.2 cm2 to 2.3 +/- 0.5 cm2 in group I and 0.9 +/- 0.2 to 2 +/- 0.3 cm2 in group II). In 14 cases from group 1 and 2 cases from group II mitral regurgitation increased after valvuloplasty (p < .05). Left atrial perforation occurred in one patient from group 1 and 2 patients from group II. In conclusion, mitral balloon valvuloplasty under transesophageal echocardiographic guidance alone is a safe and effective procedure in the treatment of mitral stenosis. PMID- 1458530 TI - Rotational atherectomy in anomalous coronary arteries. AB - We describe two cases of high speed rotational atherectomy performed in patients with anomalous coronary anatomy. These procedures are performed with standard equipment requiring no modifications using a percutaneous femoral approach. We feel these cases clearly illustrate the facile application of this new technology to unusual anatomical situations. PMID- 1458531 TI - Improved support for right coronary artery angioplasty with a new guiding catheter. AB - Inadequate guiding catheter support is a frequent cause for failure in right coronary angioplasty (PTCA). A new guiding catheter designed to provide easy placement in the right coronary and improved stability and backup support is described. Use of this catheter for PTCA of right coronary lesions, the majority of which were considered technically difficult to dilate, in 100 patients resulted in successful dilatations in 88% of patients. Failures were due to inability to seat the guide adequately in 8 patients with narrow aortic roots or unusual coronary origins and to inability to cross a lesion in 4 patients despite good support. In 4 patients successful dilatation was achieved after failure using another presently available guide. PMID- 1458532 TI - Missing arteries? PMID- 1458533 TI - The TATA-binding protein and associated factors are components of pol III transcription factor TFIIIB. AB - RNA polymerases I, II, and III require the TATA-binding protein (TBP) to initiate promoter-specific transcription. We have separated HeLa TBP into four phosphocellulose fractions that elicit polymerase specificity in supplying TBP activity to TBP-depleted pol II and pol III transcription reactions. Polymerase specificity might arise in part through distinct TBP-associated factors (TAFs), which have recently been identified in pol I and II transcription. However, the requirement for pol III TAFs has not been established. Here we show that classical pol III transcription involves a minimum of two novel TAFs: TAF-172 and TAF-L. Not only does TAF-172 activate pol III transcription, but it also inhibits the binding of TBP to the TATA box, thereby repressing pol II transcription. The TBP-TAF-172-TAF-L complex can replace TFIIIB both in transcription reactions reconstituted with TFIIIC and in template commitment assays. Thus SL1, TFIID, and TFIIIB might be functionally similar TBP-TAF complexes that direct pol I, II, and III transcription, respectively. PMID- 1458534 TI - A TBP complex essential for transcription from TATA-less but not TATA-containing RNA polymerase III promoters is part of the TFIIIB fraction. AB - The TATA box-binding protein TBP directs transcription by all three eukaryotic RNA polymerases. In mammalian cells, TBP is found in at least three different complexes: SL1, D-TFIID, and B-TFIID. While SL1 and D-TFIID are involved in RNA polymerase I and II transcription, respectively, no unique function has been assigned to the B-TFIID complex. Here we show that the TFIIIB fraction required for RNA polymerase III transcription contains two separable components, one of which is a TBP-containing complex that may correspond to B-TFIID. For transcription of TATA-less RNA polymerase III genes such as the VAI, 5S, and 7SL genes, this complex cannot be replaced by either TBP alone or the D-TFIID complex. In contrast, TBP alone is active for basal transcription from the TATA containing U6 promoter. This indicates different requirements for recruiting TBP to TATA-less and TATA-containing RNA polymerase III promoters. PMID- 1458535 TI - Mechanism of TATA-binding protein recruitment to a TATA-less class III promoter. AB - The TATA-binding protein (TBP) is required for transcription by RNA polymerase III (pol III), even though many pol III templates, such as the adenovirus VA1 gene, lack a consensus TATA box. We show that TBP alone does not form a stable, productive interaction with VA1 DNA. However, it can be incorporated into an initiation complex if the other class III basal factors, TFIIIB and TFIIIC, are also present. TFIIIB can associate with the evolutionarily conserved C-terminal domain of TBP in the absence of DNA or TFIIIC, suggesting that TFIIIB exists in solution as a complex with TBP. The stable association of TBP with an essential component of the pol III transcription apparatus may account for the ability of TATA-less class III genes to recruit TBP. PMID- 1458536 TI - The role of the TATA-binding protein in the assembly and function of the multisubunit yeast RNA polymerase III transcription factor, TFIIIB. AB - The Saccharomyces cerevisiae RNA polymerase III transcription factor (TF)IIIB has been assembled from three components. An assembly pathway of these polypeptides, which specifies their interactions, has been determined. The TATA-binding protein, TBP, and the TFIIB-related BRF1 gene product BRF, together reconstitute the transcription factor activity and TFIIC-dependent DNA-binding activity of the B' component of TFIIIB. BRF alone weakly binds to a TFIIIC-tRNA gene complex; TBP greatly stabilizes this interaction. B" transcription factor activity is recovered with its previously identified 90 kd polypeptide from SDS polyacrylamide gels. Incorporation of the 90 kd B" protein into the transcription complex requires TBP. The heparin-resistant TFIIIB-DNA complex retains all three of its constituent proteins, TBP, BRF, and B". PMID- 1458537 TI - Xeroderma pigmentosum, Cockayne's syndrome, helicases, and DNA repair: what's the relationship? PMID- 1458538 TI - Focal adhesion kinase (p125FAK): a point of convergence in the action of neuropeptides, integrins, and oncogenes. PMID- 1458539 TI - Molecular parasitology at Woods Hole. PMID- 1458540 TI - A Drosophila model for xeroderma pigmentosum and Cockayne's syndrome: haywire encodes the fly homolog of ERCC3, a human excision repair gene. AB - The haywire gene of Drosophila encodes a protein with 66% identity to the product of the human ERCC3 gene, associated with xeroderma pigmentosum B (XP-B) and Cockayne's syndrome (CS). XP is a human autosomal recessive disease characterized by extreme sensitivity to ultraviolet irradiation and marked susceptibility to skin cancer. In addition, XP and CS patients often exhibit a variety of defects, ranging from central nervous system disorders to hypogonadism. Phenotypes of haywire mutants mimic some of the effects of XP. Many haywire alleles are recessive lethal, viable alleles cause ultraviolet sensitivity, and files expressing marginal levels of haywire display motor defects and reduced life span. Progeny of females carrying a maternal effect allele show central nervous system defects. PMID- 1458541 TI - Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. AB - Transgenic mice were generated that expressed a human collagenase transgene in their lungs under the direction of the haptoglobin promoter. Histological analysis demonstrated disruption of the alveolar walls and coalescence of the alveolar spaces with no evidence of fibrosis or inflammation. This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process. Although elastase has been proposed as the primary enzyme responsible for emphysematous lung damage, this study provides evidence that other extracellular matrix proteases could play a role in emphysema. In addition, these transgenic mice are a defined genetic animal model system to study the pathogenesis of emphysema. PMID- 1458542 TI - Isolation of a stem cell for neurons and glia from the mammalian neural crest. AB - We have isolated mammalian neural crest cells using a monoclonal antibody to the low affinity NGF receptor, and established conditions for the serial propagation of these cells in clonal culture to assess their developmental potential. This analysis indicates that, first, single mammalian neural crest cells are multipotent, able to generate at least neurons and Schwann cells like their avian counterparts. Second, multipotent neural crest cells generate multipotent progeny, indicating that they are capable of self-renewal and therefore are stem cells. Third, multipotent neural crest cells also generate some clonal progeny that form only neurons or glia, suggesting the production of committed neuroblasts and glioblasts. Manipulation of the substrate alters the fate of the multipotent cells. These findings have implications for models of neural crest development in vivo, and establish a system for studying the generation of cellular diversity by a multipotent stem cell in vitro. PMID- 1458543 TI - Polymer-bound enzyme inhibitors: synthesis, properties, and physiological relevance. AB - For the most part, the pharmacological effect of an enzyme inhibitor results from its interaction with a single target molecule--the target enzyme. In many cases, the inhibitor moiety can interact effectively with the enzyme without necessarily being released from the polymer carrier. In the simplest form, i.e., the inhibition of an extracellular enzyme, this interaction can be understood as being two macromolecules in a solution--a reaction that can be readily modeled in vitro. Thus, enzyme inhibitors are very suitable for preparing polymer-bound drugs for investigative purposes or therapeutical applications. The macromolecular properties of polymers impact on the pharmacokinetic behavior of the compound because of the controlled intercompartmental transport. The physiological significance of the polymer-bound enzyme inhibitors is considered herein regarding the factors controlling the biodistribution of polymers among the physiological compartments. Extracellular proteinases and lysosomal enzymes are the most easily approachable targets. Strategies for preparation of polymer bound inhibitors are discussed. PMID- 1458544 TI - Block copolymers as drug carriers. AB - The main subject of this review is to describe the concept and strategy of utilizing block copolymers as drug carriers and to present a perspective for this utilization. The first section points out preferable properties of block copolymers as drug carriers with a brief survey on classifications and synthesis of block copolymers and specifies the merits of block copolymers for this purpose in the historical background of polymeric drug carriers. The second section introduces several studies using block copolymers as drug carriers. These studies contain surface modification of microspheres with block copolymers, polymeric micelles, and a conjugate of an antibody and block copolymer. In conclusion, it is determined that block copolymers possess a high potential for use as drug carriers irrespective of some difficulties in their synthesis. PMID- 1458545 TI - The uses and properties of PEG-linked proteins. AB - Poly(ethylene glycol) (PEG) is a water soluble polymer that when covalently linked to proteins, alters their properties in ways that extend their potential uses. PEG-modified conjugates are being exploited in many different fields. The improved pharmacological performance of PEG-proteins when compared with their unmodified counterparts prompted the development of this type of conjugate as a therapeutic agent. Enzyme deficiencies for which therapy with the native enzyme was inefficient (due to rapid clearance and/or immunological reactions) can now be treated with equivalent PEG-enzymes. PEG-adenosine deaminase has already obtained FDA approval. PEG-modified cytokines have been constructed and, interestingly, one of the conjugates, PEG-modified granulocyte-macrophage colony stimulating factor, showed dissociation of two biological properties. This novel observation may open new horizons to the application of PEGylation technology. The biotechnology industry has also found PEG-proteins very useful because PEG enzymes can act as catalysts in organic solvents, thereby opening the possibility of producing desired stereoisomers, as opposed to the racemic mixture usually obtained in classical organic synthesis. Covalent attachment of PEG to proteins requires activation of the hydroxyl terminal group of the polymer with a suitable leaving group that can be displaced by nucleophilic attack of the epsilon-amino terminal of lysine residues (other nucleophilic groups can also interact). Several chemical groups have been exploited to activate PEG, thereby giving rise to a variety of PEG-proteins. Some of these varieties retain part of the activating group as a coupling moiety between PEG and protein and others provide a direct linkage. For each particular application, different coupling methods provide distinct advantages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458546 TI - Skin absorption enhancers. AB - When we try to maximize drug flux through the skin, we usually meet major difficulties because of the impervious nature of the stratum corneum. A popular solution incorporates penetration enhancers into transdermal products. Such materials ideally possess the sole property of reversibly reducing the barrier resistance of the horny layer, allowing the drug to reach the living tissues at a greater rate. This article considers examples of accelerant action that support a general concept explaining enhancer activity in human skin. The core of the proposal is that enhancers usually work by one or more of three main mechanisms: alteration of the lipid or protein domains of the stratum corneum or increase in tissue partitioning of a drug, a coenhancer, water, or any combination of these three chemicals. We may usefully refer to the overall hypothesis as the lipid protein-partitioning (LPP) concept. PMID- 1458547 TI - DNA-directed aniline mustards based on 9-aminoacridine: interaction with DNA. AB - A series of 4-substituted aniline mustards ArNH(CH2)nOpC6H4N(CH2CH2Cl)2, where Ar is an acridine and n varies from 2 to 5, interact with DNA. Scatchard analysis shows the compounds bind tightly, with a binding site size similar to that of 9 aminoacridine. The rate of hydrolysis of the mustards, measured by HPLC, is essentially constant across the series. With increasing length of the polymethylene linker, non-covalent binding becomes less strong, but the rate of DNA alkylation increases. Viscometric helix extension measurements and electrophoretic analyses using closed circular supercoiled DNA show that all the compounds are DNA intercalating ligands. Despite these similarities, the compounds are known to have quite different patterns of DNA alkylation, switching from guanine to adenine alkylation as the chain length is extended. PMID- 1458548 TI - Isotopically sensitive regioselectivity in the oxidative deamination of a homologous series of diamines catalyzed by diamine oxidase. AB - The equivalence of aminomethylene groups in selected diamine substrates of diamine oxidase was exploited for the determination of intramolecular isotope effects. In the series of substrates, [1,1-2H2]-1,3-diaminopropane, [1,1-2H2]-1,5 diaminopentane, [1,1-2H2]-1,6-diaminohexane, [1,1-2H2]-1,7-diaminoheptane and [alpha,alpha-2H2]-4-(aminomethyl)benzylamine, the preference of the enzyme for reaction at the unlabeled methylene was found to vary from 1.45 to 10.5-fold. The observed partitioning ratios go through a minimum value with 1,5-diaminopentane, the best substrate of diamine oxidase of the compounds tested. The results suggest that fast substrates have less opportunity to reorient into alternate binding conformations while bound to the active site of the enzyme. On the other hand, diamine substrates tested that cannot exist in energetically favorable conformations with internitrogen distances of about 7-8 A showed larger intramolecular isotope effects. PMID- 1458549 TI - Sphingosine induced release of K+ and 5-HT in platelets should not be confused with membrane leakiness. AB - The release of 43K+, lactate dehydrogenase (LDH) and [14C]-5-hydroxytryptamine ([14C]-5-HT) from platelets treated with sphingosine and four differently charged model amphiphiles was studied. Sphingosine was found to differ from the detergents because it induced a concentration-dependent release of both 43K+ and [14C]-5-HT without causing a release of LDH. The release of [14C]-5-HT preceded the release of 43K+ and it is concluded that these effects are associated with platelet activation. The detergents caused a release of 43K+ followed by a release of LDH without causing a release of [14C]-5-HT. These effects are attributed to a non-specific perturbation of the platelet plasma membrane. PMID- 1458550 TI - The involvement of selenium in peroxisome proliferation caused by dietary administration of clofibrate to rats. AB - The effects of dietary treatment with clofibrate (0.5% w/w for 10 days) on the livers of selenium-deficient male rats were examined. The peroxisome proliferation (as determined by electron microscopy) in the livers of selenium deficient animals was much less pronounced than in the case of selenium-adequate rats and no increase in peroxisomal fatty acid beta-oxidation (assayed both as antimycin-insensitive palmitoyl-CoA oxidation and lauroyl-CoA oxidase activity) was observed in the deficient animals. On the other hand, in selenium-deficient rats clofibrate caused increases in the specific activity of microsomal lauric acid omega- and omega-1-hydroxylation and an apparent change in mitochondrial size, seen as a redistribution of mitochondria from the 600 x g(av) pellet to the 10,000 x g(av) pellet, which were approximately 50% as great as the corresponding effects on control animals. Obviously, then, these three different effects of clofibrate are not strictly coupled and may involve at least partially distinct underlying mechanisms. Initial experiments demonstrated that peroxisome proliferation could be obtained by exposing primary hepatocyte cultures derived from selenium-deficient rats to clofibric acid (an in vivo hydrolysis product of clofibrate which is the proximate peroxisome proliferator), nafenopin or mono(2 ethylhexyl)phthalate. This finding suggests that selenium deficiency does not have a direct influence on the basic process(es) underlying peroxisome proliferation, but rather has indirect effects, influencing, for example, the pharmacokinetics of clofibrate and/or hormonal factors. PMID- 1458552 TI - Ultrasonic diagnosis of oral and neck malignant lymphoma. AB - A series of 14 patients with nodal and extranodal non-Hodgkin's lymphoma of the oral and neck region was analyzed by ultrasonogram evaluation. Eight nodal lymphomas and six extranodal lymphomas commonly exhibited almost completely similar ultrasonographic findings, specifically, clear delineation of the boundary echo and a homogeneous, weak internal echo, the so-called pseudo-liquid like images. The results derived from our study suggest that ultrasonic diagnosis is also helpful in evaluating patients with lymphoma during the initial diagnosis and initial treatment like other diagnostic imaging modalities. PMID- 1458551 TI - The mechanism of Hg2+ toxicity in cultured human oral fibroblasts: the involvement of cellular thiols. AB - To study amalgam-related toxicity in a primary target cell type, human oral fibroblasts were grown in a low-serum medium containing 1.25% fetal bovine serum and exposed to Hg2+, a corrosion product of amalgam. A 1-h exposure to various concentrations of Hg2+ resulted in a dose-dependent loss of colony forming efficiency. Removal of the low-molecular-weight thiol cysteine from the medium increased the toxicity of Hg2+ almost 50-fold in comparison with complete medium or medium without fetal bovine serum. Accordingly, fetal bovine serum was not found to contain detectable levels of low-molecular-weight thiols. The levels of cellular free protein thiols were shown to be depleted Hg2+ at significantly lower concentrations of the metal ion than those required to decrease the levels of the major cellular low-molecular weight thiol glutathione. These decreases were dependent on the exposure conditions, i.e. the presence of serum and thiols, in a manner similar to the effect on colony forming efficiency. Other functions commonly related to cell viability, including the accumulation of the vital dye neutral red, the cytosolic retention of deoxyglucose and the mitochondrial reduction of tetrazolium were also inhibited by Hg2+, albeit at higher concentrations. Finally, the depletion of cellular glutathione, by pre-exposure of the cells to the glutathione synthesis inhibitor buthionine sulfoximine, somewhat increased the toxicity of Hg2+ and potentiated the depletion of protein thiols. Taken together, the toxicity of Hg2+ in human oral fibroblasts was demonstrated in several assays of which colony forming efficiency was the most sensitive, cell killing by this agent was related to its high affinity for protein thiols, whereas glutathione showed a significant, but limited, ability to protect the cells from Hg2+ toxicity. PMID- 1458553 TI - Cardiotoxicity of mitomycin A, mitomycin C, and seven N7 analogs in vitro. AB - The alkylating antitumor agents mitomycin A (MMA), mitomycin C (MMC), and seven N7 analogs were compared in terms of their cardiotoxic and antitumor activity in vitro. Neonatal rat-heart myocytes were sensitive to five of the compounds studied, including MMA, 7-dimethylamidinomitosane (BMY-25282), 7-(N-methyl piperazinyl)-mitosane (RR-194), N7-(4-iodophenyl)-MMC (RR-208), and N7-(4 hydroxyphenyl)-MMC (M-83) in order of descending molar potency. MMA and RR-208 possessed the greatest cytotoxic potency against 8226 human myeloma tumor cells in vitro. Two of the nine mitomycins studied, BMY-25282 and M-83, showed greater cytotoxic potency for heart cells. For these two agents, the ratio of the 50% inhibitory concentration in heart cells to that in 8226 myeloma cells was 50 and 32, respectively. For the other analogs, the tumor-cell cytotoxic potency was much higher (ranging from 200 to 7,000). For the nine mitomycin compounds, a correlation was found between heart-cell toxicity and low reduction potentials (E1/2 values) ranging from -0.16 to -0.37 V. Thus, as the reduction potential decreased (easier reducibility), the cardiotoxic potency in vitro increased (r = 0.81). In contrast, mitomycins with reduction potentials of higher than -0.37 V were much less potent cardiotoxins. Thus, mitomycin C (E1/2 = -0.45 V) was noncardiotoxic even when tested at concentrations 100-fold above those pharmacologically achievable in humans. Mitomycin C also failed to enhance doxorubicin (Adriamycin) cardiotoxicity in vitro. Importantly, no correlation was found between the reduction potential and the antitumor activity of the nine analogs (n = 0.51), in this small series. PMID- 1458554 TI - Cell cycle-specific metabolism of arabinosyl nucleosides in K562 human leukemia cells. AB - Exponentially growing K562 cells incubated with 1-beta-D-arabinofuranosylcytosine (ara-C) accumulate ara-C triphosphate (ara-CTP) at a higher rate and to a greater concentration after pretreatment with 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-ara-A) than do cells treated with ara-C alone. Potentiation of ara-C metabolism is due in part to an indirect effect of F-ara-A triphosphate (F-ara ATP)-mediated reduction in deoxynucleotide pools and consequent activation of deoxycytidine kinase. Because the levels of deoxynucleotide pools and the activity of deoxycytidine kinase are cell cycle-specific, we investigated the effect of cell cycle phases on the accumulation of ara-CTP and the influence of F ara-A pretreatment on such accumulation. Exponentially growing K562 cells were fractionated into G1, S, and G2+M phase-enriched subpopulations (each enriched by > 60%) by centrifugal elutriation. The rate of ara-CTP accumulation was 22, 25, and 14 microM/h and the rate of F-ara-ATP accumulation was 38, 47, and 33 microM/h in the G1, S, and G2+M subpopulations, respectively. The rate of elimination of arabinosyl triphosphates was similar among the different phases of the cell cycle. After pretreatment with F-ara-A, the rate of ara-CTP accumulation in the G1, S, and G2+M phase-enriched subpopulations was 43, 37, and 26 microM/h, indicating a 1.7-, 1.5-, and 1.9-fold increase, respectively. These results suggest that a combination of F-ara-A and ara-C may effectively potentiate ara CTP accumulation in all phases of the cell cycle. This observation is consistent with the results of studies on the modulation of ara-C metabolism by F-ara-A in lymphocytes and leukemia blasts obtained from patients with chronic lymphocytic leukemia and acute myelogenous leukemia, respectively. PMID- 1458555 TI - Distribution of hexadecylphosphocholine and octadecyl-methyl-glycero-3 phosphocholine in rat tissues during steady-state treatment. AB - The distribution of the alkylphosphocholine hexadecylphosphocholine (He-PC) and the (alkyl)lysophospholipid 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (ET18-OCH3) was analyzed in rats. The compounds were given orally at a daily dose of 75 mumol/kg body weight. After 6, 11, and 18 days, three rats in each treatment group were killed and the drug concentration in various tissues and fluids was determined. With the exception of the kidney (He-PC) and brain (He-PC and ET18-OCH3), steady-state levels of the drugs could be achieved in all organs investigated and in serum. Maximal concentrations of He-PC were found in the kidney, adrenal glands, and spleen, whereas the highest concentrations of ET18 OCH3 were detected in the adrenal glands, spleen, and small intestine. The concentrations of He-PC exceeded those of ET18-OCH3 in most tissues by a factor of about 2-25. Since samples of urine and feces did not contain detectable amounts of the compounds, the absorption of both lipid analogues was assumed to be complete. The total amount of He-PC recovered after 6, 11, and 18 days was 15%, 12%, and 6%, respectively, and that of ET18-OCH3 was 1.3%, 0.8%, and 0.3%, respectively. This indicates that the bioavailability of He-PC and ET18-OCH3 is not controlled by differences in the uptake of the two drugs, but by differences in their metabolism. The results could explain the differing efficacy of these two compounds in their antitumor action in animal models. PMID- 1458556 TI - The role of NAD(P)H:quinone oxidoreductase in mitomycin C- and porfiromycin resistant HCT 116 human colon-cancer cells. AB - A mitomycin C (MMC)- and porfiromycin (PFM)-resistant subline of the HCT 116 human colon-cancer cell line was isolated after repeated exposure of HCT 116 cells to increasing concentrations of MMC under aerobic conditions. The MMC resistant subline (designated HCT 116-R30A) was 5 times more resistant than the parent cells to MMC and PFM under aerobic conditions. Both the MMC-resistant cells and the parent HCT 116 cells accumulated similar amounts of PFM by passive diffusion, but levels of macromolecule-bound PFM were about 50% lower in the resistant cell line, implying a decrease in PFM reductive activation in the resistant cells. The finding that microsomes from either sensitive or resistant cells showed an equal ability to reduce MMC and PFM indicated that the activity of NADPH cytochrome P-450 reductase (EC 1.6.2.4) was not changed in the resistant subline. Soluble extracts of HCT 116 cells reduced MMC and PFM more effectively at pH 6.1, and NADH and NADPH were utilized equally well as electron donors under both aerobic and anaerobic conditions. These data suggest that quinone reductase (EC 1.6.99.2; DT-diaphorase) in soluble extracts is responsible for the reduction of MMC. Quinone reductase activities in soluble extracts of HCT 116-R30A cells for the reduction of dichlorophenol indophenol (DCPIP) and menadione-cytochrome c at optimal pHs were decreased by 95% as compared with those obtained in parent cells. However, the MMC-reducing activity of HCT 116-R30A soluble extracts was only 50% lower than that of the parent cell extracts. The kinetic constants (Km, Vmax) found for quinone reductase in the two cell lines with respect to the substrates DCPIP and menadione differed. Two species of mRNA for quinone reductase (2.7 and 1.2 kb) were detected in both cell lines, and there was no detectable difference between parent and resistant cells in the steady-state level of either of these mRNA species. Furthermore, incubation with the quinone reductase inhibitor dicoumarol rendered HCT 116 cells more resistant to MMC. Alteration of the quinone reductase activity in HCT 116-R30A cells appears to be the mechanism responsible for their resistance to MMC and PFM. PMID- 1458557 TI - Intraperitoneal administration of the antitumour agent N-[2 (dimethylamino)ethyl]acridine-4-carboxamide in the mouse: bioavailability, pharmacokinetics and toxicity after a single dose. AB - The pharmacokinetics, tissue distribution and toxicity of the antitumour agent N [2-(dimethylamino)-ethyl]acridine-4-carboxamide (AC) were studied after i.p. administration of [3H]-AC (410 mumol/kg) to mice. The latter is the optimal single dose for the cure of advanced Lewis lung tumours. AC was rapidly absorbed into the systemic circulation after i.p. administration, with the maximal concentration (Cmax) occurring at the first time point (5 min). There was no reduction in bioavailability as compared with previous i.v. studies, but the shape of the plasma concentration-time profile was considerably different, reflecting a 3-fold lower Cmax value (20.9 +/- 3.6 mumol/l) and a longer t1/2 value (2.7 +/- 0.3 h) as compared with that observed after i.v. administration (1.6 +/- 0.6 h). Model independent pharmacokinetic parameters after i.p. administration were: clearance (C), 17.5 l h-1 kg-1; steady-state volume of distribution (Vss), 14.1 l/kg; and mean residence time (MRT), 1.46 h. High but variable tissue uptake of AC was observed, with tissue/plasma AUC ratios being 5.7 for heart, 8.4 for brain, 18.9 for kidney and 21.0 for liver but with similar elimination t1/2 values ranging from 1.3 to 2.7 h. All radioactivity profiles in plasma and tissues were greater than the respective parent AC profiles and showed prolonged elimination t1/2 values ranging from 21 h in liver to 93 h in brain. However, tissue/plasma radioactivity AUC ratios were near unity, ranging from 0.7 to 1.57, with the exception of the gallbladder (15.6), which contained greater amounts of radioactivity. By 48 h, approximately 70% of the total dose had been eliminated, with the faecal to urinary ratio being approximately 2:1. This i.p. dose was well tolerated by mice, with sedation being the only obvious side effect. No major change was observed in blood biochemistry or haematological parameters. Comparisons of Cmax, tmax and AUC values determined for AC in brain after its i.p. and i.v. administration suggest that the reduction in acute toxicity after i.p. administration is not due to reduced exposure of the brain to AC as measured by AUC but may be associated with the lower Cmax value or the slower rate of entry of AC into the brain after i.p. administration. PMID- 1458558 TI - Cyclosporin A potentiation of VP-16: production of long-term survival in murine acute lymphatic leukemia. AB - Our prior in vitro studies on the correction of multidrug resistance by cyclosporin A (CsA) prompted us to investigate the effect of CsA and VP-16 in vivo. CsA given simultaneously at 2 or 10 mg/kg with VP-16 to BDF/1 mice bearing parental drug-sensitive P388 or L1210 lymphatic leukemia produced a 100% increase in survival as compared with VP-16 treatment alone. CsA-containing regimens also promoted 60-day survival in a significant number of P388 or L1210 leukemia bearing mice as compared with animals receiving VP-16 in the absence of CsA (P < 0.02 and P < 0.001, respectively). CsA enhancement of the survival of mice bearing these lymphatic leukemias is restricted to VP-16, since the addition of CsA to therapeutic agents such as vincristine, daunorubicin, methotrexate, or cisplatin had no effect on survival. PMID- 1458559 TI - Distribution characteristics of mitoxantrone in a patient undergoing hemodialysis. AB - The pharmacokinetic profile of mitoxantrone in a patient undergoing hemodialysis is described. Significant characteristics of our patient included lymphoma with liver involvement, tumor lysis syndrome, renal and hepatic failure. Combination chemotherapy consisted of mitoxantrone, vincristine, and cyclophosphamide. Mitoxantrone plasma samples were obtained prior to dosing and at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.5, 7.0, and 12 h after the intravenous infusion of a 17-mg dose over 20 min. Serum concentrations were determined by high-performance liquid chromatography. The serum concentration versus time curve was consistent with a three-compartment model. However, rebounds in serum drug concentrations were detected during the last portion of dialysis and after its completion. The gamma elimination half-life could not be determined due to the continued detection of rebounds in drug concentrations throughout the postdialysis sampling period. The alpha and beta distribution phases did not appear to be affected by hemodialysis. The peak mitoxantrone concentration fell within the reported range. Mitoxantrone does not appear to be eliminated by hemodialysis, and dose adjustments are not needed in patients undergoing this procedure. PMID- 1458560 TI - Relationship between tumor cell density and drug concentration and the cytotoxic effects of doxorubicin or vincristine: mechanism of inoculum effects. AB - When tumor cell density increases, the cytotoxic activity of certain anticancer agents, such as vincristine (VCR) and doxorubicin (DXR), progressively decreases. This phenomenon is termed the inoculum effect. Since VCR and DXR are less active in an acidic environment, we questioned whether the inoculum effects could have resulted from acidification of the medium that may have developed due to the high cell density. However, measurements of the cytotoxic activity of these agents in a pH-controlled medium revealed only a minor correction of the inoculum effects. Second, we wondered whether the inoculum effects that occurred at the high cell density might have been attributable to insufficient amounts of drugs to bind all the binding sites of the cells. To test this hypothesis, we used drug-resistant sublines, which required higher VCR or DXR concentrations for cell killing than did the parent cell line. When higher drug concentrations were used, the dose response curves generated for low- and high-density cell populations became closer and overlapped each other, resulting in virtual disappearance of the inoculum effects. Measurements of cellular drug levels revealed that at a high cell density, cells accumulated much smaller amounts of both VCR and DXR in parallel with the positive inoculum effect. In contrast, when high concentrations of the drugs were used in drug-resistant cells, differences in the cellular drug contents between low and high cell densities became narrow. Cisplatin (DDP) belongs to a group of drugs that do not produce inoculum effects, and DDP's cytotoxic effects were not influenced by the pH-controlled medium or by the use of drug-resistant cell lines. These observations indicate that the inoculum effects are the result of the unavailability of VCR or DXR molecules to all cellular binding sites when cells at high densities are exposed to drugs. The drug concentration relative to cell density was apparently the major determinant for the inoculum effects seen in VCR- or DXR-induced cell killing. PMID- 1458561 TI - Mechanistic implications of alterations in HL-60 cell nascent DNA after exposure to 1-beta-D-arabinofuranosylcytosine. AB - To improve our understanding of the mechanism of 1-beta-D arabinofuranosylcytosine (ara-C) incorporation into DNA, we investigated the physical properties (size, position of nucleoside incorporation) of small fragments of nascent DNA (nDNA) obtained by pH-step alkaline elution of intact HL 60 cells following their exposure to ara-C. In the pH-step alkaline elution procedure, the smallest fragments of nDNA elute at pH 11. Anion-exchange high performance liquid chromatography (HPLC) of nDNA obtained by 1 h elution at pH 11.0 of lysed HL-60 cells revealed a preponderance of nDNA fragments ranging from 0.5 to 40 kb in control ([3H]-dThd-labeled) cells. Exposure of cells to ara-C (0.8-1 microM) resulted in a loss of the preponderance of radiolabel in fragments of 0.5-40 kb along with redistribution of the radiolabel (from [3H]-dThd or [3H] ara-C) into smaller nDNA fragments (predominantly < 100 bases in length) as determined by HPLC. We used the ability of pH-step alkaline elution to provide these small nDNA fragments produced by ara-C to investigate the paradoxical behavior of ara-C as a chain terminator in cell-free DNA synthetic systems while being incorporated into an internucleotide position in intact cells. Following the digestion of purified nDNA with micrococcal nuclease and spleen phosphodiesterase II, the proportion of radiolabel in 3'-dNMP (indicating an internucleotide position) or free nucleoside (indicating a chain terminus position) was determined by reverse-phase HPLC. In digests of prelabeled genomic DNA, as expected, > 90% of the radiolabel from [14C]-dThd or [3H]-ara-C was found to exist in an internucleotide position (as determined by co-chromatography with authentic 3'-dTMP or 3'-ara-CMP). In contrast, digests of nDNA that eluted at pH 11.0 revealed a significantly higher proportion of radiolabel in the chain terminus position (29%-35%) when the nDNA was obtained from cells exposed to 1 microM [3H]-ara-C as compared with cells exposed to [3H]-dThd or [3H]-dCyd alone (< 10%). These data obtained from pH-step alkaline elution of intact cells suggest that by causing the inhibition of chain elongation while failing to inhibit the formation of new nDNA replication intermediates, ara-C exposure leads to the production of very small nDNA fragments. This relative chain-terminating effect of ara-C is most apparent in the small nDNA replication fragments that elute at pH 11.0.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1458563 TI - Serum elimination half-life of tamoxifen and its metabolites in patients with advanced breast cancer. AB - In breast cancer patients discontinuing chronic tamoxifen therapy, the serum elimination of metabolites X, Y and E paralleled that of tamoxifen, whereas that of metabolite Z did not. The serum elimination of tamoxifen and metabolites X and B was increased by amino-glutethimide treatment, whereas that of metabolites Z, Y, and E was not. PMID- 1458562 TI - Protection against fludarabine neurotoxicity in leukemic mice by the nucleoside transport inhibitor nitrobenzylthioinosine. AB - Fludarabine phosphate (F-ara-AMP, Fludara) is rapidly converted in the circulation to fludarabine (F-ara-A) and is among the most effective single agents in the treatment of chronic lymphocytic leukemia. Although current treatment protocols are well tolerated, severe neurotoxicity was a consequence of high-dose F-ara-AMP regimens used in early phase I trials against adult acute leukemia. The present study showed that in mice implanted with leukemia L1210, fatal neurotoxicity, which initially manifested as hind-limb paralysis, was a consequence of high-dose F-ara-AMP treatment. However, the incidence of neurotoxicity was reduced by the coadministration of NBMPR-P, the 5'-phosphate of nitrobenzylthioinosine, a potent inhibitor of the es equilibrative nucleoside transport (NT) system. NBTGR-P, the 5'-phosphate of nitrobenzylthioguanosine (also a potent NT inhibitor) similarly prevented F-ara-AMP neurotoxicity in this experimental system. Treatment with F-ara-AMP/NBMPR-P combinations was more effective with respect to the fractional yield of "cured" mice than were the same treatment regimens without NBMPR-P. PMID- 1458564 TI - Adriamycin-induced inhibition of arachidonate incorporation into phospholipids of mastocytoma P815 cells. AB - Adriamycin inhibited [1-14C]-arachidonic acid uptake by mastocytoma P815 cells in a dose-dependent manner (5-120 nM). The incorporation of [1-14C]-arachidonic acid into phospholipids was decreased mainly into cardiolipin and phosphatidylcholine. PMID- 1458565 TI - Primary liver cancer in Hong Kong. AB - From 1984 to 1987, we conducted a series of chemotherapy trials to assess their efficacy and impact on survival in patients with inoperable hepatocellular carcinoma. A total of 18 patients were treated with etoposide at a dose of 200 mg/m2 given on days 1-3 every 3 weeks for a maximum of 8 courses. No response was observed in any of the 18 patients studied. A further trial using epirubicin at doses of 40 and 75 mg/m2 again showed no evidence of a tumor response in 14 consecutive patients. The dose of epirubicin was further escalated to 90 mg/m2. Of the 33 patients treated, 1 (3%) achieved a complete response and 2 (6%) showed a partial response. Although the overall median survival amounted to only 72 days, the survival of the three responders was 15, 13, and 12 months, respectively. Therefore, we believe that the tumor response to epirubicin may be dose-dependent. However, the toxicity was also dose-dependent. To improve the therapeutic index, we are currently evaluating the impact of intrahepatic arterial injection of a lipiodol-epirubicin emulsion. PMID- 1458566 TI - Liver transplantation in Taiwan: the Chang Gung experience. AB - Between March 1984 and February 1991, six orthotopic liver transplantations were performed at the Chang Gung Memorial Hospital in Taiwan. The indications for transplantation were Wilson's disease (5 patients) and biliary atresia (1 patient). Donors and recipients were matched only for size and ABO blood group compatibility, and the recipient operations were performed without the use of a venovenous bypass. Arterial reconstruction was carried out by end-to-end hepatic artery anastomosis (4), thoracic aortic conduit (1), or interposition of an iliac artery graft (1), whereas biliary reconstruction was accomplished by a choledochocholedochostomy using a T-tube stent (4) or a choledochocholedochostomy using an external cholecystostomy without stenting (2). Biliary complications occurred in three patients, and all required additional surgery. The average duration of donor-liver cold ischemia, operating time, and blood loss during surgery were 7 h and 50 min (range, 4.5-9 h), 13.5 h (range, 11.8-17 h), and 4,385 ml (range, 750-12,000 ml), respectively. The immunosuppressive regimens included a cyclosporin-steroid combination (n = 2) and a triple-drug combination (n = 4). All except one of the surviving patients experienced at least one rejection episode that was reversed by a methyl-prednisolone bolus and/or recycle. One patient developed a primary cytomegalovirus (CMV) infection that responded well to Ganciclovir treatment. Two of the patients died, one of injuries sustained in a traffic accident 3 years after transplantation, and the other of massive upper gastrointestinal bleeding. The overall survival value at 3 months was 83%, and the follow-up period ranged from 3 months to 7 years. All of the survivors have achieved complete rehabilitation and currently enjoy an excellent quality of life with normal liver function. Although the present study involved a small number of cases, our results indicate that liver transplantation can be successfully achieved in a high proportion of patients with acceptable morbidity, mortality, and cost in an Asian setting. The extreme shortage of donor organs is currently the most important obstacle limiting the application of liver transplantation in Taiwan. PMID- 1458567 TI - Management of patients with unresectable liver metastases from colorectal and gastric cancer employing an implantable port system. AB - Between 1985 and 1990, 50 patients with unresectable liver metastases from colorectal cancer and 34 subjects with metastases from gastric cancer were treated by repeated hepatic arterial infusion chemotherapy employing an implantable prot system. A catheter was inserted into the hepatic artery via the left subclavian artery and was connected to the implantable injection port in each patient. 5-Fluorouracil (5-FU) at 330 mg/m2 per week (167 mg/m2 daily given continuously over the initial 3 months for colorectal cancer), Adriamycin (ADR) at 20 mg/m2 every 4 weeks and mitomycin C (MMC) at 2.7 mg/m2 every 2 weeks were given to all 34 patients with gastric cancer and to 31 of the colorectal cancer patients. The remaining 19 patients with colorectal cancer received 5-FU at 1,000 mg/m2 every week. As a rule the treatment was performed on an outpatient basis. The side effects and complications observed included myelosuppression (23%), hepatic arterial occlusion (21%), and gastroduodenal mucositis (12%), although no major toxicity was encountered. The response rate (CR+PR) among the evaluated patients as determined using CT scans was 67% for colorectal cancer and 73% for gastric cancer. The overall median survival was 12 months and 15 months, respectively. Good local control of liver metastases from the colorectal and gastric cancers was achieved by repeated hepatic arterial infusion chemotherapy employing an implantable port system without the need for hospitalization and without producing major toxicity. Thus, the implantable port system is very useful for the management of patients with unresectable liver metastases. PMID- 1458568 TI - Standardization, calibration, and the care of diabetic patients. PMID- 1458569 TI - Interlaboratory study of the IFCC method for alanine aminotransferase performed with use of a partly purified reference material. AB - We present the results of a study on performance of a reference material for alanine aminotransferase (ALT, EC 2.6.1.2) and the corresponding IFCC-approved method in an interlaboratory trial involving 13 laboratories. The ALT material was partly purified from pig heart (specific activity, 150 kU/g) and was essentially free of six potentially contaminating enzyme activities, including aspartate aminotransferase (EC 2.6.1.1). The partly purified ALT was lyophilized in a triethanolamine-buffered matrix, pH 6.4, containing bovine serum albumin and saccharose. Under these conditions, the predicted yearly loss of activity was 0.02% at 4 degrees C and < 0.01% at -20 degrees C. The final blank-corrected results of the accepted set of data gave a mean (SD) of 128.5 (5.1) U/L. The among-laboratory SD was 4.6 U/L and the within-laboratory SD was 2.0 U/L. The certified ALT catalytic concentration in the reconstituted material was 129 U/L with a 0.95 confidence interval of +/- 4 U/L. PMID- 1458570 TI - Affinity binding assay of glycohemoglobin by two-dimensional centrifugation referenced to hemoglobin A1c. AB - We describe an automated assay of glycohemoglobin performed with the Abbott Vision analyzer. The assay is based on batch affinity-extraction with 3 aminophenylboronic acid-derivatized agarose beads. Reagents are packaged in a disposable test pack. Whole-blood specimens are hemolyzed with saponin within a glass capillary tube inserted into the test pack. The sample is automatically diluted with, mixed with, and separated from the solid-phase reagent. Bichromatic absorbance readings are used to calculate the percentage of hemoglobin bound. Based on the linear correlation between affinity-measured glycohemoglobin and HPLC-measured hemoglobin A1c, the percentage of hemoglobin bound is converted to a "standardized %HbA1c" result by use of regression parameters stored during a calibration run. The combination of affinity methodology with standardization by reference to HPLC produces values directly comparable with those obtained by methods specific for HbA1c. The method produces 10 results within 15 min. The assay operates with CVs < 5%, and the results correlate highly with those by ion exchange and affinity minicolumn methods, and by ion-exchange HPLC. PMID- 1458571 TI - Analytical and clinical evaluation of creatine kinase MB mass assay by IMx: comparison with MB isoenzyme activity and serum myoglobin for early diagnosis of myocardial infarction. AB - We analytically and clinically evaluated Abbott's IMx assay for creatine kinase (CK) isoenzyme MB (CK-MB) in serum. Over a 1-year period, the method was more specific but less precise than catalytic isoenzyme measurements by electrophoresis or immunoinhibition. Sera from different individuals without electrophoretic evidence of CK-MB but containing macro CK type 1 (n = 20), mitochondrial CK (n = 5), or CK-BB (n = 5) were scored as CK-MB negative by the IMx. Likewise, CK-MB-negative by the sera remained so after addition of purified human CK-MM (< or = 7600 U/L) or CK-BB (< or = 8100 U/L). For 39 patients admitted for suspicion of uncomplicated acute myocardial infarction (precordial pain for < or = 4 h), the diagnostic performance of the IMx CK-MB assay on admission and 4 h later was superior to that of total CK activity and compared well with that of CK-MB activity measured by electrophoresis or immunoinhibition. An admission, myoglobin showed a higher diagnostic sensitivity, specificity, and predictive value than did CK-MB and was the most informative test. Diagnostic performance on admission and 4 h later was further improved by considering positivity for myoglobin and for CK-MB by IMx and for the change in each over the first 4 h of hospitalization as criteria. Twelve hours after admission, diagnostic performance was further improved for all CK and CK-MB methods but began to decline for myoglobin. PMID- 1458572 TI - Apolipoprotein B quantified by particle-concentration fluorescence immunoassay. AB - We have developed a particle-concentration fluorescence immunoassay (PCFIA) for estimating apolipoprotein (apo) B concentrations in plasma. A two-step antigen detection system with a polyclonal antibody to apo B bound to carboxyl polystyrene particles binds the antigen, and a fluorescein-labeled monoclonal antibody detects the bound apo B. Narrow-cut low-density lipoproteins (d = 1.03 1.05 kg/L) were used as the primary standard. The assay compares well with the enzyme-linked immunosorbent assay. The PCFIA gives parallel responses with low density lipoprotein, very-low-density lipoproteins, and plasma samples, and can be fully automated and completed in 3 h. In a pilot study of patients with diabetes, coronary artery disease (CAD), or both, we found statistically significant differences in apo B concentrations for patients with both CAD and diabetes compared with those for patients with diabetes alone or for control subjects (P < 0.01). PMID- 1458573 TI - Use of synthetic H disaccharides as acceptors for detecting activities of UDP GalNAc:Fuc alpha 1-->2Gal beta-R alpha 1-->3-N-acetylgalactosaminyltransferase in plasma samples from blood group A subgroups. AB - Concentrations of blood group A-specified alpha(1-->3)-N acetylgalactosaminyltransferase (A enzyme) were measured in human plasma of blood groups A1, A2, and A3 by using chemically synthesized H disaccharides and H type 1 and type 2 trisaccharides attached to hydrophobic aglycones as acceptors. When the trisaccharides were used as acceptors, enzyme activities were reduced in samples from A2 and A3. However, the H disaccharides were shown to be good acceptors even for enzymes from A2 and A3, and no significant difference in enzyme concentration was detected in any of the plasma tested. PMID- 1458574 TI - Creatine kinase MB isoforms in patients with skeletal muscle injury: ramifications for early detection of acute myocardial infarction. AB - We measured total creatine kinase (CK), CK-MB isoenzyme, and the MB isoforms in 202 serum and plasma samples from nine groups of patients and normal individuals: 39 with acute myocardial infarction (MI), divided according to time between the onset of chest pain and blood collection (1-6 h, 7-12 h, and 13-48 h); 26 with chest pain for whom an MI was ruled out, sampled at admission; 17 undergoing bypass surgery or cardiac catheterization, sampled within 6 h after either procedure; 17 with acute skeletal muscle injury, sampled within 8 h after injury; 30 marathon runners immediately after a race; 17 runners and other athletes > 12 h after training or a race; 12 with cerebral injury or seizures, sampled at admission; 8 with closed head injury, sampled at admission; and 38 normal subjects. CK-MB (relative index) and MB isoforms (MB2/MB1) were respectively increased in 15% and 75% of MI patients 1-6 h after onset, 94% and 94% after 7-12 h, and 88% and 8% after 12 h, and in 87% and 82% of cardiac surgery patients. MB isoforms were increased in most patients with acute skeletal muscle trauma and in subjects examined after exercise, but were within normal limits in patients for whom MI was ruled out, patients with cerebral trauma, and normal individuals. The relative index of MB/total CK was normal in essentially all individuals in the last groups, including those with acute skeletal muscle trauma. We concluded that the CK-MB isoform ratio is increased in both acute skeletal muscle injury and MI. The isoform ratio is most useful for distinguishing recent from old (> 12 h) injury. PMID- 1458575 TI - Quantitative determination of methemoglobin by measuring the solvent-water proton nuclear magnetic resonance relaxation rate. AB - We report a new method for the quantitative determination of human methemoglobin (metHb) based on the measurement of the solvent-water proton-nuclear magnetic resonance (NMR) relaxation rate R1 [normalized to 1 mmol/L hemoglobin (Hb) concentration]. MetHb (%) is estimated from the linear dependence of R1 on the metHb concentration, taking into account the simple relationship [MetHb] = [(R1 - R1HbO2)/(R1metHb - R1HbO2)].100, where R1HbO2 and R1metHb are values for the solvent-water relaxation rate of standard 1.0 mmol/L solutions of the oxygenated derivative of human hemoglobin (HbO2) and of metHb, respectively. The minimum metHb that may be determined from the analysis of the experimental data is 0.5 +/ 0.4%. PMID- 1458576 TI - Standardization of glycohemoglobin determinations in the clinical laboratory: three years of experience. AB - Measurement of glycohemoglobin has been recommended for the long-term assessment of glycemic control in diabetic patients. Because different analytical methods measure different glycohemoglobin species, it has been difficult to compare results between laboratories. Here we report 3 years of experience with calibration of an affinity chromatography method for measuring total glycohemoglobin (GHb). Calibration was achieved by including in each assay three hemolysate calibrators for which values for HbA1c and GHb had been determined by repeated analyses by high-performance liquid chromatography (HPLC) and affinity chromatography, respectively. Calibration improved interassay precision (CV = 3.20-7.90% and < 5.0% before and after the introduction of calibration, respectively) and eliminated lot-to-lot variability. In 91 samples, HbA1c was estimated by the calibrated affinity chromatography assay and measured by an ion exchange HPLC method. Estimated and HPLC-measured HbA1c showed no clinically significant differences during 36 months. The high degree of long-term precision, the disappearance of lot-to-lot variability, and the excellent comparability between analytical methods measuring different species of glycated hemoglobins demonstrate the advantages of calibration. PMID- 1458577 TI - Discrepancies between sodium concentrations measured by the Kodak Ektachem 700 and by dilutional and direct ion-selective electrode analyzers. AB - We have identified rare (approximately 0.2% of all samples), but clinically significant, discrepancies between serum or plasma sodium concentrations measured with the Kodak Ektachem 700's direct ion-selective electrode (ISE) method and concentrations measured with two other analyzers: the Beckman Synchron CX3's dilutional ISE instrument and the Radiometer KNA2 instrument for sodium-potassium analysis by the direct ISE method. The differences do not appear to be related to any previously identified sources of discrepancy, such as variations in triglycerides, bicarbonate, total protein, albumin, or gamma-globulin, the presence of paraproteins, or interference by benzalkonium chloride from heparinized catheters. They occurred despite the use of Gen 04 reference fluid on the Ektachem. We could not identify any drug or family of drugs that the patients had taken in common and that might influence the results. Until this problem is resolved, Ektachem users should be aware of the potential for discrepancies of > 6 mmol/L in measurements of sodium concentrations. PMID- 1458578 TI - DNA diagnosis with mutation-specific artificial methylation sites: application to rapid screening of delta F508. AB - Many polymerase chain reaction (PCR)-based methods for diagnosis of minute mutations are suboptimal for automated screening because of their reliance on gel electrophoresis or probe hybridization. In the method reported here, PCR products containing artificial methylation sites are analyzed by measuring incorporation of radiolabeled methyl groups. Primers are designed to amplify the possible mutation-containing region such that the 3' end of one primer lies adjacent to the possible mutation. Sequence modification near that end creates either a mutation- or wild type (WT)-specific artificial methylation site in the PCR product. The product is briefly incubated with an appropriate DNA methylase and tritiated S-adenosylmethionine ([3H]SAM), separated from free SAM by column chromatography, and analyzed for incorporation of tritium. Applying this technique to the cystic fibrosis delta F508 deletion, we accurately diagnosed five homozygotes, five heterozygotes, and five normal individuals within 40 min of PCR completion. The method can be generalized to rapid, automated detection of a variety of point mutations and small deletions. PMID- 1458579 TI - Fluorescence polarization immunoassay and HPLC assays compared for measuring monoethylglycinexylidide in liver-transplant patients. AB - We compared fluorescence polarization immunoassay (FPIA, x) and HPLC (y) for measuring monoethylglycinexylidide (MEGX) concentrations in 119 serum samples from 61 liver-transplant donors and recipients. The correlation between the two methods was y = 1.48 micrograms/L + 0.8x (r = 0.89). The bias (mean difference) was 12 micrograms/L (0.055 mumol/L) through the MEGX concentration range measured (0-250 micrograms/L, 0-1.136 mumol/L). We observed a major difference between the two methods in samples from four recipients and one donor. Cross-reactivity in FPIA with lignocaine and two of its metabolites (glycinexylidide and 2,6 xylidine) was < 3%. Samples with high bilirubin concentrations (> 200 mumol/L) required dilution before assay of MEGX by FPIA. Although there was an increase in apparent MEGX concentrations in some samples with increased bilirubin concentrations, the relationship was not constant. Increased plasma concentrations of cholesterol and triglyceride resulted in relatively small increases in apparent MEGX concentrations. PMID- 1458580 TI - Lactate measured in diluted and undiluted whole blood and plasma: comparison of methods and effect of hematocrit. AB - We evaluated a new analyzer that measures lactate in undiluted whole blood by direct (or undiluted) amperometry [Nova Stat Profile 7 Analyzer (SP7); Nova Biomedical, Waltham, MA] by comparing it with two other analyzers, one for measuring lactate in whole blood by indirect (or diluted) amperometry [Model 2300; Yellow Springs Instrument Co. (YSI), Yellow Springs, OH] and another for measuring lactate in plasma by enzymatic colorimetry (aca; Du Pont Co., Wilmington, DE). All between-method comparisons of the three methods showed that the results for plasma were comparable (Sy/x = 0.24-0.33 mmol/L). Within-method comparisons by the YSI differed substantially between plasma and whole blood (Sy/x = 0.48 mmol/L), but within-method comparisons by the SP7 produced better agreement between plasma and whole blood (Sy/x = 0.18 mmol/L). The difference between whole blood and plasma by YSI is related to hematocrit, with the greatest differences noted for samples with the highest hematocrit. Serum lactate measured by SP7 had between-day imprecision (CV) ranging from 12% at 0.5 mmol/L to 4.2% at 3.7 mmol/L, showed a linear standard curve to at least 11.5 mmol/L, and was independent of hematocrit. There was a mean bias of approximately 0.4 mmol/L for results in the reference range for both plasma and whole blood by SP7 compared with plasma results by either aca or YSI. PMID- 1458581 TI - Direct determination of zinc in serum by Zeeman atomic absorption spectrometry with a graphite furnace. AB - We developed a precise and accurate graphite furnace atomic absorption spectrometric method for the direct determination of zinc in serum. Serum samples are analyzed after 20-fold dilution with water of ultrapure analytical grade. No other reagent is used, from the moment of sampling until measurement. During atomization, the argon flow is kept at 150 mL/min instead of gas stop, to decrease the sensitivity and thus allow lower dilution ratios. Zinc concentrations are determined against a serum-matched calibration curve. Graphite tubes are uncoated and no L'vov platform is used. Between-run CVs were 5.9%, 3.5%, and 1.9% for serum zinc concentrations of 0.93, 1.15, and 1.43 mg/L, respectively. The characteristic mass was 9 pg, and the detection limit (meanblank + 3SDblank) was 0.060 mg/L. PMID- 1458582 TI - Relation between magnesium and potassium concentrations in myocardium, skeletal muscle, and mononuclear blood cells. AB - Potassium and magnesium were measured in 26 cardiac surgery patients (right atrial appendage), 23 autopsy subjects (right atrial appendage, left ventricular free wall, and skeletal muscle), and 9 healthy volunteers (mononuclear blood cells) to determine whether there was a relation between these two ions in the tissues measured. In the cardiac surgery patients, the potassium and magnesium concentrations were 46.35 +/- 3.89 and 4.40 +/- 0.58 (mean +/- SD, mumol/g wet weight tissue), respectively, and were significantly correlated (r = 0.54, P = 0.005). In the autopsy group, the respective concentrations were: for right atrial appendage, 30.54 +/- 10.18 and 3.66 +/- 0.70 mumol/g (r = 0.38, P = 0.14); left ventricular free wall, 60.69 +/- 17.93 and 7.74 +/- 1.73 mumol/g (r = 0.92, P = 0.0001); and skeletal muscle, 93.05 +/- 20.49 and 8.64 +/- 2.06 mumol/g (r = 0.91, P = 0.0001). In the healthy volunteer group, the results for potassium and magnesium in mononuclear blood cells were 42 +/- 9.9 and 3.99 +/- 0.70 fmol/cell, respectively (r = 0.94, P = 0.0001). Thus, potassium and magnesium concentrations were significantly correlated in all the tissues measured. PMID- 1458583 TI - Studies of lipid peroxidation products in cerebrospinal fluid and serum in multiple sclerosis and other conditions. AB - Lipid peroxides were measured in cerebrospinal fluid (CSF) and sera from patients with multiple sclerosis (MS) or other conditions and from control subjects. In serum, visible fluorescence, A240nm, and free and protein-bound thiobarbituric acid (TBA)-reactive substances were significantly greater in MS patients than in control subjects. No such differences were observed in CSF. There was no correlation between lipid peroxides and disease severity or relapse time. We observed a significant positive correlation between CSF protein-bound TBA reactive substances and CSF protein, suggesting that production of the former depends on protein concentration. A significant negative correlation between free TBA-reactive substances in serum and ultraviolet fluorescence indicated that production of free TBA-reactive substances may be associated with decreased production of fluorescent lipid peroxides. This study provides evidence for increased lipid peroxidation in serum but not CSF from MS patients, suggesting that either there is no increase in CSF lipid peroxidation in MS patients or that CSF lipid peroxides are rapidly removed, possibly by binding to CSF proteins that can be reabsorbed into the blood. PMID- 1458584 TI - Reference values for immunoglobulin kappa and lambda light chains and the kappa/lambda ratio in children's serum. AB - We analyzed 708 serum samples from healthy children and adolescents by immunonephelometry to obtain reference values for the immunoglobulin kappa (kappa) and lambda (lambda) light chains and for their ratio at a time of life when immunoglobulin synthesis is maturing and continually being stimulated. The lambda chain concentration that is to be maintained throughout the child's life is reached very early, just after 1 year, whereas the concentration of the kappa chains, which increases gradually, reflects the concentration of the immunoglobulins as a whole. These reference values may be useful for studying kappa and lambda chains in illnesses involving the immune system in children. PMID- 1458585 TI - Determination of beta 2-microglobulin in serum by a microparticle-enhanced nephelometric immunoassay. AB - This fully automated nephelometric immunoassay to quantify beta 2-microglobulin in human serum measures the light-scattering signal produced by agglutination of commercially available latex microparticles (diameter 0.1 micron) coated with specific F(ab')2 against beta 2-microglobulin. The calibration curve, generated by serial dilutions of a beta 2-microglobulin standard of known concentration, is used to calculate beta 2-microglobulin concentrations in serum samples by the logit-log function and linear-regression analysis. The assay range (sample dilution 400-fold) extends from 0.3 to 40.0 mg/L. No antigen excess appears at beta 2-microglobulin concentrations up to 320 mg/L. Within-run CVs ranged from 1.0% to 3.4%, and between-days from 1.2% to 2.8%. Total imprecision (CV) was < 5%. Analytical recovery averaged 99.5% +/- 2.8%. Rheumatoid factor, complement, bilirubin (up to 340 mumol/L), and hemoglobin (up to 2.0 g/L) do not interfere. Strongly turbid lipemic samples must be cleared before analysis. Standard curve linearity was very good in samples covering the clinical useful range of concentrations. Results of the method correlated well with those of radioimmunoassay and microparticle enzyme-linked immunoassay (r = 0.979 and 0.975, respectively). The reference interval (nonparametric estimation) in apparently healthy adults (n = 303) was 0.87 (0.80-0.94) to 2.42 (2.28-2.45) mg/L; the median value was 1.54 mg/L. PMID- 1458586 TI - Measurement of free desipramine in serum by ultrafiltration with immunoassay. AB - We developed an ultrafiltration method for assaying free desipramine (DMI) in serum. An ultrafiltrate of DMI-containing serum was prepared by centrifugation through an Amicon Centrifree micropartition filter. Syva DMI solid-phase extraction (SPE) columns were used to extract the DMI from the serum and ultrafiltrate. The Syva monoclonal EMIT assay was used to quantify the DMI in the extract. In some experiments, the percent free DMI was quantified with radioactivity. Nonspecific losses of DMI in serum to the ultrafilter system were low (recoveries > 91%). Extraction of [3H]DMI from phosphate-buffered saline (to mimic serum ultrafiltrate) with the Syva SPE system was quantitative (recoveries of 98.4% +/- 4.6%). Free DMI concentrations, derived from serum containing 2.5 2500 micrograms/L DMI, were determined by ultrafiltration; results agreed well with values determined by equilibrium dialysis, the average percent of free DMI being 18.4% +/- 0.25% and 15.9% +/- 0.51%, respectively. To increase the sensitivity of the free DMI assay in the therapeutic range (total DMI 125-300 micrograms/L), we increased fourfold the ultrafiltrate volume applied to the SPE column. For free DMI at 11-130 micrograms/L, the within-run and between-run CVs for the ultrafiltration method were < 9% and < 15%, respectively. Binding of DMI to serum proteins decreased over the pH range 6.0-8.0, although temperatures between 20 and 28 degrees C did not affect binding. The ultrafiltration assay is fast, accurate, simple, and adaptable to standard laboratory instrumentation. PMID- 1458588 TI - Arsenic analysis II: rapid separation and quantification of inorganic arsenic plus metabolites and arsenobetaine from urine. AB - We describe the rapid separation of inorganic arsenic plus metabolites from arsenobetaine or seafood arsenic in urine. Traditional, high-pressure liquid chromatography is replaced by disposable silica-based cation-exchange cartridges for this separation. Both fractions are quickly separated and collected for analysis by atomic absorption spectrophotometry. Analytical recovery of both fractions is > or = 95%, with an overall precision (CV) ranging from 1.6% to 6.4%. Using this method, we correctly identified the sources of arsenic exposure, whether of inorganic or seafood origin, in 11 urine specimens supplied by the Centre de Toxicologie du Quebec. PMID- 1458587 TI - Interlaboratory standardization of measurements of glycohemoglobins. AB - The diversity of methods used to measure glycohemoglobins (GHb) makes it difficult to compare patients' results among laboratories. We reported previously the feasibility of providing comparable results from different assays by use of common calibrators. We here compare results from seven different GHb methods calibrated by use of hemolysates assayed by a precise ion-exchange high performance liquid-chromatographic (HPLC) method for hemoglobin A1c (HbA1c). Thus, regardless of the GHb species measured by the seven methods, results were referenced to the HbA1c content of the calibrators. Without this calibration, GHb values for single samples varied, e.g., from 4.0% to 8.1% and from 10% to 14.2% in the normal and high ranges, respectively. Calibration decreased between-method variability (single sample ranges of, e.g., 4.8% to 5.4% and 9.4% to 10.2% in the normal and high ranges, respectively) and improved interassay precision. We conclude that this approach to calibration of GHb measurements allows direct comparison of results obtained by different methods and improves precision. PMID- 1458589 TI - Recent developments in alkaline phosphatase research. PMID- 1458590 TI - Introduction: recent developments in alkaline phosphatase research. PMID- 1458591 TI - Perspectives in alkaline phosphatase research. AB - Gene cloning and site-directed mutagenesis have had a profound effect on alkaline phosphatase research. Four distinct structural genes encoding placental, intestinal, and tissue-nonspecific isoenzymes have been cloned, sequenced, and mapped to human chromosomes. Differences in properties between the respective gene products are due to variations in primary structure involving only one, or a few, key amino acid residues. Recognition that alkaline phosphatase belongs to the category of molecules that are localized to cell membranes through a COOH terminal glycan-phosphatidylinositol anchor provides a basis for understanding the generation of isoforms observed in plasma in disease. Isoforms produced by differential cleavage or preservation of the glycan-phosphatidylinositol anchor may offer new correlations with disease that are of diagnostic value. However, a more important contribution of alkaline phosphatase research to clinical chemistry may prove to be an increased understanding of disease processes at the molecular level. PMID- 1458592 TI - The two mRNAs encoding rat intestinal alkaline phosphatase represent two distinct nucleotide sequences. AB - Rat duodenal mucosa contains two mRNAs (2.7 and 3.0 kb) encoding intestinal alkaline phosphatase (IAP), but the mechanism for their production has not been clear. By means of the polymerase chain reaction (PCR), we isolated a fragment that identifies a second rat IAP (rIAP-II), differing from the rIAP-I sequence in the coding and 3' untranslated regions and encoding a COOH-terminal sequence predicted to be hydrophilic. By means of probes unique to each sequence, rIAP-I identified the 2.7-kb mRNA, and rIAP-II the 3.0-kb mRNA. The different structures and differential regulation of the mRNAs after fat feeding demonstrate the presence of two rat IAP transcripts. PMID- 1458593 TI - Placental alkaline phosphatase: a model for studying COOH-terminal processing of phosphatidylinositol-glycan-anchored membrane proteins. AB - Placental alkaline phosphatase (PLAP) has been used as a model for studying the biosynthesis of the phosphatidylinositol-glycan (PI-G)-protein linkage in intact cells and in cell-free systems. However, for the study of processing in cell-free systems, a small protein devoid of glycosylation sites is preferable. A PLAP derived cDNA was engineered that codes for a nascent protein (mini-PLAP) of 28 kDa in which the NH2- and COOH-termini are retained but most of the interior of PLAP is deleted. In vitro translation of mini-PLAP mRNA in the presence of rough microsomal membranes yields mature PI-G-tailed mini-PLAP. Processing of nascent mutant proteins occurs only when a small amino acid is located at the site of cleavage and PI-G attachment (omega site). Mutations adjacent and COOH-terminal to the omega site have revealed that the omega + 1 site is promiscuous in its requirements but that only glycine and alanine are effective at the omega + 2 site. Rough microsomal membranes from T cells deficient in PI-G biosynthesis do not support processing of mini-PLAP; addition of exogenous PI-G restores activity. Translocation of the proprotein, most likely requiring ATP and GTP, precedes COOH-terminal processing. PMID- 1458594 TI - Differential release of human intestinal alkaline phosphatase in duodenal fluid and serum. AB - Human intestinal alkaline phosphatase (IAP) can be released by the enterocyte into duodenal fluid as a mixture of three isoforms. A proportion of the enzyme is associated with triple-layered membrane vesicles (vesicular IAP). Although, occasionally, free hydrophilic IAP dimers are present, the remaining enzyme usually consists of a mixture of hydrophobic IAP dimers and more complex hydrophobic IAP structures of larger size, both entities being identified as "intestinal variant" alkaline phosphatase (VAR IAP). The hydrophobicity of VAR IAP stems exclusively from its attached glycosyl-phosphatidylinositol (GPI) anchor. Both vesicular IAP and VAR IAP are converted to hydrophilic enzyme upon removal of the GPI tail by phospholipase D (PLD) present in duodenal fluid. The IAP released into the vascular bed consists mainly of VAR IAP; vesicular IAP is absent. The enzyme characteristics of VAR IAP partially purified from duodenal fluid and from serum are identical. In plasma, VAR IAP appears to associate with (lipo)protein complexes and is thus protected from further degradation by plasma PLD. Such complex formation may explain why, in the serum of a healthy reference population, VAR IAP was more abundant than hydrophilic dimeric IAP. PMID- 1458595 TI - Chemical nature of intestinal-type alkaline phosphatase in human kidney. AB - Approximately 10% of the alkaline phosphatase activity in human kidney is derived from the intestinal-type alkaline phosphatase isoform, which can be differentiated from adult intestinal alkaline phosphatase by selective reactivity with monoclonal antibodies. The NH2-terminal sequence of the renal intestinal type alkaline phosphatase was shown to be identical to sequences of the adult and meconial alkaline phosphatases except for the NH2-terminal valine residue, which is missing in the renal intestinal-type enzyme. Incubation of purified meconial alkaline phosphatase with kidney homogenate resulted in removal of the NH2 terminal valine residue, indicating the presence of aminopeptidases in kidney that catalyze this hydrolysis. Furthermore, the oligosaccharide chains of the renal intestinal-type alkaline phosphatase were shown to differ from those of meconial and adult intestinal alkaline phosphatases, as revealed by lectin affinity chromatography. The heterogeneity of the intestinal-type alkaline phosphatase can therefore be generated both by partial peptide bond hydrolysis and differences in glycosylation. PMID- 1458596 TI - Placental alkaline phosphatase as the placental IgG receptor. AB - We review data from our studies of the physiological role of placental alkaline phosphatase (PLAP) and report that, in addition to functioning in catalysis, PLAP has the capacity to bind the Fc portion of human IgG. The dissociation constant for the interaction (3.86 mumol/L) indicates that the PLAP-IgG complex probably occurs in vivo. Furthermore, the electrophoretic and immunochemical properties of PLAP are identical to those of the purified placental Fc receptor. This receptor is believed to participate in the transfer of IgG molecules from the maternal circulation to the fetus during pregnancy. Studies with HEp2 cells show that PLAP is necessary for the internalization of IgG molecules. PLAP behaves, at least in this cell line, as an Fc receptor. The presence of large amounts of PLAP in clathrin-coated vesicles prepared from placenta strongly indicates that PLAP is involved in the endocytic machinery in this organ. We conclude that these results, taken together, suggest a novel biological role for PLAP. PMID- 1458597 TI - Alkaline phosphatase isoenzyme patterns in malignant disease. AB - Early treatment of patients with malignant disease and liver or bone metastasis may increase their survival time. We have used the activity patterns of liver and bone isoenzymes of alkaline phosphatase (ALP), separated by agarose gel electrophoresis, to detect early metastasis. We studied ALP isoenzyme patterns in a background population of 101 patients with no evidence of any disease that might influence this pattern; a healthy reference population (n = 330); and the following three groups of patients: 143 with malignant disease, 47 with nonmalignant liver disease, and 22 with nonmalignant bone disease. Cutoff and predictive values of liver ALP, high-molecular-mass (high-M(r)) ALP, and bone ALP were established for detecting liver and bone metastasis. The positive predictive value of liver and high-M(r) ALP was higher than that of total ALP in detecting liver metastasis, but liver and high-M(r) ALP did not enable us to differentiate between malignant and nonmalignant liver disease. Total ALP activity was of slightly more value than liver and high-M(r) ALP in enabling us to rule out liver metastasis. From bone ALP activity we could not distinguish between nonmalignant bone disease and bone metastasis. The negative predictive value of bone ALP in the diagnosis of bone metastasis was low, but its positive predictive value was high and superior to that of total ALP. PMID- 1458598 TI - Interference of maltose in Lana AG kit determination of 1,5-anhydroglucitol and how to avoid it. PMID- 1458599 TI - Effect of gastric lipase on turbidimetric and dry-film methods for measuring pancreatic lipase. PMID- 1458600 TI - Interference of Tienam in colorimetric determination of 5-aminolevulinic acid and porphobilinogen in serum and urine. PMID- 1458601 TI - Influence of dilution medium on measurements of indocyanine green concentration. PMID- 1458602 TI - Simple qualitative immunoassay of human anti-mouse antibodies evaluated. PMID- 1458603 TI - Unavailability of drug metabolite reference material to evaluate false-positive results for monoclonal EMIT-d.a.u. assay of amphetamine. PMID- 1458604 TI - Effects of ionic strength on determinations of alkaline phosphatase isoenzymes. PMID- 1458605 TI - AIDS testing expands. PMID- 1458606 TI - Flow cytometry in the clinical laboratory. Principles, applications and problems. PMID- 1458607 TI - Quantities and units for metabolic processes as a function of time. Recommendations 1992. PMID- 1458608 TI - Bone metal content in patients with chronic renal failure. AB - Bone accumulation of metals, other than aluminum (Al), in patients with chronic renal failure (CRF) has rarely been studied. We report the bone and blood levels of iron (Fe), vanadium (V), lead (Pb), Al and calcium (Ca) in 18 CRF patients on long-term hemodialysis and in 14 controls (C). Significant increments in mean blood Al (1,300%), V (160%) and Fe (60%) and decrease in blood Pb (-50%) were found in the patients with CRF. Renal subjects had higher bone concentrations (mean +/- S.E.M.; microgram/g of bone) of Al (CRF = 129.1 +/- 16.9; C = 12.6 +/- 2.9; P < 0.0001), Fe (CRF = 940.4 +/- 133.4; C = 263.4 +/- 49.0; P < 0.0001) and V (CRF = 2.55 +/- 0.43; C = 1.39 +/- 0.36; P = 0.0308) and lower Ca (CRF = 268.2 +/- 11.1 mg/g; C = 377.2 +/- 28.1; P = 0.0017). A positive correlation was found between bone Al and V (r = 0.355, P < 0.05). Results indicated that a significant bone accumulation of Al, Fe and V, but not Pb, occurred in the hemodialyzed azotemic individuals. PMID- 1458609 TI - High-performance liquid chromatographic assay for L-glyceric acid in body fluids. Application in primary hyperoxaluria type 2. AB - We describe a liquid chromatographic technique to determine L-glycerate in body fluids. The method is based on the derivatisation of the L-glycerate by incubation with lactate dehydrogenase and nicotinamide-adenine dinucleotide in the presence of phenylhydrazine. Oxidation of L-glycerate forms beta hydroxypyruvate which is converted in turn into the related phenylhydrazone. The UV-absorbing derivative is determined using reversed-phase high performance liquid chromatography. The sensitivity was 5 mumol/l and 50 microliters of sample were required. The imprecision relative standard deviation was 4.5% and the recovery was 96.5 +/- 6.8% for L-glycerate in plasma. L-Glycerate concentrations in urine and plasma were less than 5 mumol/l in both normal individuals and patients with glycolic aciduria. In a patient with systemic oxalosis and normal plasma glycolate, plasma L-glyceric acid was 887 mumol/l. PMID- 1458610 TI - Red blood cells and platelet membrane fatty acids in non-dialyzed and dialyzed uremics. AB - Three groups of patients with chronic renal failure (CRF), 16 non-dialyzed, 16 undergoing haemodialysis (HD), 16 undergoing continuous ambulatory peritoneal dialysis (CAPD), and 48 controls were examined. We analyzed the fatty acid composition in membranes from erythrocytes and platelets and the platelet malondialdehyde (MDA) production as an index of thromboxane metabolism. Marked differences in erythrocytes fatty acid composition were observed between patients with CRF and controls and, particularly, among the three groups of patients with CRF. Patients on CAPD were characterized by an increase in oleic acid, while haemodialyzed had a marked increase in arachidonic acid. Platelet fatty acid composition showed similar differences, suggesting a 'systemic' membrane abnormality. Platelet MDA was increased in haemodialyzed and positively correlated with the platelet arachidonate content. PMID- 1458611 TI - Distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and HDL subfractions of untrained and trained normolipemic men. AB - The distribution of lipoprotein species (LpA-I, LpA-I:A-II) in serum and within HDL subfractions (HDL2b, HDL2a, HDL3) was examined in 26 sedentary and 19 endurance trained normolipemic male individuals. The concentrations of lipids and apolipoproteins in serum and HDL subfractions and the concentrations of LpA-I and LpA-I:A-II were determined. Significant differences (Mann-Whitney-U-test) were found in serum concentrations of apoB (P < 0.05), apoA-II (P < 0.01) and LpA-I:A II (P < 0.001). In HDL3 apoA-II concentration was significantly lower in the trained group (P < 0.05) but in HDL2 subclasses the concentrations of apoA-I and apoA-II did not differ between the groups. Despite similar concentrations of the two apolipoproteins, there were difference in the distribution of lipoprotein species within HDL2 subfractions. The concentrations of LpA-I did not differ, but the concentrations of LpA-I:A-II particles were higher in the trained group. Untrained and trained had similar concentrations of apoA-II (in HDL2b) but obviously more apoA-II containing particles and this leads to the assumption that within HDL2 of endurance trained individuals LpA-I:A-II particles have a lower apoA-II content compared with particles of untrained individuals. The data emphasize, that normolipemic individuals of different maximum oxygen uptake have a different distribution and composition of lipoprotein species (LpA-I, LpA-I:A II). PMID- 1458612 TI - A screening method for cystine and homocystine in urine. PMID- 1458613 TI - Selenium in Graves' disease. PMID- 1458614 TI - Standardization of Lp(a) assays. PMID- 1458615 TI - Incidence of 'unsuspected' extranodal head and neck lymphoma. AB - A series of 100 consecutive patients presenting with non-Hodgkin's lymphoma in the head and neck region was reviewed. An examination of the contribution made to the staging classification by an otolaryngological examination showed that one third of patients presenting with cervical nodes had unsuspected extranodal disease in Waldeyer's ring. Overall 14% of patients undergoing an otolaryngological examination had their disease upstaged because of that examination. PMID- 1458616 TI - Changes in immunologic response in tonsillectomized children. I. Immunosuppression in recurrent tonsillitis. AB - The possible immunoregulatory role of the tonsils was studied by determining immunoglobulins IgG, A, M, E and factors C'3, C'4 and PFB of the complement system before and after tonsillectomy. The synthesis in vitro of IgG and IgM by lymphocytes stimulated with pokeweed mitogen was also measured. There were statistically significant differences between pre and post-operative levels of serum IgG, IgA and IgM, which decreased after surgery. Practically no change in the mean values of IgE and no significant differences in the levels of serum C'3, C'4, and PFB, were found. The in-vitro synthesis of both immunoglobulins (IgG, IgM) by lymphocytes increased significantly after tonsillectomy. Our results suggest that not only does tonsillectomy have no counterproductive effect on the immune system, but that, on the contrary, it seems to improve the immune response, since it appears to unblock the suppression to which the immune system was subject. PMID- 1458617 TI - Changes in immunological response in tonsillectomized children. II. Decreased cellular response. AB - The immunological cellular response was studied in 22 children aged between 5 and 10 years. One week before and one month after tonsillectomy, the mitogenic response to phytohaemagglutinin (PHA), concanavalin (ConA) and pokeweed mitogen (PWM) was tested. Our results showed statistically significant decreases in stimulation index (SI) to PHA, ConA and PWM after tonsillectomy. This suggests that the tonsils may influence the cellular immune status in children. The higher level of preoperative activity in children with recurrent tonsillitis could be understood as the result of stimulation of lymphocytes by bacteria. PMID- 1458618 TI - The role of mucosal receptors in the nasal sensation of airflow. AB - 50 subjects were admitted into a randomized double-blind placebo controlled cross over trial with 4% lignocaine as the active drug and normal saline as the placebo. Each subject had 2 ml of solution sprayed into each nasal cavity and all subjects had both sprays but on different occasions. The order in which the sprays were administered was randomized. The subjective sensation of nasal airflow was measured using a visual analogue scale before and after the spray. These measurements were made under conditions of the same airflow rate, which was monitored throughout the experiment using a reprogrammed NR6 rhinomanometer. Objective nasal patency was measured as peak nasal inspiratory flow rate. It was found that the nasal sensation of airflow decreased slightly after both lignocaine (difference between medians 5.0; 95% confidence interval -2.91 to 6.11) and normal saline (difference between medians 6.0; 95% confidence interval 1.02 to 7.21). Nonparametric analysis of variance showed this difference to be non-significant (P = 0.73). In addition there was no significant change in objective nasal patency. The results suggest that nerve endings in the nasal mucosa play no part in sensing nasal airflow during respiration. PMID- 1458619 TI - Nasal airflow receptors: the relative importance of temperature and tactile stimulation. AB - The receptors responsible for the nasal sensation of airflow have not been identified with certainty. Although both mechanoreceptors and thermoreceptors have been implicated, evidence suggests that the nose is more sensitive to cold air than to air at body temperature. The present study was designed to investigate the relationship between the velocity and the temperature of an airjet as regards its ability to stimulate the nasal lining. Both the nasal vestibule and the nasal cavum are more sensitive to cold air than to air at mean intranasal temperature (P < 0.001). A similar effect is seen with warm air which is as stimulating as cold air. The nasal vestibule is twice as sensitive as the nasal cavum to an airjet at mean intranasal temperature (P < 0.001). It is concluded that the nasal vestible is very sensitive to the tactile stimulation of an airjet. This effect is highly temperature dependent being much more pronounced for air temperatures above or below the mean intranasal temperature. The temperature effect is relatively more important in the nasal cavum which is very much less sensitive to stimulation than the vestibule. PMID- 1458620 TI - T3 laryngeal cancer: a retrospective study of the Dutch Head and Neck Oncology Cooperative Group: study design and general results. AB - 511 Patients with T3 N0-3 M0 squamous cell carcinoma of the larynx, treated in the Netherlands from 1975 until 1984, were retrospectively analysed. Four different treatment policies were followed: primary surgery, planned combination of radiotherapy and surgery, primary radical radiotherapy, and selective radiotherapy. General results are presented. Local control rate was 72%. Regional control rate was 90% for clinically N0 patients and 78% for clinically N+ patients. Salvage therapy was overall successful in 38%. Surgical salvage for local radiation failures (with regional relapse) was successful in 69%, and for regional failures (without local relapse) in 46%. Ultimate locoregional control was 78% and, due to 8% distant metastases, 5-year actuarial corrected survival was 70%. Prognosis did not improve over the years. Corrected survival was independently correlated with tumour extension, involvement of neck nodes and treatment strategy. Corrected survival was similar for primary radiotherapy and primary surgery, but significantly better for planned combined therapy. Multiple primary tumours occurred significantly more often in male (19.5%) than in female patients (7.3%) (P = 0.05), the bronchus being most commonly affected. Cumulative actuarial risk for metachronous tumour was 15% after 5 years and 30% after 10 years so prevention and early detection of these second tumours may play the most important role in improving overall survival rates in the future. PMID- 1458621 TI - The role of calcium alginate swabs in adenotonsillectomy. AB - A randomized controlled study using swabs of calcium alginate versus gauze was undertaken to evaluate the haemostatic capabilities and the shortening of operative time. Haemostasis in adenoidectomy was shown to be more effective and the operating time shortened (P = 0.05) by the use of calcium alginate. Haemostasis and operating time for tonsillectomy were not affected. PMID- 1458622 TI - Non-surgical management of acoustic neuromas. AB - Watchful waiting is one of the options available in the management of acoustic neuromas and this article deals with 13 patients who were so managed. Non operative management was advised because of age, poor general health, small size of tumour, only hearing ear, or in patients unwilling to undergo surgery for various reasons. This group was followed up at 6-12-monthly intervals and the follow-up period ranged from 1 to 18 years (mean 5.3 years). Ten patients had small tumours and only in 2 of these was increase in tumour size demonstrated on follow-up CT scan. In one this increase was later followed by regression. Two patients required partial removal of tumour because of increasing symptoms after 3 and 7 years of follow-up; one of them died on the twelfth post-operative day. There appears to be a small group of patients for whom delay is worth while rather than to subject all patients with acoustic neuroma to surgery from which full recovery cannot be guaranteed. PMID- 1458623 TI - The effect of parental smoking on outcome after treatment for glue ear in children. AB - A sample of 201 children aged between 2 and 9 years with bilateral chronic otitis media with effusion (OME) were treated prospectively and at random by adenoidectomy, adenotonsillectomy, or with neither procedure. In all cases only a unilateral grommet was inserted and the contralateral unoperated ear was examined one year post-operatively for persistence or resolution of the effusion. A self administered questionnaire was completed by the parents concerning their smoking habits. The resolution of effusion following surgery was assessed in relation to smoking by by the mother and father separately and in combination. Clearance of glue was statistically less frequent where the child's mother or where both parents smoked. This was related to the number of cigarettes smoked by the mother or both parents. The adverse effect was demonstrable whether or not adenoidectomy or adenotonsillectomy had been performed for treatment. The findings lend further support or professional and governmental opinions of a deleterious effect of passive smoke exposure on children and in this case parental smoking has been shown to have an adverse effect on the outcome of OME following surgical treatment. PMID- 1458624 TI - Results of full-thickness laryngotracheal wall reconstruction: a survey of the literature. AB - Full-thickness reconstruction of the laryngotracheal wall is needed after tumour removal, and also in patients where lumen augmentation is required to resolve laryngotracheal stenosis. For repairing such defects, several techniques are available. All techniques are more successful when small defects are reconstructed and less successful when there is a major deficit. The main problem with most methods of reconstruction is their unreliable blood supply which becomes most obvious in repairing larger areas. PMID- 1458625 TI - Computed tomography (CT) and magnetic resonance imaging (MRI) in T-stage evaluation of oral and oropharyngeal carcinomas. AB - 174 CT and 32 MRI investigations were carried out on patients with carcinomas of the mouth and oropharynx. The methods were compared and their value in predicting the pre-therapeutic T-staging studied. The combination of CT and clinical examination was able to improve the T-staging considerably compared with clinical examination alone. MRI was superior to CT in delineating the tumour margins in 78% of patients. T1-weighted and gradient echo sequences after intravenous gadolinium injection were particularly useful. Nevertheless, T-staging based on clinical and CT-findings was changed in only 5% of patients by MRI. MRI is especially useful in T1 tumours and in cancer of the base of the tongue. MRI should also be used instead of CT were dental fillings obscure the region of interest. If there are good MRI facilities and an experienced team available MRI can be used before CT. PMID- 1458626 TI - CO2-laser treatment of recurrent glottic carcinoma. AB - The records of 23 patients treated by CO2-laser surgery for recurrent glottic carcinoma after radiotherapy were studied retrospectively to assess treatment results and complications. 15 patients (65%) were cured with one or more laser procedures. The remaining 8 underwent a total laryngectomy for a second or third recurrence. One patient (4%) died of disease. No major complications from CO2 laser surgery were encountered. It is concluded that CO2-laser surgery is a safe method of treatment of recurrent glottic carcinoma. PMID- 1458627 TI - Treatment of T3 carcinoma of the larynx by surgery or radiotherapy. AB - T3 carcinoma of the larynx may be treated by surgery or by irradiation. A large number of oncologists feel that radical surgery offers a better chance of cure than does radiotherapy. We report a series of 147 patients with T3 N0 carcinoma of the larynx treated either by irradiation with salvage laryngectomy in the event of a recurrence, or by total laryngectomy. 109 patients had radiotherapy and 38 patients underwent surgery. The groups were well matched with no significant difference between the significant prognostic factors. The 5-year survival rate between the radiotherapy (70%) and surgery (40%) groups was significantly different (chi 2 = 4.48, d.f. = 1, P < 0.05). In spite of the well known problems associated with retrospective studies the present series suggests that radiotherapy combined with salvage surgery is an oncologically sound option for treating T3 laryngeal carcinoma. PMID- 1458628 TI - The use of ventilation tubes and the incidence of cholesteatoma surgery in the paediatric population of Liverpool. AB - Many surgeons believe that grommet insertion has reduced the incidence of cholesteatoma and thus radical mastoidectomy. Several causes for this trend have been postulated, including the increased use of ventilation tubes to treat otitis media with effusion. We have studied the number of operations for cholesteatoma, together with the number of ventilation tube insertions in the paediatric population of Liverpool, over a 28-year period between 1963 and 1990. There was a decline in the number of operations for cholesteatoma and an increase in the use of ventilation tubes, but there was no significant correlation between the two. This suggests that other factors are responsible for the decline in surgery for cholesteatoma. PMID- 1458629 TI - The quantitative analysis of dysphonia. AB - A clinical method of measuring 'hoarseness' is presented. Its value is assessed in 3 different types of vocal cord lesion and compared against normal values. There are shown to be significant differences between the normal and the abnormal voice and also differences between each type of vocal cord lesion. We feel that this quantification of hoarseness is useful in the treatment of patients as well as in monitoring their progress under therapy. PMID- 1458630 TI - Cell kinetics in squamous cell carcinoma of the head and neck. PMID- 1458631 TI - Salvage laryngectomy after radical radiotherapy for laryngeal carcinoma. AB - Of 376 patients who were treated by radical radiotherapy for squamous carcinoma of the larynx, 56 subsequently underwent total laryngectomy. Residual or recurrent tumour was identified in 43 of the resection specimens, and necrosis alone in 13 cases, although a positive biopsy had been obtained in 3 of these prior to salvage laryngectomy. No disease related factors such as site or stage of the original tumour, or treatment related factors such as radiation type or dose, were found to be predictive of whether or not tumour was present. The clinical opinion of an experienced surgeon was found to have a positive predictive value of 0.86 for the presence of tumour. The fistula rate of salvage laryngectomy, 15 out of 56, was similar to that of other series. The actuarial cause specific 5-year survival for patients with tumour was 0.589, and for patients with necrosis only was 0.923. Intercurrent, smoking related disease was the cause of death in 16 of the 33 patients who have died. PMID- 1458632 TI - What is pseudopelade? PMID- 1458633 TI - Fundamentals of skin cancer/melanoma screening campaigns. AB - There is increased world-wide concern about the rising incidence of melanoma and non-melanoma skin cancer. Screening theoretically reduces death and morbidity from skin cancer/melanoma. Visual examination of the skin is a rapid, safe and inexpensive screening tool. In this review the fundamentals of early disease detection before implementation of a public-health screening programme are critically analysed with reference to the skin cancer/melanoma, epidemic. It is concluded that skin cancer/melanoma fulfils, for the most part, the criteria enunciated by Wilson and Jungner in 1968. However, information about the effect of screening on reducing incidence and mortality is still lacking. Future research should focus on methods of improving compliance and on the costs and benefits of such screening programmes. PMID- 1458634 TI - The application of the seven-point check-list in the assessment of benign pigmented lesions. AB - One hundred consecutive histologically benign lesions seen at a pigmented lesion clinic were studied prospectively to assess the diagnostic accuracy of the seven point check-list. Lesions were scored by both patient and physician. Thirty per cent of lesions attained a suspicious score. While there was a high level of agreement between patient and clinician regarding the individual characteristics of a lesion as defined in the check-list, final assessments differed. Most patients considered their lesions suspicious, whereas the clinicians correctly recognized that in 94% cases they were benign. The seven-point check-list often fails to exclude common benign pigmented lesions. The revised (1989) check-list is even less specific (70% of lesions achieving a suspicious score). Such check lists are difficult for the inexperienced to interpret. Clinical familiarity is required in order to provide a confident diagnosis. Future emphasis should be directed towards improving screening in primary care. PMID- 1458635 TI - Cutaneous metastases from breast carcinoma: a report of 18 cases. AB - In this study, the authors report 18 patients with metastatic breast carcinoma affecting the skin, observed since 1988 in Forli, Italy. The results are compared with those already published in the literature. PMID- 1458636 TI - Skin thickness in psoriasis. AB - Skin thickness measured by the Harpenden skin-fold caliper showed that the uninvolved or non-lesional skin thickness in psoriasis does not differ significantly from that of normal skin. It is thinner in females than in males under 65 years and decreases with age in both sexes. It is thinner in those with fair skin compared to those who tan easily. Uninvolved skin thickness in psoriasis appears to influence the thickness of an adjacent psoriatic plaque. PMID- 1458637 TI - Health-care professionals' views of the effectiveness of pressure ulcer treatments. A survey among nursing-home physicians, dermatologists and nursing staff in The Netherlands. AB - In a survey, 237 nursing-home physicians, 113 dermatologists, and 164 supervisory nurses in nursing homes rated 30 treatments for stage III pressure ulcers by scoring their effectiveness. On average, there seems to be a fair degree of consensus between these groups of health-care workers about the effectiveness of most treatments. The most notable exceptions are ultraviolet light, ultrasound, and laser therapy and myocutaneous flap operations. Here, the dermatologists disagree with both nursing-home physicians and nurses. However, within all specialties there is disagreement about the efficacy of ultraviolet light, ultrasound, and laser therapy and the topical application of zinc oxide, betadine iodine, sodium hypochlorite and a few others. PMID- 1458638 TI - Palmoplantar keratoderma of Unna-Thost: response to biotin in one family. PMID- 1458639 TI - Localized crusted scabies in the acquired immunodeficiency syndrome. AB - Crusted scabies (CrS) is an uncommon occurrence among patients with AIDS. Indeed to date only five cases have been described, all with widespread lesions. A case of localized CrS appearing as a yellowish and crusted plaque on the second right toe is reported in a woman with AIDS. Scraping off the verrucous surface, as well as punch-biopsy revealed many mites within the horny layer. The infestation is related to the cutaneous immune response and thus CrS should be considered an opportunistic infestation in AIDS. The importance of the early diagnosis of CrS in order to prevent disseminated lesions and involvement of other health-care workers is underlined. PMID- 1458641 TI - Familial tufted angioma. AB - Tufted angioma is a rare slowly progressive vascular lesion found typically in children and young adults. Cases appear sporadically and clinically have been confused with low grade angiosarcoma, Kaposi's sarcoma, and multiple glomus tumours. We report a case of a patient with tufted angioma in whom a strong family history of similar lesions is apparent, transmitted in an autosomal dominant mode of inheritance. PMID- 1458640 TI - The use of calcipotriol in HIV-related psoriasis. AB - We report the case of a 28-year-old homosexual man with advanced HIV disease (CDC classification group IV A) who developed erythrodermic psoriasis which responded to calcipotriol, a topical vitamin D analogue. We believe this to be the first reported case of HIV-related psoriasis responsive to this form of treatment. Systemic therapy for HIV-related psoriasis is limited because of immunosuppressive effects. We suggest that calcipotriol may prove to be a useful therapeutic option in these patients. PMID- 1458642 TI - Lichen planus follicularis tumidus with cysts and comedones. AB - The lichen planus follicularis tumidus was described by Belaich et al. in 1977, and we have found 13 cases published so far. We report two cases we have recently seen, one of them with multiple lesions on the head, and the other with a temporo frontal lesion. PMID- 1458643 TI - Localized familial redundant scalp: atypical cutis verticis gyrata? AB - Two patients, a mother and son, with a conspicuous redundant unique scalp fold are reported. No underlying disorder was found. Light microscopy was unremarkable. An atypical familial form of cutis verticis gyrata is suggested. PMID- 1458644 TI - Familial acne fulminans. AB - We report a patient of acne fulminans with arthralgia whose sister presented with the same disease at an identical age 10 years earlier. The two affected siblings in our family also had identical HLA phenotypes which further supported the role of genetic susceptibility in acne fulminans. PMID- 1458645 TI - Bullous and haemorrhagic lichen sclerosus with scalp involvement. AB - We describe a patient who developed a generalized blistering eruption due to lichen sclerosus and who was observed to have scalp involvement. Both are unusual manifestations of this disease which merit consideration. Lichen sclerosus is an uncommon disease that most frequently affects the external genitalia of perimenopausal women. The aetiology is unknown. Approximately 20% of affected patients have extragenital lesions that present as small, ivory, shiny round macules or papules that later become atrophic; extragenital lesions are generally asymptomatic. Bullous and haemorrhagic forms may occur but these are generally localized and reports of extensive or generalized involvement are rare. We describe an elderly woman with generalized bullous lichen sclerosus. As an incidental finding, she was observed to have lichen sclerosus affecting her scalp. This has rarely been described and it would appear that she is the third reported case of scalp involvement. PMID- 1458646 TI - Possible induction of malignant melanoma by sunbed use. AB - Malignant melanoma of the female genitalia is rare. A patient who regularly used a sunbed developed a malignant melanoma after 4 years. The possible aetiological role of sunbeds in the development of such a malignancy is discussed. PMID- 1458647 TI - Perianal basal cell carcinoma. AB - Perianal basal cell carcinoma (BCC) is a rare tumour and only a few case reports can be found in the literature. In this location, it is important to differentiate a BCC from a basaloid cloacogenic carcinoma, as the first is an invasive but localized tumour, while the second has a high capacity for metastasis. PMID- 1458648 TI - Epidermolysis bullosa acquisita presenting with localized facial blisters. AB - A 44-year-old woman presented with blisters on her face of 1-month's duration. A biopsy showed a subepidermal bulla with a dermal infiltrate of inflammatory cells and thick linear deposits of immunoreactants along the dermo-epidermal junction. Using Western immunoblots, the patient's IgG antibody was found to recognize type VII procollagen. Moderate doses of oral prednisolone resulted in a complete remission, without a recurrence for more than 3 years. PMID- 1458649 TI - Malignant melanoma complicated by schwannoma. AB - We report two cases of malignant melanoma associated with a schwannoma. Case 1 is a 32-year-old Japanese man who had a nodular melanoma in his epigastrium, associated with one subcutaneous nodule on the neck and another on the right thigh, both of which were histologically-proven schwannomas. Case 2 is a 48-year old Japanese woman with an acral lentiginous melanoma on her right sole who later developed a schwannoma of the cerebello-pontine angle. Of all 146 malignant melanoma cases found in our clinic during the past 20 years, 1.4% were associated with a neurogenic tumour, a significant association. PMID- 1458650 TI - The development of scar sarcoidosis at the site of desensitization injections. AB - Tender nodules may develop at the site of injection of allergen extracts. Some cases can be related to the aluminium contained in the preparation. We report a case where scar sarcoidosis developed at the site of desensitization injections. At presentation, there were no other cutaneous signs of sarcoidosis; systemic signs only developed 2 years later. We suggest that sarcoidosis be considered as a cause of granulomata developing at sites of desensitizing injections, particularly when aluminium is not involved. PMID- 1458651 TI - Generalized morphoea and primary biliary cirrhosis: a rare association and improvement with oxypentifylline. PMID- 1458652 TI - Hypopigmented mycosis fungoides. AB - We report the case of a 25-year-old Jamaican woman with hypopigmented mycosis fungoides. She first developed a hypopigmented patch on her arm at the age of 11 years. Further lesions developed on the trunk and limbs over a period of 10 years. The lesions were completely impalpable. Skin biopsy showed an infiltrate of atypical lymphocytes, some with cerebriform nuclei, suggesting a diagnosis of mycosis fungoides. The lesions cleared with PUVA therapy. PMID- 1458653 TI - Acrodermatitis continua responding to cyclosporin therapy. AB - A 69-year-old man with painful, recalcitrant, localized acrodermatitis continua developed widespread pustulation which was resistant to high-dose methotrexate therapy. Low-dose cyclosporin induced a rapid and persistent remission. PMID- 1458654 TI - Secondary T-cell lymphoma presenting as a giant ulcer. AB - Secondary cutaneous T-cell lymphoma may present with various types of skin lesions, but rarely produces ulceration in contrast to primary cutaneous T-cell lymphoma. We report a case of malignant lymphoma of the tonsil that recurred as a giant cutaneous ulcer on the back of a 45-year-old man. Biopsy of the ulcer revealed a malignant lymphoma of diffuse, mixed-cell type. Surface marker analysis of the tumour cells showed suppressor/cytotoxic T-cell characteristics. The skin lesions were treated by electron beam therapy. PMID- 1458655 TI - Induction of dysplastic-dystrophic anagen-hair-root condition. PMID- 1458656 TI - Semicircular lipoatrophy. PMID- 1458657 TI - Morphological changes associated with growth inhibition of Trichophyton mentagrophytes by amorolfine. AB - Amorolfine inhibited the in-vitro growth of Trichophyton mentagrophytes to some extent at a low drug concentration of 0.8 ng/ml. Corresponding to the growth inhibition, SEM studies revealed a slight modification of hyphal morphology, i.e. a waving of the hyphal surface. These morphological alterations were more extensive with increases in drug concentration and treatment period: collapsed and distorted hyphae and exfoliation of the surface of T. mentagrophytes occurred at 8 ng/ml and marked deformation and disruption of the hyphal structure at 80 ng/ml of amorolfine. TEM revealed thickening of the cell walls and the accumulation of electron-dense granular structures in both the wall and cytoplasm in thin-sectioned cells pretreated with 8 ng/ml or more of amorolfine, although the nuclear and mitochondrial architecture was not noticeably influenced. Cytoplasmic membranes and other membranous structures of organelles such as nuclei and mitochondria were disrupted or fused, thereby losing their essential physiological activity in hyphal cells pretreated with 80 ng/ml of amorolfine. The ultrastructural study thus supports the observation that morphological changes of T. mentagrophytes caused by amorolfine were associated with its growth inhibitory and killing activity, which depended on the drug concentration and treatment time. PMID- 1458658 TI - Influence of amorolfine on the morphology of Candida albicans and Trichophyton mentagrophytes. AB - Amorolfine applied in concentrations of 0.1-100 micrograms/ml causes considerable damage to the ultrastructure of Candida albicans and Trichophyton mentagrophytes: electron-lucent areas appear in the cytoplasm; extracytoplasmic membrane vesicles are formed and deposited in the cell wall; starved fungal cells, with normal ultrastructure, can be found; lysed, dead cells demonstrate the process of severe ultrastructural damage; T. mentagrophytes cell walls especially increase in thickness. The extent of the damage caused by amorolfine is comparable to that produced by azole antifungals. PMID- 1458659 TI - Treatment of dermatomycoses and onychomycoses--state of the art. AB - We have reached a stage whereby many of the superficial mycoses are treatable with short courses of antifungal drugs. However, the minimum duration of therapy has still not been well defined and there remain some mycoses which do not respond to conventional therapy. It may be possible to introduce more radical approaches to therapy such as the single-dose oral or topical therapy for tinea pedis or short-duration therapy for onychomycosis. Amongst these options, topical therapies still have a part to play in the management of onychomycosis, and the role of amorolfine in this respect is of potential value. The ability of the drug to produce lasting remissions after short courses of treatment is also of great interest. Last, but not least, amorolfine has an in-vitro spectrum of activity which covers some of the less common cutaneous pathogens, and hence it may prove of benefit in those infections for which treatment at present is limited. PMID- 1458660 TI - Loceryl nail lacquer--realization of a new galenical approach to onychomycosis therapy. AB - Loceryl nail lacquer was developed to provide the effective antifungal drug, amorolfine, in a once-weekly dosage regimen combined with a convenient mode of application. Traditional formulations such as creams and nail solutions do not fulfil these requirements because they are wiped or washed off very rapidly. Amorolfine nail lacquer builds a non-water-soluble film on the nail plate, and this film remains in place for 1 week. The film contains a high concentration of amorolfine and forms a depot from which the drug is delivered and which allows the drug to permeate the nail plate. The film-forming polymer and the solvent were optimized for drug release, stability, and convenience of application (drying time, no gloss, transparency). In preclinical development, porcine hoof horn was used as a screening model to differentiate between formulations and dosage strengths with respect to the penetration rate. A high drug concentration of 11.72 micrograms/specimen (10 mm in diameter) was reached in the hoof horn after 6 h, increasing to 39.5 micrograms/specimen within 7 days, the maximum duration of the investigation. The drug concentration achieved was far above its minimum inhibitory concentration. Furthermore, the penetration model clearly indicated that amorolfine crossed the horn barrier and was found in the moistened gauze which simulated the nail bed. After a 7-day penetration period, 1.8% of the applied dose (500 micrograms) was available under the nail. PMID- 1458661 TI - Determination of the subungual antifungal activity of amorolfine after 1 month's treatment in patients with onychomycosis: comparison of two nail lacquer formulations. PMID- 1458662 TI - Percutaneous absorption of amorolfine following a single topical application of an amorolfine cream formulation. AB - In an open-label, parallel-group, randomized study percutaneous absorption of 14C labelled amorolfine incorporated into a cream formulation was assessed in healthy male volunteers (n = 12). A single dose of 0.5 g of the 0.25% cream formulation was applied to 100 cm2 of intact (n = 6) and stripped (n = 6) skin for 24 h using occlusive dressing. The remaining drug was removed and the treated skin area of both groups was stripped with adhesive tape. Total urine and faeces were collected in portions up to 3 weeks after the experiment and blood samples were taken at intervals for 3 weeks. Radioactivity was measured in the skin strippings and in the urine, faeces and plasma samples. The intact drug was assessed in the plasma samples. Using mass balance techniques it could be shown that a mean of 92% (range: 84-101%) of the applied radioactivity could be recovered. Small differences in the absorption and elimination of the radioactivity were observed between the two groups but they were not statistically significant (alpha = 0.05). Therefore data from the two groups were pooled. Elimination of drug and drug-related material from the body was very slow. During the 3-week collection period, a mean of 7% (range: 3.8-10.2%) of the dose was excreted in urine and faeces. Another 0.9-3.3% of the dose was retained in the upper layers of the skin as shown by the skin strippings after treatment. Levels of radioactivity and of intact drug in plasma were below the detection limit of 0.5 ng-equiv./ml, respectively. Present data suggest that mean percutaneous absorption of amorolfine following topical application of the 0.25% cream formulation should not exceed 8-10% of the dose applied. PMID- 1458663 TI - Clinical and mycological diagnostic aspects of onychomycoses and dermatomycoses. PMID- 1458664 TI - Comparative efficacy and safety of amorolfine nail lacquer 2% versus 5% once weekly. AB - Altogether 157 patients with onychomycosis affecting not more than 80% of the surface area of nail with intact lunula and matrix were treated once weekly for up to 6 months with amorolfine nail lacquer (2 or 5%) in a double-blind randomized design. Clinical examinations were carried out before, monthly during, and 1 and 3 months after therapy. Mycological examinations were performed before, 1 and 3 months after therapy. One hundred patients were evaluated. According to the overall assessment by the investigators, which was based on the clinical response and mycological findings, there was cure in 12%, improvement in 55% and failure in 33+ of the 2% group. The corresponding figures in the 5% group were: cure in 38%, improvement in 32% and failure in 30%. The difference in the number of cures was statistically significant in favour of the 5% nail lacquer. The most common pathogens isolated were Trichophyton rubrum in 59% of cases and Trichophyton mentagrophytes in 22%. Three months after the end of the treatment the mycological culture was negative in 55% of the 2% group and in 60% of the 5% group. Both concentrations were well tolerated. Only three patients (2%) experienced mild local adverse events. No systemic side-effects occurred and no patient discontinued treatment due to an adverse event. In conclusion, the 5% nail lacquer was more effective than the 2% nail lacquer when used once weekly for up to 6 months for the treatment of mild to moderate onychomycosis, and both concentrations were well tolerated. PMID- 1458665 TI - Comparative efficacy and safety of amorolfine nail lacquer 5% in onychomycosis, once-weekly versus twice-weekly. AB - Amorolfine is a new topical antifungal of the phenylpropyl morpholine class which is highly active both in vitro and in vivo against yeasts, dermatophytes and moulds responsible for superficial fungal infections. Human pharmacological studies have established that amorolfine has a persistent antifungal effect in the nail bed and in the skin without being systemically absorbed. This has been confirmed by clinical work showing that amorolfine is effective in treating dermatomycoses and onychomycoses when administered as cream or nail lacquer. It is ineffective when given orally for systemic mycoses or bacterial infections in animals. In earlier studies a 5% concentration of amorolfine nail lacquer was found to produce a better cure rate in onychomycosis than a lower concentration of 2%. From data available on the penetration of amorolfine and on the persistence of mycologically relevant tissue concentrations, it appeared likely that once- or twice-weekly application of nail lacquer should suffice to produce a satisfactory therapeutic effect in onychomycosis. The aim of this investigation was to assess the efficacy and tolerability of 5% amorolfine nail lacquer given once versus twice weekly to patients with onychomycosis of finger nails and toe nails. PMID- 1458666 TI - Dose-finding study of amorolfine cream (0.125%, 0.25% and 0.5%) in the treatment of dermatomycoses. AB - A total of 725 patients with mycosis of the skin folds, large areas of the body or feet were entered into this double-blind, dose-finding study. Treatment with 0.125, 0.25 or 0.5% amorolfine cream was randomly allocated to patients. The cream was applied once daily for 4 weeks on average. At screening, in 527 patients evaluated for efficacy, a total of 533 pathogens were isolated: T. rubrum (322), T. mentagrophytes (84), E. floccosum (45), M. canis (42), other dermatophytes (14), C. albicans (24) and other yeasts (2). One week after the end of treatment, the culture was negative in 80.5, 81.3 and 84.8% of patients treated with 0.125, 0.25 or 0.5% amorolfine cream, respectively. The differences were not statistically significant. Forty-four out of 714 patients evaluated for safety had local adverse events: 14 (5.8%), 13 (5.5%) and 17 (7.1%) in the amorolfine cream 0.125, 0.25 and 0.5% groups, respectively. Due to local adverse events, six patients (2.5%) in the 0.125% group, six patients (2.6%) in the 0.25% group and seven patients (2.9%) in the 0.5% group discontinued the trial treatment. The most common adverse events were burning, itching, erythema and scaling. No systemic adverse events were reported. PMID- 1458668 TI - Clinical manifestations of onychomycosis. PMID- 1458667 TI - Double-blind comparison of amorolfine and bifonazole in the treatment of dermatomycoses. AB - A total of 232 patients with mycoses of skin folds, body, or feet were entered into a double-blind, parallel group-study. Therapy with 0.125, 0.25, 0.5% amorolfine cream or 1% bifonazole cream was randomly allocated to patients. The cream was applied once daily for 4 weeks on average. At screening, in 208 patients evaluated for efficacy, a total of 225 fungi were isolated: T. rubrum (77), T. mentagrophytes (65), other dermatophytes (15), C. albicans (34), other yeasts (26) and moulds (8). One to three weeks after ending therapy, the percentage of patients with negative cultures were as follows: 87.3, 91.7, 90.7 and 92.2% in the amorolfine cream 0.125%, 0.25%, 0.5% and bifonazole cream 1% groups respectively. The differences were not statistically significant. Six out of 223 patients evaluated for safety had local adverse events: one (1.7%), two (3.6%) and three (5.4%) in the amorolfine cream 0.125%, 0.25% and bifonazole cream 1% groups respectively. The most common local adverse events were burning and increased itching, erythema or weeping. A once-daily application of amorolfine cream can be recommended for the treatment of dermatomycoses on the basis of the results from this study. However, a further and similar study with a larger number of patients was required to select the concentration of amorolfine cream for therapeutic use. PMID- 1458669 TI - Amorolfine in the treatment of onychomycoses and dermatomycoses (an overview). PMID- 1458670 TI - Preclinical data and mode of action of amorolfine. PMID- 1458671 TI - CD8 T lymphocyte subset markers and HIV infection. PMID- 1458672 TI - Intravenous immunoglobulin in the treatment of paediatric cerebral malaria. AB - Hyperimmune globulin can inhibit and reverse the cytoadherence between Plasmodium falciparum-infected erythrocytes and melanoma cells in vitro. Cytoadherence is believed to mediate disease in cerebral malaria. Therefore we studied the efficacy of i.v. immunoglobulin, purified from the plasma of local semi-immune blood donors, as an adjunct to standard treatment for cerebral malaria in Malawian children. The immunoglobulin preparation (IFAT antimalarial antibody titre 1:5120) recognized erythrocyte-associated antigens of each of 22 Malawian P. falciparum isolates studied, and reversed binding of Malawian isolates to melanoma cells. Immunoglobulin did not reverse binding to human monocytes or to cells of the human histiocytic lymphoma cell line U937. Thirty-one children with P. falciparum parasitaemia and unrousable coma were enrolled. All were treated with i.v. quinine dihydrochloride; in addition patients were randomized to receive either immunoglobulin (400 mg/kg by i.v. infusion over 3 h) or placebo (albumen and sucrose by similar infusion) in a double blind trial with sequential analysis. Of 16 patients receiving immunoglobulin, five (31%) died and five survivors had neurological sequelae. Of 15 patients receiving placebo, one (7%) died and two had sequelae. Parasite clearance, fever clearance and coma resolution times in survivors were similar in the two groups. Although the difference in outcome between the two groups was not significant, the trial was stopped because immunoglobulin was demonstrated not to be superior to placebo. PMID- 1458673 TI - Thyroid autoimmunity and hypothyroidism during long-term treatment with recombinant interferon-alpha. AB - Forty-five patients with myeloproliferative or myelodysplastic syndromes, treated with recombinant interferon-alpha (rIFN-alpha) for a minimum of 1 up to 4 years, were examined for the occurrence of thyroid autoimmunity. During treatment, the rate of thyroid autoimmunity rose to more than 20%. The decrease in severity and frequency of thyroid autoimmunity after withdrawal of IFN shows that this is a potentially reversible side effect. The key determinant for the manifestation of this IFN-related autoimmune phenomenon seems to be a predisposition for autoimmunity, since patients with initially detectable thyroid antibodies are prone to exacerbations of thyroid autoimmunity. Concurrent with thyroid autoimmunity, hypothyroidism occurred but did not correlate with the levels of thyroid antibodies, although severe hypothyroidism in two patients was accompanied by increased levels of thyroid antibodies. This investigation shows that thyroid autoimmunity and consecutively hypothyroidism must be expected in certain patients treated with rIFN-alpha during long periods. Furthermore, it may be assumed that IFN-alpha does not induce the development of autoimmunity, but rather enhances the levels of pre-existent thyroid antibodies. PMID- 1458674 TI - The significance of activation markers on CD8 lymphocytes in human immunodeficiency syndrome: staging and prognostic value. AB - The objective of this prospective cohort study was to evaluate the expression of activation markers on CD8 lymphocytes at various clinical stages of HIV infection and to determine the value of these markers in identifying patients likely to have rapidly progressive disease. One hundred and three HIV+ patients, divided into four disease stages, and 34 seronegative controls were evaluated at study entry using flow cytometric immunophenotyping. The HIV patients were followed clinically for disease progression during the following 2 years. CD8 cell numbers and percentage of lymphocytes are increased after HIV infection. Expression of the CD38, HLA-DR and CD57 markers on CD8 cells was significantly increased in asymptomatic HIV-infected patients when compared with controls, as was the CD8 cell population which did not coexpress Leu-8. These activation markers were observed to be further increased in patient groups with more clinically advanced infection. The percentage of CD38 on CD8 cells emerged not only as a discriminator of disease severity, but was a strong predictor of progression in asymptomatic, lymphadenopathy and ARC patients. Given the utility of activation markers on CD8 lymphocytes in staging disease and predicting clinical outcome, the measurement of these parameters should be considered in the monitoring and management of HIV patients. PMID- 1458675 TI - Deficiency of complement component C3 is associated with accelerated removal of soluble 123I-labelled aggregates of IgG from the circulation. AB - Complement and erythrocyte complement receptors CR1 (CD35) play an important role in the clearance of immune complexes. We studied the elimination of soluble 123I labelled aggregates of human immunoglobulin G (123I-AIgG), used as a model for immune complexes, in two patients with a congenital and two patients with an acquired deficiency of complement component C3, and compared these with 10 healthy controls. The first disappearance halflife of 123I-AIgG was shorter (3.3 +/- 0.4 versus 7.0 +/- 0.4 min in the controls, P = 0.005) and maximal hepatic uptake of aggregates was increased in the C3 deficient patients (maximal liver/background ratio 3.6 +/- 0.4 versus 2.7 +/- 0.2 in controls, P = 0.04). Apparently, in the absence of C3, removal of circulating immune complexes by the liver is accelerated, probably through Fc receptor-dependent mechanisms. PMID- 1458676 TI - Kinetics of lymphocyte subsets from peripheral blood during a Plasmodium falciparum malaria attack. AB - Variations of lymphocyte subsets were followed longitudinally in 16 patients during an acute falciparum malaria attack. Before treatment, lymphocyte numbers were highly reduced, but the subset distribution was similar to that of healthy individuals. After parasite clearance, lymphocyte counts were normalized and the subset distribution was unchanged. This led to a normalization of all the absolute counts of lymphocyte subsets, except CD8+. The fast normalization of lymphocyte counts suggests that the initial decrease in lymphocyte numbers may reflect sequestration. Magnitude and kinetics of this variation were not related to parasite density or to severity of the attack. Activated T cells (CD3+HLA-DR+) were fewer in African than in European patients, suggesting the importance of the past exposure to malaria parasites in reallocation phenomena. These variations in lymphocyte numbers must be taken into account in the design and the analysis of cellular investigations in patients experiencing a falciparum malaria attack. PMID- 1458677 TI - Interference of Wegener's granulomatosis autoantibodies with neutrophil Proteinase 3 activity. AB - Classic anti-neutrophil cytoplasmic autoantibodies (C-ANCA) are disease-specific markers of Wegener's granulomatosis (WG). The possible pathogenetic role of these autoantibodies, which are directed against Proteinase 3 (PR3), is not yet clear. We studied the effect of C-ANCA on PR3 proteolytic activity and on the complexation of PR3 with alpha 1-antitrypsin (alpha 1AT). C-ANCA IgG from eight patients with active WG significantly inhibited PR3 proteolytic activity, particularly towards elastin (median 84.2% inhibition). C-ANCA IgG significantly inhibited the complexation of PR3 with alpha 1AT (median 58.8% inhibition). Moreover, addition of purified PR3 to C-ANCA-positive sera from WG patients yielded less complexes with alpha 1AT (median 44.8%) compared with sera containing perinuclear anti-neutrophil cytoplasmic autoantibodies (P-ANCA) or ANCA-negative sera. These findings indicate the existence of a hitherto unknown property of C-ANCA, which may be of importance in the pathogenesis of WG. PMID- 1458678 TI - Autoantibodies against cyclophilin in systemic lupus erythematosus and Lyme disease. AB - Autoantibodies against cyclophilin, a cyclosporin A binding protein, were detected in sera of 29 of 46 (63%) patients with systemic lupus erythematosus and 14 of 40 (35%) Lyme disease patients. The antibodies are directed against the denatured form of both the major and minor isoform of cyclophilin and can be demonstrated in Western blots. Some first-degree relatives of lupus patients also express these antibodies. They are specific for cyclophilin and are not the consequence of hypergammaglobulinaemia. Four monoclonal IgM antibodies from a patient with lepromatous leprosy also bound to cyclophilin. The generation of these antibodies may be of special interest because they are against a protein involved in the control of the immune system not known to be directly associated with DNA or RNA. PMID- 1458679 TI - Immunoglobulin class and IgG subclass distribution of anticardiolipin antibodies in patients with systemic lupus erythematosus and associated disorders. AB - The class and subclass distribution of an antibody response may give insight into the stimulating mechanism and likely effector functions. IgA, IgG and IgM anticardiolipin antibodies (aCL) were quantified in a consecutive series of 200 samples sent to an autoimmune serology laboratory to determine the relationships between aCL responses of each of these antibody classes and, in particular, whether there was any utility in the measurement of IgA aCL. Positive results for one of the three aCL isotypes were found in 105 samples (53%), and in 41 samples IgA aCL was detected (21%). However, amongst these unselected samples, little additional information was obtained by measurement of IgA aCL, which was found in conjunction with IgM or IgG aCL in all but five samples, and in these the isolated elevation of IgA aCL was only slight, and showed no disease specificity. The levels of each of the four IgG subclasses of aCL were measured in a subgroup of serum samples from 28 patients with autoimmune disease and from 29 patients with syphilis. Amongst the SLE patients IgG1 and IgG3 aCL were the predominant IgG subclasses, consistent with an antigen-driven, T cell-dependent antibody response. However, a subgroup of eight of the autoimmune subjects had predominant elevation of IgG2 aCL, possibly implying a role for T cell-independent antibody production to cardiolipin. Amongst the syphilis patients IgG1 and IgG3 aCL were also the predominant subclasses of aCL but IgG4 aCL were also detected in the majority of subjects, consistent with prolonged antigenic stimulation. PMID- 1458680 TI - An altered repertoire of T cell receptor V gene expression by rheumatoid synovial fluid T lymphocytes. AB - The pattern of T cell receptor V gene expression by lymphocytes from rheumatoid synovial fluid and paired peripheral blood samples was compared using a polymerase chain reaction (PCR)-based assay. Eight rheumatoid arthritis (RA) patients who had varying durations of disease (from 2 to 20 years) were studied. In all patients there was evidence of a different pattern of V gene expression between the two compartments. Significantly increased expression of at least one V alpha or V beta gene family by synovial fluid T cells was observed in all the patients studied. Three different V alpha (V alpha 10, 15 and 18) and three V beta (V beta 4, 5 and 13) families were commonly elevated. Sequencing of synovial V beta transcripts demonstrated that the basis of increased expression of selected V gene families in the synovial fluid was due to the presence of dominant clonotypes within those families, which constituted up to 53% of the sequences isolated from one particular synovial V gene family. There were considerable differences in the NDJ sequences found in synovial and peripheral blood T cell receptor (TCR) transcripts of the same V beta gene family. These data suggest that the TCR repertoire in the two compartments differs, and that antigen-driven expansion of particular synovial T cell populations is a component of rheumatoid synovitis, and is present in all stages of the disease. PMID- 1458681 TI - Fibroblast growth factors in connective tissue disease associated interstitial lung disease. AB - Fibrosis is a major cause of morbidity and mortality in chronic inflammatory diseases, especially interstitial pulmonary disorders. Fibroproliferation is an important part of this fibrotic response, and is mediated largely through growth factors such as platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) I and tumour necrosis factor-alpha (TNF-alpha). Although there is some evidence implicating these cytokines in fibrotic disorders, strong evidence in vivo is almost nonexistent. In order to ascertain the role that these factors play in inflammatory lung disorders associated with connective tissue diseases, alveolar mononuclear cells have been obtained from subjects by bronchoalveolar lavage and assessed for the spontaneous release of fibroblast growth factors. The study population consisted of subjects with a variety of different connective tissue disorders, both with and without inflammatory pulmonary complications. It was found that lavage cells spontaneously secreted fibroblast growth factor activity over 24 h with maximum activity detected at 6 to 12 h. Growth factor activity could be detected in most subjects with connective tissue disease associated inflammatory lung disease and some normal subjects, but the amount of growth factor activity was much higher in the former than in the latter. By means of antibody depletion experiments all growth factor activity from lavage cells of normal patients was attributable to TNF-alpha while patients with interstitial lung disease secreted large amounts of PDGF and fibronectin in addition to TNF alpha. Approximately 40-50% of the total released growth factor activity could be accounted for by PDGF, and 100% by the combination of PDGF, TNF-alpha and fibronectin. While TNF-alpha is released from the bronchoalveolar lavage cells of many subjects, in addition, many patients with interstitial lung disease also release spontaneously, large amounts of fibroblast growth factor activity attributable to PDGF and fibronectin. PMID- 1458682 TI - Glomerular immune deposits in murine lupus models may contain histones. AB - Two types of lupus mice, NZB/NZW F1 female hybrids and mice with graft-versus host disease (GVHD), were studied. Histones H3 and H2A were detected by immunofluorescence in glomeruli of 22/22 proteinuric GVHD and 8/12 proteinuric NZB/W F1 female mice; in non-proteinuric animals, 3/5 GVHD and 2/27 NZB/W F1 female were positive. Using antibodies to histone peptides it was shown that mainly the N-terminal regions of histones H3 and H2A were exposed in glomerular deposits. Western blot analysis revealed antibodies to histone subfractions in sera of 33/34 lupus mice that developed proteinuria. This study provides evidence that histones are involved in the pathogenesis of lupus nephritis. PMID- 1458683 TI - Induction of adjuvant arthritis in mice. AB - Adjuvant arthritis, induced by injections of Freund's complete adjuvant into the footpads of some rat strains, has been recognized as a useful animal model for many years. There has, however, been notable lack of success in reproducing this model in other species. We now describe the development of adjuvant arthritis in healthy strain mice approximately 2 months after injection of Freund's complete adjuvant. Although the clinical appearance of the mice and the joint histopathology closely resemble the adjuvant arthritis reported in the rat, we were unable to detect rheumatoid factor in sera from the affected animals. In parallel studies of T cell proliferation, affected animals responded to some mycobacterial antigens but not to the 65-kD heat shock protein of Mycobacterium tuberculosis, suggesting that some other epitope is important in the development of the disease. PMID- 1458684 TI - MRL/lpr-->severe combined immunodeficiency mouse allografts produce autoantibodies, acute graft-versus-host disease or a wasting syndrome depending on the source of cells. AB - MRL/lpr (lpr) mice spontaneously develop a lupus-like illness as well as massive lymphadenopathy. Attempts to transfer autoimmunity by adoptive transfer or radiation bone marrow chimeras have been unsuccessful. Since severe combined immunodeficiency (SCID) mice have been engrafted with human and rat xenografts without apparent graft-versus-host disease (GVHD), we subjected SCID mice to low dose irradiation and reconstituted the mice with spleen cells from young or old lpr mice or with lpr bone marrow. Fourteen out of twenty (70%) of SCID mice engrafted with spleen cells from old lpr mice produced autoantibodies (anti-DNA and anti-Sm) without evidence of the severe lymphoid atrophy previously described for lpr spleen-->+/+ chimeras. SCID mice engrafted with spleen cells from young lpr mice developed acute GVHD and 5/6 (83%) died within 4 weeks post-transfer. Although 8/11 (73%) of lpr-->SCID bone marrow allografts survived for at least 4 months, these mice developed a wasting disease characterized by lymphoid atrophy and fibrosis without the production of autoantibodies. None of the lpr-->SCID grafts resulted in the transfer of double negative T cells or the lymphoproliferative syndrome characteristic of MRL/lpr mice. These findings indicate that SCID mice can be engrafted with splenocytes from old MRL/lpr mice and that B cells continue to secrete autoantibodies for several months in the SCID recipients. This study also demonstrates that, unlike i.p. transplant of xenogeneic cells, acute GVHD is a consistent feature of i.p. transplants of normal allogeneic mononuclear cells into SCID mice. PMID- 1458685 TI - In vitro preactivated human T cells engraft in SCID mice and migrate to murine lymphoid tissues. AB - Mice with severe combined immunodeficiency (SCID) accept grafts of human T and B lymphocytes derived from resting peripheral blood mononuclear cells (PBMC). We wished to determine whether activated human T cells engraft and migrate into lymphoid tissues in SCID mice. PBMC (50 x 10(6)) activated in vitro in a 4-day mixed lymphocyte culture (MLC) were injected into the peritoneum of 12 SCID mice. In 11 of 12 animals killed at 3 or 4 weeks after injection, human cells were detected in cells pooled from lymphoid organs by flow cytometry and by immunohistochemical staining of frozen tissue sections. The percentage of CD45+ cells in the 11 mice ranged from 2% to 45% and the absolute numbers of CD45+ cells recovered from lymphoid organs ranged from 4 x 10(6) to 90 x 10(6). Up to 93% of the human cells expressed the CD3 antigen together with either CD4 or CD8. Human T cells were localized in periarteriolar areas in murine spleens, whereas in the lymph nodes and gut mucosa, the T cells did not show the pattern for T dependent areas found in human lymphoid tissue. Numerous human plasma cells were detected in the spleen and gut mucosal crypts of engrafted SCID mice. Human IgG was detected in the serum of all 11 engrafted SCID mice. The functional activity of human T cells recovered from murine splenic tissue was very low 3-4 weeks after engraftment. PMID- 1458686 TI - Activated T-lymphocytes induce growth inhibition and prostaglandin E2 release from syngeneic glomerular mesangial cells. AB - The concept of an active role of T lymphocytes in the initiation and development of autoimmune glomerulonephritis has gradually evolved from recent investigations. In the present study we started in a murine coculture system to directly examine cellular interactions of intrinsic glomerular mesangial cells (MC) and syngeneic T lymphocytes. Lymph node lymphocytes and, moreover, cloned T helper cells specifically affected syngeneic proliferating MC, causing growth inhibition and prostaglandin E2 (PGE2) release. The T cell specificity of mesangial cell responses was confirmed by demonstrating (i) that MC cocultured with other cell types showed no reaction and (ii) that additional activation of T lymphocytes by IL-2 or concanavalin A significantly enhanced the MC responses. Subsequently, we confirmed the presence of T cell factors in the supernatants responsible for the observed effects: interferon-gamma (IFN-gamma) and tumour necrosis factor (TNF). Experiments with combinations of recombinant mouse IFN gamma and human lymphotoxin or TNF-alpha showed that these lymphokines could substitute for the direct T lymphocyte effects causing a synergistic growth inhibition and PGE2 release from mouse MC. The observed lymphokine activities were not due to mesangiolysis as shown by neutral red uptake of MC. Pointing to the essential role of T helper cell-specific products, IFN-gamma antibodies abolished both the IFN-gamma and the combined IFN-gamma/TNF-alpha effect. Thus, our investigations with syngeneic MC-lymphocyte cocultures demonstrated that cultured MC specifically responded to T lymphocytes and their products. PMID- 1458687 TI - An early defect in primary and secondary T cell responses in asymptomatic cats during acute feline immunodeficiency virus (FIV) infection. AB - As in HIV infection of humans, cats infected with FIV are particularly susceptible to secondary infection by opportunistic pathogens, suggesting an impaired ability to elicit an effective immune response against foreign antigens. In order to investigate the development of immunity in FIV-infected cats, we have used an autologous culture system to directly measure priming of naive CD4+ T cells to soluble protein antigen, in vitro. Using this assay, we showed previously that cats infected with FIV for several months had significantly reduced primary proliferative responses. We have now examined cats before infection, and at varying times after infection with FIV, to determine how soon after infection this defect in T cell priming was evident, compared with other quantitative and qualitative measurements of lymphocyte function. Our results showed a progressive decline in immune function in asymptomatic cats during the acute stage of infection with FIV. Primary T cell responses were most sensitive and a significant reduction in proliferation of naive T cells to foreign antigen occurred 5 weeks after infection, despite normal blastogenesis to T cell mitogens and normal CD4+/CD8+ ratios at these times. Whilst lymphocyte proliferation to T cell mitogens was unaffected throughout, a significant reduction in proliferation to a B cell mitogen occurred from week 8 onwards. CD4+/CD8+ ratios fell significantly from week 13 onwards, and proliferation of the memory T cell population to a recall antigen was significantly impaired later, from week 19 onwards. The defect in the priming of naive T cells to foreign antigen early after infection may be important in determining susceptibility to secondary infections. PMID- 1458688 TI - Gene frequency and partial protein characterization of an allelic variant of mannan binding protein associated with low serum concentrations. AB - Low plasma concentration of mannan binding protein (MBP) has been shown to be the basis for a common opsonic deficiency and suggested to be caused by a single nucleotide substitution at base 230 of exon 1 in the MBP gene. This substitution causes a replacement of glycine (codon GGC) with aspartic acid (codon GAC). Of 123 healthy Danish individuals investigated by polymerase chain reaction performed on exon 1, followed by restriction fragment length polymorphism or allospecific probing, 93 were homozygous (75.6%) for GGC, 28 heterozygous (22.8%), and two homozygous for GAC (1.6%). The gene frequency of the GAC allele was found to be 0.13. DNA sequencing of the cloned exon 1 from one GAC homozygous individual revealed no other substitution. The median MBP concentration in the group containing the GAC allele was 6.4 times lower than in the GGC homozygous group (195 and 1234 micrograms/l respectively). However, the range in plasma concentrations of MBP was wide and overlapping between the groups. MBP protein was detected in both the GAC homozygotes (9 and 387 micrograms/l). Furthermore, no difference in relative mass and biological activity (mannan binding) was found when sera containing the two forms of MBP were investigated. Accordingly, it can be concluded that the GAC allele is able to produce a functional MBP protein which may be detected in serum at low concentrations. PMID- 1458690 TI - Bacterial lipopolysaccharide mediates the loss of CD4 from the surface of purified peripheral blood monocytes. AB - In this study we have looked at the effect of lipopolysaccharide (LPS) on the surface antigen expression of cultured monocytes. Monocytes were purified from peripheral blood mononuclear cells (PBMC) and cultured in the presence or absence of LPS. The cultured cells were then stained with anti-MO3, anti-IL-2R and anti CD4 MoAbs. We have shown that freshly isolated monocytes are IL-2R- and MO3 negative and express CD4 in low density. After overnight culture, without LPS, the expression of these surface markers remained relatively unchanged. However, in the presence of LPS (1 microgram/ml) CD4 expression was reduced to undetectable levels while the expression of IL-2R and MO3 was induced to maximal density. This effect of LPS on monocyte surface antigen expression was demonstrated with LPS preparations from Escherichia coli, Salmonella typhi and Vibrio cholerae. Surface antigen expression after 7 days culture in medium supplemented with non-heat-inactivated serum was essentially as seen after overnight culture, with the exception that LPS-induced IL-2R expression was transient. The ability to prepare monocytes that maintained surface CD4 expression after overnight culture was donor dependent. PMID- 1458691 TI - When do we treat hypercholesterolemia? AB - Although the relationships between elevated total and low-density lipoprotein (LDL) cholesterol and coronary heart disease (CHD) are relatively well established and published treatment guidelines are available, clinicians face a number of complex issues when deciding whom to treat. Specific patient characteristics and potential risk factors, of which less is known, may influence treatment decisions. In this presentation, the current guidelines for treating patients with hypercholesterolemia are reviewed and therapeutic issues that must be considered when selecting patients for treatment are identified. PMID- 1458689 TI - Detection of cytokines at the site of tuberculin-induced delayed-type hypersensitivity in man. AB - Cytokines are chiefly local mediators which play an important role in the regulation of the cell-cell interactions which may be involved in the development of the delayed-type hypersensitivity (DTH) reaction. Using immunohistochemical techniques, the presence of IL-1 alpha, IL-1 beta, IL-6, interferon-gamma (IFN gamma) and tumour necrosis factor-alpha (TNF-alpha) in the skin in tuberculin purified protein derivative (PPD)-induced DTH reactions was investigated in six normal individuals. Cells staining for these cytokines were first observed 6 h after PPD challenge, and they were detected throughout the duration of the 7-day experiment. The number of cells staining for IFN-gamma reached a peak at 48 h, where 33% of the total aggregate cells were positive, but declined thereafter to 3% at day 7. On the other hand, the number of cells staining for TNF-alpha and IL 1 persisted at high levels throughout the observation period of 7 days (e.g. at 48 h and thereafter, about 40% cells positive for TNF-alpha and 20% for IL-1 alpha and IL-1 beta). Double immunofluorescence and staining on sequential sections showed that IFN-gamma-staining cells were CD3+ T cells; TNF-alpha, IL-1 and IL-6 staining cells were mainly of the CD68+ macrophages/monocytes and that 80% of the CD1a+ cells (Langerhans-like cells) in the dermis contained TNF-alpha and IL-1. The presence of these cytokines at the site of inflammation suggests that they may be locally produced by the inflammatory cells. Their persistence during the reaction suggests that they are intimately associated with this response, and are involved in the development of the reaction. PMID- 1458692 TI - Therapeutic intervention for hypercholesterolemia. AB - In previous presentations in these proceedings, the important relationships between cholesterol and coronary heart disease (CHD) have been reviewed. Guidelines, for Europe and the United States, for screening and intervention in persons with elevated total or low-density lipoprotein (LDL) cholesterol have been compared. In this presentation, the current approaches for dietary and drug treatment of hypercholesterolemia are discussed. PMID- 1458693 TI - Cholesterol and cardiovascular disease: how strong is the evidence? AB - The relationship between elevated serum cholesterol and cardiovascular disease, specifically coronary heart disease (CHD), has been and continues to be a source of debate in the medical community. Other issues under debate include criteria for screening for elevated cholesterol, criteria for treatment, and whether intervention to lower elevated cholesterol prior to a cardiac event is cost effective. Most physicians believe this latter statement to be true; however, reports of no decrease in overall mortality rates in those without clinical coronary disease in whom aggressive lowering of cholesterol is achieved may have contributed to the lack of consensus on this most important issue. In this presentation the evidence that links cholesterol and CHD is reviewed and it is demonstrated that lowering elevated cholesterol concentrations can improve quality of life and life expectancy. PMID- 1458694 TI - Treatment of lupus pregnancy: can we reach consensus? PMID- 1458695 TI - Terminal complement complex in synovial tissue from patients affected by rheumatoid arthritis, osteoarthritis and acute joint trauma. AB - The C5b-9 complex (Terminal Complement Complex-TCC) is the final product of the terminal complement pathway. In this study, using the monoclonal antibody MCaE11 (specific for a C9 neoantigen) and an immunohistochemical technique, we examined the TCC deposits in synovial tissues from 4 patients affected by rheumatoid arthritis (RA) and 6 patients affected by osteoarthritis (OA). Synovial tissues from 8 patients affected by acute joint trauma were examined as controls. Furthermore, plasma TCC levels were measured in 44 RA patients and 51 controls, using the above mentioned antibody and a sandwich ELISA. Eight synovial fluids were also included in this study. Abundant TCC deposits were detected in the cytoplasm of the synovial lining cells and of large stromal mononuclear cells in all the RA and in 3 out of 6 OA synovial tissues characterized by histological signs of inflammation. No TCC deposits were found in non-inflamed synovial tissues from patients with joint trauma. In agreement with previous observations, the TCC plasma levels found were significantly higher in RA patients than in controls, but no difference was seen between patients with active and non-active disease. The mean TCC level was significantly higher in the synovial fluid than in the plasma, but no correlation emerged between these two series of values. This study shows that: a) the plasma level of TCCs cannot serve as an indicator of disease activity in RA; b) the TCC deposits in synovial tissue correlate well with the extent of inflammatory synovitis, irrespective of whether the synovitis is rheumatoid or osteoarthritic in nature. PMID- 1458696 TI - Systemic lupus erythematosus and pregnancy: a prospective study. AB - We have prospectively followed 25 pregnancies in 21 patients: 20 were affected by systemic lupus erythematosus (SLE) and 1 by subacute cutaneous lupus erythematosus (SCLE). A flexible treatment schedule was applied to the follow-up of all the pregnancies, and included low dose aspirin, steroids at medium-low dosage and, if needed, azathioprine (AZA) after 20 weeks of gestation. There were 4 spontaneous first trimester abortions and 21 live-born neonates without major problems related to the treatment or to the maternal disease. The relapse rate of the disease recorded during the observation period was 0.07 patient/month, not different from that already reported in SLE patients (pregnant or nonpregnant). Obstetrical complications were relatively frequent, but careful monitoring allowed us to avoid late fetal wastage. We conclude that in SLE patients a successful pregnancy outcome, without worsening of the disease, can be obtained with a careful multidisciplinary follow-up. PMID- 1458697 TI - Antiphospholipid antibodies and complement activation in patients with cerebral ischemia. AB - Antiphospholipid antibodies (aPL) have been linked to stroke and TIA. The mechanism for aPL-associated thrombosis is uncertain, but could be related to complement-mediated membrane damage. Indirect evidence for complement activation (low C4 levels) has been associated with aPL, with variable correlation with disease manifestations. We measured complement activation directly using an ELISA for SC5b-9 in 26 patients with stroke/TIA; 13 with and 13 without aPL. Patient plasma levels of SC5b-9 were measured along with standard positive and 5 normal control samples. Nine patients with, whereas only one without, aPL had an abnormal SC5b-9 level (p = 0.0018, Fisher's Exact Test). These data confirm a relationship between aPL and complement activation, which argues for an active autoimmune process in aPL-associated thrombosis and suggests that complement activation may play a pathogenic role. PMID- 1458698 TI - Anti-enterobacteria antibodies in psoriatic arthritis. AB - The occurrence of certain antibacterial antibodies was studied in the sera of 22 healthy donors (HD) and 66 patients with different diseases. The cases investigated included 22 rheumatoid arthritis (RA), 22 non-arthritic-psoriasis (NAP), and 22 psoriatic arthritis (PA) patients. A complement fixation test was used with Yersinia enterocolitica 0:3 type (YEC), Yersinia pseudotuberculosis (YPT), Campylobacter jejuni (CJ), and Campylobacter fetus (CF) antigens; the detection of anti-Chlamydia trachomatis (CT) antibodies was carried out using an immunoperoxidase colorimetric slide test that allowed the detection of isotypes of specific antibodies. It was found that the synthesis of anti-CF, CJ, YEC, and YPT antibodies in NAP patients does not differ significantly from that of the HD group; on the contrary, the antibody levels were statistically higher in PA than in the other disease groups or in the healthy controls, although only anti-CF antibodies seemed to significantly differentiate (p = 0.000003) the PA group from the others. Anti-CT IgA antibody titers were found to be significantly higher in the PA as well as in the RA groups when compared with the controls, while the antibody levels in NAP patients showed no clear-cut difference with respect to those of either the arthritic patients or the healthy controls. By showing that anti-enterobacterial antibodies are increased in PA but not in NAP patients, our data furnish additional support to the thesis of a pathogenic role of bacterial infections in psoriatic arthritis. PMID- 1458699 TI - Unusual responses to electrocutaneous stimulation in refractory cervicobrachial pain: clues to a neuropathic pathogenesis. AB - Refractory cervicobrachial pain (RCBP) is a common syndrome of uncertain pathogenesis, frequently seen in an occupational context. It is characterised by widespread neck, shoulder girdle and arm pain, often of dysaesthetic quality including burning, associated with paraesthesiae, impaired perception of touch, allodynia, hyperalgesia and hyperpathia. Despite these clinical features, the syndrome has not attracted investigation with other than standard neurophysiological tests. Electrocutaneous electrical stimulation (ECS), following a well-described and validated method, was chosen as a tool to investigate the nociceptive status in RCBP. A commercially available calibrate transcutaneous electrical nerve stimulation (TENS) machine was used to determine perception threshold and pain tolerance with respect to the amplitude of current and duration of pulse. Fifteen patients with typical RCBP and ten normal volunteers were studied. The response profiles obtained were reproducible over time in both patients and controls and were able clearly to distinguish between affected and non-affected limbs. The perception threshold and pain tolerance in the unaffected limbs of patients did not differ from those in normal subjects. In the affected limbs there was reduction in pain tolerance, invariably accompanied by spread of sensation and persistence of dysaesthesiae, both induced by ECS. These results define the limbs affected by RCBP as regions of secondary hyperalgesia at the clinical level. It is suggested that neural dysfunction may be involved in the pathogenesis of RCBP, although a confident distinction between peripheral and central processes cannot be made on the basis of these findings, which call for further investigation. PMID- 1458700 TI - Pneumococcal septic arthritis as the first manifestation of multiple myeloma. AB - In this paper we report a 47 year old woman with septic arthritis due to Streptococcus pneumoniae. No known predisposing factor was found. After an extensive workup a multiple myeloma was discovered. In our case septic arthritis was the first manifestation of multiple myeloma. PMID- 1458701 TI - Raynaud's phenomenon: a proposal for classification. AB - Major confusion exists with regard to the definition of patients with Raynaud's phenomenon; defining the patient and the phenomenon are reasonably straightforward, but variations in the definition of its primary and secondary forms have created a situation in which the same patient might be classified as primary by one group and secondary by another. The present essay is a proposal for the strict definition of Primary Raynaud's Phenomenon (PRP) formulated as a hypothesis amenable to experimental testing. This hypothesis is tested retrospectively on a group of 240 patients with Raynaud's phenomenon. The proposed criteria permit classification in 215 of 240 cases or 89%, leaving 25 patients difficult to classify at initial evaluation. Further testing of the hypothesis is encouraged. PMID- 1458702 TI - Sneddon's syndrome. AB - Sneddon's syndrome refers to the rare association of extensive livedo reticularis with multiple ischaemic cerebrovascular episodes. Endarteritis obliterans is the most common cutaneous pathology. It is likely that several pathogenic mechanisms may give rise to Sneddon's syndrome, as the condition is associated with a high incidence of generalised atherosclerosis, hypertension, valvular heart disease and the presence of antiphospholipid antibodies. PMID- 1458703 TI - Serum interleukin-6 levels and joint involvement in polyarticular and pauciarticular juvenile chronic arthritis. AB - We measured serum and synovial fluid interleukin 6 (IL-6) levels in patients with polyarticular-onset and pauciarticular-onset juvenile chronic arthritis (JCA), using the hybridoma cell line B9. During active disease, but not during remission, serum IL-6 levels were significantly elevated in patients with polyarticular (p < 0.0001 vs controls) and in patients with pauciarticular JCA (p < 0.01 vs controls). In patients with active polyarticular disease (polyarticular and extended pauciarticular) serum IL-6 levels correlated with the extent and severity of joint involvement (p < 0.05), with erythrocyte sedimentation rate values (p < 0.005) and with C reactive protein concentrations (p < 0.05). In patients with persistent pauciarticular JCA, serum IL-6 levels correlated with the joint swelling score (p < 0.05). Synovial fluid IL-6 levels, measured in 5 patients with pauciarticular JCA, were markedly elevated (range 600-24,000 HGF U/ml). In conclusion, our data suggest that IL-6 is an important pathogenic mediator in polyarticular and pauciarticular JCA. PMID- 1458704 TI - Coexistence of myasthenia gravis and seropositive juvenile chronic arthritis. AB - The development of myasthenia gravis (MG) in a patient with juvenile chronic arthritis (JCA) is a rare occurrence. This report concerns a patient with seropositive JCA who developed MG during her second pregnancy. PMID- 1458705 TI - IL-2, IL-6 and TNF levels in primary antiphospholipid syndrome. PMID- 1458706 TI - Comment on a model of type II collagen-immune complex arthritis in sheep. PMID- 1458707 TI - The Consensus Workshops for the Detection of Autoantibodies to Intracellular Antigens in Rheumatic Diseases: 1989-1992. AB - The European Consensus Study Group for Autoantibodies was formed in 1988 to examine test systems for the detection of autoantibodies found in patients with rheumatic and related conditions. In the last four years it has organised an annual exercise to examine the sensitivity and reproducibility of different methodologies for the detection of these antibodies, and the concordance obtained between leading laboratories in Europe. The results of these exercises show an improvement in detection rates. In addition, the group has produced a methodology handbook, containing recommended methods as used by expert laboratories, and has made recommendations on the performance of assays for the detection of autoantibodies. PMID- 1458708 TI - Disease activity in rheumatoid arthritis: preliminary report of the Consensus Study Group of the European Workshop for Rheumatology Research. AB - The most suitable measures to assess the disease activity of rheumatoid arthritis patients treated with slow-acting anti-rheumatic drugs were considered in a prospective study. This was organised across Europe in 12 specialised centres and 282 patients were studied. The patients were all considered to be in need of therapy with a slow-acting anti-rheumatic drug and were studied at the initiation of therapy, and after 3 and 6 months of treatment. There were 215 patients who remained on treatment for 6 months. The most useful measures to assess disease activity were: the number of swollen joints, the number of tender joints, pain, the patients' assessment of response, and ESR. These should form a minimum data set when assessing the activity of rheumatoid arthritis. Some measures such as grip strength, hemoglobin, and the C-reactive protein level showed too much variation between centres and will require considerable standardisation before they can be used across Europe. There were problems in collecting functional data and further work is needed to develop a functional questionnaire available in all European languages with culturally suitable questions. PMID- 1458709 TI - Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. I. A descriptive analysis of 704 European lupus patients. European Consensus Study Group for Disease Activity in SLE. AB - Using a detailed questionnaire, the cumulative historical and current demographic, clinical and serological data on 704 SLE patients from 29 European centres and 14 countries have been assessed. Ninety-three percent of the patients were Caucasian and the female/male ratio was 10:1. Analysis of the cumulative incidence showed that arthralgia/arthritis (94%), rash (69%), Raynaud's phenomenon (49%), serositis (44%) and renal disease (38%) were the most frequent clinical manifestations. Virtually all the patients (98%) were antinuclear antibody positive, while anti-ds-DNA antibodies (76%), hypocomplementaemia (71%) and anti-Ro(SSA) antibodies (35%) were frequent serological abnormalities. Whilst much of this data is in line with previous reports, it is notable that renal, lung, and central nervous system involvement and the frequency of rheumatoid factor, anti-Sm and anti-RNP antibodies were much lower than in most comparable series in the United States. We assume that ethnic differences and the greater present awareness of lupus could explain this variations. Low dose corticosteroids, non-steroidal anti-inflammatory drugs and anti-malarials were used to treat over half of the patients, 75% of whom were between 15 and 55 years of age. This report offers a useful overview of lupus both clinically and serologically in Europe in the 1990's. PMID- 1458710 TI - Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE. AB - A European Consensus Group study, involving 29 centres from 14 countries, was performed in order to reach agreement on the definition of disease activity in systemic lupus erythematosus (SLE) and to construct a new disease index. Data on 704 lupus patients were collected and analysed, using univariate and multivariate statistical procedures, to select those clinical and laboratory features of the disorder which best correlate with the global assessment of disease activity assigned to the patients by the physician of each participating centre. A combination of 15 clinical and laboratory variables was shown to be the best predictor of disease activity in SLE. A European Consensus Lupus Activity Measurement (ECLAM) was then formulated. This index included the 15 selected variables, weighted (with some adjustments) according to their respective regression coefficients in the multivariate model. ECLAM appears to be an effective instrument for scoring patients with different degrees of disease activity. This is the first SLE disease activity index based on data from a very large number of lupus patients followed at a large number of lupus centres in different countries. It might therefore very well serve as a standardised measure for future European clinical studies. Final assessment of the validity, reliability and sensitivity of this index is now underway. PMID- 1458712 TI - The clinical significance of hemoglobinopathies in the Hamilton region: a twenty year review. AB - Between 1970-1990, the Laboratory tested 38,391 specimens for hemoglobinopathies, of which 7,935 were positive. The major abnormalities detected were beta thalassemia trait (4,688), alpha thalassemia trait (1,248) and sickle cell trait (847). Clinically significant hemoglobinopathies detected were Hemoglobin H disease (100), sickle cell disease (67) and sickle cell Hemoglobin C disease (79). Hemoglobinopathies are therefore common in the Hamilton area as a reflection of the cultural diversity of area citizens. Of the 49 patients with thalassemia without documented iron deficiency, 8 (16%) received iron therapy for a variable period of time and 3 were investigated for gastrointestinal blood loss. Hemoglobin abnormalities cause or have the potential to cause clinical disease and they can, if not detected, result in unnecessary iron therapy or gastrointestinal investigation. PMID- 1458711 TI - Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. III. Development of a computerised clinical chart and its application to the comparison of different indices of disease activity. The European Consensus Study Group for Disease Activity in SLE. AB - In the first phase of this study, a data-base containing clinical and laboratory findings of 704 patients with systemic lupus erythematosus (SLE), originating from 29 centres and 14 countries, was used to assess the validity of 4 common indices of disease activity, SLAM, BILAG, SLEDAI and SIS. The physician's judgement of activity was assumed as the unique reference criterion (gold standard). Computer programmes were developed to calculate automatically the 4 activity indices; this computation appeared to correspond with manual computations in a sample of 60 appropriately selected cases. All 4 indices were closely correlated with each other (r in the range of 0.716 to 0.872), and with the physician's score (r in the range of 0.620 to 0.719). In the second phase of the study the activity index developed in part I (ECLAM) was prospectively validated, and its performance compared to that of the other scales, both as a single state index and as a transition index (i.e., its ability to assess disease activity at a single point in time and to detect variations in consecutive readings). A computer-assisted clinical chart was prepared for this purpose. This chart allowed us to calculate automatically all the indices. Two consecutive observation times (time 0, and time 1 three months later) were included in the study protocol. Data on 75 patients from 19 centres were collected, and each patient was observed twice. All the computed indices were closely correlated, both at time 0 (r ranging from 0.725 to 0.884), and at time 1 (r ranging from 0.607 to 0.833).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458713 TI - Glucose turnover and its regulation during intense exercise and recovery in normal male subjects. AB - Intense exercise to exhaustion is expected to be associated with rapid and large changes in glucose production (Ra) and utilization (Rd). To quantify these, and to determine their mechanisms and those of the prolonged postexercise hyperglycemia, we measured circulating metabolic regulators and glucose kinetics, the latter by the method of enriched tracer [3-3H] glucose infusion during exercise. Eighteen fit, lean young male subjects exercised to exhaustion at 80% of maximal workload (approximately 100% VO2max) on a cycle ergometer. Plasma glucose was 4.90 +/- 0.08 mM/L at rest, increased during exercise, then abruptly to 6.91 +/- 0.40 mM/L at 4 min recovery then gradually declined. Plasma insulin was constant during exercise, then doubled to 162 +/- 28 pmol/l until 20 min recovery, before declining. Plasma glucagon increased by 71 +/- 11 pg/mL. Plasma norepinephrine increased 18-fold and epinephrine 14-fold, both declining by 20 min recovery. Ra increased 7-fold by exhaustion to 13.0 +/- 1.18 mg/kg/min, then decreased to 2.43 +/- 0.24 mg/kg/min by 9 min, then to about 2 mg/kg/min the rest of recovery. Rd rose 3-fold (6.61 +/- 0.70 mg/kg/min), and remained lower than Ra to 7 min recovery, but thereafter declined more slowly. Thus, the rapid and extremely large increase in Ra was not matched by the increment in Rd during exercise and early recovery. We suggest that unlike in exercise of lesser intensity, the major mediators of both the increase in Ra and the restraint of the increase in Rd are the catecholamines. The post exercise hyperglycemia and hyperinsulinemia are appropriate to muscle glycogen repletion. PMID- 1458714 TI - Pharmacokinetic study of intraperitoneal streptozotocin. AB - Streptozotocin, a nitrosourea, has limited antitumour activity. However, in concentrations and exposures higher than those achieved after intravenous dosing, streptozotocin has been reported to sensitize various cell lines in vitro to other nitrosoureas or alkylating agents. We hypothesized that the intraperitoneal administration of streptozotocin would achieve concentrations and exposures in the peritoneal cavity sufficient for this sensitization to take place. The pharmacokinetics of streptozotocin in the peritoneal cavity and in plasma were determined in patients who received 1 g of streptozotocin via the intraperitoneal route. Fifteen courses were administered to 12 patients. The mean total area under the concentration versus time curves (AUC) was 183 +/- 31 (SE) mM min in the peritoneal cavity (5 courses) and 5.3 +/- 1.1 (SE) mM min in plasma (6 courses). The mean peritoneal to plasma AUC ratio was 64 +/- 23 (5 courses). The mean peak streptozotocin concentrations in the peritoneal cavity (5 courses) and plasma (6 courses) were 1.9 +/- 0.4 mM and 0.03 +/- 0.01 mM, respectively. No significant toxicity was observed on any course. We conclude that intraperitoneal administration of streptozotocin is feasible, and that drug concentrations and exposures are in an appropriate range in the peritoneal cavity to cause sensitization to other nitrosoureas. PMID- 1458715 TI - Double-blind randomized controlled trial of flurbiprofen-SR (ANSAID-SR) and diclofenac sodium-SR (Voltaren-SR) in the treatment of osteoarthritis. AB - A six week, double-blind, randomized, parallel group, multicentre study was conducted in 85 patients with osteoarthritis of the knee and hip to compare the efficacy, tolerability, and safety of Flurbiprofen-SR 200 mg with Diclofenac Sodium-SR 100 mg. Between group comparisons, based on change scores from baseline, we detected no significant differences between the two drugs with respect to efficacy for the majority of outcome measures. There was no significant difference between the groups in the proportion of patients experiencing at least one adverse medical event or in terminations from treatment. We conclude that Flurbiprofen-SR 200 mg is similar in efficacy, tolerability, and safety to Diclofenac Sodium-SR in this trial. PMID- 1458716 TI - The comparative efficacy of cilofungin, fluconazole and amphotericin B in disseminated Candida tropicalis infection in neutropenic mice. AB - There is insufficient in vivo data on the efficacy of new antifungal agents against invasive Candida tropicalis infection. Disseminated infection with Candida tropicalis in neutropenic mice was treated with cilofungin, fluconazole, or amphotericin B intraperitoneally, and compared to untreated controls. Early survival rates at the end of treatment (day 10) were similar for amphotericin B (97.5%) and fluconazole (100%), and superior to cilofungin (62.6%) which was better than no treatment (0%). Late survival rates (day 31) were highest for amphotericin B (95%), and significantly lower for cilofungin (48.7%) and fluconazole (43.9%), p = 0.0001. Rates of sterilization of the lung, liver, and spleen were high in survivors for all regimens (85.1-100%) but lower for the kidneys: fluconazole, 21.3%; amphotericin B, 39.3%; and cilofungin, 65.5%. Amphotericin B was the most effective agent in this study of disseminated Candida tropicalis (C. tropicalis) infection. PMID- 1458717 TI - Knowledge of nephrologists and patients about autosomal dominant polycystic kidney disease (ADPKD). AB - Because of the availability of presymptomatic testing for autosomal dominant polycystic kidney disease (ADPKD), we assessed the response of nephrologists, patients, and at-risk relatives to the introduction of a genetic counselling program for ADPKD. Fifty-six of seventy-six nephrologists responded. Ninety-eight percent reported 'generally' telling their patients that the disease was hereditary, but fewer reported screening relatives (81% for children and 70% for siblings and parents). Ninety percent were interested in referring patients to the service. Fourteen of the 24 patients in one renal clinic and 18 of their at risk relatives were interviewed. Ten of the patients but only five of the relatives stated that the disease was hereditary. The precise mechanism of inheritance was poorly understood by most patients and relatives. Of 21 patients offered genetic counselling, nine made appointments to see the genetic counsellor. There remains a large gap between advancing technology and the delivery of information to at-risk populations. PMID- 1458718 TI - Adenosine as a therapeutic agent. AB - Adenosine, an endogenous nucleoside has been recently approved for use in the treatment of paroxysmal supraventricular tachycardia. Adenosine is nearly 100% effective in terminating tachycardia in which the atrioventricular node forms part of the reentrant circuit. Although most ventricular tachycardias are insensitive to adenosine, this substance is effective in ventricular tachycardia induced by catecholamines or exercise. An intravenous bolus dose of 6 mg is the initial dose. If no effect is noted a further bolus of 12 mg can be given. The most common side effects are dyspnea, chest pressure and facial flushing. This article reviews, in addition, some of the comparative trials with verapamil and adenosine triphosphate, some of the additional therapeutic indications, the possible mechanisms of action in cardiac tissue, and the type of purinergic receptors involved in the antiarrhythmic effects of adenosine. PMID- 1458719 TI - Androgen resistance due to mutation of the androgen receptor. AB - The androgen receptor (AR) is a 'one-stop' signal transduction system that is the core of the intracellular androgen-response apparatus. It is an androgen regulated, DNA-binding protein that regulates the expression of certain target genes, primarily at the transcriptional level. Mutations at the X-linked AR locus cause deficient or defective AR activity and, thereby, an extraordinarily wide spectrum of clinical androgen resistance. At one extreme, the affected 46,XY person is an infertile phenotypic female; at the other, he is a phenotypic male who may even be fertile, yet have gynecomastia or other focal signs of postpubertal subvirilization. We have identified 32 proven or putatively pathogenic alterations in the AR gene of 38 androgen-resistant families. This permits heterozygote detection and prenatal diagnosis whenever relevant. Most of the mutations affect the AR's androgen-binding domain, partly because our search has been targetted on those whose genital skin fibroblasts have impaired androgen binding activities. The AR is a prototypic member of a subfamily that includes the receptors for progesterone, glucocorticoid, and mineralocorticoid. Observations that correlate AR genotype with clinical and receptor phenotypes of androgen resistance will help to generate a fine structure-function map of the AR and its close relatives. Constitutional variation in androgen sensitivity, that may be restricted to an organ (or organ system), could contribute to the pathogenesis of certain diseases whose sex ratio departs significantly from one. PMID- 1458720 TI - Right atrial myxoma: an unusual presentation. PMID- 1458721 TI - Physicians' perceptions of laboratory costs in the intensive care unit. Hamilton Regional Critical Care Group. AB - Our objective was to determine the extent to which Intensive Care Unit (ICU) physicians are aware of charges for commonly used blood tests. We also wished to ascertain ICU physicians' perception of their motivation for, and appropriateness of, test ordering. Attending physicians and Internal Medicine residents in four university-affiliated ICUs in Hamilton were surveyed using a self-administered questionnaire. The response rate for the questionnaire was 91%. Physicians varied widely in their estimates of charges for ten laboratory tests. On average, residents tended to underestimate charges, while attending physicians sometimes underestimated, and sometimes overestimated. When all ten tests were considered, the mean estimates of the housestaff were lower than the ICU attending physicians (p < 0.001). Overall, attending estimates were 29.5% higher. Over 85% of physicians felt that too many blood tests were being performed. Physicians perceived that they pay insufficient attention to the risk of anemia and to issue of cost. Their feeling that test ordering in the ICU is excessive suggests that they may be open to modifying their practice. Given the large proportion of hospital resources allocated to the intensive care unit, interventions to decrease test ordering are warranted. PMID- 1458722 TI - [Studies on motor neuron disease with cranial magnetic resonance imaging]. AB - The present study was performed to examine the pyramidal tracts of the brain in both 51 normal subjects (21 male and 30 female subjects; mean age of 43.5 +/- 16.1 years) and 12 patients with motor neuron disease (6 male and 6 female patients; mean age of 57.4 +/- 7.9 years), using the magnetic resonance imaging (MRI). The 12 patients with motor neuron disease (MND) comprised 7 suffering from spinal progressive muscular atrophy (SPMA) and 5 from amyotrophic lateral sclerosis (ALS). The MRI used in this study was of both short spin echo and long spin echo sequence. Of the 52 normal subjects, 24 of them (47%) had the T2 prolonged small areas (high signal intensity areas) at the posterior limb of internal capsule. These findings were not found in the normal subjects over fifty years old. No similar finding was detected in the pyramidal tracts except the posterior limb of internal capsule. On the other hand, 8 patients with MND (67%) proved to have the high signal intensity areas in the pyramidal tracts. Moreover, these high intensity areas were extended from the crus cerebri to corona radiata in 7 patients (58%). In all patients with ALS, these areas were extended in whole areas of the pyramidal tracts, and the similar findings were also found in two patients with SPMA. These findings were demonstrated to be more extensive than those in the normal subjects. The results thus obtained warrant us to conclude that cranial MRI is useful to detect the degeneration of the pyramidal tracts of MND patients. PMID- 1458723 TI - [Interleukin-2 production by peripheral blood mononuclear cell from patients with myasthenia gravis--correlation with clinical severity]. AB - Interleukin-2 (IL-2) production by peripheral blood mononuclear cell (PBM) and the frequency of surface IgG+ B cells (%) were studied in 17 patients with myasthenia gravis (MG) and 12 controls. Culture supernatants from phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cell from patients with MG and controls were added to IL-2 dependent proliferative cultures (CTLL-2). Following 24 hr of culture, 3H-Tdr was added and cultured for an additional 6 hr. Cultures were harvested and 3H-Tdr incorporation was determined. In comparison with controls we found significantly increased synthesis of IL-2 in patients with MG (p < 0.05). Highest synthesis was found in severe cases and there were highly significant correlation between IL-2 synthesis and clinical severity score (R = 0.85, p < 0.05). These findings suggest that the ability of IL-2 synthesis by PBM may reflect severity of patients with MG. B cells expressing surface IgG, considered to be differentiated B cells, were less frequent in severe cases (R = -0.67, p < 0.05). It may be that the B cells with further differentiation are transformed into plasma cells expressing other markers such as PCA-1 in severe patients with MG. PMID- 1458724 TI - [Correlation between clinical features and neuroradiological findings in juvenile muscular atrophy of unilateral upper extremity (Hirayama disease)--with and without "tight dural canal in flexion"]. AB - Myelography was performed in 12 patients with juvenile muscular atrophy of unilateral upper extremity. Seven patients showed anterior shift of lower cervical dural canal in flexion (tight dural canal in flexion) (T group), however the other 5 patients did not show "tight dural canal in flexion" (NT group). Onset of illness and sex were not different between 2 groups. However, there was a tendency that the neurological signs and symptoms were more severe in the patients of T group than those of NT group. These results suggest that "right dural canal in flexion" can be one of mechanisms which exhibit the clinical symptoms of the juvenile muscular atrophy of unilateral upper extremity. However, there may be other etiological factors in the juvenile muscular atrophy of unilateral upper extremity. PMID- 1458725 TI - [A case of ceruloplasmin deficiency which showed dementia, ataxia and iron deposition in the brain]. AB - A 55-year-old female with progressed dementia, cerebellar ataxia was reported. There was no family history of the same symptoms although her brothers, sisters and a son showed hypoceruloplasminemia and decrease of the serum copper content. On physical examination, anemia, dementia, dysarthria, torticollis, choreic involuntary movement of respiratory muscles, hyperreflexia in extremities and cerebellar ataxia were noted. Blood analysis revealed microcytic hypochromic anemia, diabetes mellitus, decrease of copper content of the serum and urine. Serum ferritin concentration was increased. Serum ceruloplasmin could not be detected. Biopsy of the liver showed that copper content in the liver was slightly increased and iron content was remarkably increased. On MRI study, dentate nucleus of the cerebellum, the thalamus, the putamen and the caudate nucleus and the liver showed low intensity in both T1 and T2 weighted images. Based on increased iron content in the liver, the radiological findings of the brain suggested deposition of iron in the brain. This deposition was considered as caused by deficiency of function of ceruloplasmin as ferroxidase. This disorder is suggested as a new disease due to ceruloplasmin deficiency different from Wilson's disease. PMID- 1458726 TI - [An autopsy case of chronic inflammatory demyelinating polyradiculoneuropathy with sever degeneration in the posterior column]. AB - An autopsy case of chronic inflammatory demyelinating polyradiculoneuropathy was reported. It took a progressive course and terminated fatally in eight years. A 41-year-old man noticed motor disturbances when he tried to lift a bath pail and to write on July, 1978. Neurological examination revealed proximal dominant muscle atrophy, weakness of all extremities, and moderately diminished tendon reflex. Sensation was normal. The CSF showed albumin cytologic dissociations. Electromyogram showed neurogenic changes. Histological examination of biopsy specimen obtained from the anterior tibial muscle revealed severe neurogenic changes and showed axonal degeneration on the ventral tibial nerve. The treatment by corticosteroids was not effective, and the disease gradually progressed with repeated improvements and exacerbations. Three years after the onset, he showed vesicorectal dysfunctions. He died of respiratory failure on May, 1986. Neuropathological examination showed severe degeneration of middle root zones in the posterior columns, loss of myelinated fibers in Clarke's columns, demyelination and mild loss of axons accompanied by lymphocytic infiltration in the spinal roots, especially in the anterior roots. The histogram of cervical ventral root, ventral and dorsal roots of thoracic and lumbar regions revealed a decreased number of large myelinated fibers. A characteristic finding of this case was the dissociation of clinical features and neuropathological findings; the clinical features showed a typical motor neuropathy, but neuropathological examination showed severe degeneration on posterior columns of spinal cord like a sensory-ataxic neuropathy. Our observation suggest that the pathway which originates from posterior ganglion cells and runs into Clarke's columns passes through the middle root zones, since severe demyelination in Clarke's columns was observed. PMID- 1458727 TI - [A case of autoimmune polyglandular deficiency associated with progressive myopathy]. AB - We reported a 29-year-old woman with autoimmune polyglandular deficiency (APGD) type 1 accompanied by progressive myopathy. She had chronic mucocutaneous candidiasis at the age of 3, primary hypothyroidism at 12, insulin dependent diabetes mellitus at 27, and adrenal insufficiency at 29 years. Laboratory findings indicated an underlying defect in cell mediated immunity. Meanwhile, she had progressive muscular weakness and wasting at the age of 22 years which brought her to our hospital at 29 years. On admission, she could not walk without support and raise her arms up to the level of shoulders. Moderate to severe muscle wasting as well as weakness was observed in the limb girdle muscles. Serum CK levels were mildly elevated. A needle EMG examination disclosed short-duration and low-amplitude polyphasic motor units at voluntary contraction with few fibrillations and positive sharp waves at rest. On muscle CT examination, decreased density was detected in the neck extensor, paravertebral, rectus femoris, vastus intermedius, biceps femoris and soleus muscles. Muscle biopsy was performed on the biceps brachii and rectus femoris muscles. The former showed chronic dystrophic changes including marked variation in fiber size with necrotic and degenerating process, interstitial fibrosis, and lobulated and right fibers. In the latter, in addition to variation in fiber size with some necrotic fibers and occasional multi-core structures, nemaline bodies were seen in approximately 30% of muscle fibers. The progressive muscle involvement in our patient might be induced from 1) endocrine abnormality, 2) autoimmune disorder, and/or 3) coincidental complication of nemaline myopathy or limb girdle muscular dystrophy. The clinical and laboratory examinations, however, failed to support any of them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458728 TI - [A case of monoballism in unilateral lower extremity--somatotopic relation in subthalamic nucleus]. AB - A 62-year-old man with monoballism in the right lower extremity was reported. The cranial MRI showed a small lesion affecting the posterior portion of the contralateral subthalamic nucleus. Superficial EMG recording revealed 1-2 Hz rhythmic grouping discharges in right quadriceps femoris, hamstrings, tibialis anterior and gastrocnemius-soleus. In the vast majority of cases, ballistic movements involved both upper and lower extremities of one side (hemiballism), but the present case showed monoballism in the lower extremity only. Previous reports suggested the somatotopy mapping subthalamic nucleus; the posterior portion being associated with the lower extremity, middle part with the upper extremity and the oral pole with the face. In the present case, the affected part of subthalamic nucleus was towards its posterior portion and it seemed legitimate to associate such topographic location of the lesion with the absence of involuntary movements in the upper extremity and the face. Coronal and axial sections of high-field MR scans were useful for the detection of the responsible lesion. PMID- 1458729 TI - [Central type of sleep apnea syndrome caused by unilateral lateral medullary infarction]. AB - We reported here a 64-year-old man with a central apnea resulted from unilateral medullary infarction. He was admitted because of cerebellar ataxia, dysarthria and dysphasia of abrupt onset. After the injection of diazepam for alcohol forbidden syndrome, he induced complete apnea and required the endotracheal intubation. At the spontaneous respiration under room air, his arterial blood gas showed hypercapnea without hypoxemia, and he fell into severe hypoventilation when hypnotic drug was injected. Respisomnogram revealed the frequent presence of central apnea both while he was awake and asleep. MRI demonstrated an abnormal high intensity area on T2 weighted image at the right lateral medulla just below the ponto-medullary junction. At autopsy, areas of the infarction were limited within the right lateral medulla, including lateral portion of the medullary reticular formation, the ambigual nucleus, one part of the solitary nuclear complex, the inferior cerebellar peduncle and the spinal trigeminal nucleus. However, the dorsomotor nucleus of vagus was completely free from the infarct lesion. There was no other lesion within central nervous system. Such a distribution seemed the minimal extent of the lesion responsible for central, apnea compared to the previous reports. We suggest that central apnea occurs not infrequently in the cases of Wallenberg's syndrome. PMID- 1458730 TI - [Intra-abdominal visceral fat in myotonic dystrophy]. AB - We first clarified the relationship between abdominal visceral fat accumulation and impaired glucose and lipid metabolism in patients with myotonic dystrophy. Nineteen patients aged 44.2 +/- 11.4 years with a body mass index (BMI) of 20.5 +/- 2.8 kg/m2, and 18 controls aged 45.2 +/- 10.3 years, with a BMI 20.0 +/- 2.8 kg/m2 were examined. The distribution of abdominal visceral and subcutaneous fat was examined by CT scanning at the umbilical level. Visceral fat area was significantly greater in myotonic dystrophy than that in control (p < 0.05), and positively correlated with the levels of fasting plasma glucose (r = 0.65 p < 0.01), plasma glucose area under the curve of 75 g oral glucose tolerance test (r = 0.67 p < 0.01), fasting plasma insulin (r = 0.77 p < 0.001), serum total cholesterol (r = 0.71 p < 0.001) and serum triglyceride (r = 0.68 p < 0.01). From the present results, we speculate that excess visceral fat accumulation in myotonic dystrophy induces impaired glucose and lipid metabolism. PMID- 1458731 TI - [A case of multiple cranial nerve palsy with severe dysphagia due to herpes zoster infection]. AB - A case of multiple cranial nerve palsy by herpes zoster was reported. A 79-year old man showed fever, sore throat, and dysphagia. No vesicle was noted at ear and pharynx. The patient developed, later, left peripheral facial nerve palsy. The cerebrospinal fluid revealed pleocytosis with increased protein. The viral antibody titer of herpes zoster was significantly elevated both in cerebrospinal fluid and in serum. The left facial palsy was slightly improved. But his dysphagia didn't improve during at least 10 months after the onset. Among the cranial nerves, trigeminal and facial nerves are the most commonly affected by herpes zoster. But there are a few cases of the 9th and 10th cranial nerve involvement in the literature. However, dysphagia has rarely been reported in these previous cases, only four cases developed severe dysphagia like the present patient. All of these cases including our case were over sixty years old, while cases with slight dysphagia were under sixty years old. No other differentiating factor is noted between these two groups with regard to sites of vesicles, findings of cerebrospinal fluid and mode of therapy. PMID- 1458732 TI - [A case of bilateral blepharospasm responsive to edrophonium]. AB - A case of bilateral blepharospasm who registered the efficacy of edrophonium was reported. The case is a 49-year-old female. She had been in good health until January, 1991 when she complained of difficulty in opening her eyes while driving. Thereafter the condition progressed to such a degree that she was unable to experience a comfortable life. Her blinking rate did not changed. The symptoms were triggered by stress or some physical action, such as walking or driving. They were attenuated by taking a bath, sleep or sedation. The severity of the symptoms varied during the day and from day to day. Neurological examination revealed bilateral spasms of the orbicular oculi muscles, and occasionally of the orbicular oris muscles, sternocleidmastoid muscles and the perinasal regions. Neither orolingual dyskinesia nor other involuntary movements were detected. Surface electromyography (EMG) disclosed tonic discharges mainly from the orbicular oculi muscles. The abnormal spasm disappeared with the injection of edrophonium chloride. The test for the serum antiacetylcholine receptor antibody was negative and a repetitive stimulation EMG showed no waning phenomenon. No thymoma or thymus abnormalities were detected by pneumomediastinography. A needle EMG revealed neurogenic change in the distal portion of the limbs. A single fiber EMG showed elongation of the jitter value and the blocking phenomenon. Although distigmine bromide was ineffective against the spasm, pyridostigmine bromide and the local injection of botulinum toxin were very effective.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458733 TI - [Cerebrospinal fluid neuron-specific enolase (NSE) and S-100b protein in Guillain Barre syndrome--their relations to prognosis]. AB - We measured the cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) using enzyme immunoassay methods in 12 patients with Guillain-Barre syndrome (GBS), and 46 control subjects, and evaluated their clinical values in relation to prognosis. The 4 patients with the remarkably elevated level of NSE or S-100b in the acute stage recovered slowly over 1 year after onset, while the 2 patients showed the normal NSE and S-100b levels and recovered within 4 months. In 6 patients, the NSE and/or S-100b were slightly or moderately increased in the acute stage. They recovered from 1.5 to 11 months after onset, and the two patients showing very early recovery have the remarkably increase of S-100b in the recovery stage. These results suggest that CSF NSE and S-100b may be useful biochemical markers for estimation of prognosis in GBS patients. PMID- 1458734 TI - [Two sibling patients with late-onset familial amyloidotic polyneuropathy and atypical clinical manifestations]. AB - Brothers (case 1 and case 2) had familial amyloidotic polyneuropathy type 1 (FAP type 1) confirmed with sural nerve biopsy and DNA analysis. Both patients were unique in that their ages at onset were 56 and 52, and that their only manifestation was sensori-motor polyneuropathy, without clinically apparent autonomic involvements such as orthostatic hypotension, sweat dysfunction and sphincter dysfunction, or severe organ involvement such as gastrointestinal features and myocardial involvement after the onset. They are also unique in that their parents were healthy. The initial manifestation was sensori-motor polyneuropathy starting in the lower extremities. These atypical manifestations made the diagnosis of FAP type 1 difficult in the present cases. Based on reports in the literature and the present cases, there might be a tendency that in patients with late-onset FAP type 1 the clinical manifestations are generally mild and autonomic involvement and organ disturbance are absent or mild. In the etiological diagnosis of polyneuropathy, FAP type 1 should be considered especially in steadily progressive patients. PMID- 1458735 TI - [Isolated abducens nerve palsy caused by pontine infarction]. AB - An 82-year-old hypertensive man suddenly developed diplopia during right lateral gaze. Neurological examination revealed right isolated abducens nerve palsy without any other findings. By cranial CT scan, a low density area over the posterior limb of right internal capsule and tortuosity of basilar artery were noted. 3 months later, his symptom disappeared and then he was well in next 2 years til he felt diplopia during left lateral gaze. On this time he showed left isolated abducens nerve palsy. Though cranial CT scan failed to find out new abnormality, T2-weighted cranial MRI disclosed high intensity spot over left pontine base located between medial lemniscus and pyramidal tract, which was supposed to coincide to fascicle of left abducens nerve Three months later, he recovered in the same manner as 2 years before. Hemilateral isolated abducens nerve palsy may be caused by many origins, but pontine infarct was not detected so much in pre-MRI era. Being the long-term prognosis of the lacunar infarction not satisfactory, it is important for the cases of isolated abducens palsy to ascertain whether there is pontine small infarction or not. So in these cases, precise examination including MRI should be needed. PMID- 1458736 TI - [Defect of taste in a patient with hypothyroidism]. AB - A 74-year-old male presented with a total loss of taste of ten weeks' duration. He could not recognize both saturated sugar and salt solutions but his acuity for smell was normal. He also had a slight hoarseness, mild dysarthria and hyporeflexia of all extremities. Laboratory data revealed marked hypothyroidism and positive tests for antithyroglobulin and antimicrosomal antibodies. Shortly after the institution of thyroxine replacement, subjective response in taste acuity was seen. Almost complete recovery of taste followed after a month of incremental dose of thyroxine. The case indicates that thyroid hormones play a significant role in taste acuity. Hypothyroidism should be considered as one of the possible causes in taste defect. PMID- 1458737 TI - Pituitary tumors: an endocrinological and neurosurgical challenge. PMID- 1458738 TI - Reoperation for intractable seizures. PMID- 1458739 TI - Reoperation for aneurysms and vascular malformations. PMID- 1458740 TI - Surgery for recurrent lumbar disc herniation. PMID- 1458741 TI - Reoperation for extra-axial brain tumors. PMID- 1458742 TI - The education of a neurosurgeon: the two cultures revisited. PMID- 1458744 TI - Radiosurgery for intracranial vascular malformations: techniques, results, and complications. PMID- 1458743 TI - Reoperation of the cervical spine for degenerative disease and tumor. AB - Despite improvements in treatment for cervical spine disease over the last decade, failure that requires a reoperative procedure may represent up to 14% of the cases. With the exception of posterior foraminotomy, the most common failure that requires intervention is instability, which results in an anterior compression of the neural elements. With the advent of new operative approaches and innovative stabilization techniques, the options available to treat these patients have improved. PMID- 1458745 TI - Stereotactic radiosurgery in the treatment of brain tumors. PMID- 1458746 TI - Clinical decision making in spinal stabilization. PMID- 1458747 TI - Image-based functional neurosurgery. AB - The development of computerized tomography and compatible stereotactic frame and localization devices has improved the ease and accuracy of functional stereotactic neurosurgery. Computerized tomograph-directed functional stereotaxy appears to be a safe and effective means of target development. Magnetic resonance imaging holds the promise of greater anatomical definition and direct sagittal imaging. Significant questions remain, however, concerning the reliability of MRI-based stereotactic neurosurgery, and these must be addressed. Presently, these techniques should be viewed as a means to localize a target region, not the target per se, and, as stated by Apuzzo, "It is not envisioned, however, that the need for intraoperative stimulation will be mitigated by such refinements." PMID- 1458748 TI - Endovascular treatment of intracerebral arteriovenous malformations. PMID- 1458749 TI - Endovascular treatment of intracranial aneurysms and cerebral vasospasm. PMID- 1458750 TI - Decision making in lumbar disc disease. AB - When a patient presents with an acute pain syndrome suggestive of a herniated lumbar disc, nonoperative treatment is almost always the rule. Urgent surgery is undertaken for intractable pain, significant or progressive neurological deficit, and abnormalities of bowel, bladder, or sexual function. Evaluation of the patient is not needed in typical cases until nonoperative care has failed. The decision to evaluate and treat by intervention is made after a reasonable time, usually a minimum of 1 month and a maximum of 3 for the patient who is not making progress. Slow recoveries can be monitored for even longer if agreeable with the patient. The decision for intervention is almost never warranted in the face of normal imaging studies. Several interventions are possible. Traditional surgery, with or without magnification, is followed by an excellent outcome. Chymopapain injection is a reasonable alternative for those expert in its use. Percutaneous discectomy is a possibility but remains to be proved by acceptable clinical studies. Lumbar disc surgery is highly successful and complications are extremely unusual. They do occur however, and can be extremely serious. Unexpected postoperative complications should be investigated immediately. Recovery from disc surgery usually is uneventful, and no rehabilitation is required. Some patients, particularly those who do heavy work, can be helped by a rehabilitation program that stresses return to normal function. Rarely will a patient develop a serious neurological deficit following surgery. Unexpected serious deficits require urgent reevaluation. Most patients return to work promptly without assistance. For those who cannot, referral to a multidisciplinary rehabilitation program to assist with return to function through general management of comorbidities can be useful. It is a rare patient who is disabled by a back disorder, and the decision that a patient is disabled should be made only after thorough evaluation and adequate rehabilitative therapy. PMID- 1458751 TI - Intramedullary neoplasms and vascular malformations. PMID- 1458752 TI - Interventional neuroradiology for spinal pathology. PMID- 1458753 TI - Osseointegration in spinal stabilization. PMID- 1458754 TI - Imaging and functional localization for brain tumors. PMID- 1458755 TI - Surgical management of pineal region tumors (honored guest lecture). PMID- 1458756 TI - Clinical decision making in epilepsy surgery. PMID- 1458757 TI - Problems imposed by the new technology. PMID- 1458758 TI - Clinical decision making in intracranial aneurysms and aneurysmal subarachnoid hemorrhage--science and art. PMID- 1458759 TI - (Honored guest lecture) intracranial arteriovenous malformations. PMID- 1458760 TI - The role of pharmacokinetics in the development of biotechnologically derived agents. PMID- 1458761 TI - Clinical pharmacokinetics of ketorolac tromethamine. AB - Ketorolac is a new chiral nonsteroidal anti-inflammatory drug (NSAID) which is marketed for analgesia as the racemate. The drug is administered as the water soluble tromethamine salt and is available in tablets or as an intramuscular injection. The absorption of ketorolac is rapid, Cmax being attained between 20 to 60 min. Its oral bioavailability is estimated to range from 80 to 100%. The drug is extensively bound (> 99%) to plasma proteins and has a volume of distribution (0.1 to 0.3 L/kg) comparable with those of other NSAIDs. Only small concentrations of ketorolac are detectable in umbilical vein blood after administration to women in labour. The elimination half-life is between 4 and 6h and is moderate in comparison with other NSAIDs. The area under the plasma concentration-time curve of ketorolac is proportional to the dose after intramuscular administration of therapeutic doses to young healthy volunteers. Ketorolac is extensively metabolised through glucuronidation and oxidation; little if any drug is eliminated unchanged. Most of the dose of ketorolac is recovered in the urine as conjugated drug. Although ketorolac is excreted into the breast milk, the amount of drug transferred comprises only a small fraction of the maternal exposure. Little stereoselectivity was present in the pharmacokinetics of ketorolac in a healthy volunteer receiving single intravenous or oral doses. The elderly exhibit reduced clearance of the drug. Renal insufficiency appears to cause an accumulation of ketorolac in plasma, although hepatic disease may not affect the pharmacokinetics. PMID- 1458762 TI - Pharmacodynamic monitoring of cyclosporin. AB - The efficacy of cyclosporin as an immunosuppressive agent is largely based on clinical indicators such as graft survival, rejection or nephrotoxicity. Therapeutic monitoring is necessary to evaluate the efficacy of cyclosporin therapy. The most widely used method for monitoring cyclosporin therapy is the measurement of predose through blood concentrations of the drug. The relationship of a single or multiple blood cyclosporin concentration to slowly evolving outcomes is difficult to establish. Some investigators have found a good correlation between cyclosporin trough concentrations on the one hand and cyclosporin toxicity and rejection on the other, but others have not. Therapeutic monitoring of cyclosporin may be enhanced using some biological assays for immunosuppression (pharmacodynamic monitoring) in addition to cyclosporin trough concentrations (pharmacokinetic monitoring). However, direct monitoring of the immune response to cyclosporin therapy using a clinically applicable biological assay is difficult. Some pharmacodynamic parameters have been suggested as biological markers in the clinical monitoring of cyclosporin. PMID- 1458764 TI - Pharmacokinetic study of omeprazole in elderly healthy volunteers. AB - The pharmacokinetics of omeprazole and its metabolites were studied in 8 healthy elderly volunteers using [14C]omeprazole. In another 6 healthy elderly volunteers, the pharmacokinetics of omeprazole were studied using unlabelled drug. Each volunteer received single doses of omeprazole intravenously (20mg) and orally (40mg) as solutions in a randomized crossover design. The plasma concentrations and urinary excretion of omeprazole and metabolites were followed for 24 and 96h, respectively. The results indicate that the average metabolic capacity of omeprazole is decreased in the elderly compared with that found in earlier studies of healthy young individuals. This was reflected in an increase in bioavailability from 56 to 76%, a reduction in mean systemic clearance by approximately 50% (0.25 L/min) and a prolongation of the mean elimination half life from 0.7 to 1.0h compared with the young. Despite these findings, the considerable overlap in these parameters between young and old volunteers, together with data from previous pharmacodynamic studies and the wide therapeutic range of omeprazole, indicate that dosage reductions are not needed in the elderly. PMID- 1458765 TI - Lack of pharmacokinetic interactions between moxonidine and digoxin. AB - The potential for pharmacokinetic interactions between moxonidine and digoxin at steady-state was investigated in 15 healthy male volunteers. Multiple oral doses of 0.2mg moxonidine twice daily and 0.2mg digoxin once daily were administered alone and in combination in a randomised 3-period crossover design. The drugs were administered for at least 5 days. The results indicate that neither moxonidine nor digoxin influences the pharmacokinetics of the other drug under steady-state conditions. PMID- 1458766 TI - The clinical value of FDA class C drugs approved from 1981 to 1988. PMID- 1458767 TI - Endothelin-I-mediated vasoconstriction: specific blockade by verapamil. AB - The capacity of three vasodilators that act by distinct mechanisms to reverse endothelin-I-mediated vasoconstriction was studied in 11 healthy nonsmoking male subjects (mean age +/- SEM, 26 +/- 2 years; mean weight +/- SEM, 74 +/- 2 kg) by use of brachial artery infusion and forearm strain-gauge plethysmography. Isoproterenol (cyclic adenosine monophosphate-mediated vasodilation), sodium nitroprusside (cyclic guanosine monophosphate-mediated vasodilation), and verapamil (L-type calcium channel blocker) were compared for capacity to reverse endothelin-I-mediated increase in forearm vascular resistance (FVR). Endothelin-I infusion increased FVR 1.9-fold in the control state. Isoproterenol infusion decreased FVR with or without concurrent endothelin-I infusion; however, at comparable isoproterenol infusion rates, endothelin-I increased FVR similar to the control state (for 5 ng/min isoproterenol, endothelin-I increased FVR 1.85 fold; for 12.5 ng/min isoproterenol, endothelin-I increased FVR 2.03-fold). Similarly, sodium nitroprusside infusion decreased FVR with or without concurrent endothelin-I infusion; however, at comparable sodium nitroprusside infusion rates the endothelin-I increase in FVR was similar to control (for 0.48 micrograms/min sodium nitroprusside, endothelin-I increased FVR 1.89-fold; for 0.96 micrograms/min sodium nitroprusside, endothelin-I increased FVR 2.36-fold). In contrast, verapamil infusion decreased FVR with or without endothelin-I infusion. At a verapamil infusion rate of 19.1 microns/min, endothelin-I increase in FVR was comparable to control (for 19.1 microns/min verapamil, endothelin-I increased FVR 1.36-fold, less than the 1.0-fold increase in the control state; p < 0.05). Isoproterenol and sodium nitroprusside decreased FVR during concurrent endothelin I infusion but did not reverse the endothelin-I effect. In contrast, verapamil reversed endothelin-I--induced vasoconstriction to control FVR, suggesting a specific antagonism of endothelin-I--mediated increase in FVR. PMID- 1458763 TI - Methods of determining plasma and tissue binding of drugs. Pharmacokinetic consequences. AB - The available techniques for the investigation of drug binding to plasma and tissues protein are reviewed and the advantages and disadvantages of the various techniques stated. A comparison of different plasma protein binding techniques is made which shows that the size of the unbound fraction of drug may be influenced by the method used. Protein binding may be assayed by methods including equilibrium dialysis, ultrafiltration, ultracentrifugation, gel filtration, binding to albumin microspheres and circular dichroism. Tissue binding techniques can involve testing binding to isolated organs, tissue slices, homogenates and isolated subcellular particles. Details of the available methods to compute pharmacokinetic constants are given. Stereoselective binding has been investigated for a limited number of drugs and the difference in the binding of 2 enantiomers is usually modest. The measurement of the binding constants is often required to characterise the drug-protein interaction. Mathematical and graphical methods to compute the pharmacokinetic parameters are discussed. The implications of binding on the volume of distribution and clearance of drugs are examined. PMID- 1458768 TI - Comparison of vasodilatory responses to nitroglycerin and its dinitrate metabolites in human veins. AB - Independent of the route of nitroglycerin administration, substantial amounts of 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3-GDN) metabolites accumulate in humans. Thus far their pharmacologic activity in comparison to nitroglycerin in humans is unknown. To compare the venodilatory potency of nitroglycerin and of 1,2-GDN and 1,3-GDN in vivo, cumulative dose-response curves were established in nine healthy volunteers by use of the dorsal hand vein compliance technique. Separated by a washout period, two of the three venodilators were infused in randomized order after preconstriction with phenylephrine. Values for maximum vasodilation were similar for all compounds: nitroglycerin, 109%; 1,2-GDN, 100%; and 1,3-GDN, 106%. The respective values for the dose rate exerting 50% of maximum vasodilation were 5.1, 43, and 60 ng/min, indicating that the dinitrates were about 10 times less potent than nitroglycerin (p < 0.001) but not significantly different from each other. The findings support the hypothesis that activity of nitroglycerin metabolites is related to the number of nitrate groups in the molecule and are in agreement with lower dinitrate potencies found in animal experiments. PMID- 1458769 TI - Pharmacokinetics and biochemical efficacy of pirmagrel, a thromboxane synthase inhibitor, in renal allograft recipients. AB - The effects of a 48-hour 0.5 mg/kg/hr infusion of the thromboxane synthase inhibitor pirmagrel were studied in 10 renal allograft recipients with cyclosporine nephrotoxicity. Plasma concentrations reached a mean steady-state plasma level of 1798 +/- 481 ng/ml. Biphasic, rapid elimination of pirmagrel was observed with a distribution half-life of 6.7 minutes and a terminal half-life of 73 minutes. Plasma clearance and the volume of distribution of the drug were 300 +/- 87 ml/hr/kg and 497 +/- 232 ml/kg, respectively. The pharmacodynamic effects of pirmagrel were marked by a mean 96% suppression of serum thromboxane B2 (TXB2), which coincided with a suppression of urinary excretion of TXB2, 2,3 dinor-TXB2, and 11-dehydro-TXB2 of 85% +/- 8%, 91% +/- 5%, and 89% +/- 9%, respectively. Urinary excretion of all thromboxane metabolites measured at the end of 1 week after termination of infusion was returned to the baseline. In conclusion, pirmagrel caused effective and sustained suppression of all thromboxane derived metabolites in plasma and urine during continuous infusion in kidney transplant patients receiving cyclosporine. PMID- 1458770 TI - Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers. AB - STUDY OBJECTIVE: The study was performed to evaluate the relative sensitivity of various noninvasive methods to detect and describe the systolic cardiovascular effects of stepwise increasing doses of isoproterenol: two-dimensional left ventricular echocardiography (main variable, ejection fraction), ACVF (attenuation compensated volume flow)--dual-beam Doppler echoaortography (time averaged mean velocity), electrical impedance cardiography [(dZ/dtmax)/RZ index], and systolic time intervals from mechanocardiography (PEP and QS2c). METHODS: Isoproterenol was administered by constant rate intravenous infusion in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 minutes). Saline control infusions were given in analog fashion. The treatments (isoproterenol and saline solution) were administered in a period-balanced two way crossover design with randomly allocated sequences. The subjects, observers, and analysts were blinded to the treatment protocol. Study subjects were 10 healthy male volunteers (age range, 23 to 31 years; mean age, 26.6 years). RESULTS: Compared with saline solution, isoproterenol caused a dose-related increase in ejection fraction, (dz/dt)/RZ index, and time-averaged mean velocity and a dose-related shortening of PEP and QS2c. The responses are congruent with an enhancement of cardiac systolic performance caused by a positive inotropic stimulation and an afterload reduction ("inodilatory" response). The effects on systolic time intervals reached statistical significance (alpha = 0.05) at the first isoproterenol dose step, the effects on the impedance cardiography and the Doppler echoaortography variables reached statistical significance at the second dose step, and the effects on the two-dimensional echocardiography reached statistical significance at the third dose step. CONCLUSIONS: All methods allowed to detect isoproterenol-related changes. Systolic time intervals were the most sensitive, followed by impedance cardiography, ACVF--dual-beam Doppler echoaortography, and two-dimensional echocardiography. The practical convenience and high sensitivity of the systolic time intervals makes them suitable to evaluate investigational systolic inodilatory changes in humans. PMID- 1458771 TI - Effects of bezafibrate on insulin sensitivity and glucose tolerance in subjects with combined hyperlipidemia. AB - To investigate whether the lowering of triglyceride levels has beneficial effects on glucose metabolism, we studied 13 nondiabetic men with combined hyperlipidemia (phenotype IIB) before and after 2 months of treatment with a slow-release formulation of bezafibrate (400 mg daily). The rates of whole body glucose disposal were quantitated by the euglycemic hyperinsulinemic clamp technique (insulin infusion rate of 80 mU/m2/min). In an oral glucose tolerance test, fasting glucose level decreased slightly (5.0 +/- 0.2 versus 4.8 +/- 0.2 mmol/L; p < 0.05) during bezafibrate treatment. Glucose and insulin levels after an oral glucose load remained unchanged. Rates of whole body glucose disposal did not change during bezafibrate treatment (39.5 +/- 3.3 mumol/kg/min before treatment versus 40.6 +/- 2.7 mumol/kg/min after treatment; difference not significant). Basal hepatic glucose output also remained unchanged (8.2 +/- 0.2 mumol/kg/min before treatment versus 8.3 +/- 0.2 mumol/kg/min after treatment; difference not significant). Our findings show that bezafibrate has a triglyceride-lowering effect without any significant influence on insulin sensitivity. PMID- 1458772 TI - Nasal spray nicotine replacement suppresses cigarette smoking desire and behavior. AB - The effects of short-term nasal spray nicotine replacement in suppressing desire to smoke and ad libitum cigarette smoking behavior were evaluated in male and female smokers. In study I, 10 male and 10 female smokers received intermittent doses of 0, 7.5, 15, and 30 micrograms/kg nicotine by way of measured-dose nasal spray, with each dose on a separate day. Self-reported desire to smoke was significantly suppressed by each nicotine dose compared with placebo, but there were no significant differences among nicotine doses or between men and women. In study II, eight male and eight female smokers received 0, 15, and 30 micrograms/kg nicotine intermittently and were allowed to smoke their preferred brands of cigarettes ad libitum. Similar to study I, nicotine replacement significantly suppressed number of cigarettes smoked, number of puffs, and carbon monoxide boost and increased latency to smoking, but there were almost no significant differences between the two nicotine doses. Magnitude of smoking suppression attributable to 15 micrograms/kg tended to be greater in men than in women. However, plasma nicotine concentrations were significantly higher after 15 and 30 micrograms/kg versus placebo, suggesting only partial compensation in smoking behavior with short-term nasal nicotine replacement. These findings support the idea that short-term nicotine replacement decreases smoking desire and behavior, but the findings indicate that smoking behavior is partly influenced by factors other than nicotine regulation. PMID- 1458773 TI - Racial and gender differences in N-acetyltransferase, xanthine oxidase, and CYP1A2 activities. AB - BACKGROUND: The urinary molar concentration ratios of several caffeine metabolites are indicators of specific drug metabolizing enzyme activities. The ratios of 5-acetyl-amino-6-formylamino-3-methyluracil (AFMU) to 1-methylxanthine (1X), AFMU to 1X plus 1-methyluric acid (1U), and AFMU to 1X + 1U + AFMU are indicative of N-acetyltransferase (NAT) activity; the ratios of 1U to 1X and 1U to 1U + 1X indicate xanthine oxidase activity; and the ratio of the sum of 7 demethylated metabolites (AFMU + 1X + 1U) to the precursor for all three compounds, paraxanthine (PX), is a putative indicator of CYP1A2 oxidative activity. Our objective was to discern whether there are race-, gender-, and age related differences in these indexes of drug-metabolizing activity. METHODS: In 342 normal healthy unrelated subjects, metabolites were measured in urine collected after administration of low-dose caffeine. RESULTS: By two-way analysis of variance, NAT activity was higher in black subjects than in white subjects when assessed as AFMU/(1U + 1X) or as AFMU/(AFMU + 1U + 1X) (p = 0.001 and p = 0.002, respectively), but less so by use of AFMU/1X (p = 0.08). Xanthine oxidase activity, as assessed by 1U/1X or as 1U/(1U + 1X), was lower in black subjects than in white subjects (p = 0.02 and p = 0.001, respectively) and was lower in males than in females (p = 0.001 for both ratios). Females had higher AFMU/1X ratios (p = 0.03) because of higher xanthine oxidase activity. In a model in which AFMU/1X was the dependent variable and race, sex, age, and an index of xanthine oxidase (1U/1X) were independent variables, only race and 1U/1X were significant determinants of this NAT index (p = 0.003 and p < 0.001, respectively). The CYP1A2 ratio was lower in black subjects (p = 0.036) and in females (p = 0.015). CONCLUSION: Racial and gender differences in xanthine oxidase activity render the AFMU/1X ratio less reliable as an assessment of NAT activity in a heterogeneous population compared with the AFMU/(1U + 1X) or AFMU/(AFMU + 1U + 1X) ratios. The observed racial and gender differences in NAT, xanthine oxidase, and CYP1A2 activities may have implications for racial and gender differences in drug effects and carcinogen biotransformation. PMID- 1458774 TI - Activity of oxidative routes of metabolism of debrisoquin, mephenytoin, and dapsone is unrelated to the pathogenesis of vinyl chloride-induced disease. AB - The hypothesis, that cytochrome P4502D6, cytochrome P4502CMP, cytochrome P4503A4 or N-acetyl-transferase may form active intermediary metabolites that could be etiologically related to vinyl chloride-induced disease was investigated in 21 drug-free workers with previous development of vinyl chloride-induced disease and in 23 drug-free workers from the same plant who did not develop the syndrome. Each subject received simultaneous oral administration of debrisoquin (10 mg), mephenytoin (100 mg), and dapsone (100 mg). Measurement of the debrisoquin recovery ratio, the 8-hour recovery of 4-hydroxymephenytoin, and the dapsone recovery ratio in the subsequent 8-hour urine sample provided in vivo phenotypic indexes of cytochromes P4502D6, P4502CMP, and P4503A4 activity, respectively. An 8-hour blood sample was used to measure the acetylation ratio, a measure of N acetyltransferase activity. The frequency distributions of each drug metabolizing activity were similar between groups. Within this small sample, there was no evidence to implicate cytochromes P4502D6, P4502CMP, and P4503A4 and N acetyltransferase in the pathogenesis of vinyl chloride-induced disease. PMID- 1458775 TI - Translocation (8;12)(q13;q15) in a pediatric tumour. AB - A reciprocal translocation, t(8;12)(q13;q15), was found to be the sole karyotypic change in a deep-seated lipogenic tumour in a 3-year-old child. Judging from recent data on the cytogenetic characterization of adipose tumours, this finding seems to support the histopathologic diagnosis of lipoma in spite of foci of atypical cells observed at the histologic examination. PMID- 1458776 TI - IgD serum levels are influenced by HLA-DR phenotype. AB - In the present paper we have evaluated IgD serum levels of 84 randomly selected HLA-typed healthy Sicilians. The values were analysed according to age, sex and HLA-DR phenotypes. No correlation between age and IgD serum levels was found in our population since all subjects were in a narrow age range. Furthermore, no significant association was found between IgD serum levels and gender of studied subjects. The evaluation of IgD serum levels according to HLA-DR phenotypes revealed that HLA-DR1 positive subjects displayed significantly higher values. These results are in agreement with previous reports showing that HLA phenotypes may be involved in the control of serum immunoglobulin levels. Furthermore, present data strengthen our suggestion that HLA-DR1 phenotype is related to the 'high responder' immunological profile. PMID- 1458777 TI - Coefficients of relationship by isonymy among Scottish males with early and late onset cancers. AB - Studies of certain cancers suggest that early onset cases tend to have a more pronounced hereditary component than late onset cases. We have analysed data from 60,924 Scottish males with cancer of the stomach, colon, rectum, prostate or bladder, using the coefficient of relationship by isonymy to compare patients whose age at registration was below the median with those whose age at registration was equal to or above the median. There was no evidence for greater isonymy in younger patients suggesting that, although known genetically determined cancers may have earlier onset than other cancers at the same site, early age at onset is not widely associated with a familial predisposition to malignancy. PMID- 1458778 TI - Phenotypic markers for functional lymphocyte populations: a critical appraisal of current usage as disease markers and future prospects. AB - Abnormal immune function plays a role in a number of diseases, and measurement of immune function is an important role for Clinical Immunology laboratories (Chapel and Sewell, 1990; Miller et al., 1991; Rose et al., 1986; Stites, 1991). Tests for lymphocyte function tend to be slow and tedious, and to lack clinically useful discriminatory power; as a result their use in a clinical context is limited (see references cited above). On the other hand, the increasing numbers of monoclonal antibodies against lymphocyte membrane molecules has led to the use of markers as indicators of functional potential (Reinherz and Schlossman, 1982). This review examines the characteristics that make a clinically useful panel of markers, considers the kinds of questions that can be answered by marker or in vitro functional studies, reviews markers and functional assays in current use and proposes a panel of markers that may be worthy of further evaluation. PMID- 1458779 TI - Lymphocyte surface phenotype in common variable immunodeficiency. PMID- 1458780 TI - Karel Capek--Czech writer, sufferer from ankylosing spondylitis. PMID- 1458782 TI - Bacterial arthritis in a district hospital. AB - Between 1977 and 1988 in the Enschede hospital 72 patients were seen with bacterial arthritis of one or more joints. Staphylococcus aureus was most frequently the causative agent (52%) and the knee was the most frequently infected joint (42%); the mortality rate was 11%. Complete restoration of pre existent function was seen in 52% of the affected joints. In patients with severe deterioration of joint function after the bacterial infection, the period between the first symptoms and start of treatment (mean 30 days) was significantly longer than in patients with no or moderately deteriorated joint function (mean 10 days). The primary focus was mostly a skin infection, predominantly localized on the lower extremities. Half of all cases of bacterial arthritis occurred in patients with rheumatoid arthritis (RA). We therefore conclude that patients with RA and skin infections, especially if localized on legs or feet, should be treated without delay and that one should not hesitate to prescribe antibiotics. Erythrocyte sedimentation rate (ESR) was less than 20 mm after one hour in 13% and blood leucocyte count less than 10 x 10(9)/liter in 55% of all patients, showing that a normal ESR and/or blood leucocyte count do not exclude bacterial arthritis. In 4 out of 9 patients with infected prosthetic joints the infection resulted in loosening of the joint, before antibiotic treatment was started. In the other 5 patients bacterial arthritis recurred, in one patient resulting in loosening of the joint, only shortly after stopping long-term successful antibiotic treatment (6-24 months). Thus, we feel that lifelong treatment with antibiotics is a reasonable alternative in cases, where the risk of surgery is very high. PMID- 1458781 TI - Anti-dsDNA and Sm autoantibodies in systemic lupus erythematosus. AB - During the present study the coincidence of anti-dsDNA and Sm antibodies was detected in 16 percent of 51 consecutive SLE patients. These antibodies were detected by the standard indirect immunofluorescence and Ouchterlony tests. All patients with anti-dsDNA and Sm antibodies showed disease activity, including renal, CNS and pulmonary disease. We excluded a cross reactivity of these antibodies by ELISA, using competitive experiments with dsDNA and Sm antigens. The results support the presence of multiple autoantibody production during SLE activity, and suggest that different mechanisms may underlie the induction and regulation of both autoantibodies. PMID- 1458783 TI - Long-term follow-up study of 164 patients with definite systemic sclerosis: classification considerations. AB - To evaluate the usefulness of recently proposed schemes of classification for systemic sclerosis an extensive cross-sectional study of a series of 164 consecutive patients with long-term systemic sclerosis was undertaken. There were 47 cases of proximal sclerosis, 93 of distal sclerosis and 24 of complete CREST syndrome. The study included clinical, visceral, immunological and follow-up data. In addition, a quantitative clinical score was calculated for each patient, thus providing indications for prognosis. Data were expressed according to three conventional systems of classification: The ARA system, the diffuse versus limited systemic sclerosis system and the early cutaneous involvement system. The most reliable indications of severe outcome were: proximal sclerosis, trunk skin involvement, presence of anti Scl 70 autoantibody, pulmonary and/or heart involvement and age. Diagnosis and prognosis were not generated by the same items. Prognosis indicators proved more accurate for groups than for individuals. Mortality was 1 death per 149 patient X years of follow-up from diagnosis. We conclude that the ARA criteria for classification should be recognized as a standard, but patients with complete CREST syndrome should be included in the distal group. Other systems of classification, principally 2-way versus 3-way criteria, allow different subsets of patients that correlate with prognosis and the severity of the disease, and could be used for therapeutic purposes. PMID- 1458784 TI - Noninfectious osteitis: part of the SAPHO syndrome. AB - SAPHO, a rare syndrome, is a recently suggested acronym for synovitis, acne, pustulosis, hyperostosis and osteitis. It encompasses many features which have been described in different but overlapping conditions. Not all of the syndrome components need to be present for inclusion in SAPHO to be justified, especially the dermatologic components. Two cases are described as examples. Clinicians should be aware of this rare disorder if positive early diagnoses are to be made in patients presenting with skeletal pain. PMID- 1458785 TI - Radiographic findings of spontaneous subluxation of the sternoclavicular joint. AB - Eight middle-aged women with spontaneous atraumatic subluxation of the sternoclavicular joint were evaluated with radiography and computed tomography. All patients were employed in occupations involving moderate to heavy physical labour, and no patients could recall a specific traumatic incident associated with onset of symptoms. In seven of the eight patients, the displacement of the medial clavicle was in a cranial direction; in four of the eight patients, there was an associated anterior subluxation, and in one patient, the subluxation was purely anterior. All five patients with an anterior component to the sternoclavicular subluxation had associated condensing osteitis of the clavicle. The sclerosis of the medial clavicle is possibly the result of chronic abrasion on the sternum and first costal cartilage in association with normal respiration and with upper extremity motion. PMID- 1458786 TI - Thermography of frozen shoulder and rotator cuff tendinitis. AB - The role of thermography in the diagnosis of soft tissue lesions of the shoulder was evaluated by screening 28 patients with unilateral frozen shoulder and 86 patients with unilateral rotator cuff lesions. Index shoulders were then compared with the normal side. Differences in skin temperature distribution were found in 82% of subjects with frozen shoulder, nearly three-quarters of whom had reduced skin temperature. There was no consistent pattern of shoulder skin temperature found in rotator cuff tendinitis patients (49% normal, 28% reduced, 23% increased). Thermography can be helpful in the diagnosis of frozen shoulder but further studies are required to determine whether it is useful in other soft tissue shoulder lesions. PMID- 1458787 TI - Clinical differences between ANA/anti-ENA positive or negative primary Sjogren's syndrome. AB - Fifty female patients with primary Sjogren's syndrome diagnosed according to the Copenhagen criteria were evaluated for both glandular and extraglandular involvement. They were divided into two groups based on the presence or absence of antinuclear and anti-ENA antibodies (ANA/anti-ENA). ANA/anti-ENA negative patients presented with milder and later glandular and extraglandular disease and required less frequent corticosteroid treatment. No significant differences were noted in extraglandular manifestations with the exception of leukopenia which was noted only in ANA/anti-ENA positive cases. PMID- 1458788 TI - Effects of different regimes of corticosteroid treatment on calcium and bone metabolism in rheumatoid arthritis. AB - A clinical study of 30 patients with rheumatoid arthritis was undertaken in order to assess the acute effects of corticosteroids on calcium and bone metabolism. The patients were randomly divided into 3 groups. The first group was not treated with corticosteroids, the second group was treated with 3 oral pulses of 100 mg prednisolone and the third group received 3 intravenous pulses of 1000 mg methylprednisolone (MP) on alternate days during one week. In both steroid treated groups the serum parathyroid hormone concentration tended to increase. In the MP treated group an increase in the 1,25-dihydroxyvitamin D concentration after the first pulse was followed by a significant drop; this effect was also seen, but somewhat retarded and less distinct, in the orally treated group. In the MP treated group the urinary calcium excretion raised significantly 6 hrs after the first pulse and then dropped significantly. In all groups no changes were found in the serum calcium level and the urinary excretion of hydroxyproline. We conclude that, acute changes in calcium and bone metabolism occur during treatment with intravenous pulses of methylprednisolone and with oral pulses of prednisolone. These changes are small and reversible in a few days. PMID- 1458789 TI - Decreased interleukin-1 beta levels in plasma from rheumatoid arthritis patients after dietary supplementation with n-3 polyunsaturated fatty acids. AB - The effects of dietary supplementation with n-3 fatty acids on the level of cytokines and complement activation in plasma from patients with rheumatoid arthritis were examined. Thirty-two patients with active rheumatoid arthritis were included in a 12-week double-blind, randomized study of dietary supplementation with n-3 fatty acids (3.6 g per day) or placebo. The cytokines were measured in plasma before and after treatment with fish oil or placebo. In general, cytokine values at the upper limits of the calculated normal areas were found. The Interleukin-1 beta concentration in plasma was reduced significantly after 12 weeks of dietary supplementation with fish oil (p < 0.03). No significant difference was observed in the placebo group. The tumour necrosis factor alpha activity in plasma did not change significantly (p = 0.167). No significant changes were observed in the degree of complement activation. The clinical status of the patients was improved in the fish oil group, but not in the placebo group, judged by Ritchie's articular index (p < 0.02). We conclude that dietary supplementation with n-3 fatty acids results in significantly reduced plasma IL-1 beta levels in patients with rheumatoid arthritis. Even though the cytokine levels were low, the anti-inflammatory effect of n-3 fatty acids could in part be explained by their ability to decrease cytokine production. PMID- 1458790 TI - Rheumatoid nodulosis: a puzzling variant of rheumatoid arthritis. AB - Four patients with rheumatoid nodulosis are here described, together with a review of cases reported to date in the literature. This particular variant of rheumatoid arthritis (RA) is characterized by the presence of subcutaneous rheumatoid nodules, scanty or absent systemic manifestations and a clinically benign course. Joint involvement appears more commonly as palindromic rheumatism, although patients with arthralgia episodes alone and others with chronic polyarthritis have been described. Seldom reported up to now, a consideration of this entity may help to avoid diagnostic pitfalls and the use of aggressive therapy. PMID- 1458791 TI - Vestibular syndrome in multiple myeloma: role of magnetic resonance imaging. AB - The authors report a case of multiple myeloma involving the temporal bone and responsible for a vestibular syndrome associated with hypoacusis. The lesion was best visualised by magnetic resonance imaging. PMID- 1458792 TI - Possible causal association between ulcerative colitis and idiopathic thrombocytopenic purpura. AB - A 24-year-old Japanese male having ulcerative colitis and idiopathic thrombocytopenic purpura is described. When the symptoms of ulcerative colitis were manifest during his clinical course, the platelet life-span was shortened and the platelet associated IgG level was increased. Thus, causal association between the two diseases may be suggested. PMID- 1458793 TI - A case of Raynaud's disease with uterine cancer producing interleukin-6. AB - A case of cervical cancer of the uterine producing interleukin-6(IL-6) in a patient who suffered from Raynaud's phenomenon is described. Her serum contained anti SS-A antibody. The cancer was removed surgically. High level of IL-6 activity was detected in the culture supernatant of the resected cancer cells. After operation, Raynaud's phenomenon had improved and anti SS-A antibody had disappeared. This case shows us that IL-6 produced by malignant tumour might induce autoimmune connective tissue disease-like symptoms. PMID- 1458794 TI - Recurrent and migratory reflex sympathetic dystrophy syndrome. AB - A case of recurrent reflex sympathetic dystrophy syndrome (RSDS), involving consecutively three extremities in an otherwise healthy adult is described. In a period of four years follow-up she presented three RSDS episodes occurring without precipitating events and involving consecutively both lower legs and the left hand. The RSDS resolved without sequelae after treatment with physiotherapy and diclofenac in an early phase. RSDS is an often unrecognized entity which appears mostly confined to a single limb. Recurrent forms have also been described, sometimes with a migratory pattern. Involvement of upper and lower limbs in the same patient is thought to be infrequent. PMID- 1458795 TI - Behcet's syndrome and factor XII deficiency. AB - Several mechanisms have been proposed to explain thrombotic tendency in Behcet's syndrome. We report the case of a 43-year old woman presenting retinal-vein thrombosis, factor XII deficiency and Behcet's syndrome. This kind of association has thus far never been reported. Factor XII deficiency is known to possibly induce various types of thrombosis and might explain the prevalence of ocular symptoms in our patient. PMID- 1458796 TI - Bacterial pyomyositis in a patient with a multiple myeloma. AB - Pyomyositis is relatively rare in regions with a temperate climate. The most common aetiologic agent is staphylococcus aureus. Most patients with pyomyositis from temperate regions involve immunocompromised states. Because of the rarity, it is often initially misdiagnosed. Computed tomography scan is considered the most helpful tool for the diagnosis of pyomyositis. We present a case in a patient with multiple myeloma. PMID- 1458797 TI - Localized nodular myositis. A paraneoplastic phenomenon. AB - Localized nodular myositis was recognized in an elderly man six months prior to the diagnosis of Hodgkin's disease. Meticulous search of the muscle specimen failed to disclose tumorous involvement. The possible paraneoplastic nature of localized nodular myositis in this patient is discussed. PMID- 1458798 TI - Rheumatoid arthritis, corticosteroid therapy and Kaposi's sarcoma: a coincidence? A case and review of literature. AB - We describe a 68-year-old woman suffering from rheumatoid arthritis treated with low doses of prednisone who developed Kaposi's sarcoma (KS). This patient was not affected with AIDS, and two years previously, her sister had also complained of KS. In the literature only 8 rheumatoid arthritis patients who developed KS during steroid therapy have been reported. We present a review of the literature and question the responsibility of corticosteroids and autoimmune diseases as the cause of KS. PMID- 1458799 TI - Ankylosing spondylitis and sarcoidosis--coincidence or association? Case report and review of the literature. AB - We report a 25-year-old woman presenting with sarcoidosis and bilateral sacroiliitis. Her sarcoidosis related symptoms (malaise, cough and dyspnoea) improved dramatically under treatment with steroids but severe back pain persisted. Only seven similar cases have been described over the last 40 years and the question of a possible association between the two diseases has been raised. However, prevalence data from the literature and the apparent lack of genetic links are better arguments for coincidence than for association. PMID- 1458800 TI - Radiological vignette. Insufficiency fracture of the acetabulum. AB - An insufficiency fracture (IF) involving the acetabulum is presented. This fracture occurred in a 67-year-old woman who had been hysterectomized and oophorectomized 27 years earlier for a carcinoma of the uterine cervix, and who had received external pelvic irradiation. This IF location has been rarely described earlier, and its awareness should preclude unnecessary aggressive diagnostic procedures especially in patients with osteoporosis and previous pelvic radiotherapy. PMID- 1458801 TI - Avascular necrosis of bone in systemic sclerosis. PMID- 1458802 TI - Bone manifestations associated with AIDS. PMID- 1458803 TI - [An open non-comparative study of the efficacy and tolerability of sultamicillin in the therapy of respiratory infections in childhood]. AB - Forty-eight children (25 males + 23 females), mean age 3.5 years +/- 2.6 (range 1 11), were treated for the following respiratory infections: pharyngotonsillitis (9), bronchitis (18), bronchopneumonia (14), asthmatic bronchitis (4) and pneumonia (3). The average duration of treatment was 5.3 +/- 2.0 days (range 3 13). Sultamicillin was administered at the dose of 50 mg/kg/day. Patients with fever experienced a defervescence on the second day of therapy. Forty-six children (96%) showed a good clinical response. The tolerability of the drug was excellent or good in 93.8% of the cases. PMID- 1458804 TI - [Ocular pathology in HIV infection]. AB - The above short note underscores the importance of ocular complications in HIV infection. These syndromes are either isolated or concomitant with CNS involvement but frequently they do not receive due consideration. PMID- 1458805 TI - [Telethermography in the diagnosis of lumbo-sciatica syndromes]. AB - Thermal maps of the lumbo-sacral and gluteal regions and of the lower limbs were obtained with telethermography in 30 subjects suffering from painful lumbo sciatic syndromes in order to assess whether there were differences of thermal index between painful and opposite side, and to evaluate the telethermographic patterns of the irritative and deficitary forms. Among 25 patients with lumbo sciatalgia in the irritative or early stage, 16 showed hypothermia of the affected side; in three of the five patients in the deficitary stage, hyperthermia of the affected side was observed while two did not show changes of the thermal gradient. The authors stress the importance of telethermography and suggest that this method, which is not costly, non-invasive and easily reproducible, should be used to complete diagnosis of and to monitor lumbo sciatalgic syndromes. PMID- 1458806 TI - [Efficacy and tolerability of ketoprofen lysine salt foam for topical use in the treatment of traumatic pathologies of the locomotor apparatus]. AB - In this study the authors evaluated the efficacy and tolerability of a foam of 15% ketoprofen lysine salt versus placebo in patients with articular traumas, pains and strains, distortions etc. All parameters considered were statistically significantly decreased after 7 days of active treatment as compared to placebo. Pain score decreased significantly at pressure (p < 0.001), pain on active movement (p < 0.005), pain on passive movement and pain at rest. Efficacy of the active foam was graded as satisfactory in 81.7% and its tolerability in 92.7% versus 44% and 29% with placebo respectively. Patients reported high acceptability (89%) of the new foam formulation. No systemic or local side effects were observed or reported. The 15% ketoprofen lysine salt foam for topical use can be considered an effective antiinflammatory and analgesic drug for the treatment of minor orthopedic and traumatic disorders, and was found to be perfectly tolerated. PMID- 1458807 TI - [Recent experience in the short-term etizolam treatment of irritable colon syndrome]. AB - Twenty-two subjects (8 males, 14 females, mean age 36 years, range 21-57) with symptoms of diffuse pain or fullness in a lower abdominal quadrant, without repercussions on general health but with chronic anxiety of which the subjects complained or which emerged during confidential conversation with the physicians, were enrolled in our outpatient department for liver and gastroenterologic pathology at the Institute of Internal Medicine and Metabolic Disorders, II Faculty of Medicine, Naples University. After an average 30-day wash-out period, patients were treated with etizolam, a new psychoactive drug for somatized anxiety. Mean dosage and duration of treatment were 1 tablet twice daily for 25 days. Painful symptoms disappeared in 16.3% of patients, decreased in 38.3% and remained stationary in 22.7% and became worse in 22.7%. Number of bowel motions decreased in 14 patients (63.6%, from an average of 2.04 to 1.56). It can therefore be concluded that etizolam treatment was effective in subjects with colon disorders accompanied by chronic anxiety syndrome or that became acute as result of stressful socio-economic or affective situations or personal disappointment. PMID- 1458808 TI - [Silent myocardial ischemia with raised ST tract in 2 octogenarian patients without ischemic cardiopathy]. AB - The authors describe two recently observed cases of silent angina with ST segment elevation. The patients, both 80-years old, were submitted to 24-hour Holter examination to account for recurrent episodes of dizziness. The examination revealed silent angina with ST elevation concentrated mainly in the late evening and morning hours, accompanied by accelerated heart rate. Treatment with low diltiazem doses was completely successful. PMID- 1458809 TI - [Role of magnetic resonance in the evaluation of thrombosis of large thoraco abdominal vessels]. AB - Magnetic resonance (MR) has been found to be a method suitable for the study of the vascular system since it permits to distinguish between moving (circulating blood) and static (thrombi, atherosclerotic plaques, intimal flaps) tissues. The sequences used for the evaluation of thrombi are Spin Echo (SE) and Gradient Echo (GE). If both sequences are used the diagnosis of thrombosis is considerably more reliable. The limits of the technique are represented by spatial resolution which is not optimal and makes the evaluation of thrombi in small or medium-size vessels difficult; further, small or non occlusive thrombi may be difficult to identify. Nowadays, with the technique of angiography with magnetic resonance (AMR) it has become possible to obtain high quality images of the vessels of the head, neck, abdomen and limbs. Further improvements of the AMR technique are likely to replace diagnostic angiography. PMID- 1458810 TI - [Human environment]. PMID- 1458811 TI - Exercise and health. PMID- 1458812 TI - Nutritional needs of children with inflammatory bowel disease. PMID- 1458813 TI - Dietary risk factors for hypertension. PMID- 1458814 TI - Green tea in chemoprevention of cancer. PMID- 1458815 TI - Utilizing exercise in the treatment of obesity. PMID- 1458816 TI - The role of dietary cholesterol in infants. PMID- 1458817 TI - Children's diet and health requirements: preschool age through adolescence. PMID- 1458818 TI - Neglected organization and management issues in mental health systems development. AB - Fragmented and often uncoordinated public services for the more severely mentally ill are often characteristic of the current U.S. mental health system. The creation of local mental health authorities has been promoted as part of a solution, as has happened in Wisconsin at the county level and is championed in the ongoing Robert Wood Johnson Foundation funded innovative service sites for severely mentally ill adults. There are indications that these innovative mental health authorities will fall short of fulfilling their promise. Basic principles from the management and organizations literature are used to identify several organization and management issues that may have been neglected. These include resource management, attention to system goals, monitoring and feedback, and the promotion of desirable interorganizational cultures. PMID- 1458819 TI - Predicting psychiatric symptoms among homeless people. AB - Multiple regression was used to predict psychiatric symptoms among homeless people. The following variables were significant predictors of psychiatric symptoms: current life satisfaction, previous psychiatric hospitalization, the number of stressful life events, social support, problem drinking, and childhood unhappiness. The results are discussed in terms of their policy and practice implications, particularly the need for crisis intervention services and for dual diagnosed clients. PMID- 1458820 TI - Social support and quality of life of community support clients. AB - Two aspects of social support, availability and adequacy, were assessed for 729 severely mentally ill adults enrolled in seven state-supported Community Support Services (CSS) programs as part of repeated questionnaire surveys nine months apart. Perceived quality of life interviews with the clients were also conducted at both times. These interviews included the Bradburn Positive and Negative Affect Scales and the Satisfaction with Life Domains Scale (SLDS). Availability of social support was significantly correlated with positive affect over time, but not with negative affect at either point. Inadequacy of social support was significantly related to negative affect at both assessments. Both availability and adequacy of social support were significantly related to the SLDS at each time. Change in satisfaction with life domains was found to be related to both availability and, to a lesser degree, with adequacy of social support. PMID- 1458821 TI - Informal systems of care for the chronically mentally ill. AB - The purpose of this paper is to describe the structure and functioning of informal caregiving systems of community-based chronically mentally ill individuals. From a sample of 409 family member reports, 150 caregiving systems are described in terms of size, composition and division of caregiving labor. Results show that these systems are about as large as those found for elder caregiving systems, that women and relatives predominate as caregivers, that there is considerable diversity in the types of caregivers and that size and composition are related to the division of labor observed in these systems. PMID- 1458822 TI - Clinical issues in social network therapy for clients with schizophrenia. AB - Social networks are viable foci for therapeutic interventions. A social network therapy program for clients with schizophrenia was developed by a community-based mental health agency. This paper presents four of the most common clinical issues encountered and illustrates each with a case example. PMID- 1458823 TI - A comparison of how families and their service providers rate family generated quality of service factors. AB - This paper presents a method which was utilized to obtain family consensus around the criteria which should be used to evaluate family support programs. Twelve family members of persons with developmental disabilities were selected in each of six different sites to participate in a group process to identify the factors which distinguish quality family support programs. Content analysis of the results of the six meetings resulted in a final list of 15 quality factors. Two hundred and sixty one families and their family support coordinators (N = 65) were asked to rate the importance of each factor on a 10 point scale. Analysis revealed that there was high agreement between families and their coordinators on the importance of all 15 factors. The applicability of the method used to obtain family consensus regarding evaluation criteria for community mental health agencies is discussed. PMID- 1458824 TI - The quality assurance dilemma in psychiatry: a sociological perspective. AB - Tensions between mental health practitioners and their colleagues in quality assurance can be reduced. A sociological view of the evolution of psychiatric practice from the doctor-patient dyad to the therapist-patient-third party triad and of the discontinuity between the new structure and the culture of professional practice frames the discussion. Drawing on approaches to quality developed in business settings, it is argued that third parties as well as patients are "customers" and that a different approach to quality is appropriate to each. Crosby's methodology is recommended as relevant to the management of relationships with third parties. PMID- 1458825 TI - A family of retinal S-antigens (arrestins) and their genes: comparative analysis of human, mouse, rat, bovine and Drosophila. PMID- 1458826 TI - Triacylglycerol biosynthesis in bovine liver and subcutaneous adipose tissue. AB - 1. Adipose tissue from Angus and Brahman steers incubated with [1-14C]palmitate in the absence and presence of glucose exhibited a greater rate of lipid production than liver (P < 0.05). 2. Homogenates of adipose tissue used in the glycerol-3-phosphate acyltransferase assay exhibited a greater glycerolipid specific activity (nmol lipid/mg protein/30 min) when compared to liver (P < 0.05). 3. The inverse was true for liver homogenates when calculated for tissue activity (nmol lipid/g tissue/30 min). 4. Lysophosphatidate was produced in greater (P < 0.05) amounts than all other glycerolipids in the glycerol-3 phosphate acyltransferase assay. 5. The activity of phosphatidate phosphohydrolase in liver homogenates displayed greater rates than their respective adipose tissue homogenates. 6. Diacylglycerol acyltransferase activity was greater in adipose tissue homogenates compared to liver homogenates. PMID- 1458827 TI - Purification and biochemical properties of calmodulin in Entamoeba histolytica and its distribution during secretion of electron-dense granules. AB - 1. Calmodulin (CaM) was detected during secretion of electron-dense granules by Entamoeba histolytica trophozoites with immunofluorescence. 2. It was purified to apparent homogeneity by chromatography with a yield of 2.26 micrograms of calmodulin/mg of protozoan protein. Purity was established by gel electrophoresis. 3. The parasite calmodulin has properties characteristic of calmodulin isolated from other eukaryotes: an apparent molecular weight of 19 or 17 kDa in presence of EGTA or CaCl2, respectively, activation in a calcium dependent manner of bovine heart cyclic nucleotide phosphodiesterase, and its UV spectrum. PMID- 1458828 TI - The critical role of asparagine 502 in post-translational alteration of protein 4.1. AB - 1. Protein 4.1 in most mammalian red cells exhibits a post-translational conversion of 4.1b to 4.1a, except for feline protein 4.1, which lacks this alteration. 2. Our previous study provided evidence that protein 4.1b in human red cells is converted to 4.1a by deamidation of a specific asparagine (Asn) residue at position 502, suggesting that the post-translational change of 4.1b to 4.1a depends on the primary structure of the protein at the site of deamidation. 3. To confirm this hypothesis, proteolytic fragments corresponding to the deamidation site of human protein 4.1 were purified from canine and feline erythrocyte protein 4.1 and analyzed for their amino acid sequences. 4. Two proteolytic peptides, D7 and D9 derived from canine protein 4.1, both corresponding to the human sequence Thr492-...-Asn (or Asp)502-...-Lys505 showed the same sequence, Thr-Gln-Thr-...-Lys, except that the 11th residue equivalent to the 502nd amino acid was Asn in D7 while it was Asp in D9, indicating that deamidation occurs at the same position in canine protein 4.1 as in humans. 5. However, substitution of Ser for Asn at this position was observed in feline protein 4.1. 6. These results demonstrate that Asn502 has a critical role in post translational conversion of 4.1b to 4.1a in mammalian red blood cells. PMID- 1458829 TI - Chicken leg muscle alpha-connectin as studied by a monoclonal antibody to the 1200 kDa fragment. AB - Chicken leg gracilis muscle contained only alpha-connectin (ca 3000 kDa) without beta-connectin. When myofibrils were kept standing for 20 hr at 4 degrees C, alpha-connectin was degraded to beta-connectin (ca 2000 kDa) and 1200 kDa peptide. The latter was prepared from myofibrils and purified by gel filtration in the presence of SDS. A monoclonal antibody, alpha 7, to this 1200 kDa fragment was prepared. The antibody reacted with the 1200 kDa fragment and its mother molecule alpha-connectin, but not with beta-connectin. Immunoelectron microscopy using alpha 7, as well as other antibodies to chicken breast muscle beta connectin, revealed that the 1200 kDa peptide covered the portion of alpha connectin from the Z line to the N2 line region in the I band of chicken leg gracilis muscle sarcomeres. The results were in good agreement with those observed in rabbit skeletal muscle. PMID- 1458830 TI - Comparative characterization of liver glycogen metabolism in rat and guinea-pig. AB - 1. Guinea-pig liver contained more phosphorylase in the active (phosphorylated) form and less synthase in the active (dephosphorylated) form when compared with rat liver. 2. Activities of cyclic AMP-dependent protein kinase and Ca(2+) dependent phosphorylase kinase were the same in rat and guinea-pig livers. 3. Activities of phosphorylase phosphatase and synthase phosphatase in the extract and glycogen plus microsomal fraction of guinea-pig liver were significantly lower than those of rat liver. 4. The existence of inhibitor-1 in the liver of guinea-pig can maintain a lower activity of type-1 protein phosphatase, especially when inhibitor-1 is phosphorylated by cyclic AMP-dependent protein kinase. PMID- 1458831 TI - A comparative study of Drosophila phenylalanine hydroxylase with a natural and a synthetic tetrahydropterin as cofactor. AB - 1. Phenylalanine hydroxylase activity has been analyzed in Drosophila melanogaster using as cofactors the natural tetrahydropteridine 5,6,7,8 tetrahydrobiopterin (H4Bip) and the synthetic one 5,6-dimethyl-5,6,7,8 tetrahydropterin (H4Dmp). 2. The apparent Vmax and KM for substrate and cofactor showed that the enzyme has two times more affinity for the substrate when H4Bip is the cofactor in the reaction. Similarly to what was found with purified rat liver phenylalanine hydroxylase, H4Bip was the most effective cofactor, leading to 4-5 times more activity than that obtained with H4Dmp. 3. With the natural cofactor H4Bip, no activation of the enzyme with Phe was necessary (in contrast to mammalian phenylalanine hydroxylase), and this tetrahydropteridine inhibits phenylalanine hydroxylase activity when the enzyme is exposed to it before phenylalanine addition. With the synthetic H4Dmp, both types of preincubations led to an increase of phenylalanine hydroxylase activity. 4. The enzyme is highly unstable compared to mammalian phenylalanine hydroxylase, even at -20 degrees C. 5. Thorax and abdomen extracts caused significant inhibition of phenylalanine hydroxylase activity from third instar larvae or newborn adult head extracts, when assayed with the synthetic cofactor H4Dmp. This inhibition did not happen with H4Bip. The presence of the pteridine 7-xanthopterin in adult bodies was not the cause of this inhibition. PMID- 1458832 TI - Purification of a novel heterodimer from shark (Carcharhinus plumbeus) serum by gel-immobilized metal chromatography. AB - 1. Resolution of the fraction of sandbar shark (Carcharhinus plumbeus) serum that was soluble in 50% saturated ammonium sulfate by gel-immobilized metal-affinity chromatography allowed the isolation of a novel disulfide-bonded heterodimer of intact mass 70 kDa. 2. Following reduction, the molecule could be resolved into two chains of apparent mass 36 and 24 kDa. 3. The molecules were glycoproteins as determined by an observed reduction in molecular weight following enzymatic glycosylation. 4. The two separate chains were related to one another on the basis of amino-acid composition analysis and by comparison of the N-terminal amino acids (seven out of 10 identities). 5. The exact relationship of this molecule to characterized heterodimers of higher vertebrates is unknown. 6. Cross linked agarose-acetate was synthesized and proved to be an efficient concentrating agent and also a hydrophobic interaction adsorbant. PMID- 1458833 TI - Alterations to the permeability of plant and animal mitochondria submitted to Ca2+ releasing agents. AB - 1. Mitochondria from different rat tissues and from plants were compared as regards their sensitivity towards Ca2+ in the presence of different Ca2+ releasing agents, and the phospholipase A2 activity was evaluated in the different mitochondrial preparations. 2. The mitochondria were exposed to Ca2+ and an oxidant such as t-butylhydroperoxide or diamide or to Ca2+ and inorganic phosphate, and plant mitochondria were seen to be much more resistant than liver, brain or kidney mitochondria of rats to the deleterious effects of these agents. 3. The phospholipase A2 activity is not directly involved in the alterations of the mitochondrial inner membrane permeability within the first 10 min of incubation under our experimental conditions. 4. The protection conferred by ATP and Mg2+ against Ca2+ efflux from mitochondria or the decrease in the mitochondrial transmembrane electrical potential was also observed under our experimental conditions, but cannot be attributed to an enhancement of the reacylation of lysophospholipids resulting from the phospholipase A2 activity. PMID- 1458834 TI - The biological properties of venoms from juvenile and adult taipan (Oxyuranus scutellatus) snakes. AB - 1. The biological properties of four venom pooled samples from adult taipan (Oxyuranus scutellatus) snakes and one pooled venom sample from six juvenile taipan snakes (11 months old) were compared. 2. The intravenous LD50 (median lethal dose), procoagulant activity and enzymatic activities of the juvenile venom were not significantly different from those of the adult venoms. 3. The juvenile and adult venoms exhibited similar polyacrylamide gel electrophoretic (PAGE) and SDS-PAGE patterns, indicating that they possessed a similar protein composition. 4. The results suggest that there is no significant age-dependency in the biological properties of taipan venom. PMID- 1458835 TI - Inter- and intra-specific differences in serum proteins of different species and subspecies of zebras. AB - 1. Serum proteins of Equus grevyi, E. zebra hartmannae, E. burchelli boehmi, E. b. chapmanni and E. b. antiquorum were studied using starch-gel electrophoresis, 1-D polyacrylamide-gel electrophoresis, inhibitions of trypsin and chymotrypsin, immunoblotting, and specific staining for esterase. 2. Clear species-specific patterns were observed in albumin, transferrin, and for E. grevyi in protease inhibitor-1. Specific esterase was detected only in E. z. hartmannae. 3. Protein polymorphism was found in all studied species: E. grevyi--transferrin; E. z. hartmannae--protease inhibitor-1; E. b. boehmi--albumin, GC, transferrin, protease inhibitor-1, protease inhibitor-T; E. b. chapmanni--albumin, GC, transferrin, protease inhibitor-1; E. b. antiquorum--GC, transferrin, protease inhibitor-1. 4. Phenotype patterns of the polymorphic proteins were indicative of simple codominant inheritance. Further studies of polymorphism of protease inhibitor-2 and variability of protease inhibitor-X are needed. 5. alpha 1B glycoprotein in all zebra species was monomorphic. 6. The main transferrin components and alpha 1B glycoprotein of zebra (E. b. boehmi) were characterized for terminal sialic acid content. PMID- 1458836 TI - Tissue distribution of insulin-like growth factor receptors in the turkey. AB - 1. The distribution and relative insulin-like growth factor (IGF) binding capacities of membranes derived from 14 tissues of the turkey were examined. 2. Affinity cross-linking analyses using [125I]IGF-I and [125I]IGF-II with membranes derived from the liver, pectoralis major muscle, gizzard, heart and brain indicated that both IGFs interact with only type-I IGF receptors on these tissues. 3. There was no evidence for the existence of a type-II IGF receptor in any tissue. 4. Although considerable variation was detected in the molecular weights of the IGF receptor alpha subunits between tissues (112.2-132.9 kDa), these differences did not appear to influence receptor-ligand affinities. PMID- 1458837 TI - Intestinal disaccharidases in the house musk shrew, Suncus murinus: occurrence of sucrase deficiency. AB - 1. Disaccharidase activities of the small-intestinal brush border membrane were studied in six laboratory lines of the house musk shrew, Suncus murinus. 2. Sucrase activity was detected in all shrews of one line, but not in any shrew of three lines. In the other two lines it was found in some shrews, but not in the others. 3. Maltase, isomaltase, trehalase and lactase activities were found in all shrews of all the lines examined. 4. Sucrase was normally associated with isomaltase to form an enzyme complex. 5. Detergent-solubilized isomaltase, whether associated with sucrase or not, was inhibited by antibodies against rabbit sucrase-isomaltase to almost the same extent as the rabbit one, suggesting that isomaltase is not affected by a mutation(s) in sucrase. PMID- 1458838 TI - North-south regional variation in phospholipase A activity in the venom of Crotalus ruber. AB - 1. Twenty-seven individual venoms from the rattlesnake species Crotalus ruber from different regions were comparatively analyzed by reverse-phase HPLC and analyzed for phospholipase A (PLA) content using a polarographic assay. 2. Two fractions containing PLA activity were detected by HPLC in the venoms of all the C. ruber specimens from southern Baja, Mexico, but specimens from southern California, U.S.A., were lacking corresponding fractions and were extremely low or lacking in PLA activity in their venoms. 3. The north-south regional variation in PLA content in C. ruber venom does not correlate with the north-south ranges (based on external morphology) of the subspecies C. ruber ruber and C. ruber lucasensis. PMID- 1458839 TI - Nucleotide sequence and presumed secondary structure of the internal transcribed spacers of rDNA of the pea aphid, Acyrthosiphon pisum. AB - 1. Internal transcribed spacer (ITS) 1 and ITS 2 of rDNA of the pea aphid, Acyrthosiphon pisum consisted of 229 and 280 nucleotides, whose G+C contents were 70 and 74%, respectively. 2. Secondary structure models constructed for the ITS 1 and ITS 2 suggested that certain structural motifs have been conserved in these regions despite extensive divergence in nucleotide sequence due to species. PMID- 1458840 TI - Epidermal growth factor (EGF) stimulation of ATP citrate lyase activity in isolated rat hepatocytes is age dependent. AB - 1. The effect of epidermal growth factor (EGF) on ATP citrate lyase activity was determined in freshly isolated hepatocytes from rats of different ages as a function of incubation time, EGF concentration and hepatocyte density. 2. The activity of this enzyme was responsive to both dose and time of incubation of EGF with a two-fold increase in ATP citrate lyase activity and a half-maximal effect between 10(-12) and 10(-11) M. 3. EGF effects were detectable by 5 min. 4. The age of the rats had a strong effect on the magnitude of the EGF effect with ATP citrate lyase activity in younger (8 weeks) rats being more responsive than in older (14 weeks) rats. PMID- 1458841 TI - Purification, biochemical characterization and N-terminal sequence of a serine protease with chymotrypsic and collagenolytic activities in a tropical shrimp, Penaeus vannamei (Crustacea, Decapoda). AB - 1. Two chymotrypsin variants, with collagenolytic activities, were purified from the hepatopancreas of Penaeus vannamei using radioactive protein as the substrate. 2. These proteases are very close as far as amino acid composition, molecular weight, inhibitors studies and specificity against small synthetic substrates are concerned. 3. N-terminal amino acid sequences of both variants are identical and are very close to other known crustacean serine proteases. PMID- 1458842 TI - Characterization of the eggshell of Haemonchus contortus--I. Structural components. AB - 1. By transmission electron microscopy, the eggshell of Haemonchus contortus was seen to be similar to previously studied nematodes, with an outer vitelline layer bounded by a trilaminate membrane, a broad medial region, containing chitin, and an electron dense basal region, containing lipid and protein. 2. Exposure of Haemonchus contortus eggs to proteases resulted in disruption of the shell with removal of components of the outer, medial and basal regions. Exposure to chitinase depleted fibrillar components of the medial region of the shell, while collagenase had no effect. 3. Chloroform/methanol extraction of fresh eggshells caused a minor condensation of the outer, vitelline layer and some depletion of the basal layer. 4. After normal hatching, shells appeared similar to those treated with protease and chitinase, but also lacked the basal, lipid layer. 5. Extracts of isolated unhatched eggshells and hatched eggshells, and extracts of biotin-labelled whole fresh eggs showed three major protein bands when run on sodium dodecyl sulphate-polyacrylamide gels indicating that these three proteins are most likely structural in nature and do not participate in the release of the larva from the eggshell. 6. Biotin-labelled protein bands were degraded by proteases and chitinase, but not collagenase or lipase. PMID- 1458843 TI - Identification of vitellogenin in the little skate (Raja erinacea). AB - 1. Vitellogenin was isolated from mature female skates by selective precipitation with MgCl2/EDTA followed by chromatography on DEAE-cellulose columns. 2. A single monomer of approximately 205 kDa was identified on 6.0% SDS-PAGE gels. 3. In addition, isolation of yolk proteins with ammonium sulfate yielded proteins of 94 and 38 kDa (putative phosvitins) and putative lipovitellins of ca 105, 91 and 67 kDa. 4. In vivo phosphate incorporation in female and male skates implanted with estradiol indicated that vitellogenin was phosphorylated. 5. Total protein phosphate incorporation was significantly higher in females than male skates. 6. In male skates treated with estradiol, phosphate incorporation increased from 2 days after implantation to a maximum at approximately 11 days after implantation. 7. Determination of the rate of disappearance of 32P-labeled protein suggests a half-life of ca 200 hr in normal female skate plasma. PMID- 1458844 TI - Putative apolipoprotein B-100 in the freshwater turtle Chrysemys picta: effects of estrogen and progesterone. AB - 1. The isolation and purification of a putative apolipoprotein B-100 in the plasma of the freshwater turtle Chrysemys picta is described. 2. The protein was purified through differential ultracentrifugation and subsequent Sepharose 6B column chromatography. 3. The molecular weight of the protein determined by electrophoresis was approximately 350 kDa. 4. An antibody to chicken apolipoprotein B-100 specifically recognizes this 350 kDa protein in Western blots, suggesting its identity with apolipoprotein B-100. 5. An antibody to the putative Chrysemys apolipoprotein B-100-like protein was developed and used in an ELISA to quantitate protein levels in plasma. 6. Acute estrogen treatment increased levels of apolipoprotein B-100 (7.64 +/- 0.79 mg/ml plasma) over that of control animals (5.07 +/- 1.74 mg/ml plasma). 7. In contrast, chronic estrogen treatment reduced apolipoprotein B-100 significantly to 2.94 +/- 0.53 mg/ml plasma (P < 0.05). PMID- 1458845 TI - A comparative study on ceramide composition of cetacean brain gangliosides. AB - 1. Ceramide composition and N-glycolylneuraminic acid content of gangliosides from gray and white matters and myelin of cerebrum and cerebellum were analyzed in eight species belonging to the suborder Odontoceti and two species to Mystacoceti. 2. The most characteristic feature was high contents of C20:0 (10 40%) and C24 species (5-40%). 3. Content of hydroxy fatty acid of C24 species was higher in cerebellum (5-20%) than cerebrum (0-3%). 4. Major component of long chain base was dC18:1 (70-90%). 5. N-glycolylneuraminic acid was found in sperm whale, Dall's porpoise and killer whale (0.1-1.7%). PMID- 1458846 TI - Species-related variations in tissue antioxidant status--I. Differences in antioxidant enzyme profiles. AB - 1. Antioxidant enzyme activity profiles in red cells of man, rabbit, quail, pig and rat have been investigated and found to exhibit striking differences. 2. No direct correlations between activities of "functionally coupled" enzymes (superoxide dismutase/catalase and glutathione peroxidase/glutathione reductase) were apparent, suggesting their independent regulation. 3. However, activities of red cell catalase and glutathione peroxidase in the various species studied were inversely correlated. 4. This was most evident in quail red cells, which showed negligible catalase activity but the highest levels of glutathione peroxidase of all the species examined. 5. A significant positive correlation between catalase and glutathione reductase activities was also demonstrated. 6. This may be relevant to the suggestion that the binding of NADPH to catalase may serve to decrease the intracellular inactivation of this reducing cofactor which may be limiting in the glutathione reductase reaction. 7. Basal levels of glutathione, which have been claimed to be limiting for the glutathione peroxidase reaction, were found to correlate positively with the activity of this enzyme in red cells. 8. Myocardial tissues also exhibited species-related differences in antioxidant enzyme profiles but these did not bear any obvious relationship to patterns observed in the corresponding red cells. PMID- 1458847 TI - Species-related variations in tissue antioxidant status--II. Differences in susceptibility to oxidative challenge. AB - 1. In order to investigate possible species-related variations in antioxidant capacity, the susceptibility of red cells from various species (e.g. rat, rabbit, pig and quail) to depletion of glutathione (GSH) and formation of malondialdehyde (MDA), an indirect measure of lipid peroxidation, following in vitro oxidative challenge with t-butylhydroperoxide (tBHP) has been examined. 2. Marked differences in sensitivity were found, although the relative order of susceptibilities varied depending on the index of oxidation used. 3. For example, pig erythrocytes showed the highest sensitivity to depletion of GSH but the greatest resistance to tBHP-induced MDA formation. 4. Red cell susceptibility to oxidative stress under the experimental conditions used was not predictable from basal levels of GSH or from the activities of antioxidant enzymes, suggesting a prominent role of non-enzymatic antioxidants. 5. Species-dependent differences in antioxidant capacity were also found to extend to myocardial tissue homogenates and some degree of parallelism was noted with tBHP-induced MDA formation in red cells of the same species. 6. Thus, the relative resistance of both tissues from pig contrasted with the high susceptibility of red cells and myocardium from rat and quail. 7. This parallelism allows the suggestion that the functional consequences of antioxidant interventions might be discernible from measurements involving red cells. 8. Our findings may have potentially important implications in the interpretation and comparison of data obtained with experimental models of disease states in which oxidative processes are implicated when differences in species are involved. PMID- 1458848 TI - Purification and characterization of a humoral opsonin from the solitary urochordate Styela clava. AB - 1. We have previously identified opsonic activity in the plasma of the solitary urochordate, Styela clava. 2. Here, we report the purification and further characterization of the opsonic molecule. 3. Two purification methods were employed. 4. Gel filtration yielded one strongly opsonic fraction that contained a single, electrophoretically-resolved protein. 5. Opsonic activity was dose dependent and sensitive to tryptic digestion and heat denaturation. 6. SDS-PAGE and calibrated gel filtration indicated the opsonic protein was a 17.5 kDa monomer while isoelectrofocusing indicated a single pI of 7.0. 7. In an alternative procedure, a similar opsonic activity and protein were isolated by affinity purification using whole yeast cells. PMID- 1458849 TI - Analysis of the causes of the suppression of oxidative phosphorylation and energy dependent cationic transport into liver mitochondria of hibernating gophers, Citellus undulatus. AB - 1. The causes of the suppression of oxidative phosphorylation and energy dependent cationic transport into liver mitochondria of hibernating gophers have been analysed. 2. The decrease of the ATP synthesis rate and suppression of the energy-dependent K(+)- and Ca(2+)-transport into mitochondria during hibernation has been found to be mainly related to a delta psi decrease in mitochondria of hibernating gophers. 3. The increase delta psi upon incubation of the mitochondria of hibernating animals in a hypotonic medium results in an essential acceleration of ATP synthesis and energy-dependent cationic transport. PMID- 1458851 TI - Numerical phase algorithm for decompression computers and application. AB - Present generation decompression computers employ a simplified algorithm, limiting dissolved gas build-up in tissue and blood according to a method proposed by Haldane 80 years ago. Such a model works well for single dives, but is usually liberal and theoretically incomplete for multiple exposures within 24 hr spans. Using the critical phase hypothesis in a bubble model, we have extended the classical model of Haldane to multi-exposures. This model is discussed, and a decomputer algorithm described for multi-diving. The focus is permissible bubble excess, not just dissolved gas per se, with phase constraints affecting all tissues, fast and slow, and requiring a systematic lowering of repetitive tissue tensions. Deep repetitive and shallow multi-day exposures are impacted most by the procedure. Within nucleation theory deeper-than-first dives are also treated. A set of multi-diving fractions, xi, accounting for micronuclei excitation and regeneration, reduced bubble elimination in repetitive activity, and coupled effects on tissue tension, are proposed, with xi representing a set of multiplicative factors (less than one) applied to critical tissue tensions for multi-exposures. These factors affect repetitive activity over short time spans, deeper-than-previous and continuous multi-day activities, compared to standard computer software, and are easily encoded into existing decompression meters, potentially extending their range and flexibility over exposure regimes. PMID- 1458850 TI - On AR modelling for MEG spectral estimation, data compression and classification. AB - The use of the autoregressive (AR) model for magnetoencephalogram (MEG) processing is examined and compared to other methods. Spectral estimation, classification and data compression of MEG signals are studied. In application to spectral estimation the AR model is compared to the classical modified periodogram method. Also, AR modelling appears to perform very successfully when used for the classification of normal and epileptic MEG signals. Finally, the 17:1 to 23:1 data compression achieved by AR modelling, along with the above mentioned advantages, render it suitable for storage applications. For comparison, the method of feature selection via orthogonal expansion is used as a tool to achieve data reduction. It is seen that while effective, this is less drastic than the compression of data volume achieved by AR modelling. PMID- 1458852 TI - Automatic computer analysis of transients in EEG. AB - The electroencephalogram (EEG) is often used for the diagnosis of diseases and functional disturbances in the brain. In this paper, new algorithms developed for the automatic detection of transients in EEG are described. The single spike, and spike and wave bursts, both of which are abnormal phenomena associated with epileptic activity are considered. The algorithms for detecting these transients were tested using real EEG data. The transient detection is enhanced by two classification algorithms: patient-independent analysis and patient-dependent analysis. In the patient-independent analysis, multiple reference templates are generated from a patient population and for the patient-dependent analysis, the spikes from the patient's own EEG recording is used as reference. The description of the algorithms and their performances are presented. PMID- 1458853 TI - Development and testing of a PC-based system with menu-driven software for evaluating lung function in ICU patients. AB - This paper describes a portable PC-based system for measuring respiratory system resistance (Rrs) and dynamic lung compliance (Cdyn) in intubated and mechanically ventilated patients. A pneumotachometer placed immediately proximal to the endotracheal tube measures flow, and a pressure catheter with its tip at the distal end of the endotracheal tube measures lateral airway pressure. The software is menu driven and allows the user to select from options including patient information display and entry, data collection, data editing, and waveform display. Up to ten consecutive breaths can be analyzed per run. Rrs and Cdyn are calculated on a breath by breath basis. Results are displayed to the screen, output to the system printer, and written to a user-specified ACSII data file. The system was tested by measuring resistance and compliance in a model of the lung, and results compared with those calculated from analog signals. It was then used to make measurements in intubated post-operative patients. Results were comparable to those previously reported in intubated ICU patients without primary lung disease. We conclude that our system provides reliable measurements of lung mechanics in the intubated patient, and represents an inexpensive and more versatile alternative to microprocessor-based ventilator systems currently being marketed. PMID- 1458854 TI - A fitness analysis system with an intelligent interface. AB - This paper describes the development of a system with an intelligent interface for analysis of physiological correlates of athletes' physical performance capacities. The system improves the interface between the physiologist and the coach and provides scientific information in a systematic and coherent fashion. The recommendations provided are based on the results of a series of physiological tests. The implementation of the system is described with emphasis placed on recognition of the internal structure of the knowledge, independence from a particular shell, design for future expansion and maintenance and the integration with existing information resources. PMID- 1458855 TI - Validation of the medical expert system PNEUMON-IA. AB - The present study validates the expert system PNEUMON-IA. The aim of PNEUMON-IA is assessing the etiology of community-acquired pneumonias from clinical, radiological, and laboratory data obtained at the onset of the disease. Validation was performed using data from medical records of 76 patients with proven clinical diagnosis of pneumonia. The etiological diagnoses provided by PNEUMON-IA were compared to those established by five specialists unrelated to the development of the expert system. For each etiological possibility, both PNEUMON-IA and the experts provided a causal possibility, expressed as a linguistic label (i.e., "almost impossible"). Linguistic labels were then converted to numeric values. In the majority of cases, an etiological diagnosis was unavailable to be used as a gold standard. To overcome this limitation, distances between arrays of etiological possibilities given by specialists and by PNEUMON-IA were considered as an agreement measure between diagnoses. Cluster analysis based on those distances was used to classify PNEUMON-IA among experts. Results showed the same differences between specialists and PNEUMON-IA as among the specialists themselves. The method used to validate PNEUMON-IA could prove useful to assess the performance of expert systems in fields where no gold standard is available. PMID- 1458856 TI - Plots for examination of univariate twin data. AB - We discuss informative plots for univariate twin data that can be used in conjunction with twin data analyses. The plots are useful for spotting outliers, spotting possible single gene effects, and displaying the contribution of individual twin pairs to the fit of genetic models of the data. We illustrate the use of the plots on bone mineral data, and present programs for generating the plots in SAS. PMID- 1458857 TI - Reconstruction of the electrocardiogram during heart surgery. AB - Electrocardiograms (ECG) recorded during arrhythmia surgery are used for identification of arrhythmias of different morphology. However, the interpretation of an intraoperative ECG is difficult because some leads cannot be recorded and the signals of the remaining leads often differ from those of a preoperative recording because of the sternotomy. Therefore, a method for reconstruction of a complete intraoperative ECG, which resembles a preoperatively recorded ECG, was studied in 24 patients undergoing heart surgery. The reconstruction method involves calculating coefficients for a transformation matrix, using a preoperative ECG recording and a first intraoperative ECG recording. Once this matrix has been established, further intraoperative recordings can be transformed into an ECG which strongly resembles a preoperative ECG. The correlation between reconstructed intraoperative leads and the corresponding preoperative leads was high in the leads Vx and Vy (median correlation coefficient 0.98 and 0.97) and slightly smaller in lead Vz (0.94). Further studies will prove if the method can be useful in arrhythmia surgery. PMID- 1458858 TI - A parallel implementation of the backward error propagation neural network training algorithm: experiments in event identification. AB - An artificial neural-network-based (ANN) event detection and alarm generation system has been developed to aid clinicians in the identification of critical events commonly occurring in the anesthesia breathing circuit. To detect breathing circuit problems, the system monitored CO2 gas concentration, gas flow, and airway pressure. Various parameters were extracted from each of these input waveforms and fed into an artificial neural network. To develop truly robust ANNs, investigators are required to train their networks on large training data sets, requiring enormous computing power. We implemented a parallel version of the backward error propagation neural network training algorithm in the widely portable parallel programming language C-Linda. A maximum speedup of 4.06 was obtained with six processors. This speedup represents a reduction in total run time from 6.4 to 1.5 h. By reducing the total run time of the computation through parallelism, we were able to optimize many of the neural network's initial parameters. We conclude that use of the master-worker model of parallel computation is an excellent method for speeding up the backward error propagation neural network training algorithm. PMID- 1458859 TI - Evaluation of a computer program for teaching laboratory diagnosis of acid-base disorders. AB - A computer program was evaluated as a tool for increasing the diagnostic acumen of medical housestaff and students in identifying acid-base disorders. The participants were randomized into two groups; group A (N = 20) was encouraged to use the software, and group B (N = 19) was denied access. Pre- and post-tests were administered to delineate the groups' ability to identify correctly an acid base disorder from laboratory data (electrolytes and arterial blood gas). During 6 weeks, group A used the computer for a mean of 2.83 h (range 1 to 6). The mean +/- SE number of correct answers out of 20 questions, prior to use of the computer program, were 5.7 +/- 0.8 (95% confidence interval 3.9 to 7.5) for group A and 5.2 +/- 0.6 (95% confidence interval 3.9 to 6.5) for group B. These results were not statistically different. Correct responses increased significantly in group A to 10.3 +/- 0.9 (P < 0.0001, 95% confidence interval 8.4 to 12.2) but did not increase significantly in group B. The data suggest that this software program was effective in increasing the diagnostic capabilities of medical housestaff and students for identifying acid-base disorders. PMID- 1458860 TI - A neural network architecture for understanding discrete three-dimensional scenes in medical imaging. AB - Magnetic resonance and computed tomography produce sets of tomograms which are termed discrete 3D scenes. Usually, discrete 3D scenes are analyzed in two dimensions by observing each tomogram on a screen so that the three-dimensional information contained in the scene can be recovered only partially and qualitatively. The three-dimensional reconstruction of the shape of biological structures from discrete 3D scenes would allow a complete and quantitative recovery of the available information, but this task has proved hard for conventional processing techniques. In this paper we present a system architecture based on neural networks for the fully automated segmentation and recognition of structures of interest in discrete 3D scenes. The system includes a retina and two main processing modules, an Attention-Focuser System and a Region-Finder System, which have been implemented by using feed-forward nets trained with the back-propagation algorithm. This architecture has been tested on computer-simulated structures and has been applied to the reconstruction of the spinal cord and the brain from sets of tomograms. PMID- 1458861 TI - The chronic disease data bank model: a conceptual framework for the computer based medical record. AB - The principles underlying the chronic disease data bank model are straight forward: (1) the purpose of medical care is to improve patient outcomes; (2) patient outcomes in contemporary developed societies are overwhelmingly linked to chronic illnesses and degenerative processes and will become increasingly so; (3) such outcomes have multiple determinants including the psychological and social, as well as the biologic; (4) outcome antecedents (risk factors) may precede clinical illness by years or decades; and (5) these complex characteristics require for their study (a) computer aid and (b) longitudinal data. The chronic disease data bank provides an important resource, available to many investigators, for examination of the complex set of clinical and policy questions arising with long-term illness and addressing the questions of lifetime health. The chronic disease data bank consecutively enrolls eligible subjects, follows them for life, and amasses time-oriented, multidisciplinary data including clinical findings, medical history, demographics, treatments, resource utilization and disease outcomes, and assessing both the quality of life and its duration. Analyses are longitudinal and time-series in type, examining changes in trends and tempo of the disease, and are focused upon long-term outcomes. Outcomes are regularly and carefully assessed, and include the outcome dimensions of death, disability, discomfort, iatrogenic toxicity, and dollar cost. Specific studies address the description of the disease from biologic, demographic, economic, and social viewpoints, identify the factors associated with good and bad outcomes, and assess the effects of treatment, both good and ill. The clinical and policy goals are focused upon delaying transitions from more benign disease states to more serious ones, thus improving both longevity and the quality of life. The time is appropriate to consider generalization of the chronic disease data bank model to the usual clinical care situation, with large rewards in improvement of the quality of care. The traditional medical record lacks systematic documentation of end results and of important covariates related to health risks. As such, it cannot readily be used to assess the ultimate quality of care and to establish a feedback loop to change behaviors and thereby improve outcomes. It is weak where the chronic disease data bank is strong. The technology is transferable. PMID- 1458862 TI - GOFCOX: a computer program for the goodness-of-fit analysis of the Cox proportional hazards model. AB - GOFCOX is a user-friendly FORTRAN program for assessing the adequacy of the Cox proportional hazards model. The underlying methodology is based on the comparison of the maximum partial likelihood estimator and a weighted parameter estimator. The latter is the root to an estimation equation that assigns varying weights to the individual contributions to the partial likelihood score function. The weighted and unweighted parameter estimators have the same expectation under the Cox model, but tend to differ when the model is inappropriate. The GOFCOX program computes a rich class of weighted parameter estimators and corresponding goodness of-fit test statistics. The program runs on both mainframe computers and microcomputers. The running time is minimal even for large data sets. A simple example is provided to illustrate the features of the program. PMID- 1458863 TI - Computer quantitation of saturation impairment time as an index of oxygenation during sleep. AB - The measurement of oxygenation during sleep has become a standard procedure in the assessment of hypoxemia in patients with various disorders. However, an accepted method for quantitating this hypoxemia is not available. This study describes the development of computerized data acquisition and analysis programs to quantitate nocturnal hypoxemia in patients with sleep and breathing disorders. The acquisition program samples the voltage output from pulse oximeters used to measure oxyhemoglobin saturation (SpO2) and stores this on an IBM PC or compatible computer. The analysis program integrates the SpO2 over time below the patient's pretest baseline as well as the integral below 90, 80, 70, 60 and 50% saturation. We refer to each integral as Saturation Impairment Time or SIT. In order to compare these integrals between patients or between the same patient but different studies, the integral is divided by the total sleep study time. We refer to each of these integrals, corrected for sleep study time, as the SIT index. Evaluation of the SIT index in 10 consecutive patients referred for various sleep disorders revealed acquisition program detection and deletion of 48 of 57 (86%) oximeter probe artifacts (mean duration of 3 seconds for undetected artifacts). There were no significant artifacts in the analysis program calculation of the SIT index in these same patients. In conclusion, computer programs were developed to measure and quantitate oxygen saturation measured by oximeters. Preliminary results reveal an accuracy of measurement which should prove acceptable in further clinical evaluations. PMID- 1458864 TI - EMSA: a SAAM service for the estimation of population parameters based on model fits to identically replicated experiments. AB - This paper presents a new technique for the aggregation of models to produce population parameter estimates based on a set of identically replicated experiments. After describing the theoretical basis for the technique we discuss tactical and strategic issues associated with its implementation in the SAAM software. Finally, we demonstrate its utility in the aggregation of models fitted to four simulated experiments. PMID- 1458865 TI - Cohen's weighted kappa with Turbo Pascal (FORTRAN). AB - A microcomputer based Turbo Pascal and FORTRAN program for Cohen's weighted kappa (kappa w) is given. Three clinical applications for kappa w are also presented. A typical data file, the Pascal and FORTRAN program listing and corresponding output are given. PMID- 1458866 TI - TWINAN90: a FORTRAN program for conducting ANOVA-based and likelihood-based analyses of twin data. AB - We discuss the program, TWINAN90, which can perform several different types of analysis of twin data. TWINAN90 incorporates the ANOVA-based twin analyses from the TWINAN twin analysis program, and also includes maximum likelihood estimation of parameters from three path models. Another feature of TWINAN90 is the optional output of a pedigree file which can be read by the quantitative genetics package FISHER. The diagnostic features of the program make TWINAN90 useful also for preliminary analyses prior to the use of more sophisticated modeling procedures which are available in packages such as LISREL and FISHER. An annotated printout from TWINAN90 is presented to illustrate the statistical analyses performed in the program. PMID- 1458867 TI - An integrated system for quantitation of chemotaxis using a 48-well millipore filter assay. AB - We have established a computerized system for quantification of human neutrophil motility using a 48-well chemotaxis assay. The software is primarily written in the Unix C-shell and is designed to integrate with standard statistical and graphics packages and permit analysis either under Unix or MS-DOS. We demonstrate how simple image analysis techniques may be used to count neutrophils that have traversed a polycarbonate filter. Methods of optical optimization, cell counting and integration with the Statistical Analysis System (SAS) are presented. PMID- 1458868 TI - CD-ROM source data uploaded to the operating and storage devices of an IBM 3090 mainframe through a PC terminal. AB - A powerful method of processing MEDLINE and CINAHL source data uploaded to the IBM 3090 mainframe computer through an IBM/PC is described. Data are first downloaded from the CD-ROM's PC devices to floppy disks. These disks then are uploaded to the mainframe computer through an IBM/PC equipped with WordPerfect text editor and computer network connection (SONNGATE). Before downloading, keywords specifying the information to be accessed are typed at the FIND prompt of the CD-ROM station. The resulting abstracts are downloaded into a file called DOWNLOAD.DOC. The floppy disks containing the information are simply carried to an IBM/PC which has a terminal emulation (TELNET) connection to the university wide computer network (SONNET) at the Ohio State University Academic Computing Services (OSU ACS). The WordPerfect (5.1) processes and saves the text into DOS format. Using the File Transfer Protocol (FTP, 130,000 bytes/s) of SONNET, the entire text containing the information obtained through the MEDLINE and CINAHL search is transferred to the remote mainframe computer for further processing. At this point, abstracts in the specified area are ready for immediate access and multiple retrieval by any PC having network switch or dial-in connection after the USER ID, PASSWORD and ACCOUNT NUMBER are specified by the user. The system provides the user an on-line, very powerful and quick method of searching for words specifying: diseases, agents, experimental methods, animals, authors, and journals in the research area downloaded. The user can also copy the TItles, AUthors and SOurce with optional parts of abstracts into papers under edition. This arrangement serves the special demands of a research laboratory by handling MEDLINE and CINAHL source data resulting after a search is performed with keywords specified for ongoing projects. Since the Ohio State University has a centrally founded mainframe system, the data upload, storage and mainframe operations are free. PMID- 1458869 TI - Cardiology education using hypermedia and digital imagery. AB - A computer-based educational system for the study of cardiovascular imaging is described. This system, based on HyperCard * and a standard Macintosh II, integrates hypertext retrieval, computer graphics, sound, and medical images into a single interactive environment stored on a standard hard disk. This 'hypermedia' approach allows arbitrary complexity coupled with direct, immediate, easy traversal of the images and related text, which provides the opportunity for students to move at their own pace, choose their own direction through the material and repeat as often as desired. Storage on magnetic medium allows for easy updating with new studies and material in order to keep pace with advances in medical imaging technology. The system could be mastered onto CD-ROM for ease of distribution if so desired. The system includes a tutorial on the basics of digital image representation and example studies from cineangiography, nuclear medicine, echocardiography and magnetic resonance imaging of the heart. Quantitative techniques for evaluation of left ventricular function are explained using computer graphics overlays on the original medical images. Color encoded functional images are also included as an aid to visualization of ventricular performance data. The system has proven useful as a primer for digital imaging in cardiology prior to specific case study in a traditional mentor relationship. PMID- 1458870 TI - Influence of thyroid status regulation and Synovex-S implants on growth performance and tissue gain in beef steers. AB - The separate and combined effects of Synovex-S (SYN) ear implants and thyroxine (T4)-5'-monodeiodinase inhibition (Trial 1) and T3 injection to create a mild elevation in circulating T3 concentrations (Trial 2) on BW gain and composition of gain were studied. Trial 1 used 24, 285-kg Angus steers in two experimental phases. Low-level feeding of propylthiouracil (PTU, 1.5 mg/kg BW daily) was used to achieve inhibition of T4-5'-monodeiodinase activity (TMA). Twelve steers received neither treatment (control) and 12 received SYN+PTU (hypothesized to maximize weight gain) from 0 to 56 d (phase 1) in a single factor treatment comparison. Subsequently, PTU was fed to six control steers and not fed to six of the original SYN+PTU steers from 56 to 175 d (phase 2) in a 2 x 2 arrangement of treatments. Trial 2 used 24, 302-kg Angus-Hereford steers. Treatments were without or with SYN and without or with sc injections of T3 in polyethylene glycol (2 micrograms/kg BW every 48 hr) in a 2 x 2 factorial arrangement of treatments. In both trials, all steers were individually fed a diet of a corn based concentrate and silage mixture at an equal metabolizable energy intakes per unit of metabolic body weight (.25 Mcal/kg BW.75). Measurements of daily dry matter intakes, weekly BW, 28-d estimates of empty body components (measured by urea dilution), final TMA (trial 1) and plasma thyroid hormone concentrations were obtained. In both trials, SYN increased BW gain and protein accretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458871 TI - Opioid modulation of the hypothalamo-pituitary-adrenal axis in dairy cows. AB - Plasma cortisol responses to an intravenous bolus treatment with 250 mg naloxone, 300 mg morphine or a combination, were studied in Holstein-Friesian cows; 4 in early lactation (29-43 d postpartum) and 7 in mid-lactation (90-155 d post partum). Blood samples were collected every 15 min from 60 min before to 90 min after treatment. Naloxone induced an immediate increase in cortisol concentration, reaching a peak within 30 min. The cortisol response (area under the curve) was positively correlated with pre-naloxone cortisol concentrations (r = 0.7, p < 0.05). The mean increase in cortisol concentration after naloxone appeared to be lower in early lactation (1.8 ng/ml) than in mid-lactation (8.3 ng/ml). In contrast, morphine consistently suppressed mean tonic plasma cortisol concentration by 2.7 ng/ml below baseline for at least 90 min. When given with morphine, naloxone counteracted the suppressive effects; the cortisol response was similar to that after naloxone alone. A cow in mid-lactation, suffering from chronic lameness (joint infection), gave opposite results, i.e., treatment with morphine alone increased cortisol concentration, whereas morphine with naloxone did not result in the expected large increase in plasma cortisol concentration. In conclusion, the hypothalamo-pituitary-adrenal axis of dairy cows appears to be under suppressive opioidergic control. However, the opioidergic system involved in hypothalamo-pituitary-adrenal functions of an animal under chronic stress behaved in an opposite manner. PMID- 1458872 TI - Is nutritional anestrus precipitated by subfunctional corpora lutea in beef cows? AB - Thirty-four multiparous, lactating, cyclic beef cows which calved in moderate body condition were used to determine effects of restricted nutrition on corpus luteum (CL) development and endocrine status. At 78 d postpartum, six cows were assigned to a control (CON) diet (26.0 Mcal ME), fed to increase bodyweight (BW) and body condition score (BCS), and the remaining 28 cows were fed to lose BW and BCS on a restricted (RES) diet (14.0 Mcal ME). Following a 40-d adjustment period on respective diets, estrous cycles were synchronized and cows bled daily for determination of progesterone (P4), luteinizing hormone (LH) and insulin (INS) beginning at the synchronized estrus. Ultrasonography was used to determine the ovulatory follicle and CL development. Control cows were maintained for one estrous cycle and were ovariectomized on day 11 of their second cycle. Ten cows on restricted diet (RES-C) continued to form a functional CL (P4 > 1.5 ng/ml at day 10 of an estrous cycle) through as many as 5 cycles, after which observations were discontinued. Fourteen cows on restricted diet (RES-A) were ovariectomized on day 11 of a cycle when a CL was identified by ultrasonography, but was subfunctional (P4 < 1.5 ng/ml on day 10 of that cycle). Four additional RES-A cows which had subfunctional CL were not ovariectomized but were bled for an additional 25 d. At ovariectomy, CL and ovarian weights were collected. Luteal tissue was prepared for evaluation of P4 synthesis, LH responsiveness in vitro, and for determination of P4 content and total LH receptors. Bodyweight and BCS increased in CON cows; whereas, RES cows lost BW and BCS (P < .05). In the cycle prior to ovariectomy, serum P4 and LH were not different in 18 RES-A cows which developed subfunctional CL in comparison to CON cows. Four RES-A cows not ovariectomized but bled for an additional 25 d neither exhibited estrus, ovulated, nor had P4 concentrations greater than .3 ng/ml. Serum INS was lower in RES-A cows during the cycle prior to ovariectomy than in CON cows (P < .05). During the 11-d period prior to ovariectomy, mean serum P4 and INS were lower in RES-A cows than in CON cows (P < .05); however, serum LH was not different. Furthermore, CL and ovarian weights, P4 content of CL, secretion of P4 by luteal tissue in response to LH in vitro and LH receptor number were not different between CON and RES-A cows. In conclusion, nutritional anestrus may be preceded by the formation of a CL with lower steroidogenic output in vivo. However, luteal tissue, collected from RES-A cows, did not appear to be subfunctional during in vitro incubation when substrate availability and gonadotropin support were equal between diets. PMID- 1458873 TI - Effect of age and intake on growth hormone kinetics in dairy heifers. AB - The effects of aging and intake on growth hormone (GH) kinetics and GH-releasing factor (GRF)-induced GH concentrations were studied in two groups of 12 Holstein heifers each (80 d, 85 kg: young; and 273 d of age, 246 kg: old). Each group was then equally subdivided into full-fed (FF) and restricted-fed (RF) subgroups. After 11 d of intake treatment, animals were infused for 3 hr with GH (1.5 mg/hr) in order to calculate GH metabolic clearance rate (MCR), secretion rate (SR) and half-life (t 1/2). Two d later, total plasma volume was determined and the following day, all heifers received a GRF challenge (5 micrograms/kg i.v.). The following values are LSM +/- SE for young-FF, young-RF, old-FF and old-RF. Rate of secretion was not affected by any treatment, averaging 1.51, 1.25, 1.34, and 1.40 +/- .23 micrograms/min. Aging increased (P < .01) MCR (186, 159, 382, and 300 +/- 21 ml/min) and increased plasma volume (P < .01), which resulted in lower basal GH concentrations. Aging also decreased (P < .01) the area under the GH response curve following GRF injection (AUC: 12442, 21114, 5155, and 6308 +/- 1776 ng.min/ml) but did not affect average GH quantity in the plasma after the GRF challenge. Feed restriction decreased (P < .05) MCR, but not enough to affect basal GH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458874 TI - Androgens modulate growth hormone-releasing factor-induced GH release from bovine anterior pituitary cells in static culture. AB - Static primary cultures of bovine anterior pituitary (AP) cells were utilized to study the effect of sex steroids on basal growth hormone (GH) and GH-releasing hormone (GRF)-stimulated release of GH. The AP cells (5 x 10(5) cells/well) were allowed to attach for 72 hr and become confluent before treatments were imposed. Cells were incubated for an additional 24, 48 or 72 hr with either estradiol-17 beta (E2, 10(-11) to 10(-8) M), testosterone (T, 10(-8) to 10(-5) M), dihydrotestosterone (DHT, 10(-9) to 10(-6) M) or 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol, 10(-11) to 10(-8) M). Media were collected every 24 hr and GH concentrations determined by RIA. Incubation of calf AP cells with gonadal steroids did not affect (P > 0.05) basal GH released at 24, 48, or 72 hr. In another experiment, calf AP cells were incubated with the same concentrations of the steroids for 24 hr, media harvested, cells washed and challenged in serum free media for 1 hr with bovine GRF 1-44-NH2 (10(-8) M). In non-steroid treated wells, GRF increased (P < 0.05) GH from 58 to 134 ng/ml. Incubation with E2 or 3 alpha-diol did not affect (P > 0.05) GRF-induced GH release; however, preincubation with T (10(-5) M) and DHT (10(-9), 10(-8) and 10(-7) M) increased (P < 0.05) GRF-induced GH release above control concentrations (195, 235, 190 and 185 ng/ml, respectively). At the doses tested, sex steroids did not affect basal release of GH, but androgens increased responsiveness of somatotropes to GRF. PMID- 1458875 TI - Comparative morphometry and steroidogenic function of antral ovine follicles destined for ovulation or atresia. AB - An experimental model was established in the ewe allowing one to predict with accuracy an antral follicle that coincidentally would either undergo ovulation (6 8 mm diameter) or atresia (3-4 mm diameter) following synchronization of luteal regression and the onset of the gonadotropin surge. Quantitative morphometric and hormonal criteria were used to make direct comparisons of such follicles collected throughout the preovulatory period. There were progressive alterations in percentages of granulosa cells exhibiting pyknotic nuclei, dispersion of granulosa cells, oocyte maturation, thecal vascular dynamics and extravasation of leukocytes. Nevertheless, no significant variations in temporal patterns were observed between follicular classification. The most notable anatomical distinction between preovulatory and atretogenic follicles was that the former had come into closer contact with the ovarian surface epithelium. The dominant follicle had a higher capacity than the subordinate follicle to produce estradiol before the gonadotropin surge; however, ensuing profiles of steroidogenic function (i.e., shift from the delta 5 to delta 4 pathway) occurred in parallel. Thus, in many respects the follicular mechanics of ovulation and atresia in the sheep appear analogous. PMID- 1458876 TI - N-methyl-d,l-aspartate stimulates growth hormone and prolactin but inhibits luteinizing hormone secretion in the pig. AB - The effects of n-methyl-d,l-aspartate (NMA), a neuroexcitatory amino acid agonist, on luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) secretion in gilts treated with ovarian steroids was studied. Mature gilts which had displayed one or more estrous cycles of 18 to 22 d were ovariectomized and assigned to one of three treatments administered i.m.: corn oil vehicle (V; n = 6); 10 micrograms estradiol-17 b/kg BW given 33 hr before NMA (E; n = 6); .85 mg progesterone/kg BW given twice daily for 6 d prior to NMA (P4; n = 6). Blood was collected via jugular cannulae every 15 min for 6 hr. Pigs received 10 mg NMA/kg BW i.v. 2 hr after blood collection began and a combined synthetic [Ala15]-h GH releasing factor (1-29)-NH2 (GRF; 1 micrograms/kg BW) and gonadotropin releasing hormone (GnRH; .2 micrograms/kg BW) challenge given i.v. 3 hr after NMA. NMA did not alter LH secretion in E gilts. However, NMA decreased (P < .02) serum LH concentrations in V and P4 gilts. Serum LH concentrations increased (P < .01) after GnRH in all gilts. NMA did not alter PRL secretion in P4 pigs, but increased (P < .01) serum PRL concentrations in V and E animals. Treatment with NMA increased (P < .01) GH secretion in all animals while the GRF challenge increased (P < .01) serum GH concentrations in all animals except in V treated pigs. NMA increased (P < .05) cortisol secretion in all treatment groups. These results indicate that NMA inhibits LH secretion and is a secretagogue of PRL, GH and cortisol secretion with ovarian steroids modulating the LH and PRL response to NMA. PMID- 1458877 TI - Glucose and insulin metabolism in ruminating and veal calves fed high and low fat diets. AB - Holstein male calves were maintained on conventional (milk to 6 wk of age, fed grain and hay after weaning) and veal (milk replacer only) diets to 16 wk of age. Within each of these 2 physiological states (ruminating or non-ruminating), calves were fed low or high fat diets (ruminating: 3 and 10%; veal: 10 and 18%). Glucose tolerance tests were undertaken at 8 and 16 wk of age in each group. Basal concentrations (4 hr postfeeding) and areas under the response curves for plasma glucose and insulin were higher in veal calves (P < .0001). Ruminating calves fed higher fat utilized glucose more readily (smaller areas under the curves for both glucose and insulin, P < .10) than those fed lower fat. Age did not influence basal glucose concentrations (P > .10), but older calves had higher basal insulin (P < .0001) and greater areas under the curves (P < .0005) for both glucose and insulin after a glucose challenge. Rate of clearance (k) was greater in ruminating calves (P < .001). Though rate of clearance in veal calves was slower, larger plasma pool size caused veal calves on average to utilize glucose at a 15% greater rate per kg body weight than ruminating calves. Whereas fat concentration in the diets did not influence glucose metabolism in veal calves, the high lactose content (> 50% of diet dry matter) of veal diets induced severe insulin resistance in these calves. PMID- 1458878 TI - Advances in syncope: a combined approach utilizing head-up tilt testing and electrophysiologic evaluation. AB - The electrophysiological evaluation of syncope of unknown origin yields a diagnosis in approximately 40% of patients. In the presence of structural heart disease ventricular tachycardia is the most common etiology accounting for 20% of cases. Over the past several years head-up tilt table testing with isoproterenol provocation has highlighted the syndrome of neurocardiogenic syncope. This syndrome accounts for an additional 30-40% of patients with syncope. There is compelling evidence that this syndrome involves the Bezold-Jarisch reflex with excessive stimulation of ventricular mechanoreceptors (C-fibers) located predominantly in the inferoposterior portion of the heart. Tilt table testing is now an established tool both for diagnosis of this syndrome and for guiding therapy with beta blockers, disopyramide, theophylline, or alpha-agonists. Tilt table testing combined with invasive electrophysiological testing significantly increases the diagnostic yield in the evaluation of syncope. PMID- 1458879 TI - Arterial substitution in lower extremity trauma: autogenous vein vs polytetrafluoroethylene. AB - This review article compares the two most commonly used grafts, autogenous saphenous vein and polytetrafluoroethylene (PTFE), for treatment of arterial trauma. Late graft occlusion is more common with PTFE, but PTFE may be better in situations where infection is a concern and extra-anatomic bypass is not possible. When infected, saphenous vein is much more of a risk because of its tendency to undergo sudden hemorrhagic disruption. PTFE grafts usually show only moderate suture line bleeding, which alerts the surgeon to the presence of a problem with the graft. PMID- 1458880 TI - Case report: treatment of superior sagittal sinus thrombosis with urokinase. AB - Sagittal sinus thrombosis (SSST) is a rare disease with high mortality. Definitive therapy is not known, but anticoagulation or addressing the underlying etiology have been the most often utilized approaches. We here report the second case of postpartum sagittal sinus thrombosis successfully treated with urokinase. Though there are no studies to support this therapy it may be safe and efficacious in refractory cases. PMID- 1458881 TI - The Connecticut State Medical Society: its antecedents and early history. PMID- 1458882 TI - Once-daily aminoglycosides. PMID- 1458883 TI - Physician negotiations with managed care plans: a primer of antitrust pitfalls. PMID- 1458884 TI - Abortion 1992: looking ahead. PMID- 1458885 TI - Closed vs open medical staffs. PMID- 1458886 TI - House-of-cards debt. PMID- 1458887 TI - LifeStar Helicopter--an overreaction? PMID- 1458888 TI - The multiload IUD--a U.S. researcher's evaluation of a European device. AB - This evaluative review focused on the performance and safety of the Dutch-made Multiload copper IUD, primarily the Multiload-375 (MLCu-375) model which has a longer life expectancy (5 or more years) than the Multiload-250 (MLCu-250) model, usually cited for a life expectancy for three years. This copper-medicated IUD differs from the copper-T IUDs in shape and insertion technique. The review shows that (a) the MLCu-375 IUD seems to be slightly less effective in preventing pregnancies than TCu-380A IUD. Its efficacy is comparable to that of the Nova-T by two to three years of use; (b) the MLCu-250 IUD is similarly effective to TCu 200 but may be slightly less effective than TCu-220C; (c) no consistent differences were detectable in expulsion rates or in removal rates for bleeding/pain between the Multiload IUDs and comparative Copper-T IUDs; (d) the Multiload IUDs may perform better in nulliparous women than the T-shaped devices; (e) no or a very low incidence of uterine perforation is associated with insertions of the Multiload IUD; (f) ectopic pregnancy risks are similarly low in Multiload IUD users as in Copper-T-380A users; and (g) pelvic inflammatory disease (PID) risks are similarly low in Multiload IUD users as in users of T shaped copper IUDs. PMID- 1458889 TI - Risk factors for copper T IUD expulsion: an epidemiologic analysis. AB - Little is known of the factors associated with expulsion of intrauterine devices (IUD). We conducted a nested case-control study to examine the risk factors for copper T IUD expulsion using data from a multicenter international clinical trial. We included 70 cases with expulsion and 1,536 controls, and we examined a variety of characteristics of the IUD wearers. The proportional hazards model showed that young maternal age, abnormal amount of menstrual flow and dysmenorrhea before IUD insertion are risk factors for copper T IUD expulsion. The risk of expulsion steadily increased as age decreased, and as the severity of dysmenorrhea increased. PMID- 1458890 TI - What do women want during medical abortion? AB - A questionnaire study was carried out to investigate the needs of women undergoing a medical abortion induced by mifepristone in combination with either gemeprost pessaries or oral misoprostol. One-hundred-and-eighty women undergoing medical abortion of pregnancy of up to 63 days amenorrhoea were randomised to treatment in the sitting-room (treatment room) or in the ward. Overall, 77% and 69% treated in the sitting-room and ward, respectively, would have preferred treatment in the sitting-room. Fifty-four per cent did not wish their partner or friend to be present and 76% would prefer to stay in hospital following administration of prostaglandin. Ninety-five per cent of the patients would recommend this method of abortion to their friends. Women who received misoprostol required significantly less analgesia than women who were given 1 mg gemeprost as a vaginal pessary. The requirement for opiate analgesia was not influenced by parity, gestation of pregnancy, history of dysmenorrhoea or the dose of mifepristone. Almost 100% of the patients were satisfied with this method of treatment. This study indicates that the majority of women undergoing medical abortion prefer to be treated in a group, a method which is highly cost effective. PMID- 1458891 TI - Pharmacokinetics of levonorgestrel in 12 women who received a single oral dose of 0.15 mg levonorgestrel and, after a washout phase, the same dose during one treatment cycle. AB - The pharmacokinetics of levonorgestrel (LNG) was determined in 12 healthy women (age 21 to 33 years), following single dose administration of 0.15 mg LNG. The same preparation was also administered during one treatment cycle after a washout phase of 1 week. After single dose administration, maximum concentrations of LNG in the serum were 4.3 +/- 1.3 ng/ml. Post maximum drug levels declined biphasically with half-lives of 0.6 +/- 0.2 h and 13.9 +/- 3.2 h, respectively. The clearance was calculated to be 1.5 +/- 0.6 ml x min-1 x kg-1. The free fraction of LNG was 1.1 +/- 0.1% and the fractions bound to SHBG and albumin were 61.8 +/- 6.7% and 37.1 +/- 6.7%, respectively. There was a gradual decrease in serum trough levels of LNG from about 0.5 to 0.3 ng/ml during the cycle, and a concomitant decrease in SHBG concentrations in the serum by about 50%. Serum protein binding of LNG changed markedly during the treatment cycle. The free fraction increased to a value of 1.7 +/- 0.3%, the SHBG-bound fraction decreased to 42.0 +/- 11.4% and the albumin-bound fraction increased to 56.4 +/- 11.2%. Total serum clearance increased during the same time period from a mean value of 1.5 to about 2.5 ml x min-1 x kg-1. The clearance of unbound LNG, however, remained unchanged. An examination of the free LNG concentrations revealed the same time course of LNG trough levels during the cycle as the simulated curve. This was derived from the pharmacokinetic parameters which were obtained after single dose administration. Thus, the present study showed that the pharmacokinetics of LNG can be fully explained on the basis of single dose pharmacokinetics and the changes in serum protein binding which were caused by a reduction of SHBG levels in the serum during chronic treatment with LNG. PMID- 1458892 TI - Pharmacokinetics of levonorgestrel and ethinylestradiol in 9 women who received a low-dose oral contraceptive over a treatment period of 3 months and, after a wash out phase, a single oral administration of the same contraceptive formulation. AB - The pharmacokinetics of levonorgestrel (LNG) and ethinylestradiol (EE2) were determined in 9 healthy women (age 23 to 42 years), during a treatment period of three months with a low-dose oral contraceptive, containing 0.15 mg LNG together with 0.03 mg EE2 (Microgynon). After a wash-out period of 3 months, 8 of these women received a single administration of the same formulation. The results showed that there was an increase in serum trough levels of LNG, reaching steady state in the second half of each treatment cycle. The LNG levels achieved were about 3 to 4 times higher than anticipated on the basis of single dose administration. At the end of treatment cycles one and three, the terminal half life of LNG was in the range of 24-26 h, while a mean value of 20 h was observed following single dose administration. An EE2-induced increase in the SHBG concentration of about 50% as compared to pretreatment values was observed during a treatment cycle. Pretreatment values were reached following the drug-free interval of 7 days between two cycles. After single dose administration, the free fraction of LNG was 1.3 +/- 0.2% and the fractions bound to SHBG and albumin were 64.1 +/- 4.2% and 34.6 +/- 4.0%, respectively. Serum protein binding of LNG did not change during chronic treatment. An about 50% reduction in total and unbound clearance of LNG was observed during chronic treatment, as compared to single dose administration. Increased SHBG binding capacity and a reduced hepatic metabolic capacity were discussed as possible causes of accumulating LNG concentrations in the serum. On the last day of treatment cycles one and three, the AUC(0-24h) values of EE2 were 728 +/- 314 and 778 +/- 318 pg x ml-1 x h, respectively, and were in keeping with data reported from others. PMID- 1458893 TI - The FlexiGard 330 ICC, an ultrasound evaluation. AB - The FlexiGard 330 intrauterine copper contraceptive (ICC) was studied by ultrasound in 405 patients immediately following insertion and at each follow-up visit, for up to 5 years. The present study confirms the validity of the anchoring concept for the suspension of bioactive substances in the uterine cavity. The major conclusion from the study is that the anchor is non-migrating even when observed over a long period of time. Ultrasound examination is the method of choice to evaluate proper insertion technique as well as proper positioning of the device at follow-up. PMID- 1458894 TI - Clinical experience and pharmacological effects of an oral contraceptive containing 20 micrograms oestrogen. AB - The performance of a new low-dose oral contraceptive (Mercilon) containing only 20 micrograms ethinyloestradiol combined with 150 micrograms desogestrel is reviewed. Eight multicentre clinical trials have been completed and provide information on 10,672 women studied over 73,477 cycles. The high efficacy of Mercilon was indicated by the finding that only 10 pregnancies were reported; nine of these occurred in women who omitted to take Mercilon on a number of days and only one in a woman who took all the tablets according to instructions. Cycle control was good; as with all oral contraceptives, the incidence of breakthrough bleeding and spotting was highest in the first treatment cycle and by the sixth treatment cycle the values were usually < 5% and < 7%. More than 80% of women had regular cycles. Side effects were few, the most common being headache, nausea and breast tenderness with incidences in the sixth treatment cycle of less than 2%, 6% and 6%, respectively. There were no significant changes in body weight or blood pressure. Pharmacodynamic investigations showed no adverse effects. Only 1 of 5 studies found an increased response to a glucose tolerance test compared to the pretreatment test. In 8 of 10 studies, serum HDL-C concentrations increased on treatment and this was associated with increases in apoproteins A1 and A2. Serum triglyceride levels also increased but no change occurred in serum cholesterol or LDL-C levels. Haematological factors were assessed in 8 studies and only minor changes were observed. Serum binding protein (SHBG, CBG, caeruloplasmin) concentrations increased and serum androgen levels decreased. Measurements of blood FSH, LH, oestradiol and progesterone indicated adequate inhibition of ovulation. Mercilon is the only oral contraceptive containing 20 micrograms ethinyloestradiol to have high efficacy, to have no adverse pharmacodynamic effects and, importantly, to produce an acceptable bleeding pattern not significantly different from that of oral contraceptives with a higher content of ethinyloestradiol. PMID- 1458895 TI - Should we use prostaglandins, tents or progesterone antagonists for cervical ripening before first trimester abortion? AB - Sixty-four women requesting first trimester termination of pregnancy were recruited into a comparative cohort study comparing the cervical ripening properties of a mechanical dilator (Lamicel; n = 17), prostaglandin, antiprogesterone and placebo control (n = 15), gemeprost; n = 17) and mifepristone; n = 15). Compared to the placebo group, all 3 active agents dilated the cervix (p < 0.02) and they significantly reduced the force required to dilate it to 8 mm Hegar (p < 0.001). Although Lamicel insertion resulted in the largest pre-operative cervical dilatation all agents are effective. Therefore the cervical priming agent of choice should be the most convenient to use and the one with least side-effects. The oral antiprogesterone, Mifepristone, is the easiest to administer and has less side effects. PMID- 1458896 TI - Renal hypouricemia: classification, tubular defect and clinical consequences. PMID- 1458897 TI - Perspectives in acid-base balance in advanced chronic renal failure. PMID- 1458898 TI - Adverse events of subcutaneous recombinant human erythropoietin therapy. PMID- 1458899 TI - Recombinant human growth hormone in pubertal patients with chronic renal disease. PMID- 1458900 TI - Phagocytic function in the uremic patient. PMID- 1458901 TI - Blood-dialyzer interactions: their role in long-term complications of hemodialysis. PMID- 1458902 TI - Malnutrition in continuous ambulatory peritoneal dialysis and use of intraperitoneal amino acids. PMID- 1458903 TI - Lessons of peritoneal ultrastructure: from an inert dialyzing sheet to a living membrane. PMID- 1458904 TI - Vascular endothelin and renal disease progression. PMID- 1458905 TI - Lead and hypertension. PMID- 1458906 TI - Acquired cysts and neoplasms of the kidneys in renal allograft recipients. PMID- 1458907 TI - Calcium-dependent neutrophil activation. PMID- 1458908 TI - Altered cellular calcium metabolism in hypertension: a reassessment and a hypothesis. PMID- 1458909 TI - The metabolic acidosis of chronic renal failure: pathophysiology and treatment. PMID- 1458910 TI - pH homeostasis: the conceptual change. PMID- 1458911 TI - Whole body acid-base balance. PMID- 1458912 TI - Endothelium as a target for the immune injury in systemic vasculitis. PMID- 1458913 TI - Genetics of antiendothelial cell antibodies in systemic lupus erythematosus: the role of HLA-DP alleles. PMID- 1458914 TI - Effects of ANCA-positive sera on the generation of oxygen free radicals by neutrophils. PMID- 1458915 TI - Immunological monitoring in systemic lupus erythematosus. PMID- 1458916 TI - Lupus anticoagulants and antiphospholipid antibodies monitoring in systemic lupus erythematosus. PMID- 1458917 TI - Clinical implication of antiphospholipid antibodies in systemic lupus erythematosus. PMID- 1458918 TI - Intravenous cyclophosphamide pulse therapy in the treatment of systemic lupus erythematosus. Long-term results. PMID- 1458919 TI - Ciclosporin plus steroids versus steroids alone in the treatment of lupus nephritis. PMID- 1458920 TI - Treatment of the acute phase of lupus nephritis with 6-methylprednisolone pulses. PMID- 1458921 TI - Effects of intravenous cyclophosphamide in severe proliferative lupus glomerulonephritis. PMID- 1458922 TI - Vascular disease and thrombosis: relationship to the antiphospholipid antibodies. PMID- 1458923 TI - Antiphospholipid antibodies in patients with childhood onset systemic lupus erythematosus and their relatives. A French cooperative study. PMID- 1458924 TI - Lupus vasculitis. PMID- 1458925 TI - Approach to lupus nephritis based upon randomized trials. PMID- 1458926 TI - Treatment of diffuse proliferative lupus nephritis. PMID- 1458927 TI - Effects of corticosteroids on bone and blood pressure. PMID- 1458928 TI - Emerging techniques of investigation in the study of renal biopsies from patients with systemic lupus erythematosus. PMID- 1458929 TI - Significance of anticardiolipin and antiendothelial cell antibodies in the nephritis of lupus. PMID- 1458930 TI - Is renal vasculitis in patients with systemic lupus erythematosus a bad prognostic factor? PMID- 1458931 TI - Renal ultrastructural findings in lupus vasculopathies. PMID- 1458932 TI - Peculiar type of focal and segmental lupus glomerulitis: glomerulonephritis or vasculitis? PMID- 1458933 TI - Two cases of juvenile systemic lupus erythematosus with life-threatening central nervous system involvement: striking association with antiphospholipid antibodies. PMID- 1458934 TI - Quality improvement standards for intensive care unit monitors: we must be informed and involved. PMID- 1458935 TI - Advances in the acute therapy of hypertension. PMID- 1458936 TI - Neuroendocrine immunology: relevance to the management of critical illness. PMID- 1458937 TI - MD or not MD: is that the question? PMID- 1458938 TI - Postoperative hypertension: a multicenter, prospective, randomized comparison between intravenous nicardipine and sodium nitroprusside. AB - OBJECTIVE: To compare the efficacy and safety of iv nicardipine with sodium nitroprusside in the treatment of postoperative hypertension after both cardiac and noncardiac surgery. DESIGN: Multicenter, prospective, randomized, open-label study. SETTING: Six tertiary referral medical centers (recovery rooms and surgical ICUs). PATIENTS: A total of 139 patients with postoperative hypertension: i.v. nicardipine (n = 71), sodium nitroprusside (n = 68). INTERVENTION: Administration of i.v. nicardipine or sodium nitroprusside. MEASUREMENTS: Vital signs (BP, heart rate), hemodynamic variables, medication dosage, total number of dose changes, and time to achieve BP control were recorded. MAIN RESULTS: Both medications were equally effective in reducing BP in both the cardiac and noncardiac surgical groups. Under the conditions of the study, i.v. nicardipine controlled hypertension more rapidly than sodium nitroprusside (i.v. nicardipine 14.0 +/- 1.0 mins and sodium nitroprusside 30.4 +/- 3.5 mins, p = .0029). The total number of dose changes required to achieve therapeutic BP response was significantly less in the i.v. nicardipine-treated patients (i.v. nicardipine 1.5 +/- 0.2 vs. sodium nitroprusside 5.1 +/- 1.4, p < .05). Adverse effects were observed with both drugs (i.v. nicardipine 7% [5/71] and sodium nitroprusside 18% [12/68] [NS]). CONCLUSIONS: Intravenous nicardipine is as effective as sodium nitroprusside in the therapy of postoperative hypertension. Specific advantages have been identified. The use of i.v. nicardipine should be considered in the therapy of postoperative hypertension. PMID- 1458939 TI - Effects of dopamine on T-lymphocyte proliferative responses and serum prolactin concentrations in critically ill patients. AB - OBJECTIVES: Dopamine is currently used in the ICU for its vasopressor, renal vasodilating, and cardiac inotropic properties. Animal studies have shown both endocrine and T-lymphocyte alterations with dopamine agonist administration. The relationships between exogenous dopamine and patient hormonal and lymphocyte proliferative responses have not been evaluated in the critically ill patient. These findings furnished the impetus for the present study. DESIGN: Prospective, controlled, clinical study. PATIENTS AND METHODS: All patients admitted to the ICU at Truman Medical Center were evaluated for admission into the protocol, excluding patients whose medications or diseases produced effects in the study dependent variables. Before institution of dopamine therapy, blood samples were taken for T-cell analysis and prolactin measurement. Daily, early morning blood samples were taken if the dopamine infusion was > 5 micrograms/kg/min for 4 hrs during that 24-hr period. An early morning postdopamine sample was taken on the first day after dosage discontinuation. Control blood samples for determination of T-cell and prolactin responses were drawn from ICU patients who did not receive dopamine. A severity-of-disease score (Acute Physiology and Chronic Health Evaluation [APACHE II] score) was recorded for all patients. MAIN RESULTS: Serum prolactin concentrations decreased > 90% (p < .001) within hours in all patients receiving dopamine infusions at study dose limit or above. The in vitro T-cell proliferative response to concanavalin A decreased (a transitory response) in patients receiving a dopamine infusion (p < .001). Dopamine infusions in medical ICU patients produced an immediate and profound reduction in serum prolactin concentrations in both males and females. An immediate transitory decrease in patient T-cell response to concanavalin A stimulation in vitro was seen in patients receiving dopamine. CONCLUSIONS: The data suggest the possibility of altered endocrine and immune function as a corollary of therapeutic concentrations of dopamine in critically ill patients. PMID- 1458940 TI - Use of a combined right ventricular ejection fraction-oximetry catheter system for coronary bypass surgery. AB - OBJECTIVE: To evaluate the reproducibility and accuracy of a new pulmonary artery catheter system that provides both right ventricular ejection fraction and continuous venous oxygen saturation monitoring. DESIGN: Criterion standard study. SETTING: University medical center. PATIENTS: A consecutive sample of ten patients undergoing elective coronary artery bypass surgery provided informed consent for the study. Exclusion criteria included emergency surgery or clinically important preoperative tricuspid regurgitation as assessed by echocardiography. None of the patient sample was excluded. MEASUREMENTS: Catheter derived mixed venous and arterial oximetry data were compared with simultaneous values obtained using conventional laboratory cooximetry methods. Measurements were performed before cardiopulmonary bypass and intermittently up to 48 hrs after cardiopulmonary bypass. The variability of cardiac output and computed right ventricular ejection fraction was also assessed concurrently with the oximetry analysis. RESULTS: A significant correlation was observed for mixed venous oxygen saturation between catheter-derived and laboratory cooximetry data (r2 = .81, p < .01). Similarly, arterial oxygen saturation values obtained from pulse oximetry and laboratory values were significantly related (r2 = .81, p < .01). The coefficient of variation for each set of five repeated measurements for cardiac output was 8%, and for computed right ventricular ejection fraction, it was 16%. CONCLUSIONS: The combined catheter system provides the means to monitor both mixed venous oxygen saturation and right ventricular ejection fraction. These data provide a reliable and detailed assessment of cardiopulmonary function that should prove beneficial in the critical care setting. PMID- 1458941 TI - Can the need for a physician as part of the pediatric transport team be predicted? A prospective study. AB - OBJECTIVES: To evaluate the quality of objective information obtained during telephone requests for the transport of pediatric patients. To evaluate the ability of subjective judgment, the Pediatric Risk of Mortality (PRISM) score, and the presence of tachycardia for age to predict the need for a physician on as a member of the pediatric transport team. DESIGN: Prospective data collection. SETTING: The pediatric transport program of a children's hospital. PATIENTS: All 129 infants and children transported over a 4-month period. MEASUREMENTS AND MAIN RESULTS: We defined an objective measure of the need for a physician's presence during the transport of a pediatric patient, based on either the necessity for procedural or medical interventions during the time of transport or on direct admission to the pediatric ICU after transport. At the time of initial telephone contact, a physician's subjective opinion of the need for physician presence was recorded, a PRISM score was derived, and the presence of tachycardia (adjusted for age) was determined. Subsequently, the vital signs recorded on the record of this request were compared with those vital signs charted at the referring hospital at the time of the initial telephone request. A total of 96% of vital signs obtained during the initial telephone contact were consistent with those percentages in the referring hospital medical records. Fifty (39%) of 129 transported patients required procedural or medical interventions or pediatric ICU admission. Subjective judgments predicted physician need with a high sensitivity (0.98), but with a low specificity (0.18). PRISM score predicted 62 (48%) of 129 transports to be "physician-required" (sensitivity = 0.72; specificity = 0.67). There was no statistical association between tachycardia for age and the objective need for a physician's presence. CONCLUSIONS: Objective information obtained during request for transfer was reliable. At the time of request for transfer, subjective judgment, PRISM score, and the presence of tachycardia did not predict the need for a physician presence during transport. PMID- 1458942 TI - Pediatric risk of mortality scoring overestimates severity of illness in infants. AB - OBJECTIVE: To validate Pediatric Risk of Mortality (PRISM) scoring in infants and children admitted for intensive care. DESIGN: Validation cohort. SETTING: A five bed pediatric ICU and three cots providing intensive care for surgical neonates, within a 159-bed tertiary care children's hospital. PATIENTS: All patients admitted for intensive care during an 18-month period, January 1990 to July 1991. METHODS: Admission (first 24 hrs) PRISM scoring was introduced as a routine procedure. Discretion was allowed in requesting arterial blood gas measurements and clotting studies. All other parameters were intended to be measured on all patients. MEASUREMENTS AND MAIN RESULTS: PRISM scores were obtained on 380 (88%) of 433 patients. Median age was 15 months. A complete PRISM score was obtained in 24% of cases and a score as intended (i.e., allowing discretionary omissions) was obtained in 56% of patients. Comparison of observed and predicted mortality rates using chi square goodness-of-fit tests showed a significantly better observed outcome for all patients (chi 2(5) = 12.04, p < .05). In-depth analysis indicates that the model works well for children (chi 2(5) = 1.80, p > .75), but that observed outcome is significantly better than predicted for infants (chi 2(5) = 17.46, p < .01). Underscoring of children is not the cause of this finding. CONCLUSIONS: In our center, PRISM scoring overestimates severity of illness in infants. PRISM scoring is not institutionally independent and therefore, at present, a comparison between units may not be justified. A reappraisal of the parameter ranges for infants is suggested. PMID- 1458943 TI - Intensive care unit outcome in the very elderly. AB - OBJECTIVES: To determine if age, previous functional status, or acute severity of illness affect the acute and long-term mortality rates and functional status of the very elderly (> or = 85 yrs) after an ICU admission. DESIGN: Cohort study (retrospective entry for the first year of the study and prospective entry thereafter with prospective follow-up throughout). SETTING: An ICU in a community teaching hospital with follow-up at home or at a skilled nursing facility. PATIENTS: All (n = 105) patients > or = 85 yrs admitted to the ICU over a 2-yr period. MAIN OUTCOME MEASURES: ICU, 30-day posthospital discharge, and 1-yr mortality rates, activities of daily living scores, organ system failure score at the time of ICU admission. RESULTS: The ICU, 30-day posthospital discharge, and the 1-yr mortality rates were 30%, 43%, and 64%, respectively. Mortality rates significantly increased between the ICU stay or 30 days posthospital discharge and 1-yr follow-up periods. Of those patients who lived up to 6 months after hospital discharge, 86% survived to 1 yr with little change in functional status from baseline. In the patients with > or = 2 organ system failures, there were 88% 30-day posthospital discharge and 100% 1-yr mortality rates. Severity of illness, as measured by the number of organ system failures, was associated with increased ICU (odds ratio 3.38; 95% confidence interval, 1.51 to 7.60; p < .005) and 1 yr (odds ratio 5.76; 95% confidence interval, 2.49 to 13.29; p < .0001) mortality rates, while age within this group and preadmission functional status were not. CONCLUSIONS: Within the very elderly population, acute severity of illness is the most significant predictor of mortality after an ICU admission. For most very elderly patients, surviving 1 yr after an ICU admission, there is little change in functional status. PMID- 1458945 TI - Alterations in oropharyngeal flora in patients with a nasogastric tube: a cohort study. AB - OBJECTIVE: To determine whether or not the presence of a nasogastric tube causes a change in the bacterial flora in the oropharynx. STUDY DESIGN: Cohort (prospective) design with concurrent control. SETTING: General Surgical and Ear, Nose, and Throat Units of a tertiary care hospital. PATIENTS: Sixteen patients with and 14 patients without a nasogastric tube. INTERVENTIONS: Patients scheduled to undergo surgery under general anesthesia with endotracheal intubation were eligible for inclusion in the study. From these patients, a study cohort of 16 consecutive patients who were to have nasogastric tube intubation and 14 patients who were not to have nasogastric intubation were enrolled. All patients had a high oropharyngeal swab taken for bacteriologic culture just before surgery. The swab of the oropharynx for culture was repeated after 48 to 72 hrs. The type of organism grown was identified and compared between and within the two groups. RESULTS: There was a significant increase in the frequency of colonization of the oropharynx by pathogenic Gram-negative bacteria after 48 to 72 hrs of nasogastric intubation in comparison with the preintubation level (p < .01) as well as in comparison with the group that did not have nasogastric intubation (p < .001). The pathogens included Pseudomonas, Klebsiella, Proteus and Escherichia coli. There was also a tendency for suppression of normal flora. There was no significant change in the flora of the control group of patients who did not have nasogastric intubation. The two groups were comparable with respect to age, gender, severity of underlying illness, and use of prophylactic perioperative antibiotics. CONCLUSIONS: The presence of nasogastric tubes in patients predisposes to colonization by Gram-negative pathogenic bacteria within 48 to 72 hrs. PMID- 1458944 TI - Acute continuous hemofiltration with dialysis: effect on insulin concentrations and glycemic control in critically ill patients. AB - OBJECTIVES: To quantitate insulin losses and glucose absorption during acute continuous hemofiltration with dialysis and to assess the clinical importance of these changes. DESIGN: Prospective collection of serum and ultradiafiltrate fluid in patients receiving acute continuous hemofiltration with dialysis. Measurements of serum and ultradiafiltrate insulin and glucose concentrations. Calculations of insulin excretion and glucose absorption. Correlation of findings with patient outcome. SETTING: University medical center. PATIENTS: Sixteen ICU patients with acute renal failure. MEASUREMENTS AND MAIN RESULTS: The mean serum glucose concentration before acute continuous hemofiltration with dialysis was 178 mg/dL (9.9 mmol/L) (95% confidence interval 112 to 244 mg/dL [6.2 to 13.6 mmol/L]), increasing to 257 mg/dL (14.3 mmol/L) (95% confidence interval 167 to 347 mg/dL [9.3 to 19.3 mmol/L]) after 4 hrs of acute continuous hemofiltration with dialysis, and stabilizing at 207 mg/dL (11.5 mmol/L) (95% confidence interval 160 to 254 mg/dL [8.9 to 14.1 mmol/L]) at 24 hrs. Mean plasma insulin concentration before acute continuous hemofiltration with dialysis was 34.4 mU/L (95% confidence interval 8.6 to 60.2 mU/L), increasing to 54.4 mU/L at 4 hrs (95% confidence interval 25 to 83.8 mU/L; NS). There was no significant decrease in mean insulin concentration across the filter (51.8 mU/L before filtration vs. 51.9 mU/L after filtration). Insulin was detected in the ultradiafiltrate but its overall mean clearance rate was only 6.2 mL/min, with mean daily losses of 689 mU/day (95% confidence interval 325 to 1053 mU/day). During acute continuous hemofiltration with dialysis, glucose absorption through the filter averaged 134 g/day (95% confidence interval 96.2 to 171.8 g/day). Plasma insulin concentrations were significantly (p < .05) lower in survivors than nonsurvivors (51.7 vs. 123.6 mU/L). CONCLUSIONS: Significant glucose absorption occurs during acute continuous hemofiltration with dialysis and is coupled with minor insulin losses (< 1 U/day) through the filter. These events do not appear to have major clinical impact. A low plasma insulin concentration is associated with diminished mortality rates in this group of patients. PMID- 1458946 TI - Evaluation of the consistency of Acute Physiology and Chronic Health Evaluation (APACHE II) scoring in a surgical intensive care unit. AB - OBJECTIVES: To determine the applicability of the Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system in a Swiss ICU, and to evaluate its utility in evaluating data from 2 yrs of consecutive admissions to show that the predictability of outcome is similar to that predictability observed by Knaus et al. in 1985 (in 5,815 patients), with the provision that large numbers of patients are studied. DESIGN: Prospective clinical trial over 2 yrs, with statistical analysis of the Swiss patients, and between the Swiss patients and the patients studied by Knaus et al. Receiver operating characteristic curves were calculated. SETTING: Surgical ICU in a Swiss university hospital. PATIENTS: A total of 2,061 consecutive patients admitted to the surgical ICU who were classified as postoperative (elective or emergency) and nonoperative. Hospital mortality rate was considered. RESULTS: Patients were 53 +/- 16 yrs of age. Mean APACHE II score was 10.5 +/- 7.0. The mean APACHE II score was significantly (p < .001) lower in the 1,813 survivors (9.0 +/- 5.2) than in the 248 nonsurvivors (21.5 +/- 8.5). The mortality rate was higher among the Swiss patients when compared with the patients studied by Knaus et al. who had postoperative scores of 20 to 29 and nonoperative scores of > 24. The distribution of the scores and mortality rates were stable during the two study periods, as were the differences in mortality rates between the Swiss population and that population studied by Knaus et al. Sensitivity and specificity of the scores were highest in the emergency surgery group (87% and 78%), and lowest in the elective surgery group (76% and 73%). The APACHE equation underestimated the risk of death. CONCLUSIONS: The APACHE II score, because of its consistency over time and the stability of the mortality rates, can be used in our surgical ICU without modification. The calculated risk of death gives no additional information. PMID- 1458947 TI - Prospective evaluation of residents and nurses as severity score data collectors. AB - OBJECTIVES: To determine the interobserver reliability of residents and nurses collecting Acute Physiology and Chronic Health Evaluation (APACHE II) data and the subsequent effect of these data collections on individual patient mortality prediction. DESIGN: In a prospective study, residents and nurses independently collected data to derive APACHE II scores. When their scores differed, a standard score was determined by one of the investigators. SETTING: A general medical and surgical ICU. PATIENTS: A total of 120 consecutive patients were included; of these patients, 79 had standard scores determined because resident and nurse scores differed. MAIN RESULTS: There was overall agreement between the residents and nurses with no significant difference between mean APACHE II scores or mean predicted mortality rates. Intraclass correlation coefficients confirmed good overall agreement between observer groups for predicted mortality rate: resident vs. nurse r2 = .94, resident vs. standard r2 = .94, and nurse vs. standard r2 = .90. However, clinically significant lack of agreement was demonstrated in 5% of the patients by the 95% confidence limits of agreement: resident vs. nurse -14 to +14%, resident vs. standard -10 to +14%, and nurse vs. standard -14 to +20%. CONCLUSIONS: While interobserver variability between resident and nurse data collection has minimal effect on derived predicted mortality rate with large patient groups, significant variability may occur in individual patients. Residents were more accurate data collectors than nurses. PMID- 1458948 TI - High-dose magnesium sulfate attenuates pulmonary oxygen toxicity. AB - BACKGROUND AND METHODS: Rats rapidly develop respiratory distress when exposed to 100% oxygen and die within a few days. Autopsy of the lung shows severe histologic damage characteristic of the adult respiratory distress syndrome. The purpose of this study was to evaluate the effects of magnesium sulfate loading in a rat model of acute oxygen toxicity. Thirty-four rats were divided into three groups. Group 1 (n = 18) served as a control (no magnesium therapy), while group 2 (n = 8) and group 3 (n = 8) received varying amounts of magnesium sulfate. All animals were exposed to 100% oxygen for 96 hrs or until death. Lung damage was quantitated by measuring the lung injury score on histologic examination. RESULTS: Administering magnesium sulfate in moderate doses at infrequent intervals to rats (group 2) resulted in less severe oxygen-induced lung damage than that which occurred in rats not receiving magnesium (control group). However, the difference was not statistically significant. Rats (group 3) given doses of magnesium sulfate in amount and frequency adequate to maintain a serum magnesium concentration recognized as therapeutic in eclampsia significantly reduced oxygen-induced lung damage. CONCLUSION: High-dose magnesium sulfate therapy can reduce lung injury caused by acute oxygen toxicity in rats. PMID- 1458949 TI - Selective decontamination of the digestive tract prevents secondary infection of the abdominal cavity, and endotoxemia and mortality in sterile peritonitis in laboratory rats. AB - BACKGROUND AND METHODS: This study was undertaken to find out whether translocation of bacteria to the abdominal cavity and endotoxemia in rats with sterile peritonitis could be prevented by selective decontamination of the digestive tract. Sterile peritonitis was caused by the intraperitoneal injection of either 100, 150, 200, or 300 mg of zymosan suspended in paraffin. RESULTS: The frequency of infection of the abdominal cavity depended on the dose of zymosan given, ranging from 20% in rats receiving 100 mg to 89% in rats receiving 300 mg of zymosan. In rats not receiving antibiotics for selective decontamination of the digestive tract (the control group). Gram-negative bacilli were isolated from the digestive tract in all rats, and Gram-negative bacilli were isolated from the abdominal cavity in ten of 19 rats. In rats receiving antibiotics for selective decontamination of the digestive tract, Gram-negative bacilli were isolated from the digestive tract in none of the 14 rats, and likewise, Gram-negative bacilli were isolated from the abdominal cavity in none of the 14 rats (p < .005). Moreover, in rats receiving antibiotics for selective decontamination of the digestive tract, endotoxin levels in feces and plasma were significantly lower, as compared with rats not receiving antibiotics for selective decontamination of the digestive tract. CONCLUSION: Selective decontamination of the digestive tract prevents translocation of Gram-negative bacilli to the abdominal cavity, and endotoxemia and mortality in rats with sterile peritonitis. PMID- 1458951 TI - Critical care: how should we evaluate our progress? AB - OBJECTIVE: Review of the history and accomplishments of the Society of Critical Care Medicine (SCCM) to determine appropriate directions for the future. DATA SOURCES: Historical documents of the SCCM, Critical Care Medicine, bioethics and healthcare financing literature, Instant Library of Quotations. STUDY SELECTION: Identified (by the author) material containing specific statements concerning goals and objectives at the time of the founding of the SCCM and at intervals. Material supporting and criticizing predictive indices were identified and bioethical treatises concerning patient autonomy and quality-of-life decisions were chosen. DATA EXTRACTION: Presidential addresses of the first three SCCM presidents, material relevant to preservation of life and alleviation of suffering from bioethical and healthcare financing perspectives. Relevant quotations. DATA SYNTHESIS: Initial goals and objectives were identified. Societal and economic factors changing critical care were analyzed for their effect on current and future SCCM directions and objectives. CONCLUSIONS: The founding members set important goals for critical care and patient care, research, education, and organization. From a perspective of what was foreseeable, these goals have been accomplished to an admirable degree. The SCCM has responded to these goals by providing educational programs and fostering research, especially in its annual meetings and through the publication of guidelines in Critical Care Medicine. The SCCM members would do well to read the first three presidential addresses to experience the eloquence and foresight firsthand, particularly with respect to the founders' spirit, considerations of training, scope of care, humanism, organization and relations within and outside of critical care, integration of care, and development of the scientific process at the bedside. There have been major changes in society since the SCCM was founded: the maturation of the concept of patient's autonomy; recognition of quality-of-life values; healthcare financing; and legal and ethical aspects of care. The critical care profession in general, and the SCCM specifically, should seek to develop effective cost-containment strategies and severity of illness or predictive indices. The SCCM should also educate the professions with respect to ethical issues and provide information directly to the public, especially in the areas of advance directives and withholding and withdrawing care. Through these contributions, the SCCM can assume its proper leadership role within medicine, but, of greater importance, in society. In doing so, societal myths and misunderstandings of the capabilities, futility, role, and limitations of critical care can be corrected. The organization and structure of the SCCM are well developed to accomplish these ends. The SCCM leaders are both able and willing. The objectives seem reasonable and should be attainable. PMID- 1458950 TI - Rethinking brain death. AB - OBJECTIVE: To evaluate whether current criteria for the diagnosis of brain death fulfill the requirement for the "irreversible cessation of all functions of the entire brain, including the brainstem." DATA SOURCES: Clinical, philosophical, legal, and public policy literature on the subject of brain death. DATA EXTRACTION/SYNTHESIS: We advance four arguments to support the view that patients who meet the current clinical criteria for brain death do not necessarily have the irreversible loss of all brain function. First, many clinically brain-dead patients maintain hypothalamic-endocrine function. Second, many maintain cerebral electrical activity. Third, some retain evidence of environmental responsiveness. Fourth, the brain is physiologically defined as the central nervous system, and many clinically brain-dead patients retain central nervous system activity in the form of spinal reflexes. We explore options for resolving these inconsistencies between the conceptual definition and the clinical criteria used to make the diagnosis of brain death. CONCLUSIONS: Brain death is a valid conception of death because it signifies the permanent loss of consciousness. Brain death criteria should therefore be based on the diagnosis of the permanent loss of consciousness rather than that of the loss of vegetative brain functions. Revision of our current "whole brain" definition of brain death to a "higher brain" standard should be considered. PMID- 1458952 TI - Control of massive hemoptysis by endobronchial tamponade with a pulmonary artery balloon catheter. PMID- 1458953 TI - Seizures after flumazenil administration in a case of combined benzodiazepine and tricyclic antidepressant overdose. PMID- 1458954 TI - Alterations in anion gap following cardiopulmonary bypass. PMID- 1458955 TI - Acute physiology and chronic health evaluation and Glasgow coma scores. PMID- 1458956 TI - Usefulness of an Antireflux valve in the intensive care unit. PMID- 1458957 TI - Conflicts over ethical principles in the intensive care unit. PMID- 1458958 TI - The emperor's new clothes. PMID- 1458959 TI - Interventional chest radiology. AB - Radiologically guided percutaneous drainage procedures are commonly performed to manage a variety of intrathoracic collections. As a natural extension of similar procedures performed for abdominal and pelvic collections, these procedures use both the conventional and cross-sectional imaging modalities to detect intrathoracic collections and to guide safe percutaneous diagnostic aspiration and drainage. The high-resolution images obtainable on current computed tomographic and ultrasound units allow detection of lung abscesses, empyemas, malignant effusions, and infected mediastinal fluid collections that are amenable to percutaneous drainage. Advances in catheter design and introduction techniques have allowed drainage of collections previously managed by open procedures. The ease of fluoroscopically guided catheter placement for treatment of spontaneous or biopsy-induced pneumothorax has provided a safe, effective, and comfortable alternative to blind large-bore surgical tube placement. Transthoracic needle biopsy of lung, mediastinal, and pleural or chest-wall masses has resulted from the availability of image intensifiers and cross-sectional imaging modalities useful in guiding needle placement and tissue sampling. Equally important has been the development of cytopathology as a subspecialty that can provide diagnoses of malignant and benign thoracic conditions from needle aspirates. This technique has had a major impact on the preoperative evaluation of the patient with a solitary pulmonary nodule and has eliminated unnecessary surgery in a significant percentage of such patients. Transcatheter arterial embolization has made a significant contribution to the management of the patient with massive hemoptysis and is the procedure of choice for treatment of pulmonary arteriovenous malformations. A thorough knowledge of the vascular anatomy of the thorax and expertise in catheterization and embolization techniques are prerequisites for the safe performance of these procedures. PMID- 1458960 TI - Behavioral treatment of drug exposed infants: analyzing and treating aggression. PMID- 1458962 TI - Strive for earlier diagnosis and treatment of hilar bile duct carcinoma. PMID- 1458961 TI - Nutrition and Head Start. PMID- 1458963 TI - Extrahepatic bile duct cancer. Report of 106 cases. AB - Extrahepatic bile duct cancers (BDC) are still frustratingly difficult lesions to deal with at present. 106 cases of BDC treated between January 1986 and December 1990 were reviewed retrospectively. The resectability rate of the entire series was 18.9%. Hilar (upper third) BDC accounted for 51% of the entire series and its resection rate was 14.8%. Lymph node metastases occurred in 40.9% of the cases and were mostly seen in the middle 1/3 of BDC. 32% of the cases had liver metastases, frequently occurred in hilar BDC. Sixty-four patients had specimens histologically studied. Of them, adenocarcinomas accounted for 90.6% (58 cases) and adenosquamous carcinomas 4.7% (3). Among the adenocarcinomas, 32 (55.2%) cases were well differentiated and 26 (44.8%) poorly differentiated. PMID- 1458964 TI - Extracorporeal shock wave lithotripsy and methyl tert-butyl ether for gallbladder stones. AB - Twenty-one patients with gallbladder stones of 1.1-2.6 cm in diameter were treated by extracorporeal shock wave lithotripsy (ESWL) combined with dissolution using methyl tert-butyl ether (MTBE). In 18 of 21 patients, ESWLs were followed by MTBE instillation through a catheter placed percutaneously via the liver and the gallbladder bed under ultrasonographic and fluoroscopic guidance. As a result, 15 of the 18 patients were cleared of their stones after 54 minutes to 3 hours of dissolution. In the other three cases initially treated by MTBE, ESWLs were added because of no dissolution or poor efficacy. Consequently, after additional 3-5 hours of instillation, complete dissolution in one and subtotal dissolution in two were achieved. Our preliminary results indicated that ESWL followed by MTBE dissolution in the management of cholesterol gallbladder stones was reasonable. On the one hand, ESWL can enhance dissolution by increasing the surface area of stone, and on the other hand MTBE can instantly clear the fragments created by ESWL, so that long-term bile acid intake and potential side effects caused by fragment migration might be avoided. PMID- 1458965 TI - Surgical treatment of hilar bile duct carcinoma. Clinical and pathological studies. AB - Resection of the extrahepatic bile tract for hilar bile duct carcinoma was performed at the PLA General Hospital, with a resectability rate of 62% (31/50) and no operative mortality. Hepatic lobectomy was performed at the same time in 16 cases (51.6%). Reoperative resections were successfully done in 5 cases; 4 cases are still living 1-4 years after the second operation. The cause of late death was mainly biliary infection due to local recurrence and bile duct obstruction. The median survival period was 15 months. 32 cases were studied pathologically, of which 27 were resected surgical specimens and 5 autopsies. The tumors were histologically classified into 4 types: papillary adenocarcinoma (6 cases); well differentiated adenocarcinoma (21); poorly differentiated adenocarcinoma (3); and simple carcinoma (2). The importance of early diagnosis of hilar bile duct carcinoma at its subclinical stage before appearance of clinical jaundice is stressed. PMID- 1458966 TI - Role of monoconjugated bilirubin in pathogenesis of gallstones. AB - In order to explore the substantial role of monoconjugated bilirubin (MCB) in gallstone formation, bile pigment precipitation and hemolytic jaundice, three experimental protocols have been studied, namely, (1) MCB and dietary induced pigment gallstone model, (2) MCB in human gallstone and incubated bile precipitates and (3) MCB in hemolytic jaundice. It was found that doubly increased MCB accounted for 1/3 of the total pigment in lithogenic guinea pig and CDCA plus glycine possessed certain protective effect from gallstone development; MCB was found in human gallstones both in bilirubinate and cholesterol type, and an unknown pigment, possibly an isomer of MCB, was found in black stone. During experimental hemolytic jaundice model preparation, both MCB and UCB were elevated, and MCB was found increased by 10 times, even exceeding the concentration of DCB when the injected bilirubin was about 4 mg/kg of body weight. It is reasonable to consider that MCB as a coprecipitant with UCB and a precursor of UCB played an essential role in the pathogenesis of gallstones. PMID- 1458967 TI - Effects of glutathione depletion using buthionine sulphoximine on the cytotoxicity in mammalian cells and human tumor cells in vitro. AB - An inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO), was used to deplete the endogenous thiols in mammalian cells in vitro. In this study, the cytotoxicity of BSO and BSO combined with the hypoxic cell radiosensitizer misonidazole (MISO) was investigated. Both aerobic and hypoxic cytotoxicity of MISO was found to be increased. The concentration of BSO required to reduce the colony forming ability to 50% (Cc) for the chronic cytotoxicity on V79 cells was 0.03 mmol/L under aerobic condition, while the Cc for the acute cytotoxicity on V79 cells under hypoxic and aerobic conditions was 0.4 and 0.5 mmol/L. The growth inhibition rate of human tumor cells K562 and SGC-7901 by BSO was 6.89-26.06% and 12.01-55.69%, respectively. Enhanced cytotoxicity activity was observed when BSO was used in combination with cis-dichlorodiamino Pt(II) or 5-fluorouracil. PMID- 1458968 TI - Optimal low dosage of acetylsalicylic acid (ASA) for the prevention and treatment of ischemic cerebrovascular disease in geriatric patients. AB - A series of 108 geriatric patients with ischemic cerebrovascular disease were treated with low dose aspirin (acetylsalicylic acid, ASA). Daily doses of 100 mg, 50 mg and 25 mg were administered to three groups of 36 patients. Changes in platelet aggregation responses were dynamically observed in 64 (22 normal subjects, 42 patients). Monitoring of 22 normal subjects revealed inhibition of platelet aggregation at a dose of 300 mg or 100 mg which could last as long as 7 days. This suggests that 100 mg or less could be clinically effective. Satisfactory inhibitory effects on platelet aggregation were observed in all three groups, with 14 patients in each group given daily doses of 100 mg, 50 mg and 25 mg during four weeks' observation. The most effective inhibition was obtained in the 50 mg group. Therefore, the authors recommend 50 mg/d as the optimal dosage for low dose aspirin therapy in geriatric patients. PMID- 1458969 TI - Value of CT myelography in differential diagnosis of spinal extradural tumors. AB - Twenty-three cases of spinal extradural tumors were differentiated with CT myelography. In 16 benign tumors, the proximal and/or distal widened extradural space was filled with adipose tissue, whereas in 7 malignant tumors, the widened extradural space showed soft-tissue density. This difference is helpful in evaluating the nature of the tumors. PMID- 1458971 TI - Effect of heparin on the anionic sites of glomerular basement membrane in adriamycin nephrosis in rats. AB - The effect of heparin on the anionic sites of glomerular basement membrane (GBM) in adriamycin-induced nephrotic rats was studied by means of calculating the polyethyleneimine (PEI) stained particles under electron microscope. The results showed that treatment with heparin under the anticoagulant effect markedly reduced the loss of anionic sites within lamina rara externa (LRE) of GBM and also the urinary protein excretion in nephrotic rats. The results demonstrated that one of the mechanisms of heparin in preventing the structural damage of glomeruli in kidney diseases was the reduction of the loss of anionic sites within LRE, indicating that changes in biomembrane charge played an important role in the pathogenesis of nephrotic syndrome. The results provided a scientific basis for the use of heparin to treat glomerular diseases. PMID- 1458970 TI - Anisodamine inhibits acetylcholine-induced endothelium-dependent relaxation of canine femoral artery. AB - The effects of anisodamine on acetylcholine-induced endothelium-dependent relaxation were studied in organ chambers and under bioassay conditions. In organ chamber experiments, both acetylcholine and bradykinin induced an endothelium dependent relaxation of norepinephrine-contracted canine femoral arteries in a concentration-dependent manner; the relaxation induced by acetylcholine, but not that by bradykinin, was inhibited by anisodamine or atropine in a concentration dependent manner. In bioassay experiments, a denuded ring of left circumflex coronary artery was superfused with perfusate passed through segment of femoral artery with endothelium or a direct superfusion line. Acetylcholine induced the release of relaxing factor(s) from the segment with endothelium causing a relaxation of bioassay ring and the relaxation was eliminated by anisodamine infused into the perfusion line above, but not below, the perfused segment. The results suggest that anisodamine, like atropine, is able to inhibit acetylcholine induced endothelium-dependent relaxation by blocking endothelial muscarinic receptors which activate the release of endothelium-derived relaxing factor(s). PMID- 1458972 TI - Hepatic stimulator substance from human fetal liver for treatment of experimental hepatic failure. AB - The authors previously reported the successful reversal of lethal D-Gal induced hepatic necrosis in rats by human hepatic stimulator substance (hHSS), a liver specific growth factor partially purified from human fetal liver cells, which promoted hepatocyte proliferation. In this study, they further investigated the mechanism of hHSS in improving survival of experimental acute hepatic failure. Our results demonstrated that the level of alanine transaminase and endotoxin in the plasma and lipid peroxides in the liver of chemically poisoned rats were reduced by hHSS to different extent at different periods of observation compared with the saline control group. The apparent recovery of liver function and the increase of 3H-TdR incorporation into hepatic DNA correlated with the morphologic changes observed under light and electron microscopes, showing that the damages inflicted on the cellular and subcellular structure in the liver of hHSS-treated rats were greatly alleviated and rapidly repaired. Therefore, hHSS, which can prevent liver deterioration and promote hepatocyte regeneration, may be a new hepatic stimulator factor readily available for clinical use. PMID- 1458973 TI - Changes in hepatic energy metabolism in experimental acute pancreatitis. AB - The changes in the cellular concentrations of ATP, ADP, AMP and oxidative phosphorylation of mitochondria in the liver were investigated experimentally in rats with acute pancreatitis (AP). The energy charge (ATP + 1/2ADP)/(ATP+ ADP+ AMP) of the liver decreased from 0.866 to 0.806 (P < 0.05) at 24 hours after onset of AP, and continuously decreased to 0.769 (P < 0.01) at 48 hours. On the other hand, the mitochondrial phosphorylative activity increased rapidly to 130% and 157% in the controls at 12 hours and 24 hours respectively and then decreased rapidly at 48 hours. The blood ketone body ratios were paralleled to the hepatic energy charge level in AP rats. These findings suggest that the nature of the derangement of the hepatic energy metabolism initiated by AP is that the effects of mitochondria damage result in a significant decrease in liver energy charge level, leading ultimately to hepatocellular impairment, and the measurement of the blood ketone body ratio is useful in evaluating the energy status of the liver in AP patients. PMID- 1458974 TI - Prevention of blindness in China. PMID- 1458975 TI - [A hospital medical director on the "structure regulation"--outline. Open letter to the federal administrator of public health]. PMID- 1458976 TI - [The physician (surgeon) as an expert witness in the court room]. PMID- 1458977 TI - [Expert information in radiation protection. Cost of courses in radiation protection]. PMID- 1458978 TI - [Surgery is a craft, a science and an art. In memory of E. Lexer on his 125th birthday 22 May 1992]. PMID- 1458979 TI - [Letter to G. Aumann, "Experiences in ambulatory surgery: Anesthesia techniques"]. PMID- 1458980 TI - [Letter to T. A. Angerpointner, "Ambulatory surgery--indications, results and limits"]. PMID- 1458981 TI - [Indications and technique of osteosynthesis in injuries of the cervical vertebrae]. PMID- 1458982 TI - [Ventral stabilization in the area of the thoracic and lumbar spine]. PMID- 1458983 TI - [Transpedicular spondylodesis of injuries of the thoracic and lumbar spine]. PMID- 1458984 TI - [New aspects in anterior plate osteosynthesis of injuries of the cervical spine]. PMID- 1458985 TI - [Indications for surgical therapy of sacral fractures]. PMID- 1458986 TI - [Surgical therapy of bone metastases of the upper and lower extremity]. PMID- 1458987 TI - [Skeletal metastases in the area of the pelvis]. PMID- 1458988 TI - [Continuously alternating prone and supine positioning in acute lung failure]. AB - Acute respiratory failure is still one the main problems in surgical intensive care. Unknown pathophysiological mechanisms permit only symptomatic therapy. Today ventilatory strategies by using PEEP und IRV are established to improve gas exchange and FRC by recruiting collapsed alveoli, decreasing intrapulmonary shunting and returning V/Q matching to normal. Furthermore different studies have shown the effects of supine and lateral decubitus posture in patients with acute respiratory failure. There are only rare reports on using the prone position, which doesn't require two-lung ventilation in difference to lateral position. We have studied 16 patients with acute respiratory failure by using continuous changing between prone and supine position under mechanical ventilation. All were male, aged 41.3 years in the middle and showed an average "Injury Severity Score" of 30 (13-50). 15 were trauma patients with blunt chest trauma in 11 cases. We have used prone position on threatening or manifest ARDS. In all patients we observed an increment of PaO2 during prone position on to 48 mmHg so that FiO2 could be reduced on an average of 0.2 within the first 48 h since changing patient's position. Posture changing depends on blood gas analysis, specifically on decreasing PaO2 after previous increment. Patients remained in prone and supine position at a mean of 6.3 (4.5-20) h and posture changing was proceeded over a period of 15.4 (7-32) days. No problems recording to blood pressure or mechanical ventilation appeared during prone position. 11 of 16 patients survived (68.8%), 5 died of cardiac (2) and multi organic failure (3) in connection with sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1458989 TI - [Use of internal fixator in injuries of the thoracic and lumbar spine]. AB - Between 1984 and 1989 51 patients with spinal traumata received surgical treatment by means of Fixateur interne. The results of patients' postsurgical check-up were as follows: Cases with incomplete neurological dysfunctions (levels Frankel B-D)-especially lumbar-showed improvements of neurological deficiencies up to three levels Frankel after emergency decompression and stabilization. The majority of cases with complete paraplegia-especially thoracic-did not subside. This holds true even for the results of a second check-up after about three years. A correlation between the degree of stenosis of the spinal canal and the neurological dysfunctions could not be established. The results of segmental stabilization by means of internal fixator and of definitive spondylodesis by means of autogenous spongiosa were positive, as was the spine proof and the patients' postsurgical function. PMID- 1458990 TI - [External fixator in complicated tibial fracture. Effect of various fixation systems on fracture healing and rate of complications]. AB - In a retrospective analysis 93 external fixations with different rigidity after open tibial shaft fractures have been reviewed and compared concerning complications and healing time. Fracture consolidation was attained in fixation with unilateral frame after 14 weeks, with bilateral v-shaped fixator after 19 weeks and with triangular configuration in about 28 weeks. Subsequent internal fixation or extension to v-shaped fixation was necessary in about 33% after initial unilateral half-pin frame, whereas 90% of the two rigid systems could be left in situ until fracture consolidation was achieved. Cancellous bone grafts were performed in 58% after triangular, in 40% after v-shaped, and 28% after unilateral fixation. Pin infections were observed in 36% after triangular, 25% after bilateral v-shaped, and in 15% after unilateral fixation. PMID- 1458991 TI - [Histologic reactions of the bone-implant zone and cortical bone area after long term hip replacement]. AB - 29 femora with cemented hip endoprostheses and 17 age related controls were analyzed regarding different histological criteria. All specimens were processed to undecalcified ultra thin grindings and in addition a few to surface stained block-grindings. The reactions at the bone implant interface in cases without loosening of the implant are: accumulation of macrophages and multinucleated giant cells, fibrous tissue membranes with a mean thickness of 103 microns and mineralization defects near the cement. The mean rate of direct bone/bone-cement contact is 2.7% of the whole cement surface. The phenomenons at the interface were explained as being the result of micromovement and resulting from wear and tear. The cortical bone demonstrates a remarkable loss of bone (up to 60% after 12 years) following an increase of osteoclastic resorption with no change of osteoblast activity. The localization of the bone loss indicates a relation to the new load situation after implantation. PMID- 1458992 TI - [Defect coverage of the extremities with distal pedicled flap-plasty]. AB - Clinical consideration of anatomy of skin vascularity led to the establishment of distally pedicled flaps in the extremities. In certain situations, distally pedicled flaps are a quick and safe alternative to free microvascular tissue transplantation or distant pedicled flaps. However, an exact indication for this method as well as exact planning and performance of the operation is necessary for success. A synopsis of clinical applications of distally pedicled flaps is given. PMID- 1458993 TI - [Intraosseous ganglion in the area of the wrist]. AB - In the differential diagnosis of cystic lesions in bones, the intraosseous ganglion must be included. These tumor-like lesion is rare in the carpus, but often the cause of therapy-resistant pain. Four patients with intraosseous ganglion in the carpus are presented. This bone disease is treated by curettage and bone grafting. Postoperative prognosis is good. PMID- 1458994 TI - [Simplified surgical technique and decreased radiation exposure in dorsal stabilization of spinal fractures]. AB - The dorsal approach for reposition and stabilisation of dorsal and lumbal spine fractures is widely accepted. It is much easier for the surgeon and with lower risk for the patient. For placement of the pedicle screws 3 steps with X-ray fluoroscopy in transversal and anteroposterior direction are necessary: K-wire placement in the pedicle, drill for opening the pedicle and finally screw placement. With the use of two fluoroscopes and a central cannulated drill which is placed over the K-wire the operation gets much shorter, easier and the fluoroscopy time can be reduced significantly. PMID- 1458995 TI - [Total hip joint endoprosthesis in osteopetrosis]. AB - Albers-Schonberg disease (osteopetrosis) is a rare condition, and it very seldom occurs that a patient requiring a hip endoprosthesis is also suffering from this disease. The report describes the difficulties which may confront a surgeon unprepared for such a case and the author illustrates the problem taking the case history of a 46-year-old patient with X-rays and histological tests as an example. The reasons for implantation of either a cemented or cementless endoprosthesis are discussed. PMID- 1458997 TI - [Compartment resection as therapy of choice in subfascial soft tissue sarcoma exemplified by the thigh]. PMID- 1458996 TI - [Carcinoma metastasis in cutaneous osseous metaplasia. Differential diagnosis of osseous tumor metaplasia]. AB - The formation of metastases in heterotopic ossifications is a very rare finding. The example of a 63-year old male who underwent Billroth II procedure because of recurrent duodenal ulcers 30 years ago and median laparotomy of the upper abdomen because of blunt abdominal trauma 9 years ago shows the formation of metastasis of a carcinoma found in the gastroenteral anastomosis in a focus of heterotopic ossification, which was located in the scar of the upper abdominal laparotomy. PMID- 1458998 TI - Simultaneous analysis of immunophenotype and apoptosis of murine thymocytes by single laser flow cytometry. AB - The study of the role of apoptosis in thymocyte development has been hampered by the lack of a means of directly immunophenotyping cells undergoing the early phase of apoptosis. This restriction has been overcome by single laser flow cytometry in which apoptosis is detected by Ethidium Bromide (EBr) staining and cell phenotype by binding of FITC-labelled antibody. The initial phase of apoptosis is observed as a cell population that stains faintly with EBr preceding the characteristically bright EBr-staining normally associated with cell death. Here we directly demonstrate using single laser flow cytometry that CD4+ CD8+ CD3low/CD3intermediate thymocytes undergo apoptosis in vitro in response to glucocorticoid treatment. PMID- 1458999 TI - Noise, sensitivity, and resolution of flow cytometers. AB - The sensitivity and resolution of flow cytometers are functions of the signal produced by a given particle as well as by the noise in the presence of which the signal is detected. The noise is primarily due to the fact that emission of light as well as its detection by photoelectric devises are stochastic processes. This fact leads to equations describing how resolution and sensitivity are limited by the magnitude of the signal, the background, and the photoelectron quantum yield of the detector. The equations are pointing to a method by which the signal and noise of a flow cytometer can be measured in absolute terms, as well as a way to determine fluorescence sensitivity without having to extrapolate to the noise level. The equations appear to be validated when applied to measuring data obtained with two different flow cytometers. PMID- 1459000 TI - Quantification of inter- and intra-nuclear variation of fluorescence in situ hybridization signals. AB - This study aims at the quantification of specific DNA sequences by using fluorescence in situ hybridization (ISH) and digital imaging microscopy. The cytochemical and cytometric aspects of a quantitative ISH procedure were investigated, using human peripheral blood lymphocyte interphase nuclei and probes detecting high copy number target sequences as a model system. These chromosome-specific probes were labeled with biotin, digoxigenin, or fluorescein. Quantification of the fluorescence ISH signals was performed using an epifluorescence microscope equipped with a multi-wavelength illuminator, and a cooled charge coupled device (CCD) camera. Specific image analysis programs were developed for the segmentation and analysis of the images provided by ISH. The fluorescence intensity distributions of the ISH spots showed large internuclear variation (CVs up to 65%) for the probes used. The variation in intensity was found to be independent of the probe, the type of labeling, and the type of immunocytochemical detection used. Variation in intensity was not caused primarily by the immunocytochemical detection method, since directly fluorescein labeled probes showed similar internuclear variation. Furthermore, it was found that different white blood cell types, which harbor different degrees of compactness of the nuclear chromatin, showed the same variation. The intra nuclear variation in intensity of the ISH spots on the two chromosome homologs within one nucleus was significantly smaller (approximately 20%) than the inter nuclear variation, probably due to more constant local hybridization conditions. Due to the relatively small intranuclear variation, copy number polymorphisms of the satellite DNA sequence on chromosome 1 could readily be quantified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459001 TI - Fluorescence ratio measurements of double-labeled probes for multiple in situ hybridization by digital imaging microscopy. AB - To expand the multiplicity of the in situ hybridization (ISH) procedure, which is presently limited by the number of fluorochromes spectrally separable in the microscope, a digital fluorescence ratio method is proposed. For this purpose, chromosome-specific repetitive probes were double-labeled with two haptens and hybridized to interphase nuclei of human peripheral blood lymphocytes. The haptens were immunocytochemically detected with specific antibodies conjugated with the fluorochromes FITC or TRITC. The FITC and TRITC fluorescence intensities of spots obtained with different double-haptenized probes were measured, and the fluorescence ratio was calculated for each ISH spot. Combinations of different haptens, such as biotin, digoxigenin, fluorescein, sulfonate, acetyl amino fluorene (AAF), and mercury (Hg) were used. The fluorescence intensity ratio (FITC/TRITC) of the ISH spots was fairly constant for all combinations used, with coefficients of variation between 10 and 30%. To study the feasibility of a probe identification procedure on the basis of probe hapten ratios, one probe was double-labeled with different ratios, by varying the relative concentrations of the modified nucleotides (biotin-11-dUTP and digoxigenin-11-dUTP) in the nick translation reaction. Measurement of the FITC and TRITC intensities of the ISH spots showed that the concentration of modified nucleotides used in the labeling procedures was reflected in the mean fluorescence intensity of the ISH spots. Furthermore, the ratio distributions showed little overlap due to the relatively small coefficients of variation. The results indicate that a multiple ISH procedure based on fluorescence ratio imaging of double-labeled probes is feasible. PMID- 1459002 TI - Quantification of fluorescence in situ hybridization signals by image cytometry. AB - In this study we aimed at the development of a cytometric system for quantification of specific DNA sequences using fluorescence in situ hybridization (ISH) and digital imaging microscopy. The cytochemical and cytometric aspects of a quantitative ISH procedure were investigated, using human peripheral blood lymphocyte interphase nuclei and probes detecting high copy number target sequences as a model system. These chromosome-specific probes were labeled with biotin, digoxigenin, or fluorescein. The instrumentation requirements are evaluated. Quantification of the fluorescence ISH signals was performed using an epi-fluorescence microscope with a multi-wavelength illuminator, equipped with a cooled charge couple device (CCD) camera. The performance of the system was evaluated using fluorescing beads and a homogeneously fluorescing specimen. Specific image analysis programs were developed for the automated segmentation and analysis of the images provided by ISH. Non-uniform background fluorescence of the nuclei introduces problems in the image analysis segmentation procedures. Different procedures were tested. Up to 95% of the hybridization signals could be correctly segmented using digital filtering techniques (min-max filter) to estimate local background intensities. The choice of the objective lens used for the collection of images was found to be extremely important. High magnification objectives with high numerical aperture, which are frequently used for visualization of fluorescence, are not optimal, since they do not have a sufficient depth of field. The system described was used for quantification of ISH signals and allowed accurate measurement of fluorescence spot intensities, as well as of fluorescence ratios obtained with double-labeled probes. PMID- 1459003 TI - Comparison of BrdUrd and [3H]TdR incorporation to estimate cell proliferation, cell loss, and potential doubling time in tumor xenografts. AB - In this study, two different methods of estimating cell proliferation were compared: cell loss and potential growth rate of xenografted head and neck cancer grown in nude mice based on the detection of DNA incorporation of bromodeoxyuridine (BrdUrd) in one method, and [3H]thymidine ([3H]TdR) in the other. The 21-d-old xenografts were labelled in vivo, either with BrdUrd or [3H]TdR and excised at intervals during 65.5 h. In tumors containing BrdUrd, the percent labelling was measured in mid-S and mid-G1 phase windows of cytograms from bivariate DNA flow cytometry (FCM). In [3H]TdR-labelled tumors, the percent labelled mitoses (PLM) was determined by light microscopy evaluation of autoradiographs. With a computer program based on a theoretical model, the percent labelling versus time after injection was used to analyze cell cycle time, cell loss, tumor growth fraction, and potential doubling time. The values calculated from DNA incorporation with BrdUrd agreed well with those obtained from labelling with [3H]TdR, i.e., cell cycle time 2.3 vs. 2.4 d, and growth fraction 67 vs. 70%. The estimated potential doubling time was 3.1 d and cell loss factor 40% by both methods. Flow cytometry analysis of BrdUrd-labelling is considerably faster than the evaluation of [3H]TdR-labelling, and the present results provide further support for the BrdUrd labelling method as a promising alternative to the PLM method in cell cycle studies designed to evaluate the relevance of cell proliferative properties in relation to biological behavior in xenografted head and neck cancer. PMID- 1459004 TI - Intercalation of anthracyclines into living cell DNA analyzed by flow cytometry. AB - Anthracyclines (ANT) are used in the treatment of leukemia and other cancers. These drugs have been shown to intercalate between the strands of DNA. In the present study, we show that the amount of ANT intercalated into DNA can be determined by measuring the fluorescence resonance energy transfer (FRET) between Hoechst 33342 (H33342) and ANT bound to DNA. The transfer efficiency was found to depend on the amount of disposable ANT but was independent of the amount of H33342 bound to DNA over a wide range of H33342 concentrations. The method was adapted for flow cytometric measurement of FRET in whole living cells and was used to evaluate the degree of intercalation of daunorubicin (DAU) and idarubicine (IDA) into DAU-sensitive and DAU-resistant leukemic cell lines. ANT intercalation into DNA was affected by factors which modify the intracytoplasmic concentration of ANT, and it was shown that the action of ANT and the resistance to ANT could not be attributed solely to the intercalative effect of the drugs. The method has advantages over previously described methods and represents a useful complementary tool in studies on the mode of action of ANT and the mechanisms of chemoresistance. PMID- 1459005 TI - DNA quantification of squamous cell carcinoma of the oesophagus by flow cytometry and cytophotometric image analysis using formalin fixed paraffin embedded tissue. AB - This is the first comparative study of DNA quantification of oesophageal squamous cell carcinoma by flow cytometry (FCM) and image cytometry (ICM) using formalin fixed paraffin embedded tissue. The potential advantages of ICM include the identification of a reliable control cell population; avoidance of non-tumour stromal and inflammatory cell nuclei, nuclear fragments, degenerate cell nuclei and doublets, triplets etc., which are not possible with FCM using archival tissue. Twenty-eight cases, all of the same stage (stage 2a) and similar grade (well or moderately differentiated) were analysed. The cases were separated into two groups, those that had succumbed to tumour in less than 18 months (group A) and those that were tumour free at least 18 months post-resection (group B). Using ICM all 28 tumours yielded interpretable histograms by comparison to 25 of 28 using FCM. Aneuploidy was identified in 100% of cases in group A using ICM (in comparison to 73% by FCM) and in 73% of group B using ICM (in comparison to 44% by FCM). Any tumour aneuploid by FCM was also aneuploid by ICM. Nine cases aneuploid by ICM were euploid by FCM. The mean 5C exceeding rate (% of cells whose nuclei contain a DNA mass equivalent to > 5 sets of 23 chromosomes) was 21% in group A and 14% in group B (P < 0.01). Euploidy was confined to tumours of those patients disease free for more than 18 months. The conclusions of this study are that: firstly, ICM is superior in its yield of interpretable histograms to FCM using formalin fixed paraffin embedded tissue; secondly, ICM is more sensitive in the identification of aneuploid stemlines than FCM; and thirdly, euploid tumours (as detected by ICM) appear to have a better prognosis than aneuploid tumours of similar stage and grade. PMID- 1459006 TI - Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease. AB - The aim of this study was to investigate to which extent acute leukemias could be monitored for residual disease by using atypical antigen combinations as leukemia related markers. Atypical antigenic features were determined by double color flow cytometry and included coexpression of lymphoid and myeloid related antigens, unphysiological coexpression of immature and mature antigens, and lack of an antigen that is normally expressed during maturation. Atypical immunophenotypes were detected in 35 of 68 patients with AML (51.5%) and 15 of 24 patients with ALL (62.5%). When 12 patients with leukemia-associated markers were again analyzed at relapse, the relevant antigen combinations were retained in 11 of them. The sensitivity of this two color flow cytometric assay as determined in dilution experiments was 1 in 10(3) to 10(4) cells. Follow-up studies of bone marrow samples revealed that, after induction chemotherapy cells with leukemia associated markers were detectable in several patients at a frequency of 0.5 to 4%, but only patients in whom the cells with atypical antigens never disappeared suffered from relapse. In contrast, patients who became negative for the atypical cells remained in complete remission (median remission duration after the first negative bone marrow assessment by flow cytometry 52 weeks, range 20-102). We conclude that atypical antigen combinations, which are present in a meaningful number of acute leukemias, are a valuable means of monitoring acute leukemia patients during follow-up. This flow cytometric approach can complement other strategies to get a more accurate definition of remission in acute leukemia. PMID- 1459007 TI - [Inhibiting effect of marine polysaccharides on the development of virus-induced Rauscher leukemia]. PMID- 1459008 TI - [Functional role of cysteine residues of muscle succinyl-C oA-synthetase]. PMID- 1459009 TI - [Identification of new protein kinase genes, similar to kinases of the cdc2 family and expressed in murine hematopoietic stem cells]. PMID- 1459010 TI - [Effect of HIV-1 nef gene on the relationship of cells in bone marrow and peripheral blood in transgenic mice]. PMID- 1459011 TI - [The effect of tobacco smoke on the phospholipid composition and energetics of liver mitochondria]. PMID- 1459012 TI - [Bone marrow high molecular weight glycoprotein, intensifying the activity of granulocyte-macrophage colony-stimulating factor]. PMID- 1459013 TI - [Laparoscopic cholecystectomy: ERCP as standard preoperative diagnostic technique]. AB - In a prospective study 250 patients with proven cholelithiasis and clinical, biochemical and ultrasound indications for laparoscopic cholecystectomy (LC) underwent endoscopic retrograde cholangiography (ERCP) and (if bile-duct stones had been shown) endoscopic papillotomy (EPT). The biliary system was demonstrated in 229 patients (91.6%). Biliary tract stones were confirmed in 18 of 68 patients in whom they had been suspected clinically. In addition, ERCP revealed small stones in the bile-duct in eight of 154 patients with normal biochemical results and unremarkable ultrasound imaging, and in seven patients bile-duct anomalies which required EPT or open cholecystectomy. However, in retrospect five of the patients with cystic duct anomalies could have been treated by LC. The complication rate of ERCP/EPT was 3.2%. It is concluded from these results that, in view of the cost and potential risk to the patient, ERCP before LC can be limited to patients suspected of having bile-duct stones, even though small stones may be missed. PMID- 1459014 TI - [Diabetic gastroparesis and gallbladder disease. Ultrasound diagnosis after multiple-component meals]. AB - Thirty insulin-dependent diabetics (16 women, 14 men, mean age 37.7 [17-74] years) and 12 controls (eight women and four men; aged 20-58 years) were studied by real-time ultrasound before and after each of three meals to assess gastric and gallbladder motility. The diabetics were grouped according to the results into those without (n = 17) and those with diabetic autonomic neuropathy (n = 13). Antral cross-section provided the criterion for gastric emptying. It decreased significantly more slowly in diabetics with autonomic neuropathy than in the other two groups. The difference during the postprandial observation period of 240 min became the greater the longer the interval after the test meal (multivariance analysis: P < 0.001). Gallbladder emptying, too, was slowest in diabetics with autonomic neuropathy (P < 0.05). These results indicate that abnormalities of gastric and gallbladder emptying in diabetics can be recognized by measuring antral cross-section and longitudinal gallbladder area on fasting and 180 min after a test meal. PMID- 1459015 TI - [Patent foramen ovale and platypnea after pneumonectomy]. AB - Six months after a pneumonectomy for myeloma, which had preoperatively been indistinguishable from bronchial carcinoma, a 50-year-old man presented with shortage of breath, cyanosis and episodes of syncope on standing or walking, symptoms which improved on lying down (platypnea). On one occasion these symptoms necessitated controlled artificial ventilation, but even at an inspiratory oxygen saturation of 100%, blood gases only partially improved (pCO2 27 mm Hg, pO2 67 mm Hg, O2 saturation 93%). Right heart catheterization in recumbency revealed a right to left shunt at atrial level of 37% of systemic flow. Contrast medium injection into the inferior vena cava near the heart demonstrated cardiac displacement and rotation. Part of the inferior vena cava flow passed into the left atrium via a patent foramen ovale: it is likely that this shunt increased in the upright position. After surgical closure of the patent foramen ovale and partial relocation of the heart (with a vicryl net) the patient has now remained free of symptoms for 5 years. PMID- 1459016 TI - [Diagnosis of pulmonary tuberculosis]. PMID- 1459017 TI - [Therapy of pulmonary tuberculosis]. PMID- 1459018 TI - [Laser-Doppler technique in diseases of peripheral blood vessels]. PMID- 1459019 TI - [HELLP syndrome]. PMID- 1459020 TI - [Preventive tetanus immunization and avoidance of side effects of booster immunization]. AB - Prevalence of antibodies against tetanus toxoid (tetanus antitoxin titre) was measured in 5,235 males aged 17-60 years, 3,069 (59%) aged 20-22 years. Taking as criterion a threshold value of 0.1 IU/ml, 5,071 (97%) had adequate tetanus immunity. 1,301 of 4,355 aged 21-30 years (30%) actually had antibody concentrations above 6.3 IU/ml. Booster injections are especially contraindicated in this latter group because of the danger of side effects with further toxoid doses. Thoughtless routine booster immunization should therefore be avoided. PMID- 1459021 TI - [Incidence, frequency and resistance characteristics of methicillin-oxacillin resistant Staphylococcus aureus strains in Germany]. AB - In a multicentre study, the methicillin-resistant Staphylococcus aureus (MRSA) isolates in 19 large clinics in Germany were recorded, and the resistance characteristics of these strains were studied. Oxacillin-mannitol-salt agar plates were distributed to all participants to ensure uniformity of screening, and each laboratory used these plates to investigate 200 consecutive Staphylococcus aureus isolates for oxacillin-methicillin resistance. Of the 3,794 evaluable Staphylococcus aureus isolates, 71.5% were penicillin and 3.7% (142) oxacillin resistant; four study centres reported methicillin-oxacillin resistance rates of more than 5%. Of the MRSA isolates, 75% were also resistant to ciprofloxacin, 61% to fosfomycin, 52% to imipenem, 50% to trimethoprim/sulfamethoxazole and 36% to clindamycin. All isolates were sensitive to vancomycin and teicoplanin. Of the Staphylococcus aureus strains isolated from patients in intensive therapy units, 10.4% were methicillin-oxacillin resistant. Drains and catheter tips (9.8% and 5.2% respectively) were the materials with the highest proportions of MRSA. Of the MRSA isolates in this study, 58.2% belonged to lysis group II. PMID- 1459022 TI - [Bronchobiliary fistula in carcinoma of the hepatic duct bifurcation]. AB - Carcinoma of the hepatic duct bifurcation was diagnosed in a 67-year-old women with obstructive jaundice. As metastatic spread could not be demonstrated the carcinoma was removed with a view of achieving a cure (hemihepatectomy, resection of the hepatic duct and the bifurcation, cholecystectomy and hepatojejunostomy). Histological examination indicated adenocarcinoma of the biliary tract. Seven months postoperatively the patient was found to be cachectic and cough up greenish liquid sputum. Bilirubin concentration in sputum was 500 mumol/l. There was no jaundice and total bilirubin concentration was 33 mumol/l. Alkaline phosphatase was 508 U/l, but GOT and GPT were normal (23 U/l and 21 U/l). Computed tomography confirmed the clinical diagnosis of a biliobronchial fistula. The patient died 9 days after renewed hospitalization of tumour cachexia. The biliobronchial fistula was found at necropsy. PMID- 1459024 TI - [Diagnosis of hyperprolactinemia]. PMID- 1459023 TI - [Intracerebral gliofibroma]. AB - A 14-month-old girl had three epileptiform attacks in the course of 6 months, each consisting of rhythmic movements of the right arm and right hand of 5 minutes' duration, followed by a 15-minute period of weakness. There were otherwise no abnormal neurological signs. Prenatal and perinatal development had been uneventful and the mother was healthy. Computed tomography showed a tumour in the left frontoparietal region. Surgery revealed an intracerebral tumour 7 cm in diameter with two large cysts; it was not sharply demarcated from the brain parenchyma, had no connection with the dura and was not infiltrating the ventricular system. The tumour was completely removed and at follow-up 18 months later there was no evidence of recurrence. Histological and immunohistochemical investigations showed that the tumour consisted of closely interwoven astrocytes and fibroblasts, two different cell types the latter of which does not normally occur in the brain. Exact immunohistochemical analysis of the components of a tumour is important because, unlike pure glial tumours, gliofibromas have a good prognosis after complete resections. PMID- 1459025 TI - [Sleep apnea syndrome]. PMID- 1459026 TI - [Nucleoli in nerve cells and tumor genesis]. PMID- 1459027 TI - [Percutaneous endoscopic gastrostomy with 9- or 15-F tubes]. PMID- 1459028 TI - [GnRH agonists in acute intermittent porphyria]. PMID- 1459029 TI - [Pathogenesis of gastroduodenal ulcer]. PMID- 1459030 TI - [The helminth fauna of the red fox (Vulpes vulpes LINNE, 1758) in Nordhessen and Ostwestfalen. 2. Nematodes]. AB - Between November 1989 and June 1990 a total number of 397 foxes were examined for the presence of nematodes in the stomach and the small intestine and 403 foxes for the presence of Trichinella spiralis larvae. The animals came from the districts of Kassel, Arnsberg and Detmold. In 32.7% of the foxes infections with Toxocara canis were found, in 11.1% Toxascaris leonina, in 3.8% Ancylostoma caninum, in 3.5% Uncinaria stenocephala and in 2.3% Capillaria species. In most cases the number of nematodes per fox was low. Only Toxascaris leonina was frequently found with more than 20 specimen per animal. Trichinella spiralis larvae were not found in any of the foxes. PMID- 1459031 TI - Comparative studies on hydatidosis in farm animals in Egypt. AB - A survey on the frequency of hydatid disease in animals slaughtered in Cairo abattoir revealed that the percentage in camels, sheep, pigs, cows and buffaloes attained 31.0%, 1.33%, 4.62%, 0.0% and 0.0% respectively. In camels and pigs the lungs were the main predilection sites of hydatid cysts, while in sheep the liver was the most infested organ. The wall thickness of the cysts was different according to the host species and the location of the cyst. The parasitic membrane of the cysts collected from camels consisted of two layers, an outer layer rich with mucopolysaccharides, and an inner germinal layer; some of its cells were rich with glycogen others were charged with lipids; the latter were mainly concentrated at the origin of the brood capsule. Hydatid cysts from camels showed a large number of calcareous bodies which stained deeply with both von Kossa stain and alcian blue stain. The majority of the examined cysts from sheep showed non-fertile germinal membranes. The most characteristic feature observed in the cysts collected from pigs was the presence of large amounts of fat droplets. PMID- 1459032 TI - [Comparison of IgG determination in foals using commercially available rapid tests]. AB - The three tests (EQUI Z-Test, AGLUTINADE FOAL IMMUNITY, CITE Foal IgG-Test) were evaluated for their accuracy and usefulness in the field. Single radial immunodiffusion was used as reference method. All tests were easily and rapid to perform and results were obtained within a few minutes. It was easy to get the results of the CITE Foal IgG-Test, but use of the EQUI Z-Test and the FOAL AGLUTINADE IMMUNITY-Test needed some practice to get correct results. Results obtained by the CITE Foal IgG-Test correlated to single radial immunodiffusion in 94%, those obtained by FOAL AGLUTINADE IMMUNITY-Test in 74.1% and those obtained by EQUI Z-Test in 57.1%. Best results with a correspondence of 97.1% (CITE Foal IgG-Test) and 100% (EQUI Z-Test) were seen in the group having > 800 mg IgG/100 ml and in the group having < 200 mg IgG/100 ml with 93.3% (CITE Foal IgG-Test) and 82.1% (EQUI Z-Test). The AGLUTINADE FOAL IMMUNITY-Test had the same accuracy in all groups (70.9%-77.8%). PMID- 1459034 TI - [The relationships between the internal and external pelvic measurements of Schwartzbunt cows]. AB - 1118 Friesian cows and 101 Friesian heifers were investigated in internal pelvic measurements and their relationships to external measurements. The mean of the pelvic vertical and the medium diagonally diameter of the pelvis are 19.8 cm and 18.3 cm. 363.9 square centimetres and 76.3 centimetres were found for the pelvic surface and pelvic circumference. The difference between the biggest and smallest pelvis was 295.0 square centimetres. Medium to high coefficiences of correlation were detected between the internal pelvic measurements but relationships between internal and external pelvic measurements were low. From determined external pelvic measurements only the hip breadth provides usefull informations of the pelvic shape. PMID- 1459033 TI - [Sonography during the pregnancy of sheep. I. Fetometry for the determination of the stage of gestation and prediction of the time of parturition]. AB - Transrectal and transcutaneous ultrasonography was performed on 187 pregnant Merino ewes to measure the growth of fetal parameters (fetometry) such as the diameters of the eye, braincase and trunk, the width of one rib with its intercostal space and the crown-rump-length (CRL). In the ewes, cross and longitudinal diameters of the intrauterine lumen around the embryo and fetus were determined. Trunk diameter and crown-rump-length of embryos and fetuses were sonographically determined from Day 26 and size of eyes, braincase and ribs were measured from Day 52 to 66 of gestation. Embryonic resp. fetal parameters and uterine diameters showed almost linear growth rate. Relationship between the measured parameters and days of pregnancy is described by regressions and correlation coefficients. Correlation coefficient between gestational stage and the diameter of the trunk was very narrow (r = 0.98) and between gestational stage and the crown-rump-length resp. eye diameter equalled 89% (r = 0.89). These fetal parameters are appropriate to assess gestational age and growth of ovine fetuses. It can be concluded that sonographic fetometry in the ovine can be valuable for the evaluation of fetal development, the estimation of gestational age and the prediction of parturition dates. PMID- 1459035 TI - [Birth weight and measurements of various body parts of stillborn calves of a large dairy cattle herd]. AB - Stillborn calves (80 animals) originating from one dairy herd were used for studies on allometric measures in newborn calves. In the first approach some factors were neglected and only the effect of the calves' sex was considered. Differences in mean birthweight between male and female calves were reflected in organ and other body constituent weights too, but with different relations between them. Enlarged thyroid glands could be observed in both sexes but more often in female calves meaning that there is no correlation between thyroid size and body weight. Strong correlations of bones, muscles and outer body measures and looser ones of internal organs (thymus, liver, lung, kidneys, spleen) and endocrine glands (adrenal glands) with body weight were found especially in male calves. In some calves the sometimes enlarged liver looked like a fatty liver with its pale yellowish appearance and crumbly consistency. PMID- 1459036 TI - [Campylobacter as the cause of diarrhea in calves]. AB - The modified Preston medium allows the isolation of C. jejuni, C. coli and C. fetus subsp. fetus from intestinal samples of calves at an incubation temperature of 37 degrees C. In the first series of investigation, Campylobacter excretion in calves (n = 7) was followed up to the age of 4 months. In the first 4 days of life, these bacteria could not be detected in any of the animals. Thereafter first C. coli we found in all calves. In 4 animals, only strains of this species were isolated during the whole investigation period. In 3 animals C. fetus subsp. fetus could be detected repeatedly, however C. coli and sometimes C. jejuni were found, too. In the second series of investigation, isolation of Campylobacter from different parts of the gastrointestinal tract or organs was successful in 19 out of 25 diarrhoeal, moribund calves. 16 out of 19 positive animals harboured large amounts of these gramnegative bacteria in the distal jejunum and ileum. In 10 animals out of these 16, the germ colonized also the proximal jejunum and abomasum. From 6 calves, C. fetus subsp. fetus was isolated, and C. jejuni from 7 calves. C. coli was relatively rare. From the lymph nodes of the proximal and distal jejunum, Campylobacter (exclusively C. jejuni) were isolated from 5 animals. Due to the Campylobacter presence in the small intestine of diarrhoeal calves, a contribution of this bacteria within the pathogenesis of calf diarrhoea is possible. Final evaluation of their pathogenesis importance is only positive by means of virulence tests. PMID- 1459037 TI - [Skeletal muscle samples from slaughtered bodies of swine in student laboratories for the study of muscle physiology]. AB - Viable, excitable and contractile samples from gracilis muscle of pig carcasses were used in our student laboratory of muscle physiology. Samples were taken about 20 minutes after stunning. Sampling, transport of the samples and equipment are described. Some examples of registered isometric contractions are shown. PMID- 1459038 TI - Monensin poisoning in dromedary camels. AB - Four female fistulated camels (Camelus dromedarius), 4-5 years of age, were each given two grams of 10% monensin intraruminally daily for six days to study the effect of monensin on the rumen fermentation pattern. Signs of toxicity appeared on the sixth day, and included depression, anorexia, muscular weakness, inability to stand, salivation and regurgitation of ruminal contents. On the eighth day, two animals died. The ruminal contents were replaced in the survivors, but they died on the tenth and eleventh day from the start of the experiment. PMID- 1459039 TI - [An unusual tumor of the nictitating membrane gland of dogs-- a case report]. AB - A tumor of the third eyelid gland was diagnosed in a 13 year old female Chihuahua. Histopathology of the excised tissue revealed an apocrine adnexoma with squamous metaplasia. The literature regarding prolapse and tumors of the third eyelid gland was reviewed. No case with similar morphology to this tumor was described to our knowledge. PMID- 1459040 TI - Successful pretreatment/therapy of soman, sarin and VX intoxication. AB - Chemical pretreatment is effective against a 2 LD50 challenge of soman, sarin or VX or a 5 LD50 challenge of tabun. Chemical pretreatment followed by post challenge therapy should be effective against greater levels of agent. Such tests in guinea pigs are reported here; pretreatment regimens (PRGs) consisted of physostigmine (0.15 mg/kg, im) and an adjunct. The adjuncts [mg/kg, im] used were aprophen [8], atropine (AT)[16], azaprophen (AZA)[5], benactyzine [1.25], benztropine (BT) [4], scopolamine [0.08] and trihexyphenidyl [2]. Pretreatment was given 30 min before, and atropine (16 mg/kg, im) and 2-PAM (25 mg/kg, im) therapy (T) at one min after, 5 LD50s of agent. Results indicate that, all of the PRG+T regimens, except BT-not tested with T, prevent lethality by soman; trihexyphenidyl and scopolamine (the only adjuncts used therein) regimens each prevent lethality by sarin and VX. Against soman, all PRG+T regimens (vs PRG only) may shorten the median recovery time to 2 hrs or less. Even without therapy, the PRGs containing AT, AZA or BT prevent lethality by 5 LD50s of soman; however, used alone, only the PRG containing AZA reduces the incidence of convulsions at this level of soman. PMID- 1459041 TI - The effect of pyridostigmine pretreatment on oxime efficacy against intoxication by soman or VX in rats. AB - This study was done to assess the effects of pyridostigmine (PYR) on a) the accumulation of labelled VX and soman within the brain, b) the therapeutic efficacy of atropine and oxime (2-PAM or HI-6) against intoxication by VX and soman and c) oxime-induced reactivation of inhibited acetylcholinesterase (AChE). In all experiments, rats were given PYR (131 micrograms/kg, im; I70 dose for whole blood AChE) or vehicle 30 min prior to nerve agent. In estimating 3H-agent the accumulation in the brain or estimating blood AChE activity, sufficient soman (47 micrograms/kg, iv) or VX (21.3 micrograms/kg, iv) was given to inhibit 50% of brain AChE activity. In assessing therapeutic efficacy and oxime-induced reactivation of blood AChE, rats were pretreated with PYR, challenged with agent and treated with atropine (16 mg/kg, im) and HI-6 or 2-PAM (100 umoles/kg, im) 30 sec post agent. Whole blood was collected by tail bleeding to monitor peripheral AChE activity at various time points before and after PYR and challenge. Pyridostigmine failed to alter covalent binding of labelled VX or soman in the brain. The 24-hr survival data showed that PYR reduced the therapeutic benefit of atropine and oxime against VX intoxication (but not soman). Protective ratios in VX-challenged rats given vehicle or PYR and treated with atropine + 2-PAM decreased slightly from 2.5 to 2.1 (p > .05), whereas with atropine + HI-6 they decreased significantly from 3.8 to 2.4. Also, AChE reactivation by HI-6 in VX challenged rats was greater (p < .05) in vehicle- than in PYR-pretreated rats. HI 6 significantly reactivated AChE activity in both pretreatment groups (PYR or vehicle) given soman. The data suggest that PYR decreases the overall recovery of inhibited AChE in VX-challenged rats given HI-6; under the conditions used, this adverse effect decreases atropine+oxime efficacy against VX-induced lethality. PMID- 1459042 TI - The effect of tetrabutylammonium ion on chicken brain acetylcholinesterase activity in vitro. AB - The effect of tetrabutylammonium ion on chicken brain acetylcholinesterase activity was investigated. Tetrabutylammonium ion (1-4mM) reversibly inhibited acetylcholinesterase activity of chicken brain (34-73%) in a concentration dependent manner, the IC50 being about 1.1mM. A Lineweaver-Burk plot, as well as a Dixon plot, indicated that the nature of inhibition is noncompetitive with a Km value of 0.134mM and a Ki value of 1.58mM at 37 degrees C. An Arrhenius plot showed that the transition temperature is significantly reduced in the presence of tetrabutylammonium ion. PMID- 1459043 TI - Relationship between activities of cytochrome P-450 monooxygenases in human placental microsomes and binding of benzo(a)pyrene metabolites to calf thymus DNA. AB - Benzo(a)pyrene metabolism in human placental microsomes from smokers was studied. Benzo(a)pyrene metabolites were separated using high pressure liquid chromatographic technique. Reaction of benzo(a)pyrene with a microsomal fraction of placenta from individuals who smoke cigarettes during pregnancy yields 7,8 dihydroxy benzo(a)pyrene as a major metabolite, while 3'-hydroxy benzo(a)pyrene, 4,5 dihydroxy benzo(a)pyrene and quinones constitute minor metabolites. The activities of arylhydrocarbon hydroxylase and 7-ethoxycoumarin deethylase exhibited much higher activities in smokers than in nonsmokers. Examination of specific binding of monoclonal antibodies to cytochrome P-450 isozymes in placental microsomes revealed that cigarette smoking specifically enhanced the level of cytochrome P-450 c and d isozymes in human placental microsomes. Coincubation of 3H-benzo(a)pyrene and calf thymus DNA with placental microsomes yielded acid insoluble 3H-B(a)P from smokers, suggesting that cigarette smoking may induce placental enzymes which convert benzo(a)pyrene into ultimate metabolites to form carcinogen-DNA adducts. PMID- 1459044 TI - Evaluation of acetaminophen-induced developmental toxicity using FETAX. AB - Potential mechanisms of acetaminophen-induced developmental toxicity were evaluated using FETAX (Frog Embryo Teratogenesis Assay-Xenopus). Early Xenopus laevis embryos were exposed to acetaminophen for 96-h in two definitive concentrations-response assays with and without an exogenous metabolic activation system (MAS). Two static renewal tests of acetaminophen and the MAS treated with carbon monoxide, cimetidine, ellipticine, diethyl maleate, and supplemented with glutathione were also performed. Addition of the MAS decreased the 96-h LC50 and EC50 (malformation) values of unactivated acetaminophen 3.9-fold and 7.1-fold, respectively. Addition of the carbon monoxide- and ellipticine-inhibited MAS, as well as the glutathione-supplemented MAS decreased the developmental toxicity of activated acetaminophen to levels near that of the unactivated parent compound. Cimetidine-inhibited MAS also reduced the developmental toxicity of acetaminophen, but not to the extent observed with the carbon monoxide- and ellipticine-inhibited, or glutathione-supplemented MAS. Addition of the diethyl maleate-treated MAS substantially increased the developmental toxicity of acetaminophen. Results indicate that a highly reactive intermediate formed as the result of MFO-mediated metabolism (possibly P-448) significantly increased the developmental toxicity of acetaminophen. Glutathione was also found to play a major role in intermediate detoxification in vitro. PMID- 1459045 TI - Influence of rumen fermentation on response to endophyte-infected tall fescue seed measured by a rat bioassay. AB - Possible alteration of toxicity of endophyte-infected tall fescue by ruminal fermentation was studied using 28 Harlan Sprague-Dawley rats (avg. initial wt., 141 g). These were assigned randomly to one of four treatments in a 2*2 factorial consisting of a 14-day growth period with weights and feed consumption data determined on days 0, 5, 10 and 14. Treatments were: endophyte-infected Kentucky 31 tall fescue seed (E+) or endophyte free Johnstone tall fescue seed (E-) that was incubated for 0 (NON) or 24 hours (INC) with rumen fluid collected from a 290 kg cannulated steer fed a diet containing 37% endophyte-infected tall fescue hay. Diets consisted of 50% lab chow, 39% fescue seed and 11% rumen contents (air-dry basis). Alkaloid content (N-acetyl plus N-formyl loline) for the four diets were 2540, 2680, 0, and 0 micrograms/g for E+NON, E+INC, E-NON, and E-INC diets, respectively. E- treatments gained faster, consumed more feed and converted feed more efficiently (P < .05) than did E+ fed groups. No difference in feed intake was observed within E+ treatments, however, the E+INC diet gained faster (P < .05) and converted feed more efficiently (P < .05) than did E+NON fed rats (2.56 vs 1.96 g/d and 5.94 vs 7.51 g of feed/g of gain for gain and feed conversion, respectively). Including endophyte-infected seed in rat diets depressed performance (ie. intake, gain and feed efficiency). This depression was partially alleviated by a 24-hour incubation with rumen fluid contents suggesting that toxicity of endophyte-infected tall fescue is lessened due to rumen microbial action. PMID- 1459046 TI - Biology of normal luteinizing hormone-releasing hormone neurons during and after their migration from olfactory placode. PMID- 1459047 TI - Clinical counterpoint: gonadotropin-releasing hormone deficiency: perspectives from clinical investigation. AB - Advances in our understanding of the pathophysiology of Kallmann syndrome have come from an interdisciplinary approach involving developmental biology, clinical investigation, and molecular biology. It is equally clear that progress to date is but the first chapter of what will be a fascinating biological story. It now seems likely that the full expression of reproductive potential from the neuroendocrine perspective is likely to be as complicated as other aspects of reproduction, such as the multigene control of external genital differentiation. An analogous story may well emerge for the neuroendocrine control of reproduction in which the GnRH gene is encoded on the eighth chromosome, the protein guiding the embryonic journey of the GnRH-producing neuron to the hypothalamus lies on the X chromosome, and many, as yet to be determined, other genetic loci collaborate in the full expression of reproductive potential. Such a detailed study is warranted not only because of the clinical and genetic implications for an individual patient with this disorder, but also from an organizational theme for the evolution of the species (and its potential regulation). Given the pressing nature of world population growth, obtaining such understanding and its applications to fertility and contraception is crucial. These advances will only come from enlightened interactions of clinical investigators, molecular geneticists, and developmental biologists in which interdisciplinary approaches should be fostered. This should be an exciting story to follow given the remarkable nature of the tools at hand to study these clinical conditions. PMID- 1459049 TI - International glossary of antiepileptic drugs. PMID- 1459048 TI - Clinical counterpoint: vitamin D: new actions, new analogs, new therapeutic potential. PMID- 1459050 TI - Annual meeting of the American Epilepsy Society. Seattle, Washington, December 6 9, 1992. Abstracts. PMID- 1459051 TI - 'For want of a joint the horse was lost...'. PMID- 1459052 TI - How effective is your treatment of bacterial endometritis? PMID- 1459053 TI - Arthroscopic surgery for osteochondritis dissecans of the femoropatellar joint of the horse. AB - Arthroscopic surgery for the treatment of osteochondritis dissecans was undertaken on 252 femoropatellar joints in 161 horses (82 Thoroughbreds, 39 Quarter Horses, 16 Arabians, 9 Warmbloods and 15 others of various breeds). There were 53 females and 108 males. Twenty-two horses were 1 year of age at the time of surgery, 68 were yearlings, 36 were 2-year-olds, 21 were 3-year-olds, and 14 were > or = 4 years old. Ninety-one had bilateral involvement and 70 had unilateral disease. Follow-up information was obtained on 134 horses, including 79 racehorses and 55 non-racehorses: 86 (64%) of these 134 horses returned to their intended use, 9 (7%) were in training, 21 (16%) were unsuccessful and 18 (13%) were unsuccessful due to other defined reasons. Horses with Grade I lesions (< 2 cm in length) had a significantly higher success rate (78%) than did horses with Grade 2 (2-4 cm) or Grade 3 (> 4 cm) lesions (63% and 54% success rates respectively). A significantly higher success rate was also noted for horses operated on as 3-year-olds compared with the remainder of the study population. A significantly lower success rate was noted for yearlings than for the remainder of the population. There was no significant difference in outcome as related to sex of animal involved, racehorse versus non-racehorse, lesion location, unilateral versus bilateral involvement, presence or absence of patellar or trochlear groove lesions, or presence or absence of loose bodies. PMID- 1459054 TI - Fractures of the lateral malleolus of the tibia in 16 horses. AB - Clinical and radiological features of 16 horses with fractures of the lateral malleolus of the tibia are reported. The paper describes surgical techniques used, results obtained and discusses justification for removal. Fourteen fractures were unilateral and two bilateral. There was no left:right disparity. The history included a known traumatic incident in 14 cases. All animals had a tarsocrural joint effusion and 10 had palpable thickening of the lateral collateral ligaments. Crepitus was also palpable in 10 horses. The fracture was identified in all dorsoplantar and 14 of 18 dorsomedial-plantarolateral oblique radiographic projections. Nine fractures were simple and 9 comminuted. All fractures were removed via a tarsocrural arthrotomy. Approaches were dorsolateral in 14 joints, plantarolateral in 3 and dorsolateral and plantarolateral in 1. After an ascending exercise programme horses returned to work 6 months after surgery: 15 horses were free of lameness after 17-62 months, with 13 animals performing at a level similar to pre-injury standard. PMID- 1459055 TI - Septic arthritis in 15 standardbred racehorses after intra-articular injection. AB - Case histories, results of synovial fluid analyses, treatment regimens and outcome are described for 15 adult Standardbred horses with confirmed post injection septic arthritis. Joint sepsis followed injection of corticosteroids, hyaluronic acid, polysulphated glycosaminoglycan, or local anaesthetic. The median interval from injection to appearance of clinical signs was 2.5 days, and median interval from injection to referral was 9 days. The median initial synovial leucocyte count on admission was 57 x 10(9)/litre, but there was a wide range of values (18-258 x 10(9)/litre). The median synovial neutrophil percentage was 95% (77-99%). All bacterial isolates were Gram-positive cocci, 86% of which were staphylococci. All treated horses (12/15) initially received broad-spectrum parenteral antibiotic therapy, and the articulations of all horses except one were lavaged, either with non-surgical through-and-through techniques only (N = 3), or surgically with arthrotomy (N = 1) or arthroscopy (N = 7). The owners of all treated horses were contacted and racing records were consulted. Eleven of 12 horses returned to racing. Outcome was judged as either satisfactory (3/12) if the horse had returned to racing levels similar to or better than before treatment, or unsatisfactory (9/12) if the horse had poorer performance or could not return to racing. The 3 horses with satisfactory follow-up had been treated with arthroscopy and post-surgical closed suction drainage. The results of bacterial cultures suggest that the initial antimicrobial agents used should be effective against penicillin-resistant staphylococci. PMID- 1459056 TI - A retrospective study of 192 horses affected with septic arthritis/tenosynovitis. AB - The medical records of 192 horses with septic arthritis/tenosynovitis 1979-1989 were reviewed. Forty-three horses developed infection after an intra-articular injection, 46 following a penetrating wound, 25 following surgery, 66 were foals less than 6 months old, and 12 were adult horses without a known aetiology. Haematogenous infection of a joint occurs in adult horses and should be considered as a differential diagnosis in horses with an acute onset of severe lameness. The aetiology of the infection had a significant effect on the type of bacteria identified by culture. Staphylococcus was cultured from most of the horses that developed infection following a joint injection or surgery, 69% of the horses from which an organism was identified. Horses that developed infection secondary to a penetrating wound frequently provided cultures of more than one organism; Enterobacteriaceae and anaerobes were more frequently isolated in this group. The most common organisms isolated from foals were Enterobacteriaceae; E. coli was identified in more than 27% of the foals. The hock was the most frequently involved joint. Multiple treatments were used over the 10-year period of study. Survival rates were lowest in foals; only 45% survived to be released from the hospital. Survival was greater in adult horses; 85% of the horses that were treated were released from the hospital. Survival was significantly greater in horses with septic tenosynovitis; all 14 of the horses that were treated survived. Survival was not significantly affected by the joint involved or by the type of bacteria cultured from the synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459057 TI - Open drainage, intra-articular and systemic antibiotics in the treatment of septic arthritis/tenosynovitis in horses. AB - Open drainage was used to treat 26 horses with persistent or severe septic arthritis/tenosynovitis. Infected synovial structures were drained through a small (3 cm) arthrotomy incision that was left open and protected by a sterile bandage. Joint lavage was performed in all 26 horses. In addition to systemic antibiotics, 23 of these horses were also treated with intra-articular antibiotics; amikacin (17 horses), gentamycin (2 horses), cefazolin (2 horses), and 2 horses were injected at different times with gentamycin and amikacin. The infection was eliminated from the involved synovial structures in 25 of 26 horses; 24 survived and were released from the hospital. The arthrotomy incisions healed by granulation in 16 horses; in 9 horses the arthrotomy incision was sutured closed once the infection was eliminated. Seventeen horses returned to soundness and resumed athletic function. Open drainage was an effective method of achieving chronic drainage from a joint or tendon sheath. It is indicated in horses that have established intra-synovial infections or in horses that do not respond to joint lavage through needles. PMID- 1459058 TI - Antimicrobial susceptibility of bacterial isolates from 233 horses with musculoskeletal infection during 1979-1989. AB - Bacterial culture and susceptibility results were analysed from 233 horses with septic arthritis/tenosynovitis or osteomyelitis that developed after fracture repair. Antibiotics were deemed highly effective, effective or ineffective if > or = 85%, 70-84.9% or < 70% of the isolates were susceptible respectively. In total, 424 bacterial types were isolated; 386 were aerobic or facultative and 38 were anaerobic. Enterobacteriaceae (28.8%) were the most common bacterial group isolated, followed by non-beta-haemolytic streptococci (13.0%), coagulase positive staphylococci (11.8%), beta-haemolytic streptococci (9.4%), and coagulase-negative staphylococci (7.3%). The remainder of the organisms were other Gram-negative (15.8%), other Gram-positive (2.3%) and miscellaneous (2.6%) bacteria. Penicillin and ampicillin were highly effective against beta-haemolytic streptococci, but were ineffective against other bacteria. Ampicillin was no more effective than penicillin against most bacteria. Amikacin was the most effective antibiotic against the wide range of bacteria isolated in this study. Amikacin was highly effective against coagulase-positive staphylococci, Enterobacteriaceae and Pseudomonas and was effective against coagulase-negative staphylococci and Actinobacillus. Gentamycin was not highly effective against any bacterial group; but was effective against coagulase-positive and negative staphylococci, Pseudomonas, Salmonella and Actinobacillus. Kanamycin was ineffective against all bacteria with the exception of Actinobacillus. Cephalothin was highly effective against beta-haemolytic streptococci, coagulase-positive staphylococci and Actinobacillus and was effective against coagulase-negative staphylococci.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459059 TI - Evaluation of progesterone treatment to create a model for equine endometritis. AB - To investigate a model for equine endometritis, 12 mares with normal reproductive tracts were divided into 2 groups. All mares received progesterone in oil, 250 mg im, daily. At 5 days after initiation of progesterone administration, the uteri were inoculated with 10(6) colony forming units of Pseudomonas aeruginosa. The day of inoculation was designated Day 0. On Day 6, endometrial swab samples yielded P. aeruginosa in 5 mares; samples from the other 7 mares yielded heavy growth of Escherichia coli, Streptococcus zooepidemicus, Klebsiella pneumoniae, Enterobacter spp., Citrobacter diversus, Staphylococcus epidermidis and Streptococcus morbillorum. On Days 6, 7 and 8, Group A mares received intrauterine infusions of 6 g ticarcillin disodium and 0.2 g clavulanate potassium in 100 ml sterile saline. Group B mares received infusions of saline only. The incidence of swab specimens yielding no bacterial growth was significantly higher in Group A than Group B mares on Days 8 and 13 (4/6 vs 0/6). Swab samples from 5 of the 6 mares in Group A yielded growth of fungi on Days 13 and 19. Mares in Group B were then similarly treated with ticarcillin/clavulanate infusions, on Days 19, 20 and 21. The incidence of swab specimens yielding no bacterial growth was 2/6 and 1/6 on Days 21 and 26, respectively; fungi were not recovered from these mares at any time. The incidence of no-growth swabs after antibiotic treatment tended to be higher in Group A and incidence of fungal recovery after antibiotic treatment was significantly higher in Group A.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459060 TI - Effects of high-intensity exercise on plasma catecholamines in the thoroughbred horse. AB - In Study 1, a single speed test of 6 to 12 m/sec was performed for 2 mins at an incline of 5 degrees on a high-speed treadmill (single-step test). Only one speed was performed per session and blood samples were taken before and after the test. In Study 2 horses cantered for 1 min at increasing speeds of 6 to 13 m/sec on an incline of 3 degrees (multiple-step test). Blood samples were taken before exercise, throughout the test and during recovery. In the single-step test plasma concentrations of adrenaline and noradrenaline both increased at speeds of 9 m/sec, as did blood lactate. Mean concentrations of adrenaline and noradrenaline at the end of the 12 m/sec test were 153 and 148 nmol/litre, respectively. Plasma concentrations were similar over all speeds although there was a tendency for the increase in noradrenaline to be greater than that of adrenaline at the lower speeds. The multiple-step test resulted in smaller increases in both adrenaline and noradrenaline. Although again closely correlated, increases in adrenaline were 20-30% greater than those for noradrenaline. In both exercise models, changes in plasma adrenaline and noradrenaline values with exercise showed an exponential relationship to plasma lactate. A plasma half-life of less than 30 secs was indicated during recovery from the multiple-step test. Changes in adrenaline and noradrenaline were much greater than previously recorded in man and emphasise the importance of catecholamines in mediating the physiological response of the horse to exercise. PMID- 1459061 TI - Outcome of treatment in 23 horses with progressive ethmoidal haematoma. AB - This paper describes the outcome of treatment in 23 horses with an ethmoidal haematoma. In 22 cases a diagnosis could be made by endoscopic means alone but in 1 horse the lesion was confined to the maxillary sinus and a diagnosis was made only at surgery. One horse was destroyed at the owner's request but the other 22 underwent radical excision of the lesion via a facial flap approach under general anaesthesia. Post-operative haemorrhage was controlled by nasal packing with a gauze bandage and this was removed between the 2nd and 4th post-operative day. One horse died from encephalitis the day after surgery. Other complications included facial wound dehiscence, sequestration and suture periostitis. Of 21 horses followed up post-operatively there was definite recurrence of lesion in 2 cases and possibly a third. However, in 18 horses there was no evidence of recurrence (follow up times were 2 to 85 months). It is suggested that radical excision of the lesion provides an effective means of treatment. PMID- 1459062 TI - Effect of dietary biotin supplement on equine hoof horn growth rate and hardness. AB - Over a 10-month period, 24 randomly selected riding horses were fed various amounts of biotin. Statistically significant improvements in growth rates and hardness of hooves were produced by biotin supplementation. Greater growth rates and hardness were achieved at a daily dose of 15 mg than at 7.5 mg. Increased hoof hardness was greatest in the hoof quarters and toe. No ring formation occurred in hooves of horses fed biotin intermittently. PMID- 1459063 TI - Effects of hypoxia and azotaemia on the pharmacokinetics of amikacin in neonatal foals. AB - The effects of hypoxia and azotaemia on the pharmacokinetics of amikacin were evaluated in 20 full-term neonatal critically ill foals which required 24-h supportive care, antibiotics and dextrose-supplemented polyionic fluids given intravenously, nasal insufflation with oxygen and nutritional supplementation. There was no association between sepsis score or survival and pharmacokinetic parameters. Concurrent hypoxia and azotaemia were associated with significantly decreased clearance and increased peak and trough serum concentrations of amikacin; however, peaks or troughs did not exceed toxic values. Derangements in serum peak, trough and clearance values, which were present on admission, persisted over the 6-day duration of this study. Daily monitoring of serum amikacin concentration revealed a tendency to underdose (particularly in foals receiving aggressive fluid therapy), which necessitated increasing the dose/kg body weight (9-12 mg/kg) and increasing the dose interval (10-12 h) in 40% (8/20) of the cases, so that blood concentrations of amikacin could be maintained within the target range of 3-15 micrograms/ml. Amikacin-induced nephrotoxicity was not indicated by conventional laboratory testing, nor was it strongly suspected after examination of post mortem lesions. PMID- 1459064 TI - Catheterisation of carotid artery in horses using ultrasonography. PMID- 1459066 TI - Pharmacokinetics of ceftiofur sodium in neonatal foals after intramuscular injection. PMID- 1459065 TI - Effect of vitamin E status on lipid peroxidation in exercised horses. PMID- 1459067 TI - A field evaluation of three methods of administration of anthelminthics to horses. PMID- 1459068 TI - Pemphigus foliaceus in a 2-month-old foal. PMID- 1459069 TI - Pulmonary plasma cell granuloma (inflammatory pseudotumour) in a horse. PMID- 1459070 TI - Comparison of two surgical methods for treatment of crib-biting in horses. PMID- 1459071 TI - 'Laterally aggregated' polyacrylamide gels for electrophoresis. AB - A new method is described for producing highly porous polyacrylamide matrices: polymerization in presence of a preformed hydrophilic polymer. If a standard mixture of monomers (e.g., 5%T, 4%C) is polymerized in presence of, e.g., polyethylene glycol (PEG) 10 kDa, lateral chain aggregation occurs, with formation of large pore sizes. In PEG 10 kDa, the transition from a small- to a large-pore gel is clearly apparent at 0.5% PEG addition and reaches a plateau already at 2.5% PEG. Even with shorter PEG fragments (6.2 and 1 kDa) this transition occurs, but with progressively larger amounts of PEG in solution (up to 25% for the 1 kDa species). Other polymers such as hydroxymethyl cellulose (1000 kDa) and polyvinyl-pyrrolidone (360 kDa and 25 kDa) are also able to elicit this phenomenon. It appears that lateral chain aggregation (before the cross linking event) is induced via intra-chain hydrogen bonding, since urea and temperature strongly inhibit it, whereas tetramethylurea (an agent quenching hydrophobic interactions) does not hamper it. By scanning electron microscope, it is found that the maximum pore size obtained in a 5%T, 4%C gel in presence of 2.5% PEG 10 kDA is of the order of 0.5 micron, whereas the same 5%T, 4%C control gel would have an average pore diameter of 5 nm. Thus, an increment of pore size of about 2 orders of magnitude is obtained: in these new matrices, a 21000 bp DNA fragment exhibits a much greater migration than in a control gel in which the sample is entrapped at the application site. PMID- 1459073 TI - Information on DNA conformation derived from transverse pore gradient gel electrophoresis in conjunction with an advanced data analysis applied to capillary electrophoresis in polymer media. AB - Abnormally slow migration of DNA is conventionally viewed as being due to an abnormal conformation relative to "linear" standards. The evidence for this rests on a few instances where nonlinear DNA structures have been established by independent methods and yield low mobilities relative to standards. Transverse pore gradient gel electrophoresis of authentically bent kinetoplast DNA and of an upstream activator sequence (UAS) of an E. coli operon promoter shows in addition that curves of migration distance vs. gel concentration ("Ferguson curves") of such abnormally conformed DNA differ from those of "linear" standards. Since Ferguson curves are interpretable with regard to molecular size in concordance with a mathematical model (Ogston model), transverse pore gradient gel electrophoresis provides a simple means of correlating abnormally slow migration of DNA with molecular size. In addition, transverse pore gradient gel electrophoresis is able to distinguish between DNA banding which exhibits a steeper dependence on gel concentration than "linear" standards from one which shows the same dependence. The former appears characteristic of circularly bent DNA and gives rise to a substantial retardation, the latter of bending across a knot or kink in the DNA chain associated with a relatively minor retardation relative to standards. Circularly bent restriction fragments formed from kinetoplast DNA retain the characteristic intersecting Ferguson curves on the transverse pore gradient gel. Another authentically "abnormal" DNA structure recognizable on transverse pore gradient gels is supercoiled DNA derived from the reaction of topoisomerase with a plasmid. Different lengths of supercoiled sequences give rise to parallel Ferguson curves clearly intersecting with those of linear standards.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459072 TI - The effect of gel structure on matrix orientation. AB - Four polymeric gels of different structure, low electroendosmosis (LE) agarose, highest electroendosmosis (HEEO) agarose, beta-carrageenan, and polyacrylamide, were studied by transient electric birefringence to determine the importance of various structural features on the orientation of the gels in an electric field. The two types of agarose, but not the polyacrylamide or beta-carrageenan, exhibited anomalous orientation effects. Both agarose and beta-carrageenan exhibited large birefringence signals, suggesting that the noncovalent hydrogen bonds joining the agarose fibers within the matrix allow the high degree of orientation of the gel. The spatial arrangement of the sugars of the agarose backbone is necessary for the anomalous orientation effects in reversing electric fields. PMID- 1459074 TI - Molecular sieving of lambda phage DNA in polyacrylamide solutions as a function of the molecular weight of the polymer. AB - Electrophoresis of lambda phage DNA was carried out in solutions at various concentrations of uncrosslinked polyacrylamide of 0.6, 1, 5 and 9 x 10(6) molecular weight (Mw) with narrow Mw distribution. By inspection of mobilities in the various concentration ranges, it appears that mobilities decrease, and retardation increases, with increasing Mw. The relation between electrophoretic retardation and the Mw of the polymer was also interpreted (i) in the manner previously applied to nonlinear Ferguson plots and compatible with the Ogston model; and (ii) empirically, on the basis of the first derivatives of the functions describing the Ferguson plots at the polymer concentrations used. Interpretation (i) shows that the retardation increases linearly in the order of 0.6, 1, 5 and 9 x 10(6) Mw of polyacrylamide. Interpretation (ii) shows a nonlinear increase of retardation in the Mw range 5 to 9 x 10(6), and a decrease in retardation as Mw is raised from 0.6 to 5.0 x 10(6). Hypothetically, interpretation (ii) can be explained mechanistically by a progressive change, as the polymer size is increased, from a collision with the surface of the polymer fiber to one occurring after permeation in the interior of a random-coiled fiber. Interpretation (i) may fail to detect that change due to the large difference between DNA mobility in solutions of the smallest polymer and the free mobility. DNA peak detection in all of the four size classes of polyacrylamide in solution is limited to relatively narrow ranges of polymer concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459075 TI - Advances in DNA electrophoresis in polymer solutions. AB - DNA electrophoresis in gels and solutions of agarose and polyacrylamide was objectively evaluated with regard to separation efficiency at optimal polymer concentrations. In application to DNA fragments, polyacrylamide gels were superior for separating fragments of less than 7800 bp, and agarose gels are the best choice for larger fragments. Agarose solutions are nearly as good as polyacrylamide gels for small DNA (< 300 bp). Agarose solutions have a higher efficiency than polyacrylamide solutions for DNA of less than 1200 bp. Separation efficiency sharply decreases with increasing length of DNA. Retardation in polyacrylamide solutions was found to depend on polymer length in a biphasic fashion. The choice of resolving polymer concentrations depends on the progressive stretching of DNA in proportion to polymer concentration. The rate of that stretching appears higher in polyacrylmide solution than in gels or in liquid or gelled agarose. Application of polymer solutions to capillary electrophoresis raises further problems concerning agarose plugs, DNA interactions with the polymers, operation at low field strength and long durations as well as detection sensitivity. PMID- 1459076 TI - High-throughput automated DNA sequencing facility with fluorescent labels at the European Molecular Biology Laboratory. AB - One of the aims of the facility is to develop and push the automated on-line DNA sequencing gel technology to its limit in sequence throughput, which may be somewhere around 100 kilobases of sequence per device per day. Key new developments were initiated and applied in operation on the European Molecular Biology Laboratory (EMBL) automated sequencer and its commercial version A.L.F. (Pharmacia). Sequencing speed was increased by a factor of 10-20, up to 1500 bases per hour per clone on ultrathin (about 100 microns) gels, while the resolution and reading length were extended to 1000 bases on gels with 50 cm separation length, using fluorescein-15-*dATP as the internal label. With our sequencing strategy, closing about 40% of the sequence with "walking" primers and F-15-*dATP as internal label, we sequenced both strands of a cosmid insert of 38.5 kb in length, each strand twice, in only 430 sequencing reactions and with average reading of 380 bases per reaction. PMID- 1459077 TI - Manual sequencing using pulsed field. AB - The use of pulsed fields in manual sequencing opens up the compression zone found with a DC field and extends the range of resolution from a few hundred bases to several thousand bases. The band inversion problem is overcome with the proper pulsing conditions, and the bands are sharper than for the DC field case. Accurate visual reading is possible up to about 800-900 bases. The method is compatible with automation techniques, since the band spectrum is stretched continuously during migration, and the smaller fragments are run off the gel. PMID- 1459078 TI - Towards a fingerprint method covering the immunological genome. PMID- 1459079 TI - Physical genome analysis of bacteria. AB - Pulsed-field gel electrophoresis (PFGE) is a general analytical tool to separate large DNA molecules and may therefore be applied to problems from all areas of bacteriology. The genome size of bacteria covers the range of 0.6 to 10 megabase pairs. For genome fingerprinting, the bacterial chromosome is cleaved with a restriction endonuclease that gives a resolvable and informative number of five to one hundred fragments on the PFGE gel. Restriction enzymes are chosen according to GC content, degree of methylation, and codon usage of the respective bacterial genus. Macrorestriction fingerprinting allows the identification of bacterial strains and the distinction between related and unrelated strains. If fragment patterns of several restriction digestions are quantitatively evaluated, strains can be classified according to genetic relatedness at the level of genus, species, and biovar. In particular, members of a clonal lineage can be uncovered. Hence, any problem from applied, environmental, and clinical microbiology may be addressed by PFGE restriction analysis where the spatiotemporal spread of a bacterial clone is of interest. In bacterial genomics, PFGE is employed for the top-down construction of macrorestriction maps of the chromosome which yields data about genome organization, mobile genetic elements, and the arrangement of gene loci and gene families. The genomic diversity of a bacterial species is elucidated by comparative chromosome mapping. Map positions of restriction sites and gene loci of interest serve as landmarks to assess the extent of gross chromosomal modification, namely insertions, deletions and inversions. Intra- and interspecies comparisons of genome organization provide insights into the structure and diversity of bacterial populations and the phylogeny of bacterial taxa. PMID- 1459080 TI - PCR amplification products are of limited use for the study of DNA/protein interaction. AB - Conventional methods for labeling double-stranded DNA lead to high specific activity. Yet they often alter the target DNA sequence to such an extent as to prevent a meaningful protein/DNA interaction analysis. Therefore we tried to establish a polymerase chain reaction (PCR)-based method which allows radiolabeling to high specific activity and should maintain the protein binding capability of small double stranded DNA fragments. By using PCR it is possible to label double stranded DNA to high specificity, but the protein binding capability of such DNA is drastically reduced. PMID- 1459081 TI - Genetic heterogeneity of prostatic carcinoma-derived cell lines as emphasized by DNA fingerprinting. AB - To investigate genetic heterogeneity during in vitro cultivation of human prostatic carcinomas following radical prostatectomy we performed DNA fingerprinting using the digoxygenin-labeled probes (GACA)4 and (GTG)5. DNA was isolated from fresh material stemming from different areas within one tumor and from cell cultures of the same material. The patterns which were obtained by the nucleolar organizer region (NOR)-specific probe (GACA)4 exhibit only a few prominent low molecular mass bands and no differences were observed between any of the tumors analyzed so far. Changes in the fingerprint pattern occurred between cell cultures derived from different areas within one tumor when the DNA was cleaved by HaeIII and signals detected with the (GTG)5 probe. The "area specific" pattern was stable during several subcultivations of these cell lines, indicating genetic stability of these prostatic carcinoma cells in vitro. Thus individual cell lines derived from radical prostatectomy seem to represent a biological system very close to the situation in vivo. PMID- 1459082 TI - Pulsed-field gel electrophoresis analysis of a Pseudomonas aeruginosa pathovar. AB - This paper presents the genome organization and mobility of Pseudomonas aeruginosa strains that had been isolated in half-year intervals from 30 patients with cystic fibrosis since the onset of colonization over a 2- to 8-year period. The chromosomes were digested with DraI or SpeI, separated by pulsed-field gel electrophoresis, blotted and hybridized with probes encoding housekeeping or virulence genes. Strains were differentiated by relatedness of macrorestriction fingerprints. After some turnover of strains during the first two years of colonization, each patient had acquired a set of strains that diversified during the course of the disease. In the majority of patients, two clonal lineages were found to account for colonization in the air passages but each lung habitat was characterized by some specific signature of bands in the macrorestriction fragment pattern. PMID- 1459083 TI - A PacI/SwaI map of the Pseudomonas aeruginosa PAO chromosome. AB - The PacI/SwaI macrorestriction map of the 5.9 Mb Pseudomonas aeruginosa PAO (DSM 1707) genome was constructed by fragment size comparisons of complete single and double digests and hybridization with probes of known genomic localization. P. aeruginosa PAO contains five recognition sites for PacI and six sites for SwaI. An integrated DpnI/PacI/SpeI/SwaI map was obtained by fragment pattern and Southern blot hybridization analyses of all combinations of double digestions and by two-dimensional pulsed-field gel electrophoresis mapping protocols. PMID- 1459084 TI - Chromosomal localization of the HYP2-gene in Saccharomyces cerevisiae and use of pulsed-field gel electrophoresis for detection of irregular recombination events in gene disruption experiments. AB - In the hypusine-containing protein (HP), a specific lysine residue is modified by spermidine to form the unusual amino acid hypusine (4-amino-2 hydroxybutyllysine). The HP has been designated as an eucaryotic translation initiation factor--eIF-5A--because of its stimulating effect in the methionyl puromycin in vitro assay. Nevertheless, the precise function of this protein remains to be elucidated. In the yeast Saccharomyces cerevisiae two genes, HYP1 and HYP2, coding for two different forms of the HP, are present. The HYP1-gene is identical to the ANB1-gene and has already been localized on chromosome X. However, the chromosomal localization of the HYP2-gene has not been elucidated. By using pulsed-field gel electrophoresis (PFGE) and subsequent Southern blotting, we determined the localization of the HYP2-gene to chromosome V. Furthermore, PFGE was used for the detection of irregular recombination events, such as misintegration or integration into a duplicated gene, and in gene disruption experiments using haploid and diploid yeast cells. The obtained data support the critical role of the HP for cell viability. PMID- 1459085 TI - Evaluation of isoelectric focusing runs as specific resistance/volthour plots. AB - Isoelectric focusing (IEF) runs, e.g. on ultrathin gels, are characterized by an extensive change of gel electric parameters, caused by the rearrangement of carrier ampholyte components from a uniform distribution to a highly ordered pH gradient. A particularly important parameter is the specific resistance rho [Ohm*cm] which has been determined in polymerization mixtures (with and without carrier ampholytes) and in 125 x 0.15 mm ultrathin gels, pH 3-10 with 5% T, 3% C, 5% Servalyt carrier ampholytes, pH 3-10. The starting specific resistance rho of ultra-thin IEF gels, calculated from the geometric gel dimensions and electric current values (V, mA), is in agreement with the data determined directly in 30 mL samples of polymerization mixtures by using a conductivity meter. Electric specific conductivity/Volthour (Vh) plots proved to be a valuable tool for the evaluation of gel systems with and without protein samples during IEP runs. These plots are usually S-shaped, indicating that the key part of pH gradient formation takes places in a relatively short time. A "good" ultrahin gel, after a short lag phase, shows a rapid increase in specific resistance due to a rapid pH gradient formation and a slope of about 18 Ohm*cm/Vh. IEF is finished in about 3000 Vh. After prolonged gel storage, and especially in partially dried gels, the electrical parameters approach equilibrium only slowly, as indicated by the relatively shallow slope (8.9 Ohm*cm/Vh). Accordingly, separations need more than 4000 Vh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459086 TI - Analysis of members of the Ig-gene superfamily by thermal gradient polyacrylamide gel electrophoresis. AB - A solid aluminum block, connected with a warm and cold thermostated waterbath, provided for a linear transversal temperature gradient (TG) during polyacrylamide gel electrophoresis (PAGE). Noncovalently bound heavy chain dimers as well as heavy-light chain dimers, derived from human monoclonal IgG, could be melted into monomers using a 40-75 degrees C TG under conditions of sodium dodecyl sulfate PAGE. Using native PAGE, major histocompatibility complex (MHC) class I molecules, preloaded with the iodinated peptide FAPGNYPAL could be melted in a 4 40 degrees C TG to release the peptide. The method is in general applicable to thermal stability analysis of noncovalently bound hetero-oligomers if the product after melting possess different electrophoretic mobilities. PMID- 1459087 TI - Mass spectrometric analysis of blotted proteins after gel electrophoretic separation by matrix-assisted laser desorption/ionization. AB - The molecular masses of electroblotted proteins were determined with a time-of flight mass spectrometer by matrix-assisted laser desorption/ionization directly from blot membranes. Therefore standard proteins, separated by polyacrylamide gel electrophoresis, were electroblotted onto polyvinylidene difluoride or polyamide membranes by standard procedures. Pieces of membrane containing the protein of interest were soaked in matrix solution and analyzed in the mass spectrometer. PMID- 1459088 TI - Thin-layer electrophoresis with PhastSystem facilitates analysis of phosphoamino acids from proteins bound to Immobilon. AB - A modification of thin-layer electrophoresis of phosphoamino acids on miniplates, using the PhastSystem (Pharmacia) is described. This method not only reduces the amount of radioactivity required but also the radioactive waste. In addition, it also decreases the handling of hazardous substances and takes only a fraction of the time required for the standard procedure. PMID- 1459089 TI - Purification to single isoforms of a secreted epidermal growth factor receptor in a multicompartment electrolyzer with isoelectric membranes. AB - A purified, size-homogeneous (100 kDa), desialylated form of a truncated, soluble form of the epidermal growth factor receptor secreted by A431 human tumor cells has been found, by isoelectric focusing in immobilized pH gradients, to consist of two major isoforms (with pIs of 6.96 and 6.71), one intermediate form (pI 6.45) and a number (> 10) of minor components. The two major components have been purified to charge homogeneity by isoelectric focusing in a multicompartment electrolyzer with buffering isoelectric membranes having the following pI values: 5.90, 6.63, 6.76, 6.92, 7.05 and 7.35. Such single pI species are presently used for attempts at crystal growing. PMID- 1459091 TI - Identification of peaks in capillary zone electrophoresis based on actual mobilities. AB - A procedure is proposed for the calculation of the actual effective mobility of a zone from its migration time. It is based on the use of internal standards with known mobilities; the use of two internal standards provides reliable mobility data even if the magnitudes of the effects of sample composition, capillary temperature, capillary length, migration distance, used voltage, as well as the tube length occupied by the injected sample are unknown. Formulas have been derived for the calculation of the actual mobilities, and their experimental verification has been carried out by using a model set of anionic solutes with mobilities ranging from -56 to -20 x 10(-9) m2V-1s-1 and chloride as the ion modelling the effect of the sample matrix. PMID- 1459090 TI - Preparative continuous separation of biological particles by means of free-flow magnetophoresis in a free-flow electrophoresis chamber. AB - For sorting, cells or cellular components can specifically be labeled by antibody coated magnetic beads. We have developed a device for continuous magnetic sorting based on the flow-chamber of a free-flow electrophoresis system. Magnetically labeled particles are injected into a given continuously flowing chamber buffer and pass an inhomogeneous magnetic field, configurated perpendicular to the flow direction. According to its magnetic moment, the magnetic material is deviated into the direction of the magnetic forces, while nonmagnetic material passes the field without interaction. The magnetic forces can be changed with the electrical current of the solenoids producing the magnetic field. As in the free-flow electrophoresis system, the particle fractions are collected in different vials. On-line control of the experiments can be performed by an optical scanning system. Experiments with model particles achieved a sorting purity of more than 99% at a rate of up to 5 X 10(8) particles per hour. In experiments with blood cells, a high enrichment of either B-or-T-lymphocytes was obtained. In contrast to free-flow electrophoresis, there is no limitation, in principle, regarding the type of chamber buffer to be used. This allows an optimal adaptation of the buffer conditions to the requirements of vital sorting. The preliminary results so far confirm this conclusion. PMID- 1459093 TI - Enantiomers resolution in capillary zone electrophoresis by using cyclodextrins. AB - Cyclodextrins added to the background electrolyte are shown to be useful for the resolution of racemic compounds in their enantiomers. Several parameters have to be controlled in order to achieve resolution, e.g., cyclodextrin type, concentration, analyte shape, as well as column temperature. The resolution of nor-epinephrine, epinephrine and isoproterenol in their enantiomers decreased by increasing the column temperature. Octopamine and ketamine have been resolved by supporting the background electrolyte with 2, 6-di-O-methyl-beta-cyclodextrin. In spite of the stronger inclusion-complex of ketamine than octopamine with the modified cyclodextrin its resolution was not satisfactory. PMID- 1459092 TI - Application of capillary electrophoresis in peptide research. AB - Comparison of high performance liquid chromatograms (HPLC) with capillary electrophoresis shows the latter to be superior in many cases owing to rapid separation, high resolution and high sensitivity. This is demonstrated with two examples (i) the isolation of natural peptides from bovine tissue and (ii) characterization of a synthetic peptide mixture with the natural sequence (fragment) of the human immunodeficiency virus (HIV) transmembrane glycoprotein gp 41 env. PMID- 1459094 TI - Capillary electrophoresis of macromolecules in 'syrupy' solutions: facts and misfacts. AB - 'Syrupy' solutions of liquid linear polyacrylamide (> or = 10%T, 0%C) appear to be excellent for fractionation of oligonucleotides and, potentially, for DNA sequencing. For such analyses, the silica wall must be coated by covalently bound strings of polyacrylamide; otherwise, the electroosmotic flow will slowly pump out the viscous electrolyte solution. Due to the enormous viscosity (100 Pa s for an 8% T solution) the polymer strings must be prepared in situ, by filling the capillary with the appropriate monomer solution. The reaction, however, cannot be driven to better than 80-85% conversion: in 10%T, the concentration of unreacted monomers will thus be 200-300 mM. This will give a substantial background absorbance (even at 254 nm) and leave a huge amount of potentially harmful reacting species in the background electrolyte. A chemical scavenging method is proposed here: after polymerization, a 100 mM solution of cysteine is driven in from the cathode and allowed to react for up to 10 h. At the end of the reaction period, the excess cysteine and its acrylamido adduct are driven out electrophoretically and the column is reconstituted with its normal background electrolyte. Columns thus preconditioned have been found to perform extremely well and to last as long as the inner coating (and the linear polymer filling) will last. No 'carry over' from run to run was experienced. PMID- 1459095 TI - Atrazine and simazine determination in river water samples by micellar electrokinetic capillary chromatography. AB - A rapid and sensitive micellar electrokinetic capillary chromatography analytical method was used for the determination of chlorotriazine herbicides in river water samples. Several electrolyte systems in the pH range 7-10 were tested in order to optimize the separation. The two compounds were separated in less than 10 min and the determination limit was about 0.4 ppb for each herbicide. Recovery values of the method were in the range 80%-117%. PMID- 1459096 TI - Applications of an automated apparatus for two-dimensional electrophoresis, Model TEP-1, for microsequence analyses of proteins. AB - Two-dimensional electrophoresis has become a rapid and powerful separation method for the preparation of samples for sequence analysis depending on the development of automated microsequencers accompanied by a blotting technique. We have constructed an automated apparatus for two-dimensional electrophoresis, Model TEP 1, which allows precise analytical runs under computer-control with a fully automated transfer from the first- to the second-dimensional gel. In the present paper we describe several applications of TEP-1 followed by blotting and sequencing to reveal the primary structure of proteins in a complex mixture. Several known and unknown proteins were analyzed. Enzymatic digests of proteins could be directly applied onto the TEP-1, in which a gel of lower molecular weight proteins was used as the second dimension. Subsequent blotting and sequencing provided internal sequence information. The use of TEP-1, followed by blotting, provides spots containing ca. 10-100 pmol protein. These figures permitted the identification of 10-40 amino acid residues from the N-terminus. The TEP-1 provides a simple and rapid separation of complex mixtures obtained from natural sources and chemical, biological or genetic products. PMID- 1459097 TI - Plasma protein map: an update by microsequencing. AB - The reference plasma protein map, obtained with immobilized pH gradients in the first dimension of two-dimensional electrophoresis, is presented. By microsequencing, more than 40 polypeptide chains were identified. The new polypeptides and previously known proteins are listed in a table and labeled on the protein map, thus providing an update of the human plasma two-dimensional gel database. PMID- 1459098 TI - Immune complexes in blood: a new strategy for the analysis of their antigen portion. AB - A method is described for the characterization of protein antigens from circulating immune complexes from plasma. Free immunoglobulins G were separated from larger immune complexes by gel filtration with a fast protein liquid chromatographic system. The collected immune complexes were dissociated with 4M urea into antigens and antibodies. With a second column run with 4M urea, antigens smaller than 120 kDa were separated from unloaded antibody fractions. After concentration, they were analyzed by two-dimensional gel electrophoresis. PMID- 1459099 TI - Protein synthesis in murine organs during postimplantation development detected by two-dimensional gel electrophoresis. AB - Mouse embryos were isolated from the uterus on days 10 to 11 of gestation and incubated in Dulbecco's modified Eagle's medium (DMEM) with [35S]methionine for 4 h. Subsequently, their hearts and the brains were dissected. The brain was divided into three parts, containing the telencephalon, mesencephalon, and myelencephalon. These tissues were then processed for two-dimensional (2-D) gel electrophoresis. Protein synthesis of the isolated tissues was analyzed for organ and cell lineage-specific patterns. We studied proteins with isoelectric points (pI) ranging from 4 to 10 and relative molecular weights (M(r)) varying from 10000 to 200000 and found several significant quantitative and qualitative differences between the tissues and the developmental stages analyzed. In particular, we were able to distinguish between protein spots that we now attribute putatively to the corresponding embryonic organs. These differences may reflect some of the organ- and cell lineage-specific changes in protein synthesis and gene expression during early mammalian differentiation. PMID- 1459100 TI - A human myocardial two-dimensional electrophoresis database: protein characterisation by microsequencing and immunoblotting. AB - This communication briefly describes how a human heart two-dimensional electrophoresis (2-DE) protein database is being established in our laboratory. The database contains more than 1500 polypeptides and approximately fifty proteins from 2-DE gels of human myocardial tissue have been characterised. Information about the proteins has been compiled including molecular weight (M(r)), isoelectric point (pI), sample spot (SSP) number, protein name, partial sequence, and antibody reacting with the protein. The first stage of this project involves the investigation of protein with pIs in the range pH 4-7. Future studies will employ immobilised pH gradient (IPG) gels as the first dimension of the 2-DE to examine basic proteins. The ultimate goal of this project is to establish a global picture of human heart protein expression in both normal and disease conditions. PMID- 1459101 TI - Electrophoretic analysis of electrically trained skeletal muscle. AB - Sheep latissimus dorsi muscle was electrically trained, thereby inducing fast-to slow fibre-type transformation. Using a combination of one- and two-dimensional gel electrophoresis techniques with computer analysis, we have analysed altered expression of contractile protein isoforms at protein and mRNA level over a time course of electrical training extending to 5 months. Myosin heavy chain and regulatory myosin light chain analysis showed predominant expression of their slow isoforms (86% and 92%, respectively) after 3 months of training. At the same time point, however, tropomyosin analysis revealed that the slow isoform of the alpha-subunit accounted for 64% of the total alpha expression. Troponin T isoform switching proceeded more slowly over the same time course than tropomyosin and the thick filament proteins studied. Troponin T analysis revealed 5 fast and 2 slow isoforms in the sheep, of which the second slow isoform only became clearly visible after 5 months' training. At this time point the two slow isoforms were more predominant than their fast counterparts. This suggests that a wide heterogeneity of fast and slow isoform combinations are possible in the thin filament of skeletal muscle. PMID- 1459102 TI - Towards a two-dimensional database of common human proteins. AB - A protein pattern of common human proteins was constructed by comparing the two dimensional gel electrophoresis (2-DE) protein patterns from five cell lines of different germ layers. Total cell lysate and the isolated and purified nuclei of each cell line were separated by parallel electrophoresis runs in a multiple casting system of highest reproducibility. The computerized image analysis of the digitized 2-DE gels revealed a master protein pattern for each cell line. By comparison of all master protein patterns a 2-DE protein map of only common human proteins was constructed as a basis for a new 2-DE database. In a first step we have started characterizing a number of spots by microsequencing, amino acid composition analysis, and mass spectroscopy. PMID- 1459103 TI - Examination of microheterogeneity in grass pollen allergens. AB - The separation of timothy pollen extract by two-dimensional immunoblotting revealed microheterogeneity of the major allergens PhI p I and PhI p V. There was not only a diversity in size, 38 and 32 kDa for PhI p V and 37, 35, and 33 kDa for PhI p I, but also a separation into proteins of identical sizes but different pIs. Since former studies on the protein structure by amino acid analysis and N terminal microsequencing did not reveal any differences, we examined other possibilities that might cause microheterogeneity. In allergens belonging to the PhI p I group, the variability in pI can be due to the carbohydrate structure and to the fact that charges are hidden in the interior of the protein, as shown by varying concentrations of urea. On the other hand we were not able to detect any such reasons for the existence of PhI p V isoallergens. Thus, we assume that they are stable conformational isomers of the proteins (allomorphism) or that there are only slight variations in the internal sequences of these proteins (polymorphism) causing distinct pIs. PMID- 1459104 TI - Identification of human myocard proteins separated by two-dimensional electrophoresis. AB - N-Terminal sequencing, internal sequencing and amino acid analysis were used to identify twelve proteins of the human myocard two-dimensional gel electrophoresis (2-DE) pattern. Amino acid analysis was shown to be a powerful tool in addition to sequencing. The identification of a disease-associated N-terminally blocked protein by internal sequencing was not successful. The twelve identified proteins are the basis of a human myocard 2-DE database. PMID- 1459105 TI - Using two-dimensional gel electrophoresis to study immune response against intracellular bacterial infection. AB - Principal component analysis was applied to two-dimensional (2-D) gel electrophoresis patterns, obtained in various phases of infection. Untreated controls could be satisfactorily differentiated from patterns after infection on days 3 and 7 whereas day 10 of infection was grouped with the controls. Comparison of host cellular protein patterns could help to classify in vivo developing infection without requiring any so-called immune marker functions. Immunoaffinity separation of infected cells treated with detergent, followed by 2 D electrophoresis of negative as well as positive eluates, did not reveal radiolabeled bacterial protein antigens. PMID- 1459106 TI - Effects of bile salt exposure on pancreatic duct barrier function and protein release determined by two-dimensional electrophoresis and lectin-affinoblotting. AB - We analyzed effects of a bile salt on pancreatic duct barrier function and protein release into pancreatic juice in cats, using two-dimensional electrophoresis and lectin-affinoblotting. Preanalyzed pancreatic juice was perfused along the pancreatic duct following duct exposure to a bile salt. In this case, pancreatic duct mucosa showed a partial loss of barrier function to the leakage of exocrine pancreatic proteins dependent upon molecular weight and charge. The release of a sialic acid possessing protein into pancreatic juice was observed. PMID- 1459107 TI - Application of high resolution two-dimensional polyacrylamide gel electrophoresis of polypeptides from cultured neonatal rat cardiomyocytes: regulation of protein synthesis by catecholamines. AB - High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was applied to cultured neonatal rat heart muscle cells, incubated for 72 h at 37 degrees C in serum-free medium, either in the absence or in the presence of 0.1 microM norepinephrine. After silver staining, about 340 and 550 protein spots could be seen in cardiomyocytes, cultured either in the absence or presence of norepinephrine. Of these spots, 141 could be further characterized according to isoelectric point and molecular weight, with 71 protein spots being present under both conditions. In cells cultivated in presence of norepinephrine, 58 new protein spots appeared, whereas 12 spots disappeared, and 22 spots increased (whereas 3 spots decreased) in intensity. In comparison with 2-D PAGE of rat cardiomyocytes, the protein pattern of the intact heart of neonatal rats is incongruent. 2-D PAGE of polypeptides of cultured neonatal rat cardiomyocytes may be a suitable tool to study the regulation of protein synthesis by various stimuli with relevance to cardiac growth adaptation, inotropy and heart failure. PMID- 1459108 TI - Regulation of protein biosynthesis in neonatal rat cardiomyocytes by adrenoceptor stimulation: investigations with high resolution two-dimensional polyacrylamide gel electrophoresis. AB - The role of alpha- and beta-adrenoceptor-mediated regulation of protein patterns in cultured neonatal rat cardiomyocytes was studied with high resolution two dimensional polyacrylamide gel electrophoresis. Spontaneously beating neonatal rat cardiomyocytes were cultured for 72 h at 37 degrees C in serum-free medium, supplemented with either the catecholamine norepinephrine (0.1 microM), or with norepinephrine (0.1 microM) plus the alpha 1-adrenoceptor blocker prazosin (1 microM), or with neither of these substances. In transmission light, 105 protein spots could be seen in the lysates from control cells, 244 spots were identified in lysates from norepinephrine-treated cells, and 114 protein species were counted in the case of lysates from cardiomyocytes which had been cultured in the presence of norepinephrine plus prazosin. This experimental approach allows a clear classification of alpha- and non-alpha (probably beta)-adrenoceptor mediated catecholamine effects on protein synthesis in cardiomyocytes. In comparison with previous experiments (Chang et al., Electrophoresis, this issue, pp. 748-754), less protein species were identified in the untreated control cardiomyocytes, as well as in the norepinephrine treated cells. The only actual modification in the experimental setup in these two series was the addition of dimethyl sulfoxide--a substance known for its repressive effect on oncoprotein expression--to the culture medium, as solvent for prazosin. PMID- 1459109 TI - Genetic variability of pepper (Capsicum annuum L.) seed proteins studied by 2-D electrophoresis with immobilized pH gradients. AB - Ten pepper (Capsicum annuum L.) inbred lines were successfully differentiated by two-dimensional electrophoresis with immobilized pH gradients. Qualitative polymorphism of water-soluble and urea/detergent-soluble seed proteins, respectively, was investigated by computer analysis and used for establishing a dendrogram derived from maximum-parsimony analysis. The dendrogram calculated from urea/detergent-soluble proteins shows four types of distance indices, whereas water-soluble proteins show two sets of inbred lines with similar intraset distance indices. The validity of the dendrograms with respect to quantitative inherited traits, such as cold tolerance and earliness, will be tested by field trials. PMID- 1459110 TI - Improved phenotyping of alpha 1-antichymotrypsin (ACT) by isoelectric focusing and immunoprinting: first demonstration of a deficient protein variant in the ACT system. AB - Genetic variation of human alpha 1-antichymotrypsin (ACT) was investigated in sera using thin-layer polyacrylamide gel isoelectric focusing (pH range 4.0-6.5) followed by immunoprinting with a monospecific anti-human ACT antibody. Sialidase treated samples showed a microheterogeneous banding pattern which consisted of two major and several additional minor components with isoelectric points between pH 5.0 and 5.3. A population study of 200 unrelated individuals from southern Germany revealed no genetic variation. In a clinical investigation, however, we found a unique banding pattern in a female patient suffering from chronic obstructive pulmonary disease. In comparison with the monomorphic normal type the detected variant phenotype shows two additional bands that have lower intensities and are located cathodically to their major bands. Inheritance of the deficient IEF variant "ACT Bochum" was confirmed by a family study. To our knowledge this is the first genetic ACT mutant to be observed at the protein level. PMID- 1459111 TI - Isoelectric focusing and immunoblotting of the platelet membrane glycoprotein complex IIb. IIIA following urea solubilization. AB - Effective solubilization of the major platelet membrane component, the glycoprotein IIb.IIIa complex, can be achieved with 8 M urea. By avoiding nonionic detergents in the separation medium it is possible to obtain clear immunoblot patterns without interference from the isoelectric focusing matrix. Upon running on a pH 4.25-5.25 immobilized pH gradient, immunoreactive bands corresponding to the nonreduced IIb.IIIa complex stain between pH 4.5 and 5.0. The method appears of significant potential utility in evaluating glycoprotein IIb.IIIa polymorphisms under different clinical conditions. PMID- 1459112 TI - Genetic study of orosomucoid by isoelectric focusing and immunoprinting in patients with carcinoma. AB - The carbohydrate moiety of the orosomucoid (ORM) molecule shows microheterogeneity [1] and the pteridine-containing variant seems to be tumor specific [2-4]. However, there also exists a genetic (protein-related) polymorphism coded by the ORM1 and ORM2 loci on chromosome 9 [5, 6]. To investigate the relationship between ORM1 gene products and the development of carcinoma, we analyzed the ORM1 phenotypes of desialated sera from 125 patients with carcinoma. The allele frequencies were estimated for ORM1*F1 0.556, ORM1*F2 0.012 and ORM1*S 0.432. In comparison to healthy individuals from the same geographical area [6] the ORM1 S phenotypes are significantly more frequent in carcinoma patients. The patients' sera frequently showed additional ORM-positive proteins which focused slightly cathodically to the ORM 2 A band. These proteins may represent posttranslational modifications of the ORM1*S allele product. Whether these modifications are tumor-specific and related to the carbohydrate moiety of the molecule must be confirmed in further studies. PMID- 1459113 TI - Qualitative and quantitative changes in barley seed protein patterns during the malting process analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with respect to malting quality. AB - Seeds of two barley cultivars, similar in total protein content and malt extract yield but different in their final attenuation values, were malted. Samples taken at daily intervals during the malting process were extracted sequentially with Tris-HCl buffer, aqueous 2-propanol, aqueous 2-propanol containing 0.5% dithiothreitol, and 4 M urea, containing 0.5% dithiothreitol and 1% Nonidet P-40. The protein composition of these extracts was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and computer densitometry to determine whether differences observed in the rate or extent of protein modification are related to the malting quality character final attenuation. It was found that, common to both cultivars, the albumin and globulin proteins were relatively resistant to proteolysis, whereas the hordeins suffered a dramatic breakdown during malting, with the D hordein being degraded most rapidly, followed by the B and C hordeins. Besides these similarities, differences between both cultivars were observed in the relative rates of D hordein degradation, as this rate was considerably higher in the cultivar with high malting quality. Similar, but much less distinct kinetics were seen with certain B hordeins. Since a possible relationship might exist between the rate of proteolysis of the D hordeins and the character final attenuation, we analyzed a larger number of barley cultivars with different final attenuation values with a simplified technique. For the ten cultivars examined, differences during germination were again seen in the rates of modification of the D hordeins. However, significant correlations between the D hordein breakdown and final attenuation values were not obtained, so that we propose that there exists at best a loose correlation between the relative rate of proteolysis of these proteins and the malting quality character final attenuation. PMID- 1459114 TI - Stress effects on hormonal growth factors in tobacco tissues indicated by special changes in the isoelectric peroxidase patterns. AB - The isoelectric peroxidase patterns of tobacco tissue cultures allow us to draw inferences to cell elongation and cell division because certain zones in acid pH ranges respond to the influence of auxines and gibberellins (promoting cell elongation) and others respond to the influence of cytokinins (promoting cell division). Stress, due to the absence of phosphate and presence of lead in the medium, causes characteristic changes in the intensity of these sensitive zones in peroxidase patterns. It may be deduced that the increase and decrease of these zones correspond to stimulation and inhibition of cell elongation and cell division, respectively. Cell elongation remains almost unaltered by lack of phosphate but is markedly inhibited by lead, while cell division is enhanced. However, stress brings about a reduction of dry weight. Reactions to stress can be observed earlier in patterns of peroxidase than in growth. PMID- 1459115 TI - Wheat gliadin: digital imaging and database construction using a 4-band reference system of agarose isoelectric focusing patterns. AB - An isoelectric focusing method using thin-layer agarose gel has been developed for wheat gliadin. Using flat-bed units with a third electrode, up to 72 samples per gel may be analyzed. Advantages over traditional acid polyacrylamide gel electrophoresis methodology include: faster run times, nontoxic media, and greater sample capacity. The method is suitable for fingerprinting or purity testing of wheat varieties. Using digital images captured by a flat-bed scanner, a 4-band reference system using isoelectric points was devised. Software enables separated bands to be assigned pI values based upon reference tracks. Precision of assigned isoelectric points is shown to be on the order of 0.02 pH units. Captured images may be stored in a computer database and compared to unknown patterns to enable an identification. Parameters for a match with a stored pattern may be adjusted for pI interval required for a match, and number of best matches. PMID- 1459116 TI - Discontinuous electrophoresis of beta-caseins for the determination of bovine caseins in milk and dairy products. AB - Discontinuous acidic anodic polyacrylamide gel electrophoresis enables the separation of bovine beta-caseins from those of ovine and caprine. Interfering protein bands as a consequence of ripening or processing have not been detected. After evaluation of the stained gel by laser densitometry, quantification was performed with calibration standards on the same gel by the ratio of the peak areas from bovine to ovine and bovine to caprine, respectively. Thus, independence from the extractability of proteins affected by denaturation and ripening (which might in some cases raise the limit of detection) is achieved. The range of quantification extends from 5 to approximately 70% bovine casein in relation to total casein. PMID- 1459117 TI - Fish species identification by peptide mapping of the myosin heavy chain. AB - Fish species of seafood made of washed fish flesh (e.g. imitation crab meat from surimi) were identified by peptide mapping of the myosin heavy chain (MHC). In the first step the MHC was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in 7.5% T gel, followed by a second SDS-PAGE in a 15% T gel with proteolytic digestion of the MHC in the gel. The resulting peptides gave species specific patterns. PMID- 1459118 TI - Characterization of endopolygalacturonase (EC 3.2.1.15) from Aspergillus niger as glycoprotein by electrophoretic methods and lectin affino-blotting. AB - Chromatographically purified endopolygalacturonase (PG) from Aspergillus niger was deglycosylated with N-glycosidase F (PNGase F) and characterized by means of sodium dodecyl sulfate (SDS)-electrophoresis, polyacrylamide gel electrophoresis (PAGE) without denaturing agents, isoelectric focusing (IEF) and lectin affino blotting. The results show that PG, which is apparently homogeneous in SDS-PAGE but heterogeneous in IEF and PAGE, consists of at least two polypeptide chains with different glycosylation patterns. The component with the higher electrophoretic mobility is deglycosylated with PNGase F and reacts with concanavalin A (Con A) and Galanthus nivalis agglutinin (GNA), indicating a "high mannose" or "hybrid"-type of glycoprotein (GP). The other component may contain O glycosidically linked mannose, N-acetylglucosamine or glucose. PMID- 1459119 TI - An outbreak of gentamicin-resistant Klebsiella bacteraemia at a children's hospital. AB - An outbreak of Klebsiella bacteraemia at the Ethio-Swedish Childrens' Hospital, Addis Abeba, Ethiopia is described. The epidemic occurred between February 1988 and February 1990 and appeared to originate in the neonatal nursery and subsequently spread to involve other wards in the hospital. Resistance to several antibiotics, including gentamicin, was common. The importance of effective surveillance and the early institution of control measures for the prevention of nosocomial infection are discussed. PMID- 1459120 TI - Relapsing fever in children--demographic, social and clinical features. AB - Louse-borne relapsing fever (LBRF) is an acute febrile illness endemic Ethiopia. To date reports of childhood LBRF are few. The demographic, social and clinical features of eighty children with LBRF admitted to Ethio-Swedish Children's Hospital, Addis Abeba between 1989 and 1991 is presented. The mean age of patients was 8.8 years (range 4 months to 15 years). The male to female ratio was 1.2:1. Seventy-seven (97%) patients came from Addis Abeba. They came from poor families living in overcrowded homes. Fever, headache, right upper quadrant pain, chills and rigors were common symptoms. Fever and hepatosplenomegaly were common signs. Three drug regimens were used in the treatment of patients. A combination of penicillin and tetracycline, chloramphenicol alone and erythromycin alone, all given for 3 days. There was only one death. The literature on LBRF in adults is reviewed and the results are compared (1). PMID- 1459121 TI - National tuberculin test survey in Ethiopia. AB - To plan and implement an effective National Tuberculosis Control Programme, it is essential to know the incidence of tuberculosis. Thus a tuberculin survey was conducted in Ethiopia between December 1987 and April 1990. A sample of 55 children, aged 6 to 10 years was selected from each of 480 representative clusters from 16 weredas (districts), which were chosen randomly. A total of 26,529 children were given intradermal tuberculin test and the results read in 26,269. There were 23,595 children who had no BCG vaccination of whom 2,503 (10.6%) were positive; this gives a "risk of infection" of 1.4% which is lower than the 3.0% reported for the same age group during the tuberculin survey in 1953-1955, suggesting that there has been a reduction in the tuberculin test positivity rate. PMID- 1459122 TI - Bronchial asthma in Jima: a prospective analysis of 204 patients. AB - Two hundred and four (204) consecutive adult asthmatic patients who visited the outpatient clinic of Jima Institute of Medical Sciences from May 1 to August 30, 1989 were prospectively studied. Data on age, sex, ethnic distribution and the associated etiological factors were documented. The age range was from 17-75 (mean 33.4) years and the male to female ratio was 1.4:1. The majority (80%) were not members of the ethnic group indigenous to the area. Of the total, 175 (85%) were not natives of Jima town and its surroundings. One hundred and fifty (85.7%) of the latter developed the disease in Jima. Ninety-six (64%) of the 150 patients contracted the disease in less than 5 years of their stay in the area. Infections, emotional stress, dust, and weather changes were the main precipitating factors. The majority of the attacks occurred from June to October. Allergic rhinitis was present in 88% of the patients and atopic dermatitis in 3%. Forty-one (20%) patients had a family history of asthma. Forty-eight percent of the patients claimed that change of climate relieved their symptoms. Eosinophilia was documented in 51.5% and parasitic infestations were observed in 39% of patients. The study shows that a variety of environmental factors such as pollen dust, fungus and climatic changes play a major role and may account for the high performance of asthma in Jima town. It is recommended that further studies be conducted to find out the causative factors so that appropriate preventive measures can be implemented. PMID- 1459123 TI - Chylous mesenteric and retroperitoneal cysts of developmental origin amongst Ethiopians: report of four cases. AB - Chylous mesenteric and retroperitoneal cysts of developmental origin are unusual and rarely diagnosed with accuracy before laparotomy. They may produce compression of viscera and may rupture with haemorrhage. This is the first report of four cases, with varied presentations, from an African country. PMID- 1459124 TI - The effect of driving force on intramolecular electron transfer in proteins. Studies on single-site mutated azurins. AB - An intramolecular electron-transfer process has previously been shown to take place between the Cys3--Cys26 radical-ion (RSSR-) produced pulse radiolytically and the Cu(II) ion in the blue single-copper protein, azurin [Farver, O. & Pecht, I. (1989) Proc. Natl Acad. Sci. USA 86, 6868-6972]. To further investigate the nature of this long-range electron transfer (LRET) proceeding within the protein matrix, we have now investigated it in two azurins where amino acids have been substituted by single-site mutation of the wild-type Pseudomonas aeruginosa azurin. In one mutated protein, a methionine residue (Met44) that is proximal to the copper coordination sphere has been replaced by a positively charged lysyl residue ([M44K]azurin), while in the second mutant, another residue neighbouring the Cu-coordination site (His35) has been replaced by a glutamine ([H35Q]azurin). Though both these substitutions are not in the microenvironment separating the electron donor and acceptor, they were expected to affect the LRET rate because of their effect on the redox potential of the copper site and thus on the driving force of the reaction, as well as on the reorganization energies of the copper site. The rate of intramolecular electron transfer from RSSR- to Cu(II) in the wild-type P. aeruginosa azurin (delta G degrees = -68.9 kJ/mol) has previously been determined to be 44 +/- 7 s-1 at 298 K, pH 7.0. The [M44K]azurin mutant (delta G degrees = -75.3 kJ/mol) was now found to react considerably faster (k = 134 +/- 12 s-1 at 298 K, pH 7.0) while the [H35Q]azurin mutant (delta G degrees = -65.4 kJ/mol) exhibits, within experimental error, the same specific rate (k = 52 +/- 11 s-1, 298 K, pH 7.0) as that of the wild-type azurin. From the temperature dependence of these LRET rates the following activation parameters were calculated: delta H++ = 37.9 +/- 1.3 kJ/mol and 47.2 +/- 0.7 kJ/mol and delta S++ = -86.5 +/- 5.8 J/mol.K and -46.4 +/- 4.4 J/mol.K for [H35Q]azurin and [M44K]azurin, respectively. Using the Marcus relation for intramolecular electron transfer and the above parameters we have determined the reorganization energy, lambda and electronic coupling factor, beta. The calculated values fit very well with a through-bond LRET mechanism. PMID- 1459125 TI - Characterization of peptides related to neuropeptide tyrosine and peptide tyrosine-tyrosine from the brain and gastrointestinal tract of teleost fish. AB - Neuropeptide Y was isolated from the brain of the Atlantic cod, Gadus morhua and its primary structure established as Tyr-Pro-Ile*-Lys-Pro-Glu*-Asn-Pro-Gly-Glu10 Asp-Ala-Pro-Ala-Asp*-G lu*-Leu*-Ala- Lys*-Tyr20-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile Asn-Leu30-Ile-Thr -Arg-Gln-Arg-Tyr- CONH2. Residues denoted by an asterisk are different from the corresponding sequence of human neuropeptide Y. A structurally similar peptide was isolated from the brain of the trout, Oncorhynchus mykiss. Trout neuropeptide Y contains four substitutions (Ile3-->Val, Ala14-->Thr, Asp15- >Glu and Ser22-->Thr) compared with cod neuropeptide Y. A second peptide of the neuropeptide Y family was identified in the trout brain and this component was structurally similar to peptide tyrosine-tyrosine previously isolated from frog intestine (six amino acid substitutions) and identical to a peptide isolated from the pancreas of the closely related species, Oncorhynchus kisutch (Coho salmon). Peptide tyrosine-tyrosine, with the same primary structure as the brain peptide, was also isolated from an extract of the trout stomach. The data indicate that a peptide analogous to mammalian neuropeptide Y is present in the brain of teleost fish and a peptide analogous to mammalian peptide tyrosine-tyrosine is present in brain, gastrointestinal tissue and pancreas. We speculate, therefore, that the putative gene duplication that led to pancreatic polypeptide in the higher vertebrates took place after the time of divergence of fish and tetrapods. PMID- 1459126 TI - Substitution of Arg214 at the substrate-binding site of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. AB - The gene encoding p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens was cloned in Escherichia coli to provide DNA for mutagenesis studies on the protein product. A plasmid containing a 1.65-kbp insert of P. fluorescens chromosomal DNA was obtained and its nucleotide sequence determined. The DNA-derived amino acid sequence agrees completely with the chemically determined amino acid sequence of the isolated protein. The enzyme is strongly expressed under influence of the vector-encoded lac promotor and is purified to homogeneity in a simple three-step procedure. The relation between substrate binding, the effector role of substrate and hydroxylation efficiency was studied by use of site-directed mutagenesis. Arg214, in ion-pair interaction with the carboxy moiety of p-hydroxybenzoate, was replaced with Lys, Gln and Ala, respectively. The affinity of the free enzymes for NADPH is unchanged, whereas the affinity for the aromatic substrate is strongly decreased. For enzymes Arg214-->Ala and Arg214-->Gln, the effector role of substrate is lost. For enzyme Arg214-->Lys, binding of p-hydroxybenzoate highly stimulates the rate of flavin reduction. In the presence of substrate or substrate analogues, the reduced enzyme Arg214-->Lys fails to stabilize the 4 alpha-hydroperoxyflavin intermediate, essential for efficient hydroxylation. Like the wild-type, enzyme Arg214-->Lys is susceptible to substrate inhibition. From spectral and kinetic results it is suggested that secondary binding of the substrate occurs at the re side of the flavin, where the nicotinamide moiety of NADPH is supposed to bind. PMID- 1459127 TI - Purification, properties and primary structure of thioredoxin from Aspergillus nidulans. AB - This paper reports the purification and the properties of a thioredoxin from the fungus Aspergillus nidulans. This thioredoxin is an acidic protein which exhibits an unusual fluorescence emission spectrum, characterized by a high contribution of tyrosine residues. Thioredoxin from A. nidulans cannot serve as a substrate for Escherichia coli thioredoxin reductase. Corn NADP-malate dehydrogenase is activated by this thioredoxin in the presence of dithiothreitol, while fructose 1,6-bisphosphatase is not. The amino acid sequence of Aspergillus thioredoxin was determined by automated Edman degradation after cleavage with trypsin, SV8 protease, chymotrypsin and cyanogen bromide. The masses of tryptic peptides were verified by plasma-desorption mass spectrometry. The mass of the protein was determined by electrospray mass spectrometry and shown to be in agreement with the calculated mass derived from the sequence (M(r) = 11,564). Compared to thioredoxins from other sources, the protein from A. nidulans displays a maximal sequence similarity with that from yeast (45%). PMID- 1459128 TI - Subtilisin removes the surface layer of the phage fd coat. AB - The major coat protein of native filamentous phage fd is vulnerable to digestion by subtilisin, but not by any of a number of other proteolytic enzymes. Degradation by the non-specific protease subtilisin occurs at specific sites in the N-terminal portion of g8p. The N-terminal part of the protein is considered to be the outer layer of a two-layered coat. Thus, subtilisin treatment results in a monolayered phage particle. These particles possess the morphology and stability of native phage fd. Furthermore, subtilisin proteolysis proved to be an efficient instrument in detecting variations in the topology of the g8p of related filamentous phages. PMID- 1459129 TI - Analysis of the isoleucyl-tRNA synthetase reaction by total rate equations. Magnesium and spermidine in the tRNA kinetics. AB - Derivation of a steady-state rate equation for the aminoacyl-tRNA synthetases is described, and its suitability for the analysis of various details of the reaction is tested. The equation is applied to the magnesium and spermidine dependences of the isoleucyl-tRNA synthetase reaction. Earlier work [Airas, R.K. (1990) Eur. J. Biochem. 192, 401-409] is expanded by experiments and calculations of the tRNA kinetics. The analysis suggests the following new details in addition to the earlier results: (a) The binding of tRNA to the enzyme (and not only the rate of the aminoacylation reaction) is affected by the presence of the Mg2+ and spermidine in the tRNA molecule. At least two bound Mg2+ or spermidines are required. (b) tRNA and PPi partly inhibit the binding of each other to the enzyme. (c) The transfer reaction is rather slow, and, at least under some conditions, it participates in rate limitation. (d) A Mg(2+)-induced reduction in the aminoacylation rate seems to be directed to the dissociation of the aminoacyl tRNA from the enzyme. This dissociation rate is enhanced if a Mg2+ is first dissociated from the enzyme or tRNA. An increase in the Mg2+ concentration shifts the rate limitation from the transfer reaction towards dissociation of the product. PMID- 1459130 TI - Effect of inorganic pyrophosphate on the pretransfer proofreading in the isoleucyl-tRNA synthetase from Escherichia coli. AB - A total rate equation was used to calculate the discrimination of valine by the isoleucyl-tRNA synthetase from Escherichia coli. The PPi present in the cell makes the backward reaction or the pyrophosphorolysis of the E.aa-AMP possible. If the E.Ile-AMP has been corrected for wrong aminoacyl adenylation by the pretransfer proofreading, the pyrophosphorolysis rapidly equilibrates the corrected E.Ile-AMP with E.Ile and thus spoils the effect of the proofreading. The loss of the corrected species is avoided if there is a barrier (perhaps conformational) formed by a slow reaction step between the noncorrected E.Ile-AMP and the corrected (*E)tRNA(Ile-AMP). If such a slow conformational change exists, the increase in accuracy from the pretransfer proofreading would be beneficial, and, in addition, the PPi increases the accuracy by optimizing the initial discrimination of the wrong amino acid. PMID- 1459131 TI - Mechanism of carboxypeptidase-Y-catalysed peptide semisynthesis. AB - The initial rate steady-state kinetics of carboxypeptidase-Y-catalyzed hydrolysis and aminolysis reactions with some alpha-N-benzoyl-L-tyrosinyl compounds has been investigated using L-valinamide as the nucleophile in aminolysis. Hydrolysis of alpha-N-benzoyl-L-tyrosinyl ethyl ester, 4-nitroanilide, and -amide has been studied in the pH range 4-9. The results are interpreted in terms of the classical serine proteinase mechanism, which involves enzyme-substrate complex formation, followed by acylation and deacylation of the enzyme. The three reactions share the same deacylation step. It is rate-determining with the ester substrate, but with the 4-nitroaniline acylation is and this is even more pronounced with the amide. From the pH dependencies, no change of rate determining step is apparent in the range pH 4-9. For the 4-nitroanilide and the amide substrates, the kinetic parameter, Kc/Km, is influenced by an ionizing group with a pK value of 6. Probably this is the active-site histidine residue, which thus is active in acylation in its deprotonated form. That group affects the deacylation reaction similarly as seen from the kinetics of the ester substrate. Aminolysis occurs in parallel to hydrolysis in the presence of reactive nucleophiles. Here L-valinamide was used as model nucleophile. The analysis of the observed kinetic effects of L-valinamide on the initial rate behaviour of carboxypeptidase-Y-catalyzed hydrolysis reactions suggests a reaction mechanism which involves (a) the binding of the free nucleophile to the free enzyme and (b) reaction of the free nucleophile with the acyl-enzyme complex forming an enzyme-aminolysis product complex, which dissociates into the free enzyme and the aminolysis product. The reactions are characterized by a number of kinetic parameters, the values of which are determined. The results of aminolysis progress reactions indicate that the formation of the product in high yields is strongly dependent on the leaving group of the substrate. The initial production of aminolysis product, however, is the same for the three substrates. But the fact that their Kc/Km values differ by several orders of magnitude leads to significantly different progresses of the aminolysis. The ester substrate is the only one that efficiently competes with and hinders the hydrolysis of the aminolysis product. PMID- 1459132 TI - Purification and properties of a novel arylmalonate decarboxylase from Alcaligenes bronchisepticus KU 1201. AB - A novel decarboxylase which catalyzes an enantioselective decarboxylation of alpha-aryl-alpha-methylmalonates to alpha-arylpropionates has been purified from a soil bacterium Alcaligenes bronchisepticus KU 1201. The enzyme was purified 300 fold to homogeneity, judged from the analysis of N-terminal amino acid sequence, and found to be a monomeric enzyme of apparent 24 kDa. The enzyme catalyzes a decarboxylation giving alpha-arylalkanoates from substituted malonates such as alpha-arylmalonate and alpha-alkyl-alpha-arylmalonates. The decarboxylase is not a biotin containing enzyme because avidin have no influence on the enzyme activity. In addition, the enzyme does not require known co-factors (ATP, ADP and coenzyme A) for maximum activity. The enzyme activity was inhibited by sulfhydryl agents. The electronic effect of the substituents on kcat for the enzymic decarboxylation of arylmalonates has been studied. The logarithm of relative value of kcat gave a linear correlation to Hammett's sigma with a rho value of +1.9, for substituted phenylmalonates. Comparing the relative activities, it is clear that the enzyme prefers alpha-arylmalonates to alpha-aryl-alpha methylmalonates. Thus, the enzyme was tentatively named as arylmalonate decarboxylase. PMID- 1459133 TI - Regulation of vimentin expression in cultured epithelial cells. AB - Most cell types start expressing vimentin when brought into tissue culture. Using both vimentin-expressing (HeLa) and vimentin-negative (MCF-7) epithelial cell lines, we have identified the cis-regulatory DNA elements involved in this process. Sequences located 1.1-0.6 kb upstream of the vimentin transcription initiation site strongly enhance expression in HeLa cells, but are silenced in MCF-7 cells. Other regulatory elements in the vimentin promoter (an enhancer 3.2 2.6 kb upstream and a minimal promoter region including the CAAT-box) are potentially active in both cell types, but are silenced by the 0.5-kb fragment in MCF-7 cells. Deletion of this fragment restores transcriptional activity of a transfected vimentin promoter. Our data indicate that a double AP 1/jun-binding site present in the 0.5-kb fragment mediates the induction of vimentin expression in cultured epithelial cells, while silencing sequences located within the same fragment are responsible for the absence of vimentin expression in MCF-7 cells. In contrast to MCF-7 cells, a transfected vimentin promoter and gene are transcriptionally active in the vimentin-negative epithelial cell line T24. Transfection studies show that type-III-intermediate-filament expression is not impaired at any level in these cells. Upon transfection and expression of a desmin construct in T24 cells not only desmin, but also vimentin was detected. Both proteins assembled into intermediate filaments. This induction of vimentin expression appeared to be regulated at the post-transcriptional level. PMID- 1459134 TI - Regulatory phosphorylation of phosphoenolpyruvate carboxylase in protoplasts from Sorghum mesophyll cells and the role of pH and Ca2+ as possible components of the light-transduction pathway. AB - The light-dependent phosphorylation of the photosynthetic phosphoenolpyruvate carboxylase (PyrPC) was shown to occur in protoplasts from Sorghum mesophyll cells. It was accompanied by an increase in PyrPC protein-serine-kinase activity and conferred the target-specific functional properties, i.e. an increase in Vmax and apparent Ki for L-malate, as previously found with the whole leaf. The light dependent regulatory phosphorylation of PyrPC was (a) specifically promoted by the weak bases NH4Cl and methylamine (agents which increase cytosolic pH), but not by KNO3, (b) inhibited by the cytosolic protein-synthesis inhibitor, cycloheximide, thus confirming that protein turnover is a component of the signal transduction cascade, as reported in [4], (c) found to moderately decrease in the presence of EGTA and to be strongly depressed when the Ca(2+)-selective ionophore A23187 was added to the incubation medium together with EGTA. Addition of Ca2+, but not of Mg2+, to the Ca(2+)-depleted protoplasts partially, but significantly, relieved the inhibition. Calcium deprivation apparently affected the in-situ light-activation of the PyrPC protein kinase. These data indicated that both Ca2+ and an increase in cytosolic pH are required for the induction of PyrPC protein kinase activity/PyrPC phosphorylation in illuminated protoplasts from Sorghum mesophyll cells. PMID- 1459136 TI - Zinc-specific activation of a HeLa cell nuclear protein which interacts with a metal responsive element of the human metallothionein-IIA gene. AB - Transcription of metallothionein genes is activated by heavy metals such as zinc and cadmium, and a DNA element called metal responsive element (MRE) is essential for this process. By mobility-shift assay, we identified a HeLa-cell nuclear protein which specifically binds to MREa of human metallothionein-IIA gene. This protein, named ZRF (zinc-regulatory factor), is present in the cells untreated with heavy metals. Zinc is essential for, and increases in a dose-dependent manner, the binding of ZRF to MREa. Other heavy metals which can also induce metallothioneins, including cadmium, copper and mercury, do not activate ZRF. A MREa-containing oligonucleotide that can bind ZRF confers heavy metal inducibility to a heterologous promoter, suggesting that ZRF is a zinc-dependent transcriptional activator. In addition to the MRE core sequence, the surrounding sequences are also important for both ZRF binding in vitro, and zinc-dependent transcriptional activation in vivo. MREa by itself responds not only to zinc but also to other metallothionein-inducing heavy metals, indicating that the ZRF protein, not the MREa sequence, is responsible for the zinc specificity. PMID- 1459135 TI - Analysis of soluble human and mouse interferon-gamma receptors expressed in eukaryotic cells. AB - The extracellular domains of the human and mouse interferon-gamma receptors were produced in insect Spodoptera frugiperda cells infected with recombinant baculoviruses and in mammalian Chinese-hamster-ovary cells. The receptors expressed in both systems are secreted into the culture medium. Their signal peptides are cleaved off and the proteins show heterogeneity in glycosylation which, however, does not affect the capacity to bind interferon gamma or specific antibodies. The soluble mouse receptors exhibit binding capacities similar to those of cell-surface-anchored receptors, whereas the human receptors exhibit a lower binding capacity. All soluble receptors inhibit the binding of interferon gamma to cellular receptors and neutralize the antiviral activity exerted by interferon gamma. These receptors could therefore be useful for structure/function analyses and in vivo studies. PMID- 1459137 TI - Allosteric characteristics of GTP cyclohydrolase I from Escherichia coli. AB - The kinetic and regulatory properties of GTP cyclohydrolase I were investigated using an improved enzyme assay and direct determination of the product, dihydroneopterin triphosphate. The enzyme was purified from Escherichia coli to absolute homogeneity as demonstrated by N-terminal sequencing of up to 50 amino acid residues. A 30-residue internal fragment showed 42% similarity with rat liver GTP cyclohydrolase I. The enzyme did not obey Michaelis-Menten kinetics or show a sigmoid reaction curve. The substrate saturation kinetics were found to be slow with low response to minor changes in GTP concentrations. GTP cyclohydrolase I has a relatively high apparent Km. The values are slightly different for enzyme purified by GTP-agarose (100 microM) and UTP-agarose (110 microM). Low turnover numbers of 12/min and 19/min were calculated for the respective enzyme preparations. GTP-cyclohydrolase-I activity was modulated in Vmax by K+, divalent cations, UTP and tetrahydrobiopterin. Divalent cations, such as Mg2+, had an activating effect with an optimum at 8 mM Mg2+. A different catalytic function and formation of a new, unidentified product by GTP cyclohydrolase I was observed in the presence of Ca2+. In the presence of 1 mM EDTA and Mg2+, GTP cyclohydrolase-I activity was strongly inhibited by chelate complexes. UTP proved not to be a competitive inhibitor, but a positive modulator. The inhibition by chelate complexes was totally abolished by UTP. Tetrahydrobiopterin showed an inhibitory effect, with 50% inhibition at 100 microM tetrahydrobiopterin. UTP was able to reduce the inhibition by tetrahydrobiopterin. Using monoclonal antibody 1F11 (related to the GTP-binding site), and monoclonal antibody NS7 (mimicking tetrahydrobiopterin), different binding sites were demonstrated for GTP and tetrahydrobiopterin on each enzyme subunit. Western-blot competition analysis revealed a UTP-binding site different from the binding sites of GTP and tetrahydrobiopterin. Based on the kinetic behaviour and the kind of modulations observed we defined GTP cyclohydrolase I as an M-class allosteric enzyme. PMID- 1459139 TI - Effects of chemical modification of Anabaena flavodoxin and ferredoxin-NADP+ reductase on the kinetics of interprotein electron transfer reactions. AB - The influence of chemical modification of arginine residues (using phenylglyoxal) in ferredoxin-NADP+ reductase (FNR), and of carboxyl groups (using glycine ethyl ester) in flavodoxin (Fld), on the kinetics of electron transfer between FNR and Fld, and between ferredoxin (Fd) and FNR, was examined using laser flash photolysis methods. All proteins were obtained from the cyanobacterium Anabaena PCC7119. Reduction by laser-generated 5-deazariboflavin semiquinone of the FAD moiety of phenylglyoxal-modified FNR occurred with a second-order rate constant 2.5-fold smaller than that obtained for reduction of native FNR, indicating either a small degree of steric hindrance of the cofactor, or a decrease in its redox potential, upon chemical modification. In contrast, no changes were found in the kinetics of reduction of the FMN cofactor of Fld modified by glycine ethyl ester as compared with the native protein. The observed rate constants for reoxidation of Fdred (reduced Fd) by FNRox (oxidized FNR) were dramatically decreased (approximately 100-fold) when phenylglyoxal-modified FNR was used. In contrast to the reaction involving the native proteins, no ionic strength effects on kobs values were found. These results, and those obtained upon varying the protein concentration, indicate that the rate constant for complex formation and the attractive electrostatic interaction between the two proteins were greatly diminished by chemical modification of arginine residues of FNR. When phenylglyoxal-modified FNRsq (FNR semiquinone) was used to reduce Fldox (oxidized Fld), similar inhibitory effects were observed. In this case, the limiting first order rate constant for Fldsq (Fld semiquinone) formation via intracomplex electron transfer from FNRsq was approximately 12-fold smaller than that obtained for the native FNR (600 s-1 vs 7000 s-1). Again, ionic strength effects were diminished. The glycine-ethyl-ester-modified Fld yielded a limiting first-order rate constant for intracomplex electron transfer from FNRsq to Fldox which was approximately 7-fold smaller (1000 s-1) than that obtained with native Fld, and ionic strength effects were again diminished. These results indicate that complex formation can still occur between modified FNR and native Fld, and between native FNR and modified Fld, but that the geometry of these complexes is altered so as to decrease the effectiveness of interprotein electron transfer. The results are discussed in terms of the specific structural features of the proteins involved. PMID- 1459138 TI - Molecular mimicry of trifluoroacetylated human liver protein adducts by constitutive proteins and immunochemical evidence for its impairment in halothane hepatitis. AB - A monospecific antibody (anti-CF3CO antibody) was obtained by affinity chromatography on a N epsilon-trifluoroacetyl-L-lysine (CF3CO-Lys) matrix of a rabbit polyclonal antiserum, directed against trifluoroacetylated protein adducts (CF3CO-proteins). The anti-CF3CO antibody recognized distinct CF3CO-proteins on immunoblots of a liver biopsy obtained from a human individual 10 h after halothane anaesthesia. Cross-reactive proteins of 52 kDa and 64 kDa were recognized on immunoblots of livers obtained from human individuals not exposed to halothane. Recognition of both CF3CO-proteins and the 52-kDa and 64-kDa cross reactive proteins was abolished in the presence of 1 mM CF3CO-Lys. Anti-CF3CO antibody, affinity-adsorbed to the 52-kDa or the 64-kDa cross-reactive proteins of human liver, recognized the majority of target CF3CO-proteins on immunoblots of the human liver biopsy of an individual exposed to halothane. Liver biopsies of 5 out of 7 (71%) patients with halothane hepatitis exhibited an absence or low amounts of immunorecognizable 52-kDa and/or 64-kDa cross-reactive proteins. In contrast, of 22 control human individuals tested, all liver tissue samples were positive for the 52-kDa and/or the 64-kDa cross-reactive proteins. These data indicate that epitopes on the cross-reactive proteins of 52 kDa and 64 kDa of human liver bear strong immunochemical resemblance to epitopes on human liver CF3CO-proteins. Low-level expression of the cross-reactive proteins of 52 kDa and 64 kDa is discussed as one possible factor in human susceptibility to halothane hepatitis. PMID- 1459140 TI - Binding of Bacillus sphaericus binary toxin to a specific receptor on midgut brush-border membranes from mosquito larvae. AB - The presence of specific receptors for Bacillus sphaericus binary toxin on brush border membrane fractions (BBMF) from Culex pipiens larvae midgut cells was demonstrated by an in vitro binding assay. Both activated and radiolabelled polypeptides from the 51-kDa and 42-kDa binary toxin of B. sphaericus 1593 specifically bound to BBMF. Direct binding and homologous competition experiments indicated a single class of B. sphaericus toxin receptors, with a dissociation constant (Kd) of approximately 20 nM and a maximum binding capacity (Bmax) of approximately 7 pmol/mg BBMF protein. The sugars GalNAc, GlcNAc and N-acetyl neuraminic acid had no detectable inhibitory effect on toxin binding to C. pipiens BBMF. Binding experiments with the non-susceptible mosquito species Aedes aegypti failed to detect significant binding of B. sphaericus binary toxin to A. aegypti BBMF. PMID- 1459141 TI - Non-lysosomal degradation of misfolded human lysozymes with and without an asparagine-linked glycosylation site. AB - Human lysozyme is a monomeric secretory protein composed of 130 amino acid residues, with four intramolecular disulfide bonds and no oligosaccharides. In this study, a mutant protein, [Ala128] lysozyme, which cannot fold because it lacks a disulfide bond, Cys6-Cys128, was expressed in mouse fibroblasts and was found to be mostly degraded in the cells, whereas the control wild-type lysozyme was quantitatively secreted into the media. The degradation of [Ala128]lysozyme was independent of the transport from the endoplasmic reticulum to the Golgi apparatus. The degradation was greatly inhibited by incubation of cells at 15 degrees C, but was minimally affected by treatment of cells with the lysosomotropic agent, chloroquine, implying a non-lysosomal process. Additional mutations (Gly48-->Ser or Met29-->Thr) were created to make asparagine-linked (N linked) glycosylation site in the [Ala128]lysozyme, and the resultant double mutants, [Ser48, Ala128]lysozyme and [Thr29, Ala128]lysozyme, were analyzed with respect to their intracellular degradation. These mutant proteins were susceptible to N-linked glycosylation, and were degraded in a similar manner to that of [Ala128] lysozyme, except that the onset of degradation of [Ser48, Ala128]lysozyme and [Thr29, Ala128] lysozyme, but not of [Ala128]lysozyme, was preceded by a lag period of up to 60 min. Furthermore, the degradative double mutants, [Ser48, Ala128]lysozyme and [Thr29, Ala128]lysozyme, were glycosylated post-translationally as well as co-translationally. These observations suggest that there is some interaction between the mechanisms of glycosylation and degradation. PMID- 1459142 TI - Oleate stimulation of diacylglycerol formation from phosphatidylcholine through effects on phospholipase D and phosphatidate phosphohydrolase. AB - Hydrolysis of exogenous phosphatidylcholine (PtdCho) to 1,2-diacylglycerol by rat liver plasma membranes was stimulated by oleate concentrations as low as 0.1 mM. In the presence of 75 mM ethanol, the fatty acid also enhanced phosphatidylethanol (PtdEtOH) formation from PtdCho. These effects were also observed with linoleate and arachidonate, but not with saturated fatty acids or detergents, and were minimal in microsomes or mitochondria. Release of [3H]choline from exogenous Ptd[3H]Cho was stimulated by oleate, whereas phosphoryl[3H]choline formation was inhibited. Oleate and other unsaturated, but not saturated, fatty acids also stimulated the conversion of exogenous [14C]phosphatidic acid to [14C]diacylglycerol. These data are consistent with stimulatory effects of these fatty acids on both phospholipase D and phosphatidate phosphohydrolase in liver plasma membranes. The stimulatory effect of guanosine 5'-O-[3-thio]triphosphate) (20 microM) on PtdEtOH and diacylglycerol formation from PtdCho was enhanced by low concentrations of oleate. Phospholipase A2 also stimulated PtdEtOH and diacylglycerol formation from exogenous PtdCho. It is proposed that unsaturated fatty acids may play a physiological role in the regulation of diacylglycerol production through activation of phospholipase D and phosphatidate phosphohydrolase. PMID- 1459144 TI - Chromatin structure and conserved sequence elements in genes encoding ribosomal proteins in Tetrahymena thermophila. AB - The chromatin structure of the macronuclear genes encoding ribosomal proteins S25 and L1 in the ciliated protozoan Tetrahymena thermophila was analyzed. Using the indirect end-labelling technique, DNase-I-hypersensitive regions were located in the promoter regions as well as in the 3' regions of the genes. The DNase-I hypersensitive regions were present in chromatin of exponentially growing cells, where the rate of ribosomal-protein gene transcription is high, and in chromatin from starved cells, where transcription of ribosomal-protein genes is severely depressed. Micrococcalnuclease-digestion experiments revealed that the promoter regions of the S25 gene and the L1 gene are devoid of nucleosomes in exponentially growing cells. In starved cells, no nucleosomal organisation of the promoter region of the L1 gene could be detected, whereas nucleosomal structures were discernible in the promoter region of the S25 gene. A conspicuous polypurine sequence motif, AARGGGAAA, is present within or adjacent to the DNase-I hypersensitive regions in the promoter of the S25 and the L1 gene, and interestingly, the same motif is found also in the promoter regions of the genes encoding ribosomal proteins L21 and L37. PMID- 1459143 TI - Studies on the interaction of alpha subunits of GTP-binding proteins with beta gamma dimers. AB - The interaction of several preparations of purified beta gamma dimers with two types of guanosine-nucleotide-binding-regulatory-(G)-protein alpha subunits, a recombinant bv alpha i3, made in Sf9 Spodoptera frugiperda cells by the baculovirus (bv) expression system, and alpha s, either purified from human erythrocyte Gs-type GTP-binding protein, and activated by NaF/AlCl3, or unpurified as found in a natural membrane, were studied. The beta gamma dimers used were from bovine rod outer segments (ROS), bovine brain, human erythrocytes (hRBC) and human placenta and contained distinct ratios of beta subunits that, upon electrophoresis, migrated as two bands with approximate M(r) of 35,000 and 36,000, as well as distinct complements of at least two gamma subunits each. When tested for their ability to recombine at submaximal concentrations with bv alpha i3, ROS, brain, hRBC and placental beta gamma dimers exhibited apparent affinities that were the same within a factor of two. When bovine brain, placental and ROS beta gamma dimers were tested for their ability to promote deactivation of Gs, brain and placental beta gamma dimers were equipotent and at least 10-fold more potent than that of ROS beta gamma dimers; likewise, brain beta gamma and placental dimers were equipotent in inhibiting GTP-activated and GTP-plus-isoproterenol-activated adenylyl cyclase, while ROS beta gamma dimers were less potent when assayed at the same concentration. The possibility that different alpha subunits may distinguish subsets of beta gamma dimers from a single cell was investigated by analyzing the beta gamma composition of three G proteins, Gs, Gi2 and Gi3, purified to near homogeneity from a single cell type, the human erythrocyte. No evidence for an alpha-subunit-specific difference in beta gamma composition was found. These findings suggests that, in most cells, alpha subunits interact indistinctly with a common pool of beta gamma dimers. However, since at least one beta gamma preparation (ROS) showed unique behavior, it is clear that there may be mechanisms by which some combinations of beta gamma dimers may exhibit selectivity for the alpha subunits they interact with. PMID- 1459145 TI - Evidence for two histidine ligands at the diiron site of methane monooxygenase. AB - Circular dichroism spectroscopy has shown the hydroxylase component of methane monooxygenase to have a high helical content. The apoprotein has the same secondary structure as the holoenzyme. Chemical modification shows 12 histidines to be reactive with diethylpyrocarbonate in the holoenzyme, whereas 14 are reactive in the apoenzyme. Two histidine residues are implicated as iron ligands. Further chemical modification results suggest a cysteine residue is in close proximity to the diiron centre. PMID- 1459146 TI - The kinetic mechanism of sheep liver sorbitol dehydrogenase. AB - The relations between the kinetic parameters for both sorbitol oxidation and fructose reduction by sheep liver sorbitol dehydrogenase show that a Theorell Chance compulsory order mechanism operates from pH 7.4 to 9.9. This is supported by many parallels with the kinetics of horse liver alcohol dehydrogenase, which operates by this classical mechanism. An isotope-exchange study using D (2H8)sorbitol confirmed the existence of ternary complexes and that, under maximum velocity conditions, their interconversion is not rate-determining. Substrate inhibition at high concentrations of D-sorbitol or D-fructose confirmed rate-determining enzyme--coenzyme product dissociation, slowed by the existence of more stable abortive ternary enzyme-coenzyme product complexes with substrate. The effect of the inhibitor/activator 2,2,2-tribromoethanol showed the existence of enzyme-NAD-CBr3CH2OH complexes inhibiting the first phase of reaction and enzyme-NADH-CBr3CH2OH complexes dissociating more rapidly than the usual rate determining enzyme-NADH coenzyme product dissociation in the final phase. Inhibition studies with dithiothreitol also confirmed an ordered binding of coenzymes and second substrates to sorbitol dehydrogenase. Neither D-sorbitol nor D-fructose had any effect on enzyme inactivation by the affinity labelling reagent DL-2-bromo-3-(5-imidazolyl)propionic acid, thus giving no evidence for their existence as binary enzyme-substrate complexes. Several alternative polyol substrates for sorbitol dehydrogenase gave the same maximum velocity as sorbitol. This indicated a common rate-limiting binary enzyme-NADH product dissociation and a similarity of mechanism. An enzyme assay for pH 7.0 and 9.9 is given which enables the concentration of sorbitol dehydrogenase to be determined from initial rate measurements of enzyme activity. PMID- 1459147 TI - Radical prostatectomy in the management of stage A carcinoma of the prostate. AB - A total of 115 patients (29 with stage A1 and 86 with stage A2 prostate cancer) underwent radical retropubic prostatectomy. Residual cancer was found in the radical prostatectomy specimens in 11 of the 29 stage A1 patients (38%) and in 66 of the 86 stage A2 patients (77%). Fourteen percent of the stage A1 patients and 29.5% of the stage A2 patients had pathological evidence of disease extension beyond the confined prostate. No perioperative death occurred and no patient suffered rectal injury or was totally incontinent. Early postoperative complications occurred in 6 patients (5%). There were no late complications. Complete urinary control was achieved in 111 patients (96.5%) and stress urinary incontinence was present in 4 patients (3.5%). Sexual function was preserved in 21 of the 26 patients (81%) who underwent a nerve-sparing radical prostatectomy. Follow-up ranged from 12 to 84 months with a mean of 30 months. All patients were alive at the time of this study and only 3 patients suffered disease progression. These 3 patients were among the stage A2 group and had pathological evidence of tumor extension beyond the prostatic capsule. Twenty-six patients who also had evidence of disease extension were alive without evidence of disease. These data demonstrate that patients with stage A disease are at risk for disease progression if left untreated and with a morbidity as low as that achieved in our series, radical prostatectomy should remain an optimal option for tumor control in these patients. PMID- 1459148 TI - Buserelin treatment of advanced prostatic carcinoma: prognostic factor analysis. AB - From August 1986 to August 1990, 116 patients with prostatic carcinoma, advanced disease (stage C-D1 only in patients older than 75 years, or D2) were treated with Buserelin (0.5 mg 3 times/day subcutaneously for 7 days, followed by 0.4 mg 3 times/day intranasally) until progression. No concomitant antiandrogens were administered. Of the 108 evaluable patients, 10 had complete remission (CR), 49 partial remission (PR), 46 remained stable while 3 progressed (response rate = 54.6%). Median duration of response was 31 months, median survival was 34 months. The toxicity of treatment was mild and mainly related to the hormonal effect of the drug. Castrate testosterone levels were obtained in all patients except 7. Slight, transient pain increase was noted at day 8 in 12 patients. Absence of symptoms at the start of treatment, well- or moderately differentiated tumor and serum testosterone negativization following Buserelin were associated with a significantly higher response rate as compared to presence of symptoms, poorly differentiated tumor and failure to obtain castrate testosterone levels, respectively. The following prognostic factors were found, at univariate analysis, to be associated with a prolonged survival: stage (C-D1 versus D2), PS (greater than 80 versus equal or less than 80), symptoms (absent versus present) and histological grade (G1 + G2 versus G3). Age and basal T levels did not influence survival. Those patients who obtained a CR or PR survived significantly longer than those with stable disease or progression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459149 TI - Value of electrical dispersion as a cause of urethral stenosis after endoscopic surgery. AB - We have evaluated the incidence of iatrogenic urethral strictures in a prospective study of 125 patients with a diagnosis of initial, superficial bladder tumors (without prior urethral instrumentation) and who were treated with endoscopic surgery. A global incidence of 12% was found after 24 months of follow up with the strictures detected a mean of 9.5 months after the endoscopic procedure. These patients were divided into two groups. Group 1 was treated using standard transurethral resection (TUR) and group 2 underwent Nd:YAG laser photocoagulation. Both populations of patients underwent cystoscopic controls every 4 months as part of our standard follow-up protocol in bladder tumors. In the group of patients who underwent diathermy using a 24-F sheath (85 patients), the percentage of stenosis was 16.4%. In the patients treated with laser via a 21 F panendoscope (40 patients), the incidence of postoperative urethral stenosis was only 2.5%. We believe that the electrical dispersion generated by the unipolar electric current as well as the caliber of the operating instruments are factors which may influence the development of iatrogenic endoscopic urethral strictures. PMID- 1459150 TI - Clinical study of the longitudinal deformation of the flaccid penis and of its variations with aging. AB - The length changes of the flaccid penis provoked by a maximum manual stretching of the glans have been measured in 905 men in order to study its biomechanical qualities. Our study shows that the flaccid penis is deformable, extensible and elastic in its longitudinal axis. The analysis of the variations of these biomechanical properties with aging shows a significant decrease. Thus, the biomechanical behavior of the flaccid penis during stretching is highly different in young men and old men. This distortion difference according to age proves the physiological importance of the penile distortion since impotence significantly increases with age. As the vascular mechanisms may be disregarded during flaccidity, these penile physical features of the flaccid penis are only due to tissue mechanisms. Consequently, any distortion loss would reflect a tissue impairment, very likely a progressive senile fibrosis of cavernous tissues. PMID- 1459151 TI - Incidentally diagnosed renal cell carcinoma. AB - We analyzed the incidence, sex and age distribution, diagnostic methods and survival rate of incidentally detected renal cell carcinomas (RCCs) and compared these factors with those of symptomatic RCCs. Of 141 patients with RCC treated between 1980 and 1989, 44 cases (31.4%) were incidentally detected. Thirty-one of these 44 cases were diagnosed by abdominal ultrasonography. The age of the incidental cases was significantly higher than that of the symptomatic ones (p = 0.045), particularly in male patients (p = 0.049). The tumor size in incidental cases was smaller and tumor stage earlier (p less than 0.0001). Moreover, the grade of malignancy was significantly lower, and clear cell type tumors were more frequently detected in the incidental cases. No difference was observed between the survival rates of incidental and symptomatic cases with stage 1 or 2 tumors. Of the incidental cases with stage 1 or 2, however, no patient with a tumor 3 cm or less in diameter has died. In conclusion, abdominal ultrasonography is a useful tool to detect RCC at an early stage, and patients with a relatively small tumor tend to have a good prognosis. PMID- 1459152 TI - Studies of temperature rise in bladder cancer and surrounding tissues during radiofrequency hyperthermia. AB - Temperatures in the tumor on the bladder wall, tumor margin, intravesical urine, rectal cavity and pubic subcutaneous fat tissue (SCFT) were measured in a total of 48 bladder tumor patients during radiofrequency (RF)-capacitive heating of the tumors. There were close correlations (p less than 0.01) between the temperature of the tumor margin and intratumor temperature, between the intravesical temperature and the temperature of the tumor margin, between the RF power applied and the intravesical temperature and also between the thickness and the temperature of SCFT. As long as the thickness of SCFT was 20 mm or less, it was possible to raise the temperature of bladder cancer to 42.5 degrees C or above. The intravesical temperature could be regarded as an indicator for hyperthermia treatment since the intravesical urine temperature of over 42 degrees C implied a therapeutic temperature of 42.5 degrees C or more in the margin of the tumor. Since the intravesical temperature was closely related to the output power, the therapeutic magnitude of the output power could be defined at least as 400 W, by which intravesical urine temperature could exceed 42 degrees C. PMID- 1459153 TI - Immunophenotypic characterization of the bladder mucosa infiltrating lymphocytes after intravesical BCG treatment for superficial bladder carcinoma. AB - The lymphocytes infiltrating the bladder mucosa of 28 patients treated with bacillus Calmette-Guerin (BCG) for superficial bladder carcinoma were characterized using an immunohistochemical technique on frozen sections of biopsy specimens obtained during cystoscopy. The inflammatory response induced by BCG consisted mainly of T lymphocytes (CD3+), most of which had the helper/inducer phenotype (CD4+), with a CD4/CD8 ratio greater than 1. A minor subset of lymphocytes were of B phenotype (CD22+). These findings persisted for the whole follow-up period (6-12 months) in spite of a progressive decrease of the inflammatory infiltrate. No difference in the lymphocyte phenotype was observed between nonresponding patients and those who responded to BCG in the short term. It is concluded that, although intravesical BCG therapy does affect the immunocompetent cells of the bladder wall, the BCG-induced antitumor activity is unlikely to depend exclusively on a local immune mechanism. PMID- 1459154 TI - Postoperative long-term course of peripheral blood immune parameters and immunomodulating effects of keyhole limpet hemocyanin in patients with nonmetastatic renal cell carcinoma. AB - Therapeutic approaches to metastatic renal cell carcinoma (RCC) often focus on the application of immune modulators; the success rates, however, are not satisfactory. Up to the time of this study, no diagnostic tool has been available to select those patients who might profit from immunotherapy. Starting from this point, we have been assessing the immune status of patients suffering from RCC, intending to find markers that would characterize the more favorable prognosis. Our interest is focused not only on the metastatic but also on the nonmetastatic disease, i.e., the disease with the better prognosis. In the present study, we have assessed both the postoperative long-term course of several immune parameters of the peripheral blood and the reactivity of the immune system to immunostimulation with keyhole limpet hemocyanin (KLH) in patients with nonmetastatic RCC. In a prospectively randomized study, the verum group (n = 8) got 1 mg KLH per month up to 1 year while the control group (n = 9) got no immunostimulator after tumor nephrectomy. Both patient groups had stable or even increasing cell counts of lymphocyte subpopulations (T, B, natural killer, T4, T8 cells), and the humoral immunoactivation markers neopterin, beta 2-microglobulin and tumor necrosis factor increased considerably after tumor nephrectomy. An effect of KLH is evident 4-8 months postoperatively: here, the neopterin values in the KLH group are more than twice as high as in the control group. Thus, while patients with metastatic disease had turned out to be immunosuppressed (previous study), in patients with nonmetastatic RCC, both the long-term course indicating postoperative immunostimulation and the reactivity to KLH give evidence of immunocompetence. PMID- 1459155 TI - Renal insufficiency induced by parathyroid hormone: influence of the calcium antagonist Go 6070. AB - To study the pathogenesis of parathyroid-hormone-induced renal insufficiency and the influence of the new calcium channel antagonist Go 6070 (Godecke AG, Berlin, FRG) rats were assigned to three groups (n = 8 each): (1) control, (2) PTH, (3) PTH plus Go 6070. PTH (30 micrograms/24 h, a nonhypercalcemic dose) was administered i.p. and Go 6070 (1 mg/kg/24 h) p.o. for 6 days. PTH did not change plasma or urinary calcium and did not induce nephrocalcinosis. The glomerular filtration rate (GFR), however, was decreased (4.9 vs. 10.3 ml/min/kg). Concomitant administration of Go 6070 attenuated the PTH-induced fall in GFR (6.2 ml/min/kg). PMID- 1459156 TI - Role of the autonomic nervous system in catheter-induced urethral inflammation. AB - We have studied role of the autonomic nervous system on experimentally induced urethral inflammation in the rat. Urethral inflammation was produced by inserting latex strips into the urethra. The effects of different experimental procedures were assessed by using a 4-grade inflammation scale based on histological findings. Rats pretreated with the nonspecific catecholamine depletors reserpine or quanethidine had a significantly less severe urethral inflammation than vehicle-treated controls. The severity of urethral inflammation was increased in spontaneous hypertensive rats, which have an increased sympathetic tone as compared to the normotensive rats. Propranolol, a nonselective beta-adrenergic receptor antagonist reduced and butoxamine, a beta 2-antagonist, significantly reduced the urethral inflammation. Neither phenoxybenzamine (nonselective) nor prazosin (alpha 1) or yohimbine (alpha 2), alpha-adrenergic receptor antagonists, affected the degree of urethral inflammation. These data taken together indicate that the autonomic innervation of the urethral mucosa is critically involved in the inflammatory reaction and that the use of beta 2-antagonist may be a treatment alternative in the future for the treatment of catheter-induced inflammation. PMID- 1459157 TI - Blind-ending bifid ureters--report of five pediatric cases. AB - We report 5 cases of blind-ending ureters according to Culp's criteria. Occurrence of vesicoureteral reflux allowed us to make the diagnosis of retrograde cystography in all our patients. We wish to emphasize that this procedure must be done as the first step of urinary tract examination in children. PMID- 1459158 TI - Polyorchidism: an exceptional case of three homolateral testes. AB - Polyorchidism is an uncommon congenital anomaly defined as the presence of more than two histologically proved testes. The present case of polyorchidism was discovered casually in an 11-year-old boy while performing an orchiopexy. Three testes were found on the left side; we have been unable to find this exceptional anomaly previously published in the medical literature. PMID- 1459159 TI - Intrascrotal extratesticular malignant schwannoma. AB - We report a rare case of intrascrotal extratesticular malignant schwannoma with rhabdomyoblastic features in a 48-year-old man. Malignant schwannomas, which arise from the peripheral nerves, usually occur in the extremities, the trunk or paravertebral areas. The patient had no manifestation of von Recklinghausen's disease. To our knowledge, there has been no intrascrotal extratesticular malignant schwannoma reported. PMID- 1459160 TI - A practical and theoretical guide to measurement invariance in aging research. AB - We describe mathematical and statistical models for factor invariance. We demonstrate that factor invariance is a condition of measurement invariance. In any study of change (as over age) measurement invariance is necessary for valid inference and interpretation. Two important forms of factorial invariance are distinguished: "configural" and "metric". Tests for factorial invariance and the range of tests from strong to weak are illustrated with multiple group factor and structural equation modeling analyses (with programs such as LISREL, COSAN, and RAM). The tests are for models of the organization and age changes of intellectual abilities. The models are derived from current theory of fluid (Gf) and crystallized (Gc) abilities. The models are made manifest with measurements of the WAIS-R in the standardization sample. Although this is a methodological paper, the key issues and major principles and conclusions are presented in basic English, devoid of technical details and obscure notation. Conceptual principles of multivariate methods of data analysis are presented in terms of substantive issues of importance for the science of the psychology of aging. PMID- 1459161 TI - Modeling incomplete longitudinal and cross-sectional data using latent growth structural models. AB - In this paper we describe some mathematical and statistical models for identifying and dealing with changes over age. We concentrate specifically on the use of a latent growth structural equation model approach to deal with issues of: (1) latent growth models of change, (2) differences in longitudinal and cross sectional results, and (3) differences due to longitudinal attrition. This is a methodological paper using simulated data, but we base our models on practical and conceptual principles of modeling change in developmental psychology. Our results illustrate both benefits and limitations using structural models to analyze incomplete longitudinal data. PMID- 1459162 TI - Types of change: application of configural frequency analysis in repeated measurement designs. AB - Many researchers are concerned both with intraindividual change patterns and interindividual differences and similarities in those change patterns. Configural Frequency Analysis (CFA) provides a way to identify overrepresentations (types) and underrepresentations (antitypes) in the frequencies of multiple variable classifications organized to reflect patterns of change. Three methods of CFA for analyzing repeated measures data are considered. To establish trends, two of them require at least ordinal data and the third requires interval data. Data analysis and the interpretation of results are illustrated. CFA is compared with residual analysis from log-linear modeling. PMID- 1459163 TI - Multitrait-multimethod models in aging research. AB - The multitrait-multimethod matrix is a versatile tool for structuring the design and analysis of studies in many areas of psychology, including the aging of psychological processes. The basic goal for which the multitrait-multimethod matrix was developed is the establishment of the construct validity of measures. With newer forms of analyzing multitrait-multimethod data, particularly those using structural equation modeling, it is possible to specify models and employ model comparisons for an even broader goal: the more adequate generalization of conclusions across the facets included in the study. Topics addressed in this paper include the design of multitrait-multimethod studies, the specification of an array of structural models for such data, model comparisons that allow the estimation of the degree of convergent validity, discriminant validity, and method variance exhibited by a set of measures, and the extension of structural models to more than a single group, which allows the testing of questions regarding means, as well as the traditional tests of differences in variance and covariance. The procedures discussed are then explicated by describing the representation of data from a hypothetical four-group study of memory employing a form of design that is common in research on aging. Strengths and weaknesses of the structural modeling approach to the analysis of multitrait-multimethod data are discussed. PMID- 1459164 TI - Component analysis in multivariate aging research. AB - A method of components analysis, related to principal components analysis, is described for applications in multivariate cross-sectional or longitudinal data. The method may be useful to researchers seeking to reduce the number of observed variables through scale construction. The method creates component variables as weighted sums of the observed variables using weights that are identical across groups and occasions. The statistical and conceptual properties of these components are discussed. The method is contrasted with traditional principal components analysis and factor analysis. An application of the method is presented using longitudinal WAIS and WAIS-R data. PMID- 1459165 TI - Age, cohort, and time development muddles: easy in practice, hard in theory. AB - The debate among developmental psychologists over how best to combine longitudinal and cross-sectional data sequences can be traced back at least four decades. During the 1970s, a variation of this theme received much attention: could the developmental influences of age, cohort, and time be unraveled by sufficiently ingenious application of combined data sequences? We believe discussion of this question has been needlessly parochial and confused. Substantive and methodological contributions from other disciplines have, until recently, been largely ignored by developmental psychologists. Moreover, the solutions debated by psychologists have generally been formulated in language that obscured, rather than explicated, the formal indeterminacy implicit in models of age, cohort, and time parameters. Methodologists have outlined formal solutions to problems of indeterminacy in the contexts of model identification and estimability theory. Sociologists have proposed solutions, based on explicitly theoretical assumptions, that permit model identification and unambiguous interpretation. We review these contributions, and suggest a hierarchy of solutions to the problem of age, cohort, and time indeterminacy. PMID- 1459166 TI - Age-based construct validation using structural equation modeling. AB - In this paper we describe some mathematical and statistical models based on structural equation modeling (SEM) using computer programs like LISREL. We focus on SEM methodology for the simultaneous examination of the internal validity of psychological constructs and the external validity represented by age relations. To illustrate these ideas we use a latent variable path model to examine the organization of intellectual abilities measured by the WAIS-R in the standardization sample. We also examine different ways in which age can be used to structure this organization. This is primarily a methodological paper, but we try to integrate conceptual principles of modeling with some substantive issues of research on the psychology of aging. PMID- 1459167 TI - Abnormal neuroendocrine immune communications in patients with rheumatoid arthritis. PMID- 1459168 TI - Increased tissue concentrations of the gastrin precursor in patients treated with omeprazole. AB - The main form of gastrin in antral mucosa, the amidated heptadecapeptide G17, is generated from an inactive precursor, progastrin, by steps involving endopeptidase cleavage and amidation. Gastrin cells are normally inhibited by gastric acid and in this study we have examined how suppression of acid by treatment with omeprazole for 6-8 weeks influences gastrin production in patients with oesophagitis. Plasma concentrations of total amidated gastrins in the fasting state increased from 18 to 43 pmol l-1; assays specific for G17 immunoreactivity indicated that the plasma concentrations of this form increased from 6 to 12 pmol l-1. In endoscopic biopsies of antral mucosa there was no change with omeprazole treatment in the concentrations of total amidated gastrins, or their immediate precursors, the Gly-extended gastrins. However, assays using an antibody that reacts with progastrin, together with size exclusion chromatography, indicated that tissue progastrin concentration increased 6-fold. The data suggest a modest net increase in gastrin production with omeprazole-treatment; because the ratio of tissue concentrations of total amidated gastrins to Gly-extended gastrins did not change, it would seem that the amidating capacity of the gastrin cell was maintained. However, the increase in progastrin concentrations suggests a relative failure of the initial steps of post-translational processing, and consequently that in certain circumstances endopeptidase cleavage of progastrin may be rate limiting. PMID- 1459169 TI - Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus. AB - The effects of dietary supplementation with n-3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. The serum triglyceride (TG) concentrations decreased by 27% (P < 0.01) after addition of MaxEPA with a reduction of VLDL TG by 36% (P < 0.05) while LDL cholesterol increased by 6% (P = 0.05). The fasting blood sugar and HbA1c concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period. The highest glucose concentrations at fasting and after an i.v. glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged. The peripheral insulin sensitivity, as measured by a euglycaemic, hyperinsulinaemic clamp technique, did not change during the study. The mean plasminogen inhibitor 1 (PAI-1) activity of the patients was elevated compared with healthy controls. In spite of the reduction of the triglyceride concentrations and unchanged insulin levels, there was a significant increase of the activity of PAI-1 (+21%, P < 0.01) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity. In many situations there seems to be a reduction of PAI-1 when the triglycerides are lowered. In the diabetic patients given n-3 fatty acids this was not the case. PMID- 1459170 TI - In vitro immune modulation of polymorphonuclear leukocyte adhesiveness by sodium fluoride. AB - We investigated the influence of sodium fluoride on polymorphonuclear leukocyte (PMN) adhesiveness in a healthy subject with low serum levels of fluoride. The PMN were separated from venous blood, and the percentages of adhered and unadhered cells were determined in vitro in plastic culture plates. The cells were cultured with five different fluoride concentrations ranging from 6.25 10( 2) microM to 4.0 microM in the presence and absence of autologous serum. PMN adhesiveness in both the presence and in the absence of autologous serum was 98.5%; the addition of fluoride had no effect on the results in the absence of serum. However, in the presence of autologous serum, PMN adhesiveness decreased significantly with the addition of fluoride (P < 0.05) from 0.5 microM. The decrease was smaller (1.1%) at a concentration of 0.125 microM, and larger at 12 times this concentration of fluoride (52.7%). We conclude that sodium fluoride reduces PMN adhesiveness in a dose-dependent manner. The effect is not direct, but should be modulated by a seric factor. PMID- 1459171 TI - Antibody mediated enhancement of HIV-1 infection of an EBV transformed B cell line is CD4 dependent. AB - Low levels of anti-viral antibodies may facilitate virus infection of Fc-receptor bearing cells. For human immunodeficiency virus (HIV) it has been reported that antibodies can enhance infection of phagocytic cells. We show that HIV-1 can infect an Epstein-Barr virus transformed B cell line and that low levels of anti HIV antibodies enhance infection. The enhanced infection was characterized by an increase in viral DNA and increased HIV p24 protein production. Detection of cell surface antigen expression of CD4, the receptor for HIV, Fc-receptor type II for IgG, but not of type I and III could be demonstrated by immunofluorescence cytometry. The enhancement was abrogated when infection was performed in presence of a monoclonal antibody directed against CD4. Based on these results we conclude that antibody mediated enhancement of HIV-1 infection can also occur in non phagocytic cells in a CD4 dependent manner and that IgG Fc-receptors other than types I or III are involved in this process. PMID- 1459172 TI - Circulating inhibitor of interleukin 1 activity in patients with chronic renal diseases. AB - The effects of sera derived from patients suffering from chronic renal diseases (endemic Balkan nephropathy, glomerulonephritis and pyelonephritis) on T cell proliferative response was studied. It was found that these sera contained factors which affect interleukin 1 (IL-1) dependent events in T cell proliferative response. The factors prevent costimulatory effects of IL-1 on T cells but do not bind to IL-1, nor do they affect interleukin 2 (IL-2) dependent T cell proliferation. These findings indicate that immuno-suppression observed in some kidney disorders may be partially due to serum immunoinhibitory factors affecting IL-1 activity. PMID- 1459174 TI - The critical role of magnesium ions in osteoclast-matrix interaction: implications for divalent cations in the study of osteoclastic adhesion molecules and bone resorption. PMID- 1459173 TI - The effects of dietary supplementation with n-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial. AB - STUDY OBJECTIVE: To determine the effect of dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) on disease variables in patients with rheumatoid arthritis. DESIGN: Multicenter, randomized, placebo controlled, double blind. SETTING: Three Danish hospital Departments of Rheumatology. PATIENTS: Fifty-one patients with active rheumatoid arthritis. INTERVENTION: Random allocation to 12 weeks of treatment with either six n-3 PUFA capsules (3.6 g) or six capsules with fat composition as the average Danish diet. MAIN RESULTS: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. CONCLUSIONS: Dietary supplementation with n-3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n-3 PUFA in the treatment of rheumatoid arthritis. PMID- 1459175 TI - Insulin sensitivity and secretion in healthy elderly human subjects with 'abnormal' glucose tolerance. AB - Glucose tolerance deteriorates dramatically with advancing age. It is not known whether the underlying pathophysiology is different in older subjects. We employed a two step hyperinsulinaemic euglycaemic glucose clamp with [6(14)C] glucose infusion to compare peripheral and hepatic insulin sensitivity in eight elderly (EAGT) with eight young (YAGT) subjects with abnormal (matched) glucose tolerance and nine elderly subjects with normal glucose tolerance (ENGT). There was no difference in basal HGO (EAGT 14.5 +/- 0.9, YAGT 15.3 +/- 1.1 mumol kg-1 min-1). Glucose turnover was similar in both groups at step 1 (EAGT 13.2 +/- 0.8, YAGT 13.4 +/- 0.8 mumol kg-1 min-1) and step 2 (EAGT 25.1 +/- 3.1, YAGT 27.2 +/- 2.7 mumol kg-1 min-1). HGO was lower in the EAGT subjects at step 1 (2.3 +/- 0.4 vs. 4.3 +/- 0.6 mumol kg-1 min-1 P = 0.01). Incremental serum insulin response to oral glucose was comparable (EAGT 66.8 +/- 11.6 YAGT 57.8 +/- 12.2 mU l-1.h). Compared to the ENGT group the EAGT group was insulin resistant with a lower MCR of glucose at step 1 (2.03 +/- 0.28 vs. 3.23 +/- 0.44 ml kg-1 min-1 P = 0.04) and at step 2 (6.18 +/- 0.83 vs. 9.64 +/- 0.38 ml kg-1 min-1 P = 0.004) and had a lower early insulin response (AUC 0-30 min 5.9 +/- 1.1 vs. 9.8 +/- 1.4 mU l-1.h P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459176 TI - Increased GPIIB/IIIA expression and altered DNA-ploidy pattern in megakaryocytes of diabetic BB-rats. AB - Hyperactive platelets contribute to angiopathic complications in diabetes mellitus. It is unclear whether the increased platelet function is a primary pathogenetic factor in diabetes or follows vascular injury. Increased platelet size and numbers of glycoprotein receptors on diabetic platelets suggest that thrombopoiesis is altered in diabetes mellitus. For further support of this hypothesis we studied whether megakaryocytes are changed with regard to the DNA ploidy pattern and the GPIIB/IIIA expression in 10 acute diabetic (AD) and 24 insulin treated diabetic (ITD) BB rats in comparison with 22 diabetes resistant (ND) BB rats. In the AD group megakaryocyte size (P = 0.035) and the modal DNA ploidy distribution dropped (P = 0.0001) concomitant with increased TNF-alpha activity (P = 0.001). GPIIB/IIIA expression and the peripheral platelet status were unchanged. After 4 weeks of insulin substitution metabolic parameters (glucose, cholesterol, triglycerides) were lowered, but remained still elevated. As compared to the AD group the modal DNA-ploidy pattern reversed, but the relative percentage of 64n megakaryocytes increased 2.3-fold and GPIIB/IIIA expression increased 1.6-fold. Simultaneously, the peripheral platelet count and size increased. From these results we conclude that alterations of the megakaryocyte compartment occur at early onset of diabetes. These changes could reflect a response to increased systemic cytokine production during inflammatory islet cell destruction. The peripheral platelet thrombotic potency increased with insulin treatment. This was associated with an increase of 64n-megakaryocytes with upregulated GPIIB/IIIA expression and could reflect a mitogenic effect of insulin upon the endomitotic cycle of the megakaryocytes. PMID- 1459177 TI - Correspondence between plasma mevalonic acid levels and deuterium uptake in measuring human cholesterol synthesis. AB - To assess the validity of two techniques capable of identifying immediate changes in human cholesterol production, plasma mevalonic acid levels and the rate of uptake of deuterium into plasma free cholesterol were compared in 5 healthy individuals over 48 h. The free-living subjects self-selected three meals per day prior to and during study. At t = 0, deuterium oxide was administered orally. Blood samples were collected before and every 4 h after dosing. Total cholesterol and mevalonic acid levels were determined in plasma at each timepoint. Deuterium enrichment changes in plasma free cholesterol, relative to plasma water content, were used to calculate free cholesterol fractional synthetic rates (FSR) at each timepoint. Total plasma cholesterol levels remained constant, whereas significant circadian rhythmicity was observed in both plasma mevalonic acid and deuterium uptake methods, with nadir and peak formation rates indicated at 14.00 to 16.00 h and about midnight, respectively. It is suggested that plasma mevalonic acid levels and free cholesterol deuterium uptake rate techniques are both suitable techniques for short-term measurement of human cholesterol synthesis. PMID- 1459178 TI - Effect of lipid A on the deformability, membrane rigidity and geometry of human adult red blood cells. AB - Lipid A is responsible for the activities of endotoxin and may cause circulatory failure and haemolysis. This study evaluated the effects of different lipid A concentrations on red blood cell (RBC) deformation (rheoscope), the aspiration pressure required to aspirate RBC into 3.3 microns pipettes, the membrane shear elastic modulus (i.e. membrane rigidity) and cellular geometry (micropipette system) after 15 min of incubation. Lipid A concentrations of 10 and 100 micrograms ml-1 of RBCs decreased RBC deformability by 26% and 39%, respectively. The aspiration pressure for RBCs into a 3.3 microns micropipette increased by 235% at a lipid A concentration of 10 micrograms ml-1 and by 586% at a concentration of 100 micrograms ml-1. The elastic shear modulus almost doubled at a lipid A concentration of 10 micrograms ml-1 and tripled at 100 micrograms ml-1. At a lipid A concentration of 100 micrograms ml-1, 37% of RBCs showed spicules. These echinocytes were less deformable than discocytes. Mean corpuscular volume, RBC volume and surface area were not affected by lipid A. We conclude that lipid A causes marked reduction of RBC deformability due to increasing membrane rigidity. PMID- 1459179 TI - Colchicine analogues: effect on amyloidogenesis in a murine model and, in vitro, on polymorphonuclear leukocytes. AB - Colchicine has been used in diverse clinical settings such as gout, familial Mediterranean fever, liver cirrhosis, Behcet's disease and pericarditis. It also has an antimitotic potential hitherto unexplored due to its narrow therapeutic toxic ratio. The aim of the present study was to compare the effectiveness and the toxicity of colchicine and three analogues: thiocolchicine, 2,3 dimethyl colchicine and 3-dimethylthiocolchicine in the blockage of amyloid synthesis in a murine model. 3-demethylthiocolchicine was equipotent to colchicine in the blockage of casein induced amyloidogenesis. However, it was markedly less toxic (LD50 11.3 mg kg-1 vs. 1.6 mg kg-1). Thiocolchicine was toxic (LD50 1.0 mg kg-1) and 2,3 didemethyl-colchicine was far less effective. The effect of 3 dimethylthiocolchicine on polymorphonuclear leukocytes was then compared to colchicine. The effect of this analogue on inhibition of chemotaxis was equivalent to that of colchicine whereas the latter was superior to the analogue in the suppression of phagocytosis (by a ratio of 2:1) and in the inhibition of bactericidal activity (by a ratio of 10:1). Since in therapeutic concentrations the only detectable effect of colchicine on PMNs is inhibition of chemotaxis, our data may point to 3-demethylthiocolchicine as an optional, perhaps superior alternative to colchicine for some of its therapeutic indications. PMID- 1459180 TI - Neuropsychological impairment in auto-immune disease. AB - Estimations of the prevalence of central nervous system involvement in patients with systemic lupus erythematosus (SLE) vary from 25 to 75%. In order to assess possible deficits in memory, attention, and/or reaction time, a battery of neuropsychological tests was administered to 15 patients with SLE and to two matched groups of control subjects; eight patients on corticosteroids and 15 healthy controls. The test battery included the Multiple Choice Word Fluency Test (MWT-B), Benton Visual Memory Scale, Syndrome Short Test (SKT; attention and memory), Attention and Concentration Test (d2), Wechsler Adult Intelligence Scale (WAIS) subtests for Comprehension, Digit Span, Block Design, a Computer Controlled Reaction Time task (CCRT), and a Learning and Memory Test (LGT-3). Results revealed a statistically significant short-term memory deficit (for all six relevant subtests used) and a marked delayed simple reaction time in SLE patients as compared with scores in healthy subjects. An attention deficit as well as the expected difference between the estimated premorbid and actual level of intelligence could not be demonstrated. With three exceptions (SKT-9 figural recognition, Benton Visual Memory, and LGT-3 figural recognition), patients treated with corticosteroids did not differ from healthy controls. They also did not differ from SLE patients in any of the parameters tested. It therefore appears that the demonstrated deficit in short-term memory and reaction time in SLE patients may not only be due to the neuropsychiatric manifestation of SLE but possibly also result from medication side-effects. PMID- 1459181 TI - Neuroimmunological axis and rheumatic diseases. PMID- 1459182 TI - Modulation of the immune response to stress in patients with systemic lupus erythematosus: review of recent studies. AB - Physical and psychological stress in healthy subjects leads to characteristic alterations of plasma hormone concentrations and the lymphocyte subset distribution. After short-term bicycle ergometry or acoustic stress, and after a 2-h-long neuropsychological examination, a rise in B- and T-suppressor/cytotoxic lymphocytes and a decrease in T-helper lymphocytes has been shown to occur. This cell mobilization was accompanied by an elevation in plasma catecholamines. Although the rise in catecholamine levels was similar in patients with systemic lupus erythematosus (SLE) and in healthy subjects, the alterations in the lymphocyte subsets were less pronounced in SLE patients after bicycle ergometry as well as after psychological testing than in healthy subjects, patients with sarcoidosis, and patients without collagenosis under treatment with corticosteroids. Differences between short-term physical exercise and the acoustic stress test on the one hand, and the 2-h-long neuropsychological test on the other, were observed only for the absolute lymphocyte count. After short-term stress, a rise in the leukocyte and lymphocyte count was noted, whereas after long-term testing, only an increase in leukocytes and a decrease in lymphocytes could be found. In conclusion, sympathomimetic stimulation by bicycle ergometry or by psychological stress led to a characteristic cell mobilization in all the groups investigated. The extent of cell mobilization was attenuated in SLE patients despite the fact that comparable increases of plasma catecholamines were observed. PMID- 1459183 TI - Modulation of lymphocyte subsets due to psychological stress in patients with rheumatoid arthritis. AB - The influence of a 1-hour neuropsychological stress test on the distribution of lymphocyte subpopulations and on plasma catecholamine levels was investigated in 18 patients with rheumatoid arthritis (RA) and 14 sex- and age-matched controls. Despite significant increases in lymphocyte counts in both groups, lymphocyte subsets did not change accordingly. A wide scattering of catecholamine levels in plasma before and after stress was observed. Plasma levels of lymphokines such as interleukin (IL)-1 beta and IL-6 could not be detected in RA patients. Enzyme immunoassay of markers of lymphocyte activation such as HLA-DR and cell-bound IL 2 receptor showed only a significant elevation of HLA-DR marked cells in RA patients at baseline. Significantly higher amounts of the soluble IL-2 receptor were detected in patients with RA before the stress test, but stress testing did not alter this parameter. In conclusion, lymphocyte activation in RA and a defect in the expression of IL-2 receptor on the cell surface of lymphocytes were confirmed in the present study. PMID- 1459184 TI - Bidirectional communication between the brain and the immune system. AB - There is now a substantial body of data available indicating that the brain, the nervous system, and the immune system are functionally connected. Consequently, environmental conditions of a psychosocial or physical nature may influence the body's defence. The magnitude of the change in immune reactivity is partly determined by the individual's evaluation of the psychological or physical stimulus. This is illustrated by pharmacological modification of perception resulting in more pronounced stress-induced immunomodulation. In man, it has been demonstrated that recently experienced life stress, particularly daily hassles, can codetermine the effect of an experimental stressor applied for a short period of time on the immune system. An intriguing finding relates to the synthesis and secretion of hormones and neuropeptides by immune cells. These chemical messengers act as autocrine or paracrine immunoregulatory molecules on the one hand, and as messengers for communication with the brain and peripheral nervous system on the other. Animal research indicates that this dialogue is of biological significance. PMID- 1459185 TI - Interferon inducer, polyriboguanylic.polyribocytidylic acid, inhibits experimental hepatic metastases in mice. AB - The antitumour activity of an interferon inducer, the double-stranded complex of polyriboguanylic.polyribocytidylic acid was studied on murine lymphosarcoma LS/BL. The antitumour effect was determined with the aid of an experimental liver colony model and compared to that exhibited by another synthetic RNA, polyriboinosinic.polyribocytidylic acid. We found that both polynucleotide complexes decreased the number of liver colonies and prolonged the survival of the tumour-bearing mice. This effect was only observed if the complexes were applied in an appropriate dose schedule which included the administration of the drug prior to tumour cell inoculation and subsequent continuous treatment. We have also verified that the polynucleotide complexes did not exert their antitumour effect by a direct action on tumour cells. PMID- 1459186 TI - Effect of muscarinic cholinergic drugs on ischemia-induced decreases in glucose uptake and CA1 field potentials in rat hippocampus slices. AB - To clarify the role of muscarinic acetylcholine receptors in the hypoxia/hypoglycemia (ischemia)-induced functional deficit in hippocampal neurons, we examined the effect of cholinergic drugs on ischemia-induced impairments of glucose uptake and CA1 field potentials in hippocampus slices. Muscarinic receptors were subdivided into M1 (high affinity for pirenzepine) and M2 (low affinity for pirenzepine) subtypes. The M1 receptor subtype is coupled to an increase in phosphoinositide hydrolysis and the M2 receptor subtype is associated with inhibition of adenylate cyclase. The greater potency of carbachol in stimulating phosphoinositide hydrolysis resulted in exacerbated ischemia induced deficits. Treatment with the muscarinic receptor antagonists scopolamine and pirenzepine (M1 receptor-selective antagonist) had a strong dose-dependent protective effect against ischemia-induced deficits. Oxotremorine and McN-A-343, weak stimulators of phosphoinositide hydrolysis and strong inhibitors of adenylate cyclase, had a weak neuroprotective action against ischemia-induced deficits. These results suggest that stimulation of M1 muscarinic receptors coupled with an increase in phosphoinositide hydrolysis may play a facilitatory role in ischemia-induced deficits. Stimulation of M2 muscarinic receptors may play an inhibitory role in ischemia-induced neuronal deficits. PMID- 1459187 TI - A rodent model of focally evoked self-sustaining status epilepticus. AB - We describe a novel model of status epilepticus produced by the focal application of bicuculline methiodide into the deep prepiriform cortex of rats pretreated with lithium chloride. Three out of eight rats pretreated with one dose of lithium (3 mmol/kg) 24 h prior to induction of seizures by focal bicuculline, and eight out of 12 rats pretreated with two doses of lithium (at 24 and 48 h) prior to seizure induction, exhibited continual uninterrupted convulsive seizure activity (status epilepticus) lasting between 10 min and > 2 h. This status epilepticus which was manifest both behaviorally and electroencephalographically, was sensitive to reversal by diazepam (5 mg/kg i.p.) given as long as 2 h after the onset of sustained status epilepticus. Pilocarpine (25 mg/kg) pretreatment also predisposed to status epilepticus in response to the focal application of bicuculline, but diazepam (5 or 10 mg/kg i.p.) was ineffective in suppressing the status epilepticus in the presence of pilocarpine. PMID- 1459188 TI - Pharmacology of the 5-hydroxytryptamine-induced depolarization of the ferret vagus nerve in vitro. AB - Grease-gap recordings revealed that 5-hydroxytryptamine (5-HT) depolarized the ferret vagus nerve (pEC50 = 4.9). This response was mimicked by 2-methyl-5-HT and 1-phenylbiguanide, but not by 5-carboxamidotryptamine. Paroxetine (1 microM) or ketamine (10 microM) did not potentiate the response. Ketanserin (1 microM) did not reduce the depolarization, but four 5-HT3 receptor antagonists did. It is concluded that 5-HT depolarizes the ferret vagus nerve via 5-HT3 receptors, but these receptors may differ pharmacologically from those in other species. PMID- 1459189 TI - Evidence that 5-HT2 receptors predominantly mediate the contraction of the rat basilar artery to 5-hydroxytryptamine. AB - We characterised the 5-hydroxytryptamine (5-HT) receptor subtype which mediates the contraction of the rat isolated basilar artery, mounted in a myograph, by using agonists and antagonists for 5-HT1-like, 5-HT2, 5-HT3 and 5-HT4 receptors. The rank order of potency for a range of selective agonists was: 5-HT > alpha methyl-5-HT > 5-carboxamidotryptamine > 2-methyl-5-HT > sumatriptan. The maximum contractions for these agonists (Emax) was less than for 5-HT while 8-hydroxy-2 (di-n-propylamino)tetralin (8-OH-DPAT) was devoid of contractile activity. Ketanserin antagonised the contractile effect of 5-HT in the rat basilar artery with a provisional pA2 estimate of 9.3 +/- 0.2. A similar antagonism was observed against alpha-methyl-5-HT. Ergometrine (0.01-1 microM) was devoid of any agonist activity but antagonised the contractile effect of 5-HT on the rat basilar artery with a provisional pKB of 8.7 (7.8-9.8, 95% confidence limits). The 5-HT3 and 5 HT4 receptor antagonist ICS 205930 (10 microM) did not alter the response to 5 HT. The high potency and efficacy of alpha-methyl-5-HT, poor effect of sumatriptan and antagonism of 5-HT by ergometrine and ketanserin, support the conclusion that the 5-HT2 receptors are primarily responsible for the 5-HT induced contraction of rat basilar artery. PMID- 1459190 TI - Capsazepine inhibits low pH- and lactic acid-evoked release of calcitonin gene related peptide from sensory nerves in guinea-pig heart. AB - In the isolated perfused guinea-pig heart low-pH buffer (pH 5), lactic acid (5 mM), capsaicin (10(-7) M) and nicotine (10(-4) M) all evoked a clear-cut release of calcitonin gene-related peptide (CGRP) from sensory nerves. Incubation with the proposed capsaicin receptor antagonist, capsazepine (10(-5) M), significantly reduced the CGRP release evoked not only by capsaicin but also by low pH and lactic acid, indicating a common mechanism of C-fibre activation, while the nicotine response remained unchanged. PMID- 1459191 TI - Unmasking the vasoconstrictor response to neuropeptide Y and its interaction with vasodilating agents in vitro. AB - Neuropeptide Y (NPY) is a powerful vasoconstrictor in vivo but is usually much less active on isolated blood vessels. The contractile effect of NPY was examined in the isolated rat femoral artery exposed to various degrees of vasoconstriction. The effects of NPY on the relaxation induced by vasodilator agents was also studied. NPY (< or = 1 microM) had no contractile effect. In vessels pretreated with a low concentration of phenylephrine (0.3-1.0 microM), NPY evoked a concentration-dependent contraction, which was similar in intact and in endothelium-deprived vessels. Other vessels were contracted with phenylephrine (3-10 microM) and relaxed with histamine (0.1 mM). Subsequent addition of NPY elicited a contraction which was much greater than that observed in vessels pretreated with phenylephrine only. The Y1 receptor agonist, [Pro34]NPY, but not the Y2 receptor agonist, NPY 13-36, evoked a concentration-dependent contraction in phenylephrine-pretreated vessels. Acetylcholine (ACh) induced endothelium dependent relaxation in vessels contracted with phenylephrine. NPY (0.1 microM) induced a rightward shift of the concentration-response curve and a lower maximum relaxation in response to ACh. NPY was without effect on the dilatation evoked by nitroprusside, histamine or forskolin. In conclusion, under appropriate vasoconstrictor and vasodilator influence, NPY can act at Y1 receptors to evoke vasoconstriction in the femoral artery via endothelium-independent mechanisms. In addition, NPY seems to attenuate the endothelium-dependent relaxation induced by ACh. These actions of NPY may contribute to explain the strong vascular effects of the peptide in vivo. PMID- 1459192 TI - Protective effect of a selective endothelin receptor antagonist, BQ-123, in ischemic acute renal failure in rats. AB - To elucidate the pathophysiological role of endogenous endothelin (ET), we examined the effects of the newly synthesized ETA receptor-selective antagonist, BQ-123, on ischemic acute renal failure induced by bilateral clamping of renal artery and vein followed by reperfusion in rats. BQ-123, when given by i.v. infusion of 0.5 mg/kg per min for 2.5 h during the pre- and post-ischemic period, was found to prevent the decrease in creatinine clearance and increases in blood urea nitrogen, plasma creatinine and the fractional excretion of sodium. Morphological observation also showed an effect of BQ-123, i.e. prevention of proximal tubular (S3 segment) necrosis. At 2 h after the start of reperfusion, the ET-1 content in the kidney increased to its maximal level. At this time, the Ca2+ content in the mitochondrial fraction of the renal cortex increased, with a concomitant increase in blood urea nitrogen. However, these increases were limited by treatment with BQ-123. Thus, BQ-123 was effective to both prevent mitochondrial Ca2+ accumulation in the early phase of ischemic acute renal failure and protect proximal tubular cells from post-ischemic degeneration. We conclude that ET may be at least partially involved in the pathogenesis of tubular cell injury in this acute renal failure model. PMID- 1459193 TI - Histamine H1 receptors mediate vasodilation in guinea-pig ileum resistance vessels: characterization with computer-assisted videomicroscopy and new selective agonists. AB - Histamine receptors on guinea-pig ileum submucosal arterioles (outside diameter 40-80 microns) were studied in vitro using a computer-assisted videomicroscopy system (Diamtrak). Histamine receptor agonists investigated in this study were histamine, the H1 receptor-selective compound, 2-[2-(3-fluorophenyl)-4 imidazolyl]ethanamine (VZ 20), the H2 receptor-selective compounds, dimaprit, impromidine, (+/-)-N1-[3-(4-fluorophenyl)-3-(pyridin-2-yl)propyl]- N2-[3-(1H imidazol-4-yl)propyl]guanidine (arpromidine) and (+/-)-N1-[3-(3,4-difluorophenyl) 3-(pyridin-2-yl)propyl]- N2-[3-(1H-imidazol-4-yl)propyl]guanidine (BU-E-75), as well as the H3 receptor-selective drug, (R)-alpha-methylhistamine ((R)-alpha MeHA). Applied to vessels at resting tone, the agonists (1 nM-300 microM) did not change arteriolar diameter. Vessels preconstricted by 10 microM noradrenaline showed similar concentration-dependent vasodilations with histamine and VZ 20 (pD2 = 5.38 and 5.36, respectively). This histamine-induced vasodilation was not affected by tetrodotoxin (0.5 microM) or indomethacin (1 microM), but was completely abolished in the presence of 1 microM of the H1 receptor antagonist, mepyramine. Calculation of the antagonist affinity of mepyramine for the histamine receptors in submucosal arterioles yielded a pA2 of 9.46. In contrast to histamine and VZ 20, the H2 receptor agonist, dimaprit, and the H3 receptor agonist, (R)-alpha-MeHA, were ineffective at preconstricted arterioles. The guanidine-type H2 receptor agonists, impromidine, apromidine and BU-E-75, produced vasodilation at noradrenaline-preconstricted arterioles (-log EC50 = 4.47, 5.30 and 5.39, respectively) but, in contrast to histamine, were ineffective at arterioles preconstricted by U-46619 (300 nM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459194 TI - Tetronothiodin, a novel CCKB receptor ligand, antagonizes cholecystokinin-induced Ca2+ mobilization in a pituitary cell line. AB - We found a novel nonpeptide CCKB receptor antagonist, tetronothiodin (Ro 09 1468), in the culture broth of Streptomyces sp. NR0489. The structure of the compound (C31O8H38S), which has a 19-membered ring with an alpha-acyltetronic acid and tetrahydrothiophene moiety, is completely different from that of any known CCK receptor antagonist. Tetronothiodin inhibited [125I]CCK-8 binding to rat brain CCKB receptors with an IC50 of 3.6 nM, whereas it showed only weak affinity for rat CCKA receptors (IC50 = 70 microM). As demonstrated autoradiographically, tetronothiodin concentration dependently inhibited [125I]CCK-8 binding to CCKB receptors in rat forebrain slices. The effects of tetronothiodin on cytosolic Ca2+ concentrations in GH3 cells, a rat anterior pituitary tumor cell line, were investigated with the fura-2 method. Tetronothiodin inhibited CCK-8-induced Ca2+ mobilization without affecting basal cytosolic Ca2+ concentrations. In conclusion, tetronothiodin is a new, potent and highly selective CCKB receptor antagonist. It is a useful tool for investigating the pharmacological and physiological roles of CCKB receptors. PMID- 1459195 TI - Effects of exogenous wild-type p53 on a human lung carcinoma cell line with endogenous wild-type p53. AB - Several studies have shown that expression of exogenous wild-type p53 is detrimental to the growth of cell lines with absent or mutant p53. In this study, wild-type p53 cDNA expression plasmids were transfected into A549 lung carcinoma cells which had previously been shown by sequencing to contain wild-type p53. When a constitutively expressed wild-type p53 plasmid containing the neomycin resistance gene was transfected into these cells, no G418-resistant colonies contained the exogenous p53 cDNA even though the neomycin resistance gene was integrated. When cells were transfected with a dexamethasone-inducible wild-type p53 cDNA expression plasmid, induction of p53 expression resulted in a decreased growth rate and a decreased proportion of S-phase cells. Continuous treatment with dexamethasone resulted in continued p53 expression for 16 days, but beyond that time expression ceased and could not be reinduced. These data indicated that although the A549 cell line could proliferate in the presence of endogenous wild type p53 there was a strong selection pressure against continued expression of additional exogenous wild-type p53. PMID- 1459196 TI - Analysis of competence in cultured sea urchin micromeres. AB - Sea urchin embryo micromeres form the primary mesenchyme, the skeleton-producing cells of the embryo. Almost nothing is known about nature and timing of the embryonic cues which induce or initiate spicule formation by these cells. A related question concerns the competence of the micromeres to respond to the cues. To examine competence in this system we have exposed cultured sea urchin micromeres to an inducing medium containing horse serum for various periods of time and have identified a period when micromeres are competent to respond to serum and form spicules. This window, between 30 and 50 h after fertilization, corresponds to the time when mesenchyme cells in vivo are aggregating and beginning to form the syncytium in which the spicule will be deposited. The loss of competence after 50 h is not due to impaired cell health since protein synthesis at this time is not significantly different from controls. Likewise the accumulation of a spicule matrix mRNA (SM 50) and a cell surface glycoprotein (msp 130), both indices of micromere/mesenchyme differentiation, still occurs in cells that have lost competence to respond to serum by forming spicules. These experiments demonstrate that the acquisition and loss of competence in these cells are regulated developmental events and establish an in vitro system for the identification of the molecular basis for inductive signal recognition and signal transduction. PMID- 1459197 TI - Isolation and characterization of a brefeldin A-resistant mutant of monkey kidney Vero cells. AB - Brefeldin A (BFA) is a fungal antibiotic which disrupts protein transport between the endoplasmic reticulum and the Golgi. A BFA-resistant mutant of monkey kidney Vero cells, BER-40, which exhibited about a 90-fold increase in the LD50 of BFA (5.2 ng/ml for Vero cells versus 460 ng/ml for BER-40 cells), has been isolated. The increased resistance of BER-40 cells toward BFA was also manifested in a greatly reduced inhibition of protein secretion by BFA in the mutant and a lack of protection by BFA of the mutant cells from ricin cytotoxicity. Somatic cell hybridization between the Vero and BER-40 cells showed that the BFA-resistance in BER-40 behaved as a codominant trait. The structure of the Golgi region, as examined by immunofluorescence microscopy with antibodies against Golgi markers (the 110-kDa protein and mannosidase II) or with fluorescent lipid NBD-ceramide, was unchanged in the mutant cells as compared to that in the wild-type cells. Treatment of Vero cells with BFA (1 micrograms/ml) or with 2-deoxyglucose plus sodium azide resulted in a rapid release of the 110-kDa protein, mannosidase II, and NBD-ceramide from the Golgi membrane to a more diffuse distribution in the cytosol. In contrast, these three Golgi markers remained to be Golgi-associated following treatment of BER-40 cells with BFA or with 2-deoxyglucose plus sodium azide. Immunoblotting of cell extracts from Vero and BER-40 cells with monoclonal antibody against the 110-kDa protein did not reveal any significant difference in the level of this Golgi marker in the mutant cells. These data suggest that the BFA-resistance mutation in BER-40 has rendered the cyclic pathway of the 110-kDa protein assembly to the Golgi membrane resistant to both BFA and 2-deoxyglucose plus sodium azide. PMID- 1459198 TI - Evidence that oocyte maturation induced by an oncogenic ras-p21 protein and insulin is mediated by overlapping yet distinct mechanisms. AB - We have recently shown that a peptide (residues 35-47) from a functional region of the ras p21 protein, thought to be involved in the binding of p21 to GTPase activating protein, the antibiotic azatyrosine, known to induce the ras-recision gene, and the selective protein kinase C inhibitor, CGP 41,251, all inhibit oncogenic p21 protein-induced maturation of oocytes in a dose-dependent manner. We now show that these three agents only partially inhibit insulin-induced oocyte maturation, known to be dependent on activation of cellular p21 protein. On the other hand, the anti-p21 protein antibody Y13-259 completely inhibits both insulin- and oncogenic p21 protein-induced maturation as does a tetrapeptide, CVIM, known to block the enzyme farnesyl transferase which covalently attaches the farnesyl moiety to the p21 protein allowing it to attach to the cell membrane. Our results suggest that while the oncogenic and insulin-activated normal p21 proteins share certain elements of their signal transduction pathways in common, these pathways diverge and allow for selective inhibition of the oncogenic pathway. PMID- 1459199 TI - Metabolic consequences of adenine-phosphoribosyl transferase deficiency in V79 hamster fibroblasts. AB - Two APRT- clones (V79-E3 and V79-E1A) were isolated from V79 hamster fibroblasts treated with ethyl methanesulfonate. Selection involved sequential exposure of the mutagenized cells to the adenine analogues 8-azaadenine and 2,6 diaminopurine. To examine the influence of APRT deficiency on cell metabolism we determined the size and turnover of adenine ribonucleotide pools, the deoxyribonucleoside triphosphate pools, the rate of DNA synthesis, and the length of the cell cycle. Clone V79-E3 was hemizygous for aprt and carried a new chromosome, 3p-. Clone V79-E1A was quasi-tetraploid with a cell volume more than twice that of the WT cells. When the difference in size was taken into account, both clones behaved similarly. While WT V79 cells released no adenine into the medium, they excreted adenine at a rate of 6 pmol/min. This did not affect the size of the ATP pool. The main change in the deoxynucleotide pools was a marked decrease of the concentration of dCTP. The rate of DNA synthesis was the same in WT cells and in the diploid V79-E3 clone. APRT is known to recycle adenine produced during polyamine synthesis, but the enzyme apparently contributes little to the maintenance of adenine ribonucleotide pools of V79 fibroblasts. PMID- 1459200 TI - Localization by high resolution in situ hybridization of the ribosomal minichromosomes during the nucleolar cycle of Physarum polycephalum. AB - We have used biotinylated rDNA probes to localize by in situ hybridization the extrachromosomal genes for ribosomal RNA in the slime mold Physarum polycephalum. We established conditions that allow for highly specific hybridization at the ultrastructural level and determined that the 60-kb palindromic rDNA molecules are confined to the nucleolus in interphase. Our study definitively locates these extrachromosomal genes in mitosis in the form of thin DNA fibers contained within nucleolar remnants. We further show that these rDNA minichromosomes do not condense and that they segregate as entities independent of the condensed chromosomal DNA. In telophase, these minichromosomes migrate from the poles toward the equatorial region of the nucleus in a direction opposite that of the chromosomes. Our results illustrate the discontinuous nature of the nucleolar organizing region in Physarum. PMID- 1459201 TI - Cellular interactions with the extracellular matrix are coupled to diverse transmembrane signaling pathways. AB - Extracellular matrix (ECM) glycoproteins such as laminin, fibronectin, or collagen IV play a major role in cell behavior regulation. The molecular mechanisms taking place at the interface between the ECM and the cell surface are now rather well defined; however, very little is known about intracellular signals induced by these interactions. In order to get insights into the transduction pathways involved in cell-ECM interactions we have investigated the effects of several intracellular kinase inhibitors. Calmodulin-dependent kinase inhibitors, W-7 and sphingosine, have negative effects on cell-matrix interactions. They inhibit adhesion of several cell lines to laminin (IC50 = 4-10 microM), fibronectin and collagen IV (IC50 = 7-25 microM). The effects are immediate, reversible, and also cell specific, certain combinations of cell line substrate being irresponsive to these inhibitors. In contrast, two inhibitors, H 7 and staurosporine, for which protein kinase C is a common target, increase two- to fourfold the attachment of HT1080, OVCAR-4, and B16F10 cells to laminin but not to fibronectin. Another inhibitor, HA-1004, known to inhibit protein kinase A at low concentrations, has an activating effect only at high concentration (> 200 microM) when it becomes an inhibitor of protein kinase C. These inhibitors are without effect on RuGli and Saos-2 cell adhesion on the three substrates. Altogether these results suggest that calmodulin-dependent kinases and protein kinase C could be separately involved in ECM-induced cellular responses. However, the effects of kinase inhibitors are substrate-specific and cell type-specific, suggesting that the intracellular signals induced by the extracellular matrix vary with the nature of integrin involved in signal transmission. PMID- 1459202 TI - Nuclear colocalization of c-myc protein and hsp70 in cells transfected with human wild-type and mutant c-myc genes. AB - Using immunofluorescence and electron microscopy we have studied the localization of wild-type and mutant c-myc proteins transiently expressed in CV-1 cells. In agreement with our previous observations, wild-type c-myc protein accumulated in large amorphous globules in the nucleus. All mutant proteins tested accumulated in the nucleus as well, but gave rise to morphologically different inclusion bodies. Many small globules appeared in cells transfected with D145-262 (deletion of amino acids 145-262), while cells transfected with D371-412 or D414-433 generated structures looking like a fine network or like beads on a string. In addition, a particulate cytoplasmic staining appeared in some cells transfected with the wild-type gene and in cells transfected with mutants D145-262 or D414 433. Since the c-myc protein has been reported to stimulate expression of exogenous hsp70 protein, we also examined the intracellular distribution of hsp70 in the transfected cells. Double immunofluorescence microscopy revealed that hsp70 codistributed with the c-myc protein in distinct globules in the nucleus of many but not all myc-positive cells. However, the levels of hsp70 transcripts were not significantly raised compared to nontransfected and vector-transfected cells. Likewise, the levels of hsp70 protein did not vary significantly. These findings indicate that overexpression of c-myc stimulates translocation of preexisting hsp70 from the cytoplasm into the nucleus, rather than influencing hsp70 expression. Conceivably, this may represent one of several mechanisms whereby the cell deals with excessive amounts of c-myc protein. PMID- 1459203 TI - The effect of staurosporine, a protein kinase inhibitor, on asialoglycoprotein receptor endocytosis. AB - Receptor-mediated endocytosis via coated pits is modulated by the activity of protein kinases and protein phosphorylation. We examined the effects of the potent protein kinase inhibitor staurosporine (SSP) on endocytosis of the asialoglycoprotein (ASGP) receptor in HepG2 cells. Staurosporine caused a rapid (< 2 min) inhibition of ligand internalization from the cell surface. In contrast the rate of receptor exocytosis from intracellular compartments to the cell surface was not altered (t1/2 = 8 min). This resulted in increased ASGP receptors at the plasma membrane (140% of control) while the total number of receptors per cell was unchanged. Receptor up-regulation was half-maximal at 30 nM SSP. At this concentration staurosporine also inhibited the internalization of iodinated transferrin by HepG2 cells and SK Hep-1 cells, another human hepatoma-derived cell line. Staurosporine was without effect on the non-receptor-mediated uptake of Lucifer yellow by pinocytosis. We investigated the possible involvement of protein kinase C in the inhibitory effects of staurosporine on receptor endocytosis. The active protein kinase C inhibitor H7 did not inhibit ASGP receptor internalization. Furthermore depletion of cellular protein kinase C by overnight incubation with 1 microM phorbol myristate acetate did not abrogate the SSP effect. Together these data suggest that the mechanism of SSP action is independent of the inhibition of protein kinase C. In conclusion staurosporine is a potent and rapid inhibitor of receptor trafficking which is specific for receptor internalization from the plasma membrane. PMID- 1459204 TI - ORS12, a mammalian autonomously replicating DNA sequence, is present at the centromere of CV-1 cell chromosomes. AB - ors12, an 812-bp-long sequence, previously isolated by extrusion of nascent DNA from replication bubbles active at the onset of S phase (G. Kaufmann, M. Zannis Hadzopoulus, and R. G. Martin Mol. Cell. Biol. 5, 721-727, 1985), has been shown to function as an origin of DNA replication in autonomously replicating plasmids (L. Frappier and M. Zannis-Hadjopoulos Proc. Natl. Acad. Sci. USA 84, 6668-6672, 1987) and in a cell-free system (C. E. Pearson, L. Frappier, and M. Zannis Hadzopoulos Biochim. Biophys. Acta 1090, 156-166, 1991). A portion of ors12 (nucleotides 1-168) consists of the highly reiterated alpha-satellite sequence (B. S. Rao et al. Gene 87, 233-242, 1990). We have estimated the copy number of the non-alpha-satellite portion of ors12 in CV-1 cells to be < 9 copies per haploid genome and have used it as a probe to generate a genomic map of ors12 on CV-1 DNA. In situ hybridization of CV-1 metaphase chromosomes, using a biotinylated probe of the entire ors12 sequence, positively identified the centromeres of all chromosomes. However, when the non-alpha-satellite portion of ors12 was used as a probe, it positively identified the centromeric region of only six chromosomes, namely, B4, C11, D14, D24, E25, and E27, as well as that of a marker chromosome. The results suggest that ors12 represents a centromeric putative replication origin that is present on a subset of CV-1 chromosomes and is activated at the onset of S phase. PMID- 1459205 TI - Polyoma middle T antigen or v-src desensitizes human epidermal growth factor receptor function and interference by a monensin-resistant mutation in mouse Balb/3T3 cells. AB - Epidermal growth factor (EGF)-induced down-regulation of its receptor is an obligatory pathway for cellular regulation of EGF-specific receptor (EGF-R) in normal and malignant cells. BNER4 cells are mouse Balb/3T3 cells transfected with the human EGF-R complementary DNA (cDNA). Polyoma middle T antigen-transfectants of BNER4, B4/MT-2, B4/MT-13, B4/MT-23, and B4/MT-24, showed diminished down regulation of cell surface human EGF-R in response to EGF relative to the parental BNER4 cells. Also, the v-src-transfectants B4/SRC-13 and B4/SRC-24 showed much less down-regulation than BNER4 cells, whereas H-ras-transfectants of BNER4, B4/RAS-24 and B4/RAS-25, showed EGF-induced down-regulation of the cell surface EGF-R similar to that of BNER4. EGF induced DNA synthesis more than 20 fold in BNER4, but induced only about a 1.5- to 6-fold increase in the middle T antigen- and v-src-transfectants. EGF-Rs of the middle T antigen-transfectants were metabolically stable in the presence of EGF in comparison with their parental BNER4 cells. EGF-Rs of BNER4 cells degraded with half-lives of about 2 h in the presence of EGF, but those of the middle T antigen transformants were found to be highly stabilized in the presence of EGF. On the other hand, transfection with polyoma middle T antigen (MTAg) cDNA causes malignant transformation of Balb/3T3 cells, but not its monensin (an ionophoric antibiotic) resistant mutant MO-5 cells, which have no significant EGF binding activity. Transfection of human EGF-R cDNA into MO-5 leads to the expression of high levels of human EGF-R in MNER31. Unlike the polyoma MTAg transfectants of BNER4, EGF-R in polyoma MTAg cDNA-transfectants into MNER31, M31/MT-13 and M31/MT-14, were down-regulated to levels similar to those of their parental MNER31. Exposure to EGF induced a more than 10-fold increase in DNA synthesis of quiescent BNER4, MNER31, M31/MT-13, and M31/MT-14 cells. Polyoma middle T antigen or v-src appears to modulate EGF-induced down-regulation of EGF-R, possibly through interaction of the receptor with the viral oncogenes, and this interaction may be altered in the mutant. PMID- 1459207 TI - Inhibition of gliding movement by calcium in doublet microtubules on Tetrahymena ciliary dyneins in vitro. AB - We examined the effects of Ca ions on the gliding movement of Tetrahymena ciliary doublet microtubules induced by 14S or 22S dyneins in an in vitro motility assay system. The doublet microtubule appeared as circular-arc in solution, about 5 to 6 microns in length [1]. The doublet microtubules glided distal-end first on a 14S or 22S dynein-coated glass surface either clockwise or counterclockwise following the addition of ATP. The diameter of the circular path changed according to Ca concentration in the solution. Gliding velocity was from 1 to 5 microns/s. The addition of 0.1% Nonidet P-40 was necessary to induce the gliding movement on 22S dynein. This movement on 22S dynein was strongly inhibited above 0.5 mM ATP in the presence of 10(-9) M Ca, and at 0.05 to 1 mM ATP in the presence of 10(-3) M Ca. Many studies have indicated that Ca ions regulate ciliary movement [2-8] in which dyneins and doublet microtubule in the axoneme may play an essential role. The inhibition of the gliding movement of doublet microtubule on dyneins at appropriate concentrations of Ca and ATP as observed in this study may be the key for understanding Ca regulation of ciliary motility. PMID- 1459206 TI - Deficiency in integrin-mediated transmembrane signaling and microfilament stress fiber formation by aging dermal fibroblasts from normal and Down's syndrome patients. AB - Previous evidence has shown a deficiency in microfilament stress fiber formation upon short-term cycloheximide treatment of cultured human dermal fibroblasts while cytoplasmic spreading appeared completely normal and other cytoskeletal networks organized normally. This deficiency applied to collagen substrata (not fibronectin substrata) and was specific for in vitro-aged normal fibroblasts and for fibroblasts from three different Down's syndrome patients at any passage level. To identify the mechanism(s) for matrix receptor deficiency in aging cells, cells were evaluated for amounts and distributions of several integrin subunits using specific monoclonal antibodies and two complementary experimental approaches. Flow cytometric analyses have shown that all these cells at all passage levels have large amounts of alpha 3 and beta 1 integrin subunits and smaller amounts of the alpha 5 subunit, directed to fibronectin, which are minimally affected in their cell surface availability by cycloheximide treatment. In contrast, cycloheximide treatment leads to the loss from surface availability of most of the alpha 2 subunit, directed to collagen, in late-passage papillary and reticular normal fibroblasts and in all three Down's patient cells at all passages. Prior growth of cells in ascorbate-supplemented medium, which overcomes the deficiency in stress fiber formation, conserves the large amounts of cell surface-available alpha 2 subunit detectable by flow cytometry. When amounts of integrin subunits were evaluated by immunoprecipitation of [35S]methionine radiolabeled cells, there was no diminution of the alpha 2 subunit or any other subunit for any cells upon cycloheximide treatment; however, there was much less alpha 2 subunit complexed with beta 1 in aging normal and Down's cells. Therefore, cycloheximide treatment does not lead to loss in the amounts of the alpha 2 subunit but rather to its masking at the cell surface and inability to transmit signals across the plasma membrane to effect stress fiber formation. This aging-related deficiency in integrin-mediated signaling can now be studied mechanistically with a variety of approaches to determine the nature of cell surface molecules interacting with integrins (cis- and/or trans-acting molecules) that discriminate functional from nonfunctional receptors. PMID- 1459208 TI - The short-term increase in extracellular potassium concentration causes DNA replication onset in density-inhibited cells. AB - The high potassium concentration effect on the human diploid fibroblasts (HDF) and 3T3 cells was investigated. The incubation of confluent cultures of HDF or 3T3 Swiss cells in the medium with 50 mM K+ for 35 min induced, 12 h later, the onset of DNA replication in a significant proportion of culture cell population. The same treatment had no effect upon the sparce cell cultures. No stimulation of DNA replication was observed in the absence of serum in culture medium. PMID- 1459209 TI - Radiolabeling of DNA can induce its fragmentation in HL-60 human promyelocytic leukemic cells. AB - Incorporation of radiolabeled thymidine is commonly used to investigate DNA damage. Using a filter-binding assay, we observed that the addition of various doses of [methyl-3H]thymidine (0.2 and 2 microCi/ml) or [2-14C]thymidine (0.02 and 0.2 microCi/ml) in the culture medium for 2 days, a standard method for cell labeling, induces DNA fragmentation in HL-60 human promyelocytic cells. This effect was dose- and time-dependent and the DNA fragments were not protein-linked since the levels of DNA fragmentation were identical in the presence and in the absence of proteinase K (0.5 mg/ml). Radiolabeled thymidine-induced DNA fragmentation was associated with an inhibition of cell growth, but cells remained able to exclude trypan blue, suggesting that plasma membrane integrity was conserved, except at very high doses of [methyl-3H]thymidine (2 microCi/ml). By agarose-gel electrophoresis, the DNA-fragmentation was demonstrated to be internucleosomal with a typical ladder pattern. Addition of unlabeled thymidine to the culture medium prevented DNA fragmentation in a dose-dependent manner, indicating that radiolabeled thymidine incorporation in DNA was directly responsible for DNA fragmentation. We conclude that radiolabeling of DNA using thymidine incorporation can induce DNA fragmentation in some cell lines such as HL-60. This observation must be taken into account in methods using radiolabeling to study DNA damage in these cells. PMID- 1459210 TI - Basic FGF and TGF-beta differentially modulate integrin expression of human microvascular endothelial cells. AB - Basic fibroblast growth factor (bFGF) and transforming growth factor-beta (TGF beta) are known to alter the migratory and proliferative capacity of endothelial cells in vitro and to stimulate angiogenesis in vivo. One mechanism by which these cytokines induce their effects may be through the regulation of integrin adhesion receptor expression and activity. We examined the ability of these growth factors to modulate the expression of specific integrins in human microvascular endothelial cells (MEC). Immunoprecipitation of metabolically labeled MEC showed that bFGF upregulated the biosynthesis of alpha 2, alpha 5, beta 1, and beta 3. bFGF induced an increase in the levels of mRNA for alpha 2 and beta 1. TGF-beta increased synthesis of alpha 2, alpha 5, and beta 1. These results suggest that bFGF and TGF-beta selectively alter integrin profiles and influence interactions of MEC with the extracellular matrix during neovascularization. In particular, the upregulation of the collagen/laminin receptor, alpha 2 beta 1, by bFGF may provide activated endothelial cells with an enhanced capacity to migrate through both their underlying basement membrane and the interstitial matrix. PMID- 1459211 TI - Aging, longevity, and immortality in vitro. PMID- 1459212 TI - Genome reorganization through division: implications for aging of the mammalian organism. PMID- 1459213 TI - The telomere hypothesis of cellular aging. PMID- 1459214 TI - A somatic genetic approach to the analysis of senescence in human diploid fibroblasts in vitro: from heterokaryons to molecules. PMID- 1459215 TI - Oncogenes, protooncogenes, and tumor suppressor genes: a hitchhiker's guide to senescence? PMID- 1459216 TI - Altered expression of cell cycle dependent genes in senescent WI-38 cells. PMID- 1459217 TI - Inhibitors of DNA synthesis derived from senescent human diploid fibroblasts. PMID- 1459218 TI - Expression of prohibitin, an antiproliferative protein. PMID- 1459219 TI - Are all nonproliferating cells similar? PMID- 1459220 TI - Metalloproteinase and TIMP-1 gene expression during replicative senescence. PMID- 1459222 TI - Clonal attenuation and cell senescence: the next 30 years. PMID- 1459221 TI - Werner syndrome: molecular genetics and mechanistic hypotheses. PMID- 1459223 TI - Functional coupling of the stabilizing eye and head reflexes during horizontal and vertical linear motion in the cat. AB - The otolith contribution and otolith-visual interaction in eye and head stabilization were investigated in alert cats submitted to sinusoidal linear accelerations in three defined directions of space: up-down (Z motion), left right (Y motion), and forward-back (X motion). Otolith stimulation alone was performed in total darkness with stimulus frequency varying from 0.05 to 1.39 Hz at a constant half peak-to-peak amplitude of 0.145 m (corresponding acceleration range 0.0014-1.13 g). Optokinetic stimuli were provided by sinusoidally moving a pseudorandom visual pattern in the Z and Y directions, using a similar half peak to-peak amplitude (0.145 m, i.e., 16.1 degrees) in the 0.025-1.39 Hz frequency domain (corresponding velocity range 2.5 degrees-141 degrees/s). Congruent otolith-visual interaction (costimulation, CS) was produced by moving the cat in front of the earth-stationary visual pattern, while conflicting interaction was obtained by suppressing all visual motion cues during linear motion (visual stabilization method, VS, with cat and visual pattern moving together, in phase). Electromyographic (EMG) activity of antagonist neck extensor (splenius capitis) and flexor (longus capitis) muscles as well as horizontal and vertical eye movements (electro-oculography, EOG) were recorded in these different experimental conditions. Results showed that otolith-neck (ONR) and otolith ocular (OOR) responses were produced during pure otolith stimulation with relatively weak stimuli (0.036 g) in all directions tested. Both EMG and EOG response gain slightly increased, while response phase lead decreased (with respect to stimulus velocity) as stimulus frequency increased in the range 0.25 1.39 Hz. Otolith contribution to compensatory eye and neck responses increased with stimulus frequency, leading to EMG and EOG responses, which oppose the imposed displacement more and more. But the otolith system alone remained unable to produce perfect compensatory responses, even at the highest frequency tested. In contrast, optokinetic stimuli in the Z and Y directions evoked consistent and compensatory eye movement responses (OKR) in a lower frequency range (0.025-0.25 Hz). Increasing stimulus frequency induced strong gain reduction and phase lag. Oculo-neck coupling or eye-head synergy was found during optokinetic stimulation in the Z and Y directions. It was characterized by bilateral activation of neck extensors and flexors during upward and downward eye movements, respectively, and by ipsilateral activation of neck muscles during horizontal eye movements. These visually-induced neck responses seemed related to eye velocity signals. Dynamic properties of neck and eye responses were significantly improved when both inputs were combined (CS).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1459224 TI - Discharge properties of neurones in the hand area of primary somatosensory cortex in monkeys in relation to the performance of an active tactile discrimination task. II. Area 2 as compared to areas 3b and 1. AB - The discharge patterns of 144 single cortical neurones, within the cutaneous representation of the hand in area 2 (primary somatosensory cortex, SI), were studied in two rhesus monkeys during the performance of an active tactile discrimination task. These were compared to those previously described for units within areas 3b and 1 recorded from the same animals. The task consisted of making a single scanning movement of the digit tips over a surface (first half smooth; second half either smooth or rough). The nature of the texture encountered over the second half of the surface was indicated by the monkey making a differential lever response (push or pull) with the opposite hand. During the task, area 2 units with cutaneous receptive fields (RFs) on the digit tips of interest (those scanned over the surfaces) generally showed an increase in their discharge (75%); patterns of decreased discharge or no modulation (respectively, 12 and 13%) were rarely observed. Units with digital cutaneous RFs not in contact with the stimuli were much more likely to show either a pattern of decreased discharge or no modulation whatsoever (47% in each case), suggesting that there is some selection of cutaneous inputs in this task in that non-active inputs are selectively gated. For units with a cutaneous RF, the sign of modulation changed significantly across SI, in a manner consistent with a pattern of increased convergence onto the more caudal regions of SI. Overall, the proportions of area 2 units with digital RFs on the tips of interest that were classified as either texture-related (25%) or movement-related (26%) were similar to those reported previously for areas 3b and 1, suggesting that their presumed roles in, respectively, the analysis of surface texture and the representation of the physical parameters of movement are shared and distributed across the three cytoarchitectonic subdivisions of SI under consideration. In addition, the discharge patterns of single texture-related cells in areas 3b, 1 and 2 did not reliably signal whether or not the animal successfully discriminated the surfaces, suggesting that information from a population of cells is required for the performance of the task. Texture-related responses in area 2 were, however, unique in two ways. Firstly, 35% of the texture-related units had additional discharges related to the performance of the scanning movement (texture- and movement-related cells); no such units were found in area 3b, and only one was encountered in area 1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1459225 TI - Systemic tocainide relieves mechanical hypersensitivity and normalizes the responses of hyperexcitable dorsal horn wide-dynamic-range neurons after transient spinal cord ischemia in rats. AB - In the present study we examined the effect of systemic tocainide on sensory hypersensitivity in rats after spinal cord ischemia induced by a photochemical technique. After induction of spinal cord ischemia the rats exhibited a sensory disturbance which was mainly expressed as vocalization to innocuous cutaneous mechanical stimuli (allodynia) in the flank area during the following several days. Tocainide at 75 mg/kg i.p., but not 50 mg/kg i.p., significantly increased the vocalization threshold to mechanical pressure for 2 h. The effect of intraarterial (i.a.) tocainide on the responses of dorsal horn wide-dynamic-range (WDR) neurons to suprathreshold electrical stimulation of their receptive fields was also examined in normal rats and after transient spinal cord ischemia, at a time when the animals exhibited typical behavioral allodynia in the dermatomes innervated by the ischemic spinal segments. In normal rats, tocainide (50 mg/kg i.a.) strongly suppressed the responses of WDR neurons to C fiber input with lesser effect on A fiber input. In allodynic rats, tocainide suppressed the augmented A and C fiber mediated responses of WDR neurons to the extent that their responses were similar to those seen in normal rats without tocainide. There was no difference in the overall depression of A and C fiber mediated input by tocainide between normal and allodynic rats. The present results demonstrated the analgesic effect of systemic tocainide in relieving allodynia in rats and indicated that systemic local anesthetics, at doses that do not block nerve conduction, can be effective in suppressing dorsal horn WDR neuronal activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459226 TI - Low-threshold, short-latency cutaneous reflexes during fictive locomotion in the "semi-chronic" spinal cat. AB - Low-threshold, short-latency cutaneous reflexes evoked in ipsilateral hindlimb motor nerves were examined during fictive locomotion. Locomotion in 11 anaemically decerebrated spinal animals (1-3 weeks after transection at T13-L1) was induced by administration of clonidine, L-dopa and nialamide; by administration of the latter two drugs only; or by exteroceptive stimulation in the absence of any drugs. The caudal and lateral cutaneous sural, caudal cutaneous femoral, saphenous and superficial peroneal nerves were stimulated at low threshold (1.5-3 T). Pooled results from all combinations of cutaneous nerves stimulated and muscle nerves recorded show that the initial response was excitatory in 40 of 50 triceps surae and 17 of 20 semitendinosus (St) electroneurograms (ENGs). These excitatory responses occurred at latencies that ranged from 5 to 15 ms and tended to be maximal during the motor nerve's active period in the step cycle (i.e. they were modulated in a phase-dependent manner). Only three inhibitory responses (9-12 ms earliest latency) were encountered in total: in two St ENGs of one animal and in one lateral gastrocnemius-soleus ENG of a different animal. In two animals a "second" excitatory response (15-25 ms latency) was sometimes recorded in triceps surae and St nerves and, interestingly, could be modulated out of phase with the early response. Weak short-latency excitatory reflexes were also found in contralateral St ENGs when examined. Finally, among medial gastrocnemius, lateral gastrocnemius and soleus nerves, excitatory responses due to stimulation of any particular cutaneous nerve tended to be modulated similarly but were of consistently different amplitude among the three. This finding, together with the general observation that excitatory reflexes produced by stimulation of a particular cutaneous nerve were modulated similarly in extensors (or flexors) of different animals, suggests that spinal circuits generating locomotion may indeed exert a stereotypic control over interneurons in specific cutaneous reflex pathways to motoneurons. The results are primarily discussed in terms of the existing evidence for short-latency excitatory cutaneous reflexes in extensors in a variety of locomotive and non locomotive preparations. PMID- 1459227 TI - Observations on the development of transplanted embryonic ventral horn neurones grafted into adult rat spinal cord and connected to skeletal muscle implants via a peripheral nerve. AB - Embryonic spinal cord grafts from 12-day-old rat embryos were placed into the lumbar spinal cord of adult rats depleted of sciatic motoneurones by a neonatal nerve injury. A soleus muscle was removed from the leg and implanted paravertebrally, the proximal end of its nerve connected to the graft site. Fluorescent retrograde tracers injected into the soleus implant, 37-64 days postoperatively, labelled neurones that had grown axons to the muscle. Approximately one-fifth of retrogradely labelled neurons were within the graft; however, the majority were found within the host spinal cord close to the graft. These included large neurons within the motoneurone-depleted dorsolateral ventral horn. In control experiments a muscle and nerve were implanted but no embryonic tissue grafted. Significantly fewer neurones were labelled. In some animals, one tracer was injected into the soleus muscle whilst another was applied to the cut sciatic nerve ipsilateral to the graft site. No neurones were found to project axons to both targets. In animals that received grafts prelabelled with bromodeoxyuridine (BrDU) some neurones were found to be both BrDU positive and retrogradely labelled from the soleus implant. These were most frequently within the motoneuron-depleted ventral horn ipsilateral to the graft. Thus, grafted neurones may migrate to an appropriate location within the host neuropil. Acetylcholinesterase (AChE) histochemistry showed the graft site contained immature but AChE-positive neurones. Some regions of host ventral horn contained unusually few AChE-positive nerve fibres and occasional large AChE-positive neurones, some of which were also retrogradely labelled from the implanted muscle. Studies of implanted soleus 21-90 days after transplantation showed that muscle fibres, after initial degeneration, regenerated displaying differing phenotypes, presumably under the influence of new motor innervation. PMID- 1459228 TI - Responses of barrel cortex neurons in awake rats and effects of urethane anesthesia. AB - A "barrel" is an interconnected network of layer IV neurons that is an important component of a functional cortical column in the whisker area of the rodent primary somatosensory cortex. The present study was undertaken in order to resolve apparently conflicting findings from single-unit studies of barrel neurons conducted in rats maintained under different anesthetic conditions. Multiunit responses to controlled deflections of mystacial vibrissae were recorded from the whisker/barrel cortex of awake, undrugged rats, and responses at the same recording site were reexamined after the animal was anesthetized with urethane. In contrast to the awake condition, stimulus-evoked responses under urethane were characterized by a large late component. Such effects were more pronounced for deflections of noncolumnar or "adjacent" whiskers than for the columnar whisker. Latencies to peak responses were virtually identical for the columnar whisker in awake and urethane states (11.9 vs 11.8 ms) but were considerably longer for adjacent whisker deflections in urethane-anesthetized animals (15.5 vs 29.0 ms). The magnitudes of adjacent whisker responses, relative to the response evoked by the columnar whisker, varied with the laminar location of the recording site in awake but not in urethane-anesthetized animals; in awake rats, receptive fields were clearly smallest in the layer IV barrels. Results in the awake condition confirm those of previous studies conducted in unanesthetized or lightly sedated animals, and data obtained with urethane are comparable to others' results in urethane-anesthetized rats. The former have important implications for how barrel cortex processes information in behaving animals. PMID- 1459229 TI - Pretectal jerk neuron activity during saccadic eye movements and visual stimulations in the cat. AB - The activity of 'jerk neurons' was recorded extracellularly in the pretectum of the awake cat. The characteristic response of jerk neurons was a short, high frequency burst that occurred after fast movements ('jerks') of a large, structured visual stimulus, during saccadic eye movements in the light, and after 'on' or 'off' visual stimulation. Mean burst latency to pure visual 'jerks' was 50 ms, whereas it was 30 ms to saccadic eye movements. Bursts were found to be stereotyped; the highest discharge rate was always at burst onset. Jerk neurons were not selective for stimulus parameters (such as movement amplitude or direction) except that in some neurons a weak correlation between stimulus velocity and discharge frequency was found. During saccades in the dark, clear bursts were only rarely found. In about half of the neurons, however, there was a slight but significant increase in the number of spikes above spontaneous frequency. Visual receptive fields were very large (46 degrees horizontal and 35 degrees vertical extent, on average). Nevertheless, the pretectal jerk neurons showed a rough retinotopic order, which was in accordance with the published retinotopy of the pretectum. Jerk neurons were found throughout the whole superficial pretectum, but preferentially in an area that corresponds to the nucleus of the optic tract (NOT) and the nucleus pretectalis posterior (NPP). Saccades were elicited by electrical stimulations at the sites where jerk neurons were recorded. The direction of the elicited saccades depended strongly on the pretectal stimulation site. A possible role of the jerk neurons as a visuomotor relay to elicit saccades or to modulate perception and attention is discussed. PMID- 1459230 TI - Transcallosally evoked responses in the visual cortex of normal and monocularly enucleated rabbits. AB - In visual cortex of normal adult rabbits, callosal projections are restricted to a 2 mm wide band at the area 17/18 border. In adult rabbits which are monocularly enucleated (ME) on the day of birth, the callosal zone extends 4 mm into the medial region of area 17 in the cortex ipsilateral to the remaining eye. In this study, the function of these anomalous callosal projections in ME rabbits was investigated using electrophysiological techniques. A microelectrode was placed in the visual cortex ipsilateral to the enucleated eye at the 17/18 border, bipolar stimulating electrodes were placed in a homotopic location in the contralateral cortex, and averaged evoked responses (AERs) to stimulation were recorded. The stimulating electrodes were then moved mediolaterally in 1 mm steps, and the AERs were recorded for each location of the stimulating electrodes. In the normal rabbit, a maximal short latency evoked response was recorded when the stimulating electrodes were at a location homotopic to the recording electrode. When the stimulating electrodes were moved a distance of 1 mm or more from this optimal position, this short latency response was either absent or dramatically decreased in amplitude, reflecting the precise topographic pattern of the normal callosal projection. In contrast, in ME rabbits, a consistent response was evoked at the 17/18 border when the stimulating electrodes were moved as much as 3 mm medial to the homotopic position. Since antidromically activated responses and both pre- and postsynaptic orthodromically activated responses contribute to the AER, recordings were also made from single cells in some animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459231 TI - The effects of monocular enucleation on visual topography in area 17 in the rabbit. AB - The effects of neonatal monocular enucleation on the topographic representation of the ipsilateral visual field in the visual cortex of the rabbit were investigated, using electrophysiological recordings of multi-unit activity in area 17. Topography of receptive fields was determined in normal adult rabbits, adult rabbits monocularly enucleated on the day of birth and adult rabbits monocularly enucleated as adults. In normal rabbits and in adult enucleates, the projection from the ipsilateral eye is represented by a strip of cortex extending approximately 2 mm from the 17/18 border. In neonatal enucleates, the width of the area of cortex in which the projection from the ipsilateral eye is represented was approximately twice as large as normal. Visual topography was normal in the superior-inferior axis but was distorted in the nasotemporal axis. Our data suggest that the abnormal topography observed in the visual cortex of neonatally enucleated rabbits may play a major role in shaping the abnormal visual callosal projections observed in these animals. In addition, our data indicate that, following neonatal monocular enucleation, developmental abnormalities in the topography of geniculocortical projections can occur independently of any alteration in the retinogeniculate projection patterns. PMID- 1459232 TI - Pattern of projections of group I afferents from elbow muscles to motoneurones supplying wrist muscles in man. AB - The pattern of projections of low threshold afferents from triceps and biceps brachii muscles onto motoneurones innervating muscles acting at the wrist was assessed by a reflex and a poststimulus time histogram (psth) technique. Activation of low-threshold afferents originating from elbow flexors or extensors resulted in an early, short-lasting inhibition of wrist flexor motoneurones (flexor carpi radialis, flexor carpi ulnaris). An inhibition was also found in the extensor carpi radialis (ECR) motoneurones after stimulation of low-threshold afferents from triceps. Evidence is presented that Ia fibres contribute to these effects. The inhibitory effects were found in all subjects, but they were constant in only 57% of the reflex experimental sessions and in 25% of the explored motor units. Stimulation of biceps low-threshold afferents was always ineffective on ECR motoneurones. No early facilitation was ever seen in motor nuclei innervating wrist muscles following stimulation of low threshold afferents from biceps and triceps. The pattern of transjoint projections of group I afferents from proximal to distal muscles and from distal to proximal ones (Cavallari and Katz 1989) is discussed in relation to that described in the cat forelimb. PMID- 1459234 TI - Synergistic finger movements in a skilled motor task. AB - When skilled typists strike one key, typically all of the fingers of one hand are in motion simultaneously. We studied the extent to which the motion of the individual fingers was similar. Subjects were asked to type lists of words, each word designed so that only one key would be pressed by a finger of one hand, the remaining letters being typed with the other hand. Changes in the lengths (flexion-extension) and orientation (abduction-adduction) of each finger were measured and the similarity of the motion of pairs of fingers was assessed by computing correlation coefficients. For each pair of fingers, the correlation coefficients were broadly distributed, but in most instances the mean was significantly greater than zero. Adjacent fingers showed a higher degree of correlation than did non-adjacent fingers. When one of the fingers was actually used to press the key, the degree of correlation decreased substantially. The results demonstrate that in this skilled motor task, the fingers usually tend to be moved together, but they can be moved independently when the task so requires. PMID- 1459233 TI - The transcortical nature of the late reflex responses in human small hand muscle to digital nerve stimulation. AB - The hypothesis that long-latency reflex activity in human small hand muscles in response to stimulation of digital nerves involves a transcortical pathway was tested by combining digital nerve stimulation and magnetic stimulation over the motor cortex in 12 studies on nine normal subjects. Postsynaptic events in human single first dorsal interosseous (FDI) motoneurones were derived from changes in the firing probability of voluntarily activated single motor units. Electromagnetic stimulation over the contralateral motor cortex resulted in a short-latency, brief facilitation of FDI motor units considered to be due to the activation of "fast" corticospinal neurones making monosynaptic projections to motoneurones. Stimulation of the digital nerves of the index finger produced a period of reduced firing probability (I1), a period of increased firing probability (E2) and a further period of reduced firing probability (I2) in FDI motor units. When the two stimuli were given separately and then together, timed so that the magnetic stimulus occurred at the predicted transit time of the E2 through the cortex, the facilitation of FDI motoneurones by the combined stimulation was often less than the algebraic sum of the facilitations from each stimulus alone. Thus, in contrast to the results of similar studies on the late response to muscle stretch, there is no confirmation that the E2 from digital nerve stimulation is due to a transcortical reflex. PMID- 1459235 TI - Bidirectional control of saccadic eye movements by the disconnected cerebral hemispheres. AB - The present investigation demonstrates that callosotomy patient J.W. can generate either leftward or rightward saccades in response to color cues presented unilaterally. When asked to name the colors, performance was at chance for left visual field presentations, demonstrating a disability in interhemispheric transfer of chromatic information. The successful control of saccadic direction based on discriminative color cues that appear confined to a single hemisphere may suggest a capacity for bidirectional control of saccadic eye movements in the disconnected cerebral hemispheres. PMID- 1459236 TI - The vertex-positive scalp potential evoked by faces and by objects. AB - The influence of stimulus form on the scalp-recorded "vertex positive peak" (VPP) evoked by images of faces (Jeffreys 1989a) was studied in seven subjects. In separate experiments, we recorded the responses to 2D images of: (1) many different depictions of human faces; (2) the heads of several different species; (3) many familiar non-face objects; and (4) stimuli where the configuration of objects were modified to produce an "illusory" or "non-contextual" subjective impression of a face. The results showed that every facial representation, including the "illusory" stimuli, and most of the non-face objects, evoked a VPP of corresponding form and scalp distribution. The object-evoked VPPs, however, were always smaller and usually later than those evoked by the faces. VPPs of longer latency but often comparable amplitude were also recorded for impoverished compared to well-defined facial representations; and for most non-human compared to human faces. Very consistent responses were recorded to repeated presentations of the same stimulus for the same subject, but there was considerable variation in latency as well as amplitude (but not form) of the VPP evoked under identical experimental conditions for different subjects. These response properties of the VPP, suggest that its underlying physiological generators are sensitive to basic configural properties of the visual stimulus; and also the face- and object related information are processed in the same brain area(s), although not necessarily by the same physiological mechanisms. PMID- 1459237 TI - Evoked potential evidence for human brain mechanisms that respond to single, fixated faces. AB - The influence of visual fixation position and stimulus size on the scalp-recorded "vertex positive peak" (VPP) evoked by images of faces was studied in three subjects. Responses were recorded, in turn, for line-drawn, frontal-view faces of approximately 8, 4, 2, and 1 deg length, fixated at the centre (bridge of the nose), and at points 1, 2, 3, and 4 deg to the left and right, and above and below, centre. The results showed that central fixation produced VPPs of similar, maximal amplitude for all face sizes. By comparison, "on-face" eccentric viewing yielded attenuated and delayed responses, and the degree of response attenuation as a function of eccentricity was directly related to the face size, with similar amplitude responses being evoked for corresponding fixation locations on each face. Very small or no VPPs were recorded for most "off-face" fixations. Similar results were observed for profile faces, except that the maximal VPP was recorded for fixations near the eyes and not in the centre of the head, and almost identical VPPs were evoked by a centrally fixated face presented with and without an adjacent face or object. These response properties, which correspond to the subjective perception of the facial stimuli, suggest that the VPP reflects brain mechanisms optimized to respond to single, fixated faces, irrespective both of facial image size and of the presence of neighbouring figures. PMID- 1459238 TI - Do G protein subunits associate via a three-stranded coiled coil? AB - We used a computer-based prediction algorithm to identify probable coiled-coil segments at the N-termini of G protein alpha, beta and gamma subunits. This result indicates that G protein trimers may form via a three-stranded coiled coil. Previous biochemical results had shown that the N-termini of alpha and beta are involved in subunit interactions. Here we present a structural model for the N-terminal domain of beta gamma and a hypothesis for the reversible association of alpha to beta gamma. PMID- 1459239 TI - Site-directed mutation makes rabbit calcyclin dimer. AB - Unlike human, rat and mouse calcyclin, purified rabbit calcyclin did not form a dimer on Tricine SDS-PAGE under non-reduced conditions. Based on the internal peptide sequence of rabbit calcylin, we isolated and sequenced a cDNA clone encoding calcyclin. The sequence of this clone (pCalC) is 629 bp long and codes 90 amino acid residues of a protein with a molecular mass of 10,153 Da. By Northern blot analysis, a major band of 0.9 kbp and a minor band of 2.6 kbp were detected in the lung. The recombinant calcyclin mutated serine at the third position to cysteine was expressed in E. coli and made dimer formation under non reduced conditions on SDS-PAGE. Whether or not this type of mutation which prevents dimer formation of calcyclin plays a physiological role in the rabbit lung is the subject of an ongoing study. PMID- 1459240 TI - Amiloride at pH 7.0 inhibits the Na(+)-driven flagellar motors of Vibrio alginolyticus but allows cell growth. AB - Amiloride, a specific inhibitor for the Na(+)-driven flagellar motors of alkalophilic Bacillus, is known to inhibit secondarily the growth of alkalophiles. The motility of a marine Vibrio, V. alginolyticus, was almost completely inhibited by 2 mM amiloride either at pH 7.0 or 8.5. We found that this concentration of amiloride inhibited the cell growth completely at pH 8.5 but only slightly at pH 7.0. Kinetic analysis of the inhibition of motility by amiloride at pH 7.0 showed that the inhibition was competitive with Na+ in the medium. Thus, amiloride at pH 7.0 is really a specific and useful tool for the analysis of the Na(+)-driven flagellar motors of Vibrio. PMID- 1459241 TI - Determination of proteinase 3-alpha 1-antitrypsin complexes in inflammatory fluids. AB - Physiological inhibitors were tested for their in vitro interaction with neutrophil proteinase 3 (PR3). The major plasma proteinase inhibitor of PR3 is alpha 1AT. We have developed a radioimmunoassay (RIA) for quantitative detection of PR3-alpha 1AT complexes formed in vivo in inflammatory exudates such as synovial fluid and plasma from patients with sepsis. Levels of PR3-alpha 1AT complexes correlated significantly with levels of human neutrophil elastase (HNE) alpha 1AT complexes. Thus, in vivo alpha 1AT not only protects against excessive HNE activity, but also against excessive PR3 activity. PMID- 1459242 TI - Chromogranin A processing in sympathetic neurons and release of chromogranin A fragments from sheep spleen. AB - Chromogranin A (CGA) has been localized to the large dense cored vesicles (LDV) of sympathetic neurons. SDS-PAGE and immunoblotting of soluble LDV proteins from ox and dog adrenergic neuronal cell bodies, axons and nerve terminals, revealed an increasing number of CGA-immunoreactive forms, consistent with proteolytic processing during axonal transport. Splenic nerve electrical stimulation (10 Hz, 2 min) revealed that, apart from CGA, these CGA-processing products are released from the sheep spleen. The secretion of CGA-derived fragments from sympathetic neurons might suggest a role in the regulation of synaptic transmission. PMID- 1459243 TI - Detection of an enzyme bound gamma-glutamyl acyl ester of carbamyl phosphate synthetase of Escherichia coli. AB - E. coli carbamyl phosphate synthetase binds 0.2-0.4 mol equivalents of glutamine in an acid resistant form. The bound material is quantitatively released as glutamate by weak base hydrolysis and as a mixture of 12% glutamate, 10% gamma glutamylhydroxamate, and 70% pyrrollidonecarboxylic acid by hydrolysis with hydroxylamine. These results provide direct evidence for a gamma-glutamyl acyl ester on the enzyme. The absence of the acyl ester in a mutant carbamyl phosphate synthetase with a Cys269-->Ser substitution in the glutaminase subunit further suggests that the covalent intermediate is a thioester of Cys269. Under equilibrium conditions, the Cys269Ser mutant enzyme binds glutamine with a Kd of 7 +/- 1 microM, indicating that Cys269 is essential for acyl ester formation but not for binding of glutamine. PMID- 1459244 TI - Identification of the active site serine of the X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis. AB - The active site serine of the X-prolyl dipeptidyl aminopeptidase from Lactococcus lactis (PepX) was identified. The enzyme was labeled by [3H]DFP, treated by CNBr and the resulting peptides were separated by reverse-phase-HPLC. The main radiolabeled peptide was sequenced. Ser-348, in the following sequence, Gly-Lys Ser-Tyr-Leu-Gly, was identified as the active site serine. A sequence comparison between the active site of PepX and other serine proteases was made, showing only limited sequence homologies in this area. The consensus sequence surrounding the active site serine in the three known X-prolyl dipeptidyl aminopeptidases (mammalian DPPIV, yeast DPAB and PepX) is G-X-S-Y-X-G, where X is a non-conserved amino acid. PMID- 1459245 TI - Annexin V forms calcium-dependent trimeric units on phospholipid vesicles. AB - The quaternary structure of annexin V, a calcium-dependent phospholipid binding protein, was investigated by chemical cross-linking. Calcium was found to induce the formation of trimers, hexamers, and higher aggregates only when anionic phospholipids were present. Oligomerization occurred under the same conditions annexin-vesicle binding. A model is proposed in which cell stimulation leads to calcium-induced organization of arrays of annexin V lining the inner membrane surface, thus altering properties such as permeability and fluidity. PMID- 1459246 TI - Retinoic acid enhances the secretion of plasminogen from cultured rat microglia. AB - To determine the amount of plasminogen in microglial conditioned medium, a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for rat plasminogen was established. Weak cross-reactivity with human serum plasminogen was observed, while no reactivity was detected with frog and carp plasminogen. The specificity of the immunosorbent assay was confirmed by Western blotting. The secretion of plasminogen into the microglial culture medium was quantified by using the established ELISA and was found to be increased depending on the culture time and number of microglia. The secretion was increased about 5-fold by stimulation with retinoic acid, while interleukin-1, and basic fibroblast growth factor showed no significant effect. PMID- 1459247 TI - Protein structural effects of agonist binding to the nicotinic acetylcholine receptor. AB - The effects on the protein structure produced by binding of cholinergic agonists to purified acetylcholine receptor (AcChR) reconstituted into lipid vesicles, has been studied by Fourier-transform infrared spectroscopy and differential scanning calorimetry. Spectral changes in the conformationally sensitive amide I infrared band indicates that the exposure of the AcChR to the agonist carbamylcholine, under conditions which drive the AcChR into the desensitized state, produces alterations in the protein secondary structure. Quantitative estimation of these agonist-induced alterations by band-fitting analysis of the amide I spectral band reveals no appreciable changes in the percent of alpha-helix, but a decrease in beta-sheet structure, concomitant with an increase in less ordered structures. Additionally, agonist binding results in a concentration-dependent increase in the protein thermal stability, as indicated by the temperature dependence of the protein infrared spectrum and by calorimetric analysis, which further suggest that AcChR desensitization induced by the cholinergic agonist implies significant rearrangements in the protein structure. PMID- 1459248 TI - Identification of four FGF receptor genes in Medaka fish (Oryzias latipes). AB - Four types of cDNA clones encoding tyrosine kinases highly homologous to mammalian fibroblast growth factor receptors (FGF-R) were isolated from Medaka fish (Oryzias latipes) by the reverse transcription-polymerase chain reaction. Comparison of the four deduced amino acid sequences with four known mammalian FGF Rs indicated that four FGF-R species corresponding to mammalian FGF-Rs exist universally in vertebrates including fishes, although FGF-R4 might have diverged sequences between fishes and mammals. Each of four FGF-R genes is transcribed to various extents as multiple mRNAs possibly by alternative splicing in adult fishes. PMID- 1459249 TI - A mechanism for NADPH inhibition of catalase compound II formation. AB - Catalase-bound NADPH both prevents and reverses the accumulation of inactive bovine liver catalase peroxide compound II generated by 'endogenous' donors under conditions of steady H2O2 formation without reacting rapidly with either compound I or compound II. It thus differs both from classical 2-electron donors of the ethanol type, and from 1-electron donors of the ferrocyanide/phenol type. NADPH also inhibits compound II formation induced by the exogenous one-electron donor ferrocyanide. A catalase reaction scheme is proposed in which the initial formation of compound II from compound I involves production of a neighbouring radical species. NADPH blocks the final formation of stable compound II by reacting as a 2-electron donor to compound II and to this free radical. The proposed behaviour resembles that of labile free radicals formed in cytochrome c peroxidase and myoglobin. Such radical migration patterns within haem enzymes are increasingly common motifs. PMID- 1459250 TI - Beta-glucosidase activity towards a bile acid glucoside in human liver. AB - Human liver contains hydrolytic activity toward 3 beta-glucosido-chenodeoxycholic acid. This beta-glucosidase activity, localized predominantly in the microsomal fraction, was optimally active in the presence of divalent metal ions close to pH 5.0 and was inhibited by EDTA. Kinetic parameters and other catalytic properties of hydrolytic activity towards 3 beta-glucosido-chenodeoxycholic acid from human liver microsomes are described. PMID- 1459251 TI - cDNA sequence analysis of an antibiotic dodecapeptide from neutrophils. AB - The full-length cDNA of a neutrophil antibiotic dodecapeptide has been cloned by reverse transcription/PCR from bovine bone marrow RNA. This peptide was originally isolated from bovine neutrophils, and shown to exert a potent antimicrobial activity in vitro on both Escherichia coli and Staphylococcus aureus. The cDNA codes for a polypeptide of 155 amino acid residues with a predicted mass of 17,629 Da and a pI of 8.03. The deduced sequence comprises a putative signal peptide of 29 amino acids, a 114 residue pro-region, and a carboxy-terminal dodecapeptide corresponding to the mature antibiotic. The pro sequence displays extensive identity to corresponding regions of other structurally unrelated antibiotic peptides of bovine neutrophils recently cloned. PMID- 1459252 TI - Talin anchors and nucleates actin filaments at lipid membranes. A direct demonstration. AB - Platelet talin nucleates actin assembly as we show here directly by using rhodamine-phalloidin labelling of actin filaments. Nucleation by talin still occurs after reconstitution into liposomal bilayers. This is also demonstrated directly after protein-lipid double labelling and light microscopic imaging. Talin, thus, is the first actin binding protein for which anchoring and nucleation of actin filament growth at lipid interfaces have been visualized. PMID- 1459253 TI - Cytokines--involvement in reproduction. AB - OBJECTIVE: To relay the current knowledge on the interaction between the immune and reproductive systems that results from sharing certain lymphohematopoietic cytokines and their receptors. DATA IDENTIFICATION: Major studies related to this topic have been identified through MEDLINE searches and through the published literature. STUDY SELECTION: Those that have reported on the role of cytokines in the neuroendocrine events of reproduction, ovarian function, placenta, and the developing embryo. RESULTS: The field of growth factor and cytokines and their effects on reproduction is a rapidly growing new area of investigation. Immune cells and related cytokines have been shown to affect the neuroendocrine events of reproduction, ovarian function, placenta, and the developing embryo. Furthermore, it is now becoming apparent that these relationships are reciprocal in that the different cellular components of the neuroendocrine and reproductive systems and the developing embryo can modulate the production of cytokine by the immune system and can also produce certain cytokines. The presence of lymphocytes and macrophages in the female reproductive system, together with the fact that these cells may secrete soluble factors influencing embryo development and trophoblast growth, might suggest that cytokines may play a fundamental role in the mechanisms of immunological reproductive failure. In addition, different mixtures of these mediators, generated by immune cells, the developing embryo, or other maternal cells, may modulate the fine tuning of these activities. CONCLUSIONS: Current knowledge indicates a close interaction between the immune and reproductive functions. Further understanding of these interactions may lead to new concepts in fertility regulation. PMID- 1459254 TI - Operative endoscopy: the pressing need for a structured training and credentialing process. PMID- 1459255 TI - Pituitary function before, during, and after chronic gonadotropin-releasing hormone agonist therapy. AB - OBJECTIVE: To examine possible adverse effects on pituitary function of long-term administration of gonadotropin-releasing hormone agonist (GnRH-a). DESIGN: Prospective analysis of blood sampling before, during, and after GnRH-a therapy. SETTING: Tertiary institutional outpatient care. PATIENTS: Twelve normally ovulatory women with a diagnosis of endometriosis. INTERVENTIONS: Six-month suppression with GnRH-a. MAIN OUTCOME MEASURES: Serum levels of follicle stimulating hormone, luteinizing hormone, free thyroxin index, cortisol (F), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH). RESULTS: Basal and stimulated values of gonadotropins, PRL, F, TSH, and GH were normal and unchanged by 6 months of GnRH-a after resumption of menses. CONCLUSIONS: Utilizing dynamic pituitary function tests, we were unable to demonstrate an adverse effect of long-term GnRH-a therapy on pituitary function. PMID- 1459256 TI - Effect of human corticotropin-releasing hormone on gonadotropin secretion in cycling and postmenopausal women. AB - OBJECTIVE: To test the hypothesis that corticotropin-releasing hormone (CRH) is linked to stress-associated reproductive dysfunction in the human by determining if the administration of human corticotropin-releasing hormone (hCRH) results in an inhibition of gonadotropin secretion. DESIGN: Twenty-four-hour prospective study with frequent (every 10 minutes) blood sampling. SETTING: University Clinical Research Center. INTERVENTIONS: Sequential 8-hour infusions of normal saline, hCRH (1 to 5 micrograms/kg per hour), and hCRH plus naloxone (2 mg/h). SUBJECTS: Four normal cycling women and four postmenopausal women. MAIN OUTCOME MEASURES: Plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and adrenal and ovarian steroids. RESULTS: In response to hCRH, a prompt and sustained rise in cortisol (F) was noted in both normal cycling women and postmenopausal women. No inhibition of LH or FSH was noted during either the hCRH or hCRH plus naloxone infusion in either group of women. Unexpectedly, elevations in the mean LH peak amplitude and the transverse mean LH concentration were noted in the postmenopausal women during the infusion of hCRH as compared with saline. The infusion of hCRH had no apparent effect on concentrations of PRL, FSH, and gonadal and adrenal steroids (except for F). CONCLUSIONS: Under these conditions, intravenously administered hCRH has no inhibitory effect on gonadotropin secretion in either premenopausal or postmenopausal women. The mechanism by which stress exerts its deleterious effect on reproductive function in the human remains unknown. PMID- 1459257 TI - Influence of basal androgen levels in euandrogenic women on glucose homeostasis. AB - OBJECTIVE: To evaluate possible relationships between insulin action and the normal variations of serum androgens in euandrogenic women. DESIGN: Prospective evaluation of insulin action in normal nonobese women using hyperglycemic and euglycemic hyperinsulinemic clamp techniques, correlating insulin action to serum testosterone (T), free T, androstenedione (A), and dehydroepiandrosterone sulfate (DHEAS). Statistical analysis used Spearman's rank correlation. SETTING: Yale University Clinical Research Center. PARTICIPANTS: Nonobese females with normal oral glucose tolerance tests, on no medications known to affect glucose metabolism, having the following range of serum androgen levels: T, 0.69 to 3.12 nmol/L; free T, 0.17 to 1.25 nmol/L; A, 2.48 to 11.31 nmol/L; DHEAS, 0.68 to 10.61 mumol/L. Total number of patients studied: hyperglycemic clamps, n = 58; euglycemic hyperinsulinemic clamps, n = 43. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Pancreatic insulin secretion in response to hyperglycemia and insulin action as assessed by insulin-mediated glucose utilization using the euglycemic, hyperinsulinemic clamp technique. RESULTS: We identified no significant correlation between serum androgens and either glucose uptake or insulin-mediated glucose utilization. Glucose-stimulated insulin release was negatively correlated with serum T and free T throughout the normal range of these hormones. CONCLUSION: We conclude that, within the normal range, variations of serum androgens are not correlated with changes in the response to insulin. It seems unlikely, therefore, that modest increases of serum androgens within the normal range are responsible for inducing insulin resistance. PMID- 1459258 TI - Effect of hyperprolactinemia on the androgen response to an oral glucose load. AB - OBJECTIVE: To investigate the effect of hyperprolactinemia on the androgen response to an oral glucose load in patients with normal and abnormal carbohydrate metabolism. DESIGN: Sixty-three women underwent a 75-g oral glucose tolerance test (OGTT) at approximately 6 weeks' postpartum. SETTING: University hospital setting. PATIENTS: Patients with a previous history of gestational diabetes. MAIN OUTCOME MEASURE: Adrenal and ovarian androgen response to oral glucose load. RESULTS: Results were stratified by the result of the OGTT (patients with impaired glucose tolerance or diabetes as a single group and patients with a normal OGTT as a separate group) and prolactin (PRL) level. All androgens decreased significantly over the 2-hour test in all groups except dehydroepiandrosterone sulfate (DHEAS) in the patients with both elevated PRL and abnormal glucose tolerance. CONCLUSION: Hyperprolactinemia and insulin resistance may act synergistically in the adrenal to alter DHEAS suppression and may result in chronically elevated circulating DHEAS levels. PMID- 1459259 TI - Interinstitutional variability of follicle-stimulating hormone and estradiol levels. AB - OBJECTIVE: To evaluate the variability of follicle stimulating hormone (FSH) and estradiol (E2) results from different laboratories. DESIGN: Prospective analyses of sera separated and frozen, obtained from 15 female patients in the follicular phase. All kits used for radioimmunoassay (RIA) for FSH were from the Second International Reference Preparation (IRP). Four different kits were used for FSH and three for E2. SETTING: Sera obtained from each patient were separated into five test tubes and frozen. Analysis of all samples was done on the same day in each one of five participating hospital-based RIA laboratories (North Shore, Cornell, Yale, Mount Sinai, and Norfolk). PARTICIPANTS: Fifteen consecutive patients from the assisted reproductive technology program at North Shore University Hospital participated in the study. MAIN OUTCOME MEASURES: After FSH and E2 levels were tabulated for each laboratory, mean levels were calculated. RESULTS: Using the Bonferroni adjusted pairwise multiple comparisons analysis, significant differences were found between three groups of laboratories within the FSH results and three different groups within the E2 results. CONCLUSIONS: [1] Different results may be obtained on the same sera for FSH and E2 at different laboratories; [2] for FSH, even though the same IRP is used, different results are reached; [3] for E2, even when the same kits are used, results may be significantly different. These results suggest that specific FSH and E2 levels used to predict chances for achieving a viable pregnancy through in vitro fertilization should be interpreted with caution across institutions. PMID- 1459260 TI - Endometrial dating in the conception cycle. AB - OBJECTIVE: To investigate endometrial dating during the conception cycle. DESIGN: Endometrial biopsies of the last half of the luteal phase of conception cycles were dated based on urinary luteinizing hormone (LH) surges. SETTING: Endometrial samples were obtained from women attending the fertility clinic of the Department of Obstetrics and Gynecology at Gunma University Hospital. PATIENTS: One hundred eighty-five women, of whom 15 (8.1%) conceived during this study. MAIN OUTCOME MEASURES: Urinary LH surge, serum progesterone (P) levels, and endometrial dating. RESULTS: All 10 women who conceived showed 2 or within 2 days in-phase endometrial biopsies on days 7 to 11 after the LH surge. In 4 of 5 women biopsied on day 12, an unequivocally delay in the stroma was found, i.e., a persistence of edema and poor development of predecidual reaction. Since serum P levels in conception cycles were significantly higher than in nonconception cycles on days 10, 11, and 12, we interpreted this delay in the stroma as a consequence of conception. CONCLUSION: Endometrial specimens during the last half of the luteal phase of conception cycles are in-phase until day 12. On day 12, gestational hyperplasia causes apparent out-of-phase. PMID- 1459261 TI - Transcervical cannulation of the fallopian tube for the management of ectopic pregnancy: prospective multicenter study. AB - OBJECTIVE: To determine the efficacy of transcervical tubal cannulation and intraluminal methotrexate injection for the management of tubal ectopic pregnancy (EP). DESIGN: Prospective multicenter study of 33 patients with tubal pregnancies. SETTING: Four university-based gynecology and radiology departments in three different countries: France, England, and Germany. PATIENTS: Thirty three patients who presented with a clinical diagnosis of EP. INTERVENTIONS: Patients underwent transcervical tubal cannulation under fluoroscopic or ultrasound control and local injection of methotrexate (up to 50 mg). MAIN OUTCOME MEASURES: We evaluate the feasibility of transcervical tubal cannulation for the management of tubal pregnancy. RESULTS: Two patients elected to withdraw from the protocol. In the remaining 31 patients there was complete resolution of the EP in 27 (87%). Surgery was performed in 4 patients. Seventeen patients, 14 of whom desired pregnancies, were available for follow-up to assess the return of reproductive potential. Seven of 7 patients who subsequently underwent hysterosalpingography had patency of the affected tube. Five patients later had an intrauterine pregnancy. One patient had an early miscarriage, two have given birth, and two singleton pregnancies are still ongoing. The remaining patients are symptom free. CONCLUSIONS: This study demonstrates that transcervical tubal catheterization in patients with tubal pregnancies is feasible and can be performed without anesthesia or analgesia in most cases. Intraluminal methotrexate per se is capable of causing regression of the EP. This approach offers a new alternative for the treatment of selected patients with tubal EP. PMID- 1459262 TI - Standardization of hysterosalpingography and selective salpingography: a valuable adjunct to simple opacification studies. AB - OBJECTIVE: To investigate the correlation between opacification and perfusion pressures during hysterosalpingography (HSG) and selective salpingography under the assumption that the latter may add to the diagnostic capabilities of the procedures. DESIGN: Perfusion pressures were uniformly evaluated by standardizing injection volume per time interval of contrast medium and the delivery system. Pressures were measured in a closed system through a digital manometer and recorded on tracing paper. SETTING: Fully ambulatory gynecoradiology suite at academically affiliated infertility center. PATIENTS: Thirty infertility patients. INTERVENTION: Hysterosalpingography and selective salpingography for diagnostic purposes. MAIN OUTCOME MEASURE: Correlation between opacification patterns and perfusion pressures. RESULTS: The evaluation of perfusion pressures during HSG is unreliable because they may be affected by uterine factors and will only reflect the oviduct of least resistance. In contrast, perfusion pressures during selective salpingography are reflective of only the investigated tube. They appear to lie within a functionally normal range of up to 350 mm Hg. Tubes by opacification judged as normal exhibited a pressure range of 429 +/- 376 mm Hg, which was significantly lower than that of abnormally appearing oviducts (957 +/- 445 mm Hg; P = 0.001). CONCLUSIONS: The concomitant performance of perfusion pressure studies during selective salpingography further enhances the diagnostic capability of selective salpingography over HSG in the diagnostic evaluation of fallopian tubes. PMID- 1459263 TI - A contraceptive subdermal implant releasing the progestin ST-1435: ovarian function, bleeding patterns, and side effects. AB - OBJECTIVE: To study ovarian function, bleeding patterns, and side effects during the 1-year use of a new modified contraceptive subdermal implant releasing the progestin ST-1435 with a lifetime of 2 years. DESIGN, PATIENTS: The effect on ovarian function and bleeding patterns of one contraceptive implant releasing the progestin ST-1435 was studied in 26 healthy women who volunteered. Side effects were recorded. SETTING: The outpatient clinic of the City Maternity Hospital, Helsinki, Finland. INTERVENTION: One ST-1435 contraceptive implant was inserted subcutaneously into the ventral aspect of left upper arm. MAIN OUTCOME MEASURES: The women attended the clinic at half-year intervals. Records of bleeding were kept. Blood samples were collected from 5 women before insertion of an implant, from 12 women during the first 5 to 6 weeks of use, and from 10 women during the 6th and 12th month of use. Serum concentrations of ST-1435, progesterone, and estradiol were determined. Side effects were reported. RESULTS: The study covered 302 woman-months. The implant gave serum concentrations of ST-1435 high enough to inhibit ovulation in all of the 37 analyzed cycles. No pregnancies occurred. Irregular bleeding or spotting was the main event observed, especially during the 1st year of use. One half of the users had irregular cycles. None of the women's implants was removed during 1 year of use because of irregular bleeding. The implant was well accepted and tolerated by the women; no hormonal side effects were reported. CONCLUSIONS: One single 4-cm subdermal ST-1435 implant with a lifetime of 2 years showed good contraceptive efficacy and led to suppression of ovulation. No hormonal side effects were reported. Irregular bleeding patterns were common but well-tolerated, and the implant had a high continuation rate. PMID- 1459264 TI - In vitro lymphocyte activity in women with endometriosis--an altered immune response? AB - OBJECTIVE: To determine the possible role of the immune system in the pathogenesis of endometriosis. DESIGN: The lymphocyte proliferative response in the presence of autologous endometrial cells was assayed by tritiated thymidine incorporation. SETTING: Patients were recruited from a university outpatient clinic. MAIN OUTCOME MEASURE: To determine the lymphocyte proliferative response to endometrium in controls and patients with endometriosis. PARTICIPANTS: Twenty patients with endometriosis and 26 control women were studied. RESULTS: The lymphocyte proliferative response in the presence of autologous endometrium was significantly lower in women with endometriosis when compared with controls. CONCLUSION: This study indicates that an altered lymphocyte/endometrial cell relationship is operational in women with endometriosis and may contribute to the pathogenesis of the disease. PMID- 1459265 TI - Steroidogenesis of cultured granulosa cells in women at risk for ovarian hyperstimulation syndrome. AB - OBJECTIVE: To determine if cultured human granulosa cells (GCs) obtained from women at risk for ovarian hyperstimulation syndrome (OHSS) possess altered steroidogenic capacity. DESIGN: Prospective analysis of 28 consecutive in vitro fertilization-gamete intrafallopian transfer (IVF-GIFT) cycles. SETTING: In Vitro Fertilization Program at Rush Presbyterian St. Luke's Medical Center in Chicago, Illinois. PATIENTS: Eighteen patients (group I) with serum estradiol (E2) levels > 7,342 pmol/L on the day of exogenous human chorionic gonadotropin (hCG) administration (day 0) with > 10 ovarian follicles present (high risk for OHSS); 10 patients (group II) with E2 < or = 7,342 pmol/L on day 0 and < or = 10 follicles. INTERVENTIONS: Human GCs obtained during gonadotropin-releasing hormone agonist-pretreated IVF-GIFT cycles were cultured in the absence (control) or presence (hCG) of hCG, 1 IU/mL, and/or androstenedione (A) 10(-7) M. Granulosa cells obtained from follicles < or = 15 mm diameter were cultured separately from those obtained from follicles > 15 mm diameter. MAIN OUTCOME MEASURES: Estradiol (E2) and progesterone were measured in tissue-culture medium by a solid-phase direct radioimmunoassay. RESULTS: In vitro E2 production by cultured GCs was significantly increased in follicles < or = 15 mm diameter from women considered at risk of developing OHSS (group I). Estradiol response to hCG and/or A appeared enhanced in all follicles in group I. Progesterone production in the basal and hCG challenged state was greater in cells obtained from large follicles in group I than in group II. CONCLUSION: Ovarian hyperstimulation syndrome appears to be a function of an increased number of follicles that express an enhanced steroidogenic capacity. PMID- 1459266 TI - The prevalence and predictability of depression in infertile women. AB - OBJECTIVE: To determine the prevalence, severity, and predictability of depression in infertile women compared with a control sample of healthy women. DESIGN: Subjects were assessed while waiting to see their physician: infertility patients before a visit with an infertility specialist and control subjects before seeing either a gynecologist or internist for a routine gynecological examination. Subjects completed a demographic form and two depression scales. SETTING: A group infertility practice affiliated with an academic medical center, a hospital-based gynecology practice, and a health maintenance organization internal medicine clinic. PARTICIPANTS: 338 infertile women and 39 healthy women. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The Beck Depression Inventory and the Center for Epidemiological Studies Depression Scale. RESULTS: The infertile women had significantly higher depression scores and twice the prevalence of depression than the controls; women with a 2- to 3-year history of infertility had significantly higher depression scores compared with women with infertility durations of < 1 year or > 6 years; women with an identified causative factor for their infertility had significantly higher depression scores than women with unexplained or undiagnosed infertility. CONCLUSIONS: Depressive symptoms are common in infertile women. Psychological interventions aimed at reducing depressive symptoms need to be implemented, especially for women with a definitive diagnosis and for those with durations of 2 to 3 years of infertility. PMID- 1459267 TI - Ultrashort gonadotropin-releasing hormone agonist (GnRH-a) protocol in comparison with the long-acting GnRH-a protocol and menotropin alone. AB - OBJECTIVE: To compare the in vitro fertilization and embryo transfer (IVF-ET) outcome of a 3-day gonadotropin-releasing hormone agonist (GnRH-a) administration: ultrashort protocol with the outcome of long-acting GnRH-a cycles or human menopausal gonadotropin (hMG) alone. DESIGN: Ninety-two cycles of the ultrashort protocol were matched with 92 cycles with long GnRH-a and with 92 hMG cycles. SETTING: The IVF-ET program. MAIN OUTCOME MEASURES: Amount and duration of hMG treatment, hormonal profile on the day of human chorionic gonadotropin administration, cancellation rate, number of oocytes retrieved, and fertilization and pregnancy rates (PRs) were examined and compared among the three groups. RESULTS: The ultrashort group needed a higher number of hMG ampules than the hMG group but significantly less than in the long GnRH-a regimen. The number of oocytes in the ultrashort protocol was the same as in the long GnRH-a, but the number of embryos per retrieval was significantly lower than with the long GnRH-a protocol and similar to that found in the hMG group. The ultrashort protocol yielded 10% PR per cycle and 17% per replacement, significantly lower than with the long GnRH-a protocol, 26% and 36%, respectively, but also lower than in the hMG one, namely 13% and 28%. CONCLUSION: The ultrashort protocol, although being convenient and having some advantages found in the long GnRH-a protocol, is inferior in its outcome compared with the two other protocols. PMID- 1459268 TI - Prospective study of short and ultrashort regimens of gonadotropin-releasing hormone agonist in an in vitro fertilization program. AB - OBJECTIVE: To assess the usefulness of the ultrashort regimen of gonadotropin releasing hormone agonist (GnRH-a) in ovulation induction in an in vitro fertilization (IVF) program. DESIGN: A prospective randomized trial comparing short and ultrashort regimens of GnRH-a. SETTING: Aberdeen Assisted Reproduction Unit. PATIENTS: Forty-eight patients having IVF for the first time were randomized between the two protocols. MAIN OUTCOME MEASURES: Response to ovarian stimulation and occurrence of spontaneous luteinizing hormone (LH) surges. RESULTS: In ovulation induction, fertilization, and pregnancy rates the ultrashort regimen produces results that were no different to the short regimen but it did not always prevent an LH surge. CONCLUSION: The ultrashort regimen can be a useful alternative for ovarian stimulation of patients undergoing IVF. PMID- 1459269 TI - Influence of ovarian cysts on the results of in vitro fertilization. AB - OBJECTIVE: To determine if ovarian cysts are associated with a particular basal endocrine profile and impair follicular growth. DESIGN: Retrospective study. SETTING: In Vitro Fertilization (IVF) Center. PATIENTS: Nine hundred fourteen stimulation cycles stimulated with a combination of luteinizing hormone-releasing hormone analogues (LH-RH-a) and human menopausal gonadotropins (hMG) in a long protocol in an IVF program. RESULTS: After 15 days of LH-RH-a therapy, ovarian cysts (> or = 20 mm) were observed in 8% of cases. These cysts were not related to a particular basal endocrine profile and did not impair follicular growth and IVF results. However, puncturing these cysts enhanced the quality of subsequent follicular growth. On the contrary, cysts appearing during hMG treatment (> or = 25 mm) were related with a lower LH:follicle-stimulating hormone ratio (0.79 +/- 0.52 versus 0.92 +/- 0.74 in absence of cyst) and to a lower ovarian response as assessed by the maximal estradiol level to the total number of hMG ampules ratio (51.6 +/- 36.5 versus 65.9 +/- 47.9 in absence of cyst). However, this difference had no influence on the pregnancy per stimulation rate (18% versus 16% in absence of cyst; not significant). CONCLUSIONS: Results show that the pathogens of ovarian cysts appearing during the blockage phase and during the stimulation phase are different. However, they do not impair the results of IVF, and thus it is not necessary to cancel the attempt in case of ovarian cyst. PMID- 1459270 TI - Direct effects of progesterone and antiprogesterone on human sperm hyperactivated motility and acrosome reaction. AB - OBJECTIVE: To study the direct effects of progesterone (P) and its antagonist RU486 (mifepristone) on sperm hyperactivation (HA) and acrosome reaction. DESIGN: Prospective evaluation of semen samples incubated in capacitation media with P and/or RU486. SETTING: University-affiliated tertiary care center. PATIENTS: Normal healthy volunteers. INTERVENTIONS: Semen samples were incubated in media with P or RU486 alone or in combination, and aliquots were taken at 10 minutes, 1, 5, and 24 hours for HA analyses by computer-aided sperm analysis system, and at 0, 5, and 24 hours for assessment of acrosome reaction by fluorescein-labeled Pisum sativum (pea) agglutinin. MAIN OUTCOME MEASURES: HA and acrosome reaction. RESULTS: Sperm HA was significantly increased at 10 minutes by P both at 10(-7) M (9.27 +/- 1.59%; mean +/- SEM) and 10(-6) M (9.39 +/- 1.94%) when compared with untreated spermatozoa (5.62 +/- 1.59%). The stimulatory effect of P on sperm HA was transient because this was not observed after 1, 5, and 24 hours of incubation. The antiprogesterone RU486 (10(-6) M) alone had no effect and did not abolish the stimulatory effect of P on HA. The %HA was further enhanced by the addition of RU486 at 10(-6) M to P at 10(-7) M (12.43 +/- 3.31%) or P at 10(-6) M (13.52 +/- 4.10%); however, this effect was not significantly different from P alone. Coincubation of P or RU486 with spermatozoa during capacitation did not stimulate the acrosome reaction in the concentrations tested. CONCLUSION: Progesterone directly stimulates human sperm HA transiently. Progesterone has no significant effect on acrosome reaction in capacitating spermatozoa. The effects of P are rapid and not counteracted by RU486, suggesting that the mechanism of action of P may not be mediated by specific P nuclear receptors. PMID- 1459271 TI - Correlation between puberty and the development of autoimmunity to spermatozoa in men with cystic fibrosis. AB - OBJECTIVE: To test the hypothesis that puberty is a necessary factor in the pathogenesis of autoimmunity to sperm in men with cystic fibrosis (CF), we studied prepubertal and postpubertal males with CF versus an age-matched group of males with type 1 diabetes as controls. DESIGN: Sera from CF and diabetic males treated at University Hospital, State University of New York, Stony Brook, were tested by indirect immunobead binding for antisperm antibodies and by radioimmunoassay for testosterone (T), luteinizing hormone, and follicle stimulating hormone. The finding of autoantibodies to spermatozoa was correlated with chronological age, as well as with clinical and hormonal pubertal status. RESULTS: Autoimmunity to sperm, as detected by humoral antisperm antibodies, was documented solely in postpubertal males, as judged by hormonal and clinical criteria. Eighty-three percent of sexually mature CF males and 6.3% (1 of 16) diabetic males exhibited autoantibodies to sperm. These antibodies were only detected when serum T levels were > 8.7 nmol/L (250 ng/dL). CONCLUSIONS: These results suggest that puberty, and presumably, active spermatogenesis is a requirement for the development of autoimmunity to sperm in men with CF. PMID- 1459272 TI - Enhanced gamete interaction in the sperm penetration assay after coincubation with pentoxifylline and human follicular fluid. AB - OBJECTIVE: To evaluate the effect of pentoxifylline and heat-inactivated human follicular fluid (FF) on performance in the sperm penetration assay (SPA) as a paradigm for the effect of these agents on human sperm-egg interaction in vivo and in vitro fertilization. DESIGN: Semen specimens from men undergoing SPA testing for evaluation of suspected male factor infertility were coincubated with neat medium or media supplemented with pentoxifylline or human FF in a nonblinded manner. PARTICIPANTS: Twenty male factor infertility patients. INTERVENTIONS: Semen specimens were preincubated with: [1] pentoxifylline 0.25 mg/mL; [2] 10% human FF; [3] pentoxifylline+human FF; and [4] neat Biggers, Whitten, and Whittingham medium. MAIN OUTCOME MEASURES: Differences in the rate of penetration of zona-free hamster oocytes. RESULTS: Preincubation with either human FF or pentoxifylline produced a significant improvement in hamster egg penetration rates. Coincubation with a combination of human FF and pentoxifylline resulted in a significant enhancement of penetration as compared with single agent treatment. CONCLUSIONS: Coincubation of sperm with human FF and pentoxifylline may provide a means of enhancing sperm activity for insemination and assisted reproduction. PMID- 1459273 TI - Interval required for gonadotropin-releasing hormone-agonist-induced down regulation of the pituitary in cynomolgus monkeys and duration of the refractory state. AB - OBJECTIVES: To determine the minimal interval of gonadotropin-releasing hormone agonist (GnRH-a) administration required to induce pituitary refractoriness to the positive feedback effects of estradiol (E2) and to determine the duration of the induced refractory state in a nonhuman primate model. SETTING: Research laboratories of The Jones Institute for Reproductive Medicine. SUBJECTS: Cynomolgus monkeys with documented regular menstrual cycles. INTERVENTIONS: Part 1. Groups of four monkeys treated with leuprolide acetate (LA) for increasing intervals (0, 2, 4, 6, and 8 days), then challenged with E2 benzoate to induce a gonadotropin surge. Part 2. Groups of four monkeys treated with LA for the minimal time required to induce pituitary refractoriness (6 days), then challenged with E2 benzoate 2, 4, or 7 days after cessation of LA treatment. MAIN OUTCOME MEASURE(S): Pituitary luteinizing hormone and follicle-stimulating hormone and E2 levels were monitored. RESULTS: A minimum of 5 days of treatment is required for LA to induce pituitary refractoriness to the positive feedback effects of E2 benzoate. Once the down regulated condition is achieved, the refractory state lasts for at least 4 but not more than 6 days. CONCLUSION: The minimal treatment interval required for a GnRH-a to induce pituitary refractoriness to the positive feedback effects of estrogen and the duration of the induced refractory state are determined to be 5 days for these primates. PMID- 1459274 TI - Experimentally induced endometriosis in rats: effect on fertility and the effects of pregnancy and lactation on the ectopic endometrial tissue. AB - OBJECTIVE: To investigate the repercussion of experimentally induced endometriosis on the fertility of Wistar rats and the effects of pregnancy and lactation on endometrial ectopic implants. DESIGN: Eight-five animals were used for the experiment. Experimental endometriosis was induced in 44 and the remaining 41 were sham-operated (control group). After evaluating the growth of the implants in a second laparotomy, all the animals were mated until finding sperm in vaginal smears. In third and fourth laparotomies during pregnancy and lactation, pregnancy rate was determined, and the implants were re-evaluated, being resected for histological study. Serum estradiol (E2) and progesterone (P) levels were also measured. RESULTS: The pregnancy rate in animals with endometriosis was 65.7% versus 100% in control group. No statistical differences in days of gestation and number of pups were found between the two groups. Ectopic implants underwent a significant regression during lactation period. Serum E2 and P levels and histological features sustained these findings. CONCLUSION: Experimentally induced endometriosis diminishes pregnancy rate in rats. It is not pregnancy, but the anestrus condition created by lactation that exerts a beneficial effect on experimentally induced endometriosis in rats. PMID- 1459275 TI - Proliferative and morphogenic changes induced by the coculture of rat uterine and peritoneal cells: a cell culture model for endometriosis. AB - OBJECTIVE: To evaluate the proliferative and morphogenic effects induced by the coculture of uterine and peritoneal cells to establish a cell culture model for endometriosis. DESIGN: Uterine epithelial and stromal cells and peritoneal mesothelial and subserosal cells were cocultured with homologous cell types, heterologous cell types, or as isolated populations using a bicameral chamber design. SETTING: Department of Obstetrics and Gynecology at the University of Missouri, Columbia, Missouri. ANIMALS: Cells isolated and purified from five mature female Sprague Dawley rats of normal reproductive status were used to establish cell cultures. MAIN OUTCOME MEASURES: Cell proliferation (deoxyribonucleic acid synthesis) was measured by the incorporation of 3H thymidine, and cell morphology was assessed using inverted phase-contrast microscopy. RESULTS: Peritoneal mesothelial cells augmented proliferation and induced cellular aggregation of uterine stromal cell monolayers. Peritoneal subserosal cells amplified proliferation and induced an irregular, compacted morphology in uterine epithelial cells. The proliferation and morphology of the two peritoneal cell types was not altered by uterine cell coculture. CONCLUSIONS: The coculture of uterine and peritoneal cells in bicameral chambers provides a tool to study the paracrine interactions of cells that comprise the endometriotic lesion. The altered proliferation and morphology of the uterine cells may be related to the histologic and biochemical asynchrony observed between uterine endometrium and ectopic endometriotic tissue in vivo and offers insight into possible mechanisms of the histogenesis of endometriosis. PMID- 1459276 TI - The menstrual cycle: relations of biophysical and hormonal determinations in normal women of reproductive age. AB - Appropriate relationships between circulating levels of 17 beta-E2 and P are necessary for normal endometrial development and blastocyst implantation. The aim of this study was to relate biophysical and biochemical measurements obtained during the menstrual cycle of six healthy women in 25 menstrual cycles. One hundred eighteen vaginosonographic determinations of the endometrial thickness together with serum E2 and P assays were performed at 5-day intervals. The three parameters studied were standardized by the formula: observation minus mean determination for that parameter divided by the standard deviation of that parameter. Using this common unit, the physiological relations between ultrasonographically determined endometrial thickness, E2, and P were readily seen. PMID- 1459277 TI - The role of office hysteroscopy in in vitro fertilization. AB - Twenty-eight patients participated prospectively in a study to evaluate the impact of hysteroscopically detected uterine and cervical anomalies on the success rate of ET in an IVF-ET program. All participants had a normal intrauterine cavity by standard HSG. All the patients had a diagnostic office hysteroscopy under paracervical block before commencing COH. Because our IVF program does not include hysteroscopy as a requirement before undergoing IVF and because the significance of mild intrauterine abnormalities is not yet known, the hysteroscopic findings were not relayed to the personnel involved in the IVF-ET procedure. Sixteen patients (group I) had a normal hysteroscopic evaluation. Twelve patients (group II) had abnormal hysteroscopic findings including small uterine septa, small submucous fibroids, uterine hypoplasia and cervical ridges. Although no difference in patients or cycle characteristics was present, there was a significant difference in the clinical PR between patients in groups I and II. In conclusion, in an IVF-ET program patients with normal hysterography but abnormal hysteroscopic findings had a significantly lower clinical PR, demonstrating the importance of performing hysteroscopy before IVF-ET. PMID- 1459278 TI - Local anesthesia with conscious sedation for laparoscopic intrafallopian transfer. AB - Local anesthesia with conscious sedation is well accepted by patients and provides scheduling flexibility, cost containment, patient safety, and ease of recovery. We believe the technique should be offered to selected patients undergoing intrafallopian transfer. By adhering to specific guidelines for surgical technique and monitoring, the procedure is a safe and acceptable alternative to general anesthesia for laparoscopic intrafallopian transfers. PMID- 1459279 TI - Method for the transportation of peritoneal macrophages. AB - This report outlines a method of PF transport that preserves the viability and activation level of peritoneal macrophages. Collection of macrophages in this manner will allow transport of PF from multiple centers for evaluation of macrophage function in a single laboratory. Such technology will make it possible to intensively study the relationship between peritoneal macrophages and infertility. PMID- 1459280 TI - Chlamydia antibody by enzyme-linked immunosorbent assay and associated severity of tubal factor infertility. AB - We have evaluated the clinical utility of the serum chlamydial antibody value by ELISA in predicting the severity of tubal factor infertility quantified by the use of a previously reported pelvic scoring system. Significant differences in salpingitis scores, tubal occlusion scores, adhesion scores, and pelvic stages were found with increasing chlamydia antibody grades. The level of ELISA value strongly correlated with salpingitis, tubal occlusion, and total pelvic scores and pelvic stages. The serum chlamydia antibody level by ELISA now appears to be a useful prognostic tool for predicting the severity of tubal factor infertility in addition to its value in screening for its presence. PMID- 1459281 TI - Umbilical metastases from a stage IB cervical cancer after laparoscopy: a case report. AB - The first reported case of laparoscopy site metastases from an unsuspected stage IB cervical cancer diagnosed during laparoscopy for endometriosis is presented. Implications of this clinical situation are discussed. PMID- 1459282 TI - Fresh and frozen-thawed human sperm bind in a similar pattern to the zona pellucida in the hemizona assay. AB - This study evaluated the impact of sperm cryopreservation on sperm quality. The HZA was used to test the binding capacity of fresh as opposed to frozen-thawed sperm from 12 donors. Fresh and frozen-thawed sperm motility was 47% +/- 1.5% and 24% +/- 3.8% (mean +/- SE), respectively. However, the number of sperm cells attached to the hemizonae was 75 +/- 12.0 and 74 +/- 11.9, respectively. We conclude that cryopreservation results in a reduced number of motile sperm cells but does not adversely affect the ability of rescued sperm cells to bind to the ZP. The study also supports the use of frozen-thawed rather than fresh donor sperm for control in the HZA procedure. PMID- 1459283 TI - Round cells and sperm fertilizing capacity: the presence of immature germ cells but not seminal leukocytes are associated with reduced success of in vitro fertilization. AB - Fifty semen samples produced for IVF by patients diagnosed as having unexplained infertility were screened for leukocytes, leukocyte subsets, and immature germ cells using a mAB-based staining procedure. Nonfertilizing ejaculates were found to contain significantly larger numbers of immature germ cells, although no significant differences in leukocyte content were observed between groups. Neither sperm density or progressive motility were significantly different between fertilizing and nonfertilizing groups. We conclude that seminal leukocytes have little if any influence on the fertilizing capacity of the spermatozoa in patients undergoing IVF for unexplained infertility, but the presence of large numbers of germinal elements is associated with reduced fertilizing capacity and may be indicative of an immature sperm population. PMID- 1459284 TI - Laparoscopic internal spermatic vein ligation: report of a new technique. AB - Over the past 22 months, 51 laparoscopic internal vein ligations have been performed to determine its application and practicality in treating the infertile male with varicoceles. Of the 33 cases available for a follow-up of greater than 6 months, 16 pregnancies are reported. Five patients reporting pregnancies refused to submit a postoperative semenogram. Of the reportable series, 17 of 33 had significant improvement in sperm density (51%), 15 of 33 (45%) in sperm viability, and 15 of 33 (45%) in sperm motility. No major complications were seen and minor complications were few and transient. Morbidity was extremely low. Laparoscopic internal spermatic vein ligations would appear to be a reasonable, practical, and effective method to correct varicoceles. PMID- 1459285 TI - New technique for ovulation induction--transvaginal follicular aspiration? PMID- 1459286 TI - Pharmacokinetics of intratubal methotrexate. PMID- 1459287 TI - Oral contraceptives and breast cancer. PMID- 1459288 TI - Oral contraceptives and breast cancer. PMID- 1459289 TI - Levitating human sperm--an Adman's dream. PMID- 1459290 TI - Levitating human sperm--an Adman's dream. PMID- 1459291 TI - [Did growth hormone-deficient children grow up to normal adult height by growth hormone treatment?]. AB - One of the important aims of growth hormone (GH) treatment in GH deficient children is to allow them to grow to their full genetic potential. Usually, however, the final height of GH deficient children does not reach normal adult height and is below their target height. Furthermore, isolated GHD with spontaneous puberty is known to lead to a shorter adult height than that obtained in GHD associated with gonadotropin deficiency. The height at the start of puberty is reported to be well correlated with final height in GHD. Therefore, when isolated GHD subjects treated with GH reached puberty while they were still shorter than normal, they ended up by being shorter than normal as adults. The trial to increase the GH dose during puberty did not seem to increase the final height. The gonadal suppression therapy combined with GH treatment significantly increased the final height in isolated GHD. It is now the consensus that insufficient height at the onset of puberty leads to short final height and that early diagnosis of GHD is thus important to allow catch-up growth to optimal height before puberty. It may also be beneficial to treat GHD with higher doses to overcome the waning phenomenon with GH treatment. PMID- 1459292 TI - [Difference of acute ketone body metabolism between insulin-dependent diabetic and non-insulin-dependent diabetic individuals]. AB - The difference in the acute metabolic change in ketone bodies between patients with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) was investigated in this study. The subjects employed were 7 patients with IDDM losing residual insulin secretion and 7 patients with NIDDM matched to the former patients for age, body mass index, duration of diabetes, daily insulin dosage, fasting plasma glucose and HbA1c. Blood samples were drawn at 3A.M. and 7A.M. on the same day, and plasma glucose, acetoacetic acid (AcAc), 3-beta-hydroxybutylic acid (3-OHBA), free fatty acid (FFA), glycerol, cortisol and growth hormone (GH) concentrations were determined. Plasma total ketone bodies (AcAc and 3-OHBA), 3-OHBA and FFA concentrations at 7A.M. were significantly higher in the patients with IDDM than in those with NIDDM (p < 0.05), while there were no significant differences in any other parameters at 3A.M. between the patients with IDDM and those with NIDDM. The ratios of 7A.M. value/3A.M. value of total ketone bodies, AcAc and 3-OHBA concentrations were also more significantly elevated in the patients with IDDM than in those with NIDDM. It was observed that the ratio of 3-OHBA was more than 2.0 in all of the patients with IDDM and less than 2.0 in all of the patients with NIDDM, the difference being significant with p < 0.001.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459293 TI - [Pregnancy in Cushing's syndrome]. AB - Pregnancy in cases of Cushing's syndrome is rare. A pregnant patient with Cushing's syndrome due to an adrenal adenoma who was diagnosed in the third trimester is described. She underwent conservative treatment for Cushing's syndrome and delivered a normal infant by Caesarean section. Currently, 121 pregnancies in 97 patients have been reported, but a principle for the treatment of the mother and fetus has not yet been established. We reviewed pregnancy in Cushing's syndrome based on the world literature and evaluated the choice of treatment to take. In the first trimester of pregnancy, therapeutic abortion or surgical treatment, such as adrenalectomy or resection of the pituitary tumor in Cushing's syndrome, is recommended for patients with severe hypercorticism (plasma cortisol > or = 30 micrograms/dl, urinary 17-OHCS > or = 15 mg/day, urinary free cortisol > or = 1000 micrograms/day), while conservative treatment is recommended for patients with mild hypercorticism (plasma cortisol < 30 micrograms/dl, urinary 17-OHCS < 15 mg/day, urinary free cortisol < 1000 micrograms/day). In the second trimester of pregnancy, surgical treatment is recommended for patients with severe hypercorticism, while conservative treatment is recommended for patients with mild hypercorticism. In the third trimester of pregnancy, Caesarean section is recommended for most cases. Drug treatments such as with metyrapone should be limited to patients showing severe hypercorticism or a maternal high risk who have contraindications to surgical treatment. PMID- 1459294 TI - Epidemic of malaria in Barmer district (Thar desert) of Rajasthan during 1990. AB - Barmer district of Rajasthan in Thar desert and hitherto a hypoendemic area for malaria came in the grip of a severe malaria epidemic during 1990. The epidemic occurred as an aftermath of floods, preceded by normal rains during 1988 and 1989 after a prolonged drought phase. The epidemic was spread over the whole district including Barmer town. Annual Parasite Incidence (API) and Annual falciparum Incidence (AFI) for the district touched record figures of 17.20 and 5.83 respectively while for the Barmer town they were 36.5 and 14.0 respectively. Out of the eight PHCs, Baitu PHC was the worst affected where the two indices touched all-time high figures of 55.3 and 19.6 per cent respectively. A total of 122 infants were reported positive for malaria, of which 103 were contributed by Baitu PHC alone. Eighty per cent infant positivity was spread over September and November, indicating a high rate of transmission. A total of 47 deaths due to cerebral malaria were reported. However, in view of the high infectivity among infants and paediatric groups there was a strong possibility of deaths among these groups which could not be verified. Entomological findings revealed that a sudden increase in An. culicifacies densities due to extensive breeding potential, as a sequel to floods, activated the transmission, which was maintained at a low level by An. stephensi, predominant in this desert region. Other factors which contributed to the intensity and extent of epidemic were the return of drought-migrated population from malarious areas, low cattle density, malaria non-immune population, inadequate and poor spray coverage and delayed radical treatment. Insecticide adult susceptibility tests revealed a high degree of resistance in An. stephensi against DDT and dieldrin. PMID- 1459295 TI - Gujarat model of health management information system with reference to malaria. AB - The Gujarat model of health management and information system has been developed with the objective of reducing the work load of health workers at all levels pertaining to record keeping and report preparation for enhancing the quality of health services, as well as for better implementation and timely monitoring of health programmes. Pro formas currently in use under various health programmes have been reorganized and updated. For monitoring malaria, the total number of registers has been reduced from seven to one, reporting forms from 23 to six and the number of columns in reporting forms from 493 to 59. The model is expected to save the working time of laboratory technicians (15%) and multi-purpose health supervisors (5%) at PHC level and of all workers (100%) engaged in report preparation at district, state and national levels. The data generated by using this model are expected to be of high quality and accuracy and should lead to more rational planning. PMID- 1459296 TI - Antigenic diversity amongst ten geographic isolates of Plasmodium falciparum defined by merozoite invasion inhibition assay. AB - The extent to which human antibodies involved in functional immunity react with antigenic determinants varying between different isolates or strains of human malaria parasite Plasmodium falciparum will influence the design of vaccine against malaria. In this study, in vitro inhibition of merozoite invasion in erythrocytes by an immune human serum was used to define the antigenic differences in 10 isolates of P. falciparum from three endemic areas, i.e. Africa, South America and Southeast Asia. The serum inhibited the invasion of merozoites of all the strains but the extent of inhibition varied from low to moderate to high degree indicating antigenic differences amongst isolates of P. falciparum. The antigenic differences could not be correlated to the geographic origin of the parasite isolate. PMID- 1459297 TI - Observations on malaria patients seeking treatment in hospitals in a rural and an urban area of Sri Lanka. AB - Malaria in Sri Lanka is endemic in the dry zone and occurs during epidemics in the wet zone. A survey was carried out on malaria patients presenting at a hospital located in a predominantly rural area in the dry zone (Polonnaruwa) and an urban area in the wet zone (Ragama). Higher incidence of Plasmodium falciparum infections than reported nationally were observed in both locations. Of particular interest is the rapidity with which patients gained access to hospital treatment after the onset of malaria symptoms. The observed mode is 3-6 days. It is postulated that early treatment may impair the development of clinical immunity to malaria in the Sri Lankan population. PMID- 1459298 TI - Breeding habitats and their contribution to Anopheles stephensi in Panaji. AB - A one-year longitudinal study conducted in 9 categories of breeding habitats in Panaji, Goa, showed that 1.1% of the 67,360 breeding sites contained Anopheles stephensi immatures and the overall positivity varied from 0.4 to 3.5% with a peak in June. The habitat-wise proportion of An. stephensi was: wells, 0-1.3%; fountains, 1.4-11.4%; masonry tanks, 0.8-6.1%; overhead tanks, 0.1-4.0%; curing water in construction sites, 0.6-9.0%; groundwater tanks, 0-1.4%; tyres, 0-8.9%; barrels and tins, 0-5.4%; and intradomestic containers, 0-1.9%. An. stephensi was breeding along with An. subpictus, An. vagus, An. barbirostris, Culex quinquefasciatus, Cx. vishnui, Ae. aegypti, Ae. albopictus and Ae. vittatus. PMID- 1459299 TI - Reversal of chloroquine resistance with verapamil in P. berghei in vivo. AB - The effects of verapamil on the parasite susceptibility to chloroquine were examined in mice infected with chloroquine-sensitive and chloroquine-resistant lines of Plasmodium berghei. Verapamil in a dose of 10-50 mg/kg daily s.c. for 4 days did not affect the growth of both sensitive and resistant parasites. When verapamil in the same dose range was combined with 1.5 mg/kg chloroquine diphosphate, the chloroquine-sensitive parasites became more susceptible to chloroquine. Similarly, verapamil severely suppressed the growth of chloroquine resistant parasites in combination with 3 mg/kg (base) of chloroquine, but the reversal of resistance was not complete. Thus, still higher doses of verapamil, which are not tolerated by the host, are required for the complete reversal of resistance. PMID- 1459300 TI - Anopheline breeding in ponds of central Gujarat with reference to water hyacinth infestation. PMID- 1459301 TI - Malaria morbidity survey in schoolchildren in age group 5-15 years in an urban area. PMID- 1459302 TI - Enhancing the efficacy of Gambusia affinis to control mosquito breeding in ponds. PMID- 1459303 TI - Biochemical alterations in Plasmodium vivax-infected malarial patients before and after radical treatment. AB - Biochemical alterations in 152 malaria patients infected with Plasmodium vivax were studied and the effect of parasitaemia on these changes was assessed. The degree of parasitaemia correlated positively with plasma uric acid, total and unconjugated bilirubin. A decrease in the levels of serum total protein, albumin, serum total, free and ester cholesterol was observed in vivax malaria. A follow up study done on a section of the above patients after administration of chloroquine and primaquine for radical treatment of malaria showed the most of the alterations observed were bought back to normal. However, blood haemoglobin level was not restored to normal even after ten days of commencement of treatment. PMID- 1459304 TI - Gambusia affinis: dispersal due to floods and its failure to colonize new water bodies in Shahjahanpur District (U.P.). AB - In villages of District Shahjahanpur, 122 decentralized Gambusia multiplication ponds were established to cover the need of the entire district. Profuse breeding of Gambusia was observed in these ponds. The fishes are being successfully used in mosquito control all over the district. In July 1990 there was a widespread flood due to which 70 Gambusia multiplication ponds were affected and the fish was washed away in large numbers, leaving only a scanty population in the flood affected ponds. We utilized this opportunity to study the natural dispersal and colonization of Gambusia in different aquatic habitats. The study revealed that Gambusia was either not found in most habitats or was present in very small numbers, and on its own Gambusia was unable to eliminate the local fauna to become a dominant species. Predatory fishes and birds played a major role in eliminating Gambusia. Gambusia is therefore unlikely to pose any ecological hazard in vector-control programmes. PMID- 1459305 TI - Socio-cultural factors associated with malaria transmission: a review. PMID- 1459306 TI - Involvement of gastrointestinal tract in Plasmodium vivax Malaria. PMID- 1459307 TI - Some observations on Plasmodium falciparum gametocytaemia in natural infections in an endemic area of Koraput district, Orissa. AB - Peripheral P. falciparum gametocytaemia with respect to its minimum average time taken for appearance in peripheral blood, its peak density, duration of persistence in peripheral circulation, conversion rate and sex ratio was studied in 22 persons with natural infections in a village of Koraput district, Orissa. The minimum average time taken for the appearance of gametocytes was 9.3 days in children (below 15 years) and 8.9 days in adults (15 years and above). The peak count was low, the maximum density being 31/microliters. The duration of gametocytaemia in peripheral circulation was also short, the longest being 32 days. The gametocyte conversion rate on an average was 0.74% in children and 2.04% in adults. The mean sex ratio of micro:macro gametocytes was 1:2.6 in children and 1:6.2 in adults. PMID- 1459308 TI - Effect of tissue culture media on multiplication of Plasmodium falciparum in vitro. AB - To date RPMI-1640 has been the best medium for cultivation of Plasmodium falciparum in vitro. In addition to this medium, several alternative media, essentially the ones used in animal and plant tissue culture, were employed for the cultivation of P. falciparum. Only the media rich in glucose content, viz. Nitsch medium and White's medium S-3, supported the parasite multiplication. PMID- 1459309 TI - Microscopic diagnosis of malaria in Kheda district of Gujarat. AB - A study conducted in 1990 revealed that 2% (range 0.6-4.8) of negative blood smears were mislabelled as positive, and 6.7% of positive blood smears were mislabelled as negative. A result of such mislabelling would be inadequate treatment of a large number of patients. Hence the need to look into the training aspect and system of supervision of laboratory technicians. The present system of cross-checking of blood smears at different levels also needs to be reviewed. A study which could address itself to these needs is indicated. PMID- 1459310 TI - Problem of antimalarial drug resistance in Plasmodium falciparum in Mizoram. AB - Studies conducted in Mizoram during 1981 to 1990 have shown areas with increasing RIII level of chloroquine resistance. These foci need urgent liquidation. Sulfalene-pyrimethamine drug combination was found suitable for treatment of P. falciparum cases in these areas with only 5.3 per cent cases showing RI level of Plasmodium response. Quinine combined with sulfalene-pyrimethamine showed 100 per cent success. Amodiaquine however was similar in response to chloroquine though the mean parasite clearance time with amodiaquine was slightly better. PMID- 1459311 TI - Management of admitted malaria cases in four major hospitals of Delhi: a case study. AB - A hospital-based retrospective case study of admitted patients was undertaken in four major hospitals of Delhi during 1991, with a view to assessing (i) recording and reporting system of malaria cases, (ii) diagnostic criteria being followed, (iii) management of complicated and severe malaria cases, and (iv) availability of life-saving antimalarials. The study showed that none of the hospitals either followed the international coding system for recording or adopted the National Malaria Eradication Programme guidelines for diagnostic criteria malaria, i.e. by blood smear examination. Diagnosis of malaria in three out of four hospitals was not preceded by blood examination in all cases. Only 55% of the 283 clinically suspected malaria cases were screened for malaria parasite with overall positivity of 20.14 per cent and of 38.25 per cent in examined cases. Age and sex break-up indicated that males suffered more and 65 per cent of the patients belonged to 16-40 years' age groups as compared to 38.4 per cent population falling in this age group according to 1981 census. Out of 263 recovered study cases, 13 per cent came from adjoining states while this percentage went up to 35 per cent (7 out of 20 cases) in the case of malaria deaths. Over 80 per cent of the clinically suspected cases presented with signs and symptoms of fever or fever with rigour, chills or vomiting. In 38 per cent of the cases there was a definite time lag in reporting of the cases to hospitals but most of the cases (91 per cent) were administered antimalarials within 24 h of admission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459312 TI - [The role of the HLA system in the genetics of Type I diabetes mellitus]. AB - Major determinants of susceptibility to Type 1 (insulin-dependent) diabetes (IDDM) have been mapped to the HLA complex, near to or identical with genes encoding class II molecules. The association of IDDM with HLA-DR3 and/or DR4 antigens and the highest risk for DR3/4 heterozygotes suggest a synergistic effect of the two haplotypes. The characterization at the molecular level of the class II region has provided evidence that DQ rather than DR determinants may primarily influence the disease. In caucasians the susceptibility strongly correlates with the absence of aspartic acid at position 57 on the DQ beta chain and/or the presence of arginine at position 52 on the DQ alpha chain. The formation of a putative DQ susceptibility molecule (DQ alpha Arg52+, DQ beta Asp57-) accounts best for the disease associations when trans-complementation between alpha and beta chains encoded by different haplotypes is postulated to explain the excess of heterozygotes. Observations in other populations and in animal models indicate, however, that other residues on DQ alpha and beta chains, other class II (DR beta) molecules and non-HLA linked genes also contribute to the susceptibility. The mechanism(s) by which susceptibility determinants influence IDDM is not known. It is probably in relation with the role of class II molecules in the antigen presentation to T lymphocytes. PMID- 1459313 TI - Increased lipid peroxidation in type 2 poorly controlled diabetic patients. AB - An increased lipid peroxidation, due to the altered intracellular ratio between free radicals and antioxidant systems, has been recently related to diabetes. To study the possible relationship between lipid peroxidation and metabolic control, we measured the plasma concentrations of malondialdehyde (MDA), end product of the oxidation of polyunsaturated fatty acids, in poorly and well controlled Type 2 diabetic patients. A significant increase in plasma malondialdehyde concentrations was found in poorly controlled diabetics when compared to well controlled patients (p < 0.001) and to healthy normoglycaemic subjects (p < 0.001), whereas no significant difference was observed between the two latter groups. Plasma MDA/Cholesterol and MDA/triglyceride ratios were both higher in poorly controlled diabetics than in well controlled (p < 0.005) and in normal subjects (p < 0.01 and p < 0.02 for MDA/CHOL and MDA/TG respectively). In diabetic patients a positive correlation was found between plasma MDA levels and mean daily blood glucose (p < 0.01), plasma fructosamines (p < 0.001), HbA1 (p < 0.05) and plasma triglycerides (p < 0.05), while no significant correlation was shown between plasma malondialdehyde and total cholesterol. Malondialdehyde levels were followed-up for 7 days running (T1-T7) in five poorly controlled diabetics, treated with conventional insulin therapy. This group showed normalized plasma lipid peroxide values (0.486 +/- 0.13 mumol/l, T5, M +/- SEM) 72 h after the restoration of glycaemic control (145 +/- 25 mg/dl, T2, M +/- SEM). These results confirm the increase of lipid peroxidation during Type 2 diabetes. The correlation with the degree of metabolic imbalance suggests a possible role for lipid peroxidation in the occurrence of glucose-induced macromolecular changes. PMID- 1459314 TI - Intermediate and long-acting insulin preparations without protamine sulphate are complement activators in vitro. AB - Recently, we have documented an abnormal in vivo complement metabolism in Type 1 diabetic children treated with monocomponent porcine insulin Monotard MC and its correction after switch-over to human insulin Protaphane HM. This prompted us to investigate the ability of different kinds of insulin preparations to induce complement activation in vitro. Freshly collected serum samples from healthy blood donors were incubated with commercial rapid and intermediate or long-acting (by protamine sulphate (PS) or zinc) insulin preparations for 2 hours at 37 degrees C. The C3d content of the supernatants was measured by turbidimetry as a marker of C3 complement fraction consumption. Only long-acting preparations of insulins without protamine sulphate were associated with highly significant increased levels of C3d, whatever the source of insulin, animal or human. Moreover, addition of exogenous protamine sulphate was able to inhibit the C3 conversion. This effect was dose-dependent and peaked at the concentration of commercial NPH insulin preparations. The mechanism by which protamine sulphate inhibits complement activation in vitro could be related to its ability to interfere with the physical nature of the solid surfaces presented by the insulin crystals. Indeed, insulin crystals were rapidly cleared (< 5 min) in the incubated serum when small doses of protamine sulphate were added. The complement activating capacity of long-acting insulin without protamine was dose dependent, equivalent to the known complement activator Zymosan, and abolished in the presence of EDTA. In conclusion, the present study has documented the ability of some protracted insulin preparations to activate the complement system in vitro if they are devoided of protamine sulphate. On the other hand, short-acting and NPH insulins are not complement activators. PMID- 1459315 TI - Differential effects of insulin-induced hypoglycaemia on the plasma branched chain and non-branched-chain amino acid concentrations in humans. AB - In order to determine plasma amino acid concentrations during a prolonged but moderate insulin-induced hypoglycaemia, six healthy volunteers received a constant subcutaneous insulin infusion (15 mU.m-2.min-1) over a 12 hour period. The plasma glucose concentrations decreased from 4.72 +/- 0.11 to 2.83 +/- 0.07 mM at 600 minutes and then remained stable over the last 120 minutes. Plasma counterregulatory hormones (glucagon, epinephrine, growth hormone and cortisol) increased significantly between 120 and 180 minutes. The plasma concentration of all the amino acids paralleled the decrease in plasma glucose. The branched chain amino acids decreased to a greater extent in the first part of the study (0-360 min) in comparison to the essential non-branched chain aminoacids (p < 0.01), then increased significantly with a peak at 600 minutes (p < 0.05 vs 360 min) despite stable hyperinsulinaemia. These results suggests that during prolonged but moderate hypoglycaemia the counterregulatory hormones are able to antagonize partially the effects of insulin on protein metabolism, analogous to their well known anti-insulin effects on glucose and fatty acid metabolism. PMID- 1459316 TI - Short-term metabolic effects of the ACE-inhibitor benazepril in type 2 diabetes mellitus associated with arterial hypertension. AB - To assess the short-term metabolic effects a long-acting non-sulphydryl ACE inhibitor benazepril on glycaemic control in Type 2 diabetes mellitus and arterial hypertension, 10 hypertensive diabetic patients treated with glibenclamide were studied in a double-blind, crossover fashion over two 10-day periods in which either benazepril (10 mg/day) or placebo was given. At the end of the 10 day treatment, both blood pressure and plasma glucose concentrations were lower after benazepril versus placebo (benazepril, blood pressure: 143 +/- 11/83 +/- 5 mmHg, plasma glucose: 7.1 +/- 1.2 mmol/l; placebo: blood pressure: 157 +/- 10/99 +/- 2 mmHg, plasma glucose: 8.2 +/- 1 mmol/l, p < 0.05). In response to an oral glucose tolerance test combined with 1 mg intravenous glibenclamide, plasma glucose levels were lower after benazepril versus placebo (0-460 min: 8.4 +/- 0.8 versus 10.5 +/- 0.9 mmol/l, p < 0.05), whereas plasma insulin, C-peptide and glibenclamide concentrations were not different. It is concluded that a short-term administration of benazepril in Type 2 diabetes mellitus reduces blood pressure and improves blood glucose control, most likely by decreasing insulin resistance. PMID- 1459317 TI - Influence of obesity and hypertriglyceridaemia on the low HDL2-cholesterol level and on its relationship with prevalence of atherosclerosis in type 2 diabetes. AB - High density lipoprotein subfraction 2 (HDL1)-cholesterol level is usually decreased in Type 2 (non-insulin-dependent) diabetes. A study was carried out in 251 Type 2 diabetic patients (106 males [M], 145 females [F]) and in 120 non diabetic controls in order to determine the influence of hypertriglyceridaemia and obesity on the HDL2-cholesterol level and to analyse the relationship between HDL2-cholesterol level and atherosclerosis (coronary heart disease, peripheral atherosclerosis or cerebral vascular disease), in Type 2 diabetes. Influence of hypertriglyceridaemia and obesity on HDL2-cholesterol level was studied by comparing the mean values of HDL2-cholesterol between diabetics and controls, after controlling for hypertriglyceridaemia and obesity, and by a multiple linear regression test. A stepwise logistic regression was performed to analyse the association between the prevalence of atherosclerosis and several variables: age, duration of diabetes, hypertension, cigarette smoking, body mass index, mean glycaemia, total cholesterol, triglyceride, HDL-cholesterol, HDL2-cholesterol and HDL3-cholesterol levels. In both men and women, when both of the factors (hypertriglyceridaemia and obesity) were present of when only one was, HDL2 cholesterol level was significantly lower in the diabetic population, compared with controls. But when obesity and hypertriglyceridaemia were absent, HDL2 cholesterol level, in the diabetic population, was not significantly different from controls (M: 17.9 +/- 13.3 vs 20.5 +/- 13.8 mg/dl: NS; F: 30.1 +/- 21.5 vs 27.6 +/- 14.2 mg/dl: NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459318 TI - [Respective weight of genotypes DQA1 and DQB1 associated with insulin-dependent diabetes in French children]. AB - Genetic susceptibility alleles have been identified at the DQ HLA region. The aim of the present study was to confirm the value of these markers, and to evaluate the respective weight in the risk of the different alleles at the DQA1 and DQB1 levels, identified by restriction mapping after polymerase chain reaction on exon 2. A significant enrichment in DQB1 alleles encoding for an aminoacid different from Aspartic acid at position 57 (NA) was observed in diabetic (n = 213) in comparison to control (n = 93) children (94% vs 52%; p < 10(-8)). Not all the given NA/NA allelic combinations were equally and positively associated to the disease. Homozygous "Ala/Ala" combinations carried the highest relative risk (OR = 12.3; p < 10(-8)), and among them, the *0201/*0302 genotype was more positively associated to type 1 diabetes (OR = 66; p < 10(-8)). A significant enrichment in DQA1 alleles encoding for Arginine at position 52 in diabetic children was also observed (82% vs 40%; p < 10(-8)). The *0301/*0501 (Arg/Arg) genotype was significantly associated to Type 1 diabetes (OR = 16.2; p < 10(-4)). The highest risk was carried by the whole genotype, a result which could be expected from the known linkage desequilibrium between HLA-DQA1 and DQB1, DRB1 loci. The frequency of Ala DQB1 alleles was low in the background non-at-risk population, although the incidence of the disease is low in our country. PMID- 1459319 TI - Similarity of HLA-DQ profiles in adult-onset type 1 insulin-dependent diabetic patients with and without extra-pancreatic auto-immune disease. AB - Some insulin-dependent diabetic patients present with auto-immune diseases involving extra pancreatic tissues (type 1b diabetes mellitus). The genetic specificity of this syndrome, as opposed to insulin dependent diabetes mellitus (IDDM) free of such associations (Type 1a IDDM) is not clearly established. We have analyzed the HLA-DQB1 and DQA1, loci, after PCR amplification of genomic DNA, in 44 Type 1b IDDM patients, 78 Type 1a IDDM patients and 105 control subjects. No essential difference in HLA-DQ profiles appeared between Type 1b and Type 1a IDDM patients. Both diabetic groups displayed a significant enrichment in DQB1 alleles negative for aspartate at position 57 (Type 1b: 83%; Type 1a: 89%; controls 48%; p < 0.001 vs both patient groups) and in DQB1 Asp 57 negative homozygosity: 71% of Type 1b; 80% of Type 1a; 25% of controls (p < 0.01). This enrichment in DQB1 Asp 57 negative alleles was accounted for by DQB1* 0201 in the Type 1b group, and by DQB1 % 0201 and 0302 in the Type 1a patients. Conversely, alleles DQB1* 0602 and 0301 (DQB1 Asp 57 positive) were protective. Both diabetic groups also displayed a significant enrichment in DQA1 alleles positives for arginine at position 52 (65% of Type 1b; 76% of Type 1a; 50% of control subjects; p < 0.01 and 0.001, respectively, vs controls), and in DQA1 Arg 52 positive homozygotes (48% of Type 1b, 58% of Type 1a, 22% of control subjects; p < 0.01). All differences between diabetic groups and the control group were more pronounced in the case of Type 1a than of Type 1b patients. The HLA-DQ genes shared by Type 1a and Type 1b patients must therefore be closely associated with islet autoimmunity. Genetic differences between Type 1a and Type 1b syndromes, if any, must be investigated in other MHC and non-MHC regions of the genome. PMID- 1459320 TI - [Transition from insulin U40 to U100]. PMID- 1459321 TI - [Transition from insulin U-40 to insulin U-100: the Belgian experience]. PMID- 1459322 TI - [Reverse genetics of positional cloning]. PMID- 1459323 TI - Hair zinc and dietary zinc intake during pregnancy and puerperium. AB - A longitudinal study of hair zinc concentration was carried out in 36 pregnant women at 12 and 36 weeks of gestation and 40 days postpartum. A progressive decrease in hair zinc concentration was noted through pregnancy; the decline between 12 and 36 weeks of gestation was statistically significant (P < 0.005) remaining without significant changes in the postpartum. Nutrient intakes were calculated from 3-day weighed food records at the same periods and at 20 weeks of gestation. Zinc, energy and protein intakes decreased during pregnancy. Mean zinc intake at 20 and 36 weeks of gestation was about 66% of the recommended dietary allowance (RDA) (9.8 and 10 mg, respectively) and about 52% of the RDA in the postpartum (9.8 mg). Although hair zinc levels do decline in pregnancy and zinc intake was lower than RDA, the study revealed that zinc nutriture was adequate for normal growth and development of fetus. PMID- 1459324 TI - Cytogenetic analysis of spontaneous abortions with direct analysis of chorionic villi. AB - A total of 224 cases of spontaneous abortions were studied by analysing chromosomes directly from chorionic villi. Abnormal karyotypes were found in 51.3% of the investigated cases. Among the chromosome abnormalities the most frequent were the trisomies (55.7%), followed by polyploidy (23.5%), monosomy X (15.6%) and structural anomalies (5.2%). The rapid and relatively simple method is suitable for studying the causes of spontaneous abortions, and this information may be helpful also for genetic counselling. PMID- 1459325 TI - The reliability, acceptability and applications of basal body temperature (BBT) records in the diagnosis and treatment of infertility. AB - The possibilities and limitations of basal body temperature (BBT) records as an adjunct in the management of infertility were re-evaluated. To assess its accuracy as an index of ovulation, 172 charts were analyzed by three different physicians. While the average true positive rate was 90%, the false negative rate was only 2%. The remaining graphs (8%) were classified as non-interpretable, probably reflecting measurement problems. Retrospective assessment of 210 biphasic records showed the thermal nadir to occur within 1 day of the urinary luteinizing hormone (LH) surge in 75% of the cases, and in 90% when 2 days where considered. This confirms BBT as a relatively accurate guide for retrospective identification of the periovulatory period. Moreover, results of a study conducted to investigate how patients experienced daily recording of BBT graphs suggest that the method is well accepted by a high proportion of women. From all these it appears that there are many indications where BBT graphs can still be applied. Development of new electronic devices may further improve the reliability, acceptability and applications of the BBT records in the fertility investigation. PMID- 1459326 TI - Paradoxical ovarian stimulations in the use of LHRH analogs. AB - In the case of in vitro fertilization, LHRH analogs are used to induce an hypophysary blockage, before the phase of stimulation, via administration of exogenous gonadotropin. During in vitro fertilization attempts using LHRH analogs, the blockage is controlled after 14 days of treatment through measurement of the plasmatic estradiol and pelvic ultra-sonography. In this retrospective study, which concerned 1075 in vitro fertilization cycles, a paradoxical ovarian stimulation with LHRH analogs was observed in 93 cases (8.7%), with high estradiol levels and follicular growth (detected by ultra sonography), in spite of low FSH and LH levels. In 4 cases, a follicular puncture was performed, which allowed to collect oocytes from which embryos were obtained, thus confirming the observed follicular growth and maturation. The most probable hypothesis explaining this phenomenon seems to be a direct ovarian stimulation, effectuated in vivo by LHRH analogs. This stimulation is only observed in certain patients, and apparently more frequently, with certain LHRH analogs, probably through a variation in the expression of ovarian LHRH receptors. PMID- 1459327 TI - The unicornuate uterus: clinical implications. AB - The unicornuate uterus is associated with a poor reproductive outcome and many gynecological problems. We collected data from 45 women with a unicornuate uterus. We found a high abortion rate of 22% in the first trimester and 16% in the second trimester. Premature labor occurred in 18%. The prevalence of infertility and endometriosis in women with a unicornuate uterus was comparable to women without the anomaly. PMID- 1459328 TI - Early stage cervical cancer: aborted versus completed radical hysterectomy. AB - In a retrospective study, the treatment results of patients with stage IB and IIA cervical cancer were evaluated. In 26 patients radical hysterectomy was discontinued after intra-operative finding of positive lymph nodes. These patients received radiotherapy. In 57 patients lymph nodes were negative, and radical hysterectomy was completed. Of these, 13 patients received adjuvant radiotherapy because of positive surgical margins or parametrial involvement, and 44 patients received no adjuvant therapy. Five-year survival was 61% in patients with positive pelvic lymph nodes and 88% in patients with negative pelvic lymph nodes, comparable with the results mentioned in the literature. The complication rate did not differ from similar other reports. This management shows treatment results comparable with other reports with minimal morbidity. PMID- 1459329 TI - Beneficial effects on serum lipoproteins by 17 beta-oestradiol-dydrogesterone therapy in postmenopausal women; a prospective study. AB - STUDY OBJECTIVE: To study the possible changes of reproductive hormones, sex hormone binding globulin, serum lipids and lipoproteins, lipoprotein (a) included, coagulation and glucose in postmenopausal women treated with 17 beta oestradiol and cyclic dydrogesterone for 14 days per 28 days treatment cycle. DESIGN: Open longitudinal prospective study. DURATION: Twelve 28 days treatment cycles. SETTING: Gynaecological department of university hospital. SUBJECTS: 27 healthy postmenopausal women. RESULTS: After treatment for six cycles serum concentrations of FSH and LH decreased significantly with 43.0% and 24.4%, respectively. Serum concentrations of 17 beta-oestradiol and oestrone increased significantly with 302% and 792%, respectively, and SHBG increased as well with 111% (P < 0.01). Serum total cholesterol decreased with 9.0% (P < 0.01). Serum VLDL-cholesterol did not change significantly. Serum LDL-cholesterol decreased with 16.3% (P < 0.01) and HDL-cholesterol increased with 8.0% (P < 0.01). This was accompanied with similar significant changes in the apolipoproteins: apolipoprotein A-I rose with 14.4% and apolipoprotein B decreased with 6.0%. Serum triglycerides and VLDL-triglycerides increased significantly with 14.4% and 17.9%, respectively. Lipoprotein (a) decreased with 17.5% (P < 0.01). These results more or less sustained at cycle 12 of treatment. Serum concentrations of antithrombin III and glucose did not change. Fibrinogen decreased slightly but significantly below the initial value. CONCLUSIONS: This combination replacement therapy gives beneficial changes in lipid-metabolism, indicating a reduced risk of developing coronary heart disease without unfavourably changing coagulation and glucose metabolism. The expected beneficial changes with oestradiol alone are not counteracted by the intermittent addition of dydrogesterone. Therefore this oestrogen/progestagen scheme can, indeed, be recommended for use in HRT. PMID- 1459330 TI - Ultrasound diagnosis of interstitial pregnancy. AB - A case of interstitial pregnancy is reported. The diagnosis was made by ultrasound examination in an asymptomatic patient at risk for ectopic pregnancy following cornual anastomosis. Characteristic sonographic signs are discussed, with a review of the literature. PMID- 1459331 TI - Vulvar pseudolymphoma. AB - We report a 31-year-old patient with longstanding complaints of vulvar itching and painful intercourse treated with many antimycotic drugs. On examination a small tumor, clinically not differentiable from a malignant lymphoma, on and near the clitoris was found. After excision biopsy the lesion proved to be a pseudolymphoma. Six months after excision of this rare vulvar tumor the patient was completely free of complaints. Although pseudolymphomas are small benign tumors they may case diagnostic problems and major complaints. To our knowledge this very rare disorder has not been reported in the gynecological literature until now. PMID- 1459332 TI - Post-menopausal cyclic eruptions: autoimmune progesterone dermatitis. AB - Two cases of autoimmune progesterone dermatitis (AIPD) are reported. The patients developed a recurrent eruption, primarily on the extremities after receiving oral oestrogen/progesterone replacement for the treatment of climacteric symptoms. The diagnosis was confirmed in one of the cases who had intradermal progesterone injection producing an early positive reaction. One case required transient prednisolone therapy and both eventually resolved completely. Aetiological postulates are discussed. PMID- 1459333 TI - Doppler velocimetry of the umbilical artery in pregnancies complicated by insulin dependent diabetes mellitus. AB - The purpose of this study was to investigate vascular resistance by Doppler ultrasound in the umbilical artery of insulin-dependent diabetics longitudinally over the course of pregnancy. Special interest was put on the effects of glycemic control and maternal vascular disease on the flow velocity waveform (FVW) and the predictive value of Doppler flow measurements with regard to perinatal morbidity. Using a duplex-pulsed wave scanner, the resistance-index (PR index) in the umbilical artery was calculated. The mean value of a 24-h blood glucose profile and the concentration of glycosylated hemoglobin (HBA1C) were used as parameters of metabolic control. 53 pregnant diabetic women were examined longitudinally during the course of pregnancy on average on three occasions (range: 1-7) between 17 weeks of gestation and delivery at 37.7 +/- 1.3 (mean +/- SD) weeks. To test the predictive value of Doppler flow velocimetry with regard to perinatal morbidity the results were compared to the FVWs measured in the umbilical arteries of 30 non-diabetic women with normal fetal outcome. Vascular resistance in the umbilical artery of the diabetics declined significantly during the course of pregnancy, with a mean PR index of 0.729 (SD 0.051) at 17 weeks and 0.603 (SD 0.083) at the end of pregnancy (P < 0.002). The majority of PR indices were within the range reported for normal pregnancy and measured in the non-diabetic women. Regression analysis showed no significant correlation between vascular resistance and mean blood glucose level (r = 0.1325) or concentration of HBA1C (r = -0.0519). Maternal vascular disease had no effect on umbilical FVWs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459334 TI - Inhibition of binding of bacteria to amniochorionic membranes by amniotic fluid. AB - The immunological composition of amniotic fluids is shown to be of such a lower order of activity that its role in fetal protection may be limited. Also, amniotic fluids were found not to have classical antibiotic activity. Amniotic fluids (25/31), however, were found to inhibit, by 27.5% to 88.2%, three target bacteria from binding to discs of amniochorionic membranes. This inhibition is also demonstrable with the monosaccharides alpha-D(+)-fucose, D(+)-galactose, alpha-D-glucose, alpha-D-lactose and bovine serum albumin-lactose conjugate, whereas other glycoconjugates enhanced bacterial binding. This demonstrates that the test bacteria bind to the amniochorionic membranes using bacterial lectins. In intraamniotic infection bacterial lectins may be complexed by amniotic fluid glycoconjugates which prevent the bacteria from binding to the amniochorionic membranes. This would explain asymptomatic infection and in the absence or reduced levels of the glycoconjugates the bacteria would bind to the amniochorionic membranes giving rise to symptomatic infection. PMID- 1459335 TI - Calbindin-D9k gene expression during pregnancy and lactation in the rat. AB - Calbindin-D9k (CaBP-9k) is a calcium binding protein expressed in mammalian intestine, uterus and placenta. It is believed to be involved in transepithelial calcium transport in intestine and placenta and regulation of cytosolic calcium concentration in uterus. CaBP-9k mRNA levels were measured by Northern blot analysis in maternal duodenum, uterus, placenta and fetal/neonatal duodenum during pregnancy and lactation. In maternal duodenum a maximal increase occurred at day 15 of lactation (2.3-fold) and 20 days post-lactation levels decrease to 30.3% of non-pregnant controls. In non-pregnant uterus a 10-fold variation of CaBP-9k mRNA levels was observed between individual animals despite a uniform expression of beta-actin. During pregnancy high CaBP-9k expression is found, averaging about 20% of duodenal levels, which abruptly drops below detection during early lactation. At late lactation CaBP-9k mRNA levels are again subject to great variation ranging from no expression to maximal levels found in the non pregnant uterus. Placental CaBP-9k is maximally expressed at the end of pregnancy (day 20) reaching about 2.5% of duodenal levels. Fetal intestinal CaBP-9k mRNA was detectable in 20 micrograms total RNA at day 18 of pregnancy and rose sharply in early lactation reaching about 50% of adult duodenal levels at day 20 lactation. The profound changes of uterine CaBP-9k mRNA in non-pregnant (cycling), pregnant, and lactating rats indicate a rapid hormonal regulation of gene expression, most likely involving 17 beta-estradiol. PMID- 1459336 TI - Rat oocytes induced to mature by epidermal growth factor are successfully fertilized. AB - Epidermal growth factor (EGF), which is a known mitogen, can also induce resumption of meiosis in the rat oocyte. The present study was designed in an attempt to elucidate whether oocytes, induced to mature by EGF in a follicle enclosed oocyte culture, are fertilizable and can further develop into two-cell embryos. For further clarification of the effect of EGF on steroidogenesis in the ovarian follicle, progesterone concentrations were determined by radioimmunoassay. We found that oocytes matured by EGF (100 ng/ml) were successfully fertilized. Even though their rate of fertilization was relatively lower as compared to that of oocytes stimulated by luteinizing hormone (LH) both in vitro and in vivo (61%, 79%, and 83% respectively), once fertilized they exhibit an equal potential for further development (EGF: 48%, LH: 45%). On the other hand, EGF-induced progesterone production was very poor. These findings strongly support the idea that both mitogenesis and meiogenesis can be mediated by common signals. The results further suggest that progesterone production and oocyte maturation, in the rat, are independent events. PMID- 1459337 TI - Interaction of the 90-kDa heat shock protein with native and in vitro translated androgen receptor and receptor fragments. AB - Androgen receptor (AR) from rat ventral prostate and AR synthesized in vitro by translation in rabbit reticulocyte lysate of AR mRNA, transcribed from a pGEM-4Z DNA template were compared by gel permeation chromatography and by sucrose gradient ultracentrifugation. Under non-activating conditions the AR from rat prostate migrated as an 8-9 S complex of approx. 300 kDa. The addition of chicken antibodies against HSP90 shifted this complex to the void volume of the column or to the bottom of the ultracentrifugation gradient. Under activating conditions, on the other hand, the AR migrated as a 110 kDa, 5.2 S protein and was no longer displaced by HSP90 antibodies. Under all these conditions, the behaviour of in vitro synthesized AR was very similar to that of AR from rat prostate. By selective use of restriction enzymes on the template of transcription AR mutants could be prepared from which an increasing part was deleted at their carboxy terminal end. The interaction with HSP90 was conserved for AR1-758 missing the last 145 amino acids, but was lost in AR1-703. Furthermore, a large internal deletion (ARd41-469) of the major part of the amino terminal half of the AR did not result in the loss of HSP90 binding. These results indicate that a specific subregion (amino acids 704-758) of the carboxy terminal half of the AR is required for the interaction with HSP90. PMID- 1459338 TI - Identification of a transcriptional enhancer upstream from the bovine thyroglobulin gene. AB - The DNA sequences corresponding to a DNaseI-hypersensitive region identified previously in bovine thyroglobulin gene chromatin (Hansen et al. (1988) Eur. J. Biochem. 178, 387-393) exhibited the properties of a transcriptional enhancer in a transient assay in primary cultured dog thyrocytes, but did not so in transfected HeLa cells. By contrast to the thyroglobulin proximal promoter, the enhancer element did not require cyclic AMP stimulation of the thyrocytes to be active. Using a bi-directional deletion approach, the minimal region displaying enhancer activity has been localized between positions -1906 and -1744 relative to the thyroglobulin gene transcription start. DNA-footprinting experiments revealed the presence of several binding sites for the thyroid-specific transcription factor TTF-1 within the enhancer sequence. PMID- 1459339 TI - Evidence for basic fibroblast growth factor receptors in cultured immature Leydig cells. AB - Previous studies have shown that basic fibroblast growth factor (bFGF) can modulate basal and luteinizing hormone/human chorionic gonadotropin (LH/hCG) stimulated Leydig cell functions. It has not been ascertained whether these actions are due to direct or indirect effects on Leydig cells. To resolve this question, a multi-step procedure was used to isolate highly-purified Leydig cells from immature rats. 125I-bFGF binding studies were performed on cultured cells. Scatchard analysis of the data indicated a single binding site with an apparent Kd of 82 pM and a binding capacity of approximately 2800 sites per cell. Both bFGF and acidic FGF similarly were effective in displacing 125I-bFGF, suggesting that the receptor binds both bFGF and aFGF. However, neither hCG, follicle stimulating hormone (FSH), insulin, insulin-like growth factor-1 (IGF-1), prolactin, platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) were effective competitors. When binding studies were conducted on cultured testicular interstitial cellular fractions that are normally discarded during Leydig cell purification, bFGF receptors were identified in these fractions. These results demonstrate that bFGF can have direct effects on Leydig cells through specific receptors; however, because other interstitial cell type(s) also have bFGF receptors, they stress the importance of using highly purified cells when evaluating bFGF actions on Leydig cells. PMID- 1459340 TI - Biphasic effects of exogenous ganglioside GM3 on follicle-stimulating hormone dependent expression of luteinizing hormone receptor in cultured granulosa cells. AB - The major ganglioside NeuAc alpha 2-->3Gal beta 1-->4Glc beta 1-->1Cer (GM3) present in cultured rat granulosa cells was examined for potential function in the expression of luteinizing hormone (LH) receptor on the cell surface in response to follicle-stimulating hormone (FSH). Synthesis of GM3 was stimulated concentration-dependently by FSH, and the stimulation was enhanced synergistically by insulin, as revealed by metabolic labeling of glycosphingolipids with [3H]galactose. When granulosa cells were cultured in the media containing GM3 (0.2-20 microM), biphasic changes in FSH-dependent expression of LH receptor were observed, as measured by the binding of 125I deglycosylated human choriogonadotropin to the intact cells. Exogenous GM3 suppressed expression of LH receptor in the cells treated with a low dose of FSH (20 ng/ml), which was characterized by a low GM3 level, to 30% of control at 10 microM, with a half-maximal inhibitory concentration of 8 microM. In contrast, in the cells treated with a high dose of FSH (100 ng/ml) and insulin, which was characterized by a high GM3 level, expression of LH receptor was enhanced by exogenous GM3, to 148% of control at 10 microM, with a half-maximal effective concentration of 2 microM. Exogenous GM3 produced concomitant changes in the levels of extracellular cAMP. These effects of exogenous GM3 were not accompanied by changes in granulosa cell proliferation. Exogenous GM3 also modulated the LH receptor expression by the synergistic action of 12-O-tetradecanoylphorbol 13 acetate with insulin, with no significant changes in cellular DNA contents, suggesting that exogenous GM3 does not modulate directly the action of FSH at its receptor sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459341 TI - The murine luteinizing hormone and follicle-stimulating hormone receptor genes: transcription initiation sites, putative promoter sequences and promoter activity. AB - The putative promoter regions of the murine follicle-stimulating hormone (FSH) and luteinizing hormone (LH) receptor genes were isolated and used to map transcription initiation sites for both genes. For the FSH receptor gene, a major transcription initiation site was found 534 nucleotides upstream, and for the LH receptor gene 310 nucleotides upstream of the corresponding translation initiation codons. In addition, several alternative minor transcription initiation sites were observed for both genes. The nucleotide sequences of the promoter regions revealed no canonical promoter elements, such as TATA and CCAAT consensus sites 5' of the main transcriptional start sites. The isolated promoter segments for both receptor genes showed low functional activity as verified in transient expression studies in immature rat granulosa cells using the luciferase coding region as the reporter for promoter activity. Both promoter elements seem to be still under tissue specific control, since neither LH receptor nor FSH receptor promoter activity was detectable in another cell line (CHO) investigated. PMID- 1459342 TI - Differential regulation of anterior pituitary prodynorphin and gonadotropin subunit gene expression by steroid hormones. AB - Prodynorphin is expressed by neurons of the hypothalamus and gonadotrophs of the anterior pituitary gland (AP) and plays a role in the negative feedback regulation of the reproductive neuroendocrine axis. The present study examined whether gonadal steroid hormones are capable of modulating pituitary prodynorphin expression in immature, female rats. Steroids were administered via subcutaneous Silastic implants and rats were killed at 29 days of age. Northern blot analysis was used to measure AP prodynorphin, luteinizing hormone-beta (LH beta), follicle stimulating hormone-beta (FSH beta), and common alpha-subunit mRNA levels (normalized to 18S ribosomal RNA). Treatment groups (n = 5-6) consisted of control (CNT; empty implants), estradiol (E2; 4 days), E2 + progesterone (E2 + P4; 8 days and 4 days, respectively), and dihydrotestosterone (DHT; 4 days). Pituitary prodynorphin mRNA was significantly suppressed in only the DHT-treated animals (26 +/- 10% of CNT, p < 0.01). LH beta mRNA was suppressed by all steroid treatments (p < 0.01), FSH beta was lower in only the E2 group, and alpha-subunit was reduced in both the E2 + P4 and DHT groups (p < 0.01). Serum LH was suppressed by all steroid treatments but FSH was reduced in only the E2 and E2 + P4 groups (p < 0.01). Treatment of prepubescent rats with continuous high levels of gonadal steroids is known to severely reduce endogenous hypothalamic gonadotropin releasing hormone (GnRH) release and this is supported by our observation of reduced gonadotropin-subunit gene expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459343 TI - Ontogeny of apomorphine-induced stereotypy and its D1 and D2 receptor mediation in rats depleted of dopamine as neonates. AB - The ontogeny of apomorphine-induced stereotypy in rats treated with 6-OHDA (100 micrograms) or its vehicle on postnatal Day 3 was determined on Days 6, 21, or 60 90. Stereotypic sniffing and mouthing behavior were produced by apomorphine in control and DA-depleted animals as early as Day 6. Animals depleted of DA as neonates exhibited supersensitivity to these behavioral effects from Day 6 into adulthood. The relative contributions of D1 and D2 receptor activation to apomorphine-induced behaviors were determined by measuring the ability of specific D1 or D2 antagonists to block these effects in adults. Blockade of D1 receptors with SCH 23390 or D2 receptors with clebopride suppressed apomorphine induced stereotypy in both vehicle- and 6-OHDA-treated rats. However, adults depleted of DA as neonates were less sensitive to the DA antagonists than were control rats. These results demonstrate that apomorphine-induced stereotypy is present as early as postnatal Day 6. Rats depleted of DA as neonates continue to exhibit these behaviors, even at lower doses of apomorphine than were necessary in control animals. Finally, coactivation of D1 and D2 receptors appears necessary for apomorphine-induced stereotypy in both groups of rats. PMID- 1459344 TI - Thermogenesis during ultrasonic vocalization by rat pups isolated in a warm environment: a thermographic analysis. AB - Ultrasonic vocalizations, emitted by rat pups when separated from their mother, littermates, and home cage, have been used as a measure of isolation distress. Recently, we demonstrated that cold exposure is the primary component of isolation that induces the vocalization. We were unable, however, to suppress all ultrasound production when transferring pups to a thermoneutral (35 degrees C) environment. Using an infrared thermography system that allows us to estimate noninvasively heat production by brown adipose tissue, we found that pups transferred from the home nest to a 35 degree C test chamber exhibited sizable levels of heat production while they were vocalizing. Moreover, both heat production and ultrasound emission decreased over the 15-min test. Next, we used extreme care to minimize thermal, and therefore respiratory, stimulation of pups before, during, and after the transfer procedure. We found that such precautions prevented both heat production and ultrasound emission following transfer. These results indicate that infant rats' thermal sensitivities are far greater than previously suspected. PMID- 1459345 TI - Ultrasonic vocalization by rat pups during recovery from deep hypothermia. AB - Vocalization in the ultrasonic range (USV) has been reported to occur in young rodents in response to isolation, novelty, handling, and cold. Heretofore these calls have been known to occur only in alert, attentive, or emotionally aroused animals. These studies describe the emission of USV by comatose 9- to 10-day-old rat pups during recovery from deep hypothermia. Calling began at 15-18 degrees C core temperature while pups were virtually unresponsive to stimulation. Experimental results describe the patterns of call production in relation to respiration, cardiac function, colonic temperature, and brown adipose tissue thermogenesis. These vocalizations were 32-42 kHz in frequency, reached peak rates of 50/min at 23 degrees C, and were eliminated by laryngeal denervation, thus resembling isolation-induced vocalizations. However, contact with their dams failed to reduce call rates until pups had warmed above 25 degrees C. Newborn and weanling pups also emitted USV in deep hypothermia, but no USV were observed in pups recovering from general anesthesia. The possible functions and evolution of this behavior are discussed. PMID- 1459346 TI - Prenatal stress exposure alters postnatal behavioral expression under conditions of novelty challenge in rhesus monkey infants. AB - This prospective study investigated whether mild maternal stress during pregnancy could alter the behavioral and affective responses in rhesus monkey infants in a complex, novel environment. Twenty-four rhesus monkey infants were tested on three occasions at 6 months of age in a novel environment. Twelve infants were derived from mothers exposed to a daily 10-min mild stressor from Day 90 to Day 145 postconception, while 12 were derived from mothers undisturbed during pregnancy. Prenatally stressed infants demonstrated more disturbance behavior, and lower levels of gross motor/exploratory behavior. Moreover, half of the prenatally stressed infants showed an abnormal response, falling asleep, while none of the control infants displayed this behavior. Males exhibited more clinging to surrogates, while females spent more time in gross motor/exploratory behaviors, with prenatally stressed males tending to spend the least time in gross motor/exploratory activity. PMID- 1459347 TI - Protective effect of human pancreatic secretory trypsin inhibitor on cerulein induced acute pancreatitis in rats. AB - We examined the protective effect of human pancreatic secretory trypsin inhibitor (PSTI), a specific trypsin inhibitor secreted from pancreatic acinar cells into the pancreatic duct, on cerulein-induced acute pancreatitis in conscious rats. The protective effect of human PSTI-RS, an analogue of PSTI with Arg-44 to Ser substitution which has a longer half-life in vitro, was also examined. Intraperitoneal administration of a pharmacological dose of cerulein to conscious rats induced acute pancreatitis, characterized by light microscopy as cellular disorganization of the acini and interstitial edema. Intravenous infusion of human PSTI (10, 50 or 250 micrograms/rat/h) into rats with cerulein-induced acute pancreatitis decreased their pancreatic wet weight and plasma amylase concentration. It also caused a dose-dependent decrease in vacuoles in acinar cells and interstitial edema. Human PSTI-RS, which has a longer half-life in vivo, was more effective than native PSTI at the same dose rate (10 micrograms/rat/h) in reducing pancreatitis. These results suggest that human PSTI may have a beneficial effect on acute pancreatitis. PMID- 1459348 TI - Gallbladder emptying in patients with primary achalasia. AB - Being more evident that primary achalasia is not confined to the esophagus and that it may involve other organs in the digestive tract, gallbladder emptying was ultrasonographically evaluated in 10 patients affected with primary achalasia and in 10 controls. An intravenous cerulein infusion was used to induce gallbladder contraction. Eight out of 10 achalasic patients had a lower gallbladder emptying, and 6 out of 10 had a markedly delayed gallbladder emptying compared with the controls. Achalasic patients, taken as a whole, showed a significantly lower and delayed mean gallbladder emptying when compared with the controls. Such a finding confirms the possible extra-esophageal extension of primary achalasia. In this study, the hypothesis of impaired cholinergic gallbladder innervation in primary achalasia is discussed. PMID- 1459349 TI - E2 prostaglandins modulate cell proliferation in the small intestinal epithelium of the rat. AB - Groups of Sprague-Dawley rats were administered 1 mg/kg indomethacin subcutaneously, indomethacin subcutaneously plus 200 micrograms/kg oral 15-R-15 methyl-prostaglandin E2 (MePGE2) or oral MePGE2 twice daily for 10 days. The animals were treated with antibiotics to prevent mortality. Two control groups were used: control 1 was given placebo and control 2 was treated with antibiotics. All rats were killed 4 h after injection of a metaphase blocker, and the proliferative activity of the distal small intestine was examined in histological sections by means of the cumulative mitotic index (MI). A reduction in the number of villous cells was observed in the rats given antibiotics (p < 0.05 vs. control 1). The small intestinal villi of the rats treated with indomethacin had fewer cells than those of both control groups (p < 0.05) whereas the crypts contained more cells (p < 0.05) and had a higher MI than those of the controls (p < 0.05 vs. controls 1 and 2). These changes were reverted by the prostaglandin analogue. The number of cells of the small intestinal crypts and the cumulative MI in the rats who received indomethacin and the prostaglandin analogue were similar to controls, and they were significantly lower than the values observed in the animals treated with indomethacin (p < 0.05). The animals treated with the prostaglandin analogue and placebo developed a marked hyperplasia of the small intestinal villi (p < 0.05 vs. both control groups), but the atrophy of the villi induced by indomethacin was not prevented by simultaneous administration of the analogue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459350 TI - Life events and daily stress in duodenal ulcer disease. A prospective study of patients with active disease and in remission. AB - Life events and daily stress were assessed in patients with duodenal ulcer, active or in remission, and in matched disease and normal controls. The mean positive life event scores were significantly lower in duodenal ulcer patients than in disease and healthy controls, and lower in patients with active ulcer than in those in remission. The positive scores and total life change scores decreased significantly after 6 months in the control groups and showed no significant variation in the duodenal ulcer group after 6 months. We conclude that the perception of life events, especially positive ones, is associated with duodenal ulcer. PMID- 1459351 TI - pH-dependent secretion of gastrin in duodenal ulcer disease: effect of suppressing Helicobacter pylori. AB - Patients with duodenal ulcers and Helicobacter pylori infection have elevated plasma gastrin concentrations which fall after suppression of the organism. This may be due to H. pylori elevating the pH of the antral mucous layer, therefore preventing luminal acid from inhibiting gastrin release. To test this idea, we measured the plasma gastrin concentrations under basal conditions and in response to 4% peptone when the gastric lumen was maintained at pH 2.5 and at pH 5.5 by gastric perfusion. We studied 11 duodenal ulcer patients before and after suppression of H. pylori. Gastrin concentrations were significantly higher before suppression of H. pylori than after treatment in all three states; basal gastrin (pmol/l) fell from 9.2 (3.7-23, median and range) to 5.1 (1.7-15) after treatment; from 11.3 (3.8-29) to 5.9 (5.7-6.1) at pH 2.5 and from 15.2 (3.9-32) to 7.15 (6.1-14) at pH 5.5. The ratio of peptone-stimulated gastrin at pH 2.5/pH 5.5 was similar before (0.8; 0.5-1.7) and after (0.8; 0.5-1.1) suppression of H. pylori. These results indicate that infection with H. pylori increases basal and peptone-stimulated plasma gastrin concentrations, and that this response is independent of luminal pH. PMID- 1459352 TI - Sexual dysfunction amongst women with Crohn's disease: a hidden problem. AB - The sexual problems of 50 women with Crohn's disease, of whom 45 had a stable relationship, were investigated by structured interview and compared with age matched controls. Twenty-four percent patients had either infrequent or no intercourse compared with 4% of controls (chi 2 = 8.3, p < 0.005). However, amongst patients and controls who were sexually active, the frequency of intercourse was similar. Reasons for sexual inactivity included abdominal pain (24%), diarrhoea (20%) and fear of faecal incontinence (14%). Dyspareunia was common in patients (chi 2 = 6.5, p < 0.01) and this was irrespective of the site of disease (large vs. small bowel chi 2 = 0.85, NS). Women with perianal disease and fistulae were more likely to have dyspareunia than women with neither (chi 2 = 4.2, p < 0.05), although this was not so for less extensive involvement with only perianal disease (chi 2 = 2.8, NS) or fistulae (chi 2 = 0.8, NS). Vaginal candidiasis was more common in patients (chi 2 = 5.8, p < 0.02), and on occasions this may have contributed to dyspareunia. Women with Crohn's disease experience sexual problems much more than healthy controls and they need support, sympathetic investigation and management. PMID- 1459353 TI - The integrated response of the cardiovascular system to food. AB - To obtain information about the integrated response of the cardiovascular system to food, cardiac output and regional blood flow (superior mesenteric artery, renal artery and calf blood flow) were measured in 14 normal young healthy subjects after an overnight fast and following a standard 800-kcal meal. Results were compared with 8 subjects who remained fasted throughout the study. Cardiac output increased from a mean (SEM) fasting value of 4.8 (0.3) l/min to a peak after 30 min of 6.1 (0.5) l/min (p < 0.001). Superior mesenteric blood flow increased from a fasting value of 463 (45) to a peak of 854 (110) ml/min also after 30 min (p < 0.001). These changes were accompanied by a significant fall in both systemic vascular resistance and superior mesenteric vascular resistance (p < 0.001). Only at the 15-min postprandial measurements was there a significant relationship between the increase in cardiac output and superior mesenteric artery blood flow (r = 0.62, p = 0.02). Calf blood flow increased and vascular resistance fell postprandially (p < 0.05), but there was little change in right renal artery blood flow. There was an insignificant fall in renal vascular resistance. Heart rate increased from a resting value of 65 (3) to a peak of 77 (4) beats/min after 15 and 30 min (p < 0.001), diastolic blood pressure fell postprandially with little change in systolic blood pressure. These results suggest that in healthy young subjects the increase in gut blood flow is met by an increase in cardiac output, with little evidence of redirection from other vascular beds. The early postprandial increase in superior mesenteric blood flow may account for the increase in cardiac output, although the magnitude of the change is much greater for cardiac output than superior mesenteric artery blood flow. PMID- 1459354 TI - Medical therapy of Menetrier's disease with omeprazole. AB - Medical therapy of Menetrier's disease is often unsatisfactory and may lead to surgical treatment. Two cases, previously unresponsive to H2 antagonists, are presented showing a marked response to omeprazole. PMID- 1459355 TI - Irritable bowel syndrome: can the patient's response to colonoscopy help with diagnosis? AB - The irritable bowel syndrome (IBS) is a common disorder estimated to affect up to 20% of adult Caucasians, with only a small percentage requiring investigation. This prospective study was performed to substantiate the impression that patients with IBS experience more pain during endoscopic examination of the colon than do patients with other conditions. Patients with IBS were observed to experience significantly more pain during colonoscopy than did patients without IBS (median observed pain scores 46 and 9, respectively), p < 0.001. The intensity of the pain perceived during examination was significantly higher for patients with IBS than for those without IBS (median 52.5 and 23.5, respectively), p < 0.001. Within the groups, there was no significant difference between flexible sigmoidoscopy and colonoscopy in observed or perceived pain. 64% of the patients with IBS said that the pain experienced at colonoscopy was identical to their presenting pain. This study supports the hypothesis of a lower colonic pain threshold with colonic hyperalgesia in patients with IBS. We have found that hypersensitivity to the endoscopic examination of the colon is a useful clinical adjunct in the diagnosis of the IBS in those selected to undergo colonoscopy. PMID- 1459357 TI - Increased concentrations of synovial-type phospholipase A2 in serum and pulmonary and renal complications in acute pancreatitis. AB - The most important fatal complications of acute pancreatitis are respiratory dysfunction and anuria. Phospholipase A2 has been postulated to be associated with pathologies of various diseases, such as acute pancreatitis, septic shock and multiple injuries. We have recently developed immunoassays for the measurement of pancreatic and nonpancreatic synovial-type phospholipase A2. The present prospective study on 35 consecutive patients with acute pancreatitis indicated that the concentration of synovial-type phospholipase A2, the catalytic activity of phospholipase A2 and the concentration of C-reactive protein in serum were significantly higher in those patients suffering from acute pancreatitis who needed respirator treatment than in those who managed with spontaneous breathing, while there was no difference between these groups in the concentration of pancreatic phospholipase A2. The only significant difference between patients whose highest creatinine concentration rose up to 140 mumol/l and those whose highest creatinine concentration remained below this cutoff value was in their synovial-type phospholipase A2 values. The increased concentration of nonpancreatic synovial-type phospholipase A2 in serum was associated with pulmonary and renal complications. These results emphasize the role of synovial type phospholipase A2 in the pathophysiology of acute pancreatitis. PMID- 1459356 TI - Lack of effect of synthetic human gastric inhibitory polypeptide and glucagon like peptide 1 [7-36 amide] infused at near-physiological concentrations on pentagastrin-stimulated gastric acid secretion in normal human subjects. AB - Gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 [7-36 amide] (GLP-1) are glucose-dependent insulinotropic gut hormones. Under experimental conditions, both have been shown to reduce stimulated gastric acid secretion. To study their individual and combined effects on pentagastrin-stimulated (0.1 micrograms/kg/h from -90 to 120 min) gastric volume, acid and chloride output, on separate occasions, synthetic human GIP (1 pmol/kg/min) and/or GLP-1 [7-36 amide] (0.3 pmol/kg/min) or placebo (0.9% NaCl with 1% albumin) were infused intravenously (from -30 to 120 min) in 9 healthy volunteers. At 0 min, a glucose infusion was started that mimicked the glycemic profile after an oral glucose load of 50 g/400 ml and allowed for the glucose-dependent insulinotropic action of GIP and GLP-1 [7-36 amide]. Pentagastrin stimulated acid output significantly, but neither GIP nor GLP-1 [7-36 amide] either alone or in combination, reduced pentagastrin-stimulated gastric acid secretion. The circulating concentrations of GIP and GLP-1 [7-36 amide] obtained at steady state during exogenous administration of synthetic peptides were similar to or higher than those reached after oral glucose (endogenous secretion). In conclusion, (penta)gastrin stimulated gastric acid secretion is not inhibited by physiological circulating concentrations of GIP or GLP-1 [7-36 amide]. Therefore, the insulinotropic action of these intestinal hormones is physiologically more important than their possible role as enterogastrone. PMID- 1459358 TI - The mammalian anti-alpha-smooth muscle actin monoclonal antibody recognizes an alpha-actin-like protein in planaria (Dugesia lugubris s.l.). AB - The presence of an alpha-smooth muscle (alpha-sm) actin-like protein in planaria (Dugesia lugubris s.l.) is reported. The protein shows a 42 kDa molecular weight determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis and is specifically recognized by the mammalian anti alpha-sm actin monoclonal antibody. When a planarian is induced to regenerate by head amputation, the immunostaining of the alpha-sm actin-like molecule becomes important in the area of growing blastema, reaching a maximum between 70-120 hours after injury. Conventional electron microscopy at the 4-day-regeneration stage shows that blastema-forming cells are a homogeneous population whose morphological features resemble those of migrating mesenchyme-like cells; only the myoblasts show a recognizable phenotype. The immunocytochemical localization of alpha-sm actin-like molecule by immunoperoxidase (light microscopy) and immunogold stains (electron microscopy) was carried out on both intact and injured worms. The antigen was localized mainly at the basal portion of the epidermal cells and in the undifferentiated mesenchyme-like cells. Myoblasts, but not differentiated myofibers, were also labelled by this antibody. The results indicate that in the lower Eumetazoan planarians, as well as in vertebrates, the alpha-sm actin can be considered to be a marker for myoid differentiation. The suggestion that alpha-sm actin can be used as a marker for mesenchyme-like cells in vertebrates and in invertebrates is also discussed. PMID- 1459359 TI - Identification of plakoglobin in oocytes and early embryos of Xenopus laevis: maternal expression of a gene encoding a junctional plaque protein. AB - We have isolated a cDNA encoding the junctional plaque protein plakoglobin of Xenopus laevis and determined its amino acid sequence. Comparisons with sequences of related proteins of the same and other species revealed that in Xenopus plakoglobin and beta-catenin are two different proteins, encoded by separate genes, that both genes are expressed in embryogenesis, and that the amphibian plakoglobin is more closely related to the human plakoglobin than to beta-catenin of the same species. Using this cDNA as a probe, we also show that plakoglobin mRNA is produced and stored in Xenopus oocytes and eggs. We discuss the possibility that the maternal pool of this junctional protein contributes to the junctional structures connecting the oocyte with the follicle epithelium and to the rapid formation of desmosomes and other plaque-bearing junctions in pregastrulation embryogenesis. PMID- 1459360 TI - Time dependency of 1,25(OH)2D3 induction of calbindin mRNA and calbindin expression in chick enterocytes during their differentiation along the crypt villus axis. AB - Quantitative methods of in situ hybridization and immunocytochemistry have been used to measure 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) induction of calbindin mRNA and calbindin protein expressed in jejunal enterocytes at all points along the crypt-villus axis over a 24 h period. Small amounts of calbindin mRNA detected in vitamin D3 deficient (D-deficient) chick intestine increased rapidly to maximal values 8 h after hormone injection. The magnitude of this response was inversely related to age of enterocyte measured separately by injecting tritiated thymidine into D-deficient and 1,25(OH)2D3-injected birds. Enterocytes of all ages expressed small amounts of calbindin 3 h after hormone injection. This amount of calbindin then increased up to 24 h after hormone injection. Maximal calbindin expression took place in basal villus enterocytes. Later decrease in the ability of upper villus enterocytes to express calbindin was associated with a similar fall in calbindin mRNA expression. Previously it was suggested that inefficient translation to calbindin mRNA might take place in basal villus enterocytes 48 h after vitamin D injection. Present work using 1,25 (OH)2D3 shows that calbindin expression takes place at a constant rate during this early stage of enterocyte development. Secondary events limiting higher rates of calbindin synthesis in upper crypt and basal villus enterocytes remain to be identified. PMID- 1459361 TI - The chromatin structure of the mouse beta-2-microglobulin locus. AB - Within the promoter regions of both major histocompatibility complex (MHC) class I genes and the beta 2-microglobulin (beta 2m) gene, there are a number of common regulatory elements suggesting co-ordinate control. However, there is also evidence to suggest that beta 2m and class I are differentially regulated, indicating that these genes may have distinct regulatory elements. We sought to explore this question by analysing DNase I hypersensitive (DH) sites flanking the beta 2m gene. Five DH sites have been found within the vicinity of the beta 2m gene. One of these sites (DH1) located within the promoter region, correlates with the transcriptional activity of beta 2m since it is weak in embryonal (beta 2m negative) cell lines. The remaining DH sites (2-5) are located downstream of the beta 2m gene. The most proximal downstream site, (DH2) located 5.5 kb from the last exon, was observed only in embryonal cell lines, indicating possible involvement in the downregulation of beta 2m. Furthermore, this site is markedly diminished in differentiated F9 cells. Possible roles for the remaining sites are discussed, in particular relationship to a second transcriptional unit identified in the vicinity. In addition, a similar analysis reveals a cluster of DH sites located downstream from the last exon of the human beta 2m gene. PMID- 1459362 TI - Ontogenesis of the murine hepatic extracellular matrix: an immunohistochemical study. AB - To define the role of the extracellular matrix (ECM) in hepatogenesis, we examined the temporal and spatial deposition of fibronectin, laminin and collagen types I and IV in 12.5-21.5 day fetal and 1, 7 and 14 day postnatal rat livers. In early fetal liver, discontinuous deposits of the four ECM components studied were present in the perisinusoidal space, with laminin being the most prevalent. All basement membrane zones contained collagen type IV and laminin, including those of the capsule (mesothelial), portal vein radicles and bile ductules. Fibronectin had a distribution similar to that of collagen type IV early in gestation. However, at later gestational dates, fibronectin distribution in the portal triads approached that of collagen type I, being present in the interstitial connective tissues; whereas, collagen type IV and laminin were restricted to vascular and biliary basement membrane zones in those regions. The cytoplasm of some sinusoidal lining cells and hepatocytes reacted with antibodies to extracellular matrix components. By electron microscopy the immunoreactive material was localized in the endoplasmic reticulum, indicating the ability of these cells to synthesize these ECM proteins. Biliary ductular cells had prominent intracytoplasmic staining for laminin and collagen type IV from day 19.5 gestation until 7 days of postnatal life, but lacked demonstrable fibronectin or collagen type I. These results demonstrate that by 12.5 days of gestation the rat liver anlage has deposited a complex extracellular matrix in the perisinusoidal space. The prevalence of laminin in the developing hepatic lobules suggests a possible role for this glycoprotein in hepatic morphogenesis. In view of the intimate association of the hepatic lobular extracellular matrix with the developing vasculature, we hypothesize that laminin provides a scaffold of the developing liver, but once the ontogenesis is complete, intrahepatic perisinusoidal laminin expression is suppressed. PMID- 1459363 TI - Cytoplasmic events in human meiotic arrest as revealed by immunolabelling of spermatocyte proacrosin. AB - Proacrosin appears in the Golgi complex as early as the mid-pachytene stage and immediately thereafter initiates partition to be equally distributed in spermatids. The anti-proacrosin monoclonal antibody 4D4 (mAb 4D4) was used as a marker of these cytoplasmic events in ten men exhibiting spermatogenesis arrest in three specific stages: (i) leptotene/zygotene spermatocyte I with impaired chromosome pairing (six cases), (ii) early pachytene I (one case) and (iii) metaphase/anaphase I (three cases). Prophase arrest stages were identified on testis sections stained by silver nitrate. MAb 4D4 labelling revealed two types of leptotene/zygotene arrest depending on whether proacrosin was expressed or not. The data obtained enabled us to distinguish between: (i) nuclear blockages due to chromosome and/or nuclear matrix anomalies, when cytoplasmic events were either inhibited or not inhibited, and (ii) nuclear anomalies due to microtubular disturbances. In this latter case, cytokinesis was impaired as early as the prophase I, thus indicating a relationship between the Golgi partitioning and the microtubule network. Data show that meiotic arrest investigations, by means of an appropriate marker of the cytoplasmic events, provide valuable information on spermatogenic developmental processes. PMID- 1459364 TI - Reducing the number of rabbits in the low-volume eye test. AB - Although the Draize eye irritation test has provided important and useful information for eye safety assessments, considerable effort has been directed toward refining the assay procedure, reducing the number of animals used, and replacing this assay with alternative methods. The low-volume eye test (LVET) is a refinement of the Draize eye irritation test that uses 1/10 the volume of test substance placed directly on the cornea. The level and duration of eye irritation in the LVET are less than those in the Draize procedure, which means that it is a less stressful test. Furthermore, LVETs are more predictive of human response. Statistical studies have been conducted to determine the effects of reducing the number of animals used in the Draize test. These results suggested that a three animal test would provide essentially the same information as the six-animal test. A similar analysis has not been performed on results from the LVET. Accordingly, the present study was undertaken to evaluate previously existing LVET data to determine if the number of animals used in a LVET can be decreased as has been shown for the Draize test. The results of the analysis are consistent with the findings of earlier evaluations of classical Draize data. Three-animal subsets from 119 six-animal LVETs provided the correct classification greater than 92% of the time for three different classification schemes. Furthermore, the discrepancies between the three-animal subsets and the six-animal maximum average score tended to be smaller than those observed for the Draize test.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459365 TI - Adduction of hemoglobin and albumin in vivo by metabolites of trichloroethylene, trichloroacetate, and dichloroacetate in rats and mice. AB - Adducts to macromolecules from trichloroethylene formed by in vivo and in vitro metabolism have been reported by many investigators. We examined the in vivo adduction of the blood proteins hemoglobin (Hb) and albumin in rats and mice dosed orally with [14C]trichloroethylene ([14C]TRI) to explore the development of a protein adduct biomarker of TRI exposure. We also examined the adduction of these two proteins from doses of [14C]trichloroacetate (TCA) and [14C]dichloroacetate (DCA), two metabolites of TRI. Association of label with albumin peaked at 4-8 hr in the rat (2480 nmol eq TRI/mg protein) and 2-4 hr in the mouse (1580 nmol eq TRI/mg protein). The decay was exponential with a half life consistent with that of rat or mouse albumin (approx 24 hr). The time course of label with Hb was characterized by an early plateau at 8 hr in rat (28 nmol eq TRI/mg protein), 4 hr in mouse (7 nmol eq TRI/mg protein), and followed by a slow steady increase, peaking at 120 hr (54 nmol eq TRI/mg protein, rat; 38 nmol eq TRI/mg protein, mouse). This apparent binding was linear with dose in the rat, but was convex in the mouse albumin (mouse Hb label was below detection at low dose). We also found that a portion of the irreversibly associated label, referred to by previous investigators as "binding," could be accounted for as metabolic incorporation of label into glycine and serine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459366 TI - The action of chelating agents in experimental uranium intoxication in mice: variations with structure and time of administration. AB - The determination of the relative abilities of 11 chelating agents to enhance the urinary and fecal excretion of uranium when administered 10 min after uranyl acetate dihydrate (UAD) in mice showed that the most effective of these were Tiron, desferrioxamine, and 1,2-dimethyl-3-hydroxypyrid-4-one. An increase in the interval between UAD administration and that of the chelating agent drastically reduces the net mobilization of the uranium by the chelating agents examined. When given shortly after UAD, Tiron produced the greatest reduction in renal and bone levels of uranium. None of the chelating agents were able to affect the bone levels of uranium when administered 24 hr or more after the administration of the UAD. PMID- 1459367 TI - Pulmonary toxicity of inhaled polypropylene fibers in rats. AB - This study was initiated to assess the pulmonary toxicity of a polyolefin fiber composed of polypropylene in male Fischer 344 rats after 90 days of inhalation exposure. To increase fiber respirability in the rodent, polypropylene fibers were size-selected before aerosolization to have a geometric mean diameter of 1.6 microns (46% < 1 micron) and a geometric mean length of 30.3 microns. Three groups of animals were exposed in nose-only inhalation chambers, 6 hr/day, 5 days/week, for 90 days to 15, 30, or 60 mg/m3 of polypropylene, or filtered air (negative control). Microscopic examination of the polypropylene fiber-exposed lungs revealed that, at all time points examined in the study, there was a dose dependent increase in pulmonary macrophages. These minimal or mild increases in cellularity appeared to be reversible, especially at the lower doses 30 days post exposure. No fibrosis was observed in any of the groups. A strong correlation was found between the external exposure concentration, the time of exposure, and the lung fiber burden. The number of partially degraded (segmented) fibers within the lung increased with the exposure concentration and period of exposure, as well as with the period of recovery after termination of exposure at 90 days. Fibers were recovered from exposed lungs using a hypochlorite digestion technique. PMID- 1459368 TI - The effect of exposure pattern on the accumulation of particles and the response of the lung to inhaled particles. AB - We hypothesized that a rapid rate of delivery of particles to the lung would overwhelm the normal clearance mechanisms of the lung and result in a higher lung burden of particles and a greater inflammatory response than a slower rate of particle delivery. F344/N rats were exposed over a 12-week period to the same weekly concentration times time product of carbon black (CB) particles, but at three different exposure rates: 3.5 mg/m3, 16 hr/day, 7 days/week; 13 mg/m3, 6 hr/day, 5 days/week; or 98 mg/m3, 4 hr/day, 1 day/week. The intermediate exposure rate was chosen to mimic an occupational work week and to give an 8-hr, time weighted average exposure equal to the threshold limit value (TLV) for nuisance dusts of the American College of Governmental Industrial Hygienists (10 mg/m3). Pure CB has a lower TLV, 3.5 mg/m3, than nuisance dusts, but this is based on avoidance of excessive dirtiness in the workplace, not on the toxicity of CB. Lung burdens of CB were measured after 3, 6, 9, and 12 weeks of exposure and at 4, 8, 12, 16, and 24 weeks after the exposure ended. The inflammatory response was quantified by analysis of bronchoalveolar lavage fluid (BALF) after 6 and 12 weeks of exposure and at 1, 12, and 24 weeks after exposure. The histopathology of the lung was evaluated at the end of the exposure and at 24 weeks after the exposure. Acquired lung burdens were between 3 and 4 mg/lung at the end of the exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459369 TI - Quantitation of paraquat in biological samples by radioimmunoassay using a monoclonal antibody. AB - We have developed a sensitive and specific radioimmunoassay for the quantitative determination of paraquat in plasma, urine, and bronchoalveolar lavage fluid using a monoclonal antibody. The synthesis of the iodinated paraquat tracer is novel and less complicated than a previously reported method. Regardless of the type of biological sample analyzed, the sensitivity of the assay was 0.46 ng/ml in a 200-microliters aliquot. The results correlated well with those of another assay performed in a separate laboratory. Paraquat concentrations were determined in plasma and in urine of a dog over several days after the intravenous administration of 7.48 mg paraquat cation/kg and in bronchoalveolar lavage fluid obtained 34 hr after the 2-hr infusion was discontinued. Concentrations of paraquat measured ranged from 14.1 to 0.03 micrograms/ml in plasma and 2034 to 0.36 micrograms/ml in urine. Concentrations of paraquat in plasma obtained at various times after the ingestion of paraquat by three patients ranged from 51.0 to 0.010 micrograms/ml. PMID- 1459371 TI - Relative bioavailability of lead from mining waste soil in rats. AB - The purposes of this study were to determine the extent of absorption of lead (Pb) in mining waste soil from Butte, Montana, and to investigate the effect of mining waste soil dose (g soil/day) on tissue lead concentrations. Young, 7- to 8 week-old male and female Sprague-Dawley rats (5/sex/group) were given mining waste soil that contained 810 or 3908 ppm lead mixed in a purified diet (AIN-76) at four different dose levels (0.2, 0.5, 2, and 5% dietary soil) for 30 consecutive days. Standard groups included untreated controls and dosed feed soluble lead acetate groups (1, 10, 25, 100, and 250 micrograms Pb/g feed). The test soil dose levels bracketed a pica child's soil exposure level and the lead acetate concentrations bracketed the test soil dose levels of lead. Liver, blood, and femur were analyzed for total lead concentration using graphite furnace atomic absorption spectroscopy. Clinical signs, body weight, food consumption, and liver weights for test soil and standard groups were similar to control. Tissue lead concentrations from test soil animals were significantly lower than the tissue concentrations for the lead acetate group. Relative percentage bioavailability values, based on lead acetate as the standard, were independent of the two different test soils, dose levels, and sex and were only slightly dependent on the tissue (blood > bone, liver). Mean relative percentage bioavailability values of lead in the Butte mining waste soil were 20% based on the blood data, 9% based on the bone data, and 8% based on the liver data. The results of this study will provide the information needed to determine the significance of lead exposure from Butte soils in assessing human health risks as part of the Superfund Remedial Investigation/Feasibility Study process. PMID- 1459370 TI - Neuropathologic findings in young male rats in a subchronic oral toxicity study using triethyl lead. AB - This study was undertaken to ascertain the neuropathologic effects of low level exposure of triethyl lead (3EL) to young male rats. Groups of 20 male Sprague Dawley weanling rats were given 3EL at 0, 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for 91 days, 5 days/week by oral gavage. Lead acetate (PbHOAC) was given at 200 mg/kg body wt/day as a positive control. Animals (five or six) were perfused with glutaraldehyde following barbiturate anesthesia at the termination of the experiment. These animals and the remaining members of the group received a thorough gross and microscopic postmortem examination. Sections of the central, peripheral, and autonomic nervous systems were examined and lesions scored. No lesions were noted in the brain, but randomly distributed light microscopic changes of spinal cord Wallerian degeneration were noted to increase in a dose responsive manner (rho = 0.48; p < 0.01), with 3EL administration. Ultrastructural examination of selected sections of the lumbosacral nerves, revealed lesions characterized by reduced neurofilaments and neurotubules, and irregular lamellated axoplasmic dense bodies in all animals receiving lead. Organolead was only detected in animals receiving 3EL, but lead cations were detected in all lead-treated animals. The brain lead levels of 1.00 mg/kg/day and 200 mg Pb acetate positive control animals were equivalent. As distinctive ultrastructural lesions were seen in all rats treated with 3EL, we suggest that the no observed adverse effect level (NOAEL) for 3EL be lowered to less than 0.05 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459372 TI - Gonadal effects of fetal exposure to the azo dye congo red in mice: infertility in female but not male offspring. AB - The present study describes the relationship between gonadal agenesis and fertility in male and female mice exposed in utero to the diazo dye Congo red (CR). Maternal CR treatment inhibited testicular and ovarian function in the offspring after oral administration of 1 or 0.5 g/kg/day on Gestational Days 8 12. The testes of male offspring from CR-exposed dams were small in size and contained hypospermatogenic seminiferous tubules. However, despite the fact that testis weight was reduced by more than 70% in some males, they displayed normal levels of fertility when mated to untreated females for over 10 months. In contrast, female offspring from CR-exposed dams produced only about half as many litters and pups as the control pairs did under long-term mating conditions. Histological examination of the ovaries revealed that subfertility was correlated with ovarian atrophy. Females lacking maturing follicles were considerably less productive (1.3 litters and 11.5 pups) than treated females with histologically normal ovaries (7.1 litters and 78.1 pups). In summary, prenatal exposure to the dye CR affects the gonads of both male and female offspring, but only the female offspring display reduced fertility. PMID- 1459373 TI - Toxicity and carcinogenicity studies of quercetin, a natural component of foods. AB - Quercetin is a naturally occurring chemical found in our daily diet in fruits and vegetables. Toxicity and carcinogenicity studies of quercetin were conducted in male and female F344/N rats, under conditions which allowed comparison to results of approximately 400 previously tested chemicals. The chemical was administered in the feed for 2-years at concentrations of 0, 1000, 10,000, or 40,000 ppm, and the estimated dose delivered was approximately 40-1900 mg/kg/day. There were no treatment-related effects on survival and no treatment-related clinical signs of toxicity. The high-dose groups had reduced body weight gain in comparison to controls during the last half of the study. At interim evaluations at 6 and 15 months, treatment-related toxic lesions were not observed, but at 2 years toxic and neoplastic lesions were seen in the kidney of male rats, including increased severity of chronic nephropathy, hyperplasia, and neoplasia of the renal tubular epithelium. Under the conditions of these 2-year studies quercetin showed carcinogenic activity in the kidney of the male rat, causing primarily benign tumors of the renal tubular epithelium. Quercetin did not cause tumors at other sites. Quercetin is a genotoxic chemical, but the neoplastic response observed in the kidney may be due in part to a combination of nongenotoxic and genotoxic events. PMID- 1459374 TI - Examination of the local lymph node assay for use in contact sensitization risk assessment. AB - The purpose of this study was to evaluate the utility of the murine local lymph node assay (LLNA) for contact sensitization risk assessment. Cellular proliferative activity in draining lymph nodes was determined for individual animals on Day 5 following four daily epicutaneous applications of the test chemical to the ears. Seventeen chemicals were tested, covering a range of materials including preservatives, drug actives, and perfume raw materials. The assay was found to be useful for identifying strong, moderate, and some weak sensitizers as defined by other testing methods (guinea pig, human). For evaluating the antigen specificity of the LLNA proliferative response, an in vitro blastogenesis assay was used. Dendritic cells (DC) isolated from lymph nodes of mice treated 24 hr earlier with trinitrochlorobenzene (TNCB) were capable of in vitro stimulation of lymphocytes from TNCB-sensitized mice, but not lymphocytes from mice sensitized to the preservative mixture of 5-chloro-2 methylisothiazolinone plus 2-methylisothiazolinone (MCI/MI). Conversely, DC from mice treated 24 hr earlier with MCI/MI were capable of stimulating lymphocytes from MCI/MI-sensitized mice, but were unable to stimulate lymphocytes from TNCB sensitized mice, demonstrating the specificity of the response. The results of these studies support the use of the murine LLNA for both investigative and predictive contact sensitization testing. The LLNA offers the advantages of requiring less time for completion, incorporating an objective endpoint, requiring approximately half the number of animals, and being less costly than most currently employed guinea pig test methods. In addition, we believe the murine LLNA is a useful test to incorporate into a scheme for contact sensitization risk assessment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459375 TI - Alkoxyresorufin metabolism in white-footed mice at relevant environmental concentrations of Aroclor 1254. AB - Recent investigations have detected polychlorinated biphenyl (PCB) body burdens in wild white-footed mice (Peromyscus leucopus) captured at hazardous waste sites. Insufficient information is currently available to interpret the toxicological significance of these body burdens. In an effort to provide this information, we investigated hepatic changes and PCB body burdens in white-footed mice following a 21-day dietary exposure to a PCB mixture, Aroclor 1254. Dietary concentrations tested were 0, 2.5, 25, 50, and 100 mg Aroclor 1254/kg diet (reported as ppm). Liver weights were significantly increased at all concentrations except 2.5 ppm. Ethoxyresorufin O-dealkylase (EROD) activity, an aryl hydrocarbon hydroxylase-type substrate, was significantly increased at all PCB concentrations, but the dose-response tended to plateau above 25 ppm. Pentoxyresorufin O-dealkylase (PROD) activity, a putative phenobarbital-type substrate, was significantly increased in a dose-dependent manner at 25 ppm PCB and above, with no plateau response. Pentobarbital sleep time was significantly decreased at 25 ppm, but not at 2.5 ppm. Results indicate white-footed mice undergo a mixed-type induction pattern following exposure to Aroclor 1254, with EROD the most sensitive indicator of PCB exposure. This investigation identified a no observed effect concentration for liver weights and PROD activity at 2.5 ppm in the diet which is equivalent to a body burden of 2.0 mg Aroclor 1254/kg wet wt of mice; the no observed effect concentration for EROD is below these levels. These results support the use of EROD, PROD, and liver weight as biomarkers of PCB exposure in field-captured rodents. PMID- 1459376 TI - Neurobehavioral effects from acute exposures to methyl isobutyl ketone and methyl ethyl ketone. AB - Subjects were tested for neurobehavioral performance in an environmental chamber to detect the presence of subclinical central nervous system effects from 4-hr exposures to methyl isobutyl ketone (MIBK) at 100 ppm, methyl ethyl ketone (MEK) at 200 ppm, MIBK at 50 ppm with MEK at 100 ppm, or a placebo (i.e., a 5-min presentation of 25 ppm MEK-MIBK at each exposure period outset). Subjects were 68 males and 75 females recruited from local universities; ages ranged from 18 to 32 years. Ethanol by ingestion (95%-0.84 ml/kg) was used as a positive control. Five psychomotor tests (choice reaction time [CRT], simple reaction time [SRT], visual vigilance, dual task [auditory tone discrimination and tracking], memory scanning), one sensorimotor test (postural sway), and a test of mood (profile of mood states) were used to measure neurobehavioral effects. Additionally, chemical measurements (blood and breath) and reports of sensory and irritant effects were measured. The chemical exposures produced statistically significant performance effects on only 4 of 32 measures (% correct responses-visual vigilance, movement time-CRT, SRT, % incorrect responses-dual task). These effects, however, were not substantial and could not be attributed directly to the chemical exposures. Alcohol ingestion, however, produced significant decrements on every performance test except memory scanning and mood. An interaction occurred between gender and alcohol ingestion, such that more statistically significant performance decrements were found for females than for males. Significant odor sensations and irritant effects were reported by the subjects during the chemical exposures. The MEK results agree with earlier MEK experiments at comparable exposure conditions, and the MIBK results are consistent with a recent Swedish study that used MIBK exposures and showed no significant behavioral performance decrements from single MIBK exposures at 50 ppm with 50 W exercise. Additionally, the MIBK-MEK combination exposure showed no evidence of any interaction effects on either the behavioral or chemical measurements. The principal effects resulting from exposures to MEK and MIBK at the durations and concentrations used in the study are limited to sensory and irritant effects. PMID- 1459377 TI - Behavioral development following daily episodes of mother-infant separation in the rat. AB - Use of dermal or inhalation routes of maternal exposure during the postnatal period in rodent developmental neurotoxicity evaluations would be most practical if dams could be separated from their pups during the exposure period. However, this procedure raises questions concerning the effects of mother-infant separation itself on neurotoxicity endpoints. In the present study, Sprague Dawley rat pups were either maternally deprived in warm incubators for 6 hr each day (7:00 AM-1:00 PM) or left with their dams (control), from Postnatal Day 4-20 (PND4-20), and were tested on a range of endpoints commonly used in developmental neurotoxicology. These included motor activity (PND13, 17, 19, 21, 29, 60), olfactory learning (PND18) and retention (PND25), T-maze delayed alternation (PND23, 24), acoustic startle response (PND23, 62), and auditory thresholds (PND62). None of the behavioral measures were affected by daily separation. Apparently, interrupting the mother-infant interaction for 6 hr/day has little or no effect by itself on behavioral development, as assessed by these measures. PMID- 1459378 TI - Diagnosis, antibiotic treatment and outcome of acute tonsillitis: report of a WHO Regional Office for Europe study in 17 European countries. AB - The diagnostic and prescribing habits of general practitioners from 17 European countries for 4094 patients with acute tonsillitis were assessed, and differences in outcome were identified. At least 10 general practitioners from each country filled in a questionnaire for each episode of acute tonsillitis treated during a three month period, November 1989-May 1990. Differences in days of fever and illness were tested by one-way analysis of variance. Bacteriological tests were rarely used for diagnosis in East Germany, Poland and the Netherlands, while a high percentage (70-96%) occurred in Turkey, Romania, Israel, Yugoslavia, Finland and Greece. Group A beta-haemolytic streptococci (40 per cent) and a negative test result (43 per cent) were the most common results. Ninety per cent or more patients were treated with an antibiotic. Oral penicillin was especially prescribed in the northern countries of Europe and parenteral penicillin in southern Europe. For almost all countries the mean number of days with fever was between 2 or 3 days. The mean number of days with illness differed greatly (F = 62.12; P = 0.0000). Turkey had the lowest mean (2.56), while Poland had the highest mean (8.23). PMID- 1459379 TI - Fever in general practice. I. Frequency and diagnoses. AB - Although fever is a common symptom, few studies have broadly addressed this as a clinical problem in general practice. The aims of this study were to determine the frequency of fever among general practice patients in two rural municipalities in Norway, the diagnoses (according to ICHPPC-2-def.) of conditions causing fever, and the receptionist's role in the management of these problems. All the general practitioners and their receptionists within the study area participated. During 4 weeks throughout 1988 all individuals attending their general practitioner had their body temperature measured with an electronic thermometer (orally > or = 7 years, rectally < 7 years). Fever was defined as an oral body temperature > or = 37.5 degrees C (rectally > or = 38.0 degrees C in those < 7 years). All telephone applications, including telephone encounters for fever, were recorded. Fever was detected in 80 (5%) of a total of 1610 direct encounters: 36% of those below 7 years of age (n = 70) were febrile. One-third of the total encounters for fever were telephone encounters (n = 36), of which 30% were managed by the receptionists. A wide range of diagnoses were made, most of which were associated with infectious diseases. The distribution of the diagnoses of primary care patients with fever is different from those admitted to hospital for fever of unknown origin. General practitioners and their receptionists should consider fever a diagnostic challenge, especially when the patient is handled over the telephone. PMID- 1459380 TI - Pregnant women's ailments and psychosocial conditions. AB - Pregnant women's ailments may cause anxiety and reduce the quality of life. Sixty five pregnant women were followed prospectively in antenatal care in general practice, and spontaneously reported ailments not associated with serious pregnancy complications were registered prospectively. The vast majority of pregnant women spontaneously reported one or more ailments. A higher number of ailments was reported by women with psychosocial problems and heavy physical work. Abdominal pain was more often reported by women assessed as having psychosocial problems. Based on background knowledge, clinical observations and a somewhat extended history on the psychosocial situation, it is possible to identify a subgroup of women who experience a more than 50% increase in the frequency of such ailments. Reporting of a high number of ailments in antenatal care may provide the clinician with important clues regarding need for psychosocial support. PMID- 1459381 TI - Striking balances: detachment or empathy in the management of Parkinson's disease? AB - This paper, based on in-depth interviews with a group of 18 GPs, was part of a wider study of what GPs and patients thought about communication between them in the case of Parkinson's disease. Four areas where GPs experienced anxiety and uncertainty in responding to their Parkinson's disease patients were examined: that of sustaining care over time; accepting that patients cannot be cured; managing the task of 'just being there' with patients; and responding to patients with communication impairments. Such uncertainties have to be managed if doctors are to accomplish their work lives. The paper goes on to examine how GPs struck balances for themselves between detachment and empathy to keep uncertainty at bay, enabling some GPs to be responsive to patients' needs and others less so. An understanding of these difficulties and strategies has important implications for doctor-patient communication. Some suggestions for change are discussed. PMID- 1459382 TI - Cataract, functioning and co-morbidity: a cross-sectional study in family practice. AB - Cataract is a slowly developing eye disease, the prevalence of which rises with age. Although patients often adapt to the diminished visual acuity accompanying the development of cataracts, their functional health may be impaired by poor vision. An index for visual functioning was derived from the literature. As older people often have additional chronic diseases, vision, visual functioning index and chronic co-morbidity were measured. Functional health was measured with different validated instruments. Eighty cataract patients participated in this study and were visited at home. Results showed statistically significant correlations between vision and co-morbidity on the one hand and visual functioning and functional health on the other. As in most participants vision was only slightly impaired, these results might even be more pronounced in patients with mature cataract. We conclude that indications for cataract surgery might not only be derived from visual acuity, but also from visual functioning and functional health. PMID- 1459383 TI - The effects of treatment of urinary incontinence in general practice. AB - A total of 110 women who had reported urinary incontinence to their general practitioners were randomly assigned to a treatment or control group. Treatment consisted of pelvic floor exercises in the case of stress incontinence and bladder training in the case of urge incontinence. The results were measured after 3 and 12 months by a research assistant on the basis of a constructed severity scale, an incontinence diary, and a comparison by the patients themselves of their previous and current conditions. After 3 months the control group were given the same treatment. After a further 3 and 12 months, they were assessed in exactly the same way as the treatment group. After 3 months about 60% of the patients were either dry or only mildly incontinent; the mean number of wet episodes had gone down from 20 to 7, and 74% of the women felt improved or cured. These results were later corroborated by the control group. After 12 months this successful outcome was improved slightly further. It may be concluded that the majority of women with incontinence can be successfully treated by the general practitioner. The effect of this treatment continues after one year. PMID- 1459384 TI - Morbidity from childhood to adulthood. The medical life history of 103 patients. AB - The aim of the study was to investigate the relationship between presented morbidity in consecutive periods of time in the first 35 years of life. Data were collected in a large rural general practice from 1946 to 1990 and covered 103 persons born between 1946 and 1959 in a general practice in the east of The Netherlands. Morbidity scores were calculated for all registered diagnoses in 5 year periods. Morbidity was allocated to three degrees of seriousness, to all atopic disorders, and to eight important diagnosis groups. There were strong correlations between consecutive time periods for all but serious morbidity. The same pattern was found between 0-4 years of age and consecutive periods till the age of 20-25. After this age no significant correlations could be established. Atopic disorders were inter-related in the first 20 years of life. Strong correlations were also found for eczema and lower respiratory tract infections in the first 20 years, while strong correlations were found for accidents and nervous complaints between the ages of 20 and 35. We conclude that causes of morbidity presented in general practice in childhood and adulthood are strongly inter-related over consecutive 5-year periods. PMID- 1459385 TI - Eliciting patients' views of the cause of their problem: a practical strategy for GPs. AB - One thousand consecutive consultations with one general practitioner were studied to determine the value of seeking the patients' ideas about the cause of their condition. The diagnosis was an issue in 543 of the consultations. A total of 150 patients spontaneously volunteered a clear cause. When the remainder were asked to express their ideas about cause, 266 were able to do so. There were no significant age or sex differences between those who were able to express a cause compared with those who were unable to. The most common ideas expressed were infection, injury, anxiety and allergy. Thirty per cent of ideas were valuable to the doctor in reaching a deeper understanding of the patient's concerns over the condition and 20% helped determine the most likely cause of the condition. There were no significant differences in the value to the doctor between the causes spontaneously volunteered and those given as a result of questioning. The most valuable ideas to the doctor were cancer, anxiety, age, occupation, and heart disease. This study suggests that in the half of general practitioner consultations in which diagnosis is an issue, it is worthwhile seeking the patients' ideas as to cause of their condition. PMID- 1459386 TI - Women's undefined disorders--a challenge for clinical communication. AB - Patients presenting illness without disease are common in general practice. A clinical communicative method was developed in order to clarify women's 'undefined' disorders. Outcomes from this approach registered from 122 audiotaped consultations were qualitatively analysed, in order to explore potential conditions and premises constituting the phenomena labelled as undefined. Knowledge produced by female patients was applied for transformation of the undefined nature of the problem into various levels of medical understanding. Gender-specific illness-promotive mechanisms were identified, as well as certain communicative dilemmas distorting symptom presentation into undefinedness. Relevant medical management was also suggested. PMID- 1459387 TI - Patient satisfaction in primary health care. A comparative study of two modes of treatment for hypertension. AB - The object of this study was to compare patients' experiences of two different treatments of hypertension (one mainly non-pharmacological and one pharmacological) and study the degree of patient satisfaction and experiences of treatment in general. The 165 patients in the non-pharmacological group participated in a two-year-long study of non-pharmacological treatment of hypertension (NPTH) at eight health centres in mid-Sweden. In addition to regular visits to the same doctor at the health centre, patients received monthly check ups by a nurse at the health centre and participated in information programmes and group activities. The NPTH patients also used cuffs for home measurements of blood pressure. The 85 patients in the control group were recruited from two health centres and received traditional, pharmacological treatments of hypertension. The hypothesis was that the patients in the NPTH group would experience satisfaction with the treatment and perceive the treatment in general as more positive than those in the control group. The 250 patients have answered a postal inquiry with structured and open questions concerning the treatment. The results show that the patients in the NPTH group throughout this study have experienced higher satisfaction with the treatment and had a more positive attitude towards the treatment than the controls. The content and design of the treatment obviously had a positive influence on patient satisfaction. PMID- 1459388 TI - Patient-centredness: is it applicable outside the West? Its measurement and effect on outcomes. AB - Patient-centredness has been shown to be associated with improved patient outcomes in the West. The objectives of this study were: (i) to further test a specific method for measuring patient-centredness that had previously demonstrated validity and reliability, and (ii) to test the effectiveness of a patient-centred approach amongst poor, non-Western people in South Africa. Patient-centredness was measured in terms of the practitioner's facilitation of the patient's reasons for coming, including symptoms, thoughts, feelings, and expectations. The study involved nurse practitioners and medical doctors in three primary care settings with patients from eight language groups. The method for measuring patient-centredness was found to be valid, reliable (inter-rater correlations, rs = 0.95, 0.88, and 0.87), sensitive, and practical, being inexpensive, time efficient, suitable for consultations involving interpreters, and not requiring transcripts. The score for the first 2 minutes of the consultation correlated highly with the score for the entire consultation (rs = 0.92), which could make the method useful on a large scale. Patient-centredness itself, was also time effective, applicable to cross-cultural consultations involving interpreters, and was associated with patients feeling understood (P = 0.03), patient-practitioner agreement (P = 0.049), symptom resolution (P = 0.01), and concern resolution (P = 0.006). This study supports the effectiveness of patient-centred interviewing in a non-Western setting as well as this method of assessing it. PMID- 1459389 TI - Differences between patient and physician perceptions of predicted compliance. AB - One approach to improving patient compliance is for physicians to adapt their behaviour to fit patients' psychological characteristics. Previous university based research has suggested that physician adaptation to patients' locus of control interferes with patient-physician congruence on expected compliance, but not with congruence on satisfaction with their relationship. This study was conducted in a community practice to clarify the relationship between the physician's adaptation to locus of control and likelihood of and commitment to compliance, and satisfaction with the doctor-patient match. One physician saw 148 patients with a variety of illnesses after they had completed the Health Locus of Control (HLC) questionnaire. The physician altered how he spoke with a patient based on whether the patient scored internally or externally on the HLC. After the encounter, both patient and physician rated the patient's likelihood of and commitment to complying with each of the three recommendations. The physician and each patient also rated their satisfaction with the match between them. Patients' ratings of commitment, likelihood, and satisfaction were significantly higher than those of the physician. Unlike earlier results, there were strong correlations between the patients' and physician's estimates of compliance (commitment and likelihood). Just as with the previous study, there was no correlation between the levels of physician and patient satisfaction with their match. This study indicates that physician adaptation to patients' locus of control does not interfere with compliance outcomes of doctor-patient encounters. Whether such adaptation will improve compliance outcomes is yet to be determined. PMID- 1459390 TI - Medical students' perceptions of an undergraduate general practice preceptorship. AB - A survey was undertaken to evaluate an undergraduate general practice preceptorship by means of an open-ended six-item questionnaire given to students at the end of their general practice attachment. The aim of the survey was to evaluate the preceptorship as a learning experience and to examine ways in which the preceptorship might be improved. Questionnaires from two medical student years (1985 and 1990) were examined retrospectively. Of 398 potential responders, 386 (97%) had completed questionnaires. Students expressed a very high level of satisfaction with the attachment and this was expressed most often in terms of the personal interest shown by the general practitioner, the variety of clinical problems encountered, and the experience gained in managing common clinical problems. Areas of the attachment which students felt could be improved were: involvement in the consultation, the time constraints on teaching and the teaching of practical skills. The paper discusses possible improvements which could be made to preceptorship programmes on the basis of these findings. PMID- 1459391 TI - International primary care classifications: the effect of fifteen years of evolution. AB - To better understand the development of primary care classifications over the past 15 years, 10 primary care databases have been retrospectively analysed using the structure of the International Classification of Primary Care (ICPC) as the basis. All datasets were based on routine data collection using different classification systems by several family physicians during all encounters with their patients over considerable periods of time, in most cases one year. The prevalences or the rates of the available diagnostic--and reason for encounter- classes were distributed over four frequencies. With a few exceptions the distribution of diagnostic labels referring to common diseases is surprisingly similar. The use of ICPC however results in a quantum leap in the use of symptom and complaint diagnoses. Because of this shift primary care physicians now have available a classification with 400 diagnostic classes used with a prevalence of > or = 1/1000 patient-years or per 1000 visiting patients per year. The classification of reasons for encounter allows the physician to identify over 300 reasons for encounter used > or = 1/1000 patient years or per 1000 visiting patients per year. Family physicians have been successful in the development of new primary care classifications. Rag bag rubrics which are the result of the structure of ICPC are used relatively often and deserve more attention from primary care taxonomers. PMID- 1459392 TI - The conversion between ICPC and ICD-10. Requirements for a family of classification systems in the next decade. AB - The International Classification of Primary Care (ICPC) was developed to order medical concepts into classes that have been chosen for their relevance for family medicine. Family physicians use this to label the most prevalent conditions in their practice as well as their patients' symptoms and complaints. At the same time they do not want to be divorced from the needs of the medical community at large as these are reflected in the most recent medical nomenclature: the Tenth Revision of the International Classification of Diseases (ICD-10). A full conversion between all classes in the first and seventh component of ICPC (n = 646) with those of ICD-10 (n = 1983), with the exception of the chapter on external causes, has been prepared. It was concluded that ICD 10 at the three-digit level cannot function as a core classification for an international primary care system. Of the three-digit ICD-10 rubrics only 120 are compatible on a one to one basis with an ICPC rubric. A total of 114 three-digit ICD-10 rubrics have to be broken open into four-digit rubrics to allow at least one compatible conversion to one or more ICPC rubrics. On this basis only 25% of the diagnostic classes in ICPC can be converted to a single three- or four-digit ICD-10 rubric without lumping. The rest of ICD-10, either on the three- or on the four-digit level, has to be grouped into combinations of classes (lumping) to allow compatible conversion to the remaining rubrics of ICPC. Even though ICD-10 cannot serve as a core classification for primary care, a technical conversion between ICPC and ICD-10 is practically always possible which allows primary care physicians to implement ICD-10 as a contemporary nomenclature within the classification structure of ICPC. PMID- 1459393 TI - Minimum basic data set in general practice: definitions and coding. AB - A minimum basic data set (MBDS) was designed and used in general practice. The most important purpose and need for establishing such a data set is to assist in the provision of patient care. MBDS is designed to meet common needs for many general practitioners. Minimum means that individual programmes or the GP are free to collect as much additional data as they may wish. The MBDS includes two kinds of data: permanent and dynamic/encounter items. Permanent items are: patient data (identification, problem list, chronic treatments, source of payment) and GP data (professional characteristics). Dynamic/encounter items are: date, place, reasons for encounter, problems, process and prior encounter status. PMID- 1459394 TI - Computerization of general practices and quality control. Blood glucose regulation in type 2 diabetics investigated in the Registration Network family practices. AB - The extent to which computerized medical administration facilitates quality control was studied using as an example the quality of blood glucose regulation in diabetics supervised by general practitioners in 11 computerized practices. Systematic use of the general practice computer rapidly provided an unequivocal answer that 37% of such patients were not regulated in accordance with the guidelines for type 2 diabetes mellitus of the Dutch College of General Practitioners. The extra workload for the participating general practitioners was minimal. Automated recording of problem lists, as applied in the general practices belonging to the Registration Network, facilitates access to data on chronic diseases and risk factors for purposes of research, quality control and quality assessment. PMID- 1459395 TI - General practitioners' attitudes towards future developments in practice computing--a representative survey in the north of Germany. AB - A postal questionnaire was sent to a random sample of general practitioners in Lower Saxony, Germany to assess how general practitioners regard newly developed but not yet implemented options of practice computers and future applications such as expert systems and information retrieval systems. Replies were received from 276 (response rate 73.6%) general practitioners. Replying doctors were younger (P < 0.05) but they did not differ by sex, practice location, type of vocational training and grade of computerization from non-responding GPs. Twenty eight per cent of the practices were computerized. Doctors who currently used a computer and those who intended to do so within the next 5 years were significantly younger than those doctors who did not intend to computerize their practice (P < 0.001). Female doctors were less willing to buy a computer than their male colleagues (P < 0.05). A computerized drug database and a medical library ranked best from 8 options given. Overall attitudes to all features were positive, except for an expert system giving criteria for referrals to specialist care. Doctors already working with a computer and those intending to buy one were significantly more positive about future options for computers than those doctors who do not intend to use a computer (P < 0.01). GPs' attitudes about new features of practice computers in general were positive but even more so about those options which are already available. Referral to a specialist seems to be a crucial point for GPs--they apparently do not want to be guided by a computer here.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459396 TI - Selections from current literature: treatment of congestive heart failure with angiotensin converting enzyme inhibitors. PMID- 1459397 TI - Cloning and expression in Escherichia coli of a phoA gene encoding a phosphate irrepressible alkaline phosphatase of Zymomonas mobilis. AB - The Zymomonas mobilis phoA gene, encoding a phosphate-irrepressible alkaline phosphatase (ZAPase), was cloned and its expression was studied in phoA mutants of Escherichia coli. The ZAPase was recovered in the soluble fraction of E. coli. The enzyme was synthesized constitutively and its synthesis not repressed by phosphate, unlike the phoA gene of E. coli. The phoA gene of Z. mobilis was mutagenized by Mini Mu PR13 and the mutated gene crossed into Z. mobilis in order to obtain phoA mutants by reverse genetics. Although Z. mobilis mutants with Mini Mu PR13 integrated in the chromosome were obtained, none had an allele replacement for none was defective in ZAPase. PMID- 1459398 TI - Biosynthesis of modified peptidoglycan precursors by vancomycin-resistant Enterococcus faecium. AB - In the presence of bacitracin, vancomycin-resistant Enterococcus faecium (vanA phenotype) accumulate UDP-N-acetylmuramyl(UDP-Mur-NAc)-tetrapeptide and a UDP MurNAc-depsipentapeptide containing lactate substituted for the carboxy-terminal D-alanine residue. In an in vitro peptidoglycan polymerization assay, the modified precursors function and confer resistance to vancomycin. PMID- 1459399 TI - Urea-hydrolysis-dependent citrulline synthesis by Ureaplasma urealyticum. AB - Some of the ammonia produced by hydrolysis of urea by Ureaplasma urealyticum is channelled into an anabolic pathway with resultant 'de novo' synthesis of citrulline. The organism appears to possess ornithine carbamoyltransferase and carbamoyl phosphate synthetase or some modified form of these enzymes. PMID- 1459400 TI - Ergosterol levels in two L-methionine-enriched mutants of the methylotrophic yeast Candida boidinii ICCF26. AB - Two L-methionine-enriched mutants, SN-78 and SE-57, were isolated in a sulphur deficient medium from the methylotrophic yeast Candida boidinii ICCF26. No significant differences were detected between the L-cysteine pools of the mutants and the wild-type. In mutant strain SE-57, S-adenosylmethionine and ergosterol levels were higher than in the wild-type strain, while in the other mutant, SN 78, the levels were lower. The evidence presented would suggest that, in both the mutants and the wild-type used in this study, S-adenosylmethionine was of key importance for the accumulation of L-methionine and ergosterol. PMID- 1459401 TI - Detection and differentiation of Colletotrichum gloeosporioides isolates using PCR. AB - An oligonucleotide primer (CgInt), synthesised from the variable internally transcribed spacer (ITS) 1 region of ribosomal DNA (rDNA) of Collectotrichum gloeosporioides was used for PCR with primer ITS4 (from a conserved sequence of the rDNA) to amplify a 450-bp fragment from the 25 C. gloeosporioides isolates tested. This specific fragment was amplified from as little as 10 fg of fungal DNA. A similar sized fragment was amplified from DNA extracted from C. gloeosporioides-infected tomato tissue. RAPD analysis divided 39 C. gloeosporioides isolates into more than 12 groups linked to host source and geographic origin. Based on the results obtained, the potential of PCR for detection and differentiation of C. gloeosporioides is discussed. PMID- 1459402 TI - An FNR-dependent promoter from Escherichia coli is active and anaerobically inducible in Paracoccus denitrificans. AB - A transcriptional fusion of a synthetic FNR-dependent promoter derived from Escherichia coli has been introduced into Paracoccus denitrificans on a broad host-range plasmid. The patterns of expression of beta-galactosidase from this fusion and from a control which is not regulated by FNR have been studied. The results indicate that P. denitrificans expresses a transcriptional regulator which has a very similar DNA-binding specificity to FNR, and responds to a similar physiological signal. PMID- 1459403 TI - Pulsed field gel electrophoresis of representatives of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains. AB - Using field inversion gel electrophoresis (FIGE), different Mycobacterium tuberculosis strains, such as phage prototypes, exhibit different DNA restriction patterns which are easy to compare. Virulent and avirulent variants of M. tuberculosis H37, as well as daughter strains of M. bovis BCG, display characteristic DNA profiles. BCG strains isolated from suppurative adenitis following vaccination of French patients showed patterns identical to the BCG Pasteur strain used for vaccination. These results demonstrate that FIGE of DNA restriction fragments generated by DraI represents a suitable technique for the analysis of mycobacteria at a genomic level. The DraI profiles allow the differentiation and precise identification of the BCG Pasteur, Glaxo, Russian and Japanese strains. PMID- 1459404 TI - Analysis of genomic DNA from Chlamydia trachomatis for Dam and Dcm methylation. AB - Chlamydia trachomatis is a Gram-negative eubacterium with a dimorphic developmental cycle and obligate intracellular growth in the eucaryotic host. The Dam transmethylase of Escherichia coli methylates at the N6 position of adenine in the sequence 5'-GATC-3' and the Dcm transmethylase adds methyl groups to the C5 position of the internal cytosines in the sequences 5'-CCWGG-3'. In contrast to E. coli, C. trachomatis DNA appears to have unmethylated Dam sites and only low level Dcm methylation. PMID- 1459405 TI - Mineralization of 2-chloro- and 2,5-dichlorobiphenyl by Pseudomonas sp. strain UCR2. AB - Pseudomonas sp. strain UCR2 was isolated from a multi-chemostat mating experiment between a chlorobenzoate-degrader, Pseudomonas aeruginosa strain JB2, and a chlorobiphenyl-degrader, Arthrobacter sp. strain B1Barc. Strain UCR2 differed from either of the parental organisms in that it grew on both 2-chloro- and 2,5 dichlorobiphenyl with concomitant release of chloride. Phenotypic typing by the Biolog system indicated that strain UCR2 shared greater similarity with strain JB2 (88%) than strain B1Barc (3%). In DNA:DNA hybridization experiments, genomic DNA from strain UCR2 hybridized with both strain JB2 and strain B1Barc, with the former pairing yielding a much stronger signal than the latter. In contrast, no hybridization whatsoever was observed when the parental organisms strains JB2 and B1Barc were probed against each other. PMID- 1459406 TI - Temperature-sensitive mutants of the Mycobacterium plasmid pAL5000. AB - Two plasmids were isolated as thermosensitive replicons following in vitro mutagenesis of pB4, a pAL5000 derivative mycobacteria/Escherichia coli shuttle plasmid. Plasmids pCG59 and pCG63 replicate at 30 degrees C but not at 39 degrees C. This will allow their utilisation for transposon delivery, site-specific integration, or allele exchange. PMID- 1459407 TI - Dimorphism in Itersonilia perplexans: yeast and hyphal phases differ in their sensitivity to mycocins produced by tremellaceous yeasts. AB - The monokaryotic yeast phase of the heterobasidiomycete Itersonilia perplexans, unlike the hyphal phase, was found to be sensitive to mycocins produced by killer strains of Cryptococcus humicola, Cr. laurentii, Cystofilobasidium bisporidii and Rhodotorula fujisanense. Both the yeast and hyphal phases wer resistant to mycocins of Cr. podzolicus, Filobasidium capsuligenum, Rhodotorula glutinis, Rh. mucilaginosa, Rh. pallida, Sporidiobolus johnsonii, Sb. pararoseus and Sporobolomyces alborubescens. The different sensitivity patterns of yeast and hyphal phases are probably caused by biochemical differences in the cell walls. PMID- 1459408 TI - Enterotoxicity and immunological properties of two mutant forms of Escherichia coli STIp with lysine or arginine substituted for the asparagine residue at position 11. AB - Two variants of Escherichia coli heat-stable enterotoxin Ip, in which the amino acid residue at position 11 was substituted with lysine or arginine, were purified to near homogeneity from the culture supernatants of toxin-producing mutant strains. Neither the purified heat-stable enterotoxin Ip(Lys-11) nor the purified heat-stable enterotoxin Ip(Arg-11) showed a positive response in the suckling mouse assay or in the mouse intestinal loop assay. Furthermore, live bacteria producing these mutant heat-stable Ip enterotoxins did not cause fluid accumulation in mouse intestinal loops, in contrast to bacteria producing native heat-stable enterotoxin Ip. Nevertheless, antisera raised against both heat stable enterotoxin Ip(Lys-11) and heat-stable enterotoxin Ip(Arg-11) neutralized the enterotoxic activity of native heat-stable enterotoxin Ip. These results demonstrate that heat-stable enterotoxin Ip(Lys-11) and heat-stable enterotoxin Ip(Arg-11) lose enterotoxicity but retain epitopes which are common to native heat-stable enterotoxin Ip. PMID- 1459409 TI - Characterization of two forms of hemagglutinin/protease produced by Vibrio cholerae non-O1. AB - Two forms (34 kDa and 32 kDa) of hemagglutinin/protease produced by Vibrio cholerae non-O1 were characterized. The hemagglutinin/protease purified by immunoaffinity column chromatography using a monoclonal antibody was essentially a 34-kDa form. By incubation of the purified 34-kDa form at 37 degrees C, it was processed (autodigested) to the 32-kDa form. The N-terminal 20 amino acid sequences of both the 34- and 32-kDa forms were identical, suggesting that proteolytic processing at the C-terminal region of the 34-kDa hemagglutinin/protease resulted in the 32-kDa form. With this shift, protease activity increased, but hemagglutinating activity decreased, suggesting that the C-terminal region of the hemagglutinin/protease is related to hemagglutinating activity. PMID- 1459410 TI - Mycobacterium avium rough-to-smooth colony conversion resulting from growth in Tween 80 without presence of type-specific glycopeptidolipid antigens. AB - Growth of a Mycobacterium avium complex serotype 20 rough-colony variant in 1.0% Tween 80 resulted in a smooth-colony morphological conversion that was reversible upon removal of Tween and was not associated with the presence of serotype specific glycopeptidolipid antigens. Electron microscopic examination suggested the role of an outer layer in the Tween-related morphological modification. PMID- 1459411 TI - Antibody-mediated uncoating of adenovirus in vitro. AB - In a virus destabilization assay in vitro it was demonstrated that exposure of adenovirus to proteins will non-specifically protect the virus from being uncoated following transfer to low pH and hypotonic conditions. Such uncoating was also fully inhibited upon pretreatment of virus with 0.05% of the non-ionic detergent polyoxyethylenesorbitan monolaurate (Tween 20). However, in the presence of low concentrations of Tween 20 it was shown that monospecific immunoglobulins, directed against the fiber antigen and polyspecific antibodies produced in response to intact virions, were able to overcome the detergent protecting effect of uncoating. Immunoglobulins directed towards the remaining outer-capsid components, the hexon, the penton base and the protein IIIa, revealed no such effects. The antifiber-mediated uncoating was paralleled by an aggregation of the virions. The data suggest that the virion-stabilizing effect of salt is enhanced by the hydrophobic action of a non-ionic detergent. Under these conditions the interaction between antifiber antibodies and fibers of the virion will trigger a destabilization of the virion upon transfer to low pH and hypotonic conditions. PMID- 1459412 TI - N-acetyl-D-glucosamine-specific lectin purified from Vibrio cholerae 01. AB - An N-acetyl-D-glucosamine-specific cell associated hemagglutinin (HA) was isolated and purified from a strain of Vibrio cholerae 01 by chitin affinity chromatography followed by separation on Bio Gel P-150. A single stained protein band of 47 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE) was observed with the purified HA. HA-antisera produced a single precipitin band against the purified HA in an immunodiffusion test without exhibiting any reactivity towards purified lipopolysaccharide (LPS). Purified HA, used as solid phase antigen in an enzyme-linked immunosorbent assay (ELISA), reacted strongly with HA-antisera but cross-reacted negligibly with antisera raised against purified LPS. Hemagglutinating activity of the purified HA was highly sensitive to N-acetyl-D-glucosamine. The immunogold-labelling method using HA-antisera confirmed the location of the HA on the surface of the bacterial cells. The HA antisera reacted with a protein component of the homologous outer membrane preparation. A significant inhibition was observed in the adhesive capability of the V. cholerae 01 strain to isolated rabbit intestinal epithelial cells (RIEC) in vitro when the later were pre-treated with the purified HA. PMID- 1459413 TI - Interrelations between populations of methanogenic archaea and sulfate-reducing bacteria in the human colon. AB - In humans, CH4 is produced in the colon by methanogenic archaea and is detected in breath samples from approximately 50% of healthy adults, identified as CH4 excretors. Methanogenesis and sulfate reduction have been described as two mutually exclusive processes, potentially regulated by sulfate availability. To determine whether microbial population balances reflected these apparently co regulated activities, we compared sulfate-reducing bacteria, methanogenic archaea, sulfate and sulfide concentrations in faeces of 10 CH4-excretors (CH4+) and 9 non-CH4-excretors (CH4-). The mean +/- SE of the logarithm of methanogenic archaea per gram wet weight were 9.0 +/- 0.2 and 4.0 +/- 0.7 for CH4+ and CH4-, respectively (P < 0.001). Sulfate-reducing bacterial counts were 6.5 +/- 0.1 and 7.3 +/- 0.2, respectively (P < 0.001). Fecal sulfate and sulfide concentrations did not differ between groups. These results suggest that a competitive interrelation between methanogenic archaea and sulfate-reducing bacteria occurs in the human colon. However, it does not lead to a complete exclusion of the two populations. PMID- 1459414 TI - Purification and partial characterization of two azoreductases from Shigella dysenteriae type 1. AB - Two azoreductases (I and II) were purified to homogeneity from extracts of Shigella dysenteriae (type 1). Azoreductase I was a dimer of identical subunits of M(r) 28,000, whereas azoreductase II was a monomer of 11,000 M(r). Both were flavoproteins, each containing 1 mol of FMN per mol enzyme. Both NADH and NADPH functioned as electron donors for the azoreductases. Azoreductase I used Ponceau SX, Tartrazine, Amaranth and Orange II as substrates. Azoreductase II utilized all the dyes except Amaranth. PMID- 1459415 TI - Binding of bovine lactoferrin to Streptococcus agalactiae. AB - Bovine lactoferrin is an iron-binding protein present in mammary gland secretions. The exposure of Streptococcus agalactiae to bovine lactoferrin resulted in the binding of this protein to all the 12 strains of bovine origin tested, and also, although to a lesser degree, to the five tested strains of human origin. The interaction of lactoferrin with one high-binding bovine strain (24/60, the prototype NT/X strain) was studied. Binding was time-dependent, dose dependent, and saturable. The binding of lactoferrin was slightly affected by cultivation conditions, and appeared to be heat-stable. The binding of biotinylated lactoferrin was inhibited by unlabelled lactoferrin but not by bovine serum albumin. PMID- 1459416 TI - Siderophores and related outer membrane proteins produced by pseudomonads isolated from eels and freshwater. AB - A total of 46 environmental pseudomonads, together with six type strains, were examined for their siderophore-producing activity. All strains were able to grow under iron-limiting conditions, gave orange halos in the CAS agar assay, and produced hydroxamates, and some of them also produced phenolate-type compounds. Bioassays showed that all strains, except Pseudomonas aeruginosa, promoted growth of mutant strain Arthrobacter flavescens JG-9, deficient in hydroxamate production, and some of them promoted growth of Salmonella typhimurium enb-1, which requires enterobactin for growth. The presence of iron-regulated outer membrane proteins was observed, the molecular size of the main induced proteins ranged between 76 and 93 kDa. PMID- 1459417 TI - Stimulation of neutrophil leukocyte chemotaxis by a cloned cytolytic enterotoxin of Aeromonas hydrophila. AB - A cytolytic enterotoxin produced by Aeromonas hydrophila, isolate SSU, has been cloned in our laboratory. This enterotoxin lysed rabbit red blood cells, destroyed Chinese hamster ovary cells, caused fluid secretion in rat ligated ileal loops, inhibited the phagocytic function of mouse phagocytes, and was lethal to mice when injected intravenously. In this study, the effect of this cytolytic enterotoxin on the chemotaxis of human leukocytes (cell line RPMI 1788) was examined. This toxin, at concentrations from 92.5 to 370 ng/ml, significantly stimulated the chemotactic activity of human leukocytes in a dose-dependent fashion. The stimulation of leukocyte chemotaxis elicited by cytolytic enterotoxin was abolished when the toxin was neutralized, heated, or exposed to low pH values. This stimulatory effect also was inhibited by various concentrations of pertussis toxin. These results demonstrated that cytolytic enterotoxin may stimulate increased chemotaxis of human leukocytes, and suggest that human leukocytes may possess cytolytic enterotoxin receptors which may be coupled to pertussis toxin-sensitive G-protein. PMID- 1459418 TI - Phosphate starvation affects the synthesis of outer membrane proteins in Thiobacillus ferrooxidans. AB - The outer membrane protein (omp40) component from the chemolithoautotrophic acidophilic Thiobacillus ferrooxidans is apparently regulated by the external pH and the concentration of phosphorus. Its amino-terminal sequence showed little identity with the Escherichia coli OmpC, OmpF or PhoE porins, but was 38.5% identical to the outer membrane channel-forming protein NosA from Pseudomonas stutzeri, whose expression is also regulated environmentally. In addition, the partial amino acid sequence of T. ferrooxidans omp40 showed between 34 and 38% identity with the amino-terminal end of the small outer membrane proteins Rck and PagC from Salmonella typhimurium and OmpX from Enterobacter cloacae. PMID- 1459419 TI - Influence of nutrient media on the chemical composition of the exopolysaccharide from mucoid and non-mucoid Pseudomonas aeruginosa. AB - Two mucoid Pseudomonas aeruginosa strains and their non-mucoid revertants isolated from two different clinical origins (cystic fibrosis and bronchiectasis) were grown in various chemically defined media. The extracted exopolysaccharide was characterized by gas-liquid chromatography and 1H-NMR spectroscopy. The exopolysaccharide was always heterogeneous, with an alginate fraction and a neutral fraction essentially composed of glucose, galactose, rhamnose and hexosamines. The alginate composition (mannuronate/guluronate ratio and O acetylation degree) changed according to the carbon source in nutrient media and whether the strains tested were responding differently to these environmental stimuli. In all cases, the best carbon source for the alginate production was glycerol: the two cystic fibrosis strains produced a predominantly O-acetylated alginate whereas only the mucoid bronchiectasis strain produced a polymannuronate exopolysaccharide. PMID- 1459420 TI - The bacteriocidal effects of transition metal complexes containing the NO+ group on the food-spoilage bacterium Clostridium sporogenes. AB - The chemical and molecular mechanism of toxicity of nitrite towards food-spoilage bacteria such as Clostridium botulinum or Clostridium sporogenes is not well understood. In order to discover the active species and explore its chemistry, a number of compounds related to nitrite were synthesized. Their bacteriocidal effects on C. sporogenes were investigated in Oxoid nutrient broth No. 2 growth medium at pH 7.0. Inhibition of cell growth, expressed as the concentration which causes 50% cell inhibition, was observed with nitrite at 10 mM, whereas [Fe4S3(NO)7]-(the anion of Roussin's black salt) and (Fe2(SCH2CH2OH)2(NO)4] (a water-soluble Roussin's red salt ester) were found to be effective at 0.001 mM and 0.005 mM, respectively, confirming previous reports that iron-sulphur nitrosyl complexes are much more toxic to these organisms than nitrite itself. The nitroprusside anion, [Fe(CN)5NO]2- was found to be toxic at 0.030 mM and the corresponding chromium species, [Cr(CN)5NO]3-, at 0.1 mM. Therefore, on the basis of the number of NO groups present, the nitrosylcyano complexes are comparable in activity with the iron-sulphur-nitrosyl compounds. These results show that neither iron nor sulphur are essential for the bacteriostatic effect of the Roussin's type compounds. The property that all these compounds have in common is that they contain NO+. It is proposed that this is the active species responsible for the preservative effect of nitrite, and that a relationship may exist between the N-O stretching frequency, a measure of the NO+ character, and the toxicity of these NO(+)-containing complexes. PMID- 1459421 TI - Lectin-like activity of Lactobacillus acidophilus strain JCM 1026. AB - The lectin-like activity of the Lactobacillus acidophilus strain JCM 1026 was studied by hemagglutination and hemagglutination-inhibition assays. L. acidophilus strain JCM 1026 was found to hemagglutinate human and animal erythrocytes. Neuraminidase-treatment of human-type O erythrocytes enhanced the activity. Treatment of the bacterial cells with proteinase K reduced hemagglutinating activity significantly. Although several mono- and disaccharides did not inhibit hemagglutination, several different glycoproteins did. These data indicate that a proteinaceous lectin-like component(s) recognizing carbohydrate containing molecules is located on the cell surface of L. acidophilus. PMID- 1459422 TI - Structure of mycoside F, a family of trehalose-containing glycolipids of Mycobacterium fortuitum. AB - Nuclear magnetic resonance spectroscopy, fast-atom bombardment mass spectrometry, gas chromatography-mass spectrometry, as well as chemical degradations were used to elucidate the structure of the major glycolipids of Mycobacterium fortuitum. Three main glycoconjugates were detected and their structures established as 2,3 diacyl, 2,3,4- and 2,3,6-triacyl trehalose. The characteristic infrared spectrum which led to their original designation as mycoside F, a family of glycolipids limited in distribution to M. fortuitum, was due to the nature of the fatty acyl substiuents identified primarily as 2-methyl-octadecen-2-oyl. The antigenic glycolipids typified the biovar. fortuitum, thus allowing its easy recognition from the C-mycoside glycopeptidolipid-containing biovar. peregrinum. PMID- 1459423 TI - Regulation of pag gene expression in Bacillus anthracis: use of a pag-lacZ transcriptional fusion. AB - The production of protective antigen (PA), the common component of the two anthrax toxins, is influenced by the environment. In order to examine factors involved in its regulation, a transcriptional fusion between the promoter region of the PA gene (pag) and the lacZ gene was constructed and introduced into Bacillus anthracis Sterne. Activity of the pag promoter was followed by measuring beta-galactosidase activities under various growth and medium conditions. Expression from the pag promoter was observed throughout exponential-phase and was maximal in early stationary phase. The activity of the pag promoter was stimulated by the addition of glucose in the medium. PMID- 1459424 TI - Uniparental cytogamy: a novel method for bringing micronuclear mutations of Tetrahymena into homozygous macronuclear expression with precocious sexual maturity. AB - A new method of inducing self-fertilization, uniparental cytogamy, yields homozygous germinal and somatic genotypes in the ciliate Tetrahymena thermophila. Progeny are highly fertile and show a marked tendency for precocious sexual maturity. This method is highly effective in protocols designed to generate and express nonlethal dominant or recessive mutations. PMID- 1459425 TI - Copies of a Stellate gene variant are located in the X heterochromatin of Drosophila melanogaster and are probably expressed. AB - Two variants of X chromosome Stellate genes responsible for crystal formation in XO male primary spermatocytes occupy different genome positions. The majority if not all of the 1250-bp Stellate genes are located at the 12E site where the Ste locus has been mapped and almost all of the 1150-bp Stellate repeats are concentrated in the distal X heterochromatin. Sequencing of Stellate genes derived from X heterochromatin reveals the preservation of their open reading frames and precise matching with some Stellate cDNAs reported earlier. At least some heterochromatic Stellate genes are suggested to be expressed and, therefore, involved in the interaction with the Y chromosome locus Su(Ste), as are the Stellate genes from 12E. PMID- 1459426 TI - Sister-chromatid misbehavior in Drosophila ord mutants. AB - In Drosophila males and females mutant for the ord gene, sister chromatids prematurely disjoin in meiosis. We have isolated five new alleles of ord and analyzed them both as homozygotes and in trans to deficiencies for the locus, and we show that ord function is necessary early in meiosis of both sexes. Strong ord alleles result in chromosome nondisjunction in meiosis I that appears to be the consequence of precocious separation of the sister chromatids followed by their random segregation. Cytological analysis in males confirmed that precocious disjunction of the sister chromatids occurs in prometaphase I. This is in contrast to Drosophila mei-S332 mutants, in which precocious sister-chromatid separation also occurs, but not until late in anaphase I. All three of the new female fertile ord alleles reduce recombination, suggesting they affect homolog association as well as sister-chromatid cohesion. In addition to the effect of ord mutations on meiosis, we find that in ord2 mutants chromosome segregation is aberrant in the mitotic divisions that produce the spermatocytes. The strongest ord alleles, ord2 and ord5, appear to cause defects in germline divisions in the female. These alleles are female sterile and produce egg chambers with altered nurse cell number, size, and nuclear morphology. In contrast to the effects of ord mutations on germline mitosis, all of the alleles are fully viable even when in trans to a deficiency, and thus exhibit no essential role in somatic mitosis. The ord gene product may prevent premature sister-chromatid separation by promoting cohesion of the sister chromatids in a structural or regulatory manner. PMID- 1459427 TI - Evidence for intrinsic differences in the formation of chromatin domains in Drosophila melanogaster. AB - The results of an investigation into intrinsic differences in the formation of two different heterochromatic domains are presented. The study utilized two different position effect variegation mutants in Drosophila melanogaster for investigating the process of compacting different stretches of DNA into heterochromatin. Each stretch of DNA encodes for a gene that affects different aspects of bristle morphology. The expression of each gene is prevented when it is compacted into heterochromatin thus the genes serve as effective reporter systems to monitor the spread of heterochromatin. Both variegating mutants are scored in the same cell such that environmental and genetic background differences are unambiguously eliminated. Any differences observed in the repression of the two genes must therefore be the result of intrinsic differences in the heterochromatic compaction process for the two stretches of DNA. Studies of the effects different enhancers of variegation have upon the compaction of the two genes indicate each compaction event occurs independently of the other, and that different components are involved in the two processes. These results are discussed with regard to spreading heterochromatin and the role this process may play in regulating gene expression. PMID- 1459428 TI - Rearrangement of upstream regulatory elements leads to ectopic expression of the Drosophila mulleri Adh-2 gene. AB - The Adh-2 gene of Drosophila mulleri is expressed in the larval fat body and the adult fat body and hindgut, and a 1500-bp element located 2-3 kb upstream of the Adh-2 promoter is necessary for maximal levels of transcription. Previous work demonstrated that deletion of sequences between this upstream element and the Adh 2 promoter results in Adh-2 gene expression in a novel larval tissue, the middle midgut. In this study we show that the upstream element possesses all of the characteristics of a transcriptional enhancer: its activity is independent of orientation, it acts on a heterologous promoter, and it functions at various positions both 5' and 3' to the Adh-2 gene. Full enhancer function can be localized to a 750-bp element, although other regions possess some redundant activity. The ectopic expression pattern is dependent on the proximity of at least two sequence elements. Thus, tissue-specific transcription can involve complex proximity-dependent interactions among combinations of regulatory elements. PMID- 1459429 TI - An examination of the effects of double-strand breaks on extrachromosomal recombination in mammalian cells. AB - We studied the effects of double-strand breaks on intramolecular extrachromosomal homologous recombination in mammalian cells. Pairs of defective herpes thymidine kinase (tk) sequences were introduced into mouse Ltk- cells on a DNA molecule that also contained a neo gene under control of the SV40 early promoter/enhancer. With the majority of the constructs used, gene conversions or double crossovers, but not single crossovers, were recoverable. DNA was linearized with various restriction enzymes prior to transfection. Recombination events producing a functional tk gene were monitored by selecting for tk-positive colonies. For double-strand breaks placed outside of the region of homology, maximal recombination frequencies were measured when a break placed the two tk sequences downstream from the SV40 early promoter/enhancer. We observed no relationship between recombination frequency and either the distance between a break and the tk sequences or the distance between the tk sequences. The quantitative effects of the breaks appeared to depend on the degree of homology between the tk sequences. We also observed that inverted repeats recombined as efficiently as direct repeats. The data indicated that the breaks influenced recombination indirectly, perhaps by affecting the binding of a factor(s) to the SV40 promoter region which in turn stimulated or inhibited recombination of the tk sequences. Taken together, we believe that our results provide strong evidence for the existence of a pathway for extrachromosomal homologous recombination in mammalian cells that is distinct from single-strand annealing. We discuss the possibility that intrachromosomal and extrachromosomal recombination have mechanisms in common. PMID- 1459430 TI - A genetic model for control of hypertriglyceridemia and apolipoprotein B levels in the Johns Hopkins colony of St. Thomas Hospital rabbits. AB - The St. Thomas Hospital (STH) rabbit has been previously shown to have a Mendelian form of hypertriglyceridemia, accompanied by accelerated atherosclerosis, and these animals may serve as a useful model for human dyslipoproteinemia syndromes. Here we describe the establishment of a new colony of these STH animals, and present genetic analysis of triglyceride (TG) and apolipoprotein B (apoB) levels. Segregation analysis of TG in 39 STH animals and 24 controls gave evidence of Mendelian segregation for an allele leading to both elevated TG levels and increased variability in these levels. Predicted means from the most parsimonious model for the Johns Hopkins STH colony were quite similar to that seen in the original London colony, and this model accounted for 80% of the variation in TG seen in the sample. This hypertriglyceridemia locus indirectly influenced the mean apoB levels in these rabbits, and segregation analysis of mean apoB levels suggested a second locus controlling apoB levels. Analysis of residual apoB levels (adjusted for predicted effects of the hypertriglyceridemia locus) revealed clearer evidence for a second locus controlling mean apoB levels in this colony. Arguments for two distinct genetic mechanisms operating in these STH animals are presented. PMID- 1459431 TI - Patterns of interallelic divergence at the rabbit b-locus of the immunoglobulin light chain constant region are in agreement with population genetical evidence for overdominant selection. AB - Population studies at the b-locus of the "constant" regions of the rabbit immunoglobulin kappa 1 light chain (c kappa 1) revealed patterns of gene diversity resembling those that mark the peculiar nature of the major histocompatibility complex, such as large number of alleles, high heterozygosity levels, consistent excess of heterozygous individuals and long allele coalescence times. This paper documents the evolutionary patterns at the b-locus as inferred from DNA sequence comparisons. Among alleles, synonymous substitutions outnumbered expectations for neutral alleles by an order of magnitude. They were distributed randomly throughout the c kappa 1 coding region while interallelic amino acid differences did cluster into segments overlapping with the regions exposed to the solvent. Within these regions, acceptance rates of mutation at amino acid replacement sites were even higher than those at synonymous sites (dr/ds = 1.6-3.0), while in the intervals between these regions the opposite was found (dr/ds approximately 0.3). Under the assumption that allelic variation is adaptive at the molecular surface, the divergence patterns at the b-locus are therefore very similar to those reported for the major histocompatibility complex. An analysis at the quasi silent bas-locus (c kappa 2), which is linked to the b-locus, and comparisons among genes of the "variable" region of the kappa 1 light chains (v kappa 1), revealed patterns of divergence which differed markedly from those observed at the c kappa 1 constant regions. It is suggested that allelic variability at immunoglobulin constant regions can be due to mechanisms similar to those enhancing diversity at histocompatibility loci. PMID- 1459432 TI - Length polymorphisms of simple sequence repeat DNA in soybean. AB - The objective of this work was to ascertain the presence and degree of simple sequence repeat (SSR) DNA length polymorphism in the soybean [Glycine max (L.) Merr.]. A search of GenBank revealed no (CA)n or (GT)n SSRs with n greater than 8 in soybean. In contrast, 5 (AT)n and 1 (ATT)n SSRs with n ranging from 14 to 27 were detected. Polymerase chain reaction (PCR) primers to regions flanking the six SSR loci were used in PCR amplification of DNA from 43 homozygous soybean genotypes. At three loci, amplification produced one PCR product per genotype and revealed 6, 7 and 8 product length variants (alleles) at the three loci, respectively. F1 hybrids between parents carrying different alleles produced two PCR products identical to the two parents. Codominant segregation of alleles among F2 progeny was demonstrated at each locus. A soybean DNA library was screened for the presence of (CA/GT)n SSRs. Sequencing of positive clones revealed that the longest such SSR was (CA)9. Thus, (CA)n SSRs with n of 15 or more are apparently much less common in soybean than in the human genome. In contrast to humans, (CA)n SSRs will probably not provide an abundant source of genetic markers in soybean. However, the apparent abundance of long (AT)n sequences should allow this SSR to serve as a source of highly polymorphic genetic markers in soybean. PMID- 1459433 TI - Population genetics of polymorphism and divergence. AB - Frequencies of mutant sites are modeled as a Poisson random field in two species that share a sufficiently recent common ancestor. The selective effect of the new alleles can be favorable, neutral, or detrimental. The model is applied to the sample configurations of nucleotides in the alcohol dehydrogenase gene (Adh) in Drosophila simulans and Drosophila yakuba. Assuming a synonymous mutation rate of 1.5 x 10(-8) per site per year and 10 generations per year, we obtain estimates for the effective population size (N(e) = 6.5 x 10(6)), the species divergence time (tdiv = 3.74 million years), and an average selection coefficient (sigma = 1.53 x 10(-6) per generation for advantageous or mildly detrimental replacements), although it is conceivable that only two of the amino acid replacements were selected and the rest neutral. The analysis, which includes a sampling theory for the independent infinite sites model with selection, also suggests the estimate that the number of amino acids in the enzyme that are susceptible to favorable mutation is in the range 2-23 at any one time. The approach provides a theoretical basis for the use of a 2 x 2 contingency table to compare fixed differences and polymorphic sites with silent sites and amino acid replacements. PMID- 1459434 TI - The effects of selection on linkage analysis for quantitative traits. AB - The effects of within-sample selection on the outcome of analyses detecting linkage between genetic markers and quantitative traits were studied. It was found that selection by truncation for the trait of interest significantly reduces the differences between marker genotype means thus reducing the power to detect linked quantitative trait loci (QTL). The size of this reduction is a function of proportion selected, the magnitude of the QTL effect, recombination rate between the marker locus and the QTL, and the allele frequency of the QTL. Proportion selected was the most influential of these factors on bias, e.g., for an allele substitution effect of one standard deviation unit, selecting the top 80%, 50% or 20% of the population required 2, 6 or 24 times the number of progeny, respectively, to offset the loss of power caused by this selection. The effect on power was approximately linear with respect to the size of gene effect, almost invariant to recombination rate, and a complex function of QTL allele frequency. It was concluded that experimental samples from animal populations which have been subjected to even minor amounts of selection will be inefficient in yielding information on linkage between markers and loci influencing the quantitative trait under selection. PMID- 1459435 TI - Prediction of selection response for threshold dichotomous traits. AB - This paper presents a formula to predict expected response to one generation of truncation selection for a dichotomous trait under polygenic additive inheritance. The derivation relies on the threshold liability concept and on the normality assumption of the joint distribution of additive genetic values and their predictors used as selection criteria. This formula accounts for asymmetry of response when both the prevalence of the trait and the selection rate differ from 1/2 via a bivariate normal integral term. The relationship with the classical formula R = iota rho sigma G is explained with a Taylor expansion about a zero value of the correlation factor. Properties are illustrated with an example of sire selection based on progeny test performance which shows a departure from usual predictions up to 15-20% at low (0.05) or high (0.95) selection rates. Univariate approximations and extensions to several paths of genetic change are also discussed. PMID- 1459436 TI - Heterozygote advantage and the evolution of a dominant diploid phase. AB - The life cycle of eukaryotic, sexual species is divided into haploid and diploid phases. In multicellular animals and seed plants, the diploid phase is dominant, and the haploid phase is reduced to one, or a very few cells, which are dependent on the diploid form. In other eukaryotic species, however, the haploid phase may dominate or the phases may be equally developed. Even though an alternation between haploid and diploid forms is fundamental to sexual reproduction in eukaryotes, relatively little is known about the evolutionary forces that influence the dominance of haploidy or diploidy. An obvious genetic factor that might result in selection for a dominant diploid phase is heterozygote advantage, since only the diploid phase can be heterozygous. In this paper, I analyze a model designed to determine whether heterozygote advantage could lead to the evolution of a dominant diploid phase. The main result is that heterozygote advantage can lead to an increase in the dominance of the diploid phase, but only if the diploid phase is already sufficiently dominant. Because the diploid phase is unlikely to be increased in organisms that are primarily haploid, I conclude that heterozygote advantage is not a sufficient explanation of the dominance of the diploid phase in higher plants and animals. PMID- 1459437 TI - Using markers in gene introgression breeding programs. AB - We investigate the use of markers to hasten the recovery of the recipient genome during an introgression breeding program. The effects of time and intensity of selection, population size, number and position of selected markers are studied for chromosomes either carrying or not carrying the introgressed gene. We show that marker assisted selection may lead to a gain in time of about two generations, an efficiency below previous theoretical predictions. Markers are most useful when their map position is known. In the early generations, it is shown that increasing the number of markers over three per non-carrier chromosome is not efficient, that the segment surrounding the introgressed gene is better controlled by rather distant markers unless high selection intensity can be applied, and that selection on this segment first can reduce the selection intensity available for selection on non-carrier chromosomes. These results are used to propose an optimal strategy for selection on the whole genome, making the most of available material and conditions (e.g., population size and fertility, genetic map). PMID- 1459438 TI - Maximum likelihood mapping of quantitative trait loci using full-sib families. AB - A maximum likelihood method is presented for the detection of quantitative trait loci (QTL) using flanking markers in full-sib families. This method incorporates a random component for common family effects due to additional QTL or the environment. Simulated data have been used to investigate this method. With a fixed total number of full sibs power of detection decreased substantially with decreasing family size. Increasing the number of alleles at the marker loci (i.e., polymorphism information content) and decreasing the interval size about the QTL increased power. Flanking markers were more powerful than single markers. In testing for a linked QTL the test must be made against a model which allows for between family variation (i.e., including an unlinked QTL or a between family variance component) or the test statistic may be grossly inflated. Mean parameter estimates were close to the simulated values in all situations when fitting the full model (including a linked QTL and common family effect). If the common family component was omitted the QTL effect was overestimated in data in which additional genetic variance was simulated and when compared with an unlinked QTL model there was reduced power. The test statistic curves, reflecting the likelihood of the QTL at each position along the chromosome, have discontinuities at the markers caused by adjacent pairs of markers providing different amounts of information. This must be accounted for when using flanking markers to search for a QTL in an outbred population. PMID- 1459439 TI - RIPping and RAPping at Berkeley. PMID- 1459440 TI - Unicorns revisited. PMID- 1459441 TI - Chi enhances heteroduplex DNA levels during recombination. AB - The major pathway of homologous recombination in Escherichia coli, the RecBCD pathway, is stimulated by Chi sites. To determine whether Chi enhances an early or late step in recombination, we measured formation of heteroduplex DNA (hDNA) in extracts of lambda-infected E. coli. Chi elevated hDNA levels in these extracts, supporting a role for Chi early (before hDNA formation) in recombination. RecA protein and RecBCD enzyme were both necessary for detection of hDNA, indicating that they, too, act early. Analysis of a panel of recBCD mutants indicated that Chi-nicking activity was needed for Chi's stimulation of hDNA formation. These results support a previously proposed model of recombination. Further results suggested that RecBCD enzyme has an additional role late in recombination. PMID- 1459442 TI - Rhizobium meliloti genes involved in sulfate activation: the two copies of nodPQ and a new locus, saa. AB - The nitrogen-fixing symbiont Rhizobium meliloti establishes nodules on leguminous host plants. Nodulation (nod) genes used for this process are located in a cluster on the pSym-a megaplasmid of R. meliloti. These genes include nodP and nodQ (here termed nodPQ), which encode ATP sulfurylase and APS kinase, enzymes that catalyze the conversion of ATP and SO(4)2- into the activated sulfate form 3'-phosphoadenosine 5'-phosphosulfate (PAPS), an intermediate in cysteine synthesis. In Rhizobium, PAPS is also a precursor for sulfated and N-acylated oligosaccharide Nod-factor signals that cause symbiotic responses on specific host plants such as alfalfa. We previously found a highly conserved second copy of nodPQ in R. meliloti. We report here the mapping and cloning of this second copy, and its location on the second megaplasmid, pSym-b. The function of nodP2Q2 is equivalent to that of nodP1Q1 in complementation tests of R. meliloti and Escherichia coli mutants in ATP sulfurylase and adenosine 5'-phosphosulfate (APS) kinase. Mutations in nodP2Q2 do not have as severe an effect on symbiosis or plant host range as do those in nodP1Q1, however, possibly reflecting differences in expression and/or channeling of metabolites to specific enzymes involved in sulfate transfer. Strains mutated or deleted for both copies of nodQ are severely defective in symbiotic phenotypes, but remain prototrophic. This suggests the existence in R. meliloti of a third locus for ATP sulfurylase and APS kinase activities. We have found a new locus saa (sulfur amino acid), which may also encode these activities. PMID- 1459443 TI - The influence of local DNA sequence and DNA repair background on the mutational specificity of 1-nitroso-8-nitropyrene in Escherichia coli: inferences for mutagenic mechanisms. AB - We have examined the mutational specificity of 1-nitroso-8-nitropyrene (1,8 NONP), an activated metabolite of the carcinogen 1,8-dinitropyrene, in the lacI gene of Escherichia coli strains which differ with respect to nucleotide excision repair (+/- delta uvrB) and MucA/B-mediated error-prone translesion synthesis (+/ pKM101). Several different classes of mutation were recovered, of which frameshifts, base substitutions, and deletions were clearly induced by 1,8-NONP treatment. The high proportion of point mutations (> 92%) which occurred at G.C sites correlates with the percentage of 1,8-NONP-DNA adducts which occur at the C(8) position of guanine. The most prominent frameshift mutations were -(G.C) events, which were induced by 1,8-NONP treatment in all strains, occurred preferentially in runs of guanine residues, and whose frequency increased markedly with the length of the reiterated sequence. Of the base substitution mutations G.C-->T.A transversions were induced to the greatest extent by 1,8 NONP. The distribution of the G.C-->T.A transversions was not influenced by the nature of flanking bases, nor was there a strand preference for these events. The presence of plasmid pKM101 specifically increased the frequency of G.C-->T.A transversions by a factor of 30-60. In contrast, the -(G.C) frameshift mutation frequency was increased only 2-4-fold in strains harboring pKM101 as compared to strains lacking this plasmid. There was, however, a marked influence of pKM101 on the strand specificity of frameshift mutation; a preference was observed for -G events on the transcribed strand. The ability of the bacteria to carry out nucleotide excision repair had a strong effect on the frequency of all classes of mutation but did not significantly influence either the overall distribution of mutational classes or the strand specificity of G.C-->T.A transversions and (G.C) frameshifts. Deletion mutations were induced in the delta uvr, pKM101 strain. The endpoints of the majority of the deletion mutations were G.C rich and contained regions of considerable homology. The specificity of 1,8-NONP-induced mutation suggests that DNA containing 1,8-NONP adducts can be processed through different mutational pathways depending on the DNA sequence context of the adduct and the DNA repair background of the cell. PMID- 1459444 TI - Donor locus selection during Saccharomyces cerevisiae mating type interconversion responds to distant regulatory signals. AB - Mating type interconversion in homothallic strains of the yeast Saccharomyces cerevisiae results from directed transposition of a mating type allele from one of the two silent donor loci, HML and HMR, to the expressing locus, MAT. Cell type regulates the selection of the particular donor locus to be utilized during mating type interconversion: MATa cells preferentially select HML alpha and MAT alpha cells preferentially select HMRa. Such preferential selection indicates that the cell is able to distinguish between HML and HMR during mating type interconversion. Accordingly, we designed experiments to identify those features perceived by the cell to discriminate HML and HMR. We demonstrate that discrimination does not derive from the different structures of the HML and HMR loci, from the unique sequences flanking each donor locus nor from any of the DNA distal to the HM loci on chromosome III. Moreover, we find that the sequences flanking the MAT locus do not function in the preferential selection of one donor locus over the other. We propose that the positions of the donor loci on the left and right arms of chromosome III is the characteristic utilized by the cell to distinguish HML and HMR. This positional information is not generated by either CEN3 or the MAT locus, but probably derives from differences in the chromatin structure, chromosome folding or intranuclear localization of the two ends of chromosome III. PMID- 1459445 TI - Spontaneous amplification of the ADH4 gene in Saccharomyces cerevisiae. AB - Five spontaneous amplifications of the ADH4 gene were identified among 1,894 antimycin A-resistant mutants isolated from a diploid strain after growth at 15 degrees. Four of these amplifications are approximately 40-kb linear extrachromosomal palindromes carrying telomere homologous sequences at each end similar to a previously isolated amplification. ADH4 is located at the extreme left end of chromosome VII, and the extrachromosomal fragments appear to be the fusion of two copies of the end of this chromosome. The fifth amplification is a chromosomal amplification carrying an extra copy of ADH4 on both homologs of chromosome VII. These results suggest that the ADH system can be used to study amplification in Saccharomyces cerevisiae. PMID- 1459446 TI - The CCR4 protein from Saccharomyces cerevisiae contains a leucine-rich repeat region which is required for its control of ADH2 gene expression. AB - The CCR4 gene from Saccharomyces cerevisiae is required for the transcription of the glucose-repressible alcohol dehydrogenase (ADH2). Mutations in CCR4 also suppress the transcription at the ADH2 and his4-912delta loci caused by defects in the SPT10 (CRE1) and SPT6 (CRE2) genes. The CCR4 gene was mapped to the left arm of chromosome I and cloned by complementation of function using previously isolated segments of chromosome I. DNA sequence analysis of the cloned gene defined CCR4 as a 2511 bp open reading frame that would encode a polypeptide of 837 amino acids. The CCR4 mRNA was found to be 2.8 kb in size and Western analysis identified CCR4 as a 95,000 D protein. Disruption of the CCR4 gene resulted in reduced levels of ADH2 expression under both glucose and ethanol growth conditions and in temperature sensitive growth on nonfermentative medium, phenotypes essentially indistinguishable from previously identified mutations in CCR4. The amino terminus of the CCR4 protein was found to be rich in glutamine residues similar to a number of genes which are required for transcription. More importantly, CCR4 showed similarity to a diverse set of proteins sharing a leucine-rich tandem repeat motif, the presence of which has been implicated in mediating protein-protein interactions. Deletions of several of the five leucine rich repeats in CCR4 were shown to produce nonfunctional proteins indicating the importance of the repeats to CCR4 activity. This leucine-rich repeat region may mediate the contact CCR4 makes with another factor. PMID- 1459447 TI - Isolation and characterization of two Saccharomyces cerevisiae genes encoding homologs of the bacterial HexA and MutS mismatch repair proteins. AB - Homologs of the Escherichia coli (mutL, S and uvrD) and Streptococcus pneumoniae (hexA, B) genes involved in mismatch repair are known in several distantly related organisms. Degenerate oligonucleotide primers based on conserved regions of E. coli MutS protein and its homologs from Salmonella typhimurium, S. pneumoniae and human were used in the polymerase chain reaction (PCR) to amplify and clone mutS/hexA homologs from Saccharomyces cerevisiae. Two DNA sequences were amplified whose deduced amino acid sequences both shared a high degree of homology with MutS. These sequences were then used to clone the full-length genes from a yeast genomic library. Sequence analysis of the two MSH genes (MSH = mutS homolog), MSH1 and MSH2, revealed open reading frames of 2877 bp and 2898 bp. The deduced amino acid sequences predict polypeptides of 109.3 kD and 109.1 kD, respectively. The overall amino acid sequence identity with the E. coli MutS protein is 28.6% for MSH1 and 25.2% for MSH2. Features previously found to be shared by MutS homologs, such as the nucleotide binding site and the helix-turn helix DNA binding motif as well as other highly conserved regions whose function remain unknown, were also found in the two yeast homologs. Evidence presented in this and a companion study suggest that MSH1 is involved in repair of mitochondrial DNA and that MSH2 is involved in nuclear DNA repair. PMID- 1459448 TI - HTS1 encodes both the cytoplasmic and mitochondrial histidyl-tRNA synthetase of Saccharomyces cerevisiae: mutations alter the specificity of compartmentation. AB - Genetic and biochemical evidence shows that a single nuclear gene HTS1 encodes both the mitochondrial and cytoplasmic histidyl-tRNA synthetases (Hts). The gene specifies two messages, one with two in-frame ATGs (-60 and +1) and another with only the downstream ATG (+1). We have made a new set of mutations that enables us to express only the mitochondrial or the cytoplasmic form and compared the subcellular distribution of the Hts1 protein in these mutants and wild type, using an antibody that interacts with both the mitochondrial and cytoplasmic Hts1 as well as Hts1::LacZ fusions. Mutations in the upstream ATG (-60) or frameshift mutations in the presequence affect only the mitochondrial enzyme and not the cytoplasmic enzyme. Mutations in the downstream ATG (+1 ATG to ATC) destroy the function of the cytosolic enzyme, but do not affect the function of the mitochondrial enzyme. Overexpression of this construct restores cytoplasmic function. Cells expressing a truncated form of Hts containing a deletion of the first 20 amino-terminal residues (Htsc) produce a functional cytoplasmic enzyme, which does not provide mitochondrial function. Overexpression of this truncated cytoplasmic protein provides mitochondrial function and produces detectable levels of the synthetase in the mitochondrion. These experiments suggest that Hts1 contains two domains that together allow efficient localization of Htsm to the mitochondrion: an amino-terminal presequence in the mitochondrial precursor that is likely cleaved upon delivery to the mitochondrion and a second amino terminal sequence (residues 21-53) present in both the precursor and the cytoplasmic form. Neither one by itself is sufficient to act as an efficient mitochondrial targeting signal. Using our antibody we have been able to detect a protein of increased molecular mass that corresponds to that of the predicted precursor. Taken together these studies show that the specificity of compartmentation of the Hts protein depends upon both the primary sequence and the concentration of the protein in the cell. PMID- 1459449 TI - Loss of N-myc function results in embryonic lethality and failure of the epithelial component of the embryo to develop. AB - myc genes are thought to function in the processes of cellular proliferation and differentiation. To gain insight into the role of the N-myc gene during embryogenesis, we examined its expression in embryos during postimplantation development using RNA in situ hybridization. Tissue- and cell-specific patterns of expression unique to N-myc as compared with the related c-myc gene were observed. N-myc transcripts become progressively restricted to specific cell types, primarily to epithelial tissues including those of the developing nervous system and those in developing organs characterized by epithelio-mesenchymal interaction. In contrast, c-myc transcripts were confined to the mesenchymal compartments. These data suggest that c-myc and N-myc proteins may interact with different substrates in performing their function during embryogenesis and suggest further that there are linked regulatory mechanisms for normal expression in the embryo. We have mutated the N-myc locus via homologous recombination in embryonic stem (ES) cells and introduced the mutated allele into the mouse germ line. Live-born heterozygotes are under-represented but appear normal. Homozygous mutant embryos die prenatally at approximately 11.5 days of gestation. Histologic examination of homozygous mutant embryos indicates that several developing organs are affected. These include the central and peripheral nervous systems, mesonephros, lung, and gut. Thus, N-myc function is required during embryogenesis, and the pathology observed is consistent with the normal pattern of N-myc expression. Examination of c-myc expression in mutant embryos indicates the existence of coordinate regulation of myc genes during mouse embryogenesis. PMID- 1459450 TI - Embryonic lethality in mice homozygous for a targeted disruption of the N-myc gene. AB - The N-myc gene encodes a putative transcription factor that is thought to function in the regulation of gene expression during cell differentiation and/or growth. To examine the role of N-myc during development, we have used targeted mutagenesis in embryonic stem cells to produce a mouse line that carries an N-myc null allele. Mice homozygous for the mutation died between 10.5 and 12.5 days of gestation. Histological analysis of mutant embryos revealed that organs and tissues expected at these stages of development were present. However, multiple defects were observed, primarily in tissues and organs that normally express N myc. In particular, mutant hearts were underdeveloped, often retaining the S shape more typical of 9-day-old embryos. In addition, cranial and spinal ganglia were reduced in size and/or cellularity. Most of the noted defects were more consistent with a role of N-myc in proliferation of precursor populations than with a block in differentiation per se, at least at these early stages. These results demonstrate that N-myc plays an essential role during development and clearly confirm that N-myc has a physiological function that is distinct from that of the other myc-family genes. PMID- 1459451 TI - Mechanism of transcriptional antirepression by GAL4-VP16. AB - Promoter- and enhancer-binding factors appear to function by facilitating the transcription reaction as well as by counteracting chromatin-mediated repression (antirepression). We have examined the mechanism by which a hybrid activator, GAL4-VP16, is able to counteract histone H1-mediated repression by using both H1 DNA complexes and reconstituted H1-containing chromatin templates. The GAL4 DNA binding domain alone was sufficient to disrupt local H1-DNA interactions, but a transcriptional region was additionally necessary for antirepression. GAL4-VP16 mediated antirepression required an auxiliary factor, denoted as a co antirepressor, which was partially purified from Drosophila embryos. We have found that the co-antirepressor activity was sensitive to digestion with RNase A. Moreover, total RNA from Drosophila embryos could partially substitute for the co antirepressor fraction, which indicated that the co-antirepressor may function as a histone acceptor ("histone sink"). These findings suggest a model for gene activation in which sequence-specific transcription factors disrupt H1-DNA interactions at the promoter to facilitate transfer of H1 to a histone acceptor, which then allows access of the basal transcription factors to the DNA template. PMID- 1459452 TI - Initiation on chromatin templates in a yeast RNA polymerase II transcription system. AB - Templates were prepared with either the TATA box or transcription start sites of the yeast CYC1 promoter in a nucleosome. In both cases, initiation in an unfractionated yeast RNA polymerase II transcription system was abolished by the nucleosome. The inhibition appeared to be relieved by the activator protein Gal4 VP16 binding to a site upstream of the promoter. Inhibition was not relieved, however, in a transcription system reconstituted from purified components, indicating a requirement for additional factors for the effect of Gal4-VP16. PMID- 1459453 TI - Evidence that SNF2/SWI2 and SNF5 activate transcription in yeast by altering chromatin structure. AB - Changes in chromatin structure have frequently been correlated with changes in transcription. However, the cause-and-effect relationship between chromatin structure and transcription has been hard to determine. In addition, identifying the proteins that regulate chromatin structure has been difficult. Recent evidence suggests that a functionally related set of yeast transcriptional activators (SNF2/SWI2, SNF5, SNF6, SWI1, and SWI3), required for transcription of a diverse set of genes, may affect chromatin structure. We now present genetic and molecular evidence that at least two of these transcriptional activators, SNF2/SWI2 and SNF5, function by antagonizing repression mediated by nucleosomes. First, the transcriptional defects in strains lacking these SNF genes are suppressed by a deletion of one of the two sets of genes encoding histones H2A and H2B, (hta1-htb1) delta. Second, at one affected promoter (SUC2), chromatin structure is altered in snf2/swi2 and snf5 mutants, and this chromatin defect is suppressed by (hta1-htb1) delta. Finally, analysis of chromatin structure at a mutant SUC2 promoter, in which the TATA box has been destroyed, demonstrates that the differences in SUC2 chromatin structure between SNF5+ and snf5 mutant strains are not simply an effect of different levels of SUC2 transcription. Thus, these results strongly suggest that SNF2/SWI2 and SNF5 cause changes in chromatin structure and that these changes allow transcriptional activation. PMID- 1459454 TI - Drosophila C/EBP: a tissue-specific DNA-binding protein required for embryonic development. AB - Recently, we reported the cloning of the Drosophila melanogaster homolog of the vertebrate CCAAT/enhancer-binding protein (C/EBP). Here, we describe studies of the DNA-binding and dimerization properties of Drosophila C/EBP (DmC/EBP), as well as its tissue distribution, developmental regulation, and essential role in embryonic development and conclude that it bears functional as well as structural similarity to mammalian C/EBP. DmC/EBP contains a basic region/leucine zipper (bZIP) DNA-binding domain very similar to that of mammalian C/EBP and the purified C/EBPs bound to DNA with the same sequence specificity. Among the DNA sequences that DmC/EBP bound with high affinity was a conserved site within the promoter of the DmC/EBP gene itself. In vitro, DmC/EBP and mammalian C/EBP specifically formed functional heterodimers; however, as we found no evidence for a family of DmC/EBPs, DmC/EBP may function as a homodimer in vivo. The DmC/EBP protein was expressed predominantly during late embryogenesis in the nuclei of a restricted set of differentiating cell types, such as the lining of the gut and epidermis, similar to the mammalian tissues that express C/EBP. We have characterized mutations in the DmC/EBP gene and found that deleting the gene caused late embryonic lethality. Embryos that lack C/EBP die just before or just upon hatching. The lethal phenotype of C/EBP mutants can be rescued with the cloned C/EBP gene introduced by P-element-mediated germ-line transformation. The strict requirement for C/EBP during Drosophila embryogenesis, coupled with its structural and functional similarities to mammalian C/EBP, provides a useful genetic system in which to study the role of C/EBP in development. PMID- 1459455 TI - Pumilio is essential for function but not for distribution of the Drosophila abdominal determinant Nanos. AB - The Drosophila gene pumilio is expressed maternally, and its function is essential during early embryogenesis for the formation of abdominal segments. Our molecular analysis reveals that pumilio is a large gene that encodes a protein of 160 kD whose RNA is enriched at the posterior pole of the egg. As with pumilio, the maternal effect gene nanos is specifically required for abdomen formation. The Nanos protein is expressed in a posterior-to-anterior concentration gradient in the developing embryo. Previous experiments demonstrated a genetic interaction between pumilio and nanos, and led to the suggestion that pumilio is required for the proper spatial distribution of the Nanos protein. Here, we show that the expression and distribution of nanos RNA and protein in embryos derived from pumilio mutant females are indistinguishable from wild type. We conclude that abdomen formation depends both on Nanos activity, spreading from the localized posterior source, and on Pumilio activity, present throughout the embryo. PMID- 1459456 TI - Transcription factors junB and c-jun are selectively up-regulated and functionally implicated in fibrosarcoma development. AB - Bovine papillomavirus transgenic mice develop skin tumors arising from dermal fibroblasts in a process comprised of three distinctive stages: mild and aggressive fibromatoses, and fibrosarcoma. In both tissue biopsies and derivative cell lines, the proto-oncogenes junB and c-jun are induced in the latter two stages, in contrast to junD and fos. Fibrosarcoma cell lines have increased AP-1 DNA-binding activity. Overexpression of junB or c-jun by transfection into the mild fibromatosis stage elicited changes in cell shape and anchorage independence, whereas junD did not. Similar transfections of normal skin fibroblasts had no effect. Thus, junB and c-jun represent progression factors whose activities are necessary at an intermediate stage of tumor development, subsequent to the initiation of aberrant proliferation. PMID- 1459457 TI - The proto-oncogene bcl-3 encodes an I kappa B protein. AB - The bcl-3 gene product, overexpressed in chronic lymphocytic leukemia (CLL) patients with the translocation t(14;19), is a member of the I kappa B family. The bcl-3 protein is able to inhibit the DNA binding and trans-activation of authentic NF-kappa B heterodimers p50-p65 and p49-p65, as well as p50 and p49 homodimers. The bcl-3 protein does not inhibit either the DNA-binding activity of the Rel protein or its ability to trans-activate genes linked to the kappa B site. A human 37-kD protein (I kappa B alpha), identified previously as a member of the I kappa B family, is also unable to inhibit DNA-binding activity of the Rel protein. However, unlike bcl-3, the 37-kD (I kappa B alpha) protein has no effect on the DNA-binding activity of p50 or p49 homodimers. Two dimensional phosphotryptic peptide maps of the human bcl-3 and the human 37-kD (I kappa B alpha) proteins reveal that the phosphopeptides from the 37-kD (I kappa B alpha) protein are nested within the bcl-3 protein. Furthermore, bcl-3 antisera immunoprecipitates an in vitro-radiolabeled 37-kD (I kappa B alpha) protein. Proteins of 56 and 38 kD can be identified in HeLa cells stimulated with PMA and immunoprecipitated with bcl-3 antisera. Comparison of tryptic peptide maps of the bcl-3 protein synthesized in vitro, and p56 and p38 from HeLa cells, shows that they are all structurally related. Removal of the amino-terminal sequences of the bcl-3 protein generates a protein that inhibits the DNA binding of the p50-p65 heterodimer but, like the 37-kD (I kappa B alpha) protein, is no longer able to inhibit the binding of the p50 and p49 homodimers with kappa B DNA. We propose that the bcl-3 and 37-kD (I kappa B alpha) proteins are related and are members of the I kappa B family. PMID- 1459458 TI - Serine-to-alanine substitutions at the amino-terminal region of phytochrome A result in an increase in biological activity. AB - We have used a tobacco transgenic plant system to assay the structure/function relationship of phytochrome A (phyA), a plant photoreceptor. The amino terminus of phyA from different plant species is very rich in serine residues. To investigate whether these serine residues are required for phytochrome function, the first 10 serine codons encoding amino acid residues 2-4, 10-14, 19, and 20 in the amino-terminal domain of the rice phyA gene (phyA) were changed to alanine codons. The mutant (S/A phyA), as well as the wild-type phyA cDNA, was placed under the control of the 35S promoter, and the chimeric genes were transferred into the tobacco genome by Agrobacterium-mediated transformation. Transgenic tobacco plants expressing either wild-type or S/A phyA showed similar phenotypic alterations, including dwarfism and dark-green leaves. However, hypocotyl elongation experiments revealed that transgenic seedlings expressing S/A phyA showed a higher amplitude of the red light response with respect to the inhibition of hypocotyl elongation. The observed difference is not correlated with expression levels of the transgene. The chromophore is attached to the mutant phyA apoprotein (PHY A), and the mutant photoreceptor is photoreversible, giving a difference spectrum indistinguishable from that of the rice phyA. Our results indicate that the S/A mutant has a higher biological activity as compared with the wild-type rice phyA. PMID- 1459459 TI - Developmental and light regulation of eas, the structural gene for the rodlet protein of Neurospora. AB - The surface of many fungal spores is covered by a hydrophobic sheath termed the rodlet layer. We have determined that the rodlet protein of Neurospora crassa is encoded by a cloned gene designated bli-7, and that bli-7 is identical to the known gene eas (easily wettable). Using eas DNA as a probe we show that eas mRNA is abundant in illuminated mycelia and conidiophores but is not detectable or is barely detectable in dark-grown mycelia, mature macroconidia, microconidia, and ascospores. Mutations in the genes acon-2, acon-3, and fl block early conidiophore development; of these, only fl prevents normal eas transcription. The EAS protein is homologous to the rodlet protein (RodA) of Aspergillus nidulans, and the hydrophobins of Schizophyllum commune. eas is the first cloned conidiation (con) gene of N. crassa that is associated with a phenotypic alteration. PMID- 1459460 TI - The Neurospora circadian clock-controlled gene, ccg-2, is allelic to eas and encodes a fungal hydrophobin required for formation of the conidial rodlet layer. AB - The Neurospora crassa clock-controlled gene (ccg-2) is transcriptionally activated by the circadian clock in a time-of-day-specific manner. Transcript and sequence analyses of ccg-2 reveal that the predicted Ccg-2 polypeptide bears significant similarity to a class of low-molecular-weight, cysteine-rich, hydrophobic proteins (hydrophobins), first identified in Schizophyllum, and including the product of the developmentally regulated Aspergillus gene, rodletless, required for spore surface rodlets. Allelism between ccg-2 and easily wettable (eas) (one of the first developmental genetic loci identified in Neurospora) was predicted on the basis of this similarity, their close genetic linkage, and previous findings demonstrating that eas mutants lack rodlets. In this study allelism is confirmed experimentally by showing that (1) transformation of an eas mutant strain with ccg-2 DNA results in phenotypic complementation, including restoration of surface rodlets, (2) inactivation of the ccg-2 gene, by RIP, results in an eas phenotype including loss of rodlet fascicles, and (3) the original eas strain has dramatically reduced levels of ccg 2 mRNA. Thus, the clock-controlled ccg-2 gene encodes an integral component of fungal asexual spores important for spore dispersal. The dramatic reduction of ccg-2 expression in the eas mutant has no apparent effect on the normal operation of the circadian clock, confirming that there is no feedback of this clock output on the oscillator itself. These data, in conjunction with the previous observation that ccg-2 is light induced, serve to focus attention on the dual interacting role of light and the circadian clock in the regulation of fungal spore development. PMID- 1459461 TI - A temporally controlled sigma-factor is required for polar morphogenesis and normal cell division in Caulobacter. AB - The transcription of many spatially and temporally controlled flagellar structural genes in Caulobacter requires the RNA polymerase sigma 54 subunit. Like flagellar biogenesis, stalk formation is an asymmetric polar morphogenesis that occurs once each cell cycle in response to internal cell cycle signals. We have isolated the sigma 54 gene (rpoN) and describe here a novel role for this alternative sigma-factor in cell differentiation: It is required for the biogenesis of both polar structures, and the disruption of the rpoN gene results in aberrant cell division. Surprisingly, the transcription of rpoN is temporally regulated during the cell cycle; it increases 10-fold commensurate with stalk formation and just before the onset of flagellar gene expression. These results suggest that sigma 54 abundance responds to cell cycle cues and is involved in the global timing of the central events of Caulobacter development, whereas the transcriptional activators of sigma 54-dependent promoters are responsible for the refined control of the expression of individual or small groups of genes required for each specific event. PMID- 1459462 TI - Transcriptional control via translational repression by c4 antisense RNA of bacteriophages P1 and P7. AB - The c4 repressors of bacteriophages P1 and P7 are antisense RNAs that inhibit antirepressor synthesis. This antisense inhibition is unusual in that the c4 repressor and the repressed genes orfx and ant are cotranscribed in that order from the same promoter, and c4 RNA is processed from a precursor RNA. Here, we show that c4 RNA directly represses translation of orfx, a small open reading frame, to which ant is translationally coupled. This translational repression blocks ant transcription via a rho-dependent terminator. Thus, c4 RNA controls expression of the ant gene by a novel indirect mechanism combining translational repression, translational coupling, and rho-dependent termination. PMID- 1459463 TI - Biphasic effect of Max on Myc cotransformation activity and dependence on amino- and carboxy-terminal Max functions. AB - In Ras cotransformation assays, Max exhibited a biphasic effect on Myc transformation activity. Cotransfection of low levels of Max expression plasmid stimulated Myc transformation activity, but cotransfection of high levels suppressed it. Mutations in the functionally undefined Max amino- and carboxy terminal regions outside of the B/HLH/LZ motif partly separated these activities, suggesting various modes of Max regulation. We demonstrate that the Max protein is a nuclear protein in vivo and identify a carboxy-terminal region similar to nuclear localization signals whose integrity is necessary for efficient localization. Two mutants that delete amino- or carboxy-terminal consensus signals for casein kinase II (CKII) exhibited altered gel mobility and DNA binding potential in vitro and showed modified transforming potential in the Ras cotransformation assay, suggesting that CKII or a CKII-related enzyme may regulate Max function in vivo. Our data suggest that both the ratio of Myc/Max hetero-oligomers to Max homo-oligomers and Max-specific regulation can contribute to determining the biological activity of Myc in vivo. PMID- 1459464 TI - Putting the heat on sex determination. AB - Sex determination and differentiation are inherently fascinating to both layperson and geneticist. Major advances have accelerated interest in the molecular genetic events mediating these processes in nematodes, flies, mice and humans. Far less attention has been paid to those organisms, particularly reptiles, where sex is determined by environmental cues. However, recent experimental evidence suggests that the two modes of sex determination may not only share common genetic elements, but may also be regulated by similar mechanisms. We argue that the ability to manipulate sex by temperature provides a particularly suitable model for exploring the molecular basis of this fundamental biological process. PMID- 1459465 TI - Evolution of pericentromeric heterochromatin of human X chromosome. AB - An unusual large heterochromatic segment around the pericentromeric region of the X-chromosome is reported. In normal circumstances, the pericentromeric region of the X-chromosome is negative by the restriction endonuclease AluI/Giemsa technique. However, this unusual X-chromosome was found to have AluI resistant (positive) chromatin. The evolution of extra heterochromatin is a postzygotic event as substantiated by the presence of a normal cell line. PMID- 1459467 TI - Accumulation of amyloid precursor protein and beta-protein immunoreactivities in axons injured by cerebral infarct. AB - To determine the distribution of amyloid precursor protein (APP), monoclonal antibodies against APP45-62 (APP1-28-9) and beta1-17 (4A18 and 4A61) were produced. In the sections of Alzheimer's disease (AD) brain, APP1-28-9 was reactive with neurites around senile plaques and a few neurons but not with amyloid cores. This antibody also immunostained the axons in the ischemic lesions of brain tissues from cases with cerebral infarct. 4A18 and 4A61 were reactive with amyloid plaques but not with neurites and neurons. The latter two antibodies also immunostained axons in ischemic lesions. These findings suggest that APP, transported by the fast axonal flows, accumulated in the injured axons in the central nervous system. The beta immunoreactivity appearing in those axons may provide a clue to the mechanism of amyloidogenesis. PMID- 1459466 TI - Nucleotide sequence analysis of a mouse Y chromosomal DNA fragment containing Bkm and LINE elements. AB - The strong suppression of crossing-over between the X and Y chromosomes permits rapid accumulation of repetitive sequences in the Y chromosome. To gain insight into the mechanism responsible for the sequence amplification, it is essential to characterize Y chromosomal repetitive sequences at the molecular level. Here, we report the entire nucleotide sequence (3,902bp) of AC11, a mouse sequence that is repeated 300 times in the Y chromosome. AC11 is AT rich (32.8% GC), and contains many short poly(A) sequences. In addition, it has Bkm and LINE sequences as well as a Y chromosome-specific sequence. The Bkm sequence consists of typical (GATA) and (GACA) repeating units, whereas the LINE sequence deviates considerably from other mouse LINE sequences (71-76% identity) and may be considered atypical. The Y chromosome-specific region seems to be unique and does not identify similar sequences in the GenBank library. The information obtained from the nucleotide sequence should form the foundation to study the evolutionary processes through which AC11-related sequences have accumulated in the mouse Y chromosome. PMID- 1459468 TI - Alzheimer's disease beta-amyloid precursor protein in rat neural cells in culture. AB - Immunochemical studies were performed on Alzheimer's beta-amyloid precursor protein (APP) in rat brain and cultured rat neural cells. Multiple APP subtypes were detected on immunoblots of brain homogenate with several antisera specific for subsequences of APP. In rat neural cell cultures, it was demonstrated that the composition of APP subtypes differed among cell types and subcellular fractions, and that APP subtypes in PC12h cells varied in their heparin binding affinity, suggesting distinct functional roles for different APP subtypes. Compatible with the possible role of APP in cell-matrix interaction, an increase in oligodendroglial APP was observed following their attachment onto poly-L lysine substratum. PMID- 1459469 TI - Circulating suppressing factor for the muscarinic acetylcholine receptor in patients with senile dementia of the Alzheimer type. AB - Circulating suppressing factor for the binding of quinuclidinyl benzilate (QNB), an antagonist for the muscarinic acetylcholine receptor, to the synaptic membranes was evaluated in 48 patients with senile dementia of the Alzheimer type (SDAT), in 17 patients with the vascular type dementia (VTD) and in 11 nondemented elderly subjects (NE). The mean suppression rate on the binding in the SDAT group was significantly greater than that in the NE group, although that in the VTD group was similar to that in the NE group. Moreover, the percent QNB binding was significantly (p < 0.05) correlated with the score of the mini-mental state in the SDAT group. The circulating suppressing factor may participate in the pathogenesis of SDAT. PMID- 1459470 TI - Production of endothelin-1 in vascular endothelial cells is regulated by factors associated with vascular injury. AB - We studied the effects of factors associated with vascular injury on the production of endothelin-1 (ET-1) in cultured porcine aortic endothelial cells. ET-1 mRNA expression and peptide production in endothelial cells were increased by thrombin, transforming growth factor beta 1 (TGF beta 1), interleukin-1 (IL-1) and tumor necrotizing factor alpha (TNF alpha). The analysis of the enhancer/promoter region of the human ET-1 gene showed that the ET-1 gene transcription is regulated in a cell-specific manner and is activated by thrombin, TGF beta 1 and IL-1. These results suggest that the production of ET-1 in endothelial cells is regulated by factors associated with platelet aggregation, macrophage infiltration and the formation of atherosclerotic lesions. PMID- 1459471 TI - Expression of glucose transporter isoforms with aging. AB - To elucidate the cellular mechanisms for impairment of glucose metabolism associated with aging, the facilitative glucose transporter protein and mRNA were studied in various tissues of young (7-week-old) and aged (20-month-old) rats. GLUT4 glucose transporter protein, a major glucose transporter isoform in the insulin-responsive tissues, was selectively decreased in the epididymal fat tissues of the aged rats compared with the young rats. This decrease is likely to be due to a decrease in protein synthesis rather than in protein stability, since GLUT4 mRNA per unit cellular total RNA was also decreased. GLUT4 mRNA in the skeletal muscle was rather increased in spite of the decreased level of GLUT4 protein in the aged rats, suggesting that the translational efficiency and/or stability of GLUT4 protein is decreased in the skeletal muscle of the aged rats compared with the young rats. In contrast to these alterations in GLUT4 expression, no apparent decrease in the GLUT1 protein amount was observed in the fat tissues, skeletal muscle and brain of the aged rats compared with the young rats. Thus, the tissue and isoform-specific alterations in glucose transporter expression are associated with aging and may contribute to impairment of glucose metabolism observed with aging. PMID- 1459472 TI - Human platelet-derived transforming growth factor-beta stimulates synthesis of glycosaminoglycans in cultured porcine aortic endothelial cells. AB - Human platelet-derived transforming growth factor-beta (TGF-beta) stimulated the incorporation of [35S]sulfate into glycosaminoglycans (GAGs) both in the medium and on the cell surface of cultured aortic endothelial cells in a dose- and time dependent manner. TGF-beta inhibited the suppression of GAG synthesis by other cytokines. TGF-beta increased the protein synthesis, while reducing the DNA synthesis by endothelial cells. The proportion of anticoagulant heparan sulfate in total GAGs was reduced. Thus, TGF-beta affected the endothelial GAG metabolism both quantitatively and qualitatively. PMID- 1459473 TI - Genetic and environmental factors of bone mineral density indicated in Japanese twins. AB - To evaluate the effects of genetic and environmental factors on the bone mass, we determined the bone mineral density (BMD) in the total body, the lumbar spine and in the femoral neck in 23 Japanese twin pairs including 21 monozygotic (MZ) pairs, applying dual-energy X-ray absorptiometry. In MZ pairs aged 20-49 years, highly significant intraclass correlation coefficients, ranging from 0.775 to 0.926, were observed at several sites, including the lumbar spine and the femoral neck, which suggests considerable contributions of genetic factors to the BMD. Neither intraclass correlation coefficients nor intrapair differences were found to change with increasing age in the present analysis. In female MZ pairs, exercises both at the present time and in the past were correlated with the BMD at several sites as well as body mass index in multiple regression analyses. PMID- 1459474 TI - Nitroxide-mediated protection against X-ray- and neocarzinostatin-induced DNA damage. AB - The stable free radical Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidinyloxy) has been shown to protect against X-ray-induced cytotoxicity and hydrogen peroxide- or xanthine oxidase-induced cytotoxicity and mutagenicity. The ability of Tempol to protect against X-ray- or neocarzinostatin (NCS)-induced mutagenicity or DNA double-strand breaks (dsb) was studied in Chinese hamster cells. Tempol (50 mM) provided a protection factor of 2.7 against X-ray-induced mutagenicity in Chinese hamster ovary (CHO) AS52 cells, with a protection factor against cytotoxicity of 3.5. Using the field inversion gel electrophoresis technique of measuring DNA dsb, 50 mM Tempol provides a threefold reduction in DNA damage at an X-ray dose of 40 Gy. For NCS-induced damage, Tempol increased survival from 9% to 80% at 60 ng/mL NCS and reduced mutation induction by a factor of approximately 3. DNA dsb were reduced by a factor of approximately 7 at 500 ng/mL NCS. Tempol is representative of a class of stable nitroxide free radical compounds that have superoxide dismutase-mimetic activity, can oxidize metal ions such as ferrous iron that are complexed to DNA, and may also detoxify radiation-induced organoperoxide radicals by competitive scvenging. The NCS chromophore is reduced by sulfhydryls to an active form. Electron spin resonance (ESR) spectroscopy shows that 2-mercaptoethanol-activated NCS reacts with Tempol 3.5 times faster than does unactivated NCS. Thus, Tempol appears to inactivate the NCS chromophore before a substantial amount of DNA damage occurs. PMID- 1459475 TI - MDA, oxypurines, and nucleosides relate to reperfusion in short-term incomplete cerebral ischemia in the rat. AB - Short-term incomplete cerebral ischemia (5 min) was induced in the rat by the bilateral clamping of the common carotid arteries. Reperfusion was obtained by removing carotid clamping and was carried out for the following 10 min. Animals were sacrificed either at the end of ischemia or reperfusion. Controls were represented by a group of sham-operated rats. Peripheral venous blood samples were withdrawn from the femoral vein from rats subjected to cerebral reperfusion 5 min before ischemia, at the end of ischemia, and 10 min after reperfusion. Neutralized perchloric acid extracts of brain tissue were analyzed by a highly sensitive high-performance liquid chromatography (HPLC) method for the direct determination of malondialdehyde, oxypurines, nucleosides, nicotinic coenzymes, and high-energy phosphates. In addition, plasma concentrations of malondialdehyde, hypoxanthine, xanthine, inosine, uric acid, and adenosine were determined by the same HPLC technique. Incomplete cerebral ischemia induced the appearance of a significant amount (8.05 nmol/g w.w.; SD = 2.82) of cerebral malondialdehyde (which was undetectable in control animals) and a decrease of ascorbic acid. A further 6.6-fold increase of malondialdehyde (53.30 nmol/g w.w.; SD = 17.77) and a 18.5% decrease of ascorbic acid occurred after 10 min of reperfusion. Plasma malondialdehyde, which was present in minimal amount before ischemia (0.050 mumol/L; SD = 0.015), significantly increased after 5 min of ischemia (0.277 mumol/L; SD = 0.056) and was strikingly augmented after 10 min of reperfusion (0.682 mumol/L; SD = 0.094). A similar trend was observed for xanthine, uric acid, inosine, and adenosine, while hypoxanthine reached its maximal concentration after 5 min of incomplete ischemia, being significantly decreased after reperfusion. From the data obtained, it can be concluded that tissue concentrations of malondialdehyde and ascorbic acid, and plasma levels of malondialdehyde, oxypurines, and nucleosides, reflect both the oxygen radical mediated tissue injury and the depression of energy metabolism, thus representing early biochemical markers of short-term incomplete brain ischemia and reperfusion in the rat. In particular, these results suggest the possibility of using the variation of malondialdehyde, oxypurines, and nucleosides in peripheral blood as a potential biochemical indicator of reperfusion damage occurring to postischemic tissues. PMID- 1459476 TI - Breath ethane: a specific indicator of free-radical-mediated lipid peroxidation following reperfusion of the ischemic liver. AB - A major component of the organ injury mediated by toxic oxidants, such as seen following reperfusion of the ischemic liver, is due to the peroxidation of polyunsaturated fatty acids, especially of cell membranes. We utilized the measurement of exhaled breath ethane, a metabolic product unique to oxidant mediated lipid peroxidation, as a noninvasive indicator of this process in swine liver subjected to warm ischemia/reperfusion. Under rigorously controlled anesthesia conditions, pig livers were subjected to 2 h of warm total ischemia, followed by reperfusion in situ. Expired air was collected and its ethane content quantitated by a novel gas chromatographic technique. The time course of breath ethane generation correlated closely with the appearance of hepatocellular injury as measured by impairment of Factor VII generation and other measures of liver integrity. Moreover, the administration of the specific superoxide free radical scavenger, superoxide dismutase (SOD), significantly attenuated both the elaboration of ethane and the hepatocellular injury. These findings not only provide confirmation of the previously reported link between hepatocellular injury by free radicals generated at reperfusion, but also establish the use of expired breath ethane analysis as a sensitive, specific, and noninvasive indicator of the injury process in real time. PMID- 1459477 TI - The inhibitory effects of 21 mimics of superoxide dismutase on luminol-mediated chemiluminescence emitted from PMA-stimulated polymorphonuclear leukocyte. AB - Four groups comprising 21 superoxide dismutase (SOD) mimics synthesized by us were comparatively studied for their inhibitory effects on luminol-mediated chemiluminescence emitted from phorbol myristate acetate (PMA)-stimulated polymorphonuclear leukocyte (PMNL). Among these groups, 20-membered macrocyclic bicopper(II) complexes and 13-membered macrocyclic dioxotetramine copper(II) complexes exhibited relatively higher activities of scavenging reactive oxygen species (ROS) produced by PMA-stimulated PMNL as compared with polyamine Cu(II) Zn(II) complexes and copper(II) complexes of bis-shiff-base. Moreover, distinctly different effects of SOD mimics in the biological system have been found even in the same group. It is suggested that the biological effects of some SOD mimics are related to their structures. PMID- 1459478 TI - Fenton reagents may not initiate lipid peroxidation in an emulsified linoleic acid model system. AB - This study includes two parts. First, the Fe2+ autooxidation and chelation processes in the presence of the chelators ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine pentaacetic acid (DTPA) were studied by measuring UV light absorbance alterations. Competition for Fe3+ between chelators and water or phosphate buffer (PB) ions was confirmed. The addition of EDTA or DTPA to Fe3+ in water or PB only slowly turned the water/PB-Fe3+ complexes to EDTA-Fe3+ or DTPA Fe3+ complexes. In the second part of this study, the initiation mechanisms of Tween 20 emulsified linoleic acid peroxidation under stimulation by chelator-Fe O2 complexes were studied by measuring changes in UV light absorbance following diene conjugation. Fe3+ in the presence of EDTA or DTPA did not stimulate diene conjugation. Fe2+ (0.10 mM) and EDTA (0.11 mM) stimulated diene conjugation of the linoleic acid emulsion, but only after apparent Fe2+ autooxidation. Fe2+ and DTPA, as well as premixed DTPA-Fe2+ complex, resulted in very fast diene conjugation in a wide range of concentrations. A nonlinear, mainly square root relation between Fe2+ concentration and peroxidation rate was noted. Superoxide dismutase (SOD), catalase, and mannitol did not prevent the lipid peroxidation. H2O2 substantially decreased the DTPA-Fe2+ stimulated, otherwise rapid, diene conjugation but slightly enhanced the slower one stimulated by EDTA-Fe2+. Without ambient oxygen, Fenton reagents did not result in .H abstraction-related diene conjugation. The findings suggest that .OH resulting from Fenton reagents may not be the main cause for the initiation of peroxidation in this model system. Furthermore, a study with different combinations of Fe2+ and Fe3+ did not support the Fe2+/Fe3+ (1:1) optimum ratio hypothesis. We therefore conclude that perferryl ions or chelator-Fe-O2 complexes may be responsible for the first-chain initiation of lipid peroxidation, at least in this model system. PMID- 1459479 TI - Use of essential metalloelement complexes or chelates in biological studies. PMID- 1459480 TI - Modification of reperfusion-induced ionic imbalance by free radical scavengers in spontaneously hypertensive rat retina. AB - We studied the effects of free radical scavengers, superoxide dismutase (SOD), vitamin E, and EGB 761, on ion shifts (Na+, K+, and Ca2+) induced by ischemia reperfusion in rat retina obtained from spontaneously hypertensive rats. Eyes were subjected to 90 min of retinal ischemia followed by 24 h of reperfusion. Two basic protocols were used: (1) chronic application, in which rats received SOD (7500, 15,000, and 30,000 U/kg, i.v.), vitamin E (50, 100, and 200 mg/kg, i.v.), and EGB 671 (50, 100, and 200 mg/kg, orally) for 10 d, respectively; and (2) acute administration, in which 7500, 15,000, and 30,000 U/kg of SOD, 50, 100, and 200 mg/kg of vitamin E, and 50, 100, and 200 mg/kg of EGB 761 were administered after an ischemic episode, at the onset of reperfusion, respectively. In the drug free control group, 90 min ischemia followed by 24 h of reperfusion resulted in an accumulation of retinal sodium and calcium from their nonischemic control values of 76 +/- 4 and 3.2 +/- 0.1 mumol/g dry weight to 112 +/- 6 (p < .001) and 6.2 (p < .001) mumol/g dry weight, respectively. Tissue potassium loss was also observed in this model of retinal ischemia reperfusion, and after 90 min ischemia followed by 24 h of reperfusion potassium content was significantly reduced from its nonischemic control value of 266 +/- 5 to 207 +/- 6 (p < .001) mumol/g dry weight. The chronic administration of SOD, vitamin E, and EGB 761 dose dependently reduced the reperfusion-induced ionic imbalance and improved the recovery of retinal ion contents.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459481 TI - Salicylate hydroxylation as an early marker of in vivo oxidative stress in diabetic patients. AB - In vivo metabolism of salicylic acid produces two main hydroxylated derivatives (2,5- and 2,3-dihydroxybenzoic acid). The former can be produced by enzymatic pathways through the cytochrome P-450 system, while the latter is reported to be solely formed by direct hydroxyl radical attack. Therefore, measurement of 2,3 dihydroxybenzoate, following oral administration of salicylate in its acetylated form (aspirin), has been proposed for assessment of oxidative stress. In this article we report plasma levels of 2,3- and 2,5-dihydroxybenzoates following the administration of 1 g aspirin and plasma levels of thiobarbituric acid-reactive material (TBARM) in well-controlled diabetic patients and in healthy subjects. 2,3-Dihydroxybenzoate levels were significantly higher (23%) in diabetic patients than in controls (63.4 +/- 20.1 versus 49.0 +/- 6.8 nM; p < .05). On the other hand, TBARM values were not significantly different between groups. These results suggest that the method is useful to reveal in vivo oxidative stress independently from the peroxidation of lipids, and they support the hypothesis that oxygen radicals are involved in the pathogenesis of chronic complications of diabetes. PMID- 1459482 TI - Trolox C, a lipid-soluble membrane protective agent, attenuates myocardial injury from ischemia and reperfusion. AB - The lipophilic antioxidant Trolox C, a vitamin E analog, was administered to isolated, buffer-perfused rabbit hearts subjected to 25 min of global stop-flow ischemia and 30 min of reperfusion. In six hearts, Trolox C (200 microM) was infused for 15 min immediately prior to ischemia and for the first 15 min of reperfusion. Six control hearts received only vehicle. Gas chromatography analysis confirmed that effective myocardial levels of Trolox were attained. At 30 min reperfusion, the recovery of left ventricular developed pressure was 56 +/ 3% of baseline in control hearts versus 70 +/- 4% in Trolox-treated hearts (p < .01). There was also significant improvement in recovery of Trolox-treated hearts in diastolic pressure and both maximum and minimum values of the first derivative of left ventricular pressure (dP/dt). Creatine phosphokinase release into the coronary effluent at 30 min of reperfusion was 16.5 +/- 8.4 IU/min in untreated and 6.3 +/- 1.0 IU/min (p < .05) in Trolox-treated hearts. Thus Trolox C, a lipophilic antioxidant, attenuated myocardial injury during stop-flow ischemia and reperfusion. PMID- 1459483 TI - Effect of oxidant stress on calcium signaling in vascular endothelial cells. AB - The endothelial cell is recognized as a critical modulator of blood vessel tone and reactivity. This regulatory function of endothelial cells occurs via synthesis and release of diffusible paracrine substances which induce contraction or relaxation of adjacent vascular smooth muscle. In response to stimulation by blood-borne agonists such as bradykinin or histamine, the endothelial cell utilizes cytosolic ionic Ca2+ as a trigger in the transduction of the stimulatory signal into a paracrine response. Considerable evidence has accumulated to indicate that various forms of biologically important oxidant stress alter vascular function in an endothelium-dependent manner. Further, oxidant stress is known to alter the mechanisms which govern Ca2+ homeostasis in the endothelial cell. Recently, we have described a model in which the oxidant tert butylhydroperoxide is utilized to examine the effects of oxidant stress on Ca(2+) dependent signal transduction in vascular endothelial cells. In this model, three temporal phases are evident and consist of (1) inhibition of the agonist stimulated Ca2+ influx pathway, (2) inhibition of receptor-activated release of Ca2+ from internal stores and elevation of resting cytosolic free Ca2+ concentration, and (3) progressive increase in resting cytosolic Ca2+ concentration and loss of responsiveness to agonist stimulation. In this review, the mechanisms which characterize agonist-stimulated Ca2+ signaling in vascular endothelial cells, and the effects of oxidant stress on signal transduction will be described. The mechanisms potentially responsible for oxidant-induced inhibition of Ca2+ signaling will be considered. PMID- 1459484 TI - Reactive oxygen intermediates and human immunodeficiency virus (HIV) infection. AB - HIV infection affects various parts of the immune system, including the CD4+ lymphocytes and mononuclear phagocytes, and causes a progressive immunodeficiency. This renders the patient susceptible to various opportunistic infections and neoplasms. Reactive oxygen intermediates (ROI) are important for the intracellular killing of microorganisms by mononuclear phagocytes and neutrophils. Although data are discrepant, several studies suggest that the generation of ROI is impaired in mononuclear phagocytes, and possibly also in neutrophils, from HIV-infected individuals. This may lead to deficient killing of intracellular microorganisms predisposing the HIV-infected patient to certain opportunistic infections. Recently, in vitro studies have shown that ROI activate the intracellular transcription factor nuclear factor kappa B (NF-kappa B) which stimulates HIV replication. Intracellular antioxidant systems, such as the glutathione system, seem to be of importance for the regulation of ROI levels and thus probably for HIV replication in vitro. However, the role of ROI in regulation of HIV replication in vivo is unknown at present. The role of ROI in HIV infection is thus difficult to assess, both at the cellular and clinical level. Reduced intracellular concentrations of ROI may lead to impaired phagocyte microbicidal functions, thus predisposing HIV-infected patients to various opportunistic infections. On the other hand, increased ROI levels may be associated with a stimulation of HIV replication leading to clinical deterioration. PMID- 1459485 TI - Effects of catecholamines on eicosanoid synthesis with special reference to prostanoid/leukotriene ratio. AB - Catecholamines (adrenaline, dopamine, and noradrenaline) stimulate prostanoid synthesis by acting as "cosubstrates." On the other hand, many inhibitors of leukotriene synthesis, such as nordihydroguaiaretic acid and caffeic acid, have a catecholic structure. Catecholamines have opposite effects on prostanoid and leukotriene synthesis in human polymorphonuclear leukocytes and whole blood. Basic phenols (catechol, hydroquinone, and phenol) also increase the prostanoid/leukotriene ratio in polymorphonuclear leukocytes. These actions correlate to their antioxidant capacities and oxidation potentials, and they are not mediated via adrenergic receptors. There is only limited knowledge about the effects of natural catecholamines on the prostanoid/leukotriene ratio in vitro and in vivo. Indirect data suggest that catecholamines could increase prostanoid production in physiological or pathological situations, such as heavy physical exercise, myocardial infarction, and surgical stress. This interaction may also be of clinical importance in asthma, gastric ulcer, and psoriasis, where decreased prostanoid/leukotriene ratios have been reported. PMID- 1459486 TI - Protein A of quinolinate synthetase is the site of oxygen poisoning of pyridine nucleotide coenzyme synthesis in Escherichia coli. AB - De novo biosynthesis of pyridine nucleotide coenzymes in Escherichia coli is initiated by an enzyme complex (quinolinate synthetase) containing protein B which converts L-aspartate into iminoaspartate and protein A, which then generates quinolinate on the pathway to the coenzymes. This complex has been shown to be poisoned by hyperbaric oxygen. We performed assays made dependent on both proteins B and A versus only protein A, using cell-free extracts of hyperbaric-oxygen poisoned and aerobically grown cells. The specific activities were reduced by similar amounts of 68% and 60%, respectively, when measured in assays made dependent on enzymes B and A virus only protein A that was derived from oxygen-poisoned extract. Thus, protein A is the oxygen-sensitive component. PMID- 1459487 TI - Isolation of a malondialdehyde-deoxyguanosine adduct from rat liver DNA. AB - In previous studies, an adduct of malondialdehyde (MDA) with guanine was identified in rat and human urine. Subsequent detection of an adduct with deoxyguanosine (dG) in urine prompted an investigation of its possible occurrence in DNA. Rat liver DNA was hydrolyzed using nuclease P1 and alkaline P-ase and subjected to deoxyribonucleoside analysis using reverse phase high-pressure liquid chromatography (HPLC) with fluorescence detection. A compound was isolated that could not be separated from a synthetic pyrimidinopurine adduct of MDA and dG (dG-MDA). Partial hydrolysis released guanine (Gua), Gua-MDA, and dG in amounts that, in aggregate, were the molar equivalent of the starting material calculated by fluorescence analysis as dG-MDA. Complete acid hydrolysis of the isolate yielded an equimolar amount of MDA. Analysis of liver DNA isolated from growing rats yielded a value for dG-MDA content of 9.0 +/- 1.6 pmol/100 micrograms DNA (mean +/- SEM, N = 5). This value is approximately 7 times those reported for the 8-hydroxy deoxyguanosine content of rat liver nuclear DNA. This study demonstrates that DNA is modified in vivo by reactions of its guanylate moiety with MDA, and indicates that, at least in the case of rat liver DNA, the prevalence of such modifications is greater than those caused by reactions with hydroxyl radicals. PMID- 1459489 TI - Ferritin cannot release iron in vivo if there is no ferritin present. PMID- 1459488 TI - Modification in amino acids of Dead Sea Scroll Parchments. AB - Fragments of Dead Sea Scroll Parchments were extracted for collagen and subjected to amino acid analysis. In modern parchment samples, 90% or more of the protein could be extracted in hot aqueous solution as collagen. In the ancient specimens, 70% or less was extractable. The hot-solution insoluble material was analyzed for collagen. In the soluble extract, the quantity of tyrosine, histidine, and methionine was reduced. Dityrosine was detected. The need to extend such studies is discussed. PMID- 1459490 TI - A chelator is required for microsomal lipid peroxidation following reductive ferritin-iron mobilisation. AB - In the past, antioxidant and chelator studies have implicated a role for iron dependent oxidative damage in tissues subjected to ischaemia followed by reperfusion. As ferritin is a major source of iron in non-muscular organs and therefore a potential source of the iron required for oxygen radical chemistry, we have determined conditions under which ferritin iron reduction leads to the formation of a pool of iron which is capable of catalysing lipid peroxidation. Under anaerobic conditions and in the presence of rat liver microsomes, flavin mononucleotide (FMN) catalysed the reduction of ferritin iron as shown by both continuous spectrophotometric measurements of tris ferrozine-Fe(II) complex formation and post-reaction Fe(II) determination. The presence of either ferrozine or citrate was not found to alter the time course or extent of ferritin reduction. In contrast, the addition of air to the reactants after a 20 min period of anaerobic reduction resulted in peroxidation of the microsome suspension (as determined with the 2-thiobarbituric acid test) only in the presence of a chelator such as citrate, ADP or nitrilotriacetic acid. These results support the concept that reduced ferritin iron can mediate oxidative damage during reperfusion of previously ischaemic tissues, provided that chelating agents such as citrate or ADP are present. PMID- 1459491 TI - Circadian variations in antioxidant defences and lipid peroxidation in the rat heart. AB - Circadian variations in antioxidant defences and lipid peroxidation were investigated in 12 rat hearts perfused during light (i.e., at 08.00, n = 6) and dark cycle (i.e., at 19.00, n = 6). Higher levels of non proteic thiol compounds (P < 0.01), glutathione transferase activity (P < 0.05) and lipid peroxidation (P < 0.01) were detected in evening-excised hearts, associated with a lower (P < 0.05) selenium-dependent glutathione peroxidase activity; superoxide dismutase and glutathione reductase activities, as well as vitamin E content, were similar in the two groups. Moreover, a greater release of thiobarbituric acid reactive substances (P < 0.01) and proteins (P < 0.05) was detected in the myocardial effluent of another group of 5 evening-excised hearts perfused with Krebs Henseleit buffer containing 30 microM cumene hydroperoxide, as compared to 5 light-cycle hearts. In conclusion, a higher oxidative stress seems to be operative in the rat heart during early stages of the dark phase, in spite of the increase level of non proteic thiol compounds (namely, glutathione). An imbalance of antioxidant defences, and/or higher radical generation and unsaturation degree of biomembranes lipids, may be hypothesized to favour myocardial oxidative stress at the beginning of the motor activity phase in rats. PMID- 1459492 TI - Lipoate prevents glucose-induced protein modifications. AB - Nonenzymatic glycation has been found to increase in a variety of proteins in diabetic patients. The present study examined a possibility of preventing glycation and subsequent structural modifications of proteins by alpha-lipoic acid (thioctic acid) as lipoate, a substance which has gained attention as a potential therapeutic agent for diabetes-induced complications. Incubation of bovine serum albumin (BSA) at 2 mg/ml with glucose (500 mM) in a sterile condition at 37 degrees C for seven days caused glycation and structural modifications of BSA observed by SDS-PAGE, near UV absorption, tryptophan and nontryptophan fluorescence, and fluorescence of an extrinsic probe, TNS (6-(p toluidinyl)naphthalene-2-sulfonate). When BSA and glucose were incubated in the presence of lipoate (20 mM), glycation and structural modifications of BSA were significantly prevented. Glycation and inactivation of lysozyme were also prevented by lipoate. These results suggest a potential for the therapeutic use of lipoic acid against diabetes-induced complications. PMID- 1459493 TI - ["Saddam syndrome:" acute psychotic reactions during the Gulf War--renewal of concept of brief reactive psychosis]. AB - 6 patients came to our psychiatric emergency room during the first 2 weeks of the Gulf War presenting the clinical picture of acute delusional paranoid psychosis (4 women and 2 men between the ages of 30-77). 4 were without previously known psychopathology, while the other 2 were known to have had some nonpsychotic cognitive impairment. The first 4 recovered completely within a short time while the other 2 continued to have psychopathological symptoms. We discuss psychogenic or reactive psychosis, and the concept of reactivation when cumulative trauma exceed the individual's personal threshold, as may occur during a war. Different phenomenological syndromes may follow. PMID- 1459494 TI - [Living with celiac disease]. AB - Celiac disease (CD) is caused by ingestion of gluten-containing foods by gluten sensitive individuals. The gluten causes malabsorption by damaging their intestinal mucosa. Adherence to a gluten-free diet is not simple, because the composition of foods stocked on store shelves is often not known, Patients with CD, particularly when adolescent, often refuse to comply with the diet; and parents are occasionally unable, or unwilling, to prepare gluten-free food. Furthermore, school teachers are usually ignorant of the specific dietary requirements of these patients. We examined physical, scholastic, and social aspects of CD patients in comparison with their siblings in the same age groups (10-18 years) to determine whether CD and the need to keep a diet influence these parameters. 25 CD patients and 14 of their siblings were interviewed at home where they filled a questionnaire. The mean adherence to a gluten-free diet was 96.6%; the heights of the patients were comparable to those of their siblings. We did not find significant differences in scholastic achievement and social adjustment between patients and siblings. It appears that children and adolescents with CD can live with their disease and keep a gluten-free diet while performing satisfactorily in school. However, some complained of difficulties, such as feeling uneasy at social gatherings, wanting to discuss their disability with friends, and feeling unhappy. Some were angry at society for pitying them and considering them as having a disease, while the patients considered themselves as having a food sensitivity. PMID- 1459495 TI - [Cytokines in anorexia nervosa--nutritional or neuroimmunal changes?]. AB - Natural cell-mediated cytotoxicity (CMC), spontaneous release of tumor necrosis factor (TNF-alpha) by mononuclear cells in vitro, and PHA-induced interferon (IFN gamma) production were examined by standard methods in 14 females with anorexia nervosa (AN) and marked weight loss and in 16 normal matched controls. The results were confirmed by neutralization with monoclonal antibodies. In the anorectic patients there was a significant increase in TNF production (16 +/- 5 vs 4 +/- 3 mu/ml), and depressed CMC (4 +/- 2 vs 10 +/- 3 lytic units per 50/10(6) cells) and IFN-gamma production (172.5 +/- 25 vs 367 +/- 34 mu/ml). Following successful refeeding and nutritional rehabilitation, all values returned to normal. Thus there are changes in cytokines and defective natural cytotoxicity in AN, apparently related to undernutrition and not to neuroimmunomodulation. The increased TNF-release may further suppress food intake and enhance tissue catabolism, suggesting that nutritional rehabilitation should be the earliest therapeutic goal in anorexia nervosa. PMID- 1459496 TI - [The day-care unit as a framework for successful community rehabilitation]. AB - Due to rapid advances in psychiatric treatment, increased sophistication of welfare services, and increasing life expectancy, the number of psychiatric patients is increasing rapidly. Many of them do not have the necessary adaptive capacity to deal satisfactorily with their daily functions, such as housework, financial arrangements, and medical treatment. These patients could be assisted in day-care treatment units. We present the ideology and the different models of psychiatric day-care units which are becoming widely used in treatment, especially for rehabilitation of chronic mental patients. PMID- 1459497 TI - [Lithium augmentation for mianserin-resistant depression in the elderly]. AB - Depression in the elderly is characterized by a prolonged course and resistance to pharmacological treatment. Moreover, in old age sensitivity to the anticholinergic and cardiac side-effects of tricyclic antidepressants (TCA) increases. Recently new antidepressants with fewer side-effects have been developed. Of these, trazodone and mianserin have been particularly recommended for the treatment of depression in older patients. However, the effects of these new compounds on depression are similar to those of the older TCA's, leaving a substantial number of elderly patients with resistant depression. While there are many publications on the potentiation of the effect of TCA's by lithium carbonate, there is little data on the potentiation of the effects of trazodone and of mianserin by lithium, and no reports of their combined use in elderly patients. Birkhimer et al. reported a case of successful treatment of refractory depression with trazodone and lithium in a 45-year-old man. Heninger et al. successfully treated 2 treatment-refractory patients (aged 52 and 58 years, respectively) with a combination of mianserin and lithium. Price et al. reported that 85% of 12 drug-resistant patients improved when treated with lithium and mianserin, but only 22% of 9 patients treated with lithium and trazodone. We report a 73-year-old man with resistant depression whose physical condition contraindicated tricyclic antidepressants, in whom the combination of mianserin and lithium was both safe and effective. PMID- 1459498 TI - [Combined tricyclic antidepressants and ritalin in elderly depressives]. AB - Psychostimulants, including ritalin (methylphenidate), were used as antidepressives in the '50s but were then replaced by tricyclics and MAO inhibitors. Treatment of depression with psychostimulants is still controversial. Several anecdotal reports in the past decade approved the use of tricyclic antidepressants (TCA) together with methylphenidate in apathetic and withdrawal states in medically ill and in elderly patients. Ritalin elevates mood by releasing catecholamines and blocking their re-uptake, and also increases serum TCA levels. 5 men and 5 women between the ages of 65 and 79 were diagnosed as suffering from major depressive disorders, either single or recurrent, based on the Revised Diagnostic and Statistical Manual for Mental Disorders (DSM-III-R). They had been treated with TCA for up to several months with no response. Following addition of methylphenidate, 5-15 mg/d for 2 weeks, 4 men and 3 women improved rapidly, 2 of them within 24 hours. PMID- 1459499 TI - [Withdrawal reactions after clomipramine]. AB - Abrupt or gradual discontinuation of tricyclic antidepressants may precipitate withdrawal symptoms. The most common of these are general somatic or gastrointestinal distress, anxiety and agitation, sleep disturbance, akathisia, parkinsonism, paradoxical behavioral activation and mania. There are very few reports of withdrawal reactions following discontinuation of clomipramine since it has not been in use in the US until recently. 2 patients with withdrawal symptoms following discontinuation of clomipramine are presented. A 45-year-old man had general somatic symptoms, including headache, myalgia, weakness, fatigue (flu-like syndrome) and nervousness and insomnia after clomipramine, 75 mg/d, had been discontinued abruptly. All symptoms disappeared without treatment after 3 days. A 47-year-old woman presented mainly with severe insomnia, anxiety, agitation, jitteriness and tension after discontinuing a low dose of 25 mg/d of clomipramine. Symptoms disappeared after she started self-treatment with 50 mg/d of the drug. It is important to differentiate withdrawal symptoms from relapse of the primary psychiatric disorder. PMID- 1459500 TI - [Subclinical renal involvement in rheumatoid arthritis]. AB - No evidence of renal involvement was found in 104 patients with rheumatoid arthritis in routine laboratory tests, including serum creatinine, urea, uric acid, sodium, potassium, calcium, phosphorus, and urinalysis. In view of recent publications (1-9) which report renal involvement in rheumatoid arthritis, we studied 16 patients of our group (nonrandomized, 3 men and 16 women, average age 55.4 years, average duration of disease 11.9 years). We examined creatinine clearance, urinary excretion of alpha-2 microalbumin, beta-2 microglobulin, cystine, and urine concentration and acidity after a 10-hour fast. 10 patients had disturbances in 1 or more of the functions examined, in 9 of whom tubular functions were involved. In 6 there was no evidence of renal involvement. There was no correlation between renal involvement and past or present therapy, but there were direct correlations between renal involvement, duration of disease and age. Thus we found evidence for subclinical renal damage not revealed by routine laboratory tests in patients with rheumatoid arthritis. This damage should be taken into consideration when operation, examination with contrast material, or treatment with other nephrotoxic agents are being considered in these patients. PMID- 1459501 TI - [Poststreptococcal reactive arthritis]. AB - Reactive arthritis is defined as arthritis of 1 or more joints, in association with infection at a distant site, but without the infective agent being found in the synovial fluid. Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever, have been classified as having poststreptococcal reactive arthritis. We describe 6 patients seen during the winter of 1991 who had various clinical presentations of poststreptococcal reactive arthritis. This condition is considered by some as a distinct disease, but by others as part of the spectrum of acute rheumatic fever. PMID- 1459502 TI - [Brucella infection of the testis mimicking malignancy]. AB - A testicular mass is a diagnostic challenge, as it may include both benign and malignant processes. Due to the difficulty in diagnosis and the need to prevent complications, it is sometimes necessary to perform orchiectomy. We present an unusual case of brucellosis in which the presenting features were persistent cough for 6 months and a right testicular mass. The clinical picture and ultrasound findings suggested malignancy. Orchiectomy and medical treatment resulted in rapid resolution of symptoms. PMID- 1459503 TI - [Sweet's syndrome in a young woman]. AB - Sweet's syndrome is an uncommon and dramatic skin disease associated with systemic symptoms such as fever, headache and arthralgia. Since it is also accompanied by an increased erythrocyte sedimentation rate and leukocytosis, it may be confused with severe systemic infections and other systemic illnesses. We describe a 30-year-old woman who presented with typical features of the disease. They included high fever, headache, sore throat, increased sedimentation rate, and a painful violaceous, nodular and papular rash on her limbs and upper trunk. Histologic features included dense neutrophilic infiltration and edema of the dermis, with foci of leukocytoclasia, but without leukocytoclastic vasculitis. There was a dramatic repose to treatment with prednisone. PMID- 1459504 TI - [Organization of psychiatric services in Israel and their financing]. PMID- 1459505 TI - [Psychosurgery in the modern era: therapeutic and ethical aspects]. PMID- 1459506 TI - [Musical hallucinations and psychopathology]. PMID- 1459507 TI - [Sleep disturbances in children and adolescents]. PMID- 1459508 TI - [Serological diagnosis of celiac disease]. PMID- 1459509 TI - [Tegretol as a therapeutic agent for psychotic disorders]. PMID- 1459510 TI - [The Human Genome Project: ethical and social implications]. PMID- 1459511 TI - [Selling of mental health services: some ethical doubts]. PMID- 1459512 TI - [The status of the fetus in Halacha]. PMID- 1459513 TI - [Living with celiac disease]. PMID- 1459514 TI - [Is there a need for drug therapy in childhood febrile seizures?]. PMID- 1459515 TI - Mitochondrial dysfunction in the non-obstructed lobe of rat liver after selective biliary obstruction. AB - In order to elucidate the function of non-obstructed hepatic lobe during partial cholestasis, we have examined the effects of selective biliary obstruction on the mitochondrial energy transducing system in rat liver. The non-ligated lobe became hypertrophic after ligation of the bile ducts that drained 90% of the liver, and there was no increase in the level of serum bilirubin, alkaline phosphatase activity, or bile acids. However, mitochondrial oxidative phosphorylation function, specific enzymic activities of the oxidative phosphorylation complexes, and the subunit contents of these complexes were markedly decreased in the non obstructed lobe at 4 weeks after the 90% biliary obstruction. There was no increase in the specific content of mitochondrial DNA. The mitochondrial energy transducing system in the non-obstructed lobes is not enhanced, but is significantly impaired during prolonged selective biliary obstruction, despite normal serum biochemical data and hypertrophy of the non-ligated lobe. These results imply early release of obstruction of cholestatic lobe, e.g. by biliary drainage, would be beneficial for maintaining the mitochondrial function in the non-cholestatic lobe. PMID- 1459516 TI - Octylonium bromide in the treatment of the irritable bowel syndrome: a clinical functional study. AB - We investigated the effect of octylonium bromide on a number of symptoms and functional aspects of the irritable bowel syndrome. Seventy-two patients complaining mainly of abdominal pain were studied in a double-blind trial (octylonium bromide 40 mg tid for 4 weeks or placebo). Clinical parameters were: abdominal pain, bloating and bowel frequency. Sigmoid manometry with simultaneous recording of the thresholds for distension and/or pain upon graded inflation of an endoluminal balloon was performed before and at the end of treatment. In contrast to placebo, octylonium bromide significantly reduced pain and bloating, and significantly increased (p < 0.02) the pain threshold throughout the treatment period. However, comparison with the placebo group failed to show any relevant differences. Neither treatment influenced the frequency of bowel movement. Sigmoid motility during distension was significantly reduced after octylonium bromide (p < 0.05), but it did not change after placebo. In conclusion, octylonium bromide is capable of reducing symptoms and motor reactivity of the sigmoid in patients with irritable bowel syndrome. PMID- 1459517 TI - Predictors of relapse in peptic ulcer. AB - Four hundred and two patients with peptic ulcer were selected for acute therapy with either pirenzepine (100 mg/day) or cimetidine (800 mg/day) using the envelope method. Those who achieved healing within 3 months (251 patients) were randomized in a double-blind fashion to maintenance therapy with either pirenzepine (75 mg/day) or placebo. In a preliminary study of 163 patients in which a multiple regression life-table method was employed, 4 out of 15 possible predictors were found to have a significant influence on relapse. These were site of ulcer lesions, psychological stress, endoscopic findings at the time of healing of the original ulcers, and acute therapy. Stratified analysis of the evolution of relapse by the Cutler-Ederer life-table method indicated that several other factors also influenced relapse in certain patient subgroups. Most relapses (93.8%) occurred at the same site as, or close to the site of, the original ulcers, indicating that ulcer scars also play a role in relapse. PMID- 1459518 TI - Early cancer of the gastric remnant--with special emphasis on the importance of follow-up of gastrectomized patients. AB - Seven patients with early cancer of the gastric remnant (group 1) and nine with gastric remnant cancer which developed after surgery for early gastric cancer (group 2), were studied clinicopathologically. The findings can be summarized as follows: In group 1, the majority of cases were classified as type I by gross type. Most lesions were in the posterior wall of the remnant stomach. All lesions were differentiated carcinomas. In group 2, of the nine early gastric tumors resected at the initial surgery, six were present at site A and three at site M. The gross type of the tumor was varied. Six patients underwent a Billroth II, and two a Billroth I, resection. The findings at the second operation (for gastric remnant cancer) showed that five lesions were located in the gastric stump or anastomosed region and four in the posterior or anterior wall of the remnant stomach. Histologically, the lesions included four undifferentiated and five differentiated carcinomas. Of the nine lesions involving the gastric remnant, only two were at an early stage, the remaining seven being at an advanced stage. The outcome was extremely poor in this group. Many of the patients died of carcinomatous peritonitis. In summary, a large percentage of the patients of group 1 had a type I lesion in the remnant stomach. In group 2, more than half of the lesions were located in the gastric stump or at the site of the anastomosis, and the majority of the lesions were at an advanced stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459519 TI - Results of orthotopic liver transplantation: a personal experience. AB - The authors report on their experience of 158 liver transplants performed on 135 patients. Nineteen underwent re-transplantation and four of these required a second re-transplantation; total number of re-transplantations: 23 (14.6%). Hepatic cirrhosis was the most common indication (50.6%), of which alcoholic cirrhosis was the most common type (32.5%). The authors briefly report on their operative techniques and the results of their procedures. The operative mortality (30 days) was 13.3% (18 out of 135 patients). Complications included nine cases of hepatic artery thrombosis (5.7%), four of arterial stenosis (2.5%), one case of portal venous stenosis (0.63%), four cases of post-operative portal venous thrombosis (2.5%), seven of biliary fistula (4.4%; five following choledochocholedochostomy and two following choledochojejunostomy), and two cases of common bile duct stenosis (1.3%). The actuarial survival rate at 48 months is 80%. PMID- 1459520 TI - TRH-immunoreactivity in chronic pancreatitis. AB - Thyrotropin-releasing hormone (TRH) is abundantly present in the pancreas. We studied the circulating TRH-immunoreactivity (IR) in 27 patients with chronic pancreatitis (CP) and different degrees of exocrine pancreatic insufficiency (EPI), as well as in 23 normal subjects. Furthermore we examined the effect of oral administration of 100 g glucose on peripheral TRH-IR in normal subjects (n = 5) and in patients with severe exocrine insufficiency (SEI, n = 5). Basal TRH-IR plasma levels in the CP group (20.8 +/- 7 fmol/ml, mean +/- SD) were significantly lower (p < 0.005) as compared with the normal subjects (38 +/- 14). TRH-IR plasma levels in patients with CP and SEI (15.8 +/- 3) were significantly lower (p < 0.05) than in patients with normal pancreatic function (28.1 +/- 8), but were no different from those in patients with CP and moderate exocrine insufficiency (18.7 +/- 5). In normal controls TRH-IR rose 120-180 min after glucose ingestion from 33 +/- 5 to 64 +/- 20 fmol/ml, while no increase in TRH-IR levels was observed in patients with SEI. We conclude that circulating TRH-IR levels are mainly of pancreatic origin. Patients with SEI have very low peripheral TRH-IR, indicating that CP does indeed influence TRH-release. PMID- 1459521 TI - Surgical management of biliary cystadenocarcinoma. AB - Four patients, one woman and three men, with biliary cystadenocarcinoma were surgically treated during a 7-year period. The mean age was 58 years. Symptoms prior to admission were mild, and blood tests including liver function tests, CEA and AFP were for the most part within the normal range. Surgery followed diagnostic work-up including US, ERCP, CT, angiography and MRI. Radical surgery was accomplished in three patients by extended left lobectomy in two and extended right lobectomy in one patient, respectively, in this latter patient preceded by therapeutic embolization of the right portal branch prior to resection, while the fourth patient had a palliative resection. Histological examination revealed papillary adenocarcinoma with mucin production within the cyst. The size of the cyst (maximum diameter) varied between 4.5 and 24 (mean 12) cm. The postoperative course was uneventful in all patients. Two patients are alive with no sign of recurrence 5 and 53 months after surgery, while two patients died after 26 and 75 months, respectively. Thus, radical resection of this rare kind of malignant hepatic tumor seems to offer a chance of long-time survival. PMID- 1459522 TI - Morbidity and mortality after abdominal operations for cancer. AB - A review of 316 consecutive patients operated on for intra-abdominal cancer was undertaken to analyze the incidence of postoperative morbidity and mortality and identify contributory factors. The overall postoperative morbidity and mortality after operations performed for primary cancer were, respectively, 26% (75/288) and 7% (20/288), and those seen after operations for recurrent cancer 43% (12/28) and 29% (8/28). Factors that were statistically associated with a fatal outcome were recurrent cancer (p = 0.0005), palliative resection (p = 0.005), a serum albumin level under 35 G/L (p = 0.011) and a weight loss of more than 5 kilograms (p = 0.046); those associated with a significantly greater complication rate were a serum albumin level under 35 G/L (p = 0.000004), a weight loss of more than 5 kilograms (p = 0.00007), intra-abdominal carcinosis (p = 0.0057), and an emergency procedure (p = 0.048). Infective complications were more common among the patients who underwent resective surgery than among those operated on non resectively. It is concluded that preoperative malnutrition is predictive of both postoperative complications and increased mortality, and that recurrent disease and palliative surgery are associated with high postoperative mortality. PMID- 1459523 TI - Prophylactic effect of albendazole in experimental peritoneal hydatidosis. AB - To determine the effectiveness of prophylactic short-term administration of albendazole in experimental peritoneal hydatidosis this substance was given at a dose of 15 mg/kg for 96 hours prior to scolex implantation. In contrast to the 81.8% of the controls, only 11.1% of the experimental animals developed intraperitoneal hydatidosis over a period of 18 weeks (p < 0.001). The newly defined cyst index was also decreased from 2.09 to 0.22 by the administration of albendazole (p < 0.005). It is concluded that albendazole, when given for 96 hours prior to any suspected intraperitoneal spillage of viable hydatid cyst contents could significantly reduce secondary peritoneal hydatidosis. PMID- 1459524 TI - Portal vein thrombosis following sclerotherapy. AB - We present the case of a woman with idiopathic portal hypertension who underwent sclerotherapy for bleeding esophageal varices. She had a rebleed 27 months after complete eradication of esophageal varices. Endoscopy showed bleeding gastric varices. Ultrasonography, and later splenoportography, revealed a large thrombus in the right branch of the portal vein causing gross dilation of the portal and splenic vein. A proximal splenorenal shunt was done to decompress the portal system and hence gastric varices. Repeat endoscopy 4 weeks after surgery revealed complete disappearance of the gastric varices, while ultrasonography at 38 weeks showed marked decompression of the portal system with complete disappearance of the thrombus from the right branch of the portal vein. No new thrombus formation was seen. PMID- 1459525 TI - Treatment of locoregional recurrence after intentional curative resection of pancreatic cancer. AB - In order to analyze the results of treatment of patients with locoregional recurrence after intentional curative resection of pancreatic cancer, a retrospective study was performed. During the period 1978-1988, 108 patients underwent an intentional curative resection fo the pancreas. In 34 patients locoregional recurrence occurred, all within a period of three years (cumulative recurrence rate 56%). Sixty-eight percent of the patients presented with upper abdominal pain, and 62% with weight loss. Survival was significantly better (p = 0.02) in the group of 18 patients without distant metastases (1-year survival 22%) than in the 16 patients with distant metastases (1-year survival 0%). Five patients without proven distant metastases were treated by resection or chemotherapy. The mean survival was 33 months (range 6-74) in the treated group, and 4 months (0.4-7 months) in the untreated group, p = 0.002. In this retrospective study the longest survival was seen after radical resection of locoregional tumor recurrence. We therefore recommend that patients with locoregional recurrence without distant metastases after intentional curative resection of pancreatic cancer be treated. PMID- 1459526 TI - Review of operative indication and prognosis in gastric cancer with hepatic cirrhosis. AB - Prognosis following surgery for gastric cancer has markedly improved as a result of early diagnosis, advances in operative techniques, and perioperative management. However, gastrointestinal surgery in patients with hepatic cirrhosis has continued to be associated with a high operative morbidity and mortality. On the basis of a detailed classification of the preoperative hepatic conditions into three risk groups, we have established a preoperative means of assessing surgical indication. Depending on the preoperative assessment, 40 gastric cancer patients with hepatic cirrhosis underwent surgical exploration. Thirty-seven patients (92.5%) received gastric resection, while 3 patients (7.5%) were non resectable. Postoperative complications occurred in only 8 patients (20%), and no anastomotic leakage occurred; the overall operative mortality was zero. The five year-survival rate following a curative resection, as calculated by Kaplan-Meier statistical analysis, was 51.4% (n = 30). PMID- 1459527 TI - The risk of cholecystectomy for acute cholecystitis in diabetic patients. AB - In order to evaluate the risk of acute cholecystitis in diabetic patients, we analyzed 2,700 consecutive cholecystectomies, 566 of which were performed in the presence of acute cholecystitis. Of these patients 123 had diabetes mellitus (DM) and 433 had no diabetes (ND). The aim of this study was to establish the comparative risks in the two groups. We found that diabetics are more likely to be operated on in the acute stage of their disease (22% vs. 12%). The DM group had a higher rate of septic bile, gangrenous changes and perforations of the gallbladder wall. The morbidity rate was higher in the DM group (21% vs. 9%), and mortality was slightly higher in the DM group. The degree of additional operative risk does not in our view justify recommending cholecystectomy in diabetic patients with asymptomatic gallstones. Early surgery however, is highly recommended in diabetics with symptomatic gallstones and acute cholecystitis. PMID- 1459528 TI - Results of transhiatal esophagectomy in cancer of the esophagus and other diseases. AB - We present the results we obtained during the last 12 years with transhiatal esophagectomy. Two hundred and eighty-three patients were operated on using this procedure; 171 of them underwent the operation for cancer of the esophagus, 73 for cancer of the cardia, and 11 for cancer of the hypopharynx. The tumor stage, the operative technique, and the type of esophageal replacement (stomach: 62.9%; colon: 37.1%) are described. Overall operative mortality was 5.6%, mainly as a result of respiratory insufficiency. Long-term survival was 11.9% at five years for cancer of the esophagus, much lower than the 48.3% for cancer of the cardia. PMID- 1459529 TI - Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels. AB - The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma samples of patients with cirrhosis and chronic hepatic encephalopathy, taking part in a 3-month randomized, double-blind trial. Twenty-five patients had received 0.24g of BCAA per kg body weight, 24 had received an equinitrogenous amount of casein, in addition to a diet providing 0.7-1.0 g/kg of protein. Thirty-eight were males, 11 post-menopausal women. Fasting prolactin did not show any change in the BCAA group, where mental state significantly improved. In the casein group plasma prolactin increased by nearly 50% during the 3-month period. Similarly, estradiol concentrations were unchanged during BCAA supplementation, and increased during casein treatment. The analysis of variance demonstrated significant differences between the 2 treatments. Liver function tests and nutritional parameters (albumin, transferrin, urinary creatinine) supported a superiority of BCAA over casein. These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission, but are due mainly to maintained liver function, possibly related to improved nutrition. PMID- 1459530 TI - Management of pancreatic injuries. AB - With the aim of aiding the accurate diagnosis and treatment of patients with pancreatic injuries, we reviewed the medical records of all those patients, treated for traumatic pancreatic lesions at our hospital in the period between 1971 and 1987. For all twenty-four male patients the mechanism of the injury, the diagnostic methods employed, associated injuries, location of the pancreatic injury, the presence of pancreatic duct lesion, treatment, the final outcome, and complications are described. In our view, the high mortality rate of patients with pancreatic trauma is due not to the pancreatic injury per se, but to the severe concomitant injuries resulting from a high-energy trauma. On the basis of the literature and our own experience we designed a flow chart for the management of pancreatic injuries. If the history and physical examination indicate that intra-abdominal injury might be present, radiographic and ultrasound investigation are the diagnostic methods of choice. Patients without pancreatic duct injury can be treated with debridement and external suction drainage. If pancreatic duct lesion is presented and is located to the right of the superior mesenteric vessels, treatment should consist of partial pancreatic resection and pancreatico-jejunostomy or a Whipple procedure. If the pancreatic duct lesion is located to the left of the superior mesenteric vessels, distal pancreatectomy and splenectomy with pancreatico-jejunostomy, should be performed. PMID- 1459531 TI - Influence of beta blockade on branched chain amino acid concentrations in cirrhosis. AB - Cirrhosis of the liver is typically accompanied by low plasma levels of the three branched chain amino acids (BCAA). These patients also demonstrate increased concentrations of several hormones such as insulin, glucagon and catecholamines. Catecholamines have been shown to influence the plasma levels of amino acids in healthy subjects and diabetics. In the present study, amino acid concentrations were investigated before and up to 3 hours after beta blockade (Inderal, 40-80 mg, n = 10) or fasting (n = 8) in cirrhotic patients. In the basal state the patients had low levels of all three BCAA, as compared with healthy subjects. Norepinephrine was more than 3 times as high in the patients (3.65 +/- 0.6 vs. 0.84 +/- 0.08 nmol/l, p < 0.01) while epinephrine was only slightly raised (0.43 +/- 0.1 vs. 0.25 +/- 0.06 nmol/l, NS). Significant correlations were observed between the concentrations of norepinephrine and individual as well as the sum of the three BCAA (r = 0.43-0.62, p < 0.05-0.001), while no correlation was observed between the BCAAs and epinephrine or insulin. Three hours after beta blockade the concentrations of leucine (basal: 74 +/- 6, 180 min: 89 +/- 6 mumol/l, p < 0.05) and valine (basal: 110 +/- 10, 180 min: 132 +/- 11 mumol/l, p < 0.01) had increased significantly. A similar tendency was observed for isoleucine. No changes were observed after prolonged fasting. The results suggest that catecholamines, primarily norepinephrine, might contribute to the low levels of BCAA in cirrhotics. PMID- 1459532 TI - Differential diagnosis of space-occupying lesions of the liver with MR imaging. AB - In a retrospective study of 84 patients who underwent MRI examination of the liver the qualitative parameters margin, shape, internal structure, signal intensity and the presence of a capsule were evaluated in 152 lesions comprising 48 hemangiomas, 54 secondary deposits, 23 hepatomas, 8 simple cysts, 17 hydatid cysts, 1 abscess and 1 focal fatty infiltration. Our main objective was to differentiate hemangiomas from secondary deposits and hepatomas. In hemangiomas the combination of smooth margin (98%) round or oval shape (90%) homogeneity (96%) very high signal intensity on T2-weighted sequence (94%), and the complete absence of capsule helped to distinguish them from secondary deposits and hepatomas in the majority of cases. It is concluded that with MR imaging we can establish the diagnosis of focal lesions of the liver in about 95% of cases. PMID- 1459533 TI - Relationship of cholecystectomy and detachment of the common bile duct to chronic bile duct dilation. AB - A combination of a cholecystectomy and detachment of the supportive tissue surrounding the extrahepatic bile duct results in chronic bile duct dilation. To clarify whether this cholangiectasis is due to the detachment of the surrounding tissue or to the cholecystectomy, we have studied 4 groups of adult mongrel dogs, i.e., a control group given a sham operation (n = 20), a group given cholecystectomy (n = 20), a group that had the surrounding tissue detached from the bile duct (n = 20), and a group given both a cholecystectomy and detachment of the surrounding tissue (n = 29). On examination by cholangiography at 1, 2, 3, and 4 weeks after the initial laparotomy, no significant cholangiectasis was found in dogs subjected to either cholecystectomy alone or to detachment of the surrounding tissue alone. In contrast, in dogs subjected to a cholecystectomy combined with detachment of the bile duct, the bile duct gradually dilated, resulting in significant cholangiectasis at 4 weeks. However, the intrabiliary pressure, the residual pressure, and the actual resistance value, which are indices of a passage disturbance in the sphincter of Oddi, were normal in all 4 groups. It is therefore concluded that both the extirpation of the gallbladder, and the lack of supportive tissue surrounding the bile duct were responsible for the resulting cholangiectasis. PMID- 1459534 TI - Extended excision of the ampulla of Vater--a new operative technique for elderly patients. AB - This report describes a 72-year-old female patient treated by extended excision of recurrent ampullary carcinoma. The procedure comprised pylorus-preserving resection of the descending segment of the duodenum, and excision of a large portion of the pancreatic head using an ultrasonic surgical dissector. Restoration of food transit, pancreatico-jejunal and choledocho-jejunal anastomosis by a Roux-en-Y reconstruction was readily accomplished. The operation, which has the advantage of being more radical and accurate than the standard excision of the ampulla of Vater, and less time-consuming and mutilating than the Whipple procedure, may be indicated in elderly patients with ampullary carcinoma. PMID- 1459535 TI - Ectopic ACTH-producing adenocarcinoma of the stomach. AB - A 73-year-old female was admitted to our hospital because of weight loss and pretibial edema. Plasma levels of adenocorticotropic hormone (ACTH) and cortisol were elevated, and neither hormone showed circadian rhythm. Dexamethasone (2 mg for 2 days) failed to reduce the urinary excretion of 17-hydroxycorticosteroids and the plasma cortisol level. The stomach biopsy specimens showed a moderately differentiated papillo-tubular adenocarcinoma. Computed tomography of the abdomen showed multiple metastases to the liver. Immunohistochemical staining of the autopsy specimens showed immunoreactive ACTH in the primary tumor cells of the stomach as well as the metastatic tumor cells of the liver. On the basis of the clinical, histological and immunohistochemical findings, we diagnosed this patient as having ectopic ACTH syndrome caused by adenocarcinoma of the stomach. PMID- 1459536 TI - Providing mental health care for children and adolescents. PMID- 1459537 TI - Capitation from a provider's perspective. PMID- 1459538 TI - Disease-prone and self-healing personalities. PMID- 1459539 TI - Rehabilitation and quality of life. PMID- 1459540 TI - Chronic dyspnea and suicide in elderly men. AB - In a structured psychological autopsy study of suicide in older adults, 14 cases in which the subjects experienced chronic dyspnea in the months or weeks before death were examined. Thirteen of the subjects were white men. Most had a diagnosable psychiatric disorder, although none had previous contact with a mental health professional. Other common characteristics were chronic or terminal heart or lung disease, very recent contact with a primary physician, prior experience of self or a significant other suffering a debilitating disease, and a fiercely independent and inflexible personality type. The cases illustrate the intricacy of risk factors associated with suicide and alert other investigators and health care professionals to a possible link between chronic dyspnea and suicide risk. PMID- 1459541 TI - Religious affiliation and major depression. AB - Data from the Duke Epidemiologic Catchment Area survey were used to examine the relationship between religious affiliation and major depression among 2,850 adults in the community. Religious affiliations were categorized into six groups: mainline Protestant (27 percent), conservative Protestant (59 percent), Pentecostal (4.2 percent), Catholic (2.4 percent), other religions (2.6 percent), and no affiliation (4.4 percent). The six-month prevalence of major depression among Pentecostals was 5.4 percent, compared with 1.7 percent for the entire sample. Even after psychosocial factors such as gender, age, race, socioeconomic status, negative life events, and social support were controlled for, the likelihood of major depression among Pentecostals was three times greater than among persons with other affiliations. Carefully designed studies are needed to understand the complex interactions of religion and mental health. PMID- 1459542 TI - Perspectives on effective advocacy for homeless mentally ill persons. AB - To make appropriate treatment and public policy recommendations to address the problems of homeless mentally ill persons, it is important to differentiate the homeless mentally ill population from the homeless population in general. Effective advocacy for homeless mentally ill persons should have realistic goals that address the specific needs of that population rather than attempt to change the basic problems of society. The effective advocacy that has secured services for developmentally disabled persons can serve as a model. Mental health professionals' limited response to the problems of homeless mentally ill persons has further stigmatized mentally ill persons in general; one of the most powerful actions mental health professionals could take to fight stigma would be to help provide treatment and residential alternatives for homeless mentally ill persons. The recommendations of both the first and the second American Psychiatric Association task forces on the homeless mentally ill are discussed. PMID- 1459543 TI - Ethical issues for academic participants in state-university collaboration programs. AB - State-university collaboration programs often create ethical dilemmas for participants because of their conflicting values, goals, and expectations. Treatment and administrative staff in state agencies often seek to create an atmosphere of managed stability rather than fostering patients' autonomy. Academic participants in collaboration programs often feel impelled to change the system, even though the goal of collaboration requires them to find common ground with state agency staff. Academic participants must decide whether collaboration programs will contribute to needed reforms without overly compromising professional and academic standards. If they cannot endorse the values and quality of care provided in state systems, they must consider whether their participation should be conditioned on an agreement to work toward change. However, even in situations that are improving, clinicians must not let temporary compromises become permanent. PMID- 1459544 TI - Patterns of utilization of outpatient mental health services by children and adolescents. AB - Although as many as one-fifth of children and adolescents may meet DSM-III criteria for at least one psychiatric diagnosis, data from the Minnesota Department of Human Services for 1988 show that only 20 to 38 percent of children and adolescents in the state who are eligible for medical assistance and who are potentially in need of psychiatric care are referred for or seek treatment. A study of publicly funded mental health care for youths under 18 found that in 1988 the average cost for state-supported psychiatric services per outpatient case was $520, compared with $8,556 per inpatient case. However, overall cost of state-supported mental health services for youths under 18 increased by 28 percent between 1987 and 1988, primarily due to increases in payments for inpatient care of patients with dual diagnoses of mental illness and chemical dependency. PMID- 1459545 TI - Indicators of adverse somatic outcome in three Veterans Affairs nursing homes. AB - Frequencies of undernutrition, bedsores, and deterioration in activities of daily living were compared in three Veterans Affairs nursing homes serving both chronic psychiatric patients and medical or neurological patients. The three facilities varied in the proportions of patients with adverse outcomes, with one home having noticeably higher rates for both subgroups of patients. In each home, the two subgroups were equally likely to show evidence of adverse outcome, suggesting that differences in the frequency of adverse outcomes among the facilities were accounted for by extrinsic factors related to quality of care rather than intrinsic factors related to patient characteristics. PMID- 1459546 TI - The economic burden of mental illness. AB - Mental illness imposes a substantial burden on individuals and society. Using data from national surveys and a newly developed methodology for calculating costs, the authors estimate that in 1985 the total economic costs of mental illness were $103.7 billion. Of this total, direct treatment and support costs were $42.5 billion, or 11.5 percent of total personal health care spending for all illnesses. Morbidity costs--the value of reduced or lost productivity- amounted to $47.4 billion. Mortality costs--the lost value of productivity due to premature death resulting from mental illness--were estimated to be $9.3 billion, or 5.1 percent of total productivity losses for all deaths. Other related costs, including the cost of caregiver services, amounted to $4.5 billion. PMID- 1459547 TI - Predicting need for long-term hospitalization of severely mentally ill young adults. PMID- 1459548 TI - Multiple personality disorder presenting as postpartum depression. PMID- 1459549 TI - Psychotropic medications. PMID- 1459550 TI - Methadone and cocaine. PMID- 1459551 TI - Cost of HIV. PMID- 1459552 TI - Data watch. A snapshot look at hospital staffing reforms. PMID- 1459553 TI - RBRVS impact. Academic medical centers gauge impact of new fee schedule. PMID- 1459554 TI - Stories of survival. Riots in Los Angeles. Being prepared: a lesson well-learned for area facilities. PMID- 1459555 TI - Stories of survival. Hurricane Andrew. South Florida hospitals shared resources and energy to cope with the storm's devastation. PMID- 1459556 TI - Experts agree on this: it was a banner year for health care polls. PMID- 1459557 TI - Four experts look at technology under Clinton-style reform. Interview by Kevin Lumsdon. PMID- 1459558 TI - The year's most quotable quotes: what the health care leaders said. PMID- 1459559 TI - On-the-job training vital supplement to degree. PMID- 1459560 TI - Inching toward EDI: experts look at obstacles. PMID- 1459561 TI - CONs come back in context of state reform plans. American Hospital Association, State Issue Forum. PMID- 1459562 TI - DVA to study financial impact of home care. PMID- 1459563 TI - Health care reform issues call for plain talk. AB - Getting the health care reform message out to your community is vital, writes the author, but learning how to communicate that message is equally critical. To do that, he says, you must know your audience, establish common ground with as many people as possible, and say what you have to say in language they can understand. The media filter, he says, poses a persistent challenge to communicating the issue. PMID- 1459564 TI - Graphical displays: implications for divided attention, focused attention, and problem solving. AB - When completing tasks in complex, dynamic domains observers must consider the relationships among many variables (e.g., integrated tasks) as well as the values of individual variables (e.g., focused tasks). A critical issue in display design is whether or not a single display format can achieve the dual design goals of supporting performance at both types of tasks. We consider this issue from a variety of perspectives. One relevant perspective is the basic research on attention and object perception, which concentrates on the interaction between visual features and processing capabilities. The principles of configurality are discussed, with the conclusion that they support the possibility of achieving the dual design goals. These considerations are necessary but not sufficient for effective display design. Graphic displays map information from a domain into visual features; the tasks to be completed are defined in terms of the domain, not in terms of the visual features alone. The implications of this subtle but extremely important difference are discussed. The laboratory research investigating alternative display formats is reviewed. Much like the attention literature, the results do not rule out the possibility that the dual design goals can be achieved. PMID- 1459565 TI - Choosing specifiers: an evaluation of the basic tasks model of graphical perception. AB - Effect sizes obtained from 39 experiments were used to evaluate the predictions of the basic tasks model of graphical efficacy. This model predicts that performance will be attenuated with graphical displays as a function of the particular specifier, or visual dimension, used to code data values. In this review the basic tasks model predicted performance more accurately than did Tufte's data-ink principle. In addition, variability in effect sizes across studies revealed that the model was more successful at predicting performance in local (focusing) tasks than in global information synthesis tasks. Furthermore, the model was better at predicting performance in tasks requiring the use of physically present rather than remembered graphs. Further differences in effect sizes resulted from variability in the exact specifiers used in experimental graphs. Minimal differences were obtained among graphs that used position, length, or angle as specifiers. However, graphs that used area or volume to represent quantitative values were associated with consistently worse performance than found with other formats. PMID- 1459566 TI - Distance and organization in multifunction displays. AB - One approach to organizing information in a multifunction display (MFD) is to place related screens of information closer to each other. This study identified three metrics that could be used to operationalize the concept of distance in an MFD. The proposed distance metrics-navigational (the number of choice points lying between two screens), organizational (the hierarchical structure of the data base), and the cognitive (the user's perception of relationships among screens)-were empirically examined by using a simulated, hierarchically arranged, menu-driven MFD in an aviation context. Subjects engaged in two tasks that required them to access different target screens from various starting screens in a 290-screen MFD. The tasks differed in the navigational mechanisms subjects were allowed to use to navigate around the MFD and the relationships between the starting and target screens. The results suggest that the three distance metrics are meaningful within the context of a multifunction display. PMID- 1459567 TI - Using stereokinetic effect to convey depth: computationally efficient depth-from motion displays. AB - Recent developments in microelectronics have encouraged the use of 3D data bases to create compelling volumetric renderings of graphical objects. However, even with the computational capabilities of current-generation graphical systems, real time displays of such objects are difficult, particularly when dynamic spatial transformations are involved. In this paper we discuss a type of visual stimulus (the stereokinetic effect display) that is computationally far less complex than a true three-dimensional transformation but yields an equally compelling depth impression, often perceptually indiscriminable from the true spatial transformation. Several possible applications for this technique are discussed (e.g., animating contour maps and air traffic control displays so as to evoke accurate depth percepts). PMID- 1459568 TI - Spatial judgments with monoscopic and stereoscopic presentation of perspective displays. AB - Spatial judgments with monoscopic and stereoscopic presentation of perspective displays were investigated in the present study. The stimulus configuration emulated a visual scene consisting of a volume of airspace above a ground reference plane. Two target symbols were situated at various positions in the space, and observers were instructed to identify the relative depth or altitude of the two symbols. Three viewing orientations (15, 45, or 90 deg elevation angle) were implemented in the perspective projection. In the monoscopic view, depth cues in size, brightness, occlusion, and linear perspective were provided in the format. In the stereoscopic view, binocular disparity was added along the line of sight from the center of projection to reinforce the relative depth in the visual scene. Results revealed that spatial judgments were affected by manipulation of the relative spatial positions of the two target symbols and by the interaction between relative position and viewing orientation. The addition of binocular disparity improved judgments of three-dimensional spatial relationships, and the enhancement was greater when monocular depth cues were less effective and/or ambiguous in recovering the three-dimensional spatial characteristics. PMID- 1459569 TI - Chromaticity and luminance as coding dimensions in visual search. AB - Visual search times were measured as a function of chromaticity and luminance differences between a target and distractor stimuli. Results showed that mean search time increased linearly with the number of distractors if the luminance difference between target and distractors was small but was roughly constant if the luminance difference was large. Similar results were previously found for chromaticity differences. With the number of distractor stimuli held constant, the mean search time decreased with increases in the difference between target and distractors, up to some critical difference. Further increases in target distractor difference had little effect. Results were similar for targets defined by luminance and chromaticity. There was some advantage to combining luminance differences with chromaticity differences when the target was dimmer than the distractors. Generally there was no advantage for combining a chromaticity difference with a luminance difference when the target was brighter than the distractors. PMID- 1459570 TI - Visibility of transmissive liquid crystal displays under dynamic lighting conditions. AB - Liquid crystal displays maintain superior contrast under bright sunlight conditions compared with cathode-ray tube displays. This attribute, along with reduced weight, volume, and power requirements, make liquid crystal displays especially desirable for use in vehicular applications. The present experiment was designed to determine the luminance requirements for transmissive liquid crystal displays viewed under a wide range of lighting conditions typical of many vehicular environments. Both the ambient illumination incident on the display surface and the forward-field-of-view adaptation luminance were parametrically manipulated. The visual task involved speeded spatial discrimination responses for detection of the gap in a modified Landolt-C acuity target. The results indicate that under the worst lighting conditions tested, a display luminance of approximately 180 cd/m2 yielded asymptotic spatial discrimination performance. The results have been incorporated into a predictive visual performance model for spatial discrimination tasks, which describes the present data well and represents a first step toward a device-independent model of display visibility. PMID- 1459571 TI - Characterization of a 28-kD polymorphic polypeptide detected by two-dimensional electrophoresis of human platelets. AB - A genetic polymorphism of a human platelet polypeptide with a molecular weight of 28 kD detected by two-dimensional electrophoresis was investigated in family and population studies, and cell distribution. The 28-kD polypeptide showed autosomal codominant inheritance of two alleles. The gene frequencies of the two alleles were 0.925 and 0.075, respectively. The 28-kD polypeptide was observed in lymphocytes, neutrophils, eosinophils and monocytes, in addition to platelets. This polypeptide showed good reproducibility in electrophoresis, and appears to be useful as a genetic marker of the human genome in gene mapping and pedigree analysis. PMID- 1459572 TI - Effective population size of a rural village on a large plain (Veggiano, Padua, Italy). AB - A small municipality of about 2,000 inhabitants on a large plain (that of the river Po, which flows across the whole of Northern Italy) was chosen as a model to study the level of genetic isolation of a population which is not delimited by clear geographical barriers. Wright's treatment of isolation by distance was considered to be applicable to this case. Estimates of the non-random component of inbreeding and of the immigration rate in the past showed that, despite the deeply rural environment, the population turnover in the area was extremely rapid. Although the parameter estimates were computed on the basis of little direct empirical evidence, it was concluded that the effective population size was at least one order of magnitude larger than might appear when considering the total population size of the municipality. PMID- 1459573 TI - Deletional types of alpha-thalassaemia in central Java. AB - The frequency of deletional alpha-thalassaemia in a Javanese population sample (n = 103) was investigated at three restriction sites of the alpha-globin gene (BamHI, BglII and RsaI). The overall gene frequency of alpha+ deletional thalassaemia was found to be very low (0.03). Leftward (-alpha 4.2) and rightward (-alpha 3.7) deletions and triplicated genes were present in equal frequency (0.015 and 0.005, respectively). PMID- 1459574 TI - Type II hereditary angio-oedema associated with two mutations in one allele of the C1-inhibitor gene around the reactive-site coding region. AB - The polymerase chain reaction and nucleotide sequence analysis have been used to characterise two point mutations in the eighth exon of one allele of the C1 inhibitor gene in a kindred with type II hereditary angio-oedema (HAE). The mutations comprise a G to A substitution at C1-inhibitor gene nucleotide 16789 and an upstream C to T substitution at nucleotide position 16765. This represents the first report of these two mutations in the same C1-inhibitor allele in type II HAE. The molecular genetic pathogenesis of HAE is discussed in the light of these findings. PMID- 1459575 TI - Serological identification of HLA-B13 subtypes. AB - A serological approach is used to confirm subtypes of HLA-B13 originally observed by one-dimensional isoelectric focusing (1D-IEF). Sixty anti-B13 alloantibody sera were screened against Chinese panel cells. Two clusters of sera showing distinct reactive patterns were identified. One is a shorter reactive pattern than the other. Using these serological reaction patterns, the B13 antigen can be divided into two subtypes, B13.1 and B13.2, in the Chinese population. These serological subtypes appear to correlate well with the 1D-IEF patterns of B13 subtypes. The serological subtyping is also in agreement with the differences in nucleotide sequence previously determined to exist in B13 antigen subtypes. Family studies show that both B13.1 and B13.2 segregate as HLA-B locus alleles. Gene frequencies for B13.1 and B13.2 were 0.0676 and 0.0612, respectively, in our study population of 337 southern Han Chinese. PMID- 1459576 TI - Distribution of ORM1, C6, C7 and APO C-II allele frequencies in populations from mainland Italy and Sardinia. AB - The genetic variation of the human plasma proteins ORM1, C6, C7 and APO C-II was investigated by isoelectric focusing followed by immunoblotting in populations from mainland Italy and Sardinia. The frequencies of ORM1*1 were 0.621 and 0.564, while those of C6*A were 0.657 and 0.706 on mainland Italy and in Sardinia, respectively. In the Roman sample, 8 heterozygotes with C6 variant alleles were encountered, while none were observed in Sardinians. For C7 and APO C-II a number of heterozygotes with the rare alleles C7*2 and APO C-II*2 were found, but their frequency did not reach polymorphic levels in either population. The two populations showed a significant difference in the gene frequencies distribution for ORM1. PMID- 1459577 TI - PI and TF subtypes in Chuetas (Majorcan Jews). AB - PI and TF subtypes were studied in a sample of 137 individuals of the Chueta population. In addition to the PI*M alleles, PI*S, PI*Z, and PI*F were observed in the PI system. In the TF system no TF*B or TF*D alleles were found. PI results were compared with those of some Jewish and non-Jewish populations. The relatively high frequency of PI*S is indicative of a substantial Spanish influence. There are no previous data available on TF*C subtypes in Jews. The very low TF*C3 frequency in Chuetas (lower than in Spain) indicates that this allele may be extremely rare or absent in other Jewish populations. PMID- 1459578 TI - Blood groups in relation to carcinoma of cervix uteri. AB - Data are presented on AB0 and RhD blood groups in 186 patients suffering from carcinoma of cervix uteri and 274 controls from Delhi, India. A strong association is observed between carcinoma patients and blood group A, and a slightly weaker association with blood group B. There is no significant association with RhD blood group. The available data in other populations confirm the association with AB0 blood group. PMID- 1459580 TI - The inverted Y-chromosome polymorphism in the Gujarati Muslim Indian population of South Africa has a single origin. AB - Y-specific polymorphisms were studied in Gujarati Muslim Indians possessing a Y chromosome pericentric inversion [inv(Y)] in an attempt to prove a common genetic origin for the inversion. The p49a/TaqI and p49a/PvuII haplotypes were determined for 9 normal and 8 inv(Y) Gujarati Muslim men. Men with the inversion possessed identical TaqI and PvuII profiles, as opposed to 7 different TaqI and 8 different PvuII haplotypes observed in the 9 normal men. These results provide conclusive evidence for a common genetic origin of the inverted Y chromosome observed in this Gujarati Muslim community. PMID- 1459579 TI - Glucose-6-phosphate dehydrogenase variants in Hawaii. AB - Sequence analysis has been performed on the DNA of 13 glucose-6-phosphate dehydrogenase (G6PD) deficient males from Hawaii, 6 of Filipino, 6 of Laotian, and 1 of Chinese extraction. Four different mutations were found: A-->T at cDNA nt 835, G-->A at nt 871, C-->T at nt 1360, and G-->A at nt 1388. The mutations at nt 835 and nt 1360 have not been described previously, and the latter, in particular, appears to be relatively common. The nt 1360 mutation changes the same codon as is altered in a previously described mutation, G6PD Andalus. PMID- 1459581 TI - Biochemical characterization of Trop-2, a cell surface molecule expressed by human carcinomas: formal proof that the monoclonal antibodies T16 and MOv-16 recognize Trop-2. AB - Trop-2 is a cell surface structure recognized by the 162-46.2 mAb and expressed by most human carcinomas. Since the 162-46.2 mAb works poorly in immunoprecipitation, to characterize the structure of Trop-2 we searched for other mAbs directed against this molecule. Selection of candidates was performed by analyzing the characteristics of mAbs directed against epithelial cells and by comparing the staining pattern of each mAb with the one of the 162-46.2 on frozen sections of human epidermis. Two mAbs, T16 and MOv-16, were selected for further analysis. Formal proof that candidate mAbs reacted with Trop-2 was obtained by comparing their binding patterns to mouse L cells transfected with the Trop-2 gene by genomic DNA transfection and selected by FACS using the FITC-162-46.2 mAb. In immunofluorescence FACS analysis the FITC-T16 and FITC-MOv-16 mAbs specifically stained Trop-2 transfectants. The specificity of binding was confirmed by selective blocking of the staining by the respective unconjugated mAb. Interestingly, cross-blocking studies indicated that the 162-46.2, T16 and MOv-16 mAbs recognize the same epitope or closely spaced ones on the Trop-2 molecule. T16 and MOv-16 efficiently immunoprecipitate Trop-2 from Trop-2 transfectants and from the human cell line OVCA-432, indicating that it is a cell surface glycoprotein, with an apparent molecular weight of 57 kD in non-reducing conditions. A weaker band of 38 kD is often co-precipitated with the 57 kD form in an apparently specific manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459582 TI - A monoclonal antibody produced against a rat esophageal carcinoma cell line reacts with an integrin-like molecule expressed by rat epithelial cells. AB - A monoclonal antibody, designated MAb-5A IIgG1), was generated against a tumorigenic rat esophageal epithelial cell line, B-2T. MAb-5A reacted with a series of non-tumorigenic and tumorigenic epithelial cell lines derived from F 344 rat esophagi or tracheas. However, the highest level of antigen expression was detected on tumorigenic rat epithelial cell lines. A trace amount of antigen was detected in primary cultures of normal rat epithelial cells derived from either esophagi or tracheas. MAb-5A did not react with rat fibroblasts. MAb-5A reacted with B-2T derived tumor tissues propagated in vivo but showed only slight reactivity with normal rat esophageal epithelial tissues. Cell surface radioiodination, extraction and immunoprecipitation experiments were conducted to characterize the antigen molecule. Analysis of the immunoprecipitates by SDS-PAGE and autoradiography revealed two protein bands with mobilities corresponding to approximately 140 and 120 kDa, respectively. Under reducing conditions the 140 kDa band shifted to approximately 120 kDa whereas the 120 kDa band shifted upward to approximately 130 kDa. The non-reduced/reduced mobilities of these bands suggest that they may be members of the integrin family of matrix receptors. A polyclonal antibody to the beta 1 subunit immunoprecipitated two similar bands detected by MAb-5A, further suggesting that the antigen complex may be related to members of the integrin superfamily. PMID- 1459583 TI - Production of a monoclonal antibody that defines the alpha-subunit of the feline IL-2 receptor. AB - A mAb, termed 9F23, to feline Con A-stimulated PBMC was prepared to characterize feline IL-2R. 9F23 was identified by FACS studies, which showed that the antigen was expressed at a high density on Con A-induced feline T cell blasts while 9F23 binding was not detected on nonactivated PBMC or the Crandell feline kidney cell line CRFK. Chemical crosslinking of 125I-IL-2 to membrane IL-2Rs on Con A stimulated feline PBMC under the low-affinity condition resulted in detection of a major 65-kDa band. 9F23 specifically immunoprecipitated the IL-2.IL-2R alpha complex in a cell extract; in contrast, neither anti-human IL-2R alpha H48 nor anti-mouse IL-2R alpha 7D4 reacted with the complex. Moreover, immunoprecipitation with 9F23 of the extract from surface-iodinated Con A stimulated PBMC showed a major 50-55 kDa band. Furthermore, 9F23 had no effect on either IL-2-driven proliferation of the Con A-stimulated PBMC or IL-2 binding. Finally, the expression of feline IL-2R alpha on Con A-stimulated PBMC was up regulated by addition of exogenous IL-2. Thus, 9F23 defines an epitope different from the IL-2 binding site on the alpha-subunit of feline IL-2R. PMID- 1459585 TI - Detection and neutralization of bovine tumor necrosis factor by a monoclonal antibody. AB - Monoclonal antibodies (MAbs) have been produced which are specific for bovine tumor necrosis factor (TNF). MAb BC9 detects bovine TNF in a radioimmunoassay with a detection limit of 24 pg/ml. BC9 also neutralizes the in vitro biological function of bovine recombinant TNF. The activity of 250 ng TNF/ml was entirely neutralized by 1% ascitic fluid. When ascites was added at a saturating concentration (10% ascitic fluid), up to 25 micrograms TNF per ml was neutralized. The neutralizing effect of BC9 was seen in cytotoxic assays using L929 cells and WEHI 164 clone 13 cells. The cytotoxic activity of supernatants from in vitro activated bovine monocytes was entirely blocked by BC9. PMID- 1459584 TI - Lack of effect of recombinant human interferon-alpha 2b on expression of 17-1A antigen on human colon cancer cells. AB - The effects of recombinant human interferon alpha (rHuIFN-alpha 2b) on cell growth, expression of antigenic receptor sites (r) and the affinity constant (Ka) of monoclonal antibody CO 17-1A IgG were studied on two human colorectal cancer cell lines, CX-1 and SW 1116. Cells were incubated with varying concentrations of rHuIFN-alpha 2b prior to exposure to 125I-labeled 17-1A IgG at 37 degrees C following which r and Ka were determined by means of Scatchard plots. Varying concentrations of rHuIFN-alpha 2b had significant growth inhibitory effects on CX 1 and SW 1116 cells, which were time and concentration dependent, but no effects on expression of r and Ka compared to controls. Our data indicate that rHuIFN alpha 2b does not invariably increase the expression of tumor-associated antigens and that this effect may be independent of its antiproliferative activity. The in vitro response or lack thereof of neoplastic cells to rHuIFN-alpha 2b may be useful to identify those patients who potentially might gain from a clinical course of rHuIFN-alpha 2b for either therapeutic or diagnostic purposes. PMID- 1459586 TI - Negative effect of multiple antigen injections on the yield of murine monoclonal antibodies obtained by hybridoma technology. AB - One of the critical steps in the preparation of monoclonal antibodies is the obtainment, by in vivo immunization and boost, of the maximal number of antigen activated B lymphocytes. In hybridoma laboratories, the common procedure is to immunize a group of mice with several antigen injections and use the mouse showing the highest serum antibody titre for the fusion experiment. The observation that the use of mice hyperimmunized with human red blood cells failed to yield a high number of monoclonal antibodies, led us to study the effect of multiple antigen injection prior to the fusion experiment. The results obtained showed that the maximal yields of monoclonal antibodies were obtained using mice that had received only one or two antigen injections while the mice immunized with three antigen injections consistently yielded at least a three-fold reduction in the number of monoclonal antibodies. The negative effect could not be reversed by prolonged resting of the animals and suggests the induction of a tolerance/suppression state which can prevent the final activation step. These results point out to the importance of avoiding the hyperimmunization of mice for the preparation of a high number of monoclonal antibodies by standard hybridoma technology. PMID- 1459587 TI - Cloning hybridomas in a reversible three-dimensional alginate matrix. AB - Alginate is a transparent polymer of guluronic and mannuronic acids that provide a favorable microenvironment for cell growth. Alginate gelation is calcium dependent and temperature independent. To facilitate the isolation of stable and productive antibody-producing hybridomas, we have developed a technique of cloning hybridomas in the three-dimensional alginate matrix. To provide cavities for hybridoma growth, we encorporated 10-15% (v/v) gelatin into the alginate prior to gelation. We have cloned more than 90 monoclonal antibody-producing hybridomas using the alginate matrix. The alginate matrix is readily reversible with the addition of a calcium chelator. The alginate matrix permits efficient cloning in limited incubator space, without the use of a feeder layer, and with minimal amount of medium. The transparent matrix also permits easy screening for clonality and growth. PMID- 1459588 TI - Instability of a hybridoma cell line in a homogeneous continuous perfusion culture system. AB - In this study several analytical techniques were applied to obtain information about the stability of expression, the yield, and the integrity of a monoclonal antibody (Mab) produced by hybridoma cell line RIV6 in a homogeneous continuous perfusion culture system. The total antibody as well as the isotype-specific antibody contents decreased continuously during the course of cultivation, while the viable cell concentration remained constant. The origin of the discrepancy between the Mab contents observed by two enzyme-linked immuno sorbent assay (ELISA) systems during the steady state was due to fragmentation of the IgG molecule, either cytoplasmic or in the culture fluid, as determined by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The IgG-secreting cells as well as the fraction of cells containing a high cytoplasmic IgG content decreased continuously during cultivation. The isoelectric focusing (IEF) pattern showed the appearance of two additional bands after five days of cultivation. This work indicates that cell line RIV6 is unstable in the culture system used, with respect to cell properties and product formation. PMID- 1459589 TI - Cloning and reexpression of a functional human IgM anti-lipid A antibody. AB - The human hybridoma cell line HR78 secretes a human antibody of the IgM isotype directed against bacterial endotoxin. The cell line produces low levels of antibody and, more importantly, the antibody product is likely to be impure since two and perhaps more species of heavy chain are being synthesized as judged by cloning and expression studies. To address these issues, the cell line was used as a source of mRNA for the construction of cDNA libraries and the subsequent isolation of the sequences encoding heavy and light chains. Expression of these chains in a non-immunoglobulin producing murine hybridoma cell line resulted in a monoclonal antibody that bound antigen in a manner essentially identical to that observed for the parental antibody. Moreover, the level of expression of human IgM in selected clones was increased approximately 50-fold over the parental cell line and was comparable to or better than antibody expression by a typical murine hybridoma. PMID- 1459590 TI - Introduction of a segment of Rhizobium meliloti megaplasmid in Escherichia coli slows down its growth in minimal medium. PMID- 1459591 TI - Intraspecific sexual isolation in Drosophila. AB - Intraspecific sexual isolation was examined among wild strains of Drosophila malerkotliana, D. parabipectinata and D. pseudoananassae by multiple-choice method in Elens-Wattiaux mating chamber. In D. pseudoananassae, mating between two strains tested was random and isolation estimate was close to one. In one out of 6 crosses, involving geographic strains of D. malerkotliana, there was significant deviation from randomness and isolation estimate remained low which shows non-random (preferential or positive assortative) mating. In D. parabipectinata, the deviation from randomness was statistically significant due to higher number of homogamic matings in three crosses involving wild strains derived from geographically distant places and isolation estimate remained low in these crosses. The results provide evidence for incipient sexual isolation within D. malerkotliana and D. parabipectinata as a result of genetic divergence. PMID- 1459592 TI - Gonado-modulatory effects of high humidity is pineal dependent in Indian palm squirrel Funambulus pennanti (Wroughton). AB - F. pennanti presented a clear biphasic pineal mediated seasonal sexual cycle. This sexual cycle was essentially characterised by a very short period of sexual quiescence with an arrest of spermatogenesis during October-November. A small but clear decrease in sexual activity was also observed during March-April. This decrease in sexual activity, however, had no quantifiable effect on spermatogenesis. Sexual recrudescence was observed from December-January. The testes remained sexually active from January till September. Almost an inverse relationship was observed between pineal and testicular weight. Pinealectomy, however, prevented naturally induced gonadal regression during both the periods, i.e. September-November and February-April. Exposure of animals to high RH (80 +/ 4%) during sexually active phase induced a steep regression in testicular weight of sham-operated animals even in the presence of gonad stimulatory long photoperiod (16L:8D) and high temperature (40 degrees +/- 5 degrees C) while exposure of animals to moderate RH (65 +/- 5%) during sexual regression phase partially prevented testicular regression even in presence of inhibitory short photoperiod (11L:13D) and normal environmental temperature (30 degrees +/- 5 degrees C). Pinealectomized animals, neither exhibited testicular regression in February-March nor had involuted testes in September-October, thus, suggesting that the effect of humidity is mediated via the pineal gland. PMID- 1459593 TI - Localization and detection of ovarian follicular fluid protein in follicles of human ovaries. AB - Human ovarian follicular fluid protein has been partially purified and the active fraction designated as hGF2. Using specific polyclonal antiserum to hGF2, it was observed to be localized immunohistochemically in the granulosa cells of medium but not large follicles of human ovary. The hGF2 levels were estimated by ELISA in serum and follicular fluid of 10 gonadotropin-stimulated women recruited for IVF-ET programme. The results revealed a 3-fold increase in the concentration of hGF2 in follicular fluid compared to that in serum of these patients. These data indicate that the protein is secreted by granulosa cells and plays an important role in the regulation of follicular maturation and ovulation. PMID- 1459594 TI - Age related modulation of circadian time structure of blood, plasma and tissue variables in male domestic fowls. AB - To study modulation of circadian time structure of 11 blood, plasma and tissue variables in male domestic fowls, as a function of age, three experiments were made in one-day-old fowls (72) standardized by 12L:12D. In the first experiment, at 6 week age, 24 birds were killed by decapitation, four each at six different circadian stages (2, 6, 10, 14, 18 and 22 hr after light onset, HALO). Equal number of birds were killed at similar circadian stages at the age of 12 and 18 week in the second and the third experiments, respectively. Age affected both, the circadian patterns and the mesors (24 hr mean values). The circadian pattern included amplitude (half of the total extent of variation) and acrophase (estimated time of peak) for each variable. The results clearly suggest that the pattern of circadian rhythm may vary as a function of age of the bird. PMID- 1459595 TI - Electrokinetic behaviour of subpopulations of T lymphocytes in allografted mice. AB - In AKR(H-2k) mice transplanted with DBA/2(H-2d) skin grafts, the mean electrophoretic mobilities (EPM) of total lymph node cells (LNC) and T cells were significantly reduced. Subpopulations of T lymphocytes, viz. CD4- (CD8- (CD4+) T cells were obtained by depletion treatment of T cells with monoclonal antibodies specific for these surface antigens and complement. Determination of EPM of these two subpopulations revealed that the electrokinetic change following immunostimulation equally afflicted these two subpopulations. These data thus confirmed that CD4+ as well as CD8+ T cells were activated in MHC unmatched allograft rejection. PMID- 1459596 TI - Effect of chemically different calcium antagonists on lipid profile in rats fed on a high fat diet. AB - Different classes of calcium antagonists, viz. verapamil (diphenylalkylamine), diltiazem (benzothiazepine), nifedipine, felodipine and nimodipine (dihydropyridines), were examined for their effects on lipid profile in rats. Clofibrate was the reference standard. Clofibrate significantly prevented the rise of serum triglycerides and total cholesterol produced by high fat diet and raised antiatherogenic index to 1.6 times than that of high fat diet controls. Of the calcium antagonists studied, felodipine was most effective in preventing the rise of serum triglycerides and total cholesterol in high fat diet fed rats. Felodipine's antiatherogenic index was very high (886%)--much more than that of clofibrate (303%). Diltiazem and nimodipine which also significantly prevented the rise in triglycerides and total cholesterol produced by high fat diet had a moderately beneficial antiatherogenic index similar to that of clofibrate. Though verapamil and nifedipine slightly increased the triglyceride levels, total cholesterol levels were reduced only by verapamil and not by nifedipine. Despite this both these drugs moderately raised antiatherogenic index similar to clofibrate. PMID- 1459597 TI - Effect of variations in temperature of injected saline on early development of chick embryo. AB - Development of chick embryo is sensitive to the incubation temperature and increase or decrease in incubation temperature produces defect in development but the effect of drug solution injected at variable temperatures on developing chick embryo has not been established so far. Fresh embryonated eggs were incubated and saline was administered at various temperatures after 17 hr of incubation. Embryos were harvested to see the effect of temperature variations of injected saline on neural tube formation. Normal neural tube development was seen only at 37 degrees C, hot or cold saline produced maldevelopment of neural tube. Thus it is concluded that any solution or drug which needs to be injected should ideally be used at 37 degrees C, as temperature lower or higher than that may vitiate the results. PMID- 1459598 TI - Respiratory responses and blood sugar level of the crab, Barytelphusa cunicularis (Westwood), exposed to mercury, copper and zinc. AB - Barytelphusa cunicularis (Westwood), a freshwater crab was exposed to mercuric chloride, copper sulphate and zinc sulphate from 0 to 12 hr and the oxygen consumption of the animal was measured in order to study the stress caused by these heavy metals. Normal oxygen consumption was affected by the three heavy metals. Similarly, crabs exposed to sublethal concentrations of the same pollutants for 24, 48, 72 and 96 hr showed an elevation in the blood sugar level with a maximum increase at 48 hr. The results indicate a switch towards glycolysis in order to overcome the anaerobic stress caused by the heavy metals. PMID- 1459599 TI - Distillery effluent treatment using Artemia. AB - Artemia functions as living filter for the secondary treatment of distillery effluent, which reduces up to 69% of the total solids and 33.34% of BOD in the saline medium of 60 ppt. Chemical analysis of diluted effluent after treatment with Artemia showed a significant (P less than 0.001) decrease in the electrical conductivity, calcium and potassium values. However, an increase in sodium concentration and pH values, was recorded during experiment. PMID- 1459600 TI - Potentiation of hypoglycemic response of glibenclamide by piroxicam in rats and humans. AB - Influence of piroxicam (PX) on glibenclamide (GL) induced hypoglycemia has been studied in rats, healthy human volunteers and diabetics. GL per se has significantly reduced blood sugar levels in rats and in humans. PX per se has significantly reduced BSLs, in diabetics, while having no significant influence on blood sugar level in rats and healthy human volunteers. Prior administration of PX has potentiated the hypoglycemic effect of GL in rats, healthy human volunteers and diabetics. GL, PX + GL administration have also significantly influenced the glucose tolerance test (GTT) in healthy human volunteers. PMID- 1459601 TI - Alterations in metabolic activity of Cysticercus fasciolaris on some anthelmintic treatments. AB - Effect of candidate compounds 81-470 i.e. methyl [5[4-(2-pyridinyl)-1 piperazinyl]carbonyl]-1H-benzimidazole-2-yl]- carbamate and 86-162 i.e. methyl 5(6)-(alpha-hydroxyphenyl methyl) benzimidazole-2-carbamate along with reference drugs mebendazole and praziquantel on energy metabolism of C. fasciolaris recovered from rats treated with single dose of 500 mg/kg, ip was investigated. All the drugs significantly lowered the rate of uptake of glucose and alanine by the parasite. Suppression in the formation of lactate, the major end-product, was also noticed. Nonetheless the ratio of lactate produced versus the substrates consumed was not substantially affected. The recovered cysticerci also possessed less glycogen and ATP compared to the normal parasites. Although the effects exerted by the drugs were of the identical nature, they significantly differed in the magnitude of their action. Mebendazole followed by praziquantel maximally affected all the above metabolic activities while 86-162 proved to be the weakest in action. The results suggest that the examined drugs exert their chemotherapeutic activity by interfering with uptake of glucose and alanine but do not significantly alter their catabolism. PMID- 1459602 TI - Mechanisms of Bacillus cereus enteropathy. AB - Three strains of Bacillus cereus isolated from sausages (Salami and Trekker, RANBAC, Ranchi) produced enterotoxin which caused vascular permeability in skin and haemorrhage in the ligated ileal loops of rabbits. Histopathological studies revealed haemorrhage and congestion in submucosa, mononuclear cell infiltration in lamina propria and submucosa and villous atrophy. Histochemical studies ruled out the effect on mitochondrial enzymes of intestinal epithelial cells. Purified enterotoxin given intradermally to rabbits caused severe necrotic reaction at the site of injection and death within 4 hr. Histopathological changes observed in liver included congestion of portal veins and sinusoids, vacuolar degeneration of hepatocytes, and hyperplasia of bile ducts. These suggested that B. cereus enterotoxin affected the capillaries of blood vessels locally and also systemically resulting into release of proteinaceous exudates and red blood cells. PMID- 1459603 TI - Correlative studies on mating speed and metric traits in Drosophila malerkotliana. AB - Relationship between mating speed, an important component of fitness, and morphological characters such as lengths of wing, femur, tibia and first tarsus have been analysed in D. malerkotliana. Flies mating first have longer wings and forelegs and mating flies have lower coefficient of variability in wing length than nonmating ones. Age seems to have no detectable effect on the relationship between these metric traits and mating speed. PMID- 1459604 TI - Antimutagenic activity of Terminalia chebula (myroblan) in Salmonella typhimurium. AB - Antimutagenicity of water and chloroform extracts of dried myroblan Terminalia chebula was determined against two direct acting mutagens, sodium azide and 4 nitro-o-phenylenediamine (NPD) in strains TA100 and TA1535, and TA97a and TA98 of Salmonella typhimurium respectively and S9-dependent mutagen 2-aminofluorene (2 AF) in TA97a, TA98 and TA100 strains. Water extract reduced NPD as well as 2-AF induced his+ revertants significantly but did not have any perceptible effect against sodium azide included his+ revertants in TA100 and TA1535 strains of S. typhimurium. The pre-incubation studies, where the extract was incubated at 37 degrees C for 30 min with the said mutagen prior to plating, enhanced the inhibitory effect. Autoclaving the water extract reduced the inhibitory effect but the reduction in the effect was not significant. No inhibitory effect was observed in any of the strains and against any of the test mutagens with chloroform extract. PMID- 1459605 TI - Effect of RMI 12,936, an antiprogestational steroid on decidual cell reaction and embryos in rat. AB - Subcutaneous administration of RMI 12,936 at a dose level of 2 mg/rat on day 5 of unilaterally pregnant rat having trauma-induced decidual cell reaction (DCR) in the contralateral uterine horn, suppresses DCR, induces resorption of implanted embryos and leads to decrease in the plasma level of progesterone. Progesterone replacement (D 5-8) in this situation reverses DCR suppressive effect of RMI 12,936 but fails to prevent resorption of implanted embryos. It is concluded that possibly the drug simultaneously exerts embryotoxic as well as luteolytic effects, but these effects are independent. PMID- 1459606 TI - Evaluation of Biken test for detection of Salmonella enterotoxin. AB - Biken test by using antiserum to purified Salmonella enterotoxin (SE) was standardized and carried out to screen salmonellae for their enterotoxigenicity. As many as 101 strains of Salmonella belonging to 15 different serotypes isolated from foods of animal origin were subjected to Biken test. Of these, 68 (67.32%) were found seropositive. The test correlated with the rabbit ligated ileal loop (RLIL) test completely for the detection of enterotoxin producing salmonellae with 24 test strains. However, 5 of the 13 strains which were negative in the RLIL test, yielded positive results with the Biken test. PMID- 1459607 TI - Effect of graded doses of naloxone on renal function in canine hemorrhagic shock. AB - All the parameters of renal function (inulin clearance, para amino hippuric acid clearance and urine flow) which were depressed during experimentally induced hemorrhagic shock in dogs improved significantly in addition to improvement in mean arterial pressure (MAP) after bolus administration (iv) of 1 or 2 mg/kg naloxone. A smaller dose (0.5 mg/kg) of naloxone, however, did not improve the renal function. Even renal arterial injection of the same dose of naloxone showed no improvement in the renal function. In both these cases the improvement in the MAP was significantly less as compared to other groups of animals which received 1 or 2 mg/kg naloxone. It may be concluded that (a) naloxone at doses of 1 or 2 mg/kg improved the renal function by improving MAP and (b) naloxone has no direct action on renal vasculature. PMID- 1459608 TI - Neurophysiological alterations following fluvalinate administration in mice. AB - Median lethal dose (LD50) of fluvalinate (Marvik 25EC) was 105 (94.6-116.5 mg/kg, ip) in albino mice. Gross observable signs were dose dependent and indicative of central and peripheral nervous system stimulation. Fluvalinate, at 10.5 and 21.0 mg/kg, ip doses in mice, facilitated maximal electroshock seizures, reduced reaction time in analgesic test and enhanced duration of ether anaesthesia. Acute and subacute (7 days) treatment at lower and higher doses enhanced pentobarbitone sleeping time. Acute and subacute treatment (7 days) with phenobarbitone (50 mg/kg, ip) prior to fluvalinate enhanced toxicity of fluvalinate. PMID- 1459609 TI - Effect of malathion on antioxidant defence system in human fetus--an in vitro study. AB - Malathion under in vitro condition even at lower concentration (250 ppm) altered the level of enzymes associated with glutathione cycle and antioxidant defence system in human fetal brain and liver. Such changes involved alterations in glutathione status and extent of lipid peroxidation. The inhibitory effect of malathion was dose dependent in case of human fetal brain and was more vulnerable than fetal liver. This alteration (inhibition or activation) was maximum in case of tissues from fetuses of early period of development, suggesting greater susceptibility of human fetus towards this organophosphorus insecticide. PMID- 1459610 TI - Effect of antioxidants on adenosine triphosphatase activity of brain and heart in male mice during ageing. AB - The present study deals with the effect of butylated hydroxy anisole, propyl gallate and alpha-tocopherol on ATPase activity of brain and heart in ageing male mice. The activity of both the tissues significantly increased during pre reproductive and reproductive phases. However, during the post-reproductive phase, ATPase activity of heart increased while that of the brain remained unaltered. The enhanced activity could be attributed to interference by the antioxidants in cellular metabolism and/or their free radical scavenging effect. PMID- 1459611 TI - Characterization of a continuous lymphocyte cell line derived from BALB/c mice inoculated with a recombinant Moloney murine leukemia virus-TB. AB - Neonatal BALB/c mice were inoculated (ip) with a recombinant Moloney murine leukemia virus-TB. Majority of the inoculated mice developed lymphoma within 5-7 months post infection. The cells from splenic lymphomas were cultured and 3 continuous cell lines (GP1, GP2 and GP3) developed. GP1 was single cell cloned and characterized. Based on Thy 1.2 (98.4%) phenotypic marker, the cell line was categorized as T cell line. The percent positivity for different cell surface markers on analysis with FACS was 98.4, 4.8, 5.5, 2.2, 1.8, 1.2 and 9.5 for Thy 1.2, mu, L3T4, Lyt2, Ia, IL2R and PNA receptor, respectively. A total of 16.5% GP1 cells was also positive for Moloney murine leukemia virus envelope protein (gp 70). Incomplete retrovirus like particles were demonstrated in the cytoplasm of GP1 cells by electron microscopy. The cell line on inoculation(ip) in neonatal BALB/c mice produced lymphomic lesions in almost all the vital organs of the mice. PMID- 1459612 TI - Antigenic analysis of purified surface antigens of filarial nematode Setaria digitata. AB - The surface antigens of S. digitata were isolated by treatment with Triton X-100. In non SDS-PAGE the surface antigen preparation resolved into more than 6 protein bands. Electroelution of gel slices corresponding to the protein bands with relative mobilities 0.09, 0.32, 0.41, 0.53, 0.61 and 0.76 gave 6 purified surface antigen fractions (SAF). Analysis of SAFs by SDS-PAGE showed that the proteins with molecular weights 17, 29 and 36 KD were the three major polypeptides and different combination of these gave rise to the 6 native surface proteins. The 29 KD protein existed as a monomer and as cross-linked with the 17 and 36 KD proteins. All surface antigen fractions showed antigenicity, where as 29 KD protein remained as a high avidity surface antigen. PMID- 1459613 TI - Diosgenin--a growth stimulator of mammary gland of ovariectomized mouse. AB - Estrogenic action of diosgenin on the mammary epithelium of ovariectomized (OVX) mouse has been reported. Diosgenin when administered (sc) at the dose levels of 20 and 40 mg/kg body weight for a period of 15 days stimulated the growth of mammary epithelium. This was indicated by the increase in DNA content, increase in number of ducts and appearance of terminal endbuds. There was a significant increase in the mammary development scores in the presence of diosgenin. Concomitant treatment of estrogen and diosgenin showed augmentation of estrogenic effect of diosgenin especially at the higher dose level (40 mg/kg body wt). Diosgenin showed a lack of progesterogenic action as was apparent from the absence of alveolar development even in the presence of exogenous estrogen. PMID- 1459614 TI - Lytic effect of Bacillus subtilis elastase on gram-positive and negative bacteria. AB - Elastase of B. subtilis 6a caused lysis of freshly grown cells of Gram-negative (Proteus vulgaris, Klebsiella pneumoniae, Salmonella typhi and Pseudomonas aeruginosa and Gram-positive (B. subtilis) bacteria. Heat killed and lyophilised Gram-positive and negative bacteria showed higher sensitivity to elastase. Both Gram-negative and Gram-positive bacteria were lysed maximally by elastase at pH 8.0. At this pH, activity of elastase was maximum in Tris-HCl and glycine-NaOH buffers followed by Tris-maleate and cacodylate buffers. PMID- 1459615 TI - Modulatory effects of metanil yellow on immunity in rodents. AB - Pathomorphological and immunological studies were carried out on rodents following oral administration of 0, 0.1, 0.25 and 0.5% (w/w) metanil yellow, mixed in diet, for 30 days. No significant change in hematologic parameters and histologic architecture of liver, kidney, mesenteric lymph node, thymus and urinary bladder was observed except for mild desquamation of intestinal villi and moderate changes in Peyer's patches of small intestine with higher doses. Among immunological parameters, significant enhancement in the primary humoral immune response (anti-SRBC IgM plaque forming cells of spleen) was observed with the lowest dose of metanil yellow while higher doses produced opposing effects. An elevated cutaneous delayed type hypersensitivity (DTH) reaction to SRBC was seen in 0.1% metanil yellow treated animals but higher doses did not influence the reaction. The treatment also caused changes in functional capabilities of macrophages. Although these immune alterations could hardly influence the local immunity of gut, as measured by the capacity of animals to cause rejection of Nippostrongylus brasiliensis parasite, the potential to modulate the immunity in general by metanil yellow however assumes considerable biological significance. PMID- 1459616 TI - Toxic effects of different concentrations of dimethoate on lysosomal enzymes of female albino rats. AB - The effect of three different concentrations of dimethoate on the activity of certain lysosomal enzymes, viz. beta-glucuronidase, beta-N-acetylglucosaminidase, cathepsin B and cathepsin D in serum, skin, liver, kidney and spleen and the stability of liver and kidney lysosomes was studied in female albino rats. The activity of beta-glucuronidase, beta-N-acetylglucosaminidase, cathepsin D was found to increase in serum and tissues in higher concentration (2.25 mg/100 g body weight) of dimethoate treated rats. A significant increase in the rate of release of beta-glucuronidase was found in the liver and kidney of higher concentration of dimethoate treated rats compared to controls. The results demonstrate that the activity of lysosomal enzymes increased in higher concentration of dimethoate treated rats than the lower concentration (0.56 mg/100 g body weight) of dimethoate treated rats. PMID- 1459617 TI - Effect of styrene on testicular enzymes of growing rat. AB - Effect of styrene (100 or 200 mg/kg body wt/day) for 60 days was observed on testicular enzymes of postnatally maturing rats. A significant decrease in epididymal spermatozoa count was observed only at 200 mg/kg body weight dose. Activities of testicular sorbitol dehydrogenase and acid phosphatase decreased while activities of lactate dehydrogenase, beta-glucuronidase, glucose-6 phosphate dehydrogenase, and gamma-glutamyl transpeptidase significantly increased only in animals exposed to styrene at a dose of 200 mg/kg body weight. The results suggest that exposure to high dose of styrene during developmental period alters the activities of enzymes associated with specific cell type of testis. PMID- 1459618 TI - Trichloroethylene toxicity in mice: a biochemical, hematological and pathological assessment. AB - Oral administration of trichloroethylene (TCE; 0, 500, 1000 and 2000 mg/kg/day) to male mice once daily, 5 days a week for a period of 28 days, caused a significant increase in liver weight, degeneration/necrosis of hepatocytes and characteristics proliferation of endothelial cells of hepatic sinusoids. Increase in kidney weight, glomerular nephrosis, degeneration/desquamation of tubular epithelium and characteristic amyloid deposition in glomeruli were observed only in the group of mice treated with 2000 mg/kg TCE. These changes occurred concurrently with a significant increase in total protein and free sulphydryl contents, elevated activities of acid phosphatase and catalase and decreased activity of delta-aminolevulinic acid dehydratase (delta-ALAD) indicating the sensitivity of liver and kidney as target tissues in TCE-toxicity. Hematological studies showed a significant increase in RBC counts and a reduction in WBC counts without any statistically significant change in the hemoglobin, urea nitrogen, creatinine and uric acid levels in the blood of TCE-exposed mice. A dose-related increase in cell density and acid phosphatase activity with a parallel significant decrease in the activity of delta-ALAD were observed in the bone marrow, which appear to be responsible for hematological alterations in TCE exposed mice. The results suggest that early metabolic, pathological and hematological perturbations following a short-term exposure of TCE in mice, can provide the basis for its documented potential for chronic effects like blood dyscrasia and cancer. PMID- 1459619 TI - Hepatic mixed function oxidase system and effect of phenobarbital, 3 methylcholanthrene and 1, 1, 1-trichloro-2, 2-bis(p-chlorophenyl)ethane in developing chickens. AB - Contents of hepatic microsomal protein, aminopyrine N-demethylase, acetanilide hydroxylase, aniline hydroxylase, hydrogen peroxide formation, cytochrome-c reductase, cytochrome b5 and cytochrome P-450 were examined in control, phenobarbital (PB), 3-methylcholanthrene (3-MC) and 1, 1, 1-trichloro-2, 2-bis(p chlorophenyl)ethane (DDT) treated group of 1-28 days old chickens. Increase in aminopyrine N-demethylase, acetanilide hydroxylase, aniline hydroxylase, cytochrome-c-reductase, cytochrome b5 and cytochrome P-450 was noticed at all stages of development during administration of PB and 3-MC. But these enzyme activities were not always paralleled by increase in age. Aminopyrine N demethylase was increased in early stages only during DDT administration, which indicates that the form of cytochrome P-450, responsible for aminopyrine N demethylation is present in early stages only. However, acetanilide hydroxylase was decreased in all stages of development, in postnatal development the basal activities of the enzymes for various substrates do not exhibit identical pattern, the degree of inducibility by inducers varied in relation to age of animal. Hydrogen peroxide formation increased in all stages of developing chickens due to the administration of PB and DDT. It however decreased due to 3 MC administration which may be due to induction of high spin cytochrome P-450. PMID- 1459620 TI - Acidic and basic protein contents in Gastrocnemii and pectoralis muscles of chick under denervation and work-induced stress conditions. AB - Biochemical estimation of acidic and basic proteins of chick gastrocnemii (G. externus, G. medius and G. internus) and pectoralis muscles has been done under normal, denervated and work stress conditions from 1-56 days of postnatal growth. The reciprocal relationship of the two protein groups is clearly established. It is evident that muscle denervation acts as a stimulant for proteosynthetic activities and probably may also be an inhibitory factor for protein degradative reactions. During work overload stress, the rapid growth of muscles has been related to high rate of contractile activity. PMID- 1459621 TI - Hypolipidemic action of taurine in rats. AB - The effect of taurine on the serum and liver cholesterol and triglyceride levels was studied in rats fed cholesterol plus cholic acid. Four groups of 4 weeks old rats were fed control diet, hypercholesterolemic diet (HCD), HCD + 1% taurine or HCD + 2% taurine for 8 weeks. Addition of taurine in HCD diet showed a significant reduction not only in serum total cholesterol and triglyceride levels but also in liver total cholesterol, lipid and triglyceride contents compared to the animals fed HCD alone. Histological examination of organs of these animals showed severe fatty vacuolation in livers and signet ring type vacuolation in kidneys of rats fed HCD. Taurine showed ameliorating effect on these abnormalities. The animals fed taurine in HCD also showed increased bile and sterol excretion in faeces compared to rats fed HCD alone. Taurine showed significant hypocholesterolemia in rats probably by enhancing the catabolism of cholesterol and reducing the absorption of dietary cholesterol. PMID- 1459622 TI - Effect of some natural pesticides on entomogenous muscardine fungi. AB - Five commercial preparations of natural pesticides were tested for in vitro compatibility with muscardine fungi, Beauveria brongniartii and Metarhizium anisopliae. Neemark (azadirachtin) was found compatible with both the fungi. Phytoallexin, the natural fungicide, significantly inhibited the growth of both the fungi, while other natural pesticides showed moderate to severe inhibition. PMID- 1459623 TI - Neurodepressive action of a piscicidal glycoside of plant, Aesculus indica (Colebr.) in fish. AB - Sublethal concentration (2.6 mg/l) of a triterpene based piscicidal glycoside of A. indica damaged the neurons, fibre tracts and central correlation sites for gustatory, tactile and visceral sensory impulses in medulla oblongata of fish after prolonged poisoning. The fear, sinking to bottom, lack of schooling and non discriminatory pattern in treated fish were because of neurodepression. The jerky movement, ventilatory inefficiency, swallowing air bubbles and light pinkness of gills were due to the degradation of respiratory centres in the vagal lobes of toxified fish. PMID- 1459624 TI - Effect of banana stem juice on biochemical changes in liver of normal and hyperoxaluric rats. AB - Influence of stem extract of banana (family Musaceae), was studied on glycolic acid oxidase (GAO) and lactate dehydrogenase enzymes, calcium, phosphorus, oxalate and glycolic acid in liver tissues of sodium glycolate-induced hyperoxaluric rats. Activity of GAO was significantly lowered in the extract treated rats compared to that of the glycolate-fed rats. LDH increased significantly in glycolate administered rats when compared with the extract treated rats. The levels of calcium, phosphorus, oxalate and glycolic acid during hyperoxaluric state showed remarkable alterations in liver tissue. PMID- 1459625 TI - Effect of dietary salt (NaCl) supplementation on urinary profile of guinea pigs (Cavia porcellus). AB - Sodium chloride supplementation (120 mg/kg of body weight/day) for 12 days increased the urinary excretion of calcium from 91.6 +/- 9.0 to 159.4 +/- 16.0 mumol/day and of sulphate from 266.8 +/- 24.5 to 1176.9 +/- 87.2 mumol/day in guinea pigs. The stone risk due to increased urinary calcium excretion could possibly be counterbalanced by increasing urinary sulphate excretion. High salt intake, thus, could not increase the risk of stone formation. PMID- 1459626 TI - A comparison of vessel sensitivity and vessel constant in oxygen uptake determination with pure oxygen and air as gaseous media. AB - Air proved to be a superior gaseous medium to pure oxygen used for oxygen uptake study in the Warburg apparatus Recording of volume change (vessel sensitivity method) was the only correct method of recording the oxygen uptake. It is concluded that the volume change method should be followed for recording oxygen uptake by Warburg apparatus and pure oxygen should not be used as a gaseous medium. PMID- 1459627 TI - Replicative activity of X-chromosome and autosomes of Drosophila melanogaster in autosomal hyperploids and the problem of dosage compensation. AB - Replicative behaviour of two hyperploid autosomal arms (2L and 3L) of D. melanogaster has been analysed by 3H-thymidine autoradiography. Results reveal that hyperploid autosomal arms (2L-trisomy or 3L-trisomy) replicate synchronously with other disomic non-homologous chromosome arms i.e. there is no asynchrony in the initial mid or late phase of replication patterns between the trisomic 2L or trisomic 3L and disomic arms, suggesting that the extra dose of an autosomal arm can not alter the inherent pattern of replication of that arm. Results further reveal that 2L-trisomy or 3L-trisomy does not impart any influence on X chromosomal replication in either sex. It is suggested from these results that change in the genomic dose of autosome does not play any role in modulating the replicative organization of the autosomes, 2L and 3L. Thus, although a regulatory mechanism of autosomal dosage compensation does exist for Drosophila, the hierarchy of genetic programming of regulation for X-chromosomal and autosomal dosage compensation might be different. Neither hypertranscriptive activity nor faster replication pattern of the male X-chromosome is influenced by 2L- or 3L trisomy. PMID- 1459628 TI - Differential response of testis and serum gonadotropins to testosterone in rats treated with a gonadotropin releasing hormone antagonist or estradiol 17 beta. AB - Adult rats treated with a GnRH antagonist (Ac D2Nal1, D4Cl Phe2, DTrp3, DArg6, DAla10 GnRH; code: 103-289-10, National Institutes of Health, USA) for 5 weeks (250 micrograms/kg b.w) showed multiple degrees of impairment and atrophy of the genital organs concomitant with decreased serum levels of testosterone, LH and FSH. Inhibition of spermatogenesis was characterized by germ cell degeneration and overall decline in different cell numbers and in particular, spermatids of any kind were completely absent. Testosterone supplementation (60 micrograms/rat/day, sc) to GnRH antagonist treated rats, for the same period, significantly elevated the weights of the sex organs, and the serum levels of hormones. Spermatogenesis was improved both qualitatively and quantitatively; albeit failed to be restored back to control levels. Treatment with estradiol 17 beta (1 microgram/rat/day) for 5 weeks had insignificant effect on spermatogenesis but the weights of the genital organs (seminal vesicles by 19% and ventral prostate by 40%) and the levels of serum hormones (LH by 24%, FSH 22% and testosterone by 25%) were otherwise reduced. Administration of testosterone either alone or in combination with estradiol 17 beta had only a marginal effect on spermatogenesis or on other reproductive parameters. The results indicate a positive shift in the response of the testis and serum levels of gonadotropins to testosterone supplementation in rats treated with either GnRH antagonist or estradiol 17 beta. PMID- 1459629 TI - Sperm production and fertility of bonnet monkeys (Macaca radiata) following immunization with ovine follicle stimulating hormone. AB - Adult male bonnet monkeys were rendered oligospermic but not azoospermic following active immunization with ovine follicle stimulating hormone. The percentage of sperms in the semen having good motility was reduced with a concomitant increase in the sperm ATPase activity. Eight out of 10 immunized monkeys failed to impregnate females of proven fertility after mating for consecutive three cycles while the remaining two impregnated the cohabitated females during the third cycle at a time when the antibody titer was reduced. Active immunization with ovine follicle stimulating hormone may not produce complete azoospermia but renders adult male monkeys infertile provided sufficient antibody titer is maintained. PMID- 1459630 TI - Neuropharmacology of amide derivatives of P-GABA. AB - Three lipophilic amide derivatives of phthaloyl-GABA (P-GABA), namely gamma phthalimido N-amyl butyramide (PGA), gamma-phthalimido-N-hexylbutyramide (PGH) and gamma-phthalimido N-phenylbutyramide (PGP), were synthesized and evaluated for their hypnotic and anticonvulsant activities in mice. Both PGA and PGH showed moderate hypnotic activity but PGP had no such action. Picrotoxin (0.08 mg/kg) a non-specific GABA antagonist completely abolished the hypnotic action of PGA in subconvulsive doses. Bicuculline (0.04 mg/kg) a GABAA antagonist, 3 mercaptopropionic acid (6 mg/kg) a GAD inhibitor at subconvulsive doses failed to neutralise the hypnotic action of PGA. On the other hand, PGA showed significant protection only against picrotoxin-induced convulsions, but was inactive against other convulsants tested. PGP which has no hypnotic activity, and has a mild anticonvulsant action in all the models except picrotoxin. A definite correlation was observed between the brain GABA and the hypnotic activity of PGA. However the present data indicate that the hypnotic and anticonvulsant activities are mediated probably through different brain GABA-ergic mechanisms. PMID- 1459631 TI - Evaluation of some newer non-steroidal anti-inflammatory indan-1-acids in various biological systems. AB - In line of the effort towards development of some newer indanyl non-steroidal anti-inflammatory agents and providing comprehensive SAR among this class of compounds some significantly active derivatives with low ulcerogenic potential were identified. Dealing with various long chain and branched chain compounds among this series, 3-(5, 6-dimethoxy indan-1-yl) propionic acid, 2-(5, 6 dimethoxy indan-1-yl) propionic acid and 3-(6-methoxy indan-1-yl) propionic acid were observed to have encouraging biological activity. Screening in various animal models of inflammation suggests their longer duration of action and lower ulcerogenic liability. PMID- 1459632 TI - Mechanism of anti-stress activity of Ocimum sanctum Linn, eugenol and Tinospora malabarica in experimental animals. AB - Effects of restraint stress (RS) and its modulation by O. sanctum (Os), eugenol and T. malabarica (Tm) were evaluated on some biochemical and biophysical parameters in rats. RS induced elevations in blood glucose and urea levels, were unaffected by either Os, eugenol or Tm pretreatment. However, both Os and eugenol lowered RS-induced cholesterol levels. RS also caused a generalized increase in enzyme activity and Os, eugenol or Tm effectively lowered the RS-induced elevations in lactate dehydrogenase (LDH) and alkaline phosphatase. RS also induced (a) increased membrane protein clusterization, (b) increased membrane fluidity and (c) reduced membrane thickness--in RBC membrane, whereas, the effects on the synaptosomal membrane were less marked. The RS-induced changes in RBC membrane dynamics were attenuated/reversed by Os, eugenol or Tm, in a differential manner. These biochemical and membrane changes during Rs and their modulation by the adaptogens are discussed in light of the possible mechanisms of action of these agents, during such aversive stimuli. PMID- 1459633 TI - Effect of cadmium on tissue glutathione and glutathione peroxidase in rats: influence of selenium supplementation. AB - Administration of cadmium (2.5 mg/kg, sc on alternate days for 3 weeks) to male albino rats led to significant accumulation of cadmium and metallothionein in the liver and kidneys. The activity of glutathione peroxidase was significantly decreased whereas, the concentration of glutathione was increased in these organs. Glycine-l-14C incorporation studies showed enhanced synthesis of glutathione in kidney but not in the liver. Selenium supplementation (1 mg/kg/day orally) failed to prevent these cadmium-induced changes, although it resulted in very high accumulation of selenium in these organs indicating the formation of cadmium-selenium complex. PMID- 1459634 TI - Experimental pathogenicity of Mollicutes of bovine udder origin in hamster tracheal ring organ culture. AB - Hamster tracheal-ring organ culture was employed to examine pathogenic effects of 8 isolates of Mollicutes of bovine udder origin. The tested Mollicutes could be categorized into two groups: (i) Mycoplasma F-38, M. mycoides var. capri, M. bovigenitalium mixed with M. bovirhinis, and M. bovigenitalium mixed with M. bovirhinis and Mycoplasma F-38 produced significant ciliostatic effect and infiltration of neutrophils and lymphocytes in lamina propria/subepithelium, hyperplasia and desquamation of epithelial lining cells and loss of cilia; and (ii) A. laidlawii, A. axanthum, an unidentified Acholeplasma and a mixed isolate of M. bovis, M. bovigenitalium, Mycoplasma F-38 and A. laidlawii showed insignificant ciliostatic effects and produced mild histopathological lesions. This correlates with the disease causing potentials of the strains. PMID- 1459635 TI - Cardioprotective effect of cromakalim (potassium channel opener) in isoproterenol induced myocardial infarction in rats. AB - Animals pretreated with cromakalim (1 mg/kg,po) along with isoproterenol (85 mg/kg,sc) showed less myocardial degenerative changes on histopathological examinations when compared with those treated with isoproterenol alone. Cromakalim's beneficial effects on myocardium were in dose-dependent manner. Administration of cromakalim (po) lowered significantly the serum LDH and SGOT and depleted intracytoplasmic glycogen as demonstrated by periodic schiff staining procedure. Increase in blood clotting time was highly significant (P less than 0.001). The results suggest cardioprotective effect of cromakalim in isoproterenol induced myocardial infarction. PMID- 1459636 TI - Effect of doxorubicin on heart mitochondrial enzymes in rats: a protective role for alpha-tocopherol. AB - Effect of doxorubicin on heart mitochondrial enzymes was studied in rats with or without the administration of alpha-tocopherol. Rats were treated with doxorubicin 2.5 mg/kg, ip body wt once a week for 8 weeks. Alpha-tocopherol was co-administered orally for 2 months (400 mg/kg body wt daily). TCA cycle enzyme, NADH-dehydrogenase, cytochrome-C-oxidase and Na+,K(+)-ATPase activities were found to be decreased in doxorubicin treatment. A significant decrease in protease activity was observed with a concomitant increase in mitochondrial protein level. Mitochondrial lipid peroxide level was found to be increased with a decrease in thiol content. Alpha-tocopherol co-administration was found to maintain the mitochondrial enzyme activities as well as the thiol content. The results are discussed with reference to the antioxidant nature of alpha tocopherol. PMID- 1459637 TI - Effect of five-membered heterocycles against Leishmania donovani infection. AB - Impact of change of heteroatom in pentavalent heterocycles, viz., pyrroles, isoxazoles, imidazoles and crotonates on the profile of antileishmanial activity against amastigotes of L. donovani using in vivo test system and macrophage amastigote culture system has been studied. Sixty-three compounds were tested. Nine imidazoles showed marginal activity in vivo, whereas 3 out of 10 compounds of isoxazolone series and 2 out of 4 substituted aminocrotonates exhibited antileishmanial activity. Of the 30 substituted pyrroles, except 8 all showed antileishmanial activity in vivo on day 7 post treatment. PMID- 1459638 TI - Autoimmunity in amoebiasis. AB - Amoebic liver abscess (ALA) and symptomatic intestinal amoebiasis cases were assessed by indirect haemagglutination assay for auto-reactive IgG and IgA class of antibodies in response to healthy human serum IgG and IgA. The present results indicated the presence of autoreactive IgG and IgA class of antibodies in ALA and intestinal amoebiasis respectively. PMID- 1459639 TI - Bromocriptine-induced implantation failure in mice: failure of the stud male to protect pregnancy. AB - The presence of the stud male failed to prevent implantation failure in newly inseminated females induced by administration of bromocriptine. This is in contrast with the ability of the stud male to prevent implantation failure in females induced by alien male exposure, and nutritional stress. Since bromocriptine is a potent inhibitor of hypophysial prolactin release by virtue of its stimulatory effect on hypothalamic dopaminergic activity, the results suggest that the stud male-originating luteotrophic stimulus is incapable of overriding the dopaminergic activity in bromocriptine-treated females. PMID- 1459640 TI - Lung injury by amiodarone, an antiarrhythmic drug, in male rats. AB - Administration of single dose (175 mg/kg body wt) of amiodarone dissolved in water through gavage for 3 weeks damaged the lung and changed the content of lung lavage. Activities of bronchoalveolar lavage (BAL) angiotensin converting enzyme (ACE) and lactate dehydrogenase (LDH) increased significantly. Also, the protein and lactate content of the lavage fluid increased significantly over the control. The drug also produced marked changes in morphology of the lung of experimental animals. PMID- 1459641 TI - Cervix tumour cell line established from tumour after long term passages as heterotransplant in nude mice. AB - One human cancer of the uterine cervix xenograft was established in tissue culture only after repeated passages in nude mice suggesting that with the repeated passages in nude mice, tumour cells acquire some properties which allow them to grow in vitro. Attempts to establish cell line tumours from earlier passages were not successful. The established cell line is tumourigenic. On inoculation of cultured cells in nude mice tumour take was found to be 100%. Karyotypic analysis revealed human origin. PMID- 1459642 TI - Tissue changes induced by enterotoxic preparations of Salmonella weltevreden in ligated rabbit gut segments. AB - Culture filtrates and cell lysates of two strains of S. weltevreden which caused dilation of ligated rabbit gut segments (characteristic associated with the enterotoxic activity) induced mild to severe architectural changes in the test segments of intestine. The dilated segments contained thick, bloody and mucoid exudates. The results suggested that besides invasiveness and enterotoxigenicity, S. weltevreden possibly possessed factor (s) that damaged intestinal tissue and played part in the pathogenesis of Salmonella gastroenteritis. PMID- 1459643 TI - Cloning and nucleotide sequencing of sheep growth hormone cDNA. AB - cDNA was prepared from the mRNA isolated from sheep anterior pituitary glands. On cloning cDNA in E. coli, a clone coding full sequence of sheep pre-growth hormone was determined. The sequence for the sheep growth hormone (GH) is in agreement with the amino acid sequence of the protein determined previously except for the asparagine residue at position 99 rather than aspartic acid and the arginine residue at position 146 in place of threonine. The cDNA sequence presented is also in accordance with the genomic sequence for the sheep GH gene that has been reported. PMID- 1459644 TI - Effect of storage duration on cell cycle kinetics and yield of chromosomal aberrations in PHA-responsive human peripheral blood lymphocytes. AB - Phytohaemagglutinin (PHA)-responsive lymphocytes from human peripheral blood samples, either irradiated or un-irradiated, showed increased frequency of first division metaphase cells (detected by fluorescence plus Giemsa (FPG) staining) as a function of duration of storage. Irradiated and subsequently stored samples showed small but significant increase for the yield of dicentrics. The yield of aberrant metaphases and deletions (excess acentrics) remained unchanged. Increasing Bromodeoxyuridine (BrdU) concentrations slowed down the cell cycle progression but did not influence the yield of aberrations including that of dicentrics. PMID- 1459645 TI - Effects of hCG and PMSG on responsiveness of ovary during period of delayed ovulation in an Indian vespertilionid bat, Scotophilus heathi. AB - Both hCG and PMSG treatments given either individually or sequentially between September and early February failed to induce ovulation in S. heathi, though they produced high degree of ovarian stimulation. The treatments induced ovarian enlargement, intense hyperaemia, marked changes in interstitial cells (ICs) and development of several antral follicles and varying degrees of abnormality in oocyte of most of the antral follicles. The percentage of abnormal oocytes in the ovary following hCG or PMSG treatment was dose-dependent. PMID- 1459646 TI - Influence of different photoperiods on development of gonad, cloacal gland and circulating thyroid hormones in male Japanese quail Coturnix coturnix japonica. AB - One day old chicks of Japanese quail were exposed to different photoperiods (LD, 8:16, 13.5:10.5, 16:8 and LL) and observations (testes weight, cloacal gland size, body weight and circulating thyroxine and triiodothyronine) were taken at the age of 3, 5, 7, 9 and 16 weeks. Results indicate that immediate reproductive development occurred in birds exposed to long photoperiods (greater than 12 hr). Growth under LD 8:16, was not apparent till 7th week and by 16 weeks, degree of gonadal development was similar in all the birds, irrespective of photoperiodic treatment. Whereas body weight of the intermediate and long day (LD 13.5:10.5, 16:8 and LL) treated birds increased upto 5th week and remained constant thereafter. But the chicks maintained under short day length (LD 8:16), showed spontaneous increase till the end of the study and birds were much heavier compared to all other groups. Plasma T4 concentration increased with increasing age till 9th week and remained unaltered thereafter. On the other hand T3 level did not change till 7th week followed by a decline. It is suggested that the initiation and degree of gonadal growth in quail depends on the availability of daily photoperiod, until the achievement of full breeding condition. Peak level of T4 observed in 9 week old birds may be involved in the development of photorefractoriness at that age. PMID- 1459647 TI - Effect of divalent metal ions on soluble and membrane-bound alkaline phosphatase activity in suckling rat intestine. AB - EDTA treatment of intestinal brush border membranes (BBM) and epithelial cell supernatant completely inhibited alkaline phosphatase (AP) activity in suckling rat intestine. AP activity was fully regained upon dialysis of the preparations against Zn2+ and to a lesser extent against Co2+, Ca2+ and Mn2+ ions. Other metal ions (Cd2+ and Mg2+) tested were essentially ineffective in restoring the enzyme activity. Considerable differences were observed in kinetic characteristics of the membrane-bound and soluble AP activities in response to various metal ions. There were apparent differences in Km, Vmax, energy of activation (Ea) and thermal stability of the soluble and membrane-bound AP activities, after metal ion substitutions. Nearly 35% AP activity was solubilized on sodium dodecyl sulphate treatment of brush borders (membrane protein: detergent ratio 1:3; w/w). Dialysis of detergent solubilized BBM against different metal ions reconstituted AP activity in the particulate fraction: the order of effectiveness was Zn greater than Ca greater than Mn greater than Co. The kinetic properties of the reconstituted AP were essentially similar to the non-integrated enzyme activity in response to various divalent metal ions examined. But there were apparent differences in Km, Vmax, Ea and thermal stability of the reconstituted AP activity compared to native brush border enzyme. The results suggest the unique requirement of Zn ions for stability and catalytic activity of the soluble and membrane-bound AP activity in suckling rat intestine. PMID- 1459648 TI - Induction of tumour necrosis factor alpha in experimental animals treated with hepatotoxicants. AB - Administrations of hepatotoxicants namely carbon tetrachloride (CCl4:0.4 ml in 1.2 ml of liquid paraffin) and ANIT (1 ml of 1.5% solution in liquid paraffin) in Charles foster rats (force fed) and D-galactosamine (8 mg in water per swiss albino mouse, ip) induce the release of TNF-alpha in case of CCl4 and D galactosamine. High TNF-alpha level was observed up to 48 hr in CCl4 and up to 24 hr in D-galactosamine treated animals. Elevated levels of biochemical like ALP and SGPT are also recorded. TNF-alpha level can be measured of tissue damage and prognosis in case of hepatitis. PMID- 1459649 TI - Insecticide induced disruptions in functioning of developing brain of Rana cyanophlictis. AB - Synthetic pyrethroid insecticide permethrin significantly decreased the levels of regulatory proteins (S-100 and calmodulin) in the developing CNS of tadpoles of R. cyanophlictis. Remarkable inhibition of enzymes acetylcholinesterase and choline acetylase and significant accumulation of neurotransmitter acetylcholine were observed in permethrin treated animals. Permethrin exposure significantly decreased the activity of phosphodiesterase. The results support molecular disruptions occurring due to permethrin induced toxicity. This in turn may bring about neuronal inefficiency in the treated tadpoles. PMID- 1459650 TI - Effect of citrate feeding on free radical induced changes in experimental urolithiasis. AB - Feeding calculi producing diet (CPD) to rats for 4 weeks produced calcium oxaltate stones. Supplementation of sodium citrate to CPD (c-CPD) prevented stone formation. Except oxalate, the excretion of calcium, phosphorus and magnesium was restored to normal in c-CPD fed rats. The CPD fed rats exhibited increase in glycolic acid oxidase (GAO) and lactate dehydrogenase (LDH) activities and only GAO activity was partially restored in c-CPD fed rats. Kidney sub-cellular fractions of calculi producing diet (CPD) fed rats showed increased susceptibility for lipid peroxidation in presence of promotors. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase and glutathione peroxidase and antioxidant concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin E were significantly decreased while the xanthine oxidase activity, and concentrations of hydroxyl radical, diene conjugates and hydroperoxides were significantly increased in CPD fed rats. The susceptibility to lipid peroxidation, activities of antioxidant enzymes, and the concentration of antioxidants were not normalized by feeding citrate. PMID- 1459651 TI - Effect of picroliv on glutathione metabolism in liver and brain of Mastomys natalensis infected with Plasmodium berghei. AB - Administration of picroliv, the active principle from Picrorhiza kurrooa, at a dose of 6 mg/kg, po for two weeks showed significant protection against changes in liver and brain glutathione metabolism of Plasmodium berghei infected Mastomys natalensis. The depletion of reduced glutathione level and inhibition of glutathione-S-transferase, glutathione reductase and glutathione peroxidase activities due to P. berghei infection were markedly recovered by picroliv. The increased levels of lipid peroxidation products in damaged tissues were also reduced along with the recovery of glutathione metabolism. PMID- 1459652 TI - Effect of gossypol on tissue levels of glutathione and thiobarbituric acid reactive products in rats. AB - Gossypol was administered in pubertal and adult rats and lipid peroxide formation and GSH levels were estimated in different tissues like liver, testis, heart and kidney. Gossypol caused low generation of lipid peroxides, measured as thiobarbituric acid reactive products (TBAR), without causing significant changes in tissue glutathione (GSH) levels. This effect was more pronounced in liver and testis as compared to other tissues. In vitro effect of gossypol to inhibit lipid peroxidation as observed in vivo suggested that binding of gossypol to plasma membranes may result in inhibition of lipid peroxide generation. PMID- 1459653 TI - Elevation of C-reactive protein in serum of Channa punctatus as an indicator of water pollution. AB - Effect of some pollutants like heavy metals, non-metals and pesticides on the circulating level of C-reactive protein (CRP) which is an acute phase plasma protein was studied in a freshwater murrel C. punctatus. Fish was exposed to nonlethal doses of these xenobiotics which were apparently safe. But the level of CRP detected by sensitive single radial immunodiffusion (SRID) technique showed that within 12 hr of exposure the nonlethal doses of xenobiotics could initiate the acute phase response in terms of elevated CRP titre. Heavy metals caused the acute phase within 24 hr, nonmetals and Metacid-50 within 48 hr exposure. The carbamate compound, carbaryl demonstrated a biphasic response to CRP level which may be correlated with the reversible type of anticholinesterase property of this compound while Metacid-50 is an irreversible type of anticholinesterase agent. The assessment of the CRP level in the serum of fish may be utilized as a primary bioindicator of a contaminated environment toxic enough to mount an acute phase response. PMID- 1459654 TI - Hepatoprotective activity of Azadirachta indica leaves on paracetamol induced hepatic damage in rats. AB - Effect of A. indica leaf extract on serum enzyme levels (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, acid phosphatase and alkaline phosphatase) elevated by paracetamol in rats was studied with a view to observe any possible hepatoprotective effect of this plant. It was interesting to observe that serum enzyme levels were much elevated in paracetamol induced animals than in those receiving a combination of paracetamol and lead extract. It is stipulated that the extract treated group was protected from hepatic cell damage caused by paracetamol induction. The findings were further confirmed by histopathological study of liver. PMID- 1459655 TI - Role of pure and biologically active amoebal RNA in assessment of lymphokines: a report of 55 ALA cases. AB - Amoebic liver abscess cases (55) were assessed for release of lymphokines (LMIF) using pure and biologically active amoebal RNA of axenic Entamoeba histolytica (NIH: 200) obtained with cesium chloride centrifugation. Lymphokines released by T lymphocytes in response to both amoebal RNA and whole amoebic lysate (WAL) were tested by leukocyte migration inhibition test (LMIT) on blood samples from amoebic liver abscess cases. A significant increase was observed in the release of lymphokine and 100% positivity was observed with amoebal RNA compared to whole amoebic extract with a positivity of only 78%. The difference between means leukocyte migration inhibition of the above two with regards to release of lymphokine was highly significant (P less than 0.001). This shows that patients had high degree of leukocyte sensitization to amoebal RNA of E. histolytica compared to whole amoebic lysate. These findings suggest that the amoebal RNA plays an important role as a potent antigen in the elicitation of cell mediated immune responses in amoebic liver abscess cases. PMID- 1459656 TI - Disposition of norepinephrine and epinephrine in jejunum of WLH chicken. AB - Disposition of (-)-norepinephrine and (-)-epinephrine in jejunum of WLH chicken was studied using oil-immersion technique. The relative rate of different routes of disposition of catecholamines was in the following order: for (-)-NE COMT greater than or equal to MAO greater than or equal to U2 greater than U1, for (-) Epi U2 greater than or equal to COMT greater than MAO greater than U1. The role of enzymatic degradation is almost equal to that of uptake processes for (-)-Epi, but it was greater for (-)-NE. PMID- 1459657 TI - Relative ranking of culture media based on proliferation kinetics and spontaneous chromosomal aberrations in PHA-responsive human peripheral blood lymphocytes. AB - Proliferation kinetics and spontaneous yield of chromosomal aberrations phytohemagglutinin (PHA)-responsive peripheral blood lymphocytes were studied from blood samples collected from 45 individuals in 4 different synthetic media. Except for a significant difference for Eagle's MEM and RPMI 1640, the other media did not show difference for the yield of chromatid or chromosome type of aberrations. Differences were however noticed in the proliferation kinetics (mitotic and proliferative rate indices) of cells among the media used. The study indicated that (i) the intrinsic properties of media which influence proliferation rate and yield of chromosomal aberrations are independent of each other as higher proportion of first division cells do not correspond with higher frequency of chromosomal aberrations, (ii) the amount of free-radical scavengers present in the medium, apart from the genetic make-up of the individuals, may contribute to the spontaneous yield of chromosomal aberrations and (iii) RPMI 1640 medium, which showed higher transformation and faster cycling rate for the lymphocytes, may be considered as medium of choice for analysing two main cytogenetic end-points, chromosomal aberrations and sister chromatid exchanges (SCEs). PMID- 1459658 TI - Presence of RNA from yeast inhibits the photoreactivation of UV-irradiated DNA by Phr A photolyase from Escherichia coli. AB - Photoreactivation of UV-irradiated DSNA with phr A photolyase from Escherichia coli was studied in the presence of yeast RNA. Mixing of RNA with UV-irradiated DNA before its treatment with photolyase inhibited the photoreactivation of DNA. Denatured (by sonication) RNA was found to be more effective in blocking photolyase action. Agarose gel electrophoresis experiments suggest that this inhibition of photoreactivation is due to interference in the binding of photolyase with UV-irradiated DNA by yeast RNA. PMID- 1459659 TI - Cockroach in right main bronchus--an unusual foreign body. AB - Foreign body aspiration in children is not a uncommon clinical problem. Usually the foreign body is of vegetable origin. It is distinctly uncommon to find a living organism like cockroach, especially a large one as a foreign body in respiratory tract. Here we report one such rare experience. PMID- 1459660 TI - Cold abscess due to malignant pleural mesothelioma. AB - A middle aged male presented to us with a cold abscess on the left side of chest which later proved to be a malignant pleural mesothelioma. The clinical, radiological and histopathological findings have been discussed. PMID- 1459661 TI - Fracture of tracheostomy tubes--report of 3 cases. AB - Fracture of the tubes appears to be caused by their prolonged use and defective fusion at the junction of cannula and phalange. We report here three cases of fractured polyvinyl chloride tracheostomy tube, an unusual complication of tracheostomy, presenting as foreign body in the trachea. PMID- 1459662 TI - Farmer's lung disease in north-western India--a preliminary report. AB - A study of farmer's lung (FL) disease was carried out in 197 subjects engaged in farming and having respiratory complaints of varying duration. It revealed that 13.2% of the subjects had precipitating antibodies against thermophilic actinomycetes, with Faenia rectivirgula (Micropolyspora faeni) alone accounting for 85% of the positive reactions. Precipitating antibodies against Thermoactinomyces vulgaris and T. thalpophilus were observed only in 1.5% and 0.5% of the subjects, respectively. Two subjects concomitantly demonstrated F. rectivirgula and T. vulgaris-specific serum precipitins. Sixty (30%) of the subjects related their respiratory symptoms to exposure to wheat straw/thresher's dust or other vegetable substrata in the working environment. Based upon a suggestive clinical history, roentgenography, pulmonary function studies and demonstration of serum precipitins against F. rectivirgula, FL was diagnosed in 4 subjects whose salient features are presented and discussed. To the best of our knowledge, this is the first authentic report on FL from India. A comprehensive epidemiological survey is indicated to determine the prevalence of FL in different geo-climatic regions of the country. PMID- 1459663 TI - Evaluation of unguided transbronchial biopsy in the diagnosis of pulmonary disease--its safety and efficacy as an out-patient procedure. AB - Sixty-five patients underwent unguided fiberoptic transbronchial biopsy on an out patient basis. Satisfactory material for histopathological examination was obtained in 55 patients. A reasonably definite pathological diagnosis could be established in 51 patients. The commonest diagnosis arrived at was that of interstitial fibrosis. Complications were observed in 4 (6.2%) patients. Fiberoptic transbronchial biopsy is, therefore, a safe and efficacious out patient technique for establishing a pathological diagnosis in patients with infiltrative, diffuse or localized pulmonary disease. PMID- 1459664 TI - Intensive respiratory care service--our eight-year experience. AB - Intensive respiratory care service has come a long way from the beginning in Scandinavia in early 1952. Intensive care service (IRCU) was started at our institute in 1983 as tetanus and respiratory care ward which has developed into Department of respiratory diseases over years. We are reporting our experience of 886 cases of acute respiratory failure (ARF) treated from Jan, 1983 upto April 1990. PMID- 1459665 TI - Perfusion lung scan in tropical pulmonary eosinophilia. AB - Perfusion lung scan using macroaggregate of human serum albumin tagged with I131 was done in 7 patients with tropical pulmonary eosinophilia (TPE). In the 3 untreated patients perfusion defect of varying degree could be noticed, whereas in 4 other patients with history of chronic illness and previous treatment with multiple courses of diethylcarbamazine the lung scan was normal. Possible pathophysiology in light of above findings in TPE is discussed. PMID- 1459666 TI - Effect of growth on lung transfer factor and its components. AB - Measurement of lung transfer factor for CO (TLCO) and its constituent components, viz. diffusion capacity across alveolar capillary membrane (Dm) and instant pulmonary capillary blood volume (Vc) were undertaken in 120 healthy non-smoker males by single breath technique. All the three parameters (TLCO, Dm, Vc) showed direct negative correlation with age. While TLCO and Dm showed a significant direct positive correlation with height, there was no correlation between VC and height. The degree of correlation increased when both age and height were used together than either of them alone for prediction of TLCO120. The prediction formulae (TLCO120 = 3.8 + 21 H (m)-0.308 A) using both age and height has regression value (R) of 0.6479 (p < 0.001). PMID- 1459667 TI - Acute accidental exposure to chlorine fumes--a study of 82 cases. AB - Eighty-two patients were hospitalized following an accidental exposure to chlorine. All patients presented with dyspnoea and cough. The other symptoms included irritation of throat (53.6%), irritation of eyes (42.3%), headache (29.2%), abdominal pain (26.8%), vomiting (24.3%) and giddiness (9.7%). All of them had bronchospasm and 5 (6%) had cyanosis at the onset. An x-ray of the chest revealed patchy infiltrates in 3 (3.85%) and hilar congestion in 2 (2.44%). Pulmonary function tests showed an obstructive pattern in 27.4%, restrictive in 3.25% and mixed in 53.2%. Pulmonary functions were normal in 16.1% of the patients. Bronchoscopy revealed tracheobronchial mucosal congestion in all cases, hemorrhagic spots in 35.7%, erosions and ulcers in 12.5%. All patients were treated with oxygen, aminophylline, hydrocortisone and antibiotics. Haematemesis (n = 1) and pulmonary oedema (n = 2) developed 12 hours after the admission. Two other patients developed pneumonia 48 hours later. All patients recovered satisfactorily. On follow-up 16 patients had no sequelae after one year. Pulmonary functions were normal in 5 patients after 3 years of follow-up. PMID- 1459669 TI - Inhibition of acetylcholinesterase of mice erythrocytes & synaptosomes by dimethylsulfoxide. AB - In vitro inhibitory effect of dimethylsulfoxide (DMSO) on acetylcholinesterase of erythrocyte membranes and synaptosomes of mice was observed using acetylthiocholine as substrate. DMSO inhibited the enzyme from both sources and the effect was concentration dependent. It produced an inhibition of 26 to 28 per cent at a concentration of 0.13 mM and 92 to 95 per cent at a higher concentration of 1.91 mM. The Km of bound and solubilized enzyme of the synaptosomes was 0.2 and 0.15 mM while that of erythrocyte membranes 0.5 and 0.33 mM respectively. The Vmax was 0.4 and 0.4 (for synaptosomes) and 0.67 and 0.59 (for erythrocyte membranes) Mmoles/mg protein/min, respectively for bound and solubilized forms. The Ki of solubilized enzyme of synaptosomes was 0.11 mM. Kinetic studies showed that the inhibition was competitive in nature. PMID- 1459668 TI - Lung cancer in India--a perspective. AB - The epidemiology, aetiopathogenesis, diagnostic methods and management of lung cancer in India have been reviewed based on the published data from this country. Over the years, the incidence has been increasing and the disease is being recognized more often. Smoking is the most important aetiological factor. Beedi smoking which is a common practice in this country is equally, if not more, harmful than cigarette smoking in causing lung cancer. Tremendous improvement has been made in various diagnostic techniques. Cytological methods, fiberoptic bronchoscopy and percutaneous lung aspiration are being used more frequently. At the treatment front, although radiotherapy and chemotherapy are being used, the results are not very encouraging. Except in few cases, surgery is usually not feasible because of advanced disease. Prevention of lung cancer by anti-smoking measures should be the main goal of solving the problem in this country. PMID- 1459670 TI - Serum lipids & lipoprotein profiles of cigarette smokers & passive smokers. AB - Serum lipids and lipoproteins of 50 active and passive smokers were compared with levels in 25 control subjects. Active smoking resulted in an increase in total cholesterol (Tc) and triglycerides (Tg) as compared to control group. The passive smokers also showed relatively higher levels but the effect was not significant. Active smoking raised the low density lipoprotein cholesterol (LDLc) and very low density lipoprotein cholesterol (VLDLc) levels whereas high density lipoprotein cholesterol (HDLc) content was lowered, thus resulting in decreased ratios of HDLc/Tc and HDLc/LDLc. The passive smokers also showed slightly higher levels of LDLc and VLDLc but lower levels of HDLc, and a lower HDLc/LDLc ratio. Our findings suggest that smoking alters the serum lipids and lipoproteins and these changes are related to the duration and amount of smoking. PMID- 1459671 TI - Effect on curcumin on cholesterol gall-stone induction in mice. AB - A study was carried out on the efficacy of curcumin in reducing the incidence of cholesterol gall-stones (CGS), induced by feeding a lithogenic diet in young male mice. Feeding a lithogenic diet supplemented with 0.5 per cent curcumin for 10 wk reduced the incidence of gall-stone formation to 26 per cent, as compared to 100 per cent incidence in the group fed with lithogenic diet alone. Biliary cholesterol concentration was also significantly reduced by curcumin feeding. The lithogenic index which was 1.09 in the cholesterol fed group was reduced to 0.43 in the 0.5 per cent curcumin supplemented group. Further, the cholesterol: phospholipid (C/PL) ratio of bile was also reduced significantly when 0.5 per cent curcumin supplemented diet was fed. A dose-response study with 0.2, 0.5 and 1.0 per cent curcumin supplemented lithogenic diets showed that 0.5 per cent curcumin was more effective than a diet with 0.2 or 1 per cent curcumin. PMID- 1459672 TI - Effect of three antibacterial drugs in lowering blood & stool ammonia production in hepatic encephalopathy. AB - Neomycin (700 mg/8 h), ampicillin (500/6 h) and metronidazole (400 mg/8 h), were compared for their effect, on oral administration for 4 days, in reducing blood ammonia in 27 patients with stable chronic liver disease. It was found that there was 38.2, 38.5 and 8.7 m mol/litre mean reduction in blood ammonia in the neomycin, ampicillin and metronidazole treated groups respectively. The difference in blood ammonia was statistically significant for both neomycin (P = 0.01) and ampicillin (P = 0.03) but there was no significant change after metronidazole treatment (P = 0.6). The total stool enzyme activity at optimum pH was maximally reduced by ampicillin and minimally with metronidazole. The reduction was noted to be 3.51 m mol/1 (P = 0.01), 3.87 m mol/1 (P = 0.08) and 2.8 m mol/1 (P = 0.02) of NH3/g dry weight of stool for neomycin, ampicillin and metronidazole respectively. The main bacterial gut enzymes responsible for ammonia production, urease and protease, were found to be very sensitive to stool pH. At pH 6 their activity was around 20 per cent of what was found in optimum pH of 7.4 and at pH 5 it is only about 8 per cent of optimum activity. None of the three antibacterial agents changed the stool pH significantly. It can be concluded that oral neomycin and ampicillin are superior to oral metronidazole in lowering blood ammonia. PMID- 1459673 TI - Detection of gene deletion in patients of Duchenne muscular dystrophy/Becker muscular dystrophy using polymerase chain reaction. AB - Polymerase chain reaction (PCR) was used to study the presence of gene deletion (the most prominent type of mutations) in some families afflicted by Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD). The results clearly demonstrate deletion in the central part of the DMD gene in two of the three families studied. This information can be useful for genetic counselling with particular reference to prenatal diagnosis and carrier analysis. PMID- 1459675 TI - Indian Council of Medical Research. Eight decades of progress (1911-1991). PMID- 1459674 TI - Induction of sister chromatid exchanges in phenytoin treated & untreated patients with epilepsy. AB - The mutagenic potential of phenytoin (PHT) was studied using the sister chromatid exchange (SCE) assay. Twenty nine PHT treated epileptics, 32 untreated and 32 normal healthy controls were analysed. Similar SCE frequencies were observed in untreated patients and patients on PHT monotherapy. Both groups had significantly increased SCE frequency as compared to controls. No positive correlation of SCE frequency with sex and duration of therapy was observed. The results of the present study suggest the role of the disease condition in inducing genetic damage as assessed by increased SCE frequencies. PMID- 1459676 TI - Communication with mothers--key to child survival. PMID- 1459677 TI - Perinatal mortality in Ludhiana, Punjab--a seven year hospital study. AB - Perinatal deaths occurring over a seven year period were studied in a teaching hospital in Punjab. Causes of death were analysed as per Wigglesworth's classification. We have further modified this by correlating different gestations and weight groups with causes of death. The perinatal mortality rate (PNMR) in the present study was 74/1000 and showed a downward trend secondary to a statistically significant fall of early neonatal mortality. There was a decline in PNMR among babies of 1500-2000 g. birth weight and 33-36 weeks gestation. Asphyxia and macerated still births were found to be the two main causes of death. Macerated still births were seen more commonly among babies of lower weight at all gestations. The PNMR of babies born to booked mothers was 22/1000 as compared to 152/1000 among unbooked mothers. It was concluded that to bring down the PNMR, economic development alone is not enough. Provision of adequate antenatal care to all mothers, health education and timely referral of high risk mothers is very essential. PMID- 1459678 TI - Socio-biological factors in underfive deaths in a rural area. AB - In 1985-86, 286 underfive deaths occurred among a population of 30,000 in a rural area of Haryana. Two hundred and eighty one were analysed for socio-biological factors related to under five mortality. Females had a higher mortality. About 2/3 of the deaths were in infants, and 90% in first 3 years. Most of the deaths (94%) occurred in the village itself, 58.4% did not seek any medical care during the terminal illness, 80-90% did not receive even a single dose of BCG, DPT or O.P.V., and 36.7% died in the first attack of illness. Though 68% had at least one episode earlier, 31.0% had been admitted in hospitals for an earlier episode of illness. In 42.8% of deaths, the birth order was IV or above. Deaths in socially and economically disadvantaged cases constituted 77.6%. The triad of diarrhea, ARI and malnutrition claimed 56% deaths. In 93% of the deaths, the mothers were illiterate and 96.4% were house wives. There was a sibling death earlier in the family in 78.3%, and 60.1% deaths were of those living in poor housing conditions. About 50% had radio for communication, 85.8% had bicycle for conveyance, and in 66.9% the family had piped water supply. All these findings have been discussed in the study. PMID- 1459679 TI - Infant feeding practices in rural Bangladesh. AB - A longitudinal study was done on the infant feeding practices in a rural area. One hundred and ten infants were followed up from birth to 1 year of age by alternate day home visits, to inquire about the type of food, and frequency of consuming it. It was found that 100% mothers breast-fed their infants from birth to 1 year, almost every day. But, bottles containing various kinds of milk and starchy food were added to 60% of infants diets by 3 months, and 80% by 5 months of age. This additional food was given mostly in diluted form, which was more so in case of tinned milk. Family food such as rice and vegetables were given in 30% and 40% child days respectively from 6 months to 1 year. Rural people withhold protein food and fruits during infancy. It is concluded, that infant feeding practices in our population is improper and mothers should, therefore, be trained and motivated on weaning practices for timely and adequate supplementation to ameliorate the presently observed dietary deficiency and early malnutrition in rural Bangladesh. PMID- 1459680 TI - Severity of rheumatic mitral regurgitation. AB - Thirty patients below the age of 15 years (range 8-1/2 to 15 years, mean 11.8 years) have been studied for the severity of rheumatic mitral regurgitation. Moderately severe to severe pulmonary venous hypertension was found in 76.6% and pulmonary arterial hypertension in 60%. Left ventricular volumes could be calculated in 13 patients. The end-diastolic volume was elevated in 11 and the endsystolic volume in 12 cases. The regurgitant fraction, calculated in nine patients was 0.6 or more in seven cases. The clinical and hemodynamic severity of mitral regurgitation in children was identical to that seen in adults in the absence of active rheumatic carditis. Children with dominant rheumatic mitral regurgitation can develop congestive failure on the basis of valvar damage per se. PMID- 1459681 TI - Prevalence of iodine deficiency disorders in adolescents. AB - In the present study the iodine status of 300 adolescent boys and girls was assessed by clinical examination and biochemical tests. The clinical examination revealed the total goitre rate (TGR) to be 65.2% among boys, and 69.6% among girls. The visible goitre rate (VGR) was 17.7% among boys and 21.1% among girls. Nutritional status of all adolescents was found to be poor as compared to their well-nourished counterparts. Using discriminant analysis it was found that age, height and weight of the adolescents were significantly related to goitre grade (p < 0.001), and they are important in prediction of goitre. Mild and moderate iodine deficiency were found to be prevalent among the adolescents. On the basis of urinary iodine/creatinine ratio, 38% of the adolescents were found to be suffering from mild iodine deficiency, i.e. average urinary iodine excretion between 50-100 mcg iodine/g creatinine. Moderate iodine deficiency (< 50 mcg iodine/g creatinine) was found to be prevalent among 12.4% of the adolescents. The results of this study indicate a high prevalence of mild and moderate IDD among the adolescents studied. PMID- 1459683 TI - Electrical response audiometry (ERA) in infants. AB - The electric response audiometry is a useful diagnostic technique for identifying hearing loss in infants. Among the various electrical responses, the BSER enables us to arrive at an accurate early clinical diagnosis of hearing loss in infants so that effective auditory input, which is the prime requisite for the conceptual foundation for the growth of communication, can be provided through appropriate intervention programmes. The electric response audiometry provides information regarding the physiologic state of the peripheral organs and auditory pathways but however, cannot ascertain whether the infant can hear, in terms of perceiving auditory information. Inspite of this major limitation, the growing acceptance of brainstem electrical potentials in clinics and laboratories throughout the world attests to their increasing importance especially in the assessment of hearing sensitivity of infants. PMID- 1459682 TI - Acute laryngeal stridor--controversies in current management. PMID- 1459684 TI - Evaluation of a deaf child. AB - One should be aware that the measurement of hearing is really an evaluation of a child's behavioural responses in a controlled setting to the presentation of various acoustic stimuli. The determination of hearing loss in some children is an ongoing process and may require more than one test session. Difficult to test children should be evaluated with as many techniques as possible for accurate cross checking of test results. Flexibility, patience and understanding and persistence are the watch words of successful hearing testing with children. For the bulk of patients who require audiological assessment however, the test battery (BOA, IMPEDANCE & BSER) approach seems to be the best available present day approach coupled with long term follow ups and careful management. PMID- 1459685 TI - Speech disorders in children. PMID- 1459687 TI - Cleidocranial dysplasia: underdiagnosed and misdiagnosed? PMID- 1459686 TI - Congenital malformations of the ear. PMID- 1459688 TI - Acro-osteolysis of phalanges in a case of cystic fibrosis. PMID- 1459689 TI - Family outbreak of scalp phthiriasis. PMID- 1459690 TI - Should cow milk be diluted for young infants. PMID- 1459691 TI - Neonatal uterine prolapse. PMID- 1459692 TI - Peripheral exchange transfusions. PMID- 1459693 TI - Acquired malaria--how early can it occur. PMID- 1459694 TI - Effects of interleukin-1 beta and tumor necrosis factor-alpha on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro. AB - Osteoblasts play a pivotal role during the bioresponse of bone to agents that stimulate bone resorption and/or inhibit bone formation including hormones, polypeptide growth factors, and cytokines. We examined the cytokines interleukin 1-beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) for their effects on osteoblastic proliferation and development and expression of alkaline phosphate and the osteoblast-specific protein osteocalcin in a mineralizing environment. Primary rat osteoblast-like cells (ROB) and osteoblastic cell lines derived from rat (ROS 17/2.8) and human (MG-63) osteosarcomas were studied. IL-1 beta and TNF-alpha were chosen because of their critical importance during the host response to local inflammatory stimuli. Qualitatively similar two- to threefold inhibition of osteocalcin synthesis by IL-1 beta and TNF-alpha were observed in all three postconfluent bone-forming model systems. Because of the readily measurable concentrations of osteocalcin produced in our culture protocol, it was not necessary to enhance osteoblastic synthesis of osteocalcin by supplementation with 1,25(OH)2-vitamin D3, a treatment which exerts pleiotropic effects on osteoblasts. Under the constraints of our protocol, where alkaline phosphatase and mineralization were already elevated at the 14-day onset of treatment, neither of these phenotypic properties was sensitive to a three-day cytokine exposure. Differences were noted in proliferation, where only TNF-alpha stimulated DNA synthesis in ROB cells, while both cytokines stimulated MG-63 cells. IL-1 beta and TNF-alpha failed to alter ROS 17/2.8 DNA synthesis except at the highest doses (25 pM IL-1 beta and 1 nM TNF-alpha) where inhibition was observed. These results further support the view that cytokine-mediated osteoblastic regulation can be relatively selective. PMID- 1459695 TI - Adhesive effect of certain cytokines and other perturbants on human neutrophils. AB - Pretreatment of normal human neutrophils with certain cytokines and other mediators caused some of the cells to become adhesive and stick to the plastic (polypropylene) incubation tubes during pretreatment and during the assay for phagocytosis of C3b.IgG-coated microspheres. Often as much as 40% of the cells were adherent to the tubes after the reaction. This sticking of the neutrophils to the plastic tubes was confirmed by increase in cytometer sipping time and by lactic dehydrogenase assay of the suspended cells and of the cells stuck on the sides of the empty incubation tubes. Only those perturbants that caused an up regulation of C3b receptors (CR1, CD35) and in most cases caused an enhancement of phagocytosis mediated the adhesiveness of the cells. Unless these stuck cells were detached by vigorous flushing with cold buffer containing EDTA, many of the cells were not admitted into the cytometer for determination of the effect of the perturbants on binding and phagocytic capacity of the neutrophils. This observation could have implications regarding the possibility of subpopulations of neutrophils and differences in function of adherent cells versus cells in suspension. In the cases studied there was no appreciable difference between the total binding and phagocytic capacities of the adherent and suspended cells. PMID- 1459696 TI - Changes in serum glycoprotein glycosylation during experimental inflammation in mice are general, unrelated to protein type, and opposite changes in man and rat: studies on mouse serum alpha 1-acid glycoprotein, alpha 1-esterase, and alpha 1 protease inhibitor. AB - Using the method of crossed affinity immunoelectrophoresis with concanavalin A in combination with digital image processing, unrelated serum glycoproteins from normal mice and from mice undergoing an experimentally induced inflammation were analyzed for their carbohydrate-derived microheterogeneity profile. This profile changed in a generalized way in mouse serum samples taken at various time intervals after the initial induction of inflammation. The changes are not related to the acute-phase behavior of the protein itself (be it positive, negative, or nonreacting), and they are opposite to the changes in microheterogeneity profiles reported previously for glycoproteins during the acute phase in human and rat sera. These findings are discussed in the context of the biosynthetic control of glycoprotein glycosylation during the acute-phase response. PMID- 1459697 TI - Loose stools in the early neonatal period. AB - During a two-year period, the various factors associated with loose stools in the early neonatal period were studied among hospital born babies. Low birth weight babies had a lower incidence of non-infective loose stools when compared to neonates with a birth weight of more than 2500 g (p < 0.001). Newborns delivered by Cesarean section (p < 0.001) and those born to women with more than two children (p < 0.02) had a greater frequency of loose stools. Initiation of supplementary feeding and administration of antibiotics were important factors in causing loose stools. Bacterial etiology could be found only in 9.3% of newborns having loose stools. A later onset of loose stools was noted in those, whose stool culture grew bacterial organisms. Only nine newborns with loose stools required antibiotic therapy. Although loose stools were less common among low birth weight babies, they often required treatment with antimicrobials. None of them developed any complications. Since majority of them are non-bacterial and non-infective, great caution must be exercised before administering antibiotics to newborns with loose stools. PMID- 1459698 TI - Congenital adrenal hyperplasia: experience at Calcutta. AB - Eight patients (7 females, 1 male) with congenital adrenal hyperplasia (CAH), were seen over a 24-month period beginning from March 1988. Seven patients had 21 hydroxylase (21-OH) deficiency while one had 11 beta hydroxylase deficiency. Of the 7 patients with 21-OH deficiency, 3 were of the salt losing (SL-CAH), and 4 were of the non-salt losing (NSL-CAH) type. The patients with NSL-CAH were diagnosed by their elevated 17-hydroxyprogesterone (17-OHP) levels. The 3 cases with SL-CAH were diagnosed on the basis of ambiguous external genitalia, typical electrolyte picture, normal female internal genitalia, sex chromatin and response to steroids. In one patient post-ACTH 17 OHP was alter measured. All 3 patients with SL-CAH were assigned the male sex. Sex reassignment was advised for two children; one accepted the advice and the child is doing well; one family did not accept sex reassignment and the child died. One patient died due to non availability of fludrocortisone. Six patients are under follow-up. All are doing well except one patient with NSL-CAH who started treatment late. We conclude that a high index of suspicion, early diagnosis and meticulous patient education are the key features of successful management of CAH in India. PMID- 1459699 TI - Perinatal hypophosphatasia. PMID- 1459700 TI - Neonatal adrenal hemorrhage. PMID- 1459701 TI - Acute glomerulonephritis in multi-drug resistant Salmonella typhi infection. PMID- 1459702 TI - Parapharyngeal abscess: an unusual complication of measles. PMID- 1459703 TI - Unusual presentation of tuberculous peritonitis. PMID- 1459704 TI - Congenital sensory neuropathy with anhidrosis. PMID- 1459705 TI - Priapism in children with sickle-cell disease. PMID- 1459706 TI - Hereditary retinal-renal dysplasia. PMID- 1459707 TI - Cerebellar syndrome in malaria. PMID- 1459708 TI - Antithymocyte globulin in aplastic anemia. PMID- 1459709 TI - A satellited metacentric marker chromosome in a phenotypically normal male (transsexual). PMID- 1459710 TI - Celphos poisoning. PMID- 1459711 TI - Neglected foreign body larynx. PMID- 1459712 TI - Irrational use of oral rehydration solutions. PMID- 1459713 TI - Aminoglycoside nephrotoxicity in clinical practice. PMID- 1459714 TI - BCG test in diagnosis of tuberculosis. PMID- 1459715 TI - Bacteriological examination of pharyngeal secretions. PMID- 1459716 TI - Breast feeding and infant growth. PMID- 1459717 TI - Nutritional disorders in adolescent girls. AB - Four hundred and fifty four adolescent girls (11-18 years) were screened for nutritional disorders by anthropometry (weight, height and triceps skinfold measurements), clinical examination and hemoglobin estimation. Of these, 56% belonged to high socio-economic groups (Group A) and the rest (44%) to lower middle class (Group B). A large number of girls from Group B were undernourished (35.5% had weight/height2 less than the fifth percentile of reference standard) stressing the need for nutritional screening, nutrition and health education. Obesity was prevalent in 3.1% of Group A adolescents. Goitre grade I or more was observed in a high proportion of Group B girls, stressing the need for continued consumption of iodized salt in Delhi. Anemia appears to be a major health problem in adolescent girls in both groups (47, 56% in Groups A and B, respectively) underlying the ned for iron supplementation along with health education. PMID- 1459718 TI - Per rectal diazepam therapy in convulsive disorders. AB - One hundred and twenty children with persistent convulsions (lasting > or = 10 min) were treated with per rectal diazepam (dosage: 0.2 to 0.7 mg/kg/dose). Another group of 100 age matched children with convulsions, along with those who did not respond to rectal therapy were given intravenous diazepam in a dosage of 0.2 to 0.3 mg/kg/dose. Rectal treatment was effective in 80.83% cases while intravenous diazepam was effective in 90% cases which is statistically just significant (p < 0.05). No significant difference was observed in the efficacy of two routes of administration in controlling convulsions of different clinical types and various etiological groups (p < 0.05), except for primary generalized type where intravenous route was more effective than the rectal one (p < 0.05). No significant side-effect was observed with rectal therapy. Among the 23 (19.17%) children in whom rectal therapy failed, 12 (10%) responded to intravenous diazepam while the remaining 11 (9.17%) cases were resistant to both routes of administration. PMID- 1459719 TI - Kerosene oil poisoning--a childhood menace. AB - This study documents 3-year retrospective analysis of accidental kerosene oil poisoning in 70 children with regard to clinical profile, radiological changes and outcome. About 77% of cases were between 1 and 3 years old. Fifty children (71.4%) developed significant symptoms, with onset soon after to within 10 hours of ingestion. These included breathlessness (55.7%), fever (47.1%), cough (31.4%), restlessness (25.7%) and abdominal distension (15.7%). Chest X-rays were obtained in 65 children. Abnormal radiographs were seen in 45 (69.2%) children with right basal infiltrates being the commonest picture (21.4%). Ingestion of more than one ounce of kerosene oil adversely affected the clinical and radiological profile. Severely malnourished children had extensive radiological changes and poorer clinical outcome. One case developed myocarditis, a complication which has not been reported to the best of our knowledge. Mortality rate was 4.3%. All deaths occurred within 48 hours of admission. PMID- 1459720 TI - Psychosocial study of leukemic children and their parents. AB - Psychosocial assessment was carried out in 35 children with acute lymphatic leukemic, an equal number with non-leukemic chronic illness and their parents. Psychological dysfunction existed more frequently in parents of leukemic children. Depression as an initial reaction on being conveyed the diagnosis, was seen in 85.8% whilst anger was observed in 42.8%. Majority (89.7%) entertained doubts about whether a correct diagnosis has been established. Understanding of the disease, its possible course and the need for prolonged treatment, was appreciated by about 65.7% of parents. The disease imposed serious social, financial and occupational burdens on the family. Measures used to cope with such stresses included meeting close friends and relatives and finding solace in religious activities. When comparing psychopathology in leukemic children with that in chronically ill non-leukemic counterparts, significant differences were observed in certain specific syndrome scores. Conduct disorder, anxiety, depression and psychotic symptoms were more prevalent in leukemic children. This study emphasizes the necessity of active psychosocial intervention in the total care of childhood leukemia. PMID- 1459721 TI - Cerebral palsy. AB - The clinical pattern and etiology of 544 cases of cerebral palsy were studied retrospectively. Of these cases, 354 (65.1%) were males. Four hundred and ninety seven (91.4%) cases were of spastic type. Hypotonic, ataxic and athetoid cerebral palsy were observed in 5.5, 1.5 and 1.3% cases, respectively. There was one case each of tremor and mixed type. In the spastic group, quadriplegia comprised the maximum number of cases (34.9%). Hemiplegia (28.7%) and diplegia (21.9) were also common. Mental retardation was found in 47.2%, while speech impairment was observed in 37% cases. Other handicaps included visual (9%), seizures (8.8%), and auditory handicap (2.9%). The etiological factors were prenatal in 7.7% cases, natal in 43.8% cases and postnatal in 26.1% cases. More than one etiological factor was observed in 14.5% cases, while in 7.9% cases, no apparent cause could be found. PMID- 1459722 TI - Thyroid dysfunction in multi-transfused iron loaded thalassemia patients. AB - Seventy-two transfusion-dependent iron loaded thalassemia patients were investigated for thyroid dysfunction by estimating circulating thyroid hormones (T4 and T3) and basal thyroid stimulating hormone (TSH). They were also evaluated for their liver function (biochemically) and iron overload by estimating serum ferritin. Thyroid failure (hypothyroidism) was documented in 14 patients (19.4%). In all, 3 groups were seen, i.e. Group 1: Normal T4, T3, TSH (58 patients: 80.6%); Group 2: Compensated hypothyroidism characterized by normal T4, T3 and raised TSH (9 patients: 12.5%); Group 3: Decompensated hypothyroidism characterized by decreased T4 and increased TSH (5 patients: 6.9%). Interestingly, impaired thyroid function could not be correlated with age, amount of blood transfused, liver dysfunction or degree of iron overload. It is postulated that an inter-play between chronic hypoxia, liver dysfunction and iron overload may be responsible for the thyroid damage. PMID- 1459723 TI - Smoking-related DNA adducts in human gastric cancers. AB - DNA was extracted from the tumour tissue of 26 patients (18 smokers, 8 non smokers) undergoing surgery for gastric cancer, and analyzed for the presence of DNA adducts by the 32P-post-labelling method. Adducts were detected in all samples tested, and adduct levels ranged from 2 adducts/10(8) nucleotides to 60 adducts/10(8) nucleotides. In male subjects, adduct levels were significantly greater in the DNA of smokers than in that of non-smokers. These results support epidemiological data suggesting that smoking is a risk factor for gastric cancer. PMID- 1459724 TI - Cell kinetics evaluation of colorectal tumors after in vivo administration of bromodeoxyuridine. AB - Although several biomarkers have been tested, Dukes' (or TNM) stage at diagnosis is still considered the only prognostic factor of clinical relevance in colorectal cancer. Among the various biomarkers, the fraction of cells engaged in DNA synthesis has been extensively investigated as an indicator of tumor aggressiveness. Bromodeoxyuridine (BUdR) is a non-radioactive thymidine analogue which is incorporated into DNA during the S-phase of cycling cells. In order to evaluate the relationships between cell kinetics and morphologic variables, 500 mg of BUdR were given i.v. to 46 patients with colorectal cancer prior to surgery. After operation, a large tumor sample was taken and processed for immunohistochemical detection of BUdR-labeled cells in various regions of the neoplasm and in normal colorectal mucosa. Smaller superficial tumor specimens were also incubated with 3H-thymidine (3H-TdR) for the autoradiographic identification of labeled cells. In the 43 evaluable tumors, the overall BUdR labeling index (BLI, percent of labeled cells) was significantly higher in carcinoma (20.30 +/- 0.86%, SEM) than in normal colonic mucosa (6.51 +/- 0.49%). BLIs in central and peripheral regions of carcinoma were closely correlated (r = 0.48, p = 0.003). In 21 neoplasms a high correlation between overall BUdR and 3H TdR labeling index in the same tumor was observed (r = 0.57, p = 0.007). No evident association between overall BLI and clinical or morphologic parameters of the tumor was seen, including number of capillaries and ras-p21 protein expression. We conclude that BUdR immunostaining after in vivo administration of BUdR is a simple method for studying cell kinetics in various regions of colorectal cancer. BUdR labeling data are comparable to those obtained with in vitro incorporation of 3H-TdR. PMID- 1459725 TI - EGF receptor expression in primary laryngeal cancer: correlation with clinico pathological features and prognostic significance. AB - Epidermal-growth-factor-receptor(EGFR) expression was evaluated in 103 primary laryngeal tumors and in 42 normal laryngeal tissue specimens. Significantly higher EGFR levels were found in cancer specimens than in normal mucosa (p = 0.0053). EGFR expression did not correlate with age, tumor localization, T classification, cervical-lymph-node involvement or type of surgery, whereas it was higher in poorly differentiated tumors (G3) than in well/moderately differentiated (G1-G2) tumors (p < 0.05). Follow-up data were available for 74 patients. When EGFR status and the most important clinico-pathological characteristics were submitted to univariate analysis, tumor localization, type of surgery and EGFR status were found to be significantly correlated with disease free survival. The 24-month disease-free survival rate was 58% for EGFR+ cancer patients and 82% for EGFR- ones. With multivariate analysis, only EGFR status and tumor localization were identified as significant independent prognostic parameters. Data reported here suggest that high EGFR levels may identify a sub set of laryngeal-cancer patients with a particularly unfavorable prognosis. PMID- 1459726 TI - The p53 tumor-suppressor gene and ras oncogene mutations in oral squamous-cell carcinoma. AB - The frequencies of mutations in the p53 tumor-suppressor gene and ras proto oncogenes were investigated systematically in surgically resected oral squamous cell carcinomas (SCCs) using single-strand conformation polymorphism (SSCP) and/or dot-blot hybridization analysis of DNA fragments which had been amplified by the polymerase chain reaction (PCR). p53 gene mutations, within the region of exons 5 to 8, were detected in 17 out of 27 (63%) tumor specimens. The role of p53 mutations in cell-line establishment was investigated. p53 gene mutations were detected in 5 out of 6 tissue samples from which cell lines were established and in 4 out of 5 specimens from which cell lines could not be established, suggesting that the presence of p53 gene mutations is not by itself sufficient for cell-line establishment. Tumor samples were also analyzed for point mutational activation of the ras proto-oncogenes. One out of 30 (3%) tumors showed an activating point mutation in codon 12 of H-ras, this being consistent with reports from Europe and USA but not with any from India. Compared to frequencies of the other genetic changes so far reported for oral SCC, the p53 mutations have been observed most often to undergo genetic change. p53 gene mutation is thus intimately involved in the genesis of oral SCC and consequently should be useful as a marker for the diagnosis of this neoplasm. PMID- 1459727 TI - Prognostic relevance of serum hyaluronan levels in patients with breast cancer. AB - The serum hyaluronan (HA) level of 238 women with breast cancer was measured by means of a specific radiometric assay. The results show no significant increase in serum HA when compared to levels in 120 control sera. A number of prognostic factors were evaluated including stage of disease, lymph-node involvement, tumour size, histology and presence of oestrogen and progesterone receptors in the tumour. No correlation was found with serum HA concentration and we conclude that serum HA level is of no prognostic significance in breast cancer. PMID- 1459728 TI - Neutralizing activity of human antibodies against the structural protein of human T-cell lymphotropic virus type I. AB - We have identified and mapped the regions responsible for neutralization in the human T-cell leukemia virus type I (HTLV-I) structural proteins by using region specific human antibodies derived from seropositive blood donors. We have obtained 18 kinds of region-specific antibody (2 in the p19 gag, 10 in the gp46 env and 6 in the gp21 env proteins) from seropositive human plasma by means of an affinity column coupled with the synthetic peptides corresponding to the antigenic regions of the HTLV-I structural proteins. These antibodies were highly specific in ELISA using synthetic peptides as an antigen. Subsequently, we examined the neutralizing activity expressed by the inhibition of virion-induced syncytium formation by region specific antibodies. Twelve of 16 antibodies derived from the env protein were able to inhibit syncytium formation induced by co-cultivation of 8C cells with HTLV-I antigen-positive T cells. The antibodies derived from the p19 gag protein and the seronegative plasma used as the control showed no significant activity. The sequences recognized by the 10 neutralizing antibodies were sites corresponding to amino acids 20 to 49, 89 to 115, 136 to 160, 175 to 199, 213 to 236, 235 to 254, 277 to 292, 332 to 352, 350 to 386, 382 to 403, 426 to 448 and 458 to 488 from the amino terminal of the env protein. These observations suggest that the neutralizing epitopes were widely distributed in the env proteins of HTLV-I. PMID- 1459729 TI - Establishment of a murine model of malignant mesothelioma. AB - Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with previous asbestos exposure and is generally found to be resistant to conventional forms of therapy. Adequate scientific and clinical assessment of this disease has been severely limited by the relatively low incidence of mesothelioma and the lack of representative cell lines and animal models. The purpose of this study was to develop an asbestos-induced murine model of MM both as an in vivo-passaged malignancy and as in vitro-established cell lines. Such a model system would be invaluable for use in the study of various cellular, molecular and genetic aspects of the disease, and for the pre-clinical evaluation of potential therapeutic agents. BALB/c and CBA mice were injected intraperitoneally with crocidolite asbestos. Seven to 25 months after exposure, 35% of the mice developed mesothelioma (5 BALB/c, 9 CBA), as determined by standard cytological and histological parameters. From these primary tumours, 12 continuously growing cell lines (5 BALB/c, 7 CBA) were established in culture. All have been confirmed as mesothelioma by cytological and ultrastructural (electron microscopy) analyses. These lines have been in culture for 7 to 24 months and have achieved passages above 32 (range 32 to 106). As in the human disease, the murine mesothelioma lines vary in their morphology and growth rates (doubling times ranging from 14 to 30 hr). All cell lines produced tumours when injected into syngeneic mice. PMID- 1459730 TI - Growth of Hodgkin cell lines in severely combined immunodeficient mice. AB - No animal model exists for the in vivo growth of Hodgkin's-lymphoma-derived cells. Neither unmanipulated Hodgkin's-disease(HD)-derived cell lines nor primary biopsy tissue could be grown in nude mice. Since the severe combined immunodeficient (SCID) mouse has been reported to be a better recipient for transplanted human lymphatic tissue than the nude mouse, we tested whether SCID mice provide suitable conditions for the in vivo growth of HD cell lines. Tumorigenicity of HD cells was tested in untreated and pre-treated SCID mice and in another combined immunodeficient mouse strain, beige/nude/X-linked immunodeficient (BNX) mouse. SCID mice supported in vivo growth of the 6 HD cell lines tested (L428, L540, L591, DEV, HD-LM2, KM-H2). Only one of the 6 lines (DEV) was tumorigenic in BNX mice. No HD cell line proliferated in T-cell deficient nude mice. Thus, in vivo growth of HD cell lines appeared to be related to the degree of host immunodeficiency. Additional growth supportive treatments such as fibrosarcoma co-transplantation, intraperitoneal mineral oil injection or immunosuppressive pre-treatment (anti-asialo-GMI-antibody injection) permitted growth of 3 additional HD cell lines in BNX mice. The immunophenotype and karyotype of explanted graft cells were identical to the original cell lines. Our experiments describe an effective and reproducible xenograft model for growth of Hodgkin's-disease-derived cell lines. This may be of value for elucidating the growth characteristics of Hodgkin's-lymphoma-derived cells as well as for testing new therapeutic regimens. PMID- 1459731 TI - Antibody against p58 surface antigen of RA-2 rat rhabdomyosarcoma cells inhibits their metastatic activity. AB - Antibodies generated against the whole membrane preparation isolated from rhabdomyosarcoma RA-2 cells were shown by immunoblotting and immunoaffinity chromatography to recognize 58-kDa polypeptide, p58. The latter was confirmed to be a surface molecule in a test of radioiodination of RA-2 membrane by lodogen. The antibodies added to a suspension of RA-2 cells before their inoculation into rats decreased metastatic activity 50-fold without any noticeable influence on RA 2 proliferation level and viability. The data indicate that masking of p58 surface antigen by antibodies could make RA-2 cells unable to form experimental metastases in lung. We suggest that p58 may participate in the specific recognition by RA-2 of lung endothelial cells. PMID- 1459732 TI - DOK, a cell line established from human dysplastic oral mucosa, shows a partially transformed non-malignant phenotype. AB - There are many reports of cell lines being established from human oral squamous cell carcinomas but apparently none of cell lines from dysplastic or "pre malignant" oral mucosa. We describe here the isolation and characterization of a cell line, DOK (dysplastic oral keratinocyte), from a piece of dorsal tongue showing epithelial dysplasia. The tissue was obtained from a 57-year-old man who was a heavy smoker prior to the appearance of a white patch on his tongue. Eleven years later a squamous-cell carcinoma developed at the site and was excised. Subsequently the remaining dysplasia was removed, and it was from a piece of this that the primary cell cultures which eventually gave rise to DOK were initiated. The DOK line has been single-cell cloned and is apparently immortal. It grows in the absence of 3T3 feeder cells, is anchorage-dependent for growth and is non tumorigenic in nude mice. The keratin profile of the cells shows a striking similarity to that of the original tongue dysplasia. The karyotype of DOK is aneuploid and complex. By PCR and oligonucleotide hybridization on dot blots, codons 12, 13 and 61 of Ha-ras, Ki-ras and N-ras in DNA extracted from DOK cells were shown to be normal. Immunohistochemistry showed no abnormal, i.e., elevated expression of the onco-suppressor protein p53. Because of its origin and partially transformed phenotype, DOK presents an opportunity to study whether specific carcinogens associated with tobacco and areca nut can cause malignant transformation of oral keratinocytes in vitro. PMID- 1459733 TI - Protection by muscimol against gastric carcinogenesis induced by N-methyl-N' nitro-N-nitrosoguanidine in spontaneously hypertensive rats. AB - The effects of prolonged administration of the gamma-aminobutyric acid receptor agonist muscimol on enhanced induction of gastric carcinogenesis by N-methyl-N' nitro-N-nitrosoguanidine (MNNG) in spontaneously hypertensive rats (SHR), and on the norepinephrine concentration in the gastric wall and the labeling index of gastric mucosa were investigated. SHR and normotensive Wistar Kyoto (WKY) rats as controls were given a solution of MNNG (25 micrograms/ml) for 25 weeks and then i.p. injections of 0.5 mg/kg body weight of muscimol every other day. In control WKY rats, gastric cancers were found in 1 (7%) of 14 rats examined at week 52. In SHR treated with NaCl solution only, the incidence of gastric cancers was significantly increased to 50% compared with that in control WKY rats. However, treatment of SHR with muscimol significantly increased its incidence to 12% compared with the value in SHR treated with NaCl solution only. The norepinephrine concentration in the gastric wall and the labeling index of the gastric mucosa were significantly greater in SHR than in WKY rats. Prolonged administration of muscimol to SHR significantly reduced the norepinephrine concentration in the antral portion of the gastric wall or the labeling index of the antral epithelial cells. These findings indicate that long-term treatment of SHR with muscimol attenuated the enhancement of gastric carcinogenesis in SHR. PMID- 1459734 TI - Analysis of factors associated with the tumorigenic potential of 12 tumor clones derived from a single rat colon adenocarcinoma. AB - We analyzed several factors which could influence the immunogenicity of colon tumor cells, using a series of clones derived from a single chemically induced rat adenocarcinoma cell line. These clones display variable tumorigenic potential in syngeneic immunocompetent animals, and it has been established that in this model the tumorigenicity of the cells depends on their ability to escape immune surveillance. The results show an absence of relationship between tumorigenicity and expression of MHC-class-I antigens, cell adhesion to rat fibroblasts or fibroblast extracellular matrix. The secretion of latent and active TGF beta I appeared to be quite variable from one clone to the other, but was unrelated to tumorigenicity. Unexpectedly, some regressive clones produced elevated levels of this cytokine, suggesting that in this model, spontaneous secretion of TGF beta I is not sufficient to impair the immune system of the host. In contrast, the more tumorigenic clones were more resistant than less tumorigenic ones to cytotoxicity mediated by NK or LAK cells. They also showed arrest of cell proliferation after reaching confluence, something not observed in the less tumorigenic clones. Finally, the strongest relationship with tumorigenicity was found for expression of blood-group carbohydrate antigens. Increased expression of blood-group-H antigen and, conversely, decreased expression of beta-galactoside precursors of this antigen correlated with increased tumorigenicity. PMID- 1459735 TI - Functions of estrogens and anti-estrogens in the rat endometrial adenocarcinoma cell lines RUCA-I and RUCA-II. AB - Inbred rats of the DA/Han and BDII/Han strains have been proposed as suitable model systems for studying hormonal carcinogenesis, because they die mainly from hormone-dependent endometrial adenocarcinoma. Here we characterize the RUCA-I cell line derived from an endometrial adenocarcinoma of an inbred DA/Han rat and the RUCA-II cell line derived from an endometrial adenocarcinoma of an inbred BDII/Han rat. The RUCA-I cell line, if transplanted to the neck of female DA/Han rats, gives rise to endometrial adenocarcinomas at the ectopic site. The morphology of these ectopically grown tumors is predominantly of the moderately differentiated sub-class. In contrast, ectopic tumor growth of the RUCA-II cell line can be observed only if cells are transplanted to athymic nude mice. Biochemically, both cell lines are characterized by the stable expression of estrogen receptors. However, no statistically significant mitotic response of RUCA-I and RUCA-II cells to estradiol was measurable, and no induction of expression of the progesterone receptor by estradiol was detectable, although estradiol transformed the estrogen receptor into its stable DNA-binding state. In contrast, the rate of proliferation of RUCA-I but not of RUCA-II cells was reduced in the presence of 10(-6) M tamoxifen. From these results we conclude that (i) both cell lines, RUCA-I and RUCA-II, represent a new and promising endometrial tumor model; (ii) the mechanism of the hormone-dependent growth regulation of RUCA-I and RUCA-II cells is obviously impaired; (iii) the RUCA-I cell line appears to be a suitable model system for the study of molecular aspects of estrogen- and tamoxifen-dependent gene expression. PMID- 1459736 TI - The development of human tumor-cell resistance to TNF-alpha does not confer resistance to cytokine-induced cellular cytotoxic mechanisms. AB - We have derived a TNF-alpha-resistant clone (RA-I) from the parental TNF sensitive human breast-adenocarcinoma cell line (MCF-7). The acquisition of TNF resistance was not associated with endogenous TNF production or with differential levels of TNF receptors since both MCF-7 and RA-I display comparable TNF-receptor expression. We have investigated the relationship between acquisition of resistance to TNF and susceptibility to lysis by cytokine-activated effectors. Experiments were performed using human peripheral-blood monocytes stimulated with IL-2, IFN or GM-CSF, and lymphokine-activated killer cells as effector cytotoxic cells. Our data indicate that both TNF-resistant (RA-I) and TNF-sensitive (MCF-7) cells were killed by IL-2-activated monocytes. Incubation of monocytes with IFN also resulted in the activation of their tumoricidal activity against MCF-7 and RA-I. When stimulated monocytes were pre-incubated in the presence of a TNF specific neutralizing monoclonal antibody, prior to co-culture with target cells, no effect on their lytic capacity was observed. Thus, the monocyte killing does not appear to involve the membrane form of TNF. These observations suggest that, in our experimental system, IL-2 and IFN are able to induce non-TNF-mediated mechanisms of cytotoxicity by monocytes. Experiments performed using GM-CSF and LPS for monocyte stimulation indicate that, although both reagents were efficient in inducing the membrane form of TNF on monocytes, they did not enhance the cell killing capacity towards MCF-7 and RA-I targets. Furthermore, using IL-2 stimulated LGL as effector cells, we show in this study that the TNF-resistant clone RA-I was as sensitive as MCF-7 to human LAK cells. PMID- 1459737 TI - Second-messenger pathways involved in the regulation of survival in germinal centre B cells and in Burkitt lymphoma lines. AB - Spontaneous apoptosis in germinal-centre (GC) B cells can be prevented by treatment with anti-immunoglobulin (Ig). By contrast, susceptible group-I Burkitt lymphoma (BL) cells can be driven to apoptosis by anti-Ig. The second-messenger pathways involved in the regulation of apoptosis in GC B lymphocytes and in BL cell lines were studied using pharmacological agonists or inhibitors of intracellular calcium ([Ca2+]i) and protein kinase C (PKC). Anti-Ig was found to mobilize Ca2+ in group-I cells. Pre-incubation with the Ca2+ chelator EGTA partially reduced apoptosis induced by anti-Ig or by Ca2+ ionophore in group-I BL cells. Activation of PKC with phorbol ester reduced such Ca(2+)-driven programmed cell death (PCD) to control levels of apoptosis. Apoptosis in group-I BL cell lines could also be triggered by the kinase inhibitors staurosporine and Ro-31 8220 at concentrations selective for PKC activity. Expression of the bcl-2 protein in BL group-I cells following gene transfer affords protection from apoptosis induced by ionomycin or anti-Ig. In the present study, bcl-2 was additionally found to protect from apoptosis driven by staurosporine. The high levels of spontaneous apoptosis exhibited by normal GC B cells were reduced, but not abrogated, by co-culture with phorbol ester. These results indicate that, in group-I BL cells, imbalance in the phosphoinositide pathway of signalling, in favour of [Ca2+]i and away from PKC, results in apoptosis: constitutive phosphorylation of key proteins by PKC may therefore suppress apoptosis in BL as well as in GC B cells. PMID- 1459738 TI - Analysis of two human monoclonal antibodies against melanoma. AB - B cells derived from peripheral-blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) from a patient with a high serum antibody titer to autologous melanoma were transformed with Epstein-Barr virus (EBV) and evaluated for reactivity against autologous tumor. B cells producing antibody reactive with autologous tumor and unreactive with normal fibroblasts were detected both in TIL and in PBL. One cell line derived from PBL and another derived from TIL sustained production of tumor-reactive antibody for 10 weeks and over 15 months respectively. The cell line derived from PBL, 2D11, produced an antibody reactive with a trypsin-resistant antigen expressed on the cell membrane of autologous and allogeneic melanoma cell lines. The cell line derived from TIL, 1F6, produced an antibody reactive with a cell-surface glycoprotein expressed by 5 autologous melanoma cell lines derived from 5 different metastases and 16/19 allogeneic melanoma cell lines. 1F6 also showed reactivity with cell lines derived from a blue nevus, a congenital nevus, an astrocytoma, and 1/4 renal-cell carcinomas; but it was not reactive with 5 foreskin melanocyte cell lines, 2 normal fibroblast lines, 5 leukemia/lymphoma lines, 8 lung-cancer lines, 8 glioblastoma lines, or lines derived from 1 ovarian carcinoma, 1 colon carcinoma, 1 vulvar carcinoma, 1 fibrosarcoma, 1 murine melanoma, or 4 murine leukemia/lymphomas. We describe here an antibody that detects a new melanoma specificity obtained by EBV transformation of tumor-infiltrating B cells. PMID- 1459739 TI - Cancer-cell traffic in the liver. I. Growth kinetics of cancer cells after portal vein delivery. AB - Following the intrasplenic injection of B16F10 melanoma cells into mice, at first single cells, and later multicellular tumor foci were observed at different times in the liver. Cell numbers and tumor volumes were determined over the next 12 days, by confocal microscopy of thick liver sections. Fifteen minutes after injection, approximately 20% of the melanoma cells were identified in the liver microvasculature; after 48 hr, only 0.68% of these retained morphologic integrity; by 5 days only 0.13% of the originally detected cells incorporated BUdR; and, by 12 days, these subsequently grew into tumor nodules. Tumor volume changes with time were not exponential and, following a non-replicative period during the first 2 1/2 days, the volume doubling times increased from approximately 8 to 39 hr at 12 days. BUdR incorporation indicated that this was probably due to a diminishing proliferative fraction in the cancer-cell population. When animals were killed at 12 days, tumor foci were centered on the liver sinusoids and appeared to represent expansive growth of arrested cells, with no evidence of parenchymal invasion by migrating cancer cells, in spite of the absence of a subendothelial basement membrane. Our direct observations indicate that, in this model system, the post-delivery phase of hepatic colonization is characterized by high levels of inefficiency with respect to cancer-cell survival, growth and extravasation. PMID- 1459740 TI - Proliferation of human colon cancer cells: role of epidermal growth factor and transforming growth factor alpha. AB - Human colon cancer cells produce and secrete a variety of polypeptide growth factors. The functional role of these growth factors, however, is poorly understood. Though the secretion of epidermal growth factor (EGF)-like activity and EGF-related molecules by human colon cancer cells in culture has been reported, it is not known whether colon cancer cells produce and secrete EGF, and the functional role of EGF in the growth control of these cells is also unknown. We have shown that EGF acts as a potent growth stimulator on the moderately differentiated Moser colon cancer cell line and as an inhibitor on the highly metastatic KM12SM cell line. In the present study, we show that EGF is produced by human colon cancer cells and characterize the levels of EGF mRNA expression and EGF protein secretion from 8 human colon cancer cell lines. The cell-surface EGF receptors on these cell lines were also characterized by radiolabeled ligand binding and Scatchard analyses. All the cell lines expressed EGF mRNA and secreted EGF. Both high- and low-affinity subtypes of EGF receptor were detected on 7 of the cell lines. These lines also secreted transforming growth factor (TGF)alpha. Some cell lines exhibited a proliferative response to treatment with either exogenous EGF or TGF alpha, while others did not respond to treatment with these growth factors. Antibody-blocking experiments, using anti-EGF or anti-EGF receptor antibody, suggested that these cell lines could be broadly classified into 2 groups in terms of their autocrine or paracrine growth regulation via the cell-surface EGF receptor: (1) cells that utilized EGF and/or TGF alpha; and (2) cells that did not utilize EGF or TGF alpha (via the cell-surface receptor), even though they secreted abundant amounts of these growth factors. PMID- 1459741 TI - Orthotopic growth and metastasis of human prostate carcinoma in nude mice after transplantation of histologically intact tissue. PMID- 1459742 TI - Cholesterol consensus: a trans-Atlantic perspective. Amsterdam, The Netherlands, 31-October-1 November 1991. AB - This consensus document has been drawn up following the round-table conference 'Cholesterol Consensus: a Trans-Atlantic Perspective', Amsterdam, 31 October and 1 November 1991. Its recommendations are as follows. Elevated plasma cholesterol level should be viewed as one of a number of important risk factors that contribute to the high incidence of coronary heart disease in industrialized societies. Control of lipid abnormalities forms an essential part of an overall preventive strategy of risk factor reduction. Both population and individual strategies are required. To reduce the mean plasma cholesterol levels of populations, a multidisciplinary approach is needed, involving the health-care professions, government, food manufacturers and distributors, community and consumer organizations, and the media. While it is desirable for all individuals to know their plasma cholesterol level, universal screening is recommended only where resources for treatment and follow-up are sufficient to cope with the case load detected. As an interim measure, screening should be focused on individuals at special risk. The recommendations of the European Atherosclerosis Society and the U.S. National Cholesterol Education Program should be followed with regard to thresholds for treatment by dietary counselling and pharmacological methods, and targets for cholesterol reduction. These recommendations should be periodically reviewed as new research data becomes available. A number of key areas for research are listed. PMID- 1459743 TI - Catecholamine excretion and heart rate as factors of psychophysical stress in table tennis. AB - Table tennis, like tennis, squash and badminton, is a racket sport. All these sports have in common a rapid succession of mostly short-term maximal or submaximal efforts and short recovery phases. The goal of this paper is to investigate the psychophysical stress in table tennis by means of the stress hormones epinephrine and norepinephrine. The catecholamines were determined from urine samples. 16 Austrian top-level table tennis players were examined. There were 8 female and 8 male players in this group. The catecholamine excretion at rest (R), training (TR), practice competition (PC), competition (C) and treadmill ergometry (TE) are indicated in ng/min of collecting time. When the group is divided according to sex, we find marked differences in the catecholamine release. While the epinephrine excretion during and after training and practice competition is basically the same, it is lower during and after treadmill ergometry and higher after competition. The same result was found with respect to norepinephrine excretion. The ratio between norepinephrine and epinephrine was 4:1 at rest and during and after treadmill ergometry, 6:1 during and after training, 5:1 during and after the practice competition and 2:1 during and after the competition. The investigation showed that a table tennis competition puts high stress on the player. The mental component should therefore receive much more importance in order to keep the stress low. PMID- 1459744 TI - Haemorheology and exercise: intrinsic flow properties of blood in marathon running. AB - Haemorheological and haematological parameters were studied in venous blood samples taken from 8 endurance-trained athletes before and after a marathon run. Viscometry was performed in a 20 microns glass capillary and in a Couette viscometer. Apparent blood viscosity was lower in the capillary than in the rotational viscometer, but significant differences between pre- and post-run samples were not observed in either system. This is presumably due to the absence of changes of haematocrit (pre-run [mean +/- SD]: 0.453 +/- 0.016, post-run: 0.456 +/- 0.018). Although protein concentration increased significantly from 70.8 +/- 2.1 g/l (pre-run) to 76.0 +/- 3.9 g/l (post-run), the difference of plasma viscosity was not statistically significant (pre-run: 1.26 +/- 0.03 cP, post-run: 1.30 +/- 0.07 cP). In all samples, plasma viscosity showed a significant positive correlation with total protein, globulin, albumin, but not with fibrinogen concentration. Cone-plate aggregometry and a filtration technique were used to evaluate red cell aggregation and deformability, two determinants of blood rheology which also were not different between pre- and post-run samples. The absence of viscosity changes in relation to the marathon run may be due to the relative stability of blood and plasma volume, which can be deduced from haematological parameters. Alterations of plasma composition (e.g. acidosis or hyperosmolality) seem to cause only minor, if any, changes of microrheological cell properties. PMID- 1459745 TI - Determining the variability of performance on Wingate anaerobic tests in children aged 6-12 years. AB - In two parts, this study investigated variability of performance in Wingate anaerobic tests (WAnTs) of normal, healthy, male children aged six, eight, ten and twelve years. The purpose of the first part of the study was to investigate the mean coefficient of variation (C.V. = [S.D./X].100) of children who performed four WAnTs over a period of four weeks. The results revealed age-related differences in the performance data of peak power (PP) and mean power (MP) but no differences between age groups in fatigue index (FI%) = [PP-Pend)/PP.100]. C.V. data from this group of children did not differ significantly between ages in any of the dependent variables. Coggan and Costill (5) measured the variability of male adults during 30 seconds of highly intense cycling and reported C.V.s in PP and MP performances of 6.7 and 6.5%, respectively. C.V.s of children in the first part of the present study were 7.3 and 6.8% for PP and MP, respectively. The C.V. in the FI% of the children (26.7%) however differed substantially from the previously studied adults (10.3%). The second part of the study was conducted to examine the C.V. in FI% performances of children in the WAnT. The purpose of this part of the study was to examine the extent to which a computerized onscreen game, which was linked to pedal cadence affected the variability of children performing WAnTs. A significant decrease was obtained in the C.V. of the FI% in the presence of the computerized feedback game (16.3 and 23.6, with and without the game, respectively). It is suggested that game-based testing procedures may ensure more consistent result in the assessment of pediatric populations. PMID- 1459746 TI - A new approach for the determination of ventilatory and lactate thresholds. AB - In order to determine the ventilatory threshold (VT) and the lactate threshold (LT) in a reliable way, a new method is proposed and compared with conventional methods. The new method consists of calculating the point that yields the maximal distance from a curve representing ventilatory and metabolic variables as a function of oxygen uptake (VO2) to the line formed by the two end points of the curve (Dmax method). Male cyclists (n = 8) performed two incremental exercise tests a week apart. Ventilatory/metabolic variables were measured and blood was sampled for later lactate measurement during each workload and immediately after exercise. No statistical differences were observed in the threshold values (expressed as absolute oxygen uptake; VO2) determined by the Dmax method and the conventional linear regression method (according to O2 equivalent; EqO2) and venous blood at the onset of blood lactate (OBLA), while VT assessed with the conventional linear method (according to the slope of CO2 output; Vslope) yielded significantly lower threshold values. Similar results were obtained from the reproducibility test. Thus, the Dmax method appears to be an objective and reliable method for threshold determination, which can be applied to various ventilatory or metabolic variables yet yield similar results. The results also showed that breathing frequency can be used to determine VT. PMID- 1459747 TI - Accuracy of pulse oximetry during exercise stress testing. AB - Pulse oximetry is used extensively during exercise stress-testing in the clinical and sports medicine settings. There are few validation studies to assess the appropriateness of using pulse oximetry under conditions of potentially compromised peripheral blood flow. To study the accuracy of pulse oximetry during severe exercise stress, 10 athletes undertook 3 bouts of exhaustive exercise; once at an intensity requiring VO2max (max), once at 115% of VO2max (Smax), and once at Smax while FIO2 was increased to 0.30. The results indicate relatively large underestimations occur when pulse oximetry is used to estimate %SaO2 during exercise, when compared to the criterion samples of gas analysis in arterial blood. These differences were exacerbated as the exercise intensity increased from a mean(+/- SE) difference of 2.9 +/- 0.7 %SaO2 at max to 4.6 +/- 0.7 %SaO2 at Smax. Breathing a higher FIO2 reversed the hypoxemia that occurred during the normoxic exercise, however, pulse oximetry measurements failed to detect this alteration in %SaO2. Estimates of oxygen saturation during severe exercise using pulse oximetry should be viewed with caution, as potentially large errors may occur. PMID- 1459748 TI - Maximal-intensity intermittent exercise: effect of recovery duration. AB - Seven male subjects performed 15 x 40m sprints, on three occasions, with rest periods of either 120 s (R120), 60 s (R60) or 30 s (R30) between each sprint. Sprint times were recorded with four photo cells placed at 0, 15, 30 and 40 m. The performance data indicated that whereas running speed over the last 10 m of each sprint decreased in all three protocols (after 11 sprints in R120, 7 sprints in R60 and 3 sprints in R30), performance during the initial acceleration period from 0-15 m was only affected with the shortest rest periods increasing from (mean +/- SEM) 2.58 +/- .03 (sprint 1) to 2.78 +/- .04 s (spring 15) (p < .05). Post-exercise blood lactate concentration was not significantly different in R120 (12.1 +/- 1.3 mmol.l-1) and R60 (13.9 +/- 1.2 mmol.l-1), but a higher concentration was found in R30 (17.2 +/- .7 mmol.l-1) (p < .05). After 6 sprints there was no significant difference in blood lactate concentration with the different recovery durations, however, there were significant differences in sprint times at this point, suggesting that blood lactate is a poor predictor of performance during this type of exercise. Although the work bouts could be classified primarily as anaerobic exercise, oxygen uptake measured during rest periods increased to 52, 57 and 66% of maximum oxygen uptake in R120, R60 and R30, respectively. Evidence of adenine nucleotide degradation was provided by plasma hypoxanthine and uric acid concentrations elevated post-exercise in all three protocols. Post-exercise uric acid concentration was not significantly affected by recovery duration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459749 TI - Physiological changes in male competitive cyclists after two weeks of intensified training. AB - To study the physiological response to heavy training, seven male competitive cyclists intensified their normal training program for two weeks (IIT) in order to achieve a state of short-term overtraining. The subjects underwent a graded cycle ergometer test to exhaustion, an outdoor 8.5 km time trial and a computerized test to study reaction time and visual perception, before, during and after the two weeks of intensified training and after two weeks of recovery. Furthermore subjects kept a daily log in the form of a questionnaire. After two weeks of IIT all subjects showed symptoms of overtraining: the general state of well being declined as indicated by the questionnaire while performances on time trial (mean +/- SEM: 830 +/- 14 sec-871 +/- 19 sec), contests and maximal power output (mean +/- SEM: 336 7 watt-310 +/- 5 watt) declined significantly. Maximal (mean +/- SEM 11.8 +/- 1.1 mmol.l-1-5.9 +/- 0.5 mmol.l-1) and submaximal lactate values were significantly lowered during ergometer test after the IIT, while the workload at the 4 mmol point increased significantly (mean +/- SEM 234 +/- 10 watt-267 +/- 13 watt). Sleeping heart rate increased significantly (mean +/- SEM 49.5 +/- 9.3 BPM-54.3 +/- 8.8 BPM). Maximal heart rate (mean +/- SEM 185 +/- 3 BPM-178 +/- 2 BPM, mean heart rate during the time trial (mean +/- SEM 178 +/- 2 BPM-169 +/- 2 BPM) and VO2max (mean +/- SEM 4801 +/- 121 ml.min-1-4409 +/- 101 ml.min-1) were all significantly lowered by the IIT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459750 TI - Response of beta-endorphin and estradiol to resistance exercise in females during energy balance and energy restriction. AB - The acute effect of weightlifting on beta-endorphin and estradiol was studied in experienced female recreational weightlifters. Five eumenorrheic females completed two months of testing, each with a different sequence of testing conditions (SEQ1 and SEQ2). In SEQ1, a week of weight maintenance diet and prescribed exercise (3 d.wk-1, 3 sets, approximately 85% 1 RM, 10-12 reps, eight lifts) beginning on d 11 of their menstrual cycle was followed by measurement of hormone response to a weightlifting bout during energy balance (EBAL) on d 18. This included blood sampling via a catheter before, just after, and at 15 and 30 min of recovery. The women consumed 500 kcal per day for the next 48 hrs and then repeated the weightlifting test during negative energy balance (NEBAL). SEQ2 was similar except that the 48 hrs of NEBAL preceded the EBAL test condition. Estradiol and beta-endorphin increased from baseline to immediately post exercise under both dietary conditions but was significant only during NEBAL. Estradiol increased 1.6 fold and beta-endorphin 3.7 fold by the end of the resistance exercise bout during NEBAL. Both hormones were also elevated for a longer time during recovery in the NEBAL condition. Since estradiol and beta-endorphin can suppress gonadotropin release, it is possible that repeated elevations in these hormones during weightlifting, especially concurrent with energy restriction, could contribute to disruption of the menstrual cycle. PMID- 1459751 TI - Seasonal deterioration of selected physiological variables in elite male skiers. AB - The purpose of this study was to determine whether seasonal deterioration in physiological variables could be observed in skiers. Eighteen international male British downhill, free-style, and speed skiers were subjected to a maximal treadmill running test, a 30-s Wingate test, and isokinetic dynamometry at the beginning, middle, and end of the 1989-90 competition season. Maximal oxygen intake (VO2max) and respiratory anaerobic threshold (T vent) were among the parameters measured on the treadmill test, while peak and mean power outputs were measured during the Wingate test. During dynamometry, knee flexors and extensors were bilaterally assessed at 1.04 and 3.14 rad.s-1. Mean VO2max (p < 0.01) and mean T vent (p < 0.05) were lower at the end compared to the beginning, but not compared to the middle of the competition season. The isokinetic test demonstrated lower mean peak torques at 1.04 rad.s-1, for the knee extensors measured at the end of the season, compared with both the start (p < 0.01) and the middle (p < 0.05). Also at 1.04 rad.s-1, knee flexors produced lower torques at the end than the start of the season (p < 0.05). No further statistical differences were found. It was concluded that seasonal deterioration in key physiological variables such as aerobic endurance and muscle strength, can be observed in elite alpine skiers, and that in-season fitness training programmes should take account of this. PMID- 1459752 TI - The effect of exercise on anterior knee laxity in female basketball players. AB - To study the effect of physical activities on the anterior laxity of the knee joint, the anterior knee laxity of female semi-professional basketball players was measured during a typical day. The participants worked in the office in the morning, and practiced in the afternoon, which included a 60 minute warm-up, followed by a 150 minute game style practice. The laxity was measured six times in one day at different activity levels. The anterior knee laxity did not change during sedentary work in the morning, but increased significantly with game style practice. After 1 1/2 hours the increased anterior knee laxity had not recovered completely. However, after five hours it had recovered completely. PMID- 1459753 TI - Dermatologic lasers: three decades of progress. PMID- 1459754 TI - Role of food allergy in atopic dermatitis. PMID- 1459755 TI - The causative agent of bacillary angiomatosis. PMID- 1459756 TI - Incident light microscopy: reflections on microscopy of the living skin. PMID- 1459757 TI - Vitiligo in children. AB - In our study the relative incidence of vitiligo among new patients was 2.6%. Twenty percent were children and 74% were adults. Of the 90 children, 38.9% were boys, and 61.1% were girls. This sex difference was statistically highly significant. The adult sex-ratio was not statistically significant. The relative incidence of the clinical subtypes in children and adults was compared, and the difference was found to be statistically highly significant only in the case of vitiligo vulgaris and segmental vitiligo. On the basis of the difference in the sex-ratio and in the relative incidence of the subtypes of vitiligo vulgaris and segmental vitiligo, we feel that childhood vitiligo is a distinct subtype of vitiligo. PMID- 1459758 TI - Specific cutaneous lesions in a CD8+ peripheral T-cell lymphoma. AB - Histopathologic, immunohistochemical, and ultrastructural studies were carried out on cutaneous lesions of a 43-year-old man with an aggressive peripheral T cell lymphoma involving the lung, central nervous system, bone marrow, and skin. Some results are distinctive and not previously reported, such as extremely strong epidermotropism, aberrant CD8+ immunophenotype with lack of one pan T antigen (CD5), and giant cytoplasmic granules. We discuss these features comparing them with other hematologic malignancies usually involving the skin, such as cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, angiocentric lymphomas, and malignant histiocytosis. PMID- 1459759 TI - Lack of predictive factors in late recurrence of stage I melanoma. AB - Through the UCLA tumor registry, patients treated for late-relapse malignant melanoma (after a 10-year disease-free interval) were identified and studied retrospectively. The patients were studied in regards to age, sex, primary site of the lesion, the disease-free interval, elective lymph node dissection, mode of recurrence and survival time following relapse. The histologic characteristics studied included the maximal tumor thickness, Clark's levels, rate of mitoses, and presence of ulceration. Based on the 0.84% incidence of late-relapse, the recommendation for annual life-time follow-up examinations for all patients with malignant melanoma is supported. PMID- 1459760 TI - Reaction in leprosy: acute phase reactant response during and after remission. AB - Sera from 25 patients with type 1 (Lepra), upgrading and downgrading, and type 2 (erythema nodosum leprosum [ENL]) reactions were assayed, during the reaction and after its clinical remission, for changes in levels of alpha-1-antitrypsin (A1A) and C-reactive protein (CRP). The results were compared with those from normal healthy adults and patients of leprosy without history and/or clinical evidence of reaction. The A1A levels correlated better with changes in status of type 1 reaction; whereas CRP levels correlated well with alterations in type 2 reactions and were definitely superior to A1A in this situation for monitoring the course of these episodes. PMID- 1459761 TI - Multiple basal cell carcinoma in tropical Australia. AB - No association between HLA DR1 and the development of multiple basal cell carcinomas (BCC) was found among patients who had lived at least two-thirds of their lives in the tropics. The percentage of patients with multiple BCCs increased with age; this was different from what has been found in people living in the temperate zone of Australia. PMID- 1459762 TI - Multiple bone metastases from basal cell carcinoma. PMID- 1459763 TI - Malignant spitz nevus. PMID- 1459764 TI - Acute febrile neutrophilic dermatosis (Sweet's syndrome) associated with Behcet's disease. PMID- 1459765 TI - Acute febrile neutrophilic dermatosis (Sweet's syndrome) associated with prostate adenocarcinoma and a myelodysplastic syndrome. PMID- 1459766 TI - Papulonodular cutaneous mucinosis associated with systemic lupus erythematosus. PMID- 1459767 TI - Systemic lupus erythematosus with hereditary deficiency of the fourth component of complement. PMID- 1459768 TI - Cutaneous myiasis: a simple and effective technique for extraction of Dermatobia hominis larvae. AB - We describe two patients with cutaneous myiasis caused by Dermatobia hominis. Three larvae were removed successfully by a simple technique that involved the injection of each larva with 2 mL of lidocaine, making surgical extraction by incision and exploration unnecessary. PMID- 1459769 TI - Lymphedema treated by microwave and elastic dressing. AB - For lymphedema, surgical treatment is contraindicated and other conservative treatments including oral medicine are not sufficient. Treatment with microwave and elastic dressing has been evaluated in 30 cases of lymphedema with 11 control patients who received only one of the two treatments. Twenty-four patients were effectively treated. In six, edema was not decreased as compared with reduction due to daily physical activity. It was observed that the earlier the patient was treated after onset of edema, the better the results. Six of 10 control patients who received only elastic dressing showed slight decrease in edema. A patient who received only microwave did not show any improvement. There was no recurrence in half of the treated patients. Treatment of lymphedema by microwave and elastic dressing appears satisfactory, particularly when given at an early stage of the disease. PMID- 1459770 TI - Tinea versicolor treated with fluconazole shampoo. PMID- 1459771 TI - Neutrophils in cerebrospinal fluid of a patient with acute febrile neutrophilic dermatosis (Sweet's syndrome) PMID- 1459772 TI - Alopecia and cutis verticis gyrata due to traction presenting as headache. PMID- 1459773 TI - Granuloma annulare following herpes zoster. PMID- 1459774 TI - Iritis and Wells' syndrome. PMID- 1459775 TI - Porokeratosis and cardiac transplantation. PMID- 1459776 TI - The survival of Ostertagia circumcincta and Trichostrongylus colubriformis in faecal culture as a source of bias in apportioning egg counts to worm species. AB - When cultured alone or concurrently with Trichostrongylus colubriformis in sheep faeces, Ostertagia circumcincta produced fewer infective larvae per 100 eggs than did T. colubriformis. Averaged over five trials 60% of T. colubriformis eggs were recovered as infective larvae while for O. circumcincta the figure was only 39%. This result was observed for two strains of O. circumcincta and was independent of when larvae were harvested from culture (days 6-10 at 25 degrees C). The mortalities of both species occurred at the first and second larval stages. These observations are of concern when using larval differentiation from faecal culture to make quantitative estimates of worm egg numbers for each species present. Species such as T. colubriformis which have a low mortality during culture are likely to have their egg numbers overestimated when cultured with a species, like O. circumcincta, that suffers high mortality in culture. PMID- 1459777 TI - Metabolism of lipid peroxidation products by the gastro-intestinal nematodes Necator americanus, Ancylostoma ceylanicum and Heligmosomoides polygyrus. AB - Somatic extracts of the three parasitic nematodes Necator americanus, Ancylostoma ceylanicum and Heligmosomoides polygyrus were able to detoxify a model hydroperoxide and a putative natural peroxide by glutathione-dependent peroxidase activity while cytotoxic carbonyls could be metabolized by NADPH-linked reduction activities. Unlike cestodes and digeneans, the nematodes in this study could not enzymatically conjugate carbonyls with glutathione. The results indicate that the three nematodes can protect themselves against possible host-immune initiated lipid peroxidation of their membranes at the level of the hydroperoxide and at the level of cytotoxic carbonyl, although other protective enzymatic mechanisms are also likely to exist (superoxide dismutase and catalase). PMID- 1459778 TI - A strategy for production of monoclonal antibodies to Echinococcus granulosus antigen 5 and antigen B. AB - Serum antibody responses to sheep hydatid cyst fluid (SHCF) and a purified Antigen 5 (Ag5) were examined in ELISA, immunoelectrophoresis (IEP) and immunoprecipitation (IP) to facilitate production of monoclonal antibodies (MAb) to E. granulosus Ag5 and Antigen B (AgB). Although sera from mice immunized with SHCF contained antibodies of various classes, the fusions using these donor mice resulted in mainly anti-AgB MAb, possibly due to the preferential selection of MAb to AgB by the SHCF-based ELISA screening system. Donor mice immunized with Ag5 also produced several classes of antibodies, and the resultant fusions enabled selection of IgG MAb to Ag5. PMID- 1459779 TI - Echinococcus granulosus in sheep: transfer from ewe to lamb of 'Arc 5' antibodies and oncosphere-killing activity, but not protection. AB - Fourteen ewes were orally dosed with 2000 E. granulosus eggs at 2 weeks of age, were mated at 19 months, and produced lambs when the cysts were 2 years old. One week after parturition, all 14 ewes had 'Arc 5' antibodies in their serum, as did 11/14 of their lambs. Fourteen uninfected ewes were immunized three times before parturition with E. granulosus eggs injected intramuscularly. Cysts grew at the first, or first and second site, but not the third, indicating that the ewes were immune prior to parturition. Most sera from these ewes and their lambs, and from 14 control ewes and their lambs, produced precipitin arcs with hydatid cyst fluid, but no 'Arc 5'. All lambs were challenged with 500 eggs 2 weeks after birth. At necropsy, cyst numbers within groups ranged from 3 to > 200, but there was no significant difference between the three groups of lambs. The immunized ewes did not pass a protection to their lambs that was effective when the lambs were challenged. 'Arc 5' antibodies were induced by prolonged infection with cysts, and were not seen in the sera of ewes immunized with eggs, although the eggs developed into cysts at the injection sites. 'Arc 5' antibodies did not protect lambs against infection, and were not correlated with protection in ewes. Subcutaneous injection of oncospheres into four ewes from each group at the time of lamb challenge showed that the immunized ewes were immune to this method of challenge, but the infected and control ewes were not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459780 TI - Apparent lack of genetic variation within Pelecitus roemeri (Nematoda: Filarioidea) from three Australian species of macropodid marsupial. AB - An electrophoretic study of Pelecitus roemeri from Macropus robustus, M. giganteus and Wallabia bicolor revealed no genetic differences at 23 enzyme loci. The genetic data support the existing morphological evidence that P. roemeri from these three hosts represents a single species. The data show no genetic variation between nematodes from the same or different host species collected in northern and southern Australia. This result is discussed briefly in relation to Price's model of parasite speciation. PMID- 1459781 TI - Mucosal mast cell response to Hymenolepis diminuta infection in different rat strains. AB - Five-week-old DA male rats infected with 10 Hymenolepis diminuta cysticercoids showed significant mastocytosis 6 weeks post-infection and low persistence of worms. In F344/N rats, however, no mastocytosis and no worm loss occurred during a 6 week infection. Mucosal mast cells appear to be associated with the expulsion of H. diminuta from DA rats. PMID- 1459782 TI - Persistence of immune response in human toxocariasis as measured by ELISA. AB - The antibody titer was followed in a group of patients, clinically diagnosed with toxocariasis, during a 5 year period. We observed that larvae can survive for at least 5 years in humans. Antigenic stimulation was enough to keep high levels of immunoglobulins over this period. Antibody levels decreased slowly and this pattern is similar to that shown by animal models. PMID- 1459783 TI - Understanding chronic nematode infections: evolutionary considerations, current hypotheses and the way forward. PMID- 1459784 TI - Sensitive detection of trypanosomes in tsetse flies by DNA amplification. AB - African trypanosome species were identified using the Polymerase Chain Reaction (PCR) by targeting repetitive DNA for amplification. Using oligonucleotide primers designed to anneal specifically to the satellite DNA monomer of each species/subgroup, we were able to accurately identify Trypanosoma simiae, three subgroups of T. congolense, T. brucei and T. vivax. The assay was sensitive and specific, detecting one trypanosome unequivocally and showing no reaction with non-target trypanosome DNA or a huge excess of host DNA. The assay was used to identify developmental stage trypanosomes in the tsetse fly. The use of radioisotopes was not necessary and mixed infections could be detected easily by incorporating more than one set of primers in a single reaction. The use of crude preparations of template made the process very rapid. The methodology should be suitable for large-scale epidemiological studies. PMID- 1459785 TI - Effect of genetic type, lactation and management on helminth infection of ewes in an intensive grazing system on irrigated pasture. AB - A survey of helminth infection was conducted in a flock of 290 ewes distributed into Romanov (R), Merinos d'Arles (M) and Romanov x Merinos (R x M) genetic types, grazing irrigated pasture in the south of France. Faecal egg and larval counts were done seven times per year from 1981 to 1984 on homogeneous groups of ewes and then individually once to four times every autumn from 1985 to 1988. Helminth fauna was diverse and more abundant during autumn. High levels of strongyle infection occurred in the ewes that remained on the same irrigated pastures during summer. Moving to Alpian pastures during the summer lowered autumnal infection. Significant differences between genotypes in intensity of infection were observed in the order R > R x M > M for strongyles (Teladorsagia circumcincta and/or Trichostrongylus vitrinus, Chabertia ovina and/or Oesophagostomum venulosum, Nematodirus spp.), Moniezia spp. and Dictyocaulus filaria. The hierarchy was reversed for Fasciola hepatica infection and not consistent from one year to another for protostrongylid infections. The effect of lactation intensity on the postparturient rise was studied by equilibrating number of ewes according to reproductive status (zero, one or two lambs in lactation). Merino ewes with two lambs in lactation, as well as primiparous Romanov ewes, had significantly higher strongyle infections than the others. The repeatabilities of the larval and egg counts between the four trial years were 0.24, 0.23 and 0.16, respectively, for protostrongyles, Nematodirus and strongyles, with higher intra-annual values for protostrongyles and inconsistently significant results for strongyles due to the presence of several species. PMID- 1459786 TI - Synergistic growth studies of Entamoeba gingivalis using an Ecologen. AB - A unique multiple diffusion growth chamber, an Ecologen, designed for the study of interactions among microorganisms, was introduced as a means of growing xenic cultures of Entamoeba gingivalis with Crithidia sp. or Yersinia enterocolitica. Entamoeba gingivalis was grown in the central diffusion reservoir of the Ecologen connected to separate growth chambers inoculated with the microorganisms to be evaluated. Growth of the accompanying bacteria in the E. gingivalis compartment was almost completely eliminated, except for sparse Pseudomonas sp. growth. The most vital E. gingivalis cultures were observed when either Crithidia sp. or Y. enterocolitica were added to the Ecologen 48 h prior to the E. gingivalis inoculum. The medium which provided the best growth of the oral protozoan in this system was the new improved E. gingivalis medium containing antibiotics. PMID- 1459787 TI - Dictyocaulus viviparus: isolation and characterization of a recombinant antigen with potential for immunodiagnosis. AB - Crude adult worm antigen of Dictyocaulus viviparus was examined for specific antigens by SDS-PAGE and immunoblotting using sera from cattle experimentally infected with D. viviparus, vaccinated with a normal or a reduced dosage of the commercial lungworm vaccine, and helminth-free cattle. A D. viviparus-specific region M(r) 18,000 was identified and isolated. A lambda ZAP II cDNA expression library consisting of 4.4 x 10(5) recombinant clones (88% of the total number of clones) was constructed from D. viviparus adult worm mRNA. Rabbit antiserum to the M(r) 18,000 antigen was used to screen the cDNA library and eight positive clones were picked and allocated to the same antigenic family by sibling analysis. All clones were subcloned into the plasmid pGEX-2T, and the clone with highest expression yields was expressed as a glutathione S-transferase fusion protein (DvGST3-14) or, after cleavage with thrombin, as pure recombinant parasite protein (Dv3-14). The native parasite antigen encoded by the clone was identified. The immunodiagnostic potential of the recombinant proteins was assessed by immunoblotting. PMID- 1459788 TI - The kinetics of mebendazole binding to Haemonchus contortus tubulin. AB - The kinetics of the binding of mebendazole (MBZ) to tubulin from the third-stage (L3) larvae of the parasitic nematode, Haemonchus contortus, have been characterized. In partially purified preparations, the association of [3H]MBZ to nematode tubulin was rapid, k1 = (2.6 +/- 0.3) x 10(5) M-1 min-1, but dissociation was slow, k-1 = (1.58 +/- 0.02) x 10(-3) min-1. The affinity constant (K(a)) for the interaction, determined by the ratio k1/k-1, was (1.6 +/- 0.2) x 10(8) M-1. Similar results were obtained with crude cytosolic fractions. In equilibrium studies, performed with partially purified nematode tubulin under similar conditions, a K(a) of (5.3 +/- 1.6) x 10(6) M-1 was obtained. The best estimate for the K(a) of the MBZ-nematode tubulin interaction is considered to be the 'kinetic' value determined from the ratio of rate constants. The slow dissociation of MBZ from nematode tubulin, which contrasts with the rapid dissociation of MBZ from mammalian tubulin, supports the hypothesis that the selective toxicity of the benzimidazole anthelmintics results from a difference between the affinities of mammalian and nematode tubulins for these drugs. PMID- 1459789 TI - Selection of Merino sheep for increased and decreased resistance to Haemonchus contortus: peri-parturient effects on faecal egg counts. AB - Peri-parturient worm egg counts were compared in 395 Merino ewes bred for either increased (IRH) or decreased (DRH) resistance to Haemonchus contortus, or from an unselected control flock (CH). Following a 10 month period with no anthelmintic treatment, a rise in egg counts began about 4 weeks before parturition and continued into lactation. At all stages, egg counts were significantly lower in IRH ewes, even those failing to conceive. Before lambing, IRH ewes averaged 263 epg, compared with 1113 epg in CH and 1618 epg in DRH ewes. After 2 weeks of lambing, lactating ewes averaged 1050, 2173 and 3708 epg, respectively, in the three lines. At the end of lambing, egg counts had increased to 1645, 3959 and 4124 epg, respectively. Counts appeared to have peaked in IRH ewes but not in DRH ewes. Ewes with twins had higher counts than those with singles, and ewes suckling lambs had higher counts than those losing lambs. No significant variation was associated with age of ewe (2-7 years). Although there were several nematode species present, the results suggest that, in comparison with DRH ewes, IRH ewes were particularly effective in reducing pasture contamination with H. contortus, both before and during the peri-parturient period. PMID- 1459790 TI - Association of blood eosinophilia with the expression of resistance in Romney lambs to nematodes. AB - The dynamics of blood eosinophilia was studied in Romney lambs dosed twice weekly with 5000 infective larvae of Trichostrongylus colubriformis. A marked rise in blood eosinophil counts of the dosed lambs coincided with the start of the decline of faecal egg counts (FEC). Eosinophilia was also studied in grazing Romney lambs from a breeding programme, based on selection for high or low FEC. Comparison of the sire groups suggested that the magnitude of the eosinophil response was under genetic control. The significant negative correlations between blood eosinophil counts and FECs confirmed the association between eosinophilia and the expression of resistance in Romney lambs to nematodes. However, comparison of the mean blood eosinophil counts and FECs for both the ram and ewe lambs of the resistance sire groups suggested that the association of eosinophilia and resistance may be greater for some sire groups than others. PMID- 1459791 TI - Inflammatory responses in the intestine during tapeworm infections. Mucosal mast cells and mucosal mast cell proteases in Sprague-Dawley rats infected with Hymenolepis diminuta. AB - Comparative studies were made of two populations of Sprague-Dawley rats infected with Hymenolepis diminuta. The time course of infection, the development of mucosal mastocytosis and the levels of rat mucosal mast cell (MMC) protease (RMCP II) in serum and in jejunal mucosal tissues were monitored at intervals after infection with 40 cysticercoids of the tapeworm. Worm expulsion patterns differed markedly between the two populations, rats of New Zealand origin showing an abrupt and clear-cut loss of worms, rats of English origin showing a more gradual decline over a longer time period. In both populations, however, numbers of MMC and levels of tissue RMCP II were positively correlated with time after infection and negatively correlated with worm numbers. In only one of the three experiments (using English strain rats over a short time period) did levels of serum RMCP II change with time. In the other two experiments, in which English-strain and New Zealand-strain rats were used, there were no correlations between serum RMCP II and time, numbers of MMC, numbers of worms or levels of tissue RMCP II. The absence of correlation between serum RMCP II and worm loss in these experiments implies that MMC have no direct role in expulsion of H. diminuta. The data do show, nevertheless, that this purely luminal tapeworm is fully capable of activating the mucosal T lymphocyte-MMC precursor axis to elicit a mucosal mastocytosis. PMID- 1459792 TI - Secondary Echinococcus multilocularis infection in severe combined immunodeficient (scid) mice: biphasic growth of the larval cyst mass. AB - E. multilocularis infection was suppressed in C.B-17 mice after intraperitoneal inoculation of protoscoleces, with larval cysts weighing no more than 1.0 g. In scid mice, which are genetically identical to C.B-17 except for a deficiency in functional lymphocytes, infection progressed and larval cysts reached a mass of 17.5 g at 15 weeks post-infection. The growth of the larval cyst mass in scid mice was similar to that in other susceptible mouse strains, with a biphasic pattern. Histological observations revealed giant cells and granulomatous inflammation in the C.B-17, but not in the scid mice. These results led to the conclusion that suppression of the growth of the larval cyst mass in the initial stage of infection in susceptible mice strains is caused by factors other than the host's lymphocytic immune response. PMID- 1459793 TI - The effect of adjuvant and specific or non-specific vaccination on development of protective immunity of rabbits against Trichostrongylus colubriformis infection. AB - Adult New Zealand rabbits were vaccinated subcutaneously with one dose of 100 micrograms adult nematode phosphate buffered saline-soluble proteins (PBS-ASP, groups I and II), a detergent-soluble fraction of adult somatic proteins (DS-ASP, group III) or three doses of 1 mg normal rabbit serum proteins (group IV). Injections of the immunogens in groups II, III and IV were accompanied with beryllium hydroxide, Be(OH)2 as an adjuvant. Vaccinated rabbits and also those of group V (naive) were challenged orally with 10,000 infective larvae of T. colubriformis 14 days after antigen injection and necropsied 2 weeks later. A single dose of PBS-ASP induced 33.5% protection when the antigen was given alone (group I) and 69.4% when injected with Be(OH)2 (group II). A detergent-soluble fraction of ASP given with the adjuvant provided 87.2% protection (group III), whilst non-specific vaccination with serum proteins plus Be(OH)2 elicited 99% protection (group IV). Mesenteric lymph node leukocyte responses were measured using a leukocyte migration inhibition assay. A significant response was observed only in group IV. In ELISA tests IgA antibodies specific to PBS-ASP reached the highest level in the intestinal mucosa of groups I and II and in the bile of groups I and III. Antibody levels of IgG isotype were similar in the intestinal mucosa of all the immunized groups. Nematode antigen was detected using a 'sandwich' ELISA method in faecal protein extracts of rabbits of groups II and III on days 2-6 after challenge. PMID- 1459794 TI - Population dynamics of Trichostrongylus colubriformis and Ostertagia circumcincta in single and concurrent infections. AB - Twenty-one-week-old worm-free pen-reared lambs were infected weekly with either 10,000 T. colubriformis larvae, 5000 O. circumcincta larvae, or with both species (15,000 larvae per week). Larval establishment and total worm burdens were estimated after 4, 7, 10 and 13 weeks of infection. Faecal egg counts and lamb bodyweights were measured weekly, and numbers of eosinophils in blood were estimated before infection and at weeks 5, 8 and 14. For both species of worms, the dynamics of infection (establishment, worm burdens, egg counts) were not affected by concurrent or pre-existing infection with the other species. Infection with T. colubriformis alone did not protect against O. circumcincta, but infection with O. circumcincta alone provided slight protection against the T. colubriformis larvae. Blood eosinophils increased between 5 and 8 weeks of infection and were similar for the three infections. This corresponded to the reduction in establishment for both species. PMID- 1459797 TI - Tissue-type plasminogen activator and von Willebrand factor plasma levels as markers of endothelial involvement in patients with Raynaud's phenomenon. AB - In order to investigate the significance of high circulating levels of von Willebrand factor (vWF), recently observed in patients with vascular diseases, we compared the plasma levels of vWF with those of tissue-type plasminogen activator (t-PA) and the platelet content of serotonin (5-HT) in 40 patients with Raynaud's phenomenon (RP), primary or associated to systemic sclerosis (SSc), and in 14 patients with chronic peripheral obstructive disease due to arteriosclerosis (PAOD). VWF and t-PA plasma levels were significantly increased (p < 0.001) in SSc (vWF: 158.2, range 116.3-305.0%; t-PA: 10.2, range 6.4-17.8 ng/ml). By contrast, normal plasma levels of both vWF (85.3, range 53.5-157.0%) and t-PA (6.5, range 2.7-9.3 ng/ml) were observed in primary RP. VWF and t-PA were normal in PAOD patients, compared with age-matched healthy controls (vWF: 143.0, range 57.0-204.0%; t-PA: 7.5, range 3.4-13.6, ng/ml). The platelet content of 5-HT was within the normal range (37.3-99.7 ng/10(8) platelets) in RP patients, but significantly reduced (P < 0.05) in PAOD patients (39.0, range 14.7-91.4). Our data suggest that the different pattern of circulating vWF and t-PA between SSc and arteriosclerotic patients may be related to a different endothelial cell involvement. Whether this increase may reflect active attempts of regeneration and repair, indicating endothelial cell viability rather than damage is a matter of speculation. PMID- 1459795 TI - Immunoperoxidase labelling of albumin at the endothelial cell surface of frog mesenteric microvessels. AB - Albumin was visualised at the endothelial cell surface of perfused frog mesenteric microvessels using immuno-peroxidase labelling. Vessels in the mesenteries of pithed frogs were washed free of blood and then perfused with frog Ringer solutions containing bovine serum albumin (BSA) at a concentration of 20 mg BSA ml-1, followed by a brief Ringer flush to remove excess albumin from the vessel lumen. The tissues were fixed in 1% glutaraldehyde and a double antibody labelling technique used to identify albumin within the tissue. A dense layer of peroxidase reaction product was seen, which extended 25-50 nm into the vessel lumen. It appeared as a continuous layer lining the luminal openings of interendothelial cell clefts and vesicles open to the luminal cell surface. In some vessels a more irregular layer of peroxidase labelled albumin was seen extending 150 to 200 nm into the vessel lumen, whilst in others clumps of peroxidase labelled albumin were also seen within the vessel lumen. These data offer direct evidence that BSA does interact with the endothelial cell surface of perfused frog mesenteric microvessels but suggest that a proportion is loosley or non-specifically bound to the cell surface and can be removed by a brief Ringer flush. The remainder appears more tightly bound and resistant to Ringer flush. PMID- 1459796 TI - Subcutaneous interstitial fluid pressure and arm volume in lymphoedema. AB - Interstitial fluid pressures were measured by the wick in needle method in the swollen and normal arms of 38 patients with lymphoedema resulting from treatment for breast cancer. The mean increase in arm volume, calculated from sequential circumferential measurements, was 33% (range 0.25 to 85.9). Subcutis interstitial fluid pressure in the swollen arm (2.0 cmH2O range -4.5 cmH2O to 6.8 cmH2O) was significantly greater (p < 0.001) than in the contralateral, non-swollen arm ( 2.6 cmH2O range -11 cmH2O to 0 cmH2O). Interstitial fluid pressure in the oedematous arm did not correlate with the duration of the swelling (1-324 months), but did correlate with the increase in volume relative to the normal arm (r = 0.38, p < 0.05), the slope ('apparent compliance') being 28 ml.dl-1.cmH2O-1. The pressure-volume curve was less steep than the classic curve for acute oedema of dog limbs (Guyton, 1965). Vascular pressures were normal. The interstitial fluid pressures were not as high as those reported for lymphoedema of the lower extremity (mean 17.9 mmHg, Christensen et al., 1985). Nevertheless, the rise in interstitial fluid pressure by an average of 4.6 cmH2O constitutes a force opposing further microvascular fluid filtration and perhaps promoting fluid drainage out of the arm. PMID- 1459798 TI - Circulatory adaptation to the increased metabolism in the skin at the site of the tuberculin reaction. AB - The sequence of changes at the site of a positive tuberculin test response were studied in 19 healthy young adults who had been immunised with BCG in childhood. The development of erythema preceded that of induration and both were most intense at 48-72 h. The strongest reactions showed higher laser Doppler (LD) flux at the periphery than at the center (central relative slowing). All showed a substantial reduction in steady-state (ss) tcpO2 from 24 h onwards and the oxygen consumption rate (mlO2.kg-1.min-1), calculated from the rate of fall in tcpO2 during temporary cuff occlusion of arterial input, was raised (greater than two fold) throughout the period of study (to 96 h). The density of lymphocytes and macrophages in the inflammatory infiltrate in the dermis was related to the fall in tcpO2.ss and to the extent of thickening of the dermis. These experiments showed that the previously healthy dermal microcirculation can adapt to temporary increase in metabolic demands of leucocytes emigrated from the circulation into the tissue: in intense delayed hypersensitivity (DHS) reactions there is considerable hypoxia and respiratory debt, but maintenance of viability in the short-term. It is likely that similar adaptations occur in the period of establishment of microbial infection. PMID- 1459799 TI - Red cell velocity and microvessel diameter measurement by a two fluorescent tracer method under epifluorescence microscopy: application to cerebral microvessels of cats. AB - Fluorescein isothiocyanate (FITC)-labeled red blood cells (RBCs) and rhodamine-B isothiocyanate (RITC)-labeled dextran were used as two fluorescent tracers under intravital fluorescence microscopy. RBC velocity in cerebral microvessels of cats was measured with a dual window technique using FITC-labeled RBCs as a flow tracer. Measurement of the vessel diameter was performed using a digital image processor system by staining plasma with RITC-labeled dextran. The RBC velocity, obtained directly with digital cross-correlation of videodensitometric signals derived from the two windows, coincided with those obtained with the frame-by frame analysis. The obtained RBC velocity ranged between 12.9 and 0.45 mm/sec in arterioles (< 60 microns) in diameter, 4.2 and 0.18 mm/sec in venules (< 60 microns in diameter), and 1.1 and 0.26 mm/sec in capillaries. The use of the labeled RBCs as the flow tracer enabled us to measure a wide range of RBC velocity (up to about 7 mm/sec) by setting the distance between the two windows beyond about 200 microns. PMID- 1459800 TI - In vivo responses of allografted cerebral parenchymal arterioles to ethanol and angiotensin II: effect of calcium channel blockade. AB - The goals of these studies were to determine: 1) the effect of ethanol and angiotensin II on the diameter of allografted cerebral parenchymal arterioles in vivo, and 2) the effect of the calcium antagonist, verapamil, in modulating the responses of allografted cerebral parenchymal arterioles to ethanol and angiotensin II. Using a chamber technique, neonatal (< 24 hours old) cortical tissue was transplanted onto the cheek pouch of adult hamsters. Eight to thirteen days after allografting, hamsters were anesthetized with sodium pentobarbital (6.0 mg/100 grams i.p.), and allografted cerebral parenchymal arterioles were viewed using intravital microscopy. Diameter of allografted cerebral parenchymal arterioles was measured before (control), during and after topical application of ethanol (0.1%, 0.25%, 0.5%, 1.0%, and 2.0%) and angiotensin II (0.1 and 1.0 ng/ml). Application of ethanol and angiotensin II was repeated after changing the suffusion fluid to one containing verapamil (50 mg/L). We found that ethanol and angiotensin II produced dose-related constriction of allografted cerebral parenchymal arterioles. In addition, verapamil significantly attenuated vasoconstriction produced by ethanol and angiotensin II. Thus, our findings suggest that ethanol and angiotensin II cause constriction of allografted cerebral parenchymal arterioles through a calcium-dependent mechanism. PMID- 1459801 TI - Lessons learned from AIDS education in schools. PMID- 1459802 TI - AIDS-like epidemic: no evidence. PMID- 1459803 TI - ICN/3M scholars: tomorrow's nursing leaders. AB - For over 20 years ICN and the Minnesota Mining and Manufacturing Company (3M) have sponsored a scholarship programme directed toward helping nurses further their education in nursing. Since then 48 nurses have been provided the needed funds to reach their professional goals and subsequently to help answer their country's healthcare needs. Their degrees and expertise have opened up professional doors but most of all have given them the confidence to become driving forces in initiating research and other programmes that aim to provide quality care to all their countries' citizens. PMID- 1459804 TI - Nursing in Africa today. AB - In any description of nursing in Africa, one must consider the continent's vast size and complexity of cultures. Even the concept of nursing does not have the same meaning in all African countries. Below, Osei-Boateng updates the status of African nurses, derived from her paper that appeared in the 10th anniversary brochure of the West African College of Nursing (WACN). To simplify the analysis, she focuses only on the region south of the Sahara--excluding South Africa--in her overview of the slow progress and vast education needs of nurses caught in the web of their countries' socioeconomic and political chaos ... and lethargy. PMID- 1459805 TI - A unique concept of nursing care. AB - The form of caring may vary across cultures; but the perception of the caring by the receiver is universal. The patient knows what hurts, what problems are crucial and what experiences have been deeply buried. As a Chinese from Taiwan, raised in Japan and educated in the US, the author provides a unique concept of nursing care that relies on the patient for direction. PMID- 1459806 TI - Participatory research: getting the community involved in health development. AB - The Alma Ata Declaration states that "the people have the right and duty to participate individually and collectively in the planning and implementation of their health care." This means that community involvement in health development is fundamental in the battle for health. And, as the author demonstrates below, its participation in health research is necessary in the process of finding better ways and methods to provide health for all. PMID- 1459807 TI - Xanthofibroma of the adrenal gland. AB - The authors report on a 43-year-old woman who had undergone unilateral adrenalectomy for a right suprarenal mass. The removed specimen was histopathologically defined as xanthofibroma, a hitherto unpublished adrenal tumour. The connective tissue protein of this rare tumour contained great amounts of collagen, non-collagenous protein and elastin. The significance of such abnormal proliferation of fibrous tissue and the conventional sonographic and CT features of this neoplasm are discussed. PMID- 1459808 TI - Inverted papilloma of the renal pelvis. AB - The authors describe a case of inverted papilloma. It is relatively rare and generally appears as a benign tumour. PMID- 1459809 TI - Multiple fibroepithelial polyps of the renal pelvis and calyces: a case report. AB - Fibroepithelial polyp of the renal pelvis is an extremely rare entity. We report a case of multiple fibroepithelial polyps of the renal pelvis and calyces and discuss this rare and confusing condition with its clinical, radiological and pathological findings. PMID- 1459810 TI - Usefulness of non-invasive diagnostic methods for early detection of neoplasms of the urinary tract and male genitals among workers of the Mazovian Refining and Petrochemical Plant in Plock. AB - The studies were aimed at the evaluation of the usefulness of non-invasive diagnostic methods including inquiry, clinical examination, transabdominal ultrasonography, cytologic examination of the urinary sediment, determination of blood serum concentrations of certain neoplastic markers, and urinalysis for early detection of neoplasms of the urinary tract and male genitals; and at the determination of the sensitivity and specificity of percutaneous ultrasonography combined with cytologic examination of the urinary sediment for detection of neoplasms of the kidneys and urinary tract, particularly of the urinary bladder. Urological examinations were performed in 300 workers occupationally exposed to oil derivatives. Neoplasms of the urinary tract and male genitals were detected in 37 (12.3%) workers. Neoplasms of the urinary bladder were found most frequently. They were diagnosed by non-invasive methods in 14 (4.7%) and verified clinically and histologically in 11 (3.7%) persons. The results seem to indicate the usefulness of non-invasive diagnostic methods for urological screening studies among occupational populations with increased risk of neoplasms of the urinary system and male genitals. The high sensitivity (93%) and high positive predictive coefficient (0.90) for the combination of transabdominal ultrasonography and cytological examination of the urinary sediment for detection of urinary system neoplasms seem to be tokens of their high diagnostic value and clinical usefulness. PMID- 1459811 TI - In situ prone ESWL for the treatment of lower ureteral stones: experience with 28 patients. AB - Twenty-eight patients with lower ureteral stones underwent in situ extracorporeal shock wave lithotripsy (ESWL) in the prone position over the period of 7 months between March 1990 and September 1990. For stone disintegration the spark gap shock wave lithotripter Tripter XI (Direx) was used. Satisfactory disintegration was achieved in 93 per cent of patients. The stone-free rate at 12 weeks was 82 per cent, and 11 per cent had residual fragments less than or equal to 4 mm in diameter. Twenty-one per cent of patients required repeat treatments. For only 2 patients general anaesthesia was required (7 per cent). There were no remarkable complications except for haemospermia which resolved spontaneously 15 days after treatment. It was concluded that in situ prone ESWL is an effective and safe procedure for the treatment of lower ureteral stones. PMID- 1459812 TI - Fifty years of antireflux ureterovesicoplasty. AB - In spite of the impressive progress in medical science, surgery remains an empirical skill. Surgery of the ureterovesical junction is a permanent challenge for all generations of urologists. Half a century of intensive development of modern surgery evidences the efforts to reestablish function by a perfect copy of natural anatomy. PMID- 1459813 TI - The permanent ureterocutaneostomy (UCST). AB - During a period of eleven years, ureterocutaneostomy (UCST) as a permanent urinary diversion was performed in 44 highly selected patients. Postoperative complications, in particular stenoses or strictures, can be avoided if subtle operative techniques are applied. Ureterocutaneostomy, which is functionally similar to an incontinent ileal conduit, turns out reasonable especially as a palliative procedure in patients with unresectable pelvic mass, dilated ureter, or solitary kidney. Thus, the authors conclude that UCST as a permanent urinary diversion still has to be considered valuable in a highly selected group of patients. PMID- 1459814 TI - Bladder leiomyosarcoma: report of three cases. AB - Three patients with leiomyosarcoma of the urinary bladder are presented. One case showed urothelial carcinoma in situ also. The mode of presentation and operative findings were similar in two female patients, whereas the lesion seemed to be more aggressive in a male patient. PMID- 1459815 TI - Percutaneous drainage of prostatic abscess. AB - The treatment results of 2 patients with prostatic abscess who underwent perineal percutaneous drainage under transrectal ultrasonographic guidance are described. Both patients were treated definitely and without complications. It is concluded that the use of transrectal ultrasound during the procedure increases the effectivity and safety of treatment. PMID- 1459816 TI - Prostatectomy in the very aged. AB - The number of very aged men who demand prostatectomy for benign disease is increasing. We have assessed surgery results in 79 patients operated during the last four years. Sixty-two underwent endoscopic and 17 open procedure. Mortality rate was 3.7%. Two patients died in the first week and one patient three weeks after surgery. Morbidity rate was 61% but did not significantly affect the final operative outcome. Operative success rate six weeks postoperatively was 87%, satisfactory for this age group. After detailed preoperative evaluation and postoperative care by specialized age care team, prostatectomy is safe, effective and involves low-cost treatment. PMID- 1459817 TI - Prognostic variables in patients with prostate cancer: influence of blood group ABO (H), the Rhesus system, age, differentiation, tumour stage and metastases. AB - Among 279 patients with carcinoma of the prostate no relationship was observed in survival between blood groups ABO (H) or the rhesus system. Age at diagnosis is relevant for the outcome of the disease, but grade of differentiation, tumour stage and metastases are more important predictors of survival. PMID- 1459818 TI - Update of experience in the treatment of localized carcinoma of the prostate by definitive external irradiation. AB - In 1987 a retrospective analysis was performed of 116 patients with carcinoma of the prostate localized to the pelvis who were treated by radiotherapy at the Northern Israel Oncology Center during the period between 1977 and 1982. It was shown that definitive external beam irradiation is an effective, simple, and easy treatment modality for localized prostatic cancer. PMID- 1459819 TI - Psychosomatic evaluation of patients with congenital penile deviation. A postoperative catamnestic follow-up. AB - Thirty-three patients with congenital penile deviation were examined by a semi structured interview and psychodiagnostic tests (Giessen test, Giessen complaint sheet) prior to undergoing surgery according to the Nesbit-Kelami technique. A prognosis was then made to determine the extent to which the problems and disturbances reported by the patient or uncovered by the examiner could be improved by the operation. This prognostic assessment was then verified in a subsequent catamnestic examination (N = 20), at an average of 21.3 months after the intervention. An attempt is made to identify and define preoperative indicators that permit to predict the postoperative course. PMID- 1459820 TI - Prostaglandin E2 in renal transplant recipients. AB - The concentrations of prostaglandin E2 (PGE2), sodium, potassium and creatinine were determined in the blood and urine of 50 renal transplant recipients treated with cyclosporine A or azathioprine, as immunosuppressive agents, for at least one year post transplantation. Fourteen healthy subjects served as control group. The urinary PGE2 excretion was significantly decreased in all treated renal transplant recipients and this reduction was associated with significant decrease in urinary excretion of sodium and potassium. On the other hand, a high elevation in blood PGE2 concentration was observed while no significant changes were seen in sodium and potassium levels in the blood of these renal transplant recipients. The observations suggest an association between urinary PGE2 reduction and immunosuppressive treatments in renal transplant recipients; also, PGE2 may regulate intra-renal haemodynamics and influence the renal tubular electrolyte excretion. Moreover, urinary PGE2 can be used as an indicator of successful renal transplantation. PMID- 1459821 TI - Vitamin B6 requirements in chronic renal failure. AB - According to our results the long-term daily oral supplementation of 6 mg vitamin B6 was sufficient for prevention of vitamin B6 deficiency in chronic renal failure, regular dialysis treatment and CAPD groups of patients. Haemodialysis and charcoal haemoperfusion have led to non-significant decrease of erythrocyte vitamin B6. A favourable effect was found of daily oral administration of 50 mg pyridoxine on electrophoretic mobility of peripheral blood lymphocytes and cellular immunity. PMID- 1459823 TI - Spontaneous peripelvic extravasation of urine. AB - Spontaneous peripelvic extravasation of urine is relatively uncommon. We experienced 11 cases of spontaneous peripelvic extravasation. Urinary obstruction was caused by calculi in 9 cases, invasion by sigmoid carcinoma in 1 case and ureteral tumour (transitional cell carcinoma) in 1. Six patients presented with signs of peritonitis and 4 out of 9 with calculus did not develop microhaematuria. It is important to differentiate peripelvic extravasation from other acute abdominal conditions. We must pay special attention to patients with signs of peritonitis and normal urinalysis. PMID- 1459822 TI - Laparoscopic surgery in urology. AB - In recent months, laparoscopy has been used for such urological procedures as varicocelectomy, pelvic lymph node dissection and even nephrectomy. It would appear that laparoscopic surgery is going to make an important contribution to the field of endourology. In order to assess the current status and value of laparoscopic techniques to urologists, we have reviewed the history of laparoscopy in general and urologic laparoscopy in particular. PMID- 1459824 TI - Urinary tuberculosis: experience of a teaching hospital in Syria. AB - This study was designed to show our experience of urinary tuberculosis in one of the large teaching hospitals in Syria. It was a prospective study involving 48 patients (29 males and 19 females) with confirmed tuberculous lesions in the urinary tract. The study period was between 1982-1987. The presenting symptoms were protean, and there were often delays between onset of symptoms and eventual diagnosis. The highest age incidence was in the second and fourth decades. Beside the suggestive clinical manifestations, final diagnosis was reached by various means. Repeated examinations of EMU smears were positive in about 20% of cases. Urine culture was positive in 33.3%, while varied percentage of cases showed some radiological changes suggestive of tuberculosis. Other investigations included cystoscopy and biopsy of suspected lesions. Treatment was conservative by chemotherapy in 45% of cases, with complete recovery in about 33%, while acceptable results were shown in congruent to 19%, and failure of treatment or recurrence of active disease in 48% of cases. Some forms of surgical intervention were carried out in 55% of patients. Cure was seen in 50% of them, while 25% had acceptable results and failure was shown in the remaining 25%. It is concluded that urinary tuberculosis remains an important infectious disease problem in our country. The high rate of failure of both medical or surgical treatment is mainly due to late diagnosis. PMID- 1459825 TI - Experience with the Direx Tripter X-1 shock-wave lithotripter. AB - The authors give account of the experience they gained with the Direx Tripter X-1 (ESWL) apparatus. In a random material they succeeded to render 81.5% of the patients stone free within three months. They judge the apparatus suitable for in situ treatment of pelvic and ureteric stones and for the monotherapy of staghorn calculi. It is easy to handle, inexpensive to buy and maintain but noisy to operate, moreover the patient has to be anaesthetized. All in all it is highly useful in the treatment of renal lithiasis. PMID- 1459826 TI - Late development of pelviureteric junction obstruction (PUJO) in a girl with previously normal pyelogram: a case report. AB - A case of ureteropelvic junction obstruction in a girl with previously normal pyelogram is presented. The aetiology of this development is unclear but this report emphasizes the need for a close follow-up of patients with persistent flank pain even if the initial pyelograms are normal. PMID- 1459827 TI - Transurethral ultrasonography, fiberoptic cystoscopy and bladder washout cytology in the evaluation of bladder tumours. AB - The impact of transurethral ultrasonography, fiberoptic cystoscopy and bladder washout cytology on assessment of bladder tumours was investigated in this study. Transurethral ultrasonography had an accuracy rate of 96.5% in diagnosing and staging bladder tumours. The accuracy rates of fiberoptic cystoscopy and washout cytology were 90.9% and 73.7%, respectively, in diagnosis. The efficacy of transurethral ultrasonography was found to be high enough for routine employment in the evaluation of the bladder tumours. Fiberoptic cystoscopy in conjunction with washout cytology as a combination relatively easy to perform can be used especially for follow-up purposes of the bladder tumours. PMID- 1459828 TI - Terodiline in the treatment of nocturnal enuresis in children. AB - The effect of terodiline was investigated in 17 children with nocturnal enuresis. Twelve of them were evaluated urodynamically before treatment and 6 of these were proved to have detrusor instability with or without provocation. Terodiline in a daily dose of 12.5 mg was administered for 4 weeks. After treatment the number of wet nights per week has significantly decreased. Urodynamically, maximum cystometric capacity has statistically increased and in 2 patients involuntary contraction has disappeared. During these periods no serious side effects were encountered. Terodiline could improve urodynamic parameters in nocturnal enuresis. These changes appear to be favourable in clinical improvement. PMID- 1459830 TI - Positron emission tomography in the study of acute radiation effects on renal blood flow in dogs. AB - Renal blood flow measurements have been carried out by means of positron emission tomography (PET) to facilitate the detection of radiation-induced injuries. The advantages of the method employed in animal experiments are described. PMID- 1459829 TI - Primary lymphoma of the penis with rationale of treatment. AB - Appropriate care of a patient with primary lymphoma of the penis requires consideration of the diagnoses, thorough evaluation, and knowledge of the various therapeutic approaches. A patient is presented with brief review of similar cases together with the rationale for the use of radiation therapy and chemotherapy rather than surgery. PMID- 1459832 TI - The variety of clinical and histopathologic presentations of glomerulonephritis associated with latent syphilis. AB - Glomerulonephritis is a well established but rather uncommon complication of latent secondary syphilis. We present three cases of glomerulopathies associated with luetic infection, observed and managed in our institutions in the past three years. They illustrate a variety of clinicopathologic presentations of this nephropathy, from acute nephrotic syndrome through membranous glomerulopathy up to rapidly progressive glomerulonephritis. Regardless of the clinical course and histologic type, they were all characterized by strongly positive results of serologic tests for syphilis. Our observations suggest the necessity of eliminating luetic infection in aetiologic considerations of each newly diagnosed case of nephrotic syndrome. PMID- 1459831 TI - Central catecholamine, sympathetic nerve and vascular protein in the acute phase of two-kidney, one-clip renovascular hypertension in rats. AB - Incorporation of 3H-proline into the non-collagenous protein in mesenteric arteries in two-kidney, one-clip hypertensive rats was greater than that in normotensive rats. Splanchnicotomy predominantly over the root of mesenteric arteries or intracranioventricular injection of 6-hydroxydopamine prevented the development of hypertension in 2K-1C rats concomitant with the reduction of incorporation of 3H-proline into the non-collagenous protein in mesenteric arteries. The content of norepinephrine in the hypothalamus in 2K-1C rats was lower than that in normotensive control rats. These findings indicate that increased non-collagenous protein synthesis in mesenteric arteries or low level of hypothalamic norepinephrine has facilitative effects on the development of 2K 1C hypertension. PMID- 1459833 TI - Calcium blockers enhance cisplatin-induced nephrotoxicity in rats. AB - To examine the effects of calcium blockers on nephrotoxicity caused by cisplatin, the renal function and renal accumulation of Pt in Sprague-Dawley rats given 6.5 mg/kg i.v. cisplatin simultaneously with several doses of verapamil or nicardipine were evaluated. BUN, serum creatinine and kidney Pt concentrations in rats given more than 5.0 mg/kg of verapamil were significantly higher than those of the control animals injected with 6.5 mg/kg i.v. cisplatin alone, and the increase of each value was dependent upon the dose of verapamil. BUN, creatinine and kidney Pt in rats injected with more than 0.5 mg/kg i.p. nicardipine were also significantly higher than those of the controls. Calcium blockers enhanced the renal accumulation of Pt and the nephrotoxicity of cisplatin. PMID- 1459834 TI - Influence of prostacyclin infusion on haemodialysis efficiency and blood cells. AB - Dialysis efficiency, platelet and leukocyte counts, as well as malonyldialdehyde (MDA) level and lactate dehydrogenase (LDH) activity in serum were assessed in 10 patients (8 males, 2 females, aged 28-58 years) treated with repeated haemodialysis due to terminal renal failure. Patients were examined twice: during a 4-hour haemodialysis in the presence of heparin as the anticoagulant, and a week later in the course of another haemodialysis combined with infusion of heparin and prostacyclin. Statistically significant lower level of urea at the end of dialysis and significantly higher urea clearance were found during haemodialysis with prostacyclin-heparin infusion in comparison with infusion of heparin alone. As compared with the initial values obtained prior to dialysis, neutropenia and thrombocytopenia were observed during haemodialysis with heparin alone but the counts remained generally unaltered when both prostacyclin and heparin were administered. During and after haemodialysis with heparin and prostacyclin both MDA level and LDH activity were lower than in case of haemodialysis with heparin alone. PMID- 1459836 TI - CAPD versus haemodialysis: a comparison in the same patients. AB - Most studies comparing CAPD and haemodialysis (HD) were done in different populations, matched for sex and age. The present report compared 13 non-diabetic end-stage renal failure patients who were treated for at least six months with each type of therapy. Analysis of the data revealed a higher haemoglobin during CAPD but no differences in the blood transfusion requirements. Serum creatinine, BUN and potassium were lower during CAPD and serum calcium was higher during HD. Serum cholesterol levels were higher during CAPD and returned to pre-CAPD levels during the fourth month after being transferred to HD. Hospitalization rates were similar with the two treatments. Our study confirmed previous sex- and age matched studies comparing CAPD and HD therapy. PMID- 1459837 TI - The killing of four therapists in the West Jerusalem Mental Health Center. PMID- 1459835 TI - Peritoneal dialysis in Hungary. AB - In 1991 the technical conditions and the number of patients receiving peritoneal dialysis were surveyed in the Hungarian nephrology and dialysing units. Not only the number of patients with chronic uraemia (undergoing dialysis + transplantation) is lower in this country as compared to the European average (106 and 236 per one million people, respectively), but also their distribution according to the type of treatment is different. For several years patients under intermittent peritoneal dialysis make up more than 10% of the cases and those under continuous ambulatory peritoneal dialysis less than 2% (in Europe: < 2% and 4-43%, respectively). The survey also included the types of solution, disinfection and connecting devices used in peritoneal dialysis, as well as the incidence of peritonitis and the administration of antibiotics. The principles of biocompatibility, the function of interleukin, as well as the effectiveness and the conditions of continuous ambulatory peritoneal dialysis are summarized. PMID- 1459838 TI - Adjustment problems among Soviet immigrants at risk. Part I: Reaching out to members of the "1000 families" organization. AB - An outreach, preventive mental health project with Soviet immigrants implemented during and immediately following the Gulf War is described. One hundred and fifty immigrant families were visited by immigrant mental health professionals when the level and nature of their psychological distress was assessed. In the analyses of data, patterns of distress over time and factors which contributed to psychological distress were also examined. The main finding of the study concerned the subjects' well-being which was found to be marginally related to the Gulf War. Furthermore, no post-traumatic reactions could be discerned. Instead, immigration related factors, both emotional and objective, were correlated with the psychological distress of the subjects. PMID- 1459839 TI - The psychological profile of Jewish late adolescents in the USSR: a pre immigration study. AB - Psychological well-being and the level of psychological autonomy were studied in a group of 109 Jewish late adolescents in the USSR. The subjects were not found to be more distressed than their American peers, but their dependency on their parents was significantly higher. The findings are discussed in the light of Soviet social values and child rearing attitudes and their impact on the adjustment of Soviet immigrant adolescents in Israel. PMID- 1459840 TI - Clinicians' assessments of suicide risk: can self-report measures replace the experts? AB - This study examined the possibility of using standardized self-report measures as "stand-ins" for clinicians' assessments of suicide risk. Subjects were 252 new applicants to a military mental health clinic who completed a battery of questionnaires and underwent clinical interviews. The self-report measures of psychiatric symptomatology (general and depression), personality (impulsivity, anger), and cognitions (hopelessness, attitudes toward life and death) were not highly correlated with clinicians' assessments of suicide risk and some showed a non-linear association. These findings suggest that the two methods of assessment are not interchangeable and that clinicians base their assessments of suicide risk, at least in part, on factors not assessed by the above questionnaires. PMID- 1459841 TI - Program and process: designing the physical space of a day hospital. AB - Programmatic changes in the delivery of mental health services demand a reevaluation of the space devoted to those services. A growing body of mental health literature has been reported concerning the need to involve multidisciplinary teams in the design of mental health facilities. The development of Day Hospitalization Units offers a team the professional challenge of dealing with the physical environment. The following case study describes a given physical space and the process of change therein; based on this study and other relevant examples, we will discuss the relationship between physical space and the process of change. PMID- 1459842 TI - Traffic accident injuries of children: the need for prospective studies of psychiatric sequelae. AB - This paper presents a literature review of epidemiological data relevant to traffic accidents of children, including their personality and behavioral predisposition, social factors, association with risk taking behavior, rehabilitation, and incidence of post traumatic stress syndrome. The need for prospective studies of psychiatric sequelae of such accidents is highlighted. Three case vignettes are presented. PMID- 1459843 TI - Is there a place for paradoxical "maneuvers" in conventional psychotherapy? AB - This paper reviews the literature concerning the use and theoretical background of paradoxical maneuvers in conventional psychotherapy. By demonstrating a clinical example we highlight the usefulness of such an approach and the necessity for further research in finding valid indications and contraindications for its use. PMID- 1459844 TI - Federal policy on forgoing treatment or care: contradictions or consistency? PMID- 1459845 TI - The case for euthanasia: a humanistic perspective. PMID- 1459846 TI - Once more unto the breach: the right to die--again. PMID- 1459847 TI - Altruistic humanism and voluntary beneficent euthanasia. PMID- 1459848 TI - Voluntary active euthanasia: the next frontier? PMID- 1459849 TI - Voluntary active euthanasia: the next frontier. Impact on the indigent. PMID- 1459850 TI - State v. McKown. PMID- 1459851 TI - Werth v. Taylor. PMID- 1459852 TI - Nutrition and hydration: moral and pastoral reflections. Committee for Pro-Life Activities National Conference of Catholic Bishops April 1992. PMID- 1459854 TI - Hawaii no ka oi in terms of health care. PMID- 1459853 TI - The right to die: an up-date on the law. PMID- 1459855 TI - Evolutionary patterns in chromosome numbers in neotropical Lepidoptera. I. Chromosomes of the Heliconiini (family Nymphalidae: subfamily Nymphalinae). AB - Chromosome counts in meiotic metaphase plates in the gonads of 67 of the probable 68 species of mimetic neotropical heliconian butterflies (Nymphalidae), representing 1524 individuals in 617 subspecies and geographically separate populations from southern Texas to northern Argentina, revealed a consistent haploid number of n = 21 in the genus Heliconius (except for the most advanced species with n = 33, 37, 56, and 60) and n = 31 in the more primitive genera (Eueides, Dryas, Dryadula, Agraulis, and Dione), with a transitional genus (Neruda) showing three species with n = 28-32, 21-22 + 5-10 "microchromosomes", and 20-22 + 1-5 "microchromosomes". The genus Laparus, with a single polymorphic species doris, probably an offshoot of early Heliconius, shows wide karyotypic variation (n = 20-30, 38) sometimes even within a single individual. The two most primitive genera also show much variation: Podotricha has two species with n = 9 and n = 26-29; and Philaethria shows many phenotypically similar species, two with n = 29 and a still uncertain number (at least 3) with n = 88 (most common), 67-72 (most widespread), 62 (very restricted geographically), 52, 21, and 12. Several interspecific hybrids (Heliconius cydno x H. melpomene) showed normal chromosome pairing, while deficient pairing was seen in intersubspecific hybrids in Eueides tales and Heliconius sara. The importance of these results in the evolutionary study of polytypic tropical species is discussed. PMID- 1459856 TI - Putative fragile sites in the horse karyotype. AB - After fluorouracil/5-bromodeoxyuridine synchronization and subsequent FPG staining, the karyotype of 15 phenotypically normal horses displayed several breaks and gaps. Twelve bands 1q24, 4p12, 8q23, 11p12, 16q21, 17q21, 23q31, 23q32, Xp21, Xq22, Xq25 and Xq27 showed relatively frequent fragility. After thymidine/cytidine synchronization and subsequent GWL-banding the same horses display karyotypes without any fragility. Hence it is suggested that the above listed bands harbour folate and/or 5-bromodeoxyuridine sensitive fragile sites. PMID- 1459857 TI - Frequency of multiple insemination in a natural population of Drosophila montana. AB - The frequency of multiple insemination was studied in a boreal Drosophila montana population using mother-offspring data for a sex-linked allozyme locus. Mating with respect to the marker studied was random. In crowded laboratory cultures the heterozygous offspring had higher viability than homozygotes, but no deviations from Hardy-Weinberg proportions were found in natural populations. In multiply sired progenies the males did not contribute equally to the progeny, but the proportion sired by the second male was 0.76. The estimated frequency of multiple inseminated females was 1.19 +/- 0.31, indicating that practically all the females carried sperm of at least two males. The estimate is the largest ever reported in natural populations of Drosophila. However, the interspecific comparisons may not be relevant, because the frequency of multiple insemination does not necessarily reflect the real lifetime frequency of multiple matings. The effects of local ecology and life history characters, e.g., the uniform age structure and the temporal patterning of matings, on the high degree of detected multiple inseminations are discussed. PMID- 1459858 TI - Effects of genetic and environmental factors on the a-b, b-c and c-d interdigital ridge counts. AB - A study of 100 MZ (55 female and 45 male) and 97 DZ (50 male and 47 female) same sexed twin pairs was carried out to analyse the genetic component of the variance of the a-b, b-c and c-d interdigital ridge counts by means of the Christian method. Especially for the a-b interdigital ridge count, we found it important to analyse both sexes separately. Our results suggest that the a-b count in males seems to be more influenced by environmental factors than the other counts. For females, the three interdigital counts seem to have a strong genetic component influencing their phenotypic expression. Factor analysis with VARIMAX rotation showed each interdigital ridge count to be genetically independent. PMID- 1459859 TI - Identification of a hemA gene from Synechocystis by complementation of an E. coli hemA mutant. PMID- 1459860 TI - The expression of parathyroid hormone-related protein (PTHrP) in normal parathyroid: histochemistry and in situ hybridization. AB - The expression and localization of parathyroid hormone-related protein (PTHrP), a major factor responsible for humoral hypercalcemia of malignancy (HHM), was investigated in 14 cases of surgically resected normal parathyroid glands. For light microscopic immunohistochemistry, formalin-fixed and paraffin-embedded specimens were stained with avidin-biotin-peroxidase complex (ABC) using the anti PTHrP monoclonal antibody (MoAb), 4B3. Four percent paraformaldehyde (PFA)-fixed and OCT compound-embedded specimens were used for pre-embedded immunoelectron microscopy. For in situ hybridization, 4% PFA-fixed, frozen sections were studied using a bromodeoxyuridine (BrdU)-labeled PTHrP cDNA probe. Immunohistochemically, 12 of the 14 cases were positive for PTHrP, which was observed mainly in the oxyphil and transitional oxyphil cells. The chief and clear cells, on the other hand, were faintly positive. Electron microscopically, secretory granules positive for PTHrP were observed in cells containing abundant mitochondria. Consistent with the PTHrP immunoreactivity, transcripts of PTHrP were observed also in the oxyphilic cells by in situ hybridization. Thus the production and secretion of PTHrP was shown by the oxyphil cell lineage in the normal parathyroid glands. PMID- 1459861 TI - Comparison of 35S- and digoxigenin-labeled RNA and oligonucleotide probes for in situ hybridization. Expression of mRNA of the seminal vesicle secretion protein II and androgen receptor genes in the rat prostate. AB - The sensitivity of radiolabeled and digoxigenin-labeled RNA probes and synthetic oligonucleotide probes for the detection of seminal vesicle secretion protein II (SVS II) and androgen receptor (AR) mRNA was compared by in situ hybridization in paraformaldehyde-fixed cryostat sections of the rat prostate. Both genes are expressed in different amounts in the various prostatic lobes and contiguous glands. SVS II or AR RNA probes were either labeled with digoxigenin-11-UTP or [35S]UTP by in vitro transcription. A synthetic SVS II oligonucleotide probe was 3' end-labeled (tailed) with either digoxigenin-11-dUTP or [35S]dATP. Hybridized 35S-labeled probes were detected by autoradiography and digoxigenin-labeled probes by immunohistochemistry using alkaline phosphatase conjugated anti digoxigenin antibody or gold-labeled antibody followed by protein A-gold and silver enhancement. Digoxigenin-labeled probes provided the same degree of sensitivity as their 35S-labeled counterparts for the detection by in situ hybridization of weakly and strongly expressed mRNA. Using both labeling methods, the SVS II RNA probes were more sensitive than the oligonucleotide probes and background labelling of the 35S-labeled oligonucleotide probe was high. The digoxigenin method produced less background with all probe types, hybridization signals showed higher resolution and results were obtained faster than with radiolabeled probes. The immunogold silver enhancement system provided the fastest detection of digoxigenin-labeled probes with a sensitivity and resolution similar to that provided by alkaline phosphatase anti-digoxigenin immunohistochemistry. It is concluded that digoxigenin probe labeling and detection provides a sensitive, reliable, and efficient alternative to radiolabeled probes for in situ hybridization of mRNA. PMID- 1459862 TI - Versatility of anti-horseradish peroxidase antibody-gold complexes for cytochemistry and in situ hybridization: preparation and application of soluble complexes with streptavidin-peroxidase conjugates and biotinylated antibodies. AB - In previous studies we have employed a gold-labelled, affinity-purified polyclonal antibody against horseradish peroxidase (anti-HRP--gold) in the avidin biotin peroxidase complex (ABC) technique and indirect labelled avidin-biotin methods. The gold-labelled antibody was used as final revealing reagent to replace the 3,3'-diaminobenzidine (DAB) reaction by immunogold silver staining. The anti-HRP--gold reagent proved to be advantageous since blocking of endogenous peroxidase activity in the tissue sections was not further required and staining of superior contrast and resolution could be achieved in paraffin sections. In the present study we have optimized this technique by combining the last two incubation steps, i.e. HRP-conjugated streptavidin and anti-HRP--gold. Different ratios of the two reagents were tested empirically to establish the conditions for the formation of a soluble complex with optimal staining properties. Quantitative evaluation by densitometry of the staining intensity showed that the soluble streptavidin-HRP/anti-HRP--gold complex and the indirect labelled avidin biotin method employing the gold-labelled anti-HRP antibody performed equally well. Thus, the availability of this complex simplifies the streptavidin-biotin immunogold technique for immunohistochemistry, lectin histochemistry and in situ hybridization and further demonstrates the versatility of anti-HRP--gold complexes. PMID- 1459863 TI - Identification of brush cells in the alimentary and respiratory system by antibodies to villin and fimbrin. AB - Brush cells represent a population of epithelial cells with unknown function, which are scattered throughout the epithelial lining of both the respiratory system and the alimentary system. These cells are reliably distinguished from other epithelial cells only at the ultrastructural level by the presence of an apical tuft of stiff microvilli and extremely long microvillar rootlets that may project down to the perinuclear space. In the present study we show that brush cells can be identified in tissue sections even at the light microscopic level by immunostaining with antibodies against villin and fimbrin, two proteins that crosslink actin filaments to form bundles. In brush cells, villin and fimbrin are not only present in the actin filament core bundles of apical microvilli and their long rootlets but, in addition, both proteins are also associated with microvilli extending from the basolateral cell surface of the brush cells. Basolateral immunostaining specific for villin and fimbrin does not occur in any other epithelial cell type of the respiratory and alimentary tract. Thus immunostaining with antibodies against both proteins allows unequivocal identification of individual brush cells even in sectional planes that do not contain the brightly stained apical tuft of microvilli and their long rootlets. PMID- 1459864 TI - Neuron-specific enolase-like immunoreactivity in the vertebrate retina: selective labelling of Muller cells in Anura. AB - Neuron-specific enolase (NSE) immunocytochemistry was carried out in retinae of goldfish, axolotl, clawed frog, cane toad, lizard, chick, guinea-pig, rabbit, rat, cat and human. With the exception of Anura, strong immunoreactivity was seen in the large ganglion, amacrine cells and horizontal cells of the retina in all of the other species. Photoreceptors were found to be labelled in the rat and human retina and only one cone type in rabbit. Photoreceptor pedicles and ellipsoids were stained in the goldfish and the somata and inner segments of some photoreceptors in axolotl. In the axolotl retina, besides neurons, Muller cells (MCs) were also immunolabelled. In the retina of the cane toad and the clawed frog MCs were the only stained elements. Similarly in other parts of the central nervous system of the cane toad, glial elements of the optic tectum and spinal cord were immunoreactive. In contrast, in the peripheral nervous system, neurons of the 1st sympathetic ganglion and the 2nd dorsal root ganglion were labelled. In double-labelling experiments, glial fibrillary acidic protein and NSE showed colocalisation both in the glial elements of the optic tectum and spinal cord and in MCs of the retina of the cane toad. PMID- 1459866 TI - Does ex vivo labelling of proliferating cells in colonic and vaginal mucosa reflect the S-phase fraction in vivo? AB - The ex vivo labelling of DNA-synthesizing epithelial cells in colonic and vaginal mucosa was compared with in vivo labelling. For this purpose, in vivo S-phase cells were labelled with [3H]thymidine (Tdr) and ex vivo labelling was continued by culturing tissue specimens in bromodeoxyuridine (BrdU). Various methods of tissue culture were employed in order to improve diffusion of medium (and BrdU) in the tissue. BrdU and 3H-TdR labelling were evaluated by immunohistochemistry and autoradiography respectively. Ex vivo labelling resulted in a patchy distribution of labelled cells, which did not correspond with the 3H-TdR labelling pattern obtained in vivo. Under the described conditions ex vivo labelling does not appear to be a reliable for estimation of the proliferative activities in vivo. PMID- 1459865 TI - Patching and capping of LFA-1 molecules on human lymphocytes. AB - The distribution and dynamics of LFA-1 molecules over the surface of human lymphocytes were analysed using immunogold label-fracture and fracture-flip methods. Patching and capping were induced by incubation at 37 degrees C with antibodies directed against the alpha and beta chains respectively of the heterodimeric LFA-1 molecule, and were followed by immunofluorescence. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) to link LFA-1 molecules to the cytoskeleton increased the percentage of capped cells, implying a faster and more efficient process of capping. At all times of clustering or upon phorbol ester treatment, the concentration of LFA-1 in patches and then in caps was not accompanied by a parallel concentration of membrane particles on the freeze fractured plasma membranes. Our results support the role of the cytoskeleton in regulating the capping phenomenon and in controlling the structural organization of the plasma membranes. PMID- 1459867 TI - Vimentin antibodies stain membranous epithelial cells in the rabbit bronchus associated lymphoid tissue (BALT). AB - The lymphoepithelium covering the bronchus-associated lymphoid tissue (BALT) of the rabbit lung was studied with monoclonal antibodies against vimentin, using the indirect immunoperoxidase technique. In the lymphoepithelium single cells which had a membranous apical cytoplasm and engulfed intraepithelial lymphocytes were vimentin-immunoreactive. All other epithelial cells of the lymphoepithelium and of the surrounding airway epithelium did not bind vimentin antibodies. The results support the hypothesis that the membranous epithelial cells in the lymphoepithelium of rabbit BALT are analogous with intestinal M-cells, which in rabbit Peyer's patches and appendix are selectively labelled by vimentin antibodies. PMID- 1459868 TI - Physiologist views osteopathic medicine from different angle. PMID- 1459869 TI - Serologic testing only part of Lyme diagnosis. PMID- 1459870 TI - Rising US infant mortality rate requires action. PMID- 1459871 TI - Heed 'Voices From the Future' and reform GME training. PMID- 1459872 TI - Transplantation in the treatment of paralysis agitans (Parkinson's disease). AB - Over the past 3 years, there has been great interest in transplantation therapy in the treatment of Parkinson's disease. Following the impressive results reported by Madrazo in the spring of 1987, more than 350 cases of adrenal medullary implantation have been performed worldwide. There has been a significant reduction in "off" time and an increase in "on" time without chorea in 40% of patients having this procedure. The duration of effect is 1 year in half of these cases, with the other half (20% of all patients) still demonstrating significant improvement 3 years after the procedure. The mechanism of the bilateral beneficial improvement is unknown. The survival of adrenal medullary tissue has not been demonstrated at autopsy. It is thought that the mechanism of improvement involves either regenerative sprouting of the remaining dopamine producing neurons as a consequence of the release of neurotrophic factors or an interruption of the striatal pallidal output inhibitory influence of the basal ganglia on the thalamus (or both). Fetal mesencephalic implantation has also been attempted in more than 100 cases worldwide. The improvements when seen are not any more dramatic than those following the best results of adrenal medullary implantation. Graft survival has not been proved; it remains a possibility that interruption of the putamino-subthalamic pallidal pathway or a trophic influence of the tissue provides an alleviation in parkinsonism. The ethical controversy, need for long-term immunosuppression, and difficulty with obtaining tissue of the appropriate age and delivering the appropriate quantity to the putamen have made this technique less than adequate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459873 TI - Managing a patient with progressive HIV disease. AB - This monthly series was developed from the AOA Task Force on AIDS Writers' Workshop, held August 16 to 18, 1991, in New York. The workshop was sponsored by an education grant from Burroughs Wellcome. It will provide brief clinical updates and perspectives on the human immunodeficiency virus (HIV). Readers may request tear sheets from the AOA editorial offices. PMID- 1459874 TI - Voices From the Future: what students, interns, and residents want from osteopathic graduate medical training. AB - The need to attract students to--and keep them in--osteopathic internship and residency programs is great. Recognizing this fact, the osteopathic hospitals, through the American Osteopathic Hospital Association, have placed a renewed focus on liaisons with osteopathic medical education. Voices From the Future represents one such effort. This report reveals how osteopathic medical students, interns, and residents perceive the current state of osteopathic graduate medical education programs as well as the changes that they would like to see incorporated. PMID- 1459875 TI - Guillain-Barre syndrome, pregnancy, and plasmapheresis. AB - The case of Guillain-Barre syndrome (acute inflammatory polyradiculoneuritis) in pregnancy reported here brings the total reported number to 35. The patient had plasmapheresis with no maternal or fetal complications. She did not require mechanical ventilation. This is only the fifth reported case of Guillain-Barre syndrome in the gravid patient involving plasmapheresis. There have been no controlled studies assessing the safety of plasmapheresis in the pregnant patient with the disorder. The possible risks of the procedure need to be weighed against the high maternal mortality rate in such a patient. PMID- 1459876 TI - Relationship between CNV asymmetries and individual differences in cognitive performance, personality and gender. AB - This study used verbal and spatial variants of a cognitive 'match/mismatch' paradigm to explore relationships between functional brain asymmetries and individual differences in cognitive performance, personality and gender. Contingent negative variation (CNV) elicited in the 'match/mismatch' paradigm was recorded from central (Cz, C3 and C4) derivations in two male and one female samples. Results indicated gender differences in both the degree and direction of CNV asymmetries. Males showed a left hemisphere asymmetry in the verbal task and a right hemisphere asymmetry in the spatial task, with significant laterality (C3 C4) differences between tasks across the foreperiod. Females showed a left hemisphere asymmetry in both tasks with laterality differences between tasks confined to the early part of the foreperiod. CNV amplitude in the verbal task correlated with verbal memory performance and verbal I.Q. CNV amplitude in the spatial task correlated with visuospatial memory performance. Social extraversion was associated with greater left-hemisphere asymmetry in both tasks, while behavioural extraversion was associated with left-hemisphere asymmetry in the verbal task only, and with smaller verbal than spatial CNVs. PMID- 1459877 TI - Bilateral electrodermal activity: reliability, laterality and individual differences. AB - A first aim of the present study was to estimate the short- and long-term stability of individual response patterns in bilateral electrodermal activity (EDA). A second aim was to examine the relationship of individual brain laterality to both peak amplitude and peak time based electrodermal asymmetry. Additionally, subjects were presented with verbal and spatial tasks to estimate the balance of left/right asymmetry in cerebral activation at time of testing. Finally, the influence of smoking, coffee consumption and subjective circadian phase (morningness/eveningness, subjects' rise time) on bilateral asymmetry and EDA lability was examined. Results indicated moderate to high short-term reliabilities of EDA laterality coefficients, but insufficient long-term stability. Handedness and conjugate lateral eye movements (CLEMs) were not related to asymmetry of EDA, but a significant interaction between CLEM tendency and smoking/nonsmoking on laterality of both EDA parameters was observed. Amount of coffee consumption was also significantly related to electrodermal asymmetry. Analysis of performance data demonstrated that intraindividual shifts of EDA laterality from one recording session to a following one were associated with corresponding shifts in accuracy of verbal/spatial performance. Degree of subjects' electrodermal lability differentiated significantly between speed and accuracy of performance in both verbal and spatial tasks, and was substantially related to subjects' rise time. PMID- 1459878 TI - The effect of participation in an exercise training program on cardiovascular reactivity in sedentary middle-aged males. AB - Exaggerated cardiovascular reactivity to mental stressors may be a risk factor for cardiovascular disease. To determine if participation in a moderate intensity aerobic exercise training program reduces cardiovascular reactivity to laboratory stressors, 40 sedentary middle-aged males were randomly assigned: training group (n = 25) and control group (n = 15). Cardiovascular reactivity during and after three mental stressors (passive responding, push-button Stroop and verbal Stroop) and mild exercise (bicycle ergometer) was assessed before and after an 8-week intervention. VO2(peak) was determined using the Balke protocol. Among 19 subjects who completed the training, VO2(peak) increased 13.7%. Also, trained compared to untrained subjects showed significant reductions in baseline and absolute heart rate responses to all stressors. Baseline adjusted heart rates were significantly lower during push-button Stroop recovery and during verbal Stroop. Blood pressure, T-wave amplitude, finger pulse amplitude and pulse transit time responses were unaffected by exercise training. It was concluded that participation in a short-term, moderate intensity aerobic exercise training program may have a cardioprotective effect by significantly reducing absolute and baseline-adjusted heart rate responses to stressors. PMID- 1459879 TI - Basic emotions reflected in EEG-coherences. AB - The differentiation of basic emotions by means of EEG power spectra has been discussed extensively by Machleidt et al. (1989). The present contribution concentrates on the interhemispheric coupling of different EEG-signals as depending on the modulation of these emotions. In the first part the estimation and interpretation of squared coherence spectra is outlined. Results from this technique are presented in the following section. Intention, Aggression and Joy are mainly characterized by an increase of alpha-coherence, whereas a decrease is seen for Anxiety and Sorrow. These effects showed a widespread distribution. PMID- 1459880 TI - Distributions of the Nd and P300 in a normal sample. AB - To obtain objective criteria for assessing the attentional and cognitive functioning of psychiatric populations, we attempted to standardize values of two components in Event-Related Potentials (ERPs), namely the attention-related negative potential (Nd) and the P300, in normal populations. The study consisted of 100 healthy volunteers (50 females, 50 males) who were given the task of making dichotic syllable discriminations requiring key-press responses. Their ages ranged between 18 and 59 years (mean +/- S.D., 32.3 +/- 11.3 years). Nd was found to be maximum in the Fz region, P300 being maximum in the Pz region. The means and standard deviations of Nd and P300 areas in their maximum regions were 554.1 +/- 307.8 microV ms and 2148.5 +/- 1248.5 microV ms, respectively. The transformation plot for symmetry indicated the suitable power of transformation to be 1/2 for both Nd and P300 distributions. After being transformed into square root values, the distribution patterns of Nd and P300 areas were examined. When the lower limit of normal values was tentatively assigned to mean -2 S.D. using square-root transformed data for both Nd and P300, 97% of the subjects were found to display values above the lower normal limit for Nd, and 98% for the P300. Neither, Nd nor P300 areas correlated with age, while P300 latencies displayed a weak positive correlation with age. Females displayed relatively larger values than males for Nd and P300 areas and P300-peak amplitudes. However, the differences between females and males were not statistically significant. Females and males showed nearly equal P300-peak latencies. PMID- 1459881 TI - Evoked potential topography in major depression. I. Comparisons with nonpatients and schizophrenics. AB - This study compared evoked potential (EP) topography in major depression (MD), schizophrenia and nonpatient controls. EPs to four kinds of stimuli were recorded from 15 locations. Patients were 69 MDs and 52 schizophrenics, currently unmedicated. EP waveforms of 195 controls were subjected to principal component factor analysis (PCA). The structures of 32 factors so extracted have been shown to encompass the data space of disparate groups; they were used to compute factor scores for all subjects. Age- and gender-matched groups were compared. Factor scores were normalized across leads (Z-transform) to distinguish between topographic and mean level differences. Topographic differences (P < 0.05) between MD and controls were demonstrated for scores of 8 factors, with 2 others at P = 0.053. Unlike those for schizophrenia/control comparisons, these topographic differences did not converge regionally in MD. EP findings were not related to duration of withdrawal from drugs. There were few differences between bipolar and unipolar patients. Topographies of 5 factors differed between MDs and schizophrenics; these involved all modalities and reflected long latency, cognition-related events, such as P300. These topographic differences were antero posterior (AP); values were greater posteriorly in MDs and anteriorly in schizophrenics. Deviant AP gradients appear specific to MD; gradients were similar in schizophrenics and controls. PMID- 1459882 TI - Evoked potential topography in major depression. II. Comparisons between subgroups. AB - Brief Psychiatric Rating Scale (BPRS) ratings of 69 patients with major depression (MD) were employed in an attempt to define subgroups of MD with more homogeneous evoked potential (EP) findings than the MD group as a whole. Correlations were computed between 6 BPRS ratings and scores for 32 EP factors; 14 correlations were significant. These indicated mainly that EP values were related to severity of depression. When age- and gender-matched groups of MDs with above- and below-median depressive mood (D) ratings were compared with controls, 3 of the 10 factors differing significantly between groups gave evidence of two different subgroups of MD. EPs of these subgroups differed from those of controls in opposite directions. Such bidirectional differences from normal suggest differing pathophysiology in the subgroups and support the multiple process view of depression. PMID- 1459883 TI - Alertness pattern in healthy individuals of various ages. PMID- 1459884 TI - AERPs and clinical evolution of thought disorders over five years. AB - In a selective attention task, 21 Subjects detected rare randomized targets (P = 0.02) in a set of randomized standard tones. In one condition, Subjects focused their attention and detected targets in one ear, ignoring the other ear, and vice versa in the next condition. AERPs (auditory event-related potentials) were recorded at 5 electrode sites (10-20 system), at Fz, Cz, Pz, C3, C4, in two conditions varying speed of stimulation (randomized interstimulus intervals of 250-750 ms and 750-1500 ms). One group of 7 schizophrenics with the major syndrome of formal thought disorder (+FTD) was compared to 7 schizophrenics without the FTD syndrome (-FTD), and to 7 controls. The schizophrenic group was matched for age, education, sex, medication, hospitalization and intelligence score on abbreviated WAIS test. Ss were re-tested after 5 years following identical experimental and counterbalancing method to the pre-test. At re-test, similarly to pre-test, schizophrenics' AERPs showed smaller amplitudes, longer latencies, smaller attention effects than normals. -FTD schizophrenics showed intermediate values between the +FTD patients and normals. At retest, +FTD schizophrenics showed an aggravation of these AERP abnormalities while -FTD patients seemed to improve with larger amplitudes, faster latencies and better attention effects than at pre-test. Differential correlations between clinical and AERP indices indicated a dissociation between neurophysiological and clinical evolution: factors of dissociation included Andreasen's positive and negative indices of thought disorder, neuropsychological indices on the Luria-Nebraska scales, and severity of psychotic symptoms. PMID- 1459885 TI - Computerized EEG topography findings in schizophrenic patients before and after haloperidol treatment. AB - An increase of delta and fast beta activity in schizophrenic patients when compared with normal controls has been consistently reported. Topography of these abnormalities, in particular a possible frontal localization of delta, and their relationship to drug treatment and clinical status are still debated. In order to assess these issues, a multilead CEEG investigation was carried out in a group of 20 DSM-III-R schizophrenics, both before and after haloperidol treatment. All findings are described in terms of amplitude and relative power. Drug-free schizophrenics, when compared with a group of normal controls, showed a generalized increase of delta and fast beta, and a decrease of alpha 2 relative power. After acute treatment, patients showed a significant decrease of delta, and an increase of theta 2, beta 1, and beta 2. After 28 days of haloperidol treatment, similar changes were observed for delta, together with an increase of alpha 1, and a decrease of fast beta. PMID- 1459886 TI - An EEG computerized system for the evaluation of hypnotic drugs. AB - Digital recording of sleep EEG allows computer analysis and quantitative evaluations of sleep disorders and pharmacological effects. A system for polygraphic signal acquisition and storage, which performs a Fourier transform to compute series of spectra representing the evolution of EEG frequency composition through different sleep stages is described. The time course of spectral descriptors like relative band power is used to study the cyclic patterns of sleep and to compute the DSRI (Delta Sleep Regularity Index), a synthetic measure of sleep quality. The method is compared with conventional sleep scoring and examples of applications to normal, pathological and pharmacological conditions are shown. The topographical distribution of spectral parameters is analyzed by means of mapping techniques, allowing the detection of regional variations of EEG in specific pharmacological conditions. PMID- 1459887 TI - Modulation of somatosensory evoked potentials during isometric contraction in relation to hand use. AB - The aim of the study was to assess the effect of the hand used on the modulation of somatosensory evoked potentials (SEPs) during isometric contraction. SEPs to median nerve stimulation were assessed during dynamic (increase and decrease of force) and hold phases of isometric contractions. The experiments were carried out with the right or left hand. The changes in the SEP amplitude were found to vary with the hand used. When isometric contractions were performed by the right hand the amplitudes of the later components diminished during the dynamic phases, except for the component N140-P190 which increased. The amplitude of N55-P100 diminished during both the dynamic and hold phases. When isometric contractions were performed by the left hand the amplitudes of the early components diminished during the dynamic phases. These results show that the changes in SEP during isometric contraction depend on the hand used. PMID- 1459888 TI - Sewall Wright, 1889-1988: a brief biography. PMID- 1459890 TI - Relationship of milk production, milk expected progeny difference, and calf weaning weight in angus and simmental cow-calf pairs. AB - Milk EPD, used to predict the milk production potential of a parent's daughters, have been reported by all major cattle breed associations. Our objectives were to determine the relationship of milk EPD of a dam to actual milk production (both fluid and components) and offspring weaning weight. Angus (AN; n = 114) and Simmental (SM; n = 82) cows were machine-milked at approximately 60, 104, and 196 d postpartum after overnight calf removal. In addition, one herd of AN was also milked at approximately 35 and 145 d postpartum. A lactation curve was fitted to these measurements to estimate total milk production during lactation. Simple correlations between 205-d total milk yields (TMY) and adjusted 205-d calf weaning weight (WW) were .30 (P < .001) and .47 (P < .001) for AN and SM, respectively. Furthermore, milk EPD was positively correlated to adjusted WW (r = .38 P < .001; r = .39, P < .001) and TMY (r = .32, P < .001; r = .44, P < .001) for AN and SM cows, respectively. A 1-kg change in TMY changed WW by .014 +/- .006 kg (P < .001) in AN and by .032 +/- .009 kg (P < .001) in SM. A 1-kg change in milk EPD resulted in a 4.85 +/- 1.14 kg change in WW (P < .001) in AN and a 3.74 +/- 1.73 kg (P < .05) change in SM. Corresponding changes in TMY were 42.1 +/- 16.6 kg (P < .01) and 69.3 +/- 16.0 kg (P < .001) for AN and SM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459889 TI - Influence of fish meal and supplemental fat on performance of finishing steers exposed to moderate or high ambient temperatures. AB - Ninety-six Hereford x Angus steers (mean initial BW = 295 kg) were used in two growth experiments conducted at moderate and high ambient temperatures (AT), 48 steers per AT. Within each AT, calves were assigned to six dietary treatments consisting of a basal diet (approximately 60% corn and 20% grass hay) supplemented with either 0, 2.5, or 5% fat and with either soybean meal (SBM) or Menhaden fish meal (FM) included at levels such that a ratio of 16.3 kcal of NEm per kilogram of CP was maintained. Blood and ruminal fluid were collected 40 d before slaughter. During the final 28 d of the moderate AT experiment, apparent digestibility of dietary components was measured in four individually fed steers from each dietary treatment. Steer ADG was not affected by fat, and DMI and efficiency of gain were not affected (P > .10) by treatment. Average daily gain was lower for steers fed FM than for those fed SBM at moderate AT but higher at high AT (CP source x AT interaction; P < .05). Ruminal ratio of acetate to propionate declined linearly with increasing fat at moderate AT but was not affected by fat at high AT (fat x AT interaction trend; P = .08). Plasma urea N concentration increased linearly (P < .05) with increasing fat and was higher (P < .05) in steers kept at high than in those kept at moderate AT. Although apparent digestibility was not altered in steers fed FM, DM and NDF (P < .05) and ADF (P = .07) digestibility decreased with increasing fat in steers fed SBM (CP source x fat interaction).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459891 TI - Effect of frame size, muscle score, and external fatness on live and carcass value of beef cattle. AB - Commercial slaughter steers (n = 329) and heifers (n = 335) were selected to vary in slaughter frame size and muscle thickness score, as well as adjusted 12th rib fat thickness. After USDA carcass grade data collection, one side of each carcass was fabricated into boneless primals/subprimals and minor tissue components. Cuts were trimmed to 2.54, 1.27, and .64 cm of external fat, except for the bottom sirloin butt, tritip, and tenderloin, which were trimmed of all fat. Four variable regression equations were used to predict the percentage (chilled carcass weight basis) yield of boneless subprimals at different fat trim levels (.64, 1.27, and 2.54 cm) as influenced by sex class, frame size, muscle score, and adjusted 12th rib fat thickness. Carcass component values, total carcass value, carcass value per 45.36 kg of carcass weight, and live value per 45.36 kg of live weight were calculated for each phenotypic group and external fat trim level. Carcass fatness and muscle score had the most influence on live and carcass value (per 45.36 kg weight basis). Carcasses with .75 and 1.50 cm of fat at the 12th rib were more valuable as the trim level changed from 2.54 cm to .64 cm; however, for carcasses with 2.25 cm of fat at the 12th rib, value was highest at the 2.54 cm trim level. Value was maximized when leaner cattle were closely trimmed. There was no economic incentive for trimming light-muscled or excessively fat carcasses to .64 cm of external fat. PMID- 1459892 TI - The effectiveness of the best linear unbiased prediction of beef sires using field data collected from small farms. AB - Beef sire evaluation using BLUP was investigated under field conditions at small scale farms. The 6,848 records on fattened Japanese Black cattle steers were obtained from 1981 through 1987. The average number of steers in the subclass of market-year-farm was 5.2. A sire-maternal grandsire mixed model with relationships was used to analyze the data to yield BLUP for the sire and maternal grandsire effects. The regression coefficients of the realized value of progeny on the predicted value calculated using BLUP procedures for daily gain, carcass weight, and marbling score were 1.027, 1.054, and .917, respectively (i.e., the regression almost equaled 1). Therefore, BLUP was shown to be very effective in predicting offspring performance, even using field records collected from small-scale farms. PMID- 1459893 TI - Animal model for genetic evaluation of multibreed data. AB - Extension of beef cattle genetic evaluation procedures to multibreed data sets is proposed as a way to allow inclusion of crossbred animals into current analyses and to provide comparisons between purebred animals of different breeds. Previous papers dealing with multibreed BLUP have proposed sire or sire-maternal grandsire models. Because current models used in the beef industry are predominantly of the reduced animal model form, models were developed for animal model and reduced animal model mixed-model evaluations that would account for fixed and random additive genetic effects, along with fixed and random nonadditive genetic effects for populations with heterogeneous means and variances. PMID- 1459894 TI - Increased litter size in Rambouillet sheep: I. Estimation of genetic parameters. AB - The variance and covariance components needed to estimate heritabilities of and genetic correlations among litter size, ovulation rate, scrotal circumference, and BW in a flock of Rambouillet sheep were estimated using REML via an expectation-maximization type algorithm. The heritability estimates from univariate analyses were .14, .21, .25, .36, and .15 for litter size, ovulation rate, scrotal circumference, 180-d BW of females, and 180-d BW of males, respectively, and average heritability estimates from bivariate analyses were .19, .20, .20, .34, and .10 for litter size, ovulation rate, scrotal circumference, 180-d BW of females, and 180-d BW of males, respectively. The genetic correlation between litter size and ovulation rate was near unity. Body weight in ewes had a moderate genetic correlation with both litter size (.22) and ovulation rate (.20) and a low residual correlation with both litter size (.03) and ovulation rate (.09). The genetic correlation between BW in rams and scrotal circumference was 0, whereas the residual correlation was .71. The genetic correlations of scrotal circumference with litter size and ovulation rate were .25 and +.20, respectively. PMID- 1459895 TI - Increased litter size in Rambouillet sheep: II. Expected responses from alternative selection criteria. AB - The variance and covariance components estimated from an experimental flock of Rambouillet sheep were used to predict response in litter size to direct and indirect selection. Indirect traits considered were ovulation rate and scrotal circumference. Ovulation rate was the most useful indirect selection criterion for genetic improvement of litter size. Expected response in litter size to indirect selection on ovulation rate was 93% as large as the expected response to direct selection on litter size. Selection based on an index of litter size and ovulation rate was estimated to produce 123% as much response in litter size as selection on litter size alone, and selection on an index of litter size, ovulation rate, and scrotal circumference resulted in 133% as much response in litter size as direct selection on litter size. PMID- 1459896 TI - Performance of three tropical hair sheep breeds. AB - The performance of three hair sheep breeds (Brazilian Somali, Morada Nova, and Santa Ines) was evaluated in the production environment of northeastern Brazil. Data from a total of 524 lambs sired by 21 rams and out of 190 ewes were analyzed. These data were collected from 1980 to 1983 at Sobral, Brazil from an experiment designed to compare performance of the three breeds. The traits included weights of lambs at birth, weaning, 8 mo, 10 mo, and yearling ages and ewe characters of weight at lambing (EWT), total lamb weight born (LWB), total lamb weight weaned (LWW), and prolificacy rate (PR). Differences (P < .01) among breeds were found for all characters. The Brazilian Somali, the smallest and slowest-gaining breed, was less sensitive to yearly variation than were the other breeds. The Santa Ines, the largest and fastest-gaining breed, was superior in LWB and LWW per ewe lambing. Averaged over the 4-yr period, the Morada Nova had the highest PR (1.82), and the Brazilian Somali and Santa Ines had similar PR (1.39 and 1.31, respectively). Environmental effects on PR due to yearly rainfall quantity and distribution pattern influenced lamb growth up to weaning and ewe reproduction performance. Breed x year (P < .05) interaction effects on PR were largely attributable to the Somali breed's exhibiting higher PR than the Santa Ines and Morada Nova breeds during the relatively wet years of 1981 and 1982. PMID- 1459897 TI - Technical note: a noninvasive procedure for measuring goat heart rates. AB - Heart rates were obtained simultaneously from FM radio transmitters and heart rate monitors externally mounted on unanesthetized and unrestrained mixed-breed goats. Data from transmitters were highly correlated (r = .92, P < .0001) with data from monitors and the percentage difference in heart rates between the two devices was less than that observed between animals. Analyses also revealed that radio transmitters provided a reliable, repeatable, and valid method for the noninvasive measurement of goat heart rates. PMID- 1459898 TI - Measures of libido and their relation to serving capacity in the ram. AB - The purpose of this study was to determine whether the ejaculation rate (serving capacity) of sexually experienced rams could be estimated by selected measures of sexual libido when rams were exposed to estrous ewes under conditions that prevented copulations. Twenty-four crossbred rams selected for either high or low rates of copulation were exposed to two restrained estrous ewes under three treatment conditions that 1) permitted the full range of precopulatory and copulatory behaviors, 2) permitted precopulatory behaviors and mounting but precluded copulation, or 3) permitted precopulatory behaviors but not mounting or copulation. Frequencies of precopulatory behaviors (bouts of leg-kicking and anogenital sniffing) in each of the three treatment conditions and mounting frequency in Treatment 2 occurred in proportion to the ram's characteristic ejaculation rate (P < .001), suggesting that the mating potential of rams can be estimated under conditions that preclude copulation. Frequencies of precopulatory behaviors and mounting were lower when the rams were allowed to copulate, due largely to periods of sexual inactivity after ejaculations. PMID- 1459899 TI - Influence of trenbolone acetate combined with estradiol-17 beta on growth performance, body characteristics, and chemical composition of goat kids fed milk and slaughtered at different ages. AB - The effects of anabolic agents (5 mg of estradiol-17 beta + 30 mg of trenbolone acetate) on body characteristics and chemical composition of gain were studied in 58 intact male goat kids fed milk replacer. Four kids were slaughtered at 7 d of age to constitute the initial group. The other kids were allotted in a 2 x 3 factorial arrangement with slaughter age (41, 49, and 56 d of age) and treatment (control and implanted at 21 d old) as factors. Energy intake decreased during the first 4 wk after treatment; implanted kids had the same ADG as controls but a better energy efficiency (P < .05). During the last week of the trial, energy intake was the same; treated kids tended (P < .10) to have a higher empty body gain (EBG). Anabolic agents increased carcass (P < .10) and hide proportions (P < .01) in empty BW and in EBG for all groups (except for carcass at 56 d old). Anabolic agents reduced the contribution of adipose tissues (P < .05), empty digestive tract (P < .05), and other organs (P < .01) to EBG. At all slaughter ages, the chemical composition of carcass and hide wet tissues, all dissectible adipose tissues, and EBG were altered by treatment. In these tissues (except for mesenteric fat tissue), water content increased and lipid content decreased (P < .05), but these effects diminished with age. Expressed on a DM basis, the CP content of the treated carcasses was increased in all groups (P < .05). Implanting high doses of steroids altered nutrient partitioning, which reduced fat and increased water and protein in the body. PMID- 1459900 TI - Performance, plasma hormones, histochemical and biochemical muscle traits, and meat quality of pigs administered exogenous somatotropin between 30 or 60 kilograms and 100 kilograms body weight. AB - Forty-five Large White barrows were injected daily i.m. with either excipient from 30 to 100 kg BW (CTRL), excipient from 30 to 60 and porcine somatotropin (pST; 100 micrograms/kg BW) from 60 to 100 kg BW (pST-60), or pST (100 micrograms/kg BW) from 30 to 100 kg BW (pST-30). Somatotropin accelerated overall growth rate (+4 and +9% for pST-60 and pST-30, respectively), increased longissimus (+10.3 and +14.7%) and semitendinosus (+17 and +13%) muscle weights, and decreased backfat (-49 and -58%) and leaf fat (-49 and -53%) weights. The administration of pST resulted in a similar increase in muscle fiber size for all fiber types in both longissimus (LM) and semispinalis (SS) muscles (+21%). Somatotropin had otherwise little effect on muscle fiber types and biochemical traits of LM, whereas dramatic changes were observed in SS. The relative area occupied by Type IIB fibers was increased (+22 and +29%) and that of Type I fibers was decreased (-10 and -15%). In pST-30 animals, myosin ATPase activity (+15%) and native myosin fast isoform proportion (+10%) were augmented, and energy metabolism was more glycolytic (lactate dehydrogenase: +25%) and less oxidative (citrate synthase: -13%; beta-hydroxyacyl-CoA dehydrogenase: -21%). Compared to CTRL animals, administration of pST increased muscle water concentration (LM: +.8 and +1.1%: SS: +3.3 and +3.3%) and decreased intramuscular fat (LM: -29 and -27%; SS: -39 and -50%). The pH measured 45 min and 24 h postmortem, glycogen content, reflectance, and index of light diffusion were mostly not affected by pST treatment. In conclusion, pST had a very favorable effect on growth performance without any important effect on meat quality traits except for the reduction in intramuscular lipid content. The results indicated that the effects of pST on muscular histochemical and biochemical characteristics were different in LM and SS muscles. PMID- 1459901 TI - The effect of live weight gain and live weight loss on body composition of merino wethers: chemical composition of the dissected components. AB - Chemical composition of the dissected side parts and dissected side was measured during live weight gain (LWG) and live weight loss (LWL) to determine effects on the chemical composition of the dissected side parts. Thirty-five Merino wethers had ad libitum access to the experimental diet (17.23% CP and 12.09 MJ/kg of DE) to grow from 23.0 to 33.0 kg live weight and then were fed to lose a total of 10 kg in three periods of 25 d each at the rate of 133 g/d. Groups of five animals were slaughtered at live weights of 23.0, 26.3, 29.6, and 33.0 kg during LWG and 29.6 kg (first period), 26.3 kg (second period), and 23.0 kg (third period) during LWL. The greater dissected side weight in LWL animals than in LWG animals at 23.0 kg of live weight was due to the significantly greater chemical fat (P < .05) in the LWL animals than in the LWG animals at 23.0 kg. There were no significant differences between treatments in the protein and water weights in the dissected side. The general increase in the chemical fat in the dissected side of the LWL animals was due to the significant increase in the chemical fat in the muscle (P < .01) and bone (P < .01, 23.0 and 26.3 kg and P < .05, 29.6 kg) at each common slaughter weight and subcutaneous fat (P < .05), intermuscular fat (P < .05) kidney and channel fat (P < .05), and total side fat (P < .01) at 23.0 kg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459902 TI - Partial purification of somatotropin receptors from pig liver: they arise from a single somatotropin receptor messenger RNA transcript. AB - Specific binding sites for porcine somatotropin (pST) have been identified in pig liver microsomal membranes. Little information, however, is available about the size and number of ST receptor (ST-R) forms present. Therefore, the present study was conducted to characterize ST-R in pig liver using two approaches. In the first set of experiments, cross-linking of [125I]bST (bovine ST) to microsomal membranes, followed by gel electrophoresis under reducing conditions, revealed the presence of a predominant protein of 107 kDa and four other proteins of 71, 52, 40, and 26 kDa. In a second set of experiments, ST-R were partially purified using affinity chromatography. Binding studies indicated that there was an approximately 1,800-fold purification compared to liver homogenate. Two specific proteins of 107 and 40 kDa were detected after crosslinking of [125I]bST to partially purified ST-R. Northern blot analysis revealed that these proteins arise by posttranslational modification of a single 4.2-kilobase somatotropin receptor messenger RNA transcript. Although the present study indicates that several forms of ST-R are present in pig liver, it is not clear what physiological role these different ST-R play in mediating the hepatic effects of pST. It is evident, however, that the smaller proteins are generated from the 107 kDa protein, which is the predominant isoform present in liver microsomal membranes. PMID- 1459903 TI - Effects of the alpha 2-adrenoceptor agonist guanfacine on growth and thermogenesis in mice. AB - Guanfacine is an alpha 2-adrenoceptor agonist with antithermogenic properties. A single treatment of guanfacine caused a dose-related reduction in metabolic rate. The maximum reduction was 40%, and a dose of .5 mg/kg was close to that required to produce half this effect. It was determined whether the antithermogenic action of guanfacine would result in increased growth rate in mice. In animals treated once daily for 10 d (0, .125, .5, or 2 mg/kg), the drug caused dose-related reductions in feed intake, weight gain, and feed conversion efficiency. In a further experiment, mice were fed a restricted quantity of feed and treated for 14 d with guanfacine (.5 mg/kg twice daily). Because of repeated dosing, the antithermogenic effect of the drug was attenuated, so that metabolic rate was not lower in treated mice at the end of the experiment. Control and treated mice ate all the feed offered, but the guanfacine-treated group gained 2.9 g less weight (P < .01) than the controls. Half this difference in BW was accounted for by body water (P < .1), whereas body energy content was also reduced by the drug (P < .05). In a final experiment we sought possible sources of energy loss. Mice were treated with guanfacine (.5 mg/kg) three times over 24 h. Severe glucosuria was observed in the guanfacine-treated mice, with a tendency also toward increased output of fecal energy. We have confirmed that guanfacine has a powerful, if short-term, antithermogenic action. However, in mice, other effects of the drug on energy metabolism result in weight loss rather than growth stimulation. PMID- 1459904 TI - The effect of porcine somatotropin supplementation in pigs on the lipid profile of subcutaneous and intermuscular adipose tissue and longissimus muscle. AB - The effect of porcine somatotropin (pST) on the lipid profiles of adipose tissue and muscle was investigated. Sixteen crossbred barrows were injected daily with either 3 mg of pST or a placebo. After slaughter, total lipid and fatty acid composition of raw subcutaneous (SC) adipose and intermuscular (IM) adipose tissue and longissimus muscle were determined. The SC adipose tissue from pST treated pigs had a 7.5% decrease in total lipid content; specific fatty acids 16:0, 18:0, and 18:1(n-9)c decreased most. The IM fat from pST-treated pigs had lower levels of 16:0 and 20:0. There was no effect of pST treatment on the lipid profile of the longissimus muscle. The data suggest that pST treatment produces small but significant changes in the saturated fatty acid content of adipose tissue in pigs. PMID- 1459905 TI - Use of bioelectrical impedance to predict leanness of Boston butts. AB - The objective of this research was to make available bioelectrical impedance technology for the prediction of kilograms of lean and kilograms of fat-free muscle of Boston butts. Seventy butts were removed from 70 pork carcasses according to standard procedures (NAMP, #406), with the exception that the fat was not removed. After the weight in kilograms (BUTT) and internal temperature in degrees centigrade (TEMP) were recorded, each butt was measured for resistance (Rs, ohms), reactance (Xc, ohms), and distance (L, centimeters) between detector terminals four different ways: parallel or perpendicular to the top of the carcass and on either lean surface or fat surface of the cut. Each cut was physically separated into lean, fat, and bone. Chemical composition (moisture, protein, and fat) was determined on the lean portion. Variable selection analysis was used to develop equations for predicting kilograms of lean and kilograms of fat-free muscle of Boston butts. Results of measurements of the four sites were quite similar; however, measuring perpendicularly on the lean surface is recommended. The prediction equation for kilograms of lean from measurements thus taken is as follows: .461-.0304 x TEMP + .576 x BUTT - .0118 x Rs + .00845 x Xc + .0630 x L. The respective coefficients of these independent variables for predicting kilograms of fat-free muscle are .537, -.0415, .479, -.0139, .00804, and .0764. In an industry application of these coefficients, recording temperature would not be imperative because the temperature range would be sufficiently narrow to render temperature of little practical influence when separating butts according to leanness.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459906 TI - The effect of postmortem time of injection and freezing on the effectiveness of calcium chloride for improving beef tenderness. AB - Three experiments were conducted to determine the effect of freezing and time postmortem on the effectiveness of injecting CaCl2 to tenderize beef. In Exp. 1, longissimus muscle treatments included 1) control 0 h, 2) CaCl2-injected 0 h, 3) control 24 h, and 4) CaCl2-injected 24 h. Injection consisted of .3 M CaCl2 at 10% by weight. Injecting CaCl2 at 24 h postmortem reduced (P < .05) shear force requirements compared with the 24 h control but did not (P < .05) tenderize meat as much as injecting at 0 h. In Exp. 2, longissimus muscle treatments included the following: 1) aged 2 d; 2) aged 7 d; 3) frozen d 1, thawed, aged 6 d; 4) CaCl2-injected d 1, aged 6 d; 5) frozen d 1, thawed, CaCl2-injected, aged 6 d; and 6) CaCl2-injected d 1, frozen, thawed, aged 6 d. Injection alone at d 1 or freezing, then thawing and injecting resulted in the lowest (P < .05) shear force requirements. In Exp. 3, longissimus muscle treatments included the following: 1) aged 1 d; 2) aged 7 d; 3) CaCl2-injected 0 h, aged 7 d; 4) CaCl2-injected d 1, aged 6 d; 5) frozen d 1, thawed, aged 6 d; and 6) frozen, thawed, CaCl2-injected, aged 6 d. Both d-1 injection alone and freezing, thawing, then injecting resulted in meat with shear force requirements similar to those of 0-h injected meat. The effect of treatments on cooking loss was inconsistent. Treatments that reduced shear force also reduced (P < .05) calpain and calpastatin activity proportionately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459907 TI - Tracer studies of urea kinetics in growing pigs: I. The effect of intravenous infusion of urea on urea recycling and the site of urea secretion into the gastrointestinal tract. AB - Four gilts (average BW 80 kg) were used in the first experiment to study the effect of i.v. infusion of urea on urea kinetics by means of a radioisotope dilution technique. The pigs were fed twice daily 600 g of a cornstarch-based diet formulated to contain 16% CP by supplementation with isolated soy protein. Infusion of urea, compared with saline, increased (P < .05) plasma urea concentration, urea pool size, urea entry, urea excretion, and urea degradation rates; urea turnover rate and urea space were not affected (P > .05). Expressed as a percentage of the total entry rate, a lower (P < .05) percentage of urea was recycled in pigs infused with urea. The urea infused was almost completely excreted in urine, so there were no differences (P > .05) in N balance. In the second experiment, four gilts (average BW 40 kg), fitted with ileocecal reentrant cannulas, were used to determine whether the upper or the lower digestive tract represents the preferential site of urea secretion in pigs. Two pigs were fed twice daily 600 g of a cornstarch-based diet, formulated to contain 16% CP from soybean meal. The other two pigs were fed the same diet in which 15% cornstarch was replaced by beet pulp. After labeling the body urea pool of one pig on each treatment with [15N]urea, the reentrant cannulas were disconnected to prevent the flow of digesta from the small into the large intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459908 TI - Tracer studies of urea kinetics in growing pigs: II. The effect of starch infusion at the distal ileum on urea recycling and bacterial nitrogen excretion. AB - Six gilts, with an average BW of 70 kg, were fitted with a simple T-cannula at the distal ileum to study the effect of continuous starch infusion on urea kinetics by means of a radioisotope dilution technique. The pigs were fed twice daily 600 g of a cornstarch-based diet formulated to contain 16% CP by supplementation with isolated soy protein. Infusion of starch, compared with water, decreased (P < .05) plasma urea concentration, urea pool size, and entry, excretion, and degradation rates; urea turnover rate and urea space were not affected (P > .05). Expressed as a percentage of total entry rate, approximately 40% of urea was recycled into the digestive tract in both infusion treatments. The stimulation of microbial fermentation in the large intestine resulted in an increase (P < .05) in fecal N excretion, which was mainly due to an increased excretion of bacterial N. This increase could not be attributed to a greater secretion of urea into the large intestine and its subsequent utilization by the intestinal microflora. The increased bacterial N assimilation after starch infusion led to a reduction in ammonia absorption from the large intestine, which in turn was reflected by a reduced urinary N excretion. As a result, the overall N balance was not affected. In a second experiment, two barrows, with an average BW of 80 kg, were fed twice daily 1.4 kg of a cereal-based diet. The body urea pool of both pigs was labeled with a single injection of 1 g and 2 g of [15N]urea, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459909 TI - Effects of exogenous emulsifiers and fat sources on nutrient digestibility, serum lipids, and growth performance in weanling pigs. AB - Three experiments were conducted to determine whether emulsifiers improve utilization of fat from diets for early-weaned pigs. In Exp. 1, 96 weanling pigs (17 d old) were used in metabolism cages, with main effects of fat source (soybean oil, tallow, lard, and coconut oil) and emulsifier treatment (no emulsifier, lecithin, and lysolecithin as 10% of the added fat). Soybean oil and coconut oil were more digestible than tallow and lard (P < .001). Tallow was more digestible when lecithin and lysolecithin were added (P < .007), and pigs fed lecithin had lower serum triglycerides and cholesterol than pigs fed lysolecithin (P < .03). In Exp. 2, 270 weanling pigs (21 d old) were used in a growth assay. Treatments were 1) control diet; 2) Diet 1 with soybean oil; 3) Diet 1 with tallow; 4, 5, and 6) Diet 3 with lecithin replacing 5, 10, and 30% of the tallow, respectively; and 7, 8, and 9) Diet 3 with lysolecithin replacing 5, 10, and 30% of the tallow, respectively. At d 14 of the experiment, digestibility of tallow was improved more by lecithin than lysolecithin (P < .008). For the total experiment (d 0 to 35), the control pigs had poorer gain:feed ratio than did the pigs fed the fat sources (P < .002). In Exp. 3, 420 weanling pigs (21 d old) were used. Treatments were 1) control diet with soybean oil; 2) Diet 1 with tallow; and 3, 4, and 5) Diet 2 with 10% of the added fat as soybean oil, lecithin, or monoglyceride, respectively. Adding soybean oil, lecithin, and monoglyceride to tallow increased digestibility of total fat (P < .07). From d 0 to 14, pigs fed soybean oil gained weight faster than pigs fed the other treatments (P < .06), and pigs fed tallow without emulsifiers had the lowest ADG. Considering all experiments, addition of emulsifiers increased digestibility of nutrients but had minimal effect on growth performance. PMID- 1459910 TI - Effects of feeding diets containing endophyte-infected fescue seed on luteinizing hormone secretion in postpartum beef cows and in cyclic heifers and cows. AB - Two experiments were conducted to investigate the effect of feeding endophyte (Acremonium coenophialum)-infected fescue (Festuca arundinacea Shreb.) seed on LH secretion in postpartum beef cows and in cycling heifers and cows. In Exp. 1, spring-calving primiparous Angus cows (n = 16) were pair-fed for 75 d diets that contained endophyte-free or endophyte-infected (95%) fescue seed that contained 1.3 micrograms/g of ergovaline and 5.2 mg/g of saturated pyrrolizidines. Serial blood samples for basal and GnRH-stimulated serum LH analysis were obtained on d 7, 28, 42, and 56 of the study. The endophyte had no effect on LH secretion (basal, pulse frequency, and amplitude) or milk production. Average daily gain was decreased (P < .05) in cows that consumed infected fescue seed compared with controls (-.20 vs -.01 kg, respectively). Basal serum prolactin concentrations were reduced (P < .01) in treated compared with control cows (8.9 vs 25.4 ng/mL, respectively) on d 70. In Exp. 2, cycling Angus heifers (n = 8; age = 2 yr) and cows (n = 8; age = 4 yr) stratified by age were pair-fed for 40 d diets that contained the noninfected or the highly infected fescue seed. Estrus was synchronized by prostaglandin F2 alpha (d 18 and 28). Serial blood samples for serum LH analysis were obtained on d 28 (luteal phase) and d 30 (follicular phase). The endophyte did not affect LH (P > .28) or prolactin (P > .16) secretion, whereas ADG was decreased (P < .05) in treated compared with control animals (.32 vs .70 kg/d, respectively). PMID- 1459911 TI - Effect of heat-stress on bovine embryo development in vitro. AB - Chronic elevation of uterine temperature has long been known to increase embryo mortality in dairy cattle. Short-term elevation in temperature of mouse embryos to 43 degrees C (acute) has been shown to induce intracellular production of heat shock proteins. In this study, in vitro development of bovine embryos was assessed during short-term (60 h) coculture with oviduct epithelial cells at 38.6 degrees C (T1), 40 degrees C (T2), 38.6 degrees C after a prior pulse treatment (20 min) at 43 degrees C with 5% CO2 (T3), or 38.6 degrees C after a prior pulse treatment (20 min) at 43 degrees C with 100% CO2 (T4). During incubation, embryos cocultured at 40 degrees C had a greater (P < .05) mean embryo development score at 36 h than embryos cocultured at 38.6 degrees C. At 60 h of incubation, embryo development scores were greater (P < .05) for embryos cultured at 38.6 degrees C than for those cocultured at 40 degrees C. The number of embryos hatched at 60 h was similar after coculture at 38.6 degrees C (T1) or a prior pulse treatment with 5% CO2 and 43 degrees C (T3), but the embryo development score at 60 h was greater (P < .05) for the pulse-treated embryos. Embryos in T4 had greater (P < .05) embryo development scores than did T1 embryos from 36 through 60 h. Pulse treatment (T4) resulted in a greater (P < .05) number of hatched embryos at 60 h than T1, T2, and T3. These results indicate a detrimental effect of a chronic elevation in temperature that was evident shortly after embryo hatching.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459912 TI - Effects of feeding ponderosa pine needles during pregnancy: comparative studies with bison, cattle, goats, and sheep. AB - Four experiments were conducted to determine the effect of feeding dried pine needles (Pinus ponderosa; PN) on the abortion rate of ruminants. In Exp. 1, cattle were fed 5.4 kg of PN daily for 21 d starting at 116, 167, 215, or 254 d of pregnancy. The PN did not cause abortions when started at 116 d; thereafter, the percentage of cows that aborted increased linearly, and the interval to abortion decreased linearly (both P < .01); all cows fed PN beginning at 254 d aborted. In Exp. 2, cattle were fed .7, 1.4, or 2.7 kg of PN for 21 d or 2.7 kg for 1 or 3 d. Sheep and goats were fed .8 and .5 kg of PN, respectively, starting at 121 d of pregnancy. The PN induced some abortions in cattle when fed for 1 (11%) or 3 (30%) d, but the abortion rate was greater (P < .01) when the PN were fed for longer periods of time (80, 90, and 100% aborted in 19, 17, and 10 d for .7-, 1.4-, and 2.7-kg doses, respectively). No goats or sheep aborted in response to PN feeding. Pregnancy rates during the next breeding season for cows that aborted in response to the PN were slightly higher than rates for control cows (94 vs 87%). In Exp. 3, buffalo (Bison bison) and cattle were fed 2.25 kg of PN from the same collection. Abortions were induced in all buffalo and cattle that were fed PN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1459913 TI - Ovarian follicular characteristics, embryo recovery, and embryo viability in heifers fed high-fat diets and treated with follicle-stimulating hormone. AB - Postpubertal beef heifers (n = 55) were used to examine the effects of high-fat diets, independently of energy intake, on nonesterified fatty acid and lipoprotein metabolic patterns, ovarian follicular dynamics, and embryo recovery/viability after FSH superstimulation. High-lipid (HL) diets (5.4% added fat) increased (P < .01) serum concentrations of cholesterol, but not of nonesterified fatty acids, during the 35-d period before FSH treatment. Development of medium-sized (5 to 9.9 mm) follicles was enhanced (P < .05) during this period in heifers fed the HL diet. The HL diet increased total cholesterol (P < .05) and progesterone (P = .14) concentrations in follicular fluid obtained at ovariectomy (n = 10) 60 h after the onset of FSH treatment, but neither estradiol-17 beta nor androstenedione was affected. Granulosa cells recovered from FSH-induced, estrogen-active follicles in heifers fed the HL diet produced greater quantities of progesterone (P = .06) and less estradiol-17 beta (P < .05) in vitro than did granulosa cells from heifers fed the normal lipid diet. Dietary treatment did not influence FSH-stimulated recruitment of medium and large follicles, number of ovulations, embryo recovery, or embryo viability. Data suggest that increments in dietary fat intake can alter specific aspects of ovarian steroidogenic potential and can increase the population of medium-sized follicles theoretically available for maturation and harvest during the estrous cycle. However, conditions that limited the latter process in the current experiment are not understood and require further investigation. PMID- 1459914 TI - Combined effects of diet and cold exposure on insulin responsiveness to glucose and tissue responsiveness to insulin in sheep. AB - Hyperglycemic clamp and hyperinsulinemic euglycemic clamp techniques were used to investigate effects of diet and cold exposure on insulin responsiveness to glucose and tissue responsiveness and sensitivity to insulin in adult rams. The sheep were fed a high-concentrate diet (80% concentrate and 20% roughage) and a high-roughage diet (20% concentrate and 80% roughage), both 70% above the ME requirement for maintenance, and were exposed to a thermoneutral environment (20 degrees C) and a cold environment (0 degrees C) for 2 wk. The estimated ME intake was greater (P < .01) for the high-concentrate diet than for the high-roughage diet. In the hyperglycemic clamp experiment, the ratio of the plasma insulin increment to the glucose infusion rate (insulin responsiveness to glucose) was lower during cold exposure than in the thermoneutral environment in sheep fed the high-concentrate diet but was unchanged in sheep fed the high-roughage diet. In the hyperinsulinemic euglycemic clamp experiment, the glucose infusion rate (tissue responsiveness to insulin) was higher (P < .01) for the high-concentrate diet than for the high-roughage diet, and it was also higher (P < .01) during cold exposure than in the thermoneutral environment, indicating that tissue responsiveness to insulin was intensified in sheep fed the high-concentrate diet during cold exposure associated with the higher energy intake. These results suggest that both reduced insulin responsiveness and enhanced tissue responsiveness to insulin in sheep exposed to cold were dependent on the type of diet. PMID- 1459915 TI - Prolactin and luteinizing hormone secretion in the pregnant pig. AB - Four pregnant, primiparous, crossbred gilts and six gilts from the same population that had been ovariectomized (OVX) for approximately 3 wk were placed in individual pens in an enclosed building. Blood samples were collected every 30 min for 12 h from all gilts via an indwelling jugular vein cannula when the pregnant gilts were at d 30, 50, 70, 90, and 110 of gestation. Serum was quantified for LH and prolactin (PRL) by RIA. The OVX gilts served as controls to ensure that any variations in serum LH and PRL concentrations observed in the pregnant animals were not due to environmental factors unrelated to pregnancy. Within the pregnant gilts, mean serum LH concentrations, mean basal serum LH concentration, and mean serum LH peak height were similar on all days; however, number of LH peaks on d 30, 50, and 70 were greater (P < .05) than on d 90 and 110, and number of LH peaks on d 50 was greater (P < .05) than that on d 70. Within the pregnant gilts, mean serum PRL concentration, mean basal serum PRL concentration, and mean PRL peak height were greater (P < .001) on d 110 than on all other days; however, number of PRL peaks were similar among days. Parameters of LH and PRL secretion in the OVX and pregnant gilts varied independently. Results of this study indicated that 1) LH secretion does not vary appreciably throughout pregnancy and 2) PRL secretion does not vary significantly during the first 90 d of pregnancy, after which it increases markedly on or before 110 d. PMID- 1459916 TI - Influence of model and marker on digesta kinetic estimates for sheep. AB - Several models and markers are available for digesta kinetic studies. In this study, kinetic estimates derived from chromium-mordanted hay or pellets were compared to estimates derived from rare earth markers (Yb, Dy, or Er) applied individually to samples. Twelve yearling rams (52 kg) were given ad libitum access to either hay or a commercial pelleted diet in a crossover experiment. Digesta kinetic estimates were obtained both by nonlinear analysis with two age independent rates (G1G1) or with gamma time dependency in the fast compartment (G2G1 to G4G1) and by linear regression of natural log transformed fecal marker concentrations (LN method of estimate). Model did not influence total tract (P > .21) or ruminal mean retention times (P > .87). Partitioning of total retention time was similar (P > .21) for the LN, G3G1, and G4G1 models, but the G1G1 and G2G1 models did not adequately fit these data. Nonlinear models overestimated, and LN underestimated, fecal DM output by 9% (SEM = 4.7) for the hay diet. All the nonlinear models provided fecal DM output estimates that were within 5% of actual fecal DM output, but the LN model underestimated it by 18% (SEM = 3.3) for the pelleted diet. Ruminal outflow rate was slower (P < .01) and both ruminal and total mean retention time estimates were longer (P < .01) for Cr than for the rare earths. Despite the marker chosen, relative diet effects were similar. The three rare earth markers gave identical results for digesta kinetic estimates, indicating that they are useful for simultaneous study of more than one ingredient or particle, but direct comparison of rare earth and Cr-mordant passage rates is not advisable. PMID- 1459917 TI - Sulfate supplementation of alpine goats: effects on milk yield and composition, metabolites, nutrient digestibilities, and acid-base balance. AB - Effects of sulfate supplementation on milk yield and composition, ruminal and blood metabolites, acid-base status, and nutrient digestibilities were determined using 30 multiparous, lactating Alpine does. Goats were fed isonitrogenous diets containing .16 (basal), .26, or .36% S (DM basis) during a 13-wk lactation trial that coincided with wk 3 to 15 of lactation. During wk 16 to 17, four does from each treatment were placed in a metabolism crate to measure nutrient digestibility and balance. Feed intake, yield of 4% fat-corrected milk, and milk S content were not affected by added S, but the goats fed the .26% S diet had a trend of higher persistency of lactation (P < .20). During wk 10 and 15 of lactation, milk solids-not-fat percentage was higher (P < .10) for does fed the .26% S diet. Sulfur supplementation resulted in quadratic decreases in ruminal ammonia N (P < .05) in wk 15 and in plasma urea N in wk 10 and 15 (P < .05) but in linear increases (P < .05) in ruminal protein S concentrations throughout the experiment. Added S had little effect on blood acid-base status. Apparent digestibilities of DM, OM, ash, ADF, and GE were increased linearly (P < .10) by added S. The milk N:S ratio remained constant. Increasing S from .16 to .26% of diet DM was beneficial to lactating Alpine goats during early lactation. PMID- 1459918 TI - A net carbohydrate and protein system for evaluating cattle diets: I. Ruminal fermentation. AB - The Cornell Net Carbohydrate and Protein System (CNCPS) has a kinetic submodel that predicts ruminal fermentation. The ruminal microbial population is divided into bacteria that ferment structural carbohydrate (SC) and those that ferment nonstructural carbohydrate (NSC). Protozoa are accommodated by a decrease in the theoretical maximum growth yield (.50 vs .40 g of cells per gram of carbohydrate fermented), and the yields are adjusted for maintenance requirements (.05 vs .150 g of cell dry weight per gram of carbohydrate fermented per hour for SC and NSC bacteria, respectively). Bacterial yield is decreased when forage NDF is < 20% (2.5% for every 1% decrease in NDF). The SC bacteria utilize only ammonia as a N source, but the NSC bacteria can utilize either ammonia or peptides. The yield of NSC bacteria is enhanced by as much as 18.7% when proteins or peptides are available. The NSC bacteria produce less ammonia when the carbohydrate fermentation (growth) rate is rapid, but 34% of the ammonia production is insensitive to the rate of carbohydrate fermentation. Ammonia production rates are moderated by the rate of peptide and amino acid uptake (.07 g of peptide per gram of cells per hour), and peptides and amino acids can pass out of the rumen if the rate of proteolysis is faster than the rate of peptide utilization. The protein-sparing effect of ionophores is accommodated by decreasing the rate of peptide uptake by 34%. Validation with published data of microbial flow from the rumen gave a regression with a slope of .94 and an r2 of .88. PMID- 1459919 TI - A net carbohydrate and protein system for evaluating cattle diets: II. Carbohydrate and protein availability. AB - The Cornell Net Carbohydrate and Protein System (CNCPS) has a submodel that predicts rates of feedstuff degradation in the rumen, the passage of undegraded feed to the lower gut, and the amount of ME and protein that is available to the animal. In the CNCPS, structural carbohydrate (SC) and nonstructural carbohydrate (NSC) are estimated from sequential NDF analyses of the feed. Data from the literature are used to predict fractional rates of SC and NSC degradation. Crude protein is partitioned into five fractions. Fraction A is NPN, which is trichloroacetic (TCA) acid-soluble N. Unavailable or protein bound to cell wall (Fraction C) is derived from acid detergent insoluble nitrogen (ADIP), and slowly degraded true protein (Fraction B3) is neutral detergent insoluble nitrogen (NDIP) minus Fraction C. Rapidly degraded true protein (Fraction B1) is TCA precipitable protein from the buffer-soluble protein minus NPN. True protein with an intermediate degradation rate (Fraction B2) is the remaining N. Protein degradation rates are estimated by an in vitro procedure that uses Streptomyces griseus protease, and a curve-peeling technique is used to identify rates for each fraction. The amount of carbohydrate or N that is digested in the rumen is determined by the relative rates of degradation and passage. Ruminal passage rates are a function of DMI, particle size, bulk density, and the type of feed that is consumed (e.g., forage vs cereal grain). PMID- 1459920 TI - Kinetics of hydration and effect of liquid uptake on specific gravity of small hay and silage particles. AB - Kinetics of hydration of ground hay and silage particles (2-mm screen), determined by a pycnometric technique, was best described by a two- and one-pool exponential model, respectively. Fractional rates of hydration of the large pool, detected in hay particles only, and of the small pool present in both hay and silage particles averaged .135 and .021 min-1, respectively. When hydration was complete, liquid associated with particles averaged 1.16, 1.90, and .83 g/g of insoluble DM for bromegrass hay, alfalfa hay, and alfalfa silage, respectively. Functional specific gravity, which accounts for the effect of associated gas volume, averaged 1.54, 1.46, and 1.54, but unit specific gravity, calculated to include the effect of gases and liquid of hydration, averaged 1.22, 1.14, and 1.26 for bromegrass hay, alfalfa hay, and alfalfa silage, respectively. Preservation of forage as silage not only lowered gas volume, but also reduced water-holding capacity, both of which contribute to greater unit specific gravity and faster rate of escape from the rumen. In addition, estimates of unit specific gravity of approximately 1.2 indicate that even in the absence of associated gas, hydrated forage particles would tend to escape the rumen at a slower rate than that achieved by more dense particles. PMID- 1459921 TI - Ruminal biohydrogenation of linoleoyl methionine and calcium linoleate in sheep. AB - Four ruminally and duodenally cannulated Hampshire wethers were used in a 4 x 4 Latin square experiment to determine whether linoleoyl methionine and calcium linoleate would increase duodenal flow of unsaturated fatty acids (C18:2 + cis C18:1). All animals received the same basal diet plus a treatment enclosed in gelatin capsules that were placed directly in the rumen. Of the four experimental treatments, one was a control (empty capsules) and three were 5 g of fatty acid equivalent as either free linoleic acid, calcium linoleate, or linoleoyl methionine. Linoleoyl methionine had the lowest ruminal disappearance of C18:2 + cis C18:1. Ruminal loss of unsaturated fatty acids from each supplement exclusive of feed unsaturated fatty acids was 69.8, 92.9, and 94.6% for linoleoyl methionine, free linoleic acid, and calcium linoleate, respectively. Duodenal flow of methionine also was higher for linoleoyl methionine than for control, free linoleic acid, or calcium linoleate (2.5, 1.7, 2.0, and 2.5 g/d, respectively). Plasma linoleic acid was higher for linoleoyl methionine than for control or free linoleic acid but was not different from calcium linoleate (22.0, 17.8, 18.9, and 20.2% of total fatty acids, respectively). Plasma methionine levels were not different among treatments. Intestinal disappearance of unsaturated fatty acids did not differ among treatments. Linoleoyl methionine resisted ruminal biohydrogenation and was digested normally in the intestine. Calcium linoleate did not escape biohydrogenation by ruminal bacteria. PMID- 1459922 TI - Factors that affect ovarian follicular dynamics in cattle. AB - Studies of ovarian follicular dynamics in cattle may lead to methods for improving fertility, for synchronizing estrus with more precision, and for enhancing superovulatory responses. Within an estrous cycle, two or three large (> 10 mm) follicles develop during consecutive waves of follicular growth. The last wave provides the ovulatory follicle, whereas preceding wave(s) provide follicles that undergo atresia. The life span of large follicles seems to depend on the pulsatile secretion of LH; decreased frequency of LH pulses results in atresia of large follicles. Aromatase activity in the walls of the largest follicles is greatest during the first 8 d of the estrous cycle and decreases by d 12. Steroidogenesis of the largest and second-largest ovarian follicles differs on d 5, 8, and 12 of the estrous cycle. Follicular dynamics are altered by negative energy balance and lactation. The number of large follicles and concentration of estradiol during the preovulatory period differs between postpartum lactating and nonlactating cows. Dietary fats stimulate follicular growth when they are fed to increase energy balance. Administration of bovine somatotropin decreases energy balance and has a differential effect on ovarian follicular responses; growth of the largest follicle does not change, but growth of the second-largest follicle is stimulated by somatotropin. Studies of follicular dynamics in lactating cows demonstrate changes in ovarian function associated with energy balance that may be related to inefficient reproductive performance of cows producing high yields of milk. PMID- 1459923 TI - Pharmacokinetics in immature animals: a review. AB - Differences in drug pharmacokinetics between newborn and adult mammals are reviewed. The pharmacokinetic alterations during the maturation process are related to changes in the pattern of absorption, distribution, metabolism, and renal excretion. The most pronounced feature in neonates vs adults is the prolonged elimination half-life of drugs. The main factors causing delayed elimination are under-developed renal clearance and immature metabolism of drugs. Special attention has to be paid to central nervous system depressants and to drugs that are extensively metabolized because they will accumulate with repeated dosing of newborn animals. PMID- 1459924 TI - Factors that affect drug disposition in food-producing animals during maturation. AB - Drugs administered to neonatal food-producing animals (cattle, sheep, goats, swine) may exhibit significantly different pharmacokinetic/disposition characteristics than they do in adult animals of the same species. Undesirable consequences such as suboptimum therapeutic concentrations, toxic effects, and violative tissue residues may result if adult dosage regimens are employed in young animals. Using selected drugs as examples, this paper reviews factors that contribute to differences in drug disposition in newborn vs adult animals. Immaturity of mechanisms involved in drug absorption, especially from gastrointestinal and parenteral sites of administration, and of drug distribution to sites such as plasma proteins, adipose tissue, and fluid compartments are considered. The role of developmental changes in drug biotransformation in the liver and other tissues and the maturation of excretory mechanisms, primarily from the kidney, in the increased rate of drug clearance during maturation is described. Pharmacokinetic studies with specific drugs in the target species are an important approach to establishing rational drug use in immature food producing animals. PMID- 1459925 TI - Pathology of soft tissue sarcomas. An introduction. AB - Recent progress in molecular biology, cytogenetics, classification and grading of soft tissue sarcomas is briefly reviewed. It is emphasized that peer review of histopathology is highly desirable. Finally, equipped with modern imaging techniques, the radiologist can anticipate an increasing role in the aspiration cytology of deep seated soft tissue tumors. PMID- 1459926 TI - The multidisciplinary approach to treatment of soft tissue sarcomas. AB - Soft tissue sarcomas are rare tumors including many histological subtypes. They are pre-eminently tumors for which the multidisciplinary approach to treatment is of utmost importance. The two most frequently applied staging systems both require experienced assessment of radiology and pathology, and stage is a prominent prognostic factor for survival that guides the choice of treatment modalities. For primary treatment radical surgery is still the backbone. In many instances postoperative radiotherapy is a valuable and often necessary complementary treatment. The role of preoperative radiotherapy and/or chemotherapy needs to be defined although preliminary results are interesting. Chemotherapy as an adjunct to surgery should still be considered investigational. In metastatic disease "standard" chemotherapy has a definitive though moderate activity, but recent data on dose-intensified chemotherapy suggest that results may be further improved. PMID- 1459927 TI - Imaging in the follow-up of soft tissue tumors. AB - Local recurrences of aggressive soft tissue tumors are frequent and very difficult to detect clinically after surgery and radiation therapy. Ultrasound is limited because the skin is thick. On contrast-enhanced CT, both scars and recurrences increase their signal. MRI is the best technique, and the only one we presently use in the detection of recurrent tumors. We are reporting 511 follow up examinations in 182 patients after tumor removal. All patients had histologic confirmation or at least 6 months follow-up. There were 164 malignant tumors and 18 cases of aggressive fibromatosis. PMID- 1459928 TI - Ultrasound evaluation of soft tissue tumors. AB - Because of its availability, ultrasound should be the preferred initial modality for the evaluation of palpable superficial masses. Most ultrasound units are equipped with high frequency probes that allow superficial focalization. The differential diagnosis of soft tissue masses and the sonographic features of some benign and malignant soft tissue lesions are reviewed in this article. After an initial ultrasound evaluation confirming the presence of a tumor, the need for and the role of other imaging modalities can be determined. In selected cases ultrasound may obviate the need for further imaging. MRI and CT should be reserved for cases in which sonography fails to establish a specific diagnosis or to demonstrate the limits of the soft tissue mass. PMID- 1459929 TI - CT of soft tissue tumors. AB - We review the documented strengths and weaknesses of CT in the evaluation of soft tissue tumors and we describe what we believe to be an optimal CT technique. We also briefly outline the relation of CT to the other techniques in the diagnosis of soft tissue tumors and relate some particular CT findings to the major tumor types. PMID- 1459930 TI - Magnetic resonance imaging of soft tissue tumors. AB - The value of magnetic resonance imaging (MRI) in histological classification was studied in a series of 164 histologically proven soft tissue tumors (STT) and was rather limited. MRI was only valuable in characterization of lipomatous, vascular and fibrous tumors. There are two main reasons for this limitation i.e. STT belonging to the same histological group may have different composition or different proportions in tumor components resulting in different MRI signals. Secondly tumor components may change individually or proportionally during natural evolution or as a consequence of therapy. Because well known grading parameters such as cellularity, mitotic rate, matrix and presence of necrosis all influence MRI signal intensity, the value of MRI in predicting malignancy is potentially high. To assess this value we retrospectively studied the findings in the first 141 soft tissue tumors (84 benign, 57 malignant) and evaluated a wide variety of MRI features (size, margins, signal homogeneity, shape, signal intensity, neurovascular and bone involvement, degree and pattern of enhancement and evidence of necrosis after injection of Gd-DTPA). Statistical analysis was carried out to determine accuracy of parameters individually and in combination, for predicting malignancy. Highest sensitivity was obtained for "absence of low signal intensity on T2" (100%), "mean diameter > 33 mm" (90%) and "inhomogeneous signal on T1" (88%). Highest specificity was obtained for "evidence of necrosis" (98%), "bone or neurovascular involvement or metastases" (94%) and "mean diameter > 66 mm" (87%). Association of best sensitivity (81%) and specificity (81%) was seen for "absence of low signal intensity on T2", "signal inhomogeneity on T1" and "mean diameter of the lesion > 33 mm". In a prospective study of 23 consecutive patients we reevaluated sensitivity and specificity in predicting malignancy of all parameters. Excellent correlation with the results of the retrospective study was found. Although a quantitative approach to the staging potentials of MRI was not possible, well known staging parameters are evaluated to the best by this method (size, depth, compartmental versus extra-compartmental location, relationship to adjacent structures). PMID- 1459931 TI - Reactive mesenchymal proliferation. AB - One hundred and thirteen cases in the files of the Netherlands Committee on Bone Tumors were diagnosed as heterotopic soft tissue ossification. Myositis ossificans was diagnosed in 62, ossifying hematoma in 21, and pseudomalignant osseous tumor of soft tissues in 30 cases. Antecedent trauma was present in 37%, 46% and 7%, respectively. Myositis ossificans arose in the large muscle groups of the thighs and upper arms; when closely related to the shaft of a bone, periosteal reactions were more outspoken. Pseudomalignant osseous tumor of soft tissues was located in the hands, feet, and pelvis, some cases were not in muscle groups and some were almost periosteal. Ossifying hematoma was located in the upper and lower legs and usually in close relation to bone. The three entities belong to the same kind of reactive mesenchymal proliferative process. The radiologic and histologic patterns are reflections of whether the lesions are closely localized to bone shafts or in soft tissues, e.g. in muscles and therefore the term "reactive mesenchymal proliferation" is preferred to myositis ossificans, pseudomalignant osseous tumor of soft tissues and ossifying hematoma. Diagnostic problems are encountered in early phases when cellularity, mitotic activity, and infiltrative spread suggest malignancy. Recognition of these reactions in early phases is important to avoid mutilating surgery. PMID- 1459932 TI - Vascular soft tissue tumors: medical imaging. AB - Histologically, tumors of the vascular system are divided into three categories. Benign types can be localized (hemangioma) or involve large segments of the body (angiomatosis). Vascular tumors of intermediate malignancy are known as hemangioendotheliomas. Angiosarcoma is one of the rarest malignant soft tissue neoplasms. The authors present the morphological and SI features of 17 histologically proven vascular tumors (16 benign, 1 malignant) examined by MRI. The results are compared with the findings on other imaging techniques. On T1-WI, the tumors are slightly hyperintense to muscle with interspersed areas of low SI corresponding to fibrous septa, calcifications, or fastly flowing blood, and areas of SI equal to fat. On T2-WI, the lesions are more homogeneous and markedly hyperintense to fat. MRI is superior to all other imaging techniques for evaluation of extent and characterization of vascular soft tissue tumors. Angiography remains helpful in demonstrating feeding or draining vessels. PMID- 1459933 TI - Adipose tumors of soft tissues. AB - Thirteen patients with lipoma were examined at least with MRI, which revealed homogeneous and high signal lesions in both T1 and T2 WI sequences. On CT, these lesions were characterized by very negative density values. Sonography was useful to differentiate a lipoma from an old hematoma that share the same signal on MRI. Eighteen cases of biopsy proven liposarcomas were evaluated with at least two techniques. Tumor heterogeneity was the most important clue to malignancy. With CT, contrast injection was necessary because two cases out of eight appeared homogeneous on native examinations. Lobular pattern and large size are constant signs associated with liposarcoma. The correlation of imaging and histology classification was only successful with differentiated tumors. Angiography unspecifically reveals the malignancy of liposarcoma. MRI is better than CT to evaluate tumor expansion and to differentiate the mass from the surrounding tissue. PMID- 1459934 TI - Diagnostic imaging of muscular tumors. AB - Eight patients with muscular tumors--all malignant--were reviewed. Seven patients were examined by magnetic resonance imaging. Some of them also underwent conventional radiology and computed tomography. One patient was examined by computed tomography only. An overview and short description of the muscular tumors are given. The findings with the different imaging techniques are presented, followed by a discussion of the role of the imaging techniques. The final conclusion is that MRI is the modality of choice for detection, staging, and follow-up of muscular tumors, although the signal intensity features are not always specific. PMID- 1459935 TI - Medical imaging of soft tissue tumors (STT) PMID- 1459936 TI - Chromosome partitioning in Escherichia coli. PMID- 1459937 TI - HMt, a histone-related protein from Methanobacterium thermoautotrophicum delta H. AB - HMt, a histone-related protein, has been isolated and characterized from Methanobacterium thermoautotrophicum delta H. HMt preparations contain two polypeptides designated HMt1 and HMt2, encoded by the hmtA and hmtB genes, respectively, that have been cloned, sequenced, and expressed in Escherichia coli. HMt1 and HMt2 are predicted to contain 68 and 67 amino acid residues, respectively, and have calculated molecular masses of 7,275 and 7,141 Da, respectively. Aligning the amino acid sequences of HMt1 and HMt2 with the sequences of HMf1 and HMf2, the subunit polypeptides of HMf, a histone-related protein from the hyperthermophile Methanothermus fervidus, revealed that 40 amino acid residues (approximately 60%) are conserved in all four polypeptides. In pairwise comparisons, these four polypeptides are 66 to 84% identical. The sequences and locations of the TATA box promoter elements and ribosome binding sites are very similar upstream of the hmtA and hmtB genes in M. thermoautotrophicum and upstream of the hmfA and hmfB genes in M. fervidus. HMt binding compacted linear pUC19 DNA molecules in vitro and therefore increased their electrophoretic mobilities through agarose gels. At protein/DNA mass ratios of < 0.2:1, HMt binding caused an increase in the overall negative superhelicity of relaxed, circular DNA molecules, but at HMt/DNA mass ratios of > 0.2:1, positive supercoils were introduced into these molecules. HMt and HMf are indistinguishable in terms of their abilities to compact and constrain DNA molecules in positive toroidal supercoils in vitro. Histone-related proteins with these properties are therefore not limited to reverse gyrase-containing hyperthermophilic species. PMID- 1459938 TI - Structure and expression of a cyanobacterial ilvC gene encoding acetohydroxyacid isomeroreductase. AB - Acetohydroxyacid isomeroreductase (AHAIR) is the shared second enzyme in the biosynthetic pathways leading to isoleucine and valine. AHAIR is encoded by the ilvC gene in bacteria. A 1,544-bp fragment of genomic DNA containing the ilvC gene was cloned from the cyanobacterium Synechocystis sp. strain PCC 6803, and the complete nucleotide sequence was determined. The identity of the gene was established by comparison of the nucleotide and derived peptide sequences with those of other ilvC genes. The highest degree of sequence similarity was found with the ilvC gene from Rhizobium meliloti. The isolated Synechocystis ilvC gene complemented an Escherichia coli ilvC mutant lacking AHAIR activity. The expressed Synechocystis gene encodes a protein that has a molecular mass of 35.7 kDa and that has AHAIR activity in an in vitro assay. Polyclonal antibodies raised against purified Synechocystis AHAIR produced a single band on a Western blot (immunoblot) of a Synechocystis cell extract and detected the protein in an extract of an E. coli ilvC mutant strain that was transformed with a plasmid containing the Synechocystis ilvC gene. The antibody did not react with an extract of an E. coli ilvC mutant strain that was transformed with a control plasmid lacking the Synechocystis ilvC gene or with an extract of an E. coli IlvC+ control strain. PMID- 1459939 TI - Cloning, sequencing, and high expression of the proline iminopeptidase gene from Bacillus coagulans. AB - The gene coding for proline iminopeptidase in Bacillus coagulans was cloned and expressed in Escherichia coli. Nucleotide sequencing revealed an 861-bp open reading frame with an unusual TTG initiation codon, encoding a 287-amino-acid protein. The calculated molecular weight of the product was 32,415. The amino acid sequences of the amino-terminal region and those of some peptide fragments obtained by endoproteinase Asp-N digestion of the purified enzyme completely coincided with those deduced from the nucleotide sequence. The rare TTG initiation codon that normally codes for leucine was translated as a formal initiation codon; a methionine residue was found at the amino terminus of the enzyme. By using a vector bearing the strong tac promoter, an expression level as high as 200-fold that of the first clone was achieved. The replacement of the TTG initiation codon with ATG and a simultaneous reduction of the distance to the tac promoter resulted in a further increase of 2.5-fold. The expressed enzyme was easily purified to homogeneity by hydrophobic chromatography on a Toyopearl HW 65C column and crystallization, with a recovery of activity of 36%. The molecular weight was found to be 33,000 by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration on a Hi-Load 16/60 Superdex 200 fast protein liquid chromatography column. The expressed enzyme showed the same catalytic and physicochemical properties as those of the wild type, specifically cleaving the N terminal proline from small substrates. PMID- 1459941 TI - Molybdoenzyme biosynthesis in Escherichia coli: in vitro activation of purified nitrate reductase from a chlB mutant. AB - All molybdoenzyme activities are absent in chlB mutants because of their inability to synthesize molybdopterin guanine dinucleotide, which together with molybdate constitutes the molybdenum cofactor in Escherichia coli. The chlB mutants are able to synthesize molybdopterin. We have previously shown that the inactive nitrate reductase present in a chlB mutant can be activated in a process requiring protein FA and a heat-stable low-molecular-weight substance. We show here that purified nitrate reductase from the soluble fraction of a chlB mutant can be partially activated in a process that requires protein FA, GTP, and an additional protein termed factor X. It appears that the molybdopterin present in the nitrate reductase of a chlB mutant is converted to molybdopterin guanine dinucleotide during activation. The activation is absolutely dependent upon both protein FA and factor X. Factor X activity is present in chlA, chlB, chlE, and chlG mutants. PMID- 1459940 TI - Genetic analysis of the tetA(C) gene on plasmid pBR322. AB - The TetA(C) protein, encoded by the tetA(C) gene of plasmid pBR322, is a member of a family of membrane-bound proteins that mediate energy-dependent efflux of tetracycline from the bacterial cell. The tetA(C) gene was mutagenized with hydroxylamine, and missense mutations causing the loss of tetracycline resistance were identified at 30 distinct codons. Mutations that encoded substitutions within putative membrane-spanning alpha-helical regions were scattered throughout the gene. In contrast, mutations outside the alpha-helical regions were clustered in two cytoplasmic loops, between helices 2 and 3 and helices 10 and 11, suggesting that these regions play a critical role in the recognition of tetracycline and/or energy transduction. All of the missense mutations encoded a protein that retained the ability to rescue an Escherichia coli strain defective in potassium uptake, suggesting that the loss of tetracycline resistance was not due to an unstable TetA(C) protein or to the failure of the protein to be inserted in the membrane. We postulate that the mutations encode residues that are critical for the active efflux of tetracycline, except for mutations that result in the introduction of charged residues within hydrophobic regions of the TetA(C) protein. PMID- 1459942 TI - Mechanism of action of cyclic beta-1,2-glucan synthetase from Agrobacterium tumefaciens: competition between cyclization and elongation reactions. AB - We have examined some aspects of the mechanism of cyclic beta-1,2-glucan synthetase from Agrobacterium tumefaciens (235-kDa protein, gene product of the chvB region). The enzyme produces cyclic beta-1,2-glucans containing 17 to 23 glucose residues from UDP-glucose. In the presence of added cyclic beta-1,2 glucans (> 0.5 mg/ml) (containing 17 to 23 glucose residues), the enzyme instead synthesizes larger cyclic beta-1,2-glucans containing 24 to 30 glucose residues. This is achieved by de novo synthesis and not by disproportion reactions with the added product. This is interpreted as inhibition of the specific cyclization reaction for the synthesis of cyclic beta-1,2-glucans containing 17 to 23 glucose residues but with no concomitant effect on the elongation (polymerization) reaction. Temperature and detergents both affect the distribution of sizes of cyclic beta-1,2-glucans, but glucans containing 24 to 30 glucose residues are not produced. We suggest that the size distribution of cyclic beta-1,2-glucan products depends on competing elongation and cyclization reactions. PMID- 1459943 TI - A new nylon oligomer degradation gene (nylC) on plasmid pOAD2 from a Flavobacterium sp. AB - Flavobacterium sp. strain KI725 harbors plasmid pOAD21, a derivative of nylon oligomer-degradative plasmid pOAD2, in which all of nylA (the gene for 6 aminohexanoate cyclic dimer hydrolase [EI]) was deleted but nylB (the gene for 6 aminohexanoate dimer hydrolase [EII]) was retained. KI725 showed no growth on unfractionated nylon oligomers (Nom1) obtained from a nylon factory as a sole carbon and nitrogen source (Nom1 minimum plate). Extracts of KI725 cells possessed hydrolytic activity for Nom1 (approximately 5% of the activity of KI72), but pOAD2-cured strains (KI722 and KI723) showed no activity. KI725R strains which grew on the Nom1 minimum plate were spontaneously isolated from KI725 at a frequency of 10(-7) per cell. Activity toward Nom1 was enhanced in KI725R strains (10 to 30% of the activity of KI72). This new Nom1 degrading enzyme (EIII, the nylC gene product) hydrolyzed not only Nom1 but also the N carbobenzoxy-6-aminohexanoate trimer, a substrate which was not hydrolyzed by either EI or EII. Cloning and sequence analysis showed that the nylC gene is located close to nylB on pOAD21 and is a 1,065-bp open reading frame corresponding to 355 amino acid residues. The nucleotide sequence of the nylC gene and the deduced amino acid sequence of EIII had no detectable homology with the sequences of nylA (EI) and nylB (EII). PMID- 1459944 TI - Stabilization of phosphorylated Bacillus subtilis DegU by DegR. AB - The production of Bacillus subtilis extracellular proteases is under positive and negative regulation. The functional role of degR, one of the positive regulators, was studied in relation to the degS and degU gene products, which belong to the bacterial two-component regulatory system. Studies with a translational fusion between the Escherichia coli lacZ and the Bacillus subtilis subtilisin (aprE) genes indicated that the stimulatory site of DegR lay upstream of position -140, with the region upstream of position -200 being the major target. It was also found that degS and degU were epistatic to degR. These results suggested some relationship among the degR, degS, and degU gene products. The DegR protein was purified to homogeneity, and its in vitro effect on the phosphorylation reaction involving DegS and DegU was studied. For this purpose, a soluble-extract system in which the formation and dephosphorylation of DegU-phosphate could be examined was devised. The addition of DegR to the soluble-extract system enhanced the formation of DegU-phosphate. The enhancing effect was found to be due to the protection of DegU-phosphate from dephosphorylation. From these results, it was concluded that the positive effect of DegR on the production of the extracellular proteases is brought about by the stabilization of DegU-phosphate, which in turn may result in the stimulation of transcription of the exoprotease genes. PMID- 1459945 TI - Participation of a cyanobacterial S layer in fine-grain mineral formation. AB - Cyanobacteria belonging to the Synechococcus group are ubiquitous inhabitants of diverse marine and freshwater environments. Through interactions with the soluble constituents of their aqueous habitats, they inevitably affect the chemistry of the waters they inhabit. Synechococcus strain GL24 was isolated from Fayetteville Green Lake, New York, where it has a demonstrated role in the formation of calcitic minerals. In order to understand the detailed interactions which lead to mineral formation by this organism, we have undertaken detailed ultrastructural studies of its cell surface and the initial events in mineral growth using a variety of electron microscopic and computer image enhancement techniques. Synechococcus strain GL24 has a hexagonally symmetrical S layer as its outermost cell surface component. The constituent protein(s) of this structure appears as a double band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with M(r)s of 104,000 and 109,000. We demonstrate that the S layer acts as a template for fine-grain gypsum and calcite formation by providing discrete, regularly arranged nucleation sites for the critical initial events in the mineralization process. To our knowledge, this is the first time that a bacterial S layer has been shown to have a role in mineral formation in a natural environment, and this report provides conclusive evidence for the specific involvement of bacterial surfaces in natural mineral formation processes. PMID- 1459946 TI - Interactions of Escherichia coli membrane lipoproteins with the murein sacculus. AB - Bifunctional cross-linking reagents were used to identify cell envelope proteins that interacted with the murein sacculus. This revealed that a number of [3H]leucine-labeled proteins and [3H]palmitate-labeled lipoproteins were reproducibly cross-linked to the sacculus in plasmolyzed cells. The results suggested that most of the cell envelope lipoproteins, and not only the murein lipoprotein, mediate interactions between the murein sacculus and the inner and/or outer membrane of the cell. PMID- 1459947 TI - Purification and characterization of the hydantoin racemase of Pseudomonas sp. strain NS671 expressed in Escherichia coli. AB - The hydantoin racemase gene of Pseudomonas sp. strain NS671 had been cloned and expressed in Escherichia coli. Hydantoin racemase was purified from the cell extract of the E. coli strain by phenyl-Sepharose, DEAE-Sephacel, and Sephadex G 200 chromatographies. The purified enzyme had an apparent molecular mass of 32 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. By gel filtration, a molecular mass of about 190 kDa was found, suggesting that the native enzyme is a hexamer. The optimal conditions for hydantoin racemase activity were pH 9.5 and a temperature of 45 degrees C. The enzyme activity was slightly stimulated by the addition of not only Mn2+ or Co2+ but also metal chelating agents, indicating that the enzyme is not a metalloenzyme. On the other hand, Cu2+ and Zn2+ strongly inhibited the enzyme activity. Kinetic studies showed substrate inhibition, and the Vmax values for D- and L-5-(2 methylthioethyl)hydantoin were 35.2 and 79.0 mumol/min/mg of protein, respectively. The purified enzyme did not racemize 5-isopropylhydantoin, whereas the cells of E. coli expressing the enzyme are capable of racemizing it. After incubation of the purified enzyme with 5-isopropylhydantoin, the enzyme no longer showed 5-(2-methylthioethyl)hydantoin-racemizing activity. However, in the presence of 5-(2-methylthioethyl)hydantoin, the purified enzyme racemized 5 isopropylhydantoin completely, suggesting that 5-(2-methylthioethyl)hydantoin protects the enzyme from inactivation by 5-isopropylhydratoin. Thus, we examined the protective effect of various compounds and found that divalent-sulfur containing compounds (R-S-R' and R-SH) have this protective effect. PMID- 1459948 TI - Cellobiose chemotaxis by the cellulolytic bacterium Cellulomonas gelida. AB - In the course of a study on the bacterial degradation of plant cell wall polysaccharides, we observed that growing cells of motile cellulolytic bacteria accumulated, without attachment, near cellulose fibers present in the cultures. Because it seemed likely that the accumulation was due to chemotactic behavior, we investigated the chemotactic responses of one of the above-mentioned bacteria (Cellulomonas gelida ATCC 488). We studied primarily the responses toward cellobiose, which is the major product of cellulose hydrolysis by microorganisms, and toward hemicellulose hydrolysis products. We found that cellobiose, cellotriose, D-glucose, xylobiose, and D-xylose, as well as other sugars that are hemicellulose components, served as chemoattractants for C. gelida, as determined by a modification of Adler's capillary assay. Competition and inducibility experiments indicated that C. gelida possesses at least two types of separately regulated cellobiose chemoreceptors (Cb1 and cellobiose, cellotriose, xylobiose, and D-glucose, and it is constitutively synthesized. The presence in C. gelida of a constitutive response toward cellobiose and of at least two distinct cellobiose chemoreceptors has implications for the survival of this cellulolytic bacterium in nature. A possible mechanism for cellobiose-mediated bacterial chemotaxis toward cellulose is proposed. We suggest that, in natural environments, motile cellulolytic bacteria migrate toward plant materials that contain cellulose and hemicellulose by swimming up cellobiose concentration gradients and/or concentration gradients of other sugars (e.g., xylobiose, D-xylose, and D glucose) formed by enzymatic hydrolysis of plant cell wall polysaccharides. PMID- 1459949 TI - Purification and characterization of a tetrachloro-p-hydroquinone reductive dehalogenase from a Flavobacterium sp. AB - Tetrachloro-p-hydroquinone (TeCH) is the first intermediate in pentachlorophenol (PCP) degradation by Flavobacterium sp. strain ATCC 39723. We previously purified a PCP hydroxylase that oxidized PCP to TeCH. Subsequently, we identified the reductive dehalogenation of TeCH to 2,3,6-trichloro-p-hydroquinone and then to 2,6-dichloro-p-hydroquinone in a cell extract with the reduced form of glutathione as the reducing agent under anaerobic conditions. Here we report the purification of a TeCH reductive dehalogenase that reductively dehalogenated TeCH to trichlorohydroquinone and then to dichlorohydroquinone. The enzyme was purified by protamine sulfate treatment, ammonium sulfate fractionation, and phenyl-agarose, anion-exchange, and gel filtration column chromatographies. As determined by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses, the protein has a molecular weight of about 30,000; nondenaturing polyacrylamide gel electrophoresis analysis suggests that the native enzyme exists as a dimer. The enzyme used glutathione but not NADPH, NADH, dithiothreitol, or ascorbic acid as the reducing agent. The optimal pH was close to neutral. PMID- 1459950 TI - Evidence for an S-layer protein pool in the peptidoglycan of Bacillus stearothermophilus. AB - Intact cells of Bacillus stearothermophilus PV72 revealed, after conventional thin-sectioning procedures, the typical cell wall profile of S-layer-carrying gram-positive eubacteria consisting of a ca. 10-nm-thick peptidoglycan-containing layer and a ca. 10-nm-thick S layer. Cell wall preparations obtained by breaking the cells and removing the cytoplasmic membrane by treatment with Triton X-100 revealed a triple-layer structure, with an additional S layer on the inner surface of the peptidoglycan. This profile is characteristic for cell wall preparations of many S-layer-carrying gram-positive eubacteria. Among several variants of strain PV72 obtained upon single colony isolation, we investigated the variant PV72 86-I, which does not exhibit an inner S layer on isolated cell walls but instead possesses a profile identical to that observed for intact cells. In the course of a controlled mild autolysis of isolated cell walls, S layer subunits were released from the peptidoglycan of the variant and assembled into an additional S layer on the inner surface of the walls, leading to a three layer cell wall profile as observed for cell wall preparations of the parent strain. In comparison to conventionally processed bacteria, freeze-substituted cells of strain PV72 and the variant strain revealed in thin sections a ca. 18-nm wide electron-dense peptidoglycan-containing layer closely associated with the S layer. The demonstration of a pool of S-layer subunits in such a thin peptidoglycan layer in an amount at least sufficient for generating one coherent lattice on the cell surface indicated that the subunits must have occupied much of the free space in the wall fabric of both the parent strain and the variant. It can even be speculated that the rate of synthesis and translation of the S layer protein is influenced by the packing density of the S-layer subunits in the periplasm of the cell wall delineated by the outer S layer and the cytoplasmic membrane. Our data indicate that the matrix of the rigid wall layer inhibits the assembly of the S-layer subunits which are in transit to the outside. PMID- 1459951 TI - Identification, cloning, and characterization of rcsF, a new regulator gene for exopolysaccharide synthesis that suppresses the division mutation ftsZ84 in Escherichia coli K-12. AB - A new gene, designated rcsF, was located adjacent to drpA at the 5.2-min position of the genetic map of Escherichia coli. The deduced amino acid sequence encoded by the rcsF gene indicates a small protein of 133 amino acid residues with a calculated pI of 10.8 that is rich in proline, serine, alanine, and cysteine residues. When overexpressed as a result of its presence on a multicopy plasmid, rcsF confers a mucoid phenotype and restores colony formation to ftsZ84 mutant cells on L agar medium containing no added NaCl. These two phenotypes are not observed in rcsB mutant cells. Ion mutant cells harboring an rcsF mutation accumulate considerably lower levels of exopolysaccharides, whereas the presence of a multicopy rcsF plasmid not only increases capsule synthesis but also confers a mucoid phenotype at 37 degrees C, a temperature at which ion mutant cells are known not to form mucoid colonies. RcsF does not stimulate the expression of rcsB, indicating that it exerts its action through the RcsB protein, possibly by phosphorylation. It is also shown that RcsF stimulation of capsule synthesis is RcsA-dependent, whereas colony formation of ftsZ84 mutant cells can be restored by RcsF in the absence of RcsA. PMID- 1459952 TI - Cloning and characterization of the Brucella ovis heat shock protein DnaK functionally expressed in Escherichia coli. AB - The Brucella ovis dnaK gene, homolog to the eukaryotic hsp70 genes, was cloned by using a Drosophila melanogaster probe. Comparison of B. ovis and Escherichia coli sequences revealed a similar organization for the dnaK and dnaJ genes and putative regulatory signals. In E. coli transfected with the cloned fragment, B. ovis hsp70 was expressed at 30 and 50 degrees C apparently under the control of its own promoter. The recombinant protein and a B. ovis native protein displaying the same molecular weight were both recognized by anti-E. coli DnaK serum. Native B. ovis protein was also recognized by sera of sheep either infected or vaccinated with an attenuated Brucella strain, suggesting that Brucella hsp70 could be up-regulated during host colonization. A thermosensitive E. coli dnaK mutant transfected with the cloned fragment recovered colony-forming ability at 42 degrees C, showing that the B. ovis DnaK protein could behave as a functional heat shock protein in E. coli. PMID- 1459953 TI - Dramatic changes in Fis levels upon nutrient upshift in Escherichia coli. AB - Fis is a small basic DNA-binding protein from Escherichia coli that was identified because of its role in site-specific DNA recombination reactions. Recent evidence indicates that Fis also participates in essential cell processes such as rRNA and tRNA transcription and chromosomal DNA replication. In this report, we show that Fis levels vary dramatically during the course of cell growth and in response to changing environmental conditions. When stationary phase cells are subcultured into a rich medium, Fis levels increase from less than 100 to over 50,000 copies per cell prior to the first cell division. As cells enter exponential growth, nascent synthesis is largely shut off, and intracellular Fis levels decrease as a function of cell division. Fis synthesis also transiently increases when exponentially growing cells are shifted to a richer medium. The magnitude of the peak of Fis synthesis appears to reflect the extent of the nutritional upshift. fis mRNA levels closely resemble the protein expression pattern, suggesting that regulation occurs largely at the transcriptional level. Two RNA polymerase-binding sites and at least six high affinity Fis-binding sites are present in the fis promoter region. We show that expression of the fis operon is negatively regulated by Fis in vivo and that purified Fis can prevent stable complex formation by RNA polymerase at the fis promoter in vitro. However, autoregulation only partially accounts for the expression pattern of Fis. We suggest that the fluctuations in Fis levels may serve as an early signal of a nutritional upshift and may be important in the physiological roles Fis plays in the cell. PMID- 1459954 TI - Role of PhoU in phosphate transport and alkaline phosphatase regulation. AB - The negative regulatory function of PhoU in alkaline phosphatase (AP) was suggested by the behavior of K10 phoU35 carrying a missense mutation whose product was detected by immunoblotting. To define more clearly the regulatory function of this protein for the synthesis of AP, we constructed a null mutation. The constitutive synthesis of AP in this phoU deletion strain confirmed the negative role of PhoU. However, the expression of the PhoU protein from an isopropyl-beta-D-thiogalactopyranoside-inducible promoter had no effect on the repression of AP synthesis. Furthermore, the involvement of PhoU in free-Pi uptake was demonstrated. These results provide evidence that PhoU participates in Pi transport and in the regulatory role of the phosphate-specific transport system. PMID- 1459955 TI - Functional and structural analyses of threonine dehydratase from Corynebacterium glutamicum. AB - Threonine dehydratase activity is an important element in the flux control of isoleucine biosynthesis. The enzyme of Corynebacterium glutamicum demonstrates a marked sigmoidal dependence of initial velocity on the threonine concentration, a dependence that is consistent with substrate-promoted conversion of the enzyme from a low-activity to a high-activity conformation. In the presence of the negative allosteric effector isoleucine, the K0.5 increased from 21 to 78 mM and the cooperativity, as expressed by the Hill coefficient increased from 2.4 to 3.7. Valine promoted opposite effects: the K0.5 was reduced to 12 mM, and the enzyme exhibited almost no cooperativity. Sequence determination of the C. glutamicum gene for this enzyme revealed an open reading frame coding for a polypeptide of 436 amino acids. From this information and the molecular weight determination of the native enzyme, it follows that the dehydratase is a tetramer with a total mass of 186,396 daltons. Comparison of the deduced polypeptide sequence with the sequences of known threonine dehydratases revealed surprising differences from the C. glutamicum enzyme in the carboxy-terminal portion. This portion is greatly reduced in size, and a large gap of 95 amino acids must be introduced to achieve homology. Therefore, the C. glutamicum enzyme must be considered a small variant of threonine dehydratase that is typically controlled by isoleucine and valine but has an altered structure reflecting a topological difference in the portion of the protein most likely to be important for allosteric regulation. PMID- 1459956 TI - Lysis of lysis-inhibited bacteriophage T4-infected cells. AB - T4 bacteriophage (phage)-infected cells show a marked increase in latent-period length, called lysis inhibition, upon adsorption of additional T4 phages (secondary adsorption). Lysis inhibition is a complex phenotype requiring the activity of at least six T4 genes. Two basic mysteries surround our understanding of the expression of lysis inhibition: (i) the mechanism of initiation (i.e., how secondary adsorption leads to the expression of lysis inhibition) and (ii) the mechanism of lysis (i.e., how this signal not to lyse is reversed). This study first covers the basic biology of the expression of lysis inhibition and lysis of T4-infected cells at high culture densities. Then evidence is presented which implies that, as with the initiation of lysis inhibition, sudden, lysis associated clearing of these cultures is likely caused by T4 secondary adsorption. For example, such clearing is often observed for lysis-inhibited T4 infected cells grown in batch culture during T4 stock preparation. The significance of this secondary adsorption-induced lysis to wild T4 populations is discussed. The study concludes with a logical argument suggesting that the lytic nature of the T4 phage particle evolved as a novel mechanism of phage-induced lysis. PMID- 1459957 TI - Cloning and characterization of the Bacillus subtilis hemEHY gene cluster, which encodes protoheme IX biosynthetic enzymes. AB - Mutations that cause a block in a late step of the protoheme IX biosynthetic pathway, i.e., in a step after uroporphyrinogen III, map at 94 degrees on the Bacillus subtilis chromosomal genetic map. We have cloned and sequenced the hem genes at this location. The sequenced region contains six open reading frames: ponA, hemE, hemH, hemY, ORFA, and ORFB. The ponA gene product shows over 30% sequence identity to penicillin-binding proteins 1A of Escherichia coli, Streptococcus pneumoniae, and Streptococcus oralis and probably has a role in cell wall metabolism. The hemE gene was identified from amino acid sequence comparisons as encoding uroporphyrinogen III decarboxylase. The hemH gene was identified by enzyme activity analysis of the HemH protein expressed in E. coli. It encodes a water-soluble ferrochelatase which catalyzes the final step in protoheme IX synthesis, the insertion of ferrous iron into protoporphyrin IX. The function of the hemY gene product was not elucidated, but mutation analysis shows that it is required for a late step in protoheme IX synthesis. The hemY gene probably encodes an enzyme with coproporphyrinogen III oxidase or protoporphyrinogen IX oxidase activity or both of these activities. Inactivation of the ORFA and ORFB genes did not block protoheme IX synthesis. Preliminary evidence for a hemEHY mRNA was obtained, and a promoter region located in front of hemE was identified. From these combined results we conclude that the hemEHY gene cluster encodes enzymes for the synthesis of protoheme IX from uroporphyrinogen III and probably constitutes an operon. PMID- 1459958 TI - CzcR and CzcD, gene products affecting regulation of resistance to cobalt, zinc, and cadmium (czc system) in Alcaligenes eutrophus. AB - The czcR gene, one of the two control genes responsible for induction of resistance to Co2+, Zn2+, and Cd2+ (czc system) in the Alcaligenes eutrophus plasmid pMOL30, was cloned and characterized. The 1,376-bp sequence upstream of the czcCBAD structural genes encodes a 41.4-kDa protein, the czcR gene product, transcribed in the opposite direction of that of the czcCBAD genes. The putative CzcR polypeptide (355 amino acid residues) contains 11 cysteine and 14 histidine residues which might form metal cation-binding sites. A czcC::lacZ reporter gene translational fusion was constructed, inserted into plasmid pMOL30 in A. eutrophus, and expressed under the control of CzcR. Zn2+, Co2+, and Cd2+, as well as Ni2+, Cu2+, Hg2+, and Mn2+ and even Al3+, served as inducers of beta galactosidase activity. Besides the CzcR protein, the membrane-bound CzcD protein was essential for induction of czc. The CzcR and CzcD proteins display no sequence similarity to two-component regulatory systems of a sensor and a response activator type; however, CzcD has 34% identity with the ZRC-1 protein, which mediates zinc resistance in Saccharomyces cerevisiae (A. Kamizomo, M. Nishizawa, Y. Teranishi, K. Murata, and A. Kimura, Mol. Gen. Genet. 219:161-167, 1989). PMID- 1459959 TI - Menaquinone (vitamin K2) biosynthesis: evidence that the Escherichia coli menD gene encodes both 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid synthase and alpha-ketoglutarate decarboxylase activities. AB - The formation of 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid (SHCHC), the first identified intermediate in the menaquinone biosynthetic pathway, requires two reactions. They are the decarboxylation of alpha ketoglutarate by an alpha-ketoglutarate decarboxylase, which results in the formation of succinic semialdehyde-thiamine PPi (TPP) anion, and the addition of the succinic semialdehyde-TPP anion to isochorismate carried out by the enzyme SHCHC synthase. Evidence is provided to support the conclusion that both enzymatic activities are encoded by an extended menD gene which is capable of generating a bifunctional 69-kDa protein. Consistent with the requirement for TPP in the decarboxylation of alpha-ketoglutarate, the translated amino acid sequence contains the characteristic TPP-binding motif present in all well-characterized TPP-requiring enzymes. PMID- 1459961 TI - Three clustered origins of replication in a promiscuous-plasmid replicon and their differential use in a PolA+ strain and a delta PolA strain of Escherichia coli K-12. AB - A 1,197-bp region of the broad-host-range plasmid pCU1 is adequate for its replication. Analysis of replicating molecules containing this region reveals three clustered origins of vegetative replication and replication proceeds bidirectionally from each in a theta mode. In an Escherichia coli polymerase I deletion mutant, utilization of one of these three origins was not detected. The potentiality for origin utilization may therefore be a determinant of replicon host range. PMID- 1459960 TI - Definition of a minimal plasmid stabilization system from the broad-host-range plasmid RK2. AB - The stable inheritance of the broad-host-range plasmid RK2 is due at least in part to functions within a region located at coordinates 32.8 to 35.9 kb, termed the RK2 par locus. This locus encodes four previously identified genes in two operons (parCBA and parD; M. Gerlitz, O. Hrabak, and H. Schwab, J. Bacteriol. 172:6194-6203, 1990, and R. C. Roberts, R. Burioni, and D. R. Helinski, J. Bacteriol. 172:6204-6216, 1990). The parCBA operon is functional in resolving plasmid multimers to monomers. Analysis of the plasmid stabilization capacity of deletions within this region, however, indicates that this multimer resolution operon is required for stabilization only in certain Escherichia coli strains and under specific growth conditions. The deletion analysis further allowed a redefinition of the minimal functional region as 790 bp in length, consisting of the parD gene (243 bp) and its promoter as well as sequences downstream of parD. This minimal region stabilizes an RK2-derived minireplicon in several different gram-negative bacteria and, at least in E. coli, in a vector-independent manner. By insertional mutagenesis, both the parD gene and downstream (3') regions were found to be required for plasmid stabilization. The downstream DNA sequence contained an open reading frame which was subsequently shown by transcriptional and translational fusions to encode a protein with a predicted size of 11,698 Da, designated ParE. Since the parDE operon requires the presence of the parCBA operon for efficient stabilization under certain growth conditions, the potential role of multimer resolution in plasmid stabilization was tested by substituting the ColE1 cer site for the parCBA operon. While the cer site did function to resolve plasmid multimers, it was not sufficient to restore stabilization activity to the parDE operon under growth conditions that require the parCBA operon for plasmid stability. This suggests that plasmid stabilization by the RK2 par locus relies on a complex mechanism, representing a multifaceted stabilization system of which multimer resolution is a conditionally dispensable component, and that the function(s) encoded by the parDE operon is essential. PMID- 1459962 TI - The carboxy-terminal 14 amino acids of phage lambda N protein are dispensable for transcription antitermination. AB - The analogous N proteins encoded by lambdoid bacteriophages lambda, 21, and 22 are very different in amino acid sequence, except at their carboxy-terminal ends. Since N lambda remains functional despite the deletion of most of its terminal region of homology to N21, that region of homology cannot represent a region of conserved function. PMID- 1459963 TI - Properties of purified sporlets produced by spoII mutants of Bacillus subtilis. AB - A number of abortively disporic spoII mutants of Bacillus subtilis released their forespore compartments (termed stage II sporlets) after mother cell lysis during sporulation in nutrient exhaustion or resuspension media. Stage II sporlets were viable and contained levels of ATP and a number of enzymes similar to those in cells 2 to 3 h after sporulation. However, stage II sporlets carried out essentially no macromolecular synthesis, a result suggesting that they were in a quiescent state. The nucleoid of these quiescent stage II sporlets was significantly condensed relative to that in the original vegetative cells, as was previously found to take place 1 to 2 h after initiation of sporulation (B. Setlow, N. Magill, P. Febbroriello, L. Nakhimousky, D. E. Koppel, and P. Setlow, J. Bacteriol. 173:6270-6278, 1991). Stage II sporlets may be a useful model system for analysis of forespore properties early in stage II of sporulation. PMID- 1459964 TI - Rate maintenance of cell division in Escherichia coli B/r: analysis of a simple nutritional shift-down. AB - A competitive (nonmetabolizable) inhibitor of glucose uptake, alpha methylglucoside, was used to limit the growth of Escherichia coli. Cell division during such a nutritional shift-down was studied in batch cultures and with the "baby-machine" technique. Following a brief delay, the rate of division was maintained for 60 to 70 min in batch cultures and for an extended period in the baby machine. Decreases in cell size were due, in part, to a possible reduction in the mass per chromosome origin at the time of replication initiation and a shorter time interval between initiation and the subsequent division. These unusual findings suggest that this method for abrupt change in growth rate without modifying repression patterns is useful for studying the control of various aspects of the bacterial cell. PMID- 1459965 TI - Presence of methylated adenine in GATC sequences in chromosomal DNAs from Campylobacter species. AB - We digested chromosomal DNAs from 12 Campylobacter strains (C. jejuni, 4 strains; C. coli, 2 strains; C. fetus subsp. fetus, 2 strains; C. hyointestinalis, 2 strains; and C. upsaliensis, 2 strains) and from 4 Helicobacter strains (H. pylori, 2 strains; and H. mustelae, 2 strains) with HindIII, SstI, BamHI, DpnI, MboI, and Sau3AI. Restriction fragments were then separated by electrophoresis in 1% agarose or 10% polyacrylamide gels. Only DNAs from three Campylobacter species (C. jejuni, C. coli, and C. upsaliensis) were digested with DpnI (an enzyme that recognizes only methylated adenine in GATC sequences). We used MboI and Sau3AI to confirm these findings. PMID- 1459966 TI - Structural and functional properties of the p60 proteins from different Listeria species. AB - The major extracellular protein p60 of Listeria monocytogenes seems to be required for this microorganism's adherence to and invasion of 3T6 mouse fibroblasts but not for adherence to human epithelial Caco-2 cells. Western blot analysis with polyclonal antibodies against p60 of L. monocytogenes indicated the presence of cross-reacting proteins in the culture supernatants of all Listeria species. Protein p60 of L. monocytogenes could restore adhesion of the L. monocytogenes mutant RIII (impaired in the synthesis of p60) to mouse fibroblasts more efficiently than that of Listeria grayi. The amino acid sequences of the p60 related proteins of L. innocua, L. ivanovii, L. seeligeri, L. welshimeri, and L. grayi indicated highly conserved regions of about 120 amino acids at both the N terminal and the C-terminal ends. The middle portions of these proteins, consisting of about 240 amino acids, varied considerably. These parts include the repeat domain consisting of repetitions of Thr (T) and Asn (N) which was present only, albeit in different arrangements, in the p60 proteins of L. monocytogenes and L. innocua. The p60-related proteins of L. grayi, L. ivanovii, L. seeligeri, and L. welshimeri each contained an insertion of 54 amino acids which was absent in the p60 proteins of L. monocytogenes and L. innocua. PMID- 1459967 TI - Evidence that the hemolysin/bacteriocin phenotype of Enterococcus faecalis subsp. zymogenes can be determined by plasmids in different incompatibility groups as well as by the chromosome. AB - The hemolysin (Hly/Bac) determinant in strains of Enterococcus faecalis was found to be present on plasmids in different incompatibility groups (conferring different sex pheromone responses) as well as on the chromosome. Of 33 Hly/Bac plasmids identified in clinical isolates, the related pheromone for 30 was cAD1; the related pheromone for another two (pYI1 and pYI3) or one (pYI2) was cOB1 or cY12, respectively. The representative Hly/Bac plasmids pAD1, pYI1, pOB1, and pYI2, which responded to pheromones cAD1, cOB1, cOB1, and cYI2, respectively, were compatible with one another. As additions to the incompatibility group IncHly of pAD1, groups for pOB1, pYI1, and pYI2 were designated IncHlyII, IncHlyIII, and IncHlyIV, respectively. Eleven of the 30 plasmids conferring a response to cAD1 were very similar to pAD1 on the basis of their restriction endonuclease profiles. EcoRI fragment D, F, or H containing parts of the Hly/Bac gene(s) of pAD1 hybridized to similar EcoRI fragments from each of the other three representatives of incompatibility groups (i.e., pOB1, pYI1, and pYI2) and to homologous DNA representing the chromosome of the plasmid-free Hly/Bac strain YI6-1. PMID- 1459968 TI - Treatment outcome of obsessive compulsive disorder with comorbid social phobia. AB - BACKGROUND: Treatment of obsessive compulsive disorder (OCD) with serotonin reuptake blockers has been demonstrated effective in 50% to 60% of patients in open and placebo-controlled studies. However, some reports indicate that comorbid Axis II psychopathology, including avoidant personality disorder, and deficiency of social skills could be predictors of a poor response to treatment in OCD patients. METHOD: A retrospective review elicited 12 patients who met DSM-III-R diagnostic criteria for both OCD and social phobia and were treated in our clinic last year with adequate trials of serotonin reuptake blockers or MAOIs. RESULTS: Only 3 (27%) of the 11 patients treated with serotonin reuptake blockers had a substantial improvement of OCD symptoms. Among them, only 1 (11%) of 9 patients with generalized subtype of social phobia versus 2 (100%) of 2 patients with the nongeneralized subtype responded to serotonin reuptake blockers. Four (80%) of 5 patients with comorbid generalized social phobia receiving phenelzine had marked improvement of OCD symptoms. In general, response of social phobia occurred parallel to that of OCD. CONCLUSION: Comorbid generalized social phobia seems to be associated with a poor response to serotonin reuptake blockers in OCD patients. Deficient social skills, as well as distinct biological mechanisms, may be involved. MAOIs might be an effective alternative medication in refractory cases. Larger and controlled studies are needed to define the implications of the association of OCD and social phobia. PMID- 1459969 TI - Night terrors in adults: phenomenology and relationship to psychopathology. AB - BACKGROUND: Night terrors have been classically described in children. Night terrors occurring in adults have been linked to psychopathology. Recent descriptions of sleep panic attacks have raised questions about their relationship to night terrors. METHOD: Evaluations from a medically affiliated sleep disorders program were reviewed to identify adult patients presenting with events consistent with night terrors. Eleven patients were identified, 10 of whom had polysomnographic evaluation, and their records were reviewed for information relevant to night terrors and psychiatric symptoms. Six of these patients were available for further assessment which included inquiry regarding sleep events, a Structured Clinical Interview (SCID) for psychiatric disorders, and the Millon Clinical Multiaxial Inventory II (MCMI-II) for personality-related measurements. RESULTS: In the original sample, night terror episodes featured confused behaviors, motor activity, and absent or fragmented recall. Polysomnography documented arousals from slow wave sleep in 9 of 10 patients. All of the original patients reported psychiatric symptoms. All 6 patients who received the subsequent structured evaluation met lifetime criteria for Axis I conditions (most commonly affective and substance use disorders) and had elevated scores on the personality scales of the MCMI-II. Night terrors were not limited to psychiatric episodes. CONCLUSION: Night terrors occur in adults that are similar to episodes described in children. While distinct from sleep panic attacks, night terrors appear to occur in adults with histories of psychopathology. PMID- 1459970 TI - Restraint, seclusion, and clozapine. AB - BACKGROUND: The effects of clozapine, an unconventional neuroleptic drug, on the use of restraint and seclusion in patients have not been extensively reported on in the United States. METHOD: The records of 107 patients receiving clozapine in Missouri state mental hospitals were reviewed over a 13-month period for frequency and duration of restraint and seclusion. RESULTS: During clozapine treatment, patients had fewer episodes of restraint and seclusion than previously. The duration of restraints and seclusions also decreased, starting the second month after the initiation of clozapine treatment. CONCLUSION: For patients who were restrained or secluded before clozapine treatment, the decrease in the number and duration of restraint and seclusion episodes was dramatic. PMID- 1459971 TI - The effect of enalapril on serum lithium levels in healthy men. AB - BACKGROUND: Several authors have recently described the development of lithium toxicity after the addition of angiotensin-converting enzyme inhibitors to a stable lithium regimen. This pilot study was designed to systematically investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on the serum level of lithium. METHOD: In a 26-day outpatient study, nine healthy men took lithium for 10 days, lithium and enalapril for 10 days, and lithium alone again for 6 days. Serum lithium levels were measured while patients were taking lithium alone and while they were taking the lithium/enalapril combination. RESULTS: There were no statistically significant differences between mean serum lithium level during treatment with lithium alone and during treatment with the lithium/enalapril combination. However, one subject showed a 31% increase in serum lithium level after enalapril was added. CONCLUSION: Although no statistically significant differences between mean serum lithium level during treatment either with lithium alone or with lithium/enalapril were found, it is possible that the low dose of enalapril and low serum lithium levels employed for subject safety may have resulted in a type II statistical error. If enalapril doses or initial serum lithium levels were similar to those described in case reports, a significant difference in mean serum lithium levels may have been observed. While a predictable interaction between lithium and enalapril probably does not occur in all patients, factors such as enalapril dose, serum lithium level before addition of enalapril, or the presence of heart disease may make such an interaction more likely. At the levels of lithium and enalapril used in this study, elevated serum lithium concentration does not appear to be a universal event, but physicians must exercise appropriate caution. PMID- 1459972 TI - Personality and clinical characteristics in patients with trichotillomania. AB - BACKGROUND: Trichotillomania, a disorder of self-directed hair pulling, has been the subject of few systematic studies. Although personality characteristics and disorders are often noted to coexist with trichotillomania, no thorough assessment of comorbidity with DSM-III-R Axis II disorders has been published. The present study was conducted to evaluate personality disorders and other personality characteristics in a large outpatient population of trichotillomanics and to compare these findings with those in a nontrichotillomanic comparison group. METHOD: Forty-eight outpatient female trichotillomanics were evaluated with the Structured Interview for DSM-III-R Personality Disorders (SIDP-R) and the revised version of the Minnesota Multiphasic Personality Inventory (MMPI-2). Personality disorders and personality cluster symptom scores from the SIDP-R and MMPI-2 scales were compared with those derived from a comparison group of 48 age matched female outpatient psychiatric patients. RESULTS: Forty-two percent of the trichotillomanic group met criteria for a personality disorder. The only statistically significant difference in frequency of diagnoses between the trichotillomanic and comparison groups was a greater frequency of borderline personality disorder in the comparison group. Trichotillomanics demonstrated significantly less SIDP-R cluster A personality symptoms as well as less depression and better psychological adjustment on the MMPI-2. CONCLUSION: Our study suggests that no particular personality disorder or trait characterizes female trichotillomanics. Female trichotillomanics seeking psychiatric intervention appear to have better psychological adjustment and less psychopathology in general than other psychiatric outpatients. PMID- 1459973 TI - Catatonia in a patient with AIDS-related dementia. PMID- 1459974 TI - AIDS-related psychosis with catatonia responding to low-dose lorazepam. PMID- 1459975 TI - High incidence of haloperidol decanoate injection site reactions. PMID- 1459976 TI - Dangerous driving and eating disorders. PMID- 1459977 TI - Nifedipine and nonresponse to antidepressants. PMID- 1459978 TI - Comparison of SPECT applications in neurology and psychiatry. AB - The following presentation provides an overview of SPECT brain imaging applications in both neurologic and psychiatric disorders. Specific findings in cerebrovascular disease, dementia, and epilepsy are described in order to highlight the role SPECT plays in distinguishing primary organic disease from primary psychopathology. Through case examples, new applications of three dimensional SPECT rCBF imaging that could play a major role in defining CNS network abnormalities in major depressive disorder and obsessive compulsive disorder are elucidated. The role of network imaging analysis across groups in psychiatric subjects is contrasted to its roles in neurologic disorders. The degree to which both neurologic and psychiatric pathology seen on SPECT exceeds that observed through structural modalities is defined. PMID- 1459979 TI - Regional cerebral blood flow imaging with SPECT in psychiatric disease: focus on schizophrenia, anxiety disorders, and substance abuse. AB - In psychiatric disorders where gross brain structure is preserved, as confirmed through computed tomography and magnetic resonance imaging, neuroSPECT imaging provides further diagnostic insight by demonstrating abnormal brain function related to disturbances in perfusion or metabolism. This paper will focus on how the psychiatrist may incorporate SPECT brain imaging into the diagnostic process for schizophrenia, where frontal lobe hypoperfusion and hypometabolism have been demonstrated; for obsessive compulsive disorder, which has been linked to abnormalities in the basal ganglia, anterior cingulate gyrus, and orbital frontal cortex; and for substance abuse, where use of cocaine can be associated with cortical and subcortical perfusion defects. PMID- 1459980 TI - Current and future applications of SPECT in clinical psychiatry. AB - Over the past 10 years several studies have been conducted in psychiatric and neurologic patients with single photon emission computed tomography (SPECT) to determine if patterns of brain dysfunction exist that characterize the different mental diseases. Although there has not been any finding that can be referred to as specific for a particular disease, SPECT studies have been able to demonstrate evidence of brain dysfunction in patients who, when tested with other means, showed no evidence of brain abnormalities. In this manuscript, the current and future applications of SPECT in the clinical practice of psychiatry are analyzed. PMID- 1459981 TI - Neuroreceptor imaging with SPECT. AB - Single photon emission computed tomography (SPECT) imaging can provide useful measurements of brain receptors and endogenous neurotransmitters and may have significant experimental and clinical applications. This presentation reviews the use of SPECT for neuroreceptor imaging. Studies of receptors for benzodiazepines, dopamine D2 agents, and dopamine reuptake sites will be used to exemplify the capabilities of SPECT. Tracers labeled with the radioisotope 125I have high affinity, high brain uptake, and high ratios of specific to nonspecific binding. Imaging studies of human and nonhuman primate brain will be presented, and the potential clinical applicability of these agents will be discussed. PMID- 1459982 TI - An introduction and overview to clinical applications of neuroSPECT in psychiatry. AB - This brief paper introduces the reader to the materials presented in other manuscripts of this issue of The Journal of Clinical Psychiatry. Single photon emission computed tomography (SPECT) is a dynamic brain imaging technique that grew out of the evolution of increasingly more sophisticated approaches to understanding the pathophysiology and biology of neurologic and psychiatric disorders over the past two decades. SPECT is a practical tool that is more available than positron emission tomography (PET), which is found primarily at academic centers. While SPECT has drawbacks that relate to levels of resolution and the possible impact of altered brain physiology on interpretation of results, it offers advantages of decreased cost, the need for less intensively trained technicians, and the ability to carry out clinical testing in facilities lacking a cyclotron. These factors raise the hope of more routine use of this imaging technique in clinical settings related to cognitive disorders, schizophrenia, affective disorders, and problems associated with substance use. PMID- 1459983 TI - Brain SPECT imaging and psychiatry. AB - To provide a basis for using neuroSPECT (single photon emission computerized tomography) in the evaluation of psychiatric disorders, this presentation will focus on recent developments in this field. Newer advances in cerebral SPECT instrumentation and radiopharmaceuticals and the potential impact on the evaluation of psychiatric patients will be discussed. PMID- 1459984 TI - Extremophiles: fascinating organisms with surprising capabilities. PMID- 1459985 TI - Energetics of methanogenesis studied in vesicular systems. AB - Methanogenesis is restricted to a group of prokaryotic microorganisms which thrive in strictly anaerobic habitats where they play an indispensable role in the anaerobic food chain. Methanogenic bacteria possess a number of unique cofactors and coenzymes that play an important role in their specialized metabolism. Methanogenesis from a number of simple substrates such as H2 + CO2, formate, methanol, methylamines, and acetate is associated with the generation of transmembrane electrochemical gradients of protons and sodium ions which serve as driving force for a number of processes such as the synthesis of ATP via an ATP synthase, reverse electron transfer, and solute uptake. Several unique reactions of the methanogenic pathways have been identified that are involved in energy transduction. Their role and importance for the methanogenic metabolism are described. PMID- 1459986 TI - Photophosphorylation elements in halobacteria: an A-type ATP synthase and bacterial rhodopsins. AB - Photophosphorylation in halobacteria is carried out by two rather simple elements: an A-type ATP synthase and light-driven ion-pumping bacterial rhodopsins. The unique features of halobacterial ATP synthase, mostly common to archaebacteria (A-type), and of new members of the bacteriorhodopsin family are introduced along with studies performed in the authors' laboratory. This is the story of how we found that the A-type ATP synthase is close to V-type ATPase but far from F-type ATPase, although all three ATPases are believed to have the same ancestor. Archaerhodopsins, the new members of the proton-pumping retinal proteins, were found in Australian halobacteria and have been used in a comparative study of bacterial rhodopsins. PMID- 1459987 TI - Structures of archaebacterial membrane lipids. AB - Structural data on archaebacterial lipids is presented with emphasis on the ether lipids of the methanogens. These ether lipids normally account for 80-95% of the membrane lipids with the remaining 5-20% of neutral squalenes and other isoprenoids. Genus-specific combinations of various lipid core structures found in methanogens include diether-tetraether, dietherhydroxydiether, or diether macrocyclic diether-tetraether lipid moieties. Some species have only the standard diether core lipid, but none are known with predominantly tetraether lipids as found in certain sulfur-dependent archaebacteria. The relative proportions of these lipid cores are known to vary in relation to growth conditions in Methanococcus jannaschii and Methanobacterium thermoautotrophicum. Polar headgroups in glycosidic or phosphodiester linkage to the sn-1 or sn-1' carbons of glycerol consist of polyols, carbohydrates, and amino compounds. The available structural data indicate a close similarity among the polar lipids synthesized within the species of the same genus. Detection of lipid molecular ions by mass spectrometry of total polar lipid extracts is a promising technique to provide valuable comparative data. Since these lipid structures are stable within the extreme environments that many archaebacteria inhabit, there may be specific applications for their use in biotechnology. PMID- 1459988 TI - Structural features of archaebacterial cell envelopes. AB - Regularly arrayed surface (glyco) proteins--often referred to as S layers--are a common feature of the cell envelopes of almost all archaebacteria. We have selected some examples (Halobacterium, Sulfolobus, Thermoproteus, Pyrobaculum, Staphylothermus), and we describe the structure of their surface layers as revealed primarily by electron crystallography. In spite of a considerable diversity in shapes and dimensions, some common structural features emerge from the comparison. The glycoprotein arrays are composed of oligomeric units which are anchored in the plasma membrane; extended spacer or linker domains maintain the bulk of the more or less porous surface layers at a constant distance above the membrane surface, thus creating a quasi-periplasmic compartment. Functions ascribed to surface layers, such as compartmentalization, shape maintenance and determination, and adhesion are discussed. PMID- 1459989 TI - Function and biosynthesis of gas vesicles in halophilic Archaea. AB - The proteinaceous gas vesicles produced by various microorganisms including halophilic Archaea are hollow, gas-filled structures with a hydrophobic inner and a hydrophilic outer surface. The structural components of gas vesicles and their biosynthesis are still under investigation; an 8-kDa polypeptide appears to be the major constituent of the gas-vesicle envelope. Genetic analysis of the halobacterial gas-vesicle synthesis revealed an unexpected complexity: about 14 genes organized in three transcription units are involved in gas-vesicle structure, assembly, and gene regulation. Here we describe the comparison of three different genomic regions encoding gas vesicles in Halobacterium salinarium (p-vac and c-vac regions) and Haloferax mediterranei (mc-vac region) and speculate on the function of the gene products involved in gas-vesicle synthesis. PMID- 1459990 TI - Energy transduction and transport processes in thermophilic bacteria. AB - Bacterial growth at the extremes of temperature has remained a fascinating aspect in the study of membrane function and structure. The stability of the integral membrane proteins of thermophiles make them particularly amenable to study. Respiratory enzymes of thermophiles appear to be functionally similar to the mesophilic enzymes but differ in their thermostability and unusual high turnover rates. Energy coupling at extreme temperatures seems inefficient as suggested by the high maintenance coefficients and the high permeability of the cell membrane to protons. Nevertheless, membranes maintain their structure at these extremes through changes in fatty acid acyl chain composition. Archaebacteria synthesize novel membrane-spanning lipids with unique physical characteristics. Thermophiles have adapted to life at extreme temperatures by using sodium ions rather than protons as coupling ions in solute transport. Genetic and biochemical studies of these systems now reveal fundamental principles of such adaptations. The recent development of reconstitution techniques using membrane-spanning lipids allows a rigorous biochemical characterization of membrane proteins of extreme thermophiles in their natural environment. PMID- 1459991 TI - Correlation between active form and dimeric structure of mitochondrial nicotinamide nucleotide transhydrogenase from beef heart. AB - The active form of purified mitochondrial nicotinamide nucleotide transhydrogenase from beef heart was investigated by crosslinking with dimethylsuberimidate and SDS-PAGE, with or without pretreatment with the inactivating detergent Triton X-100. In the absence of detergent, crosslinked isomers of the dimeric form of 208-235 kDa were obtained. Addition of detergent led to the simultaneous loss of the dimers and the bulk of the activity. Removal of the detergent led to a partial restoration of both activity and the dimeric forms. The results suggest that the active form is a dimer, and that the detergent-dependent conversion to the largely inactive monomer is reversible. It is proposed that the mechanism of inactivation of transhydrogenase by Triton X 100 involves a disruption of essential hydrophobic interactions between the membrane-spanning regions of the monomers. PMID- 1459992 TI - Differential scanning calorimetry study of glycogen phosphorylase b-detergent interactions. AB - The overall thermal denaturation of glycogen phosphorylase b is irreversible and our results conform to the theoretical prediction of a reversible process followed by a slower irreversible process. The basic thermodynamic parameters of glycogen phosphorylase b denaturation have been worked out and found to be: critical temperature 57.0 +/- 0.5 degrees C, transition half-width 8 +/- 1 degrees C, and calorimetric enthalpy change and Van't Hoff enthalpy change of the denaturation process 450 +/- 50 and 105 +/- 15 kcal/mol of enzyme monomer, respectively, at pH 7.4. These parameters have been found to be largely altered by the detergents octylglucoside, cholate, and deoxycholate at or below their critical micelle concentration, but not by Triton X-100 nor by lecithin liposomes. Organic solvents, such as dimethyl sulfoxide and methanol, and the presence of sarcoplasmic reticulum membranes produces an alteration of the denaturation thermogram of glycogen phosphorylase b similar to that produced by the above-mentioned detergents. These results allow us to hypothesize that hydrophobic domains of glycogen phosphorylase b are involved in its association to sarcoplasmic reticulum membranes in the sarcoplasmic reticulum/glycogenolytic complex of mammalian skeletal muscle. PMID- 1459993 TI - Characterization of the inhibitor sensitivity of the coenzyme A transport system in isolated rat heart mitochondria. AB - The effect of protein labeling agents on coenzyme A (CoA) transport into isolated rat heart mitochondria was studied. CoA transport was substantially inhibited by sulfhydryl reagents (mersalyl, pCMB) as well as by the tyrosine-selective reagent N-acetylimidazole. The effect of pCMB was reversed by DTT. Moreover, CoA uptake was completely abolished by agents selective for lysine and amino terminal residues (pyridoxal 5-phosphate, dansyl chloride). In contrast arginine-selective reagents (2, 3-butanedione, phenylglyoxal) caused considerably less inhibition of CoA uptake. Moreover, partial inhibition of transport was observed with the stilbene disulfonic acid derivatives DIDS and SITS. Finally, measurement of the effects of the labeling agents on the mitochondrial membrane potential indicated that the inhibition of CoA transport into mitochondria is not a secondary effect that arises from an alteration in the electric potential gradient across the inner mitochondrial membrane. These results provide the first information on the types of amino acid residues that may be essential to the CoA transport mechanism and provide additional support for the existence of a CoA transport protein within the mitochondrial inner membrane. Furthermore, the identification of effective inhibitors of the CoA transport system will greatly facilitate the functional reconstitution of this transporter in a proteoliposomal system following its solubilization and purification. PMID- 1459994 TI - Tyrosine kinases and tyrosine-based activation motifs. Current research on activation via the T cell antigen receptor. PMID- 1459995 TI - Negative regulation of hepatocyte growth factor gene expression in human lung fibroblasts and leukemic cells by transforming growth factor-beta 1 and glucocorticoids. AB - Hepatocyte growth factor (HGF), a mesenchymal-derived factor which regulates growth, motility, and morphogenesis of epithelial and endothelial cells, functions as a hepatotrophic and renotrophic factor for regeneration of the liver and kidney. We have now obtained evidence that transforming growth factor-beta 1 (TGF-beta 1) and glucocorticoids are negative regulators for HGF gene expression. When TGF-beta 1 or dexamethasone was added to cultures of MRC-5 human embryonic lung fibroblasts and HL-60 human promyelocytic leukemic cells, the amount of HGF secreted into the culture medium was inhibited to 30-40% of that of control cultures by 10 ng/ml TGF-beta 1 and to 40-50% by 10(-6) M dexamethasone. The inhibitory effect of TGF-beta 1 and dexamethasone on HGF synthesis in MRC-5 cells was additive, thereby suggesting that TGF-beta 1 and dexamethasone exert effects through distinct mechanisms. Hydrocortisone also inhibited HGF synthesis with the same potency as dexamethasone; however, testosterone, estriol, and beta-estradiol had no effect. The rate of HGF synthesis in MRC-5 cells, as measured by pulse labeling with [35S]methionine and subsequent immunoprecipitation, was suppressed to 30-40% of the control with 10 ng/ml TGF-beta 1, and to 30-45% by 10(-6) M dexamethasone. HGF mRNA levels in MRC-5 cells and HL-60 cells were dose dependently suppressed by TGF-beta 1 and dexamethasone; 10 ng/ml TGF-beta 1 suppressed HGF mRNA levels to 32% and 35% of control culture, respectively, in MRC-5 cells and HL-60 cells, and 10(-6) M dexamethasone suppressed to 43% and 38%, respectively. Thus, TGF-beta 1 and glucocorticoids seem to inhibit HGF synthesis by suppressing the expression of the HGF gene. We propose that a negative regulation of HGF gene expression by TGF-beta 1 or glucocorticoids may be involved in physiological or pathological processes during tissue regeneration. PMID- 1459996 TI - Thrombospondin 1 and thrombospondin 2 are expressed as both homo- and heterotrimers. AB - There exist two distinct thrombospondin molecules (designated TSP1 and TSP2) which are encoded by separate genes. TSP1 is a trimeric cell surface and extracellular matrix molecule. Sequence comparison reveals that the 2 cysteines involved in interchain disulfide linkage and trimer assembly in TSP1 are conserved in TSP2 (Laherty, C. D., O'Rourke, K., Wolf, F. W., Katz, R., Seldin, M. F., and Dixit, V. M. (1992) J. Biol. Chem. 267, 3274-3281). Swiss 3T3 fibroblasts express both TSP1 and TSP2, and, therefore, an important question is whether TSP in such cells is expressed as homotrimers or as heterotrimers. We find that Swiss 3T3 cells and epithelial cells transfected with TSP expression vectors express both homo- and heterotrimeric forms of TSP. In addition, homotrimeric TSP2 has a lower affinity for heparin than homotrimeric TSP1. Thus, the heparin affinity of TSP can be modulated by the expression of TSP as homo- or heterotrimers. PMID- 1459997 TI - Inhibition of glyoxalase I by the enediol mimic S-(N-hydroxy-N methylcarbamoyl)glutathione. The possible basis of a tumor-selective anticancer strategy. AB - In principle, competitive inhibitors of glyoxalase I that also serve as substrates for the thioester hydrolase glyoxalase II might function as tumor selective anti-cancer agents, given the role of these enzymes in removing cytotoxic methylglyoxal from cells and the observation that glyoxalase II activity is abnormally low in some types of cancer cells. In support of the feasibility of this anticancer strategy, an inhibitor of this type has been synthesized by a thioester-interchange reaction between glutathione and N-hydroxy N-methylcarbamate 4-chlorophenyl ester to give S-(N-hydroxy-N methylcarbamoyl)glutathione (1). This compound was designed to be a tight-binding inhibitor of glyoxalase I, on the basis of its stereoelectronic similarity to the enediol(ate) intermediate that forms along the reaction pathway of this enzyme. Indeed, 1 is a competitive inhibitor of yeast glyoxalase I, with an inhibition constant (Ki = 68 microM) that is approximately 30-fold lower than that reported for S-D-lactoylglutathione and approximately 7-fold lower than the Km for glutathione-methylglyoxal thiohemiacetal. In addition, 1 is a substrate for bovine liver glyoxalase II, with a Km (0.48 mM) approximately equal to that of the normal substrate S-D-lactoyglutathione and a kcat approximately 2 x 10(-5) fold that of the normal substrate. Membrane transport studies show that 1 can be delivered into human erythrocytes (used here as a model cell) either by direct diffusion of 1 across the cell membrane or by more rapid diffusion of the glycylethyl ester of 1 across the cell membrane, followed by the catalyzed hydrolysis of the ester to give 1. PMID- 1459998 TI - Determinants for DNA-binding site recognition by the glucocorticoid receptor. AB - The glucocorticoid receptor binds with high specificity to glucocorticoid response elements, discriminating them from other closely related binding sites. Three amino acids in the recognition alpha-helix of the DNA-binding domain of the receptor are primarily responsible for this specific DNA binding activity. In this study we analyze in detail how these residues determine the specific DNA binding by studying a series of mutant glucocorticoid receptor DNA-binding domains containing all combinations of glucocorticoid and estrogen receptor specific residues at these positions. Statistical analysis of the results enables us to create models describing the association between amino acids and base pairs. Several strategies appear to be used in accomplishing discrimination between the glucocorticoid and estrogen response elements. Single residues (i.e., Val-443 in the glucocorticoid receptor and Glu-439 in the estrogen receptor) appear to form both positive contacts with specific base pairs in the cognate binding site and negative contacts in the non-cognate site. In the glucocorticoid receptor Ser-440 is pleiotropically negative for all sites tested but the negative effect is stronger for the estrogen response element thus contributing to binding site discrimination. Furthermore, combinations of amino acids appear to act synergistically, most often causing a reduction in binding to non-cognate sites. PMID- 1459999 TI - Characterization and purification of a novel transcriptional repressor from HeLa cell nuclear extracts recognizing the negative regulatory element region of human immunodeficiency virus-1 long terminal repeat. AB - Cellular transcription factors play critical roles in regulating human immunodeficiency virus (HIV) gene transcription, although the precise mechanism(s) defining their roles are not well established. Primarily it has been suggested that sequence-specific interaction of trans-activating proteins with cis-acting DNA elements plays a crucial role in regulating the target genes. The negative regulatory element (NRE) of HIV-1 long terminal repeat (LTR) is one such defined region that has been reported to down-regulate LTR-directed HIV gene expression. Information regarding the role of this region in the regulation of HIV expression is lacking. Here we describe an attempt to further characterize the role of NRE cis-elements and define any sequence-specific interaction with cellular factors. Using gel mobility shift DNA-binding and Southwestern blot assays, we have mapped a distinct region of NRE (-290 to -260, a 30-base pair (bp) domain of NRE-A) sequences of HIV-1 LTR, which recognizes a specific DNA binding protein from HeLa cell nuclear extracts. This factor is a 38-kDa polypeptide which can be affinity-purified to near homogeneity by this 30-bp specific oligonucleotide in affinity chromatography. The cellular factor from HeLa cell nuclear extract exhibits specific interaction only with the 30-bp NRE-A domain of HIV-1 LTR and acts as a strong transcriptional repressor/inhibitor molecule in the DNA-protein gel binding, as well as in vitro transcriptional studies with the nuclear extracts from cells with productive HIV-1 infection. To our knowledge, this is the first report of a factor recognizing a distinct segment within NRE that has been shown to exert an inhibitory effect on transcriptionally active DNA-protein "pre-initiation" complex formation, suggesting a possible role in HIV-1 gene regulation. PMID- 1460000 TI - Ultraviolet-induced dimerization of non-adjacent pyrimidines in poly[d(A-T)]. AB - The DNA photoproduct responsible for the ultraviolet (UV) light-induced -1 frameshift mutation remains unknown. We recently identified a UV photoproduct consisting of a cyclobutane dimer occurring between non-adjacent thymine residues in the same strand, [sequence: see text] and proposed that replication across this unrepaired photoproduct might result in a -1 frameshift mutation since the intervening base is extrahelical. Until now this novel photoproduct has only been identified in single-stranded DNA polymers and does not occur in UV-irradiated double-stranded polymers due to conformational restraint. This observation suggested that this photoproduct could only occur in vivo in chromosomal sites that were single-stranded. In the current work the cis-syn dithymine cyclobutane dimer has been identified in the self-complementary polymer poly[d(A-T)] when UV irradiated in solution conditions (concentrated manganese chloride or 60% ethanol plus trace salts) wherein this polymer remains double-stranded but the double helix is partially destabilized. Taken together, the current findings suggest that dipyrimidine photoproducts between non-adjacent residues on the same strand could occur in vivo in double-stranded, but partially destabilized, DNA. PMID- 1460001 TI - Cytotoxicity of momordin-folate conjugates in cultured human cells. AB - We have shown previously that macromolecules can be nondestructively delivered into cultured cells via folate receptor-mediated endocytosis if the macromolecules are conjugated to folic acid prior to addition to receptor-bearing cells (Leamon, C.P., and Low, P. S. (1991) Proc. Natl. Acad. Sci. U. S. A. 88, 5572-5576). Although an intracellular destination of the folate-linked proteins could be easily documented, the spatial resolution of the earlier data was insufficient to evaluate whether any endocytosed material was delivered into the cytosol. To resolve this issue, a folate-toxin conjugate was constructed using the impermeable ribosome-inactivating protein, momordin. Diminution of [3H]leucine incorporation into newly synthesized protein was then employed as a quantitative measure of the entry of the toxin into the cytosol. In studies with both HeLa and KB cells, cellular protein synthesis was found to be inhibited in a time- and concentration-dependent manner by the momordin-folate conjugate, but not by the underivatized toxin. IC50 values centered around 10(-9) M for the folate-linked samples. These observations provide direct evidence that folate conjugates not only reach the cytosol, but do so in a functionally active form. PMID- 1460002 TI - Sorbitol dehydrogenase from Bacillus subtilis. Purification, characterization, and gene cloning. AB - Cloning of the sorbitol dehydrogenase gene (gutB) from Bacillus subtilis offers an excellent system for studying zinc binding, substrate specificity, and catalytic mechanism of this enzyme through protein engineering. As a first step to clone gutB, B. subtilis sorbitol dehydrogenase has been purified to homogeneity and characterized. It is a tetrameric enzyme with a molecular mass of 38 kDa for each subunit. Atomic absorption analysis shows the presence of 1 mol of zinc atom/subunit. Substrate specificity and stereospecificity of the enzyme toward C-2 and C-4 of hexitols were established. Sequence of the first 31 amino acids was determined, and a set of oligonucleotide probes was designed for gene cloning. A positive clone carrying a 5-kilobase pair HindIII insert was isolated and sequenced. Sequence alignment indicated that the deduced amino acid sequence of B. subtilis sorbitol dehydrogenase shows 36% identity in sequence with the liver sorbitol dehydrogenase from sheep, rat, and human. In reference to the sequence of alcohol dehydrogenase, two potential zinc binding sites were identified. Sequence information related to the structure-function relationships of the enzyme is discussed. PMID- 1460003 TI - The AMP-binding domain on adenylate kinase. Evidence for a conformational change during binary-to-ternary complex formation via photoaffinity labeling analyses. AB - The topological location of the nucleotide substrate binding environments on adenylate kinase has been explored with the fluorescent molecule [4 benzoyl]benzoyl-1-amidofluorescein (BzAF) and the nucleotide analog 3'-O-[4 benzoyl]benzoyl-ATP (BzATP), which are site-directed photoaffinity probes that bind covalently at the individual nucleotide sites. The MgBzATP substituted for MgATP as a substrate for this enzyme, whereas BzAF, which is neither a substrate nor a nucleotide, behaved as a competitive inhibitor for each nucleotide site independently. BzAF could be directed specifically to either of the nucleotide sites by near saturation of the second site with its natural nucleotide substrate. Using this second site blocking approach, each nucleotide site, in turn, could be protected competitively from BzAF-induced photoinhibition by the presence of its natural substrate. This strategy showed that under photolysis, the Kd(BzAF) of 0.1 mM (for the MgATP site) and 0.2 mM (for the AMP site) were nearly identical with the Km(app) values determined for MgATP and AMP, respectively. Pseudo first-order photolysis kinetics with [3H]BzAF revealed covalent binding stoichiometries for full inhibition of 1 mol of probe/mol of enzyme at either site. Thus, we prepared the binary complex ([3H]BzAF-enzyme) by photo-labeling the MgATP site-blocked enzyme with [3H]BzAf to 1:1 molar stoichiometry. Tryptic digestion followed by partial sequencing of the [3H]BzAF labeled enzyme disclosed that BzAF was bound specifically within the peptide span Gly64-->Arg77. This amino acid domain therefore probably constitutes the neighborhood identifiable with AMP binding. Furthermore, we also achieved double photocovalent labeling of adenylate kinase with both photoprobes, by first cross linking with approximately 1 mol of MgBzATP, followed by approximately 0.9 mol of [3H]BzAF, thus generating a ternary covalent complex. Comparison of the fluorescence of the binary species and the ternary (BzATP-enzyme-[3H]BzAF) complex revealed altered fluorescence emission profiles, which could indicate that a conformational change occurs during formation of the ternary (or transition state) complex. PMID- 1460004 TI - The influence of flanking sequence on the O-glycosylation of threonine in vitro. AB - To investigate the influence of flanking amino acid sequence on the O glycosylation of a single threonine residue in vitro, we have examined a series of 52 related peptides. The substrates were based upon a sequence from human von Willebrand factor which is known to be glycosylated in vivo (-6PHMAQVTVGPGL+5). Each residue of the parent peptide was substituted, in turn, with isoleucine, alanine, proline, glutamic acid, or arginine. Peptides were glycosylated using a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase purified 15,000-fold from bovine colostrum by chromatography on DEAE-Sephacel, SP-Sephadex, Sephacryl S-300, Affi-Gel Blue, and 5-mercuri-UDP-GalNAc thiopropyl-Sepharose. Single amino acid changes in the sequences flanking the threonine could profoundly alter the glycosylation of the substrate peptides. Substitution of any amino acid tested at positions +3, -3, and -2 markedly decreased O-glycosylation, as did the presence of a charged residue at position -1. The substitution of amino acids at the other positions of the peptide substrate had little effect on the incorporation of GalNAc. Statistical analysis of sequences flanking known glycosylated threonine and serine residues suggests that they should be glycosylated with equal efficiency in the same sequence context (O'Connell et al., 1991). However, the bovine colostrum transferase failed to glycosylate a peptide derived from human erythropoietin which contains a serine that is glycosylated in vivo ( 5PPDAASAAPLR+5). When a threonine was substituted for the serine in this peptide (-5PPDAATAAPLR+5), the substrate proved to be an excellent acceptor of GalNAc. These observations indicate that although flanking amino acid sequence is important for the O-glycosylation of specific hydroxyamino acids, discrete threonine- and serine-specific transferases may exist. PMID- 1460005 TI - Characterization of a novel, potent, and specific inhibitor of serine palmitoyltransferase. AB - We have examined the mechanism of action of two natural products identified as broad spectrum antifungal agents (VanMiddlesworth, F., Dufresne, C., Wincott, F. E., Mosley, R. T., and Wilson, K. E. (1992) Tetrahedron Lett., in press; VanMiddlesworth, F., Giacobbe, R. A., Lopez, M. Garrity, G., Bland, J. A., Bartizal, K., Fromtling, R. A., Polishook, J., Zweerink, M. M., Edison, A. M., Rozdilsky, W., Wilson, K. E., and Monaghan, R. L. (1992) J. Antibiot. (Tokyo) 45, 861-867), designated sphingofungin B (2S-amino-3R,4R,5S,14-tetrahydroxyeicos-6 enoic acid) and sphingofungin C (2S-amino-5S-acetoxy-3R,4R,14-trihydroxyeicos-6 enoic acid), and find they are potent specific inhibitors of serine palmitoyltransferase, which catalyze the committed step of sphingolipid biosynthesis. We used Saccharomyces cerevisiae as a model to investigate the mechanism of the antifungal activity of these compounds. Macromolecular synthesis was not immediately affected by either sphingofungin B or C, synthesis continued for 60-90 min following the addition of drug to growing cultures. Significant loss of viability with sphingofungins required growing cultures and began only after several hours, with greater than 99.9% of drug-treated cells non-viable after 24 h. No lysis or other gross changes in cell morphology were observed in drug-treated cells. The structural similarity of sphingofungin B and C to sphingosine and phytosphingosine prompted us to investigate their effects on sphingolipid synthesis. Nanomolar levels of the drugs inhibited the incorporation of [3H]inositol into sphingolipid before incorporation into the sphingolipid precursor, phosphatidylinositol was affected, suggesting specific inhibition of sphingolipid synthesis. This hypothesis was confirmed by experiments in which the growth inhibitory activity of both drugs was completely ablated by the addition of phytosphingosine, dihydrosphingosine, or ketodihydrosphingosine to the culture medium. Reversal of antifungal activity by ketodihydrosphingosine suggested that serine palmitoyltransferase could be the actual target of these compounds. Direct evidence for this hypothesis was the observation of inhibition of serine palmitoyltransferase activity in crude membrane preparations at nanomolar concentrations of each drug. The potent inhibition of serine palmitoyltransferase coupled with the apparent lack of effect of these compounds on other cellular functions suggests that sphingofungin B and C will prove to be important new tools for studying the role of sphingolipids in yeast and perhaps in other organisms. PMID- 1460006 TI - Inhibition of carbonic anhydrases I and II by N-unsubstituted carbamate esters. AB - We previously showed that the zinc metalloenzyme carbonic anhydrases (CA I and II isozymes) bind "neutral" amides and related compounds as anions through coordination of their deprotonated amide nitrogen to the active site zinc (Rogers, J. I., Mukherjee, J., and Khalifah, R. G. (1987) Biochemistry 26, 5672 5679). Urethan, the ethyl carbamate ester, was among such compounds. The present study was designed to test whether other N-unsubstituted carbamate esters of pharmacological interest (as sedatives, hypnotics, anxiolytics, and skeletal muscle relaxants) were capable of binding to CA in the same manner. We studied the interaction of human CA I and II with urethan, phenyl carbamate, ethinamate, meprobamate, and methocarbamol. Phenyl carbamate studies were greatly complicated by its uncatalyzed hydrolysis via an elimination mechanism to form cyanate, a powerful CA inhibitor. In general, the compounds display: 1) slow on-off inhibition binding kinetics in the seconds range, 2) maximal inhibitor affinity at alkaline pH, and 3) characteristic three-band visible spectra of their complexes with cobalt-substituted CA I. These properties are shared with the previously studied amide inhibitors and are taken as evidence that the deprotonated carbamate nitrogen coordinates to the active site metal ion. CA I appeared to bind carbamate esters more tightly than CA II, an unusual 1000-fold selectivity being seen in the case of methocarbamol. The inhibition by these drugs is not sufficiently strong to implicate CA I and II in their mechanism of action. However, it does suggest the possible existence of previously unsuspected similarities between binding to CA and to their physiological receptors or targets, particularly the involvement of zinc. PMID- 1460007 TI - Structural and functional relationships in DnaK and DnaK756 heat-shock proteins from Escherichia coli. AB - The secondary structures of DnaK and the mutant DnaK756 heat-shock proteins from Escherichia coli have been investigated by Fourier transform infrared spectroscopy. The analysis of infrared data showed that DnaK and DnaK756 proteins have different secondary structures that are not affected by the presence of ATP or beta, gamma-methyleneadenosine 5'-triphosphate. The infrared data indicate also that the tertiary structures of DnaK and DnaK756 proteins are different and that DnaK protein undergoes conformational changes in its tertiary structure not only during binding of ATP but also during ATP hydrolysis. Using fluorescence spectroscopy of a single tryptophan located in the N-terminal domain of DnaK protein and fluorescence of 1,1'-bis(4-anilino)naphthalene-5,5'-disulfonic acid, which interacts with hydrophobic domains of DnaK protein, we were able to distinguish between two conformational states of DnaK protein. After binding of triphosphonucleotides, the C-terminal domain of DnaK protein changes in tertiary structure in such a way that fewer hydrophobic segments are exposed on the surface of the protein. After ATP hydrolysis, the number of hydrophobic segments on the surface of the protein is further reduced, and moreover the tertiary structure of the N-terminal domain of the protein changes. These data are discussed in terms of structural and functional relationships of both DnaK and DnaK756 proteins. PMID- 1460008 TI - Functional delineation of the Ca(2+)-deficient EF-hand in cardiac muscle, with genetically engineered cardiac-skeletal chimeric troponin C. AB - Cardiac and fast skeletal isoforms of TnC each comprise four putative EF-hand (helix-loop-helix) motifs as potential Ca(2+)-binding sites (sites 1-4), except that site 1 in cardiac TnC is deficient in Ca2+ coordination. In skeletal TnC, the N-terminal sites 1 and 2 are both essential for the trigger mechanism of the contraction switch. However, the mechanism in cardiac muscle is unsettled; it is obscure whether the cardiac site 1 is functionally inert due to calcium deficiency and consequently site 2 is the lone trigger site, or whether sites 1 and 2 perform interactively despite the impairment. These possibilities were addressed by mutagenizing site 1 in skeletal TnC to mimic the cardiac response. In one mutant (STnC-1), two selected Ca(2+)-ligands were abolished. In another (C1/S chimera), 41 N-terminal residues from cardiac TnC were spliced to STnC. The Ca(2+)-binding capacities as well as skinned fiber responses were measured. The STnC-1 derivative failed to switch on contraction. In contrast, the chimeric construct expressed close to full contractile potential in myocardium (74 +/- 3% Po; Po = maximal tension) and also the manifest cardiac phenotype. By devising supplemental chimeric constructs, cardiac-type N-terminal overhang together with cardiac-type EF-hand for site 1 both were found essential for the phenotype. We conclude that cardiac TnC site 1 is actively engaged in the trigger mechanism and in fact dominates the phenotype despite the inability to chelate Ca2+. The N terminal overhang also participates in this mechanism, which is a novel finding. The conclusion that a non-chelating site functions interactively with a proximal site in cardiac TnC may have wider significance, inasmuch as similar pairings of disparate EF-hands are of common occurrence. PMID- 1460009 TI - Enhancement of the chemical and antimicrobial properties of subtilin by site directed mutagenesis. AB - Subtilin and nisin are gene-encoded antibiotic peptides that are ribosomally synthesized by Bacillus subtilis and Lactococcus lactis, respectively. Gene encoded antibiotics are unique in that their structures can be manipulated by mutagenesis of their structural genes. Although subtilin and nisin share considerable structural homology, subtilin has a greater tendency than nisin to undergo spontaneous inactivation. This inactivation is a accompanied by chemical modification of the dehydroalanine at position 5 (DHA5) with a kinetic first order t1/2 of 0.8 days. It was hypothesized that the R group carboxyl of Glu4 in subtilin participates in the chemical modification of the adjacent DHA5. Noting that nisin has Ile at position 4, site-directed mutagenesis was used to change Glu4 of subtilin to Ile, in order to eliminate this carboxyl-group participation. The DHA5 of this mutant subtilin (E4I-subtilin) underwent modification with a t1/2 of 48 days, which is 57-fold slower than natural subtilin, and the rate of loss of biological activity dropped by a like amount. These results suggest that an intact DHA5 is critical for subtilin activity against bacterial spore outgrowth. A double mutant of subtilin, in which the DHA5 residue of E4I-subtilin was mutated to Ala was devoid of detectable inhibition against spore outgrowth. The specific activity of E4I-subtilin was 3-4-fold higher than natural subtilin, suggesting that an increase in the hydrophobicity of the N-terminal end of the molecule enhances activity. These are the first mutants of subtilin that have been reported, and E4I-subtilin is the first example of any lantibiotic whose properties have been improved by mutagenesis. In order to carry out the mutagenesis, a host-vector pair was constructed that permits a deletion replacement in which the natural subtilin gene is replaced by the mutant gene at the normal location in the chromosome. This maintains normal gene dosage and regulatory responses, as well as eliminates ambiguities caused by expression of the normal and mutant genes in the same cell. PMID- 1460010 TI - Human lipoprotein lipase: the loop covering the catalytic site is essential for interaction with lipid substrates. AB - Lipoprotein lipase (LPL), a key enzyme which initiates the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins, consists of multiple functional domains which are necessary for normal activity. The catalytic domain of LPL mediates the esterase function of the enzyme but separate lipid binding sites have been proposed to be involved in the interaction of LPL with emulsified lipid substrates at the water-lipid interface. Like pancreatic lipase (PL), LPL contains a surface loop covering the catalytic pocket that may modulate access of the substrate to the active site of the enzyme. Secondary structural analysis of this loop reveals a helix-turn-helix motif with two short amphipathic helices that have hydrophobic moments of 0.64 and 0.68. In order to investigate the role of the loop in the initial interaction of LPL with its substrate, we utilized site-directed mutagenesis to generate eight constructs in which the amphipathic properties of the loop were altered and expressed them in human embryonal kidney-293 cells. Reducing the amphiphilicity without changing the predicted secondary structure of the loop abolished the ability of the lipase to hydrolyze emulsified, long chain fatty acid triglycerides (triolein) but not the water soluble substrate tributyrin. Replacing the loop of LPL with the loop of hepatic lipase, which differs in 15 of 22 amino acids but is also amphiphilic, led to the expression of an enzyme that retained both triolein and tributyrin hydrolyzing activity. Substitution of the LPL loop by a short four amino acid peptide, which may allow more direct access to the active site than the 22 amino acid loop, enhanced hydrolysis of short chain fatty acid triglycerides by more than 2-fold, while the ability to hydrolyze emulsified substrates was abolished. Thus, disruption of the amphipathic structure of the LPL loop selectively decreases the hydrolysis of emulsified lipid substrate without affecting the esterase or catalytic function of the enzyme. These studies establish that the loop with its two amphipathic helices is essential for hydrolysis of long chain fatty acid substrate by LPL providing new insight into the role of the LPL loop in lipid-substrate interactions. We propose that the interaction between the lipoprotein substrates and the amphipathic helices within this loop may in part determine lipase substrate specificity. PMID- 1460011 TI - Evidence that 24- and 27-hydroxylation are not involved in the cholesterol induced down-regulation of hydroxymethylglutaryl-CoA reductase in mouse liver. AB - Several authors have suggested that 27-hydroxycholesterol may be an important physiological regulator of cholesterol homeostasis. In the present study we investigated the possibility that 24- or 27-hydroxylation of cholesterol is of importance for the down-regulation of hydroxymethylglutaryl (HMG)-CoA reductase in mouse liver induced by dietary cholesterol. Using an accurate method based on isotope dilution-mass spectrometry with deuterated internal standards, we were able to detect significant levels of both 24- and 27-hydroxycholesterol in liver homogenates from normal mice. Feeding cholesterol, 2% for 4 days, increased the levels by 80 and 30%, respectively. No significant hepatic levels of 25 hydroxycholesterol could be demonstrated in untreated mice, and the level of this steroid in cholesterol-treated mice was just above the detection limit. Mouse liver mitochondria were able to catalyze 24- as well as 27-hydroxylation, but not 25-hydroxylation of cholesterol. There was no such conversion in liver microsomes. When using 24-2H2- or 23,23,24,24,25-2H5-labeled cholesterol as substrate a kinetic isotope effect of about 4.5 was observed for the mitochondrial 24-hydroxylation. When using 26,26,26,27,27,27-2H6-labeled cholesterol as substrate a kinetic isotope effect of about 2.5 was observed for the 27-hydroxylation. Use of those deuterium-labeled cholesterol species thus allowed a specific suppression of the rate of 24- and 27-hydroxylation. Feeding mice with 0.05% unlabeled pure cholesterol in the diet for 24 h inhibited the hepatic HMG-CoA reductase activity by about 50%. The same degree of suppression was obtained after feeding with 23,23,24,24,25-2H5- and 26,26,26,27,27,27-2H6 labeled cholesterol. Were mitochondrial 24- and 27-hydroxylation of importance, one would expect reduced suppression of HMG-CoA reductase when feeding deuterated cholesterol, due to the isotope effects. As this was not the case, it is concluded that neither 24-hydroxylation nor 27-hydroxylation are critical for the cholesterol-induced down-regulation of HMG-CoA reductase in mouse liver. PMID- 1460012 TI - Inhibition of agonist-induced activation of phospholipase C following poxvirus infection. AB - Recent studies indicate that viruses may influence polyphosphoinositide levels. This study has examined the effects of vaccinia virus infection on phospholipase C activity. Infection of BS-C-1 cells, an African Green Monkey kidney cell line, or A431 cells, a human carcinoma cell line, with vaccinia virus inhibits receptor mediated phospholipase C activation. As a consequence, agonist-mediated Ca2+ mobilization in BS-C-1 cells also was inhibited by vaccinia virus infection. Alleviation of the inhibition of phospholipase C activation was observed in vaccinia virus-infected cells treated with cycloheximide without influencing uninfected cells. Treatment of infected cells with alpha-amanitin, an inhibitor of host mRNA synthesis but not virus mRNA synthesis, failed to alleviate the inhibition of phospholipase C activation. Together these results suggest that a virus-encoded gene product mediates the inhibition of phospholipase C activation without the need of a virus-induced host factor. Analysis of the processes involved in the formation of inositol (1,4,5)-trisphosphate and mobilization of intracellular Ca2+ indicate that the vaccinia virus gene product exerts its inhibitory effects at the level of phospholipase C activity. This may occur by either directly reducing the amount of phospholipase C, reducing the specific activity of phospholipase C, or by inhibiting the association of phospholipase C with its substrate, phosphatidylinositol 4,5-bisphosphate. PMID- 1460013 TI - NMR constrained solution structures for laminin peptide 11. Analogs define structural requirements for inhibition of tumor cell invasion of basement membrane matrix. AB - Peptide 11, CDPGYIGSR-NH2, is a segment of laminin which blocks tumor cell invasion. A high affinity laminin receptor in tumor cells is thought to be blocked by the carboxyl-terminal YIGSR, and conformational energy calculations suggest that the glycine in YIGSR allows an important conformational bend. We replaced the YIGSR glycine residue in peptide 11 with either D-alanine or L alanine to allow or disfavor the proposed glycine bend. We found the Gly7-->D Ala7 analog to be equal to peptide 11 in inhibiting tumor cell invasion of basement membrane matrix. The Gly7-->L-Ala7 analog was much less capable of invasion inhibition. Two-dimensional 1H-1H NMR was used to study the solution conformations of the peptide 11 analogs. NOESY experiments revealed close NH-NH contacts in peptide 11 and the D-Ala7 analog, but not in the L-Ala7 analog. Molecular dynamics generated low energy structures with excellent NOE agreement for peptide 11 and its analogs. Both peptide 11 and the D-Ala7 analog, but not the less active L-Ala7 analog, were predicted to have similar bends around Gly7 or D-Ala7. These results suggest that a bend in the YIGSR region of peptide 11 may be important for the binding of laminin to its metastasis-associated receptor. PMID- 1460014 TI - Aplysia peptide neurotransmitters beta-bag cell peptide, Phe-Met-Arg-Phe-amide, and small cardioexcitatory peptide B are rapidly degraded by a leucine aminopeptidase-like activity in hemolymph. AB - We have been investigating the role of proteolytic enzymes in the inactivation of peptide neurotransmitters in the marine snail Aplysia. Previous studies (Squire, C. R., Talebian, M., Menon, J. G., Dekruyff, S. D., Lee, T. D., Shively, J. E., and Rothman, B. S. (1991) J. Biol. Chem. 266, 22355-22363) showed that neuroactive fragments of the neurotransmitter alpha-bag cell peptide (alpha-BCP) were rapidly degraded (t1/2 = 0.5-2.7 min) in plasma, hemolymph that had been cleared by centrifugation. Degradation was caused by one or more enzymes resembling mammalian leucine amino-peptidase (LAP, EC 3.4.11.1). In this report we show that three other Aplysia peptide neurotransmitters, beta-BCP(1-5) (Arg Leu-Arg-Phe-His), FMRFa (Phe-Met-Arg-Phe-amide), and SCPB(1-9) (Met-Asn-Tyr-Leu Ala-Phe-Pro-Arg-Met-amide) are rapidly degraded (t1/2 = 0.3-2.4 min) in plasma by apparently the same LAP-like enzyme(s). Our findings strongly suggest that the LAP-like enzyme(s), by means of its broad substrate specificity and access to the extracellular spaces of the nervous system in vivo, plays a significant role in the inactivation of many Aplysia peptide neurotransmitters, and they raise the possibility that proteolytic enzymes in the extracellular fluid contribute significantly to the inactivation of peptide neurotransmitters in other animal species. PMID- 1460015 TI - Ferroxidase kinetics of horse spleen apoferritin. AB - Protein ferroxidase site(s), which catalyze the reaction between ferrous ion and dioxygen, have long been thought to play a role in core formation in ferritin; however, the mechanism of the reaction has never been studied in detail. In the present work, the enzymatic activity of ferritin was examined using oximetry, the net Fe2+ oxidation reaction being as follows. [formula: see text] The reaction exhibits saturation kinetics with respect to both Fe2+ and O2 (apparent Michaelis constants: Km,Fe = 0.35 +/- 0.01 mM and Km,O2 = 0.14 +/- 0.03 mM). The enzyme has a turnover number kcat = 80 +/- 3 min-1 at 20 degrees C with maximal activity at pH 7. The kinetics are discussed in terms of two mechanisms, one involving monomeric and the other dimeric iron protein complexes. In both instances Fe(II) oxidation occurs in 1-electron steps. Zinc(II) is a competitive inhibitor of iron(II) oxidation at Zn2+/apoprotein ratios > or = 6 (inhibitor constant KI,Zn = 0.067 +/- 0.011 mM) but appears to be a noncompetitive inhibitor at lower ratios (< or = 2), indicating the presence of more than one type of zinc binding site on the protein. At increments of 50 Fe2+/protein or less, all of the iron is oxidized via the protein ferroxidase site(s), independent of the amount of core already present. However, when larger increments are employed, some iron oxidation appears to occur on the surface of the mineral core. The results of these studies emphasize the role of the protein shell in all phases of core growth and confirm the presence of a functionally important catalytic site in ferritin in addition to other binding sites on the protein for iron. PMID- 1460016 TI - Rat hepatonuclear factor PS-1 regulates tissue-specific activity of the S14 promoter in vitro. AB - We have previously identified a rat hepatonuclear factor, PS-1 that binds to the thyroid hormone responsive gene, S14. To determine whether PS-1 is involved in regulating tissue-specific expression of the S14 gene, we have correlated the DNA binding activity of PS-1 with mRNA-S14 expression in a variety of tissues. Gel retardation analysis revealed a pattern of binding to the recognition site that was characteristic of tissues with high levels of mRNA-S14, a different pattern was found in tissues which do not express the gene. Competition studies using mutant oligonucleotides showed that the first 4 nucleotides and the CAAT motif contained within the PS-1 recognition sequence are essential for protein binding. C/EBP, a CCAAT-transcription factor binds to the PS-1 recognition site thus raising the possibility that both C/EBP and PS-1 may belong to the same family of proteins. Next we used a cell-free transcription assay to measure activity of a template, pS14-GFC(-72), that contained the PS-1 sequence. The pS14-GFC(-72) template was active in hepatonuclear extracts but deletion of or competition with the PS-1 binding sequence rendered the construct inactive. A template containing three PS-1 binding sequences increased S14 promoter activity by 12- to 13-fold. In nuclear extracts from spleen and testis, relative S14 promoter activity was only 2% of that in the liver, this observation mimicked closely in vivo expression of the gene. Mixing together extracts from liver and spleen in varying proportions, prior to incubation with S14 template, yielded a linear increase in S14 promoter activity that correlated with the amount of liver extract in the reaction. This finding is consistent with the absence of an essential factor or factors in spleen that is/are required for S14 promoter activity in vitro. In summary, PS-1 binds to a DNA sequence that contains a CAAT motif and appears to play a critical role in determining tissue-specific activity of the S14 promoter in vitro. PMID- 1460017 TI - Autophosphorylation of the catalytic subunit of cAMP-dependent protein kinase. AB - The catalytic subunit of cAMP-dependent protein kinase contains two stable phosphorylation sites, Thr-197 and Ser-338 (Shoji, S., Titani, K., Demaille, J. G., and Fischer, E. H. (1979) J. Biol. Chem. 254, 6211-6214). Thr-197 is very resistant to dephosphorylation and thus cannot typically be autophosphorylated in vitro once the stable subunit is formed. Ser-338 is slowly dephosphorylated and can be rephosphorylated autocatalytically. In addition to these two stable phosphorylation sites, a new site of autophosphorylation, Ser-10, was identified. Phosphorylation at Ser-10 does not have a major effect on activity, and phosphates from Ser-10 or Ser-338 are not transferred to physiological substrates such as the type II regulatory subunit. Autophosphorylation at Ser-10 is associated with one of the two major isoelectric variants of the catalytic subunit. The form having the more acidic pI can be autophosphorylated at Ser-10 while the more basic form of the catalytic subunit cannot. Phosphorylation at Ser 10 does not account for the two isoenzyme forms. Since the reason for two isoelectric variants of the catalytic subunit is still unknown, it is not possible to provide a structural basis for the difference in accessibility of Ser 10 to phosphorylation. Either Ser-10 is not accessible in the more basic form of the catalytic subunit or some other type of post- or cotranslational modification causes Ser-10 to be a poor substrate. Whether the myristoyl group at the amino terminal Gly is important for Ser-10 autophosphorylation remains to be established. The isoenzyme forms of the catalytic subunit do not correspond to the gene products coded for by the C alpha and C beta genes. PMID- 1460018 TI - Oxidation-reduction properties of Escherichia coli thioredoxin reductase altered at each active site cysteine residue. AB - Thioredoxin is a small oxidation-reduction (redox) mediator protein. Its reduction by NADPH is catalyzed by the flavoenzyme thioredoxin reductase. Site directed mutagenesis has provided forms of the reductase in which Cys135 and Cys138 have each been changed to a serine residue (Prongay, A. J., Engelke, D. R., and Williams, C. H., Jr. (1989) J. Biol. Chem. 264, 2656-2664). Cys135 and Cys138 form the redox-active disulfide in the oxidized enzyme. The redox properties of the two altered forms of Escherichia coli thioredoxin reductase have been determined from pH 6.0 to 9.0. Photoreduction of TRR(Ser135,Cys138) produces the blue, neutral semiquinone species, which disproportionates (Kf = 0.73) to an apparent maximum of 29% of the total enzyme as the semiquinone. In contrast, the semiquinone formed on TRR(Cys135,Ser138) during a photoreductive titration does not disproportionate and 70% of the enzyme is stabilized as the semiquinione. Reductive titrations have demonstrated that 1 mol of sodium dithionite (2 electrons)/mol of FAD is required to fully reduce TRR(Ser135,Cys138) whereas 2 mol of dithionite/mol of FAD are required to fully reduce TRR(Cys135,Ser138). The oxidation-reduction midpoint potentials for the 1 electron and 2-electron reductions of TRR(Ser135,Cys138) have been determined by NADH/NAD+ titrations in the presence of a mediator, benzyl viologen. The midpoint potential for the 2-electron reduction of TRR(Ser135,Cys138) is -280 mV, at pH 7.0 and 20 degrees C. Thus, the redox potential is similar to that of the FAD/FADH2 couple in the dithiol form of wild type enzyme, -270 mV (corrected to 20 degrees C) (O'Donnell, M. E., and Williams, C. H., Jr. (1983) J. Biol. Chem. 258, 13795-13805). The delta Em/delta pH is -57.1 mV, which corresponds to a proton stoichiometry of 2 H+/2 e-.A maximum of 19% of the enzyme forms a stable semiquinone species during the titration, and the potentials for the oxidized enzyme/semiquinone couple, E2, and the semiquinone/reduced enzyme couple, E1, are -306 and -256 mV, respectively, at pH 7.0 and 20 degrees C. These studies provide evidence that the residue at position 138 exerts a greater effect on the FAD than does the residue at position 135. PMID- 1460019 TI - Post-translational processing of an O-glycosylated protein, the human CD8 glycoprotein, during the intracellular transport to the plasma membrane. AB - The biosynthesis of human CD8 glycoprotein in transfected rat epithelial cells produces an unglycosylated precursor, an intermediate species only initially O glycosylated, and a doublet mature form carrying neutral and sialylated O-linked oligosaccharides with the core-2 structure (Pascale, M. C., Malagolini, N., Serafini-Cessi, F., Migliaccio, G., Leone, A., and Bonatti, S. (1992) J. Biol. Chem. 267, 9940-9947). In this study the most relevant post-translational events: dimerization, addition of the first O-linked GalNAc, fulfillment of O-linked chains, as well as expression of involved glycosyltransferases, have been examined and correlated with the localization and transit rate of CD8 through the exocytic pathway. The glycosyltransferase activities measured in rat epithelial cells transfected with human CD8 DNA are entirely consistent with the primary structure assigned to CD8 oligosaccharides. The half-time of appearance of the initially O-glycosylated precursor and mature form was estimated to be 4 and 14 min, respectively, and the half-time for delivery of mature CD8 to the cell surface was found to be about 30 min, indicating a very fast routing. Pulse experiments with [35S]cysteine at 37 degrees C followed by chase-periods at low temperatures showed that folding/dimerization occurs before routing to the Golgi apparatus, whereas the addiction of O-linked GalNAc appears to take place later, very likely in cis-Golgi cisternae. Treatment of cells with monensin accumulated the intermediate CD8 form carrying non-elongated O-linked GalNAc, whereas brefeldin A treatment produced a sialylated glycoprotein species with a mobility faster than the mature CD8. These results indicate that the two drugs affect assembly of O-linked chains at different time of their processing. PMID- 1460020 TI - Molecular cloning, cDNA sequence, and bacterial expression of human glutamine:fructose-6-phosphate amidotransferase. AB - Glutamine:fructose-6-phosphate amidotransferase (GFAT) has recently been shown to be an insulin-regulated enzyme that plays a key role in the induction of insulin resistance in cultured cells. As a first step in understanding the molecular regulation of this enzyme the human form of this enzyme has been cloned and the functional protein has been expressed in Escherichia coli. A 3.1-kilobase cDNA was isolated which contains the complete coding region of 681 amino acids. Expression of the cDNA in E. coli produced a protein of approximately 77 kDa and increased GFAT activity 4.5-fold over endogenous bacterial levels. Recombinant GFAT activity was inhibited 51% by UDP-GlcNAc whereas bacterial GFAT activity was insensitive to inhibition by UDP-GlcNAc. On the basis of these results we conclude that: 1) functional human GFAT protein was expressed, and 2) the cloned human cDNA encodes both the catalytic and regulatory domains of GFAT since the recombinant GFAT was sensitive to UDP-GlcNAc. Overall, the development of cloned GFAT molecular probes should provide new insights into the development of insulin resistance by allowing quantitation of GFAT mRNA levels in pathophysiological states such as non-insulin-dependent diabetes mellitus and obesity. PMID- 1460021 TI - Osteogenic protein-2. A new member of the transforming growth factor-beta superfamily expressed early in embryogenesis. AB - Osteogenic protein-2, OP-2, a new member of the transforming growth factor-beta (TGF-beta) superfamily, closely related to the osteogenic/bone morphogenetic proteins, was discovered in mouse embryo and human hippocampus cDNA libraries. The TGF-beta domain of OP-2 shows 74% identity to OP-1, 75% to Vgr-1, and 76% to BMP-5, hence OP-2 may also have bone inductive activity. The genomic locus of OP 2 has seven exons, like OP-1, and spans more than 27 kilobases (kb). In the C terminal TGF-beta domain, OP-2 has a unique additional cysteine. Mouse embryos express relatively high levels of OP-2 mRNA at 8 days, two species of 3 and 5 kb. A careful study of mRNA expression of the osteogenic proteins in specific organs revealed discrete mRNA species for BMP-3, BMP-4, BMP-5, and BMP-6/Vgr-1 in lung or liver of young and adult mice. OP-1 is expressed in kidney; however, OP-2 and BMP-2 mRNAs were not detected in any organs studied, suggesting an early developmental role. PMID- 1460022 TI - Structure and expression of neutrophil gelatinase cDNA. Identity with type IV collagenase from HT1080 cells. AB - Neutrophils synthesize and store intracellularly a 92-kDa type IV collagenase (gelatinase), the primary structure of which is unknown. We designed a primer based on the highly conserved cysteine-switch region of metalloproteinases and employed the polymerase chain reaction to generate a probe of the human neutrophil gelatinase (HNG) gene. This probe was used to clone the cDNA encoding HNG by screening a chronic granulocytic leukemia cDNA library. In vitro translation of the cDNA-derived HNG mRNA yielded a major product of 78 kDa and smaller autolytically activated or degraded products, all of which were recognized by anti-HNG antibody. The HNG cDNA sequence is nearly identical to that encoding a 92-kDa gelatinase secreted by HT1080 cells. In addition, primer extension and S1 analysis reveal that the above two gelatinase transcripts have similar initiation sites. The HNG cDNA hybridized to a 2.8-kilobase mRNA from chronic granulocytic leukemia cells. HNG mRNA expression was absent from uninduced HL60 cells and from HL60 cells induced to granulocytic maturation with Me2SO. However, unlike other neutrophil secondary granule genes, HNG mRNA was detected in HL60 cells induced to monocytic maturation with 12-O tetradecanoylphorbol 13-acetate. This suggests that the HNG gene may be subject to differential control pathways in two related but distinct hematopoietic lineages. PMID- 1460023 TI - Palmitylation of neuromodulin (GAP-43) is not required for phosphorylation by protein kinase C. AB - Neuromodulin (also designated GAP-43, B-50, and F-1) is a prominent protein kinase C substrate attached to the membranes of neuronal growth cones during development and to presynaptic membranes in discrete subsets of adult synapses. In this study, we have examined the relationship between the attachment of neuromodulin to membranes and its phosphorylation by protein kinase C. To address this issue, we have compared wild-type and mutant neuromodulins expressed in cells that normally lack the protein. Wild-type neuromodulin expressed in Chinese hamster ovary cells was associated with membranes, incorporated [3H]palmitic acid, and was phosphorylated in response to phorbol ester treatment. Substitution of serine 41, the in vitro protein kinase C site, abolished the phorbol ester response, indicating that serine 41 serves as the sole protein kinase C phosphorylation site in vivo. Substitution of the putative fatty acylation sites, cysteines 3 and 4, abolished membrane association as well as [3H]palmitic acid labeling of neuromodulin. Fatty acylation therefore appears to serve as the mechanism for anchoring neuromodulin to membranes. Surprisingly, the soluble cysteine substitution mutant was phosphorylated by protein kinase C at a rate indistinguishable from that of the wild-type protein. Therefore, membrane association may not be required for the phosphorylation of neuromodulin by protein kinase C. PMID- 1460024 TI - Interconversion of GRP78/BiP. A novel event in the action of Pasteurella multocida toxin, bombesin, and platelet-derived growth factor. AB - Incubation of Swiss 3T3 cells with [2-3H]adenine, as in other cell types, reveals the ADP-ribosylation of GRP78 (the 78-kDa glucose-regulated protein, also known as BiP, the immunoglobulin heavy chain-binding protein), a resident endoplasmic reticulum protein that assists in the processing of proteins destined for secretion or cell surface expression. Here we show that Pasteurella multocida toxin, a potent growth factor for cultured fibroblasts, decreased the ADP ribosylation of GRP78/BiP to 16 +/- 6% of the control value (n = 23). The action of the toxin occurred after a lag period, was blocked by lysosomotrophic agents, and potentiated by increased incubation time (ED50 4 ng/ml and 1 ng/ml in 4 and 8 h, respectively), thus indicating that the toxin enters the cells to act. Bombesin and platelet-derived growth factor (PDGF) similarly decreased the ADP ribosylation of GRP78/BiP (ED50 0.5 nM and 2.5 ng/ml, respectively) but acted more rapidly than the toxin. Signaling pathways activated by the toxin, bombesin, and PDGF had effects on the ADP-ribosylation of GRP78/BiP. Thus, activation of protein kinase C alone by phorbol 12,13-dibutyrate was partially effective, and down-regulation of protein kinase C attenuated but did not block the action of the toxin, bombesin, and PDGF. Agents that mobilize Ca2+ from the endoplasmic reticulum (A23187, ionomycin, and thapsigargin) caused a decrease in the ADP ribosylation of GRP78/BiP that was similar in magnitude to that achieved by the toxin, bombesin, and PDGF, implicating a role for inositol 1,4,5-trisphosphate mediated Ca2+ mobilization in the action of the mitogenic agents. The growth factor-induced decrease in the ADP-ribosylation of GRP78/BiP may represent its conversion from an inactive to an active state. PMID- 1460025 TI - The role of the mature domain of proOmpA in the translocation ATPase reaction. AB - The export of proOmpA, the precursor of outer membrane protein A from Escherichia coli, requires preprotein translocase, which is comprised of SecA, SecY/E, and acidic phospholipids. Previous studies of proOmpA translocation intermediates (Schiebel, E., Driessen, A. J. M., Hartl, F.-U., and Wickner, W. (1991) Cell 64, 927-939) suggested that the "slippage" of the translocating polypeptide chain and the high level of ATP hydrolysis, characteristic of the "translocation ATPase," were part of a futile cycle. To examine the role of the mature domain of proOmpA in its translocation-dependent ATP hydrolysis, we used chemical cleavage to generate NH2-terminal fragments of this preprotein. Each fragment contained the 21-residue leader region and either 53 or 228 residues of the mature domain (preproteins P74 and P249, respectively). As observed with full-length proOmpA, the translocation of each fragment requires ATP and both the SecA and SecY/E domains of translocase and is stimulated by the transmembrane proton electrochemical gradient. The apparent maximal velocities of P74 and proOmpA translocation are similar. While the translocation of P74 and of proOmpA show the same apparent Km for ATP, far less ATP is hydrolyzed during the translocation of P74. Thus, the mature carboxyl-terminal domain of proOmpA has a major role in supporting the translocation ATPase. PMID- 1460026 TI - Distinct sterol and nonsterol signals for the regulated degradation of 3-hydroxy 3-methylglutaryl-CoA reductase. AB - The in vivo turnover rate of the endoplasmic reticulum protein 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the mevalonate (MVA) pathway, is accelerated when excess MVA or sterols are added to the growth medium of cells. As we have shown recently (Roitelman, J., Bar-Nun, S., Inoue, S., and Simoni, R. D. (1991) J. Biol. Chem. 266, 16085-16091), perturbation of cellular Ca2+ homeostasis abrogates the MVA-accelerated degradation of HMG-CoA reductase and HMGal. Here we show that, in contrast, the sterol-accelerated degradation of HMG-CoA reductase is unaffected by Ca2+ perturbation achieved either by Ca2+ ionophore or by inhibitors of the endoplasmic reticulum Ca(2+)-ATPase. The differential effects of Ca2+ perturbation can be attributed neither to global alteration in protein synthesis nor to inhibition of MVA conversion to sterols. Yet, such manipulations markedly reduce the incorporation of MVA into cellular macromolecules, including prenylated proteins. Furthermore, we directly demonstrate that MVA gives rise to at least two distinct signals, one that is essential to support the effect of sterols and another that operates independently of sterols. Our results indicate that the cellular signals operating in the MVA-accelerated turnover of HMG-CoA reductase are distinct from those involved in the sterol-regulated degradation. A working model for the degradation pathway is proposed. PMID- 1460027 TI - The primary structure of rat ribosomal protein S5. A ribosomal protein present in the rat genome in a single copy. AB - The amino acid sequence of the rat 40 S ribosomal subunit protein S5 was deduced from the sequence of nucleotides in a recombinant cDNA and confirmed by the determination, directly from the protein, of 17 residues near the NH2 terminus. S5 has 204 amino acids; the molecular weight is 22,863. The protein designated S5a has the same amino acid sequence as S5 except that it lacks the NH2-terminal 5 residues. It is not known whether the conversion of a portion of S5 to S5a is physiological or fortuitous. The mRNA for S5 has about 820 nucleotides. Hybridization of the S5 cDNA to digests of nuclear DNA indicates that the rat genome has only a single copy of the gene; this is in distinction to the mouse and human genomes which have three to six copies of the S5 gene. Rat ribosomal protein S5 is related to the eubacteria, the arachaebacteria, and the chloroplast family of S7 ribosomal proteins. There is a peptide of 16 residues at the carboxyl terminus of S5 that is highly conserved in 18 species spanning the three kingdoms and chloroplasts. PMID- 1460028 TI - A Saccharomyces cerevisiae DNA helicase associated with replication factor C. AB - A novel DNA helicase has been isolated from Saccharomyces cerevisiae. This DNA helicase co-purified with replication factor C (RF-C) during chromatography on S Sepharose, DEAE-silica gel high performance liquid chromatography (HPLC), Affi Gel Blue-agarose, heparin-agarose, single-stranded DNA-cellulose, fast protein liquid chromatography MonoS, and hydroxyapatite HPLC. Surprisingly, the helicase could be separated from RF-C by sedimentation on a glycerol gradient in the presence of 200 mM NaCl. The helicase is probably a homodimer of a 60-kDa polypeptide, which by UV cross-linking has been shown to bind ATP. It has a single-stranded DNA-dependent ATPase activity, with a Km for ATP of 60 microM. The DNA helicase activity depends on the hydrolysis of NTP (dNTP), with ATP and dATP the most efficient cofactors, followed by CTP and dCTP. The DNA helicase has a 5' to 3' directionality and is only marginally stimulated by coating the single stranded DNA with the yeast single-stranded DNA-binding protein RF-A. PMID- 1460029 TI - Brefeldin A induced inhibition of de novo globo- and neolacto-series glycolipid core chain biosynthesis in human cells. Evidence for an effect on beta 1- >4galactosyltransferase activity. AB - De novo synthesis of neolacto-series glycolipids has been studied in human cell lines via metabolic labeling of ceramide with [3H]serine. Intense labeling of ceramide mono- and dihexoside glycolipids occurred with labeling of progressively longer chain derivatives with increasing time. Most of the label was recovered in neutral glycolipids with about 5% of the total labeling in the ganglioside fraction. Experiments done using cell treatment with 2.5 micrograms/ml brefeldin A resulted in a stimulation in the total amount of labeling, accumulation of a neutral glycolipid identified as Lc3 due to inhibited transfer of the neolacto series core chain terminal beta-Gal residue, and a corresponding inhibition of labeling of longer chain neutral glycolipids in all cell lines. Brefeldin A also blocked synthesis of the globo-series precursor, Gb3, longer chain sialylated structures such as IV3NeuAcnLc4, but not de novo GM3 synthesis. Brefeldin A treatment had no effect on cellular beta 1-->3N-acetylglucosaminyl-, beta 1- >4galactosyl-, or alpha 1-->3fucosyltransferase specific activities, nor was it inhibitory in beta 1-->4galactosyltransferase assays in vitro. The results describe brefeldin A-induced blocks in globo- and neolacto-series glycolipid biosynthesis, consistent with differential localization of enzymes in intracellular membranes. In particular, the results suggest that the beta 1- >4galactosyltransferase in these cells is either not redistributed by brefeldin A or is otherwise rendered nonfunctional. PMID- 1460030 TI - Affected paroxysmal nocturnal hemoglobinuria T lymphocytes harbor a common defect in assembly of N-acetyl-D-glucosamine inositol phospholipid corresponding to that in class A Thy-1- murine lymphoma mutants. AB - Deficient expression of glycoinositol phospholipid (GPI) anchored proteins in affected paroxysmal nocturnal hemoglobinuria (PNH) cells has been traced to a defect in GPI anchor assembly. In a previous study (Schubert, J., Schmidt, R. E., and Medof, M. E. (1993) J. Biol. Chem., in press) we characterized the biosynthesis of putative Man-containing GPI anchor precursors in normal peripheral blood lymphocytes and investigated assembly of these intracellular GPI intermediates in CD48- affected and CD48+ unaffected T and natural killer cell lines of PNH patients. We found that affected T cells from five patients exhibited a uniform defect in which dolichol-phosphoryl-Man was synthesized but no GPI mannolipids were expressed. In this study, membranes of patients' affected T cells were labeled with UDP-[3H]GlcNAc to evaluate earlier steps in GPI synthesis, and intact cells were fused to Thy-1- murine lymphoma mutants harboring different defects in early GPI assembly to test for the presence of corresponding or complementary lesions. In all cases, affected cell membranes failed to assemble GlcNAc-inositol phospholipid, the initial precursor of GPI anchor structures, and the intact cells failed to complement class A mutants while complementing other classes. Affected polymorphonuclear leukocytes from three additional patients of different origin were then labeled with [3H]Man and the labeling patterns found to correspond to those obtained with the T lymphocytes. Taken together the data indicate that the genetic lesion in PNH cells resides in a DNA element which: 1) encodes a product required for the synthesis of GlcNAc-inositol phospholipid, 2) corresponds to that altered in class A Thy-1- murine lymphoma mutants, and 3) is commonly affected in different patients. PMID- 1460032 TI - Purification and characterization of the rat spermatid basic nuclear protein TP4. AB - Following elongation of spermatids in mammals, the histones are replaced by a set of basic nuclear transition proteins; in the rat there are four, named TP1-TP4. Of these, TP1 and TP2 are well characterized. Here we report the purification to homogeneity of TP4 from rat spermatids. It is a low molecular mass (about 13-20 kDa) basic protein with arginine and lysine constituting 24 mol % and histidine 2.2 mol %. Its 25 N-terminal amino acids were sequenced, and no sequence homologies with any known protein were found. Polyclonal antibodies raised against it in rabbit did not cross-react with other transition proteins, protamines, or histones. The presence of TP4 during sperm development was monitored by cell separation studies. No TP4 was detected in round spermatids, and along with TP1 and TP2, it is present in step 13-15 spermatids and its amount decreased in steps 16-19. Trace amounts of TP4 were also detected in epididymal sperm. A possible role for TP4 in spermatid and sperm chromatin structure is discussed. PMID- 1460033 TI - Differential regulation of biglycan and decorin by retinoic acid in bovine chondrocytes. AB - The small, leucine-rich proteoglycans, decorin and biglycan, are prominent components of many extracellular matrices and are differentially regulated in various tissues. We have examined the effects of retinoic acid (RA) on the expression of biglycan and decorin at the protein and mRNA levels in cultured bovine articular chondrocytes. Biglycan protein expression is rapidly turned off after 1-2 days of treatment with RA. In contrast, decorin protein expression is increased 12-18-fold following 3 days of RA treatment. The level of biglycan mRNA was also rapidly reduced upon RA treatment, mirroring the protein expression. The reduction was apparent by 6 h, and, by 4 days, the levels were nearly undetectable. In contrast, decorin mRNA was induced upon treatment with RA. The increase in decorin message levels was first apparent by 24 h, reaching maximum by 2 days, and remained constant through 4 days. The repression of biglycan mRNA displayed equal sensitivity to RA concentrations from 10(-5) to 10(-9) M. Decorin mRNA was induced in a dose-dependent fashion by RA. Retinoic acid at a concentration of 10(-5) M, the highest dose examined, resulted in maximal induction of the message, and control levels were obtained with 10(-8) M. The protein synthesis inhibitor cycloheximide inhibited the induction of decorin mRNA, indicating that the induction by RA was a secondary event. In contrast, the repression of biglycan by RA was not significantly altered by cycloheximide, showing that the repression was a direct effect. Actinomycin D inhibited the induction of decorin mRNA, indicating that transcription was required for the induction. Nuclear run-on assays confirmed that RA was regulating biglycan mRNA expression at the transcription level. A 24-h RA treatment decreased the level of transcription of the biglycan gene 5-fold. In contrast, no increase in transcription from the decorin gene could be detected by nuclear run-on assays. Therefore, the elevation in decorin mRNA levels observed after RA treatment was the result of a post-transcriptional event, most likely the consequence of stabilization of the message. This study demonstrates that the genes for these two similar proteoglycans are under very different forms of regulation by RA in chondrocytes. The pattern of differential expression of biglycan and decorin could serve as an additional marker for indicating changes of the cartilage phenotype. PMID- 1460031 TI - Probing the phosphocholine-binding site of human C-reactive protein by site directed mutagenesis. AB - Human C-reactive protein (CRP) can activate the classical pathway of complement and function as an opsonin only when it is complexed to an appropriate ligand. Most known CRP ligands bind to the phosphocholine (PCh)-binding site of the protein. In the present study, we used oligonucleotide-directed site-specific mutagenesis to investigate structural determinants of the PCh-binding site of CRP. Eight mutant recombinant (r) CRP, Y40F; E42Q; Y40F, E42Q; K57Q; R58G; K57Q, R58G; W67K; and K57Q, R58G, W67K were constructed and expressed in COS cells. Wild-type and all mutant rCRP except for the W67K mutants bound to solid-phase PCh-substituted bovine serum albumin (PCh-BSA) with similar apparent avidities. However, W67K rCRP had decreased avidity for PCh-BSA and the triple mutant, K57Q, R58G, W67K, failed to bind PCh-BSA. Inhibition experiments using PCh and dAMP as inhibitors indicated that both Lys-57 and Arg-58 contribute to PCh binding. They also indicated that Trp-67 provides interactions with the choline group. The Y40F and E42Q mutants were found to have increased avidity for fibronectin compared to wild-type rCRP. We conclude that the residues Lys-57, Arg-58, and Trp-67 contribute to the structure of the PCh-binding site of human CRP. Residues Tyr-40 and Glu-42 do not appear to participate in the formation of the PCh-binding site of CRP, however, they may be located in the vicinity of the fibronectin-binding site of CRP. PMID- 1460034 TI - Identification of an upstream regulatory region essential for cell type-specific transcription of the pro-alpha 2(V) collagen gene (COL5A2). AB - The transcriptional features of the human alpha 2(V) collagen gene (COL5A2) were examined by transfection experiments coupled to various DNA binding assays. This approach identified an upstream region essential for the cell type-specific expression of the COL5A2 promoter. Within this region are two nuclear factor binding sites, FP-A and FP-B, responsible for the formation of distinct DNA protein complexes. Mutations introduced across each of the two binding sites eliminated the formation of the cognate complex and decreased promoter activity by about 3-fold (FP-A) and 40-fold (FP-B) in transfection experiments. Competition experiments using recognition sequences for known transcription factors exhibiting some similarity to the FP-A- and FP-B-binding sites failed to inhibit COL5A2/protein interactions. Thus, COL5A2 expression appears to be under the positive control of a short regulatory sequence likely to harbor two novel nuclear factor-binding sites. PMID- 1460036 TI - Purification and characterization of a Fuc alpha 1-->2Gal beta 1--> and GalNAc beta 1-->-specific lectin in root tubers of Trichosanthes japonica. AB - A prominent lectin in the root tubers of Trichosanthes japonica was purified by affinity chromatography on a porcine stomach mucin-Sepharose column and termed TJA-II. The molecular mass of the native lectin was determined to be 64 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and TJA-II was separated into two different subunits of 33 and 29 kDa in the presence of 2 mercaptoethanol. The respective subunits contained mannose, N-acetylglucosamine, fucose, and xylose. It was determined by equilibrium dialysis to have two equal binding sites per molecule, the association constant toward tritium-labeled Fuc alpha 1-->2Gal beta 1-->3GlcNAc beta 1-->3Gal beta 1-->4GlcOT being K alpha = 3.05 x 10(5) M-1. The precise carbohydrate binding specificity of immobilized TJA II was studied using various tritium-labeled oligosaccharides. A series of oligosaccharides possessing Fuc alpha 1-->2Gal beta 1--> or GalNAc beta 1--> groups at their nonreducing terminals showed stronger binding ability than ones with Gal beta 1-->GlcNAc (Glc) groups, indicating that TJA-II fundamentally recognizes a beta-galactosyl residue and the binding strength increases on substitution of the hydroxyl group at the C-2 position with a fucosyl or acetylamino group. This lectin column is useful for fractionating oligosaccharides or glycoproteins containing blood group type 1H, type 2H, and Sd antigenic determinants. PMID- 1460035 TI - Cell-mediated cleavage of Pseudomonas exotoxin between Arg279 and Gly280 generates the enzymatically active fragment which translocates to the cytosol. AB - Pseudomonas exotoxin (PE) is a three-domain toxin which is cleaved by a cellular protease within cells and then reduced to generate two prominent fragments (Ogata, M., Chaudhary, V. K., Pastan, I., and FitzGerald, D. J. (1990) J. Biol. Chem. 265, 20678-20685). The N-terminal fragment is 28 kDa in size and contains the binding domain. The 37-kDa C-terminal fragment, which translocates to the cytosol, contains the translocation domain and the ADP-ribosylation domain. Cleavage followed by reduction is essential for toxicity since mutant forms of the toxin that cannot be cleaved by cells are nontoxic. Previous results with these mutants suggest that cleavage occurred in an arginine-rich (arginine residues are at positions 274, 276, and 279) disulfide loop near the beginning of the translocation domain, but the exact site of cleavage was not determined. Since very few molecules of the 37-kDa fragment are generated within cells it was not possible to determine the site of cleavage by performing a conventional N terminal sequence analysis of the 37-kDa fragment. Two experimental approaches were used to overcome this limitation. First, existing amino acids near the cleavage sites were replaced with methionine residues; this was followed by the addition of [35S]methionine-labeled versions of these toxins to cells. The pattern of radioactive toxin fragments recovered from the cells indicated that the toxin was cleaved either just before or just after Arg279. Second, [3H]leucine-labeled toxin was produced and added to the cells. Sequential Edman degradations were performed on the small amount of radioactive 37-kDa fragment that could be recovered from toxin-treated cells. A peak of radioactivity in the fifth fraction indicated that leucine was the 5th amino acid on the C-terminal side of the cleavage site. This result confirmed that cleavage was between Arg279 and Gly280. PMID- 1460037 TI - Interleukin 2-induced activation of Ras requires two domains of interleukin 2 receptor beta subunit, the essential region for growth stimulation and Lck binding domain. AB - Interleukin 2 (IL-2) can stimulate the proliferation of various kinds of T-cell lines. The receptor for IL-2 is composed of at least two subunits (alpha and beta), of which beta subunit plays the major role in transducing growth signals into the cells. A nonreceptor-type tyrosine kinase, Lck, is associated with IL-2 receptor beta subunit, and the binding of IL-2 to its receptor induces the activation of Lck. On the other hand, it has been shown that stimulation of T cells with IL-2 causes rapid activation of Ras protein. In this paper, we describe that both of the two regions in IL-2 receptor beta subunit, the indispensable region for the induction of cell growth (serine-rich region) and the binding region of Lck protein (acidic region), are required for the activation of Ras. These two regions are also required for tyrosine phosphorylation of an 85-kDa cellular protein (p85) and the accumulation of fos and jun mRNAs. This observation suggests also that the activation of a receptor associated tyrosine kinase in response to IL-2-stimulation is primarily responsible for subsequent activation of the pathway through Ras to Fos and Jun. PMID- 1460038 TI - The Na-K-Cl cotransport protein of shark rectal gland. I. Development of monoclonal antibodies, immunoaffinity purification, and partial biochemical characterization. AB - The Na-K-Cl cotransporter mediates the coupled transport of Na, K, and Cl across the plasma membrane of many animal cell membranes. It is inhibited by loop diuretics such as furosemide, bumetanide, and benzmetanide. We have developed a panel of monoclonal antibodies directed against the 195-kDa shark rectal gland Na K-Cl cotransport protein. Four representative antibodies (J3, J4, J7, and J25), each of which recognizes a discrete structural domain, were selected for detailed characterization. When a radiolabeled loop diuretic is bound to the cotransporter prior to solubilization, each antibody immunoprecipitates the same diuretic protein complex. Of the four antibodies, J4 favors the native protein over the denatured one and does not bind well to proteolytic fragments; in contrast, J7 recognizes the cotransporter only after it has been solubilized. J3, J7, and J25 each recognize a unique ensemble of proteolytic fragments of the 195-kDa protein; analysis of the patterns of recognition has yielded a tentative assignment of the approximate location of the epitopes within the peptide. When the cotransport protein is treated with N-glycanase to remove N-linked oligosaccharides, its apparent mass decreases to approximately 135 kDa. The deglycosylated form is recognized by each of the antibodies except J25; this suggests that the J25 epitope is within the oligosaccharide component or in a peptide domain whose folding is disturbed by carbohydrate removal. An immunoaffinity matrix constructed with the J4 antibody permits single-step purification of the 195-kDa protein; other proteins copurify with the large glycoprotein, but none of these appear to be subunits of a stoichiometric complex. The amino acid sequence of four fragments of the 195-kDa cotransport protein is reported. Immunofluorescence and immunoelectron microscopy demonstrates, in agreement with physiological evidence, that the 195-kDa protein is distributed along the basolateral membrane and excluded from the apical membrane of the rectal gland secretory cell. PMID- 1460039 TI - Beta gamma-subunit activation of G-protein-regulated phospholipase C. AB - The availability of purified G alpha 11 and the G-protein-regulated phospholipase C from turkey erythrocytes has allowed an examination of the direct effects of G protein beta gamma-subunit on the components of the inositol lipid signaling system. Reconstitution of purified turkey erythrocyte or bovine brain beta gamma subunit into phospholipid vesicles containing G alpha 11 inhibited AlF4- induced activation of phospholipase C. However, beta gamma-subunit at higher concentrations increased phospholipase C activity. This stimulatory effect of beta gamma-subunit on phospholipase C did not require the presence of the alpha subunit. G alpha o had no effect on the catalytic activity of phospholipase C. However, coreconstitution of G alpha o and beta gamma-subunit shifted to the right the concentration-effect curve for beta gamma-subunit-promoted activation of phospholipase C. As was observed with G alpha 11, the increase in activity observed in the presence of beta gamma-subunit occurred as an increase in the maximal activity and with no change in the apparent affinity for Ca2+ for phospholipase C activation. The concentration dependence of G alpha 11 for activation of turkey erythrocyte phospholipase C and bovine brain phospholipase C beta, as well as the concentration dependence of the two enzymes for activation by G alpha 11, were very similar. In contrast, beta gamma-subunit was a much less effective activator of bovine brain phospholipase C-beta than the turkey erythrocyte enzyme. The observation of direct effects of free beta gamma-subunit on phospholipase C extend the possibilities for receptor-mediated regulation of this signaling pathway. PMID- 1460040 TI - Mutational analysis of the adenovirus 2 IVa2 initiator and downstream elements. AB - The initiator element of the adenovirus type 2 IVa2 promoter is sufficient to direct accurate initiation by RNA polymerase II. Analysis of the effects of substitution of specific base pairs on initiator activity in in vitro transcription systems indicated that specific sequences between positions -4 and +5 were essential for initiator activity. Mutations that impaired or eliminated initiator activity altered both base pairs that are conserved in sequence-related initiators and nonconserved sequences. Neither the downstream TA-rich sequence of the IVa2 promoter, nor the adenovirus 2 major late TATA element placed at the same downstream site could overcome the severe inhibitory effects of initiator mutations, indicating that the initiator is the primary determinant of the specificity and direction of IVa2 transcription. By contrast, when the ML TATA element was placed 31 nucleotides upstream of the IVa2 initiator, the precise specificity, but neither the efficiency nor direction of transcription, depended on the presence of a functional initiator. Activity of the IVa2 promoter was relatively insensitive to changes in the orientation or nature of the TA-rich sequence. Furthermore, only a promoter containing the ML TA-TAAAA sequence downstream of the IVa2 initiator was competent to direct both IVa2 transcription and transcription from the opposite strand. The implications of this functional difference for recognition of the downstream element are discussed. PMID- 1460041 TI - High affinity ligand binding is not essential for granulocyte-macrophage colony stimulating factor receptor activation. AB - The high affinity receptor of the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) is a heterodimer composed of two members of the cytokine receptor superfamily. GM-CSF binds to the alpha-subunit (GM-R alpha) with low affinity and to the receptor alpha beta complex (GM-R alpha beta) with high affinity. The GM-CSF.GM-R alpha beta complex is responsible for biological activity. Interactions of the N-terminal helix of mouse GM-CSF with mGM-R alpha beta were examined by introducing single alanine substitutions of hydrophilic residues in this region of mGM-CSF. The consequences of these substitutions were evaluated by receptor binding and biological assays. Although all mutant proteins exhibited near wild-type biological activity, most were defective in high affinity receptor binding. In particular, substitution of Glu-21 with alanine abrogated high affinity binding leaving low affinity binding unaffected. Despite near wild-type biological activity, no detectable binding interaction of this mutant with mGM-R beta in the context of mGM-R alpha beta was observed. Cross linking studies showed an apparent interaction of this mutant protein with mGM-R alpha beta. The deficient receptor binding characteristics and near wild-type biological activity of this mutant protein demonstrate that mGM-CSF receptor activation can occur independently of high affinity binding, suggesting that conformational changes in the receptor induced by mGM-CSF binding generate an active ligand-receptor complex. PMID- 1460042 TI - Polypyrimidine tract binding protein interacts with sequences involved in alternative splicing of beta-tropomyosin pre-mRNA. AB - Previous studies of alternative splicing of the rat beta-tropomyosin gene have shown that nonmuscle cells contain factors that block the use of the skeletal muscle exon 7 (Guo, W., Mulligan, G. J., Wormsley, S., and Helfman, D. M. (1991) Genes & Dev. 5, 2095-2106). Using an RNA mobility-shift assay we have identified factors in HeLa cell nuclear extracts that specifically interact with sequences responsible for exon blockage. Here we present the purification to apparent homogeneity of a protein that exhibits these sequence specific RNA binding properties. This protein is identical to the polypyrimidine tract binding protein (PTB) which other studies have suggested is involved in the recognition and efficient use of 3'-splice sites. PTB binds to two distinct functional elements within intron 6 of the beta-tropomyosin pre-mRNA: 1) the polypyrimidine tract sequences required for the use of branch points associated with the splicing of exon 7, and 2) the intron regulatory element that is involved in the repression of exon 7. Our results demonstrate that the sequence requirements for PTB binding are different than previously reported and shows that PTB binding cannot be predicted solely on the basis of pyrimidine content. In addition, PTB fails to bind stably to sequences within intron 5 and intron 7 of beta-TM pre-mRNA, yet forms a stable complex with sequences in intron 6, which is not normally spliced in HeLa cells in vitro and in vivo. The nature of the interactions of PTB within this regulated intron reveals several new details about the binding specificity of PTB and suggests that PTB does not function exclusively in a positive manner in the recognition and use of 3'-splice sites. PMID- 1460043 TI - Genomic organization of the mouse granzyme A gene. Two mRNAs encode the same mature granzyme A with different leader peptides. AB - Granzyme A is a serine protease that, together with the other granular components of cytotoxic T lymphocyte (CTL) cells, has been implicated in the cytolysis process. We report here two different messages and the genomic organization of the mouse granzyme A gene. The granzyme A gene is composed of six exons spanning 7 kilobases. Alternative splicing of the second exon results in the two transcripts. The two mRNA species encode the same mature granzyme A protein but with different leader sequences. The first (HF1) encodes a typical leader signal sequence similar to other granzymes, but the second (HF2) putative leader sequence is different and less hydrophobic. Both messages are present in cultured CTL cell lines and in normal lymphoid tissues. They are both induced when CTL cells are activated in vitro or in vivo. Both messages can be translated in vitro, although the HF1 message appears to be much more efficient as a template. The putative 5' promoter region of the HF gene sequenced (500 base pairs of upstream sequences) contains no well defined promoter sequences aside from the TATA box. The results suggest that (a) granzyme A may be produced with putative different leader sequences from two different mRNAs; (b) this may provide a model system for studying alternate splicing and the evolution of a complex enzymatic system in an organelle; and (c) the genomic DNA reported will be useful for studying transcription regulations involved in controlling the specific expression pattern of this gene. PMID- 1460044 TI - Impact of O-glycosylation on the function of human intestinal lactase-phlorizin hydrolase. Characterization of glycoforms varying in enzyme activity and localization of O-glycoside addition. AB - Lactase-phlorizin hydrolase (LPH) is an integral intestinal brush border membrane glycoprotein responsible for the hydrolysis of lactose, the primary carbohydrate in mammalian milk. To assess the role of N- and O-glycosylation on the function of LPH, lectin-binding experiments combined with enzymatic and chemical deglycosylation of purified LPH molecules were performed. These investigations provided evidence for the existence of two forms of brush border LPH, an N glycosylated molecule (LPHN) and an N- and O-glycosylated molecule (LPHN/O). These two forms could be discriminated on the basis of (i) their binding capacity to Helix pomatia lectin, which has high specificity toward O-linked oligosaccharides, and (ii) their deglycosylation patterns with endo-beta-N acetylglucosaminidase F/GF, O-glycanase, and trifluoromethanesulfonic acid. Interestingly, both forms have identical Km values (approximately 14 mM) when assayed with lactose, but hydrolyze this substrate at different rates. Thus, the N- and O-glycosylated form exhibits almost a 4-fold higher Vmax than that of the N-glycosylated enzyme (3.28 nM/min versus 0.90 nM/min) and is therefore enzymatically more active than the latter. Sequential affinity chromatography of glycopeptides derived from [3H]mannose-labeled LPHN and LPHN/O on lectin columns revealed similar patterns of N-linked glycosylation of both forms indicating that the presence of O-linked oligosaccharides did not affect or alter the processing of N-linked oligosaccharides. O-Linked glycosylation of LPH appears to occur in the Golgi apparatus, since the earliest detectable forms of LPH, the mannose-rich precursor (pro-LPH) is not O-glycosylated. In view of the fact that differentiation of intestinal crypt cells to mature epithelial cells is accompanied by significant phenotypical, morphological, and structural alterations, including changes in the levels of several Golgi glycosyl, -sialyl, galactosyl-, and N-acetylgalactosaminyltransferases, and since O-glycosylation is a Golgi event, we suggest that the generation of LPHN and LPHN/O is strongly linked to differentiation of intestinal cells. Finally, the variations in the enzymatic activity of the two forms propose a role for O-glycosylation in posttranslational regulation of LPH activity. PMID- 1460045 TI - Cloning, sequencing, and expression of the fadD gene of Escherichia coli encoding acyl coenzyme A synthetase. AB - In the enteric bacterium, Escherichia coli, acyl coenzyme A synthetase (fatty acid:CoA ligase (AMP-forming) EC 6.2.1.3) activates exogenous long-chain fatty acids concomitant with their transport across the inner membrane into metabolically active CoA thioesters. These compounds serve as substrates for acyl CoA dehydrogenase in the first step in the process of beta-oxidation. The acyl CoA synthetase structural gene, fadD, has been identified on clone 6D1 of the Kohara E. coli gene library and by a process of subcloning and complementation analyses shown to be contained on a 2.2-kilobase NcoI-ClaI fragment of genomic DNA. The polypeptide encoded within this DNA fragment was identified following T7 RNA polymerase-dependent induction and estimated to be M(r) = 62,000 using SDS polyacrylamide gel electrophoresis. The N-terminal amino acid sequence of acyl CoA synthetase was determined by automated sequencing to be Met-Lys-Lys-Val-Trp Leu-Asn-Arg-Tyr-Pro. Sequence analysis of the 2.2-kilobase NcoI-ClaI fragment revealed a single open reading frame encoding these amino acids as the first 10 residues of a protein with a molecular weight of 62,028. The initiation codon for methionine was TTG. Primer extension of total in vivo mRNA from two fadD-specific oligonucleotides defined the transcriptional start at an adenine residue 60 base pairs upstream from the predicted translational start site. Two FadR operator sites of the fadD gene were identified at positions -13 to -29 (OD1) and positions -99 to -115 (OD2) by DNase I footprinting. Comparisons of the predicted amino acid sequence of the E. coli acyl-CoA synthetase to the deduced amino acid sequences of the rat and yeast acyl-CoA synthetases and the firefly luciferase demonstrated that these enzymes shared a significant degree of similarity. Based on the similar reaction mechanisms of these four enzymes, this similarity may define a region required for the same function. PMID- 1460046 TI - Type I procollagens containing substitutions of aspartate, arginine, and cysteine for glycine in the pro alpha 1 (I) chain are cleaved slowly by N-proteinase, but only the cysteine substitution introduces a kink in the molecule. AB - Type I procollagen was purified from the medium of dermal fibroblasts cultured from four individuals with osteogenesis imperfecta (OI) type II who had mutations in the COL1A1 gene of type I procollagen. The procollagens were mixtures of normal molecules and molecules that contained substitutions of aspartate for glycine 97, arginine for glycine 550, cysteine for glycine 718, and aspartate for glycine 883 in one or both of the alpha 1 (I) chains of the molecule. The procollagens were cleaved more slowly than control type I procollagen by procollagen N-proteinase. Double-reciprocal plots of initial relative velocities and initial substrate concentrations indicated that the OI procollagens were all cleaved slowly by N-proteinase because of decreased Vmax, rather than increased Km. This suggested that slow cleavage of the OI procollagens by N-proteinase was the result of slow conversion of the N-proteinase-procollagen complex. Further experiments showed that the vertebrate collagenase A fragment of the aspartate for glycine alpha 1(I) 883 OI procollagen that contained the N-proteinase cleavage site but not the site of the substitution was also cleaved more slowly by N-proteinase than the normal vertebrate collagenase A fragments in the samples. These data show, for the first time, that an altered triple-helical structure is propagated from the site of a substitution of a bulky residue for glycine to the amino-terminal end of the procollagen molecule and disrupts the conformation of the N-proteinase cleavage site. Rotary shadowing electron microscopy of molecules in the preparation of cysteine for glycine alpha 1(I)-718 showed the presence of a kink in approximately 5% of a population of molecules in which 60% were abnormal and 20% contained a disulfide bond. In contrast, procollagens containing aspartate and arginine for glycine were indistinguishable by rotary shadowing electron microscopy from those in control samples. The results here confirm previous suggestions that substitution of cysteine for glycine in the alpha 1(I) chain of type I collagen can introduce a kink near the site of the substitution. However, the presence of a kink is not a prerequisite for delayed cleavage of abnormal procollagens by N-proteinase. PMID- 1460047 TI - A tripeptide deletion in the triple-helical domain of the pro alpha 1(I) chain of type I procollagen in a patient with lethal osteogenesis imperfecta does not alter cleavage of the molecule by N-proteinase. AB - Dermal fibroblasts from a fetus with perinatal lethal osteogenesis imperfecta synthesized normal and abnormal type I procollagen molecules. The abnormal molecules contained one or two pro alpha 1(I) chains in which glycine, alanine, and hydroxyproline at positions 874, 875, and 876 in the triple-helical region were deleted as the result of a 9-base pair genomic deletion. Molecules that contained abnormal chains were overmodified from the site of the deletion toward the amino-terminal region of the molecule. Secretion of the overmodified molecules was impaired. The thermal stability of molecules containing abnormal chains was lower than that of normally modified molecules. After cleavage of molecules with vertebrate collagenase, the temperature of thermal denaturation of the overmodified A fragments was greater than that of the fragments from the normal molecules. The rates of cleavage of the normal and the abnormal molecules by N-proteinase were indistinguishable. Our findings suggest that the tripeptide deletion introduces a shift in the phase of the chains in the triple helix. This structural change is propagated from the site of the deletion toward the amino terminus of the molecule, but the subsequent alteration in the structure of the N proteinase cleavage site is not sufficient to cause a decrease in the rate of cleavage by the enzyme. PMID- 1460048 TI - Positive regulation of the skeletal alpha-actin gene by Fos and Jun in cardiac myocytes. AB - Transcription of the skeletal alpha-actin gene is selectively activated in rat myocardiocytes undergoing hypertrophy both in vivo and in vitro. In most of these models, transient expression of certain proto-oncogene transcription factors precedes hypertrophy and sarcomeric gene induction. Using expression vectors encoding Fos and Jun, the main constituents of transcriptional activator protein AP-1, we analyzed the role of these oncoproteins in mediating the transcriptional induction of skeletal alpha-actin by adrenergic stimulation. Both c-fos and c-jun were induced early after beta-adrenergic stimulation, with peak mRNA levels preceding skeletal alpha-actin induction by several hours. A second peak of c-jun mRNA coincided with skeletal alpha-actin induction. Co-transfection assays in cardiac myocytes and P19 teratocarcinoma cells demonstrated that over-expression of c-jun, or c-fos plus c-jun, transactivated the skeletal alpha-actin promoter by about 5-fold. Comparable activation was not seen for alpha-myosin heavy chain or cardiac alpha-actin promoters. Skeletal alpha-actin promoter sequences between -153 and -36 were required for maximal transactivation by c-fos/c-jun, and purified Fos and Jun were bound specifically within this region. A direct physiological role is suggested for the AP-1 transcription factor complex in regulating skeletal alpha-actin gene expression and alpha-actin isoform switching during the onset of signal-mediated cardiac myocyte hypertrophy. PMID- 1460049 TI - Characterization of components of the anaerobic ribonucleotide reductase system from Escherichia coli. AB - Anaerobic growth of Escherichia coli induces an oxygen-sensitive ribonucleoside triphosphate reductase system, different from the aerobic ribonucleoside diphosphate reductase (EC 1.17.4.1) of aerobic E. coli and higher organisms (Fontecave, M., Eliasson, R., and Reichard, P. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 2147-2151). We have now purified and characterized two proteins from the anaerobic system, provisionally named dA1 and dA3. dA3 is the actual ribonucleoside triphosphate reductase; dA1 has an auxiliary function. From gel filtration, dA1 and dA3 have apparent molecular masses of 27 and 145 kDa, respectively. In denaturing gel electrophoresis, dA3 gives two bands of closely related polypeptides with apparent molecular masses of 77 (beta 1) and 74 (beta 2) kDa. Immunological and structural evidence suggests that beta 2 is a degradation product of beta 1 and that the active enzyme is a dimer of beta 1. dA1 activity coincides on denaturing gels with a band of 29 kDa and thus appears to be a monomer. The reaction requires, in addition, an extract from E. coli heated for 30 min at 100 degrees C. Potassium is one required component, but one or several others remain unidentified and are provisionally designated fraction RT. With dA3, dA1, RT, and potassium ions, CTP reduction shows absolute requirements for S-adenosylmethionine, NADPH (with NADH as a less active substitute), dithiothreitol, and magnesium ions, and is strongly stimulated by ATP, probably acting as an allosteric effector. Micromolar concentrations of several chelators inhibit CTP reduction completely, suggesting the involvement of (a) transition metal(s). PMID- 1460050 TI - Activation of the anaerobic ribonucleotide reductase from Escherichia coli by S adenosylmethionine. AB - The anaerobic ribonucleoside triphosphate reductase from Escherichia coli reduces CTP to dCTP in the presence of a second protein, named dA1, and a Chelex-treated boiled extract of the bacteria, named RT. The reaction requires S adenosylmethionine, NADPH, dithiothreitol, ATP, and Mg2+ and K+ ions. It occurs only under anaerobic conditions. We now show that the overall reaction occurs in two steps. The first is an activation of the reductase by dA1 and RT and requires S-adenosylmethionine, NADPH, dithiothreitol, and possibly K+ ions. In the second step, the activated reductase reduces CTP to dCTP with ATP acting as an allosteric effector. During activation, S-adenosylmethionine is cleaved reductively to methionine + 5'-deoxyadenosine. This step is inhibited strongly by S-adenosylhomocysteine and various chelators. The activation of the anaerobic reductase shows a considerable similarity to that of pyruvate formate-lyase (Knappe, J., Neugebauer, F. A., Blaschkowski, H. P., and Ganzler, M. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1332-1335). PMID- 1460051 TI - The structure of the zinc sites of Escherichia coli DNA-dependent RNA polymerase. AB - X-ray absorption spectroscopy is ideally suited for the investigation of the electronic structure and the local environment (approximately 5 A) of specific atoms in biomolecules. While the edge region provides information about the valence state of the absorbing atom, the chemical identity of neighboring atoms, and the coordination geometry, the extended x-ray absorption fine structure region contains information about the number and average distance of neighboring atoms and their relative disorder. The development of sensitive detection methods has allowed studies using near physiological concentrations (as low as approximately 100 microM). RNA polymerase from Escherichia coli contains two zinc atoms: one tightly bound in the beta' subunit, the subunit that participates in template binding, and the other loosely bound in the beta subunit, the subunit that participates in substrate binding. X-ray absorption studies of these zinc sites in the native protein and of the zinc site in the beta' subunit after removal of the zinc in the beta subunit site by p (hydroxymercuri)benzenesulfonate (Giedroc, D. P., and Coleman, J. E. (1986) Biochemistry 25, 4969-4978) indicate that both zinc sites have octahedral coordination. The zinc in the beta' subunit site has four sulfur ligands at an average distance of 2.36 +/- 0.02 A and two oxygen (or nitrogen) ligands at an average distance of 2.23 +/- 0.02 A. The beta subunit zinc site has five sulfur ligands at an average distance of 2.38 +/- 0.01 A and one histidine nitrogen ligand at 2.14 +/- 0.02 A. These results are in general agreement with earlier biochemical and spectroscopic studies. PMID- 1460052 TI - In situ imaging of agonist-sensitive calcium pools in AR4-2J pancreatoma cells. Evidence for an agonist- and inositol 1,4,5-trisphosphate-sensitive calcium pool in or closely associated with the nuclear envelope. AB - The activation of phospholipase C by hormones and neurotransmitters activates a complex combination of Ca2+ release and accumulation by intracellular organelles. Previously, we demonstrated that, in some cell types, the fluorescent Ca2+ indicator, fura-2, can be loaded into intracellular, agonist-sensitive Ca2+ pools (Glennon, M. C., Bird, G. St. J., Kwan, C.-Y., and Putney, J. W., Jr. (1992) J. Biol. Chem. 267, 8230-8233). In the current study, we have attempted to exploit this phenomenon by employing digital fluorescence imaging of compartmentalized fura-2 to investigate the localization and function of the major intracellular sites of Ca2+ regulation in AR4-2J pancreatoma cells. By judicious use of a surface receptor agonist together with the Ca(2+)-ATPase inhibitor, thapsigargin, cellular regions were identified whose behavior indicates that they contain the sites of agonist- and inositol 1,4,5-trisphosphate-mediated intracellular Ca2+ release. These regions were located throughout the cell and may include the nuclear envelope. They were distinct in locus and behavior from two other regions, which counterstained with fluorescent markers for nuclei and mitochondria. Fura-2 in mitochondrial regions reported low resting levels of [Ca2+], and revealed that organelles in these regions accumulate and retain Ca2+ after agonist activation. These findings demonstrate that fluorescent Ca2+ indicators can be employed to directly monitor changes in [Ca2+] in the major Ca(2+)-regulating organelles, and provide the first in situ visualization and localization of the major sites of Ca2+ regulation in cells. PMID- 1460053 TI - Protein LG: a hybrid molecule with unique immunoglobulin binding properties. AB - Immunoglobulin (Ig)-binding bacterial proteins have attracted theoretical interest for their role in molecular host-parasite interactions, and they are widely used as tools in immunology, biochemistry, medicine, and biotechnology. Protein L of the anaerobic bacterial species Peptostreptococcus magnus binds Ig light chains, whereas streptococcal protein G has affinity for the constant (Fc) region of IgG. In this report, Ig binding parts of protein L and protein G were combined to form a hybrid molecule, protein LG, which was found to bind a large majority of intact human Igs as well as Fc and Fab fragments, and Ig light chains. Binding to Ig was specific, and the affinity constants of the reactions between protein LG and human IgG, IgGFc fragments, and kappa light chains, determined by Scatchard plots, were 5.9 x 10(9), 2.2 x 10(9), and 2.0 x 10(9) M 1, respectively. The binding properties of protein LG were more complete as compared with previously described Ig-binding proteins when also tested against mouse and rat Igs. This hybrid protein thus represents a powerful tool for the binding, detection, and purification of antibodies and antibody fragments. PMID- 1460054 TI - Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes. AB - The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3 gamma. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes. PMID- 1460055 TI - DNA binds and activates complement via residues 14-26 of the human C1q A chain. AB - The mechanism by which DNA activates the classical complement pathway was investigated, with emphasis upon the C1q binding sites involved. DNA bound to both the collagen-like and globular regions of C1q. Binding reactivity with DNA was retained after reduction/alkylation and sodium dodecyl sulfate treatment of C1q. DNA bound preferentially to the A chain of C1q. Binding sites for DNA were localized by using synthetic C1q A chain peptides to two cationic regions within residues 14-26 and 76-92, respectively. Peptides 14-26 and 76-92 avidly bound DNA in enzyme-linked immunosorbent and gel shift assays. Peptide 14-26 also precipitated with DNA and blocked its ability to bind C1q and activate C. Replacement of the two prolines with alanines or scrambling the order of the amino acids resulted in loss of ability of peptide 14-26 to inhibit C1q binding and complement activation by DNA; similar investigations showed a sequence specificity for peptide 76-92 as well. These experiments identify C1q A chain residues 14-26 as the major site, and residues 76-92 as a secondary site, through which DNA binds C1q and activates the classical complement pathway, and demonstrate that a peptide identical to residues 14-26 can modulate C1q binding and complement activation by DNA. PMID- 1460056 TI - Sequence and transcriptional analysis of the Escherichia coli rnt gene encoding RNase T. AB - The Escherichia coli rnt gene encoding the enzyme RNase T, which is responsible for the end-turnover of tRNA, was cloned on a 1.5-kilobase DNA fragment. When placed in pUC18 and pUC19 vectors this fragment led to approximately a 40-fold overexpression of RNase T activity. The cloned fragment was sequenced and was found to contain an open reading frame sufficient to encode a protein of 215 amino acids with a molecular weight of 23,521, which is close to the subunit molecular weight of RNase T; the fragment also contains a second incomplete open reading frame with some sequence similarity to RNA helicases. The derived sequence of RNase T showed no similarity to any of the other E. coli exoribonucleases sequenced to date. Primer extension analysis and deletion of part of the upstream region were used to identify the transcription start point and the promoter of the rnt gene. Northern and primer extension analysis revealed that the rnt message also included the second open reading frame, suggesting that rnt is part of an operon. PMID- 1460058 TI - Molecular cloning and sequencing of cDNA encoding the phosphatidylinositol kinase from rat brain. PMID- 1460057 TI - Functional analysis of the human platelet-derived growth factor A-chain promoter region. AB - The platelet-derived growth factor (PDGF) A-chain gene is a developmentally regulated gene that is expressed in high levels in a limited number of normal and transformed cell lines and in cells stimulated by cytokines, including PDGF itself. We have now analyzed potential regulatory elements in 3.6 kilobase pairs (kb) of the 5'-flanking sequences of the human PDGF A-chain gene using reporter gene constructs and transient transfection analyses. The region between base pairs (bp) -618 and +392 (relative to the transcription initiation site) is sufficient for optimal promoter activity. A highly G + C region containing three contiguous Sp1 binding sites between bp -150 and -33 contributes over 80% of promotor activity. DNase I footprinting analyses indicates that Sp1 binds to and protects over 57 bp of this G + C region. A functional serum response element is located within bp -477 and -468 and positively regulates induction of PDGF A by PDGF. A negative regulatory (silencer) element is located from -1.9 to -0.9 kb. The results suggest that the major constitutive expression of the PDGF A-chain gene requires a highly G + C-rich region containing three Sp1 binding sites and that induction of the PDGF A-chain gene by PDGF is mediated by a SRE located at bp -477 to -468. PMID- 1460059 TI - Wrist anatomy. AB - The multiple joints within the wrist form a complex structure capable of transmitting significant loads to the upper extremity while providing a mobile base for the precision movements of the hand. This duality is accomplished through a fine interplay between the carpal bones and an arrangement of highly specific ligamentous structures, a system loaded by balanced muscle forces. PMID- 1460060 TI - Ligamentous injuries to the wrist. Imaging techniques. AB - The variety of imaging techniques available to the clinician facilitates the diagnosis of acute and chronic wrist disorders. In most cases, conventional radiographs provide sufficient information. Computed and trispiral tomography, arthrography, video-fluoroscopy, and magnetic resonance imaging are additional imaging techniques that are useful in making the correct diagnosis and deciding on a course of treatment. PMID- 1460061 TI - Wrist arthroscopy. AB - Wrist arthroscopy has become a routine method of evaluating and treating wrist disorders. Technical advances and improved techniques have resulted in therapeutic modalities with a much lower morbidity rate. Specific indications for wrist arthroscopy are described, as well as techniques and precautions. PMID- 1460062 TI - The distal radioulnar joint. AB - A phylogenic review shows the DRUJ to be a highly evolved and specialized structure. The diarthrodial joint, in combination with the TFCC, ligament complex, and oblique fibers of the distal interosseous membrane, permit rotation while preserving stability and transmitting the load borne by the radiocarpal joint to both bones of the forearm. Our improved, yet imperfect, understanding of the anatomy, biomechanics, and pathophysiology of the region, abetted by new imaging modalities and wrist arthroscopy, permit more precise diagnosis and thus more rational treatment. The persistent inconsistency of our results belies our imperfect comprehension. Thus humbled, consider Goethe's admonition as a call to further scrutiny and investigation, "Theory and experience are opposed to each other in constant conflict. Only action can reconcile them." PMID- 1460063 TI - Treatment of scapholunate dissociation. Rotatory subluxation of the scaphoid. AB - The treatment of scapholunate dissociation remains controversial. Although good to excellent results have been reported using a variety of surgical techniques, they have often not been confirmed by other authors. Limited wrist mobility and the likelihood that degenerative changes will progress appear to be inherent in most approaches. The ideal treatment is to restore the normal anatomy and, with it, the function of the wrist. Destroying a normal joint by even a limited fusion as a means to provide stability to an abnormal joint is counter to our usual approach to disease. It is for that reason that more reliable soft-tissue reconstructive procedures are necessary. Those interested in arthroscopy are pursuing endoscopic methods of repair, but, at present, little progress is apparent. The physician who solves this problem with an uncomplicated and reliable surgical solution will have indebted us all. PMID- 1460064 TI - Lunate-triquetral and midcarpal joint instability. AB - Instability of the ulnar side of carpus centers around the triquetrum, which is suspended by the ulnar triquetral ligaments and supported proximally by the TFCC. The triquetrum guides the lunate by an interosseous membrane and stout palmar ligaments that provide a relatively rigid connection between the two bones. Disruption of the LT ligament is frequently associated with pathology in the ulnar carpal area and may progress to triquetral instability, VISI, and finally, degenerative arthritic changes on the ulnar side of the carpus. The diagnosis of LT injuries is made by stress radiographs, arthrography, video-fluoroscopy, and arthroscopy. Treatment is initially nonoperative, but if symptoms persist, surgery is warranted. Arthroscopic debridement and pinning the LT joint, ligament repair or reconstruction, and intercarpal arthrodesis have all been reported as successful treatments. For the chronic problem confined to the LT joint, a limited intercarpal arthrodesis of the joint is the most predictable procedure for relieving pain without causing any significant restrictions in wrist motions. When there is a dissociation pattern in addition to LT instability, a more extensive intercarpal arthrodesis is required. Midcarpal instability occurs at the triquetral-hamate joint and is characterized by a dynamic subluxation of the joint. During ulnar deviation, the joint undergoes an exaggerated shift from volar flexion to dorsiflexion. Supportive care is generally successful; although in chronic cases, a midcarpal joint arthrodesis is often required. PMID- 1460065 TI - Rehabilitation techniques for ligament injuries of the wrist. AB - The goal of treatment after any wrist injury is a pain-free, stable joint with sufficient strength and mobility to carry out the daily recreational, and occupational tasks required by the individual. Treatment varies considerably depending on the age of the patient, the severity of the initial injury, the operative procedure performed, and the specific guidelines requested by the referring physician. PMID- 1460066 TI - Anatomy of the joints of the thumb. AB - The three joints of the thumb differ markedly with respect to anatomy and function. Each contributes its own anatomic personality, and when functioning together, they allow the thumb to move with remarkable versatility and grace yet with the stability necessary to perform a wide variety of tasks. The carpometacarpal and interphalangeal joints allow for thumb mobility while the metacarpophalangeal joint provides stability. Thumb rotation primarily takes place at the CMC joint, although the MP and IP joints each contribute a small amount of pronation with flexion. Although much is known about the static structural anatomy of the thumb, its dynamic anatomy requires further investigation. The fluid, elegant and powerful movements of the thumb are complex, and defining the contributions of the various individual structures is difficult. Hopefully, future investigators using newer techniques will unravel the complexities of the functional anatomy of this remarkable digit. PMID- 1460067 TI - Anatomy of the joints of the fingers. AB - The anatomy and function of the three joints within each finger are mutually complementary; none functions independently of the other two. A complex, yet precise, intrinsic and extrinsic soft-tissue support links these three joints and provides a precisely articulated balance for the mobility of the finger. This complex interrelationship requires both strength and stability, which are inherent in the design of the bony architecture and their surrounding soft tissues. Understanding this interrelationship is essential for the accurate diagnosis and treatment of the numerous problems with which these joints are sometimes afflicted. PMID- 1460068 TI - Trapeziometacarpal joint injuries. AB - This article begins with discussions of anatomy and thumb movement. Palmar (anterior) ligament reconstruction is then discussed. Peritrapezial arthritis is also discussed. PMID- 1460069 TI - Metacarpophalangeal joint injuries of the thumb. AB - Dorsal capsular injuries, volar plate injuries, ulnar collateral ligament injuries, and radial collateral ligament injuries are all discussed in this article. Treatment is both discussed and illustrated for ease of comprehension. PMID- 1460070 TI - Carpometacarpal joint injuries of the fingers. AB - Injuries to the carpometacarpal joints are uncommon and are sometimes overlooked on initial radiographs. Their recognition depends on a careful physical and radiographic examination that may require trispiral tomograms and CT scans. Most injuries can be treated successfully by closed reduction and percutaneous fixation of the joint(s) using Kirschner wires. Chronic joint injuries can also be effectively treated, and if surgery is required, an arthrodesis will restore stability and eliminate discomfort. PMID- 1460071 TI - Metacarpophalangeal joint injuries in fingers. AB - Although uncommon, injuries to the MP joints of fingers must not be ignored. A loss of function in even a single MP joint can seriously impair overall hand function. The potential dire consequences of these injuries can be avoided by an accurate diagnosis at the time of injury and the institution of appropriate treatment. PMID- 1460072 TI - Capsular injuries of the proximal interphalangeal joint. AB - Although capsular injuries of the PIP joints are common, their management is frequently complicated. Successful treatment must begin with a detailed history because reviewing the mechanism of injury may provide information relevant to the pathomechanics of the capsular disruption and facilitate making an accurate diagnosis. Grades I and II volar plate and collateral ligament sprains represent the vast majority of PIP joint injuries. They are best treated with a short period of dorsal splinting followed by supervised mobilization. Although splinting is also applicable for grade II sprains associated with instability and most grade III sprains, the initial period of immobilization should be longer. The prognosis for recovery is generally good, although some residual tenderness or joint stiffness are common complications. Dorsal capsular injuries, if unrecognized, result in deformity rather than instability. The majority of these injuries can also be treated by closed means, but they require more prolonged immobilization and more commonly result in reduced mobility than volar plate and collateral ligament injuries. Capsular injuries that are compound, irreducible, or associated with a large intraarticular fracture can result in serious problems. Frequently, these injuries require primary surgical treatment, particularly in the case of the irreducible dislocation, which always requires surgery. An exception to the generally poor prognosis of these injuries is the irreducible volar dislocation because the central tendon remains intact permitting early postoperative joint mobilization. A chronic dislocation or late instability are fortunately not common sequela of capsular injuries; however, when they do occur, surgery is required. PMID- 1460073 TI - Distal joint injuries of the thumb and fingers. AB - The DIP joints of fingers and the interphalangeal joints of thumbs provide important stability and contribute to the flexion and extension arc of the digit. A variety of injuries can affect these joints, involving their ligaments, bones, and tendons. Instituting proper and effective treatment is predicated on making an accurate diagnosis of the injury and understanding the function of each anatomic structure. PMID- 1460074 TI - Contractures of the proximal interphalangeal joint. AB - Posttraumatic stiffness of proximal interphalangeal joints remains a difficult problem that severely compromises hand function. The emphasis of treatment must be on preventing the problem from developing, which begins within hours of the injury. Effective treatment involves a careful evaluation of the injury and then instituting a rational course of therapy. When surgery is necessary, the operative technique must be precise, and it requires a thorough understanding of the anatomic and pathomechanical factors that cause the contracture. Effective postoperative therapy and rehabilitation are integral parts of any surgical procedure, and they usually continue for many months. PMID- 1460075 TI - The boutonniere deformity. AB - Understanding the pathophysiology of the boutonniere deformity requires a complete understanding of the anatomy of the dorsal tendon apparatus. This unique tendon mechanism often becomes unbalanced, requiring correction of its components. Splinting is the cornerstone of treatment for the boutonniere deformity. In the acute stage, splinting ensures that the continuity of the central tendon to its insertion into the middle phalanx is maintained, and in the chronic stage, its function is to correct the flexion contracture of the PIP joint and stretch the retinacular ligaments. Splinting is also important postoperatively because it permits healing of the central tendon and lateral bands in their correct anatomic positions. Without proper splinting, the patient with the boutonniere deformity could not be successfully treated. Frequently, surgery is necessary, and the choice of procedure depends on the stage of the condition and the extent of the defect in the extensor tendon mechanism. The procedure also depends on the success of the splinting program and stretching of the tight retinacular structures. If passive joint mobility can be restored and if tendon imbalance and retinacular tightness persist, rebalancing is necessary. This rebalancing can be accomplished by a tenotomy of the terminal extensor tendon, a lysis or release of the retinacular structures, or release of the insertion of the extensor tendon at the base of the proximal phalanx. Reconstituting the defect in the central tendon over the PIP joint is accomplished by using a variety of procedures, including mobilization and advancement of the more proximal portion of the central tendon, shifting the lateral bands, or a tendon graft. PMID- 1460076 TI - Rehabilitation techniques for ligament injuries of the hand. AB - The contributions of the hand therapist to the treatment of ligament injuries in the hand requires a combination of skills. A thorough knowledge of the pathomechanics of these injuries is a necessary prerequisite in the initial evaluation and treatment planning stage. Focus should never be entirely on the injury; it is also important to understand the emotional effect that the injury has had on the patient's work and leisure activities. Therapy programs usually require edema control and reduction and a variety of static and dynamic splints. The ultimate goal is returning the patient to fully functional activities. PMID- 1460077 TI - High-performance liquid chromatographic separation of purine deoxyribonucleoside monophosphate-benzo[a]pyrene adducts. AB - Chromatographic methods that allow the separation of adducts of purine nucleoside 3'-phosphates with the pure enantiomers of the anti-dihydrodiol epoxide of benzo[a]pyrene are developed. The optimization procedure includes evaluation of the effect of buffer molarity, the pH of the buffer, and the role of organic modifiers. The method can be utilized to prepare standards with known absolute configuration that can be further used in the Randerath 32P-postlabeling procedure. PMID- 1460078 TI - Analytical and micropreparative separation of peptides by capillary zone electrophoresis using discontinuous buffer systems. AB - The tiny injection volumes that are usually necessary to maintain the high efficiency of capillary zone electrophoresis present a major problem if only limited sample amounts are available. To increase the sample load, discontinuous buffer systems were developed that allow the on-column concentration of dilute samples. Injection volumes can be increased in this way by at least a factor of 30. These stacking systems were applied to the analysis of tryptic peptides, to the purity checking of high-performance liquid chromatographic fractions and for the micropreparative separation of peptides with subsequent amino acid sequence analysis. PMID- 1460079 TI - Dynamin: motor protein or regulatory GTPase. PMID- 1460080 TI - Effects of 2,3-butanedione monoxime on the crossbridge kinetics in frog single muscle fibres. AB - The effects of 2,3-butanedione monoxime (BDM) on contraction characteristics were studied at 5 degrees C in single intact fibres isolated from the tibialis anterior muscle of the frog. The force-velocity relation was determined using the controlled-velocity method in either whole fibres or short fibre segments in which sarcomere shortening was measured by a laser light diffraction method. It is shown that 3 mM BDM decreases the speed of rise and the amount of tetanus tension, reduces the maximum velocity of shortening and increases the curvature of the force-velocity relation, as well as the value for the stiffness to tension ratio. BDM also slowed down the redevelopment of tetanus tension after a period of unloaded shortening both in fixed-end and in length-clamp conditions. In normal and in BDM-treated fibres length-clamping increased the speed of the initial rise of tetanus tension but not that of the recovery after shortening. The observed force-velocity data points were fitted by the Huxley (1957) equation. It was found that BDM produces a conspicuous decrease of the rate constant for crossbridge attachment. This effect, and also a reduction of the force per crossbridge, are responsible for the depression of the contractile characteristics produced by BDM. PMID- 1460081 TI - Two different acto-S1 complexes. AB - Based on change in anisotropy of fluorescently labelled S1 and on increase in turbidity of acto-S1 complex when S1 bound to F-actin, we reported previously that depending on the molar ratio of S1 to actin two different complexes of actin monomer (A) and myosin subfragment 1 (S1) could be formed: A1*S1 (one actin with one S1) and A2*S1 (two actins with one S1). Here we extend these findings to F actin labelled with pyrene and cross-linked to S1 with 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide (EDC). The fluorescence of pyrene F-actin decreased with increase in S1 concentration and reached saturation at a molar ratio of S1 to actin of either 0.5 or 1.0, depending on whether S1 was added slowly (5 min) or quickly (10-20 s between additions). Incubation of A2*S1 complex in excess of S1 for > 1 h caused a shift in equilibrium towards the A1*S1 complex. The A2*S1 complexes were not formed at high S1 to actin ratios (> 1.0) owing to competition between heads. Crosslinking experiments showed that the formation of EDC crosslinked products, 175-185 kDa doublet and 265 kDa band, depended on the ratio S1 to actin. To assess the relative ratio of S1 and actin in crosslinked products, we labelled S1 and F-actin with different fluorescent probes (5-IAF and IATR). The S1 to actin ratio was proportional to the ratio of intensities of fluorescence of labelled S1 and actin. The S1 to actin ratio in 265 kDa product was two times smaller than in 175-185 kDa doublet (which is believed to be A1*S1 complex) and therefore 265 kDa band corresponded to A2*S1. Transition between two types of binding may be important to understanding how muscle contracts. PMID- 1460082 TI - Early stages of myogenesis in a large mammal: formation of successive generations of myotubes in sheep tibialis cranialis muscle. AB - The generation of myotubes was studied in the tibialis cranialis muscle in the sheep hindlimb from the earliest stage of primary myotube formation until a stage shortly before muscle fascicles began to segregate. Primary myotubes were first seen on embryonic day 32 (E32) and reached their maximum number by E38. Small numbers of secondary myotubes were first identified at E38, and secondary myotube numbers continued to increase during the period of study. The ratio of adult muscle fibre to primary myotube numbers was approximately 70:1, making it seem unlikely that every later generation myotube used a primary myotube as scaffold for its formation, as described in small mammals. By E62, some secondary myotubes were supporting the formation of a third generation of myotubes. Experiments with diffusible dye markers showed that primary myotubes extended from tendon to tendon of the muscle, whereas most adult fibres ran for only part of the muscle length, terminating with myo-myonal attachments to other muscle fibres in a series arrangement. Acetylcholinesterase (AChE) and acetylcholine receptor (AChR) aggregations appeared in multiple bands across the muscle shortly after formation of the primary generation of myotubes was complete. The number of bands and their pattern of distribution across the muscle as they were first formed was the same as in the adult. Primary myotubes teased from early muscles had multiple focal AChE and AChR deposits regularly spaced along their lengths. We suggest that the secondary generation of myotubes forms at endplate sites in a series arrangement along the length of single primary myotubes, and that tertiary and possibly later generations of myotubes in their turn use the earlier generation myofibres as a scaffold. Although the fundamental cellular mechanisms appear to be similar, the process of muscle fibre generation in large mammalian muscles is more complex than that described from previous studies in small laboratory rodents. PMID- 1460084 TI - Tetragonal deformation of the hexagonal myofilament matrix in single skinned skeletal muscle fibres owing to change in sarcomere length. AB - Single skinned skeletal muscle fibres were immersed in solutions containing two different levels of activator calcium (pCa: 4.4; 6.0). Sarcomere length was varied from 1.6 to 3.5 microns and recorded by laser diffraction. Slack length was 2.0 microns. Small-angle equatorial X-ray diffraction patterns of relaxed and activated fibres at different sarcomere lengths were recorded using synchrotron radiation. The position and amplitude of the diffraction peaks were calculated from the spectra based on the hexagonal arrangement of the myofilament matrix, relating the position of the (1.0)- and (1.1)-diffraction peaks in this model by square root of 3. The diffraction peaks were fitted by five Gaussian functions (1.0, 1.1, 2.0, 2.1 and Z-line) and residual background was corrected by means of a hyperbola. The coupling of the position of the (1.0)- and (1.1)-peak was expressed as a factor: FAC = [d(1.0)/d(1.1)]/square root 3. In the relaxed state this coupling factor decreased at increasing sarcomere length (0.9880 +/- 0.002 at 2.0 microns; 0.900 +/- 0.01 at 3.5 microns). The coupling factor tends toward the one that will be obtained from the squared structure of actin filaments near the Z-discs. At shorter sarcomere lengths a decrease of the coupling factor has also been seen (0.9600 +/- 0.005 at 1.6 microns), giving rise to an increased uniform deformation of the hexagonal matrix, when sarcomere length is changed from slack length. From these experiments we conclude that a change in sarcomere length (from slack length) increases the deformation of the actin-myosin matrix to a tetragonal lattice. PMID- 1460083 TI - Myosin heavy chain composition of single fibres and their origins and distribution in developing fascicles of sheep tibialis cranialis muscles. AB - The myosin heavy chain (MHC) composition of single muscle fibres in developing sheep tibialis cranialis muscles was examined immunohistochemically with monoclonal antibodies to MHC isozymes. Data were collected with conventional microscopy and computerized image analysis from embryonic day (E) 76 to postnatal day (PN) 20, and from adult animals. At E76, 23% of the young myofibres stained for slow-twitch MHC. The number of these fibres considerably exceeded the number of primary and secondary myotubes. By E100, smaller fibres, negative for slow twitch MHC, encircled each fibre from the initial population to form rosettes. A second population of small fibres appeared in the unoccupied spaces between rosettes. Small fibres, whether belonging to rosettes or not, did not initially express slow-twitch MHC, expressing mainly neonatal myosin instead. These small fibres then diverged into three separate groups. In the first group most fibres transiently expressed adult fast myosin (maximal at E110-E120), but in the adult expressed slow myosin. This transformation to the slow MHC phenotype commenced at E110, was nearing completion by 20 postnatal days, and was responsible for approximately 60% of the adult slow twitch fibre population. In the other two groups expression of adult fast MHC was maintained, and in the adult they accounted for 14% (IIa MHC) and 17% (IIb MHC) of the total fibre numbers. We conclude that muscle fibre formation in this large muscle involves at least three generations of myotube. Secondary myotubes are generated on a framework of primary myotubes and both populations differentiate into the young myofibres which we observed at E76 to form rosettes. Tertiary myotubes, in turn, appear in the spaces between rosettes and along the borders of fascicles, using the outer fibres of rosettes as scaffolds. PMID- 1460085 TI - Novel immunological technique. PMID- 1460086 TI - A monoclonal antibody that recognizes different conformational states of skeletal muscle troponin C and other calcium-binding proteins. PMID- 1460087 TI - Galactose to ceramide linkage is essential for the binding of a polyclonal antibody to galactosyl ceramide. AB - Characterization of a polyclonal antibody to galactosyl ceramide (Gal-Cer) which inhibits the internalization and infection of HIV-1 in neural cell lines was carried out. Polyclonal antibody to Gal-Cer was produced by injecting rabbits with Gal-Cer liposomes. The specificity of anti-Gal-Cer binding was studied by high performance thin layer chromatography (HPTLC)-based immunoassay. Using natural and semisynthetic lipids, the specificity of anti-Gal-Cer interaction was studied. The antibody bound to Gal-Cer and its derivatives. The antibody did not bind to glucosyl ceramide or lactosyl ceramide. Glucosyl ceramide differs from Gal-Cer by a hydroxyl group at the fourth carbon and in lactosyl ceramide galactose is linked to ceramide by an intervening glucose molecule. This indicates that D-galactose linked to ceramide is essential for binding. Removal of fatty acid from Gal-Cer, as seen with N-palmitoyl- and N-oleoyl Gal-Cer, had no effect on the binding. It appears that the third carbon of Gal-Cer is not involved in the binding. This is supported by the binding of anti-Gal-Cer to sulfatide or GM4 in which sulfate or sialic acid are added at the third carbon of Gal-Cer, respectively. PMID- 1460088 TI - Immunochemical characterization of a monoclonal antibody specific for Alzheimer's disease associated protein. AB - In this study, the monoclonal antibody PHF-1 which recognizes epitopes unique to Alzheimer's disease associated proteins (ADAP) has been characterized. Crossed affinity immunoelectrophoresis was used to estimate the binding constant for the interaction of PHF-1 with ADAP and to estimate the fraction of PHF-1 reactive protein. The binding constant of PHF-1 was determined to be 1.3 x 10(-8) M. Furthermore, the effect of dephosphorylation on the electrophoretic pattern of the PHF-1 reactive protein and the ensuing changes in its immunoreactivity were demonstrated. PMID- 1460089 TI - Presynaptic inhibitory effect of TNF-alpha on the release of noradrenaline in isolated median eminence. AB - The effect of tumor necrosis factor-alpha (TNF-alpha) on the stimulation-evoked release of noradrenaline (NA) from isolated rat median eminence (ME) was investigated, using a low-volume perfusion system. Median eminence, loaded with [3H]noradrenaline, was superfused with Krebs solution and stimulated electrically (2 Hz, 120 shocks). The effect of TNF-alpha was studied on the S2/S1 ratio. It was found that stimulation-evoked release of NA from noradrenergic axon terminals in the isolated rat ME was inhibited by TNF-alpha and this effect was concentration-dependent. In contrast, TNF-alpha had no effect on the release of [3H]NA from the spleen. Since NA released in the ME might be involved in the modulation of corticotropin-releasing factor (CRF) production, it is suggested that TNF-alpha, through presynaptic modulation of NA release from noradrenergic nerve terminals in the ME, might regulate CRF and other neurohormone release in this hypothalamic structure. PMID- 1460091 TI - Expression of major histocompatibility complex (MHC) class I genes in astrocytes correlates with the presence of nuclear factors that bind to constitutive and inducible enhancers. AB - The molecular basis of constitutive and inducible major histocompatibility complex (MHC) class I gene expression was studied in murine astrocytes in primary culture. Astrocytes constitutively expressed MHC class I molecules and treatment of these cells with interferon-gamma (IFN-gamma) further induced expression. The conserved region containing the upstream MHC class I regulatory element (MHC-CRE) and juxtaposed interferon consensus sequence (ICS) enhanced constitutive MHC class I promoter activity. As seen with cell surface expression of MHC molecules, treatment of astrocytes with IFN-gamma increased MHC class I promoter activity. Inducible expression required the presence of the MHC-CRE/ICS enhancer region. Nuclear factors that bind to the MHC-CRE and ICS were constitutively expressed in cultured astrocytes and IFN-gamma treatment further induced binding activity both to the MHC-CRE and ICS and correlated with induction of MHC class I gene expression. This study identifies the MHC-CRE and ICS as the major cis elements in controlling MHC class I promoter activity and suggests that the expression of nuclear factor binding activities to these enhancer elements is a basic transactivating mechanism for the expression of MHC class I genes in astrocytes. PMID- 1460090 TI - Human glioblastoma cell line 86HG39 activates T cells in an antigen specific major histocompatibility complex class II-dependent manner. AB - The capacity of three different human glioblastoma cell lines to activate human T cells was analysed by measuring major histocompatibility complex (MHC) antigen expression, monokine secretion and lectin, mAb OKT3 and antigen-driven T cell proliferation. All glioblastoma cells tested were able to induce PHA and concanavalin A (ConA)-driven T cell proliferation in a dose-dependent fashion, while all failed to induce T cell activation with mAb OKT3. In addition, the glioblastoma cell line 86HG39 was able to induce tetanus toxoid and toxoplasma lysate antigen-specific T cell proliferation. The responding T cell lines originated from only one out of five different donors. This foreign antigen specific T cell proliferation induced by 86HG39 cells could be inhibited with mAb L243 directed against HLA-DR molecules. The study of monokine secretion by 86HG39 cells showed a strong interleukin (IL)-6 secretion after lipopolysaccharide (LPS) treatment, whilst no IL-1 secretion was observed. Furthermore, only 86HG39 cells were positive for HLA-DR molecules, whereas interferon (IFN) gamma treatment of 87HG28 and 87HG31 cells was necessary for the induction of class II antigen expression. Thus, cell line 86HG39 shows many features of an antigen presenting cell and the interaction of these cells with MHC compatible human T cells might be a useful model to study cellular immune reactions within the central nervous system. PMID- 1460092 TI - Type I interleukin-1 receptors in the mouse brain-endocrine-immune axis labelled with [125I]recombinant human interleukin-1 receptor antagonist. AB - Iodine-125-labelled recombinant human interleukin-1 (IL-1) receptor antagonist ([125I]IL-1ra) was utilized to further determine the characteristics of IL-1 receptors in the brain-endocrine-immune axis. The binding of [125I]IL-1ra in homogenates of mouse hippocampus, spleen and testis was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity (KD, 20-30 pM). In competition studies, IL-1ra, recombinant human IL-1 alpha, IL 1 beta and a weak IL-1 beta analog inhibited [125I]IL-1ra binding to mouse tissues in parallel with their biological activities. In autoradiographic studies, [125I]IL-1ra and [125I]IL-1 alpha binding showed comparable distribution patterns with highest densities of binding sites present in the dentate gyrus of the hippocampus, choroid plexus, anterior pituitary, marginal zones and red pulp regions of the spleen, epididymis and interstitial area of the testis. The binding characteristics and distribution of [125I]IL-1ra are comparable to those of previously characterized Type I IL-1 receptors. These data provide further support for a role for IL-1 in coordinating brain-endocrine-immune responses to physiological and pharmacological stimuli. PMID- 1460093 TI - Specific immunotherapeutic strategy for myasthenia gravis: targeted antigen presenting cells. AB - The pathogenesis of myasthenia gravis (MG) involves a T cell-dependent antibody mediated autoimmune response directed against acetylcholine receptors (AChR). Inactivation of AChR-specific T cells should interrupt the immune response, resulting in therapeutic benefit. Since each individual's repertoire of T cells responds to a heterogeneous and unique spectrum of AChR epitopes presented in association with self-major histocompatibility complex (MHC) class II, an individualized approach is required to target all relevant AChR-specific T cells. The individual's own antigen-presenting cells (APC) can be used for this purpose, since they process and present the antigen appropriately, and express the correct MHC class II. A novel method of binding AChR to surface immunoglobulin with a heterobifunctional antibody conjugate allows us to use all B cells as APC. Conjugate-plus-AChR-treated B cells (AChR-APC) effectively targeted AChR-specific T cells, stimulating vigorous proliferative responses in a rat cell culture system. If APCs are 'fixed' with cross-linking reagents, they induce long-lasting or permanent 'anergy' of the specific T cells. We prepared AChR-APC, allowed them to process AChR in vitro, and fixed them with paraformaldehyde. Pre-culture of these fixed AChR-APC with AChR-specific T cells induced anergy: when restimulated with fresh AChR-APC, the T cells exhibited markedly reduced proliferative responses and IL-2 production, compared with responses of T cells pre-cultured with control fixed B cells. Implications for the design of antigen-specific therapeutic strategies for MG and other immune disorders will be discussed. PMID- 1460094 TI - Identification of a 58-kDa antigen with increased immunoreactivity in the cerebella of multiple sclerosis patients. AB - An increase in immunoreactivity associated with a 58-kDa antigen was found in a majority of MS cerebellar homogenates examined by Western blot analysis using antisera obtained by selective immunization of rabbits with autopsy cerebella. Two-dimensional immunoblotting demonstrated that the majority of the increased immunoreactivity observed in MS cerebella was associated with the highest apparent pI of three immunoreactive species at 58 kDa. Immuno-crossreaction with rat cerebellar homogenates demonstrated that the 58-kDa antigen was developmentally regulated, showing the greatest immunoreactivity at embryonic day 15. The 58-kDa cerebellar antigen may represent a membrane protein which is re expressed as part of the onset of MS. PMID- 1460095 TI - Microglial cell upregulation of HIV-1 expression in the chronically infected promonocytic cell line U1: the role of tumor necrosis factor-alpha. AB - Culture supernatants from lipopolysaccharide (LPS)-treated murine microglial cells were found to markedly induce the expression of human immunodeficiency virus (HIV)-1 in the chronically infected human promonocytic cell line U1 as detected by measurements of HIV-1 p24 antigen release into U1 culture supernatants. Antibody to tumor necrosis factor (TNF)-alpha had an inhibitory effect on the induction of virus by microglial cell supernatants. Also, treatment of microglia with pentoxifylline, an inhibitor of TNF-alpha production, resulted in suppressed amounts of TNF in the supernatants of LPS-treated microglia and in a reduced stimulatory capacity of these supernatants on HIV-1 expression in U1 cells. These findings support the concept that TNF-alpha production by glial cells plays a pathogenetic role in HIV-1-associated brain disease by promoting the expression of the virus in infected cells. PMID- 1460096 TI - Evidence of a neurogenic component during IgE-mediated inflammation in mouse skin. AB - IgE-mediated inflammation was measured in mouse footpads that lacked sciatic innervation. Mice were passively sensitized with a monoclonal antibody, IgE anti dinitrophenol, or were immunized for specific IgE production. Antigen-induced swelling in the denervated footpads was reduced 23-39% when compared to sham or untreated controls. Reduced IgE-mediated swelling responses were attributed to the loss of a mast cell-nerve interaction and not to blood vessel sensitivity to vasoamines. Furthermore, electrical stimulation of the distal segment of the sciatic nerve completely restored IgE-mediated inflammation. These data provide in vivo evidence that peripheral nerves participate in cutaneous IgE-mediated swelling reactions with the net effect of increasing inflammation. PMID- 1460097 TI - Assessing treatment acceptance: the Abbreviated Acceptability Rating Profile. AB - As part of a broad focus on service accountability, increased attention has been devoted to the assessment of consumer judgments of treatment acceptability. Current treatment acceptability measures are limited by item complexity and time intensiveness. These limitations were addressed with the modification of an existing instrument (Intervention Rating Profile; Witt & Elliott, Journal of Abnormal Child Psychology, 13, 59-67, 1985). Psychometric support was found for the revised measure (Abbreviated Acceptability Rating Profile; AARP) in an initial sample of parents (N = 60) who rated child treatments. Results were replicated in a cross-validation study of a second independent sample of parents (N = 80). A third sample of subjects was used to assess the time-intensiveness and readability of the AARP. The usefulness of the modified instrument is discussed. PMID- 1460098 TI - Some relevant components of adherence behavior. AB - Adherence to medical or psychological prescriptions is analyzed as a type of rule and self-rule following behavior. Variables that increase the likelihood of compliance are: (1) the specific motivational condition, usually aversive when treatment or preventive prescription is sought, (2) the medium of contact and context used when receiving the prescription, (3) attentive responses under the control of the prescription, (4) understanding the complexity of the prescription, (5) the specific content of the prescription, (6) verbalization on the willingness to follow the prescription, (7) appropriate abilities for producing the behaviors described in the prescription, (8) physical facilities and appropriate biological conditions for producing the behaviors, (9) verbalization describing the relationship between the adherence response and the immediate and long-term consequences, functioning as a discriminative stimulus and as a reinforcing event, (10) compatibility between daily activities and the behaviors described in the prescription: response cost and self-control behavior when several behaviors are possible and probable. Strategies which facilitate self-control as well as incompatible behavior are suggested. PMID- 1460099 TI - The case of a newspaper phobia in a 9-year-old child. AB - The case of E, a 9-year-old, male, with a newspaper phobia, is presented. The phobia developed over a 4-year period and gradually spread until it included many significant areas of E's life. Treatment took place over a 4-month period. It involved use of a token economy administered by E's parents. Cognitively, the treatment involved the concepts of the acquisition of perceived self-control as a consequence of the token economy agreement. This included volition, attention, and self-control by E as well as parental reinforcement. PMID- 1460100 TI - Extinction and DRO in the treatment of aggression in a boy with severe mental retardation. AB - A novel use of extinction was applied in combination with differential reinforcement of other behavior to reduce dangerous levels of aggression displayed by an 11-year-old boy with severe mental retardation and cerebral palsy. Data taken during actual treatment sessions and in the client's "natural" environment (classroom and dormitory) suggest that the intervention was immediately effective and that the improvements were maintained and generalized. PMID- 1460101 TI - B. F. Skinner and the cognitive revolution. AB - The behaviorism that cognitive scientists attack is a caricature, drawn primarily from the more polemical writings of J. B. Watson and B. F. Skinner. In this brief commentary, I discuss the fact that these writings, and especially Skinner's, offered the neocognitivists such a polar difference from their own position, that it was easier to ignore the distinction between behaviorism and neobehaviorism than to recognize it. I point out that there are factors in Skinner's intellectual history that may account for the emergence of his more radical behaviorism out of what was essentially his own theoretical, neobehavioristic approach to the study of conditioning and learning. PMID- 1460102 TI - Listening to our clinical partners: informing researchers about children's fears and phobias. AB - We surveyed a national sample of clinical psychologists to expand on Graziano and De Giovanni's (Behaviour Research and Therapy, 1979, 17, 161-162) findings that 6.8% of clinically referred children present with problems with fears and/or phobias. The survey was also conducted to assess how clinicians could inform researchers about current needs for investigations in this area. Questions involved epidemiological, demographical, and treatment characteristics of cases recently seen by therapists. The percentage of referred cases for fears/phobias in children was determined to be similar over time. In addition, types of fears, length of history of fear, intensity of fear, length of treatment, types of treatments used, and degree of parental involvement were measured and reported. The results were found to suggest a substantial degree of heterogeneity among types of fears and treatment methods for this population, as well as important lines of future research. They also suggest the need for controlled studies to assess the efficacy of a number of widely used treatments that lack an empirical base. PMID- 1460103 TI - Dietary restraint anxiety and its relationship to human eating behavior. AB - Ninety-five female university students completed Stunkard and Messick's (Journal of Research Psychosomatic Research, 29, 71-83, 1985) Three-Factor Eating Questionnaire, measuring three dimensions of human eating behavior: cognitive restraint, disinhibition, and hunger susceptibility. They were led through the visualization of a neutral or pleasant scene and a food scene, but were instructed that they would not be able to eat the food. Only hunger susceptibility was found to be significantly correlated with ratings of subjective anxiety (SUDS) and urge to eat in the not eating situation after any variability associated with the neutral scene was removed. That is, internal (hunger) and external (incentive) cues when linked to not eating are sources of anxiety. Treatment programmes for obesity might well include desensitization of these cues. PMID- 1460104 TI - The non-standardization of the Fear Survey Schedule. AB - The Fear Survey Schedule-III was administered to 860 college students. The results are presented in the form of frequencies, in deliberate contrast to previous work which present results in the form of z-scores. The argument is made that these z-scores do not normalize the original item distributions and thus provide no opportunity for normative comparisons. Data are provided allowing the researcher to assess the characteristics of FSS-III item distributions and make limited normative comparisons. PMID- 1460105 TI - Improving parent-child interactions for families of children with developmental disabilities. AB - Child Management Training (CMT) involves compliance training with a focus on consistent use of antecedents and consequences. Planned Activities Training (PAT) focuses on teaching parents to plan for and engage in activities with their children. A multiple probe design counterbalancing PAT and CMT showed that PAT and CMT were about equally effective in improving mother-child interactions in four families with children with developmental disabilities. Responses to a social validation questionnaire indicated that parents were satisfied with the services received, and that PAT was the slightly preferred treatment. Prior research demonstrated that PAT enhanced the results of CMT. The practical advantages of PAT over CMT are discussed. PMID- 1460106 TI - Sylvian fissure morphology and asymmetry in men and women: bilateral differences in relation to handedness in men. AB - The anatomy of the sylvian fissure in the human brain was studied to develop reliable criteria for anatomical landmarks of the posterior part of the fissure for use in its definition and measurement; to quantify right-left asymmetries in segments of the sylvian fissure; to assess whether any anatomical features are associated with hand preference (selected as one index of hemispheric functional asymmetry); and whether structure-function relationships are similar in men and women. A sample of 67 brain specimens (24 men and 43 women, mean age = 53 years) was studied postmortem (with the aid of dissection) from people who had been tested before death for detailed hand preference. Sylvian fissure anatomy in the human brain is very variable and no agreement exists as to the point of its posterior termination. The posterior ascending ramus, originating at the posterior bifurcation of the fissure, was found to be the continuation of the main limb of the sylvian fissure. Three segments of the sylvian fissure were defined and measured: anterior, horizontal, and vertical. The anterior segment showed no asymmetry; the horizontal segment was twice as large on the left side as on the right; and the vertical segment twice as large on the right. The two asymmetries counterbalanced each other, and overall asymmetry in the posterior region (horizontal plus vertical) was minimal. The basic asymmetry is in the position at which the fissure turns up, resulting in the different extent and position of the surrounding right and left parietal and temporal gyri and associated cytoarchitectonic regions. The possible embryological course of the asymmetry is discussed. Handedness correlated with anatomy of the sylvian fissure in men. In contrast to general expectation, hand preference was associated with a bilateral feature of morphology, and not with less asymmetry in non-right handers. Men having consistent-right-hand preference had longer horizontal segments in both hemispheres compared to men not having consistent-right-hand preference. The direction and magnitude of asymmetry did not differ between the two male hand-preference groups. Since hand preference is an index of other motor and perceptual functions which are asymmetrically represented in the two hemispheres in gyri surrounding the sylvian fissure, it is suggested that anatomy of the sylvian fissure is related to functional asymmetries in men. A sex difference in structure-function relationship was observed. No association was found between hand preference and sylvian fissure anatomy in women.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1460107 TI - Cytoarchitecture and neural afferents of orbitofrontal cortex in the brain of the monkey. AB - The orbitofrontal cortex of the monkey can be subdivided into a caudal agranular sector, a transitional dysgranular sector, and an anterior granular sector. The neural input into these sectors was investigated with the help of large horseradish peroxidase injections that covered the different sectors of orbitofrontal cortex. The distribution of retrograde labeling showed that the majority of the cortical projections to orbitofrontal cortex arises from a restricted set of telencephalic sources, which include prefrontal cortex, lateral, and inferomedial temporal cortex, the temporal pole, cingulate gyrus, insula, entorhinal cortex, hippocampus, amygdala, and claustrum. The posterior portion of the orbitofrontal cortex receives additional input from the piriform cortex and the anterolateral portion from gustatory, somatosensory, and premotor areas. Thalamic projections to the orbitofrontal cortex arise from midline and intralaminar nuclei, from the anteromedial nucleus, the medial dorsal nucleus, and the pulvinar nucleus. Orbitofrontal cortex also receives projections from the hypothalamus, nucleus basalis, ventral tegmental area, the raphe nuclei, the nucleus locus coeruleus, and scattered neurons of the pontomesencephalic tegmentum. The non-isocortical (agranular-dysgranular) sectors of orbitofrontal cortex receive more intense projections from the non-isocortical sectors of paralimbic areas, the hippocampus, amygdala, and midline thalamic nuclei, whereas the isocortical (granular) sector receives more intense projections from the dorsolateral prefrontal area, the granular insula, granular temporopolar cortex, posterolateral temporal cortex, and from the medial dorsal and pulvinar thalamic nuclei. Retrograde labeling within cingulate, entorhinal, and hippocampal cortices was most pronounced when the injection site extended medially into the dysgranular paraolfactory cortex of the gyrus rectus, an area that can be conceptualized as an orbitofrontal extension of the cingulate complex. These observations demonstrate that the orbitofrontal cortex has cytoarchitectonically organized projections and that it provides a convergence zone for afferents from heteromodal association and limbic areas. The diverse connections of orbitofrontal cortex are in keeping with the participation of this region in visceral, gustatory, and olfactory functions and with its importance in memory, motivation, and epileptogenesis. PMID- 1460108 TI - Ultrastructural and immunocytochemical study of lamina II islet cells in rat spinal dorsal horn. AB - In order to compare the ultrastructure of GABA-immunoreactive and nonimmunoreactive islet cells in lamina II of the rat dorsal horn, a combined ultrastructural and immunocytochemical study of nine Golgi-stained neurones was performed. Cell bodies of these neurones were tested with antiserum to GABA, and in most cases with antiserum to glycine, while parts of the cell body and dendritic tree were examined with the electron microscope. Four of the neurones had cell bodies that were immunoreactive with GABA antiserum, and 2 of these were also glycine-immunoreactive, while 2 were not. Cell bodies of the remaining five neurones were not immunoreactive with GABA antiserum, nor, in the 3 cases tested, with glycine antiserum. Three of the GABA-immunoreactive cells possessed vesicle containing dendrites and were presynaptic at dendrodendritic synapses, whereas no vesicles were observed in the dendrites of any of the neurones that were not GABA immunoreactive. The axon of one of the nonimmunoreactive cells was found with the electron microscope. It gave rise to boutons that contained round agranular vesicles and a few dense-cored vesicles. Three synapses formed by this axon were identified and all were asymmetric. No obvious differences were detected in the types of profile that were presynaptic to GABA-immunoreactive and nonimmunoreactive cells. These results suggest that GABAergic islet cells are a source of presynaptic dendrites in lamina II of the rat and that some presynaptic dendrites contain GABA and glycine, while others contain GABA without glycine. The nonimmunoreactive islet cells presumably represent a distinct functional class of neurones and some of these may release an excitatory amino acid transmitter, possibly in addition to one or more neuropeptides. PMID- 1460109 TI - The auditory cortex of the mouse: connections of the ultrasonic field. AB - The cortical and subcortical connections of the ultrasonic field (UF) of the auditory cortex of the house mouse (Mus musculus) were studied by using retrograde and anterograde transport of horseradish peroxidase (HRP). Small amounts of HRP were locally injected into the electrophysiologically defined UF. Superficial (layer I-IV) and deep (layer IV-VI) injections were prepared. Superficial injections led to labelling of both cells (retrograde) and terminals (anterograde) in areas of the ipsilateral primary and secondary auditory cortex and in its dorsoposterior field, in an ipsilateral dorsal association area (patches of label), probably in ipsilateral secondary somatosensory cortex, in the contralateral homotopic UF, and in the ipsilateral medial geniculate body (MGBv, MGBd, and MGBm) and caudal posterior nucleus complex. Deep injections showed the same connectivities as superficial ones and, in addition, terminals in the very caudal caudatoputamen, in the nucleus limitans and the nucleus reticularis of the thalamus, in the rostral pole, the dorsomedial, and lateral nucleus of the inferior colliculus, in the stratum griseum intermediale of the superior colliculus, and in a pontine nucleus ventromedial of the lateral lemniscus. All these projections occurred only ipsilaterally. The majority of connections, except those with the nucleus limitans, superior colliculus and pontine nucleus, suggest that UF is part of the primary anditory cortex (AI) and/or of the anterior anditory field (AAF) of the auditory cortex. Since UF has no regular tonotopy, this has important implications for the functional role that AI/AAF can have in communication-sound analysis. PMID- 1460110 TI - Immunohistochemical localization of ryanodine binding proteins in the central nervous system of gymnotiform fish. AB - The ryanodine receptor, an integral membrane protein of the sarcoplasmic reticulum in muscle, embodies a high conductance channel permeable to calcium ions. Recent studies have identified ryanodine-binding proteins in avian and mammalian central nervous systems. These neuronal ryanodine receptors appear to function as Ca2+ channels which may gate the release of Ca2+ from caffeine sensitive intracellular pools in neurons. In the present investigation, we employed monoclonal antibodies against ryanodine-binding proteins of avian muscle cells to the brain of weakly electric gymnotiform fish. Immunoprecipitation and Western blot analysis revealed two isoforms in the fish brain, with molecular weights comparable to those of avian and fish muscle ryanodine-binding proteins. By employing immunohistochemical techniques, we mapped these proteins in fish brain. Ryanodine receptor-like immunoreactivity was found in nerve cell bodies as well as dendrites and axonal processes. The ryanodine-binding protein is distributed throughout the neuraxis in specific cell types of the gymnotiform brain. In the telencephalon, immunoreactive cells were found in the glomerular layer of the olfactory bulb, in the supracommissural subdivision of the ventral telencephalon, and in the intermediate rostral subdivision of the ventral telencephalon. In the diencephalon, immunoreactive cells or fibers were observed in the nucleus prethalamicus and the habenula, within the nucleus at the base of the optic tract and the adjacent dorsal tegmental nucleus, the pretectal nuclei A and B, and the nucleus electrosensorius. In addition, immunopositive cells were seen in several nuclei of the hypothalamus, with the inferior and lateral subdivision of the nucleus recessus lateralis displaying the highest concentration of neurons. In the mesencephalon, the optic tectum contained the greatest number of immunopositive cells. In the rhombencephalon, labelling was seen in the nucleus of the lateral valvula, central gray, lateral tegmental nucleus, in boundary cells of the nucleus praeminentialis, efferent octavolateral nucleus, an area adjacent to the medial edge of the lateral reticular nucleus, nucleus medialis, and electrosensory lateral line lobe. As in avian brain, cerebellar Purkinje cells were positive for ryanodine-binding protein, although only subsets of Purkinje cells were labelled. PMID- 1460111 TI - Synaptic connections of the narrow-field, bistratified rod amacrine cell (AII) in the rabbit retina. AB - The synaptic connections of the narrow-field, bistratified rod amacrine cell (AII) in the inner plexiform layer (IPL) of the rabbit retina were reconstructed from electron micrographs of continuous series of thin sections. The AII amacrine cell receives a large synaptic input from the axonal endings of rod bipolar cells in the most vitreal region of the IPL (sublamina b, S5) and a smaller input from axonal endings of cone bipolar cells in the scleral region of the IPL (sublamina a, S1-S2). Amacrine input, localized at multiple levels in the IPL, equals the total number of synapses received from bipolar cells. The axonal endings of cone bipolar cells represent the major target for the chemical output of the AII amacrine cell: these synapses are established by the lobular appendages in sublamina a (S1-S2). Ganglion cell dendrites represent only 4% of the output of the AII amacrine and most of them are also postsynaptic to the cone bipolars which receive AII input. The AII amacrine is not presynaptic to other amacrine cells. Finally, the AII amacrine makes gap junctions with the axonal arborizations of cone bipolars that stratify in sublamina b (S3-S4) as well as with other AII amacrine cells in S5. Therefore, in the rabbit retina 1) the rod pathway consists of five neurons arranged in series: rod-->rod bipolar-->AII amacrine-->cone bipolar-->ganglion cell; 2) it seems unlikely that a class of ganglion cells exists that is exclusively devoted to scotopic functions. In ventral, midperipheral retina, about nine rod bipolar cells converge onto a single AII amacrine, but one of them establishes a much higher proportion of synaptic contacts than the rest. Conversely, each rod bipolar cell diverges onto four AII amacrine cells, but one of them receives the largest fraction of synapses. Thus, within the pattern of convergence and divergence suggested by population studies, preferential synaptic pathways are established. PMID- 1460112 TI - Three-dimensional analysis of the structure and composition of CA3 branched dendritic spines and their synaptic relationships with mossy fiber boutons in the rat hippocampus. AB - This paper is the third in a series to quantify differences in the composition of subcellular organelles and three-dimensional structure of dendritic spines that could contribute to their specific biological properties. Proximal apical dendritic spines of the CA3 pyramidal cells receiving synaptic input from mossy fiber (MF) boutons in the adult rat hippocampus were evaluated in three sets of serial electron micrographs. These CA3 spines are unusual in that they have from 1 to 16 branches emerging from a single dendritic origin. The branched spines usually contain subcellular organelles that are rarely found in adult spines of other brain regions including ribosomes, multivesicular bodies (MVB), mitochondria, and microtubules. MVBs occur most often in the spine heads that also contain smooth endoplasmic reticulum, and ribosomes occur most often in spines that have spinules, which are small nonsynaptic protuberances emerging from the spine head. Most of the branched spines are surrounded by a single MF bouton, which establishes synapses with multiple spine heads. The postsynaptic densities (PSDs) occupy about 10-15% of the spine head membrane, a value that is consistent with spines from other brain regions, with spines of different geometries, and with immature spines. Individual MF boutons usually synapse with several different branched spines, all of which originate from the same parent dendrite. Larger branched spines and MF boutons are more likely to synapse with multiple MF boutons and spines, respectively, than smaller spines and boutons. Complete three-dimensional reconstructions of representative spines with 1, 6, or 12 heads were measured to obtain the volumes, total surface areas, and PSD surface areas. Overall, these dimensions were larger for the complete branched spines than for unbranched or branched spines in other brain regions. However, individual branches were of comparable size to the large mushroom spines in hippocampal area CA1 and in the visual cortex, though the CA3 branches were more irregular in shape. The diameters of each spine branch were measured along the cytoplasmic path from the PSD to the origin with the dendrite, and the lengths of branch segments over which the diameters remained approximately uniform were computed for subsequent use in biophysical models. No constrictions in the segments of the branched spines were thin enough to reduce charge transfer along their lengths.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1460113 TI - GAD- and GABA-immunoreactivity in the ascending auditory pathway of horseshoe and mustached bats. AB - A comparative study of the immunostain to antibodies directed against glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in the ascending auditory pathway was carried out in horseshoe bats (Rhinolophus rouxi) and mustached bats (Pteronotus parnellii). In both species GAD/GABA-positive puncta (presumed axonal boutons) and GAD/GABA-positive cells were found in the cochlear nucleus, the superior olivary complex, the nuclei of the lateral lemniscus the inferior colliculus, and the medial geniculate body. General features of the immunostaining pattern in the auditory pathway agree with observations in other mammals. Quantitative analysis of puncta distribution shows that many auditory centers are characterized by subregional differences in puncta density and distribution. This indicates local differences in putatively inhibitory input related to connectivity and tonotopic organization. The following species characteristic features were found: 1) The dorsal non-laminated portion of the dorsal cochlear nucleus in horseshoe bats lacks the GAD/GABA-immunoreactive cells typical for the ventral laminated portion and the dorsal cochlear nucleus of other species. Clearly, a cytoarchitectonic specialization is accompanied by a loss of putatively GABAergic local inhibitory circuits. 2) The ventral division of the medial geniculate body of the mustached bat lacks GAD/GABA-immunopositive cells. Such cells are present in the horseshoe bat and other mammals. This finding implies functional differences in the organization of the medial geniculate body within the same mammalian order. PMID- 1460114 TI - Fine structure of rat septohippocampal neurons: II. A time course analysis following axotomy. AB - Previous light microscopic immunocytochemical studies with antibodies against transmitter-synthesizing enzymes have suggested that septohippocampal neurons undergo retrograde degeneration following transection of their axons by cutting the fimbria-fornix. However, a fine-structural analysis of the degeneration process in these cells is lacking so far. Here we have identified septohippocampal neurons by retrograde tracing with Fluoro-Gold. Thereafter, the fimbria-fornix was transected bilaterally. Fine-structural changes in prelabeled septohippocampal neurons were then studied after varying survival times up to 10 weeks. Examination under the fluorescence microscope of Vibratome sections through the septal region revealed numerous retrogradely labeled cells after all survival times following axotomy. These neurons were then intracellularly injected with the fluorescent dye Lucifer Yellow in order to stain their dendritic arbor. Many cells were found after each survival time that displayed characteristics of septohippocampal neurons in control rats (see Naumann et al., J Comp Neurol 325:207-218, 1992). In addition, increasing with survival time, there were many shrunken neurons with a reduced dendritic arbor. Representative examples of both normal appearing and shrunken neurons were photoconverted for subsequent electron microscopic analysis. Relatively few signs of neuronal degeneration were found at each survival time analyzed. The majority of cells, including the heavily shrunken ones, displayed fine-structural characteristics of normal neurons. However, a few degenerating neurons and reactive glial cells were present in all survival stages. We conclude that axotomized septohippocampal projection neurons cease the expression of transmitter-synthesizing enzymes and shrink, but many more cells survive for extended periods of time without target derived neurotrophic factor than was assumed in previous light microscopic studies. PMID- 1460115 TI - Neuroepithelial cells in the rat spinal cord express glutamate decarboxylase immunoreactivity in vivo and in vitro. AB - It is unknown whether neuroepithelial cells in the mammalian central nervous system express neurotransmitter-synthesizing enzymes. In this study, expression of glutamate decarboxylase (GAD), the gamma-aminobutyric acid (GABA)-synthesizing enzyme, was examined in proliferative cells and postmitotic neuroblasts in embryonic rat spinal cord. Immunostaining coronal sections of the embryonic spinal cord with K2 antiserum, which recognizes GAD proteins encoded by the GAD67 gene, revealed intensely stained neuroepithelial cells in the basal plate at embryonic day (E) 13, in the intermediate plate between E 13-16, and last seen in the alar plate at E 16. Nissl counterstaining demonstrated that a small number of these GAD-immunoreactive cells adjacent to the neural tube lumen were mitotic. The ventral-to-dorsal gradient of GAD expression in precursor cells and postmitotic neuroblasts correlates anatomically and temporally with the sequential generation of motoneurons, commissural neurons, and interneurons in the dorsal horn. Some of these GAD-immunoreactive neuroepithelial cells may re enter the mitotic cycle, while others are postmitotic neuroblasts presumably migrating to the intermediate zone to differentiate into young neurons. Double immunostaining cells acutely dissociated from E 11-18 spinal cords with K2 and anti-bromodeoxyuridine antisera, following a bromodeoxyuridine pulse in vivo, revealed considerable numbers of DNA-synthesizing cells immunoreactive for GAD. The absolute number of double-stained cells peaked during E 12-15, coinciding with terminal cell division in most spinal neurons. These observations suggest that spinal neuronal precursors can synthesize GAD-related proteins prior to, or during, the terminal cell cycle. Although GAD immunoreactivity revealed by K2 antiserum was detected in proliferative cells and in migrating postmitotic neuroblasts, GABA immunoreactivity was never detectable in these cells. These early embryonic GAD-immunoreactive neuroepithelial cells may either synthesize levels of GABA that cannot be detected immunocytochemically, and/or express enzymatically inactive GAD-related proteins. PMID- 1460116 TI - Transient expression of GABA immunoreactivity in the developing rat spinal cord. AB - The development of GABAergic neurons in the spinal cord of the rat has been investigated by immunocytochemical staining of frozen sections with anti-gamma aminobutyric acid (GABA) antiserum. In the cervical cord, GABA-immunoreactive fibers first appeared at embryonic day (E) 13 in the presumptive white matter within the ventral commissure, ventral funiculus, and dorsal root entrance zone, and in the ventral roots. There were no GABA-immunoreactive cell bodies detected at this age. By E14, motoneurons, the earliest generated spinal cells, were the first cell population to become GABA-immunoreactive at the cell body level. Thereafter, GABA-immunoreactive neurons increased progressively in number and extended from ventral to dorsal regions. GABA-immunoreactive relay neurons within lamina I of the dorsal horn were initially detected at E17. Interneurons in the substantia gelatinosa, the latest generated cells in the spinal cord, were also the last to express the GABA immunoreactivity at E18. Immunoreactive neurons peaked in intensity and extent at E18 and 19. GABA immunoreactivity was only detectable in neurons within the intermediate and marginal zones 1-3 days after they withdrew from the cell cycle. This contrasts to glutamate decarboxylase immunoreactivity, which is detected in precursor cells in the ventricular zone prior to, or during, withdrawal from the cell cycle. Toward the end of gestation, GABA immunoreactivity declined in intensity and extent. This regression began in the ventral horn of the cervical region and ended in the dorsal horn of the lumbosacral region. During the first week after birth, immunoreactivity in motoneurons and in many other neurons within the ventral horn, intermediate gray, and deeper layers of the dorsal horn disappeared, and only in those neurons predominantly within the superficial layers of the dorsal horn did it persist into adulthood. Thus, the expression and regression of GABA immunoreactivity in the spinal cord followed ventral-to-dorsal, rostral-to-caudal, and medial-to lateral gradients. These observations indicate that the majority of embryonic spinal neurons pass through a stage of transient expression of GABA immunoreactivity. The functional significance of this transient expression is unknown, but it coincides with the period of intense neurite growth of motoneurons, sensory neurons, and interneurons, and of neuromuscular junction formation, suggesting that the transient presence of GABA may play an important role in the differentiation of sensorimotor neuronal circuits. PMID- 1460117 TI - Sexual dimorphism in the vasotocin system of the bullfrog (Rana catesbeiana). AB - Arginine vasotocin (AVT) is widespread in amphibian brains, where its levels have been correlated with reproductive behaviors. To better understand which neural systems are involved in central actions of AVT, we used immunocytochemistry to compare the distribution of AVT in the brains of male and female bullfrogs (Rana catesbeiana). AVT-immunoreactive cells were observed in the septal nucleus, amygdala pars lateralis, magnocellular preoptic area, suprachiasmatic nucleus, and hypothalamus. AVT-immunoreactive cells were also found in the pretrigeminal nucleus, but only in animals killed in the fall. Immunoreactive fibers were broadly distributed in hypothalamic and extrahypothalamic areas. The most obvious sex differences were found in the amygdala pars lateralis, where the density of immunoreactive cells and fibers was significantly greater in male than in female bullfrogs. In addition, in the habenular nucleus, males had a denser distribution of AVT-immunoreactive fibers than females. In the suprachiasmatic nucleus, AVT immunoreactive cells were larger in females than in males but did not differ in number. Since the areas that showed sex differences in AVT distribution have also been implicated in control of reproductive behaviors, they may form the neural substrates for the effects of AVT on sexually dimorphic behaviors in amphibians. PMID- 1460118 TI - Topical isotretinoin for photodamaged skin. AB - Photodamaged skin is characterized clinically by coarseness, telangiectasia, wrinkling, discrete hyperpigmented and hypopigmented macules, atrophy, and ultimately the development of neoplasms. Studies on the UVB-irradiated hairless mouse indicate that topical application of tretinoin or isotretinoin induces structural modifications at the dermal level. Clinical trials indicate that tretinoin improves skin appearance in patients who have photodamage. This double blind, vehicle-controlled clinical trial was conducted to determine whether 36 weeks of treatment with topical isotretinoin improves mildly to moderately photodamaged facial skin. After they gave written informed consent 776 patients were randomly assigned to 36 weeks of treatment with either vehicle cream or isotretinoin cream, applied once nightly. Efficacy was evaluated by means of physician and patient assessment and a blinded analysis of standardized photographs taken before and after treatment. When compared with vehicle, treatment with isotretinoin resulted in statistically significant improvement in overall appearance, fine wrinkling, discrete pigmentation, sallowness, and texture. Isotretinoin cream was well tolerated. PMID- 1460119 TI - Pharmacokinetics and drug interactions of etretinate and acitretin. AB - Acitretin, the metabolite of etretinate, is eliminated far more rapidly from the human body than is etretinate. It had therefore been suggested that only a short period of contraception would be required after the cessation of long-term therapy with acitretin. However, recent studies have demonstrated the presence of etretinate in the plasma of patients who were treated with acitretin. In this article we provide results from a study in our center and discuss earlier data in light of the recently discovered metabolic pathways for acitretin. Reesterification of acitretin to etretinate, however, results in a loss of the metabolic advantages of acitretin. Because of this situation the recommended contraception period after acitretin therapy has been lengthened to 2 years. PMID- 1460120 TI - Guidelines for optimal use of isotretinoin in acne. AB - Isotretinoin is most effective for patients with acne who fail to respond to other forms of treatment; virtually all patients respond to isotretinoin, 0.5 to 1.0 mg/kg/day. As many as 61% of patients are cured after one course, but 39% require further isotretinoin (16%) or oral antibiotics (23%). The relapse rate can be reduced by the administration of the higher dose of 1 mg/kg/day (thus achieving a significant cumulative dose of > 120 mg/kg), especially to young patients and men with truncal acne and more severe disease. About 85% require a 4 month course, but 15% require longer treatment, with some up to 10 months. There are several reasons for a slow response to treatment, including the presence of macrocomedones, ovarian dysfunction, and as-yet unknown factors. Macrocomedones can be treated with light cautery, ovarian dysfunction with hormonal therapies, and in those persons who have no obvious explanation for slow response, persistence with isotretinoin alone is required. Repeat courses of isotretinoin can also be given. Six years ago most patients treated with isotretinoin had severe acne (60%), but today most patients (60%) have therapy-resistant moderate acne. Isotretinoin is a consideration in such patients to reduce the physical and psychological effects of acne, particularly because there is no simple method to treat acne scars. PMID- 1460121 TI - Side effects of systemic retinoids and their clinical management. AB - The safety profile of oral retinoids appears to be well established, although rare new side effects are occasionally reported. Appropriate patient selection, use of the lowest required dose, and adequate follow-up are significant factors in the prevention of these toxicities. Teratogenicity, which can be avoided by following recommended precautions, is the main adverse effect. PMID- 1460122 TI - Long-term safety of retinoid therapy. AB - The concern about long-term toxicity of oral synthetic retinoids has developed because many patients, especially those with genodermatoses, require lifelong therapy. Several organ systems are at risk, especially the hepatic, skeletal, and cardiovascular systems. Although acute hepatotoxicity is a rare side effect of etretinate and acitretin therapy, prospective studies have not demonstrated chronic liver toxicity. The frequency of bone changes induced by retinoids is difficult to estimate, because this adverse effect is usually asymptomatic and requires x-ray or scintigraphic examination for detection. Atherosclerosis develops in many patients who receive long-term retinoid therapy, but the extent to which the process is aggravated by drug-induced hyperlipidemia is not known. Many patients have now been treated with either etretinate or isotretinoin continuously for as many as 15 years and have not developed any signs of severe chronic toxicity. However, continued intense surveillance is recommended for patients expected to require lifelong therapy. PMID- 1460123 TI - Retinoids for the future: oncology. AB - A major incentive for the development of the synthetic retinoids has been their potential for the treatment and prevention of cancer. Early studies demonstrated that treatment with isotretinoin or etretinate alone could result in the regression of some existing skin cancers. However, even at high doses the response rates were poor. Greater efficacy has been observed with retinoids used in the prevention of cancer of the skin and oral cavity in high-risk patients. The potential for retinoids as chemopreventive agents is being further explored as selected retinoids are being targeted to specific malignancies, such as fenretinide for breast cancer chemoprevention. The effectiveness of tretinoin as a treatment for promyelocytic leukemia has raised enthusiasm for retinoids as cancer therapeutic agents. Furthermore, evidence of synergy between the retinoids and a variety of cytokines as enhances of differentiation chart a bright future for retinoids in oncology. PMID- 1460124 TI - Retinoids in psoriasis and disorders of keratinization. AB - Synthetic retinoids, particularly the aromatic retinoid etretinate (Tigason, Europe; Tegison, United States), have had an established role in the treatment of psoriasis and a variety of ichthyosiform disorders for more than a decade. Isotretinoin (Accutane), which was released at approximately the same time, plays a less important role in these disorders. The mechanism of action of etretinate is still incompletely understood although, like retinoic acid, it is thought to interfere with the terminal differentiation of keratinocytes. The recent detection of nuclear retinoic acid receptors may lead to a unifying theory of retinoid effects and provide the means for more targeted use of this class of compounds. The substantial amount of data on the clinical effectiveness of etretinate was obtained empirically from numerous multicenter trials and individual reports; its indications, dosimetry, pharmacokinetics, and side effects are well established. The main adverse effect associated with etretinate is its teratogenicity (common to all retinoids), which is of particular concern because the lipophilic compound is stored in fat tissue, resulting in an elimination half-life of as many as 120 days. To avoid this problem the much less lipophilic unesterified acid of etretinate, acitretin, has been made available and has now replaced etretinate in many countries. Acitretin represents the active principle of etretinate and has an elimination half-life of 2 days. No significant clinical differences have been observed between these two compounds. Partial in vivo conversion of acitretin into etretinate, however, has been described in some patients. Both compounds are standard treatment for pustular and erythrodermic psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460125 TI - Interaction properties of doubly phosphorylated beta-casein, a major component of the human milk caseins. AB - Doubly phosphorylated beta-casein constitutes nearly 30% of the total human beta caseins and is thus one of the major components of that fraction. The properties and mode of association of doubly phosphorylated beta-casein are therefore important determinants of the structure and function of the human casein micelle. Doubly phosphorylated beta-casein has an absorbency of 6.2 and a partial specific volume of .74. The protein precipitated at room temperature when 10 mM Ca2+ was added but produced a clear solution in 1 M NaCl. Equilibrium dialysis produced an average of 2.06 major Ca(2+)-binding sites at 37 degrees C with a dissociation constant of 12.1 x 10(-4) M. The monomer at 20 degrees C was calculated to have a solvation of 2.1 g of H2O/g of protein and an axial ratio of 6.8, suggesting a prolate ellipsoid of about 11 by 2 nm. At high ionic strength, evidence exists for a spherical structure with a molecular weight of 2.25 x 10(6). This structure would represent a polymer of about 90 monomers with a radius of 14.8 nm and a solvation of 1.93 g of H2O/g of protein. This association behavior is similar to that of other phosphorylated human beta-caseins but differs from the nonphosphorylated form. It changes when both Ca2+ and inorganic orthophosphate are present. PMID- 1460126 TI - B-cell mitogenic activity of slime products produced from slime-forming, encapsulated Lactococcus lactis ssp. cremoris. AB - The mitogenic activities of whole cell lyophylized preparations, cell-wall components, and slime products obtained from Lactococcus lactis ssp. cremoris KVS20 were examined on murine spleen cells. Whole cell lyophylized preparations and slime products significantly (P < .05) stimulated mitogenic responses of the cells. The highest activity was induced by slime products in which the optimal concentration was 116 microg/ml. The significant (P < .05) increase of mitogenic activity induced by slime products occurred at 24 h, and the peak response was obtained 48 h after the stimulation. The activity was much higher in the fraction enriched with B cells than in the fraction enriched with T cells. In addition, slime products induced mitogenic activity to spleen cells of athymic nu/nu mice. The chemical analysis of lipopolysaccharide and the minimal concentration for mitogenic response eliminated the possibility that the activity of slime products may be due to the contamination of lipopolysaccharide. The data demonstrate that slime products are a potent B-cell-dependent mitogen. PMID- 1460129 TI - Season and lactation number effects on milk production and reproduction of dairy cattle in Arizona. AB - Records representing 19,266 Holstein cows from Arizona DHIA data over a 5-yr period were analyzed to determine the effects of season and lactation number on milk production and reproduction. Seasons were winter (December, January, and February), spring (March, April, and May), summer (June, July, and August), and fall (September, October, and November). Traits analyzed by least squares ANOVA were 305-d FCM, complete lactation milk, calving interval, and services per conception. All sources of variation were significant except the interaction between lactation number and season of calving for complete lactation milk. Milk production was depressed for cows calving in summer and fall. First lactation cows had lowest milk production, and highest production occurred in either lactation 4 or 5. Cows calving in spring and summer had reduced reproductive performance, as measured by calving interval and services per conception. First lactation cows had lowest values for both reproductive traits. Previous days dry was negatively related to milk production for spring calvings but was positively related for all other seasons. Cows with higher milk production had reduced reproductive performance. Partial regression coefficients for calving interval and services per conception were 12 d and .25 services per conception per 1000 kg of 305-d FCM, respectively. Despite the negative effects of thermal stress, milk production and fertility in this study were not depressed as severely as in previous research reported from Arizona. Calving schedules may be adjusted to minimize the adverse effect of heat stress. PMID- 1460128 TI - Estrous cyclicity in nonlactating and lactating Holsteins and Jerseys during a Pakistani summer. AB - Data from 36 cows were used in a 2 x 2 factorial arrangement to determine the effects of breed and lactation status on estrous cyclicity during a Pakistani summer (June through October). Cows were selected from a herd of Holsteins and Jerseys imported from the United States 5 yr earlier. Ambient temperatures were highest in June and declined in the ensuing months with the onset of the rainy season. Relative humidity increased in July and August and them remained stable until the end of the study. Although early morning rectal temperatures gradually declined from June through October, late afternoon rectal temperatures were highest in August. Average early morning rectal temperatures were higher in Holsteins than in Jerseys (38.5 vs. 38.3 degrees C). Even though all cows were cyclic throughout the study, as indicated by patterns of progesterone secretion, observed expression of estrus was low (36.8%) and unaffected by breed or lactation status. Average serum progesterone concentrations were lower (2.4 vs. 3.1 ng/ml), and cortisol concentrations were higher (4.1 vs. 3.9 ng/ml), in Holsteins than in Jerseys. Breed by lactation status interactions were significant for lengths of the luteal phase and estrous cycle. Lengths for lactating Holsteins were longer than those of other groups. PMID- 1460127 TI - Effect of high doses of a sustained-release bovine somatotropin on antibody formation in dairy cows. AB - Eighty-two lactating Holstein cows received either one, three, or five concurrent, intramuscular injections of a unit dose (.6 g) of zinc methionyl bST (some-tribove) or five doses of the vehicle. Injections were administered at 14-d intervals from 60 d postpartum until the end of lactation or necropsy. Thirty eight cows continued on the same treatment for a 2nd yr. Blood bST antibodies developed within the first 7 wk of treatment, and the number of cows with anti bST binding generally declined with time. Thirteen out of 59 cows receiving bST developed binding activity > 25% (positives) during the 1st yr. At the .6-g dose level, no binding was detected after wk 15. Seven of the 13 positive cows were among the group randomly selected to continue on study during yr 2. In the 2nd yr, only 2 out of 24 bST-treated cows were positive. Binding activity was associated with the IgG fraction in serum. Binding capacities of antibodies ranged from .625 to 3.04 mg of bST/L, and affinities ranged from 1.14 x 10(8) to 3.14 x 10(8) L/mol. Cows considered to be clinically positive had performance similar to those of their herdmates having binding < 25%. No evidence of a pathologic effect of antibodies existed in treated cows, their calves, or fetuses. The presence of anti-bST antibodies did not affect milk production of the cow or growth of the calves conceived during bST treatment. PMID- 1460130 TI - Lactation curve estimation for use in economic optimization models in the dairy industry. AB - Monthly data on completed lactations were employed to estimate a three-stage least squares lactation curve model for milk production, milk fat content, milk protein content, and body weight change in lactating Holstein cattle. In comparison with previous work on the lactation curve, our study employed an augmented incomplete gamma model of the lactation curve, a simultaneous rather than single equation estimation technique, monthly rather than daily or weekly observations, and a pragmatic treatment of the genetic background of individual cows using sire proof data. In addition to considering genetic and dietary effects on the lactation curve, the model isolates the seasonal effect of calving date and current production month as well as the age of the cow. By allowing for the simultaneous explanation of various measures of cow performance, the model accommodates formulation of diets tailored for individual cows or groups of cows and can be used in profit-maximizing mathematical programming models. Diet, production, and body weight changes are determined simultaneously and are not independent of one another. PMID- 1460131 TI - Effects of feeding diets containing calcium salts of long-chain fatty acids to lactating dairy cows. AB - Four cows were utilized in a 4 x 4 Latin square design to investigate the effects of feeding Ca salts of long-chain fatty acids. Treatments were control diet with 1) no added fat, 2) 3% Ca salts of long-chain fatty acids, 3) 6% Ca salts of long chain fatty acids, and 4) 9% Ca salts of long-chain fatty acids. Cows were fed chopped alfalfa hay, alfalfa haylage, corn silage, and concentrate (15:22:13:50) on a DM basis. Dry matter intake, energy intake, and ruminal fermentation were not altered greatly until Ca salts of long-chain fatty acids constituted 9% of DMI. Digestibilities of DM, OM, ADF, NDF, and hemicellulose were not affected by treatment. Digestibilities of cellulose, soluble residue, total C18 fatty acids, and total fatty acids followed quadratic patterns. Absorption of N was increased linearly when fat was fed, but digestibility of Ca was decreased linearly. Milk production, CP, and SNF were not altered greatly by inclusion of 3 or 6% Ca salts of long-chain fatty acids in the diet, but inclusion of 9% Ca salts of long-chain fatty acids decreased their production. Calcium salts of long-chain fatty acids increased milk fat percentage and production of fat and FCM when fed as 3 or 6% of the dietary DM but decreased yields of milk fat and FCM when fed as 9%. Calcium salts of fatty acids can be fed to provide up to 6% of the dietary DM without deleterious effects on ruminal fermentation and digestibilities of most nutrients. PMID- 1460132 TI - Effects of feeding lactating dairy cows diets containing extruded soybeans and calcium salts of long-chain fatty acids. AB - Four multiparous Holstein cows averaging 36 DIM and fitted with ruminal cannulas were utilized in a 4 x 4 Latin square design to investigate the effects of feeding extruded whole soybeans and Ca salts of long-chain fatty acids. Treatments were diets containing 1) no added fat, 2) 16% extruded whole soybeans, 3) 16% extruded whole soybeans and 3% Ca salts of long-chain fatty acids, and 4) 16% extruded whole soybeans and 6% Ca salts of long-chain fatty acids. Cows were fed for ad libitum intake a diet of alfalfa haylage, corn silage, and concentrate (35:15:50, DM basis). Intakes of DM and energy and production of milk, 4% FCM, fat, CP, and SNF were decreased by feeding extruded whole soybeans and 6% Ca salts of long-chain fatty acids, but differences were small among the other treatments. The weight percentages and yields of C18:0, C18:1, and C18:2 in milk were increased, and most shorter chain fatty acids were decreased, by feeding supplemental fat. Digestibilities of DM, OM, ADF, soluble residue, total C18 fatty acids, and total fatty acids were decreased, but digestibility of hemicellulose was increased by feeding supplemental fat. The largest decrease in digestibilities of most dietary constituents and in energy and N utilization occurred when 16% extruded whole soybeans plus 6% Ca salts of long-chain fatty acids were fed to the cows. Calcium salts of long-chain fatty acids can supply up to 3% of the dietary DM in diets containing 16% extruded whole soybeans without having deleterious effects on most variables measured in this experiment. PMID- 1460133 TI - Influence of method of administration of rapeseed oil in dairy cows. 1. Digestion of nonlipid components. AB - The effects of rapeseed oil supplements on ruminal digestion and total tract digestibility of nutrients were studied in four cows in midlactation, fitted with ruminal cannulas and used in a Latin square design (three periods x three diets). Treatments were basal diet only (control) or 1 kg of rapeseed oil added to a basal diet by continuous infusion or by a single administration via the ruminal cannula. The ratio of forage: concentrate of the basal diet was 68:32 on a DM basis. Total lipid contents were 3.9, 9.4, and 9.4% of DM in control diets and in diets with continuous and single supplementation, respectively. Fat supply decreased total tract OM digestibility (77.0, 72.0, and 74.0% in control diet and in diets with continuous and single supplementation, respectively) because of a depressive effect on fiber digestion. With both oil administration methods, the relative proportion of propionic acid increased and acetic and butyric acids in ruminal fluid decreased. Moreover, continuous infusion of oil increased the proportion of propionate and decreased the proportion of butyrate. When oil was added as a single administration, ammonia N concentration before feeding was lower than when oil was infused continuously. PMID- 1460134 TI - Effects of concentration of dietary phosphorus on amount and route of excretion. AB - Objectives were to determine the effect of dietary concentration of P in DM on routes of excretion of P and to evaluate direct and indirect measures of calculating DM digestibility and P excretion. Twelve lactating Holstein cows were fed 20 kg of DM containing .41% P daily for 4 wk and then were assigned randomly to one of three diets: low (.30%), medium (.41%), or high (.56%) in P for 9 wk. Total collections of excreta (feces and urine) and milk were made during wk 4, 7, 10, and 13. At wk 4, cows excreted 88.2% of P consumed daily: 68.6% of excreted P in feces, 1.0% in urine, and 30.3% secreted in milk. Cows assigned to the low P diet decreased intake by 26.8% and excretion of P in feces by 22.7% in wk 13 compared with wk 4, whereas cows fed the high P diet increased intake by 36.5% and excretion of P in feces by 48.6%. Digestibility of DM was 62.6% when calculated from total collection of feces but only 55.7 or 56.5% when estimated indirectly using Cr or acid detergent lignin as indigestible markers. Apparent excretion of P was less than that estimated using either of the marker techniques (49.7 vs. 59.1 and 58.1 +/- .7 g/d of P) because digestibility of DM was underestimated. A prediction equation was developed for P excretion based on P intake and milk production. PMID- 1460135 TI - Comparison of trace elements in milk of four species. AB - The objective of this study was to compare trace elements in milks of four species. Milk samples of 4 ml or more were obtained from guinea pigs, dairy cattle, horses, and humans. The milks were analyzed for the trace elements Al, B, Ba, Cu, Fe, Li, Mn, Mo, Si, Sr, Ti, and Zn by inductively coupled argon plasma spectroscopy. Zinc ranged from more than 4 ppm in guinea pig milk to less than 2 ppm in mare milk. Strontium was over 1 ppm in the milk of guinea pigs and less than .1 ppm for the human. Iron ranged from over .7 ppm for the guinea pig to less than .2 ppm for the cow. Copper was over .5 ppm in guinea pig milk and only .05 ppm for cow milk. Boron ranged from .59 to .10 ppm, Si from .58 to .16 ppm, Al from .45 to .10 ppm; and Ba from .22 to .08 ppm in milks of the four species studied. Titanium ranged from a trace to .11 ppm. Lithium, Mn, and Mo all were less than .04 ppm. Milk Mn was surprisingly low relative to bodily needs. PMID- 1460136 TI - Effect of yeast culture supplement on production, rumen fermentation, and duodenal nitrogen flow in dairy cows. AB - Six lactating Holstein cows fitted with rumen and T-type duodenal cannulas were used in a crossover design to examine effects of yeast culture supplement on production parameters, rumen fermentation, and flow of N to the duodenum. Treatments were control and control plus 10 g/d of yeast culture. Dry matter intake was greater, and milk production tended to be higher, for cows supplemented with yeast culture, but milk composition was not affected. Rumen pH was not affected by yeast culture, but peak lactic acid concentration decreased from 1.93 to 1.73 mM. Rumen fluid acetate:propionate ratio, dilution rate (percentage per hour), and ammonia N concentration (milligrams per deciliter) were 2.28, .12, and 10.7 and 2.04, .13, and 9.6 for control cows and for cows supplemented with yeast culture, respectively. Although numbers of fiber digesting bacteria were not affected by yeast culture, DM disappearance of wheat straw tended to be higher at 12 and 24 h, and CP and ADF digestibilities were greater. Duodenal NAN flow tended to be higher in cows supplemented with yeast culture because of higher bacterial N flow. Duodenal AA profile and flow of Met were significantly affected by yeast culture supplementation. The results suggest that yeast culture may alter the AA profile of bacterial protein. PMID- 1460137 TI - Effect of microbial inoculant on quality of alfalfa hay baled at high moisture and lamb performance. AB - The effectiveness of a microbial hay inoculant in high moisture alfalfa hay was evaluated. Alfalfa (third cutting) was baled at 72% DM without or with inoculant and at 82% DM without inoculant during yr 1. In yr 2, alfalfa (second cutting) was baled at 75% DM without or with inoculant and at 82% DM without inoculant. Application rate of inoculant was 3.8 L/.98 tonne each year. At this application rate, 90 billion cfu were applied per .98 tonne of forage. Hays were core sampled at 0, 14, 30, and 60 d after baling to determine chemical composition. By d 30, all hays had DM content of 89%. In yr 2, 12 wether lambs were assigned to three treatments in a replicated 3 x 3 Latin square. Treatments were chopped, low moisture hay plus corn; chopped, inoculated high moisture hay plus corn; and chopped, high moisture hay plus corn. All diets contained 63% alfalfa hay, 35% ground corn, and 2% minerals and vitamins. In yr 1, inoculated and low moisture hays were not different in chemical composition but were higher in CP and lower in NDF than high moisture hay. Neither NDF nor CP were different among the three hays in yr 2. Average daily gain was not different on the three diets. The feed to gain ratio was lowest for the inoculated hay, intermediate for the low moisture hay, and highest for the high moisture hay diet. Daily gain and feed to gain ratio were not different for lambs fed the inoculated hay baled at 75% DM compared with lambs fed untreated hay baled at 82% DM. PMID- 1460138 TI - Feeding sequence and strategy effects on ruminal environment and production performance in first lactation cows. AB - Three primiparous cows were assigned randomly to a 4 x 4 incomplete Latin square to evaluate ruminal characteristics (Experiment 1) with the following feeding strategies: strategy A, supplement (protein), forage plus high moisture ear corn (energy), protein; strategy B, energy plus protein, forage, energy plus protein; strategy C, forage plus energy, protein, forage plus energy, protein; and strategy D, forage, energy plus protein, forage, energy plus protein. In Experiment 2, 36 cows were fed diets similar to those in Experiment 1 from wk 4 through 19 postpartum. Cows fed diets according to strategy A had the highest and strategy D the lowest mean ruminal pH. Diurnal variation in ruminal pH was less with cows fed diets using strategies A and B than C and D. Other ruminal parameters were not significantly different. In Experiment 2, cows fed according to strategy B had higher DMI than those fed according to other strategies. Energy and protein fed together and separately from forage, regardless of sequence, increased milk fat percentage compared with protein fed separately. Milk production and protein yield tended to be highest when protein was fed separately, regardless of sequence to forage. Strategic feeding of protein and energy sources in relation to forage influenced some ruminal and production measurements in primiparous cows. PMID- 1460139 TI - Lactation, health, and reproduction of dairy cows receiving daily injectable or sustained-release somatotropin. AB - Seventy-four Holstein cows (26 primiparous) were utilized to compare the efficacy and safety of sustained-release versus daily injectable formulations of recombinant bST. Twenty-four control cows were injected biweekly with oil microsphere; 25 cows were injected biweekly with 350 mg of bST microsphere; and 25 cows were injected daily with 10.3 mg of bST. Injections were initiated between wk 4 and 5 of lactation and continued for 280 d. Administration of bST caused a moderate increase in milk and FCM production and improved the efficiency of feed and energy conversions. Most health-related and reproduction-related variables did not differ among treatment groups. However, incidence of teat and udder disorders and feet and leg problems tended to be higher during the 40-wk injection period for the bST-treated cows than for the control cows. Incidence of GnRH therapy and number of days to first service were higher for daily bST treated cows than for controls. No differences existed between sustained-release and daily bST-treated cows for any parameters monitored. PMID- 1460140 TI - Specific gravity of bovine colostrum immunoglobulins as affected by temperature and colostrum components. AB - The effects of temperature and colostrum components on specific gravity in bovine colostrum were investigated. Thirty-nine first milking colostrum samples were collected from Holstein cows. The samples were assayed for alpha-tocopherol, fat, protein, total solids, and IgG. The concentrations of total solids, total protein, total IgG, and fat in colostrum were 26.6, 12.5, 3.7, and 9.4 g/100 g, respectively. A range of 1.8 to 24.7 micrograms/ml for alpha-tocopherol was measured in the colostrum samples. Specific gravity of the colostrum was measured using a hydrometer in increments of 5 degrees C from 0 to 40 degrees C. Specific gravity explained 76% of the variation in colostral total IgG at a colostrum temperature of 20 degrees C. The regression model was improved only slightly with the addition of protein, fat, and total solids. The model for samples at 20 degrees C was IgG (milligrams per milliliter) = 958 x (specific gravity) - 969. Measurement of specific gravity at variable temperatures necessitated inclusion of temperature in the model for estimation of IgG. Inclusion of the other components of colostrum into the model slightly improved the fit. The regression model for samples at variable temperatures was as follows: IgG (milligrams per milliliter) = 853 x (specific gravity) + .4 x temperature (Celsius degrees) - 866. PMID- 1460141 TI - Genetics of growth, feed intake, and milk yield in Holstein cattle. AB - Heritabilities, genetic and phenotypic correlations among growth, forage consumption, and BW changes of heifers and feed consumption, BW changes, and yields of first lactation cows were estimated. Data were from 1266 Holstein progeny of 74 sires born from 1972 to 1985 at three Agriculture Canada research herds. Heavier heifers at 26 wk consumed more feed from 26 to 34 wk than smaller heifers but gained the same BW. The BW gain and feed consumption heritabilities were .17 and .23, respectively; genetic correlation was .44, and phenotypic correlation was .27. During first lactation, feed intake from 8 to 16 wk and measures of milk yield are very tightly intercorrelated both phenotypically and genetically (.78 to .98). Precalving BW gain and BW at calving were genetically uncorrelated with measures of milk yield (-.09 to +.05). Loss of BW during the first 8 wk of first lactation was moderately heritable (.29) and correlated genetically and phenotypically with measures of milk yield in early lactation (.32 to .39) and feed consumption (.26). From 8 to 16 wk, average BW changes were small and had low heritability and weak phenotypic correlations with measures of milk yield or feed intake. The BW at 26 wk and BW gain from 26 to 34 wk were very poor indicators of early first lactation milk yield. Heifer feed intake was weakly correlated phenotypically (-.07 to .16) but moderately genetically correlated (.17 to .23) with early first lactation milk yield and feed consumption. PMID- 1460142 TI - Milk composition of Majaheim camels. AB - To determine composition, milk samples were obtained at random from camels at two camel rearing areas near Riyadh, Saudi Arabia. Proximate analyses indicated 3.15% fat, 2.81% protein, 4.16% lactose, 10.95% total solids, .15% acidity, .83% ash, and 88.33% water. Mineral composition was (milligrams per gram) 30.03, Ca; 72.48, K; 43.10, Na; .28, Fe; .18, Pb; and 4.50, Mg. Results should contribute to the overall knowledge of camels as a food source, but much still needs to be learned if efficient improvement programs are to be initiated. PMID- 1460143 TI - Evaluation of a nisin-based germicidal formulation on teat skin of live cows. AB - A purified preparation of the nontoxic antimicrobial peptide, nisin (AMBICIN N), was used in the formulation of a germicidal sanitizer suitable for use on cow teats. The germicidal activity of the formulation against mastitis pathogens was measured on teat skin of live cows. The nisin-based formulation gave a mean log reduction of 3.90 against Staphylococcus aureus and 4.22 log reduction against Escherichia coli after exposure for 1 min to the germicide. This activity was comparable with that exhibited by a 1% iodophor teat dip but was significantly greater than that exhibited by the .1 and .5% iodophors and by the .5% chlorhexidine digluconate teat dips. The nisin-based formulation showed little or no potential for skin irritation after multiple application to skin, but iodophor and chlorhexidine digluconate teat dips showed significant potential for skin irritation in comparable studies. PMID- 1460144 TI - Nonprotein nitrogen and protein distribution in the milk of cows. AB - The NPN content of milk represents only 5 to 6% of the total N in milk. However, the significance of this milk N fraction to energy and N metabolism in the dairy cow has not been well characterized. The single largest contributor to the NPN fraction of milk NPN is urea. Urea equilibrates in body water, and blood urea is the primary source of milk urea. The urea in milk can be derived from at least two sources: the end product of digestion and amino acid catabolism. Blood urea N was positively associated with intakes of ruminally degradable and undegradable protein and negatively associated with intake of net energy. Consequently, it might be possible to develop a system to evaluate the dietary protein and energy status of the lactating dairy cow employing milk urea in conjunction with milk true protein. PMID- 1460145 TI - The necessary and sufficient conditions of therapeutic personality change. 1957. PMID- 1460146 TI - Introduction to special section: comorbidity and treatment implications. AB - This article initiates the special section on comorbidity and treatment implications. The presence of comorbidity is recognized, the multiple meanings of comorbidity are mentioned, and an invitation for much-needed research on comorbidity and related treatment is extended. PMID- 1460147 TI - Comorbidity among anxiety disorders: implications for treatment and DSM-IV. AB - Research on comorbidity among psychological disorders is relatively new. Yet, comorbidity data have fundamental significance for classification and treatment. This significance is particularly apparent in the anxiety disorders, which, prior to DSM-III-R, were subsumed under disorders considered more significant (e.g., psychotic and depressive disorders). After considering definitional, methodological, and theoretical issues of comorbidity, data on comorbidity among the anxiety disorders are reviewed as well as data on comorbidity of anxiety disorders with the depressive, personality, and substance use disorders. Treatment implications are presented with preliminary data on the effects of psychosocial treatment of panic disorder on co-morbid generalized anxiety disorder. Implications of comorbidity for research on the nature of psychopathology and the ultimate integration of dimensional and categorical features in our nosology are considered. PMID- 1460148 TI - Comorbidity of schizophrenia and substance abuse: implications for treatment. AB - The problem of substance abuse disorders in schizophrenia patients is reviewed, including the prevalence of co-morbid disorders, assessment, hypothesized mechanisms underlying abuse, and the clinical effects of abuse on the course of illness and cognitive functioning. The principles of treatment for dual-diagnosis schizophrenia patients are outlined, and the limitations of existing interventions are noted. Gaps in current knowledge about the impact of substance abuse on schizophrenia and its treatment are identified, and suggestions are made regarding promising avenues of research in this area. PMID- 1460149 TI - Comorbidity of personality disorders and depression: implications for treatment. AB - This article reviews naturalistic and controlled studies of the impact of comorbidity of personality disorders and depression on response to various forms of treatment. The findings support the common belief that personality disorders are associated with a poorer response to treatment for depression. In contrast, the limited data available suggest that the presence of depression may be a positive prognostic indicator for patients with borderline and antisocial personality disorder. There are insufficient data to draw conclusions regarding the influence of specific types of personality disorders on outcome with specific forms of treatment for depression. More specific assessment of personality disorders, particularly of possible underlying dimensions, is likely to be a more fruitful approach than the currently used categorical approach in identifying effective treatments for patients with personality disorders and depression. PMID- 1460150 TI - Academic underachievement, attention deficits, and aggression: comorbidity and implications for intervention. AB - Although comorbidity with specific learning disabilities is less frequent than commonly reported, externalizing behavior disorders--particularly attention deficit hyperactivity disorder (ADHD)--often overlap with various indices of academic underachievement during childhood. Furthermore, by adolescence, delinquency is clearly associated with school failure. Because the link between behavioral and learning problems often appears before formal schooling, and because the co-morbid problems predict a negative course, early intervention is a necessity. Controlled treatment investigations with youngsters who show these combined problems are rare, and such studies present a host of methodologic and practical problems. I discuss issues surrounding multimodality treatment programs and the potential for long-term interventions to break cycles of school failure and externalizing behavior. PMID- 1460151 TI - Comorbidity and treatment planning: summary and future directions. AB - This summary blends the commentaries from the 6 articles in the special section on comorbidity. Included is a discussion of various definitions of comorbidity, the merits and demerits of a hierarchical diagnostic system, and consideration of the extent, patterning, and nature of comorbidity. Directive comments with reference to future intervention planning mention both assessment (distinguishing overlapping constructs) and treatment (sequencing and treatment manuals) issues. PMID- 1460152 TI - Parenting in context: systemic thinking about parental conflict and its influence on children. AB - Fauber and Long's (1991) overview of research on family therapy with children is a valuable integration of the literatures on the family correlates of and treatments for childhood disorders. Several concerns apply to some of the inferences they draw from risk research, however. Their assertion that various sources of family distress have effects that are mediated primarily through parenting is questionable, as is their suggestion that parenting therefore is the appropriate focus of family treatment. The conceptual issues of reductionism, linearity, holism, and change in defining causality are discussed in questioning these conclusions about etiology and treatment. Other empirical and methodological issues are raised briefly, particularly as they relate to statistical models of direct and indirect influences and to the body of correlational and analogue research on how parental conflict influences children. PMID- 1460153 TI - Problems in families of male Vietnam veterans with posttraumatic stress disorder. AB - Interviews were conducted with a nationally representative sample of 1,200 male Vietnam veterans and the spouses or co-resident partners of 376 of these veterans. The veteran interview contained questions to determine the presence of posttraumatic stress disorder (PTSD) and items tapping family and marital adjustment, parenting problems, and violence. The spouse or partner (S/P) interview assessed the S/P's view of these items, as well as her view of her own mental health, drug, and alcohol problems and behavioral problems of school-aged children living at home. Compared with families of male veterans without current PTSD, families of male veterans with current PTSD showed markedly elevated levels of severe and diffuse problems in marital and family adjustment, in parenting skills, and in violent behavior. Clinical implications of these findings are discussed. PMID- 1460154 TI - Contingent take-home incentive: effects on drug use of methadone maintenance patients. AB - This study examined contingent methadone take-home privileges for effectiveness in reducing on-going supplemental drug use of methadone maintenance patients. Fifty-three new intakes were randomly assigned to begin receiving take-home privileges after 2 consecutive weeks of drug-free urines or to a noncontingent procedure in which take-homes were delivered independently of urine test results. The contingent procedure produced more individuals with at least 4 consecutive weeks of abstinence (32% vs. 8%); 28% of noncontingent subjects also achieved abstinence after shifting to the contingent procedure. Lower baseline rate of drug-free urines was strongly associated with successful outcome, whereas the type of drug abused (cocaine vs. benzodiazepines) did not influence outcomes. Findings support a recommendation for using contingent take-home incentives to motivate abstinence during methadone maintenance treatment. PMID- 1460155 TI - How loss affects anger and alienates potential supporters. AB - The effects of loss of resources and illness symptoms on experienced anger, anger expression, and supporter's anger was studied among patients with severe chronic breathing disorder. Both illness symptoms and resource loss were related to greater anger. Angry feelings, in turn, led to more angry behavior. This angry behavior, in turn, resulted in increased anger of supporters. This process illustrates how chronic stress depletes both personal resources and social resources, making the individual increasingly vulnerable to further stressful experiences, inevitably to be confronted in chronic stress sequences. PMID- 1460156 TI - Measures of affect and nicotine dependence predict differential response to smoking cessation treatments. AB - Smokers (N = 126) were randomly assigned to 6-session smoking cessation treatments consisting of 1 of 2 counseling strategies (skills training or support) and 1 of 2 nicotine exposure strategies (nicotine gum or rapid smoking). Counseling and nicotine strategies were completely crossed; all four combinations resulted in equivalent 1-year abstinence rates. Skills training produced higher initial cessation and more coping responses posttreatment than did support. Rapid smoking, but not nicotine gum, produced tachycardia to the taste of cigarettes posttreatment, consistent with cigarette aversion. The treatments were differentially effective among subpopulations of smokers: Subjects high in pretreatment negative affect responded best to support counseling; those low in pretreatment negative affect responded best to skills training. Self-reports of pretreatment craving predicted response to the nicotine exposure treatments. PMID- 1460157 TI - Family preservation using multisystemic therapy: an effective alternative to incarcerating serious juvenile offenders. AB - Multisystemic therapy (MST) delivered through a community mental health center was compared with usual services delivered by a Department of Youth Services in the treatment of 84 serious juvenile offenders and their multiproblem families. Offenders were assigned randomly to treatment conditions. Pretreatment and posttreatment assessment batteries evaluating family relations, peer relations, symptomatology, social competence, and self-reported delinquency were completed by the youth and a parent, and archival records were searched at 59 weeks postreferral to obtain data on rearrest and incarceration. In comparison with youths who received usual services, youths who received MST had fewer arrests and self-reported offenses and spent an average of 10 fewer weeks incarcerated. In addition, families in the MST condition reported increased family cohesion and decreased youth aggression in peer relations. The relative effectiveness of MST was neither moderated by demographic characteristics nor mediated by psychosocial variables. PMID- 1460158 TI - Comparison of integrated systemic and emotionally focused approaches to couples therapy. AB - This study compared couples receiving two marital therapy approaches and a control group over a 10-week treatment period. Integrated systemic therapy (IST) and an emotionally focused approach (EFT) were both found to be superior to the control and to be equally effective in alleviating marital distress, facilitating conflict resolution and goal attainment, and reducing target complaints at termination. IST couples, however, showed greater maintenance of gains from termination to 4-month follow-up on marital satisfaction and goal attainment. Clients' perceptions of how change occurred and issues related to the use of a team of observers in IST are discussed. PMID- 1460159 TI - Problem solving and suicidality among prison inmates: another look at state versus trait. AB - This research examines the relationships between means-ends problem solving and suicidality among adult male prison inmates in light of new evidence based on inpatient and college student populations suggesting that state, rather than trait, vulnerabilities may be responsible for problem-solving deficits and differences. Using the Means-Ends Problem-Solving Procedure (MEPS) with 93 state prison inmates, we found that among inmates with a history of parasuicide, current suicidality did not affect problem-solving performance. We further found that among nonsuicidal inmates, parasuicide history had no effect on problem solving or affect-suicidality measures. Although these results support new research suggesting that trait problem-solving deficits are not causally linked to suicidality, they raise questions about the potentially unique relationships among suicidality, problem solving, depression, and hopelessness in incarcerated populations. PMID- 1460160 TI - An experimental test of three methods of alcohol risk reduction with young adults. AB - This study tested 3 forms of alcohol risk reduction programming for young adults. Volunteers were randomly assigned to receive a 6-week class and discussion group, a 6-unit self-help manual, or a single 1-hr feedback and advice session with professional staff. Results reveal significant reductions in self-reported drinking at the end of the intervention phase and maintenance of drinking changes throughout a 2-year follow-up period. Comparable drinking reductions were rated across treatments; however, noncompliance with the self-help reading program suggested limited utility. Treatment response was related to subject age, as subjects showed increased drinking during the year they reached legal drinking status. The efficacy of brief motivational interventions and client matching in prevention programs is discussed. PMID- 1460161 TI - Effects of videotaped preparatory information on expectations, anxiety, and psychotherapy outcome. AB - This study examined whether preparation decreases clients' state anxiety and improves therapy outcome and clarified the relations among preparation, expectations, and state anxiety. Ss were 138 adults referred for outpatient psychotherapy. Half of the Ss viewed an 11-min preparatory videotape, while the control group waited an equivalent period before their 1st appointment. Pre-post measures confirmed that Ss who viewed the videotape had more accurate expectations about psychotherapy and lower levels of state anxiety than the control Ss. However, at 2-month follow-up, the prepared group had significantly better outcomes on only 1 of 10 outcome measures. It is suggested that more powerful designs may be necessary to detect long-term effects of preparation and that the short-term benefits demonstrated warrant further study. PMID- 1460162 TI - Increased saliva cotinine concentrations in smokers during rapid weight loss. AB - Although the effect of smoking cessation on weight gain is well-documented, little is known about the effect of weight loss on smoking. We examined the association between saliva cotinine levels and weight loss in a group of 9 obese female smokers during participation in a protein-sparing modified fast (Optifast). For the first 3 months of treatment, subjects consumed only the protein-sparing supplement; for the next 3 months, food was gradually reintroduced. Body mass index and saliva cotinine concentration were assessed at study entry and at 3 and 6 months. A significant weight loss was noted at 3 and 6 months, yet the cotinine level increased significantly over this time. It is unclear whether the cotinine increase is due to metabolic changes or an actual increase in nicotine intake. The results suggest that smoking-related health risks may increase during periods of significant weight loss. PMID- 1460163 TI - D-fenfluramine-induced prolactin and cortisol release in major depression: response to treatment. AB - In order to test the effects of various biological treatments on serotonergic function in depression, twenty-one patients with a diagnosis of major depression underwent neuroendocrine challenge tests before and after treatment with either ECT, fluoxetine or amitriptyline. The serotonin (5-HT) releasing agent d fenfluramine was used as a challenge drug and cortisol (CORT) and prolactin (PRL) plasma levels were monitored over a 5-h period. Overall PRL responses were significantly enhanced following pharmacotherapy irrespective of therapeutic outcome. Effective treatment in each case lowered baseline CORT levels but CORT response to d-fenfluramine remained blunted. Hypercortisolaemia may be involved in the impaired pretreatment PRL response as a strong inverse relationship was established, for the combined studies, between basal CORT plasma concentrations and PRL responses. PMID- 1460164 TI - The familial relation of personality disorders (DSM-II-R) to unipolar major depression. AB - Four hundred and fifty directly interviewed relatives of probands with non psychotic unipolar major depression and 320 directly interviewed relatives of controls were compared by the prevalences of personality disorders (P.D.) as defined by DSM-III-R, in relation to presence or absence of the relatives' affective disorder. Overall, there was only a trend for an increased risk for P.D. in relatives of depressed patients. However, P.D. and unipolar major depression co-occurred more frequently in relatives than expected by chance. It is suggested that this association is mainly due to non-familial factors. Compared with other P.D., the relationship of borderline P.D. to major depression was not substantially stronger. PMID- 1460165 TI - Help-seeking patterns of community residents with depressive symptoms. AB - From a community sample, fifty-five individuals identified as having three or more symptoms of depression were asked if and where they had sought help and how they found or would find treatment. Only 20 subjects (33.9%) reported having sought professional help. No demographic differences were found between help seekers and non-help-seekers. Eighty percent of the help-seekers had seen a mental health professional while 20% had seen a non-psychiatric physician. However, non-psychiatric physicians and friends or personal acquaintances were most frequently cited as the first point of contact for locating treatment. Results suggest that most individuals with a moderate number of depressive symptoms do not seek professional assistance but that, among those who do, a majority is eventually seen by a mental health professional. Virtually all utilize intermediaries other than mental health professionals, however, to locate assistance. The non-psychiatric physician plays a prominent role in locating help for depressed individuals, which suggests the need to educate physicians about appropriate treatment referral. PMID- 1460166 TI - Brofaromine in major depressed patients: a controlled clinical trial versus imipramine and open follow-up of up to one year. AB - In an 8-week controlled double-blind clinical trial with a total of 216 patients Brofaromine was found to be superior to Imipramine with regard to efficacy (Hamilton Depression Scale, von Zerssen self-rating scale, global evaluation) and tolerability (adverse experiences, global evaluation). Mean daily dosages were 93.1 mg/day in the Brofaromine group and 92 mg/day in the Imipramine Group. No tyramine reduced diet had to be observed. Long-term efficacy and tolerability also proved to be good in an open follow-up in the Brofaromine group. PMID- 1460167 TI - Thyroid abnormalities during chronic lithium treatment in Hong Kong Chinese: a controlled study. AB - Fifty Chinese psychiatric patients on chronic lithium treatment and the same number of sex- and age-matched control outpatients were assessed by a thyroidologist and underwent laboratory investigations. Lithium patients had a higher rate of goitres (50% vs 10%, P < 0.0001) and a higher mean TSH level (P < 0.005) than controls. Thyroid antibodies were detected in 7 older manic depressive patients as opposed to 1 control, but not in patients with recurrent unipolar mania. Five patients, but no controls, had single or multiple episodes of hyperthyroidism, which was followed in 2 of them by biochemical hypothyroidism. It is suggested that variations in iodine status, dietary goitrogens, immunogenetic makeup and their complex interactions with chronic lithium treatment may contribute to ethnically different patterns of thyroid abnormalities. PMID- 1460169 TI - Circadian rhythm abnormalities of deep body temperature in depressive disorders. AB - We investigated circadian rhythms of body temperature in 62 inpatients with major depressive episodes, by monitoring the deep body temperature through the abdominal skin every two hours for a consecutive 48-h period. The data were analyzed by both the least-squares method and the maximum entropy spectral analysis (MEM) and were compared with those in 29 normal volunteers who apparently had a regular 24-h sleep-wake schedule. Circadian rhythm phase disturbances in the depressed patients were likely to be manifested in a phase normal or a phase delay pattern rather than in a phase advance pattern. The amplitude of body temperature was significantly smaller and the mesor was higher in the depressed patients than in the normal subjects. Analysis by MEM revealed that the periods of circadian rhythm of body temperature tended to be longer in the depressed patients than in the normal subjects, though there was no significant difference. The power spectral density by MEM was significantly lower, and there were significantly more ultradian rhythm components in the depressed patients than in the normal subjects. These findings suggest that the fundamental rhythm disturbance in depression may be a weakening of the coupling processes between internal pacemakers and an abnormal sensitivity to environmental information. PMID- 1460168 TI - The sleep structure of patients with anxiety disorders in comparison to that of healthy controls and depressive patients under baseline conditions and after cholinergic stimulation. AB - This study investigated sleep EEG during placebo and after cholinergic stimulation with RS 86 in 36 healthy subjects, 34 patients with major depression and 20 patients with anxiety disorders. Cholinergic stimulation with RS 86 led to a decrease of slow wave sleep and REM latency. RS 86 had a more profound impact on REM latency in patients with major depression than in healthy controls and patients with anxiety disorders. Six out of 36 healthy controls, three out of 20 patients with anxiety disorders and 24 of 34 patients with depression displayed sleep onset REM periods after cholinergic stimulation. Also effects on REM density and duration of the first REM period were more pronounced in major depression. Even in those patients with anxiety disorders and a secondary major depression no depression-like sleep abnormalities could be provoked. The results underline the usefulness of the cholinergic REM induction test to differentiate patients with major depression from those with other psychiatric disorders. The results can be interpreted as further evidence for the cholinergic-aminergic imbalance model of depression and for the reciprocal interaction model of nonREM REM regulation. PMID- 1460170 TI - Diurnal variation: reliability of measurement and relationship to typical and atypical symptoms of depression. AB - We used three rating scales to study diurnal variation of mood in 37 patients with major depressive disorder (17 drug-free patients and 20 treatment refractory patients on stable regimens of antidepressant medication). The three rating scales included global self-ratings administered twice a day; an itemized, prospective, observer-rated scale administered twice a day; and the retrospective item on the Hamilton Depression Rating Scale. Z scores and Intraclass Correlation Coefficients demonstrated a poor level of agreement between the itemized, prospective scale and the self-ratings. In addition, stepwise multiple regression analysis and point bi-serial correlation showed no systematic relationship between atypical diurnal variation (i.e., mood worsening in the evening) and atypical depressive symptoms (weight gain, hypersomnia, etc.), or between typical diurnal variation (i.e., mood worsening in the morning) and typical depressive symptoms (weight loss, insomnia, etc.). This lack of relationship was observed in both drug-free and medicated patients using each of the three rating scales. We discuss possible explanations for these negative findings. PMID- 1460171 TI - Severe disturbance occurring during treatment for depression of a bulimic patient with fluoxetine. AB - We report on a 32-year old woman with bulimia nervosa treated with fluoxetine for depression. Fluoxetine is the only drug currently recommended for the treatment of bulimia. The patient became severely disturbed with tension, irritability, self-damage by cutting and violent, intense, suicidal and paranoid ideation qualitatively different to previous symptoms in the course of her illness. Clinical impression was of a striking association between fluoxetine and these symptoms. We suggest caution when using fluoxetine in bulimic patients with depression who have additional impulsive behaviours such as self-cutting, alcohol and/or drug abuse and shop-lifting. PMID- 1460172 TI - Living arrangements, knowledge of health risks, and stress as determinants of health-risk behavior among college students. AB - The association of knowledge of health risks, living arrangements, and perceived stress with health-risk behaviors was examined in a sample of college students included in the Health Promotion and Disease Prevention Supplement of the National Health Interview Survey. Regressions of each health-risk behavior (dependent variable) were performed on the predicted correlates. Although knowledge was not associated with participation in physical activity or smoking, the study found that students who knew more about the harmful effects of alcohol drank less, and those with greater knowledge of health risks practiced fewer risky behaviors. Students living independently were more likely to smoke, and those living in residence halls were less like to do so. Drinking, however, was more common among students living in residence halls or independently than among those living at home. Hall residents engaged in more group physical activity than other students did, but their physical activity was unrelated to health-risk behaviors. Stress was associated with smoking but not with other health practices. The findings suggest that smoking may be less influenced by health knowledge and more associated than drinking is with a response to stress. Drinking appears to be a social activity associated with living among peers and is potentially modifiable by increased knowledge about the effects of alcohol on health. PMID- 1460173 TI - Assessing alcohol problems in college students. AB - Alcohol abuse among college students is prevalent, yet few instruments with sound reliability and validity are available to assess these problems in this population. As part of a large, baseline assessment battery for a prospective study of offspring of alcoholics, the 27-item Young Adult Alcohol Problems Screening Test (YAAPST) was given to 490 freshmen at a large midwestern university; approximately 9 months later, 482 subjects completed the scale again. In addition to asking about such traditional problems as experiencing blackouts and driving while intoxicated, the YAAPST included specific items relating to college experiences (eg, getting into sexual situations that were later regretted, missing classes, and receiving lower grades than usual). The YAAPST was designed to assess these drinking consequences over two different time frames, lifetime and past year, and also to indicate the frequency of occurrence during the past year. Results indicated that the YAAPST is a unidimensional scale with good psychometric properties (good internal consistency and test-retest reliability). Three different approaches were used to demonstrate the validity of the YAAPST. Findings supported criterion validity (with interview-based alcohol abuse/dependence diagnoses as the criterion), concurrent validity (comparing the YAAPST with other drinking measures), and construct validity (correlating the YAAPST with etiologically relevant personality, motivational, and peer influence variables). The YAAPST is a promising screening instrument for alcohol problems in college students. It has excellent psychometric properties and the potential to provide a range of useful information to the clinician or researcher. PMID- 1460174 TI - Fitness profiles and activity patterns of entering college students. AB - Fitness levels of American youth have shown a marked decline in the last decade, according to recent studies. To determine whether such a tendency persists for entering college students, the authors evaluated 115 male and 143 female students for performance on the following fitness-related variables: (1) maximal oxygen consumption (estimated from Astrand cycling protocol), (2) body composition (skin fold techniques), (3) muscle endurance (sit-up protocol), (4) muscle strength (bench-press protocol), and (5) joint flexibility (upper and lower body protocols). Although neither men nor women exhibited high levels of cardiorespiratory fitness, the women in the study showed higher relative levels than their male counterparts. Both groups showed excellent levels of muscle strength (compared with normative standards), but they achieved only an average standard for muscle endurance. Findings of relatively low levels of cardiovascular fitness compared with levels of muscle strength, particularly in men, seem to be a reflection of an inappropriate concentration of physical activity. PMID- 1460175 TI - Recurrent pain in college students. AB - The authors investigated the prevalence of recurrent pain in a college student sample. Of the 1,564 students surveyed, 467 (29%) indicated that they had experienced recurrent pain at an intensity that was mostly in the mild-to moderate range. Students who reported having recurrent pain were significantly older and more depressed than students who did not indicate they suffered from recurrent pain. Pain intensity was positively correlated (r = .14) with depression among the students who reported having recurrent pain. Implications of the findings for future research, treatment, and health promotion efforts are discussed. PMID- 1460176 TI - A liberal arts health promotion course. AB - With a grant from the W. K. Kellogg Foundation, the University of North Carolina at Asheville and the Mountain Area Health Education Center established a campus health promotion program that also trained family practice residents in health promotion skills. The heart of the program was a 3-credit course that emphasized stress management, aerobic conditioning, interpersonal relationship skills, and nutrition. Follow-ups after 2 years revealed that 90% of the students who responded said the course had had some lasting effect on their lives. PMID- 1460177 TI - Surveying University of Arizona students' health. AB - The authors sampled more than 600 University of Arizona students to determine how student attitudes, beliefs, and practices should be considered by healthcare personnel in planning campus health education programs. The survey found that students worried more about diet, exercise, and weight than they did about more serious health problems and that, although generally positive and optimistic, the students frequently felt anxious and overwhelmed. Two thirds of the students were sexually active, 74% of those who were active used various contraceptive methods. More than three quarters of those surveyed indicated they currently drank alcoholic beverages; one quarter of the drinkers said they frequently downed three or more drinks on one occasion, and 44% of the drinkers reported driving while under the influence of alcohol. PMID- 1460178 TI - Alcohol education and treatment: on the use of leverage in the college setting. PMID- 1460179 TI - Gender role strains: one man's awakening. PMID- 1460180 TI - Aging in humans: a continuous 20-year study of physiologic and dietary parameters. AB - The old adage, "You are what you eat," is not always reliable, as demonstrated in this mixed-longitudinal study of men that began in 1969. Mean values of percent body fat, total body potassium (TBK), and total serum cholesterol (SCHOL) did not show changes that correlated with any studied nutrient from repeated 4-day diet records. Mean blood pressure increased with increased body weight as age increased. High-density lipoprotein cholesterol decreased when polyunsaturated fat intake increased. The men had decreased mean height, TBK and increase in percent body fat as age increased. Food energy intake decreased equally from carbohydrates, protein and fat as age increased. Large standard deviations of mean values of measured parameters document heterogeneity of these subjects. A subset of 144 male cohorts was studied serially for 20 years in time-age, cross sectional and longitudinal series. As they aged, height and TBK decreased (p < or = 0.05), percent body fat and blood pressure increased (p < or = 0.04) and SCHOL had no significant change. Intake of all nutrients decreased significantly (p < or = 0.03) longitudinally and with time, showing a time effect. PMID- 1460181 TI - Marginal nutritional status among institutionalized elderly women as compared to those living more independently (Dutch Nutrition Surveillance System). AB - The nutritional status (assessed by anthropometric indices, and biochemical and hematological variables in blood) of three groups of elderly women (aged > or = 65 years) was evaluated within the framework of the Dutch Nutrition Surveillance System. The groups were composed of women living in a nursing home (n = 51), women living in service flats and receiving their dinners from the nursing home kitchen (n = 29), and women living independently (n = 52). Mean blood levels of folate, pyridoxal 5'-phosphate, 25-hydroxyvitamin D, alpha-tocopherol, vitamin C, albumin, selenium and total cholesterol were significantly (p < 0.05) lower among nursing home women. Among these women a biochemical deficiency was frequently found for 25-hydroxyvitamin D (73%), pyridoxal 5'-phosphate (57%), vitamin C (38%), selenium (30%) and folate (28%). These nutritional risks were largely independent of each other. Since folate and pyridoxal 5'-phosphate were associated with several clinicochemical indicators, health status may be an important determining factor for this unfavorable situation. Low 25 hydroxyvitamin D concentrations were associated with limited exposure to ultraviolet radiation and nonusage of vitamin D supplements. We conclude that dietary intake variables are not the only determinants of a marginal nutritional status among nursing home women. Use of foods with a high nutrient density should be encouraged, whereas other preventive measures are needed to improve vitamin D status. PMID- 1460182 TI - Lack of an effect of multivitamins containing vitamin A on serum retinyl esters and liver function tests in healthy women. AB - Two hundred eighty-four female adults (aged 40-70 years) were longitudinally studied to investigate the relationship between dietary supplemental vitamin A and serum biochemical markers of vitamin A toxicity. Serum retinol, retinyl esters, and retinol-binding protein (RBP), alkaline phosphatase and aspartate aminotransferase activities and bile acids were measured at baseline, 1 and 2 years. Fasting serum retinol and retinyl ester concentrations were determined by high-performance liquid chromatography, and dietary and supplemental intake of vitamin A were assessed by 3-day food records. There was no difference in dietary vitamin A intake between supplement users and nonusers. In supplemental users, the mean +/- SEM supplemental vitamin A intake was 952 +/- 81 IU/day (range 250 5000 retinol equivalents/day). Serum retinol, retinyl esters, and RBP concentrations were not different between the two groups during the 2-year period. For each group, serum retinyl esters significantly increased over time (p < 0.03), but the magnitude of the increase was not different between the groups. Serum levels of retinol, retinyl esters, and RBP were not correlated with vitamin A intake or age in either group. Biochemical measures of liver damage (serum alkaline phosphatase and aspartate aminotransferase activities and serum bile acids) were not related to serum retinol, retinyl esters or RBP concentrations, nor were they different between nonusers and users of supplemental vitamin A. This study provides evidence that long-term supplemental vitamin A in doses commonly found in multivitamin supplements does not present a risk for hypervitaminosis A. PMID- 1460183 TI - Effects of dietary magnesium and nickel on growth and bone characteristics in rats. AB - We examined the interaction of dietary magnesium (Mg) and nickel (Ni) on growth and, in particular, the size, composition and mechanical properties of bones in weanling rats. Male rats were fed a diet with 0.3, 1.0 or 2.0 times the recommended concentration of Mg and adequate amounts of other nutrients. After a week, groups fed the low- and high-Mg diets were subdivided and fed the same concentration of Mg plus 0 or 500 mg Ni/kg diet (from Ni chloride) for the remaining 7 weeks. Rats fed low Mg with added Ni grew slowly and had smaller femurs and vertebrae that contained less ash and withstood less force before breaking or compression than did bones of rats fed the low-Mg diet without Ni. However, the breaking stress calculated for femurs from Mg-depleted, Ni supplemented animals was increased. Ni did not produce these effects when added to a diet high in Mg. Compared with high dietary concentrations, the low-Mg intake had little effect unless Ni was added. PMID- 1460184 TI - Zinc status before and after zinc supplementation of eating disorder patients. AB - Reduced food consumption is a major manifestation of zinc (Zn) deficiency. Many manifestations of Zn deficiency are complications of anorexia nervosa and bulimia nervosa. We evaluated serum and 24-hour urinary Zn values in 12 healthy volunteers and 33 eating disorder patients before and after hospitalization which included either Zn supplementation (75 mg Zn/day) or placebo. Bulimics had depressed serum Zn concentrations (p < 0.025). Admission urinary Zn was lower in bulimics (258 +/- 44 micrograms/day), and significantly depressed in anorexics (196 +/- 36 micrograms/day, p < 0.005) vs controls (376 +/- 45 micrograms/day). During hospitalization, serum Zn concentrations increased in all supplemented patients vs no change with placebo. Urinary Zn excretion increased in supplemented bulimics (p < 0.001) and placebo (p < 0.05). Urinary Zn excretion markedly increased in supplemented anorexics (179 +/- 65 to 1052 +/- 242 micrograms/day); however, placebo values fell or remained unacceptably low (admission 208 +/- 48 micrograms/day; discharge 160 +/- 17 micrograms/day). By dietary history, controls consumed the Recommended Dietary Allowance (RDA) for Zn (11.95 +/- 1.25 mg/day); anorexics 6.46 +/- 1.14 mg/day; and bulimics 8.93 +/- 1.29 mg/day. We suggest that Zn deficiency may act as a "sustaining" factor for abnormal eating behavior in certain eating disorder patients. PMID- 1460185 TI - Glucose appearance rate following protein ingestion in normal subjects. AB - The fate of amino acids deaminated following protein ingestion is uncertain. Presumably, the majority of the carbon skeletons of the amino acids are converted into glucose in the liver. In the present study, tritiated glucose dilution tracer studies have been used to determine the effect of a protein meal on the glucose appearance rate in plasma. Five normal male subjects ingested 50 g of protein in the form of cottage cheese. The glucose appearance rate was determined using a constant infusion of 3H-glucose, and compared to the glucose appearance rate following the ingestion of just water in the same subjects over an 8-hour period. The total amount of protein deaminated and converted to urea also was quantitated. Urea production could account for the metabolism of 29.3 g of protein ingested, or 58.5%. Glucose appearing in the circulation as a result of amino acid metabolism determined by tracer methodology was 9.68 +/- 5.7 g. Based on the gluconeogenic potential of cottage cheese (42.3 g of glucose from 50 g of cottage cheese protein), this could only account for at most 43% of protein metabolized, or 23% of the total amount of protein ingested. The fate of the remaining amino acids metabolized remains to be determined. PMID- 1460186 TI - Weight loss, body composition and risk factors for cardiovascular disease in obese children: long-term effects of two treatment strategies. AB - Two treatment strategies were compared to determine their effects on weight loss, body composition and risk factors for cardiovascular disease (CVD) in 32 obese children (relative weight > 120%) aged 6-15 years. Modes of therapy included individual (Group I) or group treatment (Group II). The children were treated for 1 year and observed during the second year. Relative body weight decreased by 16.6% in Group I (p < 0.001) and by 15.8% (p < 0.01) in Group II during the first year; in both groups the lower relative body weight was maintained during the year of observation. No changes were observed in linear growth or lean body mass. Weight reduction was accompanied by increased high-density lipoprotein cholesterol (HDL-C) levels, increased ratio of HDL-C to total cholesterol, and reduced triglyceride concentrations in both groups. Fasting plasma insulin concentrations decreased significantly in Group I. In conclusion, intensive treatment produced significant weight loss, improved serum lipid profile and reduced hyperinsulinemia. These changes, if sustained, may reduce the risk of CVD later in life. PMID- 1460187 TI - The relationship of weight-height indices of obesity to body fat content. AB - The measurement called desirable body weight (DBW) was derived by actuaries to indicate that weight which is associated with the lowest mortality. Percent deviation from DBW has become a standard measure of fatness. A different obesity index, body mass index (BMI), is weight in kilograms divided by the square of height in meters. Many workers consider both measures inferior to the measurement of body fat content (BFC). We compared the three measures of fatness in 40 men aged 18-50 and 48 women aged 21-47, ranging from nonobese to extremely obese. Total BFC was determined by isotope dilution of 3H-labeled water. DBWs used were those listed in the US Air Force Examination Manual of 1971; these approximate the midpoint of the range of medium-frame values in the 1959 Metropolitan Life Insurance Tables, but have the advantage of providing a single value for each height. We found nearly perfect correlation (r = 0.99, p < 0.001) between BMI and percent deviation from DBW in both men and women ranging from 14% below to 305% above DBW. Correlations between percent deviation from DBW and total BFC were extremely high: 0.95 (p < 0.001) for the men and 0.94 (p < 0.001) for the women, essentially the same as correlations between BMI and BFC, which were 0.96 (p < 0.001) for the men and 0.95 (p < 0.001) for the women. It appears that the two technically simple weight-height indices, BMI and percent deviation from DBW, give just as accurate a measurement of fatness as the technically complex measurement of total BFC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460188 TI - Sucrose ingestion following exercise: selected cardiovascular, hormonal, renal, and metabolic effects. AB - Carbohydrates, frequently consumed following exercise for glycogen resynthesis, have been shown to have other systemic effects in resting men. We examined the effects of postexercise sucrose (a disaccharide carbohydrate) ingestion on the renal, cardiovascular, and sympathetic nervous systems. Eight men consumed 1 l of water (W) or 1 l of a 200 g sucrose solution (S) following 1 hour of bicycle exercise at 70% heart rate reserve. Measurements were made during 2 hours of recovery. Heart rate and systolic blood pressure were elevated following S as compared to W (p < 0.009, p < 0.04, respectively). Diastolic blood pressure was lower after S (p < 0.04) and mean blood pressure did not differ between beverages. Plasma and urinary catecholamines decreased similarly after exercise regardless of treatment. After S insulin (p = 0.0019) and glucose (p = 0.0036) were increased but serum aldosterone (p = 0.0083) and potassium (p = 0.0285) responses were lower. No differences were observed for plasma renin activity. Urine volume and kaliuresis were less after S (p = 0.03, p = 0.03). A 24% increase in metabolic rate (p = 0.002) and increased respiratory exchange ratio (p = 0.02) after S were observed. Systemic effects of sucrose ingestion following exercise include cardiovascular, renal, endocrine, and metabolic changes. PMID- 1460189 TI - Use of a modified food frequency questionnaire during pregnancy. AB - The purpose of this study was to examine the usefulness of the self-administered modified Willett food frequency questionnaire (mWFFQ) relative to duplicate 24 hour recall interviews as a dietary assessment tool during pregnancy. Fifty healthy pregnant women living in the upper Midwest were recruited for the study. At gestational weeks 16 and 21 (second trimester) and 30 and 35 (third trimester) the women were interviewed at home; they provided oral responses concerning their food and beverage consumption during the previous 24 hours. At weeks 21 and 35, immediately following the interviews, the women were asked to complete an optically scannable food frequency questionnaire, modified to evaluate daily food consumption during a 2-month time period (mWFFQ). Kilocalories and seven nutrients were computed from all dietary data, based on USDA Handbooks 8 and 456. Regression analyses were performed between nutrient intake from the 24-hour recall averages and the nutrient data generated by the mWFFQ, with the timesters serving as independent time periods. According to our preset criterion, correlation coefficients indicated that the assessment tools were comparable during the third but not the second trimester. During both trials, the mWFFQ provided consistently higher kilocalorie and nutrient values than did the 24-hour recall with the exception of fat intake. Based on our findings we conclude that the mWFFQ is a useful tool for assessing nutrient intake of groups of pregnant women, but that familiarity with the characteristics of the participants and the instrument may be important to data interpretation. PMID- 1460190 TI - Toothpaste flavor-induced asthma. PMID- 1460191 TI - Localization of IgE to lung germinal lymphoid follicles in a patient with allergic bronchopulmonary aspergillosis. PMID- 1460192 TI - Rhinitis and asthma caused by occupational exposure to carob bean flour. PMID- 1460193 TI - The true story of the pilot who was itching to fly. PMID- 1460194 TI - Precision of prick and puncture tests. PMID- 1460195 TI - Intolerance to piroxicam in patients with adverse reactions to nonsteroidal antiinflammatory drugs. AB - To evaluate the tolerance to piroxicam in patients with urticaria induced by analgesic and/or nonsteroidal antiinflammatory drugs (NSAIDs), we carried out a 2 year study in an outpatient clinic. All the patients referred to the clinic for study entered a protocol for evaluation of intolerance to one or more drugs. If patients were allergic to at least two different NSAIDs they were allocated to group A, but if patients were allergic to only one they were considered as having selective intolerance (group B). Either piroxicam or placebo was administered under controlled conditions to both groups. In group A, five out of 18 patients had a positive response to piroxicam. In group B, in all the 25 cases studied a good tolerance to piroxicam was shown. These results indicate that in the group with intolerance to NSAIDs piroxicam induced a positive reaction in 27% of the cases, and that this drug should be administered with caution and with a previous controlled challenge in this type of patient. Piroxicam was well tolerated in the group with selective intolerance, indicating that mechanisms other than interference with the prostaglandin synthesis and release of inflammatory mediators participate in allergic reactions to NSAIDs. PMID- 1460196 TI - Allergenicity of peanut and soybean extracts altered by chemical or thermal denaturation in patients with atopic dermatitis and positive food challenges. AB - Peanuts and soybeans are two of the six most common foods to cause food hypersensitivity reactions in children. We used the serum of 10 patients with atopic dermatitis and positive double-blind, placebo-controlled, food challenges to peanut and two patients with atopic dermatitis and positive double-blind, placebo-controlled, food challenges to soybean to investigate the change in IgE specific and IgG-specific binding to these proteins altered by either chemical or thermal denaturation. We used IgE- and IgG-specific ELISA-inhibition analyses to compare these effects on the crude peanut and crude soy extracts, as well as on the major allergenic fractions of both proteins. Heating the soy proteins at various temperatures and time intervals did not significantly change the IgE- or IgG-specific binding of the soy positive pooled serum. When the peanut proteins were subjected to similar heating experiments, the IgE- and IgG-specific binding did not change. When these same proteins were treated with enzymes in the immobilized digestive enzyme assay system used to mimic human digestion, the binding of IgE to the crude peanut and crude soy extracts was reduced; 100-fold for peanut and 10-fold for soybean. Therefore it appears that thermal denaturation of peanut and soybean protein extracts does not enhance or reduce IgE- and IgG-specific binding activity. Chemical denaturation appears to minimally reduce the binding of these proteins. PMID- 1460197 TI - Complementary DNA cloning and expression in Escherichia coli of Aln g I, the major allergen in pollen of alder (Alnus glutinosa). AB - Previous data showed that the major pollen allergens from trees of the order Fagales, in particular alder, birch, hazel, and hornbeam, are highly interrelated. As only the complete amino acid sequence of Bet v I, the major allergen from birch, has been known, it was of interest to obtain the primary structure of other major allergens of this group, to attribute IgE-binding properties to certain features of the amino acid sequences of those allergens. cDNA was synthesized from alder pollen mRNA, sequence-specifically amplified by polymerase chain reaction and cloned into plasmid bluescript. Comparison of the deduced amino acid sequences of Aln g I and Bet v I revealed a 86.8% homology. The Aln g I encoding cDNA was subcloned into pKK223-3 and expressed in Escherichia coli as a full-length nonfusion protein. The recombinant Aln g I bound IgE from tree pollen-allergic patients and was shown to share IgE-epitopes with Bet v I by inhibition studies with recombinant Bet v I. Computer-aided calculations predicted epitopes in both Aln g I and Bet v I at the same position; the Bet v I molecule was predicted to possess two additional epitopes near the N terminus of the molecule. PMID- 1460198 TI - Increased contraction and inositol phosphate formation of tracheal smooth muscle from hyperresponsive guinea pigs. AB - Tracheal smooth muscle from guinea pigs with documented airway hyperresponsiveness in vivo after multiple antigen challenges produced 30% to 50% greater force than tracheas from control guinea pigs, when stimulated with carbachol, histamine, or leukotriene D4. When cultured smooth muscle cells were incubated with myo[2-3H]inositol, basal uptake of [3H]inositol was similar in cells from normal and hyperresponsive guinea pigs, but when these cells were stimulated with contractile agonists, there was increased uptake of inositol in hyperresponsive cells. Analysis of inositol phosphates by column chromatography and high-performance liquid chromatography revealed the presence of inositol 1,4,5-triphosphate, inositol-1,3,4-trisphosphate, inositol-1,4-bisphosphate, and inositol-1-monophosphate. The release of inositol-1,4,5-triphosphate, inositol 1,4-biphosphate, and inositol-1-monophosphate by smooth muscle cells stimulated with carbachol, leukotriene D4, or histamine was 20% to 40% greater in cells derived from hyperresponsive animals than cells from normal animals. These data demonstrate that the increased muscle contraction of hyperresponsive guinea pig tracheas is associated with increased inositol phosphate metabolism in these cells. Delineating the mechanisms of airway smooth muscle contraction should provide new pharmacologic targets for the inhibition of bronchoconstriction in asthma. PMID- 1460199 TI - Natural history of occupational asthma: relevance of type of agent and other factors in the rate of development of symptoms in affected subjects. AB - It is unknown whether factors such as the nature of the agent, gender, age, atopy, smoking habits, continuous or noncontinuous exposure, and pattern of asthmatic reaction can influence the rate of development of symptoms in subjects with occupational asthma. We compared several clinical and functional parameters among three groups of subjects with occupational asthma caused by Western red cedar (group 1, n = 433), isocyanates (group 2, n = 107), and high molecular weight agents acting through an IgE-mediated mechanism (group 3, n = 121). Survival analysis showed that the three curves relating years of exposure before onset of symptoms to the proportion of subjects without symptoms were significantly different in two respects: (1) almost 40% of subjects in groups 1 and 2 as compared with 20% of subjects in group 3 became symptomatic within 1 year of exposure; (2) after 5 years of exposure, the rate of sensitization was slower for subjects in groups 2 and 3 as compared with those in group 1. Having a nonimmediate reaction at the time of specific inhalation challenges, being continuously exposed and being younger slightly increased the risk at each time point on the curve of developing symptoms in subjects with occupational asthma. These data suggest that the natural history for onset of occupational asthma is different depending on the sensitizing agent. Factors such as age, type of exposure, and pattern of reaction on exposure to the agent also modulate the rate of development of this condition. PMID- 1460200 TI - Identification and characterization of a second major peanut allergen, Ara h II, with use of the sera of patients with atopic dermatitis and positive peanut challenge. AB - Peanuts are frequently a cause of food hypersensitivity reactions in children. Serum from nine patients with atopic dermatitis and a positive double-blind, placebo-controlled, food challenge to peanut were used in the process of identification and purification of the peanut allergens. Identification of a second major peanut allergen was accomplished with use of various biochemical and molecular techniques. Anion exchange chromatography of the crude peanut extract produced several fractions that bound IgE from the serum of the patient pool with positive challenges. By measuring antipeanut specific IgE and by IgE-specific immunoblotting we have identified an allergic component that has two closely migrating bands with a mean molecular weight of 17 kd. Two-dimensional gel electrophoresis of this fraction revealed it to have a mean isoelectric point of 5.2. According to allergen nomenclature of the IUIS Subcommittee for Allergen Nomenclature this allergen is designated, Ara h II (Arachis hypogaea). PMID- 1460201 TI - Evaluation of the Multi-Test device for immediate hypersensitivity skin testing. AB - Test-to-test reproducibility, user variability, and the effect of positive reactions on adjacent negative sites were evaluated for the Multi-Test skin testing device. Twenty-five subjects had skin tests with 24 histamine (1 mg/ml), four glycerosaline controls, and four "dry" controls on two testings 7 days apart. To assess reproducibility from large and smaller histamine reactions and/or their effect on adjacent negative controls, 10 of the 25 subjects were retested once with the same testing format, but histamine at 10 mg/ml was substituted. To determine whether large allergen reactions affect adjacent negative controls differently than histamine reactions, 24 additional patients were retested on arms and back with negative controls adjacent to allergens to which they had prior 3+ to 4+ skin test reactions. Conclusions from 2688 skin tests on 49 patients are as follows: large (mean > 10 mm) histamine reactions reproduced better than smaller (mean < 7 mm) responses--coefficients of variation were 12.3 and 21.4 respectively. A 14% user variability occurred when comparing mean wheal sizes from histamine produced by each nurse and 1.2% when comparing their coefficients of variation. Neither small histamine reactions nor large reactions from histamine and allergens affected adjacent negative controls. We conclude that Multi-Test is a highly reliable skin testing technique that provides good reproducibility of results and low user variability. PMID- 1460202 TI - Comparison of the sensitivity and precision of four skin test devices. AB - Twenty volunteers were skin tested with seven concentrations of histamine phosphate and a glycerosaline control to determine the relative sensitivity and precision of four skin test devices: Greer Pen (GP), Greer DermaPIK (DP), Center Multi-Test (MT), and Morrow Brown needle (MB). The end points of the study were (1) wheal and flare response of each device, with a dose-response curve, (2) the time required to apply each set of eight tests, and (3) the volunteers' subjective assessment of each device. On a different day, 10 of the volunteers were tested to determine the precision of each device. Dose-response curves for half-log dilutions of histamine phosphate were produced with a glycerosaline control. The DP and GP induced wheal and flare responses discernible from that of the glycerosaline control at a lower concentration of histamine phosphate than the MB and MT. The DP took a shorter time to apply eight samples than any other device. The MB was preferred by the most volunteers, but any device tested on the upper half of the back was usually preferred over that tested on the lower half. When 5 mg/ml histamine phosphate was used, coefficients of variation for each device demonstrated that for wheals the precision of the DP, GP, and MT was similar (mean, 21.1%, 23.1%, and 24.5%, respectively). The MB was larger (mean, 59.9%). For flares, the precision of GP and DP was similar (mean, 22.0% and 23.5%, respectively), with the MT and MB larger (mean, 35.5% and 58.2%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460203 TI - American Academy of Allergy and Immunology Training Program Directors' Retreat, Jan. 10-12, 1992. Core curriculum outline. PMID- 1460204 TI - The placebo effect is nothing to sneeze at. PMID- 1460205 TI - The physiology and pathophysiology of the parasympathetic nervous system in nasal disease: an overview. PMID- 1460206 TI - Sensory, parasympathetic, and sympathetic neural influences in the nasal mucosa. AB - Neural mechanisms contribute to many nasal symptoms and syndromes. Sensory nerve stimulation by irritants, mast cell products, and inflammatory mediators leads to sneezing and other systemic reflexes. Parasympathetic reflexes and sensory axon responses combine to increase nasal blood flow, fill venous sinusoids (which thickens the mucosa and reduces nasal patency), induce plasma extravasation, and stimulate glandular secretion of mucous and serous cell products. These putative roles for nerves and neuropeptides in pathologic events open new therapeutic avenues. Anticholinergic agents, peptide neurotransmitter agonists and antagonists, drugs to reduce or modulate sensory or parasympathetic nerve function, potent topically applied glucocorticosteroids, and agents to inactivate inflammatory, secretory, or vascular cells may be of use. Ablation of sensory nerves by topical application of the chili pepper neurotoxin capsaicin has been successful in reducing the symptoms of refractory vasomotor rhinitis. PMID- 1460207 TI - Response of nasal mucosa to histamine or methacholine challenge: use of a quantitative method to examine the modulatory effects of atropine and ipratropium bromide. AB - We have developed a new technique for the direct local administration of test solutions to the nasal mucosa and for quantification of nasal secretory responses. This technique, a variation on several published reports of filter paper use, allows simple and rapid determination of drug effects and facilitates the analysis of ipsilateral and contralateral responses to local challenge of the nasal mucosa. We have used this technique to investigate the secretory responses of the nasal mucosa to methacholine and histamine and to determine the effects of atropine and ipratropium bromide (Atrovent nasal spray) on these secretory responses. PMID- 1460208 TI - Intranasal anticholinergic therapy of rhinorrhea. AB - This article reviews the role of anticholinergic therapy for the rhinorrhea that occurs in various rhinopathies, including irritant reactions, perennial nonallergic rhinitis, viral infection rhinitis, allergic rhinitis, and temperature-induced rhinitis. The use of a topical anticholinergic medication, ipratropium bromide, and its ability to inhibit methacholine and rhinitis-induced hypersecretion is emphasized. Ipratropium bromide appears to be both safe and effective in reducing this troublesome symptom. PMID- 1460209 TI - The use of intranasal anticholinergic agents in the treatment of nonallergic perennial rhinitis. AB - Nonallergic perennial rhinitis is a heterogenous disorder. Although the underlying cause is unknown, there is evidence of an autonomic imbalance with parasympathetic hyperreactivity in affected persons. We review this evidence and the role of ipratropium bromide, an anticholinergic drug with topical activity, in the management of nonallergic perennial rhinitis. The pharmacologic features, safety, and efficacy of ipratropium bromide are reviewed. PMID- 1460210 TI - The anticholinergic treatment of allergic perennial rhinitis. AB - Anticholinergic agents have been used for nonallergic rhinitis expressly to control rhinorrhea. In allergic rhinitis, rhinorrhea can be extremely troublesome and unresponsive to traditional pharmacotherapeutic rhinitis treatments. Anticholinergic agents, through their specific ability to decrease nasal secretory response, should have beneficial effects for allergic rhinitis. In a recent trial ipratropium bromide at concentrations of 0.03% and 0.06% reduced rhinorrhea in allergic subjects without any demonstrable rebound effect. Therefore anticholinergic therapies may be a useful adjunct in controlling the rhinorrhea associated with allergic rhinitis. PMID- 1460212 TI - A point of clarification. PMID- 1460211 TI - A double-blind, placebo-controlled study of the safety and efficacy of ipratropium bromide nasal spray versus placebo in patients with the common cold. AB - Ipratropium bromide (IB) has been found to reduce secretions in the upper respiratory tract; this is accomplished through competitive inhibition of acetylcholine at muscarinic receptors that control rhinorrhea production. This study compared the safety and efficacy of IB with placebo in the symptomatic relief of rhinorrhea in patients with the common cold. Human subjects with symptoms of a common cold, primarily rhinorrhea, were enrolled and treated with either IB (84 micrograms/nostril) or placebo; each was administered as two sprays per nostril, four times a day, for 4 days. Primary efficacy analyses were in clinic measurements of nasal discharge weights over a 3-hour period after administration on days 1 and 2 and assessment of rhinorrhea symptoms by use of a subjective patient-completed visual analog rating scale. IB significantly reduced rhinorrhea an average of 18% over placebo for days 1 and 2 (p = 0.01). Visual analog scale scores showed an average improvement in rhinorrhea of 22% over placebo (p = 0.001). When patients with relatively minor rhinorrhea (baseline weight of nasal discharge < or = 1.0 gm) were excluded, IB produced an average reduction in nasal discharge of 23% over placebo for days 1 and 2 (p = 0.003). PMID- 1460213 TI - How to arrange a shared or part-time residency. PMID- 1460214 TI - Breast cancer in the 1990s. PMID- 1460215 TI - The Breast Cancer Prevention Trial. PMID- 1460216 TI - Early detection of breast cancer. AB - Breast cancer is the most common malignancy in North American women. The incidence rate is increasing by about 2% annually, while the mortality rate has remained stable for 50 years. Screening by physical examination and mammography can decrease the mortality rate in women over 50 by 30%. The screening process is rewarding, but meticulous attention to detail is required in both the physical and mammographic assessment in order to define significant abnormalities. PMID- 1460217 TI - Mammography quality assurance. AB - A poor-quality mammogram is worse than no mammogram. This is particularly true in the screening situation. Quality assurance in mammography is defined as all of the practices that monitor and improve the delivery of mammographic services, including technical performance of the equipment, personnel qualifications, patient interactions, communication, and follow-up. Quality control is the component of quality assurance focusing on the technical performance of mammography equipment. The effectiveness and success of screening mammography depend on consistent production of high-resolution, low-dose mammographic images and their accurate interpretation. This article describes the American College of Radiology's Mammography Accreditation Program as it relates to mammography quality assurance. PMID- 1460218 TI - Physical and mammographic diagnosis of breast cancer and initial work-up. AB - This article briefly reviews breast cancer examination and discusses a variety of physical changes that may occur in the breast suffering from breast cancer. The selected topics include evaluation of breast masses, nipple discharge, nipple changes other than discharge, and a discussion of inflammatory breast cancer and its differentiation from mastitis. Breast cancer appearing as a solitary axillary mass is also discussed. A brief discussion is also undertaken of aspiration cytology, mammographically directed needle localized open biopsies, and mammographically directed or stereotactic needle aspirations for cytology. PMID- 1460219 TI - Psychological impact of the diagnosis of breast cancer on the patient and her family. AB - The diagnosis of breast cancer creates emotional distress for patients as well as family members. This article reviews studies on the psychological adjustment of women and their family members during the diagnosis, hospitalization, and early convalescence from breast surgery. Studies indicate that the diagnostic phase is an extremely stressful time for women, marked by high anxiety, uncertainty, and difficulty making decisions. The hospital phase is especially difficult for spouses, who must juggle work responsibilities with added home responsibilities and also spend time at the hospital supporting their wives. In the convalescent phase, patients and family members need to adjust to changes in family roles, cope with fears about recurrence, and learn to balance the needs of all family members. In order to provide high quality health care to breast cancer patients and their family members, physicians and nurses need to address the emotional as well as the physical aspects of recovery. PMID- 1460220 TI - The in situ carcinomas of the breast. AB - In situ carcinoma of the breast is being diagnosed with greater frequency on breast biopsies. Of the two types of CIS, lobular carcinoma in situ is considered a marker for increased risk of developing breast cancer in either breast, and treatment options are based on different philosophies of careful follow-up vs preventive surgery. Ductal carcinoma in situ is a direct precursor to invasive carcinoma and the variety of treatments available reflect the need to completely excise this lesion. Several trials are now in progress to define the roles of surgery, radiation, and hormonal manipulation in the treatment of both types of CIS. PMID- 1460221 TI - Justification for lumpectomy in the treatment of breast cancer: a commentary on the underutilization of that procedure. PMID- 1460222 TI - Reconstructive options following mastectomy. AB - Reconstructive breast surgery is an option a woman may choose following breast loss due to disease, trauma, or congenital malformation. In choosing breast reconstruction a woman must decide on timing and type of procedure. Recent decisions by the Food and Drug Administration have severely limited the type of reconstructive procedure that can be performed. This article discusses all of the options recently available in order to give information to those treating patients who have had these procedures as well as to be encyclopedic in the event that these techniques become available again. PMID- 1460223 TI - The pathology of breast cancer: staging and prognostic indicators. AB - The natural history of breast cancer is complex and the treatment modalities need to be adjusted to this heterogeneous disease. Several prognostic indicators have been described for breast cancer, including the extent of axillary nodal metastasis, the size of the primary tumor mass, various histopathologic characteristics, estrogen and progesterone receptor content, tumor proliferation index, detection of oncogenes, tumor suppressor genes, loss of heterozygosity, and growth factors. Although no single parameter or combination of parameters can definitively predict the outcome of the disease, combined criteria such as tumor estrogen receptor content, cell proliferative index, and lymph node status are relevant for identifying subsets of breast cancer patients that may require different therapeutic modalities. Detection of oncogenes, tumor suppressor genes, and growth factors need further evaluation to determine their usefulness as prognostic factors. PMID- 1460224 TI - Systemic therapy of breast cancer in early and advanced disease. AB - Despite substantial advances in breast cancer treatment, mortality from this disease remains high. While adjuvant chemo-hormonal therapy has significantly improved survival, breast cancer still claims the lives of more than 45,000 American women each year. This article is a brief review of various modalities used in the management of breast cancer, including adjuvant and neoadjuvant therapy, treatment for advanced disease, dose intensification, and autologous bone marrow transplantation. PMID- 1460225 TI - Psychosocial adjustment of the family to breast cancer: a longitudinal analysis. AB - The purpose of the current study was to assess the impact of the mother's breast cancer on her family during rehabilitation and to determine the processes families use to adjust to the illness over time. Data were obtained from 111 child-rearing mothers with breast cancer on three occasions at four-month intervals using standardized measures of psychosocial adjustment. Results revealed that over time the families experienced significantly lower levels of illness-related demands and the marriages became better adjusted. Levels of depressive mood in the women, however, remained stable. This negative mood negatively affected the quality of the marriage, which, in turn, caused the family to cope less frequently with its problems and to function less well. Results strongly suggest the importance of formally assessing the woman's level of depressed mood and channeling women with stable depressive mood and their families into more intensive support services than those typically provided. Evidence from the current study is that, when not attended to, this depressive mood has sustained, deleterious effects on how well the family does during rehabilitation. PMID- 1460226 TI - Patient and family caregiver reaction to new and recurrent breast cancer. AB - Exploratory data on the mental health (depression), symptoms, and functional status of breast cancer patients and the mental health (depression) and reaction to care of their caregivers are examined in this paper. How both are influenced by new and recurrent disease is also reported. Patients and family caregivers were followed over a six-month period to determine whether new or recurrent disease status altered their reaction to the cancer experience. The data suggest that psychological distress may be more marked in the family member than in the patient. Differences in caregiver reaction were not due to new or recurrent disease status, health status of the patient, or the care process of the caregiver. Future research is needed to isolate the cause of variations in mental health of women and their family caregivers experiencing new or recurrent breast cancer. PMID- 1460227 TI - The politics of breast cancer. PMID- 1460228 TI - Tales from the front: when the doctor gets breast cancer. PMID- 1460229 TI - The implant problem: some personal thoughts. PMID- 1460230 TI - Post-stimulus depression of reflex changes in circular muscle activity in the guinea pig small intestine. AB - The extent and time course of depression of successive reflex responses recorded with intracellular microelectrodes from the circular smooth muscle of the guinea pig small intestine were determined. Two stimuli were used, distension and distortion of the mucosa by compression; these were applied either at the same or at different sites. Excitatory responses oral and inhibitory responses anal to the stimuli were recorded. Post-stimulus depression of both ascending excitatory and descending inhibitory reflexes occurred, but the extent of depression was slightly less for the descending inhibition. A conditioning distension lasting 9 s depressed the excitatory response to a test distension applied 2 s later at the same site by 90%. After 30 s the depression was 50% and test responses were normal if inter-stimulus intervals were increased to 2 min. Increasing the duration of the conditioning stimulus increased the depression. Post-stimulus depression was less for compression stimuli than for distension stimuli and prior mucosal compression had almost no effect on responses to subsequent distension. The post-stimulus depression was greater if conditioning and test stimuli were at the same rather than different sites. For different sites, conditioning stimuli at 15 mm from the recording site (near) depressed responses to stimuli at 30 mm (far) to a greater extent than far stimuli depressed responses to near stimuli. If the conditioning stimulus at 15 mm was maintained until after the far test stimulus was applied, depression of the test response did not occur. It is concluded that the major sites of post-stimulus depression are at the synapses between primary sensory neurons and the first interneurons of reflex pathways, and that post-stimulus depression also occurs at other places in the pathway, presumably at synapses between interneurons or between interneurons and motor neurons. PMID- 1460231 TI - Actions of carotid chemoreceptors on subretrofacial bulbospinal neurons in the cat. AB - Thirty-one barosensitive bulbospinal neurons were recorded from the subretrofacial (SRF) nucleus in eight chloralose-anaesthetised, paralysed cats. Close arterial injections of CO2-saturated saline were used to stimulate carotid body chemoreceptors. Seven neurons were abruptly excited and six neurons abruptly inhibited by chemoreceptor stimuli: these were primary responses, independent of changes in blood pressure or central respiratory drive (monitored from the phrenic nerve). A further eight neurons responded only indirectly to chemoreceptor stimuli, showing enhanced modulation of their activity coupled to the enhanced central respiratory drive. The distinction between primary and secondary responses was shown more clearly when central respiratory drive was inhibited by superior laryngeal nerve stimulation. The remaining ten neurons showed no clear response to chemoreceptor stimuli. SRF bulbospinal neurons thus show the same range of responses to chemoreceptor stimuli as the sympathetic neurons they are believed to drive. PMID- 1460232 TI - The amplitude and periodicity of synchronized renal sympathetic nerve discharges in anesthetized cats: differential effect of baroreceptor activity. AB - We applied a computerized peak detection algorithm to recordings of synchronized sympathetic nerve discharges from anesthetized cats to retrieve information about the characteristics of renal nerve activity (RNA) during changes in baroreceptor activity. The algorithm scanned the series of RNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RNA peak had been detected, its corresponding amplitude, width and peak-to-peak interval were calculated. The peak-to-peak interval periodicity showed two modes of synchronized discharge, one between 200-500 ms accounting for 47% of intervals, and a higher 20-180 ms frequency (49% of intervals). Baroreceptor stimulation decreased the occurrence of the high frequencies while increasing the probability of the lower frequency components. The overall occurrence of synchronized peaks per second fell linearly to zero with increases in blood pressure. The peak amplitude of RNA was unimodally distributed and was not affected by baroreceptor stimulation until an increase in mean arterial pressure reached a threshold (mean 142 +/- 5 mmHg) whereupon it fell quickly to zero. Sino-aortic vagal denervation did not affect the distribution of peak height. The width of synchronized discharges was also unimodal, mean 82 +/- 1 ms, and was almost unchanged during baroreflex stimulation acting in parallel with changes in the peak amplitude and decreasing at high blood pressures. Sino-aortic vagal denervation did not affect the synchronized width. There was no relationship between the periodicity and amplitude or width of synchronized discharges under all conditions. The results indicate that the periodicity and amplitude of renal synchronized discharges appear to be independent of each other and are differentially affected by baroreceptor input. PMID- 1460233 TI - Effect of asphyxia on the frequency and amplitude modulation of synchronized renal nerve activity in the cat. AB - A computerized peak detection algorithm was used to retrieve new information about changes in the characteristics of renal nerve activity (RNA) with asphyxia in anesthetized cats. The algorithm scanned the series of RNA voltages for significant increases followed by significant decreases in a small cluster of voltage values. Once each synchronized RNA peak had been detected, its corresponding amplitude, width, and peak-to-peak interval were calculated. The peak-to-peak interval showed two rhythms of synchronized discharge: one between 200-500 ms accounting for 38 +/- 3% of intervals and a higher 20-180 ms frequency (52 +/- 5% of intervals). Asphyxia did not change the periodicity distribution despite increases in arterial pressure. The peak amplitude of RNA, reflecting the number of active fibers, was unimodally distributed and was increased 39 +/- 9% with asphyxia. The shape of the distribution was unchanged. The width of the synchronized activity was also unimodally distributed, mean 79 +/- 3 ms, and increased by asphyxia to 99 +/- 5 ms. The results indicate that the control of the periodicity and amplitude of synchronized discharge appear to be independent and are differentially affected by chemoreceptor input. PMID- 1460234 TI - Sympathetic and sensory neurons projecting into the cervical sympathetic trunk in the chicken. AB - The cell bodies of the sensory and sympathetic pre- and postganglionic neurons projecting into the cervical sympathetic trunk were retrogradely labeled with horseradish peroxidase in the chicken. Preganglionic neurons were located in the spinal segments T1-T6 (maximum T2), postganglionic neurons in the paravertebral ganglia T1-T3 (maximum T1) and sensory neurons in the dorsal root ganglia T1-T4 (maximum T1). Labeled preganglionic neurons were widely distributed across the intermediate gray matter and lateral funiculus, but the majority of them were located in the intermediomedial area dorsolateral to the central canal. The short and long axis diameters of labeled preganglionic neurons in this area decreased caudally. From the data of the present study, it is estimated that about 4190 preganglionic, about 450 postganglionic and about 390 sensory neurons project into the cervical sympathetic trunk cranial to the paravertebral ganglion T1 in the chicken. PMID- 1460235 TI - Ultrastructural localization of angiotensin II-like immunoreactivity (A II-LI) in the vegetative networks of the spinal cord of the guinea pig. AB - The localization of angiotensin II-like immunoreactivity (A II-LI) has been studied at an ultrastructural level in the thoracic and sacral spinal cord vegetative regions of male and female guinea pigs. Most of the AII-LI structures are axon terminals and fibers localized in both vegetative networks which connect bilaterally and cranio-caudally and/or caudo-cranially the preganglionic vegetative nuclei in the thoracic and sacral spinal cord intermediate zone. The A II-LI product is localized predominantly in large granular and small vesicles of axon terminals and varicosites which form axo-somatic, axo-dendritic and axo axonal synapses. Occasionally A II-LI is observed over cysterns of the endoplasmatic reticulum and throughout the cytoplasm of astrocytes which are neighbouring on blood vessels and are in contact with neuronal processi. Immunoreactive terminals are observed in direct contacts with endothelial cells too. These observations confirm recently described light-microscopic localization of Ang II-LI in the studied spinal cord areas, as well as its suggested role as transmitter and/or modulator of the neuronal function and regulatory role over the cardiovascular function and blood circulation. PMID- 1460236 TI - Seasonal variations in acetylcholine content and the levels of cholinergic enzymes in the alimentary tract and heart of Rana esculenta L. AB - The acetylcholine (ACh) content and the relative levels of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) were measured in the stomach and intestinal musculature and in the heart muscles of frogs (Rana esculenta L.) during hibernation (January-stage 1), low activity (April-stage 2) and high activity period (July-stage 3). The ACh content doubled in the stomach from stage 1 to 2, then little change occurred. In the intestine, the ACh content changed little during the stages, while slightly decreased levels were found in the heart from stage 1 to 3. A significant increase in the level of ACh was found in the brain during the entire period. The level of ChAT increased in all tissue samples during the time. The AChE level was not significantly different during the stages in the stomach and intestine. In the heart, a 2.5 fold increase was measured in April compared with January, followed by a sharp decrease to half of the April level by July. In the brain, the activity of this enzyme increased continuously from January to July. The results show that these important cholinergic parameters change differentially in different organs in this poikilotherm animal during the year, presumably resulting in a fine control of the viscera, probably in cooperation with other autonomic transmitter systems. PMID- 1460237 TI - Responses of single units in the midline medulla to stimulation of the rostral ventrolateral medulla. AB - Single units in the midline medulla were characterized as sympathoexcitatory (SE), sympathoinhibitory (SI) or serotonin (5-HT) neurons. Post-stimulatory changes in the firing patterns of sympathoexcitatory, sympathoinhibitory and 5-HT units were observed during single shock stimulation of the pressor area of the rostral ventrolateral medulla (RVLM). Excitation, inhibition, or no change in cell firing patterns were observed for each cell type, but each cell showed only one type of response to stimulation. No midline neurons were antidromically activated by stimulation of the rostral ventrolateral medulla. These results are discussed in relation to neuronal pathways between the RVLM and the midline medulla involved in the generation of sympathetic activity. PMID- 1460238 TI - Diabetic photographic eye screening using a mobile unit in Tayside, Scotland. AB - Early detection and hospital referral of patients with diabetic changes (retinopathy) is essential if laser photocoagulation is to be effective. The British Diabetic Association (BDA) have therefore funded several diabetic mobile eye screening units and donated them to areas throughout the country, the aim being to screen patients for diabetic retinopathy in those areas. This article describes the use and findings of such a unit in the Tayside area. PMID- 1460239 TI - Use of unsharp masks with high-contrast retinal nerve fibre layer photographs. AB - Retinal nerve fibre layer (RNFL) photography is an established and integral tool in the management of ocular hypertensives and glaucoma suspects, and in assessing the management of glaucoma in an ophthalmic practice. When RNFL negatives are viewed for analysis, high-contrast negatives yield the most information. When positive prints are subsequently requested, the RNFL negatives are difficult to print. The use of an unsharp mask facilitates the transfer of all the high contrast negative density range to the print. The use of an unsharp mask has been simplified so that it is quick and efficient and can be adapted for high-contrast negatives other than RNFL images. PMID- 1460240 TI - The use of video in assessing and illustrating abnormal eye movements in young children. AB - Eye movement studies can be useful in neuro-ophthalmological investigations of infants and young children. In our laboratory we use a combination of an electro oculogram and video to record eye movements. A composite video image is created consisting of an image of the electro-oculographic eye movement trace superimposed on an image of the patient's eyes and face. This permits the qualitative clinical appearance of the case to be illustrated simultaneously with the quantitative eye movement trace. PMID- 1460241 TI - Some simplified methods for the photography of equipment and apparatus. AB - A simplified approach to the photography of equipment and apparatus is described. A number of examples are shown of the use of portable flash equipment, fluorescent light boxes and 'north-light' (daylight from North-facing windows), as light sources. PMID- 1460242 TI - Blast: injury patterns and their recording. AB - Exposure to explosive blast results in a variety of injuries dependent on the degree of blast loading, the relative contribution of secondary fragments and the interaction of a casualty with the surroundings. The internal and more covert injuries peculiar to blast are easily overlooked in the haste to treat the obvious external wounds which are usually much more dramatic. This paper describes the pathogenesis of blast injury and suggests how best it may be recorded. PMID- 1460243 TI - Translocation of aged cyclodiene insecticide residues from soil into forage crops and pastures at various growth stages under field conditions. AB - Field trials were conducted to measure translocation of pesticides by summer and winter forage/pasture species from soil containing aged residues of heptachlor and, to a lesser extent, dieldrin. Substantial amounts of heptachlor epoxide, and lesser amounts of gamma-chlordane were translocated to plants from contaminated soil. Residue levels varied with crop species and stage of plant development. In summer crops residues were higher in soybean > cowpeas > lab-lab > Sorghum > millet > sweet saccaline at the grazing and mature stages. Compared to glasshouse studies undertaken previously, residues in crops grown under field conditions were much lower. This apparently reflects the lower soil moisture levels and the reduced rates of translocation. Heptachlor residues in winter crops were highest in Saia oats > Berseem clover > Haifa clover > Cassia oats > Tetila ryegrass > Schooner barley > Shaftal clover > Hunter river lucerne at the grazing stage. There were no detectable levels in barley and oats at the mature stage. No dieldrin residues were translocated into the various crop species. PMID- 1460244 TI - Comparative metabolism of phenanthrene in the rat and guinea pig. AB - In the present study the biotransformation of phenanthrene in the rat and guinea pig was investigated. 14C-labelled phenanthrene was administered by gavage in corn oil to Sprague-Dawley rats (10 mg/kg b.w./day) and guinea pigs (10 mg/kg b.w./day). Urine and feces were separately collected for the determination of the radioactivity content, and pooled urine was used for the analysis of metabolites. Phenanthrene was metabolized by the rat and guinea pig to free hydroxylated phenanthrenes and their conjugates. The percentages of conjugates, expressed as the total urinary radioactivity, were 39% glucuronides, 24% sulfates and 18% cysteinylglycine for rats; and 39% glucuronides, 23% sulfates and 28% cysteinylglycine for guinea pigs. Enzymatic hydrolysis of glucuronides and sulfates resulted in the formation of free 1,2-, 3,4- and 9,10-dihydrodiols of phenanthrene and 1-, 2-, 3-, and 4-hydroxyphenanthrene in both species. PMID- 1460245 TI - Hexachlorophene induced alterations in brain carbohydrate metabolism of Wistar rat. AB - Effect of repeated oral administration of hexachlorophene (HCP) on glycolytic and oxidative pathways was studied in the rat brain. The rats were divided into three batches of six in each batch. The first batch was treated with paralytic dose (60 mg.kg-1.day-1) of HCP for 7 days. The second batch of animals was treated with sublethal dose (18 mg.kg-1.day-1) for 7 days. The third batch of animals was served as the age matched controls which received vehicle (corn oil) only. The glycolytic and oxidative metabolism of carbohydrates was significantly inhibited in the brain of rat during HCP treatment and the inhibition was more pronounced in paralytic dose treatment as compared to sublethal dose treatment. The inhibition of NADP-isocitrate dehydrogenase coupled with glucose 6-phosphate dehydrogenase indicates reduced generation of NADPH2 and pentoses for the synthesis of fatty acids and nucleotides. PMID- 1460246 TI - Cholecystokinin, a satiety signal in newborn infants? AB - This study was undertaken in order to describe circulating glucose and cholecystokinin (CCK) concentrations in relation to the spontaneous feeding behavior of the human newborn infant. Eighty-three, healthy, 3-days-old infants were studied in connection with breast feeding. Blood samples from the infants were cross-sectionally collected before feeding, 5 and 10 min after the start of sucking, and after the infants had sucked ad libitum. Before feeding, the infants presented a typical "hunger behavior", which changed in connection with breast feeding into a pattern associated with satiety. A significant increase in the plasma CCK concentration was found, 5 min (P = 0.004) and 10 min (P = 0.02) after the start of sucking, as well as after feeding (P = 0.04). Furthermore, a positive correlation between the CCK concentration and the volume of ingested milk was found 10 min after the start of sucking, when 91% of of the volume of milk had been ingested; Rs = 0.51, n = 19, P < 0.02. However, no change was found in the glucose concentration in connection with breast feeding. It is concluded that CCK may be important as a satiety factor in the regulation of food intake in the newborn infant. PMID- 1460247 TI - The effect of 10% O2 on the continuous breathing induced by O2 or O2 plus cord occlusion in the fetal sheep. AB - Although the administration of 100% O2 alone or combined with umbilical cord occlusion induces continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990a), the individual contribution of O2 and cord occlusion to the response have not been determined. We hypothesized that if O2 is an important factor in the induction of continuous breathing, administration of O2 low enough (10%) to bring fetal arterial PO2 to about 20 torr while the fetus is breathing continuously should reverse these changes. Thus we subjected 12 chronically instrumented fetal sheep to 10% O2 for 10 minutes after the establishment of continuous breathing by O2 (4 fetuses; 137 +/- 1 days) or by O2 plus umbilical cord occlusion (8 fetuses; 134 +/- 1 days). Arterial PO2 decreased from about 250 torr to 20 torr during 10% O2. This induced a significant decrease in breathing output (EMGdi x f) related primarily to a decrease in frequency (f). In 3/5 experiments in 4 fetuses, with O2 alone, apnoea developed within 4 +/- 0.6 min; in 12/13 experiments in 8 fetuses, with added cord occlusion it developed at 5 +/- 0.6 min. With the decrease in PaO2, electrocortical activity (ECoG) switched from low to high-voltage within 6 minutes in 5/5 experiments (O2 alone) and in 11/13 (O2 plus cord occlusion). The findings suggest that umbilical cord occlusion alone is not sufficient to maintain breathing continuously and an increased PaO2 is needed. We speculate that in the fetus there is a vital link between PaO2, breathing and ECoG with low PaO2 inhibiting and high PaO2 favouring breathing and arousal. PMID- 1460248 TI - Fetal breathing is not initiated after cord occlusion in the unanaesthetized fetal lamb in utero. AB - We investigated the role of cord occlusion in the initiation of breathing at birth using an extracorporeal membrane oxygenator system to control fetal blood gases independently of the placenta in 12 chronically instrumented fetal lambs. In group IA (n = 9; exp = 12) PaCO2 was kept constant (5.62 +/- 0.21 to 5.70 +/- 0.23 kPa) during cord occlusion. Group IB (n = 7; exp = 8) were cord occlusion experiments from group IA in which no fetal breathing movements had occurred; CO2 flow to the membrane was increased and fetal PaCO2 rose significantly (5.45 +/- 0.24 to 8.27 +/- 0.56 kPa). In group II (n = 7; exp = 12) PaCO2 was allowed to increase from 5.98 +/- 0.24 kPa to 8.09 +/- 0.48 kPa after cord occlusion. Within 5 min of cord occlusion, FBM did not occur in 11 out of 12 experiments in group IA or in 11 out of 12 experiments in group II. In contrast in group IB breathing did occur in 5 out of 8 experiments. When they occurred, fetal breathing movements were always associated with low voltage electrocortical activity. Our results do not support the hypothesis that the initiation of breathing within 5 minutes of birth is dependent on an inhibitory factor of placental origin. Furthermore these data suggest an association between the presence of breathing and a substantial rise in PaCO2. PMID- 1460249 TI - Effects of hyperoxia on the metabolic response to cold of the newborn rat. AB - We asked what effects hyperoxia may have on the metabolic response to cold of the newborn rat. Whole body gaseous metabolism (VO2 and VCO2) was measured in 2-day old rats by open flow respirometry at ambient temperatures (Tamb) between 40 and 20 degrees C, changed at a rate of 0.5 degrees C/min during normoxia and hyperoxia (100% O2 breathing). In normoxia, the thermoneutral range was very narrow, at Tamb = 33-35 degrees C. A decrease in Tamb at first stimulated VO2; a further drop in Tamb below 28 degrees C reduced metabolic rate. The metabolic response to cold was not sufficient to maintain body temperature (Tb). In hyperoxia average values of VO2 were above the normoxic values at all Tamb, but the difference was mostly apparent at low Tamb; at 20 degrees C, hyperoxic VO2 averaged 73% more than in normoxia. This metabolic increase determined a significant but small rise of Tb. We conclude that in the 2-days-old rat hyperoxia has a stimulatory effect on metabolism which is Tamb-dependent, being much more apparent in the cold. This supports the concept that the normoxic VO2 of the newborn is limited by the supply of O2. However, the fact that in the cold, even in hyperoxia, VO2 did not reach very high values, and Tb was not maintained, suggests that not only O2 availability, but also the rate of O2 utilization limits the aerobic metabolic response of the newborn. PMID- 1460250 TI - The vit gene maps to the mi (microphthalmia) locus of the laboratory mouse. AB - The murine model for human vitiligo (the vit/vit mouse) develops progressive depigmentation of the pelage, skin, and eyes. The vit gene is inherited as an autosomal recessive. We have used classical breeding and isozyme marker analysis to map this vit gene that produces a vitiligo-like condition in the mouse. Crossbreeding the C57BL/6J-vit/vit mice with C57BL/6J mice carrying the Miwh and/or miws alleles at the microphthalmia locus resulted in mutant phenotypes, demonstrating absence of complementation. When vit is heterozygous with the Miwh allele, a "blotched" pigment pattern results. When it is heterozygous with the miws allele, a novel expression of the vitiliginous phenotype results. Further mating analysis of these crossbred populations demonstrates allelic inheritance between vit and the alleles at the microphthalmia locus. Other breeding studies using alleles at the agouti, belted, brown, dominant spotting, extension, mahogany, patch, and piebald loci did not demonstrate pigmentation explainable by allelic inheritance with the vit gene. Also, vit was tested for linkage with isozyme markers located on chromosomes 1, 4, 5, 7, 9, and 11, and results were negative. Therefore, the vit (vitiligo) gene of the laboratory mouse has been mapped to the mi (microphthalmia) locus on chromosome 6. The gene properly should be designated as mivit. PMID- 1460251 TI - Selection for canalization at extra dorsocentral and scutellar bristles in Drosophila melanogaster. AB - Direct artificial selection for a specific pattern, in the number and position of extra bristles, was carried out in a wild-type population of Drosophila melanogaster to canalize (estimated by probit width) the selected phenotypes. From the same population, independent lines were selected for extra dorsocentral bristles (lines D3 and D4) and for extra scutellar bristles (lines E2, E3, and E4). Differences at canalization between both dorsocentral and scutellar systems were detected. Results fit an independent control hypothesis for canalization, at two symmetrical extra bristles, in the main regions in which extra bristles appear. PMID- 1460252 TI - Identification of an autosome to X chromosome translocation in the domestic cow. AB - Chromosomes were harvested from two fibroblast lines derived from a phenotypically normal cow and her albino daughter, both known to be heterozygous for an X/autosome translocation. QFH-banding after early BrdU incorporation identified the translocated autosomal material as chromosome 23 bands 13-25, and revealed that the centromeric portion of the translocated chromosome 23 had been retained. Fluorescent in situ hybridization of a BoLA Class I cDNA probe to the normal chromosome 23 and to the translocated autosomal material confirmed the identity of the translocation, and allowed a more precise sublocalization of the MHC in cattle than that previously reported. PMID- 1460253 TI - Health Policy Commission report alarming. PMID- 1460254 TI - Selected demographic changes in medicine. PMID- 1460255 TI - State funds needed for proper care of Central State patients. PMID- 1460256 TI - Woman physician sees need for mentors. Interview by Bob Carlson. PMID- 1460257 TI - Commission studies Indiana health care delivery. PMID- 1460258 TI - Doctor fills her life with favorite things. PMID- 1460259 TI - Cardiac transplantation at IU Medical Center. PMID- 1460260 TI - Maternal mortality in Indiana: a report of maternal deaths in 1990. PMID- 1460261 TI - From the museum. PMID- 1460262 TI - Blepharitis. AB - Blepharitis is an acute or chronic inflammatory process involving the eyelids that is frequently associated with conjunctivitis. In its many clinical forms, blepharitis is one of the most common diseases seen by ophthalmologists; yet it remains a diagnostic and therapeutic challenge. This article reviews the clinical presentation, classification, diagnosis, etiology and pathogenesis, and treatment of blepharitis. PMID- 1460263 TI - Infectious conjunctivitis. AB - This article is designed to aid the clinician in the diagnosis of bacterial and viral conjunctivitis by evaluating a wide variety of infectious causes of conjunctivitis. The work-up, including techniques of examination and pertinent laboratory studies, is discussed. Clinical features of each type are covered at length and specific therapy for each is included. PMID- 1460264 TI - Conjunctivitis of the newborn. AB - Infectious conjunctivitis of the newborn is caused by a wide variety of microorganisms. The ocular findings may be part of a widespread systemic infection. Clinical presentations are not diagnostic of the cause, and a microbiologic work-up with cytology, cultures, and microbial sensitivities is mandatory. The selection of specific antimicrobial therapy is based on the findings of laboratory studies. Prophylaxis with silver nitrate solution, 1.0% tetracycline, or 0.05% erythromycin ointment is effective for the prevention of gonococcal and chlamydial conjunctivitis in the newborn. PMID- 1460265 TI - Bacterial keratitis. AB - Bacterial keratitis is an urgent problem requiring recognition, laboratory evaluation, and administration of therapy. The recognized risk factors are outlined. The likely bacterial causes may vary among regions of the country over a period of time. Topical fortified antibiotic eyedrops are the mainstay of therapy; indications for other modalities of therapy are discussed. Specific antibiotic regimens are offered. PMID- 1460266 TI - Fungal keratitis. AB - As Jones has emphasized, the successful management of microbial keratitis, fungal or otherwise, necessitates five steps: (1) clinical suspicion and clinical diagnosis; (2) performing the proper laboratory procedures; (3) initiating antimicrobial therapy based on the results of laboratory studies; (4) modifying the initial therapy based on the clinical response; and (5) deciding correctly when and how to terminate therapy. Keratomycosis poses special diagnostic and therapeutic challenges for ophthalmologists because of its low incidence, and its resistance to treatment, because of the lack of antifungal agents with good penetration into the eye, and because of the difficulties in obtaining meaningful in vitro drug susceptibility results for fungal isolates. We believe, however, that ophthalmologists are now diagnosing keratomycosis earlier and treating it more effectively. PMID- 1460267 TI - Infectious endophthalmitis. AB - The internist or family medicine consultant can have an important role in the management of endophthalmitis. Even though intraocular antimicrobial therapy is the most effective method of treatment, the consultant can assist in the selection of systemic antibiotic agents and in the monitoring of systemic side effects of the treatment. In addition, the consultant can be called on to evaluate patients with endogenous endophthalmitis for systemic involvement. The joint efforts of the ophthalmologist and consultant should allow optimal treatment in an attempt to improve the visual prognosis for these devastating ocular infections. PMID- 1460268 TI - Viral infections of the choroid and retina. AB - DNA (herpes viruses) and RNA (rubella, rubeola) group viruses are recognized causes of viral retinitis. Severe damage is often the result, not only because the viruses have a cytologic effect but also because the antigens may cause immune complex deposition that results in vasculitis. Most of the viral retinitides are associated with systemic disease; immune-compromised individuals are more susceptible than healthy individuals. A distinct clinical entity, acute retinal necrosis, affects the eye only in healthy individuals and is associated with the herpes family of viruses. PMID- 1460269 TI - Other infections of the choroid and retina. Toxoplasmosis, histoplasmosis, Lyme disease, syphilis, tuberculosis, and ocular toxocariasis. AB - The major clinical infectious syndromes involving the retina and choroid are discussed. Means for successful diagnosis and treatment are presented, as well as the major complications. This work emphasizes the need to identify the infectious nature of these syndromes in order to avoid the all-too-common pitfall of just treating all cases of uveitis with steroids alone. PMID- 1460270 TI - Human immunodeficiency virus and opportunistic ocular infections. AB - Opportunistic ocular infections are a common and important complication of the acquired immunodeficiency syndrome. Cytomegalovirus retinitis is by far the most frequent infection, but other viral, bacterial, and parasitic infections of the posterior segment of the eye may be seen. Infections of the anterior segment are less common but may cause visual loss if not treated. Prompt recognition of these diseases is essential because ocular involvement may be an early sign of systemic dissemination. PMID- 1460271 TI - Infections of the lacrimal system. AB - Deficiency of the tears or obstruction to the free flow of tears predispose to infections of the lacrimal system. The relevant anatomy of the lacrimal system and the pathologic conditions leading to obstruction are outlined. The clinical manifestations of infections of the lacrimal gland, the canaliculus, and the lacrimal sac are described, and the basis for medical and surgical treatment is discussed. PMID- 1460272 TI - Preseptal and orbital cellulitis. AB - The patient with a tender, erythematous, swollen eyelid represents a complex clinical challenge to the physician, who must arrive at a correct diagnosis from numerous differential possibilities. Knowledge of the anatomy of the orbit and surrounding structures and proper clinical and radiologic examination are necessary to accurately diagnose these conditions. Proper selection of antibiotic therapy and timely surgical intervention, directed at both the orbital infection and the underlying condition, are essential to avoid serious morbidity from these infections. This article reviews in detail preseptal cellulitis, Hemophilus influenzae type B infection in children, orbital infection related to paranasal sinusitis, orbital infection from other causes, and mycotic infections of the orbit. PMID- 1460273 TI - Ocular leprosy. AB - Leprosy, also known as Hansen's disease, affects millions of people worldwide and is largely confined to the developing world. Although Hansen's disease is disfiguring, crippling, and even blinding in its later stages, it is not commonly lethal but gradually steals sensory input from the digits and the visual pathways. In this article, the epidemiology and pathogenesis of leprosy are reviewed, with an emphasis on ocular involvement, treatment, and prevention. PMID- 1460274 TI - Onchocerciasis. AB - Onchocerciasis is a parasitic disease with blinding consequences infecting approximately 18 million persons worldwide. In hyperendemic areas, nearly half the population are likely to become blind before they die. Blindness reduces the life expectancy of those affected and has an enormous socioeconomic impact on these communities. Ivermectin, given as a single oral dose of 150 micrograms/kg, can control the manifestations of the disease and can be safely distributed on a mass scale in endemic areas. This drug provides hope for the control of what has been until now an untreatable and devastating disease. PMID- 1460275 TI - T cell recognition of QA-1b antigens on cells lacking a functional Tap-2 transporter. AB - MHC class Ia H chains and beta 2-microglobulin assemble with appropriate peptides to form stable cell surface molecules that serve as targets for Ag-specific CTL. The structural similarities of class Ia and the less polymorphic Q/T/M (class Ib) molecules suggest that class Ib molecules also play a role in antigen presentation, although the origin of the peptides they present remains mostly unclear. The cell line RMA-S has a defect in class I Ag presentation, presumably due to a mutation in a peptide transporter gene. This defect can be overcome by transfection of RMA-S cells with the Tap-2 gene (formerly Ham-2) that encodes an ATP-binding transporter protein. We now show that a substantial portion of alloreactive CTL specific for Qa-1 class Ib molecules recognize Qa-1b on RMA-S cells and thus differ from most class Ia specific CTL. Those anti-Qa-1b CTL that do not recognize untransfected RMA-S do lyse RMA-S transfected with Tap-2. We also examine the effects of Qdm, a gene that maps to the D region and alters recognition of Qa-1. Qdm(k) strains lack an epitope(s) recognized by some (Qdm dependent) anti-Qa-1 CTL whereas Qdm+ strains express this epitope. Thus, Qdm dependent CTL do not recognize Qa-1 on Qdm(k) targets whereas Qdm-independent CTL recognize Qa-1 epitopes in all strains. Although Qdm-independent CTL varied as to whether they recognized RMA-S vs RMA, all nine Qdm-dependent clones only recognized Qa-1b on RMA and not RMA-S. This result is consistent with Qdm encoding a peptide dependent upon the TAP transporter for cell membrane expression. PMID- 1460276 TI - Direct binding of peptides to MHC class I molecules on living cells. Analysis at the single cell level. AB - To directly assess the binding of exogenous peptides to cell surface-associated MHC class I molecules at the single cell level, we examined the possibility of combining the use of biotinylated peptide derivatives with an immunofluorescence detection system based on flow cytometry. Various biotinylated derivatives of the adenovirus 5 early region 1A peptide 234-243, an antigenic peptide recognized by CTL in the context of H-2Db, were first screened in functional assays for their ability to bind efficiently to Db molecules on living cells. Suitable peptide derivatives were then tested for their ability to generate positive fluorescence signals upon addition of phycoerythrin-labeled streptavidin to peptide derivative bearing cells. Strong fluorescent staining of Db-expressing cells was achieved after incubation with a peptide derivative containing a biotin group at the C terminus. Competition experiments using the unmodified parental peptide as well as unrelated peptides known to bind to Kd, Kb, or Db, respectively, established that binding of the biotinylated peptide to living cells was Db-specific. By using Con A blasts derived from different H-2 congenic mouse strains, it could be shown that the biotinylated peptide bound only to Db among > 20 class I alleles tested. Moreover, binding of the biotinylated peptide to cells expressing the Dbm13 and Dbm14 mutant molecules was drastically reduced compared to Db. Binding of the biotinylated peptide to freshly isolated Db+ cells was readily detectable, allowing direct assessment of the relative amount of peptide bound to distinct lymphocyte subpopulations by three-color flow cytometry. While minor differences between peripheral T and B cells could be documented, thymocytes were found to differ widely in their peptide binding activity. In all cases, these differences correlated positively with the differential expression of Db at the cell surface. Finally, kinetic studies at different temperatures strongly suggested that the biotinylated peptide first associated with Db molecules available constitutively at the cell surface and then with newly arrived Db molecules. PMID- 1460277 TI - Role of neuroendocrine hormones in murine T cell development. Growth hormone exerts thymopoietic effects in vivo. AB - Growth hormone (GH) and other neuroendocrine mediators have been implicated previously in T cell development. We therefore examined thymic development in DW/J dwarf mice. DW/J mice lack acidophilic anterior pituitary cells and consequently are totally deficient in the production of GH, as well as other neuroendocrine hormones. DW/J dwarf mice had greatly hypoplastic thymi that continued to decrease in size as the mice aged. Characterization of the different T cell subpopulations within the thymi of dwarf mice indicated a deficiency in CD4+/CD8+ double-positive thymocytes. This deficiency of progenitor cells became more complete as the mice aged culminating in the total disappearance of this subpopulation in some dwarf mice > 3 mo of age. Analysis of the lymph nodes indicated that a population of double-positive (CD4/CD8) T cells appeared in some mice concurrent with the disappearance of double-positive cells in the thymus suggesting that these thymocytes may have migrated to the periphery. However, peripheral T cells from dwarf mice did exhibit Ag-specific responses indicating that these mice have functional T cells. Treatment of the mice with recombinant human GH, which binds both murine growth hormone receptors and murine prolactin receptors, or ovine GH, which binds murine growth hormone receptors but not murine prolactin receptors, resulted in an increase in thymic size and the reappearance of the CD4+/CD8+ double-positive cells within the thymus. Additionally, after GH treatment, the double-positive cells disappeared from the lymph nodes. The thymi of mice treated with GH failed to attain normal size but did develop a normal distribution of T cell progenitors. Thus, GH exerts significant thymopoietic effects in vivo. Neuroendocrine hormones may be important for normal T cell differentiation to occur within the murine thymus. PMID- 1460279 TI - Increased avidity of mutant IgM antibodies caused by the absence of COOH-terminal glycosylation of the mu H chain. AB - We have previously described the isolation of two hybridoma variants secreting higher avidity IgM (D5 and 7F5), starting from the E11 hybridoma cell line, which produces an antibody specific for the A Ag of the ABO blood group system. In order to explain at the molecular level this increased reactivity, cDNA encoding the H and L chains of the E11, D5, and 7F5 mAb were cloned and sequenced. Comparison of the nucleotide sequences showed a single point mutation in each of the two mAb produced by the hybridoma variants. The mutations were both located in the H chain C region and caused a Ser to Phe substitution at position 565 in the D5 mAb and a Asn to Tyr substitution at position 563 in the 7F5 mAb. Both substitutions modified the consensus glycosylation sequence (Asn-X-Ser/Thr) located in the tail piece of the secretory mu-chain. The absence of glycosylation at this site was confirmed by CNBr cleavage of the [14C]mannose-labeled mAb. The two single point mutations were solely responsible for the increased avidity of the antibodies, as confirmed by site-directed mutagenesis of the E11 mu-chain and serologic analysis of the mutated E11 antibodies. We conclude that the absence of glycosylation at Asn 563 is responsible for the increased avidity of the mutant, possibly by altering the quaternary structure of the IgM polymer. To our knowledge, this is the first report that point mutations in the H chain C region can influence the reactivity of IgM mAb. PMID- 1460278 TI - Systemic suppression of delayed-type hypersensitivity by supernatants from UV irradiated keratinocytes. An essential role for keratinocyte-derived IL-10. AB - Exposing murine keratinocyte cultures to UV radiation causes the release of a suppressive cytokine that mimics the immunosuppressive effects of total-body UV exposure. Injecting supernatants from UV-irradiated keratinocyte cultures into mice inhibits their ability to generate a delayed-type hypersensitivity reaction against allogeneic histocompatibility Ag, and spleen cells from mice injected with supernatant do not respond to alloantigen in the in vitro MLR. A unique feature of the immunosuppression induced by either total-body UV-exposure or injecting the suppressive cytokine from UV-irradiated keratinocytes is the selectivity of suppression. Although cellular immune reactions such as delayed type hypersensitivity are suppressed antibody production is unaffected. Because the selective nature to the UV-induced immunosuppression is similar to the biologic activity of IL-10, we examined the hypothesis that UV exposure of keratinocytes causes the release of IL-10. Keratinocyte monolayers were exposed to UV radiation and at specific times after exposure mRNA was isolated or the culture supernatant from the cells was collected. IL-10 mRNA expression was enhanced in UV-irradiated keratinocytes. The secretion of IL-10 by the irradiated keratinocytes was determined by Western blot analysis. A band reactive with anti IL-10 mAb was found in supernatants from the UV-irradiated but not the mock irradiated cells. IL-10 biologic activity was determined by the ability of the supernatants from the UV-irradiated keratinocytes to suppress IFN-gamma production by Ag-activated Th 1 cell clones. Anti-IL-10 mAb neutralized the ability of supernatants from UV-irradiated keratinocytes to suppress the induction of delayed-type hypersensitivity in vivo. Furthermore, injecting UV irradiated mice with antibodies against IL-10 partially inhibited in vivo immunosuppression. These data indicate that activated keratinocytes are capable of secreting IL-10 and suggest that the release of IL-10 by UV-irradiated keratinocytes plays an essential role in the induction of systemic immunosuppression after total-body UV exposure. PMID- 1460280 TI - Role of protein kinase C activity in tumor necrosis factor-alpha gene expression. Involvement at the transcriptional level. AB - Primary rat astrocytes express TNF-alpha protein in response to various stimuli including a combined treatment with IFN-gamma and LPS, or IFN-gamma and IL-1 beta. This study was undertaken to further elucidate the mechanisms underlying TNF-alpha gene expression in the astrocyte, and to determine the intracellular signaling pathways involved in IFN-gamma/LPS and/or IFN-gamma/IL-1 beta induction of the TNF-alpha gene. We demonstrate that TNF-alpha mRNA is rapidly induced, and mRNA levels peak after 2 h of stimulation. De novo protein synthesis is not required for TNF-alpha expression because the inclusion of cycloheximide does not prevent expression of the gene and acts to superinduce TNF-alpha mRNA levels. IFN gamma/LPS induces transcriptional activation of the TNF-alpha gene as assessed by nuclear run-on experiments. Cycloheximide acts to increase both transcription of the TNF-alpha gene and stability of TNF-alpha mRNA thereby resulting in increased TNF-alpha steady state mRNA levels. Two protein kinase C (PKC) inhibitors, H7 and staurosporine, abrogate IFN-gamma/LPS- and IFN-gamma/IL-1 beta-induced TNF-alpha expression in a dose-dependent manner. PKC activity is required for transcription of the TNF-alpha gene, and does not appear to be involved in TNF-alpha mRNA stabilization. Taken together, these data demonstrate that TNF-alpha gene expression in primary rat astrocytes is induced in a PKC-dependent manner. PMID- 1460281 TI - Antibody engineering by codon-based mutagenesis in a filamentous phage vector system. AB - A novel codon-based mutagenesis procedure is described that allows rapid and efficient modification of antibody amino acid sequences expressed as F(ab) fragments in M13. The procedure succeeded in generating a library of mutations in the complementarity-determining regions of chimeric L6, an antibody against a tumor-associated Ag. A set of anti-Id antibodies (anti-Id 1, 3, and 7) that bind near the L6 Ag-binding site served as model Ag. The goal was to select mutant antibody sequences that altered the L6 reactivity with the anti-Id in subtle ways, i.e., to eliminate the binding to one anti-Id while preserving other reactivities or to identify mutants with increased binding. A high frequency of variant M13 phage clones exhibiting altered specificity for the anti-Id were identified. Codon-based mutagenesis in conjunction with the M13 antibody expression and screening system should provide an efficient and general approach for redirecting the specificity and potentially improving the affinity of antibodies in vitro. PMID- 1460282 TI - Application of a filamentous phage pVIII fusion protein system suitable for efficient production, screening, and mutagenesis of F(ab) antibody fragments. AB - We describe the application of a novel filamentous phage vector system suitable for efficient screening and production of F(ab) antibody fragments. The vector system can concurrently produce free F(ab) fragments and F(ab) displayed on the surface of M13 bacteriophage via a VHCH1-pVIII fusion protein. When expressed in a supO (nonsuppressor) strain of Escherichia coli free F(ab) can be produced. Antibody F(ab) fragments are secreted into culture medium at concentrations up to 0.3 mg/liter and conveniently subjected to detailed analysis with little or no purification. Higher concentrations of F(ab) (approximately 10 mg/liter) were found to accumulate in the periplasmic space. In this report the vector system is shown to produce correctly folded and assembled F(ab) fragments of chimeric L6, a mAb against a tumor-associated Ag expressed by many human carcinomas. PMID- 1460283 TI - L chain isotype regulation in horse. I. Characterization of Ig lambda genes. AB - Analysis of 10 cDNA encoding lambda L chains of horse Ig indicated that this species may employ a relatively small number of variable region (V lambda) genes in the splenic B cell population. The V lambda sequences of all of the cDNA analyzed were closely related (> 88% identity at the nucleotide level) and were characterized by a deletion of the amino acid residue at position 3 compared with V lambda sequences so far described in other species. The 10 V lambda sequences could be grouped into three groups, V lambda 1 to V lambda 3, on the basis of a number of linked substitutions. Sequences within the groups showed the greatest divergence in the third cdr regions and at the V-J junctions. The junctional variation included amino acid substitutions on both sides of the V-J junction as well as the insertion or deletion of two to four amino acid residues. Four C lambda genes were identified in genomic blots of horse DNA, and three of these were found expressed in splenic cDNA. The fourth C lambda gene may represent a pseudogene, inasmuch as the associated J region possessed a defective heptamer joining sequence. Six of the nine possible V lambda-C lambda combinations were found in the cDNA analyzed, suggesting that genes belonging to groups V lambda 1 through V lambda 3 may rearrange to any one of three J lambda-C lambda genes. One V lambda germline gene was characterized and found to represent a distinct V lambda group (V lambda 4), not represented in the cDNA sequences analyzed. The number of germline V lambda genes was estimated to be 20 to 30, based on analysis of restriction fragments hybridizing with V lambda probes. On the basis of these data, we propose that the V lambda repertoire in horse may consist of relatively limited number of genes, of which only a few may be used at high frequency in the splenic B cell population. The results indicate that predominance of lambda chains in horse Ig may not simply be due to the presence of a large germline V lambda gene repertoire. PMID- 1460284 TI - Nucleotide sequence of messenger RNA encoding VHDJH and VKJK of a highly conserved idiotype-defined primary response anti-hapten antibody. AB - The primary humoral immune response of mice to the hapten phthalate (Xmp) is focused upon two adjacent immunodominant negatively charged carboxyl groups on a benzene ring that are in positions meta and para to the azolinkage (i.e., Xmp) to the protein carrier keyhole limpet hemocyanin. A significant fraction of the anti Xmp antibodies raised in several different inbred mouse strains (BALB/c, DBA/2, A/HeHa; C3H, and SM/J), and many wild mouse populations express a cross-reactive Id, CRIXmp-1. This CRIXmp-1 is conspicuously absent in C57BL/6 mice. In order to obtain a better understanding of the events and parameters that influence the selection and regulation of the primary response B cell repertoire, and to explore the structural basis of Ag binding, we have determined the nucleotide sequence of the entire V region gene complexes, which encode the H and L chains of these highly conserved and dominant CRIXmp-1+ antibodies. Our data establish that the H chain gene complex consists of a single VH germ-line gene that is identical to VH Oxazolone-1, encoding the H chain of another highly conserved and dominant cross-reactive Id family associated with the primary response to Oxazolone. In CRIXmp-1+ Xmp-specific hybridomas this gene is joined to a limited set of D region sequences that express a conserved amino acid motif-GLR. At least three of the five D regions examined are coded for by DFL16.2. This VHD complex can be utilized with one of three different JH region genes (JH1, JH2, and JH4) without any significant effect upon antibody fine specificity or Id. In spite of this lack of JH fidelity all of the CRIXmp-1+ hybridomas have precisely maintained the same length in the H chain CDR3 and FRW4 by altering either the length of the D segment or the length of JH. Nucleotide sequence analysis of the VL gene complex of CRIXmp-1+ anti-Xmp antibodies indicates that the L chain V region is also encoded by a single germ-line gene. The amino acid sequence predicted from the nucleotide sequence of the VKJK from Xmp-specific CRIXmp-1+ hybridomas is identical to the sequence of the anti-arsonate antibody 1210.7, which is the prototype of another Id family (CRI) that is conserved and dominant in BALB/c mice. PMID- 1460285 TI - Genes encoding Xenopus laevis Ig L chains. Implications for the evolution of kappa and lambda chains. AB - Xenopus laevis Ig contain two distinct types of L chains, designated rho or L1 and sigma or L2. We have analyzed Xenopus genomic DNA by Southern blotting with cDNA probes specific for L1 V and C regions. Many fragments hybridized to the V probe, but only one or two fragments hybridized to the C probe. Corresponding C, J, and V gene segments were identified on clones isolated from a genomic library prepared from the same DNA. One clone contains a C gene segment separated from a J gene segment by an intron of 3.4 kb. The J and C gene segments are nearly identical in sequence to cDNA clones analyzed previously. The C segment is somewhat more similar and the J segment considerably more similar in sequence to the corresponding segments of mammalian kappa chains than to those of mammalian lambda chains. Upstream of the J segment is a typical recombination signal sequence with a spacer of 23 bp, as in J kappa. A second clone from the library contains four V gene segments, separated by 2.1 to 3.6 kb. Two of these, V1 and V3, have the expected structural and regulatory features of V genes, and are very similar in sequence to each other and to mammalian V kappa. A third gene segment, V2, resembles V1 and V3 in its coding region and nearby 5'-flanking region, but diverges in sequence 5' to position -95 with loss of the octamer promoter element. The fourth V-like segment is similar to the others at the 3'-end, but upstream of codon 64 bears no resemblance in sequence to any Ig V region. All four V segments have typical recombination signal sequences with 12-bp spacers at their 3'-ends, as in V kappa. Taken together, the data suggest that Xenopus L1 L chain genes are members of the kappa gene family. PMID- 1460286 TI - Effect of Haemophilus influenzae polysaccharide outer membrane protein complex conjugate vaccine on macrophages. AB - Haemophilus influenzae type b polysaccharide-conjugate vaccines elicit protective antibody responses in young infants. One of these conjugates, polysaccharide linked to outer membrane protein complex (PRP-OMPC), is produced by linking the capsular polysaccharide to an outer membrane protein complex derived from group B Neisseria meningitidis. The outer membrane protein complex contains T cell carrier epitopes that elicit T cell-dependent antibody responses. OMPC also has been shown to increase the antibody response to other proteins administered concurrently that are not covalently linked (i.e., acts as an adjuvant). In this study PRP-OMPC immunized mice demonstrated significant increases in spleen size as well as in splenocyte number as compared to saline controls (p < 0.01, p < 0.001, respectively). No such increase was noted after immunization with another H. influenzae type b-conjugate vaccine, oligosaccharide linked to a variant of diphtheria toxin. By analytic flow cytometry, the mice immunized with PRP-OMPC demonstrated an increase in large splenocytes expressing the Ag Mac-1 (CD11b, CR3). Furthermore, the spleens on histologic examination were characterized by an increase in the red pulp area consisting predominantly of cells of macrophage morphology. By immunohistochemical staining, the cells were identified as macrophages due to expression of Mac-1 and p150,95 (CD11C) Ag. After PRP-OMPC immunization, severe combined immunodeficient mice also demonstrated significant splenomegaly with an increase in macrophages identified by expression of Mac-1 and MHC class II Ag. Thus PRP-OMPC vaccine resulted in T cell-independent splenomegaly with an increase number of macrophages. We propose that this unique property may confer increased immunogenicity to PRP-OMPC through macrophage activation and cytokine release. Furthermore, the effect on macrophages may explain the "adjuvant" capacity of OMPC. PMID- 1460287 TI - Transfection of mouse cytotoxic T lymphocyte with an antisense granzyme A vector reduces lytic activity. AB - Murine CTL have seven serine proteases, known as granzymes, in their lytic granules. Despite considerable effort, convincing evidence that these enzymes play an obligatory role in the lytic process has not been presented. To investigate the function of one of these proteases, granzyme A (GA), we utilized an antisense expression vector to lower the level of the enzyme in the cells. An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1. Transfectants were selected based on resistance to hygromycin B, and a number of stable lines were developed. One of the antisense lines had greatly reduced levels of GA mRNA, when compared to the parental cells or to control lines transfected with the vector lacking the antisense DNA. The message levels for two other CTL granule proteins, granzyme B and perforin, were unaffected by the antisense vector. The amount of GA, as measured by enzymatic activity, was 3- to 10-fold lower in the transfectant. Most significantly, this line also consistently showed 50 to 70% lower ability to lyse nucleated target cells and to degrade their DNA. Furthermore, it exhibited 90 to 95% lower lytic activity to anti-CD3-coated SRBC. Conjugate formation with target cells, however, was normal. These data provide strong evidence that GA plays an important role in the cytolytic cycle, and that the quantity of enzyme is a limiting factor in these cytolytic cells. PMID- 1460289 TI - IL-10 stimulates monocyte Fc gamma R surface expression and cytotoxic activity. Distinct regulation of antibody-dependent cellular cytotoxicity by IFN-gamma, IL 4, and IL-10. AB - T cell-derived cytokines IFN-gamma and IL-4 have different regulatory effects on two functionally important molecules on human monocytes: MHC class II Ag and the Fc receptor for monomeric IgG, Fc gamma RI (CD64). MHC class II Ag, and Fc gamma RI are both upregulated in the presence of IFN-gamma. IL-4 induces MHC class II Ag expression but reduces Fc gamma RI expression. Recently, we showed that the cytokine IL-10 also affects MHC class II Ag expression. Here, we demonstrate that in contrast to the down-regulation of MHC class II Ag expression, IL-10 stimulates Fc gamma RI expression on human monocytes comparable to the levels of Fc gamma RI expression induced by IFN-gamma. The IL-10-induced Fc gamma RI expression is specific because anti-IL-10 antibodies completely reverse the IL-10 induced surface expression of Fc gamma RI and correlate with an enhanced capacity to lyse anti-D-coated human rhesus-positive erythrocytes. IL-10 fails to induce the expression of Fc gamma RII (CD32) and Fc gamma RIII (CD16). Furthermore, we demonstrate that IL-10 is able to prevent down-regulation in surface membrane expression of all three Fc gamma R that can be found when monocytes are cultured in the presence of IL-4. In contrast to IFN-gamma, IL-10 does not restore the reduced antibody-dependent cellular cytotoxicity (ADCC) activity of IL-4-cultured monocytes. Together, these results show that, similar to IFN-gamma, IL-10 is capable of enhancing Fc gamma R expression and ADCC activity, and that IFN-gamma, IL-4, and IL-10 have different regulatory effects on both monocyte Ag-presenting capacity and ADCC activity. PMID- 1460288 TI - Eosinophil transendothelial migration induced by cytokines. I. Role of endothelial and eosinophil adhesion molecules in IL-1 beta-induced transendothelial migration. AB - IL-1 beta promotes adhesiveness in human umbilical vein endothelial cells (HuVEC) for eosinophils through expression of adhesion molecules including intercellular adhesion molecules-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1). Using an in vitro endothelial monolayer system, we examined whether IL 1 beta or TNF-alpha can promote eosinophil transendothelial migration. We also evaluated the contributions of ICAM-1, E-selectin, VCAM-1, leukocyte adhesion complex (CD11/18), and very late Ag-4 (CD11b/18) (VLA-4) in this process using blocking mAb, and determined the changes in expression of CD11b and L-selectin on eosinophils that had undergone transmigration. IL-1 beta and TNF-alpha treatment of HuVEC (4 h, 5 ng/ml) induced significant transendothelial migration of eosinophils (a 4.1 +/- 0.4-fold (IL-1 beta) and 2.0 +/- 0.9-fold (TNF-alpha) increase from the spontaneous value of 3.2 +/- 0.3%). Increased CD11b expression and shedding of L-selectin were observed on eosinophils following IL-1 beta induced eosinophil transendothelial migration. Studies with mAb revealed that blockade of either ICAM-1 or CD11/18 inhibited transmigration, while antibodies against VCAM-1 and VLA-4 had no inhibitory effect. Among antibodies which block beta 2 integrins, anti-CD18 mAb had the best inhibitory effect (88% inhibition). The combined inhibitory effect of anti-CD11a mAb and anti-CD11b mAb was roughly equal to that of anti-CD18, although anti-CD11a (31% inhibition) and anti-CD11b (52% inhibition) were less effective individually. Anti-ICAM-1 by itself inhibited IL-1 beta-induced eosinophil transendothelial migration (24% inhibition) whereas neither anti-E-selectin nor anti-VCAM-1 were effective inhibitors. Interestingly, the combination of anti-E-selectin and anti-VCAM-1 with anti-ICAM-1 inhibited IL-1 beta-induced eosinophil transendothelial migration significantly better (53% inhibition) than anti-ICAM-1 alone. These results suggest that although the initial attachment of eosinophils to IL-1 beta activated endothelial cells involves VCAM-1, E-selectin, and ICAM-1, the subsequent transendothelial migration process relies heavily on ICAM-1 and CD11/18. Finally, the changes that eosinophils have been observed to undergo during infiltration in vivo, namely increased expression of CD11/18 and shedding of L-selectin, appear to take place as a direct result of the interaction between eosinophils and endothelial cells. PMID- 1460290 TI - Probing the human antibody repertoire to exogenous antigens. Characterization of the H and L chain V region gene segments from anti-hepatitis B virus antibodies. AB - Structural studies of human antibody V regions have been largely limited to those involving the fetal repertoire, autoantibodies, and malignant cell rearrangements, leaving the "normal" repertoire relatively unexplored. In this study we describe the nucleotide sequences of the H and L chain V regions of four antibodies specific for the surface Ag of the hepatitis B virus. Monoclonal cell lines were derived from healthy individuals who received standard immunizations with the serum-derived or recombinant hepatitis B virus vaccines by fusion of PBL to a heterohybridoma cell line, SPAZ-4. We utilized the polymerase chain reaction to amplify the H and L chain V regions for cloning and sequencing. The four antibodies express the following V region combinations: VHIII/V lambda V, VHIII/V kappa II, VHIV/V kappa I, VHV/V lambda III. When compared to germline genes with the closest sequence homology, all of the V regions appear to have undergone somatic mutation, ranging from 3.4 to 11.3% for the H chain, and 5.1 to 9.2% for the L chain. Analysis of the mutations shows them to be typical for an Ag-driven immune response. PMID- 1460291 TI - Cytotoxic T lymphocytes do not appear to select for mutations in an immunodominant epitope of simian immunodeficiency virus gag. AB - Studies to date assessing HIV escape from CTL in vivo have yielded conflicting results. Previous studies have demonstrated that simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys expressing the MHC class I allele Mamu A*01 reproducibly develop a gag-specific CTL response limited to a 9-amino acid epitope of the SIVmac gag protein (residues 182-190 within peptide 11C). To determine whether CTL have a role in selecting for AIDS virus mutants, we examined mutations in SIVmac proviral DNA encoding this gag CTL epitope in PBL of infected rhesus monkeys. Three Mamu-A*01+ rhesus monkeys were infected with SIVmac and assessed for gag- and peptide 11C-specific CTL responses. This specific CTL response was maintained in two monkeys, but lost in the third animal 2 yr after infection. The generation of proviral gag mutations was then determined by sequencing 500-bp proviral fragments amplified from fresh PBL obtained from the monkeys more than 2.5 yr after infection. Although numerous point mutations were characterized in 131 polymerase chain reaction-generated clones of SIVmac gag, only four mutations within the gag CTL epitope-coding region of the genome were identified. Comparison of synonymous and nonsynonymous nucleotide substitutions in the regions encoding peptide 11C (p11C) and the flanking gag protein indicated a lack of selective pressure for viral mutations in the CTL epitope coding region. Interestingly, a predominant gag mutant encoding a single amino acid change in p11C was found in a monkey which lost its CTL activity. However, even in this setting there was no evidence for selection of mutations in the CTL epitope coding region when compared with the flanking region. Furthermore, synthetic peptides corresponding to all naturally occurring variants in the gag epitope-coding region were recognized by cloned and bulk cultured effector cells of the infected monkeys with persistent CTL. These results indicate that SIVmac gag- and p11C-specific CTL do not select for mutations in the immunodominant epitope-coding region and that the naturally occurring mutants do not appear to escape CTL recognition. PMID- 1460292 TI - IFN-gamma receptor-Ig fusion proteins. Half-life, immunogenicity, and in vivo activity. AB - Two mouse IFN-gamma receptor (MoIFN gamma R)-Ig fusion proteins, which were constructed for the purpose of creating new efficient mouse IFN-gamma (MoIFN gamma) inhibitor molecules, were studied in vivo to determine their plasma half life and immunogenicity, and to show their biologic activity. The hybrid proteins show 40-h blood persistency. They do not provoke an antibody response when injected into mice, and they are biologically active in vivo, as demonstrated by the prevention of streptozotocin-induced diabetes. The two fusion proteins are efficient MoIFN-gamma antagonists and can be used in mouse models of human diseases to investigate the role of MoIFN gamma in these pathologic states. PMID- 1460293 TI - Infection of human natural killer (NK) cells with replication-defective human T cell leukemia virus type I provirus. Increased proliferative capacity and prolonged survival of functionally competent NK cells. AB - Human T-cell leukemia virus type I (HTLV-I) can infect a variety of human cell types, but only T lymphocytes are efficiently immortalized after HTLV-I infection. This study reports an attempt to infect and to immortalize NK cells with HTLV-I. Co-cultivation of freshly isolated NK cells with a HTLV-I-producing T cell line did not result in NK cell infection. However, NK cells activated with an anti-CD16 mAb and co-cultivated with a HTLV-I-producing T cell line were reproducibly infected by HTLV-I. HTLV-I infection was documented in NK cell lines and clones by the detection of defective integrated provirus by both Southern blot and polymerase chain reaction analysis. Although HTLV-I-infected NK cells produced viral proteins, they did not produce infectious viral particles. HTLV-I infected NK cells were phenotypically indistinguishable from their uninfected counterparts (CD16+, CD2+, CD56+, CD3-). They also retained the ability to mediate both natural and antibody-dependent cell cytotoxicity. The IL-2-dependent proliferation of HTLV-I-infected NK cells was significantly greater than that of uninfected NK cells. The doubling time of this infected population was reduced from 9 days to 3 days, and the overall survival of the culture in the absence of restimulation was extended from 5 wk to 18 wk. Unlike T lymphocytes, HTLV-I infected NK cells were not immortal, implying a fundamental difference between these two lymphocyte populations. PMID- 1460294 TI - Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. AB - We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, C15, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and anti-OVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CD5, and TCR-alpha/beta. Three of the seven clones used TCR-V beta 4. However, the V beta expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-gamma. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen. PMID- 1460296 TI - Medical education--expectations and reality. PMID- 1460295 TI - Medical education in India: present status and future perspective. PMID- 1460297 TI - Sophistication in medical technology. PMID- 1460298 TI - Graduate medical education: reappraisal. PMID- 1460299 TI - Teaching of pathology and microbiology in Medical College, Calcutta. PMID- 1460300 TI - Anatomy: the foundation in medical technology and its role in medical education. PMID- 1460301 TI - Teaching and training in geriatric medicine. PMID- 1460302 TI - Medical admissions: a confusing disease. AB - It is strictly for admission to undergraduate medical courses. (i) 50% of seats should be reserved for local candidate on merit of HSC, with academic year starting after the HSC results. (ii) 20% of seats should be reserved for candidates coming from rural areas, on the basis of merit at HSC, with academic year starting after HSC results. (iii) 30% of seats to be filled by an all-India competitive examination. The academic year to start 6 months after the HSC results. A ceiling of minimum number of marks and a minimum number of attempts for eligibility to the all-India PMT would make the conduct of such an examination more practical. PMID- 1460303 TI - Medical education de-valued. 1975. PMID- 1460304 TI - Medical education in India since independence. 1981. PMID- 1460305 TI - Medical education. 1981. PMID- 1460306 TI - Scientific misconduct in medical research. PMID- 1460307 TI - Postgraduate training in the United Kingdom: details of double sponsorship training programme. PMID- 1460308 TI - Tamilising medical education--a retrograde step. PMID- 1460310 TI - The medical role in environmental health. PMID- 1460309 TI - Family physician to regain his glory--certain random thoughts. PMID- 1460311 TI - Treatment of acute respiratory infection in children by practitioners in India. PMID- 1460312 TI - Primary malignant lymphoma of the gastro-intestinal tract: a clinicopathological study of 24 cases. AB - Twenty-four cases of primary lymphoma of the gastro-intestinal tract were diagnosed during the period 1970 to 1991. There was a preponderance of males and the male to female ratio being 1.4:1. Age ranged from 9-70 years, mean 32.2 years. Small intestine was involved in 50% cases, large bowel in 9 cases (37.5%) and stomach in 3 cases (12.5%). There were 5 cases (20.8%) of Hodgkin's disease and 19 cases (79.2%) were of non-Hodgkin's lymphoma. All cases of gastric lymphoma complained of epigastric pain, weight loss and vomiting. In lymphoma of small intestine, 8 patients complained of pain associated with vomiting and 6 patients complained of distension of abdomen. In large bowel lymphoma, pain in right iliac fossa was complained by 4 patients and bleeding per rectum by 3 patients. Out of all the 24 cases, changes in bowel habit were noted in 15 patients and occult blood was positive in 13 cases. Palpable abdominal mass was noted in 14 patients. Histomorphologically, all the 3 cases in the stomach were of lymphocytic lymphoma diffuse type. Out of 19 non-Hodgkin's lymphoma, 15 were of lymphocytic lymphoma and 4 were of histiocytic lymphoma. PMID- 1460313 TI - Iatrogenic dry eye: late effect of topical steroid formulations. AB - A total of 69 eyes of 35 patients receiving local corticosteroid therapy over a period of 3 months to 2 years for different eye ailments were studied. It was observed that there was a significant reduction (p < 0.05) of Schirmer's test I, as well as tear film break up time values with an increase in the duration of treatment. Of the various preservatives used with the various brands of steroids it was observed that benzalkonium chloride is most commonly associated with dry eye syndrome. The complications of prolonged topical steroid therapy included steroid induced glaucoma (4 eyes), lenticular opacities (4 eyes), epitheliopathy (2 eyes) and flare up of silent viral keratitis (one eye). PMID- 1460314 TI - Comparative study of midtrimester termination of pregnancy using hypertonic saline, ethacridine lactate, prostaglandin analogue and iodine-saline. AB - The study consisted of terminations of 200 cases of second trimester pregnancies ranging from 14 weeks to 20 weeks. Out of these 200 cases, in 50 cases intra amniotic instillation of 20% hypertonic saline (200 ml) was done after withdrawing 35-200 ml of amniotic fluid. Ethacridine lactate was instilled in 50 cases extra-amniotically. Prostaglandin F2 alpha was injected intramuscularly at regular intervals in 50 cases. Fifty cases of pregnancies were terminated with extra-amniotic instillation of 5% povidone-iodine solution mixed with normal saline. Comparison was made among all the methods regarding instillation-abortion interval, completeness of abortion, failure of the procedure and postoperative complications. Solution of 5% povidone-iodine in normal saline was found to be comparable in all aspects to other methods and above all a much cheaper alternative for poor patients. Success rate was highest with iodine-saline solution (100%) followed by ethacridine lactate (98%), hypertonic saline (96%) and lowest with prostaglandin F2 alpha (90%). PMID- 1460315 TI - The blood group and haemoglobin types of the Santals. AB - A total of 488 blood samples from tribal as well as non-tribal donors of Bihar and West Bengal were analysed for presence of abnormal haemoglobin variants. Out of 488 samples ABO and Rh blood groups were studied in 468 samples. Predominance of group B was noted in both the tribal and non-tribal groups and absence of Rh(d) was noted in non-tribal population with the exception of the tribals where 4.42% Rh(d) gene was found. Incidence of haemoglobin E gene was very low in most cases but relatively higher in non-tribal populations, while the range of raised haemoglobin A2 varied from 5.84% to 8.80%. PMID- 1460316 TI - The natural history of smoking. AB - This study is a small collection of the natural history of smoking of 865 persons - all smokers and majority (97.11%) of them were males, more than 80% were between 21-50 years, most (90%) were Hindus and 75% were service holders. It revealed that most of the subjects started smoking between 10 and 25 years of age, frequently being requested by their friends but felt nothing mentionable at their first experience. Most of them (64%) were smoking for more than 10 years, 48.56% were smoking more than 10 cigarettes in a day, filter-tipped more often (by 64% subjects) and without any history of break by 56% subjects. Majority (80%) used to inhale the smoke and 40% had no specific time of choice. Most of the subjects (80%) like to smoke in deep thoughts, 66% during excitement, 60% when depressed, 82% when relaxed and 62.5% when alone. But most of them (64%) did not smoke when busy. Majority (70.87%) felt relaxed when smoking. Most of the people (45%) stood reasonable having no cigarette in their stock. Majority (84%) used to smoke even when not offered. Tobacco was consumed largely as smoke by 75% subjects; 78% subjects smoked only cigarettes and about half of the smokers smoked even when they did not enjoy it. PMID- 1460317 TI - Angiomyolipoma of kidney. AB - Angiomyolipoma is an uncommon benign tumour accounting for less than 1% of all surgically excised tumours of the kidney. It may present as an isolated lesion or in association with tuberous sclerosis. An impalpable tumour is often detected incidentally during investigation of a case for some urinary tract pathology. CT scan has proved to be a useful investigation for pre-operative diagnosis; it may however, be of no value if the fat content of the tumour is low. Here a case of angiomyolipoma of left kidney is reported where pre-operative diagnosis was suggested by CT scan and histopathology confirmed it. PMID- 1460318 TI - Rare variant of acute promyelocytic leukaemia. AB - Acute promyelocytic leukaemia (APL) is a peculiar sub-type of acute myeloblastic leukaemia characterised by presence of atypical promyelocytes in bone marrow and peripheral blood and common occurrence of haemorrhagic episodes associated with disseminated intravascular coagulation. Two morphological forms of APL are recognised--typical hypergranular and microgranular or M3 variant. This microgranular form of APL is rare but has got some peculiar features and often can be diagnosed by peripheral blood smear examination alone without bone marrow examination. Three cases of microgranular form of APL observed during a period of 6 months are reported here. PMID- 1460319 TI - Giant sized oligodendroglioma of posterior fossa. PMID- 1460320 TI - Human laser assisted angioplasty: clinical results of 42 case trial in peripheral vessels. PMID- 1460321 TI - Treatment of pyogenic meningitis in children. PMID- 1460322 TI - Serum erythropoietin titers in hematological malignancies and related diseases. AB - Serum erythropoietin (Epo) titers in patients with various hematological malignancies and related diseases were determined by radioimmunoassay. Serum Epo titer was inversely correlated with hemoglobin concentration in iron deficiency anemia, aplastic anemia, myelodysplastic syndromes (MDS), acute leukemia, malignant lymphoma, multiple myeloma and myelofibrosis, but there was no correlation between serum Epo titer and hemoglobin concentration in chronic myelogenous leukemia or polycythemias. Serum Epo titers in aplastic anemia were much higher than those in iron deficiency anemia. Serum Epo titers in MDS, malignant lymphoma and multiple myeloma differed considerably among patients. Serum Epo titers in untreated polycythemia vera were significantly lower than in treated polycythemia vera or secondary polycythemia. PMID- 1460323 TI - Peripheral blood hematopoietic progenitor cells in beta-thalassemia major. AB - Colony assays in methylcellulose (semisolid medium) of erythroid precursors and granulocyte-macrophage precursors from the peripheral blood of 34 patients with beta-thalassemia major and 31 age-matched normal controls were studied. In patients homozygous for beta-thalassemia, a significant increase of circulating erythroid progenitor cells to 3-5 times of normal controls was observed. Furthermore, the number of circulating colony forming units-granulocyte macrophage (CFU-GM) and colony forming units-mixed (CFU-Mixed) also increased significantly. In these subjects, there was a linear relationship between the number of burst forming units-erythroid (BFU-E) and CFU-GM. The serum level of erythropoietin (EPO) was also significantly higher than that of normal controls (p < 0.05). The increased hematopoiesis, indicated by an increased number of circulating hematopoietic progenitor cells and an elevated serum level of EPO, suggests that the physiologic regulation of erythropoiesis still operated in patients with beta-thalassemia major. PMID- 1460324 TI - An in vitro thymidine incorporation assay for human cancers: technical details revisited. AB - Among the choices of laboratory methods for in vitro testing of human tumor chemosensitivity, a thymidine incorporation assay (TIA) has been described. Advantages of a TIA over a colony-forming assay include greater probability of tumor growth, requirement for fewer tumor cells, less dependence on an absolute single-cell suspension, shorter time to completion, and the ability to measure up to three logs cell-kill. Specific technical details which are reported in the literature for performing a TIA are incomplete and/or conflicting between one laboratory and another. This paper reports details of methods designed to remove unbound 3[H]-thymidine from the agarose, standardize background counts, and determine optimal cell-plating densities, labeling time, optimal concentration of 3[H]-thymidine, and the best day after seeding cultures to add the 3[H] thymidine. Care has been taken to compare the end point of drug sensitivity determinations following these methodologic changes, both among serial TIAs as well as with colony-forming assays. PMID- 1460325 TI - Cloning of human tumor cell lines in porous glass capillary tubes: a further development of the human tumor stem cell assay. AB - The conventional human tumor stem cell assay for cloning tumor cells for drug sensitivity testing is limited by its inability to test drug combinations. In an attempt to overcome this limitation, we cloned tumor cell lines within porous glass capillary tubes. In contrast to plastic porous tubes, the porous glass membranes were transparent, and colony formation could be judged on an inverted microscope. Human as well as animal cell lines showed sufficient colony growth. Colonies formed within these porous tubes were homogeneously distributed, and their morphology was similar to those formed in the common stem cell assay. Cloning efficiency and colony size depended on the mean pore diameter of the glass membrane, with best colony growth within tubes with a pore diameter ranging from 8.5 nm to 14 nm. A linear relationship between number of cells seeded and number of grown colonies could be demonstrated for the cell lines MDA-231 and Colo 201. Colony growth achieved within porous glass capillary tubes is comparable to that achieved in Petri dishes and in nonporous tubes. We conclude that the porous capillary cloning system meets the basic suppositions for a quantitative cloning assay. Moreover, the porosity of the glass membrane offers the possibility of variable perfusion of medium and drugs. Further investigations will focus on various perfusion modalities and chemosensitivity testing. PMID- 1460326 TI - Influence of feeding regimen and postnatal developmental stages on antibacterial activity of pancreatic juice. AB - Antibacterial activity of pancreatic juice in the pig (n = 8) was investigated during early postnatal development and in cattle (n = 6) receiving a different feeding regimen. For pancreatic juice collection, a catheter was surgically implanted in the pancreatic duct. Reintroduction of pancreatic juice was achieved through a T-shaped cannula in the duodenum. Pancreatic juice was collected for 30 min in all cases. In piglets, collections were carried out at 2, 5-6, and 7-10 wk of age, and in cattle, after a standard meal, 48 h starvation, and following 24 h intraduodenal glucose infusion. Antibacterial activity was tested on Micrococcus Pyogenes strain ATTC 6538P by disc agar diffusion technique using nonactivated pancreatic juice, before and after heat treatment for 15 min at 65 and 100 degrees C, respectively. Piglets showed a significant rise in antibacterial activity of pancreatic juice after weaning. In cattle, 48 h of starvation resulted in a marked suppression of antibacterial activity. This activity was found to be normal after a standard meal and comparable to that after 24-h intraduodenal glucose infusion. Heating of pancreatic juice to 65 degrees C caused a 35% increase in the antibacterial potency, whereas heating to 100 degrees C completely abolished it. Additionally, dilution of pancreatic juice to 1:10 did not affect antibacterial potency. PMID- 1460327 TI - Fibrinolytic enzymes in ascites during experimental acute pancreatitis in rats. AB - The ascites accumulating during acute pancreatitis contain proteases that play a role in the progression of this disease. The proteases of the fibrinolytic system in the ascites were therefore studied in experimental acute pancreatitis induced in rats. Synthetic substrate assay and the fibrin plate method revealed high activities of proteases, including plasminogen activator, in the ascites. The plasminogen activator had a mol wt of about 50,000 by zymography. The plasminogen activator adsorbed on Lys-sepharose from the ascites was observed at the 100,000 mol wt position and in the 50,000-100,000 mol wt range on zymography and appeared at the 50,000 mol wt position after treatment by concentration. Its activity was enhanced by trypsin treatment. In other experiments, when incubated homogenate of normal pancreas lacking in zymographic activity was injected intraperitoneally into healthy rats, the recovered fluid displayed lytic zones between the 100,00 and 50,000 mol wt positions. These findings suggest that the ascites contained plasminogen activator, part of which was released by intrapancreatic substances and was present in the precursor form. PMID- 1460328 TI - Effects of gastric fundectomy and antrectomy on the exocrine pancreas in the hamster. AB - The effect of gastric fundectomy and antrectomy on growth of the exocrine pancreas was studied in hamsters over 5 and 25 d. Sham-operated animals served as controls. After 5 d, basal plasma gastrin concentrations were significantly increased in fundectomized animals (80.3 +/- 20.6 pmol/L) and significantly decreased in antrectomized animals (11.6 +/- 1.1 pmol/L) as compared with the controls (20.0 +/- 1.7 pmol/L). Similar differences were present among the 25-d groups, whereas basal plasma cholecystokinin (CCK) concentrations did not differ significantly between any groups at any time. At 5 d after fundectomy, there was a significant increase in pancreatic tissue [3H]-thymidine uptake and total DNA content, both of which were reduced 5 d after antrectomy. Autoradiography showed significantly increased [3H]-thymidine labeling index of acinar, intralobular duct, and centroacinar cells of the pancreas at 5 d after fundectomy. The increased intralobular duct cell labeling index persisted 25 d after fundectomy. Labeling indexes after antrectomy did not differ significantly from those in the controls, although antrectomized animals had the lowest values in all three cell compartments at 25 d. At 25 d, pancreatic wet wt and total DNA and protein content were significantly increased after fundectomy and significantly reduced after antrectomy. These findings indicate that fundectomy in the hamster induces pancreatic exocrine tissue hyperplasia and hypertrophy, whereas antrectomy leads to retardation of pancreatic growth. PMID- 1460329 TI - Ductal adenocarcinoma of the pancreas. Histopathological features and prognosis. AB - Between 1972 and 1987, curative surgical resection (RO) was performed in 81 patients with ductal adenocarcinoma of the pancreas. In this study, slides from surgical specimens were reviewed, and histopathological features of the carcinomas were retrospectively reevaluated. Tumor stage was the most important prognostic factor: In UICC stages I, II, and III, the median survival times were 13, 16, and 8 mo, respectively. Lymph node involvement and direct extension of the tumor into adjacent peripancreatic tissue, as well as invasion into peripancreatic organs were found to significantly influence survival. Tumor infiltration of the lymphatic vessels was present in 74% of the resected carcinomas and significantly correlated with survival time. There was no relationship between survival and tumor size; furthermore, histological grade of differentiation, age, and sex had no influence on prognosis. PMID- 1460330 TI - Effects of intraluminal peptide YY on pancreatic function. AB - Peptide YY (PYY) is released postprandially into both the circulation and the distal intestinal lumen. While circulating PYY inhibits pancreatic secretion and insulin release, the effects of intraluminal PYY on pancreatic function are unknown. The aim of the present study was to evaluate the effect of exogenous, intraileal luminal PYY on pancreatic exocrine function and fasting glucose levels. Chronic pancreatic and ileal fistulae (50 cm from the ileocecal valve) were created in nine mongrel dogs. The animals were given intravenous infusions of secretin (125 ng/kg/h) and cholecystokinin octapeptide (CCK-8, 50 ng/kg/h) for four hours. At the beginning of the second hour, either normal saline or PYY, at low [physiologic (2 ng/min)] or high [supraphysiologic (50 ng/min)] levels, was infused antegrade into the ileal fistula for two hours. Pancreatic juice was collected for PYY and glucose levels. Ileal luminal PYY infusions had no effect on pancreatic bicarbonate or protein output. Fasting serum PYY and glucose concentrations were unaffected by either dose of intraluminal PYY. We conclude that ileal luminal PYY does not influence pancreatic exocrine function or fasting glucose levels. PMID- 1460331 TI - Influence of a platelet-activating factor antagonist on severe pancreatitis in two experimental models. AB - This study investigates the role of platelet-activating factor (PAF) in experimental pancreatitis. The concentration of PAF quantified in ascites of bile induced pancreatitis by radioimmunoassay (RIA) ranged from 3.67 +/- 0.39 pmol/mL 2 h to 0.954 +/- 0.39 pmol/mL 10 h after injection of taurocholate. Administration of a potent PAF antagonist, WEB-2170, prior to injection of taurocholate prolonged mean survival time in rats receiving i.v. camostate and albumin (46.4 h, n = 15, vs controls 38.3 h, n = 13). However, the survival rate after 72 h was not improved. The histologically estimated severity of pancreatitis and pancreatic enzymes in blood, tissue, or ascites was not affected. WEB-2170 had no effect on survival when injected simultaneously with taurocholate into the pancreatic duct or given i.v. after induction of pancreatitis (1, 0.1, or 0.01 mg/kg WEB-2170 vs controls). Subcutaneous injection of 10 mg/kg WEB-2170 also did not improve survival in pancreatitis induced by choline-deficient, ethionine-supplemented diet in mice. It is concluded that administration of a PAF antagonist after the onset of severe experimental pancreatitis does not influence its outcome, although activation of PAF may play a role in the pathogenesis of pancreatitis. PMID- 1460332 TI - Isolation of adult pig islet. In vitro assessment and xenotransplantation. AB - This study was conducted to develop an isolation method for adult pig islets and to investigate in vivo function after xenotransplantation as well as in vitro function of isolated islets. From the splenic portion of the glands (n = 20), 3277 +/- 645 islets per gram of pancreas were isolated and recovered by a five step dextran discontinuous density gradient method. Purity of the final preparation obtained from 20 different consecutive pig pancreata was 80-90%. In vitro incubation study revealed a significant insulin release from isolated adult pig islets in response to glucose stimulation. In vitro perifusion study demonstrated a biphasic insulin response to glucose stimulation from isolated islets. Xenotransplantation of approx 2000 isolated adult pig islets into the portal vein of diabetic Wistar rats (n = 8) significantly reduced serum glucose levels from 431 +/- 24 mg/dL to 173 +/- 18 mg/dL 24 h after transplantation. This study provides a development of an isolation method for adult pig islets and demonstrates that isolated islets are viable and functioning both in vitro study and in vivo study of xenotransplantation. PMID- 1460333 TI - Solitary true cyst of the pancreas in an adult. AB - A 35-yr-old woman was presented to the hospital because of nausea 20-30 min after eating, associated with weight loss. A CT scan revealed a cystic lesion in the neck of the pancreas. At operation, a 3-cm diameter cyst was excised from the pancreas. Endoscopic retrograde pancreatography (ERP) was used intraoperatively to identify the transected pancreatic duct, after which a Roux-Y pancreaticojejunostomy was performed. Histologically, the cyst proved to be unilocular and was lined with cuboidal epithelium. The natural history of this lesion is unknown as only four previous case reports of unilocular true cysts in adults have been reported in the English literature. These are reviewed. PMID- 1460334 TI - Submandibular gland as a site for islet transplantation. AB - Homologous transplantation of islets of Langerhans into the submandibular glands of Syrian hamsters was successful in 8 out of 10 recipients. The technique was simple and led to formation of islets of various sizes within the parenchyma of the gland. The morphology and endocrine cell patterns of this islets were identical to pancreatic islets. The advantage of this model for islet transplantation is discussed. PMID- 1460335 TI - [Calpain and calpastatin--structure and function]. PMID- 1460336 TI - [Parental imprinting of mammalian genomes]. PMID- 1460337 TI - [Stress response and stress proteins]. PMID- 1460338 TI - [Snake venom metalloproteinase family: their domain structures and functions]. PMID- 1460339 TI - [The Src homology regions 2 and 3, mysterious associates with protein tyrosine kinases]. PMID- 1460340 TI - [Vesicular transport between Golgi cisternae]. PMID- 1460341 TI - [Small GTP-binding proteins--mode of activation and function]. PMID- 1460342 TI - [Superoxide dismutases: structure, function and pathological significances]. PMID- 1460343 TI - [Recent progress on band 3 protein]. PMID- 1460344 TI - [Dystrophin--current aspects of its biochemical research]. PMID- 1460345 TI - [Endothelin receptors]. PMID- 1460346 TI - [Mutations in the gene responsible for malignant hyperthermia]. PMID- 1460347 TI - Prevention of venous thromboembolism. European Consensus Statement, 1-5 November 1991, developed at Oakley Court Hotel, Windsor, UK. PMID- 1460348 TI - Detection of deep vein thrombosis with a computerized strain gauge plethysmograph. AB - Forty patients suspected clinically the first episode of deep vein thrombosis (DVT) were studied using a new computerized strain gauge plethysmographic (SGP) system, the Phlebotest. A capacitance mode was used to secure the obtaining of maximum venous filling before deflation in every determination. Following parameters were calculated automatically and instantly: the maximum volume change (V sec), the outflow rate during the first second after deflation (F 1.0), the expelled volume in four seconds (EV 4.0) and the surface area over the curve during the first four seconds after deflation (IND). The eighty lower limbs of the patients were divided into three groups according to the Duplex scanning results: proximal (n = 19), distal (n = 13) and no DVT (n = 48) groups. The diagnostic accuracy of the Phlebotest parameters was determined and compared with that of another widely used SGP system, the Perivein. In this case the maximum volume change and the maximum venous outflow (MVO) were calculated manually. The results of the two systems were compatible. For the detection of proximal DVT, the parameters of venous outflow were better than maximum volume change and the best single parameter was maximum venous outflow: F 1.0 for Phlebotest and MVO for Perivein. The two parameters had a similar sensitivity of 79% when 50 and 27 ml/100 ml/min were used as the lower limits of normal respectively. The best criterion for the diagnosis of proximal DVT was F 1.0 < 50 ml/100 ml/min plus the EV 4.0/V sec ratio < 60%, which had a sensitivity of 90%, specificity of 96% and overall accuracy of 94%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460349 TI - Natural history and evolution of peripheral obstructive arterial disease. AB - The natural history of peripheral arterial occlusive disease is discussed. Severe limb-threatening ischemia is the most serious consequence of chronic arterial occlusive disease. Severe ischemia and amputation can be considered as an endpoint in peripheral vascular disease. Severe limb ischemia is relatively uncommon in isolated aortoiliac disease and this is more than twice in patients with either femoropopliteal or multisegmental disease. Subsequent studies have also demonstrated that both smoking and diabetes are associated with a substantial risk for sudden ischemia. A clear majority of about 50% deaths are caused by associated coronary artery disease, 15% to stroke and 10% to vascular disease in the abdomen. Ankle systolic blood pressure is one of the most significant factors in the progression of peripheral arterial occlusive disease and also for cardiovascular mortality. In the future, men need to know how therapies as exercise, during regimens would influence the most frequent complications besides severe limb ischemia, namely brain infarction and coronary artery disease. PMID- 1460350 TI - The grade of carotid stenosis as a prognostic factor during a 14 years' follow-up in 40 angiographically documented patients with cerebrovascular disease. AB - Forty consecutive patients underwent extracranial arteriography between 1974-1976 because of cerebrovascular disease and were treated nonoperatively. This period was chosen to ensure a sufficiently long follow-up. The treatment selection was made individually by the patient's doctor. Deaths (n = 22) during 14 years of follow-up were caused by cerebrovascular disease in 41%, by coronary heart disease in 27% and other in 32%. The median age of decreased patients (group A) was 60.5 years at the time of arteriography and of patients alive after follow-up (group B) 55.5 years, respectively (p = 0.007). Findings were more severe arteriographically in group A than in group B. Twelve patients had occlusion or > 50% stenosis in the common carotid artery or the internal carotid artery in group A and three in group B (p = 0.014). During follow-up there were 17/22 cerebrovascular events in group A and 8/18 in group B (p = 0.033). Smoking was significantly more common in group A (p = 0.002). When the patients were divided on the basis of haemodynamically significant carotid artery stenosis, patients with significant stenosis (group C) proved to be older than patients with non significant stenosis (group D), 62.0 versus 57.0 years, respectively (p = 0.001). The incidence of cerebrovascular events was equal in these groups. Our data suggest that patients with over 50% carotid stenosis have a poor long term prognosis, associated with age and smoking. PMID- 1460351 TI - Is emergency aorto-superior mesenteric artery by-pass worthwhile? AB - Out of 9 superior mesenteric artery (SMA) revascularizations made in emergency, only an early direct aortic reimplantation was successful. The other cases were bypasses and their failures were due either to shock at revascularization (2 cases), or to thrombosis of a by-pass (4 cases), or to persistent ischemic lesions (2 cases). It is suggested: (1) that late mesenteric revascularization should be excluded and let place to extensive bowel resection, (2) that, in emergency, direct SMA aortic reimplantation is preferable to aorto-SMA by-pass. PMID- 1460352 TI - Correlations among capillaroscopic abnormalities, digital flow and immunologic findings in patients with isolated Raynaud's phenomenon. Can laser Doppler flowmetry help identify a secondary Raynaud phenomenon? AB - Thirty subjects with a diagnosis of isolated Raynaud's phenomenon, according to anamnestic and objective criteria, were cross-evaluated by various methods: laser Doppler flowmetry (LDF) during a standardized cold and rewarming test, nailfold capillaroscopy, immunological and other laboratory parameters, to assess the diagnostic and prognostic significance of each method. Correlations were also assessed among disease duration, capillaroscopic pattern score, quantitative digital flow values and laboratory parameters. Nearly 30% of patients showed immunologic abnormalities (ANA positivity at variable titres, ENA, hypocomplementemia, immunocomplexes); 16% of patients had a pathologic capillaroscopic pattern, not well correlated with immunologic findings; a characteristic cold stop reaction of digital flow (partial or total) was detected in 86% of the subjects; in ANA+ pts., ANA titers were positively correlated with the intensity and length of stop reaction (Trec). A significant correlation between digital flow parameters and the capillaroscopic score was also found in each considered group. Our results outline the relevance of LDF, during a standardized thermic test, to evaluate apparently primary RP, because even if a definite scleroderma-like capillaroscopic pattern is absent, this flowmetric method may detect potentially secondary RP patients. PMID- 1460353 TI - Renal artery stenosis in patients with peripheral vascular disease and its correlation to hypertension. A retrospective study. AB - To estimate the frequency of renal artery stenosis, and to detect the correlation between renal artery stenosis and hypertension, 450 consecutive patients with peripheral vascular disease (PVD) were selected. All subjects had undergone aorto femoral conventional angiography. For a possible association with renal artery stenosis, risk factors, clinical and angiographical variables were evaluated e.g.: age, sex, diabetes mellitus, smoking habits, use of antihypertensive drugs, serum creatinine, serum cholesterol, ECG pathology, side of the renal artery lesion, bilateral stenoses, post-stenotic dilatation, number of renal arteries, aortic atherosclerosis, size of the kidneys and angiography induced renal dysfunction. Renal artery stenosis (RAS) was found in 49.1%, 117 patients had a moderate and 104 had a severe stenosis. Of the 221 patients with a renal artery lesion, 44 were normotensive, 177 hypertensive. Hypertension was significantly correlated to RAS. An association was also found for age over 70 years, smoking and pathologic ECG. It is concluded that renal artery stenosis is very common in a population with peripheral vascular disease, and the results achieved from this study makes it worthwhile to identify possible functional markers in a prospective study. PMID- 1460354 TI - Medical treatment of critical limb ischaemia: encouraging results if candidates selected early, therapy based on physiological principles and long-term control established. AB - Medical therapy of CLI is only indicated in patients unsuitable for vascular reconstruction or angioplasty. The approach includes early detection of subjects at risk, observation of physiological principles of therapy and long-term control. The finding of ankle pressure < or = 50 mmHg is of particular value in early detection because of high specificity with respect to CLI. Limb dependency increases skin flow in CLI while in patients with moderate ischaemia vasoconstriction occurs. Positioning of the limb thus contributes to therapeutical effect. Vasodilator substances increase foot blood flow only when administered to patients covered with blankets; improper administration may cause vasoconstriction. When a long-term control programme is established, the number of episodes of CLI decreases as compared to spontaneous course of disease. Rational use of available methods in early diagnosis and therapy considerably improves the prognosis of CLI. PMID- 1460355 TI - Walk training and drug treatment in patients with peripheral arterial occlusive disease stage II. A review. AB - On the basis of the present studies physical therapy is the most effective basis therapy of peripheral arterial occlusive disease stage II according to Fontaine. The consequent integration of the patients into widespread vascular training groups would be desirable. All present studies with so-called vasoactive drugs led to a statistically significant increase in pain-free walking distance. This is especially true for the substances naftidrofuryl, pentoxifylline, and buflomedil. Nevertheless, these studies do not fully meet the standards set by the GCP or the FDA guidelines. It must also be said that the increase in walking distance by vasoactive substances is less pronounced than the effect obtained by walk training alone. Both the vasoactive therapy and controlled walk training aim at an increase in pain-free walking distance. It is, however, still unclear whether the modes of therapy described influence the primary disease. Angiographically controlled studies are momentarily not available. PMID- 1460356 TI - Preliminary results of a complete study protocol on synthetic vascular graft healing and its complications. AB - The microscopic and anatomic features and bacteriologic culture results of different portions of single, explanted dacron synthetic vascular grafts (SVG) were studied together with patient clinical data. With this complete study protocol a better understanding of the healing process and its associated pathology can be achieved. We studied three, amply distanced graft portions from each of five patients (15 total graft portions) undergoing revision for infectious and non-infectious reasons. We divided the SVG portions studied into a Group 1, with high degrees of graft healing and into a Group 2, with both infection-dependent, early healing complications and perigraft chronic inflammatory reaction-dependent, late healing complications. These late healing complications were found dependent upon a host vs graft reaction. This study confirmed in humans the important role of an internal and external fibrotic graft incorporation in the definitive healing of a SVG. A host vs graft reaction was suggested to be an alternative to the frequently cited low virulent infection pathogenesis of late SVG healing complications. A sure definition and treatment of late SVG healing complications will only be established by means of a complete study protocol performed on a large number of explanted SVGs. PMID- 1460357 TI - Prevalence of risk factors in patients with peripheral arterial disease. A clinical and epidemiological evaluation. AB - The aim of this study was to evaluate the prevalence of arterial hypertension and other risk factors in patients suffering from peripheral arterial disease (PAD) in two clinical samples (1.: 102 patients with PAD 69 M, 33 F, studied in our angiology laboratory, matched for sex and age with 102 healthy volunteers; 2.: 184 hospitalized patients, 80 M, 104 F, mean age 57.2 +/- 10.8, with PAD) and in two epidemiological cohorts (1.: Trabia Study, 835 subjects; 2.: Casteldaccia Study, 723 subjects). All patients were subjected to a full clinical and laboratory examination, including the determination of the ankle/arm pressure ratio (Winsor index, positive for PAD when lower than 0.95). In the first clinical study we observed a significantly (p < 0.01) greater prevalence of arterial hypertension (51.9 vs 9.8%), hypercholesterolemia (48.2 vs 21.6%), hypertriglyceridemia (53.7 vs 26.1%), smoking habit (64.3 vs 44.2%), and hyperglycemia (26 vs 7,9%) in PAD patients than in controls. In the second clinical study considering separately the patients under and over 65 years, all risk factors resulted to be more prevalent in younger people than in the aged, except for diabetes and hypertension. In our epidemiological experience, the prevalence of PAD increases with aging, above all in males. In the Trabia Study the risk factors, more associated with PAD, were hypercholesterolemia, smoking and obesity (41.18%) in males and hypertension and hypercholesterolemia (33.3%) and obesity (25%) in females. In the Casteldaccia Study the most important risk factors were smoking (64.28%), hypercholesterolemia (42.86%) and hypertriglyceridemia (35.71%) in males, and obesity (60%), hypercholesterolemia (30%) and diabetes (20%) in females. Cholesterol levels and smoking were significantly higher in PAD patients than in the general population, whereas hypertriglyceridemia and glycemia were not. Arterial hypertension was significantly associated with PAD in the Trabia but not in the Casteldaccia Study. Obesity was significantly associated to PAD in females in both studies. In the Casteldaccia Study, lower HDL-cholesterol levels were observed in PAD patients, above all in males, whereas significantly greater Apo-B values and lower Apo-A1 levels (in males) were shown. The different levels of associated risk factors and their prevalence in PAD patients confirm the multifactorial pathogenesis of atherosclerosis. The exact role of each risk factor in the genesis of PAD is difficult to be evaluated due to the complex biological and statistical interrelationships among different risk factors. However, the management of associated risk factors may favourably influence the risk profile in each patient suffering from PAD. PMID- 1460358 TI - Peripheral vascular disease in newly diagnosed non-insulin-dependent diabetic. AB - The aim of this study was to assess the prevalence of peripheral vascular disease (PVD) in newly diagnosed diabetic patients and the possible relationship to various risk factors. One hundred and twenty non-insulin-dependent diabetics (NIDDs) aged 50-70 years and 93 non-diabetic subjects, matched for age and sex, were studied using Doppler ultrasound. None had a history of alcoholic abuse, while 12 diabetic and 8 non-diabetic subjects were smokers. There were 6 male subjects with PVD (5 NIDDs, 1 control subject) and 2 female diabetic subjects with PVD (p: No SD). In group of male diabetics with PVD, HDL-C levels were found to be lower and triglyceride levels higher, than in those without diabetes, but the difference was not significant. Hypertension, body mass index and smoking were not associated with the presence of PVD in either female or male diabetic subjects. It is concluded that, although PVD tended to be more common in men with newly diagnosed diabetes, the overall findings support the view that macrovascular disease is related to duration of diabetes. PMID- 1460360 TI - [Immunological and cytogenetic studies on early spontaneous abortions]. AB - To reveal the role of maternal immunological mechanisms in early spontaneous abortions, the blocking effect (BE) of the maternal serum was evaluated in a mixed lymphocyte culture, and the chromosome constitution of the abortuses was examined. 1) The mean BE in non-pregnant women as a control (n = 7) was 0.86%. 2) The mean BE in women with an uneventful course of pregnancy (n = 21) was 24.1%, which was significantly higher than that in the non-pregnant women (p < 0.01). 3) Seventeen of the 36 abortuses (47.2%) were chromosomally abnormal. 4) The mean BE among all the patients with spontaneous abortions (n = 36) was -9.8%, which was significantly lower than that in the pregnant women (p < 0.01). However, no difference in mean BE was observed between the patients with chromosomally normal (-8.4%) and abnormal abortuses (-11.2%). 5) In addition, no difference in mean BE was observed between the patients with an abortus with a positive fetal heart beat and the patients with an abortus with a negative fetal heart beat. These results indicate that the decreased BE observed in patients with early spontaneous abortion is a consequence of abortion rather than the cause of abortion. PMID- 1460359 TI - Venous thromboangiitis associated with regional enteritis. AB - Thromboembolic complications occurring in patients with Crohn's disease are increasingly reported and are associated with a high mortality. The mechanism by which the thrombogenic process occurs is unclear. As recent findings suggest that Crohn's disease is a chronic vasculitis with multifocal gastrointestinal infarctions secondary to an imbalance of the cellular hemostatic pathway, extradigestive thrombotic complications might be mediated by the same vascular immune reaction. We report an unusual case of recurrent venous thrombosis associated with regional enteritis, the main point of interest being two-fold: first, this case provides a morphological evidence for an angiitic process as the cause of extradigestive thrombosis; second, the gastrointestinal disease remained subclinical for more than four years although the patient developed major venous thrombotic complications. PMID- 1460361 TI - [Urinary calcium excretion as an early prediction marker for pregnancy induced hypertension]. AB - Two hundred and forty-nine healthy women at 36 weeks gestation and 38 women with pregnancy induced hypertension (PIH) underwent urinalysis for urinary calcium excretion to obtain the calcium/creatinine ratio. This ratio was significantly lower in the women with PIH than in the healthy pregnant women, and it was especially low in those with PIH who had no family history of hypertension. Three hundred forty-eight healthy women at 20 weeks of gestation underwent urinalysis to determine their calcium/creatinine ratio as a means to predict PIH in patients showing no symptoms. In the primiparous group with no family history 58% of the patients with a low calcium/creatine ratio eventually developed PIH. Using a receiver operator curve, we calculated a predictive threshold calcium value for PIH of 0.06 at six month's pregnancy. Thus urinary calcium excretion may be a useful early marker for PIH. PMID- 1460363 TI - [Screening for gestational diabetes mellitus based on blood glucose 2hrs value after a 75g oral glucose load]. AB - We examined the relationship between the time of blood collection and the blood glucose value by analyzing blood glucose values around one hour and two hours after a 75g oral glucose load in 50 women who were at 24 to 28 weeks of gestation. We performed a 75g, 2hrs screening test at 16 to 33 weeks of gestation on all 2,570 pregnant women who visited our out patient clinic between May, 1986 and August, 1991. 1. During the 50-70 minutes after glucose loading, the blood glucose level changed 15-20mg/dl every 10 minutes. During the 110-130 minutes after glucose loading, the change was smaller (10-15mg/dl). These results suggest that the blood glucose level is more stable at 120 minutes than at 60 minutes. 2. When the cut-off point was set at 130mg/dl, the screening test for GDM with a 75g, 2hrs value had a sensitivity of 100%, and a specificity of 85.5% and the incidence of GDM was 3.1%. A 75g, 2hrs screening test therefore seems to be as useful in detecting GDM as a 50g, 1-hour test and to be more suited to crowded out patient clinics because its ability to detect GDM is not seriously affected by small variations in the blood sampling time. PMID- 1460362 TI - [Clinical significance of serum CA130 level in women with spontaneous abortion, hydatidiform mole and early normal and tubal pregnancy]. AB - We examined the serum CA130 level in women in early pregnancy with normal (n = 13), and abnormal (n = 28) course. The abnormal course consisted of intrauterine spontaneous abortion (n = 10), hydatidiform mole (n = 3) and tubal pregnancy (n = 15). The serum CA130 level was higher than for normal nonpregnant women (35u/ml) in 69% (9/13) of women with normal pregnancy, 90% (9/10) of those with intrauterine spontaneous abortion and 100% (3/3) of those with hydatidiform mole; the mean value and standard deviation for these three groups were 131 +/- 150u/ml (n = 13), 197 +/- 253u/ml (n = 10), and 47 +/- 15u/ml (n = 3), respectively. In contrast, the serum CA130 level of the 15 women with tubal pregnancy was 28 +/- 21u/ml. Among these patients, all of the 13 women without genital bleeding had a CA130 level within the normal range for nonpregnant women (mean +/- SD; 20 +/- 6u/ml). Since CA130 is abundant in the decidual tissue but is scant in tubal tissue, a high CA130 level in maternal sera during early pregnancy may indicate the presence of the destruction of decidual tissue, while a low or normal CA130 level throughout early pregnancy is regarded as characteristic of tubal pregnancy. PMID- 1460364 TI - [Influences of magnesium sulfate on maternal calcium metabolism in preterm labor]. AB - The effects of intravenous magnesium sulfate tocolysis on calcium metabolism were studied in 10 patients with preterm labor. A loading dose of magnesium sulfate (4g) was administered intravenously maintenance intravenous infusion of magnesium sulfate (1g per hour). All patients simultaneously received 50 micrograms ritodrin per minutes by intravenous infusion. Serum magnesium increased from 1.91 +/- 0.06mg/dl to 4.6 +/- 0.71mg/dl at 30 minutes (p < 0.01) and it remained relatively high. The fall in serum calcium corrected by serum total protein was most rapid during the first 30 minutes, from 9.04 +/- 0.47mg/dl to 8.3 +/- 0.27mg/dl (p < 0.01). Urinary excretion of magnesium, represented as the calcium/creatinine ratio, rose markedly from 0.05 +/- 0.01 to 3.18 +/- 0.8 at an hour (p < 0.01) and thereafter remained higher than the baseline level. Changes in urinary excretion of calcium paralleled those of urinary evcretion of magnesium. Serum parathyroid hormone rose from 118 +/- 42.2pg/ml to 294 +/- 121pg/ml at 6 hours (p < 0.05). Serum 1 alpha,25-(OH)2D3-rose from 89.3 +/- 44.2pg/ml to 126 +/- 38.7pg/ml (p < 0.05). Serum calcitonin showed no significant change. These findings indicate that correction of hypocalcemia mainly depends on secretion of parathyroid hormone in the early stage, and thereafter depends on the cooperative action of parathyroid hormone and 1 alpha,25-(OH)2D3. PMID- 1460365 TI - [A case of congenital laryngeal atresia with hydrops fetalis]. PMID- 1460366 TI - [A case report of ovarian cancer stage Ia with micrometastasis of para-aortic lymph node]. PMID- 1460367 TI - [Two cases of twin pregnancy with complete hydatidiform mole and coexistent fetus]. PMID- 1460368 TI - [Prenatal sonographic findings of branchial cleft cyst]. PMID- 1460369 TI - [A clinicopathologic study on adnexal tumor after prior hysterectomy]. PMID- 1460370 TI - [Usefulness of fat saturation technique for diagnosing small endometrial implant]. PMID- 1460371 TI - [Perforated internal endometrial cyst, a case report]. PMID- 1460372 TI - [Etiological considerations of the loose shoulder from a biochemical point of view--biochemical studies on collagen from deltoid and pectoral muscles and skin]. AB - In order to elucidate the etiology of the loose shoulder, biochemical characteristics of deltoid and major pectoral muscles and skin collagen from patients with loose shoulder have been investigated. Amounts of soluble collagen, reducible cross-links of collagen and their precursors in both muscles and skin from the loose shoulder were found to be higher than those in the control. These data suggest that soft tissues, especially deltoid muscles, of patients with loose shoulder contain relatively immature collagen fibers compared with normal shoulders. In re-operation cases of the loose shoulder, the collagen fibers in skin were more immature, which may reflect the clinical features of the disease. PMID- 1460373 TI - [An experimental study on tissue induction in anterior cruciate ligament reconstruction with the scaffold-type polyester artificial ligament (Leeds Keio)]. AB - The effect of experimental autogenous tissue implantation (infrapatellar fat pad, fascia lata) together with scaffold type artificial ligament (Leeds-Keio) in ACL reconstruction was studied in 56 mongrel adult dogs. Specimens were examined macroscopically, histologically and by means of microangiography. The results were compared with those in which the artificial ligament was used alone. When infrapatellar fat pad was transferred on artificial ligament, tissue induction was observed 2 weeks after reconstruction. When ACL was reconstructed using a combination of artificial ligament and a small piece of fascia lata, maturated dense collagen fibers were observed 24 weeks after reconstruction. These results indicated that quicker tissue induction could be obtained in ACL reconstruction using an artificial ligament together with a infrapatellar fat pad, and that collagen fiber maturation was accelerated when ACL was reconstructed using an artificial ligament together with a small piece of fascia lata. PMID- 1460374 TI - [Experimental study on the stability of cementless porous coated endoprosthesis]. AB - This study investigated cementless fixation of titanium porous coated endoprosthesis using canine weight-bearing model. Though immature and thin, ingrown trabeculae reached the deepest region of porous coating four weeks after implantation, and gradually matured and thickened thereafter. Pull-out tests of the porous stem at eight weeks showed excellent fixation with average ultimate pull-out force of 142 kgf and average ultimate shear strength of 2.6 GPa. Bone ingrowth rate gradually increased at the proximal and distal region of the stem and, conversely, it gradually decreased at the middle level, suggesting the dependence of bone ingrowth upon the distribution of the amount of stress transferred from implant to the femur. Severe bone remodeling was found on some specimens in which stress transfer was not physiological. Porous coated femoral stems achieve excellent fixation by bone ingrowth, but require physiological stress transfer in order to avoid significant bone remodeling after implantation. PMID- 1460375 TI - [A histo-morphometric study on peripheral nerve allografts in rats with cyclosporin A]. AB - This investigation evaluates regeneration across peripheral nerve allografts in minor mismatch rats immunosuppressed with Cyclosporin A (CSA). Lewis(RT1(1)) rats were recipients of 20 mm sciatic nerve grafts from allogenic Fischer (RT1(1)) donors. The recipients were randomly allocated to CSA immunosuppressed or untreated groups. CSA was administered at a daily dose of 5 mg/kg by subcutaneous injection for 8 weeks. Two animals from each group were sacrificed at 2, 4, 6, 8 and 12 weeks after the operation, and bilateral sciatic nerves were resected. Until the 8th week, the CSA-treated group showed good vascularization and minimal scar formation. The regeneration was faster and better in the CSA-treated group than in the untreated group. At the 12th week, however, the CSA-treated group showed scarring in the grafted nerves and Wallerian degeneration in the distal nerves, whereas the untreated group showed increased vascularization and myelinated fibers. The results have demonstrated that CSA greatly facilitates the regeneration process across the nerve allograft whereas the discontinuation of CSA leads to reduction of the regenerated nerve fibers. These findings would indicate that the use of CSA is imperatively needed even in minor mismatch cases. PMID- 1460376 TI - Effects of catechol compound administration on nerve growth factor synthesis in the peripheral nervous system. AB - The effects of the intraperitoneal administration of catechol compounds on nerve growth factor (NGF) synthesis in the peripheral nervous system were examined in Wistar male rats. Five injections of 4-methylcatechol (4-MC) during a three-day period caused a threefold to fourfold increase in the NGF content of organs with sympathetic innervation (heart, submandibular gland) and the sciatic nerve. Next, we investigated time-dependent changes in the NGF content after a single injection of 2 micrograms of 4-MC. A transient increase in the NGF content was detected in the heart and submandibular gland at 16 hours after administration. In the sciatic nerve, a transient increase in the NGF content was noted at 20 hours in the nerve segments on the distal side, and at 24 hours in the segments on the proximal side. In the superior cervical ganglion and dorsal root ganglion, i.e., the locations of the sympathetic and sensory nerve cell bodies, an increase in the NGF content was detected between 32 and 40 hours. Therefore, catechol compounds stimulate NGF synthesis in the peripheral nervous system, and NGF induced by 4-MC is transported retrogradely in the axon to the soma in a physiological manner. Furthermore, in the dorsal root ganglion and superior cervical ganglion, the use of substance P and tyrosine hydroxylase activity as biochemical markers of sensory and sympathetic neurons has demonstrated the biological activity of newly-synthesized NGF induced by catechol compounds. PMID- 1460377 TI - [An experimental study on direct nerve implantation into denervated muscle--the functional recovery and the site of implantation]. AB - The functional recovery of the newly formed endplates in the muscle reinnervated by direct neurotization was studied grossly, electrophysiologically and histologically in the anterior tibialis muscle of rats. The proximal stump of the tibial nerve was severed at the ankle level and was embedded at the level of distal one fifth of the muscle where no endplates were detected just after denervation of the muscle. Histologically, the accumulations of acetylcholinesterase activity were detected 4 weeks after neurotization. Electrophysiological study using a multi-channel electrode revealed the two directional propagation of action potentials 8 weeks after neurotization, and the propagation started from no other sites than the nerve-implantation. The muscle tension revealed 42% of the contralateral muscle 52 weeks after neurotization. These results concluded that the function of the newly formed endplates spread throughout the muscle and it was lasting. PMID- 1460378 TI - [Experimental study on the spinal lesions in hyperostotic mouse (twy/twy): special reference to the pathogenesis of the ossification of the spinal ligaments and to the action of ethane-1-hydroxy-1, 1-diphosphonate (EHDP)]. AB - The hyperostotic changes in the spine of the twy mouse and the action of ethane-1 hydroxy-1, 1-diphosphonate (EHDP) on those hyperostotic changes were studied histomorphometrically. The periosteal bone formation and the endosteal bone resorption in the anterior cortex of the vertebral bodies of the twy mouse continued even after maturation, resulting in the anterior cortex shifting to the anterior direction. In parallel with these changes, calcification in the enthesis (to which spinal ligaments and the outer layer of disc fibrosis are attached) continued, ending in ankylosis of the whole spine. It was similar to a membranous ossification. Moreover calcification in these regions was most sensitively inhibited by EHDP and reappeared as soon as the discontinuation of EHDP. These findings showed that the pathogenesis of the twy mouse was the hyperostosis which continued even after maturation in the genetical region of a membranous ossification, especially in the enthesis. Further they appeared to be similar to the initial changes in ankylosing spinal hyperostosis or the ossification of the spinal ligaments. In addition, our results provided evidence for the usefulness of EHDP in the twy mouse. PMID- 1460379 TI - [Osteoarthropathy due to amyloid deposition in chronic renal dialysis patients]. PMID- 1460380 TI - [Labor accidents and industrial physicians--from the standpoint of orthopaedist]. PMID- 1460381 TI - [Radiological changes in the femoral side after cementless total hip arthroplasty]. AB - We investigated radiological and functional changes of the femurs with cementless total hip arthroplasty. Our particular attention was paid to the relationship between the thigh pain and the rate, period of its incidence and the progression of radiological changes. The cases studied consisted of 57 female patients with severe coxarthrosis who were implanted with a SUS316-L macroanchoring type of THP (JIAT). Clinical evaluations, radiographic findings in the femoral side, and osteometric observations were carried out periodically in the period before surgery until five years after surgery. The JOA criterion at the time of the final examination was average 91 points. However, we observed a high degree of bone change in the femur on the radiogram. Of 63 hips, there was 71% cortical bone atrophy, a 43% reduction of cortex thickness, 25% cortical bone hypertrophy, 94% endosteal bone bridging in the stem tip, a 64% linear sclerosis of the neighboring stem, and a 37% enlargement of the medullary cavity. Bone atrophy was manifested soon after surgery, and there was 34% recovery. Further, there was no connection between thigh pain and bone changes. We, therefore, concluded that such bone changes as atrophy would not immediately bring about adverse consequences. PMID- 1460383 TI - An evaluation of the discrepancy definition of dyslexia. AB - The purpose of this study was to determine whether children with dyslexia, that is, children whose reading levels were significantly lower than would be predicted by their IQ scores, constituted a distinctive group when compared with poor readers, that is, children whose reading scores were consistent with their IQ scores. The performance of children with dyslexia, poor readers, and normally achieving readers was compared on a variety of reading, spelling, phonological processing, language, and memory tasks. Although the children with dyslexia had significantly higher IQ scores than the poor readers, these two groups did not differ in their performance on reading, spelling, phonological processing, or most of the language and memory tasks. In all cases, the performance of both reading disabled groups was significantly below that of nondisabled readers. The findings were similar whether absolute difference or regression scores were used. Reading disabled children, whether or not their reading is significantly below the level predicted by their IQ scores, experience significant problems in phonological processing, short-term and working memory, and syntactic awareness. On the basis of these data, there does not seem to be a need to differentiate between individuals with dyslexia and poor readers. Both of these groups are reading disabled and have deficits in phonological processing, verbal memory, and syntactic awareness. PMID- 1460382 TI - Tissue reactions at the implant-bone interface of the cementless total knee prostheses with sinking (Okayama University Mark-II type). AB - Periprosthetic tissues of 14 revised knees of 11 patients, who had undergone Mark II type cementless total knee prosthesis, were examined to find the relationship between tissue and sinking. Nine patients had rheumatoid arthritis and two had osteoarthritis. Two types of tissue reactions were observed at the implant-bone interface: 1) granulation-dominant tissue, composed of giant cells and macrophages phagocytizing high density polyethylene flakes and dense granules of metal, on the femoral side in six cases, and tibial side in four, 2) fibrosis dominant tissue on the tibial side in seven, and femoral side in four. On each type, three zones were observed. In the deep zone adjacent to the bone, hyaline cartilage-like tissue was located on the tibial side in four cases, and femoral side in one. An immunohistochemical stain with S-100 proteins and transmission electron microscopy revealed chondrocyte-like features. Chondrogenesis was more frequently observed on the tibial side. PMID- 1460384 TI - Academic achievement following childhood brain disease: implications for the concept of learning disabilities. AB - The present study examined three hypotheses regarding the consequences of early brain damage for academic achievement: First, early brain insults will have a negative impact on achievement, even in children with normal intelligence. Second, underachievement in these children will be at least partially independent of IQ (i.e., not fully accounted for by a lowering of IQ within the average range). Third, normally intelligent children with histories of brain insult will also manifest selective cognitive dysfunctions. To test these hypotheses, we compared two groups of children who had recovered from Haemophilus influenzae type b meningitis. The "complicated" group consisted of children who, as a consequence of having sustained neurologic complications during their illness, were more likely to have had brain insults. Children in the "uncomplicated" group did not have complications with their illness and were regarded as having escaped significant central nervous system (CNS) pathology. Only children with normal hearing and a prorated Full Scale IQ of at least 80 (WISC-R) were considered. Group differences on the Wide Range Achievement Test-Revised were consistent with the first two hypotheses. Although the two groups had similar Verbal IQs, the complicated group also had a lower mean Performance IQ and performed less well on perceptually demanding neuropsychological tasks. Findings suggest that learning disabilities may have selective, brain-related cognitive antecedents; but they challenge the practice of using IQ criteria for clinical diagnosis. PMID- 1460386 TI - Minor neurological dysfunction is more closely related to learning difficulties than to behavioral problems. AB - In a group of 570 nine-year-old children (315 boys and 255 girls) without an overtly handicapping neurological condition, relationships were studied between the presence of minor neurological dysfunction (MND) on the one hand and cognitive and behavioral problems on the other hand. The aim of the study was to investigate whether MND was more closely related to learning problems than to behavioral difficulties. The group was a subpopulation of the birth cohort of the Groningen Perinatal Project in the Netherlands, in which perinatal developmental relationships are studied. The age-specific and standardized neurological examination technique of Touwen (1979) was used, resulting in a description of the neurological condition in terms of the number of deviant clusters. The absence of deviant clusters indicated a normal neurological condition (n = 418); children with one or two deviant clusters were classified as MND-1 (n = 86) and those with more than two deviant clusters as MND-2 (n = 66). The presence and severity of MND was significantly related to poor performance on standardized reading, spelling, and arithmetic tests. MND was also related to ratings of distractible behavior on parent and teacher questionnaires, but to a lesser extent than the cognitive problems. Ratings of so-called "troublesome" and "timid" behavior were not related to MND. Our conclusion is that learning problems are more closely related to MND than are behavioral difficulties. This has implications for prevention and intervention: In the former the focus should be more on biological hazards, in the latter on environment and rearing attitudes. PMID- 1460385 TI - Discrepancy compared to low achievement definitions of reading disability: results from the Connecticut Longitudinal Study. AB - We used data derived from a survey sample, the Connecticut Longitudinal Study (CLS), to compare two commonly employed definitions of reading disability: a discrepancy-based model (D) and a low reading achievement model (L). We identified children satisfying each definition in second grade and compared the groups retrospectively in kindergarten and prospectively in fifth grade using parent-based, teacher-based, and child-based measures. Our findings suggest more similarities than differences between the reading disabled groups. The most salient differences were those related to ability and seem inherent in the definitions of the groups: Children identified as D have significantly higher verbal, performance, and full scale IQ scores than those identified as L. These findings suggest that both groups of children with reading disability, that is, those defined by either D or L, should be considered eligible for special education services. PMID- 1460387 TI - Comparison of visual-spatial performance strategy training in children with Turner syndrome and learning disabilities. AB - This study examined the effects of a verbal mediation strategy on three groups of subjects who had visual-spatial deficits. Thirteen females with Turner syndrome, 13 females with nonverbal learning disabilities, and 14 males with nonverbal learning disabilities, who ranged in age from 7 to 14 years, were taught via a cognitive behavioral modification approach to verbally mediate a spatial matching task. Pretest and posttest performance differences on parallel forms of a visual spatial orientation task were examined. All three groups showed significant improvement in visual-spatial task performance after the training. There were no significant differences in the degree of improvement among the three groups. The results suggest that children with Turner syndrome may benefit from problem solving strategy training in a manner similar to children with nonverbal learning disabilities. PMID- 1460388 TI - Undergraduate admission policies, practices, and procedures for applicants with learning disabilities. AB - This study examined (a) the academic and nonacademic criteria used by admission personnel to determine the eligibility of undergraduate applicants with learning disabilities, (b) agreement of criteria used by institutions of varying competitiveness, and (c) the frequency with which admission personnel conduct validity studies on these criteria. A nonrandom sample consisting of 66 state universities and colleges in the Northeast was surveyed. The results suggest that the academic and nonacademic criteria employed are similar to those employed for applicants without learning disabilities, the criteria used by different types of institutions differ significantly, and admission personnel do not conduct validity studies. Further clarification and validation of admission criteria appears warranted. PMID- 1460389 TI - Similarities in the social competencies of learning disabled and low achieving elementary school children. AB - This study sought to examine distinctions in social competencies between children with learning disabilities (LD) and other children who also experience academic difficulties. Eighty-five children with LD (54 male, 31 female) in Grades 3 through 6 from a large urban school district were compared to a group of low achieving (LA) peers matched on achievement as well as sex, race, and grade. The samples were 42% black, 39% Hispanic, and 19% Anglo. Both groups completed two self-concept questionnaires, a loneliness scale, and a measure of their social relationships outside of school. In addition, their classmates completed a peer rating scale and their teachers completed two ratings of the child's social skills. The results indicated that children with LD and LA children were comparable on most measures, although children with LD reported themselves as being less lonely than LA children. In addition, regular-class children rated children with LD as more likable than LA children. The results highlight similarities in the social competencies of children with LD and LA children and suggest that special education classes may offer some social advantages to children with mild handicaps. PMID- 1460390 TI - Students with learning disabilities in the university environment: a study of faculty and student perceptions. AB - This study examines faculty and student perceptions regarding university students with learning disabilities, sensitivity to such students' special needs, accommodations, and the perceived impact of a learning disability. Results reveal a general sensitivity to the special needs of students with learning disabilities; however, group differences suggest several areas warranting further attention. PMID- 1460391 TI - Identifying alterable patterns in employment success for highly successful adults with learning disabilities. AB - Adults with learning disabilities were studied to ascertain the patterns of successful functioning that promoted high levels of vocational success. This area of research has been neglected in the developing research base on adults with learning disabilities. In this study of 46 highly successful and 25 moderately successful adults with learning disabilities using ethnographic interviews, it was found that the overriding theme was control and that control was sought through the pursuit of two sets of themes--internal decisions and external manifestations. These themes transcended the entire sample, and the clear difference between the groups was the degree of attainment on the various elements the themes comprised. These elements and themes are discussed and a model of successful vocational functioning is developed and explained. PMID- 1460392 TI - The neurobiology and neuropsychology of adult learning disorders. AB - The area of adult learning disabilities is reviewed from a neurobiological and neuropsychological perspective. The seminal contributions of Galaburda's neuroanatomic studies, Duffy's neurophysiologic findings, and recent magnetic resonance imaging studies have illustrated various possible pathophysiologic bases in dyslexia and are reviewed along with other neurobehavioral disorders that may coexist with learning disorders. Neuropsychological assessment methods in evaluating learning disabilities are reviewed and test results in a case of traumatically induced dyslexia are compared to those obtained in three adults with residual developmental dyslexia. The problems associated with treatment of adult learning disorders are discussed in the context of brain plasticity and recovery of function from the perspective of a brain-injury model. Lastly, the basis common to neurologic factors subserving learning disability and emotional dysfunction is explored. PMID- 1460393 TI - Adults with learning disabilities: current and future research priorities. AB - This article presents a review of current research, or what is currently known about adults with learning disabilities. The review is organized under different settings, including the community, postsecondary, and employment environments, and is followed by a review of longitudinal studies. Based on the review of the current status of the literature, research priorities for the 1990s are presented, including (a) identifying and conducting research with specific individuals or samples within the adult (LD) population; (b) identifying successful intervention techniques within the cognitive, social, personal, and vocational domains; (c) conducting research in a variety of environments, including community, employment, and postsecondary settings and across critical periods of an individual's lifespan (such as movement from postsecondary environments into employment and from employment to retirement); and (d) examining alternative methodologies, such as single-subject, case study, group research, and so forth, in future investigations. The priorities are followed by a description and comparison of various research methodologies. PMID- 1460394 TI - Learning disabilities in adulthood: personal perspectives. PMID- 1460395 TI - Some thoughts on why the prevalence of learning disabilities has increased. PMID- 1460396 TI - Adoptees among students with disabilities. PMID- 1460397 TI - The relationship of phonological awareness, rapid naming, and verbal memory to severe reading and spelling disability. AB - The present study examined the relationship of phonological awareness, naming speed, and verbal memory to the scores obtained from five tests assessing word attack, word identification, reading comprehension, and spelling skills in 54 children with severe reading disabilities (48 boys and 6 girls; M age = 9 years, 7 months). Multiple regression analyses indicated that the best predictor of achievement across the five academic tests was the Verbal Comprehension factor from the Wechsler Intelligence Scale for Children-Revised. Age, socioeconomic status (SES), and externalizing behavior problems were also significant predictors of achievement, depending on the academic measure. After controlling for age, SES, behavior problems, and intelligence, the phonological awareness task added significantly to the prediction of word attack, spelling, and reading comprehension scores; rapid letter naming added significantly to the prediction of word identification and prose passage speed and accuracy scores; and a word list memory task added significantly to the prediction of word recognition scores. These results suggest that several independent processes interact to determine the extent and severity of reading problems. PMID- 1460398 TI - The perspectives of mothers whose children are in special day classes for learning disabilities. AB - This article presents information about the attitudes and beliefs of mothers concerning their children in learning disabilities classes. Four mothers were interviewed over a 1-year period. Their comments about services provided by educational and mental health professionals indicated high levels of frustration and dissatisfaction. Parental expectations and perspectives differed from those of educators. Participants and educators were found to view learning disabilities differently. PMID- 1460399 TI - Information flow in the hospital: a comparative study of the Hungarian and the Dutch situation using a two axes model of hospital information flow. AB - This study compares the organization and structure of information flow in a Dutch and in a Hungarian hospital. The study was carried out as a field orientation part of a Health Care Management project of the Hogeschool van Amsterdam. The host of the field orientation was the BAZIS Foundation, the Central Development and Support Group Hospital Information System, Leiden. The visited hospitals were equipped with the BAZIS Hospital Information System. The method of study consisted of series of formalized interviews with all-level actors of a hospital; the interpretation of data was enhanced by a two axes (patient and management) model of information flow defined by the authors. In summary, Dutch hospitals show a more elaborate information flow system, with more information flow channels sideways among equal levels, less bureaucracy in organization of information flow, and significantly more benefits of automation, compared to the Hungarian situation. PMID- 1460401 TI - A visual field quantification system for the Goldmann Perimeter. AB - We have developed a visual field quantification system that can accurately quantify the measurement results by the Goldmann Perimeter (GP). This system calculates the plural indexes introduced in published papers. In recent years, several isopter quantification methods have been proposed. In these methods, the isopters are digitized and the data are input into a computer, after which a computer program evaluates the changes in the isopters quantitatively. However, each program is only able to evaluate private indexes. We have developed a system that quantifies data using multiple methods. This system used five methods that have been introduced in published papers. With this system, a physician can analyze GP data with multiple methods and can diagnose diseases accurately. We have already input about 2500 GP recording papers into the computer by this system. We then calculated the plural indexes, and visualized the temporal changes in the perimetry. PMID- 1460400 TI - Standardized nursing language for healthcare information systems. AB - Since a substantial component of health care delivery is reflected in nursing's work, it is imperative that nursing expedites implementation of a standardized language that reflects nursing's work and ultimately allows outcome evaluation. This paper will summarize the state of development and related issues of standardized language in nursing, including: Nursing Minimum Data Set, Taxonomies of Nursing Diagnoses, Nursing Interventions, Outcomes, and the Nursing Management Minimum Data Set. The Nursing Minimum Data Set, including nursing care, patient or client demographic, and service elements, reflects a standardized collection of essential nursing data used by multiple data users in the health care delivery system across all types of settings. The nursing care elements include nursing diagnosis, nursing intervention, nursing outcome, and intensity of nursing care. Currently, more than 100 nursing diagnoses have been accepted for clinical testing by the North American Nursing Diagnosis Association (NANDA) and have been incorporated into a taxonomy of nursing diagnoses that reflects patient responses to actual or potential health problems that nursing can address. A current formulation of a taxonomy of nursing interventions for the treatment of the nursing diagnoses yielded 336 nursing intervention labels organized at three or four levels of abstraction. Concomitant with these endeavors is the necessity for identifying outcomes associated with each diagnosis and its treatment. Concepts and a classification for indicators of these outcomes are being reviewed. Last, to address the contextual covariates of patient outcomes, a collection of core variables needed by nurse managers to make management decisions and compare nursing effectiveness across institutions and geographic regions is under development. In summary, standardized measures to determine cost effective, high quality, appropriate outcomes of nursing care delivered across settings and sites are being developed. PMID- 1460402 TI - The science of medical information systems. PMID- 1460403 TI - The effect of a multiple literature database search--a numerical evaluation in the domain of Japanese life science. AB - In literature database searching, we show that it is necessary to use plural databases for a more improved search. We also compare the results of a single database search with that of multiple database search in the domain of Japanese life sciences. We searched the MEDLINE and EMBASE using the same search terms. There were some differences in the results, owing to differences in the journals and recording methods. We herein show some of the differences in the journals contained in both databases. Furthermore, we show the differences in the number of papers derived from the same journal. Next, as an example of a practical search, we selected some universities in Japan, searched both databases regarding papers published from these universities and then merged the results by hand. According to our results, only 63% of all papers were common to both databases. PMID- 1460404 TI - The prevalence and risk factors of hypertension in population aged 30-65 years in rural area, Amphoe Phon, Khon Kaen. AB - The prevalence of hypertension in a population aged 30-65 years in a rural area in Amphoe Phon, Khon Kaen was 18 per thousand (22 per thousand in males and 16 per thousand in females). The prevalence of isolated systolic hypertension was 5 per thousand (10 per thousand in males and 2 per thousand in females). The risk factors of blood pressure elevation were age, body mass index, level of development of village and non farmer occupation. PMID- 1460405 TI - Liver injuries: a five-year study at Surat-thani Hospital. AB - Most liver injuries can usually be handled by simple technique. In this study, 70 per cent of the cases needed only simple suture. There were 10 cases (16.67%) in which no surgical procedures were required at all, because the bleeding had stopped prior to surgery. Complications and mortality varied according to the type of liver injury, the involved organ injury and the most important factor, shock prior to and during surgery. This study reports not only the type of liver injury, causes, treatment, complications and mortality rate but it also compiles the surgical techniques used in managing liver injury according to severity. PMID- 1460406 TI - Anterior lumbar discectomy: a study of iliac and fibular bone graft. AB - The author studied the iliac and fibular autogenous bone grafts in anterior lumbar discectomy for herniated disc of 29 patients. They were examined 2 1/2 to 8 years postoperatively. Iliac numbness was found in 4 of 15 patients (26.7%) and fibular pain was found in one of 14 patients (7.1%). For functional result, iliac and fibular graft were found excellent in 86.6 and 92.9 per cent respectively. There was no statistically significant difference in proportion of patients experiencing discomfort at donor site or in the functional result between iliac and fibular grafts. PMID- 1460407 TI - A comparative study of isobaric and hyperbaric solution of bupivacaine for spinal anaesthesia in caesarean section. AB - Though hyperbaric solution of bupivacaine following intrathecal injection had satisfactory spread of analgesia, it regressed rapidly with more side effects. Isobaric bupivacaine seemed to provide a slow regression of analgesia with fewer undesirable effects except for its inadequate spread of analgesia. As a result, if the dosages as well as the time of administration of isobaric solution are well adjusted, we believe that it is safe and reliable with an excellent level of analgesia for caesarean section. PMID- 1460408 TI - Treatment of outpatients with community-acquired pneumonia with roxithromycin. PMID- 1460409 TI - In vitro antimicrobial activity of cefodizime, a third generation cephalosporin. AB - Cefodizime is one of the new broad-spectrum cephalosporins. It is an aminothiazolyl iminomethoxy cephalosporin which is metabolically stable and has a prolonged serum half life. Cefodizime was primarily active against gram-negative bacilli and at the concentration of 0.5 mg/L, it inhibited 90 per cent of Enterobacteriaceae. P. mirabilis was the most susceptible species tested (MIC90 of 0.02 mg/L). E.coli, K.pneumoniae, Salmonella spp., Shigella spp. and M. morganii were also very sensitive to cefodizime, with the MIC90 of 0.25-0.5 mg/L. Cefodizime, however, was not active against most gram-negative bacilli possessing Type I beta-lactamases of Richmond and Sykes, namely, Enterobacter spp., P. aeruginosa and A. anitratus (MIC90 of > 128 mg/L). Among gram-positive bacteria, only S.pyogenes was highly susceptible (MIC90 of 0.05 mg/L), while S. aureus (methicillin-sensitive) was moderately susceptible and Enterococcus spp. was resistant. Cefodizime appeared to be bactericidal and was not affected by serum. High inoculum (10(7) cfu/ml) of K.pneumoniae and Enterobacter spp. resulted in increase of the MIC of cefodizime. This study shows that local bacterial isolates in a university hospital in Bangkok, Thailand were not different in susceptibility pattern from those reported in developed countries. The in vitro activity of cefodizime as a third generation cephalosporin, with its good pharmacokinetic property, and the property of the agent as a biological response modifier, should prove that this is a promising new agent in treating serious infections especially in immunosuppressed hosts. PMID- 1460410 TI - HIV infection in male patients attending a sexually transmitted disease clinic. AB - Three hundred and fifty-two heterosexual males, attending a sexually transmitted disease clinic at Siriraj Hospital from December 1989 to February 1991 were studied for the prevalence of HIV infection. Of these, 334 men reported prostitutes as the main source of their sexually transmitted disease. No one had received blood transfusion in the last 5 years, and there was no history of intravenous drug use, homosexuality or bisexuality. HIV antibody was found in the sera of 24 men (6.8%). HIV seropositivity was associated with serologic makers of syphilis (P < 0.05) but was not associated with present genital ulcers on physical examination or other STDs. These data indicate the high rate of female prostitutes to male transmission of HIV infection in the presence of sexually transmitted disease and confirms the relationship between syphilis and HIV infection. HIV/AIDS educational programmes and campaigns to promote condom use among prostitutes and clients are an urgent need in Thailand. PMID- 1460411 TI - Primary lymphoma of the esophagus: a case report. AB - A case of primary non-Hodgkin's lymphoma of the esophagus was reported. The macroscopic manifestation from esophagography, computed tomography and esophagoscopy were demonstrated. Pathological findings were demonstrated. The tumour responded well to combined therapy of surgery, radiotherapy and chemotherapy. PMID- 1460412 TI - Acute cyanide poisoning: a case report with toxicokinetic study. AB - Cyanide poisoning is a life threatening condition. But specific antidotes exist and can be easily prepared from available substances in hospital. Administration of antidotes will produce methemoglobin, which itself causes hypoxia. Nitrite induced methemoglobin can be extremely dangerous and even lethal. Before administering the antidotes, the diagnosis should be confirmed. Nitrite should not be given if the poisoning is mild or diagnosis is uncertain, to avoid excessive methemoglobin, dosage of sodium nitrite must be adjusted according to hemoglobin level (Table 1). Usage of sodium nitrite and sodium thiosulfate in the recommended doses are safe and effective for cyanide poisoning. PMID- 1460413 TI - Granulomatous mastitis: case report and review of literature. AB - A 38-year-old woman presented with a 5-month history of a right breast mass after delivery of her second child. The lesion simulated the picture of a carcinoma on clinical grounds. Fine-needle aspiration also reported an erroneous diagnosis of malignancy. At surgery, a discrete granuloma with microabscesses was seen without any causative organisms being identified. Open biopsy or Tru-Cut needle biopsy is recommended to prevent such an error which may result in unnecessary radical surgery. PMID- 1460414 TI - Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. AB - Serum mannose-binding protein (MBP) is a C-type lectin that binds to terminal mannose and N-acetylglucosamine moieties present on surfaces of certain pathogens and activates the classical complement pathway. In the present study, we describe the mechanism underlying the activation triggered by MBP. The human serum MBP fraction was obtained by sequential affinity chromatography on mannan-Sepharose, anti-IgM-Sepharose and anti-MBP-Sepharose in the presence of calcium ions. This fraction contained a C1s-like serine protease as assessed by C4 consumption. The C1s-like serine protease, designated MBP-associated serine protease (MASP), was separated from MBP by rechromatography on anti-MBP-Sepharose in the presence of ethylenediaminetetraacetic acid. MASP exhibited both C4- and C2-consuming activities. The molecular mass of MASP was estimated to be 83 kD with two polypeptides of heavy (66 kD) and light (L) (31 kD) chains linked by disulfide bonds. The serine residue responsible for protease activity is located on the L chain. Reconstitution experiments using MASP and MBP revealed that combination of the two components restores C4- and C2-activating capacity on mannan. Based on analyses of molecular size, antigenicity, and 11 NH2-terminal amino acid sequences of the L chain, we conclude that MASP is a novel protein different from C1r or C1s. Our findings are not in accord with a proposed mechanism by which MBP utilizes the C1r2-C1s2 complex to initiate the classical complement pathway. PMID- 1460415 TI - Human lymphokine-activated killer cells are cytotoxic against cells infected with Toxoplasma gondii. AB - Experiments were conducted to determine whether human lymphokine-activated killer (LAK) cells are cytotoxic against cells infected with Toxoplasma gondii. Nylon wool nonadherent (NWNA) peripheral blood lymphocytes, as well as purified natural killer cell (NK) (CD3- CD16+ CD56+) and T (CD3+ CD16- CD56-) cells obtained from five healthy T. gondii seronegative volunteers exhibited minimal cytotoxic activity against T. gondii-infected cells. When standard LAK (S-LAK) cell preparations were induced by incubation of NWNA cells with recombinant interleukin 2, induction of remarkable cytotoxic activity against T. gondii infected cells. When standard in LAK cell preparations from each of the volunteers. The phenotype of the LAK precursor and effector cells varied depending on the target cell used. Whereas the precursor and the effector cells of most of the LAK activity against K562 and Daudi cells were cells with NK phenotype, when T. gondii-infected cells were used as targets, both cells with NK and T cell phenotypes were precursors and effectors of the lysis. When cytotoxic activity of S-LAK cells was compared with the activity of adherent LAK (A-LAK) cells, A-LAK cells displayed higher cytotoxic activity against T. gondii-infected cells, as well as against K562 and Daudi cells. Cold target inhibition experiments suggested that there is a subset of LAK effector cells capable of lysing both T. gondii-infected cells and Daudi cells, whereas other subsets preferentially or exclusively lyse one of these target cells. PMID- 1460416 TI - Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. AB - We recently reported the purification of a lymphocyte granule protein called "fragmentin," which was identified as a serine protease with the ability to induce oligonucleosomal DNA fragmentation and apoptosis (Shi, L., R. P. Kraut, R. Aebersold, and A. H. Greenberg. 1992. J. Exp. Med. 175:553). We have now purified two additional proteases with fragmentin activity from lymphocyte granules. The three proteases are of two types; one has the unusual ability to cleave a tripeptide thiobenzyl ester substrate after aspartic acid, similar to murine cytotoxic cell protease I/granzyme B, while two are tryptase-like, preferentially hydrolyzing after arginine, and bear some homology to human T cell granule tryptases, granzyme 3, and Hanukah factor/granzyme A. Using tripeptide chloromethyl ketones, the pattern of inhibition of DNA fragmentation corresponded to the inhibition of peptide hydrolysis. The Asp-ase fragmentin was blocked by aspartic acid-containing tripeptide chloromethyl ketones, while the tryptase fragmentins were inhibited by arginine-containing chloromethyl ketones. The two tryptase fragmentins were slow acting and were partly suppressed by blocking proteins synthesis with cycloheximide in the YAC-1 target cell. In contrast, the Asp-ase fragmentin was fast acting and produced DNA damage in the absence of protein synthesis. Using a panel of unrelated target cells of lymphoma, thymoma, and melanoma origin, distinct patterns of sensitivity to the three fragmentins were observed. Thus, these three granule proteases make up a family of fragmentins that activate DNA fragmentation and apoptosis by acting on unique substrates in different target cells. PMID- 1460417 TI - Comparative clonal analysis of human immunodeficiency virus type 1 (HIV-1) specific CD4+ and CD8+ cytolytic T lymphocytes isolated from seronegative humans immunized with candidate HIV-1 vaccines. AB - The lysis of infected host cells by virus-specific cytolytic T lymphocytes (CTL) is an important factor in host resistance to viral infection. An optimal vaccine against human immunodeficiency virus type 1 (HIV-1) would elicit virus-specific CTL as well as neutralizing antibodies. The induction by a vaccine of HIV-1 specific CD8+ CTL in humans has not been previously reported. In this study, CTL responses were evaluated in HIV-1-seronegative human volunteers participating in a phase I acquired immune deficiency syndrome (AIDS) vaccine trial involving a novel vaccine regimen. Volunteers received an initial immunization with a live recombinant vaccinia virus vector carrying the HIV-1 env gene and a subsequent boost with purified env protein. An exceptionally strong env-specific CTL response was detected in one of two vaccine recipients, while modest but significant env-specific CTL activity was present in the second vaccinee. Cloning of the responding CTL gave both CD4+ and CD8+ env-specific CTL clones, permitting a detailed comparison of critical functional properties of these two types of CTL. In particular, the potential antiviral effects of these CTL were evaluated in an in vitro system involving HIV-1 infection of cultures of normal autologous CD4+ lymphoblasts. At extremely low effector-to-target ratios, vaccine-induced CD8+ CTL clones lysed productively infected cells present within these cultures. When tested for lytic activity against target cells expressing the HIV-1 env gene, CD8+ CTL were 3-10-fold more active on a per cell basis than CD4+ CTL. However, when tested against autologous CD4+ lymphoblasts acutely infected with HIV-1, CD4+ clones lysed a much higher fraction of the target cell population than did CD8+ CTL. CD4+ CTL were shown to recognize not only the infected cells within these acutely infected cultures but also noninfected CD4+ T cells that had passively taken up gp120 shed from infected cells and/or free virions. These results were confirmed in studies in which CD4+ lymphoblasts were exposed to recombinant gp120 and used as targets for gp120-specific CD4+ and CD8+ CTL clones. gp120-pulsed, noninfected targets were lysed in an antigen-specific fashion by CD4+ but not CD8+ CTL clones. Taken together, these observations demonstrate that in an in vitro HIV-1 infection, sufficient amounts of gp120 antigen are produced and shed by infected cells to enable uptake by cells that are not yet infected, resulting in the lysis of these noninfected cells by gp120 specific, CD4+ CTL.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1460418 TI - Glucocorticoids induce the expression of CD8 alpha chains on concanavalin A activated rat CD4+ T cells: induction is inhibited by rat recombinant interleukin 4. AB - Rat T lymphocytes, activated in vitro with concanavalin A (Con A), were shown by flow cytofluorographic analysis to contain a population of cells that simultaneously expressed CD4 and the alpha chain of CD8. The inclusion of the glucocorticoid hormone dexamethasone in the culture medium greatly increased both the frequency of these double-positive cells and the level of CD8 alpha chain expression. The level of expression of CD4 was not affected, and the cells that expressed CD8 antigen only also remained unchanged in surface phenotype. Detailed studies demonstrated unequivocally that the CD4+ CD8 alpha + cells were not artifacts produced by the random association of single-positive cells in the flow cytofluorograph, but arose from precursors that were single-positive CD4+ cells before activation. Furthermore, Con A activation of purified CD4+ T cells, in the presence of T cell-depleted accessory cells, showed that CD8+ T cells played no role in the induction process. However, the induction of CD8 alpha chain expression on CD4+ T cells and the enhancement of this expression by dexamethasone were almost completely inhibited by rat recombinant interleukin 4 (IL-4). Detection of mRNA for rat CD8 alpha chain by Northern blot closely paralleled the cell surface expression of CD8 alpha antigen, indicating that dexamethasone and IL-4 had opposing effects on mRNA levels. In contrast, IL-4 and dexamethasone both induced CD8 alpha chain expression on a rat CD4+ T cell clone when this was activated by specific antigen, and, although the effect with IL-4 was relatively weak, it did not antagonize the effect of the glucocorticoid. The possible significance of these results is briefly discussed. PMID- 1460419 TI - Predominance of fetal type DJH joining in young children with B precursor lymphoblastic leukemia as evidence for an in utero transforming event. AB - The presence of N sequences in the complementarity determining region 3 (CDR3) of the rearranged immunoglobulin H chain is developmentally regulated: N regions are generally present in the DJH joinings of adult B cells but are often absent in fetal B cells. Analysis of the CDR3 in 61 B precursor acute lymphoblastic leukemias indicated that 87.5% of the leukemias obtained from children < or = 3 yr old lacked N regions at the DJH junction. In contrast, in children > 3 yr old, only 11.1% of the leukemias lacked N regions at this junction, a frequency similar to what we have observed in B cells from children and adults. These findings suggest that the majority of leukemias presenting within the first 3 yr of age arise from an in utero transforming event. PMID- 1460420 TI - A severe combined immunodeficient (SCID) mouse model for infection with Entamoeba histolytica. AB - We used severe combined immunodeficient (SCID) mice to study resistance to invasive infection with Entamoeba histolytica. Seven of seven SCID mice developed liver abscesses when challenged intrahepatically with virulent HM1:IMSS strain E. histolytica trophozoites. Only one of seven similarly challenged immunocompetent congenic C.B-17 mice developed an abscess. Adoptive transfer of polyclonal rabbit anti-E. histolytica antiserum, but not preimmune rabbit serum, completely protected 7 of 12 SCID mice from intrahepatic challenge with ameba. These results demonstrate that lymphocyte-based immunity is important in protection against amebic liver abscess, and that anti-E. histolytica antibody can protect against amebic infection in this system. The SCID mouse may provide a powerful model for studying the components of protective immunity to invasive amebiasis. PMID- 1460421 TI - Thymic selection of the human T cell receptor V beta repertoire in SCID-hu mice. AB - Implantation of pieces of human fetal liver and thymus into SCID mice results in the development of a human thymus-like organ, in which sustained lymphopoiesis is reproducibly observed. In this model, T cell development can be experimentally manipulated. To study the influence of thymic selection on the development of the human T cell repertoire, the T cell receptor (TCR) V beta gene repertoire of double-positive (CD4+CD8+) and single-positive (CD4+CD8- and CD4-CD8+) T cells was analyzed in the SCID-hu thymus using a multiprobe ribonuclease protection assay. TCR diversity in double-positive SCID-hu thymocytes was found to be comparable with that present in the thymus of the fetal liver donor, did not change with time, and was independent of the origin of the thymus donor. Thymic selection in SCID-hu thymus induces changes in V beta usage by the single positive CD4+ or CD8+ T cells comparable with those previously reported for single-positive cells present in a normal human thymus. Finally, significant differences were observed in the V beta usage by CD4 or CD8 single-positive T cells that matured from genetically identical stem cells in different thymic environments. Collectively, these data suggest: first, that the generation of TCR diversity at the double-positive stage is determined by the genotype of the stem cells; and second, that polymorphic determinants expressed by thymic epithelium measurably influence the V beta repertoire of mature single-positive T cells. PMID- 1460422 TI - Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance. AB - Antibodies bearing the T15 idiotype dominate the murine primary immune response to phosphocholine (PC). Analysis of antigen binding of antibodies derived from V1:DFL16.1:JH1 (VH1) germline and N region-derived variant heavy (H) chains and kappa 22, kappa 24, and kappa 8 light (L) chains demonstrates that the T15H:kappa 22L (T15) antibody binds PC at least 20-40 times better than other antibodies derived from alternate germline forms of the VH1 H chain and kappa 22, kappa 24, or kappa 8 L chains. To achieve affinities in the same range as the T15 antibody, kappa 24 and kappa 8 L chain-containing antibodies must have H chains derived from variant N region or somatically mutated VH1 genes. Single amino acid differences at the VD junction of the various germline and N region variant VH1 H chains dictate the L chain that can associate with the H chain to produce a PC specific antibody. Several H:L combinations give rise to T15 or M167 idiotype positive antibodies that lack specificity for PC, and single amino acid substitutions or insertions at the VH1:D junction result in the loss of T15 or M167 idiotopes. Based on these observations, our data support a molecular model involving both preferential gene rearrangement and antigen-driven B cell selection to explain T15 idiotype dominance in the immune response to PC. In the absence of N region diversification, large numbers of neonatal B cells bearing the T15H:kappa 22L surface immunoglobulin M (sIgM) receptors would be selected and expanded by autologous or environmental PC antigen into the long-lived peripheral B cell pool. PMID- 1460423 TI - Genetic analysis of MRL-lpr mice: relationship of the Fas apoptosis gene to disease manifestations and renal disease-modifying loci. AB - In MRL mice, the mostly recessive lpr mutation results in both the accumulation of CD4-, CD8-, CD3+ T cells in lymphoid tissue and many features of generalized autoimmune disease, including immune complex glomerulonephritis. To positionally clone the lpr mutation and analyze the effects of background genes, backcross offspring were examined from the cross: (MRL/MpJ-lpr x CAST/Ei)F1 x MRL/MpJ-lpr. The lpr gene was found to be closely linked to a mouse chromosome 19 marker defined by a variation of a Fas gene restriction fragment. Our results identified differences in RNA expression and differences in the genomic organization of the Fas gene between normal and lpr mice, and confirm the recent report that a mutation in the Fas apoptosis gene is the lpr mutation. However, our results also indicate that the Fas gene is expressed in spleen cells from normal mice, and spleen and lymph node cells from mice with a second mutation at the lpr locus (lprcg). Together these results suggest that altered Fas transcription results in the failure of lymphocytes to undergo programmed cell death and may lead to an altered immune cell repertoire. This mechanism may explain certain central and peripheral defects in tolerance that are present in autoimmune disease. The current study also demonstrates the profound effect of background genes on the degree of nephritis, lymphadenopathy, and anti-DNA antibody production. Of major note, our studies suggest the identification of chromosomal positions for genes that modify nephritis. Analysis of the backcross mice for markers covering most of the mouse genome suggests that over 50% of the variance in renal disease is attributable to quantitative trait loci on mouse chromosomes 7 and 12. Moreover, this study provides a model for dissecting the complex genetic interactions that result in manifestations of autoimmune disease. PMID- 1460424 TI - CD45RA and CD45RBhigh expression induced by thymic selection events. AB - CD45 is a protein tyrosine phosphatase involved in T and B cell signaling. While peripheral T cells switch CD45 isoforms upon activation, events leading to exon switching during T cell development in the thymus have not been determined. The expression of high molecular weight isoforms of CD45 was examined on thymocytes from nontransgenic and T cell receptor (TCR) transgenic mice. All thymocytes from nontransgenic mice were CD45RB+ as assessed by staining with MB23G2, an anti CD45RB-specific monoclonal antibody. Interestingly, there was a small population (1-3%) of thymocytes that displayed a higher intensity of staining with MB23G2, CD45RBhigh. CD45RBhigh thymocytes were found in all subsets defined by CD4 and CD8 expression and were also present within the TCR-alpha/beta high population. To analyze whether or not CD45 expression correlated with thymic selection events, expression of CD45RBhigh and a second isoform, CD45RA, was examined on thymocytes from H-Y and 2C TCR transgenic mice and found to correlate with positive and negative selection events but did not occur in nonselecting backgrounds. CD45RA and CD45RBhigh upregulation was also not observed in transgenic mice backcrossed into CD8-deficient mice, a scenario in which there is no positive selection of transgene-expressing thymocytes. These data suggest that modulation of CD45 isoform expression may be involved in thymic selection events. PMID- 1460425 TI - Phagocytic chimeric receptors require both transmembrane and cytoplasmic domains from the mannose receptor. AB - Phagocytosis has traditionally been viewed as a specialized function of myeloid and monocytic cells. The mannose receptor (MR) is an opsonin-independent phagocytic receptor expressed on tissue macrophages. When human MR cDNA is transfected into Cos cells, these usually non-phagocytic cells express cell surface MR and bind and ingest MR ligands such as zymosan, yeast, and Pneumocystis carinii. Expression of cDNA for Fc gamma RI (CD64), the high affinity Fc receptor, in Cos cells confers binding but barely detectable phagocytosis of antibody-opsonized erythrocytes (EA). We report here that chimeric receptors containing the ligand-binding ectodomain of the Fc receptor and the transmembrane and cytoplasmic domains of the MR ingest bound EA very efficiently, whereas chimeras with the Fc receptor ecto- and transmembrane domains and the MR tail, or the Fc receptor ecto- and cytoplasmic domains and the MR transmembrane region, are significantly less phagocytic. All of the chimeric receptors bind ligand with equal avidity, but gain of functional phagocytosis is only conferred by the MR transmembrane and cytoplasmic domains. Endocytosis of monomeric immunoglobulin G by chimeric receptors demonstrates a similar pattern, with optimal uptake by the chimera containing both tail and transmembrane regions from the MR. The chimeric receptors with only the transmembrane or the cytoplasmic domain contributed by the MR were less efficient. Site-directed mutagenesis of the single tyrosine residue in the cytoplasmic tail (which is present in a motif homologous to an endocytosis consensus motif in the LDL receptor cytoplasmic tail [Chen, W.-J., J. L. Goldstein, and M. S. Brown. 1990. J. Biol. Chem. 265:3116]) reduces the efficiency of phagocytosis and endocytosis to a similar extent. PMID- 1460426 TI - Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. AB - Antigen-presenting, major histocompatibility complex (MHC) class II-rich dendritic cells are known to arise from bone marrow. However, marrow lacks mature dendritic cells, and substantial numbers of proliferating less-mature cells have yet to be identified. The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II-negative precursors in marrow. A key step is to remove the majority of nonadherent, newly formed granulocytes by gentle washes during the first 2-4 d of culture. This leaves behind proliferating clusters that are loosely attached to a more firmly adherent "stroma." At days 4-6 the clusters can be dislodged, isolated by 1-g sedimentation, and upon reculture, large numbers of dendritic cells are released. The latter are readily identified on the basis of their distinct cell shape, ultrastructure, and repertoire of antigens, as detected with a panel of monoclonal antibodies. The dendritic cells express high levels of MHC class II products and act as powerful accessory cells for initiating the mixed leukocyte reaction. Neither the clusters nor mature dendritic cells are generated if macrophage colony-stimulating factor rather than granulocyte/macrophage colony stimulating factor (GM-CSF) is applied. Therefore, GM-CSF generates all three lineages of myeloid cells (granulocytes, macrophages, and dendritic cells). Since > 5 x 10(6) dendritic cells develop in 1 wk from precursors within the large hind limb bones of a single animal, marrow progenitors can act as a major source of dendritic cells. This feature should prove useful for future molecular and clinical studies of this otherwise trace cell type. PMID- 1460427 TI - Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: implications for the neuropathogenesis of HIV disease. AB - Human immunodeficiency virus (HIV) infection of brain macrophages and astroglial proliferation are central features of HIV-induced central nervous system (CNS) disorders. These observations suggest that glial cellular interactions participate in disease. In an experimental system to examine this process, we found that cocultures of HIV-infected monocytes and astroglia release high levels of cytokines and arachidonate metabolites leading to neuronotoxicity. HIV-1ADA infected monocytes cocultured with human glia (astrocytoma, neuroglia, and primary human astrocytes) synthesized tumor necrosis factor (TNF-alpha) and interleukin 1 beta (IL-1 beta) as assayed by coupled reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and biological activity. The cytokine induction was selective, cell specific, and associated with induction of arachidonic acid metabolites. TNF-beta, IL-1 alpha, IL-6, interferon alpha (IFN-alpha), and IFN-gamma were not produced. Leukotriene B4, leukotriene D4, lipoxin A4, and platelet-activating factor were detected in large amounts after high-performance liquid chromatography separation and correlated with cytokine activity. Specific inhibitors of the arachidonic cascade markedly diminished the cytokine response suggesting regulatory relationships between these factors. Cocultures of HIV-infected monocytes and neuroblastoma or endothelial cells, or HIV-infected monocyte fluids, sucrose gradient-concentrated viral particles, and paraformaldehyde-fixed or freeze-thawed HIV-infected monocytes placed onto astroglia failed to induce cytokines and neuronotoxins. This demonstrated that viable monocyte-astroglia interactions were required for the cell reactions. The addition of actinomycin D or cycloheximide to the HIV infected monocytes before coculture reduced, > 2.5-fold, the levels of TNF-alpha. These results, taken together, suggest that the neuronotoxicity associated with HIV central nervous system disorders is mediated, in part, through cytokines and arachidonic acid metabolites, produced during cell-to-cell interactions between HIV-infected brain macrophages and astrocytes. PMID- 1460428 TI - Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes. AB - Mice bearing a tumor necrosis factor (TNF) alpha transgene controlled by an insulin promoter developed an increasingly severe lymphocytic insulitis, apparently resulting from the induction of endothelial changes with features similar to those observed in other places of intense lymphocytic traffic. This was accompanied by dissociation of the endocrine tissue (without marked decrease in its total mass), islet fibrosis, and the development of intraislet ductules containing, by places, beta cells in their walls, suggesting a regenerative capacity. Islet disorganization and fibrosis did not result from lymphocytic infiltration, since they were also observed in SCID mice bearing the transgene. Diabetes never developed, even though a number of potentially inducing conditions were used, including the prolonged perfusion of interferon gamma and the permanent expression of a nontolerogenic viral protein on beta cells (obtained by using mice bearing two transgenes). It is concluded that (a) a slow process of TNF release in pancreatic islets induces insulitis, and may be instrumental in the insulitis resulting from local cell-mediated immune reactions, but (b) that insulitis per se is not diabetogenic, lymphocyte stimulation by cells other than beta cells being necessary to trigger extensive beta cell damage. This provides an explanation for the discrepancy between the occurrence of insulitis and that of clinical disease in autoimmune diabetes. PMID- 1460430 TI - Peptide-induced conformational changes in class I heavy chains alter major histocompatibility complex recognition. AB - Small peptides, derived from endogenous proteins bind within the antigen binding groove created by the beta-pleated sheets and alpha helices of the alpha 1 and alpha 2 domains of the class I molecule of the major histocompatibility complex (MHC). However, the precise role of peptide in class I MHC conformation remains unclear. Here, we have shown that, in at least some instances, changes induced in the MHC molecule by the binding of distinct peptides can be identified as specific alterations in serological epitopes expressed on the class I protein. The nature of specific peptides expressed by class I-bearing cells may, therefore, have a dramatic influence on T cell development, self-tolerance, and alloreactivity. PMID- 1460429 TI - Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes. AB - An effective vaccine against the human immunodeficiency virus should be capable of eliciting both an antibody and a cytotoxic T lymphocyte (CTL) response. However, when viral proteins and peptides are formulated with traditional immunological adjuvants and inoculated via a route acceptable for use in humans, they have not been successful at eliciting virus-specific, major histocompatibility complex (MHC) class I-restricted CTL. We have designed a novel viral subunit vaccine by encapsulating a previously defined synthetic peptide CTL epitope of the simian immunodeficiency virus (SIV) gag protein within a proteoliposome capable of attaching to and fusing with plasma membranes. Upon fusing, the encapsulated contents of this proteoliposome can enter the MHC class I processing pathway through the cytoplasm. In this report, we show that after a single intramuscular vaccination, rhesus monkeys develop a CD8+ cell-mediated, MHC class I-restricted CTL response that recognizes the synthetic peptide immunogen. The induced CTL also demonstrate antiviral immunity by recognizing SIV gag protein endogenously processed by target cells infected with SIV/vaccinia recombinant virus. These results demonstrate that virus-specific, MHC class I restricted, CD8+ CTL can be elicited by a safe, nonreplicating viral subunit vaccine in a primate model for acquired immune deficiency syndrome. Moreover, the proteoliposome vaccine formation described can include multiple synthetic peptide epitopes, and, thus, offers a simple means of generating antiviral cell-mediated immunity in a genetically heterogeneous population. PMID- 1460431 TI - Lymphoproliferative disease in human peripheral blood mononuclear cell-injected SCID mice. I. T lymphocyte requirement for B cell tumor generation. AB - Mechanisms of tumor development were studied in SCID mice injected with human lymphoid cells from Epstein-Barr virus-positive (EBV+) donors. About 80% of peripheral blood mononuclear cell (PBMC)-injected animals developed a lymphoproliferative disease associated with oligoclonal EBV+ tumors of human B cell origin. No change in tumor development rate occurred when monocyte-depleted PBMC were inoculated. No tumors developed when purified B cells were injected. B cell lymphoproliferative disease was also prevented in most cases when PBMC injected animals were treated with agents that prevent T cell activation, such as cyclosporin A. Both CD4+ and CD8+ T cell subpopulations were able to provide putative factor(s) necessary for EBV+ B cell expansion and progression to tumors. These data suggest that the transfer alone of potentially tumorigenic human cells into an immunodeficient environment, such as the SCID mouse, might not be sufficient for cell progression to tumor, and raise the possibility that chronic activation events could play a major role in the pathogenesis of some EBV+ lymphomas in the immunocompromised host. PMID- 1460434 TI - A high molecular weight proteoglycan is differentially expressed during development of the mollusc Concholepas concholepas (Mollusca; Gastropoda; Muricidae). AB - Incorporation of radioactive sulfate to hatched veliger larvae of the gastropod muricid Concholepas concholepas indicated that over 87% of the sulfated macromolecules were found in the detergent insoluble fraction, rich in extracellular matrix (ECM) components. The sulfated material was solubilized with guanidine salt followed by urea dialysis and fractionated by DEAE-Sephacel chromatography. Three sulfated compounds eluting at 0.7, 1.1, and 3.0 M NaCl, called peaks I, II, and III, respectively, were obtained. The sulfated compound present in peak I was degraded by pronase or sodium alkaline treatment to a small sulfated resistant material, suggesting the presence of a proteoglycan (PG). Filtration analysis on Sephacryl S-500 and SDS-PAGE of the intact PG indicates that it has a high molecular weight (360,000 to over 1 x 10(6)). Monoclonal antibodies (mAb) against this PG were produced. The specificity of one mAb, the 6H2, was demonstrated by size chromatography and ELISA analysis. The epitope recognized by this mAb seems to be present in the core protein of the PG. Both the extent of sulfation and the presence of different sulfated species of PGs were evaluated during the development of this mollusc. A twelvefold increase in the incorporation of sulfate to PGs per milligram of protein was found in veliger larvae compared to blastula-glastula stages. This change correlated well with the differential expression of the sulfated PG present in peak I. Biochemical and immunological analysis indicate that high levels of this PG are found in veliger and trocophore larvae in comparison with blastula-gastrula and early juveniles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460432 TI - Identification of HLA-DR alpha chain residues critical for binding of the toxic shock syndrome toxin superantigen. AB - Staphylococcal toxic shock syndrome toxin 1 (TSST-1) binds to major histocompatibility complex class II molecules, and the toxin-class II complexes induce proliferation of T cells expressing V beta 2 sequences. To define the residues involved in TSST-1 binding, a set of transfectants expressing 21 HLA-DR alpha chain mutants were analyzed for their abilities to bind and present TSST-1 and to present an antigenic peptide. Mutations at DR alpha positions 36 and 39 markedly decreased the ability of the DR7 molecule to bind and present TSST-1 but did not affect the ability to present an antigenic peptide. These data indicate that DR alpha residues 36 and 39, predicted to be located on an outer loop, are important in the formation of the TSST-1 binding site on DR molecules. PMID- 1460433 TI - Autoaggressive myocytotoxic T lymphocytes expressing an unusual gamma/delta T cell receptor. AB - Polymyositis mediated by gamma/delta T cells is a unique disease in which autoaggressive T lymphocytes surround, invade, and destroy muscle fibers. Histochemically, the vast majority of muscle-infiltrating T cells in a patient with polymyositis were reactive with a pan-gamma/delta T cell receptor (TCR) specific monoclonal antibody (TCR-delta 1+), but unlike > 90% of peripheral blood gamma/delta T cells, these lymphocytes did not react with V delta 1- or V gamma 9 specific antibodies (A13- and Ti gamma A-, respectively). Differential reactivity with two different V delta 2-specific monoclonal antibodies (BB3-/TiV-delta 2+) indicated that the infiltrating T cells express a V delta 2-containing TCR with unusual additional structural features. Using conventional and anchored polymerase chain reaction for the analysis of TCR transcripts, we found a striking predominance of one unusual V delta 2-J delta 3 recombination and one V gamma 3-J gamma 1 recombination. Both the unusual phenotype (TCR-delta 1+/A13-/Ti gamma A-/BB3-/TiV-delta 2+) and the dominance of distinct TCR transcripts are compatible with the assumption that one T cell clone, which expresses a V gamma 3 J gamma 1-C gamma 2/V delta 2-J delta 3-C delta disulfide-linked TCR, dominates among the infiltrating T cells of the polymyositis muscle specimen analyzed. PMID- 1460435 TI - Effect of air exposure on nitrogen metabolism in the crab Cancer pagurus. AB - In C. pagurus exposed to air for 18 h, blood ammonia content decreased within the 2 first hours, then increased at a relatively constant rate (25 microM/h); blood urate content increased at a lower rate (10 microM/h) and a classical blood acidosis was observed. In the cheliped muscle, a transient 22% decrease in GDH activity for ammonia formation and a 48% increase in GDH activity in the reverse reaction (glutamate synthesis) occurred following 6 and 12 h of emersion, respectively. Changes in LDH activity, used as an indicator of anaerobic potential of muscle, were not observed, except for an 18% increase in crabs exposed to air for 24 h. The increase in blood urate content, not known as a response to emersion in decapods, appeared to be different from that observed in response to hypoxia. The relatively low blood ammonia overload and the GDH increased activity for glutamate synthesis suggested that part of the produced ammonia was stored under a bound form in some tissues. The response of C. pagurus to air exposure is discussed on account of the Storey and Storey ('90) theory. PMID- 1460436 TI - The bimodal auditory-vibratory system of the thoracic ventral nerve cord in Locusta migratoria (Acrididae, Locustinae, Oedipodini). AB - In locusts the auditory receptors of the tympanal organs and many of the vibratory receptors of all 6 legs converge at the level of the thoracic ventral nerve cord, forming a combined auditory-vibratory sensory system; it is represented by the VS-, S-, and V-neurons ascending to the supraesophageal ganglion. The connections between vibratory receptors of the different legs and the dendritic inputs of the bimodal ascending neurons are investigated in this report. As an example, the dendritic branches of the G- and V3-neurons for auditory and vibratory input could be localized by simultaneous recording at 2 different positions of the axon. The vibratory input from the receptors of the different legs was determined. Segmental and/or intersegmental thoracic interneurons are intercalated between the receptors and the ascending auditory vibratory neurons (G- and V3-neurons). The morphology and function of 2 intersegmental vibratory interneurons (VI1- and VI2-neurons) are described. They probably connect the vibratory receptors of 1 (or 2) leg(s) of 1 thoracic segment with the different bimodal auditory-vibratory neurons. The importance of the anterior Ring Tract for synaptic connection between receptor cells, first order interneurons, and bimodal auditory-vibratory neurons is discussed on the basis of morphological and physiological data. PMID- 1460437 TI - The role of protein kinase C in reorganization of the cortical cytoskeleton during the transition from oocyte to fertilization-competent egg. AB - Fertilization-competent amphibian eggs (metaphase II) are programmed to undergo an actin-myosin based contraction of the cortical cytoplasm (i.e., cortical contraction) in response to an elevation of intracellular-free calcium which accompanies fertilization. This ability to undergo cortical contraction is acquired within a few hours after the meiotically-arrested oocyte is triggered to resume meiosis by exposure to progesterone. This report examines the timing of changes in the contractile potential of the cortical cytoplasm as the oocyte becomes the egg, and in addition, the signal transduction events which induce these changes. We use the bisected oocyte system developed by Christensen et al. ('84; Nature 310: 150-151) to assess the changes in cortical potential during the meiotic resumption. Immediately after progesterone treatment (less than 5% of the way through the meiotic resumption) the cortex acquires the ability to form a contractile ring, an ability which gradually disappears during the meiotic resumption. Eighty percent of the way through the meiotic resumption the cortex of the hemisphere rapidly acquires the ability to undergo cortical contraction. In contrast, when bisected in a medium containing protein kinase C (PKC) agonists, the cortex of the hemisphere undergoes cortical contraction much earlier (i.e., 50% through the meiotic resumption). In addition, treatment of oocytes with PKC agonists alone can mimic the complete spectrum of changes in cortical potential induced by progesterone, suggesting that PKC has a role in reorganization of the cortical cytoskeleton which occurs as a normal response to progesterone. In support of this, antagonists of PKC block the progesterone induced reorganization of the cortical cytoskeleton. PMID- 1460438 TI - Histochemical heterogeneity of fibers in the abdominal superficial flexor muscles of the Norway lobster, Nephrops norvegicus (L.). AB - The superficial flexor muscle in the abdomen of the Norway lobster Nephrops norvegicus (L.), comprises medial and lateral bundles with distinct fiber type composition. Fibers of the medial bundle have long sarcomeres (> 9 microns) and a thick fringe of subsarcolemmal mitochondria. In histochemical tests they have a low total myofibrillar ATPase activity, a pH-stable isoform of myosin ATPase, and a high level of oxidative enzyme activity. A few fibers of the lateral bundle also display these morphological and histochemical properties. However, the majority of lateral fibers have shorter sarcomeres (< 8 microns), no subsarcolemmal mitochondria, but a well-developed tubular system. They also have a higher total myofibrillar ATPase activity, a pH-labile isoform of myosin ATPase, and a low level of oxidative enzyme activity. The heterogeneous pattern of different fiber types in the lateral bundle of this muscle is similar but not identical in the different abdominal segments and in different individuals. PMID- 1460439 TI - Seasonal changes of the adrenocortical response to stress in birds of the Sonoran Desert. AB - Many avian species of the North American Sonoran desert, e.g., the black-throated sparrow, Amphispiza bilineata, cactus wren, Campylorhynchus brunneicapillus, and curve-billed thrasher, Toxostoma curvirostre, can potentially breed from March/April to August. It is possible that, at least in summer, intense heat and aridity may have inhibitory effects on breeding by precipitating a stress response. Stress typically results in a rise in secretion of adrenocorticosteroid hormones that then inhibit reproduction by suppressing release of gonadal hormones. However, we found that plasma levels of corticosterone were not higher during summer, compared with winter, even in 1989 when summer temperatures were higher than normal. In June 1990, temperatures were also above normal and soared to the highest level recorded in Arizona (50 degrees C). Plasma levels of corticosterone during June were high in black-throated sparrows, but less so in two other species (Abert's towhee, Pipilo aberti, and Inca dove, Scardafella inca) found in more shady riparian and suburban habitat with constant access to water. The adrenocortical response to stress (as measured by the rate of corticosterone increase following capture) was reduced in the hottest summer months in black-throated sparrows, cactus wrens, and curve-billed thrashers, but less so in Abert's towhee an Inca dove. These data suggest that at least some birds breeding in the open desert with restricted access to water are able to suppress the classical adrenocortical response to stress. The response is then reactivated in winter after breeding has ceased. It is possible that this stress modulation may allow breeding to continue despite severe heat. Analysis of plasma from these species indicated that the apparent modulation of the adrenocortical response to stress was not an artifact of reduced affinity or capacity of corticosterone binding proteins. PMID- 1460440 TI - The mechanism of antler casting in the fallow deer. AB - The process by which antlers are detached from their pedicles was examined histologically in fallow deer castrated in the autumn to induce precocious casting. Osteoclastic erosion across an abscission line between the dead bone of the antler and the living bone of the pedicle was found to be responsible for the separation of the 2. As early as 3 days after castration, osteoclasts and associated lacunae were present on the sides of the pedicle bone. These were then found in progressively deeper locations, by 2 weeks extending across the entire width of the pedicle. Concomitant with the centripetal spread of osteoclasts was the enlargement of Haversian canals, the surfaces of which became lined with osteoclasts. These widening vascular channels within the bone were filled with connective tissue, which in precasting stages formed a mesodermal pad about 1 mm thick. In later stages, a circumferential cleft was excavated beneath the antler burr, and connective tissues from the surrounding pedicle skin invaded the space between the antler and pedicle. After casting, the ingrowing integumental tissues fused with the mesodermal tissues derived from the vascular channels of the pedicle to give rise to an incipient antler bud beneath the scab. The ingrowth of epidermis capable of de novo hair follicle formation gave rise to the future velvet skin that envelops the elongating antler. PMID- 1460441 TI - Is the anterior-posterior axis of the fetus specified before implantation in the mouse? AB - The mouse conceptus is generally held to be radially symmetrical about its embryonic-abembryonic axis from the blastocyst stage until the primitive streak appears at the beginning of gastrulation. However, this notion has been challenged by recent observations on conceptuses sectioned in utero which suggest that the blastocyst is already bilaterally symmetrical when it begins to implant. Accordingly, the blastocyst has been assigned an anterior-posterior axis which appears to persist through gastrulation and is claimed to coincide with the anterior-posterior axis of the future fetus in both orientation and polarity. In the present investigation the relationship between these two axes was examined in conceptuses dissected from the uterus early in gastrulation so that it could be determined more accurately than is possible in situ. The anterior-posterior axis of the conceptus and nascent fetus were found to be either parallel or antiparallel to each other, suggesting that while the orientation of the fetal axis may be specified at the blastocyst stage its polarity is not. PMID- 1460442 TI - Cryopreservation of Atlantic croaker spermatozoa: evaluation of morphological changes. AB - The spermatozoon of the Atlantic croaker (Micropogonias undulatus) is a primitive type in that it lacks an acrosome. The kidney-shaped head has a diameter of about 1.5 microns and is occupied by a granular and electron-dense nucleus. The short midpiece contains 3 spherical mitochondria and encircles the basal body of the flagellum but is separated from it. The flagellum consists of the typical 9 + 2 axoneme and surrounding plasma membrane but lacks a lateral ridge. Spermatozoa of Atlantic croaker diluted in either NaCl or sodium citrate solutions with or without DMSO were examined with the electron microscope before freezing in liquid nitrogen and after thawing. Damage following cryopreservation appeared to be greater to the mitochondria, plasma membrane, and 9 + 2 axoneme than to the nucleus. The incidence of postthaw damage in spermatozoa diluted with NaCl solutions containing DMSO was remarkably lower than that with either pure NaCl solutions, pure sodium citrate solutions, or sodium citrate solutions containing DMSO. PMID- 1460443 TI - Fat body ovarian relationship in the garden lizard, Calotes versicolor (Daud.). AB - Abdominal fat body mass of Calotes versicolor showed annual changes that were universal related to the changes in ovarian somatic (GSI) and hepatosomatic (HSI) indices. Fat bodies were absent in late breeding phase (June-August). Thirty day fatectomy (FBX) during prebreeding phase significantly reduced GSI, HSI, and total number of extrastromal follicles; also, recruitment of vitellogenic follicles was arrested and ateretic follicles increased. The FBX during postbreeding phase had no such effect, whereas in 30 day ovariectomised (OvX) lizards in prebreeding phase fat body mass significantly increased but HSI decreased. However, in lizards in prebreeding phase, E2 caused a significant decrease in fat body mass and an increase in HSI, while during the postbreeding phase there was a significant increase in HSI but the fat bodies were not affected. The above findings suggest that the development of the first clutch of vitellogenic follicles in the lizard utilises lipids stored in the fat bodies and that the growth of the subsequent clutches of vitellogenic follicles is met through the intake of food, which is abundant in the latter part of the breeding phase. The fat bodies are not needed for the growth of previtellogenic follicles. The fact that lipolytic action of E2 occurs only during the breeding phase suggests that responsiveness of the fat bodies to the steroid is related to the reproductive phase and that during postbreeding phase of the lizard they become refractory to E2. PMID- 1460444 TI - Arginine vasotocin concentrations in the supraoptic nucleus of the lizard Anolis carolinensis are associated with reproductive state but not oviposition. AB - Arginine vasotocin (AVT) is a neuropeptide involved in reproductive function in many nonmammalian vertebrates. We determined brain and plasma AVT concentrations during the estrous cycle and oviposition in the lizard Anolis carolinensis. There were no differences in AVT concentrations in the plasma or any brain region during the ovipositional sequence. However, we found that females with an egg in each oviduct and a large pre-ovulatory follicle (diameter > 4.5 mm) in one-ovary had significantly higher AVT concentrations in the supraoptic nucleus (SON) of the hypothalamus than did females with small pre-ovulatory follicles in both ovaries. In a second study, females with an egg in each oviduct and a large pre ovulatory follicle had significantly greater AVT concentrations in the SON than females with only one oviductal egg and a large pre-ovulatory follicle or females with an egg in each oviduct and a small pre-ovulatory follicle in each ovary. Concentrations of AVT in other brain regions and in the plasma did not differ among these groups. Changes in steroid profiles during estrous and/or direct neural communication between the uterus, ovary, and brain may account for the changes in AVT concentrations seen in the supraoptic nucleus during the estrous cycle of Anolis carolinensis. PMID- 1460445 TI - Influence of a capacitation period on human sperm acrosome loss. AB - The present study investigates whether a 5 hour capacitation period modifies the ability of human spermatozoa to undergo induced acrosomal loss. Human sperm acrosomal loss was induced by treatment with either the calcium ionophore A23187, low concentrations of the phospholipid dilauroylphosphatidylcholine (PC12), or 2 hours incubation in conditioned medium prepared from human cumulus cells (CM/CC). The use of a dual staining method (FITC-ConA and Hoechst 33258) for simultaneous assessment of acrosomal status and viability demonstrated that induction of acrosomal loss with calcium ionophore was not dependent on a capacitation period. A short (5 hour) incubation period was not sufficient to induce acrosomal loss with CM/CC above spontaneous acrosome reaction rates in medium alone. A significant capacitation-dependent increase (P < 0.05) in acrosomal loss was observed when human spermatozoa were incubated with PC12. Induction of acrosomal loss of capacitated human spermatozoa with PC12 therefore provides a simple assay for the simultaneous assessment of human sperm capacitation and the acrosome reaction in vitro. PMID- 1460446 TI - Indigent care. A possible model for reforming health-care delivery. PMID- 1460447 TI - Health care reform. As efficient as possible. PMID- 1460448 TI - Volunteer health care proposal. PMID- 1460449 TI - Codfish, maybe whales. PMID- 1460450 TI - Preventive health for the elderly. Role of vaccination. AB - Elderly patients should receive three vaccinations as part of routine health maintenance: influenza virus vaccine, pneumococcal vaccine, and tetanus diphtheria toxoid. The injections are inexpensive, well-tolerated, and effective. The greatest barrier to effective immunization of the elderly population is not patient compliance but physician compliance. You are the key to the preventive health of your patients. PMID- 1460451 TI - Single dose oral fluconazole vs intravaginal terconazole in treatment of Candida vaginitis. Comparison and pilot study. AB - Candida vaginitis develops in approximately one-fourth of women in their childbearing years. Conventional management consists of antifungal creams or tablets/suppositories administered intravaginally. Many patients have stated preferences for oral therapy. A randomized, double-blind placebo trial compared the efficacy of a single oral 200 mg dose of fluconazole with the application of terconazole 80 mg vaginal suppository daily for 3 days. Twenty-two patients (fluconazole = 12, terconazole = 10) were evaluated during a four-month period and favorable clinical responses were observed at both early and late evaluations. Mycologic cure was attained by 75% of the fluconazole group and 50% of the terconazole group at the early evaluation. At the late evaluation, mycologic cure was 75% and 100% respectively. The mean time to onset of symptom relief was 2.4 (1.7) days for the fluconazole group and 1.8 (1.8) days for the terconazole group. The mean time to complete relief of symptoms was 6.08 (2.84) and 6.6 (2.95) days respectively. A statistically significant difference did not exist for any of these measures. Seventy-three percent of the patients preferred oral therapy. PMID- 1460452 TI - New onset childhood seizures. Emergency department experience. AB - Fifty-six cases of new onset seizures evaluated in a pediatric emergency department (ED) during a one-year period were assessed retrospectively for efficiency of diagnosis and workup. The majority of patients (69%) were less than two years of age. Based on etiology, the most common seizure type was febrile (71%) followed by idiopathic (21%) and symptomatic (7%). Significant laboratory abnormalities were found in four (7%) patients; two had hyponatremia, one carbamazepine overdose and one bacterial meningitis. Screening laboratory tests including brain CT scans were generally not helpful. A thorough history including specific details regarding the seizure and a complete physical examination should eliminate the need for major laboratory and radiologic workup in the emergency department. PMID- 1460453 TI - Blood-brain barrier and treatment of central nervous system tumors. AB - The blood-brain barrier (BBB) separates the central nervous system (CNS) from systemic blood circulation by a continuous capillary network. The barrier's capillary endothelium has interendothelial tight junctions which prevent passage of large molecular weight, water soluble, highly polar molecules. The barrier protects the brain from toxic substances and also prevents therapeutic drugs from CNS entry. Its permeability within brain tumors is different with fenestrated endothelium resembling that of normal brain regions outside the BBB. Despite capillary changes within CNS tumors, their effect on improved therapies has not been shown. Combined chemotherapy with surgery and radiation does not significantly prolong glioma patients' survival. Discussed are new therapeutic approaches which include: osmotic, transient blood-brain barrier disruption followed by chemotherapy or immunotherapy, drug "tailoring" to render them more effective in barrier entry, and genetic glioma manipulation to make it the target of antiviral drugs which may penetrate the barrier. PMID- 1460454 TI - How to avoid a DPR complaint. AB - Reasons are enumerated why the medical malpractice crisis has abated. Further advice is given on how to avoid a complaint from the Florida Department of Professional Regulation and an explanation is presented of how the DPR functions. An understanding is essential to prevent an investigation and possible disciplinary action by the Board of Medicine. PMID- 1460455 TI - You only get what you do not pay for. PMID- 1460456 TI - Voltage dependence of acetylcholine receptor channel gating in rat myoballs. AB - Whole-cell currents from nicotinic acetylcholine receptor (AChR) channels were studied in rat myoballs using a light-activated agonist to determine the voltage dependence of the macroscopic opening and closing rate constants. Myoballs were bathed in a solution containing a low concentration of the inactive isomer of the photoisomerizable azobenzene derivative, cis-Bis-Q. A light flash was then presented to produce a known concentration jump of agonist, trans-Bis-Q, across a wide range of membrane potentials in symmetrical solutions (NaCl or CsCl on both sides) or asymmetrical solutions (NaCl in the bath and CsCl in the pipette). At the low agonist concentration used in this study, the reciprocal of the macroscopic time constants gives an unambiguous measure of the effective closing rate. It showed an exponential decrease with membrane hyperpolarization between +20 and -100 mV, but tended to level off at more depolarized and at more hyperpolarized membrane potentials. The relative effective opening rate was derived from the steady-state conductance, the single-channel conductance, and the apparent closing rate; it decreased sharply in the depolarizing region and tended to level off and then turn up in the hyperpolarizing region. The two effective rate constants were shown to depend on the first, second, and third power of membrane potential. PMID- 1460457 TI - Shedding of infectious virus and virus antigen during acute infection with respiratory syncytial virus. AB - Shedding of respiratory syncytial virus (RSV) in nasopharyngeal aspirates (NPA) of hospitalized children with acute respiratory infection was studied using direct antigen detection by time-resolved fluoroimmunoassay, rapid identification of infectious virus in centrifugally inoculated cell cultures by immunoperoxidase staining and conventional virus culture. Sequential NPAs, in which also local RSV specific IgA response was measured, were collected from children with proven RSV infection. The shedding pattern was similar for both infectious virus and viral antigen. The overall agreement of the three methods was good (81%) in diagnostic specimens collected on admission, but markedly reduced (46%) in follow-up specimens. Secretory IgA was abundant in specimens giving discrepant or negative results only. The proportion of patients who shed RSV was high (> or = 87%) in the first week after onset of symptoms, and decreased sharply in the second week. An opposite temporal pattern was found in the proportion of patients with detectable RSV-IgA in their secretions. Sequentially isolated strains were antigenically stable as determined by their reactivity with a large panel of monoclonal antibodies. The findings suggest that RSV shedding should be monitored by using more than one method for virus detection. PMID- 1460458 TI - HTLV-I infection in patients with autoimmune thyroiditis (Hashimoto's thyroiditis). AB - To investigate the possible relationship of HTLV-I virus infection to autoimmune thyroid disease, we examined, firstly, the frequency of HTLV-I seropositivity among patients with Hashimoto's thyroiditis and, secondly, the frequency of Hashimoto's thyroiditis in patients with HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Of 144 patients with Hashimoto's thyroiditis in the Tokushima and Kochi Prefectures, Japan, 9 (6.3%) were positive for serum HTLV I virus antibody 2 of whom were confirmed histologically to have Hashimoto's thyroiditis. This percentage is significantly higher (P < 0.01) than the estimated prevalence (2.2%) of HTLV-I carriers among the general population in this region. Of 9 patients with HAM/TSP, 3 (33.3%), including 2 biopsy-proven cases, had evidence of Hashimoto's thyroiditis. This proportion is apparently much higher than the prevalence (1.7%) of Hashimoto's thyroiditis in the general population. These findings suggest that HTLV-I virus may be related to the development of Hashimoto's thyroiditis. PMID- 1460459 TI - Evidence for T-cell involvement during the acute phase of echovirus meningitis. AB - Little is known about the cellular immune response during the acute phase of enterovirus infection. This was studied in patients with echovirus meningitis by analysing changes in the lymphocyte subset distribution both in blood and in cerebrospinal fluid (CSF) and their stage of activation. A significant increase of whole T-cell and CD4+ T-cell counts was observed in CSF in parallel with a slight decrease of T-cell percentage in blood. Activation of the cellular immune response is supported by the observation of elevated neopterin levels in serum and CSF. However, the phenotypic markers of T-cell activation, IL-2 receptor (CD25), and HLA-DR antigens were not detected in blood or in CSF. PMID- 1460460 TI - Current seroepidemiology of hepatitis D virus infection among hepatitis B surface antigen carriers of general and high-risk populations in Taiwan. AB - In order to assess the current seroepidemiology of hepatitis D virus (HDV) infection in Taiwan where hepatitis B virus (HBV) is hyperendemic, a total of 756 voluntary blood donors, 641 prostitutes, 1,014 patients with sexually transmitted diseases (STDs), and 628 drug abusers were studied. Radioimmunoassays were used for testing HBV infection markers and antibody against HDV (anti-HDV) among HBsAg carriers. The anti-HDV prevalence among HBsAg carriers was significantly higher in STD patients (9.6%), prostitutes (33.1%), and drug abusers (68.1%) than in blood donors from the general population (2.2%). The prevalence gradually increased with age in blood donors and STD patients, but reached a plateau at a young age in prostitutes and drug abusers. Males had a higher prevalence than females in blood donors (2.7% vs. 0), STD patients (8.2% vs. 7.5%), and drug abusers (69.0% vs. 57.1%), but the difference was not statistically significant. STD patients with syphilis had a higher prevalence (19.5%) than those affected with non-ulcerating STDs (5.3%). While unlicensed prostitutes had a lower prevalence (13.6%) than licensed prostitutes (44.9%), intravenous drug abusers had a higher prevalence (73.1%) than non-intravenous drug abusers (34.6%). There was a twofold increase in anti-HDV prevalence from 1986 to 1989 among prostitutes, but the prevalence remained unchanged in the general population and drug abusers. HDV infection remains limited to the high-risk groups and spread mainly by promiscuity and needle sharing in Taiwan. PMID- 1460461 TI - Right-side dominance for song control in the zebra finch. AB - Adult male zebra finches underwent unilateral denervation of the syrinx or unilateral lesion of the forebrain nucleus HVC known to be important for song control. Disruptive effects on song were greater after right-side than after left side operations. After denervation of the right half of the syrinx, the fundamental frequencies of all syllables within a song converged on a value near 500 Hz, and nearly all syllables were altered in type. In contrast, the syllables produced after denervation of the left side of the syrinx largely maintained their preoperative frequencies, and fewer syllables changed in type. Unlike nerve sections, HVC lesions did not result in strikingly lateralized effects on syllable phonology; however, HVC lesions did affect the temporal patterning of a bird's song, whereas nerve sections did not, and changes in temporal patterning were more marked after right than after left HVC lesions. Right-side dominance for zebra finch song control is the reverse of that described in other songbird species with lateral asymmetry for vocal communication. We suggest that the need for a dominant side is more important than the side of dominance. PMID- 1460462 TI - Normal and abnormal pathfinding of facial nerve fibers in the chick embryo. AB - Development of the facial nerve was studied in normal chicken embryos and after surgical disruption of ingrowing sensory facial nerve fibers at 38-72 h of incubation. Disruption of facial nerve fibers by otocyst removal often induced a rostral deviation of the facial nerve and ganglion to the level of the trigeminal ganglion. Cell bodies of the geniculate ganglion trailed their deviating neurites and occupied an abnormal rostral position adjacent to the trigeminal ganglion. Deviating facial nerve fibers were labeled with the carbocyanine fluorescent tracer DiI in fixed tissue. Labeled fibers penetrated the cranium adjacent to the trigeminal ganglion, but they did not follow the trigeminal nerve fibers into the brain stem. Rather, after entering the cranium, they projected caudally to their usual site of entrance and proceeded towards their normal targets. This rostral deviation of the facial nerve was observed only after surgery at 48-72 h of incubation, but not in cases with early otocyst removal (38-48 h). A rostral deviation of the facial nerve was seen in cases with partial otocyst removal when the vestibular nerve was absent. The facial nerve followed its normal course when the vestibular nerve persisted. We conclude that disruption of the developing facial pathway altered the routes of navigating axons, but did not prevent pathfinding and innervation of the normal targets. Pathfinding abilities may not be restricted to pioneering axons of the facial nerve; later-developing facial nerve fibers also appeared to have positional information. Our findings are consistent with the hypothesis that navigating axons may respond to multiple guidance cues during development. These cues appear to differ as a function of position of the navigating axon. PMID- 1460463 TI - GAP-43 phosphorylation is dynamically regulated in individual growth cones. AB - In vivo, kinase C phosphorylation of the growth-associated protein GAP-43 is spatially and temporally associated with the proximity of growing axons to their targets. Here we have used dissociated dorsal root ganglia (DRG)s and an antibody specific for the phosphorylated form of GAP-43 to demonstrate that neurite regeneration in culture also begins in the absence of detectable levels of phosphorylated GAP-43. Since the beta isoform of kinase C was found to be enriched in growth cones before stably phosphorylated GAP-43 was detected, it may normally be inactive during initial neurite outgrowth; however, premature phosphorylation of GAP-43 could be stimulated in newly dissociated DRGs by plating them on cultures in which phosphorylation had already been initiated media conditioned by such cultures caused no response suggesting an effect of either cell-cell or cell-substrate contact. Increased GAP-43 phosphorylation correlated with a reduced extent of neurite outgrowth but not with the rate at which individual growth cones translocated so that motile growth cones contained very low levels of phosphorylated GAP-43, whereas stationary growth cones showed much more immunoreactivity. Downregulation of kinase C by phorbol ester prevented increased GAP-43 phosphorylation and led to growth cone collapse. Finally, phosphorylated GAP-43 was found to be differently distributed within growth cones. Increased immunoreactivity was frequently observed in the neck of the growth cone and was heterogeneously distributed in lamellae and filopodia. These results, which demonstrate the dynamic regulation of GAP-43 phosphorylation in individual growth cones, are discussed with reference to the association between changes in growth cone shape and the ability to translocate and change direction. PMID- 1460464 TI - SSB, an antigen that selectively labels morphologically distinct synaptic boutons at the Drosophila larval neuromuscular junction. AB - In this report we describe the expression of Small Synaptic Bouton (SSB), an antigen that is selectively expressed in a specific subset of neuromuscular junction terminals in the body wall of Drosophila larva. The expression of SSB was studied with a polyclonal antibody raised against the cAMP phosphodiesterase of the Drosophila learning mutant dunce (Nighorn et al., 1991, Neuron 6:455-467); however, immunoreactivity was not abolished by the dunce (dnc) alleles dncM14 and dncM11 or deficiencies of the dnc gene, indicating that the antigen labelled could not be the dnc gene product, but another antigen that we termed SSB. Immunoreactivity was localized in the body wall muscles to a specific subset of neuromuscular junction terminals that have been implicated in activity-dependent plasticity. This demonstrates that these morphologically distinct terminals can be immunocytochemically distinguished and that they probably represent innervation by a distinct neuronal population. Confocal and electron microscopic examination demonstrated that staining was restricted to the synaptic boutons themselves, not to neurites or motor axons. Ultrastructural analysis showed label close to synaptic vesicles in the presynaptic terminal and in the surrounding subsynaptic reticulum. Central nervous system (CNS) staining was restricted to a segmentally repeated pattern of cell bodies in the ventral ganglion and to a few small groups of cells in the brain lobes. PMID- 1460465 TI - Cellular interactions determine neuronal phenotypes in rodent retinal cultures. AB - Progenitor cells isolated from early rat embryo retinas differentiate into phenotypes normally generated early in retinal development (e.g., ganglion cells), whereas progenitors isolated from postnatal retinas differentiate into later-generated retinal cell types (e.g., rod photoreceptors; Reh and Kljavin, J. Neurosci. 9:4179-4189; 1989; Adler and Hatlee, 1989; Science 243:391-393; Sparrow, Hicks, and Barnstable, 1990, Dev. Brain Res. 51:69-84). To determine whether this change in committment is intrinsic to the progenitor cells, or alternatively can be modified by interactions with their developing environment, I co-cultured mouse and rat retinal cells, from different developmental stages, and identified the resulting phenotypes with species-specific and cell class specific antibodies. I found that the phenotypes into which mouse neuroepithelial cells differentiate depends on the phenotypes of the rat cells that surround them. Retinal precursor cells from embryonic day (E) 10-12 will adopt the rod photoreceptor phenotype only when close to cells expressing this phenotype. By contrast, when the E10-12 retinal progenitor cells are cultured with cells from the cerebral cortex, they differentiate primarily into large multipolar neurons, similar in their morphology and antigen expression to retinal ganglion cells. These results indicate that interactions among the cells of the developing retina are important in the determination of cell fate. PMID- 1460466 TI - Hypertrophy of gonadotropin releasing hormone-containing neurons after castration in the teleost, Haplochromis burtoni. AB - In the African cichlid fish, Haplochromis burtoni, males are either territorial or nonterritorial. Territorial males suppress reproductive function in the nonterritorial males, and have larger gonads and larger gonadotropin-releasing hormone- (GnRH) containing neurons in the preoptic area (POA). We describe an experiment designed to establish the causal relationship between large GnRH neurons and large testes in these males by determining the feedback effects of gonadal sex steroids on the GnRH neurons. Territorial males were either castrated or sham-operated, 4 weeks after which they were sacrificed. Circulating steroid levels were measured, and the GnRH-containing neurons were visualized by staining sagittal sections of the brains with an antibody to salmon GnRH. The soma areas of antibody-stained neurons were measured with a computer-aided imaging system. Completely castrated males had markedly reduced levels of circulating sex steroids [11-ketotestosterone (11KT) and testosterone (T)], as well as 17 beta estradiol (E2). POA GnRH neurons in castrates showed a significant increase in mean soma size relative to the intact territorial males. Hence, in mature animals, gonadal steroids act as a brake on the growth of GnRH-containing neurons, and gonadal products are not responsible for the large GnRH neurons characteristic of territorial males. PMID- 1460467 TI - Olfactory physiology in the Drosophila antenna and maxillary palp: acj6 distinguishes two classes of odorant pathways. AB - This article provides characterization of the electrical response to odorants in the Drosophila antenna and provides physiological evidence that a second organ, the maxillary palp, also has olfactory function in Drosophila. The acj6 mutation, previously isolated by virtue of defective olfactory behavior, affects olfactory physiology in the maxillary palp as well as in the antenna. Interestingly, abnormal chemosensory jump 6 (acj6) reduces response in the maxillary palp to all odorants tested except benzaldehyde (odor of almond), as if response to benzaldehyde is mediated through a different type of odorant pathway from the other odorants. In other experiments, different parts of the antenna are shown to differ with respect to odorant sensitivity. Evidence is also provided that antennal response to odorants varies with age, and that odorants differ in their age dependence. PMID- 1460468 TI - Depolarization-induced changes in neurite elongation and intracellular Ca2+ in isolated Helisoma neurons. AB - This study focuses on the effects of K+ depolarization on neurite elongation of identified Helisoma neurons isolated into culture. Application of K+ to the external medium caused a dose-dependent suppression of neurite elongation. Lower concentrations of K+ were associated with a slowing in the rate of neurite elongation, whereas higher concentrations produced neurite retraction. Surprisingly, the effects of K+ depolarization were transient, and neurite elongation rates recovered towards control levels within 90 min even though the neurons remained in high-K+ solution. Identified neurons differed in the magnitude of their response to K+ depolarization; neurite elongation of buccal neuron B4 was inhibited at 5 mM K+, but elongation in B5 and B19 was not affected until concentrations of 25 mM. Electrophysiologically, K+ application evoked a brief period (5-10 s) of action potential activity that was followed by a steady state membrane depolarization lasting 2 h or more. The changes in neurite elongation induced by K+ depolarization occurred in isolated growth cones severed from their neurites and were blocked by application of calcium antagonists. Intracellular free Ca2+ levels in growth cones of B4 and B19 increased and then decreased during the 90-min depolarization, corresponding to the changes in elongation. B4 and B19 showed differences in the magnitude, time course, and spatial distribution of the Ca2+ change during depolarization, reflecting their different sensitivities to depolarization. PMID- 1460469 TI - Distribution and developmental change in [3H]MK-801 binding within zebra finch song nuclei. AB - In many songbirds, vocal learning depends upon appropriate auditory experience during a sensitive period that coincides with the formation and reorganization of song-related neural pathways. Because some effects of early sensory experience on neural organization and early learning have been linked to activation of N-methyl D-aspartate (NMDA) receptors, we measured binding to this receptor within the neural system controlling song behavior in zebra finches. Quantitative autoradiography was used to measure binding of the noncompetitive antagonist [3H]MK-801 (dizocilpine) in the brains of both adult and juvenile male zebra finches, focusing on four telencephalic regions implicated in song learning and production. Overall, the pattern of MK-801 binding in zebra finches was similar to the pattern found in rats (Monaghan and Cotman, 1985, J. Neurosci. 5:2909 2919; Sakurai, Cha, Penney, and Young, 1991, Neuroscience 40:533-543). That is, binding was highest in the telencephalon, intermediate in thalamic regions, and virtually absent from the brain stem and cerebellum. The telencephalic song areas exhibited intermediate levels of binding, and binding in the juveniles was not significantly different from adult levels in most song nuclei. However, in the lateral magnocellular nucleus of the anterior neostriatum (IMAN), binding at 30 days of age was significantly higher than binding in adults. Given the established role of NMDA receptors in other developing neural systems, both their presence in song control nuclei and their developmental regulation within a region implicated in song learning suggest that NMDA receptors play a role in mediating effects of auditory experience on the development of song behavior. PMID- 1460470 TI - Measuring health status: what are the necessary measurement properties? AB - The different measurement properties necessary for instruments whose goal is to detect differences between subjects at a single point in time (discriminative instruments) and those whose goal is to detect longitudinal change within subjects (evaluative instruments) is becoming increasingly recognized. Up to now, requirements for evaluative instruments have been presented as reproducibility, validity, and responsiveness (i.e. the ability to detect change over time). An alternative conceptualization would characterize any instrument as requiring two crucial measurement properties. One is validity, the other a high ratio of signal to noise. For discriminative instruments, the signal to noise ratio can be summarized in a reliability coefficient; for evaluative instruments, in a responsiveness index or coefficient. This formulation can simplify and clarify the understanding and teaching of issues in health status measurement. PMID- 1460471 TI - How should health status measures be assessed? Cautionary notes on procrustean frameworks. PMID- 1460472 TI - A methodologic framework for health status measures: clarity or oversimplification? PMID- 1460473 TI - Heart disease in patients with diabetes mellitus. PMID- 1460474 TI - Cost efficient sampling design for quality control of a birth defects registry. AB - Quality control studies of registries are frequently conducted. We employed a cost effective sampling scheme for assessing the quality of case identification and abstracting in one birth defects registry. The general sampling method was a stratified two-stage design, and the optimal sample size for each stratum was chosen to minimize cost, which was defined as time for data collection. The resulting sample sizes depended on the variability in the number of abstracts between and within data collection facilities, and the amount of time needed to complete each data collection step. The most time effective scheme was to visit several facilities each for a short period of time rather than fewer facilities for a longer period of time. Cost efficient sampling strategies, such as the method used here, can be applied to ensure precision in registry quality control analyses and other public health studies. PMID- 1460475 TI - Abdominal pain in a 70-year-old Danish population. An epidemiological study of the prevalence and importance of abdominal pain. AB - In order to assess the prevalence and importance of abdominal pain in the elderly, an epidemiological study of a 70-year-old Danish population was carried out. Seventy two percent of 1119 randomly selected persons answered a questionnaire concerning abdominal pain. One year prevalence of abdominal pain was 28% among women and 17% among men (p < 0.01). Among those with abdominal pain no significant sex difference was found as regards location, severity, frequency, or medicine consumption. Eleven percent of the men and 19% of the women had abdominal pain which they considered to be of importance to their well-being in terms of frequency, severity, or need of medicine (sex difference: chi 2 = 10.18, df = 2, p < 0.01). Participants who had no abdominal pain judged their general health to be better than those who had experienced abdominal pain (p < 0.01). It is concluded that abdominal pain is frequent in a 70 year old population and influences the well-being of the subjects. Further studies are needed to evaluate whether subjects with abdominal pain have a poorer prognosis than subjects without. PMID- 1460476 TI - Different risk factor profiles in young and elderly stroke patients with special reference to cardiac disorders. AB - The risk factors of ischemic cerebrovascular disorders in 77 young patients (< or = 40 years) were compared to those in 138 older patients (> 40 years). The risk factor profile of patients with juvenile stroke was considerably different from that of older patients. Migrainous headache and mitral valve prolapse occurred more frequently in the younger age group, whereas hypertension, diabetes mellitus, high levels of cholesterol and triglycerides were found more often in older patients with stroke. 65% of the women under the age of 40 took oral contraceptives which compares to the baseline community value of 28% of women in childbearing age in this country. Cardiac disorders such as atrial fibrillation, left ventricular hypertrophy, coronary heart disease including a history of myocardial infarction, as well as mitral valve disease were demonstrated more often in the group of elderly patients. 7 out of 77 younger patients (9.1%), and 59 out of 138 older patients (42.8%) were considered to belong to a group with "high cardiac risk for stroke". The results of this study indicate that electrocardiographic screening is of prime importance for detecting cardiac risk factors. However, echocardiographic examination often yields additional diagnostic information, particularly in younger patients. The conflicting opinions concerning the relevance of certain risk factors for ischemic stroke could partly be explained by the fact that these risk factors are distributed unevenly depending on age. PMID- 1460477 TI - Heterogeneity in senile dementia of the Alzheimer type: individual differences, progressive deterioration or clinical sub-types? AB - Although senile dementia of the Alzheimer type (SDAT) is commonly referred to as a disease involving global intellectual deterioration, clinical reports suggest the existence of variable patient profiles. A review of the clinical and biological research reporting heterogeneity in SDAT is summarized in terms of three descriptive models representing stage, compensation and sub-type hypotheses. Together the results suggest the existence of both quantitative and qualitative differences within a SDAT population. While the former may be partly attributable to the use in cross-sectional studies of persons at different stages of the disorder, qualitative differences in clinical evolution, variable patterns in regional cerebral blood flow, genetic markers and type of cognitive deficit strongly suggest the existence of different groups. This hypothesis requires verification by longitudinal neurological and psychometric studies of elderly persons with early dementia. PMID- 1460478 TI - A profile of users of specialty pain clinic services: predictors of use and cost estimates. AB - During the past decade, the multidisciplinary pain clinic has become a popular alternative to the traditional treatment of persistent pain. There is, however, little information describing this population of health care users nor the impact this new demand has on utilization of health care services. The objectives of this study were three fold: to develop a profile of the characteristics of patients referred to a specialty pain clinic including their psychosocial adjustment to their condition; to identify predictors of the use of the specialty services; and to estimate the cost of health service utilization. This historical cohort analytic survey of 571 patients referred to the clinic assessed them for exposure to selected referral variables through a chart review and sampled (n = 222) these patients' current adjustment and health service use through mailed questionnaire. There were four types of use of specialty clinic services. These included: non-users (n = 210); consultation only (n = 180); and the remaining 32% of the referrals were divided between "users-non complete" (n = 98) and "users complete" (n = 83). "User" groups were similar in characteristics to each other at referral and follow-up on all the major variables with the exception of two factors: non-users lived further from the clinic than users and users were rated as psychologically more vulnerable than non-users. The best predictors for attending the clinic were the presence of referral information from the referring physician and the geographic location of the patient's referring physician. The prevalence of poor psychosocial adjustment was 55.7%, high by comparison with other specialty clinics. Seventy percent of the variance in psychosocial adjustment to chronic pain was explained by social and cognitive variables. In addition, users of specialty pain clinic services generated proportionately less costs in the use of other health services when they were compared to non-users. The importance of social support and meaning of illness variables in predicting psychosocial adjustment to chronic pain is corroborated in this study as is the relevance of the pain clinic cognitive behavioural approach for these problems. In addition, compared to other chronic pain sufferers with similar characteristics, it appears that the use of the pain clinic contains the use of other services and thus has an important economic impact. PMID- 1460479 TI - Determinants of sex hormone levels in men as useful indices in hormone-related disorders. AB - Because the determinants of serum sex hormone levels in men have been infrequently studied, we investigated the relation of several personal characteristics to serum levels of testosterone (T), dihydrotestosterone (DHT), estrone (E1), estradiol (E2) and sex hormone-binding globulin (SHBG) among 98 Japanese American men in Hawaii, aged 52-74. The SHBG levels and T/(E1 + E2) ratios decreased progressively with increasing body mass index. The SHBG levels were also inversely associated with hematocrit levels. Serum androgen and estrogen levels did not correlate with smoking, alcohol intake, serum cholesterol, serum uric acid and blood pressure. Some of the associations observed in the present study may be implicated in the etiology of hormone related neoplasms in men. PMID- 1460480 TI - The association of antihypertensive treatment patterns and adverse lipid effects in population-based studies. AB - We investigated the relationship between antihypertensive drug treatment of hypertensives and their mean serum lipid concentrations in population based studies in Germany. Data from three surveys (Luebeck Blood Pressure Study (LBS) of 1984, MONICA Augsburg Survey I of 1984/85, MONICA Augsburg Survey II of 1989/90), obtained on random samples of the population aged 25-64 years, were used for cross-sectional analyses. Moreover, prospective analyses were carried out on participants of the MONICA Augsburg cohort study of 1987/88 (3-year-follow up of the MONICA Survey I). Blood pressure, non-fasting serum total cholesterol and HDL-cholesterol, and body height and weight were measured under strictly standardized conditions. Interview data were available on medical history including medication use, and on smoking and alcohol consumption. In cross sectional and prospective analyses treated male and female hypertensives in each population had significantly lower crude mean HDL-C concentrations than untreated hypertensives, borderliners, or normotensives. Differences in mean HDL-C between untreated and treated hypertensives were attenuated but still significant after control of confounders and ranged from 1.8 to 6.1 mg/dl (i.e. in relative terms, 3.4 to -12.9%) in men and from 3.6 to 9.4 mg/dl (-5.7 to -14.9%) in women. By contrast, crude and multivariate associations of antihypertensive treatment with non-HDL-C (total minus HDL-C) levels were inconsistent and not significant. The inverse association of drug therapy with HDL-C was confirmed by prospective analyses in the MONICA cohort study supporting a causal relationship. Treatment patterns in a community (prevalence of prescribed drug classes) correlated with the magnitude and significance of HDL-C effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460481 TI - Palliative care in non-cancer patients and the neglected caregiver. AB - Diseases other than cancer can be progressive and have a terminal phase and many of the philosophies of palliative care are applicable. The case studies emphasize two types of palliation. First, for the patient and that is well recognized and second, palliation for the caregiver which should include provision of respite care. PMID- 1460482 TI - Estimating the benefits of cholesterol lowering: are risk factors for coronary heart disease multiplicative? PMID- 1460483 TI - Problems with kappa. PMID- 1460484 TI - Modulation of BUdR labeling index in rat brain tumors following intracarotid ACNU administration. AB - Chloroethylnitrosourea (CENU) chemotherapy has yielded limited benefit on survival of malignant brain tumors. Intracarotid administration of CENU is expected to have the advantage of increasing drug concentration reaching tumors. To understand basic knowledge of intracarotid chemotherapy, we monitor changes of proliferating rate after intracarotid injection of 1-(4-amino-2-methyl-5 pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), using a bromodeoxyuridine (BUdR) labeling index (LI) in transplanted brain tumors of three cell strains. C6-2 tumor cells were in vitro sensitive to ACNU, and C6 2/ACNU and C6-1 cells were resistant. The drug sensitivity to ACNU was as follows: 11.9 microM in the C6-2 cells, 46.0 microM in the C6-2/ACNU cells, and 49.7 microM in the C6-1 cells at SD10, which gives 10% survival of clonogenic cells. The intracarotid ACNU at a dose of 30 mg/kg abruptly decreased the LI to 11% (mean) from 36% in C6-2 transplanted tumors. The LI remained low between 12 and 48 hours after, and then increased to the pretreatment level by 96 hours. In contrast, the LI of C6-1 tumors transiently fell to 15% from 42% at 12 hours after the injection, and subsequently increased to 36% at 24 hours and 37% at 48 hours. These results indicate that intracarotid ACNU administration shortly suppresses proliferating activity of tumors and that combined and alternating chemotherapy are mandatory for enhancing effectiveness of brain tumor chemotherapy. PMID- 1460485 TI - MR imaging of experimental meningeal melanomatosis in nude rats. AB - MR imaging of the rat brain has become an increasingly frequently used method in experimental neuroradiology. On a generally available 1.5 T whole body tomograph, supplemented with an individually made small coil and a special SE sequence we obtained fairly fine images of the structures of the rat brain. With gadolinium DTPA, we were able to visualize posterior fossa and cervical leptomeningeal growth of intrathecally injected B16 melanoma in nude rats. Using MRI to follow experimental leptomeningeal metastasis, may provide a new means for diagnostic evaluation and preclinical testing of treatment modalities. PMID- 1460486 TI - Differentiation of a primitive neuroectodermal tumor into a benign ganglioglioma. AB - We describe a case of cerebellar neuroblastoma with histologic documentation of maturation into a ganglioglioma sixteen months later. Only chemotherapy was administered following the initial surgery and the child is well and disease-free three years following her final surgical procedure. The outcome of this patient supports previous hypotheses that the cerebellar neuroblastoma may be a less malignant tumor than its other primitive neuroectodermal posterior fossa counterparts. Furthermore, this case suggests a role for second-look surgery in the management of selected pediatric brain tumors. PMID- 1460487 TI - Quality of life self-reports from 200 brain tumor patients: comparisons with Karnofsky performance scores. AB - To test a method of assessing quality of life, 200 primary brain tumor patients in an outpatient clinic answered a 20-minute questionnaire covering ten aspects of quality of life. These results were compared with Karnofsky performance scale (KPS) scores, taking age into account. Among patients with KPS 90-100 (two-thirds of the patients), the KPS alone was difficult to interpret. The questionnaire, with its specific questions related to the key dimension of well-being, provided a more definitive assessment of status. The central importance of well-being was supported by its strong statistical relationships with other dimensions. Particularly, well-being was related to freedom from depression (p < 0.0001), active social life (p < 0.0001), energy (p < 0.01), and fewer symptoms (p < 0.05). The KPS was more useful in differentiating the other one-third of the patients (KPS 50-80) but was highly sensitive to age. KPS scores, therefore, may have been unreliable. Depression, reported by half of the patients, was not predicted by the KPS when age was excluded from the regression analysis but was related to the scores in well-being and socializing. Neither depression, well being, nor socializing was influenced by age. Thus, the questionnaire directly assessed these central, emotionally based variables, particularly among patients with satisfactory KPS. Such an assessment is especially crucial as a supplement to the KPS in evaluating brain tumor survivors, whose emotional well-being is often severely challenged by treatment after surgical excision. PMID- 1460488 TI - Multiple-fraction-per-day external beam radiotherapy for adults with supratentorial malignant gliomas. AB - The prognosis following therapy for adults with supratentorial malignant gliomas is poor. Standard therapy of 60 Gy of external beam radiotherapy with chemotherapy achieves a median survival time of 35 to 51 weeks following surgery. A variety of innovative therapies have been considered for therapy of malignant gliomas. Multiple-fraction-per-day (MFD) external beam radiotherapy has been evaluated by many investigators. The rationale for MFD teletherapy is based upon exploiting differences in the recovery capacity for radiation damage between slowly and rapidly proliferating tissues and/or shortening the overall treatment time. A large number of clinical trials have, for the most part, failed to show any survival benefit from MFD radiotherapy. These trials have utilized b.i.d. and t.i.d. radiotherapy with fraction sizes of 0.89 to 2 Gy to total doses of 30-81.6 Gy. The linear quadratic model of the radiation cell survival curve suggests that a biological effective tumoricidal dose > or = 10% higher than standard daily radiotherapy, with approximately isoeffective normal tissue damage, could be achieved at 1.2 Gy b.i.d. to a total dose of approximately 72 Gy. Trials of low dose per fraction MFD radiotherapy, to total doses less than 72 Gy, would be predicted to be inadequate to the task. PMID- 1460489 TI - The prognostic significance of postoperative residual contrast enhancement on CT scan in pediatric patients with medulloblastoma. AB - The clinical and therapeutic features of 20 patients with medulloblastoma treated at Children's Hospital and Medical Center, Seattle, from 1980 to 1987, were retrospectively analyzed with regard to prognosis. The overall actuarial 5-year survival rate was 63%, with 57% of patients free from recurrence at 5 years. Residual contrast enhancement on CT scans taken immediately postoperatively was associated with a significantly decreased 5-year recurrence-free survival rate; the 5-year recurrence-free survival rate was 100% for those patients without post operative residual enhancement compared to 41% for those patients with residual enhancement. A high risk group of patients with residual contrast enhancement persisting one year following diagnosis was identified. No patient in this group survived without disease progression. Other factors, including sex, age at diagnosis, evidence of tumor dissemination, or extent of surgical resection as reported by the neurosurgeon, did not significantly influence prognosis. PMID- 1460490 TI - Primary central nervous system lymphoma: a role for adjuvant chemotherapy. AB - Sixteen immunocompetent patients, 10 of whom were previously reported, with primary non-Hodgkins lymphoma of the central nervous system (PCNSL) were treated and followed longitudinally by the Neuro-oncology Service at the University of California, San Francisco (UCSF) and the University of California, San Diego (UCSD). After undergoing surgery (biopsy or resection), these patients received radiation therapy (RT) with hydroxyurea (HU) followed by adjuvant chemotherapy with the combination of procarbazine, CCNU, and vincristine (PCV) as previously reported. All patients ultimately died of progressive recurrent PCNSL. Toxicity using the HU + RT followed by PCV schedule was tolerable. Median and quartile survival data (41 and 65 months, respectively) suggest efficacy for this chemotherapy schedule and further emphasizes a role for adjuvant chemotherapy in the primary treatment of PCNSL. PMID- 1460491 TI - Meningeal hemangiopericytoma: defining the role for radiation therapy. AB - Meningeal hemangiopericytoma is a rare neoplasm arising from perivascular pericytes. Accounting for < 1% of all brain tumors, these neoplasms are characterized by a high local recurrence rate and metastatic potential. Meningeal hemangiopericytoma occur most frequently during the fifth decade of life, with an almost equal sex incidence. To evaluate and define the role for primary, postoperative, or palliative radiotherapy in meningeal hemangiopericytoma, data were gathered from our own tumor registry and compiled with an extensive analysis of published series and case reports. This analysis reveals a 90%, 9 year actuarial risk for local recurrence following surgical resection only. Interestingly, less than 33% of these recurrences were noted within the first five years, which may account for the false assumption that these tumors are highly curable with surgical resection only. Radiation therapy appears to reduce this local recurrence rate, prolonging disease-free and overall survival. Radiation responses are dose dependent, with > 50 Gray providing superior long term disease-free survival. Meningeal hemangiopericytoma are characterized by a slow, but progressive radiographic response to ionizing radiation, not unlike other radiated, highly vascular brain lesions, such as arteriovenous malformations. A retrospective review of clinical demographics, sites of meningeal origin, radiographic and pathologic findings and the role of chemotherapy is also presented. PMID- 1460492 TI - Going critical: 50 years of nuclear energy. PMID- 1460493 TI - Quantification of walking exercise required for improvement of dipyridamole thallium-201 image quality. AB - Dipyridamole 201Tl imaging is an accepted diagnostic procedure for the evaluation of patients unable to perform adequate treadmill exercise, but is limited by high infradiaphragmatic activity. While recent studies have shown that the addition of exercise reduces this activity, the amount of exercise needed to effect such an improvement is uncertain. To prospectively evaluate the amount of walking exercise required to produce improvement in image quality, 120 patients were randomized to either a control group receiving dipyridamole alone, or to dipyridamole supplemented with one of four exercise protocols. Ratios of heart-to liver and heart-to-adjacent infradiaphragmatic activity were generated from anterior images acquired immediately following the test. Heart-to-total infradiaphragmatic activity was also graded semiquantitatively. Results showed improved target-to-background ratios as well as semiquantitative assessment of image quality for dipyridamole supplemented with exercise as compared to dipyridamole alone. No difference was seen between walking in place and Bruce treadmill exercise at Stage 0 or 0.5. A trend towards higher values was seen with Bruce Stage 1 exercise supplementation, but this did not reach statistical significance. No significant complications occurred during the study. We conclude that 3 min of walking exercise is a safe and effective means of improving the quality of dipyridamole 201Tl images. PMID- 1460494 TI - Determination of extent and location of coronary artery disease in patients without prior myocardial infarction by thallium-201 tomography with pharmacologic stress. AB - Seventy-six patients undergoing pharmacologic stress 201TI tomography and coronary angiography within 14 +/- 12 days were studied to determine how well coronary artery disease extent and location could be determined by this scintigraphic technique. No patient had prior myocardial infarction or revascularization. Scintigrams were scored visually and quantitatively. Angiographic lesions > or = 50% were considered significant. Receiver operating characteristic curves were generated for the scintigrams against the angiographic gold standard. Predictive accuracies were determined and compared with the quantitative results. Predictive accuracy was 0.49 for visual and 0.58 for computer identification of single-vessel disease, 0.52 for both visual and computer identification of multivessel disease, 0.64 for both in correctly localizing left anterior descending artery disease, 0.78 versus 0.70 for the right coronary artery and 0.72 versus 0.68 for the left circumflex artery. For the overall detection of disease, the predictive accuracies were 0.79 and 0.80. Although high diagnostic accuracy for detection of coronary artery disease by this approach has been previously documented, the assessment of extent of disease in patients without prior myocardial infarction appears limited. PMID- 1460495 TI - Referral bias and the efficacy of radionuclide stress tests: problems and solutions. PMID- 1460496 TI - Serial tomographic imaging with technetium-99m-sestamibi for the assessment of infarct-related arterial patency following reperfusion therapy. AB - The purpose of this study was to determine the relationship of changes in the severity and extent of hypoperfusion on serial tomographic 99mTc-sestamibi images with patency of the infarct related artery during acute myocardial infarction. We studied 109 patients with acute myocardial infarction using tomographic 99mTc sestamibi imaging acutely and at 18-48 hr later. Perfusion defect extent and defect area, an index of defect severity, were measured on both studies. Both defect extent and defect area were significantly (p = 0.0001) greater for anterior infarctions than for inferior and lateral infarctions. By two factor analysis of variance, the change in defect area varied significantly with both infarct location (p = 0.0001) and patency of the infarct-related artery (p = 0.002). The change in defect extent also varied significantly with both infarct location (p = 0.0001) and with patency of the infarct-related artery (p = 0.004). In patients with inferior myocardial infarction, a change in defect extent or defect area of greater than 4% or 0.017, respectively, had a positive predictive accuracy of 96% and 93%, respectively, for the identification of a patent infarct artery. Therefore, sequential changes on tomographic 99mTc-sestamibi images are of potential value for the noninvasive assessment of patency of the infarct related artery. PMID- 1460497 TI - Early thallium imaging after percutaneous transluminal coronary angioplasty: tomographic evaluation during adenosine-induced coronary hyperemia. AB - This study examined the immediate results of 201Tl imaging during adenosine induced coronary hyperemia in 25 patients with one-vessel coronary artery disease, 4 +/- 3 days after percutaneous transluminal coronary angioplasty (PTCA). There were special features in our study: use of quantitative angiography and single-photon emission computed tomography (SPECT); a homogeneous group of patients (one-vessel disease) and a uniform stress (adenosine infusion). As a group, quantitative coronary angiography showed a decrease in percent diameter stenosis from 72% +/- 12% to 23% +/- 14%, p < 0.001. The thallium images were normal in 17 patients and abnormal in eight patients. However, of the eight patients, four had residual stenosis either in a secondary branch or downstream; one patient had local dissection (the residual stenosis could not be assessed reliably), two patients had > 50% residual diameter stenosis, and one patient had previous Q-wave myocardial infarction with a corresponding fixed thallium defect. In each of the eight patients with an abnormal image, a logical explanation could be identified. Thus, our results suggest that maximum reactive coronary hyperemia returns to normal immediately after PTCA, and that abnormal thallium results are due to inadequate dilatation or associated lesions. PMID- 1460498 TI - Volume expanded diuretic renography in the postnatal assessment of suspected uretero-pelvic junction obstruction. AB - Controversy surrounds the role of 99mTc-diethylenetriamine pentaacetic acid renography in suspected uretero-pelvic junction obstruction in early life. Accordingly, we retrospectively reviewed 18 patients (28 hydronephrotic kidneys) with a mean age of 2 mo (range: 1 wk-6 mo) who underwent a total of 36 scans using intravenous volume expansion (10 ml/kg) and furosemide diuresis (1 mg/kg). Initial scans were classified as obstructed, not obstructed or indeterminate using differential renal function, furosemide washout T 1/2 and visual assessment of tracer clearance. Those initially classified as obstructed (n = 8) have been surgically confirmed. In the indeterminate (n = 6) and nonobstructed (n = 14) groups, three and two kidneys, respectively, developed obstruction on progress scans. Mean follow-up in the nonsurgical patients was approximately 9 mo (range: 4-17 mo). A total of 13 kidneys had developed obstruction by renographic criteria, and to date 12 have surgical confirmation. Our data indicate that: (1) scans classified as obstructed correlate well with surgery; (2) an initial classification of indeterminate or nonobstructed does not exclude later development of obstruction; and (3) serial scans correctly stratify children with possible uretero-pelvic junction obstruction. PMID- 1460499 TI - Tracking the natural history of infantile hydronephrosis with diuretic renography. PMID- 1460500 TI - Cerebral glucose metabolic rates after 30 and 45 minute acquisitions: a comparative study. AB - This study was undertaken to determine if measurements of absolute regional cerebral metabolic rate for glucose (rCMRglc) and variance of rCMRglc are independent of time between 30 and 45 min following injection of the radiotracer. Sixteen subjects received two sets of 18FDG PET scans commencing 30 and 45 min following intravenous injection of 18FDG. No statistically significant differences were detected in either absolute rCMRglc or rCMRglc variance between the two sets of scans. These data demonstrate that for most FDG PET studies, scanning can commence 30 min after injection of the radiotracer without compromising the metabolic data. PMID- 1460501 TI - Iodine-131 contamination from thyroid cancer patients. AB - High-dose radioactive iodine therapy using 131I is the treatment of choice for patients with thyroid cancer following thyroidectomy. Because of the large amount of activity which is excreted during hospitalization, contamination hazard from 131I excretion via perspiration, saliva, breath and urine may arise. In eight patients treated with doses of 131I ranging from 3.7 to 14.8 GBq (100-400 mCi), activity levels were measured in room air, from room surfaces, the toilet, the patients' exhaled breath, skin, saliva and toothbrushes, and the gloves used by medical staff. Thyroid bioassays were also performed on medical staff personnel caring for these patients both before and two days after administration of the treatment dose. Removable activity from the skin was positively correlated with treatment dose and reached a maximum at 24 hr post-therapy. Removable activity from room surfaces exceeded the level of contamination which requires clean-up in a restricted area during the patient's hospitalization. Thyroid bioassays on medical staff showed no significant uptake 2 days after treatment. The relatively high activities present in the saliva, urine and on the skin of these patients emphasizes the need for all individuals coming in contact with these patients to be made aware of the contamination hazard present. PMID- 1460502 TI - How harmful to others are iodine-131 treated patients. PMID- 1460503 TI - Detection of extrapulmonary tuberculosis with gallium-67 scan and computed tomography. AB - We evaluated 23 patients with extrapulmonary tuberculosis (TB) with 67Ga imaging to assess its usefulness in the diagnosis of this condition. We performed computed tomography (CT) in 17 patients to assess CT features of extrapulmonary TB in comparison with findings from 67Ga scans. Nineteen of 23 patients (83%) had positive findings on 67Ga scans. One of five patients with tuberculous mediastinal lymphadenopathy, two patients with cervical lymphadenitis and a patient with renal TB had negative 67Ga scans. It was observed that the detection of previously unrecognized primary foci of TB, without concomitant pulmonary TB, was possible using 67Ga imaging in five patients (22%). The 67Ga scan was relatively sensitive for the localization of extrapulmonary TB. It is suggested that the 67Ga scan could serve as a screening method, when followed by CT and ultrasonography, for the initial detection of occult tuberculous lesions, especially in patients with prolonged fever. PMID- 1460504 TI - Left ventricular volume calculation using a count-based ratio method applied to first-pass radionuclide angiography. AB - Most count-based radionuclide methods for calculating left ventricular volume rely on measurement of radioactivity in a peripheral blood sample and a measurement of ventricle to collimator distance. We have developed a method which requires neither a blood sample nor a distance measurement and which is applicable to first-pass radionuclide angiography. The parameters used to calculate volume are the area of pixel, the total counts in the left ventricle and the maximum pixel count. The equation was used to calculate the volumes in 50 patients who had both resting first-pass radionuclide angiography (25 patients with a single crystal and 25 patients with a multicrystal camera) and contrast ventriculography on the same day. Correlation coefficients for end-diastolic and end-systolic volumes showed r ranging 0.93-0.98 and standard error of estimate ranging 23-35 ml for end-diastolic volume (14%-17% of mean end-diastolic volume) and 16-23 ml for end-systolic volume (18%-21% of mean end-systolic volume). Image processing software for extracting the needed values is generally available on most commercial nuclear medicine imaging systems and the additional time for the calculations is short. Although the theory is based on multiple assumptions, the volume calculation appears to be reasonably accurate and clinically applicable. PMID- 1460505 TI - Noninvasive assessment of regional cardiac adenosine using positron emission tomography. AB - One of the early metabolic changes associated with myocardial ischemia is the breakdown of adenine nucleotides resulting in the enhanced production of adenosine. In order to image regional cardiac adenosine by positron emission tomography (PET) the enzymatic conversion of adenosine into [11C]-S adenosylhomocysteine ([11C]SAH) was used in the presence of 11C-labeled homocysteine thiolactone (adenosine + [11C] - homocysteine-->[11C] - SAH + H2O). Following production of an experimental coronary constriction in anesthetized dogs carrier added 1-[11C]-D,L-homocysteine thiolactone (5-27 mCi, 30 mg/kg) was infused over 1 min. This intervention, while hemodynamically ineffective, increased the plasma homocysteine concentration from 2.5 to 306 microM, which thereafter declined with a T1/2 of 28 min to 97 microM after 60 min. During the first minutes following infusion of [11C] homocysteine, the radioactivity concentration in the blood pool, the nonischemic and the ischemic myocardium were similar. Between 20 and 60 min, however, the regional radioactivity concentration was highest in the perfusion area of the stenosed vessel: 6.6% compared to 5.2 and 5.2% of the injected dose per 1 I tissue. The elevated radioactivity concentration was strictly confined to the perfusion area of the occluded artery. Using [35S]-L-homocysteine (20 microCi; 30 mg/kg) chromatographic separation of SAH in tissue extracts confirmed that the radioactivity accumulation was due to trapping of adenosine in the cellular SAH-pool. These experiments provide first evidence that 1-[11C]homocysteine thiolactone can be successfully used to assess regional adenosine formation in the heart with PET via measurement of [11C] SAH accumulation. PMID- 1460506 TI - PET imaging of carbon-11-S-adenosylhomocysteine: a measure of myocardial energy balance? PMID- 1460507 TI - Chromatofocusing studies involving a monoclonal Fab'. AB - Isoelectric focusing (IEF) of the Fab' derivative of murine monoclonal antibody ZCE-025 is known to detect at least six bands having isoelectric points (pI) ranging from 5.4 to 7.8. Chromatofocusing was employed to separate these bands. Electrophoresis of the starting materials under nonreducing conditions indicated all of the materials to migrate as Fab'. The electrophoresis of urine samples obtained from Balb/c and nude mice 8 hr after the i.v. injection of the various 125I bands revealed the low pI bands to migrate approximately as a 125I-Fab'. The higher pI band activity was located in lower molecular weight regions. Serum samples taken at 8 hr postinjection from the above mice revealed a series of what appeared to be high molecular weight complexes and some low molecular weight species. Biodistribution studies in comparison Balb/c mice and nude mice revealed that the low pI 125I-Fab' bands gave an organ and tumor uptake at 8 hr very similar to Fab', while the high pI 125I-Fab' bands were rapidly excreted into the urine and feces and did not concentrate in the tumor. The data suggest that the population of molecules making up the Fab' of this antibody is heterogeneous and variably stable. Theoretically, some of the entities observed could be counter productive to successful radioimmunoimaging. It is also possible that some of the labeled molecules are associating in vivo with endogenous proteins that might, in some Mabs, affect the biodistribution of the radiopharmaceutical. PMID- 1460508 TI - c-erbB2 protein overexpression in breast cancer as a target for PET using iodine 124-labeled monoclonal antibodies. AB - ICR 12, one of a panel of rat monoclonal antibodies recognizing the external domain of the human c-erb B2 proto-oncogene product, (Styles, 1990) was chosen as a candidate for radiolabeling with 124I for positron emission tomography of selected patients with breast cancer. By using N-bromosuccinimide (NBS), optimal labeling conditions were established using 125I. The labeling efficiency was determined using instant thin-layer chromatography (ITLC) and gel filtration (HPLC). The antibody was then labeled with the positron emitter 124I, and a labeling efficiency of 96% and immunoreactivity of 80%-90% was obtained. The product was stable, with less than 5% of the radiolabel being eluted after six days storage in plasma at 37 degrees C. Immunolocalization studies were performed in athymic mice bearing human breast carcinoma xenografts overexpressing the c erb B2 gene product using as controls 125I labeled isotype-matched rat antibody, and antigen-negative tumors. Good uptake of 124I-labeled ICR12 was obtained in c erb B2 expressing tumors (up to 12% injected dose per gram at intervals up to 120 hr), with localization indices of 3.4-6.2. Tumor xenografts of 6 mm diameter were successfully imaged with high resolution at 24, 48 and 120 hr using the RMH/ICR MUP-PET camera. We suggest that 124I-labeled ICR12 is a suitable agent to image and quantify immunolocalization in patients whose tumors overexpress the c-erb B2 proto-oncogene product. PMID- 1460509 TI - Radiolabeled antibodies to oncogene-encoded molecules for tumor imaging and therapy. PMID- 1460510 TI - Significance of secondary ion mass spectrometry microscopy for technetium-99m mapping in leukocytes. AB - Secondary ion mass spectrometry (SIMS) microscopy is the only method potentially capable of mapping all the elements in the periodic table including stable and radioactive isotopes. We used this method to study 99mTc distribution by detecting and localizing of 99Tc, a daughter product which has the same mass and the same chemical properties. It was combined with albumin macroaggregates or with Hexamethylpropylene-amine oxime (HMPAO) in leukocytes. The efficiency of 99Tc ionization under Cs+ bombardment was higher than with an O2+ beam. By using high mass resolution we succeeded in detecting and localizing 99Tc in cell sections by eliminating polyatomic ions that arise from this biological matrix. The 99Tc specific signal was obtained with a mass resolution of 2000 for labeled albumin macroaggregates, and 5000 for HMPAO-labeled leukocytes. In the latter, the labeling varied from one cell to another and 99Tc was present in both the nucleus and the cytoplasm. The results indicate that SIMS microscopy can provide new insights into 99mTc dosimetry. PMID- 1460511 TI - Plasmapheresis in radioimmunotherapy of micrometastases: a mathematical modeling and dosimetrical analysis. AB - The feasibility of combining plasmapheresis with a large administration of radiolabeled antibody in order to overcome the "binding-site" barrier to antibody penetration in targeting hematologically distributed micrometastases is examined. In such a strategy, intravenous administration of excess radiolabeled antibody, to saturate antigen sites on the cell cluster periphery, is followed by removal of unbound antibody from the plasma, by plasmapheresis, to reduce the absorbed dose to the red marrow. Plasma antibody kinetics are simulated by a non-linear compartmental model representing free and antigen-bound antibody. This provides the boundary condition for a model of antibody diffusion, saturable binding to and dissociation from antigen sites within a 200 microns diameter cluster of tumor cells. Using these models, the absorbed dose to the red marrow and the absorbed dose profile across the cell cluster are calculated. Changes in marrow and cell cluster absorbed dose from alterations in the onset time and rate of plasmapheresis are illustrated for antibody labeled with 123I, 125I and 131I. The results demonstrate that the "binding site" barrier may be overcome, yielding a 2 to 100-fold improvement in the cell cluster absorbed dose for a given bone marrow absorbed dose. PMID- 1460512 TI - Radioimmunotherapy of micrometastases: a continuing evolution. PMID- 1460513 TI - Development of a monoclonal antibody specific for beta/A4 amyloid in Alzheimer's disease brain for application to in vivo imaging of amyloid angiopathy. AB - We evaluated the efficacy of murine monoclonal antibodies (Mabs) targeted to beta/A4 amyloid for development of procedures for the in vivo identification of amyloid angiopathy (AA) in Alzheimer's disease (AD). Mabs to beta/A4 amyloid were prepared and screened for effectiveness in visualizing AA and senile plaques in postmortem AD brain sections. They were assessed again after enzymatic cleavage to produce Fab fragments and after labeling with 99mTc using a diamide dimercaptide ligand system. Modified and radiolabeled Fab fragments retained activity and specificity towards amyloid-laden blood vessels and senile plaques. A highly specific murine Mab, 10H3, was identified and characterized that fulfills criteria necessary for the development of a diagnostic imaging agent. Expansion and adaptation of these strategies may provide the methods and materials for the noninvasive analysis of AA in living patients, and permit assessment of the contribution of AA to the clinical and pathological features of AD. PMID- 1460514 TI - Synthesis and renal excretion of technetium-99m-labeled organic cations. AB - Organic cations are excreted more efficiently than organic anions in uremia suggesting superiority as renal imaging agents. In this study, three 99mTc labeled cationic cyclam complexes were synthesized and their renal clearance quantified in rats. The complexes are cleared at a rate of about 2.5-3 times that of inulin and about 60% that of p-amino-hipurate. Inhibition of 99Tc-cyclam excretion by quinine indicates transport by the organic cation process. Comparative in vivo imaging experiments demonstrated that in normal rats 99mTc cyclam reached peak renal activity 1.8 +/- 0.6 min after injection, a value intermediate between that for [131I]OIH (1.0 +/- 0) and 99mTc-MAG3 (2.8 +/- 0.6). In rats injected with the acute nephrotoxin cisplatin, the times to peak were lengthened with the relative order being 99mTc-cyclam > 99mTc-MAG3 > [131I]OIH. The results demonstrate that cationic complexes may be useful for renal imaging diagnostic applications. PMID- 1460515 TI - Radiotoxicity of some iodine-123, iodine-125 and iodine-131-labeled compounds in mouse testes: implications for radiopharmaceutical design. AB - In this work, spermhead survival in mouse testis was used to investigate the radiotoxicity of several intratesticularly localized radioiodinated pharmaceuticals. Radioiodines that decay by electron capture and/or internal conversion (123I, 125I) as well as by beta- decay (131I) were coupled to pharmaceuticals that selectively localize in different cell compartments. Dose response curves yield D37 values of 62 cGy, 75 cGy, 61 cGy and 7.7 cGy for 123IMP (N-isopropyl-p-iodoamphetamine), 131IdU (iododeoxyuridine), H131IPDM (N,N,N' trimethyl-N'-(2-hydroxyl-3-methyl-5-iodobenzyl)-1,3-propanediami ne) and 125IdC (iododeoxycytidine), respectively. At 37% survival, the relative biological effectiveness (RBE) of these radiochemicals, when compared to the pure gamma emitting radiochemical 7Be-chloride (D37 = 65 cGy), are 1.0, 0.89, 1.1 and 8.4, respectively. Intratesticular 7Be, with an effective half-life of 430 hr in the organ, was used as the source of reference radiation to determine the RBE values because it solely emits 477 keV gamma rays, and the dose to the testis is delivered chronically, as in the case of the other radiocompounds. Subcellular distribution studies show that all of the cellular activity is localized in the cytoplasm in the cases of 123IMP and H131IPDM, while virtually all of 131IdU and 125IdC were bound to DNA in the cell nucleus. In agreement with our earlier in vivo studies, these data show that subcellular distribution plays a key role in the radiotoxicity of Auger electron emitters such as 123I and 125I, and has no role for beta emitters such as 131I. These findings may have implications in the design of radiopharmaceuticals for both diagnosis (localize Auger emitter in cytoplasm of cell) and therapy (localize Auger emitter in cell nucleus). PMID- 1460516 TI - Noninvasive detection of hypoxic myocardium using fluorine-18-fluoromisonidazole and positron emission tomography. AB - Fluoromisonidazole (FMISO) is metabolically trapped in viable cells as a function of reduced cellular pO2. Therefore [18F]-FMISO is potentially useful for evaluating patients with hypoxic but viable myocardium. The goal of this study was to investigate [18F]FMISO uptake in ischemic myocardium non-invasively using positron emission tomography (PET). Studies were performed in 10 open-chest dogs subjected to either complete (Group 1, n = 5) or partial (Group 2, n = 5) occlusion of the left anterior descending coronary artery. The tracer was administered by intravenous bolus following the onset of ischemia and serial PET images were acquired for the next 4 hr. In Group 1, viability was assessed using histochemical staining (nitroblue tetrazolium, NBT) and 99mTc-pyrophosphate (Tc PYP). In Group 2, viability was assessed using measurements of regional wall motion, histochemical staining and histology (two animals). In each study, PET images obtained at times between 2 and 4 hr postinjection showed specific enhancement of tracer activity in the distal anterior wall and apex of the left ventricle. At 4 hr, the tissue-to-blood pool count ratio was significantly higher in ischemic regions; 1.8 +/- 0.4 for Group 1 and 1.6 +/- 0.2 for Group 2 versus 1.0 +/- 0.1 in nonischemic regions. Postmortem tissue sampling of Group 1 hearts showed significant FMISO retention in samples without evidence for infarction, either by NBT or Tc-PYP deposition, as well as in more severely ischemic regions. In Group 2 animals, FMISO was retained in myocardial regions with reduced blood flow (microspheres), which exhibited improved contraction following reperfusion. We conclude that PET imaging of [18F]FMISO is a promising technique for the noninvasive identification of viable hypoxic myocardium. PMID- 1460517 TI - Technetium-99m-HMPAO cerebral perfusion scintigraphy: considerations for timely brain death declaration. AB - The lipophilic cerebral perfusion agent 99mTc-hexamethylpropylene amine oxime (HMPAO) is increasingly used to demonstrate the absence of blood flow for the declaration of brain death. We report a case that illustrates how the timing of such studies is important when organ harvesting is the underlying emergent indication. If performed too early, a study showing the presence of cerebral perfusion may not expedite the declaration of brain death, but instead may complicate patient assessment and unnecessarily delay the process. PMID- 1460518 TI - Brain death: a diagnostic dilemma. PMID- 1460519 TI - Complications, sequela and dosimetry of iodine-131 therapy for thyroid carcinoma. PMID- 1460520 TI - An assessment of factors which influence the effectiveness of the modified in vivo technetium-99m-erythrocyte labeling technique in clinical use. AB - This study assessed factors which may contribute to suboptimal image quality when the modified in vivo erythrocyte labeling technique is used with standard clinical 99mTc activities. For each assessment duplicate or triplicate blood specimens were withdrawn from > or = 10 patients, into syringes containing 700 900 MBq 99mTc as pertechnetate. After incubation the percent of 99mTc which was not bound to erythrocytes at blood re-injection time (%Unbound 99mTc), was measured and compared when one of four factors was varied. The most significant results, in descending order of measured effect were: [table: see text] Our data suggest that the requirements for optimal erythrocyte labeling with standard clinical 99mTc activities are: (A) Erythrocyte tinning time between 10 and 30 min; (B) blood volume > or = 3 ml; (C) blood incubation time > or = 20 min; and (D) Generator ingrowth time < or = 24 hr. PMID- 1460521 TI - Spatially dependent deadtime losses in high count rate cardiac PET. AB - Cardiac PET scans result in nonhomogeneous distributions of activity within the body, which might lead to great variations in singles rates around the detector ring. Conventional deadtime correction algorithms assume that the singles rates are uniform. This paper investigates singles nonuniformities during several typical cardiac scanning protocols (bolus injections of 15O-water and 82Rb, slow infusion of 18F-FDG and static imaging with FDG) and estimates how such nonuniformities might affect quantitative data. Nonuniformity was observed in all studies and was described by an asymmetry index which increased to 58% during bolus water injection, the most inhomogeneous study. These results are valid for any scanner with a ring diameter of approximately 78 cm and are independent of the amount of activity injected. Deadtime losses depend on the amount of activity and on the scanner type. Nonhomogeneities in singles can be shown to produce spatially dependent deadtime correction factors; for our scanner, these were seen to differ by up to 16% from the mean deadtime correction during bolus water injection. To demonstrate the distortions generated by average deadtime correction, the activity distribution during a clinical cardiac study was simulated using a phantom. A simple local deadtime correction and its implementation on our system are described, and the resulting improvements in both absolute and relative quantitation of the phantom study are shown. PMID- 1460522 TI - SPECT quantification: a simplified method of attenuation and scatter correction for cardiac imaging. AB - The quantitative and visual interpretation of SPECT myocardial perfusion images is limited by physical factors such as photon attenuation, Compton scatter, and finite resolution effects. A method of attenuation correction is described for use in nonhomogeneous media and applied to cardiac SPECT imaging. This method, termed multiplicative variable attenuation compensation (MVAC), uses tissue contours determined from segmentation of a transmission scan to assign a priori determined attenuation coefficients to different tissue regions of the transaxial images. An attenuation correction map is then constructed using a technique inspired by Chang's method that includes regionally dependent attenuation within the chest cavity and is applied after reconstruction by filtered backprojection. Scatter correction using the subtraction of a simultaneously acquired scatter window image enables the use of narrow beam attenuation coefficients. Experimental measurements to evaluate these methods were conducted for 201Tl and 99mTc SPECT using a homomorphic cardiac phantom. Finite resolution effects were included in the evaluation of results by computer simulation of the three dimensional activity distribution. The correction methodology was shown to substantially improve both relative and absolute quantification of uniform and nonuniform regions of activity in the phantom's myocardial wall. PMID- 1460523 TI - Simultaneous acquisition of emission and transmission data for improved thallium 201 cardiac SPECT imaging using a technetium-99m transmission source. AB - Transmission computed tomography (TCT) data provides useful complementary information to single-photon emission computed tomography (SPECT) reconstructions, especially for cardiac studies. In particular, TCT data has been used to correct for nonuniform attenuation in the chest. Typically the transmission data are acquired in a separate acquisition, but simultaneous acquisition is preferable both to save time and to avoid difficulties involved with registration. In this work, we present a technique for simultaneously acquiring 201Tl SPECT and TCT data using a 99mTc sheet source that requires only minor equipment modifications. The use of these isotopes results in cross contamination of the emission and transmission data. We present a practical technique to compensate for this contamination using post-acquisition image processing. This technique was evaluated by performing phantom and patient studies. The resulting images compare well with data obtained from separate emission and transmission studies. PMID- 1460524 TI - Mean time parameters reveal differences in the pharmacokinetics of indium-111 and iodine-131-labeled B72.3 monoclonal antibody. PMID- 1460525 TI - U.S. policy on low-level radioactive waste challenged. PMID- 1460526 TI - DOE research appropriations scorecard. PMID- 1460527 TI - Saluting the National Birth Center Study. PMID- 1460528 TI - The National Birth Center Study. Part III--Intrapartum and immediate postpartum and neonatal complications and transfers, postpartum and neonatal care, outcomes, and client satisfaction. AB - This is the final article of the three-part report of the National Birth Center Study. Eight percent of the mothers or infants had serious complications; 16% were transferred, 12% before and 4% after the deliveries. Fifteen percent of transfers were emergencies. Nulliparous women were much more likely than parous women to experience dystocia, be transferred, or have cesarean sections. Seventy five percent of the nulliparous women gave birth in the centers, compared with 95% of the parous women. Eighty-four percent of the women had at least one postpartum home or office visit. There were 11,814 mothers, no maternal deaths, and 15 intrapartum/neonatal deaths (1.3/1,000 births, 0.7 excluding congenital anomalies). Postterm deliveries with macrosomic infants, placental abruption, sustained fetal distress, and thick meconium were associated with high mortality. Mortality was very low for those not transferred and much lower for transfers during labor as compared with those after the delivery. Women with no medical/obstetric risk factors had the lowest rates of transfers and serious complications. Except for postterm pregnancies, the intrapartum/neonatal mortality rate for birth center clients was not higher than rates from studies of low-risk hospital births, and the cesarean section rate was lower. There is no evidence that hospitals are a safer place for low-risk births. PMID- 1460529 TI - The Yolo County Midwifery Service. A descriptive study of 496 singleton birth outcomes, 1990. AB - The Yolo County Midwifery Service was begun in January 1989 to serve pregnant low income women who were denied care by local obstetricians. In 1990, 58% of women served were Latina and 33% were Anglo-white. Their mean age was 24.5 +/- 5.5 years, and their mean level of education was 9.9 +/- 3.5 years. Thirty-seven percent were nulliparous. All deliveries were at the only hospital in the county with a maternity service. To evaluate the effectiveness of nurse-midwifery care in this sample, a prospective study of the service's 496 singleton birth outcomes during 1990 was undertaken. Although the cesarean rate in 1990 for the obstetricians not associated with the midwifery service at this hospital was 20.6%, the midwifery clients experienced a primary cesarean birth rate of 3.7% and a total rate of 6.7%. Instrument-assisted deliveries took place for 1.0% of births. The success rate for women attempting vaginal birth after cesarean was 87.2%. Delivery over an intact perineum occurred for 51.8%. Preterm birth was experienced by only 1.0% of the women. A newborn birth weight of < 2,500 g occurred in 2.4% of births. Occult cord prolapse preceded a single neonatal death, resulting in a perinatal and neonatal death rate of two per 1,000. These data add to the growing body of information about nurse-midwifery in which that care is found to be a safe, well-accepted, and cost-effective adjunct to existing obstetric care services. PMID- 1460530 TI - Hematocrit values during pregnancy in a nurse-midwifery caseload. AB - This article reviews the normal hematologic changes in pregnancy and the kinetics of iron metabolism. The differences between iron depletion and anemia are described. The hematocrit levels of a nurse-midwifery caseload in a tertiary-care setting are described and compared with recently published population norms. Hematocrits of the sample compared favorably to the population hematocrits until 24 weeks' gestation, when the sample hematocrit mean became statistically lower and remained that way throughout pregnancy. Further analysis was done on the sample hematocrits, comparing differences in parity, age, pregnancy spacing, and AS versus AA hemoglobin. Parous women with a pregnancy interval > 12 months had a higher mean hematocrit than nulliparous women. Mean hematocrits of age groups varied significantly only at the 29-32-week interval, with women younger than 18 having lower mean hematocrits than those > or = 18. A trend of women with AS hemoglobin having higher hematocrits than women with AA hemoglobin was identified, reaching statistical significance at the 29-32-week interval. PMID- 1460531 TI - Evaluation of research studies. Part II: Observational studies. AB - Clinical practice is often based on the results of research. Critical evaluation of research studies is important if appropriate conclusions are to be drawn. In this series of columns, we review principles of research methodology and statistical analysis. Our intent is to assist certified nurse-midwives in understanding the relative merits of the research they read and use. This paper, the second of the series, will review issues pertinent to observational study design. PMID- 1460532 TI - No-bridge of Drosophila melanogaster: portrait of a structural brain mutant of the central complex. AB - The mutant no-bridge (nobKS49) has its name from a structural defect in the protocerebral bridge of the central complex. This rod-shaped neuropil in nobKS49 has a large gap at the sagittal midplane, with some of the missing material accumulated more laterally. Mutant nob flies have a reduced maximal and average walking speed. Leg coordination is disturbed during turning but not while walking straight. Motivation for walking is low and steps are small due to slow forward swinging of the legs. Flies spontaneously may pass into an autistic (and possibly spastic) state in which they can move their legs and even perform cleaning movements but do not walk or fly. They spontaneously recover if left undisturbed. Gynandromorph experiments place the focus of the walking defects into the head. Mutant flies have a reduced tendency to escape when mechanically stimulated. In a brightly lit arena they do not avoid a black square above the horizon and they are negatively phototactic. In tethered flight optomotor responses are normal but the amplitude of spontaneous torque modulations as well as the number of torque spikes are reduced. If a single black bar is slowly rotated around the fly, the normal response pattern is observed. It vanishes, however, at moderately fast angular velocity at which the wild type still is fully responsible. The behavioral defects support the notion that the protocerebral bridge is part of a higher center for the regulation of behavior. PMID- 1460533 TI - A mammalian homologue of a transcript from the Drosophila pecanex locus. AB - The Drosophila pecanex locus contains a maternal-effect neurogenic gene. A homologue of this gene has not yet been described in mammals or other organisms. We report here a partial complementary DNA clone from rat brain mRNA that encodes sequences which are very similar (83% over 189 amino acids) to a portion of sequence encoded by a transcript from the Drosophila pecanex locus [LaBonne, S.G., Sunitha, I and Mahowald, A.P. (1989) Dev. Biology 136: 1-161]. PMID- 1460534 TI - Ki67--structure, function, and new antibodies. PMID- 1460535 TI - KiS1--a novel monoclonal antibody which recognizes proliferating cells: evaluation of its relationship to prognosis in mammary carcinoma. AB - Immunohistochemical staining with a novel monoclonal antibody, KiS1, which recognizes a cell cycle-associated antigen, was investigated in 142 cases of stage I and II invasive breast carcinoma. KiS1 staining indices were compared with disease-free interval, overall survival, and post-relapse survival. Using a semi-quantitative method of assessment, we found that tumours with a high level of staining (34/142, 24 per cent) had a significantly worse prognosis than those with a low level of staining (108/142, 76 per cent). Significant correlations were found between KiS1 staining and disease-free interval (P < 0.001), overall survival (P < 0.001), and post-relapse survival (P = 0.008). A more time consuming, quantitative method of assessment gave similar results. Cox multivariate analysis showed these results to be independent of nodal status, histological type, and grade of tumour (P = 0.01). We conclude that KiS1 is a valuable new antibody which affords useful prognostic information in breast carcinoma. As it can be used in formalin-fixed, paraffin-embedded material, it may be of particular use in the study of small lesions such as those identified in the Breast Cancer Screening Programme. PMID- 1460536 TI - Production of a monoclonal antibody (IND.64) identifying a cell cycle-associated antigen using spleen cells from nude mice bearing Ichikawa tumour. AB - Using spleen cells from athymic nude mice grafted with Ichikawa tumour, we have generated the monoclonal antibody IND.64, which detects a proliferation associated nuclear antigen. Immunoblotting analysis with IND.64 showed a double band with apparent molecular weights of 395 and 345 kD. In normal human tissues, the antigen detected by IND.64 was expressed only by the nuclei of proliferating cells, such as germinal centre cells of reactive lymph nodes, cortical thymocytes, the basal layer of the skin, and proliferative compartments of the stomach, small intestine, and colon. IND.64 did not react with cells known to be non-proliferative or to show only a low turnover, such as cells of the kidney, liver, smooth muscle, cardiac muscle, and brain. The expression of this antigen during the cell cycle was determined using two approaches: IND.64 immunostaining of synchronized adult bovine aortic endothelial cells and flow cytometric analysis of double-labelled PHA-stimulated peripheral mononuclear blood leucocytes with a DNA marker and IND.64. The antigen recognized by IND.64 was found to appear in the late G1 phase, and persisted in phases S, G2, and M, but was absent in the G0 and early G1 phases. IND.64 was further investigated in different tumour types to evaluate the correlation between the percentage of IND.64-positive cells (IND.64 index) and the histological grade. In non-Hodgkin's lymphomas, an excellent correlation was found between the percentage of IND.64 positive cells and the cytomorphological grade. In nodular sclerosis and mixed cellularity Hodgkin's disease, a high number of Reed-Sternberg cells were positive with IND.64. The non-lymphoid neoplasms investigated showed a variable percentage of positive cells. IND.64 appears to be a promising tissue marker to complement the evaluation of prognosis in human cancer. PMID- 1460537 TI - Morphometry of gastric carcinoma: its association with patient survival, tumour stage, and DNA ploidy. AB - Morphometric image analysis of nuclear features was performed on tissue from 46 patients who had had curative resections for gastric cancer. Clinical, pathological, flow cytometric, and follow-up data were available for these patients, which were drawn from a larger, previously reported series. The morphometric data were compared with patient survival, clinico-pathological status, and DNA ploidy. Univariate survival analysis revealed that morphometric parameters were not significantly related to survival, but examination of clinico pathological data showed lymph node involvement, involvement of the resection margin, and lymphatic invasion to be significantly associated (P < 0.01) with patient prognosis. Multivariate survival analysis using the Cox model found only lymph node and resection margin involvement to be independently related to survival. Comparison of morphometric results with the clinico-pathological parameters showed various features, relating to nuclear size, and its variation to be significantly associated (P < 0.01) with the presence of lymphatic invasion, resection margin involvement, and tumour pattern (intestinal/diffuse). A comparison of morphometry with flow cytometric analysis in these cases showed that nuclear size was not significantly related to either DNA aneuploidy or the DNA proliferative index. PMID- 1460538 TI - Adhesion receptors of intimal and subintimal cells of the normal synovial membrane. AB - The distribution of cell adhesion molecules (CAMs) and matrix proteins in the normal synovium of four subjects was studied by immunohistology in order to determine the factors governing the cellular and tissue organization of the intimal and subintimal compartments. Basement membrane proteins, laminin, and collagen type IV, as well as vitronectin and fibronectin, were identified in the intima and there was corresponding expression of integrin and non-integrin receptors (e.g., CD29, CD49b, CD49d, CD49e, CD49f, CD51, CD61, CD44) for these matrix proteins. There were notable differences in CAM expression between intimal, subintimal, and vascular compartments of the synovial membrane. Phenotypic heterogeneity for CAMs involved in cell-cell interactions, particularly CD11a, CD11b, ICAM-1, and HLA-DR, was also present. The range of CAMs expressed by synovial and endothelial cells not only indicates a structural role for these antigens, but also suggests that they may control leucocyte traffic into the membrane, including recruitment of cells into the synovial lining. PMID- 1460539 TI - Heparin causes partial removal of glomerular antigen deposits by a mechanism independent of its anticoagulant properties. AB - We have previously reported that heparin can enhance the removal of antigen from the glomeruli of rats with chronic serum sickness glomerulonephritis. We have performed two studies to investigate the relevance of anticoagulation to this effect. The first experiment was essentially a repeat of those described before, but instead of using heparin, anticoagulation was achieved using Ancrod, which causes depletion of fibrinogen. The amount of antigen in the glomeruli of these rats at the end of the experiment did not differ from controls. In the second experiment, both kidneys were excised from rats with glomerulonephritis induced by a radiolabelled cationic antigen. Of each pair of kidneys, one was perfused for 30 min at 5 ml/min with Hank's balanced salt solution (HBSS) at 37 degrees C. The other was perfused with HBSS to which a total of 4500 units of heparin had been added. The antigen content of isolated glomeruli was subsequently measured. In every case, the kidney perfused with heparin had less antigen per glomerulus than the control contralateral kidney. The ability of heparin to enhance removal of glomerular immune complex deposits is therefore not mediated by anticoagulation. PMID- 1460541 TI - Neuropathology. PMID- 1460540 TI - Isologous monoclonal antibodies can induce anti-GBM glomerulonephritis in rats. AB - Injection of isologous monoclonal antibodies (SR2, SR3) caused anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM nephritis) in WKY/NCrj rats. The antibodies were obtained from hybridoma cells derived from fusion of the spleen of a nephritic WKY/NCrj rat injected with rat solubilized renal basement membranes with adjuvant, and mouse SP2-myeloma cells. They belonged to the rat IgG2a subclass and bound to rat kidney in a linear pattern along the glomerular and tubular basement membranes. Histological changes in glomeruli were detected at day 1 after the injection; proteinuria with haematuria appeared on day 2; and proteinuria became severe and reached a plateau by day 5. These results demonstrate that anti-GBM nephritis can even be induced by an isologous monoclonal antibody and that the rat IgG2a subclass is at least nephritogenic. The experimental model of anti-GBM nephritis with isologous monoclonal antibodies makes it possible and easier to analyse further the mechanism of anti-GBM nephritis. PMID- 1460542 TI - Structure, function and organization of antenna polypeptides and antenna complexes from the three families of Rhodospirillaneae. AB - Comparative primary structural analysis of polypeptides from antenna complexes from species of the three families of Rhodospirillaneae indicates the structural principles responsible for the formation of spectrally distinct light-harvesting complexes. In many of the characterized antenna systems the basic structural minimal unit is an alpha/beta polypeptide pair. Specific clusters of amino acid residues, in particular aromatic residues in the C-terminal domain, identify the antenna polypeptides to specific types of antenna systems, such as B880 (strong circular dichroism (CD)), B870 (weak CD), B800-850 (high), B800-850 (low) or B800 820. The core complex B880 (B1020) of species from Ectothiorhodospiraceae and Chromatiaceae apparently consists of four (alpha 1 alpha 2 beta 1 beta 2) or three (2 alpha beta 1 beta 2) chemically dissimilar antenna polypeptides respectively. There is good evidence that the so-called variable antenna complexes, such as the B800-850 (high), B800-850 (low) or B800-820 of Rp. acidophila, Rp. palustris and Cr. vinosum, are comprised of multiple forms of peripheral light-harvesting polypeptides. Structural similarities between prokaryotic and eukaryotic antenna polypeptides are discussed in terms of similar pigment organization. The structural basis for the strict organization of pigment molecules (bacteriochlorophyll (BChl) cluster) in the antenna system of purple bacteria is the hierarchical organization of the alpha- and beta-antenna polypeptides within and between the antenna complexes. On the basis of the three domain structure of the antenna polypeptides with the central hydrophobic domain, forming a transmembrane alpha helix, possible arrangements of the antenna polypeptides in the three-dimensional structure of core and peripheral antenna complexes are discussed. Important structural and functional features of these polypeptides and therefore of the BChl cluster are the alpha/beta heterodimers, the alpha 2 beta 2 basic units and cyclic arrangements of these basic units. Equally important for the formation of the antenna complexes or the entire antenna are polypeptide-polypeptide, pigment-pigment and pigment-polypeptide interactions. PMID- 1460543 TI - Core mutations of Synechococcus sp. PCC 7002 phycobilisomes: a spectroscopic study. AB - Three cyanobacterial strains harboring mutations affecting phycobilisome (PBS) cores were studied using steady state absorption and fluorescence and time resolved fluorescence. The apcF mutant, missing beta 18, and the apcDF mutant, missing both alpha APB and beta 18, showed only small spectroscopic differences from the wild-type strain; their PBS emission was blue shifted by 10 nm, whereas their absorption spectra and time-resolved fluorescence kinetics were virtually unchanged. The third mutant studied was the apcE/C186S mutant in which the chromophore-binding cysteine-186 in the LCM99 polypeptide has been substituted with serine. The apcE/C186S mutant contained a modified chromophore which significantly changed the spectroscopic properties of the PBS complex. The apcE/C186S PBS absorbed more than the wild-type strain at 705 nm, and the emission spectrum gave two peaks at 660 nm and 715 nm. The time-resolved kinetics of the apcE/C186S mutant PBS were also significantly altered from those of the wild-type strain. PMID- 1460544 TI - Effect of volatile thiol compounds on protein metabolism by human gingival fibroblasts. AB - The levels of volatile sulphur compounds (VSC) in periodontal pockets and mouth air have been found to correlate with severity of the disease process. The purpose of this study was to examine the influence of hydrogen sulphide and methyl mercaptan on protein metabolism of human gingival fibroblasts. The incorporation of labelled amino acids into protein was used to evaluate effects on total protein content. Changes in collagenous protein concentration were monitored by release of radioactivity following collagenase digestion as well as direct analysis of hydroxyproline. Both thiols were found to reduce total protein synthesis, with mercaptan exerting a greater adverse effect. In cultures exposed to mercaptan, total protein was reduced by 35%. The changes in total protein were accompanied by a corresponding decrease in collagenase-digestible protein. Hydroxyproline analysis of CH3SH-exposed cultures confirmed the changes associated with collagenous proteins. It indicated that in comparison to the controls the CH3SH-exposed cultures had a 70% reduction in collagen which resulted from a combined effect of suppressed synthesis and increased rate of collagen degradation. The possibility of thiol reaction with collagen was determined using in vitro systems in which type I collagen was reacted with varying concentrations of [35S]-H2S. The carboxymethyl (CM) cellulose assays of resulting reaction mixtures indicate that [35S]-radioactivity was incorporated directly into alpha 1, alpha 2, beta 11, beta 12 peptide chains. Furthermore, upon exposure of collagen to elevated H2S concentrations, the H2S converted some of the acid-soluble collagen to a more soluble product which could be extracted in neutral salt and analyzed by CM-cellulose chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460546 TI - Relationship between bacterial counts, microbial vitality and the accumulation of supragingival dental plaque in humans. AB - Comparisons between plaque index (PlI) and bacterial counts have been made already; however, these did not take into account the area used for plaque sampling. The objective of the present study was to determine the correlation between the PlI score, the number of bacteria and the bacterial plaque vitality when dental plaque was repeatedly sampled from the same area in each subject during early plaque accumulation. Between intervals of optimal oral hygiene, 10 participants refrained from all oral hygiene measures for periods of 1, 2, 3, 4 and 5 days. The PlI was recorded on the vestibular surface of all first premolars as local PlI:LS. For statistical reasons, the scores of the independent variable LS were added for each subject giving LS* values ranging from 0 to 8. The plaque sampled from this specific surface was circumscribed by the marginal gingiva and an acrylic splint, giving reproducible areas for plaque collection. Total microscopic bacterial counts (BC), colony forming units of anaerobes (CFUan) and aerobes (CFUae), and proportions of vital bacteria (VF) were compared with LS* values. BC and LS* values were strongly correlated. CFUan and CFUae increased significantly with LS*, but this increase was higher for LS* 0 to 4 than for LS* 4 to 8. The ratio between vital and dead microorganisms, assessed by two different methods, was low when an LS* of 0 was recorded, with higher ratios registered for LS* values 4 and 8. PMID- 1460545 TI - Fine structure of adrenergic nerve fibers in human periodontal ligament. AB - The presence of adrenergic nerve fibers was demonstrated ultrastructurally in the human periodontal ligament obtained from extracted premolar teeth from 8 young patients. The nerve endings were located close to arterioles. The results suggest that they seem to control blood flow in the human periodontal ligament. PMID- 1460547 TI - Influence of temperature and foil hardness on interocclusal tactile threshold. AB - Determinations of interocclusal tactile threshold levels so far have involved neither appropriate psychophysical approaches nor an assessment of the mechanical and thermal properties of the foils used. Twenty subjects (12 females) aged 18 to 50 (mean age 35) were tested for their absolute threshold level (RL). Both the method of limits and the staircase method were applied to determine the active or passive RL. For the active RL assessment, foils of different thicknesses were placed between edge-to-edge opposed incisors during gentle biting. Inner ear receptors of the blindfolded subjects were blocked by broad band noise applied through earphones, because vibrations induced by occlusal contact and conducted through bone might be perceived by these receptors. The foils presented were aluminum (Al), tin (Sn), polyester (PE) and calibrated steel (St) (thickness ranging from 8 to 50 microns) which offer different physical and thermal properties. The range of RL of the group varied between 8 microns for aluminum to 46 microns for polyester for 50% correct assessments. Increasing the foil temperature from room temperature (20 degrees C) to body temperature (35 degrees C) significantly increased the RL for conducting materials (one-way blocked ANOVA). These results indicate that temperature exchange takes place while presenting conducting foils at 20 degrees C (cold stimulus) interocclusally, which influences the RL by activating thermosensitive receptors. The passive RL determination with classical von Frey-hairs resulted in a mean axial RL of 3.0 g. Both psychophysical RL assessments (method of limits, staircase method) gave reproducible and similar results as ascertained by ANOVA. Furthermore, a positive correlation was established between active and passive RL (Pearson correlation test).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460548 TI - The mechanisms of Eikenella corrodens aggregation by salivary glycoprotein and the effect of the glycoprotein on oral bacterial aggregation. AB - The mechanism of aggregation of Eikenella corrodens 1073 with E. corrodens aggregating factor (EcAF) which was purified from submandibular-sublingual (SM SL) saliva was investigated. Heating (100 degrees C, 10 minutes) or protease treatment of E. corrodens cells abolished the aggregating activity. The aggregation was inhibited by adding N-acetyl-D-galactosamine (GalNAc) and saccharides which contain a galactose residue at the non-reducing end. The aggregating activity was sensitive to EDTA and was restored by Ca2+ but not by Mn2+ or Mg2+. Neuraminidase treatment of EcAF increased their ability to aggregate. E. corrodens, suggesting that the sialic acids on EcAF interfere with aggregation. These data suggest that the aggregation of E. corrodens 1073 with EcAF is mediated by specific interactions between a bacterial cell surface lectin like substance and a complementary GalNAc-like receptor. EcAF also aggregated 16 strains of oral bacteria including periodontopathic bacteria such as Porphyromonas (Bacteroides) gingivalis 381 and Actinobacillus actinomycetemcomitans ATCC29522; however, those aggregations were not inhibited by GalNAc. Therefore, EcAF appears to have more than two types of bacterial binding site and plays important roles in accumulation of dental plaque by forming a complex network of plaque bacteria including periodontopathic strains. PMID- 1460549 TI - Tetracycline administration increases protein (presumably procollagen) synthesis and secretion in periodontal ligament fibroblasts of streptozotocin-induced diabetic rats. AB - Streptozotocin-induced, insulin-deficient diabetic adult rats were daily administrated either minocycline or a chemically-modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week time period; untreated diabetic and non-diabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The upper and lower mandibles of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by fibroblasts in the periodontal ligament (PDL) of molars. In the non-diabetic controls, at 20 min after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of PDL fibroblasts. At the 4-h time period, most of the label was present over the collagen fibers around these cells. In contrast, PDL fibroblasts in the untreated diabetic rats showed marked abnormalities ultrastructurally and minimal uptake (20 min) and secretion (4 h) of labeled proline. At both time periods, in both minocycline- and CMT-treated diabetic rats, fibroblasts were structurally more normal and the radioprecursor was localized in the fibroblasts and the PDL matrix in a pattern similar to that seen in the control rats. These results suggest that the diabetes-induced structural abnormalities and suppression of synthesis and secretion of protein (presumably collagen and its precursor) by PDL fibroblasts can be restored to near-normal by administration of a tetracycline and that this effect is mediated by a non antimicrobial property of this family of antibiotics. PMID- 1460550 TI - Living arrangements and nutrient intakes of healthy women age 65 and older: a study in Manhattan, Kansas. AB - One hundred healthy women over age 65 were recruited for a study to determine differences in nutrient intakes by living arrangement and to examine the effect of demographic characteristics, health habits, and social contacts on nutrient intakes. There were significant differences (p < 0.05) in the mean intakes for calcium and riboflavin between women living alone and women living with a spouse. There were no significant differences in health habits by living arrangement, but women living alone were more likely to have fewer social contacts than women living with a spouse (x2 = 38.25; p < 0.001). Education, physical activity, and smoking were the most important predictors of nutrient intakes. PMID- 1460551 TI - Nutrition promotion for mature adults: a case study in peer education. AB - The peer education model, which enables trained learners to instruct their peers, was tested in a case study involving senior citizens in a nutrition education program. The case study approach, using action research, was chosen because the project involved the description and analysis of a unique group of 32 mature adults. Topics selected for presentation in the three two-hour sessions were selected by open consensus of the entire participating body. Six members of the group volunteered to engage in a preliminary training program. These individuals became known as volunteer peer educators (VPE), who subsequently took full responsibility for disseminating the nutrition information to their peers. Educational materials to meet the goals of the program were compiled by the researcher in a resource manual for each of the volunteer peer educators. Techniques of participant observation for data collection and qualitative analysis were used. The satisfactory implementation of the program was due in great part to group selection of the learning episode; to a relaxed atmosphere; to enthusiasm on the part of the VPE; to the availability of a good resource manual and a facilitator who provided a strong organizational framework. The peer education model was found to be a particularly useful tool in providing nutrition information to a much broader sector of the senior population than can be currently reached via public health programs. PMID- 1460552 TI - Project director characteristics in the Elderly Nutrition Program. AB - The federally funded Elderly Nutrition Program (ENP) began in 1972, authorized under Title 7 of the Older Americans Act. Its purpose was to serve elders, targeting those in greatest social and economic need. This article describes the characteristics of the Nutrition Project Directors in the ENP through data gathered by a questionnaire completed by a random sample of 430 directors across the nation. One important finding was that directors of programs serving large numbers of low-income or minority elders tended to have less education and commanded lower salaries than directors serving fewer poor and minority elders. In addition, while a higher proportion of these directors were minority members, numbers of nonwhite Nutrition Project Directors remains low. PMID- 1460553 TI - Sous vide processed foods: are they safe for the elderly? AB - Demographic trends and market analyses indicate that Americans' interest in convenience foods that are nutritious, safe, and high quality will influence the food industry into the next century. The increase in individuals over 55 plus working women, and the changing family have caused the food industry to develop a new generation of foods. One of the processes, sous vide, is an advanced method where fresh foods are vacuum sealed in impermeable plastic, cooked at low temperature in circulating water, and chilled and held at refrigerator temperature for up to three weeks. Nutritionists and food scientists have concerns about the food safety of sous vide products and the possible increase in food borne illnesses. Continued research is needed for the food industry to deliver safe, nutritious foods, particularly to the elderly. PMID- 1460554 TI - Affect, personality, and social activity. AB - These studies examined relations between social activity and state and trait measures of Positive and Negative Affect. In Study 1 Ss completed scales relevant to 3-factor models of personality and a weekly mood and social activity questionnaire for 13 weeks. In Study 2 Ss completed measures of the 5-factor model of personality and a daily mood and social activity survey for 6-7 weeks. In within- and between-Ss analyses, socializing correlated significantly with state measures of Positive Affect and with trait measures of Extraversion/Positive Emotionality. These relations were relatively general across various types of positive affect and social events; however, specific types of social events also were differentially related to affect. In contrast, social activity had no consistent association with measures of Negative Affect or the other personality dimensions. The results support a temperamental view of Extraversion. PMID- 1460555 TI - Repression at encoding: discrete appraisals of emotional stimuli. AB - In previous research, the emotions associated with repressors' memorial representations were found to be more discrete than those associated with nonrepressors'. In each of the 3 experiments reported here, repressive discreteness was apparent in repressors' appraisals of emotional stimuli at the time they were encoded. In 1 experiment, Ss appraised individual facial expressions of emotion. Repressors judged the dominant emotions in these faces as no less intense than did nonrepressors, but they appraised the blend of nondominant emotions as less intense than did nonrepressors. In the remaining 2 experiments, Ss appraised crowds of emotional faces as well as crowds of geometric shapes. In both crowd experiments, the repressive discreteness was evident in appraisals of crowds of emotional faces but not in appraisals of crowds of geometric shapes. The repressive discreteness effect did not appear to reflect a general repressor-nonrepressor difference in the appraisal of stimulus features. Rather, the results suggested that repressive discreteness may be constrained to appraisals of emotions. PMID- 1460556 TI - Intergenerational continuity of parental rejection and depressed affect. AB - Using survey and observational data from a sample of 451 intact families, this study used structural equation modeling to examine the intergenerational continuity of depressed mood and rejecting parenting. The model partially replicated the intergenerational model of Elder, Caspi, and Downey (1986) that indicates a cyclical transmission process by which parents' personality traits affect parent-child interaction, which, in turn, increases the propensity for developmental problems among offspring. The results indicated a pattern of intergenerational transmission of depressed mood through parental rejection of offspring. Multiple reporters and multiple indicators strengthen previous intergenerational findings by reducing some of the method variance biases that have been problematic in prior studies. PMID- 1460557 TI - Thinking is for doing: portraits of social cognition from daguerreotype to laserphoto. AB - From the outset, perspectives on social cognition have taken an emphatically pragmatic stance, as evident in early writing by James, Allport, Bruner, Asch, Heider, Tagiuri, and Jones. After a hiatus, during which social cognition research neglected its proper attunement to social behavior, researchers again are emphasizing that thinking is for doing, that social understanding operates in the service of social interaction. Early and recent (but not intermediate) theories have reflected a pragmatic orientation in 3 recurring themes: People are good-enough social perceivers; people construct meaning through traits, stereotypes, and stories; and people's thinking strategies depend on their goals. The pragmatic viewpoint again opens up new areas for research and theory in social cognition. PMID- 1460558 TI - Memory accessibility and probability judgments: an experimental evaluation of the availability heuristic. AB - Consistent with Tversky and Kahneman's (1973, 1974) availability heuristic hypothesis, the current study found a negative correlation between recall latency for past events and the perceived future probability of similar events. Furthermore, when the relative accessibility of memories of positive and negative events was experimentally manipulated using the Velten mood-induction procedure, the perceived future probabilities of similar events also changed in a manner consistent with the availability heuristic account. Reductions in recall latencies resulting from the mood manipulations were, as predicted, related to increases in perceived probability, and vice versa. Partial correlations indicated that this association between the observed patterns of changes in recall latencies and probability judgments could not be accounted for by the existence of independent associations between each of these effects and the magnitude of mood change. PMID- 1460559 TI - Why do people need self-esteem? Converging evidence that self-esteem serves an anxiety-buffering function. AB - Three studies were conducted to assess the proposition that self-esteem serves an anxiety-buffering function. In Study 1, it was hypothesized that raising self esteem would reduce anxiety in response to vivid images of death. In support of this hypothesis, Ss who received positive personality feedback reported less anxiety in response to a video about death than did neutral feedback Ss. In Studies 2 and 3, it was hypothesized that increasing self-esteem would reduce anxiety among individuals anticipating painful shock. Consistent with this hypothesis, both success and positive personality feedback reduced Ss' physiological arousal in response to subsequent threat of shock. Thus, converging evidence of an anxiety-buffering function of self-esteem was obtained. PMID- 1460560 TI - Controlling the uncontrollable: effects of stress on illusory perceptions of controllability. AB - Individuals' failure to exercise actual control over an event might be compensated for by trying to bolster a generalized, subjective sense of control. Control might then be sought by undertaking acts the effect of which on the environment is illusory. This observation led to the hypothesis that stress, which undermines persons' sense of control, would engender illusory perceptions of controllability. The hypothesis was tested in 3 experiments that required Ss to choose between 2 gambling forms. Although the 2 forms were essentially identical, 1 was designed to instill an illusion of control. The results showed that highly stressed Ss, compared with those who experienced low stress, preferred gambling forms that heightened perceptions of controllability. PMID- 1460561 TI - The impact of mothers' gender-role stereotypic beliefs on mothers' and children's ability perceptions. AB - The focus of this study is the relation between mothers' gender stereotypic beliefs, their perceptions of their children's abilities, and their children's self-perceptions in 3 activity domains. Approximately 1,500 mothers and their 11- to 12-year-old children responded to questions about the children's abilities in the math, sports, and social domains. It was predicted that mothers' beliefs about their children would be moderated by their gender stereotypic beliefs about the abilities of female and male people in general. As predicted, path analyses revealed that mothers' gender stereotypic beliefs interact with the sex of their child to influence their perceptions of the child's abilities. Mothers' perceptions, in turn, mediate the influence of past performance on children's self-perceptions in each domain. PMID- 1460562 TI - Social facilitation and inhibition of emotional expression and communication. AB - Does the presence of others facilitate or inhibit emotional expression? Female "senders" (n = 45) viewed 12 emotionally loaded slides either alone or with another sender while responses were secretly videotaped. In Study 1, 14 "receivers" guessed the type of slide viewed by dyads more accurately (eta = .366). In Study 2, 42 receivers viewed 10 senders with friends, 10 with strangers, and 10 alone. One dyad member was covered so that only 1 sender was visible. Analysis revealed significant effects of condition (alone, friend, or stranger; eta = .456), slide type (sexual, scenic, unpleasant, or unusual; eta = .325), and the Condition x Slide Type interaction (eta = .350). Strangers had overall inhibitory effects on communication accuracy, whereas friends had facilitative effects on some slides and inhibitory effects on others. Thus, both social facilitation and inhibition of expression occurred on the basis of the emotional stimulus and personal relationship involved. PMID- 1460563 TI - Fishy-looking liars: deception judgment from expectancy violation. AB - To explain how people judge that others are lying, an expectancy-violation model is proposed. According to the model, deception is perceived from nonverbal behavior that violates normative expectation. To test the model, 3 experiments were conducted, 2 in the United States and 1 in India. In each experiment, people described acquaintances while exhibiting weird nonverbal behaviors, such as arm raising, head tilting, and staring. Other Ss watched the videotapes of the descriptions and made deception judgments. Consistent with the expectancy violation model, both American undergraduates and Indian illiterates inferred deception from weird behaviors. Implications of the model are discussed. PMID- 1460564 TI - Disclosure and anxiety: a test of the fever model. AB - According to the fever model of Disclosure, the relationship of Disclosure (utterances that reveal subjective information) to psychological distress is analogous to the relationship of fever to physical infection: Both are indicators of some underlying disturbance and part of a restorative process. High and moderate trait anxious university students (but not the low trait anxious students) used higher percentages of Disclosure when speaking about an anxiety arousing topic than when speaking about a happy topic. With topic order counterbalanced, students tended to use more Disclosure during their 1st presentation than during their 2nd. These results support the fever model's suggestion that people tend to Disclose when they are distressed. PMID- 1460565 TI - Modeling cognitive adaptation: a longitudinal investigation of the impact of individual differences and coping on college adjustment and performance. AB - Drawing on cognitive adaptation theory, optimism, psychological control, and self esteem were explored as longitudinal predictors of adjustment to college in a sample of 672 freshmen. Although a direct effect of optimism on adjustment was found, most of the predicted effects were mediated by coping methods. Controlling for initial positive and negative mood, the beneficial effects of optimism, control, and self-esteem on adjustment were mediated by the nonuse of avoidance coping, greater use of active coping, and greater seeking of social support. Alternative models of the causal relations among these variables did not fit the data as well as the a priori mediational model. The results of a 2-year follow-up indicated that self-esteem and control predicted greater motivation and higher grades, controlling for college entrance exam scores. Implications for cognitive adaptation theory and for interventions with populations under stress are discussed. PMID- 1460566 TI - Susceptibility of a line of dolphin kidney cell culture to several herpesviruses. AB - A cell line was established from cell cultures of kidney cortex of a pantropical spotted dolphin, Stenella attenuate. The replication of 6 strains of herpesviruses was studied in the cells. Five strains of them, herpes simplex virus type I and type II, equine rhinopneumonitis virus, infectious bovine rhinotracheitis virus and Aujeszky's disease virus, were grown fairly well in showing clear cytopathic effects and plaques under agar overlay medium. PMID- 1460567 TI - Metabolism of gallate in Penicillium simplicissimum. AB - The pathway for the degradation of gallate (3,4,5-trihydroxybenzoate) by a new strain of Penicillium was examined by in vivo and in vitro cell-free systems. The organism was identified as P. simplicissimum (Oud) Thom. It grew optimally at pH 5.5 and 27 degrees C, with 11.75 mM (0.2%) gallate added to the basal salt media. Mycelia grown on gallate accumulated protocatechuate in the medium, and had inducible activity for protocatechuate 3,4-dioxygenase as determined by spectrophotometric and oxygen electrode studies. A NADPH-dependent reductase in the cell-free extract reduced gallate to dihydrogallate. Maleylacetate reductase was also detected in the gallate induced cell-free extract, while beta ketoadipate was detected as the product produced. The possible steps in the degradation of gallate are discussed. PMID- 1460568 TI - Fungal contamination, natural occurrence of mycotoxins and resistance for aflatoxin accumulation of some broad bean (Vicia faba L.) cultivars. AB - Using glucose-Czapek's and 10% NaCl glucose-Czapek's agar media incubated at 28 +/- 2 degrees C, nine genera and 18 species were identified from 10 different cultivars seed of broad bean. Aspergillus and Penicillium were the most common genera on the two types of media used. The most common fungal species were Aspergillus flavus, A. niger, A. tamarii and Penicillium chrysogenum. Thin-layer chromatographic analysis indicated that seeds of one cultivar only was naturally contaminated with aflatoxins B1, B2, G1 and G2. Nine mycotoxin-free cultivars of broad bean were examined for resistance or susceptibility for aflatoxin production when inoculated by Aspergillus flavus IMI 89717. Results obtained revealed that seeds of two cultivars were highly resistant, two cultivars showed partial resistance and the remaining were susceptible to the establishment of A. flavus and aflatoxin accumulation. The results did not show any relationship between morphological characters (colour, shape and size) and the amount of aflatoxin produced on the different broad bean seed cultivars. Also the results reveal absence of significant variation in the total nitrogen of the highly susceptible, partially resistant and highly resistant groups of broad bean seeds examined. Mean values of calcium, total phosphate and potassium of both seed coat and seed kernel of the susceptible seeds were low as compared to those of partially and highly resistant seed cultivars. The susceptible seeds contained higher levels of magnesium, zinc and sodium while the resistant seeds contained lower ones. PMID- 1460569 TI - Overexpression of a Rhodococcus erythropolis protein in Escherichia coli with immunological identity to the Rhodococcus steroid 1-dehydrogenase. Immunoelectron microscopic localization and electrophoretic studies. AB - The recombinant Escherichia coli K-12 strain chi 6060 harbouring the plasmid pYA 1201 with a gene from Rhodococcus erythropolis IMET 7030 overexpressed a protein which reacts with a monospecific antiserum against the steroid 1-dehydrogenase (Sdh) from the same Rhodococcus strain. It was shown previously that this recombinant protein exhibits no enzymatic activity. By immunogold labelling the protein was localized on ultrathin sections of the recombinant E. coli strain. After cultivation at 37 degrees C it was found within large cytoplasmic compartments (inclusion bodies). The inclusion bodies occupied 40% to 75% of the sectioned cell area. The highest amount of protein was observed after induction of the culture with isopropyl-beta-D-thiogalactopyranoside. Approximately 20% of the induced cells became enlarged (up to 5-fold of the normal size) and deformed; multiplication of the Rhodococcus protein producing cells was inhibited. After ultrasonic cell disintegration the inclusion bodies were found only in the fraction of the sedimented cell debries and did still react with anti-Sdh. When recombinant E. coli cells were cultivated at 28 degrees C, inclusion bodies appeared very seldom and the immunoreactive protein was distributed throughout the whole cytoplasm. PMID- 1460570 TI - Perspectives on entry level residency training in podiatric medicine. AB - The author presents information related to the structures of medical and podiatric residency training and statistical information regarding entry level residency positions in approved podiatric residency programs. The results of surveys of residency directors (1989 and 1990) and the residency community of interest (1990) conducted by the Council on Podiatric Medical Education are reported. Specific findings from the surveys indicated the desirability of establishing training sequences consisting of rotating podiatric residencies followed by specialty training programs but identified significant difficulties related to implementation. PMID- 1460571 TI - The residency in podiatric medicine. A brief historical overview. AB - The author provides a general overview of the development of postgraduate residency training in podiatric medicine since 1956. The evolution of residency standards and requirements of the Council on Podiatric Medical Education are discussed. Integration of specialty organizations in the residency evaluation process also are reviewed. The author notes that the current positive number of entry level residency positions available to graduates of colleges of podiatric medicine may be a dubious facade in view of increasing college enrollments and the potential conversion of rotating podiatric residencies to residencies in primary podiatric medicine. He cautions the profession not to overlook these events as it considers the development of the PGY-1 concept in the restructuring of entry level residency training. PMID- 1460572 TI - Primary care podiatric medicine and entry level residency. The new millennium. AB - The author presents the perspective that the nation's health care initiatives demand that greater attention be given to primary care providers. Inasmuch as the credibility of the podiatric medical profession must function in a health care environment dominated by allopathic and osteopathic physicians, the podiatric primary care initiative must be pursued within the guidelines and definitions for primary care that are present in all of mainstream medicine. The author argues that primary care podiatric medicine must establish itself as a specialty that stands as an equal along side of the other recognized specialties in podiatric medicine. Also, in keeping with the essential educational needs for specialty training, the development of residencies in primary podiatric medicine is crucial to assuring a credible area of special practice. PMID- 1460573 TI - Postgraduate podiatric medical educational resources in the Department of Veterans Affairs. AB - The existing podiatric medical residencies in the Department of Veterans Affairs are reviewed. The suitability of these residencies to fill a potential need for entry level programs is discussed. The financial implications of providing such training are reviewed and a plan for implementation is presented. Ninety-eight rotating podiatric residency positions currently available in Department of Veterans Affairs hospitals are prime candidates to serve as entry level PGY-1 positions. Assurances will need to be given that implementation of the PGY-1 concept must serve the best interests of the veteran patient population, and that funds will need to be allocated to pay faculty salaries and resident stipends. Congressional review of student loan forbearance policies affecting podiatric medical residents is also needed. PMID- 1460574 TI - Experience with the rotating podiatric residency/podiatric surgical residency-12 model. Twenty-four months of integrated training. AB - The author describes the positive experiences of Cranston General Hospital, Osteopathic in establishing a 24-month program, combining an entry level rotating podiatric residency and a podiatric surgical residency. The program grew from a 12-month surgical program to become a 24-month program, using expanded training opportunities available in Brown University teaching hospitals. An improved quality of care and a greater fund of knowledge for the residents are two results of the 24-month training program. Recommendations and views about developing entry level residency programs are presented. PMID- 1460575 TI - An alternative approach to the mandatory year of clinical residency training. AB - The author takes the position that a mandatory fifth postgraduate year to serve as a uniform period of clinical education for podiatric medical graduates is unnecessary. A need exists to define primary podiatric medicine as the entry level podiatric medical field of practice. The colleges of podiatric medicine are urged to deemphasize podiatric surgery while placing greater emphasis on primary podiatric care. The author believes that the colleges are responsible for preparing primary podiatric medical practitioners. Residency programs should focus on specialty training in podiatric surgery and podiatric orthopedics. PMID- 1460576 TI - The future of postgraduate podiatric medical education. Report of the consensus panel. Consensus on critical issues with a specific focus on entry level positions. PMID- 1460577 TI - The entry level residency curriculum. Proposal for discussion. AB - The author discusses the curriculum proposed for the PGY-1 residency program. The author briefly describes the activities resulting from the March 1992 residency forum that have led to a national survey of residency program directors to ascertain opinions about the critical elements of the PGY-1 residency. The elements proposed as part of the PGY-1 curriculum, including specific training experiences for 13 clinical rotations, are presented. Results of the survey will be used as a basis for discussion at a second residency forum to be held in December 1992. PMID- 1460578 TI - Sexual harassment in podiatric medical education. The residency interview process. PMID- 1460579 TI - Diabetic ulcers. PMID- 1460580 TI - Morton's neuroma. PMID- 1460581 TI - Primary prevention trial of oral cancer in india: a 10-year follow-up study. AB - Oral cancer is caused by chewing and smoking of tobacco. To assess the feasibility of primary prevention of oral cancer, two cohorts were studied in base-line surveys and then followed up annually for 10-yr in Ernakulam district of Kerala state. The intervention cohort consisted of 12212 tobacco users aged 15 yr and over, who were exposed to a concentrated program of education against tobacco use. The control cohort was a non-concurrent cohort of 6075 tobacco users studied using similar methods but with a minimal amount of advice against tobacco use. The stoppage of tobacco use increased and the incidence rate of leukoplakia decreased significantly and substantially in the intervention cohort compared to the control cohort. The decrease in the incidence of leukoplakia was indicative of the decrease in the risk of oral cancer since the two were intimately related. This study demonstrated feasibility of primary prevention of oral cancer. PMID- 1460582 TI - Melanin depigmentation of the palatal mucosa in reverse smokers: a preliminary study. AB - The melanin pigmentation in the palate of Indian reverse smokers was histologically studied in 80 biopsies, which were compared with corresponding tissue from 49 nontobacco users. The morphology of epithelium containing melanin in its basal part was normal in smokers and nonsmokers, in contrast to areas with a local melanin depigmentation of the epithelium found in some of the reverse smokers. Here an epithelial thinning, inflammation in the underlying connective tissue, and eventually a cancer was found. The histologic appearance was in accordance with the theory that as long as a smoker's melanosis or a genetic melanin pigmentation is present, melanin functions as a defence against toxic agents penetrating into the oral mucosa. PMID- 1460583 TI - Langerhans cell distribution and keratinocyte expression of HLADR in oral lichen planus. AB - Keratinocyte expression of the Class II major histocompatibility complex antigen HLADR, is seen in several inflammatory disorders of skin and mucosa, including lichen planus. The purpose of this study is to determine whether the distribution of Langerhans cells and their expression of CD4 in oral lichen planus is related to keratinocyte HLADR. The numbers of CD1- and CD4-positive Langerhans cells were compared in areas of keratinocyte HLADR and areas showing no expression in oral lichen planus and with normal oral mucosa. Cells were identified using an immunoalkaline phosphatase technique and numbers were expressed per mm epithelial surface length. In lichen planus, an increase both in the number of Langerhans cells and the numbers expressing CD4 were found in areas of keratinocyte HLADR expression compared with HLADR negative areas and with normal oral mucosa. There was no difference in the numbers of Langerhans cells or their expression of CD4 between HLADR-negative areas in LP and normal oral mucosa. These results show that the distribution of Langerhans cells is related to keratinocyte expression of HLADR and suggest that Langerhans cell entry may be enhanced in these areas. Whilst it is possible this enhancement is mediated by CD4/HLADR interaction, other molecules are also likely to be important in controlling Langerhans cell entry into oral mucosa. PMID- 1460584 TI - Relative efficacy of fluocinolone acetonide compared with triamcinolone acetonide in treatment of oral lichen planus. AB - Twenty patients with oral lichen planus and topically treated with fluocinolone acetonide in orabase 0.1% (FAO) were compared with 20 treated with triamcinolone acetonide in orabase 0.1% (TAO). During 4 wk of treatment the lesions in 13 of 19 patients could be effectively cured with FAO whereas only 8 of 19 patients were cured with TAO. These differences were statistically significant. There were no differences in blood pressure, plasma cortisol or number of circulating lymphocytes after treatment with FAO, but the number of eosinophils was reduced in every case after treatment for 6 months. There was no permanent adrenal cortical suppression after treatment for 6 months. Acute pseudomembranous candidiasis during the treatment was common but could be cured with antifungal drug in every case. This study shows that FAO in a majority of cases is an effective treatment of oral lichen planus without any serious clinical side effects apart from treatable candidiasis. PMID- 1460585 TI - Transamidase and collagenase activity in healthy and diseased human gingival tissues. AB - Transamidases are a class of calcium-dependent mammalian enzymes which cross-link proteins by catalyzing the formation of (gamma-glutamyl)-epsilon-lysine bonds. It is possible that these enzymes play an important anabolic role in tissue healing. This study was to quantitate transamidase activity in human gingival tissue and examine the relation between transmidase activity and degree of inflammation. Forty-four out of a total 120 collected human gingival specimens from healthy and diseased patients were selected based on histometric and microbiologic criteria. Specimens were minced and homogenized in 10 mM CaCl2 and then extracted for 30 min, in 50 mM tris-HCl buffer (pH 7.5) containing 100 mM CaCl2. Following low speed centrifugation at 4 degrees C, the supernatant solution was assayed for both transamidase and collagenase activities by radioactive amine incorporation, and digestion of tritiated collagen, respectively. Appreciable levels of transamidase and collagenase activities in healthy gingivae were found. These enzyme activities were significantly elevated in the diseased and healing tissues. Unlike other transamidases, calcium was required in the enzyme extraction process. PMID- 1460586 TI - [New attempts in practical training of physiology for medical students]. PMID- 1460587 TI - [Current treatment of poisoning by ingestion of caustic substances]. AB - Lesions by ingestion of corrosive substances had so far been treated at the time of sequelae. In the seventies several events modified deeply the epidemiology and the early care of these poisonings. At that time household products like highly concentrated basic and acid substances and oxidizing agents were distributed and led to an increase of the number and the severity of these intoxications. In the same time, fiberoptic endoscopy of the digestive tract played a leading part to evaluate the diagnosis and the prognosis of these poisonings at an early stage, and thus, with accurate intensive care and digestive surgery contributed to generate appropriate guidelines, according to the severity. The first step of the treatment is fasting, fluid replacement and analgesic if required. A full examination must be performed, especially in the throat even if there is no strong correlation between early clinical signs and the severity of the lesions; blood samples must be obtained to look for metabolic acidosis, hyperleukocytosis hemolysis and consumption coagulopathy which could be better indicators of the severity. Fiberoptic endoscopy of the upper digestive tract should be performed as soon as the physical and psychological patient's condition is stable; if possible before the twelfth hour and no more late than the twenty-fourth hour. It should determine the lesions: type, range and grade according to Quincy's classification modified by Mongon and Di Constanzo. Survival and healing of "extremely severe" grade intoxication can only be obtained through a surgical intervention within the first hours; a laparotomy will indicate the depth of the lesions, which is not determined by endoscopy, and will consist of Celerier's stripping method and if necessary a gastrectomy, more seldom a cephalic duodeno pancreatectomy. Only the surgical excision of necrotic tissues can prevent the occurrence of lethal complications like oesophageal or gastric perforations and septic shocks. The analysis of the literature from 1975 up to now gives us information on the methods and the results of these different therapeutic approaches. PMID- 1460588 TI - [Current status of poisoning by ingestion of caustics: apropos of a series of 49 cases]. AB - The authors report the history of 49 patients, admitted to an intensive care unit after a caustic or corrosive ingestion. This series follows a similar one, related in 1979. An update is made for early evaluation and management, based on patients classification in three groups: severe cases, moderate cases, mild cases. Clinical and biological data, treatment and outcome for the three groups are related. The frequency and gravity of these poisonings appear to be the same as in the first series, with poor prognosis for extreme emergencies and high risk of oesophageal or gastric stricture for important forms. In this population, 20% of extreme emergencies have favorable outcome with early major surgical procedure. PMID- 1460589 TI - [Fatal poisoning involving amitriptyline: toxicologic data]. AB - A fatality involving amitriptyline is described. The drug and its metabolite nortriptyline were separately quantified in various post-mortem samples, including hair. Results are discussed in the light of the existing literature. PMID- 1460590 TI - [Iodoform poisoning. 3 cases]. AB - Three cases of iodoform poisoning are described following dressings with 10% iodoform gauze (0.10 x 5 m) on extended wounds. Five, ten and sixteen days after the beginning of dressings, the patients became confuse, hallucinated, and one of them was subsequently comatose. Vomiting, fever, tachycardia with premature ventricular beats and shortening of P-R interval, slight increase of transaminases and proteinuria were observed. Within a few days (3 to 8) after the iodoform dressings were discontinued, the signs of iodoform toxicity disappeared. The toxicity of iodoform is probably unrecognized if the rarity of the observations published and the amount of iodoform gauzes annually sold are compared. PMID- 1460591 TI - Risks of flumazenil in mixed benzodiazepine-tricyclic antidepressant overdose: report of a preliminary study in the dog. AB - This preliminary study evaluates the cardiac and neurological risks associated with the sudden antagonism of benzodiazepine (BZD)--induced sedation in dogs intoxicated with tricyclic anti-depressants (TCA). Twelve dogs were anesthetized with midazolam and ventilated with room air. EEG, ECG, and arterial pressure were continuously recorded. An infusion of amitriptyline (6 dogs) or clomipramine (6 dogs) 1 mg/kg. min was maintained until signs of cardiotoxicity (QRS prolongation, hypotension or arrhythmias) occurred. The effects of a bolus of flumazenil 0.2 mg/kg were then observed until 120 minutes. In amitriptyline poisoning, BZD reversal was associated with development of convulsions in 3 dogs, with severe arrhythmias in 4 and with one death. In clomipramine intoxication, 2 dogs developed sudden fatal arrhythmias. These results show that BZD reversal may unmask the convulsant properties and increase the severity of arrhythmias induced by TCA. PMID- 1460592 TI - Operation Haven--one year on. PMID- 1460594 TI - Naval Party 1026 (SE)--first in, first out. PMID- 1460593 TI - Operation Haven. PMID- 1460595 TI - Primary Casualty Reception Ship: the hospital within--Operation Granby. AB - As the build-up of Operation Granby forces developed in the Gulf, casualty estimates indicated the need for a 100-bed hospital facility to care for the possible maritime casualties. RFA Argus, the Air Training Ship, was identified as the potential Primary Casualty Reception Ship (PCRS) and at the end of September 1990 plans were drawn up to convert the forward hangar into a two-storey 100-bed hospital in collective protection (COLPRO). In the three weeks prior to deployment, the hospital was designed, built, equipped and staffed. Argus arrived in the Gulf in mid-November as the PCRS with, all in COLPRO, a 10-bed intensive care unit (ICU), a 14-bed high dependency unit (HDU), a 76-bed low dependency unit (LDU) plus four operating tables in two theatres with full support services. The hospital was staffed by a medical team of 136 personnel and supported by the Air department with four casualty evacuation helicopters, an RN Party and the staff of the RFA. One hundred and five patients were treated of which 78 were returned to duty. Argu as PCRS spent longer in the northern Persian Gulf than any other ship, UK or US. PMID- 1460596 TI - Naval Party 1036: its role in the Gulf Conflict. AB - With the escalation of the Gulf Conflict in December 1990, there was a greater requirement for medics to support the land forces. In war, BMH Hannover becomes 32 Field Hospital RAMC, a 200 bed third line medical facility. This account describes the contribution made by Naval Party 1036 when it augmented 32 Field Hospital in Saudi Arabia in early 1991 during Operation Granby. PMID- 1460597 TI - Operation Haven. PMID- 1460598 TI - No safe haven? Kurdish relief operation April-July 1991. PMID- 1460599 TI - Kurdish relief--a nurse's view. PMID- 1460600 TI - Operation Haven--paediatric perspective. PMID- 1460601 TI - Operation Haven: surgical aspects. PMID- 1460602 TI - Decrease in enkephalinase A number in kidney membranes from hypercholesterolemic and hypertensive rats. AB - The variation of enkephalinase A number on the hypertensive and hypercholesterolemia rats kidney membranes is studied using the [3H]-acetorphan, a potent inhibitor of enkephalinase A to label the protease in rat kidney. The binding of [3H]-acetorphan to kidney membrane determined in vitro with both equilibrium and kinetic methods is saturable and reversible involving a single class of sites with a dissociation constant of 4-5.3 nM. The [3H]-acetorphan binding capacity is identical, Bmax approximately 51 pmoles per mg of proteins, for kidney membranes from Sprague Dawley and Wistar Kyoto rats. In contrast, the enkephalinase A number is decreased in the pathological states studied: 20% for hypertensive rats and 50% for hypercholesterolemic rats. Such pharmacological results provide a great deal of information about the modification appeared in the metabolism of peptidic substrates of enkephalinase A in hypercholesterolemia and hypertension. PMID- 1460603 TI - Characterization of muscarinic receptor subtypes in canine left ventricular membranes. AB - The pharmacological characteristics of muscarinic receptor (mAChR) subtypes in canine left ventricular membranes (LVM) were determined using [3H] quinuclidinyl benzilate ([3H]QNB) and [3H]N-methyl scopolamine ([3H]NMS) as ligands. Binding of [3H]QNB and [3H]NMS was saturable with respect to the radioligand concentrations. Analysis of binding isotherms by Scatchard plot showed that [3H]QNB and [3H]NMS bound to an apparently homogeneous population of mAChRs in LVM, with KD values of 390 +/- 100 and 285 +/- 34 pM and Bmax values of 240 +/- 20 and 133 +/- 9 fmol/mg protein, (n = 6), respectively. The Hill coefficients for [3H]QNB and [3H]NMS binding were 0.95 +/- 0.02 and 0.99 +/- 0.01, respectively. Based on the competitive inhibition of [3H]ligand binding, atropine and NMS as well as the selective M1 antagonist PZ revealed no selectivity for these mAChRs. PZ competed with [3H]QNB or [3H]NMS for a single binding site with a Ki value of 0.23 +/- 0.03 microM and 0.62 +/- 0.10 microM, (n = 6), respectively, which is close to the values of M2 or M3 receptors. The data indicate that the M1 receptor subtype did not exist in canine LVM. Competition of [3H]ligand binding with selective M2 antagonists, AF-DX 116 and methoctramine and the selective M3 antagonists, 4-DAMP and hexahydrosiladifenidol, gave a best fit for a two-binding site model. The inhibition of carbachol-mediated phosphoinositide hydrolysis by PZ, AF-DX 116 and 4-DAMP, generated an affinity profile for this response also dissimilar to that described for the classical cardiac M2 response. Although no other muscarinic receptor mRNA has been detected in this tissue, these data suggest the presence of a second population of muscarinic sites, which may signify an M2 receptor diversity. PMID- 1460604 TI - LPS-induced decrease of specific binding of 3H-dexamethasone to peritoneal macrophages of C57BL/6 mice. AB - The effect of LPS on the specific binding of 3H-dexamethasone to peritoneal macrophages of C57BL/6 mice was studied. Scatchard plot of the specific binding of 3H-dexamethasone to the macrophages indicated that the Kd and Ro of glucocorticoid receptor was approximately 3.0 nM and 5,500 binding sites per cell, respectively. LPS, at the concentration of 10 ug/ml, caused a decrease in the specific binding of 3H-dexamethasone to macrophages after it interacted with the macrophages for different times. Con A, a mitogen for lymphocytes, did not significantly cause a decrease of glucocorticoid receptor in the macrophages at the concentration of 10 ug/ml. Our results indicated that the effect of LPS on the specific binding of 3H-dexamethasone to macrophages was different from the effect of Con A, which might be significant in the interaction of immune system and neuroendocrine system. PMID- 1460605 TI - Modulatory effect of nonesterified fatty acids on structure and binding characteristics of estrogen receptor from MCF-7 human breast cancer cells. AB - Arachidonic, docosahexaenoic and oleic acids were found to produce a dose dependent cytotoxic effect on MCF-7 cells; palmitic and stearic acids were totally ineffective in this regard suggesting that solely unsaturated fatty acids were able to arrest mammary tumor cell growth. Similarly, only former acids were able to decrease the binding capacity and affinity (increase Kd value) of the cells for 3H-E2 in a dose-dependent manner. In the case of arachidonic acid (the reference fatty acid), this decrease was associated with a slight cleavage of the native 67 KDa estrogen receptor (ER) into 50 and 25-30 KDa peptides as demonstrated by sequential labeling of high-salt cell extracts with 3H-tamoxifen aziridine, specific immunoadsorption with H-222 anti-ER monoclonal antibody, SDS PAGE and fluorography. Both, modifications in binding characteristics of ER and cleavage of the native 67 KDa receptor were found to be extremely marked when unsaturated fatty acids were directly added to the high-salt cell extracts. This clear influence on the ER structure was reflected on enzyme immunological assay (EIA) by a reduction of ER immunoreactivity of approximately 50% in presence of arachidonic acid. Our observations are discussed in terms of possible interference of unsaturated fatty acids either through transmembrane modulation of phosphokinases and/or phospholipases implicated in ER mechanism of action, or through an intracellular interaction between ER and these acids acting as second messengers in regulation of cellular functions. PMID- 1460606 TI - Covalent cross-linking of radiolabeled N-formylated hexapeptide to its specific receptor on rat and human neutrophils: evidence for a ligand induced complex formation. AB - The structure of the rat and human neutrophil receptor for N-formylated chemotactic peptides was characterized using 125I-labeled N-formyl-Nle-Leu-Phe Nle-Tyr-Lys hexapeptide as a ligand and an affinity cross-linking technique. 125I hexapeptide bound to purified rat peritoneal neutrophils was time, temperature and pH-dependent. The average receptor number per cell was about 67,000 and dissociation constant (Kd) 0.41 nM. Formyl-MLLP, fMLP, fNLP, were 750%, 15%, 8.6% respectively and Boc-MLP, Boc-NLP, and MLP 0.6% as potent as the hexapeptide in inhibiting the binding of 125I-hexapeptide to rat neutrophils. The same correlation was found between these peptides in their potency to induce chemotaxis. This indicates that the rat neutrophil chemotactic receptor is like human receptor also a highly stereoselective and requires a N-formylated ligand for high affinity binding. Affinity cross-linking of 125I-hexapeptide to rat and human neutrophil chemotactic receptor with glutaraldehyde revealed on SDS-PAGE a 85-kDa and 62-kDa major complex and a 170-kDa and 120-kDa minor complex, respectively. The 120-kDa complex was absent in human neutrophils if the cells were treated with glutaraldehyde prior to cross-linking of 125I-hexapeptide to its receptor. Likewise, the larger complex was absent if neutrophils were exposed to heterologous ligand (C5a) prior to glutaraldehyde treatment and cross-linking of 125I-hexapeptide to its specific receptor. These results demonstrate that the rat neutrophils possess a functional high-affinity receptor for N-formylated chemotactic peptides and that the size of the monomeric receptor is 85-kDa and about 23-kDa larger than that of the human receptor. Upon homologous ligand binding the receptor seems to form a larger complex. PMID- 1460607 TI - Could the fasting plasma glucose assay be used to screen for gestational diabetes? AB - The fasting plasma glucose assay was compared with the one-hour post-glucose test as a screening test for identification of gestational diabetes. Of 4,561 consecutive patients screened with a 50-g glucose test, 968 (21.2%) had results > or = 135 mg/dL; 141 (14.6%, or 3.1% of the total) were found to have diabetes. In the 968 patients, the area under the fasting plasma glucose receiver operating characteristic curve was greater than that under the glucose screening test curve, indicating greater discriminatory value of the former test. Of the 116 patients who had sequential glucose screening tests and fasting plasma glucose assays performed twice during pregnancy, a significant correlation was found for fasting plasma glucose values, but not for glucose screening test values. We conclude that the fasting plasma glucose assay may perform better than the one hour post-glucose test as a screening test for gestational diabetes. Based on these data, a population-based prospective study seems justified. PMID- 1460608 TI - Creatine kinase and its MB isoenzyme in the third trimester and the peripartum period. AB - Forty-nine normal pregnant women were recruited late in the third trimester for serial determinations of creatine kinase (CK) and its MB isoenzyme fraction (CK MB) at four different times: (1) on recruitment between 36 and 40 weeks' gestation, (2) on admission in active labor, (3) immediately after delivery, and (4) on the first postpartum day. In the patients with vaginal delivery (n = 43) total CK was significantly elevated at time 4 compared with times 1, 2 and 3 (P value < .0001). CK-MB fraction was also significantly elevated at time 4 compared with times 1, 2 and 3 (P value < .0001). In 35.7% of the patients at time 4, CK MB was sufficiently elevated to give the laboratory interpretation of "borderline" or "consistent with a myocardial infarction," even though none of the patients had cardiac symptoms or complications. A review of the literature shows that CK-MB is found not only in myocardium but also in uterus and placenta. The implication of this study is that elevations in total CK and CK-MB should be used with caution during the peripartum period to diagnose myocardial ischemia or infarction. PMID- 1460609 TI - Ultrasonic surgical aspirator in cytoreduction of splenic metastases to avoid splenectomy. AB - The Cavitron Ultrasonic Surgical Aspirator (Cavitron) was used to reduce the volume of splenic metastases in seven patients. Six patients had epithelial carcinoma of the ovary, and one had peritoneal mesothelioma. All patients had stage IIIC disease. Initially, six patients had malignant disease > 15 mm in diameter (of any single nodule), and one had disease 6-15 mm in diameter. In order to avoid resection of the spleen, cytoreduction could not be performed by standard means. After using the Cavitron, three patients had no gross residual disease, and four patients had disease 1-5 mm in diameter. No complication resulted from cytoreduction of splenic disease using the Cavitron, and splenectomy was not performed in any case. The Cavitron is invaluable in obtaining minimal residual disease of splenic metastases without performing splenectomy. PMID- 1460610 TI - Laparoscopy using a simplified open technique. A review of 585 cases. AB - Laparoscopy was carried out using a simplified open method on 585 patients. In the group, 173 (29.5%) had undergone a previous laparoscopy or laparotomy, 28 (4.8%) suffered from gross obesity and 1 patient had a large umbilical hernia. Laparoscopy was diagnostic in 216 (37%) patients and operative in 369 (63%). In this series there were no technical failures or major complications; the incidence of minor complications was 2.7%. The above results seem to suggest that open laparoscopy compared to the closed method may offer the advantage of a lack of contraindications secondary to previous surgery, no risk of failure with unintended laparotomy and, possibly, decreased postoperative discomfort. A larger, randomized series to settle the controversy between closed and open laparoscopy regarding the safety differences between the two approaches may result in more widespread use of the open technique. PMID- 1460611 TI - Diagnosis of intrauterine growth retardation as a two-step process with morphometric ultrasound and Doppler umbilical artery velocimetry. AB - Ultrasound and Doppler umbilical artery velocimetry have been used to diagnose the small-for-gestational-age (SGA) fetus. Both techniques are relatively inefficient for this diagnosis. The aim of the present study was to see whether their serial use improved diagnostic accuracy. Forty women with an ultrasound diagnosis of SGA within three weeks of delivery were studied with velocimetry, and the outcome was evaluated. Diagnostic accuracy was improved from 65% by ultrasonography alone to 92% by the addition of an abnormal umbilical artery waveform (P < .02). An abnormal waveform was associated with an adverse outcome in 62%, compared to 14% with normal velocimetry (P < .01). The majority of small fetuses have a normal outcome. The combination of ultrasonography and velocimetry improved diagnostic accuracy and identified those small fetuses truly at risk. PMID- 1460612 TI - Does douching promote ascending infection? AB - Despite the fact that vaginal douching is practiced regularly by approximately 20 million American women, little is known about who douches, why or its associated risks or benefits. Recent studies of douching collectively suggest a possible association with ectopic pregnancy and pelvic inflammatory disease. These findings, however, are difficult to interpret because of the small number of studies, conflicting findings and methodologic weaknesses, reflecting both the early stage of interest and difficulties inherent to studies of intimate behaviors. Further information is needed to differentiate between douching as a causal factor or as an indicator for behaviors that increase the risk of sexually transmitted diseases and their complications. The central issue is whether other risk factors and/or markers for sexually transmitted diseases, which are more common among women who douche, have been reasonably excluded as a source of bias. Few, if any, criteria for establishing a causal link between douching and adverse outcomes are satisfied, but this reflects a paucity of data rather than data that refute such a conclusion. PMID- 1460613 TI - Splenic artery aneurysm rupture in pregnancy with maternal and fetal survival. A case report. AB - A splenic artery aneurysm occurred at 30 weeks, 3 days' gestation. Both the mother and fetus survived. PMID- 1460614 TI - Ultrasound diagnosis of a twin gestation with concordant body stalk anomaly. A case report. AB - Concordant body stalk anomaly in an 18-week twin gestation was diagnosed by ultrasound and confirmed by pathologic examination after elective termination of pregnancy. The ultrasonographic presentation of this rare anomaly and its embryogenesis are discussed. PMID- 1460615 TI - Roseola infantum in pregnancy. A case report. AB - Roseola infantum (exanthem subitum) was first described as a specific syndrome by Zahorsky in 1913. It is a benign disease that occurs almost exclusively in infants and young children (six months to three years of age). We report a case of roseola in a pregnant woman. We were unable to find any prior reports of roseola in pregnancy. The classic presentation of roseola is characterized by high temperatures (103-105 degrees F) that last 3-5 days and resolve by crisis followed by the appearance of a morbilliform rash that lasts a few hours to a few days. The infectious agent is human herpesvirus-6. We recommend the addition of roseola to the differential diagnosis of rashes that occur in pregnancy. The potential danger to the fetus from this virus is unknown. PMID- 1460616 TI - Intraamniotic infection with Candida albicans associated with a retained intrauterine device. A case report. PMID- 1460617 TI - Distribution of the Lyme disease vector, Ixodes dammini (Acari: Ixodidae) and isolation of Borrelia burgdorferi in Ontario, Canada. AB - Ixodes dammini Spielman, Clifford, Piesman & Corwin was confirmed at Long Point, Lake Erie, Ontario, on small mammals and white-tailed deer and by dragging for ticks. Mean intensities of up to 16.2 larvae and 2.1 nymphs were found on Peromyscus leucopus (Rafinesque), with an overall prevalence of infestation up to 92%. Adult I. dammini (101.6 +/- 77.63) (mean +/- SD) were found on 8 white tailed deer, Odocoileus virginianus (Zimmerman). The seasonal pattern of recovery of ticks from hosts and the environment resembled that described elsewhere. I. dammini was not found on 952 small mammals trapped at 25 other localities throughout Ontario, although other ticks (Derma-centor variabilis (Packard), Ixodes angustus Neumann, I. marxi Banks, I. muris Bishopp & Smith) were encountered sporadically. I. dammini is not widespread or common in Ontario other than at Long Point. Borrelia burgdorferi was isolated from 10 of 151 P. leucopus; from larval and nymphal I. dammini; and from nymphal and adult D. variabilis, all from Long Point. B. burgdorferi was not recovered from 116 small mammals from localities other than Long Point. Seropositive P. leucopus (indirect fluorescent antibody test titer > or = 1:20) were common (up to 30% prevalence in July 1988, n = 23) on Long Point. Where I. dammini was not found, the prevalence of seroreactors among Peromyscus was 0 (15 sites), < 12% (5 sites), and 29% (1 site); seroprevalence at 1:20 could not be calculated for a further 4 sites examined in 1987. Antibody to B. burgdorferi was also detected in other small mammals at some sites. Such antibody was interpreted as possibly cross-reacting or caused by direct transmission. PMID- 1460618 TI - Synganglial morphology and neurosecretory centers of adult Amblyomma americanum (L.) (Acari: Ixodidae). AB - Lone star ticks, Amblyomma americanum (L.), were processed by standard histological means for paraffin embedding, sectioning, and staining by the paraldehyde-fuchsin technique. The synganglion is highly condensed around the esophagus and possesses paired optic, cheliceral, palpal, pedal I-IV nerves, and opisthosomal nerves and a single unpaired esophageal nerve. Although optic nerves were observed leading from the eyes to the protocerebrum, distinct optic ganglia were not seen in any of the preparations examined. The paraldehyde-fuchsin technique revealed 14 neurosecretory centers (11 paired, 3 unpaired) within the synganglion, which are described in relation to the underlying neuropilar structure. A previously undescribed internal subesophageal center that consists of a single cell was observed within a cluster of perikarya lying posteriorly adjacent to the esophagus. A three-dimensional reconstruction of the internal neuropilar structure of the synganglion was made, and the included neurosecretory centers were mapped. Comparisons are made to previous work on other ticks, and physiological relationships are considered. PMID- 1460619 TI - Female Aedes aegypti (Diptera: Culicidae) in Thailand rarely feed on sugar. AB - Female Aedes aegypti (L.) of two different body sizes and provided with different diets (20% sucrose, water only, or 20% sucrose + human blood) were marked and released together in a rural Thai village. Recaptured marked and unmarked (wild) adults were tested for fructose by the cold-anthrone reaction. Both released and wild females showed a low frequency of sugar feeding in nature; both small-bodied and large-bodied individuals failed to sugar feed significantly. Marked females released with sugar in their crop utilized this energy source over the following 2-3 d but failed to replenish it. In contrast, about one-third of wild, resting males showed evidence of recent sugar feeding. This indicated that the absence of plant sugar in females was not caused by a shortage of nectar sources in this rural domestic environment. Presumably, the nonutilization of plant sugar as an energy source increases the frequency of blood feeding and, therefore, the vectorial capacity of Ae. aegypti. PMID- 1460620 TI - Differentiation of vector species of phlebotominae (Diptera: Psychodidae) in Kenya by chorionic sculpturing of their eggs. AB - Chorionic sculpturing on eggs of Phlebotomus pedifer Lewis, Mutinga, and Ashford; the closely related Phlebotomus aculeatus Lewis, Minter, and Ashford (= P. elegonensis Ngoka, Madel, and Mutinga); and Phlebotomus martini Parrot was examined and compared by scanning electron microscopy. The eggs of P. pedifer had a general pattern of longitudinal ridges; those of P. aculeatus and P. martini exhibited intraspecific differences. Chorionic patterns of eggs were not reliable to differentiate these species. It is suggested that other methods of differentiation should be used on these species. PMID- 1460621 TI - Detection and identification of mammalian DNA from the gut of museum specimens of ticks. AB - A method for detection and identification of mammalian DNA in the gut of alcohol preserved ticks has been developed. Successful amplification and sequencing of host cytochrome b is reported from ticks preserved in 70% alcohol for more than 40 yr. The method described shows promise for determination of unknown tick hosts. PMID- 1460622 TI - Distribution of Ixodes dammini (Acari: Ixodidae) in residential lawns on Prudence Island, Rhode Island. AB - The distribution of nymphal Ixodes dammini Spielman, Clifford, Piesman & Corwin in residential lawns was assessed by flagging on Prudence Island, RI. The number of ticks per sample was five times greater in lawns adjacent to woods than in lawns adjacent to other lawns. Relative tick abundance was negatively correlated with distance from the woods, but the decline was gradual. Spirochete prevalence in ticks did not differ among lawn types or at different distances from the woods. Therefore, barriers that keep people away from the wood edge probably lower the risk of acquiring Lyme disease, but there is still a risk. Even with physical barriers at lawn-wood edges, personal precautions to prevent tick bites should be followed. PMID- 1460623 TI - Similar reproductive status and body size of horse flies (Diptera: Tabanidae) attracted to carbon dioxide-baited canopy traps and a Jersey bullock. AB - The reproductive status and body size of four Tabanus species collected from canopy traps baited with carbon dioxide and from a Jersey bullock were compared. Parity rates, sperm prevalence, stage of follicular development in terminal follicles of parous females, prevalence of females retaining eggs, average number of eggs retained in parous flies, and the body size of parous females did not differ significantly between sampling methods. Based on the presence of nulliparous host-seeking flies, Tabanus pallidescens Philip and T. wilsoni Pechuman can be added to the list of tabanids found to be anautogenous. PMID- 1460624 TI - Occurrence of Ixodes pacificus (Parasitiformes: Ixodidae) in Arizona. AB - Adults and immatures of Ixodes pacificus Cooley & Kohls were collected by flagging vegetation and from lizards during a 3-mo period in the Hualapai Mountain Park, Mohave County, AZ, in 1991. Collections were made at altitudes > or = 2,134 m. Two of 48 gut-salivary gland extracts of adult ticks were positive by IFA using a monoclonal antibody (H5332) specific to Borrelia burgdorferi. These are the first records of I. pacificus and of spirochetes tentatively identified as B. burgdorferi in Arizona. PMID- 1460625 TI - Isolation of the Lyme disease spirochete, Borrelia burgdorferi, from Ixodes dammini (Acari: Ixodidae) collected on Prince Edward Island, Canada. AB - Studies were undertaken to monitor for the presence of Borrelia burgdorferi, the etiologic agent of Lyme disease, on Prince Edward Island, Canada. Gut contents were removed for culturing from seven engorged ticks collected in 1991-1992 including five Ixodes dammini (Spielman, Clifford, Piesman & Corwin) and two I. scapularis (Say) removed from a dog that had recently traveled to the southern United States. B. burgdorferi was recovered from one I. dammini that had been removed from a cat in Charlottetown in October 1991. The cat had not traveled off the island. Immunofluorescent antibody (IFA) studies on sera from 75 dogs, 7 cats, and 8 white-tailed deer (Odocoileus virginianus) collected on Prince Edward Island between 1989 and 1992 revealed one reactor with an IFA titer > or = 1:256. The reactor was a dog with a history of travel to the United States. This report documents the first isolate of B. burgdorferi in Atlantic Canada, possibly because of the introduction of I. dammini on migratory birds. Serological studies do not indicate widespread occurrence of B. burgdorferi on Prince Edward Island. PMID- 1460626 TI - Clothing impregnations of dibutylphthalate and permethrin as protectants against a chigger mite, Eutrombicula hirsti (Acari: Trombiculidae). AB - A field study to compare the effects of wearing military uniforms treated with permethrin or dibutylphthalate as protection against the chigger Eutrombicula hirsti (Sambon) was conducted in northern Queensland, Australia, during November 1990. Volunteers who wore treated uniforms received significantly fewer chigger attachments than individuals who wore untreated uniforms. Australian military uniforms treated with dibutylphthalate provided a 97.6% increase in protection, whereas uniforms treated with 0.058-0.101 mg/cm2 permethrin provided 96.4% protection. U.S. Army uniforms treated with 0.125 mg/cm2 permethrin provided 83.2% protection. The differences between the clothing treatments were not significant. The results show that wearing clothing impregnated with either compound is an effective method for personal protection against E. hirsti. PMID- 1460627 TI - Failure of dengue viruses to replicate in Culex quinquefasciatus (Diptera: Culicidae). AB - Culex quinquefasciatus (Say) and Aedes aegypti (L.) were parenterally infected with dengue viruses and virus replication was monitored at intervals after infection in each species. Dengue viruses replicated rapidly in Ae. aegypti, reaching a peak titer of 10(6)-10(7) mosquito infectious dose 50 (MID50) per mosquito. In Cx. quinquefasciatus, however, dengue virus replication did not occur. We conclude that this mosquito species is refractory to infection with dengue viruses and, therefore, does not serve as a vector in nature. PMID- 1460628 TI - Studies on the ecology of Lyme disease in a deer forest in County Galway, Ireland. AB - The abundance of the tick Ixodes ricinus (L.) and the infection rate of ticks with Borrelia burgdorferi (Johnson et al.) were compared on either side of a deer fence in a forest park in County Galway, Ireland, in an attempt to elucidate the role of fallow deer, Dama dama, and woodmice, Apodemus sylvaticus, in determining the population density of I. ricinus and the transmission of B. burgdorferi. The results showed that tick numbers were much higher on the deer side of the fence, although the density of mice was similar on both sides. This suggests that, in the absence of other obvious factors, deer rather than mice are responsible for tick abundance in this habitat. Tick infection rates, determined by immunofluorescence, were consistently higher outside the deer fence than inside it. It is suggested, therefore, that mice rather than deer may be the important reservoir hosts of B. burgdorferi in this habitat and that deer, by feeding many larvae, probably contribute large numbers of uninfected ticks to the population. If this is the case, there will not be a direct relationship between deer abundance and tick infection rates. This has important implications for risk assessment. PMID- 1460629 TI - Relationship between female Anopheles dirus (Diptera: Culicidae) body size and parity in a biting population. AB - Wing length of host-seeking Anopheles dirus Peyton & Harrison was measured in Tha Mai District, Chanthaburi Province, Thailand. Overall, wing length of nulliparous females (mean = 3.035 mm) was not significantly smaller than that of parous females (mean = 3.039 mm). Wing length was correlated with rainfall and minimum air temperature; females tended to be smaller in the rainy season and larger in the cool and early dry seasons, often in association with a high parity rate. Malaria transmission potential based on daily survivorship was estimated to be highest during the cool and early dry seasons, and during the first half of the rainy season. PMID- 1460630 TI - Xenopsylla bantorum is an east African subspecies of X. cheopis (Siphonaptera: Pulicidae). AB - The geographic distribution, host association, and male genital morphology of Xenopsylla bantorum Jordan were examined and compared with the Nilotic and Oriental "strains" of Xenopsylla cheopis (Rothschild). The more acute shape of the ninth sternite separates X. bantorum from all types of X. cheopis; however, the length of the first process of the male's clasper and the number of setae on this process are significantly different among all three groups; the Nilotic strain of X. cheopis is intermediate to the others. Specimens collected from both wild and commensal rodents in Nakuru, Kenya, were all X. bantorum, suggesting that X. cheopis present early in the century that resulted from introductions on Rattus rattus had been absorbed by the native X. bantorum population. These factors and a review of opinions by others concerning the status of X. bantorum demonstrate that this flea is not specifically distinct from X. cheopis. The trinomial X. cheopis bantorum is erected. Furthermore, the Nilotic and Oriental "strains" of X. cheopis are distinguishable morphologically solely by the length of the male's first process. PMID- 1460631 TI - Host immunity to mosquitoes: effect of antimosquito antibodies on Anopheles tessellatus and Culex quinquefasciatus (Diptera: Culicidae). AB - Rabbit antibodies to antigens derived from the tissues of sugar-fed Anopheles tessellatus Theobald were fed to An. tessellatus and Culex quinquefasciatus Say in blood meals. These antibodies tended to reduce the number of eggs produced by An. tessellatus, but had no effect on the fecundity of Cx. quinquefasciatus. Ingestion of the rabbit antibodies did not detectably affect the mortality of An. tessellatus but increased the mortality of Cx. quinquefasciatus. The results provide preliminary evidence for the potential of antimosquito antibodies to disrupt the physiology of mosquito vectors and indicate the need for further studies with high-titer, monospecific antibodies against the relevant target antigens. PMID- 1460632 TI - Random amplified polymorphic DNA of mosquito species and populations (Diptera: Culicidae): techniques, statistical analysis, and applications. AB - A polymerase chain reaction (PCR)-based method is described for the identification and differentiation of mosquito species and populations. The method, described first by Williams et al. (1990), employs single 10 base-long primers of arbitrary DNA sequence and results in the amplification of random segments of DNA known as random amplified polymorphic DNA (RAPD). We wished to determine if RAPD of mosquito DNA could be used for the differentiation of species and populations, identification of unknown specimens, and the reconstruction of phylogeny. RAPD of mosquito DNA results in the amplification of a series of DNA fragments of varying length. Most amplified fragments are unique to an individual; however, our data indicated that in each of the five species of Aedes examined, some fragments are species-specific and are present in all individuals of that species. This enabled us to derive a diagnostic profile for each of the five species. A nearest-neighbor analysis of all the amplified DNA fragments discriminated among species on a multivariate basis. Several individuals of Aedes albopictus (Skuse), included in the analysis as "unknowns," were correctly identified as belonging to Ae. albopictus. UPGMA clustering of presence-absence data enabled the separation of different Aedes species as well as different populations of Ae. albopictus. The entomological applications of RAPD include the construction of diagnostic profiles for species identification and differentiation among conspecific populations. PMID- 1460634 TI - Preparation and examination of flea larvae (Siphonaptera) by light and electron microscopy. AB - Techniques are described for making permanent slide-mounted specimens. Larvae were thoroughly macerated in KOH to remove soft internal tissue, yielding specimens with enhanced transparency and allowing examination of most of the exoskeleton in a single larva. Fatty material was removed in acetone to eliminate confusion of fat globules with sensilla in the cuticle. The more sclerotized exoskeletal elements, such as integumentary scales and the body sclerites together with their setae and sensilla, were highlighted by staining with carbol fuchsin. Resolution of numbers and arrangement of setae, especially those on the dorsum of the head capsule, in the anal comb, and on the anal mounds, was greatly facilitated by mounting larvae in dorsal orientation. Clearer views of the antennae and mouthparts were obtained, in orientations seldom achieved in whole mounts, by dissecting the head capsule. Discrimination of many taxonomically valuable features was enhanced by the use of phase-contrast microscopy. Interpretation of structures noted in light microscopy was complemented using scanning electron microscopy. The latter allowed differentiation between surface and internal cuticular structures. PMID- 1460633 TI - Reproductive activity of Synosternus cleopatrae (Siphonaptera: Pulicidae) in relation to host factors. AB - Reproductive activity of Synosternus cleopatrae (Rothschild) infesting Gerbillus andersoni allenbyi Thomas was studied in a natural setting in Israel. Rodents were trapped and measured (weight and length), their sex was identified, and their reproductive status estimated. Their ectoparasites were removed, and fleas were dissected and their oocytes measured. Two indices of flea reproductive activity were analyzed: "reproductive status," which distinguished between gravid and nongravid females, and "reproductive intensity," which was estimated as the sum over the two largest oocytes of the products of oocyte length multiplied by oocyte width. Both indices showed that no reproduction took place between November and January, but reproduction was relatively stable during the rest of the year. Although flea reproductive activity differed significantly among individual hosts, only a small fraction of gerbils (10-15%) carried a significantly different proportion of reproductive fleas than their monthly sample proportion (based on all fleas regardless of hosts). All these hosts carried a lower proportion of reproductive fleas than their monthly sample proportion. The host's sex, but not reproductive status or age, had a significant effect on flea reproduction, expressed as a higher reproductive activity on male gerbils. Infestation burden expressed as ectoparasite counts was included in the statistical analysis. Only lice, Polyplax gerbilli Ferris, but not S. cleopatrae, Stenoponia tripectinata (Tiraboschi), and a total of five mesostigmatid Acari had a significantly negative association with S. cleopatrae reproductive activity. These relationships between S. cleopatrae reproductive activity and the host infestation burden do not support the hypothesis of modulation of S. cleopatrae reproduction by the infestation burden. However, differences in the reproductive activity of ectoparasites between their hosts may play a major role to generate the parasite clumped distribution. Thus, gerbil males probably carry more fleas than gerbil females because of the higher reproductive activity of S. cleopatrae on gerbil males. PMID- 1460635 TI - Food ingestion and digestive enzymes in larval Aedes aegypti and Ae. albopictus (Diptera: Culicidae). AB - Frequency of the labral brush movements of first, second, and fourth instars of Aedes aegypti (L.) and Aedes albopictus (Skuse) was studied comparatively in the laboratory. A frequency of 197 strokes per min for the first and second instars was observed in the former species compared to 118 strokes per min in the latter species. A faster ingestion rate of algal cells also was observed in first and second instars of Ae. aegypti (mean 57.5 cells per s) compared with first and second instars of Ae. albopictus (mean 22.4 cells per s). The digestive enzymes chymotrypsin (EC 3.4.21.1) and trypsin (EC 3.4.21.4) were more active in the peritrophic membrane (including food contents) than in the midgut epithelium of both species. Chymotrypsin activity in 11-d-old third and fourth instars of Ae. albopictus was 28 times higher than in the corresponding stadia of Ae. aegypti, indicating that the former species may have a superior enzymatic process for digesting food proteins. PMID- 1460636 TI - The genus Parasecia (Acari: Trombiculidae), with the description of a new species from Mexico. AB - The genus Parasecia Loomis, 1966, is redefined, and Parasecia bulbocalcar Goff is described as new from specimens collected off a Yellow-shouldered Bat, Sturnia ludovici Anthony, taken in Morelos, Mexico. A key to the 15 species of Parasecia is provided. PMID- 1460637 TI - Effects of Ascogregarina barretti (Eugregarinida: Lecudinidae) infection on Aedes triseriatus (Diptera: Culicidae) in Illinois. AB - Ascogregarina barretti (Vavra), a gregarine protozoan parasite, infected 23.6 and 5.0% of Aedes triseriatus (Say) adults that emerged from pupae collected from an east-central Illinois tire dump in 1990 and 1991, respectively. Infection significantly reduced the wing length of males and females in both years, but its effect was greatest in 1991. Females were approximately 1.7 times as likely to be infected as males. Infected pupae were 3.53 and 2.76 times more likely to die than uninfected pupae in 1990 and 1991, respectively. Wing length also was affected by location within the tire dump and by tire water volume. We conclude that the A. barretti infection was deleterious to Ae. triseriatus and that the effects of this pathogen may be moderated by environmental factors. PMID- 1460638 TI - Laboratory evaluation of Acanthocyclops vernalis and Diacyclops bicuspidatus thomasi (Copepoda: Cyclopidae) as predators of Aedes canadensis and Ae. stimulans (Diptera: Culicidae). AB - Predatory effectiveness of two vernal-pool copepods, Acanthocyclops vernalis (Fischer) and Diacyclops bicuspidatus thomasi (Forbes), was assessed against cohabiting larvae of Aedes canadensis (Theobold) and Aedes stimulans (Walker) in laboratory bioassays. D. b. thomasi did not exhibit predatory behavior toward first instars, even when both organisms were confined in 35-mm wells for 7 d and alternative food sources were not available. A. vernalis did feed on early instars, but its effectiveness was significantly influenced by the presence of alternate food, the size of the container, and the size and age of the larval prey. Results strongly suggest that in a comparatively unrestricted natural vernal-pool habitat where an abundance of other food sources are available, neither copepod species plays a major role in reducing larval mosquito populations. PMID- 1460640 TI - Variation in the efficiency of vertical transmission of dengue-1 virus by strains of Aedes albopictus (Diptera: Culicidae). AB - Five geographical strains of Aedes albopictus (Skuse) were compared for their ability to transmit vertically a dengue-1 isolate from Jamaica. The OAHU strain of Ae. albopictus and a strain of Aedes aegypti (L.) from the United States were included as controls. The offspring of orally infected females were assayed individually for vertical infection. Vertical transmission rates among strains ranged from 11 to 41%, and filial infection rates of strains ranged from 0.5 to 2.9%. Filial infection rates of individual positive families within strains ranged from 1.4 to 17.4%. These rates were higher than those previously recorded for Ae. albopictus. The observed differences in rates of vertical transmission among the strains were not statistically significant, because 95% of the measured variation was attributed to families within strains. The most significant source of variation in vertical transmission of dengue-1 by Ae. albopictus was at the individual level. PMID- 1460639 TI - Detection of Borrelia burgdorferi in laboratory-reared Ixodes dammini (Acari: Ixodidae) fed on experimentally inoculated white-tailed deer. AB - Larvae and nymphs of Ixodes dammini Spielman, Piesman, Clifford & Corwin from a laboratory colony were fed on two white-tailed deer, Odocoileus virginianus (Zimmerman) inoculated with either the SH2-82 or JD-1 strains of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner. Ticks were exposed to one deer 43 and 69 d after inoculation of the spirochete and to a second deer 35 and 61 d after inoculation. Polymerase chain reaction assays amplified the 158 bp OspA DNA target sequence in 11.1% (n = 9) of fed larvae and 3.3% (n = 30) of nymphs from the deer inoculated with the SH2-82 strain, and 22.7% (n = 22) of larvae and 0% (n = 21) of nymphs from a second deer inoculated with the JD-1 strain of B. burgdorferi. One of three females derived from nymphs fed on one of the inoculated deer showed presence of B. burgdorferi DNA, but none of four males was positive. Experimentally inoculated deer can serve as a source of at least two geographic strains of B. burgdorferi to I. dammini larvae and nymphs for at least several weeks. PMID- 1460641 TI - African swine fever virus infection in the soft tick, Ornithodoros (Alectorobius) puertoricensis (Acari: Argasidae). AB - In total, 1,186 second instar Ornithodoros (Alectorobius) puertoricensis Fox second instars were fed on a pig when it had a viremia of 10(5.2) hemadsorption units (HAd50/ml) and 420 second-instar O. puertoricensis were fed on an uninfected pig. Subsequent blood meals for ticks in both groups were from uninfected pigs. The effects of African swine fever virus (ASFV) infection on O. puertoricensis populations were evaluated for the following parameters: mortality; mean time to death; percentage molted per instar; percentage molted to male, female, or subsequent instar; effects on duration of premolt period; and the number of blood meals per instar. The cumulative virus-induced mortality rate for all immature stages (second to fifth instar) of O. puertoricensis that had been fed as second instars on a pig infected with ASFV was 43.2%. In contrast, 23.1% mortality was observed among ticks fed on uninfected pigs. The mortality rate among third instars that fed on the viremic pig was 55.3% versus 4.8% among nymphs fed on normal pigs. One-third to more than one-half of all third, fourth, and fifth instars required at least two blood meals to molt. Mean premolt periods for second, third, fourth, fifth, and sixth instars fed on uninfected pigs were approximately 12, 15, 32, 22, and 14 d, respectively. Mean weights for unfed second to fifth instars, males, and females were: 0.6, 1.0, 1.5, 1.7, 1.5, and 3.1 mg per tick, respectively. PMID- 1460642 TI - Could Aedes albopictus (Diptera: Culicidae) become established in California tree holes? AB - The ability of temperate zone-adapted Aedes albopictus (Skuse) to survive and complete development in California tree holes was evaluated in laboratory experiments that assessed development under simulated wet-season conditions, larval competition with Aedes sierrensis at different food levels, temporal survivorship of eggs stored under different humidities and temperatures, and suitability of larvae as hosts for the indigenous parasite Lambornella clarki. At all resource levels, Ae. albopictus completed development at temperatures similar to those in natural tree hole water in spring and early summer (> or = 16 degrees C), but not those during the rainy winter months (4-11 degrees C). In competition studies at 21 degrees C, the population performance (i.e., survivorship, pupation time, and adult size) of Ae. albopictus at all resource levels was as good or better when larvae developed with Ae. sierrensis compared with when reared with only conspecifics. Egg survivorship declined with increased storage time, increased temperature, and decreased humidity; > 55% of eggs hatched following 24 wk storage at 11 degrees C with relative humidities > 78%. In host suitability tests, parasitic theronts of L. clarki consistently attacked Ae. albopictus larvae at rates significantly lower than Ae. sierrensis. L. clarki that successfully invaded Ae. albopictus larvae failed to multiply and kill their hosts; thus, Ae. albopictus is not a suitable host for L. clarki. The protracted drying of most tree holes and low water temperatures during the rainy season will hinder but not preclude establishment of Ae. albopictus in California. PMID- 1460643 TI - Caring, men and women, nurses and doctors, and health care ethics. PMID- 1460644 TI - HIV infection and AIDS: the ethics of medical confidentiality. AB - An Institute of Medical Ethics working party argues that an ethically desirable relationship of mutual empowerment between patient and clinician is more likely to be achieved if patients understand the ground rules of medical confidentiality. It identifies and illustrates ambiguities in the General Medical Council's guidance on AIDS and confidentiality, and relates this to the practice of different doctors and specialties. Matters might be clarified, it suggests, by identifying moral factors which tend to recur in medical decisions about maintaining or breaching confidentiality. The working party argues that two such factors are particularly important: the patient's need to exercise informed choice and the doctor's primary responsibility to his or her own patients. PMID- 1460645 TI - On visibility: AIDS, deception by patients, and the responsibility of the doctor. AB - Contrary to the usual discussion of lying or deceiving in medical ethics literature where the lying or deceiving is done by the doctor or surgeon, this paper deals with lying or deceiving on the part of the patient. Three cases involving HIV-infected male homosexual or bisexual persons are presented. In each case the patient deceives or wants the doctor to deceive a third party on his behalf. Are such deceptions or lies expressions of compassion? Are they in the patient's best interests? Do they compromise the doctor's integrity? It is submitted that societal attitudes towards male homosexual acts were internalised by the men described in these cases. Thus, a dichotomy was created between the private life and the public image. Fear of condemnation by the doctor or others restricted communication towards the goal of the maintenance of the patient's health. The lack of trust which inhibits truth-telling results in mutual and progressive isolation and impedes the provision of optimal care. PMID- 1460646 TI - Ethical dilemmas in malaria drug and vaccine trials: a bioethical perspective. AB - Malaria is a disease of developing countries whose local health services do not have the time, resources or personnel to mount studies of drugs or vaccines without the collaboration and technology of western investigators. This investigative collaboration requires a unique bridging of cultural differences with respect to human investigation. The following debate, sponsored by The Institute of Medicine and The American Society of Tropical Medicine and Hygiene, raises questions concerning the conduct of trans-cultural clinical malaria research. Specific questions are raised about the difficulties of informed consent in different cultural settings and whether there is any role for community involvement. Discussants debate whether drug and vaccine trials not approved in an industrialised country are ever defensible if performed in a third world setting. Potential conflicting priorities between investigators are discussed and ideas regarding conflict resolution are offered. PMID- 1460647 TI - Epidemiology and moral philosophy. AB - To an increasing extent ethical controversies affect and sometimes obstruct public health work and epidemiological research. In order to improve communication between the concerned parties a model for identification and analysis of ethical conflicts in individual-based research has been worked out in co-operation between epidemiologists and moral philosophers. The model has two dimensions. One dimension specifies relevant ethical principles (as beneficence, non-maleficence, autonomy and justice). The other dimension specifies the groups of persons involved in the conflict under consideration (for example: the study population, individuals who may benefit from the results, the researchers and their personnel, the community at large). The model has been applied to the problem of legitimacy of case-register research and to problems in psychiatric health services research as well as epidemiological research. PMID- 1460648 TI - Should public health respect autonomy? AB - This paper suggests that public health, due to its community orientation, may be ignoring certain ethical principles--namely the rights of individuals and communities to self-determination. The expectation of individual rights as a member of a community is reviewed and the additional right of a community for self-determination is proposed. The influences on ethical evaluations by the legal and economic environments are suggested, using US examples. The conclusion argues that as the focus of health-care delivery changes, it will become more important to consider these questions of group ethics. PMID- 1460649 TI - Gilligan: a voice for nursing? AB - The current reform of nursing education is resulting in major changes in the curricula of colleges of nursing. For the first time, ethical and moral issues are being seen as an important theme underpinning the entire course. The moral theorist with whose work most nurse teachers are acquainted is Kohlberg. In this paper, it is suggested that his work, and the conventions of morality which he exemplifies, may not be the most appropriate from which to address the moral issues facing the nurse. The author suggests that the work of Carol Gilligan of Harvard university is of great significance, not only for nurses involved in the teaching of ethics, but for all nurses. Gilligan's emphasis on caring and relationships accords with the common experience of the nurse, and echoes the current revival of interest within nursing in examining, and valuing, the phenomenon of caring. PMID- 1460650 TI - Let's keep metaphysics out of medical ethics: a critique of Poplawski and Gillett. AB - I argue that the concept of 'longitudinal form', which Poplawski and Gillett have introduced into ethical discussions about embryos and gametes, involves too many metaphysical subtleties to be a useful aid to making moral decisions. I conclude by suggesting a criterion for relevance in medical ethics. PMID- 1460652 TI - HIV-positive surgeon. PMID- 1460651 TI - Response to Pross. PMID- 1460653 TI - Nomenclature of Salmonella. PMID- 1460654 TI - Serum antibodies to verotoxin-producing Escherichia coli (VTEC) strains in patients with haemolytic uraemic syndrome. AB - Serological evidence of infection with verotoxin-producing Escherichia coli (VTEC) was sought in 28 patients suffering from haemolytic uraemic syndrome (HUS) and 25 age- and sex-matched controls. ELISA was used to detect anti lipopolysaccharide (LPS) antibodies to E. coli strains O157, O111, O26 and NCTC 10418, a non-VTEC strain, and Shigella dysenteriae O1. Sera from 19 of the HUS patients but from none of the 25 controls had significant antibody levels to the verotoxin-producing bacteria. Sera from 13 patients reacted with only one LPS of the four verotoxin-producing bacteria; sera from six reacted with more than one LPS antigen but not with LPS of E. coli NCTC 10418. Paired sera taken 2-3 weeks apart were obtained from 20 HUS patients; 14 of these had high levels of antibody in the acute phase sample. Analysis of antibody levels in the convalescent sera showed that one patient had an increase, one was unchanged and 12 patients had a decrease in antibody to the verotoxin-producing bacteria. PMID- 1460655 TI - Comparison of cell-wall teichoic acid with high-molecular-weight extracellular slime material from Staphylococcus epidermidis. AB - Extracellular high-mol.-wt material was separated from liquid cultures of Staphylococcus epidermidis. This material contained protein c. 20% w/w and polysaccharide c. 80% w/w. The polysaccharide was isolated by gel and ion exchange chromatography and contained glycerol phosphate, glucose, N acetylglucosamine, and D-alanine. Cell-wall teichoic acid was isolated from strain RP-62A and had a similar composition. PMID- 1460656 TI - Immunological response to a Staphylococcus aureus fibronectin-binding protein. AB - A protein (gal-FnBP), constructed by fusion of the genes encoding beta galactosidase of Escherichia coli and the binding domains of fibronectin-binding protein (FnBP) of Staphylococcus aureus was used. FnBP is a surface protein responsible for attachment of bacteria to extracellular matrix of various host tissues. Gal-FnBP is more stable and can be produced in larger quantities than native FnBP. The binding specificity of this fusion protein was established in a Western blot analysis. Treatment of gal-FnBP with formalin inactivated the binding capacity of the protein but immunogenicity was retained. Immunisation of mice with formalin-treated gal-FnBP resulted in high antibody titres against the fibronectin-binding part of this fusion protein. These antibodies were measured by their ability to block the specific binding of fibronectin to gal-FnBP in a blocking assay. Sera raised against formalin-treated gal-FnBP and non-treated gal FnBP blocked this binding to 40 and 25% respectively, thereby indicating the usefulness of gal-FnBP as a vaccine component. PMID- 1460657 TI - Protection from Shigella sonnei infection by immunisation of rabbits with Plesiomonas shigelloides (SVC 01). AB - Plesiomonas shigelloides, an organism commonly found in water, is only rarely associated with diarrhoea in man. P. shigelloides serotype O:17 (SVC O1), which is antigenically similar to Shigella sonnei, was found to be neither virulent nor toxic for rabbits. Rabbits immunised by feeding with P. shigelloides (SVC O1) were completely protected against an oral challenge with 10(10) cells of S. sonnei but non-immunised rabbits were not. P. shigelloides (SVC O1) may be a useful vaccine strain for shigellosis. PMID- 1460658 TI - Character and origin of vacuoles induced in mammalian cells by the cytotoxin of Helicobacter pylori. AB - Cytotoxic activity of culture supernates of Helicobacter pylori is manifested by vacuolation of mammalian cells in vitro. The formation and maturation of toxin induced vacuoles in HeLa cells has been studied to examine the possibility that they are autophagosomal in nature. Observation by light microscopy revealed that vacuoles originate in a perinuclear position, increasing in number and size until cell degeneration and lysis occur after 48 h. Ultrastructural study of mature vacuoles indicated the presence of a bounding membrane with contents consisting of degenerate cytoplasmic components and acid phosphatase activity. Confocal fluorescence imaging demonstrated acridine orange accumulation in the vacuoles of toxin-treated cells, indicating an acidic intravacuolar pH. These features are characteristic of autophagosomes. In addition, the size of vacuoles in living, acridine orange-stained cells tended to be inversely proportional to fluorescence intensity. Fluid phase endocytic markers were observed only rarely within nascent vacuoles. Over the succeeding 24 h, labelling of most vacuoles with these dyes was observed. This, along with the observation of intravacuolar acid phosphatase activity, provides evidence that vacuoles communicate at some point during their development with endocytically derived compartments. These observations provide direct evidence for an autophagic origin of these structures. PMID- 1460659 TI - The significance of free and immune-complexed hydatid-specific antigen(s) as an immunodiagnostic tool for human hydatidosis. AB - Micro-enzyme-linked immunosorbent assay (Micro-ELISA) systems were developed and evaluated for the detection of circulating (free or immune-complexed) hydatid antigens in the sera of patients with hydatidosis, by employing monospecific antibodies to hydatid-specific antigens of 8-kDa and 116-kDa. Fifteen (75%) of 20 sera from patients with hydatidosis had both 8-kDa and 116-kDa antigens freely circulating in their sera while three and two samples, respectively, had only 8 kDa or 116-kDa antigen. All the surgically confirmed cases of hydatidosis had detectable levels of both 8-kDa and 116-kDa circulating immune complexes in glycine HCl-treated sera. However, none of the sera from control subjects (patients with cysticercosis, ascariasis, ancylostomiasis, hymenolepiasis, amoebic liver abscess or viral hepatitis) had any detectable level of either type of circulating specific antigen. These results suggest that the demonstration of either 8- or 116-kDa antigen(s) in free or immune-complex form could confirm the diagnosis of hydatidosis. PMID- 1460660 TI - Evaluation of a recombinant antigen ELISA for the diagnosis of acute toxoplasmosis and comparison with traditional antigen ELISAs. AB - An evaluation of five ELISA methods for the diagnosis of acute toxoplasmosis was undertaken by comparing a laboratory-produced ELISA employing two recombinant Toxoplasma gondii polypeptides as antigen with a laboratory-produced ELISA and three commercially available ELISAs employing traditional parasite antigen preparations derived from whole tachyzoites. With a panel of 75 sera from patients who showed either serological and clinical evidence of acute toxoplasmosis, or of diseases caused by other infectious agents, or from patients who showed no evidence of infectious disease, the ELISAs gave overall positive predictive values of 81.6-100%, negative predictive values of 87.8-100%, sensitivities of 81.3-100%, and specificities of 83.7-100%. No two ELISAs gave identical results with all sera tested. In total, the ELISA based on the two recombinant T. gondii polypeptides appeared to be the most specific ELISA in this comparison, showing positive predictive values and specificities of 100% for all groups of patients tested. The overall negative predictive value for this ELISA was 87.8% and the sensitivity was 81.3%. Therefore, the ELISA based on recombinant antigen appears to be a promising advance in the serological diagnosis of acute toxoplasmosis. PMID- 1460661 TI - The clinical comparison of Oxoid Signal with Bactec blood culture systems for the detection of streptococcal and anaerobic bacteraemias. AB - Blood cultures were taken from 47 patients 1-2 min after dental extraction. These samples were tested by the radiometric Bactec 460 and Oxoid Signal systems for the detection of streptococcal and anaerobic bacteraemias. Streptococci were isolated from 19 (40%) patients and anaerobes from 15 (32%). In this study the Oxoid Signal system was significantly better for isolating oral anaerobes than the Bactec system; five isolates were obtained with the Bactec system and 14 with the Signal system. There was no significant difference in the isolation of streptococci between these two systems (Bactec 14, Oxoid Signal 10). The contamination rate was 4.1% for Bactec and 7.5% for the Oxoid Signal system. PMID- 1460662 TI - Identification of surface-exposed Yersinia pestis proteins by radio-iodination and biotinylation. AB - When whole cells (stationary phase) of Yersinia pestis strain EV76 were radiolabelled with Iodogen and 131I, 16 major and 10 minor surface-exposed outer membrane proteins (OMPs) were identified. Labelling with N-hydroxysuccinimidyl 6 biotinylamino-hexanoate (biotin X-NHS) resulted in a complex protein profile detectable after blotting and developing with peroxidase-conjugated avidin. Y. pestis cell fractionation revealed that biotin X-NHS labelled not only OMPs but also proteins of inner cell compartments. Therefore, radiolabelling was the more reliable technique for identifying the OMPs of Y. pestis. PMID- 1460663 TI - Acute urinary retention due to a free-standing broad ligament leiomyoma. AB - A 38-year-old woman who had used oral contraceptives continuously since age 22 presented with acute urinary retention. Physical examination revealed a bladder outlet obstruction due to a large paravaginal/broad ligament mass. Magnetic resonance imaging (MRI) demonstrated that the mass was separate from the uterus which was confirmed at surgery when an isolated free-standing leiomyoma was removed. PMID- 1460665 TI - Cells yield secrets of growth and death. PMID- 1460664 TI - Evaluation of mammographic stellate lesions. AB - Breast masses can be classified into circumscribed masses and stellate masses. Stellate masses are more difficult to detect but are easier to analyze. Good technique, proper processing, proper viewing conditions, and critical comparison of right vs. left and current vs. old can aid in the detection of stellate masses. Once detected, analysis is straightforward. Most will be scirrhous carcinomas. A few will be radial scars, traumatic fat necrosis, or rare benign lesions. Additional signs such as architectural distortion and microcalcifications can be very important. Additional views, including spot compression films, may be decisive. Not all stellate lesions are malignant, but most will require biopsy. Traumatic fat necrosis may be differentiated on the basis of history or radiographic appearance and does not need intervention. Lesions suspicious for carcinoma and radial scars should be excised and examined histologically. PMID- 1460666 TI - European medical oncologists debate benefit of intensive chemotherapy regimens. PMID- 1460667 TI - Researchers gain insight into cell cycle delay. PMID- 1460668 TI - New data suggest fewer mammograms for younger, older women. PMID- 1460669 TI - Razors and refrigerators and reindeer--oh my! PMID- 1460670 TI - Herbicides and cancer. AB - Herbicides are a heterogeneous class of chemicals used in agriculture, forestry, and urban settings to kill weeds, shrubs, and broad-leaved trees. The role of herbicides in the etiology of cancer is controversial. Potential studies for review were identified through a MEDLINE search and from a check of references in related review articles. This review of the literature shows reasonable evidence suggesting that occupational exposure to phenoxy herbicides results in increased risk of developing non-Hodgkin's lymphoma. Several studies have noted large increases in risk of soft-tissue sarcomas with phenoxy herbicide exposure. In contrast, others have failed to observe increased risks, and evidence of an exposure-risk relationship is lacking. Although there have been too few appropriate studies for adequate assessment of risk of cancer at other sites, some findings have linked herbicide exposure with cancers of the colon, lung, nose, prostate, and ovary as well as to leukemia and multiple myeloma. Future studies must better identify and quantify the nature of herbicide exposures. In the interim, it seems only prudent to monitor and promote safety practices among persons occupationally exposed to phenoxy herbicides, particularly farmers and professional sprayers. PMID- 1460671 TI - Natural killer (NK) cell lytic dysfunction and putative NK cell receptor expression abnormality in members of a family with chromosome 3p-linked von Hippel-Lindau disease. AB - BACKGROUND. Using antibodies to a putative natural killer (NK) cell receptor (pNKR), we recently cloned a novel cDNA and localized this gene to the short arm of human chromosome 3, region 3p21-3p24. Individuals susceptible to or clinically manifesting von Hippel-Lindau disease (VHL) have a genetic defect telomeric to this region on chromosome 3. This defect, resulting in VHL, is manifested by a high incidence of certain tumors. PURPOSE: Based on the location of this gene, we sought to determine if VHL patients have a defect in gene expression of pNKR. METHODS: Because of the proximity of the VHL and pNKR genetic regions, the variable expression of VHL tumors, and the ability of NK cells to target tumor cells, we investigated NK cell activity and other aspects of the immunologic status in 40 members (four branches) of a family with a high incidence of VHL tumors. RESULTS: Individuals affected with VHL and lacking in normal surface expression of pNKR had virtually no NK cell lytic activity. Analysis of genotypes and phenotypes of all subjects revealed that the greatest difference in NK cell lytic activity (P = .0002) was seen when family members exhibited both VHL and pNKR surface expression defects, compared with normal relatives who had neither defect. Furthermore, the lack of NK cell activity strongly correlated (P = .0005) with abnormal pNKR protein surface expression. Of particular interest, individuals who lacked NK cell activity had normal numbers of NK cells. In addition, analysis of leukocyte subsets indicated normal numbers of T and B cells, monocytes, and NK cells in both affected and normal individuals. CONCLUSIONS: These data indicate that although all affected individuals have the cell population responsible for NK cell activity, many have cells low in expression of pNKR and lack functional NK cell activity. Overall, these results indicate that, in addition to a predisposition to the development of neoplasms, VHL patients have a defect in a specific mechanism of natural immunosurveillance that correlates with a defect in expression of a novel large granular lymphocyte pNKR protein. PMID- 1460672 TI - Cancer incidence and mortality in workers exposed to fluoride. AB - BACKGROUND: Although a recent bioassay showed increased frequency of bone cancer in rats with high oral intake of fluoride, the data are reported as equivocal evidence of carcinogenicity. In humans, occupational fluoride exposure may cause skeletal fluorosis, and our earlier follow-up of fluoride-exposed workers showed increased incidence of respiratory cancers. PURPOSE: To further evaluate occupational fluoride exposure as a carcinogenic risk factor, we extended by approximately one decade the follow-up of a cohort of 425 men and 97 women employed for at least 6 months in the period 1924-1961 at the Copenhagen cryolite processing plant. Cryolite ore contains about 50% fluoride. METHODS: Cancer mortality was determined for the period 1941-1989, and incidence for 1943-1987. For comparison, we used national mortality rates and cancer incidence rates for the Copenhagen area. RESULTS: Among the men, 300 deaths occurred; 223 were expected. Respiratory (lung and laryngeal) cancers and violent death were responsible for most of this excess; rates for mortality from cardiovascular disease were close to the rates expected. Of the 423 male workers, 119 developed cancers; 103.6 were expected. There was excess incidence of cancers of the lungs (35 men; standard incidence ratio [SIR] = 1.35), larynx (5 men; SIR = 2.29), and urinary bladder (17 men; SIR = 1.84). Maximum incidence occurred after 10-19 years of employment, but otherwise, no stable relationship between cancer incidence and duration of employment was observed. The incidence of respiratory and urinary cancers was particularly high in men less than 35 years old at first employment. Cancers in female workers were too few to allow detailed evaluation. CONCLUSIONS: The increased incidence of respiratory cancers suggests that cigarette smoking was frequent in this cohort, despite the unremarkable cardiovascular mortality, but the disproportionate increase in the incidence of bladder cancer is difficult to explain by smoking habits alone. Because this industrial cohort was exposed to high concentrations of fluoride dust, heavy respiratory exposure to fluoride may have contributed to the increased cancer risk. If these workers inhaled a carcinogenic substance partly excreted in the urine, an increased incidence of respiratory and bladder cancers would not be inconceivable. IMPLICATION: The potential role of fluoride as a cause of bladder cancer needs to be explored. PMID- 1460673 TI - Growth inhibition of estrogen-dependent and estrogen-independent MXT mammary cancers in mice by the bombesin and gastrin-releasing peptide antagonist RC-3095. AB - BACKGROUND: Many breast cancers are estrogen independent, and even in patients who initially respond to estrogen suppression therapy, the regression is often temporary. We have recently shown that antagonists of bombesin and gastrin releasing peptide, including RC-3095, inhibit the growth of pancreatic, colonic, and prostatic cancers in experimental animals. This effect was associated with a substantial decrease in epidermal growth factor (EGF) receptor levels in pancreatic and colon cancers. PURPOSE: In view of these findings, we investigated the effects of our synthetic bombesin and gastrin-releasing peptide receptor antagonist D-Tpi6,Leu13 psi (CH2NH)-Leu14 bombesin(6-14) (RC-3095) on the growth of hormone-dependent and hormone-independent MXT mouse mammary cancers in vivo. METHODS: Female (C57BL x DBA/2)F1 mice bearing estrogen-dependent or estrogen independent MXT mammary carcinomas were treated with small doses (20 micrograms/d) of RC-3095 administered from osmotic minipumps. Separate groups of mice with estrogen-independent tumors received RC-3095, bombesin, or gastrin releasing peptide(14-27) at 20 micrograms/d. We determined tumor volume and weight, mitotic index, apoptosis (programmed cell death), and argyrophilic nucleolar organizer regions, an indicator of tumor cell proliferation. Levels of receptors for EGF and bombesin were measured in tumor membrane fractions. RESULTS: Growth of both estrogen-dependent and estrogen-independent MXT breast cancers was significantly inhibited by RC-3095. Bombesin or gastrin-releasing peptide had no effect on the growth of estrogen-independent tumors. Inhibition of tumor cell proliferation was indicated by a 45%-65% reduction in tumor volume, a 35%-58% reduction in tumor weight, and statistically significant decreases in argyrophilic nucleolar organizer region counts after treatment with RC-3095. In estrogen-independent cancers, tumor inhibition was associated with a decrease in the capacity of EGF receptors from 0.21 +/- 0.016 pmol/mg membrane protein in controls to 0.03 +/- 0.003 pmol/mg membrane protein in the RC-3095-treated group. CONCLUSIONS: This is the first demonstration of inhibitory effects of bombesin and gastrin-releasing peptide antagonists on the growth of breast cancers in vivo. IMPLICATIONS: These findings suggest that bombesin antagonists should be considered for breast cancer therapy. PMID- 1460675 TI - Reactivation of thermal burn by methotrexate. PMID- 1460674 TI - Karyotypic derivation of H9 cell line expressing human immunodeficiency virus susceptibility. AB - BACKGROUND: The T-cell lymphoma HUT78 cell line and the H9 clone of the CD4 positive HT cell line, derived from HUT78, are known to be genetically identical on the basis of allozyme (allelic isozyme) patterns and DNA fingerprinting, but the chromosome compositions of these cell lines have not been determined. The HT cell line and its H9 clone carry susceptibility to the human immunodeficiency virus (HIV). PURPOSE: The purpose of this study was to examine specific chromosome changes linking the expression of the HIV susceptibility that is unique to H9 cells by characterizing the karyotypes of the HUT78 and the H9 cell lines, by comparing chromosome differences between these lines, and by evaluating the relationships between them. METHODS: Air-dried chromosome slides were prepared, and the fast Giemsa-trypsin method was used to delineate G-bands. The numerical distribution of chromosomes from the two cell lines was determined, and complete chromosome analysis in 47 HUT78 metaphases and 21 H9 metaphases with discernible G-banding was used to specify the modal karyotypes of each cell line. RESULTS: Both cell lines had complex karyotypes that contained 47%-65% structurally modified marker chromosomes. The distribution of numbers of chromosomes in HUT78 cultures was broad. There were two distinct modal numbers of chromosomes at 42 and 43 and at 73, resulting from the presence of three actively growing sublines: two hypodiploid (1s) sublines (HUT78/1sA and HUT78/1sB) and a hypertriploid (2s) subline (HUT78/2s), respectively. HUT78/1sA and HUT78/1sB differed by five reciprocal chromosome replacements, and HUT78/2s had double copies of most of the chromosomes in 1s cells. H9 and HUT78/2s had had 21 matching markers, 10 of which were paired; contained 21 chromosomes with the same number of copies; consistently lacked eight homologous normal chromosomes; and showed close modal numbers of chromosomes at 69 and 73, respectively. CONCLUSIONS: Derivation of the 2s subline from the 1s subline by polyploidization is apparent. All lines apparently had the same progenitor cell population, and HUT78/2s represents an intermediate linking HUT78/1s to H9. IMPLICATIONS: These data should be useful for studying specific chromosome changes linking the expression of the HIV susceptibility unique to H9 cells. Karyologic studies such as those presented here can provide data (a) to clearly identify the clonal cell population of a subline, (b) to examine relationships among sublines of the same progenitor, and (c) to provide a clue that may link a subtle chromosome change to a phenotypic expression. PMID- 1460676 TI - Surveys as a tool for needs assessment of continuing medical education. PMID- 1460677 TI - Health crisis in the minority community: prevention and management. Inaugural address. PMID- 1460678 TI - Primary care at DC General Hospital. PMID- 1460679 TI - Analysis of prehospital delay among inner-city patients with symptoms of myocardial infarction: implications for therapeutic intervention. AB - In this study, we analyzed the duration and determinants of prehospital delay in a group of inner-city patients hospitalized with suspected myocardial infarction. The average prehospital delay was 11.9 +/- 25.1 hours. Mean and median delays were similar for males (mean: 10.9 +/- 24.2 hours; median: 2.8 hours) and females (mean: 12.7 +/- 25.7 hours; median: 3.5 hours), but were longer for blacks (mean: 13.1 +/- 27.5 hours, P < .001; median: 3 hours, P = .06) and Hispanics (mean: 12.4 +/- 19.3 hours, P < .01; median: 4 hours, P = .07) than for whites (mean: 3.3 +/- 2.9 hours; median: 2 hours). Most of the observed delay was due to the time it took for patients to decide to seek medical care following onset of symptoms. Patients were more likely to arrive at the hospital within 4 hours if they thought their symptoms might be a heart attack (79% versus 41%, P < .01), if they believed that coronary heart disease was preventable (68% versus 42%, P < .01), and if they took an ambulance to the hospital (68% versus 47%, P < .01). The factor most strongly associated with early hospital arrival was the patient's belief that the symptoms might represent a heart attack; these patients were five times more likely to get to the hospital within 4 hours than others, independent of other factors. Interventions designed to decrease prehospital delay must focus not only on improving knowledge of symptoms, but also on identifying high-risk patients and increasing patient awareness of the benefits of early response and treatment. PMID- 1460680 TI - Leukoedema: a review of the literature. AB - Leukoedema, a grayish-white lesion of the oral mucosa in humans, was once thought to be a probable precursor to leukoplakia. Clinical examination differentiates leukoedema from leukoplakia, lichen planus, white sponge nevus, and pathomimia morsicatio buccarum. Prevalence rates vary greatly in different countries and in different ethnic groups. For many years, leukoedema was alleged to occur only in adult populations until Martin and Crump found this lesion in children and youth. There is a definite predilection for this lesion in black Americans. Although the etiology is unknown, it has been suggested that leukoedema develops in areas of local irritation. This article reviews the literature related to the prevalence of leukoedema and correlates the independent findings, which might pertain to its etiology. PMID- 1460681 TI - Pitfalls in communication with Hispanic and African-American patients: do translators help or harm? AB - The Martin Luther King County General Hospital, Los Angeles, California, provides services for an equal number of Hispanics (most are recent immigrants from Mexico) and African Americans who have lived in the community since before the Watts riot in 1965. The hospital is staffed by a large percentage of foreign trained doctors and other personnel who speak some English, but suffer from a lack of understanding of the Hispanic as well as the African-American patients. Very few trained interpreters are provided for the Spanish-speaking population, and no interpreters are provided for African Americans. A 100-question survey on common African-American expressions was conducted in the Department of Family Medicine, as well as an opinion poll to determine if adequate understanding existed between patients and providers. The data revealed that native African American providers understood significantly more African-American expressions than foreign, white, and Hispanic providers. The opinion poll also revealed inadequate translation of medical complaints from patients through interpreters. In addition, the poll found that diagnoses and instructions were not adequately related to the patients. Furthermore, it was felt that trained interpreters should be provided for all patients who presented communication problems. PMID- 1460683 TI - Musculoskeletal trauma: the baseball bat. AB - Between July 1987 and December 1990 in Washington, DC, 116 patients sustained 146 fractures and seven dislocations due to an assault with a baseball bat. The ulna was the most common site of trauma (61 fractures), followed by the hand (27 injuries) and the radius (14 injuries). Forty-two of the 146 fractures were significantly displaced and required open reduction and internal fixation to restore satisfactory alignment. Twenty-nine of the 146 fractures were open fractures. Treatment protocol for open fractures consisted of irrigation and debridement, antibiotic therapy, and bone stabilization with either internal or external fixation, or casting. Recognition of the severity of the soft tissue and bone damage is important in the management of musculoskeletal trauma secondary to the baseball bat. PMID- 1460682 TI - Paratesticular liposarcoma: a report of two cases and review of the literature. AB - Paratesticular liposarcoma is extremely rare. Only 41 cases have been reported in the literature. This article reports two cases, reviews the literature, discusses the pathology, and proposes the use of combined surgery and radiation therapy in selected cases. PMID- 1460684 TI - Time-related effects of heparin sulfate on regional and systemic anticoagulation. AB - Optimal timing of vascular clamping to anticoagulation during cardiovascular surgical procedures is poorly defined. This study uses a canine model to determine the effectiveness of three different methods of heparin administration. Heparin sulfate (150 IU/kg) was administered by: injection into the jugular vein 5 minutes before infrarenal aortic clamping (Group 1), injection into the terminal aorta immediately after infrarenal aortic clamping (Group 2), and injection into the jugular vein immediately after infrarenal aortic clamping (Group 3). Thrombin clotting times and partial thromboplastin times were measured in venous blood from the upper and lower extremities before (baseline) heparin administration, and 1, 3, and 5 minutes following heparin administration. Activated clotting times were assessed in lower extremity blood at baseline, and at 1 and 5 minutes after heparin injection. Significant differences existed between groups in both upper and lower extremities. Systemic anticoagulation occurred within 1 minute after intravenous heparin administration in Groups 1 and 2 in the lower extremity, and Groups 1 and 3 in the upper extremity. Delayed anticoagulation in the lower extremity was noted with systemic injection after aortic clamping in Group 3, and after regional intra-aortic administration in the upper extremity of Group 2 subjects. Complete anticoagulation was noted by 5 minutes in all groups in both the upper and lower extremities. These results suggest that the safe time period between heparin administration and vascular clamping varies with the route and the timing of its administration. Intravenous administration prior to aortic cross-clamping provided adequate anticoagulation in this canine model in both the upper and lower extremity blood after 1 minute of heparin circulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460685 TI - Neuroleptic malignant syndrome. AB - Neuroleptic malignant syndrome is a life-threatening reaction of neuroleptic medication. The estimated incidence rate of neuroleptic malignant syndrome is between 1% and 1.5% of patients treated with neuroleptics. The reported mortality rate varies from 11% to 38%. Risk factors include younger males (80% less than 40 years) and physical disability. Although 80% of neuroleptic malignant syndrome cases develop within the first 2 weeks of treatment, the syndrome can develop anytime during the therapy period. The clinical picture and laboratory findings are not always unique. Less than 50% of cases manifest with classical symptoms. Deaths usually result from cardiovascular collapse. Renal failure, pulmonary emboli, aspiration pneumonia, and respiratory failure are also reported. Familiarity with the syndrome, baseline laboratory values including creatine phosphokinase, lactate dehydrogenase, serum glutamicoxaloacetic transaminase, and complete blood cell count with a differential count, and a high index of suspicion are of the utmost importance in making the diagnosis of neuroleptic malignant syndrome. A judicial choice of neuroleptic medication and careful observation of patients may reduce the incidence, morbidity, and mortality of neuroleptic malignant syndrome. PMID- 1460686 TI - Injuries to the bowel and bladder. AB - The initial challenge facing the traumatologist in the management of bowel and bladder injuries is prompt diagnosis. Intestinal perforations following penetrating trauma are caused by direct penetration or by blast effect, and are most commonly diagnosed by physical examination (signs of peritoneal irritation) or peritoneal lavage. Bowel rupture from blunt trauma is more difficult to diagnose and results from different mechanisms of injury including crushing between the spinal column and the offending blunt object, shearing of the bowel and mesentery at fixed points from sudden deceleration, and rupture secondary to sudden increase in intra-abdominal pressure. Bladder rupture is most commonly seen in association with pelvic fractures, and the diagnosis is made by a well performed cystogram. This article presents essentials for diagnosis and therapeutic strategies. PMID- 1460687 TI - Fused pelvic kidneys: case report. AB - A case of fused pelvic kidneys is presented. We believe this to be the first report using ultrasound, computed tomography, and magnetic resonance imaging for presentation of a rare anatomic renal anomaly. PMID- 1460688 TI - The American doctor who was neither, but a hero nonetheless. PMID- 1460689 TI - Forensic psychiatry. PMID- 1460690 TI - Decision tree for the management of substance-abusing psychiatric patients. AB - This paper describes a short-term approach developed at a time of numerous drug related incidents occurring at a large VA Hospital to help staff manage psychiatric patients abusing alcohol or drugs during hospitalization. This was accomplished through the development of a decision tree designed to improve the clinical problem-solving process by identifying key decision points. Prior to this, staff responded emotionally either by prematurely discharging patients or by not recognizing the problem at all. Decision Trees have widespread applicability for resolving complex clinical problems. PMID- 1460691 TI - Therapist techniques used during the cognitive therapy of opiate-dependent patients. AB - A review of current substance abuse literature indicates that although clinicians espouse cognitive and behavioral methods in the treatment of drug-dependent patients, little is known about the process of cognitive-behavioral therapy with these individuals. Our objective is to examine the specific techniques used by manual-guided cognitive-behavioral therapists during the treatment of opiate dependent patients. Ratings of audiotaped sessions using the Collaborative Study Psychotherapy Rating Scale indicate that the cognitive-behavioral therapists did not rely on behavioral methods early in treatment as predicted by both theory and the clinical literature. Cognitive techniques and techniques oriented toward establishing a collaborative structure predominated and increased from early- to late-in-treatment sessions. We discuss the implications of the results in terms of treatment manual revisions and directions for future research. PMID- 1460692 TI - Psychological treatment of anabolic-androgenic steroid-dependent individuals. AB - Anabolic-androgenic steroids (AAS) are synthetic derivatives of the sex hormone testosterone. Anabolic refers to the "growth-promoting" effect while androgenic refers to the "masculinizing" effect. It is becoming more evident that nonathletes as well as athletes are abusing AAS. Although the abuse of alcohol and other drugs contribute significantly to current chemical use problems in American society, AAS abuse is one of the fastest growing "new drug" problems facing secondary and higher education institutes of learning. The purpose of this discussion is to present working hypotheses regarding the psychological treatment of AAS dependent individuals. The treatment approach presented incorporates the approaches used with eating disorders, substance abuse/dependence, and narcissistic personality disorders. This paper considers some of the preliminary considerations for the first phase of treatment, some pitfalls to avoid, and therapist characteristics, as well as treatment modalities that might be helpful in the treatment of AAS-dependent individuals. PMID- 1460693 TI - Safe sex behavior in drug-addicted males as a function of object relations. AB - An inventory of sexual behavior was administered in a hospital detoxification program to 127 drug-addicted males, who also completed a modified form of the Defense Mechanisms Inventory (DMI) which yields a measure of object relations. Condom use was shown to be related to an object relations mode that typifies the individual who can structure reality and needs without requiring an integral aspect of "the other" in his approach. Standardization and factor analytic data are also presented for the DMI and the object relations measure for this population. The resulting pattern and the small effect size are discussed within the reality constraints of the addicted patient, as well as within the psychometric parameters inherent in psychoanalytic research. PMID- 1460694 TI - Assessing drug abusers with the Millon Clinical Multiaxial Inventory: a review. AB - This paper reviews studies that used the Millon Clinical Multiaxial Inventory with drug abusers. Although the test has been used with over 2000 such patients in the published literature, there is still a dearth of basic research with the MCMI with this population. Preliminary evidence suggests that the Personality Disorder Scales are quite useful to assess personality styles of drug abusers, but the Clinical Syndrome Scales present some problems. Specifically, the Drug Dependence Scale has had difficulty in reliably "detecting" drug addicted individuals who were in treatment for drug abuse. However, a reliable modal MCMI profile among this population seems to exist, although cluster research suggests several subtypes, each with different personality styles. MCMI computer-narrative reports may overdiagnose paranoid disorder and under diagnose antisocial disorders among this population. PMID- 1460695 TI - Pathogenesis and ecology: the case of cholera. AB - The way in which the results of various studies of cholera have influenced the understanding of the disease are discussed. Attention is given to the outcomes of medical research, targeted on problems of cholera and biological research focused on understanding Vibrio cholerae. The contrast between these approaches has produced a new understanding of the ecological nature of disease. The importance of the environmental reservoir of V. cholerae as the engine for the generation of diversity is highlighted. PMID- 1460696 TI - The EPI in Borno State, Nigeria: impact on routine disease notifications and hospital admissions. AB - An earlier report on the Nigerian expanded programme on immunization (EPI), covering 1974-1988, failed to demonstrate a clear-cut impact of the programme. This report attempts to determine the effectiveness of EPI in Borno State, Nigeria. We analysed trends in routine notifications for diphtheria, pertussis, tetanus, tuberculosis, measles, and pneumonia, from 1985 to 1991; data on poliomyelitis were excluded because of poor documentation, while we included data on pneumonia for comparison. We also performed a before (1983-1987) after (1988 1991) comparison in terms of the intensifications of EPI by age-specific strata amongst paediatric hospitalization for all EPI diseases at the University of Maiduguri Teaching Hospital, the sole referral hospital for childhood infectious diseases. Our results show an apparent reduction in morbidity from diphtheria, pertussis, tetanus, measles and pneumonia, and this was particularly prominent following intense vaccinations between 1988 and 1991. The reduction in these EPI diseases and pneumonia occurred despite the prevailing adverse socioeconomic conditions, and the absence of a specific control strategy for pneumonia in Nigeria. On the other hand, in spite of national BCG coverage of about 90% there has been a recent (1989-1991) increase in the registered cases of tuberculosis in infants and older children in Borno State. There is a need to intensify other intervention measures alongside EPI activities. PMID- 1460697 TI - The effect of malaria on work time: analysis of data from two Nepali districts. AB - Malaria patients' loss of effective work time can account for an important proportion of the disease's economic cost. Here the extent, incidence and determinants of this loss are investigated. Data from 695 matched patient-control pairs from Nawal Parasi and Dhanusa districts in Nepal are analysed. Pairwise differences in work time are attributed to malaria, and the individual influences of the differences' determinants identified by regression. The mean pairwise differences in the number of days wholly and partially disabled by illness in the month preceding interview were respectively 5.31 (95% confidence interval 4.82 5.79) and 1.21 days (95% CI 0.95-1.47). The interval between fever onset and presumptive treatment, parasite species, the density of peripheral parasitaemia and district of residence each exerted significant influences over the difference in complete disability. The mean pairwise difference in the number of minutes worked on the day before the interview was 108 (95% CI 97-120). Socioeconomic variables, the interval between interview and perceived complete recovery, the pairwise difference in the number of days' complete disability in the month preceding interview and district of residence were significant to this difference. Poorer patients lose more time. The results corroborate past assumptions of debility, demonstrate that malaria's effect on effective work time may vary between socioeconomic groups, and underline the economic importance of speedy case detection and presumptive treatment. PMID- 1460698 TI - Schistosoma mansoni: cercaricidal effects of cedarwood oil and various of its components. AB - Cercariae of Schistosoma mansoni exposed to cedarwood oil show early phases of the penetration response before they succumb to the toxic effects of the oil. The toxic effect is also seen when cercariae are exposed to certain components of the oil followed by exposure to a known penetration stimulant, linolenic acid, which accelerates the inactivation of the organism. It is postulated that the process of penetration which results in the disruption of the cercarial glycocalyx alters physiological processes related to osmoregulation. This may increase the absorption of the toxic substances in cedarwood oil by the organisms. PMID- 1460699 TI - Antibacterial agents for wounds and burns in the developing world. Report on a workshop. AB - Publications on the use of antibacterial agents for wounds and burns in the developing world continue to emphasize the value of antiseptics such as Eusol and gentian violet. In the developed world these agents have been mostly discredited. A workshop organized by the European Society for Tissue Repair concluded that clearer instructions about the role of antibacterial agents in the management of wounds and burns could clarify appropriate usage. The report considers the factors contributing to infection and rationalizes the use of disinfectants, antiseptics and antibiotics, especially in the developing world. PMID- 1460700 TI - The impact of Schistosoma haematobium infection and of praziquantel treatment on the growth of primary school children in Bertoua, Cameroon. AB - Our objective was to determine in a Cameroonian school population the effect of mild to moderate S. haematobium infection intensity on growth and development of children before and 6 months after praziquantel treatment. Previous studies have yielded contradictory results. Children from Bertoua schools were divided into four study groups: heavily infected (> 500 eggs 10 ml-1), moderately infected (1 499 eggs 10 ml-1) treated with praziquantel, a similar group treated with placebo, and an uninfected control group. Anthropometric measures--height for age per cent median (HAPM), and weight for age per cent median (WAPM)--were significantly higher among the uninfected children. Stepwise regression analysis showed that S. haematobium and Ascaris infections were the strongest predictors of the HAPM with hookworm and malaria infections playing a lesser role. Post treatment comparison of the praziquantel treatment group and the placebo group showed no significant differences for the anthropometric indicators except for mid-arm circumference. Longer observations of growth after treatment as well as monitoring of the rate of reinfection would be necessary to understand better the effect of S. haematobium on growth. PMID- 1460701 TI - Cervical lymphadenopathy in Khartoum. AB - In this prospective study, 92 patients with cervical lymphadenopathy presenting at Khartoum Teaching Hospital were studied. The commonest cause was found to be tuberculous cervical lymphadenitis (TCA) comprising 49%, followed by malignancy (35%) including both primary neoplasm (15 cases) and metastatic lesions (17 cases). The tuberculous group were young patients mainly from low socioeconomic classes. The most affected nodes were in the posterior triangle, followed by upper jugular and supraclavicular nodes. In the malignant group, half the patients had primary reticulo-endothelial neoplasm and the other half had metastatic tumours, most often from the nasopharynx. The triad of symptoms of fever, fatigue and loss of weight was found equally in tuberculous and lymphoma patients. Hence empirical use of antituberculous therapy without histological diagnosis resulted in delay in diagnosis of malignancy. Antituberculous therapy should be preceded by histological proof wherever possible. PMID- 1460702 TI - The effect of plastering in a house persistently infested with Triatoma infestans (Klug) 1934. AB - The replastering of a house in Mambai-Goias, Brazil, as a measure to wall-in Triatoma infestans, is briefly described. Unfortunately, because the houseowner would not cooperate the roof tiles were not improved and eventually T. infestans reappeared at this site. A brief discussion follows of some aspects of house improvement in the vigilance phase of a Chagas Disease Control Programme. T. infestans appeared in the house described 51 and 258 days after the replastering. PMID- 1460703 TI - Detection of rifampicin-induced nephrotoxicity by N-acetyl-3-D-glucosaminidase activity. AB - The objective of the present study was to assess renal damage, if any, by non invasive technique, viz NAG activity in urine and GFR in patients on continuous and intermittent rifampicin therapy. Eighty-four tuberculosis patients for cross sectional study and six subjects for longitudinal study on antitubercular therapy and ten patients on withdrawal of rifampicin participated in the investigation; 13 leprosy patients intermittently treated with rifampicin were also included. Twenty-seven normal subjects served as controls. Rifampicin on continuous use resulted in a progressive increase in enzymuria with no change in GFR. An additive toxic effect was obvious in patients receiving streptomycin; when the treatment was withdrawn the urinary NAG activity stabilized within 15-21 days. However, patients receiving rifampicin intermittently did not show any evidence of renal damage. The results suggest that there is a need for monitoring renal damage, particularly on antitubercular therapy, when nephrotoxic agents are administered together. PMID- 1460704 TI - Locally acquired cutaneous leishmaniasis in Sri Lanka. AB - Cutaneous leishmaniasis in a Sri Lankan, who had not left the country, is reported. The diagnosis was confirmed by detecting the parasite in smears under microscopic examination. This is the first case report of locally acquired leishmaniasis in Sri Lanka. PMID- 1460705 TI - Vascular surgery into the twenty-first century. PMID- 1460706 TI - Magnetic resonance angiography of peripheral runoff vessels. AB - Recent improvements in magnetic resonance imaging techniques have made magnetic resonance angiography (MRA) a very useful adjunct to invasive angiography. Fifty five limbs in 51 patients with occlusive peripheral vascular disease were studied with both MRA and contrast arteriography. The magnetic resonance and contrast arteriograms were read by radiologists and surgeons and separate interventional plans were based on each study. The MRA findings differed significantly from those of conventional arteriography in 26 limbs (48%). In every case MRA visualized all of the same vessels and hemodynamic stenoses seen on the contrast arteriogram. In 48% of the cases, however, MRA revealed additional findings. Thus the discrepancies in the two studies were always the result of the failure of the arteriogram to reveal all of the patent vessels seen on MRA. The additional information provided by MRA resulted in alteration of the interventional plan in 11 cases (22%). In nine cases (18%) target vessels suitable for use in a limb salvage procedure were identified by MRA, although they had been missed by conventional arteriography. In all of these cases, intraoperative arteriograms confirmed the suitability of these vessels for use in technically successful bypass procedures. In two cases (4%) additional information provided by MRA identified a target runoff vessel for bypass grafting that proved to be a better alternative than the one that would have been chosen on the basis of contrast arteriography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460707 TI - Polytetrafluoroethylene versus human umbilical vein in above-knee femoropopliteal bypass: six-year results of a randomized clinical trial. AB - In a prospective, randomized trial 6 mm polytetrafluoroethylene (PTFE) and 6 mm human umbilical vein (HUV) were compared in above-knee femoropopliteal bypass grafting. In claudicants a prosthetic graft was used intentionally, in limb salvage cases only when autologous vein was insufficient. Ninety-six extremities were randomized (49 PTFE and 47 HUV). Operative indication was disabling claudication in 77 and limb salvage in 19 extremities. The two groups were comparable as to preoperative risk factors and operative and postoperative treatment. Median follow-up was 76 months (range 47 to 91 months), during which 23 patients died of nonrelated causes with functioning grafts. Thirty-eight grafts failed (33 because of occlusion and five for other reasons). At 6 years the primary patency rate was 38.7% in the PTFE group and 71.4% in the HUV group (p < 0.001). Corresponding rates for secondary patency at 6 years were 51.4% and 76.4% (p < 0.005). PMID- 1460708 TI - Transfusion guidelines for cardiovascular surgery: lessons learned from operations in Jehovah's Witnesses. AB - Patients undergoing cardiovascular surgery are among the top users of homologous blood transfusion (HBT). Awareness of the risks of disease transmission and immune system modulation from HBT has prompted us to find alternatives such as autologous predonation (APD) and intraoperative autotransfusion (IAT). However, these latter options are not appropriate for all patients. We reviewed our experience with 59 Jehovah's Witness patients who underwent 63 elective cardiovascular procedures without either HBT or APD to determine the safety of operation without these modalities and to develop revised maximum surgical blood ordering schedule guidelines for cardiovascular surgery. Estimated blood loss averaged 870 ml, but one third to one half of losses were replaced by IAT. IAT was not needed in lower extremity bypass operations in which the estimated blood loss was less than 150 ml. Three of 59 patients died (5.1%), but only one died of operative bleeding complications. We conclude that (1) elective cardiovascular operations can be done safely without the use of either HBT or APD, (2) HBT is not necessary in leg bypass procedures, and (3) maximum surgical blood-ordering schedule guidelines for HBT in major cardiovascular operations can be reduced to near zero by the use of intraoperative autotransfusion and acceptance of a postoperative hemoglobin nadir of 7.0 gm/dl. PMID- 1460710 TI - Iliofemoral versus femorofemoral bypass: the case for an individualized approach. AB - The treatment of unilateral iliac occlusion remains controversial. We report our experience with femorofemoral bypass (FF) and iliofemoral bypass (IF). One hundred sixty-two FFs and 82 IFs were performed during a 25-year period. Demographic characteristics of the two groups were similar. Operative indications included claudication in 32.1% of FFs and 19.5% of IFs, rest pain in 26.5% of FFs and 36.6% of IFs, ulcer in 8.0% of FFs and 3.7% of IFs, gangrene 13.6% of FFs and 23.2% of IFs, and acute thrombosis in 13.0% of FFs and 3.7% of IFs. Five-year primary and secondary patency rates for all FFs were 56.9% and 65.4% respectively. Those for all IFs were 74.9% and 79.2%. The primary patency rate of FF performed for chronic arterial occlusive disease was 73.3% at 3 years and 60.4% at 5 years and for IF it was 73.4% at 3 years. In the absence of prior arterial surgery in the groin, the primary patency rates of bypasses for chronic arterial occlusive disease were 78.3% for FF and 86.8% for IF at 4 years. Distal endarterectomy and acute ischemia adversely affected patency. The operative mortality rate was 6.2% for FF and 3.7% for IF. Eleven wound complications occurred in the FF group. Seven patients underwent graft removal without limb loss. One minor wound problem occurred in the IF group. Iliofemoral bypass avoids operation on an asymptomatic limb; FF avoids entry in the abdomen or retroperitoneum and can be performed under local anesthesia. In patients in whom either IF or FF is applicable, the choice between these two procedures should be individualized with these factors in mind. PMID- 1460709 TI - Treatment of iatrogenic femoral artery injuries with ultrasound-guided compression. AB - Iatrogenic injuries of the groin are becoming more common after increasingly sophisticated vascular intervention. These injuries are accurately detected by duplex and color Doppler ultrasonography. Recent treatment of these lesions by ultrasound-guided compression repair (UGCR) has been described. During a 1-year period we identified 18 femoral artery injuries, including 17 pseudoaneurysms and one arteriovenous fistula. Three of the pseudoaneurysms thrombosed spontaneously before attempted treatment. The remaining 15 lesions underwent a trial of UGCR. Successful closure was accomplished in 10 patients (56%). Seven of these lesions were successfully treated during the initial session, and thrombosis was accomplished after repeat compression in three additional lesions. Three patients who were given anticoagulants had a failed UGCR, but their pseudoaneurysms thrombosed after administration of anticoagulants was discontinued. Two patients had failed UGCR and required operation. Seven (88%) of eight patients who were not given anticoagulants were successfully treated. In contrast only two (29%) of seven patients given therapeutic doses of anticoagulant medication were successfully treated by the technique. There was no statistical difference between mean pseudoaneurysm diameter, mean width and length of pseudoaneurysm neck, or depth of pseudoaneurysm neck from skin surface in patients in whom successful initial closure was achieved when compared with those patients in whom the initial attempt failed. UGCR is a safe, simple, noninvasive technique that can be used to treat many femoral artery injuries that traditionally were treated with surgery. The technique can be applied by any laboratory that has the necessary ultrasonography equipment and is currently the method of choice for treating uncomplicated iatrogenic femoral artery injuries at our institution. PMID- 1460711 TI - Aneurysmal change at or above the proximal anastomosis after infrarenal aortic grafting. AB - We conducted a retrospective review of all patients undergoing repair of abdominal aortic aneurysm at or above the proximal anastomosis of a previous infrarenal aortic graft between 1986 and 1991. Infected grafts and patients with suprarenal aneurysms present at the time of the original graft were excluded. Twenty-one patients, 19 men and two women, were included. The original indication for surgery was aneurysm in 14 patients and occlusive disease in seven; the mean interval from initial surgery to presentation was 10 years (range, 3 to 23 years). Twelve lesions were anastomotic false aneurysms, and nine were true aneurysms beginning in the proximal juxta-anastomotic aorta. Fourteen patients had an asymptomatic abdominal mass. Seven patients had symptoms of acute expansion (three), rupture (three), or thrombosis (one). True aneurysm and symptomatic presentation were correlated with aneurysm as the original indication for surgery. Repair was accomplished by an interpositional graft in 13 and graft replacement in eight. Seven patients required suprarenal anastomosis or renal and visceral reconstruction. Five operative deaths (24%) occurred, including two of three patients with rupture (67%) and two of seven patients (28%) in the suprarenal group. The mortality rate for elective repair with an infrarenal anastomosis was 11%. Two additional late deaths occurred during the follow-up period. PMID- 1460712 TI - Treatment of angioaccess-induced ischemia by revascularization. AB - Upper extremity ischemia related to the construction of a chronic angioaccess is a serious and occasionally devastating complication. Fourteen patients with end stage renal disease (mean age 58 +/- 18 years, 13 with diabetes, 10 female) had ischemia after construction of an angioaccess. Twelve patients had a polytetrafluoroethylene brachioaxillary bridge arteriovenous fistula (BAVF), one patient had a radiocephalic arteriovenous fistula (AVF) and one patient had a brachiocephalic AVF. All patients had severe ischemia and five of them had established gangrenous changes. Symptoms appeared immediately after construction of the access in 10 patients. The remaining four patients had late onset of ischemia. The technique used for revascularization in all of these patients consisted of ligating the artery just distal to the takeoff of the AVF or BAVF and establishing an arterial bypass from a point proximal to the AVF or BAVF inflow to a point distal to the ligature. Bypass grafts consisted of saphenous vein in 13 cases and polytetrafluoroethylene in one case. Thirteen patients had a complete recovery, including healing of gangrenous lesions. One patient with severe gangrene of the hand at the time of revascularization required forearm amputation 13 months later because of progressive occlusive arterial disease. All AVFs were patent at 1 year. The 1-year patency rate for the BAVFs was 81.7%. All arterial bypasses were patent at 1 year. It is concluded that this technique offers consistent and durable hemodynamic and clinical improvement in arms affected by access-induced ischemia, with minimal morbidity, and does not affect the longevity of the angioaccess. PMID- 1460713 TI - Natural history, duplex characteristics, and histopathologic correlation of arterial injuries in a canine model. AB - The treatment of patients with penetrating extremity trauma in proximity to major arteries as well as the nonoperative treatment of clinically occult arterial injuries remain controversial. Duplex ultrasonography (DUS) has recently been advocated in this setting. We therefore studied experimentally induced arterial injuries in dogs to correlate the natural history, duplex findings, and histopathologic condition of different injuries and to help define criteria for operation. Fifty-two canine femoral and carotid arteries were randomized to have surgically created intimal flaps (n = 15), crush injuries (n = 15), or lacerations (n = 15) or to be controls (n = 7). An experienced sonographer, blinded to the presence or type of injury, evaluated the vessels every 10 days for 1 month. Histopathologic study was performed 1 month after injury when the arteries were retrieved. The sensitivity (96.5%), specificity (86.4%), and accuracy (95.1%) of DUS in evaluating arterial injuries at 1 month correlated well with histopathologic evaluation. All arteries subjected to crush injuries showed abnormal duplex findings. These findings correlated well with the histologic picture of severe injury (arterial wall thickness = 2.72 x +/- 0.23 x control; intramural hemorrhage, 93%; mural thrombus, 60%). DUS and histologic study revealed healing of intimal flaps in 27% of the arteries. Other intimal flaps deteriorated (stenoses, 47%; dilation, 13%; occlusion, 13%). Most lacerations (86%) revealed duplex evidence of healing within 10 days of injury. This was confirmed by histologic study at 1 month in 73% of lacerated arteries. This study confirms the accuracy of DUS in diagnosing various arterial injuries and shows that the natural history of these injuries varies with the mechanism of injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460714 TI - Infrapopliteal arterial injury: prompt revascularization affords optimal limb salvage. AB - Sixty-nine limbs with infrapopliteal arterial injuries were evaluated in 68 patients. Thirty-five (50%) cases were complicated by acute limb-threatening ischemia. Management consisted of revascularization (26 limbs), ligation (15 limbs), fasciotomy only (2 limbs), observation (18 limbs), and primary amputation (8 limbs). Penetrating injuries (n = 35) had a 33% incidence of ischemia and a reduced frequency of associated injury. One delayed amputation (3%) was required. In contrast, blunt injuries (n = 34) had a 68% incidence of ischemia and a greater frequency of associated injury. There were 20 amputations in the blunt group, including eight primary amputations performed in limbs with profound ischemia, complex open fractures, severe soft-tissue damage, and neural injury. Observation or ligation of single arterial injuries resulted in no early amputations. Associated local injuries in both groups included fracture or ligamentous disruption (64%), severe soft-tissue damage (32%), and nerve dysfunction (36%). In both groups, 15 of 35 ischemic limbs were salvaged by prompt revascularization (11 penetrating and four blunt injuries). Aggressive revascularization with autogenous repair or bypass is recommended for management of penetrating trauma. Though a good outcome will be achieved in some patients with combined blunt trauma and infrapopliteal arterial injury, the probability of delayed amputation and prolonged disability must be consciously integrated into the decision to pursue limb salvage. The prognosis for blunt injury complicated by arterial ischemia is poor; thus the severity of associated local and remote injuries will affect the results of revascularization program. PMID- 1460715 TI - Central and regional hemodynamics determine optimal management of major venous injuries. AB - Controversy continues in the selection of optimal management of major venous injuries. We analyzed our experience with 191 major venous injuries in 163 patients (1986 to 1991). The mechanism of injury was gunshot (112), stab (44), blunt (six), and iatrogenic (one). Eighteen cervicothoracic, 51 caval, 30 iliac, 36 visceral, and 56 extremity veins were involved. Of the 191 injuries, 105 (54.9%) were repaired (lateral repair 76, end-to-end anastomosis 15, vein patch four, vein graft five, Gore-Tex graft four, and compilation one). Of the remaining venous injuries, 64 were ligated as a result of hemodynamic instability. Twenty-two injuries in 18 patients did not receive treatment because 16 of 18 patients died before vascular control or repair. The overall amputation rate was 1.2%, and the mortality rate was 28.2% (46/163). The highest mortality rate occurred in those patients who required resuscitative thoracotomy (100%, p < 0.00001), retrohepatic caval injuries (90%, p < 0.0004), and multiple venous injuries (81.8%, p < 0.00001). Seventeen patients underwent fasciotomies (15 prophylactic and two therapeutic). Clinical or measured venous hypertension by stump pressure assisted in deciding for venous repair in 20 patients. A significant decrease in venous stump pressure (p < 0.000001) was noted after venous reconstruction. Thus the decision to ligate or repair venous injuries correlated primarily with (1) hemodynamic stability, and in stable patients, with (2) extent and location of injury and (3) clinical and measured venous hypertension. Venous ligation in clinically stable patients did not increase the need for fasciotomy or amputation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460716 TI - Management of peripheral vascular problems in recipients of cardiac allografts. AB - Five hundred and twenty consecutive heart transplant cases (458 adult, 62 pediatric) were reviewed to assess the impact of peripheral vascular problems. Peritransplant interventions requiring vascular cannulation (e.g., intraaortic balloon pump procedures, catheterization of the right and left sides of the heart, femoral bypass) resulted in 10 complications that necessitated nine surgical procedures. Five aortic aneurysms (three infrarenal and two suprarenal) were resected. There was one death unrelated to the aneurysm resection. Sixteen patients had evidence of peripheral vascular disease (PVD). There were three deaths in this group, none directly related to the PVD. Three patients required vascular reconstruction (axillobifemoral, bilateral femoral distal and popliteal endarterectomy) in the posttransplant period, all for advanced ischemic symptoms. Except for one patient in whom ischemia-related ulcers developed on the heels, all patients had improved or stable symptoms that did not require intervention. There were no limb losses or vascular infections. We conclude that despite the rigors of posttransplant immunosuppression, patients with stable manifestations of PVD may successfully undergo heart transplantation and subsequent vascular reconstruction, when indicated, without prohibitive risk. PMID- 1460717 TI - The influence of human immunodeficiency virus infection and intravenous drug abuse on complications of hemodialysis access surgery. AB - To examine the influence of human immunodeficiency virus (HIV) infection on complications in dialysis access surgery, a review was performed on patients undergoing hemodialysis at two major metropolitan medical centers over a 30-month period. One hundred eight patients underwent a total of 169 graft procedures; mean follow-up was 14 1/2 months. There were 18 (17%) patients who were HIV positive who had no symptoms, 11 (10%) patients with acquired immunodeficiency syndrome (AIDS), and 79 (73%) patients who were HIV-negative. Twenty-three percent (25/108) of patients had a history of intravenous drug abuse (IVDA), most of whom also had either AIDS or asymptomatic HIV infection. Dialysis procedures included 44 autogenous reconstructions (26%), 117 polytetrafluoroethylene (PTFE) grafts (69%), and 8 (5%) procedures of unknown type. Arteriovenous fistula or graft thrombosis was a frequent complication. The overall 12-month graft patency rate was 41%, and patients with HIV infection or a history of IVDA did not have a significantly increased risk of thrombosis. Multivariate analysis showed that the use of PTFE as opposed to autogenous reconstruction was the only significant risk factor found for occlusion within the first 12 months after operation (p < 0.01). Twenty-five graft infections occurred, all in PTFE grafts. The PTFE graft infection rate was 43% in patients with AIDS, 36% in patients who were HIV positive and who had no symptoms, and 15% in patients who were HIV-negative (p < 0.05). Patients with a history of IVDA had a 41% PTFE graft infection rate versus a 13% infection rate in patients who did not have a history of IVDA (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460718 TI - Comparison of descending phlebography with quantitative photoplethysmography, air plethysmography, and duplex quantitative valve closure time in assessing deep venous reflux. AB - To assess the role of noninvasive tests--quantitative photoplethysmography, air plethysmography, and quantitative duplex scanning, we compared a group of normal (group N, eight limbs) volunteers to patients with severe chronic venous insufficiency who were stratified according to the degree of reflux seen on the current "gold standard," descending phlebography. Group M (10 limbs) had mild (grades 0 to 2) reflux, and group S (10 limbs) had severe (grades 3 to 4) reflux as determined by phlebography. Quantitative photoplethysmography could identify normal from abnormal limbs but could not distinguish the severity of reflux. Air plethysmography was used to calculate venous filling index, ejection fraction, and residual volume fraction. Ejection fraction was the same in all groups. Venous filling index could not significantly distinguish the degree of reflux (group M vs group S) but increased as reflux increased. Residual volume fraction was considerably higher in group S. Quantitative duplex valve closure time was measured in the superficial femoral and popliteal veins, with the values added together in each limb to give a total valve closure time (TVCT). A TVCT value greater than or equal to 4 seconds correlated best with severe phlebographic reflux, with a sensitivity of 90%, a specificity of 94%, and an accuracy of 93%. This value was confirmed as the best test for venous reflux by receiver operating characteristic curve analysis. Thus in the evaluation of patients with severe chronic venous insufficiency who are candidates for phlebography and surgery, quantitative duplex measurement of TVCT gives the best noninvasive assessment of the severity of deep venous reflux. PMID- 1460719 TI - Late complications of revascularization for radiation-induced arterial disease. AB - During a 14-year period 23 patients underwent 25 revascularizations for radiation induced arterial obstructive disease. An average of 5000 rads was delivered, 3 to 24 (mean 9) years before arterial insufficiency, for malignancies of the following origin: gynecologic (n = 9), lymphoma (n = 7), head and neck (n = 5), testicular (n = 1), and lower extremity sarcoma (n = 1). Arterial occlusive disease occurred in the aortic arch vessels (n = 8), visceral aortic vessels (n = 1), and aortofemoral vessels (n = 16). Presenting symptoms were claudication (n = 8), rest pain or nonhealing ulcers (n = 7), transient ischemic attacks (n = 6), asymptomatic bruit (n = 1), and renal insufficiency (n = 1). Reconstructive operations included anatomic bypass (n = 10), extra-anatomic bypass (n = 4), patch angioplasty (n = 5), endarterectomy (n = 3), and resection with interposition graft (n = 1). In this group of patients there were no major perioperative wound complications or other major radiation-associated morbidity. Five patients had late graft infections that manifested from 2 to 5 years after surgery. All occurred in anatomic regions where the bypass graft passed through previously irradiated tissues. Presenting symptoms of infection included a draining groin sinus (n = 3) or soft tissue abscess (n = 2). In all cases the graft had not incorporated into the surrounding tissues when passing through the irradiated area. Treatment included graft excision and extra-anatomic bypass through nonirradiated tissue. One patient died of systemic sepsis. Vascular reconstructive surgery can safely be performed for radiation-induced arterial disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460720 TI - Carotid endarterectomy: a safe cost-efficient approach. AB - The diagnosis-related groups have encouraged physicians to become more efficient in the care of their patients; often, however, raising the question of safety. For 3 years all patients undergoing carotid endarterectomy at our institution were monitored in the intensive care unit for 24 hours and the majority were discharged on the second postoperative day. After review of these patient's hospital records and direct patient interviews, it was clear that many patients did not require a stay in the intensive care unit and could be discharged on the first postoperative day. In January 1991 a prospective policy was established to evaluate the safety and efficacy of outpatient arteriography, same-day admission, selective use of the intensive care unit, and early discharge on the first postoperative day when feasible. During a 10-month period all patients undergoing carotid endarterectomy at our institution were evaluated (n = 52). Eleven patients had had a prior stroke (21%), 31 had either amaurosis fugax or transient ischemic attacks (60%), and 10 had no symptoms (19%). The arteriogram for 49 of the patients was obtained on an outpatient basis or during a prior admission, and these patients were admitted to the hospital on the day of operation. Nine patients were placed under general anesthesia and had shunting procedures, and 43 patients had cervical block anesthesia, eight of whom had shunting (19%). Only five patients required an intensive care unit stay for either hypertension, hypotension, or neurologic complication (one transient ischemic attack and one minor stroke). Forty-six patients (88%) were discharged on the first postoperative day; average length of stay was 1.29 days/patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460721 TI - Routine postendarterectomy duplex surveillance: does it prevent late stroke? AB - Our recent finding that less than 50% of late postendarterectomy strokes are related to recurrent carotid stenosis led us to question the utility of routine postendarterectomy duplex surveillance (RpCEADS) in the prevention of late stroke. To evaluate our RpCEADS program, we reviewed our postoperative duplex studies and correlated their results with clinical data. A total of 1053 postendarterectomy scans was carried out on 348 carotid arteries (258 patients) (3.0 +/- 0.1 studies/artery) during an average follow-up of 52.6 (+/- 2.3) months. Less than 50% of recurrent carotid stenosis was documented throughout follow-up in 292 (83.9%) of 348 arteries. Recurrent carotid stenosis of greater than 50% or occlusion of either the common or internal carotid artery was noted in the remaining 56 arteries (16.1%). Of the 56 duplex-detected recurrent stenoses, only two (3.6%) resulted directly in an unheralded stroke, whereas eight (14.3%) underwent prophylactic reoperation, eight (14.3%) resulted in transient ischemia requiring reoperation, eight (14.3%) occluded without causing stroke, and 29 (51.8%) remained asymptomatic and did not progress to occlusion. Assuming that each of our eight patients who underwent prophylactic reoperation would have had a stroke if operation had not been carried out and our two unheralded strokes could have been prevented with more rigorous follow-up, RpCEADS might have prevented late stroke related to 10 (2.9%) of 348 arteries in 10 (3.9%) of 258 patients after surgery. All other cases of duplex-detected recurrent carotid stenosis or occlusion were asymptomatic or manifest by transient cerebral ischemia. Therefore RpCEADS cannot be justified as a means of preventing late strokes related to recurrent stenosis. PMID- 1460722 TI - Congress to simplify those complex, anxiety-provoking immunization booklets. PMID- 1460723 TI - Marfan syndrome, hypertrophic cardiomyopathy findings underline avoidance of some sports. PMID- 1460724 TI - Science organization sponsors discussions about what constitutes health care reform. PMID- 1460725 TI - From the Food and Drug Administration. PMID- 1460726 TI - From the Centers for Disease Control and Prevention. Trends in years of potential life lost before age 65 among whites and blacks--1979-1989. PMID- 1460727 TI - The National Practitioner Data Bank: bane or benefit? PMID- 1460728 TI - Outpatient anterior cruciate ligament reconstruction and patient-controlled analgesia. PMID- 1460729 TI - Pulmonary toxicity of amiodarone. PMID- 1460730 TI - Providers? PMID- 1460731 TI - Estimates of physician joint ventures. PMID- 1460732 TI - If called by the insurance company, call in the patient on the call. PMID- 1460733 TI - The influence of age and sex on asthma admissions. AB - OBJECTIVE: To describe demographic data from a large population of asthmatic patients to define the role of age and sex as risk factors for asthma admission. DESIGN: A retrospective review of all asthma admissions as defined by International Classification of Diseases, Ninth Revision, code 493.0. SOURCE: All medical-surgical admissions from 67 hospitals in five counties of southeastern Pennsylvania from 1986 through 1989. RESULTS: Patients admitted for asthma treatment (33,269) were reviewed. In the 0- to 5-year-old and 6- to 10-year-old age groups, males were admitted nearly twice as often as age-identical females. In the 11- to 20-year-old age group, admissions for males and females were nearly identical. Between 20 and 50 years of age, the female-to-male ratio was nearly 3:1. Thereafter, females were admitted for asthma at a rate of about 2.5:1 when compared with their age-equivalent male counterparts. Length of stay increased proportionally as the patient age increased. After 30 years of age, the length of stay was slightly greater for females than males. CONCLUSIONS: There is a much higher rate of admission for prepubertal males than females. However, there is a higher incidence of asthma admissions for adult females than adult male asthmatic patients, and female asthmatic patients experience longer hospital stays per admission as well. These data indicate that adult females are more severely affected by asthma and raise the possibility that hormonal or biochemical differences related to sex may play a role in the pathophysiology of asthma. PMID- 1460734 TI - Antidepressant medications and the relative risk of suicide attempt and suicide. AB - OBJECTIVE: Suicide by drug overdose is a major public health problem, and antidepressant medications are the most common agent involved. European studies suggest differences in the rates of suicide by overdose among antidepressants, but no reports have been published for the United States. We estimated the comparative risks of suicide attempts and suicides, and the relative risk of fatality in the event of an overdose for the major antidepressants currently marketed in the United States. DATA SOURCES: Information regarding suicide attempts and suicides by antidepressant overdose was obtained from the published reports of the Drug Abuse and Warning Network and the annual report of the American Association of Poison Control Centers, and corrected for differences in total annual prescriptions using data from the National Prescription Audit. RESULTS: The risk of a suicide attempt did not appear to differ among antidepressants. The tricyclic antidepressants were associated with a higher rate of death in the event of an overdose than the newer nontricyclic antidepressants in both the annual report of the American Association of Poison Control Centers and the Drug Abuse and Warning Network data. The chance of death after an overdose was greater for desipramine hydrochloride than for other tricyclics. CONCLUSION: The higher risk of suicide with tricyclics vs nontricyclics may be explained by a higher rate of death from overdose rather than more suicide attempts. Tricyclics carry the risk of greater cardiotoxicity. The basis for the even higher rate of death/overdose of desipramine is not known and requires further research. If these findings are replicated in a case-control study design, they have important implications for the choice of an antidepressant for the depressed patient at risk for suicidal behavior. PMID- 1460735 TI - Toward an epidemiology and natural history of SIRS (systemic inflammatory response syndrome) AB - BACKGROUND: New definitions for sepsis and the systemic inflammatory response syndrome (SIRS) have been established. Comparatively little is known, however, about the types of patients who will be included within these new definitions. OBJECTIVES: To determine what is--and what is not--known about the epidemiology and natural history of severe sepsis and SIRS. DESIGN: A comparative analysis of patient characteristics in the Methylprednisolone, Veterans Administration Systemic Sepsis, HA-1A, and E5 studies. RESULTS: At least 15% of patients in these studies had no documented infection; the proportion of all patients with severe SIRS and no documented infection is probably higher. Even among patients with presumed infection, less than half had bacteremia, and only about half had gram-negative infection or shock. The difference in the mean mortality rate of the combined studies at 14 days was 26%, while at 1 month it was 42%. Gram negative sepsis and gram-positive sepsis seem to have similar mortality rates. Whether shock increases 30-day mortality is unclear. CONCLUSIONS: Patients with severe SIRS should not be assumed to have gram-negative infection; furthermore, data derived from studies of patients with gram-negative infection should be applied cautiously to all patients with SIRS. Studies of patients with sepsis or SIRS should include at least a 1-month follow-up if mortality is an end point. More consistent definitions of these disorders should permit more effective comparisons across studies. PMID- 1460736 TI - Estimates of the number of motherless youth orphaned by AIDS in the United States. AB - OBJECTIVE: To estimate the number of youth in the United States who have been or will be left motherless by the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic, in order to project the need for family supports, age-appropriate foster and congregate care, and mental health and social services. DESIGN: Orphans are defined as youth whose mothers (the usual caregiving parent) die of HIV/AIDS-related causes. A mathematical model was constructed to estimate the number of such motherless youth. Cumulative fertility rates were applied to the number of reported AIDS deaths (1981 through 1990) and projected deaths (1991 through 1995) of adult women less than 50 years old. The results were adjusted for underreporting of HIV/AIDS-related mortality, pediatric AIDS deaths, infant mortality, ethnic and racial variation in fertility, and decreased fertility associated with late-stage HIV disease. Estimates were made for the number who were children (less than 13 years of age), adolescents (13 to 17 years of age), or young adults (18 years of age or older) at the time of their mothers' death. RESULTS: By the end of 1995, maternal deaths caused by the HIV/AIDS epidemic will have orphaned an estimated 24,600 children and 21,000 adolescents in the United States; unless the course of the epidemic changes dramatically, by the year 2000, the overall number of motherless children and adolescents will exceed 80,000. In 1991, an estimated 13% of US children and 9% of adolescents whose mothers died of all causes were children of women who died of HIV/AIDS-related diseases. These proportions will surpass 17% and 12%, respectively, by 1995. The vast majority of these motherless youth will come from poor communities of color. CONCLUSIONS: A large and rapidly growing number of American youth are being orphaned by the HIV/AIDS epidemic. Unless increased attention and resources are devoted to this vulnerable population, a social catastrophe is unavoidable. PMID- 1460737 TI - Risk of fatal and near-fatal asthma in relation to inhaled corticosteroid use. AB - OBJECTIVE: To examine the relationship between patterns of use of inhaled beclomethasone dipropionate and the risk of fatal and near-fatal asthma. DESIGN: Nested case-control analysis of a historical cohort; a further analysis. SETTING: The 12,301 residents of Saskatchewan aged 5 to 54 years who were dispensed 10 or more asthma drugs from 1978 to 1987. PATIENTS: The 129 persons who experienced asthma death (n = 44) and near-death (n = 85) and their 655 controls matched as to age and date of entry into the cohort, with the additional matching criteria of at least one hospitalization for asthma in the prior 2 years, region of residence, and having received social assistance. MAIN OUTCOME: Life-threatening attacks of asthma defined as death due to asthma or the occurrence of hypercarbia, intubation, and mechanical ventilation during an acute attack of asthma. RESULTS: After accounting for the risk associated with use of other medications and adjustment for markers of risk of adverse events related to asthma, subjects who had been dispensed, on average, one or more metered-dose inhalers of beclomethasone per month over a 1-year period had a significantly lower risk of fatal and near-fatal asthma (odds ratio, 0.1; 95% confidence interval, 0.02 to 0.6). CONCLUSION: These data support recent guidelines from several countries that recommend the use of inhaled corticosteroids in moderate and severe asthma. PMID- 1460738 TI - Clinical ecology. Council on Scientific Affairs, American Medical Association. PMID- 1460739 TI - The impact of health insurance reform on the law governing the physician-patient relationship. PMID- 1460740 TI - Uninsured children and national health reform. PMID- 1460741 TI - The 'silent' legacy of AIDS. Children who survive their parents and siblings. PMID- 1460742 TI - A piece of my mind. Another language. PMID- 1460743 TI - Neuropsychiatric assessment of orphans in one Romanian orphanage for 'unsalvageables'. PMID- 1460744 TI - [Effects of propentofylline (HWA285) on recovery of brain function following total cerebral ischemia (TCI) in dogs]. AB - We examined the effects of a xanthine derivative, propentofylline, on recovery of brain function following TCI in 23 adult mongrel dogs. TCI was produced by clamping ascending aorta with aortoatrial bypass formation. The dogs were divided into 3 groups: preischemic administration (0.3 mg.kg-1.min-1, 30 min), post ischemic administration (0.5 mg.kg-1.min-1, 6h) and control. The progress of recovery of EEG, respiration, reflexes, motor functions, arousal state and behavior were observed for 7 days after TCI and the latter 5 functions were analysed using neurologic deficit score (NDS). Propentofylline shortened the time necessary for reappearance of EEG after the starting of recirculation but could not improve the NDS. PMID- 1460745 TI - [Clinical examination of acetated Ringer solution in patients with normal liver function and those with liver dysfunction]. AB - Acetated Ringer solution (AR) was studied clinically to find its usefulness in patients with liver dysfunction compared with lactated Ringer solution (LR). The thirty-eight patients scheduled to be operated were divided into four groups (Group I: with normal liver function and AR infused, Group II: with normal liver function and LR infused, Group III: with liver dysfunction and AR infused, Group IV: with liver dysfunction and LR infused). AR or LR was administered to each group at a speed of 10 ml.kg-1.h-1, and we investigated the differences of these four groups clinically. L-lactic acid increased significantly in all groups after administration of AR or LR. D-lactic acid increased in LR groups, and acetic acid increased in AR groups. However, the other parameters, including the acid-base balance, electrolytes and liver function, showed no significant changes in any group. Therefore the status of liver dysfunction did not affect the metabolism of lactic acid in this study. These findings indicate that as an intraoperative fluid, AR is just as useful as LR. However, there was no significant difference between the data of AR groups compared with those of LR groups. In conclusion, AR is not necessarily a better fluid compared with LR as an intraoperative fluid in patients with liver dysfunction. PMID- 1460746 TI - [Influence of normovolemic hemodilution on organ blood flow]. AB - The normovolemic hemodilution was carried out in adult mongrel dogs by using SALIN-HES, and organ blood flow was measured by hydrogen clearance method, and the distribution rate of cardiac output to the organ was calculated. The organ blood flow was measured in the cerebral cortex (CCBF), liver (LBF) and renal cortex (RCBF). The hematocrit level before hemodilution was 42%. The subsequent hematocrit levels (at 4 stages) were 26% at S1, 18% at S2, 10% at S3 and 5% at S4. The results suggest that higher the degree of hemodilution, CCBF increases more, and that CCBF increased significantly from S2 to S4. However, no significant variation was observed in the distribution rates of the blood flow. Moreover, no significant variation by hemodilution was also observed in both LBF and RCBF. However, a significant decrease of the distribution rate of the blood flow was observed in LBF from S1 to S2 and RCBF from S2 to S4, and the higher the degree of the hemodilution is, the rate of blood flow decreased the more remarkably. PMID- 1460747 TI - [Coagulation changes during liver resection]. AB - Thrombin-antithrombin III complex (TAT) and plasminogen activator inhibitor (PAI) were measured during liver resection surgery in 8 patients. TAT and PAI activities of patients under liver resection were compared with those of 11 patients under resection of esophageal carcinoma. TAT activity increased during liver resection (P < 0.001) and reached 14 times (P < 0.001) of its control value in the recovery room. PAI activity was very stable during operation, but increased to twice (P < 0.01) of its control value in the recovery room. TAT activity of patients after liver surgery in the recovery room was (P < 0.05) more than twice of that of patients after esophageal surgery. We conclude that hypercoagulable state occurred during liver resection to a greater degree compared with that observed with esophageal surgery, and that its cause might be liver resection itself. PMID- 1460748 TI - [Effects of sevoflurane anesthesia on dopamine metabolism in the rat brain]. AB - To elucidate the mechanism of general anesthesia, effects of sevoflurane anesthesia on dopamine metabolism in rat brain were studied. Sevoflurane 3% was administered for 20 minutes to Wistar male rats weighing 230-270 g under spontaneous respiration. The rats were sacrificed by decapitation and the brains were rapidly removed. They were dissected into nine discrete regions, locus coeruleus, pons plus, medulla oblongata, hypothalamus, thalamus, basal ganglia, midbrain, hippocampus, amygdala and cerebral cortex. The contents of dopamine (DA) and its major metabolites, 3, 4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) were measured by high performance liquid chromatography with the dual-cell coulometric detector before anesthesia, 20 minutes after the start of anesthesia and at the recovery from anesthesia. Significant increases in DA levels were observed in the pons, hypothalamus, thalamus and amygdala by sevoflurane anesthesia as compared with the control group. DOPAC levels increased significantly in the pons, hypothalamus, basal ganglia and cerebral cortex at the recovery from anesthesia. A significant increase in HVA levels was observed in amygdala by sevoflurane anesthesia, while an appreciable decrease in HVA levels was observed in hippocampus at recovery from anesthesia. It is concluded that DA metabolism is significantly suppressed in the pons, hypothalamus, thalamus, basal ganglia, midbrain and amygdala during sevoflurane anesthesia and this change in DA metabolism may be associated with the mechanism of sevoflurane anesthesia. PMID- 1460749 TI - [Effects of sevoflurane and isoflurane on intraocular pressure in adult patients]. AB - We investigated effects of two anesthetic agents, sevoflurane and isoflurane, on intraocular pressure (IOP). Forty adult patients were allocated randomly to two groups; Group S (sevoflurane) or Group I (isoflurane). All patients were given a bolus of thiamylal (4-5 mg.kg-1) and vecuronium (0.1-0.2 mg.kg-1) and maintained with 1-3% sevoflurane or isoflurane supplemented with nitrous oxide. Ventilation was controlled and ETCO2 was monitored. IOP, blood pressure and heart rate were measured before induction of anesthesia (control) and at the 7 points of 5, 10, 15, 30, 45, 60 and 120 minutes after intubation. In Group S, IOP was reduced significantly until 30 min compared with control IOP and the maximum decrease was 40% at 10 min. In Group I, IOP was consistently lower than control and the maximum decrease was 40% at the same time as in Group S. But there were no significant differences between the two groups at each point. It seems that the remarkable reductions of IOP after inductions are mainly caused by induction agents. In both groups, hemodynamic parameters showed no remarkable changes during maintenance. These results suggest that both sevoflurane and isoflurane are useful anesthetics for elderly patients receiving ophthalmic surgeries. PMID- 1460750 TI - [Effects of enflurane, isoflurane, and sevoflurane on renal tubular functions]. AB - Twenty-seven patients without renal disease were divided randomly into three groups of each nine patients. Each group received either enflurane, isoflurane or sevoflurane. The renal tubular functions were examined during anesthesia and on the first postoperative day. By inhalation of 1.49 MAC hours of enflurane, 2.17 MAC hours of isoflurane or 1.29 MAC hours of sevoflurane, creatinine clearance, Na excretion rate, urine beta 2-microglobulin and urine N-acetyl-beta-D glucosaminidase showed no significant changes during anesthesia and the during postoperative period among anesthetic agents used. These results indicate that enflurane, isoflurane or sevoflurane does not affect renal tubular function specifically under anesthesia when each was given for less than four hours. PMID- 1460751 TI - [Plasma catecholamine levels during air-oxygen-enflurane anesthesia compared with those during nitrous oxide-oxygen-enflurane anesthesia]. AB - This study was designed to investigate the differences in plasma levels of epinephrine, norepinephrine and dopamine during air-oxygen-enflurane anesthesia (AOE) and those during nitrous oxide-oxygen-enflurane anesthesia (GOE). These catecholamine levels were measured at 8 carefully defined points before and during hysterectomy or ovariectomy in two groups of each ten patients. Plasma levels of epinephrine decreased significantly immediately after intubation in both groups. In the AOE group, epinephrine levels increased significantly 30 and 60 minutes after the beginning of the operation. In the GOE group, however, epinephrine levels decreased significantly 15 and 30 minutes after the beginning of the operation. The difference between the two groups was statistically significant. Plasma levels of norepinephrine increased significantly after the beginning of the operation in the GOE group but no significant differences were found in the AOE group except the levels 60 minutes after the operation. The difference between the two groups was statistically significant 15 minutes after the operation. Plasma levels of dopamine remained unchanged in the two groups. Mean arterial pressure changed with intubation and surgical stress in the two groups. The arterial pressure was significantly higher 30 minutes after the operation in the GOE group compared with AOE group. Pulse rate increased significantly during anesthesia and surgery in the GOE group. It is concluded that AOE induces more increase of plasma epinephrine and less release of plasma norepinephrine compared with GOE. PMID- 1460752 TI - [The effect of epidural anesthesia on prostaglandin synthesis during alveolar hypoxia]. AB - The effect of epidural anesthesia on prostaglandin synthesis during alveolar hypoxia was investigated in 20 patients. Group I received intravenous anesthesia and group II received epidural and intravenous anesthesia. Patients in both groups were intubated with a double-lumen end tracheal tube, allowing separate ventilation of the right lung with 5% CO2, 6% O2 and 89% N2 as a hypoxic challenge and the left lung with 100% O2. In both groups, adequate systemic oxygenation was maintained. Pulmonary artery pressure and pulmonary vascular resistance increased significantly in both groups. Cardiac index decreased significantly in group II. Both 6-keto PGF1 alpha and thromboxane B2 increased in group I, but only 6-keto PGF1 alpha increased in group II. Hypoxic pulmonary vasoconstriction (HPV) stimulated prostaglandin synthesis. 6-keto PGF1 alpha is the major arachidonic acid metabolite released during HPV. The results suggest that epidural anesthesia does not inhibit HPV, but exerts some effects on thromboxane B2 synthesis during alveolar hypoxia. PMID- 1460753 TI - [Effect of halothane on the mechanical properties of rabbit right ventricular papillary muscle in the presence of either alpha or beta stimulant positive inotropic agent]. AB - The effects of halothane (1-3 MAC) on the isometric twitch tension, the contracture tension induced by 1 mM barium (Ba2+) in the rabbit right ventricular papillary muscles, and the transient tension response to step length change during barium contracture, were analyzed in the presence of either alpha (3 x 10( 5) M phenylephrine+10(-6) M bupranolol) or beta (10(-7) M isoproterenol) stimulants. The isometric twitch tension was significantly decreased with the administration of halothane dose dependently, in the presence of both alpha or beta stimulants. Both the time to peak (TP) and the time to half relaxation (THR) were remarkably shortened with the administration of halothane in the presence of both alpha or beta stimulants. The Ba2+ contracture tension was also decreased with the administration of halothane dose dependently in the presence of both alpha or beta stimulants. The tension transient became faster with the administration of halothane in the presence of the alpha stimulant, but not in the presence of the beta stimulant. These results suggest that halothane decreases the number of active crossbridges regardless of the inotropic states induced by the two different stimulants. Also on increase the rate of crossbridge kinetics occurs in the presence of the alpha stimulant but not in response to the beta stimulant. PMID- 1460754 TI - [Pharmacokinetics of ketamine and pentazocine during total intravenous anesthesia with droperidol, pentazocine and ketamine]. AB - Pharmacokinetics was studied in ten surgical patients who underwent various operative procedures of about 4 hours under total intravenous anesthesia with droperidol, pentazocine and ketamine (DPK). Plasma levels of ketamine, its metabolites and pentazocine were determined thirteen times during and after DPK. During anesthesia, ketamine (KO) and norketamine (KMI) levels ranged from 0.7 to 1.0 micrograms.ml-1 and from 0.09 to 0.74 micrograms.ml-1, respectively. A small amount of dehydronorketamine (KM II) was detected only 90 min after the start of DPK anesthesia. Plasma half-lives of ketamine were calculated to be 33 min for distribution phase (alpha phase) and 60 min for elimination phase (beta phase), respectively. Pentazocine levels decreased 300 min after the induction of DPK to 10% of the control level measured 5 min after its injection. Plasma half-lives of pentazocine were 60 min for alpha phase and 140 min for beta phase, respectively. The data obtained in this clinical study show that pharmacokinetics of ketamine during DPK is almost similar to that of DFK. PMID- 1460755 TI - [Interdependence of preload, afterload and contractility: their relation to cardiac function curve]. AB - Formerly, the major determinants of cardiac performance, i.e., preload, afterload contractility, and heart rate had been considered independent. This individual concept of these determinants was originally advocated by E.H. Sonnenblick in 1960's, providing an extremely useful tool in understanding basic cardiac mechanical physiology. We now know, however, that these determinants of cardiac performance are, in fact, interdependent with each other both at cellular and at ventricular levels. This concept of the interdependency of the determinants, in turn, is of practical importance during the conduct of clinical anesthesia. Since we cannot isolate one determinant from the other, we have to deal with them as they are. Furthermore, monitoring a parameter of one aspects of the patient's cardiac performance is not sufficient to understand or estimate patient's status. It is necessary to integrate these informations to make clinical decision under uncertain situations. PMID- 1460756 TI - [A patient with severe ventricular tachycardia who was saved by prolonged extracorporeal lung and heart assist]. AB - A 47-y-o man had been suffering from cardiac failure due to refractory ventricular tachycardia (VT) after myocardial infarction. He underwent resection of the left ventricular aneurysm and cryocoagulation of the arrhythmogenic foci. On the 2nd post-operative day, VT often recurred in spite of repeated cardioversion and drug therapy, and threatened his life, even under IABP. Therefore, a veno-arterial bypass route was made and extracorporeal lung and heart assist, ECLHA, was started with a heparin bonded Maxima lung on the following day. Even under ECLHA, VT continued to recur. Cryocoagulation of the VT foci was tried again, without immediate success. A record high dose of beta blockers, given under the circulatory support by ECLHA, stopped VT on the following day. The patient was weaned from the ECLHA circuit 12 days after the first operation, then from IABP on the 14th day. During the 10 day course of surgeries and ECLHA, the patient had almost 100 defibrillations. But for ECLHA, we may say that the patient couldn't have survived two open heart surgeries, administration of a great amount of beta-blockers, and repeated cardiac arrest without neurological sequelae. PMID- 1460757 TI - [Anesthetic management of an infant with a single ventricle (asplenia syndrome) for non-cardiac surgery]. AB - Ketamine and fentanyl were used for surgery of esophageal hiatus hernia in a 9 month old boy with single ventricle (asplenia syndrome). The patient was orally premedicated with diazepam 2.5 mg, and intravenously with atropine 0.04 mg. General anesthesia was induced with ketamine-fentanyl-pancuronium-100% oxygen, and maintained with fentanyl-pancuronium-100% oxygen. The total dose of ketamine or fentanyl was 0.8 mg.kg-1 or 15 micrograms.kg-1, respectively. Systolic blood pressure and heart rate of the patient were stable during ketamine-fentanyl anesthesia. Arterial oxygen saturation measured by pulse oximetry was over 90% and arterial oxygen tension was above 60 mmHg during the operation. Ketamine fentanyl anesthesia might be useful for non-cardiac surgery of a child with cyanotic congenital heart disease. PMID- 1460758 TI - [A case of bronchospasm during induction of isoflurane anesthesia]. AB - Isoflurane is generally considered to prevent increase in bronchomotor tone. We report a case of bronchospasm associated with exposure to isoflurane. A 11-year old girl was scheduled for tonsillectomy because of repeated fever. Anesthesia was induced with nitrous oxide, oxygen and sevoflurane. Sevoflurane was switched to isoflurane and increased gradually to 3%. Shortly after inhalation of isoflurane, eruption at chest appeared and auscultation of the chest revealed dry rale. Aminophylline and hydrocortisone were injected and isoflurane was discontinued. Ventilation with sevoflurane was started, but there was no improvement. Intramuscular epinephrine was given and sevoflurane was discontinued. After this, the wheezing improved. Four days later she underwent tonsillectomy under sevoflurane anesthesia uneventfully. PMID- 1460759 TI - [A case of postoperative hepatic injury after sevoflurane anesthesia]. AB - A 63 year old man underwent MCA aneurysmal neck clipping under O2-N2O-enflurane anesthesia. On the 46th postoperative day after the first operation, he had cranioplasty under O2-N2O-sevoflurane anesthesia. Hepatic injury occurred after the operation, and GOT, GPT and bilirubin increased above 700 IU.l-1, 800 IU.l-1 and 15.0 mg.dl-1 respectively but consciousness disturbance, hyperammonemia and DIC did not appear. His hepatic injury improved on conservative therapy. It seems that his hepatic injury was not caused by hepatitis viruses or hepatotoxicity of any drugs, but caused by cross sensitization between halogenated inhalation anesthetics, especially enflurane and sevoflurane, judging from drug induced lymphocyte stimulating test (DLST). We have to select an anesthetic method considering potential hepatic injury by halogenated anesthetics in a case of repeated anesthesia and operations during a short-term. PMID- 1460760 TI - [The effects of pentazocine, diazepam and midazolam in patients to reduce the uncomfortable feeling during epidural block procedure]. AB - The effects of pentazocine, diazepam and midazolam in 100 patients to reduce the uncomfortable feeling during epidural block procedure were studied. All patients (ASA I-II) were premedicated with intramuscular atropine sulfate 0.5 mg and hydroxyzine 50 mg. To relieve pain and anxiety during epidural block procedure, pentazocine (15 mg; 20 Cases or 30 mg; 20 Cases), diazepam (5 mg; 20 Cases) or midazolam (2.5 mg; 20 Cases) was given intravenously in the operating room before epidural procedure. After the epidural block, patients were anesthetized with nitrous oxide-oxygen-isoflurane or nitrous oxide-oxygen-sevoflurane. The following day, patients' self-assessments of pain during epidural block procedure were categorized as good and fair. The effects of drugs were compared between patients with im premedication only with patients with further iv administration. Patients with pentazocine 15 mg were similar to the patients given only im premedication. Pentazocine 30 mg and diazepam 5 mg tended to allay the patients' pain feeling. Midazolam 2.5 mg was effective producing anterograde amnesia and antianxiety effects. Small doses of midazolam were effective to relief patients' uncomfortable feeling. PMID- 1460761 TI - [Polarized light irradiation near the stellate ganglion in a patient with Raynaud's sign]. AB - Polarized light irradiation near the stellate ganglion was performed in a 55-year old female with Raynaud's sign. She was suffering from cold and numb pain in bilateral fingers for 1 year. Stellate ganglion block and low reactive-level laser therapy near the stellate ganglion were not sufficient to relieve this symptom. Polarized light irradiation near the stellate ganglion induced a sting stimulation and warm sensation in her hands. Thermograms revealed a remarkable increase in temperature of her hands. The results imply that polarized light irradiation near the stellate ganglion increases blood flow of forearms and relieves Raynaud's sign. PMID- 1460762 TI - [Hemodynamic management of LOS using prolonged VA bypass circulatory assist]. AB - The authors managed five LOS patients using prolonged V-A bypass circulatory assist. Maximum CVP values were under 12 mmHg in three survivors, and 17 mmHg and 20 mmHg in two nonsurvivors. Maximum PCWP values were under 14 mmHg in survivors, and 19 mmHg and 20 mmHg in nonsurvivors. Dopamine was administrated in all cases and norepinephrine was administrated at a rate of less than 0.3 microgram.kg 1.min-1 in survivors, and in two nonsurvivors, norepinephrine was used at a rate of 0.36 and 1.2 micrograms.kg-1.min-1. Before and after disconnection of V-A bypass, the bypass flow of the three survivors were under 1.0 l.min-1 just before disconnection, and immediately after it, the preload did not increase, and the dose of administrated catecholamine increased. V-A bypass time intervals of the three survivors were 71, 42 and 87 hours, and those of the two nonsurvivors were 71 and 43 hours. Maximum bypass flow rate was above 40ml.kg-1.min-1 in four of five patients. The authors discussed the management of the patients' heart and of the V-A bypass machine during the prolonged V-A bypass circulatory assist. PMID- 1460763 TI - [The epidemiology and clinical features of anaphylactic and anaphylactoid reactions in the perioperative period in Japan: a survey with a questionnaire of 529 hospitals approved by Japan Society of Anesthesiology]. AB - In an attempt to review the Japanese epidemiology of the anaphylactic and/or anaphylactoid reactions in the perioperative period, we surveyed 529 hospitals approved by Japan Society of Anesthesiology with a questionnaire about drug induced immediate adverse reactions. Recovery rate of questionnaires was 15% (80 hospitals in 529 hospitals), and 28 cases of anaphylaxis or anaphylactoid reaction were reported. Most patients were in their teens and twenties. Male were 10, and female were 12 (unknown gender; 6). Reaction occurred during the induction of anesthesia in 28.6% of the patients, and during the maintenance of anesthesia in 67.9%. Seventy-five percent of the patients had no past history of drug-induced allergy nor tendencies of atopy. Most frequent clinical signs were cardiovascular (85.7%) and cutaneous (100%) manifestations. Respiratory signs appeared in 42.9% of the patients. Patients were frequently unconscious and covered with drapes, and there is a potentially danger of masking early signs and symptoms of anaphylaxis. In most of the patients, cardiovascular collapse appeared as the first noticeable sign. Causative drugs were confirmed only immunologically in one patient. In other cases causative drugs were presumed based on clinical courses. Anaphylaxis and anaphylactoid reaction are important causes of morbidity and mortality. The incidence in Japan was 0.01% (1:10,000) and the mortality was 4.76%. PMID- 1460764 TI - [Establishment and characterization of a new poorly differentiated gastric cancer cell line (MKK-1), derived from Borrmann type 3 tumor]. AB - A new human gastric cancer cell line (MKK-1), derived from Borrmann type 3 tumor of the stomach, was established. It was obtained from poorly differentiated adenocarcinoma. The cell line grew in vitro, forming a sheet of monolayered cells and attaching firmly to the inner surface of culture vessels; it continued to grow for more than 1 year and 4 months. Its doubling time was 12.6 hours, with a chromosomal mode of 69. The cells could grow in nude mice; histological findings of the tumors developed in the mice showed a pattern similar to those in the primary tumor, i.e., poorly differentiated adenocarcinoma. With regards to tumor related antigens, production of the CA19-9 was observed as time-dependent increase and was detected at a level of 4 U/ml in the culture supernatant on passage day 7, showing high values compared with the control. Immunostaining was positive for both the anti CEA antibody and the anti CA19-9 antibody. In sera examined in week 4 after subcutaneous transplantation of MKK-1 to the nude mice, CEA and CA19-9 levels were high, at 8.93 ng/ml and 44 U/ml, respectively. There was a positive correlation between increase in a tumor weight and the production of tumor-related antigens. PMID- 1460765 TI - [Hypolactasia in Japanese Crohn's patients]. AB - 20 g lactose load test, BHT and LTT done simultaneously were examined in 32 Crohn's disease patients and 51 healthy volunteers. Hypolactasia frequency were examined. A rise in hydrogen concentration > 20 parts per million (ppm) above the base line during breath hydrogen test and maximum blood sugar rise during lactose tolerance test were considered to indicated Hypolactasia. High rates, 50% by BHT and 72.5% by LTT, of primary adult hypolactasia were found in healthy volunteers as previously reported. Higher rates, 83.3% by BHT and by LTT (p < 0.05), were observed in Crohn's disease patients. There were higher rates in small intestine type Crohn's disease (91.6% by BHT, 92.3% by LTT) compare with healthy volunteers but no difference were found with large intestine type Crohn's disease. PMID- 1460766 TI - [Immunohistochemical study of proliferative cells in colorectal adenoma and carcinoma]. AB - The distribution of proliferating cells was studied in colorectal carcinoma by immunohistochemistry using monoclonal antibody-DNA polymerase alpha and Ki-67. Colorectal carcinoma was classified into two types by growth mode: (1) intramucosal polypoid growth carcinoma and (2) non-polypoid growth carcinoma. The labeling index of anti-DNA polymerase alpha and Ki-67 in non-polypoid growth carcinoma was significantly higher than in polypoid growth carcinoma. The labeling index of polypoid growth carcinoma was significantly higher than adenoma. The proliferating cells in polypoid growth carcinoma and adenoma were mainly distributed in the upper third of intramucosal neoplastic gland. However, in non-polypoid growth carcinoma, the proliferating cells of intramucosal lesion were scattered mainly in the lower third along the neoplastic gland. The distribution pattern of proliferating cells in early carcinoma with non-polypoid growth were similar to those of non-polypoid growth advanced carcinoma. These results suggested that submucosal invasion occurred more rapidly in intramucosal non-polypoid growth carcinoma. PMID- 1460767 TI - [Purification and culture of mouse gallbladder epithelial cells in secondary culture using microexplant culture on collagen gel]. AB - We established a new method of purification and culture of mouse gallbladder epithelial cells. In primary culture, mouse gallbladder tissue was cultured on collagen gel using microexplant culture method; the epithelial cells spread in a single sheet from the microexplant toward the periphery on the collagen gel. Tiny fragment of the collagen gel containing the border of epithelial cell layer was retransplanted onto the another collagen gel for secondary culture. This retransplantation allowed the proliferation of the epithelial cells without mesenchymal contamination, which spread on the collagen gel at the rate of 0.29 +/- 0.06 mm per day for more than two weeks. The cultured epithelial cells showed cuboid or columnar shape with focal mucus production, which is morphologically and functionally similar to the in vivo epithelial cells. This suggests that this in vitro culture method can be used to pathophysiological studies of biliary epithelial cells as well as for the method of purification of the epithelial cells. PMID- 1460768 TI - [A case report of abdominal congenital esophageal cyst in adult]. PMID- 1460769 TI - [A case report of eosinophilic gastroenteritis with CT findings]. PMID- 1460770 TI - [A case of ulcerative colitis with localised giant inflammatory polyposis]. PMID- 1460771 TI - [A case of HBV carrier with acute hepatitis type B developed after initial infection in adulthood]. PMID- 1460772 TI - [A case of chronic hepatitis C with primary hypothyroidism manifested during interferon treatment]. PMID- 1460773 TI - [A case of mucinous cystadenoma in the tail of the pancreas accompanied with tubular adenocarcinoma in the head]. PMID- 1460774 TI - [A case of squamous cell carcinoma of the pancreas with prominent extrapancreatic growth]. PMID- 1460775 TI - [Five year follow-up study on dementia in institutions for the elderly]. AB - The purpose of this study was to clarify the prognosis of senile dementia based on a 5-year follow-up study in institutions for the elderly. The subjects consisted of 747 cases over 60 years of age. Of these 316 cases showed clinical dementia but 431 cases had no intellectual disturbance in July, 1987. The mortality rate (56.3%) of the demented group was significantly higher than that (31.8%) of the non-demented group. The mortality rate of patients increased with aging. However, the mortality rate of the demented group did not correlate with the severity of dementia. An autopsy study revealed that the direct causes of death in 51.1% of demented patients were pneumonia and cardiovascular diseases. Among the demented patients followed up for 5 years, 22.5% showed severe worsening of dementia, 25.8% showed slight or moderate degree of worsening and 51.7% showed no change. Factors causing exacerbation of dementia included cerebrovascular disease and bone fracture. PMID- 1460776 TI - [Effect of chronic smoking on regional cerebral blood flow in asymptomatic individuals]. AB - The chronic effects of cigarette smoking upon regional cerebral blood flow (rCBF) are unclear. The present study investigated the effects of smoking on rCBF assessed by intravenous 133Xe injection in 40 asymptomatic individuals. Analysis was performed using linear regression analysis and multiple regression analysis, creating a model of the rCBF as a function of cerebrovascular risk factor. The risk factors included smoking status, smoking index, age, gender, mean arterial blood pressure, total cholesterol, fasting blood glucose, hematocrit and STT change and left ventricular hypertrophy in electrocardiogram. The male-to-female ratio was higher in the smoking group (18/2) than that in the non-smoking group (2/18). Among the smokers, mean hematocrit was significantly higher than in the non-smokers (p < 0.01). There was no significant difference in rCBF and other variables between the two groups. Linear regression analysis revealed significantly negative correlations between smoking index and CBF in the whole brain (r = -0.33; p < 0.05), right hemisphere (r = -0.34; p < 0.05), right parietal cortex (r = -0.36; p < 0.05), right occipital cortex (r = -0.34; p < 0.05) and left parietal cortex (r = -0.33; p < 0.05). In other variables, age, male sex, hematocrit, left ventricular hypertrophy and STT change showed significantly negative correlations with rCBF. To reduce the effect of confounding variables in our assessment of the dose-related response, a multivariate regression analysis was carried out treating rCBF as a dependent variable and risk factors as independent variables. In the final model, age, hematocrit, male sex and presence of BCG changes remained as independent negative predictors for rCBF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460777 TI - [An ultrasonic study of the relationship between extracranial carotid atherosclerosis and ischemic cerebrovascular disease in Japanese]. AB - The study is to evaluate the relationship between extracranial carotid atherosclerosis and ischemic cerebrovascular disease using noninvasive B-mode ultrasonography and X-ray computed tomography. The sensitivity of bruits for diagnosing severe carotid stenosis was also evaluated. A total of 229 consecutive Japanese patients were recruited for this study, of which 97 had chronic-stage ischemic cerebrovascular disease and remaining 132 patients had at least one risk factor for atherosclerosis. Carotid atherosclerosis was evaluated by B-mode ultrasonography. Ischemic cerebrovascular disease was assessed by history taking, neurological findings and X-ray CT examination. The severity of carotid atherosclerosis was assessed by using two indices; plaque score and maximum percentage diameter stenosis. We also evaluated whether it was ulcerated plaque or not. Plaque score was computed by summing up all carotid plaque thicknesses (mm) on both sides. According to the CT findings, cerebral infarction was divided into two types; deep subcortical infarction and cortical infarction. The incidence of cerebral infarction increased in relation to plaque score and maximum percentage stenosis. Although the incidence of cerebral infarction in patients without carotid atherosclerosis was only 33% (38/116), it in patients with moderate carotid atherosclerosis (plaque score > 5) was 59% (26/44) (p < 0.05, chi-square test). The incidence of ipsilateral infarction was revealed to be higher in patients with severe (50% or more) carotid stenosis (61%) than in cases of mild stenosis (28%) (p < 0.05). Thirteen patients had ulcerated plaques and they suffered more frequently cerebral infarction than patients without ulcerated lesions. Cortical infarction was more frequent in patients with severe carotid stenosis than in patients without carotid atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460778 TI - [Clinicopathological study of autopsy cases of pancreatic carcinoma in the elderly]. AB - A total of 257 autopsy cases of pancreatic carcinoma, including 160 male and 97 female cases with an average age of 68.2 years, were divided into an aged group (70 years or older, 136 cases) and a control group (younger than 70 years, 121 cases), and their respective clinicopathological features were compared. The male to female ratio was 1.2:1 in the aged group and 2.6:1 in the control group. In both groups, abdominal pain was noted in about one-third of the cases as the primary symptom, followed by appetite loss and icterus. Concerning the primary symptoms, the two groups did not differ from each other. The rate of surgical resection was higher in the control group (24.0%) than the aged group (10.3%). Mean survival times were similar in both groups (5.71 months for the aged group and 6.01 for the control group). Intrapancreatic location of the tumor showed similar tendencies in both groups. However, cancer of the head of the pancreas was 2.3 times more common than body/tail cancer in cases aged 80 or more. Approximately 90% of the cases were diagnosed as ductal carcinoma by histological examination. The degree of differentiation was similar in both groups, but the well differentiated type was somewhat predominant in cases 80 years or older. Metastasis or direct invasion was noted to the liver, peritoneum and lung in this order in both groups. Liver and lymph node metastasis were less frequent in cases 80 years or older. Multiple primary cancers were noted in 8.8% of the aged group and 9.1% of the control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460779 TI - [Quality of the life in hypertensive outpatients]. AB - In order to evaluate the quality of life (QOL) in hypertensive outpatients, we selected 78 patients with hypertension of various degrees of severity (WHO Classification I: 29 cases, II: 15, III: 34), 59 not ill healthy persons (N1) and 22 normotensive outpatients (N2) aged at 50 years and over, using the self completed questionnaire (QUIK) which we developed. QUIK covers four domains including physical functioning (20 questions), emotional adjustment (10), interpersonal relationships (10) and attitudes toward life (10) totaling 50 questions. In this study the internal consistency of QUIK was alpha = 0.95 by the Kuder-Richardson formula 20 and it's repeatability was r = 0.89 by the Spearman Brown formula. The QOL in hypertensive outpatients was definitely worse in terms of total score (N1 5.1 +/- 4.4 vs WHO II 9.3 +/- 7.2 and III 12.1 +/- 5.6, p < 0.05), for physical functioning (N1 2.5 +/- 2.1 vs WHO I 3.7 +/- 2.8, II 4.7 +/- 3.8, III 5.4 +/- 2.8 p < 0.05), for emotional adjustment (N1 1.2 +/- 1.4 vs WHO III 2.3 +/- 1.7, p < 0.01), for interpersonal relationships (N1 0.8 +/- 1.3 vs WHO III 1.6 +/- 1.5, p < 0.01) and for attitudes toward life (N1 0.7 +/- 1.2 vs WHO III 2.7 +/- 2.0 p < 0.01). The total QUIK score increased according to the severity of symptoms (WHO I 5.8 +/- 4.4, WHO II 9.3 +/- 7.2 and WHO III 12.1 +/- 5.6), respectively. The total score of WHO I was significantly lower compared with that of WHO III (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460780 TI - [Stomal stenosis following gastrectomy in the elderly]. AB - Seven hundred and thirty seven patients over 65 years of age (mean 76 years) undergoing gastrectomies from 1979 to 1991 were reviewed to evaluate the cause of stomal stenosis in the early postoperative period. Fifty seven (7.7%) patients, 24 males (5.6%) and 33 females (10.6%), had overt stomal stenosis or obstruction documented by radiological and endoscopic findings. The incidence of stenosis in females was significantly higher than in males (p < 0.05). Complications developed in 19 (20.0%) of 95 patients after gastroduodenostomy (Billroth-I), 29 (6.2%) of 465 after gastrojejunostomy (Billroth-II and others) and 8 (5.0%) of 159 after esophagojejunostomy (total gastrectomy). The incidence of complications in the first was significantly higher than in the other two (p < 0.01). The cause of stomal stenosis was classified into three groups; (1) transient stenosis due to stomal edema in 21 patients, (2) intestinal obstruction immediately adjacent to the stoma (kinking, invagination and volvulus) in 22, (3) organic stenosis of pathological origin (stomal ulcer, anastomotic leakage and strangulation by the proliferated mesocolon) in 14. The period of recovery from postgastrectomy retention was different in each group. It was 20.7 (mean) +/- 7.7 (SD) days in group (1), 29.7 +/- 12.6 days in group (2) and 62.1 +/- 30.0 days in group (3). These mean periods were significantly different from each other (p < 0.01). Group (1) and most of group (2) responded well to conservative management consisting of decompression by nasogastric suction and parenteral feeding but a reoperation was necessary for only two patients in group (2). Half of group (3) was treated by endoscopic dilatation and one third by reoperation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460781 TI - [EEG findings in hip fracture of the elderly]. AB - Twenty three patients with hip fractures, over 70 years old of age, who had surgical treatment and medical rehabilitation in the Yokufukai Geriatric Hospital were studied to evaluate changes of EEG findings at the time of hip fracture. In all cases, the pre-fracture ambulation status were independent. EEG findings were graded as normal, abnormal (minor degree, moderate-to-severe degree) and states of ambulation after hip fracture were graded good or poor. Good ambulation was defined as total independence and poor ambulation was defined as dependent on assistance or bedridden. In 11 cases of good ambulation, nine had an EEG which was normal or abnormal to a minor degree during pre- and post-fracture periods. In 12 cases of poor ambulation, seven had an EEG which was normal or abnormal to a minor degree in the pre-fracture period, but in the post-fracture period, only two of them were in the same grade and five showed moderate-to-severe abnormal EEG findings. Five out of 12 cases of poor ambulation demonstrated moderate-to severe EEG abnormality in pre- and post-fracture periods. The present study suggests that the response to hip fractures in the elderly are divided into two types based on their brain functions. One group can maintain good brain function immediately after hip fractures, while the other can not maintain sufficient brain function and lose their ambulatory ability. PMID- 1460782 TI - [A study on 24-hour ambulatory blood pressure in normotensive elderly, living in a local home for the aged]. AB - Ambulatory blood pressure (BP) was non-invasively monitored in 124 normotensive elderly, living in an old people's home at the annual health examination. Cases were divided into 41 cases < 75 years (group A, mean age 70.6) and 83 cases > or = 75 years (group B, 82.7) for analysis of the office BP and 24-hour BP. Whole day systolic BP in group B was significantly higher than those in the group A (p < 0.02) although no significant differences were observed in diastolic BP and pulse rate. Separated analysis of whole-day BP into daytime and nighttime revealed that the nighttime systolic BP in the group B was significantly higher than those in group A (132.2 +/- 17.4% vs. 123.8 +/- 18.6 mmHg, p < 0.02) whereas no significant difference was observed in day-time systolic BP between two groups (136.6 +/- 14.9 vs. 132.1 +/- 14.4 mmHg, n.s.). The day-night difference in systolic BP tended to be less in group B than in group A (4.5 +/- 11.6 vs. 8.2 +/ 12.2 mmHg, p < 0.10). The prevalence of non-dippers, who had a higher nighttime systolic BP than daytime systolic BP were 24.4% of the group A and 30.1% of the group B. It was concluded that systolic BP during the nighttime increased with the ageing process after age 60, although that during daytime did not change. PMID- 1460783 TI - [Serum alpha 1-antichymotrypsin in senile dementia]. AB - To evaluate the clinical significance of serum alpha 1-Antichymotrypsin (ACT) as an early diagnostic marker of senile dementia of Alzheimer type (SDAT), we measured 333 healthy and not demented elderly subjects, 27 cases SDAT and 25 cases of vascular dementia (VD). For the measurement, a new high-sensitivity method, double antibody radioimmunoassay method was developed. In healthy elderly subjects, the mean value of serum ACT was 0.229 mg/ml. A tendency towards increase of ACT with aging was noted but was not significant. The serum level of ACT in the SDAT patients was significantly higher (0.309 mg/ml) compared with the healthy elderly subjects and the VD patients (0.226 mg/ml) (p < 0.01). We concluded that in the patients with SDAT, there was an overproduction of ACT and the serum value of ACT was markedly elevated. The measurement of serum ACT is very useful (sensitivity = 88.9%, specificity = 68.7%; cut-off value = 0.250 mg/ml) for the early differential diagnosis of senile dementia. PMID- 1460784 TI - [A study of factors affecting the concentration of serum lipid peroxide in the elderly inhabitants in a rural area]. AB - Among 16 male (mean age of 66.6 years) and 51 female (mean age of 65.3 years) inhabitants of a rural area, the concentration of serum lipid peroxide measured as malondialdehyde (MDA) by Yagi's method was analyzed by physicochemical and food intake items. The MDA level in serum showed a peak of 6.2 nmol/ml at fifties years old in females and showed constant values of 4.6 and 6.1 nmol/ml for females and males, respectively, in those aged 60 more. The MDA level significantly correlated positively to total- or LDL-cholesterol level and urinary K/Cr, thus MDA level seemed to be a risk factor of arteriosclerosis. Fruit intake significantly positively correlated to MDA level in male. The MDA level showed a significantly higher level in the group with both higher total cholesterol and urinary K/Cr levels, than in the other groups. It is suggested that a high intake of potassium increases the MDA level in the group with higher total-cholesterol level. PMID- 1460785 TI - [A case of "pure" progressive autonomic failure in an elderly male]. AB - A 68-year-old man was admitted to our hospital because of postural hypotension in July 1991. He was also suffering from anhydrosis, urinary disturbances, constipation and impotence. He had not developed signs of Parkinsonism, cerebellar or peripheral neuropathy four years from the onset. Various autonomic function tests showed sympathetic and parasympathetic dysfunction of mainly postganglionic origins. Thus we diagnosed this patient as "pure" progressive autonomic failure ("pure" PAF). "Pure" PAF is a new entity described by Bannister and Oppenheimer in 1982. It shows symptoms of autonomic failure without other neurological disturbances which manifest as Shy-Drager syndrome. Treatment with L DOPS increased his blood pressure level and attenuated his symptoms due to orthostatic hypotension. PMID- 1460786 TI - [Effects of night shift on plasma concentrations of melatonin, LH, FSH and prolactin, and menstrual irregularity]. AB - To examine the effect of night shift on the ovarian function, 122 teachers, 67 office workers, 377 nurses, 133 factory workers and 67 barmaids were surveyed. The incidence of irregular menstrual cycle was 13.1% in teachers, 14.9% in office workers, 24.9% in nurses, 36.8% in factory workers and 40.3% in barmaids. The incidence was significantly higher in women working at night than women working during the day. Plasma concentrations of melatonin, LH, FSH and prolactin were determined at 2200 h and 0200 h in 5 nurses working at night and in 6 nurses resting in their quarters. Plasma concentrations of melatonin and prolactin at 0200 h were significantly lower in nurses of the working group than others of the resting group, but plasma concentrations of LH and FSH did not differ between the two groups. These results indicate that night shift suppresses the ovarian function by affecting the circadian rhythm of melatonin and prolactin. PMID- 1460787 TI - [A 4 degrees C-1 min method of cold water immersion test for peripheral circulatory function in fingers]. AB - To assess the validity of a new simplified cold water immersion test (4 degrees C 1 min method) for peripheral circulatory function, comparison was made with the conventional method (10 degrees C-10 min method). These two different methods of cold immersion test were applied to 23 patients with vibration disease and 24 healthy men. Observation was made on finger skin temperature by a thermistor and complaints in the hand by a 5-step self-reported scale method every minute during the test. The patterns of recovery of skin temperature after cold immersion in each group were similar in both methods. Pain in the hand in the 4 degrees C-1 min method was less than that in the 10 degrees C-10 min method. The recovery rate at 5 min in the patients with Raynaud's phenomenon was lower than that in those without Raynaud's phenomenon in the 4 degrees C-1 min method (p < 0.01). However, no significant differences were noted in 10 degrees C-10 min method. The results suggest that the new method is feasible in detecting the response of vasodilation after immersion. In the recovery rate at 5 min after immersion, near values of the sensitivity and specificity were observed between 50% cut-off values in the 4 degrees C-1 min method and 30% value in the 10 degrees C-10 min method. Thus, the 4 degrees C-1 min method is considered to be more useful to evaluate the physiological response after cold immersion than the 10 degrees C-10 min method. PMID- 1460788 TI - [Excretion of styrene in rats (Part I). Elimination of styrene in exhaled air]. PMID- 1460789 TI - [Validity of screening test for the evaluation of depressive state]. PMID- 1460790 TI - [Upper limit of hearing in workers exposed to organic solvents]. PMID- 1460791 TI - Can death at a low COHb concentration frequently observed in fire victims be explained by hypoxic hypoxia? AB - Fire deaths at low COHb (carboxyhemoglobin) concentrations are frequently observed, but it is difficult to determine the causative factors. Participation of hypoxic hypoxia was examined using rats and rabbits exposed to various low-O2 and CO gas mixtures. The ranges of O2 and CO concentration were 3.0-22.2% and 0.3 2.9%, respectively. The concentration of CO2 was fixed at about 5%. Rats were individually exposed to the test gas in a plastic chamber. Rabbits inhaled the test gas through a tracheal cannula. The survival time of rats ranged from 3.9 7.7 min, and that of rabbits was 8.0-22.5 min. Rats exposed to the most hypoxic gas mixture (O2 3%-CO 0.3%) died with COHb values below 40%. Rabbits also died with a low COHb concentration under this condition, but the COHb concentration was not below 50%. Rabbits were considered to be more resistant to hypoxic hypoxia than rats. From the literature on the relationship between the grade of burns and the concentration of COHb, as well as the findings obtained in the present experiment, hypoxic hypoxia did not appear to be a main factor causing death at low COHb concentrations. In the rabbit the COHb concentration increased exponentially and reached plateau levels within 10 min in many groups. The time required to reach a plateau COHb level was shorter when the concentration of CO was high and that of O2 was low. PMID- 1460792 TI - Postmortem changes of triazolam concentrations in body tissues. AB - Postmortem changes of triazolam concentrations in body tissues were examined using rats, in order to find the most suitable tissue samples for toxicological analysis. Triazolam was orally given to rats (5 mg/kg), and then the rats were sacrificed 1 hour after administration. Tissue samples were collected 0, 1 and 2 days after storage at 22-24 degrees C, and the triazolam concentration in each sample was measured using gas chromatography with a nitrogen phosphorus detector. Triazolam concentrations were markedly increased in the spleen, the abdominal muscle, the liver and the kidney, and were slightly increased in the blood and the lung. On the other hand, no changes were observed in the thigh muscle or the brain, and the value in the thigh muscle was similar to those in the blood samples collected immediately after death. The results indicate that triazolam diffuses into the surrounding tissues through the stomach wall after death, so that the thigh muscle and the brain have to be analyzed as well as the blood for a correct diagnosis of triazolam ingestion. PMID- 1460793 TI - VNTR polymorphism of the collagen type II, alpha 1 (COL2A1) gene detected by PCR. AB - The 3' side of the human type II collagen alpha 1 (COL2A1) gene contains a region consisting of a variable number of tandemly repeated short A + T-rich DNA sequences (VNTR). We amplified this region accurately by the polymerase chain reaction (PCR). Genomic DNA was purified from isolated buffy-coat cells, and thermostable Taq polymerase was used to amplify the target region. The amplification products were directly visualized after polyacrylamide gel electrophoresis. In this way, five alleles were distinguished in chromosomes from 33 unrelated Japanese, and named A, B, C, D, and E in decreasing order of length. The relative frequencies of the COL2A1 3' VNTR alleles A through E were 0.045, 0.075, 0.469, 0.015, and 0.393, respectively. Co-dominant segregation was observed in two informative families. The COLA2A1 3' VNTR locus was estimated to have a heterozygosity index of 62% and a polymorphic information content of 0.55. PMID- 1460794 TI - Serological and biochemical studies on En(a-) human erythrocytes in a Japanese family. AB - The propositus erythrocytes with phenotype En(a-), which was found in the first example of a Japanese family, reacted with anti-N serum weaker than the ordinary phenotype N erythrocytes. When the erythrocyte membranes of the propositus were subjected to SDS-PAGE, no glycophorin A was observed on the gel by PAS staining, whereas glycophorin B band was observed. The S and the s antigens of the propositus erythrocytes were appeared to be normal. These results suggested that N activity of the propositus erythrocytes may be derived from glycophorin B components on the erythrocyte membranes. The amounts of bound sialic acid of the erythrocyte membranes were significantly lower in the En(a-) erythrocytes than the ordinary OMN erythrocytes. Neither the OMN nor the En(a-) erythrocytes showed the agglutinability to Arachis hypogaea lectin. The number of lectin receptor sites on the En(a-) erythrocyte membranes was significantly lower than on the OMN erythrocyte membranes for Limulus polyphemus, Triticum vurgaris and Bauhinia purpurea lectins. These results provide further support for the contention that En(a-) cells lack the glycophorin A as major erythrocytes sialoglycoprotein on the membranes. PMID- 1460795 TI - A fatal case of a single stab wound penetrating the small, narrow atlantoaxial interspace. AB - A 73-year-old woman was found dead with a small wound on the nape of her neck. The wound was oval in shape, measuring about 0.6 cm in length along the major axis, with a slightly irregular margin. The wound injured the medulla oblongata through the atlantoaxial interspace, and reached the left vertebral artery. This wound was found to be the cause of death. The wound depth was 5 cm in length, with the direction of the wound canal from posterior-lower right to anterior upper left. The size and appearance of the wound corresponded to those of the horizontal section of a skewer used by the assailant. Such a fatal case due to a single stabbing of the medullar oblongata by the chance gliding of a skewer through the small, narrow atlantoaxial interspace is considered to be exceptional. PMID- 1460796 TI - [Presence of a PCR-inhibitor in hairs]. AB - A polymerase chain reaction (PCR) system was used to amplify the noncoding 333-bp region of mitochondrial DNA (mt333DNA) contained in DNA extracts from single human hairs, and the following results were obtained: 1) Using natural black hairs, mt333 DNA was always amplified from a 5-cm length of hair shaft sampled within a region 11 cm from the hair root, but it was not always amplified from a 5-cm region adjacent to this 11-cm region, and was not amplified in almost all cases when a 5-cm length of hair shaft was sampled from a region more than 16 cm distant from the hair root. DNA preparations not responding to PCR were colored dark brown. 2) Using natural white hairs, mt333DNA was amplified from almost all specimens even up to a length of 31 cm. 3) When natural black hairs were stained with an oxidation-type hair-staining agent (Bigen-5Ge), mt333DNA was never amplified even from the hair root portion, whereas the same staining treatment of white hairs did not influence the amplification of mt333DNA. In the cases showing no response on PCR, DNA preparations were also colored dark brown. 4) These dark brown DNA preparations inhibited completely the amplification of mt333DNA even after addition of purified DNAs. These results suggest that the dark brown substance in the DNA preparations inhibits the amplification of mt333DNA by the PCR method. We therefore investigated the mechanism responsible for the development of this inhibitor. It was found that hydrogen peroxide (a component of hair-staining agent) induced formation of water-soluble melanins from insoluble melanins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460797 TI - [Asphyxial death by laryngopharyngeal tumor--two autopsy cases]. AB - Case 1. A 44-year-old male died about 3 h after paracenteses of both palatine tonsils. A 6.5 x 2.5 x 2.0 cm tumor, caused by bleeding and edema, was revealed at medico-legal autopsy. This tumor extended from the right palatine tonsil to the right edge of epiglottis. The cause of death was determined to be acute asphyxia due to the obstruction of the airway by the tumor. Case 2. A 51-year-old female was thought to have been killed by manual strangulation. At medico-legal autopsy, three malignant tumors, each of which was not as large as the tip of the little finger, were found in the lower pharynx. There were no findings of acute asphyxia death. The cause of death was determined to be delayed asphyxia caused by the malignant tumors. PMID- 1460799 TI - [An autopsy case of fatal nicotine poisoning]. AB - A fatal case of nicotine poisoning is reported in which a 44-year-old female committed suicide in a short time by taking orally the eluate from tobacco. External examination showed no abnormal findings except for markedly dark red purple postmortem lividity, and internal examination demonstrated no pathological changes but the signs of sudden death. Through the toxicological investigation by GC and GC-MS, however, nicotine was detected in the solution which she had taken orally and in the blood, urine and the contents of the stomach and small intestine. The nicotine concentrations of the blood, urine and contents of stomach and small intestine were 6.3 micrograms/ml, 1.5 micrograms/ml, 30 micrograms/ml and 71 micrograms/g respectively, and enough to be lethal. PMID- 1460798 TI - [Fracture of the cervical spine caused by blow in patient with ankylosing spondylitis--a report of an autopsy case]. AB - Fracture of the cervical spine in a patient with ankylosing spondylitis is presented. A 43-year-old male was involved in a fight when drinking. He received blows to his face and the lower jaw, and fell backward on the street and died. The postmortem examination showed abrasions and subcutaneous hemorrhages on the face and the lower jaw. A transverse fracture was observed through the intervertebral disc space between the fifth and sixth cervical vertebrae. The cervical spinal cord was completely ruptured at the fracture site. Ossification of the supporting ligaments and anterior surface of dics were found. The spine was bony ankylosed. The alcohol levels of blood and urine were 2.95 and 3.84 mg/ml, respectively. The cause of death was paralysis of respiration. The victim had suffered from the ankylosing spondylitis for many years. His neck had no mobility. The X-ray films taken at age 42 showed complete ankylosis of the spine, so-called "bamboo" spine. It seemed that the blow to his face and the lower jaw caused hyperextension of the neck and easily caused the cervical fracture because of the loss of flexibility and fragility from osteoporosis in the ankylosed spine. PMID- 1460800 TI - MCI-826 is a potent and selective antagonist of peptide leukotrienes (p-LTs) and has characteristics distinctive from those of FPL 55712. AB - Antagonistic effects of a newly synthesized compound, (E)-2,2-diethyl-3'-[2-[2-(4 isopropyl)thiazolyl]ethenyl]succinanilic+ ++ acid sodium salt (MCI-826) on the contraction of the isolated guinea pig trachea and human bronchus induced by various agonists including peptide leukotrienes (p-LTs), histamine, acetylcholine (ACh), prostaglandin (PG) D2 and others were investigated and compared with the effects of a p-LT antagonist, FPL 55712, in some experiments. MCI-826 potently antagonized LTD4- and LTE4-induced contractions at extremely low concentrations in the isolated guinea pig trachea with pA2 values of 8.3 and 8.9, respectively, on a molar basis. These values indicated that MCI-826 is over 100 times stronger than FPL 55712. Similarly, MCI-826 at 10(-8) g/ml (2.4 x 10(-8) M) markedly antagonized LTD4-induced contractions of the isolated human bronchus. Although FPL 55712 fairly inhibited the 10(-9) g/ml LTC4-induced contraction of the isolated guinea pig trachea, MCI-826 had little effect on the contraction at high concentrations like 3 x 10(-6) g/ml (7.1 x 10(-6) M). MCI-826 modestly affected the other agonist-induced contractions and the resting tonus of the isolated guinea pig trachea at 10(-6) g/ml (2.4 x 10(-6) M) or higher concentrations, but FPL 55712 caused fair inhibition of some of those contractions and gradually lowered the resting tonus with time. These results indicate that MCI-826 is a highly potent and selective antagonist of LTD4 and LTE4 and can be a useful tool for biological and pharmacological experiments on p-LTs. PMID- 1460801 TI - Different modes of potentiation by beta-eudesmol, a main compound from Atractylodes lancea, depending on neuromuscular blocking actions of p-phenylene polymethylene bis-ammonium derivatives in isolated phrenic nerve-diaphragm muscles of normal and alloxan-diabetic mice. AB - The essential moieties in p-phenylene-polymethylene bis-ammonium (PMBA) derivatives, C6H4[X(CH2)nN+R3]2, on the potentiating effects by beta-eudesmol, a main component of Atractylodes lancea, of their neuromuscular blockades were investigated in isolated phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. PMBA derivatives were separated into the following three groups based on the patterns of the potentiating effects: group I: PMBA-23 (n = 6, R = Me) and PMBA-24 (n = 6, R = Et); group II: PMBA-1 (n = 4, R = Me), PMBA-21 (n = 4, R = Et) and PMBA-2 (X = O, n = 3, R = Me); and group III: PMBA-31 (X = S, n = 3, R = Me), PMBA-3 (X = CO, n = 3, R = Me) and PMBA-4 (X = CHOH, n = 3, R = Me). The pretreatment with 80 microM beta-eudesmol for 60 min did not affect group I-induced neuromuscular blocking action, and it potentiated group II and group III-induced ones. The potentiating effect of beta-eudesmol on group III was greater in diabetic muscles than in normal one and that on group II was to the same extent in both muscles. These results suggest that the four-methylene length of the side chains in normal muscles and the hydrophilic moieties adjacent to a phenylene ring in diabetic muscles are related to the potentiating effect by beta-eudesmol on PMBA derivatives. PMID- 1460802 TI - Assessment of the ambulation-increasing effect of ketamine by coadministration with central-acting drugs in mice. AB - The coadministration of ketamine (12.5 mg/kg, but not 3.1 mg/kg, s.c.) with methamphetamine (2 mg/kg, s.c.), cocaine (10 mg/kg, s.c.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) and MK-801 (0.1 mg/kg, i.p.) significantly enhanced the ambulation-increasing effects. Furthermore, in the coadministration with morphine (10 mg/kg, s.c.) and GBR-12909 (10 mg/kg, i.p.), not only 12.5 mg/kg but also 3.1 mg/kg of ketamine produced a significant enhancement. On the other hand, the ambulation-increasing effect of ketamine (12.5 mg/kg, s.c.) was significantly suppressed by ceruletide (0.01 mg/kg, i.p.), alpha-methyl-p-tyrosine (100 and 300 mg/kg, i.p. x 2), nimodipine (1 and 3 mg/kg, i.p.), haloperidol (0.03 and 0.1 mg/kg, s.c.), a low dose of apomorphine (0.1 mg/kg, s.c.), physostigmine (0.1 mg/kg, s.c.) and N6-(L-2-phenylisopropyl) adenosine (0.1 mg/kg, s.c.). However, imipramine (20 mg/kg, i.p.), 6R-L-erythro 5,6,7,8-tetrahydrobiopterin (100 mg/kg, s.c.), a high dose of apomorphine (0.5 mg/kg), reserpine (0.3 and 1 mg/kg, s.c.), propranolol (0.3 and 1 mg/kg, s.c.), phenoxybenzamine (3 and 10 mg/kg, s.c.) and naloxone (0.3 and 1 mg/kg, s.c.) scarcely interacted with ketamine. These results suggest that ketamine increases the ambulatory activity in mice by facilitating dopamine release from a newly synthesized pool at the presynaptic level, which is affected by a calcium dependent mechanism. PMID- 1460803 TI - Cetraxate improves ethanol-induced gastric mucosal congestion in anesthetized dogs. AB - Gastric mucosal microcirculatory disturbance in experimental animals is stressed as an important factor in the development of gastric ulceration induced by ethanol. In this study, we used a reflectance spectrophotometry system to investigate the effect of cetraxate on ethanol-induced gastric mucosal hemodynamics in anesthetized dogs. Forty percent ethanol caused a significant increase in the mucosal blood volume and a significant decrease in mucosal hemoglobin oxygenation. The changes in these parameters indicated mucosal congestion and tissue hypoxia. Topical administration of cetraxate (200 mg in 10 ml saline) prevented the increase in mucosal blood volume and decrease in mucosal hemoglobin oxygenation which had been induced by ethanol loading in the stomach. In conclusion, cetraxate showed a protective effect on mucosal microcirculation that resulted in the maintenance of the gastric mucosal integrity against ethanol loading in the gastric mucosa. PMID- 1460804 TI - Induction of gastric lesions by 2-deoxy-D-glucose in rats following chemical ablation of capsaicin-sensitive sensory neurons. AB - Effects of chemical ablation of capsaicin-sensitive sensory nerves on functional and mucosal ulcerogenic responses to 2-deoxy-D-glucose (2DG) were investigated in the rat stomach, in comparison with those of indomethacin, a prostaglandin (PG) biosynthesis inhibitor. Intravenous injection of 2DG (200 mg/kg) followed by infusion of this agent (100 mg/kg/hr, i.v.) significantly increased gastric acid secretion and motility, but rarely induced macroscopic damage in the gastric mucosa of normal conscious rats. Chemical ablation of capsaicin-sensitive sensory nerves or pretreatment with indomethacin (5 mg/kg, s.c.) did not significantly affect the acid secretory and motility responses to 2DG, but induced severe hemorrhagic lesions in the stomach within 4 hr. Gastric mucosal blood flow (GMBF) determined by laser Doppler flowmetry under anesthetized conditions did not consistently change during 2DG treatment in any of these three groups, but the rise in GMBF in response to mucosal acidification (0.2 N HCl) was significantly inhibited in the animals pretreated with indomethacin or following chemical deafferentation. We conclude that functional ablation of capsaicin-sensitive sensory neurons, similar to the PG deficiency, increases the gastric mucosal vulnerability during 2DG infusion (acid hypersecretion and hypermotility due to vagal excitation), resulting in hemorrhagic lesions, and that the mechanism may be accounted for at least partly by the impairment of gastric mucosal blood flow response to mucosal acidification. PMID- 1460805 TI - Cerebrovascular injuries induced by activation of platelets and leukocytes in vivo and their correction by neurotropin. AB - Ischemia-like brain damage was induced in cats by selective injection of 4 beta phorbol-12 beta-myristate-13 alpha-acetate (PMA) into the left carotid artery. PMA-injection provoked significant decreases in platelet and neutrophil counts due to their intravascular aggregation. Platelet and neutrophil aggregates caused brain edema with accumulation of sodium fluorescein in the cerebrospinal fluid and ipsilateral derangement of the cerebral energy state in the parietal cortex. Neurotropin administration decreased the changes in platelet and neutrophil counts and prevented the developments of both brain edema and cerebral energy failure. PMID- 1460806 TI - Beta-phenyl-beta-alanine prevents the activation of vagal efferent discharges evoked by baclofen and GABA in rats. AB - The effects of DL-beta-phenyl-beta-alanine (BPBA) on vagal efferent discharges elicited by gamma-aminobutyric acid (GABA) and baclofen were investigated in rats. When given alone, BPBA (40 mg/kg, i.v.) caused no significant change in vagal nerve response and did not elicit any convulsions. Pretreatment with BPBA (40 mg/kg, i.v.) resulted in 70% and 80% reductions in the vagal efferent discharges induced by GABA (400 mg/kg, i.v.) and baclofen (4 mg/kg, s.c.), respectively. The present results suggest that BPBA may be a novel GABA antagonist with respect to vagal activation mechanisms in the CNS. PMID- 1460808 TI - Protection by halothane of the vagal baroreflex system from transient global cerebral ischemia in dogs. AB - A possible cerebroprotective effect of halothane was investigated in a canine model of 5-min global cerebral ischemia. In pentobarbital-anesthetized dogs, additional inhalation of 0.5 to 1% halothane prior to ischemia prevented the post ischemic dysfunction of the vagal component of reflex bradycardia. In contrast, pretreatment with thiopental at 10 mg/kg, i.v. failed to prevent it. The influence of ischemia in the absence of anesthetics was similar to that under barbiturate anesthesia. The results suggest that halothane, but not barbiturate, may actively protect the vagal baroreflex system from ischemia. PMID- 1460807 TI - Inhibitory effects of magnoshinin and magnosalin, compounds from "Shin-i" (Flos magnoliae), on the competence and progression phases in proliferation of subcultured rat aortic endothelial cells. AB - Anti-proliferative effects of magnoshinin and magnosalin derived from "Shin-i" (Flos magnoliae) were investigated using subcultured endothelial cells (EC) of rat aorta. The inhibitory effects of magnoshinin were 2-fold greater at 10 micrograms/ml than that of magnosalin on the increase in cell number when EC were stimulated by 5% fetal bovine serum. In the 3H-thymidine incorporation monitored at 3 hr-intervals, magnoshinin (0.1-3 micrograms/ml) prolonged the starting time of DNA synthesis and reduced the rate of incorporation into EC. Magnosalin (0.3-3 micrograms/ml) reduced only the incorporation rate. These results suggest that magnoshinin inhibits both the competence phase and progression phase, but magnosalin preferentially inhibits the progression phase in EC proliferation. PMID- 1460809 TI - Anthralin, a non-TPA type tumor promoter, synergistically enhances phorbol ester caused prostaglandin E2 release from primary cultured mouse epidermal cells. AB - Primary cultures of mouse epidermal cells (i.e., target cells of skin tumor promotion) stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) release prostaglandin E2 within 30 min. Anthralin, a non-TPA type tumor promoter, also stimulated PGE2 release; however, no release was detectable at least up to 4 hr after the addition of anthralin. When the cells were incubated with TPA plus anthralin, both PGE2 and arachidonic acid release were synergistically enhanced. Other non-TPA type tumor promoters, i.e., chrysarobin, 7 bromomethylbenz[a]anthracene, benzoylperoxide, okadaic acid and palytoxin, did not potentiate the TPA-caused PGE2 release. In protein kinase C-down regulated cells, the synergistic stimulation of PGE2 and arachidonic acid release by TPA plus anthralin were not detected. Anthralin plus TPA did not alter the incorporation of arachidonic acid into cellular phospholipids. Cellular cyclooxygenase activity was increased 2 hr after TPA stimulation. Anthralin caused increase in cyclooxygenase activity was detected at 6 hr after the addition of anthralin. Cyclooxygenase activity was synergistically increased by treating the cells with TPA plus anthralin. Cycloheximide and actinomycin D inhibited the increase in cyclooxygenase activity caused by anthralin or TPA plus anthralin. These results indicate that anthralin synergistically stimulates TPA caused PGE2 release by synergistically increasing arachidonic acid release and cellular cyclooxygenase activity. PMID- 1460810 TI - All in the family. PMID- 1460811 TI - The doctrine of necessaries in Kansas. PMID- 1460812 TI - The cost of excess professional liability insurance. PMID- 1460813 TI - A core electronic medical library in a rural setting. Part II: The on-line system. PMID- 1460814 TI - MCAD deficiency in the Holderman Mennonite population in central Kansas. PMID- 1460815 TI - Safety belt use in Kansas, 1990-1991. PMID- 1460816 TI - Prothrombin times may be misleading. PMID- 1460817 TI - [Somatic disorders in psychopathies]. PMID- 1460818 TI - [Hemorrhagic vasculitis (diagnosis and treatment)]. PMID- 1460819 TI - [Fatty acids and malignant tumors]. PMID- 1460820 TI - [Acute suppurative-inflammatory diseases of the abdominal organs and diabetes mellitus]. PMID- 1460822 TI - [Diagnosis and therapeutic tactics in polycystic liver]. AB - The results of clinical observations of 60 patients with polycystosis of the liver who had been treated or examined by the authors in the period from 1964 to 1989 were summarized. The clinical course of the disease was featured by scanty clinical signs: pains in the upper half of the belly and hepatomegaly were most frequent. The combination of diagnostic techniques for verification of surgical intervention necessity was established. Besides, it was stated that the diagnosis of polycystosis of the liver should be complex and based on anamnestic data and the results of clinical, laboratory and instrumental investigations. Preference should be given to ultrasonography and computed tomography. Cysts with diameter of 5 cm and more, complicated polycystosis of the liver (bleeding, suppuration, malignancy) and cystic compression of the extrahepatic bile ducts and vessels (portal and cava inferior veins) were found to be indicative signs for surgical treatment of hepatic polycystosis. A total of 41 patients were subjected to surgical treatment with 49 operational procedures employed. Fenestration of hepatic cysts (42), that were organosparing operations, predominated. Resection of the liver was performed in 2 patients who had total cyst substitution for the whole of the left lobe. The improvement registered in 85.7% of operated on patients evidenced the favorable results of surgical treatment. PMID- 1460821 TI - [Changes in the indicators of total plethysmography and pulmonary hemodynamics in patients with bronchial asthma after the treatment with ditek]. PMID- 1460823 TI - [Indicators of the lithogenic properties of the bile: methods of their evaluation, clinical availability and informative value]. AB - Duodenal bile taken by gastroduodenal intubation of patients with chronic calculous cholecystitis with intact gallbladder performance was investigated as was the bile taken in those with chronic acalculous cholecystitis or in those without clinical signs of cholecystitis and concurrent diseases. The bile was investigated for cholesterol, bile acids and lecithin levels. All the parameters obtained were used for computation of lithogeny parameters: Swell, Admirand Small, Metzger, Thomas, Andrews and cholesterol-lecithin ratio. The study performed indicated that Swell's parameters of lithogeny and cholesterol-lecithin ratio displayed more precisely lithogeny of the bile, and could be determined more easily than other parameters. PMID- 1460824 TI - [Clinical value of determining serum levels of glycocholic acid in alcoholic lesions of the liver]. AB - To assess the diagnostic value of radioimmunoassay determination of serum levels of glycocholic acid in alcohol-induced chronic diffuse hepatic lesions, this technique was compared by sensitivity and informative content with conventional hepatic tests. Hepatocytic function was measured in combined examination of 83 patients and 30 controls. It is shown that serum glycocholic acid concentration permits detection of early alcohol defects of the liver, excretory dysfunction in particular, control of cholestatic changes, of transformation of hepatic steatosis into hepatitis or cirrhosis, evaluation of cholestasis. The above radioimmunoassay is a useful prognostic tool in decompensated alcohol cirrhosis of the liver. PMID- 1460825 TI - [Ultrasonographic diagnosis of tumors of the gallbladder]. AB - The role of echography in the diagnosis of gallbladder tumors was investigated. Benign tumors (papilloma and adenoma) were diagnosed in 2 patients and carcinoma in 18 subjects. This technique failed to diagnose carcinoma in 2 patients. Two more procedures had false-positive results (in one patient multiple clots in the dramatically enlarged bladder were taken for the tumor while ++post-inflammatory granulation in the other patient was mistaken for the tumor as well). Echographical signs of gallbladder tumors were presented, as were the criteria permitting one to differentiate carcinoma from other pathological formations in the gallbladder (echogenic bile, cholesterol polyps, cholecystitis, adenomyomatosis). High informative value of echographic investigation in the diagnosis of gallbladder tumors was noted. PMID- 1460826 TI - [Miliary tuberculosis developed after cured lymphogranulomatosis]. PMID- 1460827 TI - [Therapeutic tactics in the early period of long-term crush syndrome]. PMID- 1460828 TI - [Use of methotrexate in the treatment of rheumatoid arthritis]. PMID- 1460829 TI - [Problem of osteopoikilosis]. PMID- 1460830 TI - [2 cases of congenital mucopolysaccharidosis]. PMID- 1460831 TI - [Development of pre-excitation syndrome after long-term administration of cardil]. PMID- 1460832 TI - [Clinical variants of the course of atrial myxoma]. PMID- 1460833 TI - [Conservative treatment of cholelithiasis with chenodeoxycholic and ursodeoxycholic acid preparations]. PMID- 1460834 TI - [Diagnosis of acute diarrheal infections]. PMID- 1460835 TI - [Iron deficiency anemia and conditions (diagnosis, treatment and prevention]. PMID- 1460836 TI - A restraining device for ophthalmic examination of unanesthetized rats. PMID- 1460837 TI - An approved method of endotracheal intubation in rabbits. PMID- 1460838 TI - Xylazine is known to cause arrhythmias in several species. PMID- 1460839 TI - Muhlbock Memorial Lecture: man, microbes, and models. PMID- 1460840 TI - Subclinical infection and transmission of Tyzzer's disease in rats. AB - Two isolates of Bacillus piliformis originally obtained from rats from Japan and Indiana were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Protein and antigen profiles revealed heterogeneity between the two isolates, demonstrating that more than one isolate of B. piliformis is capable of infecting rats. Results of parallel infection and transmission studies with the two isolates were almost identical. Orally inoculated rats remained asymptomatic; however, enzyme-linked immunosorbent assay results revealed a significant increase in serum antibodies to B. piliformis. Formalin-killed B. piliformis elicited no serum antibody response among rats inoculated orally, indicating that viable organisms, capable of replicating within the host, are needed to induce a systemic humoral response. Naive rats and weanling gerbils were housed on soiled bedding from the experimentally infected, asymptomatic, seropositive rats. Although gerbils showed no clinical signs or histopathologic evidence of Tyzzer's disease, rats housed on bedding collected 1 or 2 weeks postinoculation seroconverted and remained seropositive but asymptomatic throughout the study. These results demonstrate that subclinically infected rats are capable of transmitting B. piliformis to naive rats and suggest that the histopathologic evaluation of sentinel gerbils may not be an effective method for detecting all strains of B. piliformis. PMID- 1460841 TI - Rederivation of rat colonies seropositive for Bacillus piliformis and the subsequent screening for antibodies. AB - Latent infection of rats in a breeding colony with Bacillus piliformis detectable by antibodies to the agent in an immunofluorescence assay was eliminated by a combination of traditional rederivation techniques, using animal units not previously used for rat breeding, and the use of specific disinfection procedures. The success rate was apparently correlated with the use of peracetic acid instead of aldehyde products to decontaminate the animal unit. PMID- 1460842 TI - Correlation between megaloileitis and antibodies to Bacillus piliformis in laboratory rat colonies. AB - Rat colonies in which antibodies to Bacillus piliformis were detected in animals examined at the age of 8 to 15 weeks were compared with rat colonies where no such antibodies were present. The seropositive colonies had a low incidence of megaloileitis in 5-week-old rats of Sprague-Dawley stock and some few inbred strains. In seronegative colonies, no megaloileitis was detected. In rats with megaloileitis, significantly high titers to B. piliformis were noted and the agents could be identified in the ileal mucosa by immunofluorescence technique. PMID- 1460843 TI - Pulmonary clearance of Mycoplasma pulmonis in rats with respiratory viral infections or of susceptible genotype. AB - We sought to determine whether or not increased severity of bronchopulmonary disease due to Mycoplasma pulmonis infection in rats with respiratory viral infections and in rats of susceptible genotype could result from altered pulmonary clearance. Pathogen-free rats were exposed to aerosols of radiolabeled M. pulmonis and the numbers of M. pulmonis colony-forming units, and amounts of radiolabel in the lungs were determined immediately after exposure or 4 hours later. Intrapulmonary killing of M. pulmonis during the 4-hour interval was determined from decreases in ratios of colony-forming units to radiolabel, and physical clearance was determined from decreases in radiolabel. Neither intrapulmonary killing nor physical clearance differed between control F344 rats and F344 rats inoculated with Sendai virus or sialodacryoadenitis virus, or between F344 and LEW rats. Rates of intrapulmonary killing and physical clearance were 64 +/- 3% and 44 +/- 2%, respectively (overall means +/- standard error). PMID- 1460844 TI - Naturally occurring aortic aneurysms in owl monkeys (Aotus spp.). AB - Spontaneous aortic aneurysms were diagnosed in 22 owl monkeys (Aotus spp.) at necropsy. There were 6 males and 16 females. Clinical findings varied including weight loss, weakness, and lethargy and were not present in all animals. Aortic lesions ranged in size from 2 mm to 3 cm in diameter. Nineteen of the aneurysms were classified histologically as dissecting and three as saccular. Lesions occurred less often in karyotype I monkeys than in karyotype II or III monkeys. The etiopathogenesis of aortic aneurysm in owl monkeys is unknown. PMID- 1460845 TI - Transplantation of half kidneys in swine: I. Long-term survivors of hemirenal autotransplants. AB - We describe a novel model of hemirenal transplantation in swine wherein one-half of one kidney is autotransplanted by modifications of standard vascular anastomoses and ureteropyelostomy. Two pigs with hemirenal transplants performed in this manner have not only survived but have grown normally and had decreased but stable renal function for more than 1 year. The model confirms that one fourth of the total renal mass is sufficient to sustain life and growth in pigs. It is anticipated that this model could be used to study the effects of renal ablation on remnant nephrons in pigs. PMID- 1460846 TI - Regulation of phosphoenolpyruvate carboxykinase mRNA in mouse liver, kidney, and fat tissues by fasting, diabetes, and insulin. AB - Previous investigations of the phosphoenolpyruvate carboxykinase (PEPCK) gene have been conducted using rats. In a recent comparative study, we investigated, for the first time, the effects of fasting, refeeding, alloxan-induced diabetes, and insulin treatment on the levels of PEPCK mRNA in mouse liver, kidney, and adipose tissues. As in rats, fasting and diabetes induced, while insulin repressed, hepatic PEPCK mRNA. In contrast, the response of renal PEPCK mRNA to fasting, refeeding, and diabetes in mice differed quantitatively with that in rats: fasting caused a twofold increase in mice and a fourfold increase in rats. Moreover, diabetes, which induces renal PEPCK mRNA indirectly by causing acidosis in rats, was without effect in mice. In adipose tissue, the results of previous studies in both rats and mice have shown that the amount of PEPCK protein and its rate of synthesis are increased by fasting and diabetes and decreased by refeeding and insulin treatment. Thus, it was surprising to find that fasting, refeeding, alloxan-induced diabetes, and insulin treatment had no effect on adipose tissue PEPCK mRNA in either rats or mice. PMID- 1460847 TI - Evaluation of maternal and fetal factors in reduced postnatal survival of NC-eob mutant mice. AB - It has been reported that mouse pups bearing a newly identified mutation, eyelids open at birth (eob), as a homozygous condition often die within 7 days after birth although they have no external malformations other than open eyelids. We sought to determine what factors influence the viability of eob pups by performing a cross-fostering experiment using NC and NC-eob mice which are co isogenic with each other. Viability indices of NC pups during days 0 to 7 of lactation were approximately 95% or more when they were fostered by either NC or eob mothers. However, the viability indices of eob pups were reduced to 87.3% and 36.7% when they were fostered by NC and eob mothers, respectively. Body weight gains of both NC and eob pups were slightly inhibited during the entire lactation period when they were fostered by eob mothers. In a second experiment, eob mothers were examined for milk-yielding capability and the fetuses examined for the presence of congenital visceral and skeletal malformations. Neither decreased amounts of suckled milk nor malformations were observed. Based on these results, we concluded that a remarkably high mortality of eob pups would be caused only when weak lethal factors in eob pups were combined with the slightly depressed pup-rearing capability in eob mothers. PMID- 1460848 TI - Evaluation of greyhound susceptibility to malignant hyperthermia using halothane succinylcholine anesthesia and caffeine-halothane muscle contractures. AB - We investigated Greyhounds because of prior reports of malignant hyperthermia (MH) episodes and because Greyhounds may express high genetic relatedness due to inbreeding for generations. Seven Greyhound and six mongrel dogs were given halothane and succinylcholine anesthesia as a challenge to trigger MH. They also underwent semitendinosus muscle biopsy for contracture study with halothane and caffeine. Measurements in vivo of mixed venous and arterial blood gases, cardiac output by thermodilution, temperature, blood pressure, and pulse rate provided sequential data regarding whole body O2 consumption (product of cardiac output and arterial-mixed venous O2 content difference), acid-base status, and arterial CO2 tension. Greyhounds and mongrels had uniformly similar in vivo and in vitro responses, without evidence for MH. Contracture thresholds were higher than those reported for normal swine and humans (8 mM vs. 4 mM). Information on MH susceptibility in this breed is important for laboratory investigation in Greyhounds as well as to veterinary medicine in general. Neither mongrels nor this group of Greyhounds were obviously susceptible to MH. If all Greyhounds are genetically homologous, then Greyhounds may not be specifically MH susceptible. These findings overall may provide a protocol and baseline normal comparative data for determining MH susceptibility in dogs and other species. PMID- 1460849 TI - Effects of epinephrine, phenoxybenzamine, and propranolol on maximal exercise in sheep. AB - The mixed adrenergic agonist, epinephrine (10 micrograms/kg, i.v.), the beta adrenergic receptor antagonist, propranolol (0.2 mg/kg, i.v.), or the alpha adrenergic receptor antagonist, phenoxybenzamine (1 mg/kg, i.v.), were administered to sheep immediately before maximal incremental exercise. The effects of each of these drugs on hemoglobin (Hb) concentration during maximal exercise and on maximal exercise performance were investigated. The maximal incremental exercise protocol began at 4.0 km/h and 0% grade and finished at 5.6 km/h and 12% grade, with speed or grade increases every 1.5 minutes. Maximal exercise in control (untreated) sheep caused a mean 42% increase in hematocrit and 44% increase in Hb. This exercise-induced increase in Hb was unaffected by propranolol but was partially blocked by phenoxybenzamine. Epinephrine caused an immediate increase in Hb which abated during the early minutes of exercise and then subsequently increased toward the end of the exercise challenge. Maximum oxygen consumption (VO2) in control sheep was 47.6 +/- 6.7 ml/min per kilogram. Maximum VO2 after epinephrine, 51.6 +/- 8.7 ml/min per kilogram, was not significantly different from control. Maximum VO2 after propranolol and phenoxybenzamine, 35.4 +/- 15.3 and 40.8 +/- 8.2 ml/min per kilogram, respectively, were both significantly less than control exercise (P < 0.05). PMID- 1460850 TI - Bronchoalveolar eosinophilia in random-source versus purpose-bred dogs. AB - Eosinophils (EOS) have been implicated in changes in airway and vascular reactivity in a variety of disease states. Analysis of cells in bronchoalveolar lavage samples from chronic, heartworm-free random-source (RS) dogs indicated higher leukocyte counts with markedly higher percent and total numbers of EOS than were present in purpose-bred (PB) animals. Bronchoalveolar lavage fluid (BALF) obtained from RS dogs had a significantly elevated total nucleated cell count: 0.8 x 10(6) vs 0.4 x 10(6) for the PB dogs. RS dogs had 24% +/- 5% and PB dogs had 3% +/- 0.7% EOS. The RS animals with elevated EOS had similar percentages of neutrophils: 4% +/- 0.6% as the PB animals. Despite aggressive anthelminthic treatment, the abnormal BALF cellular profile of the RS animals persisted even though circulating levels of EOS in this group decreased. Analysis of BALF for thromboxane B2 (TxB2) and 6-keto-prostaglandin F1(1a) (6-keto-PGF1a) indicated that only the TxB2 levels were significantly different between groups. The RS BALF TxB2 levels were 73 +/- 14 pg/ml vs 23 +/- 3 pg/ml for the PB group (P < 0.05). Regression analysis of the relationship between increasing TxB2 levels and the absolute number of EOS per milliliter of BALF obtained from the RS dogs indicated a significant correlation (r = 0.83, P < 0.0001). No difference in plasma levels of these mediators was observed. Other physiologic parameters also differed between the two groups: the RS group had significantly increased heart rates and cardiac output under baseline conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1460851 TI - Evaluation of Telazol-xylazine as an anesthetic combination for use in Syrian hamsters. AB - The availability of safe parenteral anesthetics for use in Syrian hamsters is limited. We evaluated the effects of Telazol-xylazine (TZX) combinations with respect to anesthetic efficacy and potential for tissue damage. Two dose levels of the combination were administered by both the intraperitoneal (IP) and intramuscular (IM) routes. TZX by the IM route failed to consistently produce anesthesia and caused gross and histopathologic muscle lesions. IP administration of 20 mg/kg Telazol combined with 10 mg/kg xylazine was adequate for restraint purposes. IP administration of 30 mg/kg Telazol combined with 10 mg/kg xylazine produced a safe, reliable level of surgical anesthesia without evidence of gross or histopathologic lesions. There was no nephrotoxicity at either concentration of the anesthetic. A dose level of TZX that provides safe parenteral anesthesia in Syrian hamsters was determined. PMID- 1460852 TI - A comparison of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits. AB - We evaluated and compared the effects of medetomidine-propofol and medetomidine midazolam-propofol anesthesia in rabbits. Fourteen New Zealand White rabbits were randomly assigned to receive either medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-propofol (4 mg/kg, i.v.) (n = 7) or medetomidine (0.25 mg/kg, i.m.) atropine (0.5 mg/kg, i.m.)-midazolam (0.5 mg/kg, i.m.)-propofol (2 mg/kg, i.v.) (n = 7). Five minutes after medetomidine-atropine or medetomidine-atropine midazolam i.m. injection, propofol was administered i.v. Both medetomidine and medetomidine-midazolam rapidly (within 5 minutes) immobilized all rabbits and greatly eased the i.v. administration of propofol. Endotracheal intubation was accomplished easily after propofol injection in both groups. There was no significant difference between medetomidine-propofol and medetomidine-midazolam propofol-treated rabbits in heart rate, respiratory rate, mean arterial pressure, or end-tidal CO2. The addition of midazolam to the medetomidine-propofol regimen significantly (P < 0.05) prolonged the duration of ear-pinch analgesia (25.0 +/- 7.1 vs. 36.7 +/- 8.9 minutes), the time from extubation to sternal recumbency (0.0 vs. 26.7 +/- 8.1 minutes), and the time from extubation to standing (0.0 vs. 39.5 +/- 11.3 minutes) without inducing significant changes in arterial blood pressure and end-tidal alveolar CO2. We consider both medetomidine-propofol and medetomidine-midazolam-propofol combinations to be safe and effective regimens for induction and short-term anesthesia in rabbits. PMID- 1460853 TI - Improved techniques for successful neonatal rat surgery. AB - Problems encountered in neonatal rat surgery include mortality due to anesthesia and postoperative mortality due to cannibalism or neglect by the dam. We required a method of anesthesia which would enable us to perform complicated, lengthy, recovery eye surgery on day-old rat pups. Because ethical concerns have been raised regarding hypothermia, the currently recommended procedure for anesthesia of newborn rats, we adapted two effective techniques for anesthetizing adult rats for use in neonates. In the first of these methods, halothane was administered via a gas anesthetic machine which allowed for precise regulation of anesthetic levels. The second method employed diluted Innovar-Vet, a neuroleptanalgesic drug combination that is easily administered by injection, with oxygen supplementation. Because each surgical procedure required 30 to 45 minutes and was technically demanding, it was important to minimize the loss of experimental animals due to cannibalism. To accomplish this, we developed an easy, noninvasive method to encourage acceptance of surgically manipulated pups by the dam, which included hand gentling and olfactory conditioning of pregnant females. All pups (63/63) survived eye surgery under halothane anesthesia and of those examined 7 days later, 55/57 (97%) were alive and appeared normal. Of the pups treated with Innovar-Vet, 16/16 (100%) survived anesthesia and all were normal in appearance when examined 7 days later. Our results suggest that using these anesthetic methods coupled with appropriate conditioning of the dam and handling of the pups contribute to successful neonatal rat surgery. PMID- 1460854 TI - Diagnostic exercise: anemia in a baboon. PMID- 1460855 TI - Encephalitis in gerbils due to naturally occurring infection with Bacillus piliformis (Tyzzer's disease). PMID- 1460856 TI - Isolation of Streptobacillus moniliformis from a guinea pig with granulomatous pneumonia. PMID- 1460857 TI - Roberts-SC phocomelia syndrome in a baboon (Papio anubis). PMID- 1460858 TI - A new technique for the cannulation of the rat thoracic duct. PMID- 1460859 TI - Is endothelin-1 the regulator of myofibroblast contraction during wound healing? PMID- 1460860 TI - Mechanisms of cancer-induced hypercalcemia. AB - Cancer-associated hypercalcemia is due to the: (a) elaboration of systemically acting humoral factors by neoplasms which alter calcium metabolism in bone, kidney, and intestine; or (b) stimulation of bone resorption at sites of tumor metastasis to bone. It is likely that both mechanisms occur in the same patient with certain neoplasms. There are many humoral factors that can be produced by tumors, secreted into the circulation, and have distant effects which induce hypercalcemia. The stimulation of increased osteoclastic bone resorption is a principal feature of humoral hypercalcemia of malignancy, but the kidney also plays an important role. In addition, intestinal absorption of calcium may be a factor in the pathogenesis of hypercalcemia in certain neoplasms. Parathyroid hormone-related protein plays a dominant role in the pathogenesis of HHM. PTHrP alone is able to induce nearly all of the clinical signs of HHM in experimental animals, but other humoral factors, such as cytokines, can interact with PTHrP to contribute to the development of hypercalcemia. Neoplasms which metastasize widely to bone and induce local osteoclastic bone resorption, such as multiple myeloma, also are capable of inducing hypercalcemia. Based upon existing data it is not clear what percentage of neoplasms which metastasize to bone and stimulate local bone resorption also are capable of stimulating hypercalcemia by systemic factors. Future research is needed to delineate the systemic and local factors associated with CAH; to define interactions of humoral factors in the pathogenesis of hypercalcemia; and to investigate the regulation of transcription, translation, modification, and secretion of hypercalcemia-inducing factors in normal and neoplastic tissues. PMID- 1460861 TI - Effect of endothelin-1 on croton oil-induced granulation tissue in the rat. A pharmacologic and immunohistochemical study. AB - BACKGROUND: To date no attempts have been made to determine the role of the endothelial cell derived product, endothelin-1 (ET-1) in granulation tissue development. This study investigates the cellular immunolocalization of ET-1 and its pharmacologic effect on myofibroblast-mediated rat croton oil-induced granulation tissue contraction. EXPERIMENTAL DESIGN: The distribution, cellular localization and temporal production of ET-1 in the tissues was determined by immunohistochemistry at days 7, 14, 21, and 28. The contractile response of the granulation tissue to ET-1 was tested over the same time period, and it effects modified by use of calcium antagonists. The pharmacologic profile was correlated to the ultrastructural development of contractile fibroblast-like cells within the tissue. RESULTS: Endothelin-1 caused reversible concentration-dependent contraction of the granulation tissue. The 21-day granulation tissue was the most responsive, with a maximum increase in tension of 458.9 +/- 41.1 mg; this response could be inhibited by use of calcium antagonists. Of the calcium antagonists tested, verapamil (1 x 10(-4) M) was the most potent inhibitor, giving a 43% reduction in maximum amplitude of the response. It is suggested that entry of extracellular calcium via the L-type potential operated calcium channel, is involved in ET-1 induced responses in contractile fibroblast-like cells or myofibroblasts. Ultrastructural analysis showed a correlation between the pharmacologic sensitivity of the tissue and the development of contractile fibroblast-like cells. The number of cells expressing the phenotypic characteristics of a myofibroblast increased with time, and were first observed at day 7. Immunohistochemistry revealed the presence of increasing numbers of ET 1 labeled cells throughout the time course of study. The ET-1 positive cells were localized to the capillaries. Immunolabeling of serial sections with the rodent endothelial cell specific lectin, Bandeiraea simplicifolia isolectin B4 and factor VIII-related antigen, confirmed the specific localization of ET-1 to endothelial cells. CONCLUSIONS: We present evidence that ET-1 may be an endogenous modulator of myofibroblast-mediated granulation tissue contraction and that the use of calcium antagonists could afford a possible therapeutic control in the treatment of fibrocontractive diseases. PMID- 1460862 TI - Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts. AB - BACKGROUND: Heparin increases alpha-smooth muscle actin expression in smooth muscle cells in vivo and in vitro. It has been recently suggested that alpha smooth muscle actin expression in fibroblasts is a marker of myofibroblastic differentiation. We have examined the effect of heparin and of four nonanticoagulant heparin derivatives on alpha-smooth muscle actin expression by fibroblasts in vitro and in vivo. EXPERIMENTAL DESIGN: For in vitro experiments, heparin was added for 7 days to different fibroblastic cultures. We studied cell proliferation and alpha-smooth muscle actin protein and mRNA expression. For in vivo studies, osmotic minipumps filled with NaCl or tumor necrosis factor-alpha without or with nonanticoagulant heparin were implanted subcutaneously. After 14 days, newly accumulated connective tissues around the pumps were processed for immunofluorescence and electron microscopic and biochemical studies. RESULTS: In vitro, heparin inhibited proliferation and increased the expression of alpha smooth muscle actin protein and mRNA. Analysis of [3H]thymidine incorporation in synchronized cells suggested that heparin produces a selection of alpha-smooth muscle actin expressing cells. In vivo, the local application of tumor necrosis factor-alpha resulted in formation of a typical granulation tissue: immunofluorescence showed that accumulated fibroblastic cells express alpha smooth muscle actin only in the presence of heparin derivatives. In tumor necrosis factor-alpha treated animals, electron microscopic examination established the presence of myofibroblasts, but alpha-smooth muscle actin was expressed in microfilament bundles only in the presence of heparin derivatives. CONCLUSIONS: These results show that heparin and its nonanticoagulant derivatives influence the expression of alpha-smooth muscle actin in fibroblastic cells both in vitro and in vivo and that this effect is probably related to the selection of a particular cell subpopulation. They suggest a possible role for heparin during the formation and evolution of granulation tissue. PMID- 1460863 TI - Intracellular actin as a marker for myofibroblasts in vitro. AB - BACKGROUND: Myofibroblasts are found in a wide variety of normal tissues and pathological conditions. It is suggested that myofibroblasts are derived from normal fibroblasts and share with smooth muscle cells the expression of actin microfilament bundles. The aim of this study was to establish if the myofibroblast phenotype from tissue expander capsules and Dupuytren's nodules could be distinguished from normal dermal fibroblasts by quantitation of intracellular actin and the ratio of polymerized (filamentous) actin to nonpolymerized (globular) actin. EXPERIMENTAL DESIGN: Cell lines were established from six patients from each group. In addition to quantitation of intracellular actin, the cells were characterized by criteria of light microscopy, ultrastructure, actin immunofluorescence, and growth rates. RESULTS: Dermal fibroblasts were the smallest and the most spindle-shaped but grew rapidly and had few actin microfilament bundles. By contrast, myofibroblasts from expander capsules were larger and more stellate, proliferated slowly, and had the most prominent microfilament arrays. Cells from Dupuytren's nodules were intermediate in phenotype. Substantial and significant differences in intracellular actin contents were found, ranging from 0.69 +/- 0.05 micrograms/10(4) cells in fibroblasts and 0.77 +/- 0.15 micrograms/10(4) cells for Dupuytren's nodule cells to 1.46 +/- 0.44 micrograms/10(4) cells in expander capsule myofibroblasts (p < 0.05). Similar findings were found with respect to ratios of fibroblast to globular actins, being 0.22 for fibroblasts and 0.38 for Dupuytren's nodule cells compared with 0.70 for expander capsule myofibroblasts (p < 0.01). CONCLUSIONS: Measurement of intracellular actin contents and fibroblast:globular actin ratios offers a rapid, sensitive, and reliable technique for establishment of the myofibroblast phenotype and has considerable advantages over traditional ultrastructural approaches for the study of myofibroblast differentiation/regression and in vitro responses to experimental manipulation. PMID- 1460864 TI - A morphometric study of the blood-brain barrier in Alzheimer's disease. AB - BACKGROUND: Abnormalities in the human blood-brain barrier may contribute to the pathogenesis of Alzheimer disease (AD). EXPERIMENTAL DESIGN: Morphometric parameters relevant to integrity of the blood-brain barrier (cerebral capillary endothelium) were assessed in brain biopsies from patients with AD and compared with values from age-matched nondemented controls. RESULTS: Alzheimer patients showed diminished mitochondrial density and area within cerebral capillary endothelium, an increased number of capillary profiles containing pericytes (a possible second line of defense when the capillary endothelium fails), and features of inter-endothelial junctions that suggest 'leakiness' of the blood brain barrier. CONCLUSIONS: The data indicate subtle but definite abnormalities suggesting compromise of the blood-brain barrier in AD that may contribute to its pathogenesis, and support neuropharmacologic and morphologic studies that suggest that a form of denervation microangiopathy may occur in AD brain, possibly secondary to loss of neurons from the pontine locus ceruleus. The changes may also play a role in the deposition of A4 Alzheimer amyloid within cerebral microvessel walls. PMID- 1460865 TI - Involvement of activated periglomerular leukocytes in the rupture of Bowman's capsule and glomerular crescent progression in experimental glomerulonephritis. AB - BACKGROUND: In an experimental model of crescentic glomerulonephritis, we have investigated whether periglomerular leukocytes are involved in (a), the disruption of Bowman's capsule (BC), and (b) the progression of cellular crescents. EXPERIMENTAL DESIGN: Experimental crescentic glomerulonephritis was induced in inbred Sprague-Dawley rats using passive accelerated anti-glomerular basement membrane disease. Groups of 4 animals were sacrificed at 3, 7, 14, 21, and 28 days after administration of nephrotoxic serum. RESULTS: Periglomerular infiltration of macrophages and T cells was evident at day 3, although focal accumulation of activated mononuclear cells (IL-2R+) was not apparent in this area until day 14. BC rupture in some glomeruli was first evident at day 14, and this was seen in all 12 animals from days 14 to 28. Similarly, glomerular crescent formation was first apparent at day 14, and from days 14 to 28, 11 of 12 animals displayed crescent formation (25 to 74% crescentic glomeruli). Examination of glomeruli (> or = 200/animal) within periodic acid-Shiff stained sections found that BC disruption invariably occurred at sites of prominent focal periglomerular mononuclear cell infiltration. Monoclonal antibody labeling revealed that T cells and IL-2R+ cells were restricted to focal infiltrates at sites of BC rupture, whereas macrophages were more widely distributed throughout the periglomerular area. A key finding was that while BC disruption occurred in both the presence and the absence of crescent formation, it was always associated with prominent periglomerular leukocytic infiltration. In this model, most cellular crescents contained leukocytes (88.8 +/- 2.1%). In the presence of an intact BC, macrophages constituted the predominant leukocyte cell type within these crescents. However, when BC was ruptured, although the number of macrophages remained unchanged, a marked accumulation of both T cells and IL-2R+ cells occurred within crescents. Progressive fibrous organization of cellular crescents was observed only in those glomeruli in which BC was disrupted. CONCLUSIONS: The results suggest that: (a) activated periglomerular mononuclear cells may cause disruption of BC via a delayed-type hypersensitivity mechanism, (b) rupture of BC facilitates entry of activated periglomerular T cells and fibroblasts into Bowman's space leading to progressive fibrous organization of cellular crescents, and (c) disruption of BC may be a general mechanism of progressive glomerular damage mediated by periglomerular leukocytes irrespective of crescent formation. PMID- 1460866 TI - Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis. AB - BACKGROUND: Cross-reactivity between anti-DNA antibodies and heparan sulfate (HS)/heparan sulfate-proteoglycan (HS-PG) of glomerular basement membrane has been previously reported. Conceivably, this determines the final outcome of glomerular injury in lupus nephritis. EXPERIMENTAL DESIGN: We investigated the status of glomerular injury in NZB/NZW F1 mice after the administration of rabbit anti-HS-PG antibody (experiment group). The controls received normal rabbit IgG only. RESULTS: All experimental animals became proteinuric 2 weeks after the administration of anti-HS-PG. The animals of the older age group (16 weeks) had significant hematuria as well. Their glomeruli exhibited hypercellularity with a heavy influx of polymorphonuclear leukocytes and monocytes into their capillaries, and some of them exhibited crescentic changes. Electron-dense deposits were present in subepithelial, subendothelial, and mesangial regions of the glomeruli. The control group had normocellular glomeruli with a few mesangial deposits. Mouse IgG and C3 displayed a granular pattern of immunofluorescence in the experimental group. Anti-rabbit IgG titers in the serum were higher in the control group, which lower in the renal glomerular eluates. No significant differences were observed in the concentrations of anti-dsDNA and -ssDNA either in the sera or in the eluates. There was also no difference between the control and experimental group in terms of antibody synthesis by the splenic lymphocytes and their proliferation subsequent to antigenic challenge. CONCLUSIONS: Data suggest that administration of anti-HS-PG accentuates the glomerular injury during the natural course of lupus nephritis in (NZB/NZW F1 mice; seemingly these two antibodies (anti-HS-PG and -DNA) do not competitively inhibit the binding of the other to the same anionic sites of glomerular basement membrane enriched with heparan sulfate in vivo. PMID- 1460867 TI - Tubule-tubule and tubule-arteriole contacts in rat kidney distal nephrons. A morphologic study based on computer-assisted three-dimensional reconstructions. AB - BACKGROUND: Functional investigations of the tubulo-glomerular feedback mechanism have indicated the existence of a contact between the distal nephron and the macula densa region. The structural justification of such a contact is investigated. EXPERIMENTAL DESIGN: Tubule-tubule and tubule-arteriole contacts were investigated in distal nephrons from normal rat kidneys. Computer-assisted three-dimensional reconstructions of distal nephrons were made from serial sections of renal cortical tissue and selected sections were examined by electron microscopy. RESULTS: In 14 of 15 reconstructed nephrons, the distal convoluted tubule or the connecting tubule approached the macula densa region. A wall-to wall contact between two tubules corresponding to a three-dimensional distance below 28 microns between the axes of the two tubules was found in only five of the reconstructed tubules. The distal nephron contacts to afferent and efferent arterioles of the same nephron were also examined. The efferent arteriole revealed no consistent contacts but the afferent arteriole contacted the distal convoluted tubule/connecting tubules consistently in all 10 of the superficial nephrons and in 3 of 5 midcortical nephrons. Electron microscopy confirmed a close contact between the distal tubule and the afferent arteriole in superficial nephrons and small nerves were often found at or near the site of contact, but the morphology at the site of contact was not unique. The arteriole contacts were made with late distal convoluted tubules, connecting tubules, or cortical collecting ducts. CONCLUSIONS: In conclusion, the present study shows that tubule tubule contacts are inconsistent between the macula densa region and the distal nephron but that the tubule-afferent arteriole contact is consistent and close in superficial nephrons. This morphology is compatible with the existence of a feedback mechanism between the superficial distal nephron and the afferent arteriole, apart from the one located at the juxtaglomerular apparatus. PMID- 1460868 TI - Identification of beta-subunit of GTP-binding regulatory protein in mitotic spindle. AB - BACKGROUND: The heterotrimeric GTP-binding regulatory protein (G protein) is important in membrane signal transduction. Since the function of the beta-subunit of G protein (G beta) in tumor cells is not well-documented, identification of G beta in tumor cells was performed. EXPERIMENTAL DESIGN: Immunolocalization, Western blotting, and immunoprecipitation of G beta in mammalian tumor and normal cells were investigated using rabbit antisera against amino and carboxyl terminal peptide fragments of G beta. A human nasopharyngeal carcinoma cell line (NPC TW039) was used as the cell model because of its short doubling time. RESULTS: Anti-G beta immunoreactivity was found to be associated with the plasma membrane and the mitotic spindle throughout the mitotic phase of cell replication. Colcemid pretreatment resulted in random distribution of the anti-G beta reaction product in the mitotic cells. The same phenomenon was also seen in various other tumor and normal cell lines. When solubilized membranous, cytosolic, and mitotic spindle fractions were analyzed by Western blotting, G beta (35 +/- 1 kDa) was found to be associated with the plasma membrane and mitotic spindle fractions. Immunoprecipitation of isolated mitotic spindles with anti-G beta further confirmed these results. CONCLUSIONS: These findings indicate that G beta is closely associated with the mitotic spindle as well as the plasma membrane and may be important in regulation of cell mitosis in addition to transmembrane signal transduction. PMID- 1460869 TI - Immunohistochemical and in situ hybridization studies of androgen receptor expression in a transplantable androgen-independent prostatic carcinoma line (AIT) of Noble rats. AB - BACKGROUND: In a previous study, we had shown that testosterone (T) administration to castrated Noble (NBL) rats, bearing an androgen-independent prostatic carcinoma line (AIT), caused a dramatic increase in high-affinity nuclear-androgen binding sites in the neoplasms. This increase in nuclear androgen receptors (AR) was accompanied by a transient doubling of the mitotic index in the tumors. EXPERIMENTAL DESIGN: In our current study we used immunohistochemistry and in situ hybridization to investigate the effects of androgen withdrawal and replacement on AR expression at the molecular/cellular level in the AIT. Results from immunohistochemical studies of AR expression in the AIT were compared with those from the prostates of intact, castrated, and castrated T-treated rats. RESULTS: Immunopositive staining for AR was found only in the nuclei of prostatic cells from the glands of intact, castrated or castrated T-treated animals. A few immunopositive tumor cells were present in AITs carried in untreated castrated hosts. In all instances, the reaction product was found in the cytoplasm, but it was also present in the nuclei of some tumor cells. Five days of T administration to castrated AIT-bearing rats caused a dramatic increase in immunopositive tumor cells. Nuclear staining was observed in all positive cells, but the reaction product was also present as well in the cytoplasm of some tumor cells. No differences in AR mRNA expression was detected by in situ hybridization studies of the AITs from castrated and castrated T treated rats. CONCLUSIONS: The differences in localization of AR between normal prostate and carcinoma cells may reflect alterations in DNA binding domains of the AR protein that occurred with neoplastic transformation. Our in situ findings suggest that unlike the normal prostate, where AR mRNA levels are autoregulated by androgen, AIT cells constitutively express these transcripts. Taken together, our findings suggest that the T-mediated increases in nuclear AR in the AIT, detected previously by binding assay and now by immunohistochemistry, are likely the result of post-transcriptional modifications in the receptor protein. PMID- 1460870 TI - Changes in antioxidant enzymes in isolated cardiac myocytes subjected to hypoxia reoxygenation. AB - BACKGROUND: Intracellular antioxidants have been shown to be depressed during hypoxia, and recovery upon reoxygenation has been correlated with the available antioxidant reserve. To test whether these antioxidant changes are also occurring at the cardiac myocytes level, we studied changes in antioxidant enzyme activities as well as cell injury in isolated cardiac myocytes exposed to hypoxia and reoxygenation. EXPERIMENTAL DESIGN: Isolated Ca(2+)-tolerant myocytes from adult male rats were subjected to 30 minutes hypoxia and 15 minutes reoxygenation. Antioxidant enzymes superoxide dismutase, glutathione peroxidase, catalase; lipid peroxide content; electrolytes (Na+, Ca2+); morphology; and high energy phosphates (ATP, ADP, AMP, creatinine phosphate) were studied in these myocytes. The effects of exogenous catalase (40 units/ml) on hypoxia reoxygenation induced changes in myocytes were also studied. RESULTS: Hypoxia resulted in a reduction in Mn superoxide dismutase and glutathione peroxidase activities with no change in CAT activity and malondialdehyde content. Reoxygenation of hypoxic cells resulted in recovery of Mn superoxide dismutase but not in glutathione peroxidase activity. Reoxygenation was without any effect on catalase activity, but a significant increase in the malondialdehyde content was seen. Hypoxia as well as reoxygenation caused a reduction in the number of rod-shaped cells with a parallel increase in hypercontracted as well as round cells. There was a significant increase in the myocyte Na+ and Ca2+ content during both hypoxia and reoxygenation, and this was accompanied by leakage of lactate dehydrogenase into the perfusion medium. These changes due to hypoxia and reoxygenation were significantly attenuated by addition of catalase (40 units/ml). High energy phosphates ATP, ADP, and AMP declined during hypoxia, and creatine phosphate was significantly reduced during reoxygenation. CONCLUSIONS: Hypoxia induces specific antioxidant changes in the isolated cardiac myocytes. Reduced ability to remove hydrogen peroxide appears to be an important determinant of myocyte injury during reoxygenation. PMID- 1460872 TI - Extracellular matrix-cell interaction: Matrigel and complex cellular pattern formation. PMID- 1460871 TI - Extracellular matrix-cell interactions: Matrigel and complex cellular pattern formation. PMID- 1460873 TI - Modelling coccidial infection in chickens: emphasis on vaccination by in-feed delivery of oocysts. AB - Trickle immunization of poultry by incorporating wildtype strains of coccidia in the feed has been shown to be an effective and practical means of controlling coccidiosis. Here we develop a mathematical model of the life cycle of Eimeria tenella and estimate the model parameters from extant experimental studies. Numerical solutions of the model compare well with experiment. The model provides quantitative estimates of the required trickle immunization hitherto only available after extensive time-consuming trials. PMID- 1460874 TI - A model of postnatal formation of alveoli in rat lung. AB - In rats, and many other species, most lung alveoli are formed after birth. Septation of the large air saccules existing at birth has been considered as the main mechanism for alveoli formation. However, other undefined means of alveolarization have also been postulated to account for the large increase in gas-exchange surface area that takes place in the lung as the rat grows larger. Moreover, recent results show that the majority of alveoli in rat lung are formed by means other than septation of saccules existing at birth, but these mechanisms have not been identified up to the present. In this study, a mathematical model of alveolarization in rat lung is presented. The model is based on three postulates: (a) new saccules continue to be formed up to adulthood according to certain rules; (b) all these saccules subsequently septate generating a certain number of alveoli; (c) once formed, the saccules (and alveoli) do not change in volume, but newly-formed saccules are larger than the preceding ones according to a given law. The model accurately predicts the experimentally-known values at different ages of total alveolar volume, alveolar number, volume of the average alveolus, gas-exchange surface area, and alveolar volume distribution for normal rats and for rats in which septation is inhibited by treatment with dexamethasone or hypoxia during the early postnatal weeks of life. PMID- 1460875 TI - Kin selection in density regulated populations. AB - The process of kin selection has both intra- and inter-group components (Hamilton, 1975, in: Biosocial Anthropology Wade, 1980). Group advantageous characteristics can evolve when inter-group differences in fertility are sufficiently great to overcome any within-group disadvantage of the trait. The potential magnitude of inter-group differences in fertility is determined largely by the way a population is regulated. Inter-group differences decrease as the spatial scale over which a population is regulated becomes increasingly localized. The present paper extends previous work by Boyd (1982, Anim. Behav. 30, 972-982) on the quantitative relation between kin selection and density regulation. A simple genetic model is employed to examine the conditions under which the interaction of local density regulation and kin selection can maintain a stable polymorphism. The ecological factors determining the spatial and temporal scale of density regulation are discussed. Finally, the results are applied to two biological cases in which local density regulation may be influencing the direction of phenotypic plasticity in group advantageous characters. PMID- 1460876 TI - Neurite branching pattern formation: modeling and computer simulation. AB - A model for nerve cell pattern formation is proposed in this paper. The model is based on some experimental results and an assumption that there is a kind of inhibitive interaction between growing neurites on the same nerve cell. In this paper, this interaction is termed lateral inhibition. A group of ordinary differential equations are used to describe the elongation of the terminal neurite segments of individual nerve cells. Computer simulation and comparison of it with in vitro studies are also made in this paper. PMID- 1460877 TI - [Thoracic radiography in Pneumocystis carinii pneumonia in AIDS patients. Presentation forms and clinical course]. AB - BACKGROUND: We intend to determine the frequency of the different radiographic findings of Pneumocystis carinii pneumonia in patients with AIDS. METHODS: We retrospectively review the chest roentgenograms of 30 patients at admission to the hospital (group I [n = 30]), at follow-up (group II [n = 30]) and after clinical recovery (group III [n = 15]). RESULTS: Diffuse bilateral interstitial disease was the most frequent radiographic finding at admission (76.6%) and at follow-up (60%). Atypical radiographic findings were: normal chest radiograph (group I [n = 3]), nodules (group I [n = 2], group II [n = 2], group III [n = 1]), thin wall cysts (group II [n = 1], group III [n = 1]), cavitated lesion (group II [n = 1], group III [n = 1]), pneumothorax (group II [n = 2], group III [n = 1]), pleural effusion (group III [n = 2]), asymmetrical distribution of the pulmonary lesion (group I [n = 2], group II [n = 3]) and predominant upper lobe involvement (group II [n = 1], group III [n = 1]). The atypical findings were greater during follow-up (group II [n = 33.3%], group III (46.6%) than at admission (group I [n = 23.4%]). CONCLUSIONS: It is important to know the frequency and multiplicity of the radiographic findings of Pneumocystis carinii pneumonia in order to establish the diagnosis and differentiation from other infectious diseases or other causes of pulmonary disease in patients with AIDS. PMID- 1460878 TI - [Treatment of gram negative bacilli bacteremia with intramuscular ceftriaxone in home care]. AB - BACKGROUND: Bacteremias by gram negative bacilli (BGNB) are serious diseases which normally require hospital admission. In accordance with the pharmacokinetic characteristics of ceftriaxone, the possibility of treating such processes with home care (HC) and the existence of advantages for both the patient and the hospital were evaluated. METHODS: Twenty patients were prospectively studied. Upon obtaining clinical stability in the hospital the possibility of following home care (HC) treatment was evaluated. Ceftriaxone was administrated at intramuscular doses of 1g/24 h. The clinical and bacteriologic response, patient satisfaction and treatment time were estimated. RESULTS: The origin of the bacteremia was varied as was the type of gram negative bacilli responsible. All the patients evolved favorably with no relevant secondary effects. The mean length of treatment was 12.75 days per patient. The antibiotic was mainly administered at home (83%), permitting a mean reduction of 10.5 hospital stays per patient. The social and psychologic advantages for the patients were evident. CONCLUSIONS: This study confirms the possibility of treating stable phase gram negative bacilli bacteremias at home efficiently with the supervision of home care teams leading to a substantial reduction in hospital expenses and patient satisfaction. PMID- 1460880 TI - [Hearing aids]. PMID- 1460879 TI - [Epidemiology, clinical course++, prognosis and treatment of thrombocytopenia associated with human immunodeficiency virus type 1 infection: analysis of 41 cases]. AB - BACKGROUND: Thrombocytopenia is one of the manifestations of infection by the human immunodeficiency virus-1 (HIV-1). A series of 41 patients were studied over a period of 2 years. METHODS: The study was prospectively carried out with a control group of 80 patients with the epidemiology, clinical manifestations, prognosis and treatment of this process being evaluated. RESULTS: The risk groups were: intravenous drug users (IVDU) (78%), homosexuals (12%) and heterosexuals (7%), patients with thrombocytopenia as the only manifestation (group IV-E) constituted the largest group with 30 cases. In 50% of the patients both diseases (thrombocytopenia and HIV infection) were simultaneously diagnosed. Nine patients (22%) vs 35% in the control group evolved to more advanced stages of the infection. Only 39% of the cases had hemorrhagic manifestations being more frequent in the IV-E group (47%) than in the remaining patients (18%). With regards to treatment, only 1 case responded completely with danazol. Steroids had variable, although evaluable, results with minimum secondary effects. The infusion of gammaglobulins achieved 80% of complete, although transitory, responses. Zidovudine obtained a positive response in 17/25 cases. Finally, splenectomy was performed in three patients definitively resolving the thrombocytopenia. CONCLUSIONS: In thrombocytopenia associated with human immunodeficiency virus-1 (HIV-1) infection the distribution by groups of risk is equal to that of the rest of infected patients. Appearing early in the natural history of HIV infection, thrombocytopenia presents few clinical manifestations and does not constitute a factor of bad prognosis. The treatment of choice is zidovudine at doses of 500 mg/day. PMID- 1460881 TI - [Paraneoplastic syndromes in medical and neurologic oncology]. PMID- 1460882 TI - [Still's disease in adults and polymyositis. An infrequent association]. AB - A case of coexistence of adult onset Still's disease and idiopathic inflammatory myopathy is reported in a patient with antecedent of Graves-Basedow disease. Although myalgias are common during the flares of adult onset Still's disease, a review of literature only disclosed two previous cases of polymyositis associated to adult onset Still's disease. A high index of suspicion is needed in order to diagnose such a rare association which has relevant prognostic and therapeutic implications. Treatment with methotrexate was started in order to control myopathy, resulting in improvement of both polymyositis and adult onset Still disease. A possible role of methotrexate in the management of adult onset Still's disease is suggested. PMID- 1460883 TI - [Regression of left ventricular hypertrophy in arterial hypertension. Are diuretics useful?]. PMID- 1460884 TI - [Diuretics and left ventricular hypertrophy]. PMID- 1460885 TI - [Hospital complications, their registration in the report of discharge and in the summary sheet of hospitalization]. PMID- 1460886 TI - [Multiple visceral hemorrhage as a result of thrombocytopenia induced by cloxacillin]. PMID- 1460887 TI - [The diagnosis of gout]. PMID- 1460888 TI - [Bronchodilators through tracheostomy]. PMID- 1460889 TI - [Chaos at the emergency service: several solutions]. PMID- 1460890 TI - [Usefulness of non-steroidal anti-inflammatory agents in the treatment of temporal arteritis]. PMID- 1460891 TI - [Usefulness of the determination of the mass concentration of creatine kinase 2]. PMID- 1460892 TI - [Dry syndrome and acquired immunodeficiency virus infection]. PMID- 1460893 TI - [Failure of antimalarial chemoprophylaxis in a traveler]. PMID- 1460894 TI - [Predictive factors of mortality in severe craniocerebral trauma]. AB - BACKGROUND: The prediction of mortality in severe head injury is of interest for the evaluation of patient prognosis and to also permit therapeutic measures to be considered and improve knowledge of this problem. METHODS: A multiple logistic regression model was developed and validated from the data obtained from a series of 231 patients hospitalized for the above mentioned condition. Seventy-five percent of the patients were used to define the model with the remaining 25% validating the same. RESULTS: The variables included in the model were: intraventricular hemorrhage, odds ratio = 20.4 (confidence interval 95%: 3.56 116); compression of basal cistern and/or of the III ventricle, odds ratio = 11.5 (4.43-29.8); mydriatic pupils in both eyes, odds ratio = 5.71 (1.32-24.6); age, odds ratio = 1.03 (1.01-1.05) and Glasgow scale upon admission, odds ratio = 0.57 (0.43-0.75). The maximum global value of the model (84.9%) corresponded to a sensitivity of 84.5% and specificity of 85.2%. The cut-off point of probability of death was found to be 0.475. In the validation of the model the highest global value (84.2%) was also observed at the cut-off point of 0.475 with a sensitivity of 84.2% and specificity of 84.4%. CONCLUSIONS: The predictive factors of mortality in severe head injury are the evidence of hemorrhage in the cerebral ventricles, mydriasis and a low score on the Glasgow scale. The model presented is useful and valid for carrying out the prediction of mortality at the time of admission and is also easy to apply since the variables used are obtained in the initial examination of the patients with severe head injury. PMID- 1460895 TI - [Experience with 150 subcutaneous venous reservoirs for venous access and infusion for the treatment of adult patients with oncologic and hematologic disorders and acquired immunodeficiency syndrome]. AB - BACKGROUND: In the present study the year experience of a multidisciplinary team (oncologic, unit for the acquired immunodeficiency syndrome, and surgery) with the use of a new method of central intravenous administration of medication such as that of subcutaneous venous reservoirs (SVR) is reviewed. METHODS: The subcutaneous injection capsules were implanted as a venous access in 150 surgical procedures in 146 patients from October 1985 to April 1991 with a total follow up of 29.190 days and a mean length of 251 days for SVR. Sixty-two percent (94 implantations) of the SVR were implanted in the out patient clinic, 20% (30 patients) were admitted for placement of the reservoir although this was only indicated in the first two years of the series, 13% (20 patients) during hospitalization for the base disease and only 4% (6 patients) were specifically admitted for surgical preparation (plasma, platelets, and others). SVR were used for chemotherapy (124 cases, 82%), repeated transfusions (6 cases, 4%) and chronic medication (acquired immunodeficiency syndrome, infections) (30 patients, 20%). Forty-two percent permitted chemotherapy administration by continual transfusion on an out patient regime. RESULTS: A series of mechanical complications (3 cases, 2%), septic (9 episodes in 7 patients, 5%) and thrombotic (8 of the catheter) (5%) and 4 of the central veins (2%) were observed. In the present series the rate of infections (5%) (0.072 episodes of bacteremia per 100 days/patient) and thrombosis (3%) was very low due to a strict protocol of maintenance and control by the medical team and hospital staff. The need for radiologic control during surgery is emphasized although, as demonstrated in the present review, the technique of localization by a cath-finder (external detector) permits greater speed with the same security. CONCLUSIONS: The degree of patient satisfaction and the minimum incidence of serious complications in determined risk groups (neutropenia, acquired immunodeficiency syndrome) demonstrates that subcutaneous venous reservoirs (SVR) constitute an excellent method as a chronic venous access. The SVR present a lower rate of complications if compared with any historic series of external vascular catheterization. PMID- 1460896 TI - [Factors associated with hypoalphalipoproteinemia]. AB - BACKGROUND: Hypoalphalipoproteinemia (HALP) is the most frequent lipid alteration found in patients with myocardial infarction at an early age. It is defined by amounts of lipid cholesterol at high density lipoproteins (cHDL) lower than 10% according to age and sex. The aim of this study was to know the frequency of main factors which reduce the levels of cHDL in a group of subjects with and without HALP. METHODS: Pathological antecedents, consumption of drugs, alcohol and cigarettes, the presence of obesity and levels of cholesterol, triglycerides, cHDL, glucose and urea were studied in a group of 1825 males. The study was performed in the course of medical examinations for workers. RESULTS: The consumption of cigarettes, the index of body mass (IBM) and the prevalence of diabetes mellitus were higher in the group of subjects with HALP. Hypertriglyceridemia (triglycerides > or = 200 mg/dl) was found in 31% of the subjects with HALP vs 10% in the control group (p < 0.001); hypocholesterolemia (cholesterol < or = 150 mg/dl) was also significantly greater (9.8% vs 4.3%, p < 0.01). Altogether, in 64% of the subjects with HALP, factors which may decrease cHDL were associated. Of the factors studied, the number of triglycerides, IBM and the number of cigarettes consumed per day were the independent factors which most significantly contributed to the decrease of cHDL in the regression analysis. CONCLUSIONS: Most of the subjects with hypoalphalipoproteinemia present other modifiable factors such as an elevated index of body mass, cigarette consumption and high amounts of triglicerydes, the correction of which constitutes the base for treatment of this disorder. PMID- 1460897 TI - [Influence of arterial pressure and plasma renin activity on tubular reabsorption of sodium]. AB - BACKGROUND: With the aim of confirming the possible existence of an increase in the fractional proximal reabsorption of sodium in the development of essential hypertension, the tubular dynamics of sodium were compared by the lithium clearance technique in a group of hypertensive patients and controls. METHODS: Following a week of drug suspension 186 patients with slight or moderate essential hypertension and 37 normal subjects with homogeneous sodium ingestion were studied. A clearing period of 90 minutes prior to the administration of a tracing doses of lithium was considered to calculate the fractional proximal and distal reabsorption of sodium in terms of glomerular filtration. In addition to global comparison of the measurements, the hypertensives were classified and compared according to mean arterial pressure (MAP) and percentages of plasma renin activity (PRA). RESULTS: No differences were found in tubular dynamics of sodium between hypertensive and normotensive patients. Neither did the degree of hypertension induce differences. However, upon classifying the patients according to PRA, it was found that those with PRA higher than 0.5 ng/ml-1/h-1 had less secondary natriuresis to a greater fractional distal reabsorption of sodium (p < 0.05). CONCLUSIONS: The findings of the this study do not support the possible existence of a primary defect of the transport of sodium in the proximal tubule in the origin and/or maintenance of essential arterial hypertension. PMID- 1460898 TI - [Prognosis in craniocerebral trauma]. PMID- 1460899 TI - [Cervicobrachial fibromatosis presenting in the mother and the child simultaneously]. AB - Fibromatosis is the proliferation of connective tissue with local infiltrative growth and a tendency to relapse in contrast with fibrosarcoma which never produces metastases. Two patients, a mother and son diagnosed with fibromatosis of initial cervical location in whom surgical extirpation and complementary radiotherapy were performed. The mother underwent polychemotherapy (adriamicine plus dacarbazine) because of extensive relapse. Definitive resolution was achieved in both cases. PMID- 1460900 TI - [Subcutaneous venous reservoirs]. PMID- 1460901 TI - [Aluminum in human pathology]. PMID- 1460903 TI - [The National Consensus for the Control of Tuberculosis in Spain]. PMID- 1460902 TI - [Stevens-Johnson syndrome induced by tetrabamate in a patient with HIV infection]. PMID- 1460904 TI - [Impact of the population over 75 years of age on a hospital for acute diseases]. PMID- 1460905 TI - [Mixed cryoglobulinemia associated with hepatitis C infection]. PMID- 1460906 TI - [Is it possible to reduce preoperatively the mortality of patients with ruptured aneurysm of the abdominal aorta?]. PMID- 1460907 TI - [Esophagopericardial fistula]. PMID- 1460908 TI - [Acute abdomen secondary to the administration of calcium channel blocker agents]. PMID- 1460909 TI - [Neutrophilic pleocytosis in brucella meningitis]. PMID- 1460910 TI - [Renal transplantation in children: punction-aspiration biopsy and renogram with 99mTc-DTPA]. AB - BACKGROUND: Renal transplantation in children raises numerous diagnostic problems. The renography obtained with diethyltriaminopentaacetic acid marked with (99mTc metastable technetium (99mTc-DTPA) was compared with fine needle aspiration biopsy (FNAB) in search of a better interpretation of post-transplant crisis: rejection, acute tubular necrosis, toxicity by cyclosporin A and infection. METHODS: Sixteen acute post-transplant episodes were studied in 13 children submitted to renal transplantation. The post-transplant time was 6 days to 2.5 years. The basal renography and FNAB were carried out following the initial clinical manifestations and over a period of less than one week. The vascular and renographic phases were evaluated by interpreting the renography and were compared to previous renographies. The diagnosis of the aspiration biopsy was expressed as: normal, acute tubular necrosis, total necrosis, toxicity by cyclosporin A, viral infection and rejection. RESULTS: Results agreed in 14 out of 16 cases: 1 normal, 3 acute tubular necrosis by renography and cellular necrosis by cytology, 9 rejections and 1 infection (increase in renal transit time). In the 2 cases with total necrosis of 100% followed by loss of renal allograft, the renographic diagnosis was severe vascular rejection with a negative prognosis. CONCLUSIONS: In this series FNAB confirmed the renography as useful in the early diagnosis of complications which may appear in children undergoing renal transplantation. PMID- 1460911 TI - [Psoas abscess: diagnostic and therapeutic usefulness of echography and computerized tomography]. AB - BACKGROUND: Psoas abscess (PA) is a clinically infrequent entity. The abscess may form spontaneously (primary PA) or as a complication of contiguous infection (secondary PA). The use of ultrasonography (US) and computerized tomography (CT) facilitates diagnosis and treatment of a disorder which previously required surgery. METHODS: Nineteen cases of PA diagnosed over the last 7 years were retrospectively studied. Confirmation of diagnosis was established by exteriorization of pus with US, CT or during surgery. RESULTS: Three primary PA (16%) and 16 secondary PA (84%) were diagnosed. The foci of origin of the secondary PA were: urologic (50%), rachydeal (25%), gastrointestinal (12.5%) and iatrogenic lumbar infection (12.5%). The most frequent germs in the primary PA were: Staphylococcus aureus (67%) and in the secondary PA, enterobacteriae (50%). The diagnostic profitability of US was 41% (7/17) and for CT was 100% (15/15). Percutaneous drainage was performed in 9 patients which failed in 2 cases due to compactness of pus (22%) and in another 2 because of undiagnosed osteomyelitis (22%). Two patients (10%) with underlying disease died despite adequate medical surgical treatment. CONCLUSIONS: Psoas abscess were secondary in 84% of the patients studied with most being due to enterobacteriae. The diagnostic profitability of computerized tomography was greater than that of ultrasonography (100% vs 41%). Percutaneous drainage is a valid therapeutic alternative. Relapse observed in this study was due to previously undiagnosed osteomyelitis. PMID- 1460912 TI - [Psychologic factors in chronic pain]. PMID- 1460913 TI - [Words of misleading translation in medical english]. PMID- 1460914 TI - [Systemic chronic candidiasis following typhlitis caused by Candida albicans]. AB - Typhlitis is an infrequent infectious complication which may appear during a period of intense granulocytopenia, generally in patients with acute leukemia. The most common causal germs are Gram negative bacilli although the importance of Candida sp. as an etiologic agent of this disease is ever more frequent. The case of a 14 years old patient with acute lymphoblastic leukemia who, after chemotherapy treatment, presented typhlitis by Candida albicans followed by chronic systemic candidiasis (CSC) is described. The role that Candida albicans may play in some cases of typhlitis is discussed as is the relation between the appearance of typhlitis and the posterior development of CSC. PMID- 1460915 TI - [Operative criteria for the prevention of alcoholism]. PMID- 1460916 TI - [Muscle cell cultures: current perspective]. PMID- 1460917 TI - [Cholestasis caused by captopril]. PMID- 1460918 TI - [Domiciliary nutrition support in pediatrics. Has its time come yet?]. PMID- 1460919 TI - [Toxoplasmosis and hepatitis]. PMID- 1460920 TI - [Doppler of the utero-ovarian artery in the differential diagnosis of ovarian tumors]. PMID- 1460921 TI - [Persistent suppurative meningitis]. PMID- 1460922 TI - [Rapid method for identifying Escherichia coli and species of the Proteeae tribe in urine]. AB - BACKGROUND: To evaluate the possibility of using the determination of beta glucuronidase and phenylalanine deaminase activity directly from urine samples for rapid detection (2 hours) of the presence of Escherichia coli and species of the Proteeae tribe. METHODS: To detect beta-glucuronidase activity methyl umbelipheryl-beta-D-glucuronic was used as a substrate. The presence of fluorescence after incubation at 37 degrees C for 2 hours indicated a positive reaction. While phenylalanine was used as a substrate for detecting phenylalanine deaminase activity, FeCl3 was added after incubation at 37 degrees C for 2 hours with a greenish color being observed indicating phenylalanine deaminase activity. RESULTS: The detection of Escherichia coli by beta-glucuronidase activity presented sensitivity and specificity of 0.91 and 0.99, respectively. The positive predictive value was 0.96 and the negative predictive value was 0.98, whereas the determination of the phenylalanine deaminase activity with the aim of detecting species of the Proteeae tribe presented the following results; sensitivity 0.92, specificity 0.99, positive predictive value 0.94 and negative predictive value 0.99. CONCLUSIONS: The determination of beta-glucuronidase and phenylalanine deaminase activities directly from urine sediment has been demonstrated as a rapid and specific test for detecting the presence of Escherichia coli and species of the Proteeae tribe, therefore it must be considered as a useful test in early diagnosis of urinary infection thereby facilitating the administration of appropriate antibiotic treatment. PMID- 1460923 TI - [Anti-endothelial cell antibodies in systemic lupus erythematosus: association with vascular and renal lesions]. AB - BACKGROUND: The aim of this study was to know the prevalence and characteristics of endothelial anticellular antibodies (EAA) in systemic lupus erythematosus and its relation with the clinical and immunologic manifestations of this entity. METHODS: A prospective study of 50 patients (44 females and 6 males) diagnosed with SLE was carried out. EAA and anticardiolipin antibodies (ACA) were determined by the ELISA technique, lupic anticoagulant by coagulometric techniques, antinuclear antibodies by indirect immunofluorescence, anti-DNA antibodies by the Farr technique, anti-ENA by contra-immunoelectrophoresis and the complement values by radial immunodiffusion. The statistical study was carried out by chi-square test and Fisher test. RESULTS: Positive titers of EAA were observed in 29 (58%) of the patients with SLE. The patients with EAA presented greater prevalence of both, vascular lesions (31% vs 5%, P < 0.05) and kidney involvement (62% vs 29%, p < 0.05) than those without EAA. Patients with EAA also presented a higher prevalence of antiphospholipid antibodies than patients without EAA (59% vs 10%, p < 0.001). No association was found between EAA and the titers of antinuclear antibodies, anti-DNA, anti-ENA or complement levels. CONCLUSIONS: Endothelial anticellular antibodies appear with greater frequency in patients with systemic lupus erythematosus and are more often associated with vascular and kidney involvement and with the detection of antiphospholipid antibodies suggesting that they may play an etiopathogenic role in the production of these lesions. PMID- 1460924 TI - [Low risk of acquiring the hepatitis C virus for the health personnel]. AB - BACKGROUND: The hepatitis C virus (HCV) is transmitted by the same routes as that of hepatitis B (HBV) and that of the human immunodeficiency virus (HIV). Health care workers have been considered at risk although of different intensity for acquiring the HBV and HIV with the risk of acquiring the HCV being ignored. METHODS: The presence of anti-HCV was investigated in 338 hospital workers, 110 proceeding from risk areas without direct contact with patients (laboratories and cleaning staff), 141 in direct contact and 87 with accidental risk (needle pricks or splashing of blood products) whom, at the time of the accident were anti-HCV negative. In the latter a minimum period of 6 months, which reached one year in 50% of the cases, elapsed to permit seroconversion. Three hundred seventy-seven healthy women were used as controls. The presence of anti-HCV was investigated with a second generation enzymoimmunoanalysis system confirming the results obtained with RIBA. RESULTS: The workers in zones of risk without direct patient contact presented global seroprevalence of anti-HCV of 1.8% with no statistical difference obtained between those who attended patients directly (1.4%) or the control group (2.1%). HCV transmission was not detected in any of the workers who experienced a high risk accident. CONCLUSIONS: The results concerning the study of the risk of health care workers to obtain hepatitis C suggest that the risk of transmission of the hepatitis C virus in these personnel is low. PMID- 1460925 TI - [Retrospective evaluation of the effectiveness of the BCG vaccine campaign in newborns of Barcelona]. AB - BACKGROUND: The aim of this study was to know the efficacy of the BCG vaccination campaign of the newborns of Barcelona carried out during the period from 1966 1974. METHODS: To achieve this aim an epidemiologic investigation was undertaken by an observational analytical study of paired cases and controls. Two hundred and fifty randomly selected cases were studied between 1978-1988 from between 4 21 years of age during the study period. The cases were paired with 750 controls (1:3) with identical conditions and age, sex and place of residence. Statistical analysis of data was performed by the specific methods for this type of study. RESULTS: The estimated gross odds ratio was 0.68; the interval of confidence 95% and 0.51-0.91 (p < 0.025). The efficacy of this vaccination campaign was estimated as weak at 32%, in the age group and investigation time being greater in males and diminished with time. The percentage of new cases of tuberculosis potentially prevented by this campaign was calculated at 13%. CONCLUSIONS: The weak efficacy of the BCG vaccination campaign may be attributed not only to the unforeseen effects of this vaccine but also to the deficient operative aspects of the campaign itself. PMID- 1460926 TI - [Time factors in bacteriologic diagnosis]. PMID- 1460927 TI - [Hypertension in diabetes mellitus. Role of calcium antagonists in its treatment]. PMID- 1460928 TI - [Immunoprophylaxis against hepatitis B]. PMID- 1460929 TI - [Dynamic pulmonary insufflation in critical illness]. PMID- 1460930 TI - [Analysis of a publication on the errors in the report of hospital discharge]. PMID- 1460931 TI - [Treatment of elderly patients with cancer]. PMID- 1460932 TI - [Intrafamilial transmission of HIV]. PMID- 1460933 TI - [Blood concentrations of cholesterol among school children of the Valle del Jerte (Caceres)]. PMID- 1460934 TI - [Skin metastasis of cancer of the lung in the Spanish literature]. PMID- 1460935 TI - [Insomnia in hospitalized patients]. PMID- 1460936 TI - [The evolution of mortality from ischemic heart disease in Basque Country 1975 1990]. AB - BACKGROUND: Given the importance of ischemic cardiopathy (IC) as a cause of death in industrialized countries, the trend of mortality by IC in people from 30 to 69 years of age residing in the Basque Country between 1975-1990 were studied. Furthermore, the evolution of the mortality by cardiac diseases and by other causes which may compete with IC in the certification or coding of the cause of death was studied. METHODS: The rate of mortality standardized by age by the direct methods were estimated from data from the Natural Movement of Population. The trend was graphically studied and quantified by means of the percentage difference between the rates. RESULTS: Mortality by IC decreased between 1975 1990 by 37% in men and 46% in women with a mean annual percentage decrease of 2.8% and 2.9%, respectively. Mortality by cardiac disease decreased 34% in men and 52% in women. CONCLUSIONS: Mortality by ischemic cardiopathy in the Basque Country has significantly decreased in both sexes. This decrease is not explicable by possible changes over the years in the practises of certification or coding of the cause of death. PMID- 1460937 TI - [Evolution of mortality from principal chronic diseases in Spain 1975-1988]. AB - BACKGROUND: Most mortality in developed countries is attributable to chronic non transmittable diseases, many of which are theoretically susceptible to prevention. The tendency of mortality by the principal chronic diseases in Spain is reviewed with different prevention strategies of the same being discussed. METHODS: The 9 chronic diseases which presented the highest mortality rate in Spain in 1988 are included. The rates of mortality, adjusted by age/year in males and females was calculated from the data of deaths by age, sex and cause of death from death statistics. Moreover, the percentage of the mean annual change of these during the periods 1975-1981 and 1982-1988 have also been calculated. RESULTS: Except for mortality by malignant tumor of the colon and rectum, malignant lung tumor in males and malignant breast tumors in women, which had an increase, the remaining diseases in the adjusted mortality rate by age decreased between 1975-1988. CONCLUSIONS: Among the diseases in which the rate of mortality has increased there is only that of malignant lung tumors for which one factor has consistently been identified as responsible for this increase, that being smoking. The possible influence of the control of arterial hypertension in the decrease in mortality of cerebrovascular disease must be emphasized. Moreover, the impact which the ninth review of the International Disease Classification had in the reduction in mortality by chronic bronchitis, emphysema and asthma must also be pointed out. PMID- 1460938 TI - [Incidence of hip fractures in Cantabria]. AB - BACKGROUND: Fracture of the hip constitutes a serious social/health care problem with very little information concerning incidence in Spain being available. METHODS: The diagnosis of hospital admissions and the diagnosis of release from the traumatology units of health care centers for acute patients in Cantabria were reviewed. The study was carried out from the 1st of January to the 31st of December 1988 and only included patients over 49 years of age. Patients who did not habitually reside in the region were excluded. The following data were collected in each case: age, sex, place of residence (urban or rural), time of the year, side fractured, type of injury, previous contralateral fracture and perioperative mortality. RESULTS: The rate of fracture referred to the population of more than 49 years of age was 277/100,000 in the case of females and 100/100,000 for males. The mean age of women was 80.4 +/- 8.5 years and of men was 76.9 +/- 10.9 years (p > 0.02), respectively. No differences were observed with regard to the place of residence or the time of year. The fracture was left sided in 61% of the females and 58% of the males. The injury was almost always due to a fall. Six percent of the patients had a previous contralateral fracture. Perioperative mortality was 6%. CONCLUSIONS: The incidence of hip fracture in Cantabria is similar to that of other regions in Spain and lower to that of parts of central and northern Europe and the United States. PMID- 1460939 TI - [Serologic diagnosis of Lyme disease in patients with undifferentiated arthritis. Diagnostic problems]. AB - BACKGROUND: Arthritis is a frequent manifestation of Lyme disease. The diagnosis of this disease is especially supported by serological techniques which however have false positives or negatives. The aim of this study was to establish the frequency of serologies positive to Borrelia burgdorferi in patients with non filiated arthritis and in other well defined rheumatic diseases. METHODS: A prospective study was performed to detect antibodies (AB) versus Borrelia burgdorferi in 43 patients with undifferentiated arthritis and in 100 patients with articular disease of precise diagnosis (rheumatoid arthritis, systemic lupus erythematosus, psoriasis arthropathy, and reactive arthritis/Reiter's syndrome). The technique was performed by indirect immunofluorescence and was repeated by enzymoimmunoassay in doubtful or positive results. Titers greater than 1/256 were considered as positive. RESULTS: Positive serology was found in two patients with undifferentiated arthritis and in one patient with Reiter's syndrome. None of the three patients referred the antecedent of erythema chronicum migrans. Positive serology was not observed in any of the patients with rheumatoid arthritis, systemic lupus erythematosus or psoriatic arthritis. CONCLUSIONS: A small proportion of patients with undifferentiated arthritis or Reiter's syndrome presented positive serology at low titers versus Borrelia burgdorferi with the interpretation of these results being difficult. The frequency of seropositivity in rheumatoid arthritis and systemic lupus erythematosus is very low. PMID- 1460940 TI - [Ten years of new criteria for the classification of systemic lupus erythematosus. Is everything clear?]. PMID- 1460941 TI - [Poisoning by delayed-release verapamil in an uremic patient]. AB - The appearance of toxic effects upon consumption of delayed release verapamil at therapeutic doses (120 mg/12 h) in a 64 year old patient with renal failure is described. The patient presented hypotension, bradycardia due to auriculoventricular block, hepatotoxicity, slight hyperglycemia, hyperpotassemia and metabolic acidosis with increased anionic gap. The picture remitted spontaneously with support treatment following discontinuation of the medication. The pathogenesis of the syndrome and the possibility that the hepatotoxicity was the triggering factor are discussed. Extreme precaution is recommended when this type of drugs is used in severe uremic or diabetic patients. PMID- 1460942 TI - [Inadequate demand in a pediatric hospital emergency department: factors involved]. AB - BACKGROUND: The massification of pediatric hospital emergency departments (PED) is due to bad use of the same by a large number of users. The causes related with this inadequate use have not been properly evaluated. METHODS: A sample representative of the population demanding medical care in a PED of a regional hospital was studied with the motives and sociodemographic and cultural factors presumably related with this inadequate demand being analyzed. RESULTS: 52% of the cases had had no previous contact with the primary level of health care and 79% had gone to the PED on their own initiative. With regard to consultations, 65.0 +/- 4.8% were catalogued as inadequate and a statistical relation was found with the age of the patient (less than one year), place of residence (urban) and the arrival by initiative of the patients themselves. CONCLUSIONS: Pediatric hospital emergency departments receive a high number of inadequate consultations at the second level of health care. The importance of the age of the patient, accessibility of pediatric hospital emergency departments and who takes the initiative to come must be emphasized as predictive variables of the bad use of these pediatric departments. PMID- 1460943 TI - [Critical review of the indication for diagnostic retrograde endoscopic cholangiopancreatography in the 90's (I)]. PMID- 1460944 TI - [Rhabdomyolysis associated with SC hemoglobinopathy]. PMID- 1460945 TI - [Tumor-related hypercalcemia. Considerations of the therapeutic and physiopathological aspects]. PMID- 1460946 TI - [Tetanus vaccination for adults since the establishment of primary health care facilities]. PMID- 1460947 TI - [Nosocomial infection by Xanthomonas maltophilia]. PMID- 1460948 TI - [Chylous ascites, chylothorax and cancer of the stomach]. PMID- 1460949 TI - [Delayed toxic myocardiopathy caused by adriamycin]. PMID- 1460950 TI - [Monoclonal antibodies in the treatment of septic shock]. PMID- 1460951 TI - [1992 medical language]. PMID- 1460952 TI - [Monoclonal antibodies in the treatment of sepsis and septic shock]. PMID- 1460953 TI - [Kaposi sarcoma following treatment of giant cell arteritis with corticoids]. PMID- 1460954 TI - [Increase in number of seizures following exposure to amoxycillin/clavulanic acid]. PMID- 1460955 TI - [Neurotoxicity and acyclovir]. PMID- 1460956 TI - [Neuralgic amyotrophy of the shoulder associated with systemic brucellosis]. PMID- 1460957 TI - [Some considerations concerning the search for Spanish studies in international databases]. PMID- 1460958 TI - [Early detection of colorectal cancer in the working medium]. PMID- 1460959 TI - [Pure sensory syndrome from cerebral hemorrhage]. PMID- 1460960 TI - [Early diagnosis of breast cancer]. PMID- 1460961 TI - [IgA Waldenstrom's macroglobulinemia?]. PMID- 1460962 TI - [Backache without objective findings should not be classified as occupational injury]. PMID- 1460963 TI - [How dangerous is exposure to loud music for early hearing damage?]. PMID- 1460964 TI - [ACE inhibitors and pregnancy]. PMID- 1460965 TI - [Cancer mutations and normal cell regulation]. PMID- 1460966 TI - [When "throats are visiting". Increased demands should be put on the rapid test]. PMID- 1460967 TI - [Do not forget economic interests as driving forces behind scientific fraud]. PMID- 1460968 TI - [Dynamic psychiatric approach helps to keep conflicts from being externalized]. PMID- 1460969 TI - [Exposure to noise by electronic amplified music--rock concerts carry a risk of hearing damage]. PMID- 1460970 TI - [Growing interest in the significance of personal attitude in traumatic stress]. PMID- 1460971 TI - [Conventional methods lead to faulty diagnosis of obscure proteinuria]. PMID- 1460972 TI - [The majority of visits to Statshalsan (State Occupational Health Services) are not related to work]. PMID- 1460973 TI - [Declining incidence of Chlamydia--increasing diagnostic demands]. PMID- 1460974 TI - [Myocardial infarction--important field for control of quality of health care and therapeutic results]. PMID- 1460975 TI - [An error concerning a neuroleptic]. PMID- 1460976 TI - [Ablation therapy with iodine radioisotopes as an alternative in hyperthyroidism]. PMID- 1460977 TI - [Cost-effectiveness of misoprostol prevention]. PMID- 1460978 TI - [Is it much more difficult to intubate in prone position?]. PMID- 1460979 TI - [Transient global amnesia--an obscure complaint with good prognosis]. PMID- 1460980 TI - [Sclerosing peritonitis--a rare but severe complication of peritoneal dialysis]. PMID- 1460981 TI - [A Swedish case of cholera with probable cause in a laboratory]. PMID- 1460982 TI - [Women with alcohol problems. Decreased need for psychological defense activity and decreased number of psychological problems after 2 years of treatment]. PMID- 1460983 TI - [Chlamydia trachomatis in young conscripts--survey, urine analysis and urethral culture]. PMID- 1460984 TI - [Working with sexual abuse experienced during childhood is easier using a theme]. PMID- 1460985 TI - [Difficulty in diagnosing total rupture of the Achilles tendon. Every 5th case is missed by the physicians involved in the initial treatment]. PMID- 1460986 TI - [A comparative study in Stockholm. Significant differences between hospitals in mortality among patients with acute myocardial infarction]. PMID- 1460987 TI - [Economics are widely discussed even in the Belgian health services]. PMID- 1460988 TI - [To observe and follow up or perform surgery in early prostatic cancer?]. PMID- 1460989 TI - [Human insulin and risk of hypoglycemia]. PMID- 1460990 TI - [Cervical manipulation--is it really justifiable?]. PMID- 1460991 TI - [No support by research that mercury causes mental symptoms]. PMID- 1460992 TI - [Study on incidence of Haemophilus influenzae type b. Factual incidence on a county level confirms earlier nationwide estimations]. PMID- 1460993 TI - [New pertussis vaccines are tested]. PMID- 1460994 TI - [Knowledge about effectiveness of general screening for prostatic cancer is limited]. PMID- 1460995 TI - [Urgent need for medical audit of activities at psychiatric outpatient clinics]. PMID- 1460996 TI - [The man behind the syndrome. Hieronymus von Munchhausen. A cavalry captain well known both in literature and in medicine]. PMID- 1460997 TI - [Severe effects of terfenadine overdose on the heart]. PMID- 1460998 TI - [Introducing a 2-month general sick leave benefit during pregnancy. An inexpensive reform would be of advantage to all parties]. PMID- 1461000 TI - [Medical and economic aspects of increasing antibiotic resistance]. PMID- 1460999 TI - [Transmission of Salmonella from chickens and eggs is increasing. Sweden is an exception]. PMID- 1461001 TI - [Pre-eclampsia--an endothelial disease of immunologic basis?]. PMID- 1461002 TI - [Follow the ALARA principle]. PMID- 1461003 TI - [Is there a basis for lowering of age limit in iodine-131 treatment of hyperthyroidism?]. PMID- 1461004 TI - [Complaints about video terminals depend mostly on work organization]. PMID- 1461005 TI - [Outpatient clinics, open during evening hours for consultation on skin changes, attracted many visitors]. PMID- 1461006 TI - [Medical psychology in medical education. More understanding, less excuses for emotional problems in the medical profession]. PMID- 1461007 TI - [Medical controversy at the Medical Society: can genetic diagnosis result in discrimination? Anxiety among geneticists, lack of interest in insurance companies]. PMID- 1461008 TI - [Substantial lowering of the limit for bacteriuria in lower urinary tract infections is unethical without sufficient documentation]. PMID- 1461010 TI - [Recommendations from a meeting of experts: treatment of acute and chronic heart failure]. PMID- 1461009 TI - [Cholera: transmission, treatment, prevention. The 1991 epidemic is the first one in this century in Latin America]. PMID- 1461011 TI - [Perianal streptococcal dermatitis is a possibility in therapy-resistant anal redness]. PMID- 1461012 TI - [When should a clinical trial be prematurely discontinued?]. PMID- 1461013 TI - [Need for stricter control of over-the-counter availability of rapid-diagnosis kits]. PMID- 1461014 TI - [It would be interesting to know the number of pregnant women choosing abortion]. PMID- 1461015 TI - [The views on the effect of breast cancer screening in younger women are ambivalent]. PMID- 1461016 TI - [Training in interview techniques is effective for both students and physicians]. PMID- 1461017 TI - [An inquiry shows minimal risk of hemorrhage resulting from thrombosis prevention in regional anesthesia]. PMID- 1461018 TI - [Bed rest after lumbar puncture is unnecessary and time-consuming]. PMID- 1461019 TI - [A new genetic technology makes the production of human monoclonal antibodies simpler]. AB - New advances in DNA technology have enabled repertoires of antibodies to be cloned and expressed in bacteria (E coli), thus creating libraries of antibody DNA. In principle, heavy and light chain DNA is amplified from lymphocyte RNA and combined into vectors that enable antibody molecules to be expressed on the surface of phage particles which carry the DNA for the corresponding antibody in their genomes. The system constitutes an ideal tool for use in selecting even rare antibodies from libraries of millions. The new advances have greatly facilitated the generation of monoclonal antibodies against various substances. In particular, human monoclonal antibodies are now more easily obtained with DNA technology than with the methods previously used. Many of the antibodies generated with the new techniques were derived from lymphocyte RNA from immune donors, though the isolation of specific antibodies from libraries originating from donors who have never been in contact with the particular antigens has recently been reported. Moreover, the binding characteristics of the immunoglobulins isolated have subsequently been enhanced in vitro. Thus, modern antibody cloning techniques give promise of allowing the generation of a wide range of specific antibodies from a single, diverse library of antibodies kept 'on the shelf' in the laboratory, without needing to immunise humans or animals. The impact on biomedical science is likely to be profound, as specific reagents for use in research or therapy will be easily obtained, irrespective of whether human or other mammalian antibodies are required. PMID- 1461020 TI - [The man and the woman behind the syndrome. A man and a woman behind the Cronkhite-Canada syndrome. A rare gastrointestinal polyposis with changes in the hair, skin and nails]. PMID- 1461021 TI - [Heart transplantations in Gothenburg--a review of the first 100 operations]. PMID- 1461023 TI - [SBU: magnetic resonance tomography is expensive. Cost effectiveness is still unclear]. PMID- 1461022 TI - [Thrombolytic treatment in wrongly diagnosed myocardial infarction]. PMID- 1461024 TI - [Market-oriented anesthesia--a threat or a possibility?]. PMID- 1461025 TI - [Certification of medical technicians]. PMID- 1461026 TI - [Weight reduction is beneficial]. PMID- 1461027 TI - [Primary health care and ambulatory psychiatric care. Diagnosis is the most important part in treatment of depression]. PMID- 1461028 TI - [Should we ignore any skin changes without taking measures?]. PMID- 1461029 TI - [Minimal risk of mix up when handling gases in laparoscopic surgery]. PMID- 1461030 TI - [Administration of antidepressants--comments to a therapeutic program]. PMID- 1461031 TI - [Board of Social Welfare, Institute for Public Health, Food Administration and Consumer Protection Department--what are all of you doing to control ineffective weight reducing products?]. PMID- 1461032 TI - [The first Swedish experiences: the umbrella is more considerate than surgery in patent ductus arteriosus]. PMID- 1461033 TI - [Shorter working periods at video display terminals may diminish symptoms of hypersensitivity to electricity]. PMID- 1461034 TI - [Cognitive therapy--a process of learning that changes dysfunctional thought patterns]. PMID- 1461035 TI - [Drug education in schools is increasing but many schools have none at all]. PMID- 1461036 TI - [Desmopressin--an effective agent in many hemorrhagic disorders]. PMID- 1461037 TI - [Hypercalcemia in lithium therapy--an underestimated complication?]. PMID- 1461038 TI - [Quality systems for emergency departments in the USA should be adopted by Swedish emergency care services]. PMID- 1461039 TI - [Endocarditis complicated by left ventricular pseudoaneurysm]. PMID- 1461040 TI - [Discussion and self-searching resulted in more effective care]. PMID- 1461041 TI - [Some advises to my house physician if I have one]. PMID- 1461042 TI - [The Soderberg prize to Per-Ingvar Branemark for osseointegrated implants]. PMID- 1461043 TI - [Good prognosis of brain infarction in young adults]. PMID- 1461044 TI - [Day surgery--the emperor's new clothes or solution of the economical crisis of surgery?]. PMID- 1461045 TI - [Serotonin and philosophy of life]. PMID- 1461046 TI - [Prognostic markers in reflux esophagitis better than wrapped up recommendations]. PMID- 1461047 TI - [Clozapine, a valuable contribution for the treatment of psychoses in Parkinson disease]. PMID- 1461048 TI - [Intraoperative angioscopy in infrainguinal in situ great saphenous vein bypass]. PMID- 1461049 TI - [Health and living conditions of female refugees must be improved]. PMID- 1461050 TI - [Alzheimer's disease--an amyloid disease of the brain]. AB - During recent years, Alzheimer's disease (AD) has attracted increasing interest among clinicians and neuropathologists throughout the world. The amyloid core of the neuritic plaques found in the brains of individuals with the disease has been shown to be composed of a distinct peptide formed through proteolytic degradation of a large precursor protein, the Alzheimer amyloid precursor protein (APP), which exists in at least three isoforms differing from each other in the splicing of the primary transcript from which they derive. Although the physiological function of APP remains unknown, it has been suggested to function as a protease inhibitor and to be important to the blood coagulation system. The gene encoding APP is located on the long arm of chromosome 21. Individuals with Down's syndrome (trisomy 21) often develop AD in early middle age, suggesting that the 50 percent increase in APP, gene expression may promote the development of the disease. Mutations in the APP gene have also been shown to be associated, probably pathogenetically with familial forms of AD. The conclusions drawn from these studies include (i) that the amyloidosis associated with AD is probably a central pathogenetic factor and (ii) that the development of drugs capable of inhibiting amyloidosis might be an appropriate strategy for the treatment of AD. PMID- 1461051 TI - [The National Board of Health and Welfare on breast implants: use saline protheses in the first place]. PMID- 1461053 TI - [Intravenous narcotic abuse necessitated vascular surgery]. PMID- 1461052 TI - [Paradoxical cerebral embolization in atrial septal defect]. PMID- 1461054 TI - [How is stomach ulcer transmitted? Epidemiology of Helicobacter pylori]. PMID- 1461055 TI - [Catheter ablation with radiofrequency current--a successful curative treatment of tachyarrhythmia]. PMID- 1461056 TI - [Tethered cervical spinal cord is a recently discovered clinical syndrome]. PMID- 1461057 TI - [Research on tumor cell immunogenicity: retroviral connection gives hope for more effective treatment of malignant gliomas]. PMID- 1461058 TI - [What is good care in hip arthroplasty?]. PMID- 1461059 TI - [Public opinion is positive towards autopsies--capital of confidence which should be administered better]. PMID- 1461060 TI - [Massive attention behind the National Society against Brain Diseases: the heart fund--the new basis for support of Swedish research of the nervous system]. PMID- 1461061 TI - [Treatment of basalioma--a still existing controversy]. PMID- 1461062 TI - [Undisputable information from a Swedish committee of experts: mammography reduces mortality of breast cancer. Benefits for the 40-49 age group are still not clear]. PMID- 1461063 TI - First Forum AMPERE, Rome, 1991: magnetic resonance imaging new methodologies: impact on industrial research. PMID- 1461064 TI - Magnetic resonance imaging: a new window into industrial processing. AB - Although the most important use of nuclear magnetic resonance imaging (MRI) continues to be for diagnostic medicine, recognition is being gained for many nonmedical applications. Examples include the following areas: petrogeology, food, agriculture, polymers and polymer-composites, and pharmaceuticals. These areas all involve studies of species that have short spin-spin relaxation times, and consequently need far fast gradient switching. These technical details are discussed and typical applications given. PMID- 1461065 TI - In vivo NMR in pharmaceutical research. AB - In vivo NMR techniques are currently well established in pharmaceutical research and will likely become increasingly important in the future, as they procure noninvasively morphological, physiological, and biochemical information. The status of magnetic resonance imaging (MRI) and spectroscopy (MRS) in drug development is discussed on the basis of the characterization and evaluation of a rat model of ischemic stroke and the development and profiling of drugs for cerebral ischemia in this model. It can be concluded that MRI is well suited for drug screening (quantitative determination of lesion size), while dynamic MRI and MRS techniques provide relevant information on the mechanism of drug actions. The possibility to follow changes, pathological and therapeutic, in the same individual is important from two points of view. First, variations due to interindividual differences may be eliminated, increasing the statistical power of the results. Second, dose and/or time dependence of a drug can be explored in the same individual. As a result, the number of animals required for a study will be reduced, which from both ethical and economic aspects is highly desirable. PMID- 1461066 TI - Spatially resolved NQR. AB - Pure nuclear quadrupole resonance (NQR) was combined with a rotating-frame imaging technique (rho NQRI). The method is suitable for powdery or crystalline materials containing quadrupole nuclei. The spatial information is encoded in the amplitudes of the free-induction decays (FIDs) by gradients of the radio frequency amplitude of the excitation pulse. The pulse length is incremented in a series of experiments so that a pseudo-FID can be formed from the intensities of a selected NQR line. A deconvolution procedure is used for the analysis of the pseudo-FIDs. The result is a sample profile along the gradient direction. The technique is particularly suitable for the detection of the spatial distribution of physical parameters producing NQR line shifts. Examples are stress or temperature. Two-dimensional images can be produced by rotating the sample step by step. For each orientation a profile across the sample is evaluated. A backprojection reconstruction formalism then permits the rendering of two dimensional NQR images. PMID- 1461067 TI - Magnetic resonance imaging: applications of novel methods in studies of porous media. AB - NMR imaging is finding broad applications in nonbiological areas including the study of fluid flow and fluid ingress in porous media. The porous media include at the one end mineral rocks and various building materials through various solid plastic materials to foodstuffs at the other end of the spectrum. The fluids within these various media range from crude oil and water mixtures, and water itself, to a range of organic solvents in plastic materials. This paper is concerned with the flow and ingress of water through Bentheimer sandstone and Ninian reservoir specimens, and also in solid nylon blocks. PMID- 1461069 TI - NMR imaging of solids with magic angle spinning. AB - Different aspects of solid state NMR imaging are reviewed, with emphasis on imaging in combination with line narrowing, especially in combination with magic angle spinning. Experimental results obtained with the latter technique are discussed, along with the implications of magic angle spinning on slice selection. PMID- 1461068 TI - Rapid line scan technique for artifact-free images of moving objects. AB - Moving objects (e.g., heart, lung, chest wall, etc.) typically cause artifacts to appear in two-dimensional Fourier transform ("spin warp") images. The rapid line scan (RLS) technique is a simple inexpensive technique that can rapidly produce artifact-free images of moving objects, without requiring enormous magnetic field gradients or periodic motions. The basic concepts and potential industrial applications of the RLS technique are described. PMID- 1461070 TI - Lee-Goldburg solid-state imaging. AB - A new approach to solid-state imaging (SSI) is presented. The method relies on narrowing the resonance line using the Lee-Goldburg sequence. The technique is easy to implement in practice and may find widespread applications in materials science. PMID- 1461071 TI - Partial cerebral ischemia assessed by "in vivo" 31P NMR spectroscopy in rats. AB - 31P NMR spectroscopy was used to assess the cerebral ischemia status in rats by measuring the relative levels of phosphate metabolites. Partial cerebral ischemia was induced in 49 rats by reversible occlusion of the carotid arteries. Rats were intubated and mechanically ventilated on a hypoxic gas mixture. Physiological parameters such as temperature and arterial pressure were strictly controlled during the experiments. 31P spectra were acquired at 7 T during basal observation, for 15-20 min after the induction of ischemia, and for 1 hr after reperfusion. Depletion and increase in PCr and Pi levels, respectively, were already observable in the collected spectra within few minutes after the onset of ischemia. No appreciable changes were found in the ATP levels. PMID- 1461072 TI - Magnetization filters: applications to NMR imaging of elastomers. AB - The general Fourier scheme for parameter selective imaging is subdivided into three periods: A preparation period for application of magnetization filters, an evolution period for space encoding, and a detection period for acquisition of the spectroscopic dimension. Depending on sample requirements and available time, the first and the last period can be omitted. Preparation of the initial magnetization for space encoding by appropriate filters is a powerful and time saving way to introduce parameter-selective image contrast. This is illustrated by filters of molecular dynamics, which are sensitive to segmental motion in different time windows for contrast enhancement in composite and aged elastomers. Further contrast amplification is achieved by computing the difference of images acquired with different filter settings. PMID- 1461073 TI - Multiple pulse NMR imaging of polymers and chemistry. AB - Multiple pulse line narrowing techniques can be used to improve resolution and sensitivity in solid state NMR imaging. For example, pulse sequences which remove homonuclear dipolar broadening have been used to image proton-containing materials. Further enhancements in resolution and sensitivity are obtained by removing inhomogeneous interactions such as chemical shift, susceptibility, and heteronuclear dipolar broadening. Pulse sequences have been designed which provide efficient line narrowing over large spectral widths by taking into account the experimenter's control over the amplitude and time dependence of the gradient-induced resonance offset. These methods have been applied to centimeter sized samples to obtain images of polymers, composite materials, and gas-solid chemical reactions. T1 and T2 contrast allows differentiation between materials. PMID- 1461074 TI - Proton spin lattice relaxation in aromatic polymers. AB - The most striking requirement for the NMR imaging of an object is that this object should be made with components having different NMR parameters. In most cases these parameters are due to the presence of a fluid and to its mobility, thus measurable parameters are proton signal intensity contrasted in T1 or T2. From the glass transition temperature Tg, by decreasing the temperature, all nonaromatic polymers as well as any well degassed polymers, show a continuous increase of their proton spin-lattice relaxation, which at low temperature is usually larger than 10-20 sec. However, due to O2 molecules selectively adsorbed on aromatic rings, non-degassed aromatic polymers show a marked shortening of the proton spin-lattice relaxation. This effect is maximal at rather low temperature, where T1 can be shorter than 1 msec, and in many known cases shorter than 500 msec. Since the amount of sorbed-O2 is a function of the chemical nature of the polymer, the type of crystallinity (polymorphism of semicrystalline polymers), the crystalline-amorphous ratio, and so on, a careful study of T1 relaxation as a function of the temperature can define optimal conditions for T1 contrast. Examples regarding polymorphism in syndiotactic polystyrene, butadiene-styrene block copolymers and blends, and poly(phenylene) oxide, will be discussed. PMID- 1461075 TI - Potential industrial applications of inhomogeneous broadening imaging. AB - Variations in magnetic susceptibility at air-water interfaces can result in inhomogeneous broadening of the NMR line. By special asymmetrical imaging techniques, originally developed for lung imaging, images can be formed of only those molecules that experience this inhomogeneous broadening. The basic concepts and latest developments in inhomogeneous-broadening-imaging techniques are described. Potential industrial applications are also discussed. PMID- 1461076 TI - Special-purpose MRI equipment for medical and industrial applications. AB - A brief survey of the permanent magnet design techniques that are made possible by the availability of modern magnetic materials is followed by experimental results and some consideration of their practical applicability to the realization of MRI magnets. PMID- 1461077 TI - Quantitative NMR imaging of multiphase flow in porous media. AB - Quantitative description of multiphase flow in porous media and local saturation distributions at steady states are of fundamental importance for petroleum recovery. The use of MRI provides an unprecedented means for obtaining such information. In this paper, profile imaging techniques for quantitative evaluation of fluid saturations during flow experiments in porous media are developed. The procedures for overcoming problems arising from very short, fluid saturation-dependent and spatial variation of T2, which are common in porous media, were addressed. The general methods developed should also be applicable to similar inhomogeneous biological systems. Experimental NMR imaging measurements of two-phase displacement were conducted in several limestones and sandstones representing various different types of pore structures, including a macroscopically homogeneous structure, a laminated structure, and a sample that exhibits porosity at different scales. The advantages of using each different type of profile imaging sequence to investigate flow in different types of porous structures are demonstrated. Images showing many features of multiphase flow, including nonuniform flow through different bedding structures, are obtained during the flow experiments. The use of profile images for obtaining many important petrophysical properties, such as permeability, porosity, saturation, and pore structural information, is discussed. PMID- 1461078 TI - Quantitative measurement and imaging of transport processes in plants and porous media by 1H NMR. AB - NMR and MRI have been applied to transport processes, that is, net flow and diffusion/perfusion, of water in whole plants, cells, and porous materials. By choosing proper time windows and pulse sequences, magnetic resonance imaging can be made selective for each of the two transport processes. For porous media and plant cells the evolution of the spatial distribution of excited spins has been determined by q-space imaging, using a 20 MHz pulsed 1H NMR imager. The results of these experiments are explained by including spin-relaxation and exchange at boundaries. A 10 MHz portable 1H NMR spectrometer is described, particularly suitable to study the response of net flow in plants and canopies to changing external conditions. PMID- 1461079 TI - Immiscible fluids permeability by T1 imaging. AB - Soil pollution by hydrocarbon compounds is an important part of the more general pollution problem. Some analogies with research problems encountered in studies of oil reservoirs in rocks suggested to us the opportunity to study the pollution dynamics by imaging the spatial distribution of the pollutant in a wet soil model by an NMR imaging technique. Some preliminary results using T1-weighted imaging are reported here. PMID- 1461080 TI - Diffusion and spatially resolved NMR in Berea and Venezuelan oil reservoir rocks. AB - Conventional and spatially resolved proton NMR and relaxation measurements are used in order to study the molecular motions and the equilibrium and nonequilibrium diffusion of oils in Berea sandstone and Venezuelan reservoir rocks. In the water-saturated Berea a single line with T*2 congruent to 150 microseconds is observed, while the relaxation recovery is multiexponential. In an oil reservoir rock (Ful 13) a single narrow line is present while a distribution of relaxation rates is evidenced from the recovery plots. On the contrary, in the Ful 7 sample (extracted at a deeper depth in a different zone) two NMR components are present, with 3.5 and 30 KHz linewidths, and the recovery plot exhibits biexponential law. No echo signal could be reconstructed in the oil reservoir rocks. These findings can be related to the effects in the micropores, where motions at very low frequency can occur in a thin layer. From a comparison of the diffusion constant in water-saturated Berea, D congruent to 5*10(-6) cm2/sec, with the ones in model systems, the average size of the pores is estimated around 40 A. The density profiles at the equilibrium show uniform distribution of oils or of water, and the relaxation rates appear independent from the selected slice. The nonequilibrium diffusion was studied as a function of time in a Berea cylinder with z axis along H0, starting from a thin layer of oil at the base, and detecting the spin density profiles d(z,t) with slice selection techniques. Simultaneously, the values of T1's were measured locally, and the distribution of the relaxation rates was observed to be present in any slice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461081 TI - Paramagnetic water proton relaxation enhancement: from contrast agents in MRI to reagents for quantitative "in vitro" assays. AB - The use of stable complexes of paramagnetic metal ions as probes in analytical applications of the NMR technique is discussed. Two examples are given that involve the determination of the total Fe3+ content of human serum transferrin (Tf) and the extent of glycation of human serum albumin (HSA). The method is based on the measurement of the longitudinal water proton relaxation times, conveniently altered following a selective chemical interaction between the substrate and the paramagnetic probe. PMID- 1461082 TI - Copper-D-penicillamine complex as potential contrast agent for MRI. AB - In vitro and in vivo proton T1 data are reported that demonstrate that the paramagnetic copper-D-penicillamine complex can be applied as a potential contrast agent to magnetic resonance imaging. PMID- 1461083 TI - Quantitative estimation of brain white matter abnormalities in elderly subjects using magnetic resonance imaging. AB - Twenty-five elderly subjects were examined with brain magnetic resonance imaging (MRI). The subjects were divided into two groups: those with Mini-Mental State Examination (MMSE) scores above 25, and those subjects with MMSE scores between 18 and 24. The degree of white matter abnormalities (WMA) (expressed as relative volumes) as well as the presence of cerebrovascular risk factors were evaluated in the two groups. We found that a) subjects with low MMSE scores had significantly larger relative volumes of WMA than the subjects with higher scores, b) a significant correlation (rs = 0.53, p < 0.009) between MMSE scores and the relative volume of WMA was also established, and c) a weak significant correlation (rs = -0.51, p < 0.05) between arterial blood pressure and WMA was found in the subjects with high MMSE scores. Besides these findings no other correlations between the presence of cerebrovascular risk factors and WMA were found in any of the groups. PMID- 1461084 TI - Identification of patients with hereditary haemochromatosis by magnetic resonance imaging and spectroscopic relaxation time measurements. AB - A total of 4302 healthy blood donors were screened for elevated serum ferritin and transferrin saturation. Fifteen had increased serum ferritin at a follow-up examination. Five relatives of these donors also entered the study. Eleven patients had elevated liver iron concentrations, while five had normal liver iron concentrations. The R2 relaxation rate in the liver was first measured with a conventional multi-spin-echo imaging sequence, and then by a volume-selective spectroscopic multi-spin-echo sequence, in order to achieve a minimum echo time of 4 msec. No correlation was found between the relaxation rate R2 and the liver iron concentration, when R2 was calculated from the imaging data. Multi exponential transverse relaxation could be resolved when the spectroscopic sequence was used. A strong correlation between the initial slope of the relaxation curve and the liver iron concentration was found (r = 0.90, p < 0.001). Signal intensity ratios between liver and muscle were calculated from the first three echoes in the multi-echo imaging sequence, and from a gradient echo sequence. A strong correlation between the logarithm of the signal intensity ratios and the liver iron concentration was found. Although both spectroscopic T2 relaxation time measurements and signal intensity ratios could be used to quantify liver iron concentration, the gradient echo imaging seemed to be the best choice. Gradient echo imaging could be performed during a single breath hold, so motion artifacts could be avoided. The accuracy of liver iron concentration estimates from signal intensity ratios in the gradient echo images was about 35%. PMID- 1461085 TI - Cine MR voiding cystourethrogram in adult normal males. AB - Cine voiding cystourethrogram was performed in 15 normal subjects using T1 weighted Turbo FLASH sequence. It showed the sequence of emptying of bladder, detrusor muscle contraction, opening of the sphincters, and various parts of urethra. It was found to be a good noninvasive test to study the dynamics of lower urinary tract without disturbing the state of the physiology. PMID- 1461086 TI - Outflow refreshment angiography: a bright blood, bright static tissue technique. AB - A new "bright blood" strategy, outflow refreshment imaging, is introduced in which a number of overlapping slices are excited in rapid succession. Flowing spins that refresh each overlapped slice portion contribute a bright signal. Additionally, static tissue in each non-overlapped slice portion also yields a bright signal. However, the flow/static contrast is comparable to that produced in inflow refreshment images, and angiograms can be generated by conventional maximum intensity projection processing. The dual ability to visualize angiograms and static tissue images is a major benefit of the strategy. Computer simulations of flow sensitivities and in vivo results are presented which compare the outflow and inflow refreshment imaging strategies. PMID- 1461087 TI - Magnetic resonance imaging and pulsed Doppler sonography of poststenotic jets: correlation between signal void and flow velocity distribution. AB - To correlate the appearance of poststenotic jets on gradient echo images with features of localized Doppler spectra of the jets, we studied an in vitro model of steady flow-through stenoses of 86, 96, and 99% area reduction. As fluids, water and a 40% glycerol solution in water were used. MRI was performed with a 1.5 T whole body imager and gradient echo images were obtained in planes parallel to the direction of flow. Doppler spectra were acquired separately from the MR measurements at 1 cm intervals for a distance of 10 cm downstream from the stenosis. Poststenotic signal void was observed for water and for the 40% glycerol solution only if the mean velocity within the stenosis exceeded a limit of 50-60 cm/sec. On the MR images, the jets could be divided into two segments: A proximal jet segment of uniform width equal to the diameter of the stenosis, followed by a distal jet segment which was characterized by broadening and then dissipating signal void. Except for the 99% stenosis, a high signal intensity core was present within the proximal jet segment. In the proximal jet segment, the Doppler measurements showed a low temporal fluctuation of the maximal flow velocity and only little flow opposite to the main flow direction. In the distal jet segment, the velocity fluctuation and the intensity of reverse flow increased sharply. The high signal intensity core of the jet was associated with a poststenotic zone of constant maximal flow velocity. The results demonstrate a close relationship between characteristic features of poststenotic jets in MRI and pulsed Doppler sonography. PMID- 1461088 TI - Evaluation of two new gadolinium chelates as contrast agents for MRI. AB - Two new gadolinium chelates were investigated for potential use as tissue specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N''-bis(3-hydroxy-6-methyl-2- pyridylmethyl)diethylenetriamine N,N',N''-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7,13-triaza-4,10,16 trioxacyclooctadecane-N,N', N''-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T1-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney. PMID- 1461090 TI - Surface coil imaging of rat spine at 7.0 T. AB - An inductively coupled surface coil for imaging the rat spine at 7 T is described. This planar circular probe was made from microwave substrate to limit the size of the coil and to minimize the magnetic susceptibility. The surface coil was used as a single transmit/receive coil and as a receive-only coil with a birdcage body coil for excitation. The signal-to-noise ratio (SNR) of the probe was compared to a 5-cm birdcage coil and exceeded the birdcage coil's SNR by three to six times at superficial structures. The main advantages of the probe are an improved SNR for superficial structures and a simple design and use. Images with 50 x 50 x 500 micron voxels were obtained of the rat spine with excellent anatomical detail. PMID- 1461089 TI - MRI contrast-dose relationship of manganese(III)tetra(4-sulfonatophenyl) porphyrin with human xenograft tumors in nude mice at 2.0 T. AB - Previously we reported that Mn(III)tetra(4-sulfonatophenyl) porphyrin, MnTPPS4, is a contrast agent which can effectively enhance tumor detection by MRI. By imaging 30 additional athymic nude mice bearing subcutaneous MCF-7 WT human breast carcinoma xenografts, we have extended dose-contrast relationships over a wide range of intraperitoneal (IP) doses ranging from 0.025 to 0.50 mmol/kg. The benefits of IP injection are higher possible doses on a volume basis and a reduction in toxicity versus IV administration. Full coronal cross-section images have been obtained on a 2-T spectrometer. Although individual tumor masses displayed different distribution patterns, reflective of their internal morphology, single doses of 0.10 mmol/kg or greater were necessary to produce a detectable effect. At a dose of 0.50 mmol/kg, marked enhancement was produced. Multiple small dosages administered over the course of several days before imaging did not produce increased enhancement. Preliminary results on the new porphyrin derivative, MnTPPS3, indicate that the ratio of the toxic dose to the effective dose may be adjustable to render this class of agents clinically useful. PMID- 1461091 TI - In vivo NMR T2 relaxation of experimental brain tumors in the cat: a multiparameter tissue characterization. AB - Experimental gliomas (F98) were inoculated in cat brain for the systematic study of their in vivo T2 relaxation time behavior. With a CPMG multi-echo imaging sequence, a train of 16 echoes was evaluated to obtain the transverse relaxation time and the magnetization M(0) at time t = 0. The magnetization decay curves were analyzed for biexponentiality. All tissues showed monoexponential T2, only that of the ventricular fluid and part of the vital tumor tissue were biexponential. Based on these NMR relaxation parameters the tissues were characterized, their correct assignment being assured by comparison with histological slices. T2 of normal grey and white matter was 74 +/- 6 and 72 +/- 6 msec, respectively. These two tissue types were distinguished through M(0) which for white matter was only 0.88 of the intensity of grey matter in full agreement with water content, determined from tissue specimens. At the time of maximal tumor growth and edema spread a tissue differentiation was possible in NMR relaxation parameter images. Separation of the three tissue groups of normal tissue, tumor and edema was based on T2 with T2(normal) < T2(tumor) < T2(edema). Using M(0) as a second parameter the differentiation was supported, in particular between white matter and tumor or edema. Animals were studied at 1-4 wk after tumor implantation to study tumor development. The magnetization M(0) of both tumor and peritumoral edema went through a maximum between the second and third week of tumor growth. T2 of edema was maximal at the same time with 133 +/- 4 msec, while the relaxation time of tumor continued to increase during the whole growth period, reaching values of 114 +/- 12 msec at the fourth week. Thus, a complete characterization of pathological tissues with NMR relaxometry must include a detailed study of the developmental changes of these tissues to assure correct experimental conditions for the goal of optimal contrast between normal and pathological regions in the NMR images. PMID- 1461092 TI - A study of T1-weighted 31phosphorus MR-spectroscopy from patients with focal and diffuse liver disease. AB - 31P-MR-Spectroscopy was performed in 28 patients with focal (n = 23) and diffuse (n = 5) liver disease and in 18 healthy volunteers. The spectra were obtained with a whole body scanner operating at 1.5 T by using a surface coil. To get T1 weighted 31P-spectra a short TR of 600 msec was taken, because T1-weighted spectra of focal liver disease were more significantly different from spectra from healthy volunteers than density weighted ones. The VOI from patients with focal superficial alterations showed a mean volume of 172 ml, with diffuse liver disease 196 ml, and from volunteers 158 ml. Focal tumors filled up the VOI on an average of 70%. This investigation demonstrated that PME/beta-ATP- and PDE/beta ATP-ratios were sensitive indicators for focal liver disease. As a result of this study we could establish a significant increase of PME/beta-ATP- (0.75 +/- 0.30) and PDE/beta-ATP-ratios (1.68 +/- 0.62) in patients with superficial focal liver metastases (n = 19) compared to the control group (PME/beta-ATP: 0.49 +/- 0.17, PDE/beta-ATP: 1.24 +/- 0.24; t-test: p < 0.02). Patients with a hemangioma (n = 1), liver infarction (n = 1), empyema of gallbladder (n = 1) and a hepatic involvement by a malignant lymphoma (n = 1) showed a similar increase of PME/beta ATP and/or PDE/beta-ATP. Up to now spectral changes seemed to be non-specific. The ratios of 31P metabolites of the cirrhoses (n = 4) and the fatty liver (n = 1) did not show any characteristic changes versus the volunteers. PMID- 1461093 TI - Localized in vivo 1H spectroscopy of human skeletal muscle: normal and pathologic findings. AB - To obtain high signal to noise ratio in small volume elements (8 cm3), in vivo 1H NMR spectroscopy of normal and diseased human skeletal muscle was performed using a double spin-echo localization method on a 1.5-T whole body system. High resolved spectra of normal calf muscle show the well known resonances of lipids (methyl, methylene, olefinic, and other fatty acid resonances), creatine/phosphocreatine, choline/carnitine, taurine, and histidine with good intraindividual reproducibility. Pronounced intraindividual differences in the lipid range were found between different upper thigh muscle groups. On pathologic conditions like myopathy, myositis or irradiation damage the spectral lipid content was increased. Three months after local irradiation of the medial vastus muscle (50 Gy), the localized 1H NMR spectrum showed a complete loss of the choline and creatine signals. In a case of M. Behcet with muscular involvement the relative reduction of the choline signal may provide an insight in the pathobiochemistry. The results of our investigations in nine healthy volunteers and three patients are presented in detail including relaxation times of the metabolites. PMID- 1461094 TI - Three-dimensional 1H spectroscopic imaging of cerebral metabolites in the rat using surface coils. AB - Three dimensional metabolite maps of protonated metabolites were obtained using 1H magnetic resonance spectroscopic imaging at 7 T. Surface coils were used to increase sensitivity and spatial resolution significantly over a volume coil two dimensional acquisition. Adiabatic pulses were employed to provide homogeneous B1 excitation and frequency selective refocusing over the volume of the rat brain. These techniques were employed to obtain three-dimensional spectroscopic imaging spectra from nominal voxel volumes of 9-30 microliters from rat brain. The improved spatial resolution and sensitivity are also demonstrated with studies of focal ischemia in the rat. PMID- 1461095 TI - Noninvasive in vivo 13C-NMR spectroscopy of a 13C-labeled xenobiotic in the rat. AB - This study demonstrates that the xenobiotic product, 1-(o-chlorophenyl)-1-(p chlorophenyl)-2,2-dichloro-3-13C-propane can be monitored in the liver of an intact animal by in vivo 13C surface coil NMR spectroscopy after intraperitoneal administration. The carbon-13 label could be detected after a single dose of only 200 mg/kg of the product. The intrahepatic changes of the signal intensity of the labeled product were monitored as a function of time. No signals corresponding to metabolites could be detected. PMID- 1461096 TI - In vivo relaxation of N-acetyl-aspartate, creatine plus phosphocreatine, and choline containing compounds during the course of brain infarction: a proton MRS study. AB - Localized water suppressed proton spectroscopy has opened up a new field of pathophysiological studies of severe brain ischemia. The signals obtained with the pulse sequences used so far are both T1 and T2 weighted. In order to evaluate the extent to which changes in metabolite signals during the course of infarction can be explained by changes in T1 and T2 relaxation times, eight patients with acute stroke were studied. STEAM sequences with varying echo delay times and repetition times were used to measure T1 and T2 of N-acetyl-aspartate (NAA), creatine plus phosphocreatine (Cr+PCr) and choline containing compounds (CHO) in a 27-ml voxel located in the affected area of the brain. Ten healthy volunteers served as controls. We found no difference in T1 or T2 of the metabolites between the patients and the normal controls. The T2 of CHO was longer than that of NAA and Cr+PCr. Our results indicate that spectra obtained in brain infarcts and normal tissue with the same acquisition parameters are directly comparable with respect to relative signal intensities as well as signals scaled with internal and external standards. PMID- 1461097 TI - Tissue characterization by image processing subtraction: windowing of specific T1 values. AB - A method for windowing specific T1 values is presented. A 1.0 T imager with two routine pulse sequences was employed: A T1-weighted spin echo (SE) sequence and a short tau inversion recovery STIR sequence (fat-suppressed IR). A T1 window for fat was obtained by subtracting the STIR image from the SE image. Negative values were coded black. The method was tested on a normal human thigh, on a human liver with confirmed fatty infiltration, and on the livers of four live burbots. The fat-containing tissues of the two human volunteers were well depicted. The differences in fat concentration among the burbot livers were also clearly shown. The fat intensity seen in the images correlated well with the chemically measured fat concentration. This subtraction method for windowing T1 values proved feasible for fat. The method could be used for tissues with other short T1 values as well. PMID- 1461098 TI - MR of an adrenal pseudocyst. AB - We describe the appearance of an adrenal pseudocyst on MRI and CT. The MR characteristics of the lesion were noteworthy in that the lesion had two components with different imaging characteristics. The larger component was of low signal intensity on both T1- and T2-weighted images and might have been confused with an adrenal adenoma. PMID- 1461099 TI - A 19-month-old child with cough, stridor, fever, respiratory distress, and seizures. PMID- 1461100 TI - Imaging case of the month. Congenital cystic adenomatoid malformation of the lung, type III. PMID- 1461101 TI - Management of type I diabetes for children in school. PMID- 1461102 TI - Frank A. Gunther, Jr., chairperson of the Board of Directors of Blue Cross and Blue Shield of Maryland--an interview with the editor. Interview by Victor R. Hrehorovich. PMID- 1461104 TI - Functional improvement in geriatric trauma patients admitted to a dedicated rehabilitation hospital. AB - A retrospective study was undertaken of trauma patients over 55 years of age who were admitted to a rehabilitation hospital during an 18-month period. Significant risk factors for poorer in-hospital improvement in functional independent measures were male sex, having an offspring listed as next of kin, pre-injury diabetes mellitus and/or dementia, and number of co-morbidities. Being married was found to be protective. PMID- 1461103 TI - Physician estimates of substance abuse in Baltimore and Cumberland: 1991. AB - By identifying and counseling substance abusers within their own practices, primary care physicians can play a major role in reducing levels of substance abuse. How proficient area physicians are in identifying substance abuse is examined by comparing physician estimates of substance abuse in their patient populations with local and national statistics. PMID- 1461105 TI - Ophthalmomyiasis externa: a case report. AB - A three-year-old white male presented with an extremely painful abscess of the nasal portion of the right upper eyelid. A larva identified as family Cuterebridae, genus Cuterebra sp, was removed from the abscess, permitting its rapid resolution. This represents an unusual patient with external ophthalmomyiasis who enjoys excellent nutritional and environmental surroundings. PMID- 1461106 TI - Two centuries of medical organization and licensure in Maryland. AB - In 1766, the first American medical society was established in New Jersey. It was not until 1968, more than 200 years later, that the state medical societies would finally mold a satisfactory means of medical qualification and licensure. PMID- 1461107 TI - Sir William Osler--contrasts between the saint-like legend and the rough-edged man. AB - Sir William Osler, the first physician-in-chief of the Johns Hopkins Hospital and later Regius Professor of Medicine at Oxford, is judged by many to be the greatest clinician of the modern era. His life history of distinguished service to medicine and to society is well known. What is not so well known is his mischievous streak. PMID- 1461108 TI - T1 snapshot FLASH measurement of rat brain glioma: kinetics of the tumor enhancing contrast agent manganese (III) tetraphenylporphine sulfonate. AB - The ultrafast inversion recovery snapshot FLASH technique was used to determine the kinetics of the contrast agent manganese (III) tetraphenylporphine sulfonate (MnTPPS) in experimental brain tumors in rats. In the first part of the investigation this technique was validated with the conventional inversion recovery spin-echo method by comparing in vivo T1 data of a normal rat brain. Agreement between T1 values obtained from both techniques was complete, as tested for a large number of pixels in identical coronal slices. In the second part the fast IR snapshot FLASH method was applied to study the effect of the NMR contrast agent MnTPPS on the T1 relaxation time of experimental gliomas in rat brains. T1 of normal brain tissue (1024-1035 ms), tumor (1217 ms), and edema (1199 ms) was determined with the inversion recovery version of the snapshot FLASH imaging technique. After intraperitoneal injection of MnTPPS (0.25 mmol/kg body wt) T1 decreased exponentially to 56% of control in tumor and to 62% in muscle. In normal and edematous brain tissue no significant changes in T1 were observed up to 5 h after injection of the contrast agent. Once the T1 contrast between tumor and peritumoral brain tissue had reached a saturation, the enhancement persisted for several hours to days. Therefore application of this contrast agent resulted in a sharp demarcation between glioma and peri-tumoral edema. PMID- 1461109 TI - Nuclear magnetic resonance velocity spectra of pulsatile flow in a rigid tube. AB - Velocity spectra can be derived from velocity-encoded nuclear magnetic resonance (NMR) images. Velocity spectra are histograms showing the amounts of fluid flowing at different velocities in the sensitive volume of the measurement. Velocity spectra may prove to be useful in characterizing the flow of blood in small vessels, for example, in detecting the presence of stenoses and in evaluating their severity. NMR velocity spectra acquired in vivo are sufficiently complicated that a model system was designed and tested to investigate the velocity spectra of pulsatile flow. This study measured the NMR velocity spectra of pulsatile flow in a rigid tube and compared them to velocity spectra derived from Doppler ultrasound measurements and to velocity spectra inferred from a theoretical model driven by the measured pressure difference function. The experimental results from each technique agree. PMID- 1461110 TI - Tissue characterization and assessment of preoperative chemotherapeutic response in musculoskeletal tumors by in vivo 31P magnetic resonance spectroscopy. AB - This study investigates the potential of in vivo 31P magnetic resonance spectroscopy (MRS) to characterize musculoskeletal tumors and to determine preoperative levels of histological necrosis, which is an important clinical indicator of patient response. Pretherapy MRS was performed on 28 patients with large musculoskeletal tumors: 13 with osteosarcoma, 3 with chondrosarcoma, 5 with malignant fibrous histiocytoma, 1 with desmoid tumor, 1 with Ewing's, 2 with hemangioendothelioma, 1 with myxoid liposarcoma, 1 with synovial cell sarcoma, and 1 with rhabdomyosarcoma. Fifteen patients had follow-up MRS examinations after commencement of chemotherapy (mean of five/patient), eight of whom have now had surgery. Elevated levels of PMEs (P < 0.01), P(i) (P < 0.01), and PDEs (P < 0.02) as well as elevated tumor pH (P < 0.05) were observed in all patients. The synovial cell sarcoma was characterized by high levels of PMEs (> 20%) and low pH (pH 6.76). This contrasted with the spectra obtained from the malignant fibrous histiocytomas which had high levels of PDEs (17 +/- 5%). Reductions in PDE levels postchemotherapy were associated with a high degree of necrosis (> 90%) at surgery, while an increase in PDE levels was associated with a low level of histological necrosis. Likewise, reductions in the ratios PDE/NTP and PDE/PCr and an increase in P(i)/PDE were also associated with a high level of necrosis. PMID- 1461111 TI - Spin-echo M-mode NMR imaging. AB - A nuclear magnetic resonance (NMR) imaging and display method for the observation of the continuous motion of objects is presented. By modifying a line scan technique, the spin-density distribution along a line is displayed in succession. Although spatial information is limited to only one dimension, the motion of the object is recorded at intervals of 55 ms by using a commercially available NMR imaging system. In a phantom study, this method yielded accurate velocity measurements along a single axis. When the method was applied to the human chest, an image analogous to that of M-mode echocardiography was obtained. This method, which can be called spin-echo M-mode NMR imaging, approaches the functional analysis of cardiac wall motion in regions where echocardiography is not possible. The effects of respiratory motion on the left ventricular wall were recorded in addition to its intrinsic contractile motion in an image obtained along a line parallel to the cranio-caudal axis of the body. The advantages of this method to assess cardiac wall motion in a patient with an arrhythmia were also demonstrated. PMID- 1461112 TI - Signal-to-noise, resolution, and bias function analysis of asymmetric sampling with zero-padded magnitude FT reconstruction. AB - This report describes NMR image effects due to sampling asymmetry when using zero padded magnitude FT reconstruction. With this method, the MTF is not flat over the spatial frequency passband, so resolution cannot be accurately described by a single variable such as voxel size. At small to moderate asymmetry, shortened (reduced window duration) asymmetry provides increased S/N and decreased resolution, whereas shifted (constant window duration) asymmetry yields essentially constant S/N with simultaneously increased and decreased resolution. A bias function expression describes image distortion due to sampling in terms separable from the imaged object. The analyses are consistent with previous descriptions of perceived image differences related to data asymmetry. PMID- 1461113 TI - Characteristics of extracellular sodium relaxation in perfused hearts with pathologic interventions. AB - Sodium spectroscopy and imaging sequences designed to emphasize fast T2 decay or the multiple quantum signal have previously demonstrated a high contrast between normal and pathologic tissue which may be due to changes in intracellular versus extracellular sodium distribution. Since alterations in the amount of signal with fast T2 decay have previously been shown to occur with changes in intracellular sodium content, this study investigated the fast T2 relaxation characteristics of extracellular sodium during pathologic interventions on nonsubmerged perfused rat hearts. T2 data on total sodium content were obtained while global ischemia (stopping all perfusate flow) and extracellular edema (due to long perfusion times) were induced in the heart. The data were fit to a biexponential, with Mf(T2f) the magnitude (time constant) of the fast component of decay. Mf increased significantly in both pathologies (to 319 +/- 26%, n = 3, of baseline for ischemia and to 527 +/- 284%, n = 3, of baseline for edema); the increase with edema was demonstrated to be due to extracellular sodium by intermittently perfusing the heart for a short period with shift reagent. When shift reagent was not used until the conclusion of the edema experiment, Mf increased to 169 +/- 35% of baseline, also due mainly to extracellular sodium. T2f did not exhibit any trends with these experiments, with values ranging from 1.7 to 5.5 ms. We believe that these results indicate that compartmental sodium content will most likely not be quantifiable in pathologic states in the heart with relaxation-based techniques. However, correlations between the pathologic state of the tissue and the sodium NMR signal obtained with pulse sequences or images that emphasize a particular aspect of relaxation may prove to be useful. PMID- 1461114 TI - 31P NMR spectroscopic study of the effects of gamma-irradiation on RIF-1 tumor cells perfused in vitro. AB - In order to examine the mechanisms underlying radiation-induced changes in phosphorus metabolite levels observed in RIF-1 tumors in vivo, RIF-1 cells in culture were perfused for up to 70 h following gamma-irradiation with 0-25 Gy and monitored continuously by 31P NMR spectroscopy at 8.5 T. Cells immobilized in the sample volume by incorporation into calcium alginate beads were bioenergetically stable, but did not replicate at the cell density used. Following an initial increase in PCr and NTP, which occurred in both control and irradiated cells, a dramatic decline in high-energy phosphates was detected beginning 24-30 h after irradiation with 15 or 25 Gy. In contrast, unirradiated cells or cells treated with 10 Gy remained metabolically stable for up to 72 h. The metabolic changes induced by irradiation of the cultured cells, which reflected cell death and lysis, were distinctly different from those observed in RIF-1 tumors in vivo during the same postirradiation time interval--an increase in high-energy relative to low-energy phosphates. This suggests that the spectral changes in vivo do not result from direct modification of cellular energy metabolism by radiation injury. PMID- 1461115 TI - Automatic in vivo NMR data processing based on an enhancement procedure and linear prediction method. AB - A new data processing method for in vivo NMR data quantitation is presented. This method (EPLPSVD) is based on the enhancement procedure (EP) proposed by J. A. Cadzow (IEEE Trans. Acoust. Speech Signal Process. 36, 49, 1988) followed by the usual linear prediction method using the singular value decomposition (LPSVD). The evaluation of this protocol is performed using synthesized 31P signals with different signal-to-noise ratios. A Monte-Carlo simulation as a function of signal-to-noise ratio (SNR) has proved that EPLPSVD leads to unbiased estimated values of parameters. Then the Cramer-Rao method yields reliable confidence intervals for the estimated parameters. The estimates of NMR parameters using EPLPSVD are reliable and accurate for SNR > or = 1.2 while the LPSVD method failed for SNR < or = 4. This protocol is applied to analyze automatically a series of 31P free induction decays obtained from the human gastrocnemius muscle during exercise. Spectral parameters with their confidence intervals, curves of relative intensity variations in phosphocreatine and inorganic phosphate, and pH curves are automatically provided. PMID- 1461116 TI - Improved cardiac gating and ventilation timing in animal experiments. AB - In this work we present an improved solution for cardiac gating and ventilation timing in in vivo spectroscopic and imaging experiments. This approach makes use of a pulse conditioner to extract primary timing signals from noisy and fluctuating input signals. A timing controller is then used to set all additional timing outputs. Full feedback control is utilized in this timing controller to optimize both magnetic resonance and respiratory timing. Feedback control also helps ensure that timing errors will not occur during acquisition. PMID- 1461117 TI - A piezoelectric respiratory monitor for in vivo NMR. AB - This report describes a simple electronic device employing a piezoelectric element which serves as a sensitive detector of motion. The device is useful as a monitor of respiratory motion for nuclear magnetic resonance animal experiments in vivo. It can also provide a trigger pulse for respiratory gating experiments. PMID- 1461118 TI - Changes in probe sensitivity during NMR spectroscopic studies of the perfused rat heart: a warning. AB - During NMR experiments on isolated, perfused rat heart, we observed a 57% change in probe sensitivity when the perfusion buffer surrounding the heart was replaced by either a low-ionic-strength mannitol solution or air and the heart was made ischemic. Such changes in sensitivity, should they go unrecognized, would result in substantial quantification errors. PMID- 1461119 TI - A simple procedure for obtaining high-quality NMR spectra of semiquantitative value from small tissue specimens: cervical biopsies. AB - The handling of small tissue biopsy samples (< 100 microliters) for NMR investigations poses special problems. Optimal and stable positioning of the samples within the sensitive volume of the radiofrequency coil can be achieved by inserting the sample in a capillary. Methods for quantitation of the spectral information from samples requiring histological evaluation after the NMR experiment are discussed, in particular with respect to cervical biopsies. PMID- 1461120 TI - Real-time observation of transient focal ischemia and hyperemia in cat brain. AB - Gradient-recalled echo-planar (T2*-weighted) imaging was used to noninvasively monitor regional blood oxygenation state changes in real time during transient episodes of focal ischemia in cat brain. Varying ischemic intervals (12 s to 30 min) were caused by middle cerebral artery occlusion. A rapid signal drop was noted upon occlusion, due to deoxygenation of static blood in the ischemic tissues. Upon successful reperfusion, the signal intensity recovered immediately and increased above (overshot) the baseline level before slowly returning to normal. The "overshoot" response was strongly dependent on the duration of the ischemic interval and is thought to reflect reactive hyperemia. PMID- 1461121 TI - Shaping the signal response during the approach to steady state in three dimensional magnetization-prepared rapid gradient-echo imaging using variable flip angles. AB - A theoretical algorithm for shaping the signal response during the approach to steady state in three-dimensional magnetization-prepared rapid gradient-echo (3D MP-RAGE) pulse sequences has been developed and implemented. This algorithm derives the flip angle series required to produce specifically chosen time evolutions of the signal intensities during the data acquisition segment of 3D MP RAGE sequences. Theoretical predictions for the cases of unshaped, uniform, and mono-exponential decay signal responses were quantitatively validated with a doped-water phantom on a 1.5-T whole-body imager and in all cases there was excellent agreement between the theoretical and experimental values. The effects of RF inhomogeneities and eddy currents on the signal response shaping were also investigated. To demonstrate the potential utility of the technique, the signal response shaping algorithm was applied to a T1-weighted 3D MP-RAGE sequence to derive the acquisition flip angle series which theoretically yields the maximum white matter/gray matter signal difference (WGSD) consistent with the chosen response shape. Images obtained from a healthy volunteer using this variable flip angle sequence were compared with 3D RF-spoiled steady-state gradient-echo images obtained in the same total imaging time. The 3D MP-RAGE images demonstrated a 41% increase in the WGSD-to-noise ratio. These initial very promising results indicate that with further refinement to eliminate some intensity artifacts, the variable flip angle 3D MP-RAGE technique may, with respect to certain image properties, provide considerable improvements over currently available 3D gradient-echo imaging techniques. PMID- 1461122 TI - RF current density imaging in homogeneous media. AB - MRI has proven capable of imaging quasistatic volume current densities in electrolytic and biological media. In this paper, the feasibility of extending the method to image RF current density at the Larmor frequency is studied. RF current imaging could be relevant to MR power absorption and safety and to hyperthermia analysis, as well as creating dielectric and conductivity-dependent tissue contrast. The approach is to deliberately induce or inject RF currents in a sample synchronous with an MR pulse sequence and measure the resulting transverse RF magnetic field components. Current density is extracted by computing the curl of the magnetic fields. The preliminary theory has been developed for uniform media where both displacement and conduction currents exist while skin effects or eddy currents are absent. If the derivative in the B0 direction of the RF magnetic field component parallel to B0 is negligible, then sufficient information exists to reconstruct the RF current density component that is parallel to B0 without rotating the sample. The relative phase of the current can also be estimated. The method has been proven feasible by successfully imaging a uniform 85.6-MHz current density in a salt water phantom. The experiment conforms closely to capacitively coupled hyperthermia heating. PMID- 1461123 TI - Fast spiral coronary artery imaging. AB - A flow-independent method for imaging the coronary arteries within a breath-hold on a standard whole-body MR imager was developed. The technique is based on interleaved spiral k-space scanning and forms a cardiac-gated image in 20 heartbeats. The spiral readouts have good flow properties and generate minimal flow artifacts. The oblique slices are positioned so that the arteries are in the plane and so that the chamber blood does not obscure the arteries. Fat suppression by a spectral-spatial pulse improves the visualization of the arteries. PMID- 1461124 TI - A new frontier of blood imaging using susceptibility effect and tailored RF pulses. AB - In MRI, image contrast can be controlled by use of the susceptibility effect if an object contains paramagnetic substances. The localized linear gradient dephases spins in the voxel, leading to phase cancellation and thus reduced signal. This signal void phenomenon, can be exploited if the intrinsic linear gradient is either enhanced or compensated by externally applied RF generated phase distributions. In this paper, a new concept which utilizes the susceptibility effect through the use of tailored RF pulses is proposed. As potential applications of the method, two different types of tailored RF pulses are introduced: one for the enhancement of the susceptibility effect and the other for the correction of the susceptibility artifact, respectively. The former, for example, can be applied to angiography utilizing the paramagnetic property of deoxygenated blood, suggesting a new avenue for the angiography which, for the first time, is not based on flow, although the method is currently limited to imaging of venous blood or venography. Both a theoretical study of the method and experimental results are reported. PMID- 1461126 TI - Projection reconstruction techniques for reduction of motion effects in MRI. AB - Projection reconstruction (PR) techniques are shown to have intrinsic advantages over spin-warp (2DFT) methods with respect to diminished artifacts from respiratory motion. The benefits result from (1) portrayal of artifacts as radial streaks, with the amplitude smallest near the moving elements; (2) streak deployment perpendicular to the direction of motion of moving elements and often residing outside the anatomic boundaries of the subject; (3) inherent signal averaging of low spatial frequencies from oversampling of central k-space data. In addition, respiratory-ordered view angle (ROVA) acquisition is found to diminish residual streaking significantly by reducing interview inconsistencies. Comparisons of 2DFT and PR acquisitions are made with and without ROVA. Reconstructions from magnitude-only projections are found to have increased streaks from motion-induced phase shifts. PMID- 1461125 TI - Sodium ion transport in rat hearts during cold ischemic storage: 23Na and 31P NMR study. AB - The success of heart transplantation is limited by the negative correlation between the length of the cold ischemic storage period and the quality of functional recovery. We use 23Na, 31P NMR spectroscopy, and hemodynamic parameters to describe temperature-dependent changes in sodium influx and the concentration of phosphorus high-energy compounds during different storage periods. Perfusion with Krebs-Henseleit solutions containing Dy(TTHA)3- permitted discrimination of intra- and extracellular sodium during cold ischemic storage. The 23Na NMR visibilities under the acquisition and processing parameters used in our experiments were 40 +/- 4% for the intracellular compartment and 97 +/- 11% for the extracellular compartment. At 4 degrees C, the intracellular Na+ accumulation exceeded that observed at 15 and 22 degrees C. The ATP and PCr depletion rates were much lower at 4 degrees C and the left ventricular contractility was higher after longer periods of storage, as the storage temperature decreased. The intracellular Na+ concentration cannot serve as a marker for the postischemic recovery probability. The relative activity of the Na/K ATPase pumps is not correlated with the preservation success. However, intracellular sodium ion accumulation is a major factor in the time lag of the reperfusion recovery. PMID- 1461127 TI - Phase-scrambled RF excitation for 3D volume-selective multislice NMR imaging. AB - An RF excitation technique with which one can improve the effective dynamic range of the receiver and reduce the interference between slices for 3D volume selective multislice MRI is described. The basic idea of the technique is to use phase scrambling in conjunction with slice encoding through the use of RF pulses. The spins in each slice are encoded by RF pulses which have the scrambled as well as slice-encoded phase components along the slice-selection direction. The scrambled, or randomly distributed, phase reduces the peak signal intensity, thereby reducing the dynamic range of the signal. Since the proposed technique utilizes RF slice encoding together with phase scrambling, interslice image interference is greatly reduced and the dynamic range is improved. In addition, the method has several advantages such as a reduction in the power requirement for the RF pulses and the elimination of the necessity for hardware such as nonlinear gradient coils. PMID- 1461128 TI - 31P transverse relaxation times of the ATP NMR signals of human skeletal muscle in vivo. AB - 31P MRS examinations of the calf muscles of 12 healthy volunteers were performed to determine T2 of the coupled ATP signals by using the 90 degrees-TE/2-2662-TE/2 acq selective spin-echo sequence for elimination of phase and intensity distortions. The T2 relaxation times obtained are much longer than those usually assumed: gamma-ATP, 93 ms; alpha-ATP, 74 ms; beta-ATP, 75 ms. PMID- 1461129 TI - Phosphoarginine-adenosine triphosphate exchange detected in vivo in a microscopic nematode parasite by flow 31P FT-NMR spectroscopy. AB - In vivo flow 31P NMR spectroscopy of a microscopic nematode, Steinernema carpocapsae, is described. Long-term viability was maintained during analysis by continuous circulation of an oxygenated suspension of the parasite through an NMR spectrometer. Saturation transfer and inversion recovery were employed under flowing conditions to investigate the kinetics of phosphoarginine<-->adenosine triphosphate exchange. The kinetic constants for the forward and reverse reactions were 0.37/s and 1.45/s, respectively. This report is the first to demonstrate a functional phosphagen kinase in the metabolism of a parasitic helminth. PMID- 1461130 TI - Cardiac tagging with breath-hold cine MRI. AB - A method is presented for measuring myocardial deformation in a breath-hold with tagged cine MRI. Tagged cine images of human hearts are obtained in arbitrary oblique planes on a standard imager with as few as four heartbeats. The scan time has been reduced 16- to 64-fold from previous techniques. PMID- 1461131 TI - Magnetic resonance neurography. AB - We have made cross-sectional image "neurograms" in which peripheral nerve has a greater signal intensity than that of other tissue. Neurographic images of the rabbit forelimb were obtained using a spin-echo magnetic resonance imaging (MRI) technique that combines fat suppression and diffusion weighting. After fat suppression the nerve shows up in relative isolation and is brighter than the surrounding tissue due to its longer T2 relaxation time of approximately 50 ms compared to approximately 27 ms for muscle. The addition of pulsed gradients for diffusion weighting of the MR signal further enhances the intensity of the nerve signal relative to that of surrounding muscle tissue. The greater diffusional anisotropy of nerve tissue (D parallel/D perpendicular = 3.1) compared to that of muscle (D parallel/D perpendicular = 1.9) allows further enhancement of the nerve by a subtraction of two diffusion-weighted images, one with the gradients oriented parallel and one with the gradients oriented perpendicular to the nerve orientation. We show that by manipulation of the MRI parameters, either echo time or pulsed gradient strength, the nerves can be made to show up as the most intense feature. This verifies the feasibility of generating three-dimensional "neurographic" images, analogous to angiograms, but which demonstrate the peripheral nerve tracts in apparent isolation. PMID- 1461132 TI - Pulmonary arterial brain natriuretic peptide concentration and cardiopulmonary hemodynamics during exercise in patients with essential hypertension. AB - Brain natriuretic peptide (BNP) is secreted through the coronary sinus of the human heart. The purpose of this study was to determine whether BNP secretion from the heart is stimulated by exercise and to examine the relationship between pulmonary arterial BNP concentrations and hemodynamic measurements, especially cardiopulmonary hemodynamics, during exercise in patients with essential hypertension. The exercise protocol consisted of three fixed workloads (25, 50, 75 W) on a bicycle ergometer in the supine position. The mean pulmonary arterial BNP level at rest was 14.8 +/- 4.1 pg/mL, and BNP values gradually increased with higher stages of exercise. At the maximum exercise stage, the BNP value increased to 40.9 +/- 6.5 pg/mL. Close correlations of pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) with pulmonary arterial BNP level were observed at four points at rest and during each stage of exercise. In contrast, heart rate, mean blood pressure, cardiac index (CI), and stroke index (SI) were not correlated with BNP values. Results suggest that cardiac secretion of BNP was increased during exercise in essential hypertensive subjects, and the observed increase of BNP may be related to elevated PAP and PAWP. The enhancement of BNP secretion during exercise in these patients may reflect increased redistribution of blood to the cardiopulmonary compartment. PMID- 1461134 TI - Metabolic availability of oral glucose during exercise: a reassessment. AB - The purpose of this study was to reassess the metabolic availability of oral glucose during prolonged exercise in man, using 13C-labeling and a computation procedure (J Appl Physiol 69:1047-1052, 1990) that correctly takes into account changes in isotopic composition of CO2 arising from oxidation of endogenous substrates (Rendo). These changes are due to glucose ingestion associated with exercise. Each of the seven subjects completed three 2-hour periods of exercise at 67% maximum oxygen consumption (VO2max) on an ergocycle, with ingestion of water (1,000 mL) or 60 g (in 1,000 mL water) of 13C-labeled glucose at two levels of enrichment (13C/12C = 1.11482% and 1.13303%). As expected, Rendo significantly increased from rest to exercise with water ingestion (1.09888% +/- .00196% to 1.09970% +/- .00175%) and with glucose ingestion (1.10002% +/- .00159%) due to changes in the respective contributions of endogenous carbohydrates and fat to energy requirements as assessed by the respiratory exchange ratio (RER). When changes in Rendo were taken into account, the estimated amount of exogenous glucose oxidized was 38.8 +/- 10.3 g. Much higher values were found when Rendo at rest or during exercise with water ingestion were used in the computation (42.3 +/- 10.3 to 65.1 +/- 20.5 g) according to the commonly used method. Examination of data in the literature indicates that the reported oxidation rate of exogenous glucose (g/min) is significantly related to oxygen consumption (VO2) (L/min; r = .592) and that exogenous glucose contributes approximately 14% to 17% to the energy requirement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461133 TI - Effects of different lipid substrates on glucose metabolism in normal postabsorptive humans. AB - We investigated the effects on glucose metabolism of the infusion of either long chain triglycerides (LCT), a mixture of long-chain and medium-chain triglycerides (MCT/LCT), D-beta-hydroxybutyrate (D-beta-OHB), or saline in normal postabsorptive subjects. Plasma insulin, C-peptide, and glucagon concentrations were unchanged in all groups. LCT and MCT/LCT infusions increased levels of plasma free fatty acids (FFA) compared with those of the saline group, whereas D beta-OHB decreased them. Plasma ketone body concentrations were higher during the D-beta-OHB and triglyceride infusions than during the saline test. Glucose concentrations and appearance (Ra) and disappearance (Rd) rates were not modified during saline infusion. Glucose levels decreased only in the D-beta-OHB and MCT/LCT groups (P < .05), whereas they were unchanged during LCT infusion. Glucose Ra decreased slightly by 15% to 17% in LCT, MCT/LCT, and D-beta-OHB groups (P < .05 v saline). Glucose Rd decreased by 14% to 16% in each lipid infusion group (P < .05 v saline). Glucose clearance rates decreased by 14% only in the LCT group (P < .001). Glucose oxidation rates did not change significantly during the lipid substrate infusions compared with saline infusion. In conclusion, (1) the effects of fatty acids on glucose metabolism appear to depend on the fatty acid chain length, since only LCT infusion significantly impaired glucose utilization; and (2) in subjects with normal endocrine pancreas function, we found no adverse effects of a short-term increase in lipid substrate availability on glucose production rate and concentration. PMID- 1461135 TI - The effects of acute elevations in plasma cortisol levels on alanine metabolism in the conscious dog. AB - The present study was undertaken to determine whether an acute physiological increase in plasma cortisol level had significant effects on alanine metabolism and gluconeogenesis within 3 hours in conscious, overnight-fasted dogs. Each experiment consisted of an 80-minute tracer and dye equilibration period, a 40 minute basal period, and a 3-hour experimental period. A primed, continuous infusion of [3-3H]glucose and continuous infusions of [U-14C]alanine and indocyanine green dye were initiated at the start of the equilibration period and continued throughout the experiment. Dogs were studied with (1) a hydrocortisone infusion ([CORT] 3.0 micrograms.kg-1.min-1, n = 5), (2) hydrocortisone infused as in CORT, but with pancreatic hormones clamped using somatostatin and basal intraportal replacement of insulin and glucagon (CLAMP+CORT, n = 5), or (3) saline infusion during a pancreatic clamp (CLAMP, n = 5). Glucose production and gluconeogenesis were determined using tracer and arteriovenous difference techniques. During CLAMP, all parameters were stable except for a modest 67% +/- 6% increase in gluconeogenic conversion of alanine to glucose and a 53% +/- 26% increase in gluconeogenic efficiency. When plasma cortisol levels were increased fourfold during CLAMP+CORT, there was no change in the concentration, production, or clearance of glucose. Gluconeogenic conversion of alanine to glucose increased 10% +/- 34% and gluconeogenic efficiency increased 65% +/- 43%, while net hepatic alanine uptake (NHAU) increased 60% +/- 19% and hepatic fractional extraction of alanine increased 38% +/- 12%. Cortisol did not cause an increase in the arterial glycerol level or net hepatic glycerol uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461136 TI - Beta-cell hypersecretion and not reduced hepatic insulin extraction is the main cause of hyperinsulinemia in obese nondiabetic subjects. AB - Obesity is characterized by peripheral hyperinsulinemia, for which either beta cell hypersecretion, diminished hepatic insulin extraction, or both may be responsible. To clarify this issue, we investigated insulin secretion and hormone hepatic extraction in 18 nondiabetic obese patients (body mass index [BMI], 39 +/ 1.3 kg/m2) and 18 healthy, lean control subjects (BMI, 21.3 +/- 0.7 kg/m2). Body fat distribution was calculated by measuring the waist to hip ratio (WHR). A highly reduced tissue insulin sensitivity (2.4 +/- 0.5 v 9.5 +/- 1.5 10(4).min 1/[microU/mL], P > .0005) and glucose effectiveness, ie, glucose's ability to stimulate its own disappearance at basal insulin (16 +/- 2 v 30 +/- 3 10(3).min 1, P > .005), were found in the overweight subjects compared with the controls. The basal (76 +/- 14 v 37 +/- 4 pmol/L/min) and total (377,848 +/- 5,562 v 16,864 +/- 1,850 pmol/L) prehepatic insulin secretion and the basal (15 +/- 2 v 7 +/- 0.7 pmol/L/min) and total (8,286 +/- 2,009 v 2,840 +/- 210 pmol/L) posthepatic insulin delivery were significantly higher in the overweight subjects compared with the controls (P < .005), whereas the mean hepatic insulin extraction did not differ (77.8% +/- 2.6% v 79.5% +/- 2.6%). A significant inverse correlation was found between the hepatic insulin extraction and the WHR (r = .5, P > .04), signifying the importance of fat distribution in insulin metabolism. The obese patients were subdivided into two subgroups according to their glucose tolerance; eight patients exhibited a normal tolerance and the remaining 10 were intolerant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461137 TI - Polydisperse low-density lipoproteins in hyperalphalipoproteinemic chronic alcohol drinkers in association with marked reduction of cholesteryl ester transfer protein activity. AB - Long-term heavy alcohol intake is well known to increase serum high-density lipoprotein (HDL) cholesterol concentrations. Epidemiologic studies have shown that the protective effect of alcohol intake against coronary heart disease (CHD) is observed in moderate alcohol drinkers, but not in heavy ones. To clarify whether heavy alcohol intake may cause abnormalities in lipoprotein metabolism, we analyzed the plasma lipoproteins in eight male chronic heavy alcohol drinkers with marked hyperalphalipoproteinemia. Although their serum HDL cholesterol levels were remarkably high, ranging from 2.67 to 3.58 mmol/L, three patients had CHD and corneal arcus was present in seven patients. Cholesteryl ester transfer protein (CETP) activity was reduced in all subjects (7.3% +/- 4.2%/10 microL/18 h in alcohol drinkers v 20.5% +/- 2.4%/10 microL/18 h in control; mean +/- SD, P < .001). The CETP mass levels were also markedly reduced in these subjects. The analysis of low-density lipoprotein (LDL) on nondenaturing polyacrylamide gradient gel electrophoresis revealed that four subjects with severely low CETP activity (< 25% of control) had polydisperse LDLs, similar to those observed in genetic CETP deficiency. The other four subjects with approximately half the normal CETP activity had homogeneous but smaller-sized LDLs, as compared with control subjects. Particle size of HDL was larger than that of normal control HDL in all subjects. After cessation of alcohol intake, plasma HDL cholesterol levels were decreased and LDLs became more homogeneous and normal in size, in parallel with elevation of CETP activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461138 TI - Serum cholesterol and lipoprotein concentrations in mothers during and after prolonged exclusive lactation. AB - The effect of exclusive lactation on lipid levels was investigated by evaluating serum concentrations of total and lipoprotein cholesterol, triglyceride (TG), and apoprotein (apo) B in mothers during and after exclusive, prolonged lactation. Serum total cholesterol concentrations were measured at delivery (n = 195), at 2 (n = 165), 6 (n = 119), 9 (n = 74), and 12 months (n = 32) of lactation, and 2 months (n = 27) after ending this exclusive lactation. In a subgroup of 34 mothers, serum levels of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein 2 (HDL2), HDL3, and LDL apo B were determined at 2, 6, 9, and 12 months of lactation. The mean value of serum total cholesterol concentrations decreased from 6.2 +/- 0.12 (SEM; n = 195) at delivery to 4.8 +/- 0.1 mmol/L (n = 116) at 6 months of exclusive lactation (P < .001). The average decrement in total cholesterol level was 0.80 mmol/L (P < .001) from delivery to 2 months of lactation and 0.55 mmol/L (P < .001) from 2 to 6 months of lactation, and levels were stable thereafter. In the 27 mothers who were exclusively breast-feeding their infants at 9 months of lactation and whose serum cholesterol levels were measured 2 months after the end of lactation, cholesterol levels increased rapidly to 5.7 +/- 0.21 mmol/L (P = .001). In the subgroup of 34 mothers who were examined more closely, the course just described was also true for serum TG, LDL and VLDL cholesterol, and LDL apo B levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461139 TI - Influence of dietary composition on energy expenditure during recovery of body weight in the rat: implications for catch-up growth and obesity relapse. AB - The influence of dietary composition on whole-body energetics was examined during the first 2 weeks of isocaloric refeeding after low food intake in a rat model. The high energetic efficiency and energy partitioning toward fat accretion characteristic of this refeeding period were unaltered by (1) dietary fat levels varying between 6% and 30% of energy intake; (2) protein levels between 15% and 40%; (3) carbohydrate types (glucose v fructose v sucrose v starch v unrefined carbohydrate); and (4) diets containing 30% fat but differing in fatty acid composition (long-chain triglycerides [LCT] v medium-chain triglycerides [MCT] v oleic v linoleic v alpha-linolenic metabolites eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] omega-3 fatty acids). Changes were only observed for extreme diets, ie, those deficient in protein or very high in fat. Low-protein diet was the only condition in which the high metabolic efficiency characteristic of the refeeding period was partially suppressed, and this occurred despite a lack of concomitant reduction in body fat deposition. On the contrary, with high fat diets (> 30% of dietary energy consumption) the elevated efficiency was further increased, an effect that was only partially accounted for by the lower energy cost of body fat gain from high-fat diets. These studies indicate that during body weight recovery, the mechanisms underlying the adaptive increase in metabolic efficiency favoring the replenishment of body fat stores override any effect of food type on thermogenesis, and suggest some convergence in the controlling neural pathway. The implications of these findings vis-a-vis nutritional rehabilitation (catch-up growth) and obesity relapse are discussed. PMID- 1461140 TI - Partial enterectomy in the rat does not diminish muscle glutamine production. AB - The hypothesis was posed that consumption of the amino acid glutamine by the splanchnic tissues is an important regulating mechanism for its production in muscle. Therefore, glutamine consumption or production in portal-drained viscera (PDV), liver, and hindquarter was measured by determining fluxes and intracellular concentrations after 80% enterectomy or SHAM operation in rats. Moreover, fluxes and intracellular concentrations of several other amino acids, ammonia, and liver urea production were determined concomitantly. After enterectomy, arterial glutamine concentration was increased, PDV glutamine consumption was decreased by 77%, and liver glutamine consumption was unchanged compared with values in SHAM-operated rats. Although hindquarter glutamine production remained unchanged after enterectomy, intracellular glutamate concentration (glutamine precursor) was lower, suggesting that enterectomy induces changes in muscle metabolism without changing the flux of glutamine. For the remaining gut, it was calculated that after enterectomy glutamine consumption per gram remaining gut tissue increased. These results cast doubt on the hypothesis that diminished splanchnic glutamine uptake can reduce muscle glutamine production. PMID- 1461141 TI - Resting energy metabolism and cardiovascular disease risk in resistance-trained and aerobically trained males. AB - The objectives of this study were (1) to examine differences in resting metabolic rate (RMR) and cardiovascular risk factors among aerobically trained (n = 36), resistance-trained (n = 18), and untrained (n = 42) young males; and (2) to investigate the influence of body composition, dietary intake, and VO2max as possible modulators of differences in cardiovascular risk among groups. Results showed that RMR, adjusted for differences in fat-free weight (FFW), was 5% higher in aerobically trained males compared with resistance-trained males (P < .01), and 10% higher than that in untrained males (P < .01). Plasma levels of cholesterol and low-density lipoprotein cholesterol (LDL-C) were comparable between resistance-trained and aerobically trained males, but were lower (P < .05) than those in untrained males. (The percent intake of dietary fat was related to plasma cholesterol [r = .32, P < .01] and LDL-C [r = .30, P < .01].) When compared with untrained males, fasting triglyceride (TG) levels were 39% and 43% lower (P < .01) in resistance-trained and aerobically trained males, respectively. When compared with untrained males, the fasting insulin to glucose ratio (I/G) was 45% and 53% lower (P < .01) in resistance- and aerobically trained males, respectively. Mean arterial pressure (MAP) was 7% lower (P < .01) in aerobically trained compared with untrained males. Statistical control for differences in percent body fat or percent intake of dietary fat diminished the differences among the groups for plasma lipids, blood pressure, and the I/G ratio. We conclude that aerobically trained and resistance-trained males have higher resting energy requirements independent of FFW compared with untrained males. Aerobically trained and resistance-trained young males have comparable and favorable cardiovascular disease risk profiles compared with untrained males, and this appears to be related to their low level of adiposity and low intake of dietary fat. PMID- 1461142 TI - Postprandial lipoprotein(a) response to a single meal containing either saturated or omega-3 polyunsaturated fatty acids in subjects with hypoalphalipoproteinemia. AB - We have recently reported that the apolipoprotein (apo) B-100-apo(a) complex, the protein moiety of lipoprotein(a) [Lp(a)], has a high affinity for triglyceride(TG)-rich particles (TRP) and that this complex can affiliate with endogenous TG-rich lipoproteins. To shed more light on the apo B-100-apo(a) complex associated with plasma TRP during postprandial lipidemia, we fed five male subjects presenting with primary hypoalphalipoproteinemia (HP) and four male controls a single fat meal (60 g/m2) containing saturated fatty acids (SFA) and, 6 weeks later, an isocaloric meal containing omega-3 polyunsaturated fatty acids. The subjects were phenotyped for plasma Lp(a) and apo C-III levels, apo(a) and apo E isoforms, and lipoprotein lipase and hepatic lipase activities. Vitamin A was included in the meal as a marker of intestinally derived TRP. Following the SFA meal, three of the HP subjects showed a decrease in plasma levels of Lp(a) that lasted 10 to 12 hours in the presence of an increased hypertriglyceridemic response. Two HP subjects who had low preprandial lipoprotein lipase activity and elevated plasma apo C-III levels showed an increase in plasma Lp(a) levels along with the hypertriglyceridemic excursion. However, in all cases, inclusive of the controls, there was an elevation in plasma levels of TRP of Sf greater than 1,000 that contained apo B-100-apo(a) 6 to 8 hours after the meal. This TRP excursion appeared not to be related to the basal levels of plasma Lp(a), high-density lipoprotein (HDL) cholesterol, TGs, or apo(a) and apo E isoforms, and it did not coincide with the retinyl ester peak.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461143 TI - Intrapancreatic islet transplantation in experimental diabetes in the rat. AB - Pancreatic islets have been transplanted successfully to a variety of organs except the pancreas. Since this organ is the most physiologic recipient for islets in rodents with chemically induced diabetes, we have placed neonatal islets intrapancreatically in highly inbred Lewis rats with streptozotocin (ST) diabetes. Transplantation of 2,000 neonatal islets into the pancreas of diabetic rats reversed diabetes within 2 weeks in all of the treated rats (seven of seven). The same success rate was obtained using the same number of islets placed under the kidney capsule in 11 recipients. Although cured of their diabetes, rats in both groups with inadequate islet-cell mass were not able to produce glucose tolerance tests equal to those observed in normal animals. Higher insulin levels were measured in the rats receiving islets under the kidney capsule, as compared with those placed intrapancreatically. In summary, syngeneic islet transplants to the pancreas of ST-diabetic rats are successful in reversing the diabetic state. This model may be useful to the study of islet function after islet transplants into their natural environment. PMID- 1461144 TI - Normal plasminogen activator inhibitor levels at long-term follow-up after jejuno ileal bypass surgery in morbidly obese individuals. AB - Forty-five patients who had been subjected to jejuno-ileal bypass (JIB) surgery for morbid obesity and 10 obese nonsurgery subjects were studied. The former group was examined 14 to 20 years after surgery, and was found to have lower mean plasminogen activator inhibitor type 1 (PAI-1) activity (8.4 v 32 U/mL, P < .001), tissue plasminogen activator (tPA) antigen concentrations (7.2 v 12 micrograms/L, P < .01), body mass index (BMI), and fasting plasma insulin, triglyceride, and cholesterol levels. The PAI-1 levels were correlated with BMI, waist to hip ratio, and insulin, triglyceride, and cholesterol levels. Thus, previously obese subjects have normal PAI levels 14 to 20 years after treatment with JIB surgery, in contrast to the high PAI-1 levels in nonsurgery obese subjects. PMID- 1461145 TI - A high-monounsaturated-fat/low-carbohydrate diet improves peripheral insulin sensitivity in non-insulin-dependent diabetic patients. AB - It is commonly believed that high-carbohydrate (CHO) diets improve peripheral insulin sensitivity; however, this concept is based on anecdotal evidence. Furthermore, it has been demonstrated that in non-insulin-dependent diabetic patients treated with insulin, a high-monounsaturated-fat (MUFA) diet is more effective than a high-complex-CHO diet in reducing blood glucose levels. The aim of our study was to compare the effect of a high-MUFA diet and a high-CHO diet on peripheral insulin sensitivity and metabolic control in non-insulin-dependent diabetic patients. Ten non-insulin-dependent diabetic patients aged 52 +/- 8 years with a body mass index (BMI) of 26.7 +/- 3.5 kg/m2 who were being treated with diet alone (n = 5) or with diet plus glibenclamide (n = 5) were randomly assigned to a 15-day period of either a high-MUFA/low-CHO diet (CHO, 40%; fat, 40%; protein, 20%; fiber, 24g) or a low-MUFA/high-CHO diet (CHO, 60%; fat, 20%; protein, 20%; fiber, 24g) and were then crossed-over to the other diet. Diets were similar in their content of monosaccharides, disaccharides, and saturated fats, and were administered to the patients in a metabolic ward. The dosage of hypoglycemic drugs was maintained at a constant level throughout the study. With the high-MUFA/low-CHO diet, a decrease in both postprandial glucose (8.76 +/- 2.12 v 10.08 +/- 2.76 mmol/L; P < .05) and plasma insulin (195.0 +/- 86.4 v 224.4 +/- 75.6 pmol/L; P < .02) levels was observed. Furthermore, fasting plasma triglyceride levels were reduced after the high-MUFA fat/low-CHO diet (1.16 +/- 0.59 v 1.37 +/- 0.59 mmol/L; P < .01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461146 TI - Correlation between residual beta-cell function and age at onset of spontaneous diabetes in Long Evans Tokushima lean rats. AB - We studied the natural course of disease in spontaneously diabetic rats, Long Evans Tokushima Lean (LETL) rats, to determine whether it showed similar pathogenetic heterogeneity to that of patients with insulin-dependent diabetes mellitus (IDDM) with regard to the relationships between age at onset, rapidity of disease progress, and degree of beta-cell function at the time of its manifestation. Type 1 diabetes developed in 35 rats (6.3%) between 40 and 140 days of age. Eight rats that became diabetic at age 69 days or less were more severely ketotic at the time of first detection of glycosuria and showed more rapid deterioration than seven rats that became diabetic later after birth (mean plasma 3-hydroxybutyrate levels, 4,707 +/- 1,215 pmol/L v 1,390 +/- 859 pmol/L; mean +/- SEM, P < .01). The mean plasma levels and pancreatic content of immunoreactive insulin (IRI) of the early onset rats, 47 +/- 13 pmol/L and 19 +/- 12 pmol/g tissue weight, were significantly lower (P < .01) than the corresponding values of the late-onset rats, 262 +/- 52 pmol/L and 348 +/- 87 pmol/g tissue weight, respectively. Both values were markedly lower than the mean values of 25 nondiabetic LETL rats, 976 +/- 122 pmol/L and 3,488 +/- 628 pmol/g tissue weight. Plasma immunoreactive glucagon (IRG) levels were significantly increased in the diabetic groups (early onset, 57 +/- 13 pmol/L; late-onset, 51 +/- 12 pmol/L; nondiabetic, 18 +/- 1 pmol/L; P < .01). These changes in pancreatic hormone levels of the early onset and late-onset rats were compatible with the histological features of their pancreatic islets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461147 TI - High-density apolipoprotein A-I and A-II kinetics in relation to regional adiposity. AB - High-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations decrease with increasing central adiposity. The present study investigated possible mechanisms for these effects by examining the relationship between body mass index, regional adiposity, and HDL apo A-I and A-II metabolism. Fifteen sedentary men and 10 male endurance athletes aged 22 to 44 served as subjects. HDL apo A-I and A-II metabolism was examined using 125I-labeled autologous HDL. Chest and thigh skinfold thickness and the ratio of chest to thigh skinfold thickness were used as indices of regional adiposity. The relationship of adiposity to HDL metabolism was examined using correlational and multiple regression analysis. In both subject groups, the fractional catabolic rate of apo A-I and A-II increased with increasing chest skinfold thickness and chest to thigh skinfold ratio (.43 < r2 < .66). This effect was partially independent of triglyceride or HDL cholesterol concentrations. Apo A-I and A-II fractional catabolic rates increased with increasing body mass index only in the sedentary men. Concentrations and synthetic rates (mg.d-1.kg-1) of apo A-I and A II were not consistently related to body mass index or regional adiposity. Peripheral adiposity assessed by thigh skinfold thickness was not correlated with any parameter of apo metabolism. We conclude that HDL apo A-I and A-II catabolism increases with increasing central adiposity. PMID- 1461148 TI - Naturally occurring SLE anti-DNA antibodies recognize unique conformation on DNA lysine photoadduct. AB - Native calf thymus DNA has been covalently modified with lysine under UV-A light. Human autoantibodies on purification through affinity column of native DNA linked to polylysyl-Sepharose 4B showed almost equal recognition of DNA and photoadduct. The recognition of DNA-lysine photoadduct by the affinity-purified autoantibodies might be helpful in understanding their origin in SLE vis-a-vis the role of positively charged amino acids in the pathogenesis of autoimmune diseases. PMID- 1461149 TI - Ultrastructural alterations and expression of cytoplasmic antigen 48-1 in hepatocytes in association with hepatitis C virus infection. PMID- 1461150 TI - Temperature-sensitive immunoglobulin A-binding and dimerization of C-terminus impaired protein Arp4 produced in Escherichia coli. AB - A gene for protein Arp4, an IgA receptor protein derived from Streptococcus pyogenes AP4, was expressed in Escherichia coli. The product was demonstrated to be accumulated in a periplasmic space as a polypeptide with an apparent molecular weight of 40 kDa with the deleted C-terminal membrane anchor portion of protein Arp4. This 40-kDa peptide of the C-terminus-impaired recombinant protein Arp4 produced in E. coli, designated ir-protein Arp4, was purified from a periplasmic fraction of transformants and its IgA-binding activity was analyzed. The IgA binding of ir-protein Arp4 was temperature-sensitive, that is, ir-protein Arp4 bound IgA at 4 and 25 C, but did not at 37 C. In addition, the dimerization of ir protein Arp4 was also temperature-sensitive in parallel with temperature dependent binding activity, suggesting that the dimerization of ir-protein Arp4 may be required for its active binding to IgA. In contrast, ir-protein Arp4 immobilized on Sepharose 4B did bind to IgA even at 37 C as well as 4 and 25 C. The immobilized ir-protein Arp4 might acquire the temperature-resistant IgA binding activity in part through the formation of a stable dimerized ir-protein Arp4 on the solid support. PMID- 1461151 TI - Involvement of calcium in germination of coat-modified spores of Bacillus cereus T. AB - The effect of calcium on germination of coat-modified Bacillus cereus T spores was investigated. Coat-modified spores produced either by chemical extraction (SDS-DTT-treated spores) or by mutagenesis (10LD mutant spores) were unable to germinate in response to inosine. While SDS-DTT-treated spores could germinate slowly in the presence of L-alanine, 10LD mutant spores could not germinate at all. The lost or reduced germinability of coat-modified spores was restored when exogenous Ca2+ was supplemented to the germination media. The calcium requirement of coat-modified spores for germination was fairly specific. The simultaneous presence of germinant with Ca2+ was also required for germination of coat modified spores. The optimal recovery of germinability was observed in the presence of 1.0 mM of calcium acetate. The calcium requirement itself was remarkably diminished under the condition in which L-alanine and a certain purine nucleoside analog, adenosine or inosine, coexisted. The lost or diminished germinability observed in SDS-DTT-treated spores or 10LD mutant spores may be attributed to the loss of calcium associated with the spore integuments. PMID- 1461152 TI - Phage pattern and antibiotic resistance pattern of coagulase-negative staphylococci obtained from immunocompromised patients. AB - A total of 152 coagulase-negative staphylococcal strains were isolated from clinical samples of 14 patients hospitalized after bone-marrow transplantation in a specialized hospital ward in Hungary, during an 18-month period between 1987 and 1989. Two species, Staphylococcus epidermidis and Staphylococcus haemolyticus, predominated (each, 45%). Using Pulverer and co-workers' phage set for typing, 68% of the isolates were typable; 16 phage patterns were observed. A characteristic long pattern with phages Ph10/Ph13/Ph15/U4/U15/U16/U20/U33 /U46 appeared only in S. epidermidis, among 5 of 11 colonized patients (8.5% of all strains). Single lysis with phage Ph13 was observed in 7 of the 14 patients (49% of all strains), in species S. capitis, S. epidermidis, S. haemolyticus, S. hominis, and S. warneri. In S. haemolyticus, non-typable strains predominated (66%); this character occurred only in 2% among other species. The strains colonizing the immunocompromised patients differed from each other in phage pattern, antibiotic resistance pattern, and/or slime production. No hospital infection was suggested. On the other hand, high incidence of two well-definable phage patterns raises some relationship between phage receptors or some regulatory systems in phage multiplication and factors responsible for special colonization as common surface properties. PMID- 1461153 TI - Structural studies of peptidoglycans in Campylobacter species. AB - Peptidoglycans (PG) from Campylobacter coli, Campylobacter jejuni, and Campylobacter fetus were composed of muramic acid, glucosamine, alanine, glutamic acid, and diaminopimelic acid in a molar ratio of 1.1:1:1.7:1.1:09. Thirty percent of the amino groups of diaminopimelic acid were involved in cross linkages between peptides. During cultivation, C. coli and C. jejuni changed from a spiral to a coccoid form. In C. coli, we could isolate PG only from the spiral forms in yields of 0.8-1.2% by dry weight. C. fetus did not change to a coccoid form, and always contained PG. Thus, it is possible that the morphological transformation from the spirals to the coccoid forms of C. coli and C. jejuni is accompanied by, and probably due to, the degradation of PG. PMID- 1461154 TI - Characterization of the dextranase purified from Streptococcus mutans Ingbritt. AB - We purified dextranase from the culture supernatant of Streptococcus mutans Ingbritt by procedures including ammonium sulfate precipitation, ion-exchange chromatography, and gel filtration. The molecular weight of the enzyme was estimated as 78 kDa by SDS-PAGE. The enzyme degraded dextran at the optimum pH of 5.5, but not other glucans and fructans at all. Paper chromatographic analysis revealed that the enzyme cleaved dextran by an endo-type mechanism. The enzyme was inhibited by Hg2+, Fe3+, Zn2+, and anionic detergents SDS and deoxycholic acid, but not inhibited by non-ionic detergents Triton X-100, Lubrol PX, Nonidet P-40, and Tween 80. SDS-blue dextran-PAGE analysis of the culture supernatant revealed that the enzyme activity detected in the 96 kDa band shifted gradually to the 78 kDa band during handling the supernatant. This shift was inhibited by phenylmethylsulfonyl fluoride, suggesting that the shift of the molecular size is due to proteolytic degradation of the enzyme by serine protease. PMID- 1461155 TI - IgG subclass alterations in adult asthma. AB - Immunoglobulin levels were measured in serum samples of 12 black adult non smoking asthmatic patients, 11 females and 1 male, and compared with 15 age-, sex matched normal controls. Their total IgG, IgA and IgM levels were within the normal range. However, on quantitation of subclasses, IgG1 levels were significantly above normal, while IgG2 and IgG3 levels were significantly lower than those of controls. No significant differences were found between the two groups when IgG4 levels were compared. These studies as well as those of others suggest that immunoglobulin administration, particularly of individual subclasses, might prove to be a beneficial addition in the management of this condition. PMID- 1461157 TI - Interprofessional education. PMID- 1461156 TI - The protective activity of tea catechins against experimental infection by Vibrio cholerae O1. AB - Tea catechins inhibited the fluid accumulation induced by cholera toxin in sealed adult mice. The catechins also reduced fluid accumulation by Vibrio cholerae O1 in ligated intestinal loops of rabbits. These findings suggest that tea catechins may possess protective activity against V. cholerae O1. PMID- 1461158 TI - Humanitas in medical education. PMID- 1461159 TI - Should medical students be selected only from recent school-leavers who have studied science? AB - This study was undertaken to investigate the apparently widespread belief that in order to be successful at medical school, aspiring candidates must have a sound academic background based predominantly on the study of the natural sciences, be school-leavers aged about 18 (in the non-college educational environments such as Australia or the United Kingdom) and preferably be men. The demographic background and prior academic achievement of individual students entering the University of Newcastle Medical School between 1978 and 1989 has been reviewed and compared with their progress in medical studies. The data show that in the Newcastle medical school environment there is no significant correlation between outcome and previous study of any of the natural sciences. However, significant correlations between outcome and performance in the humanities in general, and English in particular, were found. In this regard a weak background in these subjects correlated with an increased tendency not to complete the medical course. There were no significant correlations found between outcome and age at entry, sex or levels of prior academic achievement (within the top 10% achievement band studied). In summary, the study offers no support for the current selection criteria dominating medical school admissions processes. PMID- 1461160 TI - A comparison of the interviewing skills of first- and final-year medical students. AB - This study compared the communication skills of randomly chosen first- and final year medical students. The intention was to follow up previous research, conducted over 10 years ago, into the effects of the medical curriculum on communication skills. It was hypothesized that there would be little improvement in such skills over the period of training, with the possibility that the final year students might be less caring, empathic and supportive, more directive, and less concerned with psychosocial information. All students interviewed a simulated patient in the role of a mother of a child with cerebral palsy, where the main problems were psychological and social. The interviews were recorded on videotape and analysed by an independent observer for the presence or absence of a set of communication behaviours considered important in facilitating an effective relationship and in the exploration and understanding of the problem. The results failed to support the hypotheses. The final-year students were superior to their juniors on several measures, indicating improvements in relating to the patient in a caring, empathic, facilitative and listening manner. They also elicited more information relevant to the problem. The indications were that these final-year students were more skilled than in earlier studies, suggesting that the general change in attitudes to communications skills and the limited, but increased input into the curriculum may be having effect, even though there remains a need for considerably more training. PMID- 1461161 TI - A skills programme for preclinical medical students. AB - An education programme in which preclinical medical students are introduced to common procedural skills is described. This programme is presented by a multidisciplinary health care team using short lectures, demonstrations, mannequin practice, and, in selected instances, practice on class-mate volunteers. The programme was evaluated by the students immediately following the presentation and for one class during their clinical activities one year later. The students' support for this programme was generally enthusiastic and remained undiminished upon reflection 12 months later. PMID- 1461162 TI - Learning, retention and recall of clinical information. AB - A representative group of 33 medical students who were entering the junior year clerkships was tested for retention and recall of clinical information 3 months after taking an examination on the same subject. The students were not given an opportunity to review the subject. On 39 identical multiple choice test questions, the students' mean score declined 10 percentile points (P < 0.05) from that on the original examination. On 40 comparable but previously unseen questions, the mean score fell 19 percentile points from that attained 3 months earlier. On open-ended questions of clinical reasoning, a third component of the assessment, the students performed at a level similar to those on the two multiple choice tests, but with greater variability. These assessments give data on retention and recall that have not previously been reported in the literature. Correlations among individual test components were moderate (r = 0.52-0.63). There was inconsistency of individual students in scores on the component tests, and, thus, variability in performance by students was marked. Retention and recall were weakly predicted by results on an initial multiple choice examination. In addition, on a subsequent assessment of knowledge, results from different types of tests were inconsistent, suggesting that these tests evaluate different forms of competence. PMID- 1461163 TI - Students' written reports as an essential part of a case-based learning programme in anatomy. AB - This paper reports on second-year medical students' views and performance on the written reports for the cases that were studied in a case-based learning programme in anatomy at the University of Otago in 1988. The mean marks for the reports for the three main categories of student entry are presented. Differential performance on the written reports relative to the case-based component of the examination held at the end of the year has been determined for each student in the class and ranked in order. The proportions of students falling in the top and bottom quartiles for the class are given. The data taken together indicate that with an intensive programme of case-based learning in 1988, optimal performance in the written reports was reached at an early stage by the graduates whereas the two undergraduate categories improved their performance towards the end of the programme. PMID- 1461164 TI - Active and problem-based learning: two years' experience in physiology at the Medical School of the University of Barcelona. AB - Traditional educational methods are used in most medical schools. The introduction of new methods including active and problem-solving learning in traditional medical schools is difficult. The aims of this experiment were: (1) to introduce a self-learning system with a problem-solving approach in physiology; (2) to promote active student participation; (3) to introduce early clinical exposure; (4) to evaluate the response of the students to this experiment; and (5) to evaluate the feasibility and usefulness of a self-learning and problem-solving approach in only one discipline. Our experience has shown that it is possible to change the learning system in a traditional medical school, with good acceptance by the students and with a high level of satisfaction on the part of the teachers. PMID- 1461165 TI - Education in family and community health: the challenge faced by a new medical school. AB - This paper describes the efforts of the Department of Family and Community Health at Sultan Qaboos University in providing opportunities for the development of 'hands-on' problem-solving skills appropriate for Oman. The curriculum of the Department is discussed, highlighting the unusual emphasis of this discipline in both the preclinical and clinical curriculum of the College of Medicine. The importance of continuous assessment and supervision of students is discussed. Course-work in the preclinical curriculum of the Department is kept to a minimum. Field-work forms an important part of preclinical training, where application and problem-based learning are emphasized. During the clinical years the students are exposed to an integrated series of lectures and practicals covering core knowledge in clinical medicine. Practical clinical training, over a total period of 15 weeks, takes place at a variety of sites where common problems in primary health care in Oman are handled by students under supervision. PMID- 1461166 TI - The development and evaluation of Basic Epidemiology: Student's Text. AB - This paper describes the development and evaluation of a World Health Organization book Basic Epidemiology: Student's Text. This book was a response to a need identified by members of the WHO Global Environmental Epidemiology network. A draft was commented on by members of the Network and then at an editorial meeting. Two thousand copies of a pre-publication version were prepared and this version was formally evaluated by 13 teachers of introductory courses of epidemiology and less formally by members of the Epidemiology Network. A high response was received to the evaluation questionnaires; 45% of the students rated the test overall as 'very useful' and another 54% as 'useful'; many useful comments were received and were incorporated into the final version which will be published by WHO in 1993. PMID- 1461167 TI - The contribution of general practice to medical education: expectations and fulfillment. AB - The aim of this study was to discover what students expected to learn during their fourth-year general practice attachment, to compare this with their GP tutors' expectations and to determine the extent to which the students' expectations were fulfilled. Questionnaires were used to gather this information; students completed them on the first and last days of the 4-week attachment and tutors shortly after the attachment. Students and their tutors had the highest expectations of the course in helping to raise awareness of the psychological and social aspects of ill health and develop clinical decision-making and management skills. At the end of the course students thought that they had gained most in these areas. Both students and tutors had lower expectations of the course helping to develop physical examination and practical skills and to improve knowledge in certain clinical areas. These were also rated lowest in terms of fulfillment. This study was carried out at a time when it is being suggested that more undergraduate teaching should take place in general practice and that this could include the teaching of practical skills and clinical subjects traditionally associated with hospital-based teaching. The results suggest that the expectations of students and GP tutors would need to be modified, as well as extra resources provided, if there is to be a shift in teaching towards the community. PMID- 1461168 TI - Independent learning among general practice trainees: an initial survey. AB - Self-directed learning is a natural way for adults to learn. Vocational training for general practice is a preparation for unsupervised clinical work that will be supported, in the main, by continuing medical education. This study uses the Self Directed Learning Readiness Scale to investigate factors influencing readiness for such learning among a sample of general practice trainees. Three principal factors emerged from analysis: enjoyment and enthusiasm for learning; a positive self-concept as a learner and a factor suggesting the possibility of a 'reproducing' orientation to learning. These factors may reflect approaches to learning in general rather than these adopted for professional learning, but offer helpful pointers for the development of both vocational training and of continuing medical education. PMID- 1461169 TI - Assessing clinical competence at the undergraduate level. AB - This booklet aims to provide relevant background information and guidelines for medical school teachers in clinical departments charged with assessing the clinical competence of undergraduate students. It starts by emphasizing the difference between clinical competence and clinical performance. An approach to defining what should be assessed is outlined. The technical considerations of validity, reliability and practicability are discussed with reference to the ward or practice-based setting and to the examination setting. The various methods available to assess aspects of competence are described and their strengths and weaknesses reviewed. The paper concludes with a discussion of the important issues of scoring and standard setting. The conclusion is reached that the quality of many current assessments could be improved. To do so will require a multi-format approach using both the practice and examination settings. Some of the traditional methods will have to be abandoned or modified and new methods introduced. PMID- 1461170 TI - A factor in the increased risk of colorectal cancer due to ingestion of animal fat is inhibition of colon epithelial cell glutathione S-transferase, an enzyme that detoxifies mutagens. AB - Dietary animal fat increases the risk of colorectal cancer. A factor in the increased risk is hypothesised to result from the inhibition of isoforms of a colonic epithelial cell enzyme that detoxifies genotoxins, glutathione S transferase, by one of the major secondary bile acids produced in the colon by fat digestion, lithocholic acid. The inhibition allows mutagens to persist in colonic epithelial cells while proliferation is stimulated by secondary bile acids, with a concomitant greater frequency of neoplasia-associated mutations than when proliferation is stimulated in the absence of the mutagens. Elements in the hypothesis include the ability of relatively low concentrations of lithocholic acid to inhibit isoforms of glutathione S-transferase found in colon epithelial cells, entry of lithocholic acid into the epithelial cells, and the correlation of neoplasia-associated colon pathology with high levels of lithocholic acid in fecal water. Higher pH values in the colonic stream are identified as exacerbating the effects of lithocholic acid by increasing its solubility. Lithocholic acid is suggested to be more inhibitory to glutathione S transferase than the other major colonic secondary bile acid, deoxycholic acid, on the basis of inhibition-structure relationships. PMID- 1461171 TI - Could diet be one of the causal factors of Alzheimer's disease? AB - Recent developments show that the brains of persons who have died from Alzheimer's Disease (AD) have a deficiency of Essential Fatty acids in one of the principal classes of phospholipids. It is hypothesized that faulty brain cell membranes resulting from this deficiency may allow passage of an enzyme into the bilayer membrane space which cuts beta amyloid precursor proteins attached to such cells at a critical intramembrane position releasing a complete sequence of beta amyloid protein into the extracellular space. Beta amyloid protein appears to be the principal active constituent of senile plaques thought to be a probable cause of brain damage resulting in AD. Treatment of persons suffering from AD with desferrioxamine, a trivalent ion chelator to remove aluminium has shown results in slowing the progression of this disease, implicating aluminium and/or other chelated substances in its etiology. Both EFA deficiency and aluminium build-up may be prevented by dietary precautions. PMID- 1461172 TI - Sudden infant death syndrome (SIDS) and the immune response. AB - Vitamin E pretreatment significantly prevented E. coli-induced Disseminated Intravascular Coagulation (DIC) in rats (1). DIC, a reduction in fibrinogen and a falling platelet count and diffuse haemorrhage are part of the clinical features of Haemorrhagic Shock Encephalopathy Syndrome (HSES), recognised as a disease entity in the 1980s (2). At the SIDS Conference 1974 Reisinger described the effect of Escherichia coli (E. coli) endotoxin on the rabbit (3). An early effect was a reduction in fibrinogen and a falling platelet count, resulting in the release of relatively large amounts of the neuro-transmitter serotonin, stored in platelets (3, 4). Fibrinogen inhibited the release of serotonin from platelets (24). Serotonin is released from platelets during platelet aggregation (14). Platelet aggregation is inhibited by vitamin E (1). Serotonin is a neuro transmitter associated with deep sleep, respiratory movements and cardiovascular collapse (3). Death at a later stage involved vascular permeability, edema and haemorrhage. After fibrin-platelet clots had formed DIC was present in lungs, kidneys and other organs (3). Medical researchers in Australia linked almost half of SIDS victims with a poisonous strain of intestinal E. coli bacteria (5). Dietary selenium in the intestinal villous tip is considered a daily modulator of cytochrome P450-dependent metabolism of drugs and toxins absorbed by intestinal mucosa (6). Villous atrophy occurs in HSES (2). PMID- 1461173 TI - Hypotensive drugs and the cellular energetic potential. AB - Clinical and experimental investigations have revealed changes of the Na, K, Ca and Mg concentration in serum and cells in patients with essential arterial hypertension (EAH). Some hypotensive drugs correct, more or less, the electrolytic abnormalities at the same time as the decrease of arterial pressure. Epidemiological studies have shown a lower arterial blood pressure in populations with decreased intake of Na and an increased intake of K, Ca and Mg. However the most frequently encountered electrolyte anomaly in patients with EAH is hypophosphatemia, mainly induced by a shift of inorganic phosphate from serum into the cells. Probably the increased influx of inorganic phosphate from the serum, increases the arterial cellular energetic potential. As hypotensive drugs lead to a reduction of the inorganic phosphate shift from serum into the cells one may suggest that the obtained decrease of arterial blood pressure may be at least partially due to a diminished energetic potential of certain cells. PMID- 1461174 TI - Understanding the role of oxyradicals in general and in toxic hepatic damage can help safer drug design. AB - The existence and importance of free radicals are well established both theoretically and in in vivo experiments. Methods and techniques are now available to demonstrate the formation of free radical metabolites of natural substances and xenobiotics. Theories of the biological effects of free radicals could be unified and used for a better understanding of the complex processes of the organism. Pharmacology can gain profit from this multidisciplinary approach, which helps to design safer drugs. The theories of free radicals and the results of experiments with antioxidants could help to decrease the oxidative stress caused by pharmaceutical chemicals. PMID- 1461175 TI - Hormonal therapy for stomach cancer. AB - Stomach cancer is one of the major cancers in Asia. Recent advances in diagnosis and surgical techniques have improved the survival of patients with gastric cancer. But radiation and chemotherapy had limited value in promoting the outcome of patients with gastric cancer. Hormonal therapy with tamoxifen had been tried with conflicting results. Previously, we have found that estrogen receptors (ER) were present in 50% cases of Chinese patients with gastric cancers. Recently, the amplification of c-erbB-2 oncogene and its overexpression have been found to correlate with the advancement of lung, ovarian, breast and gastric cancers. In addition, estrogen has been found to inhibit the expression of c-erbB-2 through ER in breast cancer cell lines. A hypothesis is that the same event may occur in ER-positive gastric cancer cell. Thus patients with gastric cancers whose tumors were positive for both ER and c-erbB-2 gene expression, may benefit from estrogen therapy rather than tamoxifen therapy. PMID- 1461176 TI - Nitric oxide-mediated neuronal injury in multiple sclerosis. AB - Although several explanations have been proposed for destruction of myelin and oligodendrocytes in multiple sclerosis, there is no proven mechanism of injury. We postulate that the autoimmune response seen in multiple sclerosis results in a cytokine-mediated increase in nitric oxide production by macrophages/microglia, smooth muscle cells and/or endothelium of the central nervous system. 3 mechanisms of cellular damage due to nitric oxide are proposed: 1. direct nitric oxide cytotoxicity; 2. injury due to peroxynitrite formation from superoxide anion and nitric oxide; and 3. nitric oxide-mediated elevations of cellular cGMP that enhance tumor necrosis factor-alpha toxicity. In support of these hypotheses, the anti-inflammatory effectors, dexamethasone and transforming growth factor-beta, ameliorate symptoms seen in clinical multiple sclerosis and experimental allergic encephalitis, respectively. These 2 immunomodulators also inhibit induction of cytokine-mediated nitric oxide production by macrophages. An experimental design and therapeutic interventions which will evaluate the role of nitric oxide in the pathophysiology of experimental allergic encephalitis are presented. PMID- 1461177 TI - The role of lipid peroxidation in McArdle's disease: applications for treatment of other myopathies. AB - Experimental therapies for McArdle's disease have been directed toward increasing substrate availability to exercising muscle. Such therapies to date have proven largely unsuccessful. These include administration of isoproterenol to increase blood flow, glucagon treatment to elevate serum glucose and increased dietary fat intake. Each of these therapies also results in greater levels of unesterified fatty acids in blood. More recently, a high protein diet is suggested to provide increased amounts of amino acids which would be available as fuel sources. We hypothesize that the absence of myophosphorylase in McArdle's disease creates an imbalance between the enzymes of the redox systems that control the generation, propagation and inactivation of free radicals. This occurs because muscle cells are forced to rely more heavily on fatty acid oxidation. The resulting free radical damage to cellular components disrupts metabolic control and increases the permeability of membranes. Elevated levels of Ca2+ in the sarcoplasm activate proteases, phospholipases and other catabolic enzymes initiating muscle fatigue and cramping. Lipid peroxidation is a consequence of normal muscle activity and may occur unchecked in individuals with McArdle's disease. Continued muscle activity in the absence of a favorable nutritional environment may promote the progression of the disease by increasing susceptibility to oxidative stress. PMID- 1461178 TI - Bioregulatory roles for fibrin(ogen) on blood coagulation. AB - A high plasma fibrin(ogen) concentration is a known risk for thrombosis and cardiovascular disease. Because fibrin(ogen) binds alpha-thrombin with high affinity, it has potential to modulate the interactions of the enzyme with its inhibitors and other substrates in plasma. In particular, fibrin moderates the inhibition of thrombin by antithrombin III and antithrombin III/heparin. Recently, we have demonstrated a novel regulatory role for fibrin(ogen) on plasma coagulation. A push-pull hypothesis is proposed for bioregulation of coagulation by fibrin(ogen). The experimental work which led to the formulation of this hypothesis is outlined. PMID- 1461179 TI - Turner syndrome as a candidate pseudoautosomal disorder. AB - Turner syndrome has been clearly associated with the absence of an X chromosome, but it remains uncertain how this deletion produces either the range of defects regularly associated with the syndrome or those only occasionally seen. It is of particular interest in this regard that the pseudoautosomal portion of the X chromosome has recently been identified as the location for the GM-CSF receptor gene. It is submitted that Turner syndrome, with its hemizygosity for the psuedoautosome, may be an important model for studying the GM-CSF receptor gene as well as other associated genetic material. PMID- 1461180 TI - Clues to prolific productivity among prominent scientists. AB - In a survey based on the biographical sketches, obituary notes and eulogies of notable scientists, eight were identified as belonging to an elite group, having authored more than 1000 research publications, which include books, monographs and patents. They were, in chronological order, Thomas Alva Edison, Paul Karrer, Margaret Mead, Giulio Natta, Hans Selye, Herbert C Brown, Tetsuji Kametani and Carl Djerassi. Among these, Karrer, Natta and Brown were Nobelists in chemistry. Four criteria which can be identified as clues to their prolific productivity are, 1) enthusiasm for compulsive work and eccentric life style, 2) physical and/or environmental handicap, 3) pioneering efforts in a new research field, and 4) selection of research area, predominantly organic chemistry. PMID- 1461181 TI - Infant colic: the effect of serotonin and melatonin circadian rhythms on the intestinal smooth muscle. AB - It is hypothesized that in the evening, peak serotonin concentration causes intestinal cramps associated with colic because serotonin increases intestinal smooth muscle contractions. Melatonin has the opposite effect of relaxing intestinal smooth muscles. Both serotonin and melatonin exhibit a circadian rhythm with peak concentrations in the evening. However, serotonin intestinal contractions are unopposed by melatonin during the first 3 months because only serotonin circadian rhythms are present at birth. Melatonin circadian rhythms appear at 3 months of age. The cramps of colic disappear at 3 months of age. PMID- 1461182 TI - The cytokine theory of headache. AB - Immune cell cytokines are proposed as the common mediators of headache. This unifying concept can not only account for headache, but also the prostaglandins, leukotrienes, platelet activating and vasoactive substances linked with headache, the varied symptoms associated with headache and the high incidence of headache with depression, infectious disease, trauma and in premenopausal women. The immune system as the central mediator of headache is consistent with the promoting effect of estrogen, the abortive activity of cortisol and the prophylactic properties of fish oil and evening primrose oil. This hypothesis provides a unified mechanism to explain headache triggered by food, infectious disease or trauma. PMID- 1461183 TI - An overview of the effects of convergent magnetic ionizing radiation on biological function. AB - This paper provides new theoretical premises for understanding issues in 'bio electromagnetics'. It firstly explains how converging magnetic fields, e.g. dipoles, can exert pressure on electrolyte distribution in an aqueous medium, and then it expands on this point to explain how this magnetic pressure is, in one extreme, a potential cancer causing force in the environment, and is, in another sense, a powerful new technique in cancer treatment. Included in this examination is a short analysis of the importance of this force in the morphogenesis of the fetus, and in the control of chromatic expression after the fact. PMID- 1461184 TI - Models of cell population in tumours and possibility of their application to optimization of radiotherapy. AB - Two models of cell population in tumours are analyzed and used to explain some experiments on the influence of radiation on tumours. There is a proposal to remove disagreements between these models and experiments by the assumption that cells under the influence of a destructive factor may reduce their degree of differentiation. PMID- 1461185 TI - Fatigue syndromes: new thoughts and reinterpretation of previous data. AB - Recently, the author has identified 19 patients who have complained of marked fatigue that had abnormal responses to copper test bracelets or necklaces. At this time, 8 have been shown to have at least one enzyme deficiency in the heme pathway. These patients have been diagnosed with multiple sclerosis, chronic fatigue syndrome and other non-specific diagnoses. A lengthy but still limited review of the literature was performed regarding the following conditions: multiple sclerosis (MS), hepatic porphyria (HP), chronic fatigue syndrome (CFS) and paralytic polio (PP). The text will focus on similar epidemiologies, laboratory findings and clinical courses. Copper as a common but not unique etiologic agent will be discussed; as will the heme pathway, a biologic process that may be disordered in all. PMID- 1461186 TI - Precipitous stem cell (SC) differentiation and 1/f noise. AB - After a brief digression on certain types of noise of generic interest, it is concluded that 1/f noise offers interesting interpretations for unusual modes of SC differentiation such as the precipitous maturation of a subset of the macrophage lineage. Functionally equivalent to weak, spurious sources these specialized cells support the proliferation and maturation of erythroid cells extending thus the stimulatory influence of true, strong sources although in a rather indirect fashion. PMID- 1461187 TI - Estimating left ventricular work by gated blood pool ventriculogram. AB - Utilizing simplifying assumptions and a formula for ventricular radioactivity versus time, a method is presented for the estimation of systolic ventricular work. This value in MKS units is calculated from data available from the radionuclide blood pool ventriculogram. PMID- 1461188 TI - [Use of statistics in occupational medicine. Analysis of papers presented at the national congresses of the Italian Society of Occupational Medicine and Industrial Hygiene]. AB - The statistical methods used in occupational health studies were evaluated by analyzing the papers published from 1986 to 1990 in the proceedings of the annual meetings of the Italian Society of Occupational Medicine and Industrial Hygiene, in order to calculate the degree of understanding of the readers provided with only one-sided knowledge of statistical subjects and to improve the educational objectives in postgraduate schools of occupational health. Almost 70% of the 1151 articles reviewed contained some kind of statistical analysis: methods more complicated than descriptive statistics were used in about 35%. Student's t test (15%) and chi square (12%) were the most common methods. Other methods were less frequently used, so that it was possible to estimate that the learning of any new method would improve the understanding of about 1-2% of the articles. A wider use of statistical methods in data analysis is recommended; the attainment of a higher level of statistical knowledge should be a priority target in occupational health training. PMID- 1461189 TI - [Alcohol consumption by refuse collection workers: a problem of public health]. AB - A total of 485 workers were interviewed employed by the municipal urban refuse collection corporation of Venice; 87.6% consumed alcoholic beverages, 24.5% of whom exceeded 1 litre of wine per day. Only 9.7% of the interviewees thought that an acceptable alcohol consumption level should not exceed 1 litre, whereas more than 23% thought that 2 or more litres of wine per day was not harmful. The variables associated with a high alcohol consumption in this working community were mainly: level of education and of specific knowledge about alcohol and long term residence in the historical centre of Venice. The authors discuss the possible factors connected with the type of job which could influence the incentive to drink and the public hygiene actions that could be taken. The need for community medicine programmes is emphasized. PMID- 1461190 TI - Five cases of pleural mesothelioma with endemic pleural calcifications in a rural area in Greece. AB - The authors describe 5 cases of pleural mesothelioma in a rural population of Macedonia, Greece. This population had been covered by an X-ray study over a 3 year period to detect pleural calcifications compatible with asbestos exposure. The study revealed a 24.2% prevalence of pleural plaques among the inhabitants aged over 40 years of 7 rural villages. High contents of asbestos (chrysotile and tremolite)--up to 90% by volume--were found in the material that was used for whitewashing the houses up to 1935. Even now, environmental concentrations of 0.01 fibres/ml were recorded in the houses. The prevalence of pleural mesothelioma in this rural population is high compared to the general population. A possible explanation of the phenomenon may be a cumulative environmental exposure to asbestos which, even though presumably within the acceptable limits for occupational exposure, lasted over a much longer time period, in terms of both daily exposure and total duration. PMID- 1461192 TI - Cadmium exposure and Wegener's granulomatosis: case report. PMID- 1461191 TI - [Ocular hypertension in radiologists and radiology technicians]. AB - Ionizing radiations (IR) produce changes in the eye and, above all, in the lens. Several studies on radiotherapy in neoplastic diseases and dangerous nuclear accidents like Chernobyl have indicated the percentage and the exposure level at which the eye becomes the target organ of IR. The aim of the study was to establish the association between ocular tension and low-level IR exposure. The incidence of ocular hypertension in the general population is about 1-2% in persons aged 30-40 years and 10% in the 70-80 years age group; the frequency of glaucoma is 0.2-0.5% in persons aged 50-55 years and 2% in those aged 70 years and over; after 15 years of disease, conversion from ocular hypertension to glaucoma is observed in 40% of the cases. We examined 128 subjects occupationally exposed to IR (42 radiologists and 86 radiology technicians) and 130 non-exposed. For each subject we recorded age, length of employment, job titles, dosimetry, ocular tension, refraction and motility impairments. The data obtained from a complete ophthalmologic test was analyzed by the t-Student test, Chi-square and Pearson's test. The ocular tension of 33 occupationally exposed subjects and 2 non-occupationally exposed subjects was higher than the cut-off value of 18 mmHg. There was no analogy between age distribution of ocular hypertension in the groups under study and the general population. There seems to have been a relationship between ocular tension and job titles since a higher incidence was observed among the radiology technicians than among the radiologists and also in the 30-40 years age class.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461193 TI - [Postural tenosynovitis caused by misuse of a computer input device (mouse)]. AB - Several reports of postural problems among video display unit workers are available, most frequently involving the back, neck and shoulder. The case described is an example of tenosynovitis of the right wrist at the point where the wrist rests on the work surface while operating the mouse in a computer workstation (2-3 hours/day 6 days/week). The alteration was caused by a combination of friction and pressure on the wrist joint tendon due to the faulty positioning of the hand and wrist. This is the normal resting position for the wrist (inclined towards the ulnar side), and is thus the most natural position to adopt. The reported alteration, which responded to a short period of rest and treatment with non-steroid anti-inflammatory drugs for 2-3 days, is described as an example of common injury caused by an unusual faulty posture of the hand. The preventive measures suggested to avoid the occurrence of this type of injury include: (i) instead of resting the weight of the hand on the ulnar side of the wrist it should be distributed between the two pads of fatty tissue which form the base of the palm, (ii) the mouse button could be clicked with the third finger instead of the index finger in order to avoid the tendency of hand to roll into the faulty rest position. PMID- 1461194 TI - [Sudden death caused by freon 22?]. AB - Case report of a plumber's fatal work accident. Investigations on the causes of death made at post mortem showed that the worker had absorbed a large quantity of freon 22 (chlorodifluoromethane) which is known to be a narcotic agent and capable of inducing cardiac arrhythmia. It is believed freon inhalation was the cause of loss of consciousness with consequent death from drowning in the water issuing from the pipes. It is concluded that preventive measures need to be reinforced by adequate information to the workforce on the risks connected to this type of gas. PMID- 1461195 TI - [A systeM of occupational tumor registration: experience of the National INCA]. PMID- 1461196 TI - Current status of physical measurements of the skeleton. AB - An overview is presented of some of the major methods of measuring the skeleton in the past 30 years. These include single photon absorptiometry (SPA), dual photon absorptiometry (DPA), quantitative computed tomography (QCT), and recently dual energy radiographic absorptiometry (DRA), also called DEXA (dual energy x ray absorptiometry). In addition to these methods, all attempting to measure bone mineral density, regional and total body calcium have been determined by in vivo neutron activation analysis (IVNAA). An attempt to determine bone quality as contrasted with bone quantity has been made using ultrasound, with measurements of speed of sound and of attenuation as useful parameters to characterize bone tissue. While the various methods for measuring bone density have been most useful, no one method includes all the features required to be entirely satisfactory: excellent precision and accuracy and the ability to measure volumetric density in gm/cm3. Least successful has been the ability to predict fracture risk, an essential goal in helping the patient. PMID- 1461197 TI - Auger electron dosimetry: report of AAPM Nuclear Medicine Committee Task Group No. 6. PMID- 1461198 TI - Biological effects of the Auger emitter iodine-125: a review. Report No. 1 of AAPM Nuclear Medicine Task Group No. 6. AB - The biological implications of Auger electron cascades following inner shell ionization of atoms have been of interest for over 25 years. By virtue of their decay via orbital electron capture and/or internal conversion, several biomedical radionuclides emit numerous low-energy electrons spontaneously. The biological effects of such radionuclides incorporated into tissues cannot be predicted a priori because of the highly localized patterns of energy deposition by the electrons. Results of extensive research using Iodine-125 as a model Auger electron emitter are now available. This article presents an up-to-date review of the physical and radiobiological data on this Auger emitter. Valuable concepts concerning the action of internal Auger emitters are identified phenomenologically, and questions that need to be answered are indicated. The present understanding provides a scientific basis toward estimation of risk associated with Auger emitters used in diagnosis, and suggests potential applications to therapy. PMID- 1461199 TI - Radiation spectra for Auger-electron emitting radionuclides: report No. 2 of AAPM Nuclear Medicine Task Group No. 6. AB - Radiation spectra for radionuclides currently provided by the MIRD Committee and ICRP do not include the very low-energy N- and O-shell Auger electrons. These electrons, emitted in large numbers by radionuclides decaying by electron capture and/or internal conversion, are important for determining the absorbed dose in microscopic volumes. Accordingly, the present AAPM Report employs Monte Carlo computational methods to obtain a self-consistent set of complete radiation spectra for a variety of radionuclides including 55Fe, 67Ga, 99mTc, 111In, 113mIn, 115mIn, 123I, 125I, 193mPt, 195mPt, 201Tl, and 203Pb. Although the conventional spectra provided by MIRD and ICRP are adequate for most dosimetry calculations, the Auger electron spectra provided in this report are recommended for calculating the dose to target volumes < 1 microns in diameter. PMID- 1461200 TI - Analytic microdosimetry for radioimmunotherapeutic alpha emitters. AB - Analytic microdosimetry using Fourier transform techniques has been applied to internal alpha emitters. These techniques need revision and simplification for use with short-lived radionuclides such as those which may be useful for radioimmunotherapy. Analytic methods may have advantages over Monte Carlo methods in some cases (e.g., where time is important). Applications to eight different source geometries show the usefulness of these techniques. Comparisons of some of the results of Monte Carlo calculations prove its accuracy. For a uniform source of 5.867-MeV alphas spread throughout the volume outside a cell surface, the two methods agree well. Results are within 1% both for the average specific energy and for the number of hits. Analytic microdosimetry provides an alternate method to use for the critical evaluation of models that seek to predict the relation between alpha energy deposition and cell survival data. Similarly, it may be helpful to point the way toward the rational interpretation of general biological results for antibodies labeled with alpha emitters. PMID- 1461201 TI - Microbeam radiation therapy. AB - It is proposed to carry out radiotherapy and radiosurgery for brain lesions by crossfiring an array of parallel, closely spaced microbeams of synchrotron generated x rays several times through an isocentric target, each microbeam in the array having an approximately 25-microns-wide adjustable-height rectangular cross section. The following inferences from the known tissue sparing of 22-MeV deuteron microbeams in the mouse brain and the following exemplary Monte Carlo computations indicate that endothelial cells in the brain that are lethally irradiated by any microbeam in an array of adequately spaced microbeams outside an isocentric target will be replaced by endothelial cells regenerated from microscopically contiguous, minimally irradiated endothelium in intermicrobeam segments of brain vasculature. Endothelial regeneration will prevent necrosis of the nontargeted parenchymal tissue. However, neoplastic and/or nonneoplastic targeted tissues at the isocenter will be so severely depleted of potentially mitotic endothelial and parenchymal cells by multiple overlapping microbeams that necrosis will ensue. The Monte Carlo computations simulate microbeam irradiations of a 16-cm diameter, 16-cm-long cylindrical human head phantom using 50-, 100-, and 150-keV monochromatic x rays. PMID- 1461202 TI - A finite-size pencil beam model for photon dose calculations in three dimensions. AB - A three-dimensional dose computation model employing a finite-size, diverging, pencil beam has been developed and is demonstrated for Cobalt-60 gamma rays. The square cross-section pencil beam is simulated in a semi-infinite water phantom by convolving the pencil beam photon fluence with the Monte Carlo point dose kernel for Cobalt-60. This finite-size pencil beam is calculated one time and becomes a new data base with which to build larger beams by two-dimensional superposition. The pencil beam fluence profile, angle correction for beam divergence, the Mayneord inverse square correction, radial and angular sampling rates, error propagation, and computation time have been investigated and are reported. Radial and angular sampling rates have a great effect on accuracy and their appropriate selection is important. Percent depth doses calculated by finite-size pencil beam superposition are within 1% of values calculated by full convolution and the agreement with values from the literature is within 6%. The latter disagreement is shown to be due to a low-energy photon component which is not modeled in other calculations. Computation time measurements show the pencil beam method to be faster than full convolution and one implementation of the differential-scatter air-ratio (dSAR) method. PMID- 1461203 TI - A study of interface effects in 60Co beams using a thin-walled parallel plate ionization chamber. AB - A large plane-parallel ionization chamber has been constructed to investigate interface effects in 60Co beam. The designed geometry yields negligible perturbation from the side walls, as opposed to the large effects existing in commercially available plane-parallel chambers. The chamber has been used to investigate interface phenomena in transition zones using a wide range of elements (Z = 4-82) as front- and back-scattering media and a clinically relevant 60Co gamma-ray field size. The effects of varying the chamber height discretely (0.5-11 mm) and increasing the wall thickness (1-9 mg/cm2) have been investigated. The variation of the measured ionization with the experimental setup (air gap between backscatter material and chamber wall, measurements at dmax and at 5-cm depth, varying the material both in front of and behind the chamber, etc.) has also been investigated. The simple geometry of the ion chamber has been found optimum for benchmark studies of Monte Carlo calculations. The ion chamber is suited for investigating experimentally the effects of varying transport parameters used in Monte Carlo simulations. The results presented show that the complex physical mechanisms governing 60Co interface dosimetry still make Monte Carlo condensed-history (macroscopic) techniques uncertain. It has been found that the EGS4 Monte Carlo system, together with the user code DOSRZ V4.0 and the PRESTA algorithm, yields good agreement with experiments for low and medium Z (main interest in dosimetry and radiotherapy), but may underestimate up to 10% the backscatter from high-Z materials even when transport parameters are optimized. PMID- 1461204 TI - Simple calculation of the electron-backscatter factor. AB - The authors have studied the dependence of the electron-backscatter factor (EBF) on mean electron energy and on backscatterer atomic number by using the semiempirical depth-dose code EDMULT. A plane-parallel electron beam is assumed to be normally incident on a polystyrene slab, which is backed with a layer (backscatterer) of different materials of effectively semi-infinite thickness. A small air cavity to measure ionization is embedded in the polystyrene slab at the boundary facing the backscatterer. The EBF is defined as the ratio of the ionization with the backscatterer to the ionization with a full polystyrene medium, and is approximated by the ratio of the doses computed at the depth of the cavity. Values of EBF obtained show trends similar to the experimental data of Klevenhagen et al. [Phys. Med. Biol. 27, 263-373 (1982)], although the former are generally lower than the latter. When the typical energy spread of clinical electron beams is taken into account, the difference between the experimental and the calculated values is reduced. The present results also show the same trend of increase of the backscatter factor with increasing energy as observed by Klevenhagen et al. in some series of measurements for the lead backscatterer at the lowest energies. This is explained by the rapid buildup of the dose with depth for electrons of low initial energies incident on the full polystyrene medium. PMID- 1461205 TI - Uncertainty analysis of absorbed dose calculations from thermoluminescence dosimeters. AB - Thermoluminescence dosimeters (TLD) are widely used to verify absorbed doses delivered from radiation therapy beams. Specifically, they are used by the Radiological Physics Center for mailed dosimetry for verification of therapy machine output. The effects of the random experimental uncertainties of various factors on dose calculations from TLD signals are examined, including: fading, dose response nonlinearity, and energy response corrections; reproducibility of TL signal measurements and TLD reader calibration. Individual uncertainties are combined to estimate the total uncertainty due to random fluctuations. The Radiological Physics Center's (RPC) mail out TLD system, utilizing throwaway LiF powder to monitor high-energy photon and electron beam outputs, is analyzed in detail. The technique may also be applicable to other TLD systems. It is shown that statements of +/- 2% dose uncertainty and +/- 5% action criterion for TLD dosimetry are reasonable when related to uncertainties in the dose calculations, provided the standard deviation (s.d.) of TL readings is 1.5% or better. PMID- 1461206 TI - High-energy x-ray beam characterization using photonuclear reaction. AB - Spectral changes in the primary photon beam of a high-energy medical electron accelerator have been monitored using photonuclear reactions. The beam across the radiation field was measured using induced activity in Teflon cylinder and copper foil samples at several off-axis angles, at different SSDs in air and in a solid water phantom. The induced activities of the positron emitters were measured using a coincidence detection system. The experimental results are in agreement with Monte Carlo calculations and Schiff's theory. PMID- 1461207 TI - On the field-size dependence of relative output from a linear accelerator. AB - The radiation output in air on the central axis of a linac photon beam has been modeled as the sum of two components. These are a point source representing radiation direct from the target and a distributed source representing scatter in the flattening filter and primary collimator. By fitting only two parameters, the ratio of the two components for a 20 x 20 field and a width parameter for the distributed source this semi-empirical model describes the relative outputs of square, symmetric rectangular, and asymmetric rectangular fields with an average error of 0.25% for the field sizes studied. PMID- 1461208 TI - Wedge factor dependence on depth and field size for various beam energies using symmetric and half-collimated asymmetric jaw settings. AB - The depth- and field-size dependence of the in-phantom wedge factor have been determined for a Cobalt-60 (Co-60) teletherapy unit and four medical linear accelerators with 4-, 6-, 10-, and 18-MV x-ray beams containing 15 degrees-60 degrees (nominal) lead, brass, and steel wedge filters. Measurements were made with ionization chambers in solid water or water with a source-skin distance of 80 or 100 cm. Field sizes varied from 4 x 4 cm up to a maximum allowable size for each wedge filter. Measurements were performed for symmetric and half-collimated asymmetric fields at depth of maximum dose, 5- and 10-cm depths. For half collimated fields, wedge factor reference points were located at a fixed off-axis distance from the collimator's rotational axis. These systematic measurements on wedges indicate that the wedge factor dependence on depth and field size is a function of beam energy as well as the design of the treatment head and wedge filters. Significance of the results reported herein are discussed for the most commonly used treatment depths and field sizes with various beam energies and wedge filters. PMID- 1461209 TI - A rapid method for electron beam energy check. AB - Assessment of electron beam energy and its long term stability is part of standard quality assurance practice in radiation oncology. Conventional depth ionization or depth-film density measurements are time consuming both in terms of data acquisition and analysis. A procedure is described utilizing ionization measurements at two energy specific depths. It is based on a linear relationship between electron beam energy and its practical range. Energy shifts within the range covered by the two measurement depths are easily resolved. Within a range of +/- 0.50 MeV (+/- 1.30 MeV) around the established mean incident energy of 5.48 MeV (20.39 MeV), the method accuracy is better than 0.10 MeV. PMID- 1461210 TI - Demonstration of megavoltage and diagnostic x-ray imaging with hydrogenated amorphous silicon arrays. AB - Flat-panel imagers consisting of the first large area, self-scanning, pixelated, solid-state arrays made with hydrogenated amorphous silicon (a-Si:H) are under development by the authors for applications in diagnostic x-ray and megavoltage radiotherapy imaging. The arrays, designated by the acronym MASDA for multi element amorphous silicon detector array, consist of a two-dimensional array of a Si:H photodiodes and thin-film transistors and are used in conjunction with scintillating materials. Imagers utilizing MASDA arrays offer a variety of advantages over existing technologies. This article presents initial megavoltage and diagnostic-quality x-ray images taken with several such arrays including the first examples of anatomical-phantom images. The external readout electronics and imaging techniques required to obtain such images are outlined, the construction, operation, and advantages of the arrays briefly reviewed, and the future potential of this new technology discussed. PMID- 1461211 TI - Parametrized x-ray absorption in diagnostic radiology from Monte Carlo calculations: implications for x-ray detector design. AB - The integral dose to the patient and image signal to noise ratio (SNR) are inexorably coupled in x-ray-based diagnostic imaging. Advancements and optimal design of imaging devices need to consider the SNR as well as patient dose. The figure of merit, FOM = (SNR)2/(integral dose), is a useful parameter in optimizing detector designs because it is independent of input exposure, and therefore eliminates exposure as a design consideration. Although numerical calculation of the SNR is relatively straightforward in most cases, the integral dose calculation is made complex due to its scatter component's high dependency on both x-ray energy and patient thickness. Monte Carlo calculations over a range of monoenergetic x-ray energies were used to calculate total energy absorption, and the results are parametrized using polynomial expressions. The results are shown to be applicable to any arbitrary polyenergetic spectrum. An example using the above FOM is given to illustrate the utility of the parametrized results. The parametrized results may prove useful in the computer simulations of x-ray detector systems where the above FOM is utilized. PMID- 1461212 TI - Improvement in specificity of ultrasonography for diagnosis of breast tumors by means of artificial intelligence. AB - A set of ultrasonograms of lesions from 200 patients between the ages of 14 and 93 years who underwent mammography followed by ultrasonographic examination and excisional biopsy has been studied with computer vision techniques to improve the ultrasonographic specificity of the diagnosis. Selected features representing the texture of the lesion were calculated and then classified by an artificial neural network. This network was biased toward correctly classifying all the malignant cases at the expense of some misclassification of the benign cases. The network diagnosed the malignant cases with 100% sensitivity and 40% specificity (compared with 0% specificity for the radiologists diagnosing the same set of cases in the breast imaging setting), and tests performed with a leave-one-out technique indicate that the network will generalize well to new cases. This suggests that methods based on neural network classification of texture features show promise for potentially decreasing the number of unnecessary biopsies by a significant amount in patients with sonographically identifiable lesions. PMID- 1461213 TI - A MRI gradient waveform model for automated sequence calibration. AB - In order to set up magnetic resonance imaging (MRI) procedures of arbitrary voxel dimensions, slice orientation, and sequence timing in a reasonable time, some form of automatic gradient pulse calibration is required. One such method, involving simulation of gradient waveforms, is presented. Waveforms are modeled based on measurements of the step response. The model used divides each transition into three time regions: a "start" region in the first 0.3 ms, a "slew" region, and a "tail" region representing decay of the eddy current compensation error. In the "slew" region, the time derivative of the gradient, G' (t), is expressed as a function of G(t). The first two regions are nonlinear with respect to demand. The mean error in the simulated gradient is generally less than 0.04 mT m-1 in spin echo sequences. Image signal/noise ratios resulting from sequences calibrated using the model are within 5% of those of empirically calibrated sequences. PMID- 1461214 TI - Testing mammography equipment: evolution over a 4-year period. AB - The results of quality control (QC) tests on 70 mammography units in Southern California from 1986 to 1990 are reported. Thirteen facilities, selected because they housed all of the mammography units in three communities involved in a National Institutes of Health research project, had their units tested twice at an interval of 1 year. Fourteen self-selected units were also tested twice at intervals ranging from 1-3 years. Forty-three self-selected units in 31 additional facilities had testing only once. All 70 units underwent measurement of focal spot size or resolution, tube output, half-value layer (HVL), automatic exposure control (AEC) accuracy, relative kVp accuracy, mean glandular dose, and imaging of several test objects. The test results for the units tested once showed no significant differences compared to those tested twice. For the latter, once the units were tested and determined to be acceptable, retesting showed differences only in overall film optical density, dose, and AEC performance. PMID- 1461215 TI - [New perspectives in oncology: is selective destruction of tumor cells with immunotoxins in Hodgkin's disease an additional therapeutic alternative?]. AB - In the present paper, the authors describe the production and testing of immunotoxins for clinical application in Hodgkin's disease. The immunotoxins were constructed by chemical coupling of deglycolysated ricin-A to monoclonal antibodies against antigens on Hodgkin's and Reed-Sternberg cells (CD25, CD30, IRac). The cytotoxic effect of the immunotoxins was investigated in vitro against Hodgkin's and Reed-Sternberg cells (H-RS) and in vivo against solid Hodgkin's tumors in nude mice and disseminated Hodgkin's tumors in SCID mice. Cross reactivity with normal tissue and the staining behaviour observed in sections of Hodgkin's tissue of various subtypes proved important parameters for the assessment of clinical applicability. Of more than 30 evaluated MoAb's, eight immunotoxins were produced, of which six showed both, cytotoxic effects of considerable potency against Hodgkin's tumor cells and low cross-reactivity with vital human organs. The most effective immunotoxin, RFT5 gamma 1.dgA, (CD25) inhibits the growth of H-RS cells at concentrations of 7 pMol and destroys about 60% of solid Hodgkin's tumors of 0.5 cm in diameter in nude mice. This immunotoxin binds to virtually all tumor cells in more than 90% of patients with Hodgkin's disease. Sufficient quantities of RFT5 gamma 1.dgA were produced for the treatment of patients with refractory Hodgkin's disease. These patients are currently being treated in a phase I clinical trial. PMID- 1461216 TI - [Coronary stent implantation: a procedure for treatment of acute dissections after percutaneous transluminal coronary angioplasty]. AB - The development of percutaneous wire-guided endoprostheses (stents) has expanded the possibilities for treating acute vascular occlusion within the field of coronary angioplasty (PTCA). A balloon-expandable Palmaz-Schatz stent was implanted in a total of 14 patients. The coronary arteries involved were the right coronary artery (seven cases), the anterior interventricular branch (five cases), and the circumflex branch (two cases). In seven cases the stent was inserted on an emergency basis to deal with treatening occlusion during PTCA, in one case of occlusion following coronary angiography, and in three cases to recanalize the infarcted vessel. Seven of these eleven patients were submitted to a follow-up angiography three months later, when none was shown to have a restenosis of more than 50%. Stent placement was followed by anticoagulation therapy comprising coumarin combined with acetylsalicylic acid. The Palmaz-Schatz stent represents an alternative to emergency bypass surgery in the treatment of acute dissection during PTCA. PMID- 1461217 TI - [Differential therapy of acute occlusion of leg arteries]. PMID- 1461218 TI - [Polyneuropathy and polyneuritis: clinical aspects, diagnosis and therapy]. PMID- 1461219 TI - [Therapy of acute and chronic viral hepatitis C (non-A, non-B) with interferon alpha]. PMID- 1461220 TI - [The so-called cortisone fear]. PMID- 1461221 TI - [Is cortisone-fear unfounded?]. PMID- 1461222 TI - [56-year-old patient with recurrent lung infiltration and "lung tumor"]. PMID- 1461223 TI - [Anterior ST segment depressions in acute posterior wall infarct]. PMID- 1461224 TI - [Continuing medical education--what will change?]. PMID- 1461225 TI - [Microbiology of Pneumocystis carinii]. PMID- 1461226 TI - [Determinants of serum pentamidine concentration in the human]. AB - By means of serial measurements of pentamidine in plasma, urine and feces the significance of biologically available dose, volume of distribution, elimination and dose interval for serum concentration is investigated in patients with AIDS and bone marrow transplantation after inhaled and intravenous application. Aerosolisation of the drug yields to serum concentration mostly below the detection limit (HPLC). In urine only 0.15 to 0.8% of the substance biologically available in the lung are measured as unaltered pentamidine-base. After i.v. infusion the dose dependent low serum concentrations of 30 to 100 ng/ml indicate a fast distribution in peripheral compartments from which a very slow deliberation is seen. The half-life of the drug is also dose dependent and amounts under clinical conditions at minimum four days. The fecal excretion is found to be only one third of that measured in urine. A difference in the kinetic of elimination between bone marrow transplantated and AIDS-patients could not be evaluated. For clinical therapy the most important pharmacokinetic variable seems to be the terminal elimination constant which would implicate a prolongation of the common dose interval. PMID- 1461227 TI - [Risk factors and prevention of pneumocystis carinii pneumonia after bone marrow transplantation]. AB - For six months after bone marrow transplantation (BMT) there is a risk of 5 to 15% to suffer from interstitial pneumonia due to pneumocystis carinii (PcP). Prophylaxis with trimethoprim/sulfamethoxazol is therefore routinely and successfully applied. However myelotoxicity, allergic reactions, augmentation of the risk of nephrotoxicity with cyclosporine A and noncompliance may be serious problems. Since the prophylaxis of PcP with pentamidine-aerosol proved to be effective in patients with AIDS, we conducted a prospective trial with regular inhalations of pentamidine. The aim of this study was to evaluate the toxicity, safety, practicability and possible resorption of pentamidine when applied as aerosol. The first of 43 patients were treated with 60 mg pentamidine on two days before, at the day of BMT and 14 days after BMT. Starting four weeks after BMT, 300 mg pentamidine were given every four weeks up to six months. After the study, the four 60 mg inhalations were replaced by two 300 mg inhalations before BMT, because this proved to be more convenient for the patients. There was no pneumonia due to pneumocystis carinii. The only noteworthy side effects observed were cough (19.8%), salivation (9.6%) and sore throat (5.7%). In general pentamidine was well tolerated and well accepted by the patients. Pentamidine could only be detected in the serum of 40 to 60% of all patients. In those patients the serum levels were 7.5 to 9 ng/ml and similar to concentrations found in comparable patients with AIDS. We conclude, that pentamidine-aerosol has only minor side effects, is well tolerated and safe and is therefore an attractive alternative for PcP-prophylaxis after BMT. PMID- 1461228 TI - [Pneumocystis carinii pneumonia: a life threatening complication after kidney transplantation]. AB - Aggressive immunosuppression in kidney transplantation increases the risk of opportunistic infections. We report ten cases of pneumocystis carinii pneumonia in a group of 420 kidney recipients (2.1%). All patients showed a severe- hyperacute--course of the infection. One patient required mechanical ventilation. In all cases the diagnosis could be established applying fibreoptic bronchoscopy with lavage and partly using transbronchial biopsy. The therapy consisted of intravenous cotrimoxazole and inhalation of pentamidine. All patients survived even after severe course of the disease. Graft explantation for saving patients was not necessary. PMID- 1461229 TI - [Pentamidine inhalation in prevention of pneumocystis carinii pneumonia in treatment of rejection with monoclonal antibody Orthoclone (OKT-3)]. AB - The use of the monoclonal antibody OKT-3 (Orthoclone) is associated with an increased risk of pneumocystis carinii pneumonia. In a retrospective study, the efficiency of a prophylactic inhalation of pentamidine during acute renal allograft rejection therapy with OKT-3 was investigated. From July 1988 until October 1989 32 renal transplanted patients with acute rejection refractory to steroids had been treated with OKT-3. Twelve of the patients developed a pneumonia (four pneumococcus, one klebsiella, one cytomegalovirus), in six cases, a pneumocystis carinii infection was diagnosed in the bronchial lavage. Four of these patients with pneumocystis carinii pneumonia died despite high dose treatment with cotrimoxazole. From November 1989, a prophylactic inhalation of pentamidine was performed during acute renal allograft rejection therapy with OKT 3. From 33 patients, in eleven cases, a pneumonia was diagnosed (three pneumococcus, one klebsiella, two legionella, three cytomegalovirus, one candida), one patient developed a pneumocystis carinii pneumonia, which was successfully treated with cotrimoxazole. No patient in this group died because of pulmonary infection. The results suggest, that a prophylactic inhalation of pentamidine in severely immunosuppressed solid organ transplant recipients can prevent pneumocystis carinii pneumonia. PMID- 1461230 TI - [Pneumocystis carinii in oncologic diseases]. PMID- 1461231 TI - [The effect of rigid fixation on bone growth: a radiologic study in the rabbit]. AB - The rigid fixation with plates represents an useful aid in the treatment of the maxillofacial diseases. To the best of our knowledge no studies on the effects of the plates placed across the growing fronto-nasal suture are available. We have therefore examined these effects in an experimental model represented by the suture of eight rabbits. The surgical procedure consists of placing one microplate and four screws across the frontonasal suture of each rabbit, one month old. Radiographies were made both at the moment of the operation and after thirty days. Our results demonstrate a decrease of the normal growth of the suture stressed by plates. PMID- 1461232 TI - [Lingual thyroid]. AB - Lingual thyroid is a rare occurrence in oral surgical practice. A case is reported accompanied by a current view of the presions literature. A brief resume of methods of treatment is given and the importance of investigations before excision is emphasised. PMID- 1461233 TI - [A parotid arteriovenous fistula of nontraumatic origin. A case report]. AB - The authors report their experience of a case of non traumatic arteriovenous communication of the parotid region in an adult subject. They confirm that its manifestations in grown-ups are to be linked with an inactive angiodysplastic field. The diagnostic approaches in the face of a hybrid symptomatology and the therapeutic choices are described. Moreover, an aesthetically and functionally efficient surgical correction is proposed. PMID- 1461234 TI - [A spindle-cell carcinoma of the oral mucosa. A case report]. AB - Spindle cell carcinoma is a relatively rare tumor which occurs often in the upper respiratory tract, the oral cavity, and in the esophagus and skin. In this paper a patient who presented a tumor mass of the lover gingiva which was subsequently diagnosed as a spindle cell carcinoma is reported. The clinicopathologic aspects and diagnostic problems of this unusual tumor of the oral mucosa are discussed. PMID- 1461235 TI - [Prosthetic rehabilitation in patients with malignant tumors of the soft palate. A clinical case report]. AB - Soft palate neoplasms are relatively rare and their care requires not only an adequate surgical removal but also a post-treatment rehabilitation. In this article the authors after having considered the importance of the soft palate function on the individual's ability to shallow and speak, describe one case of squamous cell carcinoma of the soft palate and treated with surgery followed by prosthetic rehabilitation. Especially it is pointed out the utility of a palatal obturator in the care of deleterious esthetic and psychological aspect of the residual anatomical defect, considering the possibility of the re-establishment the integrity of the tissues and structures in the oral cavity by hand-made prosthesis more and more exact and functional. PMID- 1461236 TI - [Myelolipomatosis. A report of a case located in the mandible]. AB - Myelolipoma is a rare benign tumour involving, in the majority of cases, the adrenal gland. Given the absolute predominance of this localisation, in this report of extra-adrenal localisations of these tumours the authors considered it worthwhile and necessary to refer to the former, relatively more complete series of data, with the exception of the supposed or real differences which exist between the two groups. Myelolipomatosis should not be considered an example of dysplasia, but on the contrary benign metaplasia/hamartoma. It is therefore obvious that, faced with an expansive process of this type, it is vital to obtain a precise diagnosis on which to base the choice of clinical and therapeutic management since this is also influenced by the anatomical site of the tumour. On the basis of a series of pathophysiological parameters, the authors have formulated a diagnostic protocol followed by a therapeutic approach since, in this context, there is no point resorting to a so-called "wait and see" strategy. In addition, the analysis of the above parameters convinced the authors of the possibility that these tumours should be regarded as bodies which should not be separated from the reaction of the organism as a whole to and appropriate stressigenic event persisting over time. PMID- 1461237 TI - [A weight and surface analysis of glass ionomer cements in the presence of acid solutions]. AB - The surface and solubility of some glass ionomer cements have been assessed after exposure to four acids (acetic, formic, lactic and propionic), that are usually present in the bacterial plaque. Therefore, we prepared 80 samples--20 for earl of 4 commercial products; after 7 days and, then after 30 other days, the samples were examined by microscope and weighed. Finally, those showing the most significant modifications were photographed. PMID- 1461239 TI - [AIDS in Italy: an update to 31 December 1991]. PMID- 1461238 TI - [The triennial school of specialization in orthodontics: a final report of the Erasmus Project]. PMID- 1461240 TI - [AIDS in the world to 1 October 1991]. PMID- 1461241 TI - [Total atrophy of the mandibular alveolar crest. A new therapeutic proposal (the use of a tissue expander) and a clinical case report]. AB - Atrophy of the alveolar crest, meant as a syndrome due to a certain variety of pathogenetic episodes developing in a more or less marked framework of resorption of the alveolar to the maxillary processes, represents an issue of debated and uncertain solution, especially in a view of the extreme degrees of the phenomenon. Various kinds of surgical approach have been suggested over time: among them mention should be made of the onlay graft technique, the osteotomy intervention visor type, the osseous interposition sandwich type, and other methods, which were often the result of a pontered mediation of the above mentioned, and which should have therefore enjoyed their single advantages. In consideration of the different techniques, the results were more or less noteworthy and it was clear, however, that a certain "gap" was still existing between the results aimed to and the results reached. Today, thanks to the tissue expander technique, combined with the use of alloplasty materials (hydroxylapatite), we can give a new contribution to the solution of this invalidating pathology, thus reaching more complete and lasting results in the plastic reconstruction of the alveolar crest, and avoiding at the same time the disadvantages, even of iatrogenic kind, of an osteotomy intervention. PMID- 1461242 TI - [Oral lichen planus and liver pathology. I. The prevalence of liver damage in a case load of 96 patients with oral lichen planus]. AB - In order to evaluate if oral lichen planus (OLP) may be regarded as a marker of even unknown liver disease, 96 incident OLP cases were screened through anamnestic, laboratory, instrumental investigations and gastroenterology consultation. The frequency of hepatopathies was 23/96 (24%): 7 had cirrhosis, 3 had chronic active hepatitis, 2 had chronic persistent hepatitis, 10 steatosis and 1 had undetermined liver disease. Eleven of these 23 patients (48%) had unknown hepatopathies, although five of them had severe liver disorders (cirrhosis, chronic hepatitis). Forty-four of 73 patients without definite liver disorders (60%) had at least one abnormal liver parameter. This results confirm frequent association of OLP with hepatic damage and moreover it shown that OLP may be an important clinical sign of symptomless hepatopathies. PMID- 1461243 TI - [Oral lichen planus and liver pathology. II. The clinico-statistical correlations between oral manifestations and liver damage]. AB - To characterize with more precision the association between oral lichen planus (OLP) and hepatopathies, 96 patients with OLP were separated in two groups ordered by presence or absence of liver diseases comparing some variables (age, sex, presence of pain, clinical variety, presence of skin lesions, alcohol consumption and exposure to drugs inducing hepatic injury) and evaluating the statistical significance. Factors associated with increased frequency of liver diseases were erosive variety of OLP (p = 0.024) and presence of pain (p = 0.026) (chi square test with Yates correction). It's confirmed that OLP patients with higher risk of liver disease are those that have erosive lesions with severe symptoms and often diffused in the entire oral cavity; furthermore, it's highlighted that the probability to find liver disease associated with reticular and plaque-like form of OLP is low, but not negligible. PMID- 1461244 TI - [Lipoma of the tongue. A clinical case report]. AB - Lipoma is a benign tumor of the adipose tissue. It is a common neoplasm but very rarely involves the tongue. Only 0.3% of all tumors involving the tongue are lipomas. A case of lipoma originating in the tongue is described. The tumor was removed and did not recur one year after excision. PMID- 1461245 TI - [Cervicofacial actinomycosis. A case study]. AB - A case of cervicofacial actinomycosis, sited in the central hyoid region, is reported. The Authors have emphasized the difficulties of the diagnosis. It's very important hat the clinical diagnosis of actinomycotic infection be confirmed by a positive culture test. Actinomycosis can be suspected if multiple recurrent pustular swellings are present, associated with any trauma or teeth extractions. PMID- 1461246 TI - [Dermoid cysts of the mouth floor. A case report]. AB - We report a large submandibular dermoid cyst located laterally at the floor of the mouth. Classification, etiopathogenesis, positive and differential diagnosis, treatment and prognosis are discussed. This anomaly is an infrequent congenital disorder that usually becomes apparent during the second or third decade of life. Prognosis is excellent after correct surgical treatment. PMID- 1461247 TI - [Oral candidiasis as the first manifestation of HIV (human immunodeficiency virus) infection. An analysis of 2 cases]. AB - The authors report two cases in which unexplained oral candidiasis led to the diagnosis of HIV infection with clinical form of AIDS-related complex (ARC). It is highlighted that the dentist showed investigate the causes of every unexplained oral candidiasis in adult because this opportunist infection may be the first sign of immunosuppression associated with AIDS and AIDS-related syndromes. PMID- 1461248 TI - [The use of kinesiography and electromyography in assessing the outcome of a fracture of the mandibular condyles]. AB - The purpose of this work is to consider the sensibility, reliability, and utility of the computerized electromyography and kinesiography in the diagnosis and study of the functional results in patients affected of single or bilateral previous fractures of the condyles. The Authors analyse three clinical parameters and compare them with thirteen parameters gathered from the computerized data and the kinesiogram and electromyogram analysis of a selected sample of thirteen patients with previous fractures of the condyles. This comparison has shown the greatest reliability and sensibility (a larger quantity of instrumental data as regards the clinical checkup and absence of false negative diagnosis) of these techniques with regard to ordinary clinical checkup. Furthermore the features of objectivity, non invasion and easy repetition, indicate that computerized electromyography and kinesiography play an important role in the diagnosis and study of the functional results of fractures of the condyles and in the follow-up examination. PMID- 1461249 TI - Unintended childbearing: pregnancy risk assessment monitoring system--Oklahoma, 1988-1991. AB - Unintended pregnancies may be associated with delays in the initiation of prenatal care and behaviors during pregnancy that increase the risk for adverse birth outcomes (1,2). Based on estimates from the 1988 National Survey of Family Growth, 28% of births were mistimed during the 3-4 years before the survey, and 12% were unwanted (3). In Oklahoma, family-planning services are provided as an element of the state's maternal and child health program efforts, and the state has made a priority of identifying mothers at high risk for unintended pregnancy. This report summarizes an analysis of data from the Oklahoma Pregnancy Risk Assessment Monitoring System (PRAMS) to assess the risk for unintended childbearing in Oklahoma during 1988-1991. PMID- 1461250 TI - Abortion surveillance: preliminary data--United States, 1990. AB - For 1990, CDC received data on legal induced abortions from 52 reporting areas: 50 states, New York City, and the District of Columbia. This report presents preliminary data for 1990. PMID- 1461251 TI - Update: influenza activity--United States and worldwide, 1992-93 season. AB - Influenza activity in the United States is monitored by CDC through surveillance systems maintained cooperatively with state and local health departments (1); in addition, CDC receives reports of worldwide influenza activity from international World Health Organization (WHO) collaborating laboratories and from WHO, Geneva. This report summarizes surveillance for influenza in the United States and worldwide during the 1992-93 season through December 5, 1992. PMID- 1461252 TI - Selected behaviors that increase risk for HIV infection, other sexually transmitted diseases, and unintended pregnancy among high school students--United States, 1991. AB - Since the 1970s, sexual activity has increased among adolescents in the United States (1); at the same time, rates of sexually transmitted diseases (STDs) (1), unintended pregnancy (2), and--beginning in the 1980s--human immunodeficiency virus (HIV) infection (3,4) also have increased among adolescents. This report presents 1991 self-reported data from students in grades 9-12 about behaviors that can result in HIV infection, other STDs, or unintended pregnancy. PMID- 1461253 TI - Availability of sulfadiazine--United States. PMID- 1461254 TI - Imported human rabies--France, 1992. AB - Wildlife rabies has been enzootic in France since 1968; however, 13 of the 14 human cases in France were imported, and one was in a person infected through a corneal transplant (1). On May 9, 1992, a 3-year-old boy who resided in Algeria died from rabies encephalitis in Paris. This report summarizes the investigation of this case by the Pasteur Institute. PMID- 1461255 TI - Regulation of Ca2+ release from sarcoplasmic reticulum in skeletal muscles. AB - Ca2+ release from skeletal sarcoplasmic reticulum (SR) could be regulated by at least three mechanisms: 1) Ca2+, 2) calmodulin, and 3) Ca2+/calmodulin-dependent phosphorylation. Bell-shaped Ca(2+)-dependence of Ca2+ release from both actively and passively-loaded SR vesicles suggest that opening and closing of the Ca2+ release channel could be regulated by [Ca2+o]. The time- and concentration dependent inhibition of Ca2+ release from skeletal SR by calmodulin was also studied using passively-Ca2+ loaded SR vesicles. Up to 50% of Ca2+ release was inhibited by calmodulin (0.01-0.5 microM); this inhibition required 5-15 min preincubation time. The hypothesis that Ca2+/calmodulin-dependent phosphorylation of a 60 kDa protein regulates Ca2+ release from skeletal SR was tested by stopped flow fluorometry using passively-Ca2+-loaded SR vesicles. Approximately 80% of the initial rates of Ca(2+)-induced Ca2+ release was inhibited by the phosphorylation within 2 min of incubation of the SR with Mg-ATP and calmodulin. We identified two types of 60 kDa phosphoproteins in the rabbit skeletal SR, which was distinguished by solubility of the protein in CHAPS. The CHAPS-soluble 60 kDa phosphoprotein was purified by column chromatography on DEAE-Sephacel, heparin-agarose, and hydroxylapatite. Analyses of the purified protein indicate that the CHAPS-soluble 60 kDa protein is an isoform of phosphoglucomutase (PGM). cDNAs encoding isoforms of PGM were cloned and sequenced using synthetic oligonucleotides. Two types of PGM isoforms (Type I and Type II) were identified. The translated amino acid sequences show that Type II isoform is SR form.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461256 TI - Incorporation of 3H-N-ethylmaleimide into sheep red cell membrane thiol groups following protection by diamide-induced oxidation. AB - The thiol oxidant diazene dicarboxylic acid bis [N,N-dimethylamide] (diamide) is known to reversibly activate K-Cl cotransport in sheep red blood cells. Although the detailed mechanism of activation is unknown, functional thiols at the membrane or at the cytoplasmic level are recognized as important. To search for membrane bound thiols involved in the regulation of K-Cl cotransport, sheep red cells were first exposed to diamide at concentrations activating K-Cl cotransport, and then to the alkylating agent N-ethylmaleimide (NEM) in order to block non-oxidized thiols. White ghosts, prepared by osmotic lysis from these cells, were again treated with NEM followed by reduction of the diamide-induced dithiols with dithiothreitol (DTT) concentrations known to reverse the diamide induced K-Cl flux. Maximum 3H-NEM incorporation into the DTT-reduced thiols occurred at 50 microM DTT. Saturation labelling by 3H-NEM of about 2 x 10(4) diamide-protected thiols/cell occurred at 25 microM NEM. Diamide protected about 0.1% of all membrane thiols chemically determined earlier. Membranes from high K (HK) and low K (LK) sheep red cells did not differ significantly in the number of diamide-protected thiols, and polyacrylamide gels revealed a similar protein distribution of 3H-NEM-labelled thiols. Since diamide is known to stimulate K-Cl flux in LK cells ten times more than in HK cells this finding is consistent with the hypothesis of a cytoplasmic control effecting different K-Cl flux activities in the membranes of the two cation genotypic red blood cells. PMID- 1461257 TI - Influence of tight junctions on the interaction of salts with lingual epithelia: responses of chorda tympani and lingual nerves. AB - The role of tight junctions in modulating responses from chorda tympani (taste) and lingual (general sensory) nerves are clarified in regard to their responses to salts. Chorda tympani (CT) responses elicited by organic sodium salts require greater Na+ concentrations to elicit the same magnitude of response as NaCl. These data can be understood in terms of the organic anions (compared with Cl-) producing larger liquid-junction potentials across tight junctions between taste cells which, in turn, reduces Na+ influx into taste cells via amiloride inhibitable channels. The anion contribution to the CT response to different Na+ salts can be eliminated (or enhanced) by voltage clamping the tongue with negative (with respect to the serosal solution) potentials. Whole nerve recordings from the lingual branch of the trigeminal nerve elicited by NaCl (and other salts) were reversibly inhibited by the tight junction blocker, LaCl3. These data suggest that small hydrophilic molecules elicit responses from trigeminal fibers by diffusing across tight junctions between epithelial cells and altering the composition of the extracellular space. PMID- 1461258 TI - Probing the structure of the Neurospora crassa plasma membrane H(+)-ATPase. AB - The structure of the Neurospora crassa plasma membrane H(+)-ATPase has been investigated using a variety of chemical and physiochemical techniques. The transmembrane topography of the H(+)-ATPase has been elucidated by a direct, protein chemical approach. Reconstituted proteoliposomes containing purified H(+) ATPase molecules oriented predominantly with their cytoplasmic surface facing outward were treated with trypsin, and the numerous peptides released were purified by HPLC and subjected to amino acid sequence analysis. In this way, seventeen released peptides were unequivocally identified as located on the cytoplasmic side of the membrane, and numerous intervening segments could be inferred to be cytoplasmically located by virtue of the fact that they are too short to cross the membrane and return between sequences established to be cytoplasmically located. Additionally, three large membrane-embedded segments of the H(+)-ATPase were isolated using our recently developed methods for purifying hydrophobic peptides, and identified by amino acid sequence analysis. This information established the topographical location of virtually all of the 919 residues in the H(+)-ATPase molecule, allowing the formulation of a reasonably detailed model for the transmembrane topography of the H(+)-ATPase polypeptide chain. Separate studies of the cysteine chemistry of the H(+)-ATPase have demonstrated the existence of a single disulfide bridge in the molecule, linking the NH2- and COOH-terminal membrane-embedded domains. And, analyses of the circular dichroism and infrared spectra of the purified H(+)-ATPase have elucidated the secondary structure composition of the molecule. A first generation model for the tertiary structure of the H(+)-ATPase based on this information and other considerations is presented. PMID- 1461259 TI - Regulation of the skeletal sarcoplasmic reticulum Ca(2+)-ATPase by phospholamban and negatively charged phospholipids in reconstituted phospholipid vesicles. AB - The Ca(2+)-ATPase of skeletal sarcoplasmic reticulum was purified and reconstituted in proteoliposomes containing phosphatidylcholine (PC). When reconstitution occurred in the presence of PC and the acidic phospholipids, phosphatidylserine (PS) or phosphatidylinositol phosphate (PIP), the Ca(2+) uptake and Ca(2+)-ATPase activities were significantly increased (2-3 fold). The highest activation was obtained at a 50:50 molar ratio of PS:PC and at a 10:90 molar ratio of PIP:PC. The skeletal SR Ca(2+)-ATPase, reconstituted into either PC or PC:PS proteoliposomes, was also found to be regulated by exogenous phospholamban (PLB), which is a regulatory protein specific for cardiac, slow twitch skeletal, and smooth muscles. Inclusion of PLB into the proteoliposomes was associated with significant inhibition of the initial rates of Ca(2+)-uptake, while phosphorylation of PLB by the catalytic subunit of cAMP-dependent protein kinase reversed the inhibitory effects. The effects of PLB on the reconstituted Ca(2+)-ATPase were similar in either PC or PC:PS proteoliposomes, indicating that inclusion of negatively charged phospholipid may not affect the interaction of PLB with the skeletal SR Ca(2+)-ATPase. Regulation of the Ca(2+)-ATPase appeared to involve binding with the hydrophilic portion of phospholamban, as evidenced by crosslinking experiments, using a synthetic peptide which corresponded to amino acids 1-25 of phospholamban. These findings suggest that the fast-twitch isoform of the SR Ca(2+)-ATPase may be also regulated by phospholamban although this regulator is not expressed in fast-twitch skeletal muscles. PMID- 1461260 TI - Calcium entry in rat parotid acinar cells. PMID- 1461261 TI - Changes in adrenergic receptors during the development of heart failure. AB - Moderate and severe stages of congestive heart failure due to the loss of myocardium upon coronary occlusion in rats was associated with an increase in alpha-adrenergic receptors and a decrease in beta-adrenergic receptors in the viable left ventricle. However, at early stages of heart failure the number of beta-adrenergic receptors was decreased without any changes in the number of alpha-adrenergic receptors. The affinities of these receptors to alpha receptor antagonist (3H-prazosin) and beta receptor antagonist (3H-dihydroalprenolol) were not altered in the failing hearts. On the other hand, the pattern of changes in both alpha- and beta-adrenergic receptors in heart membranes treated with oxygen free radical generating system was different from that seen in the failing hearts. In particular, the affinities for these receptors were decreased whereas the number of beta-receptors was increased and the number of alpha-receptors was decreased or unchanged. These results indicate that alterations in the adrenergic receptors in heart failure are not due to the formation of oxygen free radicals. PMID- 1461263 TI - War against famine, for nutrition. AB - In Somalia, the world is fighting an unprecedented war in the name of basic nutrition. In the United States, the government has gone overboard on the matter of nutrition and health. PMID- 1461262 TI - Magnesium homeostasis in cardiac cells. AB - Several aspects of Mg2+ homeostasis were investigated in cultured chicken heart cells using the fluorescent Mg2+ indicator, FURAPTRA. The concentration of cytosolic Mg2+ ([Mg2+]i) is 0.48 +/- 0.03 mM (n = 31). To test whether a putative Na/Mg exchange mechanism controls [Mg2+]i below electrochemical equilibrium, we manipulated the Na+ gradient and assessed the effects on [Mg2+]i. When extracellular Na+ was removed, [Mg2+]i increased; this increase was not altered in Mg-free solutions, but was attenuated in Ca-free solutions. A similar increase in [Mg2+]i, which was dependent upon extracellular Ca2+, was observed when intracellular Na+ was raised by inhibiting the Na/K pump with ouabain. These results do not provide evidence for Na/Mg exchange in heart cells, but they suggest that Ca2+ can modulate [Mg2+]i. In addition, removing extracellular Na+ caused a decrease in intracellular pH (pHi), as measured by pH-sensitive microelectrodes, and this acidification was attenuated when Ca2+ was also removed from the solution. These results suggest that Ca2+ and H+ interact intracellularly. Since changes in the Na+ gradient can also alter pHi, we questioned whether pH can modulate [Mg2+]i. pHi was manipulated by the NH4Cl prepulse method. NH4(+)-evoked changes in pHi, as measured by the fluorescent indicator BCECF, were accompanied by opposite changes in [Mg2+]i; [Mg2+]i changed by -0.16 mM/unit pH. These NH4(+)-evoked changes in [Mg2+]i were not caused by movements of Mg2+ or Ca2+ across the sarcolemma or by changes in cytosolic Ca2+. Additionally, pHi was manipulated by changing extracellular pH (pHo).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461264 TI - New human gene therapy institute in Pennsylvania. PMID- 1461266 TI - Hughes looks east for next expansion. PMID- 1461265 TI - Proposal opens debate over US data on animals. PMID- 1461267 TI - Genuine genius. PMID- 1461268 TI - More on legumes. PMID- 1461269 TI - Germane reviews. PMID- 1461270 TI - Nordic science. PMID- 1461271 TI - Change at the Karolinska. PMID- 1461272 TI - Merging for strength. PMID- 1461273 TI - No biotechnology bandwagon. PMID- 1461274 TI - Of mice and the MHC. PMID- 1461275 TI - Muscle development. Running without regulators. PMID- 1461276 TI - Deviant TATA-box binding protein. PMID- 1461277 TI - More on motor neurons. PMID- 1461278 TI - Per--no link to gap junctions. PMID- 1461279 TI - Communal nesting patterns in mice implicate MHC genes in kin recognition. AB - House mice (Mus musculus domesticus) form communal nests and appear to nurse each other's pups indiscriminately. Communal nesting probably functions to reduce infanticide, but it also makes females vulnerable to exploitation if nursing partners fail to provide their fair share of care. Kinship theory predicts that females will preferentially form communal nests with relatives to minimize exploitation and further increase inclusive fitness. Here we provide evidence from seminatural populations that females prefer communal nesting partners that share allelic forms of major histocompatibility complex genes. Such behaviour would lead to the selection of close relatives as communal nesting partners. Although criteria for the demonstration of kin recognition are currently embroiled in controversy, this is the first vertebrate study to meet Grafen's restrictive requirements: discrimination is based on genetic similarity at highly polymorphic loci, incidental correlations due to relatedness are experimentally controlled, and strong reasons exist for expecting the assayed behaviour to be kin-selected. PMID- 1461280 TI - The perception of heading during eye movements. AB - When a person walks through a rigid environment while holding eyes and head fixed, the pattern of retinal motion flows radially away from a point, the focus of expansion (Fig. 1a). Under such conditions of translation, heading corresponds to the focus of expansion and people identify it readily. But when making an eye/head movement to track an object off to the side, retinal motion is no longer radial (Fig. 1b). Heading perception in such situations has been modelled in two ways. Extra-retinal models monitor the velocity of rotational movements through proprioceptive or efference information from the extraocular and neck muscles and use that information to discount rotation effects. Retinal-image models determine (and eliminate) rotational components from the retinal image alone. These models have been tested by measuring heading perception under two conditions. First, observers judged heading while tracking a point on a simulated ground plane. Second, they fixated a stationary point and the flow field simulated the effects of a tracking eye movement. Extra-retinal models predict poorer performance in the simulated condition because the eyes do not move. Retinal-image models predict no difference in performance because the two conditions produce identical patterns of retinal motion. Warren and Hannon observed similar performance and concluded that people do not require extra-retinal information to judge heading with eye/head movements present, but they used extremely slow tracking eye movements of 0.2-1.2 deg s-1; a moving observer frequently tracks objects at much higher rates (L. Stark, personal communication). Here we examine heading judgements at higher, more typical eye movement velocities and find that people require extra-retinal information about eye position to perceive heading accurately under many viewing conditions. PMID- 1461281 TI - Three-dimensional illusory contours and surfaces. AB - Under general viewing conditions, objects are often partially camouflaged, obscured or occluded, thereby limiting information about their three-dimensional position, orientation and shape to incomplete and variable image cues. When presented with such partial cues, observers report perceiving 'illusory' contours and surfaces (forms) in regions having no physical image contrast. Here we report that three-dimensional illusory forms share three fundamental properties with 'real' forms: (1) the same forms are perceived using either stereo or motion parallax cues (cue invariance); (2) they retain their shape over changes in position and orientation relative to an observer (view stability); and (3) they can take the shape of general contours and surfaces in three dimensions (morphic generality). We hypothesize that illusory contours and surfaces are manifestations of a previously unnoticed visual process which constructs a representation of three-dimensional position, orientation and shape of objects from available image cues. PMID- 1461282 TI - Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle. AB - Dystrophin is associated with a complex of muscle membrane (sarcolemmal) glycoproteins that provide a linkage to the extracellular matrix protein, laminin. The absence of dystrophin leads to a dramatic reduction of the dystrophin-associated proteins (156DAG, 59DAP, 50DAG, 43DAG and 35DAG) in the sarcolemma of patients with Duchenne muscular dystrophy and mdx mice. Here we demonstrate that dystrophin-related protein (DRP, utrophin), an autosomal homologue of dystrophin, is associated with an identical or antigenically similar complex of sarcolemmal proteins and that DRP and the dystrophin/DRP-associated proteins colocalize to the neuromuscular junction in Duchenne muscular dystrophy and mdx muscle. The DRP and dystrophin/DRP-associated proteins are found throughout the sarcolemma in small-calibre skeletal muscles and cardiac muscle of adult mdx mice. Because these muscles show minimal pathological changes, our results could provide a basis for the upregulation of DRP as a potential therapeutic approach. PMID- 1461283 TI - Primary structure of dystrophin-related protein. AB - Dystrophin-related protein (DRP or 'utrophin') is localized in normal adult muscle primarily at the neuromuscular junction. In the absence of dystrophin in Duchenne muscular dystrophy (DMD) patients, DRP is also present in the sarcolemma. DRP is expressed in fetal and regenerating muscle and may play a similar role to dystrophin in early development, although it remains to be determined whether DRP can functionally replace dystrophin in adult tissue. Previously we described a 3.5-kilobase complementary DNA clone that exhibits 80 per cent homology to the C-terminal domain of dystrophin. This sequence identifies a 13-kilobase transcript that maps to human chromosome 6 (refs 2, 11). Antibodies raised against the gene product identify a polypeptide with a relative molecular mass of about 400K in all tissues examined. To investigate the relationship between DRP and dystrophin in more detail, we have cloned and sequenced the whole DRP cDNA. Homology between DRP and dystrophin extends over their entire length, suggesting that they derive from a common ancestral gene. Comparative analysis of primary sequences highlights regions of functional importance, including those that may mediate the localization of DRP and dystrophin in the muscle cell. PMID- 1461284 TI - Raf functions downstream of Ras1 in the Sevenless signal transduction pathway. AB - Specification of the R7 cell fate in the developing Drosophila eye requires activation of the Sevenless (Sev) receptor tyrosine kinase, located on the surface of the R7 precursor cell, by its interaction with the Boss protein, expressed on the surface of the neighbouring R8 cell. Four genes that participate in the intracellular transmission of this signal have so far been identified and molecularly characterized: Ras1, Sos, Gap1 and sina (refs 4-8). The Drosophila homologue of the mammalian Raf-1 serine/threonine kinase, which has been implicated in signal transduction pathways activated by many receptor tyrosine kinases (reviewed in refs 9 and 10), is encoded by the raf locus (also known as l(1)polehole, Draf-1 or Draf). Here we show that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function. We also present genetic evidence suggesting that Raf acts downstream of Ras1 and upstream of Sina in this signal transduction cascade. PMID- 1461285 TI - SEC21 is a gene required for ER to Golgi protein transport that encodes a subunit of a yeast coatomer. AB - Non-clathrin coated vesicles have been implicated in early steps of intercompartmental transport. A distinct set of coat proteins are peripherally associated with the exterior of purified mammalian intra-Golgi transport vesicles. The 'coatomer', a cytosolic complex containing a similar subunit composition to and sharing at least one subunit (beta-COP) with the coat found on vesicles, has been postulated to be the precursor of this non-clathrin coat. Here we describe the characterization of SEC21, an essential gene required for protein transport from the endoplasmic reticulum to the Golgi in the yeast Saccharomyces cerevisiae. The 105K product of this gene, Sec21p, participates in a cytosolic complex that we show to be a yeast homologue of the mammalian coatomer. These observations demonstrate that a non-clathrin coat protein plays an essential role in intercompartmental transport. PMID- 1461286 TI - Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C. PMID- 1461287 TI - [Prevention of central nervous system hemorrhages in patients with hemophilia]. PMID- 1461288 TI - [Nobel Prize for the discovery of protein modification]. PMID- 1461289 TI - [Opioids and chronic benign pain]. PMID- 1461290 TI - [Is prescribing of opioid analgetics such as morphine to patients with chronic benign pain (un)ethical?]. PMID- 1461291 TI - [Habitual mouth breathing]. PMID- 1461292 TI - [How much information is retained by participants in clinical trials?]. AB - OBJECTIVE: To assess which information participants of the Dutch TIA trial could remember from the informed consent procedure. DESIGN: Descriptive investigation. SETTING: The University Hospital Utrecht and the University Medical Centre Amsterdam. METHODS: One hundred of the 308 patients from 2 of the 63 participating clinical centres (the University Hospital Utrecht and the University Medical Centre Amsterdam), were selected at random for telephone interviews. Nineteen were not interviewed, most of them because they did not have access to a telephone. By a weighted score based on the replies the influence of some baseline variables was explored. The information sheet that patients had received was analysed with the readability tests of Flesh and Fry. RESULTS: Eighty-six percent of all patients were aware of the correct diagnosis. The name and action of the trial drug Ascal (a brand of acetylsalicylic acid) were retained better than those of atenolol. The nature of the disease and therapy were better known than the design of the trial. Of the baseline variables explored only the level of education was significantly related to what patients remembered about the trial. The readability of the information sheet required more education than was intended. CONCLUSION: Although we did not study a random sample the conclusion seems warranted that the level of information was not optimal in this trial. PMID- 1461293 TI - [Intellectual development of patients with phenylketonuria; 15-year national screening in The Netherlands]. AB - OBJECTIVE: To evaluate the intellectual development of patients with phenylketonuria (PKU) or hyperphenylalaninaemia (HPA). DESIGN: Longitudinal follow-up study. SETTING: University Children's Hospitals of Amsterdam, Groningen, Nijmegen, and Rotterdam. METHODS: In September 1974 a nationwide neonatal screening for PKU started in the Netherlands. We obtained data on the intellectual development of 116 patients (101 classical PKU, 15 HPA), all detected and treated in the first 15 years of this screening. The children were tested at 6 ages with different instruments for the assessment of intellectual functions, and the scores were compared with the test norms. Performance and verbal capacities were determined as well as possible sex-related differences. RESULTS: Our data show that the levels of intellectual functioning of PKU and HPA patients do not differ from test norms until the age of 8 yr 6 months. In the older PKU patients there appears to be a trend towards lower IQ scores. We found no sex differences in the mental functioning of PKU patients. CONCLUSION: Continuation of this study is necessary in order to investigate possible negative effects of PKU on cognitive functioning, especially in the older age groups. PMID- 1461294 TI - [Fever caused by neuroleptics]. AB - If fever arises in patients using neuroleptic drugs, it is possible that the fever is an adverse reaction to the drug. Two cases are reported of patients who developed fever to neuroleptic agents. In one patient it probably concerned a reaction to the solvent of the sustained-action preparation of the drug. The other patient developed fever probably as part of the neuroleptic malignant syndrome. PMID- 1461295 TI - [Financing of health research. Expenses and allocation policy]. PMID- 1461296 TI - [Endoprosthesis in the treatment of bile leakage from the cystic duct following laparoscopic cholecystectomy]. PMID- 1461297 TI - [Current possibilities in the treatment of severe stenosis of the major airways]. PMID- 1461298 TI - [Cervical smear and pregnancy: sometimes an unhappy combination]. PMID- 1461299 TI - [Mass screening for cervix carcinoma for the time being not extended to young pregnant or non-pregnant women]. PMID- 1461300 TI - [A normal cervical smear and yet cervical cancer]. PMID- 1461302 TI - [Index of the Nederlands Tijdschrift voor Geneeskunde electronically available]. PMID- 1461301 TI - [Amyloidosis; pathogenesis and therapy]. PMID- 1461303 TI - [14 years of screening for cervix carcinoma in a family practice]. AB - Since 1975 the general practitioners of 'Ons Medies Centrum' in Oss have been inviting women systematically for cervical screening and cervical smears. The attendance and protection rate were evaluated for the period 1975-1989. 85% of the women 35-54 years of age had had a cervical smear within 5 years after they entered the general practice or had not been invited because of a total hysterectomy. After a starting period of a few years the protection rate stabilised at 75%. There was no relation between residential quarter, health insurance, ethnic origin and attendance for the screening. Age was the only factor related to attendance: the attendance rate among older women was lower. PMID- 1461304 TI - [Evaluation of the organization of the mass screening program for cervix cancer in northern Limburg]. AB - The 1990 programme for screening of cervical cancer in North Limburg in the Netherlands was evaluated with a view improving the programme. Information was gathered from women in the screening programme, general practitioners, the health insurance company, the laboratory, and the city councils. With data from literature estimates were made of the effects of the screening in the region. All participants in the screening programme were satisfied with the set-up of the programme. 52% of all women did respond to the invitation for a smear, (in the first 7 months 3620 smears were made). 31% of the women did not need a smear because the uterus had been completely removed or because a smear had been made shortly before. 5% of the women did not receive an invitation. Only 11% of the women who needed a smear did not respond to the invitation, because of lack of time or objections. A so-called 'protection degree' for cervical cancer of 83% was achieved. The degree of protection was the same for different villages, age groups and income levels. The invitation of 12,000 women each year for a smear, leads to an estimate of 185 follow-up tests, detection of 20 women with abnormal results, unnecessary (minor) treatment of 12 women, prevention of two to three major treatments and of one to two deaths per year. Because of the limited positive effects and the relatively large negative effects the authors think that the cervical screening programme is questionable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461305 TI - [Placement in a nursing home does not automatically lead to increased use of drugs]. AB - OBJECTIVE: To determine whether the use of drugs increases during a stay in a nursing home. SETTING: Fifteen nursing homes in Groningen and Haren. DESIGN: Prospective study. METHOD: In 250 persons admitted to a nursing home in the period December 1986-December 1987 the following data were determined: the mean number of different drugs, the total quantity of drugs used expressed in DDDs (Defined Daily Dose), the number of diagnosis and the functioning. RESULTS: The mean number of different drugs used per person per quarter increased significantly (4.5 in the first quarter as against 5.7 in the fourth quarter). The total quantity of drugs expressed in DDDs used per person per quarter, and the mean duration of their being prescribed did not change significantly. An exception were dermatological preparations (0.13 DDDs in the first quarter as against 0.42 DDDs in the fourth quarter), probably in connection with decubitus. CONCLUSION: A stay in a residential home does not necessarily lead to use of larger quantities of drugs (DDDs). However, there are indications that placement may lead to a greater diversity of the drugs used. PMID- 1461306 TI - [Henoch-Schonlein purpura following treatment with streptokinase]. AB - This article presents the clinical history of a man aged 64 who developed Henoch Schonlein purpura after administration of streptokinase for acute myocardial infarction. Because of the increasing use of streptokinase it is assumed that type III hypersensitivity reactions to streptokinase will be seen more frequently. The first symptoms may arise after discharge from the hospital, as symptom-free periods of 3 to 21 days have been reported. PMID- 1461307 TI - [Pregnancy, a good opportunity to extend the domain of cervix screening]. PMID- 1461308 TI - [Safe Motherhood Initiative: the art of the feasible]. PMID- 1461309 TI - [Promoting working during sick leave period through cooperation among insurance physician and treating physician]. PMID- 1461310 TI - [Future perspective for diabetics with nephropathy: not always cause for pessimism]. PMID- 1461311 TI - [Unfavorable prognosis of long-term depression]. PMID- 1461312 TI - [The use of antishock trousers]. PMID- 1461313 TI - [The value of skull and cervical spine radiography in patients following blunt head injury]. AB - In a consecutive series of 100 patients with blunt head trauma the efficacy of routine skull and cervical radiography was studied. Neurocranial and facial skeletal lesions were present in 8 patients, only 1 skull fracture being completely unsuspected clinically. In all 79 patients without cervical signs or symptoms the cervical spine films were within normal limits. Only two of the 21 patients with some form of local cervical spine symptomatology presented with traumatic changes. In 19 patients the cervical spine films did not demonstrate the cervicothoracic junction to satisfaction. Although this study confirms the low yield of routine conventional radiography in patients with blunt head trauma, the authors state that optimal conventional examination of the cervical spine is mandatory in all patients with blunt head trauma and the slightest suspicion of cervical symptoms or complaints and in those patients in whom either clinical examination or the clinical history is not completely satisfactory. The cervicothoracic junction should be adequately visualised. A CT or MRI scan of the brain should be preferred over conventional skull films in those patients in whom examination of the skull is considered indicated. PMID- 1461314 TI - [Is skull radiography indicated in patients with head injuries?]. AB - The value of the radiographic finding of a skull fracture in predicting intracranial haematoma is assessed in this study. Patients with a skull injury can be divided into three risk groups, based on the history and examination findings. The low-risk group includes patients who are asymptomatic or have scalp haematoma, lacerations, headache or dizziness. The moderate-risk group includes patients who have posttraumatic amnesia and/or alcohol intoxication and those who are suspected of having a skull fracture. The patients in the high-risk group have clear symptoms and signs such as depressed level of consciousness or focal neurological signs. The records of 1218 patients were studied. The risk group, the existence of a skull fracture and development of intracranial haematoma were determined. Not a single haematoma was found in the low-risk group. Therefore skull radiography had no significance in this group. In the moderate-risk group two patients had an intracranial haematoma, of whom one patient had a skull fracture. Negative skull radiography therefore did not fully exclude intracranial complications. There were many patients with an intracranial haematoma in the high-risk group, both in the presence and the absence of a skull fracture. CT scanning is the best method of detecting an intracranial haematoma in this group. PMID- 1461315 TI - [Meeting reports in the Nederlands Tijdschrift voor Geneeskunde; value for readers and associations]. AB - OBJECTIVE: To determine the objective of scientific association proceedings in the Nederlands Tijdschrift voor Geneeskunde (NTvG) and whether the objective is met by publication. DESIGN: Interview. SETTING: The editorial office of NTvG MATERIAL AND METHODS: The clinical relevancy of the proceedings published in 1990 and 1991 was determined using selection criteria. 53 (former) secretaries of scientific associations which publish their proceedings in NTvG were interviewed by written questionnaire, and 101 physicians were interviewed by telephone, asking for their opinion on the objective and the use of publishing the proceedings. RESULTS: Of the proceedings (1610 abstracts) published in 1990 and 1991 20% were considered clinically relevant. The opinion of the secretaries of the associations was that the objective of the proceedings is to record medical information and to provide a medical newspaper for the latest reports of the associations, mostly intended for all readers of the NTvG. The secretaries usually correct the abstracts with respect to form and to a lesser extent to informative value. Editorial office selection of the abstracts was not considered desirable, guidelines with regard to writing an abstract of the proceedings were appreciated. More than half of the family physicians read the proceedings, but often considered them too specialised. Half of these thought editorial office selection of the abstracts advisable. About 80% of the specialists read the proceedings, of which the informative value was considered variable. They disapproved of editorial selection. In general physicians read the proceedings very selectively. CONCLUSIONS: The clinical relevancy of the abstracts of the proceedings leaves much to be desired. The objective is to provide a medical record and a newspaper for all readers, but these read the proceedings very selectively. The informative value could be improved. Abstract selection should be in the hands of the associations' secretaries only, but guidelines from the editorial office on writing abstracts are welcomed. PMID- 1461316 TI - [Quality of professional practice: interrelations of the legislative proposal Quality of Health Care Facilities and the Bill Occupations in Individual Health Care]. PMID- 1461317 TI - [Neonatal sepsis caused by Haemophilus influenzae in the first few days of life]. PMID- 1461318 TI - [Minor symptoms in family practice; anal fissure]. PMID- 1461319 TI - [Are long-term results of venous aortocoronary bypass operations really that poor? A prospective 13-year study in 428 patients]. PMID- 1461320 TI - [Severe psychological side effects in children due to use of high-dose deptropine]. PMID- 1461321 TI - Transtracheal oxygen: a step beyond the nasal cannula for long-term oxygen therapy. AB - Transtracheal oxygen represents an important advance in the technology of long term oxygen therapy. As an oxygen conserving technique, it allows increased physical activity with smaller ambulatory and portable units and facilitates the management of patients with refractory hypoxemia outside of the hospital. There is increasing evidence that transtracheal oxygen therapy provides significant physiologic benefits beyond those achieved with the nasal cannula because of tighter control of oxygen therapy and fewer episodes of hypoxemia as a result of uninterrupted 24-hour oxygen therapy. Transtracheal oxygen therapy should be viewed as a program for long-term oxygen administration and not simply as a procedure that involves the insertion of a catheter into the tracheal. Careful patient screening and patient education is important to avoid complications. The program is best administered through regional centers with a team approach to patient care. PMID- 1461322 TI - Need for primary care. AB - OBJECTIVE: This paper is a renewed call for medical schools to address the societal need for more primary care physicians. DATA SOURCES: Numerous studies from the literature are cited as background for this paper. DATA SYNTHESIS: The Author retraces the historical beginnings of the specialty of Family Practice and some of the more recent events which highlight the need for more primary care physicians. CONCLUSIONS: The author concludes that there is a societal need for more primary care physicians and that medical schools should respond to this need. PMID- 1461323 TI - Multidrug regimens in moderate & severe hypertension. AB - We have briefly discussed the antihypertensive drug interactions which result in additive or synergistic actions on lowering of blood pressure when they are administered concomitantly. The choice of antihypertensive agents should be individualized based on the patient's age, race, sex, weight prior therapy, coexisting diseases, underlying diseases, and the pathophysiology of the disease. The goal of antihypertensive treatment extends not only to the control of hypertension per se but also to the reduction of side effect profiles, the treatment of co-existing diseases and optimizing quality of life. PMID- 1461324 TI - Natural history of at-risk Lynch syndrome family members with respect to adenomas. AB - Our goal is to determine colon cancer surveillance strategy in patients at risk for Lynch's syndrome. Asymptomatic persons at 50% risk of having Lynch syndrome (age 25-70 years) were enrolled in colonoscopic screening. Those without adenomas were asked to return in one year. Those with adenomas were asked to return in six months because of concern for rapid malignant degeneration. RESULTS: Twenty-five males and thirty females participated. On initial exam, eight of fifty-five patients (14.5%) had adenomas. Logistic regression showed a significant effect of age on the probability of finding adenomas at initial examination (p < 0.02). Followup was available in 27 patients (mean 35.5 months). Kaplan-Meier estimation of time to finding new or previously missed adenomas was 58 months for patients clear on first colonoscopy and 16 months for patients who had adenomas on first exam (p < 0.01). One adenocarcinoma has been found arising in a tubulovillous adenoma. CONCLUSION: The short-term risk of colorectal cancer in Lynch syndrome relatives without adenomas is low, as is the risk in those who have had all visualized adenomas removed. PMID- 1461325 TI - Merging the departments of psychiatry of a private and state university: the Nebraska experience. AB - Medical colleges throughout the nation are being pressured to decrease the costs of medical education. In some of our smaller cities, the duplication of faculty expertise and costly technological resources at distinct but neighboring campuses has led to training costs far beyond what can be comfortably supported by either the institutions or their students. While the trend toward collaboration or mergers between identical medical departments on adjacent campuses is gaining ground, the methods required to achieve success in these ventures remain relatively uncharted. This paper provides an overview of the creation of successful merger between the departments of Psychiatry of Creighton University School of Medicine and the University of Nebraska College of Medicine. The development of the merger from conception to completion, along with the lessons learned along the way, are offered in the hope that other medical departments may benefit. PMID- 1461326 TI - Management of breech presentation at term. PMID- 1461327 TI - [Introduction: vasospasm after a ruptured aneurysm]. PMID- 1461328 TI - [Cerebral vasospasm. Experimental study]. AB - We have studied chronic vasospasm (V.S.) on a primate model (Cynomolgus monkey). The conclusion of several studies are: V.S. is related to the presence of adherent clots along cerebral arteries and when severe may lead to cerebral infarction. Clots removal within 48 h. following subarachnoid hemorrhage reduces V.S. intensity. Free radicals and iron dependent lipidic peroxidation have been involved in cerebral ischemia development. A new aminosteroid (U 74006 F) can act as a free radical phagocyte and antagonize iron dependent lipid oxidation. Histological V.S. changes are less important after S.A.H. with 74006F treatment. Oxyhemoglobin high concentration from red blood cells (R.B.C.) hemolysis has been reported to be responsible for V.S. Therefore induction of R.B.C. release from the clots before hemolysis occurs could prevent from high concentration of oxyhemoglobin. Plasminogen activator can prevent V.S. when used during 72 h. following subarachnoid hemorrhage. PMID- 1461329 TI - [Effect of nimodipine on vasospasm of cortical arteries. Experimental study]. AB - The efficacy of the calcium channel blocker Nimodipine (N) in prevention and treatment of chronic cerebral vasospasm (V.S.) after subarachnoid haemorrhage (S.A.H.) was tested in a blind randomized experimental study. Twenty seven dogs (French Grande Venerie) weighing between 40 to 50 kg, were randomly assigned in three groups. Under general anesthesia, each animal underwent baseline angiography, followed by right frontotemporal craniectomy. A retractor was placed under the temporal lobe and the arachnoid membrane over the internal carotid artery was dissected. 10 ml of autologous arterial blood was placed around the internal carotid artery, and 5 ml of arterial blood was injected into the cisterna magna. Group I was placebo group: ten randomly pre selected animals received a placebo. Group II was preventive group: seven animals received N (5 mg/kg) per os each day, from D0. Group III was curative group: ten animals received N (5 mg/kg) per os each day, from D2. At Day 2 and Day 5, all animals underwent a control angiography. The basilar artery, the internal carotid artery were measured. The craniectomy was reopened and the cortical arteries were measured with a calibrated optical micrometer. Intergroup comparisons at Day 0, Day 2 and Day 5, were made by analysis of variance. The level of significance was n < 0.05. V.S. was defined as a reduction in vessel caliber of 10% or greater, compared to baseline value. In the placebo group (Group 1), V.S. of the basilar and cortical arteries was present in all cases, from D2 to D5.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461330 TI - [Diagnosis of vasospasm: comparison between arteriography and transcranial Doppler. A series of 112 comparative tests]. AB - 56 consecutive patients with ruptured aneurysm (An) were studied. The An localisation were: anterior communicating artery (ACoA) 26 cases, internal carotid artery (I.C.A.) 13 cases, Middle cerebral artery (M.C.A.) 11 cases, Pericallosal artery (P.C.A.) 4 cases, anterior cerebral artery (A.C.A.) 2 cases. Nimodipine infusion was started as soon as the diagnostic was established. Transcranial Doppler (T.C.D.) and angiography (A degrees) were performed at the arrival and 10 to 12 days after surgery. Surgery was performed in the 72 first hours after S.A.H. in 79% of the cases. 112 comparisons A degrees-T.C.D. were available. An A degrees vasospasm (V.S.) was assessed if the reduction of calibre was 25% or more, on T.C.D. V.S. was assessed if mean cerebral flow (M.C.F.) was equal to or more than 130 cm/sec. There were 15 cases of A degrees V.S. in 14 patients: 2 cases before surgery, 1 case before and after surgery in the same patient and 11 cases after surgery. D.T.C. exhibited 11 cases of V.S. at the level of M.C.A.; there were 11 true positive, 0 false positive, 97 true negative and 4 false negative. The diagnosis of V.S. was always correct with T.C.D. when A degrees V.S. was present at the level of M.C.A., it was not made when A degrees V.S. was restricted to the initial part of A.C.A. (A1) uni or bilaterally: 3/6 cases of ACoA. An rupture or to I.C.A.: 1/4 case of I.C.A. An. rupture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461331 TI - [Cerebral blood flow in the determination of vasospasm and surgical decision]. AB - The interest of C.B.F. studies performed on patients with subarachnoid haemorrhage is discussed on the basis of the literature and of our experience of 142 cases. C.B.F. results in basic condition are influenced by many factors which make its use very limited and especially during the first days after haemorrhage (J0-J3). However, the analysis of the evolution of C.B.F. values in the same patient and moreover the C.B.F. reactivity to acetazolamide are good indicators of the occurrence of a vasospasm; progressive drop of the C.B.F. or poor reactivity are generally observed before clinical signs of vasospasm. Our policy is therefore to decide the date of surgery according to C.B.F. values but only for patients planned for delayed surgery (after the 3rd day). PMID- 1461332 TI - [Contribution of 99m Tc-HMPAO single-photon emission-computed tomography to the perioperative evaluation of subarachnoid hemorrhage caused by ruptured aneurysms]. AB - Twenty one cases of proven subarachnoid hemorrhage (S.A.H.) have been analysed in a protocol especially including transcranial doppler (T.C.D.) and 88mTc H.M.P.A.O. single photon emission tomography (H.M.P.A.O.-S.P.E.C.T.). Seventeen patients were intraoperatively studied. All data were compared with clinical grading, computerized tomography (C.T.) and angiography. S.P.E.C.T. is a quite recent method of measuring and three-dimensional imaging of brain perfusion. It provides important information for the diagnosis of ischemic syndromes in S.A.H. Sixty-two S.P.E.C.T.-scans were performed in twenty one patients. Fifty-eight were abnormal and showed significant abnormalities of brain perfusion varying in extent and severity. In this preliminary study, we set out to validate the clinical use of H.M.P.A.O.-S.P.E.C.T. for the diagnosis of "vapospasm" comparing S.P.E.C.T. data with classical criteria. We propose a classification which allowed us to quantify the ischemic risk in an attempt to adapt the global therapeutic management to hemodynamic data. This method appears to be very sensitive and reliable in this field. It will introduce, if these first results are confirmed, important criteria for the evaluation of patients presenting with S.A.H. as far as prognosis and treatment are concerned, especially in regard to timing of surgery and institution of medical hemodynamic therapy. PMID- 1461333 TI - [Vasospasm, early surgery and nimodipine. A series of 120 consecutive cases of surgically treated ruptured aneurysm]. AB - A total of 120 consecutive ruptured aneurysms (An) were managed according to a radio clinical investigation protocol. Preoperative evaluation included clinical grading (Hunt & Hess classification) (3 patients were Gr. I, 62 Gr. II, 27 Gr. III, 13 Gr. IV, 15 Gr. V) angiography (A degree) and C.T.Scan grading. Nimodipine infusion was started before surgery (1 mg/Kg/h). Surgery was performed from Day 0 to Day 3--Control A degrees and C.T.Scan were performed 10 to 12 days after surgery. Post operative C.T.Scan hypodensities were evaluated according to preoperative C.T.scan anc control A degrees. The outcome was evaluated according to the Glasgow Outcome Score (G.O.S.) and the causes of sequelae and decreases were listed according to vasospasm (V.S.), initial hemorrhage and post operative thrombosis (T.H.R.). The outcome was good or excellent in 95.4% of 65 Gr. I.II cases, in 85.9% of 92 Gr. I.II.III cases. Among the causes of disability or death only one case of diffuse severe V.S. was noted; besides that and according to our experience V.S. incidence was lower in this series (25%) than in our previous experience. It is stated that nowadays with Nimodipine treatment and early surgery V.S. is no more a problem. PMID- 1461335 TI - [Cerebral vasospasm: conclusion]. PMID- 1461334 TI - [Transluminal angioplasty in the treatment of vasospasm. Value of transcranial Doppler in the diagnosis and follow-up]. AB - Vasospasm (V.S.) transluminal angiographic treatment (T.L.A.) is recommended in case of symptomatic V.S. before or after surgery. V.S. diagnosis and follow up after T.L.A. rely on clinical and transcranial doppler (T.C.D.) data. Before T.L.A. angiography (A degrees) demonstrates V.S. degree and location. T.L.A. technic is described. The authors report 14 cases of T.L.A. (7 before and 7 after surgery). Before surgery in 4 cases patients exhibited ischemic symptoms from V.S.: 2 died (one from reanimation problems the other from a new hemorrhage). After surgery of 7 patients one died from artery rupture, one from extra neurologic complication. T.C.D. capacity to follow up V.S. is emphasized. As soon as T.L.A. is performed the mean cerebral blood flow (C.B.F.) decreases (< 100 cm/s) and does not increase anymore. At the level of non dilated arterial segments V.S. may increase after T.L.A.: it is then recommended to dilate all the spastic arteries, as far as it is possible. After T.L.A. C.B.F. may decrease in arteries far from the dilated ones probably because arterial supplies are no more necessary. PMID- 1461336 TI - [Juxtabulbar neurinoma of the spinal accessory nerve]. AB - A 27-year-old woman presented with right spinal accessory juxtabulbar schwannoma, associated with hydrocephalus. The only specific clinical symptom was long standing weakness of the right trapezius. C.T. scan evoked a cerebellar tumor, whilst the jugular foramen appeared normal. Vertebral angiography was not decisive. M.R.I. suggested an extra-axial tumor. Post-operative evolution was entirely favourable. Schwannomas of the 9th, 10th and 11th cranial nerves are generally located at the level of the jugular foramen but can also be observed along the extracranial path of these nerves. An intracranial paramedial, or so called "intracisternal" localization is rare and is best diagnosed by magnetic resonance imaging. PMID- 1461337 TI - [Deep sylvian meningioma. Apropos of a case. Review of the literature]. AB - One case of deep sylvian meningioma without dural attachment is reported. Ten cases have been described in the literature leading to discussion of histological origin, clinical characteristics, neuroradiological data and surgical results. PMID- 1461339 TI - [Postoperative dural tightness. Value of suturing of the pericranium in surgery of the posterior cranial fossa]. AB - It is difficult to have the dura-mater of the posterior fossa tightly closed, with no excessive traction especially when it was necessary to coagulate some vessels. The use of a pericranial graft taken in the interparietal area on up of the occipital craniotomy permits a tight closure, preventing pseudomeningocele via diffusion of CSF, and without tension gaining space which permits a better tolerance of the post-operative cerebellar oedema. PMID- 1461338 TI - [Neurinoma of the oculomotor nerves. Apropos of 2 cases]. AB - The authors report two cases of neurinomas of the oculomotor nerves: one neurinoma of the oculomotor nerve and one of the abducens nerve. The study of 30 cases in the previous literature points out the major striking features of these tumors. Both headaches and oculo-motor palsies are the most regular clinical features. They are not typically suggestive. Therefore the diagnosis is difficult among all the tumors of cavernous sinus and surrounding structures. C.T. scan and M.R.I. with the clinical history should readily allow pre-operative diagnosis. These data are insufficient to distinguish the affected nerve. The surgical treatment is not always complete due to the tumor infiltration into the cavernous sinus. PMID- 1461340 TI - Special issue: Is beta-amyloid neurotoxic? PMID- 1461341 TI - In vivo neurotoxicity of beta-amyloid [beta(1-40)] and the beta(25-35) fragment. AB - We examined the histological changes produced by injections of beta-amyloid [beta(1-40)], and control peptides in rat and monkey cerebral cortex. beta(25-35) injections were also studied in rat cortex. Standard immunoperoxidase procedures were used to detect the distribution of tau, MAP2, beta(1-40) and ALZ 50 immunoreactivity. All injections produced localized necrosis at the injection site surrounded by a zone of neuronal loss and gliosis. In rat cortex, lesions produced by solubilized beta(1-40) and beta(25-35) in water were generally larger than those produced by control peptides. Tau and ALZ 50 antibodies labeled neurites and diffusely positive perikarya around beta(1-40) injections, whereas MAP2 staining was reduced, paralleling the distribution of neuronal loss and gliosis. In aged primate cortex, beta(1-40) lesion size was dose dependent. Hyalinized, ALZ 50 positive neurons, and abnormal neurites were prominent around the injection site. Although beta-amyloid is acutely neurotoxic in both rat and monkey cerebral cortex, neuronal degeneration in the primate more closely resembles that found in AD. PMID- 1461342 TI - Effect of beta amyloid peptides on neurons in hippocampal slice cultures. AB - Several investigators have described the neurotrophic and neurotoxic effects of beta amyloid peptide fragments on dissociated hippocampal neurons in culture. In these prior studies, the peptides were added to dissociated cultures between day 0 and day 4 in vitro, before hippocampal neurons are fully mature. We have analyzed the neurotrophic and neurotoxic effects of beta amyloid fragments beta 1 28, beta 25-35 and beta 1-40 on hippocampal slice cultures, whose physiology and morphology resembles the intact hippocampus. Addition of beta 1-28 or beta 25-35 to the growth medium did not produce significant changes in dendritic length or number of branches. Nerve growth factor, previously reported to enhance the neurotoxic effects of beta 1-40 on dissociated hippocampal neurons in culture, did not significantly enhance the neurotrophic effects of beta 1-28. To achieve high local concentrations of peptides and to avoid potential access problems in the cultures, we injected beta 1-28, beta 25-35, and beta 1-40 directly into the cultures. Amyloid-mediated neurotoxicity was not observed for beta 1-28 or beta 25-35, but beta 1-40 appeared to produce neurodegeneration around the site of injection. PMID- 1461343 TI - The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected beta-amyloid in the rat brain. AB - The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta amyloid protein (beta AP1-40) was studied in rats. A synthetic peptide with the reverse sequence (beta AP40-1) or the vehicle alone were injected in the contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that beta AP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. beta AP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that beta AP1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease. PMID- 1461344 TI - Lack of Alzheimer pathology after beta-amyloid protein injections in rat brain. AB - In order to establish a direct relationship between beta-amyloid protein (beta AP) and in vivo neurotoxicity, we made intraparenchymal injections and Alzet pump infusions of beta AP into the hippocampus and cortex of adult rats. We tested a number of synthetic beta AP peptides (beta AP 1-40, 1-38, and 25-35) and peptide controls (scrambled and reversed 1-40, and scrambled and reversed 25-35) over a wide range of concentrations and in a variety of vehicles. The rats were sacrificed from 2-35 days following the implant, and the brains examined by standard immunohistochemical and histological methods used to evaluate the pathologies associated with Alzheimer's disease. We report the lack of Alzheimer related pathology and no significant morphological differences between the beta AP peptide and the peptide and vehicle control injections. These observations indicate that the simple intraparenchymal injection of beta AP in the rat brain is not an appropriate model of Alzheimer-related neurotoxicity. PMID- 1461345 TI - Failure of beta-amyloid protein fragment 25-35 to cause hippocampal damage in the rat. AB - Considerable excitement has been generated as of late over reports that fragments of the amyloid precursor protein can be neurotoxic both in vivo and in vitro. In this brief report we study the neurotoxicity of the fragment corresponding to amino acids 25-35 of the beta-amyloid protein in the hippocampus in vivo. Under the conditions studied, we do not observe any evidence of consistent, dose related damage above that seen with vehicle alone. PMID- 1461346 TI - Implants containing beta-amyloid protein are not neurotoxic to young and old rat brain. AB - Because the cellular effects of beta-amyloid protein (beta-AP) are currently unclear, we evaluated the in vivo effects of beta-AP implants in a lipid matrix to prolong tissue exposure in the brains of rats. Young 3-month-old rats and aged 18-month-old rats received implants of beta-AP prepared in a cocoa butter matrix in the dorsal hippocampus and corpus striatum on one side of the brain and implants of either prolactin or scrambled beta-AP peptide in cocoa butter on the contralateral side. The old rats also received implants of beta-AP embedded in a cholesterol matrix or cholesterol alone in the frontal cortex. The young rats were sacrificed 3-4 days after implantation, while the old rats were sacrificed 6 8 weeks after implantation. Lesion size on the beta-AP implanted side did not differ significantly from lesion size observed with control peptides. Bielschowsky silver staining revealed few argyrophilic neurites and axonal spheroids associated with either beta-AP or control implants. Alz 50 and ubiquitin immunoreactivity were not observed. None of the implant sites demonstrated cytopathology characteristic of Alzheimer's disease. The results of this study indicate that beta-AP implantation into the brains of rats produced no consistent effect beyond that seen with control peptide implants. PMID- 1461347 TI - beta-Amyloid neurotoxicity: a discussion of in vitro findings. AB - Significant advances in Alzheimer's disease (AD) research require definitive, reproducible findings from all employed paradigms. Recently, the existing in vitro data addressing the possible contribution of beta-amyloid protein to AD neuropathology have been the subject of controversy. We summarize and interpret existing data and discuss relevant methodological issues. We suggest that in vitro data support the conclusion that beta-amyloid peptides decrease the viability of cultured neurons and that this effect can be enhanced by subsequent insults. PMID- 1461348 TI - Solvent effects on beta protein toxicity in vivo. AB - Human beta (1-40) and rat beta (1-42) were dissolved in three different solvents and stereotaxically injected into rat hippocampus with the contralateral side injected with control reverse sequence peptide or vehicle alone. Results at 1 week showed gross toxicity of the 35% acetonitrile solvent which was markedly enhanced by 3 nmol of beta protein but not by reverse sequence peptide. Beta peptide in water also appeared more toxic than reverse sequence, but the results were less clear cut. In contrast, 3 nmol of beta peptide in a cyclodextrin/PBS solution produced no marked short-term toxic effects. Peripheral injection of substance P failed to prevent toxicity. We conclude that solvent effects play a major role in acute beta protein neurotoxicity. PMID- 1461349 TI - The nature and metabolism of potentially amyloidogenic carboxyl-terminal fragments of the Alzheimer beta/A4-amyloid precursor protein: some technical notes. AB - The proteolytic processing and secretion of APP are regulated by protein phosphorylation, especially via protein kinase C and protein phosphatases 1 and/or 2A. Our studies of these regulatory mechanisms have led us to perform extensive experimentation on the metabolism of APP carboxyl-terminal fragments, using as our system either untransfected, undifferentiated rat pheochromocytoma (PC12) cells or APP-baculovirus infected Sf9 cells. We have not assayed APP fragments for biological activity in either system. However, we have made potentially relevant observations regarding APP carboxyl-terminal fragment trafficking. In this note, we review our published and unpublished data in relation to published reports from other laboratories using related systems. PMID- 1461350 TI - Methodological variables in the assessment of beta amyloid neurotoxicity. AB - Cell culture systems for evaluating the biological effects of the beta-amyloid protein are potentially important tools in the study of the pathogenesis of Alzheimer's disease. In this report, methodological considerations in the assessment of beta-amyloid neurotoxicity are discussed. Chronic incubation of beta 1-40 in primary human cortical cultures results in progressive neuronal degeneration. The neurodegenerative process occurs in association with localized deposition of beta-amyloid on the neuronal soma ultimately resulting in the formation of compact beta-amyloid deposits. A beta 1-40 preparation from another laboratory was tested that did not form neuronal beta-amyloid deposits and was not neurotoxic. Thus, the conformational state of the beta 1-40 peptide leading to the formation of neuronal amyloid deposits is an important determinant of neurotoxicity. Variables in peptide preparation that influence this property may account for variation in neurotoxic potency. PMID- 1461351 TI - Alz 50 as a reagent to assess animal models of Alzheimer's disease. AB - As will be apparent from a reading of the papers included in this issue, one reagent that has been used extensively in assessing the effects of the beta/A4 peptide on rodent neurons is the monoclonal antibody Alz 50. A variety of model systems have been employed, in which beta/A4 is delivered to neurons both in vitro, and in several different ways, in vivo. While Alz 50 can be a useful reagent in these studies, there are limitations to the utility of this antibody, and it is important to recognize that appropriate controls must be performed to establish the specificity of observed immunoreactivity. PMID- 1461352 TI - Commentary and perspective on studies of beta amyloid neurotoxicity. PMID- 1461353 TI - beta-Amyloid precursor protein and Alzheimer's disease: the peptide plot thickens. PMID- 1461354 TI - Toxicity of synthetic A beta peptides and modeling of Alzheimer's disease. PMID- 1461355 TI - The dynamic properties of neuronal chromatin are modulated by triiodothyronine. AB - The effect of triiodothyronine (T3) on the rate of synthesis of nuclear proteins was studied during terminal differentiation of rat cortical neurons cultured in a serum-free medium. To this aim total and acid soluble nuclear proteins were analyzed by different electrophoretic techniques. Our results show that: 1) during maturation in vitro, neuronal nuclei undergo a dramatic change in the rate at which different classes of histones and high mobility group (HMG) proteins are synthesized; the synthetic activity, measured as incorporation of radioactive precursors into nuclear proteins, slows indeed down with age: especially evident is the decrease in core histones synthesis; at day 15, on the other hand, HMG 14 and 17 and ubiquitinated H2A (A24) are synthesized at a high rate, especially in T3-treated neurons; 2) neurons treated with T3 show, at any age tested, a higher level of lysine incorporation into nuclear proteins; 3) even if during the first days of culture neurons synthesize core histones more actively in the presence of T3, there is no accumulation of these proteins at later stages, as compared with untreated cells. Possible implications of these data and relationship with the chromatin rearrangement which accompanies neuronal terminal differentiation are discussed. PMID- 1461356 TI - Autoradiography of muscarinic cholinergic receptors in cortical and subcortical brain regions of C57BL/6 and DBA/2 mice. AB - Mice of the inbred strains C57BL/6 and DBA/2 show strain-dependent behavioural differences which have been correlated with variations in brain cholinergic systems. In the present study, the density of muscarinic cholinergic receptors in both strains of mice was determined by autoradiographic methods using [3H]quinuclidinyl benzilate (QNB) and [3H]pirenzepine as ligands. C57BL/6 mice showed a significantly lower [3H]QNB binding level in the frontal cortex by one third as compared to DBA/2 mice. In the striatum and the cholinergic pontomesencephalic nucleus laterodorsalis tegmenti the [3H]QNB binding was lower in C57BL/6 by 28% and 31%, respectively. The [3H]pirenzepine binding level was found to be significantly higher in C57BL/6 temporal cortex (by 22%). These results are discussed in relation to interstrain differences in cholinergic cell density and in the activity of cholinergic enzymes. PMID- 1461358 TI - Effect of liposomes on lipid peroxidation and total phospholipids in rabbit ischemic spinal cord model. AB - The effect of spinal cord ischemia (induced by abdominal aorta ligation for 20 minutes) on lipid peroxidation and TPL composition was investigated and discussed in our previous articles. It is known, that partially reduced species of oxygen can be formed under aerobic conditions. For that reason, the effect of ligation release for 60 minutes was observed in experimental animals treated with the selected liposomes. Administration of CP, (CP+SA) and (CP+Chol) liposomes applied 30 minutes before 20 minutes ischemia revealed an ameliorating effect on in vivo and in vitro Fe-dependent peroxidation manifested by TBA-RS accumulation. Combined use of (CP+SA) liposomes with lipophylic form of stobadine (DP 1031) was not more effective. Application of CP liposomes directly before the ligation release slightly increased the antiradical capacity in spinal cord homogenates comparing with not-treated animals. Accumulation of TBA-RS was accompanied by TPL degradation during recirculation period but values of TPL after liposomal treatment were unaffected. PMID- 1461357 TI - Ethacrynic acid and furosemide alter Cl, K, and Na distribution between blood, choroid plexus, CSF, and brain. AB - Can loop diuretics like ethacrynic acid and furosemide, when administered intravenously, significantly alter ion transport and fluid dynamics in CNS? To shed light on this unresolved issue, we tested the ability of these agents to effect redistribution of Na, K and Cl in adult rat brain. Cl penetration into various CNS regions was assessed as the volume of distribution, i.e., uptake, of 36Cl from blood. Ethacrynic acid and furosemide (50 mg/kg IV) reduced by 20-30% the rate of permeation of 36Cl across the blood-CSF barrier, and they elevated [K] and [Cl] in choroid plexus (CP) by 15-25%. The loop diuretic-induced buildup of K and Cl in CP (lateral and 4th ventricle) was likely a reflection of decreased movement of these ions across the apical membrane into CSF. 36Cl activity in parietal cortex and pons-medulla decreased in treatment with furosemide and ethacrynic acid, due to slowing of Cl transport across blood-brain and/or blood-CSF barriers. Our inhibitory findings in intact rats are consistent with those from previous in vitro experiments demonstrating diminution by loop diuretics of Na, K and Cl transport across isolated CP membranes. PMID- 1461359 TI - Long term regulation of nucleoside transport by thyroid hormone (T3) in cultured chromaffin cells. AB - The adenosine transport in cultured chromaffin cells was increased by the presence of triiodo-L-thyronine (T3) throughout the prolonged period studied. The Vmax values of this transport obtained in absence and presence of 1 microM T3 were 36.21 +/- 2.1 and 44.17 +/- 3.5 (means +/- SD) pmol/10(6) cells/min respectively for 26 hours incubation-time with the hormone. The Km values were not significantly modified. The number of adenosine transporters in cultured chromaffin cells, measured by [3H]nitrobenzylthioinosine (NBTI) binding, was increased by 1 microM T3 for 26 hours incubation-time. The values of binding sites per cell were 33,500 +/- 3,000 and 40,153 +/- 3,700 in absence and presence of T3 respectively, without changing the Kd constant. When the transport studies were carried out in presence of cycloheximide, an inhibitor of protein synthesis, the adenosine transport capacity decreased with a half-life values of 23.9 +/- 2.8 and 24.3 +/- 2.1 hours both in the presence or absence of T3 respectively. When cells were incubated in the presence of both T3 and cycloheximide, not only the activatory effect of T3 was completely abolished but also adenosine transport was decreased to the same extent as with cycloheximide alone. These results indicated that T3 activation of adenosine transport in chromaffin cells required the protein-synthesizing mechanism. PMID- 1461360 TI - Norepinephrine, dopamine, and 5-HT release from perfused hypothalamus of the rat during feeding induced by neuropeptide Y. AB - In the unrestrained rat, the hyperphagic-like ingestion of food evoked by the sustained elevation of neuropeptide-Y (NPY) in the hypothalamus was correlated with the release and turnover of monoaminergic transmitters in this structure. A single guide tube was implanted stereotaxically in the perifornical region of the hypothalamus for localized push-pull perfusion of an artificial CSF vehicle or NPY1-36 in a concentration of 10, 50, or 100 ng/1.0 microliters. After the rat was fully satiated, a site reactive to NPY was perfused repeatedly at a rate of 20 microliters/min for 6.0 min with an interval of 6.0-12 min elapsing between each perfusion. Samples of perfusate were analyzed by HPLC with coulometric detection for DA, HVA, DOPAC, NE, MHPG, 5-HT, and 5-HIAA. Although control perfusions were without effect on feeding or monoamine activity, NPY evoked mean cumulative intakes of food of 14 +/- 2.4, 25.6 +/- 3.0 and 26.5 +/- 3.2 g in response to 10, 50, or 100 ng/microliter concentrations of NPY, respectively, over the 4.0-5.0 hr test interval. HPLC analyses showed that during feeding the release of both NE and DA was enhanced significantly. The turnover of both catecholamines likewise increased significantly as reflected by the elevated levels of MHPG, DOPAC and HVA. However, neither the basal efflux of 5-HT nor its turnover, as reflected by the output of 5-HIAA, was affected during feeding induced by NPY perfused in the hypothalamus. These results suggest that a sustained elevation of NPY in the hypothalamus causes a perturbation in the basal activity of NE and DA which are both implicated in the neuronal mechanism regulating normal eating behavior. Thus, these catecholamine neurotransmitters are envisaged to comprise an intermediary step in the functional role played by NPY in the hypothalamus in integrating the control of energy metabolism and caloric intake. PMID- 1461362 TI - Mitochondrial factors involved in Parkinson's disease by MPTP toxicity in Macaca fascicularis and drug effect. AB - The maximal rates (Vmax) of some mitochondrial enzyme activities related to energy transduction (citrate synthase, succinate dehydrogenase, malate dehydrogenase, NADH-cytochrome c reductase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate- and glutamate oxaloacetate- transaminases) were evaluated in non-synaptic ("free") and intrasynaptic "light" and "heavy" mitochondria from hippocampus of Macaca fascicularis (Cynomolgus monkey). The different mitochondrial populations were isolated from the hippocampus of monkeys treated p.o. with dihydroergocryptine at a dose of 12 mg/kg/day before and during the induction of a Parkinson's-like syndrome by MPTP administration (i.v., 0.3 mg/kg/day for 5 days). The MPTP administration modified the activity of some enzymes related to the metabolism of glutamate and the activity of succinate dehydrogenase on selected types of mitochondria. Pharmacological treatment by dihydroergocryptine promoted return to the steady-state levels of most enzymes, demonstrating a protective effect on these biochemical parameters. PMID- 1461361 TI - Regional effects of neurotensin on the electrically stimulated release of [3H]dopamine and [14C]acetylcholine in the rat nucleus accumbens. AB - This study has shown that neurotensin (NT) increases the electrically stimulated release of [3H]DA to a similar extent in all but the extreme caudolateral area of the rat nucleus accumbens and appears to modulate DA release equally in the medial and lateral zones of this brain area. The simultaneous release of ACh was not significantly affected by NT. PMID- 1461363 TI - Soluble enkephalin-degrading enzymes released by lymphomic and erythroleukaemic cell lines. AB - The possible existence of soluble proteolytic enzymes released by cells of lymphomic (U937 and 1301) and erythroleukaemic (K562) lines was studied measuring the hydrolysis of 3H-leucine enkephalin in the presence of cell-free supernatants obtained from these lines. Results indicate that leu-enkephalin is rapidly degraded in the presence of these supernatants, and that enkephalin disappearance is paralleled by the formation of peptides that can be interpreted as its hydrolysis fragments. To characterize the factors involved in leu-enkephalin degradation, cell supernatants were analyzed by ion exchange and by steric exclusion chromatography. Data obtained indicate the presence of three groups of proteins active in leu-enkephalin degradation: aminopeptidases, dypeptidylaminopeptidases and dypeptidylcarboxypeptidases. In all three lines, these enzymes are represented by a considerable number of distinct activities. The sizable number of soluble enzymes identified and the significant total activity observed suggest a possible role in the regulatory degradation of informational peptides, as proposed by several groups for the membrane-bound proteolytic enzymes of immunocompetent cells. PMID- 1461365 TI - Germanium-68 as a possible marker for silicon transport in rat brain. AB - Silicon (Si) is an essential trace element normally present in brain and cerebrospinal fluid, although the mechanism by which it enters and distributes in brain is largely unknown. Due to the short radioactive half-life of 31Si (156 min) we have investigated the use of 68Germanium (68-Ge, half-life 282 days) as a possible marker for Si transport in rat brain over longer periods than are possible with 31Si. Adult male anaesthetised rats were given a bolus of 68Ge I.V. and arterial blood samples taken during experiments that lasted between 5 min and 3 days. At termination, the brain was removed and analysed for radioactivity as were the plasma samples. Data were analyzed by Graphical Analysis which showed that the blood-brain barrier permeability to 68Ge (Kin approximately 10(-4) ml/min/g) is similar to that for many non protein-bound electrolytes in plasma and that 68Ge fluxes across cerebral capillaries are bidirectional. The autoradiographic distribution of 68Ge in brain was homogenous. Our results are in agreement with those of previous studies using 31Si or 68Ge, which suggest 68Ge may be a useful marker for Si when investigating the role of this element in conditions such as neurodegenerative diseases. PMID- 1461366 TI - Enhanced GABA release in cerebral cortical slices derived from rats with thioacetamide-induced hepatic encephalopathy. AB - The release of newly loaded [3H]GABA was studied in slices of different brain regions derived from rats in which acute hepatic encephalopathy (HE) was induced with a hepatotoxin thioacetamide. HE increased both spontaneous and high (50 mM) ammonium chloride-evoked GABA release in cerebral cortical slices by 38% and 50%, respectively. No effects of HE were noted in cerebellar or striatal slices. An increased release of GABA in the cerebral cortex may contribute to the endogenous benzodiazepine-mediated enhancement of GABAergic tone, which is thought to be partly responsible for the pathophysiological mechanism of HE. PMID- 1461367 TI - Velocity of Ellman's reaction and its implication for kinetic studies in the millisecond time range. AB - A detailed study of the velocity of the reaction between Ellman's reagent and thiocholine was undertaken, in order to test the possibilities of this reaction as a detection method for the earlier stages of cholinesterases reactions. Experiments were carried out on a stopped-flow apparatus with a built-in spectrophotometer. The obtained experimental data were analyzed by fitting the data to theoretical kinetic equations derived for the reaction. In this way, a complete kinetic characterization of the reaction was obtained. An important practical result derived from our investigations is the finding that, under most experimental conditions, the Ellman's reaction is more than sufficiently rapid as a detection method. However, in the case of reactions in the time scale of 200 milliseconds or less, this being 5 times the half life of Ellman's reaction at standard conditions, one has to consider the interference of this reaction with the enzyme reaction itself. PMID- 1461368 TI - Structure of hypothalamic coronaro-constrictory peptide factors. AB - The following peptide structure in 3 of 5 coronaro-constrictory peptide factors isolated from bovine hypothalamus was determined by amino acid analysis and Edman degradation: 1) (P1)--Val-Val-Tyr-Pro-Trp; 2) (P2)--Val-Val-Tyr-Pro-Trp-Thr; 3) (P3)--Leu-Val-Val-Tyr-Pro-Trp-Thr. A computer search for these amino acid sequences revealed that these peptides represent fragments 33-37; 33-38; 32-38 of the beta-chain of bovine hemoglobin. Solid phase peptide synthesis of 2 peptides (P2 and P3) was carried out. It was established that synthetic peptides had the properties of coronaro-constrictory peptides. The possibility of the formation of hypothalamic coronaro-constrictory peptides in vivo is discussed. PMID- 1461369 TI - Evaluation of the mechanisms by which gamma-amino-butyric acid in association with phosphatidylserine exerts an antiepileptic effect in the rat. AB - The i.p. injection in rats of GABA (740 mg/Kg) after sonication with an equal amount of phosphatidylserine (PS) has an antiepileptic effect. The injection of plain GABA has no such an effect. Blood, brain and synaptosomal accumulation of exogenous labeled GABA under the two circumstances are evaluated. In the case of GABA/PS injection there is a higher passage of the exogenous labeled neurotransmitter into the blood and brain nerve endings (synaptosomes). A higher synaptosomal accumulation of the exogenous labeled neurotransmitter is found even when GABA and PS are injected separately. Since these accumulation increases occur at a time when there is the antiepileptic effect, they seem relevant to it. Our interpretation of the chain of the events resulting in the antiepileptic action is that the phospholipid facilitates from the beginning the first passage of the exogenous neurotransmitter form the peritoneum to the blood. Then a higher passage to the brain tissue and eventually to the GABA-ergic nerve endings ensues. The brisker accumulation of the exogenous neurotransmitter in the nerve endings could be at the basis of a more efficient GABA-ergic inhibitory control in the brain. PMID- 1461364 TI - Neuronal cell cultures: a tool for investigations in developmental neurobiology. AB - The aim of this review is to describe environmental requirements for survival of neuronal cells in culture, and secondly to survey the complex interplay between hormones, neurotrophic factors, transport- and extracellular matrix- proteins, which characterize the developmental program of differentiating neurons. An overall reconsideration of the literature in this vast field is above the limits of the present paper; since progress and refinement in the techniques of neuronal cell cultures have paralleled the advancement in Developmental Neurobiology, we will run instead through the main steps which form the conceptual framework of neuronal cell cultures. PMID- 1461370 TI - Muscarinic receptor subtypes in bovine adrenal medulla. AB - Catecholamine secretion in the bovine adrenal medulla is evoked largely by nicotinic receptor activation. However, bovine adrenal medulla also contain muscarinic receptors that mediate several cell responses. To understand the physiological role of muscarinic receptors in the bovine adrenal medulla it is important to identify the pharmacological subtypes present in this tissue. For this, we analyzed the abilities of different selective muscarinic antagonists in displacing the binding of the non-selective antagonist [3H] quinuclidinyl benzylate to an enriched plasma membrane fraction prepared from bovine adrenal medulla. All the selective antagonists bind at least two bindings sites with different affinities. The binding profile of the sites with high proportion is similar to the M2 subtype and those present in low proportion have a M1 profile. However, some variation in the proportion of the sites for the different ligands suggest the presence of the third pharmacological subtype (M3). We conclude that the sites in high proportion (60-80%) correspond to M2 muscarinic subtypes, and the rest is constituted by M1 plus M3 subtypes. The presence of multiplicity of subtypes in the adrenal medulla membranes suggests a diversity of functions of muscarinic receptors in the adrenal gland. PMID- 1461371 TI - D-penicillamine affects lipid peroxidation and iron content in the rat brain cortex. AB - D-Penicillamine, a trifunctional amino acid known for its ability to form metal complexes and for being a radical scavenger, has been investigated "in vitro" and "in vivo" in the rat brain cortex. At 50 microM the drug facilitated lipid hydroperoxides and TBARS formation in brain cortex homogenates, while at higher concentrations a clear inhibition of the lipid peroxidative process was observed. The activity of the D-penicillamine (25 and 50 mg/Kg i.p.) was evaluated "in vivo" after a 7-day treatment in rats in whose brain cortex a slow process of lipid peroxidation was induced by iron-saccharate injection. Lipid hydroperoxides, lipid soluble fluorescent compounds and the iron content of both iron-injected and contralateral hemicortices showed a significant decrease in comparison to rats untreated with D-penicillamine. The higher dose also induced in normal rats a significant decrease in basal TBARS and iron content of the brain cortex. In the iron-injected cortex the observed Fe2+/Fe3+ ratio was significantly different from that of normal rats. On the contrary ratios obtained form D-penicillamine treated animals were higher in comparison to both normal and iron-injected animals. These results suggest that D-penicillamine, acting as a reducing agent, inhibits the iron redox system and, as a chelating agent, can remove metal from action sites where lipid peroxidation may occur. PMID- 1461372 TI - A unique hydrophobic domain of rat brain globular acetylcholinesterase for binding to cell membranes. AB - Both salt-soluble and detergent-soluble rat brain globular acetylcholinesterases (SS- and DS- AChE EC 3.1.1.7) are amphiphiles, as shown by detergent dependency of enzymatic activity and binding to liposomes. Proteinase K and papain treatment transformed SS-AChE and DS-AChE into forms that, in absence of detergent, no longer aggregated nor bound to liposomes. In contrast, phosphatidylinositol specific phospholipase C had no effect on these properties. Labeling DS-AChE with 3-(trifluoromethyl)-3-(m-(125I)-iodophenyl) diazirine ([125I]TID) revealed, by polyacrylamide gel electrophoresis under reducing conditions, one single band of 69 kD apparent molecular mass. The same pattern was previously obtained with Bolton and Hunter reagent-labeled enzyme. Proteinase K treatment transformed the 11 S [125I]TID labeled AChE into a 4 S form which no longer showed 125I radioactivity and was unable to bind to liposomes. These results are compatible with the existence of a hydrophobic segment present both on salt-soluble and detergent-soluble 11 S AChE as well as on the minor forms 4 S and 7 S. This segment is not linked to the catalytic subunits by disulfide bounds in contrast to the 20 kD non-catalytic subunit described by Inestrosa et al. PMID- 1461374 TI - New insights into the cause of Parkinson's disease. AB - Current concepts as to the cause of Parkinson's disease (PD) suggest an inherited predisposition to environmental or endogenous toxic agents. Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. Which of these is the primary event, generating a secondary cascade of changes culminating in nigral cell death, is unknown. In presymptomatic Lewy body-positive control brains, the nigra shows depletion of reduced glutathione content and, possibly, a reduction of complex I activity. Whatever the significance of these various abnormalities, be they causal or secondary, they provide novel targets for the development of new strategies to treat the cause of PD. PMID- 1461373 TI - [3H] cocaine labels a binding site associated with the serotonin transporter in guinea pig brain: allosteric modulation by paroxetine. AB - We studied the characteristics of [3H]cocaine binding to membranes prepared from whole guinea pig brain. Cocaine binding was specific and saturable. A one-site binding model fit the data adequately: the Kd value of [3H]cocaine was 44 nM with a Bmax value of 280 fmol/mg protein. The rank order of potency for the [3H]cocaine binding site was paroxetine > clomipramine > (-)-cocaine > fluoxetine > mazindol > desipramine > GBR12909 > phencyclidine > benztropine > GBR12935 > (+)-cocaine. The IC50 values of these drugs for inhibition of [3H]cocaine binding were highly correlated with their IC50 values for inhibition of [3H]5-HT uptake into synaptosomes prepared from whole guinea pig brain. High affinity 5-HT uptake inhibitors produced dose-dependent wash-resistant (pseudoirreversible) inhibition of [3H]cocaine binding. The wash-resistant inhibition produced by paroxetine was due to an increase in the Kd of [3H]cocaine binding sites, and was accompanied by an increase in the dissociation rate, consistent with an allosteric mechanism. These studies suggest that, using membranes prepared from whole guinea pig brain, [3H]cocaine labels a binding site associated with serotonin transporter and that paroxetine and cocaine bind to different sites on the serotonin transporter. PMID- 1461375 TI - Arterial delivery of myoblasts to skeletal muscle. AB - One of the major limitations of myoblast implantation as a therapy for muscular disease is that multiple injections by intramuscular implantation may be required for widespread delivery of cells. Also, some sites (eg, the diaphragm) are relatively inaccessible to injection. As an alternative, we have undertaken intra arterial administration of myoblasts. For these experiments, we used donor cell myoblasts from the immortal L6 cell line labeled with lacZ via the beta-gal-at gal retrovirus. In our model, target rat skeletal muscle (tibialis anterior [TA]) was injured using 0.5 ml of 0.5% bupivacaine and 15 IU of hyaluronidase; saline was injected into the contralateral side as a control. We infused 3 x 10(6) lacZ positive cells into the abdominal aorta of previously injured, immunosuppressed (cyclosporine A) rats. At 7, 14, and 28 days, TA, liver, heart, lung, and spleen were examined for lacZ staining. In both the injured and control muscles, a few differentiated, lacZ-positive muscle cells were present, both singly and in groups, at each time point. These studies demonstrate that genetically labeled, transformed myoblasts may migrate from the arterial circulation to muscle and fuse there to form differentiated muscle cells. It is conceivable that intra arterial delivery of myoblasts may have a role in the therapy of selected diseases of skeletal muscle. PMID- 1461376 TI - Hemimasticatory spasm: clinical and electrophysiologic observations. AB - Hemimasticatory spasm is a rare disorder of the trigeminal nerve that produces involuntary jaw closure due to paroxysmal unilateral contraction of jaw-closing muscles. We report three patients with this disorder. Electrophysiologic studies demonstrated normal blink and masseter reflexes. The masseter inhibitory reflex was absent during periods of spasm. Needle electromyography demonstrated irregular bursts of motor unit potentials that were identical to the pattern observed in hemifacial spasm. The electrophysiologic findings suggest ectopic excitation of the trigeminal motor root or its nucleus, an abnormality that is analogous to ectopic excitation of the facial nerve in hemifacial spasm. One patient improved temporarily with surgery, one improved while on treatment with carbamazepine, and another responded favorably to botulinum toxin injection. PMID- 1461377 TI - Cerebellar diaschisis revisited: pontine hypometabolism and dentate sparing. AB - A unilateral supratentorial lesion may cause hypometabolism in the contralateral cerebellar hemisphere (crossed cerebellar diaschisis). We analyzed glucose metabolism, measured by PET-FDG, in the posterior fossa in 67 patients (78 PET studies) with primary unilateral supratentorial brain tumors selected for visually obvious metabolic asymmetry in the cerebellar hemispheres. We found that glucose utilization was 17% lower in the contralateral cerebellar cortex (compared with the ipsilateral one), consistent with the selection criterion, and 19% lower in the ipsilateral pons, wherein lie the first order synapses of the corticopontocerebellar pathway. This finding helps to validate the prevalent view that cerebellar diaschisis is due to interruption of afferent input from the corticopontocerebellar pathway. However, glucose metabolism in the contralateral dentate nucleus was relatively preserved--only 2% less than the ipsilateral dentate. This "dentate sparing" suggests preservation of afferent input to the largest of the deep cerebellar nuclei from the Purkinje cells in the cortex, despite interruption of the major excitatory input to the Purkinje cells. PMID- 1461378 TI - Vertigo and the anterior inferior cerebellar artery syndrome. AB - We present two patients with clinical features of infarction in the distribution of the anterior inferior cerebellar artery (AICA) who had vertigo as an isolated symptom for several months prior to infarction. Both had risk factors for cerebrovascular disease and other episodes of transient neurologic symptoms not associated with vertigo. At the time of infarction they developed vertigo, unilateral hearing loss, tinnitus, facial numbness, and hemiataxia. MRI identified hyperintense lesions in the lateral pons and middle cerebellar peduncle on T2-weighted images. Audiometry and electronystagmography documented absent auditory and vestibular function on the affected side. Since the blood supply to the inner ear and the vestibulocochlear nerve arises from AICA, a combination of peripheral and central symptoms and signs is characteristic of the AICA infarction syndrome. The vertigo that preceded infarction may have resulted from transient ischemia to the inner ear or the vestibular nerve. PMID- 1461379 TI - Accuracy and interobserver reliability of scalp ictal EEG. AB - We studied the accuracy and reliability of scalp ictal EEG in 137 complex partial seizures (119 temporal and 18 extratemporal) in 35 patients in whom we knew the correct site of seizure origin because all patients had been seizure-free for more than 2 years after seizure surgery. Three electroencephalographers independently determined side of seizure origin based on activity at onset of electrographic seizure (ASO), rhythmic theta and alpha (RTA), postictal findings (PIF), and the electrographic seizure as a whole. When all seizures were analyzed, including those with generalized features or obscured by artifact, we determined side of seizure onset correctly in 76% to 83% of temporal seizures and 47% to 65% of extratemporal seizures. In most of the remainder, a lateralization judgment was impossible. When analysis was confined to those seizures in which lateralization was possible, we correctly lateralized 93% to 99% of temporal seizures and 89% to 100% of extratemporal seizures. Interobserver reliability was excellent. RTA and PIF were more accurate than ASO. RTA was significantly more common in temporal seizures. Our data indicate that lateralization by scalp EEG is highly accurate and reliable. PMID- 1461380 TI - A clinical staging classification for type C Niemann-Pick disease. AB - Analysis of the temporal sequence of neurologic events, neurophysiologic abnormalities, and longevity in 36 Niemann-Pick type C patients revealed two clinical subgroups with five stages of severity within each group. Patients with a preschool onset (group I; n = 18) had a higher mortality than did patients with a school-age onset (group II; n = 18). An asymptomatic phase (stage 0) was defined by biochemical and histopathologic evidence of disease. The initial manifestations of stage 1 were a movement disorder (group I) and cognitive difficulties (group II) accompanied by impaired vertical saccadic eye movements and abnormal acoustic reflexes. Stage 2 was characterized by the sequential occurrence of vertical supranuclear gaze palsy (VSGP), cognitive difficulties, and dysarthria in group I and a movement disorder, VSGP, and dysarthria in group II. Pyramidal tract signs and abnormal brainstem auditory evoked responses defined stage 3 in both groups. Stage 4 culminated in a nonambulant, vegetative state. PMID- 1461381 TI - Possible use of CSF glycosphingolipids for the diagnosis and therapeutic monitoring of lysosomal storage diseases. AB - We used a high-performance liquid chromatography method to measure CSF gangliosides, neutral glycolipids, and sulfatides in patients with lysosomal storage disorders. These measurements could be done on less than 1 milliliter of CSF. In patients with GM1 gangliosidosis, GM1 ganglioside was increased, and in GM2 gangliosidosis patients, GM2 ganglioside was increased in CSF. Sulfatides were variably increased in CSF early in the course of the disease and appeared to be a means of monitoring patients, following bone marrow transplantation. Fabry's disease patients showed an increase in globotriaosylceramide, but Krabbe's disease patients did not demonstrate an increase in galactosylceramide. This study suggests that CSF glycosphingolipid measurements may prove helpful in the diagnosis and monitoring of lysosomal storage diseases. PMID- 1461382 TI - Trisomy 17p associated with Charcot-Marie-Tooth neuropathy type 1A phenotype: evidence for gene dosage as a mechanism in CMT1A. AB - Charcot-Marie-Tooth neuropathy type 1A (CMT1A) is associated with a DNA duplication on chromosome 17, band p11.2, resulting in partial trisomy for this region in CMT1A patients. The 17p11.2 duplication may lead to the CMT1A phenotype either through disruption of a gene at the duplication breakpoint junction or by trisomic dosage and overexpression of a gene within the duplication. To test the latter model, we evaluated a patient with complete translocation trisomy 17p for signs of CMT1A. In addition to the dysmorphic features seen in trisomy 17p, a neurologic examination and electrophysiologic studies detected a demyelinating neuropathy, compatible with CMT1A. A karyotype on the patient's father found a balanced translocation [t(14;17)] with breakpoints on chromosome 17 in either band p11.1 or proximal p11.2. An analysis of the patient's DNA confirmed trisomy 17p and mapped the translocation breakpoint to a region in 17p11.2, proximal to the duplication breakpoint in CMT1A. Our observations in this patient with trisomy 17p are relevant to an understanding of the genetic mechanism in CMT1A and provide strong evidence that gene dosage through segmental trisomy for 17p11.2 results in the CMT1A phenotype. PMID- 1461383 TI - Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy. AB - X-linked spinal and bulbar muscular atrophy (SBMA), a motor neuron disease associated with androgen insensitivity, is caused by androgen receptor gene mutations with an increased number of tandem CAG repeats in exon 1. We investigated the increased number of CAG repeats in androgen receptor genes of 19 SBMA patients and found that this correlated strongly with the age at onset of muscle weakness. Thus, SBMA is the first genetic disease in which a strong correlation between the degree of genetic abnormality (number of CAG tandem repeats) and clinical phenotypic expression is demonstrable. The results further indicate that androgen gene mutation is directly involved in the degeneration of motor neurons. PMID- 1461384 TI - Severe phenytoin hypersensitivity with myopathy: a case report. PMID- 1461385 TI - Superior sagittal sinus thrombosis in a child with protein S deficiency. PMID- 1461386 TI - Denervation in paraplegia. PMID- 1461387 TI - Abscesses and thalamic pain. PMID- 1461388 TI - [Etiopathogenic, physiopathologic, and clinical aspects of perianesthetic malignant hyperthermia and related forms]. PMID- 1461389 TI - [Susceptibility to malignant hyperthermia: diagnostic aspects and practical implications]. PMID- 1461390 TI - [Prevention of the clinical forms of malignant hyperthermia and safe anesthesia]. PMID- 1461391 TI - [Death caused by malignant hyperthermia and approaches of the Italian judiciary]. PMID- 1461392 TI - [Guidelines for the treatment of the "hyperthermic" patient: the S.I.A.A.R.T.I. recommendations"]. PMID- 1461393 TI - Regional anesthesia in pain therapy. PMID- 1461394 TI - [Peripheral block with electric neurostimulation]. PMID- 1461395 TI - [Loco-regional anesthesia and postoperative pain]. PMID- 1461396 TI - [Free radicals and lipoperoxidation]. PMID- 1461397 TI - [Lipoperoxidation in multiple organ failure: experimental model]. PMID- 1461398 TI - [Cytokines and lazaroids]. PMID- 1461399 TI - [Protective action of 21-aminosteroids in post-ischemic shock (splanchnic artery occlusion). Experimental model]. AB - In anesthetized Wistar female rats a post-ischemic shock have been induced by splanchnic artery occlusion (S.A.O.). In these condition all animals died at 90 min., past release of occlusion and splanchnic reperfusion. 100% of pretreated rats with 21-Aminosteroids (U74389F) at doses of 1.5 mg.kg-1 survive over 3-6 hours, and 50% over 12 hours. Moreover, TNF alpha in these animals decrease significantly (p < 0.05). These results shown that 21-Aminosteroids can cause protective activity on lipoperoxidative damage in post-ischemic shock. PMID- 1461400 TI - [Anesthesia and pregnancy in oral medicine]. PMID- 1461401 TI - [Relative analgesia with nitrogen monoxide in oral dentistry]. PMID- 1461402 TI - [Conscious sedation with benzodiazepine]. PMID- 1461403 TI - [Difficult intubation in maxillo-facial surgery]. PMID- 1461404 TI - [Objectives in cardiopulmonary resuscitation education]. PMID- 1461405 TI - [Treatment of anaphylactic shock]. PMID- 1461406 TI - [Systemic complications of local anesthetics]. PMID- 1461407 TI - [Cardiologic emergencies in oral medicine]. PMID- 1461408 TI - [Anesthesiologic approach and prevention in dental procedures in patients with blood coagulation disorders]. PMID- 1461409 TI - [Cranio-facial neuralgia and problems in oral medicine. Value of a multidisciplinary approach]. PMID- 1461410 TI - [Tutorial: "monitoring depth of anesthesia"]. PMID- 1461411 TI - [Spinal anesthesia and prophylaxis of venous thromboembolism. Results of a national survey]. PMID- 1461412 TI - [Pain treatment in the patient with vascular disease]. PMID- 1461413 TI - [Non-surgical treatment of peripheral vascular diseases: diabetic foot and hyperbaric oxygenation]. PMID- 1461414 TI - [General anesthesia in carotid endarterectomy]. PMID- 1461415 TI - [Methods for protecting the spinal cord in surgery of the thoraco-abdominal aorta]. PMID- 1461416 TI - [Perioperative pressure variations during carotid thromboendarterectomy]. PMID- 1461417 TI - [The neuromuscular plate: up-date synthesis]. PMID- 1461418 TI - ["Instrumental methods of transplantation legislation"]. PMID- 1461419 TI - [Behavior of the rotatory circuit with the techniques in low flows and closed circuit]. PMID- 1461420 TI - [Monitoring and oxygen consumption in closed-circuit anesthesia]. PMID- 1461421 TI - [Preoperative evaluation of the patient]. PMID- 1461422 TI - [Immunotherapy of sepsis with the anti-endotoxin monoclonal antibody Centoxin. . Preliminary results of the Italian experience]. PMID- 1461423 TI - ["Biosis--historic evolution of a concept"]. PMID- 1461424 TI - ["Is it adviceable to code the limits of recovery in resuscitation?]. PMID- 1461425 TI - [Vegetative state: diagnostic aspects and ethical problems]. PMID- 1461426 TI - [The anesthetist-resuscitator between ethics--biotechnology and juridical problems]. PMID- 1461427 TI - [The blood transfusion program in anesthesia: introduction and presentation]. PMID- 1461428 TI - [Physiology of the low hematocrit]. PMID- 1461429 TI - [Controversial elements in a blood transfusion program]. PMID- 1461430 TI - [Role of the transfusionist in the blood transfusion program in anesthesia]. PMID- 1461431 TI - [Role of the anesthetist in a blood transfusion program]. PMID- 1461432 TI - [Volemic support in preoperative blood donation]. PMID- 1461433 TI - [The hospital blood transfusion committee: experiences and proposals]. PMID- 1461434 TI - [Validity of cardioactive glycosides]. PMID- 1461435 TI - [The new inotropic agents]. PMID- 1461436 TI - [Phosphodiesterase inhibitors]. PMID- 1461437 TI - [Inotropic agents - transport and consumption of oxygen]. PMID- 1461438 TI - [Inotropic treatment in heart transplantation]. AB - The safe conduct of anesthesia and intensive care for heart transplant recipient requires a sound understanding of the pathophysiology of advanced cardiac failure through knowledge of anesthetic and cardiovascular pharmacology and an appreciation of the altered physiologic and pharmacologic responses of acutely denervated and transplanted heart. The most serious dysfunction is acute distension and failure of the transplanted heart's right ventricle. Hemodynamic monitoring and TEE are useful in the management of inotropic support during heart transplantation. PMID- 1461439 TI - [Current aspects and perspectives of the therapy with inotropic agents]. PMID- 1461440 TI - [Weaning from mechanical artificial ventilation in chronic bronchopneumopathies]. PMID- 1461441 TI - [Pharmacokinetics and pharmacodynamics of the most recent curare agents]. PMID- 1461442 TI - [Clinical semeiotics of curarization]. PMID- 1461443 TI - [Instrumental monitoring and decurarization]. PMID- 1461444 TI - [Is priming a useful method?]. PMID- 1461445 TI - [Pathologic conditions that interfere with the action of curare-like agents]. PMID- 1461446 TI - [Clinical nutrition today: metabolic and nutritional effects]. PMID- 1461447 TI - [Enteral nutrition in intensive care units: advantages of a high calorie density diet]. PMID- 1461448 TI - [Nutritional support in patients with thoracic trauma: usefulness of an enteral diet with a high fat content]. PMID- 1461449 TI - [Kinetics of lipid emulsions]. PMID- 1461450 TI - [Effects of lipid emulsions on the defense mechanisms of the host]. PMID- 1461451 TI - [Effectiveness of early enteral nutrition in the prevention of stress ulcer]. PMID- 1461452 TI - [Hypothermia in anesthesia, resuscitation, and in emergency situations]. PMID- 1461453 TI - [Myofascial pain syndromes of the head and neck. Nosographic assessment]. PMID- 1461454 TI - [Myofascial pain syndromes of the head and neck: differential diagnosis]. PMID- 1461455 TI - [Changes in the tonic postural system in subjects with evidence of pain trigger points of the head and neck]. PMID- 1461456 TI - [Anesthesia of the epileptic patient]. PMID- 1461457 TI - [Anesthesiologic treatment of the patient with cerebrovascular insufficiency]. PMID- 1461458 TI - [Myorelaxants in neurologic diseases]. PMID- 1461459 TI - [Resuscitation treatment in status epilepticus]. PMID- 1461460 TI - [Diffuse axonal injury (DAI): diagnostic assessment with nuclear magnetic resonance (NMR)]. PMID- 1461461 TI - [Standards and legislation of hyperbaric medical services]. PMID- 1461462 TI - [Critical monitoring in hyperbaric therapy: analysis of the problems]. PMID- 1461463 TI - [Hyperbaric oxygen therapy in severe infections]. PMID- 1461464 TI - [The role of hyperbaric oxygen therapy in carbon monoxide poisoning under the light of the scientific literature of the past 70 years]. PMID- 1461465 TI - [Compartment syndrome: assessment and role of hyperbaric oxygen]. PMID- 1461466 TI - [The treatment of arterial gas embolism with hyperbaric oxygenation]. PMID- 1461467 TI - [Diagnosis of the cerebral ischemic syndromes and hyperbaric oxygen therapy]. PMID- 1461468 TI - [Hyperbaric emergency: concepts of physiopathology]. PMID- 1461469 TI - Haemodynamics of intravenous anaesthetics. PMID- 1461470 TI - [Intravenous anesthetics and respiratory mechanics]. PMID- 1461471 TI - Assessment of possible anaphylactic reactions to i.v. anaesthetic agents. PMID- 1461472 TI - [Different anaesthetic technique: conduction and outcome from multidisciplinary procedures]. AB - Different anesthetic techniques in perioperative times (intraoperative induction and maintenance of anaesthesia, recovery and 24 and 48 postoperative hours) were evaluated in 100 patients underwent general surgery. After randomization, 4 groups were clinically and statistically compared according to anesthesia technique (propofol + fentanyl in air/O2; isoflurane + fentanyl in air/O2; propofol + fentanyl in N2O/O2; isoflurane in N2O/O2). The results show that conduction of anesthesia without N2O is difficult; but the adequacy of induction and maintenance of anesthesia, the speed of recovery and the quality in the postoperative period show no difference in the anesthesia techniques used. PMID- 1461473 TI - Obstetric anesthesia. PMID- 1461474 TI - [Cardiac anaesthesia: drugs and techniques]. PMID- 1461475 TI - Anaesthesia for neurosurgical procedures. PMID- 1461476 TI - A.R.D.S. PMID- 1461477 TI - Intravenous anaesthetics in anaesthesia and ICU: cerebral mapping, TCD and ICP. PMID- 1461478 TI - [Sedative therapy in intensive care units: hormonal and metabolic implications]. PMID- 1461479 TI - Critically ill patients and fat emulsions. AB - In critically ill patients, lipid tolerance may be impaired. In ICU, patients are usually given TPN including fat emulsions. If sedation with propofol is given simultaneously the fat load increases and may exceed the maximal clearing capacity of exogenous fat emulsion unless the administration of the parenteral fat is adjusted to take account of the lipid contained in propofol. An accumulation of fat may result in the so-called 'fat overload syndrome'. Close monitoring of serum triglyceride concentration is therefore recommended to avoid fat overload. PMID- 1461480 TI - [Safety in pediatric intravenous anesthesia]. PMID- 1461481 TI - [Cytokines in ICU. Our experience]. PMID- 1461482 TI - [The anesthesiology work station]. PMID- 1461483 TI - [Specialized applications and information systems]. PMID- 1461484 TI - In search of quality--people and processes towards a unified dataset. PMID- 1461485 TI - Computer controlled drug infusion--value and safety. PMID- 1461486 TI - [Bioethics: definition of death]. PMID- 1461487 TI - [Organ transplantation in Italy and donation problems]. PMID- 1461488 TI - [Current laws as a technical and organizational guide for organ procurement and transplantations]. PMID- 1461489 TI - [Clinical diagnosis of the status of brain death]. PMID- 1461490 TI - [Brain death status and spinal reflexes]. PMID- 1461491 TI - [Radioisotope techniques for the diagnosis of brain death]. PMID- 1461492 TI - [Intracranial flowmetry study in coma and brain death]. PMID- 1461493 TI - [SjBO2 and biohumoral parameters in coma and death]. PMID- 1461494 TI - [Preliminary results of a multicenter study on cure profiles and outcome in patients treated in intensive care units. GiViTI. Gruppo Italiano per la Valutazione degli Interventi in Terapia Intensiva]. PMID- 1461496 TI - Experimental therapy of acute brain neurodegeneration. PMID- 1461495 TI - Oxygen derived free radicals and excitatory amino acids in the pathogenesis of ischemia induced neuronal death. PMID- 1461497 TI - Cerebral plasticity: the neurosurgical viewpoint. PMID- 1461498 TI - [Neurosedation and neuroprotection]. PMID- 1461499 TI - [Cytokines and ARDS]. PMID- 1461500 TI - [Physiopathology of pulmonary embolism]. PMID- 1461501 TI - [Pulmonary embolism in orthopedics and traumatology]. PMID- 1461502 TI - [Pulmonary embolism in obstetrics and gynecology]. PMID- 1461503 TI - [Pulmonary embolism: combined diagnostic imaging]. PMID- 1461504 TI - [Radioisotope techniques in the diagnosis of pulmonary embolism]. PMID- 1461505 TI - [Pulmonary embolism: therapeutic strategies in intensive care]. PMID- 1461506 TI - [Evolution of circuits in anesthesia]. PMID- 1461507 TI - [Semi-open circuit, low flows, closed circuit: anesthesia circuits]. PMID- 1461508 TI - [Clinical use of minimal flows]. PMID- 1461509 TI - [Operating room pollution during closed-circuit anesthesia]. PMID- 1461510 TI - [Acute respiratory insufficiency in AIDS in intensive care]. PMID- 1461511 TI - [Therapeutic protocols in resuscitation in patients with AIDS]. PMID- 1461512 TI - [Respiratory resuscitation in AIDS today]. PMID- 1461513 TI - [Esophageal achalasia: cardiomyotomy or pneumatic dilatation?]. AB - Sixty-four patients with achalasia of the esophagus were surgically treated during the period 1973-1990. They were analyzed a late follow-up (mean = 78 months) by means of subjective and objective parameters. The Authors emphasize the efficiency of the diagnostic approach so that surgical treatment offers better results. The surgical technique of choice consists of an anterior esophagomyotomy (extending from 6 cm above the esophagogastric junction down to 1 2 cm below it) with the addition of an anterior Dor antireflux procedure through a laparotomy. The other therapeutic approach to achalasia is pneumatic dilatation of lower esophageal sphincter. A retrospective comparison of two different treatments is made through the analysis of the literature (medlars 1986-1990). Relief of dysphagia is reported in 92.78% of patients treated by myotomy and in 78.71% of those treated by forceful dilatation. The morbidity rate is greater after pneumatic dilatation (6% vs 5%) and the mortality rate is 1.1% after myotomy and 0.2% after dilatation. There are not rigorous criteria of choice between the two treatment methods but the Authors indicate that Heller's myotomy with an antireflux procedure achieve better and lasting results. PMID- 1461514 TI - [Carcinoma of the surgically treated stomach. Our experience]. AB - Between 1977 and 1991, 12 patients (11 males and 1 female; median age of 62.7 years) with gastric stump cancer were observed. All patients were previously operated for benign gastric (4) or duodenal (8) ulcer disease. Median duration interval between first operation and the diagnosis of gastric carcinoma was 22.0 years (range 7-39 years). Only in 5 patients total gastrectomy was carried out. Two out of these 5 patients are still alive at 2 and 24 months after surgery, while the median survival of remaining patients was about 9 months. The usefulness of close follow-up and digestive endoscopy in peptic ulcer patients who had surgical treatment is considered in order to detect an early gastric stump cancer. PMID- 1461515 TI - [Leiomyoma of the esophagus]. AB - In this paper the Authors report a review of the clinical records from 1972 to 1985 of the Institut of IV Clinica Chirurgica of Rome of esophageal leiomyoma. We report on 7 cases: three males and four females. Their ages ranged from 37 to 78 years (mean 54 years). The most frequent symptoms were dysphagia (71.4%), loss weight (57.1%) and slight epigastralgia (42.8%). Barium meal, esophagoscopy, esophageal manometry, TAC are the most sensitive procedures for a correct preoperative diagnosis. The therapy of choice is surgical treatment. However surgery is conservative: extramucosal enucleation of the leiomyoma is the procedures of choice. The postoperative course was free of complications, the long-term results were excellent. PMID- 1461516 TI - [Acute disorders of the biliary tract in geriatric patients]. AB - Acute pathologies of the biliary tract in geriatric patients were examined in this study taking into account the major causes, treatment used and results obtained. All patients aged over 65 who had been hospitalised during the past 17 years for acute pathologies of the biliary tract (564 cases, equivalent to 34.2% of all in-patients suffering from acute biliary pathologies) were included in the study. These patients were then subdivided into 3rd and 4th age groups (65-74 and < 75 years respectively). The results obtained in the 3rd age group (267 patients, 60%) showed the greatest number of cases of inflammatory lithiasic disease of the cholecystus (61.2%) and VBP (17.7%), whereas 45 patients, equivalent to 49.5%, presented tumours with jaundice. Out of a total of 179 cases in patients in the 4th age group, equivalent to 39.3%, 119 (66.5%) were suffering from lithiasic cholecystitis and 16 (8.9%) from calcolosis of the VBP with jaundice. Cancer of the pancreas head was diagnosed in 27 patients (58.7%), whereas 9 (19.6%) had obstruent cancer of the biliary tract. The Authors conclude that both the preoperative preparation, the choice of operation and postoperative treatment give satisfactory results with a very low early mortality (0.8% in non tumour cases and 6.9% in tumour cases). PMID- 1461517 TI - [Endoscopic and intraoperative ultrasonography in staging of stomach neoplasms]. AB - In Japan a better prognosis of gastric cancer has been achieved by early diagnosis and wide, careful lymphectomy. This is not true in western countries. Thus the Authors believe that rational surgical strategy and the careful use of advanced diagnostic tools would produce a better outcome. The Authors report the new diagnostic methods that they adopt in every case of gastric neoplasm: endoscopic ultrasonography, which also proved useful in submucosal tumors, like lymphomas; parenteral nutrition, immune status assessment for a possible use of immune response modulators, single-dose antimicrobial prophylaxis, antithrombotic prophylaxis, autologous blood storage, in order to reduce transfusion-linked risks. Surgical strategy is also reported, which includes wide resection with adequate margins, R2 lymphectomy and intraoperative assessment of disease extension by ultrasonography. PMID- 1461518 TI - [Permanent expanders in esthetic, corrective and reconstructive surgery of the breast]. AB - Since 1986 we used the permanent expandable implant (PEI) as the first choice of prosthesis in breast surgery. The possibilities offered by multiple over expansions and deflations have been explored: 224 PEI were utilized in 162 patients for aesthetic (38 with bilateral hypoplasia), corrective (20 with asymmetry, tubular breasts or Poland's Syndrome) and reconstructive breast surgery (104 patients for immediate and delayed reconstruction following radical, modified radical, partial and subcutaneous mastectomy). All implants were positioned submuscularly; a latissimus dorsi flap was transposed when pectoralis major was absent or damaged. Either the Becker or the Gibney implant was used. All PEI were immediately or progressively overinflated by 25-80% and then deflated to the planned volume. Twenty-two patients developing capsular contracture were treated by overinflations and deflations with subjective and objective improvement. Many of augmentation mammaplasty patients refused implant deflation to the planned preoperative volume. The over-expansion/deflation process proved to be effective in obtaining ptosis, in maintaining permanent volume symmetry and in keeping the base of tubular breast unfolded. PMID- 1461519 TI - [Review of the surgical techniques used for the treatment of breast hypertrophy]. PMID- 1461520 TI - [Latero-terminal anastomosis in colorectal surgery using a mechanical stapler. Technical note]. AB - Following a discussion of the various methods of colorectal anastomosis in cancer surgery, the Authors describe a technical variant using a mechanical stapler in a high rectal location. The rapidity of anastomosis as well as the decreased risk of dehiscence, fistula and stenosis are underlined. PMID- 1461521 TI - [Clamping the suprahepatic inferior vena cava in emergency surgery. Technical note]. AB - In major hepatic surgery the temporary exclusion of the vena cava may be achieved using a variety of more or less complex procedures. Alternatively, for use above all in emergency surgery, the paper illustrates a method of clamping the suprahepatic inferior vena cava using a left lateral route, which is quick to carry out and undoubtedly efficient. PMID- 1461522 TI - [Deep vein thrombosis in surgery]. AB - Deep vein thrombosis is still an underestimated and often unrecognised diseases both in Italy and abroad despite being far from rare and in spite of its severe complications and often disabilitating sequelae. It is a disease which is becoming more frequent due to increased life expectation, the larger number of operations on elderly patients, and the increased frequency of limb injuries. General and specialised surgery is often hampered by this complication. This has raised interest in a more detailed knowledge of the mechanisms leading to DVT, and the correct employment of the latest equipment which enable diagnosis to be made and daily monitoring of the disease during its evolution. But the greatest efforts must be reserved for preventive measures in order to achieve a statistically significant reduction in the incidence of the disease in operated patients. It is to be hoped that a greater awareness of thromboembolic diseases will allow this to be achieved in the future. PMID- 1461523 TI - [Optimal dose of amino acids administered in total parenteral nutrition (TPN) of malnourished patients]. AB - A plasmatic concentration for each aminoacid, between 1 and 1.5 times the normal value in fasting healthy subjects, is considered as an optimal target during total parenteral nutrition (TPN) in malnourished patients. We have analyzed the correlation between the aminoacid input and the aminoacid plasmatic concentration during TPN at different aminoacid composition. By exponential regression curves we then calculated the input required to keep each aminoacid plasma concentration in the optimal range. PMID- 1461524 TI - [Primary carcinoma of the cystic duct. A rarity in surgery]. AB - The Authors describe a case of primary carcinoma of the cystic duct as reported in the data od another 29 cases described in literature. The subjects it generally strikes are elderly men and its symptomatology is rather non specific. A preoperative diagnosis is as difficult as ever even with the aid of the most modern diagnostic techniques. The postoperative survival time is comparatively superior to other tumors of gallbladder and biliary tract, independently of the type of the surgical treatment adopts: cholecystectomy with the resection of the cystic duct associated less with lymphadenectomy and partial resection of the hepato-choledochus. PMID- 1461525 TI - [Cholestatic jaundice secondary to distention of the gallbladder caused by cystic duct syndrome]. AB - The Authors describe a rare case of cholestatic jaundice which persisted due to compression of the biliary tract by a hugely swollen gallbladder due to cystic duct syndrome. PMID- 1461526 TI - [Isolated neurofibroma of the stomach. Case report and review of the literature]. AB - An uncommon case of gastric neurofibroma is described: it was an incidental finding during assessment for abdominal pain, possibly due to pancreatitis, in a 58 year old man, with no sign of von Recklinghausen's disease. The generic diagnosis of gastric wall neoplasia was made by CT scanning; the neoplasm was resected with wedge resection of gastric wall. Histological and ultrastructural examination revealed a neurofibroma. Gastrointestinal stromal tumors are rare occurrence and usually are of smooth muscle derivation: a small percentage arises from nerve sheet, but such a distinction is never sharp. Neurogenic gastric tumors are usually benign and only 10% of von Recklinghausen associated neurofibromas can undergo malignant transformation. Wide excision of the tumor appears therefore the treatment of choice. PMID- 1461527 TI - [Pseudo-acute abdomen in familial Mediterranean fever. A case report]. AB - The Authors report a case of familial mediterranean fever with pseudo-acute abdomen recently observed and emphasize how a careful anamnesis can avoid unnecessary surgical intervention. PMID- 1461528 TI - [Lipoprotein(a): structure, metabolism and atherosclerotic disease]. AB - Lipoprotein(a) was discovered by chance by Berg in 1963; after twenty years of research, the chemical, physical and metabolic characteristics of Lp(a) are now known. This lipoprotein forms the missing link between the lipid metabolism and the coagulation-fibrinolysis process. The A. describe its similarity to plasminogen, its capacity to delay coagulum or embolus destruction and highlight its structural and functional similarity to lipid metabolism. To day, a total of 6 Lp(a) isoforms have been identified with different molecular weights: in addition, the inverse proportion between the isoforms' molecular weight and Lp(a) plasma concentration has been demonstrated. Lp(a) is not the product of the metabolism of other lipoproteins nor is it a catabolite of LDL; it is produced ex novo and does not apparently exchange its proteic fraction with other lipoproteins. The paper also examines the question of whether Lp(a) is a plasma marker which increases during the formation of atherosclerotic plaque or whether it should not be considered an atherogenetic factor. To this end the possible mechanisms by which Lp(a) is deposited in plaque are examined. Lastly, the paper reviews all studies concerning the relationship between Lp(a), ischemic cardiopathy and cerebrovascular disease. PMID- 1461529 TI - [Chronic hepatitis and liver cirrhosis]. AB - The Authors consider 349 liver biopsies; 32 of these showed cirrhosis. Patients with chronic hepatitis are at high risk for evolution to cirrhosis. Our aim is to establish the markers HBsAg and HBcAg comparing this with the risk groups and with the possible causes of cirrhosis. PMID- 1461530 TI - [Gastric and hematologic changes in patients with gastric parietal cell autoantibodies and non-insulin-dependent diabetes mellitus]. AB - Gastric abnormalities are more common in diabetics than in the normal population. They seem to be related to gastric parietal cell autoantibodies (GPCA). We have studied 168 patients affected with non-insulin-dependent diabetes mellitus (NIDDM), and assessed the GPCA in the serum and haematologic disorders. We have also assessed the endoscopic and histological findings of atrophic gastritis in patients with GPCA. GPCA were found in 15.74% of diabetic patients and in 2% of a control group of blood donors. 80% of GPCA positive patients showed signs of atrophic gastritis. Such presence of GPCA seems to be a good marker to identify patients affected by atrophic gastritis and its complications. PMID- 1461531 TI - [Influence of nutrition, age and vitamin D status on fasting urinary excretion of calcium in postmenopausal women]. AB - The purpose of the present study was to evaluate the influence of nutrition, age, and Vitamin D status on fasting urinary calcium (Ca) as a function of creatinine excretion (Ca/Cr) and of glomerular filtration rate (Ca/GFR) in postmenopausal women. Fasting urinary calcium, urinary Cr and GFR were measured in 18 women aged 54 to 91 years before and after six days of a calcium (400 mg/die) and sodium (100 mEq/die) restricted diet with a controlled content of proteins, lipids and glucides. Aged (over 64 y.) women having an adequate vitamin D status showed fasting urinary Ca/Cr and Ca/GFR after the controlled diet significantly lower than those showed before. It is concluded that fasting Ca/Cr and Ca/GFR may be nutrition-dependent. A revision of the significance of the fasting urinary Ca excretion is consequently suggested. PMID- 1461533 TI - [Neurological changes in aged patients with fractures of the femur: prevalence and clinical aspects]. AB - This study evaluates the prevalence and clinical significance of the main neurological diseases in 246 hospitalized elderly patients with hip fracture, who have to undergo rehabilitative treatment. Eighty-three patients already had clinically noticeable neurological diseases before fracture; they were compared to other components the survey. As for the type of fracture and surgical treatment, differences have not been found. Medical conditions have proved worse among neurological disease bearers; the same patients also had to run into more complications. What results from the study, considering the high prevalence of neurological diseases in patients with hip fractures, suggests that these neurological diseases are important risk factors for accidental falls and it's necessary to provide these patients with careful, continuous hospital assistance. PMID- 1461532 TI - [Gynecomastia]. AB - Gynecomastia is a benign pathology due to the increased volume of the mammary glands. The various etiological factors lead to an imbalanced estrogen/androgen ratio or to a greater local receptivity to the former with consequent hypertrophy of the mammary stromal gland components. Although the majority of cases are benign and/or transient, gynecomastia must be carefully examined using thorough anamnesis, hormone assays and instrumental tests in order to exclude local or further removed pathology. At present, medical or surgical therapy is reserved for those cases in which this condition is painful and/or psychologically damaging. In this study, following a review of the literature, the Authors focus on the etiological, diagnostic and therapeutic aspects of gynecomastia and illustrate the cases they have observed. PMID- 1461534 TI - [Reactive arthritis HLA B27 correlated in hospital patients in a general medicine department]. AB - We examined 14 cases of reactive arthritis seen during the four year period 1982/1985 out of a total of 7,380 admissions. The average age of the patients was 40.1 years, while hospitalisation averaged 15.6 days. More than half the patients presented oligoarthritis manifestations which were also characterized by asymmetry and migratory behavior. Visceral manifestations were noted in 10 of 14 patients (71.4%). Etiological diagnosis was arrived at in only two cases, whereas half the cases showed no positive enteral or urogenital infectious antecedents. The HLA B-27 determination resulted positive in 25% of the cases. This is highly significant (p < 0.01) when compared to the control group 4% positivity. The follow-up was carried out medially for 4 years in all patients and evidenced only one case of persistent joint inflammation at the knee level and another case of relapsing uveitis. This study, performed on a random group of patients hospitalized in a General Medicine Department, confirms for the most part data appearing in the literature. PMID- 1461535 TI - [Use of ultrafiltration in refractory cardiac decompensation]. AB - Traditional therapy for heart failure (diuretics, digitalic compound, vasodilators, inodilatory ACE-inhibitors) cannot arrest the progressive overloading of the circulatory system so that it is inevitable that a refractory stage to all forms of treatment will be reached when more specialised techniques, such as heart transplant and ultrafiltration will be needed. The paper reports the results obtained in 13 patients in ultrafiltration treatment for refractory heart failure: in the majority of these, a marked improvement in general conditions (edema, dyspnea) was recorded together with a regression from class 5 to class 3 NYHA in 5 patients, and to class 2 for others. The ultrafiltration method in spite of not altering the prognosis which remains negative in these patients, allow those waiting for heart transplant to survive and may improve their chances of surviving heart surgery. PMID- 1461536 TI - [Prevention of Pneumocystis carinii pneumonia with intermittent trimethoprim sulfamethoxazole]. AB - To evaluate efficacy and toxicity of intermittent trimethoprim-sulfamethoxazole (T/S) prophylaxis for Pneumocystis carinii pneumonia (PCP) our HIV-positive patients were given T/S (160 mg, 800 mg) twice daily for 3 consecutive days per week. Patients were included only if they met the CDC criteria for PCP prophylaxis, did not have intolerance to T/S, and if follow-up was 3 or more months. Thirty-eight patients received primary prophylaxis (Group I) for a mean period of 18.1 months and 26 patients received secondary prophylaxis (Group II) for a mean period of 15.5 months. Seventeen patients had adverse reactions (14 minor and 3 major reactions). PCP occurred in 1 patient in Group I after 20 months of T/S, and in 2 patients in Group II after 11 and 18 months of T/S. This pilot study suggests that intermittent T/S treatment is efficacious and relatively safe in the prophylaxis for PCP in HIV-positive patients. PMID- 1461537 TI - [Idiopathic hypereosinophilia syndrome: description of a clinical case and review of the literature]. AB - Idiopathic hypereosinophilia is a disease with an unknown etiology and pathogenesis and uncertain nosographic classification, although there is now tendency to group a number of syndromes under this name which were previously classified separately, although having similar hematological symptoms and clinical manifestations. The paper examines these aspects and reports the case of a patient with idiopathic hypereosinophilia to steroid treatment. PMID- 1461538 TI - [Asymptomatic bilateral occipital calcifications. A possible atypical form of Sturge-Weber-Krabbe syndrome?]. AB - Sturge-Weber-Krabbe syndrome is a rare congenital neuro-cutaneous disease which is characterized, in its full clinical expression, by facial naevus flammeus and epilepsy with mental retardation. Different atypical cases in which one or more symptoms are missing and clinical course is benign, have been reported in the literature in recent years. In the present paper a possible case of this syndrome radiologically diagnosed, without neurological and cutaneous symptoms, is reported; the importance of a more comprehensive study of this complex disorder, with particular attention to the incomplete forms, is stressed. PMID- 1461539 TI - [Clinical evaluation of a selective inhibitor of cholesterol synthesis: pravastatin]. AB - The recent introduction in clinical practice of a new class of drugs able to reduce the endogenous synthesis of cholesterol has undoubtedly made a noteworthy contribution to the treatment of hypercholesterolaemia which, as is well known, is one of the greatest risk factors in the natural history of atherosclerotic disease and of its cardiovascular complications. A last generation drug belonging to this family is pravastatin which differs from the other substances inhibiting the activity of the key enzyme of cholesterol metabolism, HMGCaA reductase, because of certain features of the molecule, such as hydrophilia and the fact it is already pharmacologically active at the moment of oral administration. Pravastatin, which is probably a special category of HMGCoA reductase inhibitor, has shown, in numerous experimental studies and controlled clinical trials, a notable effectiveness in reducing in a highly selective fashion the synthesis of cholesterol in the liver cells and consequently the number of cholesterol-rich lipoproteins in the systemic circulation, without also determining significant biologically negative side-effects. PMID- 1461540 TI - [Changes in lipid status during pravastatin treatment]. AB - Reduced cholesterolemia lowers the risk of ischemic cardiopathy, especially if LDL cholesterol levels are reduced. Today this effect can be achieved using drugs following the discovery of a new class of molecules: statins are specific inhibitors of HMG-CoA-reductase, a key enzyme in cholesterol biosynthesis. These molecules act by modifying the intracellular quota of cholesterol, especially at a hepatocytic level, thus enabling an enhanced expression of those genes responsible for forming receptors for membrane LDL with an increased number of receptors. This leads to a modulation of receptor activity which interferes with LDL uptake, promoting more rapid clearance. The aim of this study was to confirm the efficacy and tolerability of pravastatin when used for long periods in patients with high cholesterol levels, and to compare its activity to that of gemfibrozil. PMID- 1461541 TI - [Salivary and serum beta 2-microglobulin in the diagnosis of primary Sjogren's syndrome]. AB - beta 2-microglobulin (beta 2m) serum and salivary levels and total protein salivary levels were determined in 15 patients with primary Sjogren's syndrome (pSS), 14 patients with sicca syndrome and 11 healthy subjects. beta 2m serum and salivary levels were higher (p < 0.005) in the patients with pSS than in the healthy subjects and in the patients with sicca syndrome. The bioptic focus scores of minor salivary glands were correlated to beta 2m salivary levels with a high significance (p < 0.001) but were not correlated to beta 2m serum levels. The assessment of beta 2m serum and salivary levels is a non-invasive clinical investigation, which may be easily repeated. It is a very sensitive and highly specific test for the diagnosis of pSS. It may be therefore a useful mean to follow the natural course of pSS and to evaluate the effects of therapy. PMID- 1461542 TI - [Determination of serum procollagen-III peptide in chronic liver diseases. Clinical usefulness]. AB - Liver fibrosis determines the course and prognosis of chronic liver disease. Histological examination of liver biopsy is essential for diagnosing hepatic disease. Evaluation of serum concentration procollagen III peptides (sPIIIP) by radioimmunoassay (RIA) is a biochemical test useful for evaluating a fibrotic process. We have investigated 20 healthy subjects and 50 patients with chronic liver disease, histologically diagnosed by percutaneous liver biopsy: steatosis (8), fibrosteatosis (7), chronic persistent hepatitis (10), chronic active hepatitis (7), cirrhosis (18). SPIIIP levels were increased in patients with cirrhosis and chronic active hepatitis and in these groups of patients such levels were well correlated with histological activity of hepatic disease. Evaluation of serum concentration of PIIIP by RIA seems to be a useful test for evaluating a fibrotic process in chronic liver diseases evolving towards cirrhosis. PMID- 1461543 TI - [Hormonal markers of early-stage osteitis fibrosa in patients on hemodialysis]. AB - The diagnosis of renal osteodystrophy is straightforward when the disease has reached an advanced stage and the pathology is extremely difficult to treat, whereas it is considerably more complex during the early stages. A study was carried out to assess the sensitivity of some biochemical, hormonal and instrumental markers in the early diagnosis of osteitis fibrosa in patients undergoing hemodialysis due to chronic renal insufficiency. Of these markers, the assay of whole molecule PTH appeared to be the most sensitive and specific biological marker. PMID- 1461544 TI - [Efficacy and tolerability of nicardipine retard and captopril in hypertension in the aged. Results of a multicenter study]. AB - The efficacy and tolerability of nicardipine retard and captopril were assessed in 174 over-60-year-olds suffering from slight or moderate essential hypertension. After 2-3 weeks of wash out the patients were randomly assigned to calcium antagonist (40 mg twice a day) or ace-inhibitor (25 mg twice a day) treatment which continued for 180 days. Monotherapy was combined with hydrochlorothiazide (12.5 mg/day) after 2 months in the event of an unsatisfactory reduction of arterial pressure in relation to basal values. Systolic and diastolic blood pressure was measured (1st and 5th Korotkoff's tone) at monthly intervals while lying and standing; heart rate was also measured using a palpatory method. Both nicardipine retard (no. 86) and captopril (no. 88) caused a significant reduction of clino- and orthostatic systolic and diastolic arterial pressure during the first two months of treatment. Respectively 70% and 51% of patients responded to treatment and the blood pressure reductions achieved using monotherapy remained unchanged during the course of the study. The association of hydrochlorothiazide resulted in a significant decrease in arterial pressure in non-responders, an effect which was observed with both nicardipine retard and captopril. No significant variation in heart rate was recorded between the two groups. Twenty-one patients in the nicardipine retard group and 16 in the captopril group suffered from slight to moderate side effects. Six patients dropped out of the nicardipine retard group and 15 patients out of the captopril group, an event for which side-effects were responsible in 1 and 3 cases respectively. In conclusion, nicardipine retard and captopril represent an efficacious form of treatment for geriatric hypertension and possess a satisfactory level of tolerability. PMID- 1461545 TI - [Efficacy of L-thyroxine (L-T4) therapy on the volume of the thyroid gland and nodules in patients with euthyroid nodular goiter (ENG)]. AB - The efficacy of treatment with TSH suppressive doses of L-thyroxine was evaluated by echography in 35 patients with euthyroid nodular goiter. Patients have been subdivided in two groups comparable for sex age and size of the goiter. Sixteen patients were treated for nine months with suppressive doses of thyroxine and nineteen were followed without therapy as control. Patients in treatment were then followed up for additional 9 months without therapy. The mean decrease of thyroid volume at nine months was 25% (27 +/- 10 ml vs 20 +/- 8 ml; p < 0.01). After discontinuation of treatment thyroid volume increased and had returned to base line values after nine months of follow up. In the control group mean thyroid volume had increased by 17.7% at nine months (28 +/- 17 vs 33 +/- 19 ml; p < 0.001). Thyroid nodules in response to thyroid hormone treatment showed a variable behaviour: 30.7% (4/13) of the nodules responded to the therapy with a reduction > to 25% at the ninth month; the remaining nodules were insensitive to the therapy. In conclusion suppressive thyroxine treatment is effective in reducing the goiter, nodules instead are only in part sensitive to the treatment. Thyroxine therapy of euthyroid nodular goiter must be followed for long term since upon thyroxine discontinuation there is a prompt reappearance of the goiter. PMID- 1461546 TI - [Imaging diagnosis, echography and CAT in mechanical jaundice]. AB - In a review of 70 cases of extra-hepatic cholestasis of different origin, the great diagnostic value of imaging techniques, echography and computed tomography, was demonstrated in distinguishing the type of jaundice, and in defining the cause and site of obstruction. PMID- 1461547 TI - [Homologous artificial insemination: current perspectives]. PMID- 1461548 TI - [High resolution electrophoresis of serum aand amniotic fluid]. AB - In a sample group of 92 women undergoing prenatal echo-guided transabdominal amniocentesis between the 12th and 23rd week of pregnancy the Authors analysed amniotic fluid and maternal serum using the recently developed method of high resolution protein electrophoresis in order to identify the presence of particular proteins in the amniotic fluid which are pathognomonic for a number of maternofetal pathologies. The results obtained in normal and pathological pregnancies or in the case of twins showed a marked dispersion in amniotic fluid of total protein concentrations depending on the period of gestation; in addition, albumin, alpha 1-antitrypsin, alpha 2-glycoprotein acid, alpha 2 macroglobulin and beta 2-protein were also found. Plasma levels of prealbumin, albumin, alpha 1-glycoprotein acid and IgG were slightly reduced, whereas there was a marked increase in ceruloplasmin, transferrin and fibrinogen; C3 and haptoglobin levels were normal. It is therefore possible to ascertain that amniotic fluid proteins analysed by high-resolution 15-band electrophoresis did not vary qualitatively or quantitatively until the 23rd week of gestation and in those cases of twin or pathological pregnancies examined no anomalous band was found in the protein electrophoresis of maternal serum or amniotic fluid which might prove useful in prenatal diagnosis. PMID- 1461549 TI - [Evaluation of a new method for cervical cytology]. AB - An adequate sample is the most important factor for successful cervical cytology. In this study a conventional method is compared to a new method of biopsy in a group of 40 patients undergoing tests in June 1991. A quantitative and qualitative evaluation of esocervical and endocervical cells was made; similar percentages were obtained for floor cells using both using systems, whereas higher percentage values (82.5% vs 67.5%) were obtained for cylindrical cells using the new method. Compared to the conventional method the new method also possessed an inadequacy rate of below 50% in post-menopausal patients. Therefore, although the new method is similar to the conventional one in terms of quality, it is thought to be more appropriate due to the greater number of endocervical cells collected, especially in post-menopausal patients. PMID- 1461550 TI - [Decisional analysis in the diagnosis of Chlamydia trachomatis]. AB - The aim of this work is the use of decisional analysis for the clinical diagnosis of Chlamydia trachomatis, to verify the utility of making a routine direct immunofluorescence test with a strategy of no routine direct immunofluorescence test with a strategy of no routine test in women during gynecologic escannations. Patients eligible for this analysis were sexually active woman, who are not pregnant, woman in reproductive age who do not have evidence of a clinical syndrome associated with or known to be caused by Chlamydia trachomatis. Our results show that the decision as to the use of the test involves 0.87 utility, while the decision of no routine test involves a 0.80 utility. We can therefore deduce that the best strategy for a woman who subjects herself to routine gynecologic care is to use this test, because the Chlamydia trachomatis has been implicated as the etiologic agent of acute salpingitis, chronic and tubal infertility. PMID- 1461551 TI - [Screening of endometrial carcinoma]. AB - The Authors analyse the characteristics of the carcinoma of the endometrium concluding that this neoplasia has the necessary requirements to undergo a screening by means of endometrial cytology. The Authors believe that this test should be combined with those carried out to prevent cervical and mammary neoplasia, applying a total screening to the gynaecological neoplasia. PMID- 1461552 TI - [Treatment of premenstrual syndrome. Experience and considerations]. AB - The Authors review the scientific literature on premenstrual syndrome (PMS), focusing on the diagnostic standards and the complex symptomatologic pattern. They report, furthermore, the results of a study of 4 groups of patients affected by PMS and treated with different therapeutic programs. The data obtained confirm that treatment of PMS must be personal and valued on the ground of dominant group of symptoms. PMID- 1461553 TI - [Evaluation of the efficacy and tolerability of nimesulide in the treatment of mastodynia]. AB - In a double blind clinical trial 40 female patients, aged between 14 and 65 years, affected by mastodynia associated with benign non neoplastic disease of the breast, underwent oral treatment with nimesulide (200 mg/day) or placebo for a period of 15 consecutive days, during which no other drug therapy was assumed. The administration of nimesulide produced a clinically significant attenuation of mammary tenseness and mastodynia, in most cases up to complete remission of the symptoms. No adverse reaction was observed. PMID- 1461555 TI - [Treatment of dysfunctional metrorrhagia with GnRH analogs]. AB - Thirty patients diagnosed as affected by dysfunctional metrorrhagia were treated with goserelin in a registered formulation of 3.6 mg injected subcutaneously into the anterior abdominal wall. These patients suffered from hypochromic anemia secondary to metrorrhagia with asthenic symptoms. After six months' treatment there was a significant improvement in hemocrasia and symptoms resolved without collateral effects requiring the suspension of treatment. The 10 patients who subsequently underwent surgery were in excellent condition and did not require blood transfusions. PMID- 1461554 TI - [Pain control during the expulsion period in labor using bupivacaine and fentanyl]. AB - The association of extremely diluted concentrations of opioids and local anesthetics appears to be highly promising for pain control during labour. This study examined the efficacy of the association of Fentanyl 100 mcg and Bupivacaine 10 mg in second-stage labour pain and perineal pain. The study which was carried out in 20 patients confirmed the lack of collateral effects on the fetus, mother (except for slight itching in 25% of cases) and the progress of labour. A virtually total elimination of pain was obtained in all cases during the dilatation and expulsion stages. During the second stage of labour pain was completely abolished in 50% of cases, whereas in the remaining 50% it lasted on average for 13 minutes. Perineal analgesia was sufficient to allow episiorrhaphy in 50% of patients without resorting to the use of local anesthetic. PMID- 1461556 TI - [Sexuality of the aging male]. AB - The paper discusses data reported in the literature concerning the sexual behaviour of elderly males and examines the role played by anatomical alterations to the genital tract, erection physiology and psycho-physical performance. The Authors review the current possibilities of treatment for sexual therapy in elderly males. PMID- 1461557 TI - [Research on the understanding of the relation between patient, gynecologist and breast disease]. AB - The aim of our work was to identify the most important aspects of the relationship between gynecologist and patient who presents himself during our observation because of breast pathology. In order to evaluate all that said above we asked patients to compile a questionnaire characterized by different questions. The results obtained were very satisfactory and at the same time they lead us to a greater engagement towards the prevention of breast neoplasia, especially for those women predisposed to such disease. PMID- 1461558 TI - [HELLP syndrome. Discussion of a case]. AB - The HELLP syndrome is the most severe variant of pre-eclampsia. A case is reported in a primigravida patient at 25 weeks of gestation. The lack of response to medical treatment and the deterioration of maternal indices necessitated a Cesarean section with intensive neonatal care at a very premature stage. The physiopathological grounds and the various methods of treating this syndrome are discussed and the paper concludes that rapid birth is the only solution capable of preventing severe maternal complications. PMID- 1461559 TI - [Mondor syndrome. Etiopathogenesis and case report]. AB - The Authors observed and report a case of Mondor's syndrome in a male. In the attempt to identify the real origin in this peculiar thrombophlebitis they reviewed the recent literature. It is apparently impossible to drawn definitive conclusions from the different studies on this subject. Anyway Mondor's syndrome looks suitable for inclusion in the group of jumping thrombophlebitis. Therefore the real cause of the venous accident should be a pathologic situation next to the venous branch where the thrombophlebitis has broken out. PMID- 1461560 TI - 1S,3R-ACPD-sensitive (metabotropic) [3H]glutamate receptor binding in membranes. AB - Metabotropic glutamate receptors are selectively activated by 1S,3R-1 aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). [3H]Glutamate binding sites in rat brain membranes were characterized in the presence of (RS)-alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-D aspartate (NMDA) to block binding to ionotropic glutamate receptors. 1S,3R-ACPD displaced a single population of [3H]glutamate binding sites and was mimicked by other metabotropic glutamate agonists with a potency order of L-glutamate > 1S,3R ACPD > ibotenate > 1R,3S-ACPD. Quisqualate interacted at two populations of binding sites. 1S,3R-ACPD-sensitive [3H]glutamate binding was saturable (Bmax = 2.50 +/- 0.27 pmol/mg protein), reversible, and had high-affinity (KD = 187 +/- 60 nM). 1S,3R-ACPD-sensitive [3H]glutamate binding likely represents labeling of metabotropic glutamate receptors in rat brain membranes. PMID- 1461561 TI - Alteration of delta-6 desaturase by vitamin E in rat brain and liver. AB - delta-6 Desaturase, measured at substrate saturation using linoleic acid, was found to be increased by more than two-fold when the content of vitamin E in brain microsomal membrane suspension was increased (up to 7.5 micrograms/mg membrane protein, i.e. 100 micrograms/g tissue from which microsomes were prepared). In contrast, this activity was reduced by 25% in the liver. This raises the question of the multiple role of vitamin E in membranes, the control of membrane polyunsaturated fatty acids through synthesis, and their protection against peroxidation. PMID- 1461562 TI - Rhythmic activities in the rat solitary complex in vitro. AB - In adult rat brainstem slices, rhythmic discharge of action potentials occurred spontaneously in 10 out of 197 cells of the solitary complex. In 6 neurones, fast rhythms (2-6 per min) were characterized by volleys of synaptic activity presenting abrupt onset denoting synchronized discharge of presynaptic elements. Synchronizing signals may be generated by cells discharging bursts of high frequency action potentials and presenting extensive axonal arborization, as observed in one cell. Slower rhythms (0.3-0.8 per min) monitored in three cells did not involve synchronizing processes and could be evoked in non-rhythmic cells by 15-30 min bath application of the cholecystokinin octapeptide (100 nM). These results suggest distinct operating mechanisms of fast and slow rhythms in the solitary complex in vitro. PMID- 1461563 TI - The effect of halothane on cultured fibroblasts and neuroblastoma cells. AB - Halothane exposure over the cultured cells (100 and 1,000 ppm) caused a disruption of the pattern of actin distribution in both fibroblasts and neuroblastoma cells. Neuroblastoma cells exposed to halothane also lost microspikes; however, neurite elongation was not affected by halothane. The present study suggests that halothane induces the functional disruption of actin, resulting in an interference of normal neural development in vivo. PMID- 1461564 TI - Mutations in genes for acetylcholinesterase intensify lethality by acrylamide in Caenorhabditis elegans. AB - Acrylamide inhibits growth and results in death in the nematode Caenorhabditis elegans. The lethargic effect is marked in the mutants defective in genes for acetylcholinesterase (AChE) and the effect is approximately parallel with the decrease in AChE activity by mutations. Although neither the activity nor the localization of the enzyme is affected by acrylamide, the acetylcholine level was significantly elevated. PMID- 1461565 TI - Activation of D1 receptors stimulates accumulation of gamma-aminobutyric acid in slices of the pars reticulata of 6-hydroxydopamine-lesioned rats. AB - D1 dopamine receptors are present on terminals of striatal neurons to the pars reticulata of the substantia nigra in the rat. Here we have studied the effect of the activation of these receptors on the synthesis of gamma-aminobutyric acid (GABA) in slices of the pars reticulata of the substantia nigra isolated from 6 hydroxydopamine-lesioned rats. The synthesis was judged by the accumulation of GABA after inhibiting GABA transaminase with aminooxyacetic acid. Both dopamine and SCH 23390, a D1 agonist, stimulated the synthesis. The effect of both compounds was blocked by SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. In the absence of receptor activation, the synthesis was very slow. The results suggest a trophic influence of dopamine upon the synthesis of GABA via D1 receptors. PMID- 1461566 TI - Formation of muscle spindles in the absence of motor innervation. AB - Whether muscle spindles can form in muscles innervated only by afferents was investigated by removing the lumbosacral segment of the spinal cord immediately after crushing the nerve to the medial gastrocnemius (MG) muscle in newborn rats, and administering nerve growth factor for 10 days afterwards. The nerve-crushed MG muscles reinnervated by afferents in the absence of motor innervation were examined at postnatal (P) days 7, 9 and 30 for the presence of spindles by light and electron microscope. Reinnervated MG muscles contained spindle-like encapsulations of 1-4 fibers at 7, 9 and 30 days after the nerve crush. The number of spindles exceeded that of normal MG muscles, suggestive of de novo formation of spindles. All nerve-muscle contacts in the spindles had features of sensory endings, and intrafusal fibers expressed the spindle-specific slow-tonic myosin heavy chain (MHC) isoform at P30. No motor endplates were visible on any muscle fibers and extrafusal fibers were atrophied, as would be predicted in the absence of motor innervation. Thus, efferents are not essential for the formation and differentiation of muscle spindles in reinnervated muscles of neonatal rats. PMID- 1461567 TI - Serotonin modulates auditory information processing in the cochlear nucleus of the rat. AB - The effect of iontophoretic application of serotonin (5-HT) was studied in neurons of the cochlear nucleus in the rat. 5-HT inhibited the spontaneous activity in 71%, and the tone-evoked activity in 32% of the neurons. We also observed an excitatory effect, with a longer latency than that of the inhibition, in 40% of the neurons. In some neurons 5-HT had both inhibitory and excitatory effects. Neurons with different response types seem to have different sensitivities to 5-HT. As the effects of 5-HT were generally weaker than those of other putative neurotransmitters, it probably has only a small modulatory influence on auditory processing. PMID- 1461568 TI - Pattern of electroencephalographic activity during light induced seizures in genetic epileptic chicken and brain chimeras. AB - Genetic epilepsy was studied in Fayoumi epileptic (F.Epi) chickens and in neural chimeras obtained by selective substitution of embryonic brain vesicles of F.Epi donors in normal recipient chickens. Typical motor seizures accompanied by convulsions were evoked by intermittent light stimulation in F.Epi and in chimeras having embryonic substitution of the prosencephalon and the mesencephalon. The motor seizure was less severe in chimeras receiving only the prosencephalon. In the F.Epi, as well as in all the chimeras, the EEG during seizures was characterized by a desynchronized (or a flattening) pattern of activity. F.Epi and chimeras had a lower threshold to Metrazol induced seizures than control chickens. The experimental animals show that, in this model, large prosencephalic and mesencephalic areas are involved in the epileptic disease. The epileptic character of this genetic dysfunction is discussed. PMID- 1461569 TI - Ricinus communis agglutinin I reacting and non-reacting butyrylcholinesterase in human cerebrospinal fluid. AB - Differences in glycosylation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in human brain, plasma and cerebrospinal fluid (CSF) have been investigated by means of their interaction with agarose immobilized lectins. Most of the AChE in brain and CSF was associated to concanavalin A (Con A), Lens culinaris (LCA) and Triticum vulgaris (WGA) agglutinins, but little activity was adsorbed to Ricinus communis agglutinin I (RCAI). Brain, plasma and CSF BuChE was almost fully bound to Con A, LCA and WGA agarose. Brain BuChE was unable to react with RCA (RCA-BuChE), the plasma enzyme was completely bound to the lectin (RCA+BuChE) and BuChE from CSF of normal children was partially fixed to RCA (RCA +/- BuChE). BuChE in CSF of children with meningitis fully reacts with the lectin. The data suggest that the proportion of RCA+BuChE in CSF of children with meningitis is increased, this enzyme probably coming from plasma. PMID- 1461570 TI - Cross-linking of 125I-alpha-bungarotoxin to Drosophila head membranes identifies a 42 kDa toxin binding polypeptide. AB - The nicotinic acetylcholine receptor (nAChR) antagonist alpha-bungarotoxin (alpha Btx) binds to two different classes of high affinity binding sites from the Drosophila central nervous system. We have used the bivalent reagent 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide (EDAC) to cross-link 125I-alpha-Btx (M(r) = 8 kDa) to Drosophila head membranes. Upon sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), one major adduct of M(r) approximately 50 kDa was identified, suggesting that a 42 kDa polypeptide binds the toxin. Adduct formation was inhibited by other cholinergic ligands. Detergent-solubilized receptor complexes containing the cross-linked products were immunoprecipitated by antisera against two nAChR subunits previously identified by molecular cloning, the ALS and ARD proteins, suggesting that the 42 kDa toxin binding polypeptide constitutes a component of the previously described class 1 alpha-Btx binding site. PMID- 1461571 TI - A neuroprotective effect of adenosine A1-receptor agonists on ischemia-induced decrease in 2-deoxyglucose uptake in rat hippocampal slices. AB - The effects of adenosine (A) receptor agonists on ischemia-induced impairment of 2-deoxyglucose (2-DG) uptake by rat hippocampal slices was evaluated. Hippocampal slices were exposed to 20-min hypoxia + hypoglycemia (ischemia) and then returned to oxygenated and glucose-containing Krebs-Ringer solution for 6 h. Ischemia reduced 2-DG uptake in the hippocampal slices. The ischemia-induced reduction in 2-DG uptake was attenuated by pretreatment with A1 receptor agonists but not with A2 receptor agonists. 8-Phenyltheophylline, an A1 receptor antagonist, exacerbated the ischemia-induced decrease. The A1 receptor agonist-induced neuroprotective effect was blocked by co-treatment with 8-phenyltheophylline. The present study suggests that the A1 receptor-mediated function has a protective role in ischemia-induced decreases in glucose metabolism in hippocampal slices. PMID- 1461572 TI - Postnatal development of neuropeptide Y-containing neurons in the visual cortex of normal- and dark-reared rats. AB - The postnatal development of neuropeptide Y (NPY)-immunoreactive neurons in the visual cortical areas (17, 18 and 18a) has been studied in Wistar rats reared under normal lighting conditions or in complete darkness. Immunohistochemistry on paraffin sections at postnatal days (P)7, 14, 21, 30 and 60 showed an overall similarity in laminar distribution of NPY neurons in all 3 visual areas of both normal- and dark-reared animals. The pattern of development of NPY neurons was characterized by an increase in their density from P7 to reach a peak at P21 followed by a decline to 37-47% of peak levels at P60. However, this diminution was not so great in dark-reared rats as in the normal, since the density only decreased to 62-78% of peak levels. At P60 the resulting differences in neuron density were marked in areas 17 and 18, where the dark-reared had 75% more cells than normal, and moderate in area 18a (30% more than normal). These results suggest that the normal decline in NPY neurons is not entirely mediated by visual experience since it takes place, albeit to a modified extent, in its total absence. PMID- 1461573 TI - Presence of functional vasopressin V1 receptors in rat vagal afferent neurones. AB - The nucleus of the solitary tract (NTS) is one of the brain regions by which arginine vasopressin (AVP) influences blood pressure. This series of experiments in adult male rats was designed to determine whether the AVP binding sites which have been demonstrated in the NTS by in vitro autoradiography might be presynaptic on vagal afferents from the nodose ganglion; whether the AVP binding sites on vagal afferent neurones are functional receptors; and whether vagal transport of AVP receptors to other organs also occurs. High affinity binding sites (using the selective V1 antagonist radioligand [125I][d(CH2)5,Sar7]AVP and in vitro autoradiography) with characteristics of V1 receptors in the medial subnucleus of the NTS were reduced by 40% ipsilateral to nodose ganglionectomy. The nodose ganglion itself also contained high affinity V1 AVP binding sites that localised over cell bodies of vagal sensory neurones. That these binding sites were functional receptors was apparent when low concentrations of AVP but not oxytocin were found to depolarize the isolated nodose ganglion utilizing the 'silicone grease gap' technique. Furthermore, the actions of AVP were antagonised by low concentrations of a selective V1 receptor antagonist. However, there was no accumulation of AVP binding sites adjacent to either the proximal or distal vagal ligations suggesting that peripheral vagal transport of AVP receptors may not occur. Therefore these results are consistent with functional AVP V1 receptors occurring in the nodose ganglion. These receptors may occur on central terminals of vagal sensory neurones in the medial subnucleus of the NTS, but there was no evidence for peripheral transport of AVP V1 receptors. PMID- 1461574 TI - Effects of lipopolysaccharide on food-motivated behavior in the rat are not blocked by an interleukin-1 receptor antagonist. AB - To investigate the role of interleukin-1 (IL-1) in the decrease in food-motivated behavior after peripheral administration of lipopolysaccharide (LPS), rats trained to press a lever for food on a fixed ratio 10 schedule were pre-treated with a recombinant human IL-1 receptor antagonist (IL-1ra). This endogenous cytokine has been shown to block most of the inflammatory and immune effects of IL-1 both in vitro and in vivo. Intraperitoneal (i.p.) injection of LPS (400 micrograms/kg) decreased operant responding for food to 30-60% of baseline for 1 4 h. Response rates gradually recovered, but were still below control levels 8 and 24 h post-injection. Neither i.p. (8 mg/kg) nor intracerebroventricular (288 micrograms/kg) administration of IL-1ra blocked the effects of peripherally administered LPS on food-motivated behavior. These results suggest that the effects of LPS on this behavior are not mediated by the release of IL-1. PMID- 1461575 TI - Expression of c-fos protein in lumbosacral spinal cord in response to vaginocervical stimulation in rats. AB - The pattern of vaginocervical stimulation-evoked expression of the proto-oncogene c-fos in lumbar 5-sacral 1 segments of the spinal cord of ovariectomized adult rats was mapped using immunocytochemistry. A calibrated force of mechanostimulation was applied to the vaginal cervix of experimental animals and to the perineum of control animals while they were gently restrained. The number of cells expressing c-fos was significantly greater in the experimental than the control animals in laminae I, IV, V-VI and X. The implications of the present findings for elucidating the spinal pathways mediating the various behavioral, neuroendocrine and autonomic effects of vaginocervical stimulation (VS) are discussed. PMID- 1461577 TI - MSNJ and the PRO. PMID- 1461576 TI - AIDS. PMID- 1461578 TI - National Mental Health Month. PMID- 1461579 TI - The importance of cancer registries. PMID- 1461580 TI - Review article: venous thromboembolism in trauma patients. AB - The increased coagulability in multiple injured patients results in increased risk for deep venous thrombosis and pulmonary embolism. The authors discuss etiology, diagnosis, treatment, and prophylaxis of venous thromboembolism in trauma patients. PMID- 1461581 TI - Omeprazole in the treatment of peptic ulcers and gastroesophageal reflux disease. AB - Omeprazole blocks the final step of gastric acid secretion by blocking the proton pump (the hydrogen and potassium ATPase) in gastric parietal cells. Due to this direct action, omeprazole is the most potent, clinically available suppressor of gastric acidity. PMID- 1461582 TI - General surgery: is there a future? AB - General surgery may not survive in an age of superspecialization unless the emphasis of general surgical training shifts from broad competence to defined areas of expertise. The author presents suggestions for restructuring general surgery residency requirements. PMID- 1461583 TI - Completeness of case ascertainment of the State Cancer Registry. AB - The authors evaluated the ability of the New Jersey State Cancer Registry to detect known cancer cases during an investigation of a cancer cluster occurring in professional football players. The Registry was found to be a valuable tool for the detection of cancer cases for New Jersey residents. PMID- 1461584 TI - The New Jersey health care delivery structure--a clarification. AB - Recent SBME rules were developed from issues raised by a previous commissioner of health. SBME received comments on these issues at two public hearings. SBME drafted the rules to incorporate the substance and the principles of the state's Health Care Cost Reduction Act. PMID- 1461586 TI - 1992-1993 MSNJ councils and committees. PMID- 1461585 TI - CLIA-88 final rule: Part 2. AB - Physicians performing moderate or high complexity tests will need to prepare their office laboratories to meet CLIA-88 government standards. Doctors who have not applied for their registration certificate should do so immediately. This is the second in a three-part series. PMID- 1461587 TI - Children's preferences for high-fat foods. AB - Many high-fat foods are highly preferred by adults, and children soon acquire these preferences. The circumstances and mechanisms that contribute to establishing children's preferences for high-fat foods are the subject of this review. PMID- 1461588 TI - Some effects of deep frying on dietary fat intake. PMID- 1461589 TI - Body weight, fat storage, and alcohol metabolism. AB - Ethanol account for a significant fraction of the energy intake of persons consuming even moderate amounts of alcohol. A recent study has shown that although alcohol does not reveal itself as a layer floating at the top of a drink, metabolically it behaves more like oil than sugar. PMID- 1461590 TI - Retinoids and carotenoids as inhibitors of carcinogenesis and inducers of cell cell communication. AB - In cell cultures of carcinogen-initiated fibroblasts, a number of retinoids and carotenoids can reversibly inhibit progression to the transformed state. The anticarcinogenic action of retinoids and carotenoids is closely correlated with enhanced gap-junction cell-to-cell communication and with increased synthesis of the gap-junction protein, connexin. PMID- 1461591 TI - Directional coronary atherectomy in lesions unfavourable for balloon angioplasty: initial Green Lane and Mercy Hospitals experience. AB - AIMS: directional coronary atherectomy is a new percutaneous interventional technique in which coronary arterial stenotic material is shaved off to alleviate stenosis. This study presents the initial outcome of coronary atherectomy at Green Lane and Mercy hospitals where the major indications for atherectomy are lesions with angiographic appearances unfavourable for balloon angioplasty or where balloon angioplasty had been unsuccessful. METHODS: data on patients undergoing coronary atherectomy between February 1990 and December 1991 were analysed. No patient or procedure was excluded. RESULTS: for the first 28 lesions in 25 patients, procedural success, improvement in lumen diameter to less than 50% diameter loss stenosis, but freedom from myocardial infarction, death or emergency bypass surgery, was achieved in 27 of 28 lesions. In one patient there was acute thrombotic coronary arterial closure treated successfully by balloon angioplasty. Another patient developed an asymptomatic fistulous connection with an adjacent coronary vein which resolved spontaneously. CONCLUSIONS: although technically more difficult than balloon angioplasty, directional coronary atherectomy can be carried out in selected patients with a high initial success rate and low complication rate. The technique has allowed percutaneous treatment of a number of selected patients unsuitable for balloon angioplasty, and has turned an unsuccessful angioplasty into an initial procedural success in others. PMID- 1461592 TI - Pneumococcal bacteraemia in south Auckland: a five year review with emphasis on prescribing practices. AB - AIMS: to determine incidence, predisposing factors, management and outcome of pneumococcal bacteraemia in south Auckland. METHODS: medical records were reviewed retrospectively of patients identified as having pneumococcal bacteraemia at Middlemore Hospital during five years 1986-90. RESULTS: records were available for 143 of 149 episodes. The incidence of pneumococcal bacteraemia was 12.1/10,000 admissions. The male to female ratio was 1.2:1, 61.5% were over the age of 50 years, 76% had underlying medical conditions, and the mortality was 16.1%. Twenty of the 23 who died were over the age of 60 years. Just over half attended hospital within 48 hours of becoming unwell, while 10.5% had had symptoms for more than one week. Pneumonia was seen in 85% and meningitis in 7%. Initial treatment was with a single antibiotic in 94%. Following microbiological diagnosis, 54% were treated with penicillin G, but in over one-third, an unnecessarily broad spectrum antibiotic was continued as definitive treatment. CONCLUSIONS: the incidence, age distribution, predisposing factors and mortality of pneumococcal bacteraemia in south Auckland is similar to those reported elsewhere. Inappropriately broad spectrum antibiotics are used too often in definitive treatment. PMID- 1461593 TI - Electrolyte intake and the prevention of hypertension. PMID- 1461594 TI - Adolescence and sun protection. AB - AIM: to examine adolescents' sun behaviours and use of sun protection measures, attitudes to tanning, and awareness of melanoma, in the light of the Cancer Society's Sun-smart campaign in the summer of 1990-1. METHODS: a sample of 345 fourth formers from schools in Auckland, Wellington and Christchurch was surveyed regarding their experiences and beliefs about tanning, and their use of sun protection measures including sunblock lotions, hats and clothing; their knowledge of melanoma and risks for melanoma; and their exposure to the educational campaign and its message. RESULTS: despite relatively high awareness of melanoma as a dangerous form of cancer, a significant proportion of the sample showed high positive attitudes towards tanning and high levels of sun exposure without adequate sun protection. On the positive side, reports of exposure to sources of information about melanoma were correlated with melanoma awareness, which in turn predicted use of sun protection measures. CONCLUSION: the findings suggest that campaigns such as those of the Cancer Society have an important role to play in reducing high levels of sun exposure among adolescents. Continued efforts need to be directed at adolescents to increase the acceptability and use of sun protection measures. PMID- 1461595 TI - General practitioners' views on the role of the community pharmacist. AB - AIM: to determine the views of general practitioners on the roles and activities of community pharmacists. METHOD: the views of 137 general practitioners in Otago and Southland were canvassed by postal questionnaire. RESULTS: one hundred and three completed questionnaires were returned. All of the general practitioners reported that their professional contact with pharmacists was useful. Seventy five percent expressed a desire for greater cooperation. Nearly all respondents (99%) accepted that pharmacists have a role in screening prescriptions for possible problems and preparing and dispensing medicines. They also accepted that pharmacists were capable of treating and advising in the management of minor illnesses. Providing drug information to general practitioners, information about previously diagnosed conditions to patients, and advice on personal and home hygiene were less widely accepted activities. The majority indicated that they considered it inappropriate for pharmacists to undertake screening programmes (blood pressure (70.6%), cholesterol (70.6%), glucose (60.8%), haemoglobin (72.5%)). Younger general practitioners objected more often than older general practitioners to reclassification of Acetopt eye drops from prescription only to availability through pharmacies (p < 0.05). Female general practitioners were more often in favour of reclassification of Gyno-Daktarin than their male colleagues (p < 0.05). CONCLUSION: this study shows that general practitioners accept several aspects of the current role of pharmacists in providing primary health care. However, there is room for improved communication between general practitioners and pharmacists to ensure optimum patient care. PMID- 1461596 TI - Medical ethics and the New World Order. PMID- 1461597 TI - Industrial disaster planning. PMID- 1461598 TI - Screening for noninsulin dependent diabetes mellitus and impaired glucose tolerance. PMID- 1461599 TI - Matching or selection bias in the fenoterol studies? PMID- 1461600 TI - Fenoterol: enough is enough. PMID- 1461602 TI - Professional conduct? PMID- 1461601 TI - Glottic laryngeal cancer in New Zealand. PMID- 1461603 TI - Traumatic birth. PMID- 1461604 TI - Age and ethnicity as prognostic factors influencing overall survival in breast cancer patients in the Auckland region. Auckland Breast Cancer Study Group. AB - AIMS: to assess the effect of age at diagnosis and ethnicity on overall survival from breast cancer. METHODS: information was collected from 2706 breast cancer patients in the Auckland region, diagnosed between 1976 and 1985. Age at diagnosis was categorised into four groups: < 35 years, 35-49 years, 50-74 years and 75 years or older. Ethnicity was self reported in three categories: European, Maori and Pacific Island Polynesian. Independent effects were assessed by controlling for extent of disease, specifically metastases at presentation, nodal status and size of tumour. RESULTS: age and ethnic group were both significantly related to overall survival in univariate analyses. In multivariate analysis, age had an independent effect on survival mainly due to a significant survival difference between women aged less than 35 years and those aged 35 to 49 years (p < 0.0001; RR = 2.02). Survival was not significantly different between other age groups when adjustments were made for extent of disease. There was no significant effect of ethnicity on survival in the reduced dataset used for the multivariate analysis. Separate analyses suggested that ethnic differences in the extent of disease at diagnosis may be the cause of the apparent initial effect of ethnicity on survival. CONCLUSIONS: women < 35 years at diagnosis have a significantly poorer prognosis than women aged 35-49 years. Other differences between age groups were not significant when stage of disease was taken into account. Ethnicity was not an independent factor influencing survival after controlling for extent of disease but numbers in the Maori and Pacific Island groups were too small to conclusively evaluate any effect of ethnic group on prognosis. PMID- 1461605 TI - Membranous nephropathy: a 19 year prospective study in 51 patients. AB - AIM: to study prospectively patients presenting with membranous nephropathy. METHODS: the outcome of 51 patients (33 male; mean age 50.8 SD 17.7 years; 49 caucasian, two Maori), aged 14 years and over, with membranous nephropathy was studied prospectively. The patients were enrolled between 1 July 1972 and 30 June 1991. Patients with systemic lupus erythematosus were excluded. Membranous nephropathy was secondary to drug therapy in eight (gold 3, nonsteroidal antiinflammatory drug 3, penicillamine 1, captopril 1). All patients were hepatitis B surface antigen negative. The majority of patients did not receive immunosuppressive therapy. RESULTS: forty-seven (92%) presented with the nephrotic syndrome, eight (16%) with a plasma creatinine > or = 0.15 mmol/L and 28 (55%) with hypertension. The patients were followed for a mean of 5.4 years, the median being 3.9 years and range four months-19 years. The 10 year cumulative renal survival was estimated to be 78% and overall survival 66%. Six patients have entered a renal replacement programme and six have died of nonrenal causes. Of the remaining 39, eight have renal insufficiency, 27 hypertension and 22 proteinuria. Complete remission occurred in 17 (33%)-11 spontaneously, four following withdrawal of the offending drug and two after immunosuppressive therapy. Poor prognostic indicators at presentation included renal insufficiency, need for antihypertensive therapy, pathological stage IV on renal biopsy and older age. CONCLUSIONS: membranous nephropathy is an indolent disease with a good chance of spontaneous remission. In most patients immunosuppressive treatment appears unwarranted. PMID- 1461606 TI - When important social interests compete with privacy. PMID- 1461607 TI - Attitudes to specialist recertification: results of a national survey among pathologists. AB - AIMS: to evaluate attitudes and preferred mechanisms in the establishment of specialist recertification for pathologists. METHODS: a national survey was conducted amongst the membership of the New Zealand Society of Pathologists. RESULTS: responses were received from 54 (62%) financial members of the society. The majority of respondents agreed with the concept of compulsory periodic recertification. The ideal recertification period should be 10 years and the system should be supervised by the New Zealand Society of Pathologists. The favoured recertification mechanism was by continuing medical education which should be funded by the individual candidate. The majority of respondents supported the establishment of voluntary recertification on a trial basis. CONCLUSIONS: the survey suggested a favourable attribute amongst pathologists to the introduction of continuing education based periodic recertification. PMID- 1461608 TI - Health screening in a general practice by opportunistic recruitment. AB - AIMS: this study aims to assess the effectiveness of opportunistic recruitment into a general practice health screening programme and subsequent improvement in screening rates. METHODS: a study group of 754 patients aged 30-69 years (345 men, 409 women) in a Wanganui general practice were invited by the doctor when attending the surgery to return for a preventive health check. The check included a self administered screening questionnaire, selected examination items performed by the practice nurse, and a consultation with the doctor to review the findings. RESULTS: over the three year study period 327 of the men and 392 of the women attended the surgery. An invitation to return for a health check was offered to 307 men and 329 women with completion of health checks by 294 men and 317 women, resulting in a screening rate in the study group of 85% for men and 78% for women. Selected screening indicators showed improvement with blood pressure recording increasing from 48% to 85% for men, and cervical cancer screening improving from 45% to 87% for women. CONCLUSION: opportunistic recruitment by the doctor's personal invitation proved an effective approach to health screening in this practice with significant improvement in selected screening indicators. PMID- 1461609 TI - Which cephalosporin? PMID- 1461610 TI - Commercially sensitive ethics. PMID- 1461611 TI - Medical ethics. PMID- 1461612 TI - Occupational overuse syndrome. PMID- 1461613 TI - Health expenditure and health reforms. PMID- 1461614 TI - Health expenditure and health reforms. PMID- 1461615 TI - Health reforms. PMID- 1461616 TI - ASH and marijuana. PMID- 1461617 TI - Blood products and hepatitis C. PMID- 1461618 TI - Health reforms. PMID- 1461619 TI - Overview of hormonal therapy in advanced breast cancer. PMID- 1461620 TI - Potential applications of high-dose megestrol acetate in breast cancer. AB - Empiric clinical trials have revealed new mechanisms by which hormonal therapies may exert their antitumor effects. Initial studies using escalated doses of agents like toremifene and megestrol acetate have yielded interesting results, showing responses in hormone-receptor-negative patients and in patients progressing after standard doses, respectively. A trial by Cancer and Leukemia Group B randomizing patients with advanced breast cancer to standard-dose (160 mg) megestrol acetate or to 5 or 10 times the standard dose (800 and 1,600 mg) has completed accrual. It is hoped that these results will provide a definitive answer to the dose-response issue for breast cancer. However, regardless of this trial's ultimate outcome, higher doses of megestrol acetate have demonstrated important new effects on appetite stimulation and weight gain; ongoing laboratory research promises potential roles for megestrol acetate in the reversal of chemotherapeutic drug-induced tumor resistance. PMID- 1461621 TI - Current controversies in the endocrine therapy of advanced breast cancer. AB - The response of breast cancer to endocrine therapy depends on depriving the tumor cells of estrogen stimulation of cell division. This may be achieved by blocking estrogen synthesis in the body, using inhibitors of aromatase or by using drugs like tamoxifen, which interfere with the direct effects of estrogen on tumor cells. Current controversies relate to the mechanism for achieving more effective inhibition of estrogen synthesis and for the use of more specific antiestrogenic drugs. PMID- 1461622 TI - Megestrol acetate in the treatment of metastatic carcinoma of the prostate. AB - Although current hormonal therapy of prostate cancer may not appear to have altered survival appreciably, there have been considerable changes that may significantly affect the future management of this disease. A number of new hormonal agents have been introduced that still require definition of their therapeutic efficacy. Megestrol acetate, a hormonal agent with multiple sites of action in androgen metabolism, has recently been investigated in the treatment of patients with metastatic and locally advanced disease, and in those patients whose disease progresses with other hormonal therapies. Megestrol acetate plus mini-dose diethylstilbestrol (DES) is associated with fewer side effects than standard-dose DES and has equivalent therapeutic efficacy in the treatment of patients with metastatic disease. In patients with locally advanced disease that may benefit from hormonal cytoreduction, megestrol acetate is effective and well tolerated. Megestrol acetate has a role in the palliation of patients with progressive disease despite initial hormonal therapy. Considerable controversy surrounds the therapy of carcinoma of the prostate; further studies are required to define optimal hormonal therapy. PMID- 1461623 TI - Pathophysiology of cancer: hormonal and metabolic abnormalities. AB - Despite the development of advanced nutritional support technology, malnutrition remains a significant morbid and mortal complication of cancer. A number of metabolic abnormalities have been demonstrated in malnourished cancer patients, including increased protein breakdown, increased glucose production, increased lipolysis, hypogonadism in male patients, and insulin resistance. Previous studies conducted under metabolic ward conditions have demonstrated that metabolic abnormalities interfere with efforts at renutrition of patients with localized head and neck cancer. Efforts to correct these abnormalities by treatment with hydrazine sulfate, anabolic androgens, and insulinotropic drugs have been ineffective. An improved understanding of the pathophysiology of cancer malnutrition may lead to improved therapies of this vexing clinical problem. PMID- 1461624 TI - Clinical aspects of nutrition in advanced cancer. AB - Nutritional assessments of our patients with disseminated malignancies have revealed that the incidences of reported anorexia, decreased food intake, and weight loss range between 49 and 64%. It is therefore essential that a planned approach to the nutritional needs of patients with advanced cancer be part of routine oncology care. Our first step is a clinical assessment of the patient's nutritional state and diet, and a determination of caloric and nutrient needs. The potential tools available to the oncologist in the management of the undernourished cancer patient are many and include dietary counseling, food supplements (which contain vitamins and other micronutrients), stimulation of appetite, enteral nutrition, total parenteral nutrition, or a combination of these. The dietitian can be an invaluable component of the cancer care team, both in the inpatient and outpatient settings. An understanding of the role of each intervention will enable the physician to use available resources rationally and efficiently. PMID- 1461625 TI - Treatment of cancer weight loss in patients with advanced lung cancer. AB - Megestrol acetate, a semisynthetic gestagen, is effective not only for endocrine therapy of advanced breast carcinomas, but also in the treatment of cachectic patients with aggressive, hormone-independent tumors. Sixty-six patients with therapy-resistant, advanced bronchogenic carcinomas of different histologic types, who had lost more than 10% of their regular body weight within a prospective, randomized trial, were treated with megestrol acetate at a dose of either 160 or 480 mg/day for 3-4 months. The mean weight gain for all patients was 2.5 kg. Nearly all of them (80%) reported improved appetite and well-being. The mean weight gain in the group of patients receiving 480 mg/day was higher (3.0 kg) than in the group receiving 160 mg/day (2.0 kg). PMID- 1461626 TI - Clinical management of anorexia and cachexia in patients with advanced cancer. AB - Cachexia occurs in the majority of cancer patients before death. It is the result of major metabolic changes produced by tumor-released substances as well as by cytokines and some endogenous peptides. The most significant clinical manifestation is profound anorexia. Aggressive parenteral nutrition has not been able to increase patient survival or produce any significant symptomatic improvement. Recent research, therefore, has focused on drugs that might result in symptomatic improvement, even if no significant nutritional changes are detected. Corticosteroids have been shown to increase appetite for a brief period of time, but they do not appear to improve caloric intake or nutritional status. In addition to appetite stimulation, corticosteroids also improve a number of other symptoms transiently. Progestational drugs have been found in a number of studies to increase appetite, caloric intake, and nutritional status. The most effective type and dose of progestational drugs have not been clearly established. Cyproheptadine, hydrazine sulfate, and cannabinoids have all been suggested to have beneficial effects on appetite; their effectiveness, however, needs to be confirmed in prospective, controlled trials. Some of these trials are currently under way. Current data suggest that megestrol acetate or other progestational agents could be useful--because of effects on not only appetite but also overall nutritional status--in patients who have profound anorexia as the main manifestation of cachexia, provided expected survival can be measured in weeks or months. In patients with shorter expected survival or those who have problems tolerating progestational drugs, a brief course of corticosteroids may provide short-term symptomatic effects. Future studies should focus on (1) improving understanding of both the pathophysiology of cancer cachexia and the interaction of some of the major syndromes of terminal cancer--e.g., pain, cachexia, and cognitive failure--and (2) characterizing the symptomatic effects of different drugs more completely. PMID- 1461627 TI - Risks and benefits of various therapies for cancer anorexia. AB - A placebo-controlled, randomized trial assessed the activity, tolerance, and degree of weight gain and anorexia of two doses of megestrol acetate in patients with advanced cancer and cachexia. Patients received either low-dose (480 mg/day) or high-dose (960 mg/day) megestrol acetate or placebo for 8 weeks. As of March 1991, 91 patients had been randomized; 65 patients were evaluable. Median initial weight loss in all patients ranged from 13 to 16%. Further weight loss was seen in 13 of 17 patients in the placebo group, compared with 10 of 27 and 6 of 21 in the low- and high-dose megestrol acetate groups, respectively. Eight of 27 patients in the low-dose-group and 9 of 21 in the high-dose group gained weight, with a median of 3 and 4 kg, respectively. Beneficial effects of megestrol acetate were seen in 63 and 71% of the low- and high-dose groups, respectively, compared with 24% of the placebo group. Side effects of megestrol acetate were mild. No correlation between megestrol acetate dosage and weight gain was found, but there was a tendency for increased weight in more patients taking high-dose megestrol acetate. PMID- 1461628 TI - Megestrol acetate for anorexia and cachexia. AB - Based on promising preliminary information obtained from uncontrolled pilot studies, several randomized, placebo-controlled, double-blind clinical trials have been launched to evaluate the effectiveness of megestrol acetate for the treatment of patients with anorexia and/or cachexia. The results of these studies have demonstrated that megestrol acetate can improve patients' appetites and promote nonfluid weight gain in some. They also suggest that megestrol acetate has antiemetic properties. Ongoing clinical trials are evaluating the dose response relationship of megestrol acetate for these clinical problems and whether megestrol acetate will improve the survival of patients at risk for developing cancer anorexia/cachexia. PMID- 1461629 TI - HIV-related cachexia: potential mechanisms and treatment. AB - Involuntary weight loss or wasting indicative of severe protein energy malnutrition is a frequent complication of acquired immune deficiency syndrome (AIDS). Malnutrition, with its associated adverse effects on immunocompetence, may contribute to the progression of AIDS itself. Since death from wasting is ultimately related to the magnitude of tissue depletion, restoration of body cell mass may enhance survival. The mechanism of weight loss in AIDS has not been clearly elucidated. The etiology is likely to be multifactorial, the result of interactions between decreased caloric intake, malabsorption, and alterations in energy expenditure secondary to hormonal and/or metabolic abnormalities. Although weight loss is occasionally reversible with treatment of underlying infections and/or easily identifiable and reversible causes, the majority of patients are not this fortunate. Enteral and parenteral nutrition, which are expensive, cumbersome, and potentially morbid, have been suggested by some as therapeutic options. Megestrol acetate, a synthetic, orally active progestational agent, has been reported to stimulate appetite and weight gain. Data regarding the use of megestrol acetate for the treatment of cachexia related to human immunodeficiency virus (HIV) infection demonstrate convincingly its effectiveness in treating many patients with HIV-related anorexia and cachexia. PMID- 1461630 TI - High-dose megestrol acetate as third-line endocrine therapy for metastatic breast cancer. AB - High-dose megestrol acetate (800 mg/day) was administered to 34 patients as third line endocrine therapy for metastatic breast cancer after progression on standard dose megestrol acetate (160 mg/day). Among the 32 evaluable patients, no complete or partial response occurred. Ten patients remained stable and 22 progressed. No patients remained on study. Median time to progression was 2 months (range, 1-13 months). The use of high-dose megestrol acetate did not result in objective responses but may have been effective in delaying progression in one third of patients. PMID- 1461631 TI - [The expression of the apolipoprotein A-1 gene in the early stages of human embryogenesis studied by hybridization in situ]. AB - The apolipoprotein A-1 (apo A-1) gene expression at certain stages of human embryo development was studied using an in situ hybridization procedure. By the fifth week of development, the presence of apo A-1 mRNAs was detected in cells of different tissue types such as CNS rudiment, somite myotomes, ear vesicle, nasal placodes, lens, apical areas of the maxillary, mandibular and hyoid arcs, mesenchyme of limb buds, small intestine, mesonephros, genital ridge, and several types of blood cells. At later stages (weeks 8-9) the distribution of these mRNAs showed considerable changes. The high apo A-1 mRNA level was characteristic of liver cells, adrenals, kidney, neural tube and ganglia. These data suggest that changes in tissue-specific apo A-1 gene expression during human embryogenesis may be associated with the development of blood circulatory system and CNS. PMID- 1461632 TI - [An immunohistochemical analysis of rat hippocampal antigens in early postnatal ontogeny by using monoclonal antibodies]. AB - In order to study the molecular mechanisms of neurogenesis, monoclonal antibodies (MAbs) were produced against antigens of the developing rat hippocampus. MAb 3G7 F8 was used for immunohistochemical localization of the corresponding antigen of paraffin sections of the rat brain at days 0, 5, 14, and 21 of the postnatal development. In the hippocampus of newborn and 5-day-old rats, positive immunostaining was observed in the cytoplasm and proximal segments of processes of neurons located in granular, polymorph, and pyramidal layers, as well as in entorhinal cortex. In granule cell bodies and neurons of entorhinal cortex specific staining decreased by day 14 and disappeared by day 21 after birth, whereas neurons of pyramidal and polymorph layers remained immunopositive. Diffuse specific staining in the cerebellum was observed beginning from day 5 after birth in the Purkinje cell layer. On days 14-21 positive reaction was observed in Purkinje cell bodies and in the layer containing dendrites of Purkinje cells and parallel fibers. External and internal granular layers remained immunonegative. No specific staining was observed in other regions of the brain, as well as in the control slices. These data suggest that the antigen detected by the 3G7-F8 antibody is involved in the formation of the neuronal connections. PMID- 1461633 TI - [Contractile proteins and nonerythroid spectrin in the oogenesis of the clawed toad]. AB - Distribution of contractile proteins, actin and myosin, and spectrin was studied in oogenesis of X. laevis. These proteins are present already at the previtellogenic stages, where they are diffusely distributed. During vitellogenesis actin and myosin are distributed in the animal region in a fibril like way, while in the vegetal one they are concentrated around the yolk platelets. In the mature oocyte, distribution of actin and myosin again becomes diffuse. Spectrin forms in the vitellogenic oocyte a network all over the cytoplasm, while in the full-grown oocyte it is localized mostly in the subcortex of the animal region and disappears during oocyte maturation. All these proteins are present in the nuclei of oocytes. Changes in distribution of actin, myosin and spectrin during oocyte maturation are discussed with reference to the cortical contractility, spatial distribution of yolk platelets and regional sensitivity to cytochalasin B. PMID- 1461634 TI - [The nuclei of follicular cells do not control oocyte maturation in amphibians induced by gonadotropic hormones in vitro]. AB - The inhibitory effect of actinomycin D (5 micrograms/ml) on maturation of the follicle-enclosed oocytes of Rana temporaria and Xenopus laevis induced in vitro by pituitary suspension and human chorionic gonadotropin, respectively, is not observed at low concentrations of the hormones. These data suggest that nuclei of the follicle cells are not involved in the control of the pituitary-dependent oocyte maturation in amphibians. PMID- 1461635 TI - [The population kinetics of human male germ cells in the antenatal period of ontogeny]. AB - Time course of development of male germ cells in man during prenatal development was studied quantitatively for the first time. For each period of the prenatal development the following characteristics were determined: relationship between the number of germ and somatic cells in spermatic cords, mitotic index for germ cells the intensity of their degeneration, average diameter of their nuclei, and the proportion of germ cells at the stage of preleptothene. PMID- 1461636 TI - [The dermatoglyphic analysis of polydactyly and the segregation of the morphogenetic fields of the fingers in man]. AB - We studied dermatoglyphic imprints of patients with preaxial or postaxial polydactyly. Development of the additional finger is shown to be always accompanied by the corresponding finger triradius and basic line; postaxial polydactylies are characterized by the circular epidermal ridges around the rudiment of the sixth finger and the presence of the second additional triradius. On the basis of these data we suggest that major lines of the palm and finger triradii serve as landmarks denoting the borders of individual morphogenetic fields of fingers during their segregation from general morphogenetic field of the hand which is related to the polar system of coordinates. PMID- 1461637 TI - [Intracerebral transplants of embryonic nerve tissue result in the recovery of the ultrastructure of dystrophic neurons following hypoxia in adult rats]. AB - Fragments of the intact rat embryonic brain cortex were transplanted into sensomotor cortex of adult Wistar rats subjected to hypoxia 26 days before surgery. Ultrastructure of the host brain was studied 4, 100, 130 days, 1.5, and 2 years after the operation using electron microscopy. The observed regeneration of ultrastructure of the host's neurons appears to be due to either recovery or de novo formation of the organelles. PMID- 1461638 TI - [The three-dimensional structure of the tunica intima and tunica media of the human fetal aorta studied by a new method]. AB - A new method is developed for revealing the latent surfaces in the structure of organs by scanning electronic microscopy. The method is based on the treatment of specimens with potassium ethoxide until cells start to appear in the dissociating solution. Using this method, thoracic aorta of nine human fetuses at the stage of 20-28 weeks was studied. Subendothelial intima and media of human fetal aorta contain smooth muscle cells differing by their arrangement, shape and surface microrelief. The intima cells are arranged in a mosaic pattern formed of single cells or cell clusters. By means of cell processes they are connected with each other, as well as with endothelial and smooth muscle cells of the media. Smooth muscle cells in the inner part of the media also have processes and form an open network. Part of the cells penetrate the intima through pores of the inner elastic membrane. In the deeper layers of the media, laterally adjoining spindle shaped smooth muscle cells are found. It is suggested that the observed cell polymorphism is due mostly to penetration of the media smooth muscle cells into subendothelium and modification of their shape under the effect of the microenvironment. PMID- 1461639 TI - [Alcohol and the liver: ethanol metabolism and the pathomechanism of alcoholic liver damage]. AB - Ethanol is oxidized in the liver by three different enzyme systems, namely by alcohol dehidrogenase (ADH), the microsomal ethanol oxidizing system and catalase. Alcohol also undergoes a first pass metabolism in the gastric mucosa due to alcohol dehydrogenase. This first pass metabolism of ethanol is decreased in the alcoholic, in the fasted state, in the elderly and during cimetidine therapy leading to elevated alcohol blood-concentrations. Ethanol toxicity is closely related to its metabolism in the liver. Ethanol oxidation by ADH generates reducing equivalents (NADH) and acetaldehyde (AA). The elevated NADH/NAD ratio results in alterations of the intermediary metabolism of lipids, carbohydrates, proteins, purines, hormones and porphyrins. Furthermore, NADH flavours free radical production. The ethanol-associated redox changes are pronounced in the perivenular zone, since this is the area of low oxygen tension and of high ADH activity. In addition to NADH, AA exerts striking toxic effects on the hepatocyte. AA binds to cellular proteins and membranes including the mitochondria, microtubules, glutathion and various enzymes. In addition, AA and lactate stimulate collagen production in fibroblasts. AA-adducts stimulate the production of antibodies against AA-epitopes and could thus aggravate the liver injury. Chronic ethanol consumption results also in the microsomal induction of a specific ethanol-inducible form of cytochrome P--450, the cytochrome P--450IIE1 with high affinity not only to ethanol but also to some drugs (acetaminophen), procarcinogens (nitrosamines) and industrial agents (carbon tetrachloride). The interaction between ethanol metabolism and the metabolism of these compounds including vitamin A may also contribute to hepatic toxicity, since the susceptibility of the alcoholic toward those compounds is enhanced. PMID- 1461640 TI - [Significance of determination of squamous cell carcinoma antigen in the follow up of patients with cancer of the uterine cervix]. AB - The serum concentrations of squamous cell carcinoma antigen (SCC) were determined in 59 patients with invasive carcinoma of the uterine cervix, in 21 patients with benign cervical diseases. Pretherapeutic SCC levels were elevated (> 2.5 ng/ml) in 63% (34/54) of the patients with squamous cervical carcinoma. 5 patients with adenomatosus cervical carcinoma had not elevated levels. In 21 patients with benign cervical diseases, 4.8% (1/21) of SCC values were above the normal range. There were no correlation of SCC levels and the degree of the histological differentiation or clinical stages. Serial SCC determinations revealed a correlation with the clinical course of disease in 72.2% (26/36) with squamous cervical carcinoma. Rising levels were always associated with progression. The SCC level increased before clinical signs of progression with a median lead time of 3 months. Patients with cervical adenocarcinoma for follow up CA 125 determination was recommended. The determination of SCC is a useful tool checking the patients, detecting early progression of squamous cervical tumor. PMID- 1461641 TI - [False positive results of exercise tests with thallium myocardial scintigraphy]. AB - The authors have examined supposed causes of positive Th-201 stress scintigraphy. Patients were divided into two groups according to the presence of exercise induced transitory hypoperfusion or in absence of it. In both groups negative coronarograms were verified. Results of two groups were compared according to parameters of the left ventricle function, pulmonary pressure, to the presence of disorder of system stimulus-conduction (LBBB, RBBB), mitral prolapsus, foramen ovale apertum, anomalous coronary anatomy, level of load during exercise, body weight, heart volume-index. Significant difference was found in disorder of left ventricle motion, ejection fraction and in comprehensive value of left ventricle function (F1). PMID- 1461642 TI - [Incidence of intrauterine growth retardation and its significance in perinatology in Hungary]. AB - The authors have examined the incidence of intrauterine growth retardation at a country level for the first time both in local and international aspect. Using the nomenclature of NDN-system they have found the frequency of WL-(proportional) retardation 7.95% and that of N-(disproportional) retardation 5.99%. They show incidence of retardation from county to county, as well. Examining the correlation between retardation and perinatal mortality they've stated that while the frequency of still-birth among the average developed and proportionally nutrified fetus is 0.34% and the frequency of perinatal mortality among them is 1.23%, that of the N-retardated newborns is 0.88% and 2.08%, respectively, and that of the WL-retarded is higher than the latter: 2.03% and 3.90% respectively. Regarding the incidence and mortality ratio among the two types of retardation the difference is significant. PMID- 1461643 TI - [Pancreatic cystic tumor misdiagnosed as pseudocyst: lessons from an intraoperative error]. AB - A 62-year old woman presented a fistula due to a previously made cystojejunostomy performed because of a small pancreatic lesion considered as a pseudocyst. This intervention was performed in another institute. In the course of the exploration the authors resected the whole mass with the Roux-en-Y loop, and with the spleen. The histological examination proved a cystadenocarcinoma of the pancreas. There are discussed the problems of the intraoperative diagnosis of pancreatic lesions, and the possibilities of the reduction of mistakes. The authors emphasize the experience of the surgeon--which is the most important factor of the cure--and the importance of the fine needle biopsy. PMID- 1461644 TI - [A 150-year old controversy on occupational health issues]. PMID- 1461645 TI - [Our predecessors on venous diseases]. PMID- 1461646 TI - Proviral insertions near cyclin D1 in mouse lymphomas: a parallel for BCL1 translocations in human B-cell neoplasms. AB - By isolating genomic DNA clones that encompass the mouse Cyl-1 (cyclin D1) locus, we have identified a putative CpG island close to the 5' end of the gene. Pulsed field gel electrophoresis with probes derived from either the 5' or 3' side of the CpG island established physical linkage to two independent markers on mouse chromosome 7, in a region that is syntenic with human chromosome 11q13. On the 3' side, Cyl-1 is approximately 75 kb from Hst-1 and Int-2, although there is an additional CpG island in the intervening DNA, while on the 5' side, Cyl-1 is less than 300 kb from Fis-1, an integration site for Friend murine leukaemia virus. As there is no intervening CpG island, proviral insertions at Fis-1 could influence the expression of Cyl-1 and we describe two virally induced tumours in which this appears to be the case. The data suggest that proviral insertions near Cyl-1 in mouse lymphomas are functionally equivalent to the BCL1 translocations that activate cyclin D1 expression in human B-cell malignancies. PMID- 1461647 TI - T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes. AB - Two members of the RBTN gene family, RBTN1/Ttg-1 and RBTN2/Ttg-2, were found by their association with T-cell tumour-specific chromosomal translocations and are thought to be involved in the aetiology of such T-cell tumours. Here a transgenic mouse model is described in which T-cell tumours are induced by the presence of RBTN1 and RBTN2 transgenes that direct expression in thymus-derived cells. The latency period for lymphoid tumour appearance is variable, and tumours occur in a small proportion of transgenic animals that develop T-cell acute lymphoblastic malignancies. No significant increase in the rate of tumour development was observed in RBTN1 transgenic mice infected with Moloney murine leukaemia virus, nor did tumours arise in mice bearing a construct in which RBTN1 was expressed from the insulin transcriptional promoter. These data, which provide formal proof of the oncogenic activity of these genes, suggest that aberrant expression of transcription factor genes, such as RBTN1 and RBTN2, functions in tumour aetiology by disturbing some aspect of T-cell differentiation. PMID- 1461648 TI - Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes. AB - The human T-cell leukemia virus type 1 (HTLV-I) is associated with adult CD4+ T cell leukemia (ATL) and tropical spastic paraparesis (TSP). In as much as only a small percentage of individuals infected with HTLV-I develop either disease, we set out to model a genetic partner for this virus in an effort to understand and possibly reproduce its pathophysiology. To this end we have developed a binary set of transgenic mice, one bearing the relatively inactive HTLV-I long terminal repeat (LTR) positioned to drive the c-myc oncogene and another bearing a fusion transgene consisting of the immunoglobulin promoter/enhancer driving the gene for the HTLV-I transcription activator, tax. Alone, the tax construct, though expressed in the thymus, spleen, lung and brain, has no deleterious effect. Alone, the HTLV-I LTR/c-myc construct is expressed at very low levels in lymphoid cells and occasionally induces lymphomas in older animals. When these two transgenic lines are mated, bigenic offspring harboring both transgenes exhibit dramatic tumor formation. As in the human, these animals develop CD4+ T-cell lymphomas, but they also develop central nervous system tumors by 25-90 days of age. The syndrome, which is 100% penetrant and lethal, provides an animal model for adult T-cell lymphoma and a source of cultured cells of neurogenic origin. PMID- 1461649 TI - A novel NF-kappa B element within exon 1 of the murine c-myc gene. AB - We have mapped a site within exon 1 of the murine c-myc gene that forms a variety of complexes with nuclear proteins derived from the murine WEHI 231 B-lymphoma cell line in exponential growth that are altered following treatment with phorbol ester, when transcription of this gene is reduced [Levine, R.A., McCormack, J.E., Buckler, A.J. & Sonenshein, G.E. (1986). Mol. Cell Biol., 6, 4112-4116]. This site, located at +440 to +459 bp relative to the P1 promoter, contains an NK kappa B-like binding element. The sequence of this element, AGGGAATTTTT, is unusual in that the stretch of pyrimidines is entirely T residues. Binding of NF kappa B protein was demonstrated by oligonucleotide competition, induction of binding upon 70Z/3 pre-B- to B-cell differentiation, response to GTP in the binding reaction, reduction of binding upon addition of I kappa B protein and uv cross-linking analysis. Functional activity of this internal regulatory element (IRE) was demonstrated in transfection assays using chloramphenicol acetyl transferase (CAT) reporter constructs containing multimerized copies of the IRE driving a heterologous promoter. Mutation of the IRE within the context of the c myc promoter prevented NF-kappa B-mediated induction of transcription of this oncogene. Thus additional NF-kappa B elements may be defined by this new sequence. PMID- 1461650 TI - c-myc and p53 gene expression in the differentiation of temperature-sensitive mutants of teratocarcinoma F9 cells. AB - We have previously reported the isolation of several temperature-sensitive (ts) mutants of F9 cells. Further investigations showed that some mutants were induced to differentiate at non-permissive temperature of cell growth, accompanied by changes in the expression of various genes, whereas others were not. During the differentiation induced by shifting up to the non-permissive temperature, a rapid and transient decrease in both c-myc and p53 mRNA levels and rapid induction of c jun mRNA were observed. These changes were specific in differentiation-inducible mutants and were not observed in a non-inducible mutant. In both types of mutants, the level of c-myc mRNA decreased in association with growth retardation at the non-permissive temperature. The p53 mRNA, however, showed specific increase in the differentiation-inducible ts mutants. These observations suggest distinct roles for p53 and c-myc from proliferation to differentiation in teratocarcinoma stem cells. PMID- 1461651 TI - Molecular characterization and structural organization of D-elg, an ets proto oncogene-related gene of Drosophila. AB - We have continued the molecular analysis of D-elg, a member of the Drosophila ets gene family. Based on the characterization of cDNA and genomic sequences, the D elg gene contains five exons and four introns and produces a mRNA with an open reading frame of 464 amino acids. Consistent with this analysis, in vitro translation of a near full-length D-elg cRNA yields a protein with a molecular weight of approximately 56 kDa. D-elg shows significant homology to other ets proteins in the amino-terminal A domain and strong homology in the carboxy terminal ETS domain. The D-elg protein is most similar to the alpha-subunit of the mouse GA-binding protein. PMID- 1461652 TI - Characterization of activated and normal mouse Mos gene in murine 3T3 cells. AB - We have characterized the mouse Mos proto-oncogene product, pp39Mos, in murine fibroblasts. When expressed in NIH3T3 cells under the influence of the long terminal repeat regulatory element from Moloney murine sarcoma virus [NIH(pTS-1) cells], the Mos protein was present in low levels and had a half-life of about 30 min. In extracts from NIH(pTS-1) cells, we detected additional forms of Mos protein that apparently arose from internal initiation codons (p24Mos and p29Mos) or from upstream non-AUG initiation codons (p42Mos and p44Mos). The Mos protein was found to exist in these cells as a phosphoprotein, pp39Mos, and, when immunoprecipitated with an antiserum specific for the Mos N-terminus [anti-Mos(6 24)], had autophosphorylating kinase activity. We found that anti-Mos(6-24) also detected non-Mos protein kinase activity and non-Mos phosphoproteins in addition to p39Mos. We present evidence, on both the RNA and protein levels, that non transformed mouse 3T3 cells do not express endogenous Mos. PMID- 1461653 TI - Increased expression of the negative growth factor, galactoside-binding protein, gene in transformed thyroid cells and in human thyroid carcinomas. AB - Murine beta-galactoside-binding protein has been shown to be a cell growth regulatory molecule and a cytostatic factor. We analysed the beta-galactoside binding protein gene expression in a thyroid cell system including two normal cell lines (FRTL-5 and PC Cl 3) and the same cells transfected by several oncogenes that induce different degrees of malignancy and differentiation. We show that beta-galactoside-binding protein mRNA levels correlate with the expression of the malignant phenotype. Run-on experiments suggest that a transcriptional effect accounts at least in part for such a difference. We also show that the beta-galactoside-binding protein gene expression is increased in most human papillary thyroid carcinomas compared with normal thyroid. PMID- 1461654 TI - DNA amplification at 11q13.5-q14 in human breast cancer. AB - Band q13 of chromosome 11 is frequently amplified in human breast cancers, but the gene(s) responsible for the emergence of this amplicon remain(s) elusive as yet. As a tribute to the complexity of the amplification events involving 11q13 sequences in human breast cancer, we have now studied a more telomeric region at 11q13.5-q14 defined by a new transcription unit, D11S833E. We have observed that amplicons present in cell lines and primary tumors amplified for both BCL1 and D11S833E could be interrupted between these two loci. Such discontinuities were demonstrated by using a probe for the KRN1 gene, which we have localized between the BCL1/FGF4 region and D11S833E. In fact, KRN1 was not present in 4 out of 10 amplicons bearing both BCL1 and D11S833E. Furthermore, we have observed tumors in which D11S833E could be amplified in the absence of amplification of other known markers of 11q13. Therefore, D11S833E defines a new and independent amplification unit in this region. PMID- 1461656 TI - Inactivation of the murine N-ras gene by gene targeting. AB - The mammalian ras genes have been implicated in the genesis of a wide variety of tumors. Although it is likely that they play an essential role in signal transduction, their specific function is still unknown. To initiate a genetic analysis of the ras genes in mammals we inactivated the N-ras gene in murine embryonic stem cells by gene targeting. The frequency of integration at the N-ras locus of our targeting vector being low (of the order of 1/5000 transfectants), we used a positive/negative selection followed by an analysis of individual colonies in order to minimize the in vitro manipulation of the embryonic stem cells. Using this approach, we isolated two clones of ES cells with one inactivated N-ras allele. These cells have no distinctive phenotype either in vitro or in vivo in chimeric mice. PMID- 1461655 TI - Rearrangement of the human tre oncogene by homologous recombination between Alu repeats of nucleotide sequences from two different chromosomes. AB - The rearranged region of the tre oncogene originating from chromosomes 5q23q31 and 18q12 was cloned from tumor genomic DNA, sequenced and aligned with wild-type sequences cloned from a normal human genomic library. In the breakpoint region each wild-type sequence contained two Alu repeats. The recombination occurred between the 3'-most Alu from chromosome 5 and the 5'-most Alu from chromosome 18 and, consequently, resulted in a hybrid Alu flanked with one Alu on either side. The recombinant joint was located to a 20-bp homology region in left arms of the Alu repeats involved in recombination. The same homology region was identified in the hybrid Alu of the rearranged tre. At its 5' extremity the homology region overlaps the B box of Alu-borne RNA polymerase III promoter. The 100% identity score in the region of homology suggests that the recombination process was conservative and not error prone. PMID- 1461657 TI - Alternative splicing in the human lck gene leads to the deletion of exon 1' and results in a new type II lck transcript. AB - In this study we describe a new lck mRNA transcribed from the type II promoter, resulting from alternative splicing, in the deletion of exon 1' which comprises the AUG initiation codon. In this type IIB lck transcript, as a consequence of exon 1' deletion, a new AUG codon in exon 1, located 35 nt upstream from the regular initiation codon in exon 1', and normally out of frame, is now in frame with exon 2 and the following lck coding sequence. In this type IIB lck transcript, 10 residues encoded by exon 1 from the new AUG codon replace the first 35 residues encoded by exon 1'. Strikingly, in this new N-terminal amino acid sequence, a glycine residue, needed for myristylation and anchorage in the plasma membrane, is present at position 2. This alternative splicing has been observed in T-cell lines, normal mature T cells and in peripheral blood lymphocytes from different leukemic patients. Different ratios of regular type IIA lck mRNA (with exon 1') to spliced type IIB lck mRNA (without exon 1') have been observed depending on the patient. PMID- 1461658 TI - p53 and RAS gene mutations in multiple myeloma. AB - We analysed genomic DNA from 30 patients with multiple myeloma (MM), searching for alterations in the p53 and RAS genes by a combination of polymerase chain reaction and single-strand conformation polymorphism techniques. Mutations in the p53 gene were observed in 20% (6 out of 30) of the patients, and were located in conserved sequence blocks within exons 5 and 7. These were single-nucleotide substitutions and consisted predominantly (4/6) of G:C to A:T transitions. Of the six patients with a mutated p53 gene, four were in the terminal phase of the disease. RAS gene mutations were found more frequently since they occurred in 47% (14 out of 30) of the patients. Mutations consisted of single-nucleotide substitutions, located in codons 12, 13 and 61 of either K- or N-RAS, to the exclusion of H-RAS. Moreover, one patient bore two simultaneous mutations, affecting simultaneously the K- and the N-RAS genes. RAS gene mutations were more frequently observed in patients with fulminating disease (10/15, 67%) than in patients with less aggressive forms of the disease (4/15, 26%). We also analysed genomic DNAs from 10 human myeloma cell lines, of which two bore mutations affecting codon 12 of the K-RAS gene, and one codon 12 of the N-RAS gene. The first two cell lines were obtained from freshly explanted tumor cells in which we observed identical mutations. Results presented here show that activating mutations in the RAS genes are, in MM, more frequent than those affecting the p53 gene and suggest that both events are related to terminal phases of the disease. PMID- 1461659 TI - The amino acid sequence of a mammalian MAP kinase kinase. AB - The amino acid sequence of the dual specificity mitogen-activated protein kinase kinase (MAPKK) has been determined by cDNA cloning and amino acid sequencing. MAPKK (393 residues, Mr 43,330) is a new member of the protein kinase subclass that comprises byr1 and STE7 that are involved in pheromone dependent signal transduction in yeast, wis1 a mitotic regulator in S. pombe and PBS2, which confers antibiotic resistance in S. cerevisiae. PMID- 1461661 TI - Health care reform: California reform plan blends strengths. PMID- 1461660 TI - Growing old affects understanding KePRO. PMID- 1461662 TI - Society to recognize physicians involved in their communities. PMID- 1461663 TI - Looking for changes in retroactive HCFA directives. PMID- 1461664 TI - Trends in staff compensation. PMID- 1461665 TI - The anterior cruciate ligament-deficient knee: a diagnostic and therapeutic algorithm. AB - The anterior cruciate ligament (ACL) of the knee is a common site of sports related injury. The natural history of chronic instability, reinjury, and further intra-articular damage is well documented. Appropriate management of ACL insufficiency must be based upon a knowledge of the available diagnostic and therapeutic options, their indications, and their effectiveness. At the same time, the treatment plan must be tailored to the demands and expectations of the individual patient. PMID- 1461666 TI - Meniscal tears: diagnosis, evaluation, and treatment. AB - Arthroscopic surgery for treatment of pathologic meniscal lesions has become the most commonly performed orthopaedic procedure in the United States. This article reviews the diagnosis, evaluation, and subsequent treatment of meniscal tears in the knee. PMID- 1461667 TI - Myositis ossificans traumatica. AB - Myositis ossificans is a benign condition of heterotopic bone formation. It is a generalized term for four separate clinical entities. Although not a rare disease process, diagnosis often remains difficult. This article reviews the various forms of myositis ossificans, as well as the pathology, diagnostic tests, and treatment options. PMID- 1461668 TI - New outpatient treatment of recurrent patellar dislocations. AB - From December 1987 through February 1991, outpatient arthroscopic procedures were done on patients experiencing recurrent dislocations of the patella. A modified Emslie-Trillat procedure was used. Twenty-four patients (27 knees) were available for follow-up. Using the criteria of Cox, excellent results were found in 78% (21 knees), whereas 18% (5 knees) were rated as good. Only 4% (1 knee) was considered fair, and none were rated poor. Most patients (96%) showed improvement. No patient suffered a postoperative dislocation. Based upon the findings of this study, it is concluded that this procedure is an effective method of treatment for patients having recurrent dislocations of the patella. PMID- 1461669 TI - Difficult reductions in traumatic patellar dislocation. AB - A traumatic lateral dislocation with internal rotation of the patella can be unreducible using conventional maneuvers. These unusual dislocations may involve locking of the patella on the lateral femoral condyle. In these cases, reduction can be achieved by applying a downward force to the lateral aspect of the patella, which reduces the rotational deformity and unlocks the medial patellar facet. PMID- 1461670 TI - Brachial plexus injury with erect dislocation of the shoulder. AB - Luxatio erecta, or inferior dislocation of the glenohumeral joint, is an extremely uncommon variety of shoulder dislocation. Several types of neurovascular injuries may be associated with luxatio erecta. Concomitant fracture of the coracoid, clavicle, acromion, greater tuberosity, and humeral head may also be noted. A case of luxatio erecta associated with a fracture of the greater tuberosity and transient mixed brachial plexus injuries is presented. PMID- 1461671 TI - A unicompartmental knee replacement is not "half a total knee": five major differences. AB - Unicompartmental knee replacement surgery has known uneven success. It fell out of favor in the late 1970s as it was gradually replaced by total knee arthroplasty. The failures of unicompartmental replacements were due partly to the implants themselves but largely to incomplete knowledge of the principles and techniques associated with the unicompartmental knee replacement procedure. As newer implants become available, it is easy to focus on the technology at the expense of basic principles. The authors elaborate on five key principles that differentiate unicompartmental knee replacement from total knee arthroplasty. PMID- 1461672 TI - A 22-year-old man with a swollen left hand after a motor vehicle accident. AB - The following case is presented to illustrate roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon and emergency room physician. The initial history, physical examination, and pertinent roentgenographic findings are found on this page. The final clinical diagnosis is presented on the next page. PMID- 1461673 TI - Meniscal tears. PMID- 1461674 TI - Prescribing NSAIDs. PMID- 1461675 TI - Cytotoxic activity of 13-hydroxyoctadecadienoic acid against Toxoplasma gondii. AB - Recent data indicate that platelets may play an important role in the host defence against Toxoplasma gondii infections. T. gondii-stimulated human platelets release thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid (12 HETE) from arachidonic acid and 13-hydroxyoctadecadienoic acid (13-HODE) from linoleic acid (Yong et al. 1991; Henderson et al. 1992). We have previously demonstrated that the eicosanoid TXA2 has potent cytotoxic activity against T. gondii trophozoites (Yong et al. 1991). In this study, we examined whether 12 HETE, 13-HODE, and linoleic acid also have toxoplasmacidal activity. 13-HODE at concentrations > or = 10(-8) M rapidly induced cytotoxic changes in T. gondii. Ultrastructural changes induced by 13-HODE in T. gondii included an initial leakage of cytoplasmic contents into a space between the inner and outer parasite bilayer membrane units which was followed by intracellular vacuolation and loss of cytoplasmic contents. In contrast, linoleic acid and 12-HETE lacked toxoplasmacidal activity at 10(-10)-10(-6) M concentrations. These data indicate that 13-HODE, a product of linoleic acid metabolism, has potent cytotoxic activity against T. gondii; this toxoplasmacidal activity may be important in the inflammatory response to this pathogen. PMID- 1461676 TI - Plasmodium berghei and Plasmodium chabaudi chabaudi: development of simple in vitro erythrocyte invasion assays. AB - Erythrocyte invasion assays are described for two species of rodent malaria, namely Plasmodium berghei and P.c. chabaudi. These invasion assays are simple, are carried out using a candle jar and allow a number of assays to be performed simultaneously. Our results demonstrate that both rodent malaria species show an in vitro preference for reticulocytes although the preference of P. c. chabaudi for these cells is not as marked as that of P. berghei. The details of our invasion assays and our results obtained are discussed. PMID- 1461677 TI - Assessment of parasite population dynamics in mixed infections of rodent plasmodia. AB - Cloned lines of the four rodent Plasmodium species can be differentiated by the RFLP pattern generated following Southern blotting and probing with PCsv4.1, a probe derived from a P. chabaudi chabaudi genomic library. Groups of CBA/Ca mice were inoculated simultaneously with cloned lines from two parasite species or strains. Six mixed species and three mixed strain infections using rodent malaria lines were initiated. The composition of the parasite population in each group was determined qualitatively and semi-quantitatively by analysis of the DNA purified from daily blood samples, thereby providing a dynamic representation of each mixed infection. Effects on the course of parasitaemias are presented and discussed. PMID- 1461678 TI - Selection of specific genotypes of Giardia intestinalis by growth in vitro and in vivo. AB - This study examined whether allelic changes observed when clinical isolates of Giardia intestinalis made in suckling mice were adapted to in vitro growth occurred as a result of gene switching (alternate isoenzymes) or through selection of organisms with different genotypes from mixed infections. Samples were compared electrophoretically at 20 enzyme loci. Marked allelic differences were detected between the uncloned clinical isolates grown in mice and the axenic cultures established from them. Furthermore, the allelic profiles of the uncloned isolates changed during the course of in vivo or in vitro growth. In contrast, all clones produced from each isolate retained identical allelic profiles, regardless of whether they were grown in vivo or in vitro. These findings argue against gene switching as an explanation for the observed allozyme changes and support preferential selection of organisms with specific genotypes by growth conditions. The data indicate the presence of at least 2 and possibly up to 4 distinct genotypes within each clinical isolate. The genetic differences detected between clinical isolates in suckling mice were of similar magnitude to those that separate different axenic isolates of G. intestinalis into cryptic species. Conversely, the genetic differences between the isolates were limited when sampled after establishment in vitro. These findings have significant implications for research on Giardia and other medically important parasites and raise the possibility that culture may exert a similar selective bias on the genotypes isolated from infections with other parasitic protozoa. PMID- 1461679 TI - Proteinases of Trichomonas vaginalis: antibody response in patients with urogenital trichomoniasis. AB - Immunoprecipitation combined with electrophoresis in gelatin-polyacrylamide gels was successfully used for detection of antibodies against numerous proteinases of Trichomonas vaginalis in infected patients. The method proved to be highly specific as anti-proteinase antibodies were absent in women with negative cultivation of T. vaginalis and no history of trichomoniasis. Sera of 71% and vaginal washes of 86% patients with trichomoniasis were positive for these antibodies. In vaginal washes, but not in sera, antibodies were partly complexed with proteinases, possibly of trichomonad origin. It was also shown that serum antibodies as well as local anti-proteinase antibodies persisted for weeks after patients had been cured. PMID- 1461680 TI - Impairment of growth of Leishmania donovani by Trypanosoma brucei during co culture. AB - Cells of Leishmania donovani in co-culture with Trypanosoma brucei, were severely affected in their growth, resulting in swelling and subsequent lysis. Similar effects were also observed when Crithidia luciliae or Phytomonas sp. were co cultured with T. brucei. Direct contact between the cells under investigation and T. brucei was necessary because T. brucei did not hamper the growth of the other trypanosomatids, when separated by a filter with 0.2 microns pore size. Examination of this phenomenon at the ultrastructural level, in a co-culture of L. donovani and T. brucei, suggests that the plasma membrane permeability is increased in the former, as a result of a close cellular contact between the two cell types. PMID- 1461681 TI - Analysis of the complete sequence of a muscle calcium-binding protein of Schistosoma mansoni. AB - The complete sequence of the cDNA encoding a 20 kDa calcium-binding protein of Schistosoma mansoni (Sm20) has been determined. The predicted amino acid sequence contains 4 EF hand domains but examination of the predicted secondary structure of Sm20, together with the specific residues in each calcium-binding domain, suggests that only 1 EF hand (domain IV) is functional. Sm20 is most homologous to calmodulin, troponin C and the regulatory light-chain of myosin, particularly those of invertebrates. However, troponin C and the regulatory light-chain of myosin can be distinguished from Sm20 by size and by their differential levels of expression during the life-cycle. Sm20 also appears to be distinct from calmodulin but may be functionally equivalent to the soluble sarcoplasmic calcium binding proteins of molluscs and crustacea which may act as a reservoir for calcium in muscle. Sm20 is encoded by a small multi-gene family whose members are clustered within a 15 kb region of the genome. A 20 kDa antigen, cross-reactive with Sm20, is expressed in Schistosoma haematobium, Fasciola hepatica and Paragonomus mexicanus. PMID- 1461682 TI - Trichobilharzia ocellata infections in its snail host Lymnaea stagnalis: an in vitro study showing direct and indirect effects on the snail internal defence system, via the host central nervous system. AB - In this in vitro study we investigated whether previously described in vivo plasma-associated effects, that occurred in the period shortly after penetration of Trichobilharzia ocellata into the snail host Lymnaea stagnalis (1.5-72 h post exposure; p.e.) were direct and/or indirect effects of parasite-derived factor(s). It was investigated whether the effect is mediated by the central nervous system (CNS) of the host. Phagocytic activity of the haemocytes was taken as a parameter for the activity of internal defence of the host. A number of preliminary experiments were performed. When the supernatant of in vitro cultured parasites (33 h; corresponding with their developmental stage in vivo when plasma associated activation was found) was applied directly to monolayers of haemocytes, it appeared to enhance their phagocytic activity. No direct effect, however, was found with a supernatant of parasites cultured for a longer period of time (72 h; when, in vivo, a plasma-associated suppression was found). In this case, indirect suppression was detected: the parasites appeared to have released a factor that induced the CNS of the host to release material suppressing the activity of the internal defence system of the host. To date the nature of this factor is unknown. PMID- 1461683 TI - Theileria annulata-infected cells produce abundant proteases whose activity is reduced by long-term cell culture. AB - Lysates of Theileria annulata-infected bovine lymphoblastoid cells and their uninfected counterparts were tested for protease activity using gelatin substrate SDS-PAGE. The infected cells produced a number of extra activities at pH 8.0 in the presence of Ca2+. Calcium was found to enhance the activities but was not an absolute requirement. Studies using inhibitors, including E64, 3,4 dichloroisocoumarin, pepstatin and 1, 10-phenanthroline suggested that the activities were metalloproteases. We analysed two vaccine lines; the Ode line from India and the Ankara Pendik line from Turkey. In the Ode line the later passage had very much reduced levels of the enzyme activities. In the case of the Ankara Pendik line both stages analysed had very low protease activities, but a reduction from the early to late passage was also observed. The reduction in the level of protease activity was also observed as a gradual process during on-going culture of lines derived from the Hissar and Ode stocks. In the Ode line we demonstrated a parallel decrease in the production of microschizonts upon temperature shift in vitro. PMID- 1461685 TI - Host strain, H-2 genotype and immunocompetence do not affect the survival or development of Onchocerca lienalis infective larvae implanted within micropore chambers into mice or rats. AB - The survival, growth and development of Onchocerca lienalis 3rd-stage (L3) larvae implanted into mice within micropore chambers has been studied with a view to developing a vaccination model for studies of protective immunity in onchocerciasis. The influence of host genetics on worm recoveries and development (growth and moulting rate) was analysed in a panel of inbred mice (CBA, BALB/c, DBA/2, SJL, 129J, C57BL/10 (B10), C3H/He and NIH), together with mice of BALB and B10 backgrounds with different major histocompatibility complex (H-2) genes (BALB/c, BALB.K, BALB.B and B10, B10.D2/n, B10.BR, B10.S). Parasite recoveries and development were similar in all mouse genotypes tested. They were unaffected by procedures designed to block or modulate phagocytic cell function with carbon or carrageenan, or to suppress inflammation by treatment with hydrocortisone acetate. A comparison of chambers sealed with membranes designed to admit (5.0 microns pore size) or exclude (0.2 microns pore size) host cells demonstrated no effect on the percentage recovery of living larvae, although dead larvae were more frequently retrieved when cells were excluded. Recoveries and rates of development of larvae implanted into immunodeficient scid mice and athymic Hooded rats were similar to those recorded in immunocompetent controls. We conclude that host genetic factors and immunocompetence are not significant determinants of survival, growth or development of O. lienalis larvae implanted within micropore chambers into naive mice. Despite its limitations, the use of this system merits further investigation as an approach to the study of protective immunity against developing larvae in onchocerciasis. PMID- 1461684 TI - Antibodies against somatic antigens and excreted/secreted products of Brugia pahangi in rats with patent and non-patent infections. AB - The humoral responses of Sprague-Dawley rats infected with Brugia pahangi were examined for up to 6 months after infection by ELISA, immunoblotting, and IFAT. In 2 experiments, 50% and 62.5% of rats developed patent, microfilaraemic infections. Mean adult worm burdens at autopsy were approximately 2% of the inoculum, and only patent rats yielded living adult worms. IgG antibody levels against crude somatic extracts (CSE) of all parasite stages and against adult excreted/secreted (ES) products were significantly higher in patent than non patent rats. Both patent and non-patent rats produced anti-microfilarial surface antibody, as revealed by immunofluorescence. Immunostaining of Western blots by early infection sera showed no consistent difference in recognition of infective larval (L3) antigenic components by IgG or IgM antibody between eventually-patent and eventually-non-patent rats. By 26 weeks, however, patent rats recognized more components. The data suggest that antibodies against L3, adult, and microfilarial somatic antigens, ES antigens and microfilarial surface antigens do not correlate with the subsequent development of microfilaraemia in any individual rat. PMID- 1461686 TI - The effects of tumour necrosis factor on host-parasite relations in murine Mesocestoides corti (Cestoda) infection. AB - The regulatory role of tumour necrosis factor (TNF) was investigated in murine infection with tetrathyridia of Mesocestoides corti. Recombinant TNF alpha reduced macrophage larvicidal activity in vitro. M. corti primed mice for TNF release in response to bacterial lipopolysaccharide (LPS) in vivo. TNF activity was amplified 100-fold at 14 days post-infection (p.i.), with a further rise at day 28 p.i. Maximal inflammatory reaction was observed histologically in the liver at the height of TNF activity. Hepatic necrosis was located within inflammatory foci, but not within the vicinity of the parasite itself, suggesting that TNF may contribute to the pathogenesis of infection. Peritoneal cells from infected mice, when stimulated with tetrathyridia in vitro, showed a 4-fold increase in TNF alpha activity at day 14 p.i. However, when peritoneal cells were stimulated with LPS in vitro, a marked increase in TNF alpha secretion was observed at 2 months post-infection followed by a slow decline. It is suggested that impaired macrophage effector function, previously attributed to endogenous endotoxin, which gains access to peritoneal macrophages through an inability of the liver to detoxify endotoxin, may be mediated through TNF alpha. PMID- 1461687 TI - Epidemiology of nematode infections of Soay sheep (Ovis aries L.) on St Kilda. AB - The epidemiology of nematode infections of Soay sheep on the island of St Kilda over a period of 2 years (August 1988-August 1990) spanning a host population crash is described. Infective larvae (L3) levels on pasture were high (2422 +/- 365 L3/kg D.M. grass in midsummer 1988) when host population density was high, decreasing after the sheep population declined by 70% in early 1989 (601 +/- 14 L3/kg D.M. in midsummer 1989). The availability of infective larvae to sheep increased during the winter of 1988-1989, probably as a result of concentration of existing larvae on grass as vegetation was destroyed by bad weather and overgrazing. Increased availability of pre-parasitic stages was accompanied by a marked increased in faecal egg counts from sheep of all ages and both sexes. Prevalence and intensity of infection (faecal egg counts) were higher in males than females throughout the 2-year study (chi 2 = 208.3, P < 0.005 and F1, 2000 = 304, P < 0.001 respectively), except during the lambing periods, and decreased with age in both sexes. Changes in prevalence and intensity of strongyle infections were associated with changes in host population density. Prevalence and intensity of Dictyocaulus filaria larvae in faeces increased during the host population crash. Infection intensity decreased with age (F1, 203 = 44.02, P < 0.001) and was higher in males than females (F1, 203 = 13.45, P < 0.001). PMID- 1461688 TI - The role of nematode parasites in Soay sheep (Ovis aries L.) mortality during a population crash. AB - In early 1989, two-thirds of the Soay sheep population on St Kilda died over 12 weeks. Post-mortem examinations revealed emaciated carcasses and considerable nematode burdens, with protein-energy malnutrition as the probable cause of death. Haematological and blood biochemical changes in the sheep, as well as fecundity of gastrointestinal nematodes, suggested the hosts were immunosuppressed. In parallel, laboratory experiments in which Soay sheep on a high plane of nutrition were artificially infected with Ostertagia circumcincta, showed no clinical signs or mortality when supporting worm burdens similar to those recorded in dead sheep on St Kilda. Anthelmintic treatment of a group of animals increased daily survival rates in ewes and male lambs, although treated animals became re-infected as the 'crash' progressed. It is suggested that parasites contribute to mortality in malnourished hosts, exacerbating the effects of food shortage. PMID- 1461689 TI - Neuropeptide F (Moniezia expansa): localization and characterization using specific antisera. AB - Immunocytochemical techniques used in conjunction with confocal scanning laser microscopy (CSLM) and electron microscopy have been used to demonstrate, for the first time, the distribution of the parasitic platyhelminth neuropeptide, neuropeptide F (NPF) in the cestode, Moniezia expansa. Antisera were raised to intact NPF(1-39) and to the C-terminal decapeptide of NPF(30-39). These antisera were characterized and validated for use in both immunocytochemistry and radioimmunoassay (RIA). NPF immunoreactivity (IR) was detected using both antisera throughout all of the major components of the central and peripheral nervous systems of the worm. The pattern of NPF-IR was found to mirror the IR obtained using a C-terminally directed pancreatic polypeptide (PP) antiserum and FMRFamide antisera; blocking studies using these antisera revealed that FMRFamide and PP antisera cross-react with NPF(M. expansa). RIA of acid-alcohol extracts of the worm measured 114 ng/g using the C-terminal NPF antiserum and 56 ng/g using the whole-molecule-directed antiserum. While the C-terminally-directed NPF antiserum cross-reacts with NPF-related peptides from other invertebrates, the whole-molecule-directed NPF antiserum is specific for NPF(M. expansa). The C terminal NPF antiserum has potential for use in the identification and purification of NPF analogues from other platyhelminth parasites. PMID- 1461690 TI - Population-based study of measles and measles immunization in human immunodeficiency virus-infected children. AB - This study reports the course of measles and results of measles immunization in a cohort of human immunodeficiency virus-infected children. Six cases of measles were identified. All had typical clinical manifestations, 5 of 6 developed pneumonia and 3 of 6 died. A measles intervention program consisting of serologic screening and active immunization (measles-mumps-rubella (MMR)) was instituted in 1990. Among 127 children with data available for analysis (mean age, 6.7 years), only 35% had documentation of prior immunization with MMR. Among 80 children who had preimmunization measles serology reported, 56% were measles antibody-negative and 40% were antibody-positive; following intervention 36% remained measles antibody-negative. Six children lost measles antibody over time. MMR nonresponders had lower CD4 lymphocyte counts (303 +/- 394) compared with responders (865 +/- 677; P = 0.0058). Measles is a potentially fatal illness in human immunodeficiency virus-infected children. Prevention strategies are limited by low rates of age-appropriate MMR immunization, poor antibody responses to MMR in older human immunodeficiency virus-infected children and seroreversion. PMID- 1461691 TI - Infectious risks of Broviac catheters in children with neoplastic diseases: a matched pairs analysis. AB - In the present study the complication rate of Broviac catheters in the therapy of children with cancer was determined. Of special interest was the question of to what extent the incidence of bacteremias is increased by the implant. For this reason the method of matched pairs analysis was chosen comparing 55 patients with 61 catheters to 1 child each who received the therapy via peripheral veins. Apart from having the same disease, the same therapy protocol and the same age group the partners had a similar number of leukocytopenic days (leukocyte counts, < 1000/microliters) in the study period. The observation time was 9671 days in the catheter group and 9666 days in the control group. During this time 167 fever episodes (17.7 episodes/1000 days) were recorded in the patients with implant but only 133 episodes (14.0/1000 days) in the control patients. Study and control groups had similar frequencies of fever of unknown origin with leukocyte counts > or = 1000/microliters and fever with a known focus. However, 29 bacteremias (2.9 episodes/1000 days) represented a 4 times higher complication rate with the use of Broviac catheters than in the control group (7 bacteremias, 0.7 episode/1000 days). Episodes of fever of unknown origin with leukocytopenia were 1.5 times more common in the catheter group than in the control group. Although it is not possible to prove that the catheter played a role as focus of bacterial infection, an increased risk of infection must be supposed. The Broviac catheter meets with broad approval by the patients, parents and medical staff.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461692 TI - Prophylaxis of ophthalmia neonatorum: comparison of silver nitrate, tetracycline, erythromycin and no prophylaxis. AB - From November, 1989, to October, 1991, 4544 neonates were born at our hospital. Neonatal ocular prophylaxis immediately after birth was used with 1% tetracycline ophthalmic ointment in 1156 neonates, 0.5% erythromycin ophthalmic ointment in 1163 neonates and 1% silver nitrate drops in 1082 neonates. No prophylaxis for neonatal conjunctivitis was given to 1143 neonates. A total of 302 infants (6.7%) developed conjunctivitis during the first 4 weeks of life. Between December, 1991, and January, 1992, 425 neonates were born at our hospital and all were given 0.5% erythromycin ophthalmic ointment twice in the first 24 hours after birth for ocular prophylaxis. Thirty-one (7.3%) infants developed conjunctivitis during the neonatal period. The incidence rates of neonatal chlamydial conjuctivitis in the tetracycline, erythromycin, silver nitrate, no prophylaxis and erythromycin twice groups were 1.3, 1.5, 1.7, 1.6 and 1.4%, respectively. We conclude that neonatal ocular prophylaxis with erythromycin (one or two doses) or tetracycline or silver nitrate does not significantly reduce the incidence of neonatal chlamydial conjunctivitis compared with that in those given no prophylaxis. PMID- 1461693 TI - Coagulase-negative staphylococcal bacteremia in severely malnourished Jamaican children. AB - Immunosuppression increases the susceptibility to infection and changes the inflammatory response in children with severe protein-energy malnutrition. In this 5-year prospective study bacteremia was documented in 16% of 336 severely malnourished children, 2 to 34 months of age, who were hospitalized consecutively in the Tropical Metabolism Research Unit, Kingston, Jamaica. The 53 children had 60 episodes of nosocomial and community-acquired bacteremia with 69 blood isolates. Community-acquired bacteremia accounted for 72% (43 of 60) of bacteremic episodes. Thirty-five percent (24 of 69) of the strains were coagulase negative staphylococci, 19% (13 of 69) were Staphylococcus aureus and 11% (8 of 69) were Streptococcus Group D. Seventeen episodes of coagulase-negative staphylococcal bacteremia were acquired in the community and 7 were nosocomial. These patients were more likely to have pneumonic consolidation than children with all other bacteremias combined (P < 0.02, Fisher's exact test). The bacteremia-related case fatality rate was 8% (5 of 60). Polymicrobial and Gram negative septicemia were independent positive predictive factors for mortality when compared with single-agent and Gram-positive sepsis (P < 0.02). This 71% (49 of 69) prevalence of Gram-positive organisms suggests a change in the epidemiology from the predominant Gram-negative etiologies (76%) described in previous reports. PMID- 1461694 TI - Intensive short course chemotherapy for treatment of Greek children with tuberculosis. AB - This prospective study with an 18-month posttreatment follow-up evaluated the efficacy of intensive short course chemotherapy in Greek children with pulmonary or extrapulmonary tuberculosis. Between November, 1988, and March 1991 a 2-month regimen of rifampin, 10 to 12 mg/kg/day, isoniazid, 10 to 12 mg/kg/day, and pyrazinamide, 30 to 35 mg/kg/day, followed by rifampin and isoniazid for the remaining 4 months, was administered orally to 36 children with tuberculosis. Twenty-three boys and 13 girls ages 8 months to 12 years (mean, 5 1/2 years) were enrolled in the study. The diagnostic criteria for establishing tuberculosis were tuberculin skin test reactivity, radiographic findings compatible with tuberculosis, epidemiological data and clinical and laboratory findings. Four children had extrapulmonary and 32 had pulmonary tuberculosis; 9 of the latter were asymptomatic. Among the pulmonary cases there were 2 children with pleural effusion. Clinical response to therapy was apparent within 7 to 14 days; the pleural effusions resolved in 2 to 6 weeks and the pulmonary infiltrates cleared in 2 to 6 months. Hilar adenopathy regressed within 18 months or longer. No serious problems with drug tolerance or toxicity were noted during the treatment period. Temporary hyperuricemia and transient elevation in serum transaminases were observed in 11 patients but no drug modification was required. There were no posttreatment relapses. These findings suggest that intensive short course chemotherapy for the treatment of Greek children with pulmonary or extrapulmonary tuberculosis appears to be effective, safe, of good patient compliance and comparable to the longer treatment regimens. PMID- 1461695 TI - Role of the new quinolones in pediatric practice. PMID- 1461696 TI - Morphologic studies for skeletal toxicity after prolonged ciprofloxacin therapy in two juvenile cystic fibrosis patients. PMID- 1461697 TI - Varicella-zoster contracted in the second trimester of pregnancy. PMID- 1461698 TI - Type b and non-type b Haemophilus influenzae endocarditis. PMID- 1461699 TI - Serum C-reactive protein vs. tumor necrosis factor alpha and interleukin 1 beta of the cerebrospinal fluid in diagnosis of bacterial meningitis with low cerebrospinal fluid cell count. PMID- 1461700 TI - Disseminated cat-scratch disease simulating neuroblastoma. PMID- 1461701 TI - Group A Streptococcus mural endocarditis. PMID- 1461702 TI - Congenital malformations in an infant born to a woman treated with fluconazole. PMID- 1461703 TI - Angiostrongylus cantonensis infection in infants and young children. PMID- 1461704 TI - Unusual presentation of group B Streptococcus osteomyelitis. PMID- 1461705 TI - Streptococcal pyomyositis in two adolescent patients. PMID- 1461706 TI - Mumps with presternal edema-Gellis sign. PMID- 1461707 TI - Plasma arginine vasopressin and syndrome of inappropriate antidiuretic hormone secretion in tuberculous meningitis. PMID- 1461708 TI - Immunodeficiency in asplenia. PMID- 1461709 TI - Trimethoprim-sulfamethoxazole prophylaxis of Pneumocystis carinii pneumonia in infants. PMID- 1461711 TI - Drug Utilization Research and Pharmacoepidemiology Meeting. Utrecht, The Netherlands, 27 November 1992. Abstracts. PMID- 1461710 TI - Diarrhea among African children born to human immunodeficiency virus 1-infected mothers: clinical, microbiologic and epidemiologic features. AB - Diarrhea and weight loss are common features of pediatric and adult human immunodeficiency type 1 (HIV-1) infection, particularly in developing countries. We studied prospectively episodes of diarrhea in 559 children, ages 10 to 15 months, participating in a longitudinal study of perinatal HIV-1 infection in Kinshasa, Zaire. Children with HIV-1 infection had more frequent episodes of diarrhea and were more likely to present with fever or moderate or severe dehydration and to have persistent or fatal diarrhea. Of 9 HIV-1-positive infants with diarrhea, 3 had enteroadherence factor-positive Escherichia coli, compared with 5 of 74 HIV-1-negative children with diarrhea (P = 0.04); no other pathogen was associated with HIV-1 infection. In a logistic regression model diarrhea was significantly associated with HIV-1 infection in the child, moderate or severe malnutrition and symptoms of acquired immunodeficiency syndrome in the mother. Diarrhea among children with perinatal HIV infection in Zaire is more severe than among uninfected children and is associated with malnutrition and advanced disease in the mother. PMID- 1461712 TI - Pharmacological Meeting. Lunteren, The Netherlands, 14-15 December 1992. Abstracts. PMID- 1461713 TI - Aromatic aldehydes and aromatic ketones open ATP-sensitive K+ channels in guinea pig ventricular myocytes. AB - Patch-clamp techniques were used to study the effects of three carbonyl compounds, 3,4-dihydroxybenzaldehyde, 2,3-dihydroxybenzaldehyde, and 2,4 dihydroxyacetophenone, on the adenosine-5'-triphosphate(ATP)-sensitive K+ channel current (IK.ATP) in guinea-pig ventricular myocytes. 3,4-Dihydroxybenzaldehyde (0.5-1 mM) shortened the action potential duration, and this effect was inhibited by application of a specific blocker of IK.ATP, glibenclamide. The shortening of the action potential duration was shown to be caused by a time-independent outward current. In the cell-attached patch configuration, all three compounds activated a kind of single-channel current, which showed an inward rectification at positive potentials and which had a linear current/voltage relation at negative potentials, having a conductance of 90 pS. The current reversed at about 0 mV in symmetrical K+ concentrations on both sides of the membrane. In excised patches this current was blocked by internal application of ATP. Thus we identified this channel as IK.ATP. The activation effects of two aromatic aldehydes were stronger than that of the aromatic ketone. The effect of these compounds on IK.ATP was not reduced by addition of cysteine (10 mM). In inside out patches, 3,4-dihydroxybenzaldehyde increased the activity of IK.ATP, which had been blocked by 0.5 mM MgATP in the presence of 0.5 mM ADP, but the activation effect was variable and much weaker than that in the cell-attached configuration, and was completely eliminated in the absence of ADP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461714 TI - Effects of inhibitors and ion substitutions on oscillations of cell membrane potential in cells expressing the RAS oncogene. AB - Previous studies revealed that in NIH fibroblasts expressing the ras oncogene but not in other NIH fibroblasts, bradykinin leads to sustained, calcium dependent oscillations of cell membrane potential by repetitive activation of calcium sensitive K+ channels. The present study has been performed to test for ion and inhibitor sensitivity of these oscillations. Both, Lys-bradykinin (kallidin) and bradykinin, but not any shorter peptide tested, maintained the oscillations. The oscillations are abolished in the presence of the K+ channel blocker barium (10 mmol/l). The amplitude but not the frequency of the oscillations is dependent on the extracellular potassium concentration. The oscillations are not dependent on the presence of extracellular sodium, bicarbonate or chloride. The oscillations are abolished in the absence of extracellular calcium and their frequency is significantly decreased at reduced extracellular calcium (to 0.2 mmol/l). The oscillations are not inhibited by acute administration of ouabain (0.1 mmol/l), by dimethylamiloride (100 mumol/l), furosemide (1 mmol/l) and hydrochlorothiazide (100 mumol/l), by cobalt (100 mumol/l), zinc (100 mumol/l), gadolinium (100 mumol/l), verapamil (10 mumol/l) and diltiazem (10 mumol/l), but are abolished in the presence of 100 mumol/l lanthanum, 1 mmol/l cadmium, 10 mumol/l nifedipine, 25 mumol/l SK & F 96365 and 200 mumol/l TMB-8. Stimulation of calcium entry by 10 nmol/l ionomycin is frequently followed by oscillations of cell membrane potential even in the absence of bradykinin. In conclusion, in cells expressing the ras oncogene bradykinin leads to sustained activation of calcium channels at the cell membrane, which cause oscillations of the cell membrane potential by triggering intracellular calcium release. PMID- 1461715 TI - Substrate specificity of the luminal Na(+)-dependent sulphate transport system in the proximal renal tubule as compared to the contraluminal sulphate exchange system. AB - The efflux of [35S]sulphate from the lumen of the proximal renal tubule into tubular cells of rats was measured by the stop-flow tubular-lumen microperfusion technique. The transport parameters obtained and the apparent Ki values of competing substrates were compared with those of the contraluminal influx of [35S]-sulphate from the interstitium into tubular cells. For the luminal sulphate efflux a Km(l, SO4(2-)) of 0.8 mmol/l and a Jmax(l, SO4(2-)) of 0.2 pmol s-1 cm-1 were found. The corresponding contraluminal values were Km(cl,SO4(2-)) 1.4 mmol/l and Jmax(cl,SO4(2-)) 1.2 pmol s-1 cm-1. Omission of Na+ from the perfusates reduced the luminal efflux of sulphate by 83%, while the contraluminal influx of sulphate was not changed. Increase in HCO3- concentration inhibited both luminal efflux and contraluminal influx of sulphate, while a change of pH from 6.0 to 8.0 was without effect. Comparing the apparent Ki(SO4(2-)) values for luminal and contraluminal sulphate transport, a relationship close to 1:1 was seen for some inorganic substrates with tetrahedral molecular structure (thiosulphate, sulphate, molybdate and selenate). The same holds for phosphate, while for oxalate the contraluminal Ki(SO4(2-)) value was lower than the luminal one (1.2 and 4.5 mmol/l). Some of the dicarboxylates and disulphonates tested show the same affinity to the luminal Na(+)-dependent sulphate transporter and the contraluminal sulphate exchange system, whereas most of the benzene carboxylate and benzenesulphonate derivatives tested exhibit higher luminal than contraluminal Ki values. The inhibitory potency increased with rising numbers of substituents on the benzene ring. This effect was more pronounced for the contraluminal sulphate transporter. In general, only disulphonates and analogues as well as similarly structured compounds (5-sulphosalicylate, 2-hydroxy-5 nitrobenzenesulphonate, eosine-5-isothiocyanate) have a good inhibitory potency toward the luminal sulphate transporter [apparent Ki 0.9-3.1 mmol/l]. All the tested sulphamoyl and phenoxy diuretics, and fluorescein and phenolphthalein dyes showed no or a smaller inhibitory potency to the luminal sulphate transport system than to the contraluminal. The most effective inhibitors of both sulphate transport systems are 8-anilino-1-naphthalenesulphonate, orange G, and H2-DIDS. The data indicate that the Na(+)-dependent luminal and the Na(+)-independent contraluminal sulphate transport systems accommodate a similar spectrum of anionic substrates, whereby the inhibitory potency against the luminal Na(+) dependent sulphate transport system is identical or smaller than against the contraluminal transporter. PMID- 1461716 TI - Lack of effect of intraluminal pressure on renin release from isolated afferent arterioles. AB - To evaluate the role of the proposed baroreceptor mechanism in the afferent arteriole in regulating renin release, we modified the isolated perfused tubule technique to perfuse afferent arterioles. Arterioles with attached glomeruli were isolated from rabbit kidneys and perfused using standard methods. To stop the arteriolar flow and allow perfusion pressure, as set by a mercury manometer, to be built up in the lumen of the vessel, the glomerulus was sucked into a constriction pipette. The preparation was continuously superfused with Krebs Ringer solution in the first series of experiment, and a cell culture medium in the second series of experiment. The superfusate droplets were collected under mineral oil with 10-min collection intervals. The renin content of the samples was assayed by radioimmunoassay of the angiotensin I generated. In the two series of experiments we tested the effects of sequential changes in intraluminal pressure on renin release. In the first series of experiments (n = 6) the renin release was 56.3 nGU arteriole-1 min-1 in the first 10 min of sampling. The renin release was then constant for 80 min with an average of 21.6 nGU arteriole-1 min 1. In the last 30 min the renin release was 96.5 nGU arteriole-1 min-1. In the second series of experiments (n = 8) the renin release was 26.5 nGU arteriole-1 min-1 throughout the course of the experiment. These results indicate that under these conditions there is no relation between renin release and intraluminal pressure in afferent arterioles. PMID- 1461717 TI - Relation between slow-wave frequency and spiking activity during the migrating myoelectric complex in dogs. AB - The quantitative relation between slow-wave periods and spiking activity was evaluated in vivo in canine small intestine during the fasted state. Experiments were performed in three conscious dogs with three bipolar electrodes, implanted respectively 10, 25 and 40 cm beyond the ligament of Treitz. Digitized electrical recordings were automatically processed for the individual slow-wave periods and spike-burst intensities using a set of computer programs developed in our laboratory. A linear correlation existed between the degree of spiking activity and the average length of the preceding slow-wave period. The slopes of the regression lines were less steep for more distal electrodes. A second series of experiments showed that an increase in the slow-wave period precedes the onset of phase 3 of the migrating myoelectric complex and that a fall in slow-wave period precedes the end of phase 3. These data show that a low slow-wave frequency is accompanied by a facilitation of spiking activity, whereas shortening of the slow wave period is accompanied by a decrease in spike burst intensity. This relation between slow-wave period and spiking activity shows an aboral trend that may be related to intrinsic slow-wave frequency. PMID- 1461718 TI - Epidermal growth factor stimulates Ca2+ uptake of human erythrocytes. AB - To examine the functional significance of epidermal growth factor (EGF) binding sites present on the human erythrocyte membrane [Engelmann et al. (1992) Am J Hematol 39:239-241], the effect of EGF on 45Ca2+ uptake and on 22Na+ efflux from these cells has been studied. In all cases media contained 1.25 mM Ca2+, whereas Na+ and K+ were varied. In 140 mM Na+/5 mM K+ medium EGF (250 ng/ml) stimulated 45Ca2+ uptake by 50%-90% in quin-2-loaded cells, and by up to threefold in untreated cells. Increasing extracellular K+ up to 75 mM at the expense of extracellular Na2+ stimulated the EGF-induced 45Ca2+ uptake by about twofold compared to 145 mM Na+ medium both in quin-2-loaded and in untreated cells. In 145 mM K+ medium, however, no EGF-induced 45Ca2+ uptake was detectable in quin-2 loaded cells, while in untreated cells Ca2+ entry was stimulated twofold by EGF. After increasing intracellular Na+ from 6 mmol/l cells to 18 mmol/l cells in untreated cells suspended in 145 mM K+ medium, 45Ca2+ uptake induced by EGF gradually increased. In contrast, in 140 mM Na+/5 mM K+ as well as in 70 mM Na+/75 mM K+ medium, 45Ca2+ uptake accelerated by EGF was largely unaffected by a modified red cell Na+ content. When 22Na-loaded untreated red cells were suspended in 145 mM K+ medium EGF stimulated red cell 22Na+ efflux by more than threefold. In 140 mM Na+/5 mM K+ as well as in 70 mM Na+/75 mM K+ medium, no 22Na+ efflux induced by the growth factor was evident.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461719 TI - Involvement of a pertussis toxin-sensitive G-protein in excitation-contraction coupling of intact and cut-end voltage-clamped skeletal muscle fibres. AB - In voltage-clamped frog muscle fibres 10 ng/ml PTX induced a decrease (approximately 35%) of tension when applied externally. Internal application in cut-end fibres significantly depressed tension after 20 min. This effect increased with time to reach 65% after 60 min. PTX shifted the voltage-dependent inactivation curve of tension by 30 mV towards hyperpolarizations and this was counteracted by raising external calcium concentration. The toxin induced a parallel decrease in tension and voltage-sensitive charge movement (49 +/- 9% and 52 +/- 6% respectively; n = 6). This was not counteracted by prior impregnation with forskolin. Internally applied GTP gamma S (500 microM) induced a simultaneous increase in tension (57 +/- 5%) and charge amount displaced (40 +/- 7%). By contrast, GDP beta S decreased tension and charge movement by 35 +/- 5% and 36 +/- 6% respectively. PMID- 1461720 TI - Effects of neuronal bungarotoxin and nitric oxide inhibitors on the post iontophoretic burst of miniature end-plate currents at the frog neuromuscular junction. PMID- 1461721 TI - Cofractionation of the TATA-binding protein with the RNA polymerase III transcription factor TFIIIB. AB - We have investigated the requirement for TBP (TATA-binding protein) in transcription mediated by RNA polymerase III (pol III) in fractionated HeLa cell extracts. Two activities, TFIIIB and TFIIIC, found in phosphocellulose fractions PC B and PC C respectively, have been defined as necessary and sufficient, with pol III, for in vitro transcription of tRNA genes. Depletion of TBP from PC B, using antibodies raised against human TBP, is shown to inhibit the pol III transcriptional activity of the fraction. Furthermore, TBP is present in fractions with human TFIIIB activity, and a proportion of TBP cofractionates with TFIIIB over four chromatographic purification steps. TFIIIB fractions are capable of supplying TBP in the form necessary for pol III transcription, and cannot be substituted by fractions containing other TBP complexes or TBP alone. The use of a 5S RNA gene and two tRNA templates supports the general relevance of our findings for pol III gene transcription. Purified TFIIIB activity can also support pol II-mediated transcription, and is found in a complex of approximately 230kD, suggesting that TFIIIB may be the same as the previously characterized B TFIID complex (1,2). We suggest that transcription by the three RNA polymerases is mediated by distinct TBP-TAF complexes: SL1 and D-TFIID for pol I and pol II respectively, and TFIIIB for pol III. PMID- 1461722 TI - Characterization of the self-splicing products of a mobile intron from the nuclear rDNA of Physarum polycephalum. AB - We have characterized the splicing products formed in vitro from RNA derived from the mobile group I intron in the nuclear rDNA of Physarum polycephalum, Pp LSU 3. This intron is a close relative of the well known Tetrahymena intron Tt LSU 1, being inserted at exactly the same position in the rDNA and sharing about 90% sequence identity with Tt LSU 1 in the conserved elements characteristic of the catalytic core of all group I introns. However, Pp LSU 3 differs from Tt LSU 1 in that it encodes a site-specific endonuclease, which mediates the homing of the intron to unoccupied target sites. The endonuclease, I-Ppo, would appear to be a unique example of a protein encoded by an RNA polymerase I transcript. To gain clues to the splicing products formed in vivo, and to the nature of the messenger RNA for I-Ppo, we subjected Pp LSU 3 RNA to standard self-splicing conditions in vitro, and then analyzed the products by size, by northern blotting, and by primer extension. The results show two novel features. First, in addition to the expected 5' splice site, there is an alternative 5' splice site in the upstream exon, just preceding the first codon of the I-Ppo open reading frame. Second, at the position corresponding to the major circularization site in Tt LSU 1 there is an internal processing site, leading to the efficient separation of two halves of the excised intron, the 5' half encoding I-Ppo and 3' half containing the ribozyme. Surprisingly, this cleavage appears not to be due to circularization followed by hydrolytic opening of the circle, but rather to G addition. The formation of these products in vitro suggests how the messenger RNA for the I-Ppo endonuclease may be generated in vivo. PMID- 1461723 TI - Elongation factor-1 messenger-RNA levels in cultured cells are high compared to tissue and are not drastically affected further by oncogenic transformation. AB - Copy-DNA clones covering the complete coding sequence of human Elongation Factor 1 gamma mRNA have been isolated and characterized. The expression of Elongation Factor-1 in a variety of cell lines and a number of tissues shows a large increase in Elongation Factor-1 mRNA going from tissue to cultured cells (20 fold). Messenger-RNA levels for Elongation Factor-1 alpha, -1 beta and -1 gamma increase in parallel suggesting coordinate regulation of the expression of these genes. Oncogenic transformation in vitro does not strongly affect Elongation Factor-1 mRNA levels. PMID- 1461725 TI - The FLP protein contacts both major and minor grooves of its recognition target sequence. AB - The FLP protein of the 2 microns plasmid of Saccharomyces cerevisiae promotes conservative site-specific recombination between DNA sequences that contain the FLP recognition target (FRT). FLP binds to each of the three 13 base pair symmetry elements in the FRT site in a site-specific manner. We have probed both major and minor groove contacts of FLP using dimethyl sulphate, monoacetyl-4 hydroxyaminoquinoline 1-oxide and potassium permanganate and find that the protein displays extensive interactions with residues of both the major and minor grooves of 10 base pairs of each symmetry element. We find no evidence that the FRT site assumes a single-stranded conformation upon FLP binding. PMID- 1461726 TI - Mutagenesis analysis of the self-cleavage domain of hepatitis delta virus antigenomic RNA. AB - To determine the sequence requirements and structural features of the self cleavage domain of hepatitis delta virus (HDV) antigenomic RNA, we constructed a series of mutants and measured the rate constant of the cleavage reaction for each. The self-cleavage activity of HDV RNA of antigenomic sense was found to reside in a region of less than 90 nucleotides in length. The catalytic domain contained a long complementary sequence which could be deleted to half of its original size. Moreover, this region could be replaced by other sequences as long as they could fold into a stem-and-loop structure. The catalytic domain also required a 6-basepair helix adjacent to the cleaving point for activity. The structural features of these two base-pairing regions are quite similar to those of the HDV genomic self-cleavage domain. The cleavage site as well as the the hinge region (the sequence between the two stems) requires specific sequences for activity. PMID- 1461724 TI - Pseudouridine in the anticodon G psi A of plant cytoplasmic tRNA(Tyr) is required for UAG and UAA suppression in the TMV-specific context. AB - We have previously isolated and sequenced Nicotiana cytoplasmic tRNA(Tyr) with G psi A anticodon which promotes readthrough over the leaky UAG termination codon at the end of the 126 K cistron of tobacco mosaic virus RNA and we have demonstrated that tRNA(Tyr) with Q psi A anticodon is no UAG suppressor. Here we show that the nucleotide in the middle of the anticodon (i.e., psi 35) also contributes to the suppressor efficiency displayed by cytoplasmic tRNA(Tyr). A tRNA(Tyr) with GUA anticodon was synthesized in vitro using T7 RNA polymerase transcription. This tRNA(Tyr) was unable to suppress the UAG codon, indicating that nucleotide modifications in the anticodon of tRNA(Tyr) have either stimulating (i.e., psi 35) or inhibitory (i.e., Q34) effects on suppressor activity. Furthermore, we have shown that the UAA but not the UGA stop codon is also efficiently recognized by tobacco tRNA(G psi ATyr), if placed in the TMV context. Hence this is the first naturally occurring tRNA for which UAA suppressor activity has been demonstrated. In order to study the influence of neighbouring nucleotides on the readthrough capacity of tRNA(Tyr), we have established a system, in which part of the sequence around the leaky UAG codon of TMV RNA was inserted into a zein pseudogene which naturally harbours an UAG codon in the middle of the gene. The construct was cloned into the vector pSP65 and in vitro transcripts, generated by SP6 RNA polymerase, were translated in a wheat germ extract depleted of endogenous mRNAs and tRNAs. A number of mutations in the codons flanking the UAG were introduced by site-directed mutagenesis. It was found that changes at specific positions of the two downstream codons completely abolished the readthrough over the UAG by Nicotiana tRNA(Tyr), indicating that this tRNA needs a very specific codon context for its suppressor activity. PMID- 1461727 TI - Detection and characterization of a ring chromosome in the fission yeast Schizosaccharomyces pombe. AB - NotI and SfiI genomic restriction maps were used to detect and characterize a ring chromosome II in a Schizosaccharomyces pombe strain with a meiotic defect on chromosome II. The ring chromosome was formed by an intrachromosomal fusion near, or at, the very ends of chromosome II. PMID- 1461728 TI - Retinoblastoma-repression of E2F-dependent transcription depends on the ability of the retinoblastoma protein to interact with E2F and is abrogated by the adenovirus E1A oncoprotein. AB - The product of the retinoblastoma tumor suppressor gene interacts with the transcription factor E2F. Two distinct types of interactions can be detected between the retinoblastoma gene product (Rb) and E2F. The first type involves an Rb-binding protein, RBP60. The Rb/E2F complex formed in the presence of RBP60 is able to bind DNA and migrates with a distinct mobility in gel retardation assays. The second type of Rb/E2F complex is seen in the absence of RBP60. This second type of Rb/E2F complex does not form a band-shift complex in gel retardation assays and its formation results in an apparent inhibition or loss of the DNA binding activity of E2F. Using a series of Rb-mutants we show that these two types of Rb/E2F complexes depend on common domains of the Rb protein. The T/E1A binding region as well as the carboxyl-terminus of the Rb protein are critical for these two types of Rb/E2F interactions. We also show that the retinoblastoma protein represses the E2F-dependent transcription, and this Rb-repression of the E2F-dependent transcription depends on the ability of Rb to interact with E2F. Moreover, the adenovirus E1A gene product, which binds Rb, counteracts the Rb repression and restores E2F-dependent transcription. PMID- 1461729 TI - Regulatory gene INO4 of yeast phospholipid biosynthesis is positively autoregulated and functions as a transactivator of fatty acid synthase genes FAS1 and FAS2 from Saccharomyces cerevisiae. AB - The sequence motif 5' TYTTCACATGY 3' functions as an upstream activation site common to both yeast fatty acid synthase genes, FAS1 and FAS2. In addition, this UASFAS element is shared by all so far characterized genes of yeast phospholipid biosynthesis. We have investigated the influence of a functional INO4 gene previously described as a regulator of inositol biosynthesis on the expression of FAS1 and FAS2. In a delta ino4 null allele strain, both genes are expressed at only 50% of wild type level. Using individual UASFAS sequence motifs inserted into a heterologous test system, a drastic decrease of reporter gene expression to 2-10% of the wild type reference was observed in the delta ino4 mutant. In gel retardation assays, the protein-DNA complex involving the previously described FAS binding factor 1, Fbf1, was absent when using a protein extract from the delta ino4 mutant. On the other hand, this signal was enhanced with an extract from cells grown under conditions of inositol/choline derepression. Subsequent experiments demonstrated that INO4 expression is itself affected by phospholipid precursors, mediated by an UASFAS element in the INO4 upstream region. Thus, in addition of being an activator of phospholipid biosynthetic genes, INO4 is also subject to a positive autoregulatory loop in its own biosynthesis. PMID- 1461730 TI - Analysis of the autonomous replication behavior in human cells of the dihydrofolate reductase putative chromosomal origin of replication. AB - Chinese hamster genomic DNA sequences from the region downstream of the dihydrofolate reductase (DHFR) gene reported to contain a chromosomal origin of bidirectional DNA replication (OBR-1) were tested for their ability to support autonomous DNA replication in human cells. A 13.3 kilobase fragment containing OBR-1 and surrounding sequences supported replication in short-term and long-term replication assays, while a 4.5 kb fragment containing OBR-1 did not support substantial replication in either assay. These results are consistent with our previous observations that large fragments of human DNA support replication, while smaller fragments are less efficient. The replication activities of plasmids containing OBR-1 were no greater than those of randomly chosen human fragments of similar size. Furthermore, two-dimensional gel analysis of plasmids containing OBR-1 indicated that initiation does not preferentially occur within the OBR-1 region. These results suggest that in the context of autonomous replication, the DHFR sequences tested do not contain genetic information specifying site-specific replication initiation. Possible implications of these results for chromosomal replication are discussed. PMID- 1461731 TI - TGA cysteine codons and intron sequences in conserved and nonconserved positions are found in macronuclear RNA polymerase genes of Euplotes octocarinatus. AB - The gene sequences of the second largest subunits of RNA polymerases I and II of Euplotes octocarinatus, RPA2 and RPB2, were determined and compared to the respective known sequences of Saccharomyces cerevisiae. The similarity of the derived polypeptide sequences permitted their assignment to the respective polymerases and allowed the comparison of the zinc binding regions. In frame TGA codons were detected, which are likely to encode conserved cysteinyl residues in the putative zinc-finger region of the RPA2 gene. They were also found in other positions in both the RPA2 and RPB2 genes. The RPB2 gene contains a 30 bp intron close to the 5'-end of its coding region. The 5'-ends of the coding regions of all three genes encoding the largest subunits of the three different polymerases were also analyzed. The zinc finger structures again show the use of TGA codons for conserved cysteinyl residues in two of the genes. An N-terminal intron is located in the RPB1 gene at a conserved position as compared to the respective genes of several other eucarya. PMID- 1461732 TI - Transcriptionally driven cruciform formation in vivo. AB - We studied the formation of d(A-T)n cruciforms in E.coli cells by probing intracellular plasmid DNA with chloroacetaldehyde followed by fine analysis of modified DNA bases. d(A-T)16 sequences were inserted into specifically designed plasmids either upstream of a single trc promoter, or between two divergent trc promoters. We found that in both cases, induction of transcription by IPTG leads to the transition of the d(A-T)16 stretch into a cruciform state. In the case of two divergent promoters, we observed cruciform formation even without IPTG. Enhanced cruciform formation correlates with the elevation in promoter activity as defined by the opening of the promoter at the -10 to +2 positions. We conclude that transcriptionally driven negative supercoiling provokes cruciform formation in vivo. PMID- 1461733 TI - Three distinct RNA sequence elements are required for efficient apolipoprotein B (apoB) RNA editing in vitro. AB - Apolipoprotein B (apoB) mRNA is edited in rat liver and intestine to convert a CAA glutamine codon to a UAA translational stop codon by the direct conversion of cytidine to uridine at nucleotide 6666. We have proposed the 'mooring sequence' model for apoB RNA editing, in which editing complexes (editosomes) assemble on specific apoB mRNA flanking sequences to direct this site-specific editing event. One sequence element (approx. nts 6671-81, the presumed 'mooring sequence') has been previously identified as necessary for editing. We have identified two additional sequence elements which are necessary for efficient editing: (1) a 5' 'Regulator' region which modulates editing efficiency and (2) a 'Spacer' region between the editing site and the 3' mooring sequence, whose distance is critical for efficient editing. Utilizing this data, we have induced editing at a cryptic site and have defined a 22 nucleotide 'cassette' of specific apoB sequence which is sufficient to support wild-type levels of editing in vitro in a background of distal apoB RNA sequence. PMID- 1461735 TI - PCR amplification of tandemly repeated DNA: analysis of intra- and interchromosomal sequence variation and homologous unequal crossing-over in human alpha satellite DNA. AB - Tandemly repeated DNA can comprise several percent of total genomic DNA in complex organisms and, in some instances, may play a role in chromosome structure or function. Alpha satellite DNA is the major family of tandemly repeated DNA found at the centromeres of all human and primate chromosomes. Each centromere is characterized by a large contiguous array of up to several thousand kb which can contain several thousand highly homogeneous repeat units. By using a novel application of the polymerase chain reaction (repPCR), we are able to amplify a representative sampling of multiple repetitive units simultaneously, allowing rapid analysis of chromosomal subsets. Direct sequence analysis of repPCR amplified alpha satellite from chromosomes 17 and X reveals positions of sequence heterogeneity as two bands at a single nucleotide position on a sequencing ladder. The use of TdT in the sequencing reactions greatly reduces the background associated with polymerase pauses and stops, allowing visualization of heterogeneous bases found in as little as 10% of the repeat units. Confirmation of these heterogeneous positions was obtained by comparison to the sequence of multiple individual cloned copies obtained both by PCR and non-PCR based methods. PCR amplification of alpha satellite can also reveal multiple repeat units which differ in size. Analysis of repPCR products from chromosome 17 and X allows rapid determination of the molecular basis of these repeat unit length variants, which appear to be a result of unequal crossing-over. The application of repPCR to the study of tandemly repeated DNA should allow in-depth analysis of intra- and interchromosomal variation and unequal crossing-over, thus providing insight into the biology and genetics of these large families of DNA. PMID- 1461734 TI - Genetic effects of oxidative DNA damage: comparative mutagenesis of 7,8-dihydro-8 oxoguanine and 7,8-dihydro-8-oxoadenine in Escherichia coli. AB - A single 7,8-dihydro-8-oxoguanine (G8-OXO; 8-hydroxyguanine) adduct in the lacZ alpha gene of bacteriophage M13 DNA induces a targeted G-->T transversion after replication in Escherichia coli (Biochemistry, 29, 7024-7031 (1990)). This mutation is thought to be due to the facile formation during DNA synthesis of a G8-OXO.base pair, where G8-OXO is in the syn conformation about the deoxyglycosyl bond. A related modified purine, 7,8-dihydro-8-oxoadenine (A8-OXO; 8 hydroxyadenine), is an abundant product found in irradiated and oxidized DNAs. Similar to G8-OXO, as a mononucleoside A8-OXO assumes the syn conformation. This work has assessed the relative mutagenicities of A8-OXO and G8-OXO in the same experimental system. A deoxypentanucleotide containing A8-OXO [d(GCT-A8-OXOG)] was synthesized. After 5'-phosphorylation with [gamma-32P] ATP, the oligomer was ligated into a duplex M13mp19-derived genome at a unique NheI restriction site. Genomes containing either A8-OXO (at position 6275, [+] strand) or G8-OXO (position 6276) were denatured with heat and introduced into E.coli DL7 cells. Analysis of phage DNA from mutant plaques obtained by plating immediately after transformation (infective centers assay) revealed that G8-OXO induced G-->T transversions at an apparent frequency of approximately 0.3%. The frequency and spectrum of mutations observed in DNA sequences derived from 172 mutant plaques arising from the A8-OXO-modified DNA were almost indistiguishable from those generated from transfection of an adenine-containing control genome. We conclude that A8-OXO is at least an order of magnitude less mutagenic than G8-OXO in E.coli cells with normal DNA repair capabilities. PMID- 1461737 TI - Heterochromatin protein 1, a known suppressor of position-effect variegation, is highly conserved in Drosophila. AB - The Su(var)205 gene of Drosophila melanogaster encodes heterochromatin protein 1 (HP1), a protein located preferentially within beta-heterochromatin. Mutation of this gene has been associated with dominant suppression of position-effect variegation. We have cloned and sequenced the gene encoding HP1 from Drosophila virilis, a distantly related species. Comparison of the predicted amino acid sequence with Drosophila melanogaster HP1 shows two regions of strong homology, one near the N-terminus (57/61 amino acids identical) and the other near the C terminus (62/68 amino acids identical) of the protein. Little homology is seen in the 5' and 3' untranslated portions of the gene, as well as in the intronic sequences, although intron/exon boundaries are generally conserved. A comparison of the deduced amino acid sequences of HP1-like proteins from other species shows that the cores of the N-terminal and C-terminal domains have been conserved from insects to mammals. The high degree of conservation suggests that these N- and C terminal domains could interact with other macromolecules in the formation of the condensed structure of heterochromatin. PMID- 1461736 TI - The histone mRNA 3' end is required for localization of histone mRNA to polyribosomes. AB - The final step in mRNA biosynthesis is transport of the mRNA from the nucleus to the cytoplasm. Histone genes from which the 3' stem-loop has been deleted are transcribed to give RNAs with heterogeneous 3' ends. These RNAs are localized in the nucleus and are stable. Addition of the histone 3' processing signal either on short (< 250 nts) or long (> 1000 nts) transcripts restores 3' processing and transport of the mRNA to the cytoplasm. In addition chimeric histone-U1 snRNA genes which produced RNAs with either histone or U1 3' ends were analyzed. Transcripts which ended with U1 snRNA 3' ends were not efficiently localized to polyribosomes. However, transcripts containing the same sequences including the snRNA 3' end followed by the histone 3' end were present in the cytoplasm on polyribosomes. Taken together these results suggest that the histone 3' end is required for export of histone mRNA to the cytoplasm and association of the mRNA with polyribosomes. PMID- 1461738 TI - Inactive O6-methylguanine-DNA methyltransferase in human cells. AB - A plasmid encoding a recombinant human O6-methylguanine-DNA methyltransferase (MGMT) fused to a fragment of the bacteriophage lambda N protein has been constructed. The fusion protein retained methyltransferase activity when expressed at high levels in E.coli and was purified to essential homogeneity by a simple procedure. Antisera raised against the purified fusion protein recognized MGMT in western blots of extracts of human cells. For most cell lines, there was a quantitative relation between the amount of immunologically detectable MGMT protein and enzyme activity. However, four cell lines contained detectable MGMT protein despite having no measurable methyltransferase activity. Additionally, a HeLa line contained considerably more immunoreactive MGMT protein than could be accounted for by its methyltransferase activity. Thus, some cells contain significant amounts of inactive MGMT. Preliminary characterization of the inactive protein in HeLaS3 cells indicated that it has some properties in common with MGMT methylated at the active cysteine residue. PMID- 1461739 TI - In vivo specificity of EcoRI DNA methyltransferase. AB - The EcoRI adenine DNA methyltransferase forms part of a bacterial restriction/modification system; the methyltransferase modifies the second adenine within the canonical site GAATTC, thereby preventing the EcoRI endonuclease from cleaving this site. We show that five noncanonical EcoRI sites (TAATTC, CAATTC, GTATTC, GGATTC and GAGTTC) are not methylated in vivo under conditions when the canonical site is methylated. Only when the methyltransferase is overexpressed is partial in vivo methylation of the five sites detected. Our results suggest that the methyltransferase does not protect host DNA against potential endonuclease-mediated cleavage at noncanonical sites. Our related in vitro analysis of the methyltransferase reveals a low level of sequence discrimination. We propose that the high in vivo specificity may be due to the active removal of methylated sequences by DNA repair enzymes (J. Bacteriology (1987), 169 3243-3250). PMID- 1461740 TI - Nucleotide sequence of the Borrelia burgdorferi rpmH gene encoding ribosomal protein L34. PMID- 1461742 TI - Relationship of DNA-transfer-systems: essential transfer factors of plasmids RP4, Ti and F share common sequences. PMID- 1461741 TI - Nucleotide sequence and secondary structure of 5.8S rRNA from the unicellular green alga, Chlorella ellipsoidea. PMID- 1461743 TI - Nucleotide sequences of the internal transcribed spacers and 5.8S rRNA gene in Canella winterana (Magnoliales; Canellaceae). PMID- 1461744 TI - The high level streptomycin resistance gene from Streptococcus pneumoniae is a homologue of the ribosomal protein S12 gene from Escherichia coli. PMID- 1461745 TI - Nucleotide sequence of the phage T5 DNA segment containing six tRNA genes. PMID- 1461746 TI - The complete nucleotide sequence of hepatitis B virus, subtype adr (SRADR) and phylogenetic analysis. PMID- 1461747 TI - Cyclic AMP response element binding protein CREB and modulator protein CREM are products of distinct genes. PMID- 1461748 TI - Efficient joining of large DNA fragments for transgenesis. PMID- 1461749 TI - Enhanced expression of recombinant proteins in insect cells using a baculovirus vector containing a bacterial leader sequence. PMID- 1461750 TI - An easy and fast alternative to plasmid shuffling for the identification of in vitro mutagenized alleles of essential genes of Saccharomyces cerevisiae. PMID- 1461751 TI - A simple and efficient protocol for isolation of high molecular weight DNA from filamentous fungi, fruit bodies, and infected plant tissues. PMID- 1461753 TI - Imagine. PMID- 1461754 TI - Partnerships: an alternative to rugged individualism. PMID- 1461752 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1461755 TI - AIDS prevention for women: a community-based approach. PMID- 1461756 TI - Holding the Mississippi River in place and other implications for qualitative research. AB - Holding back a river is used here as a metaphor and five suggested "tributaries" are suggested with the purpose of acknowledging the situated context that qualitative nurse researchers may wish to journey upon. Our nursing knowledge base must include the human experience. We need to become oriented to a world of meaning. Meaning will enlighten and give direction to our nursing practice. The unexamined taken-for-granted approach misses the essential structures of being. Those essential structures of being are what might actualize the possibilities of new ideas, new directions, new designs, new life, birth. PMID- 1461757 TI - Pain management as a clinical challenge for nursing administration. PMID- 1461758 TI - The relationship of energy expenditure to physical and psychologic symptoms in women at midlife. PMID- 1461759 TI - AAN Expert Panel Report. Culturally competent health care. PMID- 1461760 TI - Who am I and why am I here? PMID- 1461761 TI - Myths, monsters, and magic: personal perspectives and professional challenges of survival. PMID- 1461762 TI - Love and work: oncology nurses' view of the meaning of their work. AB - Phenomenological interviews with 23 nurses and more than 200 hours of participant observation on units of one cancer hospital were conducted to obtain a better understanding of how nurses caring for patients with cancer view their work. When asked to discuss a "critical incident" that captures the essence of oncology nursing for them, most nurses described acute physiologic emergencies. A few nurses described psychosocial needs and explained how they had helped or were unable to help patients and families deal with these needs. A major theme in these incidents was how they related to the nurses' own lives. These findings suggest the need to provide nurses with support and an opportunity to discuss their work. Oncology nurses appear to be motivated by a deep concern for patients and families that creates tremendous stress when conditions such as poor staffing, excessive use of registry nurses, and unexpected crises occur. The task orientation of these nurses also seems to be based on their fundamental concern for patient welfare. PMID- 1461763 TI - The role of the self in adjustment to cancer in elderly women. AB - One way that people may adjust to illness is through a redefinition of the self, especially with respect to the relationship between ideal self and actual self. To investigate psychological adjustment in community-dwelling elderly women, women with cancer (n = 17) were compared to women with other health problems (n = 30) based on measures of psychological distress and well-being, actual self, ideal self, and the discrepancy between actual self and ideal self. Women with cancer scored no differently than other women on measures of psychological well being, psychological distress, and actual self, but their ideal-self ratings were lower. The positive adjustment of women with cancer may be the result of their ability to lower their ideal-self expectations, thereby reducing self discrepancies that can result in psychological distress. PMID- 1461764 TI - Psychosocial functioning of adolescents with cancer: a developmental perspective. AB - This literature review summarizes research conducted over the past 25 years that investigated the psychosocial functioning of adolescents with cancer. The research is divided into two conceptual areas that have been investigated by researchers in the disciplines of medicine, psychology, and nursing. One area is the impact of cancer on developmental processes in the adolescent period, and the second area is coping strategies and styles of adolescents with cancer. Studies examining the effects of cancer on the adolescent's self-esteem, general psychosocial development, and perception of control also have been included. The article concludes with a summary of findings, suggestions for future research endeavors, and implications for nursing practice. PMID- 1461765 TI - Failure to master early developmental tasks as a predictor of adaptation to cancer in the young adult. AB - The ability of young adults to adapt to living with a cancer diagnosis and to negotiate the healthcare system is influenced by their level of maturity. If adolescent developmental tasks have been unresolved or pathologically resolved, they are likely to be reenacted during the various stages of the malignancy. Retrospective review of case histories that illustrate the diverse ranges of adaptation to life-threatening illness indicates that success or failure in achieving ego autonomy and continuity in adolescence significantly influences the young adult's capacity to cope with the malignancy. Psychosocial assessment of the young adult patient and spouse, with attention to childhood, adolescent, and family history, will assist the oncology nurse in predicting the individual's capacity for adapting to the illness and complying with treatment. This developmental information will allow clinicians to modify interventions to compensate for earlier stage deficits. PMID- 1461766 TI - Consent forms: how to determine and improve their readability. AB - This study investigated the reading level estimates of cancer clinical trial consent forms from actively accruing studies at the Medicine Branch and the Clinical Pharmacology Branch of the National Cancer Institute. Forty-four consent forms were analyzed using the SMOG formula. Readability levels ranged from grade 12 to grade 17.5 (mean = 14.3). The conclusion was that these consent forms were written above most subjects' reading levels. The usefulness of consent forms could be improved significantly by using readability formulas, applying rewriting techniques, and being aware of subjects' comprehension levels. This paper suggests a number of strategies that nurses can use to enhance comprehension of the information contained in informed consent documents. PMID- 1461767 TI - Analgesic decision-making skills of nurses. AB - Administration of analgesics is a common nursing intervention for providing pain relief to patients with cancer. A sample of 177 nurses participated in a study to examine their decision-making skills when analgesic orders were changed. Nurses were given four clinical vignettes and reference materials to assist them in responding to the vignettes. Twenty-six percent of 708 responses provided by the nurses were answered correctly. Twenty-nine percent of the sample answered all four vignettes incorrectly. The majority (44%) answered only one vignette correctly. No statistically significant differences were found between correct answers and type of work setting, academic preparation, number of patients with cancer cared for per week, number of years employed as a nurse, recent clinical experience with the analgesics used in the vignettes, or the use of reference materials. These findings raise concerns that patients requiring analgesics may not receive an amount that adequately relieves their pain or avoids unnecessary toxicity. PMID- 1461768 TI - Patient education for fatigue. AB - Although fatigue is a frequent complaint of patients undergoing cancer treatment, specific self-care activities are seldom addressed in patient education materials. To fill this void, a patient education tool was developed, with a special emphasis on the management of fatigue. Testing is under way with a large population of patients with cancer. PMID- 1461769 TI - Oncology Nursing Society Life Cycle Task Force report: the life cycle of the oncology nurse. PMID- 1461770 TI - Maternity nursing pads prevent mastectomy wound leakage. PMID- 1461771 TI - Simple solution minimizes problems with i.v. controllers. PMID- 1461772 TI - Opioids may cause assumed disease side effects. PMID- 1461773 TI - Risk of needle-stick during port decannulation reduced. PMID- 1461774 TI - Steps recommended to minimize skin ulceration from mitomycin-C. PMID- 1461775 TI - [Physiology of pubertal maturation]. AB - Most important features of puberty are described. The puberty is the age of development of sexual characters. In females it appears between 10 and 15 years +/- 1 year whereas in males signs of puberty are visible between 11 and 15 years. In our country menarche appears at the mean age of 12 years and 2 months +/- 1 year and 2 months. Precocious puberty in females is that which appears before 8 years and 6 months and in males before 10 years. Delayed puberty is that which appears in females after 15 years and in males after 16. Nowadays is possible to keep off puberty when it is too soon by means of an analogous of LH-RH and as the result the subject reaches a better statural growth. The puberty should not be confused with the adolescence which is characterized by psycho-social maturity. PMID- 1461776 TI - [Von Willebrand's disease]. PMID- 1461777 TI - [Physiopathologic and therapeutic aspects of persistent fetal circulation. Review of the literature and personal histological observations]. AB - Persistence of the fetal circulation (PFC) is a syndrome characterized by failure of the cardiocirculatory system to adapt successfully to postnatal life. Its typical feature is persisting right-left shunt across fetal channels which determines cyanosis refractory to oxygen treatment. PFC can simulate cyanotic congenital cardiopathy. It has two forms: a primitive form and secondary one due to various causes especially perinatal asphyxia. Both forms have a common pathogenesis consisting of hypertension of the pulmonary arterial circulation. This article reviews the physiology of the main prenatal and postnatal circulatory characteristics and the factors which regulate the pulmonary circulation. It also reports the latest findings on PFC physiopathology and treatment indicating the prognostic factors and future perspectives. PMID- 1461778 TI - [Fever as periodic disorder]. AB - Slight, moderate but also high rises in temperature, excluding other causes of fever, can be considered symptoms of periodic syndrome originating by hypothalamic centers as soon as headache, recurrent abdominal pains, growing pains, dizziness, kinetosis. These rises aren't uncommon, but often aren't considered important and this few statistics are available. The Authors present 16 case reports of fever as periodic symptom and discuss how common factors exist in the mechanism of hyperthermia and other clinical signs of periodic syndrome (ex. migraine) but they are generally modulated differently so that disturbance of temperature regulation predominates in the first case, pain in the second. PMID- 1461779 TI - [Neuropsychologic development of small for gestational age preterm infants: follow up at 12-36 months of age]. AB - We followed 94 preterm infants (G.A. < 37 weeks) small for gestational age (SGA) born from 1980 to 1987 in Pavia and admitted to the Neonatal Intensive Care Unit of S. Matteo Hospital (Pavia). A control group matched for gestational age of 94 preterm appropriate for gestational age (AGA) was also studied. Neurological examination was carried out at 40 weeks postmenstrual age and at 3, 6, 9, 12, 24, 36 months of age with the method of Amiel-Tison and Grenier (1986). Psychomotor development was assessed using Brunet-Lezine's Scale until 1985 and after Bayley Scales of Infant Development. Intrauterine mortality was 23.40% in the SGA group and 5.32% in the AGA group (p = 0.0003); neonatal mortality was 18% in the SGA group and 6.62% in the AGA group (p < 0.01). 42 SGA (80.8%) and 58 AGA (79.5%) were completely normal (group A) at 36 months, but SGA infants showed transient neurological abnormalities (TNA) more frequently than the control group (30.7% vs 6.8% - p < 0.001). 5 SGA (9.6%) and 10 AGA (13.7%) had minor abnormalities (group B); no SGA children and only one AGA had diplegia (group C); 3 SGA (5.8%) and 4 AGA (5.5%) were considered to have severe handicap (group D) SGA children had a higher incidence of epilepsy (3.8% vs 0) than AGA (group E). These results show that in our group of SGA preterm infants the union of intrauterine growth retardation and prematurity compromise the possibility of survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461780 TI - [Neuropsychological follow-up of children with phenylketonuria treated early]. AB - We evaluated, yearly, the neuro-psychological development in 16 out of the 27 children with phenylketonuria detected via neonatal screening in the years 1980 90. 14 children had the classical form, while 2 had "variant" type of phenylketonuria. Development quotients always were slightly lower in patients than in controls, but the greatest difference was seen at 1 year of age (92.5 +/- 6.7 vs 101.6 +/- 2.2). At age 6 years, 4 children out of 11 had a IQ equal or below 90.2 of them had neonatal asphyxia, while the others showed, after age 2-4, constantly elevated phenylalanine levels. Four children had a bad metabolic control, as from the age of 2-4 year, and only 1 of them showed a normal IQ at 6 years of age. Regression analyses were used to determine the best predictors of IQ. Parents' social level stood out as the best predictor of IQ at 6 years of age. If this parameter was excluded, phenylalanine level, especially at age 4, best predicted IQ. The following variables had no influence: age at start of diet (they were all begun on diet within the first month of life), pre-diet phenylalanine levels and phenylalanine levels at 1 year of age (all children were, at this age, on good control), DQ (Development Quotient) at age 1. A high percentage (10 out 14) of hyperactive and psychologically instable children was also found, but with no correlations with IQ levels. PMID- 1461781 TI - [Rheumatic fever from 1960's to 1990's. Case records in 2 hospitals of the Lombardian area]. AB - An epidemiological study of rheumatic fever (RF) has been done. Incidence and prevalence of RF observed in Monza Hospital from 1964 to 1990 and in Como Hospital from 1980 to 1990 both show a progressive reduction. An exception to this trend was observed in 1986 in Monza in 1985 in Como. The percentage of carditis in pediatric age is high (60-70%), often associated with arthritis and chorea. However carditis clinical picture seems nowadays less severe, probably because in the past the diagnosis was delayed. Sice 1980 no death were observed due to RF or related cardiac involvement. Relapses and residual valvulopathies are significantly reduced only when penicillin prophylaxis was correctly performed. PMID- 1461782 TI - [A comparative study of 3 different types of trivalent measles-mumps-rubella vaccine]. AB - The results of a randomized double blind comparative clinical trial are described. 201 children, 101 males and 100 females, average age 3.11 +/- 1.1 (range 15 months to 14 years) received 3 different types of triple vaccine against measles, mumps and rubella. The vaccine containing the strains Edmonston Zagreb, Rubini and Wistar Ra 27/3 was well tolerated both for the number of side effects and for the number and the level of the fever attacks, that resulted the most frequent symptom, especially in the children from 2 to 5 years. The differences between side effects were highly significant. In accordance with the obtained results and considering the data of other studies, the Authors conclude that the principal reason of this tolerance is due to more attenuated strain against measles. PMID- 1461783 TI - [Edema in acute diffuse glomerulonephritis, rheumatic peliosis and epidemic parotitis]. AB - The Authors present a substantial series of infant APING in which the venous blood gas analysis shows poor use of oxygen, due to a probably reduced cellular combustion associated with low pCO2, high pH, which are characteristic of arterial blood travelling through anastomotic paths and preferential channels at the microcirculation level. They emphasize the contemporaneous increase in volemia, even with oedema present, and the poor permeation of the capillary wall found with the Landis test, contrary to what happens in glomerulonephrosis with minimal changes which features increased systematic capillary permeation with hypovolemia. The look of the oedema, together with the hypervolemia, led to the suspicion that the nephritic oedema was a sign of mainly intracellular oedema. In the opinion of the Authors these nephritic forms would seem to show systemic cellular respiratory suffering sensitive to the action of chlorpromazine, which has also dealt swiftly and cleanly with the oligoanuresis. The Authors consider 52 cases of Schoenlein-Henoch vasculitis which showed very rapid detumescence of periarticular swelling and those on the back of the hands and feet, as well as the disappearance of skin petechias and melena following treatment with chlorpromazine. They also mention two cases of Kawasaki's disease which seemed to react favorably to the combination of the action of chlorprmazine with acetylsalicylic acid. The effects obtained with chlorpromazine in 27 cases of epidemic parotitis with periscialoadenitis elastic tumescence are reported, with the focus on the reduction of the perisalivary tumescence. It is important to point out the very rapid disappearance of epigastrial pain, probably pancreatic in origin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461784 TI - [Evaluation of blood sugar self-monitoring of diabetic children and its educational applications]. AB - In diabetics children's education is important to "make" information, but it's important also to verify whether informations are given correctly. By use of computerized system it's possible to control the quality of self-management (number of glycemias, change in doses of insulin, values of HbA1c) and to determine the "know" and the "know how". PMID- 1461785 TI - [Hypertrophic pyloric stenosis in infants. A retrospective study of cases observed in the years 1970-1990]. AB - Although the definitive cause of infantile hypertrophic pyloric stenosis is unknown, it's probable that several predisposing risk factors would be associated with the condition. We analysed some perinatal factors in relation to the incidence of infantile hypertrophic pyloric stenosis among children observed during the period 1970-90. We examined 61 infants with surgically confirmed hypertrophic pyloric stenosis and, as controls, 61 healty children comparable for age. In every child we studied: sex, birth rank, pregnancy and delivery, birthweight, parental age, type of feeding, familial history of hypertrophic pyloric stenosis and of atopy, seasonal variation in incidence, AB0 and Rh blood phenotypes. In the 61 infants with hypertrophic pyloric stenosis, the incidence of three factors (male sex, primogeniture and feeding with artificial milk) was significantly higher than that in the controls. We conclude that infantile hypertrophic pyloric stenosis probably has a particular genetic basis, but perinatal factors are responsible for the rising of the condition. However the true aetiology remains to be elucidated. PMID- 1461786 TI - [Comparison of plasma concentrations of amoxicillin administered by oral and venous routes in neonatal bacterial colonizations]. AB - The amoxicillin is a drug that for the incomplete capacity of intestinal absorption in newborn is give for intravenous way. The use of this way and the duration of treatment impose the separation of the newborn from mother and a proportionate preparation of the nurses for the execution of this therapy. We have compared, in newborn infants, with clinical and laboratory diagnosis of neonatal infection, the amoxicillin's plasmatic concentration after intravenous giving and oral giving, in relation to minimum inhibiting concentration the bacteria cause of neonatal infections. In our study (duration 10 months) the newborn infants were perfectly comparable for gestational age, Apgar's score, birthweight, breastfeeding. The newborn infants, at random, were divided in two groups; the first group (18 newborns) received drug for oral way, the second group (14 newborns) for intravenous way. The dosage was 40 mg/Kg/dose of amoxicillin. The duration of treatment was 4 days. Remarkable was the great individual variability of plasmatic concentration of amoxicillin independently from way of giving. The plasmatic concentrations were nearly similar except for the first half hour (plasmatic concentrations after oral giving was lower). The use of oral way is, therefore, favourable for the facility of giving and effective as the intravenous way in the control of neonatal infections. PMID- 1461787 TI - [A case of diaphragmatic eventration associated with Wolff-Parkinson-White syndrome]. AB - The Authors report a case of diaphragmatic eventration associated with Wolff Parkinson-White's syndrome. It's difficult to explain this unusual association. It's possible that the presence of cardiac accessory pathways in this particular patient is due to the alteration of the normal anatomical relationship resulting from the diaphragmatic eventration. PMID- 1461788 TI - [Neuroblastoma with muscular localization: description of a case]. AB - An unusual case of abdominal neuroblastoma, whose extension involved the psoas muscle, leading to an ultrasonographic and Magnetic Resonance imaging simulating an haematoma, is described. Histology disclosed the malignant nature of the muscle mass. The Authors discuss the value of the new imaging techniques and in particular of Magnetic Resonance in the diagnostic work-up of paediatric malignancies. PMID- 1461789 TI - [Sertoli-Leydig cell tumor with a retiform pattern: description of a case]. PMID- 1461790 TI - [Long-term asymptomatic incubation in vertical HIV infection. Description of a case and review of the literature]. AB - The natural history of HIV infection in perinatally-infected children is still poorly defined; more information about disease progression is needed for the design of clinical and therapeutic trials. According to the most recent reports, vertically-acquired infection seems to follow two different modes of progression, with the majority of patients expressing early signs of severe disease, whereas a subgroup of mildly affected infants has a longer survival, comparable to that previously reported for adults: the long term prognosis of this last patient group remains unknown. Current estimates of incubation periods in children are based on limited data, largely drawn from ill patients: hence subjects with a short incubation time are more likely to be observed. A case is described of a child born in 1982 to an asymptomatic intravenous drug abuser mother. HIV infection was detected in both mother and son only in 1984, but other risk factors for HIV infection of the infant (i.e. blood transfusions, sexual abuse) were excluded. The child had an uneventful neonatal period and childhood, with normal growth and development; up to now, at the age of 9 years 6 months, no clinical signs and symptoms possibly related to HIV infection became evident. Laboratory examinations showed only slight immunologic abnormalities (class P-1 B, CDC), such as increased serum immunoglobulin levels, reduction of CD4+/CD8+ ratio with no relevant decrease of absolute CD4+ lymphocyte count (1100/mm3); HIV p24Ag and virus isolation were always negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461791 TI - [Spondylo-costal dysostosis: presentation of a new case with autosomal dominant heredity and discussion of problems in genetic counseling]. AB - The Authors report a new family with spondylo-costal dysplasia in which three members in three generation are affected. The genetic heterogeneity of the condition and its implication in genetic counseling is discussed. PMID- 1461792 TI - The epidemiology and clinical features of obsessive compulsive disorder. AB - During the past decade, there has been rapid growth in understanding the clinical features, pathophysiology, and treatment of obsessive compulsive disorder (OCD). This article reviews the current state of knowledge of the epidemiology and clinical features of OCD with a focus on the disorder's phenomenologic heterogeneity and its comorbidity with other Axis I and Axis II syndromes. PMID- 1461793 TI - The genetics of obsessive compulsive disorder and Gilles de la Tourette's syndrome. AB - This article reviews the evidence that obsessive compulsive disorder (OCD) and Gilles de la Tourette's syndrome (GTS) are both familial and genetic. Studies are summarized that suggest that (1) some forms of OCD are related to GTS, (2) some forms of OCD are familial and may not be related to GTS, and (3) the patterns of inheritance of GTS and OCD within the same families are consistent with the transmission of an autosomal dominant genetic locus. PMID- 1461794 TI - Childhood-onset obsessive compulsive disorder. AB - The clinical presentation of OCD in children and adolescents is quite similar to that in adults, with overlapping obsessional content and compulsive ritualistic patterns. In addition, both age groups provide essentially identical descriptions of the anxiety accompanying their compulsions and invoke similar mechanisms to resist acting out the ritualistic behavior. Responses to behavioral treatment and pharmacotherapy are similar across ages, and the disorder appears to be chronic and unremitting in the studied populations whether its onset is in childhood or adulthood. Conversely, the strong familial influence, male predominance, neuroendocrine abnormalities, presence of tics and other neurologic abnormalities, and possible impact on personality development suggest that pediatric OCD has important differences from its adult counterpart. Further investigations of these unique features of childhood-onset OCD are warranted and may provide etiologic clues to the disorder. PMID- 1461795 TI - Trichotillomania. An obsessive compulsive spectrum disorder? AB - Trichotillomania is a neglected neuropsychiatric disorder that only recently has received research attention. Based on clinical data, it appears far more common than previously believed. Like OCD, the behavior is recognized as senseless and undesirable, but is chronic and difficult to treat. The comorbidity, drug response data, familiality, and phenomenology of the disorder extend the concept of OCD to a spectrum of inappropriately released, excessive grooming behaviors. Although the discovery of clomipramine's effectiveness has provided relief to some trichotillomanics, further work is indicated to find regimens that provide long-term suppression of symptoms. Ongoing investigations of early-onset trichotillomania may reveal etiologic triggers, whereas studies that examine the similarities and differences between trichotillomania and OCD may help define the neurobiology of OCD, and possibly of other atypical impulse control disorders. PMID- 1461796 TI - Hypochondriasis and obsessive compulsive disorder. AB - Hypochondriasis and OCD differ conceptually in the degree to which the patient's disease concerns are experienced as an intrusive mental event or a reasonable psychological response to a realistic health threat, in the degree to which the ideation is resisted, and in the presence of somatic sensations and medical help seeking. There are, however, some similarities between the conditions, including the development of excessive, stereotyped, repetitive behaviors in an attempt to allay their anxiety. Empirical data on the degree of overlap between the conditions are too limited to permit definitive conclusions. The little that we do know, however, suggests that (1) the prevalence of OCD in hypochondriasis is probably elevated, but not extraordinarily so; (2) the prevalence of hypochondriasis in OCD is unknown; (3) fears about disease, illness, and injury are one of the more common forms of obsessions seen in OCD; and (4) there are several ill-defined and largely unexplored conditions, such as disease phobias, which appear to be very similar to both OCD and hypochondriasis. Clinical experience suggests that there may be a subgroup of hypochondriacal patients who are closer to the anxiety disorders in general and to OCD in particular. This subgroup might respond to the newer, antiobsessional, serotonin reuptake blocking agents. PMID- 1461797 TI - Personality disorders in obsessive compulsive disorder. AB - Standardized structured interview personality scales are now available that provide better reliability than clinician interview, but are still imperfect. These scales diagnose DSM III-R personality disorders, which are more illness oriented than Freudian notions. Use of these scales has found that the majority of patients with OCD have at least one Axis II personality disorder, with most falling in cluster C. Obsessive compulsive personality disorder, as described in DSM-III-R, is, in most samples studied, present in the minority of patients with OCD, and is often less common than other personality disorders such as mixed, dependent, avoidant, and histrionic. The prevalence of this personality disorder as modified in DSM-III-R (making it easier for a patient to qualify for this personality disorder diagnosis) appears to be higher, although still present in a minority of patients with OCD. Obsessive compulsive personality disorder (along with the other cluster B and C personality disorders) has not been reported to have a consistent relation to treatment outcome. There is evidence that in some cases, obsessive compulsive personality disorder may be secondary to OCD. Swedo et al hypothesized that some children may develop compulsive personality traits as an adaptive mechanism to deal with OCD. This hypothesis is in accord with our finding that OCD often predates compulsive personality disorder and that mixed personality disorder may develop over time, possibly secondary to OCD. We found in our sample of 96 adult patients with OCD that the presence of mixed personality disorder was more likely with longer duration of OCD, suggesting that patients who do not have premorbid personality disorders may develop significant personality traits (especially avoidant, compulsive, and dependent), which may be related to behavioral and life-style changes that are secondary to OCD. This hypothesis is strengthened by our finding that patients with one of these personality disorders at baseline tended to no longer meet criteria for them following successful treatment of their OCD. It now appears that schizotypal personality disorder, which is thought to be related genetically to schizophrenia (e.g., in three male identical twin pairs concordant for OCD but discordant for schizophrenia or schizoaffective disorder, the nonpsychotic co-twins all had schizotypal personality disorder), is the only consistent personality disorder predictor of poorer outcome in OCD. These traits may help explain other proposed poor predictors of treatment outcome such as overvalued beliefs, poor compliance, and chaotic family situations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1461798 TI - Neurobiology of obsessive compulsive disorder. AB - In this brief review of two of the neurobiologic aspects of OCD, two simplistic models have been suggested. Although these models reflect different perspectives, they may not be independent. For instance, the striatum, which is a focus for the neuroanatomic model, receives a dense serotonergic projection from the dorsal raphe. Similarly, as mentioned previously, combining PET studies and drug treatment demonstrates that the increased metabolic activity seen in the orbital cortex appears to normalize with serotonin uptake inhibitor treatment. Insights into the neurobiology of this syndrome will require combining perspectives as well as developing additional approaches. In addition, the search for neurobiologic abnormalities must be guided by a continuing regard for phenomenology. There is no reason, a priori, to assume that this syndrome subsumes only one disorder. The careful dissection of subgroups--whether based on symptom type, character style, or comorbid diagnoses--will be increasingly vital for understanding the results of neuropharmacologic and functional imaging studies. PMID- 1461799 TI - Normal and abnormal information processing. A neuropsychological perspective on obsessive compulsive disorder. AB - This article presents a neuropsychological perspective on obsessive compulsive disorder (OCD) and describes some of the cognitive strengths and weaknesses that characterize the disorder. Neuroanatomic findings and theories of the neurologic basis of OCD are reviewed as are studies that use neuropsychological assessments. Findings of frontal lobe and/or basal ganglia dysfunction as well as memory deficits are emphasized. This information is then discussed in the context of cognitive-behavioral and information processing perspectives that emphasize normal patterns in anxiety and worry. The goal is to provide an integrated conceptual model of OCD, identifying the normal and abnormal information processing patterns that characterize the disorder. PMID- 1461800 TI - Tourette's syndrome and obsessive compulsive disorder. Clinical aspects. AB - Tourette's syndrome (TS) is a disorder that typically has its onset in childhood or early adulthood and is characterized by the presence of both motor and vocal tics. Obsessive compulsive symptoms (OCS) frequently occur in patients with tic disorders. The earliest descriptions of TS included obsessive thinking as a part of the symptom complex. Recent studies suggest that obsessive compulsive disorder (OCD) may occur in as many as 7% of patients with TS, and that both of these disorders share a similar clinical phenomenology and familial patterns of transmission. This article explores similarities and differences between these two disorders. PMID- 1461801 TI - Assessment of severity and change in obsessive compulsive disorder. AB - Useful clinician-rated measures of OCD are now available. The Y-BOCS and NIMH Global OC both seem suitable for monitoring outcome in drug trials of OCD. These two scales seem relatively specific for symptoms of OCD and are sensitive to drug induced changes in symptoms. Neither the Y-BOCS nor the NIMH Global OC confuse trait with state. There are ample data suggesting that the Y-BOCS is reliable and valid scale. Unlike some of the symptom inventories, such as the LOI and MOCI, final scores on the NIMH Global OC and Y-BOCS are not influenced directly by the type or number of obsessions and compulsions present. A computer-administered version of the Y-BOCS has been developed. Currently available patient-rated instruments suffer from serious shortcomings, including insensitivity to change and poor representation of patients with mono-symptomatic clinical pictures (e.g., hoarding alone). Some rating scales have been adapted for use in children with OCD. Several groups, including our own, have elected to use change scores on the 10-item Y-BOCS and a global measure of OCD, such as the NIMH Global OC or modified OGI, as the principal outcome variables in drug trials in patients with OCD. Several studies have selected a 35% decrease in Y-BOCS scores from baseline as indicative of clinically significant improvement. A limitation of all single item global measures is that they cannot be resolved into smaller components. The more fine-grained analysis that is possible with the multi-item Y-BOCS makes it more desirable as a primary outcome measure, with a global scale as a secondary outcome measure. PMID- 1461802 TI - Neuroimaging studies of obsessive compulsive disorder. AB - In the last 5 years, there has been an explosion of neuroimaging studies of obsessive compulsive disorder. This work is now beginning to suggest dysfunctional brain regions and circuits that may mediate some of the symptoms of this classic neuropsychiatric illness. PMID- 1461803 TI - Behavior therapy for obsessive compulsive disorder. AB - Behavior therapy for OCD with exposure and response prevention is effective in reducing obsessions and rituals in at least half of those suffering this disabling disorder. Office-based sessions in which patients participate actively in designing exposure and response prevention homework are usually sufficient. Therapist assistance is sometimes needed for those who fail to perform these assignments on their own. Poor compliance, severe comorbid conditions, and CNS depressing drugs can interfere with behavior therapy. Techniques to manage these difficulties, including modifications of behavior treatment and the use of serotonin reuptake inhibiting drugs, can increase substantially the number of patients responsive to behavior therapy. PMID- 1461804 TI - Pharmacologic treatment of obsessive compulsive disorders. AB - Medications are currently available that have been well studied in adequately designed controlled trials that predictably help the majority of obsessive compulsive disorder (OCD) patients. This article reviews the considerable data on the use of these agents in patients with OCD. In addition, an approach to patients with resistant symptoms is presented. PMID- 1461805 TI - Neurosurgical treatment of malignant obsessive compulsive disorder. AB - Although the majority of patients with obsessive compulsive disorder (OCD) respond well to behavioral techniques, pharmacotherapy, or combinations of these two approaches, a small percentage of patients remain refractory and are severely disabled by their symptoms. Such patients may well be helped by neurosurgical interventions. This article reviews the selection guidelines, indications and contraindications, available procedures, probable outcome, hazards involved, preoperative work-up, and the rationale behind neurosurgery in OCD. PMID- 1461806 TI - Radiation sensitization by estramustine studies on cultured human prostatic cancer cells. AB - In low-stage prostatic carcinoma, local cure can be obtained with radiation therapy alone, while in locally advanced disease the chances for cure are less. In this study, we have addressed the question of whether estramustine (EM), the main cytostatic metabolite of estramustine phosphate (Estracyt), may act as a radiosensitizing agent. This drug accumulates in prostatic cancer and has also been shown to arrest cancer cells at metaphase both in vitro and in vivo. The human prostatic cancer cell line DU 145 was grown as cultures monolayer and incubated with EM in concentrations varying from 1 to 20 micrograms/ml. External beam irradiation was performed with doses ranging from 0 to 8 Gy using gamma rays from a 60Co source. Clonogenic cell survival (CS) was used to analyse the radiation sensitizing effect of EM. The radiation dose modifying factor (DMF) at the survival level 0.1 was found to be 0.77 in the presence of EM (5 micrograms/ml), i.e., 23% sensitization was obtained. When irradiating cells at the standard fraction dose of 2 Gy in the absence of EM, 22% of the cells lost their clonogenic ability. In presence of EM (5 micrograms/ml), 2 Gy caused 40% of the cells to lose their clonogenic ability. Thus a radiation sensitizing effect of EM was established in the CS assay. It was also of interest to determine if the radiosensitizing effect of EM could be confirmed in a rapid assay. The rapid fluorescence assay was used to observe early damage of the cells. Results showed that by 2 days after exposure to irradiation a weak tendency towards sensitization was seen, while a clear sensitization was obtained after 4 days. This indicates that the rapid assay might be developed to a predictive assay for detection of the response of primary prostate tumor cells to the radiation sensitizing effect of EM. PMID- 1461807 TI - Assessing cost effectiveness in orthopedic outcome studies. PMID- 1461808 TI - Learning curves or lines? PMID- 1461809 TI - More on ethics. PMID- 1461810 TI - Distal femoral osteotomy for valgus deformity of the knee. AB - Distal femoral varus osteotomy and blade-plate fixation for valgus deformity of the knee proved effective in restoring axial alignment in 18 of 36 knees (34 patients). Patients were followed for an average of 5.4 years (range: 2 to 19 years). The osteotomies were performed on 14 men and 22 women (average age: 44 years; range: 14 to 77). The patients' average preoperative valgus deformity of the anatomical axis was 19.4 degrees (range: 8 degrees to 33 degrees). The surgical procedures performed were a medial closing wedge osteotomy (14 knees) and a lateral opening wedge osteotomy with bone grafting (22 knees). Postoperative correction of the anatomical axis averaged 3.8 degrees valgus (range: 8 degrees varus to 20 degrees valgus). Maximum improvement was reached within 6.3 months by patients who were less than 60 years old and within 5.1 months by patients who were more than 60 years old. Pain decreased or resolved in 21 of 35 knees (60%); activity level improved in 24 of 35 knees (69%). One patient was unavailable for follow up evaluation. Varus osteotomy in the distal femur was concluded to be an acceptable form of treatment in the valgus knee alone or associated with traumatic or osteoarthritis of the lateral compartment. PMID- 1461811 TI - Tinel's sign and Phalen's test in carpal tunnel syndrome. AB - Tinel's sign and Phalen's test are two provocative tests used in the diagnosis of carpal tunnel syndrome. A review of the literature reveals a wide range of sensitivity for these tests. Analyzing the historical data and comparing these to the Tinel's sign and Phalen's test results of 100 individuals without carpal tunnel syndrome (200 wrists), we conclude that the Tinel's sign is not useful in the evaluation of patients with carpal tunnel syndrome, whereas Phalen's test, which has a greater sensitivity and specificity, can be of use. PMID- 1461812 TI - A new scale for the clinical assessment of spinal cord function. AB - The systems currently used for grading the severity of neurologic injuries have serious limitations. The authors have developed a neurologic grading system to assess spinal cord function. This is a new, functionally oriented scale which can be used at the bedside and requires no special tests other than those done in a routine clinical neurological examination. This scale includes assessment of motor and sensory function, rectal tone, and bladder control. A major advantage of this scale is that motor function is assessed on a functional rating system. To evaluate the usefulness of this scheme, patients who have been previously entered into a prospective study on the surgical treatment of burst fractures were re-evaluated. A significant number of patients under our new reclassification system were noted to have had significant improvement which had been overlooked using the Frankel Grade system. The authors conclude that their new spinal cord assessment technique has many advantages and suggest that it be used by spinal cord injury centers. PMID- 1461813 TI - Concomitant injuries of the hip joint and abdomen resulting from gunshot wounds. AB - Septic arthritis is a devastating complication of transabdominal gunshot wounds to the hip. Five patients sustained gunshot wounds to the hip which violated the alimentary tract. Diagnosis was established with plain radiographs in three patients, arthrogram in one patient, and a gastrointestinal series in one patient. Three patients had an exploratory laparotomy with diverting colostomy followed by immediate hip arthrotomy within 24 hours and no joint infections occurred. In the other two patients, hip involvement was identified late after septic arthritis occurred. Early diagnosis, diverting colostomy, and immediate arthrotomy are recommended for gunshot wounds to the hip which involve the alimentary tract. PMID- 1461814 TI - The use of postoperative suction drainage in total hip arthroplasty. AB - Two hundred eight primary total hip arthroplasties were reviewed to evaluate the effect of closed suction drainage. This review included 45 hips in which closed drains were used and 163 hips in which drains were not used. These two groups were compared for possible differences in wound problems, temperature elevations, changes in Hgb/Hct, and the need for transfusions. There was no statistically significant difference in postoperative temperatures or decrease in Hgb. However, there were four superficial wound infections in the drained group and three superficial wound infections in the non-drained group (P < .025). There were no deep infections in either group. These findings suggest closed suction drainage provides no apparent advantage in uncomplicated primary total hip arthroplasty. PMID- 1461815 TI - Lyme disease: an orthopedic perspective. AB - The incidence of Lyme disease is increasing. This spirochetal infection may frequently manifest itself with joint involvement without characteristic dermatologic signs or history of tick bite. Serologic testing remains unreliable. Oral or parenteral antibiotics remain the mainstay of treatment. Chronic arthritis develops in approximately 10% of patients with Stage III disease. Lyme arthritis must be considered in the differential diagnosis of patients with mono- or oligoarticular joint involvement, especially in children and young adults with possible tick exposure. Further advances in antimicrobial therapy and serologic testing are anticipated. PMID- 1461816 TI - Mechanical failure of a Bateman bipolar prosthesis. PMID- 1461817 TI - Hairy cell leukemia affecting the hip joint. PMID- 1461818 TI - Palmaris profundus causing carpal tunnel syndrome. PMID- 1461819 TI - Subungal squamous cell carcinoma of the thumb masked by infection. PMID- 1461820 TI - Patellar tendinitis in the recreational athlete. PMID- 1461821 TI - Subtrochanteric fractures following osteosynthesis of femoral neck fractures with the VLC-femoral system. AB - Twenty-two patients with femoral neck fracture were treated with the VLC (Variable Length Cannulated)-femoral screw system. In four patients, the osteosynthesis had complications with ipsilateral subtrochanteric femoral fractures in relation to the screw holes in the lateral cortex. The problem seemed to be excessive stress on the lateral cortex during insertion of the screws. The method has been abandoned in our department. PMID- 1461823 TI - The Academic Orthopaedic Society: small beginnings. PMID- 1461822 TI - Answer please. Scaphocapitate fracture syndrome. PMID- 1461824 TI - Oxygen saturation during reaming and intramedullary nailing of the femur. AB - Oxygen saturation was monitored during the reaming and intramedullary nailing of 15 femoral fractures (three impending) to assess the relationship between intramedullary reaming and nailing and the production of hypoxemia. There were no statistically significant drops in oxygen saturation during this procedure in either the fractured or intact (impending fractures) femora. PMID- 1461825 TI - Long-term treatment with 1 alpha-hydroxyvitamin D3 with calcium supplement in spinal osteoporotic patients. AB - The long-term effect of 1 alpha-hydroxyvitamin D3 and calcium lactate in osteoporotic patients was evaluated by the bone mineral density (BMD) measured at the distal one third and one sixth of the radius and by the vertebral fracture rate. Forty-five osteoporotic patients medicated for 1 to 13 years (treated group) and 11 osteoporotic patients with no medication for 1 to 3 years (control group) were compared. The BMD of the treated group remained unchanged for the first 4 (one-third site) and 6 years (one-sixth site), followed by significant decreases, whereas that of the control group decreased significantly at the second and third year. The effect on BMD was more prominent in the patients with lower initial BMD. The vertebral fracture rate of the treated group was significantly less than that in the control group at the third year. No serious side effects were recognized. Overall, we believe 1 alpha-hydroxyvitamin D3 with calcium supplement can be considered a safe and effective agent for long-term use in osteoporotic patients. PMID- 1461826 TI - Treatment of multiple pterygium syndrome. AB - Multiple pterygium syndrome is a rare, inherited disorder manifested by growth retardation, facial or genital anomalies, and widespread musculoskeletal deformities. Pterygia are the predominant hallmark of the syndrome. Five children with multiple pterygium syndrome were treated from 1978 to 1987. Treatment involved both upper and lower pterygia and contractures. The results of treatment and modalities used are discussed and a protocol suggested. PMID- 1461827 TI - Percutaneous CT-guided stabilization of complex sacroiliac joint disruption with threaded compression bars. PMID- 1461828 TI - Traumatic fracture-dislocation of the hip in a 2-year-old child. PMID- 1461829 TI - Solid aneurysmal bone cyst. PMID- 1461830 TI - Palmar fasciitis and polyarthritis associated with a malignant neoplasm: a paraneoplastic syndrome. PMID- 1461831 TI - Photoelastic analysis of stress distribution on the tibiofemoral joint after meniscectomy. AB - Three-dimensional photoelasticity models of the knee joints were made of epoxy to observe the change in the status of stresses according to the size of defect in the meniscus. Three kinds of meniscus models were made of rubber. Through axial application of a vertical compressive load of 8 kg, equivalent to the joint reaction of 3000 N in the human knee joint, the patterns of the isochromatic fringes were observed and stresses around the knee joint were analyzed according to the size of the defect in the medial meniscus. Stress was increased in magnitude according to the size of the defect of the meniscus, and was focalized after meniscectomy. In the partial meniscectomy model, the maximum stress concentration point of the removed side migrated to the margin of the same side of the joint. But, in the total meniscectomy model, stresses were markedly increased in magnitude on both sides of joints, and maximum stress concentration points were more centralized. This centralization effect would contribute to the degenerative process of the knee joint after meniscectomy. PMID- 1461832 TI - [Tutoplast-Dura and Zenoderm-Corium implant--materials for tissue replacement. Experimental studies]. AB - The results of experimental studies with the use of two biostatic materials: solvent-preserved human dura mater (Tutoplast-Dura--Pfrimmer-Vigo) and lyophilized porcine dermis (Zenoderm-Corium implant--Ethicon) as prosthesis of deficient, abdominal wall tissue are submitted. The studies were performed on an animal model and consisted on the evaluation of mechanical and biological qualities of the investigated materials as well as their surgical handiness and tissue tolerability. The application of knitted polyester net as a reinforcing agent for both materials was also estimated. Process of incorporation of the prosthetic material was investigated macroscopical at 3, 6 and 12 weeks after the implantation. The experimental trials revealed the usefulness of Tutoplast-Dura and Zenoderm-Corium implant in reconstructive surgery in account of their good biocompatibility and adequate, mechanical properties. It was stated that Tutoplast-Dura was characterized by remarkably better surgical handiness in comparison to Zenoderm-Corium implant. Additional mechanical reinforcement with polyester net was not necessary. PMID- 1461833 TI - [Correlations between the properties and effects of clinical therapy using textile material with antipsoriatic action]. AB - The aim of the study was to design a textile material as a carrier for dermatological drugs. Cotton fabric was chosen for experimentation to be a fibrous support for the system. Additional components were a drug carrier in form of synthetic hydrogel impregnation (partially crosslinked poly(acrylic acid) and a bioactive agent dithranol) dispersed within the gel. The rate of release of the drug from the fibrous system was measured in aqueous media and depended on the concentration of dithranol. The structure and physical properties of the material were designed and controlled in order to ensure the optimal contact with the skin. Clinical studies were carried out with psoriatic patients. The results of the treatment with the textile material containing dithranol were presented using a computer optimalization method. In conclusion it was asserted that this type of textile-based medical device is effective and in many respects more convenient and less troublesome alternative in the treatment of psoriasis as compared to conventional treatments with dithranol suspended in ointments and creams. PMID- 1461834 TI - [Absorption of chitosan applied to polyester discs in rats after implantation]. AB - Experiments have been made on white rats implanting polyester blocks covered with chitosan into the peritoneal cavity and to the abdominal wall skin. Before implantation the material was sterilized with ethylene oxide or radiation. The animals were subjected to autopsy 3, 7, 14, 21, 25, 30, 35, 40, 45, 50, 55 and 60 days after implantation with macroscopic and microscopic evaluation. On the basis of the carried out experiments it was stated that the disintegration of chitosan proceeded not uniformly. The resorption time of chitosan oscillated in the range of 45-60 days and it was accompanied by rather strong specific inflammation process. It was characterized with fibrin effusion and with appearance of multi flapped neutrocytes. Essential distinctions in the resorption process of depending on the sterilization mean of the blocks as well as on the place of implantation were not stated. PMID- 1461835 TI - A new procedure in the surgical treatment of large incisional ventral hernias with the use of Dexon Mesh. AB - A new procedure in the surgical treatment of large incisional ventral hernias is described. It is based on the use of enlarged relaxation incisions of the abdominal fascia on both sides of the hernia to perform a direct suture of the posterior and superficial fascial layer of the hernia defect without tension. Extensive fascial defects after enlarged side relaxation incisions should be reinforced to prevent a weakness of the ventral abdominal wall. The best material may be a resorbable knitted mesh. PMID- 1461836 TI - Activity of glucose-6-phosphate-dehydrogenase enzyme studies in calves with long- survivals with total artificial heart. AB - The research aimed at studying metabolic changes of erythrocytes in the calves surviving for a long period with total artificial heart of BRNO VII type. The authors studied partly the count of erythrocytes, the plasma levels of free hemoglobin and activity of glucose-6-phosphate-dehydrogenase enzyme. The changes found were compared with the levels measured in a group of 10 healthy calves. Constant decrease of erythrocyte count, slightly increased concentration of free hemoglobin in plasma and repeatedly decreased activity of the enzyme studied were found in the group of 4 experimental calves, from the 5th to 17th weeks of surviving. These changes can be explained by a long-term action of mechanical stress on the erythrocytes that pass through the pump of the total artificial heart. The cells damaged mechanically have the decreased energetic metabolism and, consequently, shortened viability. As young healthy animals with normal erythropoiesis which is stimulated by the application of drugs during the experiment are used, compensated anaemia develops, but it is not a limiting factor for the surviving of the calves with total artificial heart. PMID- 1461837 TI - [Effect of re-utilization of cuprophan capillary dialysers with different liquids on their biocompatibility and effectiveness of elimination]. AB - In 22 patients cuprophane capillary dialyzers reutilized in turn with four sets of liquids were used four times (Andante type in 13 and TAF-12 in 9 patients). The degree of biocompatibility and efficiency of elimination of small molecules was evaluated. During four-time reuse of dialyzers reutilized with sodium hypochlorite and with formaldehyde a reduction of intra-dialysis leukopenia, granulocytopenia and thrombocytopenia was not stated in blood of the patients. Activation of the complement system measured with the quantity of decrease of C3c fraction of the complement in the patients blood after 20 minutes of dialysis reduced essentially only at the fourth reuse of dialyzers (p < 0.01). Creatinine clearance measured always one hour after starting of the dialysis, did not change in succeeding reuse of dialyzers. Reutilization of dialyzers with hydrogen peroxide solution and formaldehyde caused essential reduction of ++intra-dialysis leukopenia and neutropenia (p < 0.001). There was lack of changes in ++intra dialysis thrombocytopenia. Activation of the complement system was reduced essentially only after the fourth reuse of dialyzers (p < 0.001), but was also essentially lower (p < 0.05) than with dialyzers reutilized with sodium hypochlorite and with formaldehyde. Creatinine clearance practically did not change and at the fourth reuse of dialyzers it decreased on the average by 1.8%. Reutilization with acetic acid already at the second reuse of dialyzers essential (p < 0.001) and deepened decrease of intradialytic leukopenia and neutropenia and the activation of the complement system in course of succeeding reuses. Intradialytic thrombocytopenia was subjected to vestigal, not essential decrease. Creatinine clearance lowered a little but not essentially. At the fourth reuse of dialyzers it was lower on the average by 3.6% than the initial one. Reutilization with Dialina (stabilized blend of peracetic, acetic acid and hydrogen peroxide solution) caused essential (p < 0.001) and, in course of further reuses, deepening of lowering of intradialytic leukopenia and neutropenia as well as the activation of the complement system already at the second reuse. At the same time at the second and fourth reuse of dialyzers reutilized with Dialina the activation of the complement system was essentially lower than reutilized with the other liquids (p < 0.02). At the fourth reuse intradialytic thrombocytopenia also lowered essentially (p < 0.01). Creatinine clearance lowered a little more than with other liquids and at the second reuse of dialyzers was lower on the average by 5.6%, and at the fourth reuse--by 6.7% in relation to the new dialyzers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1461838 TI - Cysteine regulon of Enterobacteriaceae. PMID- 1461839 TI - [DMD gene--the largest human gene]. PMID- 1461840 TI - [DNA repair enzymes: uvrABC endonuclease of Escherichia coli]. PMID- 1461841 TI - [The SOS system: mutagenic response to DNA damage]. PMID- 1461842 TI - [Nomenclature of glycoproteins, glycopeptides and peptidoglycans]. PMID- 1461843 TI - [Metabolism of phosphatidylinositols and their role in signal transmission in plant cells]. PMID- 1461844 TI - [Beta-N-acetyl-hexosaminidase--the enzyme of Tay-Sachs and Sandhoff diseases]. PMID- 1461845 TI - [Automated methods of image analysis and their use in cell biology]. PMID- 1461846 TI - [Caldesmon--regulator of the smooth muscle contraction and the phenomena of the movement of non-muscle cells]. PMID- 1461847 TI - [Regulation of cell cycle--continuation of its history and complications]. PMID- 1461848 TI - End stage renal disease in sickle cell disease: future directions. PMID- 1461849 TI - Leg ulceration in venous disease. AB - We have given a brief summary of the scale of the problem caused by venous ulceration in the UK, and have then reviewed the various theories of causation, including a historical survey, and presented the evidence for and against the two main current theories of fibrin cuffs and white cell trapping. We also outline previous hypotheses of the aetiology of venous ulceration, including arteriovenous microanastomoses, stasis and oedema. The contribution of superficial venous incompetence in the pathogenesis of ulceration is also examined. PMID- 1461851 TI - Intracerebral haemorrhage after thrombolytic therapy for acute myocardial infarction. AB - Seven cases of intracerebral haemorrhage were identified following the use of thrombolytic therapy in a total of 710 patients with acute myocardial infarction. Each case was reviewed in detail with particular attention to the presenting symptoms. A confusional state was the commonest initial feature. Increased age and male sex were associated with increased risk of cerebral bleed. The possible role of intravenous heparin in increasing risk and the management of affected cases is discussed. Early recognition and action is emphasized. PMID- 1461852 TI - Severity of alcoholic liver disease and markers of thyroid and steroid status. AB - Alcoholic liver disease is associated with abnormalities in circulating levels of thyroid, adrenal and gonadal steroid hormones. The relative importance of ethanol consumption and severity of liver disease in the aetiology of these changes and their relationship to clinical abnormalities are unclear. We studied 31 subjects with alcohol-induced liver disease divided into three groups according to the severity of histological features: fatty change, hepatitis and cirrhosis. Circulating concentrations of thyroid, adrenal and gonadal steroid hormones, together with their major binding proteins, were measured in all subjects, and changes related to histology and tests of liver function, as well as clinical endocrine status. A reduction in circulating free tri-iodothyronine (fT3) was seen in subjects with alcoholic hepatitis and cirrhosis, in association with normal or reduced levels of thyrotrophin (TSH). The absence of abnormalities in subjects with fatty change despite similar ethanol intake to the other groups, and correlations between fT3 and liver function tests, suggest that changes in fT3 reflect the severity of underlying liver disease. Similarly, marked increases in circulating cortisol in the hepatitis and cirrhosis groups, and correlations between cortisol and liver function, suggest that changes largely reflect hepatic disease. The absence of clinical features of hypothyroidism or Cushing's syndrome in these groups, despite abnormalities of fT3 and cortisol, suggest an altered tissue sensitivity to hormone effects. In contrast, increases in circulating oestradiol and reductions in testosterone were found in all three groups in males. These findings suggest that both direct effects of ethanol and hepatic dysfunction determine changes in gonadal steroids in males. PMID- 1461853 TI - A randomized trial of one versus three doses of Augmentin as wound prophylaxis in at-risk abdominal surgery. AB - In a randomized prospective trial of prophylactic antibiotics in at-risk abdominal surgery, one dose of intravenous Augmentin (amoxycillin 250 mg and clavulanic acid 125 mg) on induction has been compared with three 8 hourly doses in 900 patients. Wound infection rates which included minor and delayed infections were very similar in those given one dose: 48/449 (10.7%) compared with those given three doses: 49/451 (10.9%) 95% confidence limits - 4.25% + 3.9%. There were more septic and sepsis-related deaths in those patients given one dose (14 deaths) than in those given three doses (7 deaths) P > 0.1 95% CL - 0.4% + 3.0%. However, there were more very elderly patients in the one dose group: 64% of the deaths were aged over 80 and all but one had an emergency operation. There was no difference in the other outcome measures studied which included non-fatal deep sepsis, length of postoperative hospital stay, duration of postoperative fever or the use of antibiotics for postoperative infection. One dose of a suitable intravenous antibiotic gives prophylaxis against wound infection in at-risk abdominal surgery which is at least as effective as multiple doses. However, there may be a risk of overwhelming systemic sepsis in very elderly patients having emergency surgery. PMID- 1461854 TI - Patient recovery following cholecystectomy through a 6 cm or 15 cm transverse subcostal incision: a prospective randomized clinical trial. AB - The effect of incision length on patient recovery following cholecystectomy has not been investigated previously. In this study, 30 patients with symptomatic gallstones were randomized to cholecystectomy through a 6 cm or 15 cm transverse subcostal incision. Postoperative hospital stay was significantly shorter in the 6 cm incision group (median 3 days vs 5 days; P = 0.0069 Mann-Whitney U-test). In the 6 cm group analgesic requirements were reduced (median 2.5 vs 4.5 intramuscular opiate injections per patient) and recovery of depressed postoperative pulmonary function (FVC and FEV1) was faster (3% difference between groups on day 1 and 7% on day 3), although these differences did not achieve statistical significance. These results suggest that the length of incision may influence patient recovery following elective cholecystectomy. This has important implications as surgery carried out through shorter and less traumatic incisions may offer a cost-effective alternative to laparoscopic cholecystectomy. Moreover, some surgeons may find mini-laparotomy cholecystectomy easier to adopt than laparoscopic techniques. PMID- 1461850 TI - Accident and emergency medicine--II. PMID- 1461855 TI - Neuromuscular disease, respiratory failure and cor pulmonale. AB - Respiratory muscle weakness is an uncommon cause of chronic respiratory failure and a rare cause of cor pulmonale. The problem may not be apparent unless specific physical signs are sought or appropriate investigations performed. We present three patients who presented diagnostic difficulty for prolonged periods until the presence of respiratory muscle weakness was considered. Once the diagnosis was established treatment with nocturnal nasal intermittent positive pressure ventilation produced a dramatic improvement in symptoms and allowed a return to a near normal lifestyle. PMID- 1461856 TI - Safety of anticoagulation in the elderly: reasons for discontinuing therapy. AB - We have conducted a retrospective study on the reasons for discontinuing anticoagulants in 50 patients over the age of 75 years compared with 198 adults under 75 years to determine the safety of therapy in the elderly. Venous thromboembolism and arterial embolization were the most common indications for therapy in the elderly and the median duration of therapy in all patients was 7 months (9 days-22 years). There were no deaths attributable to anticoagulants. There was no significant difference in the proportion of elderly patients who stopped treatment because of bleeding compared with 198 patients under 75 years (5/50 (10%) vs 12/198 (6.1%), P = 0.26), nor in the rate of bleeding between the two groups (5/52.5 (9.5%) treatment-years vs 12/249 (4.8%) treatment-years, P = 0.15). This complication rate does not suggest that age per se is a risk factor in the use of oral anticoagulants. PMID- 1461857 TI - Craniospinal intradural arachnoid cyst. AB - A patient with an uncommonly situated congenital intradural arachnoid cyst is reported. The cyst extended from the cervical spinal canal into the posterior cranial fossa and was posterolateral to the spinal cord. The patient's initial complaint was urinary hesitancy. The location of the cyst is unique and the presenting complaint rare. PMID- 1461858 TI - Idiopathic hypereosinophilic syndrome presenting as childhood hemiplegia. AB - A case of childhood hemiplegia due to idiopathic hypereosinophilic syndrome is reported. There was no cardiac lesion. The neurological complications associated with hypereosinophilic syndrome and the pathophysiological mechanism of neurotoxicity of human eosinophils are discussed. It is likely that the neurological deficit was due to eosinophilic neurotoxicity. PMID- 1461860 TI - Biliary peritonitis secondary to perforation of common bile duct: an unusual presentation of chronic calcific pancreatitis. AB - Common bile duct perforation causing biliary peritonitis is an unusual entity and a pancreatic calculus causing this perforation is all the more rare, and to our knowledge has not been reported previously. Such an unusual presentation of chronic calcific pancreatitis is herein reported. PMID- 1461859 TI - Brucellosis with nephrotic syndrome, nephritis and IgA nephropathy. AB - A patient with systemic brucellosis due to Brucella melitensis had severe renal involvement. Clinical features included hypertension, macroscopic haematuria, massive proteinuria of 10 g per 24 hours and azotaemia. Following treatment with antibiotics, the azotaemia resolved and proteinuria decreased to less than 0.5 g per 24 hours, but microscopic haematuria and hypertension persisted. Renal biopsy during recovery revealed IgA nephropathy with minimal mesangial changes, suggesting a causal relation between brucellosis and IgA nephropathy with a reversible nephrotic syndrome. PMID- 1461861 TI - Diagnosis and treatment of lymphomatoid granulomatosis. PMID- 1461862 TI - Intrapericardial phaeochromocytoma associated with two intercarotid paragangliomas: diagnostic considerations. PMID- 1461863 TI - Hypoglycaemia masquerading as a stroke. PMID- 1461864 TI - Acute facial nerve palsy in association with acoustic neuroma. PMID- 1461865 TI - Why test antiplatelet therapy in acute ischaemic stroke and how can this be done? AB - Stroke is a major public health problem, yet there is no treatment of proven value for widespread use in the acute phase of the illness. This paper outlines the rationale for using antiplatelet therapy in acute ischaemic stroke and why it appears to be one of the most promising agents for testing in very large scale clinical trials. PMID- 1461866 TI - Optimization of the blood for oxygen transport and tissue perfusion in critical care. AB - In present practice, patients in intensive care are managed with subnormal haematocrit values and oligovolaemia. Optimization of the blood for oxygen transport in preterm infants in intensive care yields major benefits in their prognosis. A rational basis is described for this optimization in terms of the circulating blood volume and haematocrit, represented by circulating red cell volume (mass). Extrapolation of these lessons in haematological management is proposed for adult patients in critical care, so as to reduce dependence on respiratory support and minimize clinical complications and costs. PMID- 1461867 TI - The use of dobutamine stress thallium scintigraphy in the diagnosis of syndrome X. AB - Dobutamine stress thallium scintigraphy is a non-exercise stress technique used in the assessment of myocardial ischaemia. Non-exercise techniques are independent of the patient's exercise capacity or the subjective development of limiting symptoms. Preliminary data are presented regarding the effects of graded infusions of dobutamine (maximum 20 micrograms/kg/min) in seven consecutive patients with syndrome X. The dobutamine stress test caused significant increases in mean heart rate (rest 65.4 beats/min, peak dobutamine infusion 112.4 beats/min, P < 0.001) and systolic blood pressure (rest 138.6 mmHg, peak dobutamine infusion 166.7 mmHg, P = 0.002) and provoked typical symptoms in all the patients. Single photon emission computerized tomography was performed and the mean number of reversible defects was 1.86 per patient (range 1-3). One patient developed transient atrial fibrillation during the dobutamine infusion but there were no complications in the remainder of the study group. It is concluded that dobutamine-thallium scintigraphy in patients with syndrome X is safe, reproduces patients symptoms' reliably and presents a controllable degree of stress to the cardiovascular system. The consistent demonstration of a reversible perfusion defect in patients with syndrome X is evidence of abnormal myocardial physiology. This criterion could be added to those currently used to define syndrome X in order to improve objectively the identification of this patient group. PMID- 1461868 TI - Mercury in silastic strain gauge plethysmography for the clinical assessment of the microcirculation. AB - We have used the mercury in silastic strain gauge plethysmography (MSG) system, which is wholly non-invasive, to obtain values (mean +/- s.e.m.) for the following parameters in the legs of supine control subjects: venous pressure (Pv) 9.89 +/- 0.88 mmHg, vascular compliance (Comp) 3.50 +/- 0.29 ml 100 g-1 mmHg-1 x 10(-2), microvascular hydraulic conductivity (Kf) 4.10 +/- 0.16 ml min-1 100 g-1 mmHg-1 x 10(-3) and isovolumetric venous pressure (Pvi) 22.12 +/- 0.82 mmHg. On passive foot-down tilting of control subjects through about 45 degrees, both Pv and Pvi rose to 28.00 +/- 2.33 and 36.58 +/- 2.29 mmHg respectively. The increases in both parameters were highly significant, P < 0.0001. We found that the time course of the vascular compliance component was short if small pressure steps were used. The value increased markedly if large steps were used. We also observed that none of the microvascular parameters studied in the arms differed from those in the legs of the same subjects. We observed that the mean value Kf in the arms of 12 young, non-neuropathic diabetics (9.08 +/- 6.12 x 10(-3)) was significantly greater than that of age and sex-matched controls (P < 0.001). Studies on 14 venous ulceration patients indicated that the values for Kf and Pv were unchanged, whilst those of vascular compliance (5.60 +/- 0.58 x 10(-2) ml 100 g-1 mmHg-1) and Pvi (37.30 +/- 2.25 mmHg) were significantly greater than those found in age-matched controls (P < 0.002 and 0.001, respectively). We feel that Pvi is a useful index of microvascular perfusion. We attribute the pressure dependent difference, in the time course of the vascular compliance response, to the veni-arteriolar reflex. We feel that the pressure dependency of this response might form the basis for the assessment of peripheral autonomic neuropathy. We believe that the MSG system offers a means of monitoring the development of pathologies resulting from microvascular under-perfusion and, of course, the improvement in response to therapeutic interventions. PMID- 1461869 TI - The relationship between cardiac reserve and survival in critically ill patients receiving treatment aimed at achieving supranormal oxygen delivery and consumption. AB - The relationship between survival and cardiac responsiveness to therapy aimed at achieving supranormal values for cardiac index, oxygen delivery and oxygen consumption (cardiac index (CI) > 4.5 l/min/m2, oxygen delivery (DO2) > 600 ml/min/m2, and oxygen consumption (VO2) > 170 ml/min/m2), has been investigated in a heterogeneous group of critically ill patients. Thirty-two patients were prospectively studied and divided into survivors and non-survivors. Cardiac reserve was assessed by determining changes in CI, left ventricular stroke work index (LVSWI) and cardiac power output (CPO) in response to optimal fluid administration and inotropic stimulation with dobutamine. On admission LVSWI and CPO were significantly higher in survivors (P < 0.05), despite no significant differences in pulmonary artery occlusion pressure (PAOP). In response to fluid CI, CPO and LVSWI increased significantly in survivors (P < 0.01), but not in non survivors. Following optimal fluid administration, survivors achieved significantly higher values for CI, LVSWI (P < 0.01), and CPO (P < 0.001) than non-survivors. At maximum resuscitation all three variables were significantly higher in survivors than in non-survivors (P < 0.001). The dose of dobutamine administered to non-survivors (median (range) 100 (5-200)) was significantly greater (P < 0.001) than that given to the survivors (median (range) 10 (0-25)). The dose of dobutamine was limited by complications in 12 of the non-survivors. These observations suggest that cardiac reserve is an important determinant of outcome following critical illness. In unresponsive patients attempts to achieve supranormal oxygen delivery and consumption with massive inotropic support may not only be ineffective but frequently precipitates tachydysrhythmias and myocardial ischaemia. PMID- 1461870 TI - The renal effects of dopamine and dobutamine in stable chronic heart failure. AB - Although an extensive literature exists on factors controlling sodium excretion in animal experimental models of heart failure, the relevance of these to the human condition remains largely unexplored. Increased renal sympathetic stimulation is considered responsible for heightened urinary sodium retention. Stimulation of dopamine receptors is believed to cause a diuresis. Accordingly, we sought to explore the influence of dobutamine (a beta-1 receptor agonist) and dopamine in high and low doses on a frusemide-induced diuresis in patients with chronic stable heart failure. Preliminary results indicate that low doses of dobutamine and dopamine do not increase a moderate, frusemide-induced diuresis. With higher doses dobutamine, but not dopamine, increased urine volume and sodium excretion. These results suggest that direct stimulation of beta-1 receptors increases urinary sodium excretion, either by a direct effect on the kidney or by altering systemic and renal haemodynamics. PMID- 1461871 TI - The health of the nation. PMID- 1461872 TI - An alcohol problem. PMID- 1461873 TI - Malignant melanoma. PMID- 1461874 TI - Assessing family stress. PMID- 1461875 TI - Preventing accidents. PMID- 1461876 TI - Nocturnal enuresis. PMID- 1461877 TI - Chronic childhood disease. PMID- 1461878 TI - Management of HIV infection. PMID- 1461879 TI - A charge of sexual harassment. PMID- 1461880 TI - Oral cancer--diagnosis and management. PMID- 1461881 TI - Coping with tinnitus. PMID- 1461882 TI - Benign breast disease. PMID- 1461883 TI - Work rehabilitation resources. PMID- 1461884 TI - A stimulus to achieve. PMID- 1461885 TI - Access to information. PMID- 1461886 TI - Paternalism or autonomy? PMID- 1461887 TI - Annual reports--who benefits? PMID- 1461888 TI - Improving outpatient visits. PMID- 1461889 TI - Quinolones in general practice. PMID- 1461890 TI - New antibiotics--proceed with caution. PMID- 1461891 TI - [The epidemiological situation and the efficacy of antituberculosis measures in children in West Siberia]. AB - Stabilization of tuberculosis morbidity among the children and adolescents in West Siberia was found against the background of its reduction in adults. The main causes of the unfavourable situation for tuberculosis in children of West Siberia include the presence of numerous infectious foci unknown to the antituberculosis center; incomplete examination of subjects who take care of the newborn; drawbacks in the organization and early detection and vaccination of the newborn and in the follow-up of children of groups IV and VI of dispensary record. PMID- 1461892 TI - [Epidemiology and clinical picture of tuberculosis in children in an ecologically unfavorable coastal zone near the Aral Sea]. AB - Tuberculosis epidemiology was studied in children living in the Ara Sea costal region, in particular in the Karakalpakia, where tuberculosis incidence is twice as high as in the whole region on the average. In conditions of mass dispensarization of the population the rate of tuberculosis detection in children who undergo fluorographic examination from the age of 7 years was 0.06%. In 35% of tuberculosis children the disease took an aggravated course, 68% had intoxication symptoms, 84.6% polylymphadenitis, 23% anemia and 76% presented inhibition of immune reactivity in the form of a decreased number of T lymphocytes and suppression of their functional activity. PMID- 1461893 TI - [Extrapulmonary tuberculosis in children]. AB - Extrapulmonary tuberculosis morbidity in children of the Novosibirsk region for the period of 10 years was analysed on the basis of the materials presented by the regional antituberculosis center. It was found that 44 children has extrapulmonary tuberculosis which accounted for 17.9% of the total number of sick children and 5.7% of all extrapulmonary tuberculosis patients. Tuberculous lymphadenitis was diagnosed in 50% and bone-and-joint tuberculosis in 27.3% of cases; nephrotuberculosis occupied the third and ocular tuberculosis the fourth place; 20% of sick children were detected after their examination and 80% after surgery for other general diseases. Complications of the main process at the moment of application for help had 18.2% of children. The basic causes of later extrapulmonary tuberculosis diagnosis in children is the absence of awareness for tuberculosis in the general practitioners and inadequate work carried out in tuberculosis infection foci. PMID- 1461894 TI - [Outpatient observation and treatment of patients with tuberculosis and massive bacterial excretion aggravated by negative social factors]. AB - Social and epidemiologic features were studied in 1145 newly diagnosed tuberculosis patients in Yakutia who were on the dispensary record in the period between 1981 and 1990. Among the negative social and hygienic factors which aggravated the course of tuberculosis were unsatisfactory living and domestic conditions, failure in family life, unskilled hard labour, idle life, stay in the penitentiary-labour establishments and chronic alcoholism. To improve the effectiveness of dispensary follow-up and treatment of this category of patients measures should be taken aimed at the centralized epidemiologic control. They include, registration of copious bacilli excretors as a special contingent of antituberculosis dispensaries, active measures directed against drug addiction and removal of the unfavourable psychologic factors as well as obligatory hospitalization of patients into specialized tuberculosis centres. PMID- 1461895 TI - [The use of the biochemical and cytochemical indices of the bronchoalveolar lavage fluid for the diagnosis of the activity of pulmonary tuberculosis]. AB - On the basis of guinea pig experiments and clinical findings related to 103 patients of whom 51 were operated on, the authors propose a diagnostic set which allows determination of pulmonary tuberculosis phase. The set informative value is 93.5%. PMID- 1461896 TI - [The potentialities and results of the etiologic diagnosis of acute pneumonias]. AB - The paper deals with the results of the joint Soviet-Hungarian study for the determination of etiology of acute pneumonias. Study included 617 patients. The bacteriologic and serologic methods were used to reveal the causative agent of the disease. Prevalence of Streptococcus pneumoniae (33-49%) in the etiologic structure of acute pneumonias was established both in the USSR and Hungary. In many cases pneumonia is also caused by Haemophilus influenzae (21-22%). In 15-31% of the cases the causative agent of pneumonia is gram-negative microorganisms. A protracted course of acute pneumonia is due to the complex associations of microorganisms including S. pneumoniae. A conclusion has been drawn to the effect that the initial antibacterial therapy should be started with administration of antibiotics that act effectively on S. pneumoniae. PMID- 1461897 TI - [The significance of haptoglobin in the differential diagnosis of tuberculosis of the female genital organs]. AB - Study included 115 women with suspicion of genital tuberculosis. Combined clinical, X-ray and laboratory examination made it possible to classify patients into 3 groups: group 1 included 44 patients with active genital tuberculosis, group 2 32 women with clinically cured tuberculosis of internal genitalia and group 3 39 women with nonspecific genital diseases. The haptoglobin-tuberculin test was given to all patients. High haptoglobin parameters before or 72 h after tuberculin administration were found only in the group of patients with active genital tuberculosis. In groups 2 and 3 the haptoglobin level did not exceed normal values both before and after tuberculin administration in a dose of 50 TU. The informative value of serum haptoglobin parameters in patients with active tuberculosis of internal genitalia constituted 88.6%. PMID- 1461898 TI - [The use of intrapulmonary needle-jet injections of chemical preparations in the preoperative management of patients with pulmonary tuberculosis]. AB - Among the various methods of antibacterial preparation injection for the management of pulmonary tuberculosis the intrapulmonary injection techniques with the help of a needle-stream injector (NSI-1) still remain little studied. The experience of using these techniques for treating more than 200 patients, among whom 23 patients were later operated on, showed that the early use of the method (immediately after the diagnosis was established) helped to stabilize the process in 1-1.5 months. This made it possible to perform operations within 3 months after the diagnosis was made. The method proved effective also in patients who did not present favourable dynamics during 3-6 months of the use of the traditional therapeutic methods. The results obtained allow for the use on a wide scale of needle-stream injections in the preoperative management of destructive tuberculosis patients. PMID- 1461899 TI - [The efficacy of the use of different types of lasers in the operative treatment of patients with tuberculosis of the lungs]. AB - The efficiency of various types of lasers used in the surgical treatment of patients with tuberculosis and other diseases of the lungs and pleura was evaluated. Surgical (CO2 and YAG) and therapeutic lasers (helium-neon, ultra violet and semiconductive) were used. The findings demonstrated that use of various lasers in lung surgery enables one to improve preoperative management, reduce the volume and traumatism of surgical interventions, decrease the number of postoperative complications and increase the effectiveness of surgical treatment of patients with tuberculosis and other diseases of the lungs and pleura. PMID- 1461900 TI - [The combined use of corticosteroids and immunostimulators in the combination therapy of patients with tuberculosis of the lungs (methodologic recommendations]. PMID- 1461901 TI - [The detection of tuberculosis of the lungs using differentiated bacteriologic studies]. PMID- 1461902 TI - [A system of methods of tuberculosis immunodiagnosis based on the use of antigenic preparations isolated from BCG mycobacteria]. AB - The antigenic composition, immunochemical properties and immunogenicity of the antigenic complexes isolated from BCG mycobacteria were studied. A system of sensitive and specific measures of tuberculosis immunodiagnosis has been developed on the basis of specific antigens and antibodies. The informative value of these methods considerably exceeded the previously used test-systems based on the commercial tuberculin. PMID- 1461903 TI - [Lymphocyte enzymes, activity of lipid peroxidation processes and the antioxidant protection of patients with tuberculosis of the lungs]. AB - Activity of succinate dehydrogenase, alpha-glycerophosphate dehydrogenase, NAD2- and NADP2-diaphorases and acid phosphatase in lymphocytes of the peripheral blood as well as malonic dialdehyde and alpha-tocopherol, as parameters of lipid peroxidation defense, were studied in 49 patients with different forms of pulmonary tuberculosis and in 17 practically and clinically healthy subjects. Patients with focal pulmonary tuberculosis presented drop of succinate dehydrogenase and NAD2-diaphorase activity and rise of alpha-glycerophosphate dehydrogenase and NADP2-diaphorase activity in lymphocytes. Parameters of malonic dialdehyde and alpha-tocopherol in patients and healthy subjects had no difference. Patients with infiltrative and fibrocavernous pulmonary tuberculosis had drastic suppression of energy enzymes and sharp rise of acid phosphatase activity in lymphocytes, which correlated with a significant rise of malonic dialdehyde level and decrease of blood serum alpha-tocopherol. There was a tendency to an increase in energy enzymes activity and decrease of acid phosphatase activity 3-4 months after chemotherapy, which was followed by the clinical improvement of patients' condition. Direct dependence was found between the normalization of enzyme activity of lymphocytes and diminution of lipid peroxidation processes. PMID- 1461904 TI - [Results of carrying out a planned program "Acceleration of the tempo of lowering the tuberculosis morbidity in the RSFSR, 1983-1990"]. AB - Analysis of the results of a planned program "Acceleration of the tempo of tuberculosis morbidity reduction in the RSFSR for the period of 1983-1999" has shown that formally it was fulfilled in 60 of the 73 administrative territories. The tempo of morbidity reduction during 1986-1990 was 24.2% in relation to 1985. This high tempo was associated with reduction of the volume of prophylactic screening examinations from 75% in 1985 to 52% in 1990. Hence, acceleration of the tempo of tuberculosis morbidity reduction is not genuine. Changes in socioeconomic conditions in the region should be taken into consideration in compiling planned programs. The basic aim of the program is to preserve a positive dynamics of the main epidemiologic indices for tuberculosis by finding the optimal model for the transition of the phthisiatric service to a new mechanism of economy. PMID- 1461905 TI - [Pneumotropic microorganisms in chronic diseases of the respiratory organs and tuberculosis of the lungs]. AB - Species composition and the etiologic role of S. pneumoniae and of bacteria of Haemophilus genus in origination and maintenance of diverse lung pathology were specified and the problem of their carriage in pulmonary tuberculosis patients in the absence of nonspecific infection was investigated. The results of study have confirmed that S. pneumoniae was and still remains one of the most common pathogens of chronic respiratory diseases (55.8% of bacteria was found in sputum and 64.7% in bronchoalveolar lavage and exudate). Serological verification of microorganisms isolated from the sputum by the indirect immunofluorescence method was obtained in 77.4% of the studies. Bacteria of Haemophilus genus were more often isolated together with pneumococcus (15.4%) and were verified serologically in only 31.8% of the cases. Transitory (asymptomatic) carriage was found in 412 pulmonary tuberculosis patients. S. pneumoniae accounted for 62% and Haemophilus for 20%. PMID- 1461907 TI - [The dynamics of the cessation of bacterial excretion and the closing of solitary destruction cavities in relation to their dimensions in tuberculosis of the lungs]. PMID- 1461906 TI - [Serological studies of synanthropic birds for infection by M. avium]. AB - Examination for M. avium contamination covered 702 specimens of the synanthropic birds of 6 species (hooded crows, daws, rooks, magpies, sparrows, starlings) which was carried out in 13 landscape-epizootic areas of the northern zone of the Low Volga region. Contamination was studied by a serological test (AIT) using the M. avium extract and dry avian tuberculin as an antigen in the parallel tests. It was found that 96 (23%) of the 416 specimens from the right bank of the Volga and 65 (22.72%) of the 286 birds from the left bank were AIT-seropositive. The paper presents methods of study and contamination parameters of birds; the character of distribution of the infected birds by the region of the examination zone is discussed. PMID- 1461908 TI - [The application of a reversion of the lower lobe of the lung in the practice of a thoracic department]. PMID- 1461909 TI - [The effect of low-intensity laser irradiation on the peroxide-oxidant system of the blood in patients with infiltrating tuberculosis of the lungs]. PMID- 1461910 TI - [A mesenteric cyst masquerading as tuberculosis in a 10-year-old girl]. PMID- 1461911 TI - [Analysis of the causes of mortality in the immediate and long-term periods of follow-up of patients who underwent pulmonectomy for disseminates forms of tuberculosis of the lungs]. PMID- 1461912 TI - [Tuberculosis of the bronchi: problems of pathogenesis and interrelations with different clinical roentgenologic forms of tuberculosis of the respiratory organs]. PMID- 1461913 TI - [BCG vaccination and its significance in present conditions (review of the foreign literature 1980-1990)]. PMID- 1461914 TI - [Tuberculosis in the Ural and Volgo-Vyatka regions and means for optimizing antituberculosis activity]. AB - Analysis of certain parameters has demonstrated that situation for tuberculosis in the Ural and Volgo-Vyatsky region for the period of 1986-1990 remains unsteady. The epidemiologic and economic conditions of today dictate the necessity to improve the effectiveness of tuberculosis control by strictly differentiating the available antituberculosis measures, their volume and frequency of use, depending on the risk of disease contraction in each particular territory in the whole population and in separate groups taking technical, material and personnel potentialities into consideration. PMID- 1461915 TI - [Tuberculosis morbidity among the population of a large industrial center]. AB - Tuberculosis morbidity in children, adolescents, young people and adults for the period of 1986-1990 has been analysed. Parameters of morbidity were compared with general morbidity of the population of Chelyabinsk. It was found that at the present stage of tuberculosis control parameters of general morbidity remained unchanged. Morbidity in adolescents and young people aged 18-19 years markedly decreased, while a tendency to its slow growth was revealed in children and in subjects aged 24-29 years. In contrast to other groups, parameters of morbidity in adults are the highest (32.7-37.4 per 1,000,000) and steady owing to which measures aimed at tuberculosis control should be improved. PMID- 1461916 TI - Autoxidation and yellowing of methyl linolenate. AB - The autoxidation of fatty esters of linseed oil is studied extensively, and the products formed from these reactions are identified. The mechanism suggested for autoxidation, helps to understand fat deterioration resulting in offensive odours and flavours, and to develop new antioxidants to prevent this decomposition. The oxidation following oxidative copolymerization should be investigated in order to understand and to develop new methodology to prevent yellowing. Although the yellowing of indoor oil paints could be prevented to an extent, no compound is known to completely inhibit this process nor has the cause for this yellow colouration been isolated, leaving the doors wide open for further investigation. PMID- 1461918 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1461917 TI - Role of oxidized low density lipoprotein in atherogenesis. PMID- 1461919 TI - Cigarette smoking reduces human salivary eicosanoids. AB - The effect of cigarette smoking on salivary eicosanoid levels was investigated in 10 smoker and 10 non-smoker volunteers. The smokers consumed an average of 20 cigarettes/day for the past 5 years or longer. The smoking status was validated by salivary cotinine level. Eicosanoids were extracted from saliva with ethanol, and the radioimmunoassay was performed to determine the concentrations of four major eicosanoids, i.e. prostaglandin E2 (PGE2), PGF2 alpha, 6-sulphidopeptide containing leukotrienes (LTs) and 12-hydroxyeicosatetraenoic acid (12-HETE). The levels of PGE2, PGF2 alpha, and LTs were significantly lower in the saliva of smokers as compared to that of the non-smokers (1.74 +/- 0.32 vs 2.41 +/- 0.64, p = 0.006; 0.36 +/- 0.12 vs 0.54 +/- 0.18, p = 0.04; 2.24 +/- 0.96 vs 4.92 +/- 1.29, p = 0.006; mean +/- SD, ng/ml saliva). No significant differences were found in the levels of 12-HETE between the two groups. The results suggest that cigarette smoking reduces the concentrations of both the cyclooxygenase and 5 lipoxygenase products in saliva. PMID- 1461920 TI - Brain tissue injury and blood-brain barrier opening induced by injection of LGE2 or PGE2. AB - The hypothesis that the accumulation of prostaglandin (PG)E2 during reperfusion of severely ischemic tissue contributes to a breakdown in the blood-brain barrier (BBB) was expanded to include a parallel role for levuglandins(LGs), gamma ketoaldehydes produced by rearrangement of PGH2. LGE2 was shown to be more potent than PGE2 in causing breakdown of the BBB when injected intrahemispherically. Brain tissue necrosis was clearly evident with total doses of levuglandin as low as 100 nmole. PMID- 1461921 TI - Amniotic fluid embolism and leukotrienes--the role of amniotic fluid surfactant in leukotriene production. AB - Surfactant rich lipid (lipid) was extracted from cell free 10,000 x g pellets of amniotic fluid. White blood cells (WBC) were isolated from human donors. 36 x 10(7) WBC and 5 g rabbit lung were incubated with pretreated lipid or dipalmitoyl lecithin (lecithin). Leukotrienes (LTs) were identified by high performance liquid chromatography (HPLC) and bioassay, and quantified by radioimmunoassay. Peaks of LTC4 and LTD4 on HPLC and guinea-pig ileum contraction could be identified in lipid and lecithin groups, but not in the control group. LTC4 production by lipid and lecithin groups was significantly higher than that by the control group. An involvement of amniotic fluid surfactant in leukotriene production is suggested. PMID- 1461922 TI - Alteration of platelet activating factor (PAF) metabolism in rat pulmonary alveolar macrophages and plasma by cigarette smoking. AB - The pathophysiological role of platelet activating factor (PAF) in smoking induced disorders was examined in rats exposed daily to smoke for 10, 18 and 26 weeks. The concentration of PAF in bronchoalveolar lavage fluid and the activities of PAF biosynthetic and catabolic enzymes in alveolar macrophages and in plasma were determined. The concentration of PAF in lavage fluid of the smoke exposed group was significantly lower than that in the sham group for each duration of smoke exposure. The PAF biosynthetic enzyme, acetyl transferase, activity in alveolar macrophages of smoked group was less than that in the sham group although the difference was not statistically significant. PAF catabolic enzyme, acetyl hydrolase, activities in alveolar macrophages and in plasma were all significantly higher in every smoked group than in the sham group. These data indicate that cigarette smoking alters PAF metabolism in the respiratory tract and in plasma and such an alteration may contribute, at least in part, to smoking induced cardiopulmonary disorders. PMID- 1461923 TI - The influence of fish oil supplementation on plasma lipoproteins and arterial lipids in vervet monkeys with established atherosclerosis. AB - There is controversy about whether supplementing diets with marine fish oil can regress, promote or prevent atherosclerosis. Therefore the effects of an Atlantic pilchard oil (FO) supplement and dietary change were measured in a proven atherosclerosis model. Vervet or African Green monkeys were fed an atherogenic diet (AD) for long enough to ensure progression before treatments started. Matched groups were then treated for 20 months, either by adding FO to the AD (AD/FO), or by changing to a therapeutic diet with FO (TD/FO). Control treatments consisted of supplementing with sunflower oil (SO) instead of FO, so that treatments were AD/SO and TD/SO. The same total polyunsaturates were supplied by the FO and SO and the dose of FO was realistic (2.5% of total energy). A reference group (R) received the TD with no oil supplements. Supplementing with FO did not change the concentrations of total, low or high density lipoprotein cholesterol in plasma. After The AD/FO the intimas of aortas contained more total (p < or = 0.001), free (p < or = 0.05) and esterified (p < or = 0.05) cholesterol, total phospholipid (p < or = 0.01) and sphingomyelin (p < or = 0.05) than after the AD/SO. After FO supplementation eicosapentaenoic acid was significantly higher and arachidonic acid significantly lower in the plasma and aorta intima phosphatidylcholine. None of these changes was anti-atherogenic in terms of atherosclerosis measured in the same individuals (1). Nor did FO increase the efficacy of the TD. PMID- 1461924 TI - On the role of 'in vivo' injected progesterone and of the 'in vitro' presence of oxytocin, modulating Ca2+ uptake by the rat uteri from spayed animals and as controllers of the production of arachidonic acid metabolism. AB - We attempted to explore possible mechanism(s) subserving the influence of oxytocin (O) and of progesterone (P) in the isolated rat uterus studying the action of these hormones on: the synthesis and release of prostaglandins (PGs), the metabolism of labelled arachidonic acid and the uptake of Ca2+ by the tissue from ovariectomized animals. The experiments were done with uterine preparations isolated from spayed rats treated or not with P prior to sacrifice and afterward incubated or not with O 'in vitro'. While uterine strips from untreated spayed rat uterus exhibited a basal release into the incubating medium of approximately the same amounts of PGF2 alpha, and PGE2, the 'in vitro' addition of O (50 mU/ml) increased significantly (p < 0.05) the output of PGF2 alpha without changing the release of PGE2. In tissue from rats injected with P prior to sacrifice the output of PGF2 alpha rose significantly (p < 0.01) as it did after the addition of O to preparations obtained from spayed rats treated with P in comparison to findings in uteri from spayed rats but not in comparison to uteri from spayed rats treated with P alone. Moreover, the 'in vitro' addition of O (50 mU/ml) only increased the formation of PGF2 alpha (p < 0.05) and of 5-HETE (p < 0.05); nevertheless the administration of P to spayed rats diminished significantly (p < 0.05) the formation of 6-keto-PGF1 alpha from uteri, but increased that of PGF2 alpha (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1461925 TI - Sex and dietary fat modulate hepatic prostaglandin F2 alpha in F344/N rats. AB - The study was designed to determine whether sex and fat calories altered hepatic prostaglandin (PG) F2 alpha status; a factor which may reflect susceptibility to cancer development. For 4 weeks, groups of 8 male and 8 female F344/N rats were fed diets with 9% of energy (en%) from linoleate and 15.5, 20, 30 or 40 en% fat. Females had greater hepatic stearate, arachidonate and PGF2 alpha whereas males had greater hepatic myristate, palmitate and oleate. Females also had greater plasma stearate levels. Greater hepatic arachidonate may have stimulated PG production in females. Hepatic oleate increased and hepatic palmitate decreased with increasing en% fat (p < 0.05). Hepatic stearate was greater and hepatic linoleate less when 40 en% fat was fed compared with other levels of dietary fat (p < 0.05). Plasma oleate was greater at 30 or 40 en% fat than at lower levels of fat, whereas plasma linoleate was less at 40 en% than at 15.5% en% fat. The ability of a 30 en% fat diet, containing equal proportions of linoleate and oleate, to suppress hepatic PG production may be related to the effects of dietary fat content and composition on plasma fatty acid profiles. Because suppressed PG production has been linked with suppression of cancer development, dietary recommendations to consume 30 en% fat with a P:M ratio of 1:1 may be cancer-protective. PMID- 1461926 TI - Does a HDL injection reduce the development of serum hyperlipidemia and progression of fatty streaks in cholesterol fed rabbits? AB - The influences of homologous (rabbit) or heterologous (human) high density lipoprotein (HDL) on the development of serum hyperlipidemia and progression of fatty streaks were studied in cholesterol fed rabbits. Three groups of New Zealand rabbits were fed a 0.5% cholesterol rich diet for 8 weeks. Additionally into these animals the following solutions were injected intravenously two times per week: group 1 (control): saline; group 2: human HDL dissolved in saline; group 3: rabbit HDL dissolved in saline. The animals of group 2 had lower serum cholesterol levels during the dietary period than rabbits of group 1 (p < 0.05) but the surface of intima covered with fatty streaks was the same as in group 1. On the other hand, the serum cholesterol level in rabbits of group 3 was the same as in group 1 during the whole experimental period, but the surface of aorta covered with fatty streaks was significantly lower (p < 0.05) in group 3 than in group 1. The results of this study support the hypothesis of an antiatherogenic action of HDL, which seems to be independent of the influence of HDL on the serum lipids but depends on the source of HDL. PMID- 1461927 TI - Binding of a thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist to rabbit and pig heart membrane protein. AB - This study aimed at testing the hypothesis that the binding sites for TXA2/PGH2 are present and different in the heart as compared to platelets and blood vessels. Kinetic studies on the thromboxane binding to protein of membrane preparations from rabbit and pig hearts were carried out using [125I]-PTA-OH, a potent specific thromboxane receptor antagonist. The following points are stressed: 1. the binding sites to 125I-PTA-OH were shown to be present in the heart membrane whatever the adopted experimental conditions were i.e. the temperature (4 or 30 degrees C) used for incubation the protein fractions under study: either the 105,000 g supernatant or the 200,000 g supernatant of the solubilized pellet (105,000 g) the animal species: rabbit and pig 2. the radioligand binding was rapid, saturable and reversible 3. the kinetically determined Kd's were in the picomolar range--11 and 14 pM for the rabbit and pig heart membrane preparation respectively--instead of the nanomolar range found in other tissues of the nanomolar range found in other tissues--27-39 nM and 2 nM for human platelets and bovine artery endothelial cells respectively- using the same thromboxane receptor antagonist. PMID- 1461928 TI - NZB/NZW F1 mouse nephritis and immune response are not changed by treatment with a 15-lipoxygenase derivative. AB - 15-HETE is an arachidonic acid derivative issued from the 15 lipoxygenase pathway. This fatty acid possesses immunomodulatory capabilities since it was reported that it generates CD8 + suppressor T-cells either in vitro or ex vivo. The aim of the present report was to study if the suppressive capabilities of 15 HETE were able to influence the onset of the NZB/NZW Fl auto-immune disease. For that purpose we produced 15-HETE and injected the eicosanoid twice a week to NZB/WFI mice for 40 weeks. During the 15-HETE treatment of the animals it was observed an augmentation of the proliferative response of lectin-stimulated splenocytes (at weeks 20 and 30) then the thymidine uptake decreased (at week 40). In fact we observed that among 15-HETE treated mice the evolution of the nephropathy was not changed, the 'glomerular activity score' remained the same for the treated animals compared to controls. On the contrary antinuclear antibodies occurred earlier even if in some experiments the generation of CD8 + cells was demonstrated. PMID- 1461929 TI - Quantitative association between altered plasma esterified omega-6 fatty acid proportions and psychological stress. AB - Medical students (MS) tested during the first year of medical school showed both greater stress on the Brief Symptom Inventory and lower plasma proportions of total esterified arachidonic acid (AA, C20:4n-6), and its omega-6 fatty acid (FA) precursor, linoleic acid (C18:2n-6) than control laboratory workers. This association suggests that omega-6 FA metabolism may be affected during stress. Low AA values might result from depletion of plasma stores for immunoregulatory prostenoids formation or from modification of metabolic pathways by cortisol or other cytokine compounds implicated in stress. Values for other major FA and the omega-3 neuronal metabolic substrate, docosahexaenoic acid (DHA, C22:6n-3) were similar between students and controls. The clear preservation of the omega-3 FA pathway suggests their programmed availability for neuronal function during stress. Since plasma FA proportions may affect immune cell membrane function(s), we suggest that altered values of plasma FAs may be an important component of the physiological effects of psychological stress. PMID- 1461930 TI - Modulation of prostacyclin production by cytokines in vascular endothelial cells. AB - The data presented in this review clearly show that many different cytokines regulate the synthesis of PGI2 in vascular EC (Tables 1 & 2). Since these agents are synthesized, stored, and/or released from platelets, leukocytes and cells present in the vascular wall (Fig.), they are to be found at sites of vascular injury and may, through their effect on the synthesis of PGI2 and other prostanoids, regulate thrombogenesis and atherogenesis. Despite the mass of detailed data, the picture is still fragmentary. Very little, for instance, is known about the 'orchestral effects' of different combinations of cytokines. In addition, it seems that the regulation of PGI2 synthesis by cytokines varies with the species and with the type of vasculature from which the cells originated. However, discrepancies may also be due to the use of different culture conditions. Moreover, we must remember that the present data are almost exclusively from in vitro studies, and the representativeness of these results in in vivo situations remains to be clarified. PMID- 1461931 TI - Cancer destruction in vivo through disrupted energy metabolism. Part I. The endogenous mechanism of self-destruction within the malignant cell, and the roles of endotoxin, certain hormones and drugs, and active oxygen in causing cellular injury and death. AB - Autoxidative cellular injury arises when an intact endogenous mechanism present in cells is triggered by a range of specific stimuli, including endotoxin, stress hormones, hydralazine, L-isoproterenol and certain phenothiazines. The overall changes involve oxygen activation, lipid peroxidation, and the generation of substances which disrupt mitochondrial energy production by uncoupling oxidative phosphorylation. Magnetic resonance spectroscopy has revealed that falls in high energy phosphate are commonly seen following a variety of therapeutic procedures, including radiation and treatment with cytotoxic agents. Sometimes the energy status of a tumor improves in response to therapy; in these instances tumor regression is due to programmed cell death, termed apoptosis. In the first part of this review the roles played in the development of autoxidative cellular injury by oxygen and its active forms, an endogenous peroxidisable substrate, and an oxygenase are considered and discussed. PMID- 1461932 TI - Cancer destruction in vivo through disrupted energy metabolism. Part II. Lipid peroxidation and cell death; drug resistance as a consequence of reversible cellular injury. AB - In the second part of this review of autoxidative cellular injury and death in tumor cells, the presence of saturated or polyunsaturated fatty acids, vitamin E, and free or esterified cholesterol in whole cells and organelles is discussed in the context of enhancing or attenuating lipid peroxidation. The disposition of unsaturation within polyunsaturated fatty acid molecules is critical for tumor promotion, but the situation appears ambivalent with regard to inflicting cellular injury. Increases in lipid peroxidation and phospholipase A2 activity following on from the administration of hormones or non-cytotoxic drugs are considered from the viewpoint of generating hydroperoxyfatty acids and lysophosphatides, both of which disrupt mitochondrial energy production by uncoupling oxidative phosphorylation. The metabolic fate of lysophosphatides is thought to be a crucial factor both in determining whether cancer cells survive or not, and in furnishing protection for surviving cells against subsequent attack. Both energy-dependent and energy-independent mechanisms for acylating lysophosphatides are reviewed. The emergence of an unstable form of drug resistance during the recovery phase is interpreted in terms of the chemical identity of the new acyl groups on the acylated lysophospholipid. Resistance to further free radical challenge can be conferred by the regeneration of phospholipids bearing saturated or monoenoic 2-substituents which are unable to undergo peroxidation. PMID- 1461933 TI - Cancer destruction in vivo through disrupted energy metabolism. Part III. Spontaneous drug resistance, selectivity of antineoplastic action, and strategies for intensifying tumor injury. AB - In the concluding section of this review of cancer destruction by disruption of energy metabolism, the cellular mechanism for interfering with energy production is considered in terms of drug resistance arising independently of previous tumor injury. The occurrence of various degrees of damage to cancerous growths as a consequence of secondary shock is interpreted on the basis of elevated levels of stress hormones, including vasopressin, which have earlier been shown to interfere with energy metabolism in a murine sarcoma. Similarly, the indirect action of various antineoplastic procedures can be related to a role for the endocrine system, with particular reference to vasopressin and inappropriate anti diuretic hormone secretion syndrome. Multiple drug resistance is also discussed, and the mode of action of the topoisomerase inhibitor doxorubicin is critically examined. The basis of selectivity of disruption of energy metabolism by substances such as hydralazine and L-isoproterenol is discussed from the viewpoint of altered activities of antioxidant enzymes in transformed cells, but these considerations alone are not thought to be sufficient to account for the highly specific nature of the antineoplastic action. Conversely, antioxidant enzymes, more especially those concerned with glutathione metabolism, probably play a major role in multiple drug resistance, although in this respect the case of autoxidative cellular injury awaits attention. Theoretical strategies for the intensification of tumor injury include the aim of prolonging the half-lives of lysophosphatides within damaged tissue. Whereas the clinical application of the principle of tumor destruction through selective disruption of energy metabolism is at present compromised for lack of information, the use of phenothiazines as antineoplastic agents is feasible, and awaits serious exploitation. The relative lack of incapacitating side-effects of phenothiazines should provide an attractive change for the clinical oncologist. PMID- 1461934 TI - Investigation of the possibility of solitary waves in the base stacks of DNA. AB - The possibility of the existence of solitary waves in DNA is investigated. On the basis of our classical model we do not find such a wave in a polynucleotide, but for a stack of adenine molecules without backbone we observe one. Possible extensions of the model for DNA are discussed. From our results we can conclude, that solitons exist in stacked systems without an additional backbone. At least the degree of freedom which couples a nucleotide base (pair) to the sugar phosphate backbones (N-C stretching vibration) has to be treated with the help of the quantum equations of motion. PMID- 1461935 TI - Molecular effects of nitrosamine toxicity. AB - Nitrosamines are toxic chemical compounds found low in quantity, but widespread in the environment. This work investigated the kinetics of chemical reaction of activated nitrosamines with various organic substrates. The mechanism by which nitrosamines react demonstrates possible pathways in which the toxicity is expressed. Once activated nitrosamines are very reactive. Chemical compounds which can act as nucleophilic substrates may be alkylated by the activated nitrosamines. A broad category of chemical compounds are shown to be suitable substrates for nitrosamine induced alkylation. This large category of substrates suggests a substantial potential for toxic activity in vivo. By investigating the reaction kinetics of activated nitrosamines a greater understanding of their toxic effects may be possible. PMID- 1461936 TI - Use of animals in medical education. PMID- 1461937 TI - The large plasmids found in enterohemorrhagic and enteropathogenic Escherichia coli constitute a related series of transfer-defective Inc F-IIA replicons. AB - Forty-six of 52 (88.5%) enterohemorrhagic Escherichia coli (EHEC) strains screened carried a "common" plasmid of about 90 kb which encoded sequences homologous to the Inc F-IIA replicon. A similarly high incidence of Inc F-IIA plasmid-containing strains was observed in other groups of diarrheagenic E. coli, but not in random environmental coliform isolates. Enteropathogenic E. coli (EPEC) contain plasmids of similar properties and share a 23-kb DNA fragment with plasmids from EHEC. The common region encodes the F-IIA replication region and sequences homologous to the transfer operon of the Inc F-II plasmid R1. Sequence homology varied between plasmids isolated from different EHEC/EPEC strains with > 80% showing homology to the regions encoding the rep and par genes. Only 5% of plasmids from EHEC strains had intact sequences homologous to the DNA between these two regions, including the oriT site. Some plasmids with an apparently intact tra operon still failed to plaque F-pilus-specific phages. This is consistent with observations that the large plasmids of EHEC and EPEC are phenotypically nonconjugative. These results suggest that the large plasmids of EHEC/EPEC constitute a family of transfer-deficient Inc F-IIA plasmids with varying degrees of deletion in tra function. The evolutionary ramifications of this finding are considered. PMID- 1461938 TI - Transformation of Acetobacter xylinum with plasmid DNA by electroporation. AB - Genetic analysis of Acetobacter xylinum, a cellulose-synthesizing bacterium, has been limited by lack of a successful transformation method. Transformation of A. xylinum was attempted using two broad-host-range plasmids (pUCD2 and pRK248) and a variety of transformation methods. Methods using CaCl2, freeze/thaw treatments, and polyethylene glycol were unsuccessful. Transformation of a cellulose-negative strain of A. xylinum with plasmid DNA has been achieved with high-voltage electroporation. Electroporation conditions of 25 microF capacitance, 2.5 kV, 400 ohms resistance, and pulse lengths of 6-8 ms were applied to a cell/DNA mixture in a 0.2-cm cuvette. Plasmid pUCD2 transformed at an efficiency of 10(6)-10(7) transformants/micrograms DNA and pRK248 yielded 10(5) transformants/micrograms DNA. The frequency of transformation increased linearly with increasing DNA concentration, while transformation efficiency remained constant. pUCD2 was recovered from transformants following chloramphenicol amplification and observed by agarose gel electrophoresis. Both plasmids could be reisolated from Escherichia coli after back-transformation with alkaline lysis DNA preparations from Acetobacter transformants. Electro-transformation of A. xylinum with plasmid DNA suggests its potential use for analysis of the A. xylinum genome. PMID- 1461939 TI - Deletion derivatives of pAgK84 and their use in the analysis of Agrobacterium plasmid functions. AB - The 47.7-kb plasmid pAgK84, present in Agrobacterium radiobacter strain K84, confers production of a novel, highly specific, antiagrobacterial antibiotic called agrocin 84. Strain K84 is used commercially to biocontrol crown gall caused by agrocin 84-susceptible strains of Agrobacterium tumefaciens. Efficient biocontrol is dependent upon production of agrocin 84 by strain K84. Starting with a derivative of pAgK84 containing a Tn5 insertion, a series of deletion derivatives of the plasmid were isolated. The smallest of these, pJS500, contains about 8 kb of the original agrocin plasmid and localized the replication functions to between 4 and 6 o'clock on the physical map. A smaller derivative, produced by clonal rescue of a Tn5 insertion in the 4 o'clock region, further localized the minimal replication functions to a 1.5-kb region mapping between coordinates 18.1 and 19.6. Analysis of plasmid stability indicated that functions required for maintenance of the plasmid under nonselective conditions are tightly linked to the minimal replication region. This region also encodes incompatibility functions; the deletion derivatives were all incompatible with the wild-type pAgK84. The stability/replication locus of pAgK84 maps just anticlockwise from the Tra region. This region is retained fully in pAgK1026, the directed Tra- derivative of pAgK84 which is now in use as the primary crown gall biocontrol agent in Australia. One of the deletion derivatives, the 15-kb pJS400, was used as a vector to clone the KpnI fragments of an octopine-type Ti plasmid. Traits known to be encoded on these fragments were expressed and properly regulated in Agrobacterium hosts. One clone, encoding the Ti plasmid replication/incompatibility region, was used to cure IncRh1 Ti plasmids from their hosts. This clone also was found to be incompatible with pAtK84b, a large plasmid encoding opine catabolism present in A. radiobacter strain K84. This indicates that the opine catabolic plasmid is closely related to the IncRh1 Ti plasmids. PMID- 1461940 TI - Promoter probe and shuttle plasmids for Deinococcus radiodurans. AB - Two improved Deinococcus radiodurans-Escherichia coli shuttle vectors have been constructed. pI3 is a 16-kb plasmid that confers chloramphenicol resistance in D. radiodurans (CmR, cat) and ampicillin resistance in E. coli (ApR) and contains a multiple cloning site that does not interrupt sequences necessary for replication or drug resistance in either host. pI304 is a promoter-probe plasmid that is similar to pI3, but lacks the D. radiodurans promoting sequence for the cat gene, while retaining sequences necessary for replication. PMID- 1461941 TI - Construction of recA mutants of Acholeplasma laidlawii by insertional inactivation with a homologous DNA fragment. AB - Mycoplasmas (class Mollicutes) are wall-less prokaryotes phylogenetically related to gram-positive bacteria. This study describes the construction of recA mutants of the mycoplasma Acholeplasma laidlawii. An internal fragment of the recA gene from A. laidlawii was cloned into a plasmid that does not replicate in this organism. When this plasmid construct was used to transform A. laidlawii, it inserted into the chromosome, disrupting the recA gene. The phenotype of the resulting recA mutant was compared to that of wild-type cells and to that of a strain that has a naturally occurring ochre mutation in its recA gene. As found in other bacterial systems, loss of RecA activity resulted in cells deficient in DNA repair. PMID- 1461942 TI - Nucleotide sequence of the chloramphenicol resistance determinant of the streptococcal plasmid pIP501. AB - We have sequenced the chloramphenicol resistance determinant (cat) of plasmid pIP501 from Streptococcus agalactiae to investigate its relationship with other cognate cat determinants. Sequence analysis revealed that it exhibits a high degree of similarity with the cat genes of plasmids pC221 and pUB112 from Staphylococcus aureus and pSCS1 from Staphylococcus intermedius. These genes, however, display several differences in their regulatory and coding regions. These results demonstrate that the cat determinant of plasmid pIP501 belongs to the pC221 subgroup of CAT variants. PMID- 1461943 TI - Monoamine oxidase and cortisol response in depression and schizophrenia. AB - The relationship between hypothalamic-pituitary-adrenal (HPA) axis function and platelet monoamine oxidase (MAO) activity was examined in drug-free depressed (n = 32) and schizophrenic (n = 36) inpatients. HPA function was measured by determining plasma cortisol levels at 8:30 a.m. and 11 p.m. before, and 8:30 a.m., 4 p.m., and 11 p.m. after administration of 1 mg of dexamethasone (DEX). There was a significant correlation between platelet MAO activity and all post DEX cortisol levels (8:30 a.m., 4 a.m., and 11 p.m.) in depressed patients, and MAO activity and pre-DEX cortisol levels (11 p.m.) in schizophrenic patients. MAO activity was significantly higher in depressed DST nonsuppressors than in suppressors, and there were more DST nonsuppressors in high-MAO groups as compared with low-MAO groups. Our results thus suggest a strong relationship between platelet MAO activity and HPA function in depressed patients. These biochemical markers are potentially useful in the identification of biochemically and clinically homogeneous subgroups of depressed patients. PMID- 1461944 TI - Auditory sensory gating and catecholamine metabolism in schizophrenic and normal subjects. AB - Diminished neuronal response to repeated sensory input is a sensory-gating phenomenon that has been found to be deficient in schizophrenic patients. For example, schizophrenic patients fail to decrease the amplitude of the P50 wave of the auditory evoked potential to the second of paired click stimuli. In some studies, however, normal subjects have also failed to decrease their P50 responses. The aim of this study was to determine if accommodation to the recording situation over time would affect the gating of the P50 response. The gating of the P50 wave is measured as the ratio of the amplitude of the second response to the amplitude of the first. Three successive auditory evoked potentials were compiled, each from trains of 32 pairs of stimuli. Twelve normal subjects and 12 schizophrenic patients were studied. Unconjugated catecholamine metabolites were measured from venous samples drawn before and after the electrophysiological recording. Between the first and third trials, the normal subjects significantly increased their gating of P50. This increase in gating of P50 was related to decreased levels of the noradrenergic metabolite 3-methoxy-4 hydroxyphenylglycol. No similar phenomenon was observed in the schizophrenic patients, a number of whom had a further decrease in P50 gating over the three trials. Transient failure to observe gating of P50 in normal subjects may be related to increased state-dependent noradrenergic activity, which is known to disrupt sensory gating. This mechanism does not seem to account for the more persistent failure of sensory gating in schizophrenia. PMID- 1461945 TI - Secondary social phobia in patients with major depression. AB - Nineteen of 42 (45.2%) patients were socially phobic when and only when depressed. Each of these patients met diagnostic criteria for primary depression (Research Diagnostic Criteria) and major depression (DSM-III-R). Every subject had three or more distinct episodes of depression. Eight of the 9 men (88.9%) and 11 of the 33 women (33.3%) were socially phobic when depressed (p = 0.004). Patients with recurrent wintertime episodes of major depression (p = 0.036) and a past history of alcohol or drug abuse were more likely to be socially phobic (p = 0.0001). The authors suggest the 19 socially phobic patients with primary depression should be regarded as having secondary social phobia. Secondary social phobia may be an important source of comorbidity in patients with primary depression. PMID- 1461946 TI - Panic disorder and major depression: a comparative electroencephalographic sleep study. AB - Family studies suggest some common etiological factors in panic disorder and depression. The observation of characteristic depression-like polysomnographic alterations in panic disorder patients would further underline the assumed biological interface between the two psychiatric disorders. In a polysomnographic study of 22 inpatients with panic disorder, 12 inpatients with major depression, and 12 control subjects, we found that both groups of patients had one major feature of depression-like sleep: a shortened rapid eye movement (REM) latency. However, the patterns of the first hours of polysomnography showed more differences than similarities between these psychiatric disorders, indicating that the shortened REM latency apparently is merely a common final pathway of different alterations in sleep regulation. Our findings, therefore, provide more evidence against than for a significant biological interface between panic disorder and depression. PMID- 1461947 TI - Relationship between symptoms rated with the Positive and Negative Syndrome Scale and brain measures in schizophrenia. AB - The Positive and Negative Syndrome Scale (PANSS) was used to rate clinical symptoms in 42 inpatients with schizophrenia before they were examined by computed tomography. Significantly higher mean size of lateral and third ventricles, and higher mean cortical atrophy were found in schizophrenic patients compared with healthy control subjects. Ventricular enlargement and cortical atrophy were significantly related to low scores on the Composite subscale of the PANSS. Positive correlations were observed mainly with negative items such as blunted affect, emotional withdrawal, difficulties in abstract thinking, passive apathetic social withdrawal, and lack of spontaneity of conversation. Additional positive correlations were observed with two items from the General Psychopathology subscale (mannerisms and disorientation). Inverse correlations were found with most positive items. These results suggest a relationship between brain structural abnormalities and the symptomatology of schizophrenia recorded with PANSS. PMID- 1461948 TI - In vivo assessment of pituitary volume with magnetic resonance imaging and systematic stereology: relationship to dexamethasone suppression test results in patients. AB - The relationship between dexamethasone suppression test (DST) results and in vivo pituitary volume was studied in 24 psychiatric inpatients. The principles of systematic stereology were used to measure pituitary volume from 3-mm contiguous sagittal spin-echo magnetic resonance (MR) images of the brain. There was no correlation between pituitary volume and 3 p.m. or 10 p.m. postdexamethasone (post-DEX) plasma cortisol concentrations. However, when multiple regression analysis was performed to relate pituitary volume to gender, age, and post-DEX plasma cortisol concentrations, there was a significant relationship between pituitary volume and age, gender, and 10 p.m. post-DEX cortisol plasma concentration. This is the first study to demonstrate a method that directly measures, rather than estimates, in vivo pituitary volume. Furthermore, it suggests that activation of the hypothalamic-pituitary-adrenal axis in psychiatric patients, as manifested by elevated post-DEX cortisol concentrations, may influence pituitary volume. PMID- 1461949 TI - Lithium determination in outpatient clinics by an ion-selective electrode in venous and capillary whole blood. AB - The use of an ion-selective electrode (ISE) to determine lithium (Li) in routine clinical application was evaluated by repeatedly analyzing reference specimens (precision evaluation) and by comparing blood concentrations in Li-treated patients assessed by ISE and flame emission spectrometry (FES) (correlation and agreement). Precision evaluation was sufficiently high. Li values determined by ISE in venous and capillary whole blood showed high correlations with FES plasma values (correlation coefficients between 0.86 and 0.99). Within the therapeutic range (0.3-1.0 mmole/l Li), agreement was sufficient for venous and less satisfactory for capillary blood (mean differences, FES minus ISE: -0.03 and 0.11 mmole/l Li). Above the therapeutic range, ISE values markedly exceeded FES results. PMID- 1461950 TI - Normal nucleolar size of entorhinal cortex cells in schizophrenia. PMID- 1461951 TI - Age and the dexamethasone suppression test: results from a broad unselected patient population. AB - We examined the relationship between age and postdexamethasone serum cortisol concentration in 676 psychiatric inpatients with a variety of DSM-III diagnoses. Regardless of diagnosis, patients 65 years and older had significantly higher nonsuppression rates than those below age 65 (64% vs. 34%). The correlation between age and cortisol level was moderate, but significant. Aging is associated with increasing nonsuppression rates to dexamethasone, and this change is augmented by an affective disorder diagnosis. Levels of nonsuppression and age cortisol correlations vary depending on dose of dexamethasone, diagnosis, and gender. PMID- 1461952 TI - Affective response to color-slide stimuli in subjects with physical anhedonia: a three-systems analysis. AB - Emotion-provoking visual stimuli were presented to college undergraduates identified as anhedonic or normal, based on their scores on the Physical Anhedonia Scale (Chapman, Chapman, & Raulin, 1976). The affective stimuli (35 mm color slides) were chosen to elicit a wide range of both positive and negative emotion, with emotional response assessed through affective judgments, viewing time, and monitoring of a variety of physiological systems (heart rate, skin conductance, and facial musculature). The experiment was successful in demonstrating differential emotional response in the two subject groups; anhedonic subjects reported a less positive response than control subjects to positive and neutral stimuli and showed no association between heart rate and the emotion content of the slides. Paradoxically, activity in the muscles of facial expression was greater in anhedonic than control subjects during the presentation of both positive and negative slides. No between-group differences were noted in the viewing-time measure. The results are discussed in the context of Lang's bioinformational theory of human emotion (Lang, 1984, 1985). PMID- 1461953 TI - Tonic and phasic electrodermal measures of human aversive conditioning with long duration stimuli. AB - Two experiments investigated phasic and tonic electrodermal responding to long, variable-duration stimuli in aversive conditioning procedures. Experiment I demonstrated reliable differential conditioning on both phasic (first interval response, FIR) and tonic (change in skin conductance level, delta SCL; spontaneous fluctuations) measures, using 10-40-s slides as conditioned stimuli (CSs) and electric shock as the unconditioned stimulus (UCS). Experiment 2 examined the sensitivity of phasic and tonic measures to UCS aversiveness. Both FIR and delta SCL were greater to a conditioned stimulus paired with shock than one paired with an innocuous reaction-time warning tone. Responding was reversed when the reinforcement contingencies were reversed. It was suggested that, with long duration CSs and an aversive UCS, phasic measures to stimulus onset, such as FIR, may reflect both stimulus significance and threat appraisal, whereas tonic measures reflect primarily arousal or anxiety arising from anticipation of the aversive unconditioned stimulus. PMID- 1461954 TI - Fearfulness and startle potentiation during aversive visual stimuli. AB - Recent experimental research suggests an association between negative affect and potentiation of the human startle reflex, as well as enhancement of this effect among fearful compared to low fear subjects. In the present study, 32 undergraduates were selected for high or low total Fear Survey Schedule scores. Acoustic startle probes were presented while subjects received warned presentations of aversive and neutral photographic slides. High fear but not low fear subjects showed potentiated short-latency cardiac acceleration and blink magnitude, and reduced blink latency, during aversive compared to neutral slides. These results support the hypothesis that affective modulation of startle is enhanced among high fear compared to low fear subjects. Considered in the context of prior findings, the results suggest that this individual difference effect generalizes across psychophysiological components of the startle reflex and diverse procedures for manipulating affect. PMID- 1461955 TI - Concomitant heart rate and eyeblink Pavlovian conditioning in human subjects as a function of interstimulus interval. AB - Pavlovian heart rate and eyeblink conditioning were simultaneously assessed in human subjects. Tone durations of 0.6, 1.1, and 2.1 s were employed in separate groups of subjects as the conditioned stimulus. A 100-ms corneal airpuff, which served as the unconditioned stimulus, overlapped the last 100 ms of the tone in each group, thus producing interstimulus intervals of 0.5, 1.0, and 2.0 s. Other groups of pseudoconditioning subjects received explicitly unpaired tone and airpuff presentations of identical durations but in a pseudorandom sequence so that they never occurred together. The best eyeblink conditioning was observed in the group with the .5-s interstimulus interval, although the 1.0-s group also demonstrated some evidence of eyeblink conditioning. The group with the 2.0-s interstimulus interval showed a lower overall rate of conditioned response occurrence and the highest rate of pseudoconditioned responding. The conditioned heart rate response in all three conditioning groups consisted of cardiac decelerations, but tone-evoked cardiac accelerations were observed in the pseudoconditioning groups. The magnitude of the cardiac deceleration was comparable in all three conditioning groups. PMID- 1461956 TI - Taking attention to task: P300, task response probability, and within-category deviation detection. AB - Previously, we reported enhanced P3 amplitudes to between-category deviations among high and low probability events. Here, we tested the effects of a within category difference. Subjects performed a go/no-go button press task as they viewed repeated, randomly-ordered presentations of nine double-digit numbers. Eight numbers fell within a prescribed range (42-49, standards); prior to testing, subjects selected one standard number for later recall. A ninth, out-of range (91, deviant) number was also included. Subjects were tested under two conditions, in which they responded either to one (low response probability) or to seven (high response probability) standard nonselected numbers, designated as targets. Relatively larger P3s were consistently apparent only when the deviant nontarget was associated with a low probability response to a nontarget. There was a selective effect of nontarget response probability on P3 amplitude to the deviant nontarget. Our results indicate that within-category deviation detection is facilitated by "controlled" attention to the structure of the stimulus field. PMID- 1461957 TI - Word frequency and multiple repetition as determinants of the modulation of event related potentials in a semantic classification task. AB - We recorded event-related potentials while subjects performed a category membership decision task. The stimuli were words of high and low frequency of occurrence in written English, and each was presented four times. The experiment was intended to explore the interaction of word frequency and multiple repetition on the event-related potential, and thence to investigate the possible loci in time of the effects of these variables. First presentations of low and high frequency words evoked event-related potentials which differed in the presence, in the low word frequency waveforms, of a right-hemisphere dominant negativity peaking at 400 ms. This negativity was very similar to the N400 which may be sensitive to the semantic relations among words in a sequence. Initial repetition diminished this midlatency difference, but gave rise to both earlier and later frequency-related differences. Subsequent multiple repetition abolished the early frequency-related repetition effect, but did not affect amplitudes in the region of N400, nor did it abolish a late positivity, present only for repeated low frequency words. PMID- 1461958 TI - Interactive effects of difficulty and instrumentality of avoidant behavior on cardiovascular reactivity. AB - College-aged subjects performed 35 trials of an easy or difficult digit recognition task. Half were told that a good performance would ensure a high chance of avoiding a blast of noise, and half were told that a good performance would ensure a low chance of avoiding the noise. Results indicated that heart rate and systolic blood pressure reactivity were higher in the difficult condition than in the easy condition only when the probability of avoiding the noise (given success) was high. When the probability of avoiding the noise (given success) was low, heart rate and systolic responsivity were low regardless of task difficulty. It also was found that (1) performance quality was poorer overall among difficult subjects than among easy subjects, and (2) that the difference in performance quality between the easy and difficult groups was somewhat (not significantly) greater in the low-probability conditions than in the high-probability conditions. Major findings are considered in terms of Obrist's reasoning regarding the psychophysiological consequences of active coping and a motivational model by Brehm, which specifies conditions under which individuals will be more and less task engaged. PMID- 1461959 TI - Analysis of pattern-reversal visual evoked-potential topography: replicability in normal subjects and comparisons with Alzheimer's disease. AB - This paper reports two studies using multivariate analysis to aid the interpretation of cross-coherence of multiple electrode sites in evoked potential responses. In the first study, the replicability of principal components and multidimensional scaling was evaluated by applying both methods to pattern reversal visual evoked potentials recorded from 28 scalp sites in two subgroups of sex- and age-matched healthy subjects, and then comparing the results. Four dimensions replicated in the two initial multidimensional scaling solutions and appeared to reflect differences in: 1) anterior versus posterior scalp areas, 2) laterality, 3) separation of frontal and occipital sites from other scalp regions, and 4) proximal versus distal placements. The initial principal components did not match well in the two groups, but rotation to congruence improved their replicability and ultimately yielded axes similar to those of the multidimensional scaling dimensions. In the second study, Alzheimer's disease and sex- and age-matched control subjects were evaluated. The four axes identified were the same as those described above, but after the solutions were rotated to align them, the group differences appeared negligible. Examination of the components and dimensions from both studies showed some consistent departures from being merely reflectors of site location, and the apparently visual dimension appeared clearly in all four groups. Judged on the basis of initial interpretability and replicability of the solutions, the results suggest that multidimensional scaling, with appropriate transformation, may provide an effective tool for analyzing pattern-reversal visual evoked-potential topography. PMID- 1461960 TI - Comparison of impedance cardiographic measurements using band and spot electrodes. AB - The comprehensive assessment of cardiac function using impedance cardiography has led to increasingly widespread use of the technique in psychophysiology. Disposable adhesive band electrodes have been the most widely used electrode type, but spot electrode configurations present attractive alternatives in terms of convenience and subject comfort. The present study was designed to evaluate whether one such spot electrode configuration yielded the same information as the more standard band electrodes for cardiac output and systolic time interval measurement. Male and female healthy adult subjects (N = 20) were tested. Comparisons between spot and band electrodes were made for the absolute magnitude of cardiac output and systolic time intervals, as well as for responses to the highly reproducible effects of bicycle exercise. Consistent with previous findings, systolic time interval measurements were unaffected by electrode type. However, for cardiac output measurements, differences between spot and band electrode measurements were found. Under resting conditions, the absolute magnitudes of cardiac output values measured using spot electrodes were smaller than for band electrodes. Subtle, yet significant differences were also found for cardiac output responses to exercise, with spot electrodes indicating greater increases in cardiac output than band electrodes. At the same time, anticipated gender differences found for cardiac output at rest and in response to exercise were unaffected by electrode type. Overall, these findings suggest that when comparing the results of studies that have utilized different impedance electrode types, it would be prudent to remain alert to the possibility of confounding influences. PMID- 1461961 TI - Alternate cardiovascular baseline assessment techniques: vanilla or resting baseline. AB - The accurate evaluation of cardiovascular reactions to psychological challenge requires stable baselines against which change can be evaluated. When more than one challenge is employed, the recovery of this baseline becomes important in order to avoid carryover effects. Resting periods, even those of 20 min or more, do not guarantee baseline stability. We compared a 20-min resting condition and a new form of baseline condition in 48 college men using video tasks as the psychological challenges. The new form was a minimally demanding color detection task, termed the "vanilla" baseline condition. A 10-min version and a 20-min version of this condition were tested. Comparisons to 10-min resting baselines were made using our prior work and values from the literature. Vanilla baseline conditions were shown to be equal to or better than resting baseline conditions using criteria of between- and within-baseline stability, amplitude and significance of responsivity, and generalizability between sessions on separate days. Ten-minute resting baselines also showed acceptable stability, questioning the value of lengthy baselines. The good performance of the 10-min vanilla baseline in initial and replication samples supported its utility for estimating baselines for many purposes. PMID- 1461962 TI - Developing a level III/IV medical/psychiatry unit. Establishing a basis, design of the unit, and physician responsibility. AB - This article is part of a series defining the administrative, logistical, and funding issues necessary for the establishment of a medical/psychiatry unit. It emphasizes the experience of individuals who have developed such units and is offered in an attempt to prevent duplication of costly mistakes. Administrative issues, factors affecting the physical design of the unit, requirements for medical coverage and medical and psychiatric programmatic support, and the ethical issues encountered in managing such a unit are discussed. PMID- 1461963 TI - Categorization of types of medical/psychiatry units based on level of acuity. AB - Medical/psychiatry units can be categorized by the level of acuity of medical and psychiatric illness. Type I units are categorized as those that primarily provide psychiatric care with a low level of medical acuity. Type II units include general medicine or medical subspecialty units that are associated with a psychiatric liaison service and provide low levels of psychiatric care to those admitted to the general medical setting. Type III and Type IV units are characterized by a true departure from the current ward settings and care for patients who have concurrent and more severe medical and psychiatric problems in a unified setting. Both of these units require special physical changes in the ward structure, additional nurse training, and coordinated physician coverage to function effectively. PMID- 1461964 TI - Quality assurance in a setting designed to care for patients with combined medical and psychiatric disease. AB - In an attempt to address the needs of patients with combined medical and psychiatric illness, a variety of clinical centers are now creating medical/psychiatry units. These units differ widely in their clinical capabilities, yet no adequate delineation of safeguards regarding quality of care currently exists. This article discusses minimum quality guidelines for four types of medical/psychiatry units that are based on the level of acuity of patients' medical and psychiatric disease. PMID- 1461965 TI - The chronically ill child and family stress. Family developmental perspectives on cystic fibrosis. AB - The authors take a developmental and family systems perspective in reviewing research on the family stressors inherent in caring for a child with a chronic disease. Cystic fibrosis, a genetically transmitted and life-shortening disorder, exemplifies a chronic disease that places demands on the family that are both unique and shared with other prolonged illnesses. The authors chronicle the interaction of the debilitating features of this disease and its demanding treatment regimen with family dynamics from the point of initial diagnosis to the terminal stages. PMID- 1461966 TI - An animal model for delirium. AB - This study describes an animal model for delirium comparing rats treated with either saline or atropine. The model was defined by recordings of cortical EEGs, maze performance, and behavioral observations. EEG slowing and increased amplitude, difficulty with attention and memory, sleep-wake cycle reversal, and changes in behavior (lack of focused direction, irritability, fluctuating levels of activity, excessive random sniffing) appeared consistent with signs and symptoms seen in human delirium. EEG abnormalities in atropine-treated rats returned to normal before cognitive deficits did. Motor activity monitoring did not reveal diminished motor activity as a confounding variable in maze performance. PMID- 1461967 TI - Physical symptoms and depressive symptoms among individuals with HIV infection. AB - The authors investigate the importance of physical symptoms as a correlate of depressive symptoms and suicidal thoughts in a large (N = 881) community-based sample of persons infected with human immunodeficiency virus. The study overcomes limitations of prior research by minimizing overlap in measures of affective and physical symptoms, studying a more diverse population, and including correlates such as measures of social support, function, employment, insurance coverage, and cognitive impairment in the analysis. The authors' data support the notion that in diagnosing depression in the medically ill, concern over isolating physical symptoms as either "affective" or "physical" may be exaggerated. PMID- 1461968 TI - Bulimia nervosa. Four uncommon subtypes. AB - The histories and psychological profiles of more than 500 patients meeting DSM III-R criteria for bulimia nervosa were reviewed. A total of 310 patients demonstrated the most characteristic pattern of bulimia, with finger-induced purging and occasional diet pill, diuretic, or laxative abuse. Seventeen patients reported binge eating with no self-induced vomiting but with severe laxative abuse (i.e., greater than or equal to 50 laxatives daily). A total of 126 patients reported bulimia with finger-induced purging and regular mild (i.e., 2-3 daily) laxative abuse. Eight patients reported bulimia without finger-induced purging, diuretic, or laxative abuse but with the regular abuse of ipecac as a means of inducing vomiting. Four clinical subtypes of bulimia were seen. These were overt bulimia, which occurred in 8.9% of the sample; obsessive-ritualistic bulimia, which occurred in 2% of the sample; sexually evocative bulimia (Fatal Attraction Syndrome), which occurred in 2.9% of the sample; and masochistic bulimia, which occurred in 4.9% of the sample. Each of these subtypes of bulimia are described and defined. The characteristic psychologic profile, clinical features, and implications for treatment and research are discussed. PMID- 1461969 TI - The power of statistical studies in consultation-liaison psychiatry. AB - Several authors recently have proclaimed the need for empirically based research articles in consultation-liaison psychiatry. The authors report that although the proportion of empirically based studies published in Psychosomatics increased 148% from 1979 to 1989, the power of statistical analyses and the deleterious effect of multiple tests were often neglected. A power analysis of empirical studies published in the 1989 volume year of Psychosomatics is reported, showing statistical power to be low for all but the most robust of effect sizes. PMID- 1461970 TI - Psychological modulation of the delayed type hypersensitivity skin test. AB - Considerable data have demonstrated that psychological states can influence the immune system in animals. Whether human immune function can be intentionally modulated by the central nervous system is unknown. This article presents data from two studies that sought to demonstrate intentional modulation of the immune system by psychological interventions. It also discusses the methodological complexities involved with this type of research in humans. PMID- 1461971 TI - Psychosis in a male pseudohermaphrodite with 17-hydroxylase deficiency. PMID- 1461972 TI - Zidovudine overdose in an asymptomatic HIV seropositive patient with hemophilia. PMID- 1461973 TI - Organic anxiety disorder secondary to hyperthyroidism in a hemodialysis patient. A rare occurrence. PMID- 1461974 TI - Elective removal of a transplanted organ. PMID- 1461975 TI - Impact of religious belief on psychological distress. PMID- 1461976 TI - Misidentification syndrome, facial misrecognition, and dysmorphic symptoms. PMID- 1461977 TI - Sertraline-augmented lithium therapy of organic mood syndrome. PMID- 1461978 TI - Sexually transmitted spreading of HIV infection: "bridging population" or "suckback movement"? PMID- 1461979 TI - [Radiology in intensive care medicine]. PMID- 1461980 TI - [Legionnaires' disease in intensive care patients. Results of plain film thoracic radiography]. AB - We reviewed the chest radiographs and clinical data of 30 patients in an intensive care unit with legionellosis diagnosed by significant serological findings (n = 18), microscopic demonstration of the organism in the transtracheal aspirate (n = 5) or both (n = 7) and investigated the correlation between the identification of Legionella and signs of pulmonary infection. In 13 patients legionnaires' disease was diagnosed with a high degree of confidence. Typical radiographic findings included distal air space disease, which initially appeared to be unilateral, progressing towards bilateral infiltrates. Patchy infiltration at the onset of disease was followed by consolidation. Small pleural effusions were common, while no abscess formation was observed. Characteristically, infiltration persisted for weeks even with clinical convalescence. These radiological findings correspond well with observations in otherwise healthy patients with legionnaire's disease. In 10 patients the etiology of pulmonary infiltrates could not be identified. Seven patients did not develop radiological or clinical signs of pneumonia; therefore, the serological/microscopic detection of Legionella was not interpreted as legionnaires' disease. According to the results of our investigation the diagnosis of legionnaires' disease requires radiological findings in addition to laboratory data. PMID- 1461981 TI - [An economic comparison between digital luminescence radiography and conventional film processing in intensive care medicine]. AB - The costs of a conventional film-screen radiography daylight-system and storage phosphor computed radiography (Fuji AC-1) are compared. In 1990, 3841 radiologic procedures (mostly portable chest X-rays) were performed in 3474 patients of a surgical intensive care unit. With conventional film-screen radiography 6.8% retakes were necessary for diagnostic or technical reasons. Comparing the fixed and variable costs of both systems conventional film-screen radiography was more economic under the given conditions of the test. It is concluded that computed radiography in intensive care patients has definite advantages in terms of image quality and reproducibility, however, in order to compete successfully in the economic turf CR has to be implemented in a picture archiving and communication system (PACS). PMID- 1461982 TI - [The x-ray clinical picture and evaluation criteria of implantable cardioverter defibrillator systems]. AB - Since the first implantation of an automatic cardioverter defibrillator (ICD) in February 1980, the therapy of ventricular tachyarrhythmia has been changed drastically. The original therapy with antiarrhythmic agents has been increasingly replaced by the implantation of the ICD. The radiologist should be aware of the different types of ICDs and their normal appearance, because thorax radiography is often used during regular routine follow-up of the ICD system. The different types of ICDs, their normal radiological appearances, the indications and the implantation technique are discussed in the present study. The radiologist has to interpret the radiographs with respect to the electrodes, the device and changes in heart configuration. Major migration of electrodes is visible, but the detection of little changes in configuration is only possible with the help of serial radiographs. If extraperitoneal placement of the device is suspected, an ultrasound examination should be obtained. An important complication for the radiologist is a possible deactivation of some devices by electromagnetic interference. PMID- 1461983 TI - [Splenic complications in inflammatory pancreatic diseases]. AB - Pancreatitis in combination with splenic and vascular complications is dangerous and potentially lethal. The most common complications are intestinal or intraperitoneal hemorrhage resulting directly from either vascular changes, such as erosion of the splenic artery, formation of a pseudoaneurysm, hemorrhage into a pseudocyst, or rupture of a pseudocyst with perforation into the colon, or complications in the spleen, such as anemic or hemorrhagic infarction, abscess or rupture. CT is the method of choice for the diagnosis of splenic complications of pancreatitis. Angiography is indicated in every severe hemorrhage in the presence of pancreatitis, to demonstrate vascular changes and to localize the source of hemorrhage. In addition, acute arterial bleeding can be successfully treated with catheter embolization. PMID- 1461984 TI - [Radiologic diagnosis of maxillary sinus aspergillosis]. AB - Aspergillosis of the maxillary sinuses shows an increasing incidence in even otherwise healthy patients. Next to inhalation as the mode of infection, a dental root canal filling with an orosinusal fistula can be the cause. As most infections remain initially undetected or underestimated as common sinusitis, early diagnosis must be achieved. Standard X-ray of the paranasal sinuses, conventional tomography as well as CT scans are of major importance. Centrally located hyperdense opacifications are a good criterion and can be best seen in CT. Even when the case has not progressed too much, radical surgery combined with Amphotericin B therapy is still the treatment of choice since the infection may progress rapidly. PMID- 1461985 TI - [Diagnosis of pulmonary sarcoidosis using high-resolution computed tomography]. AB - This report deals with 24 patients with pulmonary manifestations of sarcoidosis who were examined by means of high-resolution computed tomography. The characteristic findings were rounded masses of all sizes and shapes. Other findings were ground glass opacities and thickened septal walls. In the advanced stage fibrous strands and intrapulmonary cavities could be seen. High-resolution tomography allows better detection of fine granulomas and better recognition of their anatomic relationship to the pulmonary substructures, facilitating differential diagnosis against other interstitial lung diseases. PMID- 1461986 TI - [Pulmonary arteriovenous fistulas in Osler's disease]. AB - In a retrospective study over a period of 10 years we found 16 patients with Osler's disease and associated pulmonary arteriovenous fistulas in the hospital of the University of Heidelberg and the Thoraxklinik Heidelberg-Rohrbach. We report about the radiologic diagnostic findings and the clinical manifestations of this defined pulmonary malformation. Radiologic findings are round or oval lobulated homogeneous masses. The size ranges from < 1 to several centimeters in diameter, most fistulas were located in the lower lobes. Feeding and draining vessels can be identified frequently on plain radiographs or tomograms/CT. Best procedure to recognize these malformations is the selective pulmonary arterial angiography. PMID- 1461987 TI - [An unusual space-occupying lesion as a cause of an acute abdomen. An acute hemorrhage from a myelolipoma]. PMID- 1461988 TI - Insulin, insulin-like growth factors and glucose transporters: temporal patterns of gene expression in early murine and bovine embryos. AB - mRNA phenotyping by the reverse transcription-polymerase chain reaction (RT-PCR) method was used to compare the patterns of expression of insulin and insulin-like growth factor (IGF) ligand and receptor genes in preimplantation bovine embryos with those established previously for preimplantation murine embryos. In the early bovine embryo, transcripts for IGF-I, IGF-II and mRNAs encoding receptors for insulin, IGF-I and IGF-II were all detectable at all embryo stages from the 1 cell zygote to the blastocyst. In the mouse, IGF-II ligand and receptor mRNAs were not expressed until the 2-cell stage, and the insulin and IGF-I receptor mRNAs were not detectable until the 8-cell stage. Since transcriptional activation of the embryonic genome occurs at the 8- to 16-cell stage in the bovine embryo and at the 2-cell stage in the murine embryo, it is suggested that these transcripts are products of both the maternal and embryonic genomes in the bovine embryo whereas in the mouse they are present only after activation of the embryonic genome. Transcripts for insulin were not detected in preimplantation embryos of either species. Colloidal-gold immunocytochemistry with antibodies directed against the insulin receptor, IGF-I receptor and IGF-I ligand has confirmed the presence of these molecules in bovine blastocysts. RT-PCR and indirect immunofluorescence procedures demonstrated that the glucose transporter (GLUT) isoform 1 is present in murine embryos from the oocyte to blastocyst stage whereas GLUT 2 expression begins at the 8-cell stage. PMID- 1461989 TI - Insulin and the insulin-like growth factors (IGFs) in preimplantation development. PMID- 1461990 TI - Metabolic and developmental responses of preimplantation embryos to platelet activating factor (PAF). AB - Platelet activating factor (PAF) is an ether phospholipid produced by preimplantation embryos of a number of species. Production of PAF by embryos has been measured by detecting thrombocytopenia in a splenectomized mouse bioassay, platelet aggregation bioassays in vitro and a specific radioimmunoassay. Production is highly variable and is adversely affected by culture in vitro. It has, however, been correlated with morphology, development rates in vitro and the pregnancy potential of embryos following transfer. Investigations using PAF antagonists have established an essential role for PAF in early pregnancy. Together with studies that have shown PAF to have direct effects on embryonic metabolism during culture in vitro, these observations suggest that PAF acts as an embryonic autocoid. Hence, a major site of action for embryo-derived PAF in vivo is the embryo itself. Supplementation of embryo culture media with PAF had no effect on the rate of development in vitro of 2-cell mouse embryos through to the blastocyst stage. However, PAF increased cell numbers of blastocysts cultured from the 2-cell stage and the mitotic index of embryos at both the 8-cell and blastocyst stages. Supplementation of culture media with PAF has also been shown to increase the implantation potential of both mouse and human embryos cultured in vitro. In the mouse, the effect of PAF in enhancing implantation rates was most evident when the developmental potential of untreated embryos was suboptimal. These observations suggest that the production of embryo-derived PAF is one limiting factor in maintaining the viability of embryos cultured in vitro. PMID- 1461991 TI - Actions of platelet activating factor (PAF) on gametes and embryos: clinical aspects. AB - Platelet activating factor (PAF) is a phospholipid widespread in body tissues. Previous reviews have discussed its production by preimplantation embryos and the evidence implicating it as an autocrine mediator in aspects of gamete and embryo physiology. Human spermatozoa contain variable amounts of PAF, the amount contained depending on the source and method of preparation of the sperm. Incubation of human sperm with PAF tends to increase their forward velocity, especially in samples with slow motility. PAF treatment causes an increase in the proportion of acrosome-reacted sperm and in their ability to penetrate both zona free hamster ova and cervical mucus. PAF has been found in human follicular fluid at ovulation. A role for PAF in ovulation has been suggested, because PAF antagonists reduce the rate of ovulation in rats. In some studies, modest improvements to mouse in vitro fertilization (IVF) rates have been achieved with PAF supplementation of media under specific conditions. Furthermore, in the rabbit and mouse, PAF antagonists have been reported to inhibit fertilization in vivo and in vitro respectively. However, addition of PAF to human IVF medium, but only at the time of insemination and fertilization, had no effect on either fertilization or pregnancy rates. Sensitive bio- and immuno-assays have shown that PAF is secreted by human embryos into their fluid milieu. PAF secretion by these zygotes during culture, although markedly variable, has been correlated with the achievement of pregnancy and pregnancy outcome. Although the secretion of PAF by the mouse embryo decreases during culture in vitro, exogenous PAF enhances embryo viability during culture. Similarly, culture of human zygotes in PAF-supplemented medium prior to embryo transfer significantly increases the chance of achieving pregnancy. Both the implantation and live-birth rates are increased in human IVF by addition of PAF to the medium. PMID- 1461992 TI - Early pregnancy factor has immunosuppressive and growth factor properties. AB - Early pregnancy factor (EPF) was first described as a pregnancy-associated substance, although recent studies suggest a more general link with cell development. It is a product of actively dividing cells and its apparent functional importance to them suggests its potential as a regulator of cell proliferation. The recent discovery of EPF in platelets has provided a comparatively rich and readily available source of EPF. The purification procedures employed to isolate EPF from this source have also been applied to pregnancy serum and urine, medium conditioned by oestrous mouse ovaries (stimulated with prolactin and embryo-conditioned medium), medium conditioned by tumour cells, and serum from rats 24 h after partial hepatectomy (PH). In all instances, biological activity followed the same pattern throughout. Furthermore, the final active reversed-phase high-performance liquid chromatography fraction from all sources was bound specifically by immobilized anti-EPF monoclonal antibodies (MAbs), indicating that the active fractions produced from these diverse sources are very closely related, if not identical. Some differences have been observed in the behaviour of EPF in various conditions. EPF is produced by proliferating tumour cells and by liver cells post-PH, and passive immunization studies with anti-EPF MAbs have shown that these cells need EPF for survival. In contrast, EPF has not been detected as a product of the pre-embryo, and addition of anti-EPF MAbs to embryo cultures does not adversely affect development from the 2-cell to the blastocyst stage. Although the pre-embryo is not dependent on EPF for its development in vitro, neutralization of EPF in vivo by anti-EPF MAbs retards its development. Thus, EPF appears to play an indirect role in maintaining the pre-embryo. By virtue of its ability to suppress the delayed-type hypersensitivity reaction, it has been suggested that EPF might act as an immunological response modifier of the maternal immune system. Alternatively, the effect of EPF on lymphocytes may be to reduce the expression of all or some cytokines and this could inhibit development. Whether or not EPF acts more directly as an autocrine growth factor from around the time of implantation, when the embryo first begins synthesis of EPF, is not known and remains to be investigated. PMID- 1461993 TI - Identification of molecules and mechanisms involved in the 'early pregnancy factor' system. AB - For a long time the 'early pregnancy factor' has defied molecular definition. First described in 1976, this phenomenon is revealed in vitro by the rosette inhibition assay, in which a lymphocyte-modifying activity in maternal serum is detected within hours of fertilization; it is present for at least the first two thirds of pregnancy, with continued detection dependent upon the presence of a viable embryo or fetus. It has potential applications in early pregnancy testing, for monitoring fetal well-being and in the study of fertility control. Although the activity detected is one of a complex biological fluid (pregnancy serum) in a complex biological assay, this ability of pregnancy sera to cause increased rosette inhibition titres (RIT) has generally been ascribed to the presence of an 'early pregnancy factor' (EPF). The common usage of the term EPF has implied the existence in pregnancy sera of a unique factor, which has often been assumed to be a novel, pregnancy-specific protein with the unique capacity to induce increased RITs. Recent results render this concept untenable. These studies have begun to identify the molecules and mechanisms which cause the expression of increased RITs. In particular, thioredoxin or thioredoxin-like molecules have been identified as involved in the mechanisms by which pregnancy sera induced increased RITs. As a result, a new paradigm for the EPF phenomenon is presented which helps to resolve many of the enigmatic properties previously ascribed to the so-called 'early pregnancy factor' and which may assist in the further understanding of the molecular mechanisms of communication between embryo and mother prior to implantation. PMID- 1461994 TI - Granulocyte-macrophage colony stimulating factor (GM-CSF): one of a family of epithelial cell-derived cytokines in the preimplantation uterus. AB - Granulocyte-macrophage colony stimulating factor (GM-CSF) is one of a number of lympho-haemapoietic cytokines, including CSF-1, interleukin-6 (IL-6) and leukaemia inhibitory factor (LIF) now known to be synthesized by epithelial cells in the murine uterus. GM-CSF synthesis is regulated primarily by the ovarian steroid hormone oestrogen, but is also subject to modulation by factors including a seminal component of seminal vesicle origin which stimulates a 20-fold increase in luminal fluid content at mating, and bacterial lipopolysaccharide (LPS) and the T-lymphocyte and natural killer (NK) cell product interferon-gamma (IFN gamma). In the non-pregnant mouse GM-CSF synthesis peaks at oestrus. Synthesis is maintained at comparable or moderately higher levels during the preimplantation period of pregnancy and in the non-decidualized endometrium during mid gestation. An embryotrophic activity is suggested by studies in vitro that indicate that GM CSF stimulates attachment and outgrowth of blastocysts. It is postulated that GM CSF is of major importance to the physiology of pregnancy through its role as a component of a local cytokine circuit acting to recruit and regulate function of endometrial leukocytes, and by its action as interlocutor and important effector arm in embryo-maternal interactions during gestation. PMID- 1461995 TI - The effect of leukaemia inhibitory factor (LIF) on embryogenesis. AB - Leukaemia inhibitory factor (LIF) was originally identified as a haemopoetic factor that induced the differentiation of certain myeloid leukaemia cell lines. In contrast to this action, LIF was subsequently shown to inhibit the spontaneous differentiation of murine embryonic stem cells in culture, thus maintaining their pluripotency and ability to contribute to the germline of chimaeric mice. In the mouse, mRNA for LIF is expressed by the endometrial glands of the uterus coincident with the time of blastocyst implantation and receptors have been found on the preimplantation blastocyst. The signal for LIF expression appears to be of maternal origin, perhaps regulated by oestradiol. Recombinant LIF improves the development of murine and ovine blastocysts in culture although there is some species specificity with respect to the type of LIF that is bioactive. It is proposed here that LIF acts on the trophectoderm of the rapidly expanding blastocyst and improves the implantation rate of otherwise compromised embryos. Further studies in livestock should elicit therapeutic uses for LIF in embryo culture, embryo transfer and embryo survival in vivo. PMID- 1461996 TI - Effects of hypoxia on morphological and biochemical characteristics of renal epithelial cell and tubule cultures. AB - Apoptotic cell death plays an important role in the pathogenesis of renal atrophy in diseases of the kidney involving chronic mild ischemia. The present study constitutes an in vitro model of these diseases and assesses the modes of cell death involved after hypoxic treatment of renal epithelium. Cultures of MDCK cells or primary cultures of rat renal parenchymal tubules were treated in either a physiological or a hypoxic atmosphere. Cultures were collected before treatment and at 24 h and 48 h, for morphological and biochemical studies. Both apoptosis and necrosis were observed at significantly increased levels by 48 h of hypoxia in the MDCK cell cultures. DNA gel electrophoresis patterns supported these findings. Experiments using tubule cultures demonstrated that, during the 48 h of study, tubular epithelial cells in the center of the control tubule structures died by apoptosis, possibly as a result of mild oxygen and/or nutrient depletion. With added hypoxic treatment, however, the entire tubule structure became necrotic. Results are similar to those found during in vivo studies, thus providing in vitro models that may be developed further to define factors in the pathogenesis of some renal diseases. PMID- 1461997 TI - Ischemia-reperfusion induced acute renal failure in the rat is ameliorated by the spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN). AB - The spin-trapping agent alpha-phenyl-N-tert-butyl nitrone (PBN) reduced the ischemia-reperfusion induced acute renal failure in the rat. Renal ischemia was produced in unilateral nephrectomized rats by complete occlusion of the left renal artery for 60 min. Perfusion of the kidney was then reestablished, and the rats were sacrificed 48 h later. PBN (100 mg/kg i.p.) administered 30 min prior to renal artery occlusion significantly reduced the increase in serum creatinine and urea and renal failure index, as well as the decrease in urine/plasma creatinine ratio and creatinine clearance compared to saline-injected ischemic rats. PBN injected to control rats had no effect on these parameters. These data support the hypothesis of an involvement of reactive free radicals in the pathogenesis of ischemia-reperfusion induced acute renal failure in the rat and suggest that PBN may be a useful agent for the prevention of renal ischemia reperfusion damage. PMID- 1461998 TI - Alterations of gluconeogenesis by ischemic renal injury in rats. AB - This study was designed to determine changes in one metabolic function, gluconeogenesis (GLG), after ischemic renal injury. Tubule suspensions were prepared by collagenase treatment of SD rat kidneys on 1, 3, and 7 days after left renal artery and vein occlusion for 0-90 min and incubated in Krebs Henseleit buffer with or without 2 mM pyruvate or malate aerobically. Glucose contents were assayed photometrically. On days 1 and 3 after ischemia for longer than 60 min, serum creatinine levels rose significantly. The tendency of increase of GLG was observed on days 1 and 3 after 10-60 min of ischemia. GLG increased significantly on day 1 after 30-min ischemia. On the other hand, GLG decreased significantly on day 1 after 90-min treatment. Morphologic damage was limited to the corticomedullary region on days 1 and 3 after ischemic times of 30 and 60 min. These results suggest that renal GLG is stimulated to supply energy for ATP decrease by ischemia and for further regeneration in extraproximal segments along the nephron. PMID- 1461999 TI - Reduction of CyA nephrotoxicity by nifedipine during and after experimental in situ renal preservation. AB - In order to evaluate the role of nifedipine in the nephrotoxic effect induced by both ischemia and CyA, 18 healthy mongrel dogs were used. The kidneys were exposed and subjected to 1 h of ischemia by clamping both renal vessels. To the renal artery of the first group of kidneys (n = 9), 300 mL of cold Euro-Collins solution, in which nifedipine (Bay a 1040-10 mg) was diluted, was infused for 15 min (nifedipine group), while 300 mL of cold Euro-Collins solution plus 10 mg of placebo (Bay a 1040-placebo) was infused to the renal artery of the second group (n = 9) of kidneys (placebo group). Venous drainage was effected through a plastic cannula. All animals received through a nasogastric catheter 20 mg/kg cyclosporine A at the beginning of the ischemia. The 1 h of ischemia was divided in a 15-min period of cold ischemia and 45-min of warm ischemia, at the end of which the clamps were removed. During the 2 h (30 min x 4) after reperfusion, 10 mg of nifedipine and placebo was administered additionally by a peripheral vein to the nifedipine and the placebo group, respectively. Then the kidneys were removed for histological study. Urine volume and creatinine and urea clearances of the nifedipine group were significantly higher than the placebo group (p < 0.001) while TxB2 levels were higher in the placebo group in all studied periods (p < 0.001). Urine sodium, FENa, osmolar clearance, and LDH values were significantly different (p < 0.01), but the urine potassium concentration was not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462000 TI - Acute cyclosporin A renal dysfunction in dogs reversed by calcium antagonists and antiplatelet agents. AB - The aim of this study was to assess the effect of nifedipine and piracetam alone or in combination in the protection of renal function and morphology after cyclosporin A (CyA) administration. Thirty healthy mongrel dogs with a mean body weight of 15 kg were sacrificed. Six animals (group C) were given CyA 20 mg/kg body weight per os, while the remaining groups (8 animals each) were given concomitantly 20 mg nifedipine (group CN) or 4 g of piracetam (group CP), or both drugs in combination (group CNP). After 5 days of drug administration the animals were anesthetized, both kidneys were exposed, and functional tests were performed. Then the kidneys were removed for histological study. The mean plasma CyA levels in the four groups were 1765 +/- 685 ng/mL, 1300 +/- 324 ng/mL, 1116 +/- 491 ng/mL and 1600 +/- 290 ng/mL, respectively. Urine volume, creatinine, urea, and osmolar clearances were significantly higher in the groups CN, CP, and CNP compared to the control group C (p < 0.01). Urine sodium concentration was significantly higher (p < 0.05 or p < 0.01) in nifedipine groups than in the other two groups of animals, while the fractional excretion of sodium (FENa%) was significantly higher (p < 0.01) in all treated groups compared to controls. Plasma thromboxane-B2 levels were significantly reduced by each drug alone or in combination (p < 0.01). Morphological lesions, similar in all groups, did not correlate with the functional improvement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462001 TI - Effects of desoxycorticosterone acetate (DOCA) plus saline drinking on gentamicin mediated nephropathy in rats. AB - Studies were performed to examine the effect of desoxycorticosterone acetate (DOCA) treatment plus isotonic saline drinking on gentamicin (GM)-mediated nephropathy in rats. GM, 40 mg/kg/day, was subcutaneously injected for 13 days following a 5-week treatment with water drinking or DOCA (10 mg/kg/week) plus saline drinking. Twenty-four hours after the last injection of GM, renal blood flow (RBF) and Cin decreased to approximately 69% and 52% of the control values in water-drinking GM-treated rats, respectively, but was well maintained in DOCA plus saline-drinking GM-treated animals. There was no significant difference in morphologic tubular injury or the renal cortical GM content between GM-treated groups. Saline drinking alone (1% saline, 5 weeks) lessened neither GM-induced reduction in GFR nor tubular damage. Body weight loss occurred following GM injection in the water-drinking group but not in the DOCA plus saline-drinking and saline-drinking-alone groups. DOCA plus saline drinking significantly suppressed the plasma renin activity (PRA) but saline drinking alone did not. A significant inverse correlation was found between PRA and Cin in water-drinking GM-treated and untreated rats. The data suggest that the beneficial effect of DOCA plus saline drinking is associated with renin-angiotensin suppression rather than with the renal GM content or well-maintained hydration. PMID- 1462002 TI - Tubular injury and regeneration in the rat kidney following acute exposure to gentamicin: a time-course study. AB - Aminoglycoside antibiotics act as nephrotoxic drugs, inducing a lysosomal phospholipidosis and necrotic lesions essentially in convoluted proximal tubules. Previous studies have demonstrated that tubular injury caused by these compounds elicits a process of renal tissue repair (tubular regeneration) involving an increase of cell turnover in tubular epithelium. The present study was performed in order to: (i) achieve further insight into the temporal relationship between aminoglycoside-induced phospholipidosis, tubular necrosis, and tubular regeneration; and (ii) approach the control of tubular regeneration after nephrotoxin-induced insult. To investigate the latter point, we examined by immunocytochemistry the intrarenal distribution of epidermal growth factor (EGF) during tubular regeneration. Five groups of female Sprague-Dawley rats (n = 5) were treated for 4 days with gentamicin i.p. at a daily dose of 50 mg/kg delivered in 2 injections per day. Sham-treated animals (n = 5) received an equivalent amount of vehicle (0.9% NaCl) according to the same protocol. Groups of treated rats, and controls, were terminated 16 h (day 1), 4 days, 7 days, 14 days, and 21 days after the end of gentamicin administration. One hour prior to necropsy, each animal was given an i.p. injection of 40 mg 5-bromo-2' deoxyuridine (BrdU) for the immunocytochemical demonstration of S-phase cells, using an anti-BrdU monoclonal antibody. Renal tissue was processed for light microscopy analysis, namely: a computer-aided morphometry of lysosomes in proximal tubular cells, a single-blind evaluation of gentamicin-induced tubular injury, the measurement of cell proliferation by immunocytochemical detection of BrdU-labeled nuclei, the demonstration of EGF-like immunoreactive material in renal tissue by using anti-rat EGF antiserum and immunogold-silver staining. As revealed by the morphometry of lysosomes in proximal tubular epithelium, the degree of gentamicin-induced phospholipidosis was maximum at day 1 (relative area occupied by lysosomes was increased 25-fold over mean control value) and declined thereafter. In contrast, tubular necrosis reached a peak 4 days after the end of drug administration. In proximal tubular epithelium, the stimulation of cell turnover associated with tubular regeneration showed a peak at day 7 (15-fold the mean control value). Tubular regeneration was also accompanied by mild interstitial hyperplasia. Three weeks after treatment with gentamicin, morphological evidence of drug-induced injury had disappeared due to the tissue repair process, except for the occasional presence of small hyperplastic foci in renal cortex interstitium. In both treated animals and controls, EGF immunoreactivity as revealed by immunocytochemical staining was associated with distal tubules (renal cortex and outer medulla).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1462003 TI - Activity of serum enzymes in puromycin aminonucleoside-induced nephrotic syndrome. AB - Total serum protein, serum albumin, total urine protein excretion, and the serum activity of several enzymes--aldolase (ALS), cholinesterase (CHS), leucine aminopeptidase (LAP), isocitrate dehydrogenase (ICD), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha hydroxybutyrate dehydrogenase (HBD), creatine kinase (CK), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT)--were estimated in rats with nephrotic syndrome (NS) at 2, 4, 6, 8, 10, 12, 16, 20, and 30 days after a single injection of puromycin aminonucleoside (PAN). It was found that: (a) total serum protein and serum albumin diminished on day 4 and returned to control values on days 20 and 30, respectively; (b) total urine protein excretion rose on day 4, reached a peak value on day 8, and then fell substantially but still remained higher than control values on day 30; (c) ALS and CHS activities increased; (d) LAP, ICD, and AST activities showed a biphasic pattern, first increasing and then decreasing; (e) ALT, LDH, HBD, CK, and ALP activities decreased; and (f) GGT activity remained unchanged. The differences in the profiles of the enzyme activities suggest their independent regulation in experimental NS induced by PAN. PMID- 1462005 TI - Thrombocytopenia in renal failure in a developing country. AB - A retrospective study over a 3-year period was done looking at predialysis platelet levels, in particular, thrombocytopenia. Seventy-five patients with acute renal failure (ARF) and 75 patients with chronic renal failure (CRF), treated at King Edward VIII Hospital, were randomly chosen. Platelet counts were performed on a coulter counter (S + 2) and counts of less than 150 x 10(9)/L were considered as thrombocytopenia. Of the 75 CRF patients, 47 were males. Eleven (14.7%) were thrombocytopenic with a mean platelet count of 118.3 x 10(9)/L and a range of 83-146 x 10(9)/L. The mean creatinine level was 1510 micrograms/L. The remaining nonthrombocytopenic patients had a mean platelet count of 268 x 10(9)/L and a mean creatinine of 1080 micrograms/L. Of the ARF patients, 39 were males. Twenty-two (29.3%) had thrombocytopenia with a mean platelet count of 98 x 10(9)/L and a range of 22-147 x 10(9)/L. The mean creatinine level was 819 micrograms/L. The remaining nonthrombocytopenic patients had a mean platelet count of 319 x 10(9)/L and a mean creatinine of 1020 micrograms/L. In CRF patients no correlation was found between thrombocytopenia and the disease process. Creatinine levels appear to be higher in the thrombocytopenia group than in the nonthrombocytopenic group. In the ARF group of patients, females had a higher frequency of thrombocytopenia than males. Obstetrical and gynecological causes and herbal ingestion were the 2 major underlying etiologies in the thrombocytopenic group. Thrombocytopenia appears to be a common presenting feature in ARF as opposed to CRF, and this may be accounted for by the underlying etiologies in ARF. PMID- 1462004 TI - IgA nephropathy: acute renal failure, acute tubular necrosis, and features of postinfectious acute glomerulonephritis. AB - From 1976 to 1987 on our Nephrological Unit, 57 patients with IgA nephropathy (IgAN) proven by renal biopsies were found. Three of those presented with acute tubular necrosis (ATN) and glomerulitis, without extrarenal predisposing cause in two; and showed, as prominent manifestation, a severe acute renal failure syndrome (ARFS), needing dialytic treatment. All three had hematuria, which was macroscopic in two and microscopic in one. Thus the prevalence of the association of glomerulitis and ATN was about 5.2%. There was complete recovery of renal functions in all three patients, but the usual symptomatology of IgAN. Two patients presented polymorphonuclear neutrophils infiltration of glomerular capillaries and in one of them, electron-dense deposits on the epithelial side of glomerular basement membrane ("humps") were observed, as well as those identified in the mesangial area. The glomerular polymorphonuclear neutrophils infiltration and endothelial cells proliferation (cases 1 and 3), the presence of "humps" (case 1), high antistreptolysin O (ASO) titers (cases 1 and 2), and low serum complement levels (case 1), suggest the possibility that antigens able to cause postinfectious glomerulonephritis (streptococcal or not) could induce in some individuals, by another immunopathogenetic route, mixed histopathological and clinical features of IgAN and postinfectious glomerulonephritis. PMID- 1462007 TI - Normal renin-aldosterone-insulin and potassium interrelationship in FMF patients and amyloid nephropathy. AB - The renin-aldosterone system and plasma insulin were studied in 19 patients with familial Mediterranean fever (FMF). Their relationships to serum potassium level at rest and before and after oral glucose loading are described. An interesting finding is the occurrence of hyperkalemia in the absence of oliguria, in the advanced stages of renal failure. No differences were found in the activity of the renin-angiotensin-aldosterone system to explain these variations in serum potassium found in some of the patients. The response of the renin-aldosterone system to glucose loading showed no abnormality, and the regular relationship between serum potassium, plasma renin activity (PRA), aldosterone, insulin, and plasma pH is maintained. Levels of insulin, potassium, and bicarbonate in serum or plasma pH were found similar in FMF patients with normal renal function with and without proteinuria. Further decrease in renal function due to the progression of the underlying disease is manifested by an increase in FENa+ and FEK+ and a hyperchloremic metabolic acidosis, as is the case in other patients with chronic renal failure. PMID- 1462006 TI - Contrast media nephrotoxicity: comparison of diatrizoate, ioxaglate, and iohexol after intravenous and renal arterial administration. AB - In several studies in humans and animals it has been suggested that high osmolality and ionicity of contrast media are responsible for higher nephrotoxicity. To examine this suggestion, we evaluated the renal effects of three different contrast media--an ionic high osmolar, an ionic low osmolar, and a nonionic--following intravenous and renal arterial administration, in a population of 84 unselected, nondiabetic patients with adequate renal function. The results showed that the nephrotoxicity is minimal and equal for all three contrast media and for both routes of their administration, and it is concluded that in this category of patients the far higher cost of the newer low osmolar ionics and nonionics should be considered seriously in regard to nephrotoxicity. PMID- 1462008 TI - Interleukin-2 deficit in hemodialysis patients. Role of prostaglandins. AB - Uremic patients suffer from various immunological alterations, whose pathogenesis is still unknown. Here, we studied 37 hemodialysis patients in order to investigate the role of prostaglandins (PGs) in uremic immunological deficiency, specifically in relation to interleukin-2 (IL-2) synthesis. We confirmed previous published data on deficient response to PHA in chronic renal failure patients (cpm, mean +/- SEM: 15,400 +/- 2,100 in uremics vs. 29,500 +/- 3,380 in controls, p < 0.04) and established a correlation between this deficiency and diminished IL 2 synthesis (r = 0.619, p < 0.05). The direct measurement of PGs in lymphocyte cultures showed greatly increased concentrations in the presence of uremic serum (US). We found that PGs synthesis can be inhibited by up to 80% if cultures are supplemented with indomethacin (IND--a cyclooxigenase inhibitor) or by removal of monocytes (producers of PGs). Both methods situated the uremic proliferative response within the normal range in cultures with FCS, and close to the normal range in cultures with US. We observed a deficit of IL-2 in hemodialysis patients (means +/- SD: 8,940 +/- 6,420 in uremics vs. 16,900 +/- 3,890 in controls). Addition of exogenous IL-2 normalized lymphocyte response even in US cultures, with no additive effect between PGs inhibition and exogenous IL-2 except in US cultures. It is suggested that IL-2 deficit of uremics depends, at least in part, on an increase in PGs synthesis induced by US.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462009 TI - Performance characteristics of contemporary hemodialysis and venovenous hemofiltration in acute renal failure. AB - Modality choice in the treatment of acute renal failure (ARF) should be based on the match between individual patient needs and the characteristics of available therapies. Considerations include access, risk of bleeding, hemodynamic instability, and ability to remove excess volume. We prospectively studied 547 consecutive treatments for ARF in 110 patients to determine the performance features of modalities based on single-vessel venous access: hemodialysis (HD) and venovenous hemofiltration (VVH). All treatments were performed in an 18-month period at a single center. Patients' ages ranged from 16 to 84 years; 26 were trauma cases; 69 patients expired during their hospitalization. Mean number of treatments per patient was 4.97. Mean treatment duration was 197 min. Heparin was used unless active bleeding was present or felt to be a high risk; mean dose required was 2628 units. Pressor therapy was in progress prior to initiation of 260 (48%) of treatments. RESULTS: pretreatment and posttreatment mean systolic and diastolic BP were unchanged for the group. Forty-three (7.9%) treatments were terminated prematurely; of these only 27 (4.9%) were due to hypotension. No patient developed clinically apparent bleeding during any treatment. Contemporary equipment and techniques allow for provision of high-quality intermittent therapy for ARF, with excellent hemodynamic stability. Shorter, single-vein access treatments are advantageous for severely ill or injured patients who often undergo invasive monitoring and multiple studies or procedures. PMID- 1462010 TI - Influenza vaccination in chronic hemodialysis patients. The effect of zinc supplementation. AB - Since influenza increases the mortality of chronically ill patients we decided to study the effectiveness of influenza vaccination in hemodialysis (HD) patients. Nineteen HD patients aged from 20 to 60 years, on unrestricted diet and with no febrile episode, were studied. Blood samples were collected before the intramuscular injection of 0.5 mL multivalent influenza vaccine (Inflexal Berna) and every 2 weeks thereafter. At the end of 4th week a second vaccination was done and a dosage of 200 mg of zinc acetate (60 mg elemental zinc) was given daily to each patient for at least 4 weeks. Before vaccination the antibody titers to influenza virus ranged from 1:10 to 1:80 and after vaccination from 1:20 to 1:640. Four weeks after vaccination 6/19 (31.5%), 8/19 (42%), and 10/19 (52.5%) patients showed a fourfold or greater increase at serum antibody titers to antigens A/Singapore, A/Sichuan, and B/Beijing, respectively. The zinc supplementation after the second vaccination induced a similar increase of serum antibody titers to the A/Singapore but some even greater increase of the antibody titers to the A/Sichuan and B/Beijing. Serum immunoglobulins and complement components C3/C4 were not changed during this study. It is suggested that about 50% of uremic patients respond to the influenza vaccination and that zinc treatment does not increase this responsiveness. PMID- 1462011 TI - Evaluation and first validation study on a simplified drug dosage algorithm for multiple organ failure patients. AB - As reported previously, drug concentrations during continuous hemofiltration (HF) and extracorporeal lung assist (ELA) follow certain rules, which can be expressed by a simplified algorithm for dosage adjustment: Drug sieving (S, fu) depends on the protein free fraction with small limitations, while the extrarenal elimination rate is not a constant but correlates inversely with the clinical state, r = -0.34, p = 0.00067, n = 96. Up to now, more than 218 cases of drug dosage adjustments have been performed, following the described regimen: The expected concentration is obtained in 79-84% already from the first estimation for drugs such as aminoglycosides, vancomycin, teicoplanin, beta-lactam antibiotics, heart glycosides, and theophylline. Skilled therapeutic drug monitoring (TDM) with elaborated pharmacokinetic programs fails to improve these results significantly. Nevertheless, sporadic TDM is essential in these patients according to their rapidly changing clinical states. PMID- 1462012 TI - Bardet-Biedl syndrome and cystinuria. AB - An unusual association of Bardet-Biedl syndrome with cystinuria was described in one patient. A 21-year-old male was admitted to hospital because of renal failure, severe deterioration of visual acuity, polydactyly, brachydactyly, and mental retardation. Laboratory investigations revealed a serum creatinine of 292 mumol/L (3.3 mg/dL) and a GFR of 25 mL/min per 1.73 m2. Quantitative ion exchange chromatography demonstrated an increased urinary excretion rate of cystine, lysine, arginine, and ornithine. The ophthalmologic examination showed a severe atypical retinal dystrophy. Visual acuity was severely deteriorated and the patient could only count the examining physician's fingers. The patient had been previously evaluated at the age of 7 years for polyuria, polydipsia, and growth failure. His workup at that time demonstrated nephrogenic diabetes insipidus, normal GFR, and a urinary amino acid pattern consistent with the cystinuric phenotype. There was mental retardation notwithstanding the normal ophthalmologic examination. Intravenous pyelography showed calyceal clubbing, calyceal cysts, and lobulated renal outlines of the fetal type. The patient was evaluated again at the age of 13 years for deterioration of visual acuity and the ophthalmologic examination showed an atypical retinal dystrophy, with sparse pigmentation, central and peripheral atrophy, attenuated vessels, and marked optic disk pallor. To our knowledge the association of Bardet-Biedl syndrome with cystinuria has never been reported. It is unlikely that cystinuria may have contributed to the kidney damage. The possibility that mental retardation has been induced or aggravated by cystinuria cannot be excluded. PMID- 1462013 TI - Acute renal failure in severe hypothermia. AB - A patient who developed acute renal failure associated with severe hypothermia is reported. Warm peritoneal dialysis was initiated for core rewarming followed by intermittent hemodialysis till he entered the diuretic phase. The factors which led to acute renal failure in this patient included hypovolemia, hypotension, and acute pancreatitis. PMID- 1462014 TI - Thoracoscopy: the dawn of a new age! PMID- 1462015 TI - Anti-neutrophil cytoplasmic antibodies. PMID- 1462016 TI - Rationalising tuberculosis contact tracing in low prevalence areas. PMID- 1462017 TI - Cytokines, platelet activating factor and eosinophils in asthma. AB - Understanding of the pathogenesis of asthma has increased considerably during the past few years. These advances were possible through scientific progress in three areas which contribute to this complex and multifaceted disease: (a) the much clearer understanding of eosinophil function; (b) the defining of lipid mediators in tissue inflammation and bronchial obstruction; and (c) the growing knowledge about the biological action of a new class of protein hormones, collectively called cytokines. In line with this, evidence has accumulated of how these components may interact with each other in providing the basis of inflammatory processes in asthma. Hence it seems appropriate to review the potential implications of this new information for the pathogenesis and therapy of this disease. PMID- 1462018 TI - The determinants of the severity of acute airway narrowing in asthma and COPD. PMID- 1462019 TI - Radiological evidence of progression of bronchiectasis. AB - Radiological evidence of progression of bronchiectasis was sought in a group of 84 consecutive adult patients admitted to a tertiary unit with a particular interest in the disease. Methodical comparison for each patient of the earliest and most recent chest X-rays (n = 84), bronchograms (n = 1) and thoracic computed tomography (CT) scans (n = 32) was performed. Fifteen patients (18%) were considered to show radiological evidence of progression of bronchiectasis, 14 on chest X-ray, two of whom also showed progression on CT scans, and in one patient on bronchography alone. The likelihood of finding evidence of radiological progression increased the longer the interval between examinations. Serial radiology allows identification of patients with progression of disease and indicates the need to review management strategy. PMID- 1462020 TI - A high incidence of asthma and respiratory symptoms in 4-11 year old children. AB - A study assessing the prevalence of respiratory symptoms in two primary schools in Birmingham, U.K. was performed. A questionnaire was delivered to pupils in both schools after which three open days were conducted in one of the schools, where probable asthmatics were identified and referred to their General Practitioner, Chest Clinic or a school asthma clinic. In this school 49% of responders and 52.9% in the control school were symptomless on questionnaire: 31% and 20.8%, respectively, had probable asthma, falling to 20% and 15.5% if a positive response to the question on recent recurrent wheeze was disregarded as indicating asthma. Using the total population as a denominator, the overall asthma prevalence was 20% which is significantly higher compared to previous English rates. Forty-two were seen at the Chest Clinic, 14 being followed for more than two visits. None were on regular anti-asthma treatment initially; 12/14 were taking prophylactic treatment on follow-up. In the two schools, 10.0% and 14.2% of responders were 'chesty' with 'colds' having no other typical asthmatic symptoms: these children should be studied further. This high incidence of respiratory symptoms in primary school children could represent a national trend or just a local increase. PMID- 1462021 TI - Nebulized fenoterol causes greater cardiovascular and hypokalaemic effects than equivalent bronchodilator doses of salbutamol in asthmatics. AB - The pulmonary and extrapulmonary effects of two doses of nebulized fenoterol (5 mg) salbutamol (5 mg) and ipratropium bromide (0.5 mg) at 60 min intervals were compared in nine patients with asthma in a double-blind, randomized study. Measurements of heart rate, blood pressure, electromechanical systole (QS2I), QTc interval, FEV1 and plasma potassium were made at baseline and at 15, 30 and 60 min after each nebulization. Both beta-agonists caused significantly greater inotropic (QS2I), chronotropic (HR), electrocardiographic (QTc) and hypokalaemic effects than ipratropium bromide (IB), with fenoterol being more potent than salbutamol. Fenoterol had no greater effect on FEV1 than salbutamol although both were superior to IB. Only the first four subjects had two doses as originally intended, because the second administration of fenoterol resulted in marked cardiovascular effects and hypokalaemia. The observed differences in extrapulmonary effects between fenoterol and salbutamol provide a plausible group of mechanisms which may explain the increased risk of death associated with fenoterol in severe asthmatics. PMID- 1462022 TI - Chronic persistent cough: use of ipratropium bromide in undiagnosed cases following upper respiratory tract infection. AB - The clinical effects of inhaled ipratropium bromide were studied in 14 non smoking patients with persistent post-viral infective cough employing a controlled double-blind, cross-over trial. Patients were selected if they demonstrated no apparent underlying cause for their persistent cough after appropriate radiological and respiratory function tests including methacholine reactivity and bronchoscopic examination. Inhaled ipratropium bromide (320 micrograms day-1) produced significantly less day and night time cough (P < 0.05) with overall clinical improvement in 12 cases, five of whom had total resolution of their cough. We conclude that ipratropium bromide is an effective treatment in non-smoking adults with protracted cough following clinical upper respiratory tract infection. PMID- 1462023 TI - Pulmonary tuberculoma and indications for surgery: radiographic and clinicopathological analysis. AB - Tuberculomas of the lung are one of the more common lesions presenting a solitary pulmonary nodule, roentgenographically. We treated 36 patients with such nodules and describe here the radiologic-pathologic correlations and surgical treatment. In 21 patients, lung cancer was suspected preoperatively, based on radiographic findings of an ill-defined margin, pleural indentation and spicular radiation. Histologically, the tuberculous granuloma proliferated in the alveolar septa of the surrounding normal lung, often seen as a spicular radiation resembling lung cancer. In eight patients, tuberculoma was suspected because of radiographic findings of calcification and satellite nodules, and anti-tuberculous chemotherapy was prescribed for a few months. As this treatment was ineffective, surgical resection had to be done. Postoperative complications were nil and all of these patients are doing well at the time of preparation of this report. Anti tuberculous chemotherapy was prescribed for 28 of 36 patients, postoperatively. We believe that surgical intervention is required for selected patients. PMID- 1462024 TI - Pleural effusions: is thoracoscopy a reliable investigation? A retrospective review. AB - In this paper, we consider the results of thoracoscopy in a busy thoracic unit where the referring physicians place their greatest emphasis upon simple standard investigation of pleural disease. Between 1985 and 1989 620 patients with a pleural effusion of unknown aetiology were referred to our thoracic medical unit. Initial investigations included aspiration of pleural fluid for cytology and culture, and blind pleural biopsy for histological examination. Recourse to thoracoscopy was only taken in the absence of a diagnosis or non-resolution of the patients symptoms and signs. Of these 620 patients only 48 (8%) remained without a diagnosis and were referred for thoracoscopy. Histological assessment of biopsies obtained at thoracoscopy revealed malignancy in 24 patients (50%) and benign conditions in 16 patients (33%). In eight patients (17%) no conclusive diagnosis was established; in this latter group, six patients continued with their symptoms and further invasive investigations revealed malignancy. In this setting where thoracoscopy was used as a last resort, the sensitivity for thoracoscopy was 83% and the specificity was 100% with a predictive value of a negative result being 25%. In conclusion, from our experience, the majority of pleural disease may be diagnosed using simple techniques but thoracoscopy can be very helpful in the more complex cases. Moreover, inconclusive histology following thoracoscopy is an indication for further investigation if the condition does not improve. PMID- 1462025 TI - Time of development of tuberculosis in contacts. PMID- 1462026 TI - High velocity projectiles making contact with an unsuspecting pharyngeal wall. PMID- 1462027 TI - Simplifying the assessment of patients with chronic airflow limitation for home nebuliser therapy. PMID- 1462028 TI - [Epidemiology of malaria: research priorities (excluding entomology)]. PMID- 1462029 TI - [Coastal urban malaria in Cotonou (Republic of Benin). Entomological study]. AB - A one year entomological was carried out the survey in the coastal town of Cotonou to study the urban transmission of malaria. Three representative areas of Cotonou were chosen. The method adopted concerned night catches on human bait and dissection of A. gambiae s.l. The density of the vector (A. gambiae s.l.) fluctuated with the level of urbanization of the areas the annual aggressivity rates reached 1179 in the town center, 3666 in an the outskirts and 3363 in intermediate areas. Mean sporozoitic index was 1.7% and corresponding annual inoculation rate 46. In center of the town, transmission is seasonal and short, with a very high level. Sporozoitic index is 12% and the corresponding inoculation rate is 1.02. Outside of the town, transmission is seasonal and long: lasting 8 months. Transmission is imperceptible in the middle of the dry season and at the beginning of the long rain season. Malaria transmission into urban areas is generally low but in coastal like zones Cotonou, the intensity may be higher. PMID- 1462030 TI - [Morbidity and severity of malaria attacks in carriers of sickle-cell trait]. AB - The authors made a survey in a permanent high Plasmodium falciparum transmission area to compare frequency and severity of malaria attacks in children belonging to different haemoglobin types before 15 years; 291 young out-patients of the local infirmary and 467 outpatients of the hospital were examined. Diagnosis of malaria was inferred from clinical and parasitological criteria and subsequent evolution of the disease. Pathogenic threshold of parasitaemia was similar in all haemoglobin type groups of children and was about 3,000 parasite-infected red cells per mm3. Malaria was diagnosed more often among HbAA patients, than among other patients. Mortality rate in AA haemoglobin children was higher than 3% whereas in sickle cell trait carriers no death could be certainly attributed to malaria. The S gene rate was significantly weaker (p < 0.05) in subjects attacked by Malaria (5%) than in all other groups of children. In the endemic malaria areas the susceptibility of S gene carriers appears to be lesser than in AA haemoglobin children and could explain the paradoxically lower rate of mortality in this group. PMID- 1462031 TI - [Plasmodium falciparum or P. malariae parasitemia in carriers of sickle cell trait in various Benin biotypes]. AB - The prevalence of malaria and the frequency of gene S were surveyed in two different regions of Benin, savana and coastal lacustrine regions. In both regions, prevalence of malaria was not significantly different between Hb AA people and Hb AS people. Gene S prevalence was not modified by age, excepted for Hb SS which was not found in people upper than 25 years. In holoendemic area, i.e. lacustrine region, means of P. falciparum parasitaemia were significantly lower in Hb AS children than in Hb AA children. Sickle cell trait did not reduce the prevalence of malaria but seemed to decrease the level of parasitaemia. PMID- 1462032 TI - [Urbanization and nutritional transition in sub-saharan Africa: exemplified by Congo and Senegal]. AB - To evaluate the impact of urban life-style on nutritional status, body mass index (BMI) of mothers and indices of malnutrition of preschool children were calculated in four representative surveys in two rural areas and two main cities of Western and Central Africa. Mean BMIs were similar in both urban settings and were significantly higher than those of rural mothers. Distributions shifted significantly towards values over 25 kgs/m2 in towns, although, values lower than 18.5 were still present. Therefore chronic energy deficiency, largely prevalent in many rural areas of Africa, remains important in cities, where obesity also appears to have become a public health concern. Wasting was rare in young urban children, but the prevalence of stunting, although lower, indicates the persistence of nutritional deficiencies. This situation of nutritional transition generates a double burden to already limited health finances and requires an appropriate educational policy. PMID- 1462033 TI - [Anemia at delivery in Lome (Togo): prevalence, risk factors and consequences in newborn infants]. AB - A prevalence study was carried out on 125 mothers and their newborns in Lome (Togo): at delivery 48% of the mothers and 30% of the newborns were anaemic according to WHO criteria. Iron deficiency was the major determinant of anaemia in the mothers, as three out of four showed at least one biochemical indicator of iron deficiency. Folate deficiency was detected in 68% of the mothers but did not influence their haematological parameters. Severe iron deficiency in the mothers (serum iron < 7 mumol/l) was associated with a decrease in serum iron in the newborns, thus demonstrating an impaired iron transfer to the fetus. Folate supplementation of the mothers during pregnancy improved their newborn's folate status. A systematic ferro-folic supplementation is needed during pregnancy and would be beneficial to both mothers and newborns. Supplements could be given to women at prenatal care clinics. Attendance in these centers by 98% of pregnant women in Lome allows us to anticipate a good coverage for such an intervention. PMID- 1462034 TI - [Man-water contacts and urinary schistosomiasis in a Mauritanian village]. AB - For the period September to December 1985, 1226 water contacts were recorded during 8 days of direct observation. Various activities were analysed in order to determine their responsibility in transmission. An index of exposure, allowing for duration of contact, body surface exposed and infectiousness of the water was calculated for each contact. Domestic contacts, primarily female, represented 62% of the observations but only 15% of total exposure. Conversely, contacts for recreational purposes mainly involved young boys and accounted for 14% of the observations and 70% of total exposure. Between 6 and 20 years of age the mean index of exposure by contact was higher in males than in females. Changing water contact behavior seems to be an unrealistic means of preventing transmission in the community studied. The most appropriate strategy of control would appear to be selective treatment of heavily infected individuals. PMID- 1462035 TI - [STATCAN:a telemetric information system of mortality and incidence of cancer in France]. PMID- 1462036 TI - [Polyneuropathies associated with lymphoplasmacytic dyscrasias: the clinical and instrumental characteristics of a 38-patient case load]. AB - A varying percentage from 40 to 60% of patients having lymphoplasmacytic dyscrasias with a monoclonal component shows a clinical or subclinical polyneuropathy. From a different viewpoint, a monoclonal gammopathy has been detected in 10% of patients effected by chronic idiopathic polyneuropathy. A case study of 38 patients with lymphoplasmacytic dyscrasia subjected to clinical, immunohematological and electrophysiological examination revealed a high prevalence of polyneuropathy (84%), mainly axonal (72%) and often subclinical. The neuropathy was evenly distributed between patients having malignant and benign lymphoplasmacytic dyscrasias. No statistically significant correlation was found between the presence of neuropathy and the main clinical and immunohematological data. This supports the concept that the pathogenesis of polyneuropathy associated with lymphoplasmacytic dyscrasias may be multifactorial. Nor can it be ruled out that the paraprotein may in fact be secondary to the polyneuropathy or sometimes a simple coincidence. PMID- 1462037 TI - [The soluble IL-2 receptor in malignant hemopathies]. AB - The increase in the serum levels of the IL-2 receptors is due to its release both in vivo and in vitro from activated cells or neoplastic cells expressing it constitutively. The diagnostic, prognostic and physiopathologic significance of the sIL-2R was investigated by testing the serum of 271 haemopathic patients in various stages of the disease. In HCL the elevated sIL-2R level has a diagnostic value. In HD the sIL-2R level appears to be directly correlated with the extent of the disease and is equally important in the follow up of patients with HCL, NHL, HD, AL and MDS, where the serum level of the soluble receptor is usually associated with the biological and clinical activity of the disease. Unlike other B lymphoproliferations, patients with Multiple Myeloma on average show only slightly elevated levels of soluble receptor with no significant differences related to the stage or evolution. As for the chronic myeloproliferative disorders, we found only slightly elevated values in ET and PV, with frankly pathological values in CML during a blastic crisis or in the accelerated phase and in MFI during the clinically active phase of the disease. PMID- 1462038 TI - [Ebstein's tricuspid anomaly and Down's syndrome. A clinical case report]. AB - The authors describe a case of a 55 years old white man with Down's syndrome in whom an Ebstein's anomaly of tricuspid valve was casually diagnosed. The peculiarity of this association was searched in the literature, trying to explain, at the same time, the poor symptomatology. The role of echocardiography in the diagnosis of Ebstein's anomaly is emphasized. PMID- 1462040 TI - [Totally implantable systems for long-term chemotherapeutic treatment]. AB - The authors report their own experience with completely implantable systems for the long-term chemotherapeutic treatment, compared with a review of modern literature. The experience even if low demonstrates a good methodology in reducing the number of complications associated with the use of percutaneous catheters. PMID- 1462039 TI - [Horton's bitemporal arteritis. A case report]. AB - The authors report a case of Horton's arteritis in a woman (aged 76) presented some peculiarities. The arteritis simultaneously interested both superficial temporal arteries; in a second time caused a bilateral "claudicatio masticationis"; induced a worsening of extrapyramidal symptoms from which the patient had been suffering for many years, due to the possible involvement also of the endocranial arteries. The histologic picture on a biopsy of the left temporal artery was typical of the Horton's disease, but without giant cells; the authors suppose that this is due to a therapy with FANS administered before carrying out the biopsy. The patient was treated with cortisone per os at a low dosage, causing a quick regression of the symptoms and a normalization of the laboratory tests. Also this result differs from what most authors have observed: they maintain that Horton's arteritis has become rather resistant to the cortisone therapy and required high dosage for a very long time. The authors maintain that precocity of diagnosis and an immediate treatment can influence in a significant way the course of the disease. PMID- 1462041 TI - [Recent findings on the pathogenesis and therapy of anemia in chronic kidney failure]. AB - Recent studies showed that the blood BFU-E, when subtracted from the uremic milieu, normally responds to the stimulating factor produced by T lymphocytes. The serum of uremic patients inhibits the in vitro growth of normal BFU-E, however, the inhibition is almost completely reversed by hemodialysis. These data allow to understand why the therapy with erythropoietin relieves the anemia of CRF. Uremic T lymphocytes fail to stimulate the BFU-E growth. Normal T lymphocytes are inhibited by uremic serum and the hemodialysis does not correct the defect. Lymphopenia, decreased number of both T4 and T8 lymphocytes and low T4/T8 ratio were found in 50% of patients. Cimetidine was still able to increase the burst-stimulating activity of uremic T lymphocytes through inhibition of the suppressor T subset. In conclusion, one can say that in CRF T8 lymphocytes are normal and that uremic toxins decrease both number and function of T4 lymphocytes. The deficiency of BPA appears to significantly contribute to the pathogenesis of the anemia of CRF. The experience from our and other Institutions shows the effectiveness of the recombinant human erythropoietin in relieving the anemia of CRF, notwithstanding the hematological milieu is highly modified by uremia. PMID- 1462042 TI - [Glanzmann's thrombasthenia: a rare example of an integrin deficit]. AB - Glanzmann's thrombasthenia is an autosomal recessive life-long bleeding disorder, originated from a quantitative or qualitative defect of the major platelet membrane receptor: the GPIIb/IIIa complex. The GPIIb/IIIa complex is a calcium dependent heterodimer, belonging to the integrin superfamily. The complex of activated platelets can bind fibrinogen, von Willebrand factor, fibronectin and vitronectin, which are proteins playing an important role in platelet adhesion and aggregation. Thrombasthenic platelets are deficient in GPIIb, GPIIIa and GPIIb/IIIa complex; however, platelets from few thrombasthenic patients content near-normal amounts of functionally abnormal complex. The GPIIb/IIIa quantitative or functional defect leads to defective platelet hemostatic plug formation. Hemorrhagic symptoms consist of purpura, gingival hemorrhage, menorrhagia and epistaxis. Some cases of Glanzmann's thrombasthenia have been characterized at the molecular genetic level. Molecular abnormalities include: GPIIb or GPIIIa partial gene deletion, GPIIIa gene insertion, a point mutation resulting in an amino acid substitution within the GPIIIa molecule. In spite of the contemporary reduction of both GPIIb and GPIIIa in most cases of Glanzmann's thrombasthenia, it appears that a molecular abnormality affecting only one of the glycoprotein genes may result in a thrombasthenic phenotype. PMID- 1462043 TI - [The endothelial cell: a cell structurally simple but functionally very complex]. AB - Vascular endothelium is morphologically similar to a simple squamous epithelium that lines the internal surface of vessels. These cells, even if structurally simple, are functionally very complex. They regulate vascular tone by producing vasodilators such as prostacyclin and nitric oxide and vasoconstrictors such as endothelin. In addition, endothelial cells express activators and inhibitors of coagulation, fibrinolysis and platelet aggregation. Alterations of the functional equilibrium of endothelial cells might be related to the development of many cardiovascular diseases. PMID- 1462044 TI - Exposure to ozone and erythrocyte osmotic resistance in the rat. AB - In order to learn the biological effect of photochemical oxidants on living bodies, we exposed newborn and adult rats, of both sexes, to ozone at a concentration of 0.25 ppm, which can be encountered in an urban environment, and then measured the osmotic resistance of their erythrocytes. The results of experiments using newborn rats indicated a positive increase in the osmotic resistance of erythrocytes in whole blood following ozone exposure for 4 weeks. An increase in the osmotic resistance of erythrocytes in the top part obtained by centrifugation was observed following ozone exposure for 12 weeks. This tendency was especially evident among male rats. On the other hand, no increase in the osmotic resistance of erythrocytes was recognized in the adult animals which had been exposed to the same concentration of ozone for 18 months. PMID- 1462045 TI - In vivo glycogen and lipid synthesis by various tissues from normal and metformin treated KK mice. AB - The incorporation of [14C] U-glucose into glycogen by liver, kidney and skeletal muscle and that into total lipid by adipose tissue was studied in noninsulin dependent genetically diabetic KK mice treated either with metformin (50 mg/kg) or water for 10 weeks. Results show that glycogen synthesis was increased in the skeletal muscle from metformin-treated mice. Liver and kidney glycogen synthesis was not affected by metformin. Glucose incorporation was significantly increased into lipid in metformin-treated mice. Insulin administration stimulated lipid synthesis in adipose tissue, but had no effect on muscle glycogen synthesis in metformin-treated mice. These data suggest that chronic metformin treatment potentiates the endogenous insulin action on glucose in skeletal muscle and adipose tissue, and thus confirm our previous results of increased glycogen synthesis by skeletal muscle in metformin-treated KK mice. PMID- 1462046 TI - Pseudocholinesterase in alloxan-diabetic rats. AB - Pseudocholinesterase (PChE) activity in plasma, liver, pancreas and adipose tissue of alloxan-diabetic rats has been determined. 48 hours after the induction of diabetes an increase of PChE activity in plasma and a decrease in liver and adipose tissue was observed. After that, the activity in plasma remained at the same level, in the liver it slowly rose to the control values and in adipose tissue significantly increased beyond the control values. Significant changes of PChE activity in the pancreas were not noticed. Female rats had higher PChE activity in plasma and liver than the male, but in the pancreas and adipose tissue there were no sex differences. On the basis of our results it seems possible to propose that PChE is synthesized also in adipose tissue, but the synthesis is regulated by different mechanisms than those in the liver. PMID- 1462047 TI - Synergism of cyclosporin A and phospholipase inhibitors in protection against lethal injury to rat hepatocytes from oxidant chemicals. AB - Cyclosporin A and phospholipase inhibitors block the oxidant-induced mitochondrial permeability transition. Here, protection by these agents against cytotoxicity of oxidant chemicals was evaluated in rat hepatocytes. The combination of cyclosporin A and a phospholipase inhibitor (trifluoperazine, mepacrine, or dibucaine), but neither alone, substantially protected against lethal injury from 0.5 mM iodoacetate but had little effect against iodoacetate plus 2.5 mM KCN. Against 100 microM t-butylhydroperoxide, cyclosporin A and trifluoperazine protected only if fructose was present. Cyclosporin A plus phospholipase inhibition protected slightly against 2.5 mM cystamine, but actually increased lethal injury after 100 microM menadione. These effects are consistent with an oxidant-induced mitochondrial permeability transition that accelerates cell killing after iodoacetate and t-butylhydroperoxide. PMID- 1462048 TI - Membrane-associated phospholipase A2 stimulates DNA synthesis in two murine fibroblasts. AB - The effect of human membrane-associated phospholipase A2 (M-PLA2) on DNA synthesis in fibroblasts was examined in order to clarify its biological function. Human M-PLA2 added exogenously to the fibroblast cell lines Swiss 3T3 and BALB/3T3 was found to augment their DNA synthesis. This stimulation of DNA synthesis was not affected by treatment with indomethacin. Our results suggest that human M-PLA2 itself has a mitogenic effect on fibroblasts independent of arachidonate products such as prostaglandins. PMID- 1462049 TI - Cardiovascular actions of NG-methyl-L-arginine are abolished in a canine shock model using high-dose endotoxin. AB - This study was designed to test the hypothesis that endotoxin-induced hypotension is caused, in part, by increased endothelial synthesis of nitric oxide and that inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (NMA) would reverse the cardiovascular actions of endotoxin. A high dose of endotoxin (1.5 mg/kg, i.v.) was administered by rapid intravenous infusion to pentobarbital anesthetized dogs. Endotoxin caused rapid and profound reductions in cardiac output and mean arterial pressure; systemic vascular resistance, however, was unaltered except for a transient increase. Coronary and mesenteric blood flows were reduced. NMA (30 mg/kg, i.v.) given 60 min after endotoxin administration, had no significant effect on cardiac function or systemic vascular function except for a transient increase in cardiac output and decrease in systemic vascular resistance. This same dose of NMA given to dogs not receiving endotoxin caused systemic vasoconstriction, increased arterial pressure and decreased cardiac output. These results suggest that increased nitric oxide production is not a primary factor causing endotoxin-induced hypotension and that nitric oxide does not modulate vascular tone following administration of high doses of endotoxin. PMID- 1462050 TI - The "anesthetic" effect of alcohols and alkanes in Caenorhabditis elegans (C.e.). AB - In order to help validate the free-living roundworm, C.e., as a simple model to study the mechanism of general anesthesia, we demonstrated that homologous series of alcohols and alkanes produced a reversible "anesthetic" effect in these worms as in other animals. Also, as in other animals, the potency of these compounds was directly related to their respective lipid solubilities within each series. The alcohols were much more potent than the alkanes even though the latter were much more lipid soluble than the alcohols. The cut-off point (a decrease followed by a loss of activity) for these compounds occurred at about C9. In mice, the alcohols had an effect analogous to that seen in C.e. but the alkanes were inactive after intraperitoneal injection. PMID- 1462051 TI - Oxidative metabolism of flunarizine in rat liver microsomes. AB - The oxidative metabolism of flunarizine [1-[bis(4-fluorophenyl)-methyl]-4-(3 phenyl-2-propenyl)piperazine, FZ] to 1-[bis-(4-fluorophenyl)methyl]piperazine (M 1), 1-[bis(4-fluorophenyl)methyl]-4-[3-(4'-hydroxyphenyl)-2- propenyl]piperazine (M-2) and 4,4'-difluorobenzophenone (M-3) has been studied in liver microsomes of Wistar and Dark Agouti (DA) rats. Kinetic analysis demonstrated a sex difference (male > female) in the formation of M-1 and M-3, but not in that of M-2 in Wistar rats. Comparison of the kinetic data of FZ with those of cinnarizine [1 (diphenylmethyl)-4-(3-phenyl-2-propenyl)piperazine, CZ], a prototypic and unfluorinated drug (Kariya et al., Biochem. Pharmacol., in press) revealed that the formation clearances (Clfs) estimated by Vmax/km for the ring hydroxylated metabolites of FZ and CZ are higher than those for the N-dealkylated metabolites of these drugs in female rats. Furthermore, the introduction of two fluorine atoms to CZ (forming FZ) decreased the Clfs for most of metabolites, especially for the N-dealkylated product, M-3. The formation of the metabolites from FZ was suppressed by carbon monoxide and SKF 525-A, and only the ring hydroxylation forming M-2 was significantly lower in female DA than in female Wistar rats. These results suggest that the microsomal oxidation of FZ is mediated by cytochrome P450, and that a cytochrome P450 isozyme(s) belonging to the CYP2D subfamily is involved in the ring hydroxylation of FZ forming M-2. PMID- 1462052 TI - A simplified gelatin tolerance test to evaluate gastric and pancreatic proteolytic activities. AB - To evaluate gastric, pancreatic and intestinal proteolytic activities, a gelatin tolerance test was standardized, and its clinical significance was evaluated in 16 normal subjects and 25 patients who had undergone gastrectomy or had a pancreatic disease. A 15g gelatin dose given to normal subjects resulted in an increase of serum-free and peptide-bound hydroxyproline (HYP), with the peak values being observed at 1 hr and 2 hr, respectively. In patients who had malabsorption, both peak levels of serum-free and peptide-bound HYP were decreased, and the peak value of free HYP was more frequently lower than that of peptide-bound HYP. The determination of serum free HYP after oral administration og gelatin was significantly correlated with BT-PABA test. These results indicate that usefulness of determining serum-free HYP for the gelatin tolerance test as a simple reliable test for digestion and absorption of proteins. PMID- 1462053 TI - Reimbursement of biotherapy: present status, future directions--perspectives of the third-party payer. AB - The mission of insurers is to provide defined financial support for health care therapies deemed appropriate for use in specific clinical situations. In the current health care financial crisis, insurers are faced with keeping costs to a minimum and premiums reasonable. While insurers wish to finance the best available treatment, it is not always fiscally responsible or realistic to fund care provided in investigational therapies. The Blue Cross and Blue Shield Association (BCBSA), as the national coordinating body for local Blue Cross and Blue Shield Plans, assesses the status of new technologies, such as the biotherapy of cancer, through its Technology Evaluation and Coverage (TEC) Program and its Medical Necessity Program. Fundamental to both programs is whether a technology is effective: Does it improve health outcomes? And, if it does, what are its appropriate conditions of use? New technologies demonstrated by clinical research to improve health outcomes and found consistent with other related criteria are considered eligible for coverage by the TEC Program. New technologies not yet established as effective by clinical research and approved through the TEC Program are considered investigational. Most Blue Cross and Blue Shield Plan contracts exclude coverage for such investigational technologies. Most plan contracts also have medical necessity clauses, whereby only medically necessary technology uses are covered. Central to this is clinical research on appropriate medical conditions of use--the focus of the Medical Necessity Program. Valid conclusions on whether a technology works and where and when it works the best presuppose well-designed scientific studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462054 TI - Patterns of self-care needs and interventions related to biologic response modifier therapy: fatigue as a model. AB - Many patients receiving biologic response modifier (BRM) therapy experience fatigue as a significant and, at times, dose-limiting side effect. For this reason, a multiinstitutional pilot study was designed to collect data about the needs and self-care interventions of patients who had undergone at least one prior treatment with a BRM and had experienced fatigue as a symptom. Information was also obtained on the extent to which the needs and self-care interventions identified by patients compared with those perceived by their family members and nurses. Of the 16 patients who participated in the study, seven were being treated with interleukin-2 (IL-2), eight with interferon alfa (IFN-alpha), and one with tumor necrosis factor (TNF). The study found no significant correlation between the degree or duration of fatigue and the BRM or dosage administered. Not surprisingly, patient and family member responses correlated fairly well. However, in several parameters, including the degree and duration of fatigue, nurses' perceptions did not correlate at all with those of the patient. While 46% of nurse responses matched those of the patient as to useful self-care interventions, only 17% of nurses accurately identified factors or events that patients perceived as worsening fatigue. Further, there was no correlation among patient, family member, and nurse responses on interventions that could be used by others to help the patient cope with fatigue. The overall results of this pilot study indicate that nurses need to be more attuned to assessing fatigue as a side effect of BRM therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462055 TI - Symptom assessment and management of outpatients receiving biotherapy: the application of a symptom report form. AB - Patients treated with high doses of biologic response modifiers (BRMs) often require hospitalization for monitoring and management of toxicities. However, with careful symptom assessment and management, patients can be treated safely with low-dose, long-term BRM regimens in an outpatient setting. Quantifiable, consistent, and accurate symptom assessment sets the groundwork for regular, effective symptom management. A symptom report form or nursing care flow sheet is a helpful daily assessment tool for recording and quantifying the most common side effects experienced by patients receiving BRMs. Parameters can be established and converted to a numerical code to provide a consistent guide for evaluating a patient's toxicities during treatment. Additional space on the report form allows for narrative comments about symptoms or concerns not addressed elsewhere. To be safe and effective, outpatient therapy of this kind requires excellent patient education and compliance, with easy access to a health care professional when necessary. PMID- 1462056 TI - Reimbursement of biotherapy: present status, future directions--perspectives of the hospital-based oncology nurse. AB - Cancer is a set of diseases that affects one in four Americans and which is too often fatal. For many types of cancer, there is no fully satisfactory treatment. Therefore, investigational therapy provided in a formal, peer-reviewed clinical trial can present the best available treatment for patients with life-threatening malignancies. At a time when clinical cancer research is at a particularly promising point and multiple new biologics are on the horizon, the traditional partnership of the federal government, the pharmaceutical industry, private institutions, and insurers is threatened. The issue of increasing concern is the impact of changes in third-party reimbursement policy on cancer clinical investigation. Although its incidence, magnitude, and geographic distribution have not been specifically defined, this issue is generating serious concern and intense national debate. The growing denials of patient-care costs related to clinical trials serve to threaten patient access to potentially efficacious therapy. The implications of this reimbursement issue are tremendous for both clinical investigation and patient care. The refusal to pay for patient-care costs related to investigational therapy may adversely influence clinical trial design and will certainly affect the speed with which new therapies are developed. When insurers refuse to cover these clinical costs, only affluent individuals have access to the most promising treatments. Nursing actions can positively affect the reimbursement debate. Nurses must develop cost-efficient plans of care and the means to evaluate their effectiveness. Educating patients about and assisting them with reimbursement issues maximizes their prospects for receiving appropriate investigational therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462057 TI - Reimbursement of biotherapy: present status, future directions--perspectives of the office-based oncology nurse. AB - Economic forces are stimulating cost sensitivity and the need for clinical efficiency in medicine. The federal government has led the way with Medicare reform, and cost-containment efforts are evident in all health care payer programs. More and more, the office-based oncology nurse is involved in reimbursement issues as both a colleague and a patient advocate. Creative solutions to the challenges of reimbursement require knowledge of the issues, familiarity with patient-specific therapies, and recognition of unique cost and billing issues. Biologic agents frequently used in office-based oncology practice are easy targets for reimbursement denials because of regulations against their investigational status, "off-label" use, method of administration, and relatively high cost. Such agents include interferon, erythropoietin (EPO), granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF, respectively), and interleukin-2 (IL-2). Reimbursement decisions are often characterized by inconsistency and uncertainty, and rulings are based not only on law, but also on interpretation. The need for clarification often opens a window for negotiation for the complex reimbursement issues associated with biotherapy. In addition to thoroughly determining cost and accurately assigning appropriate Current Procedural Terminology (CPT) codes, office-based oncology nurses can pursue various strategies to help their patients and practices obtain reimbursement of biotherapy. Chief among these is educating third-party payers on the appropriateness and necessity of newer treatment modalities. In individual cases, documentation of the scientific data, clinical outcomes, and cost benefits supporting a treatment decision almost always gains reimbursement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462058 TI - [Pulmonary embolism: which diagnostic approach?]. AB - The recent literature dealing with the diagnosis of pulmonary embolism is reviewed. Clinical signs, electrocardiogram and arterial blood gases analysis are not very helpful whereas a normal level of blood D-dimers makes the diagnosis of pulmonary embolism very unlikely. Lung scanning must be interpreted carefully in parallel with chest radiography. It is most useful if the pattern is either normal or of high probability. All intermediate scans are inconclusive and need a pulmonary arteriogram. Another option in patients with good cardiorespiratory reserve is the use of repeated non-invasive investigations of the lower limbs. PMID- 1462059 TI - [Creation of a planned autologous transfusion unit in a hospital distinct from a transfusion center]. AB - Autologous blood predonation now widely used for programmed surgery has been recently regulated by a law from january 9 1992. It establishes that the procedure must be performed under the responsibility of an accredited blood transfusion center. This work discloses that the establishment of an autotransfusion unit in a hospital endowed with an active surgical program is feasible, the major objective being improvement of the quality of life of elderly patients with invalidating diseases. We report the one year experience of a collaboration between the Braine-l'Alleud-Waterloo hospital and the Red Cross Erasme-Brabant Wallon blood transfusion center. Eighty patients enrolled in programmed surgery consisting mostly in orthopedic surgery have given 187 units of packed red blood cells and fresh frozen plasma. Sixty two patients (83%) were transfused solely with autologous blood. Tolerance was excellent as only 4 slight malaise episodes were observed. Our study also indicates that programmed predonation should be proposed mainly to patients for whom the prescribed blood is effectively transfused. Creation of such autotransfusion units in hospitals distinct from a blood transfusion center is feasible with the deep collaboration between physicians in charge of the patients, the hospital laboratory and the blood transfusion center. PMID- 1462061 TI - [Deafness and vertigo. Otospongiosis of the cochlea and auditory plate]. PMID- 1462060 TI - [Persistent and recurrent hyperparathyroidism following parathyroidectomy]. AB - In a series of 416 parathyroidectomies for primary or secondary hyperparathyroidism, 19 were reoperations for persistence (17 cases) on recurrence (2 cases) of the disease. (1) Preoperative localisation studies were useless in half of the cases. (2) In re-explorations, 72% only of parathyroid glands were discovered, 46% of them in ectopic locations. In reoperations for primary hyperparathyroidism, 56% of cases had more than one pathological gland. (3) Long term results have been less satisfactory after re-explorations than after the first operations. PMID- 1462062 TI - [Diffuse pulmonary hemorrhagic diseases: clinical and diagnostic approach]. PMID- 1462063 TI - [Adaptation of the cardio-respiratory system of the elderly during physical training]. PMID- 1462064 TI - [Therapeutic alternatives in Crohn disease and in ulcero-hemorrhagic rectocolitis: current findings]. PMID- 1462065 TI - [Left cor triatriatum. Literature review. Apropos of a case report]. PMID- 1462066 TI - [Diffuse nodular or regenerative hyperplasia of the liver responsible for portal hypertension. Apropos of a case and literature review]. PMID- 1462067 TI - [What is your diagnosis? Acute intermittent porphyria]. PMID- 1462068 TI - [Current aspects of neurosyphilis: therapy-resistant cases with high-dosage penicillin?]. AB - The occurrence of atypical and abortive cases of neurosyphilis in the last two decades has tended to make this rather infrequent, treatable condition difficult to diagnose; therefore it is advisable to perform large-scale serologic tests among neurologic and psychiatric patients. The diagnosis is confirmed by the detection of treponema antibodies in the central nervous system (TPHA index, ITpA index). When serologic test results are positive, secondary diagnostic criteria are provided by pathologic CSF findings (elevated cell count, humoral immune reaction). The course of the disease and the CSF parameters are favourably influenced by appropriate therapy. Over the last two decades, there has been an increase in the number of reports of cases refractory to the low-dose penicillin treatment recommended by the WHO and the CDC until two years ago. There have also been reports of treponema resistance in association with this therapeutic strategy and furthermore of failure to detect CSF concentrations of penicillin capable of eradicating the spirochetes. Counter measures have been taken worldwide in the last few years in the form of high-dose penicillin therapy (approx. 20 million IU/day for 2 to 3 weeks), in the hope that this would eliminate the resistance. We observed two patients treated with 18 and 24 million IU penicillin for 10 and 14 days respectively. The pathogens remained resistant, and the disease continued to progress. In one of these cases, immunologic processes might have been predominantly responsible for the resistance to the treatment, while in the other resistant pathogens can be assumed to be responsible. Repeated courses of treatment with higher doses of penicillin and/or with ceftriaxone finally succeeded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462069 TI - [Localization of level of lesions in internuclear ophthalmoplegia through assessment of masseter and blink reflex]. AB - The masseter and blink reflexes were investigated in 100 patients with internuclear ophthalmoplegia due to multiple sclerosis (58 patients) or lacunar brainstem infarction (42 patients). In unilateral internuclear ophthalmoplegia, 38 of 60 patients (63.3%) had masseter reflex abnormalities, two patients (3.3%) showed changes of the blink reflex R1 component, and 13 patients (21.7%) combined alterations of the masseter reflex and the blink reflex R1 component. 46 (86.8%) of these 53 patients with electrophysiological abnormalities had unilateral changes, which were ipsilateral to the medial longitudinal fasciculus lesion in 42 patients (91.3%). In bilateral internuclear ophthalmoplegia, 24 of 40 patients (60.0%) had abnormalities of the masseter reflex, two (5.0%) showed changes of the blink reflex R1, and nine (22.5%) combined alterations of the masseter reflex and the blink reflex R1 component. 20 (57.1%) of these 35 patients with electrophysiological abnormalities had bilateral changes. Thus, masseter reflex abnormalities indicating midbrain lesions were seen in 63.3% and 60.0%, respectively, of unilateral and bilateral internuclear ophthalmoplegia. Blink reflex R1 component changes with or without impairment of the masseter reflex indicating rostral pontine to midpontine lesions occurred in 25.0% and 27.5%, respectively. These figures correspond to the results of postmortem examinations and to theoretical considerations based on the length of the medial longitudinal fasciculus. PMID- 1462070 TI - [Romantic origins of electrophysiology]. AB - Research on static electricity and its effects on the human body date back to the invention of the electrizing or Wimshurst machine and the Leyden jar of 1743 and 1746. Such experiments often served as social pastimes, but they yielded many publications on medical aspects of static electricity. Attempts to explain the 'life force' of the vitalists and the old concept of the active principle of the nervous system, the 'spiritus animales', as electrical phenomena were unsuccessful because of the skeptic comments of leading experimental scientists such as Albrecht von Haller. When Mesmer reinvented 'animal magnetism' in 1776 as a fashionable term for treatment by suggestion, he appropriated theoretical, technical and social methods from the established ways of the experiments on static electricity. Therefore, the scientific character of Luigi Galvani's investigations was already compromised by his term 'animal electricity' when he published his famous 'Commentarius' in 1781. Volta in Pavia turned against Galvani, proving that galvanic currents are produced by metals alone, and rejecting 'animal electricity'. Volta's doctrine prevailed over Galvani's school after Volta's breakthrough with his pile, or battery, until Galvani's ideas were rehabilitated by Nobili, who in 1828 measured the 'frog current' with his galvanometer. This led to a flurry of bizarre experiments on rows of half dismembered animals and severed parts of human cadavers. Johannes Muller in Berlin, who, with his students, established new principles of biology and neurology, asked Du Bois-Reymond to study these experiments. Du Bois-Reymond found that measurements of muscle currents in intact animals were more useful, and he compared them with his own observations on electric fishes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462071 TI - [Motor evoked potentials. Physiology, indications, safety aspects]. AB - The motor cortex and the proximal part of the peripheral nervous system can be stimulated by a rapidly changing magnetic field. The procedure is simple, painless and safe. It allows to quantify the function of the most rapidly conducting corticospinal fibers. It is possible to detect subclinical lesions. The use of this technique for the study of lesions of the proximal parts of the peripheral nervous system is as of yet largely experimental. PMID- 1462072 TI - [Gait analysis--a prerequisite for general movement analysis]. AB - Our system for analysis of gait is a combined visualisation of angular velocities in any joint with dynamic measurements of pressure at the sole while walking in a natural surrounding. Infrared reflectors are attached to chosen parts of the body. Their position in space is sampled over time and transferred to an easily manageable personal computer that visualizes motion in progression as angular velocities. Pressure at the sole is measured by pressure sensors. The magnitude of force is expressed as calibrated circular areas following the dynamic course of gait. The system is accurate and easily operated. The time necessary for measurements and evaluation of data as well as the costs render an application in daily clinical work acceptable. PMID- 1462073 TI - [Epilepsy in middle and older age]. AB - Single fits and epileptic illness are more frequent in advanced age; their occurrence reaches the same frequency as in the neonatal period. Their origin and the possibilities of treatment are tightly connected to the process of ageing, a fact that requires special consideration. The main reasons for new epileptic attacks in the group of age 65 or more are structural changes, i.e. ischemic infarctions, tumors and atrophic involution. For certain patients, the use of antiepileptic drugs may be limited by unavoidable side effects. Complete cure of the attacks in advanced age is rare, but with a well selected treatment sufficient control is often possible. PMID- 1462074 TI - [The practitioner facing the patient with chronic pain or how to preserve the free spirit in a relational impasse]. PMID- 1462075 TI - [Traumatology of the shoulder]. PMID- 1462076 TI - [History of medicine--what relevance and which common boundaries today?]. PMID- 1462077 TI - [A true ambulatory service]. PMID- 1462078 TI - [Physiopathology of obesity]. PMID- 1462079 TI - [Epidemiology of obesity]. PMID- 1462080 TI - [Food diaries in the follow-up of obese patients]. PMID- 1462081 TI - [Obesity: from anamnesis to choice of treatment]. PMID- 1462082 TI - [Follow-up of patients after gastroplasty]. PMID- 1462083 TI - [Role of psychiatry in a multi-disciplinary practice for patients with excess weight]. PMID- 1462084 TI - [Weight loss in obese patients. Importance of assessment of body composition]. PMID- 1462085 TI - [Eating disorders: what kind of management problems for internists and psychiatrists?]. PMID- 1462086 TI - [TIL (tumor-infiltrating lymphocytes): a new therapeutic approach for metastasizing kidney cancer]. PMID- 1462087 TI - [Breast cancer: a practitioner's viewpoint]. PMID- 1462088 TI - [Conservative surgical treatment of breast cancer: a conventional method]. PMID- 1462089 TI - [Breast cancer: impact of treatment and diagnosis]. PMID- 1462090 TI - [Diagnostic approach in an asthmatic patient]. PMID- 1462091 TI - [Inactive gastroduodenal ulcers (asymptomatic). Of what clinical importance are they? Which treatment?]. PMID- 1462092 TI - [Colonic Crohn's disease]. PMID- 1462093 TI - [From hospital geriatrician to practitioner: collaboration and complementary aspects. Results of a survey among practitioners in the Geneva canton]. PMID- 1462094 TI - [Therapeutic impasse in persistent illness]. PMID- 1462095 TI - Genetics of transitional cell carcinoma. AB - Several models of genetic events which define the origin and progression of human tumors have been elucidated over the last several years. These models suggest that the study of tumors at the level of both the chromosome and the gene can be useful in elucidating molecular events in tumor progression and in determining the biologic behavior of individual tumors. The genetics of transitional cell carcinomas are reviewed with emphasis on potential mechanisms of tumorigenicity and the clinical utility of genetic markers. PMID- 1462096 TI - Biology of metastasis: clinical implications. AB - Bladder tumor has a spectrum of neoplastic activity. Some behave in a benign fashion, and others are highly aggressive and lead rapidly to metastatic disease and death. The processes of metastasis can be described as a sequence of interrelated steps. The processes involve 1) tumor cell adhesion to basement membranes, 2) the degradation of basement membranes, and 3) the migration of tumor cells through the destroyed stroma into blood and lymphatic vessels. Each of these processes involves the expression of molecular factors unique to tumor cells. With better understanding of the molecular basis of these factors, novel prognostic and potential therapeutic agents can be generated and applied to the clinical arena. PMID- 1462098 TI - Experimental models of histogenesis and tumor cell heterogeneity in bladder cancer. AB - The histogenetic relationships between the subtypes of bladder cancer are not known. Each common pattern (transitional cell carcinoma, adenocarcinoma, and squamous carcinoma) can exist independently, although they may coexist in primary or metastatic bladder cancers, and tumors that are predominantly composed of transitional cell carcinoma may have regions of squamous or glandular differentiation. Morphologically identical tumors exhibit marked variation in their natural history and response to treatment. To study these aspects of the biology of human bladder cancer, a series of cell lines have been established and characterized as xenografts and in tissue culture. These studies have shown a likely common origin for transitional cell carcinoma, adenocarcinoma, and squamous carcinoma of the bladder. Morphologically similar xenografts and cell lines in vitro have shown a broad range of functional heterogeneity, including ultrastructure, tumor marker production, ploidy, cell surface characteristics, and response to chemotherapy. These are useful models of heterogeneity of response to treatment with established and new cytotoxic agents. PMID- 1462097 TI - Critical review of the models to study the biologic progression of bladder cancer. AB - For transitional cell carcinoma of the bladder, clinical data indicate that invasive, metastatic tumors can arise through at least two different progression pathways. The majority of invasive, metastatic bladder neoplasms clinically present de novo, i.e., the patients have no history of malignant bladder disease. This implies that the highly malignant tumor cells either arise de novo or have undergone a rapid progression. Alternatively, a considerable fraction of patients with superficial bladder cancer process to invasive disease after a history of relatively benign superficial TCC. The molecular and cell biological basis of tumor progression is only poorly understood. Clearly, a better understanding of this progress could have profound clinical implications, since patients with superficial TCC with a high risk for progression would have to be treated more aggressively. We discuss the problems that are associated with tumor biological studies on early steps in the progression of TCC, especially from a "model system point of view." PMID- 1462099 TI - Growth factors and bladder cancer: clinical implications of the interactions between growth factors and their urothelial receptors. AB - Growth factors (GFs) are a class of proteins that bind to specific cell surface receptors (GF-Rs), inducing a variety of responses including mitosis, in susceptible target cells. Abnormal production, expression, and/or function of GFs or GF-Rs can result in unregulated growth, the hallmark of malignant transformation. This chapter reviews those GFs/GF-Rs that have been linked to human bladder cancer. It focuses particularly on one [epidermal growth factor (EGF), which is excreted in urine in high concentrations] and its possible role in the development and growth of urothelial malignancy. Potential clinical applications in diagnosis, staging, prevention, and treatment are discussed. PMID- 1462101 TI - Flow cytometry for detection and evaluation of urinary bladder carcinoma. AB - Flow Cytometry (FCM) DNA assays of bladder irrigation specimens are now recognized as a clinically useful and reliable means of detecting and monitoring carcinoma of the bladder. This technique, which identifies carcinoma by the presence of an aneuploid population of cells, can be carried out on specimens obtained in an outpatient or hospital setting and is easily performed in any medium-sized laboratory. It is most sensitive to superficial and high grade tumors. Overall, nearly 80% of superficial carcinomas of bladder will have positive flow cytometry, comparing very favorably with conventional cytology. Until now, the widest clinical application of FCM has been in monitoring the conservative treatment of stage 0-1 flat and papillary carcinomas, but newly developed dual parameter measurements are capable of quantifying proliferative activity, oncogene expression, growth factor receptors, and other cellular features that may better characterize the biologic potential of these tumors and can be expected to aid in the selection and timing of treatment. PMID- 1462100 TI - Cell surface differentiation antigens of normal urothelium and bladder tumors. AB - Bladder cancer ranks as the third most common malignancy among men and tenth among women. Superficial transitional cell carcinomas (stage Ta, Tis, and T1) account for approximately 70-80% of these tumors, while the remaining 20-30% are invasive (T2, T3, and T4). Approximately 70% of superficial tumors will have one or more recurrences, with 25% of these expressing a higher histologic grade and 10-15% subsequently developing invasive and/or metastatic disease. The detection and prediction of tumor recurrence and/or tumor progression is crucially important if timely and appropriate therapy is to be instituted. Conventional histopathologic evaluation usually provides definitive diagnosis upon which therapeutic planning is based. However, at present there are no more reliable morphologic indicator to identify which individuals will have recurrent disease or who will progress to invasive and/or metastatic cancer. Recent advances in tumor biology have identified markers that are good candidates for clinical applications in early tumor detection, as well as for the stratification of patients with like-appearing morphological lesions with different biological and clinical behavior. The ultimate goal is to develop predictive assays that would segregate patients with high probability of failures versus patients who would be cured by localized modes of therapy. PMID- 1462102 TI - Expression of blood group antigens in bladder cancer: current concepts. AB - Blood group antigens are a group of carbohydrate structures bound to membrane lipids or proteins of erythrocytes and certain epithelial tissues including urothelium. The Lewis antigens are structures that are genetically and biochemically related to the ABO blood group. The ABO and Lewis blood group systems are differentially expressed in the normal urothelium of "secretors" versus "nonsector" individuals. The normal urothelium of "secretors" is rich ABH, Leb, and Ley antigens while the urothelium of "nonsecretors" does not express these antigens. Therefore, deletion of ABH antigens, commonly noted in TCC, can only be reliably ascertained in "secretor" individuals. Neoexpression of the Lewis X antigen (which is absent in normal urothelium) is noted in over 85% of TCC regardless of tumor stage and grade. Immunocytological detection of the Lewis X antigen on exfoliated bladder epithelial cells enhances the detection of urothelial tumor cells, particularly from low grade and low stage neoplasms. PMID- 1462103 TI - Chemotherapy for urothelial tract malignancies: breaking the deadlock. AB - Chemotherapy treatments for urothelial tract tumors have improved to the point that some patients are enjoying long-term disease-free survival. Moreover, with currently available agents and combinations, and with our increased application of clinical and biologic prognostic factors, we are refining our ability to select appropriate therapies for individual patients. We have learned that once the decision is made to use combination chemotherapy, adequate doses should be used. This can be facilitated by the coadministration of hematopoeitic growth factors. Recently completed phase II trials have confirmed that higher doses and dose rates may increase response proportions of and in particular, the proportion of complete responses. The finding that granulocyte colony stimulating factor enhances the sensitivity of tumor cells to methotrexate in vitro and to other agents studied against urothelial tumors implanted in nude mice implies an expanded role for these compounds. However, because non-hematologic toxicities are still important, it is unlikely that simple escalation of all components a four drug regimen such as of M-VAC (cisplatin, methotrexate, vinblastine, and doxorubicin) will have a significant impact on survival. In addition, as more is learned about the pharmacokinetic and pharmacodynamic relationships of the active agents, it appears that better schedules can be designed to improve the therapeutic index of the compounds. Ultimately we will be able to determine drug sensitivities, both at the start of therapy and as it evolves during treatment, that will allow a better selection of a particular chemotherapeutic regimen. For example, mdr1 induction appears to play a significant role in the therapy for treatment-resistant tumors. The availability of a number of active salvage regimens that are not constrained by this mechanism hints that changes in drug sequencing and drug scheduling may provide a significant improvement in outcome. While established combination chemotherapy regimens should be considered standard therapy in appropriately selected patients, promising strategies and new agents need to be investigated if we are to "break the deadlock" that has appeared in the treatment of urothelial tumors. These investigations can be performed safely in a well-controlled fashion to enable the identification of new regimens and to compare promising strategies with appropriate control populations in randomized trials. PMID- 1462104 TI - [Quantification of number and function of mononuclear cells. Fc gamma receptors in children with protein-calorie malnutrition (PCM)]. AB - Several kind of cells T membrane receptors have been recognized, between them immunoglobulins heavy chains receptors mu and gamma, they act in the antigen recognition, they are subpopulations-cells T surface-matched too. In the malnutrition protein-calorie (MPC) immunologic alterations were observed, in both cellular immune and humoral immune, for example: The immunoglobulins are increased and cellular response towards antigens is decreased. This failure can be due to dysfunction in the lymphocyte T-subpopulation. So we research if there are different number, percent and function of lymphocytes T subpopulations between children with MPC and health infant. We observed an increment of lymphocytes T gamma in number and percent in children with MPC compared with health infant (p < 0.05) However, the lymphocytes T and subpopulation gamma response to phytohemagglutinin was bad. These findings are concordant with the literature about increased in lymphocyte T gamma of children with MPC. Additionally we observed a dysfunction in this subpopulation. PMID- 1462105 TI - [Immunoglobulin A and tobacco antigens in patients with pneumopathy]. AB - Smoking is an addiction related with several cardiopulmonary diseases. Some compounds derived from tobacco combustion can be induce a response of secretory immune system, because antigen penetration is by respiratory tract epithelium, with IgA antibodies synthesis and immune complex (IC) generation. Seric anti tobacco antibodies were showed in 44% of healthy smokers and 71% of non-smoker. In 56% of smokers and 38% at non smokers were found IC with 0.19 and 0.15 mg/ml of IgA respectively. Molecular weight of IC constituents were between 12 and 80 Kd. Sera were without free tobacco antigen. Pneumopathic patients had anti tobacco antibodies in 100% of them and positive IC in 72% of smokers and 65% of non-smokers. IgA concentration in CI was 1.41 and 1.26 mg/ml respectively. Molecular weight of IC compounds were from 14 to 90 Kd. Free tobacco antigen in serum was observed in 44% of smokers and 41% of non-smokers pneumopathic patients. We concluded that patients with lung disease had higher frequency of anti-tobacco antibodies and IC, further IgA concentration in IC was higher and free tobacco antigen present in pneumopathic sera comparing with healthy people. The presence of circulating IC with IgA antibodies and the potential inductive influence of tobacco products in these entities, should provide an energetic stimulus to search the role of tobacco antigens in pulmonary inflammatory diseases. PMID- 1462106 TI - [20 years of the National Council of Clinical Immunology and Allergy]. PMID- 1462107 TI - [Symptomatic dermatographism and HLA antigens]. AB - This research reports the unique case of manifestation of symptomatic dermographism which includes all of its twenty five members of the family. Probing a genetic transmission autosomal dominant manner and taking into account the highly probable role of HLA in this illness. The symptomatic dermographism correspond to a group of physical familiar urticarias with symptoms appearing in early childhood and evolving throughout adulthood with seldom periods of remission. Due to the fact that all patients were affected, it was not possible to realize a typification of HLA antigens with persons not affected, to establish a relationship with the data obtained. However, results show a significant association of haplotypes; HLA A2 (78.95), B16 (68.4%), A1 (47.3%), and B5 (42.5%) among the most important. This is the first research that reports the analysis of HLA within the physical familial urticarias. PMID- 1462109 TI - [Ex, post, scoop, spot]. PMID- 1462108 TI - [Sensitization to the acarus Blomia tropicalis in patients with respiratory allergy]. AB - House dust mites are important environmental allergens in Southern Brazil. Some allergic patients do not respond to specific immunotherapy for Dermatophagoides ssp. For that reason we decided to evaluate the skin test sensitivity to tropical mites, Blomia tropicalis and Blomia kulagini. Patients with perennial allergic rhinitis and/or asthma were selected for tests. (N = 135). The wheals cross diameter were recorded. The frequency of strong reactions were 82% for B. tropicalis, 69% for D. pteronyssinus, 56% for D. farinae and 46% for B. kulagini. Wheals were larger with Dermatophagoides sp in 30 patients (22%); similar in 61 patients (45%) and larger with-Blomia sp in 44 patients (33%). Three patients reacted only to Blomia. This study verifies that sensitization to Blomia is common in patients with respiratory allergy. In addition it contains unique allergens that could account for treatment failures with Dermatophagoides in some cases. PMID- 1462110 TI - [3 years of "new developments" in pharmacotherapy. An update which is also a proposal for participative experimentation]. AB - The analysis of the contents of key national and international drug bulletins provides a comprehensive overview of what has been produced worldwide in the field of pharmacology and therapeutics over the last few years after the last publication in R d 1). The work presented, tries to avoid the risk of being a purely descriptive listing of true and false "new" information, and may be seen as an "experiment of information transfer": the available data are presented and summarised from various complementary points of view, to suggest also a methodology of permanent education, for which instruments are also proposed. Further, the text is tentatively proposed as an experiment of communication between nurses and pharmacists, to stimulate their dialogue and interaction both with respect to the use of drug literature and to the evaluation of daily needs of information in routine hospital practice. PMID- 1462111 TI - [The methods and instruments of nursing research: an analysis of some articles]. AB - Three research papers published in three of the most respected foreign nursing journals are presented and discussed. The main aim of the contribution, which opens a new arena for discussion in the Rivista dell'Infermiere is to critically appraise published research works focusing on their strengths and weaknesses in the hypothesis formulation, methods and instruments used, discussion of results. A critical analysis should enable nurses to start to learn to read and eventually write a research protocol, possibly avoiding some common mistakes. PMID- 1462113 TI - [A window on the past: nurses and education]. AB - The history and the state of the art of the debate on nursing education in the first two decades of 20th century is presented. Improvement of nursing education was a strongly felt need from nurses and physicians: feminist movements were strongly in favour of a limited role of physicians in nursing education. Nurses trade unions (Leghe degli infermieri) supported an improvement of nurses' education as a mean to protect patients rights for a better care. Only a minority of physicians opposed the introduction of the English model of nursing care, with the matron who had the power of organizing the hospital. After the advent of fascism the law of 1929 on institution of Scuole Convitto was approved, and this law hindered the development of a reform of nursing education up to the Seventies. PMID- 1462112 TI - [Nursing diagnoses]. AB - The history and the evolution of nursing diagnoses in the USA are briefly presented, together with the main controversies and objections against their widespread introduction and use in Europe. Though the creation of a nursing diagnoses taxonomy might be a very exacting but culturally stimulating task, one of the main problems to overcome is the identification of a theoretical framework. Clinical and theoretical research is needed to validate in our culture the process of formulation and the practical implications of nursing diagnoses identified in the States. PMID- 1462114 TI - [Thrombosis]. PMID- 1462115 TI - [Inhalation therapy and oxygen therapy]. PMID- 1462116 TI - Teleological coherence: exploring the dimensions of the immune system. PMID- 1462117 TI - Anergy and suppression in B-cell responses. AB - Two main ideas have been put forward to explain the unexpectedly low anti-hapten antibody titres which can result from pre-priming a mouse with carrier before hapten-carrier immunization. The first involves the interaction of a network of idiotype-specific suppressor T cells, the second instead arguing for the role of intrinsic B-cell anergy. This paper proposes that the data available can equally be interpreted as reflecting the suboptimal interaction between T and B cells at differing stages of maturity, provided that memory B cells can be divided into two subsets. Further, it is suggested that these considerations must be taken into account in the analysis of B-cell anergy in receptor transgenic mice. PMID- 1462118 TI - Anti-Golgi antibody in rheumatoid arthritis patients recognizes a novel antigen of 79 kDa (doublet) by western blot. AB - We have detected cytoplasmic anti-Golgi antibody (AGA) during a routine immunofluorescence test for detecting autoantibodies. Two sera from patients with rheumatoid arthritis (RA) reacted to the Golgi complex by an indirect immunofluorescence technique on HEp-2 cells. Localization of AGA in the Golgi complex was confirmed by double-staining with antibodies to beta-COP. The effect of monensin on the integrity and morphology of the Golgi complex was also studied. To confirm the presence of AGA further, we performed immuno-electron microscopy. Both sera reacted with cytoplasmic antigen located in the Golgi complex of various animal tissues. Furthermore, by using the Western blot technique, both sera reacted to a relative molecular weight (MW) of 79 kDa (doublet) Golgi antigen purified from rat liver. To our knowledge, this study may be the first to identify the relative MW of Golgi antigen by the Western blot method. Identification of this antibody could provide better understanding of protein synthesis and secretion. The presence of AGA in RA patients further substantiates the diversified nature of autoantibody production seen in this disease. PMID- 1462119 TI - Studies of antibody to herpes simplex virus Fc gamma-binding protein gE in patients with rheumatoid arthritis, juvenile rheumatoid arthritis and normal controls. AB - IgG antibody to gE, the Fc gamma-binding herpes simplex 1 (HSV-1) viral glycoprotein, was studied in 49 rheumatoid arthritis (RA) patients and 43 normal controls. Antibody to gD, another important HSV-1 antigen, was assayed in parallel. No difference between RA patients and normal controls was found in levels of anti-gE antibody measured by reactivity of IgG F(ab')2 fragments reacting with gE coated to ELISA plates. No difference in anti-gD antibody was recorded between normals and patients with RA. Levels of IgG anti-IgE antibody did not correlate with quantitative elevations of serum rheumatoid factor (RF) in RA patients. When IgG anti-gE and anti-gD were assayed in 20 patients with juvenile rheumatoid arthritis and 22 children controls, no significant differences were noted. However, when individual RFs from patients with RA were tested for reactivity against a panel of affinity-isolated F(ab')2 antibodies to gE, some evidence for individual autospecificity was obtained. Four of 20 monoclonal IgM RFs produced from RA patients' B cells showed marked elevations of reactivity with some RA patients' F(ab')2 antibodies to gE. All four of the monoclonal RFs showing this specificity were derived from RA synovial tissue B cells. These findings may provide support for the concept that some RFs in patients with RA show individual specificity for internal image determinants of IgG antibodies to viral Fc gamma-binding proteins. PMID- 1462120 TI - Induction of cellular immune reactions by A36, an antigen complex of Mycobacterium paratuberculosis: comparison of A36 and johnin components. AB - Paratuberculosis (Johne's disease) is a chronic enteritis syndrome of ruminants, which is due to infection by Mycobacterium paratuberculosis. Cutaneous testing with proteins extracted from a mycobacterial culture fluid (johnin-PPD) is currently used to evaluate the cellular immune status. We have compared the components of johnin-PPD with those of the A36 complex, a thermostable macromolecular antigen (TMA) present in the cytoplasm and associated with the cell wall of M. paratuberculosis. The presence in the johnin-PPD of fifteen A36 components has been shown by Western blotting. Moreover, monoclonal antibodies, which bind respectively to the 65-kDa M. leprae heat shock protein, the 28-kDa M. leprae superoxide dismutase, and M. tuberculosis lipoarabinomannan, recognized components of the johnin-PPD. The ability of A36 to trigger delayed hypersensitivity reactions in sensitized rabbits, and to induce the proliferation of T lymphocytes from the lymph nodes of A36-sensitized mice, matched that of johnin-PPD. The homology levels of T epitopes between A36 and the TMA complexes of M. phlei, M. bovis, M. tuberculosis and M. avium were estimated, in a lymphoproliferation assay, to be 51, 52, 59 and 94% respectively. A strong cross reactivity of A36 with an M. leprae sonicate was also observed by cutaneous testing. The A36 components within the 45.2-26.8-kDa and the 21.6-19.8-kDa ranges were proved to induce the proliferation of T lymphocytes from sensitized mice. This work supports the possible use of the A36 complex, and of some of its components, for cutaneous tests and lymphocyte proliferation assays, in order to monitor cellular immunity in Johne's disease. PMID- 1462121 TI - Identification of immunodominant antigens during infection with Mycobacterium tuberculosis. AB - T lymphocytes isolated from mice infected with Mycobacterium tuberculosis response vigorously to proteins secreted by the bacilli and these antigens may be of importance in the generation of protective immunity against the disease. In this study, short-term culture filtrate (ST-CF), which constitutes a complex mixture of secreted proteins, was fractionated by a modified preparative SDS-PAGE technique. The ability of each fraction to be recognized by T cells isolated from infected mice was evaluated by quantifying proliferation and IFN-gamma production in cell cultures. Two molecular mass regions 4-11 and 26-35 kDa were found to possess marked stimulatory properties. Four potent single antigens were mapped within the stimulatory regions. These purified antigens stimulated T cells isolated from mice at the height of a tuberculous infection to produce large amounts of IFN-gamma. Two of these stimulatory antigens belonged to the antigen 85 complex. PMID- 1462122 TI - Cytokine production and responsiveness of fetal T-cell receptor V gamma 3 thymocytes. AB - The aim of this study was to examine the cytokine production and cytokine responsiveness of the first T-cell receptor (TcR) positive cells that appear in the murine fetal thymus, namely TcR V gamma 3 cells. It is shown that IL-2 cultured fetal TcR V gamma 3 thymocytes were capable of producing IL-3, GM-CSF, TNF-alpha and IFN-gamma upon TcR triggering. IL-2, IL-4, IL-5 and IL-6 could not be detected. With regard to cytokine responsiveness, TcR V gamma 3 cells proliferated to a high extent when high concentrations of rIL-2 were added. rIL-4 or rIL-7 alone, but not rIL-1 alone, were capable of inducing a modest proliferation of TcR V gamma 3 thymocytes. When combined with low concentrations of IL-2, a synergistic effect could be observed with IL-1, IL-4 or IL-7. It is shown that the synergistic effect of IL-2 with IL-4 was mainly due to induction of IL-2 receptor expression. The synergistic effect of IL-2 and IL-7 on the proliferation of TcR V gamma 3 cells could only be partially inhibited by anti-IL 2 receptor MoAb, and this antibody had no effect on the IL-2 + IL-1 cultures. These observations can explain the extensive proliferation of TcR V gamma 3 thymocytes during fetal life and they indicate that TcR V gamma 3 thymocytes have the potential to play a functional role during fetal thymus development. PMID- 1462123 TI - Spontaneous in vivo gene transcription of interleukin-2, interleukin-3, interleukin-4, interleukin-6, interferon-gamma, interleukin-2 receptor (CD25) and proto-oncogene c-myc by rheumatoid synovial T lymphocytes. AB - Rheumatoid synovial T lymphocytes were investigated for the presence of mRNA for the cytokines interleukin-2, -3, -4, -6, interferon-gamma, the interleukin-2 receptor (CD25) and the proto-oncogene c-myc. The isolated RNAs were analysed by dot blot and Northern blot hybridization. Our results show that synovial T lymphocytes from patients with rheumatoid arthritis (n = 12) had spontaneous in vivo gene transcription of interleukin-2 (93%), interleukin-4 (67%), interleukin 6 (92%), interleukin-2 receptor (92%) and the proto-oncogene c-myc (67%). Only a few of the RA patients had synovial T cells with increased expression of mRNA for interleukin-3 (25%) and interferon-gamma (25%). The amounts of mRNA for the various cytokines and activation molecules produced by the rheumatoid synovial T lymphocytes were in most instances comparable to those of normal peripheral blood T lymphocytes activated in vitro by the mitogen phytohaemagglutinin. The data thus indicate that the synovial T lymphocytes are activated in vivo in the majority of rheumatoid arthritis patients. PMID- 1462124 TI - A sensitive simple ELISA for quantitation of sensitizing IgG from dissolved erythrocytes. AB - A simple enzyme-linked immunosorbent assay has been developed for quantitating the rabbit IgG present on the surface of sensitized red blood cells. A suitable cell lysis was carried out by an alkaline buffer, which dissolved the erythrocytes without forming any precipitate and without disruption of IgG, and facilitated the dissociation of the immune complexes, i.e. the erythrocyte-anti erythrocyte rabbit IgG. In this alkaline buffer of pH 11.4 the IgG adsorbed directly into wells of microtitration plates unprecoated with anti-rabbit IgG. The detection was performed with alkaline phosphatase-conjugated goat anti-rabbit IgG and p-nitrophenyl phosphate as substrate. Constructing a calibration curve from rabbit IgG made possible the calculation of molecules of IgG bound per red cell. The method was sensitive for the detection of fewer than 500 bound IgG molecules per erythrocyte. PMID- 1462125 TI - Phagocytosis following translocation of the neutrophil b-cytochrome from the specific granule to the plasma membrane is associated with an increased leakage of reactive oxygen species. AB - The effect of neutrophil b-cytochrome translocation on the respiratory burst activation generated during phagocytosis of yeast particles was investigated. Secretion of neutrophil specific granules was induced by the calcium ionophore ionomycin prior to phagocytosis. The secretory process is associated with a translocation from the specific granules to the plasma membrane of the respiratory burst b-cytochrome. Respiratory burst activity was measured as release of hydrogen peroxide in the absence of azide (extracellular leakage) and in the presence of azide (total production). The subcellular localization of the b-cytochrome was found to affect the extracellular release of hydrogen peroxide in that a plasma membrane localization was associated with a significantly increased release during phagocytosis. It should be pointed out, however, that most of the hydrogen peroxide, both in control and in ionomycin-treated cells, is produced intracellularly, probably in the phagosomes. PMID- 1462126 TI - T-cell receptor identification of an oligodendrocyte-specific autoreactive cytotoxic T-cell clone without self restriction. AB - In addition to myelin basic protein (MBP) and proteolipid protein (PLP), oligodendrocyte (Od) membrane autoantigens, such as the glycoprotein M2/MOG, could participate in the pathogenesis of autoimmune demyelinating diseases of the central nervous system (CNS), such as experimental allergic encephalomyelitis (EAE) or multiple sclerosis (MS). We have described an Od-specific autoreactive and cytotoxic T-cell clone, named C2, which recognized M2/MOG without conventional MHC restriction. In order to analyse the Od/C2 interaction, we determined the alpha/beta T-cell receptor (TCR) variable region usages and structures of C2. Monoclonal antibody stainings of C2 and nucleotide sequences show that the alpha chain is composed of a V alpha 5 and a J alpha identical to J alpha 18BBM142 gene segments, and that the TCR beta chain is composed of V beta 17a, D beta 2.1 and J beta 2.2 gene segments indicating that C2 used a conventional alpha/beta TCR for M2/MOG recognition. PMID- 1462127 TI - Quantitative imaging ion microscopy: a short review. AB - A short review of recent efforts being made in the quantification of images in ion microscopy is given. Special aspects of instrumentation, detection and acquisition, which are unique to direct imaging secondary ion mass spectrometry, are discussed in relation to the successful application of traditional empirical quantification schemes. Application of such quantification schemes requires proper sample preparation, standardization, analysis, and quite often, special techniques in image processing and the correlation of ion microscopy with other microscopies. Quantification within this technique is a difficult goal which can only be realized if the analyst pays strict attention to every step of the analytical process. PMID- 1462128 TI - Scanning tunneling microscopy of biological macromolecular structures coated with a conducting film. AB - We have studied the capability of scanning tunneling microscopy (STM) to reveal the three-dimensional structure of biological macromolecular structures that have been rendered conductive by metal-coating. The sample preparation used has been derived from a well established method in transmission electron microscopy (TEM). It includes adsorption, freezing and dehydration by vacuum-sublimation, followed by metal-shadowing of the specimen. As an alternative to adsorption and coating, fluid biomaterials can be replaced by conductive freeze-fracture replica. We give an introduction into the sample preparation of metal-coated specimens and discuss how each step can affect the structural preservation and thereby the quality of the data. Some aspects of the data acquisition and the quantitative evaluation of STM data are shown. Possible contributions of STM in the biological macromolecular research are pointed out. PMID- 1462129 TI - Can we see living structure in a cell? AB - Colloid chemistry (kappa o lambda lambda alpha: glue, or gelatin) was introduced in 1861 after the discovery of protoplasm which exhibits gelatin-like properties. Some 80 years later, colloid chemistry (and with it, the concept of protoplasm) was largely abandoned. The membrane (pump) theory, according to which cell water and cell solute like K+ are free as in a dilute KCl solution, became dominant. Later studies revealed that rejecting the protoplasmic approach to cell physiology was not justified. Evidence against the membrane (pump) theory, on the other hand, has stood the test of time. In a new theory of the living cell called the association-induction (AI) hypothesis, the three major components of the living cell (water, proteins and K+) are closely associated; together they exist in a high-(negative)-energy-low entropy state called the living state. The bulk of cell water is adsorbed as polarized multilayers on some fully extended protein chains, and K+ is adsorbed singly on beta- and gamma-carboxyl groups carried on aspartic and glutamic residues of cell proteins. Extensive evidence in support of the AI hypothesis is reviewed. From an extension of the basic concepts of the AI hypothesis and the new knowledge on primary structure of the proteins, one begins to understand at long last what distinguishes gelatin from other proteins; in this new light, new definitions of protoplasm and of colloid chemistry have been introduced. With the return of the concept of protoplasm, living structure takes on renewed significance, linking cell anatomy to cell physiology. Finally, evidence is presented showing that electron microscopists have come close to seeing cell structure in its living state. PMID- 1462130 TI - Correction for extraneous background in X-ray microanalysis of cell cultures. AB - Some practical aspects of the X-ray microanalysis of cell cultures have been investigated. Cells were cultured on titanium grids covered with Formvar films and analyzed at 100 kV either in the scanning transmission (STEM) or transmission mode (TEM) of the electron microscope. Different holders, grids and configurations were compared with respect to the relative contribution of different factors to the extraneous background in the X-ray spectrum. When low atomic number holders are used, the contribution to the spectrum of electrons scattered through high angles, may be negligible. In practice this may result in negative values for the contribution of these scattered electrons to the background. Computer programs for correction of the extraneous background should ignore these negative values and replace them by zero. When a brass holder is used, the contribution to the spectrum from electrons scattered through high angles becomes more important than that of the uncollimated radiation. The position of the analyzed cell relative to the grid bars is more important than the choice of grid or holder type. The data show that for the specimens used in the present study the correction for extraneous background is of little importance and can be neglected. PMID- 1462131 TI - An improved method for preparing microvascular corrosion casts of rat embryos. AB - This paper presents an improved method for preparing microvascular corrosion casts of rat embryos (day 16.5-21.5). Special attention was paid on the viscosity of the casting material, the method of mechanical restraint, and the subsequent drying of the casts. The embryos were perfused with Mercox resin diluted with 25% methyl methacrylate monomer followed by undiluted Mercox resin to avoid outflow of resin from the vasculature after perfusion. The specimens were mounted on a stainless steel plate with self-curing resin to prevent flotation, mechanical damage, and collapse of the cast specimens following preparation. After digestion and washing, the cast specimens were freeze dried to prevent deformation of the casts. This specimen preparation resulted in much better scanning electron microscopic images of the embryonic microvasculature of various oral tissues, free from leakage and insufficient filling. PMID- 1462132 TI - Scanning electron microscopic studies of the oral mucosa and its microvasculature: a review of the palatine mucosa and its microvascular architecture in mammals. AB - The present paper deals with the microvascular architecture of the palatine mucosa in primates, carnivorae, and rodentia utilizing microvascular corrosion castings and epithelium-separated specimens. The submucous vascular network is under-developed since the hard palatine mucosa was designated the mucoperiosteum, except some areas. The palatine venous plexus appears to show regional differences with animal species differences. The well-developed plexus is observed to be two-layered and may contribute to the process of regurgitation of rough food and assist in mastication with the palatine plicae. Formation and patterns of the arterial network in the lamina propria are in a close relation with connective tissue elements. The subepithelial capillary network constitutes an advanced base for the ascending crus of the capillary loop and its pattern is affected by the properties of the connective tissue papillae and the diverging fashion of the capillary loops. Capillary loops of the transverse palatine plica are arranged parallel to the sagittal axis and at right angles to the top line of each plica. Features of the capillary loops are characteristics in the top, the anterior and posterior slopes of the plica, respectively. High connective tissue papillae in both the anterior slope and plical top may be of a resistant form for mollifying exhaustion, affected by the periodicity and mastication function. Although it is difficult to elucidate the lamination of the palatine mucosa in histological slides, it was resolved by examination on its vascular architectures. PMID- 1462133 TI - Scanning electron microscopy and energy-dispersive X-ray microanalysis studies of early dental calculus on resin plates exposed to human oral cavities. AB - Dental calculus formed after 10 days on resin plates, applied to the lingual sides of the mandibular gingival regions in eight human subjects, was investigated by means of scanning electron microscopy (SEM) and energy-dispersive X-ray microanalysis (EDX). The mineral deposits were mainly divided into three types: A, B, and C. The type A deposits showing an average Ca/P molar ratio of 1.42 were densely packed with fine needle-shaped crystals formed by the intra- and extra-cellular calcification. The type A deposits, probably composed of Ca deficient apatites and the transitional forms between apatite and octacalcium phosphate (OCP), were observed in all subjects. The type B deposits showing an average Ca/P molar ratio of 0.96 were aggregated with polygonal column, triangular plate-shaped, and rhombohedral crystals. These crystals identified as brushite (CaHPO4-2H2O:dicalcium phosphate dihydrate: DCPD) were found in four subjects. Platelet-shaped crystals of the type C deposits were observed in three subjects. Their Ca/P molar ratio of 1.26 and the crystal shape were similar to those of OCP. Whitlockite crystals were not found although Mg-containing hexagonal disk-like crystals were observed in two subjects. PMID- 1462135 TI - Enamel structure in astrapotheres and its functional implications. AB - Astrapotheres, large extinct ungulates of South America, share with rhinoceroses vertical prism decussation in the cheek tooth enamel. The similarity extends beyond merely the direction of the planes of decussation. The vertical decussation in astrapotheres is confined to the inner part of the enamel and has uniformly well-defined zones in which the prism direction differs by nearly 90 degrees and the zones are separated by narrow transitional borders of intermediate prism direction. The outer enamel consists of predominantly occlusally and outwardly directed prisms. Within the outer enamel is a region of horizontally decussating prisms; here the angle of decussation is usually smaller than that of the inner vertically decussating prisms. Except for the horizontal decussation in the outer enamel, these conditions match structures that have been described for rhinocerotoids. These features, together with the similarity in premortem crack direction and gross shape of the cheek teeth, imply that astrapotheres and rhinocerotoids shared essentially the same system of cheek tooth mechanics. However, the microstructure of the canine enamel in the astrapotheres is distinct. The lower canine enamel of the Oligocene Parastrapotherium exhibits a form of vertical decussation modified by a wavelike bending of prism zones, whereas the decussation in the rhinocerotoid canine is horizontal. The lower canine in Parastrapotherium was subjected to different loading conditions, judging from multiple sets of premortem crack directions. The modified vertical decussation would in theory resist cracking under different directions of tensile stresses. This is confirmed by the sinuous paths of cracks that run in directions differing by up to 90 degrees. That diverse stresses were generated in the enamel during life is confirmed by the pattern of premortem cracks in Parastrapotherium. The enamel in the upper canine of a late Miocene astrapothere lacks decussation but may have resisted cracking under varied loading conditions by virtue of a 3-dimensional wavelike bending of the prisms. PMID- 1462134 TI - Scanning electron microscopy-energy dispersive spectroscopy and X-ray diffraction analyses of human salivary stones. AB - Ten salivary stones in the human submandibular gland were investigated by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) and X-ray diffraction analyses. The stones usually showed a lamellar pattern. SEM observations revealed cubical, plate-like, granular, small and large granules, polyhedral or globular structures in these stones. By X-ray powder diffraction analysis, the main constituents of salivary stones were found to be apatite and whitlockite. SEM-EDS analyses showed that Ca and P were the major elements, frequently accompanied by Mg and S, and less frequently by Na, Al, Si, Cl, K, Fe, Cu and Zn. Ca/P molar ratios ranged from 1.00 to 2.00 with the average of 1.53, showing two maxima of about 1.50 and 1.60. The Ca/P molar ratio of about 1.50 corresponded to the value of whitlockite. The Ca/P molar ratio of 1.60 corresponded approximately to the value of apatite. PMID- 1462137 TI - Scanning electron microscopy of the mammalian organ of Corti: assessment of preparative procedures. AB - Different fixation, drying and coating procedures have been applied in preparation of the organ of Corti for scanning electron microscopy (SEM), and structural features of the apical surface of the tissue in unfixed, freeze fractured preparations used in assessing their effects on morphology. Fixation with glutaraldehyde alone or osmium tetroxide alone causes artefacts that are substantially avoided when tissue is doubly fixed in glutaraldehyde followed by osmium. Significant improvements in preservation are also obtained when tissue is additionally processed through thiocarbohydrazide-osmium (TOTO) processing. In addition to providing a conducting coat, it stabilises the tissue against deformations that might otherwise occur during drying, and reduces the extent of tissue shrinkage. Freeze-drying of TOTO processed tissue produces less tissue distortion than critical point drying (CPD) but is not so easy to apply routinely. The distortions of structure in TOTO-processed CPD tissue are not significant and this may be the preferred procedure for routine use, but air drying from hexamethyldisilazane is a useful alternative, producing results as good as those from CPD samples if TOTO processing is applied beforehand. One particular advantage of freeze-drying, though, is that after freezing, brittle fracture through the tissue can occur making examination of intracellular structure by SEM relatively easy. However, again, TOTO processing prior to freezing is of value as this appears to prevent the formation of large ice crystal during freezing. Examination of isolated outer hair cells by SEM shows that isolation procedures do not cause significant damage to the stereociliary bundles. PMID- 1462136 TI - Structure of rat kidneys following microwave accelerated fixation. AB - In contrast to fixation of tissue in externally heated fixative, microwave irradiation can generate uniform internal heat, which is of utmost importance for successful fixation of biological tissue. To evaluate the effectiveness of microwave-accelerated chemical fixation, we compared the structure of rat kidney fixed by a conventional method and a microwave-accelerated method, by scanning and transmission electron microscopy. Following perfusion, rat kidney pieces 1-2 mm in size were irradiated in Karnovsky's fixative in a domestic Amana microwave oven, till the temperature of the fixative reached 45-50 degrees C. For conventional fixation, tissue pieces were fixed overnight at room temperature in the same fixative. Both types of samples were processed further for electron microscopy using identical protocols. The microwave fixed samples showed excellent preservation of structure comparable to the samples fixed by the conventional method. Glomeruli and the renal tubules showed normal morphology with no cellular swelling. The cytoplasm and nuclear matrix of the epithelial cells was uniformly dense. Other fixation sensitive organelles like mitochondria and Golgi apparatus showed superior preservation with continuous membranes. These results demonstrate that microwave accelerated chemical fixation results in excellent preservation of tissue structure, reduces processing time significantly and is therefore a practical alternative to conventional protocols. PMID- 1462138 TI - Review and new case reports on scanning electron microscopy of pili annulati, Monilethrix and Trichothiodystrophy. AB - Pili annulati, Monilethrix and Trichothiodystrophy are uncommon conditions in which the hair shaft has a distinct appearance as seen by optical microscopy and scanning electron microscopy (SEM). We report several new cases and review the characteristic ultrastructural abnormalities investigated by SEM. Pili annulati: abnormal areas which show a longitudinal, "curtain-like" folding of the cuticular cells, alternating with normal areas. The latter present regularly non systematized, superficial depressions. Hair specimens of the patient's mother show the same surface irregularities. Monilethrix: most hair shafts show variations in thickness giving a typical nodal appearance. In the isthmus area we noticed longitudinal ridging and cuticular scales that are extended lengthwise in a fish-scale-like pattern. In the nodus area a smooth surface due to a complete loss of cuticular cells, was observed. Trichothiodystrophy: the hair morphology observed by SEM is characterized by severe cuticular and secondary cortical degeneration along the entire length of the flattened hair shaft, with longitudinal ridging, cuticle loss, trichlorrhexis nodosa formation and trichoschisis. SEM observations show morphological abnormalities which are characteristic for each pathological condition described. This method may provide data that add some clarity in the surface changes of the different hair shaft anomalies. PMID- 1462139 TI - Detection of X-ray damage repair by the immediate versus delayed plating technique is dependent on cell shape and cell concentration. AB - A method commonly used to measure the ability of cells to repair potentially lethal damage (PLD) is to compare immediate plating (IP) and delayed plating (DP) survival. Lower cell survival under IP conditions relative to that after DP conditions has been interpreted to indicate a higher ability of cells to repair potentially lethal damage (PLD) under DP conditions. However, this IP radiosensitization has not been observed in several cell lines and tumor models. IP conditions involve treatment of cells with trypsin and plating them into fresh growth medium. We have investigated the possibility that radiosensitization under IP conditions may be related to both the cell-shape and the nutrient concentration in growth medium (GM, MEM + 15% serum). This idea predicts that the IP and DP survival of spheroids will show a response similar to the IP survival of cells in monolayers and that the IP and DP survival of crowded monolayer cells in high densities will be the same. Chinese hamster V79 cells grown in monolayers (spread cells) and spheroids (clumps of round cells) were used. The IP survival was lower than the DP survival for spread log phase monolayer cells but not for round log phase cells in spheroids. Radiosensitization of cells by fresh (as opposed to spent) growth medium was absent for high density plateau phase cells in monolayers at or above 2 x 10(6) cells/ml. However, PLD repair could be demonstrated in spheroid cells and in high density plateau phase cultures by exposing cells to hyperthermia or hypertonic saline. Comparison of immediate plating versus delayed plating survival detects PLD repair only in well spread low density monolayer cells, but not in round spheroid cells nor in dense monolayer cells at > 10(7) cells/25 cm2 flask/5 ml medium. The absence of a difference between IP and DP cell survival does not mean that PLD repair is absent. Incorrect prediction of tumor response to radiotherapy can occur when PLD repair capacity is assayed as a ratio of DP/IP survival. More than one method must be used to measure the capacity of cells to repair their PLD. PMID- 1462140 TI - Relationship between villous shape and mural structure in neutron irradiated small intestine. AB - Previous work on irradiation of mouse small intestine has assessed the changes produced by counting crypts/microcolonies, scoring villous shape or examining morphological changes in specific parts of the wall. This paper used scanning and transmission electron microscopy to study the effects of whole body irradiation with 5 Gy neutrons on the surface and internal features of the intestinal wall of CFLP mice, 1 day, 3 days and 7 days after treatment. Empirical scores from the ultrastructural findings were inserted into a Morphological Index display calculated from analytical data based on cell counts and area measurements obtained from resin histology sections. The final data display showed that the neutron irradiation produced marked structural changes in different cells and tissues by 1 day. These changes were maximal at 3 days with substantial improvement by 7 days. When this data display was compared with scores taken from scanning electron microscopy of the mucosal surface, the change in villous shape from erect fingerlike projections to lower profiles less suited to absorption was seen to correlate more with changes in the smooth muscle than with the epithelial cryptal compartment. PMID- 1462141 TI - Mechanisms of ciliary movement: contributions from electron microscopy. AB - A brief review of important contributions of electron microscopy to the study of ciliary motility is presented. The electron microscope was used to show the universality of axonemal structure of cilia, and to develop the sliding microtubule model of ciliary motility and later the switch point hypothesis to explain the conversion of sliding into bending. Unexpectedly, insights into the importance of cilia in human health have stemmed from these studies. PMID- 1462142 TI - [Acute severe asthma: emergency diagnostic and therapeutic measures]. AB - There is growing evidence that the prevalence and the severity of bronchial asthma are rising in the industrialized countries despite a marked increase in the sale of antiasthmatic drugs. Non-diagnosis and undertreatment of patients with asthma may be causative factors. Identification of acute severe asthma by the physician and early hospitalization of patients at risk are important factors in lowering morbidity and mortality. Indicators of severe asthma on initial assessment are a history of poor long-term control (previous hospital admissions, regular use of inhaled beta agonists, maintenance oral corticosteroid treatment, prolonged current attack and low or greatly varying peak flow values) and clinical examination with spirometry as the most objective tool. A peak expiratory flow (PEF) of < 30% pred. (< 100-120 l/min) and a forced expiratory volume in the first second (FEV1) of < 25% pred. (< 0.7-1.01) indicate severe asthma. The physical signs and symptoms correlate well with the spirometric values but show too much variability to be used alone. A PaCO2 value of > or = 45 mm Hg (6 kPa) is very specific for severe asthma. Patients whose asthma is considered severe on initial assessment must be referred to a hospital. In the emergency ward the documented response to treatment, i.e. the speed of recovery, is the most important parameter for discharge or admission to hospital. Only patients who improve within a few hours, who remain clinically stable and who have a PEF > 75% pred. or an FEV1 > 50% pred. should be discharged. PMID- 1462143 TI - [Swiss quality control in bacteriology and mycology 1989-1991]. AB - Since 1983 there has been a voluntary quality assessment scheme (QAS) for bacteriology and mycology laboratories in Switzerland directed by the Committee for Quality Control of the Swiss Society for Microbiology. For the first time, the results of this QAS for the period between 1989 and 1991 are made available to a wider public. During the period in question, a steadily increasing number of participants received three samples containing microorganisms four times a year for identification and susceptibility testing. A mean percentage value of a point rating, with a maximum of 12 points, was calculated every year for each laboratory. Values of < or = 75% were defined as insufficient. For a first evaluation, laboratories were assigned to the categories of cantonal (and university) laboratories (C/U), private laboratories (P), and hospital laboratories (H, in hospitals which are neither university nor other tertiary care centres). Significant differences were detected between C/U and P on the one hand and H on the other. As a rule, H obtained poorer results than the two categories, examined fewer specimens, and their percentage with results < or = 75% was significantly higher. The second evaluation classified laboratories according to their recognition by the Swiss Federal Department of Public Health (FDPH). For statistical reasons, H had to be grouped with C/U. Nevertheless, their share of non-recognized laboratories was exceedingly high (15 out of 17 participants in 1991). Recognized laboratories constantly showed a better performance than non-recognized laboratories, examined more specimens, and their number of laboratories obtaining results < or = 75% was much lower.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462144 TI - [New faces, forgotten diseases:border medical examination of asylum seekers' children 1990-1991]. AB - Hitherto there has been no epidemiologic basis for the extent of initial medical examination (IME) of children of refugees. In Switzerland little data is published on the incidence of diseases among refugees; in particular information on their children is scarce. We report the results of IME in these children in the Canton of Zurich from 1 July 1990 to 30 June 1991. The Federal Refugees Office assigned 1487 children to the Canton of Zurich. 920 children (61.9%) were registered, 259 (17.4%) at Zurich Children's Hospital and 661 with local physicians (44.5%). The current IME included a tuberculin skin test only, with additional hepatitis B screening of children from high risk countries. At the Zurich Children's Hospital the IME was extended: every child was examined clinically and a history was taken. The findings in the children examined at the Zurich Children's Hospital were as follows: 171 (66%) were healthy. 5 children (2%) had tuberculosis, 2 (0.8%) vitamin D deficiency rickets, 5 (2%) had iron deficiency anemia, 9 had hepatitis B (all recovered), 25 (9.7%) had various skin diseases and in 51 a variety of diseases of differing clinical significance were diagnosed. The local physicians found a similar incidence of tuberculosis, vitamin D deficiency rickets, iron deficiency anemia and skin diseases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462145 TI - [Long-term course in differentiated thyroid gland carcinoma]. AB - 545 patients with differentiated thyroid carcinoma were followed up for periods ranging up to 25 years after first treatment (mean 8.1 years, 65% for over 5 years). 72% of patients with papillary carcinoma (n = 270), but only 52% with follicular carcinoma (n = 275) remained tumor-free during the further course. Residual malignancies persisted for more than the first year in 6% and 17% of patients respectively; there were tumor recurrences after an apparently tumor free interval in 22% and 31% respectively, the latest after 12 and 27 years respectively. 6% and 19% of patients respectively died as a direct result of the tumor (and a group of equal size from other causes), half due to residual and half due to recurrent carcinoma. With regard to residual tumors, few significant risk factors were found preoperatively, comprising distant metastases (factor = 34 and 20 for papillary and follicular tumors respectively), age over 50 years (F = 6.4 and 5), infiltrating growth of primary tumor (F = 4 and 4.3), and regional lymph node involvement (F = 1.2 and 2). However, these factors were of little use in predicting the risk of the more frequently observed tumor recurrence, with maximum factors of 2 (for T4 and N+ stage) for papillary thyroid cancers and 1.5 for follicular cancers. At risk for recurrence were patients in whom total thyroidectomy was not performed (F = 2.3 and 2) and those who did not receive postoperative radioiodine treatment (F = 3), irrespective of age and tumor stage. Therefore, any individualizing regimen beginning with the first treatment has a bearing not only on residual tumor's 50% contribution to mortality. The equally large contribution of recurrences to tumor death can be influenced only by thyroidectomy or, more realistically, by strumectomy combined with early ablation of thyroid remnants with radioiodine. Postoperative radiotherapy of the neck region did not prevent tumor recurrence, and although hormonal suppression was never given the results compared well with the best of published long-term follow up studies. There were no acute or late complications that could be ascribed to radioiodine treatment. However, a strict strategy of the reducing the administered doses was adopted: the ablation dose was half that used previously (1.5 GBq, i.e. 45 mCi on average), tumor treatment was halted even where residual uptake was observed scintigraphically (in 44% of patients treated) and radioiodine was no longer used for follow-up investigations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1462146 TI - [Boutonneuse fever in Switzerland: apropos of a case report]. AB - The history and clinical presentation of Mediterranean spotted fever in a 72-year old male patient with polycythemia vera are described. The patient presented soon after arrival in Bordeaux (France) with fever, arthralgia and an erythematous maculopapular skin rash involving the palms and foot soles. The clinical course was complicated by pulmonary involvement resulting in dyspnea and hypoxemia. The patient denied tick bite but had contact with a dog. Antibiotic therapy with doxycycline resulted in rapid improvement of all clinical findings. A significant rise in antibody titer against Rickettsia conorii confirmed the diagnosis. The case is discussed in relation to other published cases in Switzerland and illustrates that this infection can be acquired outside an endemic area. PMID- 1462147 TI - [Anatomo-clinical discordance: analysis of a series of consecutive autopsies]. AB - In order to assess the level of agreement between clinical and autopsy diagnoses in the medical wards of a city and teaching hospital, we studied 94 consecutive patients autopsied during a 12 months' period. The rate of autopsy in this study was 59%. The main diagnosis was confirmed at autopsy in 80% of the cases, more precisely defined in 11% and discovered in 9%. Among 124 secondary diagnoses, 34% were diagnosed by the pathologist. The retrospective analysis of the cases in which there was disagreement between clinical and autopsy diagnosis showed that in 8 of them (8.5% of all patients), a clinical impact on survival was possible. However, all of these patients were over 80 and had multiple and/or terminal diseases. Thus, the real impact of these diagnostic errors is debatable. PMID- 1462148 TI - [Hospitalization of tuberculosis patients in Swiss hospitals in 1990]. AB - Despite a wide spectrum of efficient chemotherapies, tuberculosis patients even today are often given inpatient treatment. This fact is shown by the MSV, the Medical Statistics of VESKA (Association of Swiss Hospitals), which is coded according to the ICD key and numbers tuberculosis forms from 010 to 018. The MSV figures for the year 1990 in its associated clinics are: total diagnoses 685,204, principal diagnoses 346,671, number of nursing days 4,613,737 and average stay 13.3 days. At the same time, the following data were registered: total of 1009 hospitalizations with a tuberculosis diagnosis, including 555 patients with a principal diagnosis of tuberculosis. Hospitalizations due to tuberculosis as the principal diagnosis account for 13,995 nursing days, which corresponds to 0.3% of the total. The average hospital stay lasts 25.2 days. In both diagnosis groups, first place is occupied by pulmonary tuberculosis (011) with 67.0% and 70.5% respectively, and among the extrathoracic forms 013-018, urogenital tuberculosis (016) with 6.3% principal diagnosis. The cases with the principal diagnosis of tuberculosis generate (partly calculated, partly estimated) hospital costs of approximately Sfr. 4.9 million and a paid wage total of some Sfr. 1.5 million. In the case of secondary tuberculoses of the 2nd and 3rd position in the statistics, analogous sums of an estimated total of Sfr. 2.4 million are added. It is therefore safe to say that tuberculosis is still not without financial significance in Switzerland.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462149 TI - [Controversial aspects of stage I skin melanomas]. AB - Melanoma is still the most frequent cause of death for diseases arising in the skin. The mortality rate is approximately 25%, tumor thickness, sex and localization being the most important prognostic factors. It is still unclear whether the margin of excision, type of anaesthesia and the pattern of follow-up should be taken into consideration in relation to the individual prognostic groups. PMID- 1462150 TI - [Moderate Paget's disease treated with pamidronate (APD): experience in 43 patients with a single 60 mg infusion of varying duration of 1-to-24 hours]. AB - Pamidronate disodium (APD) given as a single 60 mg intravenous infusion over 24 hours was shown to be an effective treatment for Paget's disease of bone. To further improve the feasibility of a simple treatment that ensures compliance in elderly outpatients (pts), we investigated the effectiveness of a single 60 mg APD intravenous infusion given over 8 hours (12 pts), 4 hours (9 pts) and 1 hour (10 pts) compared with that over 24 hours (12 pts). Infusion rate of APD was 7.5, 15 and 60 mg/h respectively, in comparison with 2.5 mg/h previously. Clinical improvement and biochemical remission were observed in all patients. Side effects, limited to mild transient fever and local transient increase in bone pain, occurred in 9 patients (2-3 pts in each group). There was no difference in the fall of plasma alkaline phosphatase and of urinary hydroxyproline between the 4 infusion rates. Plasma alkaline phosphatase (U/l, mean +/- SEM) decreased from 263 +/- 34 to 110 +/- 8 (1 h infusion), from 251 +/- 26 to 102 +/- 9 (4 h), from 237 +/- 23 to 95 +/- 9 (8 h) and from 256 +/- 29 to 97 +/- 7 (24 h), from day 0 to day 180 respectively (all p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462151 TI - [Diagnosis of hydroxyapatite disease]. AB - The possibility of detecting hydroxyapatite crystals in synovia in a routine setting has been studied prospectively. Coloration of the crystals with alizarin red-S was the method of choice. The diagnostic results were markedly improved by simultaneous observation of a freshly prepared positive control synovia. PMID- 1462152 TI - [The biotransformation of NSAIDs: a common elimination site and drug interactions]. AB - Many NSAIDs are eliminated predominantly through hepatic biotransformation in man. We have studied, in human hepatic microsomes, the role of specific cytochrome P450 isozymes in the formation of the major metabolites of oxicam (piroxicam and tenoxicam), phenylacetic (diclofenac) and propionic acid (ibuprofen) derivatives. A common isozyme (P450TB, CYP2C subfamily) controls the major elimination pathway of these NSAIDs. We have also determined, in two in vitro models of P450TB, the affinity for this isozyme of NSAIDs from other chemical classes (acetylsalicylic acid, mefenamic acid and indomethacin). All NSAIDs tested displayed a high affinity (3-300 microM) for cytochrome P450TB. Cytochrome P450TB plays a major role in the elimination of several NSAIDs with different chemical structures. NSAIDs are substrates as well as potential inhibitors of cytochrome P450TB. Their elimination can therefore be reduced by concomitant administration of known inhibitors of P450TB (antifungals, antibacterial sulfonamides, calcium channel blockers). PMID- 1462153 TI - [Preliminary experience with the Storz Modulith SL 20 lithotriptor in reno ureteral lithiasis]. AB - The authors report their initial results in ESWL of urinary calculi with the Storz Modulith SL 20 lithotriptor, a multipurpose device for both urinary and biliary stone treatment. During 176 sessions, a total of 144 cases (81 renal and 63 ureteral) were treated and then, followed up. The over-all rate free of stones was 86.8% (90.1% for kidney and for ureteral stones). The treatment rate was 1.23 per patient. Auxiliary procedures before ESWL were performed in 7.9% of the sessions: insertion of "double-J" stent or nephrostomy tube; all ureteral stones received "in situ" treatment. Mean number of shock waves per session was 1836.1 (range 300-3020). The maximum voltage on the average reached was 17.1 kv. Sedo analgesia by Diazepam and Ketoprofen was given in 75% of the cases. No serious complications were observed. The experience with this machine is discussed in regard to performance; the advantages of its fluoroscopy and ultrasound guided system of focusing are stressed. PMID- 1462154 TI - Deep dorsal vein arterialization in vasculogenic impotence: our experience. AB - We describe our experience of surgical therapy for vasculogenic impotence, using a technique of arterialization of the deep dorsal vein. This technique was chosen because vascular anastomosis can easily be performed, and because of the possibility of inducing haemodynamic mechanisms which favour the maintenance of rigidity, using venous arterialization. The operation was performed on 22 selected subjects with positive results. 12 patients (55%) reported erections which enabled them to have satisfactory sexual relations one year after follow up. From the data reported we can conclude that penile revascularization, using the technique of arterialization of the deep dorsal vein, in well selected cases of vasculogenic impotence, should be considered a valid alternative to a penile prosthesis implant. PMID- 1462155 TI - [Chronobiological approach to renal colic]. AB - The concentration of lithogenic and antilithogenic substances in urine shows circadian fluctuations. With this investigation we intended to verify the presence of a chronobiologic rhythm of colic pain in urinary tract calculosis. Four hundred and forty seven consecutive patients with a clinical symptomatology related to urinary tract colic pain were studied. They were subdivided according to sex and age (297 M, 150 F; > or = 65 ys 29, < 65 ys 428). Urinary and blood chemical analysis and instrumental examinations permitted to confirm the clinical diagnosis. To evaluate the circadian and circannual variability, acute events were grouped into one calendar year by the month and into a ideal day by the hour of occurrence respectively. Chronobiologic analysis was performed utilising Halberg single cosinor test. The results pointed out that the symptomatology related to urinary tract colic pain presents a circadian rhythmicity either in patients as a whole or in single subgroups (males, females, younger or older than 65 ys). Besides no seasonal variability was demonstrated, perhaps because of the mild climate present in the geographic area in which the study was carried on. PMID- 1462156 TI - [Nutritional status and chronic renal insufficiency]. AB - The occurrence of malnutrition in patients with chronic renal failure has been well documented, mostly in patients undergoing regular dialysis: these patients often suffer from protein-calorie malnutrition, but more seldom there are disturbances to be due to deficit of 1,25 dihydroxyvitamin D3, folic acid, vitamin B6, iron, zinc and L-carnitine, mostly in patients who do not get adequate supplementation. There are several causes for protein-calorie malnutrition in chronic renal insufficiency. These include uremia per se, altered hormonal milieu, abnormal amino acid metabolism due to uremia or to loss of metabolically active renal tissue. Dialysis treatment improves some of these abnormalities, but introduces others. On the other hand, it is well established that morbidity and mortality in chronic renal failure are influenced by their nutritional status: therefore it is important to know the factors and the mechanisms that cause malnutrition for its prevention, recognition and correction. PMID- 1462157 TI - Chronic interstitial cystitis. Successful treatment with intravesical idocaine. AB - A case of interstitial cystitis in a patient with a 5-year history treated by intravesical instillations of Lidocaine is reported. The repeated treatment relieved the patient from her pain and induced a potent anti-inflammatory effect on the bladder wall. The concentrations of plasma Lidocaine were between 1.4 and 1.1 mg/ml. No adverse reactions were reported with a follow-up of 2-years. PMID- 1462158 TI - Angiosarcoma of the adrenal gland. Case report. AB - The vascular tumours of the adrenal gland are rare, both the benign and the malignant ones. Twenty two cases from the literature are reviewed in a paper by Kareti et al., 1988, among which only one own case of angiosarcoma the authors deem to be the first to be reported. A second case of angiosarcoma of the left adrenal gland, in a 67 y. old man, is herein reported. Notwithstanding a through surgical removal, a quick fatal progression of the disease ensued. Perhaps, considering the high malignancy of these rare tumours, an adjuvant form of treatment seems to be advisable. PMID- 1462159 TI - [Oncocytic carcinoma in a horseshoe kidney]. AB - The Authors report a rare case of oncocytoma in a horseshoe kidney. The diagnostic path needed to assess the precise anatomy of the malformation and tumoral staging is out lined. Oncological problems dealing with oncocytoma are further discussed, together with the technical and surgical issues pertinent to the clinical case. PMID- 1462160 TI - Urethral manipulation syndrome (Kelamy syndrome): acquired ventral penile deviation. AB - Fibrosis of the corpus spongiosum penis, caused by urethral manipulation and the resulting ventral penile deviations are known as the urethral manipulation syndrome (Kelami Syndrome). This condition is due to fibrosis and scarring of the corpus spongiosum penis after any kind of urethral manipulation. We have observed 4 urethral manipulation syndromes developing after urethrocystoscopy and presented them. PMID- 1462161 TI - [Early diagnosis and proper treatment of infections of the male genital system]. AB - The appropriate methods for early detection and the more effective drugs for best treatment of "other" Sexually Transmitted Diseases (STD) are reviewed: the most important target is to prevent sequelae of infection like seminal phlogosis, woman's pelvic phlogosis, impotency, sterility. PMID- 1462162 TI - [Intrinsic endometriosis of the ureter. Clinical case]. AB - Endometriosis is defined as the presence of endometrial tissue outside the cavity of the uterus. The urinary tract is rarely affected, only 1 to 11%. Bladder is the most frequent urinary localization while the ureteral involvement is rare. We report a case of intrinsic ureteral endometriosis in a woman with left hydronephrosis, lumbar pain and septic fever. Instrumental and laboratory investigations can hardly lead to a reliable diagnosis of ureteral endometriosis. A final diagnosis is feasible only by histologic examination, which obviously implies surgery. PMID- 1462163 TI - Drug discovery and development in the pharmaceutical industry. AB - The discovery and development of new anticancer drugs is a complex and largely empirical process. New compounds can be discovered by screening, modification of existing compounds, rational drug design, and serendipitous basic research observations. Selection of compounds for clinical trials depends on assays of uncertain predictive value. In the pharmaceutical industry, priorities for development of potentially active entities are set and available resources allocated based on the availability and cost of supplies, patent status, potential spectrum of activity, ability to meet regulatory requirements, and market assessments. Competition for resources also occurs from noncancer drugs, eg, cardiovascular agents. Clinical development (testing and approval for commercial distribution) requires close attention to the requirements of national regulatory agencies such as the United States Food and Drug Administration. The arbitrary nature by which compounds with antitumor potential are chosen for development means that some that would be useful never reach clinical trial and others are never made generally available. This article reviews the decision making process in the pharmaceutical industry by which compounds are identified and selected for clinical trial, the regulations in the United States that govern such trials, and what is required to have the drug approved for commercial distribution. PMID- 1462164 TI - The National Cancer Institute: cancer drug discovery and development program. AB - The discovery and development of novel therapeutic products for the treatment of malignancy is vitally important to those physicians responsible for the management of cancer patients. A description of the ongoing efforts at the National Cancer Institute (NCI) is intended to provide insight into those complex processes necessary to accomplish this mission. An update on the NCI's revised cancer screen is accompanied by a brief summary of those new agents scheduled to be entered into clinical investigation in the near future. The tremendous potential advantages and challenges associated with the use of a molecular approach to cancer drug design are discussed. Despite the differences of opinion that may exist regarding the optimal strategies for accomplishing the mission, there is no disagreement regarding the importance of the effort to find effective new therapies for cancer patients. PMID- 1462165 TI - New vinca alkaloids and related compounds. AB - The vinca alkaloids remain among the most useful classes of anticancer agents used in the clinic today. However, previous analogs of these agents have not realized either increased safety or an enhanced antitumor spectrum. Currently, three derivatives are in clinical trial: vinorelbine, vintripol, and vinxaltine. Vinorelbine has shown consistent antitumor activity in patients with breast carcinoma and is in phase III trials in the United States, Europe, and Japan. Vintripol and vinxaltine, vinca alkaloids conjugated to amino acids, are in early clinical trials in Europe. The dose-limiting toxicity of these agents is leukopenia. A similar agent with a different chemical structure, rhizoxin, is in early phase II clinical trials with initial activity noted in breast carcinoma. The ultimate role of these agents in treatment of human malignancy awaits the results of ongoing studies. PMID- 1462166 TI - The anthracyclines: will we ever find a better doxorubicin? AB - The anthracyclines are the class of antitumor drugs with the widest spectrum of activity in human cancers, and only a few cancers (eg, colon cancer) are unresponsive to them. The first two anthracyclines were developed in the 1960s. Doxorubicin (DOX) differs from daunorubicin (DNR) only by a single hydroxyl group. This fact has spurred researchers worldwide to find analogs of DOX that have less acute toxicity, cause less cardiomyopathy, can be administered orally, and/or have different, or greater, antitumor efficacy. Five DOX/DNR analogs are marketed in other countries, and one (idarubicin) is available in the United States. None of these analogs have stronger antitumor efficacy than the original two anthracyclines, but there are some differences in toxicity. Methods have been fashioned to keep the peak plasma level of DOX muted to minimize cardiotoxicity, but the only apparently effective method available so far (prolonged drug infusion) is cumbersome. The bisoxopiperazine class of drugs (especially dexrazoxane) provides protection against anthracycline-induced cardiomyopathy and has much promise for helping mitigate this major obstacle to prolonged use of the anthracyclines. The DOX analogs being evaluated in the 1990s have been selected for their ability to overcome multidrug resistance in cancer cells. Thirty years after discovery of the anticancer activity of the first anthracycline, some means of reducing anthracycline toxicity have been devised. Current studies are evaluating increased doses of epirubicin to improve anthracycline cytotoxicity, while limiting cardiotoxicity, but at present DOX still reigns in this drug class as the one having the most proven cancerocidal effect. PMID- 1462167 TI - The anthrapyrazoles: a new class of compounds with clinical activity in breast cancer. AB - The anthrapyrazoles are DNA-binding anticancer agents with broad spectrum preclinical activity and reduced potential for free radical generation compared with doxorubicin. In early clinical trials, the dose-limiting toxicity has been leukopenia, other side effects being minor, and promising antitumor activity has been shown, especially in breast cancer. It remains to be confirmed that the anthrapyrazoles are less cardiotoxic than doxorubicin, but it is clear that these drugs are showing real promise, appear significantly less toxic than doxorubicin, and seem to represent a genuine therapeutic advance. PMID- 1462168 TI - Antifolates: the next generation. AB - A number of promising new antifolates have been entered in clinical trials in recent years. These agents have been rationally designed based on the current understanding of folate transport and metabolism and of the mechanisms by which cells become resistant to methotrexate. Methotrexate-resistant cell lines are generally sensitive to one or more of the newer antifolates, which differ from methotrexate by being either more lipid soluble, more extensively polyglutamated, or by inhibiting folate-requiring enzymes other than dihydrofolate reductase. Five of the agents furthest along in clinical testing, trimetrexate, piritrexim, edatrexate, lometrexol, and D1694, are discussed. These drugs offer exciting opportunities to expand the role of antifolates in cancer chemotherapy, as well as in antimicrobial and antirheumatic therapy. PMID- 1462169 TI - The current status of new platinum analogs. AB - Nine platinum analogs are currently in clinical development, including three that contain the diaminocyclohexane substituent and five that contain the cyclobutanedicarboxylato leaving group. Many of them have shown activity in at least one cisplatin (CDDP)-resistant cell line, most commonly L1210 murine leukemia. In addition, most were less nephrotoxic than CDDP in preclinical evaluations. While these agents share certain key structural similarities, there are important differences in their toxicity profiles that may be exploitable in future combination therapies. Though neuropathy has been a troubling toxicity with two of the three diaminocyclohexane (DACH) compounds, it differs in that it appears to be less chronic and cumulative with oxaliplatin (I-OHP), which is also associated with much less myelosuppression. Of the cyclobutanedicarboxylato compounds that are structurally related to carboplatin (CBDCA), there are several notable differences. For several compounds, isolated neutropenia has been dose limiting and thrombocytopenia, which is common with CBDCA, has been uncommon. Like CBDCA, neurotoxicity has not been an issue with this group. Therefore, the potential for dose escalation with a colony stimulating factor (CSF) appears enhanced. Furthermore, promising early clinical leads, such as the substantial response rates in cervix and head and neck cancers with 254-S and in patients with colon cancer using circadian modulation of I-OHP, require careful evaluation. Preclinical synergy data are also cited that suggest other potential clinical leads. The development of a number of these agents has been complicated by unanticipated issues, including unexpected chronic dose-limiting neurotoxicity with ormaplatin (OP), formulation and stability problems with liposomal neodecanoato-diaminocyclohexane platinum (II) (L-NDDP), and problematic nephrotoxicity with zeniplatin (ZP). However, several of these new compounds are likely to enter broader phase II and III development and should provide important information not only about the utility of the agents themselves but also about the predictive value of some of these preclinical models of CDDP resistance. PMID- 1462170 TI - Trans-retinoic acid and related differentiation agents. AB - Interest in retinoids as therapeutic agents has developed as a result of the observations of remission induction with all-trans retinoic acid (tRA) in patients with acute promyelocytic leukemia (APL), and of high objective response rates noted with the combination of cis-retinoic acid (cRA) with interferon-alpha in squamous cell carcinomas of skin and cervix. The therapeutic experience with RA in APL is discussed in this article from the perspectives of new information concerning retinoid biology, observations related to the development of the retinoid syndrome, complex pharmacology of this agent, and possible explanations for development of retinoid resistance. The current National Cancer Institute supported drug development strategy for RA used alone or in combination with other differentiating agents, and the potential therapeutic uses in cancer for other retinoids are also discussed. PMID- 1462171 TI - Research capacity building in international health: definitions, evaluations and strategies for success. PMID- 1462172 TI - Developing partnerships for health and social science research: the International Clinical Epidemiology Network (INCLEN) social science component. AB - A decade after its inception, the International Clinical Epidemiology Network (INCLEN) adopted a social science component. Health social science concepts were added to a physician training curriculum encompassing epidemiology, biostatistics and clinical economics, and a position was created for qualified social scientists at 26 clinical epidemiology units in developing country medical schools. This paper describes the INCLEN model for strengthening partnerships among clinical epidemiologists and social scientists. The rationale for interdisciplinary training is presented along with the difficulties inherent in attracting social scientists to a new career path. These include problems of recruitment, training curricula, re-entry, and career sustainability. The need is identified for collaborative international efforts to promote an infrastructure for professional growth and sustainable careers in health social science. PMID- 1462173 TI - A strategy for promoting improved pharmaceutical use: the International Network for Rational Use of Drugs. AB - Over the last decade, pharmaceutical selection, procurement, distribution, and financing have improved as a result of essential drugs programs. However, despite improved availability, pharmaceuticals are frequently used irrationally. The International Network for the Rational Use of Drugs (INRUD) has been established to help address this problem. The Network joins core groups of researchers from four African and three Asian countries with support groups in Boston, Sweden, WHO, and Australia. The activities of the Network are supported by multilateral, bilateral, foundation donors and by Management Sciences for Health. INRUD functions as a participatory organization in which members are involved in decision-making. The primary objective of the Network is to identify through a coordinated set of country-based research projects a set of effective interventions to recommend as policy options for the promotion of rational drug use. In developing these research projects, INRUD stresses the importance of a multi-disciplinary perspective for adequately understanding the reasons underlying inappropriate use of drugs. To better enable country groups to utilize strong research methodologies and to blend the strengths of multiple disciplines effectively, a major activity of the Network thus far has been the building of local research capacity. PMID- 1462174 TI - The potential of transdisciplinary research for sustaining and extending linkages between the health and social sciences. AB - The last decade of the twentieth century is witnessing a profusion of projects drawing together social and health scientists to study and recommend solutions for a wide range of health problems. The process--practiced in both developed and developing countries--is usually called multidisciplinary or interdisciplinary research. Its historical precedents are briefly reviewed in this paper along with the types of problems addressed. From a review and discussion of a sample of projects selected from two major proponents of this approach to research, the Social and Economic Research Component of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases and the Applied Diarrheal Disease Research Project, conclusions are drawn about the nature of contributions from such efforts--very useful for short-term problem solving, less so for longer-term programmatic changes, especially beyond the health sector, and even more limited in impact on theory building for coping with the changing human condition. The recognition of such limitations is now widespread in the social and natural sciences beyond the health sector, in population, ecology, and the humanities. Following these observations, I argue for a new approach to transcend the disciplinary bounds inherent in multi- and interdisciplinary research. A transdisciplinary approach can provide a systematic, comprehensive theoretical framework for the definition and analysis of the social, economic, political, environmental, and institutional factors influencing human health and well-being. The academic and career challenges for such researchers, while considerable, may be overcome since there is now a new flexibility in research-supporting organizations to encourage new ideas in international health, such as that of essential national health research. PMID- 1462175 TI - Local knowledge: research capacity building in international health. AB - Processes of building research capacity in international health projects and their implications for anthropology are addressed using examples from the Applied Diarrheal Disease Research project funded by the United States Agency for International Development. Two aspects of training are examined: the way interdisciplinary methods--qualitative and quantitative approaches--are presented to researchers, given the context of international health research culture; and how researchers' local knowledge and local concerns in pursuing health research relevant to policy led them to become interested in anthropology. The consequences for anthropology's place and product in future capacity building efforts in international health research are discussed. PMID- 1462176 TI - Manuals for ethnographic data collection: experience and issues. AB - The authors' experience in developing a manual based on ethnographic methods for collecting, analyzing and using information about the 'cultural context of diarrhea' is presented. The goal of the process outlined in the manual is to recommend programmatic strategies and educational messages that are likely to be effective in achieving the adoption of appropriate diarrhea case management behaviors by mothers. The implications of manuals of this type for the role of anthropologists, and for social science capacity building in developing country programs are discussed. While recognizing that this approach risks limiting the anthropologist's role to a technical one, the authors suggest that appropriate application of program specific manuals can encourage anthropological input into formulating program policies and strategies. PMID- 1462177 TI - Building applied health research capacity in less-developed countries: problems encountered by the ADDR Project. AB - As governments and other donors renew their support for research scientists in less developed countries, it becomes important to consider new questions about the process of funding scientific research and scientific researchers. This paper argues that research capacity building is a development goal subject to structural constraints and cultural impediments among both donors and recipients. Using data from one specific research capacity building program, the Applied Diarrheal Disease Research Project (ADDR), we describe a set of constraints among donors, recipient institutions, and individual recipients of research grants. We then describe how ADDR supports its investigators, how it has responded to the identified constraints, and what obstacles it still faces. Research capacity building programs in health would be well-served by focusing more attention on research problem identification, and dissemination and application of research findings. PMID- 1462178 TI - Developing applied medical anthropology in Third World countries: problems and actions. AB - Recognition of the usefulness of ethnographic research in Third World community health projects and programs developed rapidly during the 1980s. As a result, the various agencies and organizations promoting community health programs (UNICEF, WHO, NGOs) have greatly increased their recruiting of social scientists, particularly medical anthropologists, for research and other programmatic activities in primary health care, child survival (especially diarrhea, acute respiratory infections, maternal and child nutrition, infectious disease, and AIDS). However, it has proved very difficult to identify well-trained anthropologists and/or other social scientists for these roles, particularly in Third World countries. This paper examines some of the background of this problem, and presents examples of methodological training (in both qualitative and quantitative research techniques) that seek to increase the skills of social scientists and other researchers in the arena of international community health. PMID- 1462179 TI - Balancing relevance and excellence: organizational responses to link research with decision making. AB - Research faces the challenge of balancing relevance to decision making and excellence in the strict adherence to the norms of scientific inquiry. This paper examines the organizational responses that can be undertaken to promote integration of these potentially conflicting goals. We posit that there seem to be structural barriers to effective communication between researchers and decision makers, such as differences in priorities, time management, language, means of communication, integration of findings and definition of the final product of research. These barriers must be overcome through solutions aimed at the organization of research. In this respect, there are three possible models to approach the tension between excellence and relevance: academic subordination, segregation and integration. Only the latter makes it possible to reconcile the advantages of proximity to decision making with the procedures to assure academic quality. In addition to organizational design and institutional development, a strategy to promote research must include a set of incentives to prevent the 'internal brain drain', that is, the tendency of researchers to move to managerial positions. There are four guiding principles to address this problem: parallel careers, academic autonomy, administrative sacrifice and inverted incentives. The complexities of health problems demand that we create new organizational formulas to finally balance relevance and excellence in research. PMID- 1462180 TI - Theory-driven behavioral intervention research for the control of diarrheal diseases. AB - Essentially all methods to reduce diarrheal morbidity and mortality require behavioral change. Research is required to design, implement and evaluate behavior-modifying interventions. Accumulated experience in the many involved disciplines should serve as a basis for this research. However, each of these disciplines is associated with different research perspectives and analytic assumptions; thus integration of these varied but potentially complementary experiences has been elusive. In the present paper, arguing that such perspectives and assumptions are embodied in discipline-based theory, we have developed a generic framework for the conduct of theory-based behavioral intervention research. We illustrate the application of this framework through two vignettes applying two of the theories and models to the development of hypothetical handwashing interventions. PMID- 1462181 TI - [Education for the diabetic patient: why, for whom?]. PMID- 1462182 TI - [Patient autonomy: role of the nurse]. PMID- 1462183 TI - [To learn dietetics]. PMID- 1462184 TI - [Intensive stages of education]. PMID- 1462185 TI - [Medical information for diabetic patients]. PMID- 1462186 TI - [Information from associations]. PMID- 1462187 TI - [Evaluation of pain]. PMID- 1462188 TI - [Health care for diabetics in 1992]. PMID- 1462189 TI - [Anticipatory grief]. PMID- 1462190 TI - [The eternal youth of Eros or nursing homes for aged couples]. PMID- 1462191 TI - [The body in European societies]. PMID- 1462192 TI - [The disease of diabetes]. PMID- 1462193 TI - [What is an "ethical problem"?]. PMID- 1462194 TI - [Iron: what to do?]. PMID- 1462195 TI - [Pneumococcus]. PMID- 1462196 TI - [Robert Debre Pediatric Hospital]. PMID- 1462197 TI - [Bladder sphincter rehabilitation in the aged person]. PMID- 1462199 TI - [Study program leading to a nursing state diploma]. PMID- 1462198 TI - [Laxatives]. PMID- 1462200 TI - Postoperative changes in the spinal cord in cervical myelopathy demonstrated by magnetic resonance imaging. AB - The relation between improvement of myelopathy achieved by surgery and postoperative spinal cord morphologic changes was investigated by magnetic resonance imaging in 51 patients with cervical myelopathy. In 22 patients, the cord indentation disappeared completely (Type I), in 23 it partially disappeared (Type II), and in 3 it remained unchanged (Type III). In three patients the cord enlarged after surgery (Type IV). With the exception of Type IV, increased restoration of cord morphology paralleled improvement in the myelopathy, suggesting that morphologic changes closely reflect neurologic recovery. In Type IV, notwithstanding the peculiar postoperative reaction, improvement was relatively good, and shrinkage of the cord enlargement was seen after 1 year. This kind of postoperative change has not been demonstrated previously by other conventional imaging methods. PMID- 1462201 TI - Laminoplasty versus subtotal corpectomy. A comparative study of results in multisegmental cervical spondylotic myelopathy. AB - A comparative study of surgical results was used to determine the treatment of choice for multisegmental cervical spondylotic myelopathy. Forty-one patients who received subtotal corpectomy and strut grafting (SCS) and forty-two undergoing laminoplasty were followed up for at least 2 years after surgery. Regarding factors known to affect surgical prognosis (age at surgery, duration of symptoms, severity of neurologic deficit, anteroposterior canal diameter, transverse area of the cord at the site of maximum compression, number of levels involved), the two groups were statistically comparable with each other. The severity of neurologic deficits was assessed by the Japanese Orthopaedic Association scale. Results were evaluated in terms of postoperative score and recovery rate. The difference between the recovery rate and final score between the two groups was not statistically significant. Surgical complications were more frequent in the subtotal corpectomy and strut grafting group than in the laminoplasty group. The most frequent complications encountered in the subtotal corpectomy and strut grafting group were related to bone grafting. Spinal alignment worsened in six patients of the laminoplasty group, but none of them suffered from neurologic deterioration. Another disadvantage of subtotal corpectomy and strut grafting was the longer postoperative period of bed rest needed to secure graft stability. We conclude that laminoplasty should be the treatment of choice for multisegmental cervical spondylotic myelopathy when neurologic results, incidence of complications, and postoperative treatment are taken into consideration. PMID- 1462202 TI - Multidirectional instabilities of experimental burst fractures of the atlas. AB - For the purpose of understanding the acute instability of a burst (Jefferson) fracture of the atlas, the authors produced the fractures experimentally and measured multidirectional flexibilities in seven cadaveric C0-C3 specimens. The flexibilities were measured by the authors' standardized method: they applied six types of physiologically pure moments (up to 1.5 Nm) and recorded the ensuing C0 C2 motions by stereophotogrammetry. The flexibility tests were performed before and after the production of the fracture. The greatest increase in flexibility due to the injury was in flexion-extension (+22.0 degrees, 41.7%). In lateral bending, the increase was 7.7 degrees, or 23.9%. The flexibility was mostly maintained in axial rotation (+4.8 degrees, 5.4%). The increase in motion was due to an increase in neutral zone in flexion-extension, and an increase in the elastic zone in lateral bending. These flexibility results of experimentally produced fractures reflect quite well the acute instabilities seen clinically. PMID- 1462203 TI - Spinal cord evoked potentials in thoracic myelopathy with multisegmental vertebral involvement. AB - Spinal cord evoked potentials were recorded preoperatively from the thoracic epidural space after spinal cord stimulation in 20 patients with thoracic myelopathy with multisegmental vertebral involvement. Waveform abnormalities in spinal cord evoked potentials, namely, positive-going wave or decrease in amplitude, were observed in all cases. Abnormalities, especially in the first negative component of spinal cord evoked potentials, were recorded at the most compressed site in each case. Decrease in amplitude of more than 50% was noted frequently in moderately involved cases, whereas positive-going wave was elicited predominantly in cases of severe myelopathy. Spinal cord evoked potentials should provide information for determining the range of decompression in multisegmental vertebral involvement. PMID- 1462204 TI - Rotation vector, a new method for representation of three-dimensional deformity in scoliosis. AB - Rotation vector for three-dimensional deformity, a new concept in scoliosis, is presented. This vector quantifies three-dimensional deformity in scoliosis. Rotation vectors are calculated between pairs of end plates. Any three dimensional malalignments (scoliosis, lordosis [or kyphosis] and rotation) existing between a pair of end plates should be cancelled perfectly by rotating one end plate against the other about an axis represented by the rotation vector. A rotation vector suggests how the deformity in scoliosis should be corrected three-dimensionally. PMID- 1462205 TI - Intraoperative monitoring for thoracolumbar or lumbar surgery with somatosensory evoked potentials after double stimuli. AB - Somatosensory evoked potentials were after double stimuli on the posterior tibial nerve for the intraoperative monitoring in 58 thoracolumbar or lumbar surgeries. The first cortical positive potential P38 and P'38 after the second stimulus was recorded after double stimuli. Transient decreased amplitude more than 50% or missing potential of P'38 was found in 11 cases. These P'38 changes occurred in five procedures of retracting the nerve roots or dural sacs, three cases of reducing of thoracolumbar fractures, and two procedures of transpedicular screwing. No causative procedure was found in one case. In those 11 cases, 5 showed no abnormality in P38 potentials and 6 cases showed less decreased amplitude in P38 than in P'38. Consequently, P'38, which was evoked by the second stimulus, can be used for the intraoperative monitoring in the thoracolumbar and lower lumbar surgery. PMID- 1462206 TI - Pain provocation at lumbar discography as analyzed by computed tomography/discography. AB - Pain provocation was analyzed in 1477 intervertebral discs in 523 patients subjected to lumbar computed tomography/discography. The relation between pain provocation and the degree of general degeneration and anular disruption assessed according to the Dallas Discogram Description as indices of intradiscal deterioration was investigated. Pain provocation was also evaluated after categorizing the discs by the clinical diagnosis. Pain provocation showed little relation to intradiscal deterioration, whereas a strong relation was found between it and herniated nucleus pulposus. in herniated nucleus pulposus, discs with extraligamentous extrusion or sequestration, large protrusions, maximum protrusion site at the nerve root portion, and herniation routes passing through the central portion of the disc showed a high pain provocation ratio. Pain provocation ratios of discs associated with spinal canal stenosis were extremely low. PMID- 1462207 TI - Pathoanatomy of lumbar disc herniation as demonstrated by computed tomography/discography. AB - Computed tomography/discography was performed in 378 patients (403 discs) with lumbar disc herniation receiving intradiscal therapy. The grade of disc degeneration defined by the Dallas discogram description correlated closely with age. The most common herniation routes ran through the central portion of the posterior aspect of the disc (48.9%), through the paracentral portion (18.6%) and through the entire central portion (9.7%), with these directions parallel to the sagittal plane. However, the intraforaminal and extraforaminal routes (4.2%) passed obliquely to the sagittal plane. The development of these herniation routes has been well explained by the findings of earlier histopathologic and biomechanical studies. Computed tomography/discography was very useful in observing the detailed features of HNP such as the range, site of maximum protrusion and protrusion size. PMID- 1462208 TI - Familial predisposition and clustering for juvenile lumbar disc herniation. AB - The siblings and parents of 40 patients (cases) with lumbar disc herniation (aged 18 years or younger) who underwent surgery at the Department of Orthopaedics at Toyama Medical and Pharmaceutical University Hospital between 1976 and 1990 were examined for incidence of lumbar disc herniation. A total of 120 randomly sampled, age- and sex-matched patients (controls) who were hospitalized during the same period due to extraspinal diseases also were studied in the same manner. A survey of the occurrence of definite lumbar disc herniation was carried out that included 75,237 students in elementary, junior high, and senior high schools in Toyama Prefecture, Japan, covering a mean period of 3 years and 4 months. The incidence of surgically treated lumbar disc herniation among people aged 18 years or younger was calculated, and the expected value of disc herniation was obtained in an age-specific manner, on the basis of the age distribution of encumbrances in the above case-control study. The encumbrances of 18-year-old or younger patients with lumbar disc herniation showed familial predisposition, with an odds ratio of 5.61 in comparison to the controls. It was suggested that there is familial clustering of lumbar disc herniation among the encumbrances of 18-year old or younger patients with lumbar disc herniation. PMID- 1462209 TI - A clinical study of degenerative spondylolisthesis. Radiographic analysis and choice of treatment. AB - Surgical treatment of degenerative spondylolisthesis in 27 patients by means of anterior lumbar interbody fusion and in 14 patients by means of posterior decompression yielded average degrees of recovery of 77% and 56%, respectively. Preoperative analysis of myelograms, and computed tomographies after myelography indicated that anterior shifting of the inferior articular process of the slipping vertebra was the main factor responsible for compression of the nervous tissue in the early stages of degenerative spondylolisthesis. Patients in these stages should be treated by anterior lumbar interbody fusion. In the later stages of degenerative spondylolisthesis, osteophytes on the superior articular processes of the lower vertebra were an additional factor in compression, and patients should be treated by posterior decompression. Computed tomographies after myelography provided the key images for identifying pathologic processes in degenerative spondylolisthesis and selecting appropriate surgical procedures. PMID- 1462210 TI - The mechanical properties of the human L4-5 functional spinal unit during cyclic loading. The structural effects of the posterior elements. AB - Cyclic axial compression-tension tests and cyclic torsional tests were performed on ten fresh human L4-5 functional spinal units to investigate the structural effects of the posterior elements on the mechanical properties of L4-5 functional spinal units. The stiffness of the functional spinal unit increased with the increase of displacement under every loading. This was same in the intact functional spinal units and the functional spinal units after removal of each posterior element, respectively. All the posterior elements contributed to the compressive, tensile, and torsional stiffness of L4-5 functional spinal units. The apophyseal joints had a significant effect on the compressive and torsional stiffness. The effect of the apophyseal joints on the torsional stiffness became greater according to the extent of displacement, whereas their effect on the compressive stiffness was constant. The posterior ligaments (supraspinous and interspinous ligaments) had a significant effect on the tensile stiffness. PMID- 1462211 TI - Hypertrophied ligamentum flavum in lumbar spinal canal stenosis. Pathogenesis and morphologic and immunohistochemical observation. AB - To investigate the pathogenesis of hypertrophy of the ligamentum flavum, 45 cases of lumbar canal stenosis were evaluated by computed tomography scan and pathologic and immunohistochemical studies. The ligamentum flavum along with the medial one-third of the superior facet was obtained en bloc to include the enthesis. Statistically significant differences in transverse area and thickness of the ligamentum flavum were evident compared to the control group (P < 0.01). Pathogenesis of the hypertrophied ligamentum flavum was classified into three major groups: 1) fibrocartilage change due to proliferation of type II collagen, 2) ossification, and 3) calcium crystal deposition. It is stressed that marked proliferation of Type II collagen from the enthesis to the ligament side was revealed in the capsular portion of the hypertrophied ligament. PMID- 1462212 TI - Experimental study of denervated muscle atrophy following severance of posterior rami of the lumbar spinal nerves. AB - The morphologic changes in denervation atrophy of paravertebral muscles after severance of the posterior rami in cats were investigated, using histochemical methods and electromyography. Using a paraspinal approach, three branches of the posterior rami on the left side were cut under microscopy at one, two, or three levels (L2 approximately L4). Muscle atrophy was evaluated, using the percent wet weight and the percent diameter of muscle fibers as parameters. Myosine ATPase stain was used to observe reinnervation. Four weeks after surgery, the range and severity of muscle atrophy increased proportionally to the number of posterior rami severed. Muscle atrophy was revealed at one or two levels caudal to the injured nerve level. At 12 and 24 weeks, muscle atrophy recovered gradually. In more than two-level injury groups, however, recovery of percent wet weight reached up to 80% even after 24 weeks, despite the fact of reinnervation demonstrated in some parts of the denervated muscles. PMID- 1462213 TI - Histopathologic and morphometric study of spinal cord lesion in a chronic cord compression model using bone morphogenetic protein in rabbits. AB - Chronic compressive myelopathy was induced in domestic rabbits by implanting bone morphogenetic protein on the ligamentum flavum of the lumbar spine, and the resulting spinal cord lesion was studied histopathologically. In addition, morphometry of myelinated nerve fibers of the white matter in the pathologic specimens was performed to elucidate the mechanisms of cord injury. No loss of white matter nerve fibers was seen when the cord compression ratio (sagittal diameter/transverse diameter) was > 45%, although 6 months later myelin thinning was present throughout the white matter. When the cord compression ratio was < or = 45%, loss of fibers, particularly of large fibers, was seen in the superficial layer of the white matter, with the nerve fibers remaining after 6 months showing decreased diameters. No motor paresis was evident in any animal. These histologic changes represent the early pathologic condition induced by chronic cord compression. PMID- 1462214 TI - Analysis of spinal cord evoked potential and locomotor function during acute spinal cord compression in cats. AB - The aim of this study was to investigate whether or not conductive spinal cord evoked potentials and spinal cord function change correspondingly with each other. The relationship between conductive spinal cord evoked potentials and locomotor function during acute spinal cord compression in animals was investigated. In decerebrate cats, controlled locomotion can be induced by electrical stimuli in the mesencephalic locomotor region. Conductive spinal cord evoked potentials were recorded at the L3 level of the spinal cord and stimuli were given at the T4 segment. The locomotor function was evaluated through electromyograms of the hind limbs. By compressing the spinal cord at L1, both the conductive spinal cord evoked potentials and the locomotor function gradually decreased. When the first negative potential amplitude of conductive spinal cord evoked potentials was decreased to half the level found in normal cats, locomotor function was injured irreversibly. These results showed that changes in the conductive spinal cord evoked potentials were related to changes in locomotor function. The 50% level of the first negative potential amplitude was considered to be the critical level at which irreversible spinal cord paralysis occurred in the cats. PMID- 1462215 TI - The use of autologous blood in the surgical treatment of spinal disorders. AB - A program of autologous blood transfusion in 101 patients who underwent spinal surgery was analyzed. Autologous transfusion was achieved by intraoperative blood salvage using a cell saver and with predeposited blood. The techniques of predeposition of blood included freezing the blood and using a storage solution. Forty-eight patients had scoliosis and received mainly cryopreserved autologous blood and 53 patients had other spinal diseases. Surgery was performed using only autologous blood transfusion in more than 90% of all patients cases. The program was well tolerated by the patients and easily managed by the blood center staff. There were no severe complications associated with this program. The use of instrumentation and extensive spinal fusion were found to be factors associated with increased intraoperative blood loss. This finding suggests that instrumentation surgery and extensive spinal fusion are indications for autologous blood transfusion. Cryopreserved autologous blood transfusion is an effective method for storing a sufficient volume of blood for scoliosis surgery without affecting the patients' preoperative hemodynamic status. PMID- 1462216 TI - The effects of hyperthermia on the spinal cord. AB - This study was conducted to obtain information about the critical temperature of the spinal cord in hyperthermia produced by radiofrequency waves applied to the spine. The first component of the spinal cord evoked potential was analyzed as an indicator of spinal cord function. The spinal cords were heated by radiofrequency waves to a maximum of 47 degrees C momentarily or for 30 minutes. The temperatures were measured with a thermosensor in the epidural space. In momentary heating, the reductions in amplitude were almost parallel with the increases in temperature. In maintained heating for 30 minutes, at 44 degrees C and below, the amplitudes decreased by one-quarter to three-quarters of the control value in the first 5 minutes and recovered to over three-quarters of the control value in 30 minutes. The amplitudes returned to almost the control value after restoration of normal spinal cord temperatures. At 45 degrees C and above, however, the amplitudes were prominently reduced or disappeared in the first 5 minutes and remained depressed during the remainder of the heating. On normalizing the temperature, the amplitudes did not return to the control value. These results suggest that 44 degrees C in the epidural space is the highest tolerable temperature for normal spinal cord function. PMID- 1462217 TI - Clinical values of intraoperative ultrasonography for spinal tumors. AB - Intraoperative ultrasonography was conducted in 52 cases of spinal tumor, at 7.5 MHz, mainly by means of linear scanning, to evaluate its clinical usefulness. The procedure was effectively applied in such clinical purposes as: 1) locating the tumor, 2) deciding the resectability of intramedullary tumors, 3) deciding the site for intraspinal biopsy or shunt tube insertion, 4) establishing the topical relationship between the spinal cord and the tumor, and 5) differentiating neurilemoma from meningoma. Of 10 patients with intramedullary tumors, 5 (50%) were removed, because extirpation was possible when the spinal cord and the tumor were well demarcated on the ultrasonogram. Intratumorous cysts were found to exist in 73% of neurilemoma and 14% of meningioma cases, enabling the differential diagnosis between the two tumors. Intraoperative ultrasonography is an uninvasive method to reveal intradural and extradural conditions and thus constitutes a valuable diagnostic means to ensure safe and precise spinal surgery. PMID- 1462218 TI - Magnetic coil stimulation of the spinal cord in the dog. Effect of removal of bony structure on eddy current. AB - Magnetic coil stimulation applied to the spine excites the lumbosacral roots rather than the spinal cord itself. To evaluate the mechanism responsible for this phenomenon, the effects of volume conduction on the activation of neural elements were studied. In ten intact dogs compound muscle action potentials could be recorded in the soleus muscle only when the magnetic coil was placed over the cauda equina. After laminectomy and pediculotomy, compound muscle action potentials also could be elicited when the magnetic coil was placed over the spinal cord. These findings suggest that the bony structure surrounding the spinal cord interferes with the spread of magnetically induced eddy currents to the spinal cord. PMID- 1462219 TI - Atlantoaxial fusion with posterior double wire fixation. PMID- 1462220 TI - Atlantoaxial subluxation complicated by diffuse idiopathic skeletal hyperostosis. A case report. PMID- 1462221 TI - Severe cervical myelopathy due to diffuse hypertrophy of the cervical posterior longitudinal ligament. A case report. PMID- 1462223 TI - Reactive sclerosis of the pedicle associated with contralateral spondylolysis. PMID- 1462222 TI - Spinal neurenteric cyst. Report of two cases and review of forty-one cases reported in Japan. PMID- 1462224 TI - Penetration injury of the cervical spinal cord. A case report. PMID- 1462225 TI - A ganglion cyst in the lumbar spinal canal. A case report. PMID- 1462226 TI - Benign osteoblastoma in the vertebral body of the thoracic spine. A case report. PMID- 1462227 TI - Atlantoaxial instability in athetoid-dystonic cerebral palsy. A case report. PMID- 1462228 TI - [Cough paper]. PMID- 1462229 TI - [Unanswered questions]. PMID- 1462231 TI - [Research. Clinical nursing yesterday, today, tomorrow]. PMID- 1462230 TI - [Congress 1992. Criticism of dismissal method]. PMID- 1462232 TI - [Zone therapy in chronic constipation]. PMID- 1462233 TI - [Asylum seekers. Communication is all-important]. PMID- 1462234 TI - [Department management--the other side of the coin. Interview by Kirsten Bjornsson]. PMID- 1462235 TI - [Department management--stubbornness and education. Interview by Kirsten Bjornsson]. PMID- 1462236 TI - [Initiative expect backing]. PMID- 1462237 TI - [Patient information--Volapuk]. PMID- 1462238 TI - [Education--inspiration across borders]. PMID- 1462239 TI - [Hygiene--diapers on the floor]. PMID- 1462240 TI - [Hygiene--handwashing or disinfectant spray?]. PMID- 1462241 TI - [Neonatology--nursing care and nearness]. PMID- 1462242 TI - [Department management--dangerous when economy rules]. PMID- 1462243 TI - Thalidomide retrospective: what did the clinical teratologist learn? PMID- 1462244 TI - The contributions of Widukind Lenz to teratology and science: comments on "Thalidomide retrospective: what did the clinical teratologist learn?". PMID- 1462245 TI - A personal perspective on the thalidomide tragedy. PMID- 1462246 TI - Standardized residuals as a means for detection of growth alteration in the pathologic human fetus. AB - This paper introduces and discusses the use of standardized residuals as a technique for comparing the growth of normal and pathologic human fetuses. Anthropometric measures, radiographic measures, and organ weights were regressed on known gestational age of second- and third-trimester fetuses. Standardized residuals were calculated for a group of potentially growth-impaired fetuses. Use of residuals aids in identification of patterns of growth alteration in specific pathologies. Most important, studying the response of developing organ systems to a variety of insults may elucidate mechanisms of growth regulation in the fetus. We emphasize the special quality of the multivariate measures of the core sample of fetuses from the Akron Children's Hospital collection. PMID- 1462247 TI - Embryotoxicity studies of norfloxacin in cynomolgus monkeys. II. Role of progesterone. AB - Norfloxacin, an orally active fluoroquinolone antimicrobial, has been reported to be embryolethal but not teratogenic when administered to pregnant cynomolgus macaques prior to gestational day (GD) 36 at doses > or = 200 mg/kg/day. Additional studies have been performed in an effort to examine the mechanism responsible for this effect, particularly regarding the role of progesterone (P). The first study (Study I) investigated the effect of norfloxacin administration during early pregnancy (200 mg/kg/day; daily GD 20-30) in the absence of a functional corpus luteum (CL). The CL was surgically removed from 16 gravid females on GD 19 in order to focus on placental-derived P; ten were dosed with norfloxacin and six received vehicle only. Embryolethality was observed for 7/10 (70%) of the treated animals during GD 25-31 versus 0/6 (0%) for controls. A reduction in serum P was noted prior to embryonic loss, although no significant effects on chorionic gonadotropin (CG), 17 beta-estradiol (E2), or P or E urinary metabolites were observed. A second study (Study II) was performed in order to evaluate the capacity of norfloxacin (200 mg/kg) to reduce CL-derived P in both normally cycling and CG-stimulated nonpregnant females (ten treated, ten controls; daily for 8 days). No effects on P production or on luteal phase or menstrual cycle lengths were observed. The third study (Study III) was designed to examine the effect of norfloxacin on the metabolism and excretion of P in nonpregnant females. Silastic P implants were placed subcutaneously in order to maintain constant P levels during a 10 day treatment regimen (200 mg/kg/day; ten controls, nine treated). Five of the controls and four of the norfloxacin-treated females also received 14C-P intravenously within 1 hr of the last dose of norfloxacin in order to study excretory patterns. No significant differences between control and treated groups were observed. The results of these studies combined suggest that the developmental toxic effects observed in prior studies and Study I are specific to pregnancy and directly related to placental-derived P production. PMID- 1462248 TI - Rat hepatic glutathione S-transferase-mediated embryotoxic bioactivation of ethylene dibromide. AB - The embryotoxic effects of ethylene dibromide (EDB) bioactivation, mediated by purified rat liver glutathione S-transferases (GST), were investigated using rat embryos in culture. Significant EDB metabolism was observed with rat liver GST purified by affinity chromatography (specific activity of 188 +/- 11.3 nmol/min/mg protein). The reaction was enzymatic in nature and the conjugation rate was proportional to the concentration of EDB (up to 0.75 mM) and the enzyme present in the reaction medium. EDB activation by 100 units (1 unit = 1 nmol of glutathione consumed per min) of purified rat liver GST caused a significant reduction in general development as measured by crown-rump length, yolk sac diameter, somite number, and the composite score for different morphological parameters (Brown and Fabro methodology). Structures most significantly affected were the central nervous and olfactory systems as well as the yolk sac circulation and allantois. The results of this study clearly indicate that under in vitro conditions, bioactivation of EDB by GST can lead to embryotoxicity. PMID- 1462249 TI - Congenital heart disease in the offspring and maternal habits and home exposures during pregnancy. AB - To test the effect of maternal habits and home exposures during early pregnancy on the occurrence of congenital heart disease in the offspring, 406 cases and 756 controls were studied. The cases included all cardiovascular malformations detected in Finland during 1982-1983, while the healthy controls were randomly selected from all babies born during the same period. Case and control mothers were interviewed after delivery using a structured and pre-tested questionnaire. Maternal overall drug consumption during the first trimester was as prevalent among case mothers (13.3%) as controls (14.6%). Neither was the risk of congenital heart disease associated with maternal use of contraceptive pills, salicylates, diazepam, or sweetening agents separately. Maternal exposures to disinfectants, dyes, lacquers, paints, pesticides, or glues at home were equally prevalent in case and control groups. Several earlier miscarriages was a predictor of an infant born with congenital heart disease (OR = 2.7, CI95 = 1.4 5.3). Maternal ultrasound examination was performed during the first 16 weeks of pregnancy more often among the case group (28.3%) than among the control group (22.0%). However, the association between ultrasound examination and the risk of congenital heart disease in the offspring was not statistically significant (OR = 1.2, 95% confidence interval 0.9-1.7) when adjusted for confounding factors such as the threat of miscarriage in logistic regression analysis. It is concluded that maternal ultrasound examination, intake of some common drugs, and exposure to a number of environmental factors at home during early pregnancy are probably not harmful for the developing fetal heart. PMID- 1462250 TI - Absence of limbs and gross body wall defects: an epidemiological study of related rare malformation conditions. AB - The study is based on almost 10 million births and reports on 215 infants with two unusual malformations: amelia and gross body wall defect. Amelia without body wall defect was present in 116 cases, 67 had body wall defects without amelia, and 32 had both. The total rate was 2.2 per 100,000 births. The infants were divided into five mutually exclusive groups. There were 40 infants (0.4 per 100,000) with agenesis of the body stalk, 18 with amelia and other types of gross body wall defects (0.2 per 100,000), 56 with amelia and malformations other than gross body wall defects (0.6 per 100,000), 41 with amelia (with or without other limb reduction defects) but no nonlimb malformations (0.4 per 100,000), and 60 infants with gross body wall defects of a type other than agenesis of body stalk and without amelia (0.6 per 100,000). A weak trend of decreasing prevalence of these malformations was found during the observation period. Infants with agenesis of the body stalk and infants with amelia combined with other types of gross body wall defects occurred at an increased rate in infants of young women. This maternal age effect is also found with gastroschisis, but not with omphalocele, and may indicate etiological or pathogenetic similarities between gastroschisis and the two former groups of defect. In infants with amelia, additional limb reduction defects could be of any type: transverse, longitudinal, or intercalary. Therefore, amelia may be the end result of different types of disturbances of limb morphogenesis. There was an increased rate of twinning. The relationship with amniotic band syndrome is discussed. PMID- 1462251 TI - Association of paternal alcohol use with gestational age and birth weight. AB - Paternal alcohol use has been associated with a number of adverse reproductive outcomes in laboratory animals and there is one epidemiologic report of a detrimental effect on infant birth weight. To expand the epidemiologic evidence, data from the Child Health and Development Studies were analyzed. Data collected from the onset of prenatal care in 10,232 women enrolled in the Kaiser Foundation Health Plan and residing in the San Francisco East Bay area between June 1959 and September 1966 were available, including information on the mother's report of paternal alcohol consumption and a number of potential confounders. Pregnancy outcomes included preterm delivery (< 37 weeks completed gestation), moderately low birth weight (1,501-2,500 g), very low birth weight (< or = 1,500 g), small for-gestational-age (< 10th percentile of weight for gestational age), and mean birth weight. Paternal alcohol use, analyzed in intervals from 0 to 2.0 or more drinks per day, showed no association with any of the outcomes of interest. Adjusted prevalence odds ratios ranged from 0.7 to 1.5, with no indication of a monotonic dose-response gradient. Mean birth weight was also virtually unrelated to paternal alcohol use. Compared with the earlier report, this population had a very modest level of alcohol consumption. Nonetheless, within the range that was studied there appears to be no association between paternal alcohol use and birth outcome. PMID- 1462252 TI - Development of rat embryos in culture media containing different concentrations of normal and diabetic rat serum. AB - In vitro culture of rodent embryos has been extensively used in the search for teratologic agents, with possible relevance to diabetic pregnancy. However, the high concentrations of rat serum added to the culture medium (approximately 75%) have raised concern that the teratogenic effects of some compounds may be attenuated or masked in this culture system and thereby forced the addition of pharmacological concentrations of the compounds (e.g., D-glucose and beta hydroxybutyrate) to the medium. This issue has been examined in the present study where the effects of different concentrations of rat serum on growth and differentiation of rat embryos were recorded in cultures supplemented with increased concentrations of D-glucose and beta-hydroxybutyrate. The embryonic development was also evaluated after culture in medium supplied with serum from diabetic rats. Compared with normal rat serum, the diabetic serum had an elevated glucose concentration as well as markedly increased levels of triglycerides and branched amino acids, indicating a potentially rich supply of major nutrients for the cultured embryos. Lowering the serum concentration in the culture medium from 80% to 50% yielded progressively retarded embryonic growth but no increased rate of other morphological malformations. At 40% serum concentration, however, there was a sharp rise in the incidence of somatic malformations, in addition to the prevailing growth retardation. When the embryonic growth and development were compared at 50% and 80% serum concentrations, increased D-glucose or beta hydroxybutyrate concentrations caused similar degrees of embryonic dysmorphogenesis. Also, the uptake of each compound by the embryos exposed to elevated levels of the two agents were similar in 50% and 80% serum cultures. There was, therefore, no protection against the teratogenic and growth-retarding effects of increased D-glucose or beta-hydroxybutyrate offered by high serum concentrations in the culture medium (i.e., 80% vs. 50%). Embryos cultured in 50% or 80% diabetic rat serum at 30 mmol/L or 50 mmol/L D-glucose concentration showed similar rates of somatic malformations as did embryos exposed to the same proportion of normal rat serum at similar glucose concentrations. By contrast, the diabetic rat serum amplified the general retarding effects of high D-glucose levels, yielding lower protein levels and somite numbers in embryos from diabetic serum culture than in embryos cultured in normal rat serum.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1462253 TI - Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity. AB - The limb plates and craniofacial regions in rabbit fetuses were examined shortly after the last dose of phenytoin on day 16 after daily administration by gavage with either 150 mg/kg on days 14-16 or 300 mg/kg on days 15-16. Both treatment regimens resulted in similar changes. Histologically, the digital areas of the limb plates showed extensive edema and dilated blood vessels within 2 h. After 8 h, vascular disruption occurred with hemorrhages. At 24-48 h after dosing, mesenchymal necrosis and, on some occasions, amputation of digits was observed. In the craniofacial region, well-defined superficial hemorrhage was seen in the frontal and nasal region at 8 h. Histologically, subectodermal hemorrhage caused by vascular disruption and microfocal mesenchymal necrosis was observed. At 48 h, some fetuses showed severe diffuse intracranial and superficial hemorrhage, resulting in massive tissue damage, also in the central nervous system (CNS). Maternal heart rate, blood pressure, PO2, and PCO2 were also measured in awake pregnant rabbits 6 h after the last dose on day 16 after daily administration with 150 mg/kg during gestational days 14-16. An attempt was also made to measure fetal heart rate in anesthetized rabbits. The maternal heart rate and blood pressure decreased with about 15% in phenytoin-treated animals, resulting in a decrease in PO2 (approximately 15%) and an increase in PCO2 (approximately 15%). A decrease in fetal heart rate was also registered. The results thus indicate that phenytoin exerts its teratogenic effects by inducing fetal hypoxia, leading to vascular disrupture and necrosis of existing and developing structures. PMID- 1462254 TI - Methionine decreases the embryotoxicity of sodium valproate in the rat: in vivo and in vitro observations. AB - Methionine provided in the drinking water of pregnant rats injected with sodium valproate reduced the frequency of resorptions but did not improve embryo growth. Rats drinking methionine supplemented water had approximately twice the level of serum-free methionine and consumed only one-half the volume of water of controls. Using whole rat embryo cultures, the simultaneous addition of methionine and sodium valproate to the medium provided no protection from neural tube defects, nor did the addition of methionine to a medium of serum obtained from rats previously dosed with sodium valproate. However, protection from the teratogenic effects of sodium valproate was afforded by methionine when the culture medium was sera from rats consuming methionine and was particularly striking when embryos for culture were taken from pregnant rats that had been consuming methionine. These observations along with those of others indicated the importance of dietary and culture media methionine levels in evaluating experimental and regulatory teratology studies and suggested the possibility that methionine may play an important role in human teratology where multifactorial causes have been implicated in problems such as neural tube closure defects. PMID- 1462255 TI - Histochemical and immunohistochemical distribution of glycosaminoglycans, type II collagen, and fibronectin in developing fetal cartilage of congenital osteochondrodysplasia rat (ocd/ocd). AB - The osteochondrodysplasia rat (ocd/ocd) is a lethal dwarfism. The ocd/ocd shows histological abnormalities of the epiphysis, characterized by a decrease in amount of glycosaminoglycans (GAGs) in the extracellular matrix (ECM). The present study describes histochemical and immunohistochemical distributions of GAGs, type II collagen, and fibronectin (FN) in abnormal humeral cartilage of the ocd/ocd fetuses on days 16-21 of gestation. A wide-spread region with severe necrosis was observed in the cartilage on days 20 and 21. The affected cartilage has small amounts of ECM, irregular columnizations, thinner hypertrophic zones, and expanded and pyknotic chondrocytes on days 16-21 of gestation. The severely expanded chondrocytes did not have cytoplasmic glycogens on days 19-21. Reactions for chondroitin sulfate (CS) and hyaluronic acid (HA) in the ECM were consistently lower in ocd/ocd than in +/+ during the entire period of observation, although there were granules immunoreactive to CS within the chondrocytes of ocd/ocd. The distribution of type II collagen seemed normal in relatively normal regions in the affected cartilage. Strong reactions for CS, HA, type II collagen, and FN were present in the necrotic region on days 20 and 21 of gestation. These findings suggest that the affected chondrocyte may have some defects in releasing ECM substances, which may be released by the process of cell rupture. We hypothesize that some defects in releasing processes inherent to the ocd/ocd cartilage may relate to cellular differentiation and cell death. PMID- 1462256 TI - Empathy and compassion: tools to combat stresses of an illness. PMID- 1462257 TI - The physician's guide to medical waste regulations--Part IV. PMID- 1462258 TI - Court releases opinion concerning abortion. PMID- 1462259 TI - Can managed care control costs without controlling you? PMID- 1462260 TI - Prevalence of human immunodeficiency virus infection in hospitalized adults at a teaching hospital in west Texas. AB - The prevalence of infection with human immunodeficiency virus (HIV) among hospitalized adults at a teaching hospital in West Texas was estimated by conducting a serological survey. Of the 2,458 patients tested, 12 (0.5%) were seropositive. All 12 were men of ages 28 through 50 years; 11 were white and 1 was Hispanic. Eleven were previously known to be HIV positive and were hospitalized for illnesses related to acquired immunodeficiency syndrome (AIDS). All seropositive patients were hospitalized on nonsurgical services of internal medicine, medical-surgical neurology, and family practice. These results indicated that the sampled population in West Texas showed a relatively low prevalence of HIV infection and that seropositive patients were predominantly white men hospitalized for AIDS-related illnesses. PMID- 1462261 TI - Baylor Research Institute also adds to research effort. PMID- 1462263 TI - The abortion issue: a "battle worth fighting". PMID- 1462262 TI - Risk factors for infection with human immunodeficiency virus among low-income women undergoing voluntary sterilization. AB - Data regarding risk for infection with human immunodeficiency virus (HIV) were collected from 486 women who presented in 1989 for tubal sterilization through a clinic operated by a medical school. This clinic was participating in a blind surveillance project administered by the local health department. The project was designed to estimate the prevalence of seropositivity for HIV among women seeking family planning services within the department's catchment area. The expectation was that the population of women choosing voluntary sterilization would be of relatively low risk for HIV infection. Surprisingly, however, when they were examined, nearly 25% of these women reported at least one identified risk factor for HIV infection. The rates for certain specific risk factors are no lower among these women than among the general population. PMID- 1462265 TI - TMA battles problems at Workers' Comp Commission. PMID- 1462264 TI - Heads up: legal case may affect valuing of medical practices. PMID- 1462266 TI - Agenda on AIDS. PMID- 1462267 TI - A need for balance: preventive and therapeutic medicine. PMID- 1462268 TI - Physicians can avoid penalties by posting required safety signs. PMID- 1462269 TI - Laws address issues relating to HIV-positive doctors, health-care workers. PMID- 1462270 TI - Approaching families for organ donation: physicians are willing. AB - While current literature documents a critical disparity between the increasing demand for organs for transplantation and the relatively static supply, reasons for the shortage of donors are not well understood. Public opinion surveys describe a population willing to donate, but consent rates reported by organ procurement organizations suggest problems in the process of approaching families. This study of Texas physicians regarding their knowledge of laws related to brain death and to routine inquiry for organ donation and their attitudes toward the critical step of seeking consent from families indicates that physicians need more information about questions asked by families, would benefit from more structured hospital policies on routine inquiry, feel that physicians rather than nurses should approach families, and believe that the public is not well informed about donation. PMID- 1462271 TI - Health expenditures in Texas, 1988. AB - Expenditures for health care in Texas during 1988 totaled $32.4 billion. Health spending by category of service and sources of payment was estimated and compared with estimates for prior years and with national trends. Texas differed from the nation as a whole in average annual increases in total spending, the percentage of spending for prepayment and administration, and the percentage of spending paid by consumers, the federal government, and private insurance. Proposed expansions in insurance coverage for the large proportion of uninsured Texans will probably require strong efforts to contain costs. PMID- 1462272 TI - It's time to ration health-care technology. PMID- 1462273 TI - Sunset is golden opportunity to make changes at TSBME. PMID- 1462274 TI - RBRVS: the first 6 months. PMID- 1462275 TI - The tactics are the crime. PMID- 1462276 TI - Relationship between the immune system and the diseases of the central nervous system. AB - Considering the eventual role of non-specific cell-mediated immune reactions in the pathogenesis of Parkinson's syndrome based on the destruction of dopaminergic cells of the substantia nigra the killer cell activity of patients suffering from this disease has been examined. According to the results the killer cell activity of Parkinson patients is significantly lower in the age group below 60 years as compared to the higher age groups. When comparing the age groups below 60 years, significantly lower activity was measured in the patients than in the controls. Killer cell activity is significantly higher in patients suffering from more severe conditions (Hoehn-Yahr's stage IV-V) when compared to the milder cases. These results suggest the possibility that killer cell-mediated ADCC reaction may play a role in the pathogenesis of the disease. The results of these examinations open new therapeutic perspectives. It may be hoped that, as a result of our increasing knowledge and technical progress in immunology, the damaged immune system could be selectively influenced and target specific immune therapy could be used in the near future by means of for instance inactivations of cytotoxic cells, elimination of antibodies or other immunological methods. PMID- 1462277 TI - Anti-anginal effect of Tenormin (atenolol). AB - The anti-anginal effect of Tenormin (atenolol) has been examined besides placebo control by single blind method in 20 patients with ischaemic heart disease, suffering from stable effort angina proved by coronarography. It has been observed that atenolol significantly decreases the weekly number of anginal attacks, and the amount of sublingual nitroglycerin consumption. It has been proved that atenolol successfully prevents the exercise-induced elevation of blood pressure and heart rate, increases exercise tolerance, decreases myocardial O2 consumption. The place among beta-blockers of the cardioselective, low lipophilic atenolol, which lacks membrane stabilizing and partial agonist activity, has been discussed. The administration of a single daily dose (one 100 mg tablet), selective cardiac effect, lack of unwanted side-effects (cold extremity, nightmare, insomnia, etc.) are the advantages of the drug. PMID- 1462278 TI - Several years observations with Mydocalm muscle relaxant in locomotor disease patients. AB - Two therapeutic methods were compared on locomotor disease patients; the currently used anti-inflammatory complex therapy and the same therapy complemented with Mydocalm. On the basis of the changes of pain indices and motion indices chosen as parameters it could be concluded that Mydocalm is a valuable adjuvant, especially in improving locomotor functions, and it promotes the improvement of the general condition of the patients and the performance of their daily activities by relieving muscular hypertonia and contractures. PMID- 1462279 TI - Use of pefloxacin in urogenital infections. AB - Forty-three patients suffering from acute or chronic urinary tract infections have been treated with pefloxacin at the Department of Urology of St. Istan Hospital. Twenty-three patients received oral doses (2 x 400 mg), 1 tabl. in the mornings and 1 in the evenings. Eighteen patients were given 2 x 1 intravenous ampoule (2 x 400 mg) dissolved in 250 ml 5% glucose in slow drip infusion. Both the oral and intravenous doses were given in the patients for 10 days. In two patients complications was observed--in one case rhagades were formed on the lip and face due to photo-sensibilization, in the other case the drug administration had to be discontinued because of nausea and vomiting. These symptoms ceased after the discontinuance of the drug. The clinical conditions, the routes of administration, clinical and bacteriological results are summarized in tables. On the basis of a low number of cases it has been concluded that pefloxacin is a new valuable antibacterial drug the use of which resulted in recovery in 15 out of 18 patients' acute and chronic infections of the urogenital system. PMID- 1462280 TI - Haemodynamic effect of nitroglycerin spray. AB - 1. It is a reliable nitroglycerin (NTG) form influencing circulation and haemodynamics like other nitroglycerin products, 2. It is easily applicable, 3. Its use is advantageous especially for the prevention of pressure elevation occurring in response to physical exercise thus for the prevention of effort angina as well, 4. It is a reliable drug to be used in haemodynamic laboratories for measuring nitroglycerin effect, 5. Due to the rapidly developing fall of end diastolic pressure caused by the product it is also of value in controlling cardiac asthma attacks. PMID- 1462281 TI - Estulic--a well tolerated and effective antihypertensive drug in general practice. AB - The results of the treatment of 28 patients with mild to moderate hypertension using guanfacin (Estulic) monotherapy and of 24 patients receiving combined antihypertensive therapy containing Estulic are reported on. The blood pressure was lowered and stabilized during the first month of therapy. No addiction or loss in effectivity was seen. There were no changes in ECG or laboratory results during the mean follow up time of 11 months. Four patients discontinued the drug because of subjective side-effects. The single daily dose, the reliable effectivity, the safety of the drug makes it an important antihypertensive drug in general practice. PMID- 1462282 TI - Mydocalm treatment of muscular and vascular complaints accompanying climacterics. AB - Coated Mydocalm tablet, known as striated muscle relaxant and peripheral vasodilator, has been used in climacteric women. The women suffered from muscular and vascular complaints besides the common symptoms of decreased or lacking ovarian function which could not be controlled with oestrogen substitution therapy. Mydocalm significantly moderated these complaints without causing unwanted effects and the majority of the women could be maintained in a complaint free condition in this respect. According to the opinion of the author the drug is a valuable adjuvant to an adequate hormone therapy. PMID- 1462283 TI - Observations with a tri-phasic oral contraceptive (Tri-Regol) in everyday clinical practice. AB - The theoretical general principles of triphasic oral contraception are discussed in the introduction. This method, which is the closest to a physiological dosage, seems to be the most advantageous today. International data and the advantages and wide indication field of such "step-up" tablets are also discussed. The observations with the Hungarian Tri-Regol tablet are described in detail. In the course of controlling 355 cycles of 79 women pregnancy was not observed, the tablets were well tolerated by the women-except for some milder side-effects. The use of Tri-Regol needed not be discontinued due to, any unwanted effect or complication. The rate of intermenstrual bleeding was very low, and the triphasic therapy proved to be beneficial in case of manifesting cycle disorders or if the change of the contraceptive tablet became necessary because of intolerance. According to the opinion of the authors the oral contraceptive Tri-Regol is today's drug of choice due to its reliable ovulation inhibitory action, low hormone content, and favourable tolerability. PMID- 1462284 TI - Some indications for the gynaecological use of budesonide (Apulein). AB - Budesonide-containing Apulein ointment has been used for the treatment of 29 women suffering from vulvitis, pruritus vulvae caused by vaginal discharge, gestational inflamed hemorrhoid, hymenitis, and late postoperative suture inflammation. The ointment rapidly and completely controlled local infiltration and the accompanying subjective complaints. It did not cause local alteration, the consistency of the ointment met the requirements and it did not disturb the patients' making their toilet. According to the author's opinion the product is a potent antiphlogistic which proved to be a valuable adjuvant to target specific treatment of inflammatory processes of the external female genital organs and perianal regions. PMID- 1462285 TI - Bicentenary of Theophyl Janos Fabini's birth. PMID- 1462286 TI - [Ethical problems of trials of drugs against chronic diseases]. PMID- 1462287 TI - [Informed consent. A myth--or a strait-jacket for policy control?]. PMID- 1462288 TI - [HELLP--still a syndrome]. PMID- 1462289 TI - [HELLP syndrome--a life-threatening pregnancy complication]. AB - A serious complication to pregnancy-induced hypertension and preeclampsia is the HELLP syndrome (H - haemolysis, EL - elevated liver enzymes, LP - low platelet count). Perinatal and maternal mortality are reported to be high, 7-60% and 2 24%, respectively. A non-obstetric diagnosis is often made, such as gastrointestinal or haematologic disease. Typical symptoms are epigastric and right upper-quadrant pain and tenderness, nausea and vomiting. Recognition of the clinical and laboratory findings is important, so that early, aggressive therapy can be initiated in order to prevent maternal and perinatal death. We present data from 14 patients with the HELLP syndrome treated in our hospital. There was one intrauterine death. The other infants were discharged in good condition. Two of the patients had eclampsia. PMID- 1462290 TI - [HELLP syndrome--4 case reports]. AB - HELLP-syndrome (H - haemolysis, EL - elevated liver enzymes, LP - low platelet count) is a serious complication of pregnancy. It can be considered as a variant of severe preeclampsia, where haemolysis, hepatic damage (elevated liver enzymes) and thrombocytopenia (low platelets) are all present. Four case reports of HELLP syndrome are described. HELLP-syndrome may develop within a few hours. It can be seen pre-, intra- and postpartum. Many patients do not exhibit a clinical picture of severe preeclampsia. Patients who develop HELLP-syndrome usually complain of malaise, nausea, epigastric pain and headache. The diagnosis is confirmed when haemolysis, elevated liver enzymes and thrombocytopenia are demonstrated. Patients with HELLP-syndrome require intensive care by a team of obstetricians, anaesthesiologists and haematologists. PMID- 1462291 TI - [Organ donation from recently deceased patients. Experiences from a donor hospital and suggestions for handling potential organ donors and their relatives]. AB - Homologous organ transplantation using organs from patients suffering complete destruction of the brain and brain stem is a major achievement in modern medicine. The care of potential organ donors and their relatives is complex and very demanding for the medical team and nursing staff. In Norway the law sets very clear criteria (documentation of total irreversible brain and brain stem injury) for performing donation. As a rule consent from the family is asked for, although not legally required. This article deals with the problems related to the treatment of potential organ donors. We give practical guidelines for medical staff on how to prepare the patient and his/her family, with emphasis on the human and psychosocial aspects. Preservation of the donor and the organs is not discussed. PMID- 1462292 TI - [Postrenal acute renal failure with deficient or minimal dilatation of the renal pelvis]. AB - This article presents the clinical and radiological findings in three patients with acute obstructive renal failure. In a setting of typical clinical symptoms of acute postrenal obstruction, the lack of or only minimal ultrasonographic dilatation of the pelvicalyceal system should not lead to the conclusion that there is no obstruction until supplementary invasive procedures have demonstrated open urinary tracts. Minimal pelvic dilatation in acute obstructive renal failure is typically associated with malignant diseases encasing the distal parts of the ureters, retroperitoneal fibrosis, urinary calculi and urinary infections. Various pathophysiologic mechanisms are discussed. PMID- 1462293 TI - [Treatment of stomach ulcer with bismuth subnitrate, oxytetracycline and metronidazole]. AB - 60 patients with recurrent duodenal ulcers were treated with bismuth subnitrate, oxytetracycline and metronidazole. Helicobacter pylori status was assessed before and after treatment by means of the 14C-urea breath test. All patients were helicobacter positive before treatment. Four weeks after cessation of therapy H pylori had been eradicated in 57 out of 60 patients (95%). The ulcer healing rate was 100% after six weeks. 43% of the patients complained of moderate to severe side effects, mainly nausea and diarrhoea, but no patients discontinued the treatment prematurely. The study indicates that nearly all patients with recurrent duodenal ulcer are infected with H pylori, and that the present triple treatment regimen is very effective both in eradicating H pylori and in healing the ulcer. PMID- 1462294 TI - [Congenital short Achilles tendon. A survey of habitual toe-walking in children]. AB - Congenital short tendo calcaneus is seen in children as partial or complete walking on the toes, and may represent a major disturbance for normal motor development and coordination. This clinical finding may indicate a more serious, underlying disease (cerebral paresis, childhood psychosis or a neuromuscular disorder). If the patient, apart from walking on the toes exhibits normal clinical findings, the diagnosis of congenital short tendo calcaneus may be justified. The disease may be inherited. The diagnosis should be made by an orthopaedist, and the treatment is either conservative with aggressive physical therapy, or surgery. The prognosis is good after early diagnosis and special treatment. A review of the literature, with emphasis on diagnosis and treatment, is presented, together with a brief review of five patients operated by the authors. PMID- 1462295 TI - [Quality assurance in clinical trials. Problems related to patient information]. AB - In connection with a phase-III study of cholesterol lowering agents, a questionnaire survey was carried out on information to patients' during clinical trials. The survey included 124 patients and nine team members with different professional backgrounds. The results show that, in spite of the fact that the patients had received information in accordance with the guidelines, only 47% of them had perceived that conventional treatment would be offered to those who dropped out of the study. A test of the extent of the patients' understanding about the drugs they were taking showed that only 39% knew how the drug acted and the reasons for the chosen dosing schedule. 23% of the patients would like to have received more information, but 9% of these had problems in formulating questions to the health personnel. Anxiety was a problem for 16% of patients, especially in the early phase of the clinical study. Only half of the team members were aware of this. 45% of the patients felt that they would disappoint the team if they expressed a wish to drop out of the study. Most of the team members would have tried to motivate the patients to continue to participate in the trial. Based on the results of the survey, we suggest some main elements of standard procedures for providing information to patients in connection with clinical trials. PMID- 1462296 TI - [Quality assurance in laboratory medicine--reality and challenge]. AB - So far, quality assurance in laboratory medicine in Norway has concentrated mainly on results. As yet, however, much still remains to be done, particularly in the fields of pathology, radiology and nuclear medicine. Insufficient emphasis has been paid to quality assurance of the requests made for tests and interpretation of the results. Important for this part of quality assurance are teaching and education, cooperation between the laboratory physician and the clinician, more active participation of the laboratory physician in the solving of clinical problems and a change from menu-oriented to problem-oriented requests. PMID- 1462297 TI - [Bone density measurements in prevention of femoral neck fractures]. AB - With a view to preventing hip fractures, bone mineral density measurements have been suggested as a means of selecting individuals at risk. We suggest two focuses in a preventive strategy: selection and information. The overlap in mineral density distributions among women who experience hip fractures and those who do not leads to a high number of inconclusive measurements as regards placing individuals into two such groups. The measurements should therefore be used primarily to inform individuals about their risk. In order to evaluate this technology, prospective studies on bone mineral density measurements prior to oestrogen hormone replacement therapy are highly desirable. PMID- 1462298 TI - [Alcohol consumption among convicted drivers]. AB - 150 males imprisoned for drunken driving were assessed by means of a questionnaire and medical examination. The objectives were to study alcohol consumption and frequency of alcohol-related problems. Half of the assessed persons were less than 30 years of age. 62% had a blood alcohol concentration > 1.50%. 36% had previously been convicted for drunken driving. Average alcohol consumption was 58 gram per day. 40% of the convicted persons reported a consumption of more than 40 gram alcohol per day. Corrected for under-reporting the consumption was even higher. The CAGE questionnaire was positive in 54%, indicating an alcohol-related problem. GGT (gamma-glutamyltransferase) was elevated in 23% and CDT (carbohydrate deficient transferrin) in 35%. This study indicates that 50-60% of convicted drunken drivers were excessive drinkers or/and had alcohol-related problems. Imprisonment and fines seem to have a limited impact on occurrence of drunken driving. Other strategies are discussed. PMID- 1462299 TI - [Ingvald Undset's disease]. PMID- 1462301 TI - [Drug abusers can be rehabilitated]. PMID- 1462300 TI - [6,000 flashes per minute]. PMID- 1462302 TI - [Sudden infant death and the lying position]. PMID- 1462303 TI - [How do we determine the duration of pregnancy?]. PMID- 1462304 TI - [Fractioned abrasion--ritual or rational?]. PMID- 1462305 TI - [Pain in infants]. PMID- 1462306 TI - [Pain and pain relief in neonates and infants]. AB - We review the development of the anatomical and physiological basis for nociception. We point out the ability of babies, even those who are born very prematurely, to feel pain. Procedures which would be painful to older children and adults are also painful to newborns and infants. A sick infant in intensive care may be particularly sensitive to the destabilizing effects of pain, and analgesics will very often be indicated in such infants. We discuss various types of analgesia suitable for infants, and doses of commonly used analgesics. PMID- 1462307 TI - [Head injuries with delayed intracranial hemorrhage]. AB - Nine cases of delayed intracranial haematomas were found among 300 patients with head injuries during a two-year period. Six of the nine patients developed delayed traumatic intracerebral haematoma, two epidural haematoma and one subdural haematoma. Delayed intracerebral haematoma was diagnosed from 12 hours to six days after the trauma. The primary CT showed brain contusion in the majority of the patients. The outcome was poor. One patient died and two were severely disabled. The clinical course was more rapid in the two patients with epidural haematoma than in the others. Marked elevation of intracranial pressure was monitored in both cases prior to the second CT examination. In spite of successful evacuation of the haematoma, one patient died and the other developed physical and mental retardation. In one patient a subdural haematoma was diagnosed three months after the trauma. The patient did well postoperatively. PMID- 1462308 TI - [Exchange practice visits--a new and good way of training. A method for quality assurance in general medicine]. AB - The Norwegian Association of General Practitioners has adopted a method for postgraduate education in general practice called exchange practice visit. This article presents the method, which is a simplified version of the procedure described in the booklet, What sort of doctor, from The Royal College of General Practitioners in England. We have tested this way of education, and describe our experiences of it. We conclude that an exchange practice visit is an important supplement to the training of general practitioners, and provides a good tool for quality assurance in medicine. PMID- 1462309 TI - [Aspects of quality assurance and research in general practice]. AB - Research is a prerequisition for setting standards in the field of quality assurance. It is emphasized that scientific work that is intended to have an impact on general practice has to be carried out in general practice. Quality assurance plays a decisive role in recognizing and applying the results of relevant research. The author discusses the significance of typical topics concerning the presentation and prevalence of diseases in general practice. Issues related to quality assurance of scientific studies performed by general practitioners are considered. Intra- and interobserver variation as a problem towards achieving reliable results is described and discussed. The author emphasises the importance of The research council in general practice, as a help in achieving quality assurance. PMID- 1462310 TI - [Quality assurance in a department of pathology and anatomy]. AB - The author describes a quality assurance programme in a department of anatomic pathology. An internal quality assurance committee consisting of four consultants, two chief technicians and a chief secretary meets monthly to decide what measures should be carried out each month. The main activities have been to review random cases of surgical pathology, frozen sections, diagnostic revisions, turn-around times and single event reports. Problems of diagnosis are discussed at a medical staff meeting before they are put before the committee. The programme has been well received in the department. PMID- 1462311 TI - [Should ultrasound examination be performed earlier in pregnancy?]. AB - In 1991 33 perinatal deaths occurred at Rogaland hospital. Seven of the babies showed severely retarded growth (< 3 percentile) compared with the delivery date indicated by ultrasound. Five babies showed moderately retarded growth (from 3-10 percentile) and the remaining babies were not definitely growth retarded. For the three groups the delivery date indicated by ultrasound was on average 18, eight and five days later than the date estimated according to the rule of Naegele. A delivery date estimated by ultrasound at 18-19 weeks may cause serious misjudgements in cases of early retardation of growth. Earlier ultrasound examination is recommended for a more reliable estimated date of delivery. The author discusses ultrasound examination which differentiates estimation of delivery date and screening for malformation. PMID- 1462312 TI - [Curettage in Troms and Finnmark 1980-89. Was it necessary?]. AB - 11,201 dilatations and curettages were performed at four hospitals in the counties of Troms and Finnmark (Northern Norway) during the years 1980-89. The overall rate was 100 per 10,000 women/year. The age distribution and the indications for dilatation and curettage are shown and discussed. Large variations were found during the period, and between the four hospitals. These variations are probably due to differences in the physicians' style of practice. It is concluded that the operation rate is too high, especially in younger women. A further approach to investigations of variations in operation rates is discussed. PMID- 1462313 TI - [Cooperation between regional and central hospitals--how to achieve the best results?]. AB - The authors reviews a recent governmental analysis of cooperation between third line university clinics and local and central hospitals. The hospitals are owned by the government (mainly by the counties), and the various Acts and regulation permit the central authorities to make decisions on all aspects of highly specialized medicine. The analysis concludes that a limited number of problems should be solved by decision of the central government, but only those where national concerns are involved. The counties within a health region should cooperate within a Regional Health Policy Board, to create plans for flow of patients through the health care system, specified for each field of medicine. When such plans have been approved by the Regional Health Policy Board, each county should be willing to accept them. In the event of local disagreement, the central government should decide. PMID- 1462315 TI - [Bicycle accidents]. PMID- 1462314 TI - [A waiting list system for patients for access to the same physician--will be tested in Norway]. PMID- 1462316 TI - [Quality assurance--a balancing act]. PMID- 1462317 TI - [Diagnosis of abuse--without confirming analyses are client's legal rights threatened]. PMID- 1462318 TI - [Quality assurance of drug prescriptions--is it good enough?]. PMID- 1462319 TI - [This is a great country ... quality assurance in Denmark]. PMID- 1462321 TI - [Suicide and mass media]. PMID- 1462320 TI - [Pathology of poverty]. PMID- 1462322 TI - [Laparoscopy in urology]. PMID- 1462323 TI - [Cytokines--from research to clinical use]. PMID- 1462325 TI - [Extirpation of benign renal cysts with laparoscopic technique]. AB - Laparoscopic surgery is rapidly increasing its field of application. We describe the uncomplicated use of peritoneoscopic techniques to remove a benign renal cyst. No previous report of this mini-invasive, patient-friendly and cost effective method has been found in the literature. It should be considered in the rare cases where surgery is indicated as treatment for this benign condition. PMID- 1462324 TI - [Disseminated fungal infections in neonates--risk factors, treatment and course]. AB - During 10 1/2 months in 1990/91 eight premature babies and one mature baby with an intra-abdominal disease had disseminated Candida albicans infections. The incidence in premature newborns was 9% (8/92 patients). Risk factors such as respirator therapy, the use of broad spectrum antibiotics, supplemental parenteral nutrition and central intravascular catheters were frequently seen. Four patients survived the fungal infection. These included three of five babies treated with amphotericin B 0.5 mg/kg/day. Two patients who received fluconazole 3 mg/kg/day died after three days. In one patient the diagnosis was obtained post mortem, and one patient with possible fungemia survived without therapy. The treatment of these patients depends on optimal fungal cultures and good co operation between paediatricians and microbiologists. PMID- 1462326 TI - [Quality assurance of cooperation/distribution of work between primary health care and other health services. Using care for diabetics as a basis]. AB - Chronic illnesses account for an increasing share of the work load of the health services, implying that health personnel have to face a number of different complex problems. Many of these concern co-operation between the various professionals and levels of the health services, and distribution of the load of work. How well this co-operation works will have a decisive effect on the quality of the treatment. These problems are discussed using care of diabetes patients as an example. It is important to achieve medical consensus at different levels. The authors suggest ways of establishing co-operation within the medical profession, specifically defining responsibility, ensuring good and frequent communication with patients, and promoting patient participation. The article also describes concrete solutions and includes a check list for quality assessment. PMID- 1462327 TI - [High quality medical records--high quality medicine]. AB - The medical record is both an indicator of the quality of care, and a means of improving this quality. In addition to being a source of information and a means of communication in the care of patients, the medical record is also becoming a document of increasing legal importance. The content and design of medical records, and how they are kept, should comply with legal requirements. The patients' right to read their own records is well established in Norway. Incomplete records and lack of information will always be held against the doctor in the case of complaints or lawsuits. The medical record provides a good basis for evaluation of care, and a systematic evaluation of medical records, e.g. in groups, is an effective form of medical audit. While the authorities are making an effort to achieve better standardization of medical records, every medical practitioner should do his best to let the everyday use of medical records become an important part of his personal quality assurance. PMID- 1462328 TI - [Quality assurance of medical education--a prerequisite for good medical practice]. AB - Assured quality of medical education is a prerequisite for high quality medicine. Quality assurance of medical education implies a well-planned assessment of the structure, process and outcome of education based on defined standards and objectives, and draws heavily on a thorough knowledge of how people learn. Learning in medicine shares common features at all levels, from undergraduate to continuing education. Three core elements are the context of learning, availability of information, and opportunities for elaboration (educational counselling, mentorship, interaction with peers) as a basis for linking practice and theory. A quality assurance programme must examine all these factors and suggest remedies when appropriate. The upgrading of educational research in medicine, and valuing and recognition of teaching within the profession, are important factors in promoting continuous improvement of the quality of medical education. PMID- 1462329 TI - [Violent behavior of patients--is it predictable?]. AB - In previous research on prediction of violent behaviour in patients some of the most important limitations have been lack of precision in defining violent behaviour, unsystematic registration of violence, and the fact that the prediction has been made valid for contexts other than that in which the original assessment was made. Of the neurobiological factors associated with violence, scientists have recently focused upon the serotonergic system in the central nervous system as being important. The authors review the literature on individual predictors of violent behaviour. Strong predictors seem to be previous violent behaviour, a high degree of hostility, suspiciousness and grandiosity, and current alcohol or drug abuse. The article includes suggestions for future research, and concludes with a presentation of guidelines for clinical assessment of risk of violence, with emphasis on recent events and observed behaviour. PMID- 1462330 TI - [Assessment of habitually violent persons with psychiatric symptoms]. AB - Persons with habitual violent behaviour are categorized according to their motivation, psychiatric illness and/or personality disorder. Assessments of the different types of violence are essential for placement and safe handling of potentially violent persons in acute threatening situations, and for planning treatment. PMID- 1462331 TI - [Social network, alcohol drinking habits and injuries caused by violence among women and men in the county of Akershus. Results from anonymous questionnaires among persons aged 40-42 years. 1990-91]. AB - All residents aged 40-42 in Akershus county were invited to screening for cardiovascular risk factors in 1990-91 as part of a prevention programme. Of the 13,607 attendants, 8,960 answered an anonymous questionnaire about social network, drinking habits, and injuries due to violence. Compared with data from the Central Bureau of Statistics, our material included a high percentage of persons with a higher education, a high percentage of married persons, and a low percentage of persons living alone. Results in respect of social network and drinking habits roughly agreed with those of other studies. Of the males, 15.7% had been injured at least once as a result of violence, most often assault and robbery. Of the females, the corresponding percentage was 18.1. Here the dominating forms of violence were maltreatment, threats and sexual assault. Females were more often exposed than males to repeated violence and more often suffered persisting problems as a result of maltreatment. Compared with other studies, we found a high prevalence of injuries from violence among females, suggesting underreporting of experiences of violence by females in studies based on personal interview or the hospitals' injury register. PMID- 1462332 TI - [Do physicians not examine patients with back pain?]. PMID- 1462333 TI - [Surgical gloves can cause severe problems]. PMID- 1462334 TI - [Centralization of obstetrical care and perinatal mortality in Norwegian counties during the period 1986-90]. PMID- 1462335 TI - [Euthanasia]. PMID- 1462336 TI - [Medical education out of date]. PMID- 1462337 TI - [Physicians' practice in connection with declaration of fitness]. PMID- 1462338 TI - [Is quality assurance integrated in basic medical education?]. PMID- 1462339 TI - [Medical leadership at sectioned departments]. PMID- 1462340 TI - [Supplementary hay reduces fur chewing in rabbits]. AB - We tested the hypothesis that loose grass hay as a supplement to a pelleted diet reduces fur chewing in rabbits. Weanling rabbits (n = 315) were given one of three diets ad libitum: a control, pelleted diet, the pelleted diet containing 20% (wt/wt) hay meal or the pelleted diet plus loose hay. Fur chewing was assessed indirectly by blind scoring of the extent of alopecia in live rabbits and the amount of gastric hair after slaughter. Rabbits given either loose hay or the diet pellets containing hay displayed significantly less alopecia on the back and sides than control rabbits did. Loose hay, but not the pellets containing hay, completely prevented the development of alopecia on the forehead. The provision of loose hay as supplement to the control diet pellets significantly reduced the amount of gastric hair, whereas inclusion of hay meal into the pellets had no effect. It is concluded that supplemental loose hay prevents rabbits from pulling off fur from the forehead of cage mates. This effect of hay might be related to satisfaction of a craving for nibbling. PMID- 1462341 TI - [Diarrhea in cats]. AB - Diarrhoea is regarded as the characteristic symptom of intestinal disturbances. However, cats with intestinal disturbances can also show other symptoms such as vomiting, increased or decreased appetite and loss of weight. Cats with diarrhoea are usually only referred to the clinic if they have a chronic problem. Acute diarrhoea reacts well to symptomatic treatment, but chronic diarrhoea requires a specific diagnosis for a directed therapy and prognosis. It is essential to examine faeces and blood when evaluating a cat with diarrhoea. In contrast to the situation for dogs, there are no good specific digestion and absorption tests available for cats to evaluate pancreatic and intestinal function. Exocrine pancreatic insufficiency rarely occurs in cats. A preliminary diagnosis of small intestine disorders can be made on the basis of the faeces staining positive for fat, an oral fat absorption test and the response to therapy. The definitive diagnosis must usually await the results of histological examination of intestinal biopsy samples. Cats with acute diarrhoea often recover spontaneously, and symptomatic treatment is only necessary for severe cases. A specific diagnosis is needed for cats with chronic diarrhoea, to enable directed treatment. Corticosteroids are used in the treatment of chronic enteritis because of their immunosuppressive and anti-inflammatory actions. Antibiotics are only indicated for specific bacterial infections (such as Salmonella and Campylobacter), bloody diarrhoea, or rampant bacterial growth. Specially formulated diets play a major role in the treatment of both acute and chronic diarrhoea. PMID- 1462342 TI - [Professional practice and health status of veterinarians]. AB - By carrying out an inquiry by mail to 925 veterinarians in the Southern Netherlands, there was looked after a relationship between the professional practice of the veterinarian and his health status. The inquiry was completed and returned by 453 veterinarians. The questions about the health status dealt with complaints about: the respiratory tract, the stand and motion apparatus and the hearing. Based on over 75% of the work package the veterinarians were divided into: veterinarians in the large animal practice, veterinarians in the small animal practice and veterinarians with an other job. The results are compared with the results of a comparable inquiry by pig farmers. Veterinarians, who do smoke, have twice as much respiratory complaints than no smoking veterinarians. Veterinarians in the large animal practice have more respiratory complaints, more complaints about elbows and wrists and more deafness. Veterinarians in the small animal practice have more complaints about allergies, and more complaints about the back and the knees and feet. PMID- 1462343 TI - [Role of the veterinarian in changing animal husbandry]. PMID- 1462344 TI - [Causes of primary and secondary glaucoma in dogs]. PMID- 1462345 TI - [Acute mortality in pigs caused by Streptococcus suis type 1]. AB - In early 1991 many young pigs died without clinical signs on a farm in the Province of Utrecht. This article describes the isolation of Streptococcus suis type 1 after postmortem examination of the piglets. PMID- 1462346 TI - [Taxus baccata poisoning in lambs and meat inspection]. AB - Yew (Taxus baccata) poisoning in lambs: meat control twenty-two poisoned lambs were slaughtered at a special slaughterhouse. Yew intoxication was diagnosed on the basis of the anamnesis and the presence of yew needles in the rumen. Data from the literature concerning the toxicity of yew and some (traditional) uses of yew are reported. The symptoms and post-mortem findings in animals and humans are discussed, together with the poorly effective treatment of yew poisoning and preventative measures. The outcome of the meat inspection is explained on the basis of current and new regulations (Regulations and Guidelines Governing the Inspection of Meat 91/497/EEG). A reliable and recognized method for the detection of taxins is required. PMID- 1462347 TI - [Pannus]. PMID- 1462348 TI - [Euthanasia in domestic animals]. PMID- 1462349 TI - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin or 2,2',4,4',5,5' hexachlorobiphenyl on vitamin K-dependent blood coagulation in female germfree WAG/Rij-rats. AB - Newborn infants are susceptible to bleeding disorders caused by a vitamin K deficiency, so called 'haemorrhagic disease of the newborn' (HDN). These bleedings often occur in infants after medication of the mother with antiepileptics, such as phenobarbital or phenytoin. It has been suggested that an increase in the late type of HDN in exclusively breast-fed infants might be related to the presence of cytochrome P450-inducing polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in human milk. In order to study this possible mechanistic relationship 5-week-old, germfree, female WAG/Rij-rats were exposed to a single oral dose of either 1 microgram 2,3,7,8-tetrachlorodibenzo-p-dioxin/kg body weight (TCDD) or 30 mg 2,2',4,4',5,5' hexachlorobiphenyl/kg body weight (HxCB), representing cytochrome P-450 1A (3 methylcholanthrene type) and 2B (phenobarbital type) inducers. During the experiment blood coagulation time from each rat was measured. Also, hepatic 7 ethoxy-(EROD) and 7-pentoxyresorufin O-dealkylating (PROD) activities and total cytochrome P450 content were measured. Blood coagulation time (Thrombotest) in the HxCB-treated rats was significantly prolonged and positively correlated to PROD activity and total P450 content. No clear effect of TCDD on coagulation time could be observed under these experimental conditions. These results suggest involvement of P450 2B isoenzymes in vitamin K metabolism. PMID- 1462350 TI - Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats. AB - Aniline and its halogenated derivatives are widely used as chemical intermediates. The purpose of this study was to determine the hepatotoxic and nephrotoxic potential of the 2-haloanilines. Male Fischer 344 rats (n > or = 4) were injected (i.p.) with 1.0 or 1.25 mmol/kg of: aniline (A), 2-fluoroaniline (2 FA), 2-chloroaniline (2-ClA), 2-bromoaniline (2-BrA), 2-iodoaniline (2-IA) or vehicle (0.9% saline, 2.5 ml/kg). All compounds were injected as hydrochloride salts. Renal and hepatic function was monitored 24 h after treatment. All of the 2-haloanilines induced oliguria, diminished kidney weight, tubular casts and decreased renal cortical slice accumulation of organic anions. Blood urea nitrogen (BUN) levels were increased (P < 0.05) by treatment with 1.0 or 1.25 mmol/kg of 2-FA, 2-ClA or 2-BrA. Hepatic alterations were also observed and characterized by elevated plasma ALT/GPT activity and altered morphology in the centrilobular region. The nephrotoxic and hepatotoxic potentials were similar among the 2-haloanilines but aniline was less toxic than its 2-halo derivatives. These results demonstrated that halogen substitution at the 2-position of aniline increased hepatic and renal toxicity. However, the severity of toxicity was not influenced by the nature of the halogen substituent. PMID- 1462351 TI - Interaction of cadmium with atrial natriuretic peptide receptors: implications for toxicity. AB - Atrial natriuretic peptide (ANP) is a diuretic and vascular smooth muscle relaxant which plays a pivotal role in cardiovascular regulation. Since cadmium (Cd) produces cardiovascular toxicity and alters ANP levels in atria and hypothalamus, its effect on ANP receptors were studied in rats and in PC12 cells exposed to Cd. Male rats were injected with CdCl2 (0.01, 0.1, 0.5 or 1.0 mg/kg, i.p.) twice a day for 7 days and then maintained for a period of 30 days. On experimental day 37 ANP receptor binding in the adrenal cortex, aorta and kidney cortex was studied by saturation isotherm analysis. In Cd-treated animals a non dose related decrease in receptor affinity and density was observed in the kidney and aorta with the aortic ANP receptors being the most sensitive. Cellular regulation of the receptor was studied in PC12 cells, a cell line that expresses functional ANP receptors. Incubation of PC12 cells with Cd reduced both the affinity of the receptor for ANP and decreased the number of binding sites on the cell plasma membrane. The ratio of ligand-receptor complex internalized in the cell to ligand bound to the plasma membrane was significantly decreased following Cd pretreatment (500 microM). A significant decrease in the internalization rate of [125I]ANP was observed in cells incubated concurrently with Cd and ligand. In photoaffinity labelling studies with [125I]ANP, binding of ANP to B and C receptors subtypes was decreased following treatment of either intact cells or plasma membranes with Cd. It was concluded that Cd produces significant alterations in the ANP receptor, both in in vitro and in vivo models and it is proposed these effects play a role in the cardiovascular toxicity of this heavy metal. PMID- 1462352 TI - Effect of cigarette smoking on salivary epidermal growth factor (EGF) and EGF receptor in human buccal mucosa. AB - The mouth acts as a primary target for cigarette smoke which is associated with several oral diseases and cancer. The present study investigated the effect of cigarette smoking on salivary EGF and the buccal EGF receptor. Samples of whole saliva and buccal biopsy were obtained from 15 healthy volunteers (10 smokers and 5 non-smokers). The smokers smoked 20 or more cigarettes/day for more than 5 years. Salivary cotinine (a major metabolite of nicotine) was determined by radioimmunoassay (RIA). The salivary cotinine level was consistent with the self reported smoking status (smokers, 106-530 ng/ml saliva; non-smokers, < 2 ng/ml saliva). As compared to the non-smokers, the salivary EGF concentration (determined by RIA) was 32% lower in those smokers whose salivary cotinine level was 250 ng/ml or higher (non-smokers, 2.21 +/- 0.16; smokers, 1.57 +/- 0.09 ng/ml saliva; mean +/- S.E.M., P < 0.01). There was no significant difference in 125I labeled EGF binding to the buccal receptor between the two groups. However, EGF stimulated the autophosphorylation of a 170-kDa protein band in the sample of non smokers, but not in the smokers. The immunoblot analysis using anti-EGF receptor antibody indicated that the smoking-related deficiency in EGF receptor autophosphorylation was due to the functional alteration of the receptor proteins. In conclusion, cigarette smoking reduces the salivary EGF level and impairs the function of buccal EGF receptor, which may be associated with the pathology of smoking-related oral disease. PMID- 1462353 TI - Further studies on the hematopoietic damage produced by a single dose of T-2 toxin in mice. AB - Previous studies revealed that a single dose of T-2 toxin produces a strong inhibition of the 59Fe incorporation into circulating erythrocytes in mice. In the present work it is shown that equivalent doses of T-2 toxin (0.30 mg/kg and above) can produce a relative depletion of granulocyte-macrophage colony-forming cells (CFU-GM) in the bone marrow of treated mice. In additional experiments, both the 59Fe uptake into erythrocytes and the bone marrow CFU-GM were measured as a function of dose and time after a single administration of T-2 toxin. It was found that the initial inhibitory effects are reverted between 24 h and 72 h and that in some cases there is even a significant increase over the normal values, indicating that there may be a compensatory activation of the hematopoietic system. The results presented here suggest that extremely small doses of T-2 toxin can produce a significant degree of bone marrow cytotoxicity and therefore even low level dietary contamination may be of concern. PMID- 1462354 TI - The role of metabolism in carbon tetrachloride-mediated immunosuppression. In vitro studies. AB - In vitro studies were performed to determine the role of metabolic bioactivation in mediating immunosuppression by CCl4. Direct addition of CCl4 to naive spleen cell cultures sensitized with either sheep erythrocytes, DNP-Ficoll or lipopolysaccharide (LPS) resulted in a marked inhibition of the antibody forming cell (AFC) response to all three of the selected antigens at 3.0 mM concentration in culture. However, this inhibition was primarily due to the direct cytotoxic effects of CCl4 on spleen cells following 3-5 days of culture in the presence of the chemical as evidenced by a decrease in cell number and viability and by the absence of selective effects on T-cell dependent humoral responses which is contradictory to the effects observed in vivo. Co-incubation of splenocytes for 1 h with primary hepatocytes, but not with subcellular metabolic activation systems, such as S9 or microsomes, enhanced the immunotoxic effects of CCl4 in vitro. Interestingly, a 3-h co-incubation of spleen cells with metabolically active hepatocytes in primary culture resulted in an even greater potentiation of the immunotoxic effects of CCl4 as determined by the T-cell dependent IgM AFC response. Conversely, under identical conditions, CCl4 did not suppress humoral responses to the polyclonal B-cell activator LPS which is in agreement with the effects produced by in vivo exposure to CCl4. It is important to emphasize that for the metabolic activation studies (i.e. co-incubation with either S9, microsomes or hepatocytes), spleen cells were washed free of CCl4 immediately following the co-incubation period. Control splenocyte cultures (i.e. no metabolic activation system) incubated in the presence of CCl4 alone at 3.0 mM over a 3-h time-period, had no effect on spleen cell function, number or viability. In agreement with our previous findings which indicate that pretreatment of mice with inducers and inhibitors of the mixed function oxygenase system prior to CCl4 administration modulated the immunotoxic effects of CCl4 in vivo, these results lead us to conclude that immunotoxicity by CCl4 requires metabolic activation. PMID- 1462355 TI - Reduced Leydig cell volume and function in adult rats exposed to 2,3,7,8 tetrachlorodibenzo-p-dioxin without a significant effect on spermatogenesis. AB - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to alter testicular function. However, its effect on the efficiency of spermatogenesis or on Leydig cell volume has not been determined in adult rats. In two replicas, adult male rats received a single intraperitoneal injection of TCDD at a rate of 0, 12.5, 25.0, or 50.0 micrograms/kg body weight. Rats were sacrificed 4 weeks after treatment. The cytosolic Ah receptor in the testis was estimated at 10.3 +/ 1.2 fmol/mg protein in these adult rats. The presence of the Ah receptor at this concentration in the testis reveals that the testis is a possible target organ for TCDD-induced responses. Left testes were homogenized and testicular spermatids were counted by phase contrast cytometry to determine daily sperm production. Right testes were vascularly perfused with glutaraldehyde, embedded in Epon 812, sectioned at 0.5 micron, stained with toluidine blue and evaluated by stereology for germ cells or Leydig cells. Body weight was reduced (P < 0.01) in a dose-dependent fashion. Testicular weight and daily sperm production per testis were not significantly reduced by TCDD. Androgen receptor concentrations in the testis and prostate were not affected. Weights of two androgen-sensitive organs (seminal vesicles and epididymis) were reduced (P < 0.01) in a dose dependent fashion and serum concentrations of testosterone were reduced in a dose dependent fashion in Replica 2. Due to low numbers of animals in Replica 1, the reduced Leydig cell volume was not significant after TCDD treatment; however, in Replica 2 there was a dose-dependent reduction (P < 0.01) in volume per testis of Leydig cell cytoplasm, nuclei, or total Leydig cell volume. Production of testosterone was sufficient to maintain spermatogenesis quantitatively; however, TCDD caused a dose-dependent reduction in Leydig cell function and Leydig cell volume per testis. This study showed for the first time that TCDD-induced androgen deficiency of male rats may be explained by the loss of total volume of Leydig cell cytoplasm. This study also further illustrates the reserve capacity of Leydig cell function to maintain spermatogenesis when the volume of these cells is significantly reduced. PMID- 1462357 TI - Interaction of monocrotophos and its novel thion analogues with microsomal cytochrome P-450: in vivo and in vitro studies in rat. AB - The binding of monocrotophos (MCP) and its two thion analogues (coded as RPR-II and RPR-V) to rat hepatic microsomal cytochrome P-450 (HMC) were investigated in vitro by difference spectroscopy. These three organophosphorus insecticides were found to bind stoichiometrically to HMC with very high affinity (Ks 34-50 microM). RPR-V showed the highest binding affinity followed by RPR-II and MCP. Association of these compounds with HMC occurred within 2 min of addition in the cuvette and therefore, appeared to be tight binding ligands of cytochrome P-450. In vivo studies at equitoxic doses of the three compounds 24 h after oral treatment in rats revealed that they all caused reduction in MC content in liver, lung, kidney and brain, as against induction in cardiac and splenic cytochrome P 450. These in vivo results suggest organ specificity in modulating the microsomal cytochrome P-450 (MC) content of hepatic and extra-hepatic tissues by the three compounds. Apparently, their binding affinity with HMC is strongly correlated with their LD50 value and has a substantial co-relationship with the cytochrome P 450 level in the liver. PMID- 1462356 TI - Assessment of exposure to parenteral and oral aluminum with and without citrate using a desferrioxamine test in rats. AB - The primary purpose of this study was to determine the relative usefulness of various measures to monitor body aluminum burden in weanling rats fed various amounts of aluminum (0.39 mumol Al/g diet for 29 days, approximately 40 mumol Al/g diet with or without citrate for 29 days and approximately 100 mumol Al/g diet with citrate for 12 or 29 days) or injected intraperitoneally with graded doses of aluminum (0.01, 4.6, 11.8, 23.5 or 94 mumol Al). Twenty-four hours prior to sacrifice, all rats were injected intraperitoneally with either desferrioxamine (75 mg DFO) or buffer. All seven indices of aluminum exposure monitored (i.e. tibia, liver, kidney and serum aluminum concentrations; changes in serum aluminum concentrations in response to DFO; urinary aluminum excretion with and without DFO treatment) were highly (P < 0.001) correlated to parenteral aluminum exposure. Five of these measures (i.e. tibia, liver and serum aluminum concentrations and urinary aluminum excretion with and without DFO treatment) were also highly (P < 0.001) correlated to oral aluminum loads. Changes induced by DFO were very small. Moreover, the 'DFO stimulated' serum and urine aluminum concentrations were not more correlated to the body load of aluminum, as indicated by tibia aluminum concentrations, than baseline values. Comparisons of aluminum exposure in tibias and sera of rats exposed to parenteral and oral aluminum indicated that only 0.01-0.04% of dietary aluminum was absorbed. Ingestion of citrate had small but significant effects on aluminum retention. PMID- 1462358 TI - Localization and health effects of lanthanum chloride instilled intratracheally into rats. AB - Lanthanum (La) is one of the rare earths used in diverse high technology fields for which sufficient data for assessing its health effects have been lacking. The biological effects and metabolic behaviors of La were studied by instilling lanthanum chloride intratracheally into male Wistar rats. The distribution of La among tissues revealed that the metal remains mostly in the lung with a biological half-time of 244 days. The subcellular localization by transmission electron microscopy with an X-ray microanalyzer indicated that La localizes in macrophages as high electron-dense granular inclusions in lysosomes and on the cell surface and basement membranes of type I pneumocytes among lung cells. The pulmonary health effects were examined by biological indices of the bronchoalveolar lavage fluid (BALF) and lung tissue. The acute toxicity estimated by lactate dehydrogenase activity in BALF was comparable to those of yttrium and copper that had been determined under the same protocol. Microscopic examination of the lung indicated a characteristic increase in the number of eosinophils. PMID- 1462359 TI - Poly(ADP-ribose)polymerase-activity of chicken embryo cells exposed to nucleotoxic agents. AB - Poly(ADP-ribose)polymerase (PARP)-activity was assessed in vitro from the incorporation of the adenosine-diphosphate-ribose moiety of 14C-NAD+ in the acid insoluble cell fraction. When compared to mammalian (rat) cells, chicken embryo cells exhibit an almost three- to fourfold higher constitutive PARP-activity and an about two- to threefold lower chromatin compactness as evidenced by viscometry of alkaline cell lysates and nucleoid sedimentation. X-irradiation, bleomycin and H2O2 activated PARP. Hyperthermia (43 degrees C), doxorubicin, ethidium bromide and novobiocin resulted in an inhibition of the enzyme activity. Even at the highest doses used, UV-light, monofunctionally alkylating agents and the bisbenzimide Hoechst 33258 remained without significant effects. It is suggested that, with respect to DNA-and/or chromatin-interactive agents, the chicken embryo PARP-test may be complementary to the results of morphological and biochemical studies. PMID- 1462360 TI - Reptilian thymus gland: an ultrastructural overview. AB - Like in higher vertebrates, the thymus gland of reptiles consists of lymphoid cells within epithelial framework and characteristic myoid cells. Mammalian-like Hassall's corpuscles are absent. Secretory cells, secretory and degenerative cysts as well as phagocytic cells, and plasma cells can be observed. Interdigitating cells and some characteristic features of thymic innervation and vascular system are also described in the reptilian thymus gland. PMID- 1462361 TI - Effects of cyclosporin A on mouse thymus: immunochemical and ultrastructural studies. AB - The in vivo effect of cyclosporin A (CsA) on the murine thymus was investigated by studying the ultrastructural cellular alterations, which are described for the first time, and the immunohistochemical modifications of thymocytes and thymic reticulo-epithelial cells (TREC). A marked reduction of the thymus size became apparent after 6 days of CsA treatment (10 mg/kg/day). Light microscopy studies using polyclonal antibodies (Ab) or monoclonal Ab specific to lymphoid sub populations (anti-CD4, anti-CD5, anti-CD8), and specific to epithelial cells (anti-keratin: AKs, K8), to cortical TREC (TR4) and to subcapsular/medullary TREC (TR5, 3H9) showed that the number of CD4- 8+ or CD4+ 8- medullary thymocytes dramatically decreased and that the cortical TREC are affected, after 10 days of CsA treatment. These observations were confirmed by electron microscopy studies demonstrated that the medullary lymphoid population disappeared almost entirely. TREC, principally cortical type, presented signs of cellular lysis. A few cortical thymocytes showed some damage. At day 8 the medullary thymic tissue was disorganized, but no change was noted in the subcapsular area right up to the final day (day 10) of CsA treatment. These results suggest that CsA has a harmful effect on cortical TREC, which affects the development of immature thymocytes. PMID- 1462362 TI - Interdigitating cells in the rat thymus during cyclosporin A treatment: ultrastructural observations. AB - Major Histocompatibility Complex (MHC) class II-positive cells are almost completely absent in the rat thymic medulla after cyclosporin A (CsA) exposure. This phenomenon has been related to alterations in the medullary interdigitating cells (IDCs), representing either down-modulation of RT1 class II antigen on persistent IDCs, or actual disappearance of IDCs. To resolve this issue, we performed an ultrastructural study of the rat thymic medulla during CsA treatment (15 mg/kg body weight/day CsA subcutaneously for 7 to 14 days). At day 7 after exposure, only very few IDCs could be identified. They showed an abnormal ultrastructural morphology as judged by inconspicuous membrane interdigitations and lack of Birbeck granules. At day 14, the number of IDCs was larger. At this time, the IDCs had a normal ultrastructure, except for the almost complete absence of Birbeck granules. We conclude that CsA causes an initial depletion of IDCs from the thymic medulla. The ultrastructural morphology of the few IDCs present suggests an immature character. New IDC immigrants appear in the medullary area already during CsA treatment, indicating early recovery. PMID- 1462363 TI - [Hydrophobic interactions of serine proteases with low molecular weight compounds: partial effector displacement from the activated enzyme by the substrate]. AB - 1,2,3-tris-tri-beta-phenylethylaminopropane (a compound which can simultaneously interact with S1- and S2'-enzyme sites and has complicated grouping in the region analogous to "leaving group" of a substrate) has been studied for the effect on chymotriptic hydrolysis. Anomalously high inhibitory effect of some cumbersome organic compounds is explained on the base of the obtained data. PMID- 1462364 TI - [Postradiation changes in Ca2+-ATPase and Mg2+-ATPase in thymocyte plasma membranes]. AB - The rats were irradiated in the doses 1, 5, 4, 7 and 10 Gr and on the 1, 8, 15, 22 and 30 day after the irradiation activity of Ca(2+)-ATPase and Mg(2+)-ATPase and peroxidation lipids in the thymocytes was determined. It was found that postradiation changes in activity of Mg(2+)-ATPase were characterized by a higher sensitivity to the processes of lipids peroxidation as compared to Ca(2+)-ATPase. PMID- 1462365 TI - [Thermoregulatory uncoupling of oxidation and phosphorylation in the chick brain in embryogenesis]. AB - The cooling of hen incubated eggs to 28 degrees C brings to disconnection of oxidative phosphorylation in brain on the 12th day of development. The addition of DNP (5 x 10(-5) M) takes off the cooling effect. PMID- 1462366 TI - [Effect of compounds having hypotensive activity on microviscosity of phospholipids membranes]. AB - Vincapane, apressin, raunatin, reserpine and prazosin have been studied for their effect on the state of microviscosity of phospholipid bilayers from lecithin and cardiolipine. The method of fluorescent probing using pyrene and asymmetrical polymethine dye 4501 u have been used for this study. Character of changes of phospholipid bilayers microviscosity as affected by these compounds depends on their concentration in the solution. Vincapan lowers microviscosity of membranes from lecithin in the interval of the concentrations given. Advantages of fluorescent probing by means of asymmetric polymethine dye in comparison with pyrene were shown. PMID- 1462367 TI - [Effect of brain cytosol proteins of embryonal and adult animals on RNA polymerase activity of isolated brain nuclei]. AB - Cytosol and its fractions obtained by the precipitation with ammonium sulphate and ion-exchange chromatography have been studied for their effect on the RNA polymerase activity of isolated nuclei. We observed the discrepancies in the action of total cytosol of embryonal, newborn or adult animals on the label's incorporation in RNA. It was found that some fractions increased DNA-polymerase activity of isolated nuclei in cattle embryonal cytosol. The same fractions obtained from adult cytosol did not act in such a way. It was found that most fractions obtained from cytosol of adult brain inhibited the RNA-polymerase activity of brain nuclei. PMID- 1462368 TI - [Influence of delta-sleep-inducing peptide on the activity of proteolytic enzymes in the rat brain under hypokinesia]. AB - Single administration of the delta-sleep-inducing peptide (DSIP) in a dose of 12 micrograms/100 g to intact animals makes the activity of neutral proteinases and cathepsin D higher in the rat brain and blood serum. Hypokinesia of different duration changes activity of neutral and acidic proteinases and induces accessibility of cathepsin D to the cytosol as a result of damage in lysosomal membrane. Injection DSIP induces a decrease A/B of cathepsin D to the control level under 1-h hypokinesia condition and normalizes the neutral proteolytic activity under 6-h hypokinesia condition. PMID- 1462369 TI - [Pyruvate decarboxylase inactivation by interaction with substrate and molecular oxygen]. AB - Pyruvate may promote the yeast pyruvate decarboxylase inactivation when affected by molecular oxygen. In the presence of pyruvate and O2 inactivation of enzyme increases with the initial substrate concentration increasing. pH-dependence of pyruvate decarboxylase inactivation under joint action of substrate and O2 has maximum in the region 6.9-7.5. It is suggested that the influence of pyruvate and molecular oxygen is connected with the coenzyme-substrate complex oxidation in an active site of yeast pyruvate decarboxylase on the steps preceding the release of free acetaldehyde. PMID- 1462370 TI - [Isolation of lectin from horse chestnut (Aesculus hippocastanum L.) seeds and study of its interaction with carbohydrates and glycoproteins]. AB - The lectin from horse chestnut seeds was obtained by affinity chromatography on a sorbent prepared from the egg white, 95 mg of lectin per 1 kg of fresh seeds being obtained. Molecular weight was determined by gel-filtration on tojopearl HW 55 and it composed 132 kDa. SDS-polyacrylamide gel electrophoresis revealed the presence of one component with molecular weight of 33 kDa. One band has been revealed by means of disc-electrophoresis in acidic (pH 4.5) and alkaline system (pH 8.9). Sugar was not detected in the lectin. Amino acid composition of the lectin has been determined. The lectin agglutinated horse erythrocytes in minimal concentration of 9.5 ngml, to the less extent rabbit (4.9 mkg/ml), rat (62 mkg/ml), human (73 mkg/ml), but did not agglutinate erythrocytes of a sheep and cow. Purified lectin did not interact with monosaccharides, but interacted with O glycans. PMID- 1462371 TI - [Effect of a single and fractionated gamma-irradiation on lipid content in rat blood and tissues]. AB - Contents of lipids, character of blood plasma chemiluminescence and separate classes of lipoproteins as well as the content of the lipids of tissues under single and fractionated gamma-irradiation of rats in a dose of 3 Gr. The development of hyperlipidemia and hypercholesterolemia for four weeks after irradiation which are more expressed under a single irradiation, a decrease of total content of cholesterol and triglycerides in the heart and liver tissues to the end of the experiment 24 hour after irradiation are registered in the both groups of animals. PMID- 1462373 TI - [Electrolyte composition of cow and calf tissues in health and in acute digestive disturbances]. AB - Sodium, potassium, calcium, magnesium, manganese, zinc and chloride contents in the blood plasma of calves at parturition have been established to correspond to their levels in blood of cows during their calving period. Iron and inorganic phosphorus contents in calves blood plasma appeared to increase and copper content to be lower in this period as compared to postnatal period. By the third day of postnatal ontogenesis sodium concentration in calves blood decreased, copper level increased and the rest indices of water-salts metabolism in calves and adult animals were alike. Digestion disturbances in the calves were accompanied by changes in levels and magnitude of Na+/K+ ratio, magnesium, iron, copper, manganese and zinc contents in blood, liver and kidneys as well as Ca++/Pi ratio in mitochondria and cytosol of liver and jejunum mucose layer cells in comparison with clinically healthy animals. PMID- 1462372 TI - [Comparative characterization of the lipoprotein spectrum and status of free radical processes in the blood of rabbits exposed to external gamma-irradiation and cholesterol administration]. AB - Characteristic of lipoprotein spectrum and state of free-radical processes in the animals under action of ionizing radiation and cholesterin diet are comparatively studied. The content of lipids in the blood serum increases on the 5th day after irradiation and then decreases on the 15th and 30th days. Cholesterin diet increases the content of cholesterin under practically unchanged content of triglycerides in the blood serum in all the terms of investigations. Total decrease of the intensity of induced chemiluminescence of the blood serum and erythrocytes after irradiation is shown. Peroral introduction of cholesterin evokes differently directed changes in the light sum of chemiluminescence--a decrease in erythrocytes and increase in the blood serum. PMID- 1462374 TI - [Effect of hyperglycemia and hyperthermia on liver mitochondrial respiration and blood glucose content of rats during postnatal ontogenesis]. AB - Correlation between glucose level in blood and liver mitochondrial energetics of 1, 10, 20-days rats under hyperglycemia and high environmental temperature (38 degrees C) has been studied. Glucose feeding led to a significant increase of glucose content in blood, this increase being less at hyperthermia. Glucose feeding strengthened the oxidation of such intermediates as succinate (Krebs cycle), pyruvate and malate (hydrocarbonates) and caprylate (lipid). High environmental temperature with hyperglycemia suppresses the liver mitochondria breathing, hydrocarbon and lipid intermediates being used; the suppression is less in the presence of succinate. It is found that liver mitochondria of growing rats at different experimental conditions oxidize different intermediates with various rates. These data can be explained in the light of ontogenetic evolution of the energetic apparatus. It is supposed that exogenic glucose is the factor which activates growing processes of animals and to certain extent diminishes the negative influence of hyperthermia on the organism. PMID- 1462375 TI - [Antioxidant properties of oxy- and metmyoglobin]. AB - Lipid peroxide formation is inhibited by met- and oxymyoglobin. Oxymyoglobin as higher antioxidant activity than metmyoglobin. Oxymyoglobin has higher antioxidants activity in concentration of 800 ng/ml than metmyoglobin by 38.6%. PMID- 1462376 TI - [Change in the structural state of fractionated liver chromatin in E vitamin deficiency]. AB - Structural modification of transcriptionally active and repressed rat liver chromatin fractions at antioxidant insufficiency caused by E-avitaminosis, was shown. This modification consisted in the compactization of the first fraction structure and in the relaxation of the second one. Besides, compactization of the active fraction structure was accompanied with the increase of fluidity of the lipid bilayer. On the whole antioxidant insufficiency caused more expressed structural changes in the active chromatin fraction, this correlated with the intensity of lipid peroxidation reactions in the fractions. PMID- 1462378 TI - [Effect of chelators of bivalent metal ions on the reaction of myometrium actomoysin superprecipitation]. AB - Kinetic regularities of the reaction of superprecipitation of myometrium actomyosin, as well as the effect of different concentrations of EGTA, EDTA and diphosphonic acids on this process have been studied. Results obtained are of interest from the viewpoint of possible practical use of diphosphonates as factors modifying interaction of the contractile proteins of the uterus smooth muscles under the pathology of contractile response. PMID- 1462377 TI - [Changes in the structure and reactions of lipid peroxidation of liver chromatin as affected by 0,0-dimethyl-0,2,2-dichlorovinylphosphate]. AB - Intoxication of rats by 0,0-dimethyl-0-2,2-dichlorovinylphosphate (DDVPh) leads to marked biochemical changes of transcriptionally active (TACh) and repressed (RCh) liver chromatin fractions. These changes are connected with structural relaxation of the fractions, which is manifested by the increase of intensity of protein self-fluorescence. Free radical nature of these changes was supposed, which was proved by the modification of LPO reactions in the both chromatin fractions under the influence of the pesticide concerned. PMID- 1462379 TI - [Humoral factors of transplantation immunity in carp]. AB - The levels of isohemagglutinins, isohemolysins, heterohemagglutinins and lysozyme in blood serum of one and half year old carps have been fixed after scales transplantation. Since three weeks after grafting isohemagglutinins and isohemolysins were revealed in recipient fishes with the prevalence of 25% and 95% respectively. Intact carps from the same group were lack of these antibodies. Recipient and intact fishes did not differ reliably by heterohemagglutinins and lysozyme level in the blood serum. There was no correlation between destroyed allografts share and hemolysins titre of serum, so the double role of humoral antibodies in grafting immunity in carps can be assumed. PMID- 1462380 TI - [Accidental falls among the elderly--can anything be done for this problem?]. PMID- 1462381 TI - [Accidental falls in nursing homes. A study of the extent and circumstances of accidental falls in nursing homes]. AB - Accidental falls in 54 nursing homes with 2228 elderly residents aged 65 years and over were registered during a period of seven months. During the seven months, 512 of the elderly residents fell on a total of 934 occasions. Forty-two fractures of the neck of the femur occurred. The risk of falls for elderly residents of nursing homes is very high, but the majority of falls do not result in permanent damage. In this investigation, no differences could be demonstrated between staff groups or circumstances concerning falls with and without resultant damage. All falls should be regarded as warnings and result in detailed investigation of the circumstances of the fall in view of prophylactic measures. Accidental falls are caused by a complex interaction between a series of health, therapy, furnishing and attitudes. Various circumstances are emphasized in this investigation which are connected with an increased risk of falling, e.g. vertigo, problems of balance, certain aids and activities in connection with toileting. PMID- 1462382 TI - [Accidental falls in nursing homes. A study on the role of drugs in accidental falls in nursing homes]. AB - The drug consumptions of 2228 residents in nursing homes aged 65 years and over were investigated and related to accidental falls during a period of seven months. 95% of the residents received treatment with one or more drugs and 33% with six or more drugs. The risk of accidental falls was significantly increased in persons receiving hypnotics, psychomarmaca and anti-Parkinson medicine. Individuals receiving diuretics, particularly thiazides, were less at risk for accidental falls. This investigation revealed an increased risk of falls particularly when residents were receiving treatment with a short-term hypnotic (Triazolam). It is recommended that this finding should be investigated further. PMID- 1462383 TI - [Physical causes of accidental falls among the elderly in their own homes]. AB - Accidental falls in elderly persons involve considerable illness and great hospital costs. During the period 1971-1986, the incidence has risen from 14 to 19 per 1000 annually. Four hundred and seventy-three individuals aged 60 years or more who had fallen in their own homes and who sought help in Odense Hospital after the accident were interviewed consecutively. The replies to these interviews described the circumstances involved in the fall together with the health and social conditions. Women constituted 78% of the material with preponderance of people living alone as compared with the background population. Just under half of the patients had had a previous fall. Fractures were sustained in 40% of the cases. In 51% of the cases, a definite or probable external circumstance was the cause of the fall. In 150 out of 237 accidental falls, caused by external circumstances, the accident was considered to have been preventable by means of eg more accessible lighting, non-slip carpeting, removal of doorsteps, more suitable arrangement of furniture and better supportive measures beside stairs. The risk of falling is found to increase markedly in persons aged 75 years or more. Prophylactic measures are recommended before patients reach this age by means of information to elderly persons and to persons involved in home care about situations involving risks. PMID- 1462384 TI - [Transfusion-associated graft-vs-host disease]. AB - Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious, often fatal complication to the transfusion of blood components. TA-GVHD is caused primarily by donor T lymphocytes reacting towards recipient MHC antigens. The diagnosis TA-GVHD should be considered when patients, within a month of receiving blood transfusion, develop sudden, unexpected high fever and erythematous rash, possibly accompanied by gastrointestinal symptoms and/or pancytopenia. Congenital (cellular) immune defect, intrauterine transfusion, bone marrow transplantation, Hodgkin's disease, and directed transfusions (especially from first degree relatives) all carry high risk of developing TA-GVHD. Since mortality exceeds 90% irrespective of any treatment, prevention is essential. Pretransfusion gamma irradiation of blood components with a 25 Gy dose effectively prevents TA-GVHD, and it is therefore recommended that all blood components be irradiated prior to transfusion to patients belonging to defined groups-at-risk. PMID- 1462385 TI - [Can the carpal tunnel syndrome be work-related?]. AB - The carpal tunnel syndrome is the most commonly reported nerve entrapment syndrome. While a number of medical risk factors are wellknown, accounting for approximately 25% af the cases, the significance of repetitive occupational hand strain has been disputed during several decades. Recently, a number of controlled epidemiological studies concerning this issue have emerged. A critical review arrives at the conclusion that jobs requiring highly repetitive and forceful sustained hand activity are associated with an increased risk for the carpal tunnel syndrome. The risk is, in particular, high when both risk factors are involved concomitantly. Exposure to hand-arm vibration also increases the risk, but it is undecided whether vibration per se or the associated ergonomic strain is the causal factor. It is argued that the evidence is sufficient to justify worker compensation and action should be taken to prevent this work-related disorder. PMID- 1462386 TI - [Kleine-Levin syndrome]. AB - The Kleine-Levin syndrome is a rare and probably underdiagnosed syndrome. It is characterized by periodic attacks of the triad: hypersomnia, vegative disturbances such as hyperphagia and hypersexuality, psychopathological changes in the level of consciousness and control of emotions. Boys and young men in the age group 10-20 years are most commonly affected. Spontaneous remission with a tendency to remission is observed and the disease "burns out" after a prolonged period of years. The etiology and pathogenesis are unknown. Theories have been propounded suggesting dysfunction of the hypothalamus. No pathognomonic findings have been observed in the early phase of sleep during the daylight hours. Central stimulating drugs have been reported to have some effect on the hypersomnia. The diagnosis is based on the clinical picture. Frequently, a long period can elapse before the diagnosis is established and some cases are never diagnosed. The literature is reviewed and is illustrated by two case reports. PMID- 1462387 TI - [Transfusion-associated graft-vs-host disease in a patient with Hodgkin's disease]. AB - Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious complication of blood transfusion which is caused by immunocompetent donor lymphocytes reacting against recipient antigens. We report a case of TA-GVHD in a male patient with Hodgkin's disease who had received several units of non irradiated blood components. TA-GVHD was diagnosed by histological examination of affected skin and demonstration of engrafted lymphocytes of female phenotype by in situ hybridization using a Y-chromosome specific probe. The need to irradiate blood components given to patients in defined risk-groups is stressed. PMID- 1462388 TI - [Juvenile renovascular hypertension of unusual origin]. AB - The case history of a girl aged 10 years with renovascular hypertension is presented. The symptoms were atypical. The diagnosis was made on basis of positive captopril renography. Angiography showed delayed filling of the right main renal artery by a long collateral vessel. The right renal artery was found to be occluded proximally by intimal hyperplasia. Renal angioplasty was performed and resulted in normalized blood pressure and normalized right kidney function. PMID- 1462389 TI - [Temporal arteritis without histological changes]. AB - A patient with severe giant cell arteritis with involvement of both eyes is presented. The symptoms were partly reversible by treatment with high doses of prednison. Three months previously (having symptoms of polymyalgia rheumatica) she had started treatment with a low dosage of prednison. Biopsies of both temporal arteries showed no signs of giant cell arteritis at that time, and the results of eye examinations were normal. The importance of follow-up on patients with symptoms of polymyalgia rheumatica, even if biopsies of the temporal arteries show no histological changes, is emphasised. PMID- 1462390 TI - [The art of finding it all. Possibilities and pitfalls of online searching]. PMID- 1462391 TI - [Are surgical masks necessary?]. PMID- 1462392 TI - [Postoperative wound infections and surgical masks]. PMID- 1462393 TI - [Should disk surgery be centralized even more?]. PMID- 1462394 TI - [Treatment of injuries in Denmark]. PMID- 1462395 TI - [Treatment of injuries in the county of Ringkobing. 1. Incidence of injuries during a period of 4 weeks]. AB - During a period of four weeks (17 September-14 October 1990) all treatments of injured persons in the five hospitals in the County of Ringkobing were registered. In addition, the refund accounts for all additional services connected with injuries submitted by the 166 general practitioners to the Danish National Health Insurance were also registered. A total incidence rate (calculated on an annual basis) of injuries requiring treatment was found to be 229/1000 og the population per annum. As compared with a similar investigation carried out in 1969, increases in incidence rates of 2.1 for admissions, 3.8 for outpatient hospital treatments and 4.4 for treatment of injuries in general practice were found. An increase in the number of minor injuries is thus concerned, probably partly conditioned by an altered threshold for seeking treatment and partly a slighter increase in the number of more serious injuries. In addition, a significant difference in the frequency of injuries requiring treatment with more numerous treatments was found in the regions of Lemvig and Ringkobing as compared with the remainder of the county. It is recommended that registration from casualty departments with collection of data for analysis of accidents be undertaken with the object of elucidating the background for the increase in the injuries and the differences between the individual regions in the county. PMID- 1462396 TI - [Treatment of injuries in the county of Ringkobing. 2. Function of the closed casualty department]. AB - The closed casualty department function in the County of Ringkobing was investigated during a period of four weeks. It was demonstrated that this functioned according to plan as the distribution general practice/casualty department was 3.4:1 and 70% of the patients in the casualty department were referred via general practice. The result of this was that the majority of minor injuries (removal of foreign bodies and treatment of wounds) were treated in general practice. In the casualty departments, there were fewer minor injuries and injuries which did not require specific treatment than are the case in open casualty departments. However, a definite diurnal variation was observed in the function of the closed casualty department as patients showed a greater tendency to seek treatment in the casualty department after working hours than during working hours and the general practitioners referred twice as many patients after working hours for continued treatment in the casualty departments. It is concluded that the closed casualty department system in the County of Ringkobing functions well but that problems may be anticipated with the function if the duty rosters for the general practitioners are altered so that the distances between general practitioners on duty increase and these have an increased work-load. PMID- 1462397 TI - [Treatment of injuries in the county of Ringkobing. 3. Attitude and behavior of the population and general practitioners in relation to treatment of injuries]. AB - This investigation describes the attitudes and behaviour of the population and the general practitioners in the County of Ringkobing concerning treatment of injuries and the closed casualty department. The investigation consists of three parts. 1. In order to describe the general practitioners in the County of Ringkobing as those who treat injuries, a questionnaire was sent to these and 88.0% replied. In general, the general practitioners had relatively great experience of work in casualty departments from their hospital appointments. Only eight (5.6%) had experience for less than six months. Practically all (93.2%) had assistance during the day but, during on-call periods, only 16.4% had assistance from doctors. Only 2.1% had access to radiographic examination in their practices. The general practitioners stated that they were able to complete treatment in 82.5% (95-50) of the patients without referral to hospital. Lack of facilities and expertise were the commonest reasons for referral to hospital. 70% considered treatment of injuries as interesting or very interesting. Only 1.4% found it boring. 2. In order to describe self referral to hospital in cases of slight injury by the population of the County of Ringkobing a questionnaire was sent to 600 of the population aged over 17 years chosen at random. 71.6% replied. 70% stated that they would contact their general practitioner or doctor-on-call in cases of wounds and suspected fracture. The individuals who would contact the casualty department, particularly in the case of wounds, were persons who lived close to the casualty department and who did not have any advantage in contacting their own general practitioner where distance was concerned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462398 TI - [Treatment of injuries in the county of Ringkobing. 4. Referral and transport of severe traffic accident traumas]. AB - In Denmark, all cases of severe injuries are referred to the nearest hospital regardless of the size of the hospital and the county boundaries. In order to investigate whether this type of referral functions according to plan, the authors investigated referral of all traffic accidents in the County of Ringkobing during the period 1 January 1983 to 31 December 1990. It was demonstrated that in only one out of 310 traffic accidents with fatal outcome, referral did not function according to plan and that the patient had been transported to a hospital which was not the nearest. It is thus concluded that referral now functions according to plan in its present form. In addition, the authors investigated whether there was any basis for establishing prehospital treatment of injuries in the country. It was found, however, that during a period of eight years (analysed on the basis of post mortem data) a maximum of 20 relevant patients would be involved annually and in whom the mortality might be reduced was concerned. Simultaneously, the average distance for transport to the nearest hospital was found to be only 12.9 km. There is thus no basis for employing massive resources for advanced prehospital service in the County of Ringkobing. With an ambulance service staffed by doctors from the anaesthetic and intensive care units of the central hospitals it is possible to provide prehospital treatment in 70% of all severe traffic injuries in the County of Ringkobing. PMID- 1462399 TI - [Genital Chlamydia trachomatis infection in abortion seekers. Strategy of examination and treatment in order to reduce the sequelae of the infection]. AB - Among women applying for termination of pregnancy, 5-17% are infected with Chlamydia trachomatis. The prevalence is higher among women under 20 years of age (12-30%), in nulliparae and when Neisseria gonorrhoeae are found simultaneously. If women applying for termination of pregnancy with Chlamydia infection are not treated, 10-60% will develop pelvic infection after abortion. Salpingitis caused by Chlamydia runs a milder clinical course than salpingitis caused by gonococci or other etiology but salpingitis due to Chlamydia is regarded as one of the most important causes of tubal infertility and extrauterine pregnancy. The symptoms may be discharge and dysuria or objective findings such as cervicitis and pathological findings in wet smears of the cervical secretion. The majority of women applying for termination of pregnancy with Chlamydia infection have no symptoms. Only few investigations have analysed Chlamydia infection in connection with sexual behaviour and association between Chlamydia infection and the number of sexual partners has been demonstrated. Direct immune fluorescent microscopic examination or enzyme immune examination of material from the cervix and urethra may be employed in women applying for termination of pregnancy on account of the rapid results. Tetracyclines and erythromycin may be employed for treatment of demonstrated Chlamydia infection. Completion of treatment prior to abortion is probably not necessary. The sexual partners should be treated. PMID- 1462400 TI - [Presence of genital Chlamydia trachomatis in abortion seekers--correlates with young age and nulliparity but not with previous genital infection]. AB - Out of 432 women applying for termination of pregnancy, 7.9% (34/428) had cervical Chlamydia trachomatis and 0.7% (3/431) genital Neisseria gonorrhoeae. The prevalence of Chlamydia was 19.2% among the women applying for termination who were under 20 years and 12.8% among those aged 21-25 years. The finding of Chlamydia among nulliparae was 14.5%. Only 2.8% of the women with Chlamydia had previously had pelvic infections. Women with Chlamydia did not have significantly greater frequency of previous venereal diseases. It is concluded that women under the age of 25 years and nulliparae who apply for termination of pregnancy should be examined for Chlamydia and should be treated in connection with the intervention. Previous pelvic infections are observed significantly more rarely in women with Chlamydia applying for termination and thus do not constitute an indication for examination for Chlamydia. It is not yet elucidated whether women with previous venereal diseases should be examined for Chlamydia. On account of the low prevalence, there are no indications for performing routine smears in women applying for termination of pregnancy for gonococci but, on the other hand it appears relevant to examine women with Chlamydia for gonococci as double infections are frequently present. PMID- 1462401 TI - [Preventive antibiotics in induced first-trimester abortion]. AB - The frequency of infection following induced first-trimester abortion is 3-5%. Duration of hospitalization is often five days, and the total costs per abortion were 5,400 Dkr (approximately pounds 500) in Denmark in 1979. Sequelae of postabortal infection are similar to and occur with the same frequency as sequelae to "spontaneous" pelvic inflammatory disease. Thus, secondary infertility was found in 10% of women with postabortal infection, spontaneous abortion in 22%, dyspareunia in 20%, and chronic pelvic pain in 14%. The risk of ectopic pregnancy is probably also increased. Surgical scrub cannot sterilize the endocervix and, as a consequence, abortion is performed in a contaminated field. The presence of pathogenic bacteria, i.e. Chlamydia trachomatis, therefore increases the risk of postoperative infection. The organism is found in approximately 7% of those applying for abortion and the risk of sustaining infection is 20%. Other risk factors are previous pelvic inflammatory disease, vaginal infection, first pregnancy and young age. Prophylactic antibiotics halve the incidence of infection, but by applying prophylaxis to risk groups only, the amount of prescriptions can be reduced. Prophylaxis need only be administered peroperatively, and tetracyclines, metronidazol, and penicillin/pivampicillin have been found to be effective. Women applying for abortion should be examined for C. trachomatis and positive cases treated no later than at the time of the abortion. PMID- 1462402 TI - [Thrombocyte aggregation and serum thromboxane B2 in patients with unstable angina pectoris treated with diltiazem or verapamil]. AB - Patients with unstable angina pectoris have increased thrombocyte aggregation and disturbances in serum prostaglandin balance. As a pilot project, we conducted a single-blind investigation of 24 patients with unstable angina pectoris treated with dilthiazem (n = 12, 240-360 mg) or verapamil (n = 12, 240-360 mg) for ten days. At the commencement of the investigation, both patient groups had hyperaggregating thrombocytes and increased serum-thromboxan-B2 (TXB2) as compared to healthy individuals (p < 0.01). In the patient group treated with dilthiazem, the aggregation threshold rose (p < 0.01), and the serum TXB2 values fell to approximately normal (p < 0.05). In the patient group treated with verapamil, no significant changes were observed in the measurements registered. The difference between the two groups remained significant during the entire therapeutic period (p < 0.01). Thus, dilthiazem appears to counteract thrombocyte aggregation in patients with unstable angina pectoris. PMID- 1462403 TI - [Unconsciousness after ingestion of nail varnish]. AB - Two males in their twenties lost consciousness after ingestion of 50 ml gamma butyrolactone. Bradycardia was observed and treated during the first hours and they recovered after a few hours. PMID- 1462404 TI - [Reversible pulmonary hypertension in a woman with connective tissue disease]. AB - The present case report describes a woman with known MCTD, who developed acute pulmonary hypertension. She was treated with methylprednisolone and had fully recovered after five days. PMID- 1462405 TI - [Control of anticoagulant treatment]. PMID- 1462406 TI - [On the Cardiologic Society, resuscitation and quality of life]. PMID- 1462407 TI - [Psychopharmacological adaptation]. PMID- 1462408 TI - [Use of psychopharmaceuticals in municipal nursing homes. A nationwide survey]. AB - In 32 nursing homes selected at random in the 16 counties in Denmark, the use of psychotropic medication was studied in all residents aged over 65 years (1454 persons) by interview of nursing staff and review of treatment records regarding drug group, dose, duration of treatment and target symptoms. Psychotropic prescriptions were recorded in 56% of the elderly. The frequency of residents receiving daily treatment with neuroleptics was 20% and for anxiolytics, hypnotics and antidepressants 13%, 33% and 11%, respectively. The duration of treatment was two to three years. The indications were mostly unspecified behavioural disturbances. The use reflects the high psychiatric morbidity in nursing home residents, especially regarding dementia. From what is known of therapeutic efficacy and side-effects, it is concluded that the prescription rate is too high, duration of treatment much longer than necessary and that drugs inappropriate for elderly are often used. PMID- 1462409 TI - [Audit--a method for quality assessment in health care]. AB - If the intentions of genuine assessment of quality and ensuring quality are to be realised in the Danish health service, it is essential that the methods employed are known and accessible. This review presents audit which is a concrete method of assessing quality. In an audit, concrete clinical cases are assessed in order to evaluate the quality of the services rendered by the health service in this instance. Assessment of quality is performed on the basis of criteria and standards for the services rendered. The conclusions end in assessment of whether the services was satisfactory or not. In connection with the unsatisfactory services, the reasons leading to this conclusion are specified. The object of an audit is to assess, ensure and raise the quality of the professional standard. By means of assessing concrete case histories the object is to identify problems of quality which could be influenced by adjustment or alteration of the practice with the object of improving the quality of the diagnosis, treatment and care. Assessment of quality in an audit should thus be carried out as a link in ensuring quality. This implies that the reasons for possible defects in quality should be elucidated. Reports should be given to the health staff involved and measures to improve quality should be worked out and instituted. After a suitable interval, the quality of the service concerned should be assessed again. International experience with audit is extensive. In a series of countries, audit is an integral part of systematic assessment of quality.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462410 TI - [The post-thrombotic syndrome. A review]. AB - The post-thrombotic syndrome which is caused by deep venous thrombosis and characterized by pain, oedema, pigmentation, eczema, lipodermatosis, varices and ulceration, is due to deficient function of the venous valves and/or obstruction of the deep veins with venous hypertension. The diagnosis may be established by investigation of the investigation of the muscular-venous pump by pletysmography or dynamic phlebography and invasive measurement of the venous pressure is not employed to any great extent. The results of valvuloplasty have, by and large, been negative. The main form of treatment is, therefore, conservative compressive bandaging which can reduce the symptoms, facilitate healing of venous ulcers and prevent recurrence of ulcers. It is emphasized, however, that this treatment must be continued consequently during the remainder of the patient's life, regardless of other treatment. PMID- 1462411 TI - [The post-thrombotic syndrome. Description and comparison of diagnostic methods: clinical examination, venous return time, phlebography and ultrasonography]. AB - Thirty-one patients with deep vein thrombosis (DVT) confirmed by phlebography 5 11 years previously were examined for the post-thrombotic syndrome (PTS). Where all of the patients were concerned, the examination included crossing-off of their symptoms of PTS on a special chart and clinical examination carried out by four doctors independently of one another, for 29 patients also determination of the venous return time by strain gauge pletysmography and for 29 patients also secondary phlebography (SF) and B-method ultrasonic scanning (UL). The degree of severity of PTS was determined by means of a scoring value which was calculated on the bases of four observers assessment of the clinical symptoms and findings. Significant differences were found for the clinical scores for legs with and without previous DVT, which shows that the method is of value despite a not inconsiderable interobserver variation. In the form employed here, pletysmography was found unsuitable for quantitating of PTS. In 60% of the patients, agreement was present between the clinical assessment, SF and UL. The necessity of agreement both as regards the diagnostic clinical criteria and as a measure for the degree of severity of PTS is emphasized. UL is recommended as a screening investigation for changes after DVT. Phlebography is only considered to be indicated in cases where detailed knowledge of the anatomical conditions is desired e.g. prior to venous surgery. PMID- 1462412 TI - [Left-side colonic ileus treated with peroperative lavage and primary anastomosis]. AB - Eight patients aged 56-85 years were operated on as emergencies because of left sided mechanical colonic obstruction. The whole colon was mobilized, a Foley catheter introduced into coecum preferably through the appendicular stump or alternatively a terminal ileotomy and a scavenger tube was introduced into the left colon proximal to the obstruction. By antegrade lavage with isotonic sodium chloride assisted manually colon was emptied, the pathological process resected and a primary anastomosis performed. No cases of anastomotic leakage or infectious complications occurred. One patient had to be operated on again because of a small wound dehiscence. The mean hospital stay was 13 days. The advantages of the treatment are that the patient is managed at the emergency operation, the frequency of complications is low and hospital stay short. It is therefore a good alternative to procedures involving temporary colostomy. PMID- 1462413 TI - [Effect of 1-year long-term treatment with sucralfate on symptomatic recurrence of duodenal ulcer]. AB - One hundred and two patients, who obtained relief from their duodenal ulcer symptoms with sucralfate (Antepsin R) in a dosage of 2 g b.i.d. for four weeks, were randomized to maintenance therapy with sucralfate 2 g at bedtime or a placebo for one year or until possible recurrence of symptoms. Ninety-four patients completed the study, 46 on sucralfate and 48 on the placebo. Eighteen of the sucralfate-treated patients (39%) experienced relapse of symptoms, as did 36 (75%) of the placebo treated patients. This difference was significant (p = 0.0008). In the sucralfate group most of the symptoms recurred within three months after randomisation, whereas the relapse rate seemed constant in the placebo group. It is concluded that 2 g sucralfate at bedtime is effective in preventing recurrence of duodenal ulcer symptoms. PMID- 1462414 TI - [Evaluation of trainee assistant education]. AB - All of the trainee assistant appointments in general practice in Denmark were assessed by means of a questionnaire investigation during a period of two years. Particular attention was paid to the quality of training and whether there were particular characteristics in the practice which provide the best training. The material consists of 360 questionnaires sent to trainee assistants in general practice one month before conclusion of the appointment. The percentage of replies was 89. The average number of years after graduation was 6.5, which is considerably higher than aimed at in future plans. The investigation reveals that the educational quality and training by the tutor did not appear to be influenced by the number of postgraduate years although there was no doubt that younger trainees required more training and supervision. The quality of training is best in one-man practices and this is followed closely by small partnerships. The investigation reveals that training by the tutor is of decisive significance. It is therefore recommended that trainees in general practice should be more closely associated with one of the practitioners responsible for training. Three fourths of the trainees found that trainee assistant appointment was better than hospital appointments in general. The investigation indicates that following should be standard in every practice: 1) own consultation room, 2) typed records, 3) an introductory leaflet and that training should be arranged with: 1) introduction, 2) half-way assessments, 3) daily conferences about individual patients and 4) weekly conferences about particular subjects related to the practice. PMID- 1462415 TI - [Overlooked posterior shoulder dislocation]. AB - Posterior dislocation of the shoulder is frequently overlooked. Early diagnosis is a prerequisite for successful treatment. Supplementary axillary or apical oblique projections should be included in the routine radiograms to confirm the diagnosis. PMID- 1462416 TI - [The hairdresser's syndrome, observatio pro]. AB - Six hairdressers with minor brain damage are presented. The etiology is discussed and the need for a study of the possible injurious factors in hairdressing-salons is stressed. PMID- 1462417 TI - [Extremely premature infants--a registry study]. PMID- 1462418 TI - [Ultrasonography of fetal abnormalities]. PMID- 1462419 TI - [Multiple trauma, rhabdomyolysis and hypercalcemia]. PMID- 1462420 TI - [Generic substitution--patients' incentives are too low]. PMID- 1462421 TI - [The synonymous preparation Andion vs. the original preparation becotide in the treatment of steroid-dependent bronchial asthma. A comparative double-blind cross over trial]. AB - Two different beclomethasone dipropionate inhalation aerosols (Andion and Becotide) were compared in a double-blind, cross-over study in patients with stable, steroid-dependent asthma. Fifty-two patients were included in the study, and 44 completed the two 6-week periods of treatment. The difference in therapeutic efficacy on FEV1 between Andion and Becotide was -0.018 1, and likewise no differences in therapeutic efficacy on FVC and peak expiratory flow were found. There were no significant differences between the two treatment periods regarding peak expiratory flow rates, symptoms, frequency of adverse effects, and amount of salbutamol and beclomethasone dipropionate employed. In conclusion, no significant differences could be demonstrated between Andion and Becotide with regard to pulmonary function, symptoms, and frequency of adverse effects in the treatment of patients with steroid-dependent bronchial asthma. PMID- 1462422 TI - [Oophorectomy per occasionem and ovarian cancer]. AB - The mortality from ovarian cancer is responsible for 450-500 cancer deaths annually in Denmark. This high mortality rate has remained unchanged for decades. No effective screening method is available. Oophorectomy per occasionem may reduce the incidence of ovarian cancer. The literature suggests a reduction in the incidence of ovarian cancer of 5.7% which corresponds to approximately 30 women annually in Denmark when OPO is performed at the age of forty or later. OPO also avoids reoperation due to the Residual Ovarian Syndrome, which is detected in approximately 2% of women after pelvic surgery. PMID- 1462423 TI - [Cardiovascular changes in arterial hypertension]. AB - In untreated essential hypertension cardiovascular structural changes will develop after some time. In arteries and arterioles, thickening and reduced compliance of the vascular wall is noted and in the left ventricle, myocardial hypertrophy. Both types of changes will enhance the risk of ischemia and of developing cardiac complications, i.e. coronary heart disease, myocardial infarction and heart failure. Methods for measurement of vascular and cardiac hypertrophy are reviewed and the value of echo-cardiographic evaluation of the hypertensive patient is stressed. PMID- 1462424 TI - [Regression of hypertensive cardiovascular changes during treatment with antihypertensive ddrugs]. AB - Antihypertensive medical treatment may induce regression of hypertensive structural cardiovascular changes after a period of time: Hypertrophy of the left ventricle and of the smooth muscle layer in the resistance vessels. In this paper, we refer to significant human studies, published during the last decade, concerning the degree of regression of these presumably secondary structural changes, resulting from antihypertensive treatment. It has been shown that most antihypertensive regimens in common use, calcium antagonists, ACE inhibitors and most beta blockers, but not diuretics and nonspecific vasodilators, are, when effective in lowering blood pressure, also capable of inducing a probably complete regression of the cardiac hypertrophy. However, complete regression of the vascular changes has not been shown. PMID- 1462425 TI - [Intrauterine hematoma in threatened abortion]. AB - In order to demonstrate the consequences of intrauterine haematoma demonstrated by ultrasound in hospitalised patients with imminent abortion, the course of pregnancy and delivery in patients with demonstrated intrauterine haematoma and patients in whom intrauterine haematoma could not be demonstrated were compared retrospectively. Intrauterine haematoma was demonstrated in 29% of patients with immiment abortion in The Department of Gynaecology and Obstetrics in Herlev Hospital. Patients with intrauterine haematoma were hospitalised more frequently and for more prolonged periods for imminent abortion and for imminent premature delivery. On the other hand, no differences were found in the frequencies of abortion, the birth weights, gestational age on delivery, number of preterm deliveries, frequencies of Caesarean section and adherent placenta between the two groups. Therapeutic bias may have been the cause of the increased number of days of hospitalisation in patients with intrauterine haematoma demonstrated by ultrasound. PMID- 1462426 TI - [Clinical usefulness of the ROMCheck Membrane Immunoassay--a new method for the demonstration of the rupture of fetal membranes]. AB - An investigation of the clinical usefulness of ROMCheck Membrane Immunoassay, a new method for the detection of amniotic fluid in the vagina, was undertaken. The ROMCheck-test is a monoclonal antibody test against fetal fibronectin in amniotic fluid. It was compared to commonly used methods as ferning, Nile blue staining of fetal cells and Nitrazine paper. We examined twenty pregnant women with suspected rupture of membranes and twenty women with apparently intact membranes receiving routine prenatal care. We found that clinical detection of amniotic fluid in the vagina resulted in a positive ROMCheck-test. When the ROMCheck-test was negative there was no indication of rupture of membranes. When the ROMCheck-test was positive and the other tests were negative, we could not exclude the possibility of the presence of amniotic fluid in the vagina at the time of examination. The test is a useful tool in identifying the presence or absence of amniotic fluid in the vagina. PMID- 1462427 TI - [HIV testing and HIV surveillance of a venereological clientele in Denmark]. AB - The object of this investigation was to evaluate the suitability of unlinked anonymous HIV screening of persons visiting one of eight out of the nine Danish clinics for venereal diseases in the national HIV surveillance. Data were collected during the period July 1, 1990-March 31, 1991 and included: gender, sexual orientation, history of intravenous drug use (IVDU), syphilis testing and HIV testing. A total of 7,455 persons participated of whom 75% were tested for HIV antibodies. The HIV test activity was significantly higher among male IVDUs than homo/bisexuals, and higher among female IVDUs than heterosexuals. The overall HIV prevalence among tested individuals was 0.6%, ranging from 0.1% among heterosexual women to 5.3% among female IVDUs. A total of 81% were tested for syphilis with an overall HIV prevalence of at least 1.1%, ranging from 0.2% among heterosexuals to 9.3% among homo/bisexual men. Since the non-participation is great and the venereological clientele is very heterogeneous, using blood taken for syphilis serology from this group for unlinked anonymous HIV screening, would not be particularly important as a supplement to the Danish HIV surveillance. PMID- 1462428 TI - [The ring chromosome 14 syndrome]. AB - Two children with ring chromosome 14 are described. Both children have only few phenotypical features suggestive of a chromosome abnormality. Both have, however, epilepsy which is typical for the ring chromosome 14 syndrome. Chromosome examination is recommended in children with mental retardation and epilepsy which is refractory to treatment. PMID- 1462429 TI - [Ring chromosome 18]. AB - Ring chromosome 18 (46,XX,r(18)) has previously been reported in about 70 patients. Another patient with the well-known physical and cytogenetic characteristics and, in addition, skeletal abnormalities in the feet, is presented here. PMID- 1462430 TI - [Psychiatry--a medical specialty. Research, education, organization]. PMID- 1462431 TI - [Prednisolone or naloxone in spinal injuries]. PMID- 1462432 TI - [The fat canard of Christmas]. PMID- 1462433 TI - [Vaccine--treatment of the future?]. PMID- 1462434 TI - [Prevention of pneumococcal infections in the elderly by vaccination]. AB - Streptococcus pneumoniae still causes serious infections especially in elderly people, despite relevant antibiotic treatment and intensive therapy. At present, Statens Serum-institut annually receives about 650 pneumococcal strains isolated from blood and cerebrospinal fluid for typing from the departments of Clinical Microbiology in Denmark. Of these strains about 55% were isolated from persons aged 60 years or older. The incidence of pneumococcal pneumonia in elderly people is said to be 4-8/1000 persons/year in countries similar to Denmark. In the USA, pneumococcal vaccination is recommended for groups at risk including immunocompetent adults > or = 65 years old. Since 1978, pneumococcal vaccine has been available in Denmark, where the only indication for vaccination has been and still is intended or already performed splenectomy in persons older than two years of age. According to the literature, the protective efficacy of vaccination of elderly persons is 60-70%. Since vaccination is, furthermore, without risks we believe that vaccination of elderly people in Denmark should be advised. PMID- 1462435 TI - [Sex chromosome abnormalities and sex determination genes. Review of the literature]. AB - Molecular analysis of structural chromosomal abnormalities, involving the sex chromosomes, has provided us new knowledge concerning sex determination in humans. This has raised three hypotheses of sexual differentiation, which will be discussed even though none of these can explain all abnormalities involved. Meiotic recombination which normally takes place during the male meiotic cell division, can give rise to sex reversal syndromes such as XX male and XY female, if crossing over is abnormal. Analysis of these abnormalities has made it possible to map sex determining regions on chromosome Y, and to construct a deletion map. Methods using DNA probes, are capable of identifying Y-specific sequences in persons with sex reversal. This means a more optimal counselling, possibilities of prenatal diagnosis, and opportunities for selecting patients with risk of gonad cancers, for extirpation. PMID- 1462436 TI - [Ultraviolet rays and skin cancer]. PMID- 1462438 TI - [Measurement of intestinal blood supply in patients with suspected intestinal ischemia]. AB - The object of the investigation was to illustrate the diagnostic yields of measurement of the intestinal blood supply before and after a test meal and of abdominal angiography recorded in patients in whom chronic intestinal ischaemia is suspected. A retrospective review including 18 patients (age range 36-79 years) was undertaken. The diagnosis of chronic intestinal ischaemia was established in four patients on the basis of measurement of the blood supply to the intestine and abdominal angiography and vascular reconstructive interventions could be performed. These interventions were technically successful in three cases. Control flow measurement was only performed in one patient after the operation. This showed normalized postprandial blood flow. By large, measurements of the blood supply to the intestine were free from complications. In cases of suspected chronic intestinal ischaemia, the combination of abdominal angiography and measurement of the blood supply to the intestine appear to supply the necessary information for selection of patients for vascular surgical interventions. PMID- 1462437 TI - [Identification of Y chromosome material in an XX male by means of fluorescent in situ hybridization]. AB - This article describes a case of 46,XX male, the most frequent form of sex reversal syndromes in humans. A method of identifying Y chromosome material in these and other patients with structural chromosomal abnormalities involving chromosome Y is given. Chromosomes from a phenotypically normal male child without any congenital malformation, where prenatal diagnosis revealed the female karyotype 46,XX, were analysed using fluorescence in situ hybridisation (FISH). The analysis revealed an X chromosome, containing Y chromosome sequences on the tip of the short arm. The sequences are not normally visible in conventional cytogenetic analyses of XX males. The breakpoint on Y was determined to be in the region of Yp11.2, which is proximal for the putative sex determining gene on Y. The results are consistent with theories of abnormal crossing-over during the paternal meiotic cell division where meiotic recombination can give rise to structural abnormalities, which can then cause sex reversal syndromes. Prenatal diagnosis of structural sex chromosome abnormalities has become available using the FISH method. PMID- 1462439 TI - [Urethral stricture in Greenland]. AB - In a retrospective survey, the 46 patients treated for urethral stricture at Dronning Ingrids Hospital, Nuuk, (the main hospital in Greenland) during the four year period August 1987-August 1991 are investigated, and the consequences of not treating urethral stricture are illustrated by a case. The patients are middleaged and older men generally with long and multiple strictures close to the sphincter. Gonorrhoea is the common cause of the stricture. The patients have obstructive symptoms, urinary infections and haematuria. Furthermore, nearly 1/4 of the patients have complications in the form of scrotal and perineal abscesses, and reduced renalfunction and rapidly lethal disease because of sepsis are seen. The urethral strictures tend to recur after treatment. Urethral stricture disease is undoubtedly underestimated in Greenland, and the investigation stresses this serious complication of venereal disease. PMID- 1462440 TI - [Epidemiological studies on scalded children admitted to the burns unit at the Hvidovre hospital during 1981-1990]. AB - During the ten year period 1981 to 1990, a total of 436 children aged 0-5 years were admitted for scalds at the Burns Unit of Hvidovre Hospital. We did not find any reduction in the number of admissions during this period nor was any change in the patterns of scalds found. Water, tea and coffee were the main causal agents of scalds and the dominant group of scalded children was between the ages one to two years. In 37% of cases, the scalds required grafting and the average stay in hospital was 16 days. The background for this unchanged pattern could be that the prophylactive campaigns have been insufficient. PMID- 1462441 TI - [Combination therapy with pamidronate and calcitonin in hypercalcemic crisis caused by primary hyperparathyroidism]. AB - Pamidronate (aminopropylidene diphosphonate, APD) is known to be an effective agent in lowering plasma calcium in cancer associated hypercalcaemia and in primary hyperparathyroidism. Combined therapy with pamidronate and calcitonin has proved efficient in the treatment of severe cancer-associated hypercalcaemia. A 66-year-old woman in hypercalcaemic crisis caused by primary hypreparathyroidism was successfully treated with this combined therapy. Albumin corrected plasma calcium was 5.26 mmol/l on arrival and the PTH level was very high. The combined therapy lowered the plasma calcium to normal and made it possible to perform elective parathyreoidectomy. A 5.8 g parathyroid adenoma was removed. It is recommended to consider combined therapy with pamidronate and calcitonin in the emergency management of hypercalcaemic crisis. PMID- 1462442 TI - [Quality assurance or research]. PMID- 1462443 TI - [Erythropoietin in treatment of pruritus in chronic renal failure]. PMID- 1462444 TI - [Malignant melanoma of the skin in Denmark]. PMID- 1462445 TI - [Information about sterilization]. PMID- 1462446 TI - [Optimal treatment of women with breast cancer]. PMID- 1462447 TI - [Axillary dissection in primary surgical treatment of breast cancer: risk of false-negative axillary status]. AB - The present study evaluates the extent of axillary dissection as part of the primary surgical treatment of operable breast cancer. Data are from the period January 1979 to August 1990 and were collected prospectively as part of the Danish Breast Cancer Cooperative Group protocols for low-risk mammary carcinoma. The series consists of 6774 breast cancer patients aged 69 years or younger. The number of axillary lymph nodes removed was related to the frequency of ipsilateral axillary recurrence, recurrence-free survival, and overall survival after a median of five years follow-up, respectively. The recurrence-free survival and overall survival rate were directly related to the number of axillary lymph nodes removed. The difference in outcome is believed to be caused by false-negative classification of axillary-positive high-risk patients in groups of patients where only a few axillary lymph nodes were removed. PMID- 1462448 TI - [Determination of estrogen receptor status in breast cancer by immunocytochemical examination of fine-needle aspirates]. AB - Estrogen receptor status was determined by immunocytochemical examination of fine needle aspirates in 109 cases of primary invasive breast carcinoma. The results were compared with those from biochemical determination performed on tumor cytosols. Positive agreement was found between qualitative determination (positive/negative) by the two methods in 83% of the cases, and after semiquantitative stratification into three groups the results corresponded in 76%. The predictive value of a positive result on fine-needle aspirate was 96%, and 57% of a negative result. It is concluded that immunocytochemical determination of estrogen receptor status of breast carcinomas on fine-needle aspirate with the applied technique cannot replace the current standard biochemical method. PMID- 1462449 TI - [What do we know about consultation hypertension?]. AB - This review article examines the essential literature concerning "white coat" hypertension. It is stated that "white coat" hypertension is present in approximately 20% of patients with diagnosed mild to moderate hypertension. It is concluded that the pathophysiology of "white coat" hypertension is incompletely investigated; that the prognosis for untreated "white coat" hypertension seems fair; medical treatment being scarcely required. It is concluded further that more accurate diagnosis of mild to moderate hypertension, including the use of ambulatory blood pressure monitoring, will reduce the overall expenses by approximately million Danish crowns annually (approximately 2,000,000 pounds). PMID- 1462450 TI - [Consultation hypertension diagnosed by 24-hour ambulatory blood pressure monitoring. A study of 159 patients with recently diagnosed hypertension]. PMID- 1462451 TI - [Treatment of hemangioma in children with recombinant interferon]. AB - Pulmonary haemangiomatosis and large haemangiomas endangering vital structures and with a potential association of consumptive coagulopathy are rare but severe diseases in infancy and childhood. Therapy with glucocorticoids, cytostatics and surgical intervention has not proved satisfactory. From experience with Kaposi's sarcoma, about 20 children with severe forms of haemangiomatous disease have now been treated with alpha-interferon with promising results. Mechanisms of action are unknown, but these could include a cytostatic effect, inhibition of the abnormal proliferation of endothelial cells, fibroblasts and smooth muscle cells. Furthermore, alpha-interferon could inhibit the paracrine and autocrine effects of locally produced growth factors. Also, alpha-interferon could promote the production of prostacyclin, which inhibits platelet aggregation, leading to reduced damage and consumption of platelets. Long term treatment is mandatory. Initial daily doses of 2 to 5 million U/m2 are administered subcutaneously. Side effects in this dosage interval are uncommon in childhood. Future studies are needed to establish exact guidelines for the use of alpha-interferon in childhood, but the clinical experience hitherto obtained points to the fact that treatment is effective in severe forms of haemangiomas and pulmonary haemangiomatosis. PMID- 1462452 TI - [Salicylic acid poisoning]. AB - The study analyses the role of salicylic acid (SA) in fatal intoxications with special reference to potentially avoidable, accidental poisonings. The study indicates a relation between SA intoxication and the presence of an infection of the respiratory tract. All deaths in Denmark in the period 1980 through 1989 registered as caused by SA were analysed as were all deaths submitted to forensic toxicological examination in a defined region of Denmark in the years 1985 through 1989. During the decade 1980 through 1989 the number of fatal intoxications due to SA increased from approx. five per year to approx. 23 per year. During the same period the sales of SA decreased. Many deaths in the material were registered as accidental, and an increasing frequency of accidental deaths was seen with a lower social level. Frequently, an infection of the respiratory tract was either indicated in a hospital case record or a police report, or found at autopsy. PMID- 1462453 TI - [Value of routine follow-up after infrainguinal arterial reconstruction]. AB - Longterm patency of infrainguinal bypass procedures may be established on the basis of clinical evaluation and ankle pressure measurements. With the aim of assessing whether these parameters could predict grafts at risk for occlusion, we identified 24 patients in whom the bypass had occluded between 3 and 12 months postoperatively, but following at least one follow-up. These patients were compared with a control group consisting of further 24 patients operated on during the same period, but in whom the bypass was patent. Prior to graft occlusion only nine (39%) patients had complained of claudication, and a significant drop in ankle pressure was demonstrated in seven (29%) patients. These figures were significantly higher than the one (4%) patient in the control group who complained of claudication and the other (4%) patient who developed a drop in ankle pressure (p < 0.02 and 0.05, respectively). Graft surveillance based on patients' history and ankle pressure measurements are insufficient parameters for identification of grafts at risk for occlusion. However, the occurrence of claudication and/or a significant drop in ankle pressures are associated with a high incidence of graft thrombosis. PMID- 1462454 TI - [Asymptomatic benign mediastinal teratoma]. AB - A case of asymptomatic benign mediastinal teratoma is presented. The necessity for definite diagnosis of mediastinal tumours is stressed together with the need for conferences involving several specialties. PMID- 1462455 TI - [Colchicine treatment of recurrent steroid-dependent pericarditis in a patient with post-myocardial-infarction syndrome (Dressler's syndrome)]. AB - The usual treatment of pericarditis consists of non-steroid anti-inflammatory agents. In cases where the symptoms and/or the pericardial effusion persist or progress, the disease can be arrested in the majority of cases by employing steroids. In some patients, it may prove difficult to conclude steroid treatment as gradual withdrawal results in recurrence and it may, therefore, be necessary to continue with large doses of steroid for prolonged periods. There is, however, a possibility for another form of treatment. The present authors present the case history of a patient with pericarditis on the basis of the post-myocardial infarction syndrome and in whom the symptoms recurred several times during attempts at gradual withdrawal of prednisolone. Treatment with colchicine was commenced. The patient rapidly became symptom free and has now been symptom free for 45 weeks without prednisolone. Colchicine was withdrawn after 33 weeks without recurrence. It is considered that trial of colchicine treatment can be recommended in cases of recurring pericarditis particularly when there are problems (recurrence) on attempted withdrawal of steroid treatment. Naturally, it is important to exclude specific causes requiring other forms of treatment as the cause of the pericarditis (e.g. malignant disease, tuberculosis, systemic disease etc.). PMID- 1462456 TI - [Passive smoking and lung cancer--among dogs]. PMID- 1462457 TI - [Problematic Danish AIDS policy]. PMID- 1462458 TI - [Silicone breast implants and connective tissue diseases]. PMID- 1462459 TI - [On ketamine]. PMID- 1462460 TI - [Disinformation and scientific honesty in nutritional research]. PMID- 1462461 TI - [Did did the risk of recurrent tubal pregnancy increase because of conservative treatment?]. PMID- 1462462 TI - [Iron supplementation to pregnant women is again "in"]. PMID- 1462463 TI - [Sudden, unexplained infant death--sudden infant death syndrome. Forensic pathological aspects]. AB - Delimitation of the sudden unexplained infant death syndrome (SIDS) is difficult as the diagnosis is made by exclusion. The difficulties in the differential diagnosis are concentrated on interpretation of the significance of positive viral and bacterial findings, inflammatory changes in the respiratory organs, heart and central nervous system together with malformations. Classification of SIDS appears, therefore, to vary according to time and place. New techniques, e.g. DNA analysis, have explained the etiology in a few per cent of the cases but have not yet solved the riddle of SIDS. The article reviews hypotheses about apnoea, arrhythmia, overheating and inefficient surveillance of the infant. It is emphasized that assessment of risk factors for SIDS requires valid epidemiological investigations where the basis for the diagnosis is a uniform classification of SIDS infants as compared with other groups of sudden death in infancy. An investigation of this nature has been initiated in the Nordic countries. It is important to examine and treat infants with abnormal sleep apnoea but generalized employment of monitoring has not reduced the number of unexplained infantile deaths. PMID- 1462464 TI - [Significance of sleeping position on the occurrence of sudden, unexplained infant death. An epidemiological review]. AB - The cause of the sudden infant death syndrome (SIDS) is, according to the definition, unknown. Epidemiological research during recent years has identified a series of probable risk factors. One of these is the use of prone position as sleeping position. In the Western European countries, Australia and New Zealand, a total of 14 case-control studies illustrate a possible connection between the prone position and SIDS. Eleven of the studies revealed a significantly increased relative risk (RR) of between 1.4 and 12.5 for SIDS when using the prone position, while the three remaining studies did not demonstrate increased RR. A meta-analysis of the results of the 14 case-control studies showed an RR of 2.4 for SIDS in the prone position as compared with other sleeping positions. In a single prospective cohort study from Australia, an RR of 3.1 was found for SIDS in the prone position. Interventions in which parents are advised not to place the infants in the prone position during sleep appear to have resulted in considerable reduction in the number of cases of SIDS according to preliminary reports from Great Britain, the Netherlands, Norway and New Zealand. A series of methodological problems can be demonstrated in the published results of these studies, including limited size of study populations, inadequate matching of control groups and absent confounder control. Nevertheless, the total epidemiological evidence, also where Denmark is concerned, speaks in favour of altered recommendations for sleeping positions of infants, particularly because there is no documentation to suggest that the prone position offers any advantages to health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462465 TI - [Favourite sleeping positions among infants in the county of Roskilde. Is there a connection with sudden, unexplained infant death?]. AB - The purpose of this study was to investigate the distribution of the favourite sleeping positions and other possible risk factors for SIDS among infants in a Danish county, and to compare the distribution af sleeping positions with the sleeping positions reported in SIDS-cases from the same district. Information about favourite sleeping positions at the age of one month and four months was collected by interviews with parents, performed consecutively by health visitors at the routine examinations of 174 infants aged eight months. Information about sex, birthweight, gestational age, complications of delivery, mother's age and maternal smoking in pregnancy was collected for each child from the Birth Registration form. Thirty-two SIDS-cases from the 10 year period 1982-91, mostly based on police reports, were analysed retrospectively as regards sleeping positions and other possible risk factors. The distribution of different sleeping positions at the age of one month/four months was: prone 59%/52%, lateral 39%/41%, supine 2%/6%. There was a significant negative correlation between birthweight and use of the prone position. Among the SIDS-cases, the prone sleeping position was reported in 18 of 21 cases (86%), where this information was available. In conclusion, the prone sleeping position seemed to be associated with an increased risk of SIDS (estimated OR 4.1) but some of this difference can be accounted for by the more frequent use of this position among children with low birthweight and other risk factors. PMID- 1462466 TI - [Testing an ultrasonic scanner for determination of urinary bladder volume]. AB - Bladderscan BVI 2000 is a portable ultrasound scanner, specially constructed for determination of bladder volume. We have tested this scanner for accuracy, systematic errors and the training required to use it. The bladder volumes measured by ultrasound scanning were compared with the true volumes. Fifty-six measurements were made. We found the accuracy of BVI 2000 sufficient to determine bladder volumes as either small or large. We found no systematic errors. No special training is required to use the scanner. The device is thus useful in most clinical situations when greater accuracy than indicated here is not necessary. PMID- 1462467 TI - [Cystectomy for urinary bladder cancer. Postoperative complications and mortality]. AB - During a period of ten years, 111 patients with cancer of the bladder were treated by total cystectomy. In 69 patients a preoperative radiation dose of 40 Gy was administered, 23 received 60 Gy and 19 received no radiation. The crude survival was 50%. The postoperative mortality was low, 3.6%. PMID- 1462468 TI - [Primary malignant pleural neoplasms. Diagnostic code 163.09]. AB - The code 163.09 indicates a primary malignant pleural neoplasma-malignant mesothelioma. We have reinvestigated 173 patients, who were discharged from a department of pulmonary medicine with this code number during a 8 1/2 year period. A revision during which repeated biopsies, course of the disease and, in some cases, autopsy were considered, revealed that 63 were confirmed as having a malignant mesothelioma, 94 had neoplastic disease secondary to malignancy elsewhere, 13 had benign changes and in three cases the records were missing. Malignant mesothelioma entitles the patient to compensation if he has worked with asbestos. An occupational history was present in 94% of those suffering from mesothelioma and in 71% of the remaining patients. Among patients with mesothelioma a history of asbestos exposure was obtained in 44%, a history of no exposure in 22% and no specific mention of asbestos in 34%. In the group of patients who did not have mesothelioma 14% had known exposure to asbestos, eight none and in 78% no specific information concerning asbestos was available. Twenty three of the 63 patients with mesothelioma had been notified to the workmens' compensation board. Retrospectively, we found that 12 more patients should have been notified. Eight patients who did not fulfil the criteria for malignant mesothelioma had erroneously been notified to the board for compensation. We find that code 163.09 frequently has been used as a working diagnosis, which could not invariably be substantiated. Although malignant mesothelioma had been suspected, previous history concerning asbestos exposure was often incomplete or absent. A correct occupational history and aggressive bioptical procedures are essential in all cases where malignant mesothelioma is suspected.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462469 TI - [Pseudomonas infection associated with whirlpool bath]. AB - After using a whirlpool-spa when the chlorine concentration in the water was very low (0.1 mg/l free chlorine) approximately 20 persons developed a follicular rash. No cases were registered in bathers when the chlorine concentration was acceptable (0.9-1.2 mg/l). The same sero-group and phagetype of Pseudomonas aeruginosa was cultivated from a patient and from the piping system of the spa. The importance of following directions for the installation of whirlpool-spas and regulations for their operation and control is strictly stressed. The National Agency for Environmental Protection is asked to reinforce the existing regulations concerning whirlpool-spas. PMID- 1462470 TI - [Pseudomonas bacteremia developing after whirlpool bath]. AB - Whirlpools may be responsible for transmission of microbial infections among the bathers if the technical hygienic conditions in the care of the bath are not observed. Two cases of infection with Pneudomonas bacteria were observed after use of whirlpools in a deluxe summer chalet. On the basis of the documented cases, the necessity for specific requirements concerning the installation, running and control of whirlpools used commercially should be considered. In their advisory brochures, the responsible authorities should ensure that the requirements made concerning whirlpools should be intensified so that these baths in summer chalets which are rented out should be subject to public control. Owners and users of whirlpools should be aware of the importance of meticulous hygiene in their care. PMID- 1462471 TI - [Acute myelo-meningo-radiculitis caused by the spirochaete Borrelia burgdorferi]. AB - A case of severe myelo-meningo-radiculitis with Lyme neuro-borreliosis is described in a patient aged 33 years suffering from insulin dependent diabetes mellitus. It is essential to examine the cerebro-spinal fluid for Borelia burgdorferi specific intrathecal antibody production if sensory radiculitis persist and, finally, if there are focal motor signs and unexplained lymphocytic pleocytosis in the cerebro-spinal fluid. Early diagnosis is very important in order to shorten the course of the illness and recovery. PMID- 1462472 TI - [Anxiety symptoms and depression]. PMID- 1462473 TI - [Anaphylactic shock]. PMID- 1462474 TI - [While the grass grows the steed starves]. PMID- 1462475 TI - Changes in action potential kinetics following experimental bladder outflow obstruction in the guinea pig. AB - The effect of experimental bladder outflow obstruction on membrane electrical activity of guinea pig detrusor smooth muscle was studied. Using an intracellular microelectrode technique, action potentials were recorded from single smooth muscle cells to determine the effect of outflow obstruction on action potential (AP) kinetics. Bladder outflow obstruction resulted in smooth muscle hypertrophy with bladder weight gain to 2.7 times control levels after 8-12 weeks' obstruction. The changes in the AP kinetics noted with obstruction-induced bladder hypertrophy were a prolongation of the AP duration and a decrease in the maximum velocity of depolarization and repolarization. The AP amplitude, after hyperpolarization and overshoot potential in addition to the resting membrane potential (RMP) did not change significantly with bladder outflow obstruction. The values of these AP parameters were not affected significantly by the application of atropine and guanethidine in smooth muscle tissue from either control or obstructed bladders. These results suggest that the active electrical properties of the detrusor smooth muscle membrane are changed significantly by obstruction-induced bladder hypertrophy. Furthermore, the results suggest that adrenergic and cholinergic neurotransmitters do not contribute to these changes in AP kinetics following obstruction. The changes in AP properties with outflow obstruction-induced bladder hypertrophy were compared with those previously reported for the hypertrophic myocardium and were discussed in relation to the known impaired contractile properties of obstructed bladder smooth muscle. PMID- 1462476 TI - Effects of bacteria involved with the pathogenesis of infection-induced urolithiasis on the urokinase and sialidase (neuraminidase) activity. AB - It has been hypothesized that urinary urokinase and sialidase may play a role in urolithiasis. If these theories have substance it is to be expected that microorganisms may also affect these enzymes, since the association between urinary tract infection and renal stone formation is well known. It is generally assumed that Proteus mirabilis and Staphylococcus albus, which produce the urea splitting enzyme urease, are responsible for stone formation. However, the importance of non-urease-producing microorganisms (Escherichia coli and Enterococcus) in urolithiasis is unclear. Spectrophotometric studies were therefore devised to clarify this problem. Microorganisms associated with infection-induced stones (Proteus mirabilis and Escherichia coli) respectively inhibited the urokinase and stimulated the sialidase activity. In contrast, microorganisms which were not associated with infection stones (Bacillus subtilis) had significantly less effect on urokinase and sialidase activity. This study may explain infection-induced stone formation and could open a completely new line of research. PMID- 1462477 TI - In vitro adherence of Staphylococcus saprophyticus, Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus aureus to human ureter. AB - Staphylococcus saprophyticus adhered to human ureteral epithelium in vitro. The levels of adherence, which were determined quantitatively with the scanning electron microscope, correlated well with bacterial hemagglutinating activities with sheep erythrocytes (r = 0.9459, P < 0.01). Transmission electron microscopy revealed that the adhering bacteria and the hemagglutinating bacteria possessed similar pili-like structures on their cell surfaces. Staphylococcus epidermidis, Staphylococcus haemolyticus, and Staphylococcus aureus did not adhere to the epithelium. Only S. aureus adhered markedly to the connective tissue of the ureter, and adhesion of this organism was direct via its cell wall. This adherence test system clearly showed up differences in the abilities of these staphylococcal species to adhere to the urinary tract. PMID- 1462478 TI - The effect of repeated instillations of antiseptics on catheter-associated urinary tract infections: a study in a physical model of the catheterized bladder. AB - The activity of three antiseptic bladder washout solutions was examined in a physical model of the catheterized bladder. Tests were performed against cultures of four common urinary tract pathogens that had established themselves in the model and colonized the surfaces with biofilm. Double instillations of chlorhexidine (0.02% w/v) at 6-h intervals failed to eliminate Pseudomonas aeruginosa, Proteus mirabilis, and Providencia stuartii from the bladder model. Escherichia coli, however, was susceptible to a second instillation provided that it was performed within 12 h. Supplementing chlorhexidine with EDTA and TRIS potentiated its activity against E. coli. Mandelic acid (1.0% w/v) was the most effective of the agents, double instillations eliminating all but Pr. mirabilis infections. PMID- 1462480 TI - Study of kidney and liver viability in the rat after exclusive aortic perfusion using intracellular ATP measurement. AB - To find whether the liver can be procured after exclusive aortic perfusion, three organ perfusion models were used in three groups of donor rats. Group 1 underwent liver wash-out via the portal vein; in group 2, the kidneys alone were perfused via the aorta; and group 3 underwent simultaneous aortic perfusion of liver and kidneys. All perfusion flow rates in the three groups were adjusted to physiological values. Harvested organs were transplanted and recipient animals were killed 4 h after transplantation to study liver and kidney viability by using intracellular ATP measurement. Liver ATP was lower (P < 0.005) in the portal perfusion group (group 1: 1.396 +/- 0.412) than in the aortic perfusion group (group 3: 2.181 +/- 0.061). Kidney ATP was comparable in groups 2 and 3:1.066 +/- 0.09 vs 1.059 +/- 0.273 (mumol/g) tissue). Liver cooling was quicker with portal perfusion than with the aortic flush (20 degrees C in 20 s vs 15 degrees C in 60 s). Aortic perfusion at a physiologic flow rate has no detrimental effect on renal viability studied by intracellular ATP measurement. We conclude that liver cooling via the aortic route only is a good alternative to portal perfusion and seems to give good preservation. Application of this observation to emergency procurement in humans is still the subject of controversy. PMID- 1462479 TI - Urinary trypsin levels observed in pancreas transplant patients with duodenocystostomies promote in vitro fibrinolysis and in vivo bacterial adherence to urothelial surfaces. AB - This study evaluated the role of activated urinary trypsin in mediating the increased incidence of infectious and hemorrhagic lower urinary tract complications in pancreas transplant patients with pancreatico duodenocystostomies (PDC). The effect of trypsin concentrations corresponding to those observed in the urine of PDC patients were studied using an in vitro assay of clot lysis and an in vivo assay of bacterial-urinary tract adherence. Results were compared with those of parallel assays performed using urine from a pancreas transplant patient with a duodenocystostomy and control human urine. All trypsin concentrations studied demonstrated fibrinolytic activity. Fibrinolysis increased as a direct function of both trypsin concentration and duration of substrate exposure (P < 0.0001). Fibrin lysis resulting from the urine of the transplant patient was 4.6 times greater than that predicted based upon assays of total trypsin content in the sample. Fibrinolytic activity in control urine specimens was 0.16% of that observed in transplant urine specimens. Exposure of the rat urinary bladder to 200 micrograms/ml trypsin concentrations, or transplant urine, resulted in a significant increase in bacterial adherence over that seen in control urine from treated animals (P < 0.05). These findings demonstrate a significant effect of urinary trypsin on physiologic processes involved in hemostasis and the prevention of urinary tract infection. Active urinary trypsin may play an etiologic role in hemorrhagic and infectious lower urinary tract complications observed in patients with a PDC. PMID- 1462481 TI - Renal effect of dopexamine hydrochloride in patients with chronic renal dysfunction. AB - Dopexamine hydrochloride, a dopamine analogue, has been reported, both experimentally and clinically, to increase renal blood flow (RBF) and improve renal function in normal kidneys. The availability of computer-enhanced radionuclide scintigraphy, which provides accurate non-invasive measurement of changes in RBF, enabled us to study the renographic effects of dopexamine hydrochloride in patients with chronic renal dysfunction (CRD). Ten patients suffering from CRD and ten normal kidney donors were the study population. Renography was performed, heart rate (HR) and blood pressure (BP) measured, and hematological and biochemical tests carried out before and after intravenous infusion of dopexamine 2 micrograms kg-1 min-1 for 60 min. The patient population displayed significant increases in total cortical and medullary RBF and renographic clearance rate (CR), while in kidney donors the RBF was increased in all kidney regions with no change in CR. HR increased in both groups, while BP showed no significant changes. The hematological and biochemical changes were transient and returned to preinfusion levels after 24 h. It is concluded that dopexamine hydrochloride 2 micrograms kg-1 min-1 increases RBF and CR in patients with CRD. PMID- 1462482 TI - Low-voltage coagulation for welding sutures watertight: an experimental study. AB - A rat model was developed to test the watertightness of sutures. In this model it was proved that welding by use of low-voltage coagulation current did not improve on the watertightness obtained with conventional skin suturing. The mean leak pressure after welding was about 4.2 cm H2O, i.e. statistically significantly lower than the mean leak pressure of the conventional suture, which is 14.1 cm H2O. Neither addition of protein solder nor an additional conventional suture improved these results. It is therefore concluded that low-voltage coagulation is unsuitable for welding tissues. PMID- 1462483 TI - [Sex differentiation disorders from the andrologic viewpoint]. AB - Abnormal sex differentiation with ambiguous genitalia now leads to prompt and comprehensive diagnostic evaluation in the neonate. If necessary, phenotypic gender assignment is done very early and appropriate surgical correction is performed. Management at puberty and later is more difficult. Andrological guidance at this time covers problems of genital identification, sexuality and fertility. The different types of abnormal differentiation, i.e. genetic, gonadal and phenotypic alterations, may result in different andrological problems, e.g. hypogonadism including micropenis and undescended testes, lack of secondary sex characteristics and impotence. With respect to fertility the major problems are testicular azoospermia and/or congenital abnormalities of the male reproductive tract. Any proposals for treatment have to take account of all these different aspects of pathogenesis and the natural course of the disease. In each case, andrological guidance must be formulated with due consideration for the results of genital determination in childhood, including surgical correction. PMID- 1462484 TI - [Treatment of hypospadias]. AB - Treatment of all forms of hypospadias is difficult. Several abnormal components have to be differentiated and corrected in a very tight space, in addition to which the blood supply must be preserved and infection prevented. Technical progress now allows early correction (around the age of 12 months) in a single procedure, using methods that date back to the last century. Cosmetic results are as important as functional ones. The glans should be reconstructed around the neomeatus, and the penile shaft should be straight. Microsurgical techniques, short transurethral urinary diversion and reliable dressings are important. Strategies, the sequences of surgical procedures and a selection of practical methods are presented and discussed. PMID- 1462485 TI - [Treatment of bladder exstrophy. Reconstruction or urinary diversion]. AB - Bladder exstrophy is seen in 1 of 30,000-40,000 live births, and is seldom treated in many urological departments. Treatment options for children with exstrophy are upper urinary tract diversion or reconstruction of the bladder and plastic surgery of the bladder neck to gain urinary continence by the age of 4-7 years. Historical reviews report continence rates of 10-30% after a staged approach with primary reconstruction and secondary bladder neck repair. This formerly meant upper urinary tract diversion as a third stage in 70-90%. Multiple operative procedures could be avoided when primary diversion was done. The best results were reported following antirefluxive implantation of ureters into the sigmoid colon (ureterosigmoidostomy). In boys, the base of the bladder was removed, leaving a small residual bladder which together with the reconstructed epispadias served as a "seminal tract". Total removal of the bladder was performed in girls. Long-term follow up of upper urinary tract diversion showed disturbances of serum electrolytes, urinary tract infections and stone formation, and after ureterosigmoidostomies an increased rate of colon carcinomas was documented. These results led to renewed interest in reconstruction. The technique of bladder neck reconstruction was changed, resulting in a higher rate of late urinary continence: augmentation cystoplasties, clean intermittent catheterization and the artificial sphincter help to achieve a continence rate of more than 90%. This goal was reached only after multiple operations and without knowledge of the long-term sequelae of augmentation cystoplasties. The years to come will show whether new concepts of ureterosigmoidotomies, such as the sigma rectum pouch, will be preferable, or a late urinary tract diversion after failed reconstruction. Most centers are now agreed that primary reconstruction of bladder exstrophy should be attempted in the newborn child. PMID- 1462486 TI - [Neurogenic disorders of bladder emptying in closed spinal dysraphism]. AB - Closed (occult) spinal dysraphism, e.g. lipomyelomeningocele, intraspinal lipoma, diastematomyelia, the tethered spinal cord in its various forms and dysgenesis of the sacrum, is often diagnosed late and only symptoms of neurogenic bladder dysfunction are present. A lipomyelomeningocele mostly causes detrusor and sphincter dysfunction, as was the case in five of six children among our patients. However, improvement of neurological and urological symptoms after the operation can only be achieved in about 40%. Four of eight children with diastematomyelia suffered from neurogenic bladder dysfunction; three have meanwhile undergone surgery with complete recovery in one, no relevant change in the second, and worsening in the third. Originally a specific term, the "tethered spinal cord" when associated with spinal dysraphism has taken on a more general meaning. Nowadays this term is not only used for a short, thickened and tight filum terminale, but comprises any pathology, which prevents the spinal cord from ascending. MRI examination of the craniovertebral junction and spinal cord of patients with treated myelomeningocele often reveals secondary pathologic changes: these may be areas of cord atrophy, hydromyelic cavitation or ventral compression from arachnoid cysts with clinical symptoms mostly after the age of 5 years. In these children a changing urodynamic pattern may therefore be caused by such a pathology and is an indication for a thorough neurological examination including MRI. Of all the dysrhaphic states mentioned above, sacral dysgenesis is the most frequent. The sacral osteological anomaly, as a numerical and as a structural anomaly, also determines the neuro-urological deficit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462487 TI - [Idiopathic left-sided varicocele. An ontogenetic abnormality?]. AB - Phlebograms for sclerotherapy of varicoceles were performed in 659 patients. In 484 cases no valves of the left spermatic vein could be demonstrated. However, 172 patients showed sufficient valves or absent insertions of the spermatic veins at typical point with retrograde flow through collaterals (persistent intercardinal anastomoses). The value of nutcracker phenomena I and II is discussed. Ontogenetic disorders in the development of the secondary abdominal venous system are responsible for the occurrence of the idiopathic left-sided varicocele. PMID- 1462488 TI - [Obstructive uropathy after kidney transplantation. Experiences with endourologic incision of ureteral stenoses]. AB - Between 1985 und March 1991 we have managed 8 upper urinary tract obstructions in kidney transplants using an endourological approach. After a graft rejection was excluded an obstruction was initially diagnosed by nephrosonography and further confirmed by IVP or antegrade pyelography. To investigate the urodynamic relevance of the stenosis, all patients underwent preoperative diuretic isotope renography. In all cases a percutaneous pyelostomy was done to preserve renal function. 7 of these 8 patients demonstrated a stenosis of the ureter, while in one case, the obstruction was caused by a coagulum in the renal pelvis. Incision of the stricture then was performed with a flexible knife antegrade or retrograde and stented for 4-6 weeks. In 6 out of 7 cases with a proven stenosis of the ureter, the cold knife incision lead to a successful outcome, while in one patient, the kidney had to be removed due to uncontrolled bleeding 12 days after successful percutaneous incision. Our results indicate, that the cold-knife technique for the management of upper urinary tract obstructions in kidney transplants is a promising, fast and in most of the cases effective method. Due to its minimalinvasive character and excellent results, this approach is able to replace open reintervention in most cases. PMID- 1462489 TI - [Vaginal estriol administration in treatment of postmenopausal urinary incontinence]. AB - In an open, prospective, multicenter, controlled study, 629 female subjects suffering from stress and urgency urinary incontinence were treated with vaginally administered estriol at a dose of 0.01 g daily for 3 weeks, and 0.01 g bi-weekly for a further 3 weeks. All data of 552 patients were available at follow-up after 6 weeks of treatment. The subjective improvement in symptoms of stress urinary incontinence (SUI) was 82% for grade 1, 77% for grade 2, and 69% for grade 3. Voluntary urinary control and symptoms of urgency were improved in more than 80% of patients. Frequency was reduced in almost 50%. Compared with conditions at the outset of the study, after 6 weeks, vaginal lubrication is normal in 77%, and intercourse is no longer painful for 88%. Objective parameters were: no change in existing descent of the anterior vaginal wall, and normal cytoscopic findings in 66% of the patients in whom these were previously pathologic. Vaginal atrophy improved in approximately 40% of cases. A quality of life score revealed improvement in 72%, no change in 20% and worsening in 9% of patients compared with conditions at the start of therapy. During therapy, symptoms worsened in 1%; 2% of patients suffered from the adverse effects, with vaginal itching and burning sensations. Our results confirm the value of topical estrogen application as a cornerstone of efficient treatment of stress and/or urge incontinence in the postmenopausal patient. PMID- 1462490 TI - Winter outbreaks of laminitis in dairy calves: aetiology and laboratory, radiological and pathological findings. AB - During the winter months of 1984 to 1989, outbreaks of laminitis occurred in up to 6 per cent of all the dairy calves aged four to six months on a dairy farm in a village in Israel. The clinical signs were reluctance to move, an arched back, overgrown hooves, supracoronary swelling and occasional walking on the carpus; most of the calves were unthrifty. Owing to the regular recurrence of the disease, the feeding and haematological, radiological and pathological changes in both the affected and normal calves at the farm, and in normal calves at another farm in the same village were studied. In the affected calves there were significant increases in serum protein concentration and in the activities of creatine phosphotinase and gamma-glutamyltransferase. Radiography showed dilated PIII vascular channels and some PIII rotation. Post mortem studies revealed haemorrhages in the laminar section of the hoof. The management of the farms differed in the protein level of the milk replacer and the 'starter' diet used during the first few months. The affected farm used feeds containing 18 per cent digestible protein whereas the unaffected farm used feeds containing 15.3 per cent digestible protein. PMID- 1462491 TI - Actinobacillosis in bovine caesarean sections. AB - An infection with Actinobacillus lignieresii, which was spread by a veterinary surgeon, caused problems after caesarean sections in cows on several farms. The wounds became hard about six weeks after the operation, and a few weeks later small abscesses developed and later the wounds were covered with small and large granulomas. The general health of about 20 per cent of the affected cows was poor and in these cows multiple granulomas could be detected in the abdomen by rectal palpation. PMID- 1462493 TI - Update on the incidence of summer mastitis in England and Wales. PMID- 1462492 TI - Urethral leiomyoma causing post renal failure in a bitch. PMID- 1462494 TI - Positioning of identification transponders in the auricle of pigs. PMID- 1462495 TI - Serological response of turkeys to the intravaginal inoculation of Mycoplasma iowae. PMID- 1462496 TI - Chyloperitoneum associated with torsion of the large colon in a horse. PMID- 1462497 TI - Cannibalism in laying hens. PMID- 1462498 TI - [A novel study of the metabolism of niacin and nicotinamide coenzymes]. PMID- 1462499 TI - [Medicinal means of metabolic therapy based on vitamins and coenzymes (review)]. PMID- 1462500 TI - [Bioantioxidants--required nutritional factors]. PMID- 1462501 TI - [Antioxidant properties of vitamins and their complex with blood proteins]. PMID- 1462503 TI - [Metabolism of vitamins and their use in ischemic heart disease]. PMID- 1462502 TI - [Excretion of vitamins and their metabolites in urine as criteria of human vitamin status]. PMID- 1462504 TI - [Immunomodulating and anticarcinogenic activity of carotenoids]. PMID- 1462505 TI - [Nicotinamide coenzymes in the regulation of cellular metabolism in various types of diabetes]. AB - Hypoglycemic and hypolipidemic effects of nicotinamide in insulin-dependent and noninsulin-dependent types of diabetes have been investigated. Hypoglycemic effect of nicotinamide in alloxan- and streptozotocin-induced diabetes resulted in activation of NAD+ biosynthesis and corresponding alterations in the redox state of free nicotinamide coenzymes. Increase in the free NAD+/NADH ratio was accompanied by inhibition of key gluconeogenic enzymes and by a decrease in the rate of 2-14C-incorporation into glucose in liver tissue and by inhibition of sorbitol formation in lens tissue. Nicotinamide exhibited hypolipidemic effect in db/db mice with noninsulin-dependent diabetes. The agent inhibited the enzyme of primary steps of lipogenesis, altered the structure of intercellular CoA pool and lowered the rate of lipid biosynthesis in liver tissue, thus normalizing blood lipoprotein compositions. PMID- 1462506 TI - [Impaired metabolism of vitamin D and use of its metabolites in chronic kidney diseases in children]. PMID- 1462507 TI - [Experimental basis for the use of vitamins in the multimodal treatment of stomatological diseases]. AB - The "Aerovit" vitamin complex prevents metabolic acidosis development and increased the rate of oxidation in tissues, which is accompanied by predominance of oxidized metabolites of glycolysis and Krebs cycles, by activation of their key enzymes as well as by an increase in the ratio of SH/SS-groups in water soluble protein and low molecular weight fractions, by a decrease in activity of lipase. At the same time, patterns of acid-alkaline equilibrium were normalized in blood. Preventive effect of the vitamin complex was noted in treatment of the diseases accompanied by acidosis; in parodontitis the vitamins suppressed the atrophy of maxillary alveolar bone structures, normalized the acid-alkaline equilibrium in blood and decreased the rate of metabolic acidosis in liver and bone tissues. PMID- 1462508 TI - [The biological effectiveness of the proteins in the specialized product "Ovolact" in the nutrition of patients following reconstructive surgery on jaw bones with congenital deformities]. AB - Postoperative feeding with a special-purpose foodstuff Ovolact proved superior to tube feeding in patients on after treatment following surgical correction of congenital jaw defects. This was evident from assessment of anthropometric and protein metabolism parameters. Nitrogen metabolism underwent positive changes reflecting the product value for maintenance of protein status of the above patients. Therefore, Ovolact can make more effective postoperative rehabilitation in jaw reconstruction. PMID- 1462509 TI - [Tube feeding of patients with cancer of the larynx in the early postoperative period]. PMID- 1462510 TI - [Seasonal dynamics of the indices of humoral immunity in children aged 3 months to 1 year in relation to nutrition in an arid zone]. AB - The paper reports seasonal data on humoral immunity of 245 Turkmen and 240 European infants aged 3-12 months. Allowances were made for climatic conditions of the arid zone and essential feeding. In summer there were reduced levels of IgM, IgG in the serum and insufficient supply with thiamine and ascorbic acid. IgA serum level was the lowest in spring. IgA strongly correlated (r = 0.7-0.8) with thiamine and ascorbic acid intake in spring, IgM and IgG with retinol and thiamine in summer. The above changes in humoral immunity in summer are associated with growing incidence of intestinal diseases and lower body mass in the infants in the condition of arid zone. PMID- 1462511 TI - [Polyvitaminization--an effective method of optimizing the vitamin status of children]. AB - Insufficient vitamin value of the food rations for children at nurseries is expressed in lowered levels of vitamins and their metabolites in the urine, as well as in a higher frequency of vitamin and, particularly, polyvitamin deficiency in children, especially, in the winter-spring period. Improvement of the quality and increasing the quantity of food, prophylactic administration of polyvitamins in the periods of higher vitamin deficiency would be effective and real ways for optimization of vitamin status of children. Dragee "Undevitum" and "Hexavitum" proved to be most effective among the prophylactic polyvitamins, the synergy of action of their components provides the improvement in the values of renal excretion of vitamins and their metabolites, as well as reduction in the frequency of micro-symptoms of polyvitamin deficiency. PMID- 1462513 TI - [The status of the actual nutrition of pregnant women in an epidemically unfavorable region of Kazakhstan]. AB - Questionnaire survey and body mass control followed by computer estimation of the diet chemical composition were conducted in 30 pregnant women in summer and autumn. Deficiency in intake of meat products, vegetable oil, potatoes reached 15.2-34.7, 24.2-55.8, 55-65.7%, respectively, in the trimester I and II. The dietary lack of fish, eggs, vegetables, fruit could be hardly compensated by bakery foods and sweets. Protein deficiency rose to 25-38.3%, that of fat 19.1 25.2%. Intake of carbohydrates was satisfactory, though mineral salts and vitamins were provided incompletely. PMID- 1462512 TI - [The provision of vitamins to school children in rural regions of Lithuania]. AB - Providing with vitamins of schoolchildren was studied in some regions of Lithuania during the winter-spring period. The biochemical blood count has revealed insufficient providing of schoolchildren with ascorbic acid, beta carotene, vitamins B1, B2 and B6. Decreased levels of ascorbic acid in urine, as well as micro-symptoms of hypovitaminosis (ascorbic acid, thiamine and riboflavine deficiencies) have been recorded. PMID- 1462514 TI - [The iron deficiency status and the actual nutrition of women in Gorno-Altai]. AB - Standard methods (questionnaires, peripheral blood count, iron pool) were employed to study epidemiology (prevalence and risk factors) of iron deficiency in the women of the Altai mountains and the relation of this deficiency with essential nutrition. Hemoglobin dispersion was found to depend on fuel value of the ration, total protein levels, polyunsaturated fatty acid content. PMID- 1462515 TI - [The present nutrition of workers in the mining industry]. PMID- 1462516 TI - [The selenium content of food products and the blood of inhabitants of Norilsk]. AB - The intake of trace element selenium by Norilsk citizens was assessed by its levels in the serum, food and soil. It was found that soil and food made in the Norilsk region are rich in selenium, its serum concentration in the population is normal (102 micrograms/l). References to such values for the Moscow and Zaporoje (Ukraine) regions are made. Low selenium levels in the serum may be indicative of pulmonary diseases. PMID- 1462517 TI - [The effect of ascorbic acid supplements on the anti-infection resistance of the body]. PMID- 1462518 TI - [The effect of water-soluble sorbents on the exocrine function of the liver]. AB - The effect of water-soluble sorbents on exocrine function of the liver was studied in chronic experiments on 2 dogs with a brought out bile duct. It is shown that choline and digitonin sorbents exhibit choleretic properties similar to those of cholestyramine. Choline sorbent causes a drop in the concentration of (2-4-fold) cholic acid in the bile unlike digitonin sorbent. No prolonging action was seen upon cholestyramine administration, while choline sorbent do demonstrate it. Cholesterol and bilirubin levels do not respond noticeably to the above sorbents. PMID- 1462519 TI - [The effect of the zinc content in the rations of experimental animals on the absorption, distribution and accumulation of cadmium chloride in the body with different methods of administration]. AB - Intravenous (20 kBk) and intragastric (400 kBk) cadmium chloride administration to 45 white noninbred rat males kept for a month on a semisynthetic isocaloric diet including 0.0005 and 0.001% zinc were evaluated for absorption and distribution. Radionuclide findings provided the conclusions that: the absence or excess of zinc in the diet stimulates cadmium absorption from gastrointestinal tract; cadmium distribution in the viscera (the liver, kidneys, pancreas) varies with route of entry, the least accumulation of oral cadmium in the above viscera is observed in animals receiving optimal zinc quantities. PMID- 1462520 TI - [The effect of nutritional factors on lipid peroxidation in the microsomes of rats of varying ages]. AB - 5-month- (mature) and 24-month-old (old) male Wag rats were examined for lipid peroxidation products and antioxidant enzymes activity in the liver cytosol. Imbalanced rations are shown to contribute to enhancement of lipid peroxidation entailing accumulation of lipid peroxidation products and inhibition of antioxidant enzymatic activity. Enrichment of food with antioxidant vitamins and fibers leads to lowering of age-related peroxidation. PMID- 1462521 TI - [The effect of the composition of food rations on the free amino acid content and the indices of the acid-base balance in the blood during aging]. AB - In experiments on aging rats fed 5 different rations by protein, tryptophan, prevailing base or acid equivalents it was found that tryptophan and plant protein deficiency, high levels of acid equivalents affect serum amino acid composition, aggravates acidosis. Restriction of basic food substances intake in parallel with prevalence of base equivalents made amino acid pool optimal, increased base serum reserves and contributed to longer life-span. PMID- 1462522 TI - [Essential fatty acids in the prevention and treatment of vascular complications of diabetes mellitus]. PMID- 1462523 TI - [The effect of protein-calorie food deficiency on the activity of enteral enzymes in growing rats]. AB - 30-day changes in enteral enzymes were followed up in test and control growing white rats. Test animals received protein- and calorie-deficient feeding. It was established that retardation of growth was more marked in protein than in calorie deficiency. PMID- 1462524 TI - [Experimental evaluation of the allergen activity of a peptide preparation produced from an enzymatic hydrolysate of milk proteins using ultrafiltration]. AB - Noninbred guinea-pig experiments were performed to investigate specific potential allergenicity of cow milk proteins (CMP) consisting of casein (80%) and serum proteins (20%), of low-molecular peptides (LMP 20/80) produced from CMP 20/80 by enzymatic hydrolysis and ultrafiltration; to evaluate nonspecific effect of test diet CMP 20/80 and LMP 20/80 on anaphylactic response of the animals to ovalbumin and histamine LD50. LMP 20/80 versus CMP 20/80 had a hypoallergenic effect. Potential mechanisms of low anaphylactic sensitivity induced by LMP 20/80 are discussed. PMID- 1462525 TI - [A comparison of methods of determining 4-pyridoxic acid in urine]. AB - Routine fluorescent assays for urine 4-pyridoxic acid (4-PA) in variants of lactone 4-PA external standard (variant 1) and internal 4-PA standard (variant 2) were compared to high performance liquid chromatography. Correlation between the two values were defined by specially derived equation. The internal standard is preferable, as variant 1 presents underestimated results. Variant 2 is limited to high 4-PA concentrations, being unfit in low ones for overestimating the data. The chromatography proved most reliable and specific. PMID- 1462526 TI - [The effect of storage conditions on the amino acid composition of champignons]. PMID- 1462527 TI - [The chemical composition of national products from horseflesh]. PMID- 1462528 TI - [The vitamin and microelement content of rarely cultivated vegetables in the Cis Urals]. PMID- 1462529 TI - [New developments in methods of dietetic therapy of patients with hypertension]. PMID- 1462530 TI - Caring for hearing-impaired patients in compliance with the Americans With Disabilities Act. PMID- 1462531 TI - The Breast Cancer Prevention Trial (BCPT) in West Virginia. AB - Female breast cancer is a major medical problem with significant public health ramifications. During the next decade, more than 1.5 million women in the United States will be newly diagnosed with invasive breast cancer. The Breast Cancer Prevention Trial (BCPT) is an NIH-sponsored study which will determine whether long-term tamoxifen therapy is effective in: 1) Preventing invasive breast cancer, 2) Lowering the incidence of fatal and nonfatal myocardial infarction, and 3) Reducing the incidence of bone fractures. Sixteen thousand women, including at least 100 from West Virginia who are > or = 35 years of age at increased risk for breast cancer, will be randomized between placebo and tamoxifen during a two-year period. For each participant, the annual and lifetime probability of developing breast cancer will be estimated utilizing a computerized model of risk assessment. The placebo or tamoxifen will be administered for at least five years. Toxicity, compliance, monitoring of quality of-life assessment, and lipid and lipoprotein evaluations are major components of this trial. PMID- 1462532 TI - Cardiopulmonary arrest in pregnancy: the role of caesarean section in the resuscitative protocol. AB - A 36-year-old black multipara at 32 weeks gestation was referred with apparent peripartal cardiomyopathy. Upon arrival, she was found to be in pulmonary edema; and shortly thereafter developed cardiopulmonary arrest. She failed to respond to initial attempts at cardiopulmonary resuscitation but subsequently responded after Caesarean section and pericardiocentesis. This case exemplifies the unique aspects of performing cardiopulmonary resuscitation on a gravid female in the latter part of pregnancy and that Caesarean section should be considered an integral part of the resuscitative protocol when standard protocols fail. PMID- 1462533 TI - Efficacious treatment of the common wart (verruca vulgaris). AB - A relatively benign lesion, the common wart (verruca vulgaris), probably occurs sometime during the lifetime of most individuals. Since it is usually self limited, it may attract little attention unless it appears on the sole of the foot, adjacent to a fingernail or toenail, or somewhere on the face. Anyone with a serious interest in the etiology of the wart is directed to the many excellent works on this and related viral lesions. The purpose of this paper is to tell of one doctor's search for a reasonable, non-surgical, non-invasive treatment that would be acceptable to most patients. PMID- 1462534 TI - To save health care dollars. PMID- 1462537 TI - Controlling a syphilis epidemic. AB - In 1986 the rate of infectious syphilis (primary and secondary) in Los Angeles County began to rise from previously stable levels of about 23.5 per 100,000 to peak at 55.6 per 100,000 in 1987. The incidence of congenital syphilis increased from 205 cases in 1987 to 575 cases in 1989. The county's Sexually Transmitted Disease Program instituted a disease-specific plan to address the epidemic. Factors considered in designing the program included the high morbidity and mortality associated with congenital infection, the existence of latent infection, self-limiting symptoms, and the availability of an inexpensive screening test and curative treatment. Policy changes implemented comprised expanded screening, expanded surveillance, increased contact tracing, and the initiation of condom promotion programs. To evaluate the relative effectiveness of Los Angeles County's syphilis control efforts, the epidemic curve for infectious syphilis was compared with trends in other urban areas. Although the rate of infectious syphilis climbed a year earlier in Los Angeles than in other cities, it returned to baseline levels when other cities' rates remained at epidemic levels. PMID- 1462535 TI - Tuberculosis chemoprophylaxis. AB - The incidence of tuberculosis in the United States, after decreasing for many years, has recently begun to climb at an alarming rate. This rise is due mainly to excess cases in high-risk groups including human immunodeficiency virus infected patients, the elderly, the foreign born, and the homeless. In the United States tuberculosis has been associated with a 10% mortality despite adequate treatment. The tuberculin skin test is a safe and inexpensive test for detecting tuberculous infection. To improve its predictive value the diagnostic criteria for classifying a positive reaction have recently been revised. High-risk populations should be screened to identify those persons who would most benefit from preventive treatment. Isoniazid therapy taken for 6 to 12 months is a safe and highly effective means of preventing tuberculous infection from developing into active disease. The most worrisome toxicity of isoniazid, fatal hepatitis, is extremely rare; when patients are monitored closely the incidence of death from hepatotoxicity is less than 0.01%. PMID- 1462536 TI - The 10-year experience of an academically affiliated occupational and environmental medicine clinic. AB - Occupational and environmental diseases are underrecognized. Among the barriers to the successful diagnosis, treatment, and prevention of these conditions are inadequate consultative and information resources. We describe the 10-year clinical and training experiences of an academically affiliated referral center that has as its primary goal the identification of work-related and other environmental diseases. The University of Washington Occupational and Environmental Medicine Program has evaluated 6,048 patients in its diagnostic and screening clinics. Among the 2,841 seen in the diagnostic clinics, 1,553 (55%) had a work-related condition. The most prevalent diagnoses included asbestos related lung disease (n = 603), toxic encephalopathy (n = 160), asthma (n = 119), other specific respiratory conditions (n = 197), carpal tunnel syndrome (n = 86), and dermatitis (n = 82). The clinics serve as a training site for fellows in the specialty training program, primary care internal medicine residents, residents from other medical specialties, and students in industrial hygiene, toxicology, and occupational health nursing. The program serves two additional important functions: providing consultative services to community physicians and training specialists and other physicians in this underserved area of medicine. PMID- 1462538 TI - Predicting risk for medical malpractice claims using quality-of-care characteristics. AB - The current fault-based tort system assumes that claims made against physicians are inversely related to the quality of care they provide. In this study we identified physician characteristics associated with elements of medical care that make physicians vulnerable to malpractice claims. A sample of physicians (n = 248) thought to be at high or low risk for claims was surveyed on various personal and professional characteristics. Statistical analysis showed that 9 characteristics predicted risk group. High risk was associated with increased age, surgical specialty, emergency department coverage, increased days away from practice, and the feeling that the litigation climate was "unfair." Low risk was associated with scheduling enough time to talk with patients, answering patients' telephone calls directly, feeling "satisfied" with practice arrangements, and acknowledging greater emotional distress. Prediction was more accurate for physicians in practice 15 years or less. We conclude that a relationship exists between a history of malpractice claims and selected physician characteristics. PMID- 1462540 TI - Photorefractive keratectomy. PMID- 1462539 TI - Gastrointestinal complications of nonsteroidal anti-inflammatory drugs. AB - Nonsteroidal anti-inflammatory drugs have become increasingly popular, with more than 90 million prescriptions being written annually. These drugs inhibit the intracellular cyclooxygenase enzyme system, thus blocking the production of various prostaglandin compounds. This, in turn, interferes with normal mucosal protective mechanisms, leading to local injury. Gastrointestinal complications of nonsteroidal anti-inflammatory drug use include ulcerations, hemorrhage, perforation, stricture formation, and the exacerbation of inflammatory bowel disease. Treatment involves stopping the drug if at all possible and then instituting more specific therapy depending on the anatomic area that has been injured. PMID- 1462541 TI - Macular surgery. PMID- 1462542 TI - Laser treatment of diabetic retinopathy. PMID- 1462543 TI - Retinitis pigmentosa--new advances in ophthalmic genetics. PMID- 1462544 TI - Current therapy for disorders of the optic nerve. PMID- 1462545 TI - Graves' ophthalmopathy. PMID- 1462546 TI - Small-incision cataract operation. PMID- 1462548 TI - Isolation of Borrelia burgdorferi from ticks in southern California. PMID- 1462547 TI - Maternal death due to rupture of a low transverse cesarean section incision during labor at home. PMID- 1462549 TI - Personal renewal. AB - After John Gardner's presentation on "Self-Renewal" to THE WESTERN JOURNAL OF MEDICINE Editors' Meeting, (*) Joseph Murphy, MD, Special Editor for Wyoming, asked the former Secretary of Health, Education, and Welfare, "Where are you in your life's cycle?" Dr Gardner, who is 80 years old, answered, "When Chief Justice Oliver Wendell Holmes, Jr, was in his 90s, he was asked a similar question and said, ;I'm like a race horse cantering along after the race is over, cooling down.' Well, I'm nowhere near cantering! I'm still in the race, pushing the world." race, pushing the world."John Gardner, who received his undergraduate degree from Stanford and PhD from the University of California, Berkeley, taught at the college level for several years before he joined the Carnegie Foundation. As president of Carnegie Corporation and Carnegie Foundation for the Advancement of Teaching, he began to "push the world" toward education and in 1964 received the country's highest civilian honor, the Presidential Medal of Freedom. He has also pushed it toward political reform by founding Common Cause, toward grass roots political action by founding the Urban Coalition, toward leadership training by founding the White House Fellows program, and toward volunteerism by founding the Independent Sector (a coalition of for-profit and not-for-profit organizations and foundations). His books, including Excellence, Self-Renewal, No Easy Victories, and On Leadership, have pushed readers to new understanding of themselves and of organizations to higher levels of creativity and energy to get important work done. His current research focuses on discovering and defining the characteristics of healthy, vital communities. His call to "keep on keeping on," indeed, to push the world, leads to constructive change. Active people become effective people, infused with the energy and optimism that good hard work inspires. I think you will find this paper as invigorating to read as it was to hear. PMID- 1462550 TI - 'New habits of mind'--bridging the gap between public health and clinical medicine. PMID- 1462551 TI - Complications of asplenia and hyposplenism--persistent uncertainties. PMID- 1462552 TI - Treatment strategies in the prevention of tuberculosis. PMID- 1462553 TI - Nonsteroidal anti-inflammatory drugs and ulcers. PMID- 1462554 TI - 'What kind of work do you do?'. PMID- 1462555 TI - Cancer screening in women. PMID- 1462556 TI - Exaggerated threat of childhood lead poisoning in California--epidemic by edict. PMID- 1462557 TI - Another health food hazard--gamma-hydroxybutyrate-induced seizures. PMID- 1462558 TI - Licensing of tissue banks in California. PMID- 1462559 TI - Pulse oximeter versus electrocardiogram. PMID- 1462560 TI - Discounting our future. PMID- 1462561 TI - Meta-analyses revisited. PMID- 1462562 TI - [Biochemical indicators of the nutritional status of the body in various diseases of the digestive system]. AB - In 45 patients with chronic digestive tract diseases (gastric and/or duodenal peptic ulcer, cholecystolithiasis, conditions after gastrectomy and cholecystectomy) the biochemical parameters serving as indicators of the nutritional status of the organism (Hb, Bc, Fe, Ca, alkaline phosphatase) were determined. In the group with postgastrectomy syndrome the serum calcium level was decreased. The other parameters were normal in all groups of patients. PMID- 1462563 TI - [Appendicitis and its atypical causes]. AB - The authors analysed 2849 patients who were admitted to the Department of General Surgery, Regional Hospital in Pisz in the years 1980-1989 with symptoms suggestive of appendicitis. In 983 cases surgical intervention was abandoned, because the symptoms regressed spontaneously or were caused by diseases of other organs. The pathological conditions associated with appendicitis are analysed in 1866 surgically treated patients. Cases of appendicitis caused by Oxyuris vermicularis, Salmonella-enteritidis and actinomycosis (one case each) and appendicular carcinoma (2 cases) are described in more detail. Attention is called to the aetiology, pathogenesis and treatment of these rare causes of appendicitis. PMID- 1462564 TI - [Cigarette smoking as a risk factor of premature labor]. AB - The effect of cigarette smoking by parents on the incidence of premature labour was analysed. Premature labours accounted for 14.1% of all labours. Cigarette smoking by pregnant women was a significant risk factors for prematurity, it increased significantly hypoxia caused by chemical pollution of the environment and contributed to intrauterine hypotrophy in premature babies. The per cent of smokers among premature babies with normal weight was 37.4%, but among premature babies with the syndrome of intrauterine hypotrophy it was 58.4%. The per cent of heavy smokers was significantly in the group of premature babies, and also the duration of smoking habit by mothers was longer. PMID- 1462565 TI - [Acute appendicitis in pregnancy]. AB - A retrospective analysis is reported of 110 pregnant women with acute appendicitis on the basis of inquiry with participation of 23 surgical centres in the period 1979-1989. Attention is called mainly to diagnostic difficulties and peculiarities of the clinical course of this acute abdomen syndrome in pregnancy. The authors found that acute appendicitis was most frequent in primiparae in the 1st and 2nd trimester of pregnancy and the always high mortality was caused mainly to delay of operation. PMID- 1462566 TI - [Evaluation of N-acetyl-beta-D-glucosaminidase (NAG) and its isoenzyme activities in the urine of children with primary and secondary hypertension]. AB - The total activity of N-acetyl-beta-D-glucosaminidase (NAG) and its isoenzymes A and B was determined in the urine of 18 children aged 9-18 years with essential hypertension and 21 with nephrogenic hypertension. The results were compared with those in a control group of 30 healthy children. The obtained results show that in children with stabilized hypertension (above the 95 centile) of essential type the proportion (above the 95 centile) of essential type the proportion of urinary isoenzymes are changes, with higher activity of the B isoenzyme. On the other hand, in children with nephrogenic hypertension the total activity and the activity of the B isoenzyme are increased. After reduction of blood pressure following hypotensive treatment (below the 90th centile) the activity of NAG and its isoenzymes was again normal in essential hypertension and was much reduced in nephrogenic hypertension. The study demonstrated that hypertension leads to transient damage to the proximal tubules which is reversed by effective hypotensive treatment. PMID- 1462567 TI - [Mediastinal infiltration in children with acute lymphoblastic leukemia]. AB - The clinical and haematological analysis is presented of six out of 68 cases of acute lymphoblastic leukaemia in children. In these six cases mediastinal involvement was found. They accounted for 8.8% of all patients and all were boys aged over 4 years. In all these cases the course was dramatic, with high risk and with signs of poor prognosis: infiltration of organs, very high leucocyte counts. T-cell blasts. The evident clinical uniformity of the symptoms and laboratory similarity of these cases suggest that they should be isolated as a separate subgroup, and therapeutic failures observed as yet indicate the necessity of caution in prognosis. PMID- 1462568 TI - [The role of phospholipase A2 in acute pancreatitis]. PMID- 1462569 TI - [Chorionic biopsy--a new trend in prenatal diagnosis]. PMID- 1462570 TI - [Lyme disease--also a childhood disease]. AB - In the light of a survey of the world literature Lyme borreliosis, an epidemic disease caused by gram-negative organisms Borrelia burgdorferi is described. The disease has three phases with involvement of the skin, the nervous system, the cardiovascular system and joints. Treatment with antibiotics is effective. The disease lies in the fields of interest of various specialties including paediatrics. PMID- 1462571 TI - [Etiology, pathomechanism and therapy of Dupuytren's contracture]. PMID- 1462572 TI - [Controversies regarding the use of 0.75% bupivacaine]. AB - Controversies are described regarding wide introduction of bupivacaine with raised concentration (0.75%) of the active components, which has been introduced in other countries in the strongest local anaesthetic agent used as yet but in early 1980s it has been withdrawn from several western countries in view of possible serious cardiovascular side effects. Presently, after a number of studies it been demonstrated that these suppositions were unfounded and the observed complication were due errors in anaesthesiological techniques and not to an exceptional cardiotoxicity of the drug. PMID- 1462573 TI - [A case of histiocytosis X complicated by recurrent spontaneous pneumothorax]. AB - A rare case of the generalized of histiocytosis X is described. Due to pulmonary involvement the disease was complicated by three episodes of spontaneous pneumothorax. PMID- 1462574 TI - [A case of nephrotic syndrome in chronic glomerulonephritis with coexistent diffuse thrombophlebitis]. AB - A case is described of nephrotic syndrome with coexistent thrombosis of the splenic vein and the common iliac veins. The possible pathological mechanism of tge disease and the therapeutic and diagnostic difficulties during this disease superimposed upon chronic glomerulonephritis are discussed. PMID- 1462575 TI - [A case of bilateral acoustic neuroma in a 19-year-old girl]. AB - A rare case of bilateral neurinoma of the acoustic nerve is described. The patient was a girl aged 19 years without external evidence of von Recklingshausen disease. PMID- 1462576 TI - [Acute encephalopathy in ethylene glycol poisoning]. AB - Poisoning with ethylene glycol is the most frequent poisoning in our country. Acute encephalopathy during this poisoning may be a cause of important diagnostic difficulties, especially in the initial phase of the poisoning, due to the variety of symptoms and signs. Three cases of this poisoning are reported. All patients were erroneously referred and admitted to neurological hospital department. It is postulated that in each case of coma of unknown aetiology with signs suggesting damage to the brain stem and hyperventilation arterial blood gasometric examination should be done and blood and urine should be taken for toxicological investigations. In the treatment of glycol poisoning the most important task is to correct metabolic acidosis and to apply early dialysis treatment in serious intoxication. PMID- 1462577 TI - [Intravenous rehydration in acute diarrhea in children. I. Theoretical considerations]. PMID- 1462578 TI - [Intravenous rehydration in acute diarrhea in children. II. Clinical experience]. PMID- 1462579 TI - [Medical advice for king Jan III Sobieski]. PMID- 1462580 TI - [18th century description of malaria]. PMID- 1462581 TI - [Evaluation of the effectiveness of delayed-action propranolol in the treatment of arterial hypertension]. AB - The reported study was carried out in 25 patients aged 21 to 58 years with essential hypertension in second stage of WHO classification. During three months in 10-day courses they were given alternately 1 placebo tablet or 160 mg propranolol retard in one dose daily. The values of the heart rate and blood pressure were compared before and after the treatment. A significant decrease of systolic and diastolic blood pressure and heart rate was noted. The comparison of blood pressure and heart rate values after 10 days on propranolol with those before the treatment showed a statistically significant reduction of these parameters. This is an evidence that the hypotensive action of propranolol retard develops already during 10 days of treatment. PMID- 1462582 TI - [Diagnostic difficulties in pleural mesothelioma]. AB - The analysis is reported of 29 case records of patients admitted in the last 25 years to the Department of Pulmonary Diseases and Tuberculosis, Medical Academy in Gdansk with suspected pleural malignant mesothelioma. In 16 cases the diagnosis was confirmed by histological examination, and in 13 cases the diagnosis of mesothelioma was based on the whole clinical picture and cytological examination of pleural effusion. The most frequent symptoms included dyspnoea, pain, progressing weakness. In most cases signs of increasing effusion volume and sometimes also of pleural thickening were found on medical and radiological examination. The mean survival time was 5 months. The results of treatment were not satisfactory. PMID- 1462583 TI - [Epidemiology of cholelithiasis among professionally active persons in the Katowice province]. AB - In the workplaces of the City of Katowice 2867 subjects in 5 age groups were studied by inquiry, physical examination and gallbladder ultrasonography. Calculi in the gallbladder were found in 344 subjects that is 11.99%. The prevalence of calculi was much higher in females, and in both sexes it increased with age. The study confirms the value of USG in the diagnosis of gallbladder calculi and the possibility of its use for screening of the general population. PMID- 1462584 TI - [N-acetyl-beta-D-glucosaminidase and diurnal excretion of hydroxyproline in chronic viral hepatitis]. AB - In 37 patients with chronic active hepatitis, in 14 with chronic persistent hepatitis and in 11 with normal histological pattern of the liver the serum activity of N-acetyl-beta-glucosaminidase and the 24-hour excretion of hydroxyproline with urine were determined. The 24-hour excretion of hydroxyproline was similar in all groups of patients, while the activity hepatitis and higher than in those of chronic persistent hepatitis (36.9 +/- 12.9 i.u. per 100 ml versus 22.4 +/- 8.2 i.u. per 100 ml, p less than 0.05). In patients with high serum NAGL activity cirrhosis developed significantly more frequently. PMID- 1462585 TI - [Dynamics of the changes in insulin requirement during the treatment with biosynthetic human insulin]. AB - In 20 patients treated previously with porcine insulin human recombined insulin Eli Lilly was tried. During one year of its use under strict therapeutic conditions a significant decrease of the requirement for insulin was achieved, especially in the first three months of the trial, especially in patients with shorter duration of diabetes. At the same time, carbohydrate metabolism improved significantly. No side effects of the new insulin were noted. PMID- 1462586 TI - [Microbiological evaluation of the effectiveness of gynalgin in the treatment of vaginitis]. AB - The microbiological effectiveness of the preparation Gynalgin produced by POLFA Pharmaceutical Works in Rzeszow was assessed in cases of vulvovaginitis in 55 patients with clinically diagnosed inflammatory conditions of the lower genital tract, who were given Gynalgin tablets in 10-day courses. Vaginal smears were examined three times for the presence of bacteria, fungi and trichomonas vaginalis (before and immediately after the treatment, and two weeks later). In the initial examination in five vaginal smears mixed bacterial flora was found, in 6 smears trichomonas was present, in 4--bacteria and fungi, and in one- trichomonas and fungi. After the treatment in control examinations I and II the number of the isolated bacterial strains was lower, trichomonas was no longer present, and the number of fungi was reduced evidently. In the light of these microbiological examinations Gynalgin was found to exert a strong fungicidal, bactericidal and antitrichomonal activity, and the results of laboratory investigations agreed with those of clinical trials of Gynalgin effectiveness. PMID- 1462587 TI - [Thrombocytopenia in newborn infants caused by autoimmune thrombocytopenic purpura in their mothers]. AB - Five cases of congenital thrombocytopenia caused by immunological thrombocytopenia in mothers are presented. In one newborn whose mother had normal platelet count after splenectomy performed for ITP transient congenital thrombocytopenia was observed after birth. One child died due to intracranial hemorrhage. Practical conclusions are presented with regard to the diagnosis and management of neonatal thrombocytopenia caused by maternal ITP, and prophylactic management is suggested to prevent the complications of neonatal thrombocytopenia in case of maternal ITP. PMID- 1462588 TI - [Evaluation of physical fitness of children with mitral valve prolapse into the left heart atrium]. AB - Effort tolerance was assessed in 25 children with idiopathic syndrome of mitral valve leaflet prolapse into the left atrium. The children were aged 9 to 15 years. The results of the ergometric test confirmed the clinical observations suggesting that children with the syndrome tolerate exercise as well as their healthy peers. PMID- 1462589 TI - [The so-called stroke headache]. AB - Sudden violent headache occurring for the first time in life suggests subarachnoid haemorrhage and requires diagnostic management. In 20 cases the authors failed to find blood in cerebrospinal fluid, but in 8 cases the protein level was raised. The patients were examined again after 2-10 years, and had control neurological examination and CT of the brain. In half the cases similar headaches returned after various time periods, and haemorrhage was again ruled out. In all patient chronic headaches of lower intensity developed. Control CT examination showed in 7 cases scars or atrophy of brain tissue. It is difficult to qualify such headaches as migraine and other known types of headache. Recently in the literature a new name has been coined for them--thunderclap headaches, and some authors regard them as a sign of minor intracranial haemorrhage. CT changes, raised protein level in cerebrospinal fluid, and the type of pain may suggest haemorrhage. The usefulness of cerebral arteriography in such patients should be considered. We propose the name of stoke headache for suggesting the cause and special management. PMID- 1462590 TI - [Evaluation of glucose and cholesterol levels in the mother and newborn infant in the perinatal period]. AB - In 30 live born newborns the connections were assessed between glucose and cholesterol levels in umbilical cord blood after birth, and also in maternal blood before and two days after birth. Statistically significant differences of glucose and cholesterol levels were found between mothers and newborns in the perinatal period. Attention is called to greater independence of cholesterol (total, free and esterified) levels in newborn and mother in perinatal period. PMID- 1462591 TI - [Arterial hypertension and arrhythmia]. AB - In patients with hypertension and presence of left ventricular hypertrophy arrhythmias of ventricular origin occur more frequently than in hypertension without this hypertrophy. Ventricular arrhythmias predispose to sudden death. It is accepted presently that left ventricular hypertrophy in patients with hypertension should be regarded as an additional risk factor for sudden death. The use of hypotensive drugs reducing the mass of the myocardium may be justified. PMID- 1462592 TI - [Effects of histamine H2 receptor blockaders on the cardiovascular system]. PMID- 1462593 TI - [Viruses and bacteria in the etiology of acute respiratory tract infections in young children]. AB - Respiratory infections in small children are among the major problems in paediatrics. They are caused most frequently by viruses or bacteria. The role played by certain types of respiratory viruses in these infections is discussed, considering selected subgroups of children and the seasonal incidence of infections. The usefulness of certain virological investigations in clinical diagnosis is analysed. In the description of bacterial respiratory infections in small children attention is called also to certain bacteria belonging to opportunistic commensals and the importance of anaerobes. The main stress is laid on infections of newborns and infants which may be connected with the transfer of pathogens from mothers. Attention is called to the necessity of close monitoring of the aetiological factors of acute respiratory infections in the youngest children which could increase the accuracy of therapeutic management and prophylactic measures which should be regarded as a very important factor in the control of these infections. PMID- 1462594 TI - [Clinical picture of tuberculous peritonitis]. AB - The clinical picture of tuberculous peritonitis in productive form with formation of an abdominal tumour 18 x 20 cm in dimensions is described. The patient was a boy aged 19 years from rural environment. The diagnosis was based on bacteriological investigations, histological examination and clinical manifestations. Attention is called to diagnostic difficulties in cases of tuberculous peritonitis without positive tuberculin tests and with pulmonary fibronodular tuberculosis. PMID- 1462595 TI - [Congenital toxoplasmosis in a 6-week-old infant]. AB - A case of congenital toxoplasmosis was observed in an infant aged 6 weeks with fatal outcome. Histological changes produced by Toxoplasma gondii in the brain are described. PMID- 1462596 TI - [Steroid-resistant nephrotic syndrome in 2 children with milk protein intolerance]. AB - Two cases of steroid-resistant nephrotic syndrome with mesangial proliferation were observed in which prednisone treatment resulted in remission only after milk free diet. In both children intolerance to cow milk protein was demonstrated, and in one of them a family history of this intolerance was elicited. PMID- 1462597 TI - [Metastasis of penile cancer to the heart in a 20-year-old patient]. AB - A case of penile cancer was observed in a 20-year-old patient with very extensive remote metastases. On autopsy metastases were found to the heart and brain which are exceptionally rare in penile cancer. PMID- 1462598 TI - [A rare case of tuberculosis of the maxilla, zygomatic region, maxillary sinus and facial skin in a patient with diabetes mellitus]. AB - In an 82-year-old female diabetic tuberculosis involved the maxilla, zygomatic region, maxillary sinus and facial skin. No other foci of tuberculosis were found in the organism. The diagnosis and treatment are described stressing the extreme rarity of this involvement by tuberculosis. PMID- 1462599 TI - Women and sexually transmitted diseases. AB - This paper presents a brief review of historical developments in women's health care. It describes the current campaign against sexually transmitted diseases (STDs) and assesses the campaign's success in light of its history and the reality of women's lives. The authors suggest that women are forced into a double bind in which they are expected to take responsibility for the prevention of STDs although they may not have the ability to do so. Modifications are suggested which take into account gender-role socialization and social group norms. PMID- 1462601 TI - Sociodemographic correlates of alcohol consumption among African-American and white women. AB - Correlates of abstention and heavier drinking were examined among 654 African American and 474 white women, aged 19-70+, from a representative sample of households in Erie County, New York. Discriminant function analysis was employed to investigate the relationship between alcohol consumption and race, age, church attendance, family history of alcohol problems, household density, marriage, socioeconomic status (SES), employment and parity. Abstention was compared with drinking, and light/moderate drinking was compared with heavier drinking in the total sample and within each race. Compared to drinkers, abstainers were older, more religious, more likely to be African-American, or to be of lower SES. Racial differences in the correlates of abstention were found with respect to church attendance (positive association in African-Americans only), SES (negative association in African-Americans only), and household density (positive association in whites only). Compared to light/moderate drinkers, heavier drinking women were younger, less religious, more likely to be white, to have a positive family history, or to live in less crowded households. Racial differences in the correlates of heavier drinking were found with respect to church attendance (negative association in African-Americans only), parity (positive association in African-Americans only), and marital status (more heavier drinking among unmarried white women). Racial differences in the correlates of alcohol consumption document the need for further examination of the culture-specific determinants of women's drinking patterns. PMID- 1462602 TI - Secretaries, depression and absenteeism. AB - This study examines the prevalence of Major Depressive Disorder; missed work; and mental health services use among secretaries and other women employed full-time. In a random sample of 3,484 women employed full-time, women employed as secretaries were significantly more likely to be depressed than other women even after controlling for socio-demographic characteristics (odds ratio = 1.69, 95% confidence interval = 1.05, 2.73). Secretaries were significantly more likely to report missing work in the last three months (odds ratio = 1.77, confidence interval = 1.01, 3.11); a finding not attributable to depression. Secretaries were also more likely to seek mental health services, but this finding was not significant (odds ratio = 1.78, confidence interval = 0.55, 5.78). It is possible that these findings are attributable to a selection effect whereby depressed women, and women who are likely to miss work, become secretaries. A second possibility is that women employed as secretaries have more "nonwork role stress" than other employed women. Alternatively, job conditions which result in dissatisfaction and stress may lead to depression and absenteeism. We believe our findings warrant further investigation into the work environment of secretaries. PMID- 1462603 TI - Sexual exploitation in advertising health and wellness products. AB - This paper examines the way women are portrayed by the media in photographs advertising health and wellness products. Data were collected from five different health and fitness magazines. For purposes of this study, only advertisements in which women appeared were used in the analysis (N = 191). Findings suggest that a high percent of advertisements: (1) place women in submissive positions to men; (2) place women in unnatural poses; (3) emphasize dismemberment of body parts; (4) focus on sexuality rather than wellness. PMID- 1462604 TI - Primary care arrangements and access to care among African-American women in three Chicago communities. AB - African-American women of child-bearing age residing in three high-risk communities in Chicago were surveyed regarding their primary care arrangements and access to care (n = 552). This study examined factors which differentiated women who used office-based practices from those who used institutional settings (community clinics, health department clinics, hospital-based clinics) for primary care. Results of multivariate analysis indicate that women who used office-based practices were more likely than those who used institutional settings to see the same provider, to walk to their provider, to have less travel time and to walk in without an appointment. They were less likely to be hospitalized in the past year and less likely to report the availability of family planning at their usual source of care. Satisfaction with care, insurance status and sociodemographic characteristics were not associated with use of a particular facility type. Implications for organizing comprehensive health services for this population are discussed. PMID- 1462605 TI - WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty second report. PMID- 1462606 TI - The use of essential drugs. Model list of essential drugs (seventh list). Fifth report of the WHO Expert Committee. PMID- 1462607 TI - Recent advances in oral health. Report of a WHO Expert Committee. PMID- 1462608 TI - Surgical treatment of immune thrombocytopenic purpura. AB - The role of surgery in the treatment of immune thrombocytopenic purpura (ITP) is still discussed. The aim of this study was to verify our criteria of patient selection for splenectomy, to analyze the results of a protocol for the evaluation of the hemorrhagic risk, and to discuss long-term results of 70 patients with ITP who underwent surgical treatment from 1984 to 1990. All patients received steroid therapy. Sixty-two patients were given high doses of IgG (600 mg/kg/iv bolus) pre-operatively in order to obviate the need for intra operative platelet transfusions. Forty-three patients showed a significant increase in the platelet count, 8 a moderate increase, while 11 patients did not respond. No operative mortality was observed, however postoperative minor complications occurred in 14 (20%) patients. Accessory spleens were found in 11 (15.7%) patients. Mean follow-up was 21 months. Response to splenectomy was considered as complete (platelets greater than 150,000 mm3 with no need for medical treatment) in 63 (90%) patients. No response was observed in 7 patients. In 2 of the non-responders postoperative indium-111 scan revealed accessory spleens and ITP remitted after accessory splenectomy. All non-responders were in the group of patients who did not respond to the pre-operative infusion of high dose IgG. It can be concluded that splenectomy is a safe and effective treatment for ITP and that response to pre-operative infusion of IgG may be considered as predictive for the outcome after splenectomy. PMID- 1462609 TI - Small bowel anastomosis with the biofragmentable anastomosis ring and manual suture: a prospective, randomized study. AB - A total of 170 patients undergoing upper gastrointestinal surgery requiring a jejuno-jejunal enteroanastomosis were randomized into two groups according to the method to be employed at the enteroanastomosis. The most common procedures were partial gastrectomy for benign disease (84 patients), partial or total gastrectomy for malignant disease (35 patients), and bilioenteral bypass (31 patients, 25 for malignant disease). The enteroanastomosis was created by manual suture (3-0 Dexon, two layers) in 89 patients and with the Biofragmentable Anastomosis Ring (Valtrac-BAR) in 81 patients. Both end-to-side (101 patients) and side-to-side (69 patients) reconstructions were done. No ruptures or obstructions of the jejuno-jejunal anastomosis occurred. The postoperative recovery of the gastrointestinal tract was similar in the two groups in duration of nasogastric drainage, intravenous fluid therapy, and intestinal paralysis. Nor was there any difference between the groups in the duration of the postoperative hospital stay. Ten patients, 7 in suture-group and 3 in BAR-group, died postoperatively of causes unrelated to the enteroanastomosis. Thus the mortality rate was 7.9% in the suture group and 3.7% in the BAR group. The biofragmentable ring offers a safe alternative to manual sutures for small bowel anastomoses. PMID- 1462610 TI - Chondrosarcomas of the head and neck. AB - Chondrosarcomas of the head and neck are uncommon. Over a 35-year period (1950 1985) at our institution, 557 patients had an established diagnosis of chondrosarcoma. In 28 (5%) of these patients, the tumor was located in the head and neck region. A retrospective analysis was performed in an attempt to accurately define clinical characteristics, management, and outcome in these 28 patients. The patient population consisted of 15 males and 13 females whose ages ranged from 10 to 72 years, with a median of 38 years. Ten (36%) patients were untreated and 18 (64%) previously treated patients were referred for further management. The primary sites were maxilla (11), cervical vertebrae (7), mandible (3), skull (2), sphenoid and ethmoid sinuses (2), frontal sinus (1), nasal septum (1), and orbit (1). Lesions arising in the larynx were excluded from this study. The most common presenting symptom was a painless mass. Surgery was the definitive treatment in all patients. However, adjuvant radiation therapy or chemotherapy was utilized for residual disease in almost half of the cases (13 patients). Follow-up ranged from 5 to 35 years. Twelve (43%) of the 28 patients were known to be alive and free of disease more than 5 years after surgery. The most common cause of death was uncontrollable local disease (88%). However, only 3 of the 10 previously untreated patients developed local recurrence. For all patients, the median interval from time of first recurrence until death was 25 months (range 6 to 70 months). Positive margins in 8 of 12 patients resulted in local recurrence and eventual death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462611 TI - Surgical problems in octogenarians: epidemiological analysis of 1,083 consecutive admissions. AB - Patients older than 80 years of age are the most rapidly increasing group among surgical admissions and patients visiting emergency rooms. Epidemiological data of this group are of enormous medical and economic relevance. The principle aim of this study was to determine factors predictive of operative mortality in octagenarians, their clinical profiles, and length of stay compared to younger patients in similar diagnostic categories. A computer-based registry of geriatric surgery was used to record and analyze all relevant clinical and epidemiological data. The rate of admissions in octogenarians increased during the 18-year period (1973-1989) from 0.7% to 7.5% of all admissions. The number of patients undergoing surgery was 700. Three hundred and seventy-one of the procedures were elective and 329 were emergencies. Operations in octagenarians as a percentage of all operative procedures increased during the period considered from 1.1% to 5.1%. The operative mortality in this series was 10.5% prior to 1984 and decreased to 6% during the last 5 years. The average hospital stay of octagenarians was 9.8 days as opposed to 4.9 days in patients less than 70 years of age. The prognostic classification described by the authors proved very helpful in predicting mortality. PMID- 1462612 TI - The usefulness of tests in anorectal disease. AB - Specialized tests of anorectal function are designed to complement but not to replace good clinical examination and sound professional judgement. The different methods of recording pressure changes have advantages and disadvantages. Poor correlation exists when data recorded using miniature balloons are compared with data from microtransducers. Prolonged ambulatory monitoring of anal sphincter and rectal pressure reveal that spontaneous transient episodes of sphincter relaxation are demonstrable in normal subjects. In the investigation of patients with possible traction injury to the pudendal nerve, electromyography and pudendal nerve terminal motor latency data are more precise than manometry data. Good correlation between noninvasive surface electromyography using an intra-anal plug electrode and anal manometry can be attained. Mapping of sphincter defects using concentric needle technology is reasonably accurate but distinctly painful. Dynamic defecography readily demonstrates abnormalities of the rectal wall. The division between what is normal and what is clinically relevant is rather imprecise. Comparative studies of sonographic and electromyographic mapping of sphincter defects give good correlation. Recent application of fine hooked electrodes have demonstrated periodic episodes of smooth muscle and sphincter relaxation. The saline infusion test and balloon expulsion test help to accurately quantify the difficulty patients experience in retention or evacuation, respectively. Perineometry is a simple, rapid, noninvasive method of measuring the extent of perineal descent on straining. Although reproducible, it tends to underestimate the degree of descent when compared with the radiological method but it avoids the use of ionized radiation. PMID- 1462613 TI - Autonomic influences on colorectal motility and pelvic surgery. AB - The nervous control of the motility of the human distal bowel was investigated by two physiological studies of electrical stimulation of sacral parasympathetic outflow in patients with high spinal injuries and in patients with intractable constipation following pelvic surgery. Identical and reproducible motility responses of the left colon, rectum, and anal sphincters were obtained by sequential electrical stimulation of anterior sacral roots S2, S3, and S4 in patients with spinal injury. S2 stimulation provoked isolated low-pressure colorectal contractions. S3 stimulation initiated frequency-dependent high pressure colorectal motor activity which appeared peristaltic and was enhanced with repetitive stimuli. S4 stimulation increased colonic and rectal tone. Quantitative responses were maximal at the splenic flexure and rectum. Pelvic floor activity was stimulated in increasing magnitude from S2 to S4. These results of distal bowel motility were achieved by an implanted Brindley stimulator. A newer generation of externally active stimulators are envisaged for the control of lower bowel in fecal incontinence. Women with intractable constipation following hysterectomy had significantly increased rectal volume and compliance together with deficits of rectal sensory function. Following stimulation with Prostigmine (neostigmine) a colorectal motility gradient was paradoxically reversed in the patients following hysterectomy, thus constituting a functional obstruction. Denervation supersensitivity was demonstrable in 2 patients tested with carbachol provocation. These findings suggest dysfunction in the autonomic innervation of the hindgut in some patients following hysterectomy. PMID- 1462614 TI - Fecal incontinence: indications for repairing the anal sphincter. AB - Incontinent patients should be comprehensively investigated by objective tests, especially manometry, continence tests, and electromyography. Manometry can be used to predict the functional outcome and to calibrate the sphincter repair. Pure anatomical defects of the anal and pelvic musculature deserve surgical correction with or without overlapping the muscle ends. If the repair is delayed it should be done after a 3 month interval. A protective colostomy has to be performed in complex cases and in cases with septic complications. Before closing the colostomy, the ano-rectal function should be assessed. Acceptable continence can be restored in the majority of the patients, the outcome depending on the extent of local defects and the severity of concomitant pelvic floor neuropathy. Skeletal muscle transposition remains an esoteric approach to be used only in selected patients; the implantation of a neuromuscular stimulator seems to be warranted. In the presence of important functional deficits, sphincter repair may create a situation where additional conservative measures become more effective. A post-anal repair may be considered 3-12 months after rectopexy or sphincter repair. Incontinence based on pure functional defects is initially treated conservatively. A post-anal repair may improve the situation in two thirds of the patients but fails to help those who need it most. Failure seems to be related to a continuing neuropathic process. A peri-anal prosthetic band implant may be a valuable alternative in such patients. A sigmoidostomy is a measure of last resort. The prevention of fecal incontinence is most important and concerns surgeons, obstetricians, and physicians. PMID- 1462616 TI - Anismus: the cause of constipation? Results of investigation and treatment. AB - Anismus, or failure of the somatic sphincter apparatus to relax at defecation, has been implicated as a major contributor to the problem of obstructed defecation. Current diagnostic methods depend on laboratory measurements of attempted defecation and the most complex, dynamic proctography has been the mainstay of diagnosis. Using a new computerized ambulatory method of recording sphincter function in these patients at home, we report an 80% reduction in our diagnostic rate suggesting that conventional tests fail to accurately diagnose this condition, probably because they poorly represent the natural physiology of defecation. Treatment of this distressing condition is more complex and a variety of surgical and pharmacological measures have failed. Biofeedback retraining of anorectal function of these patients has been very successful and represents the management of choice. PMID- 1462615 TI - Treatment of complete rectal prolapse: to narrow, to wrap, to suspend, to fix, to encircle, to plicate or to resect? AB - Selection of the best surgical procedure for the treatment of complete rectal prolapse is difficult amid the many different techniques for which excellent results are reported. A critical review is given. It is concluded that any surgical procedure with rectal mobilization and fixation as a standard maneuver will lead to a recurrence rate of 2% to 4%. Advocacy of additional maneuvers to make the procedure easier is acceptable if it does not lead to a higher complication rate. But to obtain a better result its benefit has to be proven, either by a large prospective double-blind study, or by tests from the colorectal laboratory. New surgical techniques for rectal prolapse should therefore be based, not only on a low recurrence and complication rate, but also on tests that evaluate the effect of the procedure on fecal continence. PMID- 1462617 TI - Solitary rectal ulcer: the place of biofeedback and surgery in the treatment of the syndrome. AB - Thirty-one patients with the solitary rectal ulcer syndrome were studied, the majority of whom presented with fresh blood per rectum and a rectal ulcer, mucorrhoea, or a varying degree of rectal prolapse. Fourteen patients were treated conservatively or with surgery and had a high rate of recurrence of the solitary rectal ulcer syndrome. Seventeen patients were treated with biofeedback for the associated obstructed defecation (anismus) either before or immediately after surgery with a lower recurrence rate. The final symptomatic cure rate was similar in both groups but 15 episodes of recurrence requiring further surgery were encountered in the non-biofeedback group compared to 4 recurrences in the biofeedback group. PMID- 1462618 TI - New diagnostic imaging in rectal cancer: endosonography and immunoscintigraphy. AB - Endosonography of the rectum, combining the advantages of both endoscopy and sonography, provides information not at present available from other imaging modalities. It is remarkably accurate in the pre-operative assessment of tumor penetration. In the evaluation of lymph nodes, the specificity and sensitivity is 83% and 72%, respectively. For the detection of local recurrence in asymptomatic patients promising results can be obtained. In contrast, the potential benefits of immunoscintigraphy in patients with rectal cancer have yet to be determined but preliminary results indicate that immunoscintigraphy in combination with endosonography may assist the surgeon in confirming or excluding the suspicion of recurrence. PMID- 1462619 TI - Results of radical surgery for rectal cancer. AB - This paper examines the hypothesis that a reduction in the distal mural margin during anterior resection for sphincter conservation in rectal cancer excision is safe, provided total mesorectal excision is undertaken with wash-out of the clamped rectum. One hundred ninety-two patients underwent anterior resection and 21 (less than 10%) patients underwent abdomino-perineal excision (APE) by one surgeon (RJH). Anterior resections were classified as "curative" (79%) and "non curative" (21%); in the "curative" sub-group less than 4% of patients developed local recurrence. The series was retrospectively analyzed for the effect of mural margins on local recurrence with 152 patients undergoing "curative" anterior resections and 40 patients undergoing "non-curative" resections. In the 152 specimens from curative resections, 110 had a resection margin greater than 1 cm and 42 had a resection margin less than 1 cm. Four patients developed local recurrence in the greater than 1 cm margin group (95% confidence interval: 0.8% 7.8%) and no patients developed local recurrence in the less than or equal to 1 cm margin group (95% confidence interval: 0%-5.9%). In each patient with local recurrence a cause for failure was apparent. There was no statistically significant difference in local recurrence rate between the less than or equal to 1 cm margin group and the greater than 1 cm margin group. A reduction in resection margin therefore did not compromise survival after anterior resection. The significance of lateral resection margins is discussed. The role of deep radiotherapy and cytotoxics are considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462620 TI - Pre-operative and post-operative radiotherapy and rectal cancer. AB - The appropriate role for additional radiotherapy in patients with resectable rectal cancer is not yet settled. Irradiation has been considered by surgeons and radiotherapists as superfluous since no effect on survival has been shown. However, numerous trials have demonstrated that peri-operative radiotherapy decreases an often high local recurrence rate while others believe it has a definite place in routine management. Several surgeons have, on the contrary, claimed that a skilled surgeon compared to a less skilled surgeon, will get the same acceptably low local recurrence rates. Since we will probably never have a randomized trial comparing "good" and "bad" surgeons, this argument cannot be settled. A further obstacle arises in the difficulty of persuading surgeons to organize their routine work so that it is performed in an optimal way by those specializing in this field. The question also arises whether radiotherapy should be delivered pre-operatively, postoperatively or as a "sandwich" technique, i.e., both pre-operatively and postoperatively. According to radio-biological considerations and results from reported trials, the best effect on local tumor control has been achieved using pre-operative radiotherapy. PMID- 1462621 TI - Results of the double stapling procedure in pelvic surgery. AB - The double stapling technique for rectal reconstruction after resection involves closing the lower rectal segment with a linear stapler and performing the anastomosis using a circular stapler across the linear staple row. The purpose of this report is to review the results of double stapling, present our experience, and draw conclusions from the material available. We have utilized the double stapling technique in 80 patients for primary anastomoses and in 11 patients for secondary anastomoses following Hartmann procedures. Twenty-one anastomoses were at or near the dentate line. Fifty-six patients had rectal carcinoma, 29 patients had diverticulitis, 3 patients had carcinoma of the ovary, and 1 patient each had traumatic rectal perforation, volvulus, or rectal prolapse. Complications in the total 91 patients included 3 anastomotic leaks (3.3%), 1 postoperative hemoperitoneum (1.1%), and 3 strictures (3.3%). No anastomosis was protected by diverting colostomy. There were no operative deaths. Of 43 patients with cancer available for follow-up, 4 patients have developed local recurrence. The technique has been modified for ileoanal anastomosis during abdominal restorative proctocolectomy for ulcerative colitis and familial polyposis and early results are favorable. The double stapling technique provides a safe method for rectal reconstruction at or near the dentate line and offers the following advantages over other stapler techniques: (1) It eliminates the frustrating distal pursestring; (2) The rectal segment is not opened, minimizing contamination; and (3) It avoids gathering the sometimes generous circumference of the rectum on a pursestring thus allowing a more precise distal donut. PMID- 1462622 TI - The results of pouch surgery after ileo-anal anastomosis for inflammatory bowel disease: the manometric assessment of pouch continence and its reservoir function. AB - Anal sphincter function after restorative proctocolectomy has mainly been investigated by anal manometry. A significant decrease of basal pressure up to 45%, has been recorded postoperatively, possibly due to sphincter stretch during endoanal mucosectomy. Both abdominal mucosectomy and anastomosis at the level of the anorectal ring have been reported to prevent anal sphincter damage and lead to better continence. The striated sphincter is not significantly affected by the surgical procedure. Pouch-anal inhibitory reflex is partly maintained in the presence of a rectal cuff which leaves the ganglionic plexus unaltered; a satisfactory continence is also retained in the absence of the reflex when the rectum is totally excised. Pouch capacity, compliance and motility have been investigated by endoluminal balloon and probes. Pouch emptying has been studied by a "porridge" test, by a semi-solid medium labelled with technetium-99, and by other methods. A more effective storage function is achieved by large capacity reservoirs which lower the bowel frequency. The motor response to pouch distension, to a meal, and to pharmacological stimuli is usually counteracted by sphincter contraction. Ileal hypermotility may lead to fecal leakage mainly in the presence of weak sphincters. Poor pouch emptying may be related to an anal stricture. PMID- 1462624 TI - Recent progress in surgery for the victims of disaster, terrorism, and war- Introduction. PMID- 1462623 TI - Results of pouch surgery after ileo-anal anastomosis: the implications of pouchitis. AB - The ileal pouch-anal operation is the procedure of choice for those suitable patients requiring surgery for chronic ulcerative colitis or familial adenomatous polyposis. The functional results are generally good but pouchitis remains a significant and poorly understood complication. This review encompasses factors relating to pouchitis, e.g., bacteriological, functional and histological changes, with emphasis on its biology and treatment, and the long-term implications. PMID- 1462625 TI - The medical effects of conventional weapons. AB - The medical effects of weapons used in modern conventional warfare are, overwhelmingly, penetrating. Fragments from explosive munitions such as shells, rockets, and grenades are the predominate source of missiles, especially in high intensity war. Bullets from assault rifles and machine guns cause fewer casualties, except in counterinsurgency operations. The threat from penetrating missiles depends upon the part of the body that is struck and, to a lesser extent, upon the physical characteristics of the missile. The missile's mass and velocity determine its potential to do physical damage, but the extent to which this potential is realized depends upon diverse factors such as shape, construction, and stability. The American experience in the wars of this century indicate that approximately 20%-25% of all casualties died on the battlefield and are therefore classified as killed in action. Approximately 3%-5% die while receiving care, and thus are classified as died of wounds. Wounds of the brain or heart and great vessels are the most common causes of death. Prevention of sepsis in soft-tissue and orthopedic wounds is the major medical treatment problem in survivors. Since it determines the quality and quantity of combat casualty care, the single most important factor determining mortality or morbidity for combat casualties is the tactical situation. PMID- 1462626 TI - The relationship of blast loading to death and injury from explosion. AB - Death and injury from explosion are becoming ever more frequent. In this study an attempt is made to relate the blast loading suffered by individual victims of explosions to the injuries sustained. It includes 828 servicemen killed or injured by explosions in Northern Ireland. Two hundred sixteen servicemen were killed, most of them before any assistance could be rendered. In those exposed to a higher blast loading, blast lung was common. Those exposed to lower blast loading died primarily of head injuries. Body armour was worn by 90% of the servicemen and probably reduced the number of fatal secondary missile injuries. PMID- 1462627 TI - Crush injury and crush syndrome. AB - Crush injury is caused by continuous prolonged pressure on the limbs. It is found in patients extricated after being trapped for at least 4 hours. The main injury is to the muscles of the limbs. Treatment should be conservative and fasciotomy should be avoided. If fasciotomy is performed, it should be followed by radical debridement of the injured muscle in an attempt to avoid infection of the injured limb. Infection endangers the patient's life and is the main cause of morbidity and mortality today. The outcome of conservative local treatment of crush injury is much superior to that of operative treatment. The pathophysiology of crush injury is not fully understood and no good animal model is known. Crush syndrome, which is the general manifestation of crush injury, is better understood. If not prevented, it will lead to acute renal failure. A method for preventing acute renal failure is discussed and a protocol is described. There is no doubt that prevention of acute renal failure is the goal in the treatment of crush syndrome and can be achieved. PMID- 1462628 TI - Triage: in austere environments and echeloned medical systems. AB - Although triage as a medical sorting process was originally developed and applied to echeloned military field medical systems dealing with mass casualties, the term has now permeated most aspects of medical practice. This essay attempts to refocus on triage in military and disaster settings, emphasizing the relationship of the echeloned system organization to the triage process, and the various non medical factors which may influence triage decisions and priorities. Due to the lack of any analogous civilian experience, it is essential that all health personnel who may be involved in an echeloned care system gain and maintain proficiency by frequent involvement in appropriate training exercises, the characteristics of which are described. PMID- 1462629 TI - The Red Cross classification of war wounds: the E.X.C.F.V.M. scoring system. AB - The Red Cross classification of war wounds is based upon features of the wound, not upon weaponry. It is proposed as a new means of understanding, communicating, and gathering information about war wounds and their management. The wound score is based on the skin wounds and the presence of a cavity, fracture, vital injury, or metallic bodies in the wound. All wounds so scored can be graded according to severity and typed according to structures injured; consequently, wounds are identified by their clinical significance. A study of 247 wounds shows the feasibility of scoring wounds in the field and yields surgically relevant information about bullet and fragment wounds. The applications of the classification are to wound assessment, establishing a scientific basis to war surgery, surgical audit, and collecting wound data from the field. PMID- 1462630 TI - Irradiated trauma victims: the impact of ionizing radiation on surgical considerations following a nuclear mishap. AB - The combination of conventional traumatic injuries and radiation exposure has synergistic consequences, the full extent of which may take days to weeks to become apparent. Our understanding of such is derived from a variety of laboratory and clinical scenarios involving both therapeutic and accidental exposures. When presented with such an individual one must discern whether the victim has been bodily contaminated versus exposed to a source or both. The former will necessitate decontamination procedures which may be as simple as declothing and showering the individual. Simply removing the victim from the source will suffice to halt further radiation induced injury. In the vast majority of cases basic life support and other emergency medical procedures should be expeditiously instituted as warranted and without fear of personal hazard for health care teams. Following stabilization, further medical/surgical support must be predicated upon the extent of the radiation injury with the circulating absolute lymphocyte count serving as both a reliable and readily accessible indicator of the degree of underlying radiation injury. As radiation has profound consequences on immune and wound healing systems, therapies must be tempered by an understanding of the impact of radiation upon these systems. Overall, the consequences of irradiation injury will be the potential for an exacerbation of the effects of conventional traumatic injuries with a higher than expected morbidity and mortality. PMID- 1462631 TI - Blunt and penetrating chest injuries. AB - The management of chest injuries begins with knowledge of what happened to the patient at the time of the traumatic incident and converting this information into possible diagnoses. The various organs of the chest cavity are discussed emphasizing the controversies that attend the management or diagnosis of each one. PMID- 1462632 TI - Advances in treatment of vascular injuries from blunt and penetrating limb trauma. AB - Military and civilian experience has contributed to the current state of the art in management of extremity vascular injuries. Thorough physical examination and judicious use of emergency center arteriography and formal arteriography provide means for prompt diagnosis and treatment which is critical is limb loss and disability are to be avoided. Prosthetic graft material has provided an alternative to vein grafting in many circumstances for arterial and venous injuries. Compartment syndrome should be anticipated when an ischemic extremity is revascularized and fasciotomy should be used liberally. Vascular repairs are the first priority in extremity wounds, but associated injuries to bones, joints, soft tissues, and nerves are often critical determinants of rehabilitation once blood supply has been re-established. The best results are obtained when a multidisciplinary approach is used combining expertise in orthopedic surgery, neurosurgery, and plastic surgery. PMID- 1462633 TI - Vascular trauma: a brief military perspective. PMID- 1462634 TI - Abdominal trauma in war. AB - In war, the percentage of casualties with abdominal wounds on battlefields is near 20%. Roughly half of these casualties die almost immediately from bleeding. Wounding agents are most often either bullets or fragments from various detonating devices. Severity of pathology induced by these agents and prolonged lag time between injury and treatment constitute major differences between peace and war abdominal injuries. Since the means of diagnosis is unsophisticated in war, penetrating abdominal injury leads to systematic exploratory laparotomy, although 10% to 20% of explorations are negative. The management of colon lesions remains a controversial issue. In modern war surgery manuals, primary colon repair is not totally condemned and is generally considered acceptable, but under stricter criteria than in civilian practice. In abdominal war wounds, mortality rate dropped from 53% during World War I to 18-36% at the end of World War II. In Vietnam it went down near 10% in some limited hospital series. But other data collected during that conflict show a less rosy picture. Of 476 abdominal casualties, the total mortality reached 42%. The hospital mortality among the survivors was 11.5%. Death in cases where abdominal wound was the primary lesion was due to hemorrhage in 60%, sepsis in 25%, and pulmonary insufficiency in 15%. Survivors had an average of 1.8 injured organs. PMID- 1462635 TI - A new technique for the resection of gastric cancer: modified Appleby procedure with reconstruction of hepatic artery. AB - The Appleby operation allows resection of gastric cancer with lymph nodes around the stomach and celiac axis en bloc. Hepatic arterial blood flow after resection of the celiac axis is supplied by the superior mesenteric artery. In some patients, however, hepatic arterial flow becomes decreased after resection of the celiac axis. This abrupt reduction of hepatic arterial blood flow sometimes causes postoperative complications such as severe liver dysfunction or gallbladder necrosis. To prevent the reduction of hepatic arterial blood flow and to perform the Appleby operation more safely, we modified the Appleby operation to include reconstruction of the hepatic artery. We found that after dissection of lymph nodes around the hepatoduodenal ligament, the proper hepatic artery and gastroduodenal artery can be well mobilized and it becomes possible to anastomose the celiac axis to the common hepatic artery directly without using anticoagulants. From May, 1989 to November, 1990, 15 patients with advanced gastric cancer underwent the modified Appleby procedure at Kinan General Hospital. Postoperatively, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were determined for evaluation of liver function. These levels were almost the same as those found after traditional total gastrectomy without resection of the celiac axis. Indocyanine green (ICG) clearance tests were performed before and 1 month after operation. There was no significant difference between the preoperative and postoperative values. Common hepatic arterial flow after celiacohepatic anastomosis was 390 ml/min on average. The modified Appleby procedure can be done quite safely. PMID- 1462636 TI - Optimal timing of elective indirect inguinal hernia repair in healthy children: clinical considerations for improved outcome. AB - Experience with several incarcerations that resulted in emergent surgery for children with known indirect inguinal hernias prompted this review to determine if there is an optimal time after hernia diagnosis during which elective repair should be undertaken to avoid incarceration. Over a 30 month period, 228 children less than 10 years of age underwent 303 indirect inguinal hernia repairs. They were analyzed for age, sex, interval between diagnosis and repair, predisposing conditions, major complications, and length of hospitalization. Excluded were 21 children who presented with incarceration of a previously undiagnosed indirect inguinal hernia that required operative reduction, 13 children with conditions predisposing to indirect inguinal hernia, and 53 children for whom the interval between diagnosis and repair was unknown, leaving a study group of 141 children who underwent 190 indirect inguinal hernia repairs. Nearly 13% (18 of 141) of the children developed incarcerated hernia prior to elective repair. Compared to children who underwent repair of a reducible indirect inguinal hernia, those with incarceration were more likely (p less than 0.05): 1) to have major complications (11% vs 0.6%), 2) to have a shorter interval between diagnosis and repair (26 vs 49 days), 3) to be younger (7.5 vs 25.6 mos), and 4) to require greater than 24 hours of hospitalization. Had children with reducible incarcerated indirect inguinal hernia been hospitalized and undergone repair 24 to 48 hours later, 83% of subsequent incarcerations would have been prevented. Furthermore, this experience supports the recommendation that for healthy children less than 10 years of age, indirect inguinal hernia repair should be performed on a semi elective basis within 7 days of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462637 TI - Treatment of cystic lesions of the thyroid by ethanol instillation. AB - We analyzed the results of ethanol sclerotherapy in 61 patients with cystic thyroid lesions which recurred after aspiration. Cytologic study showed all of the lesions to be benign. The patients were followed clinically and ultrasonically 1 month and 6 or more months after treatment. If the cystic lesions recurred, repeated treatment was offered. During the follow-up, 36 (59.0%) patients experienced no recurrence after the initial treatment and 5 (8.2%) patients received treatments 2 or more additional times. In 44 (72.1%) of the 61 patients, the cystic lesion almost disappeared or decreased in size, but in 17 (27.9%) patients it did not decrease. Four patients underwent surgery after the ethanol sclerotherapy. Although no severe complications were observed, there were complaints of slight pain in 12 patients, severe pain in 1 patient, and a drunken feeling in 1 patient. We consider instillation of ethanol into recurrent cystic lesions of the thyroid to be a simple, safe, economical, and effective treatment. PMID- 1462638 TI - Multifactorial analysis of septic bile and septic complications in biliary surgery. AB - A unifactorial analysis for possible risk factors was applied to 2,700 consecutive operations for benign disease of the biliary tract. A series of high risk factors in relation to positive bacteriology and septic complication could be identified. These risk factors were patients who were elderly (greater than 70 years; p less than 0.001), those who were diabetic, those who had a serum bilirubin greater than 1.1 mg% (p less than 0.001), those who had acute cholecystitis (p less than 0.001), and those in whom choledochal stones were found (p less than 0.001). Using a multivariate analysis, we concluded that in patients with no risk factors (56.9%) the incidence of a positive bacteriology was low (10.9%) and they should receive no antibiotic prophylaxis. Patients with one risk factor (24%), had a 36% incidence of positive bacteriology and minimal pre-operative prophylaxis is recommended. Patients with two or more risk factors (19.1%) had a 77.6% incidence of positive bacteriology and full peri-operative prophylaxis is recommended, starting pre-operatively and continuing for 3 to 5 days postoperatively. The aim of this study was to identify patients at risk for septic complication in biliary surgery and to create new guidelines for the antibiotic treatment of selected groups. PMID- 1462639 TI - Comparison of topical hemostatic agents in elective hepatic resection: a clinical prospective randomized trial. AB - To compare the difference in efficacy of microcrystalline collagen powder (CL) and fibrin glue (FG) in elective hepatic resection, 62 patients (female 14, male 48) with ages ranging from 51 to 75 years were randomly allocated to receive either CL or FG as a topical agent during hepatectomy. There were no significant differences between the patients treated with CL (n = 31) and those treated with FG (n = 31) regarding sex, age, liver function, coagulation function, platelet counts, type of liver resection, and operative duration. A dry cut surface of the liver was obtained during surgery in 27 (87%) patients and 25 (81%) patients treated with CL and FG, respectively. Both CL and FG showed similar hemostatic effects. The CL and FG groups were not different in terms of postoperative rebleeding, bile leakage, or morbidity and mortality rates (6% vs. 6%, 6% vs. 6%, 45% vs. 39%, and 13% vs. 10%, respectively). Of the 52 patients with a dry cut surface of the liver during surgery, 3 patients in the CL group encountered rebleeding (n = 1) or bile leakage (n = 2) from the cut surface postoperatively, while no such complications were noted in the FG group. The results seem to favor FG for reliability in the postoperative period. The application of CL or FG may be better performed with consideration of the characteristics of each agent. PMID- 1462640 TI - Endoscopic subfascial sectioning of incompetent perforating veins in treatment of primary varicosis. AB - Subfascial elimination of incompetent perforating veins is the most effective therapeutic principle in the treatment of trophic skin disorders associated with varicosis. A recently developed endoscopic technique allows accurate sectioning of perforating veins with direct observation of the veins and minor trauma. From November 1986 to July 1991 endoscopic sectioning of perforating veins was performed in 72 patients (103 legs). The most frequently transected perforating veins were Cockett's veins (n = 219), 24 cm perforating veins (n = 83), and Boyd's perforating veins (n = 82). Postoperative delayed wound healing was observed in 3 (2.9%) legs with pronounced trophic skin disorders in the lower extremities. Two patients complained of dysesthesia in the area of distribution of the sural nerve. Further complications recorded were extended subcutaneous hematoma in 6 (5.8%) legs and postoperative dysesthesia in the area of distribution of the saphenous nerve in 10 (9.7%) legs. At follow-up examination (mean 27 months postoperatively) clinical investigation and Doppler sonography showed newly formed incompetent perforating veins in only 2 lower legs. Radiography at follow-up revealed one incompetent Dodd's perforating vein in 1 leg, which was the starting point of pronounced recurrent varicosis in the lower leg. After an average follow-up of greater than 2 years, we recorded the occurrence of new varices in 9 lower legs. Staging of chronic venous incompetence showed an upward trend ranging from change to a more favorable stage to complete cure. Findings were unchanged in only 10% of the patients. There was no case of postoperative aggravation. PMID- 1462641 TI - Biliary ascariasis: surgical aspects. AB - Presentation and management of 204 patients with biliary ascariasis seen over a period of 5 years is reported from a highly endemic area of Kashmir. Ultrasonography is the single most useful means of diagnosis. Endoscopic retrograde cholangiopancreatography is extremely helpful. Most patients respond to conservative management and around one-fifth of all patients require surgery. PMID- 1462643 TI - Whither medicine? PMID- 1462642 TI - 24-hour intragastric pH measurement in the assessment of duodenogastric reflux. AB - In this study we compared the results of measurement of duodenogastric reflux using 24-hour intragastric pH monitoring and nasogastric aspiration with analysis of bile acid and alpha amylase concentrations. Eight patients were studied at least 5 months after biliary and/or gastric surgery. The correlation coefficient of pH and bile acid concentration was 0.36 (p less than 0.001) and of pH and amylase concentration was 0.48 (p less than 0.001). If a pH greater than 4.0 was taken to indicate duodenogastric reflux this had a sensitivity of 84% compared with either high bile acid or amylase concentration. Bile acid concentration has been the "standard" method of measuring duodenogastric reflux. pH monitoring is relatively simple to perform, causes little patient distress, and can measure episodes of duodenogastric reflux over a continuous 24-hour period. PMID- 1462644 TI - Two objections to Adams' opinion. PMID- 1462645 TI - Adams offered us excellent advice. PMID- 1462646 TI - Surgical procedures in centenarians. AB - Sixteen patients 100 years of age and older underwent surgical procedures at a single institution during the 11-year period ending December 1991. There were 11 (69%) females and five males. Patient ages ranged from 100 to 104 (mean, 101.1 years). Procedures included six ophthalmologic operations, three permanent pacemaker implantations, three compression hip screw fixations, two leg amputations, one hemiglossectomy, and one cystostomy. There was one (6%) perioperative death. Long-term follow-up was established for each patient. One year survival rate in these 16 centenarians was 69%. We conclude that selected patients 100 years old and older can survive certain surgical procedures with acceptable perioperative and long-term results. PMID- 1462647 TI - Neuroleptic malignant syndrome in a patient with neurosyphilis. AB - Neuroleptic malignant syndrome (NMS) is a catatonic-like syndrome of uncertain etiology occurring in patients taking dopamine blocking medications. The paper describes how NMS presents and is treated and reports the case of a patient with undetected neurosyphilis who developed NMS. The case highlights the need for a thorough organic evaluation of all patients with initial-onset psychotic features and suggests the possibility of a CNS cofactor--neurosyphilis--initiating the NMS as proposed by other researchers. PMID- 1462648 TI - Levels of physician responsibility in diagnosis and treatment of addiction. PMID- 1462649 TI - Increasing incidence of prostate cancer in Wisconsin, 1980-1990. PMID- 1462650 TI - Mobile clinic brings care to Ukraine. PMID- 1462651 TI - From municipal hospital to medical center: Milwaukee County General Hospital, 1965-1980. PMID- 1462652 TI - Evaluating measures to control intestinal parasitic infections. AB - Intestinal parasitic infections are among the most common infections of humans in developing countries, but the resources available for their control are severely limited. Careful evaluation of control measures is essential to ensure that they are cost-effective. The evaluation of the effects of control on intestinal helminths and intestinal protozoa requires an understanding of the different epidemiological patterns of these two groups of parasites. The transmission dynamics and morbidity associated with the major helminth infections (Ascaris lumbricoides, Trichuris trichiura and the hookworms) are dependent on the size of the worm burdens. Thus the important parameter for evaluating the impact of control on morbidity and transmission is the intensity of infection, which can be assessed by determining the mean density of parasite eggs in faecal specimens. Estimation of intensity is subject to systematic errors, however, due to the complex pattern of worm burden distributions. The frequency distribution of burdens is highly overdispersed, and individuals exhibit predisposition to particular levels of infection. Furthermore, mean intensity is age-dependent, in a species-specific manner, and is clustered spatially and within families. These complex patterns imply that the estimation of intensity is exceptionally sensitive to the size and demographic structure of the population sample selected for assessment. They also have the effect that prevalence estimates, the most commonly used measures of infection in communities, can seriously mislead. Paradoxically, prevalence is least useful where infection is most common because the relationship between prevalence and intensity is most markedly non-linear when the prevalence is high. Thus in areas where control is most needed, evaluation using prevalence might suggest that control had failed while evaluation by intensity would, correctly, show the measure of success. With the major protozoan infections (Entamoeba histolytica, Giardia duodenalis and Cryptosporidium parvum) an estimate of intensity is of little value and the central parameter for evaluation is prevalence. Prevalence does exhibit age and spatial heterogeneity, which may be species-specific, so there remains a need to ensure a consistent sample structure, although this is less critical than for the helminths. The major constraint on evaluating the control of protozoan infections is the need to identify pathogenic species and, in some cases, pathogenic strains. Harmless commensal protozoans are ubiquitous and often morphologically very similar to pathogens, but their control is both unnecessary and impracticable. Species such a E. histolytica appear to exist as strains with differing pathogenicity, thus control will be cost-effective only if the focus is on pathogenic strains. Effective diagnosis is therefore central to the evaluation of the control of protozoan infections.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1462654 TI - Waterborne disease outbreaks in the United States of America: causes and prevention. AB - National statistics on waterborne outbreaks in the United States of America show that 1,702 waterborne outbreaks with 542,018 cases of illness and 1,089 deaths have been reported. Almost all deaths prior to 1940 were due to typhoid fever; 9 deaths from other causes have occurred since 1971. During the past decade, 291 waterborne outbreaks were reported in community (43%) and noncommunity (33%) systems, and from the ingestion of contaminated water from recreational (14%) and individual (10%) water sources. Although several large waterborne outbreaks occurred during the past decade, most were in small communities. The number of illnesses per outbreak in noncommunity systems during the past decade is much larger than that reported during any previous period, and the magnitude of these outbreaks indicates the potential effect on the travelling, transient population. During 1981-1990, contaminated, untreated groundwater or inadequately disinfected groundwater was responsible for 43% of all reported waterborne outbreaks, and contaminated, untreated surface water or inadequately treated surface water was responsible for 24% of all reported outbreaks. The use of untreated groundwater has declined in importance as a cause of outbreaks, and more outbreaks are now caused by inadequate or interrupted disinfection of groundwater. The increased occurrence of outbreaks in disinfected groundwater systems may be due to (i) increased use of disinfection with little effort to reduce or eliminate sources of contamination, and (ii) not providing effective, continuous disinfection. In surface-water systems, outbreaks occur primarily because of inadequate or interrupted disinfection in systems that do not provide filtration, but a large increase in outbreaks has recently occurred in filtered systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462653 TI - The magnitude of mortality from acute respiratory infections in children under 5 years in developing countries. AB - This article reviews the available evidence of mortality from acute respiratory infections (ARI) among children aged under 5 years in contemporary developing countries and compares the findings with European populations before 1965. In European populations before 1965, the level of mortality was found to be a determinant of the proportion of deaths due to ARI. There were marked differences according to regional patterns of mortality. Deaths from ARI played a smaller role after 1950, when the use of antibiotics became generalized. In developing countries, the role of ARI mortality seems to be similar to the European experience. The age pattern is very marked. In absolute values, ARI mortality is highest in the neonatal period and decreases with age. In relative values, ARI mortality is highest in the postneonatal period. ARI, mainly pneumonia, accounts for about 18% of underlying causes of death in developing countries. Pneumonia and other ARI are frequent complications of measles and pertussis; ARI is also commonly found after other infections and in association with severe malnutrition. Virtually no data are available in developing countries to provide final estimates of the role of ARI in mortality of children aged under 5 years. However, the WHO figure of 1 out of 3 deaths due to--or associated with--ARI may be close to the real range of the ARI-proportional mortality in children of developing countries. Results are discussed in light of the definitions of ARI used in various studies, the difficulties in ascertaining and coding multiple causes of death and the quality of data from some sources. PMID- 1462655 TI - Surveillance and control of emerging zoonoses. AB - "Emerging zoonoses" are defined as zoonotic diseases caused either by apparently new agents, or by previously known microorganisms, appearing in places or in species in which the disease was previously unknown. New animal diseases with an unknown host spectrum are also included in this definition. Natural animal reservoirs represent a more frequent source of new agents of human disease than the sudden appearance of a completely new agent. Factors explaining the emergence of a zoonotic or potentially zoonotic disease are usually complex, involving mechanisms at the molecular level, such as genetic drift and shift, and modification of the immunological status of individuals and populations. Social and ecological conditions influencing population growth and movement, food habits, the environment and many other factors may play a more important role than changes at the molecular level. Diseases associated with changing farming practices, trade and consumer habits. Bacterial enteric diseases due to Salmonella enteritidis and Echerichia coli 0:157 are examples of diseases associated with changing farming practices and consumer habits. The increasing trade in live animals for animal production and research led to the introduction of the New World screwworm to the Libyan Arab Jamahiriya in 1989 and an Ebola like virus in monkeys in quarantine facilities in the United States of America. The development of the epidemics of bovine spongiform encephalopathy (BSE) in the United Kingdom is due to multiple factors including the increasing use of ruminant proteins as feed for animals. Diseases associated with changing environmental conditions which influence reservoirs, vectors and/or victim species population parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462656 TI - [Cholera, 1991--old enemy, new face]. AB - The cholera epidemics of the XIXth century are described and reviewed. The extent, incidence and case-fatality rate for the disease in the seventh pandemic are described. The global epidemiological situation and its trend at the end of 1991 are analysed. A review of cholera epidemiology highlights the factors that might explain the less tragic nature of the disease today. The role of water, food and direct contagion in transmission of cholera over the last 20 years is considered in the light of recent studies and with special reference to the epidemic in Latin America, where the intense emotion aroused by the disease has prompted vigorous action that could produce significant and lasting progress in the health field. PMID- 1462657 TI - The global epidemiology of the HIV/AIDS pandemic and its projected demographic impact in Africa. AB - The global epidemiology of HIV/AIDS has evolved to the point that the pandemic now predominantly affects heterosexuals, especially in developing countries. This article summarizes the status of the HIV/AIDS pandemic as of the early 1990s; provides estimates and short-term projections of AIDS mortality in a hypothetical country of sub-Saharan Africa; projects the potential demographic impact of AIDS in a hypothetical sub-Saharan country; and describes the major problems associated with modelling the long-term demographic impact of this pandemic. Estimated AIDS cases and deaths up to 1992 were extrapolated from public health surveillance data and through use of the WHO model. Estimates of HIV seroprevalence were based on available HIV serological data. For developed countries, HIV estimates developed by national experts and/or national AIDS programmes were used, and for developing countries estimates by regional experts were used or were prepared by WHO. For the first half of the 1990s, projections of AIDS cases and deaths were derived from the WHO model; beyond the mid-1990s, the potential effects of AIDS on selected demographic indicators were derived from a demographic projection model developed by the World Bank. Although estimates and long-term projections cannot be made with great precision, the general dimensions of the HIV/AIDS pandemic have been more clearly delineated now at the start of its second decade. Epidemiological data indicate that in industrialized countries, where extensive spread of HIV began in the late 1970s or early 1980s, the majority of HIV infections occurred during the first half of the 1980s.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462658 TI - Control of pertussis in the world. AB - Available data indicate that pertussis remains an important disease during infancy and childhood, particularly among those who are inadequately immunized. Over the past 15 years, successful immunization programmes have been implemented in most countries in the world. Some problems have arisen in the industrialized world where pertussis had been well controlled previously. The underlying causes of these problems are apathy and complacency on the part of physicians and parents, negative attitudes to immunization spread by anti-immunization pressure groups and litigation over liability for alleged vaccine-related injures. In developing countries, immunization coverage with primary series of three doses of DPT vaccine in infants exceeds 80%, but there are considerable differences in coverage rates between regions and between and within countries. Failures to reach and maintain high immunization coverage in developing countries are caused by multiple factors including weak management of immunization services, missing opportunities to immunize eligible children and ineffective information and motivation of mothers to return to complete the immunization series. To effectively control pertussis in the world, all countries should use available pertussis vaccines in immunization programmes for children. Since acellular pertussis vaccines are not generally available, the widespread use of DPT vaccine containing the whole-cell pertussis component should be continued. All efforts should be directed to increase or maintain high immunization coverage with DPT immunization at the level of at least 90% in all districts. Surveillance of pertussis morbidity should be strengthened in all countries and ideally, pertussis should be a reportable disease. More information on the present epidemiological pattern of pertussis, especially age distribution of pertussis cases in developing countries, is needed to develop the policy of booster doses of DPT vaccine in children > 1 year. PMID- 1462659 TI - Progress towards the global elimination of neonatal tetanus. AB - Neonatal tetanus (NT) can be effectively prevented through immunization and clean delivery practices. However, NT claimed the lives of over 433,000 infants in 1991. It is endemic in 90 countries throughout the world. Community-based neonatal tetanus mortality surveys helped to determine the true incidence of NT and revealed that, before immunization and clean delivery programmes were well established, approximately 1 million children contracted NT each year, of which 800,000 died. Mortality rates varied markedly by locale, ranging from 0 to 70 NT deaths per 1,000 live births. NT is still one of the most underreported notifiable diseases, and routine reporting systems identified only 4% of the NT cases estimated to have occurred in 1990. Based on WHO estimates, tetanus toxoid (TT) immunization and clean delivery practices prevented over 793,000 infant deaths in 1991. Of the 433,000 infants who died of NT that year, approximately 212,000 died in South-East Asia; 127,000 in Africa; 46,000 in the Western Pacific; 37,000 in the Eastern Mediterranean; and 1,300 in Europe. The Pan American Health Organization, using a separate methodology to estimate mortality, calculated that 10,500 newborns died of NT in the Region of the Americans. NT consistently clusters in geographical areas and population groups where shared practices or the environment enhance the risk of cord contamination. 80% of the newborns who died of NT in 1991 were born in South-East Asia or Africa. Of the 90 countries endemic for NT, 10% produce 80% of the world's NT deaths. NT also clusters at country level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462660 TI - Human leishmaniases: epidemiology and public health aspects. AB - The leishmaniases are parasitic diseases caused by different species of Leishmania, protozoa transmitted by sandflies, haematophagous biting insects. The reservoir hosts are man (anthroponotic cycle) and domestic or wild animals (zoonotic cycle). In man the disease takes four main clinical forms: visceral, cutaneous, mucocutaneous and diffuse cutaneous. Morbidity and mortality due to leishmaniasis are on the increase. Leishmaniasis, which is now found on four continents, is endemic in 82 countries (21 in the New World and 61 in the Old). The large number of endemic countries shows the global scale of the problem, though it is particularly severe in certain countries (90% of cases of visceral leishmaniasis come from 4 countries). Annual incidence is estimated at some 600,000 new clinical cases, officially reported, with a global prevalence of 12 million cases and a population at risk of approximately 350 million. It is very difficult to provide realistic estimates given the frequency of subclinical forms of visceral leishmaniasis, the large number of undiagnosed or unreported cases, the frequent absence of active screening and the fact that the leishmaniases are notifiable diseases only in a few countries (30 out of 82); nevertheless, it seems clear that official reporting of cases considerably underestimates the problem. Over the last two decades, it has become clear that leishmaniasis is a growing public health problem in terms of geographical extent and incidence with the occasional severe epidemic, such as that which occurred in Sudan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462661 TI - Chagas disease: epidemiology and prospects for interruption of transmission in the Americas. AB - American trypanosomiasis, or Chagas disease, is a parasitic disease caused by the haemoflagellate protozoa, Trypanosoma cruzi. The human infection occurs only in the Americas, where it is widely distributed in the periurban and rural areas of tropical and subtropical countries, from Mexico to Argentina and Chile. It is transmitted to man and other mammals mainly through insects, the triatomine bugs. As an enzootic disease, it extends from approximately latitude 42.5 degrees N (northern California and Maryland) to latitude 43.5 degrees S (southern Argentina and Chile). The results of several serological surveys indicate an overall prevalence of 16-18 million infected individuals. Up to 30% of those infected will develop the cardiac and/or hollow viscera irreversible lesions that characterize chronic Chagas disease. The endemic countries can be divided into four groups according to several indicators such as the number of confirmed human cases, the prevalence of seropositive tests in blood donors and population samples, the presence of infected vectors and reservoirs, and the existence or absence of coordinated actions towards the control of this disease. The domestic cycle of transmission, involving man and domestic animals such as dogs, cats, and domestic triatomine bugs, is the one that maintains the infections in the rural and periurban areas. Some triatomine species are well adapted to human dwellings where human and animal reservoirs are in intimate contact. The poor socioeconomic condition of the population and the domestic nature of the vector play crucial roles in maintaining the infection at an endemic level.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462662 TI - Progress towards the global eradication of poliomyelitis. AB - Poliomyelitis has been virtually eliminated from the industrialized countries by mass campaigns conducted with oral polio vaccine (OPV). In 1988, the World Health Assembly set the goal of global eradication of poliomyelitis by the year 2000. The current WHO strategy for eradication uses three primary activities beyond routine immunization with OPV. They are: (i) improved disease surveillance, (ii) building a global network of laboratories, and (iii) supplemental immunization strategies which include mass immunization campaigns with OPV at the national level, and targeted campaigns at the local level. Eradication of polio from the Region of the Americas is close and may have already been achieved. In other regions, the number of reported polio cases has declined, largely as a result of high immunization coverage. As more countries implement polio eradication strategies, the number of polio cases will continue to fall until eradication is achieved. PMID- 1462663 TI - The epidemiology of measles. AB - Measles is a highly infectious disease which has a major impact on child survival, particularly in developing countries. The importance of understanding the epidemiology of this disease is underlined by its ability to change rapidly in the face of increasing immunization coverage. Much is still to be learned about its epidemiology and the best strategies for administering measles vaccines. However, it is clear that tremendous progress can be made in preventing death and disease from measles with existing knowledge about the disease, and by using the presently available vaccines and applying well-tried methods of treating cases. Research in the coming decade may provide more effective vaccines for use in immunization programmes. An understanding of the basic epidemiology of measles is a prerequisite for effective control measures. PMID- 1462664 TI - The XXth century dengue pandemic: need for surveillance and research. AB - By the last decade of the XXth century Aedes aegypti and the 4 dengue viruses had spread to nearly all countries of the tropical world. Some 2 billion persons live in dengue-endemic areas with tens of millions infected annually. Dengue pandemics were also documented in the XVIIIth and XIXth centuries; they were contained by organized anti-Aedes aegypti campaigns and urban improvements. The XXth century dengue pandemic has brought with it the simultaneous circulation of multiple serotypes and in its aftermath, endemic dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). Nearly 3 million children have been hospitalized with this syndrome in the past 3 decades, mainly in South-East Asia. Recent outbreaks of DHF/DSS in the Pacific Islands, China, India, Sri Lanka, Cuba and Venezuela are indicators of the high intensity and rapid spread of dengue transmission. The magnitude of the XXth century dengue pandemic requires urgent improvements in early warning surveillance by WHO Member States and the development of the capacity to study underlying mechanisms of the disease. A key research question is why does DHF/DSS not occur with all second dengue infections? Two answers have been suggested: (1) a human resistance gene. Data from the 1981 DHF/DSS epidemic in Cuba have demonstrated the existence in blacks of a resistance gene. The effect of such a gene in reducing disease susceptibility of American and African blacks requires more study. (2) The existence of dengue "biotypes". Some, but not all biotypes may cause DHF/DSS during a second dengue infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462665 TI - Influenza--its impact and control. AB - Influenza is an underestimated public health problem. Epidemics spread rapidly from country to country and may affect as many as 500 million people across the world in a moderate influenza year. The disease, particularly influenza A, kills and the new influenza viruses which appeared in 1957 (Asian influenza) and 1968 (Hong Kong) are estimated to have caused at least 100,000 deaths in the United States of America. Deaths from influenza also occur in years when there is no new virus; at least 10,000 excess deaths have been documented in the United States during each of 18 different epidemics recorded from 1957 to 1985. Although most deaths are among the elderly, influenza occurs in all age groups with repercussions in schools and work places, and on hospital resources, at a high cost to society. As many as 79-80% of influenza cases can be prevented when the virus inducing the outbreak and the virus used in the influenza vaccine are closely related. Preventing 80% of cases would correspond in the United States to a saving of US $2.5 billion. People at the greatest risk of influenza-related complications are adults and children with chronic disorders of the pulmonary or cardiovascular systems, residents of nursing homes and of facilities for patients with chronic medical conditions. Other priority groups for vaccination are those at moderate risk of influenza-related complications such as healthy elderly persons, people with chronic metabolic diseases, children and teenagers on long term aspirin therapy. Groups potentially capable of transmitting influenza to high-risk persons should also be vaccinated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462666 TI - [Current aspects of acute gastrointestinal hemorrhage]. PMID- 1462667 TI - [Brain abscess as an endocranial complication of otologic diseases]. PMID- 1462668 TI - [Pleural carcinosis in renal cell cancer or pleural mesothelioma? A contribution to differential diagnosis]. PMID- 1462669 TI - [Temporary AV block III in correlation with borreliosis]. PMID- 1462670 TI - [Ventriculitis and peritonitis caused by Listeria monocytogenes--case report]. PMID- 1462671 TI - [A case from general practice (2): conspicuous laboratory findings]. PMID- 1462672 TI - [Friedrich Hoffmann (1660-1742)]. PMID- 1462673 TI - [Johannes Kentmann (1518-1574). On the 475th birthday of the physician and investigator of nature]. PMID- 1462674 TI - [Physician-patient interaction and university medicine]. PMID- 1462675 TI - [Hemodynamic effects of anti-arrhythmia substances]. AB - Medical treatment of cardiac arrhythmias is limited by several side effects. Haemodynamic and proarrhythmic effects are the most important limitations of antiarrhythmic drug therapy. In this paper we present data from several studies on the haemodynamic side effects of antiarrhythmic drugs of Class I and III according to Vaughan-Williams. The results were discussed with special regard to the influence of these drugs on myocardial contractility. From the results presented it is concluded that there are no important differences in the negative inotropic effects among the Class I drugs. The clinically observed more marked cardiodepressant action of some of these drugs is probably due to their unfavourable effects on pre- and afterload of the left ventricle. From a theoretical point of view, Class III drugs should have a more favourable haemodynamic profile. However, after acute administration the commercially available Class III drugs also had a cardiodepressant action. A possible explanation for this finding might be other side effects of the Class III drugs currently available, since a pure Class III drug does not exist at present. Therefore, the special haemodynamic profile of each drug should be taken into consideration for antiarrhythmic treatment. PMID- 1462676 TI - [Conventional roentgen functional diagnosis--videodensitometry. 3. Conventional roentgen videodensitometry exemplified by the heart]. AB - It is possible to record movement parameters video densitometrically and synchronously by means of a video signal analysator at various points of the organ surface visible via fluoroscopic images (provided by videorecorder). Movement parameters of the heart surface were signed just in the same cardiac action by synchronous electrocardiography. There are some difficulties in this method according to evaluation with reference to laevocardiography in consequence of functional variety of the heart and the different exercise conditions. Small aneurysms of the cardiac apex were only seen when they were separated and located at the cardiac margin. Extended cardiac aneurysms were video densitometrically recorded as a paradoxical movement at the cardiac surface. A paradoxical movement was never seen with negative findings in laevocardiography. PMID- 1462677 TI - [Protection from uv-light-induced oxidative stress by nutritional radical scavengers]. AB - Two series of examinations were carried out in two voluntary test groups for the purpose of elucidating the correlation between ultraviolet light load and oxidative stress as well as the way it is influenced by nutritive radical scavengers. After a 6 to 7-hour impact of sunshine on the whole body (sunbathing beach) at n = 8 a continuous progredient increase of thiobarbituric acid reactive substances could be identified in the serum (from 5.56 +/- 0.98 to 8.91 +/- 0.99 mumol/l, p < 0.001), which after new exposure to sunshine reached 11.3 +/- 2.4 mumol/l. Likewise, a 15-minute exposure to ultraviolet light at n = 24 induced increases of TBRS concentrations lasting from 1-2 days. After 14-day supplementation with beta-carotene (n = 6), D-alpha-tocopherol (n = 6), selenium (n = 6), and ginkgo biloba extract (n = 6) the extent of the oxidative stress could be inhibited during a second exposure to ultraviolet light up to the following efficiency: Se > Ginkgo > beta-carotene > vitamin E. The clastogenous effect of sunshine and ultraviolet light must be regarded as a factor for initiating and promoting cancerogenesis in the total organism. Concerning the aetiopathogenesis of malignant melanoma the paramagnetic properties of free radicals with their nonenergetic effects of the magnetic field have to be considered more carefully in scientific examinations. PMID- 1462678 TI - [Pravastatin, a new cholesterol synthesis inhibitor for lowering increased serum cholesterol]. AB - The association between increased risk for coronary artery disease (CAD) and elevated plasma cholesterol has been firmly established. The beneficial effect of cholesterol lowering treatment modalities was confirmed in both primary and secondary intervention trials. Because long-term treatment is usually required for lipid lowering therapies the drugs used for lipid reduction have to be not only efficacious but also safe. Inhibitors of cholesterol synthesis that have become clinically available during the last few years, can reduce plasma levels of total cholesterol and low density lipoprotein (LDL)-cholesterol very effectively. In the Familial Atherosclerosis Treatment Study (FATS) an intensive cholesterol lowering treatment modality consisting of a combination of an inhibitor of cholesterol synthesis and colestipol reduced the progression of coronary lesions and caused a partial regression of such lesions. Among the various inhibitors of cholesterol synthesis developed recently, pravastatin appears to be tissue-specific because of its hydrophilic property. PMID- 1462679 TI - [Nomination criteria in the history of the Medical Faculty of the Halle University. III. From the turn of the century to 1945]. AB - The restrictions that had remained applicable in respect of the right of nomination that had been conceded to the Departments of Universities in the 19th century, were rescinded in the early 20th century. As a rule, a list of three suggested names was submitted, but it was still possible that the ministry would issue a decree of appointment without prior approval of the relevant University department. Whereas the conventional principle of nomination continued to apply on paper, additional criteria were brought into play after 1933 involving premises determined by Nazi party politics and which resulted in centrally monitored vocational decisions. PMID- 1462680 TI - [The physician's responsibility for patient education. II]. PMID- 1462681 TI - [Skeletal development in monozygotic and dizygotic twins]. AB - The maturation and development of 27 monozygotic and 23 dizygotic twins were studied over a 10 year period with data collected at one year intervals from age 9 to adulthood. In this manner the ossification process was recorded based on X ray films of the carpal bones. Further information was acquired through anthropometric and somatoscopic data reproduced with standard photography. Sex and phase specific genetic factors influencing the maturation process are presented and analysed. PMID- 1462682 TI - Secular trends of stature and weight of Chinese girls. AB - Stature and weight were studied in 123 12-year-old Southern Chinese girls born and brought up in Hong Kong. The mean stature was 147.22 centimetres with a standard deviation of 6.65 centimetres. The mean body weight was 37.11 kilograms with the standard deviation being 7.39 kilograms. Secular trend of increased body size was demonstrated. The increase was more marked in the lower percentile groups. PMID- 1462683 TI - Estimation of age at death from second metacarpals. AB - This study examined the estimation of age at death from the second metacarpal in 227 individuals aged 30-98 years. Variables ascertained from each bone were: cortical thickness and microdensitometric cortical bone density measured on radiographs of the bone and total osteon count and density recorded on microradiographs of the complete cross section at its midshaft. Based on the latter two variables, two age groups were formed; a middle age group representing those individuals aged 30-65 years, and an older group aged 65+. Stepwise regression analysis of the four variables produced a series of regression equations for age estimation for the middle, old and combined age groups for each sex and sexes combined. Sex-specific equations provided better results than nonspecific ones, especially in females. Total osteon density and combined cortical thickness were found to be the most useful estimators in the middle and the old age group, respectively. The standard error of estimate was 6.71 and 6.90 years in each age group for the sexes combined. In the combined age group, age could be estimated accurately from total osteon count, cortical thickness and MD cortical bone density with the standard error of estimate of 11.10 years. The relative error of estimate ranged within +/- 30% in almost all individuals aged above 60 years. PMID- 1462684 TI - [Handedness in comparison with the asymmetry of the upper extremities]. AB - In 1990 221 males (88 children, age 3.5-7.25 years and 133 adults, age 20-44 years) were investigated. The sample was divided into two groups based on handedness; 140 individuals were right-handed and 81 left-handed. 10 measurements were taken at the upper limbs. In addition, marked handedness, handclasping and armfolding were determined. The last three traits showed no statistically significant connection. It was determined that measurements of length, breadth and circumference are more often significantly asymmetric in favor of the right side in right-handers than in left-handers. Further, skinfolds of right-handed individuals are larger on the left side. Partially reverse results were found for left-handers as a whole, however, the results are more irregular. A difference in the degree of asymmetry exists between children and adults. Asymmetries of breadth and circumference measurements as well as forearm skinfold are larger in adults. Taking into account the error of measurement, frequencies of R > L, R = L and L > R for right- and left-handed individuals were evaluated using the chi 2 test for significance. Preponderance of measurements on the dominant side could often be secured statistically. PMID- 1462685 TI - The formation of heart-proportion in fetal ontogenesis. AB - In the paper, the formation of basic heart proportions in the period from the 19th to 43rd week of intrauterine development was investigated. The material consisted of 1505 fetuses (930 male and 575 female). Length, width and thickness of the heart were measured to 0.1 mm on unpreserved fetus material within 24 hours after stillbirth or death, in the natural position of the organ. The material was divided into groups representing seven developmental periods, from the 5th to the 10th lunar month. Individuals from the 41st-43rd week were recognized as carried beyond term and included in the age category above the 10th month (< 10). Formation of heart proportions was investigated on the basis of a statistical analysis of the results, with both sexes considered separately. Evaluation of the research results confirmed previous results indicating a slightly different shape of the heart in the fetal period. In addition, the results show the changes that occur in heart proportions during the period of intrauterine development. A comparison of these proportions with analogous indices in adult individuals makes it possible to predict further developmental changes in the postnatal period. In comparison to the conical heart found in a grown-up individual, the fetal heart is more spherical. At the beginning of the fetal period, the length dimension of the heart is greater than its width. Beginning with the 9th month of development, a relatively slower elongation of the heart occurs in favour of a more rapid increase in its width dimension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462686 TI - Investigations on the variability of four genetic serum protein markers in Poland. AB - 198 unrelated male and female Poles from Ostrow Wielkopolski (Central Poland) and 228 unrelated male and female Kashubes from Koscierzyna (Northern Poland) have been typed for four polymorphic serum protein systems: HP, TF, GC, and PI. Phenotype and allele frequencies of all these four polymorphic systems are quite different between Poles and Kashubes. Comparisons with some other Central and East European population samples (Slovaks, Hungarians, Matyos, Gypsies) revealed a considerable genetic heterogeneity among them. Genetic distance analysis showed that Hungarians and Matyos as well as Poles and Slovaks are found in two subclusters, which are linked up to one cluster. Gypsies and especially Kashubes exhibit a distinct position from this cluster. This genetic distance pattern can be explained satisfactorily considering the ethnohistory of the population groups under study. PMID- 1462687 TI - Investigations on the variability of four genetic serum protein markers (HP; TF, GC and PI subtypes) in Italy. AB - 14 population samples from various Italian regions with a total of 2.577 unrelated male and female individuals were typed for four polymorphic serum protein polymorphisms: HP, and TF, GC and PI subtypes. The regional distribution of the allele frequencies of these four polymorphisms shows a considerable heterogeneity, which is for the most part statistically significant, thus indicating an obvious genetic variability of the population of the Italian Peninsula. PMID- 1462688 TI - [The SUVA (Swiss Accident Insurance Association) statistics and quality control]. AB - Overall quality control in medicine takes place on various levels: Physician- Hospital--Insurer--Authorities, each having different requirements. Comparative standards are rather seldom. A model for a comparative standard for insurer purposes, the medical statistics package SUMEST' is presented. This model is diagnoses oriented and includes parameters for the severity of the accident, cost of treatment and treatment outcome, all based on 5-year data pool results. PMID- 1462689 TI - [The decentralized documentation system '90' of the Study Group for Osteosynthesis Problems (AO)]. AB - The new decentralized documentation system '90' of the "Arbeitsgemeinschaft fur Osteosynthesefragen" (Association for the Study of Internal Fixation to ASIF) will be introduced. This system is used for gathering clinical data of operatively treated fractures and their clinical outcome. PMID- 1462690 TI - [Quality assurance exemplified by perinatology and surgery]. AB - Quality assurance encompasses all activities which are necessary to obtain a demanded quality of medical care. Typically, a quality assurance process ("monitoring- and evaluation-process") includes the following steps: systematic observation of quality of medical care using quality indicators, assessment of quality by comparison with standards and recognizing problems, analysis of the most important problem, realization of appropriate problem solving strategies and evaluation, if the problem is successfully solved through the corrective action. The quality assurance programs in perinatology and surgery--established in all the states of the Federal Republic of Germany--support the hospitals in the application of this quality assurance process. Uniform documentation and preparation of quality relevant information (lists of complications, profiles, charts, etc.) help the hospitals to perform a self-evaluation, to recognize problems and to verify the elimination of the problems. Hence, comparisons with local results and with results of other hospitals are possible. PMID- 1462691 TI - [Basic differential documentation as conditio sine qua non for effective quality assurance]. AB - The quality check in medicine increases not at all by judges order. This contribution shows in what point of medical-documentation quality check must begin, if she should be effective. Some examples explain, that only a discriminated and a by specialist examined basic documentation is able to give us valid statistics of clinical data. Some results of our quality checked basis documentation were presented too. PMID- 1462692 TI - [The hospital service misuse problem in orthopedics]. AB - In a representative study for all German acute hospitals the amount of inappropriate (medically not necessary) patient care was estimated. The data material, sampling design, weighting technic and the appropriateness expert rating (retrospective, consent judging) was controlled. An overall proportion of inappropriate days of care of 18.45% were found but for orthopedic diseases this rate was 31.9% and even 37.7% for the younger than 60 orthopedic patients. Similar high rates for orthopedic diseases were found in US hospital studies of inappropriateness and should lead to an analysis of their reasons. PMID- 1462693 TI - [Diagnosis--therapy and documentation]. AB - The procedures of documentation of diagnostic findings are well established--but different in their graphical and structural appearance of patients histories. Out of multiple findings a retrieval with valid informations is very clumsy. In order to increase quality a complete and reliable registration of clinical data base is necessary. For this purpose the use of electronic media is profitable if the requirements of the data-base are well defined. A nationwide agreement on one key system--including the transformation of textual structures--is proposed. Only this way leads to comparable results in therapeutic procedures. PMID- 1462695 TI - [Analysis of errors in ICD 9 diagnostic classification in compliance with the Federal health care regulation]. AB - In the present study the diagnosis from 1221 letters of discharge of the years 1986 and 1987 were additionally coded by the documentation doctor of the orthopaedic department and compared with the documentation sheets and the computer lists of the administration. Supplementary to this after one year there was carried out an additional coding of the letters by the documentation doctor. The transfer errors of the administration were amounting to 1.72 p.c. with regard to three digit numbers and to 11.87 p.c. with regard to four digit coding. During the repeated examination the documentation doctor made an error of 4.3 p.c. for the three digit coding and of 15.6 p.c. if the maximum coding was required. The corresponding errors of the house physicians for three digit numbers (maximum) were amounting to 8 p.c. (33.6 p.c.) for frequent diagnoses, to 28 p.c. (48.5 p.c.) for rare diagnoses and totally 13.7 p.c. (37.8 p.c.). In the present documentation validity and reliability still shows a good result compared to other studies. Nevertheless a documentation with an error rate to such an extend is of no use for a base documentation, and this error rate must be taken into consideration in the interpretation of global medical statistics. Automatic coding systems integrated into medical writing service seems to be the only help in view of removing these problems. PMID- 1462694 TI - [Analysis and assurance of complete medical documentation]. AB - A written report on the findings of the examination forms the basis for the further procedure in the treatment of a patient--not merely in the area of orthopaedics. The examination findings should, therefore, be legible, readily understandable and complete. On the basis of 600 individual findings established at admission in the case of inpatients with diseases of the spine and hip, stemming from a total of three hospitals, the behaviour pattern of the individual examiner is analysed along with deficiencies in documentation. For a number of significant deficits, differences in the particular emphasis applied by individual physicians during the examination, the fact that the time available for such examinations is usually limited, and the lack of documentation system, are probably responsible. PMID- 1462696 TI - [Additional coding for legally required ICD-9 as the basis for high quality patient record searches]. AB - We are convinced, that the updating of the ID DIACOS diagnosis catalogue fits better to the today's medical language, than the former one. By using a consequent additional code we could eliminate several lacks of the ICD-9. Valid and reproducible diagnosis statistics are now possible. Subjective coding mistakes are largely avoidable. Inquiries of certain diagnosis can be answered by using the one of the two codes, that describes the diagnosis in the best form. Regarding the allotments of the best form. Regarding the allotments of the catalogue of orthopedic and traumatic diagnosis including the possibility of double-coding we got a special better version of ID DIACOS than before. PMID- 1462697 TI - [Basic medical documentation with ID DIACOS as an instrument for quality assurance]. AB - Standardized methods and instruments of medical documentation are prerequisites for quality assurance in medicine. Support for quality assurance measures at present can be attained by the programme systems ID DIACOS (encoding of diagnoses into ICD-9 and procedures into ICPM-GE) for daily clinical routine documentation. Administrative statistics, e.g. the L1-statistics of diagnoses according to section 16 Federal Statutory Instrument on Hospital Care Rates (BPflV) can be compiled without waste by aggregation. Supplementations of the programme system are planned caused by the introduction of new forms of Hospital reimbursement with changed classification patterns. An increasing need for computer-aided encoding will also result by the implementation of new classifications, e.g. ICD 10 and by the requirements concerning a scientific basic documentation (Selbmann, 1990; Mau, 1990) based partly on nomenclatures. The connection of the programme systems ID DIACOS and SNOMED (empirical and morphological analysis of medical texts) is possible and will be carried out (Hultsch, Diekmann, Ruhl, 1990). PMID- 1462698 TI - [Electronic data processing-assisted standardization of medical documentation]. PMID- 1462699 TI - [Medical applications of electronic data processing in surgery, trauma surgery and orthopedics. Results of a survey of 1,450 clinics]. AB - With a standardized questionnaire we evaluated 1450 orthopedic and general surgery departments. The response rate was 57.2%, 52% of the departments were using computers for different purposes. The favoured system was the MS-DOS system (73%). The computers were mainly used for word processing (58%), statistics (50%), and graphics (39%). For clinical routine the leading use was patient documentation (70%) followed by patient report generation (43%). Other applications (e.g. online use of administrative data (19.4%) or the use of other patient information like blood parameters (10%)) were relatively rarely used. However, most of the users have plans to incorporate these applications in the nearest future. For the out patients care the leading application is private billing (42.5%) and statistics (30%). The majority of the departments (42.6%) only have one PC. Most of the departments use the printer for hard copies and as hard disc a the standard storage medium. The average storage capacity of the used hard discs is 40 to 80 MB. Other peripheral tools like a laser printer, a scanner, or modems are rarely used. Most of the departments invested between 5000 and 15,000,--DM. 33.3% financed the computers only with the official budget of the department. However, 25.8% only used private funds to buy the hard- and software. The distribution according to zip codes showed a slight accommodation in Bavaria and NRW. The amount of new installations showed an almost constant increase from 1975 until 1981. Between 1981 and 1990 there was a significant increase with a small drop in 1986. PMID- 1462700 TI - [Long-term results of epicondylitis humeri ulnaris ("golfer's elbow") after treatment analogous to Hohmann's incision of epicondylitis humeri radialis ("tennis elbow")]. AB - With an average follow-up of 6.1 years the results of Hohmann's operation in treatment of humeri ulnaris epicondylitis in 23 cases are presented. For evaluation a numerical rating system with subjective and objective criteria was designed. The results were excellent in 43.5%, good in 26.1% and fair in 17.5% by subjective and excellent in 47.9%, good in 26.1% and fair in 13% by objective evaluation. Three cases had a poor result. The study reviews causes, clinical tests, conservative treatment and our operative method. PMID- 1462701 TI - [Arthroscopic subacromial decompression. 1-3 year results]. AB - In 148 patients with impingement lesion type I or type II, we performed an arthroscopic subacromial decompression (ASD). 122 patients ran a follow up one to three years post-operatively. All patients were pre- and postoperatively documented by a 100 point shoulder score. The mean score was 57.9 (+/- 11.5) preoperatively. Postoperatively there was a significant increase to 80.7 (+/- 17.9) (p < 0.05). 15% of the patients with a postoperative score less than 70 points were determined as failures. Patients with a preoperative pain history of more than one year had a significantly worse result (79.1 +/- 8.4) compared to those patients with a preoperative course less than one year (88.8 +/- 11.6) (p < 0.05). Other significant factors were the patient's age, and calcific tendinitis, whereas sex, preoperative range of motion, muscle atrophy, and degeneration of the acromioclavicular joint did not significantly influence the result. Our results after ASD in patients with subacromial pathology without a rupture of the rotator cuff are encouraging. Therefore, ASD seems to be a reasonable alternative to open acromioplasty. PMID- 1462702 TI - [Pathogenesis and prevention of spastic hip dislocation]. AB - Based on retrospective analysis of 82 hips of 41 patients with cerebral palsy, a pathogenetic model of spastic paralytic dislocation of the hip is introduced including recent observations of the normal hip development. According to this model the reduced activity of the gluteus maximus, medius, minimus and quadriceps femoris muscles, which normally cause a decrease of valgus and anteversion, results in an increased subluxating coxa valga antetorta with a consecutive dislocation. In order to prevent a dislocation, these muscle groups have to undergo increased activation. Since walking has to be to undergo increased activation. Since walking has to be considered the strongest stimulus for the dislocation-preventing hip abductors, hip extensors, outward rotators and knee extensors, the erect gait should be encouraged with statomotorically favored children early as possible. This can be supported by muscle relaxing surgery of the antagonistically effective hip flexors, hip adductors and inward rotators as well as the knee flexors. These muscle release operations will counteract, although to a limited extent, a dislocation even with a severely handicapped child who is unable to walk. PMID- 1462703 TI - [Surgical treatment of hip dislocation in patients with infantile cerebral palsy]. AB - The results of 63 operations on 52 patients with cerebral palsy, which were performed between 1978 and 1988 to correct a subluxation or dislocation of the hip, were reviewed. The innominate pelvic osteotomy was preferably combined with intertrochanteric femoral osteotomy and soft tissue release. The average age at time of surgery was 7 years/2 months. Surgical intervention was indicated irrespective of the severity of neurologic involvement. The mean follow-up period is 3 years/4 months. The results show, that by a combinations of these surgical procedures a permanent stability of the hip joint can be achieved. Retrospectively the 5 cases of reluxation can be explained by insufficient surgical technique. The postoperative development of the CE-angle and the acetabular index reveal, that after adequate reduction of the femoral head the acetabulum is able to remodel its dysplasia. From a functional point of view actually patients with diplegia gained the most benefit from a stable hip joint, because they showed the most progress in motor activity. In tetraplegic patients the long-term success of these surgical procedures must be seen in the prevention of a painful hip in adult life, the maintenance of sitting-stability and the improvement of perineal care condition. PMID- 1462704 TI - [Postoperative infections and wound healing disorders in patients with infantile cerebral palsy]. AB - As part of a retrospective study including 569 patients with ICP and a group of 405 controls, the risk of postoperative wound healing disorders and wound infections was investigated in surgically treated children with cerebral palsy. The higher rate of wound healing disorders in ICP patients could not be attributed to factors such as excessively long duration of operation, secondary interventions, or a high number of interventions per operation. Rather, the causes of the increased risk of infection have to be seen in connection with the symptoms of ICP itself, such as immunological weakness, increased tendency to sweat, reduced circulation in the affected extremity and disturbances of sensitivity and perception. A direct link between these parameters and increased risk of postoperative infection can only be established by prospective studies. PMID- 1462705 TI - On-line coupled liquid chromatography-gas chromatography (LC-GC) and LC-LC-GC for detecting irradiation of fat-containing foods. AB - On-line coupled liquid chromatography-gas chromatography-flame ionisation detection (LC-GC-FID) enables efficient and unambiguous determination of irradiation for some fat-containing foods (e.g. meat). Other products, however, contain interfering components or are contaminated, e.g., with mineral oil. Since more selective detection by mass spectrometry has limited success, the determination was improved by a more selective isolation of some key components among the fat degradation products, e.g. the dienes or trienes, by LC-LC-GC-FID. Applications are shown for soup mixes, some spices, fish, and shrimps. PMID- 1462706 TI - Determination of the heating temperature of fishery products. AB - The German Fish Directive prescribes that products must be heated to the core temperature of +70 degrees C to kill existing larvae of nematodes. For subsequent determination of the heating temperature samples were extracted with water. The extracts were analysed for protein content, for protein patterns obtained by isoelectric focusing and by using the coagulation test. The suitability of these methods was investigated with heated extracts, heated minced fish flesh, and smoked herring and mackerel. Smoking was performed in the kiln of the institute at controlled temperatures. Analysis of commercial samples showed that the core temperature during smoking of herring and mackerel must have been clearly below 70 degrees C in several cases. PMID- 1462707 TI - Macroelements content of Common Pacific squid (Loligo opalescens). AB - The macroelement (sodium, potassium, calcium and magnesium) concentrations have been determined in various tissues of the Common Pacific squid, Loligo opalescens. The method of measurement was flame atomic emission (sodium and potassium) and absorption (calcium and magnesium) spectrometry. Edible tissues such as the tube (mantle), arms and crown, and fin contained: from 3.3 +/- 0.4 to 3.9 +/- 1.5 (1.9-6.8) g/kg wet weight of sodium; from 5.3 +/- 0.6 to 6.3 +/- 2.7 (3.3-14) g/kg of potassium; 38 +/- 7 to 100 +/- 34 (28-200) mg/kg of calcium; and from 510 +/- 100 to 950 +/- 280 (340-1500) mg/kg of magnesium. The other tissues or organs examined frequently contained a higher concentration of macroelements than the edible flesh. Statistically significant correlations between the body weight of squid and macroelement concentrations or between some pairs of metals in whole squid, mantle and hepatopancreas have been observed. PMID- 1462708 TI - [Comparative studies of the Osborne protein fraction of wheat varieties with different dough and baking properties]. AB - The proteins of flours from the wheat varieties Clement (CLE) and Disponent (DIS), which are characterized by substitution of the wheat chromosome 1B by the rye chromosome 1R (CLE) and by 1BL/1RS-translocation of chromosome segments (DIS), respectively, and which yield sticky doughs, were extracted by the Osborne procedure and compared with the good variety Kolibri (KOL). CLE and DIS delivered significantly higher amounts of water-soluble proteins (31.2 and 23.2% of the total protein) than KOL (15.5%). The proportions of ethanol-soluble proteins were approximately constant for the three varieties (31.5-33.9%) while the amounts of residual proteins after extraction with ethanol were significantly different (CLE, 16.8%; DIS, 21.6%; KOL, 26.4%). Water extracts as well as residues exhibited also marked differences in their amino acid compositions. Investigation of the water extract from DIS by gel permeation chromatography and by RP-HPLC showed the presence of prolamins: omega 1,2-gliadins and/or omega-secalins could be detected on the basis of amino acid composition and N-terminal amino acid sequence. In the case of good varieties such as KOL, these prolamins seem to remain partially in the residue of the ethanol extract under the conditions of the classical Osborne procedure, whereas they are found in the water extract in the case of such varieties as CLE and DIS. On the other hand, a modified Osborne procedure (salt/ethanol/acetic acid) delivered the prolamins, which correspond to 39-40% of the total protein, completely within the ethanol fraction in the case of all three varieties.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462709 TI - Application of polyuronides for removing heavy metals from vegetable oils. III. Application of alginic acid, pectic and pectinic acids for demetalization of hydrogenated sunflower oil. AB - Laboratory experiments have been carried out for the removal of heavy metals from hydrogenated vegetable oils using hydrated polyuronides (degree of swelling from 4 to 12.8 ml/g) such as alginic acid, pectic and pectinic acids. The effect of the type of polyuronide, degree of esterification and oil treatment on the degree of demetalization has been studied. It has been shown that with increase in the degree of esterification of the polyuronide the efficiency of demetalization decreases. The second and third treatment of the hydrogenated oil with pectinic acid resulted in a high degree of heavy metal removal. The possibility of efficient demetalization of hydrogenated oils by treatment with water solutions of pectinic acids has also been demonstrated. The degree of metal ion removal increases with decreasing concentration of pectinic acids in the water solution. PMID- 1462710 TI - Influence of demetallization of hydrogenated sunflower oil on changes in the forms of heavy metals and their pro-oxidative effects. AB - The effect of removing heavy metals from hydrogenated sunflower oil using a method based on changes in the contents of the various forms of the heavy metals copper, iron, zinc and nickel and their respective pro-oxidative effects was studied. A high degree of removal of dissociated and bounded ions was observed for hydrogenated oil, while there was no change in the contents of the co ordination form. The pro-oxidative effect of the dissociated ions and of the bound metal ions in hydrogenated oil decreased nine-fold and seven-fold, respectively, compared with that of the non-hydrogenated oil, as a result of which the oxidation stability of hydrogenated oil increased two-fold. Comparative studies confirmed as appropriate the use of wash waters and auxiliary solutions that do not contain heavy metals for the processing of the hydrogenate after the classical technology. PMID- 1462711 TI - Tuberculosis and AIDS: European and worldwide perspectives. AB - To examine the possible influence of AIDS and HIV infection on the epidemiology of tuberculosis in Europe and worldwide in the coming decades an analysis of the available data on the two diseases and on the transmission of the two infections in relation to the demographic structure of the population was conducted, including projections for up to the year 2025. Globally, the effects of the AIDS pandemic on the tuberculosis situation will probably be very serious, adding some 1.5 million new cases of tuberculosis annually by the year 2025 as a result of HIV infection. However, this effect for Europe in the year 2025 may be in the range of 15,000 additional cases only. The main factor determining the scale of aggravation of Tb is the age structure of the population infected, or at risk of being infected, with tubercle bacilli and HIV. Although the influence of HIV infection on tuberculosis in Europe may not be very high due to the fact that HIV infection involves mainly younger age groups it may, however, substantially postpone the elimination of tuberculosis from Europe. Therefore it seems necessary to monitor constantly all the changes in the epidemiological situation of both tuberculosis and AIDS/HIV. PMID- 1462712 TI - [HIV infection: feasibility of a seroprevalence study with consent of hospitalized patients]. AB - A pilot study was carried out in order to evaluate the feasibility of determining the seroprevalence rate of HIV infection and the prevalence of risk factors among selected hospital patients at the Centre Hospitalier Universitaire Vaudois (CHUV). Consent was obtained and only blood already obtained for other purposes was used for testing. Among 850 patients between 16 and 65 years of age and residing in Switzerland who were originally selected at random, only 200 patients were accessible for an interview and for whom blood was available in order to be included in the study. Of these, 165 (83%) accepted their blood to be tested. A seropositive result was identified in 2 patients already aware of their serostatus. The age distribution, diagnosis and behavioral risk factors (when available through the interview) were not different among those accepting the test and the ones refusing. However, foreigners were more likely to refuse the blood test than Swiss nationals, even though none of them came from a country with a high rate of endemicity for HIV infection. Reasons for refusal included the following: lack of risk factors 10 (29%), doubts about confidentiality 6 (17%), blood test already performed 5 (14%), language barrier 4 (11%) and others 10 (29%). We conclude that even though the data in our sample did not suggest that patients refusing the test were at an increased risk of being seropositive, it is unlikely that with such a refusal rate, a reliable measure of seroprevalence could be determined in the population of study with the methods used, especially when one is expecting a relatively low seroprevalence rate. PMID- 1462713 TI - Infertility in industrialized countries: prevalence and prevention. AB - We discuss the prevalence and aetiology of infertility and the relevance of this information for national infertility services and prevention programmes. The prevalence of infertility in industrialized countries has been said to be as high as 10-20%. This estimate, and the argument that little can be done to prevent infertility, have been used as justification for increased government investment in, or expansion of, services for medically assisted conception. However, population prevalence surveys indicate that far fewer couples of reproductive age are actually infertile. For example, a recent survey in the United States reported that 8.5% of married couples with a wife age 15-44 were infertile. 4% of the sample were childless and reported having a condition which impaired fecundity, while less than 2% were childless, had impaired fecundity and were over 35 years of age. Other studies show that nearly a third of couples have difficulty conceiving at some point during their reproductive lives but few actually remain childless. A significant proportion of infertility could be prevented through more aggressive application of standard public health measures. PMID- 1462714 TI - Community involvement towards community objectives. AB - The World Health Organisation "Health for all children by the year 2000" declaration presents an exciting yet timely challenge. If these aims are to be achieved, the role of the health worker must be broadened. There must be a recognition that families will determine the true health of their children- physical, mental and social. Families must be able to identify and realise their aspirations, to satisfy their needs and to cope with and adapt to their environments. Only by advocacy, by forming a partnership with families, and by empowering families to exercise greater control over their health and their environment, will health workers begin to see positive change in the community. There is a need to collect and collate data from the community in order that the true needs of families are met. New outcome measures which address "quality of life" must be developed; these will accord closely with the WHO aims, and will enable communities to set the high standards that must be achieved for our children. "Health", interpreted in its broadest meaning, should lead to health professionals concentrating on the promotion of a healthy lifestyle and the attainment of "quality of life". There must be a move away from the "medical model" of care to the empowerment of parents who are responsible for the care for their children and the need to work towards better community resources. PMID- 1462715 TI - [Therapy for smoking: consensus in German-speaking countries]. AB - The german speaking countries (Austria, Germany, Switzerland) are not the most advanced in the world when it comes to the control of tobacco related diseases. The medical system in these countries has yet to be convinced that smoking cessation is not only necessary but feasible. In order to provide a basic document for further activities, a consensus development process was initiated. The consensus development process forms part of the activities performed by the UICC (International Union Against Cancer) Project Smoking Cessation, which is a project within the framework of the UICC Tobacco and Cancer Programme. The 1988 Report of the US Surgeon General states very clearly, that the use of tobacco products is not a matter of free choice, but is the result of an addiction as scientifically valid as the addiction to heroin and other narcotics. The scientific literature provides informations on many methods and techniques for a smoking cessation, both pharmacological and non-pharmacological. Many pharmacological approaches have been tried to treat nicotine dependence in man. According to scientific standards and many controlled studies, nicotine has been the only drug found to be effective in treating nicotine dependence. Many techniques, ranging from self help to sophisticated combined therapeutic approaches including pharmacological interventions, are now available to deal with the nicotine addiction. Smoking cessation treatment uses time, effort and other resources and the question of reimbursement for these services has to be considered. As with any other form of treatment, costs needed to be paid either by the individual patient/client and/or by other sources including private and national health insurance systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462716 TI - Different frequencies of diabetic complications in insulin-treated patients with diabetes of comparable duration, in relation to age at onset of diabetes. AB - Diabetic complications such as retinopathy and nephropathy affect the quality of life of diabetic patients. The aim of this study was to find out whether there are differences in the development of these complications associated with the age at onset of diabetes and the different effects of diabetes onset before, during or after puberty. Therefore, we tested the hypothesis whether onset of insulin dependent diabetes in puberty was connected with an increased risk of developing diabetic microangiopathy. We found a significantly increased risk in patients with diabetes onset in puberty up to a diabetes duration of 20 years if compared with diabetes onset before but not with that after puberty. It seems that diabetes onset before puberty delays the development of early diabetic complications and that changes of the hormonal status during puberty may be responsible for an earlier development of retinopathy. After about 20 years of diabetes there are no significant differences between the groups. Our results emphasize the necessity of early ophthalmological diagnosis and adequate metabolic control, especially in patients with diabetes onset during or after puberty, in order to prevent or delay the development of diabetic complications. PMID- 1462717 TI - AIDS surveillance in Europe: status at 31st March 1992. European centre for the epidemiological monitoring of AIDS. PMID- 1462718 TI - European community concerted action on monitoring HIV seroprevalence in a sentinel population of STD patients (June 1990-December 1991). PMID- 1462719 TI - Steep decline in world fertility rates: contraceptive use up sharply. PMID- 1462720 TI - Prevalence of mycoplasmas in the respiratory tracts of pneumonic calves. AB - The prevalence of mycoplasmas in the respiratory tracts of 148 pneumonic calves originating from 25 herds in the Netherlands is reported. Four types of culture media were used to isolate mycoplasmas: solid modified Edward medium, 2 types of Friis media, and A7B differential agar medium. Mycoplasmas were isolated both from nasal swab specimens and lung lavage fluids collected from live calves and from nasal mucosa and lung tissue specimens collected post mortem. All of the mycoplasma strains isolated could be identified as either Ureaplasma diversum (isolated from 80% of 25 herds), Mycoplasma dispar (92%), M. bovirhinis (88%), M. bovis (20%), M. bovigenitalium (4%), M. arginini (16%), or M. canis (12%). Isolation rates of M. dispar and U. diversum were considerably higher from lung lavage fluids than from nasal swab specimens. M. bovis was detected only in fattening herds and not in dairy herds. The respiratory tracts of 75% of the calves examined contained at least 2 mycoplasma species. In total, 25 different combinations of mycoplasma species were detected in specimens collected from noses and lungs. The pathogenic species U. diversum and M. dispar had not been isolated before in the Netherlands. PMID- 1462721 TI - Antibody responses to natural Dictyocaulus viviparus exposure in first year grazing cattle using vaccination or different kinds of anthelmintic treatment. AB - In two field trials vaccination or different anthelmintic treatments against Dictyocaulus viviparus infections were used in 6 groups of first year grazing cattle. The antibody response to lungworm infections was determined using an ELISA. Cattle treated once or repeatedly at long intervals with levamisole developed clinical signs of dictyocaulosis. The detection of anti-D. viviparus antibodies at the end of the grazing season confirmed that these anthelmintic treatments were not able to prevent lungworm infections. Cattle that received strategically administered treatments with ivermectin remained clinically healthy. These cattle were seronegative until the end of the trial which proved the efficacy of the strategic control. Cattle that received an intraruminal slow release bolus did not develop clinical disease. However one animal shed lungworm larvae and the herd became seropositive at the end of the grazing season indicating a history of infection. The serological examination of a cattle herd at the end of the grazing season is able to demonstrate a history of lungworm infections and to determine the efficacy of anthelmintic control measures. PMID- 1462722 TI - Canine distemper with spinal cord lesions. AB - A case of distemper in a 6-month-old dog is described. The dog was presented with a history of tetraparesis suggestive of trauma. Neurological examination and clinical pathology findings of lymphopenia and pleocytosis suggested a viral cause. Microscopic findings of a nonsuppurative meningoencephalomyelitis with numerous intranuclear inclusions in the cerebellum, brain stem, and all parts of the spinal cord suggested a diagnosis of distemper. PMID- 1462723 TI - [Infections with enteropathogenic Escherichia coli (EPEC) in cattle. 1. Comparison of different animal models and a cell culture system for the establishment of a detection system for "attaching and effacing" (AE) lesions]. AB - In several animals species, enteropathogenic Escherichia coli (EPEC) were described as agents causing diarrhea. The histopathogenic pattern of EPEC is due to a typical adherence to enterocytes, called "attaching and effacing" (AE). This lesions are characterized by the formation of pedestals, cups and a marked loss of microvilli on enterocytes. In view of using an "in vitro system" (HeLa-cell culture) to test the adherence of EPEC, we first tested bovine EPEC in several laboratory animals. Various strains of mice, one day chicks (peroral) and a three day old calf (ligated intestinal loops) were inoculated with a bovine pathogenic EPEC (S 102-9). The adherence of EPEC "in vivo" was histologically, electron microscopically and bacteriologically investigated and compared to adherence to HeLa cell cultures. AE-lesions were found on calf enterocytes as well as on HeLa cells, no lesions were seen in mice and chicks. The ligated intestinal loop test seems to be a useful model to compare "in vivo" to "in vitro" adherence. PMID- 1462724 TI - Identification of a cyprinid fish, the tench Tinca tinca L., as a carrier of the bacterium Aeromonas salmonicida, causative agent of furunculosis in salmonids. AB - A typical, pigment-producing strain of Aeromonas salmonicida (A. sal.), the causative agent of furunculosis in salmonid fish species, was isolated from a cyprinid species, the tench Tinca tinca L. with papilloma-like skin alterations. Histopathology of the papilloma-like skin alterations in tench revealed "round holes", distinctly lined by thick layers of epithelial cells, but no bacteria. The organism was isolated from skin, gills and fins, but not internal organs. The isolate proved highly virulent for both juvenile tench and brown trout Salmo trutta L. in experimental infection, but it did not reproduce the clinical picture. The causative role of A. sal. for the surface lesions remains questionable. However, there is a perceived risk of the organism's transmission between tench and other susceptible species of fish, especially farmed trout. PMID- 1462725 TI - Bacillary haemoglobinuria diagnosis by the peroxidase-antiperoxidase (PAP) technique. AB - A peroxidase-antiperoxidase (PAP) technique was used to diagnose bacillary haemoglobinuria in formalin-fixed, paraffin-embedded liver tissues of cattle. The PAP method revealed Clostridium haemolyticum in the zone of liver necrosis characteristic of the disease and also in culture smears of this microorganism, but C. novyi type B, C. chauvoei, C. septicum and C. perfringens types B and C remained unstained by the PAP reaction. The PAP technique performed provides a specific, simple and rapid method to diagnose bacillary haemoglobinuria. PMID- 1462726 TI - The nasal mycoplasmal flora of healthy calves and cows. AB - The nasal mycoplasmal flora of 270 healthy cows from 27 herds in the Netherlands and 35 healthy calves from 7 of these herds was examined. Various methods for isolating mycoplasmas were compared. The prevalence of the various species was as follows: Ureaplasma diversum in 3 (9%) calves; Mycoplasma dispar in 14 (40%) calves; M. bovis in 1 (3%) calf; M. bovirhinis in 23 (66%) calves and 16 (6%) cows; M. bovoculi in 8 (23%) calves and 53 (20%) cows; M. canis in 1 (3%) calf; M. equirhinis in 2 (1%) cows; M. conjunctivae in 2 (1%) cows; Acholeplasma laidlawii in 1 (3%) calf and 3 (1%) cows; and A. axanthum in 7 (3%) cows. The noses of healthy calves were less frequently colonized by the pathogenic species U. diversum and contained fewer U. diversum and M. dispar organisms than the noses of pneumonic calves. We concluded that the mycoplasmal flora of calves and healthy cows was quite different and also that cows play only a minor role in the epidemiology of pathogenic mycoplasma species of calves in the Netherlands. PMID- 1462727 TI - Studies on the application of enzyme immunoassays for the Fusarium mycotoxins deoxynivalenol, 3-acetyldeoxynivalenol, and zearalenone. AB - Polyclonal antisera against zearalenone (ZEA) were produced in rabbits after immunization with ZEA-oxime coupled to human serum albumin. Using these antibodies and a ZEA-oxime-horseradish peroxidase conjugate in a competitive direct enzyme immunoassay (EIA), the detection limit for ZEA was 70 pg/ml. The relative cross-reactivities of the assay with ZEA, alpha-zearalenol, beta zearalenol, zearalanone, alpha-zearalanol, and beta-zearalanol, respectively, were 100%, 37.3%, 7.2%, 59.2%, 5.3%, and 3.9%, respectively. This EIA and two EIAs for deoxynivalenol (DON) and 3-acetyldeoxynivalenol(3-AcDON) (Usleber et al., 1991) were used to analyze wheat samples. The limits of determination for DON, 3-AcDON, and ZEA in wheat were 200 ppb, 50 ppb, and 20 ppb, respectively. The analysis of reference materials (wheat flour) containing DON by EIA showed good agreement with the nominal values. The EIA for ZEA was in addition used to analyze biological fluids, obtained during a feeding trial. Two lactating cows were administered 25 mg and 100 mg ZEA per day, respectively, over a period of 6 days. Serum, milk, urine, and feces were assayed in the ZEA-EIA with and without sample treatment with beta-glucuronidase prior to the analysis. Maximum toxin levels (ZEA-equivalents) found in milk were 0.4 and 1.2 ppb (glucuronides). The toxin concentration in milk decreased rapidly after the last toxin administration. In the urine, maximum levels of toxin-glucuronide conjugates were 23 ppb and 24 ppb, respectively. The serum toxin levels corresponded to those found in milk. In the feces, mean values were 150 ppb and 500 ppb, respectively, no conjugated toxins were found in feces. PMID- 1462728 TI - Modelling of in vivo calcium metabolism. II. Minimal structure or maximum dynamic diversity: the interplay of biological constraints. AB - The temporal behaviour of the nonlinear compartmental model we have developed for rat calcium metabolism is discussed with respect to the theoretical properties of the self-oscillating autocatalytic subunit around which the model is constructed. Depending on the approximations made, this subunit is described by a minimal two variable model, SU2, or by a three-variable one, SU3. The diversity of the theoretical dynamic behaviours possible with SU2 is greatly increased with SU3. But the identification of SU3 parameter values in three different experimental situations reveals that biological constraints efficiently preserve a simple circadian rhythm for bone metabolism. This analysis indicates the significant contribution of the available bone crystal pool to the dynamic organization of this tissue, and hence to extracellular calcium homeostasis. PMID- 1462729 TI - On the existence and the role of chaotic processes in the nervous system. AB - Chaos theory is a rapidly growing field. As a technical term, "chaos" refers to deterministic but unpredictable processes being sensitively dependent upon initial conditions. Neurobiological models and experimental results are very complicated and some research groups have tried to pursue the "neuronal chaos". Babloyantz's group has studied the fractal dimension (d) of electroencephalograms (EEG) in various physiological and pathological states. From deep sleep (d = 4) to full awakening (d > 8), a hierarchy of "strange" attractors paralles the hierarchy of states of consciousness. In epilepsy (petit mal), despite the turbulent aspect of a seizure, the attractor dimension was near to 2. In Creutzfeld-Jacob disease, the regular EEG activity corresponded to an attractor dimension less than the one measured in deep sleep. Is it healthy to be chaotic? An "active desynchronisation" could be favourable to a physiological system. Rapp's group reported variations of fractal dimension according to particular tasks. During a mental arithmetic task, this dimension increased. In another task, a P300 fractal index decreased when a target was identified. It is clear that the EEG is not representing noise. Its underlying dynamics depends on only a few degrees of freedom despite yet it is difficult to compute accurately the relevant parameters. What is the cognitive role of such a chaotic dynamics? Freeman has studied the olfactory bulb in rabbits and rats for 15 years. Multi electrode recordings of a few mm2 showed a chaotic hierarchy from deep anaesthesia to alert state. When an animal identified a previously learned odour, the fractal dimension of the dynamics dropped off (near limit cycles).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462730 TI - Application of the metabolic control theory to the study of the dynamics of substrate cycles. AB - Substrate cycles are ubiquitous structures of the cellular metabolism (e.g. Krebs cycle, fatty acids beta-oxydation cycles, etc...). Moiety-conserved cycles (e.g. adenine nucleotides and NADH/NAD, etc...) are also important. The role played by such cycles in the metabolism and its regulation is not clearly understood so far. However, it was shown that these cycles can generate multistationarity (bistability), irreversible transitions, enhancement of sensitivity, temporal oscillations and chaotic motions (Hervagault & Canu, 1987; Hervagault & Cimino, 1989; Reich & Sel'kov, 1981; Ricard & Soulie, 1982). [formula: see text] Fig. 1: Scheme of the open binary substrate cycle under study. The substrate S is converted into P with a net rate v2. Substrate P is converted in turn into S with a net rate v3. Step v2 is inhibited by excess of the substrate, S. In addition, the cycle operates under open conditions, that is zero-order input of S at rates alpha 0(v1) and first order outputs of S and P at rates alpha S and alpha P(v4), respectively. The metabolic control theory (see also Fell, 1990), which shows how a metabolic network reacts to small perturbations in the vicinity of a steady state, and is formulated with the so-called "control coefficients", was applied to such a cycle in order to get a better knowledge on the importance of each step at the regulatory point of view. The behaviour of a binary substrate cycle (fig. 1) in which one of the enzymes may be subjected to inhibition by excess of its substrate (v2) was studied theoretically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462731 TI - Flow cytometric analysis of the cell cycle: mathematical modeling and biological interpretation. AB - Estimation of the repartition of asynchronous cells in the cell cycle can be explained by two hypotheses: the cells are supposed to be distributed into three groups: cells with a 2c DNA content (G0/1 phase), cells with a 4c DNA content (G2 + M phase) and cells with a DNA content ranging from 2c to 4c (S phase); there is a linear relationship between the amount of fluorescence emitted by the fluorescent probe which reveals the DNA and the DNA content. According to these hypotheses, the cell cycle can be represented by the following equation: [formula: see text] All the solutions for this equation are approximations. Non parametric methods (or graphical methods: rectangle, peak reflect) only use one or two phase(s) of the cell cycle, the remaining phase(s) being estimated by exclusion. In parametric methods (Dean & Jett, Baisch II, Fried), the DNAT(x) distribution is supposed to be known and is composed of two gaussians (representative of G0/1 and G2 + M) and a P(x,y) function representative of S phase. Despite the generality, these models are not applicable to all sample types, particularly heterogeneous cell populations with various DNA content. In addition, the cell cycle is dependent on several regulation points (transition from quiescence to proliferation, DNA synthesis initiation, mitosis induction) and biological perturbations can also lead to cytokinesis perturbations. Before the emergence of flow cytometry, the current view of cell cycle resided in the assessment of cell proliferation (increase in cell number) or the kinetic of molecules incorporation (DNA precursors).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462732 TI - Measurement of efflux from G1-phase in a growth factor dependent cell line. AB - In order to test a mathematical model of G1/S-phase transition, the proliferative response of the murine myeloid interleukin 3 (IL-3) dependent cell line NFS-78 to graded reduction of IL-3 levels was measured. Exponentially growing cells were exposed to bromodeoxyuridine (BUdR), which replaces thymidine (TdR) in the DNA double strands during DNA synthesis. After incubation periods ranging from 3 to 36 h the cells were fixed and stained with a fluorescence dye mixture of Hoechst 33258 and ethidium bromide (EB) and subsequently analyzed in a two-parametrical flow cytometer. The BUdR-quenched TdR-specific Hoechst 33258 fluorescence of each cell provides information on the cell cycle location at the start of incubation and on whether or not a cell has divided. The DNA-specific EB fluorescence provides information on the actual cell cycle location at the end of the incubation period. From the 2-dimensional fluorescence distributions the efflux from G1-phase was calculated. Upon IL-3 reduction the cells showed accumulation in the G1-phase along with a reduction in the progression rate through the other phases of the cell cycle. By staining with the vital dye Hoechst 33342 as well as with propidium iodide (PI) it was further possible to show that cell death after IL-3 withdrawal occurred in all phases of the cell cycle. PMID- 1462733 TI - Growth factors and cell kinetics: a mathematical model applied to Il-3 deprivation on leukemic cell lines. AB - We assume the existence of a specific G1 protein which is an initiator of DNA replication. This initiator is supposed to be synthesized according to Michaelis Menten kinetics. In order to start DNA replication, it is assumed that this G1 specific protein must be produced in a required amount. Intra-cellular growth inhibitors and extra-cellular growth factors control the production of the initiator. This model allows to calculate the average G1 phase time as a function of the various chemical concentrations of nutrients, enzymes, growth inhibitors and growth factors. This model is compared to cell kinetics experiments on a leukemic cell line responding to Interleukin 3 deprivation. The curves giving the experimental average G1 phase times with respect to Interleukin-3 concentrations are fitted by the mathematical model with a quite good agreement. PMID- 1462734 TI - Interpretation of epicardial mapping by means of computer simulations: applications to calcium, lidocaine and to BRL 34915. AB - The aim of this work was to compare experimental investigations on effects of lidocaine, calcium and, BRL 34915 on reentries to simulated data obtained by use of a model of propagation based on the Huygens' construction method already described in previous works. Calcium and lidocaine effects are investigated on anisotropic conduction conditions. In both cases, reduction in conduction velocities are observed. In lidocaine case, a refractory area is located along the longitudinal axis. In agreement with experimental electrical mapping, the simulations show that the stabilization of reentrant excitation is mainly due to the existence of this refractory area around which the reentrant circuit can develop. The experimental study shows that BRL 34915 has both arrhythmogenic and antiarrhythmic effects. A detailed electrophysiological analysis has shown that drug infusion act on normal cardiac cells by decreasing the relative and absolute refractory period. BRL 34915 action is simulated by a decrease in the refractory period showing that the time frequency of the reentrant activity is increased and that the spatial size where the reentry is developing is becoming smaller. These two effects are arrhythmogenic, the simulated data being so in good agreement with the experimental ones. PMID- 1462735 TI - Analytical modeling of the hysteresis phenomenon in guinea pig ventricular myocytes. AB - In the present study, we have demonstrated hysteresis phenomena in the excitability of single, enzymatically dissociated guinea pig ventricular myocytes. Membrane potentials were recorded with patch pipettes in the whole-cell current clamp configuration. Repetitive stimulation with depolarizing current pulses of constant cycle length and duration but varying strength led to predictable excitation (1:1) and non-excitation (1:0) patterns depending on current strength. In addition, transition between patterns depended on the direction of current intensity change and stable hysteresis loops were obtained in stimulus:response pattern vs. current intensity plots in 14 cells. Increase of pulse duration and decrease of stimulation rate contributed to a reduction in hysteresis loop areas. Changes in amplitude and shape of the subthreshold responses during the transitions from one stable pattern to the other, suggested that activity led to an increase in membrane resistance, particularly in the voltage domain between resting potential, and threshold. Therefore, we modelled the dynamic behaviour of the single cells as a function of diastolic membrane resistance, using previously published analytical solutions. Numerical iteration of the analytical model equations closely reproduced the experimental hysteresis loops in both qualitative and quantitative ways. In particular, the effect of stimulation frequency on the model was similar to the experimental findings. The overall study suggests that the excitability pattern of guinea pig ventricular myocytes accounts for hysteresis and bistabilities when current intensity is allowed to fluctuate around threshold levels. PMID- 1462736 TI - Modifiable automata self-modifying automata. AB - One of the most important features of living beings that seems universal is perhaps their ability to be modified in a functional way. In order to modelize this characteristic, we designed automata with a finite number of instantaneous internal descriptions, with input(s) and output(s) and which are able to be functionally modified. The rules which govern the evolution of these automata (and the initial conditions) are randomly chosen at the beginning and once and for all. When such an automaton is linked by its input and output to a deterministic process, it always stabilizes and it then has the property to rebuild itself. Thus it made a function which is inverse of the external function. We demonstrate the prevalence of p = 1 length period and of tau = 0 transient length for automata with m instantaneous internal descriptions. PMID- 1462737 TI - Automatic search for model to simulate the differentiation of T lymphocytes within the thymus. AB - The differentiation of T Lymphocytes within the thymus is an important biological phenomenon during which these cell acquire their functions to further control the immune system. Numerous experiments under various conditions have been devised to understand the different mechanisms involved in this complex process. Nevertheless, interpretation of these experiments lead to still contradictory debatable hypotheses. Modelisation of this process through classical simulation methods cannot be envisaged because they are not adapted to modifications of the model structure, which is the point of interest. For these reasons, we proposed a new approach of automatic search for model. The program consists of four independent connected modules: The generator produces model, based on the rationale of formal grammars. Protocol and experimental data are stored in a set of experiments. The simulator using a protocol and a model provides simulated results. Finally, the supervisor by comparing simulated results and experimental data, adapts the model parameters to increase their fit and either chooses a new experiment to explore, or modifies the model structure. Change of the model structure is performed among still unexplored models according to their "promise" level, which is iteratively evaluated relatively to previously explored models through a proposed model distance. The generator is written in Prolog and the other modules in C++. The architecture of the program allows us to modify or complete a module without changing anything in the other modules. As a consequence, the proposed modeling approach conceived to study T lymphocyte differentiation within the thymus remains independent of this biological phenomenon and can be applied to other biological problems. PMID- 1462738 TI - [The Catastrophe theory and membrane physiological functions]. AB - This communication is based on a preliminary work which emphasized a topological model of biomembranes from Thom's Catastrophe Theory. In this model called swallowtail bifurcation set, the structural state of a biomembrane was within the control of two structural attractors. Then, the physiological act of this biomembrane resulted in a sudden transfer of weight from the hydrophilic attractor to the hydrophobic attractor. In this consecutive work, the physiological act appears to be one of the four stages which permit to describe the larger notion of cyclic membrane function. Two of these stages unfold in the structural axis of the swallowtail model. They prepare the two others (physiological act and refractory stages) which expand in the functional direction. This conceiving of cyclic membrane function is applied to physiological examples such as the action potential and the endocytosis. Then, changes in this function are discussed on the basis of pathological data. PMID- 1462739 TI - [Spermatocyte and ovum symbiosis, origin of ontogenesis and phylogenesis of metazoans]. AB - The origin of metazoa implies the passage from an eukarote protozoan to a protozygote ancestor of a metazoan zygote. The most probable hypothesis is that of a symbiotic origin of the first zygote by association of two protists one signifying a spherical oocell and the other a flagellated spermatozoan; this could be the first step of the metazoan ontogenesis and therefore also of the phylogenesis. The genesis can also be explained by two haploid genomes NX NY, three gametes (two spermatozoa and one ovule), NX apparently being able to create both forms, and two zygotes. A double symbiosis, a chromosomic crossing-over and a selective expulsion can prove it. PMID- 1462740 TI - [Quasicrystal organization in extracellular matrixes]. AB - In this note we argue that the theoretical approach, developed in the field of quasicrystals, may prove to be useful in a completely different area, namely biology, and more precisely for the transmission electron microscopy observation of biological structures this sections. Whatever the real three-dimensional structure is periodic, a generic cut will produce a quasiperiodic pattern. This is illustrated in a "theoretical" example inspired by the 3D organization of annelid cuticle. In addition, we discuss recent results on dislocations in quasicrystals, and their possible consequence about observation in biology. Finally, this analysis could be extended to images obtained from other technics, like freeze-fracture, and other materials, provided that certain length scale relations be satisfied. PMID- 1462741 TI - Modelling of in vivo calcium metabolism. I. Optimal cooperation between constant and rhythmic behaviours. AB - The relevance of nonlinear dynamics to calcium metabolism led us to reevaluate the role of Ca-regulating hormones in Ca homeostasis. We suggest that, firstly, the main Ca metabolic functions in rat-bone and gut--are organized as dynamic entities able to generate various temporal expressions, including self oscillating patterns and, secondly, Ca homeostasis results from interaction between both metabolic and hormonal oscillators. Following this schema, a major role for the hormonal system, with its circadian pattern, could be to act directly on metabolic functions or indirectly through feeding behaviour, in order to optimize, coordinate and synchronize the Ca fluxes at ECF level. PMID- 1462742 TI - Teflon/polyurethane arthroplasty of the knee: the first 2 years preliminary clinical experience in a new concept of artificial resurfacing of full thickness cartilage lesions of the knee. AB - Thirty-seven full-thickness knee cartilage lesions were treated with a Teflon/polyurethane composite implant in 23 patients. The preoperative diagnoses were osteoarthritis, osteonecrosis and a traumatic osteochondral lesion. The implant was fixed to the subchondral bone with Tissucol (Immuno, Vienna), a human fibrin glue. The leg was immobilized for 6 weeks followed by 8 days of continuous passive motion in parallel with full weight-bearing. High tibial osteotomy to correct a varus or valgus deformity was performed on 16 patients approximately 6 weeks after implantation of the composite implant. Fourteen patients were arthroscoped after 1 year, which demonstrated good fixation and congruity of the implant with the adjacent cartilage. All 23 patients were available for clinical and radiographic follow-up at a minimum period of 2 years after implantation. Seventy-eight percent of the patients reported complete pain relief. Eleven patients were rated as good, 3 as fair, 4 as poor, while 4 were loosenings. All loosenings were from knees with unicompartmental bipolar implantations and required only arthroscopic removal. Moreover, 21% of the patients had reduced range of motion post-operatively. No clinical synovitis was seen. This high incidence of stiff knees may be reduced by shortening or altogether eliminating the post-operative immobilization period in conjunction with early application of CPM. We conclude that a Teflon/polyurethane composite implant has been successful as a prosthetic knee resurface implant and demonstrates good biocompatibility. However, the use of unicompartmental bipolar implants should be avoided. PMID- 1462743 TI - [Classification of post-traumatic soft tissue lesions]. AB - A successful treatment of fractures with soft tissue injuries depends on surgical principles and on the individual prognosis of each trauma. Classification systems are ment to be an aid in taking therapeutical decisions in the assessment of the prognosis and in comparising of different lesions. In the anglo-american literature the classification of Gustilo in open fractures grade 1 to 3 and the subclassification of grade 3 lesions in A, B and C are the most accepted. In the german-spoken countries the classification of Tscherne and Oestern, dividing open and closed fractures in 4 different categories is the most used. PMID- 1462744 TI - [Functional sequelae in tibial shaft fractures with compartment syndrome following primary treatment with urgent fasciotomy]. AB - In a retrospective study on 28 patients, the incidence, nature and severity of the sequelae after severe lower leg trauma were studied. All patients had a tibial shaft fracture with a complete or impending compartment syndrome, treated with an urgent stabilisation and an adequate decompressive fasciotomy. In a thorough clinical examination, performed 17 months after trauma, the mobility of the knee and ankle joint, the perimetry of the lower leg and foot, and the muscle strength of all lower leg muscles were measured. Contractures were noticed, superficial sensibility was tested and an evaluation of march was done. More than one fourth of the patients showed late functional disabilities, mainly because of limitation of the dorsiflexion of the ankle joint, reduction of the muscle strength of the foot extensors, contractures of the foot flexors and abnormal superficial sensibility. The more severe the primary soft tissue trauma was, the more severe the functional disabilities were. The severity of the soft tissue damage, resulting from the trauma itself, is the most important factor for the late functional result after lower leg trauma. The compartment syndrome is certainly an aggravating factor when it is not treated by urgent fasciotomy. But this does not mean that all patients with lower leg fracture and compartment syndrome, treated with urgent fasciotomy, will show excellent functional end results. PMID- 1462745 TI - [Prevention of bacterial infection using selective intestinal decontamination in patients with cirrhosis admitted to intensive care. Controlled study in 120 patients]. AB - All cirrhotic patients admitted on a medical intensive care unit, were included in a randomized trial of selective intestinal decontamination provided there was no infection on admission. The selective intestinal decontamination consisted of a regimen of 3 oral, nonabsorbable antibiotics for the 74 first patients (Neomycin 1 gr, Colistin 1.500.000 U, Nystatin 1.000.000 U, every 6 hours), then of norfloxacin, 400 mg BID for the following patients. The duration of treatment was at least 5 days. Of the 120 patients, initially randomized to receive or not the treatment, 26 were ultimately excluded, mainly (18 cases) because of infection present but unrecognized at the time of admission. Ninety four patients were thus compared for the efficiency of the treatment, 45 in the treated group and 49 in the not treated group. The results showed a significant reduction of the episodes of septicemia in the treated group (4 versus 12, P = 0.044). This reduction was evident only for septicemia due to gram negative germs. Mortality was unaffected. When the risk factors were studied, bacterial infection was linked to the degree of hepatic failure. We recommend selective intestinal decontamination for cirrhotic patients admitted on intensive care unit, particularly when hepatic function is poor. PMID- 1462747 TI - Combined treatment of liver failure and hepatorenal syndrome with orthotopic liver transplantation. AB - Hepatorenal syndrome (HRS) is a severe complication of liver failure with high mortality. The pathogenesis of this reversible functional renal failure is not yet clearly understood. Diagnosis is based upon the association of clinical and biological criteria. A patient was admitted to our institution for severe liver failure secondary to an exacerbation of cirrhosis, where he developed a fulminant hepatorenal syndrome. Both, the renal and hepatic failure were successfully treated by orthotopic liver transplantation. Special attention was paid to the immunosuppressive treatment with Cyclosporine whose use, we believe, should be delayed until function has partially recovered. PMID- 1462746 TI - [Tolerance of adjuvant treatment combining postoperative intraportal chemotherapy and a systemic treatment based on 5-fluorouracil in colorectal carcinoma with a histologically poor prognosis]. AB - From April 89 to October 90, 41 patients operated for a Dukes B or C colorectal cancer were randomized to receive 6 courses of adjuvant treatment with (A) 5-FU alone (440 mg/m2 IV bolus 5/21 days) or (B) folinic acid (200 mg/m2 IV bolus 5/21 days) preceding 5-FU (370 mg/m2 in short infusion 5/21 days). Ten patients received also one course of immediate post-operative continuous portal infusion (5-FU 500 mg/m2/day x 7 followed by a 2 hours infusion of mitomycin C 10 mg/m2). The portal treatment was well tolerated (1 case of GI tract disturbances, 1 catheter obstruction). The toxicity of adjuvant systemic treatment was evaluated on 232 courses (125 A, 107 B). Hematologic and skin toxicities, alopecia and nausea-vomiting were mild. The limiting toxicities (expressed as percentages of courses) were stomatitis (grades 2-3: 11.4% A; 22.6% B) and diarrhea (grades 3-4: 7.3% A; 14.2% B; one toxic death was to deplore in arm B from a grade 4 diarrhea). The pilot study has demonstrated the feasibility of the adjuvant treatment proposed; a multicentric randomized trial (expected accrual: 800 patients) has therefore been activated on 11.01.90; all patients will also receive levamisole while radio-therapy will be mandatory for rectal cancer. PMID- 1462748 TI - [Acute hepatitis and poisoning by Amanita phalloides]. AB - We report the case of a 69-year-old woman who presented acute hepatitis due to Amanita Phalloides poisoning complicated of acute renal failure. Her clinical evolution was favorable under medical treatment whose actual modalities are discussed. PMID- 1462749 TI - Hepatobiliary cystadenoma with mesenchymal stroma: presentation of one case and review of the literature. AB - We present one case of hepatobiliary cystadenoma with mesenchymal stroma (CMS) which is a very unusual tumor of the biliary tract. These rare neoplasms have been identified as a distinct clinicopathological entity. They occur exclusively in middle-aged women with an average age of 45 years, and are located on the right hepatic lobe. Histologically, CMS are characterized by the presence of a typical dense stroma between an inner epithelial lining and an outer loose connective layer. Malignant transformation may occur and therefore a complete surgical resection of these premalignant neoplasms is indispensable. PMID- 1462750 TI - [Critical study of digestive tract dysplasia]. AB - Dysplasia designate the presence in a tissue of atypical architectural and cytological features similar to those observed in carcinogenesis. It must be clearly distinguished from metaplasia which is, in itself, a benign state characterized by the progressive replacement of a normal tissue by an other, normally foreign to this organ. Although the theoretical definition of dysplasia and its relation to carcinogenesis is well demonstrated, numerous difficulties remain regarding its classification and clinical applications. Recent research based on follow-up studies and on diagnostic reproducibility have somewhat clarified the problem, leading to a simplification of the classification in two tiers (high and low grade). High grade dysplasia can be considered as a high cancer risk necessitating a follow-up at short intervals and possibly requiring surgery. Low grade dysplasia, which can regress or progress very slowly represents a low cancer risk. After a first control at one or two months, it is suggested that endoscopic follow-up can be proposed at larger intervals (one or two years). The authors study the aspects of the dysplasia at the different levels of the gastrointestinal tract and summarise the clinical implication of this diagnosis. PMID- 1462751 TI - [Celiac disease: diagnostic criteria and motivation for request for intervention. Viewpoint of the Belgian Group of Pediatric Gastroenterology and Nutrition]. PMID- 1462752 TI - Blood-brain barrier and cerebrospinal fluid circulation. AB - There are two distinctive regions in the central nervous system of all vertebrates: the common brain region possessing the blood-brain barrier, and a group of several brain regions (circumventricular organs (CVOs) including the choroid plexus) devoid of the blood-brain barrier. Of the first, the morphological basis in vertebrates higher than teleosts is the brain-type capillary endothelium, and in elasmobranchs the perivascular astrocytic end-feet sealed by tight junctions. Of the second, the morphological basis is the fenestrated capillary with perivascular space. The pial connective tissue directly continues to the propria of circumventricular organs, and thus offers sites of cerebrospinal fluid drainage through CVO venous capillaries of which the fenestrated endothelia are anchored to perivascular tissues by the microfibrils of elastic fibers. The arachnoid granulations, which increase in size and number in accordance with the increasing volume of the skull are safety balloons against a sudden rise in intracranial pressure. They are possibly also sites of immune responses. PMID- 1462753 TI - [A study on the communication between the pectoral nerve and the extramural nerve branches of the intercostal nerves]. AB - Kumaki et al. (1979) defined the extramural nerve as the rudimentary sensory nerve which appeared on the upper thoracic wall; it branched off the root of the lateral cutaneous nerve of the second, third or fourth intercostal nerve, ran inferomedially adhering to the fascia of the intercostalis externus muscle and ended supplying the membrane covering the adjacent rib. They also stated that the extramural nerve (Rxm) occasionally became a cutaneous nerve which pierced the pectoralis muscles and supplied the skin covering the thoracic wall similar to the lateral cutaneous nerve (Rcl) or the anterior cutaneous nerve (Rca). Further, they proposed that the muscular nerves to the obliquus externus abdominis muscle which are usually situated below the fifth rib might be considered a part of this Rxm series. Although the definition of Rxm is still not widely accepted, Rxm is thought to be a key morphological factor influencing the variations of peripheral nerve arrangement on the thoracic wall. In the student course of gross anatomy dissection at Iwate Medical University School of Medicine during the years 1987 1991, three cases of Rxm communicating with the pectoral nerve and supplying the pectoralis major muscle were observed. Some cases have been reported in which Rcl innervates part of the pectoral muscles. However, the communication between the pectoral nerve and Rxm has not yet been discussed. Therefore, to clarify the morphological significance of the communication between Rxm and the pectoral nerve, the branching pattern and the distribution of the pectoral nerves were extensively investigated and the intramuscular nerve supply of some pectoral nerves, especially the pectoral nerves which communicated with Rxm, was examined in detail under a stereomicroscope. The results are summarized as follows: 1. In the first case, Rxm of the second intercostal nerve originated from Rcl, ran inferomedially adhering to the fascia of the intercostalis externus muscle and pierced the origin of the pectoralis minor muscle at the third intercostal space. Then Rxm turned superolaterally to communicate with a pectoral nerve which originated from the loop composed of the lateral and medial pectoral nerves and passed inferior to the pectoralis minor muscle. After communication, the pectoral nerve with Rxm supplied the caudalmost part of the sternocostal portion of the pectoralis major muscle. In the second case, a similar branch of Rxm of the second intercostal nerve passed inferior to the pectoralis minor muscle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1462754 TI - Epicardial formation in staged human embryos. AB - The manner of epicardial formation has been unequivocally clarified by electron microscopy in representative species of the vertebrates. In human embryology, however, information on the epicardial formation is still lacking. To fill the gap of knowledge, we performed the light microscopic observations on serial paraffin sections of human embryos at Carnegie stages 12 to 17. At stage 12, initial formation of the epicardium was seen in 2 of 6 embryos. As was seen in chick embryos, villous protrusions of the mesothelial cells extending from the sinus wall region touched the ventricle on the dorsal side to spread out on it as a simple squamous epithelium. At subsequent stages, the epicardial covering was extended concomitantly with histogenesis and organogenesis of the embryonic heart. Although the final stage was difficult to define at the light microscopic level, the epicardium was considered to cover the entire heart by late stage 16, on the basis of reference to the findings on chick embryonic heart. PMID- 1462755 TI - [Peptidergic innervation in the sinus hair follicles of several mammalian species]. AB - In this study, the detailed distribution of peptidergic nerve fibers in the sinus hair follicle was immunohistochemically investigated by the avidin biotin-complex method using antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in the cat, dog, hamster, rat, mouse and guinea pig. The peptide-immunoreactive (IR) nerve fibers presented a fine varicose appearance. They entered the sinus hair follicle after penetrating the capsule (Cap) at various levels. Peptide-IR fibers in the sinus hair were classified into the 3 types described below based on their course of entry and terminal distribution. Type A: these fibers arrive at the orifice of the sinus hair follicle from superficial dermis and innervate the upper portion of the follicle. Most of them form a network around the vibrissal shaft (VS) in the outer and inner conical body (OCB and ICB, respectively), and some are distributed around the rete ridge collar (RRC) and the sebaceous gland (SG). Type B: these fibers enter the lower third of the sinus hair follicle after forming a nerve bundle together with myelinated fibers, or accompany an artery. After distribution in the trabeculae (Trab) of the cavernous sinus (CS), they form a dense plexus in the connective tissue follicle (CTF) at the level of the CS. Some ascend through the CTF and terminate at the level of the ring sinus (RS). Type C: these fibers enter the sinus hair follicle at its base. They innervate the hair papilla (HP) and the CTF of the hair bulb. CGRP and SP were detected in all types of nerve fibers in all species investigated. These peptidergic nerve fibers showed the same distribution pattern, but CGRP fibers were more numerous than SP fibers. They were distributed at high density in the OCB, ICB, CTF, ringwulst (Rw), the Trab of the CS and the HP. A moderate number of VIP- and NPY-IR fibers, mainly types B and C, were detected in these portions in the cat, dog and hamster, but few fibers were observed in other portions or in other species. Although the basic structures of the sinus hair follicle presented almost the same features as in the mammalian species, the connective tissue of the HP extended to the level of the RS in the cat, rat, hamster, and guinea pig. In these species, CGRP-, SP- and/or VIP-IR fibers extended to the top of the papillary connective tissue, and in the cat, were especially well developed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1462756 TI - Relationship between the recurrent laryngeal nerve and the inferior thyroid artery in Japanese. AB - The anatomical relationship between the recurrent laryngeal nerve and the inferior thyroid artery was studied on 784 sides of the necks of 309 male and 123 female Japanese cadavers. On the right side, the nerve passed anterior to the artery in 32.4%, posterior to it in 26.7%, and between the branches of the artery in 40.9%. On the left side, the nerve was found coursing anterior to the artery in 4.9%, posterior to it in 65.8%, and between the branches in 29.3%. There was a statistically significant difference in the percentage distribution of the three types between the right and left sides, while no significant difference existed between males and females. The side difference in the relationship could be attributed to the difference in the course of the recurrent laryngeal nerve between the two sides. The collaterally symmetric cases of the relationship between the nerve and the artery were found more frequently in males (40.0%) than in females (28.6%). The present study revealed that the relationship between the nerve and the artery in Japanese was essentially similar to those in Americans and Europeans reported in other previous studies. PMID- 1462757 TI - [Nerve growth factor receptor (NGFR)-like immunoreactivity in the perineurial cells of the adult rat peripheral nerves: normal appearance and response to nerve section]. AB - The expression of the nerve growth factor receptor (NGFR)-like immunoreactivity in the perineurial cells of normal rat sensory and sympathetic nerves and after surgical severance was analyzed using a specific anti-rat NGFR monoclonal antibody (192-IgG). The perineurial cells as well as axonal endings showed NGFR like immunoreactivity in the terminal region of normal nerves and the immunoreactivity in the terminal perineurial cells was enhanced after nerve severance. In the nerve trunk region, no cellular elements exhibited NGFR-like immunoreactivity in normal rats, but immunoreactivity was induced in the innermost perineurial cells and all Schwann cells in portions distal to the severance. These findings suggest that the perineurial cells function to provide NGF for intact and regenerating axons by binding NGF to NGFR on the perineurial cell surface. PMID- 1462758 TI - Bilateral anatomical anomaly of anterior bellies of digastric muscles. AB - During the gross anatomy dissection of the submandibular region, both anterior bellies of the digastric muscles, especially the left one, were found to be enlarged. They were arranged as two parallel asymmetric bands extending from the hyoid bone to the chin. The posterior bellies of the digastric muscles were normal. The suprahyoid muscles showed no abnormalities. This anomaly represents an anatomical variation in the mylohyoid digastric muscle group in the floor of the mouth. PMID- 1462759 TI - A Taiwanese with a pair of sternalis muscles. AB - A pair of sternalis muscles have been found on both sides of the chest in an adult Taiwanese male. The muscles are located superficial to the medial part of the pectoralis major, arising from the sternum and are inserted into the sheaths of the rectus abdominis. They are innervated by the intercostal nerve. It should be emphasized that the sternalis muscle is rarely found in Taiwan. PMID- 1462760 TI - Clarke's column in sporadic amyotrophic lateral sclerosis. AB - Histological, ultrastructural and morphometrical observations on Clarke's column were carried out in 18 patients with sporadic amyotrophic lateral sclerosis (ALS) and 15 age-matched control subjects. Of the 18 ALS patients 6 had been on a respirator before death. Bunina bodies were found in the neuronal cytoplasm in 7 of the 12 non-respirator-supported ALS patients and in 3 of the 6 respirator supported patients. The number of spheroids was significantly higher in the non respirator-supported patients (P < 0.01) than in the control subjects; however, the number in the respirator-supported patients was about equal to that in the controls. The number of neurons in Clarke's column in the non-respirator supported ALS patients was not reduced, but in the respirator-supported patients they tended to disappear with time after respiratory support. These findings suggest that Clarke's column neurons are also involved primarily in the disease process in sporadic ALS. However, they may begin to disappear only after the patients require respiratory support. PMID- 1462761 TI - Vascular changes in the spinal cord in N-methyl-D-aspartate-induced excitotoxicity: morphological and permeability studies. AB - Our previous studies have demonstrated toxicity in spinal cord neuronal systems of middle-aged rats with continuous intrathecal infusion of N-methyl-D-aspartate (NMDA). The present study was undertaken to determine when during the course of excitotoxicity vascular changes occur. The model used was intrathecal infusion of NMDA in the region of the lumbar enlargement of the spinal cord. Horseradish peroxidase (HRP) was used as a marker of vascular permeability alterations occurring in this model. Pathological changes were observed in the cord gray matter of all rats infused with 30-60 micrograms/min NMDA for 30 or 60 min. The changes consisted of swelling of dendrites which gave the neuropil a vacuolated appearance. There was expansion of the extracellular spaces in these areas and neurons were shrunken with pyknotic nuclei. These changes were more frequently encountered in the posterior than anterior horns and were specific for NMDA since they did not occur in NMDA-infused rats pretreated with MK-801, a specific NMDA antagonist. Endothelial dysfunction manifested as increased permeability to HRP. This was a consistent finding in all rats infused with the higher dose of NMDA and was less frequent in those infused with 30 micrograms/min and no vascular changes were observed in rats infused with NMDA for 30 min despite the presence of tissue changes. Increased permeability affected all types of vessels but principally, capillaries and venules. There was no evidence of endothelial necrosis or vascular occlusion. This study demonstrates that in excitotoxin mediated tissue damage, breakdown of the blood-brain barrier follows the development of nervous tissue damage. Thus, edema is not a significant feature of early lesions in excitotoxin-induced brain injury. PMID- 1462762 TI - Allocortical neurofibrillary changes in progressive supranuclear palsy. AB - Silver techniques for intraneuronal cytoskeleton abnormalities (neurofibrillary tangles and neuropil threads) and extracellular A4-amyloid deposits were used to examine lesions of the cerebral cortex in six cases of progressive supranuclear palsy (three were mentally unimpaired and three showed moderate degrees of dementia). Deposits of A4-amyloid protein occurred in small numbers or were absent. Neurofibrillary tangles and neuropil threads were present in all cases and were largely confined to the allocortex. A characteristic pattern of changes was found in the entorhinal cortex. The three mentally unimpaired individuals had mild cortical changes virtually confined to the transentorhinal region while all of the demented patients showed severe destruction of the superficial cellular layer in both the transentorhinal and entorhinal region. This pattern of allocortical destruction closely resembles that seen in clinically incipient Alzheimer's disease or in mentally impaired cases of Parkinson's disease. The entorhinal region receives dense input from isocortical association areas and projects via the perforant path to the hippocampal formation. The cells of origin of major portions of the perforant path are located within the superficial entorhinal cellular layer. Destruction of this layer partially or totally disconnects the hippocampus from the isocortex. The specific pattern of entorhinal destruction is considered to contribute to cognitive impairment and personality changes, frequently seen in patients with progressive supranuclear palsy. PMID- 1462763 TI - Immunotactoid-like endoneurial deposits in a patient with monoclonal gammopathy of undetermined significance and neuropathy. AB - An 85-year-old man with a 2-year history of progressive lower limb weakness and paresthesia was found to have an IgG kappa monoclonal gammopathy of undetermined significance (mgus). Clinical and electrophysiological studies revealed a severe distal bilateral symmetrical polyneuropathy. A sural nerve biopsy showed extensive nerve fibre loss with the deposition of large amounts of amorphous material throughout the endoneurium. Electron microscopy showed the deposits to be composed of microtubular structures which were located diffusely throughout the endoneurium. The deposits were also located within the lumina of the vasa nervorum, some of which were undergoing disintegration and rupture with release of the proteinaceous material into the endoneurium. The regions of the nerve in which they appeared most numerous showed more severe nerve fibre damage than other areas. These microtubular structures were also observed in disintegrating vessels and adjacent endoneurium. On immunohistochemistry they stained with antibody to IgG. Identical deposits were found in the dermis in which there was a leucocytoclastic vasculitis. Located in linear arrays within the axons of myelinated and unmyelinated fibres were highly organised tubular structures resembling immunotactoids. Identification of immunotactoid-like structures within the nerve is unique and may be another mechanism by which monoclonal proteins can induce nerve fibre injury. PMID- 1462764 TI - Moderate hypothermia reduces blood-brain barrier disruption following traumatic brain injury in the rat. AB - The effects of moderate hypothermia on blood-brain barrier (BBB) permeability and the acute hypertensive response after moderate traumatic brain injury (TBI) in rats were examined. TBI produced increased vascular permeability to endogenous serum albumin (IgG) in normothermic rats (37.5 degrees C) throughout the dorsal cortical gray and white matter as well as in the underlying hippocampi as visualized by immunocytochemical techniques. Vascular permeability was greatly reduced in hypothermic rats cooled to 30 degrees C (brain temperature) prior to injury. In hypothermic rats, albumin immunoreactivity was confined to the gray white interface between cortex and hippocampi with no involvement of the overlying cortices and greatly reduced involvement of the underlying hippocampi. The acute hypertensive response in normothermic rats peaked at 10 s after TBI (187.3 mm Hg) and returned to baseline within 50 s. In contrast, the peak acute hypertensive response was significantly (P < 0.05) reduced in hypothermic rats (154.8 mm Hg, 10 s after TBI) and returned to baseline at 30 s after injury. These results demonstrate that moderate hypothermia greatly reduces endogenous vascular protein-tracer passage into and perhaps through the brain. This reduction may, in part, be related to hypothermia-induced modulation of the systemic blood pressure response to TBI. PMID- 1462765 TI - The distribution of Challenge virus standard rabies virus versus skunk street rabies virus in the brains of experimentally infected rabid skunks. AB - The proposal that the bizarre behavioral changes which occur during rabies infection are due to selective infection of limbic system neurons was further studied in skunks (a species important in naturally occurring disease). A detailed immunohistochemical study of brains of skunks experimentally infected with either Challenge virus standard (CVS) or street rabies virus revealed only trace amounts of viral antigen in many limbic system neurons and marked differences in viral distribution between street and CVS virus. These data were collected during early stage rabies when behavioral changes occur. Areas which contained heavy accumulations of street rabies virus but low amounts of CVS rabies virus were the neuronal perikarya and processes of the dorsal motor nucleus of the vagus, midbrain raphe, hypoglossal and red nuclei. In contrast, large accumulations of CVS virus were found in the Purkinje cells of the cerebellum, the habenular nuclei and in pyramidal cells throughout the cerebral cortex, while corresponding areas in all street virus-infected skunks contained minimal antigen. These findings were very consistent for animals of the same experimental group and between skunks inoculated both intramuscularly and intranasally with skunk street virus. Skunks inoculated intramuscularly with CVS rabies virus failed to develop rabies. Since, in this model, street virus infection generally produces furious rabies and CVS infection results in dumb rabies, we speculate that the behavioral changes which occur in these two different clinical syndromes are due to the heavy and specific accumulation of virus in different regions of the CNS. These results show that regions other than those of the limbic system may also be involved in the pathogenesis of behavior changes in rabid animals. PMID- 1462766 TI - Ki-M1P as a marker for microglia and brain macrophages in routinely processed human tissues. AB - The monoclonal antibody Ki-M1P recognizes a formalin/paraffin-resistant differentiation epitope of monocytes and their macrophage derivatives [Radzun et al., Lab Invest 65:306, 1991]. To evaluate its usefulness for neuropathology, we examined a variety of routinely processed tissues using immunohistochemistry. In normal brains, positivity was restricted to ramified microglial cells. Intense labeling of macrophages, ramified and ameboid microglial cells, and rod cells was seen in brains with various degenerative and inflammatory disorders. Astrocytes were negative as determined by double-immunofluorescence labeling using Ki-M1P and anti-glial fibrillary acidic protein (GFAP). Histiocytic lesions (histiocytosis X, xanthogranulomas, granulomatous inflammation) were immunopositive. Among 107 tumors, reactivity of Ki-M1P was observed with some schwannoma and meningioma tumor cells. In addition to macrophages, most gliomas contained small, elongated Ki-M1P-positive cells, which were negative for GFAP. Positivity was also found in two glioblastoma cell lines. Immunoblotting performed on spleen, meningioma and glioblastoma specimens revealed one to three bands in the range of 110 to 130 kDa. We conclude that Ki-M1P can serve as a reliable marker for brain macrophages and microglial cells in routinely processed normal and non-neoplastic tissues, whereas due to the unexpected immunoreactivities results obtained with neoplastic tissues should be carefully interpreted. PMID- 1462767 TI - Induction of FOS and JUN proteins after focal ischemia in the rat: differential effect of the N-methyl-D-aspartate receptor antagonist MK-801. AB - FOS and JUN proteins are transcription factors thought to be involved in coupling neuronal excitation to target gene expression. Cortical infarction of consistent size and location was produced by irradiating the rat brain with Xenon light through the intact skull for 20 min following systemic injection of the photo sensitizing dye, rose bengal. To investigate the time course and distribution pattern of five cellular immediate early gene (IEG)-encoded proteins after focal ischemia, the expression of c-FOS, FOS B, c-JUN, JUN B and JUN D was studied immunocytochemically in sham-operated control animals and at different postischemic time intervals up to 24 h. A separate group of animals was pretreated with the non-competitive N-methyl-D-aspartate (NMDA) antagonist MK 801. Photochemically induced focal ischemia caused a rapid induction of FOS and JUN proteins in the entire ipsilateral cortex apart from the ischemic focus. Immunoreactivity in the ipsilateral subcortical gray and white matter and in the entire contralateral hemisphere was indistinguishable from control animals. Individual IEG-encoded proteins were sequentially induced with increased levels of immunoreactivity persisting for different time periods up to 24 h. c-FOS, FOS B, c-JUN and JUN B exhibited a characteristic distribution pattern as reflected by different staining intensities in individual cortical layers. The rapid IEG induction in the entire ipsilateral sensorimotor and limbic structure-associated cortices after photochemically induced infarction most likely reflects spreading depression caused by ischemia and mediated by NMDA receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462768 TI - Ultrastructural features of spongiform encephalopathy transmitted to mice from three species of bovidae. AB - The ultrastructural neuropathology of mice experimentally inoculated with brain tissue of nyala (Tragelaphus angasi; subfamily Bovinae), or kudu (Tragelaphus strepsiceros; subfamily Bovinae) affected with spongiform encephalopathy was compared with that of mice inoculated with brain tissue from cows (Bos taurus; subfamily Bovinae) with bovine spongiform encephalopathy (BSE). As fresh brain tissue was not available for nyala or kudu, formalin-fixed tissues were used for transmission from these species. The effect of formalin fixation was compared with that of fresh brain in mice inoculated with fixed and unfixed brain tissue from cows with BSE. The nature and distribution of the pathological changes were similar irrespective of the source of inoculum or whether the inoculum was from fresh or previously fixed tissue. Vacuolation caused by loss of organelles and swelling was present in dendrites and axon terminals. Vacuoles were also seen as double-membrane-bound and single-membrane-bound structures within myelinated fibres, axon terminals and dendrites. Vacuoles are considered to have more than one morphogenesis but the structure of vacuoles in this study was nevertheless similar to previous descriptions of spongiform change in naturally occurring and experimental scrapie, Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and kuru. Other features of the ultrastructural pathology of the transmissible spongiform encephalopathies including dystrophic neurites and scrapie-associated particles or tubulovesicular bodies were also found in this study. Neuronal autophagy was a conspicuous finding. It is suggested that excess prion protein (PrP) accumulation, or accumulation of the scrapie-associated protease-resistant isoform of PrP, may lead to localised sequestration and phagocytosis of neuronal cytoplasm and ultimately to neuronal loss. PMID- 1462769 TI - Immunohistochemistry and proliferative activity in Lhermitte-Duclos disease. AB - We have evaluated a recurrence of Lhermitte-Duclos disease by immunohistochemistry for Purkinje cell markers and proliferative activity (proliferating cell nuclear antigen), by electron microscopy and for DNA ploidy (image analysis). While most of the abnormal neurons in the lesion appear to be derived from granule cells, several Purkinje cell specific polyclonal and monoclonal antibodies, including L7, PEP 19 and calbindin, labeled a minor subpopulation. Staining with monoclonal antibodies to proliferating cell nuclear antigen and measuring cell DNA index and ploidy with a cell image analyzer revealed no proliferative activity. Electron microscopy findings were similar to those previously reported. In spite of its recurrence, our findings support the notion that Lhermitte-Duclos disease is malformative, not neoplastic, and that the characteristic neurons are derived predominantly but not exclusively from a non-Purkinje cell source, probably the granule cell. PMID- 1462770 TI - Myelination of two axons by a single Schwann cell. AB - A Schwann cell can form only one internode of myelin around an axon. However, we observed the formation by a single Schwann cell of myelin around two axons of different diameters in the sural nerve of a 45-year-old man with mononeuritis multiplex. Schwann cell processes spiraled in the same direction around each axon, forming mesaxons. The findings in this case appear to be an undescribed type of aberrant myelination. PMID- 1462771 TI - Anaplastic large cell Ki-1 lymphoma in the central nervous system: report of an autopsy case. AB - A 45-year old immunocompetent man presented with multiple lesions in the brain. A histological examination of the tumors showed a diffuse infiltrate of lymphoid cells with cellular polymorphism and of multinucleated giant cells. These cells were immunolabeled with antibodies against B cell lineage and with a monoclonal antibody, Ber-H2 (CD30), which showed the presence of Ki-1 antigen. Recently, among systemic non-Hodgkin's lymphomas, attention has been given to Ki-1-positive lymphomas, which have been incorporated in the up-dated Kiel classification. We report here a case of Ki-1-positive lymphoma arising in the CNS and review previously reported cases. PMID- 1462772 TI - Measurement, analysis, and modelling of the caloric response. 2. Evaluation of mental alerting tasks for measurement of caloric-induced nystagmus. AB - Management of the patient's level of arousal is one of the most important variables in obtaining consistent and strong caloric responses. The patient may suppress the caloric response and/or exacerbate beat-to-beat variability if some type of mental alerting (MA) task is not used to focus the patient's attention from his or her dizziness. An experiment was undertaken to evaluate simple MA tasks in terms of associated caloric response strength and variability. Warm caloric responses were measured while each of 10 normal subjects performed eight different MA tasks. The mental exercises included two math tasks, two quizzing tasks, two hand-motor tasks, and two alphabet tasks. One of the tasks in each complementary pair required the subject to interact with the examiner throughout the caloric response. Minimal or no interaction was required for the companion task. The relative ordering among the eight MA tasks was compared in terms of total sum of ranks, summed across 15 performance measures taken from caloric response indices. The highest-ranked altering task was an exercise requiring subjects to name or list local cities, states in the U.S.A., colors, etc. The lowest-ranked tasks were backward counting exercises and reflexive quizzing, which are the traditional tasks used in the clinic. PMID- 1462773 TI - Measurement, analysis, and modelling of the caloric response. 1. A descriptive mathematical model of the caloric response over time. AB - A mathematical model for describing the caloric response over time offers many important advantages over the commercially-available qualitatively-fitted curves that are now used by the clinician for evaluating caloric results. In this report advances in the development of a nonlinear least-squares mathematical model are discussed and the roles and derivations of fitting parameters and curve-derived indices are outlined. This model provides a rigorous and objective description of the caloric response in its entirety with four continuous parameters. These fitting parameters make it possible to 1) describe individual caloric responses precisely and uniquely, 2) compare pairs of individual caloric responses or groups of caloric responses statistically, 3) extract information not previously available, 4) quantify variability within the caloric response, and 5) model physical properties of the caloric stimulus and physiological variables affecting the caloric response. Results from this model are compared with the results from our earlier models and with traditional multiparameter caloric results. PMID- 1462774 TI - Middle ear gases. AB - The ex vacuo theory, claiming that air enters the middle ear through the Eustachian tube and oxygen leaves it into the blood by diffusion, does not provide a complete explanation and description of the mechanism of middle ear aeration. This study shows that both the gas diffusion between the middle ear and the blood and the flow of gas through the Eustachian tube are bidirectional processes for all the gases concerned N2, CO2, O2 as well as H2O. PMID- 1462775 TI - Diagnostic value of tympanometry in otitis media with effusion. AB - Three particular applications of tympanometry are stressed. In the first place, tympanometric screening fails to give any appreciation of the tubal dysfunction evolution. During general anaesthesia, nitrogen oxide diffusion in the middle ear can hide effusion. Secondly, the correlation between tympanometric curves and middle ear effusion is far lower than usually assumed. PMID- 1462776 TI - [Otologic manifestations of Wegener's disease]. AB - Two cases of otologic involvement in Wegener's granulomatosis are reported. Symptoms are referable to those of an acute otitis media with impaired hearing. The ANCA test is helpful in the diagnosis. Immunosuppressive therapy in association with corticosteroids is the treatment of choice. PMID- 1462777 TI - [Etiology of deafness in children]. AB - A retrospective etiological study of 112 files of deaf children is presented. A prenatal etiology is found in 42.8%, a perinatal in 19.6% and a postnatal in 13.4% of the cases. No cause was suspected in 30.3% of the cases. These results emphasise existing literature. PMID- 1462778 TI - [Proposal for an original method of high-frequency audiometry using mathematical equations]. AB - Many studies have established high-frequency audiometry norms. Unfortunately the majority presents different averages for each decade, sex and frequency together with standard deviations. In order to solve these problems we established our norms on a widespread audiometer for each sex based on a strictly normal hearing sample. We calculated the linear regression between age and hearing loss for each frequency. We propose a set of equations to predict the "normal" threshold of a subject in function of age and sex. PMID- 1462779 TI - [Evoked oto-acoustic emissions: results in at-risk newborn infants]. AB - Fourty newborns (80 ears) from the intensive care unit were tested with evoked oto-acoustic emission (EOAE). The occurrence of EOAE was 93%. PMID- 1462780 TI - A hairy polyp of the middle ear and mastoid cavity. AB - A case of a 'hairy polyp', a dermoid tumor of the middle ear and the mastoid cavity is described, which is very unusual location. The radiological, surgical and histological features are discussed. Comment is made on the differentiation between dermoid cysts and teratomas and on the scarcity of both tumors in the area of the temporal bone. PMID- 1462781 TI - [Endonasal dacryocystorhinostomy (95 cases)]. AB - A series of 95 intranasal dacryocystorhinostomies for ophthalmologic problems were performed. The operative technique as well as the results are discussed. Success rate is about 95.8%, of which 82.1% with immediate results. Even if the results of both intranasal and external approaches are equivalent, the intranasal one presents a little advantage. No intraoperative complications are observed. PMID- 1462782 TI - [Problems with flute playing: an otological problem? Case report of a peculiar cerebellar astrocytoma]. AB - A rare case of cerebellar astrocytoma presenting as a cerebellopontine angle tumour is discussed. A 35-year old woman noticed a bizarre twitching and fatigability of the left upper lip while playing the flute. There was also a mild hearing loss on the left side and she sometimes felt unsure of herself when walking. A thorough examination by means of speech audiometry, electronystagmography, ABR, CT-scan and MRI revealed a large, partly calcified mass occupying the cerebellopontine angle. Only the histological examination of the surgical specimen revealed the true nature of the tumour. The special characteristics of this tumour and the unusual clinical course are discussed. The importance of a good histological diagnosis is stressed. PMID- 1462783 TI - [Place of the otorhinolaryngologist in the multidisciplinary approach to neurofibromatosis]. AB - Neurofibromatosis is one of the most common inherited human disorders. Two types have been recognized, NF 1 and NF 2. Clinical and genetic aspects of the disease clear the way to the aims and indications of the multidisciplinary approach of the neurofibromatosis patients and their families. To study the uniformity of patient management (protocol), a number of Belgian and Dutch medical centres were contacted. Great importance is attached to the common as well as the varying points of these protocols. We emphasize the part played by the ENT specialist in the multidisciplinary approach of neurofibromatosis type 1 and 2. PMID- 1462784 TI - Hemangiopericytoma of the head and neck: a report of four cases and a literature review. AB - Hemangiopericytoma is an infrequent vascular tumor that rarely appears in the head and neck. The nasal cavity and the paranasal sinuses are most often involved. Four cases are added to the literature and some important features are stressed. The clinical presentation is aspecific. Diagnosis is made only by careful histological examination with special stainings (reticulin, immunohistochemistry with Ulex Europaeus) and gives an idea about the grading. Treatment with radical surgery, if possible, is effective while preoperative embolisation can reduce the risk of hemorrhage. The median follow-up of the present cases is only 3 years. During this period no recurrence was observed. We suggest that more radical resections can probably reduce the local recurrence rate. However lifetime clinical follow-up is warranted since late recurrences have been reported in almost half of the patients. PMID- 1462785 TI - On the role of global and local visual information in goal-directed walking. AB - The aim of the present study was to determine what interactions occur between the visual information available to walking subjects in the global optical flow and those of a more local nature relating to the dilation rate of a target on the retina. A goal-directed walking task was used in which thirteen subjects were asked to stop spontaneously as near as possible to a stationary target. The experiment was carried out in a special room, by means of a texture flow generator with which the velocity and direction of the optical flow arising from the ground were varied. Twelve experimental conditions were tested, involving various combinations of target size and texture velocity. The results show that with both of the targets, modifications to the global flow significantly affected the subjects' performances (walking speed and time-to-contact with the target upon braking) in the fast-approaching texture situation, but not in the receding or slowly-approaching situations. The results are discussed as to what they reveal about the visual strategies used by an actively moving observer to anticipate a collision with a stationary target. PMID- 1462786 TI - Dynamic decision making: human control of complex systems. AB - This paper reviews research on dynamic decision making, i.e., decision making under conditions which require a series of decisions, where the decisions are not independent, where the state of the world changes, both autonomously and as a consequence of the decision maker's actions, and where the decisions have to be made in real time. It is difficult to find useful normative theories for these kinds of decisions, and research thus has to focus on descriptive issues. A general approach, based on control theory, is proposed as a means to organize research in the area. An experimental paradigm for the study of dynamic decision making, that of computer simulated microworlds, is discussed, and two approaches using this paradigm are described: the individual differences approach, typical of German work in the tradition of research on complex problem solving, and the experimental approach. In studies following the former approach, the behaviour of groups differing in performance is compared, either with respect to strategies or with respect to performance on psychological tests. The results show that there are wide interindividual differences in performance, but no stable correlations between performance in microworlds and scores on traditional psychological tests have been found. Experimental research studying the effects of system characteristics, such as complexity and feedback delays, on dynamic decision making has shown that decision performance in dynamic tasks is strongly affected by feedback delays and whether or not the decisions have side effects. Although neither approach has led to any well-developed theory of dynamic decision making so far, the results nevertheless indicate that we are now able to produce highly reliable experimental results in the laboratory, results that agree with those found in field studies of dynamic decision making. This shows that an important first step towards a better understanding of these phenomena has been taken. PMID- 1462787 TI - Benefits from attention depend on the target type in location-precued discrimination. AB - In previous research, we found that precuing of attention to a target location greatly improved discrimination of targets that differed in line arrangement, but had little effect on discrimination of targets that differed in line orientation. In the present research, a number of other targets that represent various feature differences were used. The new data are consistent with and extend our earlier findings by showing that (1) there is some effect of precuing with all targets tested, and (2) the size of precuing effects varies in a complex way with the nature of the target. Moreover, the difficulty of the discrimination cannot explain the size of the precuing effects. A framework for understanding the events occurring during trials in the location-cuing paradigm is presented and applied to these results. PMID- 1462788 TI - The role of vision in the temporal and spatial control of handwriting. AB - The general observation that handwriting is not noticeably impaired by the withdrawal of vision can be explained in two ways. One might argue that vision is not needed during the act of writing. Micro-analyses should then reveal that spatial as well as temporal writing features are identical in conditions of vision and no vision. Alternatively, it is possible that vision is needed during the act of writing, but that without vision possible errors and inaccuracies have to be prevented. Assuming that the latter would place an extra demand on movement control, this should be revealed by an increase in processing time. We have found evidence for the latter view in the present study in which 12 subjects wrote a nonsense letter sequence with and without vision. Close examination showed that writing shapes remained equally invariant under both vision conditions, suggesting that spatial control was unaffected by withdrawing vision. The prediction that invariance of shapes is preserved in the absence of vision at the expense of processing time increments was confirmed. The increase of reaction time observed when visual guidance was withdrawn suggests that more processing time was needed prior to the movement start. Moreover, the RT increment was larger when a short writing duration was instructed. The present findings will be discussed in light of the remarkable flexibility of writing as a motor skill in which writers appear to be able to employ specific strategies to preserve shape in the absence of visual guidance. PMID- 1462789 TI - Does evidence of inflammation on Papanicolaou smears of pregnant women predict preterm labor and delivery? AB - BACKGROUND: Preterm delivery is the most common cause of neonatal morbidity and mortality in the United States. There is evidence that cervicovaginal infection could predispose to preterm labor. This study explored a possible association of evidence of inflammation on an otherwise normal Papanicolaou smear obtained during pregnancy with subsequent preterm labor and preterm delivery. METHODS: Using a retrospective matched cohort design, we studied women who gave birth to live singleton infants at the University of Missouri Hospital and Clinics during a 21-month period. Papanicolaou smears were obtained from 1 to 8 months before delivery and were interpreted in the same cytopathology laboratory. Data pertaining to outcome variables and potential confounding variables were collected from hospital charts. RESULTS: Incidence rates were 14.4 percent for labor < 37 weeks' gestation (preterm labor), 12.3 percent for hospitalization for preterm labor, 9.9 percent for delivery < 37 weeks (preterm delivery), 2.6 percent for delivery < 34 weeks, and 7.5 percent for birth weight < 2500 g. On univariate and multivariate analyses, there were no significant differences in any outcome between the 293 women with inflammation and the 284 women without inflammation on Papanicolaou smear. Results were unchanged when the analysis was limited to the 412 women who received no antibiotics during pregnancy. Among the 38 women with a history of preterm labor or preterm delivery, those with cervical inflammation had a higher rate of preterm labor than those without inflammation. CONCLUSIONS: In the sample as a whole, there was little evidence that findings of inflammation on Papanicolaou smear constituted a risk factor for preterm labor or preterm delivery. The data suggest that inflammation could be associated with an increased risk in a subgroup of women at higher risk by virtue of their obstetric history. PMID- 1462791 TI - Survey and evaluation of newsletters marketed to family physicians. AB - BACKGROUND: Newsletters are marketed to physicians to provide a concise, accurate, and timely overview of the medical literature. The goal of these newsletters seems to be to present information that can be a suitable substitute for reading the original article. The purpose of this paper is to describe and evaluate newsletters pertinent to family physicians. METHODS: Newsletters appropriate for family physicians were selected by collecting newsletter advertisements and by searching newsletter directories. A 3-month sample and pertinent data were collected from the publishers. Evaluation criteria included accuracy and completeness of the abstracts, scope of coverage of the medical literature, and relevance of article sources. RESULTS: Eight newsletters were collected and evaluated. Accuracy was high for the evaluated abstracts. Abstract completeness averaged only 70 percent (range 55 percent to 92 percent). The type and source of abstracted articles varied widely among the newsletters. CONCLUSION: Newsletters available to family physicians vary widely; personal evaluation should supplement the results of the evaluation. PMID- 1462790 TI - Community attitudes and knowledge about advance care directives. AB - BACKGROUND: Patients and their physicians are increasingly being encouraged to discuss end-of-life decisions. The purpose of this study was to enhance understanding of the public's attitudes and knowledge about medical decision making and advance care directives. METHODS: Eight focus groups of community members discussed their understanding of and attitudes about advance care directives. Transcripts of these discussions were analyzed using coding categories created from the transcripts. RESULTS: Eighty-three people attended the focus groups. Most discussions of advance care directives involved family members in the setting of family or personal illness. Elderly persons commonly confused wills with living wills. Most who had given advance directives did so either to make others follow their wishes or to ease family burdens. Among the great variety of reasons for not using advance directives was a perceived lack of personal relevance, as well as conceptual, moral, and practical difficulties. Participants were divided about whether it was appropriate for physicians to initiate discussions about life-sustaining care with their patients. We discerned three themes affecting individuals' opinions about personal decision making about advance directives: (1) trust in family and the medical system, (2) need for control, and (3) knowledge about advance directives. CONCLUSIONS: Although living wills are advocated by many authorities, and many of our participants endorsed their use, our participants also cited numerous cautions and impediments to their use. As the role of advance care directives changes, physicians will need to be aware of their patients' perceptions, as well as the legalities of these documents. PMID- 1462792 TI - Teaching physicians to be patient: a hospital admission experience for family practice residents. AB - BACKGROUND: A program has been developed to sensitize physicians to the discomforts, uncertainties, and anxieties experienced by patients on admission to the hospital, so that greater empathy and increased communication can be fostered with their own hospitalized patients. METHODS: For the last 5 years, all incoming family medicine residents at Long Beach, California, Memorial Medical Center have been admitted incognito to the hospital during their first day in the residency. Hospitalized residents are assigned an admission diagnosis and an associated disability, given a pseudonym, and provided with fabricated insurance information (by the hospital administration) to facilitate their admission. Each incoming group of 6 residents is admitted over the course of an afternoon and evening and discharged the next morning. Residents evaluated the admission experience by means of before-and-after questionnaires. They and residency graduates also responded to a follow-up survey instrument that asked participants to assess the program's long-term educational impact (response rate, 100 percent; n = 30). RESULTS: Although the program is carried out annually, we have been able to admit the residents to this large (998 beds) medical center typically without their identities being discovered, resulting in a realistic educational experience. While diagnoses are contrived, the discomforts are real, and participants become acutely aware of the loneliness, pain (e.g., from intravenous lines), and uncertainty experienced by patients. Long-term effects on day-to-day practice attributed to the program by residents and graduates include minimizing orders for nonessential tests and middle-of-the-night examinations and keeping patients well-informed (especially letting them know when they will be seen by the physician). CONCLUSIONS: The effort, logistical problems, and costs associated with hospitalization of incoming residents disguised as patients appear to be offset by the admission program's long-term impact on participants' sensitivity regarding experiences undergone by hospitalized patients and their awareness of their role in helping to ameliorate discomforts associated with hospital admission. Strong support from the hospital administration, however, is essential to the success of this type of program. PMID- 1462793 TI - Chronic headaches in family practice. AB - BACKGROUND: More than 11 million people in the United States have moderate or severe migraine resulting in much suffering and millions of lost work days annually. Staying abreast of current advances in headache management is important for family physicians, who care for most headache patients. METHODS: MEDLINE files were searched from 1982 to the present using the key words "headache," "migraine," "serotonin," and "cerebral circulation." Also searched were the journals Headache and Cephalalgia and the published proceedings of meetings of the American Association for the Study of Headache, the International Headache Society, and the Migraine Trust. RESULTS AND CONCLUSIONS: A new headache classification based on clinical symptoms has been published by the International Headache Society, which clarifies headache diagnoses. Though headaches with serious underlying disease occur only rarely in family practice, physicians must be familiar with the clinical signs indicating the presence of such problems, and any change in or unusual presentation of headache warrants investigation. Headache research has expanded in the past decade, much of which has been directed at raising the standards of treatment. Pharmacologic treatment falls into two categories: acute or abortive treatment and preventive treatment. Analgesic overmedication by headache patients is commonplace and leads to withdrawal symptoms and the development of chronic daily headaches, for which effective treatments are now available at both ambulatory and inpatient levels. At the more basic research level, serotonin receptor studies have provided an impetus for revealing underlying headache mechanisms. A new serotonin agonist, sumatriptan, has proved effective in treating acute migraine and will no doubt be followed by further serotonergic drugs. Patient education, relaxation therapy, and other nonpharmacological approaches, as well as good overall standards of care, are essential ingredients in headache management. Family physicians are well-equipped to offer these approaches to their patients with headache. PMID- 1462794 TI - Premature labor, Part II: Management. AB - BACKGROUND: As the second paper in a two-part series on preterm labor, this article discusses the management of preterm labor as it relates to risk reduction, tocolytic therapy, corticosteroids, and antibiotics. METHODS: Published literature on the management of preterm labor was reviewed by searching MEDLINE files from 1983 to the present, using the terms "preterm labor," "premature labor," "preterm labor and antibiotics," "tocolytic agents," "tocolysis," "betamethasone," and "premature rupture of membranes." Additional references were obtained by cross-referencing bibliographies from available articles. RESULTS AND CONCLUSIONS: Effective management of preterm labor and birth begins with an assessment and reduction of risks for all pregnant women. In addition, pregnant women should be screened and appropriately treated for urologic and gynecologic infections (e.g., syphilis, gonorrhea, Chlamydia, and bacterial vaginosis). Women who are at high risk for preterm birth should be enrolled in a preterm birth prevention program that includes frequent contact with health professionals, patient education about the signs and symptoms of preterm labor, home monitoring, and regular cervical examinations. For women who develop preterm labor that does not require immediate delivery, recommended management strategies include reduced activity, early tocolytic therapy, corticosteroids for up to 34 weeks' gestation (both for women with intact and ruptured membranes), and antibiotics for known infections. Early studies also suggest that prophylactic antibiotics can be beneficial for women with idiopathic preterm labor or preterm premature rupture of membranes. PMID- 1462795 TI - Preemployment examinations: how useful? AB - BACKGROUND: An article in the March-April 1991 Journal of the American Board of Family Practice noted a lack of consensus among family physicians regarding preemployment testing of workers. Family physicians do not seem to adhere to any explicit or uniform criteria in performing these tests. Previous writers have suggested how these examinations might help both the employer and the worker. The Americans with Disabilities Act, which went into effect 26 July 1992, however, appears to make true preemployment examinations illegal. METHODS: A review of the Healthline (1975 to 1991) and the MEDLINE (1980 to 1991) data bases using the MeSH headings "physical examination," "personnel management," "occupational medicine," and "personnel selection" yielded 13 articles dealing with the benefit of preemployment examinations to employees or employers. No studies appeared under the text word "preplacement." RESULTS: All of the published articles addressed the protection of the employer in some manner, but only three studies revealed any benefit to the employer or any protective value for the worker. The testing in these three investigations used detailed knowledge of the demands and duties of the job and, therefore, allowed for more task-specific examinations. CONCLUSIONS: The paucity of evidence demonstrating the usefulness of preemployment examinations suggests the need for further research and the development of preemployment evaluations that would allow family physicians to examine employees in a consistently beneficial and more standardized manner. PMID- 1462796 TI - Differences in the obstetric malpractice claims filed by Medicaid and non Medicaid patients. AB - BACKGROUND: Many physicians believe Medicaid patients are more likely than non Medicaid patients to file malpractice claims. This study examines the accuracy of this belief in regard to obstetric malpractice claims. METHODS: Claims filed between January 1982 and June 1988 from the major malpractice insurer in Washington State were used to compare obstetric malpractice claims filed on behalf of Medicaid and non-Medicaid patients. RESULTS: Eleven percent (7/62) of all closed obstetric claims were filed by Medicaid patients, whereas 19 percent of all births in Washington State were to Medicaid patients between 1982 and 1988. Failure to diagnose or treat a fetal condition was the most commonly alleged negligence in both Medicaid and non-Medicaid groups. Most claims in both groups were settled before the cases went to court; a substantial minority of claims were dropped. The mean cost of Medicaid claims ($406,984) was three times that of non-Medicaid claims ($133,743), suggesting that paid Medicaid claims were more severe than paid non-Medicaid claims. CONCLUSIONS: Medicaid patients appear no more likely to file obstetric malpractice claims than non-Medicaid patients. The low likelihood of filing claims, coupled with large settlements, suggests that Medicaid patients may have less access to legal services than non-Medicaid patients. PMID- 1462797 TI - Guidelines for the diagnosis and management of asthma. PMID- 1462798 TI - Hepatitis associated with Lyme disease. PMID- 1462799 TI - Acaridae incognito: the case of the mighty mite. PMID- 1462800 TI - Educational program for premature labor. PMID- 1462801 TI - Models of family practice. PMID- 1462802 TI - The AAFP access plan: getting it almost right. PMID- 1462803 TI - Clinical guidelines and primary care. PMID- 1462804 TI - [Social and family variables related to alcohol consumption]. AB - The present study analyzed some family factors which are considered to be relevant for excessive alcohol consumption. Such analysis is conducted on the data derived from a cross-sectional epidemiological community survey directed to investigate, in a random sample of 1.800 persons of 18 to 65 years of age--and representative of the population of Cantabria--community responses to alcohol consumption. For this we applied among other instruments, a questionnaire designed by the WHO for exploring Alcohol consumption, and which has being extensively used in other countries. We found, among other things, that: i) Among the males excessive alcohol consumption tends to be higher in the single marital status, and also in those with a higher number of brothers; ii) On the females on the contrary, single marital status is associates to higher percentages of non excessive alcohol consumption, while the fact of having a higher number of brothers is related to higher rates of non consumption of alcohol. PMID- 1462805 TI - [The psychiatric emergency in the general hospital: an analysis of the indications for hospitalization]. AB - The following is a study of psychiatric emergencies in a General Hospital in Madrid (Spain). The Psychiatric Emergency Service of the Ramon y Cajal Hospital in Madrid received a total of 3,693 patients in 1988. This was 3.4% of patients seen in the General Emergency Service. The study is based on an analysis of the variables that influence a recommendation of hospitalization and their statistical significance. Hospitalization was recommended more frequently in males and those with diagnoses of depression, alcoholism and schizophrenic or paranoid disorders. PMID- 1462806 TI - [Detoxification treatment with naltrexone in opiate dependence]. AB - Outcome of a maintenance treatment with naltrexone (350 mg/week) are examined in a sample of 50 patients with opiate dependence disorder. Treatment was followed in an outpatient facility, in a setting similar to patient's own environment. The average attendance rate was of 6.4 months. Six months after the onset of the treatment, 46% of the patients still remained drug-free. Results of treatment was correlated with changes in life style of the addicts. A follow-up study found that, overall, the naltrexone treatment caused an increase in alcohol consumption whereas there was a noticeable decrease in cocaine use. Factors related to successful results were a good work adjustment, no use of other drugs and lack of psychopathology. PMID- 1462807 TI - [Premorbid adjustment and negative schizophrenic symptoms]. AB - The relationship between premorbid schizoid traits and the positive and negative symptoms assessed by the Andreasen's SANS and SAPS scales was studied in a sample of 115 DSM-III-R schizophrenics. For the assessment of the schizoid traits the abbreviated Philip's scale of premorbid social-personal adjustment was employed. Negative symptoms, excepting the attentional scale, but no positive symptoms were significantly correlated (p < or = .01) with the Philips's scale. These results suggest that the schizoid traits are the behavioral precursors of schizophrenic negative symptoms. The implications of the results for the genetic and vulnerability/stress models of schizophrenia are discussed. PMID- 1462808 TI - [Lesions of the ureter in obstetric-gynecologic surgery]. AB - The chapter of injuries to the ureter during obstetric-gynaecological surgery continues to be ignored in the literature published over the last decades, in spite of its prevalence in the practice. This has motivated our review and update of this issue. The interest of urological diagnostic procedures prior to surgery and conduit examination at any time during the operation exert some influence on the prevention of this pathology. Preoperative finding and reconstruction lead to better results, which benefit from the use of the urinary route, thus leaving the gut route and self-transplantation for exceptional situations. A new iatrogenic pathology has emerged from the most frequent use of gynaecological endoscopic surgery. PMID- 1462809 TI - [Renal sarcoma]. AB - Among 322 cases of primary malignant renal tumours reviewed between 1969 and 1991, six were renal sarcoma (1.85%). They all presented earlier symptomatology which was not different from other renal tumours, and nephrectomy was performed in all cases, 5 of which died before 14 months. The histopathological diagnose showed two liposarcoma, two carcinosarcomas, all the others being fibrosarcomas. PMID- 1462810 TI - [Evaluation of nuclear roundness as a tool for prostatic carcinoma grading]. AB - The microscopic patterns adopted by prostate carcinomas are extraordinarily variable making its histopathological classification and grading extremely complicated. There are numerous systems for prostatic tumours' grading, but many of them lack a truly reproducible character and an acceptable degree of reliability; for this reason, we have studied a series of nuclear microscopic parameters, from a quantitative point of view, in a series of prostatic carcinomas with a minimum follow-up of five years. It was observed that of the morphometric values obtained--area, perimeter, projection on the X- and Y-axis as well as the nuclear roundness factor--the most useful and representative is the latter. Besides, this is an objective parameter to evaluate nuclear anaplasia and can also be considered as a prognostic factor since, in our series, those who died had a greater mean nuclear roundness factor than those who survived. PMID- 1462811 TI - [Diagnostic efficacy of echographic urethrography in the study of urethral stenosis. Comparison with radiologic retrograde urethrography]. AB - Presentation of the first study on the diagnostic efficacy in the study of stenosis with ultrasound urethrography (U.U.) as compared to X-ray retrograde urethrography (X.R.U.). Sensitivity of U.U. in anterior bulbar urethra is, in general, higher than that of X.R.U. (100 U.U. > 88 X.R.U.) while X.R.U. specificity is higher in the posterior bulbar urethra (100 X.R.U. > 97 U.U.). In penile urethra both techniques showed a 100% diagnostic efficacy. Stenosis located in the posterior bulbar urethra are the most difficult to diagnose with ultrasound techniques. PMID- 1462812 TI - [Extrinsic stenosis of the ureter. Our caseload and review of the literature]. AB - Obstructive uropathy is the common presentation course for various processes with an origin either intraluminar, parietal or extraluminar. A retrospective analysis of 41 cases of extrinsically originated obstructive uropathy seen in our Urology Unit from 1976 to 1991 was carried out. The cases were divided in three groups following an exclusively etiological criterion: 21.9% (9 patients) corresponded to primary retroperitoneal fibrosis; 51.2% (21 patients) to tumoral ureteral obstruction; and 26.8% (11 patients) to non-tumoral processes. For each division established, the features of clinical presentation, performance of the various diagnostic procedures used, and different therapy approaches are described also including a review on the current literature. PMID- 1462813 TI - [Vaginal metastasis of renal cell adenocarcinoma]. PMID- 1462814 TI - [Skin metastasis in prostatic adenocarcinoma]. AB - Skin metastasis of prostatic carcinoma are extremely rare. Presentation of one significant case of these spread. PMID- 1462815 TI - [Retrovesical hydatid cyst. A new case]. AB - Presentation of one case of retrovesical hydatidic cyst with no evidence of hydatidosis in other abdominal organ. Both the case and the medical-surgical procedures performed are described. PMID- 1462816 TI - [Pelvic melanoma]. AB - Report of a patient diagnosed with having a pelvian mass which histologically was a melanoma. Discussion of the possible causes of retrovesical mass and treatment of the melanoma. PMID- 1462817 TI - [Secondary bladder melanoma, presentation of a case]. PMID- 1462818 TI - [Priapism caused by cauda equina compression. Report of a case and review of the literature]. AB - As a result from the mechanical irritation provoked on the sacral roots, the cauda equina compression syndrome can involve, as part of its symptomatic state, involuntary erections and mictional disorders which arise when standing and stretching the spine. In the eight cases of priapism from this cause reported in the international literature, surgical decompression has solved the clinical picture. We now present a new case with the peculiarity that, following unsuccessful surgical therapy, the infiltration of the compromised spinal roots has rendered excellent results. PMID- 1462819 TI - [Embryonal development of interstitial Leydig cells in the rat testis]. AB - Blood testosterone concentrations are not constant throughout life, there being a direct correlation with the numbers of cells producing that hormone, for which reason the existence of two Leydig's cells populations has been proposed: one foetal formation, which disappears just prior or immediately after birth, and a subsequent adult generation. In recent studies, however, that withdrawal has not been observed. Considering all the above, we have studied the evolution of these elements during the rat foetal period. From a morphological point of view Leydig's cells do not differentiate from those in the gonadal interstice until day 17 of pregnancy, showing a considerable increase in their numbers by day 21: while from that day onwards their numbers decrease they never disappear completely. We believe those cells become differentiated from the interstitial mesenchymal cells, and that their increase is facilitated by the proliferation of these same elements. PMID- 1462820 TI - On the mechanism of rat uterus desensitization to kallikrein. AB - An inactive form of kallikrein prepared by iodination with cold iodine, did not show any enzymatic or oxytocic action. However, a competitive pattern between this inactive and active kallikrein was observed in rat uterus preparation: When the inactive form was applied several times in the muscle, a single dose of active kallikrein was unable to cause contraction, but a double dose elicited a response. The rhythmic movement caused by a singular dose of active kallikrein, had its time curtailed by adding the inactive kallikrein to the bath. The inactive kallikrein did not interfere with bradykinin activity. PMID- 1462821 TI - Synthetic substrates and inhibitors for serine proteases from lymphocytes, mast cells, semen, and blood. AB - The substrate specificity of several serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, seminal fluid, and blood plasma has been determined with synthetic peptide thiobenzyl ester and p-nitroanilide substrates. Several new enzymatic activities have been discovered. A variety of inhibitors such as isocoumarins, trifluoromethyl ketones, and peptide chloromethyl ketones were used to study these enzymes and were found to be potent inhibitors. PMID- 1462822 TI - Absorption studies with porcine pancreatic kallikrein in man. AB - Porcine pancreatic kallikrein (PPK), the main component of Padutin (Bayropharm, FRG), is used since 1974 for the treatment of some forms of idiopathic infertility in man. During kallikrein therapy the number of spermatozoa increases, and qualitative and quantitative sperm motility is improved. In order to investigate the intestinal absorption of PPK in man a clinical study with 7 healthy volunteers was performed. 4500 KE (corresp. to 2.8 mg PPK) and 600 KE (corresp. to 0.38 mg PPK) of kallikrein respectively was orally administered in one dosis. Serum and urine samples were collected several times within 24 hours. Seminal plasma was collected 4-5 days before and 8 hours after treatment with kallikrein. Absorbed PPK was determined using a highly sensitive bioluminescence enhanced enzyme immunoassay (1) and a newly developed light measuring equipment (MTP reader) (3). The limit of detection was 1 pg/ml in serum corresponding to 6 amol PPK per assay. For both groups (600 KE and 4500 KE) absorption of PPK in serum was found. Maximum absorption was observed between 4 and 12 h and between 2 and 6h, respectively, after oral application of kallikrein. Renal excretion plays no important role in the elimination of PPK from serum. In gel filtration experiments with blood samples of volunteers in which absorbed PPK was detected, one peak of immunochemically active material corresponding to a molecular mass of 82 kDa was found. According to our results, kallikrein is absorbed in unaltered form by the intestine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462823 TI - The regulating interrelationship of some serine proteinases from leukocyte with the human plasma kallikrein-kinin system. PMID- 1462824 TI - Tissue kallikrein clearance by the liver--effect of plasma components on kallikrein uptake by cultured rat hepatocytes. AB - Rat urinary kallikrein (RUK) injected intravenously to the rat rapidly disappeared from the blood circulation and mainly distributed to the liver. RUK was also incorporated to the primary cultured rat hepatocytes. The amounts of RUK incorporated into the hepatocytes increased by preincubation of RUK with rat plasma. These results and SDS-PAGE analysis suggested some plasma components may be involved in tissue kallikrein clearance in the blood. PMID- 1462825 TI - Tissue kallikrein and the effect of bromocriptine in human prolactin and growth hormone-secreting pituitary adenomas. AB - Tissue kallikrein (TK) is present and co-localises with prolactin producing cells in human prolactinoma and mixed growth hormone (GH) and prolactin-secreting pituitary adenomas. TK immunoreactivity was reduced or absent in these types of adenomas from patients who had received the dopamine agonist, bromocriptine before surgery. Pure GH secreting adenomas had no TK immunoreactivity. PMID- 1462826 TI - Immunomodulators, inflammation and lysosomal proteinases of macrophages. AB - Zymosan-induced stimulation of mononuclear phagocyte system was used as a model for study of inflammation in vivo. Zymosan administration to mice was followed by increase of macrophage enzyme markers beta-N-acetylglucosaminidase and beta-N acetylgalactosaminidase activity in liver and serum. Serum acid glucosidases secretion occurred both after macrophage stimulation by zymosan and macrophage depression induced by GdCl3. Liver granulomatous inflammation resulted increased activity of liver cathepsin B and cathepsin L. There was no changes of cysteine proteinases studied in the case of macrophage depression by GdCl3. The role of lysosomal enzymes secretion in macrophage stimulation and inflammation was discussed. PMID- 1462827 TI - Alpha 1-proteinase inhibitor and resistance to acute blood loss during injection of beta-1,3-carboxymethylglucan. AB - The present study was undertaken to evaluate the mechanism of protective effect of semisoluble alpha-1,3-carboxymethylglucan during massive acute hemorrhage. CBA mice were injected i.v. with glucan (25 mg/kg) 24 h prior to hemorrhage (50% of blood circulating volume). Survival data indicated that glucan increased survival compared with the control. However alpha 1-proteinase inhibitor activity in serum has been even decreased 24 h after glucan administration. Moreover enhancement of active oxygen form production and leakage of cytosolic and lysosomal enzymes after alpha-1,3-carboxymethylglucan application was noted. PMID- 1462828 TI - Protein proteinase inhibitor therapy in experimental pancreatitis: pharmacological characterization of the inhibitor. AB - The pharmacodynamical properties of the duck ovomucoid and its effect on the development of experimental pancreatitis in rats have been studied. It has been shown that after intravenous injection the ovomucoid initially accumulated in the liver, kidneys and blood, while after intraperitoneal injection--mainly in the pancreas and kidneys. The inhibitor is removed from circulation by renal filtration, one-half of the injected protein being removed for 4 hr. For the treatment of experimental pancreatitis two modes of ovomucoid administration were used: intravenous and combined (intravenous/intraperitoneal). The ovomucoid intravenous injection in a dose of 16,300 ATU/kg/24 hr resulted in decrease of both the trypsin-like activity and the level of the trypsinogen activation peptide in the blood to the level in intact rats and also in reduction of the primary pancreas destruction. The same effect observed in the case of the ovomucoid combined injection, but with a lower intravenous dose. PMID- 1462829 TI - The contact activation proteins: a structure/function overview. AB - In recent years, extensive knowledge has been obtained on the structure/function relationships of blood coagulation proteins. In this overview, we present recent developments on the structure/function relationships of the contact activation proteins: factor XII, high molecular weight kininogen, prekallikrein, and factor XI, with the emphasis on the localization of domains on these proteins that are involved in the interaction with activators, substrates and cofactors. PMID- 1462830 TI - Factors affecting the rate of contact activation in human plasma. AB - The rate of high molecular weight kininogen cleavage in human plasma treated with dextran sulfate depends largely on the length of preincubation at 37 degrees C and the sample size during preincubation. The longer the preincubation with aliquots < 100 microliters, the more refractory to contact activation the plasma became. This effect is not due to prekallikrein or factor XII consumption/inhibition since both proteins are functional in clotting assays and detectable in immunoblots even after prolonged incubation times at 37 degrees C. PMID- 1462831 TI - Purification of factor XI and some properties of activated factor XI from porcine plasma. AB - Porcine Factor (F.) XI was purified by following three successive chromatographies. By this procedure, about 5.5 mg of F. XI was obtained from 500 ml of the plasma. The F. XI forms dimer, and is heterogeneous molecule, judging from SDS-polyacrylamide gel electrophoresis. The properties of isolated porcine F. XIa are great similar with those of bovine F. XIa. PMID- 1462832 TI - Human plasma kallikrein processing: proteolysis as an alternative control. AB - Human plasma kallikrein (HuPK) was detected in normal non-activated and dilution activated plasma by immunoblotting, using polyclonal antibodies. In non-activated plasma, the predominatly detected protein corresponds to prokallikrein (Mr 80,000 90,000). Activated plasma, besides kallikrein, contains larger proteins (Mr > 130,000) that possibly represent complexes between kallikrein and proteinase inhibitors. Plasma also contains species (Mr 43,000) which corresponds to kallikrein heavy chain. In activated plasma, monoclonal antibodies against kallikrein heavy chain detected, besides these same bands described above, two additional bands (Mr 30,000 and 20,000) possibly correspondent to fragments of kallikrein heavy chain. PMID- 1462833 TI - Chloramine T impairs the receptor-mediated endocytosis of plasma kallikrein by the liver. AB - Treatment of rat plasma-kallikrein with chloramine T (which does not affect neither its amidolytic activity nor its Mr) impairs the hepatic clearance of the enzyme in a dose-related manner. Preperfusion of the liver with chloramine T before the addition of plasma-kallikrein also diminishes the hepatic clearance of the enzyme. PMID- 1462834 TI - Contact system dependent fibrinolytic activity in vivo: observations in healthy subjects and factor XII deficient patients. AB - The contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in normal plasma was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin alpha 2-antiplasmin (PAP) complexes was lower in factor XII deficient patients than in healthy volunteers. These results indicate that in vivo the plasminogen activating activity is partially dependent on activation of the contact system. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients. PMID- 1462835 TI - Variable depletion of endogenous factor XII-dependent fibrinolytic activity following thrombolytic therapy of myocardial infarction and its relation to reinfarction. PMID- 1462836 TI - Fibrinolysis and extracorporeal circulation. PMID- 1462837 TI - Influence of diabetes mellitus on renal vascular responses to bradykinin. AB - Streptozotocin-induced diabetes resulted in diminished vasodilator responses to bradykinin in the preconstricted isolated perfused kidney of the rat which were associated with decreased renal phospholipase A2 activity and reduced release of PGE2 into the renal venous effluent. PMID- 1462838 TI - Procoagulant changes induced by oral contraceptives are balanced by an increased fibrinolytic tendency. AB - Oral contraceptives caused increased fibrinogen, FVII, FX, and fibrinolysis. The latter was associated with elevated FXII and PKK, while C1-INH was decreased, ATIII and alpha 2M were unchanged; it could not be accounted for by changes in t PA, u-PA, PAI, plasminogen, alpha 2-AP, proteins C or S. HCII and alpha 1-PI were increased and may regulate the availability of thrombin and FXIa. The increased FXII/PKK dependent fibrinolytic potential and HCII may offset any increase in thrombin generation, while alpha 1-PI limits intrinsic coagulation. PMID- 1462839 TI - Studies on blood coagulation-fibrinolysis system regarding kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium. AB - In our previous study (Adv. Exp. Med & Biol., 247B. 569. 1989, 198B. 41. 1986, blood & vessel, 17: 51. 1986), we reported on the mechanism of coagulation fibrinolysis system and kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium. The samples were collected from the uterine artery (UA), uterine vein (UV) and peripheral vein (PV). In this study, we tried to elucidate the mechanism of coagulation fibrinolysis with relation to kks by measuring of Thrombin/Antithrombin III complex (TAT), tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI) complex (tPA.PAI.C), active plasminogen activator inhibitor 1 (active PAI), alpha 2-plasmin inhibitor/plasmin complex (PIC). In 20 normal pregnant women, the levels of TAT, tPA.PAI.C and active PAI significantly increased the first trimester (TAT 4.31 +/- 2.05 ng/ml, tPA.PAI.C 39.52 +/- 17.34 ng/ml, active PAI 39.58 +/- 15.29 ng/ml, n = 20 M +/- SD P < 0.001) to the third trimester (TAT 6.39 +/- 1.93 ng/ml, tPA.PAI.C 57.94 +/- 30.80 ng/ml, active PAI 304.24 +/- 148.64 ng/ml, n = 20 M +/- SD P < 0.001) as compared with those of non pregnant women (TAT 1.60 +/- 0.89 ng/mg, tPA.PAI.C 11.72 +/- 4.59 ng/ml, active PAI 11.53 +/- 7.48 ng/ml, n = 16 M +/- SD). In utero-placental circulation, the levels of TAT significantly increased (TAT 22.12 +/- 20.03 ng/ml n = 20 M +/- SD P < 0.001) in UV, and tPA.PAI.C and PIC. markedly increased (tPA.PAI.C 93.38 +/- 56.05 ng/ml, PIC 1.03 +/- 0.94 micrograms/ml n = 20 M +/- SD P < 0.02) in UV, but active PAI markedly decreased (active PAI 244.18 +/- 87.55 ng/ml n = 20 M +/- SD P < 0.02) as compared with those in PV (TAT 6.1 +/- 2.09 ng/ml, tPA.PAI.C 59.34 +/- 18.99 ng/ml, PIC 0.49 +/- 0.24 micrograms/ml, active PAI 349.14 +/- 157.34 ng/ml, n = 20 M +/- SD). These findings suggest that the significant increase in those complexes in UA has produced a deposition of fibrin clots in the area in contact with utero-placental blood vessel, although the marked increase in tPA.PAI.C and PIC incompletely inhibited the fibrinolytic activity of tPA by the active PAI. The kks shows a consumption of prekallikrein, LMW-kininogen and HMW kininogen, and an overproduction of kinin in UV. PMID- 1462840 TI - Studies of blood coagulation-fibrinolysis regarding kallikrein-kinin system in severe preeclampsia. AB - In our previous study 1), 2), 3) we reported the changes of coagulation fibrinolysis, kallikrein-kinin system and kininase in preclampsis. In this study, we tried to obtain systemic information of chronic DIC status with regard to kallikrein-kinin system in severe preeclampsia. This systemic information was evaluated in 20 cases of normal gravidas from 28 to 42 weeks of gestation as a control by measuring plasma Thrombin/Antithrombin III complex (TAT), tissue plasminogen activator (tPA) plasminogen activator inhibitor (PAI) complex, active plasminogen inhibitor-1 (active PAI), 2PI plasmin complex (PIC). RESULTS: The levels of plasma TAT and tPA significantly increased (TAT = 10.9 +/- 8.3 ng/ml n = 24 M +/- SD P < 0.02, tPA = 6.1 +/- 3.2 ng/ml n = 10 M +/- SD P < 0.01), tPA PAI C and active PAI markedly increased (tPA PAI C = 85.07 +/- 50.01 ng/ml n = 24 P < 0.05, active PAI = 407.4 +/- 166.0 ng/ml n = 24 P < 0.205), and PIC and D dimer = 435.1 +/- 145.2 ng/ml n = 8 M +/- SD P < 0.001) in severe preeclampsia as compared with those of normal values (TAT = 6.1 2.0 ng/ml, tPA = 3.6 +/- 1.5 ng/ml, tPA PAI C = 57.9 +/- 30.8 ng/ml, active PAI = 304.2 +/- 148.6 ng/ml, PIC = 0.49 +/- 0.24 mg/ml, D-dimer = 282.9 +/- 75.3 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462841 TI - Bradykinin-mediated metabolic effects in isolated perfused rat hearts. AB - Bradykinin perfusion (BK 1 x 10(-12) to 1 x 10(-8) mol/l) of isolated working rat hearts with postischemic reperfusion arrhythmias induced a reduction of the incidence as well as duration of ventricular fibrillation, improvement of cardiodynamics via increased left ventricular pressure, contractility, and coronary flow without changes in heart rate. These beneficial effects were accompanied by reduced activities of the cytosolic enzymes lactate dehydrogenase and creatine kinase as well as lactate output. In the myocardial tissue lactate content was reduced and the energy rich phosphates increased compared to saline perfused control hearts. Glycogen stores were also preserved. These beneficial effects of BK were concentration-dependently abolished by perfusion of the B2 kinin receptor antagonist HOE 140 and the nitric oxide (NO) synthase inhibitor NG nitro-L-arginine (L-NNA). These results suggest that improved cardiac function during and after myocardial ischemia as well as increased energy rich phophates and glycogen stores are mediated by BK and the subsequent release of NO, shifting myocardial metabolism during ischemia and reperfusion to the glucose pathway which leads to changes indicative for cardioprotection. PMID- 1462842 TI - Evidence that nitric oxide or a related substance is a neurovasodilator in the submandibular gland of the cat. AB - Close-arterial injection of L-NG-nitro arginine methyl ester, a compound that inhibits the synthesis of nitric oxide (NO), caused a dose-dependent reduction in both the parasympathetic and sympathetic (rebound) nerve-induced vasodilatation within the submandibular gland of the cat. At the same time, salivary secretion produced by each nerve was relatively unaffected, and the sympathetic vasoconstriction was enhanced. These results suggest that NO or a related compound may be either a neurotransmitter or neuromodulator contributing to the autonomic nerve-induced vasodilatation in the submandibular gland of the cat. PMID- 1462843 TI - Increased sensitivity of guinea pig gallbladder in vitro to bradykinin. AB - Bradykinin evoked concentration dependent contractions of guinea pig gallbladder smooth muscle strips in vitro. Responses to kinins increase over three hours of incubation. Induction of a B1-mediated action, waning activity of endogenous kininase(s) and involvement of eicosanoids as mediators have been investigated as potential contributing mechanisms to the four-fold, time dependent increase in response of this tissue to bradykinin. PMID- 1462844 TI - Involvement of bradykinin-induced [Ca2+]i oscillations in phosphatidylcholine breakdown in K-ras-transformed fibroblasts. AB - Bradykinin (BK) induced a biphasic 1,2-diacylglycerol production in both K-ras transformed (DT) cells and its parent NIH3T3 cells. The first phase was coincident with the transient phosphoinositide turnover and the second sustained phase was derived from hydrolysis of phosphatidylcholine (PC). In DT cells, the PC breakdown was considerably due to phospholipase C and dependent on intracellular calcium oscillations. PMID- 1462845 TI - Renal alteration and development of hypertension in diabetic rats. AB - There is a close association between diabetes and hypertension. Many studies have demonstrated an increased incidence of hypertension in the presence of diabetic nephropathy. The aim of the present work was to study the kallikrein-kinin system during the diabetic states with hypertension. In this study neonatal rats were injected with streptozotocin at two days of age. Plasma glucose, proteinuria, urinary kallikrein, blood pressure, creatinine clearance, diuresis and body weight were measured. RESULTS: control rats vs diabetic rats. Plasma glucose (mg/dl): 0 minutes 80.2 +/- 2.5 vs 105.5 +/- 4.5; 60 minutes 120.4 +/- 2.3 vs 220.0 +/- 4.6; 120 minutes 105.0 +/- 1.5 vs 140.0 +/- 3.6; p < 0.05. Proteinuria at 8 months of age (mg/24 hs): 12.5 +/- 1.6 vs 20.6 +/- 2.4; p < 0.05. Urinary kallikrein at 8 months of age (umol/min/24 hs)/(ml/min) x 10(3): 46.9 +/- 3.0 vs 28.5 +/- 2.5; p 0.005. Blood pressure at 8 months of age (mm Hg): 110.0 +/- 2.0 vs 132.0 +/- 4.0; p < 0.001. Creatinine clearance at 10 months of age (ml/min): 0.46 +/- 0.03 vs 0.70 +/- 0.14; p < 0.05. Diuresis at 8 months of age (ml/24 hs): 1.55 +/- 0.65 vs 10.30 +/- 1.44, p < 0.001. The early modifications of kallikrein kinin system in the diabetes states may contribute to development hypertension with modifications in the hemodynamics renal function. PMID- 1462846 TI - Isolation of a thiol-dependent acid kininogenase from rat spleen. AB - The enzyme which could produce kinin-like peptides from rat plasma at acidic condition and at coexistence of thiol compound was separated from acid extract of rat spleen. The isolation procedure of this enzyme was established. Substrate specificity was examined against fluologenic substrates and two types of collagen. The purified enzyme was proved to have kinin-forming activity and also collagenlytic activity. PMID- 1462847 TI - Cell membrane potential oscillations induced by kinins in fibroblasts expressing the Ha-ras oncogene. AB - In NIH-3T3 fibroblasts expressing the ras oncogene (+ras) bradykinin (BK) elicits sustained oscillations (1/min) of cell membrane potential (PD) due to oscillations of intracellular calcium activity with subsequent activation of calcium sensitive K+ channels. In NIH-3T3 fibroblasts not expressing the oncogene (-ras), BK leads to a single transient hyperpolarization of the cell membrane, not followed by oscillations. The oscillations of cell membrane potential require the presence of extracellular calcium and are abolished by K+ channel blocker barium (1 mmol/l), as well as by calcium channel blockers cadmium (1 mmol/l), lanthanum (0.1 mmol/l) and nifedipine (10 mumol/l). However, the oscillations are not modified by 1 mumol/l nifedipine, or by other calcium channel blockers, such as verapamil (10 mumol/l) or diltiazem (10 mumol/l). Cell proliferation is inhibited by nifedipine (10 mumol/l) but not by verapamil or diltiazem, indicating that the oscillations of intracellular calcium are a prerequisite for the growth factor independent proliferation of ras oncogene expressing cells. PMID- 1462848 TI - Regulation of bradykinin-induced chloride secretion in a human epithelial cell line. AB - The chloride secretory response to bradykinin in T84 cells is regulated. The efflux rate of 125I from these cells can be used to measure this response, and to demonstrate that the sensitivity to bradykinin varies with time in culture. The response in NuT84 cells is greater than that in T84, and can be blocked by the B2 receptor antagonist HOE-140. PMID- 1462849 TI - Desensitization of bradykinin-induced activation of peripheral nociceptors. AB - Bradykinin-induced activation of peripheral nociceptors has been studied in an isolated spinal cord/tail preparation from the neonatal rat. Prolonged administration of bradykinin consistently produced a selective desensitization which could be prevented by concanavalin A but not by succinyl concanavalin A or phenylarsine oxide. These data indicate that mannose-containing glycoproteins occur in or close to the bradykinin receptor site. In addition the desensitization observed under the present conditions, did not involve the internalization of bradykinin receptors. PMID- 1462850 TI - The kallikrein--kinin system in blood vessels. AB - We have previously reported that vascular tissue contains kallikrein and kallikrein mRNA. We can now show that kallikrein is present throughout the vascular tree and is released from arterial and venous rings incubated "in vitro". Using the isolated perfused rat hindquarters as a model, we found that kallikrein appeared in the perfusate in concentrations that increased linearly with time. Treatment with puromycin inhibited kallikrein release by 87% (p < 0.01), these data suggest that kallikrein is synthesized and released by the vascular wall. Local generation of kinins (autocrine/paracrine system) may contribute to the regulation of vascular homeostasis. PMID- 1462851 TI - Vascular wall kininogen concentration is inversely related to intrinsic kininogenase in spontaneously hypertensive rats. AB - We determined kininogen concentration and kininogenase activity in the blood free, aorta homogenates of 15 week old spontaneously hypertensive rats (SHR) and in their age-matched wistar kyoto (WKY) controls. Active kininogenase in the SHR was only 18% of the WKY controls. Thus, the kininogen concentration was inversely related to kininogenase activity suggesting a local interaction of these components and possible generation of kinins within the vascular wall. PMID- 1462852 TI - Effects of bradykinin and Des-Arg9-bradykinin on the ischemic rat heart. AB - In isolated rat hearts subjected to 30 min stop flow followed by 5 min reperfusion, Bradykinin (Bk), 1 and 0.1 microM, significantly decreased ventricular tachycardia and fibrillation, noradrenaline (NA) output at reperfusion as well as myocardial NA loss and lipid peroxidation, and preserved creatine kinase activity. Des-Arg9-Bk 0.1 microM had also similar effects. Hence, the active metabolite des-Arg9-Bk may be involved in the protective action of Bk, partly mediated by its inhibitory effect on NA liberation. PMID- 1462853 TI - The effect of bradykinin on coronary flow and its potentiation by SH-containing ACE-inhibitors. AB - Bradykinin plays a role in the regulation of coronary blood flow. Under basic conditions the vasodilating effect is primarily mediated by stimulation of the endogenous nitrovasodilator endothelium-derived relaxing factor (EDRF). This effect is shortlasting but can be increased and prolonged by sulfhydryl(SH) containing agents. ACE-inhibitors may cause coronary vasorelaxation by a bradykinin-mediated release of EDRF. This can be potentiated by the presence of SH-groups, as was shown with captopril and zofenoprilat. As a consequence, SH containing ACE-inhibitors may potentiate nitrates, because they act as exogenous nitrovasodilators, and reverse tolerance to their therapeutic effect. PMID- 1462854 TI - Direct effects of bradykinin on glomerular filtration and proximal tubule reabsorption in rat kidney. AB - Intrarenal infusion of a low dose of bradykinin devoid of extrarenal action exerts direct vasodilator and diuretic effects on rat kidney. It does not significantly alter glomerular filtration rate and absolute proximal reabsorption but increases the delivery of fluid from the proximal tubule evaluated by the clearance of lithium. None of these effects are observed in kidneys infused with both bradykinin and a specific bradykinin antagonist. PMID- 1462855 TI - Kallikrein and kinin release using superfused disaggregated cortical cells from rat and human kidney: effects of AVP and dopamine. AB - Potential regulators of the renal Kallikrein-Kinin System are poorly defined. We have therefore examined the effect of arginine vasopressin and dopamine on the release of kallikrein and kinin from collagenase-dispersed rat and human renal cortical cells. PMID- 1462856 TI - Kinin antagonist blunts the diuretic effect of furosemide in deoxycorticosterone treated rats. AB - Furosemide at a dose of 3 mg/kg body wt increased urinary volume (vehicle: 12.8 +/- 0.6; furosemide: 42.4 +/- 2.6 ml/8h, p < 0.01) and urinary sodium excretion (vehicle: 0.9 +/- 0.1; furosemide: 5.0 +/- 0.4 mM/8h, p < 0.01) in deoxycorticosterone-treated rats. These effects were associated to a decrease in mean blood pressure (from 122 +/- 4 to 113 +/- 3 mmHg, p < 0.01) and renal vascular resistances (from 15.6 +/- 0.6 to 14.3 +/- 0.7 RU, p < 0.05). The B2 receptor antagonist D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin significantly blunted the diuretic and natriuretic effect of furosemide and completely prevented the decrease in blood pressure and renal vascular resistances. The renal kallikrein kinin system may modulate the diuretic and hemodynamic effects of furosemide in conditions of increased mineralcorticoid activity. PMID- 1462857 TI - ACE inhibitor effect on bradykinin metabolism in the vascular wall. AB - In the isolated rabbit thoracic aorta the ACE inhibitor ramiprilat attenuated bradykinin degradation by enzymes localized on vascular endothelial cells as well as on vascular smooth muscle cells by 26% and 32%, respectively. We conclude that the ACE inhibitor can attenuate vascular bradykinin degradation not only by inhibition of endothelial ACE but also by inhibition of other bradykinin degrading enzymes in deeper layers of the vascular wall. PMID- 1462858 TI - Local production of kinins contributes to the endothelium dependent relaxations evoked by converting enzyme inhibitors in isolated arteries. AB - The angiotensin converting enzyme (ACE) inhibitor perindoprilat evokes endothelium-dependent relaxations in perfused isolated canine arteries. Kininogens, the precursors of bradykinin, elicit endothelium-dependent relaxations which are potentiated by perindoprilat, inhibited by B2-kinin antagonists and partially impaired after inhibition of NO synthase. These observations suggest that locally produced kinins may stimulate the production of NO and endothelium-derived hyperpolarizing factor, and that this action is potentiated by ACE inhibitors. PMID- 1462859 TI - Captopril as a modifier of the arachidonate cascade of rat platelets. AB - The lipoxygenase pathway of arachidonate cascade in the platelets of spontaneously hypertensive rats has been found to be significantly higher than in normotensive animals. Repeated oral administration of Captopril (in drinking water - 200 mg/100 ml) for 14 days resulted in an elevation in the activity of arachidonate cascade in the platelets of treated rats. At the same time the Captopril treatment induced the formation of 12-hydroxy-heptadecatrienoic acid (12-HHT), which molecule is known to be a potent prostacyclin (PGI2) releaser and/or synthesis inducer. PGI2 is one of the most potent vasodilatator molecule in living organisms. The in vitro experiments in rat platelets suggest, that very low doses of Captopril (10(-12) to 10(-10) M) result in a significantly elevated 12-HHT synthesis. Captopril might act through the 12-HHT--PGI2 mechanism, resulting in blood pressure reduction. The lipoxygenase pathway of platelets, the formation of 12-hydroxyeicosatetraenoic acid (12-HETE), was significantly elevated in vitro in the presence of low dose of Captopril (10(-11) and 10(-10) M). PMID- 1462860 TI - Cardioprotection of ACE inhibitor in ischemic heart is not dependent on the local angiotensin II formation. AB - Angiotensin II (AII) and bradykinin (BK) release into anterior interventricular vein (AIV) increased significantly 30 minutes after left anterior descending artery (LAD) occlusion in the absence of kidneys. Captopril enhanced BK release, but did not suppress the increase of AII release. Nafamostat suppressed both releases. Infarct size was significantly reduced by captopril but not by nafamostat. These results suggest that cardioprotective effect of captopril might be dependent on local BK accumulation, but not on suppression of local AII generation. PMID- 1462861 TI - Salt sensitivity and bradykinin activity in rats. PMID- 1462862 TI - Action of a novel kinin precursor, Met-T-kinin-Leu, on prostaglandin I2 and blood pressure. AB - The novel kinin precursor, Met-T-kinin-Leu, stimulated the release of prostaglandin I2 from endothelial cells cultured using bovine carotid artery endothelial cells and minimum essential medium supplemented with 10% fetal calf serum. However, it failed to stimulate the release of prostaglandin I2 from the cells in the fetal calf serum-free medium conditions. To examine the discrepancy of the release of prostaglandin I2 from the cells by Met-T-kinin-Leu in the presence or absence of fetal calf serum, the products formed from Met-T-kinin-Leu by incubation of culture medium were analyzed by reverse-phase HPLC. Regarding the blood pressure reaction of Met-T-kinin-Leu, it showed from one fifth to one hundredth of that compared with bradykinin in blood pressure reactivity of each species, such as rats, rabbits and cats. PMID- 1462863 TI - The renal kallikrein-kinin system at the prehypertensive stage of hypertension. AB - In essential hypertension, renal dopaminergic activity and PGE2 was suppressed as was the renal kallikrein-kinin system. The suppression of the renal depressor systems may play an important role in the etiology of hypertension through sodium and body fluid retention. At the prehypertensive stage of essential hypertension, renal dopaminergic activity was suppressed, which induced the retention of body fluids and sodium. On the other hand, the renal prostaglandin E2 was augmented, and it seemed to be a compensatory mechanism for sodium retention. We could not confirm the suppression of the renal kallikrein-kinin system at the prehypertensive stage of hypertension. Although all renal depressor systems are suppressed in essential hypertension, the suppression of the renal kallikrein kinin system and PGE2 seem to be very important in the etiology of hypertension. Further study is necessary to clarify when both systems are suppressed. PMID- 1462864 TI - Lack of oral kallikrein in lowering systemic blood pressure in primary hypertension. AB - Primary hypertension is associated with a lack in renal kallikrein activity which might be one of the reasons for the blood pressure elevation. Some smaller and partially uncontrolled studies suggested that an oral substitution of glandular kallikrein lowers blood pressure by a kinin-mediated vasodilation and increased natriuresis. To test this hypothesis we treated in two studies over 100 patients with untreated mild to moderate primary hypertension (WHO I-II) for 5 resp. 12 weeks in a double blind randomized and placebo controlled manner with 1800 U glandular kallikrein orally. Blood pressure measurements were performed according to the two study designs after 3 and 5 resp. 8 and 12 weeks of treatment sphymomanometrically in the day time course. No significant changes in blood pressure by kallikrein treatment could be observed at any time. Neither renal kallikrein excretion, renin and ACE-activity nor blood glucose concentration in diabetics or non-diabetics was changed. Thus, we could undoubtedly demonstrate that oral applied glandular kallikrein has no effect on primary hypertension. PMID- 1462865 TI - The kallikrein-kinin system in early state of diabetes. AB - The kallikrein-kinin system was studied in 9 normals, healthy subjects (6 men, 3 women, age range 1 to 14 years) and 15 diabetic patients (9 men, 6 women age range 2 to 14 years) with an evolution of the disease between 1 to 14 years. Diabetic patients with low microalbuminuria (6.62 +/- 0.97 mg/24 h) show increased total and pre-kallikrein respect to control (3 and 2 fold respectively). On the other hand patients with high microalbuminuria (44.7 +/- 13.2 mg/24 h) show a total and pre-kallikrein of more than 4 and 8 fold increased respectively, compare with the control. According with these results we can concluded: 1) The total kallikrein and pre-kallikrein is increased in the diabetic state. 2) When microalbuminuria is high, the total and pre-kallikrein correlates with those increasing. 3) These changes could modified the renal hemodynamic in diabetes. PMID- 1462866 TI - Studies of the activation and inhibition of the plasma kallikrein-kinin system. PMID- 1462867 TI - Hageman factor dependent activation and its relationship to lethal Pseudomonas aeruginosa burn wound infections. AB - Trauma causes increases in total protease load in the circulation of the traumatized host animal or patient. This increase is due, in part, to Hageman Factor activation followed by down-line cascade system activation. Concomitant with the activation of these systems is a reduced host capacity to resist infection. Infection superimposed on a traumatized host increases the total host protease load even more by additional activation of Hageman Factor and cascade systems. PMID- 1462868 TI - Microbial proteinases as an universal trigger of kinin generation in microbial infections. PMID- 1462869 TI - Liver and serum lysosomal enzymes activity during zymosan-induced inflammation in mice. AB - Liver and serum lysosomal enzymes (acid glucosidases and cysteine proteinases) during zymosan-induced stimulation of MPS or MPR depression induced by GdCl3 have been studied. Zymosan was used as a model for study of inflammation in vivo. The development of inflammation induced by zymosan was followed by increase activity of macrophage activation markers - beta-N-acetylglucosaminidase (NAGlu) and beta N-acetylgalactosaminidase (NAGal) in liver and serum. There was enhance of liver cysteine proteinases activity. Similar, less prominent (partly) data were obtained during macrophage depression induced by GdCl3. PMID- 1462870 TI - Plasma exudation by activated plasma kallikrein after intraperitoneal injection of lambda-carrageenin or endotoxin in rats. AB - The experimental study was carried out to examine whether intraperitoneal injection of carrageenin or endotoxin activates plasma kallikrein-kinin system to induce plasma exudation in rats. Intraperitoneal injection of 2% lambda carrageenin induced plasma exudation in the peritoneal cavity by activation of plasma prekallikrein. Intraperitoneal injection of endotoxin (3mg/kg) also resulted in intraperitoneal plasma exudation, but plasma kallikrein-kinin system did not seem to be involved. PMID- 1462871 TI - The role of alpha 1-proteinase inhibitor in semisoluble glucan induced resistance to hemorrhage. AB - The present study was undertaken to evaluate the mechanism of protective effect of semisoluble beta-1,3-carboxymethylglucan (CMG) during acute massive hemorrhage. CBA mice were injected i.v. with glucan (25 mg/kg) 24 h prior to hemorrhage (50% of blood circulating volume). Survival data indicated that glucan increased survival compared with control. However, alpha 1-proteinase inhibitor activity in serum have been even decreased 24 h after glucan administration. Moreover enhancement of active oxygen form production and leakage of cytosol and lysosomal enzymes after CMG application were noted. PMID- 1462872 TI - Determination of tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complexes in synovial fluid of patients with rheumatoid, osteo and psoriatic arthritis. AB - An enzyme-linked immunosorbant assay was developed to determine tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complexes in pooled synovial fluid of patients with rheumatoid, osteo and psoriatic arthritis. Even though basal values could be determined, the addition of synovial fluid shifted the standard curves for both tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complex to the right, because of the presence of a novel inhibitor. PMID- 1462873 TI - Comparison of plasma prekallikrein levels in human skin blister and chamber fluids from volunteer subjects and psoriatic patients. AB - Suction blisters were successfully raised on lesional, perilesional and non lesional skin of psoriatic patients. Similar blisters were created on the skin of volunteer subjects. A specific method has been established for the measurement of plasma prekallikrein, and validated for blister fluid, skin chamber fluid, plasma and synovial fluid. Combined levels of plasma prekallikrein and its active form were compared in blister fluids obtained from psoriatic patients and the volunteers. Significantly higher values for plasma prekallikrein were found in the non-lesional blister fluids of psoriatic patients when compared to the volunteer subjects. PMID- 1462874 TI - Changes in polymorphonuclear neutrophil-elastase in pancreatitis. AB - In cases of acute and chronic pancreatitis, we measured the amount of polymorphonuclear neutrophil (PMN)-elastase. There was a significantly larger increase in PMN-elastase in patients with pancreatitis than normal adults. Especially, there was a particularly notable increase in amount of PMN-elastase in patients with severe pancreatitis. Furthermore, the peak of PMN-elastase increase throughout the course of the pancreatitis was seen to be 1-2 days after peak increase in pancreatic enzymes. In the experiment in which pancreatic juice and pig pancreatic kallikrein were added to granulocytes in vitro, we recognized a gradual release of PMN-elastase. From these data, we suggested that timely measurements of PMN-elastase are useful to marker of monitoring clinical changes in severe pancreatitis. PMID- 1462875 TI - CP-0127, a novel potent bradykinin antagonist, increases survival in rat and rabbit models of endotoxin shock. AB - The bradykinin antagonist dimer CP-0127 was found to be a potent and selective inhibitor of the depressor response to bradykinin in the anaesthetized rat and rabbit. When given as a single dose s.c. (3.6 mumol/kg), the depressor response to bradykinin was blocked for the duration of the experiment (4 hours). In anaesthetized control rats, LPS from E. coli produced a profound and immediate hypotensive response, while in rats infused with CP-0127, the response to LPS was almost totally reversed. In addition, CP-0127 given as a single subcutaneous dose (3.6 mumol/kg) to rats 1 hour before LPS challenge produced a 93% survival rate, compared to 14% in control animals. Finally, a survival rate of 86% was achieved in rabbits infused with CP-0127 at 0.36 nmol/kg/min i.v., compared to 45.5% in saline-infused control animals given LPS (500 micrograms/kg i.v.). The results of these experiments provide evidence for a significant role for the kallikrein kinin system in these models of endotoxic shock, and indicate the therapeutic potential of a bradykinin antagonist such as CP-0127 for treating this disorder in man. PMID- 1462876 TI - The bradykinin antagonist Hoe 140 inhibits carrageenan- and thermically induced paw oedema in rats. AB - The new and highly potent B2 bradykinin (BK) antagonist Hoe 140 was tested for its ability to inhibit oedema of rat paws induced by scalding and carrageenan. The data show that Hoe 140 inhibits scalding and carrageenan oedema for more than four and six hours, respectively. Based on its potency against actions of endogenously generated kinins Hoe 140 is appropriate to investigate the role of kinins in human inflammatory diseases. PMID- 1462877 TI - Effect of bradykinin on airway function. AB - Bradykinin (BK) has several effects on airway function which may be relevant in obstructive airways disease. These effects are mediated via B2-receptors. BK is a potent bronchoconstrictor in animals and humans in vivo. Bradykinin contracts airway smooth muscle, is a potent bronchial vasodilator, increases microvascular leakage, stimulates epithelial cells to release bronchodilators and stimulates mucus secretion. Perhaps its most important action is the activation of sensory nerves in airways, leading to reflex bronchoconstriction, coughing and neurogenic inflammation through the release of neuropeptides from sensory nerves. PMID- 1462878 TI - The potential role of bradykinin antagonists in the treatment of asthma. AB - The potential role of bradykinin and the use of bradykinin antagonists in the treatment of allergic airway disease (asthma) was studied by determining the effects of the bradykinin B2 receptor antagonist, NPC-567 (D-Arg-[Hyp3,D-Phe7] bradykinin) on antigen-induced early and late bronchial responses, airway inflammation, mediator release and airway hyperresponsiveness in the sheep model of allergic asthma. In the control trial, antigen challenge produced an early bronchoconstrictor response that was associated with an increase in immunoreactive-kinins in bronchoalveolar lavage fluid (BAL), and a late bronchial response that was associated with increased concentrations of leukotriene [LT]B4 and LTC4 and inflammatory cells (neutrophils and eosinophils) in the BAL. Aerosol NPC-567 given before, during and 4 h after antigen challenge had no protective effect on the early bronchoconstrictor response, but significantly inhibited the late bronchial response. This inhibition was correlated with a reduction in the inflammatory lipid mediators and inflammatory cells in BAL. These results suggest that antigen-induced kinin generation may be important for controlling the release of arachidonic acid metabolites from inflammatory cells that contribute to the development of late responses and airway hyperresponsiveness. PMID- 1462879 TI - Kallikrein-like activity in the bronchoalveolar lavage (BAL) fluid of sensitized, challenged guinea-pigs. AB - Sensitization and challenge of guinea-pig airways with aerosols of ovalbumin solution administered through an endotracheal tube leads to a significant increase in kallikrein-like enzyme activity in bronchoalveolar lavage (BAL) fluid. This increase is present up to six hours after challenge and may be related to changes in airways resistance that persist for similar periods. PMID- 1462880 TI - Increase in the kinin levels in the bronchial washings after intravenous injection of leukotriene C4 in guinea pigs. AB - In guinea pig plasma, bradykinin (BK) was degraded mainly to des-Arg1-BK by an aminopeptidase-like enzyme, which was inhibited by 2-mercaptoethanol. Besides this degradation, BK was also hydrolyzed by kininase I and kininase II from C terminal end to des-Arg9-BK, des-Phe8-Arg9-BK and Arg-Pro-Pro-Gly-Phe ([1-5] BK). The formation of des-9-BK was strongly blocked by DL-2-mercaptomethyl-3 guanidinoethylthiopropanoic acid (MGPA) and that of des-8,9-BK and [1-5] BK was inhibited by captopril. When guinea pigs were pretreated with a cocktail of 2 mercaptoethanol, MGPA and captopril, intravenous administration of leukotriene (LT) C4 (10 nmol/kg) caused an increase in the levels of free kinin in the bronchial washings of guinea pigs. This increase was accompanied with the increase in glandular-kallikrein activity, which could be inhibited by aprotinin. As BK is reported to induce both bronchoconstriction and bronchial secretion, the increased free BK induced by LTC4 might enhance the effect of LTC4. PMID- 1462881 TI - Bradykinin and other inflammatory mediators in BAL-fluid from patients with active pulmonary inflammation. AB - We evaluated the levels of bradykinin, albumin, TAME-esterase activity, histamine, PGD2 and LTC4 in bronchoalveolar lavage fluid from asthmatics and from patients with pneumonia, sarcoidosis, fibrosis, and chronic bronchitis. Compared with the results of healthy volunteers and atopic asymptomatic asthmatics the bradykinin levels and TAME-esterase activity were significantly elevated. In all other groups, histamine was additionally elevated in asymptomatic asthmatics, whereas albumin was elevated in symptomatic asthmatics and fibrosis patients, and decreased in chronic bronchitis and pneumonia patients. Following local intrabronchial allergen challenge of mild grass pollen asthmatics out of season bradykinin levels increased significantly, correlated with albumin, histamine and TAME-esterase activity. In contrast to the increased mediator concentrations in the early phase reaction there was no change of BAL cells in asthmatics compared to baseline and healthy volunteers. The presence of bradykinin in the bronchoalveolar space of patients with active pulmonary inflammations and bradykinin generation in asthmatics as a result of intrabronchial allergen challenge provides strong evidence that kinins are involved in inflammatory disorders of the lower airways. PMID- 1462882 TI - Cough induced by ACE-inhibitors. A kinin related phenomenon? AB - Cough induced by ACE-inhibitors may be related to bronchial hyperreactivity and/or to an accumulation of kinins. In a placebo-controlled, double-blind randomized study in asthmatic and hypertensive patients lung function and bronchial reactivity to histamine and bradykinin remained unaltered although in hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. The findings do not support a major role of kinins in ACE inhibitor-induced cough. PMID- 1462883 TI - The kallikrein-kinin system of sweat in normal and cystic fibrosis subjects. AB - The mechanisms of kallikrein secretion was studied in 25 normal subjects (11 male, 14 female) and 5 subjects with cystic fibrosis (identified by the usual criteria). The results obtained show a decreasing of prekallikrein and total kallikrein in cystic fibrosis stimulated by IPR or pilocarpine compare to controls. On the other hand sweat from males shows more prekallikrein and total kallikrein than females. According with this results we can concluded that the basic defect in sweat cystic fibrosis gland could be the possible involvement of the kallikrein-kinin system on the high osmolality of the sweat secretion. PMID- 1462884 TI - Modulation of presynaptic sympathetic activity by kinins and related compounds: influence of converting enzyme inhibition. AB - Since converting enzyme and kininase II are identical enzymes and probably influences both, the biosynthesis of Ang II and the metabolism of bradykinin we investigated the effects of bradykinin, desArg-bradykinin and some bradykinin antagonists (desArg[9]-Leu[8]-bradykinin, HOE S 890307) on the sympathetic outflow of pithed SHR or Brown-Norway-Rats before and after acute or chronic inhibition of the converting enzyme by ramipril. bradykinin increased dose dependently the noradrenaline and adrenaline release in particular when the converting enzyme was inhibited. DesArg-bradykinin caused a dose-dependent increase in adrenaline release only after converting enzyme inhibition. The bradykinin-antagonists led to an increase in adrenaline release during ramipril administration. The weak but significant stimulation of adrenaline release by the bradykinin antagonists after converting enzyme inhibition might be due to unspecific actions on the adrenal medulla possibly induced by histamine release from mast cells. PMID- 1462885 TI - The kallikrein-kinin system in cardiac tissue. AB - Kallikrein and minute amounts of kininogen have been found in rat cardiac tissue. The mRNA for kallikrein was also determined by the polymerase chain reaction using KK-specific probe. The existence of an intrinsic kallikrein-kinin system in the heart raises the possibility that the enzyme-peptide system is involved in local regulation of cardiac function and metabolism. PMID- 1462886 TI - Early ACE-inhibition in myocardial infarction. Possible role of bradykinin. AB - Restoration of coronary blood flow in the ischemic myocardium is absolutely needed to prevent irreversible cellular damage but on the other hand may have potentially hazardous consequences. Since thrombolysis during myocardial infarction is designed to salvage a maximal number of myocardial cells threatened by ischemia, a concommitant intervention which reduces cellular damage due to reperfusion will improve the net result of such procedure. The adjunctive use of ACE-inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. This article summarizes the results indicating that ACE-inhibitors do play an important role in cardioprotection in the acute phase of myocardial ischemia followed by reperfusion. Probably, their effect on bradykinin breakdown is at least partly responsible for this effect. PMID- 1462887 TI - Activation of kinins on myocardial ischemia. AB - In experimental ischemic dog heart with coronary-constriction, no increase of coronary blood flow, Max dP/dt or MVO2 with no change of kinin in arterial blood were exhibited. Following sympathetic nerve stimulation, remarkable increases of kinin in coronary sinus blood were observed with a significant elevation of left ventricular end-diastolic pressure and an augmented production of lactate from the heart as well as an ischemic change of ECG-ST. Infusion of kinin into the left main coronary artery resulted in no change in the mean systemic blood pressure, coronary blood flow, coronary vascular resistance, cardiac function, myocardial metabolism or ECG-ST in the control and coronary-constricted groups. These data suggest that kinin was released significantly from the ischemic heart, however, such a level of kinin has no significant effect on coronary circulation or myocardial metabolism. In ischemia-reperfusion rabbit hearts, no significant influence of the ACE inhibitors, captopril and ramiprilat, were observed. Species differences may be responsible for the beneficial role of ACE inhibitors in the limitation of infarct size in the dog hearts, possessing collateral flow, that are not seen in the rabbit heart with poor collateral flow. PMID- 1462888 TI - The possible role of bradykinin in the antiischemic activity of ACE-inhibitors. AB - The ACE-inhibitor ramiprilat (40 ng/kg/min) was infused for 6 h into the left coronary artery of anesthetized dogs with ligation of the descending branch of this artery. This route of administration and the low dose were chosen to achieve local cardiac effects without affecting systemic hemodynamics. Ramiprilat significantly reduced infarct-size expressed as percentage of the area at risk. The cardioprotective effect of ramiprilat was mimicked by bradykinin and abolished by coadministration of a bradykinin antagonist. These results strongly suggest that bradykinin plays a role in the cardioprotective effect of the ACE inhibitor ramiprilat. PMID- 1462889 TI - Aesthetic maxillo-facial surgery: face lifting and S.M.A.S. AB - The article illustrates the importance of face lifting and S.M.A.S. tightening as an adjunct to the aesthetic aspect of maxillo facial surgery, for instance in combination with extreme mandibular set back or advancement in adults. The theory and basic techniques of the face lifting procedure and the S.M.A.S. tightening technique are described. A clinical example is presented. The indications pre- and postoperative management and complications have been mentioned. PMID- 1462890 TI - Submental liposuction in maxillo-facial surgery. AB - Liposuction is a relatively recent surgical technique used in body contouring plastic surgery to correct fatty dysharmonies. It is of particular interest to the maxillo-facial surgeon to treat submental fat excess. This relatively easy technique is described, using a few clinical examples. Indications in maxillo facial surgery are the correction of "double chin" deformity and increased submental fullness after orthognathic surgical procedures as mandibular setback, as well as an adjunct to rhytidectomy. PMID- 1462891 TI - [Role of arthrography in imaging of the temporomandibular joint in 1992]. AB - In this text we briefly want to discuss the role of the arthrographic examination of the temporomandibular joint for detection of disc pathology. We will mention the normal anatomy and function of the temporomandibular joint, the technique for performing arthrograms and the classification of the most frequent disc pathology. This will be illustrated by some arthrographic examples of anterior disc displacement without reduction, disc perforation, and medial disc displacement. Finally the advantages of arthrography in comparison with other investigation techniques will be discussed. PMID- 1462892 TI - Bilateral maxillary and mandibular fourth molars. Report of a case. AB - Fourth molar do not occur very frequently. They tend to be unerupted or if they erupt may cause malalignment of the dentition or aesthetic problems. The preferred location is in the maxilla, and they may be normal or rudimentary and located either directly distal or distolingually to the maxillary third molar. Supernumerary molars should probably be extracted only when their presence is responsible for the failure of eruption or malalignment of permanent teeth. PMID- 1462893 TI - Direct angioplasty versus initial thrombolytic therapy for acute myocardial infarction: long-term follow-up and changes in practice pattern. AB - We retrospectively studied the outcomes of patients with acute myocardial infarction who were treated with either direct angioplasty or thrombolytics followed by angioplasty. Two patient cohorts were analyzed: a previously reported (in regard to short-term follow-up) group of 371 patients who now have long-term follow-up (mean, 3.4 years) of survival and event-free survival and a second group of 202 patients who have been treated since publication of our initial data. Both 1-year and 2-year survival were significantly better (p = 0.01 and 0.02, respectively) in the group that was treated with thrombolytics first. Event free survival (i.e., no myocardial infarction, coronary artery bypass graft surgery, repeat angioplasty) was better overall (p < 0.01) for the group that was treated with thrombolytics first. The more recently treated group of patients also showed benefit in regard to both survival (p = 0.002) and event-free survival (p < 0.01) over a short-term follow-up period (mean, 39 weeks) for patients who were treated initially with thrombolytics as compared with those who were treated with direct angioplasty. Although the initial cohort was very similar to the treatment groups except for age (mean age for the direct angioplasty group was 62 +/- 12 years vs 57 +/- 11 years for thrombolytics first group, (p = 0.0002), several differences existed in the more recent treatment groups. The patients who were more recently treated with direct angioplasty were older, had lower mean ejection fraction, had more extensive coronary artery disease, and were more likely to have had prior coronary artery bypass grafting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462894 TI - Thrombolysis with recombinant human tissue-type plasminogen activator during instability in coronary artery disease: effect on myocardial ischemia and need for coronary revascularization. TRIC Study Group. AB - Two hundred five men, 40 to 70 years of age, admitted to the coronary care unit with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarction), were randomized to double-blind placebo-controlled treatment with an intravenous infusion of recombinant tissue-type plasminogen activator (rTPA), 1 mg/kg body weight (maximum 100 mg) during 4 hours, in addition to aspirin, heparin, and beta-blockade. No severe complications occurred. Myocardial ischemia, defined as myocardial infarction, incapacitating angina despite medication, or signs of ischemia at the exercise test, was reduced by treatment with rTPA compared with placebo both at discharge, 53% compared with 70% (p = 0.02), and at 1 month, 61% compared with 80% (p = 0.005). Signs of myocardial ischemia during the exercise test were reduced at discharge 51.0% compared with 68% (p = 0.03) and at 1 month 48% compared with 62% (p = 0.09). Coronary angiography after 1 month showed no difference in major coronary lesions between the groups, nor was there any reduction in the number of performed coronary revascularization procedures. In conclusion, treatment with rTPA in unstable coronary artery disease in men reduced myocardial ischemia but did not significantly reduce the need for revascularization in long-term follow-up. PMID- 1462895 TI - Outcome of urgent percutaneous transluminal coronary angioplasty in acute myocardial infarction: comparison of single-vessel versus multivessel coronary artery disease. AB - Despite recent clinical trials of percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction, specific groups of patients that may benefit from adjunctive or alternative therapy have yet to be adequately characterized. The in-hospital outcome of 151 consecutive patients treated for acute myocardial infarction with urgent PTCA of the infarct-related artery was studied to identify a subgroup of patients at high risk. Patients were divided into two groups based on the angiographic presence of either single-vessel (n = 86) or multivessel (n = 65) coronary artery disease. Despite PTCA of only the infarct-related artery and similar baseline clinical characteristics such as age, peak serum creatine kinase concentration, left ventricular ejection fraction, and time from the onset of chest pain to arrival at the hospital, the group with multivessel disease had a lower rate of successful angioplasty (75% vs 92%, p < 0.005), with higher incidences of persistent total occlusion of the infarct related artery (14% vs 3%, p < 0.02) and procedural complications during PTCA (28% vs 13%, p < or = 0.02), and were more likely to have multiple complications (12% vs 1%, p < 0.004). In addition, the group with multivessel disease had a higher rate of urgent (< or = 24 hours) coronary artery bypass graft surgery (13% vs 2%, p < 0.05) and a trend toward a higher in-hospital mortality rate (6% vs 1%, p < or = 0.17). By stepwise logistic regression, only the presence of single vessel versus multivessel disease was predictive of PTCA success (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462896 TI - Calcitonin gene-related peptide in patients with and without early reperfusion after acute myocardial infarction. AB - Plasma concentrations of calcitonin gene-related peptide (CGRP), a potent regulator of vascular tone, creatine kinase, myoglobin, and cardiac troponin T were assessed in 31 patients with acute myocardial infarction. In patients who had sustained acute myocardial infarctions, maximum CGRP concentrations (median, 3.2 pmol/L; interquartile range, 1.5 to 4.8 pmol/L) were markedly elevated as compared with healthy control subjects (n = 23; median, 1.02 pmol/L; p = 0.02). However, no marked differences in CGRP levels were observed between patients with early reperfusion (n = 19; median, 3.5 pmol/L) and patients without early reperfusion (n = 12; median, 2.6 pmol/L; p = 0.96), as well as between those with congestive heart failure (n = 8; median, 3.9 pmol/L) and those without congestive heart failure (n = 23; median, 3.2 pmol/L; p = 0.62). CGRP did not correlate closely with myocardial protein release or hemodynamic parameters (heart rate and blood pressure) or the occurrence of arrhythmias. Therefore we conclude that elevated peripheral venous CGRP concentrations in patients who have sustained an acute myocardial infarction are independent of successful reperfusion and hemodynamic state. Although the cause of CGRP increase is not yet identified, CGRP may play a role in the regulation of coronary vascular tone in patients after acute myocardial infarction. PMID- 1462898 TI - Inosine--a natural modulator of contractility and myocardial blood flow in the ischemic heart? AB - The energetic role of inosine (INO) remains controversial. The aim of the present study was first to test whether endogenous INO consumption/production correlates with regional myocardial contractile performance and second to test whether locally increased levels of INO influence contractility and blood flow in severely ischemic myocardium. Fentanyl-anesthetized dogs with implanted sonomicrometry crystals and independently perfused left anterior descending coronary arteries were studied. Two relatively load-independent indexes of regional myocardial contractility derived from left ventricular pressure-segment length loops were used: the regional stroke work-end-diastolic segment length relationship (Wr/L(ed)) and the end-systolic pressure-segment length relationship (Plv/L(es)). Very good correlations between myocardial contractile performance (as measured by the slope of the regional Wr/L(ed) relationship) and endogenous INO consumption/production under both nonischemic and ischemic conditions were found. Ischemia severely depressed contractility, significantly shifting rightward the Wr/L(ed) and Plv/L(es) relationships. INO infused into the left anterior descending bypass, in a concentration of 600 to 800 mumol/L, partially restored contractile performance as evidenced by a significant leftward displacement of both relationships. Wr, measured at a common maximum L(ed), increased significantly by 61 +/- 5%. Border-zone collateral flow (microspheres) increased by 35 +/- 7% within the endocardial segments and by 34 +/- 9% in the epicardial segments, but no increase in flow in the ischemic region was measureable. With the current emphasis on recanalization with thrombolytic therapy and considering the apparent safety of INO, this naturally occurring nucleoside might prove to be a useful adjunctive agent in the treatment of acute myocardial ischemia. PMID- 1462897 TI - Adenosine is an endogenous protectant against stunning during repetitive ischemic episodes in the heart. AB - To investigate whether adenosine receptor blockade alters the response to serial coronary occlusions in the rabbit heart, we measured changes in segment length with ultrasonic dimension gauges placed in the field of a coronary branch. The coronary branch was subjected to four 5-minute occlusions, each separated by 10 minutes of reperfusion. In control hearts, the percentage of segment shortening fell from 15.7% to 9.3% after release of the first occlusion with no further deterioration after each of the subsequent three occlusions. In hearts in which adenosine receptors were blocked with PD 115,199, a potent blocker of both A1 and A2 receptors, segment shortening again recovered to about two thirds of the preischemic value during the reperfusion period after the first occlusion. Each subsequent occlusion, however, resulted in a further deterioration of function to the extent that shortening was less than 20% of the preischemic value during reperfusion after the fourth occlusion. Therefore the first occlusion of a series of four occlusions, while mildly stunning the heart, also preconditions the myocardium against further stunning by subsequent occlusions. Because that protection was when adenosine receptors were blocked, adenosine must play an important role in the mediation of this protective effect. PMID- 1462899 TI - Comparison of acute elastic recoil after directional coronary atherectomy versus standard balloon angioplasty. AB - We evaluated intraprocedural "elastic recoil" in 25 patients (22 men and 3 women) undergoing directional coronary atherectomy (DCA) of left anterior descending stenoses, and compared these with 25 temporally-matched (14 men and 11 women) patients having balloon angioplasties (PTCA). Quantitative arteriography was performed using the Coronary Measurement System (Leiden, The Netherlands), with "elastic recoil" defined as the difference in maximum device or balloon size minus residual minimum diameter. In addition, we determined the effects of relative device size, specific anatomic location (proximal/mid artery), lesion length, eccentricity (symmetry index), and dystrophic calcification on acute "recoil" severity after both procedures. Although initial coronary stenoses were similar (minimum stenotic diameter, DCA = 0.59 +/- 0.20 mm versus PTCA = 0.55 +/- 0.23 mm, p = NS), less "elastic recoil" was observed after atherectomy (DCA = 0.83 +/- 0.57 mm versus PTCA = 1.26 +/- 0.56 mm, p < 0.01), and this was confirmed by absolute recoil/maximum device size ratios (DCA = 23.5 +/- 16.0% versus PTCA = 41.6 +/- 13.8%, p < 0.01). Acute "elastic recoil" was also influenced by maximum device size/"normal" coronary artery ratios [(ratio < 0.9, DCA = 0.26 +/- 0.10 mm versus PTCA = 0.84 +/- 0.13 mm, p < 0.01); (ratio 0.9 to 1.1, DCA = 0.69 +/- 0.41 mm versus PTCA 0.75 +/- 0.32 mm, p = NS); (ratio > 1.1, DCA = 1.09 +/- 0.64 mm versus PTCA = 1.59 +/- 0.48 mm, p < 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462900 TI - Percutaneous angioscopic evaluation of luminal changes induced by excimer laser angioplasty. AB - Angioscopy has been shown to provide more detailed information on lesion morphology before and after interventional procedures than angiography. Therefore to evaluate the effects of laser angioplasty, angioscopy was performed in five patients with peripheral or coronary vascular disease who underwent excimer laser angioplasty. The excimer laser was operated at 308 nm, 135 nsec, 25 Hz, and 40 to 60 mjoules/mm2 and was coupled into multifiber wire-guided catheters of 1.4 to 2.0 mm diameter for coronary lesions and into catheters of 2.2 mm diameter for peripheral lesions. There were three coronary (one left anterior descending, one circumflex, one right coronary artery) and two peripheral (one common iliac artery, one superficial femoral artery) lesions. Angioscopy was successfully performed before and after laser ablation without any complications in all five lesions. The characteristics of angioscopic findings after excimer laser angioplasty consisted of flaps, fractures of plaques, and abundant tissue remnants. There was no apparent thermal injury. Recanalized channels were small and irregular. These results indicate that (1) angioscopy is effective and safe for evaluation of lesion morphology after laser angioplasty; (2) laser ablation does not result in thermal injury; and (3) irregular channels after recanalization and abundant tissue remnants may explain the suboptimal results after laser angioplasty. PMID- 1462901 TI - Angiographic restenosis after successful Wallstent stent implantation: an analysis of risk predictors. AB - Follow-up angiographic study was performed in 86 patients after initially successful Wallstent stent (Medinvent, Lausanne, Switzerland) implantation between April 1986 and October 1990. The stent angiographic restenosis rate was 16% at a mean of 8 months after stenting despite the inclusion of a substantial number of patients at high risk of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Of a total 15 variables analyzed, only suboptimal stent placement was found to be a significant predictor of stent restenosis. Age; gender; baseline New York Heart Association functional class; previous PTCA; indication for stenting; left ventricular ejection fraction; preangioplasty and immediate postangioplasty diameter stenosis severity; stented vessel site, lesional morphology; number, diameter, and length of stents implanted; and the interval between stenting and follow-up angiographic restudy were not significant risk factors of stent restenosis. Our study suggests that intracoronary stent implantation with the Wallstent may be a useful and promising adjunctive option after PTCA, particularly in patients at high risk of restenosis after PTCA. However, because of the significantly enhanced risk of restenosis after suboptimal stent implantation, we strongly recommend the selection and placement of Wallstent stents that adequately cover the entire length of the dilated coronary segment. PMID- 1462902 TI - Lidocaine to prevent ventricular fibrillation in the prehospital phase of suspected acute myocardial infarction: the North-Norwegian Lidocaine Intervention Trial. AB - The efficacy of lidocaine to prevent ventricular fibrillation during the prehospital phase of suspected acute myocardial infarction was assessed 3 hours after administration in a randomized controlled trial. A total of 204 patients examined within 6 hours after onset of symptoms were included, and acute myocardial infarction was later confirmed in 63% of these. Lidocaine, administered as a 100 mg intravenous bolus dose followed by a 300 mg intramuscular injection, failed to prevent ventricular fibrillation, which was observed in 2 (2.1%) of 96 patients in the lidocaine group and in 3 (3.0%) of 101 patients in the placebo group (p = 0.95; odds ratio 0.7, 95% confidence interval 0.4 to 1.3). In addition, sudden cardiac collapse with unknown heart rhythm was observed in three patients who received lidocaine (3.1%) compared with none in the placebo group (p = 0.23; odds ratio 7.6, 95% confidence interval 2.8 to 22.1). The results of this small study suggest that lidocaine, even when given in a high dose, is ineffective in preventing ventricular fibrillation when administered before hospitalization for suspected acute myocardial infarction. Prophylactic use of lidocaine in this situation may therefore not be warranted or advisable. PMID- 1462903 TI - Determinants of the hemodynamic consequence to sustained ventricular arrhythmias after a single myocardial infarction. AB - Patients who have sustained ventricular arrhythmias after myocardial infarction present with either a cardiac arrest or with hemodynamically stable sustained ventricular tachycardia. Recent reports have suggested a different electrophysiologic milieu in these two patient groups and a higher incidence of cardiac arrest in patients with a history of more than one myocardial infarction. No studies have examined patients with only a single previous myocardial infarction. To assess the determinants of the hemodynamic consequence of sustained ventricular arrhythmias more than 3 days after a single myocardial infarction, 82 patients who were resuscitated from arrhythmic cardiac arrest (CA group, 40 patients) or who had hemodynamically stable sustained ventricular tachycardia (No CA group, 42 patients) were examined. Patients in both groups had similar global left ventricular ejection fractions (mean +/- SD; 30% +/- 12% vs 27% +/- 12%; p = NS), proportion of patients with anterior wall infarctions as compared with the proportion of patients with inferior wall infarctions (55% vs 50%; p = NS), time from infarction to arrhythmia development, severity of coronary artery disease, and the proportion of patients with congestive heart failure or bundle branch block. Patients who presented without cardiac arrest, however, more frequently had left ventricular aneurysms (58% vs 28%; p = 0.005). Sixty-seven patients underwent baseline drug-free electrophysiologic studies. Sustained ventricular tachycardia was induced in 79% of patients in the CA group and 85% of patients in the No CA group (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462905 TI - Outcome of endocardial resection in 33 patients with coronary artery disease: correlation with ventricular tachycardia morphology. AB - The results in 33 patients with ventricular tachycardia (VT) treated by endocardial resection were reviewed, with special emphasis on the presence of single or multiple morphologies preoperatively and intraoperatively. Multiple VT morphologies were induced in 16 patients and a single VT morphology was induced in the remaining 17. Intraoperative programmed stimulation failed to induce VT in eight patients and visually-directed endocardial resection was performed. The remaining patients underwent map-guided resection. The surgical success rate did not correlate with any morphologic characteristics of the VT, such as bundle branch block pattern or axis. In addition, concordance of VT morphologies preoperatively and intraoperatively before resection did not correlate with the surgical success rate. However, patients in whom multiple morphologies of VT were induced intraoperatively had a significantly higher success rate (100%) compared with those patients in whom only a single morphology was induced intraoperatively (50%, p < 0.05). Long-term follow-up was maintained in 26 patients. Ventricular tachycardia recurred in two patients and VF recurred in two others who did not have inducible VT 1 week after endocardial resection. In conclusion, neither the preoperative morphologic characteristics of VT nor discordance between the morphologies of VT induced preoperatively and in the operating room influenced the outcome of endocardial resection. However, the surgical success rate is higher when multiple morphologies of VT are inducible in the operating room than when only one VT morphology is inducible. PMID- 1462904 TI - Defibrillation electrode configurations developed from cardiac mapping that combine biphasic shocks with sequential timing. AB - Previous canine mapping studies of the transvenous defibrillation lead configuration of right ventricle (RV) to left R2 patch (P) revealed regions of low potential gradient in the left ventricular apex (A) and the right ventricular outflow tract (O). Thus 16 new lead configurations were tested in eight dogs, which incorporated electrodes in A and O to raise the gradient. When used in conjunction with two sequential biphasic shocks, the average defibrillation threshold energy from these configurations was 57% lower than that produced by a single biphasic shock delivered through RV-->P (phase 1 cathode-->anode, p < 0.001). Of the 16 configurations tested, the most effective was RV-->P followed by A-->O. When the shocking order of this configuration was reversed in another eight dogs, no difference in defibrillation efficacy was noted. In individual configurations of RV-->P and A-->O that used a single biphasic shock, defibrillation was not effective. Finally, when two sequential biphasic shocks were delivered to the same two electrodes in seven other dogs, the defibrillation efficacy was low. Thus configurations that use two sequential biphasic shocks can produce low defibrillation thresholds when the shocks are delivered to two different sets of electrodes. The high efficacy may be caused by one shock increasing the potential gradient in regions of low potential gradient that are produced by the other shock. PMID- 1462906 TI - Irregular ventricular tachycardia: a possible manifestation of longitudinal dissociation within the reentry pathway. AB - Sustained monomorphic ventricular tachycardia is usually regular; that is, it is associated with constant R-R intervals. In several cases, however, the cycles of ventricular tachycardia are more or less variable. Fifty-four cases of sustained monomorphic ventricular tachycardia were evaluated in order to assess whether tachycardia was regular. Nine cases were defined as irregular (i.e., the R-R cycles varied by more than 40 msec throughout a 1-minute recording). In five cases tachycardia was "regularly irregular," since the R-R cycles could be divided into two separate groups: the group of long cycles and that of short cycles. In these cases the variability manifested according to a defined and constant pattern: bigeminal pattern (alternation of short and long cycles), trigeminal pattern (two short cycles followed by a long cycle), and so on. The regular variability of tachycardia cycle length suggests one of the following possibilities. (1) There are two alternative circuits (a short circuit and a long circuit) that share the same exit pathway. Whenever the reciprocating impulse runs through the short circuit, the R-R cycle is short; but if a block in the short circuit occurs, the impulse runs through the long circuit, resulting in a long R-R cycle. (2) There is a longitudinal dissociation within the reentry circuit; two separate pathways with different inherent conduction velocities are present. When the impulse runs through the fast pathway, the R-R cycle is short; whereas when a block in the fast pathway occurs, the impulse traverses the slow pathway, resulting in a long R-R cycle. PMID- 1462907 TI - Reversibility of left ventricular dysfunction after successful catheter ablation of supraventricular reentrant tachycardia. AB - Fourteen patients (mean age, 48 +/- 19 years) with left ventricular dysfunction in the absence of underlying organic heart disease underwent catheter ablation (nine with direct-current energy and five with radiofrequency energy) to treat drug-refractory, symptomatic supraventricular reentrant tachycardia (mean duration of tachycardia, 22 +/- 17 years). Clinical tachycardias were accessory pathway-mediated tachyarrhythmia (12 patients) and atrioventricular nodal reentrant tachycardia (two patients). Changes of ventricular function after successful ablation, as assessed by radionuclide ventriculography and echocardiography, showed a decrease in left ventricular end-systolic dimension (39 +/- 6 mm to 34 +/- 6 mm; 32 +/- 6 mm; p < 0.05) and in left ventricular end diastolic dimension (55 +/- 5 mm to 52 +/- 3 mm; 51 +/- 3 mm; p < 0.05) in the early (2 to 3 months) and late (6 to 8 months) follow-up periods, increase of nuclear ejection fraction (38% +/- 8% to 46% +/- 7%; p < 0.05) and fractional shortening (28% +/- 7% to 36% +/- 8%; p < 0.05) in the late follow-up period. Increase of fractional shortening was mainly due to decrease in the end-systolic dimension. These findings suggest that prolonged attacks of uncontrolled supraventricular tachycardia may result in left ventricular dysfunction, which is reversible after successful catheter ablation of the arrhythmias. PMID- 1462908 TI - Noninvasive assessment of systolic and diastolic left ventricular function in patients with chronic severe anemia: a combined M-mode, two-dimensional, and Doppler echocardiographic study. AB - Thirty-one patients with chronic severe anemia of more than 3 months' duration (hemoglobin less than 7 gm/dl) and no underlying heart disease were studied by means of M-mode, two-dimensional, and Doppler echocardiography; an equal number of normal control subjects was also studied. There are conflicting reports regarding the influence of chronic severe anemia on systolic myocardial function, but diastolic function has not been systematically assessed. It is also uncertain whether anemia alone can cause heart failure in a structurally normal heart. We therefore performed a detailed study of echocardiographic indexes of systolic and diastolic left ventricular function in these patients. We found that patients with anemia have significantly faster heart rates and lower diastolic and mean blood pressures than normal subjects. They also have a significantly elevated cardiac output and stroke volume and larger left ventricles. Left ventricular contractility, assessed by the end-systolic stress-dimension relationship, was enhanced. There was no systematic evidence of diastolic dysfunction by Doppler assessment of mitral inflow. There was also no clinical evidence of congestive heart failure. We conclude that chronic severe anemia leads to a hyperdynamic state with systolic hyperfunction and no impairment of diastolic function. Anemia does not lead to congestive heart failure in the absence of underlying heart disease. PMID- 1462909 TI - Prognostic significance of Doppler-derived left ventricular diastolic filling variables in dilated cardiomyopathy. AB - To determine the prognostic significance of pulsed wave Doppler-derived left ventricular diastolic filling velocity profiles and the relationship between Doppler variables and clinical functional status, the follow-up outcomes of 62 consecutive patients with dilated cardiomyopathy and symptoms of left ventricular dysfunction were analyzed. All patients had echocardiographic left ventricular end-diastolic dimension > or = 6.0 cm, fractional shortening < 25%, increased E pointseptal separation, and diffuse hypokinesia or akinesia. During a mean follow up period of 30.5 +/- 13.9 months, 27 patients experienced cardiac events: 23 died of either progressive pump failure or an episode of sudden death and four required cardiac transplantation because of refractory heart failure. Peak early filling velocity (78 +/- 23 cm/sec vs 65 +/- 25 cm/sec; p < 0.03) was higher and late atrial filing velocity (34 +/- 13 cm/sec vs 55 +/- 19 cm/sec; p < 0.001) was lower in patients with cardiac events than in cardiac event-free survivors. The ratio of early to late transmitral filling velocities was higher (2.6 +/- 1.2 vs 1.5 +/- 1.3; p < 0.001), and the deceleration time of early diastole was shorter (133 +/- 48 msec vs 175 +/- 71 msec; p < 0.001) in patients with cardiac events. The cardiac event rate was significantly higher in patients with an early to late filling velocity ratio greater than 2 (77% vs 19%; p < 0.001) or a deceleration time less than 150 msec (58% vs 23%; p < 0.05) than in those without. Stepwise multivariate regression analysis revealed that the pattern of transmitral early to late filling velocity ratio was the only significant independent Doppler echocardiographic predictor of outcome for these patients. Repeat Doppler echocardiographic examinations, which were performed in 31 survivors after intensive treatment (mean, 38.6 +/- 6.5 months), showed that early filling velocity was decreased (55 +/- 20 cm/sec vs 75 +/- 25 cm/sec; p < 0.02), late atrial filling velocity was increased (74 +/- 27 cm/sec vs 57 +/- 21 cm/sec; p < 0.01), early to late filling velocity ratio was reduced (0.8 +/- 0.3 vs 1.7 +/- 1.3; p < 0.001), and deceleration time was prolonged (227 +/- 60 msec vs 167 +/- 82 msec; p < 0.01) in 18 patients with clinical functional improvement, whereas these measurements were unaltered in the remaining 13 patients whose functional status was unchanged or had deteriorated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1462910 TI - Mild dehydration induces echocardiographic signs of mitral valve prolapse in healthy females with prior normal cardiac findings. AB - This study was designed to investigate the hypothesis that mitral valve prolapse (MVP) can be induced after diuresis in women without the abnormality who have characteristic body habitus. Fifteen tall, slim, healthy female volunteers with a normal cardiac findings, echocardiogram, and history were investigated after mild diuresis with furosemide and after placebo. All subjects lost weight after furosemide and placebo administration; but mean weight loss was significantly greater after furosemide administration than after placebo administration. Echocardiography showed MVP in none of the 15 patients before treatment, in seven after administration of placebo, and in seven after administration of furosemide. Coaptation point prolapsed superior to the anulus in seven subjects with echocardiographically determined MVP. Left ventricular end-diastolic dimensions decreased significantly after placebo or furosemide administration in subjects in whom MVP developed compared with the measurement in those in whom MVP did not develop. Murmurs characteristic of MVP disappeared in all four rehydrated subjects and echocardiographic changes resolved in two of the five rehydrated subjects. Thus echocardiographically determined MVP can be induced by mild dehydration in women with phenotypic body habitus of MVP; changes may resolve with rehydration. Results suggest an explanation for variable physical examination findings in persons with MVP. PMID- 1462911 TI - Prospective study of blood culture during transesophageal echocardiography. AB - To ascertain the incidence and significance of bacteremia associated with transesophageal echocardiography (TEE), 132 consecutive patients (aged 17 to 73 years) free of apparent infection who were undergoing 135 transesophageal echocardiographic procedures from October 1990 to August 1991, were prospectively studied. For each procedure, two sets of blood cultures were obtained for culture 30 to 60 minutes before TEE, immediately after, and 180 to 240 minutes after the procedure. For each blood culture, 10 ml of venous blood was evenly inoculated into aerobic and anaerobic culture bottles and inoculated for 7 days using a radiometric system. A throat swab was obtained immediately before each procedure. Three of 270 preprocedure blood cultures were positive for Bacillus cereus, Staphylococcus simulans, and Peptostreptococcus species, respectively. No blood culture was positive in the immediate postprocedure period. Two of 270 late blood samples grew Staphylococcus epidermidis in the same patient. Nevertheless, the microorganisms isolated from blood cultures were different from those isolated from the throat swab. No patients had fever or evidence of infective endocarditis after TEE during the follow-up period. It is concluded that the incidence of TEE related bacteremia is extremely low, and a general recommendation for antibiotic prophylaxis during TEE is not warranted. PMID- 1462912 TI - Transesophageal contrast echocardiography and color flow mapping: methods of choice for the detection of shunts at the atrial level? AB - The detection of shunts at the atrial level is important, and a reliable means of diagnosis is required. Precordial contrast echocardiography is usually performed to detect such shunts. To investigate the advantages of transesophageal echocardiographic techniques, we studied 167 consecutive patients with both precordial and transesophageal echocardiography, using two-dimensional imaging with contrast techniques (with and without a Valsalva maneuver) and color flow mapping. A patent foramen ovale was diagnosed in 31 patients, an atrial septal defect in 11 (7 with bidirectional shunts), and a pulmonary arteriovenous fistula in 3 patients. All right-to-left shunts were detected with transesophageal contrast echocardiography. With these results used as the gold standard, the sensitivity of combined precordial techniques was 37% and that of transesophageal color flow mapping 46%. All left-to-right shunts were detected by transesophageal color flow mapping. With these results used as the gold standard, the sensitivities of both precordial color flow mapping and a transesophageal negative right atrial contrast study were 27%. We conclude that transesophageal contrast echocardiography is the echocardiographic method of choice for the detection of a right-to-left shunt at the atrial level, which cannot be excluded by negative results on precordial study or on transesophageal color flow map study. A left-to-right shunt at this level is best detected by transesophageal color flow mapping. PMID- 1462913 TI - Late death after arterial switch operation for transposition of the great arteries. AB - Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average. PMID- 1462914 TI - Balloon valvotomy for pregnant patients with severe pliable mitral stenosis using the Inoue technique with total abdominal and pelvic shielding. AB - Balloon valvotomy by means of the Inoue technique was attempted in seven pregnant (5 to 9 months) patients with severe mitral stenosis; the mean age of the patients was 32 +/- 8 years, and all had a two-dimensional echocardiographic mitral valve score of < 8. Indications for Inoue balloon valvotomy included severe symptomatic mitral stenosis with a Doppler mitral valve area < or = 1 cm2 and heart failure refractory to medical therapy, or absolute contraindications for the use of beta-blockade; Inoue valvotomy was also indicated for patients who lived a long distance from the hospital. Inoue balloon valvotomy was performed with no angiography and total pelvic and abdominal shielding; the balloon catheter was introduced into the right atrium without the aid of fluoroscopy, which was used for the transseptal puncture. Stepwise two-dimensional echocardiographic Doppler mitral valve dilatation was done. After Inoue balloon valvotomy the mean Doppler mitral valve area increased from 0.8 +/- 0.1 to 2.0 +/ 0.3 cm2 (p < 0.01) and by two-dimensional echocardiography from 0.8 +/- 0.2 to 1.9 +/- 0.3 cm2 (p < 0.01), with no significant Doppler residual stenosis (defined as mitral valve area < or = 1.5 cm2). The mean total fluoroscopy time was 16 +/- 7 minutes. The degree of mitral regurgitation increased in two patients from grade 1+/4+ to grade 2+/4+ and from grade 0+/4+ to grade 2+/4+, respectively. There was no mortality or significant morbidity. Pregnancy was uneventful in all patients, and all were delivered of normal babies without complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462915 TI - Percutaneous mitral balloon valvuloplasty--a comparative evaluation of two transatrial techniques. AB - The efficacy and safety of two different percutaneous transfemoral mitral balloon valvuloplasty procedures were evaluated in 45 patients. A double-balloon technique with Mansfield balloons was applied in the first 22 patients (group A), and an Inoue single-balloon technique was used in the subsequent 23 patients (group B). Mean diastolic gradient decreased from 17 +/- 7 mm Hg to 8 +/- 3 mm Hg (p < 0.001) in group A and from 13 +/- 4 mm Hg to 8 +/- 3 mm Hg (p < 0.001) in group B. The mitral orifice area increased from 1.1 +/- 0.3 cm2 to 2.2 +/- 0.8 cm2 (p < 0.001) in group A and from 1.2 +/- 0.4 cm2 to 1.7 +/- 0.7 cm2 (p < 0.001) in group B. The length of the total procedure and the total fluoroscopy time were considerably shorter in group B (86 +/- 24 minutes and 18 +/- 7 minutes) compared with group A (128 +/- 38 minutes and 35 +/- 14 minutes; p < 0.001). Mitral regurgitation (grade 3/4) was observed after the procedure in two patients in group A but in nine patients in group B. Cardiac tamponade occurred in two patients in group A, but no major complications were seen in group B. The Inoue single-balloon technique seemed to be safe, easier to perform, and equally effective. PMID- 1462916 TI - The effect of aspirin on the risk of stroke in patients with nonrheumatic atrial fibrillation: The BAATAF Study. AB - Recent randomized trials have consistently demonstrated the marked efficacy of warfarin in reducing the risk of stroke caused by nonrheumatic atrial fibrillation. These trials have provided conflicting evidence on the effect of aspirin. We report the aspirin analysis from the BAATAF study, a trial in which control patients could choose to take aspirin. There we two strokes in 446 person years with warfarin (annual rate of 0.45%); eight strokes in 206 person-years with aspirin, most at 325 mg per day (annual rate of 3.9%); and five strokes in 271 person-years among patients taking neither aspirin nor warfarin (annual rate of 1.8%). Simultaneously controlling for the other significant determinants of stroke in the BAATAF study (age, mitral annular calcification, and clinical heart disease), the relative rates (95% confidence interval) of stroke were: (1) warfarin/aspirin = 0.135 (0.029 to 0.64); (2) aspirin/(no aspirin and no warfarin) = 1.95 (0.64 to 5.97); and (3) warfarin/(no aspirin and no warfarin) = 0.263 (0.051 to 1.36). Our "treatment received" analysis argues that warfarin is strikingly more effective than aspirin in preventing stroke in nonrheumatic atrial fibrillation. PMID- 1462917 TI - Comparison of withdrawing antihypertensive therapy between diuretics and angiotensin converting enzyme inhibitors in essential hypertensives. AB - One hundred thirteen patients with essential hypertension receiving single or multiple antihypertensive agents were enrolled in the study. All had had mild to severe hypertension before treatment, but their diastolic blood pressure (DBP) at study entry was lower than 90 mm Hg for all measurements. In half of the subjects, non-thiazide diuretics (n = 35) or angiotensin-converting enzyme inhibitors (ACEI, n = 37) were discontinued, and their remaining drugs were maintained throughout the study. The other patients (n = 41) continued all their medications. Forty-one percent of subjects remained normotensive for 12 months after withdrawal of diuretics, and 37% of patients with ACEI discontinuation remained normotensive, although the recurrence of hypertension after withdrawal of ACEI tended to be earlier than its recurrence after withdrawal of diuretics. Serum uric acid and creatinine concentration decreased after diuretic withdrawal, but not after ACEI withdrawal. Diuretic withdrawal resulted in an increase in serum potassium, but ACEI withdrawal induced a decrease in serum potassium. Withdrawal of diuretics or ACEI both significantly reduced plasma renin activity. The present study may be indicative of the ability to withdraw some medications in many patients being treated with multiple antihypertensive agents. PMID- 1462918 TI - The treadmill exercise score revisited: coronary arteriographic and thallium perfusion correlates. AB - The treadmill exercise score has been used to stratify patients into low-, moderate-, and high-risk groups. This score is derived from ST segment depression, angina, and exercise duration. To determine the coronary arteriographic and exercise thallium perfusion correlates of the score, we examined the extent of coronary artery disease and exercise single photon emission computed thallium-201 results in 834 patients for whom cardiac catheterization data were available. Of those, 174 had no coronary artery disease, 195 had one-vessel, 246 had two-vessel, and 219 had three-vessel disease. Based on the treadmill exercise score, 369 were in the low-risk, 384 in the moderate-risk, and 81 in the high-risk group. The extent of coronary artery disease was 2.1 +/- 1 diseased vessels in the high-risk, 1.7 +/- 1 in the moderate, and 1.4 +/- 1.1 in the low-risk group (p < 0.01). The extent of the thallium abnormality (maximum number of abnormal segments 120/patient) was 10 +/- 6 in the high-risk, 7 +/- 6 in the moderate, and 6 +/- 5 in the low-risk group (p < 0.05). Based on the extent of coronary artery disease and results of thallium imaging, patients were reclassified into three groups: group 1 had three-vessel disease and/or > or = 10 abnormal segments (n = 387), group 3 had no coronary artery disease or one-vessel disease and less than five abnormal segments (n = 212), and the remaining patients were in group 2 (n = 235).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462919 TI - Radiation-induced coronary artery disease. AB - Excessive unprotected radiation to the heart appears to lead to the development of CAD, even in the absence of significant cardiovascular risk factors. The coexistence of such factors may enhance the probability of CAD. The presence of hypercholesterolemia and concomitant or sequential use of chemotherapeutic agents (especially doxorubicin) could further increase this risk. Therapeutic decisions, as with any other manifestation of CAD, relate to the extent of myocardium at jeopardy and to the overall diffuseness of CAD. Management options possible are PTCA or coronary artery bypass surgery. The latter may be required in left main artery stenosis and complicated ostial lesions. Use of shielding should decrease the associated risk of radiation-induced CAD in future years. However, clinicians should continue to have a high degree of suspicion of CAD in patients treated with thoracic radiation without cardiac shielding. PMID- 1462920 TI - Single photon emission computed tomographic teboroxime imaging with a preprocessing masking technique. AB - We previously reported that single-head SPECT imaging with teboroxime is feasible. However, excessive hepatic uptake in some patients may interfere with image interpretation. This study examined the feasibility of improving image quality by use of a preprocessing masking technique to subtract hepatic activity. A band of 10 pixels in width adjacent to the inferior cardiac silhouette was marked on the raw planar images, and then SPECT reconstruction was done with the Butterworth filter with a frequency cutoff of 0.3 cycles/cm and the power of 10. The stress and rest images were compared before and after masking in 10 patients who underwent SPECT teboroxime imaging during adenosine-induced coronary hyperemia (140 micrograms/kg/min for 6 minutes). SPECT imaging with a single-head detector was performed with the use of a 180-degree anterior arc (from the 45 degree left posterior oblique projection to the 45-degree right anterior oblique projection); 32 images at 8 seconds per stop were obtained (total imaging time = 6.8 minutes). All images were considered subjectively better after the masking technique was used, especially for assessment of inferior wall perfusion pattern. The maximum count in any pixel was in the hepatic region of interest before masking and in the cardiac region of interest after masking (303 +/- 110 counts vs 166 +/- 55 counts; p < 0.001). The difference was especially pronounced in the images that were obtained when patients were at rest (366 +/- 102 counts vs 184 +/- 64 counts; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462921 TI - Survival of implantable cardioverter-defibrillator recipients: role of left ventricular function and its relationship to device use. AB - The quantitative benefit of ICD therapy in patients with malignant ventricular tachyarrhythmia with different degrees of left ventricular dysfunction is unclear. We evaluated patterns of ICD use and survival in 112 patients with moderate to severe left ventricular dysfunction. Group 1 included 57 patients with moderate left ventricular dysfunction (defined as left ventricular ejection fraction greater than 30%) and group 2 comprised 55 patients with severe left ventricular dysfunction (defined as ejection fraction equal to or less than 30%). The follow-up period ranged from 1 to 78 months. Age, incidence of coronary artery disease, and presenting arrhythmia in the two groups were similar. The mean left ventricular ejection fraction in group 1 was 44.6 +/- 8.2% and in group 2 was 21.6 +/- 6% (p < 0.0001). At 3 years of follow-up 65% of the patients in group 1 and 71% in group 2 (p = NS) had ICD activation for presumed ventricular tachycardia. Survival was calculated by means of actuarial analysis. Arrhythmia or sudden death mortality at 4 years of follow-up was 5% in group 1 and 9% in group 2 (NS). Cardiac mortality was higher in patients with severe left ventricular dysfunction reaching levels of statistical significance at 2 years of follow-up. At 2 years of follow-up it was 12% in group 1 and 40% in group 2 (p = 0.05), and at 4 years of follow-up it was 15% in group 1 and 43% in group 2 (p < 0.01). In both groups there was no difference in cardiac mortality in patients who did and did not have appropriate ICD shocks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462922 TI - Flecainide acetate for treatment of tachyarrhythmias in children: review of world literature on efficacy, safety, and dosing. AB - A review of all published experience with flecainide in infants, children, and fetuses was performed to evaluate the appropriate place of the drug in pediatric practice and to determine dosing guidelines. A total of 704 case references was generated. Flecainide appeared to be safe (no deaths with usual oral dosing, < 1% serious proarrhythmia) and effective (73% to 100% control, depending on mechanism) in children with supraventricular tachycardia. The drug was very effective for treatment of fetal tachyarrhythmias. Flecainide may not be safe for children who have structurally abnormal hearts and atrial flutter or ventricular arrhythmias. The safety of flecainide for patients with ventricular arrhythmias and normal hearts requires further investigation. Pharmacokinetic data reveal an age-dependent change in elimination half-life. Patients younger than 1 year of age have a plasma elimination half-life that is similar to that in children older than 12 years (i.e., 11 to 12 hours). Children aged 1 to 12 years have a mean elimination half-life of 8 hours. The effective flecainide dose is 100 to 200 mg/m2/day or 1 to 8 mg/kg/day. Toxicity may occur with doses in excess of these ranges, especially when high doses are accompanied by low serum trough levels. Milk blocks flecainide absorption, and toxicity may become manifest when milk products are removed from the diet. PMID- 1462923 TI - Transumbilical balloon coarctation angioplasty in neonates with critical aortic coarctation. PMID- 1462924 TI - Transcatheter coil embolization of a fistula from the posterior descending coronary artery to the right ventricle in a two-year-old child. PMID- 1462925 TI - Apical hypertrophic cardiomyopathy of the Japanese type: occurrence with familial hypertrophic cardiomyopathy in a family. PMID- 1462926 TI - Cardiac amyloidosis detected by indium-111 antimyosin imaging. PMID- 1462927 TI - QRST isointegral maps in patients with Romano-Ward syndrome. PMID- 1462928 TI - Fatal posttraumatic cardiac causalgia. PMID- 1462929 TI - Delayed and spontaneous coronary artery rupture following nonpenetrating chest trauma. PMID- 1462931 TI - Reversibility of cocaine-induced cardiomyopathy. PMID- 1462930 TI - Asymptomatic pseudoaneurysm of the left ventricle and coronary artery fistula after closed-chest ablation of an accessory pathway. PMID- 1462932 TI - Dissecting intramyocardial hematoma presenting as a massive pseudotumor of the right ventricle. PMID- 1462933 TI - Fatal pulmonary venoocclusive disease after use of oral contraceptives. PMID- 1462934 TI - The effects of epicardial coronary spasm on intracoronary flow velocity and pressure gradient in a patient after cardiac transplantation. PMID- 1462935 TI - Emergency recognition and treatment of strut fracture and disc embolization in patients with Bjork-Shiley valve prosthesis. PMID- 1462936 TI - Transesophageal echocardiographic detection of atrial wall aneurysm as a result of abnormal attachment of mitral prosthesis. PMID- 1462937 TI - Accelerated calcification of an aortic bioprosthesis in an octogenarian. PMID- 1462938 TI - Application of a new real-time temperature control pulsed laser for ablation of atherosclerotic plaque. PMID- 1462939 TI - Identification of coronary sinus septal defect (unroofed coronary sinus) by color Doppler echocardiography. PMID- 1462940 TI - Transesophageal echocardiographic diagnosis of coronary sinus type atrial septal defect. PMID- 1462941 TI - Aneurysm of the noncoronary sinus of Valsalva ruptured into the left atrium. PMID- 1462942 TI - Sinus node hibernation resolved by PTCA. PMID- 1462943 TI - Balloon valvotomy of mitral bioprosthetic stenosis. PMID- 1462944 TI - Intraaortic atherosclerotic debris by transesophageal echocardiography. PMID- 1462945 TI - Aortic dissection and cocaine use. PMID- 1462946 TI - ST elevation after electroversion of atrial fibrillation. PMID- 1462947 TI - Extraction of transvenous pacing leads. PMID- 1462948 TI - Heparin for left ventricular thrombus. PMID- 1462949 TI - QT interval after myocardial infarction. PMID- 1462950 TI - Counting angels and bacteria. The quest for a unifying theory of ulcerogenesis. PMID- 1462951 TI - Hepatitis delta virus. No longer a defective virus. PMID- 1462952 TI - Evidence that hepatitis D virus needs hepatitis B virus to cause hepatocellular damage. AB - Serial liver biopsy specimens from 11 patients who had liver transplants after hepatitis D virus (HDV)-related end-stage liver disease developed were examined, allowing a novel opportunity to study the evolution of HDV infection in relation to hepatitis B virus (HBV) infection from the earliest stages. Hepatitis D virus antigen was detected in liver tissue in the absence of either tissue or serologic evidence of HBV recurrence within 3 months in all eight patients biopsied at that time. After serologic evidence of recurrent HBV infection in nine patients, there was a massive increase in hepatic expression of hepatitis D virus antigen and this was associated with the transient appearance of serum hepatitis D virus antigen in four patients. Coexpression of both HBV and HDV antigens in the liver was associated with the onset of lobular hepatitis, which progressed to chronic hepatitis in five patients. These findings indicate that HDV can survive and synthesize HDAg in the absence of detectable HBV, but when HBV replication increased to a detectable level, HDV replication was enhanced massively. Contrary to current thinking, the data suggest that HDV is not directly cytopathic and that HBV is an essential cofactor in the evolution of hepatocellular damage. PMID- 1462953 TI - Pasteurella multocida endocarditis. AB - Human infection with Pasteurella multocida is the leading cause of animal bite wound infection. Life-threatening infection may occur in patients with a variety of underlying disorders and an immunocompromised state. Infective endocarditis with P. multocida is very rare and only a few clinically diagnosed cases have been reported. Described here is an autopsy case of a 61-year-old man with polycystic kidney disease who had P. multocida bacteremia and acute infective endocarditis with multiple bacterial clumps involving bicuspid aortic valve. The organisms were gram negative. Apparently the sepsis with P. multocida was acquired via licking of leg ulcers by his pet dog, establishing an animal-related causal relationship. Because P. multocida is a very common flora of many animals, infection with this organism probably occurs more frequently than is commonly appreciated. High index of suspicion and early diagnosis, especially in immunocompromised patients, are warranted because the disease is potentially life threatening, yet is a readily treatable infection. PMID- 1462954 TI - Helicobacter pylori-related gastritis and gastric ulcer. A continuum of progressive epithelial degeneration. AB - One hundred forty-five consecutive gastric biopsy specimens showing colonization by Helicobacter pylori (HP) were studied. Biopsy specimens were obtained from patients with the following conditions: gastric ulcer (GU; 76), active chronic gastritis (ACG; 52), GU with duodenal ulcer (DU; 10), and ACG with DU (7). The mean age of the patients in the ACG group was 8.6 years less than the patients in the GU group. Helicobacter pylori colonization and HP-induced epithelial degeneration (ED) were quantified by a grading system (grades 0 to 6) comprising both focal and global scores for bacterial density (HP grade) and severity of ED (ED grade). The ED grade was directly proportional to the HP grade in all biopsy specimens. Gastric ulcer biopsy specimens were associated with higher HP grades: HP grade more than 5 in 25 cases (32.9%) and ED grade more than 5 in 18 cases (23.6%) of GU compared with similar respective scores in 9 cases (17.9%) and 2 cases (3.8%) of ACG. The difference was due primarily to a higher global score of bacterial density and higher focal score of ED in the GU biopsy specimens. These results support the hypothesis that HP-positive ACG and HP-positive GU are lesions within a single disease spectrum. Heavy HP colonization and severe HP induced epithelial damage are predisposing factors in ulcerogenesis. Because HP positive ACG is probably a preulcerative state, eradication of the bacteria in HP positive ACG might prevent subsequent GU. PMID- 1462955 TI - The characteristics of mitotic figures in jejunal mucosa of patients with celiac disease. AB - The morphologic characteristics of the mitotic figures present in the jejunal mucosa of 23 pediatric patients having gluten enteropathy were recorded. Of the 851 mitoses found, 4.9% were in prophase, 39.9% in prometaphase, 29.5% in metaphase, 22.3% in anaphase, and 3.3% in telophase. Of the 851 mitoses found, 98.8% were considered to be morphologically normal and the remaining 1.2% were considered atypical. The occurrence of atypical mitoses in the jejunal mucosa of pediatric patients was unexpected. However, because jejunal adenocarcinomas in celiac patients are known to be rare, the plausible explanation for the present findings is that the occurrence of atypical mitoses may mirror morphologic variations from the normal mitotic pattern occurring in a rapidly proliferating mucosa, such as that of patients with gluten enteropathy. PMID- 1462956 TI - Renal oncocytoma and granular renal cell carcinoma. A comparative clinicopathologic and DNA flow cytometric study. AB - Twenty-three renal oncocytomas and 18 granular renal cell carcinomas (GRCC) were comparatively studied clinicopathologically and by DNA flow cytometry to delineate their differences. Of the patients with renal oncocytomas, 15 were men and 8 were women, and their ages ranged from 42 to 81 years (mean, 64 years). The gross appearance of renal oncocytomas was characteristically homogeneous tan brown, with variable scarring, without areas of large hemorrhage, and with no apparent necrosis. Twenty-two renal oncocytomas were confined within the kidney (Robson stage I) and one tumor extended into the renal vein (stage IIIa). Twenty two renal oncocytomas, including the stage IIIa tumor, manifested diploid DNA content and only one neoplasm showed a feature suggestive of near-diploid DNA aneuploidy. Of the 17 patients with renal oncocytomas who had adequate follow-up, none developed metastasis or died of disease. Of the patients with GRCC, 13 were men and 5 were women, and their ages ranged from 30 to 73 years (mean, 53 years). The gross appearance of GRCC was variegated, yellow to tan, and punctuated with geographic areas of necrosis. Eleven patients with GRCC were stage I, 4 were stage II, 2 were stage IIIa, and 1 patient had metastases at initial examination (stage IV). Seven GRCCs were DNA diploid, one was DNA tetraploid, and 10 tumors were DNA aneuploid. Twelve patients were alive with no evidence of disease (12 to 36 months; median, 26 months). All patients with DNA diploid neoplasm pursued benign clinical courses. One patient was alive with metastatic disease and two patients developed metastases and died of their disease; all three patients had DNA aneuploid tumors. Two patients died of other causes and one patient was lost to follow-up. Our data indicate that renal oncocytoma is a distinct clinicopathologic disease with characteristic gross, histologic, DNA flow cytometric, and biologic features that are different from GRCC. PMID- 1462957 TI - Osteolysis after silicone arthroplasty. AB - A young woman with a silicone lunate prosthesis for avascular necrosis developed painful lytic lesions in the distal ulna and the triquetrum. At reoperation, abundant reactive synovitis was found extending into those bone lesions. Histologic examination of the curetting samples revealed granulation tissue with histiocytes and many multinucleated giant cells containing refractile particles consistent with silicone. The authors report a giant cell lesion of the bone that radiographically and microscopically mimicked a neoplasm. PMID- 1462958 TI - Evaluation of the CELL-DYN 3000 differential. AB - The CELL-DYN 3000 (Unipath Corp., Mountain View, CA) differential was evaluated in a tertiary care hospital using samples with a broad range of distributional and morphologic abnormalities. Particular attention was directed to the performance of the instrument-generated suspect flags that occur as an aid to identify samples with abnormal leukocytes, as well as the estimates of abnormal cells that are made by the instrument. The CELL-DYN 3000 showed excellent quantitative results for the white blood cell differential compared with a 400 cell manual differential, in which morphologic abnormalities were absent or occurred in low numbers (< or = 5%). Specificity of the BLAST, VARIANT LYMPH, NRBC, WBC, or DIFF suspect flags (with the requirement that the blast estimate and variant lymphocyte estimate by the instrument be > or = 1%) was 82.6%. Sensitivity of these flags to detection of more than 5% "abnormal" leukocytes (blasts, malignant lymphoid cells, grossly dysplastic neutrophils, nucleated red blood cells, or reactive lymphocytes) or significant platelet clumping was 81.6%. The primary deficiency was the inability of the CELL-DYN 3000 to flag samples with small numbers (< or = 5%) of nucleated erythrocytes, lymphoid blasts, or hairy cells, or more than 5% reactive lymphocytes. Specificity of the IG flag (with immature granulocyte estimate > or = 3%) for immature granulocytes (metamyelocytes, myelocytes, or promyelocytes) was 94.9%. Sensitivity of the immature granulocyte flag varied from 41.7% for identifying IG > or = 1% to 100% for the three samples with immature granulocytes > or = 3%. Calculation of sensitivity and specificity to varying percentages of bands showed poor flagging performance, with many false-positive and false-negative results at all levels. PMID- 1462959 TI - A method for the independent assessment of the accuracy of hematology whole-blood calibrators. AB - An independent assessment of the accuracy with which a large manufacturer assigned values to hematologic calibrators was performed. Data were collected from 1,767 hospitals and clinics distributed over North America. Statistical analysis of the mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration of these patient data confirmed the accuracy of the values for hemoglobin, erythrocyte count, hematocrit, and erythrocyte indices for the calibrators manufactured and released during a 9-month period. This approach proved both workable and effective in detecting inaccuracies of less than 1%. Few technologist-users have the time or the equipment to verify independently the accuracy of hematologic calibrators. The manufacturers should perform ongoing, independent assessments of the accuracy of their products. The statistical analysis of patient data provides manufacturers with a suitable method. PMID- 1462960 TI - Multiple myeloma with tadpolelike cells and rosette formation. AB - A 65-year-old man with lower back pain was found to have multiple myeloma. Unique findings in the marrow aspirate smears of this patient were tadpolelike plasma cells and cellular rosettes simulating those seen in neuroblastoma. This case documents yet another facet of the broad morphologic spectrum of neoplastic plasma cells in multiple myeloma. PMID- 1462961 TI - Report of a case of localized Castleman's disease with progression to malignant lymphoma. AB - Patients with multicentric Castleman's disease have an increased risk of developing non-Hodgkin's lymphoma. However, development of lymphoma in the localized form of Castleman's disease has not been previously reported. This case study describes a patient with localized Castleman's disease, hyaline vascular type, whose course was complicated by follicular non-Hodgkin's lymphoma. PMID- 1462962 TI - Angiocentric versus angiotropic lymphoma. PMID- 1462963 TI - Autologous blood transfusion. PMID- 1462964 TI - Magnetic fields of video display terminals and spontaneous abortion. AB - The aim of this study was to examine whether work with a video display terminal and exposure to the magnetic fields of video display terminals are related to spontaneous abortion. The study was conducted among women employed as bank clerks and clerical workers in three companies in Finland. The cases (191 spontaneous abortions) and controls (394 births) were identified from Finnish medical registers for the years 1975-1985. Use of video display terminals was defined using the workers' own reports and information provided by the companies. The assessment of exposure to the magnetic fields was based on measurements of the fields of video display terminals. The odds ratio for spontaneous abortion for working with video display terminals was not increased (odds ratio = 1.1, 95% confidence interval 0.7-1.6). However, the odds ratio for workers who had used a video display terminal with a high level of extremely low frequency magnetic fields (> 0.9 microT) was 3.4 (95% confidence interval 1.4-8.6) compared with workers using a terminal with a low level of these magnetic fields (< 0.4 microT). Adjustment for ergonomic factors and mental work load factors changed the odds ratio for magnetic field exposure only very slightly. The findings suggest the need for future studies with assessment of exposure to the magnetic fields in the actual working environment to confirm the possible risk. PMID- 1462965 TI - Pregnancy and lactation as determinants of bone mineral density in postmenopausal women. AB - The relation of pregnancy and breast feeding to bone mineral density of the wrist, radius, hip, and spine was examined in a white, upper middle-class, homogeneous sample of 741 postmenopausal women ranging in age from 60 to 89 years. Number of pregnancies ranged from 0 to 14, with a mean of 2.0 pregnancies and 1.5 live births. Almost two thirds of the women who had had a live birth reported breast feeding. Unadjusted comparisons indicated that bone mineral density of the wrist, radius, and hip increased with increasing numbers of pregnancies, and women who had breast-fed had higher bone mineral densities at these sites. However, after adjustment for age or age and body mass index, these associations were no longer significant. Multiple regression analyses adjusted for age, age at menopause, obesity, cigarette smoking, and estrogen and thiazide use also indicated that number of pregnancies and breast feeding were not significantly associated with bone mineral density at any of the four sites measured. Results of the present study suggest that reproductive history and breast feeding are not long-term determinants of bone mineral density. PMID- 1462966 TI - Lipoprotein(a) concentrations in Mexican Americans and non-Hispanic whites: the San Antonio Heart Study. AB - There is considerable evidence that lipoprotein(a) (Lp(a)) is a strong independent risk factor for coronary heart disease. Based on their risk factor profile, Mexican Americans have an increased risk of coronary heart disease, yet Mexican Americans have coronary heart disease mortality similar to or lower than that of non-Hispanic whites. The authors therefore attempted to determine whether Mexican Americans had decreased Lp(a) concentrations relative to non-Hispanic whites in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Lp(a) concentrations (mg/dl) were significantly lower in Mexican Americans (n = 316) than in non-Hispanic whites (n = 242) (men: 10.4 vs. 16.3; women: 11.5 vs. 16.4). In addition, the proportion of persons with Lp(a) concentrations of > or = 30 mg/dl (the threshold at which increased risk of coronary heart disease is believed to occur) was significantly higher in non Hispanic whites than in Mexican Americans (18.6% vs. 7.6%; Mantel-Haenszel odds ratio (adjusted for sex) = 2.79). Age, obesity, body fat distribution, cigarette smoking, alcohol consumption, and glucose and insulin concentrations were not significantly related to Lp(a) levels. Decreased Lp(a) concentrations may account in part for Mexican Americans' relative protection from coronary heart disease mortality. PMID- 1462967 TI - Short-term intraindividual variability in lipoprotein measurements: the Atherosclerosis Risk in Communities (ARIC) Study. AB - Much epidemiologic research is based on estimation of an association between a putative risk factor and a health outcome--for example, plasma concentration of lipoproteins and ischemic heart disease. Since the repeatability of a risk factor measurement determines, in part, the ability to ascertain its association in populations, the Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability Study was conducted to estimate various components of variation in analyte data and to estimate the repeatability of these measurements. A total of 40 subjects (17 males and 23 females) from Forsyth County, North Carolina, Minneapolis, Minnesota, Jackson, Mississippi, and Washington County, Maryland, were studied in 1988. Fasting blood was collected three times from each subject, with a 1- to 2-week interval between each visit. The contributions of between person variability, within-person variability, and processing and assay variability were estimated. From these components, the reliability coefficient, R, the correlation between measures made at repeat visits, was estimated. R was above 0.85 for total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and lipoprotein(a). Low repeatability was obtained for apolipoprotein A-I (R = 0.60). High density lipoprotein subfractions 2 and 3 were intermediate in repeatability. Reliability coefficients from the ARIC Intraindividual Variability Study are generally higher than those found in other studies, and this is related to relative variability in populations studied, to the time between measurements, and to differences in laboratory variability. Only for apolipoprotein A-I would the findings strongly suggest the need to adjust for measurement variability in estimation using one of these analytes as an independent variable. PMID- 1462969 TI - Blood lead as a cardiovascular risk factor. AB - Many epidemiologic and experimental animal studies support the hypothesis of there being a causal association between lead exposure and increased blood pressure/cardiovascular disease. This study includes 1,052 men and women from Copenhagen County, Denmark, who were examined in 1976 and 1981; in 1987, only the men were examined. Blood lead fell by approximately 40% for the men during the 11 year period and by approximately 30% for the women during the first 5-year period. There was a univariate association between systolic blood pressure and blood lead for both sexes in 1976, but it disappeared at the following examinations. For women, there was also a significant association with diastolic blood pressure, even after confounders were controlled for at the two examinations. Moreover, the authors found a significant univariate association between changes in blood lead and changes in systolic blood pressure from 1976 to 1987 in the males. All participants taking part in the study in 1976 were followed regarding hospital admissions and deaths throughout a follow-up period lasting for 14 years. There was a significant univariate association with total mortality, coronary heart disease, and cardiovascular disease. However, with regard to coronary heart disease and cardiovascular disease, the associations disappeared when confounders were controlled for. Blood lead was a significant predictor of total mortality after control for relevant confounders. This study supports the hypothesis of there being a weak causal association between blood lead and blood pressure, total mortality, coronary heart disease, and cardiovascular disease. The importance of this association is very modest for the individual, but the population attributable risk may be considerable. PMID- 1462968 TI - Serum ceruloplasmin level and the risk of myocardial infarction and stroke. AB - The associations between serum ceruloplasmin level and the subsequent incidence of myocardial infarction and stroke were studied in a nested case-control study in Finland (baseline examination 1968-1972). Ceruloplasmin levels were measured in stored serum samples from 104 myocardial infarction or stroke cases occurring during a median follow-up of about 11 years and from 104 individually matched controls. High serum ceruloplasmin levels were significantly associated with higher future odds of myocardial infarction but not of stroke. The odds ratios for myocardial infarction and stroke comparing the highest and lowest tertiles of serum ceruloplasmin, adjusted for smoking, serum cholesterol, body mass index, hematocrit, hypertension, and diabetes, were 3.1 and 0.7, respectively. The results of the present study support the hypothesis that a high serum ceruloplasmin level is a risk factor for myocardial infarction. PMID- 1462970 TI - The roles of insulin, obesity, and fat distribution in the elevation of cardiovascular risk factors in impaired glucose tolerance. The San Luis Valley Diabetes Study. AB - The objective of this study was to determine whether a less favorable risk factor pattern for cardiovascular disease among persons with impaired glucose tolerance could be explained by fasting insulin, obesity, and/or a central distribution of body fat. Between 1984 and 1988, cardiovascular risk factors were examined cross sectionally in Hispanic and non-Hispanic white participants in the San Luis Valley Diabetes Study who had either impaired (n = 173) or normal (n = 1,107) glucose tolerance. Sex-specific analysis of covariance models were constructed to adjust risk factor levels for age, age and insulin, and age, insulin, body mass index, and centrality index. Both males and females with impaired glucose tolerance had higher age-adjusted mean diastolic blood pressures, heart rates, uric acid levels, and triglyceride levels and lower levels of high density lipoprotein (HDL) cholesterol and HDL3 cholesterol than normal subjects; differences were significant for all risk factors except HDL cholesterol and HDL3 cholesterol in males. Differences in diastolic blood pressure in males, and differences in heart rate and triglyceride in both sexes, remained significant after adjustment for all covariates. However, differences in uric acid in males and differences in diastolic blood pressure and HDL3 cholesterol in females were attenuated to borderline significance levels. Differences in uric acid and HDL cholesterol in females were diminished to nonsignificant levels, especially after adjustment for obesity-related measures. With few exceptions, fasting insulin did not appear to play a major role in accounting for differences in these risk factors. With adjustment, ethnic differences (Hispanic vs. non-Hispanic white) were smaller and were statistically significant less often than differences observed between impaired and normal glucose tolerant groups. The authors concluded that hyperinsulinemia, obesity, and a central body fat distribution accounted for some, but usually not all, of the less favorable cardiovascular risk factor pattern found in subjects with impaired glucose tolerance. PMID- 1462971 TI - Post-challenge glucose concentration, impaired glucose tolerance, diabetes, and cancer mortality in men. AB - The possibility that diabetes is associated with an elevated risk of cancer mortality has been discussed for many years. Recently, Levine et al. (Am J Epidemiol, 1990; 131:254-62) approached this issue by relating post-load plasma glucose concentration to cancer mortality. For men, there appeared to be a positive association between post-load glucose and mortality from cancer for all sites combined and for some specific sites. However, that analysis was based on only 298 cancer deaths among 11,521 men followed for 12 years. The current authors explored this issue in a cohort of 18,274 male civil servants, among whom there were 1,282 cancer deaths over 18-20 years of follow-up. There was no association between post-load glucose and cancer mortality, except for pancreatic cancer. A role for asymptomatic hyperglycemia in the etiology of cancer is not supported by the results of the present study. PMID- 1462972 TI - Sexual transmission of hepatitis C virus among female prostitutes and patients with sexually transmitted diseases in Fukuoka, Kyushu, Japan. AB - The authors investigated the prevalence of antibody to hepatitis C virus (anti HCV) in 404 female prostitutes, 428 clinic patients with a history of at least one episode of sexually transmitted disease, and 8,944 blood donors who served as the controls. All subjects were Japanese, and all studies were carried out in Fukuoka, Kyushu, Japan, in 1989. The prevalence of anti-HCV was significantly higher in the prostitutes (6.2%), in the female patients with sexually transmitted diseases (6.1%), and in the male patients with sexually transmitted diseases (2.9%) than in the controls (1.5%). Prevalence of anti-HCV increased with age in prostitutes and in the controls. The prevalence of anti-HCV in those who had been involved in prostitution for 1 year or more (8.1%) was higher than in those who had been involved in prostitution for less than 1 year (1.4%), but the difference was not statistically significant. One of the 152 anti-HCV negative prostitutes seroconverted between 1 and 2 years later. Among the subjects with sexually transmitted diseases, patients with a history of at least one episode of syphilis had a significantly higher prevalence of anti-HCV (4.4%) than the controls. Patients with acute urethritis and cervicitis also showed a high prevalence of anti-HCV (3.6% and 6.7%, respectively). These data support the possibility of sexual transmission of hepatitis C virus. PMID- 1462973 TI - Familial aggregation of a disease consequent upon correlation between relatives in a risk factor measured on a continuous scale. AB - Correlation between relatives in one or more risk factors for a disease will contribute to the risk in relatives of an affected individual, irrespective of the cause(s) of the correlation. In this paper, a model is proposed to quantify the relation between 1) the correlation (rho) between a random pair of relatives in a quantitative risk factor, 2) the dependence of the probability of being affected on a risk factor, assumed to be a logistic function and summarized by a risk ratio (RR) between upper and lower quartiles, and 3) the resultant disease association between relatives, represented as an odds ratio. For one risk factor, the odds ratio is almost independent of disease frequency across the range 0.001 0.1, and is approximately linearly related to rho on a logarithmic scale. An odds ratio between relatives of about 2 occurs if rho = 1 and RR = 9, if rho = 0.6 and RR = 20, or if rho = 0.3 and RR = 100. For two independent risk factors with the same risk ratio and rho, the resultant odds ratio exceeds unity by about twice as much as when there is one risk factor. That is, even moderate familial aggregation of a disease is consistent with there being one or more strong familial (genetic and/or environmental) risk factors. Illustrations of the model are discussed. PMID- 1462974 TI - Sample size for studying intermediate endpoints within intervention trails or observational studies. AB - An intermediate endpoint is a biologic event or marker that is a precursor to a given health outcome. Examples of potential intermediate endpoints include serum cholesterol for coronary heart disease, endogenous steroid hormones for breast cancer, and CD4 count for acquired immunodeficiency syndrome. When one is studying a potential intermediate endpoint in the context of an intervention trial, five types of questions may be investigated: 1) Does the intervention affect the intermediate endpoint? 2) Is the intermediate endpoint associated with prognostic or risk factors? 3) Is the intermediate endpoint associated with the main outcome? 4) Is the intervention effect on the main outcome mediated by the intermediate endpoint? 5) Are the prognostic or risk factor effects mediated by the intermediate endpoint? In this paper, the authors show that each of these questions had different sample size requirements, and they illustrate their point with a discussion of an ancillary study of large bowel epithelial proliferation in the National Cancer Institute's Polyp Prevention Trial. The same methods may be used in an observational study, in which case questions 2, 3, and 5 are relevant. However, much larger numbers than those used in the Polyp Prevention Trial example will be required when the main outcome is rare. PMID- 1462975 TI - Leave no stone unturned. AB - The need for locating patients lost to follow-up is well known in epidemiologic research projects. This paper provides for the reader the basic tools, techniques, and methods that can be used to locate these patients. PMID- 1462976 TI - Re: "Dietary cholesterol and incidence of lung cancer: the Western Electric Study". PMID- 1462977 TI - Re: "Dietary antioxidants and the risk of lung cancer" and "Dietary cholesterol and incidence of lung cancer: the Western Electric Study". PMID- 1462978 TI - Re: "A simple method to calculate the confidence interval of a standardized mortality ratio (SMR)". PMID- 1462979 TI - Re: "Tests for trend and dose response: misinterpretations and alternatives". PMID- 1462980 TI - Diabetic nephropathy in insulin-dependent patients. AB - Diabetic nephropathy is a serious complication of insulin-dependent diabetes mellitus (IDDM) that affects 30% to 40% of IDDM patients with a predictable time of onset. Epidemiologic data suggest that either a genetic susceptibility, perhaps for hypertension (HTN), or an environmental exposure selects out that subset of IDDM patients and destines them to develop diabetic nephropathy. Hopefully, assessing glomerular hyperfiltration, urinary albumin excretion rate (AER), glycemic control, mean arterial pressure (MAP), and perhaps early morphologic changes will allow early identification of this high-risk group of IDDM patients before overt nephropathy is present. Once nephropathy appears, renal function inexorably declines, although the natural history of this progression may be changing with earlier therapeutic intervention. IDDM patients with nephropathy suffer a high mortality rate compared with IDDM patients without nephropathy or with nondiabetic end-stage renal disease patients. This is primarily due to malignant atherosclerotic disease manifested as coronary, peripheral, and cerebral arterial disease. Therapeutic interventions of demonstrated benefit in slowing the rate of decline of glomerular filtration rate (GFR) include blood pressure control and low-protein diets. Strict blood sugar control or treatment with aldose reductase inhibitors, converting enzyme inhibitors (CEIs), or inhibitors of advanced glycosylation end-product formation are of possible benefit, but are awaiting clinical trial results. PMID- 1462981 TI - An overview of renal pathology in insulin-dependent diabetes mellitus in relationship to altered glomerular hemodynamics. AB - Clinical diabetic nephropathy in man is the consequence of the development of a specific constellation of glomerular, tubular, vascular, and interstitial structural abnormalities accompanied by highly characteristic immunohistochemical alterations that, together, are unique to diabetes. Because changes resembling the specific pathology of diabetes do not develop in patients with conditions that lead to long-standing glomerular hyperfunction (such as unilateral nephrectomy), it is unlikely that glomerular hemodynamic abnormalities per se can be the cause of diabetic nephropathy. Whether hemodynamic abnormalities represent a risk factor that, in the presence of the diabetic state, can accelerate the rate of development of the basic lesions of diabetic nephropathy is currently unclear. However, there is considerable evidence that when the renal lesions of diabetes are far advanced, factors such as systemic hypertension can determine the rate of renal functional deterioration in diabetes as in other disorders. Although the diabetic rat may be a useful model for the study of aspects of the pathogenesis of diabetic nephropathy, much confusion has resulted from the inclusion of focal segmental glomerular sclerosis as a diabetic lesion. Similarly, the acceptance of all increases in urinary protein excretions in this model as resulting from or reflecting of diabetic nephropathology can be misleading. It is concluded that treatment aimed at manipulating renal hemodynamics in diabetic patients without evidence of renal disease should remain in the realm of clinical research. PMID- 1462982 TI - Captopril acutely lowers albuminuria in normotensive patients with diabetic nephropathy. AB - Angiotensin-converting enzyme (ACE) inhibitors decrease albuminuria in patients with diabetic nephropathy. To study the change in albuminuria in relation to changes in systemic and renal hemodynamics, nine normotensive patients with type 1 (insulin-dependent) diabetes mellitus and persistent proteinuria were given a single oral dose of 25 mg of the ACE inhibitor captopril. Blood pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and albumin excretion rate (AER) were measured in two periods of 40 minutes before and in four periods of 40 minutes after administration of captopril. A constant water diuresis was maintained. Blood pressure did not decrease significantly (130/79 +/ 4/3 v 124/74 +/- 4/3 mm Hg; mean +/- SEM), median AER decreased from 403 (interquartile range [IQR], 812) micrograms/min to 333 (707) micrograms/min (P < 0.01). GFR did not change (123 +/- 13 v 117 +/- 14 mL/min), but ERPF increased significantly from 609 +/- 56 to 714 +/- 55 mL/min (P < 0.01). Consequently, the filtration fraction (FF; quotient of GFR and ERPF) decreased from 0.20 +/- 0.014 to 0.17 +/- 0.014 (P < 0.01). A strong correlation was found between the decrease of AER and the decrease of FF (rs = 0.75; P < 0.02). No correlation was found between the decrease in AER and changes in GFR or blood pressure. In the normotensive patient with diabetic nephropathy, captopril causes an acute reduction of AER, which is probably mediated by a lowering of the intraglomerular pressure. PMID- 1462983 TI - Renal replacement therapy in type 2 diabetic patients: 10 years' experience. AB - The objective of this study was to determine the impact of renal transplantation and hemodialysis treatment on outcome of elderly diabetic patients with end-stage renal disease (ESRD) among other factors related to survival. Results of treatment of ESRD in 78 patients with non-insulin-dependent diabetes mellitus (type 2) showed a survival rate of 58% at 1 year and 14% at 5 years, independent of treatment modality. Patients who received a renal allograft had a higher survival rate as compared with patients on hemodialysis treatment (5-year survival, 59% v 2%; P < 0.005). Diabetic patients with a history of myocardial infarction, stroke, or peripheral gangrene before onset of renal replacement therapy had a worse prognosis in comparison to patients without vascular complications (5-year survival, 2% v 21%; P < 0.05). Analysis of patients who survived less than 6 months and more than 24 months was performed. Long-term survivors were slightly younger, had diabetes for a shorter period, and showed a better metabolic control of diabetes mellitus. Sixteen long-term survivors received a renal allograft. In contrast, only three short-term survivors were transplanted. Furthermore, short-term survivors also had a greater than 70% incidence of severe vascular complications before renal replacement therapy. A history of myocardial infarction, stroke, or peripheral gangrene is an independent predictor of decreased survival, irrespective of whether the patients were transplanted or maintained on chronic hemodialysis treatment. In contrast, renal transplantation improved survival of elderly diabetic patients without vascular complications and should be the treatment of choice in this specific group of patients. PMID- 1462984 TI - Renal scanning 99mTc diethylene-triamine pentaacetic acid glomerular filtration rate (GFR) determination compared with iothalamate clearance GFR in diabetics. The Collaborative Study Group for The study of Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy. AB - Traditionally, creatinine clearance is used as an estimation of the glomerular filtration rate (GFR) because of its relative ease and low cost. Errors in collection limit its usefulness. Estimation of GFR using 99mTc diethylene triamine pentaacetic acid (Tc-DTPA) by direct scintigraphic determination of fractional radionuclide accumulation within each kidney does not require blood or urine sampling, takes 10 to 15 minutes to perform, and has been reported to give a GFR that correlates with 24-hour urinary creatinine clearance (CC) in hospitalized patients (r = 0.95). To assess its usefulness in the outpatient diabetic with nephropathy, 24 patients with type I diabetes underwent 56 iothalamate clearances during water diuresis and 56 simultaneous Tc-DTPA GFR estimations. GFR was also estimated from 24-hour urinary CC, 100/creatinine, and by the formula of Cockcroft and Gault. Tc-DTPA GFR estimation by direct renal scanning correlated relatively poorly with iothalamate GFR (r = 0.74) in this patient population when all levels of iothalamate GFR were compared (n = 56), but improved (r = 0.80) when iothalamate GFR values greater than or equal to 120 mL/min were excluded from analysis (n = 45). Given all levels of iothalamate GFR, the best correlation was obtained with the estimation using the equation of Cockcroft and Gault (r = 0.86). PMID- 1462985 TI - The diagnosis of Helicobacter pylori infection in uremic patients. AB - Two urease-based tests--the urease slide test and the radiolabeled urea breath test, are commonly used for the diagnosis of Helicobacter pylori infection of the stomach. The reliability of these tests in chronic uremia was compared with serological tests for H pylori antibodies, and with direct detection of the organism by microscopy or culture of gastric antral biopsies. Twenty-seven patients with chronic renal failure and dyspepsia underwent upper gastrointestinal endoscopy. Twelve of these patients (46%) were judged to be infected with H pylori on the basis of identification of the organism on microscopy or culture of antral biopsy. Both urease-based tests were able to determine H pylori status, despite the markedly increased concentrations of urea in the gastric juice found in chronic renal failure. The urease slide test performed on antral biopsies obtained at endoscopy proved reliable in determining H pylori status with no false-positive nor false-negative results after 20 minutes and 24 hours of incubation. The 14C-urea breath test also differentiated the infected from the uninfected patients. The 20-minute 14CO2 excretion (kg %dose/mmol CO2 x 100) ranged from 50 to 834 in the H pylori-infected patients, compared with 0.3 to 27 in the H pylori-noninfected patients (P < 0.0001); the 90 minute values ranged from 88 to 398 in the former, compared with 1 to 79 in the latter (P < 0.0001). The excretion of 14CO2 (derived from bacterial hydrolysis of ingested 14C-urea) was higher in all the uremic patients compared with nonuremic controls, and in half of the H pylori-noninfected uremic patients there was a late increase in 14CO2 excretion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1462986 TI - Iron accumulation in human chronic renal disease. AB - Iron, which has been shown to accumulate within proximal tubule lysosomes in proteinuric models of renal disease, may play a role in the progression of chronic renal disease by the generation of reactive oxygen species. Therefore, renal biopsies from humans with proteinuria and/or chronic renal failure were examined at an ultrastructural level for iron by energy dispersive analysis and compared with normal biopsies. Iron accumulated in proximal tubular lysosomes in renal disease (P < 0.05 v normals), accompanied in some cases by phosphorus and silicon. Both the number of iron-containing lysosomes per tubular cross-section (1.86 +/- 0.41 v 0.66 +/- 0.22, P < 0.05) and the mean concentration of lysosomal iron (254.5 +/- 73.4 mg/dL v 81.2 +/- 23.8, P < 0.001) was greater in patients with nephrotic syndrome (n = 12) than in those without (n = 8). Iron accumulation (number of iron-containing lysosomes/tubule) correlated with protein excretion (r = 0.68, P = 0.003, n = 20), but not with glomerular filtration rate. Damaged tubules contained greater amounts of iron than tubules with less damage (288.5 +/ 68.5 mg/dL v 80.4 +/- 13.9, P < 0.01). Further studies are needed to define the possible role of iron in causing tubular damage and progression of renal disease. PMID- 1462987 TI - Uremic pancreopathy: impaired secretory function in vitro. AB - Abnormalities of the exocrine pancreas have long been described in uremia. The present study was performed to determine whether these abnormalities occur as a result of derangements in protein synthesis or disturbances in protein secretion. Pancreatic acini obtained from rats with renal failure and their pair-fed shams were studied in vitro by the method of radiolabeled leucine incorporation and secretory response to carbachol. In vitro protein synthesis, as reflected in radiolabeled leucine incorporation per DNA content was increased in uremic acini compared with control. However, the secretory response to carbachol was impaired. These results suggest that the impairment in exocrine pancreatic function is likely due to abnormalities in protein secretion, rather than protein synthesis. PMID- 1462989 TI - The determination of hemodialysis blood recirculation using blood urea nitrogen measurements. AB - The determination of blood recirculation using blood urea nitrogen (BUN) measurements in hemodialysis patients is a standard technique. The accuracy and reproducibility of these calculations have never been determined. Two pairs of recirculation studies (study A and study B) were performed in 13 patients during a single dialysis treatment. Blood samples were analyzed for BUN and recirculation was calculated. The first recirculation study (study A) was performed within 1 hour of the initiation of dialysis, with a duplicate test of recirculation performed within 15 minutes. In study B, the dialyzer blood lines were reversed in an attempt to enhance blood recirculation. After 15 minutes, duplicate tests of recirculation were again performed. Calculated recirculations before the line reversal (study A) ranged from -3.3% to 11.9% in the first test and -2.9% to 12.2% in the second test. In study A, there was no correlation (P > 0.05, r = 0.09) between the first and second calculated recirculations. In study B, an increase in recirculation was observed. Calculated recirculations ranged from 16.3% to 53.5% for the first test and 5.4% to 58.1% for the second test. A significant relationship was observed in the calculated recirculation in study B (P < 0.05, r = 0.81). The results from the present study show that the use of BUN measurements may not provide a consistent indicator of access recirculation in a patient with a low recirculation. This lack of consistency should be considered when determining further clinical treatment. PMID- 1462988 TI - Eating behavior in continuous ambulatory peritoneal dialysis and hemodialysis patients. AB - Three groups consisting of 12 subjects each (continuous ambulatory peritoneal dialysis [CAPD] patients, hemodialysis patients, and healthy controls) matched for age, sex, and body weight were invited to a test meal for the study of hunger, fullness, and food preferences. They were served an excess portion of hash served on a plate placed on a hidden scale ("VIKTOR"), which was connected to a computer registering the eating process on-line. The patients filled in visual analogue scales (VAS) concerning appetite and food preferences before and after the test meal. Mean total intake of food (+/- SD) was significantly higher for healthy controls (357 +/- 175 g) compared with hemodialysis patients (295 +/- 105 g), which in turn was higher than in CAPD patients (206 +/- 70 g). Eating velocity was lower in both dialysis groups compared with controls. CAPD patients experienced less hunger and desire to eat compared with hemodialysis patients and controls. The reason for the low eating drive in CAPD patients despite their great need for protein and calories is unknown, but might be explained by gastric retention, insufficient dialysis, metabolic effects of the high sugar load from the dialysate, or combinations of these factors. PMID- 1462990 TI - Antilymphocyte globulin versus OKT3 induction therapy in cadaveric kidney transplantation: a prospective randomized study. AB - Different induction therapies have been used in renal transplantation to avoid cyclosporine (CsA) nephrotoxicity and early acute graft rejection. This study compares the efficacy of a short course of prophylactic OKT3 to that of antilymphocyte globulin (ALG) in preventing acute renal allograft rejection when administered concomitantly with CsA and steroids. Between March 1988 and December 1990, 140 first-cadaver renal transplant recipients were randomly allocated to two immunosuppression groups--ALG group (n = 68): ALG 15 mg/kg just before transplant surgery, ALG 12 mg/kg the first day after transplant, followed by four doses of 10 mg/kg on alternate days; and OKT3 group (n = 72): OKT3 5 mg just before transplant, followed by four doses of 5 mg/d. Both groups included low dose CsA and steroids. The incidence of rejection during the first 3 months after transplantation was 15% in the ALG group and 19% in the OKT3 group (NS). Kaplan Meier estimates of patients free of rejection at 2 years was 85% in the ALG group and 77% in the OKT3 group (NS). The 3-year actuarial graft survival was 82% and 85% (NS), and 3-year patient survival was 97% and 98% (NS), in the ALG and OKT3 groups, respectively. These results indicate that the concomitant association of CsA and ALG or OKT3 constitutes a safe and effective therapeutic strategy that provides a low incidence of rejection and gives good results for patient and graft survival. PMID- 1462991 TI - Cytokine-induced immunoglobulin production in primary IgA nephropathy. AB - Increased IgA synthesis probably plays a role in the pathogenesis of IgA nephropathy (IgAN). We investigated whether an increased sensitivity to the effect of various growth factor combinations leads to increased immunoglobulin synthesis by peripheral blood mononuclear cells (PBMC) from IgAN patients, in comparison to healthy controls. Although none of the growth factors studied (pokeweed mitogen [PWM], interleukin [IL]-2, IL-6, transforming growth factor beta [TGF-beta], and combinations) led to greater IgA synthesis in IgAN patients than in controls, the IgA subclass ratio was shifted in favor of IgA1. In controls, but not in IgAN patients, IL-2 enhanced the production of IgA and IgA1 compared with media alone. This possibly reflects previous in vivo activation by IL-2 in IgAN patients. The suppressive effect of TGF-beta on immunoglobulin synthesis was modestly greater in IgAN patients than in controls. Increased production of IL-2 and perhaps other cytokines by T cells in vivo may be responsible for the elevated IgA immune response in these patients. PMID- 1462992 TI - Analysis of cytodiagnostic urinalysis findings in 77 patients with concurrent renal biopsies. AB - We investigated the value of cytodiagnostic urinalysis in detecting and scoring the severity of the four types of renal lesions (glomerular, interstitial, tubular, and vascular). Both cytodiagnostic urinalysis and concurrent renal biopsy were performed in 77 patients (47 from native kidneys and 30 from transplants) and the scoring and findings assessed in a double-blinded fashion. Evaluation of the reproducibility for the counting of renal cells showed a low intraobserver and interobserver variation. Cytodiagnostic urinalysis correlated with the renal biopsy with respect to primary lesions in 42 (89%) of the native kidney cases, and in 23 (77%) of the transplant kidney cases. The accuracy of diagnosis of glomerular lesions in both native and transplanted kidneys was 0.91, and for acute rejection in transplanted kidneys, the accuracy of diagnosis was 0.73. Severity scores showed good correlation between cytodiagnostic urinalysis and renal biopsy in both transplanted and in native kidneys and cytodiagnostic urinalysis correlated well with the increase in creatinine levels. The most important components of cytodiagnostic urinalysis for the diagnosis of glomerular lesions were dysmorphic erythrocytes and proteinuria. The specificity and sensitivity of dysmorphic erythrocytes for a glomerular lesion were 0.89 and 0.88, respectively. In cases with biopsy-proven glomerular lesions, more severe changes were found by cytodiagnostic urinalysis when the biopsy showed proliferative lesions in the glomeruli than when normal glomeruli were found by light microscopy. Cytodiagnostic urinalysis has the advantage over renal biopsy that it can be repeated as often as necessary and thus allows observation of the development or regression of the renal lesion over time. We conclude that cytodiagnostic urinalysis is well correlated with the renal biopsy and that it provides valuable and quantitative information regarding the disease process in the kidney. PMID- 1462993 TI - Obesity-associated focal segmental glomerulosclerosis: pathological features of the lesion and relationship with cardiomegaly and hyperlipidemia. AB - In a review of the autopsies and medical records of 22 obese patients, focal segmental glomerulosclerosis (FSGS) was present in seven. The FSGS was mild in all but one patient. The FSGS of obese patients has similar features to idiopathic FSGS; however, our findings suggest that it lacks the hyperplasia of glomerular epithelial cells, shows no predilection for the corticomedullary junction, and is probably more often seen in the hilar region of the glomeruli. FSGS or glomerulomegaly was not associated with the degree of obesity. We demonstrated lipid deposition in the kidney of obese patients. Obese patients with FSGS, compared to those without FSGS, had higher blood cholesterol (P < 0.10) and higher triglyceride levels (P < 0.01). The mean heart weight of obese patients with FSGS was greater than that of patients without FSGS (P < 0.01). Also, obese patients with FSGS had larger glomeruli (246 +/- 33 microns) than obese patients without FSGS (218 +/- 16 microns) (P < 0.05). These findings suggest that cardiomegaly with hemodynamic changes and glomerular hyperfiltration may play a significant role in the glomerulomegaly and FSGS of obese patients. The secondary or contributory role of lipids in the development of the FSGS of obese patients remains to be determined. PMID- 1462994 TI - Acute myoglobinuric renal failure in a patient with IgA nephropathy. PMID- 1462995 TI - Sclerosing peritonitis with gross peritoneal calcification: a case report. AB - We report the case of a patient on dialysis for 13 years, including continuous ambulatory peritoneal dialysis (CAPD) for 11 years, who developed sclerosing peritonitis with gross peritoneal calcification. The patient first presented with abdominal pain in January 1990, when peritoneal calcification was detected for the first time. Her symptoms settled spontaneously and 1 year later she presented with acute peritonitis and adynamic ileus. The peritonitis settled with antibiotics and Tenchkoff catheter removal, but the ileus persisted. She was commenced on long-term parenteral nutrition, but never recovered useful bowel function. After 8 weeks of hemodialysis and total parenteral nutrition, a further laparotomy for an acute abdomen showed what appeared to be extensive bowel infarction and peritoneal calcification. She died several days later. Of significance, peritoneal calcification was first noted on x-ray and computed tomography (CT) scan while the patient was still largely asymptomatic and before peritoneal ultrafiltration capacity was significantly impaired. Unlike other reported cases of calcifying peritonitis, sclerosing peritonitis was present and calcification was far more extensive. It was not associated with factors such as frequent infective peritonitis or acetate dialysate. Calciphylaxis was not present nor was there any abnormality of calcium-phosphate metabolism. The outcome of this case suggests that patients with recurrent or persistent bowel symptoms on long-term CAPD should have early abdominal x-ray or CT scanning to exclude sclerosing peritonitis or bowel calcification. If present, consideration should be given to transferring the patient to another therapeutic dialysis modality if possible. PMID- 1462996 TI - Acute skin and fat necrosis during sepsis in a patient with chronic renal failure and subcutaneous arterial calcification. AB - Calcification of small subcutaneous arteries and arterioles is commonly found in patients with chronic renal failure (CRF), but the syndrome of acute ischemic necrosis of the skin and subcutaneous fat supplied by these vessels is relatively uncommon. The necrosis occurs during dialysis and after successful renal transplantation, and it is often fatal. Occlusion of the calcified arteries and associated microvessels by thrombi is reported infrequently, but it is relevant to the necrosis. However, the pathogenesis remains enigmatic. In the patient described here, who had CRF, bacteremia, and laboratory evidence of disseminated intravascular coagulation (DIC), the distribution of thrombi and necrosis was mainly that of the calcified arteries which, therefore, probably played a role in the localization of the thrombi. An increased susceptibility of the endothelium of calcified vessels to the procoagulant effects of sepsis may be a contributing factor. PMID- 1462997 TI - Neurotoxicity of acyclovir in patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis. AB - We report two cases of herpes-zoster in which the administration of acyclovir to patients with end-stage renal failure treated by continuous ambulatory peritoneal dialysis (CAPD) resulted in acyclovir neurotoxicity, even though the doses administered were within those recommended by the manufacturer's data sheet for patients with renal failure. Acyclovir removal was negligible with peritoneal dialysis and one patient died. The other patient was successfully treated with hemodialysis, which effectively reduced plasma concentrations, resulting in an improvement in conscious state. Acyclovir neurotoxicity should be considered in patients with renal failure who have been treated for viral infections, in whom the conscious state has deteriorated despite normal brain computed tomography (CT) scan and lumbar puncture investigations. Hemodialysis is the preferred treatment for the rapid removal of acyclovir. PMID- 1462998 TI - Acetazolamide in hemodialysis patients: a rational use after ocular surgery. AB - Acetazolamide is a weak diuretic used to decrease production of aqueous humor in the eye. Hemodialysis patients undergoing ocular surgery may benefit from acetazolamide; however, no pharmacokinetic data are available for this group of patients. We report a patient who received acetazolamide 250 mg every 6 hours after ophthalmic surgery and developed reversible neurological side effects associated with very high plasma concentrations. Using pharmacokinetic analysis, we suggest an alternate administration of acetazolamide for end-stage renal patients. PMID- 1462999 TI - Appropriate Blood Pressure Control in type II diabetes (ABCD Trial): implications for complications. PMID- 1463000 TI - Proteinuria, hematuria, hypertension, and decreased renal function in a patient with diabetes for 9 years. PMID- 1463001 TI - Children are different: the challenges of pediatric renal transplantation. PMID- 1463002 TI - Kidney disease and hypertension in blacks. PMID- 1463003 TI - Modification of diet in renal disease. PMID- 1463004 TI - Multicystic renal dysplasia in two consecutive male infants. PMID- 1463005 TI - Mitochondrial genetics: principles and practice. PMID- 1463006 TI - Segregation and manifestations of the mtDNA tRNA(Lys) A-->G(8344) mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome. AB - We have studied the segregation and manifestations of the tRNA(Lys) A-->G(8344) mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA(Lys) mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, and mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrome had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that > 92% of mtDNA with the tRNA(Lys) mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA(Lys) mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. In two of the patients with MERRF syndrome, muscle specimens were obtained at different times. In both cases, biochemical measurements revealed a deteriorating respiratory-chain function, and in one case a progressive increase in the amount of cytochrome c oxidase-deficient muscle fibers was found. PMID- 1463007 TI - A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology. AB - The Tas2 and Vic2 Australian families are affected with a variant of Leber hereditary optic neuropathy (LHON). The risk of developing the optic neuropathy shows strict maternal inheritance, and the ophthalmological changes in affected family members are characteristic of LHON. However, in contrast to the common form of the disease, members of these two families show a high frequency of vision recovery. To ascertain the mitochondrial genetic etiology of the LHON in these families, both (a) the the nucleotide sequences of the seven mitochondrial genes encoding subunits of respiratory-chain complex I and (b) the mitochondrial cytochrome b gene were determined for representatives of both families. Neither family carries any of the previously identified primary mitochondrial LHON mutations: ND4/11778, ND1/3460, or ND1/4160. Instead, both LHON families carry multiple nucleotide changes in the mitochondrial complex I genes, which produce conservative amino acid changes. From the available sequence data, it is inferred that the Vic2 and Tas2 LHON families are phylogenetically related to each other and to a cluster of LHON families in which mutations in the mitochondrial cytochrome b gene have been hypothesized to play a primary etiological role. However, sequencing analysis establishes that the Vic2 and Tas2 LHON families do not carry these cytochrome b mutations. There are two hypotheses to account for the unusual mitochondrial genetic etiology of the LHON in the Tas2 and Vic2 LHON families. One possibility is that there is a primary LHON mutation within the mitochondrial genome but that it is at a site that was not included in the sequencing analyses. Alternatively, the disease in these families may result from the cumulative effects of multiple secondary LHON mutations that have less severe phenotypic consequences. PMID- 1463008 TI - No significant effect of monosomy for distal 21q22.3 on the Down syndrome phenotype in "mirror" duplications of chromosome 21. AB - Three Down syndrome patients for whom karyotypic analysis showed a "mirror" (reverse tandem) duplication of chromosome 21 were studied by phenotypic, cytogenetic, and molecular methods. On high-resolution R-banding analysis performed in two cases, the size of the fusion 21q22.3 band was apparently less than twice the size of the normal 21q22.3, suggesting a partial deletion of distal 21q. The evaluation of eight chromosome 21 single-copy sequences of the 21q22 region--namely, SOD1, D21S15, D21S42, CRYA1, PFKL, CD18, COL6A1, and S100B- by a slot blot method showed in all three cases a partial deletion of 21q22.3 and partial monosomy. The translocation breakpoints were different in each patient, and in two cases the rearranged chromosome was found to be asymmetrical. The molecular definition of the monosomy 21 in each patient was, respectively, COL6A1 S100B, CD18-S100B, and PFKL-S100B. DNA polymorphism analysis indicated in all cases a homozygosity of the duplicated material. The duplicated region was maternal in two patients and paternal in one patient. These data suggest that the reverse tandem chromosomes did not result from a telomeric fusion between chromosomes 21 but from a translocation between sister chromatids. The phenotypes of these patients did not differ significantly from that of individuals with full trisomy 21, except in one case with large ears with an unfolded helix. The fact that monosomy of distal 21q22.3 in these patients resulted in a phenotype very similar to Down syndrome suggests that the duplication of the genes located in this part of chromosome 21 is not necessary for the pathogenesis of the Down syndrome features observed in these patients, including most of the facial and hand features, muscular hypotonia, cardiopathy of the Fallot tetralogy type, and part of the mental retardation. PMID- 1463009 TI - Analysis of chromosome 21 yeast artificial chromosome (YAC) clones. AB - Chromosome 21 contains genes relevant to several important diseases. Yeast artificial chromosome (YAC) clones, because they span > 100 kbp, will provide attractive material for initiating searches for such genes. Twenty-two YAC clones, each of which maps to a region of potential relevance either to aspects of the Down syndrome phenotype or to one of the other chromosome 21-associated genetic diseases, have been analyzed in detail. Clones total approximately 6,000 kb and derive from all parts of the long arm. Rare restriction-site maps have been constructed for each clone and have been used to determine regional variations in clonability, methylation frequency, CpG island density, and CpG island frequency versus gene density. This information will be useful for the isolation and mapping of new genes to chromosome 21 and for walking in YAC libraries. PMID- 1463010 TI - Nondisjunction of chromosome 21: comparisons of cytogenetic and molecular studies of the meiotic stage and parent of origin. AB - In the present report, we summarize studies aimed at examining the reliability of chromosome heteromorphisms in analyses of chromosome 21 nondisjunction. We used two cytogenetic approaches--fluorescent in situ hybridization (FISH) to repetitive sequences on 21p and traditional Q-banding--to distinguish chromosome 21 homologues and then compared the results of these studies with those obtained by DNA markers. Using a conservative scoring system for Q-banding and FISH heteromorphisms, we were able to specify the parental origin of trisomy in 10% of cases; in contrast, DNA marker studies were informative for parental origin in almost all cases. The results of the molecular and cytogenetic studies of parental origin concurred in all cases in which assignments were made independently using both techniques. However, in 4 of 13 cases in which the molecular studies contributed to the interpretation of the cytogenetic findings, the two results did not agree with respect to the meiotic stage of nondisjunction. A relatively high frequency of crossing-over on either the short arm or proximal long arm of chromosome 21 could explain these results and may be a mechanism leading to nondisjunction. PMID- 1463011 TI - Xp21 contiguous gene syndromes: deletion quantitation with bivariate flow karyotyping allows mapping of patient breakpoints. AB - Bivariate flow karyotyping was used to estimate the deletion sizes for a series of patients with Xp21 contiguous gene syndromes. The deletion estimates were used to develop an approximate scale for the genomic map in Xp21. The bivariate flow karyotype results were compared with clinical and molecular genetic information on the extent of the patients' deletions, and these various types of data were consistent. The resulting map spans > 15 Mb, from the telomeric interval between DXS41 (99-6) and DXS68 (L1-4) to a position centromeric to the ornithine transcarbamylase locus. The deletion sizing was considered to be accurate to +/- 1 Mb. The map provides information on the relative localization of genes and markers within this region. For example, the map suggests that the adrenal hypoplasia congenita and glycerol kinase genes are physically close to each other, are within 1-2 Mb of the telomeric end of the Duchenne muscular dystrophy (DMD) gene, and are nearer to the DMD locus than to the more distal marker DXS28 (C7). Information of this type is useful in developing genomic strategies for positional cloning in Xp21. These investigations demonstrate that the DNA from patients with Xp21 contiguous gene syndromes can be valuable reagents, not only for ordering loci and markers but also for providing an approximate scale to the map of the Xp21 region surrounding DMD. PMID- 1463012 TI - Both inherited susceptibility and environmental exposure determine the low density lipoprotein-subfraction pattern distribution in healthy Dutch families. AB - A lipoprotein profile characterized by a predominance of small, dense, low density lipoprotein (LDL) particles has been associated with an increased risk of atherosclerosis. To investigate whether genetic factors are involved in determining this heavy LDL subfraction pattern, this study was undertaken with the aim of resolving the effects that major genes, multifactorial heritability, and environmental exposures have on the LDL subfraction pattern. In a random sample of 19 healthy Dutch families including 162 individuals, the distribution of the LDL subfraction pattern was determined by density gradient ultracentrifugation. For each subject a specific LDL subfraction profile was observed, characterized by the relative contribution of the three major LDL subfractions--LDL1 (d = 1.030-1.033 g/ml), LDL2 (d = 1.033-1.040 g/ml), and LDL3 (d = 1.040-1.045 g/ml)--to total LDL. A continuous variable, parameter K, was defined to characterize each individual LDL subfraction pattern. Complex segregation analysis of this quantitative trait, under a model which includes a major locus, polygenes, and both common and random environment, was applied to analyze the distribution of the LDL subfraction pattern in these families. The results indicate that the LDL subfraction pattern, described by parameter K, is controlled by a major autosomal, highly penetrant, recessive allele with a population frequency of .19 and an additional multifactorial inheritance component. The penetrance of the more dense LDL subfraction patterns, characterized by values of K < 0, was dependent on age, gender, and, in women, on oral contraceptive use and postmenopausal status. Furthermore, multiple regression analysis revealed that approximately 60% of the variation in the LDL subfraction pattern could be accounted for by alterations in age, gender, relative body weight, smoking habits, hormonal status in women, and lipid and lipoprotein levels. In conclusion, our results indicate that genetic influences as well as environmental exposure, sex, age and hormonal status in women are important in determining the distribution of the LDL subfraction patterns in this population and that these influences may contribute to the explanation of familial clustering of coronary heart disease. PMID- 1463013 TI - The gender-specific apolipoprotein E genotype influence on the distribution of plasma lipids and apolipoproteins in the population of Rochester, Minnesota. II. Regression relationships with concomitants. AB - The influence of the apolipoprotein E (Apo E) polymorphism and gender on the regression relationships between each of nine plasma lipid and apolipoprotein traits (total cholesterol; ln triglycerides; high-density-lipoprotein cholesterol; apolipoproteins AI, AII, B, and CII; ln CIII; and ln E) and four concomitants (age, weight, waist-to-hip ratio, and smoking) was studied in 507 unrelated individuals representative of the adult population of Rochester, MN. Analyses are presented separately for females and males. Each lipid and apolipoprotein trait exhibited at least one Apo E genotype-specific regression relationship with the concomitants investigated in this study. In most cases the heterogeneity of regression was associated with differences between the epsilon 32 and epsilon 33 genotype. This study documents that the influence of Apo E genotype on average levels of plasma lipids and apolipoproteins varies among subdivisions of the population defined by age, body size, and smoking status. PMID- 1463014 TI - Characteristics of polymorphism at a VNTR locus 3' to the apolipoprotein B gene in five human populations. AB - We have analyzed the allele frequency distribution at the hypervariable locus 3' to the apolipoprotein B gene (ApoB 3' VNTR) in five well-defined human populations (Kacharis of northeast India, New Guinea Highlanders of Papua New Guinea, Dogrib Indians of Canada, Pehuenche Indians of Chile, and a relatively homogeneous Caucasian population of northern German extraction) by using the PCR technique. A total of 12 segregating alleles were detected in the pooled sample of 319 individuals. A fairly consistent bimodal pattern of allele frequency distribution, apparent in most of these geographically and genetically diverse populations, suggests that the ApoB 3' VNTR polymorphism predates the geographic dispersal of ancestral human populations. In spite of the observed high degree of polymorphism at this locus (expected heterozygosity levels 55%-78%), the genotype distributions in all populations (irrespective of their tribal or cosmopolitan nature) conform to their respective Hardy-Weinberg predictions. Furthermore, analysis of the congruence between expected heterozygosity and the observed number of alleles reveals that, in general, the allele frequency distributions at this locus are in agreement with the predictions of the classical mutation-drift models. The data also show that alleles that are shared by all populations have the highest average frequency within populations. These findings demonstrate the potential utility of highly informative hypervariable loci such as the ApoB 3' VNTR locus in population genetic research, as well as in forensic medicine and determination of biological relatedness of individuals. PMID- 1463015 TI - The gene for familial Mediterranean fever in both Armenians and non-Ashkenazi Jews is linked to the alpha-globin complex on 16p: evidence for locus homogeneity. AB - Familial Mediterranean fever (FMF) is a recurrent inflammatory disorder characterized by short episodes of fever, peritonitis, pleuritis, and arthritis. While FMF has been shown to be inherited in an autosomal recessive fashion in both non-Ashkenazi Jews and Armenian families, clinical differences have raised the possibility of genetic heterogeneity. As its pathogenesis is unknown, mapping of the gene for FMF may provide the first objective method for early and accurate diagnosis of this disease. After excluding 45% of the entire human genome, we studied 14 Armenian and 9 non-Ashkenazi Jewish families with FMF and tested linkage with the alpha-globin locus on chromosome 16. Analysis of the PvuII length polymorphism of the 3' HVR (hypervariable region) probe showed significant linkage with the FMF gene (maximum lod score [lodmax] = 9.76 at maximum recombination fraction [theta] = .076). In the Armenians, the lodmax = 3.61 at theta = .10; and for the non-Ashkenazi Jews, lodmax = 6.28 at theta = .06. There was no evidence for genetic heterogeneity between the Armenians and the non Ashkenazi Jews (chi 2 = 1.28; P = .26) or within either ethnic group (chi 2 = .00; P = .50). Thus, the gene for FMF is linked to the alpha-globin complex on chromosome 16p in both non-Ashkenazi Jews and Armenians. PMID- 1463016 TI - Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism. AB - The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformational polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 10 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. PMID- 1463017 TI - Study of large inbred Friedreich ataxia families reveals a recombination between D9S15 and the disease locus. AB - Friedreich ataxia is a neurodegenerative disorder with autosomal recessive inheritance. Precise linkage mapping of the Friedreich ataxia locus (FRDA) in 9q13-q21 should lead to the isolation of the defective gene by positional cloning. The two closest DNA markers, D9S5 and D9S15, show very tight linkage to FRDA, making difficult the ordering of the three loci. We present a linkage study of three large Friedreich ataxia families of Tunisian origin, with several multiallelic markers around D9S5 and D9S15. Haplotype data were used to investigate genetic homogeneity of the disease in these geographically related families. A meiotic recombination was found in a nonaffected individual, which excludes a 150-kb segment, including D9S15, as a possible location for the Friedreich ataxia gene and which should orient the search in the D9S5 region. PMID- 1463019 TI - Three novel mutations in the liver-type arginase gene in three unrelated Japanese patients with argininemia. AB - Argininemia is caused by a hereditary deficiency of liver-type arginase (E.C.3.5.3.1) and is characterized by psychomotor retardation and spastic tetraplegia. We examined findings in three Japanese patients with argininemia, by using the PCR, cloning, and sequencing procedures. We found three different mutations--G-to-A-365 in exon 4, G-to-C-703 in exon 7, and C-del-842 in exon 8- thereby leading to mutant arginase proteins of W122X, G235R, and L282FS, respectively. Patient 1 was a compound heterozygote, inheriting the allele with G to-A-365 from his mother and the allele with G-to-C-703 from his father. Patients 2 and 3 were homozygotes of the allele with G-to-C-703 and of the allele with C del-842, respectively. Expression tests of these mutant arginases in Escherichia coli indicated that the mutant arginase of W122X did not remain a stable product. The other two mutant arginases--G235R and L282FS--were detected by immunoblot analyses. There was no evidence of activity of the three mutant arginases expressed in E. coli. We tentatively conclude that argininemia is heterogeneous, at the molecular level. PMID- 1463018 TI - Partial isodisomy for maternal chromosome 7 and short stature in an individual with a mutation at the COL1A2 locus. AB - Uniparental disomy for chromosome 7 has been described previously in two individuals with cystic fibrosis. Here, we describe a third case that was discovered because the proband was homozygous for a mutation in the COL1A2 gene for type I procollagen, although his mother was heterozygous and his father did not have the mutation. Phenotypically, the proband was similar to the two previously reported cases with uniparental disomy for chromosome 7, in that he was short in stature and growth retarded. Paternity was assessed with five polymorphic markers. Chromosome 7 inheritance in the proband was analyzed using 12 polymorphic markers distributed along the entire chromosome. Similar analysis of the proband's two brothers established the phase of the alleles at the various loci, assuming minimal recombination. The proband inherited only maternal alleles at five loci and was homozygous at all loci examined, except one. He was heterozygous for an RFLP at the IGBP-1 locus at 7p13-p12. The results suggest that the isodisomy was not complete because of a recombination event involving the proximal short arms of two maternal chromosomes. In addition, the phenotype of proportional dwarfism in the proband suggests imprinting of one or more growth related genes on chromosome 7. PMID- 1463020 TI - Importance sampling. I. Computing multimodel p values in linkage analysis. AB - In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. We propose a Monte Carlo procedure based on the concept of importance sampling, which can be thousands of times more efficient than current procedures. With a reasonable amount of computing time, extremely accurate estimates of the p values can be obtained. Both theoretical results and an example of maturity-onset diabetes of the young (MODY) are presented to illustrate the efficiency performance of our method. Relations between single-model and multimodel p values are explored. The new procedure is also used to investigate the performance of asymptotic approximations in a single model situation. PMID- 1463021 TI - Statement of the American Society of Human Genetics on cystic fibrosis carrier screening. PMID- 1463022 TI - A simple and nonradioactive method for detecting the Rb1.20 DNA polymorphism in the retinoblastoma gene. PMID- 1463023 TI - Amelogenin genes and sexual dimorphism of teeth in humans and mice. PMID- 1463024 TI - Extended electrophoresis resolves the dystrophin gene 5.2-kbp cDMD4-5a/HindIII fragment into two bands. PMID- 1463025 TI - Some lessons from the history of coal workers' pneumoconiosis. PMID- 1463026 TI - Regulation of priority carcinogens and reproductive or developmental toxicants. AB - In California, 370 carcinogens and 112 reproductive/developmental toxicants have been identified as a result of the State's Safe Drinking Water and Toxic Enforcement Act of 1986. They include pesticides, solvents, metals, industrial intermediates, environmental mixtures, and reactive agents. Occupational, environmental, and consumer product exposures that involve these agents are regulated under the Act. At levels of concern, businesses must provide warnings for and limit discharges of those chemicals. The lists of chemicals were compiled following systematic review of published data, including technical reports from the U.S. Public Health Service--National Toxicology Program (NTP), and evaluation of recommendations from authoritative bodies such as the International Agency for Research on Cancer (IARC) and the U.S. Environmental Protection Agency (USEPA). Given the large number of chemicals that are carcinogens or reproductive/developmental toxicants, regulatory concerns should focus on those that have high potential for human exposure, e.g., widely distributed or easily absorbed solvents, metals, environmental mixtures, or reactive agents. In this paper, we present a list of 33 potential priority carcinogens and reproductive/developmental toxicants, including alcoholic beverages, asbestos, benzene, chlorinated solvents, formaldehyde, glycol ethers, lead, tobacco smoke, and toluene. PMID- 1463027 TI - Mortality studies of machining fluid exposure in the automobile industry I: A standardized mortality ratio analysis. AB - Machining fluids are widely used in a variety of common industrial metalworking operations to lubricate and cool both the tool and the working surfaces. Previous studies have suggested elevated respiratory, digestive, and skin cancers in exposed populations. This cohort study was initiated to assess whether long-term exposure to machining fluids in the course of machining, grinding, and other cutting operations is associated with excess cancer mortality. The cohort includes more than 45,000 automobile production workers from 3 plants, almost 1 million years of follow-up, over 10,000 deaths, and an extensive exposure assessment component. Standardized mortality ratios (SMRs) have been estimated for each of the 3 plants, using both U.S. as well as local populations as reference. Relative risks of 1.2-3.1 have been observed for several specific respiratory and digestive cancers of a priori interest, including cancer of the stomach, large intestine, pancreas, lung, and larynx. In addition, elevated risks for leukemia and asthma were noted. Future exposure-response analyses will provide the opportunity to identify relatively modest excesses in cause-specific mortality risk associated with exposure to specific types (straight, soluble, or synthetic), additives, or components of machining fluids. PMID- 1463028 TI - Cancer of the stomach and the colon-rectum among workers in a coke gas plant. AB - Four thousand nine hundred and eight male workers of the Hamburg gas plant, employed for 10 or more years during the period from January 1, 1900 to December 31, 1989, have been traced for cancer mortality. Based on their jobs, they were grouped into three subcohorts: gas furnace workers, workers in other parts of the plant, and white-collar workers. Despite the general "healthy worker effect," gas furnace workers showed a significant incidence of cancer of all sites (standardized mortality ratio [SMR] = 186), particularly cancers of the lung (SMR = 288), stomach (SMR = 177), and the colon-rectum (SMR = 184). In comparison to the death rates of white-collar workers, the manual workers in other parts of the plant also showed an excess of cancer mortality for cancer of these sites. The reason for this excess in cancer mortality seems to be due to the working conditions. The results contribute to the current evidence that exposure to coal carbonization fumes causes not only lung cancer, but also cancers of the stomach and colon-rectum. PMID- 1463029 TI - A case-control study of lung cancer at a dye and resin manufacturing plant. AB - This case-control study evaluated the relationship between lung cancer and occupational factors among employees at a dye and resin manufacturing plant. The study included 51 lung cancer cases and 102 controls who were members of a cohort of workers investigated in a previous retrospective follow-up study. Information on area of employment and on potential exposure to certain chemicals was obtained from plant personnel and medical records and from interviews with long-term employees. Information on potential confounders, including cigarette smoking, was obtained by interviewing study subjects or their next-of-kin. The odds ratio (OR) for heavy smokers compared with light or nonsmokers was 5.9 (95% confidence interval (CI) = 2.4-15). An elevated OR for lung cancer was observed for subjects who worked in the anthraquinone dye and epichlorohydrin manufacturing area of the plant (OR = 2.4; 95% CI = 1.1-5.2) and for employees who were seen at the plant infirmary for acute exposure to chlorine (OR, adjusted for smoking = 27; 95% CI = 3.5-205). Pipefitters employed at the plant for five or more years also had an elevated OR (3.3; 95% CI = 0.8-14). PMID- 1463030 TI - Fluorocarbon 113 exposure and cardiac dysrhythmias among aerospace workers. AB - We investigated the cardiotoxic effects of 1,1,2-Trichloro-1,2,2- Trifluoroethane (fluorocarbon 113 or FC113) exposures among healthy workers cleaning rocket and ground support equipment for the National Aeronautic and Space Administration (NASA) programs. Exposure and ambulatory electrocardiographic (ECG) monitoring data were evaluated on 16 workers, each of whom was examined on exposed and nonexposed workdays. We examined whether there was a greater rate of dysrhythmias on an exposed workday relative to a nonexposed workday. Overall, we found no within subject differences in the rate of ventricular and supraventricular premature beats (number per 1,000 heart beats), fluctuations in the length of the P-R interval, or heart rate. We found that levels of FC113 exposures below the Occupational Safety and Health Administration (OSHA) 8-hour time-weighted-average (TWA) standard of 1,000 ppm did not induce cardiac dysrhythmias or subtle changes in cardiac activity. However, because fluorocarbons may sensitize the heart to epinephrine, this study's negative findings based on sedentary and fairly healthy workers may not be generalizable to other populations of workers who are not as healthy or engaged in more physically demanding work. PMID- 1463031 TI - Outbreak of hypersensitivity pneumonitis among mushroom farm workers. AB - Between April 1982 and August 1985, seven cases of mushroom worker's lung (MWL), a form of hypersensitivity pneumonitis, were diagnosed among workers at one mushroom farm in Florida. The cases suffered from episodic shortness of breath, cough, fever and chills, myalgia, malaise, and difficulty breathing. Pulmonary function testing revealed restrictive ventilatory impairment and reduced diffusing capacity; chest radiographs exhibited diffuse interstitial pulmonary infiltrates. The seven cases occurred among workers from different farm operations, suggesting that workers throughout the farm were exposed to the disease causing agent(s). Six of the affected workers left employment at the farm in order to remain free of symptoms. The other affected worker was able to continue working at the farm, but only by remaining in a maintenance shop which was physically separated from the rest of the farm facilities. An industrial hygiene survey demonstrated that farm workers from every work area were exposed to organic dust constituents suspected of causing MWL, but no specific antigens were identified as the cause of the cases. Of the remaining workers who participated in a cross-sectional respiratory morbidity survey at the farm, approximately 20% of the more heavily exposed workers reported occasionally experiencing symptoms consistent with MWL. Approximately 10% of the workers had below normal spirometry test results, but interpretation was hampered by the diverse racial makeup of the population and lack of an adequate comparison group. No abnormalities consistent with either acute or chronic MWL were seen on the chest radiographs. Serologic tests demonstrated that almost all workers had been exposed to antigens capable of causing MWL, but the results were not associated with health status. At the time of the cross-sectional survey, no workers were found to be suffering acute respiratory problems consistent with MWL. PMID- 1463032 TI - Upper extremity symptoms in supermarket workers. AB - Upper extremity symptoms in supermarket workers, particularly those who performed checking using laser scanners, were evaluated using a questionnaire administered by trained interviewers to 124 supermarket workers. Summary indices of exposure (short-term and long-term) as well as indices of past personal illnesses and personal activities were employed. Outcome data were summarized by four composite symptom indices. Chi square and logistic regression analyses demonstrated that hours of checking work in the preceding 2 weeks and cumulative weighted years of work were associated with adverse upper extremity symptoms. Symptoms involved both the proximal and distal parts of the upper extremities. PMID- 1463033 TI - A mortality study of workers at seven beryllium processing plants. AB - The International Agency for Research on Cancer (IARC) has found that the evidence for the carcinogenicity of beryllium is sufficient based on animal data but "limited" based on human data. This analysis reports on a retrospective cohort mortality study among 9,225 male workers employed at seven beryllium processing facilities for at least 2 days between January 1, 1940, and December 31, 1969. Vital status was ascertained through December 31, 1988. The standardized mortality ratio (SMR) for lung cancer in the total cohort was 1.26 (95% confidence interval [CI] = 1.12-1.42); significant SMRs for lung cancer were observed for two of the oldest plants located in Lorain, Ohio (SMR = 1.69; 95% CI = 1.28-2.19) and Reading, Pennsylvania (SMR = 1.24; 95% CI = 1.03-1.48). For the overall cohort, significantly elevated SMRs were found for "all deaths" (SMR = 1.05; 95% CI = 1.01-1.08), "ischemic heart disease" (SMR = 1.08; 95% CI = 1.01 1.14), "pneumoconiosis and other respiratory diseases" (SMR = 1.48; 95% CI = 1.21 1.80), and "chronic and unspecified nephritis, renal failure, and other renal sclerosis" (SMR = 1.49; 95% CI = 1.00-2.12). Lung cancer SMRs did not increase with longer duration of employment, but did increase with longer latency (time since first exposure). Lung cancer was particularly elevated (SMR = 3.33; 95% CI = 1.66-5.95) among workers at the Lorain plant with a history of (primarily) acute beryllium disease, which is associated with very high beryllium exposure. The lung cancer excess was not restricted to plants operating in the 1940s, when beryllium exposures were known to be extraordinarily high. Elevated lung cancer SMRs were also observed for four of the five plants operating in the 1950s for workers hired during that decade. Neither smoking nor geographic location fully explains the increased lung cancer risk. Occupational exposure to beryllium compounds is the most plausible explanation for the increased risk of lung cancer observed in this study. Continued mortality follow-up of this cohort will provide a more definitive assessment of lung cancer risk at the newer plants and among cohort members hired in the 1950s or later at the older plants. Further clarification of the potential for specific beryllium compounds to induce lung cancer in humans, and the possible contribution of other exposures in specific processes at these plants, would require a nested case-control study. We are currently assessing whether available industrial hygiene data would support such an analysis. PMID- 1463034 TI - Coal workers' pneumoconiosis: a historical perspective on its pathogenesis. AB - The earliest observations on coal workers' pneumoconiosis identified fundamental factors and posed particular problems in its genesis. Among the former, intensity of exposure and particle size were recognized, while argument commenced on the roles of stone dust, thus anticipating the quartz question, and of complicating pulmonary states, which introduced the idea of infection. Major studies of the disease were precipitated by its greatly increased prevalence, which became evident among South Wales coal workers from the 1930s. The principal directions of enquiry remained the same as in Scotland a century before, namely the components of coal mine dust responsible for fibrosis and the additional factor required for the development of massive fibrosis. The combined human and experimental evidence now makes possible conclusions in which confidence may be placed. PMID- 1463035 TI - Racial differences in the prevalence of intraocular lens implants in the United States. AB - We generated population-based estimates of the prevalence of intraocular lens implants by using the 1988 Medical Device Implant Supplement to the National Health Interview Survey. This national survey of a probability sample of the civilian noninstitutionalized United States population comprised 47,485 households and 122,310 persons. To produce national projections, we used survey respondent-reported data based on 1,941 reported intraocular lenses in 1,337 persons. Projected to the United States population, an estimated 2.6 million people had a total of 3.8 million lens implants. The predominant reason for the implant was cataract. The intraocular lens replacement rate was 0.9%. The use of intraocular lens implants was statistically significantly different from the general population in persons with the following socioeconomic characteristics: age (65 years or older), race (white), gender (female), annual family income (less than $20,000, although more commonly at or above the poverty threshold), and education (less than high school). The prevalence rates per 1,000 persons according to age were as follows: 0.3 for persons 44 years old or younger, 9.9 for persons 45 to 64 years old, 33.3 for persons aged 65 to 69 years, 63.5 for persons aged 70 to 74 years, and 113.5 for persons 75 years old or older.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463036 TI - 11-0 mersilene as running suture for penetrating keratoplasty. AB - We evaluated astigmatic results and complications of the combined suturing technique in penetrating keratoplasty by using 11-0 Mersilene as a running suture. Twenty-seven grafts were studied for a follow-up that ranged between ten and 46 months (mean, 27.2 months). During the study, complications included three graft failures, one instance of inadvertent breakage of the running suture, one instance of one suture bite cutting through the recipient cornea, and suture microabscesses in two eyes. Keratometric astigmatism was 2.5 +/- 2.1 diopters at six months, was 2.4 +/- 2.3 diopters at 12 months, and was 2.5 +/- 2.0 diopters at 24 months. Our data indicate that 11-0 Mersilene is suitable for the running suture in corneal transplants in the combined technique. Spontaneous suture dissolution did not occur throughout the follow-up period. The use of a less biodegradable suture enables the maintenance of low levels of astigmatism for longer periods when compared with a previous study that used 11-0 nylon suture. PMID- 1463037 TI - Surgical management of myokymia of the superior oblique muscle. AB - In the past 15 years, we have examined 20 patients in whom myokymia of the superior oblique muscle was diagnosed. Medical treatment (carbamazepine) failed in three patients, and one patient did not accept drug therapy. These four patients (20%) were operated on for persistent oscillopsia and diplopia. One patient underwent only a superior oblique muscle myotomy, but required an inferior oblique muscle myectomy six months later because of iatrogenic superior oblique muscle palsy. The other three patients underwent simultaneous superior oblique muscle myotomy and inferior oblique muscle myectomy. The symptoms resolved postoperatively in all four patients. Symptomatic patients with superior oblique muscle myokymia in whom medical treatment fails or is intolerable can benefit from surgical treatment consisting of combined superior oblique muscle/inferior oblique muscle myectomy. PMID- 1463038 TI - Intraocular fluid cultures after primary pars plana vitrectomy. AB - To determine what organisms enter the eye and remain in the eye after pars plana vitrectomy, vitreous cavity aspirates were cultured postoperatively. Two of 33 (6%) consecutive eyes undergoing primary pars plana vitrectomy had positive cultures. One sample grew a single colony of Staphylococcus epidermidis, the second grew two colonies of Acinetobacter lwoffi. Neither of these eyes developed endophthalmitis. This study demonstrates that bacteria enter the eye at a low rate during pars plana vitrectomy and that the eye on which a vitrectomy has been performed is capable of clearing a low inoculum of bacteria. PMID- 1463039 TI - Criteria to detect minimal expressivity within families with autosomal dominant aniridia. AB - Autosomal dominant aniridia with complete penetrance without Wilms' tumor in five generations with 27 affected family members has been reassigned from chromosome 2p25 to chromosome 11p13. Clinically, aniridia was obvious in affected individuals with variable expressivity when they had rudimentary iris stumps, typical or atypical iris colobomata, or round, eccentric pupils. However, iris and retinal fluorescein angiography was required to detect abnormal vascular remodeling that resulted in incomplete iris collarettes and decreased retinal foveal avascular zones in 27 family members at risk with round, central pupils. These angiograms distinguished five affected and 22 unaffected individuals, and were the critical criteria required to detect minimal expressivity of aniridia in family members with round, central pupils. PMID- 1463040 TI - Causes of reduced visual acuity on long-term follow-up after cataract extraction in patients with uveitis and juvenile rheumatoid arthritis. AB - We reviewed the long-term follow-up on a consecutive series of 16 eyes from ten patients with juvenile rheumatoid arthritis-associated cataracts that were removed by using pars plana lensectomy and vitrectomy. All patients had prominent cataracts, chronic uveitis, posterior synechiae, and vitreitis preoperatively, and had at least 12 months of follow-up postoperatively. The median length of follow-up was 51 months (range, 12 months to ten years). In the early postoperative period, a visual acuity of 20/70 or better was obtained in 13 of 16 eyes (81%). With longer follow-up, the final visual acuity was 20/70 or better in only nine of 16 eyes (56%). The primary categories of delayed visual loss in these cases were glaucoma and macular disease (chronic cystoid macular edema, macular hole, hypotony maculopathy, and recurrent macular pucker). Despite these limitations in maintaining good visual acuity, a pars plana lensectomy and vitrectomy approach is effective for cataracts in these patients with uveitis. PMID- 1463041 TI - Prediction of visual recovery after scleral buckling of macula-off retinal detachments. AB - Patients with rhegmatogenous retinal detachments involving the fovea have visual loss that may not be recoverable despite anatomically successful surgery. Few guidelines exist to predict ultimate visual outcome with any certainty. We found that despite macular detachment, a device commonly used to predict visual acuity in cataractous eyes, the Potential Acuity Meter (Mentor O & O, Inc., Norwell, Massachusetts), provided acuity measurements even when Snellen visual acuity levels were poor or unmeasurable. In a study of 50 consecutive patients with clear media, we investigated a possible correlation between postoperative Snellen visual acuity with the preoperative Potential Acuity Meter results. We found that actual visual improvement correlated well with potential visual improvement as determined by Potential Acuity Meter measurements (R = .92). Preoperative assessment of patients with this device was a better predictor of final visual outcome than preoperative Snellen visual acuity, the extent of retinal detachment, or the duration of the retinal detachment by history. PMID- 1463042 TI - Prevalence and risk factors of diabetic retinopathy among noninsulin-dependent diabetic subjects. AB - In a population-based study in Taiwan, 11,478 subjects aged 40 years or older were screened for diabetes in one urban and five rural areas. Among the 715 subjects proven to have diabetes, 527 subjects underwent ophthalmoscopy. Diabetic retinopathy was present in 184 of the 527 subjects (35.0%), including background diabetic retinopathy in 157 subjects (30.0%), preproliferative diabetic retinopathy in 15 subjects (2.8%), and proliferative diabetic retinopathy in 12 subjects (2.2%). Diabetic retinopathy was correlated with the duration of diabetes and age at onset of diabetes, type of diabetes treatment, higher serum creatinine levels, and lower serum cholesterol levels. Several other factors, including gender, age, residential area, family income, educational level, control and family history of diabetes, body mass index, physical activity, exercise, cigarette smoking, stroke, ischemic heart disease, leg vessel disease, hypertension, and proteinuria, had no significant association with retinopathy. By multiple logistic regression analysis, duration of diabetes was the most important risk factor related to retinopathy. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control (relative risk, 1.57; .05 < P < .10). The univariate analysis disclosed that proliferative diabetic retinopathy was related to older age at examination, older age at onset of diabetes, type of diabetes treatment, and presence of leg vessel disease. Insulin-treated diabetic subjects also had a higher risk of proliferative diabetic retinopathy than patients in whom diabetes was controlled by diet, with a relative risk of 2.51 (.05 < P < .10) in the multiple logistic regression analysis. PMID- 1463043 TI - Cytokines in the vitreous of patients with proliferative diabetic retinopathy. AB - Sixteen vitreous and paired serum samples from 13 patients with proliferative diabetic retinopathy, vitreous samples from seven cadaveric control subjects, and aqueous humor samples from 15 normal control subjects were assayed for the cytokines interleukin-1, tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Interleukin-6 was detected in 15 of 16 vitreous samples (94%) from diabetic patients, but it was not detected in any of the aqueous humor samples. Vitreous interleukin-6 levels positively correlated with ocular disease activity. Interleukin-1 was detected in seven of 16 vitreous samples (44%) and in four of ten aqueous humor samples (40%), whereas tumor necrosis factor-alpha and interferon-gamma were never detected in vitreous or aqueous fluid. Serum samples from diabetic patients and control subjects contained comparable low levels of interleukin-6. Interleukin-1, tumor necrosis factor-alpha, and interferon-gamma were not found in any of the sera. Because interleukin-6 can function as B-cell differentiation factor, this cytokine may have a role in immunoglobulin deposition in the ocular tissues and in the immunopathologic characteristics of proliferative retinopathy. PMID- 1463044 TI - Results of intraoperative 5-fluorouracil supplementation on trabeculectomy for open-angle glaucoma. AB - The success rate of filtration surgery has been increased by the postoperative subconjunctival injection of 5-fluorouracil, a potent antimetabolite. However, the optimal route of administration has not been determined. Trabeculectomy was performed on one eye each of 14 patients. Topical 5-fluorouracil was applied intraoperatively (50 mg/ml for five minutes) and subconjunctival 5-fluorouracil was injected postoperatively (an average of 5.8 injections) (mean total dose, 29 mg). Seven of the 14 eyes had primary open-angle glaucoma, and seven eyes had open-angle glaucoma with either uveitis, aphakia, or previous failed trabeculectomy. Mean preoperative intraocular pressure was 24.7 mm Hg during treatment with an average of three antiglaucoma medications, and mean final intraocular pressure was 11.9 mm Hg during treatment with an average of 0.2 medication. Thirteen of 14 eyes (93%) had final intraocular pressure of 18 mm Hg or less. Mean follow-up was 6.4 months (range, four to nine months). No remarkable complications occurred. Visual acuity remained stable in 13 of 14 eyes (93%). Intraoperative 5-fluorouracil may be a helpful adjunct in achieving low final intraocular pressure after trabeculectomy. PMID- 1463045 TI - Ultrastructural findings in an autopsy eye from a patient with Usher's syndrome type II. AB - We studied an eye taken at autopsy from a 55-year-old woman with retinitis pigmentosa and partial deafness (Usher's syndrome type II). Two years before her death, her visual acuity was R.E.: 20/80 and L.E.: 20/50, and visual fields were constricted to a 30- to 40-degree diameter with a V4e white test light. Both rods and cones were present across the retina except for areas of the midperiphery; remaining photoreceptors had shortened or disrupted outer segments, or both, and some cones had inclusion bodies in inner segments. In the macula, most of the connecting cilia of photoreceptors appeared abnormal, with either extra microtubules or an apparent disruption of the nexin link between doublet microtubules. The pigment epithelium was abnormal across the eye, with diminished apical microvilli and basal infoldings of the plasma membrane. Possible mechanisms by which abnormal cilia could lead to photoreceptor cell death are considered. PMID- 1463046 TI - Visual field defects in patients with normal-tension glaucoma and patients with high-tension glaucoma. AB - We compared the automated visual field test results of 24 patients with normal tension glaucoma and 24 patients with high-tension glaucoma who were closely matched for the amount of visual field loss to determine any differences in the characteristics of visual field defects between the two groups. Patients were matched with a maximum allowable difference in mean deviation of 0.3 dB. Although the normal-tension group had a greater amount of focal visual field loss (pattern standard deviation), the difference was not statistically significant (P = .628). Additionally, there was no statistically significant difference in the amount of diffuse or focal visual field damage in the superior hemifields between the two groups; however, the patients with normal-tension glaucoma had a significantly greater amount of localized visual field loss in the inferior hemifield than the patients with high-tension glaucoma (P = .015). Our data support the hypothesis that a vascular mechanism may have a greater role in the pathogenesis of optic nerve damage and visual field loss in patients with normal-tension glaucoma than in patients with high-tension glaucoma. PMID- 1463047 TI - Low-tension glaucoma in identical twins. PMID- 1463048 TI - Impending macular hole associated with topical pilocarpine. PMID- 1463049 TI - The association of iridoschisis and angle-recession glaucoma. PMID- 1463050 TI - Vitreous pulsations, relative hypotony, and retrobulbar cyst associated with a congenital optic pit. PMID- 1463051 TI - Spontaneous retinal reattachment in a patient with persistent hyperplastic primary vitreous and an optic nerve coloboma. PMID- 1463052 TI - Late-onset sterile endophthalmitis after Molteno tube implantation. PMID- 1463053 TI - Bilateral panuveitis, sebopsoriasis, and secondary syphilis in a patient with acquired immunodeficiency syndrome. PMID- 1463054 TI - Bilateral radiant damage to the cornea and retina after exposure to a 700-V electric discharge. PMID- 1463055 TI - Parabulbar anesthesia. PMID- 1463056 TI - Causes and prognosis in 4,278 cases of paralysis of the oculomotor, trochlear, and abducens cranial nerves. PMID- 1463057 TI - Sudden retinal manifestations of intranasal cocaine and methamphetamine abuse. PMID- 1463058 TI - Confusion in occupational therapy research: does the end justify the method? PMID- 1463059 TI - Cross-cultural assessment of process skills. AB - A standardized activities of daily living evaluation that has acceptable psychometric qualities, can relate discrete component skills to functional performance, includes culture-relevant test items, is standardized on culture specific samples, and is free of cultural bias is needed to evaluate diverse cultural populations. The Assessment of Motor and Process Skills (AMPS) (Fisher, 1990a) offers a unique solution. The AMPS consists of 35 motor and process skill items assumed to represent two universal taxonomies that are free of cultural bias. The study described in this paper focused on the 20 process skill items of the AMPS process skills scale. To test the hypothesis that the AMPS process skills scale is suitable for cross-cultural applications, a translation of the AMPS was calibrated on a group of 20 Taiwanese subjects. The validity and reliability of the AMPS process skills scale were examined when applied to this sample. Examination of reliability included the extent to which rater scoring remained stable over time. The results revealed that the AMPS process skills scale has high intrarater reliability and is valid when applied to young nondisabled Taiwanese subjects. The results suggested that the AMPS could be applied to Taiwanese samples. However, further investigation is needed to determine whether Taiwanese activities can be calibrated onto the same scale as North American activities to make a single cross-cultural AMPS. PMID- 1463060 TI - Deficits of reaching in subjects with left hemiparesis: a pilot study. AB - Therapy to restore functional movement of stroke patients is based on assumptions about the deficits that occur in motor control as a result of stroke. Success has been limited, perhaps as a result of insufficient information concerning the characteristics of movement after stroke. In this pilot study, the Waterloo Spatial Motion Analysis Recording Technique (WATSMART), an optoelectric motion analysis system, was used with surface electromyography to measure voluntary reaching in the impaired and unimpaired arms of 5 subjects with left hemiparesis. The ability to reach in a smooth coordinated way was significantly poorer in the impaired arms than in the unimpaired arms, for which scores were essentially normal. The patients were less able to activate the muscles of the impaired arm and, as a result, used a greater percentage of the maximum activity they could generate to complete the unresisted reaching task. The electromyographic differences between arms, however, did not reach significance. The results corroborate previous findings and show that movement deficits of particular patients can be diagnosed precisely with kinematic analysis and electromyography. If greater precision in diagnosis were available clinically, more effective therapy might be developed. PMID- 1463061 TI - Fine motor activities in elementary school: preliminary findings and provisional implications for children with fine motor problems. AB - This study was designed to obtain a detailed picture of the fine motor requirements in regular elementary school classrooms. This knowledge is critical for occupational therapists in working with children with fine motor and handwriting problems who are main-streamed into regular classes. The allocation of time to fine motor activities and the types of fine motor tasks children are expected to perform in elementary school were investigated through the observation of six elementary school classrooms. A written minute-by-minute record of one whole day's activities in each classroom showed that 30% to 60% of the day was allocated to fine motor activities, with writing tasks predominating over other manipulative tasks. Implications for children with fine motor difficulties include the need for modifications to volume of work, types of tasks, and materials. PMID- 1463062 TI - Activity positioning and ischial tuberosity pressure: a pilot study. AB - Ipsilateral ischial tuberosity pressure of 12 subjects seated in wheelchairs was measured during reach to an activity positioned on both an upright and a flat plane. Ischial tuberosity pressure during cross-body, forward, and lateral reach was measured with a static pressure measurement device. Differences between flat plane readings and upright-plane readings were analyzed with a t test; no significant difference was obtained. A repeated-measures analysis of variance revealed significant differences in ischial tuberosity pressure between cross body, forward, and lateral reach in the flat plane activity. However, no significant difference was found between cross-body, forward, and lateral reach in the upright-plane activity. Results of this study support the theory that forward and lateral positioning of activity can supplement standard techniques for relieving pressure. PMID- 1463063 TI - Effects of linear vestibular stimulation on body-rocking behavior in adults with profound mental retardation. AB - The effects of linear vestibular stimulation on body-rocking behaviors in adults with profound mental retardation were studied. A single-system multiple base-line design across 3 subjects was used. The design included three phases spread over a period of 9 weeks. An interval time sampling procedure was used to collect data. Data from the 3 subjects were graphed and interpreted through visual inspection. Trend lines were computed with the celeration line approach to supplement the visual inspection of the data. The results demonstrated a decrease in body rocking behaviors during the treatment and follow-up phases for Subject 2 but no obvious change in performance for Subjects 1 and 3. A lengthier treatment period and selection of subjects with similar body-rocking frequencies are suggested for further research. PMID- 1463064 TI - Occupational adaptation: toward a holistic approach for contemporary practice, Part 2. AB - This paper introduces a practice model based on the occupational adaptation frame of reference (Schkade & Schultz, 1992). The occupational adaptation practice model emphasizes the creation of a therapeutic climate, the use of occupational activity, and the importance of relative mastery. Practice based on occupational adaptation differs from treatment that focuses on acquisition of functional skills because the practice model directs occupational therapy interventions toward the patient's internal processes and how such processes are facilitated to improve occupational functioning. The occupational adaptation practice model is holistic. The patient's occupational environments (as influenced by physical, social, and cultural properties) are as important as the patient's sensorimotor, cognitive, and psychosocial functioning and the patient's experience of personal limitations and potential is validated. The integration of these concepts drives the treatment process. Through a description of treatment with a variety of patients, this paper presents the model's diversity and illustrates the relationship between the concepts. The occupational adaptation practice model reflects the uniqueness of occupational therapy and integrates the profession's historical practice with contemporary interventions and methods. PMID- 1463065 TI - Clinical reasoning process for service provision in the public school. AB - This paper outlines the clinical reasoning process used to guide decisions on the provision of occupational therapy services in the Wake County Public School System in North Carolina. The process is based on a theoretical framework derived from occupational therapy theory and public law. Benefits of using the clinical reasoning process include (a) increased consistency of decision making among therapists; (b) increased appropriateness of decisions regarding whether a student needs educationally based occupational therapy services, what type of occupational therapy service would meet the student's need, and how often this service should be provided; and (c) improved ability of therapists to articulate to all those involved with a student the reasoning behind decisions to provide educationally based occupational therapy services. The schematic diagrams that depict this process provide a useful tool for therapists with varied work experiences entering school-based practice. PMID- 1463066 TI - Continuing education requirements to maintain occupational therapy licensure. AB - Different states use a variety of regulatory mechanisms to monitor the quality of practice in occupational therapy. The requirement for mandatory continuing education has been adopted by fewer than half of American states, but there is reason to predict that this trend will increase. This study investigates the patterns linking licensure to continuing education and recommends actions to ensure uniformity and accountability. PMID- 1463067 TI - Diet manipulation to resume regular food consumption for an adult with traumatic brain injury. PMID- 1463069 TI - Ethics in evaluation in occupational therapy. PMID- 1463068 TI - Pediatric rehabilitation: clinical judgment regarding treatment intensity. PMID- 1463070 TI - Music perhaps best used by music teachers. PMID- 1463071 TI - Recovering relationships: a feminist analysis of recovery models. AB - Two models of recovery based on the concepts of independence and interdependence are contrasted from a feminist perspective. Drawing on social and psychological analyses, the authors critique the overemphasis of independence as the goal of health care and instead advocate a more relational model of therapy that reinforces social and emotional connections between people. Two narratives from occupational therapy are used to illustrate the differing assumptions underlying these models. The authors discuss some of the structural and interactional barriers to the expression of interdependence in health care institutions. They suggest that through purposefully sharing practice experiences and instating collaborative, nonhierarchical models of organization, practitioners can begin to overcome these barriers. PMID- 1463072 TI - Gender differences in dementia management plans of spousal caregivers: implications for occupational therapy. AB - Occupational therapists treating older people with Alzheimer disease know that they must also consider the others who are affected by the disease, the informal caregivers. Intervention is most effective when it enables both the impaired person and the primary caregiver to manage the secondary symptoms of dementia. Unfortunately, little is understood about how caregivers approach and carry out their tasks and about why male and female caregivers respond differently to their caregiving role in terms of depression, burden, stress, and substance abuse. This paper discusses the effects of gender on dementia management plans of spousal caregivers. Husbands and wives have different approaches to caregiving; each approach has consequences. Male caregivers adopt a task-oriented approach to their duties and carry out their activities in a linear fashion; female caregivers use a parent-child approach and nest activities inside one another in a constant stream of work. Two cases are presented to illustrate gender differences in dementia management plans. Implications for occupational therapy include suggestions for supporting men and women in their caregiving role, modulating the negative consequences of caregiving, and conducting research to demonstrate the efficacy of an occupational therapy approach. PMID- 1463073 TI - Interwoven threads: occupational therapy, feminism, and holistic health. AB - Occupational therapy is a predominantly female profession; 93% to 95% of occupational therapists are women. The implications and ramifications of this reality have seldom been directly addressed. In this article, beliefs about balance, activity, environment, and autonomy are explored from the perspectives of occupational therapy, feminism, holistic health, and medicine. The assertion that occupational therapy has more in common philosophically with feminism and holistic health than it does with medicine is supported. This awareness provides a new framework for examining current issues of concern to the profession, such as support for purposeful activity, existence outside the mainstream of power holders, and problems and powers inherent in being seen as a women's profession. Recommendations are made that occupational therapists commit more money and energy to encourage, facilitate, and support female leadership; develop innovative strategies for keeping members who take time out to raise families informed; support more holistic and feminist reorganization of work settings; instill awareness of these issues in our students; and address our strengths as a women's profession. All occupational therapists must also confront their own anti women prejudice. PMID- 1463074 TI - Women, HIV infection, and AIDS: tapestries of life, death, and empowerment. AB - Women, the minority population in the human immunodeficiency virus (HIV) pandemic, are fast becoming one of the highest subgroups to be infected and affected by the disease. In the United States, most of these women are black or Hispanic, poor and urban dwellers, and addicted to drugs. This paper discusses the physical, psychological, and social manifestations of HIV disease in women, such as diminished activity tolerance, neurologic or cognitive changes, occupational and social role imbalance, and stigma and discrimination, and describes the sociocultural aspects of women's lives for assessment and treatment of women with HIV. Health promotion, education, and AIDS prevention and wellness programming are emphasized as strategies toward facilitation of self-empowerment for women with HIV disease. These health promotion and wellness strategies include learning of new and adaptation of current roles; learning strategies for self-care that include care for one's physical, psychosocial, spiritual, and sexual health; and learning and developing action plans toward healthy living and self-empowerment. PMID- 1463075 TI - Embracing our past, informing our future: a feminist re-vision of health care. AB - Using a feminist perspective, this paper explores the roots of the practice of healing and medicine. It traces the role of women in health care from prehistorical times, through the present, and into the future discussing the changing paradigms that the author identifies as (a) the Prototypic Paradigm: Mysticism and Healing; (b) the Scientific Paradigm: Curing; and (c) the Paradigm of Inclusion: Caring, Curing, and Healing. The role and status of women in society are reflected within these paradigms, and the changing status of the profession of occupational therapy is discussed within this framework. The unique skills and contributions of occupational therapy more closely fit within the Paradigm of Inclusion and can support us as health care leaders within the changing world of the 21st century. PMID- 1463076 TI - Aging profession, enlightened professionals? PMID- 1463077 TI - Motherhood, occupational therapy, and feminism: weaving or unraveling the fibers of our lives? PMID- 1463078 TI - Proud and visible as occupational therapists. PMID- 1463079 TI - Supports specialization in occupational therapy and use of physical agent modalities. PMID- 1463080 TI - We need research on psychosocial occupational therapy. PMID- 1463081 TI - Feminism: an inclusive perspective. PMID- 1463082 TI - A mother's work: two levels of feminist analysis of family-centered care. AB - The following case describes 5 years of a mother's care for her child with multiple chronic conditions, in the neonatal intensive care unit and at home. Because caregiving is primarily a female activity, a feminist approach is used. This mother's efforts on behalf of her son show how work within the domains of direct medical care, normal mothering care, coordination of equipment and supplies and professionals, and synthesis of meaning emanated from her definition of motherhood. The case suggests interventions in family-centered care, offers an examination of two levels of feminist analysis for their usefulness to occupational therapy, and provides an opportunity to examine the topic of motherhood within feminism. PMID- 1463083 TI - A woman's place: unpaid work in the home. AB - Household work has only recently become a valid topic of study. Feminist scholars were among the first social scientists to draw attention to women's unpaid work in the home. Although household work occupations are frequently used for assessment and treatment within practice, occupational therapy literature demonstrates a paucity in the area of these occupations. This review of the feminist literature summarizes theory and research that explore the historical, political, social, and personal meanings of household work. Feminist analysis of household work may sensitize occupational therapists to the complex interactions of these meanings and lead them to the realization that women's responsibility for unpaid work in the home may have repercussions in the daily lives of both women and men. PMID- 1463084 TI - Opening feminist histories of occupational therapy. AB - This paper frames the history of occupational therapy in feminist terms. It focuses on gender segregation in occupational therapy, the influence of class and race in shaping opportunities for occupational therapists, and the place of feminism in the goals and achievements of the occupational therapy profession. Such issues have been addressed by feminist scholars in histories of women in medicine, nursing, and other helping professions. These sources help place the achievements of occupational therapy within the context of women's historic entry and advancement in the American work force. PMID- 1463085 TI - Shanidar 1: a case of hyperostotic disease (DISH) in the middle Paleolithic. AB - The Shanidar 1 Neandertal partial skeleton presents osteophytic lesions on its vertebrae and appendicular skeleton which appear independent of the multiple traumatic and degenerative joint disease lesions on the individual. In particular, the large flowing osteophyte on the L3 body, a smaller one on the L5 body, and enthesopathic osteophytes on both calcaneal tuberosities, both patellae and the left ulnar olecranon, support a diagnosis of hyperostotic disease (DISH). The diagnosis is supported by small enthesopathic osteophytes on the preserved femoral greater trochanter and scapular corocoid process. This diagnosis would make it the oldest hominid specimen clearly presenting this systemic condition. PMID- 1463086 TI - Obstetric dimensions of the true pelvis in a medieval population from Sudanese Nubia. AB - Functional analysis of the true pelvis (defined as that portion lying below and including the pelvic brim) was undertaken on a sample of 36 females from the Medieval site of Kulubnarti in Sudanese Nubia. Standard obstetric measurements were taken and compared to four additional prehistoric skeletal samples and to modern American standards for the same obstetric dimensions. Relative to the other prehistoric populations, the Kulubnarti pelves are smaller in most dimensions and, when compared to modern American standards, from one-third to one half would be diagnosed as contracted in one or more planes. Given the meager, fluctuating resources of these Medieval Nubians' harsh desert environment, pelvic size reduction is a likely result of body size reduction as one biological response to nutritional stress (Mittler and Van Gerven, 1989; Moore et al., 1986; Van Gerven et al., 1981). It is argued, however, that size reduction created a high potential for either maternal-neonatal morbidity and mortality due to fetopelvic disproportion or neonatal loss due to low birth weight. In either case, it is suggested that the Kulubnarti population paid a significant biological price for this aspect of size reduction. PMID- 1463087 TI - Evaluation of the obstetric significance of some pelvic characters in an 18th century British sample of known parity status. AB - The excavations at Christ Church, Spitalfields (1984-86) produced a sample of 968 human skeletons which were interred between 1729 and 1859. Of these, 387 were recovered in association with coffin plates stating name, age at death, and date of death. There are 138 adult females in the named sample and the obstetric histories of 94 have been reconstructed from historical documentation. Such variables as birth spacing, number of children, and age at first and last births are known for the majority of this sample. Any individual about whose history there is any doubt has been excluded from the analysis. A middle-class group, they were largely of high nutritional status and, by the standards of the day, lived in sanitary and comfortable conditions. Both males and females have a mean age at death of 56 years. The presence or absence, the typology, the severity, the width and the length of the preauricular sulcus, the presence or absence and the number of pits on the dorsal aspect of the pubic body, sulci along the anterior sacrum adjacent to the auricular facet, and the extension of the pubic tubercle were evaluated in relation to the obstetric histories of these females. Statistical analysis has demonstrated a relationship between the presence of pubic tubercle extension and parity status and between the degree of extension and the number of children borne (P < .02). Statistically there is no significant relationship (P > .05) between either the preauricular sulcus or pubic pitting and parity status. Sacral scarring is significantly associated (P < .05) with parity status, but as it was evident in only eight females it has little practical application. Sample sizes are small, and it must be considered that statistical evaluation of larger samples might detect associations between variables not demonstrated here. There is no significant relationship between any of the cortical variants under consideration and age at death. PMID- 1463088 TI - Gene geography of South America: testing models of population displacement based on archeological evidence. AB - Gene frequencies for 13 marker systems are used to construct synthetic gene frequency maps of South America. The surfaces generated using the first three principal components exhibit clines which validate models of population displacement based on archeological data and a previous analysis of craniometrical variation. PMID- 1463089 TI - Longitudinal analysis of adolescent growth of ladino and Mayan school children in Guatemala: effects of environment and sex. AB - The rate of growth in height and the timing of adolescent growth events are analyzed for two samples of Guatemalan children. One sample includes Mayan school children, 33 boys and 12 girls between the ages of 5.00 to 17.99 years, living under poor conditions for growth and development. The second sample includes ladino children, 78 boys and 85 girls of the same age range, living under favorable conditions for growth. The Preece-Baines model I function is used to estimate mean values for rates and timing of childhood and adolescent growth events for the two groups. Significant statistical contrasts (t-tests) of these means show Mayan boys reach the age of "take-off" (TO; the onset of the adolescent growth spurt) 1.45 years later, achieve peak height velocity (PHV) 1.68 years later, and continue growing for about 2.0 years longer than do the ladino boys. Despite the Mayan boys' increased duration for growth they grow significantly more slowly than the ladinos. Mayan boys are 6.60 cm shorter than ladinos at the age of TO and are estimated to be 7.71 cm shorter than the ladinos at adulthood. Mayan girls reach the age of TO 0.93 years later than do the ladina girls, but the two groups do not differ in the age at PHV or the age at adulthood. The mean height of Mayan girls is significantly less than that of ladinas at the age of TO (6.5 cm), and this difference increases to an estimated 11.14 cm at adulthood. Possible causes of these ethnic and sex-related differences in amounts and rates of growth are discussed in relation to hypotheses about the genetic and environmental determinants of human development. PMID- 1463090 TI - Cross-cultural analysis of migration rates: effects of geographic distance and population size. AB - A model is developed that treats migration rates among populations as a function of the geographic distance between them and the size of both sources and recipient population. Specifically, mij/mjj = a(Ni/Nj)pe-bd, where mij/mjj is the relative migration rate into population j from population i, Ni is the size of the source population, Nj is the size of the recipient population, d is the geographic distance between populations i and j, p is a measure of differential density-dependence, b is a measure of distance decay, and a is an adjustment parameter with little demographic meaning. Methods of parameter estimation and hypothesis testing using maximum likelihood are outlined. These methods are applied to migration matrix data from 13 samples obtained from the literature representing a wide range of ecological settings. All samples show a significant effect of geographic distance on migration, and all but one show a significant effect of differential population size. All but one sample show an overall tendency for migration to be negative density-dependent; that is, the relative migration rate is greater from larger populations to smaller populations than the reverse. PMID- 1463091 TI - Human marriage systems and sexual dimorphism in stature. AB - Contemporary populations of Homo sapiens are sexually dimorphic on a variety of traits. In terms of stature, men are reliably between 4% and 10% taller than women in well-sampled human populations. Are cross-cultural differences in the magnitude of sexual dimorphism consistent with expectations from sexual selection theory? Prior studies have provided conflicting answers to this question in part because they failed to agree on how the force of sexual selection should or could be operationalized. Here we offer a simple and unbiased method for operationalizing sexual selection and retest two separate predictions from earlier work (Alexander et al., 1979) about its expected impact on stature dimorphism in a sample of 155 societies. Neither prediction matches the observed cross-cultural distribution of dimorphism. However, this is not the consequence of a random distribution of dimorphism across societies. Instead, the data exhibit a robust and unexpected pattern. PMID- 1463092 TI - Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria. AB - Although the categorization of proliferative breast lesions provides valuable information regarding subsequent risk of breast cancer, the ability of pathologists to classify such lesions in a reproducible fashion has not been adequately evaluated. To assess further interobserver reproducibility in the categorization of proliferative breast lesions, six pathologists each reviewed 24 proliferative ductal lesions and classified them as either usual hyperplasia (H), atypical hyperplasia (AH), or carcinoma in situ (CIS). Before evaluation of the study slides, all the participants were instructed to use the diagnostic criteria of Page and co-workers and were provided with both a written summary of these criteria and a set of teaching slides with representative examples of each type of lesion. Complete agreement among all six pathologists was seen in 14 cases (58%); five or more agreed in 17 cases (71%); and four or more arrived at the same diagnosis in 22 cases (92%). No pathologist consistently rendered more "benign" or "malignant" diagnoses than any other. After assigning numerical values for each diagnostic category (H = 1, AH = 2, CIS = 3), the scores for the group of 24 cases did not differ significantly by pathologist (p = 0.68; average score range, 1.7-2.0). Our results indicate that with the use of standardized criteria, interobserver concordance in the diagnosis of proliferative ductal breast lesions can be obtained in the majority of cases. PMID- 1463093 TI - Chondroid chordomas and low-grade chondrosarcomas of the craniospinal axis. An immunohistochemical analysis of 17 cases. AB - The classification of cartilaginous neoplasms of the craniospinal axis is controversial. Indeed, the very existence of chondroid chordomas has recently been questioned. In an effort to clarify the direction of differentiation of cartilaginous neoplasms of this region, 17 neoplasms obtained from 17 patients with cartilaginous tumors of the craniospinal axis were examined by immunohistochemistry with a panel of antibodies. The panel included antibodies to cytokeratin (CK), epithelial membrane antigen (EMA), vimentin (VIM), S-100 protein, carcinoembryonic antigen (CEA), and type II collagen. Areas with cartilaginous differentiation were present in all 17 neoplasms. These areas were characterized by a matrix of amorphous blue ground substance with lacunae that contained enlarged and slightly atypical cells. This cartilaginous matrix stained strongly for type II collagen. Thirteen of the 17 neoplasms had a biphasic growth pattern in which areas with conventional chordoma were admixed with areas with cartilaginous differentiation. The cells within the cartilaginous components of these 13 neoplasms stained for CK (10 of 12 cases), EMA (10 of 13 cases), VIM (12 of 12 cases), S-100 protein (seven of 12 cases), and CEA (two of nine cases). Similarly, the conventional chordoma components of these same 13 neoplasms stained for CK (12 of 12 cases), EMA (13 of 13 cases), VIM (12 of 12 cases), S 100 protein (nine of 12 cases), and CEA (two of nine cases). The hyaline appearing areas between the cords and sheets of cells of the conventional chordoma components of these 13 tumors also stained with type II collagen. These 13 tumors with both neoplastic cartilage and conventional chordoma were classified as chondroid chordomas. One of the 17 cases was composed entirely of neoplastic cartilage; however, the cells within the matrix of the cartilage of this neoplasm stained with the epithelial markers (CK and EMA). Based on the presence of epithelial differentiation within this otherwise cartilaginous neoplasm, it was also classified as a chondroid chordoma. In contrast, the remaining three cases without histologic evidence of chordoma differentiation did not stain for CK or EMA, but they did stain for S-100 protein (three of three cases) and VIM (three of three cases). These three tumors were therefore classified as chondrosarcomas. For purposes of comparison, 19 conventional chordomas without cartilage and 29 peripheral chondrosarcomas were also stained. The 19 conventional chordomas stained in a pattern similar to the conventional chordoma components of the chondroid chordomas, whereas the 29 peripheral chondrosarcomas stained in a pattern similar to the three chondrosarcomas of the craniospinal axis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1463094 TI - Well-differentiated thymic carcinoma. An organotypical low-grade carcinoma with relationship to cortical thymoma. AB - Based on a study of 26 cases, the well-differentiated thymic carcinoma is described as a distinct organotypical carcinoma of the thymus with low-grade malignancy. It is characterized by a predominance of epithelial cells with usually low mitotic rate, an epidermoid differentiation with slight to moderate cytological atypia, the constant presence of interepithelial immature cortical thymocytes, lobular growth, and formation of epithelial palisades around perivascular spaces. The tumor occurs at age 14 to 76 years in both sexes. An association with myasthenia gravis is found in 77% of the patients, and 83% of the tumors show invasion of adjacent organs or endothoracic metastasis at primary operation. This rate is higher than in cortical thymomas (47%) but lower than in other thymic carcinomas (92%). Two of 18 patients with follow-up died of tumor recurrence and pleural metastasis. Well-differentiated thymic carcinoma can be related to cortical thymoma by common morphological features and a similar immunophenotype of epithelial cells. It must be differentiated from the lymphocyte-depleted cortical thymomas after corticosteroid treatment and from the benign epithelial-rich medullary thymomas. PMID- 1463095 TI - Clear cell sarcoma of soft tissues. Mayo Clinic experience with 35 cases. AB - Thirty-five cases of clear cell sarcoma of soft tissues were studied to determine the clinical or morphologic features that are important in predicting prognosis. Tumors occurred most commonly in the extremities, and the majority of the patients were young women. Surgery was the elected treatment in every case. Five patients experienced local recurrences, and metastases developed in 22. Fifty four percent of the patients died of tumor, 11% are alive with disease, and the remaining 34% are alive and well; the average survival for each group was 67 months, 113 months, and 103.5 months, respectively. This sarcoma is characterized by small clusters of polygonal to spindle cells featuring clear to slightly basophilic cytoplasm and vesicular nuclei with prominent nucleoli. The clusters are separated by delicate fibrous septa. In a deletion, clear cell sarcoma has low mitotic activity, little or no necrosis, and mild nuclear pleomorphism. Tumor size and the presence of necrosis are statistically significant predictors of prognosis. All 12 patients with tumors measuring > 5 cm died of disease or are alive with disease. Eleven of the 20 patients with tumors measuring < 5 cm are alive with no evidence of disease. Tumor necrosis was present in 10 cases; eight of these patients died of disease and one is alive with disseminated metastases. PMID- 1463096 TI - Sclerosing inflammatory pseudotumor of the urinary bladder in a child. AB - A case of inflammatory pseudotumor of the urinary bladder in a 2-year-old child is presented. It was characterized by nodular intravesical growth and massive infiltration of the bladder wall. Microscopically, the lesion showed in its largest part a relatively paucicellular spindle cell growth and a sclerotic appearance with a thin superficial cellular zone resembling granulation tissue. Another morphological characteristic was a marked capillary proliferation revealed by immunohistochemical reactions to factor VIII-associated protein, laminin, and collagen IV. The last feature appears to be an integral part of the process, which most closely resembled fibromatosis of the adult type, a rare pattern of growth in inflammatory pseudotumor. PMID- 1463097 TI - Myofibromatosis-like hemangiopericytoma metastasizing as differentiated vascular smooth-muscle and myosarcoma. Myopericytes as a subset of "myofibroblasts". AB - A thyroid hemangiopericytoma that was resected in a 5-year-old boy recurred insidiously in the larynx 8 years later. Marked cicatricial mucosal inflammation prevented a definitive pathologic diagnosis of recurrence until a nodule grew to obstruct the airway 15 years after initial surgery. After excision of the nodule, a larger sarcomatous metastasis was discovered in the upper esophagus and resected, but the patient eventually succumbed to widespread disease at the age of 20 years. The original tumor contained atypical pericytes and bundles of hyalinizing smooth muscle abutting on "staghorn vessels," a pattern similar to infantile myofibromatosis. Desmin immunostaining was negative in the pericytes but positive in smooth-muscle cells dispersed singly as well as in bundles. Both elements reacted strongly for vimentin and the alpha-isoform of actin (alpha-SMA) found in normal smooth muscle and pericytes. A third cell type showing dendritic processes and immunoreactivity for all three antigens was interpreted as a myopericyte. Spindled cells in multiple subsequent mucosal biopsy specimens stained retrospectively also positive for these antigens. Large bundles of vascular smooth muscle surrounded by radiating myocytes characterized the occluding laryngeal nodule. In the esophageal metastasis, which showed no histologic features typical of hemangiopericytoma, numerous mitotically active, small, vimentin+, desmin+, alpha-SMA+ cells often maintained shortened processes and tended to form nodular aggregates about capillaries. Single rows of pericytes accreted to endothelial tubes. Ultrastructurally, some cells contained myofilaments and irregular dense material or showed rare cell junctions and variable investment by a basal lamina.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463098 TI - Recipient of the 1992 Fred W. Stewart Award: Karl Lennert, M.D. PMID- 1463099 TI - Advice, remarks, and observations to young head and neck surgeons. PMID- 1463100 TI - Hayes Martin Lecture. Bill of responsibility. PMID- 1463101 TI - Cytokine expression by head and neck squamous cell carcinomas. AB - Cytokines are known to play an important role in host defense by regulating the function, growth, and differentiation of the cells of the immune system. We hypothesize that, in the tumor microenvironment, tumor cells and resident tissue cells (e.g., fibroblasts) also produce cytokines that may regulate the local immune response to tumors. Initially, homogenates of eight head and neck squamous cell carcinomas (HNSCC) were assayed for the presence of interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), and granulocyte-macrophage colony stimulating factor (GM-CSF) to establish the presence of these cytokines in the tumors in vivo. We detected IL-1 in all tumor homogenates and IL-4, IL-6, and GM CSF in some homogenates. To assess the ability of HNSCC to produce these cytokines, supernatants of short-term primary cultures of HNSCC were assayed for the same cytokines. No IL-1 was detected, although baseline levels of IL-4, IL-6, and GM-CSF were present. However, the stimulation of primary tumor cultures with exogenous IL-1 induced or significantly enhanced production of IL-4 (p < 0.01), IL-6 (p < 0.001), and GM-CSF (p < 0.02). These results support our hypothesis that HNSCC secrete cytokines that may influence the response of local immune cells. Our data also suggest that IL-1 may have a central role in regulating the local immune response through the enhancement or induction of cytokine production by tumor and/or resident tissue cells. PMID- 1463102 TI - Localized carcinoma of the external ear is an unrecognized aggressive disease with a high propensity for local regional recurrence. AB - Management problems in patients with recurrent squamous cell carcinoma (SCC) of the external ear (pinna) have prompted a review of the management and treatment outcomes of patients who present with localized disease. Forty patients were seen over a 15-year period (1972 to 1991). Thirty-six were men, and 4 were women, with an age range from 43 to 93 years (average age: 71 years). Presenting TNM status was stage 0 in 2 patients, stage I in 15 patients, stage II in 13 patients, stage III in 2 patients, stage IV in 4 patients, and unknown stage in 4 patients. Thirty-six patients had clinically negative nodes at presentation (N0), and 4 had palpable nodes (N+). The primary treatment was local excision in 13 patients, Mohs' micrographic surgery in 16 patients, local excision plus external beam radiotherapy in 4 patients, and radical resection (parotidectomy/neck dissection/mastoidectomy) with or without radiotherapy in 5 patients. Two patients with stage IV disease died after diagnosis and prior to treatment, and two other patients with stage IV disease received palliative chemotherapy. Twenty patients developed recurrence from 2 months to 8 years. It included nine local recurrences, eight regional recurrences (parotid/neck/mastoid), and three distant metastases (lung or brain). After treatment of the recurrences in 20 patients, 8 are alive 15 months to 16 years later, 2 patients died of other diseases, and 10 patients died of SCC. The recurrences were managed by reoperation, radiotherapy, or chemotherapy. From the results of this study, we conclude that localized carcinoma of the external ear has a high propensity for local and regional failure and merits more aggressive treatment of the primary lesion and elective treatment of the regional lymph nodes and parotid gland in high-risk patients. PMID- 1463103 TI - Prognostic significance of cervical lymph node metastases in differentiated thyroid cancer. AB - During the last decade, several analyses of prognostic factors for differentiated thyroid cancer (DTC) have been reported. Although these studies have established a framework for rational treatment planning, they have not fully answered questions regarding the prognostic significance of cervical lymph node metastases. An analysis of patients treated for DTC at our institution over a 34 year period has shown several factors to be significant by log-rank analysis, including the presence of cervical lymph node metastases, age greater than or equal to 50 years, a primary cancer size of greater than 3.0 cm, and distant metastases. Further analysis has shown the node-negative and node-positive patient groups to be similar in regard to age, size of primary cancer, and the presence of distant metastases. This report compares our data with those of other studies that have investigated the association of cervical lymph node metastases and a poorer prognosis in patients with DTC. When considered as a group, these studies support the finding of the prognostic significance of cervical lymph node metastases, particularly that of palpable lymphadenopathy in older patients. PMID- 1463104 TI - Comprehensive treatment strategy for oral and oropharyngeal cancer. AB - This prospective nonrandomized study analyzes the effectiveness of the following treatment protocol for oral and oropharyngeal cancers: (1) radical initial surgery; (2) elective modified or selective neck dissection for NO necks; (3) jaw preservation unless gross invasion is present; (4) radial forearm freeflap reconstruction; (5) elective tracheotomy; (6) postoperative radiotherapy unless previously given; and (7) active oral rehabilitation. Between 1987 and 1992, 75 patients (55 men and 20 women) with a median age of 58 years had this treatment. Fifteen had been previously treated with radiotherapy. Clinical stages of untreated patients were as follows: 4 patients, stage I; 25 patients, stage II; 12 patients, stage III; and 19 patients, stage IV. Ten patients had segmental jaw resection, 26 had a marginal mandibulectomy, and 26 had a jaw swing. There were no operative deaths, and only one flap (1.2%) failed. Median times for oral feeds and hospital stay were 8 and 17 days, respectively. Forty-four patients had postoperative radiotherapy. Median follow-up time is 30 months, and locoregional control is 95% for previously untreated patients and 54% for previously treated patients. Thirteen patients have died of disease, 8 with locoregional recurrence and 5 with distant metastases alone. We conclude that this treatment strategy is highly effective in previously untreated patients but less effective in salvaging patients in whom radiotherapy has failed. PMID- 1463105 TI - Results of surgical treatment of T3 and T4 tumors of the oral cavity and oropharynx. AB - The combined use of surgery and radiotherapy is commonly accepted as the most effective treatment for locally advanced head and neck cancers. T3 and T4 tumors of the oral cavity and oropharynx often necessitate extensive local surgery. From 1981 to 1988, 199 patients with T3 and T4 tumors of the oral cavity and oropharynx were treated. One hundred seventeen patients underwent surgery plus postoperative radiotherapy; 78 had flap reconstructions. This series is extremely homogeneous because surgery was always performed by two surgeons, whereas radiotherapy was the responsibility of the same physician. The results of this study show a 96% local control rate at the end of treatment among the patients with combined treatment. The average time by which hospitalization was prolonged due to surgery was 29 days. The type and delay of recurrences and survival in relation with node involvement are also discussed. Extensive surgery in association with radiotherapy remains a reliable treatment in such patients. PMID- 1463106 TI - Results of surgical resection of pulmonary metastases of squamous cell carcinoma of the head and neck. AB - In this retrospective review of 58 patients (12 females and 46 males) with pulmonary metastases of squamous cell carcinoma of the head and neck treated between January 1, 1970, and December 31, 1989, we evaluated their clinical courses and analyzed the outcomes of those who underwent pulmonary resection. For the entire group of patients, factors predictive of survival in those patients with a diagnosis of pulmonary metastases included pulmonary resection of metastases (p = 0.0001), locoregional control of the head and neck primary tumor at the time of diagnosis of pulmonary metastases (p = 0.007), TNM stage of the head and neck primary tumor (p = 0.02), a single nodule seen on the chest radiograph (p = 0.02), and disease-free interval (DFI) from the primary tumor of the head and neck of 2 years or more (p = 0.05). Twenty-four of 58 patients underwent thoracotomy for resection of metastases. Four (17%) were found to have a second primary tumor of the lung. Of the 20 remaining patients who underwent explorative surgery for possible pulmonary resection, 18 (90%) underwent complete resection of all malignant disease with an estimated 5-year survival of 29%. In these patients, a DFI of less than 1 year was associated with a 5-year survival rate of 0%, whereas a DFI of 1 to 2 years was associated with a 5-year survival rate of 43% and a DFI of 2 years or longer had a 5-year survival rate of 33%. The number of malignant pulmonary nodules that were resected ranged from one to five and was not significant in predicting survival (p = 0.19). Of eight patients who underwent the resection of more than one malignant pulmonary nodule, 50% survived 2 years, but none survived 5 years. Resection of a solitary pulmonary metastasis from squamous cell carcinoma of the head and neck resulted in long-term survival in selected patients. Important prognostic factors included locoregional control of the head and neck primary tumor, the number of nodules seen on chest radiograph, the TNM stage of the primary tumor, and the DFI from the head and neck primary tumor. The value of resection in patients with more than one malignant pulmonary nodule remains to be defined for this group of patients. PMID- 1463107 TI - Patterns of failure after radical neck dissection for recurrent nasopharyngeal carcinoma. AB - Radical neck dissection (RND) for recurrent nasopharyngeal carcinoma (NPC) after radiotherapy was retrospectively evaluated in 38 patients treated between April 1986 and December 1991. Thirty patients (79%) had advanced-stage disease. Four patients required nasopharyngectomy as well as RND. The mortality was 0%, and the morbidity was 13%. The actuarial survival rates at 5 years from the time of initial radiotherapy and RND were 50% and 25%, respectively. Of the 21 patients with relapses after surgical salvage, 5 had recurrences in the nasopharynx, 3 had recurrences in the neck, and 13 had distant metastases. We conclude that RND for recurrent NPC is safe and efficacious; however, it is associated with a significant (34%) incidence of distant metastases. These results can be improved by evaluating patients for distant metastases and excluding those with distant metastases. Improvement in the treatment of distant metastases is also needed. PMID- 1463108 TI - Role of frozen section and clinical parameters in distinguishing benign from malignant follicular neoplasms of the thyroid. AB - The determination of malignancy preoperatively or intraoperatively is difficult in patients with follicular neoplasms of the thyroid. This study reviews a series of 395 patients treated for follicular neoplasms at the Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1955 and 1988, 198 of whom had frozen section at the time of surgery. Frozen section was 79% accurate in differentiating follicular adenomas from carcinomas, with a sensitivity of 52% and a specificity of 100%. The positive predictive value of a frozen section showing carcinoma was 100%, and the negative predictive value was 73%. An incorrect diagnosis of a benign lesion was made in 21% of patients in whom the final diagnosis by fixed section was carcinoma. These same statistics were calculated for patients aged greater than 50 years, tumor size greater than 3 cm, and patients with a history of previous neck irradiation, three clinical factors shown in a previous study to be strong prognostic indicators of malignancy. The results were compared with those found by frozen section. The implications of these results in terms of patient management are discussed. PMID- 1463109 TI - Parathyroid re-exploration. AB - The authors evaluated their experience with 27 patients who required parathyroid re-explorations. The initial exploration was unsuccessful in 20 patients: in 8 because of ectopic lesions, in 2 because of undetected supernumerary glands, and in 10 because of inadequate exploration of the neck. All of the patients with inadequate neck explorations were found to have eutopic disease. Seven patients required re-exploration because of recurrent disease. Localization studies were performed prior to re-explorative surgery in 26 of 27 patients, which resulted in successful placement in 21. Invasive procedures, selective vein catheterization, and/or arteriography were effective in 12 of 15 patients. Noninvasive procedures, including thallium-technetium scintigraphy, magnetic resonance imaging, computed tomography, and ultrasonography, were accurate in 14 of 21 patients. Twenty-three (85%) of 27 patients were cured, including 17 of 20 patients after an unsuccessful initial exploration and 6 of 7 patients with recurrent disease. Careful review of operative and pathology reports from the initial surgery was essential in determining the adequacy of the exploration, the presence of microscopic abnormalities, and the glands that were positively identified. Such analysis, in conjunction with noninvasive localization studies, will lead to successful re-exploration in the majority of cases. PMID- 1463110 TI - Phorbol dibutyrate plus ionomycin improves the generation of cytotoxic T cells from draining lymph nodes of patients with advanced head and neck cancer. AB - Fifty-one cervical nodes from 19 patients with advanced head and neck cancer were stimulated with phorbol dibutyrate and ionomycin (PDBu + Io) to determine the effect of such stimulation on the generation of cytotoxic T cells and whether this stimulation could bypass the need for autologous tumor stimulation. Lymphocytes stimulated with PDBu + Io demonstrated a sixfold greater in vitro expansion and significantly increased DNA synthesis. Whereas fresh lymphocytes displayed no cytotoxicity, stimulation with PDBu + Io and culture in interleukin 2 (IL-2) led to significant cytotoxicity equivalent to that of lymphocytes stimulated with autologous tumor and IL-2. T cells with the greatest cytotoxicity were generated from patients with nodal metastases. In patients with stage IV tumors, effector cells demonstrating greater lysis of natural killer-resistant targets (Daudi cells) were associated with higher rates of recurrence (50% versus 12%, respectively, p < 0.001). Stimulation with PDBu + Io augments growth and proliferation of lymphocytes from draining lymph nodes and preserves cytotoxicity without the need for autologous tumor. Excluding the need for antigenic stimulation by autologous tumor may prove useful in adoptive immunotherapy procedures. PMID- 1463111 TI - Comparison of the rectus abdominis free flap with the pectoralis major myocutaneous flap for reconstructions in the head and neck. AB - The pectoralis major myocutaneous flap (PMMF) is often used in the reconstruction of large head and neck defects. Unfortunately, its use is associated with a high incidence of minor complications, can distort the contour of the neck, and may cause significant donor site deformity, especially in women. This study compared 30 patients with major head and neck cancer-related defects who underwent reconstruction with a rectus abdominis free flap (RAFF) with 39 patients with similar defects who underwent reconstruction with the PMMF. The complication rate found in the RAFF group (13%) was significantly lower than that found in the PMMF group (44%; p = 0.0145). Flap necrosis was found in 10% of the PMMF group, whereas none was found in the RAFF group. The aesthetic outcome was also better in patients who had reconstructions with the RAFF. We conclude that, for most major head and neck defects, reconstruction methods that utilize the RAFF and other free tissue transfer techniques are preferable when the requisite equipment and expertise are available. PMID- 1463112 TI - Postlaryngectomy quality-of-life dimensions identified by patients and health care professionals. AB - We compared the quality-of-life (QOL) dimensions after laryngectomy in patients with advanced larynx or pharynx cancer that were elicited from 20 consecutive laryngectomy patients and 20 health care professionals working in the Regional Head and Neck Oncology Service. Subjects in both groups were asked to identify important QOL items after recovery from laryngectomy and to rank and rate each on a vertical visual analogue scale. Health care professionals ranked impaired communication and self-image/self-esteem as the two most important QOL dimensions, whereas patients ranked the physical consequences of surgery, e.g., tracheal mucous production, and interference with social activities as the two most important items. The results indicate that the responses of health care professionals do not fully correlate with patient priorities. These findings are relevant to researchers developing treatment-specific QOL measures and to health care professionals when presenting treatment options to patients. PMID- 1463113 TI - Optimizing primary treatment for advanced laryngeal and pyriform sinus carcinoma. AB - Advocates of chemotherapy plus radiation as the definitive treatment for patients with advanced laryngeal cancer often cite older studies that attribute cure rates of less than 50% to laryngectomy plus radiation. The outcomes of patients with stage III and IV laryngeal and pyriform sinus carcinoma from 1980 to 1989 (96 patients) were compared with those of patients treated from 1962 to 1977 (84 patients). Demographics, the extent of disease, and nodal involvement were similar between the groups. There were more operative complications (45% versus 22%; p < 0.01) and deaths (10% versus 2%; p < 0.01) in the patients who underwent irradiation preoperatively. Overall survival was improved in the recent group compared with the early group (73% versus 54% at 5 years; p < 0.03), as was disease-free survival (64% versus 38% at 5 years; p < 0.02). Results of treatment for advanced laryngeal and pyriform sinus carcinoma have improved significantly. These modern results should be used to evaluate newer treatment modalities. PMID- 1463114 TI - Identification of the external branch of the superior laryngeal nerve during thyroidectomy. AB - Seventy-six patients underwent preoperative vocal evaluation and were randomized into 3 groups: (1) those with the superior thyroid pole dissected by the first author, with the external branch of the superior laryngeal nerve (EBSLN) identified by means of a nerve stimulator; (2) those patients whose dissection was executed by a resident, with no nerve search; and (3) those whose dissection was undertaken by the first author, without any nerve search. Postoperative analysis consisted of voice evaluation and electromyography of the cricothyroid muscle. No lesion occurred in patients in group 1. Twenty-eight percent of patients in group 2 and 12% in group 3 experienced a complete lesion of the EBSLN (p = 0.0123). When the patients in group 1 were compared with the patients with 62 nerves corresponding to nonoperated thyroid lobes, patients in group 1 exhibited no increased risk, whereas a significantly increased hazard was evident in both groups 2 (p = 0.0002776) and 3 (p = 0.0346393). In this study, effective prevention of iatrogenic EBSLN lesions during thyroidectomies was achieved only by the intraoperative identification of the nerve with the nerve stimulator. PMID- 1463115 TI - DNA image cytometric analysis of differentiated thyroid adenocarcinoma specimens. AB - A total of 117 differentiated thyroid adenocarcinomas that had been removed by total thyroidectomy were studied. Seventy (60%) were papillary, 36 (30%) were follicular, and 11 (10%) were Hurthle cell adenocarcinomas. The mean length of follow-up was 57.7 months. Adverse prognostic factors according to multivariate analysis were adjacent tissue infiltration (p = 0.0004), histologic type (p = 0.0049), and patient age (p = 0.033). The nuclear DNA content of tumor cells and of morphologically normal adjacent tissue was assessed by image cytometry, and correlations between nuclear DNA content and prognostic factors were examined. Fifty-four (75%) adenocarcinomas were classified as aneuploid, 9 (13%) as diploid, and 9 (12%) as borderline. Thirty-four (60%) specimens of morphologically normal adjacent tissue were classified as aneuploid, 18 (32%) as diploid, and 5 (8%) as borderline. The correlation between tumor ploidy and selected prognostic factors was statistically significant for patient age (p = 0.004) and histologic type (p = 0.033). Despite the fact that ploidy could not be identified as a prognostic factor, we suggest that, because of its correlation with age and histologic type, it might prove prognostic if the number of patients were increased. We also emphasize the importance of evaluating morphologically normal adjacent tissue because of the high rates of aneuploidy in these areas. PMID- 1463116 TI - Temporal bone resections for carcinoma of the middle ear and the external ear canal. AB - Petrosectomy has been used in the management of carcinoma of the external ear canal and the middle ear for the last 45 years. In recent years, there have been conflicting reports; some authors advocate a conservative approach, whereas others support an ultraradical approach. Most retrospective studies report patients who have been treated with radiotherapy or surgery as having undergone the primary modality depending on where the patient first presented. No selection criteria seem to have been employed. Although radiotherapy was used postoperatively, the problems of wound healing were not addressed. This study presents our experience with temporal bone resection as described by Lewis and shows that, in combination with patient selection and proper choice of incision, reconstruction and timely postoperative radiotherapy can achieve better results, and the patient's quality of life can be preserved. PMID- 1463117 TI - p53 overexpression correlates with increased survival in patients with squamous carcinoma of the tongue base. AB - Epidermal growth factor receptor (EGFR), transforming growth factor alpha (TGFA), and p53 are frequently overexpressed in squamous cell carcinomas (SCC) of the upper aerodigestive tract. We chose to study SCC of the tongue base, which is often advanced at presentation and fatal, to evaluate whether overexpression correlates with survival. Complete follow-up was available for 20 patients, 18 of whom had stage III or IV disease. A number of clinical (age, sex, stage of disease) and histologic (tumor grade, keratinization, mitotic rate, perineural invasion, lymphatic invasion, vascular invasion, host response) variables were analyzed. None of these variables correlated with survival. Immunohistochemical analysis was performed on paraffin-embedded tissue from each patient. Because EGFR and TGFA expression were routinely found in normal squamous epithelium, overexpression was considered present if greater uptake of the antibody was manifested by a deeper immunostain. In contrast, p53 oncoprotein was not detected in normal epithelium, so detection of the antibody was believed to indicate overexpression. EGFR was overexpressed in 60% of tumors, TGFA in 35%, and p53 in 20%. Those patients who had an overexpression of p53 had a greater mean survival than those who did not (48 versus 16 months, respectively, p = 0.06). This difference was significant for patients with clinical stage IV lesions (p = 0.03). EGFR overexpression and TGFA overexpression did not correlate with survival. p53 may serve as a biologic marker indicative of improved survival potential. PMID- 1463118 TI - Role of ultrasound in the management of thyroid nodules. AB - One hundred twenty patients undergoing thyroid surgery for thyroid nodules or goiter were examined by preoperative ultrasound and fine needle aspiration (FNA) cytology. In the determination of whether a lesion was malignant, FNA had sensitivity, specificity, and positive predictive values of 86%, 85%, and 58%, respectively. Ultrasound had sensitivity, specificity, and positive predictive values of 74%, 83%, and 51%, respectively. The different types of thyroid pathology showed different ultrasonic features in most cases, although no single feature was pathognomonic. Malignant lesions tended to be solid and hypoechoic without a halo, but there was a cystic element in 26% of the lesions and calcification in 37%. Ultrasound was superior to FNA in diagnosing nodular goiter with sensitivity, specificity, and positive predictive values of 70%, 93%, and 92%, respectively, compared with 55%, 86%, and 83%, respectively. The two modalities are complementary. PMID- 1463119 TI - Prognostic factors in differentiated carcinoma of the thyroid gland. AB - A retrospective review of a consecutive series of 931 previously untreated patients with differentiated thyroid carcinoma treated over a 50-year period was undertaken to analyze prognostic factors. Data pertaining to demographic status, clinical, operative, and pathologic findings, and survival were analyzed. Univariate statistical analysis was performed based on the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed to assess the independent effect of these variables using the Cox model. There were 630 female and 301 male patients, with an average age of 43 years. A total of 532 patients were younger than 45 years. Seven hundred thirty-one patients had either pure or mixed papillary carcinoma, and 200 had follicular carcinoma. In 153 patients, lesions were larger than 4 cm. Extrathyroidal extension was noted in 71 patients. Multifocal lesions were present in 159 patients. Regional lymph node metastasis was present on admission in 451 patients, and distant metastases were noted on presentation in 45 patients. Determinate survival for all patients was 87% at 10 years. Favorable prognostic factors using univariate analysis included female gender, multifocal primary tumors, and regional lymph node metastases. Adverse prognostic factors included age over 45 years, follicular histology, extrathyroidal extension, tumor size exceeding 4 cm, and the presence of distant metastases. On multivariate analysis, the only factors that affected the prognosis were patient age, histology, tumor size, extrathyroidal extension, and distant metastases. These observations support findings of reports from the Mayo Clinic and Lahey Clinic regarding the significance of prognostic factors for differentiated carcinoma of the thyroid gland. PMID- 1463120 TI - Healing of microvascular free skin flaps in irradiated recipient tissue beds. AB - This laboratory study compared the biomechanical and biochemical healing of microvascular free skin flaps in irradiated and nonirradiated recipient areas. In the adult rat, the skin of the right groin region was exposed to a single fraction dose of 20 Gy, using a linear megavoltage accelerator. The left groin was shielded. One week after radiotherapy, the left femoral artery and vein were divided, and an anastomosis was created in situ at the site of the epigastric pedicle. The epigastric skin flap was crossed over to replace the central area of the irradiated skin in the contralateral right groin. The healing of the interface between the irradiated recipient skin and the transferred free epigastric flap was studied at 4 weeks. A comparison was made with the microvascular free flaps of nonirradiated control animals. An additional group of control animals was used to verify the retarding effect of the 20-Gy radiation dose on wound healing. In control animals, the single dose of 20 Gy decreased the tensile strength of standardized surgical wounds by 23% (p = 0.03). Clinical healing of the transferred microvascular free flaps between the irradiated and control recipient areas was comparable, and the flaps showed no significant differences in the mechanical incorporation. The biochemical assays of the DNA, RNA-ribose, total nitrogen, and hydroxyproline contents of the flap showed an increased concentration of proteins (total nitrogen) expressed per cell count (DNA) (25%, p = 0.04), reflecting the excessive accumulation of organic matrix and a relatively decreased number of cells in irradiated recipient tissues. We conclude that there are no major differences in the healing capacity of microvascular free skin flaps between irradiated and nonirradiated recipient areas. PMID- 1463121 TI - Value of fine needle aspiration biopsy of salivary gland masses in clinical decision-making. AB - The accuracy of fine needle aspiration biopsy (FNAB) in the diagnosis of salivary tumors has been well established. This study was undertaken to determine the impact of FNAB on patient management. One hundred one patients underwent FNAB of major salivary gland masses. The physician's initial clinical impression was compared with the FNAB diagnosis and the final diagnosis in each case. Forty patients had solitary masses thought to be benign tumors other than Warthin's tumors. FNAB in 13 of these patients (33%) yielded a diagnosis permitting modification of the planned procedure. The diagnosis of Warthin's tumor was suspected clinically in 23 patients. In nine of these patients (39%), FNAB resulted in a different diagnosis. Of the 10 patients believed to have malignant tumors, using FNAB, 1 was found to have sialadenitis and 1 a lymphoma. Overall, FNAB resulted in a change in the clinical approach to 35% of the patients. We recommend the performance of FNAB in almost all patients with salivary masses. PMID- 1463123 TI - Osseointegrated implants and functional prosthetic rehabilitation in microvascular fibula free flap reconstructed mandibles. AB - The mandibulectomy deformity can be alleviated by immediate mandibular reconstruction using the microvascular fibula free flap. Before the advent of microvascular reconstruction, conventional and maxillofacial prosthetic rehabilitation offered limited success after surgery due to the failure to reestablish the bony foundation and soft tissues (tongue, floor of mouth, vestibule) anatomically and physiologically. With proper multidisciplinary pretreatment planning and postoperative treatment, osseointegrated implants can be strategically placed in patients with these reconstructed mandibles to restore occlusal and masticatory function. The records of seven patients who underwent reconstructive surgery and osseointegrated implants were reviewed, with an emphasis on the variety of prosthetic designs and principles used to maximize long-term efficiency and preservation of tissues. PMID- 1463122 TI - Prognostic factors and management considerations in patients with cervical metastases of thyroid cancer. AB - Included among the controversies involving thyroid cancer are the risk factors and treatment decisions in patients with nodal metastases. We have reviewed selected clinical, pathologic, and therapeutic parameters in patients who present with cervical node metastases and related these parameters to disease outcome. There were 108 patients (68 women, 40 men), who had a mean age of 54 years. Univariate analysis showed a significantly increased risk of recurrence to be associated with the presence of primary tumor invasion (vascular, lymphatic, nerve, or muscle), the age and sex of the patient, the presence of mediastinal nodes, and adjuvant treatment with iodine 131. The presence of tumor invasion, the age and sex of the patient, and the presence of mediastinal nodes were significantly associated with higher rates of recurrence when tested by multivariate analysis. The 5- and 10-year disease-free survival rates were 76% and 72%, respectively, with a mean follow-up of 86 months. A comparison of recurrence and survival rates in thyroid cancer patients who were either node positive or node negative during the same 10-year period (152 patients) showed no statistically significant differences. However, node-positive patients with the risk factors of tumor invasion, age over 45 years, and positive mediastinal nodes had more aggressive disease. Although thyroid cancer patients with nodal metastases generally have a good prognosis, high-risk subgroups have been identified who may benefit from a more aggressive therapeutic and follow-up approach. PMID- 1463125 TI - The Alaska Trauma Registry. AB - Recognizing that injury is the leading cause of death and disability for virtually all age groups in Alaska, a trauma task force was developed in the Anchorage area in the early 1980s. This task force established the trauma registry pilot project in the state of Alaska. The Emergency medical Services Section, Department of Health and Social Services provided the funding to the Southern Region Emergency Medical Services Council, Inc. and the Alaska Chapter of the American College of Surgeons Committee on Trauma to develop this pilot project. The funding originated from a federal grant from the National Highway Traffic Safety Administration. Seven hospital participated in the pilot project which lasted approximately two and one half years. There were 5,087 entries into the registry with information on 4,860 patients. The rationale, methodology, and development of the registry, as well as some of the data accumulated is presented. The potential usefulness of the registry as a quality improvement tool and as an extensive data base for injury prevention and trauma care research also is discussed. PMID- 1463124 TI - Prognostic factors for survival in patients with T3 laryngeal carcinoma. AB - In a total of 511 patients with T3,N0-3,M0 laryngeal carcinoma, 24 possible prognostic factors were analyzed retrospectively. The factors were age, sex, mode of treatment, duration of several clinical symptoms, the presence of sore throat, otalgia, dyspnea, and dysphagia, previous tracheotomy, tumor extension, lymph node status (five items), histologic grading, smoking habits, and alcohol intake. For 300 patients in whom surgery was part of the primary treatment, pathologic staging of the primary tumor and of lymph nodes in neck dissection specimens, cartilage invasion, radicality of the operation, differentiation grade, and subglottic extension ware also evaluated. In a univariate analysis for the whole group, tumor extension (limited to the glottic region), lymph node status (clinically palpable lymph nodes, cytologically confirmed positive lymph nodes), level of lymph node metastasis (high and midjugular site), histologic grading (poor differentiation grade), and treatment modality (planned combined therapy) were considered to be prognostic factors of corrected actuarial survival. In the group that underwent surgery, all factors derived from specimens of the larynx and neck dissections had prognostic significance. Multivariate analysis revealed that the glottic site of the tumor, the presence of cyto- and histopathologically proven metastatic lymph nodes, pretreatment tracheotomy, positive resection margins, and planned combined treatment had a significant influence on corrected actuarial survival. PMID- 1463126 TI - Health Locus of Control in Chukotka children. AB - Two groups of children in the cities of Anadyr and Pevek in the Chukotka Region of the Soviet Far East were administered a Russian translation of the Children's Health Locus of Control Scale in July, 1991. Results were analyzed to assess the similarities between response patterns among the Russian children and those found in American children. The analyses revealed a consistency in the data suggesting both face and theoretical validity of the Scale. It appears that the underlying mediating variable related to the children's perceived control over their health is operating in this Region of Russia in much the same way that it does in the United States. PMID- 1463127 TI - Peripherally inserted central catheters--review and case reports. AB - Patients have been receiving intravenous therapies in their homes since the early 1980s. Peripherally inserted central catheters have recently played a major part in the successful transition from hospital to home. These catheters are less invasive, have a lower overall infection rate and are less costly than other central venous catheters. This review and presentation of two case studies illustrates the advantages of this type of catheter for patients receiving home intravenous therapy. PMID- 1463129 TI - Explaining Alaska's Certificate of Need program. PMID- 1463128 TI - Health care in the workplace. PMID- 1463130 TI - A weekend with Joseph Lopiccolo, M.D. AB - There were many interesting issues discussed at the workshop and I will explore them more in-depth in later issues. For now, enjoy the transitions of the season and I'll be returning back to infertility in the next issue. PMID- 1463131 TI - Prescription medications--some important guidelines. PMID- 1463132 TI - Where is the drug problem? AB - This article traces the history of drug use from its earliest use to the present time. It treats alcohol and the "other drugs," but deals more with alcohol since this has been the major drug of use. It outlines the many problems associated with use and abuse, the legislation passed as an effort to control these and finally, the effect of the Uniform Alcoholism Act of 1970. This was followed by changing public attitudes toward alcohol and the development of many effective treatment programs, while the "other drug" problem remains unresolved in spite of a similar attempt through the Uniform Controlled Substances Act of 1970. PMID- 1463133 TI - Janice Kastella, M.D. PMID- 1463134 TI - Vaccination, the Tlingit, and a missionary's faith (1835-36). PMID- 1463135 TI - [Frontiers in surgery: nerve cell transplants]. PMID- 1463136 TI - [Reflections on juvenile obesity]. PMID- 1463137 TI - [Flow cytometry in pathological anatomy]. PMID- 1463138 TI - [Drug surveillance: the concept, the need and methods]. PMID- 1463139 TI - [An infrequent form of lithiasis (renal milk of calcium or renal oolitic gravel)]. PMID- 1463140 TI - [Electromagnetic radiation and health]. PMID- 1463141 TI - [Obesity: a physiopathological update]. PMID- 1463142 TI - [Epidemiology of rabies as a current problem]. PMID- 1463143 TI - [Current trends in the medical treatment of solid tumors]. PMID- 1463144 TI - [Epidemiological aspects of viral hepatitis: immunogenicity of hepatitis B vaccine administered to children and adolescents]. PMID- 1463146 TI - [Requiem for general pathology?]. PMID- 1463145 TI - [Hepatitis B in health personnel: vaccination campaign]. PMID- 1463147 TI - [Gabriel Miro in front of death: from rebellion to resignation]. PMID- 1463148 TI - [Rapid destructive arthropathy]. PMID- 1463149 TI - [Methods of analysis of ethical problems in human clinical practice]. PMID- 1463150 TI - [Oscillation and resonance in the central nervous system]. PMID- 1463151 TI - [In memoriam of Antonio Gallego Fernandez]. PMID- 1463152 TI - [Terrorism of energetics (the threat of electromagnetic fields)]. PMID- 1463153 TI - [New aspects of funicular pathology]. PMID- 1463154 TI - [Premedication in retrobulbar anesthesia. A blood gas analysis comparison of sublingual flunitrazepam and intravenous midazolam]. AB - Benzodiazepines for sedation may decrease the PaO2, the arterial O2 saturation (SaO2), and the CO2 response more in the elderly than in the young. The purpose of this study was to assess changes in blood gases due to i.v. midazolam or sublingual flunitrazepam given as premedication in elderly patients for unilateral cataract surgery. METHODS. Fifty patients over 65 years of age with treated arterial hypertension and other co-existing diseases (ASA III-IV) were randomly assigned to have: (1) i.v. midazolam titrated until they became drowsy (17 patients; 2.85 +/- 0.84 mg [mean +/- SD]); (2) sublingual flunitrazepam (16 patients; 0.005 mg/kg); or (3) no sedation (17 patients; controls). On entering the operating theatre, the radial artery was cannulated and the first blood gas analysis was obtained. The premedication was then given. At 5, 10, 20, and 30 min after premedication, before and 10 min after retrobulbar block, before operation, 5 and 15 min after the beginning of the operation, 10 and 20 min after administration of 500 mg acetazolamide i.v. during the operation, and 10 and 20 min after the operation additional arterial blood samples were analysed (a total of 15 measuring points). Pulse oximetry, invasive blood pressure, and ECG were continuously monitored. All patients received oxygen 3 l/min during the operation by nasal cannula. Differences between the three groups were analysed by Student's t-test or U-test and a P value < 0.05 was considered significant. RESULTS. The patient demography, including duration of anaesthesia and operation, was similar in the three groups (Table 1). No significant differences were seen in heart rate, mean arterial pressure, PaO2, pulse-oximetric oxygen saturation (SpO2), base excess, or serum bicarbonate levels. The PaCO2 increased in patients after midazolam (P < 0.01) and flunitrazepam (P < 0.05) until the beginning of the operation compared with the control group (Fig. 3); 20 min after the operation there was still a significant difference between the midazolam group and the controls. SaO2 was significantly (P < 0.05) lower in the midazolam group 10 and 20 min after administration of premedication compared with the control group, but was within physiological limits (Fig. 5). Despite titration, 2 patients had severe respiratory insufficiency 3 min after midazolam: the SpO2 decreased below 85% and the paO2 below 55 mmHg. The paCO2 was higher (P < 0.05) in the midazolam group 10 min after acetazolamide compared with the controls. CONCLUSIONS. The results of the study show the potential hazards of i.v. midazolam in the elderly. If sedation is required for cataract surgery under local anaesthesia, we recommend sublingual flunitrazepam or the use of benzodiazepines with lower hypnogenic effects in the elderly. A thorough preoperative discussion of anaesthesia and the operation might be an adequate substitute for any premedication in high-risk patients; the best blood gas analysis results were obtained in the control group. PMID- 1463155 TI - [Suppression of the adrenal cortex by enoximone. A proband study with documentation of the hemodynamic course]. AB - In contrast to the bipyridine derivatives amrinone and milrinone, the phosphodiesterase III/IV inhibitor enoximone is an imidazolone that creates the possibility of inhibiting adrenal steroid synthesis, as has already been demonstrated for other imidazoles, e.g. ketoconazole and etomidate. To clarify this point we carried out a double-blind sequential study in seven healthy volunteers. METHODS. After obtaining the approval of the ethics committee and the written consent of the volunteers, 1.25 mg/kg enoximone or saline was infused intravenously over a period of 20 min using a randomized crossover design with an interval of at least 5 days between the two trials. Twenty minutes after administration of the drug, 250 micrograms ACTH was injected. Plasma cortisol was measured prior to stimulation of the adrenal cortex and 30, 60 and 120 min afterwards; levels of aldosterone and 11-desoxy-cortisol were determined after 60 min. Standard radioimmunoassays were used. Haemodynamic parameters were measured non-invasively. RESULTS. In contrast to the placebo, enoximone resulted in a significant (P < 0.01) increase in the cardiac index (from 3.2 +/- 0.7 to 3.9 +/- 0.9 l min-1 m-2) and heart rate (from 69 +/- 11 to 81 +/- 8 min-1) and a decrease in peripheral resistance (from 1120 +/- 202 to 894 +/- 183 dyn s cm-5); blood pressure fell only slightly. Following injection of ACTH there were significant increases in cortisol (from 63 +/- 29 to 274 +/- 58 micrograms/l), aldosterone (from 86 +/- 37 to 300 +/- 105 ng/l) (both P < 0.001) and 11-desoxycortisol (from 5.3 +/- 1.2 to 9.8 +/- 4.6 micrograms/l; P < 0.05). There was no difference between enoximone and placebo at any time (P > 0.2). CONCLUSIONS. This study confirms the inodilation caused by enoximone. The normal response to ACTH rules out a direct inhibitory effect of a loading dose of 1.25 mg enoximone on the adrenal cortex. As the concentration of the major metabolite of enoximone, the sulphoxide, has been shown to surmount that of the parent drug after 40 min, this also holds true for the metabolite. We conclude that in contrast to etomidate, which causes a substantial reversible adrenal suppression after a single dose of 0.2 mg/kg, enoximone 1.25 mg/kg did not interfere with corticosteroid synthesis or release. Taking into account the metabolism and pharmacokinetics of this inodilator, there is no reason to expect an inhibitory effect even after repeated dosage. PMID- 1463156 TI - [Subdural intra-arachnoid spread of local anesthetics. A complication of spinal anesthesia]. AB - Accidental subdural injections and catheterisations are a complication of epidural and spinal anaesthesia. The incidence of subdural spread in myelographies is estimated to be over 10% by the spinal technique. With spinaloscopy in an anatomic human model, we analysed the puncture process and the influence of different needle types on the incidence of subdural injection. We compared 22-gauge Sprotte, Quincke, and 18-gauge Tuohy needles in median and paramedian approaches with various bevel orientations. METHOD. The studies were performed in a preserved and recently expired cadaver donated to the Institut fur Anatomie, Westfalische Wilhelms-Universitat, Munster. The spinal column from T12 to S1, together with the back musculature (in order to preserve the normal curvature of the spine), were removed from the cadaver. Spinaloscopy was performed with a 4-mm endoscope with a 0 degree optic (Storz, Tuttlingen, Germany). All observations were made in the lumbosacral region of the dissected preparation. The endoscope was inserted from the caudal end of the spinal canal and, depending on the observations being made, the spinal canal was filled with air or artificial cerebrospinal fluid (CSF). To obtain information on the distribution of local anaesthetics injected into the subarachnoid space, 0.5% bupivacaine was coloured with a small amount of 1% methylene blue. The distribution of the coloured anaesthetic was clearly visible during and after injection. RESULTS. Needle insertion: Multiple observations were made using median or paramedian advancement of the needle into the spinal canal. With all needles, including the pencil-point, we saw an unexpected inward movement of the dura to the epidural space before penetration. This dural movement was independent of the direction of the dural fibres in the lumbar area. Distribution of local anaesthetics: Our observations indicate that difficulty with injecting drugs occurred when needle insertion was stopped too close to the dura, especially with the Sprotte needle. After manually registered penetration of the dura, the lateral opening of the needle only partially penetrates the dura. This allows CSF to appear in the needle hub, and injection into the vertical subdural space is possible. In all cases with the Sprotte needle, we could reproduce deposition of methylene-blue-coloured local anaesthetics into the subdural space. With the Quincke and Thuohy needles, it was not possible to deposit local anaesthetics into the subdural space in this model. CONCLUSION. Spinaloscopy was done in a non-fixated anatomic preparation of a spinal column with a 4-mm, 0 degree endoscope. From these observations we conclude that both manually registered penetration of the dural and the appearance of CSF in the needle hub can mimic correct needle position. Especially with the lateral opening of the Sprotte needle, deposition of local anaesthetics in the subdural space is possible. PMID- 1463157 TI - [Intrathecal morphine for postoperative pain]. AB - At the beginning, the way intrathecal morphine was used for postoperative pain relief was quite unfortunate, because the doses derived from experience with morphine-tolerant cancer patients were considerably too high and respiratory depression occurred frequently. Subsequent dose-finding studies showed that the doses of morphine used initially could be reduced by a factor of ten without loss of the analgesic effect and with a marked reduction in side-effects. No respiratory depression has been reported when doses below 0.1 mg morphine are used. METHOD. In this prospective study the effect of 0.06 to 0.08 mg intrathecal morphine, mixed with the local anaesthetic for spinal anesthesia, was investigated in surgical patients aged 21 to 81 years, ASA grade I or II, scheduled for orthopaedic operations or herniorraphies. Thirty unpremedicated patients were enrolled in the study and were, after informed consent, randomly allocated to a control group without morphine or to a morphine group. The analgesic effect was assessed by the time interval between the administration of the spinal anaesthesia and the first demand for an analgesic medication. The mood state was evaluated with the adjective checklist of Janke and Debus 6 h after the spinal anaesthesia. RESULTS AND DISCUSSION. In the control group half of the patients asked for an analgesic medication within 275 min (median) after the spinal anaesthesia, and all patients within 420 min, whereas in the morphine group half of the patients asked for an analgesic within 1170 min (median). Seven patients had not required an analgesic at the termination of the observation period 20 h after the spinal anaesthesia. The mood status showed no difference between the two groups, in particular, no dizziness or drowsiness after morphine. There was no difference in the incidence of side-effects such as nausea or urinary retention between the two groups. Pruritus was not reported spontaneously but was found upon questioning in five patients. It was in no case disturbing. CONCLUSIONS. Morphine (0.06 to 0.08 mg) mixed with the local anaesthetic for spinal anaesthesia provided for an analgesia of more than 20 h duration in half of the patients. This technique is safe, simple, reliable and virtually free of side-effects. No particular supervision due to the administration of intrathecal morphine is necessary in this dose range if systemic opiates are avoided. If the analgesia is unsatisfactory, a non-opioid analgesic is recommended. PMID- 1463158 TI - [Registration and analysis of airway pressure and gas flow in ventilated patients. The "Hyper-DAQ Respiration Mechanics Recorder"]. AB - Respiratory data monitored in ventilated patients commonly consists of monitoring some inspiratory and expiratory pressures and volumes. For a more sophisticated analysis of respiratory mechanics in ventilated patients, a combined hardware and software system is presented that allows for continuous monitoring of airway pressure and gas flow. Gas flow is measured using a pneumotach. The "Hyper-DAQ" is an 8-channel 12-bit analog to a digital converter that can be connected to IBM PCs as well as to Macintosh computers using a standard RS 232 link. A special module consisting of three pressure transducers (airway pressure, differential pressure for a Fleisch head and ambient pressure) and five additional analog inputs is used for recording respiratory data. Once set up, the Hyper-DAQ records all the data in real time, independently of the host system that can query the data via the RS 232 link. The software runs on IBM and compatible PCs, as well as on Macintosh computers. The software simulates a strip-chart recorder and can be controlled by the keyboard and the mouse. We developed special software for the calibration of pressure and flow. Using models of the gas distribution in the lung compliance, resistance and lung time constants can be calculated from the raw data. For special purposes the data can be transferred to spread-sheet software. A mainstream CO2-detector connected to one of the additional analog inputs allows for additional data: alveolar ventilation, series deadspace, etc. The system presented can be recommended in routine work as well as for scientific studies in ventilated patients. PMID- 1463159 TI - [Vigilance disorders in intensive care patients. The central anticholinergic syndrome as a differential diagnosis of a brain stem lesion]. AB - Four days after implantation of a biventricular assist device (Berlin heart) the 39-year-old patient showed a sudden loss of vigilance and tetraplegia. Clinical skills and neurophysiological states indicated a serious lesion of the brain stem. After a test application of Physostigmine 2 days later, the neurological deficits improved dramatically. The case demonstrates that neurological deficits can also be caused by or combined with an acute anticholinergic syndrome. The application of Physostigmine allows disorders caused by brain lesions to be differentiated from transitory syndromes. PMID- 1463160 TI - [Acute jugular engorgement in liver transplantation]. AB - A 56-year-old patient with chronic liver failure underwent liver transplantation; a Denver shunt had been placed 6 months previously. Following an initially uneventful operative course, during fashioning of the proximal caval anastomosis in the anhepatic phase, the patient developed very marked jugular engorgement. The central venous pressure rose to 45 mmHg and this lasted some 15 min. With the opening of the venous anastomosis and placement of the liver in its anatomical site, the central venous pressure returned to normal values once again. It can be concluded that during fashioning of the anastomosis, both the right atrium and distal superior vena cava were obstructed. While normally not haemodynamically significant, in this case, however, the superior vena cava became more narrow by the routinely placed venous lines and the Denver shunt. This in turn, gave rise to this particular clinical manifestation. PMID- 1463161 TI - [Paravasal infusion over the proximal lumen of a Swan-Ganz catheter]. AB - In a severe traumatized patient (34 years old, 182 cm tall, 90 kg body wt.), we inserted a Swan-Ganz catheter (110 cm, 5 lumina, Modell 93A-831-7.5F, Baxter Healthcare) via the right internal jugular vein. Infusion was started using the proximal lumen. Several hours later we observed a large swelling on the right side of the neck and the supraclavicular region due to paravasal fluid administration while recording normal pulmonary artery and wedge pressure curves. The reasons and consequences are discussed. PMID- 1463162 TI - [Comments on the paper by N. Bang-Vojdanovski. Intrathecal opiate-spinal anesthesia. Clinical results of a 1-year study using 0.0375-0.15 mg morphine]. PMID- 1463163 TI - [Anesthesia in neuromuscular diseases]. PMID- 1463164 TI - Magill's endobronchial tubes. PMID- 1463165 TI - A Letter from the Editor. PMID- 1463166 TI - Complications of continuous spinal anaesthesia. AB - The practice of continuous spinal anaesthesia dates back to the beginning of the century. The history of the technique, and the problems which accompanied each method used, are reviewed. Complications encountered in current practice include post dural puncture headache; technical difficulties with insertion and removal of catheters; and a higher potential for nerve trauma, neurotoxicity, and method failure than seen with single-shot spinal anaesthesia. The question of the place of the technique in modern anaesthesia is addressed. PMID- 1463167 TI - Anaesthesia and breast-feeding--the effect on mother and infant. AB - In this paper, we summarise the physiology of lactation and discuss the pathophysiology brought about by fasting, stress and anaesthetic drugs. Drug secretion into breast milk and subsequent absorption by the infant is considered. Maternal hydration must be well maintained with intravenous fluids, allowing an added 500 to 1000 ml for daily fluid loss in lactation. Maternal premedication, general anaesthesia and routine postoperative analgesics are also discussed as to the effects on the breast-fed infant. Drug side-effects may be avoided by timing breast feeding just before the next due dose. Sedatives with long half-lives should not be used. Endocrine and metabolic responses to anaesthesia and surgery are less with regional anaesthesia than with general, hence regional anaesthesia is preferred where it is a reasonable alternative technique. PMID- 1463168 TI - Vasopressor therapy in cardiac resuscitation. AB - The standard 0.5 to 1.0 mg dose of adrenaline used in cardiac resuscitation may be inadequate on the basis of theoretical and experimental evidence. Well designed clinical trials are indicated to test the hypothesis that higher doses of adrenaline could be more effective in specific subgroups of people experiencing cardiac arrest. The success in resuscitation is related to the aortic diastolic pressure and the effectiveness of adrenaline relates to its peripheral vasopressor effect. Other catecholamines such as noradrenaline may be more efficacious, as could be non-adrenergic vasopressors. Clinical studies are required, however, to evaluate these potential alternatives. PMID- 1463169 TI - Mortality prediction in infants with congenital diaphragmatic hernia: potential criteria for ECMO. AB - Over the last ten years the survival of infants born with congenital diaphragmatic hernia who reach the Intensive Care Unit of the Royal Children's Hospital, Melbourne has been constant at 56 +/- 6%. Experimental therapies such as extracorporeal membrane oxygenation, high-frequency oscillation and lung transplantation are now being considered as therapeutic options, and as such the ability to predict survival or death of these infants is increasingly important. The records of all infants with congenital diaphragmatic hernia admitted to the Intensive Care Unit between 1 January 1980 and 30 April 1989 were reviewed; blood gas, ventilatory details, and outcome information was obtained. Receiver operating curve analysis was used to determine the best predictor of death. An oxygenation index (MAP x FiO2/PaO2) > 0.3 or ventilation index (PIP x RR x CO2/1000) > 70 predicted a 94% mortality with a specificity of 96% and a sensitivity of 82%. PMID- 1463170 TI - High-volume spinal anaesthesia. A dose-response study of bupivacaine 0.125%. AB - The clinical effects of high-volume spinal anaesthesia with bupivacaine 0.125% were studied in 30 patients presenting for postpartum sterilisation. Group A, B and C patients received 6, 8 and 10 ml of bupivacaine 0.125% respectively. Onset, duration and regression of sensory block and motor blockade, haemodynamic parameters and postoperative complications were studied. A sensory level of T10 was reliably obtained in Group B and C but not in Group A. Similarly motor blockade was unreliable in Group A compared with Group B (P < 0.05) and Group C (P < 0.05). Two segment regression times were similar in all three groups. L1 regression times were 47.9, 94.3 and 99.0 minutes in Groups A, B and C respectively. The corresponding times for complete recovery of motor power were 120, 212.3 and 182.7 minutes respectively (P < 0.01 when Group A compared to B and C). A significant incidence of high spinal anaesthesia occurred when 10 ml bupivacaine 0.125% was administered (P < 0.05 when compared with Group A). No patient experienced respiratory discomfort in spite of sensory levels of up to T1. Hypotension responded readily to intravenous fluids and small doses of ephedrine (three patients). Only one patient (Group A) developed a postdural puncture headache. In this study, high-volume spinal anaesthesia with bupivacaine 0.125% was found to be satisfactory for postpartum tubal ligation. The optimal volume of bupivacaine 0.125% was 8 ml. PMID- 1463171 TI - Use of warm local anaesthetic solution for caudal blocks. AB - A double-blind study was undertaken to investigate the effect of prewarmed local anaesthetic solution on the latency of onset of caudal blocks. Forty-four (ASA I II) patients were allocated into two equal groups. In Group A, the local anaesthetic solutions were injected at room temperature (25 degrees C), while in Group B, they were injected at 37 degrees C. All the caudal blocks were performed using 20 ml of lignocaine 1.5% with adrenaline 1:200,000. The speed of onset of perianal analgesia was found to be significantly faster (39%) with the prewarmed local anaesthetic solution (P < 0.05). No adverse effects were observed. PMID- 1463172 TI - Oxygen dissociation curve in the adult respiratory distress syndrome. AB - The oxygen tension for half saturation (P50) was determined for venous blood in thirteen patients with the adult respiratory distress syndrome undergoing intensive therapy. The mean value for P50 was found to be significantly lower than the value found in ten normal control subjects (22.9 mmHg and 26.7 mmHg respectively; t = 3.03, P < 0.01). The extent of reduction in P50 was not related to serum phosphate level nor was it a predictor of short-term outcome. It is unlikely that the slight left-shifted oxygen-haemoglobin dissociation curve contributes in a major way to an oxygen delivery deficiency and its cause is unexplained. PMID- 1463173 TI - Derived oxygen saturations are not clinically useful for the calculation of oxygen consumption. AB - In critically ill patients, oxygen consumption (VO2) and delivery (DO2) are used to determine optimal haemodynamic management and to grade severity of illness. VO2 may be measured by indirect calorimetry with metabolic gas monitoring systems or derived using the reverse Fick principle. Oxygen saturation (SaO2) may be measured directly by co-oximetry or derived by equations for incorporation into reverse Fick equations. A prospective study comparing VO2 measured by these methods was performed in 20 critically ill patients. The mean VO2 measured by the metabolic gas monitoring system (308 +/- 63.9 ml/min) was significantly greater than that measured by reverse Fick using measured SaO2 (284 +/- 72.0 ml/min) (P < 0.01). This difference may be due to intrapulmonary VO2. When SaO2 was calculated from three logarithmic equations and incorporated into the reverse Fick equations, calculated VO2's were significantly greater (P < 0.001) than those measured by indirect calorimetry. Correlation was poor and wide limits of agreement (-118 to +350 ml/min) were demonstrated. VO2 should ideally be measured by indirect calorimetry in the critically ill, or if reverse Fick is used, SaO2 should be measured by co-oximetry as the use of equations for clinical measurement of SaO2 is clinically suspect. PMID- 1463174 TI - Fibreoptic bronchoscopy in the critically ill: a prospective study of its diagnostic and therapeutic value. AB - AIM: A prospective study was undertaken to assess the diagnostic value and therapeutic usefulness of fibreoptic bronchoscopy in the critically ill. METHOD: Fifty-six bronchoscopies were performed in fifty patients. Biochemical, radiological, microbiological and clinical assessments were made before and after each procedure. RESULTS: Eighteen fibreoptic bronchoscopies were performed for therapeutic indications (32.1%) of which ten (55.6%) yielded a useful outcome. Thirty-eight bronchoscopies were for diagnostic purposes (67.8%) of which 22 (57.9%) were clinically useful. Broncho-alveolar lavage was performed in twenty eight cases (50%) and it led to a clinically useful diagnosis in 17 (60.7%). There was no major complication. A subgroup of patients was defined (persistent left lower lobe collapse or consolidation following thoracic or abdominal surgery) in whom fibreoptic bronchoscopy usually did not yield a useful outcome. CONCLUSION: The use of fibreoptic bronchoscopy in the Intensive Care Unit, in combination with the technique of broncho-alveolar lavage, results in a clinically useful outcome in the majority of cases. Fibreoptic bronchoscopy is an effective and safe diagnostic and therapeutic tool in critically ill patients. PMID- 1463175 TI - Septic shock: does adrenaline have a role as a first-line inotropic agent? AB - Fifteen adult patients, admitted to Baragwanath Hospital ICU with septic shock after adequate fluid loading and on no other inotropic agents, were given adrenaline in incremental doses. Oxygen transport and haemodynamic variables were monitored with each dose increment until a systolic blood pressure of 120 mmHg was obtained. This was reached on an average dose of adrenaline of 0.16 +/- 0.02 micrograms/kg/min. Mean arterial blood pressure increased by 22 +/- 2 mmHg mainly due to an increase in cardiac index (1 +/- 0.2 l/min/m2) and systemic vascular resistance index (130 +/- 41 dyn.s.cm.-5m-2) with a small increase in heart rate of 8 +/- 3 beats per minute. Oxygen delivery was increased with no significant increase in oxygen consumption and lactate levels increased. Adrenaline is therefore an effective initial inotropic agent. Patients may respond to lower doses than when used concurrently with other inotropic agents but there was still a significant dose variation in response. We cannot, however, exclude a deleterious effect on oxygen utilization. PMID- 1463176 TI - Total intravenous anaesthesia versus inhalational anaesthesia for dental day surgery. AB - Fifty young healthy and unpremedicated patients scheduled for removal of impacted teeth were randomly allocated to receive either total intravenous anaesthesia with propofol or conventional thiopentone/isoflurane/nitrous oxide anaesthesia. A double-blind postoperative assessment showed the former group to have a shorter reversal time and faster recovery of faculties, i.e. speech, memory as well as ability to sit up and walk without assistance (P < 0.01). There was no incidence of hypotension and of awareness in either group. The incidence of headache, nausea and vomiting was higher in the thiopentone/isoflurane/nitrous oxide group. PMID- 1463177 TI - Propofol induction for laryngeal mask airway insertion: dose requirement and cardiorespiratory effects. AB - The dosage, haemodynamic and respiratory effects of propofol for laryngeal mask airway (LMA) insertion were investigated. Fifty patients (ASA I-II) were randomly assigned one of four induction doses of propofol (1.5-2.5 mg/kg) delivered over 30 seconds and the first attempt at LMA insertion was made at 90 seconds. The LMA was inserted at 90 seconds in 35 patients and by 300 seconds in 13 others (mean plasma concentration at 90 seconds was 7.7 mcg/ml (no delay) versus 5.2 mcg/ml (insertion delayed), P < 0.01). Insertion was less successful after 1.5 mcg/kg (failed at 90 seconds in 6 of 12 patients), but did not vary with the other doses. Additional propofol (0.5 mg/kg/30s) was required in 22 patients for LMA insertion or to prevent movement, resulting in propofol concentrations at 120-180 seconds above 7 mcg/ml. Respiratory effects were minor, but MAP decreased by 18 +/- 1.4 mmHg at 90 seconds. Cardiovascular effects did not differ significantly between dosage groups or with the use of additional propofol. PMID- 1463178 TI - The incidence of bacteraemia following laryngeal mask insertion. AB - The incidence of bacteraemia following insertion of the laryngeal mask airway (LMA) was investigated in one hundred fit patients. Four cultures were positive: three represented contamination with skin flora; the other was a microaerophilic streptococcus grown from an anaerobic culture bottle. Although this organism can be pathogenic, it may also represent contamination. Our findings suggest that significant bacteraemia on insertion of the LMA is uncommon and is probably no more than with oral intubation. Antibiotic prophylaxis is of doubtful benefit in these circumstances. PMID- 1463179 TI - The effect of epidural blockade on postoperative hypercoagulability following abdominal aortic bypass surgery. AB - The effect of epidural blockade on postoperative hypercoagulability was assessed in patients undergoing elective abdominal aortic bypass surgery. Twenty patients were randomised to receive general anaesthesia alone, or general anaesthesia plus thoracic epidural blockade with 0.5% bupivacaine. It was found that the addition of epidural blockade did not alter the postoperative increase in plasma fibrinogen, factor VIII coagulant, or alpha 1-antitrypsin. Similarly, epidural blockade did not affect the postoperative decrease in antithrombin III. The results suggest that epidural blockade with local anaesthetic agents does not prevent the postoperative hypercoagulability response following abdominal aortic bypass surgery. PMID- 1463180 TI - Anaesthetic experience with cryotherapy for treatment of hepatic malignancy. AB - Hepatic cryotherapy is a relatively new technique, currently employed in the treatment of unresectable liver malignancy, which involves direct freezing of tumour deposits with liquid nitrogen. In a review of 26 patients undergoing this procedure, the anaesthetic considerations are defined. The total operation time ranged from 133 to 410 minutes. In spite of preventative measures, varying degrees of hypothermia occurred (range 33.7 degrees C to 36.5 degrees C), but no sequelae were encountered. Mean blood loss was 926 ml, and eleven patients required blood transfusion of between one and five units. There was a marked drop in platelet count associated with cryotherapy (mean fall of 123,000/mm3 by the second postoperative day). Following the procedure, fever and basal pulmonary atelectasis were common, while hypoglycaemia and renal impairment occurred on single occasions. Six patients underwent postoperative mechanical ventilation. Despite this, the mean hospital stay was under seven days. PMID- 1463181 TI - A clinical evaluation of the Hemocue haemoglobinometer using capillary, venous and arterial samples. AB - The 'Hemocue' device for rapid estimation of haemoglobin concentration was evaluated in a clinical setting. Repeatable accuracy of capillary, venous and arterial samples was examined and then compared with standard laboratory venous haemoglobin estimates using a 'Coulter JT' analyser in 42 patients. The mean values for haemoglobin (g/l) and coefficient of variation were capillary 108.2 (8.0); venous 104.9 (2.2); arterial 105.9 (2.0); and laboratory venous 104.6 (1.3). Although the mean haemoglobin values were similar, capillary samples were significantly less repeatable than venous or arterial samples (Pitman test, P < 0.001). Comparison of variance between the laboratory sample and each sampling technique demonstrated that capillary samples were significantly more variable than venous or arterial samples. Peripheral skin temperature did not influence the accuracy of capillary samples. Hemocue estimations of venous samples were found to be as accurate as laboratory estimations. The lack of repeatable accuracy of capillary estimations was sufficiently large that their use cannot be recommended in clinical practice. PMID- 1463182 TI - Fault in a Selectatec manifold resulting in awareness. AB - The Selectatec Vaporising System is a quick change system consisting of anaesthetic vaporisers of the Tec 3 and Tec 4 models and the compatibility manifold block on which these are seated on the anaesthetic machine backbar. There have been reports of difficulties with the seating and locking of the vaporisers which can cause a leak and failure of vapour delivery. The Faculty of Anaesthetists, Royal Australasian College of Surgeons (now Australian and New Zealand College of Anaesthetists) issued a hazard alert in March 1991 drawing attention to this potential fault. We present two cases of awareness associated with failure of internal seals within a Selectatec compatibility manifold block which did not have a detectable leak. PMID- 1463183 TI - Ondansetron: indications and applications in the paediatric intensive care unit. PMID- 1463184 TI - Diltiazem overdose in an elderly patient: efficacy of adrenaline. PMID- 1463185 TI - Bilateral phrenic nerve palsy following cardiac surgery in a diabetic patient. PMID- 1463186 TI - Extensive central neural blockade following interscalene brachial plexus blockade. PMID- 1463187 TI - Accidental intra-arterial flucloxacillin: management using guanethidine. PMID- 1463188 TI - The laryngeal mask in the management of a paediatric difficult airway. PMID- 1463190 TI - Transcutaneous cardiac pacing for asystole during permanent pacemaker lead repositioning. PMID- 1463189 TI - Prolonged malignant hyperthermia in the absence of triggering agents. PMID- 1463191 TI - Acute cord prolapse in an obstetric patient with myotonia dystrophica. PMID- 1463192 TI - The Selectatec system: another cause of total leakage. PMID- 1463193 TI - CO2 sensor design fault. PMID- 1463194 TI - Lignocaine suppositories for migraine. PMID- 1463195 TI - Aspiration and the laryngeal mask airway--a survey of Australian intensive care units. PMID- 1463196 TI - Laryngoscopy through the LMA--a useful skill to acquire. PMID- 1463197 TI - Positioning endotracheal tubes. PMID- 1463198 TI - Tube in the trachea? PMID- 1463199 TI - Positioning double-lumen tubes. PMID- 1463200 TI - Endobronchial intubation during laparoscopic cholecystectomy. PMID- 1463201 TI - Anaesthetic problems during laparoscopic cholecystectomy. PMID- 1463202 TI - Beta-blockade or magnesium in organophosphorus insecticide poisoning (OPIP) PMID- 1463203 TI - Misplaced subclavian line. PMID- 1463204 TI - Dantrolene sharing. PMID- 1463205 TI - Cessation of smoking following tape suggestion under anaesthesia. PMID- 1463206 TI - Hospital admission from a day surgery unit. PMID- 1463207 TI - Day surgery admissions. PMID- 1463208 TI - Cardiac output alters uptake of inhaled anaesthetics. PMID- 1463209 TI - Peribulbar anaesthesia for intraocular surgery. PMID- 1463210 TI - Fit with finger block. PMID- 1463211 TI - Environmental analytical chemistry: a continuing frontier. PMID- 1463212 TI - Environmental carcinogens: in vivo monitoring using GC/MS. PMID- 1463213 TI - Elimination of electrooxidizable interferant-produced currents in amperometric biosensors. AB - Electrooxidizable ascorbate, urate, and acetaminophen that interfere with amperometric glucose assays are completely and rapidly oxidized by hydrogen peroxide in a multilayer electrode. The multilayer electrode is composed of an immobilized, but not electrically "wired", horseradish peroxidase (HRP) film coated onto a film of electrically "wired" glucose oxidase (GO). The "wired" enzyme is connected by a redox epoxy network to a vitreous carbon electrode. The current from the electrooxidizable interferants is decreased by their peroxidase catalyzed preoxidation by a factor of 2500, and the glucose/interferant current ratio is increased 10(3)-fold. Undesired electroreduction of hydrogen peroxide can result when HRP is also "wired" to the electrode. Such unwanted "wiring" is prevented by incorporating an electrically insulating barrier layer between the wired GO film and the HRP film. The hydrogen peroxide necessary for elimination of interferants can be added externally, or when this is not possible, it can be generated in situ by means of a coupled enzyme reaction. PMID- 1463214 TI - Influence of tyrosine on the dual electrode electrochemical detection of copper(II)-peptide complexes. AB - The bluret reaction makes peptides electrochemically active. This is the basis of an electrochemical method for the detection of peptides following their liquid chromatographic separation. This paper discusses the influence of tyrosine, an electroactive amino acid, on the detection of Cu(II)-peptide (bluret) complexes containing it. The dual electrode detector has an upstream anode and a downstream cathode. Tyrosine-containing peptides yield anodic signals that are approximately the sum of the tyrosine signal and the signal from the bluret complex of a nonelectroactive model peptide, phenylalanylglycyl-glycine (FGG). The cathodic signal is depressed in comparison to FGG. This is traced to the presence of an intramolecular reaction between Cu(III) and a reaction product resulting from the oxidation of the tyrosinyl residue. The rate constant for the corresponding intermolecular reaction is significant (10(6)-10(7) M-1 s-1), but in practical analytical situations, the concentrations of the reactants will be small, so the reaction will not be a major factor. Sensitivities for several bioactive peptides are reported. The dependence of the signals on the position of tyrosine in a tripeptide is also studied. PMID- 1463215 TI - Determination of aluminum by chemical and instrumental neutron activation analysis in biological standard reference material and human brain tissue. AB - Since aluminum is an extremely difficult element to determine reliably in biological samples, no National Institute of Standards and Technology (NIST) biological standard reference material for tissue has yet been certified for aluminum. A chemical neutron activation analysis procedure employing anion exchange chromatography was developed. The procedure proved successful in decontaminating radioactivatable sodium and chlorine and phosphorus which can produce aluminum via a fast neutron bombardment. For bovine liver (NIST SRM 1577 a) a value of 2.1 +/- 0.2 micrograms of aluminum/g of sample was determined, comparing favorably to the uncertified value 2 micrograms/g sample. For freeze dried urine (NIST SRM 2670) a value of 0.18 +/- 0.01 micrograms of aluminum/mL of urine was observed. Its uncertified value is 0.18 micrograms of aluminum/mL of sample. Twenty three individual samples in three different human brains were analyzed for their aluminum content. PMID- 1463216 TI - Organized media for fluorescence analysis of complex samples: comparison of bile salt and conventional detergent micelles in coal liquids. AB - Accurate quantitative determinations are often difficult to obtain from fluorescence analysis of complex samples due to sample matrix effects and intermolecular interactions between solutes. Organized media can be used to minimize these unwanted processes without physical separation or extraction of the analytes from the sample matrix by isolating the analyte molecules in a uniform microenvironment within the sample. The advantages of bile salt micellar media over conventional detergent micelles are demonstrated for analysis of coal liquids. The bile salt media is shown to increase the sensitivity and dynamic range of fluorescence measurements relative to simple ethanolic solutions, without promoting gound-state and excited-state interactions that occur in the detergent micellar media. PMID- 1463217 TI - Integrated approach to surfactant environmental safety assessment: fast atom bombardment mass spectrometry and liquid scintillation counting to determine the mechanism and kinetics of surfactant biodegradation. AB - Fast atom bombardment mass spectrometry and liquid scintillation counting have been used to study the biodegradation of a novel cationic surfactant in live sludge. The rates of primary biodegradation and the extent of complete mineralization were determined. Furthermore, an intermediate degradation product was identified and its rates of formation and subsequent removal have been established. These data find utility in assessing the environmental safety of the surfactant and the accuracy of various environmental fate models. PMID- 1463218 TI - Fast atom bombardment tandem mass spectrometric identification of diacyl, alkylacyl, and alk-1-enylacyl molecular species of glycerophosphoethanolamine in human polymorphonuclear leukocytes. AB - Fast atom bombardment ionization with tandem mass spectrometry of both positive and negative ions is a useful technique for the identification of intact glycerophosphoethanolamine (GPE) phospholipids, providing information as to polar head group and fatty acyl substituents. In the identification of GPE molecular species, positive ion neutral loss scanning for 141 units was attempted to confirm the presence of the phosphoethanolamine polar head group. This scan was found to discriminate against the abundant subclass of phospholipids having an 1 O-alk-1'-enyl linkage, termed plasmalogens, as well as 1-O-alkyl ether species. The neutral loss process is suggested to involve attack of a carbonyl oxygen from either sn-1 or sn-2 on the sn-3 methylene carbon with loss of neutral phosphoethanolamine. Using FAB/MS/MS alone, it is not possible to differentiate between plasmalogens and other 1-O-alkyl ether molecular species having the same molecular weight. The combination of mild acid hydrolysis, which selectively hydrolyzes the labile 1-O-alk-1'-enyl bond, with subsequent FAB/MS/MS distinguished species of these distinct subclasses. Using these techniques and precursor ion scans for the arachidonoyl carboxylate anion, m/z 303, the arachidonic acid containing glycerophosphoethanolamine molecular species were identified and the relative abundance of arachidonoyl plasmalogen, alkylacyl, and 1,2-diacyl GPE molecular species in the human polymorphonuclear leukocyte (neutrophil) was determined to be 75.4%, 12.1%, and 12.5%, respectively. These values were not significantly different from that reported in the literature using conventional methodology. PMID- 1463219 TI - Separation of closely related large peptides by micellar electrokinetic chromatography with organic modifiers. AB - Large peptides with similar electrophoretic mobilities were separated by micellar electrokinetic chromatography (MEKC) with organic modifiers. [Leu13]motilin and [Met13]motilin differ by only one neutral amino acid residue. Because the electrophoretic mobilities of these peptides are almost identical, these peptides were not separated by capillary zone electrophoresis (CZE). Such large peptides have not been separated by conventional MEKC either, because they interacted strongly with the micelle. However, they were completely separated by MEKC when an organic solvent was added to the micellar solution. Some insulins, larger peptides than motilin, from different origins, which have very similar electrophoretic mobilities, were also successfully separated by the same technique. The size of peptides which were separated without organic modifiers was examined. PMID- 1463220 TI - Microtiter plate binding assay for cholinergic compounds utilizing the nicotinic acetylcholine receptor. AB - A receptor-based binding assay for the determination of cholinergic compounds of the nicotinic acetylcholine receptor has been developed. By conducting the assay in a 96-well microtiter plate, the method is suitable for large-scale screening in drug development. Solid-phase extraction of the enzyme label significantly simplifies the assay protocol compared to earlier methods. The assay is based on immobilization of biotin-BSA on the microtiter which takes up avidin-labeled peroxidase due to avidin-biotin interaction. To perform the assay, a ligand (the analyte) and a biotin alpha-bungarotoxin conjugate (alpha Bgt-biotin) sequentially bind to a vesicle bound nicotinic acetylcholine receptor. This is done either in a test tube, assay I, or in a biotinylated microtiter well, assay II. Avidin-HRP is then added to this mixture; free alpha Bgt-biotin conjugate and immobilized biotin-BSA compete for the avidin sites. After the assay solution has been aspirated off, bound enzyme activity is determined which is directly related to the amount of alpha Bgt-biotin added. Dose-response curves of cholinergic compounds and Scatchard plots were generated to evaluate the apparent binding constants. Kinetic studies were conducted for the purpose of optimization. The final assay can be performed in under 4 h with a minimum of sample handling. PMID- 1463221 TI - Chiral separation of leucovorin with bovine serum albumin using affinity capillary electrophoresis. AB - A method for the determination of the (6R)- and (6S)-stereoisomers of leucovorin using electrokinetic chromatography (EKC) in the affinity mode has been developed. Bovine serum albumin (BSA) is used as a run buffer additive to incorporate enantiomeric selectivity into the system. Protein-wall interactions are minimized by using a poly(ethylene glycol) (PEG) coated capillary. Chiral resolution is obtained in 12.5 min with efficiencies greater than 200,000 theoretical plates using BSA as an additive, while no resolution is obtained in the absence of BSA. A general equation is derived to calculate the free energy of interaction between the leucovorin isomers and the BSA molecule. This method represents a new means of obtaining thermodynamic data for substrate binding interactions and for the general study of drug cross-reactions and interactions of drugs with serum and other proteins. PMID- 1463222 TI - Separation and identification of DNA-carcinogen adduct conformers by polyacrylamide gel electrophoresis with laser-induced fluorescence detection. AB - We have developed a separation protocol utilizing high-resolution polyacrylamide gel electrophoresis (PAGE) to isolate stable anti-benzo[a]pyrene diol epoxide adducts of oligodeoxynucleotides. Both enantiomers produced multiple adduct species. The distribution of adduct types could be quantitated by densitometry of autoradiograms or Cerenkov counting of eluted oligomers modified by anti-BPDE isomers. Laser-induced fluorescence (LIF) spectra of eluted adducts at 4.2 K (fluorescence line-narrowing spectroscopy) and 77 K revealed that bands corresponded to pure conformers of pyrene chromophore. Carcinogen-modified oligodeoxynucleotides were single-stranded, but there were often considerable stacking interactions between the pyrenyl residues and the oligonucleotide bases, indicating that electrophoresed oligomers were single-stranded but in a native, versus random coil, conformation. The ability to identify and quantitate adducts by PAGE-LIF, coupled with the high resolution and sensitivity of both techniques, makes PAGE and LIF in tandem a potentially powerful tool in the study of chemical carcinogenesis or other ligand-DNA interactions. PMID- 1463223 TI - Quantitative determination of native proteins in individual human erythrocytes by capillary zone electrophoresis with laser-induced fluorescence detection. AB - Intracellular fluid within single human erythrocytes is analyzed by capillary electrophoresis with laser-excited native protein fluorescence. Good signal-to noise is achieved, allowing even minor components to be quantified. Non-Gaussian distributions were found for total protein, fraction carbonic anhydrase, fraction hemoglobin A0, and an unidentified component. Variations among a group of 29 cells for each quantity are as much as 1 order of magnitude, even though erythrocytes are known to be fairly homogeneous in size distribution. Variations in fraction hemoglobin A0 reflect differences in in vitro oxidation rates to methemoglobin. A positive correlation was observed between carbonic anhydrase and hemoglobin A0 for individual cells. This is consistent with the presence of erythrocytes of different ages within the population, with the older cells being less capable of maintaining enzyme activity and preventing oxidative damage. PMID- 1463224 TI - Secondary ion emission from solutions: time dependence and surface phenomena. AB - The temporal behavior of FAB mass spectra from glycerol solutions of tetradecyltrimethylammonium bromide (C14H29-N(CH3)3Br, TTAB) and tetraethylammonium iodide (TEAI) was investigated. FAB spectra of the TTAB solution displayed a continuous decrease in TTA+ with time. Spectra obtained from the TEAI solution were initially invariant for several minutes and then displayed a gradual increase in the relative abundance of TEA+ to a maximum, followed by a precipitous drop in ion intensity. Secondary ion images of droplets of TTAB solution showed that emission of both TTA+ and glycerol secondary ions was homogeneous across the sample. Secondary ion images of droplets of TEAI solution showed heterogeneous and segregated emission of both TEA+ and protonated glycerol. Results from the FAB spectra and the secondary ion images were correlated and rationalized on the basis of surface tension-induced mass transport and matrix evaporation. PMID- 1463225 TI - [A comparison of the determination of cardiac output by the Fick method and by thermodilution during heart surgery]. PMID- 1463226 TI - [The effect of the partial pressure of O2 in arterial blood on O2 consumption by patients during artificial circulation]. PMID- 1463227 TI - [Practical aspects of cardioplegia]. AB - Concentrations of the ingredients have been analysed in a nonstandard cardioplegia solution (CS) and CS from St. Thomas Hospital at the outset before CS introduction into the coronary vessels of patients under cardioplegia. It has been shown that the use of nonstandard CS was accompanied by undesirable variability in ingredient concentration, which to some extent may be accounted for by the use of incompletely unfrozen CS. The use of CS from St. Thomas Hospital could be accompanied by moderate hypermagnesiumemia, which did not lead to the onset of vascular insufficiency. It is stressed that plasma magnesium content should be controlled when this CS is used. PMID- 1463228 TI - [The effect of agonists and antagonists of opiate receptors on the activity of the kallikrein-kinin system in hemorrhagic shock]. AB - Mean blood pressure and heart rate have been registered in the experiments on male Wistar rats. Kallikrein-kinin system (KKS) components have been evaluated in blood plasma: plasma kallikreinogen, kallikrein-inhibiting capacity, spontaneous esterase activity. The parameters were determined before and after hemorrhage in the volume accounting for 10, 20 and 30% of the circulating blood volume. The rats were administered enkephalin analogues--DAGO, DADL and naloxone. The administration of mu-agonist DAGO improved hemodynamics. DAGO effect was eliminated by naloxone. The administration of enkephalins did not affect KKS parameters, while naloxone potentiated KKS changes induced by hemorrhage. It has been shown that KKS is not involved into the mechanism of hemodynamic changes in response to enkephalin administration during hemorrhagic shock. PMID- 1463229 TI - [The use of ultra-high doses of insulin for the treatment of severe heart failure during cardiosurgical interventions]. AB - The experience is reviewed on the use of superhigh insulin doses 1200 to 3800 U (31.4 +/- 5.3 U/kg) for the treatment of acute heart failure in 17 patients subjected to open heart surgery. Symptoms of heart failure refractory to catecholamines and vasodilators were accompanied by marked hyperglycemia (23.1 +/ 4.3 mmol/l). It was impossible to discontinue assisted circulation. In 82.3% of patients myocardial contractility upon insulin administration improved considerably, which led to discontinuation of assisted circulation with moderate inotropic support. Possible mechanisms ensuring the efficacy of massive insulin therapy in patients with acute heart failure are discussed. PMID- 1463230 TI - [The clinical picture of non-traumatic apallic syndrome]. AB - Clinical signs of non-traumatic apallic syndrome (AS) are caused by universal necrosis of the brain cortex, with the brain stem remaining intact. The reasons of AS are heart and respiration arrest, stable collapses of various genesis, vascular brain diseases. Management was ineffective. Strict AS prevention is necessary, i.e. timely and expert cardiorespiratory resuscitation. Intensive care and cardiorespiratory resuscitation are not recommended in patients with vast brain infarction secondary to brain vascular diseases. PMID- 1463231 TI - [The clinical significance of studying central hemodynamics in patients during extracorporeal detoxification]. PMID- 1463232 TI - [The role of humoral factors in the pathogenesis of the postoperative syndrome]. AB - Blood plasma levels of "pain substances" (serotonin, histamine, prostaglandin F2 alpha, adrenaline /A/) and neuropeptides (beta-endorphin, somatostatin) have been evaluated in 39 patients during the early postoperative period after lung and mediastinum surgery. The studies have shown that the content of these biologically active substances increases considerably. Following stellate ganglion blockade A concentration decreased significantly, the uptake of narcotic analgesics used for postoperative analgesia reduced 1.7-fold, however the levels of "pain substances" and neuropeptides remained unchanged. It is believed that postoperative pain syndrome develops due to the elevation of the levels of the substances under study. Stellate ganglion blockade produces only sympatholytic effect, which shows the necessity of the elaboration of drug therapeutic techniques blocking "pain" receptors and using "pain substance" antagonists. PMID- 1463233 TI - [Tracheobronchial obstruction and general anesthesia in patients with mediastinal tumors]. PMID- 1463234 TI - [The status of indices of immunity and hemostasis in patients with lung cancer and their changes due to general anesthesia and surgical trauma]. AB - Phagocytosis, some factors of humoral immunity and hemostasis have been studied in cancer patients before and after surgery. Suppression of natural body resistance in the preoperative period, as well as significant inhibition of leukocyte phagocytic activity following surgery and anesthesia have been established. A correlation has been suggested between hemostasis damages in the postoperative period and an elevated IgM concentration. PMID- 1463235 TI - [The use of fatty emulsions in the postoperative period in cardiosurgical patients with kidney failure]. AB - The data are presented on the use of fatty emulsions for parenteral nutrition of 68 cardiosurgical patients with renal failure in the postoperative period. It has been established that intravenous administration of fatty emulsions ensures up to 50% of an overall daily calories uptake, with the infusate volume restricted considerably, helps stabilize energy and nitrogen body balance and reduces the risk of complications associated with hyperosmolality and hyperglycemia. PMID- 1463236 TI - [The status of intracellular metabolism during intensive therapy of severe surgical endotoxicosis]. AB - Introduction of separation plasmapheresis and plasmasorption into intensive therapy of 60 patients with surgical endotoxemia ensured marked detoxication, which manifested in earlier improvement of the clinical symptoms and normalization of intracellular metabolism in cellular elements of the peripheral blood. The data obtained make it possible to recommend the use of the above treatment procedures for elimination of profound intracellular metabolic disturbances in the postoperative period. PMID- 1463237 TI - [A comparative evaluation of the efficacy of the traditional combination of high frequency and intermittent high-frequency artificial ventilation of the lungs in patients with parenchymatous acute respiratory insufficiency]. AB - Conventional controlled lung ventilation (CLV) with positive end expiratory pressure (PEEP) (Con CLV), combined high-frequency CLV (Com HF CLV) and intermittent high-frequency CLV with PEEP (Int HF CLV) have been performed in 43 patients with parenchymatous acute respiratory failure (ARF). It has been established that Int HF CLV significantly increases PaO2 in patients with focal damages of the lung parenchyma and effective compliance (Ceff) > 0.033 l/cm H2O. Com HF CLV increases significantly PaO2 and lung compliance in patients with disseminated lung damages and Ceff < 0.030 l/cm H2O and has marked consequences. Different efficacy of various types of HF CLV under study may be to some extent accounted for by different intraalveolar maximum pressure, which (as it has been shown on the lung model) is higher in Com HF CLV and lower in Con CLV and Int HF CLV. PMID- 1463238 TI - [Auxiliary extracorporeal and hyperbaric oxygenation in the combination treatment of severe exotoxic shock]. AB - Extracorporeal blood oxygenation makes it possible to stabilize blood circulation, improve gas exchange in severe exotoxic shock, perform blood replacement with small volume of donor blood and continue etio-pathogenetic treatment of patients with severe poisoning with acetic essence and methemoglobin forming poisons. Hyperbaric oxygenation in the early postperfusion period decreases oxygen debt, improves intravenous glucose utilization, providing adequate energy supply. Extracorporeal and hyperbaric oxygenation added to the therapeutic complex improves by half the clinical efficacy of resuscitation and intensive care. PMID- 1463239 TI - [The effect of hemosorbents on the structure of polymorphonuclear leukocytes in man]. AB - The effect of various hemosorbents (HS)--carbon and textile--on the structure of neutrophils has been studied in vitro. It has been shown that the mechanism of cell degranulation is universal on various HS and does not depend on the anticoagulant used or on blood donor diseases. The degree of degranulation both for primary and for secondary granules increases with the prolongation of blood contact with HS, directly depends on HS--blood ratio and is determined mainly by the type of HS: degranulation on textile HS is considerably greater than that on carbon HS. Degranulation was confirmed by elevated blood plasma concentration of lactoferrin, a specific marker of secondary neutrophil granules. It is suggested that cell degranulation on HS leading to a considerable posthemosorption increase in the blood plasma level of biologically active intracellular components is essential in the process responsible for correcting hemosorption effect in different diseases. PMID- 1463240 TI - [General anesthesia during surgery of breast cancer]. AB - In 1982-1989 intravenous anesthesia was performed to 1160 patients operated on for breast cancer. Intravenous analgesia has a number of advantages over endotracheal anesthesia. The analgesic techniques have been compared. Absence of complications in the operative and postoperative periods, prompt recovery of the patients' physical and psychic activity following intravenous anesthesia make it a method of choice for surgical treatment of cancer patients who require no myorelaxation. PMID- 1463241 TI - [The prospects of using dopamine as an antishock preparation]. AB - The quantitative evaluation of the centralization reaction for shockogenic trauma has been experimentally established as an objective criterion of circulatory homeostasis failure severity and adequacy of its correction. The highest antishock effect of dopamine is reached when cardiac output fraction addressed to thoracic region vitals is supported by dopamine on the 43-45% level. Single infusion of the new synthesized prolonged dopamine (12.5 mg/kg) supplies hemodynamic stabilization for post-trauma hypovolemia during 4 hours. PMID- 1463242 TI - [Functional disorders of the autonomic nervous system during severe poisoning by clophelin in children]. AB - Disturbances in autonomic nervous system function have been studied during clofelin poisoning in children. A correlation has been established between changes in autonomic homeostasis and reduction in body temperature, bradycardia and arterial hypotension. The studies of cortisol blood level suggests two phases of poisoning: primary (specific) vagotonic phase and secondary (nonspecific) hypersympaticotonic phase. Changes in autonomic homeostasis accounted for the use of atropine sulfate for specific (antidote) therapy. PMID- 1463243 TI - [Plasmapheresis in the combination treatment of toxic diphtheria in children]. PMID- 1463244 TI - [Evaluation of the uptake of crystalline amino acid preparations based on the concentration of urea in the blood and tissues]. AB - The assimilation of polyamine, levamine and "new" alvesin has been experimentally assessed by blood and tissue urea concentrations. It has been established that polyamine was best assimilated and was followed by levamine and "new" alvesin. PMID- 1463245 TI - [Complications associated with the use of protamine sulfate]. PMID- 1463246 TI - [Reasons for the failures of hemosorption and thrombogenic complications of hemosorption during the venovenous method of setting up the extracorporeal system]. PMID- 1463247 TI - [Transcutaneous transtracheal jet ventilation]. PMID- 1463248 TI - [Editorial symposium. Varicose disease of the lower limbs. Presentation of the subject]. PMID- 1463249 TI - [Definition and etiopathogenesis of varicose veins]. PMID- 1463250 TI - [Differential diagnosis of phlebedema and lymphedema]. PMID- 1463251 TI - [Instrumental diagnosis of varicose veins]. PMID- 1463253 TI - [Elastic compression in varicose disease]. PMID- 1463252 TI - [Varicose disease: pharmacological treatment]. PMID- 1463254 TI - [Surgical treatment of varices and their complications]. PMID- 1463255 TI - [Multifactorial surgical risk index of the development of respiratory complications]. AB - Respiratory events are between the most frequent postoperative complications. The preoperative conditions associated with postoperative respiratory failure were evaluated in a prospective study of 1182 patients from six Italian Surgical Units. Multiple regression logistic analysis was employed for statistical evaluation and a predictive prognostic score was derived. Only the presence of the following conditions was significant in affecting postoperative respiratory outcomes: preoperative respiratory and cardiac failure, hypotransferrinemia, prolonged surgical procedures (above the 2 hours) and peroperative bacterial contamination. Advanced age did not appear as a major risk factor. Studies on the predetermination of the pulmonary complications have been widely published. Historical risk factors include the presence of respiratory disease, smoking habits, obesity and thoracic or upper abdominal surgical procedures. Although the results of the present study need a prospective confirmation, the predictive scoring system proves to be a usefull tool that can be employed in most of the General Surgery Units. PMID- 1463256 TI - [Tumors of nerve sheaths of the peripheral nerves]. AB - Objectives of this paper are the analysis of the confidence in the complementary investigation for the differential diagnostic between schwannoma and neurofibroma, and the retrospective evaluation of the therapy based on the consequent follow-up. The study has been conducted on 36 patients, most of them observed by University Clinic of Navarra (Pamplona), and the others by N. Picardi, all with preoperative diagnosis of schwannoma and neurofibroma, localized in 13 cases in peripheral nerves. Diagnostic iter, pathologic definition, therapy and evolution has been evaluated for all of them. In conclusion we feel that this pathology has to be suspected every time we find a tumor with neurologic symptomatology and that surgical indication of exeresis is the most correct in the majority of cases; moreover imaging investigations is rather useful, but if any doubt occurs we must proceed to biopsy or directly to exeresis of the tumor. Our experience shows that schwannoma, thanks to its anatomic patterns, can be treated less radically toward the nerve continuity than neurofibroma, and that the technique of nerve graft could be a useful alternative in this kind of surgery. PMID- 1463257 TI - [Complications of gastroesophageal reflux: considerations on a non-selected case series]. AB - According to the experience of the authors on a non-selected case report, pharmacologic progresses in the therapy of various aspects of peptic disease permit an ease management also of gastro-esophageal reflux disease. Moreover, endoscopy is the very modern pivot of conservative treatment of more severe complications as strictures are, through repetitive and progressive instrumental dilatations. The surgical treatment of the most severe and intractable eveniences must be chosen for only a low percentage number of patients, after a careful functional analysis of the single case. Very important is the endoscopic and histologic control of Barrett esophagus and severe dysplasia. PMID- 1463258 TI - [Cholelithiasis after total gastrectomy for gastric cancer]. AB - After gastric resection for peptic ulcer and total gastrectomy for Zollinger Ellison syndrome, there is an increased prevalence of cholelithiasis. In order to assess whether this increased prevalence also exists after total gastrectomy for cancer, we evaluated the rate of cholelithiasis (echographic diagnosis) both before and after this operation. Between 1980 and 1990, 89 patients underwent total gastrectomy for cancer in the Surgical Department of our Institute. The pre operative prevalence of gallstones was 5% in the males and 13.8% in the females. Seventy-four of the eighty-nine patients (83%) were examined post-operatively (7 patients with pre-operative cholelithiasis, 3 who died during the post-operative stay and 5 lost to follow-up were excluded from the study). The median post operative follow-up was 24 months (range 3-115 months). The post-operative prevalence of cholelithiasis in the 74 patients was 39.6% in the males and 19% in the females. We also calculated the expected frequency of gallstones in both the pre- and post-operative groups from prevalence data in the population of the city where our Institute is based (taken from an echographic survey). We then compared the observed frequency of cholelithiasis with the expected frequency and we found that the difference in pre-operative frequencies, both in the males and females, was not statistically significant (p > 0.05). The same was true of the post operative frequencies in the females (p = 0.48), but in the males there was a statistically significant difference between the observed frequency of cholelithiasis and that expected after total gastrectomy (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463259 TI - [Preoperative staging of gastric carcinoma using endosonography (EUS)]. AB - Accurate staging of gastric malignancy can only be obtained at surgery and after detailed histological examination of the resection specimen. Endoscopic ultrasonography may provide accurate detection and staging of gastric cancer because of its ability to visualize both the intramural and extramural extent of the lesion and any adjacent lymph node involvement. From february 90 to april 91, 29 patients with a gastric carcinoma were studied endosonographically before surgery. All studies were performed with an Olympus EU-M3. Preoperative TNM classification and a prediction of the resectability of gastric cancer were done in every patient. The results were matched with those obtained with the histology of resected specimens according to the TNM classification 1987. Endoscopic ultrasonography was accurate in assessing the extent and depth of tumor infiltration. The overall accuracy rate was 90.5% (19 out of 21 patients). Overstaging occurred in 9.5% of the cases (2 patients); none understaging occurred. EUS was less accurate in assessment of lymph node metastasis; the overall accuracy rate was 57.1%. Distinction between reactive lymph node and small micrometastatic lymph node involvement could be hard. Local resectability was correctly diagnosed with EUS in each of 23 patients; in two patients an intramural mass with a deep infiltration into the surrounding tissue was correctly diagnosed. In our opinion EUS is an essential diagnostic procedure in the clinical staging of the gastric cancer. PMID- 1463260 TI - The simultaneous presence of primary lymphoma and adenocarcinoma in the stomach. AB - The authors describe a rare case, recently observed by them, of coexisting primary lymphoma and adenocarcinoma of the stomach. After illustrating the more salient aspects of the clinical and anatomopathological pattern, the Authors discuss the general issue of the simultaneous presence of the two pathologies, analysing in particular their classification and etiopathogenic aspects. They then discuss the peculiar aspects of the case considered, including the preoperative diagnosis of non-Hodgkin gastric lymphoma, and highlight the fact that, unlike what is more frequently reported in the literature, the carcinomatous component had been completely ignored. As a final consideration, they stress the importance of studying this rare combination of tumoral components in order to gain a better understanding of oncogenic mechanisms so far unknown. PMID- 1463261 TI - [Ileal diverticula: apropos of a case]. AB - The authors report a case of abdominal aortic aneurysm surgically treated. At surgical exploration an ileal diverticulum was discovered. A 15 cm ileum tract was hyperemic and oedematous. The abdominal aortic aneurysm was resected and an aorto aortic graft implanted. The retroperitoneal space was carefully closed and then the diverticulum resected and an end-to end intestinal anastomosis performed. An etiological review of this pathology was done identifying two possible causes: true and false diverticula. The true diverticulum is a congenital lesion involving the 3 layers of the intestinal wall. On the contrary the false diverticulum is acquired and generally develops on the mesenteric site due to a pulsion mechanism. The wall involves the mucosa and serosa layers only. Diagnosis is often done during abdominal exploration for other cause (as in our case) or for complicated diverticula. Preoperative radiologic diagnosis is rare and doesn't always require surgical treatment. PMID- 1463262 TI - [Ogilvie's syndrome: clinical reality or nosographic error?]. AB - The authors report their experience in the management of Ogilvie's syndrome, a rare form of large bowel acute pseudo-obstruction. The study includes fifteen cases of the disease. There were ten males and five female, with a mean age of sixty-two years (range 45-92). Three patients were only treated with medical and conservative measures, one with unsuccessful colonoscopy and twelve (two with colonic perforation) underwent laparotomy. The surgical procedures performed were tube cecostomy (40%), colonic resection with primary anastomosis (27%) and exploratory laparotomy with decompression (13%). The overall morbidity and mortality rate were respectively 0 and 13%. Our epidemiological, clinical and therapeutic results are similar to those reported in the international literature. The pathophysiology of the syndrome is still unknown. It can be "idiopathic" or can complicate other diseases or surgical procedures (urological and gynaecological procedures mostly). Plain abdominal roentgenogram is the most useful diagnostic test, but colonoscopy may be an alternative diagnostic (and therapeutic) weapon. Conservative treatment is the method of choice but when the cecal diameter is more than 12 cm. (impending perforation), when the colon is perforated or when medical measures are unsuccessful, surgical procedure is compulsory. The age of the patient, cecal size, delay in colonic decompression are the most important prognostic factors. Even with a proper management, the prognosis is severe and the mortality rate is high (3-50%). PMID- 1463263 TI - [Carcinoma of the cecum: is early diagnosis possible?]. AB - Between 1982 and 1989, a consecutive series of 34 patients with cancer of the cecum were operated in our hospital. Overall, at 5 years the survival was 50%. We did not notice any correlation among symptom duration and survival. Patients admitted in the asymptomatic phase had the best survival rate (66.6%). Our study suggest that only neoplasm diagnosed in asymptomatic patients and treated promptly are related to a good survival rate. We, therefore, emphasize the importance and the necessity to investigate all patients with a suspected cecum cancer by means of colonoscopy. PMID- 1463264 TI - [Intestinal recanalization 16 years after Hartmann's operation]. AB - The authors report a case of a surgical intestinal recanalization after 16 years since a Hartmann's intervention. After some considerations on the results they obtained in similar cases, the Authors call attention on this specific clinical case. They come to the conclusion that a successful surgical recanalization- although the difficult availability of the remaining rectal stump--is possible even if a long period has passed since a Hartmann's intervention was performed. In fact the rectal stump and the sphincter apparatus, even if excluded from the fecal transit for a long while, retain largely their specific functional activities and show a marked ability for an effective sensitive-motor restoration. PMID- 1463265 TI - [Rare colonic occlusions: volvulus of the splenic flexure]. AB - Authors report a case of perforated splenic flexure volvulus, treated with resection, end colostomy and closure of the distal stump. From the revision of literature it comes out the case reported is the 30th recorded till now, the 6th with ischemic complications, and the only one with perforation. Actual pathogenetic trends and various therapeutic options are reported. PMID- 1463267 TI - Bibliographic information retrieval. PMID- 1463266 TI - [Radical excision and primary suture of pilonidal sinus: our experience]. AB - Various operations could be used for pilonidal sinus disease. The authors report their experience, discuss the etiopathogenesis (acquired or congenital origin) describe their method of treatment and results and compare them with those of the other reviews. PMID- 1463268 TI - Posttranslational processing of the neurotensin/neuromedin-N precursor. PMID- 1463269 TI - Actions of neurotensin: a review of the electrophysiological studies. AB - Three effects of NT were observed on midbrain DA cells. The modulatory effect of NT, that is, the attenuation of DA-induced inhibition, has been most extensively examined. Studies indicate that this effect of NT was not simply due to a nonspecific excitation. NT selectively attenuated DA-induced inhibition without affecting either GABA-induced inhibition or glutamate-induced excitation of the same cells, and the attenuation of DA-induced inhibition could be observed at the doses at which the basal activity of DA cells was not changed by NT. The attenuation of DA-induced inhibition by NT is also unlikely to result from the formation of a DA-NT complex, since neuromedin N, which competes with NT for the same receptor but does not bind to DA, mimicked the effects, and neurotensin(1 11), which forms a complex with DA but is inactive in competing for NT receptors, did not. The similarities between the effects of NT and those of 8-bromo-cAMP and forskolin suggest that intracellular cAMP and protein kinase A may be involved. This suggestion was supported by the findings that IBMX (an inhibitor of phosphodiesterases) potentiated the effect of NT; and SQ22536 (an inhibitor of adenylate cyclase) and H8 (an inhibitor of protein kinase A) antagonized it. Phorbal-12,13-dibutyrate (an activator of protein kinase C) did not mimic the effect of neurotensin, and H7 (an inhibitor of protein kinase C) did not reduce the effect, suggesting that protein kinase C is unlikely to be involved in the modulatory effect of neurotensin. Experiments in vitro indicated that the excitatory effect of NT on DA cells occurred at higher concentrations (> 10 nM) than those needed for producing the modulatory effect. Its persistence during DA receptor blockade by sulpiride suggests that this effect was not entirely mediated by an attenuation of the inhibition induced by endogenously released DA. At even higher concentrations (> 100 nM), a sudden cessation of cell activity preceded by an increase in firing rate was observed. Whether this effect of NT was due to depolarization inactivation or a toxic effect of the peptide at high concentrations remains to be determined. In most other areas studied, the excitatory effect of NT was most commonly observed. In many areas, this excitatory effect was apparently a direct postsynaptic effect of NT. However, different mechanisms may be involved (see Table 1). For example, in some areas NT acted through a decrease in membrane conductance, while in others no change or an increase in the membrane conductance was observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1463270 TI - Cooperative regulation of neurotensin/neuromedin N gene expression in PC12 cells involves AP-1 transcription factors. PMID- 1463271 TI - Control of anterior pituitary hormone secretion by neurotensin. AB - Neurotensin is localized in discrete populations of neuronal cell bodies with terminals in the hypothalamus and median eminence. High-affinity binding sites for neurotensin have been demonstrated not only in the hypothalamus but also in the pituitary gland. These studies suggest a role for neurotensin in control of hypothalamic-pituitary function. We initially demonstrated that neurotensin could block the release of prolactin in conscious, ovariectomized and male rats after its injection into the third ventricle, whereas intravenous injection of the peptide significantly elevated plasma prolactin and increased prolactin release by pituitaries incubated in vitro. These results suggested that neurotensin had opposite actions on prolactin release, an inhibitory effect at a hypothalamic site and an excitatory one at the pituitary. Further studies employing dopamine receptor blockers and inhibitors of catecholamine synthesis indicated that the action of the peptide to block prolactin release was probably mediated by release of dopamine, which then inhibited prolactin release by the pituitary gland directly. We have evaluated the physiological significance of the peptide in control of prolactin release by intraventricular injection of highly specific antiserum against neurotensin. The antiserum evoked dose-related elevations in plasma prolactin in intact males that were significant but smaller in magnitude than those seen in females, actions opposite to those of the peptide itself, which indicates that the inhibitory action of the peptide within the brain is physiologically significant. Intravenous injection of this antiserum produced a significant suppression of plasma prolactin in females but not males, which indicates that the previously demonstrated stimulatory effect of the peptide on prolactin release by the gland is also physiologically significant because immunoneutralization of the peptide resulted in a decline in plasma prolactin. Our earlier experiments revealed that neurotensin had a dose-related ability to inhibit LH release in ovariectomized and ovariectomized, estrogen progesterone treated rats. Since it had no effect on the release of LH in vitro, we assigned a hypothalamic site for this action. It appears that this inhibitory effect of the peptide to suppress LH release is also physiologically significant since the intraventricular injection of the antiserum against the peptide produced a dose related stimulation of LH release in ovariectomized and ovariectomized, estrogen progesterone-blocked rats. The mechanism by which endogenous neurotensin inhibits the release of LHRH has yet to be evaluated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1463272 TI - The manifold actions of neurotensin, a trophotropic agent. PMID- 1463273 TI - Biosynthesis, maturation, release, and degradation of neurotensin and neuromedin N. PMID- 1463274 TI - Increased plasma levels of leukotrienes in response to neurotensin. PMID- 1463275 TI - Retrograde axonal transport of neurotensin in rat dopaminergic neurons. PMID- 1463276 TI - Autoradiographic localization of retrogradely transported neurotensin in nigrostriatal neurons. PMID- 1463277 TI - Neurotensin and neuromedin N undergo distinct proteolytic inactivation in ventral tegmental area and nucleus accumbens. PMID- 1463278 TI - Histamine-releasing peptide is formed from albumin by stimulated rat mast cells. PMID- 1463279 TI - Enhancement of mesolimbic rewarding brain stimulation by neurotensin injected into the accumbens, the subiculum, or the ventral tegmental area. PMID- 1463281 TI - Expression of neurotensin messenger RNA in a human pancreatic carcinoid tumor. PMID- 1463280 TI - Neurotensin mRNA expression in response to haloperidol is decreased in the dorsolateral striatum of aged rats. PMID- 1463282 TI - Cocaine effects on central nervous system neurotensin concentrations. PMID- 1463283 TI - MK-801 blocks the changes in neurotensin concentrations induced by methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, and GBR 12909. PMID- 1463284 TI - Internalization of neurotensin in cultured neurons. PMID- 1463285 TI - Mechanisms of neurotensin effects on pancreatic and duodenal bicarbonate secretion in the rat. PMID- 1463286 TI - Distribution of prepro-neurotensin/neuromedin N mRNA in the young and adult rat forebrain. PMID- 1463287 TI - Immunohistochemical detection of pro-neurotensin/neuromedin N processing intermediates in rat brain. PMID- 1463288 TI - Dopamine-neurotensin interactions in mesocortical neurons. Evidence from microdialysis studies. PMID- 1463289 TI - Neurotensin gene expression in the rat preoptic area. Implications for the regulation of reproduction. PMID- 1463290 TI - Antibodies against a 30 kilodalton cochlear protein and type II and IX collagens in the serum of patients with inner ear diseases. AB - Collagen molecules are major extracellular matrix proteins involved in the development and support of delicate auditory sensory organs. Type II collagen is widely distributed within inner ear tissues, while type IX is found only within the labyrinthine membrane and dense fibers of the tectorial membrane. Antibody specific for type II collagen has been shown to be elevated in some patients with hearing loss due to several presumably autoimmune illnesses (including Meniere's disease, otosclerosis, chronic progressive sensorineural hearing loss, and relapsing polychondritis). Purified human type II and IX collagens and an extract of human cochlear tissue were subjected to isolation by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose. The sera of 21 patients with inner ear disease were examined for the presence of anticollagen and anticochlear antibodies; the sera were used to probe Western blots of purified human collagens II, IX, and XI, and cochlear protein extract with peroxidase-conjugated goat anti human polyvalent immunoglobulin as the second antibody. Anti-type II collagen antibodies were seen in 12 of 21 (57%) patients, while 13 of 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was 21 (62%) had anti-type IX antibodies detectable by Western blot. A previously unreported 30 kd (probably noncollagen) protein was found by SDS-PAGE of human cochlear tissue extracts, with 3 patients, all with Meniere's disease, having antibody activity to this protein detected by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463291 TI - Spontaneous remission in experimental autoimmune labyrinthitis. AB - We investigated the time course of hearing impairment and cellular infiltration into the inner ear after systemic sensitization of guinea pigs with a single intradermal injection of bovine inner ear antigen (IEAg) in complete Freund's adjuvant (CFA). Lymphocytes and polymorphonucleocytes appeared mainly in the scala tympani on days 7 to 14, and in addition there was thickening and cellular infiltration of the round window membrane at day 14. These cellular infiltrations resolved after day 28. The auditory brain stem response thresholds from IEAg sensitized animals were significantly elevated after day 7. Some sensitized animals (n = 5) had spontaneous remissions after day 28; however, the hearing thresholds did not completely recover. These results demonstrate that experimental autoimmune labyrinthitis can be induced by a single inoculation of IEAg-CFA and that remission, as evidenced by clearing of the cochlear cellular infiltration and improved hearing thresholds, can occur spontaneously. PMID- 1463292 TI - Massive osteolysis (Gorham's disease) of the temporomandibular joint. PMID- 1463293 TI - Cystic squamous cell carcinoma metastatic to the neck from occult primary. PMID- 1463294 TI - Nonsquamous carcinomas of the larynx. AB - Nonsquamous carcinomas make up fewer than 1% of all epithelial malignancies of the larynx. The majority are subsurface in origin and arise from seromucous glands of the larynx. Adenoid cystic carcinoma is not only representative of this group, it is the most prevalent. All other salivary-type carcinomas are rare. Rarer still are surface adenocarcinomas. Neuroendocrine carcinomas appear to constitute the majority of so-called laryngeal adenocarcinomas. PMID- 1463295 TI - Indium 111-labeled leukocyte scintigraphy in evaluating head and neck infections. AB - This retrospective study looked at the role of indium 111-labeled white blood cell (111In WBC) scintigraphy in head and neck infections. The efficacy of 111In WBCs was compared to gallium 67 citrate (67Ga) and technetium Tc99m methylene diphosphonate (99mTc MDP) scintigraphy in detecting and monitoring the resolution of infection. For 22 active infections, the sensitivities for 111In WBC, 67Ga, and 99mTc MDP scintigraphy were 94%, 56%, and 86%, respectively, and the specificities for 111In WBC, 67Ga, and 99mTc MDP scintigraphy were 100%, 43%, and 0%, respectively. For 8 successfully treated infections, all seven 111In WBC studies became negative after therapy, in as short an interval as 1 month. In contrast, all seven 99mTc MDP images remained positive for as long as 6 months after therapy. The seven 67Ga studies had variable results, with four (57%) remaining positive, including two (28%) positive at 6 months after therapy. These results suggest that 111In WBC scintigraphy should be the initial radionuclide imaging tool in detecting active head and neck infections because of its greater accuracy, and its ability to revert to normal much sooner than 67Ga or 99mTc MDP scintigraphs when applied to a subset of patients with resolved infections. PMID- 1463296 TI - Combined effects of noise and cisplatin: short- and long-term follow-up. AB - The combined effects of noise exposure and intravenous cisplatin injection on electrophysiologic hearing thresholds in guinea pigs were studied with short-term and long-term follow-up. The combined effects on the permanent threshold shift were dependent on the order of exposure. A potentiation was achieved when noise exposure preceded cisplatin injection by 30 minutes or by 3 days. Cisplatin injection 2 or 3 days before noise exposure produced no significant potentiation or inhibition. The combined effects on the temporary threshold shift were not influenced by the sequence of exposure. PMID- 1463297 TI - Maxillary sinus atelectasis. AB - Two patients are presented with maxillary bone loss and atelectasis of the sinus walls in association with chronic subclinical maxillary sinusitis. Maxillary sinus atelectasis results in a mild cosmetic deformity, but may also cause diplopia by involving the orbital floor. Ostial obstruction and inflammation mediated osteopenia are postulated to be the responsible mechanisms. Surgical treatment of the sinusitis may prevent progression of the bone loss. PMID- 1463298 TI - Ultrastructural changes in human nasal cilia caused by the common cold and recovery of ciliated epithelium. AB - Changes in the ultrastructure of human respiratory cilia caused by the common cold were studied in 12 patients. The nasal mucosa was studied three times: on the first or second day after the beginning of symptoms, and 1 week and 3 weeks after the first biopsy. The damage was most severe at 1 week. The most remarkable finding was the loss of cilia and ciliated cells. However, the ultrastructure was usually normal, without any increase in tubular anomalies, as compared with the normal material of the previous reports. Three weeks after the beginning of the disease the number of cilia and ciliated cells had increased to nearly normal. However, as a sign of regeneration, immature short cilia (0.7 to 2.5 microns in length) were often seen. The ciliary orientation was uniform, dynein arms were normal, and there was no increase in the number of tubular anomalies. The results suggest that the impaired mucociliary function during viral infections is due to the loss of cilia and ciliated cells, rather than to ultrastructural anomalies in the cilia. The development of tubular anomalies and random ciliary orientation may require more extensive exposure to factors affecting ciliary function. PMID- 1463300 TI - Influence of general anesthesia on transiently evoked otoacoustic emissions in humans. AB - The influence of general anesthesia (GA) on transiently evoked otoacoustic emissions (TEOAEs) was studied in 19 normally hearing women undergoing surgery. Emissions were measured on the day before the operation, after premedication but before the beginning of the operation, and during and after the operation. There were no significant differences in TEOAE amplitude or in reproducibility between results obtained the day before the operation and after premedication. Ten patients received nitrous oxide (N2O) during GA (N2O group), and 9 patients did not (non-N2O group). The amplitude of TEOAEs was reduced during GA in 9 of 10 patients in the N2O group and in 7 of 9 patients in the non-N2O group. However, the average decrease of amplitude after the first 10 minutes was greater in the N2O group (4 +/- 3.4 dB) than in the non-N2O group (0.18 +/- 1.4 dB). The corresponding mean reproducibility of the response decreased in 9 of 10 patients of the N2O group (29% +/- 24%) and was nearly unchanged in the non-N2O group (2.3% +/- 7.2%). The time course of the amplitude reduction was similar in both groups. The smallest amplitudes were reached on an average by 19.3 +/- 11.4 minutes in the N2O group and by 17 +/- 13.6 minutes in the non-N2O group. Preoperative and postoperative TEOAEs were comparable in level and reproducibility. Differential frequency effects imply a middle ear effect for the greater reduction of TEOAE amplitudes in the N2O group due to gas diffusion into the middle ear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463299 TI - Diameter of the cochlear nerve in deaf humans: implications for cochlear implantation. AB - Although the parameters that are most important for postoperative speech perception in cochlear implantation have not been identified, it is assumed that the numbers of remaining cochlear neurons and spiral ganglion cells in the implanted deaf ears are critical. In this study, we evaluated the correlation of the maximum diameter of the cochlear and vestibular nerve trunks with the number of spiral ganglion cells in horizontal sections of the temporal bone of 42 patients who were profoundly deaf during life, and in 5 patients with normal hearing. The maximum diameters of the cochlear, vestibular, and eighth cranial nerves were significantly smaller in the deaf population as compared to normal hearing controls. In addition, the counts of the remaining spiral ganglion cells were significantly correlated with the maximum diameter of the cochlear (p = .0006), vestibular (p = .001), and eighth cranial nerves (p = .0003). The regression equation estimated that 25% of the variance of the spiral ganglion cell count was predicted by the maximum diameter of the eighth nerve. Although the results of this study suggest that preoperative radiographic imaging of the diameter of the eighth nerve may be helpful in predicting the residual spiral ganglion cell count, the wide variability of diameters of the eighth nerve in hearing and deaf subjects militates against this theoretic usefulness. PMID- 1463301 TI - [Insulin therapy using a portable pump in children. Apropos of a pediatric experience]. AB - Experience accumulated with 17 pediatric patients with insulin-dependent diabetes mellitus treated with an insulin pump is reported. Follow-up exceeds four years in seven patients. A significant improvement in metabolic control was seen in only four patients and was confined to the first year of use of the pump. Overall, the improvement in control was not significant. Severe hypoglycemia was uncommon (0.27/patient-year). Ketoacidosis was rare (0.08/patient-year). Transient ketosis was the most common adverse event and was often related to technical problems which should immediately lead to appropriate action by patients who have received proper education. Use of an insulin pump remains an alternative which deserves to be considered when conventional therapies fail. PMID- 1463302 TI - [Idiopathic pericerebral swelling (external hydrocephalus) of infants]. AB - Benign enlargement of the subarachnoid spaces was diagnosed in 41 infants on the basis of ultrasound and/or CT scan findings. 10 MHz transfontanellar ultrasonography is without doubt the most reliable investigation in this condition (skull-to-cortex distance greater than 5 mm). Patients with extracerebral collections due to a clearly identifiable pathologic process (e.g., prematurity, IUGR, neonatal distress, malnutrition) were excluded from the study. Macrocrania developed rapidly in 72% of patients, either as the single manifestation (30%) or with delayed motor development and hypotonia (30%). Other clinical patterns included evidence of intracranial hypertension (15%) and hypotonia without macrocrania (20%). The two main findings of this study were the high rate of familial forms and the severity of early hemorrhagic complications, i.e., spontaneous subdural hematoma (5/41 cases), with permanent neurologic impairment in some instances (2/5 cases). These complications call into question the benignity of this syndrome whose long-term outcome, particularly in terms of cognitive function, is as yet unknown. PMID- 1463303 TI - [Peptic esophagitis and scoliosis in children]. AB - Four pediatric cases of peptic esophagitis in patients with severe dorsolumbar scoliosis including three with a history of neurological disease provide the opportunity to point out that curvature of the spine fairly often causes development of gastroesophageal reflux. By displacing the anchoring points of the stomach and stretching the lower esophageal sphincter, scoliosis can be responsible for malposition of the cardia and fundus and for gastroesophageal reflux. Furthermore, plaster corsets increase intraabdominal pressure and may therefore promote gastroesophageal reflux. PMID- 1463304 TI - [Donath-Landsteiner hemolytic anemia. Physiopathological, diagnostic and therapeutic aspects]. AB - Donath-Landsteiner hemolytic anemia accounts for one third of all immunologic hemolytic syndromes in pediatric patients. Diagnosis is suggested by results of the direct Coombs test which is positive with anti-C3d, evidence of erythrophagocytosis on admission blood smears, and results of the Donath Landsteiner test. Anti-P specificity should be routinely looked for. Management, required once the diagnosis is established, is symptomatic. Warmed red blood cell concentrates should be used for blood transfusions. Exposure to cold should be avoided. Use of maintenance corticosteroid therapy is no longer acceptable. PMID- 1463305 TI - [Cantrell syndrome or the "shagreen skin" pentalogy. Apropos of 3 cases]. AB - Three patients with incomplete forms of Cantrell syndrome underwent surgical therapy at the Department of Infantile Surgery in Strasbourg, France, between 1979 and 1990. One patient had a giant omphalocele. Another had a ventricular septal defect. Two of the three patients are alive and doing well. The nosology and prognostic factors in Cantrell syndrome are discussed. PMID- 1463306 TI - [Neonatal streptococcus group B infection in Yaounde (Cameroon). Epidemiologic and clinical aspects]. AB - This study was designed to investigate epidemiologic and clinical features of neonatal group B streptococcal infections. Sixty cases seen over a 60-month period were reviewed. Incidence was 0.8% of admissions. Most affected infants were from low-income families (86.7% of mothers were unemployed and 73.5% of homes were without running water). Neonatal infection was delayed in most instances (76.67%). Fetid vaginal discharge (60%) and premature rupture of the membranes (35%) were the main findings upon history taking. Abnormal body temperature regulation (76.7%) was the most prominent clinical manifestation. Respiratory distress developed in 25% of patients. Meningeal involvement occurred in 73.3% of patients. Serotype B III was recovered in 31 of the 34 cases (91%) in which serotype was determined. Mortality rate was 21.7% and permanent sequelae occurred in 8.3% of patients. PMID- 1463307 TI - [Parent-pediatrician synergism faced with childhood fever]. PMID- 1463308 TI - Griseofulvin in the treatment of oral lichen planus: adverse drug reactions, but little beneficial effect. AB - An open trial was conducted of systemic griseofulvin in the treatment of oral lichen planus. Eleven patients completed the trial. Symptomatic benefit was noted in 21% of the twenty-three patients starting the trial, but there was no clinical improvement, and about one half of the group starting the trial suffered adverse drug reactions. PMID- 1463309 TI - Central odontogenic fibroma: a case report. PMID- 1463310 TI - Recurrent aphthous stomatitis: the efficacy of replacement therapy in patients with underlying hematinic deficiencies. AB - A group of thirty-four patients with recurrent aphthous stomatitis (RAS) and single hematinic deficiencies were given replacement therapy after any reason for the deficiency had been sought and excluded. The response of the RAS was assessed in an open trial. The aphthae in 70% of patients subjectively improved with hematinic replacement therapy, a benefit exceeding the defined placebo response in recurrent aphthous stomatitis. PMID- 1463311 TI - Radiographic study of mandibular nutrient canals. AB - This study was undertaken to determine the correlation between the presence of nutrient canals in the mandibular anterior region and sex, age, edentulous mandible, periodontal disease, and high blood pressure. The periapical roentgenograms taken from the mandibular anterior region of 1040 patients were examined. According to the data obtained from the present study, the occurrence of nutrient canals in the mandibular anterior region seemed related to age, edentulous mandible, periodontal problems, and high blood pressure. However, no relation to sex was found. PMID- 1463312 TI - Effects of restorations and carious lesions on the periodontium in humans. AB - The objectives of the present study were to examine the effects of dental restorations, crowns and fillings, and carious lesions on the periodontal tissues. One hundred and one clinic patients were selected on the basis of each having one or more teeth with either carious lesions or restorations, and having contralateral teeth without restorations or carious lesions. Debris, calculus, gingivitis, pocket depths, and bone loss were evaluated using objective criteria of assessment for each condition. The results showed significantly greater gingivitis, pocket depth, and bone loss around teeth with restorations and carious lesions than around their controls. PMID- 1463313 TI - Herniation of an antral polyp through an oroantral fistula. AB - This paper reports a case of herniation of an antral polyp through an oroantral fistula, appearing as a polypoid lesion of the alveolar ridge. The patient was a 24-year-old female, and her upper molar had been extracted two months previously. The lesion was asymptomatic, and was a soft tissue mass, red in color and nontender to palpation, involving the alveolar ridge in the maxillary molar area. Review of the literature yielded only a few other such cases. PMID- 1463314 TI - Dental disease in the differential diagnosis of fever of unknown origin. AB - A patient with a one-year history of fever of unknown origin is presented. Extensive work-up failed to reveal the source of the fever. Treatment of periodontal infection resulted in complete cure, suggesting a cause-effect relationship. A possible role of Interleukin 1 (IL-1), universal pyrogen, in periodontal disease is suggested. PMID- 1463315 TI - Ehlers-Danlos syndrome: a case report. AB - A 13-year-old male patient classified as Type VIII, Ehlers-Danlos syndrome, in which the typical periodontal findings are not seen, is presented. The patient has many partially erupted deciduous teeth and partially erupted mandibular permanent incisors. It is suggested that Type VIII has two subdivisions. In subdivision A there is periodontal involvement with a normal eruption pattern; subdivision B has no periodontal involvement, but the teeth do not erupt. PMID- 1463316 TI - [The metastatic liver: a rare cause of hepatocellular insufficiency]. AB - Liver metastases are frequent, often large and sometimes very late in skin or choroid metastatic melanoma. Hepatic failure is a rarely described complication in metastatic liver melanoma. We report a case of liver failure in a metastatic liver melanoma in a woman 76 years old, treated 16 years before for a choroid melanoma. About this case, we discuss the frequency, the location of primitive tumors and mechanism of liver failure in metastatic liver. PMID- 1463317 TI - [A new case of collagenous colitis associated with rheumatoid polyarthritis]. AB - The authors describe a case with concomittant chronic polyarthritis and collagenous colitis. The sub-epithelial band-like collagenous deposit may be the result of fibroblastic production with autoimmune stimulation. PMID- 1463318 TI - [Management of a focal hepatic mass: propositions of a workshop]. AB - Focal hepatic masses are a common problem, due to the expansion of ultrasound. Individuals engaged in the four disciplines involved (hepatogastroenterology, digestive surgery, radiology and pathology) met to summarize the information available, to compare their experience and to make synthetic proposals. The method consisted of an expert report, discussion of the clinical cases, workshop discussion for each discipline around synthetic proposals, reporting of these proposals in full session and discussion. The results, i.e. the synthetic and consensual proposals concerned diagnosis, treatment and monitoring of focal hepatic masses are presented for each discipline. PMID- 1463319 TI - [Description of a new disease: pancreatic lithiasis with radiolucent calculi]. AB - 118 patients presenting with pancreatic lithiasis were consecutively observed in our service. They underwent both an endoscopic pancreatography and god plain films of the abdomen. Calculi were classified in 3 groups: 1) Radiolucent calculi (17 cases, 5 females; 4 hereditary cases) are build up of amorphous residues of lithostathine S. They are not related to either alcohol, diet or tobacco. 2) Target calculi (27 cases, 4 females; 3 hereditary cases) have a radiolucent core as in 1 and a peripheral calcification. They are a late evolutionary stage of radiolucent lithiasis. The frequency of females and of hereditary cases is significantly greater in form 1 + 2 than in form 3. These two forms are a newly described disease without relationship with nutrition, alcohol or tobacco but the peripheral calcification of radiolucent calculi is favoured by alcohol and tobacco. This disease could be hereditary. 3) Calcic lithiasis (74 cases, 8 females, 2 hereditary cases) is the most frequent form of pancreatic lithiasis. Its cause is nutritional. PMID- 1463320 TI - [Antibiotic residues and digestive microflora]. AB - Can antibiotic residues modify the human gut flora, and select drug resistant bacteria? In volunteers given ampicillin (1.5 mg/d) or oxytetracyclin (2 mg/d), the fecal excretion of resistant enterobacteria was not changed significantly. However a possible effect would be hidden in human beings by the huge day to day fluctuations in the resistant bacterial populations. Heteroxenic mice (i.e. germfree mice associated with the flora of a human donor) and dixenic mice (i.e. mice harboring 2 isogenic strains, one of which carries an R-plasmid) are possible models to study the gut flora in vivo without contaminations and interfering factors. Minimum selecting doses in these models are between 0.5 and 10 mg antibiotic per liter of drinking water. These doses are smaller than what a consumer could ingest in food. Last, fecal resistant enterobacteria directly come from contamined food, as shown by their clearance from stools of volunteers eating a sterile diet. Hence antibiotic residues do not modify meaningfully the gut flora. PMID- 1463321 TI - Estrogen suppresses hepatitis B virus expression in male athymic mice transplanted with HBV transfected Hep G-2 cells. AB - Hormones are known to regulate both viral and cellular genes. It has been shown previously that estrogen has an effect on liver gene transcription and mRNA stability. Sex hormones might have a role in the chronic persistence of hepatitis B virus (HBV) infection. In fact, there is a male preponderance in the incidence of chronic HBV infection, and HBsAg expression was reported to be much higher in male transgenic mice than in the females. We investigated the effect of estrogen on HBV gene expression and regulation in athymic mice bearing 2.2.15 cells, a human hepatoblastoma cell line derived from Hep G-2 transfected with HBV sequences. Both male and female mice were treated with estradiol after tumors could be observed. Episomal DNA was extracted from the tumors and hybridized with 32P-labelled HBV DNA. Southern blot and slot blot analyses demonstrated that male mice had higher expression of HBV DNA. Estrogen treatment suppressed HBV DNA expression in males, but had only a minor effect on females. HBeAg production in male mice was also inhibited by estrogen treatment. HBV RNA extracted from 2.2.15 cells showed 2-3-fold reduction following beta-estradiol treatment. Moreover, inhibition of HBV transcription by estrogen was demonstrated by an RNA pulse labelling experiment. These data indicate that estrogen inhibits HBV expression in the in vivo model presented in this study. These results might contribute to a better understanding of the effect of sex hormones on the pathogenesis of HBV induced liver disease. PMID- 1463322 TI - The influence of dextran sulfate on influenza A virus fusion with erythrocyte membranes. AB - Dextran sulfate suppresses the low pH-induced fusion of influenza virus A/Brazil 11/78 with erythrocyte membranes, as shown by fluorescence dequenching assay, using the fluorophore octadecylrhodamine B chloride (R18). Inhibition of fusion was maximal at pH 5.0, while at higher pH values (> 5.6) fusion was not affected. Hemolysis of intact red blood cells by influenza A virus at low pH values is also prevented by dextran sulfate. The inhibiting effect of the polymer is mainly ascribed to repression of virus attachment. Evidence is given that the conformational change of the virus envelope protein hemagglutinin (HA) responsible for triggering fusion is not affected by the polymer. PMID- 1463323 TI - Antiviral effects of recombinant human tumor necrosis factor-alpha in combination with natural interferon-beta in mice infected with herpes simplex virus type 1. AB - The protective effects of combination therapy utilizing recombinant human TNF alpha (rTNF-alpha) and natural murine interferon-beta (IFN-beta) in mice infected with herpes simplex virus type 1 (HSV-1) was investigated. Mice treated with rTNF alpha alone at all of the doses tested (a single i.v. administration, 2.3-2,300 micrograms/kg; multiple i.p. administrations 0.4-250 micrograms/kg) as well as mice that received IFN-beta alone at doses of 16 x 10(4) U/kg or less resulted in a 0% survival rate. Combination therapy consisting of a single administration of rTNF-alpha (230 and 23 micrograms/kg) and multiple administrations of IFN-beta (4 x 10(4) U/kg) resulted in a 40% and 60% survival rate. Multiple treatments of infected mice with rTNF-alpha (50 and 10 micrograms/kg) in combination with IFN beta (4 x 10(4) U/kg) resulted in 50% and 70% survival rates, respectively. These results suggest that the combination therapy of rTNF and natural murine IFN-beta produce synergistic protective effects in mice infected with a lethal amount of HSV-1. PMID- 1463324 TI - Project team investigates how the Association's organizational structure can be improved to meet future changes, challenges. AB - The members of the Project Team realize that this is a very different concept than that to which members are accustomed. The details of such a change would be developed with member input, and the new structure would be phased in over a period of several years to be fully implemented by the year 2000. PMID- 1463325 TI - The greening of the OR. Reduce, reuse, recycle. PMID- 1463326 TI - Laparoscopic colotomy, polypectomy. Innovative minimally invasive procedure. PMID- 1463327 TI - Breaking the time barrier. Learning from a new product evaluation. PMID- 1463328 TI - Award for Excellence in Perioperative Nursing--AORN's ultimate prize. AB - Excellence should be part of our daily practice. Through sharing of knowledge, ideas, and information, private excellence is transformed into public excellence and deserves recognition. AORN recognizes that many individuals have and do make a difference in their individual practice settings as well as by their national influence. The importance of recognizing members for their contributions to perioperative nursing is evidenced by the addition of the two new awards and the many other individual awards given by the Association. The importance of peer recognition and participation in the selection process for the awards cannot be underestimated. The Award for Excellence Committee encourages your continued involvement in the nomination process. Excellence is not just for a chosen few! It is something each of us is capable of doing each day. What we need to do now is to recognize it in ourselves and others and to accord those who display this quality the recognition they deserve. PMID- 1463329 TI - Recommended practices. Sanitation in the surgical practice setting. PMID- 1463330 TI - Recommended practices. Selection and use of packaging systems. PMID- 1463331 TI - Clinical issues: risks of donor organs; tuberculosis in the OR; unexplained immunodeficiency states; the HIV-infected health care worker. PMID- 1463332 TI - Ownership rights to tissue specimens. PMID- 1463333 TI - [Current status of research on cancer metastasis]. AB - Metastasis is the most critical problem for the oncologists to treat cancer patients. The processes of cancer invasion and metastasis consist of a long series of sequential, interrelated, and complicated steps. Understanding the mechanisms responsible for cancer invasion and metastasis is, therefore, a primary goal of cancer research and will produce new approaches to control and inhibit cancer metastasis. Massive investigations are being carried out for cancer metastasis. Recently many investigations on the research fields other than cancer result in being related with metastasis research. We reviewed the current findings, including our data, on the research for cancer metastasis and discussed the current status of the research. PMID- 1463334 TI - [Epidemiology of pancreatic cancer]. AB - Pancreatic cancer has been increasing in recent years in Japan. The number of pancreatic cancer deaths in 1990 was 13,318, accounting for 6.1% of all cancer deaths in Japan. The increasing trend of pancreatic cancer mortality is observed more markedly in the elderly population over 60 years of age, and especially in persons over 80. Possible reasons for the increase of pancreatic cancer were discussed. The geographic distributions of pancreatic cancer mortality in Japan and around the world indicate that the mortality is higher in northern Japan and even higher as the latitude increases. Some possible reasons for the inverse relationship between the pancreatic cancer mortality and the latitude were discussed. From epidemiological studies several risk factors for pancreatic cancer were reported; smoking, drinking, excess intake of meat and cholesterol, coffee, radiation, cholecystectomy, etc. However, more epidemiological studies are needed to identify and confirm risk factors for pancreatic cancer and to promote primary prevention of pancreatic cancer. PMID- 1463335 TI - [Treatment and present status of pancreatic cancer]. AB - The Pancreatic Cancer Registry of the Japan Pancreas Society registered 11,317 patients of pancreatic cancer during these ten years. Among these patients, resectional procedures were performed on only 3,743 cases (33.1%). The actual 5 year survival rate of the patients who underwent resection was 16.6%. As for small cancer which was less than 2cm, the 5-year survival rate was 41.0%. In pancreatic cancer local recurrence was more frequent than other cancers of pancreatic head lesions. Extended operation which means lymphangiectomy more than R2 has not improved survival rate generally But some patients who underwent extended operation have survived long period. Multi-disciplinary treatment of pancreatic cancer has been tried. PMID- 1463336 TI - [Selection of methods for diagnosis and treatment of pancreatic cancer]. AB - The prognosis for ductal cancer of the pancreas is extremely poor. Diagnosis of pancreatic cancer in the earlier stages has become possible by taking note of early symptoms, mild abdominal pain, back pain, anorexia, diabetes and obstructive jaundice. Presently, measurements of amylase in serum and urine, serum elastase-1, serum CA 19-9 and US are usually used for screening patients with the symptoms. Furthermore, for correct diagnosis, intensive study by US, dynamic CT, ERCP, MRI, cytological examination and CEA of pancreatic juice, endoscopic pancreatoscopy and endoscopic ultrasonography are used. The results of surgical treatment for resectable pancreatic cancer are not generally favorable. Extended pancreatic resection (pancreatoduodenectomy, total pancreatectomy or distal pancreatectomy) with en bloc dissection of the lymph nodes has been performed for patients with invasive cancer. However, local recurrence and distant metastasis usually occurred after surgery. It seems difficult to cure pancreatic cancer by surgery alone. To improve the prognosis of resectable pancreatic cancer, multimodality treatment with intraoperative radiation therapy and chemotherapy is performed and a better outcome is achieved. PMID- 1463337 TI - [Involvement of lymph nodes and neural plexus in carcinoma of the pancreas]. AB - We studied 428 lymph nodes attached to the head of the pancreas (13,14,17) in 18 patients with ductal carcinoma of the pancreatic head. These were classified into the small size of the lymph nodes less than 5mm (group S), the moderate size of the lymph nodes (group M) and the large size of the lymph nodes more than 10 mm (group L). The metastases were seen in 76 nodes, which consisted of 49 with group S, 14 with group M and 13 with group L. The lymph node involvement in group (14) S was found in 7 of 18 patients (38.9%), that in group (14) M was in 4 (22.2%) and that in group (14) L was in 2 (11.1%). In these involved cases, the primary tumors tended to be locate in the portion near the superior mesenteric artery, such as in the uncinate process. Invasion of extrapancreatic neural plexus was noted in 9 of 18 patients (50%). There was no significant correlation between nerve plexus invasion and lymphatic invasion by Spearman's rank correlation. In addition, any close relationship between plexus invasion and primary tumor location could not be indicated. These results suggested that neural invasion in pancreatic carcinoma is independent of lymphatic invasion, and the routes of cancer spread via the neural plexus are different from those via the lymphatic vessels. Those without liver metastases survived longer than those with liver metastases, which were characteristically multiple. PMID- 1463338 TI - [Extensive radical surgery for carcinomas of the head of the pancreas]. AB - Since 1973, we have applied extensive radical surgery for the head of the pancreas in order to improve not only the resection rate but also the surgical therapeutic results. The main points of our surgical procedure are as follows: (1) complete resection of surrounding connective tissues in retroperitoneum including extrapancreatic neural plexus. (2) extensive lymph node dissection, and (3) combined resection of the portal vein. As a result, our 3-year survival rate has increased to 31.4% and the 5-year survival rate to 27.9% in patients who underwent the macroscopically complete resection. These surgical therapeutic results are not satisfactory, but we have had 10 patients who survived more than 3 years. It is also true, however, that this procedure is extremely invasive and requires careful, long-term nutritional management after surgery. Therefore, the cooperation of not only the patients themselves but also their families is indispensable for the success of the treatment. PMID- 1463340 TI - [Radiation therapy of pancreatic cancer]. AB - We have been using external beam radiotherapy (EBRT) and intraoperative radiotherapy (IORT) for both resectable and unresectable pancreatic cancer patients. EBRT (50-60 Gy) was combined with IORT (25-33 Gy) whenever possible, but otherwise EBRT or IORT was given alone. In patients with unresectable tumor but no distant metastasis, the median survival time (MST) was 7.5 months (M) for the EBRT group and 9 M for the EBRT+IORT group. These MST's were significantly longer than the MST of 3 M of patients who had been treated without radiation (historical control). In non-Stage IV patients undergoing non-curative resection, the MST was 12.5 M for the EBRT group, 15.5 M for the EBRT+IORT group, and 7 M for the historical control. In patients undergoing macroscopic curative resection, the MST was 14 M for the EBRT group, 10 M for the EBRT+IORT group, and 10.5 M for the historical control. In Stage IV patients (with distant metastasis), the MST was 4.5 M for the EBRT group, 4 M for the EBRT+IORT group, 2 M for the IORT group, and 2.5 M for the historical control. Thus, radiotherapy appeared useful especially in non-Stage IV patients undergoing non-curative or no resection. A decrease or relief of pain was obtained in 90% of patients with unresectable lesions. Radiotherapy seems to play an important role in the treatment of pancreatic cancer but more aggressive combined treatment seems to be necessary to further improve the dismal prognosis of pancreatic cancer patients. PMID- 1463339 TI - [Chemotherapy for advanced pancreatic carcinoma]. AB - In advanced pancreatic cancer, chemotherapy has no curative potential, and the goal is to palliate symptoms or delay their onset so as to improve the quality of life of patients. There is no standard chemotherapeutic regimen with a clear advantage in survival prolongation or response rate, over any other regimen. Moreover, difficulties in determining the chemotherapeutic response have made accurate determination of the response rate virtually impossible for each trial. 5-FU and MMC are two main drugs so far in single-agent chemotherapy, but streptozotocin, doxorubicin, ifosfamide, epirubicin and CDDP are also investigated. FAM and SMF are the representative regimen of combination chemotherapy, but recently FP or biochemical modulation have been under close scruting. For greater improvement of chemotherapy, a new drug or combined modality approach is awaited. PMID- 1463341 TI - [Sensitivity test for anti-tumor agents-3. MTT assay and its clinical effect]. AB - MTT assay, a sensitivity test of anti-tumor agents was performed, and its clinical usefulness, was discussed. In 15 surgical specimens, the cell suspensions were prepared aseptically, and divided into three processing; namely, Papanicolaou (Pap) smears to confirm the malignant cells, MTT assay, and cell cultures in chamber slides. MTT assay was evaluated only when tumor cells in the chamber slide were observed 50% or more by Pap staining. Drugs judged to be effective were applied for patients, resulting in 64.2% of predictive accuracy in the sensitivity. Conclusions; 1) MTT assay was developed for sensitivity test of anti-tumor agents, 2) Strict assessment was carried out by the confirmation of cancer cells using chamber slides, 3) On clinical usefulness, predictability for the sensitivity was 64.2%, that for resistance was 100%, and over all predictability was 66.7% 4) MTT assay was useful for the determination of effective and for elimination of ineffective drugs. PMID- 1463342 TI - [Pharmacokinetics of carboplatin after intraperitoneal administration and clinical effect in ovarian cancer]. AB - The patients with ovarian cancer are apt to combine peritonitis carcinomatosa (PC). The effect of intraperitoneal (IP) administration of CDDP against peritonitis carcinomatosa was examined. Hydration was not necessary when CBDCA was injected, because nephrotoxicity of CBDCA was very low compared to CDDP. We studied pharmacokinetics of IP-CBCCA and its efficacy and safety. Four hundreds and fifty mg of CBDCA was dissolved in 1,000 ml of saline and administrated through the subcutaneously implanted Infuse-A-Port for 60 minutes. Complete response was 25%. The platinum concentration in the ascites (injected saline) decreased to 90.8 micrograms/ml at 2 hr after administration and to 3.8 micrograms/ml at 24 hrs, and 79.7 97.5% existed as free Pt. The concentration of serous Pt reached to 6.2 micrograms/ml at 15 min. and was kept at 6-8 micrograms/ml. and 52.4-92.7% existed as free Pt in serum. Pt was excreted to urine and reached to the peak concentration at 4 hr. Adverse effect was mainly myelotoxicity without renal toxicity and emesis. Leukocytopenia of grade 4 was 14.3%, thrombocytopenia was 25.0%. We tried IP administration to the outpatients. The doses were mainly 300 mg, but in some cases, it was escalated to 450 mg, Adverse effect of 300 mg was thrombocytopenia of grade 4 (4.8%). These results suggest that IP administration of CBDCA seemed to be a new method as locosystemic chemotherapy. We demonstrated new chemotherapeutic method to outpatients. PMID- 1463343 TI - [Phase I study of NK 622 (toremifene citrate)]. AB - A phase I study of NK 622 (toremifene citrate), a novel antiestrogen, was conducted in female patients with cancer. Patients received a single oral dosing or daily once oral dosing for five consecutive days. Any adverse effects were not experienced in the single dosing of 40 or 60 mg of NK 622. In the daily administration of 10, 20, 40, 60, 120, 240 and 480 mg/day, one of three patients who received 20 mg/day experienced grade 1 anorexia, three of four patients received 240 mg/day experienced adverse effects: Grade 1 leukopenia in one patient, Grade 1 general hot flush in one patient, and Grade 1 nausea, hot flush in the face and vertigo, Grade 2 anorexia, fatigue, dull headache and general hot flush in another one patient. These symptoms recovered to normal levels after treatment. Serum hormone levels were examined in postmenopausal patients, and a significant increase of the sex hormone binding globulin level was observed in the patients received 120 and 240 mg/day doses. Serum levels of NK 622 determined as free base (TOR) reached the peak levels in 2 to 4 hours after administration on the 1st and 5th day in daily treatment, while a metabolite N demethyltoremifene (TOR-1) reached the peak level in 4 to 170 hours. Maximum serum levels and area under the concentration versus time curves of TOR and TOR-1 increased dose-dependently. These values also increased by repetition of the treatment. Half-lives of TOR and TOR-1 in serum ranged in 74.5 to 148.9 hours and 154.1 to 653.1 hours, respectively. From these results, it was concluded that safety and efficacy of NK 622 should be assessed by using 240 mg or less doses in clinical phase II studies where breast cancer patients received long term treatment with NK 622. PMID- 1463344 TI - [The pharmacokinetics of intraperitoneal (IP) carboplatin (CBDCA) and dose-up study of intravenous (IV) cyclophosphamide (CPM) in combination with IP CBCDA for advanced ovarian cancer patients]. AB - The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients. The maximum concentration of free platinum (F-Pt) in serum following IP CBDCA administration was approximately 1/3 that of F-Pt following IV CBDCA. F-Pt in serum remained more than 90% of total platinum following IP CBDCA until 12 hours after administration. The t1/2 of F-Pt in serum after IP CBDCA administration was two times longer when compared with t1/2 following IV CBDCA, showing the slow peritoneal clearance of CBDCA. The area under curve (AUC) following IP CBDCA was approximately 67% of AUC following IV CBDCA. Cumulative urinary secretion (CUS) of platinum following IP CBDCA was 37% of CUS after IV CBDCA. The maximum tolerable dose of IV CPM in combination with 400 mg/m2 IP CBDCA was 550-600 mg/m2. The dose limiting factor of this combination therapy was leukocytopenia. Thrombocytopenia was mild in this study. Combination of 400 mg/m2 IP CBDCA and 550-600 mg/m2 seemed to be a tolerable and repeatable therapy for most patients with advanced ovarian carcinoma. Since thrombocytopenia was mild and the pharmacokinetics showed the smaller AUC of free platinum in serum following IP CBDCA, a dose-up study for IP CBDCA should be considered. PMID- 1463345 TI - [Salvage therapy for recurrent or refractory non-Hodgkin's lymphoma with etoposide, methotrexate, vindesine and prednisolone (EMVP)]. AB - Seventeen patients with recurrent or refractory non-Hodgkin's lymphoma were treated with EMVP (Etoposide 75 mg/m2 i.v. d 1-5, Methotrexate 100mg/m2 i.v. d 1, Vindesine 3 mg/body i.v. d 1, Prednisolone 60 mg/m2 p.o. d 1-5), repeating every 3 weeks. Six complete responses (35%) and five partial responses (30%) were obtained with an overall response rate of 65%. The median duration of response was 26 months (range 8-49+months) for complete response (CR) and 4 months (range 2-6 months) for partial response (PR). The median duration of survival was 31 months for CR, 11 months for PR and 10 months for all patients, respectively. The major toxic effect was myelosuppression. Leukopenia less than 1,000/mm3 and thrombocytopenia less than 25,000/mm3 occurred in 5 and 3 patients, respectively. The other toxicities were alopecia, nausea and mucositis. However, these toxicities were well tolerated and clinically manageable. These results suggested that EMVP therapy was an effective regimen for patients with recurrent or refractory lymphoma. PMID- 1463346 TI - [A case of renal cell carcinoma with lung metastasis and local recurrence effectively treated with nephrectomy and UFT]. AB - A 74-year-old woman was admitted on July 18, 1989 for an abnormality on her chest roentgenogram. Right renal tumor with bilateral pulmonary metastasis was detected and right nephrectomy was performed. Because of the progression of pulmonary metastasis and the local recurrence after surgery, UFT was orally administered at a dose of 300 mg everyday since Dec. 12, 1989. The chest roentgenogram on Nov. 21, 1990 showed progression of lung lesions. But at the 20 th month after the beginning of chemotherapy, both lung lesions disappeared completely and local recurrence around the operative wound strikingly improved. This is a rare case of renal cell carcinoma with local recurrence and lung metastasis successfully treated with UFT. PMID- 1463347 TI - [A case of adenocarcinoma of lung cancer with multiple brain metastasis and lymphangitis carcinomatosa responding well to chemotherapy with carboplatin, etoposide and ifosfamide]. AB - A 75-year-old male who suffered from adenocarcinoma of lung cancer with multiple brain metastases, developed left hemiplegia. After diagnosis, he was treated with 4,000 cGy whole brain radiation, but soon after advanced lymphangitis carcinomatosa set in and his general condition deteriorated. He was administered carboplatin combination with etoposide and ifosfamide. Lymphangitis carcinomatosa disappeared, and the main tumor of lung and brain metastases were not growing. We recommended carboplatin for an old patient or one in poor condition, because it had less cytotoxicity and retained the same antitumor activity compared with cisplatin. PMID- 1463348 TI - [Case report of a successful stage reduction of gastric carcinoma preoperatively treated by combined chemotherapy of 5-FU(UFT) and cisplatin]. AB - A 52-year-old woman was diagnosed to have IIc+IIa-like advanced gastric carcinoma in the upper stomach by X-ray and endoscopic examination with biopsy. CT scan revealed swelling of the para-aortic lymph nodes which was taken to be evidence of metastases of the gastric carcinoma. The patient was considered to have surgically non-curative gastric carcinoma (Stage IV), and preoperative chemotherapy was initiated. The regimen consisted of CDDP 50 mg (day 1-2, drip), 5-FU 750 mg (day 2-7, drip) and UFT 400 mg (from day 8 to the day before operation, oral). About one month after initiating treatment, total gastrectomy with lymph node dissection was performed. Histopathological examination of the section of the primary tumor revealed that only a few cancer cell nests (poorly differentiated adenocarcinoma) remained in the muscle and subserosal layer. In all of the lymph nodes which were suspected to have metastases preoperatively, cancer cells completely degenerated into mucinous lakes or foam cell nests. No liver metastasis nor peritoneal dissemination was detected, and this case was judged to be stage II after chemotherapy. PMID- 1463349 TI - [A case of gastric carcinoma with peritonitis carcinomatosa responding remarkably to etoposide, adriamycin and cisplatin (EAP) therapy]. AB - The patient was a 62-year-old male who had Borrmann 4 type gastric cancer. He presented massive ascites due to peritonitis carcinomatosa and the cytology of ascites was class V. He was treated with 3 courses of EAP (etoposide, adriamycin, cisplatin) therapy. Computed tomography showed ascites nearly disappeared. Remarkable improvement was observed by barium meal study and endoscopic examination, and partial remission (PR) was achieved. As for toxicity bone marrow suppression, alopecia and elevation of BUN were observed. PMID- 1463350 TI - [Argyrophilic nucleolar organizer regions: predictable variable of extent of lymph node metastasis in breast cancer]. PMID- 1463351 TI - Current practices for the prevention and treatment of malaria in children and in pregnant women in the Brazzaville Region (Congo). AB - Current practices for the prevention and treatment of malaria in children and in pregnant women in the Brazzaville Region (Congo) were studied in 1989 and 1990. Information was obtained by interviewing a total of 1152 subjects. Overall, chemoprophylaxis was used less than was the systematic treatment of fever. Fever was treated before seeking medical advice in over 50% of the cases. Two-thirds of those interviewed reported that they slept under mosquito nets. Families with lower socio-economic standards were less likely to use chemoprophylaxis, to have antimalarials in the home, and to own mosquito nets; and they were more likely to prefer injections and to purchase drugs in the local markets. PMID- 1463352 TI - The in vitro and in vivo antimalarial activity of some Mannich bases derived from 4-(7'-trifluoromethyl-1',5'-naphthyridin-4'-ylamino)phenol, 2-(7'-trifluoromethyl quinolin-4'-ylamino)phenol, and 4'-chloro-5-(7''-trifluoromethylquinolin-4'' ylamino)biphenyl -2-ols. AB - A series of di-Mannich base derivatives (4 and 5) from 4-(7'-trifluoromethyl 1',5'-naphthyridin-4'-ylamino)phenol and 2-(7'-trifluoromethylquinolin-4' ylamino)phenol, respectively, and mono-Mannich base derivatives (6) from 4' chloro-5-(7''-trifluoromethylquinolin-4''- ylamino)biphenyl-2-ol were assayed for activity against the chloroquine-sensitive (FCQ-27) isolate of cultured Plasmodium falciparum using the inhibition of uptake of radiolabelled hypoxanthine. All seven di-Mannich base derivatives (5) revealed a higher activity than chloroquine, whereas the di-Mannich base derivatives (4) were slightly less active (with some derivatives more active and some less active than chloroquine). The mono-Mannich base derivatives (6) were less active than chloroquine. Comparative tests of selected compounds of (4 and 5) using a morphological assay revealed no significant differences in activity between the chloroquine-sensitive (FCQ-27) and chloroquine-resistant (K-1) isolates. Selected di-Mannich bases (4 and 5) and the mono-Mannich bases 5-7''-bromo (and 7 trifluoromethyl)-1'',5''-naphthyridin-4''-ylamino)-3-(t- butylaminomethyl)-4' chlorobiphenyl-2-ols (7, X = Br, CF3) markedly suppressed parasitaemia in Plasmodium vinckei vinckei infected mice when administered (i.p.) in a single dose of 200 mg kg-1. PMID- 1463353 TI - The isoenzyme characteristics of Trypanosoma evansi and Trypanosoma equiperdum isolated from domestic stocks in China. AB - Twelve stocks of Trypanosoma evansi and one of Trypanosoma equiperdum isolated from domestic animals in China were examined for 16 enzymes using cellulose acetate and thin-layer starch gel electrophoresis. Differences were seen between stocks in only two of the enzymes, MDH and ALAT. Three of the T. evansi stocks, isolated from buffalo, and the T. equiperdum stock had the unusual pattern MDH-3, while all the other Chinese stocks had the common MDH-1. Two other stocks of T. evansi and again the T. equiperdum, all from equines, showed a new pattern ALAT 14. Otherwise the Chinese stocks had the same enzyme profile as T. evansi from elsewhere. PMID- 1463354 TI - Effects of long-term in vitro cultivation on the virulence of cloned lines of Leishmania major promastigotes. AB - The virulences of several clones from a single Leishmania major strain were studied in BALB/c mice. Clones showed the same pattern of infectivity and virulence two months after cloning as the parental population. After prolonged in vitro culture, however, it was apparent that two types of virulent clones existed: although the level of virulence remained stable in some clones, in others, such as C-11, it progressively decreased, as in the parental population. The progressive loss in virulence in a continuously cultured mixed population was probably due to selection, as the initial mixture of a stable virulent clone and a stable avirulent clone eventually yielded a totally avirulent promastigote population. After cultivation for 12 months, neither clone C-11 nor the parental population produced lesions in inoculated mice but virulent parasites were recovered from the inguinal nodes of the mice, possibly as a result of selection in vivo for virulent parasites. PMID- 1463355 TI - Post kala-azar dermal leishmaniasis: a neglected aspect of kala-azar control programmes. AB - Post kala-azar dermal leishmaniasis (PKDL) was studied in relation to the kala azar epidemic in Bihar, India. Between 1970 and 1989, 530 individuals, 302 males and 228 females, were admitted to the hospital of Patna Medical College with PKDL, the number of cases steadily rising from two in 1970 to 59 in 1989. The age of the patients varied from four to 70 years, with 33% aged 11-20 years and 16% 0 10 years. The prevalence of kala-azar in India also increased in the same period, mostly as the result of an epidemic of the disease in Bihar. There were no cases of this disease admitted to Patna Medical College from 1958-1970, it having become rare in India in the 1950s, possibly as a result of the DDT sprayed during the National Malaria Eradication Programme. In the period 1977-1990, however, there were 301,076 cases of kala-azar reported in Bihar alone, with a mortality rate over 2% (compared with 31,074 cases and a mortality rate below 0.4% for the rest of India). It seems possible that, once DDT spraying stopped, the re establishment of large sandfly population and infection of these vectors, largely as a result of them feeding on cases of PKDL, provoked the resurgence of kala azar. The study emphasizes the need to search for cases of PKDL, even in young children, and to monitor and effectively treat them as part of kala-azar control programmes. All patients could be cured if treated with the right dosage for the right period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463356 TI - Cutaneous leishmaniasis in Kabul: observations on a 'prolonged epidemic'. AB - Cutaneous leishmaniasis cases in Kabul have increased steadily in number since the first report, in 1964. This increase is despite insecticide application in houses and intensive detection and treatment of cases. The age distribution of infection remains as it was in 1972, and approximates that of the Afghan population. There is no evidence of accumulating immunity in the population. Multiple lesions are infrequent, but commoner on older people, and tend to be located on the arms and legs rather than the head. A house-to-house survey failed to distinguish risk factors promoting infection. Clustering of lesions on individuals and in households is interpreted as being due to multiple bites from a single infected sandfly. Phlebotomus sergenti numbers were strongly correlated with rainfall in the previous winter, but not with numbers of cases or numbers of houses sprayed. It is suggested that Leishmania tropica is at the limit of its range in Kabul and only remains endemic because of the rapid turnover of people in the City. PMID- 1463357 TI - Prevalence of Entamoeba histolytica and other intestinal parasites in a community from Maracaibo, Venezuela. AB - The prevalences of Entamoeba histolytica and other intestinal parasites were assessed in a suburban community of Maracaibo, Venezuela, by examination of a stool specimen from each of 342 individuals, using iron-haematoxylin stained faecal smears and formalin-ether concentration. The overall parasitic infection rate was 80.4%, and 65.8% of the population had multiple infections. The overall amoebic infection rate, which was highest in female adults, averaged 39.7%. The E. histolytica infection rate was 8.7% and most of those infected were passing cysts. Entamoeba polecki was observed in two samples. Amongst the protozoa, Entamoeba coli was observed most frequently (24.8%) and Giardia lamblia was the predominant pathogen (13.0%). Trichuris trichiura (71.9%) and Ascaris lumbricoides (54%) were the most common parasites, particularly in school children. The high rates of parasitic and multiple infections reflect the low socio-economic status of the community studied. PMID- 1463358 TI - Prevalence of human hydatid disease in northwestern Libya: a cross-sectional ultrasound study. AB - A total of 4103 people were screened in an ultrasound survey of the prevalence of hydatid disease (Echinococcus granulosus) in five areas of northwestern Libya; hydatid cysts were seen in 57 (1.4%), an overall prevalence of approximately 2.0% when adjusted for the likelihood of the occurrence of cysts in other sites in the body. All ultrasound-positive cases were confirmed by dot-blot ELISA. The prevalence of hydatid cysts increased with age, and differed between the sexes except in the five to 14 age group. All diagnosed cases, even those with large cysts, were asymptomatic. This study demonstrates the value of ultrasonography for screening field populations for hydatid disease. The technique was well received locally, facilitating the rapid collection of prevalence data from all ages and both sexes. Libyan people keep guard dogs, but there is little direct human:dog contact. Many people own a single dog, invariably kept outside and often chained up. Stray dogs are common, roaming the countryside to scavenge sheep carcases etc., and such dogs could be the main reservoir of E. granulosus in Libya. Because of the minimal direct human:dog contact, transmission of hydatid disease in Libya is probably indirect by ingestion of eggs from contaminated vegetables or drinking water. PMID- 1463359 TI - A survey of the intestinal helminths of refugees in Juba, Sudan. AB - A parasitological survey of refugees based in Juba, Sudan, involving 241 faecal samples, revealed that 66% of the population harboured intestinal helminths. The most commonly found infection was hookworm (36%), followed by Schistosoma mansoni (26%), Strongyloides stercoralis (20%), Hymenolepis nana (11%), Ascaris lumbricoides (1.2%), Trichuris trichiura (0.8%) and Taenia sp. (0.4%). Many of the specimens (42%) harboured a single infection, 21% had double, 2% triple and 1% quadruple infections. Parasite prevalences and intensities were analysed in relation to age, sex, religion and occupation: females (70%) were found to be more infected than males (64%); Muslims (50%) were less infected than Christians (68%) and agriculturalists (90%) were the most infected occupational group. PMID- 1463360 TI - Helminth parasites of carnivores in northern Iran. AB - A total of 100 jackals, 35 stray dogs, 13 cats, two badgers, one fox and one wild cat were collected from two provinces in northern Iran. On post mortem examination 41 species of helminths were recovered, at least 12 of which have been reported infecting humans in various countries. Hookworms were the most commonly found parasites, and Echinococcus granulosus showed the highest intensity of infection. Seven helminth species from jackals, three species from dogs, four species from cats and four species from badgers are reported for the first time in Iran. PMID- 1463361 TI - Diethylcarbamazine treatment of bancroftian and malayan filariasis with emphasis on side effects. AB - A total of 1015 filarial carriers were hospitalized and treated with DEC either in a long course with light doses (6, 7, 8, 9 or 10 mg kg-1 b.w. divided into three doses daily for seven days) or in a short course with heavy doses (15 mg kg 1 b.w. once daily for one, two or three days). The efficacy of the long course (85%) was much higher than that of the short course (59%); but the reaction rate following the heavy dose (87%) was higher than that following the light dose (72%). For Brugia malayi infections the overall efficacy was 92% and the reaction rate 82%, for mixed infections the respective rates were 85% and 77%, and for Wuchereria bancrofti infections 82% and 69%. The cure rates decreased from 93% in carriers with one to 10 microfilariae in 60 microns blood to 63% in those with over 100 Mff in 60 microns blood. Febrile reactions developed in 92% of carriers with mixed infections, in 91% of those with B. malayi, and in 84% of those with W. bancrofti. Overall, 63% of those treated were free of microfilariae on the last day of treatment, and 92% were free 48 months after treatment. PMID- 1463362 TI - Prevalence of dracunculiasis among Nigerian school children as an index of prevalence in their communities of origin. AB - A survey of dracunculiasis was carried out among pupils in their schools and among adults in the communities from which the pupils came, to determine whether the prevalence of infection in the pupils was a good index of the prevalence in their village. No significant difference was observed between the prevalence of current infection in pupils and that in their village of origin, although in some instances there were significant differences between the prevalence of previous infection in pupils and that in the corresponding village communities. The relevance and possible benefits of the rapid assessment of the prevalence of dracunculiasis obtained by a survey of school children are discussed. PMID- 1463363 TI - Distribution of hookworm infection in Cameroon. AB - Prevalence of hookworm infection was measured in Cameroon during a national survey carried out for a schistosomiasis research project. The survey provided a representative sample of the 10-19 year age group for each one of the 49 administrative divisions. Prevalences were low in the Extreme North province with a sahelian climate. Prevalences were high in the provinces with an equatorial climate except for the Centre province which is more developed. Regions with tropical Cameroonian climate, which receive a very heavy rainfall, showed the highest prevalences. Urbanized areas had lower infection rates than rural areas. It should not be assumed that hookworm prevalence is uniformly high throughout a tropical country. Since hookworm distribution shows wide variations, large control programmes should start with a thorough evaluation of the situation. PMID- 1463364 TI - A mark-release-recapture experiment with Anopheles lesteri paraliae in northwest Peninsular Malaysia. AB - In a coastal village in northwest Malaysia, 3231 fed Anopheles females of eight to 10 species were collected, marked with fluorescent dust, and released on three consecutive nights. In collections made on the 10 nights after the first release, 58 mosquitoes of three species, An. lesteri paraliae, An. subpictus and An. vagus, were recaptured; the recapture rates were 3.42%, 1.19% and 0.97%, respectively. The data for An. subpictus and An. vagus were insufficient for further analysis. Those for An. l. paraliae were plotted against time of recapture and, from the regression coefficient, an estimate of 0.68 was obtained for the daily survival rate. An independent estimate based on the parous rate during the previous year was 0.55. The temporal distribution of the recaptures strongly suggested a gonotrophic cycle and oviposition cycle of two days. PMID- 1463365 TI - The thigmotropic oviposition response of the sandfly Lutzomyia longipalpis (Diptera: Psychodidae) to crevices. AB - Two experiments were carried out to investigate if Lutzomyia longipalpis would be attracted and stimulated to lay eggs in crevices. In the first experiment, females were introduced into a chamber and offered the choice of oviposition in a test site consisting of artificial crevices, and an open control site. Significantly more eggs were laid in the crevices of the test site than in the control site. In the second experiment, females were individually isolated in vials containing vertically placed filter papers, either folded to provide artificial crevices or arranged to offer two flat surfaces. The females isolated with the folded papers laid significantly more eggs than those isolated with the flat papers. The post-oviposition survival rates of both groups of females were, however, similar. It is suggested that the oviposition preference of the fly for the surface crevices was due to thigmotropic behaviour. PMID- 1463366 TI - Reactivity of PHA-stimulated mononuclear cells from Schistosoma mansoni infected patients evaluated by blastogenesis and [3H]-inositol incorporation into inositolpolyphosphates. PMID- 1463367 TI - Videomicroscopy of intralymphatic-dwelling Brugia malayi. PMID- 1463368 TI - Evidence for a differential release of nitric oxide and vasoactive intestinal polypeptide by nonadrenergic noncholinergic nerves in the rat gastric fundus. AB - The roles of vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) in nonadrenergic noncholinergic (NANC) nerve-mediated relaxations were investigated in longitudinal muscle strips of the rat gastric fundus. Transmural stimulation (1-16 Hz for 2 min), VIP and noradrenaline evoked a prolonged relaxation of the rat gastric fundus, whereas NO evoked a transient relaxation. Only the electrically induced responses were blocked by tetrodotoxin. The inhibitor of NO biosynthesis NG-nitro-L-arginine (L-NNA) preferentially inhibited the relaxations induced by low frequency stimulation. In contrast, trypsin mainly reduced the electrically induced relaxations to high frequency stimulation; the NANC relaxations resistant to trypsin were further inhibited by L-NNA. VIP-induced relaxations were abolished by trypsin, but remained unaffected by L-NNA. NO- or noradrenaline-induced relaxations were not inhibited by either L-NNA or trypsin alone, whereas the combination of L-NNA and trypsin slightly reduced the noradrenaline-induced responses. These results suggest that NANC responses in the rat gastric fundus at low frequency are mediated mainly by NO, whereas at higher frequency NO together with a peptide, probably VIP, are released. PMID- 1463369 TI - Tolerance to the increase in coronary blood flow induced by KRN2391. AB - We examined whether KRN2391, isosorbide dinitrate and nitroglycerin induced tolerance in coronary arteries. Intracoronary arterial administration of KRN2391 (1 microgram), isosorbide dinitrate (30 micrograms) or nitroglycerin (3 micrograms) produced equipotent coronary vasodilatation. Development of tolerance was determined by whether the increase in coronary blood flow, caused by intracoronary arterial administration of these drugs, was attenuated by intravenous infusion of KRN2391, isosorbide dinitrate or nitroglycerin. The increase in coronary blood flow, caused by intracoronary arterial administration of KRN2391 was not affected by intravenous infusion of KRN2391 (0.3 or 1 micrograms/kg/min), isosorbide dinitrate (30 or 100 micrograms/kg/min) or nitroglycerin (1 or 3 micrograms/kg/min). The increase in coronary blood flow, caused by intracoronary arterial administration of isosorbide dinitrate or nitroglycerin, was significantly diminished by intravenous infusion of isosorbide dinitrate and nitroglycerin, but was unaffected by intravenous infusion of KRN2391. The present results suggest that KRN2391 does not induce acute tolerance by itself or cross-tolerance between KRN2391 and other nitrates. PMID- 1463370 TI - Comparative cardiovascular effects of KRN2391 and other coronary vasodilators in anesthetized open-chest dogs. AB - The effect of KRN2391 [N-cyano-N'-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulfonate] on the cardiovascular system and on myocardial oxygen consumption was compared with that of nicorandil and nifedipine in anesthetized dogs. Intravenous administration of KRN2391 (3-30 micrograms/kg) and nifedipine (1 and 3 micrograms/kg) decreased mean aortic blood pressure and total peripheral vascular resistance, and increased coronary blood flow, cardiac output and stroke volume. Heart rate was not significantly affected by KRN2391, but slightly increased by 1 microgram/kg of nifedipine. Nicorandil (100 and 300 micrograms/kg, intravenously) decreased mean aortic blood pressure, cardiac output, stroke volume and total peripheral vascular resistance, but did not affect heart rate. Nicorandil also showed a tendency to decrease coronary blood flow after an initial increase. All drugs tested decreased the difference in oxygen concentration between arterial and coronary sinus blood, indicating that these drugs increased the oxygen supply to the heart. Myocardial oxygen consumption was significantly decreased by more than 10 micrograms/kg of KRN2391, but was not affected by nifedipine. Nicorandil showed a tendency to decrease the myocardial oxygen consumption, though not significantly. Thus, KRN2391 may be useful to treat ischemic heart disease, because it increases the coronary blood flow and the oxygen supply to the heart, and decreases the afterload and the myocardial oxygen consumption. PMID- 1463371 TI - Stress-induced antinociception and GABAergic mechanism. AB - The antinociceptive effects of GABAergic agents in presence or absence of swim stress were investigated in mice, using the tail-flick test. Swim-stress, the GABAB agonist baclofen and the GABAA agonist muscimol raised the threshold of withdrawal reactions to nociceptive stimulation. The antinociception, induced by an interaction of stress and GABA agonists, was higher than that of stress or a GABA agonist alone. The GABAB antagonist phaclofen and the GABAA antagonists bicuculline and picrotoxin decreased the antinociceptive action induced by stress plus baclofen. Picrotoxin administration also decreased the response of baclofen. Picrotoxin and biculline, but not phaclofen, reduced the antinociceptive response induced by muscimol in stressed mice. Administration of picrotoxin, bicuculline or phaclofen alone did not decrease the stress-induced antinociception. The antagonists even increased the base line latencies in both normal and stressed mice. It is concluded that stimulation of both GABAA and GABAB receptor sites has an antinociceptive effect, but that the involvement of a GABAergic mechanism in stress-induced antinociception is unlikely. PMID- 1463372 TI - Effects of nimodipine and nicergoline on cerebrovascular injuries induced by activation of platelets and leukocytes in vivo. AB - Cerebral ischemia was induced in rabbits by selective injection of 4 beta-phorbol 12 beta-myristate-13 alpha-acetate (PMA) into the left carotid artery. PMA provoked intravascular platelet and neutrophil aggregation. After PMA injection, a significant decrease in platelet and neutrophil counts was observed. Platelet and neutrophil emboli caused ischemia of the brain and brain barrier damage with accumulation of sodium fluorescein in the cerebrospinal fluid. Regional tissue analysis showed an ipsilateral alteration of the cerebral energy state and increased lactate levels. Pretreatment with the prostacyclin infusion completely blocked the alterations in both platelet and leukocytes counts and decreased the cerebral energy failure. Nimodipine administration decreased the changes in platelet and neutrophil counts and prevented the development of both brain barrier and cerebral energy failure. Nicergoline had no statistically significant beneficial effect on PMA-induced cerebrovascular injury. PMID- 1463373 TI - Drug-induced modulation of endothelin-1 effects on the tone of electrically stimulated rat vas deferens. AB - The effects of endothelin-1 on the tone of the epididymal portion of the rat vas deferens were studied under treatment with drugs modulating the electrically evoked (single pulses, 1 msec, 80 V, 0.1 Hz) contractile responses. Endothelin-1 (0.01 nM-0.1 microM) concentration-dependently increased both the smooth muscle tone and the electrically stimulated contractions, the EC50 being 25.4 +/- 4.17 nM and 23.4 +/- 5.0 nM, respectively. The tonic contractions evoked by endothelin 1 persisted in the presence of 0.3 microM of tetrodotoxin or 10 microM of guanethidine. There were no significant differences in the EC50 values after tetrodotoxin (18.8 +/- 2.29 nM) or guanethidine (22.6 +/- 0.08 nM) as compared to controls, while the electrically stimulated contractile responses were completely inhibited. Clonidine (1, 3 or 10 nM) did not induce changes in the dynamic of the endothelin-1 effects on the tone. However, an increase in magnitude of the endothelin-1-induced contractions was observed on the background of the highest concentration of clonidine. Yohimbine, at concentrations of 1, 3 or 10 microM, significantly decreased the EC50 values for endothelin-1 to 16.4 +/- 1.02 nM, 16.1 +/- 1.60 nM and 8.09 +/- 1.15 nM, respectively. It is assumed that the development of the contractile effect of endothelin-1 on the tone of the electrically stimulated epididymal portion of the rat vas deferens does not depend on the integrity of the sympathetic innervation. However, a modulation of the endothelin-1 effects by yohimbine, rather than by clonidine, via postjunctional mechanisms, cannot be excluded. PMID- 1463374 TI - Enhancement by cimetidine of neuromuscular paralysis induced with atracurium in rats. AB - The neuromuscular action of cimetidine, the prototype of H2 antagonists, was examined in urethane-anaesthetized and mechanically ventilated rats that were paralyzed with the non-depolarizing agent atracurium. Cimetidine, administered i.v. at doses of 3.2 to 56.2 mg/kg (13 to 223 microM/kg), produced an immediate potentiation of a steady 50% atracurium paralysis which was observed within 28 +/ 5 sec and which plateaued after 24 +/- 3 min. The dose of cimetidine that produced a 50% potentiation during peak effect was 14.5 mg/kg (58 microM/kg) and was associated with a serum cimetidine concentration of 47.5 micrograms/ml (or 188 microM). In a separate experiment, cimetidine, administered i.v. in a dose of 56.2 mg/kg (223 microM/kg), shifted the atracurium dose-effect curve to the left by 1.32-fold. Cimetidine alone, at either 10 or 100 mg/kg, did not affect the neuromuscular function by itself. These results suggest that high doses of cimetidine potentiate the neuromuscular paralysis induced with atracurium. This effect is opposite to that noted previously with ranitidine, a newer H2 antagonist which reverses atracurium neuromuscular paralysis in rats. PMID- 1463375 TI - The John Stanley Coulter Lecture. Injury control: meeting the challenge. PMID- 1463376 TI - Combined and separate effects of eye patching and visual stimulation on unilateral neglect following stroke. AB - In Experiment 1, 11 of 13 stroke patients with left-sided neglect benefitted from monocular patching in at least one (of five) tests of neglect. This beneficial effect in most cases was limited to the period when the patch was worn. In Experiment 2, another group of stroke patients (n = 18) with left-sided neglect were tested in a line-bisection task with monocular patching and/or lateralized visual stimulation--a procedure previously shown to reduce neglect. Each procedure resulted in substantial benefits; the two procedures combined resulted in significantly larger benefits than either alone. As in Experiment 1, the degree of benefit of patching (alone or in combination with stimulation) was not related to several demographic factors. These findings suggest that monocular patching, together with lateralized visual stimulation, may significantly reduce neglect in daily activities and may be more beneficial than procedures requiring patients to be aware of their disorder and to use strategies for scanning the neglected side. PMID- 1463377 TI - Video feedback in occupational therapy: its effects in patients with neglect syndrome. AB - The use of video feedback in occupational therapy was evaluated in four patients with right hemisphere stroke and hemineglect. The study followed a single-case research experimental pretest, posttest, and follow-up (A1, B, A2, A3) design. Phases A1 and A2 included four observation times and phase A3 three, with 12 weeks for each patient. Three household tasks were assessed, and the patients' neglect behavior while performing these was videorecorded. One paper-and-pencil task using a modified Albert's test was also used, but not filmed. In the intervention program, the patients watched the film, which was stopped by the occupational therapist where the neglect behavior was significant. Through dialogue, the patients were led to perceive and interpret their neglect behavior, and strategies for relearning and remediation were recommended. The program seems to be effective for remediation and relearning a functional way of working. PMID- 1463378 TI - Electrogoniometric feedback: its effect on genu recurvatum in stroke. AB - The purpose of this study was to determine the effect of combining electrogoniometric feedback with contemporary physical therapy procedures for treatment of genu recurvatum following stroke. Twenty-six patients suffering knee hyperextension resulting from cerebrovascular disorders were allocated to either a control group or an experimental group. Both groups received treatment for knee hyperextension during two consecutive phases. During phase I the control group received physical therapy and the experimental group received electrogoniometric feedback as an adjunct to physical therapy. In phase II both groups received physical therapy alone. Each phase lasted four weeks, during which time patients were treated 45 minutes daily, five days every week. Subjects in the experimental group showed greater reduction in knee hyperextension. This was particularly evident in phase II when the difference between groups for reduction in knee hyperextension reached statistical significance (U = 40, p = 0.011). These results suggest that the addition of electrogoniometric feedback to standard physical therapy enhanced the effectiveness of treatment for genu recurvatum in stroke. PMID- 1463379 TI - Changes in nerve conduction and Pi/PCr ratio during denervation-reinnervation of the gastrocsoleus muscles of rats. AB - The purpose of this investigation was to study the changes in nerve conduction and phosphate metabolites of the gastrocsoleus muscles of rats during denervation reinnervation. Sixteen male Sprague-Dawley rats underwent unilateral crush denervation of the left sciatic nerves at the sciatic notch. Six rats were used for measurement of motor conduction latency and action potential amplitude of the gastrocsoleus muscle by stimulating the sciatic nerve at one, two and eight weeks after nerve crush. The other ten rats were designated for evaluation of the ratio of inorganic phosphorous (Pi) to phosphocreatine (PCr) by a 31P-phosphoenergetic spectrometer at two weeks and eight weeks after nerve crush. None of the sciatic nerves showed conduction to the gastrocsoleus at one or two weeks after nerve crush. At eight weeks postcrush, the motor conduction latency returned to within normal limits, whereas the action potential amplitude was only 55% of the normal. For the eight-week period of study, the Pi/PCr ratio of the normal control muscles ranged between 0.09 +/- 0.02 and 0.11 +/- 0.02 (mean +/- SD). The denervated muscles showed an increase of Pi/PCr ratio by 54% at two weeks postcrush, compared to the respective contralateral control sides. The ratios returned to the normal value by eight weeks postcrush. In summary, these data suggested that the metabolic recovery of the crush-denervated muscle followed the same pattern as the parameters of nerve conduction. PMID- 1463380 TI - Exploration of variables related to children's behavioral distress during electrodiagnosis. AB - To investigate variables potentially related to children's distress during electromyography/nerve conduction studies (EMG/NCS), mothers of 39 children ages two to 17 years reported the child's gender, experience with EMG/NCS, previous negative medical/dental experiences, general response to painful procedures, information-seeking style prior to procedures, health care fears, and information about the mothers' own health care fears and their anxiety regarding EMG/NCS. Physicians who performed the studies completed a behavioral distress checklist for each child. Results indicated that children exhibiting more behavioral distress were younger, had been uncooperative with previous painful procedures, were more likely to have had more negative medical/dental experiences, and had mothers who themselves reported greater fear and anxiety about undergoing EMG/NCS. Regression analyses indicated that previous negative medical/dental experiences accounted for additional variance in distress beyond that attributed to the child's age. Significant positive correlations between children's distress and specific previous negative medical/dental experiences were found. PMID- 1463381 TI - Center of mass location and segment angular orientation of below-knee-amputee and able-bodied children during walking. AB - This investigation compared the center of mass (COM) locations and segment angular orientations of the gait of below-knee-amputee (BKA) children to those of able-bodied (AB) children. Eleven AB children (mean age, 8.4 years) and three BKA children (mean age, 7.5 years) volunteered to participate as subjects. Film data (100 frames per second) of a typical walking stride, were collected for the children during four experimental sessions held at six-month intervals. Two 16mm cameras were used to obtain frontal and lateral views of the subjects. The same approximate rate of walking (1.2m/s +/- 10%) was enforced for all testing sessions and at least three trials of data were collected for each subject during each session. Segmental endpoints of each subject from the film of each camera were digitized and the direct linear transformation (DLT) method was used to obtain three-dimensional segmental location-time data for a complete stride. These data were then used to determine whole body COM locations and angular orientations for the segments. Discrete values describing normalized locations at touchdown, midsupport, and takeoff were determined for whole body COM and the angular orientation of the trunk, thighs, and legs. In the sagittal plane the COM was lower and more anterior for the BKA children when compared to that of the AB children. This was primarily due to the greater forward flexion of the trunk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463382 TI - Social discomfort and depression in a sample of adults with leg amputations. AB - We examined the relationship between social discomfort and depression in a sample of 89 adults with leg amputations at two outpatient clinics. It was hypothesized that individuals who reported being uncomfortable with social contacts involving acknowledgement of their amputation or prosthesis were more prone to depression than other patients. A set of questions addressing different aspects of social discomfort demonstrated internal consistency and were used as a scale. Social discomfort was significantly correlated with scores on the Center for Epidemiologic Studies-Depression Scale depression scale (r = .41). Multiple regression analysis showed that social discomfort was a significant independent predictor of depression, after holding constant the effects of age, gender, social support, time since amputation, reason for amputation, and perceived health. These data indicate that health care professionals should view the expression of social discomfort by amputee patients as a possible "marker" for depression. Further studies are planned to develop and validate an expanded social discomfort scale. PMID- 1463383 TI - Energy expenditure during walking in subjects with tibial rotationplasty, above knee amputation, or hip disarticulation. AB - The surgical treatment of osteosarcoma with a tibial rotationplasty seems to offer functional advantages in comparison with an above-knee amputation. It has not been established whether the functional advantages are accompanied by a lower rate of energy expenditure during walking. In children with a tibial rotationplasty (n = 15), an above-knee amputation (n = 6), or a hip disarticulation (n = 5), energy expenditure was measured during treadmill walking at various walking velocities. The subjects with a tibial rotationplasty were able to walk faster, but there were no differences between the groups in energy expenditure per unit time or per unit distance. Correction for confounding variables including age, sex, height, time since operation, level of activity, and support during walking in a multiple linear regression model did not reveal any significant differences in energy expenditure during walking between groups. 1992 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. PMID- 1463384 TI - Effects of cervical collars on standing balance. AB - The effect of cervical collars on standing balance in two age groups was examined. Twenty healthy women aged 60 to 78 years and 20 healthy women aged 18 to 29 years stood on a Kistler force platform with and without a cervical collar. Total, lateral and anteroposterior sway velocity were measured in each of three positions; long-base stance and eyes open, wide-base stance and eyes open, and wide-base stance and eyes closed. Analysis of variance showed no significant difference (p < .05) between the collar and no collar conditions for any of the standing balance measures. Older women had significantly more sway velocity (p < .001) than younger women during long-base standing both with and without the collar. Also they showed significantly more sway velocity in both the total (p < .01) and the anteroposterior (AP) directions (p < .001) of wide-base standing. There were no significant lateral sway velocity differences (p < .05). With eyes closed, sway velocity was greater in all age groups. In the wide-based condition there were significant differences in sway velocity between AP (p < .001) and total and lateral (p < .01). These results indicate that a cervical collar does not disturb standing balance in healthy women in the age groups tested. PMID- 1463385 TI - Quantifying handicap. PMID- 1463386 TI - Measurement standards for interdisciplinary medical rehabilitation. AB - Rehabilitation must address problems inherent in the measurement of human function and health-related quality of life, as well as problems in diagnosis and measurement of impairment. This educational document presents an initial set of standards to be used as guidelines for development and use of measurement and evaluation procedures and instruments for interdisciplinary, health-related rehabilitation. Part I covers general measurement principles and technical standards, beginning with validity, the central consideration for use of measures. Subsequent sections focus on reliability and errors of measurement, norms and scaling, development of measures, and technical manuals and guides. Part II covers principles and standards for use of measures. General principles of application of measures in practice are discussed first, followed by standards to protect persons being measured and then by standards for administrative applications. Many explanations, examples, and references are provided to help professionals understand measurement principles. Improved measurement will ensure the basis of rehabilitation as a science and nourish its success as a clinical service. PMID- 1463387 TI - Cephaloridine-induced nephrotoxicity in the Fischer 344 rat: proton NMR spectroscopic studies of urine and plasma in relation to conventional clinical chemical and histopathological assessments of nephronal damage. AB - The acute toxicological effects of the nephrotoxic antibiotic cephaloridine (CPH, 0-1500 mg/kg) in male Fischer 344 (F344) rats, have been investigated over 48 h using clinical chemistry, histopathology and proton nuclear magnetic resonance (1H NMR) spectroscopy of urine and plasma. High field (400 and 600 MHz)1H NMR urinalysis revealed increased excretion of lactic acid, acetoacetate, alanine, valine, lysine, glutamine and glutamate and a severe, time-dependent glycosuria. A major change observed in urine of CPH-treated animals was the dose-dependent increase in HB which may relate to altered energy metabolism. CPH also caused dose-dependent decreases in the urinary excretion of hippurate, allantoin and protein (conventional assay). This abnormal metabolic profile is consistent with a functional defect in the S1/S2 regions of the proximal tubule, and was confirmed by histology post mortem. Functional changes observed included elevations in blood urea nitrogen (BUN) and urine flow rate (UFR) and dose related decreases in urine osmolality. Spin-echo 1H NMR spectroscopic analysis of lyophilised plasma, reconstituted with 2H2O revealed an abnormal phase modulation of the methyl signal from free alanine and it is postulated that this is due to the release of transaminases from damaged tissue which via a reversible conversion to pyruvate, cause variable deuteration of alanine at the alpha-CH position. This observation suggests that 1H NMR spectral patterns are also dependent on the level of plasma transaminases and this may provide a novel indicator of tissue damage. PMID- 1463388 TI - On the bioactivation and genotoxic action of fluoranthene. AB - Fluoranthene (FA) was studied with respect to possible mechanisms of its high mutagenicity but low carcinogenicity, in comparison with the corresponding properties of benzo[a]pyrene (BaP), and with regard to the synergism of these two compounds shown by van Duuren and Goldschmidt (J Natl Cancer Inst 56, 1976, 1237). FA and BaP activated by S9 from Aroclor 1254 (PCB)-treated rats induce HPRT mutations in CHO cells with about equal effectiveness at the same exposure doses, which also lead to the same frequencies of repairable DNA adducts, enzyme induced strand breaks being used as an indirect measure of adducts to DNA. FA was also shown to be an efficient inducer of SCE in human peripheral lymphocytes cocultivated with PCB-treated HepG2 cells or with liver cells from PCB-pretreated rats. For the induction of SCE, FA and BaP were shown to act additively. From metabolic studies with liver microsomes from C57Bl/6 mice it is concluded that, whereas BaP induces the metabolism of BaP to the mutagenic epoxide, neither BaP nor FA is able to induce the metabolism of FA. In mutation experiments with V79 cells (XEM2) constitutive for P450 IA1 activity, BaP 7,8-diol but not FA 2,3-diol provokes a high frequency of HPRT mutations. In cells constitutive for P450 IA2 enzymatic activity FA and BaP are but weakly mutagenic and practically nonmutagenic, respectively. Due to the additivity of the genotoxic effects of FA and BaP, induction of an error-prone condition by the latter compound seems to be excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463389 TI - A mathematical approach to benzo[a]pyrene-induced hematotoxicity. AB - Benzo[a]pyrene (BaP) has been reported to exert a differential effect on murine hematopoiesis that is mouse strain specific. Interpretation of these results based solely on experimental data is restricted and leaves important questions unanswered. Therefore, a mathematical model of murine hematopoiesis was applied in order to: (1) identify the targets of BaP, (2) quantify the damage to target cells and (3) based on these results, interpret differences in strain susceptibility. Model analysis of the hematopoietic response of D2 and BDF1 mice to a daily oral administration of 125 mg/kg BaP showed that proliferating hematopoietic cells are the targets of BaP. Within this group it was found that: (a) erythropoietic cells were the most susceptible to BaP, (b) granulopoietic cells showed a susceptibility half that of erythropoietic cells and (c) the susceptibility of stem cells ranged between that of erythropoietic and granulopoietic cells. This damage pattern was the same for both strains, indicating that the difference between the strains was quantitative. As cell destruction rates were about 3-fold higher for D2 than BDF1 mice, it was concluded that D2 mice were about three times as susceptible to BaP as BDF1 mice. The study showed that the mathematical model, in addition to experimental methods, provided an efficient tool for the analysis of BaP hematotoxicity. PMID- 1463390 TI - Abnormal thymus development and impaired function of the immune system in rats after prenatal exposure to aciclovir. AB - Aciclovir (synonym: acyclovir) causes abnormal thymus development in rats. After treatment on day 10 of gestation a weight reduction of the organ is obvious in 21 day-old fetuses which persists postnatally. Adult male rats exposed in utero to one or three injections of 100 mg aciclovir/kg body wt given to the dam on day 10 of pregnancy showed a reduction of the thymus weight to 333 +/- 158 mg and 276 +/ 61 mg (control: 428 +/- 92 mg; n = 10). Corresponding alterations were detectable in female offspring. Liver weight was also decreased and spleen weight (in relation to body wt) was significantly increased in the offspring after the three exposures. In a host resistance model with Trichinella spiralis the function of the immune system of rats prenatally exposed to aciclovir was examined. Six weeks postnatally 10-12 randomly selected male rat offspring of one control and two treatment groups (1 or 3 injections of 100 mg aciclovir/kg body wt on day 10 of gestation) were infected orally with 500 Trichinella spiralis muscle larvae. Before and several times after the infection blood was taken from a tail vein or obtained by decapitation for examination of the antibody titers (IgM, IgG, IgA, IgE) to antigens of T. spiralis. Six weeks after the infection the weight of relevant organs was determined and tongue preparations were used for T. spiralis muscle larvae counting. Aciclovir exposed animals showed a different immune response than control rats. IgM titers in both treatment groups were higher than in controls two weeks after the infection but not different by the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463391 TI - Distribution and inducibility of a P450I activity in cellular components of the avian immune system. AB - The level of expression of the cytochrome P450 system in an immune tissue could influence the sensitivity of that immune tissue to damage by xenobiotics. The capacity of immune organs and their cellular components for P450I-catalyzed metabolism was assayed in the 4-week-old chicken using the P450I-specific ethoxyresorufin-O-deethylase (EROD) assay and the P450I-inducer, 3,4,3',4' tetrachlorobiphenyl (TCB). After induction by TCB, EROD was detectable in microsomes from whole thymus, bursa and in peritoneal exudate cells (containing primarily macrophages) at levels of 28.3, 7.2 and 1.3 pmol/mg microsomal protein/min, respectively; the level in control liver was 89.9 pmol/mg microsomal protein/min. No activity was detected in these immune tissues without induction. The P450I specific in vitro inhibitor, alpha-naphthoflavone (NF) inhibited the TCB-induced liver and immune tissue EROD by 50% at concentrations in the range of 0.07-0.1 microM. The cellular distribution of EROD in the bursa and thymus was studied in lymphocytes and supporting tissue cells after their separation by density gradient centrifugation. Much higher TCB-induced EROD was detected in immune tissue supporting cells than in lymphocytes, particularly in the thymus. The P450I in the supporting tissue of the bursa and thymus at 1 week post-hatch was also measured after eradication of the lymphocytes in both immune tissues by in ovo administration of CP. TCB-induced EROD was 12-fold higher in the lymphocyte-depleted thymus than in normal thymus, with a less marked but similar pattern in the bursa.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463392 TI - Reproductive toxicity and toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects of single doses on the testis of male rats. AB - The effects of a single dose of TCDD on the testis were studied in rats. The animals were treated (subcutaneously) once with TCDD doses of 0, 0.5, 1.0, 3.0, 5.0 micrograms/kg body weight. Doses of 3.0 or 5.0 micrograms TCDD/kg reduced the number of spermatids/testis significantly (60% of the controls). Electron microscopic inspection revealed that both doses led to a dissolution on the germinal epithelium. Altered germ cells at all developmental stages occurred in all testes evaluated. Doses of 0.5 or 1.0 micrograms TCDD/kg did not induce any effects in the testis; therefore, under these experimental conditions of single exposure to rats the dose of 1.0 micrograms TCDD/kg can be considered as NOAEL. PMID- 1463393 TI - Hepatotoxic interaction between carbon tetrachloride and chloroform in ethanol treated rats. AB - The effect of coadministration of CHCl3 on CCl4-induced hepatic damage was investigated at low dose inhalation. Coexposure of CHCl3 did not influence CCl4 induced changes in any index of hepatic damage in control rats. Coadministration of CHCl3, however, enhanced CCl4 (10 ppm)-induced hepatic damage of ethanol treated rats in a dose- and duration-dependent manner: simultaneous exposure of 50 ppm CHCl3 potentiated CCl4-induced increase in plasma GPT activity and number of necrotic hepatocytes; the enhancement of CCl4-induced hepatic damage by 50 ppm CHCl3 was found over the 4 h exposure; simultaneous exposure of 10 and 25 ppm CHCl3 potentiated the CCl4-induced increase in liver malondialdehyde (MDA) content. In contrast, coadministration of 50 ppm trichloroethylene and 200 ppm 1,1,1-trichloroethane decreased CCl4-induced increase in plasma GPT activity, though these exposures did not influence the liver MDA content. These results suggest that the concentration of 10 ppm CCl4 may be significant for CHCl3 to potentiate the hepatic damage caused by CCl4 in ethanol-treated rats. Heavy drinkers may have a higher hepatotoxic risk for a mixture of CCl4 and CHCl3 than for a single exposure to CCl4 or CHCl3, and a particular attention should be therefore given to the joint exposure to CCl4 and CHCl3. PMID- 1463394 TI - Effect of tetrakis-mu-3,5-diisopropylsalicylatodiaquodicopper(II) on the status of reduced glutathione in freshly isolated hepatocytes. AB - Effects of different concentrations of tetrakis-mu-3,5 diisopropylsalicylatodiaquodicopper(II) (Cu(II)2(3,5-DIPS)4(H2O2)2) on the reduced status of glutathione (GSH), the major nonprotein thiol in tissues, were investigated using freshly isolated hepatocytes. Cu(II)2(3,5-DIPS)4 below 100 microM did not have any significant effects on either the GSH content or viability of the hepatocytes, but at 150-250 microM it decreased both parameters after 1 h of incubation. The decrease in cellular GSH was not followed by an increase in the oxidized form of GSH (GSSG) in the cell suspension. The addition of deferoxamine with Cu(II)2(3,5-DIPS)4 to the hepatocyte suspension prevented depletion in GSH content and loss of cell viability by Cu(II)2(3,5-DIPS)4. Both GSH depletion and loss of cell viability were found to be Cu(II)2(3,5-DIPS)4 dose dependent. From these results, it appears that Cu(II)2(3,5-DIPS)4 penetrated the cell membrane and acted by decreasing the GSH level by forming a copper glutathione complex. PMID- 1463395 TI - Increased urinary cadmium excretion and its relationship to urinary N-acetyl-beta D-glucosaminidase activity in smokers. AB - To assess the renal effects of low-level exposure to cadmium due to smoking we examined blood and urinary levels of cadmium and urinary excretions of N-acetyl beta-D-glucosaminidase (NAG), beta 2-microglobulin (BMG) and metallothionein in 94 male workers aged 18-55 years. Both blood and urinary cadmium levels indicated excess exposure to cadmium caused by smoking. The urinary cadmium concentration ranged between 0.1 and 5.0 micrograms/g creatinine and increased significantly with age in the smokers. Neither urinary NAG nor BMG was increased in the smokers compared from non-smokers. A positive relationship between urinary cadmium and metallothionein was obtained not only in the smokers but also in the non-smokers. Furthermore, in the smokers urinary cadmium and metallothionein was positively related with urinary NAG. Since NAG in urine mostly originates from tubular cells by lysosomal exocytosis, the results may reflect an early cadmium effect on the lysosomal functions. Inhibitory effect of cadmium on the lysosomal degradation activities was discussed as a possible explanation of the positive relationship of urinary cadmium and metallothionein to urinary NAG. PMID- 1463396 TI - External transscleral posterior chamber lens fixation. PMID- 1463397 TI - The use of animals in medical education. PMID- 1463398 TI - Aminoglycoside toxicity: a comment. PMID- 1463399 TI - Intravitreal aminoglycoside toxicity revisited. PMID- 1463400 TI - Late infectious endophthalmitis from exposed glaucoma setons. PMID- 1463401 TI - Tarsotomy for the treatment of cicatricial entropion. PMID- 1463402 TI - Successful treatment of gram-negative endophthalmitis with intravitreous ceftazidime. PMID- 1463403 TI - Chronic postoperative Rhodotorula endophthalmitis. PMID- 1463404 TI - Pituitary apoplexy precipitating acute angle closure. PMID- 1463405 TI - Recovery from pulsed-dye laser retinal injury. PMID- 1463406 TI - Kaposi's sarcoma of the eyelids: response to radiotherapy. PMID- 1463407 TI - Health Access America revisited and revised. PMID- 1463408 TI - Visual function and driving safety. PMID- 1463409 TI - Assessment of driving performance in patients with retinitis pigmentosa. AB - The driving performance of 21 subjects with retinitis pigmentosa (RP) and varying degrees of peripheral field loss was compared with the performance of 31 normally sighted control subjects who did not differ statistically from the subjects with RP in age, gender, years of driving experience, or miles driven per year. Driving performance was assessed by self-reported accident frequency and by an evaluation of performance on an interactive driving simulator. A significantly greater proportion of individuals had self-reported accidents in the RP group than in the normal group. Likewise, a significantly greater proportion of subjects with RP than normal subjects had accidents on the driving simulator. Logistic regression analyses indicated that binocular horizontal field extent and binocular field area significantly differentiated between those having no self-reported accidents and those subjects with RP having one or more self-reported accidents. Because the simulator indexes were correlated with visual field measures for the subjects with RP, no additional information was incorporated into the regression model by adding the simulator measures. Therefore, our results indicate that visual field loss is a primary correlate of automotive accidents in individuals with RP. PMID- 1463410 TI - Diode laser photocoagulation for retinopathy of prematurity. Preliminary results. AB - In a prospective, randomized clinical trial comparing transscleral cryotherapy with laser photocoagulation in the treatment of "threshold" stage 3+ retinopathy of prematurity, 32 infants were treated with diode laser photocoagulation in one eye. Twenty-eight infants have been followed up for at least 3 months, and seven have been followed up for at least 1 year. Twenty-five of 28 eyes treated with diode laser photocoagulation and followed up for at least 3 months have undergone regression. Of 24 fellow eyes treated with cryotherapy and followed up for at least 3 months, 20 have undergone regression. All seven eyes treated with diode laser photocoagulation and followed up for at least 1 year have undergone regression. Of seven fellow eyes treated with cryotherapy and followed up for at least 1 year, all have undergone regression. Our results suggest that diode laser photocoagulation is as effective as cryotherapy in the treatment of retinopathy of prematurity. PMID- 1463411 TI - Posterior chorioretinopathy and retinal detachment after organ transplantation. AB - Four patients, three after renal transplantation and one after heart-lung transplantation, developed visual loss in both eyes associated with geographic zones of disruption and coarse clumping of the pigment epithelium in the posterior fundi. Secondary retinal detachment occurred bilaterally in three patients. Localized choroidal intravascular coagulation is the suspected but unproven cause. PMID- 1463412 TI - Pneumatic retinopexy perfluoroethane (C2F6) in the treatment of rhegmatogenous retinal detachment. AB - Due to differences in expansile properties and duration, perfluorethane gas may offer advantages over other gases presently used for pneumatic retinopexy. Seventeen eyes with retinal detachments with single retinal breaks or groups of breaks no greater than 1 clock hour in extent were prospectively treated with perfluoroethane gas injection and retinocryopexy and followed up for a minimum of 6 months. Twelve eyes (71%) were attached with one procedure, and five eyes (29%) were attached with two or three procedures. Post-operative proliferative vitreoretinopathy occurred in two eyes (12%), new or missed breaks in three eyes (18%), and premacular fibroplasia in one (6%) eye. No eyes had an apparent progression of cataracts. Seven (88%) of eight eyes with preoperative macular detachments had improved visual acuity after surgery. All nine eyes (100%) with preoperative macular attachment had the same or improved visual acuity after surgery. The efficacy of perfluoroethane appears similar to that of other perfluorocarbon gases. PMID- 1463413 TI - Peripheral visual field testing in glaucoma by automated kinetic perimetry with the Humphrey Field Analyzer. AB - A Humphrey automated perimeter was used to measure the central 24 degrees of vision with static threshold targets and the peripheral field with two automatic kinetic stimuli in 100 eyes of 100 patients with glaucoma or a suspicion of glaucoma and to compare the additional information gained with the peripheral tests. The peripheral visual field supported the diagnosis made with central field testing in approximately one third of the eyes and added additional diagnostic information in another fourth of the cases. In 4% of patients a normal central field was associated with a glaucomatous peripheral defect. Virtually all peripheral defects were in the nasal quadrant, and the more sensitive isopter uncovered the vast majority of the defects. PMID- 1463414 TI - Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension. AB - In a randomized, double-masked, parallel study, one drop of 0.003% (1 microgram; n = 9) or 0.01% (3 micrograms; n = 10) PhXA34, a new phenyl-substituted prostaglandin F2 alpha analogue (13,14-dihydro-15[R,S]-17-phenyl-18,19,20-trinor prostaglandin F2 alpha-1-isopropyl ester), or its vehicle (n = 10) was applied topically twice daily for 6 days to one eye in each of 29 patients with ocular hypertension. Compared with either baseline, contralateral, or vehicle control values, PhXA34 caused a significant (P < .001) dose-dependent reduction of intraocular pressure. The reduction lasted at least 12 hours after each drop and 24 to 48 hours after the last drop, with a significant (P < .0001) mean +/- SEM reduction of as much as 10 +/- 1 mm Hg (40%). Conjunctival hyperemia was not produced by 0.003% PhXA34, but was noted in some eyes treated with 0.01% PhXA34, and after repeated tonometry with either concentration. The prostaglandin analogue did not produce clinically obvious miosis, anterior chamber flare or cellular response, or any subjective adverse effects. PhXA34 is a potent, effective, and well-tolerated ocular hypotensive agent based on our results in this small, short-term study. Its potential as a new drug for glaucoma therapy warrants further investigation in long-term, larger studies. PMID- 1463415 TI - Peters' anomaly and associated congenital malformations. AB - We reviewed the clinical findings in 29 patients with Peters' anomaly. There was developmental delay in 15 patients, congenital heart disease in eight patients, external ear abnormalities in five patients, structural defects of the central nervous system in four patients, genitourinary malformations in four patients, cleft lip/palate in three patients, hearing loss in three patients, spinal defects in two patients, and single cases of other less common defects. One patient had fetal alcohol syndrome; one, Pfeiffer's syndrome; and one, short stature, ulnar hypoplasia, and joint laxity. Colobomatous microphthalmia was present in seven patients, and persistent hyperplastic primary vitreous in three patients. Ten patients developed glaucoma, and three had retinal detachment unrelated to ocular surgery. Peters' anomaly may be due to a developmental field defect, or the complex ocular and systemic malformations may be the result of a contiguous gene syndrome or of a defective homeotic gene controlling the development of the eye and other body structures. PMID- 1463416 TI - Surgical dissection of capillary hemangiomas. An alternative to intralesional corticosteroids. AB - Intralesional corticosteroids are often successful in reducing the size of functionally significant capillary hemangiomas. While they may have a better benefit-risk ratio than some earlier treatment methods, a number of serious complications have been reported recently. We believe these resulted from the hemodynamic continuity of capillary hemangiomas with the orbital and systemic circulation and that intralesional injections are intravascular. Surgery has generally been avoided because capillary hemangiomas are not encapsulated and piecemeal resection can produce significant bleeding. In carefully selected patients, we have used a surgical approach that involves dissection on the tumor's surface without entering its substance. Hemangiomas were removed en bloc from five patients with insignificant blood loss and excellent anatomic restoration. PMID- 1463417 TI - Endoscopy of the lacrimal outflow system. AB - Management of obstructions in the lacrimal drainage system would be greatly aided by improvements in the ability to visualize the blockages. We describe a new method of observation using miniature fiberoptics to view the entire lacrimal excretory system. We employed flexible endoscopes of fiberoptic bundles with outside diameters of from 0.5 to 0.7 mm. These endoscopes were inserted through the puncta and canaliculi. Sixteen patients were examined. A range of pathologic conditions were found, including slightly stenosed passages and severely destroyed canalicular mucosal lining. Our results indicate that this technique is feasible and useful in the diagnosis of lacrimal excretory disease. PMID- 1463418 TI - Pseudoexfoliation syndrome. Ocular manifestation of a systemic disorder? AB - The pseudoexfoliation syndrome has recently been suggested to represent the local manifestation of a more widespread disorder. In this study, a case of classic bilateral pseudoexfoliation syndrome with systemic distribution of pseudoexfoliation material involving a variety of organ systems is described. Using transmission electron microscopy, typical pseudoexfoliation fibers were identified in autopsy tissue specimens of skin, heart, lungs, liver, kidney, and cerebral meninges in addition to the classic intraocular locations. The pseudoexfoliation material was mainly localized to connective-tissue portions or septa traversing the various organs. The pseudoexfoliation fibers were consistently associated with connective-tissue components, particularly fibroblasts and collagen and elastic fibers; myocardial tissue specimens; and heart-muscle cells. These findings provide evidence for the systemic nature of the pseudoexfoliation syndrome, which apparently involves an aberrant connective tissue metabolism throughout the body. PMID- 1463419 TI - Pseudoexfoliative fibrillopathy in visceral organs of a patient with pseudoexfoliation syndrome. AB - Evidence is increasing that pseudoexfoliative material develops in widespread areas of skin and parabulbar tissues as well as intraocularly. To determine whether this process is even more diffusely distributed, ultrastructural examination was performed on visceral and ocular tissues of a patient with long standing glaucoma found to have bilateral ocular pseudoexfoliation at autopsy. Aggregates consistent with pseudoexfoliative material were present in the lung, heart, liver, and gallbladder, in addition to the classic intraocular sites. The aggregates were in the fibrovascular septa and stroma of these organs, most frequently adjacent to elastic and oxytalan fibers. They stained positively for elastin and human amyloid P protein, like the ocular sites, in preliminary immunologic testing. Rare atypical aggregates were seen in one of the four control patients. These findings suggest that pseudoexfoliation is a systemic process involving abnormal matrix synthesis, particularly as related to elastic tissue components. PMID- 1463420 TI - Rapid detection of gram-negative endotoxin contamination of contact lens saline solutions. AB - The use of the limulus amoebocyte lysate for the early and rapid detection of gram-negative endotoxin contamination of contact lenses and their solutions could reduce the risk of a keratitis developing that is associated with these devices. Using multiple aliquots from 17 unopened brands of commercially available contact lens saline solutions (15 for soft, two for hard), plus multiple aliquots from these solutions mixed with bacterial endotoxin, we evaluated the ability of two limulus amoebocyte lysate (0.125 endotoxin units/mL) products to detect the presence or absence of gram-negative endotoxin contamination. Sensitivity ranged from 65% (11/17) to 82% (14/17) when the solutions were tested undiluted. When diluted 1:8, the sensitivity increased to 100%. Specificity was 100% for undiluted and diluted specimens. The solutions used for hard contact lenses had the highest false-negative results. The limulus amoebocyte lysate can be used to detect the presence of gram-negative endotoxin in contact lens solutions. PMID- 1463421 TI - Outflow obstruction in pigmentary and primary open angle glaucoma. AB - To localize the site of outflow obstruction in glaucoma, we evaluated the trabecular meshwork tissues by morphometric methods. Thirty-three specimens from 27 patients with primary open angle glaucoma (n = 13), pigmentary glaucoma (n = 4), and pigment dispersion syndrome (n = 2), and from nonglaucomatous normal subjects (n = 8) were compared. In these specimens, the extent of aqueous channels and the area occupied by these channels where they terminate in cul-de sacs were measured. In 32 nonglaucomatous normal specimens (six of the eight mentioned plus an additional 26), we discovered that 94% of the surface area of the cul-de-sacs is lined by trabecular cells. These measurements were used to calculate the resistance to aqueous outflow offered by cul-de-sacs. Three new concepts are advanced in this report: (1) the cul-de-sacs provide a major portion of the normal outflow resistance, (2) the cul-de-sac area is markedly reduced in pigmentary glaucoma and primary open angle glaucoma, accounting for a major portion of the increase in resistance in these conditions, and (3) macrophages are the major cell type responsible for trabecular meshwork clearance of pigment and debris. A common pathophysiologic sequence of events is proposed for the development of glaucoma in pigmentary glaucoma and primary open angle glaucoma. PMID- 1463422 TI - Juxtacanalicular tissue in pigmentary and primary open angle glaucoma. The hydrodynamic role of pigment and other constituents. AB - We tested the hypothesis that obstruction of the juxtacanalicular tissues, by melanin granules in pigmentary glaucoma and by other impermeable material in primary open angle glaucoma, leads to the development of a chronic glaucomatous condition. The distribution and concentration of melanin and other impermeable materials in the juxtacanalicular tissues and elsewhere in the trabecular meshwork was determined in 13 specimens. Six specimens were from patients with pigmentary glaucoma, two from patients with pigment dispersion syndrome, and three from patients with primary open angle glaucoma, as well as two from normal subjects. The effect of these materials on flow resistance was estimated using two hydrodynamic models. In model A, the electron-lucent spaces of the juxtacanalicular tissue were assumed to be open spaces, while in model B, these spaces and spaces filled with ground substance were assumed to be gel filled. In pigmentary glaucoma, 3.5% of the pigment was found in the juxtacanalicular tissue, while 96.5% was found in the corneoscleral and uveoscleral tissues. Permeabilities calculated according to model A were much higher than those expected from estimates of outflow facility in all groups, in agreement with the previous report of Ethier et al. The gel-filled spaces available for fluid flow, as determined by model B, showed no statistically demonstrable differences (pigmentary glaucoma, 32.9%; primary open angle glaucoma, 36.6%; pigment dispersion syndrome, 43.4%; normal, 44.1%). Furthermore, the amount of pigment present in the juxtacanalicular tissue was determined to have a negligible influence on permeability. Thus, the development of the chronic glaucomatous condition cannot be directly attributed to pigment accumulation in the juxtacanalicular tissue in pigmentary glaucoma. PMID- 1463423 TI - Response of the retinal pigment epithelium to selective photocoagulation. AB - Multiple short argon laser pulses can coagulate the retinal pigment epithelium selectively, while sparing the adjacent neural retina and choroid; in contrast, continuous-wave laser irradiation typically damages the neural retina and choroid. The healing response to selective photocoagulation of the retinal pigment epithelium was studied in rabbits during a period of 4 weeks. The lesions were never visible ophthalmoscopically. During the healing period, the epithelium was reformed by a single sheet of hypertrophic retinal pigment epithelial cells. In contrast to continuous-wave photocoagulation, only minimal inflammatory response was found. Retinal pigment epithelial cells showed clear signs of viability, eg, phagocytized outer segments. The local edema in the photoreceptor layer and subretinal space found in the early stage disappeared when the blood retinal barrier was reestablished. The choriocapillaris remained unaffected. No subsequent damage to the photoreceptors was found. This type of photocoagulation may be useful for retinal pigment epithelium-related diseases, eg, diffuse diabetic macular edema. PMID- 1463424 TI - Medial canthoplasty with microplate fixation. AB - Six patients with malpositioned or surgically excised medial canthal tendons underwent repair with titanium microplate, and two patients underwent repair with titanium miniplate fixation. The T-shaped rigid fixation plates were chosen for medial canthal reconstruction to allow for stabilization of the plate along the anterior lacrimal crest and extension of the plate over the posterior lacrimal crest. The medial canthal tissue was reattached to the titanium plate with 3.0 polypropylene (Prolene) suture. This technique appears to be safer, faster, and, in many cases, more effective than traditional techniques for reconstruction of the medial canthus after tendon avulsion or loss from excision of cutaneous carcinoma. PMID- 1463425 TI - The orbital muscle of Muller. PMID- 1463426 TI - Binding of calcium to myoplasmic buffers contributes to the frequency-dependent inotropy in heart ventricular cells. AB - In guinea-pig ventricular cells, the Ca2+ buffer capacity of the myoplasm was estimated from the ratio of ionized calcium (from Indo-1 fluorescence) through total calcium (ionized plus bound calcium, from x-ray microprobe analysis). During post-rest potentiation (1 Hz paired-pulses in voltage-clamp), where diastolic sarcomere length remained nearly constant, Ca2+ buffer capacity slowly fell from 5500:1 to 700:1 suggesting that slow Ca2+ binding sites became saturated. We discuss that frequency-inotropy depends not only on the replenishment of intracellular stores with Ca2+, but also on binding of Ca2+ to these slow sites; the slow Ca2+ sites could complete with the fast activator sites on troponin C for systolic Ca2+, or they could enhance the Ca2+ affinity of the fast Ca2+ sites on troponin C by cooperative interaction. PMID- 1463427 TI - Release kinetics of cardiac troponin T in coronary effluent from isolated rat hearts during hypoxia and reoxygenation. AB - A newly developed troponin T (TnT) test for the detection of myocardial cell necrosis has been reported to be very efficient in the detection of acute myocardial infarction. The aim of the present study was to determine whether cardiac TnT in coronary effluent from isolated heart perfused with albumin-free perfusion medium could be detected using the enzyme-linked immuno-sorbent assay developed by Katus et al. Isolated rat hearts were perfused according to the method of Langendorff. Coronary flow rate was measured by timed collection of the coronary perfusate that dripped from the hearts during 5 h of hypoxia (protocol A) or 4 h of hypoxia followed by 1 h of reoxygenation (protocol B). Creatine kinase (CK) and lactate dehydrogenase (LD) levels were compared with that of TnT. Myocardial adenine nucleotides were measured by HPLC. There was a strong correlation between TnT levels in albumin-free coronary effluent and TnT levels in coronary effluent diluted 1:1 with 5% bovine serum albumin (r = 0.996, N = 72). The coefficients of correlation between TnT and CK or LD during hypoxia and reoxygenation were 0.891 (N = 88) and 0.871 (N = 88), respectively. The coefficient of correlation between CK and LD was 0.993 (N = 88). There were no significant differences in either the decrease of coronary flow or the increase of TnT content between the hearts in the two protocols. There was no significant correlation between sigma TnT and energy charge of adenine nucleotides. These results indicate that cardiac TnT levels can be easily measured in albumin-free coronary effluent of isolated heart preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1463429 TI - Nitric oxide (EDRF) enhances the vasorelaxing effect of nitrendipine in various isolated arteries. AB - Recent studies suggest endothelium to be involved in the vasorelaxation of calcium antagonists of the 1,4-dihydropyridine type, which may at least in part be mediated by endothelium-derived relaxing factor (EDRF = NO). To study this effect further, the influence of L-NG-nitro arginine (L-NNA), a specific inhibitor of EDRF-synthesis, on nitrendipine-induced vasorelaxation was examined in different isolated porcine arteries. Coronary, basilary, and tail arteries were bathed in Krebs-Henseleit solution and endothelial function was verified by means of substance P, an EDRF releasing neuropeptide. Vasorelaxation of nitrendipine in PGF2 alpha-precontracted arteries was studied in the presence and absence of L-NNA. Nitrendipine-induced vasorelaxation was markedly reduced by the addition of L-NNA in all vessels studied. Tachyphylactic effects of nitrendipine could be excluded. The obtained results may be explained by an enhancement of nitrendipine action by basally released EDRF, alternatively, by an increased EDRF release induced by this calcium antagonist. Therefore, in a second series of experiments the release of EDRF was studied in isolated coronary arteries under cumulative application of nitrendipine. Using the nitric oxide scavenging properties of oxyhemoglobin, EDRF release was measured spectrophotometrically by means of methemoglobin formation. The application of nitrendipine resulted in a concentration-dependent increase in the extinction rate, indicating an increased release of NO which could be inhibited by preincubation with L-NNA. It may be concluded that, in functionally intact vessels, vasorelaxation induced by nitrendipine may additionally be mediated by an increased release of EDRF. PMID- 1463428 TI - Improvement of relaxation velocity parameters by calcium channel blockers in the aging rabbit myocardium. AB - Normal aging in man is known to be associated with a reduction in left ventricular diastolic function, including the rates of relaxation and filling. Calcium channel blockers have been reported to improve left-ventricular diastolic function in patients with various forms of heart disease. Clinically, the action of calcium channel blockers may be related to either a direct myocardial effect or may be secondary to the peripheral or coronary vasodilation effects. The purpose of this study is to investigate a possible direct effect of calcium channel blockers on modulation of the reported age-related reduction in myocardial relaxation. The direct effects on myocardial relaxation of the dihydropyridine calcium channel blocker, nifedipine, were studied in isolated, perfused interventricular septa and left-ventricular wall from eight young (ages 9 to 18 months) and 14 old (ages 3 to 5 years) rabbits. Septa were perfused with oxygenated Ringer's solution and paced at 48 beats/min. Maximum relaxation velocity per unit of developed tension [-dT/dt]/T, and relaxation time per unit of developed tension tR/T were continuously measured before and after infusion of calcium channel blockers. In absence of drugs, the older rabbits demonstrated a mean [-dT/dt]/T which was 32% lower (p < 0.003) and a mean tR/T which was 45% higher (p < 0.005) than the younger rabbits. When nifedipine was introduced at concentrations > 10(-8) M equivalent to doses above the therapeutic free-plasma concentration in humans, all contraction and relaxation parameters were depressed. However, at lower doses, equivalent to doses in the clinical therapeutic range, [-dT/dt]/T was increased in the older rabbit septa by 18% in the presence of nifedipine. tR/T was shortened in the older rabbit septa by 17% in the presence of nifedipine. Myocardial relaxation in older rabbits after drug infusion approximated these parameters in the younger rabbits prior to drug infusion (P = NS). Calcium channel blockers had similar beneficial effects on the relaxation properties of the myocardium in younger rabbits. All beneficial effects were observed at concentrations of calcium channel blockers which were within and below the clinically therapeutic range of plasma free drug concentration, i.e., 5 x 10(-9) to 4 x 10(-8) M. Potential differences in relaxation effects related to different segments of the myocardium and different mechanical recording vectors were evaluated. Isolated left ventricle preparations from aging rabbits demonstrated improvements in tR/T and [-dT/dt]/T similar to those observed in the septum. Furthermore, improvement in mechanical function along the y-axis and x-axis vectors of the septum was similar.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1463430 TI - Changes in heart rate by verapamil during carotid sinus stimulation in patients with hyperparathyroidism, pre- and postoperatively. AB - It has been investigated whether calcium- and verapamil-dependent sensitivities of carotis baroreceptors also exist in man. To answer this question, we pre- and postoperatively measured changes in heart rate during carotid sinus stimulation before and after intravenous administration of 5 mg verapamil in 23 patients with primary hyperparathyroidism. Findings during hypercalcemia were as expected: a more pronounced reduction of heart rate at comparatively low calcium levels. During normocalcemia, we found an opposite effect: a more pronounced reduction at relatively high calcium levels, which was statistically significant. This fact could be explained according to our interpretation. In previous reports, local effects on baroreceptors were examined, whereas we measured the combined effect of several calcium actions. As expected, verapamil attenuated the decrease in heart rate which, however, was not statistically significant. PMID- 1463431 TI - Ischemia and reperfusion injury in isolated rat heart: effect of reperfusion duration on xanthine oxidase, lipid peroxidation, and enzyme antioxidant systems in myocardium. AB - The aim of this work was to assess the catalytic activity of xanthine oxidase, the level of lipid peroxides and enzymic antioxidant systems in isolated rat heart muscle subjected to a globally partial ischemia followed by varying durations of reperfusion. After 40 min of globally partial ischemia (residual perfusion flow rate: 0.1 ml/min), four different durations of reperfusion were investigated (0, 20, 40, and 60 min). After each experimental ischemia/reperfusion sequence, the heart was frozen in liquid nitrogen. Lipid peroxides were assayed in the cardiac homogenate and the catalytic activity of xanthine oxidase and enzymic antioxidant systems (glutathione peroxidase, superoxide dismutase and catalase) were determined in the centrifuged supernatant. In the different experimental protocols studied in this work, there was no significant increase in the activity of cardiac xanthine oxidase or in the level of lipid peroxides when compared to the non reperfused or to the continuously perfused hearts. Indeed, enzymic antioxidant systems were also not significantly modified in the different periods of reperfusion when compared to control hearts (continuously perfused hearts). These results suggest that xanthine oxidase is apparently not a major source of free radicals in the course of an ischemia-reperfusion sequence in heart muscle, in particular, if we consider the early phases of reperfusion. The process of lipid peroxidation, assessed by assaying thiobarbituric acid reactants, is not a predominant phenomenon of reperfusion-induced injury, at least in the experimental model used here. However, enzymic antioxidant systems investigated in this study do not seem modified. This could mean that the small quantity of oxygen free radicals produced does not overwhelm the enzymic antioxidant systems of myocardium which is in agreement with peroxidatized lipid results. PMID- 1463432 TI - Causative role of coronary microvessels for the development and progression of chronic myocardial lesions in spontaneously hypertensive rats (SHR). AB - The pathomechanisms responsible for the development and progression of myocardial alterations in hypertensive heart disease are largely unknown. Using newly developed preparation and measuring procedures in 78 SHR and 82 controls aged 3 78 weeks, topological relations were detected between focal morphological appearances of chronic myocardial ischemia (fml.) and pathological microvessel (mv.) reactions characterized by morphometric signs of chronic contractions. The smallest ramifications are of particular pathogenic importance. A generalized peak of pathological mv. reactions between the 16th and 24th weeks is responsible for the development of first fml. The further progression of the area density of fml. from 1.26 +/- 0.85% (24th week) to 31.82 +/- 8.60% (78th week) is attributable to the further increase in pathological mv. reactions caused by organ-specific influences. The histological and morphometric findings suggest that the pathological mv. reactions are aggravated by their own effects at the local level. PMID- 1463433 TI - Influence of selective autonomic decentralization on myocardial deoxyglucose uptake initiated by cardio-cardiac reflexes. AB - The aim of this study was to evaluate the effect of autonomic reflexes as initiated by stimulation of the right recurrent cardiopulmonary nerve afferent axons on myocardial deoxyglucose uptake and to determine how such uptake can be modified by selective neural ablation. The afferent axon in the right recurrent cardiopulmonary nerve was stimulated 30 s/min for 1 h in five anesthetized open chest dogs in which 14-C labeled deoxyglucose was i.v. injected at the beginning of the stimulation period. Three additional sham-operated dogs served as neurally intact controls. Concentrations of label and glucose were measured in plasma. Regional myocardial deoxyglucose concentration was measured by quantitative autoradiography, following the calibration of plasma samples autoradiographic density by beta counting. Stimulation of right recurrent cardiopulmonary nerve afferent axons in the intact nervous system preparation did not significantly enhance deoxyglucose uptake as compared to neurally intact controls. When the right cervical vagosympathetic complex was cut a similar uptake was observed. Following decentralization of the right stellate ganglion, uptake was markedly reduced, as well as when the right cervical vagosympathetic was cut and the right stellate ganglion decentralized. CONCLUSIONS: Activation of afferent axons from cardiopulmonary receptors does not alter myocardial deoxyglucose uptake. Reduction in uptake occurs following unilateral stellate ganglion decentralization. PMID- 1463434 TI - [Energy intake of adult Great Danes]. AB - Energy intake and weight development were recorded in 5 adult Great Danes kept in outdoor kennels during maintenance, pregnancy and lactation. In periods with constant weights the energy requirement was 0.96 MJ DE/kg BW0.75/d with a minimum in summer (0.82) and a maximum in winter (1.1). In pregnancy (weight gain depending on litter size 7-15 kg) energy intake (ad-lib.-feeding) was similar to maintenance. During lactation energy intake reached 1.6-1.7 MJ DE/kg BW0.75/d with a dry matter intake of 83 g/kg BW0.75/d. Pups of great litters had to be fed with milk substitute for normal weight development. PMID- 1463435 TI - [Ionized calcium and total calcium in the blood of cattle, sheep, swine and horses of different ages, reproductive stages and uses]. AB - Concentrations of ionized calcium (Cai) in blood and of total calcium (Ca(t)) in serum were determined in 99 cattle, 58 sheep, 74 pigs and 59 horses of different age groups and reproductive periods as well as kinds of use of the animals. The values of Cai in blood in the groups taken into account for comparison of species decreased significantly in the order dairy cows < ewes < sows < horses. In cattle and pigs, there were significant differences in the Cai-level, according to age with the youngest animals having the highest values. In cows from the fourth lactation onward, one day post partum (p.p.) the smallest concentrations were measured, differing significantly from animals in other reproductive periods. In ewes, the lowest values were estimated one week before parturition. The level of Cai in blood of sows decreased between day one and 6 weeks p.p. significantly. No significant differences could be demonstrated between the different groups of horses. With regard to the concentrations of total Ca, differences between the groups were not so clear as with Cai. PMID- 1463436 TI - [Seroepidemiological studies on the detection of Q fever in sheep in middle Thuringia]. AB - In a random samples test altogether 4337 sheep of varying ages from several herds of different sizes in the middle region of Thuringia were investigated with complement fixing test for the existence of Q fever. In 47.1 per cent of the tested herds and in 5 from 8 of the included districts Q fever reagents were provable. The serological detection quota of all tested sheep amounts to 1.11 per cent, but the percentage of serological reagents in mother-sheep was 1.36 per cent, in the female young sheep 1.04 per cent and in the lambs 0.74 per cent. The investigations of rams and sheep for slaughter were negative. Serological testing in 7 sheep showed a Q fever antibody persistence about 6 until 10 months. Increased animal concentration and adverse conditions led to an increase of the Q fever seroprevalence in the herds. PMID- 1463437 TI - [Dog slaughtering in Germany in the 19th and 20th centuries with special consideration of the Munich area]. AB - In the 19th century professional dog slaughter and also the public sale of dog flesh arose. These slaughter and the sale was mainly practised by horse butchers. In Germany dogs had been mostly slaughtered in Sachsen, Schlesien, Anhalt and Bayern. From 1905 to 1940 the meat of 235.144 dogs was inspected. But the true number of slaughtered dogs was certainly larger. Yet in the fifties dogs were professionally slaughtered. After 1960 the slaughter dropped. Sporadically dog flesh was used as human food until 1985. The annual number of slaughtered dogs depended on economic factors like wages, prices of meat, availability of meat and dog tax. Dogs had been also slaughtered to produce dog fat for remedy. Slaughter of dogs has been already discussed in the 19th century. After 1930 it was called for abolishing the inspection order for dogs or for the prohibition of dog slaughter. After four bills of the years 1954, 1963 and 1985 the slaughter of dogs to produce human food was finally prohibited in 1986. PMID- 1463438 TI - [Tenacity of S. gallinarum in chicken feces]. AB - The survival period of 22 S. gallinarum strains in chicken feces was examined. The suspension of the bacterium was homogenized with a certain feces quantity. The initial ratio was 10(7) to 10(9) colony forming units per gram of feces. The results show that the growth of 5 strains was completely inhibited within 24 hours post homogenization, 7 strains were still positive to S. gallinarum for 24 hours, 5 strains were positive for 48 hours and the last 5 strains were positive for 4 days. Additionally, the effect of tryptose soy (TSB) and Rappaport Vassiliadis (RV) nutrient broths on the isolation rate of S. gallinarum from feces was examined at 37 degrees C and 43 degrees C. It was shown that the TSB medium was the best at 37 degrees C, in this experiment. The S. gallinarum concentration in RV medium was decreased at 37 degrees C from 9.1 x 10(8) to 1.6 x 10(6) and at 43 degrees C from 9.1 x 10(8) to 4.1 x 10(2). PMID- 1463439 TI - [The synchronization of sow parturition using a combined treatment regimen of cloprostenol Jenapharm and depotocin Spofa]. AB - The trials were conducted on a pig farm (German Landrace) over a period of about two years. This farm worked in 7-day cycles using artificial insemination. In trial 1, 209 sows were treated with the prostaglandin F2 alpha analog Cloprostenol (Cloprostenol Jenapharm, 87.5 micrograms i.m.). In trial 2, 646 sows were divided into two groups. Both groups were treated with 100 micrograms Cloprostenol Jenapharm not earlier than on the 113th day of gestation (day 1 of gestation = the day after the first insemination). 24 h later, 119 sows received an additional injection of 1 ml of an oxytocin analog (Depotocin inj. Spofa, 1 ml contains 0.2 mg Carbetocin). In the other group, 120 sows received 2 ml Depotocin. This additional treatment with Depotocin resulted in a mean interval from the injection to the onset of farrowing of 125 minutes (gilts) and 49 minutes (sows). In trial 2, 97.9% of the sows farrowed within 30 hours after Cloprostenol injection (= partus rate 30). The additional treatment with Depotocin resulted in a shortening of farrowing periods, a reduction in mean expulsion time and effected an increase in farrowing during the day time. All these effects were significant (p < or = 0.05). PMID- 1463440 TI - Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant. AB - Uptake of oxidatively modified low-density lipoprotein (LDL) by cells in the arterial wall is believed to be an important early event in the development of atherosclerosis. Because vitamin E is the major antioxidant present in human lipoproteins, it has received much attention as a suppressor of LDL lipid oxidation and as an epidemiological marker for ischaemic heart disease. However, a careful examination of lipid peroxidation in LDL induced by a steady flux of aqueous peroxyl radicals has demonstrated that, following consumption of endogenous ubiquinol-10, the rate of peroxidation (i) declines as vitamin E is consumed, (ii) is faster in the presence of vitamin E than following its complete consumption, (iii) is substantially accelerated by enrichment of the vitamin in LDL, either in vitro or by diet, and (iv) is virtually independent of the applied radical flux. We propose that perodixation is propagated within lipoprotein particles by reaction of the vitamin E radical (i.e. alpha-tocopheroxyl radical) with polyunsaturated fatty acid moieties in the lipid. This lipid peroxidation mechanism, which can readily be rationalized by the known chemistry of the alpha tocopheroxyl radical and by the radical-isolating properties of fine emulsions such as LDL, explains how reagents which reduce the alpha-tocopheroxyl radical (i.e. vitamin C and ubiquinol-10) strongly inhibit lipid peroxidation in vitamin E-containing LDL. PMID- 1463441 TI - Photoaffinity labelling of steroid-hormone-binding glutathione S-transferases with [3H]methyltrienolone. Inhibition of steroid-binding activity by the anticarcinogen indole-3-carbinol. AB - The identification and characterization of steroid-hormone-binding glutathione S transferases (GST) were undertaken using photoaffinity-labelling techniques. Irradiation of mouse liver cytosol, in the presence of 50 nM [3H]methyltrienolone, resulted in the specific affinity labelling of five proteins. One of these proteins, designated MBP27, had an approximate molecular mass of 27 kDa under denaturing conditions and was induced by treatment of mice with either 2(3)-t-butyl-4-hydroxyanisole (BHA) or phenobarbital (PB). An additional affinity-labelled protein, MBP25, which was not detected in untreated mouse cytosol, was induced in the liver cytosols from BHA- and PB-treated mice. The molecular masses of these proteins and their induction by BHA and PB suggested that they may be steroid-hormone-binding GST subunits. Irradiation of mouse liver cytosol in the presence of [3H]methyltrienolone, followed by immunoprecipitation using GST-specific antibodies established that both GST mu and GST alpha bind [3H]methyltrienolone and both contribute to the affinity labelled protein designated MBP27. GST Ya1 Ya1, an alpha class GST that is not expressed in untreated mouse liver but is induced by BHA and PB, was also found to bind [3H]methyltrienolone and is identical with the affinity-labelled protein designated MBP25. Experiments were undertaken next to assess the effects of the anticarcinogenic plant compound indole-3-carbinol (I3C) on GST-mediated steroid hormone-binding using the photoaffinity labelling techniques. Treatment of mice with I3C resulted in the induction of immunoreactive GST mu and GST Ya1 Ya1. However, the steroid-binding activity of these proteins in vitro was severely inhibited by the acid-condensation products of I3C that are generated in the stomach after ingestion. These results suggest that I3C may inhibit GST-mediated steroid-binding activity which could contribute to the anticarcinogenic activity of this compound. PMID- 1463442 TI - Regulation of pyruvate dehydrogenase kinase activity from pig kidney cortex. AB - The activity of pyruvate dehydrogenase (PDH) kinase in the purified PDH complex from pig kidney is sensitive to changes in ionic strength. The enzyme has optimum activity within a small range of ionic strength (0.03-0.05 M). An increase in ionic strength from 0.04 M to 0.2 M lowers the activity of PDH kinase by 32% and decreases the Km for ATP from 25 microM to 10 microM. At constant ionic strength (0.15 M) the enzyme has optimum activity over a broad pH range (7.2-8.0). The PDH kinase is stimulated 2.2-fold by 20 mM-K+, whereas Na+ even at high concentration (80 mM) has no effect on the enzyme activity. The stimulation of PDH kinase by K+ is not dependent on pH and ionic strength. PDH kinase is inhibited by HPO4(2-) in the presence of K+, whereas HPO4(2-) has no effect on the activity of this enzyme in the absence of K+. HPO4(2-) at concentrations of 2 and 10 mM inhibits PDH kinase by 28% and 55% respectively. The magnitude of this inhibition is not dependent on the ATP/ADP ratio. Inhibition by HPO4(2-) in the concentration range 0-10 mM is non-competitive with respect to ATP, and becomes mixed-type at concentrations over 10 mM. The Ki for HPO4(2-) is 10 mM. When HPO4(2-) is replaced by SO4(2-), the same effects on the activity of PDH kinase are observed. PDH kinase is also inhibited by Cl-. In the presence of 80 mM-Cl- the PDH kinase is inhibited by 40%. The inhibition by Cl- is not dependent on K+. In conclusion, we postulate that changes in phosphate concentrations may play a significant role in the regulation of PDH kinase activity in vivo. PMID- 1463443 TI - Purification and properties of oestradiol 17 beta-dehydrogenase extracted from cytoplasmic vesicles of porcine endometrial cells. AB - Porcine endometrial oestradiol-17 beta dehydrogenase was solubilized from the particulate fraction of homogenates sedimenting between 1200 g and 10,000 g by treatment with 0.4% Brij 35 in neutral buffers. The extracts were processed by successive passage through DEAE-Sepharose, Amberlyte XAD-2 and Blue-Sepharose, and the enzyme was collected from the washed affinity matrix at 0.8 M of a 0-2 M KCl gradient. A genuine oestrone reductase was eluted at 1.9 M-KCl. The dehydrogenase pool was resolved by butyl-Sepharose chromatography into a major (80%) peak (EDHM) eluted at 0.8 M-(NH4)2SO4 and a very hydrophobic fraction (VHF) recovered at 0.1 M. EDHM was further purified by filtration through Sephadex G 200 and cation-exchange chromatography on Mono S. Sephacryl 300 was used for VHF followed by Mono S. Enrichments from the homogenate amounted to 1074-fold for EDHM and 632-fold for VHF. A single silver-stained band at 32 kDa is seen on SDS/PAGE of EDHM, and VHF contains additional bands at 45 and 80 kDa. Polyclonal antibodies (G436) raised against EDHM and the monoclonal antibody F1 raised against VHF recognize the single 32 kDa band in EDHM and both the 32 kDa and 80 kDa bands in composite VHF. The 45 kDa band of VHF reacts with neither. Monoclonal antibody W1 raised against EDHM only recognizes the 32 kDa peptide of EDHM and VHF. The specific activity for oestradiol oxidation amounts to 4081 mu units/mg for EDHM and to 2402 mu-units/mg for VHF. Both possess a minimal (1/260) endogenous reductase activity and are devoid of 3 beta, 3 alpha- and 20 alpha dehydrogenases. We consider EDHM to be authentic oestradiol-17 beta dehydrogenase of porcine endometrium. The composite VHF could reflect the situation of the enzyme in vivo or result from aggregations occurring during processing. PMID- 1463444 TI - A competitive inhibitor of phospholipase A2 decreases surfactant phosphatidylcholine degradation by the rat lung. AB - We have shown previously that radiolabelled phosphatidylcholine (PC) in liposomes or natural surfactant is removed from the alveolar space and metabolically recycled in a process that is stimulated by cyclic AMP (cAMP). In this study, we evaluated the effect of a transition-state phospholipid analogue (MJ33; 1 hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol) that competitively inhibited acidic phospholipase A2 (PLA2) activity (pH 4.0) of lung homogenate by more than 97%, but had no effect on PLA2 activity at pH 8.5. MJ33 incorporated into unilamellar liposomes (dipalmitoyl PC/egg PC/cholesterol/phosphatidylglycerol, molar proportions 10:5:3:2) or co-sonicated with biosynthesized natural surfactant was instilled into the trachea of the anaesthetized rat; lungs were then removed for 2 h perfusion in the absence or presence of 0.1 mM-8-bromo cAMP. Total uptake for phospholipid was unchanged in the presence of the inhibitor MJ33. Degradation of labelled PC during 2 h perfusion in the absence of MJ33 was approx. 26% of that instilled for choline labelled liposomal PC, 16% for liposomal PC labelled in the second fatty-acyl position, and 33% for choline-labelled natural surfactant. Degradation of PC was decreased by approx. 25-40% for each substrate in the presence of MJ33. Inhibition of lipid degradation depended on the mole fraction of MJ33 in the liposomes and was maximal at 1 mol%. These studies demonstrate a significant role for acidic Ca(2+)-independent PLA2 in the degradation of internalized alveolar PC, but further indicate that this enzyme accounts for a minor fraction of total lung PC metabolism. PMID- 1463446 TI - Protein stability and interaction of the nicotinic acetylcholine receptor with cholinergic ligands studied by Fourier-transform infrared spectroscopy. AB - Based on the conformational dependence of the amide-I i.r. band, this paper explores the use of Fourier-transform i.r. spectroscopy methods to probe structural features of proteins present in native membranes from Torpedo highly enriched in acetylcholine receptor (AcChR). The interference of water absorbance on the amide-I spectral region has been eliminated through isotopic exchange by freeze-drying the membranes in the presence of trehalose to avoid protein denaturation induced by drying, followed by resuspension in deuterated water. AcChR-rich membrane samples prepared in such a way maintained an ability to undergo affinity-state transitions and to promote cation translocation in response to cholinergic agonists, which are functional characteristics of native untreated samples. The temperature-dependence of the i.r. spectrum indicates a massive loss of ordered protein structure, occurring at temperatures similar to those reported for thermal denaturation of the AcChR by differential scanning calorimetry and by thermal inactivation of alpha-bungarotoxin-binding sites on the AcChR [Artigues, Villar, Ferragut & Gonzalez-Ros (1987) Arch. Biochem. Biophys. 258, 33-41], thus suggesting that the observed i.r. spectral changes correspond to alterations in the structure of the AcChR protein. Furthermore, the presence of detergents as well as cholinergic agonists and antagonists produces spectral changes that are also consistent with the alterations in AcChR protein structure expected from previous calorimetric studies. In contrast with the information obtained by calorimetry, i.r. spectroscopy allows the contribution of secondary structural changes to be distinguished from the overall change in protein structure. Thus prolonged exposure to cholinergic agonists, which drives the AcChR protein into the desensitized state, produces only negligible alterations in the amide-I band shape, but increases substantially the thermal stability of the protein. This suggests that rearrangements in the tertiary or quaternary structure of the protein are more likely to occur than extensive changes in secondary structure as a consequence of AcChR desensitization. PMID- 1463445 TI - Determination of the intracellular distribution and pool sizes of apolipoprotein B in rabbit liver. AB - We have investigated the intracellular distribution of apolipoprotein B (apo B) in rabbit liver by immunoblotting, radioimmunoassay (r.i.a.) and enzyme-linked immunoassay (e.l.i.s.a.). Apo B100 was detected in total microsomes, rough microsomes, smooth microsomes, trans-enriched Golgi and cis-enriched Golgi and membrane and cisternal-content subfractions prepared from these fractions. There was also evidence of degradation of apo B100 in the Golgi membrane fractions. The amount of apo B in the subcellular fractions detected by competitive r.i.a. or e.l.i.s.a. ranged from 1.5 micrograms/mg of protein in the rough endoplasmic reticulum to 13 micrograms/mg of protein in the trans-Golgi fraction. Using internal standards (NADPH-cytochrome c reductase for the endoplasmic reticulum and galactosyltransferase for the Golgi membranes) it was calculated that all the apo B of liver is recovered within the secretory compartment, with 63% of the total apo B in the endoplasmic reticulum and the remainder in the Golgi. When the subcellular fractions were separated into membranes and cisternal contents, 60%, 50%, 60% and 30% of the total apo B was recovered in the membrane of the rough microsomes, smooth microsomes, cis-Golgi and trans-Golgi respectively. Using competitive e.l.i.s.a. we found that the membrane-bound form of the apo B was exposed at the cytosolic surface of the intact subcellular fractions. These observations are consistent with a model for assembly of very-low-density lipoproteins (VLDL) in which newly synthesized apo B is incorporated into a membrane-bound pool and a lumenal pool. The membrane-bound pool not used for VLDL assembly may be degraded, possibly in the Golgi region. PMID- 1463447 TI - Dissociated effects of 2-deoxy-D-glucose on D-[2-3H]glucose and D-[5-3H]glucose conversion into 3HOH in rat erythrocytes. AB - When rat erythrocytes were preincubated with 2-deoxy-D-glucose, the generation of both 3H-labelled acidic metabolites and 3HOH from D-[5-3H]glucose, the total production of L-lactate, and the generation of 14CO2, 14C-labelled acidic metabolites and 14C-labelled lactate from D-[1-14C]glucose or D-[U-14C]glucose were all lower than in erythrocytes preincubated in the absence of a hexose or in the presence of 3-O-methyl-D-glucose. However, preincubation with 2-deoxy-D glucose failed to decrease the generation of 3H-labelled acidic metabolites and L [3-3H]lactate from D-[2-3H]glucose, while decreasing the production of 3HOH more severely from D-[2-3H]glucose than from D-[5-3H]glucose. This may be attributable not solely to inhibition of D-glucose phosphorylation by 2-deoxy-D-glucose and 2 deoxy-D-glucose 6-phosphate, but also to inhibition by 2-deoxy-D-glucose 6 phosphate of hexose 6-phosphate interconversion in the reaction catalysed by phosphoglucoisomerase, as also observed with the purified enzyme. The generation of 3HOH from D-[2-3H]glucose should therefore be considered as a tool to assess the efficiency of interconversion of hexose 6-phosphates in the reaction catalysed by phosphoglucoisomerase, rather than to estimate D-glucose phosphorylation rate. PMID- 1463448 TI - Uptake and accumulation of 1-methyl-4-phenylpyridinium by rat liver mitochondria measured using an ion-selective electrode. AB - The compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes selective destruction of nigrostriatal dopaminergic neurons in primates, giving rise to a condition resembling Parkinson's disease. The toxicity of MPTP is believed to be due to its metabolite 1-methyl-4-phenylpyridinium (MPP+). MPP+ is an inhibitor of mitochondrial respiration at the NADH-ubiquinone oxidoreductase site and this, together with its selective transport into dopaminergic nerve terminals, accounts for its neurotoxicity. In this paper an electrode selective for MPP+ was developed and used to measure the rate of uptake and the steady-state accumulation of MPP+ in rat liver mitochondria. The initial rates of MPP+ uptake were not saturable, confirming previous work that the transport of MPP+ is not carrier-mediated. The membrane potential of mitochondria respiring on succinate was decreased by MPP+ and the steady-state accumulation ratio of MPP+ did not come to equilibrium with the mitochondrial transmembrane potential gradient (delta psi). The effect of the cation exchanger tetraphenylboron (5 microM) was to increase the initial rate of MPP+ uptake by about 20-fold and the steady-state accumulation by about 2-fold. This suggests that there may be a mechanism of efflux of MPP+ from mitochondria which allows MPP+ to cycle across the membrane and thus decrease delta psi. These data indicate that MPP+ interacts with mitochondria independently of its inhibition of NADH-ubiquinone oxidoreductase, and these alternative interactions may be of relevance for its mechanism of neurotoxicity. PMID- 1463449 TI - Ethanol and glycogen synthesis in cardiothoracic and skeletal muscles following glucose re-feeding after starvation in the rat. AB - The pattern of glycogen deposition in individual cardiothoracic and skeletal muscles in response to oral and intraperitoneal glucose administration was examined in 40 h-starved rats. Rates of glycogen synthesis were consistently higher in oxidative muscles than in non-oxidative muscles. Intragastric ethanol administration was associated with an impaired glycaemic response and the almost total abolition of glycogen deposition in oxidative muscles in response to oral or intraperitoneal glucose re-feeding. This effect was dose-dependent and differential, in that ethanol produced no equivalent impairment in glycogen deposition in non-oxidative muscles. Ethanol treatment also selectively promoted glycogenolysis in oxidative muscles in the starved state. There was positive correlation (P < 0.001) between the decrease in glycogen levels in soleus and diaphragm muscles in response to increasing ethanol doses and blood glucose and lactate concentrations after intraperitoneal glucose administration, implying that the basis for the impairment in glycogen synthesis may be diminished glucose availability. The mechanism whereby ethanol may differentially compromise carbohydrate metabolism in oxidative muscles is discussed. PMID- 1463450 TI - A non-glycosylated extracellular superoxide dismutase variant. AB - The secretory tetrameric extracellular superoxide dismutase (EC-SOD) is the only glycosylated SOD isoenzyme. The importance of the carbohydrate moiety for the properties of the enzyme is unknown. An expression vector defining nonglycosylated EC-SOD (ngEC-SOD) was constructed by mutagenesis of the codon for Asn-89 into a codon for Gln. The vector was transfected into Chinese hamster ovary DXB-11 cells and ngEC-SOD was isolated to 70% purity from the culture media of selected clones. The absence of glycosylation was established by the lack of affinity for various lectins, the absence of staining with the periodic acid Schiff reagent, the change in mobility and composition of the tryptic peptide containing the mutated glycosylation site, and the reduction in apparent molecular mass upon SDS/PAGE and size-exclusion chromatography. The tetrameric state was retained. The heparin affinity, a fundamental and distinguishing property of EC-SOD, was found to be slightly increased. The enzymic activity was essentially retained. The major difference from native glycosylated enzyme in physical properties was a marked reduction in solubility. Like glycosylated EC SOD, ngEC-SOD was, after intravenous injection into rabbits, rapidly sequestered by the vessel endothelium, and was promptly released into plasma after injection of heparin. The only difference from glycosylated EC-SOD in this behaviour, was a slightly more rapid elimination of the mutant enzyme from the vasculature. It is concluded that no specific biological role for the EC-SOD carbohydrate moiety could be revealed. PMID- 1463451 TI - Ca2+ influx induced by the Ca(2+)-ATPase inhibitors 2,5-di-(t-butyl)-1,4 benzohydroquinone and thapsigargin in bovine adrenal chromaffin cells. AB - We have characterized the effect of the Ca(2+)-ATPase inhibitors 2,5-di-(t-butyl) 1,4-benzohydroquinone (tBHQ) and thapsigargin on the concentration of cytosolic Ca2+ in single bovine adrenal chromaffin cells by video-imaging of fura-2-loaded cells. Addition of either inhibitor released Ca2+ from internal stores in the absence of external Ca2+. tBHQ was unable to stimulate further Ca2+ release after addition of thapsigargin, but thapsigargin could do so after release by tBHQ, indicating that the tBHQ-sensitive stores are a sub-set of those sensitive to thapsigargin. Angiotensin II was able to elicit Ca2+ release after application of tBHQ, indicating that at least part of the tBHQ-sensitive stores were distinct from those discharged by Ins(1,4,5)P3. In the presence of external Ca2+, both Ca(2+)-ATPase inhibitors produced a more prolonged rise in cytosolic Ca2+ consistent with stimulated Ca2+ entry. The ability of the inhibitors to activate a Ca(2+)-entry pathway was confirmed by monitoring quenching of fura-2 after stimulated entry of the Ca2+ surrogate Mn2+. These findings indicate that bovine adrenal chromaffin cells possess a mechanism by which Ca2+ entry can be activated, following emptying of certain internal stores, independently of receptor occupation. PMID- 1463452 TI - Characterization of a phenobarbital-inducible cytochrome P-450, NADPH-cytochrome P-450 reductase and reconstituted cytochrome P-450 mono-oxygenase system from rat brain. Evidence for constitutive presence in rat and human brain. AB - Cytochrome P-450 was purified to apparent homogeneity from the brain microsomes of phenobarbital-treated rats. The specific content of the purified P-450 was 12.7 nmol/mg of protein. NADPH-cytochrome P-450 reductase (reductase) was also purified to apparent homogeneity from brain microsomes. The specific content was 34.7 mumol of cytochrome c reduced/min per mg of protein. The reduced carbon monoxide spectrum of purified P-450 exhibited a peak at 450 nm. Both the P-450 and the reductase moved as single bands on SDS/PAGE. The molecular masses of the purified P-450 and the reductase were determined to be 53.3 and 72.0 kDa respectively. The purified brain P-450 cross-reacted with antibodies to rat liver P-450IIB1/IIB2 when examined by Western immunoblotting, but no immunological similarity was observed with rat liver P-450IA1/IA2 or P-450IIE1. Purified rat brain reductase cross-reacted with antibodies to rat liver reductase. Further, immunoblot experiments with untreated rat and human brain microsomes using antisera to the purified rat brain P-450 and reductase indicated that these forms of P-450 and NADPH-cytochrome P-450 reductase exist constitutively in rat and human brain. Purified rat brain P-450 was reconstituted with purified NADPH cytochrome P-450 reductase, deoxycholate and dilauroyl glyceryl 3-phosphocholine. NADPH-dependent N-demethylation of aminopyrine and morphine was observed in the reconstituted system. The catalytic-centre activities were 80.25 and 38.2 nmol of formaldehyde formed/min per nmol of P-450 respectively. The reconstituted system had a comparatively lower catalytic-centre activity for 7-ethoxycoumarin O-de ethylase (10.5 nmol of product formed/min per nmol of P-450). PMID- 1463453 TI - D-myo-inositol 1,3,4,5-tetrakisphosphate releases Ca2+ from crude microsomes and enriched vesicular plasma membranes, but not from intracellular stores of permeabilized T-lymphocytes and monocytes. AB - In the human T-lymphocyte cell lines Jurkat and HPB.ALL and the human monocytoid cell line U937, Ins(1,3,4,5)P4 triggers a dose-dependent release of Ca2+ from crude microsomal preparations, with a half-maximal effective concentration (EC50) of 1.2-2.3 microM. Similar results were obtained with enriched vesicular plasma membranes from U937 cells. However, in permeabilized preparations of the same cell types only Ins(1,4,5)P3 was able to release Ca2+ from intracellular stores, with EC50 values in the range 0.11-0.84 microM. In crude microsomes the effects of Ins(1,3,4,5)P4 and Ins(2,4,5)P3, a non-metabolizable InsP3 isomer, occurred independently of each other, indicating subpopulations of Ins(1,3,4,5)P4- and Ins(1,4,5)P3-sensitive vesicles. The Ins(1,3,4,5)P4 preparation used for the Ca(2+)-release experiments contains neither Ca2+ nor contaminating Ins(1,4,5)P3 and was not metabolized to Ins(1,4,5)P3 during the Ca(2+)-release experiments. We conclude that Ins(1,3,4,5)P4 independently of Ins(1,4,5)P3 induces a Ca2+ flux via a membrane compartment, most likely the plasma membrane, that is functionally destroyed during the permeabilization of the cells. PMID- 1463454 TI - Regulation of S-adenosylmethionine decarboxylase activity by alterations in the intracellular polyamine content. AB - The effects of addition of exogenous spermidine and spermine and of two inhibitors of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), which decreases spermidine concentrations, and n-butyl-1,3-diaminopropane, which depletes spermine, on the expression of S-adenosylmethionine decarboxylase (AdoMetDC) activity were studied in mammalian cell lines (HT29, CHO and COS-7). AdoMetDC levels were inversely related to the polyamine content, and spermine was the more potent repressor of AdoMetDC activity, but only spermidine affected the amount of AdoMetDC mRNA. Transfection of COS-7 cells or CHO cells with plasmid constructs containing a chloramphenicol acetyltransferase (CAT) reporter gene driven by portions of the AdoMetDC promoter region indicated that CAT expression was altered by spermidine, but not by spermine, suggesting that there is a spermidine-responsive element in this promoter. Transient transfection of COS-7 cells with pSAMh1, a plasmid containing the AdoMetDC cDNA in a vector with the SV40 promoter and origin of replication, led to a large increase in AdoMetDC expression. Although treatment of COS-7 cells with n-butyl-1,3-diaminopropane greatly increased endogenous AdoMetDC activity, the spermine depletion brought about by this inhibitor did not stimulate AdoMetDC expression from pSAMh1. The pSAMh1 cDNA is missing 72 nucleotides from the 5' end of the AdoMetDC mRNA, and it is possible that translational regulation by spermine involves this region. The expression of AdoMetDC from pSAMh1 in COS-7 cells was greatly inhibited by DFMO treatment, although endogenous AdoMetDC activity was increased. The expression of other plasmids containing the SV40 origin of replication was also inhibited by DFMO in COS-7 cells, but not in CHO cells. DFMO treatment did not interfere with the expression of plasmids driven by the RSV promoter. These results suggest that low spermidine levels interfere with the replication of plasmids containing the SV40 origin of replication. PMID- 1463455 TI - Control of plasma-membrane Ca2+ entry by the intracellular Ca2+ stores. Kinetic evidence for a short-lived mediator. AB - We have studied the correlation between the degree of filling of the intracellular Ca2+ stores and the plasma-membrane permeability to Mn2+, a Ca2+ surrogate for plasma-membrane Ca2+ channels, in human neutrophils loaded with fura-2. Refilling of the stores of cells previously depleted of Ca2+ decreased the entry of Mn2+, but the magnitude of this effect depended on the refilling protocol. When refilling was allowed to proceed to steady-state levels by a 3 min incubation with different external Ca2+ concentrations (0.05-1 mM), almost complete inhibition of Mn2+ entry was observed at 40% of maximum refilling. In contrast, when different degrees of store refilling were attained by incubation with 1 mM-Ca2+ for short periods (10-40 s), inhibition of Mn2+ entry was smaller at comparable degrees of refilling. When quick refilling was allowed to proceed up to 40% (about 20 s at 37 degrees C) and then stopped at this level by removal of external Ca2+, the rate of Mn2+ uptake was high just after refilling and then decreased with time within the next few seconds (half-times approximately 7 s at 37 degrees C and approximately 20 s at 25 degrees C). We have proposed previously that the Ca2+ stores, when emptied of Ca2+, may generate a second messenger able to open the plasma-membrane Ca2+ channels by a mechanism involving cytochrome P 450. The results here are consistent with the existence of such a messenger and suggest that it is cleared from the cytoplasm with a half-time of about 7 s at 37 degrees C. In addition, inhibition of Mn2+ entry in cells with empty Ca2+ stores by cytochrome P-450 inhibitors showed a time lag consistent with the clearance kinetics proposed above. PMID- 1463456 TI - Analysis of algebraic weighted least-squares estimators for enzyme parameters. AB - An algorithm for the least-squares estimation of enzyme parameters Km and Vmax. is proposed and its performance analysed. The problem is non-linear, but the algorithm is algebraic and does not require initial parameter estimates. On a spreadsheet program such as MINITAB, it may be coded in as few as ten instructions. The algorithm derives an intermediate estimate of Km and Vmax. appropriate to data with a constant coefficient of variation and then applies a single reweighting. Its performance using simulated data with a variety of error structures is compared with that of the classical reciprocal transforms and to both appropriately and inappropriately weighted direct least-squares estimators. Three approaches to estimating the standard errors of the parameter estimates are discussed, and one suitable for spreadsheet implementation is illustrated. PMID- 1463457 TI - A cDNA clone for human glucosamine-6-sulphatase reveals differences between arylsulphatases and non-arylsulphatases. AB - Glucosamine-6-sulphatase is an exo-hydrolase required for the lysosomal degradation of heparan sulphate and keratan sulphate. Deficiency of glucosamine-6 sulphatase activity leads to the lysosomal storage of the glycosaminoglycan, heparan sulphate and the monosaccharide sulphate N-acetylglucosamine 6-sulphate and the autosomal recessive genetic disorder mucopolysaccharidosis type IIID. Glucosamine-6-sulphatase can be classified as a non-arylsulphatase since, relative to arylsulphatase B, it shows negligible activity toward 4 methylumbelliferyl sulphate. We have isolated human cDNA clones and derived amino acid sequence coding for the entire glucosamine-6-sulphatase protein. The predicted sequence has 552 amino acids with a leader peptide of 36 amino acids and contains 13 potential N-glycosylation sites, of which it is likely that 10 are used. Glucosamine-6-sulphatase shows strong sequence similarity to other sulphatases such as the family of arylsulphatases, although the degree of similarity is not as high as that between members of the arylsulphatase family. This pattern of inter- and intra-family similarity delineates regions and amino acid residues that may be critical for sulphatase function and substrate specificity. PMID- 1463458 TI - Erythroid expression and DNAaseI-hypersensitive sites of the carbonic anhydrase 1 gene. AB - The carbonic anhydrase 1 gene is expressed in adult human and mouse erythroid cells and colon epithelia from two distinct promoters. We have explored the erythroid promoter for cis-acting sequences involved in transcription using DNAaseI as a probe. Two DNAaseI-hypersensitive sites (DHS-1 and DHS-2) have been identified in the distal erythroid promoter in CA1-expressing erythroleukaemic cells. These sites are present at low levels in K562 cells, which have a foetal/embryonic phenotype and do not express CA1. DHS-1 and DHS-2 are not present in non-erythroid cells, including colon cells, which express CA1 from the proximal colon promoter. DHS-1 and DHS-2 were also generated in an heterologous CA1 gene containing 5 kb of erythroid promoter sequence after transfection into erythroid cells, including K562 cells. These transfection studies showed that both this fragment, and an abbreviated 817 bp promoter fragment which contains only DHS-1, were sufficient to confer erythroid-specific expression to a reporter gene. These promoters were active in cell lines expressing CA1 and in K562 cells. This latter observation implies that a developmental repressor factor is both present in K562 cells and binds to a cis-acting sequence that is absent from the sequence 5 kb upstream of the erythroid transcription start site. PMID- 1463459 TI - Characterization of a human seminal plasma glycosaminoglycan-bearing polypeptide. AB - A glycosaminoglycan-bearing polypeptide (S.GP), present in human seminal plasma, was purified to homogeneity by a combination of CsCl density-gradient centrifugation, f.p.l.c. ion-exchange chromatography on a Mono Q HR column and Superose 6 gel filtration. The observed polydispersity of S.GP was attributed to the heterogeneity of its glycosaminoglycan content. Enzymic deglycosylation experiments and N-terminal amino-acid sequence determination indicate that it consists of a polypeptide (apparent molecular mass approx. 18 kDa) bearing both chondroitin and heparan sulphate chains. Evidence is given that S.GP contains a glycosaminoglycan-linkage domain of a so far uncharacterized gene product, proteolytically processed in the genital tract. PMID- 1463460 TI - Active-site characterization of S1 nuclease. II. Involvement of histidine in catalysis. AB - Modification of the histidine residues of purified S1 nuclease resulted in loss of its single-stranded (ss)DNAase, RNAase and phosphomonoesterase activities. Kinetics of inactivation indicated the involvement of a single histidine residue in the catalytic activity of the enzyme. Furthermore, histidine modification was accompanied by the concomitant loss of all the activities of the enzyme, indicating the presence of a common catalytic site responsible for the hydrolysis of ssDNA, RNA and 3'-AMP. Substrate protection was not observed against Methylene Blue- and diethyl pyrocarbonate (DEP)-mediated inactivation. The histidine (DEP) modified enzyme could effectively bind 5'-AMP, a competitive inhibitor of S1 nuclease, whereas the lysine (2,4,6-trinitrobenzenesulphonic acid)-modified enzyme showed a significant decrease in its ability to bind 5'-AMP. The inability of the substrates to protect the enzyme against DEP-mediated inactivation, coupled with the ability of the modified enzyme to bind 5'-AMP effectively, suggests the involvement of histidine in catalysis. PMID- 1463461 TI - Synthesis of 35S-labelled macromolecules by polymorphonuclear neutrophils. Evidence for the production of [35S]sulphite which can modify both endogenous and exogenous proteins. AB - The incorporation of [35S]sulphate into macromolecules by rabbit peritoneal polymorphonuclear neutrophils (PMN) in vitro revealed that two major groups of 35S-labelled macromolecules were synthesized by these cells. The first group did not bind to anion-exchange columns at pH 6.0 and contained 60-80% of the total incorporated radiolabel. The second group did bind to anion-exchange columns at pH 6.0 and eluted as a single peak of radioactivity at an ionic strength characteristic of sulphated proteoglycans; it accounted for the remaining incorporated radiolabel. Analysis of this material on Sepharose CL-6B demonstrated that 35S-labelled macromolecules isolated from the cell extract migrated with Kav. of 0.36, while corresponding material isolated from the medium migrated with Kav. of 0.51. When subjected to electrophoresis on SDS/polyacrylamide gels the intact proteoglycan had a molecular mass of approx. 90 kDa and yielded two core proteins of molecular mass 31 kDa and 28 kDa after digestion with chondroitinase ABC. The peak of labelled macromolecules which did not bind to the anion-exchange column was found, by SDS/PAGE, to comprise 35S labelled proteins of various molecular masses. The 35S label was displaced from this fraction by treatment with 0.1 M-sodium sulphite, suggesting that the radiolabel was in the form of an S-sulpho sulphite derivative. Using the sulphite trapping agents N-2,4-dinitroanilinomaleimide and cyst(e)ine, [35S]sulphite was detected in the incubation medium of PMN, indicating that these cells were able to synthesize [35S]sulphite from [35S]sulphate. The release of [35S]sulphite from neutrophil cultures was calculated to be 78 pmol/h per 10(6) cells. When exogenous proteins were included in the incubation medium of cell cultures, the [35S]sulphite reacted with these proteins to form a stable 35S-labelled conjugate. PMID- 1463462 TI - Increased gall-bladder prostanoid synthesis after bile-duct ligation in the rabbit is secondary to new enzyme formation. AB - Ligation of the common bile duct (BDL) in the male rabbit resulted in increased gall-bladder microsomal total cyclo-oxygenase activity with prostaglandin E2 (PGE2) and 6-oxoprostaglandin F1 alpha [6-oxo-PGF1 alpha, stable metabolite of prostaglandin I2 (PGI2; prostacyclin)] as the major prostanoids synthesized after 24 and 72 h. Kinetic analysis of gallbladder microsomal membrane fractions incubated with increasing levels of [14C]arachidonic acid indicated that BDL for 24 and 72 h did not change substrate affinity (apparent Km) but markedly increased the rate of conversion (apparent Vmax.) suggesting the presence of more total enzyme responsible for synthesis of 6-oxo-PGF1 alpha and PGE2. BDL for 24 and 72 h significantly increased gall-bladder tissue slice basal release of 6-oxo PGF1 alpha, but not PGE2, when compared with the controls. Gall-bladder slice release of PGE2 was 3-fold less than 6-oxo-PGF1 alpha in the control gall-bladder slices. Immunoblot analysis of 72 h BDL gall-bladder microsomal membrane fractions showed a slight increase in cyclo-oxygenase content and a 5-fold increase in the content of prostacyclin synthase as compared with the control. These data suggest that the BDL-stimulated total gall-bladder cyclo-oxygenase activity was the result of an increase in the level of specific prostaglandin synthetic enzymes, in particular prostacyclin synthase, and not from a change in enzyme affinity. PMID- 1463463 TI - Evidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin. AB - The ability to incorporate iron in vitro was studied in homopolymers of human ferritin L-chain, human ferritin H-chain and its variants and in homopolymer mixtures. The H-chain variants carried amino acid substitutions in the ferroxidase centre and/or in carboxy residues on the cavity surface. Iron incorporation was examined by gel electrophoresis of the reaction products by staining for iron and protein. It was found that inactivation of the ferroxidase centre combined with the substitution of four carboxy groups on the cavity abolished the ability of H-chain ferritin to incorporate iron. Competition experiments with limited amounts of iron showed that, at neutral pH, L-chain ferritin is more efficient in forming iron cores than the H-chain variants altered at the ferroxidase activity or in the cavity. Competition experiments at pH 5.5 demonstrated that L-chain apoferritin is able to incorporate iron only when in the presence of H-chain variants with ferroxidase activity. The results indicate that L-chain apoferritin has a higher capacity than the H-chain apoferritin to induce iron-core nucleation, whereas H-chain ferritin is superior in promoting Fe(II) oxidation. The finding of cooperative roles of the H- and L chains in ferritin iron uptake provides a clue to understanding the biological function of isoferritins. PMID- 1463464 TI - Cell-mediated degradation of type IV collagen and gelatin films is dependent on the activation of matrix metalloproteinases. AB - The ability of normal rabbit dermal fibroblasts to degrade films of type IV collagen and gelatin when stimulated by phorbol ester was shown to be dependent on the induction, secretion and activation of 95 kDa gelatinase B and the secretion and activation of 72 kDa gelatinase A and stromelysin. Degradation was inhibited by exogenous human recombinant tissue inhibitor of metalloproteinases 1, specific antibodies to gelatinase and stromelysin and by the reactive-oxygen metabolite inhibitor catalase. We discuss the various pathways for activation of matrix metalloproteinases in this model system and conclude that, although plasmin may play a key role in the activation of gelatinase B and stromelysin, gelatinase A is activated by a mechanism which has yet to be elucidated. The involvement of oxygen radicals in the direct activation of matrix metalloproteinases in this model is thought to be unlikely. PMID- 1463465 TI - Demonstration of cathepsins B, H and L in xenografts of normal and Duchenne muscular-dystrophy muscles transplanted into nude mice. AB - The activities and contents of the lysosomal cysteine proteinases cathepsins B, H and L were examined in xenografts of biopsied muscles transplanted from age matched normal subjects and Duchenne-muscular-dystrophy (DMD) patients into nude mice. The activity of cathepsin B increased 9-fold and that of B-plus-L increased 24-fold in the first week after transplantation in normal muscle xenografts. By the third week, the activity of cathepsin B increased a total of 20-fold and B plus-L increased to 36-fold the original level. The activity levels of cathepsin B, B-plus-L, H and D, and acid phosphatase in normal and DMD xenografts were not significantly different when compared 2 weeks after transplantation. However, the protein content of cathepsin B in DMD muscle xenografts was more than 3-fold that of normal xenografts at 2 weeks. The profile of cathepsin H activity in normal muscle xenografts was different than those of cathepsins B and B-plus-L. In the first week, the cathepsin H diminished sharply to about one-third of the biopsied muscle level and then, by 3 weeks after transplantation, it had increased slightly to about half the original level. The amount of endogenous cysteine proteinase inhibitor changed in parallel with the activity of cathepsins B and B plus-L. Cathepsins B and H, but not cathepsin L, were found immunohistochemically in regenerating muscle fibres of normal and DMD xenografts 2 weeks after transplantation. Staining of cathepsin B in DMD xenografts was slightly stronger than that in normal subjects. There was no immunostaining in degenerating or necrotic muscle fibres 2 weeks after transplantation. Western-blot analysis revealed that the cathepsin B band at 29 kDa was increased in normal xenografts 2 and 3 weeks after transplantation. Also, 2 weeks after transplantation the staining intensity of this band was slightly stronger in DMD xenografts than in normal xenografts. These results suggest that cathepsin B participates in the regeneration of transplanted muscle, both normal and DMD, and in the DMD muscle fibre-wasting processes, during regeneration. PMID- 1463466 TI - Caeruloplasmin biosynthesis by the human uterus. AB - The blue copper protein caeruloplasmin is synthesized mainly by hepatocytes. An alternative transcript for caeruloplasmin produced in certain extrahepatic tissues, CP-1, contains an additional 12 nucleotides encoding 4 amino acids not present in the hepatic transcript, CP-2 [Yang, Friedrichs, Cupples, Bonifacio, S Sanford, Horton & Bowman (1990) J. Biol. Chem. 265, 10780-10785]. We have demonstrated transcription of caeruloplasmin mRNA by a well-differentiated human uterine epithelial adenocarcinoma cell line, Ishikawa, and by human uterine endometrium and purified endometrial glands. Identical CP-2 nucleotide sequences were obtained for partial caeruloplasmin transcripts from human liver and Ishikawa cells, indicating that CP-2 transcripts are produced by uterine epithelial lining cells. The synthesis of caeruloplasmin protein was demonstrated for Ishikawa cells and another uterine adenocarcinoma cell line, ECC1. Peptide mapping analysis indicated that caeruloplasmin secreted by Ishikawa cells was structurally identical with the protein synthesized by the human hepatoblastoma cell line HepG2. The secretion of a 135,000-M(r) caeruloplasmin by Ishikawa and ECC1 cells, comparable with that of the human hepatoblastoma cell line, HepG2, indicated similar processing of uterine and hepatic caeruloplasmin. Incorporation of 67Cu into caeruloplasmin was demonstrated for Ishikawa and ECC1 cells, suggesting that the human uterus produces a bioactive form of caeruloplasmin and possesses the necessary metal transporters and intracellular machinery for copper incorporation into this protein. PMID- 1463467 TI - Possible multifunction of glucose transporter. Transport of nicotinamide by reconstituted liposomes. AB - A kinetic study of the uptake of nicotinamide by reconstituted liposomes containing the human erythrocyte glucose transporter, compared with that of D glucose, demonstrated that the Km and Vmax. values were almost the same for each compound, and that the uptake of D-glucose was competitively inhibited by nicotinamide. At 20 mM concentration, 2-deoxy-D-glucose, 3-O-methyl-D-glucose and 4,6-O-ethylidene-D-glucose all caused 50% inhibition of nicotinamide uptake, but L-glucose and nicotinic acid were not inhibitory. Similar results were obtained for the uptake of D-glucose. Cytochalasin B binding to the liposomes was inhibited in a dose-dependent manner by either nicotinamide or D-glucose. Antibody for glucose transporter detected in band 4.5 by SDS/PAGE inhibited the uptake of D-glucose and nicotinamide. A possible uptake of nicotinamide by nucleoside transporter was excluded. In human erythrocytes, cytochalasin B binding was inhibited dose-dependently by either nicotinamide or D-glucose, and cytochalasin B depressed the uptake of both nicotinamide and 2-deoxy-D-glucose. These findings were well reproduced in the reconstituted liposomes. The very close similarities between uptake of nicotinamide and D-glucose suggest that the glucose transporter plays a direct role in transport of nicotinamide, which is structurally quite different from monosaccharides, and thus that the transporter is probably multifunctional. PMID- 1463468 TI - Evidence that GLUT-2 mRNA and protein concentrations are decreased by hyperinsulinaemia and increased by hyperglycaemia in liver of diabetic rats. AB - GLUT-2, glucokinase (GK) and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was studied in the liver of chronically catheterized diabetic rats during the 3 days after an intravenous injection of 65 mg of streptozotocin (STZ)/kg. At 6 h after the STZ injection, portal plasma insulin levels were 270 +/- 32 mu-units/ml and blood glucose was 1.4 +/- 0.4 mmol/l, owing to pancreatic beta-cell destruction. GLUT-2 and PEPCK mRNA concentrations were rapidly and dramatically decreased (> 90%), whereas GK mRNA was increased. After 30 h, plasma insulin concentrations were lower than 5 mu-units/ml and blood glucose was > 20 mmol/l. GLUT-2 and PEPCK mRNA concentrations increased 2-fold and GK mRNA disappeared progressively. In order to assess the relative roles of hyperglycaemia and insulinopenia, blood glucose was clamped at 6.4 +/- 0.5 mmol/l from 18 to 72 h after STZ injection by phlorizin infusion (0.5-2 g/day per kg) or at 6.6 +/- 0.3 mmol/l from 18 to 48 h after STZ injection by insulin infusion (0.25 unit/min per kg). GLUT-2 mRNA concentrations were 50% lower in phlorizin infused than in untreated diabetic rats. The low levels of GK mRNA and the high levels of PEPCK mRNA were unaffected by normalization of hyperglycaemia in phlorizin-infused diabetic rats. In insulin-infused rats (portal plasma insulin levels of 40 mu-units/ml) GLUT-2 mRNA levels were 25% of those in untreated diabetic rats, and they increased rapidly 6 h after insulin infusion was stopped. Liver GLUT-2 protein concentration showed similar changes in response to STZ injection and to phlorizin or insulin treatment, but after a delay of several hours. From this work we conclude that GLUT-2 gene expression is dramatically and rapidly (< 6 h) decreased by portal hyperinsulinaemia and increased by hyperglycaemia. PMID- 1463469 TI - Cell volume and bile acid excretion. AB - The interaction between cell volume and taurocholate excretion into bile was studied in isolated perfused rat liver. Cell swelling due to hypo-osmotic exposure, addition of amino acids or insulin stimulated taurocholate excretion into bile and bile flow, whereas hyperosmotic cell shrinkage inhibited these. These effects were explained by changes in Vmax of taurocholate excretion into bile: Vmax. increased from about 300 to 700 nmol/min per g after cell swelling by 12-15% caused by either hypo-osmotic exposure or addition of amino acids under normo-osmotic conditions. Steady-state taurocholate excretion into bile was not affected when the influent K+ concentration was increased from 6 to 46 mM or decreased to 1 mM with iso-osmoticity being maintained by corresponding changes in the influent Na+ concentration. Replacement of 40 mM-NaCl by 80 mM-sucrose decreased taurocholate excretion into bile by about 70%; subsequent hypo-osmotic exposure by omission of sucrose increased taurocholate excretion to 160%. Only minor, statistically insignificant, effects of aniso-osmotic cell volume changes on the appearance of bolus-injected horseradish peroxidase in bile were observed. Taurocholate (400 microM) exhibited a cholestatic effect during hyperosmotic cell shrinkage, but not during hypo-osmotic cell swelling. Both taurocholate and tauroursodeoxycholate increased liver cell volume. Tauroursodeoxycholate stimulated taurocholate (100 microM) excretion into bile. This stimulatory effect was strongly dependent on the extent of tauroursodeoxycholate-induced cell swelling. During continuous infusion of taurocholate (100 microM) further addition of tauroursodeoxycholate at concentrations of 20, 50 and 100 microM increased cell volume by 10, 8 and 2% respectively, in parallel with a stimulation of taurocholate excretion into bile by 29, 27 and 9% respectively. There was a close relationship between the extent of cell volume changes and taurocholate excretion into bile, regardless of whether cell volume was modified by tauroursodeoxycholate, amino acids or aniso-osmotic exposure. The data suggest that: (i) liver cell volume is one important factor determining bile flow and biliary taurocholate excretion; (ii) swelling-induced stimulation of taurocholate excretion into bile is probably not explained by alterations of the membrane potential; (iii) bile acids modulate liver cell volume; (iv) taurocholate-induced cholestasis may depend on cell volume; (v) stimulation of taurocholate excretion into bile by tauroursodeoxycholate can largely be explained by tauroursodeoxycholate-induced cell swelling. PMID- 1463470 TI - Escherichia coli dihydrodipicolinate synthase. Identification of the active site and crystallization. AB - Escherichia coli dihydrodipicolinate synthase (DHDPS) (EC 4.2.1.52), the first enzyme unique to lysine biosynthesis, catalyses the condensation of pyruvate and aspartate beta-semialdehyde (ASA) by a ping-pong mechanism. Pyruvate binds first to the enzyme, forming a Schiff base with the epsilon-amino group of Lys-161, followed by binding of ASA. Km values of 0.57 and 0.55 mM were determined for pyruvate and DL-ASA respectively. 3-Bromopyruvate inhibits DHDPS with a Ki of 1.6 mM. DHDPS is 50% inhibited by 1.0 mM-L-lysine, 1.2 mM-sodium dipicolinate or 4.6 mM-S-2-aminoethyl-L-cysteine. Crystals of DHDPS diffracting to beyond a resolution of 0.24 nm (2.4 A) were obtained under several experimental conditions. Diffraction patterns were compatible with trigonal space groups P3(1)21 or P3(2)21, with unit-cell parameters a = b = 12.26 nm and c = 11.19 nm. The density of the crystals indicates the presence of a dimer of DHDPS subunits per asymmetric unit. PMID- 1463471 TI - NIH conference. Gastrointestinal infections in AIDS. AB - As the largest lymphoid organ in the body, the gastrointestinal tract is a potential reservoir for human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), and it is an important site for HIV-induced immunodeficiency. The resulting defects in cellular and humoral defense mechanisms predispose the gastrointestinal tract to a spectrum of viral, fungal, bacterial, and protozoan pathogens that cause relentless morbidity and, in some cases, death. With a thorough diagnostic evaluation, physicians can identify one or more of these pathogens in a majority of patients with AIDS who have gastrointestinal symptoms. The identification of enteric pathogens in patients with AIDS is important because an increasing array of therapeutic regimens is becoming available to treat many of these infections. PMID- 1463472 TI - Pigmented villonodular synovitis of the knee. The results of total arthroscopic synovectomy, partial, arthroscopic synovectomy, and arthroscopic local excision. AB - Twenty-five patients who had had a diagnosis of pigmented villonodular synovitis of the knee were followed for an average of four and one-half years (range, two to ten years) after arthroscopic treatment. Five patients had had localized lesions and had been managed with local resection; all five had improvement, with no apparent recurrence. The remaining twenty patients had had diffuse disease. Of these twenty, eleven had had a complete arthroscopic synovectomy. All eleven had definite improvement in pain and function, and almost all had a decrease in synovitis and an increase in the range of motion of the knee; the disease recurred in only one. The other nine patients had had a partial arthroscopic synovectomy. Although most had some improvement in function and range of motion and a decrease in pain and synovitis, the disease recurred in five of the nine. Thus, in the patients who had had diffuse pigmented villonodular synovitis, the rate of recurrence was lower in those who had had a complete arthroscopic synovectomy than in those who had had a partial arthroscopic synovectomy (p = 0.01). PMID- 1463473 TI - Barriers to pediatric referral in managed care systems. AB - Anecdotal evidence suggests that children's access to pediatric subspecialty and inpatient care is hampered by referral barriers imposed by managed care systems. To identify such barriers and determine how they affect the referral process, a sample of American Academy of Pediatrics Fellows (n = 1598) was surveyed. The response rate was 79.1% (n = 1264). Of those pediatricians in direct patient care (n = 956), 71.4% participated in a managed care plan. Pediatricians referred patients in managed care systems somewhat less frequently than in traditional pay systems: 8.7% and 6.9% referred managed care patients to subspecialists and inpatient care, respectively, less often. More than 20% and 10% of pediatricians with patients in managed care systems had at least one referral to subspecialist care and inpatient care, respectively, denied in the previous year. Pediatricians experienced more barriers in preferred provider organizations than in health maintenance organizations. These data suggest that utilization management programs, such as those used in managed care systems, may limit necessary access to pediatric subspecialty and inpatient care. PMID- 1463474 TI - Dengue. PMID- 1463475 TI - The case for using waist to hip ratio measurements in routine medical checks. AB - OBJECTIVE: To provide a rationale for using waist:hip ratio (WHR) measurements in clinical practice. DATA SOURCES: The article reviews the literature on body fat distribution back to the mid 1950s. STUDY SELECTION: Studies are reviewed which show a clear association between abdominal obesity and a range of ailments including coronary events, hypertension, blood lipid levels, cholecystectomy, diabetes and gallbladder disease. DATA EXTRACTION: Key data on the correlation of body fat distribution and health risks are summarised. DATA SYNTHESIS: Abdominal fat measured by a WHR may be a better single predictor of many diseases than other risk factors such as overall obesity, hypertension, smoking, or hypercholesterolaemia. CONCLUSIONS: The association between WHR and risk indicators appears to be "dose" related, and independent of sex, race and age. High WHRs, however, are more characteristic of men with lower socioeconomic status, whereas weight control programs are more commonly developed for women. A reorientation of weight control initiatives based on health rather than aesthetic priorities is needed. Measurement of WHR should be a routine part of clinical assessments. The predictability of the measure can be improved by combining it with a measure of body mass. PMID- 1463476 TI - Should radiologists report on every film? PMID- 1463477 TI - Caring for HIV-infected women and children. PMID- 1463478 TI - The appropriate goals of antihypertensive therapy: neither too much nor too little. AB - Although the treatment of hypertension has increased markedly during the last decade, many patients have been left undertreated, including many of the disadvantaged, the elderly, and those at relatively high overall risk for cardiovascular disease. A rapidly growing number of patients, however, are being exposed to overtreatment with resultant interference with their quality of life and potential hazards to their health. These include patients who are diagnosed and treated without adequate documentation of the presence of persistent hypertension, patients who are not appropriately managed with nondrug therapies, and patients who are given inappropriate and overly aggressive drug therapies. Better recognition of the frequency and potential hazards of overtreatment is needed so that more appropriate goals of antihypertensive therapy can be established and maintained. PMID- 1463479 TI - Treating depression and anxiety in primary care. Closing the gap between knowledge and practice. PMID- 1463480 TI - Genomic structure and mapping of the chromosomal gene for transcobalamin I (TCN1): comparison to human intrinsic factor. AB - Transcobalamin I (TCI) is a vitamin B12 binding protein that is found in the secondary granules of mature neutrophils. The expression of the gene for TCI (TCN1) within neutrophils has been shown to be restricted to the later stages of myeloid development and can therefore be used as a marker for granulocyte differentiation. To study transcriptional control regions important in late stage myeloid gene regulation the genomic sequence for TCN1 has been cloned. Clones were isolated from a genomic library constructed in Charon 4A using homologous full-length cDNA probes. Southern blot analysis showed the gene to reside on five EcoRI fragments totaling 14 kb in length. Two overlapping phage clones, containing the entire 14 kb, were isolated and the introns and exons were mapped using Southern blotting and dideoxy sequencing of subclones. The cDNA is represented by nine exons contained within 12 kb of genomic DNA. Comparison of the genomic structure to gastric intrinsic factor (GIF), another vitamin B12 binding protein, revealed a strikingly similar intron/exon structure, with several positionally conserved splice sites. The gene was localized to chromosome 11 using in situ hybridization. PMID- 1463481 TI - NSAID adverse effects & interactions: who is at risk? PMID- 1463482 TI - Can physicians afford not to get involved in hospital administration? PMID- 1463483 TI - Add another dose of Haemophilus influenzae vaccine.